Implementation of Current ENETS Guidelines for Surgery of Small (≤2 cm) Pancreatic Neuroendocrine Neoplasms in the German Surgical Community: An Analysis of the Prospective DGAV StuDoQ|Pancreas Registry.

BACKGROUND: 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. METHODS: Data from the prospective StuDoQ|Pancreas registry of the German Society of General and Visceral Surgery were analyzed regarding patient's demographics, tumor characteristics, surgical procedures, histology and perioperative outcomes. RESULTS: Eighty-four (29.2%) of 287 patients had sporadic pNENs ≤2 cm. Forty-three (51.2%) patients were male, and the mean age at diagnosis was 58.8 ± 15.6 years. Twenty-five (29.8%) pNENs were located in the pancreatic head. The diagnosis pNEN was preoperatively established in 53 (65%) of 84 patients. Sixty-two (73.8%) patients had formal pancreatic resections, including partial pancreaticoduodenectomy or total pancreatectomy (21.4%). Only 22 (26.2%) patients underwent parenchyma-sparing resections and 23 (27.4%) patients had minimally invasive procedures. A lymphadenectomy was performed in 63 (75.4%) patients, and lymph node metastases were diagnosed in 6 (7.2%) patients. Eighty-two (97.7%) patients had an R0 resection. Sixty (72%) tumors were classified G1, 24 (28%) tumors G2. Twenty-seven (32.2%) of 84 patients had postoperative relevant Clavien-Dindo grade ≥3 complications. Thirty- and 90-day mortalities were 2.4% and 3.6%. CONCLUSIONS: ENETS guidelines for surgery of small pNENs are yet not well accepted in the German surgical community, since the rate of formal resections with standard lymphadenectomy is high and the minimally invasive approach is underused. The attitude to operate small NF tumors seems to be rather aggressive.

Indications for resection and perioperative outcomes of surgery for pancreatic neuroendocrine neoplasms in Germany: an analysis of the prospective DGAV StuDoQ|Pancreas registry.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

[Day Surgery for Endoscopic Inguinal Hernia Repair]. / Minimalinvasive Leistenhernienchirurgie ­ TEP ambulant.

BACKGROUND: Whereas international guidelines recommend day surgery for endoscopic inguinal hernia repair, this approach is still controversial in Germany. In the light of international guidelines and at the request of patients, we have established total extraperitoneal patch plastic (TEP) surgery in the outpatient setting in our hospital. METHODS: A retrospective analysis of all unilateral TEP procedures carried out between January 2013 and December 2015 in our outpatient surgery, focused on postoperative complications, conversion to admission and rate of recurrence. Patient satisfaction with the outpatient setting was evaluated by telephone interview. RESULTS: In the 3 year period analysed, 164 patients were admitted for day surgery. Outpatient surgery was carried out in 152 patients, whereas 12 patients had to be admitted overnight due to circulatory disturbance, pain or bleeding. A total of 102 patients could be questioned for follow-up. Hematoma developed in 9 patients, and recurrence of hernia in 3 patients. Infections or seromas were not described or detected. 88 patients were very satisfied with the outpatient procedure, and 82 patients would clearly prefer day surgery again. CONCLUSIONS: Unilateral endoscopic hernia repair is safe and can be performed in the outpatient setting without increased risk. Satisfaction and acceptance by the patients is high. There is a dramatic difference between day surgery and inpatient procedure in the costs for hernia repair and this is one of the major reasons why outpatient endoscopic hernia repair is still rare in Germany.

Pre-emptive endoscopic vacuum therapy for treatment of anastomotic ischemia after esophageal resections.

Background and study aims Endoscopic vacuum therapy (EVT) is a promising new approach for the treatment of anastomotic leakage in the gastrointestinal tract. Here, we present the first case series demonstrating successful use of EVT for the treatment of post-esophagectomy anastomotic ischemia prior to development of leakage. Patients and methods Between 2012 and 2015, intraluminal EVT was performed in eight patients with anastomotic ischemia following esophagectomy. The primary outcome measure was successful mucosal recovery. Secondary outcome measures were duration of treatment, number of sponge changes, septic course, and associated complications. Results Complete mucosal recovery was achieved in six patients (75 %) with different degrees of anastomotic ischemia. In two patients (25 %), small anastomotic leaks developed, which resolved by continuing the EVT treatment. Median duration of EVT treatment until mucosal recovery was 16 days (range 6 - 35), with a median of 5 sponge changes per patient (range 2 - 11). No EVT-associated complications were noted. Three patients developed anastomotic stenoses, which were treated by endoscopic dilation therapy. Conclusion This is the first case series to demonstrate that the early use of EVT potentially modulates clinical outcomes and infection parameters in patients with anastomotic ischemia following esophagectomy. Further studies are needed to define the indications and patients who are most likely to benefit from early EVT.

Downregulation of CX3CR1 ameliorates experimental colitis: evidence for CX3CL1-CX3CR1-mediated immune cell recruitment.

PURPOSE: Inflammatory conditions like inflammatory bowel diseases (IBD) are characterized by increased immune cell infiltration. The chemokine ligand CX3CL1 and its receptor CX3CR1 have been shown to be involved in leukocyte adhesion, transendothelial recruitment, and chemotaxis. Therefore, the objective of this study was to describe CX3CL1-CX3CR1-mediated signaling in the induction of immune cell recruitment during experimental murine colitis. METHODS: Acute colitis was induced by dextran sodium sulfate (DSS), and sepsis was induced by injection of lipopolysaccharide (LPS). Serum concentrations of CX3CR1 and CX3CL1 were measured by ELISA. Wild-type and CX3CR1-/- mice were challenged with DSS, and on day 6, intravital microscopy was performed to monitor colonic leukocyte and platelet recruitment. Intestinal inflammation was assessed by disease activity, histopathology, and neutrophil infiltration. RESULTS: CX3CR1 was upregulated in DSS colitis and LPS-induced sepsis. CX3CR1-/- mice were protected from disease severity and intestinal injury in DSS colitis, and CX3CR1 deficiency resulted in reduced rolling of leukocytes and platelets. CONCLUSIONS: In the present study, we provide evidence for a crucial role of CX3CL1-CX3CR1 in experimental colitis, in particular for intestinal leukocyte recruitment during murine colitis. Our findings suggest that CX3CR1 blockade represents a potential therapeutic strategy for treatment of IBD.

Successful closure of defects in the upper gastrointestinal tract by endoscopic vacuum therapy (EVT): a prospective cohort study.

BACKGROUND: Perforations and anastomotic leakages of the upper gastrointestinal (GI) tract cause a high morbidity and mortality rate. Only limited data exist for endoscopic vacuum therapy (EVT) in the upper GI tract. METHODS: Fifty-two patients (37 men and 15 women, ages 41-94 years) were treated (12/2011-12/2015) with EVT for anastomotic insufficiency secondary to esophagectomy or gastrectomy (n = 39), iatrogenic esophageal perforation (n = 9) and Boerhaave syndrome (n = 4). After diagnosis, polyurethane sponges were endoscopically positioned with a total of 390 interventions and continuous negative pressure of 125 mm of mercury (mmHg) was applied to the EVT-system. Sponges were changed endoscopically twice per week. Clinical and therapy-related data and mortality were analyzed. RESULTS: After 1-25 changes of the sponge at intervals of 3-5 days with a mean of 6 sponge changes and a mean duration of therapy of 22 days, the defects were healed in 94.2 % of all patients without revision surgery. In three patients (6 %), EVT failed. Two of these patients died due to hemorrhage related to EVT. Four postinterventional strictures were observed during the follow-up of up to 4 years. CONCLUSION: Esophageal wall defects of different etiology in the upper gastrointestinal tract can be treated successfully with EVT, considering that indication for EVT should be weighed carefully. EVT can be regarded as a novel life-saving therapeutic tool.

A two-step multidisciplinary approach to treat recurrent esophageal strictures in children with epidermolysis bullosa dystrophica.

In children with severe generalized recessive dystrophic epidermolysis bullosa (RDEB), esophageal scarring leads to esophageal strictures with dysphagia, followed by malnutrition and delayed development. We describe a two-step multidisciplinary therapeutic approach to overcome malnutrition and growth retardation. In Step 1, under general anesthesia, orthograde balloon dilation of the esophagus is followed by gastrostomy creation using a direct puncture technique. In Step 2, further esophageal strictures are treated by retrograde dilation via the established gastrostomy; this step requires only a short sedation period. A total of 12 patients (median age 7.8 years, range 6 weeks to 17 years) underwent successful orthograde balloon dilation of esophageal strictures combined with direct puncture gastrostomy. After 12 and 24 months in 11 children, a substantial improvement of growth and nutrition was achieved (body mass index [BMI] standard deviation score [SDS] + 0.59 and + 0.61, respectively). In one child, gastrostomy was removed because of skin ulcerations after 10 days. Recurrent esophageal strictures were treated successfully in five children. The combined approach of balloon dilation and gastrostomy is technically safe in children with RDEB, and helps to promote catch-up growth and body weight. In addition, recurrent esophageal strictures can be treated successfully without general anesthesia in a retrograde manner via the established gastrostomy.

The microRNA-200 family--a potential diagnostic marker in hepatocellular carcinoma?

BACKGROUND: Hepatocellular carcinoma (HCC) represents the main cause of death among patients with cirrhotic liver disease, but little is known about mechanisms of cirrhosis associated carcinogenesis. We investigated the diagnostic impact of microRNA-200 (miR-200) family members as important epigenetic regulators of epithelial-mesenchymal transition (EMT) to differentiate between patients with HCC and liver cirrhosis. METHODS: Expression of the miR-200 family was investigated by qRT-PCR in specimens of HCC patients with and without cirrhosis. Benign specimens with and without cirrhosis served as controls. Expression of the EMT markers ZEB-1, E-cadherin and vimentin was examined using immunohistochemistry. RESULTS: MiR-200a and miR-200b were significantly downregulated in HCC (miR-200a: -40.1% (P = 0.0002); miR-200b: -52.3% (P = 0.0002)), and in HCC cirrhotic tissue (miR-200a: -40.2% (P = 0.004); miR-200b: -51.1% (P = 0.007)) compared to liver cirrhosis. Spearman's Rho analysis revealed a significant negative correlation of miR-200a and miR-200b to the expression of the mesenchymal markers Vimentin (P < 0.007) and ZEB-1 (P < 0.0005) and a significant positive correlation to the epithelial marker E-cadherin (P < 0.0002). CONCLUSIONS: MiR-200 family members and their targets are significantly deregulated in HCC and liver cirrhosis. The miR-200 family is able to distinguish between cirrhotic and HCC tissue and could serve as an early marker for cirrhosis-associated HCC.

Tissue factor: a mediator of inflammatory cell recruitment, tissue injury, and thrombus formation in experimental colitis.

There is growing evidence for an interplay between inflammatory and coagulation pathways in acute and chronic inflammatory diseases. However, it remains unclear whether components of the coagulation pathway, such as tissue factor (TF), contribute to intestinal inflammation, and whether targeting TF will blunt the inflammatory cell recruitment, tissue injury, and enhanced thrombus formation that occur in experimental colitis. Mice were fed 3% dextran sodium sulfate (DSS) to induce colonic inflammation, with some mice receiving a mouse TF-blocking antibody (muTF-Ab). The adhesion of leukocytes and platelets in colonic venules, light/dye-induced thrombus formation in cremaster muscle microvessels, as well as disease activity index, thrombin-antithrombin (TAT) complexes in plasma, and histopathologic changes in the colonic mucosa were monitored in untreated and muTF-Ab-treated colitic mice. In untreated mice, DSS elicited the recruitment of adherent leukocytes and platelets in colonic venules, caused gross and histologic injury, increased plasma TAT complexes, and enhanced thrombus formation in muscle arterioles. muTF-Ab prevented elevation in TAT complexes, reduced blood cell recruitment and tissue injury, and blunted thrombus formation in DSS colitic mice. These findings implicate TF in intestinal inflammation and support an interaction between inflammation and coagulation in experimental colitis.

Blended learning in surgery using the Inmedea Simulator.

BACKGROUND: Recently, medical education in surgery has experienced several modifications. We have implemented a blended learning module in our teaching curriculum to evaluate its effectiveness, applicability, and acceptance in surgical education. METHODS: In this prospective study, the traditional face-to-face learning of our teaching curriculum for fourth-year medical students (n = 116) was augmented by the Inmedea Simulator, a web-based E-learning system, with six virtual patient cases. Student results were documented by the system and learning success was determined by comparing patient cases with comparable diseases (second and sixth case). The acceptance among the students was evaluated with a questionnaire. RESULTS: After using the Inmedea Simulator, correct diagnoses were found significantly (P < 0.05) more often, while an incomplete diagnostic was seen significantly (P < 0.05) less often. Significant overall improvement (P < 0.05) was seen in sixth case (62.3 ± 5.6 %) vs. second case (53.9 ± 5.6 %). The questionnaire revealed that our students enjoyed the surgical seminar (score 2.1 ± 1.5) and preferred blended learning (score 2.5 ± 1.2) to conventional teaching. CONCLUSION: The blended learning approach using the Inmedea Simulator was highly appreciated by our medical students and resulted in a significant learning success. Blended learning appears to be a suitable tool to complement traditional teaching in surgery.

Regional anesthetic procedures in immunosuppressed patients: risk of infection.

PURPOSE OF REVIEW: Due to demographic developments anesthesiologists encounter an increasing number of older and multimorbid patients in their daily routine. Consequently the proportion of immunosuppressed patients (e.g. those with cancer, diabetes mellitus, and those receiving immunosuppressive treatment and/or chemotherapy - e.g. for inflammatory bowel diseases, autoimmune diseases, and after transplantation) will also rise. Regional anesthesia (peripheral nerve blocks and neuraxial blockade) may be beneficial in these patients and will have to be considered in order to provide adequate pain management and minimize risks for the patients. RECENT FINDINGS: There is only little available research and data on regional anesthesia procedures in specific immunosuppressed patient population. However, recent analyses from great databases dealing with general postoperative pain management have been published. SUMMARY: So far, there are no guidelines available dealing with indications and limitations of regional anesthetic procedures in these patients. The complication rate is rare but potentially disastrous. However, the technique itself cannot be regarded as absolute contraindication for immunosuppressed patients if precautions are taken. An interdisciplinary approach regarding the indication of regional anesthesia techniques in immunosuppressed patients is recommended. Efforts must therefore be made to achieve an interdisciplinary consensus with relevant risk-benefit considerations.

On the dynamics of nitrite, nitrate and other biomarkers of nitric oxide production in inflammatory bowel disease.

Nitrite and nitrate are frequently used surrogate markers of nitric oxide (NO) production. Using rat models of acute and chronic DSS-induced colitis we examined the applicability of these and other NO-related metabolites, in tissues and blood, for the characterization of inflammatory bowel disease. Global NO dynamics were assessed by simultaneous quantification of nitrite, nitrate, nitroso and nitrosyl species over time in multiple compartments. NO metabolite levels were compared to a composite disease activity index (DAI) and contrasted with measurements of platelet aggregability, ascorbate redox status and the effects of 5-aminosalicylic acid (5-ASA). Nitroso products in the colon and in other organs responded in a manner consistent with the DAI. In contrast, nitrite and nitrate, in both intra- and extravascular compartments, exhibited variations that were not always in step with the DAI. Extravascular nitrite, in particular, demonstrated significant temporal instabilities, ranging from systemic drops to marked increases. The latter was particularly evident after cessation of the inflammatory stimulus and accompanied by profound ascorbate oxidation. Treatment with 5-ASA effectively reversed these fluctuations and the associated oxidative and nitrosative stress. Platelet activation was enhanced in both the acute and chronic model. Our results offer a first glimpse into the systemic nature of DSS-induced inflammation and reveal a greater complexity of NO metabolism than previously envisioned, with a clear dissociation of nitrite from other markers of NO production. The remarkable effectiveness of 5-ASA to abrogate the observed pattern of nitrite instability suggests a hitherto unrecognized role of this molecule in either development or resolution of inflammation. Its possible link to tissue oxygen consumption and the hypoxia that tends to accompany the inflammatory process warrants further investigation.

Anesthesia for balloon dilatation of esophageal strictures in children with epidermolysis bullosa dystrophica: from intubation to sedation.

PURPOSE OF REVIEW: Dystrophic epidermolysis bullosa is a rare disease mainly affecting small children. They often have to undergo different surgical procedures, for example balloon dilatation following esophageal strictures to maintain oral intake and prevent malnutrition. RECENT FINDINGS: So far, no specific treatment is available for patients with any forms of epidermolysis bullosa. However, more and more minimal invasive surgical techniques are used to manage symptoms of the disease, for example endoscopic balloon dilatation for severe esophageal strictures. SUMMARY: In this article implications for the anesthetic management of children with dystrophic epidermolysis bullosa are described. General anesthesia and sedation techniques are feasible if specific prerequisites are fulfilled. The team providing anesthesia and endoscopy must be familiar with the nature and disabilities of this disease. Coordinated care of the involved disciplines is crucial for all planned procedures regarding perioperative management.

Long-Term Quality of Life Assessment After Successful Endoscopic Vacuum Therapy of Defects in the Upper Gastrointestinal Tract Quality of Life After EVT.

BACKGROUND: Accumulating 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. METHODS: We 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. RESULTS: The 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 19 months for EVT patients and 21 months 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 21 days (p < 0.001). CONCLUSION: EVT in the uGIT is well tolerated by the patients and accompanied by a satisfactory long-term QoL.

Impact of nighttime procedures on outcomes after liver transplantation.

BACKGROUND: Sleep deprivation is a well-known risk factor for the performance of medical professionals. Solid organ transplantation (especially orthotopic liver transplantation (oLT)) appears to be vulnerable since it combines technically challenging operative procedures with an often unpredictable start time, frequently during the night. Aim of this study was to analyze whether night time oLT has an impact on one-year graft and patient survival. MATERIAL AND METHODS: Deceased donor oLTs between 2006 and 2017 were retrospectively analyzed and stratified for recipients with a start time at day (8 a.m. and 6 p.m.) or at night (6 p.m. to 8 a.m.). We examined donor as well as recipient demographics and primary outcome measure was one-year patient and graft survival. RESULTS: 350 oLTs were conducted in the study period, 154 (44%) during daytime and 196 (56%) during nighttime. Donor and recipient variables were comparable. One-year patient survival (daytime 75.3% vs nighttime 76.5%, p = 0.85) as well as graft survival (daytime 69.5% vs nighttime 73.5%, p = 0.46) were similar between the two groups. Frequencies of reoperation (daytime 53.2% vs nighttime 55.1%, p = 0.74) were also not significantly different. CONCLUSION: Our retrospective single center data derived from a German transplant center within the Eurotransplant region provides evidence that oLT is a safe procedure irrespective of the starting time. Our data demonstrate that compared to daytime surgery nighttime liver transplantation is not associated with a greater risk of surgical complications. In addition, one-year graft and patient survival do not display inferior results in patients undergoing nighttime transplantation.

The weekend effect in liver transplantation.

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.

Apolipoprotein A-IV inhibits experimental colitis.

The antiatherogenic properties of apoA-IV suggest that this protein may act as an anti-inflammatory agent. We examined this possibility in a mouse model of acute colitis. Mice consumed 3% dextran sulfate sodium (DSS) in their drinking water for 7 days, with or without daily intraperitoneal injections of recombinant human apoA-IV. apoA-IV significantly and specifically delayed the onset, and reduced the severity and extent of, DSS-induced inflammation, as assessed by clinical disease activity score, macroscopic appearance and histology of the colon, and tissue myeloperoxidase activity. Intravital fluorescence microscopy of colonic microvasculature revealed that apoA-IV significantly inhibited DSS-induced leukocyte and platelet adhesive interactions. Furthermore, apoA-IV dramatically reduced the upregulation of P-selectin on colonic endothelium during DSS-colitis. apoA-IV knockout mice exhibited a significantly greater inflammatory response to DSS than did their WT littermates; this greater susceptibility to DSS-induced inflammation was reversed upon exogenous administration of apoA-IV to knockout mice. These results provide the first direct support for the hypothesis that apoA-IV is an endogenous anti-inflammatory protein. This anti-inflammatory effect likely involves the inhibition of P-selectin-mediated leukocyte and platelet adhesive interactions.