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The method of transecting the pancreatic parenchyma during pancreatic resection may influence the rate of complications, including pancreatic fistula and bleeding. The objective of this study was to compare the transection of the pancreatic parenchyma during pancreatoduodenectomy with monopolar electrocautery versus scalpel in terms of postoperative complications. A retrospective analysis of patients with open pancreatoduodenectomy from the German DGAV StuDoQ|Pancreas registry (January 2013 to December 2021) was performed. Transection of the pancreatic parenchyma with a scalpel versus monopolar electrocautery was compared regarding postoperative pancreatic fistula B/C, post-pancreatectomy hemorrhage B/C, and major complications (Clavien–Dindo classification ≥3) rates. Multivariable analysis with adjustment for potential confounders and surgical center cluster effect was performed. Overall, 6,752 patients were included in the study. In 4,072 (60.3%), transection was performed with a scalpel and, in 2,680 (39.7%), with electrocautery. Transection with electrocautery was associated with higher postoperative pancreatic fistula B/C (15.4% vs 12.8%; P =.003), post-pancreatectomy hemorrhage B/C (11% vs 7.4%; P <.001), and major complications (33.4% vs 29.6%; P =.001) rates. In the multivariable analysis, after adjustment for potential confounders and surgical center, the association of the transection method with postoperative pancreatic fistula B/C (odds ratio = 1.01; 95% CI, 0.79–1.2; P =.962), post-pancreatectomy hemorrhage B/C (odds ratio = 1.23; 95% CI, 0.94–1.6; P =.127), and major complications (odds ratio = 1.09; 95% CI, 0.93–1.27; P =.297) was not significant. The study found no significant association between transection of the pancreatic parenchyma during open pancreatoduodenectomy with a scalpel compared with monopolar electrocautery regarding pancreatic fistula, postoperative bleeding, or overall major complication rates. [ABSTRACT FROM AUTHOR]

Abstract Background Postoperative pancreatic fistula (POPF) is a major factor for morbidity and mortality after pancreatic resection. Risk stratification for POPF is important for adjustment of treatment, selection of target groups in trials and quality assessment in pancreatic surgery. In this study, we built a risk-prediction model for POPF based on a large number of predictor variables from the German pancreatic surgery registry StuDoQ|Pancreas. Methods StuDoQ|Pancreas was searched for patients, who underwent pancreatoduodenectomy from 2014 to 2016. A multivariable logistic regression model with elastic net regularization was built including 66 preoperative und intraoperative parameters. Cross-validation was used to select the optimal model. The model was assessed via area under the ROC curve (AUC) and calibration slope and intercept. Results A total of N = 2488 patients were included. In the optimal model the predictors selected were texture of the pancreatic parenchyma (soft versus hard), body mass index, histological diagnosis pancreatic ductal adenocarcinoma and operation time. The AUC was 0.70 (95% CI 0.69–0.70), the calibration slope 1.67 and intercept 1.12. In the validation set the AUC was 0.65 (95% CI 0.64–0.66), calibration slope and intercept were 1.22 and 0.42, respectively. Conclusion The model we present is a valid measurement instrument for POPF risk based on four predictor variables. It can be applied in clinical practice as well as for risk-adjustment in research studies and quality assurance in surgery. [ABSTRACT FROM AUTHOR]

Background: Pancreatic ductal adenocarcinoma (PDAC) is characterized by an aggressive biology and poor prognosis. Experimental evidence has suggested a role for the transcriptional repressor Zinc finger E-box binding homeobox 1 (ZEB1) in epithelial-mesenchymal transition, invasion, and metastasis in PDAC. ZEB1 expression has been observed in cancer cells as well as stromal fibroblasts. Our study aimed to evaluate the prognostic value of ZEB1 expression in PDAC tissue. Methods: Patient baseline and follow-up data were extracted from a prospectively maintained database. After clinicopathologic re-review, serial sliced tissue slides were immunostained for ZEB1, E-cadherin, vimentin, and pan-cytokeratin. ZEB1 expression in cancer cells and adjacent stromal fibroblasts was graded separately and correlated to routine histopathologic parameters and survival after resection. Results: A total of 117 cases of PDAC were included in the study. High ZEB1 expression in cancer cells and in stromal cancer-associated fibroblasts was associated with poor prognosis. There was also a trend for poor prognosis with a lymph node ratio of greater than 0.10. In line with its role as an inducer of epithelial-mesenchymal transition, ZEB1 expression in cancer cells was positively correlated with Vimentin expression and negatively with E-Cadherin expression. In multivariate analysis, stromal ZEB1 expression grade was the only independent factor of survival after resection. Conclusion: Our data suggest that ZEB1 expression in cancer cells as well as in stromal fibroblasts are strong prognostic factors in PDAC. Stromal ZEB1 expression is identified for the first time as an independent predictor of survival after resection of PDAC. This observation suggests that therapies targeting ZEB1 and its downstream pathways could hit both cancer cells and supporting cancer-associated fibroblasts. [Copyright &y& Elsevier]

Background: Treatment with histone deacetylases inhibitors (HDACi) such as valproic acid (VPA) and suberoylanilide hydroxamic acid (SAHA) has been shown to improve survival after lethal insults through mechanisms that are incompletely understood. Cell survival under adverse conditions requires a healthy network of capillaries to ensure adequate oxygen delivery. Angiogenic activation of endothelial cells to migrate and form sprouts is associated with characteristic changes in gene expression profiles. Because HDACi can modulate expression of various genes involved in angiogenic activity, we investigated the effect of these agents on capillary-like sprout formation in this study. Methods: Human umbilical vein endothelial cells (HUVECs) were cultured as multicellular spheroids within a type I collagen matrix, which promotes formation of sprouts resembling angiogenesis in vitro. HUVECs were cultured as multicellular spheroids within a type I collagen matrix, which promotes formation of sprouts (in vitro angiogenesis). Cells were cultured under the following conditions: Control (no growth factors); VPA (1 mmol/L); vascular endothelial growth factor (VEGF; 10 ng/mL); VPA + VEGF; SAHA (5 mmol/L), and SAHA + VEGF. After 24 hours of treatment, the length of spheroid sprouting and cell migration was assessed quantitatively. The levels of acetylated histone H3, phosphor–extracellular signal-regulated kinase (ERK)1/2, and β-catenin in HUVECs were measured by Western blotting at 6 hours after treatment. Results: High levels of acetylated histone H3 were detected in VPA and SAHA treated-groups. Compared with the VEGF-alone treated group (2379 ± 147.1 μm), the spheroid sprouting was 1.7 times increased with VPA and VEGF combined treatment (3996 ± 192.5 μm; P < .01). Cell migrations did not show a significant difference after addition of VPA, whereas SAHA suppressed migration. Expression of β-catenin was significantly increased by VPA and SAHA treatments. Addition of VPA greatly enhanced expression of phosphor-ERK1/2. Conclusion: Exposure of HUVECs to VPA and SAHA increased the expression of β-catenin and enhanced spheroid sprout formation in vitro. Modulation of HDAC-dependent pathways may offer a novel approach to alter angiogenic processes and provide a useful therapeutic target. [Copyright &y& Elsevier]

Introduction: Pancreatic intraductal papillary mucinous neoplasms (IPMN) are now identified with increasing frequency. The detection of carcinoma in IPMN is difficult and suffers from high false-positive and false-negative rates, often resulting in inappropriate treatment decisions. Improved detection of malignancy using novel biomarkers may therefore improve diagnostic accuracy. One such promising novel biomarker is Plectin-1 (Plec-1).Methods: Using immunohistochemistry, Plec-1 expression was assayed in benign (low and moderate dysplasia, n = 6) as well as malignant IPMN (high-grade dysplasia and invasive carcinoma, n = 31) and lymph node metastases from carcinoma arising in IPMN (n = 12). Furthermore, cyst fluids from benign (n = 3) and malignant IPMN (n = 4) were evaluated for Plec-1 expression.Results and Discussion: Twenty-six of 31 malignant IPMN and all 12 lymph node metastases were Plec-1 positive. In contrast, only one of six benign IPMN expressed Plec-1. The specificity of Plec-1 in distinguishing malignant IPMN from benign IPMN was 83% and its sensitivity 84%. Furthermore, all (four out of four) cyst fluids from malignant IPMN, but none of the three benign IPMN, were Plec-1 positive. These data support Plec-1 as an excellent biomarker for the early detection of carcinoma arising in IPMN. [ABSTRACT FROM AUTHOR]

Background: A “step-up” approach is currently the treatment of choice for acute necrotizing pancreatitis. Our aim was to evaluate the outcome of minimally invasive retroperitoneal necrosectomy (MINE) and endoscopic transgastric necrosectomy (ETG) and to compare it to open necrosectomy (ONE). Methods: Patients with acute pancreatitis admitted to our institution from 1998 to 2010 (n = 334) were identified. From these, patients who underwent either ONE, MINE, or ETG were selected for further analysis. Statistical analysis employed 2-sided Fisher''s exact test and Mann–Whitney U-test. Results: From 2002 to 2010, 32 patients with acute necrotizing pancreatitis were treated by minimally invasive procedures including MINE (n = 14) and ETG (n = 18) or with the classic technique of ONE (n = 30). Time from onset of symptoms to intervention was less for ONE than for MINE or ETG (median, 11 vs 39 vs 54 days; P < .05). The rate of critically ill patients with sepsis or septic shock was greatest in ONE (93%) and MINE (71%) compared with ETG (17%; P < .05). Problems after ONE and MINE were ongoing sepsis (ONE 73% vs MINE 29% vs ETG 11%) and bleeding requiring intervention (ONE 26% vs MINE 21% vs ETG 17%). A specific complication of ETG was gastric perforation into the peritoneal cavity during the procedure (28%), requiring immediate open pseudocystogastrostomy. Laparotomy was necessary in 21% after MINE and 28% after ETG owing to specific complications or persistent infected necrosis. Overall mortality was greatest after ONE (ONE 63% vs MINE 21% vs ETG 6%; P < .05). Conclusion: Morbidity and mortality remains high in acute necrotizing pancreatitis. Operative procedures should be delayed as long as possible to decrease morbidity and mortality. Minimally invasive procedures can avoid laparotomy, but also introduce specific complications requiring immediate or secondary open operative treatment. Minimally invasive procedures require unique expertise and therefore should only be performed at specialized centers. [Copyright &y& Elsevier]

Various technologies exist to remove surgical smoke. Despite high significance in surgical practice, comparative in-vivo performance data are missing. The performance of five smoke management technologies (venting, passive filtering, active filtering, circular filtration, electrostatic precipitation) was analysed in-vivo by three different laparoscopic interventions (cholecystectomy, atypic liver resection, colon surgery) with high-energy surgical instruments. Surgical smoke formation/evacuation was characterised by various aerosol-analytical instruments. In addition, operational parameters like CO 2 consumption and capnoperitoneal pressure were determined. The half-life of particle concentration was found to be a suitable parameter to describe smoke elimination efficacy and varied between (10 - 45) s. It is shown that the efficacy of smoke elimination technologies based on particle removal by evacuation can also be predicted by simple equations. Furthermore, it was found that the combination of surgical cutter and tissue defines charge and polarity of surgical smoke that influences especially the efficacy of electrostatic precipitation. Depending on the smoke elimination technology, the CO 2 consumption varied between (0.5 - 16) L/min, the capnoperitoneal stability between (2 - 17) %. Each smoke elimination technology showed advantages and disadvantages. Simple charcoal filters rapidly degrade and should be exchanged regularly during surgery. Active filtering is efficient for smoke management, but the unstable capnoperitoneum interferes with surgery. Circular filtration forms a stable capnoperitoneum, but the valveless trocar promotes relevant levels of smoke release into the environment. Electrostatic precipitation was found to be most efficient for smoke management with minimal CO 2 consumption and highly-stable capnoperitoneum. • Exposure of surgical staff by surgical smoke during laparoscopic surgery is an issue. • Surgical smoke management technologies exist, but no comparative performance data. • Five surgical smoke management technologies were comparative characterised in-vivo. • Particle concentration half-life is a suitable descriptive performance parameter. • Electrostatic precipitation is more efficient than steady carbon dioxide exchange. [ABSTRACT FROM AUTHOR]

Distal cholangiocarcinoma (DCC) is a rare malignancy and validated prognostic markers remain scarce. We aimed to evaluate the role of serum CA19-9 as a potential biomarker in DCC. Patients operated for DCC at 6 high-volume surgical centers from 1994 to 2015 were identified from prospectively maintained databases. Patient baseline characteristics, surgical and histopathological parameters, as well as overall survival after resection were assessed for correlation with preoperative bilirubin-adjusted serum carbohydrate antigen 19-9 (CA19-9). Preoperative CA19-9 to bilirubin ratio (CA19-9/BR) was classified as elevated (≥ 25 U/ml/mg/dl) according to the upper serum normal values of CA19-9 (37 U/ml) and bilirubin (1.5 mg/dl) giving a cut-off at ≥ 25 U/ml/mg/dl. In total 179 patients underwent resection for DCC during the study period. High preoperative CA19-9/BR was associated with advanced age and regional lymph node metastases. Median overall survival after resection was 27 months. Elevated preoperative serum CA19-9/bilirubin ratio (HR 1.6, p = 0.025), T3/4 stage (HR 1.8, p = 0.022), distant metastasis (HR 2.5, p = 0.007), tumor grade (HR 1.9, p = 0.001) and R status (HR 1.7, p = 0.023) were identified as independent negative prognostic factors following multivariable analysis. Elevated preoperative bilirubin-adjusted serum CA19-9 correlates with regional lymph node metastases and constitutes a negative independent prognostic factor after resection of DCC. [ABSTRACT FROM AUTHOR]

Background Mesenterico-portal vein resection (PVR) during pancreatoduodenectomy for pancreatic head cancer was established in the 1990s and can be considered a routine procedure in specialized centers today. True histopathologic portal vein invasion is predictive of poor prognosis. The aim of this study was to examine the relationship between mesenterico-portal venous tumor infiltration (PVI) and features of aggressive tumor biology. Methods Patients receiving PVR for pancreatic ductal adenocarcinoma of the pancreatic head were identified from a prospectively maintained database. Immunohistochemical staining of tumor tissue was performed for the markers of epithelial–mesenchymal transition (EMT) E-Cadherin, Vimentin and beta-Catenin. Morphology of cancer-associated fibroblasts (CAFs) was assessed as inactive or activated. Statistical calculations were performed with MedCalc software. Results In total, 41 patients could be included. Median overall survival was 25 months. PVI was found in 17 patients (41%) and was significantly associated with loss of membranous E-Cadherin in tumor buds (p = 0.020), increased Vimentin expression (p = 0.03), activated CAF morphology (p = 0.046) and margin positive resection (p = 0.005). Conclusion Our findings suggest that PVI is associated with aggressive tumor biology and disseminated growth less amenable to margin-negative resection. [ABSTRACT FROM AUTHOR]