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BACKGROUND: Although previous studies have demonstrated that tumor deposits (TDs) are associated with worse prognosis in colon cancer, their clinical significance in rectal cancer has not been fully elucidated, especially in the lateral pelvic lymph node (LPLN) area. This study aimed to clarify the clinical significance of TDs, focusing on the number of metastatic foci, including lymph node metastases (LNMs) and TDs, in the LPLN area. METHODS: This retrospective study involved 226 consecutive patients with cStage II/III low rectal cancer who underwent LPLN dissection. Metastatic foci, including LNM and TD, in the LPLN area were defined as lateral pelvic metastases (LP-M) and were evaluated according to LP-M status: presence (absence vs. presence), histopathological classification (LNM vs. TD), and number (one to three vs. four or more). We evaluated the relapse-free survival of each model and compared them using the Akaike information criterion (AIC) and Harrell's concordance index (c-index). RESULTS: Forty-nine of 226 patients (22%) had LP-M, and 15 patients (7%) had TDs. The median number of LP-M per patient was one (range, 1-9). The best risk stratification power was observed for number (AIC, 758; c-index, 0.668) compared with presence (AIC, 759; c-index, 0.665) and histopathological classification (AIC, 761; c-index, 0.664). The number of LP-M was an independent prognostic factor for both relapse-free and overall survival, and was significantly associated with cumulative local recurrence. CONCLUSION: The number of metastatic foci, including LNMs and TDs, in the LPLN area is useful for risk stratification of patients with low rectal cancer.

DOI： 10.1007/s10147-023-02391-1

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DOI： 10.1245/s10434-023-13418-2

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DOI： 10.1245/s10434-023-13440-4

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BACKGROUND: Next-generation sequencing (NGS) has enabled comprehensive genomic profiling to identify gene alterations that play important roles in cancer biology. However, the clinical significance of these genomic alterations in triple-negative breast cancer (TNBC) patients has not yet been fully elucidated. The aim of this study was to clarify the clinical significance of genomic profiling data, including copy number alterations (CNA) and tumor mutation burden (TMB), in TNBC patients. METHODS: A total of 47 patients with Stage I-III TNBC with genomic profiling of 435 known cancer genes by NGS were enrolled in this study. Disease-free survival (DFS) and overall survival (OS) were evaluated for their association to gene profiling data. RESULTS: CNA-high patients showed significantly worse DFS and OS than CNA-low patients (p = 0.0009, p = 0.0041, respectively). TMB was not associated with DFS or OS in TNBC patients. Patients with TP53 alterations showed a tendency of worse DFS (p = 0.0953) and significantly worse OS (p = 0.0338) compared with patients without TP53 alterations. Multivariable analysis including CNA and other clinicopathological parameters revealed that CNA was an independent prognostic factor for DFS (p = 0.0104) and OS (p = 0.0306). Finally, multivariable analysis also revealed the combination of CNA-high and TP53 alterations is an independent prognostic factor for DFS (p = 0.0005) and OS (p = 0.0023). CONCLUSIONS: We revealed that CNA, but not TMB, is significantly associated with DFS and OS in TNBC patients. The combination of CNA-high and TP53 alterations may be a promising biomarker that can inform beyond standard clinicopathologic factors to identify a subgroup of TNBC patients with significantly worse prognosis.

DOI： 10.1007/s12282-023-01449-2

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BACKGROUND: The definition and classification of regional nodes are not standardized for perihilar cholangiocarcinoma. This study aimed to clarify the rational extent of regional lymphadenectomy and to elucidate the impact of number-based regional nodal classification on survival of patients with this disease. METHODS: Data of 136 patients with perihilar cholangiocarcinoma who underwent surgery were reviewed. The incidence of metastasis and the survival of patients with metastasis were calculated for each node group. RESULTS: The incidence of metastasis for the node groups in the hepatoduodenal ligament (denoted as no. 12) ranged from 3.7% to 25.4%, with 5-year disease-specific survival of 12.9% to 33.3% for patients with metastasis. The incidences of metastasis in the common hepatic artery (no. 8) and posterior superior pancreaticoduodenal (no. 13a) node groups were 14.4% and 11.2%, respectively, with 5-year disease-specific survival rates of 16.7% and 20.0% for the patients with metastasis. When these node groups were defined as regional nodes, the 5-year disease-specific survival rates for the patients with pN0 (n = 80), pN1 (1-3 positive nodes, n = 38), and pN2 (≥ 4 positive nodes, n = 18) were 61.4%, 22.9%, and 17.6%, respectively (p < 0.001). The pN classification was independently associated with disease-specific survival (p < 0.001). When only the no. 12 node groups were regarded as regional nodes, pN classification failed to stratify the patients prognostically. CONCLUSIONS: No. 8 and no. 13a node groups should be considered regional nodes in addition to no. 12 node groups and should be dissected. The number-based regional nodal classification allows patients with this disease to be stratified prognostically.

DOI： 10.1245/s10434-023-13361-2

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Language：Japanese   Publisher：(一社)日本乳癌学会  

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BACKGROUND: This study aimed to clarify potential candidates for anatomic resection (AR) among patients with pathological T1-T2 (pT1-T2) hepatocellular carcinoma (HCC) and to determine whether AR is effective for HCC with microscopic vascular invasion (MVI). METHODS: We retrospectively analyzed 288 patients with pT1a (n = 50), pT1b (n = 134) or pT2 (n = 104) HCC who underwent curative-intent resection between 1990 and 2010. Surgical outcomes were compared between patients who underwent AR (n = 189) and those who underwent nonanatomic resection (NAR; n = 99) according to pT category and MVI status. RESULTS: Patients who underwent AR were more likely to have good hepatic functional reserve and an aggressive primary tumor than those who underwent NAR. When patients were stratified according to pT category, AR had a more favorable impact on survival than NAR only in patients with pT2 HCC in univariate (5-year survival, 51.5% vs. 34.6%; p = 0.010) and multivariate analysis (hazard ratio 0.505; p = 0.014). However, AR had no impact on survival in patients with pT1a or pT1b HCC. In patients with MVI (n = 57), AR achieved better survival than NAR (5-year survival, 52.0% vs. 16.7%; p = 0.019) and was an independent prognostic factor (hazard ratio 0.335; p = 0.020). In patients without MVI (n = 231), there was no significant difference in survival between the two groups (p = 0.221). CONCLUSION: AR was identified as an independent factor in improved survival in patients with pT2 HCC or HCC with MVI.

DOI： 10.1016/j.suronc.2023.101951

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INTRODUCTION: Colorectal cancer (CRC) is one of the major life-threatening complications in patients with Crohn's disease (CD). Previous studies of CD-associated CRC (CD-CRC) have involved only small numbers of patients, and no large series have been reported from Asia. The aim of this study was to clarify the prognosis and clinicopathological features of CD-CRC compared with sporadic CRC. METHODS: A large nationwide database was used to identify patients with CD-CRC (n = 233) and sporadic CRC (n = 129,783) over a 40-year period, from 1980 to 2020. Five-year overall survival (OS), recurrence-free survival (RFS), and clinicopathological characteristics were investigated. The prognosis of CD-CRC was further evaluated in groups divided by colon cancer and anorectal cancer (RC). Multivariable Cox regression analysis was used to adjust for confounding by unbalanced covariables. RESULTS: Compared with sporadic cases, patients with CD-CRC were younger; more often had RC, multiple lesions, and mucinous adenocarcinoma; and had lower R0 resection rates. Five-year OS was worse for CD-CRC than for sporadic CRC (53.99% vs 71.17%, P < 0.001). Multivariable Cox regression analysis revealed that CD was associated with significantly poorer survival (hazard ratio 2.36, 95% confidence interval: 1.54-3.62, P < 0.0001). Evaluation by tumor location showed significantly worse 5-year OS and RFS of CD-RC compared with sporadic RC. Recurrence was identified in 39.57% of CD-RC cases and was mostly local. DISCUSSION: Poor prognosis of CD-CRC is attributable primarily to RC and high local recurrence. Local control is indispensable to improving prognosis.

DOI： 10.14309/ajg.0000000000002269

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本腹部救急医学会  

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INTRODUCTION: This study aimed to evaluate the association between the preoperative Controlling Nutritional Status (CONUT) score, survival outcomes, and recurrence pattern in patients with resectable biliary tract cancer (BTC). METHODS: A total of 224 BTC patients (gallbladder, n = 69; intrahepatic bile ducts, n = 26; perihilar bile ducts, n = 72; distal bile duct, n = 57) who underwent surgery with curative intent were enrolled. The best cutoff point of the preoperative CONUT score in discriminating survival was determined using χ2 scores. The sites of recurrence were subclassified as locoregional or distant. RESULTS: Patients were subdivided into the CONUT-low (score ≤ 3, n = 156) and the CONUT-high (score > 3; n = 68) groups. In-hospital mortality occurred more frequently in the CONUT-high group than in the CONUT-low group (7.4% vs. 1.3%; p = 0.028). A high preoperative CONUT score was independently associated with worse overall survival (hazard ratio [HR] 1.906, p = 0.001), worse disease-specific survival (HR 1.840, p = 0.006), and worse recurrence-free survival (HR 1.680, p = 0.005). Recurrence developed in 110 (49.1%) patients. A high preoperative CONUT score was independently associated with a higher risk of distant recurrence (HR 2.245, p = 0.001), but not locoregional recurrence. The incidences of distant recurrence at 5 years were 55.4% and 34.2% in the CONUT-high and CONUT-low groups, respectively (p = 0.001). CONCLUSIONS: The preoperative CONUT score independently predicts survival outcomes and may serve as a surrogate marker of aggressive systemic disease recurrence in patients with resectable BTC.

DOI： 10.1016/j.ejso.2022.11.003

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We report a case of intrahepatic cholangiocarcinoma(ICC)with lymph node metastases in which long-term survival was achieved after surgery followed by chemotherapy. A 69-year-old man underwent left hepatectomy, extrahepatic bile duct resection, and lymph node dissection for ICC located mainly in segment 4 of the liver with enlarged lymph nodes in the hepatoduodenal ligament. The histopathologically confirmed diagnosis was ICC(T2N1M0, Stage ⅣA)with 3 positive lymph nodes(No. 12a1, No. 12p1, and No. 12p2). He received chemotherapy with gemcitabine(GEM)plus cisplatin(CDDP)for 9 months, followed by GEM monotherapy for 4 months, and then S-1 monotherapy was started. A right lung nodule was detected 12 months after the initiation of S-1 monotherapy. He received GEM plus S-1 therapy for 28 months, followed by S-1 monotherapy, leading to disappearance of the lung nodule. He remains alive and well without disease 78 months after surgery. Our experience in this case suggests that radical resection followed by chemotherapy may provide a survival benefit in selected patients who have ICC with nodal disease.

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BACKGROUND: Anastomotic leakage (AL) is a serious complication after esophagectomy for esophageal cancer. The objective of this study was to identify the risk factors for AL. METHODS: Patients with esophageal cancer who underwent curative esophagectomy and cervical esophagogastric anastomosis between 2009 and 2019 (N = 346) and those between 2020 and 2022 (N = 17) were enrolled in the study to identify the risk factors for AL and the study to assess the association between the risk factors and blood flow in the gastric conduit evaluated by indocyanine green (ICG) fluorescence imaging, respectively. RESULTS: AL occurred in 17 out of 346 patients (4.9%). Peptic or endoscopic submucosal dissection (ESD) ulcer scars were independently associated with AL (OR 6.872, 95% CI 2.112-22.365) in addition to diabetes mellitus. The ulcer scars in the anterior/posterior gastric wall were more frequently observed in patients with AL than in those without AL (75.0% vs. 17.4%, P = 0.042). The median flow velocity of ICG fluorescence in the gastric conduits with the scars was significantly lower than in those without the scars (1.17 cm/s vs. 2.23 cm/s, P = 0.004). CONCLUSIONS: Peptic or ESD ulcer scarring is a risk factor for AL after esophagectomy in addition to diabetes mellitus. The scars in the anterior/posterior gastric wall are significantly associated with AL, impairing blood flow of the gastric conduit. Preventive interventions and careful postoperative management should be provided to minimize the risk and severity of AL in patients with these risk factors.

DOI： 10.1007/s11605-022-05545-0

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BACKGROUND: Patients with longstanding inflammatory bowel disease are at high risk of developing intestinal cancers. In this study, we aimed to elucidate the differences between intestinal cancers associated with ulcerative colitis and Crohn's disease. METHODS: Intestinal cancers in ulcerative colitis and Crohn's disease patients treated between 1983 and 2020 at 43 Japanese institutions were retrospectively analyzed.. RESULTS: A total of 1505 intestinal cancers in 1189 ulcerative colitis and 316 Crohn's disease patients were studied. Almost all of ulcerative colitis-associated cancers (99%) were in the colon and rectum, whereas half of Crohn's disease-associated cancers (44%) were in the anus, with 11% in the small intestine. Ulcerative colitis-associated cancers were diagnosed more frequently by surveillance (67% vs. 25%, P < 0.0001) and at earlier stages (stages 0-1, 71% vs. 27%, P < 0.0001) compared with Crohn's disease-associated cancers. Colorectal cancers associated with Crohn's disease showed a significantly worse 5-year overall survival rate than those associated with ulcerative colitis (stage 2, 76% vs. 89%, P = 0.01, stage 3, 18% vs. 68%, P = 0.0009, and stage 4, 0% vs. 13%, P = 0.04). Surveillance correlated with earlier diagnoses for ulcerative colitis- and Crohn's disease-associated intestinal cancers, whereas shorter intervals between endoscopic examinations correlated with an earlier cancer diagnosis in ulcerative colitis patients but not in Crohn's disease patients. CONCLUSIONS: The clinical and oncological features of ulcerative colitis- and Crohn's disease-associated cancers were very different. Crohn's disease-associated cancers were diagnosed at more advanced stages and were detected less frequently by surveillance. Additionally, they showed a significantly poorer prognosis.

DOI： 10.1007/s00535-022-01927-y

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BACKGROUND: Recent improvements in systemic chemotherapy have provided an opportunity for patients with stage IV gastric cancer (GC) to undergo conversion surgery (CS). The aim of this study was to evaluate the long-term outcomes of patients who underwent CS and to elucidate the prognostic factors for CS in stage IV GC. METHODS: A total of 79 patients who underwent CS with the aim of R0 resection for stage IV GC at six institutions from January 2008 to July 2019 were enrolled. We retrospectively reviewed the clinicopathological data and prognosis. RESULTS: Of the 79 patients, 23 (31.1%) had initially resectable disease (IR) before chemotherapy, defined as positive for cancer on peritoneal cytology (CY1), resectable hepatic metastasis, or para-aortic lymph node No. 16a2/b1 metastasis. Of the 56 remaining patients with primary unresectable disease, 39 had peritoneal dissemination. R0 resection was accomplished in 63 patients (79.7%). The 3-year OS rates for patients with IR and unresectable disease were 78.3% and 44.5%, respectively. Multivariate analysis showed that IR (P = 0.014) and R0 (P = 0.014) were statistically significant independent prognostic factors for favorable OS. Among patients with peritoneal dissemination alone, OS was significantly better for patients with R0 resection than for patients with R1/2 resection, with the 3-year OS rates of 65.5% and 23.1%, respectively (P = 0.011). CONCLUSIONS: CS is a treatment option for selected patients with stage IV GC. Patients with IR and patients who achieve R0 resection may obtain a survival benefit from CS.

DOI： 10.1186/s12893-022-01874-8

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The patient was a 71-year-old man with a diagnosis of duodenal carcinoma. Abdominal computed tomography(CT) showed no distant metastasis, and he underwent subtotal stomach-preserving pancreaticoduodenectomy. Postoperative adjuvant chemotherapy was not administered. A left supraclavicular lymph node recurrence was detected on CT 15 months after surgery. Capecitabine and oxaliplatin(CAPOX)therapy was administered and the metastatic lesion shrank. Positron emission tomography(PET)-CT showed no lesions at other sites and left cervical lymph node dissection was performed 5 months after the recurrence. Postoperative adjuvant therapy with S-1 was administered for 6 months. However, 2 years and 10 months after the first recurrence, CT showed recurrence in the left supraclavicular lymph node. CAPOX therapy was resumed, but due to an allergic reaction to oxaliplatin, the patient was treated with capecitabine alone. The recurrent lesion was gradually increased in size, and FOLFIRI therapy was introduced. One year and 5 months after secondary recurrence, PET-CT showed that the second recurrent lesion had grown but was confined to the left supraclavicular lymph node, so radiation therapy(60 Gy)to the left neck was performed. The disease was stable for about 10 months and chemotherapy could be discontinued. The lesion increased in size thereafter, and the patient died 7 years after initial surgery.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elmer Press, Inc.  

BACKGROUND: Severe neutropenia, including febrile neutropenia, is a major toxicity of systemic chemotherapy that leads to delays in treatment, higher costs, and mortality. Severe neutropenia may occur during neoadjuvant chemotherapy even when the patients are free from known risk factors. Pegfilgrastim, a covalent conjugant of filgrastim that stimulate the production of neutrophils, is used for prevention. The current study aimed to reveal the characteristics of patients who need pegfilgrastim for primary prophylaxis to prevent severe neutropenia, including febrile neutropenia and grade 3 neutropenia, during neoadjuvant chemotherapy. METHODS: A retrospective analysis of 83 patients treated with neoadjuvant adriamycin/cyclophosphamide followed by docetaxel chemotherapy was performed. The factors which associated with severe neutropenia were examined by univariate and multivariate analyses. RESULTS: Severe neutropenia developed in one of 22 patients (5%) with pegfilgrastim for primary prophylaxis and in 17 of 61 patients (28%) without it. In 83 patients, the incidence of severe neutropenia was significantly decreased in the patients with pegfilgrastim for primary prophylaxis shown by the univariate analysis (P = 0.023) and multivariate analysis (P = 0.030). In 61 patients without pegfilgrastim for primary prophylaxis, the univariate analysis showed that severe neutropenia was associated with tumor size (P = 0.004), clinical stage (P = 0.009), and cancer antigen 15-3 (CA15-3) (P = 0.026). The multivariate analysis showed that clinical stage was associated with severe neutropenia (P = 0.021). CONCLUSIONS: The current study demonstrated that advanced stage is a risk for severe neutropenia in patients treated with neoadjuvant adriamycin/cyclophosphamide followed by docetaxel chemotherapy. Given that prophylaxis with pegfilgrastim was associated with significantly lower incidence of severe neutropenia, patient with advance stage breast cancer may benefit from pegfilgrastim during neoadjuvant chemotherapy.

DOI： 10.14740/wjon1530

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A 53-year-old woman underwent subtotal stomach-preserving pancreaticoduodenectomy(SSPPD)for resectable pancreatic cancer after neoadjuvant chemotherapy. Postoperatively, she received hepatic arterial infusion of 5-FU and S-1 chemotherapy. Two years after SSPPD, abdominal computed tomography showed a 2-cm mass in the remnant pancreas, which was diagnosed as recurrence of cancer by endoscopic ultrasound-guided fine-needle aspiration. Staging laparoscopy was performed and peritoneal washing cytology(CY)was positive. She then received gemcitabine plus nab-paclitaxel chemotherapy for 8 months. After that, staging laparoscopy was performed again and negative CY was confirmed. A total remnant pancreatectomy with splenectomy was performed. She received chemotherapy after pancreatectomy and is now alive and well without recurrence 2 years and 1 month after the second surgery. Although positive CY is a poor prognostic factor, surgery combined with perioperative chemotherapy may contribute to prolonged survival for some patients who have recurrence in the remnant pancreas with positive CY.

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A 71-year-old man with middle thoracic esophageal cancer was treated with neoadjuvant chemotherapy using docetaxel plus 5-FU plus cisplatin therapy and was also administered pegfilgrastim. Blood tests showed elevated white blood cell counts and C-reactive protein levels before the start of the third course. Contrast-enhanced computed tomography revealed wall thickening of the aortic arch. We diagnosed this as aortitis due to pegfilgrastim. Inflammation was improved with conservative treatment. We then performed video-assisted thoracoscopic esophagectomy. Drug-induced vasculitis should be included in the differential diagnosis of patients with elevated inflammation markers of unknown cause following the administration of granulocyte colony-stimulating factor preparations.

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Neurenteric cyst (NC) shows benign histopathology and rarely demonstrate malignant transformation. We herein describe a case of NC that exhibited malignant transformation. A 65-year-old female presented with gait disturbance due to compression by a cystic mass on the dorsal surface of the medulla oblongata. Partial resection was performed twice, leading to improvement of her symptoms. Two years after the second surgery, gadolinium-perfused T1-weighted magnetic resonance imaging revealed an invasive lesion with contrast enhancement at the trigone of the left lateral ventricle for which partial resection followed by radiotherapy was performed. However, mass regrowth was observed, with the patient eventually succumbing to her disease 11 months after her third surgery. Histopathological analyses of the first and second surgical specimens identified pseudostratified cuboidal epithelial cells, with no nuclear or cellular atypia resembling gastrointestinal mucosa, lining the inner surface of the cystic wall. Based on these findings the lesion was diagnosed as NC. The third surgical specimen exhibited apparent malignant features of the epithelial cells with elongated and hyperchromatic nuclei, several mitotic figures, small necrotic foci, and a patternless or sheet-like arrangement. Based on these findings, the lesion was diagnosed as NC with malignant transformation. Next-generation sequencing revealed KRAS p.G12D mutation in all specimens. Additionally, the third surgical specimen harbored the following 12 de novo gene alterations: ARID1A loss, BAP1 p.F170L, CDKN1B loss, CDKN2A loss, CDKN2B loss, FLCN loss, PTCH1 loss, PTEN loss, PTPRD loss, SUFU loss, TP53 loss, and TSC1 loss. The aforementioned results suggest that KRAS mutation is associated with the development of the NC, and that the additional gene alterations contribute to malignant transformation of the NC.

DOI： 10.1111/neup.12822

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A 74-year-old man presented to our hospital with a mass in the left supraclavicular fossa. He was diagnosed with advanced gastric cancer with liver metastasis and left supraclavicular and para-aortic lymph node metastasis, cT3N2M1 (LYM, HEP), cStage Ⅳ(the Union for International Cancer Control, TNM 7th edition). He received a total of 3 courses of S- 1 plus cisplatin therapy. Since he developed adverse reactions such as anorexia, renal dysfunction, and thrombocytopenia and the tumor was HER2-positive, he received 25 courses of capecitabine, cisplatin, and trastuzumab chemotherapy. Three years and 2 months after the first chemotherapy, remarkable tumor reduction was observed. The patient then underwent radical distal gastrectomy with D2 lymphadenectomy, and R0 resection was achieved. The histopathological diagnosis was ypT1aN0M0, ypStage ⅠA. Chemotherapy with trastuzumab may improve the long-term prognosis of HER2-positive Stage Ⅳ gastric cancer if the disease is controlled and radical resection can be achieved.

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A woman in her 60s had been aware of perianal erosions for 1 month. Skin biopsy showed Paget's cells in the stratified squamous epithelium, and immunohistochemistry showed negative staining for CK7 and positive staining for CK20. Colonoscopy revealed well-differentiated adenocarcinoma in the anal canal. Computed tomography showed neither regional lymph node metastasis nor distant metastasis. Hence, she was diagnosed with anal canal carcinoma with pagetoid spread. We determined the extent of resection of the skin lesion preoperatively by mapping biopsy, and performed laparoscopic abdominoperineal resection. The pathological findings revealed adenocarcinoma(tub1, tub2), and the skin resection margin was negative. Immunohistochemistry for Paget's cells in the stratified squamous epithelium showed negative staining for GCDFP-15 and CK7, and positive staining for CK20. Twenty-four months after surgery, we detected right inguinal lymph node metastasis and performed right inguinal lymphadenectomy. As of 4 months after the lymphadenectomy, no local recurrence or distant metastasis has been detected during follow-up examinations.

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Ulcerative colitis-associated neoplasia (UCAN) harbors unique genetic alterations and mutational tendencies. The clinical application of gene panel testing enables precision medicine by tailoring treatment to individual gene alterations. We hypothesized that gene panel testing may detect clinically important genetic alterations in UCAN, with potential usefulness for the diagnosis and treatment of UCAN. In the present study, gene panel testing was used to identify genetic alterations in UCAN, and the possibility of clinical utility of gene panel testing in UCAN was investigated. The present study included 15 patients with UCAN, and gene panel testing was performed to identify genetic alterations associated with diagnosis and treatment. Genetic alterations of UCAN were compared with those of 203 patients with sporadic colorectal cancer (CRC). APC and PTEN mutations were less frequent, while RNF43 frameshift or nonsense mutations were more frequent in UCAN compared with sporadic CRC. TP53 mutations were identified in 13/15 patients (87%) with UCAN. Notably, 4/15 patients (27%) with UCAN had no genetic alterations other than TP53 mutation, while this occurred in 1/203 patients (0.5%) with sporadic CRC (P<0.001). Microsatellite instability-high was identified in 2/15 patients (13%) with UCAN. Mutational signature 3, which is associated with homologous recombination deficiency, was detected in 14/15 patients (93%) with UCAN, and enriched in UCAN compared with sporadic CRC (P=0.030). In conclusion, gene panel testing can detect important genetic alterations that can be useful for diagnosis and treatment in UCAN, and may provide clinicians with important information for tailored treatment strategies.

DOI： 10.3892/ol.2022.13562

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The outer mucus layer of the colorectal epithelium is easily removable and colonized by commensal microbiota, while the inner mucus layer is firmly attached to the epithelium and devoid of bacteria. Although the specific bacteria penetrating the inner mucus layer can contact epithelial cells and trigger cancer development, most studies ignore the degree of mucus adhesion at sampling. Therefore, we evaluated whether bacteria adhering to tissues could be identified by removing the outer mucus layer. Our 16S rRNA gene sequencing analysis of 18 surgical specimens of human colorectal cancer revealed that Sutterella (P = 0.045) and Enterobacteriaceae (P = 0.045) were significantly enriched in the mucus covering the mucosa relative to the mucosa. Rikenellaceae (P = 0.026) was significantly enriched in the mucus covering cancer tissues compared with those same cancer tissues. Ruminococcaceae (P = 0.015), Enterobacteriaceae (P = 0.030), and Erysipelotrichaceae (P = 0.028) were significantly enriched in the mucus covering the mucosa compared with the mucus covering cancers. Fusobacterium (P = 0.038) was significantly enriched in the mucus covering cancers compared with the mucus covering the mucosa. Comparing the microbiomes of mucus and tissues with mucus removed may facilitate identifying bacteria that genuinely invade tissues and affect tumorigenesis.

DOI： 10.1038/s41598-022-21928-4

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Gastric cancer is a Lynch syndrome (LS)-associated tumor, with the cumulative lifetime risk in LS patients estimated to be 5.8-13%. Hence, surveillance for gastric cancer is important for LS patients, especially in those with a family history of gastric cancer or of Asian descent. We report a very rare case of a LS patient who showed gastric metastasis from jejunal adenocarcinoma curatively resected 8 years prior. A 79-year-old female was diagnosed with a synchronous gastric submucosal tumor (SMT) and right-sided colon cancer. She was referred to our hospital as she and her family had histories of LS-associated tumors. She underwent curative intent surgery for the tumors. Postoperative histopathological examination revealed the gastric SMT was an adenocarcinoma completely covered by non-neoplastic gastric mucosa. Immunohistochemical analyses showed the gastric SMT had the same expression pattern for CDX2, cytokeratins 7 and 20 as the jejunal adenocarcinoma. Thirty-four months after surgery the patient is alive without recurrence or any other LS-associated tumors. To the best of our knowledge, this is the first report of gastric metastasis from small bowel adenocarcinoma in a LS patient. Awareness of this case may be important for gastric cancer surveillance in LS patients.

DOI： 10.1007/s12328-022-01625-5

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Language：Japanese   Publisher：(一社)日本遺伝カウンセリング学会  

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With the discovery of bacterial symbiosis in the tissues of various cancers, the study of the tumor microbiome is attracting a great deal of attention. Anatomically, since the gastrointestinal tract, liver, and pancreas form a continuous ductal structure, the microbiomes in the digestive juices of these organs may influence each other. Here, we report a series of microbiome data in tumor-associated tissues such as tumor, non-tumor, and lymph nodes, and body fluids such as saliva, gastric juice, pancreatic juice, bile, and feces of patients with pancreatic or biliary tract cancers. The results show that the microbiome of tumor-associated tissues has a very similar bacterial composition, but that in body fluids has different bacterial composition which varies by location, where some bacteria localize to specific body fluids. Surprisingly, Akkermansia was only detected in the bile of patients with biliary tract cancer and its presence was significantly associated with the performance of external biliary drainage (P = 0.041). Furthermore, we found that tumor-associated tissues and body fluids in deep inner body are mostly inhabited by unidentified and uncharacterized bacteria, suggesting that such bacteria may be potential targets for precision therapy in the future.

DOI： 10.1038/s41598-022-12658-8

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Language：Japanese   Publisher：新潟医学会  

【目的】消化器外科術後に発症した播種性血管内凝固(disseminated intravascular coagulation;以下,DICと略記)に対する遺伝子組み換えトロンボモジュリン(recombinant human soluble thrombomodulin;以下,rTMと略記)の効果を検証し,治療成績改善に向けた方策を考察する.【方法】2016年1月から2021年5月に当科で消化器外科術後DICの改善を目的にrTMが投与された48例を対象とした.対象症例におけるDICの改善効果,および在院死亡の危険因子を検証した.DICの診断には,日本救急医学会の急性期DIC診断基準を使用した.患者背景および検査項目に関する2群間のカテゴリー変数の比較にはPearsonのχ2検定,Fisherの直接法を用いた.多変量解析はstepwise法によるロジスティック回帰分析を用いて行った.生存曲線はKaplan-Meier法で算出し,log rank検定で有意差検定を行った.有意水準5%(P<0.05)をもって有意差ありと判断した.【結果】年齢の中央値は76歳(59-91),男女比は21:27であった.原疾患は下部消化管穿孔が22例(45.8%),悪性腫瘍が11例(22.9%),消化管虚血が10例(20.8%),上部消化管穿孔が5例(10.4%)であった.DICを発症した原因は,急性汎発性腹膜炎が38例(79.2%),術後感染症が5例(10.4%),術後肝不全が4例(8.3%),術後出血が1例(2.1%)であった.rTM投与開始後7日目に28例(58.3%)で血小板数増加を認め,31例(64.6%)でDICスコアの改善を認めた.投与開始後28日の生存率は72.9%で,在院死亡率は41.7%であった.在院死亡群と生存群における比較では,在院死亡群において「悪性疾患あり」(P=0.034),「DICの原因が術後肝不全」(P=0.025),rTM投与開始時の「血小板数5万/μl未満」(P=0.009),「総ビリルビン2.0mg/dl以上」(P=0.002),rTM投与開始後7日目の「血小板数増加なし」(P=0.001),「DICスコア改善なし」(P=0.003)の占める割合が高かった.多変量解析ではrTM投与開始後7日目の「血小板数増加なし」(HR 5.076:95%CI 1.145-22.222:P=0.032)が独立した在院死亡の危険因子であった.【結語】消化器外科術後に発症するDICは極めて予後不良な病態であるが,rTM投与開始後早期に血小板数の増加を認めた場合,予後の改善を期待できる可能性がある.(著者抄録)

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Gastrointestinal duplications are congenital malformations that are usually observed in pediatric patients. Diagnosis in adulthood is quite rare, and preoperative diagnosis of gastrointestinal duplication is difficult, particularly in the small intestine. We encountered an extremely rare adult case of duplication of the jejunum, which showed a stomach-like form diagnosed using double-balloon enteroscopy (DBE). The patient was an 18-year-old male who had been experiencing upper abdominal pain and vomiting repeatedly without any triggers for 3 years. Various examinations were performed, but no cause of symptoms was found. DBE revealed a narrow opening of the lumen at the upper jejunum, and the lumen was covered with mucosal folds similar to those of the stomach. Enteroclysis via DBE showed a tubular structure on the mesenteric side of the jejunum. We diagnosed a jejunal tubular duplication with ectopic gastric mucosa and underwent partial small bowel resection. The patient's abdominal symptoms resolved. From this, DBE can be a useful tool for diagnosing intestinal duplication in adults. We believe that this case and literature review will facilitate the accurate and prompt diagnosis of small intestinal duplication.

DOI： 10.1007/s12328-022-01596-7

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OBJECTIVES: Diversion colitis (DC) is an inflammatory disorder caused by interruption of the fecal stream and subsequent nutrient deficiency from luminal bacteria. The utility of fecal microbiota transplantation (FMT) for DC was recently investigated; however, the precise pathogenesis of this condition remains unclear. This study aimed to evaluate the utility of autologous FMT in DC and to determine the related changes in the intestinal microbiota. METHODS: Autologous FMT was performed to reestablish the intestinal microbiota in five patients (average age, 64.6 ± 8.3 years) with DC. They underwent double-ended colostomy. We assessed the diverted colon by endoscopy and evaluated the microbiota before and after FMT using the 16S rRNA gene sequencing method. RESULTS: All five patients had mild inflammation (ulcerative colitis endoscopic index of severity [UCEIS] 2-3) in the diverted colon based on the colonoscopic findings. Three patients presented with symptoms, such as tenesmus, mucoid stool, and bloody stool. With FMT treatment, all patients achieved endoscopic remission (UCEIS score of 0 or 1) and symptomatic improvement. We observed a significantly decreased α-diversity in DC patients compared to healthy controls. The frequency of aerobic bacteria, such as Enterobacteriaceae, in the diverted colon decreased after autologous FMT. CONCLUSIONS: This study was the first to show that the microbiota in the diverted colon was significantly affected by autologous FMT. Since interruption of the fecal stream is central to the development of DC, FMT can be considered a promising treatment.

DOI： 10.1002/deo2.63

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Neuroendocrine neoplasms of the colon and rectum are colorectal epithelial neoplasms with neuroendocrine differentiation. A platinum regimen used for small cell lung cancer is the currently recommended chemotherapy for gastroenteropancreatic neuroendocrine carcinomas (GEP-NECs), regardless of the organ. The BRAF V600E mutation has been recently reported as a druggable driver mutation in colorectal NECs. In BRAF V600E mutant colorectal cancer, a combination of BRAF inhibitor and anti-epidermal growth factor receptor (EGFR) antibody, with or without a MEK inhibitor, is recommended. Here, we report the case of 77-year-old man who had lymph node recurrence after surgery for primary ascending colonic NEC. Two cytotoxic regimens, cisplatin plus irinotecan and modified FOLFOX6, were administered as first- and second-line chemotherapies with no remarkable response observed. At this point, genetic analysis confirmed the tumor harbored a BRAF V600E mutation. Thus, a regimen of BRAF inhibitor plus anti-EGFR antibody was administered. After commencing this regimen, carcinoembryonic antigen levels decreased within normal range, and there was dramatic shrinkage of the lymph node metastases observed by chest and abdominal computed tomography scans. To our knowledge, this is the first reported case of a colorectal NEC responding to a BRAF inhibitor and anti-EGFR antibody.

DOI： 10.1007/s12328-022-01599-4

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DOI： 10.1007/s00595-022-02466-y

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BACKGROUND: ARID1A is a component of the SWI/SNF complex, which controls the accessibility of proteins to DNA. ARID1A mutations are frequently observed in colorectal cancers (CRCs) and have been reported to be associated with high mutational burden and tumor PD-L1 expression in vitro. AIM: To clarify the role of ARID1A mutation in CRC. METHOD AND RESULTS: We used next generation sequencing (NGS) and immunohistochemistry on clinically obtained samples. A total of 201 CRC tissues from Niigata University and Niigata Center Hospital were processed by NGS using the CANCERPLEX panel. Immunohistochemistry for ARID1A, PD-L1, MLH1, and MSH2 was performed on 66 propensity-matched (33 microsatellite instability-high [MSI-H] and 33 microsatellite-stable [MSS]) cases among 499 cases from Kyushu University. TCGA data were downloaded from cBioPortal. NGS showed significantly more mutations in ARID1A mutated CRCs (p = 0.01), and the trend was stronger for right-sided CRCs than left-sided. TCGA data confirmed these findings (p < 0.01). BRAF V600E and ATM mutations were also found at higher frequencies. Immunohistochemistry showed that 30% of MSI-H CRCs had ARID1A loss, while this was true in only 6% of MSS CRCs. In both MSI-H and MSS, PD-L1 expression by stromal cells was enhanced in the ARID1A-mutant groups (90% vs 39% in MSI-H, 100% vs 26% in MSS). CONCLUSION: We found a higher mutational burden in ARID1A-mutant CRCs, and IHC study showed that ARID1A loss was correlated with high PD-L1 expression in stromal cells regardless of MSI status. These data support the idea that mutant ARID1A is a potential biomarker for CRCs.

DOI： 10.1002/cnr2.1420

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Although numerous experiments revealed an essential role of a lipid mediator, sphingosine-1-phosphate (S1P), in breast cancer (BC) progression, the clinical significance of S1P remains unclear due to the difficulty of measuring lipids in patients. The aim of this study was to determine the plasma concentration of S1P in estrogen receptor (ER)-positive BC patients, as well as to investigate its clinical significance. We further explored the possibility of a treatment strategy targeting S1P in ER-positive BC patients by examining the effect of FTY720, a functional antagonist of S1P receptors, on hormone therapy-resistant cells. Plasma S1P levels were significantly higher in patients negative for progesterone receptor (PgR) expression than in those positive for expression (p = 0.003). Plasma S1P levels were also significantly higher in patients with larger tumor size (p = 0.012), lymph node metastasis (p = 0.014), and advanced cancer stage (p = 0.003), suggesting that higher levels of plasma S1P are associated with cancer progression. FTY720 suppressed the viability of not only wildtype MCF-7 cells, but also hormone therapy-resistant MCF-7 cells. Targeting S1P signaling in ER-positive BC appears to be a possible new treatment strategy, even for hormone therapy-resistant patients.

DOI： 10.3390/ijms222413367

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Language：Japanese   Publisher：(株)癌と化学療法社  

症例は72歳、男性。肛門痛と排便困難を主訴に来院した。肛門管内に腫瘤を認め、生検で腺癌と診断された。胸腹骨盤部CT検査の結果、遠隔転移を認めず、肛門管癌、cT3N0M0、cStage IIaと診断された。術前化学放射線療法(chemoradiotherapy:CRT)(capecitabine併用、1.8Gy28回、50.4Gy)を施行した。術前CRT8週間後、骨盤部CT検査にて縮小率34%とPR判定であった。術前CRTから15週間後に腹腔鏡下腹会陰式直腸切断術を施行した。病理組織学的診断では、組織型はadenocarcinoma(muc、tub1)であり、肛門周囲皮膚と肛門管重層扁平上皮の境界相当部から直腸粘膜に連続する痔瘻様上皮嵌入部に癌の上皮内病変を認めた。周囲に粘液癌を主体とする浸潤癌を認め、痔瘻癌と診断された。術後12ヵ月となる現在まで無再発生存中である。(著者抄録)

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A 70-year-old female with liver metastases from gastrointestinal stromal tumor(GIST)that were found 3 months after partial gastrectomy for the primary GIST underwent Auchincloss operation for left breast cancer with ipsilateral axillary lymph node metastases. The diagnosis was microinvasive ductal cancer that was pT1miN1M0, pStage ⅡA, hormone receptor negative, and HER2 positive. Given the impact of this cancer on the prognosis of liver metastases of GIST, imatinib therapy, but not adjuvant chemotherapy, was started promptly for breast cancer after surgery. Four months after the surgery, left subclavian lymph node recurrence of breast cancer was found. Since the liver metastases of GIST had been stable, imatinib was discontinued, and paclitaxel and anti-HER2 therapy were administered. After confirming tolerability, imatinib was carefully added in combination. Because the lymph nodes shrank and liver metastases of GIST were stable, both anti-HER2 therapy and imatinib were continued. There are few reports of combined chemotherapy for synchronous double cancer, and we report our experience in which careful treatment was required.

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症例は70歳、女性。胃GIST術後3ヵ月目に左乳癌、腋窩リンパ節転移、GIST肝転移を認め、左乳癌に対し手術を施行した。病理組織学的結果はHER2陽性乳癌、pT1miN1M0、pStage IIAであった。予後規定因子はGIST肝転移と考え、イマチニブを開始した。乳癌術後4ヵ月目に乳癌左鎖骨下リンパ節再発を認めた。GIST肝転移の病勢は安定していたためイマチニブをいったん休薬し、パクリタキセル、抗HER2療法を開始した。忍容性を確認した後、慎重にイマチニブを併用した。リンパ節は著明に縮小し肝転移も増大を認めず、パクリタキセルを7コースで終了した。現在は抗HER2療法、イマチニブを継続中である。転移性の重複癌において両者に対する薬物療法を同時併用した報告は少なく、若干の考察を加えて報告する。(著者抄録)

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A 72-year-old man had a chief complaint of anal pain and difficulty in defecation. He was diagnosed with adenocarcinoma by biopsy from a tumor of the anal canal. A computed tomography scan revealed neither regional lymph node metastasis nor distant metastasis. Hence, he was diagnosed with cT3N0M0, cStage Ⅱa anal canal cancer. Preoperative capecitabine- based chemoradiotherapy(CRT)(50.4 Gy in 28 fractions of 1.8 Gy each)was implemented. Digital rectal examination and imaging evaluation 8 weeks after preoperative CRT revealed that the tumor had shrunk. Fifteen weeks after preoperative CRT, laparoscopic abdominoperineal resection was performed. The pathological findings showed mucinous adenocarcinoma associated with anal fistula. At present, 12 months after the operation, no local recurrence and distant metastasis has been detected under follow-up evaluations.

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A 62-year-old man was incidentally found to have a pancreatic tumor by CT. He was diagnosed with pancreatic cancer by EUS-FNAB. Gemcitabine(GEM)plus nab-paclitaxel(PTX)was started as neoadjuvant chemotherapy(NAC)for resectable pancreatic cancer. However, after the end of the second course, the tumor grew rapidly and invaded the stomach, so NAC was discontinued, and surgery was performed. The pathological diagnosis was anaplastic ductal carcinoma of the pleomorphic cell type, and the histological response was Grade 1a. Multiple liver metastases appeared during adjuvant chemotherapy with S-1, so GEM plus nab-PTX and modified FOLFIRINOX were administered, but the therapeutic response was poor, the patient died 9 months after surgery. Anaplastic carcinoma has a poor response to chemotherapy and may be included with cancers showing treatment resistance to NAC, as seen in our case. It is necessary to pay attention to anaplastic carcinoma during the course of NAC for pancreatic cancer.

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症例は64歳、男性。慢性腎臓病で当院通院中に腹部CTで膵頭部癌と診断された。腹部CTおよびMRIでは遠隔転移や大動脈周囲リンパ節(PALN)転移は認めなかった。手術の方針とし術中にPALNサンプリングを行ったところ、迅速病理診断にてリンパ節4個中2個に転移を認めた。非切除とした場合、腎機能障害のため標準的な化学療法を施行できないと考え、PALN郭清を伴う亜全胃温存膵頭十二指腸切除術を施行した。病理診断は浸潤性膵管癌であり、S-1による術後補助化学療法を減量して行った。術後1年10ヵ月で腸間膜内リンパ節再発および肺転移再発を認めた。さらに、術後2年で腹腔内再発による上腸間膜動静脈狭窄を認めた。腹腔内再発に対し放射線療法を行い、引き続きgemcitabine単独療法を行った。肝外門脈狭窄による腹水貯留や消化管出血は治療により軽快した。結果、術後5年7ヵ月の長期生存を得た。(著者抄録)

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症例は64歳、男性。慢性腎臓病で当院通院中に腹部CTで膵頭部癌と診断された。腹部CTおよびMRIでは遠隔転移や大動脈周囲リンパ節(PALN)転移は認めなかった。手術の方針とし術中にPALNサンプリングを行ったところ、迅速病理診断にてリンパ節4個中2個に転移を認めた。非切除とした場合、腎機能障害のため標準的な化学療法を施行できないと考え、PALN郭清を伴う亜全胃温存膵頭十二指腸切除術を施行した。病理診断は浸潤性膵管癌であり、S-1による術後補助化学療法を減量して行った。術後1年10ヵ月で腸間膜内リンパ節再発および肺転移再発を認めた。さらに、術後2年で腹腔内再発による上腸間膜動静脈狭窄を認めた。腹腔内再発に対し放射線療法を行い、引き続きgemcitabine単独療法を行った。肝外門脈狭窄による腹水貯留や消化管出血は治療により軽快した。結果、術後5年7ヵ月の長期生存を得た。(著者抄録)

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The patient was a 64-year-old man with diagnosis of pancreatic head cancer. Initially, abdominal CT showed pancreatic head tumor with bile duct invasion and no distant metastases including para-aortic lymph nodes(PALN). Although, subtotal stomach-preserving pancreatoduodenectomy(SSPPD)and PALN sampling was performed, intraoperative frozen section examination revealed PALN metastasis. He had chronic kidney disease and was unsuitable for standard chemotherapy, SSPPD and PALN dissection was performed instead of standard chemotherapy. Histopathological examination of the resected specimens revealed invasive ductal carcinoma in the pancreatic head region and 11 nodes out of the 17 dissected PALN. Adjuvant chemotherapy with S-1 was performed. 22 months after surgery, intraabdominal lymph nodes metastasis and lung metastasis was found. 24 months after surgery, palliative radiation therapy at a dose of 40 Gy was performed. Systemic chemotherapy with gemcitabine alone was performed, but he was dead 67 months after the initial therapy.

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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BACKGROUND: Mesenteric lymph node (MLN) involvement is often observed in ovarian cancer (OC) with rectosigmoid invasion. This study aimed to investigate the clinical significance of MLN involvement in the pattern of liver metastasis in patients with OC. METHODS: We included 85 stage II-IV OC patients who underwent primary or interval debulking surgery. Twenty-seven patients underwent rectosigmoid resection, whose status of MLN involvement was judged from hematoxylin and eosin (H&E) staining of resected specimens. The prognostic significance of clinicopathological characteristics, including MLN involvement, was evaluated using univariate and multivariate analyses. RESULTS: MLN involvement was detected in 14/85 patients with stage II-IV OC. Residual tumor status, cytology of ascites, and MLN involvement were independent prognostic factors for progression-free survival (PFS; p = 0.033, p = 0.014, and p = 0.008, respectively). When patients were classified into three groups (no MLN, one MLN, two or more MLNs), the number of MLNs involved corresponded to three distinct groups in PFS (p = 0.001). The 3-year cumulative incidence of liver metastasis of patients with MLN involvement was significantly higher than that of patients without MLN involvement (61.1% vs. 8.9%, p < 0.001). MLN involvement was significantly associated with liver metastasis of hematogenous origin (p < 0.001) compared with peritoneal disseminated origin. CONCLUSION: MLN involvement is an important prognostic factor in OC, predicting poor prognosis and liver metastasis of hematogenous origin.

DOI： 10.1245/s10434-021-09899-8

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BACKGROUND: Chronic intestinal pseudo-obstruction (CIPO) is a severe and refractory intestinal motility disorder. However, due to its rarity and difficult histological investigation, its pathophysiology has not been characterized. AIM: Therefore, in this study, we aimed to determine the role of esophageal high-resolution manometry (HRM) in CIPO and the histological and clinical characteristics of the disease. METHODS: Patients with CIPO were analyzed for clinical characteristics; histological findings; and clinical courses after therapeutic intervention. In addition, HRM was performed to determine the esophageal involvement. RESULTS: Eleven patients were diagnosed with CIPO, and five required the long period of parenteral nutrition showing impaired esophageal motility including achalasia and absent contractility diagnosed with HRM. The four of these five cases showed acute onset of the CIPO following the triggering events of pregnancy, appendicitis, and surgery. In contrast, other six patients with normal or Jackhammer esophagus on HRM had moderate severity of CIPO with gradual onset. The histological analyses revealed that the loss of the intestinal neural ganglion cells and layers by inflammation, destruction, and atrophy are related to the severity of the clinical course of the disease and esophageal HRM findings of achalasia and absent contractility. CONCLUSIONS: HRM may be useful to diagnose the severity of the clinical course and to determine the therapeutic options for CIPO.

DOI： 10.1007/s10620-020-06701-9

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BACKGROUND: Activin A receptor type 2A (ACVR2A) is one of the most frequently mutated genes in microsatellite instability-high (MSI-H) gastric cancer. However, the clinical relevance of the ACVR2A mutation in MSI-H gastric cancer patients remains unclear. The aims of this study were to explore the effect of ACVR2A mutation on the tumor behavior and to identify the clinicopathological characteristics of gastric cancer patients with ACVR2A mutations. METHODS: An in vitro study was performed to investigate the biological role of ACVR2A via CRISPR/Cas9-mediated ACVR2A knockout MKN74 human gastric cancer cells. One hundred twenty-four patients with gastric cancer were retrospectively analyzed, and relations between MSI status, ACVR2A mutations, and clinicopathological factors were evaluated. RESULTS: ACVR2A knockout cells showed less aggressive tumor biology than mock-transfected cells, displaying reduced proliferation, migration, and invasion (P < 0.05). MSI mutations were found in 10% (13/124) of gastric cancer patients, and ACVR2A mutations were found in 8.1% (10/124) of patients. All ACVR2A mutations were accompanied by MSI. The 5-year overall survival rates of ACVR2A wild-type patients and ACVR2A-mutated patients were 57% and 90%, respectively (P = 0.048). Multivariate analysis revealed that older age (P = 0.015), distant metastasis (P < 0.001), and ACVR2A wild-type status (P = 0.040) were independent prognostic factors for overall survival. CONCLUSIONS: Our study demonstrated that gastric cancer patients with ACVR2A mutation have a significantly better prognosis than those without. Dysfunction of ACVR2A in MKN74 human gastric cancer cells caused less aggressive tumor biology, indicating the importance of ACVR2A in the progression of MSI-H tumors.

DOI： 10.1007/s11605-020-04889-9

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PURPOSE: This study aimed to elucidate the impact of anatomic location of residual disease (RD) after initial cholecystectomy on survival following re-resection of incidental gallbladder cancer (IGBC). METHODS: Patients with pT2 or pT3 gallbladder cancer (36 with IGBC and 171 with non-IGBC) who underwent resection were analyzed. Patients with IGBC were classified as follows according to the anatomic location of RD after initial cholecystectomy: no RD (group 1); RD in the gallbladder bed, stump of the cystic duct, and/or regional lymph nodes (group 2); and RD in the extrahepatic bile duct and/or distant sites (group 3). RESULTS: Timing of resection (IGBC vs. non-IGBC) did not affect survival in either multivariate or propensity score matching analysis. RD was found in 16 (44.4%) of the 36 patients with IGBC; R0 resection following re-resection was achieved in 32 patients (88.9%). Overall survival (OS) following re-resection was worse in group 3 (n = 7; 5-year OS, 14.3%) than in group 2 (n = 9; 5-year OS, 55.6%) (p = 0.035) or in group 1 (n = 20; 5-year OS, 88.7%) (p < 0.001). There was no survival difference between groups 1 and 2 (p = 0.256). Anatomic location of RD was independently associated with OS (group 2, HR 2.425, p = 0.223; group 3, HR 9.627, p = 0.024). CONCLUSION: The anatomic location of RD independently predicts survival following re-resection, which is effective for locoregional disease control in IGBC, similar to resection for non-IGBC. Not all patients with RD have poor survival following re-resection for IGBC.

DOI： 10.1007/s00423-021-02165-1

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AIMS: Tumour deposits (TDs) are an important prognostic marker in colorectal cancer. However, the classification, and inclusion in staging, of TDs has changed significantly in each tumour-node-metastasis (TNM) edition since their initial description in TNM-5, and terminology remains controversial. Expert consensus is needed to guide the future direction of precision staging. METHODS AND RESULTS: A modified Delphi consensus process was used. Statements were formulated and sent to participants as an online survey. Participants were asked to rate their agreement with each statement on a five-point Likert scale and also to suggest additional statements for discussion. These responses were circulated together with anonymised comments, and statements were modified prior to carrying out a second online round. Consensus was set at 70%. Overall, 32 statements reached consensus. There were concerns that TDs were currently incorrectly placed in the TNM system and that their prognostic importance was being underestimated. There were concerns regarding interobserver variation and it was felt that a clearer, more reproducible definition of TDs was needed. CONCLUSIONS: Our main recommendations are that the number of TDs should be recorded even if lymph node metastases (LNMs) are also present and that nodules with evidence of origin [extramural venous invasion (EMVI), perineural invasion (PNI), lymphatic invasion (LI)] should still be categorised as TDs and not excluded, as TNM-8 specifies. Whether TDs should continue to be included in the N category at all is controversial, and did not achieve consensus; however, participants agreed that TDs are prognostically worse than LNMs and the N1c category is suboptimal, as it does not reflect this.

DOI： 10.1111/his.14344

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Background: Esophageal involvement length (EIL) is a promising indicator of metastasis or recurrence in mediastinal lymph nodes (MLNs) in adenocarcinoma of the esophagogastric junction (EGJ). This study aimed to elucidate the accuracy of the preoperative endoscopic evaluations of EIL and its clinical significance in this disease. Materials and methods: In total, 75 patients with Siewert type II (N = 53) or III (N = 22) adenocarcinoma of the EGJ, who underwent surgical resection without preoperative therapy between 1995 and 2016 were enrolled. We retrospectively examined the accuracy of the preoperative endoscopic evaluations of EIL (preoperative EIL), compared to the pathologically evaluated EIL. Finally, we investigated the association between preoperative EIL and metastasis or recurrence in MLNs. Results: The accuracy of the preoperative EIL within a 1-cm interval was only 53.3%. Among patients with discordance between the pre- and postoperative evaluations, 68.6 % had the underestimation in the preoperative EIL. pN1-3 (OR = 5.85, 95% CI: 1.03-33.17) and undifferentiated histologic type (OR = 2.52, 95% CI: 0.89-7.14) were potential risk factors for the discordance. Regarding metastasis or recurrence in MLNs, preoperative EIL of 2-3 cm (OR = 10.41, 95% CI: 1.35-80.11) and >3 cm (OR = 8.33, 95% CI: 1.09-63.96) were independent predictors. Conclusion: Although the accuracy of the endoscopic evaluations of EIL is insufficient with many underestimations, EIL should be assessed in preoperative staging because of significant predictive power for metastasis or recurrence in MLNs.

DOI： 10.1016/j.amsu.2021.102590

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Language：Japanese   Publisher：(株)癌と化学療法社  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(株)癌と化学療法社  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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BACKGROUND: Tumor mutational burden-high (TMB-H), which is detected with gene panel testing, is a promising biomarker for immune checkpoint inhibitors (ICIs) in colorectal cancer (CRC). However, in clinical practice, not every patient is tested for TMB-H using gene panel testing. We aimed to identify the histopathological characteristics of TMB-H CRC for efficient selection of patients who should undergo gene panel testing. Moreover, we attempted to develop a convolutional neural network (CNN)-based algorithm to predict TMB-H CRC directly from hematoxylin and eosin (H&E) slides. METHODS: We used two CRC cohorts tested for TMB-H, and whole-slide H&E digital images were obtained from the cohorts. The Japanese CRC (JP-CRC) cohort (N = 201) was evaluated to detect the histopathological characteristics of TMB-H using H&E slides. The JP-CRC cohort and The Cancer Genome Atlas (TCGA) CRC cohort (N = 77) were used to develop a CNN-based TMB-H prediction model from the H&E digital images. RESULTS: Tumor-infiltrating lymphocytes (TILs) were significantly associated with TMB-H CRC (P < 0.001). The area under the curve (AUC) for predicting TMB-H CRC was 0.910. We developed a CNN-based TMB-H prediction model. Validation tests were conducted 10 times using randomly selected slides, and the average AUC for predicting TMB-H slides was 0.934. CONCLUSIONS: TILs, a histopathological characteristic detected with H&E slides, are associated with TMB-H CRC. Our CNN-based model has the potential to predict TMB-H CRC directly from H&E slides, thereby reducing the burden on pathologists. These approaches will provide clinicians with important information about the applications of ICIs at low cost.

DOI： 10.1007/s00535-021-01789-w

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Language：Japanese   Publisher：(一社)日本大腸肛門病学会  

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PURPOSE: Outcomes following surgery for advanced gallbladder carcinoma remain unsatisfactory. This study aimed to determine the surgical outcome and effectiveness of adjuvant chemotherapy according to TNM stage in patients with gallbladder carcinoma. METHODS: A total of 200 patients undergoing surgery for gallbladder carcinoma were enrolled. Clinicopathological data were evaluated and surgical outcomes were compared between patients with and without adjuvant chemotherapy according to TNM stage. RESULTS: The 5-year overall survival (OS) after resection for patients with stage I (n = 27), IIA (n = 18), IIB (n = 28), IIIA (n = 25), IIIB (n = 43), IVA (n = 7), and IVB (n = 52) disease was 90.8%, 94.4%, 73.6%, 33.7%, 57.7%, 14.3%, and 11.8%, respectively (p < 0.001). R0 resection was performed in all patients with stage I or II disease, in 89.7% of those with stage III disease, and 69.5% of those with stage IV disease. For patients with stage III disease, adjuvant chemotherapy was associated with improved OS (5-year OS, 60.9% vs. 41.1%; p = 0.028) and was an independent prognostic factor (hazard ratio, 2.045; p = 0.039). For patients with stage IV disease, adjuvant chemotherapy appeared to affect OS (5-year OS, 25.1% vs. 5.3%; p = 0.041); R0 resection (hazard ratio, 1.882; p = 0.040) was the only independent prognostic factor. CONCLUSION: TNM stage clearly predicts survival after resection of gallbladder carcinoma. R0 resection with adjuvant chemotherapy is recommended for long-term survival in the multimodal management of patients with stage III or IV gallbladder carcinoma.

DOI： 10.1007/s00423-020-02068-7

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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DOI： 10.1111/1346-8138.15800

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

DOI： 10.1245/s10434-021-09919-7

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Other Link： http://link.springer.com/article/10.1245/s10434-021-09919-7/fulltext.html

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PURPOSE: Clinical calculators and nomograms have been endorsed by the American Joint Committee on Cancer (AJCC), as they provide the most individualized and accurate estimate of patient outcome. Using molecular and clinicopathologic variables, a third-generation clinical calculator was built to predict recurrence following resection of stage I-III colon cancer. METHODS: Prospectively collected data from 1,095 patients who underwent colectomy between 2007 and 2014 at Memorial Sloan Kettering Cancer Center were used to develop a clinical calculator. Discrimination was measured with concordance index, and variability in individual predictions was assessed with calibration curves. The clinical calculator was externally validated with a patient cohort from Washington University's Siteman Cancer Center in St Louis. RESULTS: The clinical calculator incorporated six variables: microsatellite genomic phenotype; AJCC T category; number of tumor-involved lymph nodes; presence of high-risk pathologic features such as venous, lymphatic, or perineural invasion; presence of tumor-infiltrating lymphocytes; and use of adjuvant chemotherapy. The concordance index was 0.792 (95% CI, 0.749 to 0.837) for the clinical calculator, compared with 0.708 (95% CI, 0.671 to 0.745) and 0.757 (0.715 to 0.799) for the staging schemes of the AJCC manual's 5th and 8th editions, respectively. External validation confirmed robust performance, with a concordance index of 0.738 (95% CI, 0.703 to 0.811) and calibration plots of predicted probability and observed events approaching a 45° diagonal. CONCLUSION: This third-generation clinical calculator for predicting cancer recurrence following curative colectomy successfully incorporates microsatellite genomic phenotype and the presence of tumor-infiltrating lymphocytes, resulting in improved discrimination and predictive accuracy. This exemplifies an evolution of a clinical calculator to maintain relevance by incorporating emerging variables as they become validated and accepted in the oncologic community.

DOI： 10.1200/JCO.20.02553

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Language：Japanese   Publisher：(一社)日本内視鏡外科学会  

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It is reported that an increase in aerobic bacteria, a lack of short-chain fatty acids (SCFAs), and immune disorders in the diverted colon are major causes of diversion colitis. However, the precise pathogenesis of this condition remains unclear. The aim of the present study was to examine the microbiota, intestinal SCFAs, and immunoglobulin A (IgA) in the diverted colon. Eight patients underwent operative procedures for colostomies. We assessed the diverted colon using endoscopy and obtained intestinal samples from the diverted colon and oral colon in these patients. We analyzed the microbiota and SCFAs of the intestinal samples. The bacterial communities were investigated using a 16S rRNA gene sequencing method. The microbiota demonstrated a change in the proportion of some species, especially Lactobacillus, which significantly decreased in the diverted colon at the genus level. We also showed that intestinal SCFA values were significantly decreased in the diverted colon. Furthermore, intestinal IgA levels were significantly increased in the diverted colon. This study was the first to show that intestinal SCFAs were significantly decreased and intestinal IgA was significantly increased in the diverted colon. Our data suggest that SCFAs affect the microbiota and may play an immunological role in diversion colitis.

DOI： 10.1016/j.bbrep.2020.100892

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Language：Japanese   Publisher：(一社)日本内視鏡外科学会  

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Language：Japanese   Publisher：(一社)日本胃癌学会  

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BACKGROUND/AIM: This study aimed to evaluate how NAD(P)H: quinone oxidoreductase-1 (NQO1) affects survival after hepatectomy in patients with colorectal liver metastasis (CRLM). PATIENTS AND METHODS: A retrospective analysis was conducted of 88 consecutive patients who underwent hepatectomy for CRLM. Of the 88 patients, preoperative chemotherapy was administered to 30 patients. Immunohistochemistry of the resected specimens was conducted using monoclonal anti-NQO1 antibody. RESULTS: NQO1-positive expression in tumor cells of CRLM was associated with worse overall survival (p=0.026) and was an independent adverse prognostic factor in multivariate analysis (hazard ratio=5.296, p=0.007). Among 30 patients who received preoperative chemotherapy, patients with loss of NQO1 expression in non-neoplastic epithelial cells of the bile ducts (NQO1 polymorphism: n=19) showed significantly better response to preoperative chemotherapy for CRLM (p=0.004). CONCLUSION: NQO1-positive expression in tumor cells of CRLM may be an adverse prognostic factor after hepatectomy for CRLM.

DOI： 10.21873/anticanres.14916

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AIM: The role of preoperative frailty assessment in patients with gastrointestinal (GI) disease remains unclear. This study aimed to clarify the relationship between frailty and postoperative outcomes in patients with GI disease. METHODS: This study investigated 42 patients (aged ≥65 years) with GI disease who underwent abdominal surgery. The frailty status was analyzed using the Japanese version of the Cardiovascular Health Study criteria. We also investigated postoperative outcomes. RESULTS: Of the 42 patients, seven (16.7%) were robust, 24 (57.1%) were prefrail and 11 (26.2%) were frail. Postoperative complications were observed in 45.5% and 63.6% of prefrail and frail patients, respectively, whereas no complications were found in robust patients (P = 0.026). The median hospital stay was 15, 19.5 and 27 days in robust, prefrail and frail patients, respectively (P < 0.01). CONCLUSION: Preoperative frailty status based on the Japanese version of the Cardiovascular Health Study criteria is associated with postoperative complication incidence and hospital stay extension in patients with GI disease. Geriatr Gerontol Int 2021; ••: ••-••.

DOI： 10.1111/ggi.14134

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Language：Japanese   Publisher：(株)へるす出版  

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Language：Japanese   Publisher：(一社)日本大腸肛門病学会  

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BACKGROUND: This study aimed to investigate the impact of surgery on outcomes in patients with recurrent biliary tract cancer (BTC) and elucidate factors affecting survival after surgery for this disease. METHODS: A single-center study was undertaken in 178 patients with recurrent BTC, of whom 24 underwent surgery for recurrence, 85 received chemotherapy, and 69 received best supportive care. Then, we carried out a multicenter study in 52 patients undergoing surgery for recurrent BTC (gallbladder cancer, 39%; distal cholangiocarcinoma, 27%; perihilar cholangiocarcinoma, 21%; intrahepatic cholangiocarcinoma, 13%). RESULTS: In the single-center study, 3-year survival after recurrence was 53% in patients who underwent surgery, 4% in those who received chemotherapy, and 0% in those who received best supportive care (p < 0.001). Surgery was an independently prognostic factor (p < 0.001). In the multicenter series, the respective 3-year and 5-year survival after surgery for recurrence was 50% and 29% in the 52 patients. Initial site of recurrence was the only independent prognostic factor (p = 0.019). Five-year survival after surgery for recurrence in patients with single distant, multifocal distant, and locoregional recurrence was 51%, 0%, and 0%, respectively (p = 0.002). Sites of single distant recurrence included the liver (n = 13, 54%), distant lymph nodes (all from gallbladder cancer, n = 7, 29%), lung (n = 2, 9%), peritoneum (n = 1, 4%), and abdominal wall (n = 1, 4%). CONCLUSION: Surgery may be an effective option for patients with less aggressive tumor biology characterized by single distant recurrence in recurrent BTC.

DOI： 10.1016/j.hpb.2021.01.007

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Language：Japanese   Publisher：(株)篠原出版新社  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

Some bacteria are symbiotic in tumor tissues, and metabolites of several bacterial species have been found to cause DNA damage. However, to date, the association between bacteria and host genetic alterations in colorectal cancer (CRC) has not been fully investigated. We evaluated the association between the intra-tumor microbiome and host genetic alterations in 29 Japanese CRC patients. The tumor and non-tumor tissues were extracted from the patients, and 16S rRNA genes were sequenced for each sample. We identified enriched bacteria in tumor and non-tumor tissues. Some bacteria, such as Fusobacterium, which is already known to be enriched in CRC, were found to be enriched in tumor tissues. Interestingly, Bacteroides, which is also known to be enriched in CRC, was enriched in non-tumor tissues. Furthermore, it was shown that certain bacteria that often coexist within tumor tissue were enriched in the presence of a mutated gene or signal pathway with mutated genes in the host cells. Fusobacterium was associated with many mutated genes, as well as cell cycle-related pathways including mutated genes. In addition, the patients with a high abundance of Campylobacter were suggested to be associated with mutational signature 3 indicating failure of double-strand DNA break repairs. These results suggest that CRC development may be partly caused by DNA damage caused by substances released by bacterial infection. Taken together, the identification of distinct gut microbiome patterns and their host specific genetic alterations might facilitate targeted interventions, such as modulation of the microbiome in addition to anticancer agents or immunotherapy.

DOI： 10.1016/j.csbj.2021.05.049

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(株)癌と化学療法社  

症例は72歳、男性。下血を主訴に来院し、大腸内視鏡検査で肛門縁から5cmの直腸前壁に下縁を有する2型腫瘍を指摘された。生検で高分化管状腺癌であった。術前胸腹骨盤部CT検査の結果遠隔転移は認めず、下部直腸癌、cT3N0M0、cStage IIaと診断された。術前の全身検査で徐脈性心房細動および重症肺気腫を認め、全身麻酔のリスクが高い症例と判断された。ペースメーカー留置後、術前化学放射線療法(CRT)(capecitabine併用、1.8Gy28回、計50.4Gy)を開始した。術前CRT後4週間目の直腸診および画像評価では腫瘍は消失し、生検で悪性所見を認めなかった。十分なインフォームド・コンセントの下、全身麻酔のリスクを勘案し、"watch and wait治療"の方針とした。現在、術前CRT後15ヵ月経過し局所の再増大および遠隔転移を認めず、経過観察を行っている。(著者抄録)

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J00296&link_issn=&doc_id=20210118600073&doc_link_id=%2Fab8gtkrc%2F2020%2F004713%2F073%2F1960b1962%26dl%3D3&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fab8gtkrc%2F2020%2F004713%2F073%2F1960b1962%26dl%3D3&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_4.gif

Language：Japanese   Publisher：(株)癌と化学療法社  

症例は63歳、女性。黄疸を契機に発見された膵頭部癌で、CTで上腸間膜動脈起始部の大動脈前面にリンパ節転移を認めた。nab-PTX+GEM併用療法を開始し、5コース後の治療効果判定は部分奏効PRで、初診から6ヵ月後に亜全胃温存膵頭十二指腸切除術を施行した。病理組織学的診断は浸潤性膵管癌で、ypT2N1bM0、Stage IIBであった。術後補助化学療法としてS-1療法を行った。術後14ヵ月で腹壁瘢痕ヘルニア近傍の臍部に臍転移(Sister Mary Joseph's nodule:SMJN)を認めた。他の遠隔転移は認めず、腫瘤切除および腹壁瘢痕ヘルニア修復術を施行した。病理組織学的診断では膵癌の転移であった。引き続きGEMOX療法を行ったが、臍切除3ヵ月後に多発の皮膚転移が出現した。mFOLFIRINOX療法に変更したが皮膚転移は増悪し、出血と疼痛の症状緩和のため皮膚切除した。化学療法を継続したが徐々に全身状態が悪化し、初診から2年5ヵ月(臍切除後7ヵ月)で死亡した。(著者抄録)

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Language：Japanese   Publisher：(株)癌と化学療法社  

症例は64歳、男性。肝機能障害の精査で肝門部領域胆管癌と診断された。腫瘍は右側優位のBismuth分類IV型で、門脈右枝〜左右分枝への浸潤が認められた。肝予備能、残肝容積は十分であり、拡大肝右葉切除術+肝外胆管切除術+門脈合併切除術が実施された。術中迅速組織診断で十二指腸側・肝側胆管切離断端がともに浸潤癌陽性となったが、進行度や侵襲度を勘案し、膵頭十二指腸切除術の追加や左肝管断端の追加切除は行わなかった。最終的な進行度はpT4b、pN0、cM0、Stage IV A、pDMI(w)、pHM1(w)、pPV1(a)、R1であった。術後化学療法としてgemcitabine(GEM)+cisplatin療法を1年、GEM療法を1年実施した後、S-1療法を継続している。術後5年3ヵ月経過した現在、無再発生存中である。(著者抄録)

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Language：Japanese   Publisher：(株)癌と化学療法社  

症例は73歳、男性。貧血精査目的の上部消化管内視鏡検査で、食道胃接合部に白色から発赤調で易出血性の不整な隆起性腫瘤を認めた。生検では充実型低分化腺癌が疑われたが確定診断が得られず、追加で施行した免疫組織化学染色で悪性黒色腫と診断した。食道胃接合部原発の悪性黒色腫、cT3N1M1(副腎、骨)、cStage IVb(食道癌取扱い規約第15版)に対して、ペムブロリズマブの投与を行ったが肺転移が出現し原病死した。本例は腫瘍の主局在が胃側にあり、メラニン欠乏性悪性黒色腫であったため典型的な肉眼的・組織学的所見が得られず診断に難渋した。食道胃接合部の腫瘍においても、メラニン欠乏性悪性黒色腫の可能性を念頭に置いて診断を行う必要がある。(著者抄録)

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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The patient was a 63-year-old woman with diagnosis of pancreatic cancer. Abdominal CT showed pancreatic head tumor and paraaortic lymph node metastasis. We performed chemotherapy with nab-paclitaxel plus gemcitabine. After 5 courses of chemotherapy, the tumor reduced in size. Pancreaticoduodenectomy followed by adjuvant chemotherapy with S-1 was performed. Fourteen months after surgery, umbilical metastasis(Sister Mary Joseph's nodule: SMJN)was found in the umbilicus near the abdominal incisional hernia. There was no evidence of metastasis except in the umbilicus, we performed the umbilical tumor resection and abdominal incisional hernia repair. Pathological diagnosis was pancreatic cancer metastasis. Although following chemotherapy, multiple skin metastases was found in the lower abdomen 3 months after umbilical resection. We performed skin metastases resection to relieve pain and symptoms of bleeding. But she died 29 months after the initial therapy(7 months after umbilical resection).

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A 73-year-old man presented with anemia, and gastroscopy showed a nonpigmented tumor in the esophagogastric junction. The result of the tumor biopsy initially suspected poorly differentiated adenocarcinoma. However, additional immunohistochemical examination revealed malignant melanoma. The final diagnosis was amelanotic malignant melanoma of the esophagogastric junction with adrenal and spinal metastasis. Although immunotherapy was performed, the patient died 132 days after diagnosis.

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A 64-year-old man with liver dysfunction was given a diagnosis of perihilar cholangiocarcinoma(Bismuth type Ⅳ). The tumor was predominantly right-sided and invaded to the bifurcation of the right and left portal veins. After confirming sufficient liver functional reserve and future liver remnant, the patient underwent extended right hepatectomy, extrahepatic bile duct resection, and portal vein resection and reconstruction. Intraoperative examination of frozen sections revealed the presence of residual invasive carcinoma on both the hepatic and duodenal sides of the ductal resection margins. However, we did not perform pancreaticoduodenectomy or additional resection of the margin-positive proximal bile duct considering the curability and invasiveness of these procedures. He received postoperative chemotherapy with biweekly gemcitabine plus cisplatin for 1 year, followed by gemcitabine monotherapy for 1 year, and S-1 monotherapy has been performed since then. He remains alive and well with no evidence of disease 63 months after surgery.

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BACKGROUND: Solitary fibrous tumor (SFT), a mesenchymal fibroblastic tumor with a hypervascular nature, rarely develops in the pelvis. Resection of a giant SFT occupying the pelvic cavity poses an increased risk of developing massive hemorrhage during resection, although surgical resection is the most effective treatment method for this tumor to achieve a potential cure. SFT rarely develops with Doege-Potter syndrome, which is known as a paraneoplastic syndrome characterized by non-islet cell tumor hypoglycemia (NICTH) secondary to SFT that secretes insulin-like growth factor-II (IGF-II). We present a case of a giant pelvic SFT with Doege-Potter syndrome, which was successfully treated with transcatheter arterial embolization (TAE) followed by surgical resection. CASE PRESENTATION: A 46-year-old woman presented with a disorder of consciousness due to refractory hypoglycemia. Images of the pelvis showed a giant and heterogeneously hypervascular mass displacing and compressing the rectum. Endocrinological evaluation revealed low serum levels of insulin and C-peptide consistent with NICTH. Angiography identified both the inferior mesenteric artery and the bilateral internal iliac artery as the main feeders of the tumor. To avoid intraoperative massive bleeding, super-selective TAE was performed for the tumor 2 days prior to surgery. Hypoglycemia disappeared after TAE. The tumor was resected completely, with no massive hemorrhage during resection. Histologically, it was diagnosed as IGF-II-secreting SFT. Partial necrosis of the rectum in the specimen was observed due to TAE. The patient was followed up for 2 years and no evidence of disease has been reported. CONCLUSIONS: Preoperative angiography followed by TAE is an exceedingly helpful method to reduce intraoperative hemorrhage when planning to resect SFT occupying the pelvic cavity. Complications related to ischemia should be kept in mind after TAE, which needs to be planned within 1 or 2 days before surgery. TAE for tumors may be an option in addition to medical and surgical treatment for persistent hypoglycemia in Doege-Potter syndrome.

DOI： 10.1186/s40792-020-01076-5

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Tumor infiltrating lymphocytes (TIL), which represent host adaptive response to the tumor, were first identified at scanning magnification to select areas with the highest counts on hematoxylin and eosin slides, quantitated per high-power field (HPF), and analyzed for association with recurrence-free survival (RFS) in 848 patients. Highest TIL in a single HPF was analyzed as a continuous and categorical variable, and optimal cutoff analysis was performed to predict RFS. Highest TIL count in a single HPF ranged from 0 to 45, and the optimal cutoff for TIL high vs TIL low was determined to be ≥ 3 vs < 3 with a concordance probability estimate of 0.74. In the entire cohort, 5-year RFS was 90.2% (95% CI = 83.7-94.2) in TIL high compared to 78.9% (95% CI = 74.1-82.9) in TIL low (log rank P < .0001). TIL remained significant in the mismatch repair-proficient (pMMR) cohort where 5-year RFS was 94.6% (95% CI = 88.3-97.5) in TIL high compared to 77.9% (95% CI = 69.2-84.4) in TIL low (P = .008). On multivariable analysis, TIL and AJCC Stage were independently associated with RFS in the pMMR cohort. Qualitatively in the pMMR cohort, RFS in Stage II TIL high patients was similar to that in Stage I patients and RFS in Stage III TIL high was similar to that in Stage II TIL low patients. Assessment of TIL in a single HPF using standard H&E slides provides important prognostic information independent of MMR status and AJCC stage.

DOI： 10.1080/2162402X.2020.1841948

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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PURPOSE: The 9th Japanese Classification of Colorectal Cancer (9th JSCCR) has two main differences from the TNM classification (8th AJCC): first, main or lateral lymph node metastasis is classified as jN3; second, tumor nodules (ND) are treated as lymph node metastasis. In this study, we verified the 9th JSCCR for rectal cancer, focusing on the differences with the 8th AJCC. METHODS: This retrospective analysis involved 212 patients with stage I-III rectal cancer. ND was evaluated using whole-mount sections. We evaluated the relapse-free survival of each staging system, and compared the prognostic significance of the different staging systems using the Akaike information criterion (AIC) and Harrell's concordance index (c-index). RESULTS: Main or lateral lymph node metastasis was detected in nine of 212 (4%) patients. ND was detected in 79 of 212 (37%) patients. The best risk stratification power was observed in the 9th JSCCR (AIC, 759; c-index, 0.708) compared with the 7th JSCCR (AIC, 771; c-index, 0.681), 8th JSCCR (AIC, 768; c-index, 0.696), and the 8th AJCC (AIC, 766; c-index, 0.691). CONCLUSIONS: The 9th JSCCR, which includes the concepts of jN3 and ND, is useful for the risk stratification of rectal cancer, and the contributes to precise decision-making for follow-up management and adjuvant therapy.

DOI： 10.1007/s00595-020-02024-4

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Language：Japanese   Publisher：日本消化器病学会-甲信越支部  

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Language：Japanese   Publisher：日本消化器病学会-甲信越支部  

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Language：Japanese   Publisher：日本消化器病学会-甲信越支部  

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Language：Japanese   Publisher：日本消化器病学会-甲信越支部  

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BACKGROUND: The 8th edition of the American Joint Committee on Cancer (AJCC) TNM staging system provided a specific 'ypTNM' stage grouping for patients with esophageal cancer. OBJECTIVE: This study aimed to evaluate the clinical utility of the AJCC 8th edition ypTNM stage grouping for patients with esophageal squamous cell carcinoma (ESCC). METHODS: We enrolled 152 patients with ESCC who underwent surgery after neoadjuvant cisplatin plus 5-fluorouracil (CF) therapy between June 2005 and December 2011. ypStage was evaluated according to the AJCC 7th and 8th editions. Predictive performance for disease-specific survival (DSS) and overall survival (OS) was compared between both editions. The prognostic significance of ypTNM stage grouping was evaluated using univariate and multivariate analyses. RESULTS: Revision of the AJCC 7th edition to the 8th edition was associated with a change in ypStage in 96 patients (63.2%). The AJCC 8th edition revealed a better predictive performance than the 7th edition in terms of DSS (Akaike's information criterion [AIC] 499 vs. 513; Bayesian information criterion [BIC] 505 versus 519; concordance index [C-index] 0.725 versus 0.679) and OS (AIC 662 vs. 674; BIC 669 vs. 681; C-index 0.662 vs. 0.622). On univariate and multivariate analyses, ypStage in the 8th edition was an independent prognostic factor for both DSS and OS. CONCLUSIONS: ypTNM stage grouping in the AJCC 8th edition provided a better predictive performance for DSS and OS than that in the 7th edition. ypStage in the 8th edition was the most reliable prognostic factor for ESCC patients who underwent surgery after neoadjuvant CF therapy.

DOI： 10.1245/s10434-020-09181-3

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DOI： 10.1245/s10434-020-09184-0

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Language：Japanese   Publisher：日本臨床外科学会  

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Language：Japanese   Publisher：日本臨床外科学会  

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Language：Japanese   Publisher：医学図書出版(株)  

胆嚢癌根治手術の際の至適リンパ節郭清範囲に関して、文献をレビューすることで考察した。本邦、AJCC、UICCのすべての規約において、肝十二指腸間膜内および総肝動脈幹リンパ節は領域リンパ節に含まれている。しかし、本邦の規約のみ上膵頭後部リンパ節が、UICCの規約のみ腹腔動脈周囲および上腸間膜動脈リンパ節が領域リンパ節に含まれていることが規約間の相違点である。転移頻度と切除成績の両者の観点から、上膵頭後部リンパ節は領域リンパ節として取り扱うのが妥当である。一方、腹腔動脈周囲および上腸間膜動脈リンパ節は、少数の転移陽性症例の検討が存在するにすぎず、現時点では、領域リンパ節とすることは推奨できない。進行胆嚢癌において、腫瘍学的に根治をめざして郭清するべきリンパ節の至適範囲は、本邦の胆道癌取扱い規約第6版の定める領域リンパ節とすることが妥当である。(著者抄録)

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Language：Japanese   Publisher：(一社)日本大腸肛門病学会  

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BACKGROUND: To assess the potential of the ultrasonographic sliding lung sign to detect severe intrathoracic adhesions before surgery. METHODS: This was a prospective, single-center, observational study including all patients aged 20-89 years undergoing elective thoracic surgery. Patients with pneumothorax, pyothorax, hemothorax, chylothorax, and hydrothorax were excluded. We recorded the ultrasound sliding lung sign, surgical characteristics, and follow-up parameters: past medical history, respiratory function, chest X-ray findings, and computed tomography (CT) findings. Severe intrathoracic adhesion was defined as the need for adhesiolysis requiring more than 30 minutes. RESULTS: A total of 168 patients consented to participate. All 15 patients without the sliding lung sign had hard severe adhesions [specificity 100%, sensitivity 88.2%, positive predictive value (PPV) 100%, negative predictive value (NPV) 98.7%, and area under curve (AUC) 0.94]. There were two false-negative results, both of which were soft adhesions. Although blunting of the costophrenic (CP) angle, CT findings, past medical history, and restrictive lung disease were identified as significant risk factors of severe intrathoracic adhesion, all areas under the curve were low (0.71, 0.71, 0.69, 0.61, respectively). Thoracotomy frequency, intraoperative bleeding, operative time, and postoperative hospitalization were significantly greater in these patients than in those with non-severe adhesions. CONCLUSIONS: The ultrasound sliding lung sign could be used to predict severe intrathoracic adhesions before surgery. Preoperative confirmation of the ultrasound sliding lung sign is important for planning surgical approaches and implementing appropriate safety management.

DOI： 10.21037/jtd-20-886

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(株)癌と化学療法社  

症例は30歳代、女性。家族歴は父、父方祖父、母方祖母が大腸癌である。高頻度マイクロサテライト不安定性(high-frequency microsatellite instability:MSI-H)Stage II大腸癌の術後経過観察中に、腹膜播種再発および多発大腸癌を指摘された。現病歴および家族歴からリンチ症候群が疑われたため、当院を紹介された。当院では腹膜播種再発と、その後の腹膜播種再々発に対して2回のR0切除術を施行した。腹膜播種再発の癌組織を用いて、次世代シークエンサーを用いた遺伝子パネル検査を施行したところ、MSH2変異(c.A2211-2G)を認めた。本症例では、生殖細胞系列におけるMSH2変異がリンチ症候群の原因遺伝子変異となり、MSI-H大腸癌の発生に関与している可能性がある。今後は、必要に応じて遺伝カウンセリングや生殖細胞系列の遺伝子変異検査を実施する予定である。(著者抄録)

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Here, we report about a woman in her 30s who had peritoneal dissemination and multiple colon cancer with high-frequency microsatellite instability(MSI-H). Her father, paternal grandfather, and maternal grandmother had a history of colorectal cancer treatment. Thus, Lynch syndrome was suspected. We performed R0 resection for peritoneal dissemination and subsequent peritoneal dissemination. A 435-gene panel testing using a next-generation sequencer identified MSH2 and other mutations in the tumor. Hence, we speculated that she could have a germline mutation of MSH2, which causes Lynch syndrome. In the future, if she wishes to receive genetic counseling and undergo germline testing for variants to confirm the diagnosis of Lynch syndrome, we will perform them after receiving informed consent.

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Biliary tract cancer (BTC) is clinically and pathologically heterogeneous and responds inadequately to treatment. A small section of patients develop resectable disease, although the relapse rates are high; the benefits of adjuvant capecitabine chemotherapy for BTC are now understood, and gemcitabine-based combination chemotherapy is the first line of therapeutic strategy for BTC; however, alternative therapy for BTC is not known. Genomic profiling can provide detailed information regarding the carcinogenesis, identification, and therapy for BTC. Currently, confirmed restorative targets for BTC are lacking. In this review, we aimed to analyze the preclinical and clinical implications of a spectrum of genomic alterations associated with new potentially remedial targets. We focused on eight draggable genes for BTC, which were described as having evidence of therapeutic impact (evidence level 2A-3B) based on the clinical practice guidance for next-generation sequencing in cancer diagnosis and treatment; these include ERBB2, NTRK1, RNF43, CDK6, CDKN2B, FGFR2, IDH1, and IDH2. Moreover, some of the BTC present microsatellite instability, hypermutation, and germline variants, which we also reviewed. Finally, we discussed the therapeutic options based on the next-generation sequencing findings in BTC. Studies have demonstrated that BTC includes subgroups with individually distinct driver mutations, most of which will be targeted with new treatment plans.

DOI： 10.1002/ags3.12334

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Language：Japanese   Publisher：(一社)日本大腸肛門病学会  

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Nearly 50% of primary lung carcinoma patients present with distant metastasis at their first visit. However, gastrointestinal tract (GIT) metastasis is an infrequent impediment. Herein, we report a case of progressive dysphagia and epigastralgia as an initial manifestation of recurrence as gastric metastasis of primary lung squamous cell carcinoma (SCC) after curative surgery. A 64-year-old man was diagnosed with primary lung SCC of the right lower lobe, and underwent thoracoscopic lower lobectomy. One year after lobectomy, computed tomography (CT) scan showed a gastric fundal mass located in the gastric cardia which measured 5 cm. Endoscopic biopsies and histopathology subsequently confirmed that tumor was SCC. The patient then underwent proximal gastrectomy with resection of the diaphragmatic crus. Following surgery, histopathological examination revealed gastric metastasis from primary lung SCC. KEY POINTS: Gastric metastasis of primary lung carcinoma is one of the rarest phenomena. Gastrointestinal symptoms should raise suspicion of the presence of advanced metastatic disease with poor prognosis.

DOI： 10.1111/1759-7714.13410

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Right-sided colorectal cancer (RCRC) demonstrates worse survival outcome compared with left-sided CRC (LCRC). Recently, the importance of RNF43 mutation and BRAF V600E mutation has been reported in the serrated neoplasia pathway, which is one of the precancerous lesions in RCRC. It was hypothesized that the clinical significance of RNF43 mutation differs according to primary tumor sidedness. To test this hypothesis, the clinicopathological characteristics and survival outcome of patients with RNF43 mutation in RCRC and LCRC were investigated. Stage I-IV CRC patients (n=201) were analyzed. Genetic alterations including RNF43 using a 415-gene panel were investigated. Clinicopathological characteristics between RNF43 wild-type and RNF43 mutant-type were analyzed. Moreover, RNF43 mutant-type was classified according to primary tumor sidedness, i.e., right-sided RNF43 mutant-type or left-sided RNF43 mutant-type, and the clinicopathological characteristics between the two groups were compared. RNF43 mutational prevalence, spectrum and frequency between our cohort and TCGA samples were compared. RNF43 mutation was observed in 27 out of 201 patients (13%). Multivariate analysis revealed that age (≥65), absence of venous invasion, and BRAF V600E mutation were independently associated with RNF43 mutation. Among the 27 patients with RNF43 mutation, 12 patients were right-sided RNF43 mutant-type and 15 left-sided RNF43 mutant-type. Right-sided RNF43 mutant-type was significantly associated with histopathological grade 3, presence of lymphatic invasion, APC wild, BRAF V600E mutation, microsatellite instability-high (MSI-H), and RNF43 nonsense/frameshift mutation compared with left-sided RNF43 mutant-type. Similarly, RNF43 nonsense/frameshift mutations were more frequently observed in RCRC compared with LCRC in the TCGA cohort (P=0.042). Right-sided RNF43 mutant-type exhibited significantly worse overall survival than RNF43 wild-type and left-sided RNF43 mutant-type (P=0.001 and P=0.023, respectively) in stage IV disease. RNF43 mutation may be a distinct molecular subtype which is associated with aggressive tumor biology along with BRAF V600E mutation in RCRC.

DOI： 10.3892/or.2020.7561

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Language：English   Publisher：(一社)日本胃癌学会  

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BACKGROUND: Several tape fixations for chest tube were proposed, although none have a clear scientific basis. We performed a multicenter survey study to investigate the fixation of chest tubes using an available adhesive tape. We evaluated the strength of tape fixation and the effect of the skin coating material used on the fixation strength. METHODS: A multi-center questionnaire survey was administered in hospitals with a thoracic surgery division. The net promoter score (NPS) was used to measure the medical staff's satisfaction with an adhesive tape fixation. Fixing strength was calculated as follows: a chest tube was fixed using each taping method to a polyethylene plate and was pulled out in the long axis direction. While pulling out, the maximum resistance force [Newton (N)] and total resistance force [Joule (J)] were measured to calculate the fixing strength. RESULTS: The doctors' NPS showed no significant difference between handmade tape fixation and Quickfix {7 [5-8] vs. 10 [5-10] points, P=0.34}. The nurses' NPS showed no significant difference between handmade tape fixation and Quickfix {5 [5-8] vs. 5 [5-7] points, P=0.72}. The average maximum resistance force was the highest for Quickfix (1.36 J, 65.4 N) and a type of handmade fixation (three sheets stuck with foundation tape plus Y-shape slit plus Ω-shape tape; 1.61 J and 54.0 N). The fixation strength of Quickfix did not decrease with a skin coating agent (from 1.24 to 1.11 J and 63.0 to 66.6 N), although that of a handmade tape fixation decreased (from 1.49 to 0.90 J, 52.6 to 38.1 N). CONCLUSIONS: Quickfix provided secure fixation, regardless of the tube size or skin coating. Quickfix may be the best for standardized fixation because it is not only a stronger agent but is safe, simple, inexpensive, reliable, and can be used successfully by anyone.

DOI： 10.21037/jtd.2019.12.132

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Language：Japanese   Publisher：(一社)日本大腸肛門病学会  

症例は68歳,男性.慢性腎不全による高カリウム血症に対しポリスチレンスルホン酸ナトリウムを内服中に急性心不全を発症し,弁置換術,弁形成術が施行された.術後9日目に腹痛と血便が出現した.上行結腸壊死による汎発性腹膜炎と診断し,結腸右半切除と二連銃式の人工肛門造設術を行った.術後半年後の人工肛門閉鎖の際に左側結腸に狭窄を認め,残存結腸全摘,直腸S状部切除を行った.下行結腸に著明な狭窄を伴う縦走潰瘍瘢痕を,S状結腸に潰瘍形成を認めた.病理組織検査では狭窄部,潰瘍部の腸管壁内に好塩基性結晶様異物を認め,異物反応を伴っていた.ポリスチレンスルホン酸塩が腸管壁内に取り込まれると排除困難で,慢性的な異物反応や炎症により組織障害が遷延する可能性がある.慢性腎不全患者の腸管壊死,穿孔,腸炎に対し手術を行う際には,ポリスチレンスルホン酸塩製剤の内服歴を確認し,腸切除範囲の決定や吻合の可否に注意する必要がある.(著者抄録)

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Language：English   Publishing type：Research paper (scientific journal)  

Introduction: There are no specific standards for the timing of surgery to treat ulcerative colitis, so reaching a decision on timing is often difficult. Objective: The aim of this study was to evaluate the timing of surgery from the patients' perspective. Methods: From among 203 patients who underwent restorative proctocolectomy with ileal pouch anal anastomosis to treat ulcerative colitis at our hospital from 1985 to 2013, we mailed a questionnaire to 101 of those who are currently attending periodic follow-up at our hospital. Results: We analyzed 72 valid responses (71.2%). Overall, 65 patients (90.3%) responded that they were happy that they underwent surgery, 38 patients (52.8%) responded that the timing of surgery was appropriate, and 32 patients (44.4%) responded that they would have preferred to have had surgery earlier. The group of patients who would have preferred to have had surgery earlier included 23 patients (71.9%) who had undergone emergency surgery; the incidence of emergency surgery was significantly higher than in the group of 13 patients (34.2%) who had responded that the timing of surgery was appropriate (p = 0.002). Scores on the Medical Outcomes Study 36-Item Short-Form Health Survey (SF36), which reflect postoperative quality of life, were maintained at the same level as the Japanese standard values in our Japanese patients. Conclusion: The degree of satisfaction of patients who underwent surgery for ulcerative colitis was favorable, although it is important to consider surgery at an earlier stage in patients who may need emergency surgery.

DOI： 10.1159/000504885

PubMed

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Gastric cancer is one of the most common and clinically important diseases worldwide. The traditional Laeuren classification divides gastric cancer into two histopathological subtypes: diffuse and intestinal. Recent cancer genomics research has led to the development of a new classification based on molecular characteristics. The newly defined genomically stable (GS) subtype shares many cases with the histopathologically diffuse type. In this study, we performed genetic profiling of recurrently and significantly mutated genes in diffuse type and GS subtype tumors. We observed significantly different genetic characteristics, although the two subtypes overlapped in many cases. In addition, based on the profiles of the significantly mutated genes, we identified molecular functions and mutational signatures characteristic of each subtype. These results will advance the clinical application of the diffuse type and GS subtype gastric cancer in precision medicine for treating gastric cancer.

DOI： 10.1016/j.csbj.2020.10.021

PubMed

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Language：Japanese   Publishing type：Research paper (scientific journal)  

A 78-year-old woman was endoscopically followed up for benign melanocytosis in the middle thoracic esophagus that was detected 3 years prior. She presented with chest tightness, and an endoscopic examination revealed a protruding tumor at the melanotic lesion. She was histologically diagnosedwith an esophageal primary malignant melanoma. Computedtomography showedno metastatic lesions. She underwent minimally invasive esophagectomy with 2-fieldlymphad enectomy. Immunotherapy with nivolumab is ongoing for liver metastasis, which developed1 year and6 months after esophagectomy. Careful follow-up for esophageal melanocytosis is important for early diagnosis of esophageal primary malignant melanoma.

PubMed

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Language：Japanese   Publishing type：Research paper (scientific journal)  

A 66-year-old man with middle thoracic esophageal squamous cell carcinoma with supraclavicular lymph node metastasis visited our hospital. He underwent 3 courses of preoperative chemotherapy with docetaxel, cisplatin, and 5-FU(DCF)with a clinically-determined partial response. Minimally-invasive esophagectomy with 3-fieldlymphad enectomy was subsequently performed. Histopathologic examination revealedno viable tumor cells in the resectedesophagus andsupraclavicular lymph node. DCF is a promising preoperative chemotherapy regimen for locally advanced esophageal cancer because of its higher complete response rate comparedto that for cisplatin plus 5-FU.

PubMed

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Language：Japanese   Publisher：(株)癌と化学療法社  

症例は78歳、女性。健診目的の上部消化管内視鏡検査で胸部中部食道に食道メラノーシスを認め、経過観察されていた。3年後に胸部圧迫感を自覚し上部消化管内視鏡検査を施行したところ、食道メラノーシスの部位に一致して1型腫瘍を認めた。生検にて食道原発悪性黒色腫と診断された。cT2N0M0、Stage II(食道癌取扱い規約第11版)であったため、根治的な食道切除術を施行した。術後1年6ヵ月のCT検査で肝転移を認め、一次治療としてnivolumabによる免疫療法を施行中である。食道メラノーシスに対しては食道原発悪性黒色腫の発症を念頭に置いた注意深い経過観察が必要である。(著者抄録)

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Language：Japanese   Publisher：(株)癌と化学療法社  

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Language：Japanese   Publisher：(株)癌と化学療法社  

症例は77歳、女性。56歳時に膵腫瘍に対し尾側膵切除を施行され、病理組織学的検査で膵神経内分泌腫瘍(p-NET)G2と診断された。膵切除10年後に肝S6転移に対し肝右葉切除を施行された。初回肝切除8年後に肝S4転移を認め、ラジオ波焼灼療法(RFA)を施行されたが、肝内に血腫を形成して中止された。RFA施行6ヵ月後に肝S4部分切除を施行された。RFA施行2年後に右横隔膜下に限局性腹膜播種再発を認め、開胸を伴う右横隔膜合併切除を行い、病変を一括切除した。播種切除後2年が経過し、無再発生存中である。p-NETの限局性腹膜播種再発では他部位に再発巣がなく、根治切除が可能であれば外科切除が生存期間の延長に寄与する可能性がある。(著者抄録)

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A 77-year-old woman presented with peritoneal metastases from a pancreatic neuroendocrine tumor(p-NET). At the age of 56 years, she underwent distal pancreatectomy for p-NET, which was pathologically diagnosed as G2. She underwent right hemihepatectomy for liver metastasis(S6)from the p-NET 10 years post-pancreatectomy. Eight years post-hepatectomy, radiofrequency ablation(RFA)was attempted for liver metastasis(S4)from the p-NET. However, RFA was not completed because of hematoma development along the needle tract of RFA. She underwent partial hepatectomy for this lesion 6 months post-RFA. Two years post-RFA, localized peritoneal metastases on the right diaphragm were detected. She underwent en bloc tumor resection with partial resection of the diaphragm. She remains alive and well with no evidence of disease 2 years post-resection of the peritoneal metastases from the p-NET.

PubMed

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Language：Japanese   Publishing type：Research paper (scientific journal)  

A 37-year-old man was admitted to our hospital for the treatment of familial adenomatous polyposis and rectal carcinoma. He underwent total colectomy with ileoanal anastomosis(pT3N1M0, pStage Ⅲa)followed by adjuvant therapy with S-1. Three months after primary surgery, CT and MRIrevealed liver metastases(S5, S6). Laparoscopic partial hepatectomy was performed. Two years after primary surgery, new liver metastases(S2, S8)were found and we performed open partial hepatectomy and administered mFOLFOX6. Three years and 5 months after primary surgery, right lung metastases(S6, S9) were detected and the patient underwent a thoracoscopic-assisted right lung wedge resection. Repeated resection of metastases might have contributed to the long-survival in our case.

PubMed

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Language：Japanese   Publisher：(株)癌と化学療法社  

症例は37歳、男性。家族性大腸腺腫症および直腸癌、cT3N0M0、cStage IIの診断で、大腸全摘、回腸嚢肛門吻合、D3リンパ節郭清術を施行した。病理組織学的診断の結果は直腸癌、pT3N1M0、pStage IIIaであったため、術後補助化学療法としてS-1の内服を開始した。術後3ヵ月目に肝転移(S5、S6)を認め、腹腔鏡下肝部分切除術を施行した。術後24ヵ月後、肝転移再発(S2、S8)を認め、開腹肝部分切除術を施行した。術後41ヵ月後、右肺S6、S9に転移を認め、胸腔鏡補助下肺部分切除術(S6、S9)を行った。転移巣に対し外科的切除を行い、長期生存を得られている家族性大腸腺腫症に伴う直腸癌の1例を経験した。複数回の肝転移切除術、肺転移切除術の意義を示す症例として報告する。(著者抄録)

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背景:婦人科悪性腫瘍に対して、婦人科医と消化器外科医による合同手術がしばしば行われているが、その術後成績については明らかでない。目的:婦人科悪性疾患手術時に消化器外科医が介入した症例について、術式、合併症、予後などの術後成績を明らかにすることを目的とした。対象と方法:2010年1月〜2014年12月までの5年間の73例を対象とした。疾患、術式、術後合併症、ストーマの有無、入院期間、予後などを検討した。結果:年齢中央値(範囲)は60(15〜78)歳、73例全例が女性であった。緊急手術が8例(11.0%)含まれていた。疾患は、卵巣癌が56例(76.7%)と最も多く、Stageの内訳はStage I/II/III/IV/再発:4/4/20/11/17例であった。25例(34.2%)で腸管切除吻合が行われていた。また、22例(30.1%)でストーマが造設されていたが、本検討ではストーマ閉鎖を行えた症例はなかった。手術時間(婦人科原発巣手術時間も含む)中央値(範囲)は252(37〜690)分であり、出血量は1,190(0〜11,210)mLであった。術後の合併症(Clavien-Dindo II以上)として、イレウス6例(8.2%)、腹骨盤内膿瘍4例(5.5%)、縫合不全2例(2.7%)などがみられた。Grade III以上の合併症としてはイレウス、縫合不全、腹水、膵液瘻がそれぞれ1例ずつ認められた。卵巣癌全症例の術後生存期間中央値は1,399日であった。結論:婦人科との合同手術のなかで、消化器外科医は進行卵巣癌の手術に携わることが多い。ストーマを造設した症例のストーマ閉鎖は困難であるが、消化管切除を含む腫瘍切除によって予後の延長に寄与することが期待される。(著者抄録)

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症例は62歳、男性。主訴は血便。下部消化管内視鏡検査で、下部直腸に5cm大の直腸癌が指摘された。組織型は高分化管状腺癌であり、腫瘍下縁は肛門管近傍まで達していた。腹部骨盤部造影CT検査で直腸間膜リンパ節転移が指摘され、進行直腸癌(cT3N1P0M0、Stage IIIa、大腸癌取扱い規約第8版)と診断された。本人が肛門温存を希望したため、前医で術前化学療法の方針となった。化学療法としてcapecitabine、oxaliplatin(CapeOX)+bevacizumab(BV)療法が12コース施行された。化学療法後の下部消化管内視鏡検査で腫瘍は著明に縮小し、肉眼的には厚みのある瘢痕のみとなっていた。瘢痕からの生検では悪性所見を認めなかった。しかし画像検査で直腸壁の肥厚は残存していたため、化学療法の効果判定はpartial response(縮小率40%)、ycT3N0M0、ycStage IIと診断した。肛門温存手術が可能と判断して、括約筋間直腸切除術、一時的回腸人工肛門造設術を施行した。切除標本の組織診断では主病巣に悪性細胞を認めず、リンパ節転移も陰性であった。原発巣切除後6ヵ月目に小腸人工肛門閉鎖術を施行した。術後追加治療を行わずに外来で経過観察中であるが、再発の所見は認めていない。CapeOX+BV療法によって組織学的完全奏効が得られた進行下部直腸癌の1例を経験したので報告する。(著者抄録)

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症例は65歳、女性。便潜血陽性のため下部消化管内視鏡検査が施行され、直腸S状部に2cm大のtype 0-IIa病変(組織型はtub2、por)、上部直腸に6cm大の5型病変(組織型はmuc、sig、tub2)が指摘された。胸腹骨盤部CT検査、PET-CT検査で腸管傍リンパ節転移陽性と診断された。直腸間膜リンパ節、大動脈周囲リンパ節、側方リンパ節領域にも淡いfluorodeoxyglucose集積を認めた。転移の可能性も否定できなかったが、直腸S状部癌cT1bN0M0、Stage I、上部直腸癌cT3N1M0、Stage IIIa(大腸癌取扱い規約第8版)と診断した。腎機能障害により化学療法の選択に制限があったため手術先行の方針とし、低位前方切除術を施行した。術中、大動脈周囲リンパ節、左総腸骨動脈リンパ節を迅速診断に提出し、リンパ節転移陽性と診断された。リンパ節以外に遠隔転移を認めなかったことからR0切除が可能と判断し、転移陽性であった領域のリンパ節は可及的に切除した。切除標本の組織診断では、直腸S状部の病変は深達度T1b、上部直腸病変は深達度T3であった。切除リンパ節37個中21個で転移陽性であった。RAS遺伝子検査では野生型であった。補助化学療法としてS-1単剤療法を施行した。術後5ヵ月目と3年目に縦隔リンパ節転移が疑われたためpanitumumab単剤療法を行ったところ、リンパ節腫大は縮小した。現在、初回手術から6年が経過したが直腸癌再発は認めていない。長期生存が得られている大動脈周囲リンパ節、側方リンパ節への転移を伴った進行直腸癌の1例を経験したので報告する。(著者抄録)

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Language：Japanese   Publisher：(一社)日本内視鏡外科学会  

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症例は66歳、男性。右頸部に腫瘤を自覚し、精査にて48×34mm大の右鎖骨上リンパ節転移を伴う胸部中部食道扁平上皮癌、cT2N2M0、cStage IIIと診断された。術前docetaxel/cisplatin/5-FU(DCF)療法を3コース施行され、部分奏効と判定された。手術は胸腔鏡下食道切除術、3領域リンパ節郭清、胸骨後経路胃管再建を施行された。術後病理組織学的診断にて原発巣および右鎖骨上リンパ節転移巣ともに腫瘍細胞の遺残を認めず、組織学的完全奏効と判定された。進行食道癌に対する術前DCF療法は高い組織学的完全奏効割合から新規術前化学療法として有望である。(著者抄録)

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：English   Publisher：(一社)日本癌治療学会  

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Language：Japanese   Publisher：日本臨床外科学会  

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Language：Japanese   Publisher：日本臨床外科学会  

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Language：Japanese   Publisher：日本臨床外科学会  

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Language：Japanese   Publisher：日本臨床外科学会  

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Language：Japanese   Publisher：日本臨床外科学会  

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Language：English   Publisher：(一社)日本癌治療学会  

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Language：Japanese   Publisher：日本臨床外科学会  

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Language：English   Publisher：(一社)日本癌治療学会  

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Language：English   Publisher：(一社)日本癌治療学会  

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Language：Japanese   Publisher：(一社)日本大腸肛門病学会  

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Language：English   Publisher：(一社)日本癌学会  

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PURPOSE: Treatment strategies of rectal cancer differ between tumors located above (RS/Ra) and below (Rb) the peritoneal reflection. Based on the extent of distal spread (DS), the Japanese Society for Cancer of Colon and Rectum proposed an optimal distal margin in RS/Ra and Rb tumors. In this study, we investigated the clinical significance of DS between RS/Ra and Rb tumors. METHODS: We analyzed 287 stage I-III rectal cancer patients who underwent curative intent resection without preoperative therapy. DS and other pathological factors were evaluated using whole-mount sections. To investigate the clinical significance of DS in RS/Ra and Rb tumors, clinicopathological variables, including DS, were analyzed for the survival outcome according to the tumor group. RESULTS: DS was detected in 20 out of 185 (11%) patients with RS/Ra tumors and 8 out of 102 (8%) patients with Rb tumors. DS was not significantly associated with the overall survival (OS) or relapse-free survival (RFS) in RS/Ra tumors, but was an independent prognostic factor for the OS and RFS in Rb tumors (P = 0.002 and 0.007, respectively). CONCLUSIONS: The clinical significance of DS differs between RS/Ra and Rb tumors. DS is associated with a worse survival in Rb tumors, but not in RS/Ra tumors.

DOI： 10.1007/s00595-019-01882-x

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Language：English   Publisher：(一社)日本癌学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(株)癌と化学療法社  

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Language：Japanese   Publisher：日本消化器病学会-甲信越支部  

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BACKGROUND: The Memorial Sloan Kettering Cancer Center (MSK) colon cancer recurrence nomogram is a risk calculator that provides patients and clinicians with individualized prediction of recurrence following curative resection of colon cancer. Although validated on multiple separate cohorts, the nomogram requires periodic updating as patient care changes over time. The aim of this study was to evaluate the nomogram's accuracy in a contemporary cohort and modify the tool to reflect improvements in outcome related to advances in colon cancer therapy. METHODS: A contemporary patient cohort was compiled, including consecutive colon cancer patients undergoing curative resection for stage I-III colon adenocarcinoma at MSK from 2007 to 2014. The nomogram's predictive accuracy was assessed by concordance index and calibration plots of predicted vs actual freedom from recurrence at 5 years after surgery. RESULTS: Data from a total of 999 eligible patients with complete records were used for validation. Median follow-up among survivors was 37 months. The concordance index was 0.756 (95% confidence interval = 0.707 to 0.805), indicating continued discriminating power, but the calibration plot revealed that the nomogram overestimated recurrence risk. Recalibration of the nomogram by estimating a new baseline freedom-from-recurrence function restored the nomogram's accuracy. CONCLUSION: The updated nomogram retains the original nomogram's variables but includes a lower baseline estimation of recurrence risk, reflecting improvements in outcomes for all stages of colon cancer, likely resulting from advances in imaging and integration of multiple treatment modalities.

DOI： 10.1093/jncics/pkz015

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Language：Japanese   Publisher：(一社)日本大腸肛門病学会  

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Language：Japanese   Publisher：(一社)日本大腸肛門病学会  

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AIMS: SMAD4 acts as a tumour suppressor, and the loss of SMAD4 is associated with poor prognosis in colorectal cancer (CRC) patients. Although next-generation sequencing (NGS) enabled us to detect numerous genetic alterations in a single assay, the clinical significance of SMAD4 alteration detected with NGS has not been fully investigated. The aim of this study was to evaluate the clinicopathological characteristics and clinical significance of SMAD4 alteration detected with NGS in CRC. METHODS AND RESULTS: We retrospectively investigated 201 patients with stage I-IV CRC, by using a 415-gene panel. To analyse the relationship between SMAD4 alteration and other clinicopathological characteristics, we evaluated clinicopathological variables, including invasive-front pathological markers: tumour budding, poorly differentiated cluster, and Crohn-like lymphoid reaction. Fifty-six patients (28%) had SMAD4 alteration: 24 and 32 patients had SMAD4 mutation and deletion, respectively. SMAD4 alteration was significantly associated with T category (P = 0.027), N category (P = 0.037), M category (P = 0.028), and invasive-front pathological markers, such as poorly differentiated cluster grade 3 (P = 0.020) and absence of Crohn-like lymphoid reaction (P = 0.004). Immunohistochemistry revealed that SMAD4 alteration was significantly associated with loss of SMAD4 (P = 0.023). In 90 patients with stage I-III disease, SMAD4 alteration was significantly associated with poor prognosis for relapse-free and overall survival (P = 0.047; P = 0.022, respectively). Conversely, in 111 patients with stage IV disease, SMAD4 alteration was not significantly associated with overall survival. CONCLUSION: SMAD4 alteration is associated with invasive-front pathological markers and poor prognosis in stage I-III CRC patients.

DOI： 10.1111/his.13805

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Language：Japanese   Publisher：(一社)日本大腸肛門病学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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BACKGROUND: Surgical stress and inflammation can cause hyperbilirubinemia, which sometimes occurs after esophagectomy for esophageal cancer (EC). The aim of this study was to elucidate the clinical significance of postoperative hyperbilirubinemia in the management of EC patients. MATERIALS AND METHODS: We retrospectively reviewed records of 81 EC patients who underwent esophagectomy from 2009 to 2014. We compared the clinicopathological and perioperative factors, including the presence of hyperbilirubinemia (total bilirubin ≥1.5 mg/dL), between patients with postoperative infectious complications (PIC group) and those without (Non-PIC group). RESULTS: PIC developed in 52 patients (64.2%). There were significant differences in incidence of postoperative hyperbilirubinemia between the PIC group and the non-PIC group (34.6% vs. 3.4%, P = 0.002), as well as the approach of esophagectomy (P = 0.045), the surgical duration (469 vs. 389 min, P < 0.001), the amount of blood loss (420 vs. 300 mL, P = 0.018), the frequency of intraoperative blood transfusions (32.7% vs. 6.9%, P = 0.012) and the peak postoperative C-reactive protein level (17.3 vs. 8.6 mg/dL, P = 0.007). Multivariate analysis revealed hyperbilirubinemia was independently associated with the occurrence of PICs (odds ratio: 38.6, P = 0.010). The median time to the diagnosis of hyperbilirubinemia was significantly shorter than that of PICs (3.0 vs. 4.5 days, P = 0.025). CONCLUSIONS: Postoperative hyperbilirubinemia was associated with the occurrence of PICs and frequently occurred before any PICs become apparent. More attention should be paid to the serum bilirubin level in the management after esophagectomy for EC.

DOI： 10.1016/j.amsu.2019.02.004

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Language：Japanese   Publisher：(株)癌と化学療法社  

症例は78歳、女性。黄疸を主訴に来院した。ウイルス性肝炎は陰性で、AFP 925ng/mL、PIVKA-II 6,820mAU/mLはともに上昇していた。CT検査で肝S1に径3cm大の腫瘍と、これより連続して右肝管内に至る胆管内腫瘍栓を認めた。胆管内腫瘍を伴う肝細胞癌と診断し、減黄を図りつつ肝動脈化学塞栓療法を実施後に肝左葉切除、尾状葉切除、肝外胆管切除を実施した。胆道鏡検査で胆管内腫瘍栓の右肝管への浸潤が疑われ、右前・後区域胆管合流部直下で胆管を切離した。病理組織学的には中分化型肝細胞癌で胆管内腫瘍栓を認めたが、血管侵襲陰性、切離断端陰性であった。術後5年4ヵ月が経過し、無再発生存中である。自験例の経験および文献的考察から、根治切除が可能な胆管内腫瘍栓を伴う肝細胞癌では長期生存が得られる症例が存在するので、肝切除を考慮するべきである。(著者抄録)

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Language：Japanese   Publishing type：Research paper (scientific journal)  

A 78-year-old woman with jaundice was referred to our hospital. On admission, serological testing for viral hepatitis was negative and serum levels of AFP and PIVKA-Ⅱ were elevated(925 ng/mL and 6,820 mAU/mL, respectively). Computed tomography revealed a main tumor measuring 3 cm in size at segment 1 of the liver and bile duct tumor thrombus extending to the right hepatic duct. A diagnosis of hepatocellular carcinoma with a bile duct tumor thrombus was made. After endoscopic biliary drainage for obstructive jaundice and transarterial chemoembolization for the lesions, she underwent left hepatectomy, resection of the caudate lobe, extrahepatic bile duct resection, and cholecystectomy. The hepatic side of the extrahepatic bile duct was transected at the confluence of the right anterior and posterior ducts because invasion of the tumor thrombus to the right hepatic duct was suspected on cholangioscopy. Histological examination revealed the tumor to be a moderately differentiated hepatocellular carcinoma with bile duct tumor thrombus. Surgical margins were negative, and vascular invasion was not found. She remains alive and well with no evidence of disease 64 months after hepatectomy.

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症例は82歳、男性。検診を契機に診断された膵管内乳頭粘液性腫瘍で、亜全胃温存膵頭十二指腸切除術を施行した。病理診断は膵管内乳頭粘液性腺癌で、pT3N1M0、pStage IIBであった。術後補助化学療法としてS-1療法を行っていたが、術後6ヵ月で上腹部痛の訴えがあり、CT検査で腹壁および腹膜播種再発と診断した。化学療法の適応であるが、高齢であり再発部位は上腹部に限局していたため、症状緩和治療を行うこととした。オピオイドを導入し、局所に対して30Gyの緩和的放射線療法を行った。癌性疼痛は軽快しオピオイドの離脱が可能であった。再発から2ヵ月後にnab-paclitaxel+gemcitabine併用療法を開始した。放射線療法によって症状は緩和され、化学療法にて病状の進行は抑制され、QOLを維持できている。術後2年6ヵ月現在、再発から2年経過しているが無増悪生存中である。(著者抄録)

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Language：Japanese   Publishing type：Research paper (scientific journal)  

An 82-year-old man with a diagnosis ofintraductal papillary mucinous carcinoma(IPMC)underwent pancreaticoduodenectomy followed by adjuvant chemotherapy with S-1. Six months after surgery, he had upper abdominal pain, and CT demonstrated a recurrent intraabdominal tumor located at the surgical incision scar. It was diagnosed as a solitary peritoneal recurrence, and palliative radiation therapy at a dose of 30 Gy was performed for the relief of abdominal pain after administration ofoxycodone. He was free ofpain without pharmacological therapy and received subsequent chemotherapy with nabpaclitaxel plus gemcitabine(GnP). He remains free ofpain and alive without progression ofthe disease 24 months after recurrence. Hypofractionated-accelerated radiotherapy is feasible and results in pain relief for local recurrence of IPMC.

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Numerous technical and functional advances in next-generation sequencing (NGS) have led to the adoption of this technique in conventional clinical practice. Recently, large-scale genomic research and NGS technological innovation have revealed many more details of somatic and germline mutations in solid tumors. This development is allowing for the classification of tumor type sub-categories based on genetic alterations in solid tumors, and based on this information, new drugs and targeted therapies are being administered to patients. This has largely been facilitated by gene panel testing, which allows for a better understanding of the genetic basis for an individual's response to therapy. NGS-based comprehensive gene panel testing is a clinically useful approach to investigate genomic mechanisms, including therapy-related signaling pathways, microsatellite instability, hypermutated phenotypes, and tumor mutation burden. In this review, we describe the concept of precision medicine in solid tumors using NGS-based comprehensive gene panel testing, as well as the importance of quality control of tissue sample handling in routine NGS-based genomic testing, and we discuss issues for the future adoption of this technique in Japan.

DOI： 10.1007/s10147-018-1375-3

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Comprehensive genomic sequencing (CGS) enables us to detect numerous genetic alterations in a single assay. We aimed to identify molecular markers for predicting prognosis and conversion surgery in Stage IV colorectal cancer (CRC) using CGS. One-hundred eleven patients with Stage IV CRC who underwent primary tumor resection were analyzed. We retrospectively investigated genetic alterations using CGS of a 415-gene panel. Clinicopathological variables and genetic alterations were analyzed to identify independent prognostic factors of overall survival (OS). Forty-five of 111 patients had R0 resection; of these, 11 patients underwent conversion surgery. Univariate and multivariate analyses identified histopathological grade 3, R0 resection, BRAF V600E mutation, and SRC mutation as independent prognostic factors for OS (P = 0.041, P = 0.013, P = 0.005, and P = 0.023, respectively). BRAF V600E and SRC mutations were mutually exclusive, and SRC mutation was significantly associated with left-sided tumor and liver metastasis compared to BRAF V600E mutation (P = 0.016 and P = 0.025, respectively). Eleven of the 74 initially unresectable patients underwent conversion surgery for R0 resection, yet none harbored BRAF V600E or SRC mutations. BRAF V600E and SRC mutations are important molecular markers which can predict prognosis and conversion surgery in Stage IV CRC.

DOI： 10.1038/s41598-019-39328-6

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BACKGROUND/OBJECTIVE: Restorative proctocolectomy (RP) may improve quality of life in patients with ulcerative colitis (UC)-associated lower rectal cancer to a greater extent than total proctocolectomy. However, patients with UC-associated cancer often have flat mucosal lesions that make it extremely difficult to endoscopically delineate the tumor margins. Therefore, there is a potential risk of residual tumor and local recurrence after RP in patients with UC-associated lower rectal cancer. The aim of this study was to assess the feasibility of RP in patients with UC-associated cancer of the lower rectum. METHODS: We retrospectively identified nine patients who had undergone RP for UC-associated lower rectal cancer at the Niigata University Medical and Dental Hospital between January 2000 and December 2016. The incidence of flat mucosal cancer, distal margin status, and oncologic outcomes were evaluated in the nine patients. RESULTS: Eight (89%) of the nine patients had flat mucosal cancer in the lower rectum. The median length of the distal margin was 22 mm (range 0-55 mm). No patient developed local or distant recurrence during follow-up. One patient had a positive distal margin. This patient underwent annual pouchoscopy, but had no local recurrence and died of pancreatic cancer 81 months after RP. The remaining eight patients were alive at the final observation. Five-year and 10-year overall survival rates in the nine patients were 100% and 66.7%, respectively. CONCLUSION: Patients with UC-associated lower rectal cancer often have lesions of the flat mucosal type. However, RP is feasible and not necessarily contraindicated in such patients.

DOI： 10.1016/j.asjsur.2018.01.003

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BACKGROUND: Neurofibromatosis type 1 (NF1) is an autosomal dominant disease of the skin and soft tissue. Aneurysms associated with NF1 can occur, but a secondary aneurysm rupture is very rare, with very few cases reported in literature. CASE PRESENTATION: We describe the case of a 67-year-old female with NF1 who underwent endovascular aneurysm repair (EVAR) for an abdominal aortic aneurysm (AAA) rupture. She developed a type Ib endoleak requiring a redo-EVAR. Eighteen days after her primary operation, she was found to have two new left colic artery aneurysms. She required emergency surgery consisting of a left hemicolectomy and transverse colon colostomy. Pathology showed neurofibromatous changes to the peri-vasculature tissue, consistent with her underlying disease. CONCLUSIONS: Although rare, secondary aneurysms can occur following AAA repair. Patients with soft tissue connective tissue disorders, like NF1, may be at an increased risk for development of these secondary aneurysms. Endovascular repair appears to be a safe approach for NF1 patients with AAA, but endovascular management can be challenging in the setting of NF1. Surgeons should be ready to convert to open surgery if the patient displays persistent signs of bleeding or structural changes related to connective tissue disorders like NF1.

DOI： 10.1186/s40792-019-0570-4

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Language：Japanese   Publisher：(株)癌と化学療法社  

症例は59歳、女性。心窩部痛を主訴に発症し、精査にて切除可能膵頭部癌と診断された。幽門輪温存膵頭十二指腸切除術を施行した。病理所見は高分化型管状腺癌で、細胞質に粘液成分を多く含む核異型の軽度な腫瘍細胞を主体としていた。最終診断は膵頭部癌、pT3N0M0、Stage IIAであった。術後、肝灌流療法として5-FUの肝動注・門脈注を行い、引き続きgemcitabineでの術後補助化学療法を1年間施行した。術後7年目のCT、PET-CTで左頸部リンパ節転移が疑われた。全身検索では他臓器癌を認めなかった。診断を兼ねて再切除の方針となり、左頸部リンパ節摘出術を行った。病理組織は初回切除時の原発巣と同様な組織像を呈する豊富な粘液産生を伴う高分化型腺癌であり、膵癌の再発として矛盾しなかった。術後はS-1単独療法を約1年間行った。現在は再切除から3年10ヵ月無再発生存中であり、初回手術から11年の長期生存を得ている。(著者抄録)

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肝細胞癌(HCC)の腹膜播種はまれであり、これに対する外科切除の治療効果に関しては一定の見解が得られていない。症例1:48歳、男性。肝S6のHCCに対し二度の肝切除、一度のラジオ波焼灼療法(RFA)が施行された。初回手術から8年後に骨盤底に腹膜播種を来し外科切除が施行された。腹膜播種切除後17ヵ月が経過し再発生存中である。症例2:71歳、男性。肝S6のHCCに対して三度の穿刺局所療法が施行され、残肝局所再発に対し手術が施行された。腫瘍近傍に腹膜播種を認め同時切除が行われたが、骨盤内再発を認めて腹膜播種切除後20ヵ月目に原病死した。症例3:58歳、男性。肝S6のHCCに対する肝S6亜区域切除後8年目に十二指腸狭窄を伴う腹膜播種が認められた。外科切除を施行したが、その2ヵ月後に原病死した。文献的考察や自験例の経験から、HCC腹膜播種(少数個)に対して外科切除は有効な治療選択肢の一つになり得る。(著者抄録)

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BACKGROUND: Recent advances in next-generation sequencing have enabled the detection of BRAF V600E mutations as well as BRAF non-V600E mutations in a single assay. The present work aimed to describe the clinicopathological characteristics and clinical outcome of the BRAF non-V600E mutant-type in colorectal cancer (CRC). PATIENTS AND METHODS: CRC samples from 111 Stage IV patients were analyzed for somatic mutations using a 415-gene comprehensive genomic sequencing panel. Patients were classified according to BRAF status as wild-type, V600E mutant-type, or non-V600E mutant-type. Differences between clinicopathological characteristics and genetic alterations were analyzed among the three groups. Overall survival (OS) and the response to anti-EGFR therapy were also analyzed. RESULTS: Comprehensive genomic sequencing revealed that 98 patients (88%), 7 patients (6%), and 6 patients (6%) were wild-type, V600E mutant-type, and non-V600E mutant-type, respectively. Non-V600E mutant-type tumors were frequently left-sided (83%), while V600E mutant-type tumors were frequently right-sided (86%; P = 0.025). Non-V600E mutant-type showed better OS than V600E mutant-type (P = 0.038), with no significant difference compared with wild-type tumors. The two patients with non-V600E mutations who underwent repeated metastasectomies showed no evidence of disease at final follow-up. Regarding the efficacy of anti-EGFR therapy, the patient with an I326V mutation had progressive disease (+115%) despite no genetic alterations detected in the EGFR pathway that could drive resistance, suggesting an alternate resistance mechanism. CONCLUSIONS: Non-V600E mutant-type is more likely to be left-sided and demonstrates better OS than V600E mutant-type. Further preclinical and clinical investigations are needed to clarify the role of non-V600E mutations in CRC.

DOI： 10.1016/j.jss.2018.06.020

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A 59-year-old woman with pancreatic cancer underwent pancreaticoduodenectomy. The tumor was histologically diagnosed as a well-differentiated tubular adenocarcinoma with a small amount of mucinous component. After resection, the patient underwent hepatic perfusion therapy using 5-FU and gemcitabine chemotherapy for 1 year. 7 years after the initial surgery, CT and PET-CT revealed an isolated enlarged lymph node in the left neck. As the patient had no other metastasis, lymphadenectomy was performed. A diagnosis of lymph node metastasis originating from pancreatic cancer was confirmed on the basis of histological and immunohistopathological assessments. After the second resection, chemotherapy with S-1 was administered for 1 year. The patient has been alive without tumor relapse for 11 years. In patients with late recurrence after pancreatectomy, aggressive isolated lymph node resection and maintained chemotherapy may contribute to the improvement in prognosis.

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We present a case of long-term survival in a patient with advanced ascending colon cancer and multiple liver metastases after receiving multimodality therapy, which included hepatic atrial infusion(HAI)and 4 hepatectomies. At diagnosis, the 65- year-old woman underwent right hemicolectomy for advanced ascending colon cancer with multiple liver metastases (T3N1M1[H2], Stage Ⅳ). The 11 liver metastatic lesions were treated by weekly HAI of 5-fluorouracil(5-FU). The lesions reduced in size(response rate 28.9%)immediately following treatment, and no new lesions were detected, but 10 months after treatment the size of the S2 tumor had increased. Systemic chemotherapy with irinotecan and S-1 was administered. Continued development of the S2 tumor in the liver prompted a radical lateral segment hepatectomy. Four months later, a computed tomography(CT)scan revealed a S6 tumor of the liver, for which a posterior segment hepatectomy was performed. A CT scan showing a S1 tumor in the liver 9 months later resulted in chemotherapeutic treatment with CapeOX, followed by mFOLFOX6. Despite treatment, the S1 tumor developed further, prompting a S1 partial hepatectomy. A further partial S8 hepatectomy was performed 7 years after surgery for the primary lesion following a CT scan that revealed a S8 tumor in the liver. There has been no recurrence of tumors in the 5 years and 5 months since this last hepatectomy.

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Language：Japanese   Publishing type：Research paper (scientific journal)  

Here, we reported a case of a 39-year-old woman having rectal cancer with multiple liver metastases who underwent staged laparoscopic resection. She was diagnosed with low rectal cancer and multiple liver metastases; thus, she underwent low anterior resection and diverting colostomy. Following the neoadjuvant chemotherapy, she underwent colostomy closure and subsequent hand-assisted laparoscopic partial hepatectomy using the operative site during the colostomy closure. The postoperative course was uneventful, and adjuvant chemotherapy with CapeOX was performed 3 weeks post-surgery. Minimally invasive surgery was performed using hand-assisted laparoscopy.

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Language：Japanese   Publishing type：Research paper (scientific journal)  

Peritoneal metastasis is relatively rare in patients with hepatocellular carcinoma(HCC). No consensus has been reached regarding the treatment of this type of metastasis. Herein, we report 3 patients who underwent resection of peritoneal metastasis due to HCC. Case 1: A 48-year-old man underwent hepatectomy twice and radiofrequency ablation(RFA)once for HCC. Eight years after the initial resection, he underwent resection of peritoneal metastasis in the pelvic floor. He is alive with disease 17 months after the last operation. Case 2: A 71-year-old man with a history of percutaneous ablation therapy for HCC 3 times underwent hepatectomy for recurrent HCC. During the laparotomy, a peritoneal metastatic tumor was found near the live tumor, and simultaneous resection of both the tumors was performed. The patient died of recurrent disease 20 months after the last resection. Case 3: A 58-year-old man underwent hepatectomy for HCC and RFA for its recurrence. Peritoneal metastasis that invaded the duodenum was detected 8 years after the hepatectomy. Although the metastatic tumor was resected, he died of the carcinoma 2 months after the resection. We concluded that resection of peritoneal metastasis provides a survival benefit for selected patients with HCC.

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Language：Japanese   Publishing type：Research paper (scientific journal)  

A 78-year-old man was admitted with diarrhea. Colonoscopy and computed tomography(CT)revealed rectal cancer with multiple liver metastases. Low anterior resection was performed for local control. After the operation, 5 courses of mFOLFOX6 plus bevacizumab chemotherapy were administered as first-line systemic therapy, but CT showed progressive disease with liver metastases. After the first-line systemic therapy, 2 courses of FOLFIRI plus bevacizumab chemotherapy were performed as second-line systemic therapy, but CT also revealed progressive disease with liver metastases. We retrospectively performed comprehensive genomic sequencing with a 415-gene panel and found that the patient had a hypermutation subtype. Interestingly, the panel also revealed that he had mismatch-repair(MMR)deficiency with MSH2 mutation, which is reported as a possible cause of resistance to 5-fluorouracil in colorectal cancer.

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Language：Japanese   Publisher：(株)癌と化学療法社  

症例は65歳、女性。同時性肝転移を伴う上行結腸癌[T3N1M1(H2)、Stage IV]と診断し、結腸右半切除術を施行した。11個の肝転移に対して、5-FU肝動注療法を施行した。縮小率28.9%と奏効していたが、10ヵ月施行時に肝S2の病変が増大した。全身化学療法としてIRIS療法を施行したが奏効せず、拡大肝外側区域切除を施行した。さらに4ヵ月後、肝S6の再発病変に対して肝後区域切除を施行した。その9ヵ月後に肝S1の肝転移巣を指摘され、CapeOX、mFOLFOX6療法を施行したが、標的病変が増大し、肝S1部分切除を施行した。さらに4ヵ月後、肝S8に再発を来し、肝S8部分切除を行った(原発巣切除術後7年)。以後5年5ヵ月、再発を認めていない。本症例は分子標的薬導入以前の症例であり、肝動注療法、全身化学療法、4回の肝切除を行うことで12年5ヵ月の長期生存を得た。大腸癌肝転移に対する肝動注療法、複数回肝切除の意義を示す症例として報告する。(著者抄録)

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Language：Japanese   Publisher：(株)癌と化学療法社  

症例は78歳、男性。下痢を主訴に受診し、肝転移を伴う直腸癌と診断された。術中所見で肝転移は切除不能と診断され、局所制御のため超低位前方切除術を施行した。術後にmFOLFOX6+bevacizumab療法を5コース、FOLFIRI+bevacizumab療法を2コース施行したが、どちらも奏効しなかった。後方視的に施行した次世代シークエンサーによる遺伝子変異解析パネル検査(415遺伝子)では、原発巣に高頻度の体細胞変異を有するhypermutationであったことが判明した。大腸癌におけるhypermutationの多くはミスマッチ修復遺伝子の異常を有し、5-fluorouracil系抗癌剤が無効である可能性がある。一方で、免疫チェックポイント阻害薬が有効である可能性がある。薬物療法前に遺伝子変異解析パネル検査を行うことで、個々の患者に最適な治療法を提案できる可能性が示唆された。(著者抄録)

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Language：Japanese   Publisher：(株)癌と化学療法社  

切除可能な遠隔転移を有する大腸癌は、原発巣に加えて遠隔転移巣に対するR0切除が推奨されている。症例は39歳、女性。血便を主訴に近医を受診した。大腸内視鏡検査を施行し、上部直腸癌と診断した。また、腹部MRI検査を施行し、肝S4およびS5/8に計2個の肝転移を認めた。二期的切除の方針とし、一期目の手術として腹腔鏡補助下低位前方切除術、横行結腸双孔式人工肛門造設術を施行した。肝転移に対する術前補助化学療法としてCapeOX療法を2コース施行した後に、二期目の手術として人工肛門閉鎖術と人工肛門閉鎖創を利用した用手補助腹腔鏡下肝部分切除術の同時手術を施行した。術後経過は良好で、二期目の手術から21日後にCapeOX療法を再開した。人工肛門閉鎖の創部を利用して用手補助用デバイスを装着し、安全かつ低侵襲に肝部分切除を施行できたと考える。(著者抄録)

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Academic Press Inc.  

Background: Colitis-associated cancer (CAC) is the most serious complication of inflammatory bowel disease. Sphingosine-1-phosphate (S1P) is a bioactive lipid mediator that is generated by sphingosine kinase 1 (SphK1) and is known to play an important role in inflammation and cancer progression. Moreover, SphK1 and S1P act as upstream mediators of proinflammatory cytokine interleukin 6 (IL-6) and signal transducer and activator of transcription-3 (STAT3). We hypothesized that the expression levels of phosphorylated SphK1 (pSphK1), phosphorylated STAT3 (pSTAT3), and IL-6 are universally higher in CAC patients than in sporadic colorectal cancer (CRC) patients because all of these factors are associated with inflammation. In this study, we determined the expression levels of pSphK1 in patients with sporadic CRC and CAC and clarified the importance of S1P in CAC patients. Materials and methods: We randomly selected 10 sporadic CRC patients and 10 CAC patients who underwent curative resection, and we examined their surgical specimens by immunohistochemistry. We determined the expression levels of pSphK1, pSTAT3, and IL-6 in these samples. Results: We found pSphK1 expression to be more prevalent in CAC patients (P = 0.019) and to have a higher immunohistochemistry score (P = 0.005) than in sporadic CRC patients. However, the expression of pSTAT3 and IL-6 did not differ between the patient groups. Conclusions: To our knowledge, this is the first report comparing pSphK1 expression levels in CAC with those in sporadic CRC. The high levels of pSphK1 expression in CAC suggest an important role of S1P in the disease process of CAC.

DOI： 10.1016/j.jss.2018.05.085

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(株)南江堂  

＜文献概要＞次世代シークエンサーを用いた癌遺伝子パネル検査によって,RAS/RAF遺伝子をはじめとする薬剤耐性関連の遺伝子変異や,HER2遺伝子増幅などの治療標的の候補となる遺伝子変異の網羅的検索が大腸癌において可能となる.今後の遺伝子解析に備え,手術や生検組織検体の適切な保存について熟知しておくことが重要である.Lynch症候群の大腸癌はマイクロサテライト不安定性を呈し,免疫チェックポイント阻害薬が有効である可能性が示唆され注目を集めている.癌遺伝子パネル検査の普及によって,Lynch症候群などの遺伝性腫瘍と診断される症例が今後増加することが予想され,遺伝カウンセリングやサーベイランスなどの患者,家族の支援体制の整備が急務である.

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：日本消化器病学会-甲信越支部  

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Language：Japanese   Publisher：(株)医学書院  

＜文献概要＞ポイント ◆内科,外科が緊密な連携をとり,ステロイド・免疫調節薬・生物学的製剤などの薬剤管理を行う.◆炎症性腸疾患に特徴的な,日和見感染,血栓症などの合併症も考慮に入れた適切な周術期管理が重要である.◆分割手術,ストーマ管理,合併症について,適切な対応と十分なインフォームド・コンセントが必要である.

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：日本臨床外科学会  

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Language：Japanese   Publisher：日本臨床外科学会  

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Language：English   Publisher：(一社)日本癌治療学会  

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Language：Japanese   Publisher：日本臨床外科学会  

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Recent progress in genomic analysis using next-generation sequencing technology has enabled the comprehensive detection of mutations and tumor mutation burden (TMB) in patients. A high TMB (TMB-H) tumor is defined as one with high somatic mutational rates, which correlates with clinical responses to certain treatments such as immunotherapies. We determined TMB in lung adenocarcinoma and clarified the characteristics of patients with TMB-H in relation to common driver mutations and smoking history. MATERIALS AND METHODS: Genomic aberrations and TMB were determined in Japanese patients with lung adenocarcinoma (n = 100) using next-generation sequencing of 415 known cancer genes. TMB-H was defined as > 20 mutations per megabase (Mb) of sequenced DNA. RESULTS: The median TMB was 13.5 (5-33) mutations/Mb. Ten of 100 (10%) patients showed TMB-H, and the others showed low TMB (TMB-L). Only two of 10 (20%) patients with TMB-H had one of the common driver mutations (ALK and ERBB2 mutation), whereas 57 of 90 (63%) patients with TMB-L had one of the driver mutations, including ALK, EGFR, ERBB2, ROS, RET, and MET (P < 0.05). Notably, no EGFR mutation was observed in patients with TMB-H. Eight of 10 (80%) patients with TMB-H had recent smoking history, whereas only 17 of 90 (19%) patients with TMB-L had recent smoking history (P < 0.001). CONCLUSIONS: We found that TMB-H is associated with smoking history, whereas TMB-L is associated with the common driver mutations in lung adenocarcinoma, which may impact treatment strategies for these patients.

DOI： 10.1016/j.jss.2018.07.007

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Language：Japanese   Publisher：日本臨床外科学会  

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Language：Japanese   Publisher：日本臨床外科学会  

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Language：Japanese   Publisher：日本臨床外科学会  

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Language：Japanese   Publisher：日本臨床外科学会  

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Language：English   Publishing type：Research paper (scientific journal)  

Next generation sequencing (NGS) has been an invaluable tool to put genomic sequencing into clinical practice. The incorporation of clinically relevant target sequences into NGS-based gene panel tests has generated practical diagnostic tools that enable individualized cancer-patient care. The clinical utility of gene panel testing includes investigation of the genetic basis for an individual's response to therapy, such as signaling pathways associated with a response to specific therapies, microsatellite instability and a hypermutated phenotype, and deficiency in the DNA double-strand break repair pathway. In this review, we describe the concept of precision cancer medicine using target sequences in gene panel tests as well as the importance of the control of sample quality in routine NGS-based genomic testing. We describe geographic and ethnic differences in cancer genomes, and discuss issues that need to be addressed in the future based on our experiences in Japan.

DOI： 10.1111/cas.13837

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Language：Japanese   Publisher：新潟医学会  

【目的】近年、加齢に伴う様々な機能低下、いわゆる「フレイル」が注目されている。要介護の主な原因となる運動器障害、脳血管障害、認知症などの領域ではフレイルの研究が進んでいるが、消化器外科領域では報告が少ない。本研究では、消化器外科患者における術前フレイルの現状を把握し、フレイルの状態が術後成績に与える影響を明らかにすることを目的とした。【対象と方法】2017年10月〜2018年1月に、手術を目的として新潟大学医歯学総合病院消化器外科外来を受診した消化器外科疾患患者61名を対象とした。外来受診時に日本版Cardiovascular Health Study基準によるフレイル評価を行った。また、手術症例において、術後合併症の有無、入院期間、術後転帰について健常群/プレフレイル群/フレイル群に分けて比較検討した。【結果】対象61名の内訳は、男性40名、女性21名、年齢の中央値は67歳(範囲:18-89歳)であった。51名(83.6%)では手術が施行されたが、10名(16.4%)は、切除不能(6名)、耐術不能(4名)の理由により手術適応なしと判断された。手術適応なしの症例では、健常群は認めず、フレイル群は3名(30.0%)認められた。手術施行症例では健常群は12名(23.5%)認められ、フレイル群は7名(13.7%)であった。術後合併症は健常群では1名(8.3%)、プレフレイル群では9名(28.1%)、フレイル群では4名(57.1%)で認められた(P=0.07)。手術症例における入院期間の検討では、フレイルの進行によって入院期間が有意に延長していた(P=0.008)。転帰としては、自宅退院が50名(98.0%)、転院が1名(2.0%)、死亡退院は認めなかった。【結論】消化器外科領域における術前フレイル評価は、手術適応判断、周術期管理において有用である可能性が示唆された。(著者抄録)

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Language：English   Publisher：(一社)日本癌学会  

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Lymphatic metastasis is known to contribute to worse prognosis of biliary tract cancer (BTC). Recently, sphingosine-1-phosphate (S1P), a bioactive lipid mediator generated by sphingosine kinase 1 (SPHK1), has been shown to play an important role in lymphangiogenesis and lymph node metastasis in several types of cancer. However, the role of the lipid mediator in BTC has never been examined. Here we found that S1P is elevated in BTC with the activation of ceramide-synthetic pathways, suggesting that BTC utilizes SPHK1 to promote lymphatic metastasis. We found that S1P, sphingosine and ceramide precursors such as monohexosyl-ceramide and sphingomyelin, but not ceramide, were significantly increased in BTC compared to normal biliary tract tissue using LC-ESI-MS/MS. Utilizing The Cancer Genome Atlas cohort, we demonstrated that S1P in BTC is generated via de novo pathway and exported via ABCC1. Further, we found that SPHK1 expression positively correlated with factors related to lymphatic metastasis in BTC. Finally, immunohistochemical examination revealed that gallbladder cancer with lymph node metastasis had significantly higher expression of phospho-SPHK1 than that without. Taken together, our data suggest that S1P generated in BTC contributes to lymphatic metastasis.

DOI： 10.1038/s41598-018-29144-9

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn's disease (CD), is a chronic, idiopathic, repeated inflammatory disease. Colorectal cancer (CRC) that develops in patients with IBD is known as colitis-associated colorectal cancer (CAC), but the underlying carcinogenic mechanism remains unclear. Genomic analysis of sporadic CRC has been well described based on next-generation sequencing (NGS) data. Using NGS, we compared all exons of 415 cancer-associated genes in patients in Japan and the USA who had CRC and found similar genomic alteration patterns among the two populations. However, genomic analysis of CAC has not been thoroughly investigated. MAIN BODY: The molecular pathogenesis of CAC shares many features with sporadic CRC, but there are distinct variations in the time and frequency of some alterations. Gene alterations in CAC are gradually being elucidated using genomic sequencing analyses. Some studies have shown that gene alteration patterns differ between UC and CD. The carcinogenesis of CAC depends on unique environmental, genetic, and immunological factors. CONCLUSIONS: In this review, we have discussed the differences in genomic alterations between sporadic CRC and CAC. NGS in patients with IBD has the potential to detect early CAC and to suggest therapeutic targets.

DOI： 10.1186/s12957-018-1428-0

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Lung squamous cell carcinoma (LSCC) is a major histological subtype of lung cancer. In this study, we investigated genomic alterations in LSCC and evaluated the clinical implications of mutation burden (MB) in LSCC. METHODS: Genomic alterations were determined in Japanese patients with LSCC (N = 67) using next-generation sequencing of 415 known cancer genes. MB was defined as the number of non-synonymous mutations per 1 Mbp. Programmed death-ligand 1 (PD-L1) protein expression in cancer cells was evaluated by immunohistochemical analysis. RESULTS: TP53 gene mutations were the most common alteration (n = 51/67, 76.1%), followed by gene alterations in cyclin-dependent kinase inhibitor 2B (CDKN2B; 35.8%), CDKN2A (31.3%), phosphatase and tensin homolog (30.0%), and sex-determining region Y-box 2 (SOX2, 28.3%). Histological differentiation was significantly poorer in tumors with high MB (greater than or equal to the median MB) compared with that in tumors with low MB (less than the median MB; p = 0.0446). The high MB group had more tumors located in the upper or middle lobe than tumors located in the lower lobe (p = 0.0019). Moreover, cancers in the upper or middle lobes had significantly higher MB than cancers in the lower lobes (p = 0.0005), and tended to show higher PD-L1 protein expression (p = 0.0573). SOX2 and tyrosine kinase non-receptor 2 amplifications were associated with high MB (p = 0.0065 and p = 0.0010, respectively). CONCLUSIONS: The MB level differed according to the tumor location in LSCC, suggesting that the location of cancer development may influence the genomic background of the tumor.

DOI： 10.1245/s10434-018-6401-1

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This study aimed to compare common histologic markers at the invasive front of colon adenocarcinoma in terms of prognostic accuracy and interobserver agreement. Consecutive patients who underwent curative resection for stages I to III colon adenocarcinoma at a single institution in 2007 to 2014 were identified. Poorly differentiated clusters (PDCs), tumor budding, perineural invasion, desmoplastic reaction, and Crohn-like lymphoid reaction at the invasive front, as well as the World Health Organization (WHO) grade of the entire tumor, were analyzed. Prognostic accuracies for recurrence-free survival (RFS) were compared, and interobserver agreement among 3 pathologists was assessed. The study cohort consisted of 851 patients. Although all the histologic markers except WHO grade were significantly associated with RFS (PDCs, tumor budding, perineural invasion, and desmoplastic reaction: P<0.001; Crohn-like lymphoid reaction: P=0.021), PDCs (grade 1 [G1]: n=581; G2: n=145; G3: n=125) showed the largest separation of 3-year RFS in the full cohort (G1: 94.1%; G3: 63.7%; hazard ratio [HR], 6.39; 95% confidence interval [CI], 4.11-9.95; P<0.001), stage II patients (G1: 94.0%; G3: 67.3%; HR, 4.15; 95% CI, 1.96-8.82; P<0.001), and stage III patients (G1: 89.0%; G3: 59.4%; HR, 4.50; 95% CI, 2.41-8.41; P<0.001). PDCs had the highest prognostic accuracy for RFS with the concordance probability estimate of 0.642, whereas WHO grade had the lowest. Interobserver agreement was the highest for PDCs, with a weighted kappa of 0.824. The risk of recurrence over time peaked earlier for worse PDCs grade. Our findings indicate that PDCs are the best invasive-front histologic marker in terms of prognostic accuracy and interobserver agreement. PDCs may replace WHO grade as a prognostic indicator.

DOI： 10.1097/PAS.0000000000001059

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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PURPOSE: Small bowel obstruction (SBO) remains a common complication after pelvic or abdominal surgery. However, the risk factors for SBO in ulcerative colitis (UC) surgery are not well known. The aim of the present study was to clarify the risk factors associated with SBO after ileal pouch-anal anastomosis (IPAA) with a loop ileostomy for patients with UC. METHODS: The medical records of 96 patients who underwent IPAA for UC between 1999 and 2011 were reviewed. SBO was confirmed based on the presence of clinical symptoms and radiographic findings. The patients were divided into 2 groups: the SBO group and the non-SBO group. We also analyzed the relationship between SBO and computed tomography (CT) scan image parameters. RESULTS: The study included 49 male and 47 female patients. The median age was 35.5 years (range, 14-72 years). We performed a 2- or 3-stage procedure as a total proctocolectomy and IPAA for patients with UC. SBO in the pretakedown of the loop ileostomy after IPAA occurred in 22 patients (22.9%). Moreover, surgical intervention for SBO was required for 11 patients. In brief, closure of the loop ileostomy was performed earlier than expected. A multivariate logistic regression analysis revealed that the 2-stage procedure (odds ratio, 2.850; 95% confidence interval, 1.009-8.044; P = 0.048) was a significant independent risk factor associated with SBO. CT scan image parameters were not significant risk factors of SBO. CONCLUSION: The present study suggests that a 2-stage procedure is a significant risk factor associated with SBO after IPAA in patients with UC.

DOI： 10.3393/ac.2017.06.14

PubMed

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：English   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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IMPORTANCE: Guidelines recommend measuring preoperative carcinoembryonic antigen (CEA) in patients with colon cancer. Although persistently elevated CEA after surgery has been associated with increased risk for metastatic disease, prognostic significance of elevated preoperative CEA that normalized after resection is unknown. OBJECTIVE: To investigate whether patients with elevated preoperative CEA that normalizes after colon cancer resection have a higher risk of recurrence than patients with normal preoperative CEA. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort analysis was conducted at a comprehensive cancer center. Consecutive patients with colon cancer who underwent curative resection for stage I to III colon adenocarcinoma at the center from January 2007 to December 2014 were identified. EXPOSURES: Patients were grouped into 3 cohorts: normal preoperative CEA, elevated preoperative but normalized postoperative CEA, and elevated preoperative and postoperative CEA. MAIN OUTCOMES AND MEASURES: Three-year recurrence-free survival (RFS) and hazard function curves over time were analyzed. RESULTS: A total of 1027 patients (461 [50.4%] male; median [IQR] age, 64 [53-75] years) were identified. Patients with normal preoperative CEA had 7.4% higher 3-year RFS (n = 715 [89.7%]) than the combined cohorts with elevated preoperative CEA (n = 312 [82.3%]) (P = .01) but had RFS similar to that of patients with normalized postoperative CEA (n = 142 [87.9%]) (P = .86). Patients with elevated postoperative CEA had 14.9% lower RFS (n = 57 [74.5%]) than the combined cohorts with normal postoperative CEA (n = 857 [89.4%]) (P = .001). The hazard function of recurrence for elevated postoperative CEA peaked earlier than for the other cohorts. Multivariate analyses confirmed that elevated postoperative CEA (hazard ratio [HR], 2.0; 95% CI, 1.1-3.5), but not normalized postoperative CEA (HR, 0.77; 95% CI, 0.45-1.30), was independently associated with shorter RFS. CONCLUSIONS AND RELEVANCE: Elevated preoperative CEA that normalizes after resection is not an indicator of poor prognosis. Routine measurement of postoperative, rather than preoperative, CEA is warranted. Patients with elevated postoperative CEA are at increased risk for recurrence, especially within the first 12 months after surgery.

DOI： 10.1001/jamaoncol.2017.4420

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Language：Japanese   Publisher：(一社)日本胃癌学会  

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Language：Japanese   Publisher：(株)篠原出版新社  

Stage IV大腸癌109例を対象とし、次世代シークエンサーを用いた癌遺伝子変異解析パネル(415遺伝子)で遺伝子変異を解析した。RAS変異群26例(23.9%)、RAS変異+PTEN欠失群16例(14.7%)、PTEN欠失+ERBB2増幅群16例(14.7%)、PTEN欠失+SRC増幅/欠失群8例(7.3%)、A11野生型群27例(24.8%)、BRAF変異+RNF43変異群9例(7.3%)、その他8例(7.3%)にカテゴリー分類された。実際に抗EGFR抗体薬を使用した40例の検討では、A11野生型群は、RASKETで判定できるKRAS/NRAS遺伝子以外の遺伝子に変異のある群に比べて、無増悪生存率(PFS)が有意に良好であった。

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Language：English   Publisher：(一社)日本胃癌学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AME Publishing Company  

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm of the gastrointestinal tract. However, rectal GIST is rare, the incident rate of it is approximately 5% of all GISTs. Rectal GIST symptoms generally include bleeding and/or pain and occasionally, urinary symptoms. Immunohistochemical evaluation finds that most rectal GIST tumors are CD117 (KIT) positive, and are sometimes CD34, platelet-derived growth factor receptor alpha (PDGFRA), smooth muscle actin, S-100, or vimentin positive. The National Institutes of Health (NIH) classifies rectal GIST as very-low risk, low risk, intermediate risk, or high risk, and the frequencies have been estimated as 0-23.8% for very-low risk, 0-45% for low risk, 0-34% for intermediate risk, and 21-100% for high risk tumors. The first-line treatment for localized GIST is curative resection, but is difficult in rectal GIST because of anatomical characteristics such as the deep, narrow pelvis and proximity to the sphincter muscle or other organs. Several studies noted the efficacy of the minimally invasive surgery, such as trans-anal, trans-sacral, trans-vaginal resection, or laparoscopic resection. The appropriate surgical procedure should be selected depending on the case. Imatinib mesylate (IM) is indicated as first-line treatment of metastatic or unresectable GIST, and clinical outcomes are correlated with KIT mutation genotype. However, the KIT mutation genotypes in rectal GIST are not well known. In this review, as in other GISTs, a large proportion (59-100%) of rectal GISTs carry exon 11 mutations. Although curative resection is indicated for localized rectal GIST, a high rate of local recurrence is a problem. Multimodal therapy including perioperative IM may improve postoperative outcomes, contributing to anus-preserving surgery. Moreover, KIT mutation analysis before IM treatment is important. This review summarizes current treatment strategies for rectal GIST.

DOI： 10.21037/tgh.2018.01.08

Scopus

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Next-generation sequencing (NGS) has enabled comprehensive detection of genomic alterations in lung cancer. Ethnic differences may play a critical role in the efficacy of targeted therapies. The aim of this study was to identify and compare genomic alterations of lung adenocarcinoma between Japanese patients and the Cancer Genome Atlas (TCGA), which majority of patients are from the US. We also aimed to examine prognostic impact of additional genomic alterations in patients harboring EGFR mutations. Genomic alterations were determined in Japanese patients with lung adenocarcinoma (N = 100) using NGS-based sequencing of 415 known cancer genes, and correlated with clinical outcome. EGFR active mutations, i.e., those involving exon 19 deletion or an L858R point mutation, were seen in 43% of patients. Some differences in driver gene mutation prevalence were observed between the Japanese cohort described in the present study and the TCGA. Japanese cohort had significantly more genomic alterations in cell cycle pathway, i.e., CDKN2B and RB1 than TCGA. Concurrent mutations, in genes such as CDKN2B or RB1, were associated with worse clinical outcome in patients with EGFR active mutations. Our data support the utility of comprehensive sequencing to detect concurrent genomic variations that may affect clinical outcomes in this disease.

DOI： 10.1038/s41598-017-18560-y

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Language：Japanese   Publisher：(株)医学書院  

＜ポイント＞閉塞性大腸炎をきたす疾患として大腸癌が最も多いが,憩室炎,虚血性腸疾患,便秘なども原因となりうる.閉塞部から離れた口側腸管にびらん・潰瘍を認めることが多く,切除範囲の設定には注意を要する.ステント治療により,口側腸管の評価や減圧が可能となり,閉塞性大腸炎のマネジメントに変化がみられる.(著者抄録)

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PURPOSE: It has been suggested that the biological characteristics of breast cancer may differ among different geographic or ethnic populations. Indeed, triple-negative breast cancer (TNBC), the most lethal breast cancer subgroup, has been reported to show a higher incidence in Japan than in the US. However, most genomic studies of these tumors are from Western countries and the genomic landscape of TNBC in an Asian population has not been thoroughly investigated. Here, we sought to elucidate the geographic and ethnic diversity of breast cancer by examining actionable driver alterations in TNBC tumors from Japanese patients and comparing them with The Cancer Genome Atlas (TCGA) database, which gather data primarily from non-Asian patients. MATERIALS AND METHODS: We performed comprehensive genomic profiling, including an analysis of 435 known cancer genes on Japanese TNBC patients (N=53) and compared the results to independent data obtained from TCGA (N=123). RESULTS: Driver alterations were identified in 51 out of 53 Japanese patients (96%). Although the overall alteration spectrum of Japanese patients was similar to that of the TCGA, we found significant differences in the frequencies of alterations in MYC and PTK2. We identified three patients (5.7%) with a high tumor mutation burden, although no microsatellite instability was observed in any of the Japanese patients. Importantly, pathway analysis revealed that 66.0% (35/53) of Japanese patients, as well as 66.7% (82/123) of the TCGA cohort, had alterations in at least one actionable gene targetable by an FDA-approved drug. CONCLUSION: Our study identified actionable driver alterations in Japanese patients with TNBC, revealing new opportunities for targeted therapies in Asian patients.

DOI： 10.1200/po.17.00211

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DOI： 10.1200/PO.18.00097

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INTRODUCTION: Precision medicine is only possible in oncology practice if targetable genes in fragmented DNA, such as DNA from formalin-fixed paraffin-embedded (FFPE) samples, can be sequenced using next generation sequencing (NGS). The aim of this study was to examine the quality and quantity of DNA from FFPE cancerous tissue samples from surgically resected and biopsy specimens. METHODS: DNA was extracted from unstained FFPE tissue sections prepared from surgically resected specimens of breast, colorectal and gastric cancer, and biopsy specimens of breast cancer. A total quantity of DNA ≥60 ng from a sample was considered adequate for NGS. The DNA quality was assessed by Q-ratios, with a Q-ratio >0.1 considered sufficient for NGS. RESULTS: The Q-ratio for DNA from FFPE tissue processed with neutral-buffered formalin was significantly better than that processed with unbuffered formalin. All Q-ratios for DNA from breast, colorectal and gastric cancer samples indicated DNA levels sufficient for NGS. DNA extracted from gastric cancer FFPE samples prepared within the last 7 years is suitable for NGS analysis, whereas those older than 7 years may not be suitable. Our data suggested that adequate amounts of DNA can be extracted from FFPE samples, not only of surgically resected tissue but also of biopsy specimens. CONCLUSIONS: The type of formalin used for fixation and the time since FFPE sample preparation affect DNA quality. Sufficient amounts of DNA can be extracted from FFPE samples of both surgically resected and biopsy tissue, thus expanding the potential diagnostic uses of NGS in a clinical setting.

DOI： 10.1016/j.jss.2017.06.077

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Language：Japanese   Publisher：(株)癌と化学療法社  

症例は81歳、女性。C型肝硬変で通院中にCTで肝S7に径20mm大の腫瘤を指摘され、肝細胞癌(HCC)と診断された。高齢であり本人が肝切除を望まなかったので、病変に対して2回の肝動脈化学塞栓療法(TACE)を施行した。1年後のCTで局所再発と大動脈周囲リンパ節転移を認めた。局所再発に対してはTACEを施行し、大動脈周囲リンパ節転移に対しては外科切除を施行した。外科切除から6ヵ月後、CTで縦隔リンパ節転移を認め、放射線局所照射療法を施行した。原病の診断から7年が経過した現在、無再発で外来経過観察中である。HCCの肝外転移再発は肺、骨、リンパ節への転移が多く、有効な治療法は確立されていない。孤立性のリンパ節転移を伴うHCCに対して、TACE、外科切除、放射線局所照射療法を組み合わせた集学的治療は予後延長に寄与する可能性がある。(著者抄録)

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：IMPACT JOURNALS LLC  

Objectives: Anti-epidermal growth factor receptor (EGFR) therapy has been found to be more effective against left-sided colorectal cancer (LCRC) than right-sided colorectal cancer (RCRC). We hypothesized that RCRC is more likely to harbor genetic alterations associated with resistance to anti-EGFR therapy and tested this using comprehensive genomic sequencing.
Materials and methods: A total of 201 patients with either primary RCRC or LCRC were analyzed. We investigated tumors for genetic alterations using a 415-gene panel, which included alterations associated with resistance to anti-EGFR therapy: TK receptors (ERBB2, MET, EGFR, FGFR1, and PDGFRA), RAS pathway (KRAS, NRAS, HRAS, BRAF, and MAPK2K1), and PI3K pathway (PTEN and PIK3CA). Patients whose tumors had no alterations in these 12 genes, theoretically considered to respond to anti-EGFR therapy, were defined as "all wild-type", while remaining patients were defined as "mutant-type".
Results: Fifty-six patients (28%) and 145 patients (72%) had RCRC and LCRC, respectively. Regarding genetic alterations associated with anti-EGFR therapy, only 6 of 56 patients (11%) with RCRC were "all wild-type" compared with 41 of 145 patients (28%) with LCRC (P = 0.009). Among the 49 patients who received anti-EGFR therapy, RCRC showed significantly worse progression-free survival (PFS) than LCRC (P = 0.022), and "mutant-type" RCRC showed significantly worse PFS compared with "all wild-type" LCRC (P = 0.004).
Conclusions: RCRC is more likely to harbor genetic alterations associated with resistance to anti-EGFR therapy compared with LCRC. Furthermore, our data shows primary tumor sidedness is a surrogate for the non-random distribution of genetic alterations in CRC.

DOI： 10.18632/oncotarget.20510

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A 71-year-old man presented with sudden abdominal pain. He had past history of atrial fibrillation, cerebral infarction and heart-valve replacement and received anticoagulant therapy with warfarin. Computed tomography of the abdomen revealed bloody ascites and a huge mass in contact with the third portion of the duodenum. The mass was encapsulated and consisted of a solid component with calcification and hematoma. Under the preoperative diagnosis of gastrointestinal stromal tumor with intra-abdominal bleeding, laparotomy was performed. Intraoperative findings revealed the tumor arising from the right mesocolon and excision of the tumor with right hemicolectomy was performed. Histologic examination confirmed a diagnosis of mixed type liposarcoma. No postoperative complication was observed and he was discharged home on the 8th postoperative day. He remains alive and well with no evidence of disease 52 months after resection.

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Carcinoma with elevated SRC expression is associated with distant metastasis and drug resistance. We report 2 cases of SRC amplification observed after retrospective comprehensive genomic sequencing. Case 1 was a 62-year-old man who had RAS wild-type stage IV carcinoma of the sigmoid colon with multiple liver metastases in both lobes. He underwent low anterior resection and systemic chemotherapy was initiated to treat the unresectable multiple liver metastases. Case 2 was a 73-yearold man who had RAS wild-type stage IV carcinoma of the descending colon with metastasis in the lateral segment of the liver. He underwent left hemicolectomy and lateral segmentectomy. He subsequently underwent open radiofrequency ablation and systemic chemotherapy to treat a hepatic recurrence. Several previous studies have found that molecular targeted therapy with tyrosine kinase inhibitors is effective against colorectal cancer with elevated SRC expression. This suggests that the results of comprehensive genomic sequencing may support the implementation of new treatments.

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症例は71歳、男性。急激な腹痛を主訴に当科を受診した。心房細動、脳梗塞、心弁置換術後の既往を有し、ワーファリンを内服中であった。腹部造影CTで血性腹水と十二指腸水平脚に接する巨大な腫瘤を認めた。腫瘤は石灰化を伴う充実性部分と新旧の血腫とが混在して被包化されていた。十二指腸原発の消化管間質腫瘍の穿破による腹腔内出血が疑われ、開腹手術が施行された。術中所見で右側結腸間膜原発の脂肪肉腫が疑われ、結腸右半切除術を伴う腫瘤摘出術が施行された。病理組織学的にて腫瘍内出血を伴う混合型脂肪肉腫と診断された。術後は合併症なく経過し、術後第8病日目に退院した。術後52ヵ月が経過した現在、無再発生存中である。非常にまれではあるが、特に抗凝固療法中においては脂肪肉腫が腹腔内出血の一因となることもある。(著者抄録)

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The patient was a 73-year-old man with ascending colon cancer and synchronous liver metastases. A right hemicolectomy with a lymph node dissection was performed for the primary lesion. The resected specimen revealed a KRAS codon 12 mutation. After 6 courses of chemotherapy with capecitabine, oxaliplatin, and bevacizumab(Bv), we performed a partial hepatectomy and resection of the peritoneal dissemination. A computed tomography(CT)scan 5 months later revealed the recurrence of the liver metastases. After 8 courses of chemotherapy with 5-fluorouracil, Leucovorin, irinotecan, and Bv, we performed a partial hepatectomy. CT scan after 13 months revealed a recurrence in the peritoneal dissemination in the Douglas pouch and the right subphrenic space; therefore, we performed a low anterior resection and resection of the peritoneal dissemination with curative intent. CT scan after 19 months revealed a recurrence in the right subphrenic dissemination, a lung metastasis, and pleural dissemination. Chemotherapy with 5-fluorouracil, Leucovorin, and Bv was administered for 2 years and 5 months. After 5 years and 9 months of the primary operation, the patient is alive. Recently, we have focused on the mechanism of multidrug resistance through NAD(P)H: quinone oxidoreductase-1(NQO1)overexpression, which can be used to determine the role of an enzyme in sensitivity to toxicity and carcinogenesis. In this case, the pathological examination of the resected specimen revealed NQO1 negative expression. In conclusion, NQO1 may play a significant role in chemotherapy resistance in colorectal cancer patients.

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SRC発現の亢進した癌は遠隔転移や薬剤耐性と関連があり、治療抵抗性とされている。今回、次世代シークエンサーによる415の癌関連遺伝子パネルを使用した後方視的な解析により、SRC増幅を認めた2例を報告する。症例1は62歳、男性。両葉多発肝転移を伴うRAS野生型cStage IVのS状結腸癌に対して、S状結腸切除を施行した。切除不能多発肝転移に対して、化学療法を行った。症例2は73歳、男性。肝外側区域に転移を伴うRAS野生型cStage IVの下行結腸癌に対して、左半結腸切除および外側区域切除を施行した。その後、肝再発に対して開腹ラジオ波焼灼術および化学療法を行った。SRC発現の亢進した大腸癌に対して、チロシンキナーゼ阻害薬による分子標的治療が有効であるという報告がある。包括的癌ゲノム検査により、新たな治療提案ができる可能性が示唆された。(著者抄録)

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症例は73歳、男性。下腹部痛を主訴に受診し、精査で上行結腸癌、多発肝転移と診断され、結腸右半切除を施行した。術後のKRAS遺伝子検査ではcodon 12の変異を認めた。CapeOX+bevacizumab(Bv)療法後に肝部分切除を施行したが、5ヵ月後に新規肝転移病変を認めた。FOLFIRI+Bv療法後に再度肝部分切除を施行し、8ヵ月後にダグラス窩と右横隔膜下の腹膜播種を認めたため、同病変に対して低位前方切除、腹膜播種切除を施行した。6ヵ月後に右横隔膜下の腹膜播種、肺転移、胸膜播種を認め、sLV5FU2(+Bv)療法を継続している。初回手術から5年9ヵ月、全身状態良好で通院中である。近年、抗酸化ストレス蛋白の一つであるNAD(P)H:quinone oxidoreductase-1(NQO1)の抗癌剤耐性に関する報告が散見される。本症例の原発巣切除標本の免疫組織化学染色ではNQO1発現が陰性であり、病勢制御や長期生存に関与している可能性が考えられる。(著者抄録)

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Language：Japanese   Publishing type：Research paper (scientific journal)  

This study aimed to evaluate the health-related quality of life(QOL)using EQ-5D-5L scores for patients who underwent surgery for colorectal cancer. A total of 30 consecutive patients(14 men and 16 women; median age: 67.5 years)from the outpatient clinic of our institute in January 2017 were eligible for this study. The primary tumor was located in the colon(n= 18)or rectum/anu(s n=12). Twelve patient(s 40.0%)had cancer recurrence, and 3 patient(s 10.0%)had a stoma. In addition, 11 patients(36.7%)underwent chemotherapy. The median EQ-5D-5L score for all the patients was 0.867(range, 0.324- 1.000). The EQ-5D-5L score of patients with recurrence was significantly lower(0.820)than that of patients without recurrence( 0.948)(p=0.002). Furthermore, the EQ-5D-5L score of women(0.834)was significantly lower than that of men (0.942)(p=0.015). No significant difference was noted between the EQ-5D-5L score and other factors, such as age, cancer stage, location of primary tumor, absence/presence of chemotherapy, and absence/presence of stoma. In conclusion, using EQ-5D-5L scores, female gender and cancer recurrence were found to be associated with low QOL of patients after surgery for colorectal cancer.

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Language：Japanese   Publishing type：Research paper (scientific journal)  

Lymph node metastasis has a poor prognosis in patients with hepatocellular carcinoma(HCC). We report a case of HCC with lymph node metastasis successfully treated by multidisciplinary treatment. An 81-year-old woman who was followed up for liver cirrhosis received a diagnosis of HCC, which was detected by CT as a solitary tumor 20mm in diameter in the couinaud segment 7 of the liver. She underwent transcatheter arterial chemoembolization(TACE)twice for HCC because of her advanced age and no intention to undergo hepatectomy. Some 12 months later, local recurrence was managed by repeat TACE and paraaortic lymph node metastasis by surgical resection. The patient received radiotherapy for mediastinal nodal disease 6 months after the resection. She remains alive and well without no evidence of disease 84 months after the initial treatment. This case and a review of the literature suggest that multidisciplinary treatment with TACE, surgical resection and radiotherapy may provide a survival benefit for selected patients with HCC with isolated lymph node metastasis.

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Language：Japanese   Publisher：日本臨床外科学会  

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Language：Japanese   Publisher：日本臨床外科学会  

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: A prospective randomized study was performed to investigate the validity of intravenous carnitine administration during postoperative parenteral nutrition (PN) with lipid emulsion. METHODS: Patients undergoing surgery for gastric or colorectal cancer were enrolled in the study and were randomly divided into two groups (n = 8 in each group): 1) group L, who received a peripheral PN (PPN) solution of 7.5% glucose, 30% amino acid, and 20% lipid emulsion; and 2) group LC, who received the same PPN solution, as well as carnitine intravenously. PPN was performed from postoperative day (POD) 1 to POD4. Clinical and laboratory parameters were compared between the two groups; statistical significance was set at P < 0.05. RESULTS: Serum carnitine concentrations were significantly higher in group LC on POD3 (P < 0.01) and POD7 (P = 0.01). Postoperative changes in laboratory parameters and morbidity were comparable between the two groups. However, the decrease in C-reactive protein from POD3 to POD7 was significantly greater in group LC than in group L (P = 0.011). CONCLUSION: The results show that intravenous carnitine administration in addition to PN is safe and may be beneficial for recovery from postoperative inflammatory reactions.

DOI： 10.14740/jocmr3113w

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Language：English   Publishing type：Research paper (scientific journal)  

AIM: To assess the clinical significance of prophylactic lateral pelvic lymph node dissection (LPLND) in stage IV low rectal cancer. METHODS: We selected 71 consecutive stage IV low rectal cancer patients who underwent primary tumor resection, and enrolled 50 of these 71 patients without clinical LPLN metastasis. The patients had distant metastasis such as liver, lung, peritoneum, and paraaortic LN. Clinical LPLN metastasis was defined as LN with a maximum diameter of 10 mm or more on preoperative pelvic computed tomography scan. All patients underwent primary tumor resection, 27 patients underwent total mesorectal excision (TME) with LPLND (LPLND group), and 23 patients underwent only TME (TME group). Bilateral LPLND was performed simultaneously with primary tumor resection in LPLND group. R0 resection of both primary and metastatic sites was achieved in 20 of 50 patients. We evaluated possible prognostic factors for 5-year overall survival (OS), and compared 5-year cumulative local recurrence between the LPLND and TME groups. RESULTS: For OS, univariate analyses revealed no significant benefit in the LPLND compared with the TME group (28.7% vs 17.0%, P = 0.523); multivariate analysis revealed that R0 resection was an independent prognostic factor. Regarding cumulative local recurrence, the LPLND group showed no significant benefit compared with TME group (21.4% vs 14.8%, P = 0.833). CONCLUSION: Prophylactic LPLND shows no oncological benefits in patients with Stage IV low rectal cancer without clinical LPLN metastasis.

DOI： 10.5306/wjco.v8.i5.412

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Language：Japanese   Publisher：日本臨床外科学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BIOMED CENTRAL LTD  

Background: Intertumoral heterogeneity represents a significant hurdle to identifying optimized targeted therapies in gastric cancer (GC). To realize precision medicine for GC patients, an actionable gene alteration-based molecular classification that directly associates GCs with targeted therapies is needed.& para;& para;Methods: A total of 207 Japanese patients with GC were included in this study. Formalin-fixed, paraffin-embedded (FFPE) tum or tissues were obtained from surgical or biopsy specimens and were subjected, to DMA extraction. We generated comprehensive genomic profiling data using a 435-gene panel including 69 actionable genes paired, with US Food and Drug Administration-approved targeted therapies, and the evaluation o f Epstein-Barr virus (EBV) infection and microsatellite instability (MSI) status.& para;& para;Results: Comprehensive genomic sequencing detected at least one alteration o f 435 cancer-related genes in 194 GCs (93.7%) and o f 69 actionable genes in 141 GCs (68.1%). We classified the 207 GCs into four The Cancer Genome Atlas (TCGA) subtypes using the genomic profiling data; EBV (N = 9), MSI (N = 17), chromosomal instability (N = 119), and genomicaliy stable subtype (N = 62). Actionable gene alterations were not specific and were widely observed throughout all TCGA subtypes. To discover a novel classification which more precisely selects candidates for targeted therapies, 207 GCs were classified using hypermutated. phenotype and the mutation profile of 69 actionable genes. We identified a hypermutated group (N = 32), while the others (N = 175) were sub-divided into six dusters including five with actionable gene alterations: ERBB2 (N = 25), CDKN2A, and CDKN2B (N = 10), KRAS (N = 10), BRCA2 (N = 9), and ATM duster (N = 12). The clinical utility of this classification was demonstrated by a case of unresectable GC. with a remarkable response to anti-HER2 therapy in the ERBB2 duster.& para;& para;Conclusions: This actionable gene-based classification creates a framework for further studies for realizing precision medicine in GC.

DOI： 10.1186/s13073-017-0484-3

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Language：English   Publisher：(一社)日本癌学会  

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Language：English   Publisher：(一社)日本癌学会  

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Language：Japanese   Publisher：(一社)日本大腸肛門病学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：W B SAUNDERS CO-ELSEVIER INC  

HER2-targeted therapy is considered effective for KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer (CRC). In general, HER2 status is determined by the use of immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Comprehensive genomic sequencing (CGS) enables the detection of gene mutations and copy number alterations including KRAS mutation and HER2 amplification; however, little is known about the utility of CGS for detecting HER2-positive CRC. To assess its utility, we retrospectively investigated 201 patients with stage I-IV CRC. The HER2 status of the primary site was assessed using IHC and FISH, and HER2 amplification of the primary site was also assessed using CGS, and the findings of these approaches were compared in each patient. CGS successfully detected alterations in 415 genes including KRAS codon 12/13 mutation and HER2 amplification. Fifty-nine (29%) patients had a KRAS codon 12/13 mutation. Ten (5%) patients were diagnosed as HER2 positive because of HER2 MC 3+, and the same 10 (5%) patients had HER2 amplification evaluated using CGS. The results of HER2 status and HER2 amplification were completely identical in all 201 patients (P &lt; .001). Nine of the 10 HER2-positive patients were KRAS 12/13 wild-type and were considered possible candidates for HER2-targeted therapy. CGS has the same utility as IHC and FISH for detecting HER2-positive patients who are candidates for HER2-targeted therapy, and facilitates precision medicine and tailor-made treatment. (C) 2017 The Authors. Published by Elsevier Inc.

DOI： 10.1016/j.humpath.2017.02.004

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Language：Japanese   Publishing type：Research paper (scientific journal)  

A ciliated muconodular papillary tumor (CMPT) has been reported to be a low-grade malignant tumor or benign tumor, consisting of ciliated columnar cells and goblet cells with basaloid cell proliferation, occur in the peripheral lung. We present a case of CMPT in this report. A 42-year-old male was referred to our department due to a nodule detected in the peripheral left lower lobe of lung. The nodule was resected via wedge resection based on a suspected diagnosis of carcinoma. Intraoperative analysis of the frozen sections was suggestive of mucinous adenocarcinoma. A left lower lobectomy and mediastinal lymph node dissection were performed. The resected specimen was characterized as a papillary tumor with central fibrosis, proliferating along the alveolar walls, surrounded by mucous lakes, and consisting of ciliated columnar cells and goblet cells. Nuclear atypia was mild, and no mitotic activity was observed. Based on these findings, the tumor was finally diagnosed as CMPT. No recurrence has been noted for 24 months after surgery.

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Language：Japanese   Publisher：新潟医学会