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Background Pancreatic ductal adenocarcinoma (PDAC) is an aggressive gastrointestinal malignancy characterized by early loco-regional invasion. Portal vein resection (PVR) during pancreatoduodenectomy (PD) for PDAC is performed if tumor cell invasion to the venous wall (PVI) is suspected. The aim of this study is to evaluate radiological criteria for predicting PVR and PVI. Methods Patients undergoing PD for PDAC were identified from a prospectively maintained database. On the basis of CT- and MRI-based imaging portal vein tumor contact (PV), stranding of the superior mesenteric artery (SMA) and any alterations of the superior mesenterico-portal vein (SMPV) were evaluated. The accuracy of PVI and PVR prediction based on the radiological parameters was calculated. Results 143 patients were included in the study. 48 patients underwent PVR (34%), PVI was diagnosed in 23 patients (16%). Median overall survival was 22 months. Prediction of PVR (sensitivity 79%, negative predictive value 88%, p = 0.010) and PVI (sensitivity 95%, negative predictive value 99%, p = 0.002) was most accurate for any SMPV alterations as compared to the other radiological parameters. SMPV alterations qualified as an independent prognostic parameter (26.5 months vs. 33.5months, p = 0.034). Conclusion Radiological evaluation of any SMPV alterations is a simple preoperative method to accurately predict PVI. Assessing SMPV alterations may help to identify candidates for neoadjuvant therapy.

Acute pancreatitis (AP) is one of the most common gastrointestinal diseases and remains a life-threatening condition. Although AP resolves to restitutio ad integrum in approximately 80% of patients, it can progress to necrotizing pancreatitis (NP). NP is associated with superinfection in a third of patients, leading to an increase in mortality rate of up to 40%. Accurate and early diagnosis of NP and associated complications, as well as state-of-the-art therapy are essential to improve patient prognoses. The emerging role of endoscopy and recent trials on multidisciplinary management of NP established the "step-up approach". This approach starts with endoscopic interventions and can be escalated to other interventional and ultimately surgical procedures if required. Studies showed that this approach decreases the incidence of new multiple-organ failure as well as the risk of interventional complications. However, the optimal interventional sequence and timing of interventional procedures remain controversial. This review aims to summarize the indications, timing, and treatment outcomes for infected NP and to provide guidance on multidisciplinary decision-making.

The benefit of adjuvant therapy in ampullary cancer (AMPAC) patients following pancreatoduodenectomy (PD) is debated. The aim of this study was to determine the role of adjuvant therapy after pancreatoduodenectomy (PD) in histological subtypes of AMPAC.Patients undergoing PD for AMPAC at 5 high-volume European surgical centers from 1996 to 2017 were identified. Patient baseline characteristics, surgical and histopathological parameters, and long-term overall survival (OS) after resection were evaluated.214 patients undergoing PD for AMPAC were included. ASA score (ASA1-2 149 vs. ASA 3-4 82 months median OS, p = 0.002), preoperative serum CEA (CEA0.5 ng/ml 128 vs. CEA0.5 ng/ml 62 months, p = 0.013), preoperative serum CA19-9 (CA19-9 40 IU/ml 147 vs. CA19-940IU/ml 111 months, p = 0.042), T stage (T1-2 163 vs. T3-4 98 months, p 0.001), N stage (N0 159 vs. N+ 110 months, p 0.001), grading (G1-2 145 vs. G3-4 113 months, p = 0.026), R status (R0 136 vs. R+ 38 months, p = 0.031), and histological subtype (intestinal subtype 156 vs. PB/M subtype 118 months, p = 0.003) qualified as prognostic parameters. In multivariable analysis, ASA score (HR 1.784, 95%CI 0.997-3.193, p = 0.050) and N stage (HR 1.831, 95%CI 0.904-3.707, p = 0.033) remained independent prognostic factors. In PB/M subtype AMPAC, patients undergoing adjuvant therapy showed an improved median overall survival (adjuvant therapy 85 months vs. no adjuvant therapy 65 months, p = 0.005), and adjuvant therapy remained an independent prognostic parameter in multivariate analysis (HR 0.351, 95%CI 0.151-0.851, p = 0.015). There was no significant benefit of adjuvant therapy in intestinal subtype AMPAC patients.Adjuvant treatment seems indicated in pancreatobiliary or mixed type AMPAC.

Background 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. Methods 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. Results 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. Conclusion Elevated preoperative bilirubin-adjusted serum CA19-9 correlates with regional lymph node metastases and constitutes a negative independent prognostic factor after resection of DCC.

Background/Objective The impact of preoperative biliary stenting (PBS) before pancreatoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC) is controversial. Methods Patients undergoing PD with or without PBS for PDAC were identified from the German DGAV-StuDoQlPancreas registry. The impact of PBS on perioperative complications was analyzed. Results 1133 patients undergoing PD for PDAC were identified from the registry. After matching, 480 PBS patients vs. 480 patients without PBS were analyzed. Postoperative complications Clavien-Dindo classification (CDC) grade IIIa-IVb were higher in PBS patients (PBS 27% vs. no PBS 22%, p = 0.027). 320 PBS patients (66%) had no history of jaundice. In these patients, PBS was associated with higher morbidity. In contrast, PBS was not associated with higher complication rates in patients with history of jaundice. Serum bilirubin levels of 15 mg/dl and higher lead to more CDC IIIa-IVb (24% vs. 28%, p = 0.053) and higher mortality (3% vs. 7%, p 15 mg/dl increased CDC IIa-IVb complications (21% vs. 50%, p = 0.001), mortality was equivalent. Conclusion Most PBS procedures were performed in patients with no history of jaundice and increased morbidity. Serum bilirubin levels >15 mg/dl lead to higher morbidity and mortality. PBS correlated with higher complication rates in these patients.

The ABO blood type has been associated with risk of development of several malignancies, including pancreatic cancer. Data regarding IPMN is equivocal. To investigate this further, we analyzed the association between the ABO blood group and the presence of malignancy in a large cohort of resected IPMN and its influence in survival.819 patients who underwent pancreatic resection for IPMN in the Massachusetts General Hospital (MGH) and Cambridge University Hospitals NHS Foundation Trust (CUH) from January 1993 to December 2020 were identified from prospective institutional databases. Pathological characteristics and blood type were correlated.The distribution of blood types A, B, AB and O was 384 (47%), 92 (11%), 44 (5%) and 299 (37%), respectively. This blood type distribution was different than the reference population of the MGH and the CUH, which is 55% non-O blood group, and 45% type O. There was a significant predominance of non-O blood types when compared with O-blood type in patients with malignant IPMN (i.e. patients with high-grade dysplasia and invasive cancer) (67% vs 33%, OR 1.31 95%CI: 0.98-1.75, p = 0.069). The association was stronger for IPMN with invasive cancer (OR 1.43 95%CI: 1.01-2.02, p = 0.039). Blood group did not influence survival.Non-O blood type is associated with need for resection in IPMN and with presence of invasive carcinoma.

Background The present study aimed to examine the impact of microscopically tumour-infiltrated resection margins (R1) in pancreatic ductal adenocarcinoma (PDAC) patients with advanced lymphonodular metastasis (pN1–pN2) on overall survival (OS). Methods This retrospective, multi-institutional analysis included patients undergoing surgical resection for PDAC at three tertiary university centres between 2005 and 2018. Subcohorts of patients with lymph node status pN0–N2 were stratified according to the histopathological resection status using Kaplan-Meier survival analysis. Results The OS of the entire cohort (n = 620) correlated inversely with the pN status (26 [pN0], 18 [pN1], 11.8 [pN2] months, P < 0.001) and R status (21.7 [R0], 12.5 [R1] months, P < 0.001). However, there was no statistically significant OS difference between R0 versus R1 in cases with advanced lymphonodular metastases: 19.6 months (95% CI: 17.4–20.9) versus 13.6 months (95% CI: 10.7–18.0) for pN1 stage and 13.7 months (95% CI: 10.7–18.9) versus 10.1 months (95% CI: 7.9–19.1) for pN2, respectively. Accordingly, N stage–dependent Cox regression analysis revealed that R status was a prognostic factor in pN0 cases only. Furthermore, there was no significant survival disadvantage for patients with R0 resection but circumferential resection margin invasion (≤ 1 mm; CRM+; 10.7 months) versus CRM-negative (13.7 months) cases in pN2 stages (P = 0.5). Conclusions An R1 resection is not associated with worse OS in pN2 cases. If there is evidence of advanced lymph node metastasis and a re-resection due to an R1 situation (e.g. at venous or arterial vessels) may substantially increase the perioperative risk, margin clearance in order to reach local control might be avoided with respect to the OS.

Background Postoperative pancreatic fistula (POPF) after pancreatoduodenectomy (PD) can be associated with severe postoperative morbidity. This study aims to develop a preoperative POPF risk calculator that can be easily implemented in clinical routine. Methods Patients undergoing PD were identified from a prospectively-maintained database. A total of 11 preoperative baseline and CT-based radiological parameters were used in a binominal logistic regression model. Parameters remaining predictive for grade B/C POPF were entered into the risk calculator and diagnostic accuracy measures and ROC curves were calculated for a training and a test patient cohort. The risk calculator was transformed into a simple nomogram. Results A total of 242 patients undergoing PD in the period from 2012 to 2018 were included. CT-imaging-based maximum main pancreatic duct (MPD) diameter (p = 0.047), CT-imaging-based pancreatic gland diameter at the anticipated resection margin (p = 0.002) and gender (p = 0.058) were the parameters most predictive for grade B/C POPF. Based on these parameters, a risk calculator was developed to identify patients at high risk of developing grade B/C POPF. In a training cohort of PD patients this risk calculator was associated with an AUC of 0.808 (95%CI 0.726–0.874) and an AUC of 0.756 (95%CI 0.669-0-830) in the independent test cohort. A nomogram applicable as a visual risk scale for quick assessment of POPF grade B/C risk was developed. Conclusion The preoperative POPF risk calculator provides a simple tool to stratify patients planned for PD according to the risk of developing postoperative grade B/C POPF. The nomogram visual risk scale can be easily integrated into clinical routine and may be a valuable model to select patients for POPF-preventive therapy or as a stratification tool for clinical trials.

OBJECTIVE Our aim was to evaluate recurrence patterns of surgically resected PDAC patients with negative (pN0) or positive (pN1) lymph nodes. SUMMARY BACKGROUND DATA Pancreatic ductal adenocarcinoma (PDAC) is predicted to become the second leading cause of cancer death by 2030. This is mostly due to early local and distant metastasis, even after surgical resection. Knowledge about patterns of recurrence in different patient populations could offer new therapeutic avenues. METHODS Clinicopathologic data were collected for 546 patients who underwent resection of their PDAC between 2005 and 2016 from 2 tertiary university centers. Patients were divided into an upfront resection group (n = 394) and a neoadjuvant group (n = 152). RESULTS Tumor recurrence was significantly less common in pN0 patients as compared with pN1 patients, (upfront surgery: 55% vs. 77%, P < 0.001 and 64% vs. 78%, P = 0.040 in the neoadjuvant group). In addition, time to recurrence was significantly longer in pN0 versus pN1 patients in the upfront resected patients (median 16 mo pN0 vs. 10 mo pN1 P < 0.001), and the neoadjuvant group (pN0 21 mo vs. 11 mo pN1, P < 0.001). Of the patients who recurred, 62% presented with distant metastases (63% of pN0 and 62% of pN1, P = 0.553), 24% with local disease (27% of pN0 and 23% of pN1, P = 0.672) and 14% with synchronous local and distant disease (10% of pN0 and 15% of pN1, P = 0.292). Similarly, there was no difference in recurrence patterns between pN0 and pN1 in the neoadjuvant group, in which 68% recurred with distant metastases (76% of pN0 and 64% of pN1, P = 0.326) and 18% recurred with local disease (pN0: 22% and pN1: 15%, P = 0.435). CONCLUSION Time to recurrence was significantly longer for pN0 patients. However, patterns of recurrence for pN0 vs. pN1 patients were identical. Lymph node status was predictive of time to recurrence, but not location of recurrence.

Whether patients who undergo resection of ampullary adenocarcinoma have a survival benefit from adjuvant chemotherapy is currently unknown. The aim of this study was to compare survival between patients with and without adjuvant chemotherapy after resection of ampullary adenocarcinoma in a propensity score-matched analysis.An international multicentre cohort study was conducted, including patients who underwent pancreatoduodenectomy for ampullary adenocarcinoma between 2006 and 2017, in 13 centres in six countries. Propensity scores were used to match patients who received adjuvant chemotherapy with those who did not, in the entire cohort and in two subgroups (pancreatobiliary/mixed and intestinal subtypes). Survival was assessed using the Kaplan-Meier method and Cox regression analyses.Overall, 1163 patients underwent pancreatoduodenectomy for ampullary adenocarcinoma. After excluding 187 patients, median survival in the remaining 976 patients was 67 (95 per cent c.i. 56 to 78) months. A total of 520 patients (53·3 per cent) received adjuvant chemotherapy. In a propensity score-matched cohort (194 patients in each group), survival was better among patients who received adjuvant chemotherapy than in those who did not (median survival not reached versus 60 months respectively; P = 0·051). A survival benefit was seen in patients with the pancreatobiliary/mixed subtype; median survival was not reached in patients receiving adjuvant chemotherapy and 32 months in the group without chemotherapy (P = 0·020). Patients with the intestinal subtype did not show any survival benefit from adjuvant chemotherapy.Patients with resected ampullary adenocarcinoma may benefit from gemcitabine-based adjuvant chemotherapy, but this effect may be reserved for those with the pancreatobiliary and/or mixed subtype.Actualmente se desconoce si la quimioterapia adyuvante ofrece un beneficio en la supervivencia de los pacientes que se someten a resección de un adenocarcinoma ampular. El objetivo de este estudio fue comparar la supervivencia mediante la concordancia estimada por emparejamiento por puntaje de propensión, entre pacientes con y sin quimioterapia adyuvante después de la resección de un adenocarcinoma ampular. MÉTODOS: Se realizó un estudio internacional de cohortes multicéntrico, que incluyó a los pacientes que se sometieron a una duodenopancreatectomía por adenocarcinoma ampular (2006-2017) en 13 centros de seis países. Los puntajes de propensión se usaron para emparejar a los pacientes que recibieron quimioterapia adyuvante con los que no; tanto en la cohorte completa como en dos subgrupos (subtipo pancreaticobiliar / mixto e intestinal). La supervivencia se evaluó utilizando el método de Kaplan-Meier y las regresiones de Cox.En total, 1.163 pacientes fueron sometidos a una duodenopancreatectomía por adenocarcinoma ampular. Después de excluir a 179 pacientes, la mediana de supervivencia de los 976 pacientes restantes fue de 67 meses (i.c. del 95%, 56-78), de los cuales un total de 520 pacientes (53%) recibieron quimioterapia adyuvante. En una cohorte de emparejamiento por puntaje de propensión (194 versus 194 pacientes), la mediana de supervivencia fue mejor en los pacientes tratados con quimioterapia adyuvante en comparación con aquellos sin quimioterapia adyuvante (no se alcanzó la mediana de supervivencia versus 60 meses, respectivamente; P = 0,051). En el subtipo pancreaticobiliar/mixto se observó un beneficio en la supervivencia; no se alcanzó la mediana de supervivencia en pacientes que recibieron quimioterapia adyuvante versus 32 meses en el grupo sin quimioterapia, P = 0,020. El subtipo intestinal no mostró beneficio en la supervivencia de la quimioterapia adyuvante. CONCLUSIÓN: Los pacientes con adenocarcinoma ampular resecado pueden beneficiarse de la quimioterapia adyuvante basada en gemcitabina, pero este efecto podría reservarse para aquellos pacientes con subtipo de tumor pancreaticobiliar y/o mixto.

Objective To describe our institutional experience with resected cystic tumors of the pancreas with emphasis on changes in clinical presentation and accuracy of preoperative diagnosis. Summary background data Incidental-discovery of pancreatic cystic lesions has increased and has led to a rise in pancreatic resections. It is important to analyze surgical outcomes from these procedures, and the prevalence of malignancy, pre-malignancy and resections for purely benign lesions, some of which may be unintended. Methods Retrospective review of a prospective database spanning 3 decades. Presence of symptoms, incidental discovery, diagnostic studies, type of surgery, postoperative outcomes, and concordance between presumptive diagnosis and final histopathology were recorded. Results 1290 patients were identified, 62% female with mean age of 60 y. 57% of tumors were incidentally-discovered. 90-day operative mortality was 0.9% and major morbidity 14.4%. There were 23 different diagnosis, but IPMN, MCN and serous cystadenoma comprised 80% of cases. Concordance between preoperative and final histopathological diagnosis increased by decade from 45%, to 68%, and is currently 80%, rising in parallel with the use of EUS, cytology and molecular analysis. The addition of molecular analysis improved accuracy to 91%. Of mis-diagnosed cases, half were purely benign and taken to surgery with the presumption of malignancy or premalignancy. The majority of these were serous cystadenomas. Conclusions Indications and diagnostic work-up of cystic tumors of the pancreas have changed over time. Surgical resection can be performed with very low mortality and acceptable morbidity and diagnostic accuracy is currently 80%. About 10% of patients are still undergoing surgery for purely benign lesions that were presumed to be malignant or premalignant. Further refinements in diagnostic tests are required to improve accuracy.

Surgically assessed pancreatic texture has been identified as the strongest predictor of postoperative pancreatic fistula. However, texture is a subjective parameter with no proven reliability or validity. Therefore, a more objective parameter is needed. In this study, we evaluated the fibrosis level at the pancreatic neck resection margin and correlated fibrosis and all clinico-pathologic parameters collected over the course of the Pancreatogastrostomy vs Pancreatojejunostomy for RECOnstruction (RECOPANC) study.The RECOPANC trial was a multicenter randomized prospective trial of patients undergoing pancreatoduodenectomy. There were 261 hematoxylin and eosin-stained slides allocated for histopathologic analyses. Pancreatic fibrosis was scored from 0 to III (no fibrosis up to severe fibrosis) by 2 blinded independent pathologists. All variables possibly associated with POPF were entered into a generalized linear model for multivariable analysis.The fibrosis grade and pancreatic texture were scored in all 261 patients. In POPF B/C (postoperative pancreatic fistula grade B or C) patients, 71% had a soft pancreas, and fibrosis grades were distributed as follows: 48% with score 0, 28% with score I, 20% with score II, and 7% with score III, respectively. Fibrosis grading showed substantial inter-rater reliability (kappa = 0.74) and correlated positively with hard pancreatic texture (p0.05). In univariable analysis, area under the curve (AUC) for POPF B/C prediction was higher for fibrosis grade than for pancreatic texture (0.71 vs 0.59). In multivariate analysis, the following predictors were selected: sex, surgeon volume, pancreatic texture, and fibrosis grade. However, the addition of pancreatic texture only led to an incremental improvement (AUC 0.794 vs 0.819).Histologically evaluated pancreatic fibrosis is an easily applicable and highly reproducible POPF predictor and superior to surgically evaluated pancreatic texture. Future studies might use fibrosis grade for risk stratification in pancreatoduodenectomy.

Background: Biliary stenting leads to antimicrobial-resistant (AMR) microorganism retrievement in bile cultures. However, the impact of intraoperative bile colonizations on post-pancreaticoduodenectomy complications remains unclear. Aims of our study were to characterize the bile flora of stented patients in comparison with postoperative cultures and to analyze whether patterns of drug resistance affected postoperative outcomes. Methods: We analyzed records from stent-bearing pancreaticoduodenectomy patients at 3 European centers. Intra- and postoperative cultures were compared and classified as multidrug sensitive (MDS), multidrug resistant (MDR), and extensively drug resistant (XDR). Thirty-day complications were graded according to international standards. Results: Out of 270 patients, intraoperative cultures were positive in 219 (81.1%) cases. In 36.7%, MDS species were isolated; in 35.9%, MDR; and in 8.5%, XDR species. A solid correspondence between the species isolated intra- and postoperatively (p< 0.001) was observed. Intraoperative MDR/XDR isolation was associated with an increased rate of surgical (p= 0.043) and infectious complications (p= 0.030), but not severe complication rate (p = 0.973). Postoperative MDR/XDR isolation was associated with higher risk of major complications (45.6% vs. 15.8%, p< 0.001), postoperative pancreatic fistula (p< 0.001), and post-pancreatectomy hemorrhage (p= 0.002). By multivariate analysis, intraoperative AMR isolation was associated with high likelihood of postoperative AMR infections. However, only in 43/121 cases, intraoperative MDR/XDR microorganisms turned into the occurrence of postoperative infections. Conclusion: Intraoperative AMR isolates do not translate into severe outcomes, despite being significantly associated with surgical and infectious complications.

Background: Borderline resectability in pancreatic cancer (PDAC) is currently debated. Methods: Patients undergoing pancreatic resections for PDAC were identified from a prospectively maintained database. As new borderline criteria, the presence of any superior mesenterico-portal vein alteration (SMPV) and perivascular stranding of the superior mesenteric artery (SMA) was evaluated in preoperative imaging. The accuracy of established radiological borderline criteria as compared to the new borderline criteria in predicting R status (sensitivity/negative predictive value) and overall survival was assessed. Results: 118 patients undergoing pancreatic resections for PDAC from 2013 to 2018 were identified. Forty-three (36.4%) had radiological perivascular SMA stranding and 55 (46.6%) had SMPV alterations. Interrater reliability was 90% for SMA stranding and 87% for SMPV alterations. The new borderline definition including SMPV alterations and perivascular SMA stranding was the best predictor of conventional R status (p = 0.040, sensitivity 53%, negative predictive value 81%) and Leeds/Wittekind circumferential margin status (p = 0.050, sensitivity 73%, negative predictive value 79%) as compared to established borderline resectability definition criteria. Perivascular SMA stranding qualified as an independent negative prognostic parameter (HR 3.066, 95% CI 1.078–5.716, p = 0.036). Conclusion: The radiological evaluation of any SMPV alteration and perivascular SMA stranding predicts R status and overall survival in PDAC patients, and may serve to identify potential candidates for neoadjuvant therapy.

Pancreatoduodenectomy (PD) with superior mesenteric/portal venous resection (PVR) for pancreatic ductal adenocarcinoma (PDAC) is performed routinely in case of tumor adhesion to the superior mesenteric or portal vein. True histopathological portal vein invasion (PVI) is found in a subgroup of patients. Even though this procedure has become routine in most centers for pancreatic surgery, data on prognostic factors in this situation is limited. The aim of this study was to identify prognostic factors after PD with PVR for PDAC. Retrospective analysis was performed on the basis of a prospectively maintained database, and paraffin-embedded formalin-fixed tissue slides stained for hematoxylin-eosin were re-evaluated by two independent pathologists. Statistical analysis was conducted using MedCalc software. From 2001 to 2012, 86 cases of PD with PVR for PDAC with long-term follow-up and sufficient tissue for re-assessment were identified. Histopathological re-review disclosed PVI in 39 resection specimens and adhesion without infiltration in 47. Overall median survival in all patients was 22 months. Patients with PVI versus no PVI showed comparable baseline demographic and standard histopathological parameters; however, PVI was associated with microscopic hemangiosis (p = 0.001) and positive margin status (p = 0.001). Median survival in patients with PVI was 14 months versus 25 months in patients without PVI (p = 0.042). Only lymph node ratio and PVI were independent predictors of survival after resection. The only independent factors influencing overall survival after PD with PVR for PDAC were lymph node ratio and PVI. PVI might indicate aggressive tumor biology, but the available data remains controversial.

Pancreatoduodenectomy is the most common operative procedure performed for distal bile duct carcinoma. Data on outcome after surgery for this rare malignancy is scarce, especially from western countries. The purpose of this study is to explore the prognostic factors and outcome after pancreatoduodenectomy for distal bile duct carcinoma. Patients receiving pancreatoduodenectomy for distal bile duct carcinoma were identified from institutional databases of five German and one Russian academic centers for pancreatic surgery. Univariable and multivariable general linear model, Kaplan-Meier method, and Cox regression were used to identify prognostic factors for postoperative mortality and overall survival. N = 228 patients operated from 1994 to 2015 were included. Reoperation (OR 5.38, 95%CI 1.51–19.22, p = 0.010), grade B/C postpancreatectomy hemorrhage (OR 3.73, 95%CI 1.13–12.35, p = 0.031), grade B/C postoperative pancreatic fistula (OR 4.29, 95%CI 1.25–14.72, p = 0.038), and advanced age (OR 4.00, 95%CI 1.12–14.03, p = 0.033) were independent risk factors for in-hospital mortality in multivariable analysis. Median survival was 29 months, 5-year survival 27%. Positive resection margin (HR 2.07, 95%CI 1.29–3.33, p = 0.003), high tumor grade (HR 1.71, 95%CI 1.13–2.58, p = 0.010), lymph node (HR 1.68, 95%CI 1.13–2.51, p = 0.011), and distant metastases (HR 2.70, 95%CI 1.21–5.58, p = 0.014), as well as severe non-fatal postoperative complications (HR 1.64, 95%CI 1.04–2.58, p = 0.033) were independent negative prognostic factors for survival in multivariable analysis. Distant metastases and positive resection margin are the strongest negative prognostic factors for survival after pancreatoduodenectomy for distal bile duct carcinoma; thus, surgery with curative intent is only warranted in patients with local disease, where R0 resection is feasible.

Background/aim The role of radio(chemo) therapy for non-metastatic bile duct cancer is not well defined. This study provides additional data for this rare situation. Patients and methods Data of eight patients receiving radio(chemo)therapy for non-metastatic bile duct cancer were retrospectively analyzed regarding local control, metastases-free survival and overall survival. In addition to the entire cohort, five tumor- or treatment-related factors were investigated: tumor stage, histologic grading, point in time of radio(chemo)therapy, upfront surgery and concurrent chemotherapy. Results Median overall survival was 37 months. Overall survival rates at 3 and 5 years were 56% and 38%, respectively. Lower histologic grading was significantly associated with better overall survival (p=0.042). Metastases-free survival rates at 3 and 5 years were 38% and 19%, while local control rates were 43% and 21%, respectively. Concurrent radiochemotherapy (vs. radiotherapy alone) resulted in significantly improved local control (p=0.014). Conclusion Radiochemotherapy can achieve promising results in selected patients with non-metastatic bile duct cancer.

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.