Current studies pictured the enteric nervous system and macrophages as modulators of neuroimmune processes in the inflamed gut. Expanding this view, we investigated the impact of enteric neuron-macrophage interactions on postoperative trauma and subsequent motility disturbances, i.e., postoperative ileus. In the early postsurgical phase, we detected strong neuronal activation, followed by transcriptional and translational signatures indicating neuronal death and synaptic damage. Simultaneously, our study revealed neurodegenerative profiles in macrophage-specific transcriptomes after postoperative trauma. Validating the role of resident and monocyte-derived macrophages, we depleted macrophages by CSF-1R-antibodies and used CCR2-/- mice, known for reduced monocyte infiltration, in POI studies. Only CSF-1R-antibody-treated animals showed decreased neuronal death and lessened synaptic decay, emphasizing the significance of resident macrophages. In human gut samples taken early and late during abdominal surgery, we substantiated the mouse model data and found reactive and apoptotic neurons and dysregulation in synaptic genes, indicating a species' overarching mechanism. Our study demonstrates that surgical trauma activates enteric neurons and induces neurodegeneration, mediated by resident macrophages, introducing neuroprotection as an option for faster recovery after surgery.

Background and Aim:There are several existing systemic 1st- line therapies for advanced hepatocellular carcinoma (HCC), including atezolizumab/bevacizumab (Atez/Bev), sorafenib and lenvatinib. This study aims to compare the effectiveness of these three 1st-line systemic treatments in a real-world setting for HCC, focusing on specific patient subgroups analysis.Methods:A total of 177 patients with advanced HCC treated with Atez/Bev (n = 38), lenvatinib (n = 21) or sorafenib (n = 118) as 1st line systemic therapy were retrospectively analyzed and compared. Primary endpoints included objective response rate (ORR), progression-free survival (PFS) and 15-month overall survival (15-mo OS). Subgroups regarding liver function, etiology, previous therapy and toxicity were analyzed.Results:Atez/Bev demonstrated significantly longer median 15-month OS with 15.03 months compared to sorafenib with 9.43 months (p = 0.04) and lenvatinib with 8.93 months (p = 0.05). Similarly, it had highest ORR of 31.6% and longest median PFS with 7.97 months, independent of etiology. However, significantly superiority was observed only compared to sorafenib (ORR: 4.2% (p < 0.001); PFS: 4.57 months (p = 0.03)), but not comparing to lenvatinib (ORR: 28.6% (p = 0.87); PFS: 3.77 months (p = 0.10)). Atez/Bev also resulted in the longest PFS in patients with Child-Pugh A and ALBI 1 score and interestingly in those previously treated with SIRT. Contrary, sorafenib was non inferior in patients with impaired liver function.Conclusion:Atez/Bev achieved longest median PFS and 15-mo OS independent of etiology and particularly in patients with stable liver function or prior SIRT treatment. Regarding therapy response lenvatinib was non-inferior to Atez/Bev. Finally, sorafenib seemed to perform best for patients with deteriorated liver function.

Objective Splenectomy is regularly performed in total and distal pancreatectomy due to technical reasons, lymph node dissection and radicality of the operation. However, the spleen serves as an important organ for competent immune function, and its removal is associated with an increased incidence of cancer and a worse outcome in some cancer entities1–3. The impact of splenectomy in pancreatic cancer is not fully resolved4,5. Methods We therefore compared the outcome of 193 pancreatic cancer patients who underwent total or distal pancreatectomy with (Sp) or without splenectomy (NoSp) between 2015 and 2021 using the StuDoQ|Pancreas registry of the German Society for General and Visceral Surgery. In addition, we integrated our data into the existing literature in a meta-analysis of studies on splenectomy in pancreatic cancer patients. Results There was no difference between the Sp and NoSp groups regarding histopathological parameters, number of examined or affected lymph nodes, or residual tumor status. We observed a significantly prolonged survival in pancreatic cancer patients who underwent total pancreatectomy, when a spleen-preserving operation was performed (median survival: 9.6 vs. 17.3 months, p = 0.03). In this group, splenectomy was identified as an independent risk factor for shorter overall survival [HR (95%CI): 2.4 (1.18–4.9)]. In a meta-analysis of the existing literature in combination with our data, we confirmed splenectomy as a risk factor for a shorter overall survival in pancreatic cancer patients undergoing total pancreatectomy, distal pancreatectomy, or pancreatic head resection [HR (95%CI): 1.53 (1.11–1.95)]. Conclusion Whenever technically possible, preservation of the spleen should be considered during total pancreatectomy for resection of pancreatic cancer, as the spleen seems to affect the long-term survival in this subgroup. The immunological reasons behind this observation deserve further investigation.

Background: Pancreatic adenocarcinoma (PaC) still has a dismal prognosis, and despite medical advances, a bleak 5-year survival rate of only 8%, largely due to late diagnosis and limited curative surgical options for most patients. Frontline palliative treatment shows some survival advantages. However, the high disease mortality is accompanied by high morbidity including cancer-related pain and additional symptoms, which strongly impair patients’ quality of life (QOL). At present, there is no established strategy for local therapy for PaC primarily aiming to manage local tumor growth and alleviate associated symptoms, particularly pain. In recent years, non-invasive high-intensity focused ultrasound (HIFU) has shown promising results in reducing cancer pain and tumor mass, improving patients’ QOL with few side effects. Study design: This is the first randomized controlled trial worldwide including 40 patients with inoperable pancreatic adenocarcinoma randomized into two groups: group A undergoing standard chemotherapy; and group B undergoing standard chemotherapy plus local HIFU treatment. This study aims to establish a robust evidence base by examining the feasibility, safety, and efficacy of US-guided HIFU in combination with standard palliative systemic therapy for unresectable PaC. Primary endpoint assessments will focus on parameters including safety issues (phase I), and local response rates (phase II).

Einleitung Das extrahepatische Cholangiokarzinom (eCCA) ist noch immer ein Malignom mit schlechter Prognose. Die leitliniengerechte palliative Therapie besteht aus endobiliärem Stenting und systemischer Chemotherapie (SC). Endobiliäre tumorablative Techniken wie photodynamischer Therapie (ePDT) und Radiofrequenzablation (eRFA) haben bereits gute Verträglichkeit und positive Effekte auf das Patientenüberleben gezeigt.

TPS4193 Background: As of today, the recommendation for patients with adenocarcinoma of the pancreas and hepatic metastases is systemic chemotherapy alone regardless of the number and location of metastases. In the past, case reports have repeatedly reported survival data of patients who received metastatic and primary tumor resection outside the guidelines. However, there are currently no controlled clinical data from prospective studies that have evaluated the effectiveness of systemic chemotherapy in combination with tumor and metastasis resection in the context of hepatic oligometastasis in pancreatic cancer. Methods: In this single arm, phase-2 trial, survival data from patients receiving neoadjuvant chemotherapy followed by R0/R1 resection will be compared to historic data from patients with oligometastatic adenocarcinoma of the pancreas. Inclusion criteria are patients with a maximum of 5 liver metastases and histology proven PDAC. The combination of liposomal irinotecan (nal-IRI), oxaliplatin (OX) and 5-fluouracil (5-FU)/folinic acid (FA) (Nal-IRIFOX) was chosen as neoadjuvant chemotherapy since recent data suggested superior efficacy and less toxicity compared to mFOLFIRINOX. The primary endpoint is overall survival (OS) after R0/R1 resection. Secondary efficacy endpoints are R0/R1 resection rate and progression-free survival (PFS). Secondary safety endpoints are type, frequency and severity of adverse events with severity according to NCI CTCAE version 5.0 and perioperative morbidity and mortality. Eligible patients with hepatic oligometastatic adenocarcinoma of the pancreas will receive neoadjuvant combination chemotherapy in cycles of 14 days for a duration of 16 weeks in total. In patients with progressive disease during or after the first 4 cycles, neoadjuvant chemotherapy will be permanently discontinued. Patients with tumor response or stable disease after the first 4 cycles according to RECIST v1.1 but a non-resectable primary tumor will receive 4 more cycles. Patients with tumor response or stable disease and a resectable primary tumor after the first 4 cycles will undergo explorative laparotomy and synchronous resection of the tumor and hepatic metastases, if feasible. In total 150 patients will be enrolled for this trial with an aim of 55 patients receiving a complete macroscopic synchronous tumor and metastatic resection. The study is currently ongoing on 11 high-volume centers for pancreatic surgery within Germany. This is the first clinical study to prospectively evaluate the value of multimodality therapy concepts in oligometastatic pancreatic cancer. Clinical trial information: NCT04617457 .

ZusammenfassungHintergrundRobotergestutzten Rektumresektionen wird nachgesagt, dass sie bekannte Schwierigkeiten der laparoskopischen Rektumchirurgie durch technische Vorteile uberwinden und so zu besseren Behandlungsergebnissen fuhren. Veroffentlichte Studien berichten jedoch sehr heterogene Ergebnisse. Ziel dieser Arbeit ist es daher, festzustellen, ob es eine Klasse-1a-Evidenz fur den Vergleich von robotergestutzten vs. laparoskopischen Rektumresektionen gibt. Weiterhin mochten wir die Behandlungsergebnisse unserer Klinik mit den berechneten Effekten aus der Literatur vergleichen.Material und MethodenEine systematische Literaturrecherche nach Klasse-1a-Evidenz wurde durchgefuhrt und die berechneten Effekte fur 7 vorausgewahlte Endpunkte wurden miteinander verglichen. Anschlie ss end analysierten wir alle elektiven Rektumresektionen, die zwischen 2017 und 2020 in unserer Klinik durchgefuhrt wurden, und verglichen die Behandlungsergebnisse mit den Ergebnissen der identifizierten Metaanalysen.ErgebnisseDie Ergebnisse der 7 identifizierten Metaanalysen zeigten keine homogenen Effekte fur die Endpunkte Operationszeit und Konversionsrate, wahrend die berechneten Effekte der anderen untersuchten Endpunkte weitgehend konsistent waren. Unsere Patientendaten zeigten, dass robotergestutzte Rektumresektionen mit signifikant langeren Operationszeiten assoziiert waren, wahrend die anderen Outcomes kaum von der Operationstechnik beeinflusst wurden.DiskussionObwohl bereits Klasse-1a-Metaanalysen zum Vergleich von robotergestutzten und laparoskopischen Rektumresektionen vorliegen, erlauben diese keine evidenzbasierte Empfehlung zur Bevorzugung einer der beiden Operationstechniken. Die Analyse unserer Patientendaten zeigte, dass die in unserer Klinik erzielten Ergebnisse weitgehend mit den beobachteten Effekten der Metaanalysen ubereinstimmen. AbstractBackgroundRobot-assisted rectal resections are said to overcome the known difficulties of laparoscopic rectal surgery through technical advantages, leading to better treatment results; however, published studies reported very heterogeneous results. The aim of this paper is therefore to determine whether there is class 1a evidence comparing robotic versus laparoscopic rectal resections. Furthermore, we would like to compare the treatment results of our clinic with the calculated effects from the literature.Material and methodsA systematic literature search for class 1a evidence was performed and the calculated effects for 7 preselected outcomes were compared. We then analyzed all elective rectal resections performed in our hospital between 2017 and 2020 and compared the treatment outcomes with the results of the identified meta-analyses.ResultsThe results of the 7 identified meta-analyses did not show homogeneous effects for the outcomes operating time and conversion rate, while the calculated effects of the other outcomes studied were largely consistent. Our patient data showed that robotic rectal resections were associated with significantly longer operation times, while the other outcomes were hardly influenced by the surgical technique.DiscussionAlthough class 1a meta-analyses comparing robotic and laparoscopic rectal resections already exist, they do not enable an evidence-based recommendation regarding the preference of one of the two surgical techniques. The analysis of our patient data showed that the results achieved in our clinic are largely consistent with the observed effects of the meta-analyses.

Background and Aims: Human innate lymphoid cells (ILCs) are critically involved in the modulation of homeostatic and inflammatory processes in various tissues. However, only little is known about the composition of the intrahepatic ILC pool and its potential role in chronic liver disease. Here, we performed a detailed characterization of intrahepatic ILCs in both healthy and fibrotic livers.Approach and Results: A total of 50 livers (nonfibrotic = 22, and fibrotic = 29) were analyzed and compared with colon and tonsil tissue (each N = 14) and peripheral blood (N = 32). Human intrahepatic ILCs were characterized ex vivo and on stimulation using flow cytometry and single-cell RNA sequencing. ILC differentiation and plasticity were analyzed by both bulk and clonal expansion experiments. Finally, the effects of ILC-derived cytokines on primary human HSteCs were studied. Unexpectedly, we found that an "unconventional" ILC3like cell represented the major IL-13-producing liver ILC subset. IL-13(+) ILC3-like cells were specifically enriched in the human liver, and increased frequencies of this cell type were found in fibrotic livers. ILC3-derived IL-13 production induced upregulation of proinflammatory genes in HSteCs, indicating a potential role in the regulation of hepatic fibrogenesis. Finally, we identified KLRG1expressing ILC precursors as the potential progenitor of hepatic IL-13(+) ILC3like cells.Conclusions: We identified a formerly undescribed subset of IL-13-producing ILC3-like cells that is enriched in the human liver and may be involved in the modulation of chronic liver disease.

(1) Background: This study’s goals were to investigate possible risk factors for clinically relevant postoperative pancreatic fistula (POPF) grade B/C according to the updated definitions of the International Study Group of Pancreatic Surgery and to analyze possible treatment strategies; (2) Methods: Between 2017 and 2021, 200 patients were analyzed regarding the development of POPF grade B/C with an emphasis on postoperative outcome and treatment strategies; (3) Results: POPF grade B/C was observed in 39 patients (19.5%). These patients were younger, mainly male, had fewer comorbidities and showed a higher body mass index. Also, they had lower CA-19 levels, a smaller tumor size and softer pancreatic parenchyma. They experienced a worse outcome without affecting the overall mortality rate (10% vs. 6%, p = 0.481), however, this lead to a prolonged postoperative stay (28 (32–36) d vs. 20 (15–28) d, p ≤ 0.001). The majority of patients with POPF grade B/C were able to receive conservative treatment, followed by drainage placement, endoscopic vacuum-assisted therapy (EVT) and surgery. Conservative treatment resulted in a shorter length of the postoperative stay (24 (22–28) d vs. 34 (26–43) d, p = 0.012); (4) Conclusions: Patients developing POPF grade B/C had a worse outcome; however, this did not affect the overall mortality rate. The majority of the patients were able to receive conservative treatment, resulting in a shorter length of their hospital stay.

PurposeThe detection of pancreatic cystic lesions (PCL) causes uncertainty for physicians and patients, and international guidelines are based on low evidence. The extent and perioperative risk of resections of PCL in Germany needs comparison with these guidelines to highlight controversies and derive recommendations.MethodsClinical data of 1137 patients who underwent surgery for PCL between 2014 and 2019 were retrieved from the German StuDoQ|Pancreas registry. Relevant features for preoperative evaluation and predictive factors for adverse outcomes were statistically identified.ResultsPatients with intraductal papillary mucinous neoplasms (IPMN) represented the largest PCL subgroup (N = 689; 60.6%) while other entities (mucinous cystic neoplasms (MCN), serous cystic neoplasms (SCN), neuroendocrine tumors, pseudocysts) were less frequently resected. Symptoms of pancreatitis were associated with IPMN (OR, 1.8; P = 0.012) and pseudocysts (OR, 4.78; P < 0.001), but likewise lowered the likelihood of MCN (OR, 0.49; P = 0.046) and SCN (OR, 0.15, P = 0.002). A total of 639 (57.2%) patients received endoscopic ultrasound before resection, as recommended by guidelines. Malignancy was histologically confirmed in 137 patients (12.0%), while jaundice (OR, 5.1; P < 0.001) and weight loss (OR, 2.0; P = 0.002) were independent predictors. Most resections were performed by open surgery (N = 847, 74.5%), while distal lesions were in majority treated using minimally invasive approaches (P < 0.001). Severe morbidity was 28.4% (N = 323) and 30d mortality was 2.6% (N = 29). Increased age (P = 0.004), higher BMI (P = 0.002), liver cirrhosis (P < 0.001), and esophageal varices (P = 0.002) were independent risk factors for 30d mortality.ConclusionWith respect to unclear findings frequently present in PCL, diagnostic means recommended in guidelines should always be considered in the preoperative phase. The therapy of PCL should be decided upon in the light of patient-specific factors, and the surgical strategy needs to be adapted accordingly.

BACKGROUND:Delayed gastric emptying (DGE) remains the most frequent complication following pancreatoduodenectomy (PD). The present study investigates the influence of delayed gastric emptying on cancer-specific survival after PD.METHODS:We included 267 patients who underwent PD between 2014 and 2021. They were analyzed regarding demographic factors, pre- and perioperative characteristics, surgical complications, and long-term survival.RESULTS:Patients with a higher Charlson Comorbidity Index (CCI) or pre-existing pulmonary disease suffered significantly more from DGE. When experiencing PPH, a prolonged hospital stay, or major overall complications (Clavien-Dindo °III-V) were more common in the DGE group. Tumor size over 3 cm negatively affected survival.CONCLUSIONS:DGE has no influence on long-term survival in PDAC patients, although it prolongs hospital stay.

Zusammenfassung Hintergrund Robotergestützten Rektumresektionen wird nachgesagt, dass sie bekannte Schwierigkeiten der laparoskopischen Rektumchirurgie durch technische Vorteile überwinden und so zu besseren Behandlungsergebnissen führen. Veröffentlichte Studien berichten jedoch sehr heterogene Ergebnisse. Ziel dieser Arbeit ist es daher, festzustellen, ob es eine Klasse-1a-Evidenz für den Vergleich von robotergestützten vs. laparoskopischen Rektumresektionen gibt. Weiterhin möchten wir die Behandlungsergebnisse unserer Klinik mit den berechneten Effekten aus der Literatur vergleichen. Material und Methoden Eine systematische Literaturrecherche nach Klasse-1a-Evidenz wurde durchgeführt und die berechneten Effekte für 7 vorausgewählte Endpunkte wurden miteinander verglichen. Anschließend analysierten wir alle elektiven Rektumresektionen, die zwischen 2017 und 2020 in unserer Klinik durchgeführt wurden, und verglichen die Behandlungsergebnisse mit den Ergebnissen der identifizierten Metaanalysen. Ergebnisse Die Ergebnisse der 7 identifizierten Metaanalysen zeigten keine homogenen Effekte für die Endpunkte Operationszeit und Konversionsrate, während die berechneten Effekte der anderen untersuchten Endpunkte weitgehend konsistent waren. Unsere Patientendaten zeigten, dass robotergestützte Rektumresektionen mit signifikant längeren Operationszeiten assoziiert waren, während die anderen Outcomes kaum von der Operationstechnik beeinflusst wurden. Diskussion Obwohl bereits Klasse-1a-Metaanalysen zum Vergleich von robotergestützten und laparoskopischen Rektumresektionen vorliegen, erlauben diese keine evidenzbasierte Empfehlung zur Bevorzugung einer der beiden Operationstechniken. Die Analyse unserer Patientendaten zeigte, dass die in unserer Klinik erzielten Ergebnisse weitgehend mit den beobachteten Effekten der Metaanalysen übereinstimmen.

Cholangiocarcinoma (CCA) still has a poor prognosis and remains a major therapeutic challenge. When curative resection is not possible, palliative systemic chemotherapy with gemcitabine and platinum derivate as first line followed by a 5-FU doublet combination as second line is the standard therapy. Recently, targeted therapy and immunotherapy have rapidly emerged as personalized therapeutic approaches requiring previous tumor sequencing and molecular profiling. BRCA mutations are well-characterized targets for poly (ADP-ribose) polymerase inhibitors (PARPi). However, BRCA gene mutations in CCA are rare and few data of PARPi in the treatment of CCA are available. Immunotherapy with programmed death receptor-1 (PD-1) has been shown to be effective in combination with chemotherapy or in PD-L1-positive CCA. However, data from immunotherapy combined with targeted therapy, including PARPi, are lacking. In this report, we present the case of a male patient with PD-L1-positive and BRCA2-mutated metastatic intrahepatic cholangiocarcinoma, who was treated with a combined therapy with PARP (PARPi), olaparib, and a PD-1 antibody, pembrolizumab, as second-line therapy after gemcitabine/platinum derivate failure. Combined therapy was able to induce a long-lasting complete remission for over 15 months. The combined therapy was feasible and well tolerated. Only mild anemia and immune-related thyroiditis were observed, which were easily manageable and did not result in discontinuation of olaparib and pembrolizumab. Conclusion The presented case showed substantial clinical activity of a combination with olaparib/pembrolizumab in advanced BRCA2-mutated CCA. Thus, identifying targetable molecular signatures and combinations of targeted therapies with immunotherapy reveals a promising strategy to effectively treat patients with cholangiocarcinoma and should be considered after failure of standard chemotherapy.

Background: To investigate changes over the last decades in the management of postoperative complications following pancreatoduodenectomy (PD) with special emphasis on reoperations, their indications, and outcomes. Methods: 409 patients who underwent PD between 2008 and 2021 were retrospectively analyzed with respect to their need for reoperations (reoperation, n = 81, 19.8% vs. no reoperation, n = 328, 80.2%). The cohort was then compared to a second cohort comprising patients who underwent PD between 1989 and 2007 (n = 285). Results: 81 patients (19.8%) underwent reoperation. The main cause of reoperation was the dehiscence of pancreatogastrostomy (22.2%). Reoperation was associated with a longer duration of the index operation, more blood loss, and more erythrocyte concentrates being transfused. Patients who underwent reoperation showed more postoperative complications and a higher mortality rate (25% vs. 2%, p < 0.001). Compared to the earlier cohort, the observed increase in reoperations did not lead to increased mortality (5% vs. 6%, p = 353). Conclusions: The main cause for reoperation has changed over the last decades and was the dehiscence of pancreatogastrostomy. Associated with a leakage of pancreatic fluid and clinically relevant PF, it remains the most devastating complication following PD. Strategies for prevention and treatment, e.g., by endoscopic vacuum-assisted-closure therapy are of utmost importance.

Background:Prognosis of patients with pancreatic cancer is still extremely poor. First-line palliative therapies with FOLFIRINOX or gemcitabine/nab-paclitaxel have been established in the last decade. In the second-line, 5-FU/LV in combination with nanoliposomal irinotecan (nal-IRI) after gemcitabine has been shown to be effective. However, the use of nal-IRI as third-line therapy after FOLFIRINOX and gemcitabine-based chemotherapies is still controversial. In this study, we report about the use of 5-FU/LV + nal-IRI in a daily practice and analyze whether nal-IRI is an option as third-line therapy after FOLFIRINOX and gemcitabine/nab-paclitaxel.Methods:This is a single center retrospective analysis of patients with irresectable pancreatic cancer who were treated with 5-FU/LV and nal-IRI from 2017 to 2021 as second- or third-line palliative treatment. Overall survival (OS), progression-free survival (PFS) and toxicity were analyzed, and multivariate analysis was used to identify independent prognostic factors.Results:Twenty-nine patients receiving 5-FU/LV and nal-IRI were included in the analysis. The majority of patients (n=19) received 5-FU/nal-IRI as third-line therapy after pre-exposition to FOLFIRINOX and gemcitabine/nab-paclitaxel. Median OS and PFS were 9.33 months (95% CI: 3.37, 15.30) and 2.90 months (95% CI: 1.64, 4.16), respectively. Furthermore, patients receiving nal-IRI + 5-FU/LV as third-line treatment also showed some benefits, with no OS difference compared to second-line patients (9.33 vs. 10.27 months; HR: 1.85; 95% CI: 0.64, 5.41; P=0.253). Adverse effects were similar to reported trials.Conclusions:In our study, the use of 5-FU/nal-IRI in unselected patients with advanced pancreatic cancer showed similar OS, PFS and tolerance as randomized prospective phase II/III trials. Interestingly, the use of 5-FU/nal-IRI seemed to be beneficial in third-line therapy, despite a pre-exposure to non-liposomal irinotecan.

Muscularis Externa Macrophages ( ME -Macs) and enteric glial cells (EGCs) are closely associated cell types in the bowel wall, and important interactions are thought to occur between them during intestinal inflammation. They are involved in developing postoperative ileus (POI), an acute, surgery-induced inflammatory disorder triggered by IL-1 receptor type I (IL1R1)-signaling. In this study, we demonstrate that IL1R1-signaling in murine and human EGCs induces a reactive state, named enteric gliosis, characterized by a strong induction of distinct chemokines, cytokines, and the colony-stimulating factors 1 and 3. Ribosomal tagging revealed enteric gliosis as an early part of POI pathogenesis, and mice with an EGC-restricted IL1R1-deficiency failed to develop postoperative enteric gliosis, showed diminished immune cell infiltration, and were protected from POI. Furthermore, the IL1R1-deficiency in EGCs altered the surgery-induced glial activation state and reduced phagocytosis in macrophages, as well as their migration and accumulation around enteric ganglia. In patients, bowel surgery also induced IL-1-signaling, key molecules of enteric gliosis, and macrophage activation. Together, our data show that IL1R1-signaling triggers enteric gliosis, which results in ME -Mac activation and the development of POI. Intervention in this pathway might be a useful prophylactic strategy in preventing such motility disorders and gut inflammation.

Background: The data about obesity on postoperative outcome after pancreatoduodenectomy (PD) are inconsistent, specifically in relation to gastric motility and delayed gastric emptying (DGE). Methods: Two hundred and eleven patients were included in the study and patients were retrospectively analyzed in respect to pre-existing obesity (obese patients having a body mass index (BMI) ≥ 30 kg/m2 vs. non-obese patients having a BMI < 30 kg/m2, n = 34, 16% vs. n = 177, 84%) in relation to demographic factors, comorbidities, intraoperative characteristics, mortality and postoperative complications with special emphasis on DGE. Results: Obese patients were more likely to develop clinically relevant pancreatic fistula grade B/C (p = 0.008) and intraabdominal abscess formations (p = 0.017). However, clinically relevant DGE grade B/C did not differ (p = 0.231) and, specifically, first day of solid food intake (p = 0.195), duration of intraoperative administered nasogastric tube (NGT) (p = 0.708), rate of re-insertion of NGT (0.123), total length of NGT (p = 0.471) or the need for parenteral nutrition (p = 0.815) were equally distributed. Moreover, mortality (p = 1.000) did not differ between the two groups. Conclusions: Obese patients do not show a higher mortality rate and are not at higher risk to develop DGE. We thus show that in our study, PD is feasible in the obese patient in regard to postoperative outcome with special emphasis on DGE.

Background In recent years substantial progress has been made in the treatment, surveillance and understanding of the pathogenesis of primary sclerosing cholangitis (PSC); however, in most cases liver transplantation (LTX) is still the only curative option for cancer or end-stage liver disease (ELD). In rare cases a partial liver resection is a possible curative treatment of a PSC-associated cholangiocellular carcinoma (CCC). These operations represent a significant additional burden for PSC patients. Objective Due to the rarity of PSC detailed studies regarding hepato-pancreato-biliary (HPB) surgery are lacking. The aim of this study was to analyze the surgical indications and prognosis of PSC patients. Patients and methods A single center retrospective cohort study from 1990 to 2020 was carried out. In this study patients with PSC were included and investigated with respect to factors associated with surgery and the prognosis. Results As a consequence of PSC-associated conditions, in 62 patients (36%) a major HPB operation or explorative laparotomy was necessary. The prevalence of chronic inflammatory bowel disease was significantly higher in these patients (P & x202f;< 0.019). An LTX was carried out in 46 patients (73%) because of ELD. A liver resection (LR) was performed in 8 patients (11%) and 9 patients only underwent an explorative laparotomy. The overall survival in the LTX subgroup was significantly longer than patients who underwent LR and explorative laparotomy (258 months; 95% confidence interval, CI 210-306 months vs. 88 months; 95% CI 16-161 months vs. 13 months; 95% CI 3-23 months; p & x202f;< 0.05, respectively). Conclusion The majority of patients with PSC have to be operated on because of the disease with substantial risks for morbidity and mortality. Curative treatment options are lacking, thus underlining the need for effective early detection and treatment strategies for PSC-CCC.

Background: Biliary complications are common causes of morbidity and mortality after liver transplantation. Material/Methods: From 2013 to 2018, 102 whole-organ liver transplantations were conducted in our department. Patients were closely monitored for biliary complication development. In all suspected cases, patients underwent either endoscopic retrograde cholangiopancreatography or percutaneous transhepatic cholangial drainage. Patients' demographic characteristics, preexisting conditions, and perioperative characteristics, as well as morbidity and mortality, were analyzed. Risk factors for 1-year survival were calculated. Results: Of the 102 patients, 43 (42%) experienced biliary complications. In comparison with patients without biliary complications, patients with biliary complications exhibited the following risk factors: underlying liver disease (viral hepatitis; P=0.009), blood group A (P=0.005), and previous abdominal surgery (P=0.037). Neither perioperative characteristics, especially duration of cold ischemia (P=0.86), nor postoperative course differed between patients with and without biliary complications. Risk factors for mortality within 1 year were cirrhosis caused by entities other than viral hepatitis (P=0.017), cardiac comorbidities (P=0.019), re-transplantation (P=0.032), and reduced organ weight (P=0.002). Biliary complications, postoperative hemorrhage, primary nonfunction, and repeated surgery worsened outcome; moreover, serum bilirubin trough in the first 30 days after transplantation might be prognostic for mortality (P=0.043). Conclusions: Biliary complications adversely affect outcome after liver transplantation. Neither frequency nor outcome of biliary complications was improved by intensified endoscopic evaluation. Patients on the waiting list for liver transplants should also be closely monitored for cardiac comorbidities.