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BACKGROUND: The clinico-oncological outcomes of precursor epithelial subtypes of adenocarcinoma arising from intraductal papillary mucinous neoplasms (A-IPMN) are limited to small cohort studies. Differences in recurrence patterns and response to adjuvant chemotherapy between A-IPMN subtypes are unknown. METHODS: Clincopathological features, recurrence patterns and long-term outcomes of patients undergoing pancreatic resection (2010-2020) for A-IPMN were reported from 18 academic pancreatic centres worldwide. Precursor epithelial subtype groups were compared using uni- and multivariate analysis. RESULTS: In total, 297 patients were included (median age, 70 years; male, 78.9%), including 54 (18.2%) gastric, 111 (37.3%) pancreatobiliary, 80 (26.9%) intestinal and 52 (17.5%) mixed subtypes. Gastric, pancreaticobiliary and mixed subtypes had comparable clinicopathological features, yet the outcomes were significantly less favourable than the intestinal subtype. The median time to recurrence in gastric, pancreatobiliary, intestinal and mixed subtypes were 32, 30, 61 and 33 months. Gastric and pancreatobiliary subtypes had worse overall recurrence (p = 0.048 and p = 0.049, respectively) compared with the intestinal subtype but gastric and pancreatobiliary subtypes had comparable outcomes. Adjuvant chemotherapy was associated with improved survival in the pancreatobiliary subtype (p = 0.049) but not gastric (p = 0.992), intestinal (p = 0.852) or mixed subtypes (p = 0.723). In multivariate survival analysis, adjuvant chemotherapy was associated with a lower likelihood of death in pancreatobiliary subtype, albeit with borderline significance [hazard ratio (HR) 0.56; 95% confidence interval (CI) 0.31-1.01; p = 0.058]. CONCLUSIONS: Gastric, pancreatobiliary and mixed subtypes have comparable recurrence and survival outcomes, which are inferior to the more indolent intestinal subtype. Pancreatobiliary subtype may respond to adjuvant chemotherapy and further research is warranted to determine the most appropriate adjuvant chemotherapy regimens for each subtype.

DOI： 10.1245/s10434-024-15677-z

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OBJECTIVE: This international multicenter cohort study aims to identify recurrence patterns and treatment of first and second recurrence in a large cohort of patients after pancreatic resection for adenocarcinoma arising from intraductal papillary mucinous neoplasm (IPMN). BACKGROUND: Recurrence patterns and treatment of recurrence postresection of adenocarcinoma arising from IPMN are poorly explored. METHODS: Patients undergoing pancreatic resection for adenocarcinoma from IPMN between January 2010 and December 2020 at 18 pancreatic centers were identified. Survival analysis was performed using the Kaplan-Meier log-rank test and multivariable logistic regression by Cox-Proportional Hazards modeling. End points were recurrence (time-to, location, and pattern of recurrence) and survival (overall survival and adjusted for treatment provided). RESULTS: Four hundred fifty-nine patients were included (median, 70 years; interquartile range, 64-76; male, 54%) with a median follow-up of 78.1 months. Recurrence occurred in 209 patients [45.5%; median time to recurrence, 12.8 months; early recurrence (within 1 years), 23.2%]. Eighty-three (18.1%) patients experienced a local regional recurrence, and 164 (35.7%) patients experienced a distant recurrence. Adjuvant chemotherapy was not associated with reduction in recurrence (hazard ratio 1.09; P =0.669) One hundred twenty patients with recurrence received further treatment. The median survival with and without additional treatment was 27.0 and 14.6 months ( P <0.001), with no significant difference between treatment modalities. There was no significant difference in survival between locations of recurrence ( P =0.401). CONCLUSIONS: Recurrence after pancreatic resection for adenocarcinoma arising from IPMN is frequent with a quarter of patients recurring within 12 months. Treatment of recurrence is associated with improved overall survival and should be considered.

DOI： 10.1097/SLA.0000000000006144

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

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DOI： 10.1245/s10434-024-15224-w

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DOI： 10.1245/s10434-024-15345-2

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BACKGROUND: Evaluation of human epidermal growth factor receptor 2 (HER2) overexpression caused by erb-b2 receptor tyrosine kinase 2 (ERBB2) amplification (AMP) by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) is essential for treating unresectable metastatic gastric cancer (GC). A targeted tumour sequencing test enables comprehensive assessment of alterations in cancer-related genes, including ERBB2. This study aimed to evaluate the concordance between the targeted tumour sequencing test and IHC/FISH for detecting HER2-positive GC and to clarify the significance of ERBB2 AMP and concomitant genetic alterations in HER2 downstream pathways (DPs) in anti-HER2 therapy for unresectable metastatic GC patients. METHODS: ERBB2 copy number alteration (CNA) was examined via a targeted tumour sequencing test in 152 formalin-fixed paraffin-embedded (FFPE) GC tissues. ERBB2 CNA was compared to HER2 status evaluated by IHC/FISH in FFPE block sections, which were identical to those subjected to the targeted tumour sequencing test. Treatment outcomes of anti-HER2 therapy in 11 patients with unresectable metastatic GC was evaluated. RESULTS: ERBB2 AMP (≥ 2.5-fold change) was detected by the targeted tumour sequencing test in 15 patients (9.9%), and HER2 positivity (IHC 3 + or IHC 2+/FISH positive) was detected in 21 patients (13.8%). The overall percent agreement, positive percent agreement, negative percent agreement and Cohen's kappa between ERBB2 CNA and HER2 status were 94.7%, 66.7%, 99.2% and 0.75, respectively. Progression-free survival for trastuzumab therapy in patients with ERBB2 AMP was significantly longer than that in patients with no ERBB2 AMP detected by the targeted tumour sequencing test (median 14 months vs. 4 months, P = 0.007). Treatment response to trastuzumab therapy was reduced in patients with ERBB2 AMP and concomitant CNAs of genes in HER2 DPs. One patient with ERBB2 AMP and concomitant CNAs of genes in HER2 DPs achieved a durable response to trastuzumab deruxtecan as fourth-line therapy. CONCLUSIONS: A targeted tumour sequencing test is a reliable modality for identifying HER2-positive GC. ERBB2 AMP and concomitant genetic alterations detected through the targeted tumour sequencing test are potential indicators of treatment response to trastuzumab therapy. The targeted tumour sequencing test has emerged as a plausible candidate for companion diagnostics to determine indications for anti-HER2 therapy in the era of precision medicine for GC.

DOI： 10.1186/s12885-024-12482-5

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DOI： 10.1245/s10434-024-15270-4

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BACKGROUND/AIM: NAD(P)H dehydrogenase [quinone] 1 (NQO1), an antioxidant enzyme, confers resistance to anticancer agents. NQO1 C609T is a single-nucleotide polymorphism associated with reduced protein expression in the non-neoplastic esophageal squamous epithelium (ESE). This study aimed to investigate immunohistochemical NQO1 expression in non-neoplastic ESE and to elucidate its prognostic significance in patients with esophageal squamous cell carcinoma (ESCC) undergoing neoadjuvant therapy followed by esophagectomy. MATERIALS AND METHODS: NQO1 expression in non-neoplastic ESE was determined in surgical specimens from 83 patients with ESCC using immunohistochemistry. The association between NQO1 expression and clinicopathological factors, and the prognostic significance of NQO1 expression for relapse-free survival (RFS) were statistically evaluated. RESULTS: Patients with complete loss or weak NQO1 expression and patients with moderate or strong NQO1 expression were classified into the NQO1-negative (n=29) and NQO1-positive (n=54) groups, respectively. The downstaging of T classification status after neoadjuvant therapy was significantly more frequent in the NQO1-negative group than in the NQO1-positive group (59% vs. 33%; p=0.036). The NQO1-negative group had significantly more favorable RFS than the NQO1-positive group (p=0.035). Multivariate survival analysis demonstrated that NQO1 negative expression had a favorable prognostic impact on RFS (HR=0.332; 95%CI=0.136-0.812; p=0.016). CONCLUSION: Immunohistochemical evaluation of NQO1 expression in non-neoplastic ESE has clinical utility for predicting patient prognosis after neoadjuvant therapy followed by esophagectomy and might be helpful for selecting candidates for adjuvant therapy to treat ESCC.

DOI： 10.21873/anticanres.16993

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BACKGROUND: The clinical impact of adjuvant chemotherapy after resection for adenocarcinoma arising from intraductal papillary mucinous neoplasia is unclear. The aim of this study was to identify factors related to receipt of adjuvant chemotherapy and its impact on recurrence and survival. METHODS: This was a multicentre retrospective study of patients undergoing pancreatic resection for adenocarcinoma arising from intraductal papillary mucinous neoplasia between January 2010 and December 2020 at 18 centres. Recurrence and survival outcomes for patients who did and did not receive adjuvant chemotherapy were compared using propensity score matching. RESULTS: Of 459 patients who underwent pancreatic resection, 275 (59.9%) received adjuvant chemotherapy (gemcitabine 51.3%, gemcitabine-capecitabine 21.8%, FOLFIRINOX 8.0%, other 18.9%). Median follow-up was 78 months. The overall recurrence rate was 45.5% and the median time to recurrence was 33 months. In univariable analysis in the matched cohort, adjuvant chemotherapy was not associated with reduced overall (P = 0.713), locoregional (P = 0.283) or systemic (P = 0.592) recurrence, disease-free survival (P = 0.284) or overall survival (P = 0.455). Adjuvant chemotherapy was not associated with reduced site-specific recurrence. In multivariable analysis, there was no association between adjuvant chemotherapy and overall recurrence (HR 0.89, 95% c.i. 0.57 to 1.40), disease-free survival (HR 0.86, 0.59 to 1.30) or overall survival (HR 0.77, 0.50 to 1.20). Adjuvant chemotherapy was not associated with reduced recurrence in any high-risk subgroup (for example, lymph node-positive, higher AJCC stage, poor differentiation). No particular chemotherapy regimen resulted in superior outcomes. CONCLUSION: Chemotherapy following resection of adenocarcinoma arising from intraductal papillary mucinous neoplasia does not appear to influence recurrence rates, recurrence patterns or survival.

DOI： 10.1093/bjs/znae100

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OBJECTIVES: De novo malignancy (DNM) is a major cause of death in long-term recipients of liver transplantation (LT). We herein report our experience with DNM after living-donor LT (LDLT). PATIENTS AND METHODS: A total of 111 LDLT procedures were performed in our institute from 1999 to 2022. Among them, 70 adult (>13 years old) LDLT recipients who survived for more than 1 year were included in this study. RESULTS: During a median follow-up of 146 (range, 12-285) months, 7 out of 70 recipients developed 8 DNMs, including lung cancer in 4, post-transplant lymphoproliferative disease in 3, and skin cancer in 1. One patient developed metachronal skin cancer and post-transplant lymphoproliferative disease. The pre-LT smoking history rate in patients with DNM was higher than in patients without DNM (P = .004). The survival time after DNM was 6 (1-166) months. Only 2 patients underwent R0 resection. DNM did not recur during follow-up. Other patients who underwent R1 resection and/or chemotherapy and/or radiotherapy all died due to DNMs during the follow-up. The cumulative DNM incidence was 3.5% at 10 years and 18.4% at 20 years after LDLT. The cumulative survival rate in patients with DNM was significantly worse than that in patients without DNM after LDLT (P = .049). CONCLUSION: The survival rate of patients with DNM was lower than that of those without DNM. A pre-LT smoking history is a risk factor for DNM. R0 resection is effective for improving the prognosis of patients with DNM. Regular cancer screening is important for detecting DNM early after LDLT.

DOI： 10.1016/j.transproceed.2024.02.015

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OBJECTIVE: The aim of the present study was to compare long-term post-resection oncological outcomes between A-IPMN and PDAC. SUMMARY BACKGROUND DATA: Knowledge of long term oncological outcomes (e.g recurrence and survival data) comparing between adenocarcinoma arising from intraductal papillary mucinous neoplasms (A-IPMN) and pancreatic ductal adenocarcinoma (PDAC) is scarce. METHODS: Patients undergoing pancreatic resection (2010-2020) for A-IPMN were identified retrospectively from 18 academic pancreatic centres and compared with PDAC patients from the same time-period. Propensity-score matching (PSM) was performed and survival and recurrence were compared between A-IPMN and PDAC. RESULTS: 459 A-IPMN patients (median age,70; M:F,250:209) were compared with 476 PDAC patients (median age,69; M:F,262:214). A-IPMN patients had lower T-stage, lymphovascular invasion (51.4%vs. 75.6%), perineural invasion (55.8%vs. 71.2%), lymph node positivity (47.3vs. 72.3%) and R1 resection (38.6%vs. 56.3%) compared to PDAC(P<0.001). The median survival and time-to-recurrence for A-IPMN versus PDAC were 39.0 versus19.5months (P<0.001) and 33.1 versus 14.8months (P<0.001), respectively (median follow-up,78 vs.73 months). Ten-year overall survival for A-IPMN was 34.6%(27/78) and PDAC was 9%(6/67). A-IPMN had higher rates of peritoneal (23.0 vs. 9.1%, P<0.001) and lung recurrence (27.8% vs. 15.6%, P<0.001) but lower rates of locoregional recurrence (39.7% vs. 57.8%; P<0.001). Matched analysis demonstrated inferior overall survival (P=0.005), inferior disease-free survival (P=0.003) and higher locoregional recurrence (P<0.001) in PDAC compared to A-IPMN but no significant difference in systemic recurrence rates (P=0.695). CONCLUSIONS: PDACs have inferior survival and higher recurrence rates compared to A-IPMN in matched cohorts. Locoregional recurrence is higher in PDAC but systemic recurrence rates are comparable and constituted by their own distinctive site-specific recurrence patterns.

DOI： 10.1097/SLA.0000000000006272

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BACKGROUND: Recent advances in treatment are expected to bring a cure to more patients with gastric cancer (GC). Focusing on the risk of death from other diseases (DOD) has become a crucial issue in patients cured of GC. The aim of this study was to elucidate the risk factors for DOD in patients who underwent curative gastrectomy with lymph node dissection for GC. METHODS: We enrolled 810 patients who underwent curative gastrectomy with lymph node dissection for GC from January 1990 to December 2014 and had no recurrence or death of GC until December 2019. We investigated the risk factors for DOD defined as death excluding death from a malignant neoplasm, accident, or suicide after gastrectomy, focusing on the perioperative characteristics at gastrectomy. RESULTS: Among 315 deaths from any cause, 210 died from diseases other than malignancy, accidents and suicide. The leading cause of DOD was pneumonia in 54 patients (25.7%). The actual survival period in 167 patients (79.5%) with DOD was shorter than their estimated life expectancy at gastrectomy. Multivariate analysis revealed that a high Charlson Comorbidity Index score (score 1-2: hazard ratio [HR] 2.192, 95% confidence interval [CI] 1.713-2.804, P < 0.001 and score ≥ 3: HR 4.813, 95% CI 3.022-7.668, P < 0.001), total gastrectomy (HR 1.620, 95% CI 1.195-2.197, P = 0.002) and the presence of postoperative complications (HR 1.402, 95% CI 1.024-1.919, P = 0.035) were significant independent risk factors for DOD after gastrectomy for GC, in addition to age of 70 years or higher, performance status of one or higher and body mass index less than 22.0 at gastrectomy. CONCLUSIONS: Pneumonia is a leading cause of DOD after curative gastrectomy and lymph node dissection for GC. Paying attention to comorbidities, minimizing the choice of total gastrectomy and avoiding postoperative complications are essential to maintain the long-term prognosis after gastrectomy.

DOI： 10.1186/s12893-024-02313-6

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DOI： 10.1093/bjs/znad417

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

症例は61歳,男性。閉塞性黄疸で発症し,切除可能膵頭部癌と診断し,亜全胃温存膵頭十二指腸切除術を施行した。術後5-FUの肝灌流化学療法を行い,引き続きgemcitabine(GEM)療法を6ヵ月間施行した。術後1年6ヵ月のCTで肝S6に肝転移が出現し,肝部分切除術を施行した。病理診断では膵癌肝転移であった。術後にGEM+S-1療法を1年間行い,S-1単独療法に切り替え約6ヵ月間施行した。初回手術後4年のCTで右肺に2ヶ所の肺転移を認めた。S-1療法を2ヵ月間施行後に右肺部分切除術を施行した。術後にGEM+nab-paclitaxel療法を開始したが,初回手術後5年のCTで胸膜播種が出現した。modified FOLFIRINOX療法へ変更し8ヵ月治療を継続したが,CTで横隔膜にも播種性病変が出現した。病変に緩和照射を行ったが,病状は徐々に進行した。初回手術から6年3ヵ月で死亡したが,再発後約5年の長期生存を得た。(著者抄録)

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The patient was a 61-year-old man with a diagnosis of carcinoma of the pancreatic head. Abdominal computed tomography( CT)showed no distant metastasis, and he underwent subtotal stomach-preserving pancreatoduodenectomy. Immediately after surgery, he received liver perfusion chemotherapy with 5-fluorouracil followed by systemic gemcitabine. Eighteen months after surgery, CT revealed liver metastasis in the S6 segment, and partial hepatectomy was performed. The pathological diagnosis was liver metastasis of pancreatic cancer. Postoperatively, the patient was treated with gemcitabine and S-1 therapy for 1 year and then switched to S-1 monotherapy for about 6 months. Four years after the initial surgery, CT showed 2 metastases in the right lung. After 2 months of S-1 monotherapy, wedge resection of the upper and lower lobes of the right lung was performed. Gemcitabine and nab-paclitaxel therapy were administered, after the metastasectomy, but pleural dissemination appeared on CT 5 years after the initial surgery. Modified FOLFIRINOX therapy was started and continued for 8 months, but CT revealed further disseminated lesions in the diaphragm. Palliative irradiation was provided, but the disease gradually progressed. After multidisciplinary treatment, the patient survived for 6 years and 3 months after the initial surgery.

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今回,2回の肝内再発巣切除を施行して長期生存が得られた肝嚢胞腺癌の1例を経験したので報告する。症例は72歳,男性。肝S3を主座とする肝嚢胞腺癌に対して,肝左葉切除+肝外胆管切除+リンパ節郭清を施行した。術後7年9ヵ月目のCTで単発の肝内再発を指摘され,肝S5部分切除を施行した。初回手術から15年7ヵ月目には再度S5に肝内再発を来し,肝部分切除術を施行した。これらの肝再発巣は,病理組織学的に肝嚢胞腺癌の転移であることが確認された。以降は再発を認めず,初回手術から21年6ヵ月を経過した現在,生存中である。本症例の経験および文献的考察から,肝嚢胞腺癌の肝内再発に対して,再発巣切除は有用な治療選択肢の一つとなる可能性があることが示された。(著者抄録)

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症例は87歳,女性。左乳房腫瘤が徐々に増大したため近医を受診した。皮膚浸潤を伴う左乳癌と診断され,当科を受診した。精査の結果,左乳癌に加え,上行結腸癌と胸部大動脈瘤を認めた。上行結腸癌(cT4bN1bM0,cStage IIIc,大腸癌取扱い規約第9版),左乳癌(cT3N0M0,cStage IIB,乳癌取扱い規約第18版),胸部大動脈瘤(Stanford B型)と診断した。まず,胸部大動脈瘤に対して胸部大動脈ステント内挿術,両側鎖骨下動脈バイパス術を施行した。その6日後,上行結腸癌に対して結腸右半切除術,D2郭清を施行した。病理組織診断の結果,pT3N0M0,pStage IIaであった。上行結腸癌手術の2ヵ月後に左乳癌に対して左乳房全切除術,全層植皮術を施行した。病理組織診断の結果,pT3N0M0,pStage IIBであった。上行結腸癌術後20ヵ月,左乳癌術後18ヵ月無再発生存中である。(著者抄録)

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症例は57歳,男性。嚥下困難と嘔吐の精査で進行食道扁平上皮癌(Ut,cT3N0M0)と診断した。経鼻栄養チューブによる栄養管理を行いながら,術前docetaxel,cisplatin,5-fluorouracil併用(DCF)療法を実施した。1コース終了後に気管浸潤を認めた(cT4bN0M0)。根治的化学放射線療法(CF療法併用,照射60Gy)を実施し,気管浸潤の解除を認めた(cT3N0M0)。生検では癌の検出はなかったが,肉眼的に遺残が疑われ狭窄の悪化も認められた。安全に根治切除が可能と判断し,右開胸食道切除術(D0),胸骨後経路胃管再建を行った。病理診断ではpT1bN0M0であった。術後補助治療は実施せず,術後5年が経過して無再発生存中である。術前治療中の注意深い治療効果判定と適切な治療選択により,術前DCF療法不応例であっても根治の可能性を逃さないことが重要である。(著者抄録)

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症例は66歳,男性。発熱と腹痛の精査で肝機能障害を認めた。精査で膵内胆管の不整な壁肥厚と狭窄を認め,遠位胆管癌と診断された。根治切除の方針となり,亜全胃温存膵頭十二指腸切除術を施行された。肝側胆管切離断端は切離限界まで追加切除を行ったが,術中迅速組織診断で上皮内癌陽性であった。病理所見では膵内胆管に浸潤癌が存在し,そこより肝側の切除胆管全域に上皮内癌を認めた。また,No.13aリンパ節に転移を1個認めた。最終診断はpT3N1M0,pStage IIBであった。術後補助化学療法として1年間,S-1を内服した。術後5年目に胆管空腸吻合部に乳頭状隆起性病変を認め,生検で腺癌の診断であった。S-1内服を再開し,その後は腫瘍の増大を認めていない。術後9年1ヵ月現在,生存中である。(著者抄録)

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症例は58歳,女性。体重減少を主訴に来院した。腹部CT検査で胆管および膵管の拡張と膵管内に造影される壁在結節が認められ,膵管内乳頭粘液性腫瘍(IPMN)と診断された。内視鏡的逆行性胆管造影(ERCP)および胆道鏡で総胆管とIPMNとの間の瘻孔が確認された。IPMNの総胆管穿破と診断し,手術適応と判断した。術前待機中に急激な肝胆道系酵素の増加が認められ,ERCPを施行したところ粘液により総胆管が閉塞していたため,内視鏡的経鼻胆道ドレナージ(ENBD)チューブを挿入した。連日の洗浄によりチューブ開存を維持することで,肝機能障害は改善した。膵全摘術,脾臓合併切除,領域リンパ節郭清を施行した。病理診断は混合型浸潤性膵管内乳頭粘液性腺癌であった。術後18ヵ月が経過した現在,無再発生存している。胆管穿破を伴うIPMNに対する胆道ドレナージは,排液量の観察と洗浄が可能なENBDが妥当である。(著者抄録)

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An 87-year-old woman with a gradually enlarging mass in her left breast, diagnosed as having left-sided breast cancer with skin invasion by a local practitioner, was referred to our hospital. Computed tomography revealed ascending colon cancer with abdominal wall invasion and a thoracic aortic aneurysm(Stanford type B), in addition to breast cancer with skin invasion. A thoracic endovascular aortic repair and bypass surgery between the subclavian arteries were both performed for the thoracic aortic aneurysm. After 6 days, a right hemicolectomy and D2 lymphadenectomy were performed for the ascending colon cancer. A postoperative pathological diagnosis of pT3N0M0, pStage Ⅱa, was made. A total left mastectomy with a full-thickness skin graft for left breast cancer was performed after 2 months following the ascending colon cancer surgery. The postoperative pathological diagnosis was pT3N0M0, pStage ⅡB. No evidence of local recurrence or distant metastasis of the ascending colon cancer has been observed at 20 months postoperatively, or of the breast cancer after 18 months following surgery.

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

We report a case of biliary cystadenocarcinoma in which long-term survival was achieved after 2 operations for intrahepatic recurrence. A 72-year-old man with biliary cystadenocarcinoma located mainly in segment 3 of the liver underwent left hepatectomy, extrahepatic bile duct resection, and lymph node dissection. Seven years and 9 months after the initial resection, he underwent partial liver resection(segment 5)for intrahepatic recurrence detected by computed tomography. Fifteen years and 7 months after the initial resection, he underwent repeat partial resection of the liver(segment 5)for intrahepatic recurrence. Histologically, these tumors were confirmed to be recurrence of biliary cystadenocarcinoma. He remains alive and well with no further recurrence 21 years and 6 months after the initial resection. This case and a literature review suggest that hepatic resection is a useful treatment option for intrahepatic recurrence of biliary cystadenocarcinoma.

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BACKGROUND: This study aimed to evaluate the adequate extent of regional lymphadenectomy according to tumor location and the impact of number-based nodal classification on survival in patients with non-ampullary duodenal adenocarcinoma (NADAC). METHODS: A total of 85 patients with NADAC who underwent surgery were enrolled. The frequency of metastasis was calculated for each node group in the respective tumor locations for 63 patients who underwent lymphadenectomy for pT2-pT4 tumor. RESULTS: The frequency of metastasis in the pancreaticoduodenal (nos. 13 and 17) and superior mesenteric artery (no. 14) nodes was high (16.7 %-52.3 %) regardless of tumor location. Metastasis in the perigastric (nos. 3 and 4d) and right celiac artery (no. 9) nodes was not uncommon (14.3 %-22.2 %) for tumors in the first portion. The frequency of metastasis in the pyloric (nos. 5 and 6) and the other peripancreaticoduodenal (nos. 8 and 12) nodes varied depending on tumor location but could not be ignored for staging. When these nodes were classified as regional nodes, the 5-year survival in patients with pN0, pN1 (1-2 positive nodes), and pN2 (≥3 positive nodes) were 82.9 %, 51.7 %, and 19.2 %, respectively (p < 0.001). pN classification independently predicted survival (pN1, p = 0.022; pN2, p < 0.001). CONCLUSIONS: Nos. 5, 6, 8, 12, 13, 14, and 17 nodes in all advanced NADAC and nos. 3, 4d, and 9 nodes in advanced NADAC in the first portion should be considered as regional nodes for accurate staging. The number-based nodal classification allows good patients' prognostic stratification.

DOI： 10.1016/j.ejso.2023.107122

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

A 58-year-old woman presented with a complaint of weight loss. Abdominal computed tomography showed dilatation of the biliary and pancreatic ducts and a mural nodule in the pancreatic duct. The diagnosis was intraductal papillary mucinous neoplasm(IPMN). Endoscopic retrograde cholangiopancreatography(ERCP)and cholangioscopy revealed a fistula between the common bile duct and the IPMN. A sudden increase in hepatobiliary enzymes was noted preoperatively. ERCP showed that the common bile duct was obstructed by mucus. A nasobiliary drainage tube was inserted into the bile duct endoscopically and kept open by daily tube washing, and the liver dysfunction improved. Total pancreatectomy, splenectomy, and regional lymph node dissection were performed. Histological examination confirmed that the primary tumor was mixed invasive intraductal papillary mucinous adenocarcinoma. The patient remains alive and well with no evidence of recurrence 18 months after resection.

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A 66-year-old man was referred to our hospital with fever and abdominal pain. CT showed a mass in the intrapancreatic bile duct but no wall thickness in the perihilar bile ducts. Neither regional lymphadenopathy nor distant metastasis was observed. Biliary cytology showed adenocarcinoma. The diagnosis was distal cholangiocarcinoma, and pancreatoduodenectomy was performed. Intraoperative frozen section examination of the ductal resection margins at the right and left hepatic ducts was positive for carcinoma in situ, and the operation ultimately completed with R1 resection. Histological examination confirmed a diagnosis of cholangiocarcinoma with superficial spread and a single positive lymph node. Adjuvant chemotherapy with S-1 was administered for 1 year. Anastomotic recurrence at the hepaticojejunostomy was found 5 years after resection; biopsy specimens revealed adenocarcinoma. Thereafter, S-1 chemotherapy was resumed, and the patient remains alive and well 9 years and 1 month after resection.

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Metastatic choroidal carcinoma is rare and generally has a poor prognosis. The present case report describes a case of choroidal metastasis from distal cholangiocarcinoma, which was successfully managed using stereotactic radiotherapy (SRT). A 67-year-old Japanese man underwent pancreaticoduodenectomy for distal cholangiocarcinoma. The pathological stage was T2N0M0 stage IIA, according to the Union for International Cancer Control 8th edition. After surgery, the patient received adjuvant chemotherapy with oral TS-1® for 1 month. A total of 2 months after surgery, the patient was readmitted to hospital due to decreased visual acuity. Fundoscopy revealed a macular hole in the right eye that accounted for the decreased visual acuity. Additionally, Goldmann three-mirror contact lens examination revealed a 4-mm choroidal mass with a yellowish color situated at a considerable distance from the optic nerve. Magnetic resonance imaging revealed an enhanced choroidal mass. Based on the findings of ophthalmologic examinations and the patient's history of cholangiocarcinoma, they were diagnosed with choroidal metastasis from distal cholangiocarcinoma. SRT was administered at a total dose of 40 Gy divided into 8 Gy fractions. A total of 1 year after SRT, the patient achieved complete remission without decreased visual acuity. The patient remains alive and in good health without recurrence, 4 years after the diagnosis of choroidal metastasis. To the best of our knowledge, this is the second reported case of intraocular metastasis from cholangiocarcinoma. In conclusion, SRT may provide an opportunity to control metastatic choroidal carcinoma without decreasing visual acuity.

DOI： 10.3892/ol.2023.14004

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Alterations in KRAS, CDKN2A (p16), TP53, and SMAD4 genes have been major drivers of pancreatic carcinogenesis. The clinical course of patients with pancreatic cancer in relation to these driver alterations has not been fully characterised in large populations. We hypothesised that pancreatic carcinomas with different combinations of KRAS mutation and aberrant expression of CDKN2A, p53, and SMAD4 might show distinctive recurrence patterns and post-operative survival outcomes. To test this hypothesis, we utilised a multi-institutional cohort of 1,146 resected pancreatic carcinomas and assessed KRAS mutations by droplet digital polymerase chain reaction and CDKN2A, p53, and SMAD4 expression by immunohistochemistry. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) for disease-free survival (DFS) and overall survival (OS) were computed according to each molecular alteration and the number of altered genes using the Cox regression models. Multivariable competing risks regression analyses were conducted to assess the associations of the number of altered genes with specific patterns of recurrence. Loss of SMAD4 expression was associated with short DFS (multivariable HR, 1.24; 95% CI, 1.09-1.43) and OS times (multivariable HR, 1.27; 95% CI, 1.10-1.46). Compared to cases with 0-2 altered genes, cases with three and four altered genes had multivariable HRs for OS of 1.28 (95% CI, 1.09-1.51) and 1.47 (95% CI, 1.22-1.78), respectively (ptrend  < 0.001). Patients with an increasing number of altered genes were more likely to have short DFS time (ptrend  = 0.003) and to develop liver metastasis (ptrend  = 0.006) rather than recurrence at local or other distant sites. In conclusion, loss of SMAD4 expression and an increasing number of altered genes were associated with unfavourable outcomes in pancreatic cancer patients. This study suggests that the accumulation of the four major driver alterations can confer a high metastatic potential to the liver, thereby impairing post-operative survival among patients with pancreatic cancer.

DOI： 10.1002/cjp2.323

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BACKGROUND/AIM: Sphingosine-1-phosphate (S1P) is a pleiotropic, bioactive, lipid mediator, produced by sphingosine kinase 1 (SphK1). In this study, we evaluated the expression of phosphorylated SphK1 (pSphK1) in patients with pancreatic ductal adenocarcinoma (PDAC) and investigated its clinical significance. MATERIALS AND METHODS: A total of 111 patients who underwent curative-intent resection for PDAC were enrolled. We investigated pSphK1 (Ser-225) expression in surgically resected specimens of PDAC using immunohistochemistry. The patients were divided into two groups according to pSphK1 immunoreactive expression: a pSphK1-high group (n=63) and a pSphK1-low group (n=48). RESULTS: Logistic regression analyses revealed that lymphatic invasion (p=0.007) was a significantly independent factor associated with high pSphK1 immunoreactive expression. The pSphK1-high group showed significantly worse disease-specific survival (DSS) than the pSphK1-low group (5-year DSS rate, 19.6% vs. 58.7%; p=0.001). High pSphK1 immunoreactive expression (hazard ratio=2.547; 95% confidence interval= 1.434-4.527; p=0.001) was an independent prognostic factor for DSS. CONCLUSION: High pSphK1 expression is independently associated with lymphatic invasion and unfavorable prognosis in PDAC patients. Thus, the SphK1-S1P axis may be important in mechanisms of tumor progression, such as lymphatic invasion, in PDAC patients.

DOI： 10.21873/anticanres.16584

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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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Language：Japanese   Publisher：新潟医学会  

重症胆道感染症から敗血症性ショックに至った症例に対してエンドトキシン吸着療法(polymyxin-direct hemoperfusion:PMX-DHP)を行い,急性期から脱却後に手術を施行し得た2例を経験したので報告する.症例1は79歳の男性で,発熱と呼吸困難を主訴に救急外来を受診した.呼吸数36回/分,経皮的動脈血酸素飽和度81%(room air),心拍数71回/分,血圧85/61mmHgとショック状態であった.腹部造影CT検査で胆嚢結石と総胆管の拡張を認め,総胆管結石による重症急性胆管炎と診断した.気管内挿管と急速輸液,ノルアドレナリンの持続静注を開始し,経皮経肝胆道ドレナージを行なったが,敗血症性ショックが遷延したためPMX-DHPを施行した.PMX-DHP開始後4時間程度で循環動態は安定し,ノルアドレナリンの投与を終了した.急性胆管炎発症から3病日目に人工呼吸器管理を終了し,15病日目に内視鏡下に総胆管結石を採石した.29病日目に自宅へ退院となった.発症から3ヵ月後に腹腔鏡下胆嚢摘出術を施行した.術後2年2ヵ月が経過した現在,胆道感染症の再発なく経過している.症例2は86歳の女性で,大動脈弁置換術後のため入院加療中であった.術後21病日目に発熱し,呼吸数34回/分,経皮的動脈血酸素飽和度96%(酸素8L/分投与下),心拍数125回/分,血圧85/41mmHgとショック状態となった.腹部造影CT検査で腫大した胆嚢と周囲の脂肪織濃度の上昇を認め,重症急性胆嚢炎と診断した.急速輸液,ノルアドレナリンの持続静注を開始し,経皮経肝胆嚢ドレナージを施行した.敗血症性ショックが遷延したためPMX-DHPを施行し,血圧は上昇傾向となった.急性胆嚢炎発症から3病日目にノルアドレナリンの投与を終了できた.46病日目にリハビリ目的に他院へ転院となった.発症から3ヵ月後に開腹下胆嚢摘出術を施行した.術後1年6ヵ月が経過した現在,胆道感染症の再発なく経過している.重症胆道感染症により循環動態が不安定な症例では,PMX-DHPは支持療法として治療選択肢の1つになり得る.(著者抄録)

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DOI： 10.1245/s10434-023-13418-2

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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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DOI： 10.1245/s10434-023-13440-4

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

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

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

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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: 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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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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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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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：新潟医学会  

【目的】スフィンゴシン-1-リン酸(S1P)は様々な生理活性を持つスフィンゴ脂質であり,炎症や発癌に関与していると言われている.潰瘍性大腸炎術後回腸嚢炎は晩期合併症として注目されているが,原因については不明な点が多い.本研究では,S1Pと回腸嚢炎の関連を明らかにすることを目的とした.【対象と方法】2020年7月～2021年2月に潰瘍性大腸炎術後,回腸嚢から内視鏡的あるいは手術により組織生検が行われた6名を対象とした.臨床データ(採血結果,回腸嚢炎重症度,消化管内視鏡検査等)をカルテから後方視的に解析した.回腸嚢炎の診断は,厚生労働科学研究費補助金難治性疾患政策研究事業による「潰瘍性大腸炎・クローン病診断基準・治療指針」に準じた.回腸嚢組織における質量分析によるS1P測定,および抗リン酸化S1P産生酵素(pSphK1)抗体を用いた免疫組織化学染色を行った.回腸嚢炎の重症度とS1P値,抗pSphK1抗体免疫組織化学染色の関連について検討した.【結果】対象6名の内訳は,男性5名,女性1名,年齢の中央値は45歳(範囲:33-70歳)であった.回腸嚢の内視鏡所見として,1例は回腸嚢炎なし(正常),2例は軽度,3例は中等度であった.対象6例のS1P測定値(中央値)は0.2pmol/mg(範囲:0.1-0.8pmol/mg)であった.採血データで高度の炎症を伴った中等度症例のS1P値が高値を示していた.免疫組織化学染色の結果では,内視鏡的に回腸嚢炎の所見を認めた5例のうち4例で抗pSphK1抗体陽性が陽性であった.【結論】脂質メディエーターであるS1Pが,潰瘍性大腸炎術後回腸嚢炎の炎症増悪に関与している可能性が示唆された.(著者抄録)

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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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BACKGROUND: As the number of long-term survivors after organ transplantation increases, malignancy has become a problem as a late complication. We herein report a case of endometrial cancer during the follow-up of pancreas transplantation after kidney transplantation. CASE PRESENTATION: A 49-year-old woman was diagnosed with endometrial cancer. The patient had developed type 1 diabetes at 8 years old and started insulin treatment, and at 29 years old, she started hemodialysis for diabetic nephropathy. At 31 years old, she received living donor kidney transplantation and withdrew from dialysis. Hypoglycemia unawareness began to occur frequently from around 36 years old, and at 48 years old, the patient underwent deceased donor pancreas transplantation after kidney transplantation and achieved insulin independence. At 49 years old, she was diagnosed with endometrial cancer. Surgical treatment (total abdominal hysterectomy with left salpingo-oophorectomy) was performed. The pathologic diagnosis was confirmed as stage 1A uterine endometrioid carcinoma grade 1. The postoperative course was uneventful. She was discharged from our hospital on postoperative day 8. There has been no evidence of recurrence and/or metastasis of endometrial cancer for 16 months since the surgery. CONCLUSIONS: Carcinogenesis after pancreas transplantation may be a lethal late complication. It is important to carry out regular screening examinations with carcinogenesis in mind.

DOI： 10.1016/j.transproceed.2021.12.021

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BACKGROUND: Evaluation of an experimental and preclinical islet transplantation (IsletTx) model to elucidate associated clinical problems is vital. This study aimed to introduce a simple methodology for producing a swine autologous IsletTx model as a preliminary step in an allogeneic transplant experiment. METHODS AND MATERIALS: Twenty-seven pigs were included in the study. Total pancreatectomy (TP) was performed in 8 pigs (TP group), TP with autologous IsletTx in 9 (TP + IsletTx group), and distal pancreatectomy (DP) with autologous IsletTx in 10 (DP + IsletTx group). An open biopsy was performed on all pigs during postoperative day 14 using an infrared imaging (IRI) system. Laboratory data and postoperative survival were analyzed and compared according to the procedures done. RESULTS: Postoperative survival rate was significantly higher in the pigs with autologous IsletTx than in those without (P = .026). There were no significant differences in survival between the TP + IsletTx and DP + IsletTx groups (P = .746). Significant hyperglycemia was not observed in both groups, but the DP + IsletTx group remained relatively stable throughout the postoperative course. There were no differences in serum creatinine, aspartate aminotransferase, and alanine aminotransferase levels between the 2 groups. By selective liver lobe transplantation and administration of the IRI system, localization of the transplanted islets via open biopsy was achieved. CONCLUSIONS: We successfully developed an autologous IsletTx model and an open biopsy system using a swine model. This study will aid in the development of an allogeneic IsletTx experiment that may improve transplantation outcomes.

DOI： 10.1016/j.transproceed.2021.10.029

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BACKGROUND: Although monofilament mesh-based repair is a safe and effective procedure for incisional hernia (IH) in organ transplant patients, there is no definite evidence of IH treatment for patients with graft rejection and enhanced immunosuppressive therapy. We report a successful case of large IH repair using an autologous thigh muscle fascia sheet in a kidney transplant patient. CASE PRESENTATION: A 69-year-old man had IH from the incision of kidney transplantation, which was performed 6 years ago. He had a large right lower abdominal distension hanging down to the inguinal portion. A computed tomography scan revealed a large IH with a maximum abdominal defect diameter of 15 cm. The hernia sac contained the intestine, colon, and transplanted kidney, which had pulled out along with the retroperitoneum and protruded into the abdominal wall. He had chronic active acute antibody-mediated rejection, which required frequent steroid pulse therapy and additional or adjusted immunosuppressive drugs. After total circumferential exposure of the hernia sac and abdominal fascia, the abdominal wall defect was closed using a horizontal mattress suture. The sutured line was covered with a thigh muscle fascia sheet harvested from the patient's right femur and attached to the closed fascia. He was discharged on postoperative day 13 without any complications, and no IH recurrence was observed 10 months after surgery. CONCLUSIONS: Hernia repair using autologous tissue could be a treatment option for post-transplant IH with a higher risk of infection.

DOI： 10.1016/j.transproceed.2021.09.076

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DOI： 10.1016/j.tpr.2022.100095

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Language：Japanese   Publisher：(一財)日本消化器病学会  

70歳男性.精索腫瘍,限局性腹膜播種に対し,腫瘍摘出術および播種巣切除を施行し,遺伝子検査で精索原発滑膜肉腫と診断された.術後7年目に突然の腹部膨満感と腹痛で救急搬送され,内部に出血をともなう17cm大の腫瘍を網嚢内に認めた.緊急で腫瘍摘出術および結腸部分切除を施行し,遺伝子検査で精索原発滑膜肉腫の腹腔内再発と診断された.これまで精索原発滑膜肉腫の本邦報告例はなく,文献的考察を加えて報告する.(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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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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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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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：(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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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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AIM: Sphingosine-1-phosphate (S1P) and ceramide are bioactive sphingolipids known to be important in regulating numerous processes involved in cancer progression. The aim of this study was to determine the absolute levels of sphingolipids in hepatocellular carcinoma (HCC) utilizing data obtained from surgical specimens. In addition, we explored the clinical significance of S1P in patients with HCC and the biological role of S1P in HCC cells. METHODS: Tumors and normal liver tissues were collected from 20 patients with HCC, and sphingolipids were measured by mass spectrometry. The Cancer Genome Atlas (TCGA) cohort was utilized to evaluate gene expression of enzymes related to sphingolipid metabolism. Immunohistochemistry of phospho-sphingosine kinase 1 (SphK1), an S1P-producing enzyme, was performed for 61 surgical specimens. CRISPR/Cas9-mediated SphK1 knockout cells were used to examine HCC cell biology. RESULTS: S1P levels were substantially higher in HCC tissue compared with normal liver tissue. Levels of other sphingolipids upstream of S1P in the metabolic cascade, such as sphingomyelin, monohexosylceramide and ceramide, were also considerably higher in HCC tissue. Enzymes involved in generating S1P and its precursor, ceramide, were found in higher levels in HCC compared with normal liver tissue. Immunohistochemical analysis found that phospho-SphK1 expression was associated with tumor size. Finally, in vitro assays indicated that S1P is involved in the aggressiveness of HCC cells. CONCLUSIONS: Sphingolipid levels, including S1P and ceramide, were elevated in HCC compared with surrounding normal liver tissue. Our findings suggest S1P plays an important role in HCC tumor progression, and further examination is warranted.

DOI： 10.1111/hepr.13625

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DOI： 10.1007/s00268-021-05991-y

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DOI： 10.1007/s10346-021-01680-y

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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/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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Language：Japanese   Publisher：金原出版(株)  

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DOI： 10.1245/s10434-020-09184-0

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

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DOI： 10.1111/cas.14823

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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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Web of Science

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DOI： 10.11405/nisshoshi.118.1130

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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   Publishing type：Research paper (scientific journal)  

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 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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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：(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：日本消化器病学会-甲信越支部  

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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: The role of surgery in the management of primary cystic duct carcinoma (CDC) remains unclear especially in advanced disease. This study aimed to evaluate long-term outcomes in patients undergoing surgery for primary CDC. METHODS: From a multi-institutional database, we identified 41 patients who underwent surgery for primary CDC, defined as a part of gallbladder carcinoma with the tumor centre located in the cystic duct. RESULTS: Of the 41 patients, 31 (75.6%) underwent preoperative biliary drainage for jaundice. Twenty-eight (68.3%) patients underwent extensive resection including major hepatectomy (n = 21), pancreaticoduodenectomy (n = 4), or both procedures (n = 3). Thirty-four (82.9%) patients had ≥ pT3 tumor, while 31 (75.6%) patients had involvement of contiguous organs/structures. Nodal and distant metastasis was found in 26 (63.4%) and 7 (17.1%) patients, respectively. Most patients (90.2%) had perineural invasion. Median overall survival was 23.7 months in all 41 patients. Factors independently associated with both overall and disease-specific survival were pN (P = 0.003 and P = 0.007, respectively) and pM (P = 0.003 and P = 0.013, respectively) classification. Median survival was 75.3, 17.7, and 5.2 months for patients with pN0M0 (n = 14), pN1/2pM0 or pN0pM1 (n = 21), and pN1/2pM1 (n = 6) disease, respectively (P < 0.001). CONCLUSIONS: Primary CDC is characterized by locally advanced disease with aggressive histopathological characteristics at surgery, leading to extensive resection during treatment. Surgery provides potential benefits for patients with pN0pM0 disease, whereas pN1/2 and/or pM1 status appear to have strong adverse effects on survival.

DOI： 10.1007/s00268-020-05656-2

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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：日本胆道学会  

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

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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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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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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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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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Language：Japanese   Publisher：金原出版(株)  

正中弓状靱帯(MAL)による腹腔動脈起始部狭窄を伴う手術11例を対象に、臨床的検討を行った。その結果、MALによる腹腔動脈起始部狭窄の診断の契機は、膵頭十二指腸切除術(PD)前のdynamic CT検査6例、膵十二指腸動脈瘤形成・破裂3例、食後の慢性腹痛1例、肝細胞癌診断時のdynamic CT検査1例であった。MALを切離した症例は8例で、手術はPD2例、亜全胃温存PD1例、TAE3例、肝右葉切除術1例、なし1例であった。MAL切離は周術期合併症なく安全に施行でき、手術後も腹腔動脈還流領域の虚血に起因する合併症を認めなかった。MALを切離しなかった症例は3例で、手術は亜全胃温存PDであった。3例とも腹腔動脈起始部狭窄に起因する症状はなかった。亜全胃温存PD後に2例に腹腔動脈還流領域の虚血に起因する合併症を認めた(肝外側区域の梗塞1例、膵腸吻合部狭窄1例)。MALによる腹腔動脈起始部狭窄に対しMAL切離は有用と考えられた。

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BACKGROUND: There is no comprehensive agreement concerning the overall performance of radical resection for T1b gallbladder cancer (GBC). This research focused on addressing whether T1b GBC may spread loco-regionally and whether radical resection is necessary. METHODS: A retrospective analysis was conducted of 1032 patients with GBC who underwent surgical resection at our centre and its affiliated institutions between January 1982 and December 2018. A total of 47 patients with T1b GBC, 29 (62%) of whom underwent simple cholecystectomy and 18 (38%) of whom underwent radical resection with regional lymph node dissection, were enrolled in the study. RESULTS: GBC was diagnosed pre-operatively in 16 patients (34%), whereas 31 patients (66%) had incidental GBC. There was no blood venous or perineural invasion in any patient on histology evaluation, except for lymphatic vessel invasion in a single patient. There were no metastases in any analysed lymph nodes. The open surgical approach was more prevalent among the 18 patients who underwent radical resection (open in all 18 patients) than among the 29 patients who underwent simple cholecystectomy (open in 21; laparoscopic in 8) (P = 0.017). The cumulative 10- and 20-year overall survival rates were 65 and 25%, respectively. The outcome following simple cholecystectomy (10-year overall survival rate of 66%) was akin to that following radical resection (64%, P = 0.618). The cumulative 10- and 20-year disease-specific survival rates were 93 and 93%, respectively. The outcome following simple cholecystectomy (10-year disease-specific survival rate of 100%) was equivalent to that following radical resection (that of 86%, P = 0.151). While age (> 70 years, hazard ratio 5.285, P = 0.003) and gender (female, hazard ratio 0.272, P = 0.007) had a strong effect on patient overall survival, surgical procedure (simple cholecystectomy vs. radical resection) and surgical approach (open vs. laparoscopic) did not. CONCLUSIONS: Most T1b GBCs represent local disease. As pre-operative diagnosis, including tumour penetration of T1b GBC, is difficult, the decision of radical resection is justified. Additional radical resection is not required following simple cholecystectomy provided that the penetration depth is restricted towards the muscular layer and that surgical margins are uninvolved.

DOI： 10.1186/s12885-019-6507-2

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INTRODUCTION: Portosystemic collaterals (PsC) are a common finding in patients with cirrhosis who need liver transplantation (LT), and PsCs may cause several problems before and after LT. We report a case of successful surgical treatment of severe hepatic encephalopathy (HE) caused by PsC after living-donor LT (LDLT). CASE: A 71-year-old woman with hepatocellular carcinoma underwent LDLT for chronic hepatitis C virus infection at 64 years of age. The splenocaval collateral vein was ligated during LDLT to prevent portal flow steal. A recurrent episode of coma due to HE was triggered 7 years after LDLT and gradually became refractory to any drug treatments. Contrast-enhanced computed tomography revealed the development of the right gastroepiploic vein (RGEV), which flowed to the inferior vena cava via the inferior mesenteric vein (IMV). Owing to the chronic kidney disease (estimated glomerular filtration rate, 11-31 mL/min), interventional radiology (IVR) was not indicated, so surgical treatment was selected to treat the symptom. PsC was resected at the point of the RGEV and IMV, just before flowing into the IVC with vascular staplers. Antegrade portal blood flow was obtained by ultrasonography 2 days after surgery, and the patient was discharged from the hospital 26 days after the operation. After discharge, she has had no recurrent episode of HE. CONCLUSION: Surgical resection of the PsC was effective for treatment of HE caused by shunt flow after LDLT.

DOI： 10.1016/j.transproceed.2020.01.156

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A 68-year-old male patient received a living donor kidney transplantation 8 years earlier for end-stage kidney disease secondary to IgA nephropathy. His post-transplantation follow-up had been routinely performed with laboratory examinations, ultrasound, and computed tomography (CT). His kidney graft function had been excellent and stable, as shown by a baseline serum creatinine level of 1.0 mg/dL. At referral, regular follow-up ultrasound and CT showed allograft hydroureteronephrosis. He did not have any complaints, but his physical examination revealed right inguinal bulging that was 3.5 × 3.5 cm. Abdominal enhanced CT revealed transplant allograft hydroureteronephrosis due to ipsilateral herniation of ureteroneocystostomy into the right inguinal canal. His serum creatinine level was slightly elevated (1.1 mg/dL). Then, he underwent an open right inguinal hernia repair. Paraperitoneal allograft hydroureteronephrosis and bladder herniation was confirmed at surgery, and hernioplasty with polypropylene mesh reinforcement was successfully performed. The postoperative course was uneventful. He was discharged on the seventh day after surgery. Six weeks after surgery, CT revealed disappearance of allograft hydroureteronephrosis and no sign of inguinal hernia recurrence with the serum creatinine stable at 1.0 mg/dL. Transplant ureteral obstruction due to inguinal hernia is a rare complication after kidney transplantation. However, transplant ureter or bladder herniation should be considered in the differential diagnosis of graft hydroureteronephrosis for preventing allograft loss.

DOI： 10.1016/j.transproceed.2020.02.131

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DOI： 10.15684/FORMATH.19.002

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DOI： 10.1016/j.tpr.2020.100052

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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.

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

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   Publishing type：Research paper (scientific journal)  

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.

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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.

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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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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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DOI： 10.1111/cas.14291

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BACKGROUND: The cystic duct has been included in the staging classification scheme for gallbladder cancer since the 2010 publication of the AJCC Cancer Staging Manual (7th edition). To our knowledge, only seven other cases of adenocarcinoma arising in the remnant cystic duct following cholecystectomy have been reported in the English-language literature, and none has been reported as primary early-stage T1b remnant cystic duct cancer (CDC). We report, herein, a case of primary adenocarcinoma arising in the remnant cystic duct in a patient with history of laparoscopic cholecystectomy for gallstone disease. CASE PRESENTATION: An 81-year-old female presented with abdominal pain. Her medical history included a laparoscopic cholecystectomy for cholecystolithiasis two years prior. Jaundice was observed; imaging studies suggested that this was caused by choledocholithiasis. Blood chemistry findings showed severe liver dysfunction. Endoscopic retrograde cholangiography revealed haemobilia from the common bile duct with no evidence of choledocholithiasis. A bile sample showed Papanicolaou class IV cytology. As the extent of tumour spread was undetermined by abdominal ultrasonography and endoscopic ultrasonography, peroral cholangioscopy (POCS) was performed, which revealed tiny papillary lesions within the confluence of cystic duct, and fine granular lesions in the centre of bile ducts, signifying early-stage remnant CDC. Extrahepatic bile duct resection with regional lymphadenectomy was done. Histopathological findings revealed a 42-mm tubular adenocarcinoma originating from the remnant cystic duct with the considerable shallow spread across the extrahepatic bile ducts. It invaded the fibromuscular layer, with no lymphovascular or perineural invasion, no lymph node metastasis (13 nodes examined), and uninvolved surgical resection margin (R0 resection), and was staged as pT1bN0M0, Stage I. CONCLUSIONS: Primary early-stage T1b remnant CDC is an uncommon condition for which early diagnosis is challenging; if intraoperatively recognized, it can complicate surgery. Our experience of this case and an overview of the English literature suggest that POCS is an efficient tool to diagnosis this tumour and assess its spread along the extrahepatic bile ducts.

DOI： 10.1186/s12893-019-0647-9

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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：日本臨床外科学会  

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Language：Japanese   Publisher：(株)医学書院  

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Language：Japanese   Publisher：(一社)日本胆道学会  

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BACKGROUND: This study aimed to investigate the incidence and distribution of regional lymph node metastasis according to tumor location, and to clarify whether tumor location could determine the extent of regional lymphadenectomy in patients with pathological T2 (pT2) gallbladder carcinoma. METHODS: In total, 81 patients with pT2 gallbladder carcinoma (25 with pT2a tumors and 56 with pT2b tumors) who underwent radical resection were enrolled. Tumor location was determined histologically in each gallbladder specimen. RESULTS: Survival after resection was significantly worse in patients with pT2b tumors than those with pT2a tumors (5-year survival, 72% vs. 96%; p = 0.027). Tumor location was an independent prognostic factor on multivariate analysis (hazard ratio, 14.162; p = 0.018). The incidence of regional lymph node metastasis was significantly higher in patients with pT2b tumors than in those with pT2a tumors (46% vs. 20%; p = 0.028). However, the number of positive nodes was similar between the two groups (median, 2 vs. 2; p = 0.910). For node-positive patients with pT2b tumors, metastasis was found in every regional node group (12%-63%), whereas even for node-positive patients with pT2a tumors, metastasis was observed in regional node groups outside the hepatoduodenal ligament. CONCLUSIONS: Tumor location in patients with pT2 gallbladder carcinoma can predict the presence or absence of regional lymph node metastasis but not the number and anatomical distribution of positive regional lymph nodes. The extent of regional lymphadenectomy should not be changed even in patients with pT2a tumors, provided that they are fit enough for surgery.

DOI： 10.1016/j.ejso.2019.03.038

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

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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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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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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A 56-year-old woman was referred to our hospital with complaints of appetite loss and abdominal distension. Enhanced abdominal computed tomography revealed a giant retroperitoneal tumor. We performed en bloc tumor resection. The histological diagnosis was of a dedifferentiated liposarcoma. One year after the initial surgery, 2 tumors were detected around the pancreas using computed tomography. We made a diagnosis of recurrent retroperitoneal liposarcoma and attempted surgical removal of the tumors. However, 1 of the tumors firmly adhered to the pancreas and duodenum; thus, we performed subtotal stomach-preserving pancreaticoduodenectomy to remove the tumors. The histological diagnosis was the same as that obtained during the initial surgery: a dedifferentiated liposarcoma. The patient remains alive and well with no evidence of disease 2 years after the initial surgery.

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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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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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症例は57歳、女性。腹部膨満感と食欲低下を主訴に来院した。腹部CT検査で腹腔内臓器を圧排する巨大な後腹膜腫瘍を認め、後腹膜脂肪肉腫と診断し、手術を施行した。腫瘍は下行結腸、左腎臓、左卵巣を巻き込んでおり、腫瘍とともにこれらの臓器をen blocに摘出した。病理組織学的検査で脱分化型脂肪肉腫と診断された。術後1年目のCT検査で膵頭部背側に低濃度腫瘤の新規出現を認め、脂肪肉腫の再発と診断した。遠隔転移を認めず、完全切除が可能と判断し、再発巣に対して亜全胃温存膵頭十二指腸切除術を施行した。術後は特記すべき合併症を認めなかった。再発巣切除から1年が経過した現在、無再発生存中である。後腹膜脂肪肉腫に対し有効な化学療法が存在しない現況を考慮すると、本疾患の予後改善のためには可能な限り外科的切除を追求する必要があるものと考える。(著者抄録)

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BACKGROUND: Pancreatic cancer is a disease with poor prognosis, and development of new treatments is necessary. Sphingosine-1-phosphate (S1P), a bioactive lipid mediator produced by sphingosine kinases (SphK1 and SphK2), plays a critical role in progression of many types of cancer. However, little is known about the role of sphingosine kinases in pancreatic cancer. This study investigated the roles of sphingosine kinases in pancreatic cancer progression. MATERIALS AND METHODS: S1P levels in pancreatic cancer and noncancerous pancreatic tissue were measured in 10 patients. We generated PAN02 murine pancreatic cancer cell lines with a clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated system genes 9 (Cas9)-mediated deletion of SphK1 or SphK2 and assessed cell growth and migration. In an animal model, we assessed the survival of mice injected with PAN02 cells intraperitoneally. RESULTS: S1P levels in the pancreatic cancer tissue were significantly higher than those in noncancerous tissue. SphK1 knockout (KO) cells showed greater proliferation and migration than wild type (WT) cells, and SphK2 KO cells showed less proliferation and migration than WT cells. Animal experiments showed that the survival of mice injected with SphK1 KO cells was significantly shorter than those injected with WT cells, and the survival of mice injected with SphK2 KO cells was longer than those injected with WT cells. Surprisingly, cytotoxic assay using gemcitabine showed that SphK1 KO cells survived less than WT cells, and SphK2 KO cells survived more than WT cells. CONCLUSIONS: S1P produced by SphK1 and SphK2 may have different functions in pancreatic cancer cells. Targeting both SphK1 and SphK2 may be a potential strategy for pancreatic cancer treatment.

DOI： 10.1016/j.jss.2018.06.019

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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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Other Link： https://search.jamas.or.jp/default/link?pub_year=2018&ichushi_jid=J00296&link_issn=&doc_id=20190107600174&doc_link_id=%2Fab8gtkrc%2F2018%2F004513%2F174%2F2312-2314%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fab8gtkrc%2F2018%2F004513%2F174%2F2312-2314%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

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

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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Other Link： https://search.jamas.or.jp/default/link?pub_year=2018&ichushi_jid=J00296&link_issn=&doc_id=20190107600053&doc_link_id=%2Fab8gtkrc%2F2018%2F004513%2F053%2F1949-1951%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fab8gtkrc%2F2018%2F004513%2F053%2F1949-1951%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Publishing type：Research paper (scientific journal)  

DOI： 10.1111/cas.13904

PubMed

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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：(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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Other Link： https://search.jamas.or.jp/default/link?pub_year=2018&ichushi_jid=J00393&link_issn=&doc_id=20181106040006&doc_link_id=issn%3D0016-593X%26volume%3D80%26issue%3D12%26spage%3D1218&url=http%3A%2F%2Fwww.pieronline.jp%2Fopenurl%3Fissn%3D0016-593X%26volume%3D80%26issue%3D12%26spage%3D1218&type=PierOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00005_2.gif

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

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

Recent advances in dimensional imaging, surgical technique, and perioperative patient care have resulted in increased rates of complete resection with histopathologically negative margins and improved surgical outcomes in patients with extrahepatic cholangiocarcinoma. However, achieving cancer-free resection margins at ductal stumps in surgery for this disease remains challenging because of longitudinal extension, which is one of the hallmarks of extrahepatic cholangiocarcinoma. When the ductal resection margins are shown to be positive on examination of frozen sections, discrimination between carcinoma in situ and invasive carcinoma is clinically important because residual carcinoma in situ may lead to late local recurrence whereas residual invasive carcinoma is associated with early local recurrence. Residual invasive carcinoma at the ductal margins should be avoided whenever technically feasible. Residual "carcinoma in situ" at the ductal margins appears to be allowed in resection for the advanced disease because it has less effect on survival than other adverse prognostic factors (pN1 and/ or pM1). However, in surgery for early-stage (pTis-2N0M0) extrahepatic cholangiocarcinoma, residual carcinoma in situ at the ductal margins may have an adverse effect on long-term survival, so should be avoided whenever possible. In this review, we focus on the histopathological term "carcinoma in situ," the biological behavior of residual carcinoma in situ at ductal resection margins, intraoperative histological examination of the ductal resection margins, outcome of additional resection for positive ductal margins, and adjuvant therapy for patients with positive margins.

DOI： 10.1002/ags3.12196

PubMed

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

BACKGROUND: Neuroendocrine tumors (NETs) of the gallbladder are rare and generally considered low-grade malignancies. We herein describe a case of a patient with a 0.8-cm clear cell NET G1 of the gallbladder with nodal involvement. CASE PRESENTATION: A 65-year-old man with no medical history indicative of von Hippel-Lindau (VHL) disease underwent laparoscopic cholecystectomy for cholecystolithiasis. There was a 0.8-cm tumor in the neck of the gallbladder. Histologic examination revealed nests or trabecular growth of clear cells with small round-to-oval nuclei. Immunohistochemically, tumor cells showed positivity for chromogranin A and synaptophysin; Ki-67 index was < 1.0%. Based on the World Health Organization 2010 classification, we made a diagnosis of clear cell variant of NET G1 without VHL disease. The tumor invaded the muscular layer and had no extension to the perimuscular connective tissue but had metastasized to a cystic duct node. A radical second resection with regional lymphadenectomy of the gallbladder was performed, and there was no metastasis on histology. After the definitive surgery, he was followed up for 10 months without adjuvant therapy and is alive and well with no evidence of recurrence. CONCLUSIONS: Our experience suggests that, even when smaller than 1 cm, NET G1 of the gallbladder can metastasize. When NET G1 is incidentally identified in the gallbladder of a surgical specimen, detailed pathologic examination of the cystic duct node, when found, should be performed to guide whether a radical second resection with regional lymphadenectomy is appropriate.

DOI： 10.1186/s12957-018-1454-y

PubMed

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

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

PubMed

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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：医学図書出版(株)  

胆嚢癌において性差による臨床像の差異を解説するとともに、胆嚢癌の発生と関連する背景疾患や危険因子を性差の観点から概説する。胆嚢癌は女性が占める割合が高い疾患である。本邦の胆嚢癌の全国登録データの解析によると、男性よりも女性で良好な予後(5年全生存率:男性36.8%、女性41.1%、P=0.004)を示すが、本邦では男性より女性の平均寿命が明らかに高齢であることがその一因と考えられている。胆嚢癌のハイリスクである膵・胆管合流異常症は女性が占める割合が高い。女性に多い胆石症と胆嚢癌の発生とに関連する疫学的な報告は多数あるが、現時点では胆石症と胆嚢癌との直接的因果関係は証明されていない。胆嚢癌の発生と女性ホルモンとの関連も示唆されているが、その機序はいまだ明らかではない。性差という疫学的背景を念頭に胆嚢癌の発生と関連する背景疾患や危険因子を理解し、本疾患の早期発見・早期治療につなげることが重要である。(著者抄録)

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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)日本胆道学会  

胆嚢癌の外科治療において良好な長期成績を得るための唯一のコンセンサスは癌遺残のない外科切除(R0切除)である。胆嚢癌は解剖学的特殊性や生物学的悪性度の高さに起因して多様な進展様式をきたすため、R0切除を実施するためには病巣所見に応じて適切に切除範囲を選択していく必要がある。進行胆嚢癌の不良な手術成績を改善するために、本邦を中心に拡大肝右葉切除や膵頭十二指腸切除といった拡大切除術式が提案・実施されてきたが、近年では、その適応と限界が明らかになりつつある。pT2胆嚢癌に対する切除術式に関しては、肝切除範囲、リンパ節郭清範囲、肝外胆管切除の併施の有無のいずれも明確なコンセンサスが得られていない。また、最近では、潜在性胆嚢癌に関する知見も新たに報告されつつある。本稿では胆嚢癌の外科治療の現状を明らかにするとともに、胆嚢癌の病巣所見に応じた至適切除範囲について考察したい。(著者抄録)

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2018&ichushi_jid=J02149&link_issn=&doc_id=20180410230008&doc_link_id=%2Fdw1tando%2F2018%2F003201%2F019%2F0105-0113%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdw1tando%2F2018%2F003201%2F019%2F0105-0113%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：(一社)日本胆道学会  

胆嚢癌について、早期癌、画像診断、肝内進展様式、肝切除範囲、リンパ節郭清範囲を中心に解説する。早期癌に関しては、その概念や肉眼的形態による特徴を十分に理解して診療にあたる必要があり、胆嚢管断端が癌陰性であれば単純胆嚢摘出術で十分であり根治切除は不要である。画像診断では、各種画像の有用性・限界を理解した上で、これらを駆使して胆嚢癌の存在診断を行い、その進行度を評価することが求められる。切除可能な胆嚢癌の主要な肝内進展様式は直接浸潤とグリソン鞘浸潤であり、グリソン鞘浸潤の主体はリンパ管浸潤である。胆嚢癌に対する根治切除の際には、主病巣とその近傍の肝内に潜在する顕微鏡的なグリソン鞘浸潤巣とを除去することに主眼をおいて肝切離マージンを設定する必要がある。#13aリンパ節を含む本邦の胆道癌取扱い規約第6版の定める領域リンパ節が、胆嚢癌における至適なリンパ節郭清範囲である。(著者抄録)

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2018&ichushi_jid=J02149&link_issn=&doc_id=20180410230002&doc_link_id=%2Fdw1tando%2F2018%2F003201%2F003%2F0044-0050%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdw1tando%2F2018%2F003201%2F003%2F0044-0050%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

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

術前診断T2(cT2)の胆嚢癌の治療方針について、自験例の成績と検索した文献から考察した。cT2胆嚢癌に対する肝切除範囲は胆嚢床切除で十分である可能性が高く、腫瘍局在が肝側の腫瘍では胆嚢床切除が原則、必要である。腹腔側の腫瘍では胆嚢床切除が省略できる可能性はあるが、現時点ではその適応は慎重に判断するべきである。少なくとも術中にリンパ節転移陰性と判定されたcT2胆嚢癌に対しては、肝外胆管を温存できることが示唆される。一方で、術中にリンパ節転移陽性と判定した胆嚢癌に対しては、自験例における肝外胆管温存例は胆外胆管切除例よりも郭清リンパ節の評価個数が少なかった結果を考慮して、われわれは肝外胆管切除を併施するほうが望ましいと考えている。cT2胆嚢癌に対するリンパ節郭清範囲は胆道癌取扱い規約第6版が定める領域リンパ節が妥当であり、この範囲をen blocに郭清することが重要である。(著者抄録)

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Publishing type：Research paper (scientific journal)  

Web of Science

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Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.transproceed.2018.03.035

Scopus

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Publishing type：Research paper (scientific journal)  

Web of Science

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Publishing type：Research paper (scientific journal)  

Web of Science

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Language：Japanese   Publisher：(株)医学書院  

＜ポイント＞門脈浸潤を伴う遠位胆管癌は外科切除のみでは長期生存は望めず,borderline resectableとして術前・術後の補助療法を組み合わせた集学的治療で予後の改善を計る必要がある.遠位胆管癌においてR0切除をめざして胆管断端陰性を追求するという治療戦略は妥当であるが,高齢者,高リスクの患者,進行癌患者などに対しては,胆管断端の浸潤癌陰性を追求するが上皮内癌の有無にはこだわらないという柔軟な戦略も許容される.リンパ節転移は強力な予後不良因子であり,術後の病理組織学的検査でリンパ節転移が陽性(特に4個以上)の症例は,術後補助化学療法の良い適応である.(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。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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Other Link： https://search.jamas.or.jp/default/link?pub_year=2017&ichushi_jid=J00296&link_issn=&doc_id=20171221480025&doc_link_id=%2Fab8gtkrc%2F2017%2F004412%2F025%2F1126-1128%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fab8gtkrc%2F2017%2F004412%2F025%2F1126-1128%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

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

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

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

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.

PubMed

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

BACKGROUND: Laparoscopic surgery for patients with portal hypertension is considered to be contraindicated because of the high risk of massive intraoperative hemorrhaging. However, recent reports have shown hand-assisted laparoscopic surgery for devascularization and splenectomy to be a safe and effective method of treating esophagogastric varices with portal hypertension. The aim of this study is to evaluate the efficacy of hand-assisted laparoscopic devascularization and splenectomy (HALS Hassab's procedure) for the treatment of esophagogastric varices with portal hypertension. CASE PRESENTATION: From 2009 to 2016, seven patients with esophagogastric varices with portal hypertension were treated with hand-assisted laparoscopic devascularization and splenectomy in our institute. Four men and three women with a median age of 61 years (range 35-71) were enrolled in this series. We retrospectively reviewed the medical records for the perioperative variables, postoperative mortality and morbidity, and postoperative outcomes of esophagogastric varices. The median operative time was 455 (range 310-671) min. The median intraoperative blood loss was 695 (range 15-2395) ml. The median weight of removed spleen was 507 (range 242-1835) g. The conversion rate to open surgery was 0%. The median postoperative hospital stay was 21 (range 13-81) days. During a median 21 (range 3-43) months of follow-up, the mortality rate was 0%. Four postoperative complications (massive ascites, enteritis, intra-abdominal abscess, and intestinal ulcer) were observed in two patients. Those complications were treated successfully without re-operation. Esophagogastric varices in all patients disappeared or improved. Bleeding from esophagogastric varices was not observed during the follow-up period. CONCLUSION: Although our data are preliminary, hand-assisted laparoscopic devascularization and splenectomy proved an effective procedure for treating esophagogastric varices in patients with portal hypertension.

DOI： 10.1186/s40792-017-0387-y

PubMed

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

BACKGROUND: This study was designed to evaluate the prognostic value of positive posterior superior pancreaticoduodenal lymph nodes to clarify the need for dissection of these nodes. METHODS: A total of 148 patients with gallbladder carcinoma who underwent radical resection including dissection of the posterior superior pancreaticoduodenal nodes were enrolled. The incidence of metastasis and the survival rates among patients with metastasis to each lymph node group were calculated. RESULTS: Of the 148 patients, 70 (47%) had nodal disease. The incidences of metastasis in the cystic duct, pericholedochal, retroportal, and hepatic artery node groups, defined as regional nodes in the UICC TNM staging system, ranged from 8.3 to 24.3% with 5-year survival rates of 12.5-46.4% in patients with positive nodes. The incidence of metastasis to the posterior superior pancreaticoduodenal nodes was 12.8% with a 5-year survival rate of 31.6% in patients with positive nodes. Survival after resection was significantly better in patients with distant nodal disease affecting only the posterior superior pancreaticoduodenal nodes (5-year survival, 55.6%) than in patients with distant nodal disease beyond these nodes (5-year survival, 15.0%; p = 0.046), whereas survival after resection was comparable between the former group and patients with regional nodal disease alone (5-year survival, 40.7%; p = 0.426). CONCLUSIONS: In gallbladder carcinoma, involvement of the posterior superior pancreaticoduodenal nodes is similar to that of regional nodes in terms of both the incidence of metastasis and the impact on survival. Inclusion of the posterior superior pancreaticoduodenal nodes among the regional nodes should be considered.

DOI： 10.1245/s10434-017-5939-7

PubMed

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Language：Japanese   Publisher：(株)アークメディア  

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Language：Japanese   Publisher：(株)南江堂  

進行胆嚢癌に対する外科治療に関して,局所進展度別に至適な肝切除範囲,リンパ節郭清範囲を中心に,現在までに得られている知見を概説した.pT2胆嚢癌に対する至適な肝切除やリンパ節郭清の範囲,肝外胆管切除の必要性に関してはいまだ議論が多い.pT3/pT4胆嚢癌の外科治療成績に関しては,癌遺残のない切除が遂行されれば非切除例よりは良好な成績が得られているが,いまだ十分ではなく,術前・術後の化学療法を含めた集学的治療の進歩が望まれる.進行胆嚢癌に対する外科治療では,癌遺残のない手術を遂行するために個々の症例の病巣所見に応じて適切な根治術式を選択することが重要である.(著者抄録)

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Language：Japanese   Publisher：(一社)日本門脈圧亢進症学会  

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Language：Japanese   Publisher：(一社)日本門脈圧亢進症学会  

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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)医学書院  

＜ポイント＞領域リンパ節郭清の際には,温存すべき脈管や膵頭部といった正常組織を露出する層で剥離を進め,リンパ節を含む残りの組織をすべてen blocに摘出する意識が大切である.胆嚢床切除を行う際には,胆嚢板に近づかないように肝切離を進めて肝前区域のグリソン鞘本幹に到達し,胆嚢板をグリソン鞘への移行部で切離する.胆管を温存して胆管周囲のリンパ節を郭清する際には,右肝動脈および後上膵十二指腸動脈から分岐するいわゆる3 o'clock artery・9 o'clock artery,および胆管の血管網を温存する層で剥離を進める.(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：Japanese   Publisher：(一社)日本消化器外科学会  

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DOI： 10.1093/geroni/igx005

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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DOI： 10.1016/j.ejso.2017.01.001

Scopus

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：E-CENTURY PUBLISHING CORP  

NAD(P)H: quinone oxidoreductase-1 (NQO1) protects cells against redox cycling and oxidative stress; however, in cancer cells, NQO1 confers resistance against anticancer agents. The aim of this study was to evaluate the association between NQO1 expression and prognosis in patients with advanced (locally advanced or metastatic/recurrent) colorectal cancer (CRC). A retrospective analysis of 47 patients [28 male and 19 female; median age: 62 years (range, 17-78)] with advanced CRC was conducted. Immunohistochemical examination of tumor tissue specimens was performed using monoclonal anti-NQO1 antibody. The association of NQO1 expression with patient characteristics, chemotherapeutic response, and clinical prognosis was assessed. Therapeutic efficacy (complete response, partial response, stable disease, and progressive disease) was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. We compared the therapeutic efficacy in KRAS wild and mutant CRC because epidermal growth factor receptor (EGFR)-signaling pathway plays a pivotal role in CRC. Of the 47 patients, 31 (66.0%) had KRAS wild CRC and 16 (34.0%) had KRAS mutant CRC. Moreover, 37 (78.7%) had NQO1-positive tumors and 10 (21.3%) had NQO1-negative tumors. Among the patients with KRAS wild CRC, NQO1-negative patients showed significantly better disease control rate (complete response + partial response + stable disease) than NQO1-positive patients (P = 0.028). Moreover, NQO1-negative patients had longer progression-free survival and overall survival than NQO1-positive patients (P = 0.041 and P = 0.043, respectively). NQO1 expression in the tumor may be a predictor of therapeutic efficacy and prognosis in patients with KRAS wild advanced CRC.

Web of Science

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

A 64-year-old woman diagnosed with duodenal adenocarcinoma with duodenal stenosis and obstructive jaundice was referred to our hospital. Computed tomography revealed a tumor measuring 9×6 cm in the second portion of the duodenum that had invaded the liver(S6)and head of the pancreas. After percutaneous transhepatic biliary drainage for obstructive jaundice, the patient underwent subtotal stomach-preserving pancreaticoduodenectomy, partial resection of the liver(S6), and partial resection of the colon. Histologic examination showed the primary tumor to be moderately and poorly differentiated adenocarcinoma with hepatic and pancreatic invasion; lymph node metastasis was not found. The patient received S-1 for 1 year and remains alive and well with no evidence of disease 15 months after resection.

PubMed

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

A 66-year-old woman with pancreatic cancer underwent resection of the pancreatic body and tail. Thirty-seven months after the initial surgery, a tumor was found in S4 of the right lung, for which resection of the middle lobe of the lung was performed. A diagnosis of lung metastasis originating from pancreatic cancer was confirmed based on histological and immunohistopathological assessments. Sixty-seven months after the initial surgery, despite the gemcitabine-based adjuvant chemotherapy, a tumor was detected in S3 of the left lung, for which partial lung resection was performed. Similar to the previous diagnosis, the tumor was diagnosed as lung metastasis of pancreatic cancer on the basis of the pathological findings. After the third operation, despite gemcitabine and S-1 chemotherapy, widespread pulmonary metastasis developed. One hundred and thirty months after the initial surgery, the patient died of respiratory failure due to carcinomatous pleurisy.

PubMed

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A 77-year-old woman with rectal cancer and synchronous liver metastasis underwent a Hartmann operation with D3 lymph node dissection in June 2014. mFOLFOX6 plus bevacizumab(bev)was then administered to treat the liver metastasis.In February 2015, multiple liver metastases were detected and the regimen was changed to FOLFIRI plus bev.After 3 courses, peritonitis due to intestinal perforation around the descending colostomy occurred, and an emergency operation(partial resection of the descending colon and transverse colostomy)was performed.FOLFIRI was then administered from 2 months after the operation.After 3 courses of this regimen, a CT scan showed progression of the hepatic metastases.The regimen was therefore changed to mFOLFOX6.Five months later, another CT scan showed an intestinal perforation of the transverse colostomy at the abdominal wall, and an emergency cecostomy was performed.At this stage, chemotherapy was ceased.This case highlights the risk of intestinal perforation during chemotherapy, regardless of the use of bev.

PubMed

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

A 77-year-old woman presented with a high fever. She had a history of resection of the extrahepatic bile duct, cholecystectomy, and hepaticojejunostomy for a congenital choledochal cyst, 23 years previously. Computed tomography showed a tumor measuring 90mm behind the head of the pancreas. This tumor appeared to invade the duodenum and pancreas, although swollen lymph nodes and distant metastasis were not detected. The patient was diagnosed with a carcinoma arising from the intrapancreatic remnant bile duct. A subtotal stomach-preserving pancreaticoduodenectomy and regional lymphadenectomy were performed. The patient remains alive and well with no evidence of disease 11 months after resection.

PubMed

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A 78-year-old man with jaundice was diagnosed with perihilar cholangiocarcinoma(Bismuth type I ). After endoscopic biliary drainage for jaundice, a subtotal stomach-preserving pancreaticoduodenectomy was performed. Histologic examination and immunohistochemical staining with chromogranin A, synaptophysin, and CD56 resulted in a diagnosis of small cell carcinoma. Of the 18 dissected lymph nodes, 8 nodes contained a metastatic tumor. Left supraclavicular and paraaortic lymph node metastases were detected by computed tomography 5 months after the resection. He received cisplatin plus irinotecan chemotherapy, and after 2 courses of the chemotherapy, both metastatic lesions were reduced in size. He remains alive and well with no evidence of progressive disease after 6 courses of chemotherapy.

PubMed

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

症例は68歳、女性。66歳時に膵体部癌に対し膵体尾部切除術とゲムシタビン(GEM)による補助化学療法を施行した。術後37ヵ月目のCT検査で右肺S4に8mm大の孤立性腫瘤を認めた。他臓器に明らかな再発所見を認めず、右肺中葉切除術を施行した。病理組織像は原発巣と類似し、免疫組織化学の所見と合わせ、膵癌の肺転移と診断した。肺切除後にGEM単剤療法を再開したが、初回手術後67ヵ月目のCT検査にて左肺S3に孤立性腫瘤を認め、再々発を疑い左肺部分切除術を施行した。前回と同様な組織像で、膵癌の肺転移であった。術後にS-1単剤療法を行ったが、初回手術後110ヵ月目に肺再発と癌性胸膜炎を認めた。GEM+S-1併用療法を行ったが、初回手術後130ヵ月目に原病死した。膵癌術後の孤立性肺転移においては、積極的な外科切除と化学療法による集学的治療が予後を改善する症例も存在する。(著者抄録)

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

症例は77歳、女性。先天性胆道拡張症に対して23年前に肝外胆管切除、胆嚢摘出、肝管空腸吻合からなる分流手術が実施された。今回発熱で発症し、腹部CT検査で膵頭部背側に径90mm大の腫瘤を認め、膵内遺残胆管癌と診断された。膵・十二指腸への直接浸潤がみられたが、明らかなリンパ節転移や遠隔転移を認めなかった。根治切除として亜全胃温存膵頭十二指腸切除、領域リンパ節郭清を施行した。術後11ヵ月が経過した現在、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78歳、男性。黄疸で発症し、精査で領域リンパ節転移を伴う肝門部胆管癌(Bismuth I型)と診断された。内視鏡的経鼻胆道ドレナージで減黄後に、亜全胃温存膵頭十二指腸切除術が施行された。原発巣の免疫組織化学はchromogranin A、synaptophysin、CD56のすべてが陽性で、病理組織学的に胆管小細胞癌と診断された。胆管断端は陰性であったが、領域リンパ節8個が転移陽性であった。術後5ヵ月目の腹部CT検査で、左鎖骨上・腹部大動脈周囲リンパ節に再発を認めた。cisplatin(CDDP)/irinotecan(CPT-11)療法を2コース施行し、治療効果判定は部分奏効(PR)であった。CDDP/CPT-11療法を計6コース施行後の現在、縮小した再発巣の再増大や新規病変の出現はみられていない。胆管小細胞癌の術後リンパ節再発に対してCDDP/CPT-11療法は考慮すべき治療選択肢の一つと考えられる。(著者抄録)

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症例は64歳、女性。消化管通過障害と閉塞性黄疸を伴う十二指腸癌の診断で当科を紹介受診した。精査の結果、十二指腸下行脚を中心に9×6cm大の腫瘤を認め、腫瘤は肝S6・膵頭部へ直接浸潤していた。リンパ節転移が疑われたが、明らかな遠隔転移を認めなかった。経皮経肝胆道ドレナージによる減黄後、亜全胃温存膵頭十二指腸切除、肝部分切除、結腸部分切除(結腸間膜浸潤陽性)、リンパ節郭清、Child変法再建を施行した。病理組織学的検査の結果は、肝・膵直接浸潤を伴う中分化型から低分化型の管状腺癌であり、リンパ節転移は認めなかった。術後化学療法としてS-1隔日投与を1年間継続し、術後1年3ヵ月が経過した現在、無再発生存中である。(著者抄録)

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

An 82-year-old man with upper abdominal pain was referred to our hospital because of an elevated serum CEA level and dilatation of the intrahepatic bile ducts on ultrasonography.Computed tomography revealed a hypovascular mass measuring 5.0 cm in size in the lateral section, dilatation of the peripheral intrahepatic bile ducts, and swollen lymph nodes around the lesser curvature of the stomach, the common hepatic artery, and the paraaorta.He was diagnosed with unresectable intrahepatic cholangiocarcinoma, and he received chemotherapy with biweekly gemcitabine plus cisplatin.After 33 courses of the chemotherapy, computed tomography revealed that the tumor size decreased over 63%, and all swollen lymph nodes had almost resolved.He underwent a left hemihepatectomy 1 year 6 months after the start of the chemotherapy.He remains alive and well with no evidence of recurrence, 11 months after resection.

PubMed

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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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Patients with unresectable hepatocellular carcinoma (HCC) cannot generally be cured by systemic chemotherapy or radiotherapy due to their poor response to conventional therapeutic agents. The development of novel and efficient targeted therapies to increase their treatment options depends on the elucidation of the molecular mechanisms that underlie the pathogenesis of HCC. The DNA damage response (DDR) is a network of cell-signaling events that are triggered by DNA damage. Its dysregulation is thought to be one of the key mechanisms underlying the generation of HCC. Sphingosine-1-phosphate (S1P), a lipid mediator, has emerged as an important signaling molecule that has been found to be involved in many cellular functions. In the liver, the alteration of S1P signaling potentially affects the DDR pathways. In this review, we explore the role of the DDR in hepatocarcinogenesis of various etiologies, including hepatitis B and C infection and non-alcoholic steatohepatitis. Furthermore, we discuss the metabolism and functions of S1P that may affect the hepatic DDR. The elucidation of the pathogenic role of S1P may create new avenues of research into therapeutic strategies for patients with HCC.

DOI： 10.1007/s00595-015-1270-8

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Based on research carried out over the last decade, it has become increasingly evident that bile acids act not only as detergents, but also as important signaling molecules that exert various biological effects via activation of specific nuclear receptors and cell signaling pathways. Bile acids also regulate the expression of numerous genes encoding enzymes and proteins involved in the synthesis and metabolism of bile acids, glucose, fatty acids, and lipoproteins, as well as energy metabolism. Receptors activated by bile acids include, farnesoid X receptor α, pregnane X receptor, vitamin D receptor, and G protein-coupled receptors, TGR5, muscarinic receptor 2, and sphingosine-1-phosphate receptor (S1PR)2. The ligand of S1PR2, sphingosine-1-phosphate (S1P), is a bioactive lipid mediator that regulates various physiological and pathophysiological cellular processes. We have recently reported that conjugated bile acids, via S1PR2, activate and upregulate nuclear sphingosine kinase 2, increase nuclear S1P, and induce genes encoding enzymes and transporters involved in lipid and sterol metabolism in the liver. Here, we discuss the role of bile acids and S1P signaling in the regulation of hepatic lipid metabolism and in hepatobiliary diseases.

DOI： 10.1194/jlr.R069286

PubMed

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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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p62/Sqstm1 is a multifunctional protein involved in cell survival, growth and death, that is degraded by autophagy. Amplification of the p62/Sqstm1 gene, and aberrant accumulation and phosphorylation of p62/Sqstm1, have been implicated in tumour development. Herein, we reveal the molecular mechanism of p62/Sqstm1-dependent malignant progression, and suggest that molecular targeting of p62/Sqstm1 represents a potential chemotherapeutic approach against hepatocellular carcinoma (HCC). Phosphorylation of p62/Sqstm1 at Ser349 directs glucose to the glucuronate pathway, and glutamine towards glutathione synthesis through activation of the transcription factor Nrf2. These changes provide HCC cells with tolerance to anti-cancer drugs and proliferation potency. Phosphorylated p62/Sqstm1 accumulates in tumour regions positive for hepatitis C virus (HCV). An inhibitor of phosphorylated p62-dependent Nrf2 activation suppresses the proliferation and anticancer agent tolerance of HCC. Our data indicate that this Nrf2 inhibitor could be used to make cancer cells less resistant to anticancer drugs, especially in HCV-positive HCC patients.

DOI： 10.1038/ncomms12030

PubMed

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Language：Japanese   Publisher：(一社)日本肝胆膵外科学会  

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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)南江堂  

肝内胆管癌の肉眼型分類は腫瘍の進展様式を反映し,手術成績に影響を与える.胆管浸潤型はGlisson鞘に沿った進展を特徴とし,高率にリンパ節転移を伴い,根治切除として拡大肝葉切除+肝外胆管切除+リンパ節郭清が施行されても予後不良な場合が少なくない.一方,胆管内発育型は周囲組織への浸潤傾向がとぼしく,リンパ節転移の頻度も低いため良好な予後が期待される.いずれの肉眼型においても長期生存を得るためにはR0切除が必須であるが,拡大手術は高率に合併症を伴うため,過不足のない適切な術式選択が求められる.(著者抄録)

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BACKGROUND: This study aimed to compare the utility of the number of positive lymph nodes with the lymph node ratio (LNR) in predicting survival after resection of extrahepatic cholangiocarcinoma. METHODS: A retrospective analysis of 142 consecutive patients who underwent radical resection of extrahepatic cholangiocarcinoma was performed. A total of 3066 regional lymph nodes were resected. The median number of nodes per patient was 21. The optimal cutoff values for the number of positive nodes and the LNR were determined using the Chi square scores calculated by the Cox proportional hazards regression model. RESULTS: Nodal disease was found in 59 patients (42 %). In the subsequent analysis of the impact that nodal status has on survival, 18 patients with R1/2 resection and 6 patients with paraaortic nodal disease who did not survive for more than 5 years after resection were excluded. The optimal cutoff value for the number of positive nodes was 1, and the optimal cutoff value for the LNR was 5 %. Univariate analysis identified both the number of positive nodes (0, 1, or ≥2; P = 0.005) and the LNR (0, 0-5, or >5 %; P = 0.007) as significant prognostic factors. Multivariate analysis identified the number of positive nodes but not the LNR as an independent prognostic factor (P = 0.012). The 5-year survival rates were 64 % for the patients with no positive nodes, 46 % for the patients with one positive node, and 28 % for the patients with two or more positive nodes. CONCLUSIONS: The number of positive lymph nodes predicts survival better than the LNR after resection of extrahepatic cholangiocarcinoma, provided that nodal evaluation is sufficient.

DOI： 10.1245/s10434-015-4609-x

PubMed

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DOI： 10.1038/HR.2016.60

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DOI： 10.1016/j.transproceed.2015.12.113

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DOI： 10.1016/j.transproceed.2016.01.026

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DOI： 10.1016/j.transproceed.2016.01.030

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DOI： 10.1016/j.transproceed.2015.12.093

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

A 62-year-old man presented with pruritus caused by obstructive jaundice. He was diagnosed with carcinoma of the ampulla of Vater and underwent pylorus-preserving pancreaticoduodenectomy. Histologic examination revealed signet-ring cell carcinoma without nodal metastasis. The patient underwent a partial resection of the small bowel for small bowel obstruction 38 months after the initial resection. Histologic examination disclosed signet-ring cell carcinoma at the surface of the resected small bowel, and the diagnosis of peritoneal recurrence was confirmed. He received oral S-1(100 mg/day) every other day for 14 months until bowel obstruction caused by peritoneal carcinomatosis became apparent. The patient died of the disease 58 months after the initial resection.

PubMed

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

症例は51歳、男性。右腎淡明細胞癌に対して右腎摘出術を施行した。術後6ヵ月目に膵尾部に単発の転移巣を認め、尾側膵切除術、脾摘出術を施行した。初回手術から1年6ヵ月目に膵頭部に単発の転移巣を認め、腫瘍の核出術を施行した。さらに、初回手術から3年10ヵ月目の今回、残膵体部に転移巣を認め、膵頭部を温存して残膵の尾側膵切除術を施行した。初回手術から4年が経過し、癌遺残なく生存中である。(著者抄録)

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

症例は46歳、女性。混合型肝癌に対し肝右葉切除術、胆嚢摘出術、肝門部リンパ節のサンプリングを施行した。術後にS-1内服を開始したが、血清CEA値は経時的に漸増した。術後12ヵ月目のPET-CT検査で孤立性の大動脈周囲リンパ節再発と診断され、大動脈周囲リンパ節郭清を施行した。組織学的にリンパ節再発巣は肝細胞癌成分で構成されていた。術後にソラフェニブ内服を開始した。肝切除後17ヵ月が経過し、生存中である。混合型肝癌の孤立性大動脈周囲リンパ節転移再発に対しては、特にリンパ節転移個数が少数であれば外科切除を含む集学的治療により予後改善が期待される。(著者抄録)

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

A 54-year-old female patient was admitted with obstructive jaundice. The patient was diagnosed with locally advanced unresectable pancreatic cancer of the head with invasion to the super mesenteric artery and the third portion of the duodenum. A biliary- and gastric-enteric bypass surgery was performed, and peritoneal lavage cytology was positive during surgery. After 6 courses of gemcitabine and S-1 combination chemotherapy, the CA19-9 level was normalized and the primary tumor shrank to 79% of its original size. Diagnostic laparoscopy revealed that distant metastasis was not detected and the peritoneal lavage cytology was negative. After additional chemoradiation therapy, a pancreaticoduodenectomy was perfomed. Microscopic investigation revealed that about 60% of the cancer tissue had been replaced by fibrosis and no cancer cells were found at the surgical margin. The patient was alive with no evidence of recurrence 17 months after radical surgery.

PubMed

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

A 51-year-old man underwent right nephrectomy for renal cell carcinoma. Six months later, a solitary metastatic tumor was detected in the pancreatic tail and he underwent distal pancreatectomy and splenectomy. One year and 6 months after the initial resection, a solitary metastatic tumor was detected in the pancreas head, and he underwent partial pancreatectomy. A solitary metastatic tumor was detected again in the remnant pancreatic body 3 years and 10 months after the initial resection. Partial resection of the distal part of the remnant pancreas was performed. The patient remains alive and well with no evidence of remnant disease 4 years after the initial resection.

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Language：Japanese   Publisher：新潟医学会  

症例は80歳女性. 前医で下部直腸癌に対し経肛門的局所切除術が施行された. 局所切除後2年1か月目に, 外陰部から肛門にかけて掻痒を伴う紅色扁平隆起性病変が明らかとなった. 生検でPaget細胞が認められた. 乳房外Paget病は, 皮膚原発の一次性乳房外Paget病と二次性乳房外Paget病に分類され, 鑑別診断には免疫組織化学染色が有用である. 本症例では, 免疫組織化学染色でGCDFP-15陰性, CK20陽性, CK7陰性であり, Pagetoid spreadを伴う直腸癌局所再発と診断した. CT検査で所属リンパ節および遠隔転移を認めなかった. 外陰部膣合併切除を伴う腹会陰式直腸切断術を行うことで, 治癒切除となった. 直腸癌局所切除後のPagetoid spreadを伴う再発形式は稀であるが, Paget細胞遺残の可能性を考慮し, 外来通院時の肛門皮膚観察に注意すべきである.

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

A 46-year-old woman underwent right hemihepatectomy, cholecystectomy, and sampling of the hilar lymph nodes for combined hepatocellular and cholangiocarcinoma. She received oral S-1 after hepatectomy. However, her serum level of carcinoembryonic antigen gradually increased, and solitary paraaortic lymph node recurrence was detected on positron emission tomography-computed tomography 12 months after hepatectomy. The patient underwent paraaortic lymph node dissection. Histologic examination revealed solitary paraaortic lymph node metastasis composed of hepatocellular carcinoma. After paraaortic lymph node dissection, she was administered sorafenib, and she remains alive and healthy with no evidence of disease 17 months after the initial resection.

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Language：Japanese   Publisher：新潟医学会  

【緒言】UICC/AJCC TNM分類第7版において、肝外胆管癌は肝門部領域胆管癌と遠位胆管癌とに分類された。本邦の胆道癌取扱い規約第6版においてもTNM分類に準拠して、肝内腫瘤の有無にかかわらず、肝側左側は門脈臍部の右縁から肝側右側は門脈前後枝の分岐点の左縁までの範囲である肝門部領域胆管に主座のある癌を肝門部領域胆管癌と定義している。肝門部領域胆管癌は、肝内直接浸潤陽性肝門部胆管癌と肝門部浸潤陽性肝内胆管癌とが含まれているが、両者を臨床的に鑑別することは困難であることがある。本研究の目的は、肝内直接浸潤陽性肝門部胆管癌と肝門部浸潤陽性肝内胆管癌とを肝門部領域胆管癌として扱い、血管胆管鞘への組織学的腫瘍浸潤に基づく進展様式を評価することで両者を鑑別することが可能であるかを検証することである。【材料と方法】1988年1月から2011年12月までに当科で根治切除が行われた胆管癌164例中、組織学的に肝門部浸潤およびpHinf1b以上の肝内直接浸潤の両者を認めた肝門部領域胆管癌52例を対象とした。本研究では、hematoxylin-eosin and Victoria Blue(HE-VB)二重染色にて血管胆管鞘(Glisson鞘、Laennec被膜、肝門板)の弾性線維を同定し、血管胆管鞘への組織学的腫瘍浸潤に基づく進展様式を評価することで原発部位を判定し、肝内直接浸潤陽性肝門部胆管癌と肝門部浸潤陽性肝内胆管癌とを鑑別した。【結果】術式は、全例において胆道再建を伴う肝葉切除以上の肝切除が施行されていた。HE-VB二重染色による組織所見において血管胆管鞘の弾性線維は、肝内と肝外とを隔てている解剖学的判断基準であり、腫瘍浸潤部位でも弾性線維の構造は保たれていた。このため、HE-VB二重染色により同定された血管胆管鞘の弾性線維を判断基準とし、肝外から肝内へ浸潤する肝内直接浸潤陽性肝門部胆管癌と、肝内から肝外へ浸潤する肝門部浸潤陽性肝内胆管癌とを組織学的に鑑別することは可能であった。組織学的に大型胆管から肝内へ浸潤する腫瘍のうち、腫瘍の主座が胆管二次分枝あるいは胆管二次分枝より末梢に存在する場合は、規約に準拠し、肝門部浸潤陽性肝内胆管癌とした。この組織学的分類の結果、肝内直接浸潤陽性肝門部胆管癌34例、肝門部浸潤陽性肝内胆管癌18例であった。肝門部浸潤陽性肝内胆管癌は肝内直接浸潤陽性肝門部胆管癌と比較して有意に無黄疸例が多く(P<0.001)、血管浸潤(P=0.006)、組織学的遠隔転移(P=0.003)、遺残腫瘍(P=0.040)の陽性頻度が有意に高かった。【結語】肝門部領域胆管癌において、HE-VB二重染色を用いて同定された血管胆管鞘の弾性線維への組織学的腫瘍浸潤に基づく進展様式を評価することで、肝内直接浸潤陽性肝門部胆管癌と肝門部浸潤陽性肝内胆管癌とを鑑別することが可能である。(著者抄録)

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

症例は62歳、男性。閉塞性黄疸に伴う全身そう痒感を主訴に当院を受診した。精査の結果、十二指腸乳頭部癌の診断となり、幽門輪温存膵頭十二指腸切除術を施行された。病理組織学的検査で印環細胞癌と診断された。リンパ節転移は認められなかった。術後補助化学療法を施行せず経過観察されていたが、術後38ヵ月目にイレウスを発症し、癒着剥離術、回腸部分切除術を施行された。病理組織学的検査では切除回腸の狭窄部に印環細胞癌を認め、腹膜播種再発と診断された。化学療法としてS-1隔日投与を開始し、14ヵ月間、腹膜播種増悪によるイレウスを発症するまで継続した。術後58ヵ月で原病死となった。(著者抄録)

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

症例は54歳、女性。閉塞性黄疸で発症し、上腸間膜動脈(SMA)浸潤および十二指腸狭窄を伴う局所進行切除不能膵頭部癌と診断された。胆道および消化管バイパス術を施行したが、開腹所見では腹膜播種は認めないものの、腹腔内洗浄細胞診(CY)は陽性であった。術後にgemcitabineおよびS-1による化学療法を6コース施行した。SMA周囲の軟部影は若干縮小したが残存し、CTでのRECISTによる効果判定はSDであった。adjuvant surgeryの適応を判断するため、審査腹腔鏡を施行した。遠隔転移は認めず、CYは陰性であった。化学放射線療法を追加した後に膵頭十二指腸切除術を行った。病理所見では腫瘍部の約60%は線維化組織に置き換わり、SMA周囲神経叢浸潤は認めなかった。根治術後17ヵ月経過し、無再発生存中である。切除不能膵癌であっても、化学療法が奏効した場合は切除へのconversionが可能となることがある。(著者抄録)

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

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Pneumatosis cystoides intestinalis (PCI) is a relatively rare condition, characterized by subserosal or submucosal air within the bowel wall. Herein, we report a rare case of PCI secondary to treatment with an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). A 71-year-old man, who had received gefitinib therapy for 2 years and 5 months for lung adenocarcinoma with metastases to the bones and brain, presented with abdominal pain, diarrhea, and vomiting. Computed tomography of the abdomen revealed intramural air in the small bowel, free air in the abdomen, and moderate ascites. A diagnosis of PCI was made, and the patient was managed conservatively by discontinuing gefitinib treatment, because his vital signs were stable and there was no sign of peritonitis. The patient's symptoms gradually improved, and follow-up CT after 1 week revealed that the initial findings had almost completely resolved. Clinicians should note that treatment with gefitinib might cause PCI.

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症例は71歳、男性。骨転移、脳転移を伴う肺腺癌に対して、2年5ヵ月前よりgefitinib(250mg/日)を連日投与され、安定(stable disease:SD)を維持中に腹痛、下痢、嘔吐を発症した。腹部骨盤造影CT検査を施行すると小腸壁内ガス像、腹腔内遊離ガス像、中等量の腹水を認め、腸管嚢腫様気腫症(pneumatosis cystoides intestinalis:PCI)の診断となった。バイタルサインが安定し、腹部理学所見で腹膜炎を疑う所見がみられなかったため、gefitinibを休薬して保存的に治療を開始した。自覚症状は徐々に改善し、治療開始7日後の腹部骨盤造影CT検査では画像所見も著明に改善した。(著者抄録)

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Language：Japanese   Publisher：(一社)日本肝胆膵外科学会  

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

症例は29歳,男性。車同士の交通外傷で受傷し当院へ救急搬送された。下腹部にシートベルト痕を認め,全身CTで下顎骨,右鎖骨,左第10肋骨,右腓骨の多発骨折および腹腔内出血を認めた。消化管穿孔は明らかではなかったが,確定診断のため腹腔鏡手術の適応とした。S状結腸腸間膜損傷IIa(S)およびS状結腸損傷cIa(S)の診断でS状結腸切除術を施行した。しかし,術後腸閉塞となったため初回手術後8日目に腹部CTを施行した。腹部正中臍下部で小腸が皮下に脱出しており外傷性腹壁ヘルニア嵌頓と診断した。再手術とし開腹すると,ポートサイトではなく弓状線尾側の下腹部で腹直筋鞘が断裂していた。小腸部分切除を施行し,腹直筋鞘を直接縫合した。今後,腹部鈍的外傷において,診断を兼ねた腹腔鏡手術例は増えてくると思われる。外傷性腹壁ヘルニアは,まれな病態ではあるが,腹腔鏡手術にて見落としがちな腹壁の損傷には注意すべきである。(著者抄録)

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BACKGROUND: The aims of this study were to identify prognostic factors of patients with submucosa-invasive (T1b) gastric cancer and to verify the validity of adjuvant chemotherapy for this disease. METHODS: We retrospectively examined the cases of 1,236 consecutive patients in our prospectively maintained database with T1b gastric cancer who underwent gastrectomy in 1995-2012. We used 11 clinicopathologic characteristics to identify prognostic factors by univariate and multivariate analyses. We compared the survival of the 160 node-positive T1b gastric cancer patients with that of 133 patients in the same database who had node-positive muscularis propria-invasive (T2) gastric cancer and had undergone gastrectomy without adjuvant chemotherapy during the same period, as a reference cohort. RESULTS: The 5-year overall survival rate was 91.4% for all 1,236 patients. Advanced age (hazard ratio [HR] 4.51; 95% confidence interval [CI] 3.26-6.24; P < .01), male sex (HR 2.26; 95% CI 1.56-3.26; P < .01), and the presence of lymph node metastasis (HR 1.89; 95% CI 1.33-2.70; P < .01) were independent prognostic factors. The 5-year overall survival rates were 92.5% in node-negative patients, 84.5% in patients with 1 or 2 metastatic nodes, and 80.1% in patients with 3 or more metastatic nodes (P < .01). The 5-year overall survival rates of the node-positive T1b and T2 gastric cancer patients were 83.6% and 81.2%, respectively (P = .73). CONCLUSION: The prognosis of node-positive T1b gastric cancer patients after curative gastrectomy was unsatisfactory. Adjuvant chemotherapy should be considered for these patients, especially those with 3 or more metastatic nodes.

DOI： 10.1016/j.surg.2014.10.009

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：新潟医学会  

【目的】手術部位感染(SSI)の発生率、術前胆汁培養検査の陽性率、経皮経肝胆道ドレナージ(PTBD)瘻孔部播種の発生率の観点から、肝外胆管癌における術前胆道ドレナージ法としてPTBDと内視鏡的胆道ドレナージ(EBD)のどちらが優れているかを明らかにする。【対象と方法】EBDが導入普及してきた2001年1月以降、2011年7月までの間に、術前胆道ドレナージ施行後に当科で根治切除を施行された肝外胆管癌68例を対象とした。PTBDが32例、EBDが36例で施行された。68例中63例で術前胆汁培養検査が実施された。【結果】PTBD施行群、EBD施行群のSSI発生率は、各々59%(19/32例)、61%(22/36例)であり、両群で有意な差を認めなかった(P>0.999)。術前胆汁培養検査が実施された63例中48例(76%)で合計23種類の細菌が検出された。Streptococcus属が最多で、次いで、Staphylococcus属、Klebsiella属、Enterococcus属の順であった。術前胆汁培養検査陽性でSSIを発症した28例中15例(54%)で、術前胆汁とSSI発生部位の両者で少なくとも1種類の共通の細菌が検出された。PTBD施行群31例中22例(71%)、EBD施行群32例中26例(81%)で術前胆汁培養検査が陽性であった(P=0.387)。EBD施行群ではPTBD施行群と比較して、口腔内や上部消化管常在のStreptococcus属の検出頻度が高かった(P=0.003)。PTBD施行群32例中2例(6%)でPTBDの瘻孔部播種を認めた。いずれの症例も播種巣と原発巣とを同時に切除したが早期に再発をきたした。【結論】肝外胆管癌において、SSIの発生率や術前胆汁細菌培養検査の陽性率の観点からは、PTBD施行群とEBD施行群とで術前胆道ドレナージ法としての優劣は認められなかった。一方、PTBDの瘻孔部播種の発生は決してまれではなく、腫瘍学的な観点からは、肝外胆管癌に対する術前胆道ドレナージ法はEBDの方が優れている。(著者抄録)

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

当科における局所進展度pT2以上の胆嚢癌145例のリンパ節転移からみた手術成績を呈示し、胆嚢癌の至適リンパ節郭清範囲について概説した。145例のリンパ節郭清範囲は、領域リンパ節が116例、領域リンパ節+膵頭周囲リンパ節(膵頭十二指腸切除併施)が29例であった。癌遺残の無いR0手術が実施された123例で解析すると、リンパ節転移陰性57例、リンパ節転移陽性66例の5年生存率は、おのおの75%、43%であった(P<0.001)。リンパ節転移陽性で5年生存したのは24例で、そのうちリンパ節転移個数が4個以上であった4例中3例で膵頭周囲リンパ節転移に対して膵頭十二指腸切除が併施されていた。胆嚢癌の至適リンパ節郭清範囲は領域リンパ節であり、領域リンパ節郭清によりリンパ節転移陽性の長期生存例を得ることができ、胆嚢癌の手術成績は向上する。膵頭十二指腸切除は膵頭周囲リンパ節転移陽性例の予後を改善する可能性がある。(著者抄録)

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Web of Science

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Web of Science

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

症例は81歳、男性。主訴は腹痛、嘔吐で腸閉塞を生じ、近医で入院加療が行われた。保存的治療で症状は改善したが、2ヵ月後に同じ症状で再入院となった。腹部骨盤部CT検査で小腸壁の肥厚が指摘されたため、当院紹介となった。小腸内視鏡検査で空腸に亜全周性の隆起性腫瘍を認め、生検で高分化〜中分化腺癌と診断された。狭窄所見を伴う空腸癌と診断し、単孔式腹腔鏡補助下空腸部分切除術を行った。術中所見として、空腸に炎症性変化を伴う腫瘍が確認された。リンパ節の腫大を認めたため腸管周囲リンパ節の郭清を行った。病理組織結果は小腸中分化管状腺癌、リンパ節は2/5個で転移陽性であった。術後経過は良好で、7病日に退院となった。術後補助化学療法は希望されなかった。術後すぐに日常生活動作は回復し、自宅で生活されていた。術後1年6ヵ月ごろより腹膜再発による腹部膨満を生じ、1年7ヵ月で永眠された。(著者抄録)

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An 81-year-old man presented with chief complaints of abdominal pain and vomiting. Intestinal obstruction was found at the time of admission to a local hospital in October 2011. Conservative treatment provided symptomatic relief; however, he was readmitted with similar symptoms in December 2011. Small-intestinal wall thickening was detected by abdominal and pelvic computed tomography, and he was referred to our hospital. Small-bowel endoscopy revealed an elevated subcircumferential tumor in the jejunum. Biopsy revealed well to moderately differentiated adenocarcinoma diagnosed as jejunal cancer, which caused narrowing of the jejunum. Single-incision laparoscopy-assisted small-bowel resection was performed. The intraoperative findings were a tumor with inflammatory changes in the jejunum and enlarged surrounding lymph nodes. We performed regional lymph node dissection. Histopathological analysis showed moderately differentiated small-intestinal tubular adenocarcinoma and 2 of 5 lymph nodes positive for metastatic cancer cells. After an uneventful postoperative course, he was discharged on day 7. He preferred not to undergo postoperative adjuvant chemotherapy and quickly recovered his activities of daily living postoperatively. He stayed home until he developed abdominal distention resulting from peritoneal recurrence 1 year and 6 months postoperatively and died 1 month later.

PubMed

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Language：Japanese   Publisher：新潟医学会  

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

早期胆嚢癌317例を用いて、その肉眼的・組織学的特徴を検討した。肉眼型別頻度は、隆起型が37.2%(118例)で、表面型が62.8%(199例)であった。術前あるいは術中に胆嚢癌と診断し得た割合は、隆起型では78.8%(93/118)、表面型では24.6%(49/199)であり、表面型は術前・術中診断率が有意に低かった(P<0.001)。早期胆嚢癌317例中315例が腺癌で、そのうち91.5%(286/315)が乳頭腺癌あるいは高分化型管状腺癌であった。癌の局所進展度別頻度は、Tis(M)癌もしくはT1a(M)癌が85.8%(272例)、T1b(MP)癌が14.2%(45例)であった。リンパ管浸潤をT1b(MP)癌の1例で認めたが、静脈浸潤、神経浸潤、リンパ節転移は早期胆嚢癌317例全例で陰性であった。本稿では、胆嚢の前癌病変、初期癌病変を含む早期胆嚢癌に関する学術的用語について言及し、従来の研究成果を概括することにより、早期胆嚢癌の病理組織学的特徴を解説する。(著者抄録)

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Language：Japanese   Publisher：新潟医学会  

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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：新潟医学会  

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【目的】大腸癌肝転移と肝内胆管癌は両者ともに腺癌であり、画像検査や腫瘍マーカー等も類似した所見を示すことが多い。今回我々は、術前に肝内胆管癌との鑑別が困難であり、切除標本の免疫組織化学により診断可能となった胆管浸潤を伴う大腸癌肝転移の2例を経験したので報告する。【対象・方法】対象となった2例はいずれも過去に大腸癌に対する根治手術を施行されていた。腹部CT検査で胆管浸潤を伴う肝腫瘤を指摘され、術前に大腸癌肝転移と肝内胆管癌との鑑別は困難であった。切除標本の免疫組織化学により、両者の鑑別診断を行った。【結果】症例1:71歳、男性。直腸癌Stage Iに対する手術施行後4年7ヵ月の腹部CT検査で肝右葉に腫瘤を指摘された。肝内胆管後区域枝および尾状葉枝に拡張を認め、胆管浸潤が疑われた。肝内胆管後区域枝および尾状葉枝に腫瘍栓を認め、肝右葉切除・尾状葉切除・肝外胆管切除が施行された。症例2:75歳、女性。上行結腸癌Stage IIに対する手術後2年5ヵ月の腹部CT検査で肝後区域に腫瘤を指摘された。大腸癌肝転移を疑われ、全身化学療法を施行されたが反応性は明らかでなく、腫瘤の胆管浸潤も認められるようになったため、肝右葉切除・肝外胆管切除が施行された。いずれの症例も、腫瘍細胞はCytokeratin(CK)7陰性、CK20陽性を示し、組織学的に大腸癌肝転移と診断された。【考察】胆管浸潤は肝内胆管癌に特徴的な画像所見とされている。今回経験した大腸癌肝転移の2例はいずれも胆管浸潤所見が認められ、肝内胆管癌との鑑別は画像上困難であった。両者の鑑別診断に際しては大腸癌既往に関する情報が重要であるが、大腸癌原発巣の切除から時間が経過した異時性再発例や化学療法への反応性が乏しい場合、術前診断は容易ではない。大腸癌肝転移と肝内胆管癌の病理診断において、免疫組織化学の有用性が報告されている。大腸上皮マーカーであるCK20と胆管上皮マーカーであるCK7の組み合わせにより正確な組織診断が可能となる。2例ともCK7陰性かつCK20陽性であり、大腸癌肝転移と診断する強い根拠となった。【結論】肝内胆管癌との鑑別が困難であった胆管浸潤を伴う大腸癌肝転移の2切除例を経験した。両者の鑑別診断にはCK7、CK20に対する免疫組織化学が有用である。免疫組織化学による正確な鑑別診断により、適切な薬物療法の選択が可能となる。(著者抄録)

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Language：Japanese   Publisher：(一社)日本肝胆膵外科学会  

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

画像診断が進歩した今日においても、良悪性の鑑別に苦慮する胆管狭窄は少なくない。当施設で経験した胆管狭窄153例中、術後の病理組織学的検査で良性胆管病変と診断された5例における臨床病理学的特徴を検討した。153例中148例は術後の病理組織学的検査で悪性腫瘍(肝外胆管癌110例、肝内胆管癌12例、胆嚢癌26例)と診断されたが、5例(3.3%)は良性胆管病変と診断された。術前診断の内訳は、肝内胆管癌2例、肝門部胆管癌3例であった。良性胆管狭窄の中にはIgG4関連硬化性胆管炎による胆管狭窄も少なからず存在し、ステロイドによる診断的治療が有用となる可能性がある。良性胆管狭窄はまれな病態であるが、術前に良悪性を確実に鑑別することは困難である。良悪性の鑑別困難な現状を考慮すれば、悪性を否定しえない胆管狭窄病変に対する治療は、十分なインフォームド・コンセントを行ったうえで外科切除を行うべきである。(著者抄録)

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Language：Japanese   Publisher：新潟医学会  

症例は69歳男性。下肢蜂窩織炎の精査中に膵頭部に腫瘤を指摘され当科紹介となった。腹部CT検査で膵頭部に早期濃染し持続濃染を呈する2cm弱の腫瘤を認めた。術前の内分泌学検査では、血中インスリン値4μU/L、血中ガストリン値132pg/mLと正常範囲内であり、非機能性膵神経内分泌腫瘍の術前診断で亜全胃温存膵頭十二指腸切除術を施行した。病理組織学検査では紡錘形の腫瘍細胞が様々な密度で混在し、免疫組織化学検査では、CD34陽性、bcl-2陽性、c-kit陰性、S-100陰性でありSolitary fibrous tumorと診断された。Solitary fibrous tumorは主に胸膜に発生する腫瘍であり、膵原発Solitary fibrous tumorの報告は稀であるため文献的考察を加えて報告する。(著者抄録)

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2014&ichushi_jid=J00990&link_issn=&doc_id=20140725060004&doc_link_id=%2Fdg3nigta%2F2014%2F012803%2F004%2F0121-0127%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdg3nigta%2F2014%2F012803%2F004%2F0121-0127%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Publishing type：Research paper (scientific journal)  

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Language：Japanese   Publisher：新潟医学会  

【目的】血液透析患者数の増加に伴い、腹部手術を要する血液透析患者が近年、増加している。本研究では、慢性腎不全による血液透析患者の腹部手術症例の術後成績からその問題点を明らかにする。【対象と方法】2011年1月から2012年12月までの2年間で当科で実施された手術1592例中、腹部手術を実施された血液透析患者13例(0.8%)を対象とした。その内訳は、待機手術6例(十二指腸乳頭部癌、胃カルチノイド、胆嚢癌、横行結腸癌、小腸潰瘍、胆嚢ポリープ、各々1例)、緊急手術7例(非閉塞性腸管虚血症2例、穿孔性腹膜炎・腹腔内膿瘍、S状結腸憩室穿孔、持続的腹膜透析カテーテル関連腹膜炎、脳死膵腎同時移植、出血性直腸ポリープ、各々1例)であった。待機手術症例と緊急手術症例との間で、術後合併症、術後在院死亡の発生率を比較した。【結果】待機手術症例では2例(33%)に術後合併症(麻痺性イレウス、胃内容排出遅延、各々1例)を認めたが、いずれも軽症で比較的早期に退院が可能であった。一方、緊急手術症例では3例(43%)に術後合併症(敗血症性ショック、敗血症性ショック+多臓器不全、腹腔内膿瘍・出血+下大静脈血栓+髄膜炎、各々1例)を認め、そのうち2例(緊急手術症例の29%)が在院死亡した。待機手術症例と比較して緊急手術症例では、術後合併症および在院死亡の発生率が高率であった。【結論】日常の透析管理や周術期管理の進歩により、血液透析患者の腹部待機手術は安全に施行されるようになったが、腹部緊急手術の術後短期成績は未だ不良である。その原因として、免疫力の低下、易感染性といった特徴をもつ血液透析患者では病態が早期に重篤化しやすいことが示唆される。血液透析患者の病態理解、早期診断・治療が、血液透析患者に対する腹部緊急手術の術後成績向上に必要と考えられる。(著者抄録)

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

Sorafenib is a multi-kinase inhibitor approved for hepatocellular carcinoma, but rarely causes tumor regression in patients with chronic liver diseases. To investigate whether growth factor-mediated signaling is involved in sorafenib resistance, HepG2 and PLC/PRF/5 hepatoma cells were exposed to epidermal growth factor (EGF), hepatocyte growth factor (HGF) or transforming growth factor-β (TGF-β) prior to treatment with sorafenib. Furthermore, to identify an effective combination treatment with sorafenib, growth factor-sensitized cells were treated with sorafenib alone or in combination with celecoxib, lovastatin or valproic acid (VPA). Trypan blue staining and Annexin V assays showed that the cytotoxic effect of sorafenib was inhibited by 15-54% in cells sensitized to TGF-β (P<0.05). Western blotting analysis showed that TGF-β significantly activated extracellular signal-regulated kinase (ERK)-mediated AKT signaling, and sorafenib failed to suppress both ERK and AKT in TGF-β-sensitized cells. The decreased anti-tumor effect of sorafenib was rescued by chemical inhibition of ERK and AKT. When TGF-β-sensitized cells were treated with sorafenib plus VPA, the levels of phosphorylated ERK and AKT were considerably suppressed and the numbers of dead cells were increased by 3.7-5.7-fold compared with those exposed to sorafenib alone (P<0.05). Moreover, low dose sorafenib-induced cell migration was effectively suppressed by combination treatment with sorafenib and VPA. Collectively, TGF-β/ERK/AKT signaling might play a critical role in sorafenib resistance in hepatoma cells, and combination treatment with VPA may be effective against this drug resistance.

PubMed

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

Sphingosine-1-phosphate (S1P) is a pleiotropic lipid mediator that regulates cell survival, migration, the recruitment of immune cells, angiogenesis, and lymphangiogenesis, all of which are involved in cancer progression. S1P is generated inside cancer cells by sphingosine kinases then exported outside of the cell into the tumor microenvironment where it binds to any of five G protein coupled receptors and proceeds to regulate a variety of functions. We have recently reported on the mechanisms underlying the "inside-out" signaling of S1P, its export through the plasma membrane, and its interaction with cell surface receptors. Membrane lipids, including S1P, do not spontaneously exchange through lipid bilayers since the polar head groups do not readily go through the hydrophobic interior of the plasma membrane. Instead, specific transporter proteins exist on the membrane to exchange these lipids. This review summarizes what is known regarding S1P transport through the cell membrane via ATP-binding cassette transporters and the spinster 2 transporter and discusses the roles for these transporters in cancer and in the tumor microenvironment. Based on our research and the emerging understanding of the role of S1P signaling in cancer and in the tumor microenvironment, S1P transporters and S1P signaling hold promise as new therapeutic targets for cancer drug development.

DOI： 10.1155/2014/651727

PubMed

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

Hepatitis B virus X (HBX) protein plays a crucial role in carcinogenesis, but its mechanism is unclear. The involvement of ataxia telangiectasia mutated (ATM) kinase in the enhanced redox system was investigated by examining the phosphorylation level of ATM in HBX gene-transfected cells and in transgenic mice following redox system manipulation by treatment with hydrogen peroxide (H2O2) or antioxidant. Western blotting and immunostaining showed that phospho-ATM was significantly increased by HBX both in vitro (3.2-fold; p<0.05) and in vivo (4-fold; p<0.05), and this effect was abrogated by antioxidant treatment. The level of PKC-δ in HBX-expressing cells was increased 3.5-fold compared to controls. Nuclear localized NF-E2-related factor 2 (Nrf2) was increased in HBX-expressing cells exposed to H2O2, but remained at lower levels after the treatment with rottlerin, KU55933, or caffeine. The levels of anti-oxidant molecules were increased in HBX expressing cells and in transgenic mice, indicating that HBX stimulates the Nrf2-mediated redox system. The levels of intracellular reactive oxygen species (ROS) were significantly increased in HBX-expressing cells treated with hydrogen peroxide in the presence of ATM inhibitor KU55933 or caffeine. Treatment of HBX-expressing cells with KU55933 or caffeine before the exposure to H2O2 increased the ratio of cell apoptosis to 33±4% (p<0.05) and 22±4% (p<0.05), respectively. Collectively, HBX stimulates the ATM-mediated PKC-δ/Nrf2 pathway, and maintains the enhanced activity of the redox system. Therefore, manipulating ATM kinase activity might be a useful strategy for treating HBX-induced carcinogenesis.

PubMed

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

Non-alcoholic steatohepatitis (NASH) is a recently identified chronic liver disease, which progresses to liver cirrhosis and hepatocellular carcinoma (HCC). As the number of patients studied to date has been limited, clinically useful prognostic biomarkers of NASH-related HCC have not been available. In this study, we investigated the status of a cell-cycle regulator, p27, in NASH-related HCC. p27 has been regarded as a prognostic factor in various types of cancer patients. A total of 22 cases with NASH-related HCC were analyzed for p27 protein expression, and phosphorylation at threonine 157 (T157) and serine 10 (S10) by immunohistochemical analysis. The correlation of p27 with tumor characteristics, disease-free survival (DFS), and overall survival was analyzed. p27 expression was decreased in 13 HCCs (59%), and was significantly correlated with enlarged tumor size (p = 0.01) and increased cell proliferation (p < 0.01). Phospho-p27 at T157 and S10 was detected in four (18%) and seven (32%) cases, respectively, and patients positive for phospho-p27 (S10) showed reduced DFS (hazard ratio 7.623, p = 0.016) by univariate analysis. Further studies with more patients are required to verify the usefulness of p27 as a biomarker for predicting tumor recurrence in NASH patients.

DOI： 10.3390/ijms141223499

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

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Language：Japanese   Publisher：(一社)日本外科感染症学会  

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Language：Japanese   Publisher：日本胆道学会  

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Language：Japanese   Publisher：新潟医学会  

【目的】本研究の目的は, 局所進展が高度な肝内胆管癌に対する術前化学療法の効果と周術期に及ぼす影響を明らかにすることにある. 【方法】当科で2009年1月から2012年8月までに術前の画像診断で根治切除が困難・不能と判断された症例に対して術前化学療法を行った5例を対象とした. 根治切除が困難・不能と判断した因子は, 高度局所進展(腹壁・胃への浸潤, 腹膜播種)が4例, 高度局所進展+大動脈周囲リンパ節転移が1例であった. 術前化学療法としては, gemcitabine(GEM)が2例, テガフール・ギメラシル・オテラシルカリウム配合剤(S-1)が1例, GEM+S-1が1例, GEM+S-1からGEM+cisplatinに変更が1例であった. 抗癌剤効果判定基準(RECISTガイドライン)に準じて術前化学療法の効果を判定した. 【成績】標的病変の抗癌剤効果判定は, 部分奏功(PR)が1例(GEM+S-1を施行し腫瘍縮小率68%), 安定(SD)が3例, 進行(PD)が1例であり, 奏功率は20%であった. Grade3の有害事象を1例に認めたが, 全例で術前化学療法前に立案していた術式の遂行が可能であった. 全例にR0切除が行われ, pStage Iが1例, pStage IVAが3例, pStage IVBが1例であった. 術後合併症を3例に認めた. その内訳は, 腹腔内膿瘍2例, 仮性動脈瘤破裂1例, 腸炎1例, リンパ漏1例(重複あり)であった. 術後在院死亡は認めなかった. 術前化学療法の効果判定がPRとSDであった2例が, 各々術後9か月, 14か月に原病死したが, 残り3例は生存中であった. 全症例の累積1年生存率は75%, 累積2年生存率は50%, 生存期間中央値は14か月であった. 【結論】局所進展が高度な肝内胆管癌に対する術前化学療法は安全に施行でき, 化学療法前に立案していた術式を遂行可能である. ただし, 術前化学療法の奏功率が低いこと, 奏功しないPD症例が存在することが臨床上の問題点として挙げられる.

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Language：Japanese   Publisher：新潟医学会  

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2013&ichushi_jid=J00990&link_issn=&doc_id=20130812030015&doc_link_id=%2Fdg3nigta%2F2013%2Fs12703%2F010%2F0159-0160%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdg3nigta%2F2013%2Fs12703%2F010%2F0159-0160%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：新潟医学会  

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Scopus

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Publishing type：Research paper (scientific journal)  

DOI： 10.5754/HGE12942

Web of Science

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Language：Japanese   Publisher：新潟医学会  

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2012&ichushi_jid=J00990&link_issn=&doc_id=20130423230018&doc_link_id=%2Fdg3nigta%2F2012%2Fs12612%2F008%2F0707-0707%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdg3nigta%2F2012%2Fs12612%2F008%2F0707-0707%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

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：(一財)日本消化器病学会  

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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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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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