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CCR Translation for This Article from Plectin-1 as a Novel Biomarker for Pancreatic Cancer

Purpose: We are in great need of specific biomarkers to detect pancreatic ductal adenocarcinoma (PDAC) at an early stage, ideally before invasion. Plectin-1 (Plec1) was recently identified as one such biomarker. However, its suitability as a specific biomarker for human pancreatic cancer, and its usability as an imaging target, remain to be assessed.Experimental Design: Specimens of human PDAC, chronic pancreatitis, and normal pancreata were evaluated by immunohistochemistry and Western blot analysis. To validate Plec1 as an imaging target, Plec1-targeting peptides (tPTP) were used as a contrast agent for single photon emission computed tomography in an orthotopic and liver metastasis murine model of PDAC.Results: Plec1 expression was noted to be positive in all PDACs but negative in benign tissues. Plec1 expression increases during pancreatic carcinogenesis. It was found to be misexpressed in only 0% to 3.85% of early PDAC precursor lesions (PanIN I/II) but in 60% of PanIN III lesions. Plec1 expression was further noted to be retained in all metastatic foci assayed and clearly highlighted these metastatic deposits in lymph nodes, liver, and peritoneum. In vivo imaging using tPTP specifically highlighted the primary and metastatic tumors. Biodistribution studies performed after imaging show that the primary pancreatic tumors and liver metastases retained 1.9- to 2.9-fold of tPTP over normal pancreas and 1.7-fold over normal liver.Conclusions: Plec1 is the first biomarker to identify primary and metastatic PDAC by imaging and may also detect preinvasive PanIN III lesions. Strategies designed to image Plec1 could therefore improve detection and staging. Clin Cancer Res; 17(2); 302–9. ©2010 AACR.

ZusammenfassungMinimalinvasive Resektionstechniken zur Behandlung verschiedener Pathologien des Pankreas sind potenziell vorteilhaft für die behandelten Patienten in Bezug auf Rekonvaleszenzzeit und postoperative Morbidität, stellen jedoch eine besondere technische Herausforderung für den behandelnden Chirurgen dar. Der Einzug der robotischen Technik in die Viszeralchirurgie bietet eine prinzipielle Möglichkeit zur weitreichenden Verbreitung minimalinvasiver Verfahren in der Pankreaschirurgie.Ziel dieser Arbeit war es, die Entwicklungsmöglichkeiten der robotischen Pankreaschirurgie in Deutschland zu überprüfen. Datengrundlage sind die Qualitätsberichte der Krankenhäuser der Jahre 2015–2019 kombiniert mit einer selektiven Literaturrecherche.Die Anzahl der vorliegenden Qualitätsberichte reduzierte sich von 2015 bis 2019 von 1635 auf 1594. Im Median führten 96 Kliniken 11–20, 56 Kliniken 21–50 und 15 Kliniken mehr als 50 Pankreaskopfresektionen jährlich durch. Bei den Linksresektionen waren es 35 Kliniken mit 11–20, 14 Kliniken mit 21–50 und 2 Kliniken mit mehr als 50 Eingriffen. Unter Berücksichtigung aller Kliniken, die 5 oder mehr Linksresektionen pro Jahr durchführen, wurden an nur 29 Kliniken minimalinvasive Verfahren eingesetzt. Der Anteil an laparoskopischen Linksresektionen über 50% wurde an nur 7 Kliniken beschrieben.Nach Datenlage in der Literatur divergieren die Lernkurven für die robotische Pankreaslinks- und Pankreaskopfresektion. Während die Lernkurve für die robotische Pankreaslinksresektion nach etwa 20 Eingriffen durchlaufen ist, hat die Lernkurve für die robotische Pankreaskopfresektion mehrere Plateaus, die etwa nach 30, 100 und 250 Eingriffen erreicht werden.Aufgrund der dezentralen Struktur der Pankreaschirurgie in Deutschland scheint ein flächendeckendes Angebot robotischer Verfahren aktuell in weiter Ferne. Insbesondere die Etablierung der robotischen Pankreaskopfresektion wird zunächst Zentren mit entsprechend hoher Fallzahl vorbehalten bleiben.

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.

ZusammenfassungDas Pankreaskarzinom im Bereich des Korpus und linksseitig der mesenterikoportalen Achse wird wegen der unspezifischen oder gar fehlenden klinischen Symptome häufig erst in späten Stadien erkannt, wobei in etwa 20% der Fälle bereits eine Infiltration der umliegenden arteriellen oder venösen Gefäße vorliegt. Trotz eines lokal fortgeschrittenen Wachstums (T4, UICC-Stadium III) weisen 30% der Patienten keine Fernmetastasen auf und würden sich potenziell für eine lokale Resektion qualifizieren. Arterielle Resektionen mit Anastomosierung und Gefäßrekonstruktion sind einschränkend mit einer fast 9-fach erhöhten Mortalität des Eingriffs im Vergleich zu Resektionen ohne Gefäßrekonstruktion verbunden. Die Appleby-Operation stellt eine komplexe Operationstechnik dar, die ursprünglich für das fortgeschrittene Magenkarzinom entwickelt wurde. Die Adaptation der Technik wurde für Patienten mit fortgeschrittenen Pankreaskorpus- und Pankreasschwanztumoren mit einer Infiltration des Truncus coeliacus weiterentwickelt. Der Vorteil der Operation besteht darin, dass technisch keine Rekonstruktion der resezierten Arterien erfolgen muss, da man sich eine natürliche interne Anastomose im Pankreaskopf zwischen der A. mesenterica superior und der A. hepatica über Äste der A. gastroduodenalis zum Erhalt der Leberperfusion und der Magendurchblutung zu Nutze macht. Das Operationsverfahren ist jedoch ebenso mit einer hohen Morbidität und Mortalität verbunden mit vergleichbar schlechten onkologischen Ergebnissen (R0-Raten ca. 60%), sodass das Verfahren bis vor einigen Jahren nicht empfohlen wurde und die Patienten als inoperabel galten. Im Zuge der Entwicklung neoadjuvanter Therapieverfahren beim Pankreaskarzinom wird die Appleby-Operation wieder häufiger durchgeführt, da der Bedarf an lokal radikal resezierenden Operationsverfahren und Techniken im Kontext der multimodalen Behandlung gestiegen ist. Im Zuge der derzeitigen Etablierung der Robotik in der Viszeralchirurgie könnten bisherige Limitationen der minimalinvasiven Pankreaschirurgie überwunden werden und deutlich mehr Patienten die Vorteile der minimalinvasiven Chirurgie – wie eine schnellere Rekonvaleszenz – ermöglicht werden. Der Einsatz robotischer Operationsverfahren ermöglicht die Erweiterung minimalinvasiver Techniken in den Bereich der komplexen Gefäßresektion und Rekonstruktion. Im vorliegenden Videobeitrag beschreiben wir eine robotisch assistierte modifizierte Appleby-Operation mit dem Einsatz des Da Vinci Xi Surgical System bei einer Patientin mit einem fortgeschrittenen Pankreaskorpuskarzinom nach neoadjuvanter Therapie.

Minimally invasive resection techniques for the treatment of various pathologies of the pancreas are potentially advantageous for the treated patients in terms of restitution time and postoperative morbidity, but are a technical challenge for the responsible surgeon. The introduction of robotic assistance in visceral surgery offers a possibility for further distribution of minimally invasive procedures in pancreatic surgery.The aim of this study was to examine the possibilities for developing robotic pancreatic surgery in Germany. The data are based on the quality reports of the hospitals for the years 2015-2019 combined with a selective literature search.The number of quality reports available decreased from 1635 to 1594 between 2015 and 2019. A median of 96 clinics performed 11-20, 56 clinics 21-50 and 15 clinics more than 50 pancreaticoduodenectomies. For distal resections, there were 35 clinics with 11-20, 14 clinics with 21-50 and two clinics with more than 50 procedures. In relation to all clinics with at least five distal resections per year, minimally invasive procedures were performed at only 29 clinics; a ratio to laparoscopic left resections of over 50% was reported in only seven clinics.According to the literature, the learning curves for robotic pancreatic distal resection and pancreaticoduodenectomy diverge. While the learning curve for robotic distal resection is completed after around 20 procedures, the learning curve for robotic pancreaticoduodenectomy has several plateaus, which are reached after around 30, 100 and 250 procedures.Due to the decentralised structure of pancreatic surgery in Germany, a nationwide introduction of robotic pancreatic surgery is unlikely. The routine use of robotic pancreaticoduodenectomy will probably be restricted to high volume centres in the foreseeable future.Minimalinvasive Resektionstechniken zur Behandlung verschiedener Pathologien des Pankreas sind potenziell vorteilhaft für die behandelten Patienten in Bezug auf Rekonvaleszenzzeit und postoperative Morbidität, stellen jedoch eine besondere technische Herausforderung für den behandelnden Chirurgen dar. Der Einzug der robotischen Technik in die Viszeralchirurgie bietet eine prinzipielle Möglichkeit zur weitreichenden Verbreitung minimalinvasiver Verfahren in der Pankreaschirurgie.Ziel dieser Arbeit war es, die Entwicklungsmöglichkeiten der robotischen Pankreaschirurgie in Deutschland zu überprüfen. Datengrundlage sind die Qualitätsberichte der Krankenhäuser der Jahre 2015–2019 kombiniert mit einer selektiven Literaturrecherche.Die Anzahl der vorliegenden Qualitätsberichte reduzierte sich von 2015 bis 2019 von 1635 auf 1594. Im Median führten 96 Kliniken 11–20, 56 Kliniken 21–50 und 15 Kliniken mehr als 50 Pankreaskopfresektionen jährlich durch. Bei den Linksresektionen waren es 35 Kliniken mit 11–20, 14 Kliniken mit 21–50 und 2 Kliniken mit mehr als 50 Eingriffen. Unter Berücksichtigung aller Kliniken, die 5 oder mehr Linksresektionen pro Jahr durchführen, wurden an nur 29 Kliniken minimalinvasive Verfahren eingesetzt. Der Anteil an laparoskopischen Linksresektionen über 50% wurde an nur 7 Kliniken beschrieben.Nach Datenlage in der Literatur divergieren die Lernkurven für die robotische Pankreaslinks- und Pankreaskopfresektion. Während die Lernkurve für die robotische Pankreaslinksresektion nach etwa 20 Eingriffen durchlaufen ist, hat die Lernkurve für die robotische Pankreaskopfresektion mehrere Plateaus, die etwa nach 30, 100 und 250 Eingriffen erreicht werden.Aufgrund der dezentralen Struktur der Pankreaschirurgie in Deutschland scheint ein flächendeckendes Angebot robotischer Verfahren aktuell in weiter Ferne. Insbesondere die Etablierung der robotischen Pankreaskopfresektion wird zunächst Zentren mit entsprechend hoher Fallzahl vorbehalten bleiben.

Zusammenfassung Einleitung Die robotisch assistierte Chirurgie ist eine vielversprechende Technik zur Überwindung der Grenzen der laparoskopischen Chirurgie – insbesondere bei komplexen chirurgischen Eingriffen in der Oberbauchchirurgie. Im Folgenden beschreiben wir die Etablierung komplexer robotisch assistierter Oberbauchchirurgie in unserem Zentrum für minimalinvasive Chirurgie und präsentieren die Ergebnisse aus den ersten 100 Eingriffen. Material und Methoden Die robotisch assistierte Chirurgie wurde mit dem Da Vinci® Xi Surgical System™ durchgeführt. Die Eingriffe wurden von 2 Chirurgen durchgeführt, die Spezialisten auf dem Gebiet der minimalinvasiven Chirurgie sind. Die robotisch assistierte Oberbauchchirurgie wurde in 3 Schritten etabliert. Step 1: Zunächst wurden robotisch assistierte Eingriffe mit leichterem Schwierigkeitsgrad durchgeführt (Cholezystektomien, atypische Magenresektionen und Fundoplikationen). Step 2: Anschließend wurden linksseitige Pankreasresektionen, Adrenalektomien und Lebersegment- bzw. atypische Leberresektionen als Verfahren mit mittlerem Schwierigkeitsgrad durchgeführt. Step 3: Schließlich wurden fortgeschrittene und hochkomplexe Verfahren durchgeführt (Hemihepatektomien, komplexe Pankreasresektionen, Gastrektomien und Ösophagektomien). Die von Juli 2017 bis Oktober 2018 erhobenen Daten wurden retrospektiv hinsichtlich Konversionsrate, Morbidität (Clavien-Dindo > 2) und Mortalität analysiert. Ergebnisse Der 1. Schritt der Etablierung unseres Roboterprogramms umfasste 26 Eingriffe. Hier betrugen die Konversionsrate, die Morbidität und die Mortalität jeweils 0%. Im 2. Schritt wurden 23 Eingriffe durchgeführt. Die Konversionsrate, Morbidität und Mortalität lagen bei 28, 8 und 0%. Der letzte Schritt umfasste 51 hochkomplexe operative Verfahren. Diese Verfahren hatten eine Konversionsrate 43%, eine Morbidität von 41% und eine Mortalität von 4%. Schlussfolgerung Unser Stepwise Approach ermöglicht eine sichere Etablierung robotisch assistierter Oberbauchchirurgie mit vergleichbaren Morbiditäts- und Mortalitätsraten – auch bei hochkomplexen operativen Eingriffen. Hochkomplexe Eingriffe erforderten jedoch vergleichsweise häufig eine Konversion, was durch die geringen Erfahrungswerte und durch die Lernkurve beeinflusst sein könnte.

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.

Purpose Laparoscopic rectosigmoid resection rectopexy (LRR) is the most effective treatment of obstructive defecation syndrome but is associated with a higher postoperative morbidity compared to transanal approaches. Natural orifice specimen extraction (NOSE) has been described as a promising technique to lower morbidity in colorectal cancer surgery. In this study, we analyze the technical challenges of adapting this technique to LRR and compare the perioperative results to the conventional laparoscopic technique with specimen extraction via minilaparotomy and extracorporeal anastomosis. Methods We retrospectively analyzed 45 patients who underwent laparoscopic rectosigmoid resection rectopexy due to obstructive defecation syndrome at our institutions. From September 2020 to July 2021, we treated 17 consecutive patients with NOSE-LRR and compared the results to a historic cohort of 28 consecutive patients treated with conventional laparoscopic rectosigmoid resection rectopexy plus minilaparotomy (LAP-LRR) for specimen extraction between January 2019 and July 2020. Assessed were patient- and disease-specific parameters, operative time, hospital and postoperative complications and subjective patient satisfaction after 6 months of follow-up. Results Both groups were comparable in terms of gender distribution, age, and comorbidities. The median operating time was similar and the perioperative morbidity was comparable in both groups. The length of stay in hospital was significantly shorter in the NOSE-LRR group (median 6 vs 8 days). Conclusion NOSE-LRR can be implemented safely, performed in a comparable operating time, and is associated with a comparable rate of postoperative complications. The technique offers the a potentially fast postoperative recovery compared to the conventional laparoscopic technique.

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.

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.

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.

ZusammenfassungDie postoperative Delayed Graft Function (DGF) nach Nierentransplantationen ist definiert als eine Einschränkung der Nierenfunktion nach Nierentransplantation und ist Risikofaktor für ein Transplantatversagen und verkürztes Transplantatüberleben. Ziel dieser Studie war es, die quantitative Perfusion von Nierentransplantaten während der Nierentransplantation zu erfassen und zu untersuchen, ob die gemessene Perfusion Rückschlüsse auf das postoperative Auftreten einer DGF erlaubt. In einem Zeitraum von 1 Jahr wurde bei den Patienten, bei denen ein Einverständnis für die ICG-Perfusionsmessung vorlag, die intraoperative quantitative ICG-Perfusionsmessung mithilfe der Kamera IC-View der Firma Pulsion® durchgeführt. Es erfolgte die Gruppeneinteilung nach postmortaler Spende und Lebendspenden und nach Auftreten bzw. Ausbleiben einer DGF. Intraoperativ erfolgte die Festlegung eines Areals mit starker und geringer ICG-Perfusion. Es wurden die maximale Perfusion, die Anflutzeit der Fluoreszenz und der absolute Anstieg der Fluoreszenz in diesen Arealen dokumentiert. Zusätzlich erfolgte die Berechnung der maximalen Perfusion im Verhältnis zu einem Standardareal. Postoperativ erfolgte die Auswertung durch die Software IC-Calc der Firma Pulsion. Insgesamt konnten 36 Patienten in die Studie eingeschlossen werden. Komplikationen durch die ICG-Applikation traten nicht auf. Bei 10 Patienten, die eine postmortale Nierentransplantatspende erhielten, wurde eine DGF festgestellt (DGF-Gruppe). In der Gruppe der Lebendspende trat eine DGF nicht auf. In den Arealen mit starker ICG-Fluoreszenz fand sich ein signifikanter Unterschied in der maximalen Fluoreszenz zwischen der DGF-Gruppe und Nierenlebendspenden. Die schwach perfundierten Areale wiesen signifikante Unterschiede zwischen der maximalen Perfusion, dem absoluten Anstieg der Perfusion sowie zur Ratio zum Standardareal zwischen DGF und Lebendspenden auf. Ein Unterschied zwischen postmortalen Nierentransplantatspenden ohne DGF und DGF-Gruppe konnte nicht nachgewiesen werden. In dieser Studie zeigte sich, dass sich die quantitative Perfusionsbestimmung von Nierentransplantaten intraoperativ sicher durchführen lässt. Die aktuelle Datenlage deutet eine mögliche zuverlässige Vorhersage der DGF an.

Minimally invasive donor nephrectomy has become the standard procedure in most transplant centres over the past two decades and has contributed to a reduction in postoperative morbidity for the donor. Robot-assisted technology is an alternative to conventional (hand-assisted) laparoscopic technology and will find increasing use in the future. In this review article, we address technical aspects of robotic-assisted donor nephrectomy, in accordance with our own experience and will provide an overview of the currently available literature. Robot-assisted living kidney donation is a safe procedure with a very low postoperative complication rate. The procedure offers advantages over the open surgical technique with respect to the reduction in the postoperative need for analgesia and the duration of hospital stay, with longer operating times and warm ischemia times, but without a measurable effect on transplant function. The postoperative outcome parameters are comparable to those of the laparoscopic technique, indicating a further acceleration of postoperative convalescence. The advantages of robot-assisted technology, due to the better exposure options, are most relevant in patients with a high BMI and multiple renal arteries, as well as in right-sided nephrectomies in which a longer transplant artery can be obtained. Robot-assisted living kidney donation will play a major role in the future of transplant surgery and is a serious alternative to conventional laparoscopic technology.Die minimalinvasive Nephrektomie zur Lebendspende hat sich über die letzten 2 Jahrzehnte zum Standard in den meisten Transplantationszentren entwickelt und hat zu einer Reduktion der postoperativen Morbidität beim Spender beigetragen. Die robotisch assistierte Technik stellt eine Alternative zur herkömmlichen (handassistierten) laparoskopischen Technik dar und wird in der Zukunft vermehrt Anwendung finden. In dieser Übersichtsarbeit gehen wir anhand unserer eigenen Erfahrungen auf technische Aspekte der robotischen Nephrektomie ein und geben einen Überblick über die aktuell verfügbare Literatur. Die robotisch assistierte Nierenlebendspende ist ein sicherer Eingriff mit einer sehr geringen postoperativen Komplikationsrate. Ein Vorteil des Eingriffs gegenüber der offenen Operationstechnik liegt in einer Reduktion des postoperativen Analgetikabedarfs und einer vergleichsweise reduzierten Krankenhausverweildauer bei jedoch verlängerter Operations- und Warmischämiezeit ohne messbaren Effekt auf die Transplantatfunktion. Die Ergebnisse entsprechen im Wesentlichen denen der laparoskopischen Technik, wobei sich eine weitere Beschleunigung der postoperativen Rekonvaleszenz andeutet. Die Vorteile der robotisch assistierten Technik liegen aufgrund der besseren Expositionsmöglichkeiten vornehmlich bei Patienten mit hohem BMI und multiplen Nierenarterien sowie bei rechtsseitigen Nephrektomien, bei denen eine längere Transplantatarterie gewonnen werden kann. Die robotisch assistierte Nierenlebendspende ist aus der Zukunft der Transplantationschirurgie nicht mehr wegzudenken und stellt eine ernst zu nehmende Alternative zur herkömmlichen laparoskopischen Technik dar.

Pancreatic carcinoma in the body and on the left side of the mesentericoportal axis is often only detected in late stages owing to unspecific or even missing clinical symptoms. In approximately 20% of the cases, there is already infiltration of the tumour into the surrounding arteries or veins. Despite locally advanced growth, 30% of patients do not have distant metastases and would potentially qualify for local resection. Arterial resections and vascular reconstruction are associated with an almost 9-fold increase in postoperative mortality compared with resections without vascular reconstruction. The Appleby procedure is a complex surgical technique originally developed for advanced gastric cancer. The technique has been further developed for patients with advanced pancreatic body and tail tumours with infiltration of the coeliac trunk (modified Appleby procedure). The advantage of the procedure is that technically, no reconstruction of the resected arteries is required. This is because a natural internal anastomosis in the pancreatic head between the A. mesenterica superior and the A. hepatica via branches of the A. gastroduodenalis is used to maintain liver perfusion and gastric blood flow. However, the surgical procedure is also associated with high morbidity and mortality, with comparably poor oncological results (R0 rates of approximately 60%). Therefore, the procedure was not recommended until a few years ago, and patients were considered inoperable. With developments in neoadjuvant therapy for pancreatic carcinoma, the Appleby procedure is being performed more frequently, with the goal of improving oncological outcomes in the context of multimodal treatment. With developments in robotics in visceral surgery, the previous limitations of minimally invasive pancreatic surgery can be overcome, and significantly more patients may benefit from the advantages of this minimally invasive surgery, such as faster convalescence. The use of robotic surgical techniques allows the extension of minimally invasive techniques into the field of complex vessel resection and reconstruction. In this video contribution, we describe a robot-assisted modified Appleby procedure using the Da Vinci Xi Surgical System in a patient with advanced pancreatic carcinoma of the pancreatic body, after neoadjuvant therapy.Das Pankreaskarzinom im Bereich des Korpus und linksseitig der mesenterikoportalen Achse wird wegen der unspezifischen oder gar fehlenden klinischen Symptome häufig erst in späten Stadien erkannt, wobei in etwa 20% der Fälle bereits eine Infiltration der umliegenden arteriellen oder venösen Gefäße vorliegt. Trotz eines lokal fortgeschrittenen Wachstums (T4, UICC-Stadium III) weisen 30% der Patienten keine Fernmetastasen auf und würden sich potenziell für eine lokale Resektion qualifizieren. Arterielle Resektionen mit Anastomosierung und Gefäßrekonstruktion sind einschränkend mit einer fast 9-fach erhöhten Mortalität des Eingriffs im Vergleich zu Resektionen ohne Gefäßrekonstruktion verbunden. Die Appleby-Operation stellt eine komplexe Operationstechnik dar, die ursprünglich für das fortgeschrittene Magenkarzinom entwickelt wurde. Die Adaptation der Technik wurde für Patienten mit fortgeschrittenen Pankreaskorpus- und Pankreasschwanztumoren mit einer Infiltration des Truncus coeliacus weiterentwickelt. Der Vorteil der Operation besteht darin, dass technisch keine Rekonstruktion der resezierten Arterien erfolgen muss, da man sich eine natürliche interne Anastomose im Pankreaskopf zwischen der A. mesenterica superior und der A. hepatica über Äste der A. gastroduodenalis zum Erhalt der Leberperfusion und der Magendurchblutung zu Nutze macht. Das Operationsverfahren ist jedoch ebenso mit einer hohen Morbidität und Mortalität verbunden mit vergleichbar schlechten onkologischen Ergebnissen (R0-Raten ca. 60%), sodass das Verfahren bis vor einigen Jahren nicht empfohlen wurde und die Patienten als inoperabel galten. Im Zuge der Entwicklung neoadjuvanter Therapieverfahren beim Pankreaskarzinom wird die Appleby-Operation wieder häufiger durchgeführt, da der Bedarf an lokal radikal resezierenden Operationsverfahren und Techniken im Kontext der multimodalen Behandlung gestiegen ist. Im Zuge der derzeitigen Etablierung der Robotik in der Viszeralchirurgie könnten bisherige Limitationen der minimalinvasiven Pankreaschirurgie überwunden werden und deutlich mehr Patienten die Vorteile der minimalinvasiven Chirurgie – wie eine schnellere Rekonvaleszenz – ermöglicht werden. Der Einsatz robotischer Operationsverfahren ermöglicht die Erweiterung minimalinvasiver Techniken in den Bereich der komplexen Gefäßresektion und Rekonstruktion. Im vorliegenden Videobeitrag beschreiben wir eine robotisch assistierte modifizierte Appleby-Operation mit dem Einsatz des Da Vinci Xi Surgical System bei einer Patientin mit einem fortgeschrittenen Pankreaskorpuskarzinom nach neoadjuvanter Therapie.

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.

Robot-assisted surgery is a promising technique for overcoming the limitations of laparoscopic surgery, especially for complex and advanced surgical procedures. We now describe the implementation of our robotic upper GI and HPB surgery program in our centre of excellence for minimally invasive surgery and the results of our first 100 surgical procedures.Robot-assisted surgery was performed using the Da VinciThe first step of establishing our robotic surgical program included 26 procedures. Here, conversion rate, morbidity and mortality were 0%. In the second step of implementation, 23 procedures were performed. Conversion rate, morbidity and mortality were 28, 8 and 0% respectively. The last step included 51 advanced and highly complex procedures. These procedures had a morbidity of 41%, a mortality of 4% and a conversion rate of 43%.Our stepwise approach enables safe implementation of a robotic surgical program for upper GI and HPB surgery with comparable morbidity and mortality even for highly complex procedures. However, highly complex procedures in the learning curve required a high conversion rate.Die robotisch assistierte Chirurgie ist eine vielversprechende Technik zur Überwindung der Grenzen der laparoskopischen Chirurgie – insbesondere bei komplexen chirurgischen Eingriffen in der Oberbauchchirurgie. Im Folgenden beschreiben wir die Etablierung komplexer robotisch assistierter Oberbauchchirurgie in unserem Zentrum für minimalinvasive Chirurgie und präsentieren die Ergebnisse aus den ersten 100 Eingriffen.Die robotisch assistierte Chirurgie wurde mit dem Da VinciDer 1. Schritt der Etablierung unseres Roboterprogramms umfasste 26 Eingriffe. Hier betrugen die Konversionsrate, die Morbidität und die Mortalität jeweils 0%. Im 2. Schritt wurden 23 Eingriffe durchgeführt. Die Konversionsrate, Morbidität und Mortalität lagen bei 28, 8 und 0%. Der letzte Schritt umfasste 51 hochkomplexe operative Verfahren. Diese Verfahren hatten eine Konversionsrate 43%, eine Morbidität von 41% und eine Mortalität von 4%.Unser Stepwise Approach ermöglicht eine sichere Etablierung robotisch assistierter Oberbauchchirurgie mit vergleichbaren Morbiditäts- und Mortalitätsraten – auch bei hochkomplexen operativen Eingriffen. Hochkomplexe Eingriffe erforderten jedoch vergleichsweise häufig eine Konversion, was durch die geringen Erfahrungswerte und durch die Lernkurve beeinflusst sein könnte.

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.

Introduction: The use of robots in minimal invasive surgery has become increasingly common in recent years.Robot-assisted pancreatoduodenectomy preponderates against a laparoscopic procedure especially due to the greater flexibility of instruments and therefore a better handling and a better angulation. Furthermore, there are benefits of enlarged 3-D visibility, software-based tremor control, and reduced physical exertion of the surgeon. Methods and Results: This review delivers a point-by-point approach to the setup of a robot-assisted pancreatic program and a detailed approach to robot-assisted pancreatoduodenectomy. Results: In our standardized standard operating procedure approach we use 5 trocars, i.e., 4 robotic trocars and 1 assist trocar. We prefer the position of the robot ports in a straight horizontal line with a distance of 20 cm from the operational field. The operation is dissected into 11 standardized procedural steps as follows: (1) access to the pancreas and visualization, (2) extended Kocher manoeuvre, (3) lower rim and mesentericoportal axis, (4) upper rim and hepatoduodenal ligament, (5) dissection of the pancreatic neck, (6) mesenteric root and pars IV duodeni, (7) mesopancreas, (8) pancreatic anastomosis reconstruction, (9) bilioenteric anastomosis, (10) dudenojejunal anastomosis, and (11) drainage and closure. The setup of the pancreas program and the structured approach to complex pancreatic resections are elucidated. Summary: This review describes the approach to robot-assisted pancreatic surgery in a high-volume pancreas center on a structural and procedural level to support the establishment of such programs at other locations.

Pancreatic neuroendocrine tumors (PanNETs) are rare in von Hippel–Lindau disease (VHL) but cause serious morbidity and mortality. Management guidelines for VHL-PanNETs continue to be based on limited evidence, and survival data to guide surgical management are lacking. We established the European-American-Asian-VHL-PanNET-Registry to assess data for risks for metastases, survival and long-term outcomes to provide best management recommendations. Of 2330 VHL patients, 273 had a total of 484 PanNETs. Median age at diagnosis of PanNET was 35 years (range 10–75). Fifty-five (20%) patients had metastatic PanNETs. Metastatic PanNETs were significantly larger (median size 5 vs 2 cm; P P = 0.001). All metastatic tumors were ≥2.8 cm. Codons 161 and 167 were hotspots for VHL germline mutations with enhanced risk for metastatic PanNETs. Multivariate prediction modeling disclosed maximum tumor diameter and TVDT as significant predictors for metastatic disease (positive and negative predictive values of 51% and 100% for diameter cut-off ≥2.8 cm, 44% and 91% for TVDT cut-off of ≤24 months). In 117 of 273 patients, PanNETs >1.5 cm in diameter were operated. Ten-year survival was significantly longer in operated vs non-operated patients, in particular for PanNETs P = 0.020; 80% vs 50% at 10 years; P = 0.030). This study demonstrates that patients with PanNET approaching the cut-off diameter of 2.8 cm should be operated. Mutations in exon 3, especially of codons 161/167 are at enhanced risk for metastatic PanNETs. Survival is significantly longer in operated non-metastatic VHL-PanNETs.

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.

AIM To compare prognostic relevance of postoperative tumour/node/metastasis (TMN) stages between patients with and without neoadjuvant treatment. METHODS Data from patients with adenocarcinoma of the gastro-oesophageal junction (AEG) who had undergone surgical resection at a single German university centre were retrospectively analysed. Patients with or without neoadjuvant preoperative treatment were selected by exact matching based on preoperative staging. Standard assessment of preoperative (c)TNM stage was based on endoscopic ultrasound and computed tomography of the thorax and abdomen, according to the American Joint Committee on Cancer/Union for International Cancer Control classification system. Patients with cT1cN0cM0 and cT2cN0cM0 stages were excluded from the study, as these patients are generally not recommended for pretreatment. Long-term survival among the various postoperative TNM stages was compared between the groups of patients with or without neoadjuvant treatment. For statistical assessments, a P-value of ≤ 0.05 was considered significant. RESULTS The study included a total of 174 patients. The group of patients who had received preoperative neoadjuvant treatment included more cases of AEG (Siewert) type 1 carcinoma (P < 0.001), and consequently oesophagectomy was performed more frequently among these patients (P < 0.001). The two groups (with or without preoperative neoadjuvant treatment) had comparable preoperative T stages, but the group of patients with preoperative neoadjuvant treatment presented a higher rate of preoperative N-positive disease (P = 0.020). Overall long-term survival was not different between the two groups of patients according to tumours of different AEG classifications, receipt of oesophagectomy or gastrectomy, nor between patients with similar postoperative TNM stage, resection margin and grading. However, an improvement of long-term survival was found for patients with nodal down-staging after neoadjuvant therapy (P = 0.053). CONCLUSION The prognostic relevance of postoperative TNM stages is similar for AEG in patients with or without neoadjuvant preoperative treatment, but treatment-related nodal down-staging prognosticates longer-term survival.

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.

Minimally invasive pancreatic procedures, in particular minimally invasive pancreaticoduodenectomy, are amongst the most technically challenging procedures in general surgery. Accordingly, a high number of cases is required to master the procedures. Minimally invasive pancreatic surgery is well established for benign and premalignant lesions of the pancreas. Borderline resectable tumors with infiltration of the portal vein are also resected minimally invasively in specialized centers with appropriate expertise. Retrospective and registry studies demonstrate an equivalent long-term survival compared to conventional surgery. Perioperative morbidity and mortality are also equivalent, whereas minimally invasive surgery significantly reduces hospital stay. We expect more widespread use of minimally invasive pancreatic procedures in large centers.

Hintergrund und Ziel der Arbeit Trotz des hohen technischen Anspruchs werden laparoskopische Operationsverfahren auch in der Pankreaschirurgie zunehmend eingesetzt. In diesem Ubersichtsartikel soll versucht werden, vor dem Hintergrund der landesweit zu hohen Mortalitat in der Pankreaschirurgie und der bisher unklaren onkologischen Validierung die Wertigkeit dieser Verfahren anhand der publizierten Literatur zu bewerten.

Postoperative delayed graft function (DGF) after kidney transplantation is a risk factor for kidney failure and reduced kidney allograft survival after transplantation. The aim of this study was to measure the quantitative perfusion of kidney transplants during kidney transplantation and to investigate whether differences in perfusion predict the development of DGF. Over a period of one year, intraoperative quantitative ICG perfusion measurements were performed with the IC-View camera (PulsionDie postoperative Delayed Graft Function (DGF) nach Nierentransplantationen ist definiert als eine Einschränkung der Nierenfunktion nach Nierentransplantation und ist Risikofaktor für ein Transplantatversagen und verkürztes Transplantatüberleben. Ziel dieser Studie war es, die quantitative Perfusion von Nierentransplantaten während der Nierentransplantation zu erfassen und zu untersuchen, ob die gemessene Perfusion Rückschlüsse auf das postoperative Auftreten einer DGF erlaubt. In einem Zeitraum von 1 Jahr wurde bei den Patienten, bei denen ein Einverständnis für die ICG-Perfusionsmessung vorlag, die intraoperative quantitative ICG-Perfusionsmessung mithilfe der Kamera IC-View der Firma Pulsion

In this retrospective study, we analyzed the association between tumor budding and perineural invasion as well as their prognostic role in pancreatic ductal adenocarcinoma. A total of N = 119 patients resected for pancreatic ductal carcinoma from 1996 to 2015 were included. Clinical and standard histopathological parameters were retrieved from the patient’s records. One representative hematoxylin and eosin section from the tumor region was examined for perineural invasion and tumor budding using light microscopy. Tumor budding was assessed independently using two different methods: in the first approach, the number of buds was counted over three fields of 0.237 mm2 at 40-fold magnification; in the second approach, tumor budding was quantified according to the recommendation of the International Tumor Budding Consensus Conference (ITBCC) over a field of 0.785 mm2 at 20-fold magnification. Linear and logistic regression was applied to delineate association between perineural invasion, tumor budding, and other parameters; Kaplan-Meier and Cox regression were used in the survival analysis. Regardless of the quantification approach, high tumor budding was a significant negative prognostic factor in the univariable Cox regression (> 5 buds/0.237 mm2, hazard ratio (HR) 1.66, 95% confidence interval (CI) 1.06–2.61, p = 0.027; ≥ 10 buds/0.785 mm2, HR 1.68, 95% CI 1.07–2.64, p = 0.024). In the multivariable model adjusting for stage and standard histopathological parameters, lymph vessel invasion (HR = 2.43, 95% CI 1.47–4.03, p = 0.001) and tumor budding > 5 buds/0.237 mm2 (HR = 1.70, 95% CI 1.07–2.7, p = 0.026) were independent negative prognostic factors, while adjuvant therapy was a positive prognostic factor (HR = 0.54, 95% CI 0.33–0.86, p = 0.009). No significant prognostic value could be delineated for perineural invasion. In conclusion, tumor budding is an independent negative prognostic factor in pancreatic ductal adenocarcinoma associated with lymph node metastasis. The prognostic role of perineural invasion remains uncertain.

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.

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

Minimally-invasive techniques were adopted relatively late for pancreatic procedures due to their complexity. Today, minimally-invasive distal pancreatectomy is the procedure of choice for the treatment of benign or premalignant pancreatic lesions due to the advantages inherent to laparoscopy. Data on the efficacy of minimally-invasive distal pancreatectomy in oncologic surgery is still limited and larger prospective series are needed prior to its widespread use for the treatment of pancreatic cancer. This review addresses various aspects of distal pancreatectomy, with emphasis on recent developments and open controversies.

Background and Aim Pancreatic ductal adenocarcinoma (PDAC) is characterized by aggressive biology and poor prognosis even after resection. Long-term survival is very rare and cannot be reliably predicted. Experimental data suggest an important role of epithelial-mesenchymal transition (EMT) in invasion and metastasis of PDAC. Tumor budding is regarded as the morphological correlate of local invasion and cancer cell dissemination. The aim of this study was to evaluate the biological and prognostic implications of EMT and tumor budding in PDAC of the pancreatic head. Methods Patients were identified from a prospectively maintained database, and baseline, operative, histopathological, and follow-up data were extracted. Serial tissue slices stained for Pan-Cytokeratin served for analysis of tumor budding, and E-Cadherin, Beta-Catenin, and Vimentin staining for analysis of EMT. Baseline, operative, standard pathology, and immunohistochemical parameters were evaluated for prediction of long-term survival (≥ 30 months) in uni- and multivariate analysis. Results Intra- and intertumoral patterns of EMT marker expression and tumor budding provide evidence of partial EMT induction at the tumor–host interface. Lymph node ratio and E-Cadherin expression in tumor buds were independent predictors of long-term survival in multivariate analysis. Conclusions Detailed immunohistochemical assessment confirms a relationship between EMT and tumor budding at the tumor–host interface. A small group of patients with favorable prognosis can be identified by combined assessment of lymph node ratio and EMT in tumor buds.

The incidence of cystic neoplasms of the pancreas (CNP) is steadily increasing, most likely due to the commonly increased use of cross-sectional abdominal imaging. Most of these lesions are benign at the time of initial presentation, but some harbor malignant potential that either requires constant surveillance or surgical resection. However, it is still unclear when resection is mandated and when observation is sufficient. Moreover, the extent of resection and the technique used are also a matter of debate since limited resection and minimally invasive procedures are becoming more popular. Therefore, the aim of this review was to assess the role of surgery for the management of CNPs with an emphasis on novel procedures.

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.

Im Verlauf einer nekrotisierenden Pankreatitis kommt es oft zu einer interventionspflichtigen Superinfektion der zuvor sterilen Nekroseareale. Die Nekrosen konnen auch dauerhaft als »walled-off pancreatic necrosis« (WOPN) bestehen bleiben. Bis vor wenigen Jahren erfolgte die Behandlung mittels offener Nekrosektomie mit einer hohen Morbiditat und Mortalitat. Seit einigen Jahren wird nach dem Step-up-Konzept zunachst interventionell drainiert und eine chirurgische Therapie nur falls notwendig durchgefuhrt. Diese erfolgt in der Regel als minimalinvasive transgastrale oder retroperitoneoskopische Nekrosektomie. Die offene Operation wird meist nur noch zur Beherrschung schwerwiegender Komplikationen (Blutung, Hohlorganperforation, Ischamie) eingesetzt.

Hintergrund und Ziel der Arbeit Trotz des hohen technischen Anspruchs werden minimalinvasive Operationsverfahren bei der Behandlung von Erkrankungen des Pankreas zunehmend eingesetzt. Daher gewinnt die Frage, ob diese Verfahren onkologisch sicher und chirurgisch sinnvoll sind, an Bedeutung. In diesem Ubersichtsbeitrag sollen diese Fragen auf dem Boden der hierzu publizierten Literatur beantwortet werden.

Postpancreatectomy hemorrhage is a rare but often severe complication after pancreatic resection. The aim of this retrospective study was to define incidence and risk factors of postpancreatectomy hemorrhage and to evaluate treatment options and outcome. Clinical data was extracted from a prospectively maintained database. Descriptive statistics, univariate and multivariate risk factor analysis by binary logistic regression were performed with SPSS software at a significance level of p = 0.05. N = 1,082 patients with pancreatic resections between 1994 and 2012 were included. Interventional angiography was successful in about half of extraluminal bleeding. A total of 78 patients (7.2 %) had postpancreatectomy hemorrhage (PPH), and 29 (2.7 %) were grade C PPH. Multivariate modeling disclosed a learning effect, age, BMI, male sex, intraoperative transfusion, portal venous and multivisceral resection, pancreatic fistula and preoperative biliary drainage as independent predictors of severe postpancreatectomy hemorrhage. High-risk histopathology, age, transfusion, pancreatic fistula, postpancreatectomy hemorrhage and pancreatojejunostomy in pancreatoduodenectomies were independent predictors of mortality. Our study identifies clinically relevant risk factors for postpancreatectomy hemorrhage and mortality. Interventional treatment of extraluminal hemorrhage is successful in about half of the cases and if unsuccessful constitutes a valuable adjunct to operative hemostasis. Based on our observations, we propose a treatment scheme for PPH. Risk factor analysis suggests appropriate patient selection especially for extended resections and pancreatogastrostomy for reconstruction in pancreatoduodenectomy.

Hintergrund Aufgrund des zunehmenden klinischen Einsatzes moderner Schnittbildgebung werden bisher seltene neuroendokrine Tumoren (NET) des Pankreas immer haufiger zufallig entdeckt. Klinisch werden funktionell inaktive von hormonell aktiven NET unterschieden. Sie werden als funktionell aktiv klassifiziert und nach dem durch sie produzierten Hormon benannt, wenn die Hormonproduktion spezifische Symptome verursacht.

Hintergrund: Zahlreiche präklinische Daten weisen auf Vorteile des laparoskopischen Operierens auch bei abdomineller Sepsisquelle und septischem Patienten hin. Methode und Ergebnisse: Anhand derzeit verfügbarer Literatur betrachten wir die Möglichkeiten und Limitierungen laparoskopischen Operierens beim septischen Patienten mit abdominellem Fokus. Neben generellen Überlegungen werden im Speziellen das Vorgehen bei Appendizitis, Cholezystitis, perforiertem Ulkus, Sigmadivertikulitis und akuter Pankreatitis erörtert. Schlussfolgerungen: Erfahrene laparoskopische Chirurgen können die Sanierung der abdominellen Sepsisquelle bei Appendizitis, Cholezystitis, perforiertem Ulkus oder auch Sigmadivertikulitis sicher durchführen. Kombinationen aus interventionellen Techniken und minimal invasiven Operationen bieten insbesondere bei der perforierten Sigmadivertikulitis und bei infizierten Pankreasnekrosen innovative Ansätze, die derzeit in multizentrischen prospektiven Studien untersucht werden.