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.

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.

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.

[CT-colonography: current status and future directions in consideration of the technical evolution]. / Technische Neuerungen in der CT-Kolonographie: gegenwärtiger Stand und zukünftige Entwicklung.

Computertomography and with it CT-colonography evolves technically and also possibilities of data processing proceed rapidly. The current status of CTC can be summarized as follows:The method represents a true alternative to barium enema if technical conditions are given.CTC can be performed with excellent results immediately following an incomplete colonoscopy. In pretherapeutic diagnosis of colorectal carcinoma, CTC can be combined with a staging CT of the abdomen. The recent technical advances with new 16 row technology in image quality and data acquisition - mainly concerning the spatial and temporal resolution - are very promising. Developments in postprocessing of CT data can also contribute to a higher efficiency of labor. Alternative preparation schemata can lead to a more comfortable bowel cleansing and stool labeling can even avoid this procedure, resulting both in an even improved compliance. Radiation exposure in low dose technique is comparable to a double contrast barium enema and can be still reduced by optimisation of scanning parameters.The aim of the following article is (1 to give an overview of the current status of patient preparation, image acquisition and data processing; (2) to review recent clinical trials and experimental studies and to show future directions of CTC with regard to the clinical development.

[Anastomotic insufficiencies of the esophagus--early surgical endoscopy and endoscopic therapy]. / Anastomoseninsuffizienzen am Osophagus--Frühoperative Endoskopie und endoskopische Therapie.

Therapeutic value of flexible endoscopy regarding treatment of esophagoenteric anastomotic leakage was retrospectively analyzed in 56 patients (female n = 13, male n = 43, age 60 years, 1/1992-4/2000). Endoscopic treatment was performed in 44 patients (self-expanding metal stent n = 38, fibrin glue n = 16, feeding tube/decompression tube n = 20, endoscopic percutaneous jejunostomy n = 8), interventional radiological technique in 4 patients and surgical treatment in 11 patients. All patients with open surgical reintervention developed reinsufficiency of the anastomosis. Successful endoscopic therapy was achieved in 75% with a mortality of 21.4%. Endoscopic treatment of esophageal anastomotic insufficiency is an effective alternative to conventional re-thoracotomy. The appropriate endoscopic intervention needs to be decided individually depending on diagnosis and location.

[Diagnosis of suture dehiscence in the gastrointestinal tract. "Sufficiency" of radiology and endoscopy]. / Diagnostik der Nahtinsuffizienz im Gastrointestinaltrakt. "Suffizienz" von Radiologie und Endoskopie.

Since radiological methods are standard for the diagnosis of anastomotic insufficiencies in the gastrointestinal tract, endoscopy, with direct access to the crucial site for visual verification and direct application of contrast media, offers remarkable advantages in diagnostic efficiency. Additional, immediate therapeutic management of these threatening conditions, especially in critical and problematic cases, is possible by interventional endoscopy.

[Enteral feeding of problem patients: replacement of surgical catheter jejunostomy by an endoscopic concept]. / Enterale Ernährung bei Problempatienten: Ersatz der operativen Katheterjejunostomie durch endoskopisches Konzept.

Percutaneous endoscopic gastrostomy (PEG), is widely used as a safe, effective method of providing enteral nutrition to patients in whom oral feeding is not possible. However, in patients with malnutrition after partial or total gastrectomy, anastomotic insufficiency after gastric resection or esophageal resection with gastric pull-up, esophageal perforation and fistulas, the stomach cannot be punctured. In these cases endoscopic percutaneous jejunostomy (EPJ) by direct punction of the small intestine is a reasonable alternative; the technique is described, and the results of a series of 103 EPJs are reported.

Actions of lipoproteins in cultured human mesangial cells: modulation by mitogenic vasoconstrictors.

Recent studies have suggested that hypercholesterolemia may aggravate glomerulosclerosis. Mesangial cells actively participate in this process. To elucidate mechanisms by which lipids act on human mesangial cells (HMC), we measured the receptor-specific uptake of apolipoprotein (Apo) B- and Apo B- and E-containing lipoproteins in the presence and absence of growth factors and studied the growth-related mechanisms in HMC after exposure to low-density lipoprotein (LDL). Human LDL and very low density beta-lipoprotein (beta-VLDL) isolated from cholesterol-fed rabbits were bound, internalized, and degraded by a receptor-specific mechanism (dissociation constants for degradation LDL 30.0 and for beta-VLDL 4.1 micrograms protein/ml medium). Maximal capacities were 30-50% of those of human fibroblasts. Acetylated and copper-oxidized LDL were not taken up specifically, suggesting no active scavenger-receptor activity. Preexposure to endothelin-1 (5 x 10(-7) M) and platelet-derived growth factor (PDGF A, B, 83 x 10(-12) M) for 16 or 15 h, respectively, doubled the uptake of LDL by HMC. In addition, PDGF synergized with LDL in stimulating DNA synthesis. Exposure of HMC to LDL resulted in a transient elevation of mRNA that encodes c-fos and c-jun, with a maximal effect seen after 30-60 min. In addition, PDGF A- and B-chain mRNAs were transiently elevated, peaking at 3 h in response to LDL (25 micrograms protein/ml medium) and continued to increase in a concentration-dependent manner (25-75 micrograms protein/ml medium). These data demonstrate that HMC take up lipoproteins via a receptor-specific mechanism with a high affinity for Apo E-containing lipoproteins which are often found in plasma of patients with renal disease. Vasoconstrictor and mitogenic peptides enhance lipoprotein receptor activity and have a synergistic effect on the mitogenic effect of LDL. LDL stimulates a number of growth-related genes. These data suggest that lipoproteins may play a critical role in mediating mesangial cell hypertrophy or proliferation, events intimately involved in the development of glomerulosclerosis.