Search

The role of parenchyma-sparing resections (PSR) and lymph node dissection in small (3 cm) nonfunctional pancreatic neuroendocrine tumors (PNET) is unlikely to be studied in a prospective randomized clinical trial. By combining data from 4 high-volume pancreatic centers we compared postoperative and long-term outcomes of patients who underwent PSR with patients who underwent oncologic resections.Retrospective review of prospectively collected clinicopathologic data of patients who underwent pancreatectomy between 2000 and 2021 was collected from 4 high-volume institutions. PSR and lymph node-sparing resections (enucleation and central pancreatectomy) were compared to those who underwent oncologic resections with lymphadenectomy (pancreaticoduodenectomy, distal pancreatectomy). Statistical testing was performed using χ 2 test and t test, survival estimates with Kaplan-Meier method and multivariate analysis using Cox proportional hazard model.Of 810 patients with small sporadic nonfunctional PNETs, 121 (14.9%) had enucleations, 100 (12.3%) had central pancreatectomies, and 589 (72.7%) patients underwent oncologic resections. The median age was 59 years and 48.2% were female with a median tumor size of 2.5 cm. After case-control matching for tumor size, 221 patients were selected in each group. Patients with PSR were more likely to undergo minimally invasive operations (32.6% vs 13.6%, P0.001), had less intraoperative blood loss (358 vs 511 ml, P0.001) and had shorter operative times (180 vs 330 minutes, P0.001) than patients undergoing oncologic resections. While the mean number of lymph nodes harvested was lower for PSR (n=1.4 vs n=9.9, P0.001), the mean number of positive lymph nodes was equivalent to oncologic resections (n=1.1 vs n=0.9, P =0.808). Although the rate of all postoperative complications was similar for PSR and oncologic resections (38.5% vs 48.2%, P =0.090), it was higher for central pancreatectomies (38.5% vs 56.6%, P =0.003). Long-term median disease-free survival (190.5 vs 195.2 months, P =0.506) and overall survival (197.9 vs 192.6 months, P =0.372) were comparable. Of the 810 patients 136 (16.7%) had no lymph nodes resected. These patients experienced less blood loss, shorter operations ( P0.001), and lower postoperative complication rates as compared to patients who had lymphadenectomies (39.7% vs 56.9%, P =0.008). Median disease-free survival (197.1 vs 191.9 months, P =0.837) and overall survival (200 vs 195.1 months, P =0.827) were similar for patients with no lymph nodes resected and patients with negative lymph nodes (N0) after lymphadenectomy.In small3 cm nonfunctional PNETs, PSRs and lymph node-sparing resections are associated with lower blood loss, shorter operative times, and lower complication rates when compared to oncologic resections, and have similar long-term oncologic outcomes.

Objective The available literature regarding outcome after pancreatic resection in locally advanced non-functional pNEN (LA-pNEN) is sparse. Therefore, this study evaluates the current survival outcomes and prognostic factors in after resection of LA-pNEN. Materials and methods This population-based analysis was derived from 17 German cancer registries from 2000 to 2019. Patients with upfront resected non-functional non-metastatic LA-pNEN were included. Results Out of 2776 patients with pNEN, 277 met the inclusion criteria. 137 (45%) of the patients were female. The median age was 63 ± 18 years. Lymph node metastasis was present in 45%. G1, G2 and G3 pNEN were found in 39%, 47% and 14% of the patients, respectively. Resection of LA-pNEN resulted in favorable 3-, 5- and 10-year overall survival of 79%, 74%, and 47%. Positive resection margin was the only potentially modifiable independent prognostic factor for overall survival (HR 1.93, 95% CI 1.71–3.69, p value = 0.046), whereas tumor grade G3 (HR 5.26, 95% CI 2.09–13.25, p value p value = 0.012) were the only independent prognostic factors for disease-free survival. Conclusion Resection of LA-pNEN is feasible and associated with favorable overall survival. G1 LA-pNEN with negative resection margins and absence of lymph node metastasis and lymphangiosis might be considered as cured, while those not fulfilling these criteria might be considered as a high-risk group for disease progression. Herein, negative resection margins represent the only potentially modifiable prognostic factor in LA-pNEN but seem to be influenced by tumor grade.

Zusammenfassung Hintergrund In den letzten Jahren haben sich Veränderungen in der Behandlung des duktalen Pankreaskarzinoms bezüglich der multimodalen Therapie und auch der chirurgischen Therapie ergeben. Diese Veränderungen sind bisher noch nicht in großen landesweiten Studien in Deutschland untersucht worden. Die vorliegende Arbeit gibt einen ersten Überblick aus chirurgischer Perspektive über die Entwicklungen in Diagnose, Therapie und Überleben des Pankreaskarzinoms innerhalb der letzten 19 Jahre in Deutschland. Methoden In dieser Kohorte aus 18 klinischen Krebsregistern Deutschlands wurden Patienten mit Diagnose eines duktalen Pankreaskarzinoms von 2000–2018 eingeschlossen. Die Patienten wurden nach Diagnosejahren (2000–2009 vs. 2010–2018) und nach Behandlungsmodalitäten aufgeteilt und verglichen. Ergebnisse In der Kohorte von ca. 48000 Patienten mit duktalem Pankreaskarzinom zeigte sich eine Erhöhung der Zahl der Neuerkrankungen von ca. 18000 auf 30000 Patienten in den beiden 10-Jahres-Abschnitten. Das mediane Gesamtüberleben stieg marginal, aber statistisch signifikant von 7,1 auf 7,9 Monate (p Zusammenfassung Die Krebsregisterdaten scheinen den bekannten Anstieg der Inzidenz des Pankreaskarzinoms in der westlichen Welt zu bestätigen. Resektionsraten sowie die Raten an Behandlung in neoadjuvanter sowie palliativer Intention erhöhten sich ebenfalls. Das Gesamtüberleben aller Patienten mit einem duktalen Pankreaskarzinom verlängerte sich allerdings nur marginal. In Subgruppen von Patienten, die in kurativer Intention behandelt wurden, zeigten sich jedoch mitunter deutlich längere Überlebenszeiten.

Background. Myocardial revascularization is a life-saving technology, which contributes to increase in lifespan, reduction in myocardial infarction recurrences and repeated surgeries along with improved life quality of the patients with coronary artery disease (CAD). Estimation of the risks, severity of coronary bed lesion, presence of concomitant diseases, and area of hibernating myocardium, as well as patient’s agreement are the basis of treatment method selection. Positive structural and functional changes in myocardium (increase in area of viable myocardium), restoration or improvement of systolic function of left ventricle (increase in ejection fraction and decrease in end-diastolic volume), reduction of angina symptoms are the expected results from the surgical treatment. Purpose – to determine the influence of risk factors for coronary artery disease on the outcome of surgical treatment by the method of aorto-coronary artery bypass grafting with the help of diagnostic evaluation of myocardial scintigraphy parameters. Materials and methods. For the implementation of the clinical objectives, 62 patients with coronary artery disease were examined. The average age of the patients was 59.6 ± 8.2 years. Myocardial scintigraphy was performed in the SPECT mode with ECG synchronization (Gated SPECT). 99mTc-MIBI with an activity of 555-740 MBq was used. Myocardial scintigraphy was conducted over time of treatment (before and after coronary artery bypass grafting) according to One Day Rest protocol. Results. The influence of risk factors was assessed using dynamic and static integral indices. The dynamic integral index didn’t reveal statistically significant risk factors: smoking (p = 0.54), left ventricular contractility impairment (p = 0.43), history of myocardial infarction (p = 0.4), stage of heart failure (p = 0.53), and functional class of angina (p = 0.08). The static integral index didn’t reveal statistically significant influence as well: smoking (p = 0.13), left ventricular contractility impairment (p = 0.58), history of myocardial infarction (p = 0.1), stage of heart failure (p = 0.11), and functional class of angina (p = 0.6). Conclusions. The studied risk factors for coronary artery disease, namely: history of myocardial infarction, left ventricular contractility impairment, stage of heart failure, functional class of angina, and smoking in the study group of patients had no registered influence on the revascularization effect by coronary artery bypass grafting method (integrated static and dynamic indices p > 0.05)., Актуальність. Користь променевої терапії (ПТ) у лікуванні раку підшлункової залози (РПЗ) залишається предметом обговорення протягом десятиліть [1]. Існує багато суперечок щодо ПТ та її комбінацій з іншими методами лікування РПЗ. Мета роботи – з’ясувати хірургічні переваги комбінованої неоад’ювантної терапії (НАТ) РПЗ із акцентом на індукцію локального фіброзу підшлункової залози та його впливу на післяопераційний стан. Вирішити питання особливої ролі ПТ при комбінованій НАТ. Згадати поточні рандомізовані контрольовані дослідження (РКД) такого напрямку. Обговорити сучасне значення стереотаксичної променевої терапії (СТПТ) у неоад’ювантному лікуванні. Матеріали та методи. З метою пошуку літератури використовували бази MEDLINE/PubMed, Scopus та Web of Science. Пошук виконувався серед англомовної літератури за такими ключовими словами: pancreatic cancer; neoadjuvant radiotherapy (NART); postoperative pancreatic fistula (POPF); pancreatic fibrosis; stereotactic body radiotherapy (SBRT). Розглядалися мета-аналізи, систематичні огляди та рандомізовані клінічні дослідження, ретроспективні дослідження. Серед 148 публікацій, що задовільнили критеріям пошуку, було відібрано 44. Дата останнього пошуку 20.02.2022. Результати та їх обговорення. Серед переваг НАТ: кращі показники дотримання режимів неоад’ювантної хіміотерапії (НАХТ) або неоад’ювантної хіміопроменевої терапії (НАХПТ), можливість вибору пацієнтів із неметастатичним захворюванням, яким може бути корисна хірургічна резекція з довготривалою виживаністю; лікування захворювання з імовірними мікрометастазами, які немає змоги виявити на початку лікування; більша ймовірність досягнення зниження ступенів T i N, збільшення частоти R0-резекції. Обговорюється питання неоад’ювантної променевої терапії (НАПТ) у контексті комбінованої НАТ РПЗ. Представлено онкологічні та хірургічні переваги даного методу. З’ясовано роль СТПТ та сучасний стан проблеми. Згадуються поточні контрольовані рандомізовані дослідження. Неоад’ювантна СТПТ після мультиагентної індукційної хіміотерапії може бути майбутнім трендом у НАПТ РПЗ. Висновки. СТПТ може бути рекомендовано для застосування у спеціалізованих центрах як ефективний метод лікування після індукційної НАХТ у хворих на неметастатичний РПЗ із судинною інвазією, без чітких ознак радіологічної відповіді та при доброму загальному стані пацієнта.

Predicting R status before surgery for pancreatic cancer (PDAC) patients with upfront surgery and neoadjuvant therapy.Negative surgical margins (R0) are a key predictor of long-term outcomes in PDAC.Patients undergoing pancreatic resection with curative intent for PDAC were identified. Using the CT scans from the time of diagnosis, the 2019 NCCN borderline resectability criteria were compared to novel criteria: presence of any alteration of the superior mesenteric-portal vein (SMPV) and perivascular stranding of the superior mesenteric artery (SMA). Accuracy of predicting R status was evaluated for both criteria. Patient baseline characteristics, surgical, histopathological parameters, and long-term overall survival (OS) after resection were evaluated.A total of 593 patients undergoing pancreatic resections for PDAC between 2010 and 2018 were identified. Three hundred and twenty-five (54.8%) patients underwent upfront surgery, whereas 268 (45.2%) received neoadjuvant therapy. In upfront resected patients, positive SMA stranding was associated with 56% margin positive resection rates, whereas positive SMA stranding and SMPV alterations together showed a margin positive resection rate of 75%. In contrast to these criteria, the 2019 NCCN borderline criteria failed to predict margin status. In patients undergoing neoadjuvant therapy, only perivascular SMA stranding remained a predictor of margin positive resection, leading to a rate of 33% R+ resections. Perivascular SMA stranding was related to higher clinical T stage (P = 0.003) and clinical N stage (P = 0.043) as well as perineural invasion (P = 0.022). SMA stranding was associated with worse survival in both patients undergoing upfront surgery (36 vs 22 months, P = 0.002) and neoadjuvant therapy (47 vs 34 months, P = 0.050).The novel criteria were accurate predictors of R status in PDAC patients undergoing upfront resection. After neoadjuvant treatment, likelihood of positive resection margins is approximately halved, and only perivascular SMA stranding remained a predictive factor.

Background/aim The impact of venous resections and reconstruction techniques on morbidity after surgery for pancreatic cancer (PDAC) remains controversial. Patients and methods A total of 143 patients receiving pancreatoduodenectomy (PD) for PDAC between 2013 and 2018 were identified from a prospective database. Morbidity and mortality after PD with tangential resection versus end-to-end reconstruction were assessed. Results Fifty-two of 143 (36.4%) patients underwent PD with portal venous resection (PVR), which was associated with longer operation times [398 (standard error (SE) 12.01) vs. 306 (SE 13.09) min, p 0.99) were not different. Tangential venous resection was associated with similar CDC grade IIIa-IV (42.9% vs. 50.0%, p=0.781) and 30-day mortality rates (3.5% vs. 4.1%, p=0.538) as segmental resection and end-to-end venous reconstruction. Conclusion Both tangential and segmental PVR appear feasible and can be safely performed to achieve negative resection margins.

Background Approximately 30-40% of pancreatoduodenectomies for adenocarcinomas result in nonpancreatic periampullary adenocarcinoma as the final diagnosis. Depending on the origin, a distinction is made between four different carcinomas with histomorphological subtypes. Objective Carcinoma location and subtype are of prognostic and therapeutic relevance; however, the preoperative differentiation is often incorrect despite modern diagnostics. Material and methods Overview of the current literature on the classification and preoperative diagnostics of periampullary adenocarcinomas. Results A precise knowledge of the papillary anatomy is necessary for the correct classification of diagnostic findings. Current studies demonstrate diagnostically valuable information from the anamnesis, imaging and endoscopy. Conclusion In ca. 70-80% of cases a correct diagnosis of the type of periampullary adenocarcinoma is possible on the basis of interdisciplinary diagnostics. This potentially enables a correspondingly individualized treatment planning in the preoperative phase.

Purpose Postoperative pancreatic fistulae (POPF) present a serious and life-threatening complication after pancreatic head resections (PD). Therefore, reliable risk stratification to identify those at risk is urgently needed. The aim of this study was to identify postoperative laboratory parameters for the prediction of POPF in the early postoperative period. Methods One hundred eighty-two patients who underwent PD from 2012 until 2017 were retrospectively analyzed. Multivariate logistic regression was performed using the GLM (general linear model) method for model building. Two nomograms were created based on the GLM models of postoperative day one and postoperative day one to five. A cohort of 48 patients operated between 2018 and 2019 served as internal validation. Results Clinically relevant pancreatic fistulae (CR-POPF) were present in 16% (n = 29) of patients. Patients with CR-POPF experienced significantly more insufficiencies of gastroenterostomies, delayed gastric emptying, and more extraluminal bleeding than patients without CR-POPF. Multivariate analysis revealed multiple postoperative predictive models, the best one including ASA, main pancreatic duct diameter, operation time, and serum lipase as well as leucocytes on day one. This model was able to predict CR-POPF with an accuracy of 90% and an AUC of 0.903. Two nomograms were created for easier use. Conclusion Clinically relevant fistula can be predicted using simple laboratory and clinical parameters. Not serum amylase, but serum lipase is an independent predictor of CR-POPF. Our simple nomograms may help in the identification of patients for early postoperative interventions.

Objectives The postoperative quality of life (QoL) after pancreatic surgery is frequently impaired. The aim of this study was to evaluate the QoL after pancreatic surgery and its influencing risk factors. Furthermore, an age-adjusted comparison with the normal population of Germany was performed. Methods A total of 94 patients were surveyed. The Short Form-36 questionnaire was sent to all patients undergoing pancreatic surgery between 2013 and 2017. All pathologies and types of pancreatic resections were included. Statistical analyses were performed, and an analysis by the Robert Koch-Institute to determine the health-related age-adjusted QoL in Germany served as control group. Results Response rate was 29%. Median time of survey was 28 months. As compared with a normative population, QoL after pancreaticoduodenectomy was significantly impaired. Distal pancreatic resection showed no significant differences. Univariate and Lasso analyses showed that the following factors had a negative impact: coronary artery disease, chronic pancreatitis, and open access. Postoperative enzyme supplementation seemed to have a positive impact. Conclusions Pancreatic surgery leads to long-lasting negative effect on QoL. Distal pancreatic resections and laparoscopic access seemed to be the best tolerated. Complications seems to have less impact, whereas maintaining exocrine and endocrine function seems to have a positive effect.

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.

Whether the presence of bacteria in the bile or postoperative infections sustained by microorganisms with different levels of drug-resistance are associated with changes in the oncologic prognosis of patients undergoing surgery for pancreatic cancer has not been thoroughly investigated. The aim was to study the association of bile contamination, postoperative infections, and multi-level resistance with long-term outcome.Prospectively maintained databases were queried for patients who underwent pancreatoduodenectomy (PD). Patients who underwent preoperative biliary stenting prior to PD and an intraoperative bile culture were included. The levels of bacterial resistance of intraoperative bile cultures and of specimens of postoperative infections were stratified into multidrug sensitive (MDS), multidrug-resistant (MDR), and extensive drug-resistant (XDR).A total of 267 patients met the inclusion criteria. The Kaplan-Meier survival curves for overall survival (OS) of patients having no bacteriobilia or positive cultures with MDS versus MDR/XDR bacteria were not statistically different (log-rank=0.9). OS of patients stratified for no postoperative infection or infections by MDS was significantly better than those having MRD/XDR isolates (log-rank=0.04). A Cox multivariate model showed that having MRD/XDR postoperative infections was and independent variable for worse OS (HR=1.227; 95%CI=1.189-1.1918; p=0.036).Postoperative drug resistant infections are a significant risk factor for poor OS after pancreatoduodenectomy for ductal adenocarcinoma.

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.

Background: Evidence on the optimal pancreatic anastomosis during pancreatoduodenectomy is inconclusive. Large multicenter and nationwide registries may provide additional insights. The study compared the practice and outcome of different pancreatic anastomoses during pancreatoduodenectomy, focusing on the rate of postoperative pancreatic fistula, in two large audits of pancreatic surgery.Methods: Posthoc analysis of patients after pancreatoduodenectomy in the Dutch Pancreatic Cancer Audit and the German DGAV StuDoQ vertical bar Pancreas registries (January 2014 to December 2017). Postoperative pancreatic fistula (International Study Group of Pancreatic Surgery B/C), postpancreatectomy hemorrhage (International Study Group of Pancreatic Surgery B/C) and Clavien-Dindo >= 3 complications rates were compared for the three most common anastomoses: duct-to-mucosa pancreatojejunostomy, non-duct-to-mucosa pancreatojejunostomy, and non-duct-to-mucosa pancreatogastrostomy. Multivariable adjustment for potential confounders was performed.Results: Overall, 6,149 patients were included. The most common anastomosis was duct-to-mucosa pancreatojejunostomy (duct-to-mucosa pancreatojejunostomy 59.8%, non-duct-to-mucosa pancreatojejunostomy 21.1%, non-duct-to-mucosa pancreatogastrostomy 12.4%). The overall postoperative pancreatic fistula rate was 14%: duct-to-mucosa pancreatojejunostomy 12.9%, non-duct-to-mucosa pancreatojejunostomy 14.4% (P = .162), non-duct-to-mucosa pancreatogastrostomy 18.3% (P < .001). The rate of postpancreatectomy hemorrhage was the lowest after duct-to-mucosa pancreatojejunostomy: duct-to-mucosa pancreatojejunostomy 6.9%, non-duct-to-mucosa pancreatojejunostomy 10% (P < .001), non-duct-to-mucosa pancreatogastrostomy 17.9% (P < .001). The rate of Clavien-Dindo >= 3 complications was the lowest after duct-to-mucosa pancreatojejunostomy: duct-to-mucosa pancreatojejunostomy 28%, non-duct-to-mucosa pancreatojejunostomy 32.7% (P = .002), non-duct-to-mucosa pancreatogastrostomy 43.1% (P < .001). In the multivariable analysis, the risk of postoperative pancreatic fistula did not differ significantly between the three anastomoses. The risk of hemorrhage (odds ratio 2.4, 95% confidence interval 1.6-3.5, P < .001) and Clavien-Dindo >= 3 (odds ratio 1.6, 95% confidence interval 1.2-2.1, P = .001) remained significantly higher only for non-duct-to-mucosa pancreatogastrostomy.Conclusion: Data from two national audits showed no difference in the risk-adjusted postoperative pancreatic fistula rate among the three most used pancreatic anastomoses during pancreatoduodenectomy. Pancreatogastrostomy was inferior to pancreatojejunostomy regarding bleeding and overall major complications. (C) 2021 Elsevier Inc. All rights reserved.

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.

Immune modulators play a crucial role in carcinogenesis and cancer progression by impairing cancer cell-targeted immune responses. T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT) regulates T-cell function and cancer cell recognition and was therefore identified as a promising target for cancer immunotherapy. TIGIT is expressed in T cells and natural killer (NK) cells and has three ligands: CD155, CD112 and CD113. CD155 binds TIGIT with the highest affinity and promotes direct and indirect downregulation of T-cell response. TIGIT signalling further inhibits NK function and secretion of proinflammatory cytokines. An association between TIGIT expression and poor survival was identified in multiple cancer entities. Blocking TIGIT with monoclonal antibodies, and a combination of TIGIT and programmed cell death protein 1 blockade in particular, prevented tumour progression, distant metastasis and tumour recurrence in in vivo models. Inhibition of TIGIT is currently evaluated in first clinical trials.

The impact of venous resections and reconstruction techniques on morbidity after surgery for pancreatic cancer (PDAC) remains controversial.A total of 143 patients receiving pancreatoduodenectomy (PD) for PDAC between 2013 and 2018 were identified from a prospective database. Morbidity and mortality after PD with tangential resection versus end-to-end reconstruction were assessed.Fifty-two of 143 (36.4%) patients underwent PD with portal venous resection (PVR), which was associated with longer operation times [398 (standard error (SE) 12.01) vs. 306 (SE 13.09) min, p0.001]. PVR was associated with longer intensive-care-unit stay (6.3 vs. 3.8 days, p=0.054); morbidity (Clavien-Dindo classification (CDC) grade IIIa-V 45.8% vs. 35.8%, p=0.279) and 30-day mortality (4.1% vs. 4.2%, p0.99) were not different. Tangential venous resection was associated with similar CDC grade IIIa-IV (42.9% vs. 50.0%, p=0.781) and 30-day mortality rates (3.5% vs. 4.1%, p=0.538) as segmental resection and end-to-end venous reconstruction.Both tangential and segmental PVR appear feasible and can be safely performed to achieve negative resection margins.

Approximately 30-40% of pancreatoduodenectomies for adenocarcinomas result in nonpancreatic periampullary adenocarcinoma as the final diagnosis. Depending on the origin, a distinction is made between four different carcinomas with histomorphological subtypes.Carcinoma location and subtype are of prognostic and therapeutic relevance; however, the preoperative differentiation is often incorrect despite modern diagnostics.Overview of the current literature on the classification and preoperative diagnostics of periampullary adenocarcinomas.A precise knowledge of the papillary anatomy is necessary for the correct classification of diagnostic findings. Current studies demonstrate diagnostically valuable information from the anamnesis, imaging and endoscopy.In ca. 70-80% of cases a correct diagnosis of the type of periampullary adenocarcinoma is possible on the basis of interdisciplinary diagnostics. This potentially enables a correspondingly individualized treatment planning in the preoperative phase.HINTERGRUND: Etwa 30–40 % der Pankreatoduodenektomien wegen Adenokarzinomen ergeben in der endgültigen Diagnostik nichtpankreane periampulläre Adenokarzinome. Je nach Ursprung unterscheidet man vier verschiedene Karzinome mit histomorphologischen Subtypen.Karzinomlokalisation und Subtyp sind von prognostischer und therapeutischer Relevanz. Die präoperative Differenzierung ist jedoch trotz moderner Diagnostik oft nicht korrekt.Übersicht über die aktuelle Literatur zur Klassifikation und präoperativen Diagnostik periampullärer Adenokarzinome.Zur korrekten Einordnung diagnostischer Befunde ist eine genaue Kenntnis der papillären Anatomie notwendig. Aktuelle Studien demonstrieren diagnostisch wertvolle Hinweise aus Anamnese, Bildgebung und Endoskopie.In ca. 70–80 % der Fälle ist eine korrekte Artdiagnose der periampullären Adenokarzinome auf Basis der interdisziplinären Diagnostik möglich. Dies ermöglicht potenziell eine entsprechend individualisierte Therapieplanung bereits präoperativ.

AimsDue to the known malignant potential and the poor overall prognosis of pancreatic ductal adenocarcinoma (PDAC), the identification of new biomarkers is of utmost importance. It has been reported that integrin alpha 2 (ITGA2), plakophilin 3 (PKP3) and adenylate kinase 4 (AK4) are associated with poor survival and more aggressive malignant behaviour in multiple cancers; however, their role in PDAC is still unknown. Therefore, the aim of this study was to investigate the correlation of ITGA2, PKP3 and AK4 expression with PDAC tumour characteristics and patient survival.MethodsOf 105 patients undergoing oncological pancreatic resection between 2012 and 2018, tissue microarrays were prepared from formalin-fixed, paraffin-embedded PDAC tissues and immunohistochemically stained with PKP3, AK4 and ITGA2. Clinical and pathological patient data were retrieved from the electronic patient charts and correlated with biomarker staining scores.ResultsITGA2 expression was high in 43% of patients with PDAC, whereas AK4 and PKP3 expressions were high in 28% and 57%, respectively. Overall survival was negatively associated with high ITGA2 expression in comparison with low expression (13 months (95% CI 10 to 18 months) vs 25 months (95% CI 20 to 30 months), pConclusionsITGA2 is an independent prognostic parameter for survival in patients with resected PDAC. PKP3 and AK4 do not appear to have prognostic value for survival in PDAC.

Realistic preclinical models of primary pancreatic cancer and metastasis are urgently needed to test the therapy response ex vivo and facilitate personalized patient treatment. However, the absence of tumor-specific microenvironment in currently used models, e.g., patient-derived cell lines and xenografts, only allows limited predictive insights. Organotypic slice cultures (OTSCs) comprise intact multicellular tissue, which can be rapidly used for the spatially resolved drug response testing. This protocol describes the generation and cultivation of viable tumor slices of pancreatic cancer and its metastasis. Briefly, tissue is casted in low melt agarose and stored in cold isotonic buffer. Next, tissue slices of 300 µm thickness are generated with a vibratome. After preparation, slices are cultured at an air-liquid interface using cell culture inserts and an appropriate cultivation medium. During cultivation, changes in cell differentiation and viability can be monitored. Additionally, this technique enables the application of treatment to viable human tumor tissue ex vivo and subsequent downstream analyses, such as transcriptome and proteome profiling. OTSCs provide a unique opportunity to test the individual treatment response ex vivo and identify individual transcriptomic and proteomic profiles associated with the respective response of distinct slices of a tumor. OTSCs can be further explored to identify therapeutic strategies to personalize treatment of primary pancreatic cancer and metastasis.

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.

In view of the limited capacities in intensive care units and the increasing economic burden, identification of risk factors could allow better and more efficient planning. Therefore, the aim of this study was to assess independent risk factors for the duration of intensive care unit stay after pancreatoduodenectomy (PD).147 patients who underwent pancreatoduodenectomy in the time period from 2013 to 2015 were identified from a prospective database and a retrospective analysis was performed. The primary endpoint was length of time spent in the ICU. A retrograde analysis was performed using univariate and multivariate regression analysis. All pre-, intra- and postoperative parameters were considered in the analysis.The median time spent in the intensive care unit (ICU) is one day. The univariate analysis demonstrated increased pack years, cerebrovascular events, anticoagulation, elevated creatinine and CA 19-9 as preoperative risk factors. In multivariate analysis, antihypertensive medication (AHT; OR 2.46; 95% CI 1.57 - 3.87; p = 0.05), operation time (OR 1.01; 95% CI 1.00 - 1.01; p = 0.03), extended LAD (OR 5.46; 95% CI 2.77 - 10.75; p = 0.01) and severe PPH (OR 4.01; 95% CI 2.07 - 7.76; p = 0.04) are significant risk factors for longer ICU stay.Patients with cardiovascular risk factors and elevated preoperative creatinine level are at greater risk for a prolonged ICU stay. Risk and benefit of an extended LAD should be weighed during the operation. Median duration on ICU/IMC after PD is one day or less for patients without risk factors. Whether routine monitoring in the ICU/IMC after PD is necessary must be clarified in further studies.Angesichts der begrenzten intensivmedizinischen Kapazitäten und der zunehmenden wirtschaftlichen Belastung könnte die Ermittlung von Risikofaktoren für intensivmedizinische Nachbetreuung eine bessere und effizientere Planung ermöglichen. Ziel dieser Studie war es daher, unabhängige Risikofaktoren für die Dauer des Aufenthaltes auf der Intensivstation nach der Pankreatoduodenektomie (PD) zu ermitteln.147 Patienten, die sich im Zeitraum 2013 – 2015 einer PD unterzogen hatten, wurden aus einer prospektiven Datenbank identifiziert und eine retrospektive Analyse wurde durchgeführt. Der primäre Endpunkt war die Dauer der Zeit, die auf der Intensivstation verbracht wurde. Eine uni- und multivariate Regressionsanalyse wurden durchgeführt, um prä-, intra- und postoperative Risikofaktoren zu ermitteln. Alle erhobenen prä-, intra- und postoperativen Parameter wurden in der Analyse berücksichtigt.Die durchschnittliche Liegezeit auf der Intensivstation nach PD beträgt 1 Tag. Die univariate Analyse zeigte bei den präoperativen Risikofaktoren vermehrte Pack Years, zerebrovaskuläre Ereignisse, Antikoagulation, erhöhtes Kreatinin und CA 19-9 als präoperative Risikofaktoren. In der multivariaten Analyse waren antihypertensive Medikamente (OR 2,46; 95%-KI 1,57 – 3,87; p = 0,05), Operationszeit (OR 1,01; 95%-KI 1,00 – 1,01; p = 0,03), erweiterte Lymphadenektomie (OR 5,46; 95%-KI 2,77 – 10,75; p = 0,01) und die schwere pankreasspezifische Nachblutung (PPH Grad B/C; OR 4,01; 95%-KI 2,07 – 7,76; p = 0,04) signifikante Risikofaktoren für einen verlängerten Intensivaufenthalt.Patienten mit kardiovaskulären Risikofaktoren und erhöhten präoperativen Kreatininwerten haben ein höheres Risiko für einen längeren Aufenthalt auf der Intensivstation. Risiko und Nutzen einer erweiterten Lymphadenektomie sollten während der Operation abgewogen werden. Patienten ohne Risikofaktoren liegen im Median ≤ 1 Tag auf der ITS/IMC. Ob daher eine routinemäßige Überwachung auf der ITS/IMC nach PD nötig ist, muss in weiteren Studien geklärt werden.

Introduction: Ampullary adenocarcinoma (AAC) is a rare malignancy with great morphological heterogeneity, which complicates the prediction of survival and, therefore, clinical decision-making. The aim of this study was to develop and externally validate a prediction model for survival after resection of AAC. Materials and methods: An international multicenter cohort study was conducted, including patients who underwent pancreatoduodenectomy for AAC (2006–2017) from 27 centers in 10 countries spanning three continents. A derivation and validation cohort were separately collected. Predictors were selected from the derivation cohort using a LASSO Cox proportional hazards model. A nomogram was created based on shrunk coefficients. Model performance was assessed in the derivation cohort and subsequently in the validation cohort, by calibration plots and Uno's C-statistic. Four risk groups were created based on quartiles of the nomogram score. Results: Overall, 1007 patients were available for development of the model. Predictors in the final Cox model included age, resection margin, tumor differentiation, pathological T stage and N stage (8th AJCC edition). Internal cross-validation demonstrated a C-statistic of 0.75 (95% CI 0.73–0.77). External validation in a cohort of 462 patients demonstrated a C-statistic of 0.77 (95% CI 0.73–0.81). A nomogram for the prediction of 3- and 5-year survival was created. The four risk groups showed significantly different 5-year survival rates (81%, 57%, 22% and 14%, p < 0.001). Only in the very-high risk group was adjuvant chemotherapy associated with an improved overall survival. Conclusion: A prediction model for survival after curative resection of AAC was developed and externally validated. The model is easily available online via www.pancreascalculator.com.

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.

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. (3) 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&ndash, 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.

Background: The objective of this study was to validate and update the Amsterdam prediction model including tumor grade, lymph node ratio, margin status and adjuvant therapy, for prediction of overall survival (OS) after pancreatoduodenectomy for pancreatic cancer.Methods: We included consecutive patients who underwent pancreatoduodenectomy for pancreatic cancer between 2000 and 2017 at 11 tertiary centers in 8 countries (USA, UK, Germany, Italy, Sweden, the Netherlands, Korea, Australia). Model performance for prediction of OS was evaluated by calibration statistics and Uno's C-statistic for discrimination. Validation followed the TRIPOD statement.Results: Overall, 3081 patients (53% male, median age 66 years) were included with a median OS of 24 months, of whom 38% had N2 disease and 77% received adjuvant chemotherapy. Predictions of 3-year OS were fairly similar to observed OS with a calibration slope of 0.72. Statistical updating of the model resulted in an increase of the C-statistic from 0.63 to 0.65 (95% CI 0.64-0.65), ranging from 0.62 to 0.67 across different countries. The area under the curve for the prediction of 3 -year OS was 0.71 after updating. Median OS was 36, 25 and 15 months for the low, intermediate and high risk group, respectively (P < 0.001).Conclusions: This large international study validated and updated the Amsterdam model for survival prediction after pancreatoduodenectomy for pancreatic cancer. The model incorporates readily available variables with a fairly accurate model performance and robustness across different countries, while novel markers may be added in the future. The risk groups and web-based calculator www pancreascalculaior. corn may facilitate use in daily practice and future trials. (C) 2019 Elsevier Ltd, BASO The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

The inhibition of Hedgehog (Hh) signaling in pancreatic ductal adenocarcinoma (PDAC) reduces desmoplasia and promotes increased vascularity. In contrast to these findings, the Hh ligand Sonic Hedgehog (SHH) is a potent proangiogenic factor in non-tumor models. The aim of this study was to determine the molecular mechanisms by which SHH affects the tumor stroma and angiogenesis. Mice bearing three different xenografted human PDAC (n = 5/group) were treated with neutralizing antibodies to SHH. After treatment for 7 days, tumors were evaluated and the expression of 38 pro- and antiangiogenic factors was assessed in the tumor cells and their stroma. The effect of SHH on the regulation of pro- and antiangiogenic factors in fibroblasts and its impact on endothelial cells was then further assessed in in vitro model systems. Inhibition of SHH affected tumor growth, stromal content, and vascularity. Its effect on the Hh signaling pathway was restricted to the stromal compartment of the three cancers. SHH-stimulated angiogenesis indirectly through the reduction of antiangiogenic THBS2 and TIMP2 in stromal cells. An additional direct effect of SHH on endothelial cells depended on the presence of VEGF. Inhibition of Hh signaling reduces tumor vascularity, suggesting that Hh plays a role in the maintenance or formation of the tumor vasculature. Whether the reduction in tumor growth and viability seen in the epithelium is a direct consequence of Hh pathway inhibition, or indirectly caused by its effect on the stroma and vasculature, remains to be evaluated.

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.

Upper gastrointestinal malignancies are associated with a high disease burden worldwide, and esophageal and gastric cancers represent the most common entities. Given a lack of early characteristic symptoms and potent screening instruments, the majority of patients present with advanced disease at the time of diagnosis. Complete surgical resection is a first-line curative option, and multimodal approaches involving chemotherapy and radiotherapy further improve patient prognosis. However, response to standard adjuvant and neoadjuvant treatments remains low, and new strategies are warranted to increase tumor control rates. Immunotherapy is emerging in various cancer entities and may be successfully combined with standard therapeutic regimens to improve patient outcome. For the purpose of this review we aimed to assess combined approaches of immunotherapy and standard treatment options such as chemotherapy, radiotherapy and surgery. Current trials evaluating multimodal approaches with immunotherapy in esophageal and gastric cancer are evaluated.

Laparoscopic pancreatoduodenectomy is a highly challenging procedure. The aim of this study was to analyse post-operative morbidity and mortality as well as long term overall survival in patients undergoing hybrid LPD, as compared to open pancreaticoduodenecomy (OPD) in a single surgeon series.Patients undergoing pancreatoduodenectomy (PD) in the period from 2000 to 2015 were identified from a prospectively maintained database. All LPD procedures were performed by one specialised pancreatic surgeon (TK). Patients were matched 1 : 1 for age, sex, BMI, ASA, histological diagnosis, pancreatic texture and portal venous resection (PVR). All LPD procedures were performed as hybrid LPD - combining laparoscopic resection and open reconstruction via mini laparotomy.A total of 549 patients were identified, including 489 patients in the OPD group and 60 patients in the LPD group. 60 patients were identified who underwent LPD between 2010 and 2015 versus 60 OPD patients operated in the same period. Median overall operation time was shorter in the LPD group than with OPD patients (LPD 352 vs. OPD 397 min; p = 0.002). Overall transfusion units were lower in the LPD group (LPD range 0 - 4 vs. OPD range 0 - 11; p = 0.032). Intensive care unit stay (LPD 1 vs. OPD 6 d; p = 0.008) and overall hospital stay (OHS: LPD 14 vs. OPD 18 d; p = 0.012) were shorter in the LPD groups than in the OPD group. As regards postoperative complications, LPD was associated with reduced rates of clinically relevant grade B/C postoperative pancreatic fistula (LPD 15 vs. OPD 36%; p = 0.036) and grade B/C delayed gastric emptying (LPD 8 vs. OPD 20%; p = 0.049). A total of 56 patients were diagnosed with malignant disease. The number of harvested lymph nodes and R0-resection rates were equal for LPD and OPD patients. LPD patients showed a trend to improved median overall survival (LPD mean 56 months vs. OPD mean 48 months; p = 0.056).Hybrid LPD is a safe procedure associated with a reduction in clinically relevant postoperative complications and allows faster recovery. Long term oncological outcome of hybrid LPD for malignant disease is equal to that with the standard open approach.Ziel dieser Studie war es, die postoperative Morbidität und Mortalität sowie Langzeit-Gesamtüberlebensraten bei Patienten nach laparoskopischer Pankreatoduodenektomie (LPD) in Hybridtechnik im Vergleich zur offenen Pankreatoduodenektomie (OPD) anhand der Serie eines LPD-spezialisierten Pankreaschirurgen zu analysieren.Daten von Patienten, die im Zeitraum 2000 – 2015 eine Pankreatoduodenektomie (PD) erhalten haben, wurden einer prospektiv geführten Datenbank entnommen. Alle LPD-Resektionen wurden von einem Chirurgen (TK) durchgeführt. Es erfolgte ein 1 : 1 Matching der Patienten anhand der Parameter Alter, Geschlecht, BMI, ASA, Histologie, Textur des Pankreasparenchyms und Durchführung einer Pfortaderresektion. Alle LPD-Resektionen wurden in Hybridtechnik mit laparoskopischer Resektion und anschließender Rekonstruktion mittels Minilaparotomie durchgeführt.Insgesamt konnten 549 Patienten anhand der Datenbank identifiziert werden, 489 Patienten in der OPD-Gruppe und 60 Patienten in der LPD-Gruppe. 60 LPD-Patienten aus dem Zeitraum 2010 – 2015 und 60 OPD-Patienten aus dem Zeitraum 2000 – 2015 wurden in die Studie eingeschlossen. Die mediane Operationszeit in der LPD-Gruppe war verkürzt im Vergleich zur OPD-Gruppe (LPD 352 vs. OPD 397 min; p = 0,002). Die Anzahl perioperativ benötigter Erythrozytenkonzentrate war geringer in der LPD-Gruppe (LPD 0 – 4 vs. OPD 0 – 11; p = 0,032). Die mediane Dauer der intensivmedizinischen Therapie (LPD 1 vs. OPD 6 d; p = 0,008) und die mediane Gesamtdauer des Krankenhausaufenthalts (LPD 14 vs. OPD 18 d; p = 0,012) waren kürzer in der LPD-Gruppe im Vergleich zur offenen Resektion. Die LPD war mit einer geringeren Rate klinisch relevanter Grad-B/C-Pankreasfisteln (LPD 15 vs. OPD 36%; p = 0,036) und verzögerter Magenentleerung Grad B/C assoziiert (LPD 8 vs. OPD 20%; p = 0,049). 56 der eingeschlossenen Patienten wiesen eine maligne Raumforderung auf. Die Anzahl resezierter Lymphknoten und die Rate an R0-Resektionen waren vergleichbar in der LPD- und der OPD-Gruppe. Bei LPD-Patienten zeigte sich der Trend einer verbesserten medianen Gesamtüberlebensrate (LPD 56 vs. OPD 48 Monate; p = 0,056).Die LPD in Hybridtechnik ist eine sichere Technik, die mit der Reduktion klinisch relevanter postoperativer Komplikationen assoziiert ist und eine schnelle postoperative Erholung erlaubt. Die onkologischen Langzeitergebnisse nach LPD in Hybridtechnik bei malignen Befunden sind gleichwertig zur offenen Technik.