Clinical and radiological features that predict malignant transformation in cystic lesions of the pancreas: a retrospective case note review.

Background: Pancreatic cystic lesions (PCL) are being detected with increasing frequency. Current methods of stratifying risk of malignant transformation are imperfect. This study aimed to determine the frequency of pancreatic malignancy in patients with PCL and define clinical and radiological features that predict malignant transformation in patients managed by surgery and/or surveillance. Methods: A retrospective cohort of adults who were evaluated in a tertiary hepatopancreaticobiliary centre between January 2000 - December 2013 with a confirmed PCL and followed up for at least 5 years. All cystic lesions were discussed at a weekly multidisciplinary meeting. Results: Of the 1,090 patients diagnosed with a PCL, 768 patients were included in the study: 141 patients were referred for immediate pancreatic resection, 570 entered surveillance while 57 had a malignant PCL which was unresectable at diagnosis (n=47) or were unfit for surgery (n=10). In those who were resected following presentation, malignancy was present in 38%. During follow-up 2% of those entering a surveillance programme underwent malignant transformation. Clinical and radiological features associated with a high-risk PCL included older age, symptoms, associated solid component or dilated main pancreatic duct. In intraductal papillary mucinous neoplasms, larger size was not a feature of malignant transformation (benign vs. malignant 30mm vs. 23mm; P= 0.012). Conclusion: The sensitivity of standard diagnostic tests leading to immediate surgery for high-risk PCL (malignant or mucinous) was 92% but with a specificity of just 5%. Surveillance of PCL without high-risk features within a multidisciplinary meeting was associated with a low incidence of cancer development, supporting the use of worrisome clinical and radiological features in the initial stratification of PCL.

Radiological tumor density and lymph node size correlate with survival in resectable adenocarcinoma of the pancreatic head: A retrospective cohort study.

INTRODUCTION: Tumors within the pancreatic head show a variable density and enhancement on computerized tomography (CT). The relationship between the radiological appearance of pancreatic adenocarcinoma on CT and survival remains unclear. The aim of this study was to evaluate the relationship between the tumor density on CT and survival. We also evaluated the correlation between lymph node (LN) size and overall survival in patients undergoing pancreaticoduodenectomy for head of pancreas adenocarcinoma. MATERIALS AND METHODS: Case records of patients undergoing pancreaticoduodenectomy for the adenocarcinoma of pancreas head, between 2005 and 2009, were evaluated. CT was interpreted to document tumor density - Hounsfield unit (HU) and LN size of enlarged LNs. Histology was analyzed to review tumor differentiation and LN status. Survival was correlated with LN size and tumor density (HU). RESULTS: Increasing tumor density was significantly associated with an adverse outcome (P = 0.042, hazard ratio [HR] 1.034, 1.002-1.067 95% confidence interval [95% CI]). Patients with well-differentiated tumors had significantly lower tumor density as compared to moderately differentiated tumors (39.00 ± 26.00 vs. 71.31 ± 21.03 HU, P = 0.005). LN size more than 1 cm irrespective of LN status strongly correlated with the survival and was found to be an important prognostic factor (19.37 ± 2.71 months vs. 27.44 ± 2.74 months; P = 0.025; HR 2.70; 1.09-6.68 95% CI). CONCLUSION: Increasing pancreatic tumor density and the lymph nodal size of more than 1 cm are strong predictors of unfavorable overall survival for resectable adenocarcinoma of the pancreatic head. Further studies are required to identify the value of these proposed prognostic factors.

Scoring System to Predict Pancreatic Fistula After Pancreaticoduodenectomy: A UK Multicenter Study.

OBJECTIVE: To validate a preoperative predictive score of postoperative pancreatic fistula (POPF). Other risk factors for POPF were sought in an attempt to improve the score. BACKGROUND: POPF is the major contributor to morbidity after pancreaticoduodenectomy (PD). A preoperative score [using body mass index (BMI) and pancreatic duct width] to predict POPF was tested upon a multicenter patient cohort to assess its performance. METHODS: Patients undergoing PD at 8 UK centers were identified. The association between the score and other pre-, intra-, and postoperative variables with POPF was assessed. RESULTS: A total of 630 patients underwent PD with 141 occurrences of POPF (22.4%). BMI, perirenal fat thickness, pancreatic duct width on computed tomography and at operation, bilirubin, pancreatojejunostomy technique, underlying pathology, T stage, N stage, R status, and gland firmness were all significantly associated with POPF. The score predicted POPF (P < 0.001) with a higher predictive score associated with increasing severity of POPF (P < 0.001). Stepwise multivariate analysis of pre-, intra-, and postoperative variables demonstrated that only the score was consistently associated with POPF. A table correlating the risk score to actual risk of POPF was created. CONCLUSIONS: The predictive score performed well and could not be improved. This provides opportunities for individualizing patient consent and selection, and treatment and research applications.

Redefining the R1 resection for pancreatic ductal adenocarcinoma: tumour lymph nodal burden and lymph node ratio are the only prognostic factors associated with survival.

INTRODUCTION: The presence of positive nodal disease (LND) and the number of lymph nodes involved (LNB) are known to be significant prognostic markers for resected adenocarcinoma of the pancreas. In addition, the ratio of the number of involved nodes to the number of nodes resected known as the lymph node ratio (LNR) is emerging as an important prognostic marker. The role of the resection margin (RM) as presently defined (R1 ≤ 1 mm) is unclear as results differ based on the dataset. The aim of this study was to assess the impact of nodal disease and a redefined RM on outcome. MATERIAL AND METHODS: Retrospective analysis of pancreatic head resections for adenocarcinomas from 2003-2009. The RM was re-analysed based on tumour clearance and categorized into: histopathological evidence of a tumour; ≤ 0.5 mm, ≤ 1 mm, ≤ 1.5 mm, or ≤ 2.0 mm of the actual surgical resection margin. The impact of histopathological variables on cancer-specific survival (CSS) and disease-free survival (DFS) was analysed. RESULTS: LND, LNB and LNR were independent prognostic markers for CSS (P = 0.048, 0.003, 0.016) but, did not influence DFS. A LNR < 0.143 was associated with a higher CSS [38.16 ± 4.69 versus 20.59 ± 2.20 months, P = 0.0042, hazard ratio (HR) 3.74 (95% confidence interval (CI) 1.52-9.23)]. An R1 RM was not associated with CSS or DFS on multivariate analysis, irrespective of the distance. LNB and LNR maintained independent significance irrespective of the size of the RM. CONCLUSION: LNB and LNR are the only prognostic factors for CSS in patients with pancreatic head adenocarcinoma, but do not predict recurrence. Microscopic RMs does not seem to influence the outcome even when redefined. Further prospective studies are indicated to substantiate these findings.

Maternal obesity programs offspring nonalcoholic fatty liver disease by innate immune dysfunction in mice.

UNLABELLED: The global prevalence of obesity-induced liver disease (nonalcoholic fatty liver disease; NAFLD) is rising. Suggested causes include a role for in utero influences of maternal obesity compounded by the availability of energy-dense foods throughout postnatal life. Using a physiologically relevant model, we investigated the role of the innate immune system in liver injury induced by maternal obesity followed by a postnatal obesogenic diet. Female C57BL/6J mice were fed a standard or obesogenic diet before and throughout pregnancy and during lactation. Female offspring were weaned onto a standard or obesogenic diet at 3 weeks postpartum. Biochemical and histological indicators of dysmetabolism, NAFLD and fibrosis, analysis of profibrotic pathways, liver innate immune cells, and reactive oxygen species (ROS) were investigated at 3, 6, and 12 months. Female offspring exposed to a postweaning obesogenic diet (OffCon-OD) demonstrated evidence of liver injury, which was exacerbated by previous exposure to maternal obesity (OffOb-OD), as demonstrated by raised alanine aminotransferase, hepatic triglycerides, and hepatic expression of interleukin (IL)-6, tumor necrosis factor alpha, transforming growth factor beta, alpha smooth muscle actin, and collagen (P < 0.01). Histological evidence of hepatosteatosis and a more-robust NAFLD phenotype with hepatic fibrosis was observed at 12 months in OffOb-OD. A role for the innate immune system was indicated by increased Kupffer cell numbers with impaired phagocytic function and raised ROS synthesis (P < 0.01), together with reduced natural killer T cells and raised interleukin (IL)-12 and IL-18. CONCLUSION: Maternal obesity in the context of a postnatal hypercalorific obesogenic diet aggressively programs offspring NAFLD associated with innate immune dysfunction, resulting in a comprehensive phenotype that accurately reflects the human disease.

Intracellular oxygenation and cytochrome oxidase C activity in ischemic preconditioning of steatotic rabbit liver.

BACKGROUND: Mild to moderate steatotic livers are used as marginal donors in liver transplantation. Very little is known about the mechanisms of ischemia reperfusion (IR) injury (IRI) in fatty liver. This study aimed to establish whether cytochrome oxidase C (COX) activity is compromised by IRI in fatty liver and whether ischemic preconditioning (IPC) can protect COX activity. METHODS: New Zealand rabbits were fed on a high-cholesterol diet for 8 weeks to induce moderate hepatic steatosis. Three groups were tested. The IR group underwent 60 minutes of ischemia, followed by 7 hours of reperfusion. The IPC group (IPC + IR) underwent 5 minutes of ischemia, followed by 10 minutes of reperfusion and then 60 minutes of ischemia and 7 hours of reperfusion. The control group (sham) underwent the same surgical procedure, but ischemia was not induced. Deoxyhemoglobin, oxyhemoglobin, and change in the redox state of COX was continuously monitored in vivo by near-infrared spectroscopy. COX and citrate synthase (CS) activity assays were carried out on liver biopsy specimens in vitro. Bile was collected continuously during the procedure and analyzed using proton nuclear magnetic resonance spectroscopy. RESULTS: The IR group had decreased COX activity and tissue oxygenation represented by deoxyhemoglobin, oxyhemoglobin, COX, and elevated redox ratios of lactate/pyruvate and ß-hydroxybutarate/acetoacetate in vivo and a decrease in COX and CS activity in vitro. The IPC + IR group showed higher levels of all measured parameters in vivo and showed a smaller decrease in COX and CS activity in vitro. CONCLUSION: This study shows that IRI affects COX activity in fatty livers. This is attenuated by IPC.