Marco Bueter

Bariatric surgery, also known as metabolic surgery, is an effective treatment for morbid obesity which also offers pronounced metabolic effects including the resolution of type 2 diabetes and a decrease in cardiovascular disease and long-term cancer risk. However, the mechanisms of surgical weight loss and the long term consequences of bariatric surgery remain unclear. Bariatric surgery has been demonstrated to alter the composition of both the microbiome and the metabolic phenotype. We observed a marked shift towards Gammaproteobacteria, particularly Enterobacter hormaechei, following Roux-en-Y gastric bypass (RYGB) surgery in a rat model compared with sham operated controls. Fecal water from RYGB surgery rats was highly cytotoxic to rodent cells (mouse lymphoma cell line), although In contrast, fecal water from sham operated animals showed no/very low cytotoxicity. This shift in the gross structure of the microbiome correlated with greatly increased cytotoxicity in a regulatory acceptable mouse lymphoma assay. Urinary phenylacetylglycine and indoxyl sulfate and fecal GABA, putrescine, tyramine and uracil were found to be inversely correlated with cell survival rate. This profound co-dependent response of mammalian and microbial metabolism to RYGB surgery and the impact on the cytotoxicity of the gut luminal environment suggests that RYGB exerts local and global metabolic effects which may have an influence on long term cancer risk and cytotoxic load.

Background: The local and systemic activation and regulation of the immune system by malignant cells during carcinogenesis is highly complex with involvement of the innate and acquired immune system. Despite the fact that malignant cells do have antigenic properties their immunogenic effects are minor suggesting tumor induced mechanisms to circumvent cancer immunosurveillance. The aim of this study is the analysis of tumor immune escape mechanisms in a colorectal liver metastases mouse model at different points in time during tumor growth. Methods: CT26.WT murine colon carcinoma cells were injected intraportally in Balb/c mice after median laparotomy using a standardized injection technique. Metastatic tumor growth in the liver was examined by standard histological procedures at defined points in time during metastatic growth. Liver tissue with metastases was additionally analyzed for cytokines, T cell markers and Fas/Fas-L expression using immunohistochemistry, immunofluorescence and RT-PCR. Comparisons were performed by analysis of variance or paired and unpaired t test when appropriate. Results: Intraportal injection of colon carcinoma cells resulted in a gradual and time dependent metastatic growth. T cells of regulatory phenotype (CD4+CD25+Foxp3+) which might play a role in protumoral immune response were found to infiltrate peritumoral tissue increasingly during carcinogenesis. Expression of cytokines IL-10, TGF-β and TNF-α were increased during tumor growth whereas IFN-γ showed a decrease of the expression from day 10 on following an initial increase. Moreover, liver metastases of murine colon carcinoma show an up-regulation of FAS-L on tumor cell surface with a decreased expression of FAS from day 10 on. CD8+ T cells express FAS and show an increased rate of apoptosis at perimetastatic location. Conclusions: This study describes cellular and macromolecular changes contributing to immunological escape mechanisms during metastatic growth in a colorectal liver metastases mouse model simulating the situation in human cancer.

Der Übersichtsartikel „Operative Techniken und deren Outcome in der metabolischen Chirurgie: Sleeve-Gastrektomie“ der Kollegen Hüttl et al. beschäftigt sich mit der laparoskopischen Schlauch­magenoperation („Sleeve-Gastrektomie“) zur operativen Therapie der morbiden Adipositas (Zentralblatt für Chirurgie 2009; 134: 24–31). Nach Analyse der verfügbaren Literatur und eigener Ergebnisse kommen die Autoren zu dem Schluss, dass die laparoskopische Schlauchmagenoperation heute als ein effektiver Standardeingriff zur Therapie der Adipositas angesehen werden darf. Wir möchten ­einige Inhalte des Artikels kommentieren. The review article “Operative Techniques and Outcomes in Metabolic Surgery: ­Sleeve Gastrectomy” by Hüttl et al. is con­cerned with laparoscopic sleeve stomach operations (“sleeve gastrectomy”) for the surgical treatment of morbid obesity (Zentralblatt für Chirurgie 2009; 134: 24–31). After an analysis of the available literature and own results, the authors concluded that the laparoscopic sleeve operation is established today as an effective standard procedure in the therapy for obesity. We would like to comment on the content of this article.

The aim of this study was to evaluate whether gastric bypass with or without vagal preservation resulted in a different outcome.

Long-term complications after laparoscopic gastric banding (LAGB) are frequent, leading to reoperations for a substantial number of patients. It is not known whether esophageal motility or the lower esophageal sphincter (LES) play a role in the development of complications. The results of preoperative upper gastrointestinal (GI) testing were compared with outcome after LAGB. Before LAGB, 68 bariatric patients had esophageal manometry, endoscopy, and pH monitoring. For 61 of these patients (90% follow-up rate), the differences in weight loss, complications, and reoperation rate were retrospectively compared. Of these patients, 8.2% had a nonspecific motility disorder of the esophagus, 44.3% had an incompetent sphincter shown by manometry, and 17.5% had acid reflux shown by pH monitoring. Endoscopic evaluation showed esophagitis in 10.3% and hiatal hernia in 33.8% of the patients. Abnormal pH monitoring and endoscopic findings were not predictive for the long-term outcome or complications. The presence of an incompetent LES led to reoperation for a greater number of patients (44.4 vs. 14.7%; p = 0.01), especially if the band was placed using the pars flaccida technique. Endoscopy and pH monitoring do not predict outcome for gastric banding and therefore have no relevance in the selection of patients for gastric banding. Patients with an incompetent LES shown by manometry had a higher reoperation rate. If this finding can be confirmed, patients with LES incompetence may need another intervention.

The development of new therapeutic strategies for treatment of metastasized colorectal carcinoma requires biologically relevant and adequate animal models that generate both reproducible metastasis and the dissemination of tumor cells in the form of so-called minimal residual disease (MRD), an expression of the systemic character of neoplastic disease.

Left Ventricular Mass (LVM) is reported higher in patients (pts) with atherosclerotic renal artery stenosis (RAS) than in well matched control subjects.We plann