Der Anteil alter Patienten in der Viszeralchirurgie wird in den nächsten Jahren immer weiter zunehmen. Alte Patienten haben nicht nur ein kalendarisch höheres Lebensalter: Sie weisen vielmehr typische Veränderungen der Physiologie und der funktionellen Reserve auf. Dieser Beitrag zeigt, wie man die erhöhte Vulnerabilität alter Patienten in der Viszeralchirurgie berücksichtigen kann.

Supplementary Data from Tumor-associated CD75s- and iso-CD75s-gangliosides are potential targets for adjuvant therapy in pancreatic cancer

Background Reconstruction after combined cardia resection and removal of the gastroesophageal junction can be carried out by the Merendino procedure or via a gastric conduit. This study compares postoperative complications and quality of life for both approaches. Methods All patients who underwent Merendino or gastric conduit reconstruction from 2011-2017 were included. Both groups were investigated regarding postoperative length of stay, complications, and gastrointestinal quality of life. Results 45 patients were identified, of which, 39 remained for analysis: 22 patients in the Merendino group and 17 patients in the gastric conduit group. The median age of patients in the gastric conduit group (71 (53-92) years) was significantly higher than in the Merendino group (58 (19-75) years), P = .0002. Hospital stay was significantly longer in the gastric conduit group (35.9 (11-82) days vs. 18.2 (7-43) days, P = .0299) and incidence of anastomotic leakage was higher (24% vs. 9%, P = .0171). General incidence of complications (Clavien-Dindo) did not vary (P = .1694). However, grade 5 complications only occurred in the Merendino group (n = 1). Evaluation of long-term outcome and quality of life showed dysphagia to only have occurred in the Merendino group (n = 3, 14%). Discussion Both approaches have advantages and disadvantages: The Merendino procedure showed reduced incidence of anastomotic leakage and shorter hospital stay but was associated with a higher in-hospital mortality rate. Discrepancies in subgroup populations as well as small patient numbers limit the interpretation of the findings. This study does however provide a first comparison of these surgical approaches and may serve as a basis for further investigation.

PURPOSE:Postoperative pancreatic fistula (POPF) with reported incidence rates up to 45% contributes substantially to overall morbidity. In this study, we conducted a retrospective evaluation of POPF along with its potential perioperative clinical risk factors and its effect on tumor recurrence. METHODS:Clinical data on patients who had received pancreatoduodenectomy (PD), distal pancreatectomy (DP), or duodenum-preserving pancreatic head resection (DPPHR) were prospectively collected between 2007 and 2016. A Picrosirius red staining score was developed to enable morphological classification of the resection margin of the pancreatic stump. The primary end point was the development of major complications. The secondary end points were overall and recurrence-free survival. RESULTS:340 patients underwent pancreatic resection including 222 (65.3%) PD, 87 (25.6%) DP, and 31 (9.1%) DPPHR. Postoperative major complications were observed in 74 patients (21.8%). In multivariable logistic regression analysis, POPF correlated with body mass index (BMI) (p = 0.025), prolonged stay in hospital (p<0.001), high Picrosirius red staining score (p = 0.049), and elevated postoperative levels of amylase or lipase in drain fluid (p≤0.001). Multivariable Cox regression analysis identified UICC stage (p<0.001), tumor differentiation (p<0.001), depth of invasion (p = 0.001), nodal invasion (p = 0.001), and the incidence of POPF grades B and C (p = 0.006) as independent prognostic markers of recurrence-free survival. CONCLUSION:Besides the known clinicopathological risk factors BMI and amylase in the drain fluid, the incidence of POPF correlates with high Picrosirius red staining score in the resection margins of the pancreatic stumps of curatively resected pancreatic ductal adenocarcinoma (PDAC). Furthermore, clinically relevant POPF seems to be a prognostic factor for tumor recurrence in PDAC.

Abstract Background Tracheo- or bronchoesophageal fistula (TBF) occurring after esophagectomy represent a rare but devastating complication. Management remains challenging and controversial. Therefore, the purpose of this study was to evaluate the outcome of different treatment approaches and to propose recommendations for the management of TBF. Methods From 2008 to 2018, 15 patients were treated because of TBF and were analyzed with respect to fistula appearance, treatment strategy (stenting, endoscopic vacuum therapy and/or surgical reintervention) and outcome. Results In each case, the fistula was small, located close to the tracheal bifurcation and associated simultaneously (n = 6, 40%) or metachronously (n = 9, 60%) with an anastomotic leakage. Latter was covered by esophageal stents in six patients which in turn resulted in occurrence of TBF at a later time in five patients. Management of TBF included conservative therapy (n = 3), stenting (n = 6), or suturing (n = 6). Ten patients underwent rethoracotomy. Treatment failure was observed in eight patients (53%). In all patients, treatment was accompanied by progressive sepsis. On the contrary, all seven patients with successful defect closure remained in good general condition. Conclusion Fistula appearance was similar in all patients. Implementation of esophageal stents cannot be recommended because of possibility of TBF at a later time point. Surgery is usually required and should preferably be performed when the patient's condition has been optimized at a single-stage repair. Esophageal diversion can only be recommended in patients with persisting mediastinitis. The key element for successful treatment of TBF, however, is control over sepsis; otherwise, outcome of TBF is devastating.

AIMS:The European Senior Program (ESP) aims to avoid waiting list competition between younger and elderly patients applying for renal transplantation. By listing patients ≥65 years on a separate waiting list and locally allocating of grafts ≥65 years exclusively to this cohort, waiting and cold ischemia times are predicted to be shortened, potentially resulting in improved kidney transplantation outcomes. This study compared a historic cohort of renal transplant recipients being simultaneously listed on the general and the ESP waiting lists with a collective exclusively listed on the ESP list in terms of surrogates of the transplantation outcome.METHODS:Total 151 eligible patients ≥ 65 years from Münster transplant Center, Germany, between 1999 and 2014 were included. Graft function, graft and patient survival were compared using surrogate markers of short- and long-term graft function. Patients were grouped according to their time of transplantation.RESULTS:Recipients and donors in the newESP (nESP) cohort were significantly older (69.6 ± 3.5 years vs 67.1 ± 2 years, p<0.05; 72.0 ± 5.0 years vs 70.3 ± 5.0 years, p = 0.039), had significantly shorter dialysis vintage (19.6 ± 21.7 months vs 60.2 ± 28.1 months, p<0.001) and suffered from significantly more comorbidities (2.2 ± 0.9 vs 1.8 ± 0.8, p = 0.009) than the historic cohort (HC). Five-year death-censored graft survival was better than in the HC, but 5-year graft and patient survival were better in the ESP cohort. After 2005, cold ischemia time between groups was comparable. nESP grafts showed more primary function and significantly better long-term graft function 18 months after transplantation and onwards.CONCLUSION:nESP recipients received significantly older grafts, but experienced significantly shorter time on dialysis. Cold ischemia times were comparable, but graft function in the nESP cohort was significantly better in the long term.

Background: Recurrent disease remains a major problem for esophageal cancer. This study was designed to evaluate the impact of localization of lymph node metastasis for tumor recurrence following curative esophageal resection. Methods: 273 patients undergoing esophagectomy for esophageal cancer between 2005 and 2014 at the Department of General, Visceral and Transplant Surgery, University Hospital of Münster were included. Tumor characteristics, treatment details, postoperative course and patients' outcome, including time point and localization of recurrent disease, were analyzed retrospectively. The median follow-up was 46.3 months. Results: Median overall and disease-free survivals were 22.7 and 13 months, respectively. Tumor characteristics including presence and number of lymph node metastasis, and localization of lymph node metastases, paraesophageal, perigastric and intra-abdominal, had significant impact on both tumor recurrence (p<0.001, p=0.003, and p=0.001, respectively) and disease-free survival (p<0.001, p=0.001, and p<0.001, respectively). Univariate and multivariate analysis confirmed tumor stage, lymph node metastasis, G-, L- and V-category, and neoadjuvant treatment as independent predictors of tumor recurrence. Conclusion: The tumor stage and response to neoadjuvant treatment remain the most important prognostic factors. In addition, localization and the number of resected lymph node metastasis can provide important additional information.

Aim: The present study aims to evaluate protective effects of a novel histidine-tryptophan-k etoglutarate solution (HTK-N) and to investigate positive impacts of an additional luminal preservation route in cold storage-induced injury on rat small bowels. Methods: Male Lewis rats were utilized as donors of small bowel grafts. Vascular or vascular plus luminal preservation were conducted with HTK or HTK-N and grafts were stored at 4 degrees C for 8 h followed by ex vivo warm oxygenated reperfusion with Krebs-Henseleit buffer for 30 min. Afterwards, intestinal tissue and portal vein effluent samples were collected for evaluation of morphological alterations, mucosal permeability and graft vitality. Results: The novel HTK-N decreased ultrastructural alterations but otherwise presented limited effect on protecting small bowel from ischemia-reperfusion injury in vascular route. However, the additional luminal preservation led to positive impacts on the integrity of intestinal mucosa and vitality of goblet cells. In addition, vascular plus luminal preservation route with HTK significantly protected the intestinal tissue from edema. Conclusion: HTK-N protected the intestinal mucosal structure and graft vitality as a luminal preservation solution. Additional luminal preservation route in cold storage was shown to be promising.

Pancreatic neuroendocrine neoplasms (pNENs) are rare, and their surgical management is complex. This study evaluated the current practice of pNEN surgery across Germany, including its adherence with guidelines and its perioperative outcomes. Patients who underwent surgery for pNENs (April 2013–June 2017) were retrieved from the prospective StuDoQ|Pancreas registry of the German Society of General and Visceral Surgery and retrospectively analyzed. A total of 287 patients (53.7% male) with a mean age of 59.2 ± 14.2 years old underwent pancreatic resection for pNENs. Tumors were localized in the pancreatic head (40.4%), body (23%), or tail (36.6%). A total of 239 (83.3%) patients underwent formal resection with lymphadenectomy, 40 (14%) parenchyma-sparing resection, and 8 (2.8%) only exploration. Fifty (17.4%) patients underwent a minimally invasive approach. Among the 245 patients with complete pathological information, 42 (17.1%) had distant metastases, 78 (31.8%) had stage I tumors, 74 (30.2%) stage II, and 51 (20.8%) stage III. A total of 112 (45.7%) patients had G1 tumors, 101 (41.2%) G2, and 24 (9.8%) G3. Nodal involvement on imaging was an independent predictor of lymph node metastasis according to the multivariable analysis (odds ratio: 0.057; 95% confidence interval: 0.016–0.209; p < 0.01). R0 resection was reported in 240 (83.6%) patients. The 30- and 90-day mortality rates were 2.8% and 4.2%, respectively. In Germany the rate of potential curative resection for pNEN is high. However, formal pancreatic resection seems to be overrepresented, while minimally invasive resection is underrepresented.

LAPTM4B is upregulated in a wide range of cancers associated with poor prognosis. However, the clinical impact of LAPTM4B as diagnostic and prognostic marker in pancreatic ductal adenocarcinoma (PDAC) remains unknown. Thus, the aim of the present study was to investigate the expression of LAPTM4B as circulating marker in PDAC. Expression analysis of LAPTM4B-35 in pancreatic tissue and preoperative blood serum samples of 169 patients with PDAC UICC Stages I–IV (n = 98), chronic pancreatitis (n = 41), and healthy controls (n = 30) by immunohistochemistry, Western blot, and ELISA. Descriptive and explorative statistical analyses of LAPTM4B-35’s potential as diagnostic and prognostic marker in PDAC. Expression of LAPTM4B-35 was significantly increased in tumor tissue and corresponding blood serum samples of patients with PDAC (each p < 0.001) and it could well discriminate PDAC from healthy controls and chronic pancreatitis (p < 0.001; p = 0.0037). LAPTM4B-35 in combination with CA.19-9 outperforms the diagnostic accuracy with an AUC of 0.903 (p < 0.001), sensitivity of 82%, and specificity of 92%. Kaplan–Meier survival analysis revealed an improved overall survival in PDAC UICC I–IV with low expression of circulating LAPTM4B-35 (17 versus 10 months, p = 0.039) as well as an improved relapse-free survival in curatively treated PDAC UICC I–III (16 versus 10 months; p = 0.037). Multivariate overall and recurrence-free survival analyses identified LAPTM4B-35 as favorable prognostic factor in PDAC patients (HR 2.73, p = 0.021; HR 3.29, p = 0.003). LAPTM4B-35 is significantly deregulated in PDAC with high diagnostic and prognostic impact as circulating tumor marker.

ENETS guidelines recommend parenchyma-sparing procedures without formal lymphadenectomy, ideally with a minimally invasive laparoscopic approach for sporadic small pNENs (≤2 cm). Non-functioning (NF) small pNENs can also be observed. The aim of the study was to evaluate how these recommendations are implemented in the German surgical community.

Objective: The total hepatic ischemia/reperfusion injury (IRI) involves the fact that both liver and gut are subjected to warm ischemia, which is a complex unavoidable process encountered during liver transplantation and a serious threat to graft outcome. The ways to improve hepatic IRI are currently limited. The aim of the present study was to explore the protective effect of simvastatin on total hepatic IRI and examine the underlying mechanisms. Methods: Male Sprague Dawley rats were subjected to total (100%) hepatic warm ischemia to induce hepatic IRI. Thirty-six male rats (250-300g) were randomly divided into three groups: sham, IRI control and simvastatin (1 mg/kg) pretreatment 0.5 h before surgery. Serum samples and liver tissues were collected after reperfusion at 6 and 24 h for further studies. Results: Simvastatin pretreatment significantly decreased the values of the transaminases alanine aminotransferase and aspartate aminotransferase and improved histological alterations according to improved Suzuki's Score (P< 0.05). Moreover, simvastatin upregulated the expression of Kruppel-like factor 2 (KLF2), phosphorylated endothelial nitric oxide synthase and thronnbonnodulin (P< 0.05). Furthermore, simvastatin pretreatment affected superoxide dismutase and malondialdehyde activities (P< 0.05) to reduce oxidative stress, and inhibited levels of high-mobility group box-1, CD68, toll-like receptor 4, tumor necrosis factor alpha, interleukin-1 beta and interleukin-6 (P<0.05) to suppress inflammatory response. Conclusion: Simvastatin pretreatment ameliorates total hepatic IRI via a KLF2-mediated protective mechanism. Simvastatin may be used as a potential prophylactic treatment strategy for clinical trials against hepatic IRI. (C) 2018 Elsevier Masson SAS. All rights reserved.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive carcinoma entities worldwide with early and rapid dissemination. Recently, we discussed the role of microRNAs as epigenetic regulators of Epithelial-to-Mesenchymal Transition (EMT) in PDAC. In this study, we investigated their value as diagnostic and prognostic markers in tissue and blood samples of 185 patients including PDAC, non-malignant pancreatic disorders, and age-matched healthy controls. Expression of the microRNA-200-family (microRNAs -141, -200a, -200b, -200c, -429) and microRNA-148a was significantly downregulated in tissue of PDAC Union internationale contre le cancer (UICC) Stage II. Correspondingly, stromal PDAC tissue showed strong expression of Fibronectin, Vimentin, and ZEB-1 (Zinc finger E-box-binding homeobox) versus low expression of E-cadherin. Transient transfection of microRNA-200b and microRNA-200c mimics resulted in the downregulation of their key target ZEB-1. Inversely, blood serum analyses of patients with PDAC UICC Stages II, III, and IV showed a significant over-expression of microRNA-200-family members, microRNA-148a, microRNA-10b, and microRNA-34a. Correspondingly, Enzyme-linked Immunosorbent Assay (ELISA) analyses revealed a significant over-expression of soluble E-cadherin in serum samples of PDAC patients versus healthy controls. The best diagnostic accuracy to distinguish between PDAC and non-PDAC in this patient collective could be achieved in tissue by microRNA-148a with an area under the receiver-operating-characteristic (ROC) curve (AUC) of 0.885 and in blood serum by a panel of microRNA-141, -200b, -200c, and CA.19-9 with an AUC of 0.890. Both diagnostic tools outreach the diagnostic performance of the currently most common diagnostic biomarker CA.19-9 (AUC of 0.834). Kaplan Meier survival analysis of this patient collective revealed an improved overall survival in PDAC patients with high expression of tissue-related microRNA-34a, -141, -200b, -200c, and -429. In conclusion, EMT-regulating microRNAs have great potential as liquid and solid biopsy markers in PDAC patients. Their prognostic and therapeutic benefits remain important tasks for future studies.

Recently, we identified the microRNA-99 family as unfavorable prognostic factor in patients with pancreatic ductal adenocarcinoma (PDAC). The aim of this study is to evaluate its value as circulating biomarker for PDAC.

Purpose Early treatment of pancreatic ductal adenocarcinoma (PDAC) is significantly delayed due to the lack of liquid biopsy markers for early diagnosis at surgically resectable tumor stages. Recent studies suggest that microRNA-205 (miR-205) is involved in PDAC progression by post-transcriptional regulation of epithelial-to-mesenchymal transition (EMT). However, the clinical potential of miR-205 as diagnostic and prognostic marker remains undefined and its exact role in PDAC is still ambiguous. This retrospective study is a substantial contribution to this on-going scientific discussion. Methods Expression analysis of miR-205 and its molecular targets in PDAC cell lines (n=5), human tissue (n=73), and blood serum samples (n=85) by qRT-PCR, tissue microarray immunohistochemistry, and western blot. Descriptive and explorative statistical analysis of miR-205's clinical potential for diagnosis and prognosis of PDAC. Results The expression of miR-205 differs more than 2000-fold (p<0.001) between epithelial and mesenchymal-like human PDAC cell lines correlating with EMT-marker expression of E-cadherin, vimentin, fibronectin, and ZEB-1. Expression of miR-205 is significantly upregulated in carcinoma tissue (eightfold, p=0.028) and serum (2.3-fold, p=0.023) of PDAC patients compared to age-matched healthy controls. In our patient collective circulating miR-205 in combination with CA.19-9 outperforms the diagnostic accuracy of CA.19-9 alone with an AUC of 0.890 (p<0.001), sensitivity of 0.867, and specificity of 0.933. Though non-significant, low expression of circulating miR-205 is more frequent in advanced tumor stages combined with a worse overall survival (6.9 vs. 11.9 months, p=0.176). Conclusion Besides its controversial role in carcinogenesis, miR-205 shows high potential as a solid and liquid biopsy marker in PDAC. This result is an urgent call for larger confirmatory multi-center studies.

BACKGROUND:The weekend effect describes a phenomenon whereby patients admitted to hospitals on weekends are at higher risk of complications compared to those admitted during weekdays. However, if a weekend effect exists in orthotopic liver transplantation (oLT).METHODS:We analyzed oLT between 2006 and 2016 and stratified patients into weekday (Monday to Friday) and weekend (Saturday, Sunday) groups. Primary outcome measures were one-year patient and graft survival.RESULTS:364 deceased donor livers were transplanted into 329 patients with 246 weekday (74.77%) and 83 weekend (25.23%) patients. Potential confounders (e.g. age, ischemia time, MELD score) were comparable. One-year patient and graft survival were similar. Frequencies of rejections, primary-non function or re-transplantation were not different. The day of transplantation was not associated with one-year patient and graft survival in multivariate analysis.CONCLUSIONS:We provide the first data for the Eurotransplant region on oLT stratified for weekend and weekday procedures and our findings suggest there was no weekend effect on oLT. While we hypothesize that the absent weekend effect is due to standardized transplant procedures and specialized multidisciplinary transplant teams, our results are encouraging showing oLT is a safe and successful procedure, independent from the day of the week.

BackgroundAccumulating evidence indicates that anastomotic leakages and perforations of the upper gastrointestinal tract (uGIT) can be treated successfully with endoscopic vacuum therapy (EVT). So far, no data is available regarding the long-term quality of life (QoL) after successful EVT of defects in the uGIT.MethodsWe present a prospective survey on long-term Qol of 52 patients treated by EVT for defects of the uGIT. Results are compared with 63 of 221 patients treated by esophagectomy without anastomotic insufficiency (w/o EVT) between 12/2011 and 12/2015. The Gastrointestinal Quality of Life-Index (GIQLI) score was determined by a 36-item questionnaire of 25 respondents with EVT and 50 respondents w/o EVT.ResultsThe response rate was 78.95% (75/95) including 25 survey respondents who were treated with EVT for anastomotic insufficiency secondary to esophagectomy or gastrectomy (n=19), iatrogenic esophageal perforation (n=4), and Boerhaave syndrome (n=2) and 50 respondents with complication-free esophagectomy w/o EVT. The median follow-up was 19months for EVT patients and 21months for patients w/o EVT. Except for social function (p=0.009) in favor for patients w/o EVT, the median GIQLI score did not differ significantly between both study groups concerning the categories symptoms', emotions', physical functions', and medical treatment' resulting in a total median GIQLI score of 83 in EVT versus 96.5 in patients w/o EVT (p=0.185). Spearman Rho analysis revealed that a high GIQLI score correlated with a low ASA score (p<0.001), a benign pathology (p=0.001), and a hospital stay less than 21days (p<0.001).ConclusionEVT in the uGIT is well tolerated by the patients and accompanied by a satisfactory long-term QoL.

OBJECTIVE: To investigate the effect of motion parameter feedback on laparoscopic basic skill acquisition and retention during a standardized box training curriculum.& para;& para;DESIGN: A Lap-X Hybrid laparoscopic simulator was designed to provide individual and continuous motion parameter feedback in a dry box trainer setting. In a prospective controlled trial, surgical novices were randomized into 2 groups (regular box group, n = 18, and Hybrid group, n = 18) to undergo an identical 5-day training program. In each group, 7 standardized tasks on laparoscopic basic skills were completed twice a day on 4 consecutive days in fixed pairs. Additionally, each participant performed a simulated standard laparoscopic cholecystectomy before (day 1) and after training (day 5) on a LAP Mentor II virtual reality (VR) trainer, allowing an independent control of skill progress in both groups. A follow-up assessment of skill retention was performed after 6 weeks with repetition of both the box tasks and VR cholecystectomy.& para;& para;SETTING: Muenster University Hospital Training Center, Muenster, Germany.& para;& para;PARTICIPANTS: Medical students without previous surgical experience.& para;& para;RESULTS: Laparoscopic skills in both groups improved significantly during the training period, measured by the overall task performance time. The 6 week follow-up showed comparable skill retention in both groups. Evaluation of the VR cholecystectomies demonstrated significant decrease of operation time (p < 0.01), path length of the left and right instrument, and the number of movements of the left and right instruments for the Hybrid group (all p < 0.001), compared to the box group. Similar results were found at the assessment of skill retention.& para;& para;CONCLUSION: Simulation training on both trainers enables reliable acquisition of laparoscopic basic skills. Furthermore, individual and continuous motion feedback improves laparoscopic skill enhancement significantly in several aspects. Thus, training systems with feedback of motion parameters should be considered to achieve long-term improvement of motion economy among surgical trainees. (C) 2017 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.

Background Bariatric surgery is the most efficient therapy for morbid obesity. Staple line and anastomotic leakage are the most feared postoperative complications after Roux-en-Y gastric bypass and laparoscopic sleeve gastrectomy (LSG). Traditional treatment options like revisional surgery and endoscopic stent placement are associated with high morbidity and mortality as well as variable success rates. Endoscopic vacuum therapy (EVT) has shown to be a new successful and feasible treatment option for leaks of different etiology after major gastro-esophageal surgery.Method We report a case of the EVT principle being applied in a patient with three major leaks located apart from each other within the gastric staple line after LSG for morbid obesity (BMI 62.7). EVT was initiated on postoperative day 8.Results In total, 18 endoscopic interventions were performed in 72 days, the vacuum sponge being replaced endoscopically every 4 days. Hospital length of stay was 106 days. No relevant procedure related complications were observed during the course of therapy and during the follow up.Conclusion EVT of postoperative leaks in the upper GI tract has been shown to be feasible and safe. It combines defect closure and effective drainage and allows a periodic inspection of the wound cavity. In case of therapeutic failure, it does not jeopardize surgical repair or stent placement. Even though the techniques and materials used in EVT still vary considerably according to local expertise, EVT has the potential to succeed as a nonsurgical, feasible, safe, and effective treatment option for postoperative leaks in bariatric surgery.