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Objective The aim of this study was to compare silicone-banded sleeve gastrectomy (BSG) to nonbanded sleeve gastrectomy (SG) regarding weight loss, obesity-related comorbidities, and complications. Summary background data As a primary bariatric procedure, SG leads to excellent weight loss, yet weight regain is a relevant issue in mid- to long-term follow-up. Retrospective analyses suggest that banding a sleeve using a silicone ring may decrease weight regain and improve weight loss. Methods The banded versus nonbanded sleeve gastrectomy single-center, randomized controlled trial was conducted from January 2015 to August 2019. The primary endpoint was defined as excess weight loss 3 years after surgery. Secondary endpoints included the surgery's impact on obesity-related comorbidities, quality of life, and complications. The study was registered under DRKS00007729. Results Among 94 patients randomized, 97% completed 3-year follow-up. Mean initial body mass index was 50.9 kg/m [95% confidence interval (CI), 49.6-52.2]. Mean adjusted excess weight loss 3 years after SG amounted to 62.3% (95% CI, 56.2-68.5) and 73.9% ( 95% CI, 67.8-80.0) after BSG (difference 11.6%, P = 0.0073). Remission of type 2 diabetes occurred in 66.7% (4/6) after SG and in 91.0% (10/11) following BSG (P = 0.21). Three years after surgery, ring implantation correlated with decreased frequency of symptomatic reflux episodes (P = 0.01) but increased frequency of regurgitation (P = 0.03). The rate of major complications was not different between the study groups (BSG, n = 3; SG, n = 2; P = 0.63). Quality of life was better following BSG (P = 0.001). Conclusions BSG provided better weight loss than nonbanded SG 3 years after surgery. Regurgitation was the main clinically relevant negative effect after BSG.

Background In 2017, the prevalence of obesity (BMI ≥ 30 kg/m2) in Germany was approximately 16%. Obesity increases an individual's risk of developing type 2 diabetes (T2DM) and arterial hypertension; it also increases overall mortality. Consequently, effective treatment is a necessity. Approximately 20 000 bariatric operations are performed in Germany each year. Methods This review is based on pertinent publications retrieved by a selective search in the PubMed and Cochrane databases and on current German clinical practice guidelines. Results The types of obesity surgery most commonly performed in Germany, Roux-en-Y gastric bypass and sleeve gastrectomy, lead to an excess weight loss of 27-69% ≥ 10 years after the procedure. In obese patients with T2DM, the diabetes remission rate ≥ 10 years after these procedures ranges from 25% to 62%. Adjusted regression analyses of data from large registries have shown that the incidence of malignancies is 33% lower in persons who have undergone obesity surgery compared to control subjects with obesity (unadjusted incidence 5.6 versus 9.0 cases per 1000 person-years). The operation can cause vitamin deficiency, surgical complications, gastroesophageal reflux, and dumping syndrome. Therefore, lifelong follow-up is necessary. Conclusion In view of an increasing number of patients undergoing bariatric surgery, it will probably not be feasible in the future for lifelong follow-up to be provided exclusively in specialized centers.

Background Laparoscopic sleeve gastrectomy (SG) achieves excellent weight loss, yet recent reports indicate weight regain in a substantial number of patients. Objectives Inserting a nonadjustable gastric band may improve weight loss after SG. Setting University Hospital, Germany. Methods In a retrospective matched-pair analysis 51 patients who underwent banded SG (BSG) using a silicone ring between November 2010 and May 2017 were compared with patients who underwent conventional SG regarding weight loss, complications, and co-morbidity. Median follow-up was 5 years. Results Total weight loss was equal in the early follow-up (P = .118 and P = .111) but significantly better in BSG 3 and 5 years after surgery (BSG versus SG at 3 yr 38.7% ± 7.8, n = 33 versus 31.9 ± 10.7, n = 33, P = .002; BSG versus SG at 5 yr 37.6% ± 8.5, n = 27 versus 29.5 ± 12.9, n = 23, P = .008). Ring placement had no significant impact on clinical reflux signs (Fisher's exact test P > .999), yet 37 % of BSG patients reported ≥1 regurgitation per week (Fisher's exact test P = .013, odds ratio 12.4). Conclusion BSG leads to better weight loss than nonbanded SG 5 years after surgery. This comes at the expense of a higher rate of regurgitation. At a time in which weight loss limitations of a stand-alone SG are becoming a clinical problem, banding the sleeve may be a strategy to improve weight loss with this procedure.

The hindgut theory hypothesizes a key role of differential hindgut stimulation following metabolic procedures in ameliorating diabetes mellitus. We used two strategies to remove the hindgut from intestinal continuity in order to analyze its impact on diabetes mellitus. Loop duodeno-jejunostomy (DJOS) with exclusion of one-third of total intestinal length was performed in 3 groups of 9-week-old Zucker diabetic fatty rats. In group 1, no further alteration of the intestinal tract was made. Group 2 received additional ileal exclusion (IE). Group 3 underwent additional resection of 50% of the ileum with side-to-side ileocecal anastomosis (IR). One, 2, and 4 months after surgery, fasting blood glucose levels, oral glucose tolerance tests (OGTT), and glucose-stimulated hormone analyses were conducted, and bile acid blood levels were compared. Body weight was documented weekly. In relation to DJOS, glucose control was not impaired in IR or IE. On the contrary, only IR could maintain preOP glucose values until 4 months. There were no significant weight differences between the groups. Confirming effective ileal diversion, bile acid blood levels were significantly higher in the DJOS group compared with both IR and IE (p = 0.0025 and p = 0.0047). Operative interventions had no impact on GLP-1 levels at any time point (ANOVA p > 0.05 for all). Insulin secretion was preserved in all groups. This data supports the hypothesis that the mechanisms driving amelioration of diabetes mellitus are complex and cannot be reduced to the ileum.

Background Bio‐absorbable sealants are widely used to reduce the rate and severity of postoperative pancreatic fistulas after distal pancreatectomy. However, numerous clinical trials have failed to demonstrate their clinical benefit. We therefore investigated stability and bio‐compatibility of absorbable sealants in vitro and in vivo. Methods In vitro, polymerized compounds were incubated in pancreatic juice before their stability was tested. In vivo, two compounds were used to seal the pancreatic stump after distal pancreatectomy in nine pigs. Burst pressure of the pancreatic stump, surgical outcome, histology of the pancreatic stump, systemic inflammation, and drain fluid was examined. Results Products based on fibrin or collagen were unstable in the presence of active pancreatic enzymes and completely dissolved within 2 h. Sealants using chemical cross‐linking of proteins showed improved stability for 7 days. In vivo, application of polyethylenglycol‐based sealant leads to complete closure of the pancreatic duct after 5 days, while a glutaraldehyde‐based sealant prevented physiological closure of the pancreatic main duct. Conclusions Many compounds used clinically to reinforce the pancreatic stump after distal pancreatectomy are inadequate due to instability in the presence of pancreatic enzymes. While selected bio‐absorbable sealants inhibited the natural healing of the pancreatic stump, polyethylenglycol‐based sealants should be tested in further clinical trials.

Introduction: Lipoedema is characterized as subcutaneous lipohypertrophy in association with soft-tissue pain affecting female patients. Recently, the disease has undergone a paradigm shift departing from historic reiterations of defining lipoedema in terms of classic edema paired with the notion of weight loss-resistant leg volume towards an evidence-based, patient-centered approach. Although lipoedema is strongly associated with obesity, the effect of bariatric surgery on thigh volume and weight loss has not been explored. Material and Methods: In a retrospective cohort study, thigh volume and weight loss of 31 patients with lipoedema were analyzed before and 10–18 and ≥19 months after sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB). Fourteen patients, with distal leg lymphoedema (i.e., with healthy thighs), who had undergone bariatric surgery served as controls. Statistical analysis was performed using a linear mixed-effects model adjusted for patient age and initial BMI. Results: Adjusted initial thigh volume in patients with lipoedema was 23,785.4 mL (95% confidence interval [CI] 22,316.6–25,254.1). Thigh volumes decreased significantly in lipoedema and control patients (baseline vs. 1st follow-up, p < 0.0001 and p = 0.0001; baseline vs. 2nd follow-up, p < 0.0001 and p = 0.0013). Adjusted thigh volume reduction amounted to 33.4 and 37.0% in the lipoedema and control groups at the 1st follow-up, and 30.4 and 34.7% at the 2nd follow-up, respectively (lipoedema vs. control p > 0.999 for both). SG and RYGB led to an equal reduction in leg volume (operation type × time, p = 0.83). Volume reduction was equally effective in obese and superobese patients (weight category × time, p = 0.43). Conclusion: SG and RYGB lead to a significant thigh volume reduction in patients with lipoedema.

Objective To examine pasireotide’s effect on intestinal anastomotic healing under physiological conditions and following preoperative whole-body irradiation. Material and methods Forty-five male Wistar rats received an ileoileal end-to-end anastomosis. Group 1 (Co, n = 9) served as control. Group 2 (SOM, n = 10) received pasireotide (60 mg/kg) 6 days preoperatively. Group 3 (R-Co, n = 13) was subjected to 8 Gy whole-body irradiation 4 days preoperatively. Finally, group 4 (R-SOM, n = 13) received pasireotide 6 days preoperatively and whole-body irradiation 4 days preoperatively. On postoperative day 4, anastomotic bursting pressure, histology, IGF-1 staining, and collagen density were examined. Results Mortality was higher in irradiated animals (30.8% vs. 5.3%, p = 0.021), and anastomotic bursting pressure was significantly lower (median, R-Co = 83 mmHg; R-SOM = 101 mmHg; Co = 149.5 mmHg; SOM = 169 mmHg). Inflammation measured by leukocyte infiltration following irradiation was reduced (p = 0.023), and less collagen was observed, though this was not statistically significant. Bursting pressure did not significantly differ between Co and SOM and between R-Co and R-SOM animals respectively. Semi-quantitative scoring of IGF-1, fibroblast bridging, or collagen density did not reveal significant differences among the groups. Conclusion Whole-body irradiation decreases the quality of intestinal anastomotic wound healing and increases mortality. Pasireotide does not significantly lessen this detrimental effect.

Die chirurgische Therapie der Adipositas in Deutschland ist ein sich rasch entwickelndes Gebiet, welches streng an die Nationalen Leitlinien gebunden ist. Darstellung der Belastung der Adipositaszentren durch den exponentiellen Anstieg postbariatrischer Patienten In einer retrospektiven Studie haben wir deskriptiv die Entwicklung der ambulanten Patientenzahlen an unserem universitaren Adipositaszentrum (gegrundet 2007) untersucht. Die Patientenbesuche wurden jahrlich ausgewertet und in zwei Gruppen eingeteilt: Erstvorstellung und Wiedervorstellung. Die Anzahl der durchgefuhrten bariatrischen Operationen sowie deren Akzeptanz/Kostenubernahme durch die Krankenkassen wurden ebenfalls evaluiert. Im Jahr 2007 wurden insgesamt 318 Patienten gesehen: 156 waren Erstvorstellungen, 162 Wiedervorstellungen. Die Ablehnungsrate der Kostenubernahme durch die Krankenkassen betrug 16,8 %. 2016 gab es 1691 Patientenvorstellungen (2016 vs. 2007 + 532 %), hiervon 487 Erstvorstellungen (+312 %) und 1204 Wiedervorstellungen (+743 %). Die Ablehnungsrate seitens der Krankenkassen fiel auf 1,8 %, wahrend sich die Anzahl der Operationen nahezu verzehnfachte. Mit der steigenden Akzeptanz der bariatrischen Therapie muss sich eine vergleichsweise kleine Zahl an spezialisierten Zentren mit der exponentiell steigenden Nachsorgefrequenz auseinandersetzen. In Anbetracht des Ausmases der Adipositasepidemie stellt insbesondere eine adaquate Nachsorge ein soziookonomisches Problem dar, welches nur im interdisziplinaren Setting unter struktureller Integration in das komplexe Gesundheitssystem gelost werden kann.

There is an ongoing debate on which procedure provides the best treatment for type 2 diabetes. Furthermore, the pathomechanisms of diabetes improvement of partly anatomically differing operations is not fully understood. A loop duodenojejunostomy (DJOS) with exclusion of one third of intestinal length, a sleeve gastrectomy (SG), or a combination of DJOS + SG was performed in 8-week-old male ZDF rats. One, three, and six months after surgery, an oral glucose tolerance test and measurements of GLP-1, GIP, insulin, and bile acids were conducted. After an initial (4 weeks) equal glucose control, DJOS and DJOS + SG showed significantly lower glucose levels than SG 3 and 6 months after surgery. There was sharp decline of insulin levels in SG animals over time, whereas insulin levels in DJOS and DJOS + SG were preserved. GIP levels were significantly larger in both groups containing a sleeve at all three time points, whereas GLP-1 was equal in all groups at all time. Bile acid levels were significantly higher in the DJOS compared to the SG group at all time points. Interestingly, the additional SG in the DJOS + SG group led to lower bile acid levels 1 and 6 months postoperatively. The effect of SG on glucose control was transient, whereas a duodenal exclusion was the more effective procedure in this model due to a sustained pancreatic function with a preserved insulin secretion.

Metabolic surgery is known to impact glucose tolerance but the exact mechanism is still unclear. Based on recently-published data, especially the role of the hindgut may require redefinition.Either a loop duodeno-jejunostomy (DJOS) with exclusion of one third of total intestinal length, a loop duodeno-ileostomy (DiOS, exclusion of two thirds), or SHAM operation was performed in 9-week-old Zucker diabetic fatty rats. One, 3, and 6 months after surgery, an oral glucose tolerance test (OGTT) and glucose-stimulated hormone analyses were conducted. Body weight was documented weekly.DJOS and DiOS animals showed significantly better glucose control in all OGTTs than the SHAM group (two-way ANOVA p 0.0001). Body weight developed largely parallel in both intervention groups; SHAM animals had gained significantly less weight after 6 months (Mann-Whitney DJOS/DiOS vs. SHAM p 0.05, DJOS vs. DiOS p 0.05). Operative interventions had no impact on GLP-1 and GIP levels at any time point (Mann-Whitney p 0.05 for all). DJOS/DiOS operations could preserve insulin production up to 6 months, while there was already a sharp decline of insulin levels in the SHAM group (Mann-Whitney: DJOS/DiOS vs. SHAM p 0.05 for all time points). Additionally, insulin sensitivity was improved significantly 1 month postoperative in both intervention groups compared to SHAM (Mann-Whitney DJOS/DiOS vs. SHAM p 0.05).The data of the current study demonstrate a sharp amelioration of glucose control after duodenal exclusion with unchanged levels of GLP-1 and GIP. Direct or delayed hindgut stimulation had no impact on glucose control in our model.

Background Intestinal anastomotic insufficiency (AI) is a common problem in visceral surgery associated with overexpression of matrix metalloproteinases (MMPs). In some patients it occurs more than once. The etiology of recurring anastomotic insufficiency (RAI) is not understood yet and should be addressed as an independent disease entity. Materials and methods Thirty nine consecutive patients with AI were treated at our university center and were included in this prospective study. Clinical data were evaluated by correlative statistical analysis to identify independent risk factors for RAI. Patients were divided in two groups: 18 patients had a single operative revision until restoration (group SAI), and 21 patients had two or more revisions (group RAI). Anastomotic tissue samples as well as untouched bowel wall were collected during reoperations for analysis of MMPs and tissue inhibitor of metalloproteinases (TIMP2). Clinical data were correlated with pathological observations. Results Significant differences of clinical and molecular pathological data were found between the two groups. Transfusion of red blood cells until the first reoperation and alcohol abuse led to RAI and were the only independent risk factors for RAI in multivariate analysis. Overexpression of MMP-8, -9, and -13 in anastomotic tissue correlated with the administration of red blood cells during initial operation. Reduced expression of TIMP2 was frequent in nearly all patients without differences throughout the subgroups. Conclusions RAI seems to have an independent disease pattern. Transfusion of blood products is not only a known risk factor for AI but seems to significantly disturb the anastomotic healing process leading to RAI.

Bariatrische Operationen werden in Deutschland immer haufiger durchgefuhrt. Primareingriffe werden meist in spezialisierten Zentren durchgefuhrt. Es gibt jedoch spate Komplikationen, die Monate bis Jahre nach der Operation auftreten und mit denen jeder Allgemein- und Viszeralchirurg, unabhangig von der Grose und Spezialisierung seiner Klinik, konfrontiert werden kann. Der laparoskopische Roux-Y-Magenbypass ist weltweit die am haufigsten durchgefuhrte bariatrische Operation. Durch das antekolische Hochfuhren der alimentaren Schlinge zum Pouch entsteht dorsal der alimentaren Schlinge und unterhalb des Kolon transversum eine Mesenteriallucke, auch Petersen-Lucke genannt. Sowohl hier als auch im Bereich der Mesenteriallucke der Roux-Anastomose kann es zu einer inneren Hernie kommen, d. h. der Dunndarm kann sich hier um die eigene Achse drehen. Abdominelle Beschwerden durch Darmobstruktion sind unspezifisch, aber sehr ausgepragt. Patienten prasentieren klinisch entweder ein akutes Abdomen oder intermittierende abdominelle, unspezifische Schmerzen mit Ubelkeit und selten auch Erbrechen. Meistens zeigen die klinischen und die laborchemischen Untersuchungen keinen wegweisenden Befund. Im Zweifel bildet daher die kontrastmittelverstarkte Computertomografie des Abdomens die bildgebende Diagnostik der Wahl. Eine diagnostische Laparoskopie sollte bei jedem Patienten mit klinischem Verdacht auf eine innere Hernie auch bei unauffalligem CT erfolgen. Die diagnostische Laparoskopie sollte durch einen laparoskopisch versierten Operateur mit Erfahrung in der bariatrischen Chirurgie durchgefuhrt werden, da ohne genaue Kenntnis der Bruchpforten die Zuordnung der Darmschlingen sehr schwierig ist. Der primare Blick geht nach inframesokolisch unter Hochheben des Kolon transversum. Von hier aus bietet sich bei offener Petersen-Lucke die direkte Sicht von rechts auf das Treitz-Band. Falls man rechts davon Dunndarm vorfindet, besteht eine Petersen-Hernie. Nach dem inframesokolischen Blick sollte man die Gastroenterostomie aufsuchen und sich entlang der alimentaren Schlinge nach distal in Richtung Jejunojejunostomie vorarbeiten. Dort findet man die 2. mogliche Lucke. Nachdem beide Lucken aufgefunden und ggf. eine Hernie reponiert werden konnte, sollten die Lucken mit einer nicht resorbierbaren Naht verschlossen werden.

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease. Circulating tumor cells (CTC) in the blood are hypothesized as the means of systemic tumor spread. Blood obtained from healthy donors and patients with PDAC was therefore subject to size-based CTC-isolation. We additionally compared Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations in pancreatic CTC and corresponding tumors, and evaluated their significance as prognostic markers. Samples from 68 individuals (58 PDAC patients, 10 healthy donors) were analyzed; CTCs were present in patients with UICC stage IA-IV tumors and none of the controls (p 0.001). Patients with3 CTC/ml had a trend for worse median overall survival (OS) than patients with 0.3–3 CTC/ml (P = 0.12). Surprisingly, CTCs harbored various KRAS mutations in codon 12 and 13. Patients with a KRAS G12V mutation in their CTC (n = 14) had a trend to better median OS (24.5 months) compared to patients with other (10 months), or no detectable KRAS mutations (8 months; P = 0.04). KRAS mutations in CTC and corresponding tumor were discordant in 11 of 26 “tumor-CTC-pairs” (42%), while 15 (58%) had a matching mutation; survival was similar in both groups (P = 0.36). Genetic characterization, including mutations such as KRAS, may prove useful for prognosis and understanding of tumor biology.

Laparoscopic sleeve gastrectomy (LSG) can achieve excellent weight loss, yet sleeve dilatation with concomitant weight regain proves to be a relevant issue. Hence, additional restriction might improve results after LSG. In a retrospective matched-pair analysis, 42 patients who underwent banded LSG (BLSG) using a MiniMizer® ring between January 2012 and October 2014 were analysed regarding weight loss, complications and comorbidity. Median follow-up was 3 years. Forty-two patients who had undergone conventional LSG were selected as matched pairs. Mean preoperative BMI was 54.93 ± 7.42 kg/m2 for BLSG and 53.46 ± 6.69 kg/m2 for LSG (Mann-Whitney P = 0.540). Total weight loss (%TWL) was significantly greater in the BLSG group 3 years after surgery (BLSG 38.22% ± 7.26; n = 26 vs. LSG 32.69 ± 9.47; n = 26; P = 0.0154). Ring placement had no relevant impact on new-onset reflux (Fisher’s exact test P = 1.0) but a tendency towards reflux improvement when reflux pre-existed (odds ratio 1.96). The major side effect of ring implantation was regurgitation with over 44% of patients presenting with regurgitation >1 per week (Fisher’s exact test P = 0.0019, odds ratio 18.07). BLSG is a safe procedure showing similar comorbidity to conventional LSG. However, BLSG leads to a higher rate of postoperative regurgitation. Weight loss is significantly improved 3 years after surgery. Hence, additional ring implantation might be an option for increased restriction in LSG surgery.

Pancreatoduodenectomy is the most common operative procedure performed for distal bile duct carcinoma. Data on outcome after surgery for this rare malignancy is scarce, especially from western countries. The purpose of this study is to explore the prognostic factors and outcome after pancreatoduodenectomy for distal bile duct carcinoma. Patients receiving pancreatoduodenectomy for distal bile duct carcinoma were identified from institutional databases of five German and one Russian academic centers for pancreatic surgery. Univariable and multivariable general linear model, Kaplan-Meier method, and Cox regression were used to identify prognostic factors for postoperative mortality and overall survival. N = 228 patients operated from 1994 to 2015 were included. Reoperation (OR 5.38, 95%CI 1.51–19.22, p = 0.010), grade B/C postpancreatectomy hemorrhage (OR 3.73, 95%CI 1.13–12.35, p = 0.031), grade B/C postoperative pancreatic fistula (OR 4.29, 95%CI 1.25–14.72, p = 0.038), and advanced age (OR 4.00, 95%CI 1.12–14.03, p = 0.033) were independent risk factors for in-hospital mortality in multivariable analysis. Median survival was 29 months, 5-year survival 27%. Positive resection margin (HR 2.07, 95%CI 1.29–3.33, p = 0.003), high tumor grade (HR 1.71, 95%CI 1.13–2.58, p = 0.010), lymph node (HR 1.68, 95%CI 1.13–2.51, p = 0.011), and distant metastases (HR 2.70, 95%CI 1.21–5.58, p = 0.014), as well as severe non-fatal postoperative complications (HR 1.64, 95%CI 1.04–2.58, p = 0.033) were independent negative prognostic factors for survival in multivariable analysis. Distant metastases and positive resection margin are the strongest negative prognostic factors for survival after pancreatoduodenectomy for distal bile duct carcinoma; thus, surgery with curative intent is only warranted in patients with local disease, where R0 resection is feasible.

To investigate the limited benefit of antibiotics in ameliorating the outcome of acute necrotizing pancreatitis, we analyzed antibiotic therapy in primarily infected necrotizing pancreatitis in mice with respect to the local pancreatic pathology as well as systemic, pancreatitis induced adverse events.Sterile pancreatic necrosis (SN) was induced by retrograde injection of 4% taurocholate in the common bile duct of Balb/c mice. Primarily infected pancreatic necrosis (IN) was induced by co-injecting 10(8) CFU/ml Escherichia coli. 10 mg/kg of moxifloxacin was administered prior to pancreatitis induction (AN). After 24 h, animals were sacrificed to examine serum as well as organs for signs of SIRS.Moxifloxacin significantly reduced bacterial count in pancreatic lysates of animals with infected pancreatic necrosis (IN 4.1·10(7) ± 2.4·10(7) vs. AN 4.9·10(4) ± 2.6·10(4) CFU/g; p 0.001). However, it did not alter pancreatic histology or pulmonary damage (Histology score: IN 23.8 ± 2.7 vs. AN 22.6 ± 1.7). Moxifloxacin reduced systemic immunoactivation (Serum IL-6: IN 330.5 ± 336.6 vs. 38.7 ± 25.5 pg/ml; p 0.001), hypoglycemia (serum glucose: IN 105.8 ± 12.7 vs. AN 155.7 ± 39.5 mg/dl; p 0.001), and serum aspartate aminotransferase (IN 606 ± 89.7 vs. AN 255 ± 52.1; p 0.05). These parameters were significantly increased in animals with necrotizing pancreatitis.In the experimental setting, initial antibiotic therapy with moxifloxacin in acute infected necrotizing pancreatitis in mice does not have a beneficial impact on pancreatic pathology or pulmonary damage. However, other systemic complications induced by infected necrosis in acute pancreatitis are reduced by the administration of moxifloxacin.

Clinical data indicate that laparoscopic surgery has a beneficial effect on intestinal wound healing and is associated with a lower incidence of anastomotic leakage. This observation is based on weak evidence, and little is known about the impact of intraoperative parameters during laparoscopic surgery, e.g., temperature and humidity.A small-bowel anastomosis was formed in rats inside an incubator, in an environment of stable humidity and temperature. Three groups of ten Wistar rats were operated: a control group (G1) in an open surgical environment and two groups (G2 and G3) in the incubator at a humidity of 60 % and a temperature of 30 and 37 °C (G2 and G3, respectively). After 4 days, bursting pressure and hydroxyproline concentration of the anastomosis were analyzed. The tissue was histologically examined. Serum levels of C-reactive-protein (CRP) were measured.No significant changes were seen in the evaluation of anastomotic stability. Bursting pressure was very similar among the groups. Hydroxyproline concentration in G3 (36.3 μg/g) was lower by trend (p = 0.072) than in G1 (51.7 μg/g) and G2 (46.4 μg/g). The histological evaluation showed similar results regarding necrosis, inflammatory cells, edema, and epithelization for all groups. G3 (2.56) showed a distinctly worse score for submucosal bridging (p = 0.061) than G1 (1.68). A highly significant increase (p = 0.008) in CRP was detected in G3 (598.96 ng/ml) compared to G1 (439.49 ng/ml) and G2 (460 ng/ml).A combination of high temperature and humidity during surgery induces an increased systemic inflammatory response and seems to be attenuating the early regeneration process in the anastomotic tissue.

OBJECTIVE Infection of pancreatic necrosis in necrotizing pancreatitis increases the lethality of patients with acute pancreatitis. To examine mechanisms underlying this clinical observation, we developed and tested a model, in which primary infection of necrosis is achieved in taurocholate-induced pancreatitis in mice. METHODS Sterile necrosis of acute necrotizing pancreatitis was induced by retrograde injection of 4% taurocholate into the common bile duct of Balb/c mice. Primary infection of pancreatic necrosis was induced by coinjecting 10 colony-forming units of Escherichia coli. Animals were killed after 6, 12, 24, 48, and 120 hours, and pancreatic damage and pancreatitis-associated systemic inflammatory response were assessed. RESULTS Mice with pancreatic acinar cell necrosis had an increased bacterial concentration in all tissues and showed sustained bacteremia. Acute pancreatitis was induced only by coinjection of taurocholate and not by bacterial infection alone. Infection of pancreatic necrosis increased pancreatic damage and the pulmonary vascular leak. Serum glucose concentrations serving as a parameter of hepatic function were reduced in mice with infected pancreatic necrosis. CONCLUSIONS Primary infection of pancreatic necrosis with E. coli increases both pancreatic damage and pulmonary and hepatic complications in acute necrotizing pancreatitis in mice.

It has been shown that crystalloid fluid-overload promotes anastomotic instability. As physiologic anastomotic healing requires the sequential infiltration of different cells, we hypothesized this to be altered by liberal fluid regimes and performed a histomorphological analysis.36 Wistar rats were randomized into 4 groups (n=8-10 rats/group) and treated with either liberal (+) or restrictive (-) perioperative crystalline (Jonosteril = Cry) or colloidal fluid (Voluven = Col). Anastomotic samples were obtained on postoperative day 4, routinely stained and histophathologically reviewed. Anastomotic healing was assessed using a semiquantitative score, assessing inflammatory cells, anastomotic repair and collagenase activity.Overall, the crystalloid overload group (Cry (+)) showed the worst healing score (P0.01). A substantial increase of lymphocytes and macrophages was found in this group compared to the other three (P0.01). Both groups that received colloidal fluid (Col (+) and Col (-)) as well as the group that received restricted crystalloid fluid resuscitation (Cry (-)) had better intestinal healing. Collagenase activity was significantly higher in the Cry (+) group.Intraoperative infusion of high-volume crystalloid fluid leads to a pathological anastomotic inflammatory response with a marked infiltration of leukocytes and macrophages resulting in accelerated collagenolysis.

Acute necrotizing pancreatitis (NAP) induces a systemic inflammatory response syndrome. We investigated the underlying changes of monocytes using different activation markers.A retrograde injection of 2 mL/kg bodyweight of sodium taurocholate into the common bile duct of BALB/c mice induced NAP, whereas sham-operated animals (SOP) were treated with saline. After 6, 12, 24, and 48 h, histologic alterations, pancreatic enzymes, and interleukin 6 in serum, albumin, and myeloperoxidase (MPO) in bronchoalveolar lavage fluid were examined. Isolation of mononuclear cells from the blood, spleen, and liver and the subsequent determination of macrophages (F4/80) and their activation marker CD121b and MHCII (1Ad) were performed by fluorescence-activated cell sorting (FACS analyses).After pancreatitis induction, pancreatic enzymes (amylase: SOP 7008 U/L, NAP 37,044 U/L, P0.001) and histologic pancreatic damage (SOP 0.80 ± 1.92, NAP 19.6 ± 0.64, P0.001) developed instantly. Pulmonary vascular damage and MPO were detected between 6 and 12 h after onset (6 h albumin SOP 132.0 ± 12.0 μg/mL, NAP 267.2 ± 49.6 μg/mL; P0.05; MPO SOP 0.23 ± 0.20 ng/mL, NAP 11.29 ± 3.12 ng/mL, P0.01). Blood levels of interleukin 6 increased after 12-24 h (12 h SOP 584 ± 300 pg/mL; NAP 2169 ± 942 pg/mL, P0.05), whereas monocytes increased fourfold within 48 h (P0.05). Furthermore, pancreatitis increased the percentage of activated monocytes in the blood (6 h and/or 48 h: MHCII (1Ad) 2196%/5.65%; CD121b 51,654%/82,146%). Similar observations were made for monocytes from the liver and spleen.Although inflammatory mediators increased during 24 h after pancreatitis induction, monocyte activation lasted for at least 48 h. The latter is not limited to blood but also detected in isolated liver and spleen monocytes.

Objectives Current guidelines tell us that intervention in severe necrotizing pancreatitis ought to be performed as late as possible. However, when pancreatic necrosis becomes infected, the necrotic tissue needs to be removed. Unfortunately, bacterial infection can only be proven by invasive methods. Methods Necrotizing pancreatitis with sterile or infected necrosis was induced in mice. Mice serum samples were examined by antibody-based protein array. After identifying candidate proteins that showed strong regulation, the serum concentration of these proteins was examined by sandwich ELISA. Then, human serum samples were collected from patients with mild pancreatitis, severe pancreatitis with and without pancreatic necrosis and patients with microbiologically proven infection of pancreatic necrosis. These serum samples were then analyzed by sandwich ELISA. Results In mice 6 proteins were strongly up-regulated and were further investigated by ELISAs. Of these proteins, CXCL16 and TRANCE (RANKL) concentrations were analyzed in human serum samples. CXCL16 and TRANCE were increased in patients with pancreatic necrosis and abdominal infection. Receiver operated characteristics showed that CXCL16 was superior in predicting infected pancreatic necrosis when compared to C-reactive protein and TRANCE. Conclusions Serum CXCL16 is increased in severe pancreatitis with infected pancreatic necrosis and identifies patients who benefit from surgical necrosectomy.

To examine bowel wall edema development in laparoscopic and open major visceral surgery. In a prospective study, 47 consecutively operated patients with gastric and pancreatic resections were included. Twenty-seven patients were operated in a conventional open procedure (open group) and 20 in a laparoscopic fashion (lap group). In all procedures, a small jejunal segment was resected during standard preparation, of which we measured the dry-wet ratio. Furthermore, HE staining was performed for measuring of bowel wall thickness and edema assessment. Mean value (±std) of dry-wet ratio was significantly lower in the open than in the lap group (0.169 ± 0.017 versus 0.179 ± 0.015; p = 0.03) with the same amount of fluid administration in both groups and a longer infusion interval during laparoscopic surgery. Subgroup analyses (only pancreatic resections) still showed similar results. Histologic examination depicted a significantly larger bowel wall thickness in the open group. Laparoscopic surgery does not seem to lead to the bowel wall edema observed to occur in open surgery regardless of the degree of intravenous fluid administration, thus supporting its use even in major visceral surgery.

The aim of the article is to investigate a new anastomotic technique compared with standardized intestinal anastomotic procedures.A total of 32 male Wistar rats were randomized to three groups. In the Experimental Group (n = 10), the new double 90 degrees inversely rotated anastomosis was used, in the End Group (n = 10) a single-layer end-to-end anastomosis, and in the Side Group (n = 12) a single-layer side-to-side anastomosis. All anastomoses were done using interrupted sutures. On postoperative day 4, rats were relaparotomized. Bursting pressure, hydroxyproline concentration, a semiquantitative adhesion score and two histological anastomotic healing scores (mucosal healing according to Chiu and overall anastomotic healing according to Verhofstad) were collected. Most data are presented as median (range). p0.05 was considered significant.Anastomotic insufficiency occurred only in one rat of the Side Group. Median bursting pressure in the Experimental Group was 105 mm Hg (range = 72-161 mm Hg), significantly higher in the End Group (164 mm Hg; range = 99-210 mm Hg; p = 0.021) and lower in the Side Group by trend (81 mm Hg; range = 59-122 mm Hg; p = 0.093). Hydroxyproline concentration did not differ significantly in between the groups. The adhesion score was 2.5 (range = 1-3) in the Experimental Group, 2 (range = 1-2) in the End Group, but there were significantly more adhesions in the Side Group (range = 3-4); p = 0.020 versus Experimental Group, p0.001 versus End Group. The Chiu Score showed the worst mucosal healing in the Experimental Group. The overall Verhofstad Score was significantly worse (mean = 2.032; standard deviation [SD] = 0.842) p = 0.031 and p = 0.002 in the Experimental Group, compared with the Side Group (mean = 1.729; SD = 0.682) and the End Group (mean = 1.571; SD = 0.612).The new anastomotic technique is feasible and did not show any relevant complication. Even though it was superior to the side-to-side anastomosis by trend with respect to functional stability, mucosal healing surprisingly showed the worst results. Classical end-to-end anastomosis still seems to be the best choice regarding structural and functional anastomotic stability.

Supplemental Digital Content is available in the text, Pancreatic ductal adenocarcinoma (PDAC) is characterized by a strong fibrotic stromal reaction and diffuse growth pattern. Peritumoral fibrosis is often evident during surgery but only distinguishable from tumor by microscopic examination. The aim of this study was to investigate the role of clearance of fibrotic stromal reaction at the mesopancreatic resection margin as a criterion for radical resection and preoperative assessment of resectability. Mesopancreatic stromal clearance status (S-status) was defined as the presence or absence (S+/S0) of fibrotic stromal reaction at the mesopancreatic resection margin. Detailed retrospective clinicopathologic re-evaluation of margin status and preoperative cross-sectional imaging was performed in a cohort of 91 patients operated for pancreatic head PDAC from 2001 to 2011. Conventional margin positive resection (R+, tumor cells directly at the margin) was found in 36%. However, S-status further divided the margin negative (R0) group into patients with median survival of 14 months versus 31 months (S+ versus S0, P = 0.005). Overall rate of S+ was 53%. S-status and lymph node ratio constituted the only independent predictors of survival. Stranding of the superior mesenteric artery fat sheath was the only independent radiologic predictor of S+ resection, and achieved a 71% correct prediction of S-status. Mesopancreatic stromal clearance is a major determinant of curative resection in PDAC, and preoperative prediction by cross-sectional imaging is possible, setting the basis for a new definition of borderline resectability.

Despite extensive efforts, pancreatic cancer remains incurable. Most risk factors, such as genetic disposition, metabolic diseases or chronic pancreatitis cannot be influenced. By contrast, cigarette smoking, an important risk factor for pancreatic cancer, can be controlled. Despite the epidemiological evidence of the detrimental effects of cigarette smoking with regard to pancreatic cancer development and its unique property of being influenceable, our understanding of cigarette smoke-induced pancreatic carcinogenesis is limited. Current data on cigarette smoke-induced pancreatic carcinogenesis indicate multifactorial events that are triggered by nicotine, which is the major pharmacologically active constituent of tobacco smoke. In addition to nicotine, a vast number of carcinogens have the potential to reach the pancreatic gland, where they are metabolized, in some instances to even more toxic compounds. These metabolic events are not restricted to pancreatic ductal cells. Several studies show that acinar cells are also greatly affected. Furthermore, pancreatic cancer progenitor cells do not only derive from the ductal epithelial lineage, but also from acinar cells. This sheds new light on cigarette smoke-induced acinar cell damage. On this background, our objective is to outline a multifactorial model of tobacco smoke-induced pancreatic carcinogenesis.

To date, there are no artificial sphincter prostheses for urinary or fecal incontinence that may be implemented elsewhere instead, for example, in the upper gastrointestinal tract. Conventional systems are conceptually similar but are constructed specifically for distinct applications and are manual in operation. The German Artificial Sphincter System (GASS) II is the evolution of a highly integrative, modular, telemetric sphincter prosthesis with more than one application. Redesigning and integrating multilayer actuators into the pump allows us to reduce the input voltage to -10 to +20 V (V(PP) = 30 V). This provides for a flow rate of 2.23 mL/min and a counterpressure stability of 260 mbar. Furthermore, multiple applications have become feasible due to our standardized connection system, therapy-specific compression units, and application-specific software. These innovations allow us to integrate not only severe fecal and urinary incontinence, erectile dysfunction, and therapy-resistant reflux disease, but also morbid adiposity into the gamut of therapeutic GASS applications.

s / Pancreatology 14 (2014) S1eS129 S101 profiles measured. EAP severity was assessed by standard biochemical parameters and blinded histopathology. Results: GSK-7975A inhibited calcium influx and necrotic pathway activation inmurine (at 3, 10 or 30 mM, p

We thank Dr Kapoor for his response to our article, in which he concisely summarizes recent data on bikunin’s effect on tumorigenesis, tumor invasion, and metastasis. Even though our main interest lies in the role that bikunin and the inter-a-trypsin inhibitor (ITI) family members have in acute systemic inflammation, it is important to point out that many molecules tie acute systemic inflammation and tumor invasion together, and ITI appears to have a profound impact on both phenomena as well as bikunin. The ITI heavy chains (ITIH) are found in the blood and are covalently bound to bikunin. They have an important role in modulating the extracellular matrix. Bikunin transfers ITIHs to hyaluronan, thus changing the structure and physiology of the hyaluronan strand. This is observed and thoroughly analyzed in acute inflammation, especially rheumatoid arthritis. Furthermore, several of the heavy chains have been associated with malignancies. Inter-a-trypsin inhibitor heavy chain 4 and its derivatives, for example, are differentially regulated in patients with prostate cancer, compared with patients with benign prostate hyperplasia [1]. Furthermore, ITIH4 is elevated in patients with breast cancer [2,3] and endometrial cancer [4]. Inter-a-trypsin inhibitor heavy chain 3 is up-regulated in patients with gastric cancer and has most recently been proposed as a biomarker for pancreatic cancer as well [5,6]. The role of ITIHs in tumorigenesis and invasion is unclear, but interaction with the extracellular matrix appears likely. Whether this function is in concert with bikunin or independent of it needs to be further examined, especially because bikunin has been shown to inhibit proteinases and thereby inhibits the metastasis of tumor cells [7]. This could account for more aggressive tumor behavior when bikunin is low. In contrast to this observation, bikunin also attenuates inflammation by exhibiting antiproteolytic activity, and consequently may even facilitate immunologic tumor escape mechanisms in some cases [8].

Objective: The accumulation of inflammatory leukocytes is a prerequisite of adipose tissue inflammation during cardiometabolic disease. We previously reported that a genetic deficiency of the intracellular signaling adaptor TRAF5 (TNF [tumor necrosis factor] receptor–associated factor 5) accelerates atherosclerosis in mice by increasing inflammatory cell recruitment. Here, we tested the hypothesis that an impairment of TRAF5 signaling modulates adipose tissue inflammation and its metabolic complications in a model of diet-induced obesity in mice. Approach and Results: To induce diet-induced obesity and adipose tissue inflammation, wild-type or Traf5 −/− mice consumed a high-fat diet for 18 weeks. Traf5 −/− mice showed an increased weight gain, impaired insulin tolerance, and increased fasting blood glucose. Weight of livers and peripheral fat pads was increased in Traf5 −/− mice, whereas lean tissue weight and growth were not affected. Flow cytometry of the stromal vascular fraction of visceral adipose tissue from Traf5 −/− mice revealed an increase in cytotoxic T cells, CD11c + macrophages, and increased gene expression of proinflammatory cytokines and chemokines. At the level of cell types, expression of TNFα, MIP (macrophage inflammatory protein)-1α, MCP (monocyte chemoattractant protein)-1, and RANTES (regulated on activation, normal T-cell expressed and secreted) was significantly upregulated in Traf5 -deficient adipocytes but not in Traf5 -deficient leukocytes from visceral adipose tissue. Finally, Traf5 expression was lower in adipocytes from obese patients and mice and recovered in adipose tissue of obese patients one year after bariatric surgery. Conclusions: We show that a genetic deficiency of TRAF5 in mice aggravates diet-induced obesity and its metabolic derangements by a proinflammatory response in adipocytes. Our data indicate that TRAF5 may promote anti-inflammatory and obesity-preventing signaling events in adipose tissue.