[Diagnosis and treatment of Dunbar syndrome]. / Diagnostik und Therapie des Dunbar-Syndroms.

The rare Dunbar syndrome or medial arcuate ligament syndrome (MALS) is defined as compression of the celiac trunk and/or ganglion by the medial arcuate ligament. It is often diagnosed after patients have suffered for a long time and is characterized by intermittent food-related pain, nausea, and unexplained weight loss. After exclusion of other causes of the above symptoms by gastroscopy, colonoscopy, CT, or MRI, the gold standard for diagnosis is dynamic color-coded duplex sonography, which may be supplemented by CT or MR angiography. The treatment of choice is a laparoscopic division of the arcuate ligament at the celiac trunk, although percutaneous transluminal angioplasty (PTA) with stent implantation may be performed in cases of postoperative persistence of symptoms or recurrent stenosis. Since symptoms persist postoperatively in up to 50% of cases, strict indication and complete diagnosis in designated centers are of great importance for successful treatment.

Perioperative therapy with FLOT4 significantly increases survival in patients with gastroesophageal and gastric cancer in a large real-world cohort.

In 2019, the FLOT4 protocol was established as the new standard for perioperative therapy in patients with locally advanced gastroesophageal and gastric cancer. Whether this protocol is beneficial in a real-world setting remains a question with limited answers to date. In our study, a large cohort of unselected patients treated with FLOT4 was analyzed and compared to protocols based on 5-FU/platinum derivative. This retrospective analysis included patients with locally advanced gastroesophageal and gastric cancer treated with perioperative FLOT or 5-FU/platinum derivative at University Hospital, Bonn between 2010 and 2022 in a curative setting (n = 99). Overall survival, disease-free survival, therapy response and therapy complications were analyzed. Patients treated with FLOT showed a statistically significant longer median overall survival of 57.8 vs 28.9 months (HR: 0.554, 95% CI: 0.317-0.969, P = .036). Moreover, pathological tumor regression (pTR) was significantly higher in the FLOT group compared to the 5-FU/platinum group (P = .001). Subgroup analysis showed a favorable survival benefit for the FLOT vs 5-FU/platinum derivate in patients with AEG and non-signet cell carcinoma. Overall, FLOT was tolerated well but CTCAE ≥3 grade neutropenia and diarrhea occurred more often within the FLOT group. Similar to the prospective phase II/III trials, FLOT4 was the best protocol for patients with locally advanced gastroesophageal and gastric cancer as perioperative therapy in terms of overall survival and pathological response rate compared to 5-FU/platinum derivative protocols. Interestingly, patients with gastroesophageal cancer benefitted more from this therapy. In contrast, patients with signet ring cells appear not to benefit from addition of docetaxel.

ß-adrenergic signaling triggers enteric glial reactivity and acute enteric gliosis during surgery.

BACKGROUND: Enteric glia contribute to the pathophysiology of various intestinal immune-driven diseases, such as postoperative ileus (POI), a motility disorder and common complication after abdominal surgery. Enteric gliosis of the intestinal muscularis externa (ME) has been identified as part of POI development. However, the glia-restricted responses and activation mechanisms are poorly understood. The sympathetic nervous system becomes rapidly activated by abdominal surgery. It modulates intestinal immunity, innervates all intestinal layers, and directly interfaces with enteric glia. We hypothesized that sympathetic innervation controls enteric glia reactivity in response to surgical trauma. METHODS: Sox10iCreERT2/Rpl22HA/+ mice were subjected to a mouse model of laparotomy or intestinal manipulation to induce POI. Histological, protein, and transcriptomic analyses were performed to analyze glia-specific responses. Interactions between the sympathetic nervous system and enteric glia were studied in mice chemically depleted of TH+ sympathetic neurons and glial-restricted Sox10iCreERT2/JellyOPfl/+/Rpl22HA/+ mice, allowing optogenetic stimulation of ß-adrenergic downstream signaling and glial-specific transcriptome analyses. A laparotomy model was used to study the effect of sympathetic signaling on enteric glia in the absence of intestinal manipulation. Mechanistic studies included adrenergic receptor expression profiling in vivo and in vitro and adrenergic agonism treatments of primary enteric glial cell cultures to elucidate the role of sympathetic signaling in acute enteric gliosis and POI. RESULTS: With ~ 4000 differentially expressed genes, the most substantial enteric glia response occurs early after intestinal manipulation. During POI, enteric glia switch into a reactive state and continuously shape their microenvironment by releasing inflammatory and migratory factors. Sympathetic denervation reduced the inflammatory response of enteric glia in the early postoperative phase. Optogenetic and pharmacological stimulation of ß-adrenergic downstream signaling triggered enteric glial reactivity. Finally, distinct adrenergic agonists revealed ß-1/2 adrenoceptors as the molecular targets of sympathetic-driven enteric glial reactivity. CONCLUSIONS: Enteric glia act as early responders during post-traumatic intestinal injury and inflammation. Intact sympathetic innervation and active ß-adrenergic receptor signaling in enteric glia is a trigger of the immediate glial postoperative inflammatory response. With immune-activating cues originating from the sympathetic nervous system as early as the initial surgical incision, adrenergic signaling in enteric glia presents a promising target for preventing POI development.

Persisting dental foci increase the risk for bacterial infections before and after liver transplant.

BACKGROUND: Patients awaiting liver transplant are usually assessed for presence of dental foci to prevent bacterial infection post-transplant, but evidence to support dental examination and treatment is limited. We investigated if treatment of dental foci decreased bacterial infections before and after transplant. METHODS: Patients transplanted at the university hospital of Bonn were retrospectively assessed for occurrence of bacterial infections before and after transplant according to presence and treatment of dental foci. RESULTS: 35/110 patients showed good oral health, 39/110 patients received dental care and 36/110 patients did not receive dental care despite poor oral health. Patients with alcohol-associated liver disease presented with the highest rate of dental foci. Bleeding complications due to oral care occurred in five patients with poor coagulation. After transplant, the number of infections per patient was higher in patients with poor oral health (2.9) compared to patients after dental care (1.9) or with good oral health (1.8) (p = .02), with streptococcal infections being more frequent in patients with poor oral health. Before transplant, bacterial infections, in particular bacteraemia and spontaneous bacterial peritonitis, were also more common in patients with untreated dental foci. Streptococci and Staphylococci were more often detected in patients with dental foci. Dental treatment was associated with a reduction in bacterial infections. CONCLUSION: Presence of dental foci is associated with an increased risk for bacterial infections not only after but also before liver transplant. Dental treatment might be a safe and effective procedure to mitigate this risk.

Preoperative combined mechanical and oral antibiotic bowel preparation for preventing complications in elective colorectal surgery.

BACKGROUND: The success of elective colorectal surgery is mainly influenced by the surgical procedure and postoperative complications. The most serious complications include anastomotic leakages and surgical site infections (SSI)s, which can lead to prolonged recovery with impaired long-term health.  Compared with other abdominal procedures, colorectal resections have an increased risk of adverse events due to the physiological bacterial colonisation of the large bowel. Preoperative bowel preparation is used to remove faeces from the bowel lumen and reduce bacterial colonisation. This bowel preparation can be performed mechanically and/or with oral antibiotics. While mechanical bowel preparation alone is not beneficial, the benefits and harms of combined mechanical and oral antibiotic bowel preparation is still unclear. OBJECTIVES: To assess the evidence for the use of combined mechanical and oral antibiotic bowel preparation for preventing complications in elective colorectal surgery. SEARCH METHODS: We searched MEDLINE, Embase, CENTRAL and trial registries on 15 December 2021. In addition, we searched reference lists and contacted colorectal surgery organisations. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of adult participants undergoing elective colorectal surgery comparing combined mechanical and oral antibiotic bowel preparation (MBP+oAB) with either MBP alone, oAB alone, or no bowel preparation (nBP). We excluded studies in which no perioperative intravenous antibiotic prophylaxis was given. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures as recommended by Cochrane. Pooled results were reported as mean difference (MD) or risk ratio (RR) and 95 % confidence intervals (CIs) using the Mantel-Haenszel method. The certainty of the evidence was assessed with GRADE. MAIN RESULTS: We included 21 RCTs analysing 5264 participants who underwent elective colorectal surgery. None of the included studies had a high risk of bias, but two-thirds of the included studies raised some concerns. This was mainly due to the lack of a predefined analysis plan or missing information about the randomisation process. Most included studies investigated both colon and rectal resections due to malignant and benign surgical indications. For MBP as well as oAB, the included studies used different regimens in terms of agent(s), dosage and timing.  Data for all predefined outcomes could be extracted from the included studies. However, only four studies reported on side effects of bowel preparation, and none recorded the occurrence of adverse effects such as dehydration, electrolyte imbalances or the need to discontinue the intervention due to side effects. Seventeen trials compared MBP+oAB with sole MBP. The incidence of SSI could be reduced through MBP+oAB by 44% (RR 0.56, 95% CI 0.42 to 0.74; 3917 participants from 16 studies; moderate-certainty evidence) and the risk of anastomotic leakage could be reduced by 40% (RR 0.60, 95% CI 0.36 to 0.99; 2356 participants from 10 studies; moderate-certainty evidence). No difference between the two comparison groups was found with regard to mortality (RR 0.87, 95% CI 0.27 to 2.82; 639 participants from 3 studies; moderate-certainty evidence), the incidence of postoperative ileus (RR 0.89, 95% CI 0.59 to 1.32; 2013 participants from 6 studies, low-certainty of evidence) and length of hospital stay (MD -0.19, 95% CI -1.81 to 1.44; 621 participants from 3 studies; moderate-certainty evidence). Three trials compared MBP+oAB with sole oAB. No difference was demonstrated between the two treatment alternatives in terms of SSI (RR 0.87, 95% CI 0.34 to 2.21; 960 participants from 3 studies; very low-certainty evidence), anastomotic leakage (RR 0.84, 95% CI 0.21 to 3.45; 960 participants from 3 studies; low-certainty evidence), mortality (RR 1.02, 95% CI 0.30 to 3.50; 709 participants from 2 studies; low-certainty evidence), incidence of postoperative ileus (RR 1.25, 95% CI 0.68 to 2.33; 709 participants from 2 studies; low-certainty evidence) or length of hospital stay (MD 0.1 respectively 0.2, 95% CI -0.68 to 1.08; data from 2 studies; moderate-certainty evidence). One trial (396 participants) compared MBP+oAB versus nBP. The evidence is uncertain about the effect of MBP+oAB on the incidence of SSI as well as mortality (RR 0.63, 95% CI 0.33 to 1.23 respectively RR 0.20, 95% CI 0.01 to 4.22; low-certainty evidence), while no effect on the risk of anastomotic leakages (RR 0.89, 95% CI 0.33 to 2.42; low-certainty evidence), the incidence of postoperative ileus (RR 1.18, 95% CI 0.77 to 1.81; low-certainty evidence) or the length of hospital stay (MD 0.1, 95% CI -0.8 to 1; low-certainty evidence) could be demonstrated. AUTHORS' CONCLUSIONS: Based on moderate-certainty evidence, our results suggest that MBP+oAB is probably more effective than MBP alone in preventing postoperative complications. In particular, with respect to our primary outcomes, SSI and anastomotic leakage, a lower incidence was demonstrated using MBP+oAB. Whether oAB alone is actually equivalent to MBP+oAB, or leads to a reduction or increase in the risk of postoperative complications, cannot be clarified in light of the low- to very low-certainty evidence. Similarly, it remains unclear whether omitting preoperative bowel preparation leads to an increase in the risk of postoperative complications due to limited evidence. Additional RCTs, particularly on the comparisons of MBP+oAB versus oAB alone or nBP, are needed to assess the impact of oAB alone or nBP compared with MBP+oAB on postoperative complications and to improve confidence in the estimated effect. In addition, RCTs focusing on subgroups (e.g. in relation to type and location of colon resections) or reporting side effects of the intervention are needed to determine the most effective approach of preoperative bowel preparation.

Surgical treatment for pancreatic cystic lesions-implications from the multi-center and prospective German StuDoQ|Pancreas registry.

PURPOSE: The 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. METHODS: Clinical 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. RESULTS: Patients 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. CONCLUSION: With 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.

[Recycling of Disposable Surgical Instruments - Is It Worth It?] / Recycling von chirurgischen Einweginstrumenten ­ lohnt sich das?

The German healthcare sector is responsible for 5.2% of the country's greenhouse gas emissions. One contributing factor is the enormous amount of waste generated daily in German hospitals, making them the fifth largest waste producer in Germany. Despite the potential for recycling, a significant portion of hospital waste is incinerated, as mandated by current regulations. This results in high levels of noxious CO2 emissions and the loss of valuable resources. The goal of this project was to demonstrate the feasibility of recycling complex, contaminated disposable surgical instruments.The study included frequently used disposable surgical instruments that could potentially be recycled as electronic waste. The instruments were wipe-disinfected and sterilised internally within the hospital. After sterilisation, the devices could be classified as electronic waste in consultation with the environmental authorities and then machine-recycled externally by a waste disposal company. Sorting machines shredded and separated the instruments into individual fractions of cables, plastics, different metals, and circuit boards, which were further processed into secondary raw materials.In the first six months (09/2022-03/2023), 239 kg of material were recycled instead of being incinerated. This resulted in a reduction of 545 kg CO2e. The metal content was estimated as 50% of the total weight; 30% were recyclable plastics, resulting in an 80% recycling rate. The ongoing recycling costs were 1.90 €/kg after deducting revenues. Thus, recycling in this model was approximately 3.9 times as expensive as incineration. A survey of the operating theatre personnel found high satisfaction with the recycling project and a minimal additional workload of less than five minutes.We demonstrated that recycling of contaminated disposable surgical instruments is possible in coordination with government authorities. This approach avoids waste incineration and leads to a reduction in CO2-equivalent emissions. However, the higher costs of recycling and the requirement for in-house decontamination pose limitations on the implementation of such projects. To address this, it is necessary for lawmakers to reconsider current regulations and involve manufacturers in recycling costs to fully exploit the enormous recycling potential.

Machine Learning for Decision-Support in Acute Abdominal Pain - Proof of Concept and Central Considerations.

Acute abdominal pain is a common presenting symptom in the emergency department and represents heterogeneous causes and diagnoses. There is often a decision to be made regarding emergency surgical care. Machine learning (ML) could be used here as a decision-support and relieve the time and personnel resource shortage.Patients with acute abdominal pain presenting to the Department of Surgery at Bonn University Hospital in 2020 and 2021 were retrospectively analyzed. Clinical parameters as well as laboratory values were used as predictors. After randomly splitting into a training and test data set (ratio 80 to 20), three ML algorithms were comparatively trained and validated. The entire procedure was repeated 20 times.A total of 1357 patients were identified and included in the analysis, with one in five (n = 276, 20.3%) requiring emergency abdominal surgery within 24 hours. Patients operated on were more likely to be male (p = 0.026), older (p = 0.006), had more gastrointestinal symptoms (nausea: p < 0.001, vomiting p < 0.001) as well as a more recent onset of pain (p < 0.001). Tenderness (p < 0.001) and guarding (p < 0.001) were more common in surgically treated patients and blood analyses showed increased inflammation levels (white blood cell count: p < 0.001, CRP: p < 0.001) and onset of organ dysfunction (creatinine: p < 0.014, quick p < 0.001). Of the three trained algorithms, the tree-based methods (h2o random forest and cforest) showed the best performance. The algorithms classified patients, i.e., predicted surgery, with a median AUC ROC of 0.81 and 0.79 and AUC PRC of 0.56 in test sets.A proof-of-concept was achieved with the development of an ML model for predicting timely surgical therapy for acute abdomen. The ML algorithm can be a valuable tool in decision-making. Especially in the context of heavily used medical resources, the algorithm can help to use these scarce resources more effectively. Technological progress, especially regarding artificial intelligence, increasingly enables evidence-based approaches in surgery but requires a strictly interdisciplinary approach. In the future, the use and handling of ML should be integrated into surgical training.

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.

Machine learning to guide clinical decision-making in abdominal surgery-a systematic literature review.

PURPOSE: An indication for surgical therapy includes balancing benefits against risk, which remains a key task in all surgical disciplines. Decisions are oftentimes based on clinical experience while guidelines lack evidence-based background. Various medical fields capitalized the application of machine learning (ML), and preliminary research suggests promising implications in surgeons' workflow. Hence, we evaluated ML's contemporary and possible future role in clinical decision-making (CDM) focusing on abdominal surgery. METHODS: Using the PICO framework, relevant keywords and research questions were identified. Following the PRISMA guidelines, a systemic search strategy in the PubMed database was conducted. Results were filtered by distinct criteria and selected articles were manually full text reviewed. RESULTS: Literature review revealed 4,396 articles, of which 47 matched the search criteria. The mean number of patients included was 55,843. A total of eight distinct ML techniques were evaluated whereas AUROC was applied by most authors for comparing ML predictions vs. conventional CDM routines. Most authors (N = 30/47, 63.8%) stated ML's superiority in the prediction of benefits and risks of surgery. The identification of highly relevant parameters to be integrated into algorithms allowing a more precise prognosis was emphasized as the main advantage of ML in CDM. CONCLUSIONS: A potential value of ML for surgical decision-making was demonstrated in several scientific articles. However, the low number of publications with only few collaborative studies between surgeons and computer scientists underpins the early phase of this highly promising field. Interdisciplinary research initiatives combining existing clinical datasets and emerging techniques of data processing may likely improve CDM in abdominal surgery in the future.

The rate of cholangiocarcinoma in Caroli Disease A German multicenter study.

BACKGROUND: Caroli Disease (CD) and Caroli Syndrome (CS) are rare disorders presenting with dilation of the intrahepatic bile ducts. CD/CS are associated with cholangiocarcinoma (CCA). However, the true incidence of CCA is still unclear, although it may serve as an indication for surgery. In this paper, we analyzed (I) the incidence of CCA in German centers, (II) reviewed our single center population together with its clinical presentation and (III) performed a thorough literature review. METHODS: 17 large HPB-centers across Germany were contacted and their patients after surgical treatment due to CD/CS with histopathology were included. Medline search for all studies published in English or German literature was performed. Patients who underwent surgery at our department between 2012 and 2020 due to CD or CS were analyzed. RESULTS: In the multicenter study, 79 patients suffered from CD and 119 patients from CS, with a total number of 198 patients. In 14 patients, CCA was found (Overall: 7,1%; CD: 6,3%, CS 7,6%). Between 2012 and 2020, 1661 liver resections were performed at our department. 14 patients underwent surgery due to CD or CS. Histological examination showed synchronous cholangiocarcinoma in one patient. The literature review revealed a CCA-rate of 7,3% in large series, whereas in case reports a rate of 6,8% was found. CONCLUSION: There is risk of malignant transformation and patients with CD might also benefit from resection due to improvement of symptoms. Therefore, resection is strongly advised. As certain patients with CS require transplantation, treatment should not be guided by the relatively low rate of CCA but by the concomitant diseases that come along with hepatic failure.

The Significance of Visceral Protection in Preventing Enteroatmospheric Fistulae During Open Abdomen Treatment in Patients With Secondary Peritonitis: A Propensity Score-matched Case-control Analysis.

OBJECTIVE: To evaluate the influence of a visceral protective layer (VPL) on the formation of enteroatmospheric fistulae (EAF) in open abdomen treatment (OAT) for peritonitis. BACKGROUND: EAF formation is a severe complication of OAT. Despite the widespread use of OAT, there are no robust evidence-based recommendations for preventing EAF. METHODS: A total of 120 peritonitis patients with secondary peritonitis as a result of a perforation of a hollow viscus or anastomotic insufficiency who had undergone OAT were included, and 14 clinical parameters were recorded in prospective OAT databases at 2 tertiary referral centers. For this analysis, patients with a VPL were assigned to the treatment group and those without a VPL to the control group. Propensity Score (PS) matching was performed. Known risk factors in OAT such as malignant disease, mortality, emergency operation, OAT duration, and fascial closure were matching variables. The influence of VPL on EAF formation was statistically evaluated using logistic regression analysis. RESULTS: With 34 patients in each group, no notable differences were identified with regard to age, sex, underlying disease, mortality, emergency operation, fascial closure, and OAT duration. Overall, a mortality rate of 22.1% for OAT due to peritonitis was observed. Mean OAT duration was approximately 9 days, and secondary fascial closure was achieved in more than two-thirds of all patients. Fascial traction was used in more than 75% of cases. EAF formation was significantly more frequent in the control group (EAF formation: VPL group 2.9% vs control 26.5%; P = 0.00). In the final regression analysis, the use of VPL resulted in a significant reduction in the risk of EAF formation (odds ratio 0.08; 95% confidence interval 0.01-0.71, P = 0.02), which translates to a relative risk reduction of 89.1%. CONCLUSION: VPL effectively prevents EAF formation during OAT in patients with peritonitis. We recommend the consistent use of VPL as part of a standardized OAT treatment algorithm.

Induction of cytotoxic effector cells towards cholangiocellular, pancreatic, and colorectal tumor cells by activation of the immune checkpoint CD40/CD40L on dendritic cells.

INTRODUCTION: Gastrointestinal (GI) malignancies, such as cholangiocarcinoma, pancreatic carcinoma, and metastatic colorectal carcinoma, have a poor prognosis and effective therapeutic approaches are still challenging. Checkpoint inhibition with PD-1 or PDL-1 antibodies revealed promising results in different tumor entities; however, only few patients with GI tumors can potentially benefit from PD1/PDL1 inhibiting immunotherapy. Further immunotherapeutic strategies for GI malignancies are urgently needed. The aim of this study was to demonstrate that in vitro activation of the immune checkpoint CD40/CD40L can improve DC action towards bile duct, pancreas, and colorectal carcinoma. METHODS: Human DC were isolated from buffy coats from healthy donors, pulsed with tumor lysates and then transduced with adenoviruses encoding human CD40L (Ad-hCD40L). Using transwell assays, the effects of (m)CD40L on DC immunoactivation compared to (s)CD40L were analyzed. Surface marker and cytokine/chemokine expression were measured by flow cytometry, ELISA and cytokine arrays. Capacity of Ad-hCD40L-transduced DC to induce tumor-specific effector cells was tested using MTT proliferation assay and cytotoxicity assays. Apoptosis induction on tumor cells after culturing with supernatants of Ad-hCD40L-transduced DC was analyzed by flow cytometry. RESULTS: Ad-hCD40L transduction induced a high expression of (s)CD40L and (m)CD40L on DC and seemed to induce a strong cellular CD40/CD40L interaction among DC, leading to the formation of cell aggregates. Due to the CD40/CD40L interaction, a significant upregulation of DC maturation markers and a Th1-shift on cytokines/chemokines in the supernatant of DC were achieved. Interestingly, a pure Th1-shift was only achieved, when a cellular CD40/CD40L interaction among DC took place. (s)CD40L induced almost no upregulation of maturation markers and rather resulted in a Th2-cytokine expression, such as IL-10. Correspondingly, (m)CD40L-expressing DC led to significant proliferation and stimulation of tumor-specific effector cells with increased cytotoxicity towards pancreatic, bile duct and colorectal tumor cells. Supernatants of Ad-hCD40L-transduced DC could also induce apoptosis in the different tumor cells in vitro. CONCLUSION: Stimulation of the immune checkpoint CD40L/CD40 by endogenous expression of (m)CD40L provokes a cellular interaction, which increases the immunomodulatory capacity of DC. A Th1 cytokine/chemokine expression is induced, leading to a significant proliferation and enabling cytotoxicity of effector cells towards human bile duct, pancreatic and colorectal tumor cells. The present data point to the promising approach for DC-based immunotherapy of gastrointestinal malignances by activating the CD40/CD40L immune checkpoint.

No evidence to support the impact of migration background on treatment response rates and cancer survival: a retrospective matched-pair analysis in Germany.

BACKGROUND: Immigration has taken the central stage in world politics, especially in the developed countries like Germany, where the continuous flow of immigrants has been well documented since 1960s. Strikingly, emerging data suggest that migrant patients have a poorer response to the treatment and lower survival rates in their new host country, raising concerns about health disparities. Herein, we present our investigation on the treatment response rate and cancer survival in German patients with and without an immigrant background that were treated at our comprehensive cancer center in Germany. METHODS: Initially, we considered 8162 cancer patients treated at the Center for Integrated Oncology (CIO), University Hospital Bonn, Germany (April 2002-December 2015) for matched-pair analysis. Subsequently, the German patients with a migration background and those from the native German population were manually identified and catalogued using a highly specific name-based algorithm. The clinical parameters such as demographic characteristics, tumor characteristics, defined staging criteria, and primary therapy were further adjusted. Using these stringent criteria, a total of 422 patients (n = 211, Germans with migration background; n = 211, native German population) were screened to compare for the treatment response and survival rates (i.e., 5-year overall survival, progression-free survival, and time to progression). RESULTS: Compared to the cohort with migration background, the cohort without migration background was slightly older (54.9 vs. 57.9 years) while having the same sex distribution (54.5% vs. 55.0% female) and longer follow-up time (36.9 vs. 42.6 months). We did not find significant differences in cancer survival (5-year overall survival, P = 0.771) and the response rates (Overall Remission Rate; McNemar's test, P = 0.346) between both collectives. CONCLUSION: Contrary to prior reports, we found no significant differences in cancer survival between German patients with immigrant background and native German patients. Nevertheless, the advanced treatment protocols implemented at our comprehensive cancer center may possibly account for the low variance in outcome. To conduct similar studies with a broader perspective, we propose that certain risk factors (country-of-origin-specific infections, dietary habits, epigenetics for chronic diseases etc.) should be considered, specially in the future studies that will recruit new arrivals from the 2015 German refugee crisis.

State-of-the-art colorectal disease: postoperative ileus.

PURPOSE: Postoperative Ileus (POI) remains an important complication for patients after abdominal surgery with an incidence of 10-27% representing an everyday issue for abdominal surgeons. It accounts for patients' discomfort, increased morbidity, prolonged hospital stays, and a high economic burden. This review outlines the current understanding of POI pathophysiology and focuses on preventive treatments that have proven to be effective or at least show promising effects. METHODS: Pathophysiology and recommendations for POI treatment are summarized on the basis of a selective literature review. RESULTS: While a lot of therapies have been researched over the past decades, many of them failed to prove successful in meta-analyses. To date, there is no evidence-based treatment once POI has manifested. In the era of enhanced recovery after surgery or fast track regimes, a few approaches show a beneficial effect in preventing POI: multimodal, opioid-sparing analgesia with placement of epidural catheters or transverse abdominis plane block; µ-opioid-receptor antagonists; and goal-directed fluid therapy and in general the use of minimally invasive surgery. CONCLUSION: The results of different studies are often contradictory, as a concise definition of POI and reliable surrogate endpoints are still absent. These will be needed to advance POI research and provide clinicians with consistent data to improve the treatment strategies.

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.

[Incidental finding of an intestinally differentiated adenocarcinoma in a tailgut cyst after robotic-assisted resection]. / Zufallsbefund eines intestinal differenzierten Adenokarzinoms in einer Tailgut Zyste nach robotisch-assistierter Resektion.

Due to pelvic symptoms, a diagnostic sectional imaging was initiated in a 52-year-old female patient. This revealed a cystic, retrorectal mass, suspected to be a tailgut cyst. Due to the symptoms and the unclear dignity after several frustrating endosonographic punctures, a robotic-assisted resection of the cystic Tumor was performed after careful interdisciplinary consultation.The histological examination confirmed the diagnosis of a tailgut cyst but also revealed parts of an intestinally differentiated adenocarcinoma.Due to the unclear metastatic behaviour, robotic-assisted low anterior resection with total mesorectal excision was performed as oncological resection, similar to rectal carcinomas. No residuals or lymph node metastases were detectable in the histological examination, so that follow- up monitoring was recommended.Retrorectal tumours are an extremely rare entity, worldwide only 28 cases of an intestinally differentiated carcinoma in a tailgut cyst have been described so far. Since there are no clear recommendations in the literature regarding the diagnostic or therapeutic procedure, we would like to discuss a possible algorithm in case of a proven retrorectal mass in our case study.

Active smokers show ameliorated delayed gastric emptying after pancreatoduodenectomy.

BACKGROUND: Delayed gastric emptying (DGE) is the most common complication following pancreatoduodenectomy (PD). The data about active smoking in relation to gastric motility have been inconsistent and specifically the effect of smoking on gastric emptying after PD has not yet been investigated in detail. METHODS: 295 patients at our department underwent PD between January 2009 and December 2019. Patients were analyzed in relation to demographic factors, diagnosis, pre-existing conditions, intraoperative characteristics, hospital stay, mortality and postoperative complications with special emphasis on DGE. All complications were classified according to the definitions of the International Study Group on Pancreatic Surgery. RESULTS: 274 patients were included in the study and analyzed regarding their smoking habits (non or former smokers, n = 88, 32.1% vs. active smokers, n = 186, 68.6%). Excluded were patients for whom no information about their smoking habits was available (n = 3), patients who had had gastric resection before (n = 4) and patients with prolonged postoperative resumption to normal diet independently from DGE (long-term ventilation > 7 days, fasting due to pancreatic fistula) (n = 14). Smokers were younger than non-smokers (61 vs. 69 years, p ≤ 0.001) and mainly male (73% male vs. 27% female). Smoking patients showed significantly more pre-existing pulmonary conditions (19% vs. 8%, p = 0.002) and alcohol abuse (48% vs. 23%, p ≤ 0.001). We observe more blood loss in smokers (800 [500-1237.5] vs. 600 [400-1000], p = 0.039), however administration of erythrocyte concentrates did not differ between both groups (0 [0-2] vs. 0 [0-2], p = 0.501). 58 out of 88 smokers (66%) and 147 out of 186 of non-smokers (79%) showed malign tumors (p = 0.019). 35 out of 88 active smokers (40%) and 98 out of 188 non- or former smokers (53%) developed DGE after surgery (p = 0.046) and smokers tolerated solid food intake more quickly than non-smokers (postoperative day (POD7 vs. POD10, p = 0.004). Active smokers were less at risk to develop DGE (p = 0.051) whereas patients with pulmonary preexisting conditions were at higher risk for developing DGE (p = 0.011). CONCLUSIONS: Our data show that DGE occurs less common in active smokers and they tolerate solid food intake more quickly than non-smokers. Further observation studies and randomized, controlled multicentre studies without the deleterious effect of smoking, for instance by administration of a nicotine patch, are needed to examine if this effect is due to nicotine administration.

[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.