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Background: Postoperative infection after pancreatectomy in patients with pancreatic cancer often leads to poor prognosis. The aim of this study was to determine the prognostic effect of postoperative infection in patients with pancreatic cancer., Methods: A multicenter cohort study was performed using a common database of patients with pancreatic cancer who underwent curative pancreatic resections between April 2013 and March 2015 at 15 high-volume centers in Japan. The rate of postoperative infection was determined, and patient demographic characteristics, clinicopathologic factors, and prognostic factors for overall survival were analyzed., Results: Of the 462 eligible patients who underwent curative pancreatectomy, postoperative infection occurred in 141 patients (31%), including 114 surgical site infections (25%), 50 remote infections (11%), and 23 combined infections (5%). Risk factors for postoperative infection included high body mass index, nondiabetes, and longer operation time. In the survival analysis, patients with postoperative infection had significantly worse overall survival than patients without postoperative infection. The median survival times were 21.9 and 33.0 months (P = .023), respectively, for patients with and without postoperative infection. According to the multivariate analysis for overall survival, lack of adjuvant therapy (P = .002), but not postoperative infection (P = .829), predicted poor prognosis. The multivariate analysis revealed that postoperative infection (P < .001) was an independent risk factor for lack of adjuvant therapy., Conclusion: Postoperative infection in patients with pancreatic cancer may indirectly worsen the prognosis by preventing timely adjuvant therapy., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: To determine a recommended dose for a biweekly combination neoadjuvant chemotherapy including gemcitabine, nab-paclitaxel, and S-1 (GAS) for patients with locally advanced pancreatic ductal adenocarcinoma (LAPC)., Methods: Patients with borderline resectable or unresectable LAPC without distant metastasis were eligible for this study. The planned dosages of gemcitabine (mg/m 2 , day 1), nab-paclitaxel (mg/m 2 , day 1), and S-1 (mg/day, days 1-7) were 800/100/60-100 at level 1, and 1000/125/60-100 at level 2. The treatment cycle was repeated every 2 weeks, and patients were assessed for resectability and response to the treatment after 6 cycles. This study was registered with UMIN Clinical Trial Registry (UMIN000016630)., Results: We enrolled 16 patients with LAPC in this study. At dose level 1, one of 8 patients experienced dose-limiting toxicity (DLT). One of the next 8 patients also experienced DLT at dose level 2. Based on these results, level 2 was considered the recommended dose for this regimen. Pancreatectomy with curative intent could be performed in 13 of the 16 patients. R0 resection was performed in 12 of 13 patients., Conclusion: In conclusion, recommended doses for a biweekly GAS chemotherapy regimen were determined as nab-paclitaxel: 125 mg/m 2 , gemcitabine: 1000 mg/m 2 on day 1, S-1: <1.25 m 2 , 60 mg; 1.25-1.5 m 2 , 80 mg; >1.5 m 2 , 100 mg twice a day on days 1-7. GAS chemotherapy showed good preliminary efficacy with mild toxicity in this study, and warrants a further phase 2 trial to investigate the efficacy of the GAS regimen for LAPC.

Background: Although serum carbohydrate antigen 19-9 (CA19-9), s-pancreas antigen-1 (SPan-1), and duke pancreatic monoclonal antigen type 2 (DUPAN-II) are commonly utilized tumor markers in pancreatic ductal adenocarcinoma (PDAC), it is still unclear which is the most useful for predicting prognosis after surgical resection. Here, we aimed to compare the prognostic impact of pre- and post-operative serum CA19-9, SPan-1, and DUPAN-II levels in patients with resectable PDAC., Methods: Pre-operative CA19-9, SPan-1, and DUPAN-II levels were analyzed to compare their prognostic values for resectable PDAC in 198 patients whose pre-operative tumor markers were available. The relationships of clinicopathological factors, including pre- and postoperative CA19-9, SPan-1, and DUPAN-II levels, with overall survival (OS) were analyzed using univariate and multivariate analyses in 149 patients for whom both pre- and postoperative tumor markers were available., Results: Elevated pre-operative CA19-9 (≥37 U/mL), SPan-1 (≥30 U/mL), and DUPAN-II (≥150 U/mL) levels were found in 113 (60%), 96 (51%), and 82 (43%) patients, respectively. In multivariate analysis, absence of adjuvant chemotherapy (hazard ratio [HR], 4.17; p = 0.001), R1 resection (HR, 1.90; p = 0.03), higher histological grade (HR, 1.99; p = 0.02), advanced UICC T factor (HR, N/A; p = 0.04) and elevated postoperative CA19-9 (HR, 3.39; p = 0.009) were identified as independent predictors for worse OS., Conclusion: When the prognostic impacts of pre- and post-operative serum CA19-9, SPan-1, and DUPAN-II levels in patients with resectable PDAC were compared, elevated postoperative CA19-9 was the strongest predictive marker of poor survival in the pre- and post-operative period., (Copyright © 2016 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background and Objectives: The aim of this study is to investigate the prognostic value of intratumoral expression of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), and orotate phosphoribosyltransferase (OPRT) in patients treated with S-1-based chemotherapy after surgical resection for pancreatic adenocarcinoma., Methods: Intratumoral TS, DPD, and OPRT expression was investigated in 106 patients with resected pancreatic adenocarcinoma by immunohistochemistry. Associations between clinicopathological factors, including intratumoral TS, DPD, and OPRT expression, and survival were evaluated by univariate and multivariate analyses., Results: Of 106 patients, 72 had received S-1-based adjuvant chemotherapy (S-1(+) group), and 34 had not (S-1(-) group). High TS, DPD, and OPRT expression was observed in 64%, 37%, and 66% of patients, respectively. Among S-1(+) group patients, survival was significantly better for patients with low DPD expression than for patients with high DPD expression (P = 0.022). Intratumoral DPD expression was the only independent prognostic factor for patients treated with S-1-based adjuvant chemotherapy by multivariate analysis (P = 0.037). Intratumoral TS and OPRT expression did not appear to influence survival., Conclusions: Intratumoral DPD expression may be a relevant predictive marker of survival benefit associated with S-1-based adjuvant chemotherapy for pancreatic adenocarcinoma., (Copyright © 2011 Wiley-Liss, Inc.)

Background: Pancreatic cancer is one of the most deadly cancers, and serum carbohydrate antigen 19-9 (CA19-9) level has been reported to be a useful prognostic marker in pancreatic cancer. The purpose of this study was to determine which prognostic factor (preoperative or postoperative serum CA19-9 level) is more useful., Methods: Pre- and postoperative serum CA19-9 levels were measured in 109 patients who underwent surgical resection for pancreatic cancer between 1998 and 2009, and their relationships to clinicopathological factors and overall survival were analyzed with univariate and multivariate methods., Results: In univariate analysis, tumor location (P = 0.019), postoperative adjuvant chemotherapy (P < 0.001), residual tumor factor status (P < 0.001), UICC pT stage (P = 0.004), lymph node metastasis (P = 0.015), and UICC final stage (P = 0.015) were significantly associated with overall survival. Differences in overall survival were significant between groups divided on the basis of four postoperative CA19-9 cutoff values (37, 100, 200, and 500 U/ml) but not significant between groups divided on the basis of the same four preoperative CA19-9 cutoff values. Pre- to postoperative increase in CA19-9 level also was significantly associated with poor prognosis. In multivariate analysis, postoperative adjuvant chemotherapy (hazard ratio, 1.59; P = 0.004) and postoperative CA19-9 cutoff value of 37 U/ml (HR, 1.64; P = 0.004) remained independent predictors of prognosis., Conclusions: Postoperative CA19-9 level is a better prognostic factor than preoperative CA19-9 level, and curative surgery for resectable pancreatic cancer should be tried regardless of the preoperative CA19-9 level.

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., (Copyright 2010 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: Middle pancreatectomy is infrequently performed in selected patients. The rationale is to preserve pancreatic function. This study evaluates a technique, operative outcomes, and long-term exocrine and endocrine pancreatic function of the middle pancreatectomy procedure., Methods: Nineteen patients who underwent middle pancreatectomy between 1996 and 2008 were reviewed. Indications included eight intraductal papillary-mucinous neoplasms, five endocrine tumors, one serous and two mucinous cystadenomas, and three other benign lesions. Reconstruction of the distal pancreatic remnant was performed with pancreaticogastrostomy using the duct-to-mucosa method in 16 patients and with Roux-en-Y end-to-end pancreaticojejunostomy in 3 patients., Results: Median operative time was 215 min. Perioperative mortality was nil. Morbidity was 53%, including 9 (47%) pancreatic fistulas. One patient with hemorrhage, complicated by a pancreatic fistula was successfully treated by endovascular embolization. No patients required postsurgical reoperation. Only one patient had clinical exocrine insufficiency requiring pancreatic enzyme supplementation. None developed postresection new-onset insulin-dependent diabetes., Conclusions: Middle pancreatectomy with pancreaticogastrostomy is feasible and reasonable technique. Although the incidence of pancreatic fistula formation may still be higher compared to conventional resection, long-term exocrine, and endocrine pancreatic function may be preserved. Thus, careful patient selection and experienced pancreatic surgeons in high-volume centers are of great importance.

Introduction: The aim of this study was to determine risk factors for exocrine pancreatic insufficiency after pancreatoduodenectomy (PD) with pancreaticogastrostomy (PG)., Material and Methods: A (13)C-labeled mixed triglyceride breath test was performed in 61 patients after PD to assess exocrine pancreatic function. Percent (13)CO(2) cumulative dose at 7 h <5% was considered diagnostic of exocrine pancreatic insufficiency. Abdominal computed tomography scans were utilized to assess the dilatation of the main pancreatic duct (MPD dilatation) in the remnant., Results: Thirty-eight of 61 patients (62.3%) were diagnosed with exocrine pancreatic insufficiency. Univariate analysis identified significant associations between two preoperative factors (preoperative impaired endocrine function and a hard pancreatic texture induced by preexisting obstructive pancreatitis), plus one postoperative factor (MPD dilatation caused by PG stricture) and exocrine pancreatic insufficiency (P < 0.05). Multivariate analysis determined that all three of these factors were independent factors (P < 0.05)., Conclusions: Although exocrine pancreatic insufficiency after PD may be partly explainable by preexisting obstructive pancreatitis prior to surgery, surgeons desiring to obtain better postoperative exocrine pancreatic function after PD would be well-advised to devote considerable attention to preventing PG stricture.

Objectives: Human telomerase reverse transcriptase (hTERT), one of the subunits of telomerase, is a promising diagnostic marker for pancreatic cancer. In the present study, we did a large-scale analysis of 115 preoperative pancreatic juice specimens to evaluate the feasibility of detection of hTERT expression by immunohistochemistry for preoperative diagnosis of pancreatic malignancy., Methods: The expression of hTERT was examined by immunohistochemistry in preoperative pancreatic juice samples., Results: In pancreatic juice samples, hTERT expression was detectable in 84% of pancreatic ductal adenocarcinomas (PDACs), whereas 62% of PDACs were positive by cytology. In intraductal papillary mucinous neoplasms (IPMNs), hTERT expression was detectable in 88% of malignant IPMNs, whereas only 22% were positive by cytology. The sensitivity, specificity, and overall accuracy of hTERT expression for differentiation between carcinoma and other benign diseases were 85.1%, 82.1%, and 84.3%, respectively, whereas the same values for cytologic accuracy were 47.1%, 89.3%, and 57.4%, respectively. When the results of cytology and hTERT expression were combined, the sensitivity and overall accuracy increased to 92.0% and 87.8%, respectively., Conclusions: Our results suggested that the assessment of hTERT expression in preoperative pancreatic juice increased the sensitivity and accuracy of diagnosis of PDACs and malignant IPMNs without using special techniques.

A 65-year-old Japanese male was referred to our hospital for evaluation of a main pancreatic duct obstruction. Two months previously, he had suffered an attack of acute pancreatitis that was resolved with conservative treatment. Dynamic contrast-enhanced study by multidetector row computed tomography revealed a well-enhanced 5 x 5 mm mass in the head of the pancreas with dilatation of the main pancreatic duct in the body and tail. On endoscopic retrograde pancreatography, obstruction of the main pancreatic duct in the head of the pancreas was noted. Pancreatic juice cytology was nondiagnostic. Endoscopic ultrasonography demonstrated a well-defined hypoechoic mass, about 5 mm in size, with distal main pancreatic duct dilatation. The patient underwent elective pylorus-preserving pancreaticoduodenectomy. Pathological examination revealed a well-differentiated endocrine tumor of the pancreas of uncertain behavior, 5 mm in size. Immunohistochemically, the tumor was diffusely positive for chromogranin A and synaptophysin, and focally it was positive for insulin, glucagon, and CA19-9; it was negative for gastrin. The final diagnosis was main pancreatic duct obstruction secondary to a nonfunctioning endocrine tumor of the pancreas of uncertain behavior. Of note, a small nonfunctioning endocrine tumor of the pancreas is important in the differential diagnosis of main pancreatic duct obstruction demonstrated by radiographic examinations.

Background: Few patients with pancreatic body or tail carcinoma are candidates for surgical resection, and the efficacy of postoperative adjuvant chemotherapy for patients with pancreatic body or tail carcinoma has not been elucidated. The aim of this study was to determine the effect of adjuvant gemcitabine and S-1 therapy for patients with adenocarcinoma of the body or tail of the pancreas who had undergone surgical resection by distal pancreatectomy., Materials and Methods: Medical records of 34 patients with pancreatic body or tail carcinoma who underwent surgical resection were reviewed retrospectively. Eighteen patients received postoperative adjuvant gemcitabine and S-1 chemotherapy. Univariate and multivariate models were used to analyze the effect of various clinicopathological factors on long-term survival., Results: There were no deaths due to surgery. Overall, 1-, 2-, and 5-year survival rates were 69%, 40%, and 25%, respectively (median survival time, 14.4 months). Univariate analysis revealed that adjuvant gemcitabine plus S-1 chemotherapy, blood transfusion, splenic artery invasion, lymph node metastasis, surgical margin status, and International Union Against Cancer stage were associated significantly with long-term survival (P < 0.05). Furthermore, use of a Cox proportional hazards regression model indicated that adjuvant gemcitabine plus S-1 chemotherapy and absence of lymph node metastasis were significant independent predictors of a favorable prognosis (P < 0.05)., Conclusion: Postoperative adjuvant gemcitabine plus S-1 chemotherapy may improve survival after surgical resection for pancreatic body or tail carcinoma.

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.

Background and Objectives: The aim of this study was to evaluate long-term pancreatic endocrine function following pancreatoduodenectomy with pancreaticogastrostomy., Methods: Records of 52 patients who had survived for three or more years following pancreatoduodenectomy with pancreaticogastrostomy were studied retrospectively. Serum HbA(1c) levels had been measured prior to and at 3- to 6-month intervals after surgery., Results: Three of 42 patients with normal preoperative serum HbA(1c) levels (5.8%) showed deterioration of glucose tolerance. Five of these eight patients developed a pancreatic fistula postoperatively. However, the average serum HbA(1c) levels of patients with normal preoperative serum HbA(1c) levels have remained within the normal range for 3-10 years after surgery., Conclusions: Pancreatic endocrine function was maintained for a long-term period after pancreatoduodenectomy with pancreaticogastrostomy. Impaired glucose tolerance appeared to be associated with postoperative pancreatic fistula formation., ((c) 2008 Wiley-Liss, Inc.)

We report a case of mixed ductal-endocrine carcinoma derived from intraductal papillary mucinous neoplasm (IPMN) of the pancreas. The tumor presented intermingled exocrine and endocrine carcinomatous components and expressed intense human telomerase reverse transcriptase (hTERT), further confirming the malignant features. This pathologically unique tumor is the first case of mixed ductal-endocrine carcinoma derived from pancreatic IPMN and telomerase activation could play a potential role in the neoplastic progression of mixed ductal-endocrine carcinomas of the pancreas., ((Copyright) 2008 Wiley-Liss, Inc.)

Pancreatic carcinoma is one of the most aggressive types of gastrointestinal malignancy, and its prognosis remains extremely dismal. The aim of this study was to identify useful prognostic factors for patients undergoing surgical resection for pancreatic carcinoma. Medical records of 89 patients with pancreatic carcinoma who underwent surgical resection were retrospectively reviewed. Univariate and multivariate models were used to analyze the effect of various clinicopathological factors on long-term survival. There were no operative deaths. Overall 1-, 2-, and 5-year survival rates were 59, 28, and 7%, respectively (median survival time, 12.1 months). Univariate analysis revealed that postoperative adjuvant chemotherapy, portal vein invasion, lymph node metastasis, extrapancreatic nerve plexus invasion, surgical margin status, UICC pT factor, and UICC stage were significantly associated with long-term survival (P<0.01). Furthermore, use of postoperative adjuvant chemotherapy and absence of extrapancreatic nerve plexus invasion were found to be significant independent predictors of a favorable prognosis using a Cox proportional hazard regression model (P<0.05). These results suggest that postoperative adjuvant chemotherapy may improve survival after surgical resection for pancreatic carcinoma and that extrapancreatic nerve plexus invasion indicates a poor prognosis for long-term survival.

Background: Human telomerase reverse transcriptase (hTERT), a catalytic subunit of telomerase, is a promising diagnostic candidate for pancreatic cancer. To evaluate the feasibility of immunohistochemistry (IHC) for the diagnosis of pancreatic cancer, hTERT expression and telomerase activity were assayed in pancreatic tissues, ex vivo brushing, and pancreatic juice samples with various pancreatic diseases., Methods: Telomerase activity was analyzed using the TRAP assay and hTERT was examined by IHC in 85 pancreatic tumor samples, 17 ex vivo pancreatic duct brushings, and 27 pancreatic juice samples., Results: In tissue samples, telomerase activity was positive in 83% of invasive ductal adenocarcinomas (IDCs) when the specificity was set at 100%, while hTERT was highly expressed in 88% of IDCs. In intraductal papillary mucinous neoplasms (IPMNs), the levels of telomerase activity increased gradually during progression, while hTERT expression was detectable in 8 of 8 malignant IPMNs and 1 of 2 borderline IPMNs. In pancreatic juice samples, 10 of 11 IDCs and 3 of 4 malignant IPMNs expressed hTERT, in which seven samples were not diagnosed as malignant on cytologic exam. The diagnoses of pancreatic cancer based on hTERT IHC exhibited high rates of sensitivity (87%), specificity (92%), and overall accuracy (89%), whereas the sensitivity of cytologic examination was 53%. The additional assessment of hTERT expression and telomerase activity could improve the sensitivity up to 100%., Conclusions: Our results suggested that hTERT expression in epithelia indicates malignant transformation in pancreatic tumors and immunohistochemical detection of hTERT in cells derived from pancreatic juice provides a potent method for cancer diagnosis.

The aim of this prospective study was to clarify differences in postoperative changes of serum or drainage fluid pancreatic amylase levels and serum C-reactive protein (CRP) levels between patients with a soft pancreatic texture and those with a hard pancreatic texture undergoing pancreatoduodenectomy (PD) with pancreaticogastrostomy. A total of 61 consecutive patients with resectable periampullary tumors undergoing PD were recruited. This population was divided into 27 patients with a hard pancreatic texture and 34 patients with a soft pancreatic texture. Drainage fluid total amylase or pancreatic amylase levels, serum total amylase or pancreatic amylase levels, and serum CRP levels were measured postoperatively. Clinicopathological data were also compared between two groups. Postoperative complications more frequently occurred in patients with a soft pancreatic texture compared with those with a hard pancreatic texture (P=0.029). Serum or drainage fluid pancreatic amylase levels and serum CRP levels of patients with a soft pancreatic texture were significantly higher than those of patients with a hard pancreatic texture after PD on postoperative days 1 and 2 (P<0.05). A soft pancreatic texture was identified as an only independent predictive factor of increased drainage fluid pancreatic amylase levels (P=0.006) and serum CRP levels (P=0.047). A soft pancreatic texture is closely associated with increased drainage fluid pancreatic amylase and serum CRP levels after PD. More careful post-PD management is needed for patients with a soft pancreatic texture.

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.

Background: Preoperative biliary drainage (PBD) is associated with bacterial contamination of bile, but the effects of PBD on morbidity after pancreatoduodenectomy remain controversial. The aim of this study was to characterize bile contamination to develop successful specific antibiotic prophylactic strategies for pancreatoduodenectomy., Methods: Ninety-one consecutive patients who underwent pancreatoduodenectomy for periampullary tumor were prospectively evaluated. Prophylactic antibiotics were selected based on preoperative bile cultures. Bile cultures and postoperative complications were compared in 46 patients who underwent PBD (drainage group) versus 45 patients who did not (nondrainage group)., Results: The incidence of positive bile cultures was higher in the drainage group (78%) than in the nondrainage group (36%) (P < 0.001). In the drainage group, positive bile cultures were frequently polymicrobial (61%) and demonstrated resistance to several antibiotics, including cefazolin (83%), cefmetazole (72%), and cefpirome (64%). Overall morbidity (30% and 22%) and infectious morbidity (13% and 11%) did not differ significantly between the drainage and nondrainage groups, respectively., Conclusions: PBD had a notable influence on bile microbial contamination, including a higher rate of antibiotic resistance. Therefore, specific antibiotic prophylaxis based on bile culture is required for preventing infectious complications in pancreatoduodenectomy patients who undergo PBD.

K-ras point mutation, p53 over-expression, and telomerase activity have been proposed as molecular markers for clinical diagnosis of pancreatic carcinoma. To evaluate the clinical usefulness of these markers, we performed comparative analysis in 61 resected pancreatic samples including 15 intraductal papillary-mucinous tumours (IPMTs), 4 mucinous cystic tumours, 37 ductal adenocarcinomas, and five chronic pancreatitis samples. K-ras point mutation, telomerase activity, and p53 overexpression were analyzed using mutant allele specific amplification, the telomeric repeat amplification protocol, and immunohistochemical staining, respectively. In malignant tumours, K-ras mutation, telomerase activity, and p53 overexpression were detectable in 76, 91, and 46%, respectively, while in benign tumours, these alterations were detectable in 38, 0, and 0%, respectively. Among 15 IPMTs, K-ras mutation was detectable in 4 (80%) of 5 IPMT-adenomas, 4 (80%) of 5 IPMT-carcinomas and 2 (66%) of 3 papillary-mucinous carcinomas, which are invasive carcinomas derived from IPMTs. Telomerase activity was not detectable in IPMT-adenomas, but was detected in all 5 IPMT-carcinomas and 3 papillary-mucinous carcinomas. p53 overexpression was not detected in IPMTs, but was detected in 2 (66%) of 3 papillary-mucinous carcinomas, indicating that telomerase is likely to be activated concomitant with carcinogenesis. These results suggest that telomerase activity is the most useful as a differential diagnostic marker between malignant and benign pancreatic tumours.