Valuing innovative endoscopic techniques: prophylactic clip closure after endoscopic resection of large colon polyps.

BACKGROUND AND AIMS: Clip closure of the mucosal defect after resecting large (≥20 mm) nonpedunculated colorectal polyps reduces postprocedure bleeding and is cost saving for payers. Clip costs are not reimbursed by payers, posing a major barrier to adoption of this technique in the community. We aimed to determine appropriate clip costs to support broader use of this procedure in practice. METHODS: We performed budget impact analysis using our recent decision analytic model, comparing prophylactic clip closure with no clip closure on national cost and outcomes data, to determine the maximum feasible clip price while maintaining cost savings in practice. Sensitivity analyses were performed on important clinical factors. RESULTS: In the original model, the baseline postprocedure bleeding risk was 6.8%, increasing cost of care by $614.11 averaged among all patients undergoing large polyp resection without clip closure. Prophylactic clip closure of only large right-sided polyps reduced postprocedure bleeding risk by 70.7% but resulted in cost saving only if the price of clips was $100 or less. Comparatively, prophylactic clip closure of large left-sided polyps had no clinical benefit and was not cost saving. Clip closure strategies focused only on extra-large polyps (≥40 mm), or patients taking antithrombotics regardless of polyp characteristics, were only minimally cost saving. Cost savings and maximum tolerated clip prices depended on medical comorbidity, which directly influences the costs of care to manage postprocedure bleeding. CONCLUSIONS: Prophylactic clip closure after endoscopic resection of large colon polyps, particularly those in the right colon segment, is cost saving but requires clip costs less than $100. Translating these findings into practice requires gastroenterology practices to obtain reimbursement from payers for improved clinical outcomes and to align commercial clip prices with this clinical indication.

Valuing innovative endoscopic techniques: endoscopic suturing to prevent stent migration for benign esophageal disease.

BACKGROUND AND AIMS: Reimbursement often presents a significant barrier to widespread adoption of innovative endoscopic devices. We aimed to determine the value (defined as cost savings to a payer) of endoscopic suturing devices in preventing the migration of esophageal stents placed for benign esophageal diseases. METHODS: A decision-analytic model was constructed from a payer perspective evaluating fully covered metal stent placement for benign esophageal diseases (fistula, leak, perforation, or stricture) in a hospital outpatient setting. The model compared 2 strategies: endoscopic suturing to anchor the stent or no suture. Health care outcomes and costs were derived from published systematic reviews and national databases (U.S. Food and Drug Administration Manufacturer and User Facility Device Experience [MAUDE] for safety data; 2018 Medicare Physician Fee Schedule and Provider Utilization and Payment Data databases for reimbursement data). RESULTS: From a payer perspective, reimbursement for care increased by US$1487.98 without endoscopic suturing per patient, compared with US$621.06 with endoscopic suturing, to cover the risk of stent migration in addition to usual professional and facility reimbursement for stent placement. Thus, an average cost saving of US$866.92 per patient was achieved with endoscopic suturing to reduce stent migration risks. Cost savings associated with suturing ranged from US$147.48 to US$1586.36 per patient, based on the indication for the procedure in sensitivity analysis. Cost savings increased with higher rates of technical success in suture placement. CONCLUSIONS: Creating a defined reimbursement pathway for endoscopic suture fixation of a stent for the treatment of benign esophageal diseases appears to be justified from a payer perspective.

A Review of Prevention of Post-ERCP Pancreatitis.

Endoscopic retrograde cholangiopancreatography (ERCP) is a diagnostic and therapeutic procedure employed in the management of disorders of the biliary system. Post-ERCP pancreatitis (PEP) is the most common complication of ERCP and can lead to significant morbidity as well as occasional mortality. In addition to adequate procedural training, therapeutic endoscopists who perform ERCPs should possess a thorough understanding of patient- and procedure-related risk factors for PEP. This knowledge can inform patient selection for ERCP and allow for appropriate management efforts to be performed in high-risk cases. Procedural techniques promoting minimally traumatic biliary cannulation should be employed when initial standard techniques are unsuccessful. In high-risk patients, several measures can be undertaken to limit the risk of PEP, including administration of rectal nonsteroidal anti-inflammatory drugs, prophylactic placement of pancreatic duct stents, and liberal administration of lactated Ringer solution. When PEP does occur, appropriate management with aggressive intravenous hydration, pain control, and early enteral nutrition should be administered. Additional research is needed to further define risk factors for PEP, optimal procedural techniques used during ERCP, and ideal prevention and treatment strategies to limit the incidence and severity of PEP in patients.

Gastric Adenocarcinoma: A Multimodal Approach.

Despite its declining incidence, gastric cancer (GC) remains a leading cause of cancer-related deaths worldwide. A multimodal approach to GC is critical to ensure optimal patient outcomes. Pretherapy fine resolution contrast-enhanced cross-sectional imaging, endoscopic ultrasound and staging laparoscopy play an important role in patients with newly diagnosed ostensibly operable GC to avoid unnecessary non-therapeutic laparotomies. Currently, margin negative gastrectomy and adequate lymphadenectomy performed at high volume hospitals remain the backbone of GC treatment. Importantly, adequate GC surgery should be integrated in the setting of a multimodal treatment approach. Treatment for advanced GC continues to expand with the emergence of additional lines of systemic and targeted therapies.

Gastric antral webs in adults: A case series characterizing their clinical presentation and management in the modern endoscopic era.

AIM: To investigate the current management of gastric antral webs (GAWs) among adults and identify optimal endoscopic and/or surgical management for these patients. METHODS: We reviewed our endoscopy database seeking to identify patients in whom a GAW was visualized among 24640 esophagogastroduodenoscopies (EGD) over a seven-year period (2006-2013) at a single tertiary care center. The diagnosis of GAW was suspected during EGD if aperture size of the antrum did not vary with peristalsis or if a "double bulb" sign was present on upper gastrointestinal series. Confirmation of the diagnosis was made by demonstrating a normal pylorus distal to the GAW. RESULTS: We identified 34 patients who met our inclusion criteria (incidence 0.14%). Of these, five patients presented with gastric outlet obstruction (GOO), four of whom underwent repeated sequential balloon dilations and/or needle-knife incisions with steroid injection for alleviation of GOO. The other 29 patients were incidentally found to have a non-obstructing GAW. Age at diagnosis ranged from 30-87 years. Non-obstructing GAWs are mostly incidental findings. The most frequently observed symptom prompting endoscopic work-up was refractory gastroesophageal reflux (n = 24, 70.6%) followed by abdominal pain (n = 11, 33.4%), nausea and vomiting (n = 9, 26.5%), dysphagia (n = 6, 17.6%), unexplained weight loss, (n = 4, 11.8%), early satiety (n = 4, 11.8%), and melena of unclear etiology (n = 3, 8.82%). Four of five GOO patients were treated with balloon dilation (n = 4), four-quadrant needle-knife incision (n = 3), and triamcinolone injection (n = 2). Three of these patients required repeat intervention. One patient had a significant complication of perforation after needle-knife incision. CONCLUSION: Endoscopic intervention for GAW using balloon dilation or needle-knife incision is generally safe and effective in relieving symptoms, however repeat treatment may be needed and a risk of perforation exists with thermal therapies.

Does Better Specimen Orientation and a Simplified Grading System Promote More Reliable Histologic Interpretation of Serrated Colon Polyps in the Community Practice Setting? Results of a Nationwide Study.

INTRODUCTION: Colonoscopic surveillance guidelines for serrated polyps (SPs) are predicated upon the histologic characteristics of the index polyp. However, discrimination between SP subtypes [hyperplastic polyps vs. sessile serrated adenoma/polyps (SSA/P)] is often unreliable. MATERIALS AND METHODS: We studied the impact of (1) a novel tissue orientation method, performed in the endoscopy laboratory, whereby polyps are flattened in a small paper envelope immediately after resection (modified protocol); and (2) 2012 consensus-modified criteria (CM-2012). These interventions were compared with conventional tissue-handling protocol (CP) and traditional 2008 World Health Organization criteria (WHO). Twenty blinded community pathologists from around the United States scored 100, independent, 0.5 to 2.0 cm, proximal colonic SPs randomly selected from a 2-site tissue section archive. We compared interobserver agreement and diagnostic grading. RESULTS: Interobserver agreement was higher using CM-2012 than WHO criteria (absolute agreement: 13% vs. 4%, P<0.01; 75% agreement: 54% vs. 38%, P<0.01). Interobserver agreement was higher with the modified protocol than with CP (WHO absolute agreement: 6% vs. 2%, P>0.05; WHO 75% agreement: 46% vs. 30%, P>0.05, and CM-2012 absolute agreement: 20% vs. 6%, P=0.07; CM-2012 75% agreement: 66% vs. 42%, P=0.03). Compared with WHO, use of CM-2012 criteria resulted in fewer diagnoses of "indeterminate"; more diagnoses of SSA/P (P<0.01); and "upgraded" the diagnosis from hyperplastic polyps to SSA/P in approximately 7% of cases. These observations were independent of polyp size, patient gender, and study site. CONCLUSIONS: Simple enhancements to postresection SP handling and diagnostic criteria markedly improve interobserver agreement of SP diagnosis among nongastrointestinal community pathologists. This finding, if confirmed, has important implications for SP colonoscopy surveillance guidelines.

Enoxaparin-Induced Liver Injury: Case Report and Review of the Literature and FDA Adverse Event Reporting System (FAERS).

Anticoagulants are a well known cause of drug-induced liver injury (DILI). We recently encountered a 45-year-old male who developed DILI during treatment with enoxaparin, a low-molecular-weight heparin (LMWH), for dural venous thrombosis. The man received enoxaparin 80 mg subcutaneously, twice daily. After 4 days, the patient was asymptomatic but he developed liver aminotransferase elevations: AST 340 U/L and ALT 579 U/L. Investigation revealed an R ratio of 19.9 by day 5 and a Roussel Uclaf Causality Assessment Method score of 10, giving a high probable likelihood that enoxaparin was the cause of hepatic injury. Enoxaparin was discontinued on day 7, and 1 week later AST and ALT had decreased to 61 and 273 U/L, respectively. This case prompted a literature search and a review of the FDA Adverse Event Reporting System (FAERS) database for the range of hepatic adverse events (HAEs) associated with this class. A MEDLINE/PubMed search was conducted using DILI terms and cross-referenced with the anticoagulant classes. A Freedom of Information Act (FOIA) request was also made to identify adverse events (AEs) associated with enoxaparin in FAERS. Case type, severity of outcome, and demographic information were analyzed. Five publications have reported DILI with enoxaparin. Trial data found elevations in ALT >3 times the upper limit of normal (ULN) for unfractionated heparins (UFH) and LMWH in 8 and 4-13 % of subjects, respectively. However, liver injury in all cases was mild, self-limited, and asymptomatic. Our FOIA request yielded 8336 adverse events related to enoxaparin over a 14-year period (Jan 2000-Sept 2014). Specific HAEs were found in 4 % of reports, but all were described with other serious adverse events. The reported outcomes of hospitalization (75 %), death (17 %), and life-threatening medical events (5 %) were likely due to other related serious adverse events such as hemorrhage (28 %) and thrombocytopenia (11 %). We conclude that LMWH-related liver injury is uncommon and reversible. The mechanism of liver injury is not known, although an idiosyncratic effect is postulated. Although the FAERS database lists hepatic injury in 4 % of all enoxaparin-related AEs, it appears that serious outcomes are related to non-hepatic events.

A simple tissue-handling technique performed in the endoscopy suite improves histologic section quality and diagnostic accuracy for serrated polyps.

BACKGROUND AND STUDY AIMS: Surveillance intervals after colonoscopic resection of serrated polyps are partially predicated on the histology of the polyp(s) removed during the index exam. Histologic discrimination between sessile serrated adenomas/polyps (SSA/P) and hyperplastic polyps is challenging. We devised and tested a simple tool--an envelope--that gastroenterologists can integrate into routine colonoscopy practice to address this problem. METHODS: In the "modified protocol," immediately after polypectomy each serrated polyp was flattened and enclosed in a paper envelope before being placed in formalin. In the pathology laboratory, each polyp was sectioned after processing. A two-site, prospective, randomized, single-blinded trial was performed to compare this modified protocol with the conventional protocol. Serrated polyps located proximal to the splenic flexure and 5-20 mm in diameter were included. A novel orientation score that measured the number of well-oriented crypts per unit area of polyp (higher orientation score = better orientation) was validated. Orientation score, SSA/P diagnosis rate, and inter-pathologist agreement were measured. RESULTS: A total of 375 polyps were enrolled, of which 264 were identified for analysis. The mean orientation scores in the modified and conventional protocol groups were 3.11 and 1.13, respectively (P < 0.0001). SSA/Ps were diagnosed in 103/135 cases (76.3%) in the modified protocol group vs. 54/129 (41.9%) in the conventional protocol group (P < 0.0001). Inter-pathologist agreement was higher with the modified than the conventional protocol (77.0% vs. 62.8%; P = 0.015). CONCLUSION: Standard polyp handling techniques may be sub-optimal for interpretation of serrated polyps resected at colonoscopy, and may lead to inadvertent histologic "under-grading" of many lesions. Our intervention improved histopathologic interpretation and increased the SSA/P diagnosis rate.

Identification of a novel deletion mutant strain in Saccharomyces cerevisiae that results in a microsatellite instability phenotype.

The DNA mismatch repair (MMR) pathway corrects specific types of DNA replication errors that affect microsatellites and thus is critical for maintaining genomic integrity. The genes of the MMR pathway are highly conserved across different organisms. Likewise, defective MMR function universally results in microsatellite instability (MSI) which is a hallmark of certain types of cancer associated with the Mendelian disorder hereditary nonpolyposis colorectal cancer. (Lynch syndrome). To identify previously unrecognized deleted genes or loci that can lead to MSI, we developed a functional genomics screen utilizing a plasmid containing a microsatellite sequence that is a host spot for MSI mutations and the comprehensive homozygous diploid deletion mutant resource for Saccharomyces cerevisiae. This pool represents a collection of non-essential homozygous yeast diploid (2N) mutants in which there are deletions for over four thousand yeast open reading frames (ORFs). From our screen, we identified a deletion mutant strain of the PAU24 gene that leads to MSI. In a series of validation experiments, we determined that this PAU24 mutant strain had an increased MSI-specific mutation rate in comparison to the original background wildtype strain, other deletion mutants and comparable to a MMR mutant involving the MLH1 gene. Likewise, in yeast strains with a deletion of PAU24, we identified specific de novo indel mutations that occurred within the targeted microsatellite used for this screen.

A composite of multiple signals distinguishes causal variants in regions of positive selection.

The human genome contains hundreds of regions whose patterns of genetic variation indicate recent positive natural selection, yet for most the underlying gene and the advantageous mutation remain unknown. We developed a method, composite of multiple signals (CMS), that combines tests for multiple signals of selection and increases resolution by up to 100-fold. By applying CMS to candidate regions from the International Haplotype Map, we localized population-specific selective signals to 55 kilobases (median), identifying known and novel causal variants. CMS can not just identify individual loci but implicates precise variants selected by evolution.