Over-the-Scope Clips Are More Effective Than Standard Endoscopic Therapy for Patients With Recurrent Bleeding of Peptic Ulcers.

BACKGROUND & AIMS: Endoscopic hemostasis is effective in treatment of bleeding peptic ulcers. However, rebleeding is difficult to treat and associated with substantial morbidity and mortality. We performed a prospective randomized trial to determine whether over-the-scope clips (OTSCs) are more effective than standard treatment of severe recurrent upper gastrointestinal bleeding. METHODS: We performed our study at 9 academic referral centers (in Germany, Switzerland, and Hong Kong) from March 2013 through September 2016. Adult patients with recurrent peptic ulcer bleeding following initially successful hemostasis (66 patients in the intent-to-treat analysis) were randomly assigned to groups (1:1) that underwent hemostasis with either OTSC or standard therapy. Standard therapy was defined as hemostasis with through-the-scope clips (TTSC, n = 31) or thermal therapy plus injection with diluted adrenaline (n = 2). The primary endpoint was further bleeding (a composite endpoint of a persistent bleeding despite endoscopic therapy according to the protocol or recurrent bleeding within 7 days after successful hemostasis). Patients with further bleeding were allowed to cross over to OTSC therapy. Main secondary endpoints were mortality, necessity of surgical or angiographic salvage therapy, duration of stay in the hospital or intensive care, number of blood units transfused, and complications associated with endoscopic therapy. RESULTS: Persistent bleeding after per-protocol hemostasis was observed in 14 patients (42.4%) in the standard therapy group and 2 patients (6.0%) in the OTSC group (P = .001). Recurrent bleeding within 7 days occurred in 5 patients (16.1%) in the standard therapy group vs 3 patients (9.1%) in the OTSC group (P = .468). Further bleeding occurred in 19 patients (57.6%) in the standard therapy group and in 5 patients (15.2%) in the OTSC group (absolute difference 42.4%; 95% confidence interval 21.6-63.2; P = .001) Within 30 days of follow-up, 1 patient in the standard therapy group (3.0%) and 1 patient in the OTSC group (3.0%) required surgical therapy (P = .999). Within 30 days of the procedure, 2 patients died in the standard therapy group (6.3%) and 4 patients died in the OTSC group (12.1%) (P = .672). There were no significant differences in the other secondary endpoints. CONCLUSIONS: In prospective randomized trial, we found endoscopic treatment with OTSCs to be superior to standard therapy with TTSCs for patients with recurrent peptic ulcer bleeding. STING Study, Clinicaltrials.gov no: NCT1836900.

Rendezvous endoscopic recanalization for complete esophageal obstruction.

BACKGROUND AND STUDY AIM: Complete esophageal obstruction after (chemo)radiation for head and neck cancers is rare. However, inability to swallow one's own saliva strongly inflicts upon quality of life. Techniques for endoscopic recanalization in complete obstruction are not well established. We assessed the efficacy and safety of rendezvous recanalization. PATIENTS AND METHODS: We performed a retrospective review of all patients who underwent endoscopic recanalization of complete proximal esophageal obstruction after radiotherapy between January 2009 and June 2016. Technical success was defined as an ability to pass an endoscope across the recanalized lumen, clinical success by changes in the dysphagia score. Adverse events were recorded prospectively. RESULTS: 19 patients with complete obstruction (dysphagia IV°), all of whom had failed at least one trial of conventional dilatation, underwent recanalization by endoscopic rendezvous, a combined approach through a gastrostomy and perorally under fluoroscopic control. Conscious sedation was used in all patients. In 18/19 patients (94.7%), recanalization was technically successful. In 14/18 patients (77.8%), the post-intervention dysphagia score changed to ≤ II. Three patients had their PEG removed. Factors negatively associated with success were obstruction length of 50 mm; and tumor recurrence for long-term success. No severe complications were recorded. CONCLUSIONS: Rendezvous recanalization for complete esophageal obstruction is a reliable and safe method to re-establish luminal patency. Differences between technical and clinical success rates highlight the importance of additional functional factors associated with dysphagia. Given the lack of therapeutic alternatives, rendezvous recanalization is a valid option to improve dysphagia.

A randomized comparative trial of OTSC and Padlock for upper GI hemostasis in a standardized experimental setting.

INTRODUCTION: Upper gastrointestinal bleeding (UGIB) is the key emergency situation in clinical endoscopy and is traditionally treated with injection, thermal or through the scope clipping therapy. Mortality rates are in the range of 8-10% and demand new treatment approaches. The Over-The-Scope Clip (OTSC®) has been described as a very effective hemostatic device in UGIB. We compared OTSC with the Padlock™ device in an established pre-clinical setting. MATERIAL AND METHODS: Our test-bed consisted of the biohybrid EASIE model using soft silicone tubes, tunneled into the gastric wall and surfacing at a mucosa defect, representing the bleeding site. After successful deployment of the OTSC and Padlock devices on the spurting ulcer bleed (Forrest Ia) the vessel tubes were pressurized with a manometer to 120 mmHg. Tight closure at this pressure was defined as successful hemostasis (primary endpoint). N = 11 procedures were done with each device. Statistical testing was done using Fisher's exact test. Sample size was adjusted to an assumed α-error of 5% (two-sided test) and a power of 80%. RESULTS: Technically correct placement of the respective hemostatic device was achieved in all procedures. A statistically significant difference was found in the primary endpoint. In OTSC the success proportion was 100%; 11/11 (95% KI 74.1% to 100%); in Padlock it was 0%; 0/11 (95% KI 0%-25.8%). This means that no bleeding was stopped by Padlock. The mean value of perfusion pressure resistance was 300 mmHg (cut-off) for OTSC and 9.2 ± 8.4 mmHg for Padlock. DISCUSSION: Our data on hemostatic function of OTSC coincide with the clinical literature and earlier pre-clinical studies in the EASIE model, which is widely accepted as a realistic and effective simulation system for clinical conditions. The inability of Padlock to stop hemorrhage may be due to design differences and, thus, its limitation in providing tight sealing of the clipped tissue. CONCLUSION: Different types of endoscope-tip mounted clips have different performances. OTSC consistently stops simulated spurting bleeding, Padlock fails to do so. These differences are statistically significant.

International multicenter experience with an over-the-scope clipping device for endoscopic management of GI defects (with video).

BACKGROUND: The over-the-scope clip (OTSC) provides more durable and full-thickness closure as compared with standard clips. Only case reports and small case series have reported on outcomes of OTSC closure of GI defects. OBJECTIVE: To describe a large, multicenter experience with OTSCs for the management of GI defects. Secondary goals were to determine success rate by type of defect and type of therapy and to determine predictors of treatment outcomes. DESIGN: Multicenter, retrospective study. SETTING: Multiple, international, academic centers. PATIENTS: Consecutive patients who underwent attempted OTSC placement for GI defects, either as a primary or as a rescue therapy. INTERVENTIONS: OTSC placement to attempt closure of GI defects. MAIN OUTCOME MEASUREMENTS: Long-term success of the procedure. RESULTS: A total of 188 patients (108 fistulae, 48 perforations, 32 leaks) were included. Long-term success was achieved in 60.2% of patients during a median follow-up of 146 days. Rate of successful closure of perforations (90%) and leaks (73.3%) was significantly higher than that of fistulae (42.9%) (P < .05). Long-term success was significantly higher when OTSCs were applied as primary therapy (primary 69.1% vs rescue 46.9%; P = .004). On multivariate analysis, patients who had OTSC placement for perforations and leaks had significantly higher long-term success compared with those who had fistulae (OR 51.4 and 8.36, respectively). LIMITATIONS: Retrospective design and multiple operators with variable expertise with the OTSC device. CONCLUSION: OTSC is safe and effective therapy for closure of GI defects. Clinical success is best achieved in patients undergoing closure of perforations or leaks when OTSC is used for primary or rescue therapy. Type of defect is the best predictor of successful long-term closure.

Endoscopic full-thickness resection of submucosal gastric tumors.

BACKGROUND AND AIMS: Endoscopic full-thickness resection (EFTR) is a minimally invasive method for en bloc resection of gastrointestinal lesions, such as early cancer or submucosal tumor. The aim of this pilot study was to evaluate a novel EFTR prototype device for full-thickness resection of the gastric wall containing artificial submucosal lesions. METHODS: Six artificial submucosal tumors were surgically created in the gastric submucosa by implanting 8-mm cork beads in anesthetized pigs. EFTR of the lesions was attempted using a prototype device which consists of a large transparent plastic cap, loaded onto the tip of the endoscope, into which the submucosal lesion and the surrounding gastrointestinal wall can be pulled by using suction, a grasping forceps, or a dedicated anchoring device. An over-the-scope clip (OTSC) can be deployed underneath the submucosal lesion and a pre-loaded snare is used for EFTR above the OTSC. RESULTS: The median procedure time was 15 min (interquartile range 11-22). Successful resection of the artificial submucosal lesion was achieved in 4/6 (67%) cases. Successful EFTR of the gastric wall was achieved in 3/6 (50%) cases. In all cases, the OTSC closed the EFTR site completely. CONCLUSIONS: Gastric EFTR using the novel EFTR prototype device is feasible in a live animal model. The technique can achieve a full-thickness gastric wall and submucosal tumor resection with reliable closure of the gastric wall, but further refinements of the technique and device are necessary in order to reliably resect submucosal lesions, especially larger ones.

Endoscopic full-thickness resection in the colon by using a clip-and-cut technique: an animal study.

BACKGROUND: Although endoscopic resection techniques have been established for definitive therapy of mucosal neoplasia, complete histopathological assessment or resection of subepithelial lesions is not reliably possible. OBJECTIVE: To overcome these limitations, a novel endoscopic full-thickness resection (EFTR) and closure technique was developed. DESIGN: Animal survival study. ANIMALS: Eight female domestic pigs. INTERVENTIONS: Two-centimeter artificial distal colonic lesions were created endoscopically. EFTR of the lesions was attempted using a prototype device, which consists of a large transparent plastic cap with a preloaded snare and a modified over-the-scope clip. After the procedure, half of the animals were killed after 7 days, and the other half after 28 days. MAIN OUTCOME MEASUREMENTS: Complete resection (all markings included in the specimen), technical success, complication rates, and wound healing on follow-up autopsy and histology. RESULTS: EFTR of healthy colonic tissue was possible in all cases; 2 additional clips had to be placed for complete closure in 1 case. In 1 animal, the preloaded closure failed, and the animal was prematurely killed. All other animals had an uneventful postoperative course. Necropsy and histopathological evaluation demonstrated well-healed resection sites with no evidence of intra-abdominal infection or inadvertent organ inclusion. LIMITATIONS: Animal model, resection of healthy tissue. CONCLUSION: This novel device allows for reliable full-thickness resection and closure of 2-cm specimens of the colonic wall in a single procedure as well as reliable wound healing of EFTR defects.

The Over-The-Scope Clip (OTSC) for the treatment of gastrointestinal bleeding, perforations, and fistulas.

BACKGROUND: The Over-The-Scope Clip (OTSC(®)) enables the treatment of patients with gastrointestinal complications such as bleeding, perforations, and fistulas. The aim of this retrospective study was to analyze the therapeutic results of the performed treatments. METHODS: Since April 2006, 50 patients have been treated for different indications with the OTSC clip in our department. Besides hemostasis (n = 27) in the colon and the upper GI tract, the clip has been used for closure of esophageal and gastric perforations and adaptation of covered and free perforations after colonoscopy (n = 11). Furthermore, the OTSC has been used to close fistulas (n = 8) and for preoperative marking (n = 4). RESULTS: The primary treatment was successful in all cases. There were two secondary bleedings that required endoscopic interventions. Closure of iatrogenic perforations of the upper and lower GI tract was successful in all cases. A permanent closure of fistulas could not be achieved in all cases with the OTSC clip. CONCLUSION: The OTSC clip is effective and safe for complicated bleeding and closure of perforations of the gastrointestinal tract. Nevertheless, sufficient closure of chronic fistulas with the OTSC still remains an unsolved problem.

Endoluminal full-thickness resection of GI lesions: a new device and technique.

Full-thickness resection techniques are of growing interest in the field of endoscopic removal of tumors or their precursors in the digestive tract. A new dedicated full-thickness resection device has been developed based on the combination of the OTSC clip, an enlarged resection cap and an integrated snare. The device prototype allows combined resection of all gastrointestinal organ wall layers in one maneuver, up to a size of 3 x 3 cm. The device has been pre-clinically tested to demonstrate feasibility of full-thickness resection in the colon. Two clinical cases have been performed successfully to date.

Analysis on the healing of gastrointestinal ulceration by using Hemospray.

Healing of gastrointestinal ulcers after Hemospray application was reported in literature. The pathophysiological mechanism of action of hemostatic powders is not elucidated so far. A prospective animal model was performed to evaluate the effect of Hemospray application on the healing process of artificially induced ulcers of the upper and lower gastrointestinal tract. In 10 pigs, 20 ulcers were created in each the upper and the lower gastrointestinal tract by endoscopic mucosal resection. 50% of the pigs were immediately treated with Hemospray application, the others were not treated. Ulcer size was measured endoscopically on day 0, 2, and 7. On day 7 the ulcers were histopathological evaluated for capillary ingrowth and the thickness of the collagen layer. After 7 days the sizes of the ulcers decreased significantly (stomach: - 22.8% with Hemospray application, - 19% without Hemospray application; rectum: - 50.8% with Hemospray application, - 49.5% without Hemospray application; p = 0.005-0.037), but without significant difference between both groups. This study shows no significant effect of the hemostatic powder Hemospray on ulcer healing in the upper and lower gastrointestinal tract compared with untreated controls, neither harmful nor beneficial. However, some trends merit further trials in patients and may indicate a possible mechanism of accelerated mucosal healing.

The Use of the Over the Scope Clips Beyond Its Standard Use: A Pictorial Description.

Despite major improvements in endoscopic devices and therapeutic endoscopy, closure of gastrointestinal perforations, dehiscence, and fistulae had remained problematic. However, since the advent of devices such as the over the scope clip and others, endoscopic closure of gastrointestinal defects has become a routine approach. Furthermore, because of its strong apposition force, the over the scope clip may also be used to anchor fully covered self-expanding metal stents. In addition, the over the scope clip is an effective rescue therapy for various types of gastrointestinal bleeding pathologies. It is frequently used as an additional tool in complex gastrointestinal leak cases requiring internal and external drains.

Surgery of colorectal carcinoma in patients aged over 80.

BACKGROUND: The incidence of colorectal carcinoma increases rapidly in aged patients. We investigated retrospectively the differences in treatment relative to the patients' age. PATIENTS AND METHODS: A total of 394 patients with colorectal carcinoma (group I: > or =80 years, n = 197; group II: 60-79 years, n = 197) were analyzed in an average period of 4 years in relation to surgery, comorbidities, postoperative morbidity, mortality, survival and recurrence. RESULTS: Patients > or =80 years had a significantly higher rate of comorbid conditions (p = 0.04; cardiovascular, p = 0.01; diabetes mellitus, p < 0.05) and more carcinomas in the sigmoid/rectum (72% vs. 67%; p < 0.05). Tumor stage, R0 resection rate, and overall complication rate were not influenced by age. The 30-day mortality rate was significantly higher in group I (12% vs. 3%; p = 0.02). Emergency surgical procedures were required significantly more often in group I (14%) than in group II (5%; p = 0.003). The 5-year survival rate among patients in group I was 30.1% compared to 50.5% among patients in group II (p < 0.0001). CONCLUSIONS: Elderly patients have a higher rate of comorbidity and a higher postoperative 30-day mortality rate. Tumor stage, R0 resection rate, and overall postoperative complication rate do not appear to be influenced by age. The higher rate of emergency operations on patients > or =80 years is associated with the higher 30-day mortality. Even in patients aged > or =80 years, attention should focus on the long-term oncological results, after appropriate assessment of the preoperative risk.

Feasibility study for secure closure of natural orifice transluminal endoscopic surgery gastrotomies by using over-the-scope clips.

BACKGROUND: The secure sealing of natural orifice transluminal endoscopic surgery (NOTES) approaches to the abdominal cavity is a problem that has not been solved. The feasibility of closing iatrogenic endoscopic GI-tract perforations by using a new over-the-scope clip was recently described. OBJECTIVE: To demonstrate the feasibility of endoscopic closure of transgastric NOTES approaches with a novel clip system. DESIGN: Acute nonsurvival animal study (porcine model; n = 9). INTERVENTIONS: Transgastric approaches were performed by using a needle-knife and balloon dilation. After abdominopelvic exploration, the transgastric approaches were closed by using the OTSC clipping system with suction. The procedure was performed under laparoscopic visualization. RESULTS: Gastrotomy lesions could primarily be closed in 8 cases. However, the laparoscopic control indicated that the clip adaptation of the wound margins was not completely airtight under maximum insufflation of the stomach in 4 of 9 cases. LIMITATION: Nonsurvival animal study. CONCLUSIONS: Sufficient closure of transgastric NOTES approaches is feasible when using the OTSC system. When considering our clinical experience, the OTSC system was shown to be an uncomplicated and secure sealing technique in human beings.

Differential quantitative analysis of MHC ligands by mass spectrometry using stable isotope labeling.

Currently, no method allows direct and quantitative comparison of MHC-presented peptides in pairs of samples, such as transfected and untransfected, tumorous and normal or infected and uninfected tissues or cell lines. Here we introduce two approaches that use isotopically labeled reagents to quantify by mass spectrometry the ratio of peptides from each source. The first method involves acetylation and is both fast and simple. However, higher peptide recoveries and a finer sensitivity are achieved by the second method, which combines guanidination and nicotinylation, because the charge state of peptides can be maintained. Using differential acetylation, we identified a beta catenin-derived peptide in solid colon carcinoma overpresented on human leucocyte antigen-A (HLA-A)(*)6801. Guanidination/nicotinylation was applied to keratin 18-transfected cells and resulted in the characterization of the peptide RLASYLDRV (HLA-A(*)0201), exclusively presented on the transfectant. Thus, we demonstrate methods that enable a pairwise quantitative comparison leading to the identification of overpresented MHC ligands.

Indication for 'Over the scope' (OTS)-clip vs. covered self-expanding metal stent (cSEMS) is unequal in upper gastrointestinal leakage: results from a retrospective head-to-head comparison.

BACKGROUND: Intestinal perforation or leakage increases morbidity and mortality of surgical and endoscopic interventions. We identified criteria for use of full-covered, extractable self-expanding metal stents (cSEMS) vs. 'Over the scope'-clips (OTSC) for leak closure. METHODS: Patients who underwent endoscopic treatment for postoperative leakage, endoscopic perforation, or spontaneous rupture of the upper gastrointestinal tract between 2006 and 2013 were identified at four tertiary endoscopic centers. Technical success, outcome (e.g. duration of hospitalization, in-hospital mortality), and complications were assessed and analyzed with respect to etiology, size and location of leakage. RESULTS: Of 106 patients (male: 75 (71%), female: 31 (29%); age (mean ± SD): 62.5 ± 1.3 years, 72 (69%) were treated by cSEMS and 34 (31%) by OTSC. For cSEMS vs. OTSC, mean treatment duration was 41.1 vs. 25 days, p<0.001, leakage size 10 (1-50) vs. 5 (1-30) mm (median (range)), and complications were observed in 68% vs. 8.8%, p<0.001, respectively. Clinical success for primary interventional treatment was observed in 29/72 (40%) vs. 24/34 (70%, p = 0.006), and clinical success at the end of follow-up was 46/72 (64%) vs. 29/34 (85%) for patients treated by cSEMS vs. OTSC; p = 0.04. CONCLUSION: OTSC is preferred in small-sized lesions and in perforation caused by endoscopic interventions, cSEMS in patients with concomitant local infection or abscess. cSEMS is associated with a higher frequency of complications. Therefore, OTSC might be preferred if technically feasible. Indication criteria for cSEMS vs. OTSC vary and might impede design of randomized studies.

Treatment of liver transplant graft-versus-host disease with antibodies against tumor necrosis factor-α.

Acute graft-versus-host disease is uncommon after liver transplant. We recently treated a 60-year-old man with liver transplant for hepatocellular carcinoma. After the primary liver transplant graft did not function, revision liver transplant resulted in excellent function. Subsequently, the patient developed watery diarrhea, systemic inflammatory response syndrome, a skin rash on his limbs and trunk, and palmar erythema. Skin biopsy suggested viral exanthems consistent with cytomegalovirus. Despite treatment for cytomegalovirus, intestinal symptoms worsened. Analysis of peripheral blood with fluorescence-activated cell sorting showed a high proportion of T lymphocytes, with 5% to 10% T cells specific to the second donor, suggestive of graft-versus-host disease. Within 48 hours after beginning therapy with antibodies against tumor necrosis factor-α (infliximab), the skin rash disappeared and endoscopy showed slight improvement of the mucosal regeneration. However, despite antifungal prophylaxis with caspofungin, the patient developed angioinvasive pulmonary aspergillosis and multiple organ failure, and he died. In conclusion, typical clinical symptoms of graft-versus-host disease after liver transplant may include skin rash and gastrointestinal symptoms, and diagnosis may be confirmed by histologic examination and testing for blood chimerism. A consensus for the treatment of graft-versus-host disease still is lacking, but tumor necrosis factor-α is an encouraging target for therapy to decrease the symptoms of graft-versus-host disease and enable mucosal regeneration.