After Intestinal Transplantation Kidney Function Is Impaired by Downregulation of Epithelial Ion Transporters in the Ileum.

BACKGROUND: Intestinal transplantation is a treatment option for intestinal failure. Although nephrotoxic medication after transplantation is a major cause for posttransplant renal insufficiency, it remains unclear why kidney dysfunction is particularly frequent after intestinal transplantation. METHODS: This study analyzed messenger RNA expression of NHE3, DRA, and CFTR in 404 biopsies obtained between day 2 and 1508 from the terminal ileum of 10 adult intestinal transplant recipients. RESULTS: The time courses of immunosuppression and glomerular filtration rate were correlated. In the first posttransplant year, expression of NHE3 and DRA, which mediate NaCl absorption, was diminished to a greater degree than that of CFTR, which mediates chloride secretion. Reduced NHE3 and DRA expression was associated with high tacrolimus trough levels. Titration of tacrolimus to low levels by year 2 was paralleled by partially restored NHE3 and DRA expression. In cell culture experiments, similar effects of tacrolimus on transporter expression were detected. In patients, both reduced tacrolimus levels and recovery of NHE3 and DRA expression were associated with stabilization of renal function. CONCLUSIONS: Our data strongly suggest that tacrolimus impairs absorption of NaCl and water from the transplanted ileum, leading to volume depletion and impaired renal function. This may be reversible by reduction of tacrolimus to lower levels without increased rates of rejection or chronic graft failure.

[OTSC-assisted resection of a duodenal neuroendocrine tumor: a case report]. / OTSC-assistierte Resektion eines neuroendokrinen Tumors im Duodenum: Ein Fallbericht.

The over the scope clip (OTSC) is mainly used for closure of gastrointestinal endoluminal defects and treatment of gastrointestinal bleeding. Its use for resection of subepithelial tumors or full-thickness resection is still under investigation. Duodenal neuroendocrine tumors (NET) are rare neoplasms. Endoscopic resection is appropriate up to a size of 20  mm, however positive deep margins are a frequent challenge in these subepithelial tumors. We report on a 60-year-old male patient who had undergone endoscopic mucosal resection with R1 deep margins of a NET (G1) in the duodenal bulb. To avoid local surgical resection in this multimorbid patient, we performed OTSC-assisted deep resection. Complete resection (R0) was achieved, and no complications occurred. Our report suggests that OTSC-assisted resection of subepithelial tumors is a possible and safe option, especially for patient's and in locations with a high perioperative risk.

Transpapillary retrieval of a proximally migrated stent using a three-prong polyp retrieval device in a 2-years-old girl.

Endoscopic retrieval of proximally migrated biliary stents is sometimes challenging. We report on the successful use of a three-prong colon polyp retrieval device in a two year old child.

[Current MRI staging of rectal cancer]. / Aktuelle MRT-Diagnostik des Rektumkarzinoms.

Colorectal carcinoma is the second most prevalent cause for cancer, and has very variable outcomes. Advancements in surgery, the change from adjuvant to neo-adjuvant radio-chemo-therapies as well as in clinical diagnostics have improved the prognosis for patients in a multi-modal therapy concept. An accurate primary staging including a reliable prediction of the circumferential resection margin (CRM) has established MR Imaging (MRI) beside intraluminal endoscopic ultrasound (EUS). MRI facilitates the selection of patients likely to benefit from a preoperative therapy, especially in cases of unfavorable factors. Currently the relationship of the tumor to the mesorectal fascia has become a more important prognostic factor than the T-staging, particularly for surgical therapy. In addition further prognostic factors like the depth of infiltration into the perirectal fat and the extramural venous infiltration (EMVI) have important impact on therapy and prognosis. High resolution MRI has proved useful in clarifying the relationship between the tumor and the mesorectal fascia, which represents the CRM at the total mesorectal excision (TME) especially in the upper and middle third. Preoperative evaluation of the other prognostic factors as well as the nodal status is still difficult. It is used increasingly not only for primary staging but also progressively for the monitoring of neoadjuvant therapy. The addition of diffusion weighted imaging (DWI) is an interesting option for the improvement of response evaluation. The following overview provides an introduction of MRI diagnosis as well as its importance for the evaluation of the clinically relevant prognostic factors leading to an improvement of therapy and prognosis of patients with rectal carcinoma.

Gene expression analysis in chronic postradiation proctopathy.

PURPOSE: Radiotherapy is one of the important treatment modalities for tumors of pelvic organs. The fixed location of the rectum and its anatomic relationship with other pelvic organs makes it prone to radiation injury resulting in chronic radiation proctopathy in 5% to 20% of patients. Endothelial dysfunction has been associated with a number of pathophysiological processes. Endothelial cells synthesize and release various factors that regulate angiogenesis, inflammatory responses, hemostasis, as well as vascular tone and permeability. METHODS: Rectum tissue samples from 20 patients with established chronic radiation proctopathy were analysed for the expression of genes related to oxidative stress, tissue hypoxia, angiogenesis, and inflammation [endoglin (ENG), activin receptor-like kinase 1 (ALK1), platelet endothelial cell adhesion molecule 1 (PECAM), vascular endothelial growth factor (VEGF), fibroblast growth factor 2 (FGF2), hypoxia-inducible factor 1 (HIF-1), and interleukin-1 beta (IL-1ß)]. RESULTS: Overexpression of HIF-1, VEGF, FGF2, and IL-1ß was detected in affected tissue. For the first time, a significant suppression of activin receptor-like kinase 1 and ENG could be revealed. CONCLUSION: The data provided here allow further insight into the pathogenesis of radiation-induced rectum injury. Radiation-induced damage is not confined to a single event but involves complex signaling between different pathways, enhancing and maintaining the processes that lead to mucosal damage. The results indicate that postradiation tissue hypoxia is critical for fibrosis, which involves changes in the expression of profibrotic and angiogenic factors in rectal tissue.

Effort, safety, and findings of routine preoperative endoscopic evaluation of morbidly obese patients undergoing bariatric surgery.

BACKGROUND: Obesity is becoming an epidemic health problem and is associated with concomitant diseases, such as sleep apnea syndrome and gastroesophageal reflux disease (GERD). There is no standardized diagnostic workup for the upper gastrointestinal tract in obese patients; many patients have no upper gastrointestinal symptoms, and few data are available on safety of endoscopy in morbidly obese patients. METHODS: Sixty-nine consecutive diagnostic upper gastrointestinal endoscopies in morbidly obese patients (26 men, 43 women; mean age 43.4 +/- 10.9 years) were prospectively evaluated from January to December 2008 in an outpatient setting before bariatric procedures. Sedation was administered with propofol. Data on sedation, critical events, and examination times were recorded, as well as pathological findings. RESULTS: The patients' mean body mass index was 47.6 +/- 7.9 (range, 35.1-73.3) kg/m(2); 17.4% reported GERD symptoms. The mean duration of the endoscopy procedure (including sedation) was 20.3 +/- 9.3 (range, 5-50) min, and the whole procedure (including preparation and postprocessing) took 58.2 +/- 19 (range, 20-120) min. The mean propofol dosage was 380 +/- 150 (range, 80-900) mg. Two patients had critical events that required bronchoscopic intratracheal O(2) insufflation due to severe hypoxemia (<60% SaO: (2)). Nearly 80% of patients had pathological findings in the upper gastrointestinal tract. Only 20% reported upper gastrointestinal symptoms. Pathologic conditions were found in the esophagus in 23.2% of the patients, in the stomach in 78.2%, and in the duodenum in 11.6%. The prevalence of Helicobacter pylori infection was 8.7%. CONCLUSIONS: Upper gastrointestinal endoscopy can be performed safely. However, careful monitoring and anesthesiological support are required for patients with concomitant diseases and those receiving sedation. Because 80% of the patients with pathological findings were asymptomatic, every morbidly obese patient should undergo endoscopy before bariatric surgery because there may be findings that might change the surgical strategy.

Laparoscopic-assisted transgastric cholecystectomy and secure endoscopic closure of the transgastric defect in a survival porcine model.

BACKGROUND AND STUDY AIMS: Natural orifice transluminal endoscopic surgery holds promise for surgical interventions. Before the feasibility of this technique can be established, however, secure sealing of the transluminal access needs to be thoroughly investigated. PATIENTS AND METHODS: Following antibiotic prophylaxis and gastric disinfection, nine pigs underwent transgastric cholecystectomy by means of a flexible endoscope with the aid of a transabdominal 5-mm trocar. The gastric wall was punctured and dilated. The gallbladder was retracted with a laparoscopic grasper. The cystic duct and artery were dissected with a flexible monopolar ball electrode. The cystic duct was interrupted with flexible scissors between endoclips. Cholecystectomy was completed and the gallbladder was retrieved through the stomach. The gastric defect was closed using a single modified over-the-scope clip (OTSC) (Ovesco, Tübingen, Germany) and grasping the serosal and muscle layer of the gastric wall. The animals were sacrificed 4 weeks later. RESULTS: Laparoscopic-assisted transgastric cholecystectomy was successful in all cases without significant perioperative complications. All animals survived without postoperative complications. The mean operating time was 128 minutes (range, 85 - 205 minutes). The gastric defect closure resulted in inversion of the gastric wall layers within an average time of 6.8 +/- 5 minutes. At 4 weeks postoperative, only minimal thin adhesions were observed in the right hypochondrium. CONCLUSIONS: We found gastric closure using the OTSC to be a reliable tool for closing the transgastric access. Laparoscopic-assisted transgastric cholecystectomy by means of a flexible endoscope was technically feasible, but remains a demanding procedure.

Dysfunction of the lower esophageal sphincter and dysmotility of the tubular esophagus in morbidly obese patients.

BACKGROUND: Morbid obesity is associated with gastroesophageal reflux (GERD). The aim of this prospective study was to determine esophageal motility in asymptomatic morbidly obese patients and compare it to non-obese individuals. METHODS: Forty-seven morbidly obese patients without GERD symptoms and 15 normal weight individuals were divided into four groups according to their body mass index (BMI; group I, <30 kg/m2; group II, 35-39.9 kg/m2; group III, 40-49.9 kg/m2; group IV, >or=50 kg/m2). Standard stationary water-perfused manometry was performed for the assessment of anatomy and function of the lower esophageal sphincter (LES). Twenty-four-hour ambulatory pH-metry and measurement of esophageal motility were performed with a microtransducer sleeve catheter. Data are given as mean+/-SD, and the results of groups II-IV were compared to the non-obese individuals from group I. RESULTS: Patients with morbid obesity had significantly lower LES pressures than non-obese individuals (I, 15.1+/-4.9; II-IV, 10.5+/-5.4, mmHg, p<0.05 vs. I) and showed an altered esophageal motility with respect to contraction frequency (I, 1.8+/-0.7/min; II-IV, 3.6+/-2.5/min; p<0.05 vs. I) and contraction amplitude (I, 38+/-12 mmHg; II-IV, 33+/-17 mmHg; p<0.05 vs. I). Furthermore, these patients had significantly higher DeMeester scores than non-obese individuals. Length and relaxation of the LES as well as propulsion velocity of the tubular esophagus did not differ. CONCLUSION: Patients with morbid obesity (=BMI>40 kg/m2) have a dysfunction of the LES and an altered esophageal motility, even when they are asymptomatic for GERD symptoms.

Endoscopic treatment of gastric perforation caused by acute necrotizing pancreatitis using over-the-scope clips: a case report.

Gastric perforation is a rare complication after acute necrotizing pancreatitis. We describe endoscopic closure of a gastric perforation that appeared 4 days after surgical necrosectomy including splenectomy due to necrotizing pancreatitis, using the over-the-scope clip (OTSC) system (Ovesco Endoscopy GmbH, Tübingen, Germany). The clips, which are made of nitinol, are loaded onto an application cap which is mounted on the distal tip of the endoscope. The lesion was closed with two clips and the patient recovered well without reinterventions. The lesions showed normal healing on follow-up.

The postoperative course of gamma-glutamyl transpeptidase--a marker of cytomegalovirus (CMV) replication risk?

Cytomegalovirus (CMV) infection is a common complication in the postoperative course of liver transplantation. In order to start early prophylactic therapy, but to avoid unnecessary treatment, or expensive screening, a desirable goal in post-transplant monitoring is to find appropriate markers in standard laboratory diagnostics. In the present study, the results of a 6-week CMV replication monitoring schedule by the pp65 antigenemia assay in 100 liver graft recipients were included. The activities of transaminases, glutamate dehydrogenase and gamma-glutamyl transpeptidase (gamma-GT) were measured by routine laboratory methods. In contrast to the transaminases, the serum activity of gamma-GT increased during the first postoperative week. The maximum levels were 246 +/- 211 U/l in patients without (n = 46) and 140 +/- 89 U/l in patients with early CMV replication (n = 54; p = 0.02). Patients with gamma-GT levels below 200 U/l on the 5th postoperative day (n = 72) had a CMV replication risk of 65%, whereas those patients with gamma-GT levels above this threshold had a risk of 30% (n = 28; p = 0.0007; relative risk = 2.9). These findings provide a routinely usable marker for the identification of patients at an increased risk of CMV replication. It can be considered that these phenomena may be caused by an additional immunosuppressive effect of the CMV virus.

Diagnosis and management of pheochromocytomas in patients with multiple endocrine neoplasia type 2-relevance of specific mutations in the RET proto-oncogene.

It has been suggested that specific mutations in the RET proto-oncogene correlate with clinical manifestation of the multiple endocrine neoplasia type 2 (MEN 2) syndrome. We retrospectively analyzed 61 patients with MEN 2, 28 with associated pheochromocytoma, regarding the relevance of specific mutations in the RET proto-oncogene and the diagnostic sensitivity of catecholamine screening and localization procedures. The present study shows that the position of the RET mutation is related to disease phenotype; codon 634 mutations are predictive of families predisposed to pheochromocytoma. In 18% of our patients, the diagnosis of pheochromocytoma preceded detection of medullary thyroid carcinoma. Therefore, mutation analysis of the RET gene should be performed in apparently "sporadic" cases of pheochromocytoma to confirm or exclude MEN 2. The most sensitive biochemical marker for pheochromocytoma in MEN 2 is 24-h urinary epinephrine excretion. Computed tomography, magnetic resonance imaging and MIBG scintigraphy are all highly sensitive methods to localize pheochromocytoma. We conclude that, in all families with MEN 2, mutational analysis of the RET proto-oncogene should be performed, both to identify gene carriers for MEN 2 and to identify specific mutations that are more strongly associated with pheochromocytoma.