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Pancreatic ductal adenocarcinoma cancer (PDAC) is a highly lethal malignancy requiring efficient detection when the primary tumor is still resectable. We previously developed the MxPancreasScore comprising 9 analytes and serum carbohydrate antigen 19-9 (CA19-9), achieving an accuracy of 90.6%. The necessity for 5 different analytical platforms and multiple analytical runs, however, hindered clinical applicability. We therefore aimed to develop a simpler single-analytical run, single-platform diagnostic signature.We evaluated 941 patients (PDAC, 356; chronic pancreatitis [CP], 304; nonpancreatic disease, 281) in 3 multicenter independent tests, and identification (ID) and validation cohort 1 (VD1) and 2 (VD2) were evaluated. Targeted quantitative plasma metabolite analysis was performed on a liquid chromatography-tandem mass spectrometry platform. A machine learning-aided algorithm identified an improved (i-Metabolic) and minimalistic metabolic (m-Metabolic) signatures, and compared them for performance.The i-Metabolic Signature, (12 analytes plus CA19-9) distinguished PDAC from CP with area under the curve (95% confidence interval) of 97.2% (97.1%-97.3%), 93.5% (93.4%-93.7%), and 92.2% (92.1%-92.3%) in the ID, VD1, and VD2 cohorts, respectively. In the VD2 cohort, the m-Metabolic signature (4 analytes plus CA19-9) discriminated PDAC from CP with a sensitivity of 77.3% and specificity of 89.6%, with an overall accuracy of 82.4%. For the subset of 45 patients with PDAC with resectable stages IA-IIB tumors, the sensitivity, specificity, and accuracy were 73.2%, 89.6%, and 82.7%, respectively; for those with detectable CA19-92 U/mL, 81.6%, 88.7%, and 84.5%, respectively; and for those with CA19-937 U/mL, 39.7%, 94.1%, and 76.3%, respectively.The single-platform, single-run, m-Metabolic signature of just 4 metabolites used in combination with serum CA19-9 levels is an innovative accurate diagnostic tool for PDAC at the time of clinical presentation, warranting further large-scale evaluation.

Introduction: Studies on pancreatic neuroendocrine tumors (PanNETs) regarding loss of ATRX, DAXX, or frequency of microsatellite instability (MSI) show inconclusive results. So far, data on corresponding metastaseshave not been published. Methods: We performed immunohistochemistry (IHC) of ATRX, DAXX, MSH2, MSH6, MLH1, and PMS2 on 74 PanNETs and 19 metastases. ATRX- and DAXX-negative PanNETs were further sequenced for mutations. We used polymerase chain reaction for MSI on cases with IHC loss of MSH2, MSH6, MLH1, and PMS2. Results: Immunohistochemical loss of DAXX and ATRX was observed in 8/74 (11%) and 6/74 (8%) PanNETs. Loss of DAXX immunoreactivity was statistically associated with higher tumor grade and showed a tendency toward a decreased overall survival. Sequencing of DAXX- (7/11 [64%]) and ATRX-negative (5/11 [45%]) PanNETs revealed a mutation in 6/7 (86%) and 2/5 (40%). The specificity of immunohistochemical loss of DAXX and ATRX for mutation was 80% and 67%, respectively. The expression status of DAXX compared to primary tumor differs in 2/12 (17%) lymph node metastases. We further identified 3/74 (4%) tumors as MSI, associated with a poor prognosis. Discussion/Conclusion: Our study supports the hypothesis that a loss of DAXX immunoreactivity can identify a more aggressive subtype of PanNET with high confidence, while ATRX loss is a weaker indicator. Our results also strengthen the role of DAXX immunolabeling as a prognostic marker. We could show that ATRX might be less suitable as a surrogate for sequencing. Our results indicate that IHC of DAXX and ATRX may identify PanNET subtypes as targets for more aggressive therapy.

Introduction: Studies on mind-body approaches in patients with advanced pancreatic ductal adenocarcinoma (PDAC) are rare. We performed a pilot study with follow-up until one year to explore changes in pain, quality of life (QoL), stress, and negative emotions in patients with advanced PDAC, who regularly practiced a standardized form of spiritual meditation in addition to standard medical care. Methods: At baseline and every two months for a maximum of one year, global pain, QoL (global, SEIQoL, FACT-G), spiritual well-being (FACIT-Sp), perceived stress (PSQ-20), anxiety and depression (HADS), and diurnal cortisol secretion (cortisol slope) were assessed. Changes from baseline were explored by pairwise comparisons of available cases. Results: 20 participants (11 women, 62 ± 9.9 SD years) participated in the study, of whom 9 patients survived the study year. Pairwise comparisons revealed transient improvements of pain after 4 and 6 months (both p-values < .05), of global QoL after 4, 6, 8, 10 months (all p-values < .05), of SeiQoL scores after 4 months (p < .05), of FACT-G scores after 6 months (p < .05), and of FACIT-Sp scores after 2 and 6 months (both p-values < .05). Furthermore, overall stress levels (PSQ-20) decreased from baseline to 2, 6, and 8 months (all p-values < .05), and anxiety declined from baseline to 6 months (p < .05). Depression scores and the cortisol slope did not change. Conclusion: This pilot study demonstrated the acceptability and feasibility of studies on spiritual meditation in patients with advanced PDAC. Randomized controlled trials are warranted to study the effects of spiritual meditation and other mind-body interventions on pain, quality of life, and emotional well-being in this patient population.

ZusammenfassungAufgrund einer steigenden Inzidenz nehmen Pankreasneoplasien, welche hauptsächlich Adenokarzinome, neuroendokrine und zystische Neoplasien umfassen, im klinischen Alltag eine zunehmende Relevanz ein.Auf Grundlage einer systematischen Literaturrecherche wurden von Pankreasexperten im Auftrag der DGAV zur Verbesserung der Indikationsqualität evidenzbasierte Empfehlungen zur Indikationsstellung bei Pankreasneoplasien erarbeitet.Eine eindeutige Operationsindikation besteht bei primär oder sekundär resektablen Pankreaskarzinomen ohne Metastasierung, bei funktionell aktiven sowie über 2 cm großen funktionell inaktiven neuroendokrinen Neoplasien und bei symptomatischen oder malignitätsverdächtigen zystischen Pankreasneoplasien einschließlich intraduktaler papillär-muzinöser Neoplasien (IPMN) vom Hauptgang und vom Mischtyp, muzinös-zystischer Neoplasien (MCN) > 4 cm und solid pseudopapillärer Neoplasien (SPN). Eine Operation kann bei Pankreaskarzinomen mit isolierter arterieller Gefäßinfiltration oder über längere Zeit stabiler Oligometastasierung im Rahmen von neuroendokrinen Neoplasien zur Metastasen- oder Debulkingchirurgie sowie bei Seitengang-IPMN mit Risikokriterien und MCN < 4 cm indiziert sein. Keine primäre Operationsindikation ergibt sich bei lokal fortgeschrittenen und metastasierten Pankreaskarzinomen oder serös-zystischen Neoplasien (SCN).Insgesamt sollte die Operationsindikationsstellung individualisiert unter Berücksichtigung von Alter, Komorbiditäten und Patientenwunsch erfolgen.

Background Current guidelines discourage surgery for serous cystic neoplasms (SCN) of the pancreas, because of their benign character, slow growth, and excellent prognosis. Nevertheless, SCN continue to contribute up to 30% of resected cystic pancreatic lesions worldwide. Methods Spectrum of indications and outcomes of surgery were analysed in a retrospective series of 133 SCN at a single high-volume center in Germany between 2004 and 2019. Results Relevant symptoms justified surgery in 60% of patients with SCN, while 40% underwent surgery because of preoperative diagnostic uncertainty about suspected malignancy. There were 4 malignant SCN (3%). Ninety-day mortality was 0.75%, major morbidity - 15%, 10-year survival - 95%. Risks of malignant transformation and of postoperative mortality were similarly low. Conclusions Surgery is reasonable and safe for symptomatic patients with SCN. Preoperative diagnostic uncertainty is the main reason for futile resections of benign asymptomatic SCN. Conservative management with close initial surveillance should be the first choice for this population. Surgery for supposed SCN without symptoms is justified only in carefully selected patients with suspected malignancy.

Pancreatic ductal adenocarcinoma (PDAC) has the worst prognosis of all malignant tumors due to unavailable screening methods, late diagnosis with a low proportion of resectable tumors and resistance to systemic treatment. Complete tumor resection remains the cornerstone of modern multimodal strategies aiming at long-term survival. This study was performed to investigate the overall rate of long-term survival (LTS) and its contributing factors.This was a retrospective single-center analysis of consecutive patients undergoing pancreaticoduodenectomy (PD) for PDAC between 2007 and 2014 at the St. Josef Hospital, Ruhr University Bochum, Germany. Clinical and laboratory parameters were assessed and evaluated for prediction of LTS with Cox regression analysis.The overall rate of LTS after PD for PDAC was 20.4% (34/167). Median survival was 24 months regardless of adjuvant treatment. Carbohydrate antigen 19-9 levels, tumor grade, lymph vessel invasion, perineural invasion and reduced general condition were significantly associated with LTS in univariate analysis (P0.05). Serum levels of carbohydrate antigen 19-9, American Joint Committee on Cancer stage, tumor grade, abdominal pain, male, exocrine pancreatic insufficiency and duration of postoperative hospital stay were independent predictors of cancer survival in multivariable analysis.Cancer related characteristics are associated with LTS in multimodally treated patients after curative PDAC surgery.

Bei den malignen soliden pseudopapillaren Neoplasien (SPN) handelt es sich um eine seltene Tumorentitat des Pankreas. Die Prognose der SPN ist generell exzellent, allerdings haben einige Tumoren ein malignes Potenzial und neigen zur Metastasierung bzw. zum Rezidiv. Untersucht werden soll, ob es histopathologische oder operationstechnische Risikofaktoren gibt, die das biologische Potenzial von SPN einschatzen lassen. Das Patientenkollektiv aus 2 grosen deutschen Pankreaszentren aus den Jahren 2009 bis 2018 wird in Bezug auf das Vorkommen von SPN, das chirurgische Management, histopathologische Tumorcharakteristika und das postoperative Outcome evaluiert. Es wurden 22 Patienten (17 Frauen, 5 Manner) mit SPN operiert. Das Alter der Patienten lag im Median bei 37 Jahren (Range 19–69 Jahre). Zum Zeitpunkt der Resektion zeigten 20 Patienten ein auf das Pankreas begrenztes Tumorwachstum. Eine Patientin mit Rezidiv einer auswarts resezierten SPN wies einen Lymphknotenbefall auf. Eine weitere Patientin hatte ein hepatisch metastasiertes Rezidiv (Union Internationale contre Cancer (UICC)-Stadium IV) einer auswartig resezierten SPN. Wahrend samtliche Patienten im Rahmen des Follow-ups rezidivfrei uberlebten, entwickelte diese Patientin erneut Leberfiliae. Die Uberlebensrate bis zum Ende des Follow-ups (Median 43 Monate; Range 1–132 Monate) dieser Studie lag bei 100 %. Es mangelt an Kenntnissen bezuglich moglicher Parameter, die das biologische Verhalten von SPN vorhersagen lassen. Auser einer erhohten Rezidivwahrscheinlichkeit nach Resektion eines SPN-Rezidives liesen sich am untersuchten Patientenkollektiv keine klaren Risikofaktoren ausmachen, die auf ein gesteigertes malignes Potenzial und ein moglicherweise schlechteres Outcome hinweisen konnten. Nur eine radikale operative Resektion mit Lymphadenektomie ermoglicht eine sichere Abschatzung des Tumorstadiums und eine Entfernung moglicherweise betroffener Lymphknoten, die beim Belassen Ursache eines Rezidivs sein konnten.

Das Institut fur Qualitat und Wirtschaftlichkeit im Gesundheitswesen (IQWiG) hat im Auftrag des Gemeinsamen Bundesausschuss (G‑BA) eine systematische Literaturrecherche und Evidenzbewertung zum Zusammenhang zwischen der Leistungsmenge und der Qualitat des Behandlungsergebnisses bei komplexen Eingriffen am Organsystem Pankreas durchgefuhrt und die Ergebnisse im Rapid Report V19-03 dargestellt. Der Bericht stellt einen Zusammenhang zwischen der Leistungsmenge und der Qualitat des Behandlungsergebnisses zugunsten von Krankenhausern bzw. Arztinnen und Arzten mit hoher Leistungsmenge fest. Ein Statement in Bezug auf Mindestmengen bei komplexen Pankreaseingriffen wird jedoch nicht gegeben. Die chirurgische Arbeitsgemeinschaft Leber, Galle, Pankreas (CALGP) der Deutschen Gesellschaft fur Allgemein- und Viszeralchirurgie (DGAV) nimmt hierzu Stellung.

Background: Pancreatic Ductal Adenocarcinoma (PDAC) lacks effective treatment options beyond chemotherapy. Although molecular subtypes such as classical and QM (quasi-mesenchymal)/basal-like with transcriptome-based distinct signatures have been identified, deduced therapeutic strategies and targets remain elusive. Gene expression data show enrichment of glycolytic genes in the more aggressive and therapy resistant QM subtype. However, whether the glycolytic transcripts are translated into functional glycolysis that could further be explored for metabolic targeting in QM subtype is still not known. Methods: We used different patient-derived PDAC model systems (conventional and primary patient derived cells, patient derived xenografts (PDX) and patient FFPE samples) and performed transcriptional and functional metabolic analysis. These included: RNAseq and Illumina HT12 bead array, in vitro Seahorse metabolic flux assays and metabolic drug targeting, and in vivo hyperpolarized [1-13C]pyruvate and [1-13C]lactate magnetic resonance spectroscopy (HP-MRS) in PDAC xenografts. Results: We found that glycolytic metabolic dependencies are not unambiguously functionally exposed in all QM PDACs. Metabolic analysis demonstrated functional metabolic heterogeneity in patient-derived primary cells and less so in conventional cell lines independent of molecular subtype. Importantly, we observed that the glycolytic product lactate is actively imported in the PDAC cells and used in mitochondrial oxidation in both classical and QM PDAC cells, although more actively in the QM cell lines. By using hyperpolarized 13C-magnetic resonance spectroscopy (HP-MRS), we were able to non-invasively identify highly glycolytic PDAC xenografts by detecting the last glycolytic enzymatic step and prominent intra-tumoral [1‑13C]pyruvate and [1-13C]lactate interconversion in vivo.Conclusion: Our study adds functional metabolic phenotyping to transcriptome-based analysis and proposes a functional approach to identify highly glycolytic PDACs as candidates for anti-metabolic therapeutic avenues.

Zusammenfassung Einleitung Pankreasresektionen werden bei schwerwiegenden Pankreaserkrankungen durchgeführt. Bei Komplikationen einer chronischen Pankreatitis, teilweise jedoch auch bei Raumforderungen, kann eine Pankreasteilresektion sinnvoll sein. Eine totale Pankreatektomie führt zum absoluten Insulinmangel und der Notwendigkeit einer Insulintherapie. Bei Teilresektionen (partielle Pankreatektomie) werden weniger gravierende Konsequenzen für den Glukosemetabolismus erwartet. Es ist das Ziel der vorliegenden Arbeit, die Insulinregime nach Pankreatektomie mit denen anderer Diabetesformen zu vergleichen. Material und Methodik Es wurden Patientencharakteristika und Details der postoperativen Insulintherapie von pankreasoperierten Patienten einer spezialisierten Universitätsklinik für Viszeralchirurgie ausgewertet. Diese Daten wurden mit Kohorten nicht operierter Patienten mit Typ-1-Diabetes (T1DM; absoluter Insulinmangel) bzw. Typ-2-Diabetes (T2DM; Insulinresistenz und relativer Insulinmangel), jeweils unter Insulintherapie, verglichen. Ergänzt wurde diese Datenanalyse durch eine Literaturrecherche zu den Stichworten „pancreatogenic diabetes“, „type 3c diabetes“ und „pancreatectomy diabetes“. Ergebnisse Daten von 32 (68,8 % Frauenanteil) bzw. 41 (43,9 % Frauenanteil) Patienten nach totaler bzw. partieller Pankreatektomie wurden analysiert. Vor der totalen Pankreatektomie hatten 56,3 % der Patienten einen Diabetes mellitus, postoperativ bestand bei allen Patienten eine Insulinpflichtigkeit. Dabei waren die Insulindosierungen im Vergleich mit Patienten mit T1DM (unter intensivierter Insulintherapie) signifikant niedriger (p Diskussion Der basale und prandiale Insulinbedarf nach Pankreatektomie ist niedriger als bei einem T1DM und einem T2DM. Dies sollte bei der Blutzuckereinstellung nach Pankreatektomie berücksichtigt werden.

ObjectiveChronic pancreatitis (CP) is a fibroinflammatory syndrome leading to organ dysfunction, chronic pain, an increased risk for pancreatic cancer and considerable morbidity. Due to a lack of specific biomarkers, diagnosis is based on symptoms and specific but insensitive imaging features, preventing an early diagnosis and appropriate management.DesignWe conducted a type 3 study for multivariable prediction for individual prognosis according to the TRIPOD guidelines. A signature to distinguish CP from controls (n=160) was identified using gas chromatography-mass spectrometry and liquid chromatography‐tandem mass spectrometry on ethylenediaminetetraacetic acid (EDTA)-plasma and validated in independent cohorts.ResultsA Naive Bayes algorithm identified eight metabolites of six ontology classes. After algorithm training and computation of optimal cut-offs, classification according to the metabolic signature detected CP with an area under the curve (AUC) of 0.85 ((95% CI 0.79 to 0.91). External validation in two independent cohorts (total n=502) resulted in similar accuracy for detection of CP compared with non-pancreatic controls in EDTA-plasma (AUC 0.85 (95% CI 0.81 to 0.89)) and serum (AUC 0.87 (95% CI 0.81 to 0.95)).ConclusionsThis is the first study that identifies and independently validates a metabolomic signature in plasma and serum for the diagnosis of CP in large, prospective cohorts. The results could provide the basis for the development of the first routine laboratory test for CP.

BACKGROUND: Perforated marginal ulcers (PMUs) are a feared long-term complication following pancreaticoduodenectomy (PD), which always require relaparotomy compared to marginal ulcers. METHODS: First, we performed a retrospective chart review for all patients who underwent PD from 2007–2016 to identify incidence and risk factors associated with PMUs. Second, we analyzed follow up gastroscopies in all patients undergoing PD from 2007–2011 to identify the overall incidence of marginal ulcers. RESULTS: A total of 725 patients underwent PD in the retrospective study period. 17 patients (2.3%) suffered from PMU at a median postoperative time of 13 months. These patients were significantly younger (median age: 49 vs. 62 years; P=0.02) and suffered most often from chronic pancreatitis (P

ZusammenfassungHintergrund Im Jahr 1976 gründete sich die Selbsthilfeorganisation „Arbeitskreis der Pankreatektomierten e. V.“ (AdP). Sie ist mit über 1000 Mitgliedern die mit Abstand größte Gruppe von Betroffenen mit Pankreaserkrankungen in Deutschland. AdP-Mitgliedern kommt aufgrund ihrer Betroffenenkompetenz eine bedeutende Unterstützungsfunktion für Ratsuchende zu. Die vorliegende, von Patienten veranlasste Querschnitts- und Versorgungsforschungsstudie hat das Ziel, Ergebnisse nach Pankreasoperationen aus Patientensicht zu erheben.Methode Allen Mitgliedern des AdP wird seit dem 03.03.2018 ein Fragebogen zu 11 Themenkomplexen zugestellt. Die Daten werden in eine pseudonymisierte Datenbank aufgenommen.Ergebnisse 625 pankreasoperierte Patienten nahmen an der Studie teil (Rücklaufquote 55,4 %). 57,5 % erhielten Pankreaskopfresektionen, 15,5 % Pankreaslinksresektionen, 23,2 % Pankreatektomien und 4,0 % einen sonstigen oder nicht spezifizierten Eingriff. Bei 37,9 % wurde ein Pankreaskarzinom diagnostiziert, bei 38,2 % ein sonstiger Pankreastumor, bei 25 % eine Pankreatitis, bei 4 % eine Autoimmunpankreatitis und bei 2,7 % andere seltene Erkrankungen. Ein Teil der Patienten hatte mehr als eine Pankreaserkrankung.Unter den 237 operierten Pankreaskarzinompatienten lebten 82 Patienten länger als 5 Jahre und davon 41 Patienten länger als 10 Jahre. 24,5 % der Karzinompatienten hatten Zweitkarzinome und 13,9 % nahe Verwandte mit einem Pankreaskarzinom.Nach Pankreasoperationen war der Gewichtsverlust eingriffsabhängig beträchtlich, am größten perioperativ nach Pankreatektomie (17,8 ± 9,5 kg). Die Diabetesprävalenz betrug 54,1 %, die Inzidenz perioperativer Diabetesneuerkrankungen 33,3 %. 91,5 % benötigten postoperativ eine Lipasesubstitution im Mittel von 189 417 IE/Tag. Die Lebensqualität (körperlich/seelisch/sozial) zeigte sich von der Operationsart unabhängig.Schlussfolgerung Patienten nach komplexen Pankreasresektionen sind zeitlebens mit Einschränkungen im täglichen Leben konfrontiert. Selbsthilfeorganisationen wie der AdP können einen wichtigen, jedoch bislang wenig genutzten Beitrag zur Erforschung dieser Erkrankungen leisten, und zwar einerseits durch den Perspektivwechsel, andererseits durch Generierung großer Patientenkollektive, z. B. die sehr große Gruppe der Langzeitüberlebenden.

694 Background: Perioperative chemotherapy (CTX) in resectable pancreatic adenocarcinoma (rPDAC) is still not considered SoC and data regarding efficacy but also quality of life (QoL) are limited. NEONAX is a prospective, randomized phase II trial in patients with rPDAC with two independent experimental arms examining perioperative (2 pre- and 4 postoperative cycles, arm A) or adjuvant (6 cycles, arm B) of Gem (1000mg/m2) and nab-P (125mg/m2) on days 1,8,15 of a 28-day cycle. The primary endpoint DFS at 18 mo. as well as DFS, OS and safety have already been reported. Here we present the QoL data of the NEONAX trial. Methods: QoL was evaluated by EORTC QLQ-C30, EORTC QLQ-PAN26 and HADS-D questionnaires at baseline, at the beginning of each CTX cycle (neoadj. and adj. in arm A, only adj. in arm B), after neoadj. treatment in arm A as well as prior and post resection and after 6 cycles of CTX. Results: Global health status score (GHS-score) (QLQ-C30) showed no difference between baseline (t1) and the timepoint after 6 cycles of CTX (t2) in the perioperative arm A (66.7/100 at both timepoints). Here patients experienced the lowest GHS-score pre- and postoperatively (50/100 in both cases). Adjuvant arm B showed a deterioration in the GHS-score of 12.5 points from timepoint 1 to 2 (62.5/100 to 50.0/100). Here the lowest GHS-score was observed within 4 weeks post-surgery (41.7/100). Physical function score (QLQ-C30) was decreased by 6.7 points (86.7/100 to 80/100) in perioperative arm A and by 26.7 points (86.7/100 to 60/100) in arm B between both timepoints. Role function (QLQ-C30) was reduced by 16.7 points (83.3/100 to 66.7/100) in arm A and by 33.3 points (83.3/100 to 50/100) in arm B between both timepoints. In the remaining subscales of the used questionnaires the two arms of the trial showed comparable median scores over the whole study period. The number of submitted questionnaires at each timepoint varied but was at large comparable in both arms. Conclusions: QoL was largely preserved in the perioperative as well as the adjuvant arm of the NEONAX trial. GHS-score was lower pre-and postoperatively in arm A. The lowest GHS-score was observed postoperatively in the adjuvant arm B. QoL was restored at the end of the treatment period in the perioperative arm A and remained slightly reduced in arm B suggesting that QoL is not substantially impaired by perioperative treatment in rPDAC. Clinical trial information: NCT02047513 . [Table: see text]

The incidence of pancreatic ductal adenocarcinoma is continuously increasing and will become the second leading cause of cancer-related death in Europe and the USA by 2030. With a 5-year overall survival rate of less than 10% the prognosis remains poor. So far surgical tumor resection remains the only curative treatment option, which is now partially supported by multimodal neoadjuvant and adjuvant therapy concepts. Due to the aggressive tumor biology patients with advanced pancreatic cancer in particular can profit from these multimodal therapy concepts. Additionally, in recent years surgical treatment was optimized, the criteria for tumor resectablity were defined and minimally invasive surgery was widely introduced. This review article summarizes the newest developments and the new German S3 guidelines concerning surgery of pancreatic cancer.Die Inzidenz des duktalen Adenokarzinoms des Pankreas steigt weiterhin und es wird bis 2030 zur zweithäufigsten krebsbedingten Todesursache in Europa und den USA aufsteigen. Mit einer 5‑Jahres-Überlebensrate von nur bis zu 10 % hat es weiterhin eine sehr schlechte Prognose. Die chirurgische Tumorresektion stellt die einzige kurative Therapieoption dar, die inzwischen zum Teil durch multimodale neoadjuvante und adjuvante Therapiekonzepte unterstützt wird. Aufgrund der aggressiven Tumorbiologie können Patienten insbesondere bei fortgeschrittenen Pankreaskarzinomen von diesen multimodalen Therapiekonzepten profitieren. Daneben wurden in den letzten Jahren die chirurgische Therapie optimiert, die Resektabilität anhand verschiedener Kriterien klarer definiert und minimal-invasive Operationen in der Breite eingeführt. Die aktuelle Übersichtsarbeit fasst die neuesten Entwicklungen und die neue S3-Leitlinie zum Thema Chirurgie beim Pankreaskarzinom zusammen.

BACKGROUND: Aberrant right hepatic arteries (aRHA) are frequently encountered during pancreaticoduodenectomy (PD). Their effects on surgical morbidity and resection margin are still debated. This study aimed to compare the short term and long term outcomes in patients with and without aRHA. METHODS: A single-center retrospective analysis of 353 consecutive PD during a 5-year period was done. The type of arterial supply was determined preoperatively by CT and confirmed at surgery. Hiatt types III–VI included some type of aRHA and comprised the study group. Hiatt types I and II were considered irrelevant for PD and used as controls. Primary endpoints were the rates of major postoperative complications and the rate of R0-resection in cases of malignant disease. Secondary endpoints included duration of surgery, postoperative stay, number of harvested lymph nodes and survival in patients with pancreatic cancer. Own results were compared to existent data using a systematic review of the literature. RESULTS: No aRHA had to be sacrificed or reconstructed. Surgical morbidity and specific complications such as post-pancreatectomy hemorrhage (PPH), pancreatic fistula and bile leak were the same in patients with and without aRHA. There was no significant difference in operative time, blood loss, length of ICU- and hospital stay. Patients with malignancy had similar high rates of R0-resection and identical number of harvested lymph nodes. Survival of patients with pancreatic cancer was not affected by aRHA. CONCLUSIONS: aRHA may be preserved in virtually all cases of PD for resectable pancreatic head lesions without increasing surgical morbidity and without compromising oncological radicality in patients with cancer, provided the variant anatomy is being recognised on preoperative CT and a meticulous surgical technique is used.

3626 Background: CRC still is one of the leading causes of cancer related death though prognosis has improved through guideline based management. The COVID-19 pandemic lead to re-allocation of resources subordinating all sections of care for CRC patients. We present data on changes of CRC care during the pandemic from 22 German AIO CC and our high volume Institute of Pathology (pathology). Methods: Data was collected retrospectively comparing the months (mo) of the first wave (fw) (4-6/2020) and second wave (sw) (11-12/2020) of the pandemic with corresponding periods (cp) in 2019 focusing on the number of precancerous (ICD-O/0+2) and malignant (ICD-O/3+6) colorectal lesions (CRL) diagnosed by our pathology, the number/stage of primary diagnoses (PD) and the number of surgeries (surg) at AIO CC. There, quality criteria of CRC care were also assessed (number of PD discussed within a multidisciplinary tumor board (tb), received social service (soc)/ psychological (psy) counseling or recruited into a clinical trial). Statistical analysis was performed using students t-test for paired data. Results: Numbers of CRL detected upon histology (row 1-3), number of cases, surg and quality criteria from AIO CC (row 4-9) are displayed in the table. We saw a dip in diagnosed CRL and number of surg (p=0.007) only during fw, whereas PD dipped significantly in both waves. A significant reduction in diagnosis of stage III CRC was detected for 2019 vs. 2020 (p=0.001), not for other stages. Quality criteria showed a significant reduction in clinical trial inclusion, a small dip in soc/psy counseling and persistently high tb presentation. Conclusions: We detected a significant decrease of premalignant lesions and primary cancers during the first year of the pandemic which may impact cancer mortality in the future. Certified German CC provided CRC care with significant reduction in clinical trial inclusion only, suggesting high stability of established certified cancer care infrastructure.[Table: see text]

Purpose Chemotherapy with or without radiotherapy is the standard in patients with initially nonmetastatic unresectable pancreatic cancer. Additional surgery is in discussion. The CONKO-007 multicenter randomized trial examines the value of radiotherapy. Our interim analysis showed a significant effect of surgery, which may be relevant to clinical practice. Methods One hundred eighty patients received induction chemotherapy (gemcitabine or FOLFIRINOX). Patients without tumor progression were randomized to either chemotherapy alone or to concurrent chemoradiotherapy. At the end of therapy, a panel of five independent pancreatic surgeons judged the resectability of the tumor. Results Following induction chemotherapy, 126/180 patients (70.0%) were randomized to further treatment. Following study treatment, 36/126 patients (28.5%) underwent surgery; (R0: 25/126 [19.8%]; R1/R2/Rx [n = 11/126; 6.1%]). Disease-free survival (DFS) and overall survival (OS) were significantly better for patients with R0 resected tumors (median DFS and OS: 16.6 months and 26.5 months, respectively) than for nonoperated patients (median DFS and OS: 11.9 months and 16.5 months, respectively; p = 0.003). In the 25 patients with R0 resected tumors before treatment, only 6/113 (5.3%) of the recommendations of the panel surgeons recommended R0 resectability, compared with 17/48 (35.4%) after treatment (p Conclusion Tumor resectability of pancreatic cancer staged as unresectable at primary diagnosis should be reassessed after neoadjuvant treatment. The patient should undergo surgery if a resectability is reached, as this significantly improves their prognosis.

We previously reported 2 cases of pathologic complete response (pCR) of a pancreatic cancer (PC) following neoadjuvant FOLFIRINOX treatment. We now complete our report by a follow-up on both patients. Patient 1 achieved a disease-free survival of 12 months after initial resection until she developed a singular hepatic metastasis. Treatment by FOLFIRINOX and complete removal of the metastasis by atypical liver resection after 6 months allowed for another 12 months of disease control. After intra-abdominal tumor recurrence and development of intracerebral metastases, the patient died 34 months after primary diagnosis. Patient 2 developed hepatic tumor recurrence only 3 months after initial resection. However, treatment by FOLFIRINOX led to a stable disease for 27 months after resection and was followed by atypical liver resection of multiple segments. Six months later, another hepatic recurrence was suspected. Via next-generation sequencing (NGS) of the tumor genome, a deleterious mutation in the ataxia telangiectasia-mutated (ATM) gene, causing a BRCAness, was detected. After initial treatment by FOLFOX, maintenance therapy with the poly-ADP-ribose-polymerase (PARP) inhibitor olaparib was initiated. The patient is now alive for 54 months after initial diagnosis of metastasized pancreatic adenocarcinoma. Tumor recurrence is possible even after pCR of PC and remains challenging. In case of multifocal tumor recurrence, chemotherapy remains the standard treatment. Recently, genetic sequencing allows individualized treatments. In selected cases, highly specialized teams can offer a variety of therapeutic options leading to previously unseen clinical courses.

ZusammenfassungDie chronische Pankreatitis stellt eine über die Jahre rezidivierende Erkrankung mit wiederkehrenden Entzündungsschüben der Bauchspeicheldrüse und gürtelförmigen Oberbauchschmerzen dar. Unbehandelt führt die chronische Pankreatitis zu rezidivierenden Schmerzen, die letztendlich häufig eine Therapie mit Opiaten erfordern. Die chronische Pankreatitis führt zu rezidivierenden Krankenhausaufenthalten der Betroffenen sowie zu sozioökonomischen Nachteilen für die Patienten. Im Verlauf kann es zu lokalen Folgen der chronischen Pankreatitis kommen wie Pseudozystenbildung, Gallengangstenose, Duodenalobstruktion oder portaler Hypertension. Ziel dieses Artikels ist die Darstellung der Indikationen zur chirurgischen Therapie für die chronische Pankreatitis. Zugrunde liegend ist eine systematische Literaturrecherche und Bewertung, die Erstellung von Schlüsselfragen nach dem PICO-Prinzip und die Evaluation der Indikationen in einem 3-stufigen Delphi-Verfahren unter den Mitgliedern der Arbeitsgruppe Pankreas und der Arbeitsgruppe Indikationsqualität der Deutschen Gesellschaft für Allgemein- und Viszeralchirurgie. Die chirurgische Resektion des entzündlichen Pankreaskopftumors nach einem primär konservativen Therapieversuch stellt eine hocheffiziente Therapie zur Kontrolle der Schmerzen und zur Vermeidung von Komplikationen bei der chronischen Pankreatitis dar. Hierfür stehen gut evaluierte duodenumerhaltende (Operationen nach Frey, Bern, Beger) und duodenumresezierende Verfahren (pyloruserhaltende Pankreaskopfresektion, Whipple-Operation) sowie Drainageoperationen zur Verfügung. Protrahierung der chirurgischen Therapie bei Versagen eines initialen konservativen Therapieversuchs kann zur Chronifizierung von Schmerzen, Kachexie und Malnutrition des Patienten und zur Erhöhung der Komplikationen bei der chirurgischen Therapie führen.