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Background The effect of bacterobilia on morbidity after pancreatoduodenectomy remains unclear. The aim of this study was to examine the influence of positive intraoperative bile cultures and perioperative antibiotic prophylaxis on morbidity measured using the Comprehensive Complication Index, a weighted composite of postoperative complications. Methods Intraoperative bile cultures of 182 patients who underwent pancreatoduodenectomy were obtained. We examined the effect of intraoperative bile cultures and perioperative antibiotic prophylaxis on the Comprehensive Complication Index and the occurrence of postoperative complications. To this aim, we performed general linear models controlling for relevant demographic and perioperative factors. Results Positive (versus negative) intraoperative bile cultures were associated with a higher mean Comprehensive Complication Index (25.34 vs 16.81, P = .025). The mean Comprehensive Complication Index differed significantly between individuals with positive intraoperative bile cultures and bacterial strains not covered by perioperative antibiotic prophylaxis (26.2) versus positive intraoperative bile cultures and bacterial strains sensitive to perioperative antibiotic prophylaxis (22.7) (P = .045). Positive (versus negative) intraoperative bile cultures were associated with 4.75 times (95% confidence interval: 1.74–13.00, P = .002) greater odds of wound infections. The odds of wound infection were 1.93 times (95% confidence interval: .47–8.04) greater in those with positive intraoperative bile cultures and adequate perioperative antibiotic prophylaxis and 6.14 times (95% confidence interval: 2.17–17.35) greater in those with positive intraoperative bile cultures and inadequate perioperative antibiotic prophylaxis (versus negative intraoperative bile cultures) (P = .001). Conclusion Bacterobilia is associated with a significant increase in Comprehensive Complication Index and wound infections after pancreatoduodenectomy, which may be reduced by administration of a specific perioperative antibiotic prophylaxis. Acquisition of bile cultures sampled through the external conduit of patients with preoperative biliary drainage could help in selecting a specific perioperative antibiotic prophylaxis and patients with bile duct stents might benefit from broad spectrum perioperative antibiotic prophylaxis.

Resume Introduction L’etendue de la chirurgie pancreatique pour cancer rend la survenue de fuites chyleuses (FC) assez frequente. Recemment une definition consensuelle de FC a ete etablie par l’International Study Group of Pancreatic Surgery (ISGPS). Le but de cette etude etait d’analyser les facteurs de risque et le traitement des FC apres chirurgie pancreatique. Methodes Au total, 228 patients ayant un drainage sereux ou chyleux apres chirurgie pancreatique ont ete inclus dans cette etudes de donnees collectees prospectivement entre janvier 2014 et decembre 2016. Les facteurs de risque et les traitements des FC etaient compares. Une analyse du sous-groupe de patients ayant eu l’ablation des drains malgre une FC persistante etait effectuee avec une etude de la necessite d’un drainage percutane ou une reintervention dans les 3 mois postoperatoires. Resultats Soixante patients ayant eu une FC etaient analyses. Parmi eux, 41 ont eu un regime pauvre en graisses pendant une duree mediane de 12 jours. Le type de traitement n’avait pas d’effet sur la duree du drainage (p = 0,29) et la morbidite (p = 0,15). De plus la morbidite postoperatoire n’etait pas augmentee chez les patients ayant eu une ablation des drains malgre une FC persistante (p = 0,84). Aucun de ces patients n’avait eu un drainage percutane ou une reintervention pour collection postoperatoire. Conclusions Le regime pauvre en graisse n’est probablement pas un traitement efficace des FC. De futures etudes sont necessaires pour explorer l’effet et la necessite d’un traitement des FC.

Summary Purpose With increasing soft tissue clearance in pancreatic cancer surgery, postoperative chyle leak (CL) has become a more commonly observed complication. Recently, a new consensus definition was established by the International study group of pancreatic surgery (ISGPS). The aim of the present analysis was to evaluate risk factors and treatment options of patients with CL after pancreatic surgery. Methods Two hundred and twenty-eight patients with serous or chylous drainage after pancreatic surgery were included in this analysis of a prospectively collected database between 01/2014 and 12/2016. Risk factors for CL and treatment options were compared. A subgroup analysis on those patients, who had drain removal despite of persistent CL with respect to the need of subsequent percutaneous drainage or reoperation within three months postoperatively, was performed. Results Sixty patients with CL were identified. Of those, 41 patients were treated with medium-chain triglyceride-diet, with a median duration of therapy of 12 days. In patients with CL, the type of treatment had no effect on time to drain removal (P = 0.29) and morbidity (P = 0.15). Furthermore, morbidity was not increased in patients who had their drains removed despite persistent CL (P = 0.84). None of the latter patients had percutaneous drainage or reoperation for CL after removal of the surgical drains. Conclusions Dietary treatment may not be very effective in treating CL. Further research is warranted to explore the effect and necessity of CL treatment.

Objectives Pancreatic ductal adenocarcinoma (PDAC) represents a widespread form of malignant pancreatic neoplasms and a leading oncologic cause of death in Europe and the USA. Despite advances in understanding its molecular biology, the 5-year survival rate remains low at 10%. The extracellular matrix in PDAC contains proteins, including SPOCK2, which are essential for tumorigenicity and drug resistance. The present study aims to explore the possible role of SPOCK2 in the pathogenesis of PDAC. Materials and methods Expression of SPOCK2 was evaluated in 7 PDAC cell lines and 1 normal pancreatic cell line using quantitative RT-PCR. Demethylation of the gene was carried out using 5-aza-2'-deoxycytidine (5-aza-dC) treatment with subsequent validation Western Blot analysis. In vitro downregulation of SPOCK2 gene was performed using siRNA transfection. MTT and transwell assays were employed to evaluate the impact of the SPOK2 demethylation on the proliferation and migration of PDAC cells. KM Plotter was applied to analyze a correlation between SPOCK2 mRNA expression and the survival of PDAC patients. Results In contrast to the normal pancreatic cell line, SPOCK2 expression was significantly downregulated in PDAC cell lines. Treatment with 5-aza-dC, led to increase in SPOCK2 expression in the cell lines tested. Importantly, compared with control cells, transfected with SPOCK2 siRNA cells exhibited increased growth rates and more migration ability. Finally, we demonstrated that a high SPOCK2 expression level correlated with longer overall survival of patients with PDAC. Conclusion The expression of SPOCK2 is downregulated in PDAC as a result of hypermethylation of its corresponding gene. SPOCK2 expression as well as the demethylation of its gene could be a potential marker for PDAC.

Background To evaluate technical and clinical results of stent-graft (SG) placement for bleeding from the hepatic artery (HA). Methods All patients intended and treated with SG deployment for bleeding from the HA at single center from January 2012 to May 2020 were retrospectively identified, and procedural details, risk factors for rebleeding, SG occlusion and mortality were analyzed. Results Twenty-seven patients (mean age 68.8 ± 10.1) were identified, and 25 patients underwent 26 SG procedures. Twenty-four patients had recent surgery. The technical success rate was 92.8%. Three patients (3/25) had rebleeding (88% clinical success). Intensive-care need before the procedure (p = 0.013) and smaller stent-graft size (≤4 mm, p = 0.032) were related to clinical failure. Twenty-two patients had follow-up imaging. The SG maintained patency in 10 (45.4%) patients at the most recent imaging. Only placement of SG distal to the HA bifurcation (p = 0.012) was related to occlusion. The 30-day and in-hospital mortality rate after SG was 8% and 24%. In-hospital mortality was associated with the intraabdominal septic source (p = 0.010) and revision surgery (p = 0.001). Conclusion Stent-grafts are effective in the emergent treatment of HA bleeding. Mortality is mainly related to the general condition of the patient, and stent-grafts offer time to treat underlying medical problems sufficiently.

Das Kardinalsymptom der chronischen Pankreatitis ist ein sehr heftiger, gurtelformiger Oberbauchschmerz, der einer zeitnahen und suffizienten Behandlung bedarf. Daruber hinaus kommt es bei der chronischen Pankreatitis haufig zu Folgekomplikationen wie Pankreaspseudozysten, Pankreasgangsteinen und -stenosen sowie Gallenwegstenosen. Wahrend uber den Stellenwert von endoskopischen vs. chirurgischen Behandlungsverfahren sehr lange kontrovers diskutiert wurde, richten sich die Behandlungsverfahren der Wahl heute nach der Indikation und sind in der neuen S3-Leitlinie zur Pankreatitis klar formuliert. Es ist schon lange bekannt, dass chirurgische Verfahren den endoskopischen in der Therapie von Schmerzen bei chronischer Pankreatitis uberlegen sind. Dies wurde durch die erst kurzlich publizierte ESCAPE-Studie noch unterstrichen, in der eine fruhe chirurgische Intervention einem „step-up approach“ mit initialer Endoskopie uberlegen war. Somit ist zur kurzfristigen Schmerztherapie ein endoskopischer Therapieversuch zwar gerechtfertigt, mittel- und langfristig sollte jedoch ein operatives Verfahren zur Anwendung kommen. Im Gegensatz dazu konnen Pankreaspseudozysten, einzelne proximal gelegene Pankreasgangsteine sowie benigne Gallengangstenosen (auser bei kalzifizierender Pankreatitis) heute in der Regel endoskopisch gut beherrscht werden. Bei distal gelegenen Pankreasgangsteinen sowie symptomatischen Pankreasgangstenosen ist wiederum die chirurgische Therapie das Verfahren der Wahl. Der vorliegende Ubersichtsbeitrag diskutiert diese indikationsbezogenen Verfahren im Detail und erortert sie in enger Anlehnung an die kurzlich veroffentlichte neue S3-Leitlinie „Pankreatitis“ der Deutschen Gesellschaft fur Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS).

ObjectivesEarly patient disposition is crucial to prevent crowding in emergency departments (EDs). Our study aimed to characterise the need of in-house resources for patients treated in the ED according to the Emergency Severity Index (ESI) and the presenting complaint at the timepoint of triage.DesignA retrospective single-centre study was conducted.SettingData of all patients who presented to the interdisciplinary ED of a tertiary care hospital in Munich, Germany, from 2014 to 2017 were analysed.Participantsn=113 694 patients were included.MeasuresESI Score, medical speciality according to the chief complaint, mode of arrival, admission rates and discharge destination from the ED were evaluated.ResultsPatient disposition varied according to ESI scores in combination with the chief complaint. Patients with low ESI scores were more likely to be admitted after treatment in the ED than patients with high ESI scores. Highly prioritised patients (ESI 1) mainly required admission to an intensive care unit (ICU, 27%), intermediate care unit (IMC, 37%) or immediate intervention (11%). In this critical patient group, 30% of patients with neurological or medical symptoms required immediate intensive care, whereas only 17% of patients with surgical problems were admitted to an ICU. A significant number of patients (particularly with neurological or medical problems) required hospital (and in some cases even ICU or IMC) admission despite high ESI scores.ConclusionsOverall, ESI seems to be a useful tool to anticipate the need for specialised in-hospital resources on arrival. Patients with symptoms pointing at neurological or medical problems need particular attention as ESI may fail to sufficiently predict the care facility level for this patient group.

BACKGROUND Pancreatic panniculitis is an extremely rare condition associated with different underlying pancreatic disorders and characterized by subcutaneous fat necrosis induced by elevated serum lipase levels. These lesions usually affect the lower extremities and may precede abdominal symptoms of pancreatic disease. Acinar cell carcinoma (ACC) of the pancreas is a rare pancreatic neoplasm, accounting for only 1%-2% of pancreatic tumors in adults. CASE SUMMARY We present the case of a 72-year-old man with ACC of the pancreatic head and synchronous liver metastases. Both the primary tumor and liver metastases were resected. Serum lipase was elevated before surgery and decreased to normal postoperatively. Rising serum lipase levels at follow-up led to the diagnosis of hepatic recurrence. This disease progression was then accompanied by pancreatic panniculitis, with subcutaneous fat necrosis and acute arthritis. To the best of our knowledge, only 4 cases have been reported in the literature and each showed a similar association of serum lipase levels with pancreatic panniculitis and progression of ACC. CONCLUSION Clinical symptoms and progression of ACC may correlate with serum lipase levels, suggesting potential usefulness as a follow-up biomarker.

Neoadjuvant chemotherapy has become a powerful tool to convert borderline resectable (BRPC) and locally advanced pancreatic cancers (LAPC) into a resectable scenario. However, data analyzing the optimal type of therapy are scarce. In the present multicenter retrospective study, we evaluated the influence of FOLFIRINOX (FFX) and gemcitabine (GEM)-based neoadjuvant therapy on patient prognosis.Data on 239 patients from 7 centers across Europe was gathered using an online database. Patients having received their first cycle of chemotherapy for BRPC/LAPC before 06/2017, with a minimum follow-up of 12 months, were included in the intention-to-treat analysis.Patients treated with neoadjuvant FFX (n = 135) or gemcitabine + nab-paclitaxel (GNP) (n = 38) had significantly improved radiological response according to RECIST criteria as compared to single-agent GEM (n = 16), with a partial/complete response of 59.3%, 55.3% and 6.25% respectively (p = 0.001). Treatment with FFX (n = 135) and GNP (n = 38) resulted in higher resection rates compared to GEM (73.3%, 81.6% and 43.8%; p = 0.01 and p = 0.005). Regardless of regimen, patients who were resected had significantly prolonged overall survival compared to non-resected patients (p 0.01). Complete pathological responses (ypT0 ypN0) were predominantly observed with FFX (p = 0.01). Adjuvant GNP in addition to successful neoadjuvant therapy and surgery resulted in a trend towards improved median survival as compared to postoperative observation (47.0 vs. 30.1 months, p = 0.06).Representing one of the largest studies published so far, our results reveal that patients with BRPC/LAPC should be offered either FFX or GNP to improve chances of resection and with this also survival.

Surgical resection improves survival in pancreatic ductal adenocarcinoma (PDAC) and adjuvant chemotherapy adds an additional survival-benefit. While surgical technique has improved in recent years, it remains unclear whether these improvements translate into a survival benefit independent of adjuvant chemotherapy. Thus, we aimed to clarify whether survival of patients who were treated with either Gemcitabine (GEM) or who were observed only in randomized controlled trials on adjuvant chemotherapy of PDAC improved over time.A systematic search of MEDLINE/PubMed was performed to identify randomized controlled trials on adjuvant chemotherapy of PDAC. The search was limited to studies with arms on GEM monotherapy or postoperative observation and studies were grouped by the median year of enrolment and the use of GEM. Subsequently, a meta-regression on the effect of the median year of enrolment on patient survival was performed.A total of 13 studies with 2469 patients was included, with median years of enrollment ranging from 1996 to 2015. While disease-free survival decreased in patients with postoperative observation (18.0 vs. 5.0 months, p = 0.001), median survival improved over time in patients with postoperative observation (15.8 vs. 18.4 months, p = 0.01) and in patients treated with adjuvant GEM (22.8 vs. 35.0 months, p 0.001). One- (p ≤ 0.01) and two-year survival (p = 0.056) improved in both patients treated with adjuvant GEM and those observed only.Survival after surgical resection of PDAC has improved since 1996, even in patients who did not receive adjuvant chemotherapy. Improved surgical technique and postoperative management are likely to be causative factors.

Im aktuellen klinischen Alltag haben zystische Pankreaslasionen (PCNs) einen zunehmend relevanten Stellenwert, da sie aufgrund der sich stetig verbessernden Bildgebung haufig als Zufallsbefund diagnostiziert werden. Man unterscheidet zwischen nichtneoplastischen und neoplastischen Pankreaszysten, wobei letztere in unterschiedlicher Auspragung zur malignen Entartung neigen und damit als Vorlauferlasionen des duktalen Adenokarzinoms des Pankreas (PDAC) gelten. Zur Differenzialdiagnose werden neben einer genauen Anamnese und Untersuchung vor allem bildgebende Verfahren wie die Computertomographie (CT) und Magnetresonanztomographie (MRT) sowie der endoskopische Ultraschall mit Feinnadelaspiration herangezogen. Die Indikationen zur chirurgischen Resektion dieser Lasionen richten sich nach den aktuellen europaischen Leitlinien, deren Inhalte sind jedoch nicht evidenzbasiert, sondern stutzen sich auf Erkenntnisse und Empfehlungen von Experten. Gemas den Konsensusempfehlungen kann die asymptomatische seros-zystische Neoplasie (SCN) als serose Lasion mit niedriger Tendenz zur Entartung beobachtet werden. Im Gegensatz dazu sollten alle muzinos-zystischen Neoplasien (MCN) >4 cm sowie alle solid-pseudopapillaren Neoplasien (SPN) reseziert werden. Intraduktal papillar-muzinose Neoplasien (IPMNs), die aufgrund ihres Bezugs zum Pankreasgangsystem in Haupt(MD)- oder Seitengang(BD)-IPMNs unterteilt werden, sollten als MD-IPMN und als Mixed-type(MT)-IPMN reseziert werden. Das Entartungsrisiko der BD-IPMN ist variabler und abhangig von Risikofaktoren, die klinisch und bildmorphologisch definiert werden. Das therapeutische Management erfolgt daher individuell nach Risikoabschatzung. Um die Indikationsqualitat bei PCNs quantifizieren zu konnen und damit auch zu einer optimierten Versorgung beizutragen, werden dringend prospektive Langzeitstudien benotigt.

Bei den meisten Patienten mit einem Pankreaskarzinom kommt es im Verlauf zu einem Rezidiv, welches entweder lokal oder systemisch im Sinne von Leber- und/oder Lungenmetastasen auftritt. Durch die zunehmende Anwendung multimodaler Therapiekonzepte besteht ein Trend zu zunehmend radikalerer Chirurgie beim Pankreaskarzinom. Die Rolle der Chirurgie in der Rezidivsituation bleibt jedoch kontrovers. Die chirurgischen Optionen bei isoliertem Lokalrezidiv und bei einer metachronen Oligometastasierung beim Pankreaskarzinom werden dargestellt. Es erfolgte hierzu eine selektive Literaturrecherche und Zusammenfassung der derzeitigen Evidenz zur chirurgischen Behandlung. Fur die Metastasenchirurgie beim Pankreaskarzinom liegen aktuell keine randomisierten Studien vor. Die vorliegende Datenlage zeigt jedoch eindrucklich, dass insbesondere nach einer operativen Therapie bei Patienten mit einem Lokalrezidiv oder isoliert pulmonalen Metastasen mit geringer Morbiditat und Mortalitat ein Langzeituberleben von bis zu 32 bis 47 Monaten nach Metastasektomie erreicht werden kann. Auch bei einer Lebermetastasierung scheinen individuelle Therapiekonzepte, inklusive Resektionen nach systemtherapeutischer Vorbehandlung vielversprechend zu sein. Der groste Uberlebensvorteil zeigte sich hier ubereinstimmend fur alle Lokalisationen bei Patienten mit einem moglichst langen krankheitsfreien Intervall nach der Erstoperation. Die Behandlung eines isolierten Lokalrezidivs oder einer metachronen Oligometastasierung beim Pankreaskarzinom ist eine interdisziplinare Herausforderung und sollte an speziellen Pankreaszentren erfolgen. Eine chirurgische Resektion kann in Einzelfallen und eingebettet in ein multimodales Konzept sinnvoll sein.

Chronic pancreatitis (CP) is associated with alcohol abuse in 80% of cases. The primary treatment goals in CP are pain reduction and avoidance of pancreatitis-associated complications. CP should be treated in an interdisciplinary approach. A recent randomized clinical trial showed that early surgery compared with an endoscopy-first approach resulted in reduced pain levels. Surgical resections are, therefore, the most efficient treatment of pancreatitis-associated pain as well as other complications and should be performed early in the course of the disease. Since most of the patients pre­sent with chronic inflammation of the pancreatic head, pancreatic head resection is the most common treatment option. Duodenum-preserving pancreatic head resections are the surgical procedure of choice, but pancreaticoduodenectomies (Kausch-Whipple procedures) demonstrate similar outcome with regard to pain control, quality of life, and metabolic parameters. Other surgical procedures, including drainage procedures, pancreatic segmental resections, or left resections, are rarely indicated.

Objective To assess the perioperative and long-term outcome following pulmonary resection in patients with metachronous metastasis of pancreatic ductal adenocarcinoma (PDAC). Background Most patients with PDAC relapse or develop tumor spread to secondary organs. Currently, it remains unclear how to proceed with pulmonary metastasis in the metachronous setting. In particular, the role of surgery remains controversial. Methods Data of patients with pulmonary metachronous metastasis after PDAC collected from 2003 to 2015 in databases of two high-volume pancreatic cancer centers were retrospectively analyzed. Clinical and pathological aspects of primary PDAC as well as the perioperative and long-term outcome following pulmonary metastasectomy (PM) was evaluated, respectively. Patients with synchronous liver metastasis or metastasis to other secondary organs were excluded. Univariate survival analysis was performed. Results We identified 15 patients undergoing pulmonary resection for suspected metastasis after primary pancreatic resection. Operative and histopathologic evaluation revealed resectable pancreatic pulmonary metastasis in 11 patients (73.3%). The median disease-free survival (DFS) and overall survival (OS) after PM diagnosis was 18 months and 26 months, respectively. The median time to metachronous metastasis (TMM) was 17 months [3–64 months]. Perioperative morbidity was low with only one readmission (8.3%). There was no perioperative mortality. Patients who developed pulmonary metastasis later than 17 months after primary surgery showed better OS compared to those who did earlier (32.2 vs. 14.75 months, p = 0.025). In addition, patients with high-grade tumors had worse survival (12.4 vs. 31 months, p = 0.02). Elevated serum CEA levels or CA 19-9 levels were also not associated with shortened OS. Conclusions This study suggests that pulmonary metastasectomy after PDAC is safe and effective. Patients with extended DFS after primary pancreatic surgery as well as favorable tumor grading seem to particularly benefit from pulmonary surgery.

Originally described as an interferon (IFN)-γ-inducing factor, interleukin (IL)-18 has been reported to be involved in Th1 and Th2 immune responses, as well as in activation of NK cells and macrophages. There is convincing evidence that IL-18 plays an important role in various pathologies (i.e. inflammatory diseases, cancer, chronic obstructive pulmonary disease, Crohn's disease and others). Recently, IL-18 has also been shown to execute specific effects in pancreatic diseases, including acute and chronic pancreatitis, as well as pancreatic cancer. The aim of this study was to give a profound review of recent data on the role of IL-18 and its potential as a therapeutic target in pancreatic diseases. The existing data on this topic are in part controversial and will be discussed in detail. Future studies should aim to confirm and clarify the role of IL-18 in pancreatic diseases and unravel their molecular mechanisms.

Introduction Partial pancreatoduodenectomy (PD) is the treatment of choice for various benign and malignant tumours of the pancreatic head or the periampullary region. For reconstruction of the gastrointestinal passage, two stomach preserving PD variants exist: pylorus preservation (ppPD), or pylorus resection (prPD) with preservation of the stomach. In pancreatic surgery, delayed gastric emptying (DGE) remains a serious complication after PD with an incidence varying between 4.5% and 45%, potentially delaying hospital discharge or further treatment, e.g. adjuvant chemotherapy. Evidence is lacking to assess which variant of PD entails fewer postoperative DGE. Methods and analysis The protocol of a large-scale, multicentre, pragmatic, two-arm parallel-group, registry-based randomised controlled trial (rRCT) using a two-stage group-sequential design is presented. This patient-blind rRCT aims to demonstrate the superiority of prPD over ppPD with respect to the overall incidence of DGE within 30 days after index surgery in a German real-world setting. A total of 984 adults undergoing elective PD for any indication will be randomised in a 1:1 ratio. Patients will be recruited at about 30 hospitals being members of the StuDoQ|Pancreas registry established by the German Society of General and Visceral Surgery (DGAV). The postoperative follow-up for each patient will be 30 days. The primary analysis will follow an intention-to-treat approach and applies a binary logistic random intercepts model. Secondary perioperative outcomes include overall severe morbidity (Clavien-Dindo-classification), blood loss, 30-day all-cause mortality, postoperative hospital stay, and operation time. Complication rates and adverse events will be closely monitored. Ethics and dissemination This protocol was approved by the leading ethics committee of the Medical Faculty of the Ludwig-Maximilians-Universitat, Munich (reference no. 19-221). The results will be published in a peer-reviewed journal and presented at international conferences. Study findings will also be disseminated via the website (http://www.dgav.de/studoq/pylorespres/). Trial registration number DRKS-ID: DRKS00018842 (https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00018842, prospectively registered on 24-Oct-2019) ARTICLE SUMMARY Strengths and limitations of this study ▪This will be the first large-scale, surgical registry-based randomised controlled trial (rRCT) in Germany. ▪Patients will be blinded to the allocated and actually performed treatment. ▪The active control intervention will be pylorus preserving pancreatoduodenectomy (PD), currently the surgical standard treatment of tumours of the pancreatic head and periampullary region. ▪Synthesizing evidences from RCTs for this comparative effectiveness research question (preserving vs. resecting PD) is inconclusive with respect to delayed gastric emptying (DGE), a common post-operative complication. ▪The rRCT approach combines the advantages of a prospective (adaptive two-stage) 2-arm parallel-group RCT and the German multicentre StuDoQ|Pancreas registry as platform for patient enrolment, allocation and data collection, with the aim of improving the evidence-based surgical techniques for PD.

The cardinal symptom of chronic pancreatitis is severe belt-like upper abdominal pain, which requires immediate and adequate treatment. Furthermore, advanced stage chronic pancreatitis is often associated with complications, such as pancreatic pseudocysts, pancreatic duct stones and stenosis as well as biliary stenosis. The various endoscopic and surgical treatment options for chronic pancreatitis patients have been controversially discussed for decades. The new German S3 guidelines on pancreatitis now clearly define the best treatment options depending on the indications for treatment. For the treatment of pain in chronic pancreatitis it has been known for a long time that a surgical intervention is superior to endoscopic intervention concerning long-term pain relief. The recently published ESCAPE study has further underlined this by showing that early surgical intervention was superior to a step-up approach with initial endoscopic treatment. For the treatment of pancreatic pain, an initial endoscopic treatment attempt is therefore justified for short-term pain relief but in the midterm and long term, surgical intervention is the treatment of choice. In contrast, pancreatic pseudocysts, solitary proximally situated pancreatic duct stones and benign biliary strictures (except in calcifying pancreatitis) can nowadays generally be managed endoscopically. For distal pancreatic duct stones and symptomatic pancreatic duct stenosis surgical treatment is again the method of choice. This review article discusses these indication-related procedures in detail and explains them in relation to the recently published S3 guidelines on pancreatitis of the German Society for Gastroenterology, Digestive and Metabolic Diseases (DGVS).Das Kardinalsymptom der chronischen Pankreatitis ist ein sehr heftiger, gürtelförmiger Oberbauchschmerz, der einer zeitnahen und suffizienten Behandlung bedarf. Darüber hinaus kommt es bei der chronischen Pankreatitis häufig zu Folgekomplikationen wie Pankreaspseudozysten, Pankreasgangsteinen und -stenosen sowie Gallenwegstenosen. Während über den Stellenwert von endoskopischen vs. chirurgischen Behandlungsverfahren sehr lange kontrovers diskutiert wurde, richten sich die Behandlungsverfahren der Wahl heute nach der Indikation und sind in der neuen S3-Leitlinie zur Pankreatitis klar formuliert. Es ist schon lange bekannt, dass chirurgische Verfahren den endoskopischen in der Therapie von Schmerzen bei chronischer Pankreatitis überlegen sind. Dies wurde durch die erst kürzlich publizierte ESCAPE-Studie noch unterstrichen, in der eine frühe chirurgische Intervention einem „step-up approach“ mit initialer Endoskopie überlegen war. Somit ist zur kurzfristigen Schmerztherapie ein endoskopischer Therapieversuch zwar gerechtfertigt, mittel- und langfristig sollte jedoch ein operatives Verfahren zur Anwendung kommen. Im Gegensatz dazu können Pankreaspseudozysten, einzelne proximal gelegene Pankreasgangsteine sowie benigne Gallengangstenosen (außer bei kalzifizierender Pankreatitis) heute in der Regel endoskopisch gut beherrscht werden. Bei distal gelegenen Pankreasgangsteinen sowie symptomatischen Pankreasgangstenosen ist wiederum die chirurgische Therapie das Verfahren der Wahl. Der vorliegende Übersichtsbeitrag diskutiert diese indikationsbezogenen Verfahren im Detail und erörtert sie in enger Anlehnung an die kürzlich veröffentlichte neue S3-Leitlinie „Pankreatitis“ der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS).

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.

Das duktale Adenokarzinom des Pankreas (PDAC), haufig unscharf als Pankreaskarzinom bezeichnet, stellt mit Abstand die haufigste histopathologische Entitat maligner Raumforderungen des Pankreas dar. Im folgenden Beitrag werden Atiologie, Pathogenes und Genetik des PDAC erlautert. Des Weiteren werden diagnostische Masnahmen sowie Therapiemoglichkeiten und -ziele dargestellt.

Die Behandlung des Pankreaskarzinoms hat in den letzten Jahren deutliche Fortschritte gemacht. In Kombination mit einer (neo)adjuvanten Chemotherapie ist die chirurgische Resektion der einzige kurative Therapieansatz. Aktuelle Standards und moglicher Perspektiven in der Chirurgie des Pankreaskarzinoms sollen dargestellt werden. Es erfolgten eine selektive Literaturrecherche und Zusammenfassung der derzeitigen Evidenz zur chirurgischen Behandlung lokaler und lokal fortgeschrittener Pankreaskarzinome. Die chirurgische Therapie des primar resektablen Pankreaskarzinoms ist heute in spezialisierten Zentren hochgradig standardisiert. Bei Borderline-resektablen Pankreaskarzinomen, bei denen primar sicher keine R0-Resektion erreicht werden kann, wird durch Einsatz einer neoadjuvanten Chemotherapie eine sekundare Resektabilitat angestrebt. Beim primar irresektablen, lokal fortgeschrittenen Pankreaskarzinom stehen sequenzielle Therapiekonzepte, die systemische Therapie, Strahlentherapie und Chirurgie beinhalten, im Vordergrund. Primare und sekundare Resektionen sind heute in entsprechenden Zentren sehr sicher mit einer geringen Morbiditat und Mortalitat durchfuhrbar. Die Behandlung von insbesondere Borderline-resektabler und lokal fortgeschrittener Pankreaskarzinome ist eine interdisziplinare Herausforderung und sollte an speziellen Pankreaszentren erfolgen.

With an increasing number of hospital admissions, an average of 16-to 20 days in hospital per year, 34% of patients constantly taking pain medication, 57% in need of enzyme supplementation, and 29% with diabetes mellitus, chronic pancreatitis is a debilitating disease of high socio-economic relevance. In total, 33% of all patients suffering from chronic pancreatitis can no longer practice their original profession. The number of unemployed chronic pancreatitis patients due to prolonged stays in hospital or continued alcohol abuse is known to be as high as 40%. Continued alcohol abuse with a hazard ratio (HR) of 1.6, smoking with a HR of 1.4, and the presence of liver cirrhosis with a HR of 2.5 negatively affects the prognosis of chronic pancreatitis. In a patient cohort burdened with high co-morbidity, endoscopic therapy can provide short-term relief of symptoms. Endotherapy is the first line of management in chronic pancreatitis with symptomatic pancreatobiliary ductal obstruction. Further studies are required in certain key areas such as the use of fully covered self-expanding metallic stents for pancreatic ductal and biliary strictures. Long-term success rates can mainly be achieved by surgical procedures, which can be performed with acceptable morbidity in pancreatic centers. The current review focuses on the advantages and disadvantages of endoscopic and surgical treatment of chronic pancreatitis.

Background & Aims Oncogenic KrasG12D induces neoplastic transformation of pancreatic acinar cells through acinar-to-ductal metaplasia (ADM), an actin-based morphogenetic process, and drives pancreatic ductal adenocarcinoma (PDAC). mTOR (mechanistic target of rapamycin kinase) complex 1 (mTORC1) and 2 (mTORC2) contain Rptor and Rictor, respectively, and are activated downstream of KrasG12D, thereby contributing to PDAC. Yet, whether and how mTORC1 and mTORC2 impact on ADM and the identity of the actin nucleator(s) mediating such actin rearrangements remain unknown. Methods A mouse model of inflammation-accelerated KrasG12D-driven early pancreatic carcinogenesis was used. Rptor, Rictor, and Arpc4 (actin-related protein 2/3 complex subunit 4) were conditionally ablated in acinar cells to deactivate the function of mTORC1, mTORC2 and the actin-related protein (Arp) 2/3 complex, respectively. Results We found that mTORC1 and mTORC2 are markedly activated in human and mouse ADM lesions, and cooperate to promote KrasG12D-driven ADM in mice and in vitro. They use the Arp2/3 complex as a common downstream effector to induce the remodeling the actin cytoskeleton leading to ADM. In particular, mTORC1 regulates the translation of Rac1 (Rac family small GTPase 1) and the Arp2/3-complex subunit Arp3, whereas mTORC2 activates the Arp2/3 complex by promoting Akt/Rac1 signaling. Consistently, genetic ablation of the Arp2/3 complex prevents KrasG12D-driven ADM in vivo. In acinar cells, the Arp2/3 complex and its actin-nucleation activity mediated the formation of a basolateral actin cortex, which is indispensable for ADM and pre-neoplastic transformation. Conclusions Here, we show that mTORC1 and mTORC2 attain a dual, yet nonredundant regulatory role in ADM and early pancreatic carcinogenesis by promoting Arp2/3 complex function. The role of Arp2/3 complex as a common effector of mTORC1 and mTORC2 fills the gap between oncogenic signals and actin dynamics underlying PDAC initiation.

Background An increasing body of evidence suggests that microbiota may promote progression of pancreatic ductal adenocarcinoma (PDAC). It was hypothesized that gammaproteobacteria (such as Klebsiella pneumoniae) influence survival in PDAC, and that quinolone treatment may attenuate this effect. Methods This was a retrospective study of patients from the Massachusetts General Hospital (USA) and Ludwig-Maximilians-University (Germany) who underwent preoperative treatment and pancreatoduodenectomy for locally advanced or borderline resectable PDAC between January 2007 and December 2017, and for whom a bile culture was available. Associations between tumour characteristics, survival data, antibiotic use and results of intraoperative bile cultures were investigated. Survival was analysed using Kaplan-Meier curves and Cox regression analysis. Results Analysis of a total of 211 patients revealed that an increasing number of pathogen species found in intraoperative bile cultures was associated with a decrease in progression-free survival (PFS) (-1·9 (95 per cent c.i. -3·3 to -0·5) months per species; P = 0·009). Adjuvant treatment with gemcitabine improved PFS in patients who were negative for K. pneumoniae (26·2 versus 15·3 months; P = 0·039), but not in those who tested positive (19·5 versus 13·2 months; P = 0·137). Quinolone treatment was associated with improved median overall survival (OS) independent of K. pneumoniae status (48·8 versus 26·2 months; P = 0·006) and among those who tested positive for K. pneumoniae (median not reached versus 18·8 months; P = 0·028). Patients with quinolone-resistant K. pneumoniae had shorter PFS than those with quinolone-sensitive K. pneumoniae (9·1 versus 18·8 months; P = 0·001). Conclusion K. pneumoniae may promote chemoresistance to adjuvant gemcitabine, and quinolone treatment is associated with improved survival.

Oncogenic KrasA mouse model of inflammation-accelerated KrasWe found that mTORC1 and mTORC2 are markedly activated in human and mouse ADM lesions, and cooperate to promote KrasHere, we show that mTORC1 and mTORC2 attain a dual, yet nonredundant regulatory role in ADM and early pancreatic carcinogenesis by promoting Arp2/3 complex function. The role of Arp2/3 complex as a common effector of mTORC1 and mTORC2 fills the gap between oncogenic signals and actin dynamics underlying PDAC initiation.

Introduction The number of people aged 60 and above will rise from 46 million in 2015 to 157 in 2050 million, exceeding 30% of the population in many western countries. Consequently, the demand for oncological therapy for elderly patients will increase within the next decades. Currently, sufficient data on neoadjuvant therapy (NTx) of pancreatic cancer in elderly patients are lacking. Methods Data of a multinational, retrospective database were screened for patients having received preoperative FOLFIRINOX (FFx) or Gemcitabine/nab-paclitaxel (GNP) for locally advanced and borderline resectable pancreatic cancer (LAPC/BRPC) before June 2017. Data were included in an intention-to-treat-analysis and outcomes were compared between non-aged and elderly patients using a cut-off age of 63 (comparison 1) and 70 years (comparison 2). Results Of 165 patients receiving NTx, 76 and 33 were older than 63 and 70 years. Baseline characteristics revealed that elderly patients preferably undergo GNP (comparison 1: p = 0.063; comparison2: p = 0.005), with less cycles of NTx (comparison 1: p = 0.057). Whereas reductions of NTx dosage was more common in elderly patients in comparison 1 (p = 0.003), resection rates (p = 0.575; p = 1.000) and median survival (p = 0.406; p = 0.499) were not different. Whereas resected patients showed no differences in survival (p = 0.328; p = 0.132), patients aged >70 years showed a decreased progression-free survival (p = 0.019). Conclusion Elderly patients treated with NTx show encouragingly high resection rates. If comorbidities allow for FFx or GNP, elderly patients with LAPC/BRPC can offered NTx with the prospect of survival comparable to younger patients.

While comprehensive scientific efforts to understand the biology of pancreatic ductal adenocarcinoma (PDAC) have been significantly expedited, this knowledge has—as of yet—not translated into a clinical benefit, especially for unresectable patients. Moreover, advances of long-term outcomes for those patients lag behind compared to improvements in the treatment of many other malignancies over the past few decades. For patients with PDAC, cytotoxic chemotherapy remains the backbone of systemic treatment. In general, for patients with resectable disease and otherwise acceptable state of health, modified 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin (mFOLFIRINOX) is the standard-of-care adjuvant therapy; also, recent prospective data have suggested its usefulness as neoadjuvant treatment strategies in locally advanced and borderline resectable patients. Several randomized controlled trials addressing this question are currently recruiting. In comparison, for patients with advanced-stage or metastatic disease options remain mostly limited to palliative chemotherapy. Thus, novel therapeutic approaches are desperately needed. In this regard, comprehensive genomic profiling in the wake of personalized medicine has revealed several potentially actionable alterations with reasonable feasibility to implement such strategies, but the subsets of patients benefiting from those approaches remain small so far. Among the groups with significant benefit are PDAC patients most notably with BRCA1/2 mutations, mismatch repair deficiencies, or NTRK1-3 fusions. An increasing number of publications together with a growing array of clinical trials are trying to shed light on the field with the idea of repurposing established drugs for antineoplastic use in PDAC therapy. As such, recycling drugs could present an intriguing and fast-track method with new therapeutic paradigms in anticancer treatment. In this chapter, we aim to summarize important aspects of repurposing drugs for PDAC therapy in past and present together with available data on novel findings and potential future directions of this emerging field.

Chronic pancreatitis is a fibroinflammatory syndrome of the exocrine pancreas, which is characterized by an increasing incidence, high morbidity and lethality. Common etiologies besides alcohol and nicotine consumption include genetic causes and risk factors. The life time risk for the development of pancreatic cancer is elevated 13- to 45-fold depending on the underlying etiology. In patients with chronic pancreatitis clinical, laboratory and imaging surveillance for early detection of complications, including pancreatic cancer, is recommended, although the available methods lack the desired sensitivity and specificity. In this article we review the epidemiology, etiologies and risk factors for chronic pancreatitis and pancreatic cancer and discuss current recommendations for screening and management of patients at risk for tumor development.

Temporary intra-operative portocaval shunts (TPCS) are believed to improve outcomes after cava-sparing liver transplantation. We hypothesize that decompression of the portal venous system via a TPCS reduces gut congestion, thereby decreasing bacterial translocation. Thus, we sought to clarify whether transplantation with a TPCS alters rates of post-operative infections and survival.Patients undergoing liver transplantation (n = 189) were stratified by usage of a TPCS and the type of intra-operative antibiotic prophylaxis. Rates of post-operative infections were analyzed using the χThe analysis of patients transplanted with a TPCS and meropenem revealed increased infection rates with gut-specific pathogens (Escherichia coli, Escherichia faecalis, Escherichia faecium; p = 0.04) and equal 120-d survival in comparison with patients transplanted without a TPCS. When vancomycin was added to meropenem infection rates did not differ and patients transplanted with a TPCS had better survival in comparison with patients transplanted without a TPCS (p = 0.02). Within the TPCS group, the administration of meropenem and vancomycin was associated with improved survival in comparison with meropenem only (p = 0.03).Survival of patients may be improved by usage of a TPCS when gut-specific pathogens are covered by intra-operative antibiotic prophylaxis.

Paragangliomas are predominantly benign tumors, but in some cases invasive growth and also metastasis are observed. Given the limited number of nonsurgical treatment options, novel target structures for diagnostics and therapy of this tumor entity are urgently needed. In the present study, expression of all five somatostatin receptor (SST) subtypes, chemokine receptor CXCR4 and endothelin receptor type A (ETA) was assessed by means of immunohistochemistry in a total of 66 paraffin-embedded paraganglioma samples from 55 patients. The stainings were rated by means of the Immunoreactive Score and correlated to clinical data and to succinate dehydrogenase subunit B (SDHB) expression. SST2A was by far the most prominent receptor in the paragangliomas investigated. It was present in 89% of the tumors at a high intensity, followed by SST5, SST3, SST1 and SST4, which were detected in 47%, 35%, 35% and 13% of the samples, respectively. SDHB positive tumors exhibited significantly higher SST2A and SST3 expression as compared to SDHB negative cases. There was no correlation between SST and Ki-67 expression or grading of the tumors and no difference in SST expression between primary tumors and metastases. Cell surface expression of CXCR4 and ETA was detected only in few samples. On tumor capillaries, however, exceptionally strong staining for these two receptors was noticed in the vast majority of the tumors. In conclusion, paragangliomas are well suited for SST2A-based diagnostics and treatment modalities. An indirect targeting of these highly vascularized tumors via CXCR4 or ETA may also represent a promising future strategy.

Multimodale Therapiekonzepte haben dazu beigetragen, die Prognose von Patienten mit Osophagustumoren zu verbessern. Das gilt fur Adeno- wie auch fur Plattenepithelkarzinome. Kritisch fur eine adaquate Therapie ist eine enge interdisziplinare Zusammenarbeit aller Beteiligten, ohne die sich aktuelle diagnostische und therapeutische Konzepte nicht umsetzen lassen.

A prolonged time to treatment initiation (TTI) correlates with an adverse prognosis in different cancer types including resectable pancreatic cancer (PC). Only limited evidence on the correlation between TTI and prognosis in advanced PC exists. Consecutive PC patients (n = 368) who were diagnosed or treated at our high-volume comprehensive cancer center were included in a prospectively maintained database. We retrospectively analyzed time from first imaging showing advanced PC to initiation of palliative first-line chemotherapy. Lead time bias and waiting time paradox were addressed by landmark analysis and correlation of tumor burden with TTI. Two hundred and ninety-seven patients met the pre-specified in- and exclusion criteria of our study. Median TTI was 29 days (range: 1–124 days). Most common reasons for prolonged TTI (> 21 days) were referral from an external treatment center (39%) and a second biopsy (31%). A TTI above the median-, 75th or 90th percentile (43 or 60 days, respectively) had no impact on overall survival. Furthermore, no correlation between levels of carbohydrate antigen 19-9 (CA 19-9) at time of treatment initiation and TTI was observed. While a timely work-up of advanced PC patients remains important, delays in treatment initiation due to repeated biopsies, inclusion in a clinical study or transfer to a specialized cancer center appear to be justified in light of the absence of a strong adverse effect of prolonged TTI on prognosis in advanced PC patients.

Background Cathepsin-D (CatD), owing to its dual role as a proteolytic enzyme and as a ligand, has been implicated in cancer progression. The role of CatD in pancreatic ductal adenocarcinoma is unknown. Methods CatD expression quantified by immunohistochemistry of tumor-tissue microarrays of 403 resected pancreatic cancer patients from the ESPAC-Tplus trial, a translational study within the ESPAC (European Study Group for Pancreatic Cancer) trials, was dichotomously distributed to low and high H scores (cut off 22.35) for survival and multivariable analysis. The validation cohort (n = 69) was recruited based on the hazard ratio of CatD from ESPAC-Tplus. 5-fluorouracil-, and gemcitabine-resistant pancreatic cancer cell lines were employed for mechanistic experiments. All statistical tests were two-sided. Results Median overall survival was 23.75 months and median overall survival for patients with high CatD expression was 21.09 (95% confidence interval [CI] = 17.31 to 24.80) months vs 27.20 (95% CI = 23.75 to 31.90) months for low CatD expression (χ2LR, 1DF = 4.00; P = .04). Multivariable analysis revealed CatD expression as a predictive marker in gemcitabine-treated (z stat = 2.33; P = .02) but not in 5-fluorouracil-treated (z stat = 0.21; P = .82) patients. An independent validation cohort confirmed CatD as a negative predictive marker for survival (χ2LR, 1DF = 6.80; P = .009) and as an independent predictive marker in gemcitabine-treated patients with a hazard ratio of 3.38 (95% CI = 1.36 to 8.38, P = .008). Overexpression of CatD was associated with a concomitant suppression of the acid sphingomyelinase, and silencing of CatD resulted in upregulation of acid sphingomyelinase with rescue of gemcitabine resistance. Conclusions Adjuvant gemcitabine is less effective in pancreatic ductal adenocarcinoma with high CatD expression, and thus CatD could serve as a marker for biomarker-driven therapy.

Immunotherapy has become an established pillar of cancer treatment improving the prognosis of many patients with a broad variety of hematological and solid malignancies. The two main drivers behind this success are checkpoint inhibitors (CPIs) and chimeric antigen receptor (CAR) T cells. This review summarizes seminal findings from clinical and translational studies recently presented or published at important meetings or in top-tier journals, respectively. For checkpoint blockade, current studies focus on combinational approaches, perioperative use, new tumor entities, response prediction, toxicity management and use in special patient populations. Regarding cellular immunotherapy, recent studies confirmed safety and efficacy of CAR T cells in larger cohorts of patients with acute lymphoblastic leukemia or diffuse large B cell lymphoma. Different strategies to translate the striking success of CAR T cells in B cell malignancies to other hematological and solid cancer types are currently under clinical investigation. Regarding the regional distribution of registered clinical immunotherapy trials a shift from PD-1 / PD-L1 trials (mainly performed in the US and Europe) to CAR T cell trials (majority of trials performed in the US and China) can be noted.

Acute pancreatitis is a common disease characterized by acinar cell destruction and acute inflammatory changes of the pancreas that lead to a systemic inflammatory response. A major research effort has been undertaken to unravel the underlying pathophysiology and to identify possible therapeutic targets. Still, only very few findings have influenced our clinical practice in the treatment of acute pancreatitis. Pancreatic microcirculation and capillary blood flow have long been suspected to play a major role in the course of the disease. It therefore seemed tempting to speculate that manipulation of the vasoconstrictor endothelin or its antagonist nitrogen monoxide could positively influence the outcome. We had to acknowledge, however, that these mechanisms take place very early in the disease course and that only prophylactic applications show an effect; this is useful in the setting of pancreas transplantation and endoscopic retrograde cholangiopancreatography but not applicable for clinical use in the therapy of acute pancreatitis. Research then focused on later pathophysiological stages of the disease, mainly on the process of adhesion and extravasation of leukocytes into the pancreatic tissue. Here, integrins and adhesion molecules like the intercellular adhesion molecule-1 (ICAM-1) were investigated in detail. A monoclonal antibody to ICAM-1 showed promising results in experimental models but was never further evaluated in the clinical setting. Hemodilution and fluid resuscitation was recognized to be an important therapeutic tool in acute pancreatitis. Here, initial experimental studies favored colloid solutions, and especially dextrans for isovolemic fluid resuscitation. It was recognized only later that colloid solutions are not effective and may even increase mortality in critically ill patients. Therefore, goal-directed infusion of Ringer's lactate solution at a moderate infusion rate to optimize volume status and hemoconcentration in acute pancreatitis is now advocated. In summary, out of the numerous experimental and translational studies, only very few have really influenced our daily clinical practice. Further research is therefore needed to find more specific and effective therapeutic agents for the treatment of acute pancreatitis.