Yasuo Hayashidani

Adjuvant Gemcitabine Plus S-1 Chemotherapy Improves Survival After Aggressive Surgical Resection for Advanced Biliary Carcinoma

Objective:The aim of this study was to evaluate the efficacy of adjuvant gemcitabine plus S-1 chemotherapy after aggressive surgical resection for advanced biliary carcinoma. Summary Background Data:No effective adjuvant therapy for advanced biliary carcinoma has been reported although its prognosis is extremely poor. Methods:Medical records were reviewed for 103 patients with International Union Against Cancer (UICC) stage II biliary carcinoma who underwent aggressive surgical resection. About 50 patients received 10 cycles of adjuvant gemcitabine plus S-1 chemotherapy and 53 patients did not. Clinicopathological factors and patient survival were compared between the 2 groups using univariate and multivariate analysis. A cycle of chemotherapy consisted of intravenous gemcitabine 700 mg/m2 on day 1 and oral S-1 50 mg/m2 for 7 consecutive days, followed by a 1-week break from chemotherapy. Results:Patient demographics, tumor characteristics, and surgical procedures did not differ between the 2 groups. Aggressive surgical procedures including major hepatectomy or pancreatoduodenectomy were performed for 94 of 103 patients. In the chemotherapy group, 37 patients (74%) were given the full number of 10 cycles. The use of postoperative adjuvant chemotherapy (P < 0.001) and surgical margin status (P = 0.003) were independently associated with long-term survival by multivariate analysis. Five-year survival rates of patients who did or did not receive postoperative adjuvant chemotherapy were 57% and 24%, respectively (P < 0.001). Toxicity during chemotherapy was mild. Conclusions:Adjuvant gemcitabine plus S-1 chemotherapy may be one of several factors contributing to improved outcomes after aggressive surgical resection of advanced biliary carcinoma in recent years.

Number of Metastatic Lymph Nodes, but Not Lymph Node Ratio, Is an Independent Prognostic Factor after Resection of Pancreatic Carcinoma

BACKGROUND This study evaluated the prognostic significance of the number of metastatic lymph nodes and the ratio of metastatic nodes to total number of examined lymph nodes (lymph node ratio, LNR) after resection of pancreatic carcinoma. STUDY DESIGN Records of 119 consecutive patients with pancreatic ductal carcinoma, who underwent R0 or R1 pancreatectomy with regional node dissection, were reviewed retrospectively. Clinical factors, pathologic factors including number of metastatic nodes and LNR, and survival were analyzed by univariate and multivariate analyses. RESULTS Overall survival rates were 78%, 28%, and 20% at 1, 3, and 5 years, respectively. The median numbers of evaluated lymph nodes and involved nodes were 28 and 3, respectively. Univariate analysis revealed that tumor location, postoperative adjuvant chemotherapy, tumor differentiation, choledochal invasion, portal or splenic vein invasion, extrapancreatic nerve plexus invasion, resection margin status, node status, number of involved nodes, LNR, International Union against Cancer (UICC) pT factor, and UICC stage correlated significantly (p < 0.05) with increased survival. By multivariate analysis, negative node metastasis (p = 0.008) and 0 or 1 involved node (p = 0.004), but not LNR, correlated independently with longer survival. The 1-, 3-, and 5-year survival rates of patients with 0 or 1 metastatic node and patients with 2 or more metastatic nodes were 91%, 48%, and 40% and 66%, 10%, and 0%, respectively. CONCLUSIONS The number of metastatic nodes, but not LNR, is one of the most powerful prognostic factors after resection of pancreatic carcinoma.

Pancreatoduodenectomy for Distal Cholangiocarcinoma: Prognostic Impact of Lymph Node Metastasis

BackgroundThe aim of this study was to identify useful prognostic factors in patients undergoing pancreatoduodenectomy for distal cholangiocarcinoma.MethodsThe records of 36 patients with distal cholangiocarcinoma undergoing pancreatoduodenectomy were retrospectively reviewed. Potential clinicopathological prognostic factors that may affect survival were examined by univariate and multivariate analysis.ResultsThere was no mortality. Overall survival rates were 75%, 54%, and 50% for 1, 3 and 5 years, respectively (median survival time, 26 months). Univariate analysis found that age (≧ 65 years), pancreatic invasion, duodenal invasion, lymph node metastasis, perineural invasion and a positive surgical margin were significant predictors of poor prognosis (P < 0.05). Furthermore, lymph node metastasis was found to be a significant independent predictor of poor prognosis by multivariate analysis (P = 0.043). Moreover, there were significant differences in the 5-year survival between patients with 2 or less involved lymph nodes and those with 3 or more positive nodes (P < 0.001). There were no 2-year survivors of the group of patients with 3 or more positive nodes.ConclusionsThese results suggest that the presence and number of lymph nodes exhibiting metastatic disease might be useful in predicting the postsurgical outcome in patients undergoing pancreatoduodenectomy for distal cholangiocarcinoma.

An Antecolic Roux-en Y type Reconstruction Decreased Delayed Gastric Emptying after Pylorus-Preserving Pancreatoduodenectomy

The aim of this study was to identify a preferable procedure reducing the incidence of delayed gastric emptying (DGE) after pylorus-preserving pancreatoduodenectomy (PPPD). Data on 132 consecutive patients with pancreatobiliary disease, who underwent PPPD, were collected retrospectively. A retrocolic Billroth I type reconstruction (B-I group) and an antecolic Roux-en Y type reconstruction (R-Y group) were performed for 54 and 78 patients after PPPD, respectively. Clinical measures of DGE were compared between the two groups. The incidence of DGE was 81% in B-I group and 10% in R-Y group (P < 0.001). The type of reconstruction (P < 0.001), operative time (P = 0.016), and postoperative complications (P = 0.001) were significantly associated with DGE by univariate analysis. Only the type of reconstruction (P < 0.001) was identified as an independent factor, which was associated with DGE by multivariate analysis. An antecolic Roux-en Y type duodenojejunostomy could be a useful reconstruction method after PPPD to prevent the occurrence of DGE.

Adjuvant gemcitabine plus S-1 chemotherapy after surgical resection for pancreatic adenocarcinoma

BACKGROUND The aim of this study was to determine the effectiveness of adjuvant gemcitabine plus S-1 chemotherapy for patients with pancreatic carcinoma. METHODS Patients admitted for curative surgery for pancreatic adenocarcinoma received adjuvant chemotherapy with 10 cycles of gemcitabine plus S-1 every 2 weeks. Each chemotherapy cycle consisted of intravenous gemcitabine, 700 mg/m(2), on day 1 and orally administered S-1, 50 mg/m(2), for 7 consecutive days, after which there was a 1-week pause of chemotherapy. RESULTS Twenty-seven patients were entered into this study. According to the TNM system, 4 (15%), 2 (7%), 6 (22%), and 15 (56%) patients were diagnosed with stage IA, IB, IIA, and IIB disease, respectively. Overall and disease-free survival rates were 86% and 60% at 1 year, 66% and 45% at 2 years, and 33% and 45% at 3 years, respectively. Toxicity during chemotherapy was mild. CONCLUSIONS Adjuvant gemcitabine plus S-1 chemotherapy appears to be a promising treatment for patients after surgical resection of pancreatic adenocarcinoma.

Intraductal papillary-mucinous neoplasms and mucinous cystic neoplasms of the pancreas differentiated by ovarian-type stroma

BACKGROUND Intraductal papillary-mucinous neoplasms (IPMN) and mucinous cystic neoplasms (MCN) of the pancreas have similar clinicopathologic findings. This study was intended to clarify clinicopathologic characteristics in IPMNs and MCNs differentiated by ovarian-type stroma. METHODS Medical records for 77 patients with pancreatic cystic neoplasms with mucin secretion were reviewed. Patients were divided into IPMN (n = 70) or MCN (n = 7) according to the presence of ovarian-type stroma, and clinicopathologic parameters were compared between groups. RESULTS IPMNs consisted of 32 adenomas, 12 borderline neoplasms, 13 adenocarcinomas in situ, and 13 invasive adenocarcinomas; MCNs included 6 adenomas and 1 invasive adenocarcinoma. The mean age of IPMN patients (66 years) was significantly older than that of MCN patients (55 years). The male:female ratio in IPMN (53/17) was significantly greater (P < .001) than in MCN (0/7). The location of the pancreatic mass differed, with 76% 0f IPMNs occurring in the head, while 86% of MCNs occurred in the body or tail. Mass mean size was significantly smaller (28 mm vs 78 mm, P < .001), and mean diameter of the main pancreatic duct was larger (6.8 mm vs 3.1 mm, P < .001) in IPMN than in MCN. Patulous papilla was present in 44% (31/70) of IPMNs, but none was present in MCNs. Communication between the cyst and main pancreatic duct was more frequent in IPMNs (67/70) than in MCNs (1/7). Overall 5-year survival rates were 84% (IPMN) and 100% (MCN). CONCLUSIONS Clinicopathologic differences between IPMN and MCN are much clearer when differentiated by presence of ovarian-type stroma. Favorable prognosis for both neoplasms is offered by complete resection.

Invasive intraductal papillary-mucinous neoplasm of the pancreas: comparison with pancreatic ductal adenocarcinoma.

The aim of this study was to clarify the clinicopathological differences between patients with invasive intraductal papillary‐mucinous neoplasm (IPMN) of the pancreas and pancreatic ductal adenocarcinoma.

Pancreatic Head Resection With Segmental Duodenectomy for Intraductal Papillary Mucinous Tumors of the Pancreas

Various modifications of organ-preserving pancreatic resections have been performed for intraductal papillary mucinous tumor (IPMT) of the pancreas. The aim of this study was to evaluate usefulness of pancreatic head resection with duodenal segmentectomy (PHRSD), which is one of the organpreserving pancreatic resections for IPMT. Pancreatic head resection with duodenal segmentectomy was indicated for the branch duct type of IPMT. Eight patients underwent PHRSD. The mean operative time was 390 minutes, and the mean blood loss was 1270 ml. Duodenal ischemia was prevented by preserving the duodenal branches of the gastroduodenal artery and the anterior inferior pancreaticoduodenal artery. Complications occurred in four patients: one with pancreatic leak, one with choledochoduodenal anastomotic stenosis, and two with delayed gastric emptying. However, no deaths occurred. The final pathologic diagnosis was adenoma in seven patients and carcinoma in situ in one patient. Six of eight patients had an adenoma with papillary growth in the main pancreatic duct. Postoperative pancreatic endocrine and exocrine functions were satisfactory. All patients were alive without recurrent disease at a median follow-up of 30 months. Pancreatic head resection with duodenal segmentectomy appears to be a useful procedure as an organ-preserving pancreatic resection for the branch duct type of IPMT, because this procedure allows a safe and complete resection of the pancreatic head without ischemia of the common bile duct and the duodenum.

Telomere Shortening and Telomerase Expression during Multistage Carcinogenesis of Intraductal Papillary Mucinous Neoplasms of the Pancreas

Intraductal papillary mucinous neoplasm (IPMN) of the pancreas has been increasingly identified as a precursor to infiltrating ductal adenocarcinoma. Telomerase activation in response to telomere crisis followed by telomere shortening is thought to be a crucial event in the development of most human cancers. The aim of this study was to determine when this event occurs in the context of histologically defined IPMN progression. We analyzed telomerase expression in 68 IPMN samples and assessed telomere length by quantitative fluorescence in situ hybridization in samples taken from 17 sequential IPMN patients that included 37 individual loci. Samples from pancreatic ductal adenocarcinomas (PDACs, n = 15) and chronic pancreatitis patients (n = 10) were also examined. Telomeres were significantly shortened in 36 (97.3%) of 37 IPMN loci, with average telomere length decreasing with IPMN progression. Notably, even adenoma IPMNs demonstrated a 50% reduction of telomere length in 7 of 14 foci examined. Marked telomere shortening was observed from the in situ IPMN carcinoma stage (P < 0.001; vs borderline IPMNs) through the invasive stage, although telomerase had been activated, indicating that telomeres had shortened to a critical length by this histological grade. Up-regulated human telomerase reverse transcriptase expression was detectable and increased gradually with cancer development and was primarily observed at the borderline IPMN stage and then in more advanced histopathologies. Progressive telomere shortening predominantly occurs during early IPMNs carcinogenesis before telomerase activation and progression from borderline to carcinoma in situ IPMNs is the critical stage of IPMNs carcinogenesis at which telomere dysfunction occurs.

Usefulness of a 13C-labeled mixed triglyceride breath test for assessing pancreatic exocrine function after pancreatic surgery

BACKGROUND Although the fecal elastase-1 test is a satisfactory pancreatic exocrine function test, breath tests that use stable isotopes have been developed recently as alternatives. We evaluated the usefulness of a (13)C-labeled mixed triglyceride breath test for assessing pancreatic exocrine function after pancreatic surgery. METHODS The breath test and the fecal elastase-1 test were performed on 7 healthy volunteers, 10 patients with chronic pancreatitis, and 95 patients after pancreatic surgery. The breath test was analyzed with isotope ratio mass spectrometry and the cumulative recovery of (13)CO(2) at 7 hours (% dose (13)C cum 7h) was calculated. The fecal elastase-1 concentration was determined immunoenzymatically. RESULTS Both the fecal elastase-1 concentration and the % dose (13)C cum 7h of chronic pancreatitis patients and pancreatic resection patients were less than those of healthy volunteers. In all subjects, % dose (13)C cum 7h correlated with the fecal elastase-1 concentration (n = 112, R(2) = 0.14, P < .01). Accuracy rates for clinical symptoms, including clinical steatorrhea, for the fecal test and the breath test were 62 and 88%, respectively. CONCLUSION The (13)C-labeled mixed triglyceride breath test might be more useful than the fecal elastase-1 test for evaluating pancreatic exocrine function after pancreatic resection.