Andreas Thalheimer

Morbidity of Temporary Loop Ileostomy in Patients With Colorectal Cancer

PurposeThis study was designed to quantify the temporary loop ileostomy-related morbidity in patients with colorectal cancer and contrast the morbidity rates after ileostomy closure before, during, and after the start of adjuvant therapy.MethodsBetween 1997 and 2004, 120 patients with colorectal carcinoma underwent colorectal resection and creation of a temporary loop ileostomy to protect the low anastomosis. Stoma-related complications and perioperative morbidity after ileostomy closure were assessed retrospectively by reviewing the medical records.ResultsSixteen of the 120 patients (13.3 percent) suffered stoma-related complications, requiring early ileostomy closure in three. After ileostomy closure, anastomotic leakage of the ileoileostomy occurred in 3 of the 120 patients (2.5 percent), 2 of them died postoperatively (1.7 percent). The rate of minor complications (16.7 percent in all patients) was much higher in patients undergoing adjuvant chemotherapy or radiochemotherapy (25.5 percent) than in patients receiving no additional therapy (9.2 percent). In the former patients, there was a trend toward fewer complications when ileostomy closure was performed before (12.5 percent), rather than during (42.9 percent) or after (21.2 percent), the start of adjuvant therapy.ConclusionsThe morbidity following closure of a temporary loop ileostomy in colorectal cancer patients is much higher in patients receiving adjuvant chemotherapy or radiochemotherapy. The morbidity, however, might possibly be lowered to the level of patients receiving no additional therapy if ileostomy closure is performed before the start of adjuvant therapy.

Long-term benefits of Roux-en-Y pouch reconstruction after total gastrectomy: a randomized trial.

Objective:Roux-en-Y reconstruction with and without jejunal pouch was compared in a randomized controlled trial to identify the optimal reconstruction procedure in terms of quality of life. Background Data:Randomized trials comparing techniques of reconstruction after total gastrectomy have shown controversial results. Methods:One hundred and thirty-eight patients with gastric cancer were intraoperatively randomized for Roux-en-Y reconstruction with pouch (n = 71) or without pouch (n = 67) after gastrectomy and stratified into curative or palliative resection. Intra- and postoperative complications were recorded. Body weight and quality of life were determined every 6 months with a follow-up of up to 12 years. Results:Both groups were comparable for age, sex, incidence of concomitant disease, and staging. There were no differences in operative time, postoperative complications, and mortality. Short- and long-term weight loss was similar in both groups. In the first postoperative year, there were no benefits of pouch reconstruction in terms of quality of life, independent of the resection status. In the third, fourth, and fifth year after surgery quality of life was significantly improved for patients with a pouch. Conclusions:Roux-en-Y pouch reconstruction after gastrectomy is simple to perform and safe. Long-term survivors benefit from pouch reconstruction. Therefore, a pouch is recommended for patients with a good prognosis.

Expression Profiling and Genetic Alterations of the Selenoproteins GI-GPx and SePP in Colorectal Carcinogenesis

The trace element selenium is discussed as a chemopreventive agent in colorectal carcinogenesis. Selenocysteine-containing proteins, so-called selenoproteins, represent potential molecular targets for nutritive selenium supplementation. Due to their antioxidative potential, the selenoproteins gastrointestinal glutathione peroxidase (GI-GPx) and selenoprotein P (SePP) are considered to provide protection against reactive oxygen species (ROS), thereby reducing DNA damage and preventing development of colon cancer. GI-GPx and SePP are abundantly expressed in normal colon mucosa. Recently, we demonstrated both reduced SePP expression and increased GI-GPx expression in colorectal adenomas. In this study, we investigated the expression of SePP and GI-GPx in colorectal cancers compared with corresponding normal mucosa. Further, the occurrence of genetic alterations within the SePP and GI-GPx genes was analyzed. We observed a significant reduction or loss of SePP mRNA expression in colon cancers, whereas GI-GPx mRNA and protein expression varied between different tumor samples. In addition, we identified novel polymorphisms within the SePP and GI-GPx genes with so far unknown relevance for protein function. Our results argue against a general decrease of selenoprotein expression in colorectal carcinogenesis but imply specific differential regulation of expression of individual selenoproteins.

Band Erosion and Passage, Causing Small Bowel Obstruction

A rare complication of adjustable gastric banding is reported. A 65-year-old man developed recurrent vomiting, epigastric pain, and small-bowel obstruction 13 months after laparoscopic adjustable gastric banding for morbid obesity. Investigation revealed that the band had migrated completely into the gastric lumen and had passed far down the jejunum. The band was still connected by the tubing to the port chamber. By laparoscopy, the band was cut at the stomach, and removed via a jejunotomy. Postoperative course was uneventful. Complete band migration requires early removal of the band.

A complex DNA-repeat structure within the Selenoprotein P promoter contains a functionally relevant polymorphism and is genetically unstable under conditions of mismatch repair deficiency

Epidemiological data, animal studies and interventional studies provide evidence for a potential chemopreventive effect of selenium during development of colorectal cancer. The human glycoprotein Selenoprotein P (SeP) contains up to 50% of plasma selenium content. SeP is expressed in the gastrointestinal tract and the liver, where its expression is downregulated by various proinflammatory cytokines (Il1β, TGFβ, IFNγ). Previously, we have demonstrated dramatically reduced SeP expression in human colon adenomas. Here, we have identified a complex (A)4-C-(A)4-GG-(A)8-GCT-(TC)5-(T)17 (bp −429 to bp − 477) repeat structure within the SeP promoter and we have analysed this regulatory DNA sequence with respect to polymorphisms, genomic instability and functional relevance to promoter activity. As opposed to the (TC)5 variant we identified a novel (TC)3 polymorphism within this repeat in the general population, which conferred significantly reduced basal promoter activity to reporter gene constructs in HepG2 cells. Allelic distribution of this (TC)n element was similar in colon carcinoma patients and healthy controls. Additionally, we observed genetic instability within the (T)17 repeat motif in colon cancers of the mutator phenotype. This instability of the (T)17 repeat had no effect on basal promoter activity in reporter gene assays. In conclusion, we characterised a complex repeat structure within the SeP promoter that may be of functional relevance to SeP gene expression. Further studies on the effect of different SeP promoter genotypes on SeP protein expression and disease susceptibility are needed.

Paternity testing after pregnancy termination using laser microdissection of chorionic villi.

Abstract We report an unusual case of paternity testing from residues of chorionic villi 5 weeks after pregnancy termination. The autopsy of a 32-year-old female homicide victim revealed the presence of intact chorionic villi at the former placenta implantation site. Fetal cells were selectively isolated by laser-induced microdissection of the remaining villi to avoid contamination with maternal DNA. Simultaneous amplification of 12 STR loci in 2 PCR reactions resulted in a combined probability of paternity of 99.94%. This case demonstrates that laser-assisted microdissection and multiplex STR typing provide tools for paternity testing performed on endometrial mucosa long after the product of conception was removed by therapeutic abortion.

Evaluation of immunological escape mechanisms in a mouse model of colorectal liver metastases

BackgroundThe 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.MethodsCT26.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.ResultsIntraportal 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.ConclusionsThis 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.

The concurrence of histologically positive resection margins and sessile morphology is an important risk factor for lymph node metastasis after complete endoscopic removal of malignant colorectal polyps

IntroductionThe optimal procedure to be followed after colonoscopic polypectomy of malignant colorectal polyps with nontumour-free resection margins at histology is a matter of controversy. While some authors recommend merely local or segmental follow-up resection, others favour an oncological resection.Patients and methodsOne hundred five patients, each with a single malignant polyp, were investigated. Patients with a macroscopically evident malignant polyp and those in whom the endoscopist reported incomplete polypectomy were excluded from the study.ResultsPostpolypectomy morbidity was 4%, and postoperative was 14%. In only 39 cases were the resection margins adjudged to be tumour-free. Histology following subsequent surgery or the follow-up examinations revealed a local recurrence or residual carcinoma at the polypectomy site in only three (2.8%) cases and lymph node metastasis in eight (7.6%) cases. Five patients had remnant adenoma at the polypectomy site. Of the high-risk factors, histological incomplete removal (n = 66, p = 0.04, odds ratio (OR) 10.2) and lymph vessel infiltration (n = 7, p = 0.02, OR 9.2) revealed a significant correlation with lymph node metastasis, but not with remnant tumour. In the case of sessile polyp, the assessment of histological incomplete removal was highly significantly correlated with lymph node metastasis (n = 55, p = 0.007, OR 18.1).ConclusionsPolypectomy artefacts appear to be responsible for the discrepancy between histology and the tumour remnants actually present. On the other hand, histologically incompletely removed sessile malignant polyps represent an appreciably higher risk for lymph node metastasis. Such cases should, therefore, be submitted to further oncological resection.

Bariatric surgery for morbid obesity in craniopharyngioma

To retrospectively analyse the effectiveness of bariatric surgery for hypothalamic obesity in patients with craniopharyngioma (CP).

Duodenal-jejunal bypass improves glycemia and decreases SGLT1-mediated glucose absorption in rats with streptozotocin-induced type 2 diabetes.

Objective:To elucidate whether duodenal-jejunal-bypass (DJB), which improves blood glucose control, changes activity of Na+-D-glucose cotransporter SGLT1 in small intestine. Background:DJB has been shown to improve oral glucose tolerance in normal rats and a genetic diabetic rat model. Because intestinal D-glucose absorption is mediated by SGLT1 localized in the brush border membrane of small intestinal enterocytes, it is unclear whether function of SGLT1 is altered by DJB and whether this contributes to the improvement of glycemic control. Methods:A high-fat diet and low-dose streptozotocin administration were used to induce a type 2 diabetes in male Lewis rats. The diabetic animals underwent DJB or sham surgery. An oral glucose tolerance test (OGTT) was used to evaluate glucose control 3 weeks after surgery. SGLT1-mediated glucose transport was assessed using everted rings of different small intestinal segments. SGLT1 mRNA expression was determined by quantitative reverse transcription polymerase chain reaction (RT-PCR). Results:DJB improved the OGTT significantly (P < 0.001) compared with sham-operated rats while body weight was not different among the surgical groups. DJB induced a 50% reduction of SGLT1-mediated glucose uptake into enterocytes of duodenum and jejunum (P < 0.001). The concentration of D-glucose in the blood following glucose gavage increased more slowly after DJB versus sham. Conclusions:The data indicate that DJB surgery decreases glucose absorption in the small intestine by downregulation of SGLT1-mediated glucose uptake. We suggest that the downregulation of SGLT1 contributes to the body-weight independent improvement of diabetes type 2.