Philipp Busch

Resection vs drainage in treatment of chronic pancreatitis: long-term results of a randomized trial.

BACKGROUND & AIMS Tailored organ-sparing procedures have been shown to alleviate pain and are potentially superior in terms of preservation of endocrine and exocrine function as compared with standard resection (Whipple) for chronic pancreatitis with inflammatory pancreatic head tumor. Long-term results comparing these 2 procedures have not been published so far. The aim of this study was to report on long-term results of a randomized trial comparing a classical resective procedure (pylorus-preserving Whipple) with an extended drainage procedure (Frey) for chronic pancreatitis. METHODS All patients who participated in a previously published randomized trial on the perioperative course comparing both procedures were contacted with a standardized, validated, quality of life and pain questionnaire. Additionally, patients were seen in the outpatient clinic to assess endocrine and exocrine pancreatic function by an oral glucose tolerance test and fecal chymotrypsin test. RESULTS There were no differences between both groups regarding quality of life, pain control, or other somatic parameters after a median of 7 years postoperatively. Correlations among continuous alcohol consumption, endocrine or exocrine pancreatic function, and pain were not found. CONCLUSIONS Both procedures provide adequate pain relief and quality of life after long-term follow-up with no differences regarding exocrine and endocrine function. However, short-term results favor the organ-sparing procedure.

Genetic variation may influence obesity only under conditions of diet: Analysis of three candidate genes

Under the hypothesis of obesity as a polygenetic disease numerous genes have been associated with an obese phenotype and metabolic co-morbidities. The cannabinoid receptor 1 (CB 1) is part of an underinvestigated system that participates in appetite control. Previous publications suggest that the endocannabinoid systems interact with the better understood leptin-melanocortin axis. Neuropeptide Y (NPY) is a player in the latter. Finally resistin has been shown to influence NPY expression in the brain. In a cohort of 1721 caucasion men and women with a BMI of 25kg/m(2) or more we therefore investigated three candidate polymorphisms at baseline and following 3 months low fat caloric restriction diet by polymerase chain reaction and restriction digestion: the 1359 G/A variant of the cannabinoid receptor 1 (CB1), the L7P variation in neuropeptide Y (NPY) and the -420C>G polymorphism in resistin. Comparing groups according to genotype for each gene separately revealed significant results at baseline only for the CB1 gene. However, upon dieting significant data was found for all 3 genes. Carriers of at least one A allele in CB1 lost more weight and reduced LDL cholesterol more than wildtype patients. LL homocygotes in NPY had a greater reduction in glucose, triglycerides, and LDL cholesterol whereas in resistin carriers of the G allele had a greater reduction in weight and triglycerides. Creating two groups defined by NPY and resistin genotype, respectively, with similar BMI values resulted in significant differences concerning weight loss and metabolic improvement. In conclusion, genetic polymorphisms associated with obesity may become relevant only under the condition of a low calory diet. The presence of a certain genotype may then be beneficial for obesity treatment.

A pathogenic role for T cell–derived IL-22BP in inflammatory bowel disease

Interleukin-22 binding protein (IL-22BP) drives inflammatory bowel disease by sopping up the tissue-protective protein IL-22. Intestinal inflammation can impair mucosal healing, thereby establishing a vicious cycle leading to chronic inflammatory bowel disease (IBD). However, the signaling networks driving chronic inflammation remain unclear. Here we report that CD4+ T cells isolated from patients with IBD produce high levels of interleukin-22 binding protein (IL-22BP), the endogenous inhibitor of the tissue-protective cytokine IL-22. Using mouse models, we demonstrate that IBD development requires T cell–derived IL-22BP. Lastly, intestinal CD4+ T cells isolated from IBD patients responsive to treatment with antibodies against tumor necrosis factor–α (anti–TNF-α), the most effective known IBD therapy, exhibited reduced amounts of IL-22BP expression but still expressed IL-22. Our findings suggest that anti–TNF-α therapy may act at least in part by suppressing IL-22BP and point toward a more specific potential therapy for IBD.

Decreased frequency of CD73+CD8+ T cells of HIV-infected patients correlates with immune activation and T cell exhaustion

Recent studies indicate that murine Tregs highly express the ENTDP1, as well as the 5′‐NT and thereby, suppress Teff function by extracellular adenosine production. Furthermore, CD73 seems to play a role as costimulatory molecule for T cell differentiation. In this study, we analyzed the expression of CD73 on peripheral and lymph nodal Teffs and Tregs in a cohort of 95 HIV patients at different stages of disease, including LTNP and ECs. In contrast to murine Tregs, CD73 was only expressed on a small minority (∼10%) of peripheral Tregs. In contrast, we see high expression of CD73 on peripheral CD8+ T cells. In HIV infection, CD73 is markedly reduced on all Teffs and Tregs, regardless of the memory subtype. On CD8+ T cells, a positive correlation between CD73 expression and CD4 counts (P=0.0003) was detected. CD73 expression on CD8+ T cells negatively correlated with HLA‐DR (<0.0001) and PD1 (P=0.0457) expression. The lower CD73 expression on CD8+ T cells was partially reversible after initiation of ART (P=0.0016). Functionally, we observed that CD8+CD73+ T cells produce more IL‐2 upon HIV‐specific and unspecific stimulation than their CD73− counterparts and show a higher proliferative capacity. These data indicate that down‐regulation of CD73 on CD8+ T cells correlates with immune activation and leads to functional deficits in HIV infection.

Autoimmune Renal Disease Is Exacerbated by S1P-Receptor-1-Dependent Intestinal Th17 Cell Migration to the Kidney

Summary Th17 cells are most abundant in the gut, where their presence depends on the intestinal microbiota. Here, we examined whether intestinal Th17 cells contribute to extra-intestinal Th17 responses in autoimmune kidney disease. We found high frequencies of Th17 cells in the kidneys of patients with antineutrophil cytoplasmatic antibody (ANCA)-associated glomerulonephritis. We utilized photoconversion of intestinal cells in Kaede mice to track intestinal T cell mobilization upon glomerulonephritis induction, and we found that Th17 cells egress from the gut in a S1P-receptor-1-dependent fashion and subsequently migrate to the kidney via the CCL20/CCR6 axis. Depletion of intestinal Th17 cells in germ-free and antibiotic-treated mice ameliorated renal disease, whereas expansion of these cells upon Citrobacter rodentium infection exacerbated pathology. Thus, in some autoimmune settings, intestinal Th17 cells migrate into target organs, where they contribute to pathology. Targeting the intestinal Th17 cell “reservoir” may present a therapeutic strategy for these autoimmune disorders.

Heme oxygenase-1 germ line GTn promoter polymorphism is an independent prognosticator of tumor recurrence and survival in pancreatic cancer

Heme oxygenase‐1 (HO‐1) correlates with aggressive tumor behavior and chemotherapy resistance in pancreatic cancer (PC). We evaluated the prognostic value of the basal transcription controlling germ line GTn repeat polymorphism (GTn) in the promoter region of the HO‐1 gene in PC.

Upper Gastrointestinal Endoscopy prior to Bariatric Surgery-Mandatory or Expendable? An Analysis of 801 Cases

BackgroundUpper gastrointestinal pathologies are common in bariatric patients. Preoperative esophagogastroduodenal endoscopy (EGD) should detect and treat pathologies that might alter the type of bariatric surgery. However, clinical consequences of these findings are often insignificant. The aim of this study was to assess the influence of preoperative endoscopy in our cohort and its clinical consequences.MethodsWe conducted a retrospective analysis of endoscopic findings in patients under evaluation for bariatric surgery. Endoscopic findings were compared to preoperative risk factors as well as postoperative complications, and its clinical consequences were analyzed.ResultsData was available for 801 patients. Abnormal endoscopic findings were found in 65.7% of all patients. The most common conditions were gastritis (32.1%) and gastroesophageal reflux (24.8%). Malignancies were observed in 0.5% of all patients. We observed early-stage adenocarcinoma of the esophagus in two patients through our routine preoperative evaluation. Helicobacter pylori infections were detected in preoperative biopsies in only 3.7% of all patients. Patients who reported reflux symptoms had a higher rate of pathological EGDs (74.2 vs. 64.9%, p .019). We did not find any other risk factors for a pathological endoscopy. The postoperative complication rate was 11.2%. Leakage rate was 1.1%. Mortality rate was 0.4%. We did not find any correlation between the incidence of postoperative complications and preoperative endoscopic findings.ConclusionsRelevant findings in routine preoperative endoscopy are rare but have significant influence on decision-making in bariatric patients and should be assessed as a necessary diagnostic tool.

Mentorship Programs in Bariatric Surgery Reduce Perioperative Complication Rate at Equal Short-Term Outcome—Results from the OPTIMIZE Trial

ObjectivesThe aim of this study was to determine the efficacy of coaching on outcome in low volume centers of excellence and to evaluate the influence of mentorship programs on the center development.BackgroundThe number of bariatric procedures has increased steadily in the last years. Providing nationwide bariatric care on a high professional level needs structures to train and guide upcoming centers and ensure high quality in patient care.MethodsA prospective multicentered, observational study including laparoscopic sleeve gastrectomies (SG) and Roux-en-Y gastric bypass (RYGB) procedures was performed. Twelve emerging bariatric centers were coached by five experienced bariatric centers. Surgeons of the mentor centers gave guidance on pre- and postsurgical management of their patients including complications and proctored the first interventions. The results were compared regarding operative outcomes, percentage of excess weight loss, complications, and resolution of comorbidities.ResultsA total of 214 of 293 patients (73.0%) completed the study. The most frequently reported complications were wound infection (4.4%), disorder of emptying stomach/new reflux (2.4%), anastomotic leaks, intra-abdominal secondary hemorrhage, and dumping syndrome (2.0% each). The mortality rate was zero. We found no difference in overall complication rates or resolution of obesity-related comorbidities when comparing experienced surgeons with less experienced surgeons.ConclusionsOur results suggest that under the conditions of the practices of this study, coaching and mentoring were associated with comparable outcomes both in experienced and emerging centers. In addition, mentorship programs ensure equal outcome quality in terms of improvement of obesity-associated comorbidities.Trial RegistrationNCT Number: NCT01754194.