Outcomes of endoscopic ultrasound and endoscopic resection of gastrointestinal subepithelial lesions: a single-center retrospective cohort study.

BACKGROUND: Endoscopic resection (ER) is an emerging therapeutic alternative for subepithelial gastrointestinal lesions (SELs). We aimed to determine whether size, layer of origin, and histology based on endoscopic ultrasound (EUS) and EUS-guided sampling (EUS-GS) influenced the outcomes and selection of patients for ER. METHODS: We performed a retrospective review of patients who underwent EUS, EUS-GS and resection of SELs from 2012-2019. Two pathologists reviewed the histology and layer of origin of all resected specimens, serving as the criterion for EUS accuracy. RESULTS: Seventy-three patients were included, of whom 59 (81%) were gastric SELs. Per EUS, median lesion size was 21 mm (interquartile range 15-32), and 63 (86%) originated from the 4th layer. The overall accuracy of EUS and EUS-GS in predicting the layer of origin and histology was 88% (95% confidence interval [CI] 77-94%) and 96% (95%CI 87-98%), respectively. Based on EUS, 18 (25%) patients were referred for ER, 5 (7%) to laparoscopic-endoscopic cooperative surgery, and 50 (68%) to surgery. Size >20 mm was associated with the type of resection approach (P=0.005), while layer of origin and histology were not (P=0.06 and P=0.09, respectively). When SELs were inaccurately classified (n=4) there were no adverse events or revision of the resection approach. CONCLUSIONS: EUS plays an important role in the outcome of resection approach for SELs, with size significantly influencing the selection for ER. In patients undergoing ER, no revised resections were needed when EUS was inaccurate.

Randomized Phase II Trial of Polyphenon E versus Placebo in Patients at High Risk of Recurrent Colonic Neoplasia.

Polyphenon E (Poly E) is a green tea polyphenol preparation whose most active component is epigallocatechin gallate (EGCG). We studied the cancer preventive efficacy and safety of Poly E in subjects with rectal aberrant crypt foci (ACF), which represent putative precursors of colorectal cancers. Eligible subjects had prior colorectal advanced adenomas or cancers, and had ≥5 rectal ACF at a preregistration chromoendoscopy. Subjects (N = 39) were randomized to 6 months of oral Poly E (780 mg EGCG) daily or placebo. Baseline characteristics were similar by treatment arm (all P >0.41); 32 of 39 (82%) subjects completed 6 months of treatment. The primary endpoint was percent reduction in rectal ACF at chromoendoscopy comparing before and after treatment. Among 32 subjects (15 Poly E, 17 placebo), percent change in rectal ACF number (baseline vs. 6 months) did not differ significantly between study arms (3.7% difference of means; P = 0.28); total ACF burden was also similar (-2.3% difference of means; P = 0.83). Adenoma recurrence rates at 6 months were similar by arm (P > 0.35). Total drug received did not differ significantly by study arm; 31 (79%) subjects received ≥70% of prescribed Poly E. Poly E was well tolerated and adverse events (AE) did not differ significantly by arm. One subject on placebo had two grade 3 AEs; one subject had grade 2 hepatic transaminase elevations attributed to treatment. In conclusion, Poly E for 6 months did not significantly reduce rectal ACF number relative to placebo. Poly E was well tolerated and without significant toxicity at the dose studied. PREVENTION RELEVANCE: We report a chemoprevention trial of polyphenon E in subjects at high risk of colorectal cancer. The results show that polyphenon E was well tolerated, but did not significantly reduce the number of rectal aberrant crypt foci, a surrogate endpoint biomarker of colorectal cancer.

Efficacy of Difluoromethylornithine and Aspirin for Treatment of Adenomas and Aberrant Crypt Foci in Patients with Prior Advanced Colorectal Neoplasms.

Difluoromethylornithine (DFMO), an inhibitor of polyamine synthesis, was shown to act synergistically with a NSAID for chemoprevention of colorectal neoplasia. We determined the efficacy and safety of DFMO plus aspirin for prevention of colorectal adenomas and regression of rectal aberrant crypt foci (ACF) in patients with prior advanced adenomas or cancer. A double-blinded, placebo-controlled trial was performed in 104 subjects (age 46-83) randomized (1:1) to receive daily DFMO (500 mg orally) plus aspirin (325 mg) or matched placebos for one year. All polyps were removed at baseline. Adenoma number (primary endpoint) and rectal ACF (index cluster and total) were evaluated at a one year colonoscopy. ACF were identified by chromoendoscopy. Toxicity was monitored, including audiometry. Eighty-seven subjects were evaluable for adenomas or ACF modulation (n = 62). At one year of treatment, adenomas were detected in 16 (38.1%) subjects in the DFMO plus aspirin arm (n = 42) versus 18 (40.9%) in the placebo arm (n = 44; P = 0.790); advanced adenomas were similar (n = 3/arm). DFMO plus aspirin was associated with a statistically significant reduction in the median number of rectal ACF compared with placebo (P = 0.036). Total rectal ACF burden was also reduced in the treatment versus the placebo arm relative to baseline (74% vs. 45%, P = 0.020). No increase in adverse events, including ototoxicity, was observed in the treatment versus placebo arms. While adenoma recurrence was not significantly reduced by one year of DFMO plus aspirin, the drug combination significantly reduced rectal ACF number consistent with a chemopreventive effect.

A novel strategy to initiate a peroral endoscopic myotomy program.

OBJECTIVES: The standard of care for achalasia remains laparoscopic Heller myotomy with partial fundoplication. Peroral endoscopic myotomy (POEM) has been introduced as an alternative, but safety and long-term comparative efficacy are not yet established. We report our experience in developing a POEM program using a novel hybrid approach. METHODS: We developed a hybrid approach to POEM with a POEM followed by laparoscopic evaluation, extension of the myotomy, if necessary, and partial fundoplication. We reviewed the results of the programme from April 2012 until May 2015. Starting in 2014, we began offering patients stand-alone POEM. Patient data were collected. Preoperative and postoperative Eckardt scores were compared. RESULTS: A total of 28 patients underwent POEM or POEM plus laparoscopic evaluation with partial fundoplication. Patient characteristics and perioperative and postoperative data were recorded. The median preoperative Eckardt score was 6 (range 4-11). The mean follow-up period was 136 days (range 41-330) and the median postoperative Eckardt score was 0 (range 0-6) at 6 weeks. Of our initial 10 patients, 6 required laparoscopic extension of the myotomy; 7 subsequent patients did not require an additional myotomy. Three patients who underwent POEM without laparoscopy continued to have dysphagia postoperatively. One patient had an attempted POEM that was aborted secondary to bleeding, and a standard laparoscopic modified Heller myotomy with partial fundoplication was performed. CONCLUSIONS: The excellent results of laparoscopic myotomy with partial fundoplication are challenging to duplicate during the initial adoption of a POEM approach. We present a program developed to steepen the learning curve and enhance patient safety while implementing this new procedure.

A case report of sevelamer-associated recto-sigmoid ulcers.

BACKGROUND: Optimal phosphorous control is an important aspect of the care of patients with end-stage renal disease, and phosphate binders are usually needed. CASE PRESENTATION: A 74-year-old woman with end-stage renal disease on maintenance hemodialysis presented to the emergency room with abdominal discomfort, rectal pain, and blood-tinged stools. Initial concern was for a rectal carcinoma, based on the symptoms and imaging in initial computerized tomography of the abdomen showing rectal wall thickening, and her clinical presentation. She had been treated with the phosphate binder sevelamer for two months. In this case report, we explore the unique features of sevelamer-associated recto-sigmoid ulcers which led to her symptoms. CONCLUSION: Sevelamer is widely used in chronic kidney disease and end-stage renal disease patients with hyperphosphatemia. It is a crosslinked polymeric amine that binds phosphates and bile acids; it is not systemically absorbed. To the authors' knowledge, this is the first reported case of recto-sigmoid ulcers associated with use of this phosphate binder. Nephrologists, pathologists, and gastroenterology sub-specialists should be aware of this recently-reported entity in patients on sevelamer with suggestive symptoms, as this medication is widely used in renal patients.

NSAID enteropathy: appearance at CT and MR enterography in the age of multi-modality imaging and treatment.

CT and MR enterography and capsule endoscopy are increasingly used as routine diagnostic tests for patients with potential small bowel disorders and obscure gastrointestinal bleeding. Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used drugs that disrupt prostaglandin synthesis and result in a variety of localized complications within the small bowel ranging from ulcer formation to characteristic circumferential strictures, or diaphragms. NSAID enteropathy encompasses this spectrum of acute and chronic inflammatory sequelae, and is associated with typical findings at capsule endoscopy and surgery. Herein we review the typical clinical presentation of NSAID enteropathy, in addition to its endoscopic appearances, focusing on imaging findings at cross-sectional enterography. Multiple, short-segment strictures are the hallmarks of imaging diagnosis. Strictures may have minimal hyperenhancement or wall thickening, but these findings are typically symmetric and circumferential with respect to the bowel lumen. Multifocal Crohn's strictures, and occasionally radiation-induced strictures or adhesions, will mimic NSAID diaphragms. Multi-phase or multi-sequence imaging at CT and MR enterography increase diagnostic confidence in stricture presence. Strategies for subsequent workup and therapy after enterography are also discussed. Given the frequent use of NSAIDs and typical appearance of these strictures, knowledge of characteristic imaging findings can be particularly useful when evaluating patients with anemia and recurrent small bowel obstruction.

Adverse events related to colonic endoscopic mucosal resection and polypectomy.

Colonoscopy is a commonly performed procedure. The rate of adverse events is 2.8 per 1000 screening colonoscopies. These adverse events include cardiovascular and pulmonary events, abdominal pain, hemorrhage, perforation, postpolypectomy syndrome, infection, and death. Serious adverse events, such as hemorrhage and perforation, occur most frequently when colonoscopy is performed with polypectomy. This article highlights the prevention and management of adverse events associated with polypectomy and endoscopic mucosal resection of colonic lesions.

Achieving hemostasis and the risks associated with therapy.

Acute gastrointestinal bleeding is a common cause for hospitalization. Endoscopic hemostasis plays a central role in the management of lesions with active bleeding or high-risk stigmata for rebleeding. The efficacy and safety of endoscopic hemostasis rely on the identification of lesions suitable for endoscopic therapy, selection of the appropriate hemostatic devices, attention to technique, and prompt recognition and management of procedure-related adverse events. In this article, practical applications of hemostatic devices and pitfalls related to endoscopic hemostasis are discussed.

Emerging endoscopic therapies for nonvariceal upper gastrointestinal bleeding.

Several new devices and innovative adaptations of existing modalities have emerged as primary, adjunctive, or rescue therapy in endoscopic hemostasis of gastrointestinal hemorrhage. These techniques include over-the-scope clip devices, hemostatic sprays, cryotherapy, radiofrequency ablation, endoscopic suturing, and endoscopic ultrasound-guided angiotherapy. This review highlights the technical aspects and clinical applications of these devices in the context of nonvariceal upper gastrointestinal bleeding.

Feasibility of NOTES omental plug repair of perforated peptic ulcers: results from a clinical pilot trial.

BACKGROUND: Ulcer perforation carries up to a 30 % 1-year mortality rate. Intervention-related adverse events are among statistically significant predictors of 1-year mortality. A natural orifice transluminal endoscopic surgical (NOTES) approach may be less invasive and may decrease procedure-related adverse events by diminishing the so-called second hit, thus leading to decreased morbidity and mortality. We sought to assess the feasibility of an endoscopic transluminal omental plug technique in patients with perforated gastroduodenal ulcers under laparoscopic guidance. METHODS: Patients with suspected acute gastroduodenal ulcer perforations were offered participation in this prospective pilot study. Closure of the perforation was attempted using the NOTES omental plug technique. Demographic, clinical, endoscopic, and radiographic data were abstracted, as were data for morbidity, mortality, and pilot data regarding quality of life (QOL). RESULTS: From February 2010 through February 2012, a total of 17 patients presented to a tertiary care center with clinically suspected perforated ulcer. Of seven patients (mean age 79 years, range 64-89 years) who consented to the study, three underwent the study procedure. All patients had multiple comorbidities. Two patients presented with 4-6 mm perforated peptic ulcers and underwent successful laparoscopic-assisted NOTES omental and falciform ligament patch closure, respectively. Postoperative radiographic contrast studies showed no leak, and patients were discharged home on postoperative days 3 and 4. The third patient had undergone enterocutaneous fistula repair with herniorrhaphy 6 weeks before. Although a transluminal endoscopic approach was feasible, the omentum was under too much tension to be secured. This procedure was converted to an open omental patch repair. For all but one patient who provided consent, obtaining QOL data was feasible. CONCLUSIONS: Initial results from a laparoscopic-assisted NOTES approach for closure of perforated peptic ulcers appear promising and enable swift recovery in selected patients. This is especially important in elderly and/or immunocompromised patients. Technical details and patient selection criteria continue to evolve.

Stent-associated esophagorespiratory fistulas: incidence and risk factors.

BACKGROUND: Esophageal self-expandable stents (SESs) effectively treat strictures and leaks but may be complicated by a stent-associated esophagorespiratory fistula (SERF). Little is known about SERFs. OBJECTIVE: To determine the incidence, morbidity, mortality, and risk factors for SERF. DESIGN: Retrospective case-control study. SETTING: Single referral center. PATIENTS: All adults undergoing esophageal SES placement during a 10-year period. INTERVENTION: Stent placement. MAIN OUTCOME MEASUREMENTS: Occurrence of SERF, morbidity, and mortality. RESULTS: A total of 16 of 397 (4.0%) patients developed SERF at a median of 5 months after stent placement (range 0.4-53 months) including 6 of 94 (6%), 10 of 71 (14%), and 0 of 232 (0%) of those with lesions in the proximal, middle, and distal esophagus, respectively (overall P < .001). SERF occurred in 10% of those with proximal and mid-esophageal lesions, including 14% with benign strictures, 9% with malignant strictures, and none with other indications for SES placement (P = .27). The risk was highest (18%) in patients with benign anastomotic strictures. Risk factors for development of SERF included a higher Charlson comorbidity index score (odds ratio [OR] 1.47 for every 1-point increase; P = .04) and history of radiation therapy (OR 9.41; P = .03). Morbidity associated with SERF included need for lifelong feeding tubes in 11 of 22 (50%) and/or tracheostomy or mechanical ventilation in 5 of 22 (23%). Median survival after diagnosis was 4.5 months (range 0.35-67), and 7 patients survived less than 30 days. LIMITATIONS: Retrospective design, limited statistical power. CONCLUSION: SERF is a morbid complication of SES placement for strictures of the proximal and mid-esophagus. The dominant risk factors for development of SERF are prior radiation therapy and comorbidity score.

Novel approach to therapeutic ERCP after long-limb Roux-en-Y gastric bypass surgery using transgastric self-expandable metal stents: experimental outcomes and first human case study (with videos).

BACKGROUND: ERCP in Roux-en-Y gastric bypass (RYGB) patients is challenging. Balloon-assisted enteroscopy (BAE) allows access to the excluded stomach with creation of a percutaneous endoscopic gastrostomy (PEG). Transgastric self-expandable metal stent (SEMS) placement may allow antegrade ERCP in 1 session. OBJECTIVE: To determine the feasibility of transgastric endoscopy and ERCP through a newly created PEG augmented by SEMS placement. DESIGN: Prospective live animal study; human case report. SETTINGS: Animal laboratory and endoscopy units, tertiary care medical center. SUBJECTS: Nine domestic pigs; 1 patient. INTERVENTIONS: PEG tract with SEMS placement; transgastric endoscopy through SEMS. MAIN OUTCOME MEASUREMENTS: Technical success, feasibility of transgastric endoscopy. RESULTS: Successful SEMS deployment was achieved in 9 of 9 animals. The stent was removed in 6 animals; 3 were killed within 24 hours (group A) and 3 were killed 1 week later (group B). In 3 animals, stents remained in place, they were killed 9 to 15 days later (group C). Duodenoscopy was difficult in 1 animal from group A resulting in stent dislodgment. Peristomal infection occurred in 1 animal in group B. In group C, 1 stent was buried subcutaneously and 1 completely migrated out. Necropsy showed no peritoneal fluid or peritonitis in any animal. In the 1 patient, BAE-assisted PEG and SEMS placement in the excluded stomach allowed antegrade ERCP and biliary sphincterotomy without adverse events. LIMITATIONS: Small number of subjects. CONCLUSIONS: Performance of PEG with immediate SEMS placement allows for antegrade transgastric ERCP during 1 procedure. With the use of BAE, retrograde PEG/SEMS in excluded stomach allows therapeutic ERCP without need for surgery.

Use of Capsule Small Bowel Transit Time to Determine the Optimal Enteroscopy Approach.

BACKGROUND: Capsule small bowel transit time (SBTT) is used to select the most effective enteroscopy approach when targeting capsule endoscopy (CE) findings. Aim of this study was to determine if capsule SBTT can be used to guide the choice of enteroscopy technique for reaching CE abnormalities. METHODS: Single center, retrospective study involving 60 patients. Data were abstracted from medical records of patients with abnormal CE who proceeded to enteroscopy which included push enteroscopy (PE) single balloon enteroscopy (SBE) and double balloon enteroscopy (DBE). RESULTS: Ninety five findings were documented on CE with presumed identification of 56 (59%) of these abnormalities by enteroscopy. Majority were angioectasias on CE (42%) and enteroscopy (59%). Optimal cutoff values for selection of enteroscopy procedure were: 0-21% SBTT for PE (80% sensitivity, 74% specificity, 83% PPV); 0 - 36% SBTT for antegrade SBE (93% sensitivity, 40% specificity, 82% PPV); 0 - 57% SBTT for antegrade DBE (75% sensitivity, 80% specificity, 75% PPV); and 74 - 100% SBTT for retrograde DBE (88% sensitivity, 78% specificity, 78% PPV). CONCLUSION: Capsule SBTT may be used to guide the selection of enteroscopy approach. PE, antegrade SBE, antegrade DBE and retrograde DBE are optimal when abnormalities on CE are seen at ≤ 21%, ≤ 36%, ≤ 57% and ≥ 74% SBTT respectively.

External validation of the Glasgow-Blatchford Bleeding Score and the Rockall Score in the US setting.

BACKGROUND: The Glasgow-Blatchford Bleeding Score (GBS) and Rockall Score (RS) are clinical decision rules that risk stratify emergency department (ED) patients with upper gastrointestinal bleeding (UGIB). We evaluated GBS and RS to determine the extent to which either score identifies patients with UGIB who could be safely discharged from the ED. METHODS: We reviewed and extracted data from the electronic medical records of consecutive adult patients who presented with signs or symptoms of UGIB (hematemesis and/or melena) to an academic ED from April 1, 2004, to April 1, 2009. The primary outcome was need for intervention (blood transfusion and/or endoscopic/surgical intervention) or death within 30 days. RESULTS: We identified 171 patients with the following characteristics: mean age of 69.9 years (SD, 17.0 years ), 52% women, 20% with a history of liver disease, and 22% with history of gastrointestinal bleeding. Ninety (52.6%, 95% confidence interval, 44.9-60.3) patients had the primary outcome. GBS outperformed pre-endoscopy RS [area under the receiver operating characteristic curve (AUC)=0.79 vs 0.62; P=.0001; absolute difference, 0.17]. The prognostic accuracy of GBS and post-endoscopy RS was similarly high (AUC, 0.79 vs 0.72; P=.26; absolute difference, 0.07). The specificity of GBS and RS was suboptimal at all potential decision thresholds. CONCLUSIONS: Although GBS outperformed pre-endoscopy RS, the prognostic accuracy of GBS and post-endoscopy RS was similarly high. The specificity of GBS and RS was insufficient to recommend use of either score in clinical practice.