Regulatory T Cell Inhibition by P60 Combined with Adenoviral AFP Transduced Dendritic Cells for Immunotherapy of Hepatocellular Carcinoma.

BACKGROUND & AIMS: Vaccination with tumor-associated antigen-pulsed dendritic cells leads to specific T-cell response against hepatocellular carcinoma. However, clinical response has been shown to be limited. High regulatory T-cell count is associated with poor prognosis and seems to mediate immune tolerance in hepatocellular carcinoma. Forkhead box P3-peptide inhibitor P60 has been shown to specifically inhibit regulatory T-cell function in murine models. Aim of this study was to investigate whether P60 can improve the immune response induced by vaccination with adenovirus-transduced dendritic cells expressing alpha-fetoprotein in subcutaneous and orthotopic murine models for hepatocellular carcinoma. METHODS: Mice developing subcutaneous or orthotopic HCC received daily treatment with P60 starting at different tumor stages. Additionally, mice were vaccinated twice with dendritic cells expressing alpha-fetoprotein. RESULTS: In a preventive setting prior to tumor engraftment, vaccination with alpha-fetoprotein-expressing dendritic cells significantly decreased tumor growth in a subcutaneous model (p = .0256), but no further effects were achieved by addition of P60. However, P60 enhanced the antitumoral effect of a vaccination with alpha-fetoprotein-expressing dendritic cells in established subcutaneous and orthotopic hepatocellular carcinoma characterized by high Treg levels (p = .011). CONCLUSION: In this study, we showed that vaccination with alpha-fetoprotein-expressing dendritic cells in combination with a specific inhibition of regulatory T-cells by using P60 leads to synergistic tumor inhibition and prolonged survival. This emphasizes the importance of regulatory T-cells inhibition for obtaining an effective antitumoral immune response in hepatocellular carcinoma.

Surgical treatment of mechanical bowel obstruction: characteristics and outcomes of geriatric patients compared to a younger cohort.

PURPOSE: Mechanical bowel obstruction (MBO) is one of the most common indications for emergency surgery. Recent research justifies the method of attempting 3-5 days of nonoperative treatment before surgery. However, little is known about specific characteristics of geriatric patients undergoing surgery compared to a younger cohort. We aimed to analyze patients with MBO that required surgery, depending on their age, to identify potential targets for use in the reduction in complications and mortality in the elderly. METHODS: Thirty-day and in-hospital mortality were determined as primary outcome. We retrospectively identified all patients who underwent surgery for MBO at the University Hospital of Bonn between 2009 and 2019 and divided them into non-geriatric (40-74 years, n = 224) and geriatric (≥ 75 years, n = 88) patients, using the chi-squared-test and Mann-Whitney U test for statistical analysis. RESULTS: We found that geriatric patients had higher 30-day and in-hospital mortality rates than non-geriatric patients. As secondary outcome, we found that they experienced a longer length of stay (LOS) and higher complication rates than non-geriatric patients. Geriatric patients who suffered from large bowel obstruction (LBO) had a higher rate of bowel resection, stoma creation, and a higher 30-day mortality rate. The time from admission to surgery was not shown to be crucial for the outcome of (geriatric) patients. CONCLUSION: Geriatric patients suffering from mechanical bowel obstruction that had to undergo surgery had higher mortality and morbidity than non-geriatric patients. Especially in regard to geriatric patients, clinicians should treat patients in a risk-adapted rather than time-adapted manner, and conditions should be optimized before surgery.

Transcutaneous vagal nerve simulation to reduce a systemic inflammatory response syndrome and the associated intestinal failure: study protocol of a prospective, two-armed, sham-controlled, double-blinded trial in healthy subjects (the NeuroSIRS-Study).

PURPOSE: Surgery initiates pro-inflammatory mediator cascades leading to a variably pronounced sterile inflammation (SIRS). SIRS is associated with intestinal paralysis and breakdown of intestinal barrier and might result in abdominal sepsis. Technological progress led to the development of a neurostimulator for transcutaneous auricular vagal nerve stimulation (taVNS), which is associated with a decline in inflammatory parameters and peristalsis improvement in rodents and healthy subjects via activation of the cholinergic anti-inflammatory pathway. Therefore, taVNS might be a strategy for SIRS prophylaxis. METHODS: The NeuroSIRS-Study is a prospective, randomized two-armed, sham-controlled, double-blind clinical trial. The study is registered at DRKS00016892 (09.07.2020). A controlled endotoxemia is used as a SIRS-mimicking model. 2 ng/kg bodyweight lipopolysaccharide (LPS) will be administered after taVNS or sham stimulation. The primary objective is a reduction of clinical symptoms of SIRS after taVNS compared to sham stimulation. Effects of taVNS on release of inflammatory cytokines, intestinal function, and vital parameters will be analyzed. DISCUSSION: TaVNS is well-tolerated, with little to no side effects. Despite not fully mimicking postoperative inflammation, LPS challenge is the most used experimental tool to imitate SIRS and offers standardization and reproducibility. The restriction to healthy male volunteers exerts a certain bias limiting generalizability to the surgical population. Still, this pilot study aims to give first insights into taVNS as a prophylactic treatment in postoperative inflammation to pave the way for further clinical trials in patients at risk for SIRS. This would have major implications for future therapeutic approaches.

Safety and Suitability of the SmartPill® after Abdominal Surgery: Results of the Prospective, Two-Armed, Open-Label PIDuSA Trial.

INTRODUCTION: Postoperative ileus (POI) is a common complication after abdominal surgery. Until today, an evidence-based treatment of prolonged POI is still lacking, which can be attributed to the poor quality of clinical trials. Various different surrogate markers used to define POI severity are considered to be the cause of low-quality trials making it impossible to derive treatment recommendation. The SmartPill®, which is able to record pH values, temperature and pressure after ingestion, could be an ideal tool to measure transit times and peristalsis and therefore analyze POI severity. Unfortunately, the device has no approval for postoperative use due to safety concerns. The primary objective of the study is to determine safety of the SmartPill® in patients undergoing surgery. Secondary objectives were the quality of the recorded data and the suitability of the SmartPill® for analyzing intestinal motility after different surgical procedures. METHODS: The PIDuSA Study is a prospective, 2-arm, open-label trial. At the end of surgery, the SmartPill® was applied to 49 patients undergoing abdominal surgery having a high risk for impaired intestinal motility and 15 patients undergoing extra-abdominal surgery. Patients were visited daily to access safety data of the SmartPill® on the basis of adverse and serious adverse events (AEs/SAEs). Suitability and data quality were investigated by analyzing data completeness and feasibility to determine transit times and peristalsis for all sections of the gastrointestinal tract. RESULTS: In total, 179 AEs and 8 SAEs were recorded throughout the study affecting 42 patients in the abdominal (158 AEs) and 9 patients in the extra-abdominal surgery group (21 AEs, p = 0.061); none of them were device related. Primary capsule failure was observed in 5 patients, ultimately resulting in an impossibility of data analysis in only 3 patients (4.4%). 9% of the recorded data were incomplete due to the patient's incompliance in keeping the receiver close to the body. In 3 patients (4.4%), isolated small bowel transit could not be determined due to pH alterations as a result of prolonged POI. DISCUSSION: Our study demonstrates that the use of the SmartPill® is safe after surgery but requires a reasonable patient compliance to deliver meaningful data. An objective analysis of transit times and peristalsis was possible irrespective of type and site of surgery in over 95% indicating that the SmartPill® has the potential to deliver objective parameters for POI severity in future clinical trials. However, in some patients with prolonged POI, analysis of small bowel transit could be challenging.

[Evaluation of the Effectiveness of a Standard Operating Procedure (SOP) for the Perioperative Management of Colorectal Surgery]. / Evaluation der Effektivität einer Standard Operating Procedure (SOP) zur perioperativen Therapie bei kolorektalen Operationen.

INTRODUCTION: In recent years, perioperative care of patients after colorectal surgery has been increasingly standardised according to the fast-track concept and is accepted as a structured method of care to reduce perioperative complications. Indeed, initial studies have indicated that there is a long-term favourable effect on the oncological outcome, if the adherence to the individual measures is at least 70%. Even though there is unambiguous evidence for the efficacy of the modern perioperative treatment concept, it is often difficult to comply with the protocol during normal clinical work, particularly in Germany. The objective of this study was to record the rate of compliance before and after the introduction of the SOP and to evaluate its efficacy. METHODS: We performed a retrospective analysis of the patient data after all elective colorectal surgery in the Bonn University Hospital from 2017 to 2020. 153 patients were operated on before the implementation of the SOP in January 2019 (group I); the remaining 153 patients were operated on after the implementation of the SOP and received appropriate care (group II). Compliance to the protocol was analysed for both the individual key interventions and the overall concept. RESULTS: There was significant improvement in the compliance for both the individual measures (prehabilitation group I: 5.9%, group II: 42.5%, p < 0.001; preparation of the intestine I: 16.5%, II: 73.9%, p < 0.001; intraoperative volume management I: 14,00 ml/kg BW/h, II: 9.12 ml/kg BW/h, p < 0.001, BW: body weight; minimally invasive surgical technique I: 53.6%, II: 73.9%, p < 0.001; etc.) and for the overall perioperative treatment concept (I: 39%, II: 54%, p = 0.02). However, we fell far short of compliance of at least 70%. Nevertheless, patient autonomy was achieved earlier after introduction of the SOP (I: day 15, II: day 9, p < 0.001) and the postoperative hospital stay was shortened (I: 14 [6 - 99] days, II 11 [4 - 64] days; p = 0.007). CONCLUSION: Although the implementation of the SOP led to significant improvements, further optimisation is required to attain the recommended protocol compliance of 70%. Measures within the hospital could include foundation of an interdisciplinary fast-track team and a specialised nurse as the connecting link between the patients, nursing and physicians. On the other hand, implementation throughout Germany can only be achieved by more influential actions. One possible support would be the S3 guideline on perioperative management of gastrointestinal tumours, which is under development. This could, for example, be used to support argumentation with funding providers.

[The Impact of Supra- and Infracolic Reconstruction on Delayed Gastric Emptying Following Pancreatoduodenectomy]. / Varianten der retrokolischen Rekonstruktion nach partieller Pankreatoduodenektomie und deren Einfluss auf die Magenentleerung ­ infra- oder suprakolisch.

BACKGROUND: Delayed gastric emptying (DGE) is the most frequent complication following pancreatoduodenectomy. While antecolic and retrocolic reconstruction does not influence the occurrence of DGE, infracolic reconstruction might alleviate DGE due to the vertical position of the distal stomach compared to supracolic reconstruction. Supra- and infracolic reconstruction have not yet been compared. PATIENTS: 138 patients underwent pylorus-preserving pancreatoduodenectomy with retrocolic reconstruction at our department between 2011 and 2017. Of these, 105 were reconstructed with supracolic duodenoenterostomy and 33 with infracolic duodenoenterostomy. Patients were analysed with respect to demographic factors, diagnosis, pre-existing conditions, intraoperative characteristics, hospital stay and morbidity and mortality with special emphasis on DGE. All complications were classified according to the definitions of the International Study Group on Pancreatic Surgery. RESULTS: The two groups were comparable with respect to diagnosis, medical history, intraoperative characteristics, morbidity and mortality. DGE was equally distributed between supra- and infracolic reconstruction (DGE stage A/B/C25/14/10 vs. 12/5/2, p = 0.274). With DGE, intensive care unit stay (p = 0.007) and hospital stay (p = 0.001) are significantly delayed. Risk factor analysis showed that pre-existing diabetes (p = 0.047) and major complications (Clavien stage III - V, p = 0.048) are risk factors for DGE, while the use of somatostain-analogues seems to have a protective effect (p = 0.021). CONCLUSION: Supra- or infracolic reconstruction does not influence the frequency of DGE following pancreatoduodenectomy. When DGE occurs, hospital stay is delayed. Somatostatin analogues may act prophylactically on DGE.

Brentuximab vedotin exerts profound antiproliferative and pro-apoptotic efficacy in CD30-positive as well as cocultured CD30-negative germ cell tumour cell lines.

Prognosis in patients suffering from high-risk, refractory and relapsed germ cell tumours (GCT) often comprising of CD30-positive embryonal carcinoma (EC) components remains poor. Thus, novel treatment strategies are warranted. The antibody-drug conjugate (ADC) brentuximab vedotin delivers the potent antimitotic drug monomethyl auristatin E (MMAE) to CD30-expressing tumour cells. After CD30 binding, internalization and intracellular linker cleavage cytotoxic MMAE can efflux and eradicate neighbouring CD30-negative cells. To analyse cytotoxicity and a potential bystander effect of brentuximab vedotin in GCT, we established an in vitro coculture model mimicking GCT of heterogeneous CD30 positivity and measured cell viability, proliferation and apoptosis after exposure to brentuximab vedotin and unbound MMAE by MTS- and flow cytometry-based CFSE/Hoechst assay. CD30 expression being assessed by quantitative RT-PCR and immunohistochemistry was apparent in all EC cell lines with different intensity. Brentuximab vedotin abrogates cell viability of CD30-positive GCT27 EC line exerting marked time-dependent antiproliferative and pro-apoptotic activity. CD30-negative JAR cultured alone barely responds to brentuximab vedotin, while in coculture with GCT27 brentuximab vedotin induces clear dose-dependent cytotoxicity. Cellular proliferation and cell death are significantly enhanced in CD30-negative JAR cocultured with CD30-positive GCT27 compared to JAR cultured alone in proof of substantial bystander activity of brentuximab vedotin in CD30-negative GCT. We present first evidence that in an in vitro model mimicking GCT of heterogeneous histology, brentuximab vedotin exerts potent antiproliferative and pro-apoptotic activity against both CD30-positive as well as CD30-negative GCT subsets. Our results strongly support translational efforts to evaluate clinical efficacy of brentuximab vedotin in high-risk GCT of heterogeneous CD30 positivity.

[Have Multimodal and Perioperative Therapeutic Strategies Changed the Survival after Oncological Oesophageal Surgery in the Last Two Decades? A Retrospective Cohort Analysis over 23 Years]. / Haben multimodale und perioperative Therapiestrategien das Überleben nach onkologischer Ösophaguschirurgie in den letzten 2 Dekaden verändert? Eine retrospektive Kohortenanalyse über 23 Jahre.

BACKGROUND: Esophageal malignoma is among the most frequent causes for cancer-related deaths. The only definite curative therapy is esophagectomy embedded in various multimodal treatment regimens. The aim of this study was to evaluate long-term development after esophageal surgery in the last two decades in order to observe possible trends and their influence on short, medium and long term survival. PATIENTS AND METHODS: Cases of 301 patients who underwent esophagectomy between 1989 and 2012 were analysed retrospectively. To investigate possible changes in perioperative management and their influence on prognosis patients were divided into two cohorts (A: surgery between 1989 and 2000; B: surgery between 2001 and 2012) and further analyzed with regard to demographics, tumor entity, stage, complications and survival. Statistics were conducted to compare both groups while p ≤ 0.05 was regarded as statistically significant. RESULTS: In cohort B patients were significantly older compared to cohort A and underwent surgery in earlier tumor stages with a higher lymphnode yield. Also an increased incidence of adenocarcinoma was observed. While overall morbidity did not change significantly, a decreased rate of anastomotic leakage was observed in cohort B (5.5%) compared to cohort A (12.3%) accompanied by a simultaneous increase in cardiac events (A: 3.6% vs. B: 12.3%). Overall 30-days-mortality was 2.7% and decreased significantly from 5% in cohort A to 0.7% in cohort B (p = 0.05). Median survival was 46 ± 7 month in cohort A, in cohort B an increase could be observed (53 ± 7 months, p = 0.03). By univariate analysis we could demonstrate that stage, affected lymph nodes, lymphnode ratio (LNR) and incidence of postoperative complications were significant predictors for the survival whereas in multivariate analysis T-stage, R-status and LNR were independent predictors for patients outcome. CONCLUSION: Patients undergoing esophageal resection for cancer nowadays are older than in the past decades. Earlier cancer diagnosis, more radical surgical techniques with an extended lymphnode dissection, a decrease in anastomotic leakage and an improved perioperative care seem to compensate for this potential demographic disadvantage. The most important independent predictor of outcome after esophageal resection is the LNR.

[The Devascularisation Procedure for the Treatment of Fundic and Oesophageal Varices in Portal Hypertension - a Retrospective Analysis of 55 Cases]. / Die Devaskularisationsoperation zur Behandlung von Fundus- und Ösophagusvarizen bei portaler Hypertension ­ eine retrospektive Analyse von 55 Fällen.

BACKGROUND: The most dangerous complication of portal hypertension is the formation of oesophageal varices, as the risk of bleeding is up to 80%. In order to reduce pressure reduction in the portosystemic circulation and as secondary prophylaxis, the TIPSS procedure has proven successful. In patients with portal vein thrombosis, portosystemic shunt surgery is possible to reduce the risk of variceal bleeding. However, if thrombosis of the mesentericoportal axis or hepatic encephalopathy is imminent, interventional or surgical creation of a portosystemic shunt is contraindicated. As a last resort to avoid recurrent bleeding or in case of inexorable bleeding, a devascularisation procedure may be indicated. The aim of this study was to investigate perioperative complications, morbidity and mortality, the incidence of postoperative recurrent bleeding, and patient survival after devascularisation surgery. PATIENTS AND METHODS: We retrospectively analysed 55 patients with a history of variceal haemorrhage or acute bleeding without the possibility of an invasive or operative portosystemic shunt for complication rate, recurrent variceal recurrence, rebleeding and survival. RESULTS: While complications for elective surgery were 61%, they increased significantly in emergency surgeries (75%, p = 0.002), especially for severe complications (Dindo/Clavien grade III - V° [14 vs. 58%, p = 0.002]). Devascularisation significantly reduced varicosis occurrence. Furthermore, only 16% of patients suffered recurrent bleeding in a follow-up period of up to 24 years. Median survival (MS) after devascularisation surgery was 169 ± 23 months. After elective surgery, MS was 194 ± 25 months, but after emergency surgery only 49 ± 16 months. No patient showed any hepatic encephalopathy during their hospital stay. DISCUSSION: Devascularisation surgery is well suited for secondary prophylaxis in patients with fundic and oesophageal varices and portal hypertension with no possibility of portosystemic shunt or with impending hepatic encephalopathy. However, if the operation is performed in an emergency situation, significantly more major complications occur and the outcome is significantly worse. Therefore, especially in the absence of an opportunity of lowering pressure in the portal venous system and with progressive varices, elective devascularisation should be considered at an early stage.

[Robot-assisted rectal resections-Scoping review for level 1a evidence and retrospective analysis of in-clinic data]. / Robotergestützte Rektumresektionen ­ Scoping-Review für Klasse-1a-Evidenz und retrospektive Analyse klinikinterner Daten.

BACKGROUND: Robot-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 METHODS: A 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. RESULTS: The 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. DISCUSSION: Although 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.

Predictors of Morbidity and Mortality After Colorectal Surgery in Patients With Cirrhotic Liver Disease-A Retrospective Analysis of 54 Cases at a Tertiary Care Center.

Background: Despite various existing scores that predict morbidity and mortality of patients with cirrhotic liver disease (CLD), data on specific risk stratification of patients with CLD undergoing colorectal surgery (CRS) are rare. The aim of this study was to assess in-hospital morbidity and mortality of patients with liver cirrhosis scheduled for CRS, with specific focus on possible pitfalls of surgery in this special cohort. Methods: Between 1996 and 2018, 54 patients with CLD undergoing CRS were identified and included in this study cohort. Postoperative morbidity and mortality were assessed using the Clavien/Dindo (C/D) classification as well as by type of complication. Univariate and multivariate analyses were performed to analyze the predictive factors for increased postoperative morbidity. Results: Of the patients, 37% patients died during the procedure or postoperatively. Major complications were seen in 23.1% of patients (>C/D IIIb). Patients with Child B or C cirrhosis as well as patients undergoing emergency surgery experienced significantly more major complications (p = 0.04 and p = 0.023, respectively). The most common complications were bleeding requiring blood transfusion (51.1%) and cardiocirculatory instability due to bleeding or sepsis (44.4%). In 53.7% of patients, an anastomosis was created without a protective ostomy. Anastomotic leakage occurred in 20.7% of these patients. Multivariate analysis showed that a primary anastomosis without a protective ostomy was the strongest risk factor for major complications (p = 0.042). Discussion: Morbidity and mortality after CRS in patients with CLD remains high and is not only influenced by liver function but also by surgical variables. Considering the high rate of anastomotic leakage, creating a protective or definitive ostomy must be considered with regard to the underlying pathology, the extent of CLD, and the patient's condition. Moreover, our data suggest that surgery in these most fragile patients should be performed only in experienced centers with immediate contact to hepatologists and experts in hemostasis.

Model for end-stage liver disease underestimates mortality of patients with acute-on-chronic liver failure waiting for liver transplantation.

BACKGROUND AND AIMS: Patients with acute-on-chronic liver failure (ACLF) show excess mortality in MELD-Na based organ allocation for liver transplantation (LT). Whether MELD-based allocation in the Eurotransplant region similarly underprioritizes ACLF patients is unknown. METHODS: 428 patients listed for LT from 01/2010 to 02/2021 at a tertiary center in Germany were screened and 209 patients included as derivation (n = 123) and validation cohort (n = 86). Competing risk analysis for waitlist mortality and LT as competing events was performed. RESULTS: 90-day waitlist mortality for patients with MELD < and ≥ 25 at baseline was 9% vs. 33%, respectively (p = 0.009). Competing risk analysis shows significantly higher 90-day waitlist mortality in patients listed with ACLF compared to those without ACLF (p = 0.021) in the low MELD stratum. Probability of LT was similar between the two groups (p = 0.91). In the high MELD group, 90-day waitlist mortality and rates of LT were not significantly different between patients with and without ACLF (31% vs. 20%, p = 0.55 and 59% vs. 60%, p = 0.72, respectively). Post-transplant survival was similar between patients with and without ACLF. This result was confirmed in the validation cohort. CONCLUSION: MELD-based organ allocation in the Eurotransplant region underestimates waitlist mortality in patients with ACLF in lower MELD ranges.

Prognostic value of primary tumor sidedness in patients with non-metastatic IBD related CRC - Is it the exception to the rule?

BACKGROUND: Although primary tumor sidedness (PTS) has a known prognostic role in sporadic colorectal cancer (CRC), its role in Inflammatory Bowel Disease related CRC (IBD-CRC) is largely unknown. Thus, we aimed to evaluate the prognostic role of PTS in patients with IBD-CRC. METHODS: All eligible patients with surgically treated, non-metastatic IBD-CRC were retrospectively identified from institutional databases at ten European and Asian academic centers. Long term endpoints included recurrence-free (RFS) and overall survival (OS). Multivariable Cox proportional hazard regression as well as propensity score analyses were performed to evaluate whether PTS was significantly associated with RFS and OS. RESULTS: A total of 213 patients were included in the analysis, of which 32.4% had right-sided (RS) tumors and 67.6% had left-sided (LS) tumors. PTS was not associated with OS and RFS even on univariable analysis (5-year OS for RS vs LS tumors was 68.0% vs 77.3%, respectively, p = 0.31; 5-year RFS for RS vs LS tumors was 62.8% vs 65.4%, respectively, p = 0.51). Similarly, PTS was not associated with OS and RFS on propensity score matched analysis (5-year OS for RS vs LS tumors was 82.9% vs 91.3%, p = 0.79; 5-year RFS for RS vs LS tumors was 85.1% vs 81.5%, p = 0.69). These results were maintained when OS and RFS were calculated in patients with RS vs LS tumors after excluding patients with rectal tumors (5-year OS for RS vs LS tumors was 68.0% vs 77.2%, respectively, p = 0.38; 5-year RFS for RS vs LS tumors was 62.8% vs 59.2%, respectively, p = 0.98). CONCLUSIONS: In contrast to sporadic CRC, PTS does not appear to have a prognostic role in IBD-CRC.

Normothermic Machine Perfusion (NMP) of the Liver - Current Status and Future Perspectives.

A shortage of available organs for liver transplantation has led transplant surgeons and researchers to seek for innovative approaches in hepatoprotection and improvement of marginal allografts. The most exciting development in the past decade has been continuous mechanical perfusion of livers with blood or preservation solution to mitigate ischemia-reperfusion injury in contrast to the current standard of static cold storage. Two variations of machine perfusion have emerged in clinical practice. During hypothermic oxygenated perfusion the liver is perfused using a red blood cell-free perfusate at 2-10°C. In contrast, normothermic machine perfusion mimics physiologic liver perfusion using a red blood cell-based solution at 35.5-037.5°C, offering a multitude of potential advantages. Putative effects of normothermic perfusion include abrogation of hyperfibrinolysis after reperfusion and inflammation, glycogen repletion, and regeneration of adenosine triphosphate. Research in normothermic machine perfusion focuses on development of biomarkers predicting allograft quality and susceptibility to ischemia-reperfusion injury. Moreover, normothermic perfusion of marginal allografts allows for application of a variety of therapeutic interventions potentially enhancing organ quality. Both methods need to be subjected to translational investigation and evaluation in clinical trials. A clear advantage is transformation of an emergency procedure at night into a planned daytime surgery. Current clinical trials suggest that normothermic perfusion not only increases the use of hepatic allografts but is also associated with milder ischemia-reperfusion injury, resulting in a reduced risk of early allograft dysfunction and less biliary complications, including ischemic cholangiopathy, compared to static cold storage. The aim of this review is to give a concise overview of normothermic machine perfusion and its current applications, benefits, and possible advances in the future.

Electrical vagus nerve stimulation as a prophylaxis for SIRS and postoperative ileus.

Abdominal surgery results in an activation of immune cells of the bowel wall and a consecutive cytokine and nitric oxide (NO) release leading to an inflammation of the muscularis externa and a bowel paralysis, the so-called postoperative ileus (POI). In addition to the local inflammation, major surgical trauma can also lead to a variable pronounced systemic inflammation up to its maximum variant, the systemic inflammatory response syndrome (SIRS), with hypotension, capillary leak and a breakdown of the intestinal barrier function followed by multi-organ dysfunction (MODS). Until now, neither for SIRS nor for POI, a prophylaxis or an evidence-based treatment exists. Since the pioneering work from Kevin Tracey and his group in the late 90s characterizing the role of the vagus nerve in inflammation and describing the cholinergic anti-inflammatory pathway (CAIP) for the first time, substantial efforts have been made in the research field of neuro-immune interactions. Today, the anti-inflammatory potential of vagus nerve stimulation is moving more and more into focus resulting in new therapeutic approaches. This review focuses on the role of the CAIP in the development of SIRS and POI. Furthermore, new therapeutic options like transcutaneous vagus nerve stimulation are highlighted.

Risk Factors for Postoperative Morbidity and Mortality after Small Bowel Surgery in Patients with Cirrhotic Liver Disease-A Retrospective Analysis of 76 Cases in a Tertiary Center.

(1) Purpose: As it is known, patients with liver cirrhosis (LC) undergoing colon surgery or hernia surgery have high perioperative morbidity and mortality. However, data about patients with LC undergoing small bowel surgery is lacking. This study aimed to analyze the morbidity and mortality of patients with LC after small bowel surgery in order to determine predictive risk factors for a poor outcome. (2) Methods: A retrospective analysis was performed of all patients undergoing small bowel surgery between January 2002 and July 2018 and identified 76 patients with LC. Postoperative complications were analyzed using the classification of Dindo/Clavien (D/C) and further subdivided (hemorrhage, pulmonary complication, wound healing disturbances, renal failure). A total of 38 possible predictive factors underwent univariate and multivariate analyses for different postoperative complications and in-hospital mortality. (3) Results: Postoperative complications [D/C grade ≥ II] occurred in 90.8% of patients and severe complications (D/C grade ≥ IIIB) in 53.9% of patients. Nine patients (11.8%) died during the postoperative course. Predictive factors for overall complications were "additional surgery" (OR 5.3) and "bowel anastomosis" (OR 5.6). For postoperative mortality, we identified the model of end-stage liver disease (MELD) score (OR 1.3) and portal hypertension (OR 5.8) as predictors. The most common complication was hemorrhage, followed by pulmonary complications, hydropic decompensation, renal failure, and wound healing disturbances. The most common risk factors for those complications were portal hypertension (PH), poor liver function, emergency or additional surgery, ascites, and high ASA score. (4) Conclusions: LC has a devastating influence on patients' outcomes after small bowel resection. PH, poor liver function, high ASA score, and additional or emergency surgery as well as ascites were significant risk factors for worse outcomes. Therefore, PH should be treated before surgery whenever possible. Expansion of the operation should be avoided whenever possible and in case of at least moderate preoperative ascites, the creation of an anastomotic ostomy should be evaluated to prevent leakages.