Malignant gastroduodenal obstruction: retrospective comparison of endoscopic and surgical palliative therapy.

INTRODUCTION: Endoscopic stenting (ES) is a minimally invasive alternative to surgical gastroenterostomy (GE) for palliation of malignant gastroduodenal obstructions. This consecutive, retrospective analysis compares the clinical outcome of all patients undergoing ES or GE in the same period. METHODS: ES was performed at the Endoscopy Department, University Hospital Mannheim or at the Interdisciplinary Endoscopy Department, University Hospital Hamburg-Eppendorf. GE was performed at the Surgical Department, University Hospital Mannheim. All palliative ES or GE on patients with malignant gastroduodenal obstruction without earlier gastric resections between January 2001 and April 2007 were evaluated. Main outcome measurements were ability of solid food intake (gastric outlet obstruction score), persistence of nausea and vomiting (gut function score), length of hospital stay, morbidity, mortality and re-interventions. RESULTS: A total of 44 ES and 43 GE were performed. Nausea and vomiting--measured by means of the gut function score--persisted in significantly more patients in the GE group than in those who underwent stent placement (p = 0.0102). The gastric outlet obstruction score at discharge from the hospital revealed no significant difference in the ability of solid food intake between the groups. The hospital stay was significantly longer in the GE group (p = 0.0003). There was no significant difference in mortality and the rates of complications and re-interventions. CONCLUSION: In this study, ES is a generally equivalent--and in several points superior--alternative to GE for palliation of malignant gastroduodenal obstruction. ES seems to be the less invasive alternative for symptomatic patients. GE has good results in patients with longer survival and can be practiced within abdominal explorations.

Endoscopic full-thickness resection and defect closure in the colon.

BACKGROUND: Endoscopic full-thickness resection (eFTR) is a minimally invasive method for en bloc resection of GI lesions. OBJECTIVE: The aim of this pilot study was to evaluate the feasibility of a grasp-and-snare technique for eFTR combined with an over-the-scope clip (OTSC) for defect closure. DESIGN: Nonsurvival animal study. SETTING: Animal laboratory. ANIMALS: Fourteen female domestic pigs. INTERVENTIONS: The eFTR was performed in porcine colons using a novel tissue anchor in combination with a standard monofilament snare and 14 mm OTSC. In the first group (n = 20), closure of the colonic defects with OTSC was attempted after the resection. In the second group (n = 8), an endoloop was used to secure the resection base before eFTR was performed. RESULTS: In the first group (n = 20), eFTR specimens ranged from 2.4 to 5.5 cm in diameter. Successful closure was achieved in 9 out of 20 cases. Mean burst pressure for OTSC closure was 29.2 mm Hg (range, 2-90; SD, 29.92). Injury to adjacent organs occurred in 3 cases. Lumen obstruction due to the OTSC closure occurred in 3 cases. In the second group (n = 8), the diameter of specimens ranged from 1.2 to 2.2 cm. Complete closure was achieved in all cases, with a mean burst pressure of 76.6 mm Hg (range, 35-120; SD, 31). Lumen obstruction due to the endoloop closure occurred in one case. No other complications or injuries were observed in the second group. LIMITATIONS: Nonsurvival setting. CONCLUSIONS: Colonic eFTR using the grasp-and-snare technique is feasible in an animal model. Ligation of the resection base with an endoloop before eFTR seems to reduce complication rates and improve closure success and leak test results despite yielding smaller specimens.

Endoscopic closure of duodenal perforations by using an over-the-scope clip: a randomized, controlled porcine study.

BACKGROUND: Duodenal perforations during diagnostic upper endoscopy are rare; however, when therapeutic techniques are performed, the reported incidence is as great as 2.8%. Surgical repair is usually mandated, but it is associated with significant morbidity and mortality. OBJECTIVE: To compare closure of duodenal perforations by using an over-the-scope clip (OTSC) with a surgical closure. DESIGN: Randomized, controlled animal study. SETTING: Animal facility laboratory. ANIMALS: Domestic pigs (24 females). INTERVENTIONS: Large (10-mm) duodenal perforations were created by using an endoscopic needle-knife. The animals were randomly assigned to either open surgical repair (n=12) or endoscopic closure by using the OTSC system (n=12). Pressurized leak tests were performed during necropsy. MAIN OUTCOME MEASUREMENTS: One major bleed occurred because of a liver injury during creation of the duodenotomy. Mean time for endoscopic closure was 5 minutes (range, 3-8 min; SD +/- 2). No complications occurred during any of the closure procedures. At necropsy, all OTSC and surgical closures demonstrated complete sealing of duodenotomy sites. Pressurized leak tests demonstrated a mean burst pressure of 166 mm Hg (range, 80-260; SD +/- 65) for OTSC closures and 143 mm Hg (range, 30-300, SD +/- 83) for surgical sutures. Ex vivo intact duodenal specimens exhibited a mean burst pressure of 247 mm Hg (range, 200-300; SD +/- 35), which was significantly higher compared with in vivo OTSC and surgical closures (P < .01). There were no significant differences between burst pressures of OTSC and surgical closures (P = .461). LIMITATIONS: Nonsurvival setting. CONCLUSIONS: Endoscopic closure of duodenal perforations by using the OTSC system is comparable with surgical closure in a nonsurvival porcine model. This technique is easy to perform and seems suitable for repairing duodenal perforations.

Deficiency of ATP2C1, a Golgi ion pump, induces secretory pathway defects in endoplasmic reticulum (ER)-associated degradation and sensitivity to ER stress.

Relatively few clues have been uncovered to elucidate the cell biological role(s) of mammalian ATP2C1 encoding an inwardly directed secretory pathway Ca2+/Mn2+ pump that is ubiquitously expressed. Deficiency of ATP2C1 results in a human disease (Hailey-Hailey), which primarily affects keratinocytes. ATP2C1-encoded protein is detected in the Golgi complex in a calcium-dependent manner. A small interfering RNA causes knockdown of ATP2C1 expression, resulting in defects in both post-translational processing of wild-type thyroglobulin (a secretory glycoprotein) as well as endoplasmic reticulum-associated protein degradation of mutant thyroglobulin, whereas degradation of a nonglycosylated misfolded secretory protein substrate appears unaffected. Knockdown of ATP2C1 is not associated with elevated steady state levels of ER chaperone proteins, nor does it block cellular activation of either the PERK, ATF6, or Ire1/XBP1 portions of the ER stress response. However, deficiency of ATP2C1 renders cells hypersensitive to ER stress. These data point to the important contributions of the Golgi-localized ATP2C1 protein in homeostatic maintenance throughout the secretory pathway.