Pancreatic cancer arising from the remnant pancreas after pancreatectomy: a multicenter retrospective study by the Kyushu Study Group of Clinical Cancer.

BACKGROUND: After initial pancreatic resection, local recurrence of pancreatic cancer (PC) or new primary PC can develop in the remnant. There are limited data available regarding this so-called remnant PC. The aim of this retrospective study was to clarify the clinical features and establish a treatment strategy for remnant PC. METHODS: A multicenter retrospective study with the Kyushu Study Group of Clinical Cancer was carried out. Clinical data from 50 patients who developed remnant PC were analyzed. RAS mutation analysis of the initial tumor and of remnant PC was performed in 17 cases. RESULTS: The initial pancreatic resections were performed for 37 invasive ductal carcinomas, and for 13 other tumors. Thirty-seven patients underwent a second pancreatectomy for remnant PC (resected group), while thirteen patients were not operated (unresected group). The median overall survival times were 42.2 months in the resected group and 12.3 months in the unresected group (HR 0.374; 95% CI 0.17-0.83). In RAS mutation analysis, 14 cases had at least 1 missense variant of KRAS, HRAS, or NRAS in the initial pancreatic tumor and/or remnant PC. The same missense variants between the initial tumor and remnant PC were discovered only in KRAS of one patient, and in HRAS of one patient. No case had completely consistent missense variants between the initial tumor and remnant PC. CONCLUSIONS: This study found that repeated pancreatectomy for remnant PC can prolong patient survival, and RAS mutation analysis indicated that many remnant PCs are developed from metachronous multifocal origins.

Validation of an assessment tool: Estimation of Postoperative Overall Survival for Gastric Cancer.

BACKGROUND: Benchmarking of long-term surgical outcomes has rarely been attempted. We previously devised a prediction model for assessing the outcome of late survival after surgery, termed the Estimation of Postoperative Overall Survival for Gastric Cancer (EPOS-GC). This study was undertaken to validate EPOS-GC in an external data set. METHODS: A retrospective cohort study was conducted in 11 cancer care hospitals in Japan, analyzing a consecutive series of patients who underwent elective gastric cancer resection between April 2007 and March 2009. EPOS-GC consists of three tumor-related variables and three physiological variables. The primary endpoint was postoperative overall survival. The observed-to-expected (O/E) ratio of 5-year survival rates was defined as a metric of quality of care. The sample size for O/E was determined as 42. RESULTS: We included 2045 patients for analysis. The median (95% confidence interval) follow-up time was 5.1 (1.2-6.8) years for censored patients. Although EPOS-GC demonstrated a good discriminative power (Harrell's C-index, 95% confidence interval: 0.80, 0.79-0.83), the calibration plot revealed that EPOS-GC underestimated 5-year survival rates in the high-risk group. Therefore, we recalibrated the model with Cox's regression analysis. The recalibrated EPOS-GC showed a good calibration, preserving the high discriminative power (C-index, 95% confidence interval: 0.80, 0.78-0.82). The O/E among hospitals according to the recalibrated EPOS-GC ranged between 0.87 and 1.27. The O/E correlated with hospital volumes (Spearman's correlation = 0.76, n = 11, p = .006). CONCLUSION: EPOS-GC with recalibration can convey risk-adjusted quality assurance regarding late survival following gastric cancer resection.

A case report of primary neuroendocrine carcinoma of the perihilar bile duct.

BACKGROUND: Although neuroendocrine tumors are most commonly found in the digestive system, neuroendocrine tumors originating from the bile duct are rare, and neuroendocrine carcinomas derived from the perihilar bile duct are extremely rare. This report presents the clinical course and clinicopathological features of neuroendocrine carcinomas arising from the extrahepatic bile duct. CASE PRESENTATION: A 70-year-old Japanese woman was preoperatively diagnosed with perihilar cholangiocarcinoma, and a radical resection with an extended left hepatic lobectomy and a choledochojejunostomy was performed. From the histopathological findings, we diagnosed the tumor as a neuroendocrine carcinoma of the bile duct (small cell type) with lymph node metastasis. The patient was treated with the same adjuvant chemotherapy as that used for small cell carcinoma of the lung. At 10 months after surgery, there was no recurrence of the disease. CONCLUSION: Neuroendocrine carcinoma of the extrahepatic biliary tracts is a very rare and highly malignant disease with a poor prognosis. A multidisciplinary approach could improve the prognosis for this neoplasm.

Changes in expression levels of ERCC1, DPYD, and VEGFA mRNA after first-line chemotherapy of metastatic colorectal cancer: results of a multicenter study.

Our previous study showed that administering oxaliplatin as first-line chemotherapy increased ERCC1 and DPD levels in liver colorectal cancers (CRCs) metastases. Second, whether the anti-VEGF monoclonal antibody bevacizumab alters tumoral VEGFA levels is unknown. We conducted this multicenter observational study to validate our previous findings on ERCC1 and DPD, and clarify the response of VEGFA expression to bavacizumab administration. 346 CRC patients with liver metastases were enrolled at 22 Japanese institutes. Resected liver metastases were available for 175 patients previously treated with oxaliplatin-based chemotherapy (chemotherapy group) and 171 receiving no previous chemotherapy (non-chemotherapy group). ERCC1, DPYD, and VEGFA mRNA levels were measured by real-time RT-PCR. ERCC1 mRNA expression was significantly higher in the chemotherapy group than in the non-chemotherapy group (P = 0.033), and were significantly correlated (Spearman's correlation coefficient = 0.42; P < 0.0001). VEGFA expression level was higher in patients receiving bevacizumab (n = 51) than in those who did not (n = 251) (P = 0.007). This study confirmed that first-line oxaliplatin-based chemotherapy increases ERCC1 and DPYD expression levels, potentially enhancing chemosensitivity to subsequent therapy. We also found that bevacizumab induces VEGFA expression in tumor cells, suggesting a biologic rationale for extending bevacizumab treatment beyond first progression.

Surgical treatment of pT2 gallbladder carcinoma: a reevaluation of the therapeutic effect of hepatectomy and extrahepatic bile duct resection based on the long-term outcome.

BACKGROUND: The clinical indications for hepatectomy and extrahepatic bile duct resection (EBDR) for pT2 gallbladder carcinoma (GBC) remains controversial. The aim of this study is to elucidate the therapeutic effect of hepatectomy and extrahepatic bile duct resection on the surgical treatment of pT2 GBC. METHODS: Ninety-four patients with pT2 GBC who underwent a potentially curative resection were retrospectively analyzed regarding their pathological findings, surgical procedures, and survival. RESULTS: The most powerful predicting factor for the survival is the nodal status. The 5-year survival rate was 87.1% for the pN0 patients and 55.7% for the pN1 patients. With respect to surgical procedures, the 5-year survival rate was 73.3% for the 51 patients with hepatectomy, and 87.2% for the 43 patients without hepatectomy. In addition, the 5-year survival rate was 66.7% for the 11 patients with EBDR, and 81.1% for the 83 patients without EBDR. When restricting the patients to those with pN1 disease, the 5-year survival rate of the patients who received these procedures did not surpass that of the patients who did not. CONCLUSION: There is no positive therapeutic effect besides providing surgical margins in hepatectomy and EBDR in the surgical treatment of pT2 GBC whereas lymph node dissection is most effective procedure for improving survival. Provided that the negative surgical margins are secured, a hepatectomy and an EBDR can therefore be withheld in the surgical treatment for the pT2 GBC.