Identification of Cystic Lesions by Secondary Screening of Familial Pancreatic Cancer (FPC) Kindreds Is Not Associated with the Stratified Risk of Cancer.

OBJECTIVES: Intraductal papillary mucinous neoplasms (IPMNs) are associated with risk of pancreatic ductal adenocarcinoma (PDAC). It is unclear if an IPMN in individuals at high risk of PDAC should be considered as a positive screening result or as an incidental finding. Stratified familial pancreatic cancer (FPC) populations were used to determine if IPMN risk is linked to familial risk of PDAC. METHODS: This is a cohort study of 321 individuals from 258 kindreds suspected of being FPC and undergoing secondary screening for PDAC through the European Registry of Hereditary Pancreatitis and Familial Pancreatic Cancer (EUROPAC). Computerised tomography, endoscopic ultrasound of the pancreas and magnetic resonance imaging were used. The risk of being a carrier of a dominant mutation predisposing to pancreatic cancer was stratified into three even categories (low, medium and high) based on: Mendelian probability, the number of PDAC cases and the number of people at risk in a kindred. RESULTS: There was a median (interquartile range (IQR)) follow-up of 2 (0-5) years and a median (IQR) number of investigations per participant of 4 (2-6). One PDAC, two low-grade neuroendocrine tumours and 41 cystic lesions were identified, including 23 IPMN (22 branch-duct (BD)). The PDAC case occurred in the top 10% of risk, and the BD-IPMN cases were evenly distributed amongst risk categories: low (6/107), medium (10/107) and high (6/107) (P = 0.63). CONCLUSIONS: The risk of finding BD-IPMN was independent of genetic predisposition and so they should be managed according to guidelines for incidental finding of IPMN.

Differentiation of Autoimmune Pancreatitis from Pancreatic Cancer Remains Challenging.

BACKGROUND: Autoimmune pancreatitis (AIP) is an uncommon form of chronic pancreatitis. Whilst being corticosteroid responsive, AIP often masquerades radiologically as pancreatic neoplasia. Our aim is to appraise demographic, radiological and histological features in our cohort in order to differentiate AIP from pancreatic malignancy. METHODS: Clinical, biochemical, histological and radiological details of all AIP patients 1997-2016 were analysed. The initial imaging was re-reviewed according to international guidelines by three blinded independent radiologists to evaluate features associated with autoimmune pancreatitis and pancreatic cancer. RESULTS: There were a total of 45 patients: 25 in type 1 (55.5%), 14 type 2 (31.1%) and 6 AIP otherwise not specified (13.3%). The median (IQR) age was 57 (51-70) years. Thirty patients (66.6%) were male. Twenty-six patients (57.8%) had resection for suspected malignancy and one for symptomatic chronic pancreatitis. Three had histologically proven malignancy with concurrent AIP. Two patients died from recurrent pancreatic cancer following resection. Multidisciplinary team review based on radiology and clinical history dictated management. Resected patients (vs. non-resected group) were older (64 vs. 53, p = 0.003) and more frequently had co-existing autoimmune pathologies (22.2 vs. 55.6%, p = 0.022). Resected patients also presented with less classical radiological features of AIP, which are halo sign (0/25 vs. 3/17, p = 0.029) and loss of pancreatic clefts (18/25 vs. 17/17, p = 0.017). There were no differences in demographic features other than age. CONCLUSION: Despite international guidelines for diagnosing AIP, differentiation from pancreatic cancer remains challenging. Resection remains an important treatment option in suspected cancer or where conservative treatment fails.

Tumour stage and resection margin status are independent survival factors following partial pancreatoduodenectomy for duodenal adenocarcinoma.

INTRODUCTION: There is limited published evidence on duodenal carcinoma due to its rarity. This study aimed to evaluate gastric outlet obstruction and obstructive jaundice along with pathological variables as survival factors in patients with duodenal adenocarcinoma following resection. METHODS: Survival factor analysis was undertaken in patients undergoing duodenal cancer surgery from 1997 to 2015 in a single centre. RESULTS: There were 57 patients of whom 18 had gastric outlet obstruction and 14 had obstructive jaundice. Fifty-three had a partial pancreatoduodenectomy and four had palliative bypass. Perioperative mortality and morbidity were 4% (2/53) and 47% (25/53) respectively in resected patients. With a median (95% confidence interval, CI) follow-up of 72 (57-86) months, median overall and recurrence-free survival was 38 months (95% CI 28-113) and 27 months (95% CI 18-83) respectively. The 1 and 3-year overall survival rates were 84% (95% CI 74-95) and 52% (95% CI 39-69) respectively. Median overall survival was 19 months in patients with gastric outlet obstruction vs 53 months in those without (p = 0.026) and 28 months in patients with obstructive jaundice vs 38 months in those without (p = 0.611). Univariate analysis revealed that tumour stage, resection margin status, pre-operative albumin status, gastric outlet obstruction and age were associated with poorer overall and recurrence-free survival but multivariate analysis confirmed only tumour stage and resection margin status to be significant. CONCLUSION: Whereas gastric outlet obstruction in duodenal cancer appeared to be an important survival factor following partial pancreatoduodenectomy, multivariate analysis showed that only tumour stage and resection margin status were the key independent survival factors. Further multicentre studies are required to elucidate further characteristics of duodenal carcinoma and develop neoadjuvant/adjuvant management strategies.

The Liverpool duodenum-and spleen-preserving near-total pancreatectomy can provide long-term pain relief in patients with end-stage chronic pancreatitis.

PURPOSE: Total pancreatectomy may improve symptoms in patients with severe end-stage chronic pancreatitis. This might be achieved whilst preserving both the duodenum- and spleen-(DPSPTP). Mature clinical outcomes of this approach are presented. METHODS: Single-centre prospective cohort study performed between September 1996 and May 2016. Demographic, clinical details, pain scores and employment status were prospectively recorded during clinic attendance. RESULTS: Fifty-one patients (33 men, 18 women) with a median (interquartile range) age of 40.8 (35.3-49.4) years, a median weight of 69.8 (61.0-81.5) Kg and a median body mass index of 23.8 (21.5-27.8), underwent intended duodenum-and spleen-preserving near-total pancreatectomy for end-stage chronic pancreatitis. Aetiology was excess alcohol in 25, idiopathic (no mutation) in 15, idiopathic (SPINK-1/CFTR mutations) in two, hereditary (PRSS1 mutation) in seven and one each post-necrotising pancreatitis and obstructive pancreatic duct divisum in 1. The main indication for surgery was severe pain. Findings included parenchymal calcification in 79% and ductal calculi in 24%, a dilated main pancreatic duct in 57% and a dilated main bile duct in 17%, major vascular involvement in 27% and pancreato-peritoneal fistula in 2%. Postoperative complications occurred in 20 patients with two deaths. Median pain scores were 8 (7-8) preoperatively and 3 (0.25-5.75) at 5 years (p = 0.013). Opiate analgesic use was significantly reduced postoperatively (p = 0.048). Following surgery, 22 (63%) of 38 patients of working age re-entered employment compared with 12 (33%) working preoperatively (p = 0.016). CONCLUSION: Duodenum-and spleen-preserving near-total pancreatectomy provided long-term relief in adult patients with intractable chronic pancreatitis pain, with improved employment prospects.

Expression of dihydropyrimidine dehydrogenase (DPD) and hENT1 predicts survival in pancreatic cancer.

BACKGROUND: Dihydropyrimidine dehydrogenase (DPD) tumour expression may provide added value to human equilibrative nucleoside transporter-1 (hENT1) tumour expression in predicting survival following pyrimidine-based adjuvant chemotherapy. METHODS: DPD and hENT1 immunohistochemistry and scoring was completed on tumour cores from 238 patients with pancreatic cancer in the ESPAC-3(v2) trial, randomised to either postoperative gemcitabine or 5-fluorouracil/folinic acid (5FU/FA). RESULTS: DPD tumour expression was associated with reduced overall survival (hazard ratio, HR = 1.73 [95% confidence interval, CI = 1.21-2.49], p = 0.003). This was significant in the 5FU/FA arm (HR = 2.07 [95% CI = 1.22-3.53], p = 0.007), but not in the gemcitabine arm (HR = 1.47 [0.91-3.37], p = 0.119). High hENT1 tumour expression was associated with increased survival in gemcitabine treated (HR = 0.56 [0.38-0.82], p = 0.003) but not in 5FU/FA treated patients (HR = 1.19 [0.80-1.78], p = 0.390). In patients with low hENT1 tumour expression, high DPD tumour expression was associated with a worse median [95% CI] survival in the 5FU/FA arm (9.7 [5.3-30.4] vs 29.2 [19.5-41.9] months, p = 0.002) but not in the gemcitabine arm (14.0 [9.1-15.7] vs. 18.0 [7.6-15.3] months, p = 1.000). The interaction of treatment arm and DPD expression was not significant (p = 0.303), but the interaction of treatment arm and hENT1 expression was (p = 0.009). CONCLUSION: DPD tumour expression was a negative prognostic biomarker. Together with tumour expression of hENT1, DPD tumour expression defined patient subgroups that might benefit from either postoperative 5FU/FA or gemcitabine.

Intratumoural expression of deoxycytidylate deaminase or ribonuceotide reductase subunit M1 expression are not related to survival in patients with resected pancreatic cancer given adjuvant chemotherapy.

BACKGROUND: Deoxycytidylate deaminase (DCTD) and ribonucleotide reductase subunit M1 (RRM1) are potential prognostic and predictive biomarkers for pyrimidine-based chemotherapy in pancreatic adenocarcinoma. METHODS: Immunohistochemical staining of DCTD and RRM1 was performed on tissue microarrays representing tumour samples from 303 patients in European Study Group for Pancreatic Cancer (ESPAC)-randomised adjuvant trials following pancreatic resection, 272 of whom had received gemcitabine or 5-fluorouracil with folinic acid in ESPAC-3(v2), and 31 patients from the combined ESPAC-3(v1) and ESPAC-1 post-operative pure observational groups. RESULTS: Neither log-rank testing on dichotomised strata or Cox proportional hazard regression showed any relationship of DCTD or RRM1 expression levels to survival overall or by treatment group. CONCLUSIONS: Expression of either DCTD or RRM1 was not prognostic or predictive in patients with pancreatic adenocarcinoma who had had post-operative chemotherapy with either gemcitabine or 5-fluorouracil with folinic acid.

Immunohistochemical hENT1 expression as a prognostic biomarker in patients with resected pancreatic ductal adenocarcinoma undergoing adjuvant gemcitabine-based chemotherapy.

BACKGROUND: Human equilibrative nucleoside transporters (hENTs) are transmembranous proteins that facilitate the uptake of nucleosides and nucleoside analogues, such as gemcitabine, into the cell. The abundance of hENT1 transporters in resected pancreatic ductal adenocarcinoma (PDAC) might make hENT1 a potential biomarker of response to adjuvant chemotherapy. The aim of this study was to see whether hENT1 expression, as determined by immunohistochemistry, was a suitable predictive marker for subsequent treatment with gemcitabine-based adjuvant chemotherapy. METHODS: A systematic review was performed, searching databases from January 1997 to January 2016. Articles pertaining to hENT1 immunohistochemical analysis in resected PDAC specimens from patients who subsequently underwent adjuvant gemcitabine-based chemotherapy were identified. Eligible studies were required to contain survival data, reporting specifically overall survival (OS) and disease-free survival (DFS) with associated hazard ratios (HRs) stratified by hENT1 status. RESULTS: Of 42 articles reviewed, eight were suitable for review, with seven selected for quantitative meta-analysis. The total number of patients included in the meta-analysis was 770 (405 hENT1-negative, 365 hENT1-positive). Immunohistochemically detected hENT1 expression was significantly associated with both prolonged DFS (HR 0·58, 95 per cent c.i. 0·42 to 0·79) and OS (HR 0·52, 0·38 to 0·72) in patients receiving adjuvant gemcitabine but not those having fluoropyrimidine-based adjuvant therapy. CONCLUSION: Expression of hENT1 is a suitable prognostic biomarker in patients undergoing adjuvant gemcitabine-based chemotherapy.

The Liverpool uveal melanoma liver metastases pathway: outcome following liver resection.

AIM: To determine the outcome of patients that underwent liver resection for metastases from uveal melanoma. METHODS: Over a 9-year period, patients referred with uveal melanoma metastases were included. Following treatment of primary uveal melanoma, high-risk patients were offered to be enrolled into a 6-monthly non-contrast liver magnetic resonance imaging (MRI) surveillance. Following detection of liver metastases, patients were staged with a contrast-enhanced (Primovist(®)) liver MRI, computer tomography (CT) of the thorax and staging laparoscopy. RESULTS: 155 patients were referred with uveal melanoma liver metastases, of which 17 (11.0%) patients had liver resection and one patient was treated with percutaneous radio-frequency ablation. The majority of patients undergoing liver resection were treated with multiple metastectomies (n = 8) and three patients had major liver resections. The overall median survival for patients treated with surgery/ablation was 27 (14-90) months, and this was significantly better compared to patients treated palliatively [median = 8(1-30) months, P < 0.001]. Following surgery, 11 patients had recurrent disease [median = 13(6-36) months]. Patients who had undergone a major liver resection had a significantly poorer disease-free survival (P = 0.037). CONCLUSIONS: Patients who can undergo surgical resection for metastatic uveal melanoma have a more favorable survival compared to those who do not.

Systematic review and meta-analysis of follow-up after hepatectomy for colorectal liver metastases.

BACKGROUND: The evidence surrounding optimal follow-up after liver resection for colorectal metastases remains unclear. A significant proportion of recurrences occur in the early postoperative period, and some groups advocate more intensive review at this time. METHODS: A systematic review of literature published between January 2003 and May 2010 was performed. Studies that described potentially curative primary resection of colorectal liver metastases that involved a defined follow-up protocol and long-term survival data were included. For meta-analysis, studies were grouped into intensive (more frequent review in the first 5 years after resection) and uniform (same throughout) follow-up. RESULTS: Thirty-five studies were identified that met the inclusion criteria, involving 7330 patients. Only five specifically addressed follow-up. Patients undergoing intensive early follow-up had a median survival of 39·8 (95 per cent confidence interval 34·3 to 45·3) months with a 5-year overall survival rate of 41·9 (34·4 to 49·4) per cent. Patients undergoing routine follow-up had a median survival of 40·2 (33·4 to 47·0) months, with a 5-year overall survival rate of 38·4 (32·6 to 44·3) months. CONCLUSION: Evidence regarding follow-up after liver resection is poor. Meta-analysis failed to identify a survival advantage for intensive early follow-up.

Cholecystectomy-related bile duct and vasculobiliary injuries.

BACKGROUND: Combined vasculobiliary injury is a serious complication of cholecystectomy. This study examined medium- to long-term outcomes after such injury. METHODS: Patients referred to this institution with Strasberg type E bile duct injuries were identified from a prospectively maintained database (1990-2010). Long-term outcomes were evaluated by chart review. RESULTS: Sixty-three patients were referred with bile duct injury alone (45 patients) or vasculobiliary injury (18). Thirty patients (48 per cent) had septic complications before transfer. Twenty-six patients (41 per cent) had long-term biliary complications over a median follow-up of 96 (range 12-245) months. Nine patients (3 with bile duct injury, 6 with vasculobiliary injury) required further interventions after a median of 22 (8-38) months; five required biliary surgical revision and four percutaneous dilatation of biliary strictures. Vasculobiliary injury and injury-related sepsis were independent risk factors for treatment failure: hazard ratio 7·79 (95 per cent confidence interval 2·80 to 21·70; P < 0·001) and 4·82 (1·69 to 13·68; P = 0·003) respectively. CONCLUSION: Outcome following bile duct injury repair was worse in patients with concomitant vasculobiliary injury and/or sepsis.

Meta-analysis of immunohistochemical prognostic markers in resected pancreatic cancer.

BACKGROUND: The potential prognostic value of several commonly investigated immunohistochemical markers in resected pancreatic cancer is variably reported. The objective of this study was to conduct a systematic review of literature evaluating p53, p16, smad4, bcl-2, bax, vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) expression as prognostic factors in resected pancreatic adenocarcinoma and to conduct a subsequent meta-analysis to quantify the overall prognostic effect. METHODS: Relevant literature was identified using Medline, EMBASE and ISI Web of Science. The primary end point was overall survival assessed on univariate analysis. Only studies analysing resected pancreatic adenocarcinoma were eligible for inclusion and the summary log(e) hazard ratio (logHR) and variance were pooled using an inverse variance approach. Evidence of heterogeneity was evaluated using the χ(2) test for heterogeneity and its impact on the meta-analysis was assessed by the I(2) statisic. Hazard ratios greater than one reflect adverse survival associated with positive immunostaining. RESULTS: Vascular endothelial growth factor emerged as the most potentially informative prognostic marker (11 eligible studies, n=767, HR=1.51 (95% confidence interval, CI=1.18-1.92)) with no evidence of any significant publication bias (Egger's test, P=0.269). Bcl-2 (5 eligible studies, n=314, HR=0.51 (95% CI=0.38-0.68)), bax (5 studies, n=274, HR=0.63 (95% CI=0.48-0.83)) and p16 (3 studies, n=229, HR=0.63 (95% CI=0.43-0.92)) also returned significant overall survival differences, but in smaller patient series due to a lack of evaluable literature. Neither p53 (17 studies, n=925, HR=1.22 (95% CI=0.96-1.56)), smad4 (5 studies, n=540, HR=0.88 (95% CI=0.61-1.27)) nor EGFR (4 studies, n=250, HR=1.35 (95% CI=0.80-2.27)) was found to represent significant prognostic factors when analysing the pooled patient data. There was evidence of significant heterogeneity in four of the seven study groups. CONCLUSION: These results support the case for immunohistochemical expression of VEGF representing a significant and reproducible marker of adverse prognosis in resected pancreatic cancer.

Considerations for the use of plasma cytokeratin 18 as a biomarker in pancreatic cancer.

BACKGROUND: Enzyme-linked immunoassays of full-length (M65) and/or caspase-cleaved (M30) cytokeratin 18 (CK18) released from epithelial cells undergoing necrosis and/or apoptosis, respectively, may have prognostic or predictive biomarker utility in a range of solid tumour types. Characterisation of baseline levels of circulating full length and cleaved CK18 specifically in patients with pancreatic cancer. METHODS: Plasma samples from 103 patients with pancreatic cancer stored at -80 degrees C were assayed for M65 and M30 levels. The median (inter-quartile range (IQR)) duration of plasma storage was 34 (23-57) months. Patients with metastatic disease (n=19) were found to have greater median (IQR) M65 levels (1145 (739-1698) U l(-1)) compared with the locally advanced (n=20; 748 (406-1150) U l(-1)) and resected (n=64; 612 (331-987) U l(-1)) patients (P=0.002). Elevated M65 levels were associated with poorer overall survival on univariate (P<0.001) but not multivariate (P=0.202) analysis. M65 concentrations also exhibited significant associations with concurrent serum-bilirubin levels (P<0.001) and the duration of plasma storage (P<0.001). CONCLUSIONS: Baseline plasma CK18 levels in pancreatic cancer are affected by the presence of obstructive jaundice and prolonged plasma storage. Clinical biomarker studies utilising serial CK18 levels are warranted in pancreatic cancer, provided consideration is given to these potentially confounding factors.

Adjuvant 5-fluorouracil and folinic acid vs observation for pancreatic cancer: composite data from the ESPAC-1 and -3(v1) trials.

The ESPAC-1, ESPAC-1 plus, and early ESPAC-3(v1) results (458 randomized patients; 364 deaths) were used to estimate the effectiveness of adjuvant 5FU/FA vs resection alone for pancreatic cancer using meta-analysis. The pooled hazard ratio of 0.70 (95% CI=0.55-0.88) P=0.003, and the median survival of 23.2 (95% CI=20.1-26.5) months with 5FU/FA vs 16.8 (95% CI=14.3-19.2) months with resection alone supports the use of adjuvant 5FU/FA in pancreatic cancer.

Meta-analyses of chemotherapy for locally advanced and metastatic pancreatic cancer: results of secondary end points analyses.

In advanced pancreatic cancer, level one evidence has established a significant survival advantage with chemotherapy, compared to best supportive care. The treatment-associated toxicity needs to be evaluated. This study examines the secondary outcome measures for chemotherapy in advanced pancreatic cancer using meta-analyses. A systematic review was undertaken employing Cochrane methodology, with search of databases, conference proceedings and trial registers. The secondary end points were progression-free survival (PFS)/time to progression (TTP) (summarised using the hazard ratio (HR)), response rate and toxicity (summarised using relative risk). There was no significant advantage of 5FU combinations vs 5FU alone for TTP (HR=1.02; 95% CI=0.85-1.23) and toxicity. Progression-free survival (HR 0.78; CI 0.70-0.88), TTP (HR=0.85; 95% CI=0.72-0.99) and overall response rate (RR=0.56; 95% CI=0.46-0.68) were significantly better for gemcitabine combination chemotherapy, but offset by the greater grade 3/4 toxicity thrombocytopenia (RR=1.94; 95% CI=1.32-2.84), leucopenia (RR=1.46; 95% CI=1.15-1.86), neutropenia (RR=1.48; 95% CI=1.07-2.05), nausea (RR=1.77; 95% CI=1.37-2.29), vomiting (RR=1.64; 95% CI=1.24-2.16) and diarrhoea (RR=2.73; 95% CI=1.87-3.98). There is no significant advantage on secondary end point analyses for administering 5FU in combination over 5FU alone. There is improved PFS/TTP and response rate, with gemcitabine-based combinations, although this comes with greater toxicity.

Preoperative resolution of jaundice following biliary stenting predicts more favourable early survival in resected pancreatic ductal adenocarcinoma.

INTRODUCTION: Despite the widespread use of endoscopic biliary stenting in patients presenting with potentially resectable pancreatic cancer, there is no general consensus regarding whether this represents a superior management approach over expeditious surgical intervention. The objective of this study was to investigate the influence of preoperative biliary stenting and resolution of jaundice on subsequent postoperative survival following resection for pancreatic cancer. METHODS: 155 patients undergoing partial pancreatoduodenectomy for pancreatic ductal adenocarcinoma between January 1997 and August 2007 were identified from a prospectively maintained database. RESULTS: There was no survival difference when comparing patients undergoing preoperative biliary drainage (n = 130) with those who did not (n = 25) (log rank, P = 0.981). When analysing individual prognostic factors as continuous variables in univariate Cox analysis, lower albumin levels (P = 0.016), elevated alkaline phosphatase levels (P = 0.011) and elevated CRP levels (P = 0.021) were associated with poorer overall survival. Multivariable Cox regression demonstrated that both albumin (P = 0.008) and CRP (P = 0.038) remained significant independent predictors of overall survival alongside lymph node ratio (P = 0.018). Although preoperative bilirubin levels were not associated with overall survival when analysed as a continuous variable (Cox, P = 0.786), the presence of jaundice (i.e., bilirubin >35 micromol/l) at the time of surgery was a significant adverse predictor of early survival in patients undergoing preoperative biliary drainage (Breslow-Gehan-Wilcoxon, P = 0.013) and remained a significant predictor of early survival when included in a further Cox analysis with censoring of cases who survived beyond 6 months (Cox, P = 0.017). CONCLUSION: These results suggest that the presence of jaundice at the time of resection has an adverse impact on early, but not overall, postoperative survival in pancreatic cancer patients undergoing preoperative biliary drainage.

Carbohydrate antigen 19.9 accurately selects patients for laparoscopic assessment to determine resectability of pancreatic malignancy.

BACKGROUND: Laparoscopy with laparoscopic ultrasonography (L-LUS) may be useful in the selection of patients for surgery to resect peripancreatic malignancy in addition to contrast-enhanced computed tomography (CE-CT). The present prospective study assessed the strategy of using carbohydrate antigen 19.9 (CA19.9) levels to select patients for L-LUS. METHODS: Patients with suspected peripancreatic malignancy that appeared resectable on CE-CT were selected for immediate surgery if CA19.9 was low (up to 150 kU/l, or up to 300 kU/l if serum bilirubin was above 35 micromol/l), or to L-LUS if CA19.9 was high (over 150 kU/l, or over 300 kU/l if serum bilirubin was above 35 micromol/l). Data were assessed to determine the clinical utility of this strategy. RESULTS: A total of 94 patients went straight to surgery, of whom 65 proved resectable: 63 of 80 with a low CA19.9 level but only two of 14 with a high CA19.9 level and gastric outlet obstruction. From 55 patients with high CA19.9 levels, L-LUS correctly identified 26 of 31 resectable tumours and eight of 24 unresectable tumours. CONCLUSION: Using CA19.9 levels to help select patients with pancreatic malignancy for immediate surgery or L-LUS for further assessment of resectability effectively increased resection rates and reduced unnecessary laparotomies.

Complications and follow-up after pancreas-preserving total duodenectomy for duodenal polyps.

BACKGROUND: Patients with duodenal polyps are at risk of duodenal cancer. Pancreas-preserving total duodenectomy (PPTD) is an alternative to partial pancreatoduodenectomy. METHODS: Twelve patients (seven men and five women) with a median age of 59 (interquartile range (i.q.r.) 50-67) years underwent PPTD for large (over 20 mm) solitary polyps or multiple (more than three) duodenal polyps confined to the muscularis propria on endoscopic ultrasonography. RESULTS: Median hospital stay was 21 (i.q.r. 10-36) days with no deaths and no blood transfusion. Six patients developed postoperative complications, one requiring reoperation. Histology demonstrated gastrointestinal stromal tumour in three patients, low-grade dysplasia in one, moderate-grade dysplasia in eight and duodenal intramucosal adenocarcinoma in one. During a median follow-up of 20 (i.q.r. 8-41) months one patient experienced recurrent acute pancreatitis (due to hypertriglyceridaemia) and one developed a jejunal adenocarcinoma in the neoduodenum. CONCLUSION: The morbidity of PPTD is similar to that of partial pancreatoduodenectomy, but PPTD preserves the whole pancreas and reduces the number of anastomoses.

Preoperative CA19-9 levels and lymph node ratio are independent predictors of survival in patients with resected pancreatic ductal adenocarcinoma.

BACKGROUND: The aim of this study was to identify whether preoperative CA19-9 levels might represent an independent prognostic marker for overall survival in patients undergoing resection for pancreatic ductal adenocarcinoma, and to describe the relationship between CA19-9 and tumour histology. METHODS: 109 patients who had a pancreatoduodenectomy for pancreatic ductal adenocarcinoma with recorded preoperative CA19-9 levels were identified from a prospectively maintained database (1997-2006). Multivariate analysis was conducted using a Cox proportional hazards model with continuous covariates where possible. RESULTS: The median survival of 64 patients with a preoperative CA19-9 level >150 kU/l was 10.4 months while in 45 patients with a CA19-9 level 150 kU/l were associated with a larger, more poorly differentiated tumour along with an increased likelihood of a positive resection margin status (all p < 0.05). Preoperative CA19-9 levels (p = 0.030) and lymph node ratio (p = 0.042) emerged as independent predictors of survival on multivariate analysis. CONCLUSIONS: Preoperative CA19-9 levels and lymph node ratio were significant predictors of survival in resected pancreatic ductal adenocarcinoma.

Both HIV- and EIAV-based lentiviral vectors mediate gene delivery to pancreatic cancer cells and human pancreatic primary patient xenografts.

Few effective treatments for pancreatic cancer exist, especially for patients with advanced disease. Gene therapy alone, or combined with current treatments, offers an alternative approach. Here we examined the potential of primate and nonprimate lentivectors to mediate gene delivery to this cancer type. VSV-G pseudotyped lentivectors based on human immunodeficiency type-1 virus (HIV-1) and equine infectious anemia virus (EIAV), containing the enhanced green fluorescent protein (EGFP) reporter gene were prepared and characterized for titer and RNA content. Vector-mediated gene delivery was examined in five pancreatic cancer cell lines in vitro, and in MiaPaCa-2 cells as well as in five human primary patient biopsies xenografted subcutaneously in nude mice. While individual cell lines showed differential sensitivities to transduction with lentivectors, all cell lines were successfully transduced with both vector types. Similarly, both vectors transduced MiaPaCa-2 and all of the human primary patient xenografts. We observed 6-29% transduction with HIV-based vectors (n=3 xenografts) and 1.8-30% with EIAV-based vectors (n=4 xenografts). Long-term EIAV-mediated gene expression was recorded in cell lines for up to 6 months. We conclude that these vectors have potential as mediators of clinical gene therapy for pancreatic cancer treatment. Moreover, they are useful laboratory research tools for pancreatic cancer research.

Objective assessment of trainee operative experience in a tertiary hepatobiliary unit.

INTRODUCTION: Indicative numbers for completion of training (CCT) in the UK requires 35 upper Gastrointestinal/Hepatobiliary resections and 110 (50 non HPB trainees) cholecystectomies. We aim to identify whether the training experience in our centre meets the CCT requirements for hepatobiliary surgery and compare training opportunities to those in international fellowships. METHODS: We retrospectively reviewed our hospital's operating theatre database for all patients undergoing a liver or gallbladder resection between January 2008 and July 2015 using corresponding procedural codes and consultant name. The cohort was categorized based on case and primary operating surgeon. The training grade of the surgeon was split into junior registrar (ST3/5), senior registrar (ST6/8) and senior fellow (post-CCT). RESULTS: Over a 7.5 year period we performed 2301 hepatobiliary procedures. The senior fellows and senior registrars performed a median of 42 liver resections (range 15-94) and 77 (range 35-110) cholecystectomies as the primary operator in any given 12 month period. The academic output for the unit was 104 over this period, with a median publication rate of 1.34 papers/trainee in any given 12 months. 15/16 senior fellow/senior registrars went on to secure substantive hepatobiliary consultant posts. CONCLUSIONS: Our centre delivers in excess of the required operative volume and clinical competencies for CCT in Hepatobiliary surgery in a 12 month period and exposure of trainees to operative experience is commensurate to the best performing international fellowships.