記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1038/s41598-018-29144-9

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DOI： 10.1186/s12957-018-1454-y

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1186/s12957-018-1428-0

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The high heterogeneity of hepatocellular carcinomas (HCCs) complicates stratification of HCC patients for treatment. Therefore, it is necessary to establish a comprehensive panel of HCC biomarkers related to tumour behaviour and cancer prognosis. Resected HCCs from 251 patients were stained for hepatic progenitor cell (HPC) markers epithelial cell adhesion molecule (EpCAM), neural cell adhesion molecule (NCAM), delta-like 1 homolog (DLK1), and cytokeratin 19 (CK19). Staining patterns were analysed for their prognostic association with relapse-free survival and overall survival. α-Fetoprotein (AFP), lectin-reactive α-fetoprotein (AFP-L3), and des-γ-carboxy prothrombin (DCP) were assessed as indicators of HPC protein expression. Expression pattern of HPC markers correlated with tumour malignancy indicated by high AFP/AFP-L3 serum levels, more frequent vascular invasion, and poorer tumour differentiation. EpCAM expression, DCP ≥300 mAU/ml, age ≥60, and Child-Pugh score grade B or C were independent prognostic factors of poor outcome and were used in a new scoring system for HCC prognosis after operation. Expression of two or more HPC markers was a significant predictor of poor HCC outcome and serum levels of AFP/AFP-L3 correlated with the expression of HPC proteins. Our study paved the way for further elucidation of the association among HPC markers, serum tumour markers, and HCC clinical outcome for precision medicine.

DOI： 10.18632/oncotarget.25074

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Blackwell Publishing Asia  

DOI： 10.1002/jhbp.534

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Korean Society of Coloproctology  

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

DOI： 10.3393/ac.2017.06.14

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.asjsur.2018.01.003

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1200/PO.18.00097

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：IMPACT JOURNALS LLC  

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

DOI： 10.18632/oncotarget.20510

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Baishideng Publishing Group Co., Limited  

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

DOI： 10.5306/wjco.v8.i5.412

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.14740/jocmr3113w

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BIOMED CENTRAL LTD  

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

DOI： 10.1186/s13073-017-0484-3

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1186/s40792-017-0387-y

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

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

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：W B SAUNDERS CO-ELSEVIER INC  

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

DOI： 10.1016/j.humpath.2017.02.004

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：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.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1186/s40792-016-0264-0

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BIOMED CENTRAL LTD  

Background: Comprehensive genomic sequencing (CGS) has the potential to revolutionize precision medicine for cancer patients across the globe. However, to date large-scale genomic sequencing of cancer patients has been limited to Western populations. In order to understand possible ethnic and geographic differences and to explore the broader application of CGS to other populations, we sequenced a panel of 415 important cancer genes to characterize clinically actionable genomic driver events in 201 Japanese patients with colorectal cancer (CRC).
Methods: Using next-generation sequencing methods, we examined all exons of 415 known cancer genes in Japanese CRC patients (n = 201) and evaluated for concordance among independent data obtained from US patients with CRC (n = 108) and from The Cancer Genome Atlas-CRC whole exome sequencing (WES) database (n = 224). Mutation data from non-hypermutated Japanese CRC patients were extracted and clustered by gene mutation patterns. Two different sets of genes from the 415-gene panel were used for clustering: 61 genes with frequent alteration in CRC and 26 genes that are clinically actionable in CRC.
Results: The 415-gene panel is able to identify all of the critical mutations in tumor samples as well as WES, including identifying hypermutated tumors. Although the overall mutation spectrum of the Japanese patients is similar to that of the Western population, we found significant differences in the frequencies of mutations in ERBB2 and BRAF. We show that the 415-gene panel identifies a number of clinically actionable mutations in KRAS, NRAS, and BRAF that are not detected by hot-spot testing. We also discovered that 26% of cases have mutations in genes involved in DNA double strand break repair pathway. Unsupervised clustering revealed that a panel of 26 genes can be used to classify the patients into eight different categories, each of which can optimally be treated with a particular combination therapy.
Conclusions: Use of a panel of 415 genes can reliably identify all of the critical mutations in CRC patients and this information of CGS can be used to determine the most optimal treatment for patients of all ethnicities.

DOI： 10.1186/s13073-016-0387-8

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

Introduction: The elucidation of the clinical impact of comorbidities is important to optimize the treatment and follow-up strategy in oesophageal cancer. We aimed to clarify the surgical and long-term outcomes following oesophagectomy in oesophageal cancer patients with comorbidity.
Methods: A total of 658 consecutive patients who underwent oesophagectomy for oesophageal cancer between 1985 and 2008 at our institution were enrolled. Based on the criteria of comorbidity as we defined it, we retrospectively reviewed and compared the surgical outcomes and survival between the comorbid (n= 251) and non-comorbid group (n=407).
Results: Postoperative morbidity and mortality were not significantly different between the two groups. The 5-year overall survival rate of the comorbid group was significantly lower (39.3% vs. 45.2%, adjusted HR = 1.31, 95% CI: 1.07-1.62) but the 5-year disease-specific survival rate was not significantly different between the comorbid and non-comorbid groups (53.9% vs. 53.1%, adjusted HR = 1.11, 95% CI: 0.86 -1.42). The 5-year incidence rate of death from other diseases in the comorbid group was significantly higher than that in the non-comorbid group (26.7% vs. 14.8%, P < 0.01). The leading cause of death from other diseases was pneumonia.
Conclusions: Oesophagectomy in oesophageal cancer patients with comorbidity can be safely performed. However, the overall survival after oesophagectomy in these patients was unfavorable because of the high incidence of death from other diseases, especially pneumonia. (C) 2016 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.ijsu.2016.10.041

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：CHURCHILL LIVINGSTONE  

Background and aims: Transthoracic esophagectomy using 3-field lymphadenectomy (TTE-3FL) for esophageal cancer is one of the most aggressive gastrointestinal surgeries. Early enteral nutrition (EN) for TTE-3FL patients is useful and valid for early recovery; however, EN using a fat-containing formula risks inducing chyle leak. In the present study, we retrospectively examined esophageal cancer patients treated byTTE-3FL and administered postoperative EN to elucidate the validity of lowering the fat levels in elemental formulas to prevent postoperative chyle leak and improve postoperative recovery.
Methods: A total of 74 patients who received TTE-3FL for esophageal cancer were retrospectively examined. Patients were classified into two groups according to the type of postoperative EN: Group LF patients received a low-fat elemental formula, and Group F patients received a standard fat-containing polymeric formula. The following clinical factors were compared between the groups: EN start day, maximum EN calories administered, duration of respirator use, length of ICU stay, incidence of postoperative infectious complications, use of parenteral nutrition (PN), and incidence of postoperative chyle leak.
Results: Patients in Group LF were started on EN significantly earlier after surgery and they consumed significantly higher maximum EN calories compared to Group F patients (P < 0.01). Duration of respirator use and length of ICU stay were also significantly shorter, and TPN was used significantly less in Group LF compared to Group F (P < 0.05). Postoperative chyle leak was observed in six patients in total (8.1%); five patients in Group F and one patient in Group LF, although there was no significant difference in frequency of chyle leak per patient between Group LF and Group F.
Conclusions: Early EN using low-fat elemental formula after esophagectomy with three-field lymphadenectomy was safe and valid for postoperative recovery and potentially useful in preventing chyle leak. (C) 2016 The Authors. Published by Elsevier Ltd.

DOI： 10.1016/j.clnu.2016.03.018

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BIOMED CENTRAL LTD  

Background: Meigs' syndrome is defined as the co-existence of benign ovarian fibroma or fibroma-like tumor, ascites, and pleural effusion. In contrast, pseudo-Meigs' syndrome is defined as the co-existence of other ovarian or pelvic tumors, ascites, and pleural effusion. In Meigs' and pseudo-Meigs' syndromes, ascites and pleural effusion resolve promptly after the complete resection of the ovarian or pelvic tumor(s). Secondary ovarian tumors from colorectal gastrointestinal metastases rarely cause pseudo-Meigs' syndrome; only 11 cases of pseudo-Meigs' syndrome secondary to colorectal cancers have been reported in the literature. Therefore, the prognosis and etiology of pseudo-Meigs' syndrome caused by ovarian metastasis from colorectal cancers remain unclear.
Case presentation: We report here a rare case of pseudo-Meigs' syndrome caused by ovarian metastases from sigmoid colon cancer with long-term survival. A 47-year-old woman presented with abdominal distention of 1month duration. She developed acute dyspnea 2 weeks after the initial presentation. Colonoscopy and computed tomography revealed sigmoid colon cancer with an ovarian metastasis, along with massive ascites and bilateral pleural effusion. Emergency operation, including bilateral oophorectomy and sigmoidectomy, was performed. Subsequently, ascites and bilateral pleural effusion resolved rapidly. Curative hepatic resection was performed for liver metastases 29 months after the first operation, and as of this writing, the patient is alive with no evidence of a disease 78 months after the first operation. In general, colorectal cancer with ovarian metastasis is hard to cure, and long-term survival in patients with colorectal cancer with pseudo-Meigs' syndrome is rare. Our experience suggests that curative resection for pseudo-Meigs' syndrome caused by ovarian metastasis from colorectal cancer may offer long-term survival.
Conclusions: Our experience suggests that pseudo-Meigs' syndrome can occur in a patient with colorectal cancer after metastasis to the ovaries, causing massive ascites and pleural effusion. Aggressive treatment, including R0 resection, for this disease if allowed by the patient's general condition may offer long-term survival.

DOI： 10.1186/s12957-016-1040-0

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

The presence of extramural tumor deposits without lymph node structure (EX) is an important prognostic factor for patients with colorectal cancer. However, the clinical significance of EX in the lateral pelvic lymph node area (LP-EX) remains unclear. This study aimed to determine the prognostic implications of LP-EX for patients with low rectal cancer.
This retrospective study involved 172 consecutive patients with stage 2 or 3 low rectal cancer who underwent curative surgery including lateral pelvic lymph node (LPLN) dissection. The patients were classified into the following three groups according to the metastatic status of the LPLN area: patients without metastasis (no-LP-M group), patients with lymph node metastasis (LP-LNM group), and patients with EX (LP-EX group). Potential prognostic factors of overall survival (OS) and relapse-free survival (RFS) were identified in uni- and multivariate analyses.
Classification assigned 131 patients (76 %) to the no-LP-M group, 27 patients (16 %) to the LP-LNM group, and 14 patients (8 %) to the LP-EX group. The 5-year OS rate was 80.3 % in the no-LP-M group, 61.1 % in the LP-LNM group, and 34.9 % in the LP-EX group (P < 0.001). The corresponding 5-year RFS rates were 62.2, 33.8, and 14.3 %, respectively (P < 0.001). A multivariate Cox proportional hazards regression analysis showed that the presence of LP-EX was an independent prognostic factor for OS (P = 0.006) and RFS (P = 0.001).
The LP-EX classification is a useful pathologic parameter that can be used to stratify patients with metastasis in the LPLN area.

DOI： 10.1245/s10434-016-5379-9

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記述言語：英語   出版者・発行元：AMER SOC CLINICAL ONCOLOGY  

DOI： 10.1200/JCO.2016.34.15_suppl.e15121

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記述言語：英語   出版者・発行元：AMER SOC CLINICAL ONCOLOGY  

DOI： 10.1200/JCO.2016.34.15_suppl.e13125

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

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.
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.
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 a parts per thousand yen2; 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.
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

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：E-CENTURY PUBLISHING CORP  

This study aimed to histologically characterize microscopic tumor invasion of the vasculo-biliary sheaths in perihilar cholangiocarcinoma so as to determine the primary tumor site and to clarify clinicopathologic differences according to the primary site. A retrospective analysis was conducted of 52 patients who underwent resection for perihilar cholangiocarcinoma involving both the hepatic hilus and the liver, verified histologically. Histologic features of the vasculo-biliary sheath invasion were evaluated by double staining with hematoxylin-eosin to assess general morphology and Victoria Blue to detect the elastic fibers of the vasculo-biliary sheaths. The perihilar cholangiocarcinomas were classified into extrahepatic-type (34 patients), featuring an extrahepatic component involving the liver, and intrahepatic-type (18 patients), featuring an intrahepatic component involving the hepatic hilus. Hemihepatectomy with extrahepatic bile duct resection was the most common surgical procedure. Tumor size (p = 0.002), pN classification (p = 0.005), and pM classification (p = 0.023) were significant independent prognostic factors. The primary site was not significantly associated with survival after resection (p = 0.214), as patients with extrahepatictype tumors had a cumulative 5-year survival rate of 32%, compared with 28% for patients with intrahepatic-type tumors. Double staining with hematoxylin-eosin and Victoria Blue permits histologic discrimination between tumors of extrahepatic and intrahepatic origin, and thereby determination of the primary tumor site in clinical cases of perihilar cholangiocarcinoma. Combining extrahepatic-type and intrahepatic-type tumors under the term perihilar cholangiocarcinoma is valid clinically, as these tumors show comparable surgical outcomes with similar clinical management.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：E-CENTURY PUBLISHING CORP  

NAD(P) H:quinone oxidoreductase-1 (NQO1) confers resistance to anticancer agents, particularly to oxidative stress inducers such as cisplatin or 5-fluorouracil in malignant tumors. Here we evaluated the association between NQO1 expression in esophageal squamous cell carcinoma (ESCC) cells and the patients' responses to preoperative chemotherapy with cisplatin and 5-fluorouracil (CF), and we elucidated the prognostic significance of NQO1 expression in ESCC patients. We retrospectively analyzed the cases of 40 patients who underwent preoperative CF therapy followed by curative esophagectomy with lymphadenectomy. Immunohistochemistry of the surgically resected specimens was conducted using the primary monoclonal antibody against NQO1. Eighteen of the 40 patients (45%) had tumors that showed high NQO1 expression (NQO1-high group). The poorer histological response to preoperative CF therapy was dominant in the NQO1-high group compared to the NQO1-low group (72% and 45%, respectively) but the difference was not significant (P=0.09). The 3-year recurrence-free survival rate after esophagectomy in the NQO1-high group was significantly lower compared to the NQO1-low group (39% vs. 76%; P<0.01). A Cox proportional hazards model revealed that high NQO1 expression was an independent unfavorable prognostic factor (HR=3.53; P=0.02) as was pN3 (HR=14.7; P<0.01). The immunohistochemical evaluation of NQO1 expression has potential to predict the treatment response and prognosis in patients who undergo preoperative CF therapy followed by esophagectomy for ESCC.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：E-CENTURY PUBLISHING CORP  

MED12 is a transcriptional mediator complex subunit, which negatively regulates the transforming growth factor beta (TGF-beta) pathway. The TGF-beta pathway plays a major role in the induction of epithelial-mesenchymal transition 9EMT). MED12 loss induces activation of the TGF-beta pathway, resulting in EMT and drug resistance to epidermal growth factor receptor (EGFR)-targeted therapy. We aimed to investigate the clinical significance of MED12 loss detected by immunohistochemistry in patients with colorectal cancer (CRC). A total of 100 patients diagnosed with stage I-IV CRC were enrolled in this retrospective study. MED12 expression was evaluated immunohistochemically, and classified as either positive (>= 20%) or negative (<20%) with regard to the percentage of immunoreactive cells. The relationships between MED12 loss and clinicopathological characteristics and RAS mutation status were analyzed. Overall, 79 and 21 patients were classified as MED12 positive and MED12 negative, respectively. MED12 negativity was significantly associated with tumor budding (P = 0.034), N category (P = 0.010), and M category (P = 0.031). Among stage IV CRC patients, 18 of 31 patients had the RAS wild-type gene; 6 of these patients were MED12 negative, and were considered to have the potential for resistance to EGFR-targeted therapy despite the presence of the wild-type gene. In conclusion, MED12 loss is associated with tumor budding, nodal metastasis, and distant metastasis in patients with CRC, suggesting that MED12 loss induces activation of the TGF-beta pathway resulting in EMT. Future treatment strategies focusing on patients MED12 loss may improve the prognosis of patients with CRC.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1186/s40792-015-0073-x

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記述言語：英語   出版者・発行元：ELSEVIER SCIENCE INC  

DOI： 10.1016/j.jamcollsurg.2014.07.852

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：E-CENTURY PUBLISHING CORP  

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-delta 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-delta/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.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY  

The aim of this study was to clarify the association between the DNA damage response mediated by p53-binding protein 1 (53BP1) in residual carcinoma in situ at ductal stumps and local recurrence in patients undergoing resection for extrahepatic cholangiocarcinoma.
A retrospective analysis was conducted of 11 patients with positive ductal margins with carcinoma in situ. To evaluate the early DNA damage response, the nuclear staining pattern of 53BP1 was examined by immunofluorescence. TUNEL analysis was used to calculate the apoptotic index.
Of the 11 tumor specimens of carcinoma in situ, seven showed diffuse localization of 53BP1 in nuclei (53BP1 inactivation) and four showed discrete nuclear foci of 53BP1 (53BP1 activation); the apoptotic index was significantly decreased in the seven tumor specimens with 53BP1 inactivation compared to the four with 53BP1 activation (median apoptotic index, 1 vs. 22 %; p = 0.003). The cumulative probability of local recurrence was significantly higher in patients with 53BP1 inactivation than in patients with 53BP1 activation (cumulative 5-year local recurrence rate, 60 vs. 0 %; p = 0.019).
Clinically evident local recurrence of residual carcinoma in situ at ductal stumps is closely associated with 53BP1 inactivation and decreased apoptosis.

DOI： 10.1007/s00534-012-0539-1

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

Background and Aim The aim of this study was to elucidate the risk of subsequent biliary malignancy in patients undergoing cyst excision for congenital choledochal cysts. Methods A retrospective analysis of 94 patients who had undergone cyst excision for congenital choledochal cysts was conducted. The median age at the time of cyst excision and median follow-up time after cyst excision were 7 years and 181 months, respectively. Results Biliary tract cancer developed in four patients at 13, 15, 23, and 32 years after cyst excision. The cumulative incidences of biliary tract cancer at 15, 20, and 25 years after cyst excision were 1.6%, 3.9%, and 11.3%, respectively. The sites of biliary tract cancer were the intrahepatic (n?=?2), hilar (n?=?1), and intrapancreatic (n?=?1) bile ducts. Of the four patients with biliary tract cancer after cyst excision, three patients underwent surgical resection and one patient received chemo-radiotherapy. The overall cumulative survival rates after treatment in the four patients with biliary tract cancer were 50% at 2 years and 25% at 3 years, with a median survival time of 15 months. Conclusions The risk of subsequent biliary malignancy in patients undergoing cyst excision for congenital choledochal cysts seems to be relatively high in the long-term. The risk of biliary malignancy in the remnant bile duct increases more than 15 years after cyst excision. Despite an aggressive treatment approach for this condition, subsequent biliary malignancy following cyst excision for congenital choledochal cysts shows an unfavorable outcome.

DOI： 10.1111/j.1440-1746.2012.07260.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SOUTHEASTERN SURGICAL CONGRESS  

Discrimination between benign and malignant biliary strictures is difficult, with 5.2 to 24.5 per cent of biliary strictures proving to be benign after histological examination of the resected specimen. This study aimed to evaluate the clinicopathological features of benign biliary strictures in patients undergoing resection for presumed biliary malignancy. From January 1990 to August 2010, 5 of 153 (3.3%) patients who had undergone resection after a preoperative diagnosis of biliary malignancy had a final histological diagnosis of benign biliary stricture. The infiltration of immunoglobulin G4-positive plasma cells was evaluated by immunohistochemistry. None of the five patients had a history of trauma or earlier hepatobiliary surgery and all five underwent hemihepatectomy (combined with extrahepatic bile duct resection in three patients). Postoperative morbidity was recorded in two patients (transient cholangitis and biliary fistula), but there was no postoperative mortality. Histological re-examination identified immunoglobulin G4-related sclerosing cholangitis (n = 2) and nonspecific fibrosis/inflammation (n = 3). No preoperative clinical or radiographic features were identified that could reliably distinguish patients with benign biliary strictures from those with biliary malignancies. Although benign biliary strictures are rare, differentiating benign strictures from malignancy remains problematic. Thus, the treatment approach for biliary strictures should remain surgical resection for presumed biliary malignancy.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：H G E UPDATE MEDICAL PUBLISHING S A  

Major hepatectomy combined with extrahepatic bile duct resection has gained acceptance as a standard radical procedure for hilar cholangiocarcinoma. Here, we describe an operative technique, "taping of the right hepatic artery behind Calot's triangle", for assessing the resectability of hilar lesions for which left-sided hepatectomy is planned. Briefly, after retracting the gallbladder anteriorly, the lateral peritoneum of the hepatoduodenal ligament is incised longitudinally (3-4cm in length) behind Calot's triangle and just to the left of the fissure of Ganz. By dividing the adipose tissue, the distal portion of the right hepatic artery is identified and secured with tape. Any suspicious tissues around the right hepatic artery should be submitted to frozen-section analysis. If no cancer cells were found, the planned resection goes ahead. Conversely, if they were found, the resection should be abandoned. Since 2003, 14 patients for whom left-sided hepatectomy was planned for hilar cholangio-carcinoma involvement, underwent this technique. Three patients were judged to have irresectable tumors and the planned resection could be avoided. In conclusion, this simple technique, isolation of the right hepatic artery behind Calot's triangle before starting resection, should be applied to all hilar malignancies when a left-sided hepatectomy is planned.

DOI： 10.5754/hge12240

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：H G E UPDATE MEDICAL PUBLISHING S A  

Background/Aims: This study aimed to evaluate whether wedge resection or S4bS5 resection was the more beneficial hepatectomy procedure for patients with locally advanced gallbladder carcinoma. Methodology: A retrospective analysis of 70 patients who underwent either wedge resection (n=58) or S4bS5 resection (n=12) for locally advanced gallbladder carcinoma without clinically evident liver metastases was conducted. Clinicopathological characteristics, histological features of hepatic invasion and surgical outcomes were analyzed. Results: Sixteen patients had tumors with hepatic invasion. Of the 16 patients with hepatic invasion, 6 had direct liver invasion alone and 10 had portal tract invasion featuring intrahepatic stromal invasion (n=5), intrahepatic lymphatic invasion (n=4) and intrahepatic venous invasion (n=1). The hepatectomy procedure was not significantly associated with survival after resection (p=0.518) as patients who underwent wedge resection showed an overall cumulative 3-year survival rate of 74% compared with 60% for patients who underwent S4bS5 resection. The Cox proportional hazard regression analysis revealed that pT classification (p<0.001), pM classification (p=0.001) and resection of the extrahepatic bile duct (p=0.048) were independently significant factors associated with survival after resection. Conclusions: Hepatectomy procedure may not significantly affect surgical outcomes in patients with gallbladder carcinoma. Partial hepatectomy involving the gallbladder bed is critical due to possible tumor cells.

DOI： 10.5754/hge12097

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BAISHIDENG PUBLISHING GROUP INC  

AIM: To delineate indications and limitations for "extended" radical cholecystectomy for gallbladder cancer: a procedure which was instituted in our department in 1982.
METHODS: Of 145 patients who underwent a radical resection for gallbladder cancer from 1982 through 2006, 52 (36%) had an extended radical cholecystectomy, which involved en bloc resection of the gallbladder, gallbladder fossa, extrahepatic bile duct, and the regional lymph nodes (first- and second-echelon node groups). A retrospective analysis of the 52 patients was conducted including at least 5 years of follow up. Residual tumor status was judged as no residual tumor (R0) or microscopic/macroscopic residual tumor (R1-2). Pathological findings were documented according to the American Joint Committee on Cancer Cancer Staging Manual (7th edition).
RESULTS: The primary tumor was classified as pathological T1 (pT1) in 3 patients, pT2 in 36, pT3 in 12, and pT4 in 1. Twenty-three patients had lymph node metastases; 11 had a single positive node, 4 had two positive nodes, and 8 had three or more positive nodes. None of the three patients with pT1 tumors had nodal disease, whereas 23 of 49 (47%) with pT2 or more advanced tumors had nodal disease. One patient died during the hospital stay for definitive resection, giving an in-hospital mortality rate of 2%. Overall survival (OS) after extended radical cholecystectomy was 65% at 5 years and 53% at 10 years in all 52 patients. OS differed according to the pT classification (P < 0.001) and the nodal status (P = 0.010). All of 3 patients with pT1 tumors and most (29 of 36) patients with pT2 tumors survived for more than 5 years. Of 12 patients with pT3 tumors, 8 who had an R1-2 resection, distant metastasis, or extensive extrahepatic organ involvement died soon after resection. Of the remaining four pT3 patients who had localized hepatic spread through the gallbladder fossa and underwent an R0 resection, 2 survived for more than 5 years and another survived for 4 years and 2 mo. The only patient with pT4 tumor died of disease soon after resection. Among 23 node-positive patients, 11 survived for more than 5 years, and of these, 10 had a modest degree of nodal disease (one or two positive nodes).
CONCLUSION: Extended radical cholecystectomy is indicated for pT2 tumors and some pT3 tumors with localized hepatic invasion, provided that the regional nodal disease is limited to a modest degree (up to two positive nodes). Extensive pT3 disease, pT4 disease, or marked nodal disease appears to be beyond the scope of this radical procedure. (C) 2012 Baishideng. All rights reserved.

DOI： 10.3748/wjg.v18.i34.4736

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：H G E UPDATE MEDICAL PUBLISHING S A  

Aggressive radical resection is advocated for gallbladder cancer. However, this is a disease of the elderly and some patients have comorbid disease(s) and/or a debilitated condition that may preclude such an aggressive treatment strategy. Here, we describe a minimum radical procedure for gallbladder cancer, termed as "full-thickness cholecystectomy with limited lymphadenectomy". This procedure comprises full-thickness resection of the gallbladder (cholecystectomy combined with removal of the entire cystic plate) and removal of the first-echelon lymph nodes (the pericholedochal and cystic duct node groups). Since 1992, 12 consecutive patients with advanced age and/or comorbid disease(s) underwent the described procedure for tumors confined to the gallbladder wall and with no gross evidence of distant metastases/nodal disease, resulting in no in-hospital mortality or recurrent disease. The median overall survival was 229 months with a cumulative 5-year survival of 100%. In conclusion, the minimal radical resection procedure is safe and effective for early-stage gallbladder cancer. This less invasive procedure can be applied to patients with advanced age and/or comorbid disease(s), provided that the tumor is apparently confined to the gallbladder wall and has no gross evidence of distant metastases/nodal disease.

DOI： 10.5754/hge12276

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BAISHIDENG PUBLISHING GROUP INC  

AIM: To define the rational extent of regional lymphadenectomy for gallbladder cancer and to clarify its effect on long-term survival.
METHODS: A total Of 152 patients with gallbladder cancer who underwent a minimum of "extended" portal lymph node dissection (defined as en bloc removal of the first-and second-echelon nodes) from 1982 to 2010 were retrospectively analyzed. Based on previous studies, regional lymph nodes of the gallbladder were divided into first-echelon nodes (cystic duct or pericholedochal nodes), second-echelon nodes (node groups posterosuperior to the head of the pancreas or around the hepatic vessels), and more distant nodes.
RESULTS: Among the 152 patients (total of 3352 lymph nodes retrieved, median of 19 per patient), 79 patients (52%) had 356 positive nodes. Among node-positive patients, the prevalence of nodal metastasis was highest in the pericholedochal (54%) and cystic duct (38%) nodes, followed by the second-echelon node groups (29% to 19%), while more distant node groups were only rarely (5% or less) involved. Disease-specific survival after R0 resection differed according to the nodal status (P < 0.001): most node-negative patients achieved long-term survival (median, not reached; 5-year survival, 80%), whereas among node-positive patients, 22 survived for more than 5 years (median, 37 mo; 5-year survival, 43%).
CONCLUSION: The rational extent of lymphadenectomy for gallbladder cancer should include the first- and second-echelon nodes. A considerable proportion of node-positive patients benefit from such aggressive lymphadenectomy. (C) 2012 Baishideng. All rights reserved.

DOI： 10.3748/wjg.v18.i22.2775

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BIOMED CENTRAL LTD  

Background: Assessment of lymph node status is a critical issue in the surgical management of gallbladder cancer. The aim of this study was to compare the anatomical location of positive nodes, number of positive nodes, and lymph node ratio (LNR) as prognostic predictors in gallbladder cancer.
Methods: We conducted a retrospective analysis of 135 patients with gallbladder cancer who underwent a radical resection with regional lymphadenectomy. A total of 2,245 regional lymph nodes were retrieved (median, 14 per patient). The location of positive nodes was classified according to the AJCC staging manual (7th edition). 'Optimal' cutoff values were determined for the number of positive nodes and LNR based on maximal chi(2) scores calculated with the Cox proportional hazards regression model.
Results: Lymph node metastasis was found histologically in 59 (44%) patients. The 'optimal' cutoff values for the number of positive nodes and LNR were determined to be three nodes and 10%, respectively. Univariate analysis identified location of positive nodes (pN0, pN1, pN2; P < 0.001), number of positive nodes (0, 1 to 3, >= 4; P < 0.001), and LNR (0%, 0 to 10%, >10%; P < 0.001) as significant prognostic factors. Multivariate analysis identified number of positive nodes as an independent prognostic factor (P = 0.004); however, location of positive nodes and LNR failed to remain as an independent variable.
Conclusions: The number of positive lymph nodes better predicts patient outcome after resection than either the location of positive lymph nodes or LNR in gallbladder cancer. Dividing the number of positive lymph nodes into three categories (0, 1 to 3, or >= 4) is valid for stratifying patients based on the prognosis after resection.

DOI： 10.1186/1477-7819-10-87

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記述言語：英語   出版者・発行元：MOSBY-ELSEVIER  

DOI： 10.1016/j.surg.2010.08.010

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：E-CENTURY PUBLISHING CORP  

In the present retrospective study, we tested the hypothesis that neoadjuvant chemotherapy (NAC) as a treatment for patients with colorectal carcinoma liver metastases (CRLM) may reduce intrahepatic micrometastases. The incidence and distribution of intrahepatic micrometastases were determined in specimens resected from 63 patients who underwent hepatectomy for CRLM (21 treated with NAC and 42 without). In addition, the therapeutic efficacy of NAC was evaluated histologically. Intrahepatic micrometastases were defined as microscopic lesions spatially separated from the gross tumor. The distance from these lesions to the border of the hepatic tumor was measured on histological specimens and the density of intrahepatic micrometastases (number of lesions/mm(2)) was determined in regions close to (<1 cm) the gross hepatic tumor. Of the 21 patients treated with NAC, 13 were identified as having a partial response according to the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines; thus, the overall response rate was 62%. Histologic evaluation of the therapeutic efficacy of NAC was significantly associated with tumor response to NAC according to the RECIST guidelines (p=0.048). In all, 260 intrahepatic micrometastases were detected in 39 patients (62%). Intrahepatic micrometastases were less frequently detected in NAC-treated patients than in untreated patients (5/21 [24%] vs. 34/42 [81%], respectively; p<0.001). There were no significant differences in the distance and density of intrahepatic micrometastases between the two groups (p=0.313 and p=0.526, respectively). In conclusion, NAC reduces the incidence of intrahepatic micrometastases in patients with CRLM, but NAC has no significant effect on their distribution when intrahepatic micrometastases are present.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

This study was intended to compare the prognostic power of the number of positive lymph nodes with that of the lymph node ratio in patients with ampullary carcinoma.
A retrospective analysis was conducted of the medical records of 71 consecutive patients with ampullary carcinoma who underwent pancreaticoduodenectomy with regional lymph node dissection. A total of 2151 lymph nodes were dissected (median: 28 nodes per patient) and examined histologically. Cutoff points were determined for both the number of positive nodes and the lymph node ratio using chi(2) scores calculated with the Cox proportional hazards regression model.
Lymph node metastasis was found in 34 patients. The best cutoff point for the number of positive nodes was identified as three nodes, and that for the lymph node ratio was identified as 10%. Univariate analysis revealed both the number of positive nodes (0, 1-3, or a parts per thousand yen4; P < 0.0001) and the lymph node ratio (0%, 0-10%, or > 10%; P < 0.0001) as significant prognostic factors. Multivariate analysis identified the number of positive nodes as an independent prognostic factor (P < 0.001), whereas the lymph node ratio failed to remain as an independent variable. The cumulative 5-year survival rates were 85% for patients with 0 positive nodes, 63% for patients with 1-3 positive nodes, and 0% for patients with a parts per thousand yen4 positive nodes (P < 0.0001).
The number of positive lymph nodes better predicts the outcome after resection than the lymph node ratio in patients with ampullary carcinoma.

DOI： 10.1007/s00268-011-1175-7

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：H G E UPDATE MEDICAL PUBLISHING S A  

Background/Aims: Ribonucleotide reductase M1 (RRM1) is a key molecule for gemcitabine resistance. This study evaluated the immunohistochemical expression of RRM1 in resected specimens of intrahepatic cholangiocarcinoma (ICC) and investigated the efficacy of gemcitabine-based neoadjuvant chemotherapy in relation to RRM1 expression in tumors.
Methodology: A retrospective analysis was conducted on 34 consecutive Japanese patients who underwent resection of ICC. Of the 34 patients, 2 were treated with neoadjuvant chemotherapy consisting of gemcitabine 800mg/m(2) every 2 weeks to address extrahepatic tumor extension. Expression of RRM1 in tumor specimens was assessed using immunohistochemistry and was classified as either positive or negative.
Results: RRM1-positive expression was detected in 19/34 (56%) tumor specimens. Two patients were treated with gemcitabine-based neoadjuvant chemotherapy; one had a tumor specimen showing RRM1-positive expression and showed a 14% tumor reduction rate (stable disease); another patient had a tumor showing RRM1-negative expression and showed a 68% tumor reduction rate (partial response). Surgical procedures planned before administration of neoadjuvant chemotherapy were performed in both patients.
Conclusions: Neoadjuvant chemotherapy with gemcitabine for locally advanced ICC was well tolerated and did not impair planned surgical resections. Tumor expression of RRM1 may determine the efficacy of gemcitabine-based chemotherapy for patients with ICC.

DOI： 10.5754/hge11175

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

The present study investigated outcomes following surgical resection of hepatocellular carcinoma (HCC) in nonalcoholic fatty liver disease (NAFLD).
Patients (n = 225) undergoing resection for HCC were divided into three groups: hepatitis C viral group (n = 147), hepatitis B viral group (n = 61), and NAFLD group (n = 17). Clinicopathological characteristics and surgical outcomes were analyzed retrospectively.
Patients in the NAFLD group were older (P < 0.001), with a higher body mass index (P < 0.001) and larger tumors (P = 0.002) than patients who were positive for hepatitis viral markers. Eight patients in the NAFLD group were found to have nonalcoholic steatohepatitis (NASH) histologically. Postoperative morbidity and 30-day mortality rates were significantly higher in the NAFLD group (59% and 12%, respectively) than in the hepatitis C viral (31% and 0.7%, respectively) and hepatitis B viral (28% and 3.3%; P = 0.043 and P = 0.016, respectively) groups. All deaths in the NAFLD group were in patients with NASH-related cirrhosis who had undergone right hemihepatectomy. Survival after resection was comparable among the three groups (P = 0.391), but patients with NAFLD showed better disease-free survival on univariate (P = 0.048) and multivariate (P = 0.020) analyses.
Surgical resection may provide a survival benefit for patients with NAFLD-related HCC. Patients with NASH-related cirrhosis undergoing major hepatic resection should be treated carefully.

DOI： 10.1007/s11605-011-1540-8

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPANDIDOS PUBL LTD  

P53-binding protein 1 (53BP1) is an early DNA damage response-protein that is rapidly recruited to sites of DNA. double-strand breaks. The presence of 53BP1 nuclear foci can be considered as a cytologic marker for endogenous double-strand breaks reflecting genomic instability. This study aimed to clarify the early DNA damage response mediated by 53BP1 in tumor specimens of ductal resection margins and to elucidate its predictive value for clinically evident local recurrence at ductal stumps in 110 patients undergoing resection for extrahepatic cholangiocarcinoma. The ductal resection margin status was classified as negative (85 patients), positive with carcinoma in situ (14 patients), or positive with invasive carcinoma (11 patients). The nuclear staining pattern of 53BP1 was evaluated by immunofluorescence. TUNEL analysis was used to calculate apoptotic index. Ductal margin status was the only independent risk factor for local recurrence (P=0.001). The cumulative probability of local recurrence at 5 years was 10%, 40% and 100% in patients with negative ductal margins, positive with carcinoma in situ and positive with invasive carcinoma, respectively (P<0.001). Of the 14 tumor specimens of carcinoma in situ, 10 showed diffuse localization of 53BP1 in nuclei (53BP1 inactivation) and 4 showed discrete nuclear Foci of 53BP1 (53BP1 activation). All 11 tumor specimens of invasive carcinoma showed 53BP1 inactivation. Apoptotic index was markedly decreased in tumor specimens with 53BP1 inactivation compared to those with 53BP1 activation (median index, 0% vs. 22%; P<0.001). Among 14 patients with residual carcinoma in situ, the cumulative probability of local recurrence was significantly higher in patients with 53BP1 inactivation than in patients with 53BP1 activation (60% vs. 0% at 5 years; P=-0.020). In conclusion, after resection for extrahepatic cholangiocarcinoma, clinically evident local recurrence at ductal stumps is closely associated with 53BP1 inactivation and decreased apoptosis.

DOI： 10.3892/ijo.2011.959

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPANDIDOS PUBL LTD  

Ewing sarcoma/primitive neuroectodermal tumors (ES/PNETs) may arise in bone or soft tissue; however, these tumors rarely originate in the stomach. To the best of our knowledge, only four cases have previously been reported in the English-language literature. A 41-year-old Japanese woman was admitted with abdominal pain and underwent gastrectomy to remove the primary tumor. Immunohistochemistry, chromosomal karyotype and molecular analysis using reverse transcription-polymerase chain reaction were performed in the tumor specimens obtained. Tumor cells showed positive immunoreactivity for CD99, vimentin, CD117 (c-kit), S100, chromogranin A and synaptophysin. The tumor was a gastric ES/PNET with the EWS-FLII fusion gene translocation t(11;22)(q24;q12). Multiple repeat metastasectomies, as well as multi-agent chemotherapy and radiotherapy were performed for recurrent disease. Despite treatment, the patient succumbed due to progressive disease 110 months after the initial surgery for gastric ES/PNET. A review of the reported cases suggests that patients with gastric ES/PNETs have an unfavorable prognosis following resection due to the high propensity of these tumors to metastasize. Thus, multimodal treatment approaches including surgery, as well as multi-agent chemotherapy and radiotherapy may provide a survival benefit for patients with gastric ES/PNETs.

DOI： 10.3892/ol.2011.246

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：E-CENTURY PUBLISHING CORP  

This study aimed to evaluate the association between the immunohistochemical expression of NAD(P) H: quinone oxidoreductase-1 (NQO1) and nuclear factor erythroid 2-related factor 2 (Nrf2) in resected specimens of intrahepatic cholangiocarcinoma (ICC) and to elucidate the prognostic value of NQO1 and Nrf2 expression. A retrospective analysis was conducted of 34 consecutive patients who underwent surgical resection for ICC. Immunohistochemistry of the resected specimens was conducted using each of the following primary monoclonal antibodies against NQO1 and Nrf2. Of the 34 patients, 23 were classified as having tumors with NQO1-positive expression and 11 had tumors with loss of NQO1 expression, whereas 22 patients had tumors with Nrf2-positive expression and 12 had tumors with loss of Nrf2 expression. NQO1 expression showed a positive association with Nrf2 expression (p=0.005). Loss of NQO1 expression was more frequent in tumor specimens that were moderately or poorly differentiated (11/26; 42%) than in well-differentiated tumors (0/8; 0%; p=0.034). Post-resection survival was significantly worse in patients with tumors with loss of NQO1 expression than in patients with NQO1-positive tumors (cumulative 5 -year survival rate of 0% and 51%, respectively; p=0.005). Nrf2 expression was not associated with survival after resection (p=0.287). The Cox proportional hazards regression analysis revealed that lymph node involvement (p<0.001) and loss of NQO1 expression (p<0.001) had an independent adverse effect on survival. Loss of NQO1 expression reflects dedifferentiation and thus indicates a poor prognosis for patients undergoing resection for ICC.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

This study was designed to compare the prognostic power of the location of positive lymph nodes with that of the number of positive lymph nodes in gallbladder carcinoma.
A retrospective analysis was conducted of 116 consecutive patients who underwent an R0 radical resection for gallbladder carcinoma. A total of 2,406 lymph nodes taken from the patients were examined histologically. The location of positive regional nodes was classified according to the Japanese staging system. The number of positive regional nodes was recorded for each patient.
Nodal disease was found in 49 patients, of whom 19 survived for more than 5 years after resection. Univariate analysis revealed that both the location (P < 0.0001) and the number (P < 0.0001) of positive nodes were significant prognostic factors. Multivariate analysis revealed that the number of positive nodes was an independent prognostic factor (P < 0.001), whereas the location of positive nodes failed to remain as an independent variable. The cumulative 5-year survival rates were 81% for patients without regional nodal disease, 62% for patients with a single positive node, 43% for patients with 2-3 positive nodes, and 15% for patients with a parts per thousand yen4 positive nodes (P < 0.0001).
The number, not the location, of positive lymph nodes independently determines the prognosis after resection in gallbladder carcinoma. No nodal disease or a single positive node indicates a favorable outcome after resection, whereas radical lymph node dissection is effective for selected patients with multiple positive nodes, provided that an R0 resection is feasible.

DOI： 10.1245/s10434-009-0899-1

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：H G E UPDATE MEDICAL PUBLISHING S A  

Background/Aims: The current study sought to clarify whether intracapsular venous invasion and extratumoral venous invasion confer different prognostic significance in patients undergoing hepatectomy for hepatocellular carcinoma.
Methodology: A retrospective study of 275 consecutive patients who underwent hepatectomy for hepatocellular carcinoma was conducted. Extratumoral venous invasion was defined as gross or microscopic involvement of vessels within the peritumoral liver tissue, whereas intracapsular venous invasion was defined as microscopic involvement of vessels within the fibrous tumor capsule. The median follow-up time was 64 months.
Results: Vascular invasion was found in 104 (38%) of the 275 patients. Intracapsular venous invasion was present in 16 patients and extratumoral venous invasion observed in 88 patients. Overall cumulative survival rates were 64% at 5 years and 45% at 10 years. Vascular invasion was a strong prognostic factor by univariate (p=0.0001) and multivariate (p=0.006) analyses. Survival after hepatectomy was significantly worse in patients with extratumoral venous invasion (cumulative 10-year survival rate of 28%) than in patients with intracapsular venous invasion (cumulative 10-year survival rate of 70%; p=0.0082).
Conclusions: Extratumoral venous invasion adversely influences survival after hepatectomy for hepatocellular carcinoma compared to intracapsular venous invasion.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPANDIDOS PUBL LTD  

We hypothesized that expression Of multidrug resistance-associated protein 2 (MRP2), a major cisplatin transporter, may determine the efficacy of cisplatin as a treatment for patients with hepatocellular carcinoma (HCC). A prospective analysis was conducted of 49 consecutive patients Who underwent resection for HCC (16 patients treated with cisplatin-based neoadjuvant chemotherapy and 33 patients treated without neoadjuvant chemotherapy). Expression of MRP2 in resected specimens was assessed by immunohistochemical and Western blot analyses. The extent of tumor was assessed histologically in the greatest dimension of the tumor specimen from each patient. The median percentage of tumor necrosis was 81% (range: 0-100%) and complete tumor necrosis was found in 3 patients. Over-expression of MRP2 was detected in 24/46 (52%) tumor specimens. In 16 patients treated with overexpression of MRP2 and dose of cisplatin did not correlate With tumor necrosis Of the resected specimens (P=0.706 and P=0.555, respectively). Of 13 tumor specimens containing, vivid tumor from 16 patients treated with cisplatin. 8 had overexpression of MRP2. Tumor specimens with overexpression of MRP2 showed a lower percentage of tumor necrosis than those with non-overexpression (median percentage of tumor necrosis. 19% vs. 99%, P=0.003). In conclusion, overexpression of MRP2 con-elates with I lower percentage of tumor necrosis in patients treated with cisplatin-based neoadjuvant chemotherapy for HCC, whereas either tumor size or dose of cisplatin does not. Exprexssion of MRP2 determines the efficacy cisplatin-based chemotherapy in patients with HCC.

DOI： 10.3892/or_00000721

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

This study aimed to clarify the mode of hepatic spread from gallbladder carcinoma and to elucidate its prognostic value. A retrospective analysis was conducted of 42 consecutive patients who underwent resection for gallbladder carcinoma with hepatic involvement verified histologically. The mode of hepatic spread was classified into 3 patterns: direct invasion through the gallbladder bed, portal tract invasion, and hepatic metastatic nodules. Intrahepatic lymphatic invasion was declared when either single tumor cells or cell clusters were clearly visible within vessels that showed immunoreactivity to the D2-40 monoclonal antibody. Seven, 24, and 11 patients had direct invasion alone, portal tract invasion with (22 patients) or without (2 patients) direct invasion, and hepatic metastatic nodules, respectively. Of the 24 patients with portal tract invasion, 14 had intrahepatic lymphatic invasion, 8 had neither intrahepatic lymphatic nor venous invasion, and 2 had both intrahepatic lymphatic and venous invasion. To date, 4 patients with direct invasion alone and 4 patients with portal tract invasion survived more than 5 years after resection, whereas all the patients with hepatic metastatic nodules died within 11 months after resection, irrespective of the type of hepatectomy. The mode of hepatic spread (P < 0.001) was a strong independent prognostic factor. Direct liver invasion and portal tract invasion, which features intrahepatic lymphatic invasion, are the main modes of hepatic spread from resectable gallbladder carcinoma. The mode of hepatic spread independently predicts long-term Survival after resection for patients with gallbladder carcinoma. Hepatic metastatic nodules indicate a dismal outcome after resection.

DOI： 10.1097/PAS.0b013e3181c467d4

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

BACKGROUND: We tested the hypothesis that in patients with T1 extrahepatic cholangiocarcinoma (EHC), prognosis postresection is significantly different for those with tumors that are limited to the mucosa than for those with tumors that have invaded (but not penetrated) the fibromuscular layer. METHODS: A retrospective analysis was conducted of 33 consecutive patients with pathologic T1 (pT1) EHC tumors. According to the depth of invasion, the pT1 tumors were divided into 2 groups: Group 1, tumors that were limited to the mucosa (mucosal tumors); and Group 2, tumors that had invaded (but not penetrated) the fibromuscular layer (fibromuscular layer-invasive tumors). Longterm outcomes after resection were compared between the 2 groups for a median follow-up time of 175 months. RESULTS: Eighteen patients had mucosal tumors and 15 patients had tumors that had invaded the fibromuscular layer. None of the patients with mucosal tumors had lymphovascular invasion, whereas 3 of the patients with fibromuscular layer-invasive tumors had lymphovascular invasion (P = .083). Overall survival after resection was better in Group 1 than in Group 2 (cumulative 10-year survival rate, 100% vs 52%; P = .024). The rate of disease-free survival after resection was higher in Group 1 than in Group 2 (cumulative disease-free 10-year survival rate, 100% vs 56%; P = .022). CONCLUSIONS: The long-term outcome after resection for EHC is significantly better for patients with mucosal tumors than for patients with fibromuscular layer-invasive tumors. This suggests that the depth of tumor invasion affects the postresection prognosis for patients with pT1 EHC. Cancer 2010;116:400-5. (C) 2070 American Cancer Society.

DOI： 10.1002/cncr.24766

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

This study evaluated the impact of ductal bile bacteria (bactibilia or cholangitis) on the development of surgical site infection (SSI) or in-hospital mortality after resection for hilar cholangiocarcinoma.
A retrospective analysis was conducted on 81 patients who underwent a combined major hepatic (hemihepatectomy or more extensive hepatectomy) and bile duct resection for hilar cholangiocarcinoma. Ductal bile was submitted for bacterial culture before or during the operation.
The incidence of SSI was higher in patients with preoperative bactibilia (83%) than in patients without (52%; P = 0.008). Preoperative bactibilia was an independent variable associated with SSI (relative risk 9.003; P = 0.002). The incidence of in-hospital mortality was higher in patients with preoperative cholangitis (33%) than in patients without (6%; P = 0.009). Preoperative cholangitis was the only independent variable associated with in-hospital mortality (relative risk 9.115; P = 0.006).
Preoperative cholangitis independently increases in-hospital mortality after combined major hepatic and bile duct resection for hilar cholangiocarcinoma, whereas preoperative bactibilia independently increases SSI.

DOI： 10.1007/s00423-009-0464-1

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER TOKYO  

Information concerning the pulmonary toxicity of oxaliplatin with infusional 5-fluorouracil plus leucovorin (FOLFOX) is very limited. We herein report the case of a patient with FOLFOX-induced interstitial pneumonia. An 82-year-old man with unresectable colon cancer liver metastases was referred to our department for chemotherapy with the FOLFOX protocol. After the administration of ten cycles, he visited our outpatient clinic with a 2-week history of coughing and shortness of breath; he was afebrile. A chest radiograph showed reticular shadows with ground-glass opacities mainly involving the middle and lower zones of the right lung. Computed tomography depicted ground-glass opacities with superimposed reticulation in the right lung. A diagnosis of FOLFOX-induced interstitial pneumonia was made based on the clinical course and imaging findings. The symptoms disappeared within 3 days after the cessation of the FOLFOX regimen and the initiation of high-dose corticosteroid treatment. Two months after the initiation of the corticosteroid treatment, complete remission of the radiological abnormalities was confirmed; thereafter, interstitial pneumonia did not recur despite the reintroduction of 5-fluorouracil/leucovorin alone, suggesting that 5-fluorouracil/leucovorin alone was not responsible for the development of the interstitial pneumonia. Thus, oxaliplatin, alone or in combination with 5-fluorouracil/leucovorin, may have caused the interstitial pneumonia in this patient. Once interstitial pneumonia has occurred, cessation of the regimen is mandatory, and high-dose corticosteroid treatment is commonly given to rescue patients from this potentially lethal complication.

DOI： 10.1007/s10147-008-0863-2

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.4254/wjh.v1.i1.103

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：H G E UPDATE MEDICAL PUBLISHING S A  

Background/Aims: This retrospective study aimed to define the role of hepatic lymph node dissection in the surgical management of patients with resectable colorectal carcinoma liver metastases.
Methodology: Fourteen of the 130 consecutive patients who had hepatectomy for colorectal carcinoma liver metastases underwent concomitant hepatic lymph node dissection for nodal disease suspected during the operation. A total of 125 hepatic lymph nodes (median, 8 per patient) were examined histologically for metastases. The therapeutic value index of hepatic lymph node dissection was estimated by multiplying the incidence of hepatic lymph node metastasis by the 5-year survival rate of patients with hepatic lymph node metastasis. The median follow-up time was 98 months.
Results: Mortality occurred within 30 days after resection in 1 patient. Hepatic lymph node metastases were detected in 7 patients, of whom 2 with no residual tumor survived for 10 years. The incidence and 5-year survival rate for patients with hepatic lymph node metastases were 50% and 29%, respectively. The therapeutic value index of hepatic lymph node dissection was 14.5.
Conclusions: Hepatic lymph node dissection provides a survival benefit for some patients with hepatic nodal disease of resectable colorectal carcinoma liver metastases, provided that a potentially curative (R0) resection is feasible.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：W B SAUNDERS CO-ELSEVIER INC  

This Study retrospectively evaluated the immunohistochemical expression of 3 cell adhesion molecules (CAMs), E-cadherin, beta-catenin, and osteopontin, according to tumor grade in 125 surgically resected specimens of hepatocellular carcinoma (HCC). The aims of this study were to identify factors associated with vascular invasion and to elucidate the prognostic value of CAMs. The median follow-up time was 110 months. The levels of E-cadherin, beta-catenin, and osteopontin osteopontin immunoreactivity were significantly associated with Edmondson-Steiner grade but not With tumor size. There Was increased loss of E-cadherin, nonnuclear overexpression of beta-catenin, and overexpression of osteopontin in tumors of higher histologic grade. Vascular invasion was found in 44 (35%) of 125 resected specimens. Logistic regression analysis identified 3 tumor-related factors that were independently associated with vascular invasion-tumor size more than 3 cm, Edmondson-Steiner grades III to IV and overexpression of osteopontin. Among the tested CAMs, osteopontin (P=.0110) and E-cadherin (P=.0287) were significant prognostic factors by univariate analysis. The Cox proportional hazard regression analysis revealed that Edmondson-Steiner grades III to IV (relative risk [RR], 3.028; P <.001), the presence of vascular invasion (RR, 1.964: P .011), overexpression of osteopontin (RR, 1.755; P=.034), serum alpha-fetoprotein level more than 20 ng/mL (RR, 1.834: P =.037), and Child-Pugh classification B to C (RR, 1.880; P =.040) were found to be independently significant factors associated with Survival after hepatectomy. These results suggest that overexpression of osteopontin independently correlates with vascular invasion and thus predicts poor survival for patients with HCC, whereas aberrant expression of E-cadherin or beta-catenin does not. (C) 2008 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.humpath.2008.05.006

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

Background: This study sought to clarify the distribution of intrahepatic micrometastases and elucidate an adequate hepatectomy margin for colorectal carcinoma liver metastases.
Methods: Intrahepatic micrometastases in resected specimens from 90 patients who underwent hepatectomy for colorectal carcinoma liver metastases were examined retrospectively. Intrahepatic micrometastases were defined as microscopic lesions spatially separated from the gross tumor. Distances from these lesions to the hepatic tumor borders were measured histologically, and the density of intrahepatic micrometastases (number of lesions/mm(2)) calculated relative to the advancing tumor border in a zone < 1 cm from the border (close) or >= 1 cm away (distant). Median follow-up time was 127 months.
Results: A total of 294 intrahepatic micrometastases were detected in 52 (58%) patients; 95% of these occurred in the close zone. The density of intrahepatic micrometastases was significantly higher in the close zone (mean 74.8 x 10(-4) lesions/mm(2)) than in the distant zone (mean 7.4 x 10(-4) lesions/mm(2); P < 0.001). Hepatectomy margin status was positive by 0 cm in 10 patients or negative by < 1 cm in 51, and by >= 1 cm in 29 patients. The median survival times were 18, 33, and 89 months in patients with hepatectomy margins 0 cm, < 1 cm, and >= 1 cm, respectively. Hepatectomy margin status independently influenced survival (P < 0.001) and disease-free survival (P < 0.001).
Conclusion: The currently recommended >= 1 cm hepatectomy margin should remain the goal for resections of colorectal carcinoma liver metastases, based on the distribution of intrahepatic micrometastases and survival risk.

DOI： 10.1245/s10434-008-0023-y

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCI LTD  

Aims: Intrahepatic recurrence is the most common manifestation of failure after local ablation therapy for hepatocellular carcinoma. The present study evaluates the safety and efficacy of partial hepatectomy for intrahepatic recurrence after prior local ablation.
Methods: A retrospective analysis was conducted of 188 consecutive patients with hepatocellular carcinoma who underwent either partial hepatectomy for recurrence after prior local ablation (n = 13) or partial hepatectomy as initial local treatment (n = 175). The 13 patients with recurrence after prior local ablation were referred to our division after the resectable recurrences were considered to be resistant to non-surgical treatment modalities.
Results: The incidences of postoperative morbidity and mortality were similar for patients with prior local ablation and patients without prior local ablation (p = 0.75 and p = 0.52, respectively). The overall survival rates after hepatectomy were comparable between patients with prior local ablation (median survival time of 86 months; cumulative 5-year survival rate of 63%) and patients without prior local ablation (median survival time of 76 months; cumulative 5-year survival rate of 54%; p = 0.60). The disease-free survival rates after hepatectomy were significantly worse for patients with prior local ablation based on both univariate (p = 0.01) and multivariate (relative risk, 2.73; p < 0.01) analyses.
Conclusions: Hepatectomy can be performed safely and may be efficacious, in terms of overall survival, for selected patients with intrahepatic recurrence after prior local ablation for hepatocellular carcinoma. On the other hand, prior local ablation appears to increase the probability of failure after hepatectomy. (C) 2007 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.ejso.2007.03.018

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.ejso.2008.01.031

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

Background: D2-40 monoclonal antibody immunoreactivity is specific for lymphatic endothelium and therefore provides a marker of lymphatic invasion. We hypothesized that intrahepatic lymphatic invasion reflects the nodal status of colorectal carcinoma liver metastases and may function as an adverse prognostic factor.
Methods: A retrospective analysis of 105 consecutive patients who underwent resection for colorectal carcinoma liver metastases was conducted. Intrahepatic lymphatic invasion was declared when either single tumor cells or cell clusters were clearly visible within vessels that showed immunoreactivity for D2-40 monoclonal antibody. The median follow-up time was 124 months.
Results: Of 105 patients, 13 were classified as having intrahepatic lymphatic invasion. All tumor foci of intrahepatic lymphatic invasion were detected within the portal tracts. Intrahepatic lymphatic invasion was significantly associated with hepatic lymph node involvement (P = 0.039). Survival after resection was significantly worse in patients with intrahepatic lymphatic invasion (median survival time of 13 months; cumulative five-year survival rate of 0%) than in patients without (median survival time of 40 months; cumulative five-year survival rate of 41%; P < 0.0001). Patients with intrahepatic lymphatic invasion also showed decreased disease-free survival rates (P < 0.0001). Intrahepatic lymphatic invasion thus independently affected both survival (relative risk, 7.666; 95% confidence interval, 3.732-15.748; P < 0.001) and disease-free survival (relative risk, 4.112; 95% confidence interval, 2.185-7.738; P < 0.001).
Conclusions: Intrahepatic lymphatic invasion is associated with hepatic lymph node involvement and is an adverse prognostic factor in patients with colorectal carcinoma liver metastases.

DOI： 10.1245/s10434-007-9594-2

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：W J G PRESS  

AIM: To clarify whether perimuscular connective tissue contains more lymphatic vessels than the shallower layers in human gallbladders.
METHODS: Lymphatic vessels were stained immunohistochernically with monoclonal antibody D2-40, which is a specific marker of lymphatic endothelium, 'in representative sections of 12 normal human gallbladders obtained at the time of resection for colorectal carcinoma liver metastases. In individual gallbladder specimens, nine high-power (x 200) fields with the highest lymphatic vessel density (LVD), termed "hot spots", were identified for each layer (mucosa, muscle layer, and perimuscular connective tissue). In individual hot spots, the LVD and relative lymphatic vessel area (LVA) were measured microscopically using a computer-aided image analysis system. The mean LVD and LVA values for the nine hot spots in each layer were used for statistical analyses.
RESULTS: In the mucosa, muscle layer, and perimuscular connective tissue, the LVD was 16.1 +/- 9.2 , 35.4 +/- 15.7, and 65.5 +/- 12.2, respectively, and the LVA was 0.4 +/- 0.4, 2.1 +/- 1.1, and 9.4 +/- 2.6, respectively. Thus, both the LVD and LVA differed significantly (P < 0.001 and P < 0.001, respectively; Kruskal-Wallis test) among the individual layers of the wall of the gallbladder, with the highest LVD and LVA values in the perimuscular connective tissue. Most (98 of 108) of the hot spots within the perimuscular connective tissue were located within 500 pm of the lower border of the muscle layer.
CONCLUSION: The perimuscular connective tissue contains more and larger lymphatic vessels than the shallower layers in the human gallbladder. This observation partly explains why the incidence of lymph node metastasis is high in T2 (tumor invading the perimuscular connective tissue) or more advanced gallbladder carcinoma. (c) 2007 WJG. All rights reserved.

DOI： 10.3748/wjg.v13.i33.4480

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

Background: This study aimed to evaluate the effect of anatomic resection on long-term outcomes in patients with pathologic T1-T2 (pT1-T2) hepatocellular carcinoma.
Methods: A retrospective analysis of 158 consecutive patients who underwent either anatomic (n = 95) or nonanatomic (n = 63) resection for pT1-T2 hepatocellular carcinoma was conducted. Anatomic resection was defined as the complete removal of at least one Couinaud segment containing the tumor; nonanatomic resection was defined as removal of the tumor plus a rim of nonneoplastic liver parenchyma. The median follow-up time was 83 months.
Results: Patients who underwent anatomic resection were characterized by lower prevalence of cirrhosis (P = .015), more favorable hepatic function (P = .001), larger tumor size (P = .029), and higher prevalence of vascular invasion (P = .008) compared with patients who underwent nonanatomic resection. Anatomic resection provided better survival (median survival time, 122 months) than nonanatomic resection (median survival time, 76 months; P = .0358). Patients who underwent anatomic resection had better disease-free survival (P = .0121). Anatomic resection independently improved both survival (hazard ratio, .46; P = .003) and disease-free survival (hazard ratio, .55; P = .008). When stratified for pT classification, the effectiveness of anatomic resection remained only in patients with pT2 tumors in terms of survival (P = .0012) and disease-free survival (P = .0004).
Conclusions: Anatomic resection independently improves long-term survival in patients with T1-T2 hepatocellular carcinoma, probably because of the clearance of venous tumor thrombi within the resected domain.

DOI： 10.1245/s10434-006-9318-z

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.ejso.2006.10.008

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

Background: This study aimed to clarify the clinical significance of lymph node micrometastasis in ampullary carcinoma.
Materials and Methods: Pancreaticoduodenectomy with regional lymphadenectomy was performed for 50 consecutive patients with ampullary carcinoma. A total of 1,283 regional lymph nodes (median, 25 per patient) were examined histologically for metastases. Overt metastasis was defined as metastasis detected during routine histologic examination with hematoxylin and eosin. Micrometastasis was defined as metastasis first detected by immunohistochemistry with an antibody against cytokeratins 7 and 8. The median follow-up period was 119 months after resection.
Results: Overt metastasis was positive in 90 lymph nodes from 27 patients. Micrometastasis was positive in 33 lymph nodes from 12 patients, all of whom also had overt nodal metastases. Patients with nodal micrometastasis had a larger number of lymph nodes with overt metastasis (median, 3.5) than those without (median, 0; P < 0.001). Overt metastasis to distant nodes (superior mesenteric nodes, para-aortic nodes) was more frequent (P = 0.001 and P = 0.038, respectively) in patients with nodal micrometastasis. Nodal micrometastasis was found to be a strong independent prognostic factor on univariate (P < 0.0001) and multivariate (relative risk, 5.085; P = 0.007) analyses. From among the 27 patients with overt nodal metastasis, the outcome after resection was significantly worse in the patients with nodal micrometastasis (median survival time of 11 months) than in those without (median survival time of 63 months; P = 0.0009).
Conclusions: Immunohistochemically detected lymph node micrometastasis indicates intensive lymphatic spread, and thus adversely affects the survival of patients with ampullary carcinoma.

DOI： 10.1007/s00268-005-7985-8

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：W J G PRESS  

AIM: To determine which treatment modality hepatectomy or percutaneous ablation - is more beneficial for patients with small hepatocellular carcinoma (HCC) (<= 4 cm) in terms of long-term outcomes.
METHODS: A retrospective analysis of 149 patients with HCC <= 4 cm was conducted. Eighty-five patients underwent partial hepatectomy (anatomic in 47 and non-anatomic in 38) and 64 underwent percutaneous ablation (percutaneous ethanol injection in 37, radiofrequency ablation in 21, and microwave coagulation in 6). The median follow-up period was 69 mo.
RESULTS: Hepatectomy was associated with larger tumor size (P<0.001), whereas percutaneous ablation was significantly associated with impaired hepatic functional reserve. Local recurrence was less frequent following hepatectomy (P<0.0001). Survival was better following hepatectomy (median survival time: 122 mo) than following percutaneous ablation (median survival time: 66 mo; P = 0.0123). When tumor size was divided into <= 2 cm vs > 2 cm, the favorable effects of hepatectomy on long-term survival was seen only in patients with tumors >2 cm (P=0.0001). The Cox proportional hazards regression model revealed that hepatectomy (P=0.006) and tumors <= 2 cm (P=0.017) were independently associated with better survival.
CONCLUSION: Hepatectomy provides both better local control and better long-term survival for patients with HCC <= 4 cm compared with percutaneous ablation. Of the patients with HCC <= 4 cm, those with tumors > 2 cm are good candidates for hepatectomy, provided that the hepatic functional reserve of the patient permits resection. (C) 2006 The WJG Press. All rights reserved.

DOI： 10.3748/wjg.v12.i4.546

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BAISHIDENG PUBL GRP CO LTD  

AIM: To estimate the incidence of catheter tract implantation metastasis among patients undergoing percutaneous transhepatic biliary drainage (PTBD) for extrahepatic cholangiocarcinoma, and to provide data regarding the management of this unusual complication of PTBD by reviewing cases reported in the literature.
METHODS: A retrospective analysis of 67 consecutive patients who underwent PTBD before the resection of extrahepatic cholangiocarcinoma was conducted. The median follow-up period after PTBD was 106 mo. The English language literature (PubMed, National Library of Medicine, Bethesda, MD, USA), from January 1966 through December 2004, was reviewed.
RESULTS: Catheter tract implantation metastasis developed in three patients. The cumulative incidence of implantation metastasis reached a plateau (6%) at 20 mo after PTBD. All of the three patients with implantation metastasis died of tumor progression at 3, 9, and 20 mo after the detection of this complication. Among the 10 reported patients with catheter tract implantation metastasis from extrahepatic cholangiocarcinoma (including our three patients), two survived for more than 5 years after the excision of isolated catheter tract metastases.
CONCLUSION: Catheter tract implantation metastasis is not a rare complication following PTBD for extrahepatic cholangiocarcinoma. Although the prognosis for patients with this complication is generally poor, the excision of the catheter tract may enable survival in selected patients with isolated metastases along the catheter tract. (C) 2005 The WJG Press and Elsevier Inc. All rights reserved.

DOI： 10.3748/wjg.v11.i44.7024

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BAISHIDENG PUBL GRP CO LTD  

AIM: To clarify the pathogenesis of biliary dilatation associated with anomalous union of the pancreatic and biliary ducts (AUPBD).
METHODS: Direct cholangiopancreatograms of 350 adult patients with or with suspicion of hepatobiliary or pancreatic disorders were reviewed. AUPBD was diagnosed cholangiopancreatographically, when the pancreaticobiliary ductal union was located above the narrow distal segment of the bile duct, which represents the action of the sphincter of Oddi. The narrow portion of the terminal choledochus was defined as symmetrical stricture of the common bile duct just above the pancreaticobiliary ductal union.
RESULTS: AUPBD was found in 36 patients. Among cholangiopancreatographic features, the narrow portion of the terminal choledochus was the most pathognomonic for AUPBD (accuracy, 98%); it was present in 29 (81%) patients with AUPBD, but was not found in any patients without AUPBD. Among patients with AUPBD, biliary dilatation (>10 mm) was more frequent in those with the narrow portion of the terminal choledochus (23/29) than in those without (2/7; P = 0.018) AUPBD. Among the patients with both AUPBD and the narrow portion of the terminal choledochus, there was a strong negative correlation between the minimum diameter of the narrow portion and the maximum diameter of the choledochus (r = -0.78, P < 0.001), suggesting that the degree of biliary narrowing at the narrow portion correlates with that of upstream biliary dilatation.
CONCLUSION: The narrow portion of the terminal choledochus, a pathognomonic radiologic feature of AUPBD, may be a cause of biliary dilatation in patients with AUPBD. (C) 2005 The WJG Press and Elsevier Inc. All rights reserved.

DOI： 10.3748/wjg.v11.i41.6503

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

Humoral hypercalcemia can arise from a variety of malignancies, but its association with primary colorectal carcinoma is rare, with only 20 such cases documented in the English-language literature to date. We report an additional case to clarify the clinicopathologic features of colorectal carcinoma with humoral hypercalcemia. A 54-year-old woman was admitted with symptomatic hypercalcemia of 14.2 mg/dl and multiple hepatic metastases, 2 years after resection of sigmoid colon cancer. The hypercalcemia was caused by the circulating parathyroid hormone-related peptide (PTHrP) produced by poorly differentiated adenocarcinoma in the liver. The PTHrP level on admission was 13.5 pmol/l. Despite systemic chemotherapy, the patient died of disease progression 3 weeks after the humoral hypercalcemia was diagnosed. A review of the 21 reported cases, including ours, suggests that colorectal carcinoma associated with humoral hypercalcemia is characterized by a poorly differentiated tumor with or without squamous or neuroendocrine features, distant metastases, and a dismal prognosis.

DOI： 10.1007/s00595-004-2974-3

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：OXFORD UNIV PRESS  

Mouse thymic lymphomas induced by gamma-irradiation exhibited homozygous deletions of the Rit1/Bcl11b tumor suppressor gene on chromosome 12 at high frequencies. Internal deletions of one allele were frequently accompanied by loss of the other allele. In order to elucidate the mechanism of these internal deletions, the sites of breakage and rejoining were examined by PCR mapping and sequencing. The 5' site of the deletions clustered within an similar to5 kb region of intron 1 and the 3' site was confined to a site in intron 3. These sites contained P and/or N nucleotides and cryptic sequences recognizable by the RAG1/2 recombinase in the vicinity. This suggests that the Rit1 intragenic deletions were generated by endogenous illegitimate V(D)J recombinase activity and such aberrant recombination was also detected by nested PCR of DNA from the thymus of unirradiated mice but not of RAG2-deficient mice. A rough estimate indicated that there reside as many as 10(3)-10(4) thymocytes having Rit1 deletions, assuming the presence of 10(8) thymocytes in the thymus of unirradiated mice. Moreover, the recombination frequency was not affected by gamma-irradiation. These results show no effect of radiation on Rit1 mutations and suggest an indirect mechanism for its role in lymphomagenesis.

DOI： 10.1093/carcin/bgh094

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：NATURE PUBLISHING GROUP  

The gene Bcl11b, which encodes zinc finger proteins, and its paralog, Bcl11a, are associated with immune-system malignancies. We have generated Bcl11b-deficient mice that show a block at the CD4(-)CD8(-) double-negative stage of thymocyte development without any impairment in cells of B- or gammadelta T cell lineages. The Bcl11b(-/-) thymocytes showed unsuccessful recombination of V-beta to D-beta and lacked the pre-T cell receptor (TCR) complex on the cell surface, owing to the absence of Tcrb mRNA expression. In addition, we saw profound apoptosis in the thymus of neonatal Bcl11b(-/-) mice. These results suggest that Bcl11b is a key regulator of both differentiation and survival during thymocyte development.

DOI： 10.1038/ni927

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