Joint Asian Pacific Association of Gastroenterology (APAGE)-Asian Pacific Society of Digestive Endoscopy (APSDE) clinical practice guidelines on the use of non-invasive biomarkers for diagnosis of colorectal neoplasia.

Screening for colorectal cancer (CRC) is effective in reducing CRC related mortality. Current screening methods include endoscopy based and biomarker based approaches. This guideline is a joint official statement of the Asian Pacific Association of Gastroenterology (APAGE) and the Asian Pacific Society of Digestive Endoscopy (APSDE), developed in response to the increasing use of, and accumulating supportive evidence for the role of, non-invasive biomarkers for the diagnosis of CRC and its precursor lesions. A systematic review of 678 publications and a two stage Delphi consensus process involving 16 clinicians in various disciplines was undertaken to develop 32 evidence based and expert opinion based recommendations for the use of faecal immunochemical tests, faecal based tumour biomarkers or microbial biomarkers, and blood based tumour biomarkers for the detection of CRC and adenoma. Comprehensive up-to-date guidance is provided on indications, patient selection and strengths and limitations of each screening tool. Future research to inform clinical applications are discussed alongside objective measurement of research priorities. This joint APAGE-APSDE practice guideline is intended to provide an up-to-date guide to assist clinicians worldwide in utilising non-invasive biomarkers for CRC screening; it has particular salience for clinicians in the Asia-Pacific region.

Efficacy and Safety of a Novel Hemostatic Peptide Solution During Endoscopic Submucosal Dissection: A Multicenter Randomized Controlled Trial.

INTRODUCTION: To compare the effectiveness of the novel hemostatic peptide, TDM-621, with that of conventional hemostatic methods in treating intraoperative blood oozing during endoscopic submucosal dissection (ESD). METHODS: This multicenter, open-label, randomized controlled trial involved 227 patients with gastric and rectal epithelial tumors in whom ESD was indicated. Patients in whom the source of blood oozing was difficult to identify with waterjet washing during the procedure and required hemostasis with hemostatic forceps were randomly assigned to the TDM-621 and control groups. The TDM-621 group (in which hemostasis was achieved with TDM-621, followed by coagulation hemostasis with hemostatic forceps, as needed) was compared with the control group (in which hemostasis was achieved with hemostatic forceps). The primary end point was the mean number of coagulations with hemostatic forceps, determined by a blinded independent review committee. The secondary end points were the rate of achievement of hemostasis with only TDM-621, the dosage of TDM-621, and adverse events in the TDM-621 group. RESULTS: The mean number of coagulations with hemostatic forceps was significantly reduced in the TDM-621 group (1.0 ± 1.4) compared with that in the control group (4.9 ± 5.2) ( P < 0.001). The rate of hemostasis achievement with only TDM-621 was 62.2%; the mean dosage of TDM-621 was 1.75 ± 2.14 mL. The rates of grade ≥3 adverse events were 6.2% and 5.0% in the TDM-621 and control groups, respectively. DISCUSSION: TDM-621 is a useful, easily operable hemostatic peptide for treatment of blood oozing during gastric and rectal ESD, with no serious safety concerns.

Benefits and challenges in implementation of artificial intelligence in colonoscopy: World Endoscopy Organization position statement.

The number of artificial intelligence (AI) tools for colonoscopy on the market is increasing with supporting clinical evidence. Nevertheless, their implementation is not going smoothly for a variety of reasons, including lack of data on clinical benefits and cost-effectiveness, lack of trustworthy guidelines, uncertain indications, and cost for implementation. To address this issue and better guide practitioners, the World Endoscopy Organization (WEO) has provided its perspective about the status of AI in colonoscopy as the position statement. WEO Position Statement: Statement 1.1: Computer-aided detection (CADe) for colorectal polyps is likely to improve colonoscopy effectiveness by reducing adenoma miss rates and thus increase adenoma detection; Statement 1.2: In the short term, use of CADe is likely to increase health-care costs by detecting more adenomas; Statement 1.3: In the long term, the increased cost by CADe could be balanced by savings in costs related to cancer treatment (surgery, chemotherapy, palliative care) due to CADe-related cancer prevention; Statement 1.4: Health-care delivery systems and authorities should evaluate the cost-effectiveness of CADe to support its use in clinical practice; Statement 2.1: Computer-aided diagnosis (CADx) for diminutive polyps (≤5 mm), when it has sufficient accuracy, is expected to reduce health-care costs by reducing polypectomies, pathological examinations, or both; Statement 2.2: Health-care delivery systems and authorities should evaluate the cost-effectiveness of CADx to support its use in clinical practice; Statement 3: We recommend that a broad range of high-quality cost-effectiveness research should be undertaken to understand whether AI implementation benefits populations and societies in different health-care systems.

Cost-effectiveness analysis of endoscopic resection for colorectal laterally spreading tumors: Endoscopic submucosal dissection versus piecemeal endoscopic mucosal resection.

OBJECTIVES: The cost-effectiveness of endoscopic submucosal dissection (ESD) and piecemeal endoscopic mucosal resection (pEMR) for colorectal laterally spreading tumors (LSTs) remains unclear. We examined the cost-effectiveness of these procedures for cases of colon/rectal LST-non-granular-type ≥2 cm and LST-granular-mixed-type ≥3 cm. METHODS: We performed a simulation model analysis using parameters based on clinical data from the National Cancer Center Hospital, Tokyo, and previous literature. The number of recurrences and surgeries and the required costs for 5 years following ESD and pEMR were assessed. Japanese cost data were used in the base-case analysis, and probabilistic sensitivity analysis (PSA) was performed. The Swedish cost data were used in the scenario analysis. RESULTS: Endoscopic submucosal dissection yielded a considerably lower number of recurrences and surgeries but required a higher cost than pEMR. The recurrence rates following ESD and pEMR were 0.9-1.3% and 21.1-25.9%, respectively. The incremental cost-effectiveness ratios for an avoided recurrence and surgery for ESD against pEMR were 376,796-476,496 JPY (3575-4521 USD) and 7,335,436-8,187,476 JPY (69,604-77,689 USD), respectively. PSA demonstrated that the probability of ESD being chosen as a more cost-effective option than pEMR was >50% at willingness-to-pay values of ≥400,000-500,000 JPY (3795-4744 USD) for avoiding a recurrence and ≥9,500,000-10,500,000 JPY (90,143-99,631 USD) for avoiding a surgery. In the scenario analysis, the required cost was also lower for ESD. CONCLUSIONS: Our findings suggest potentially favorable cost-effectiveness of ESD, depending on cost settings and the willingness-to-pay value for avoiding recurrence/surgery.

Clinical usefulness of red dichromatic imaging in hemostatic treatment during endoscopic submucosal dissection: First report from a multicenter, open-label, randomized controlled trial.

OBJECTIVES: To verify the efficacy and safety of red dichromatic imaging (RDI) in hemostatic procedures during endoscopic submucosal dissection (ESD). METHODS: This is a multicenter randomized controlled trial of 404 patients who underwent ESD of the esophagus, stomach, colorectum. Patients who received hemostatic treatments by RDI during ESD were defined as the RDI group (n = 204), and those who received hemostatic treatments by white light imaging (WLI) were defined as the WLI group (n = 200). The primary endpoint was a shortening of the hemostasis time. The secondary endpoints were a reduction of the psychological stress experienced by the endoscopist during the hemostatic treatment, a shortened treatment time, and a non-inferior perforation rate, in RDI versus WLI. RESULTS: The mean hemostasis time in RDI (n = 860) was not significantly shorter than that in WLI (n = 1049) (62.3 ± 108.1 vs. 56.2 ± 74.6 s; P = 0.921). The median hemostasis time was significantly longer in RDI than in WLI (36.0 [18.0-71.0] vs. 28.0 [14.0-66.0] s; P = 0.001) in a sensitivity analysis. The psychological stress was significantly lower in RDI than in WLI (1.71 ± 0.935 vs. 2.03 ± 1.038; P < 0.001). There was no significant difference in the ESD treatment time between RDI (n = 161) and WLI (n = 168) (58.0 [35.0-86.0] vs. 60.0 [38.0-88.5] min; P = 0.855). Four perforations were observed, but none of them took place during the hemostatic treatment. CONCLUSIONS: Hemostatic treatment using RDI does not shorten the hemostasis time. RDI, however, is safe to use for hemostatic procedures and reduces the psychological stress experienced by endoscopists when they perform hemostatic treatment during ESD. UMIN000025134.

Approaches for stricture prevention after esophageal endoscopic resection.

BACKGROUND AND AIMS: Endoscopic resection of extensive esophageal lesions has become more common as endoscopic resection techniques and equipment have developed. However, extensive esophageal endoscopic resections can cause postoperative esophageal strictures, which have a negative impact on the quality of life of patients. We aimed to review current treatments and innovative approaches to prevent esophageal strictures after widespread endoscopic resection of esophageal lesions. METHODS: We performed a comprehensive literature search from 2000 to 2016 using predetermined search terms to identify relevant articles and summarized their results as a narrative review. RESULTS: A total of 21 original articles and case series were identified. A circumferential mucosal defect involving more than three fourths of the esophageal luminal circumference was the primary risk factor for developing an esophageal stricture after endoscopic resection. Oral and injectable steroid therapy demonstrated promise in preventing post-endoscopic submucosal dissection esophageal strictures, with both strategies significantly reducing the number of required endoscopic balloon dilations. More data are needed on prophylactic self-expandable metal stents, local botulinum toxin injection, and oral tranilast as a strategy to prevent post-endoscopic submucosal dissection esophageal strictures. Although preliminary studies of tissue-shielding resection sites with polyglycolic acid sheets and fibrin glue and autologous cell sheet transplantation have demonstrated promising results, additional larger validation studies are needed. CONCLUSIONS: Oral and locally injected/administered steroids are first-line options for the prevention of esophageal strictures, but additional innovative solutions are being developed.

Efficacy of endoscopic mucosal resection with circumferential incision for patients with large colorectal tumors.

BACKGROUND & AIMS: Treatment of large colorectal neoplasms (>20 mm in diameter) by conventional endoscopic mucosal resection (EMR) often results in piecemeal resection that requires further intervention. We evaluated the efficacy of EMR with circumferential incision (CEMR). METHODS: From March 2008-July 2009, we resected 24 large colorectal neoplasms measuring 20-40 mm in diameter by using the CEMR technique. CEMR was performed by using a ball-tip bipolar needle knife with a snaring technique. After the injection of glycerol into the submucosal layer, a circumferential incision was made, and the neoplasm was resected by snaring. All lesions that showed a noninvasive pattern were diagnosed by magnifying chromoendoscopy as adenomas or intramucosal or submucosal superficial cancers. The number of en bloc resections and complications and the overall procedure time were determined. RESULTS: The proportions of en bloc and 2-piece resections by CEMR were 67% (16/24) and 17% (4/24), respectively. The median (interquartile range) time for CEMR completion was 40 minutes (30-63 minutes). No postsurgery complications occurred in any patient. CONCLUSIONS: CEMR might provide acceptable clinical outcomes for patients with large colorectal neoplasms. It results in a low incidence of incomplete treatments and low risk of complications.

Cancer prevention by bovine lactoferrin: from animal studies to human trial.

Colorectal cancer (CRC) is one of the most frequently diagnosed cancers and, despite improved colonoscopic screening, CRC is a leading cause of death from cancer. Administration of bovine lactoferrin (bLF) suppresses carcinogenesis in the colon and other organs of test animals, and recently it was shown that ingestion of bLF inhibits the growth of adenomatous polyps in human patients. Here we review work which established bLF as an anti-carcinogenic agent in laboratory animals and the results of a clinical trial which demonstrated that bLF can reduce the risk of colon carcinogenesis in humans.

Clinical Guidelines for Diagnosis and Management of Juvenile Polyposis Syndrome in Children and Adults­Secondary Publication

Juvenile polyposis syndrome (JPS) is a rare disease characterized by multiple hamartomatous polyps within the gastrointestinal tract. SMAD4 or BMPR1A is known as a causative gene of JPS. Approximately 75% of newly diagnosed cases have an autosomal-dominantly inherited condition, whereas 25% are sporadic without previous history of polyposis in the family pedigree. Some patients with JPS develop gastrointestinal lesions in childhood and require continuous medical care until adulthood. JPS is classified into three categories according to phenotypic features of polyp distributions, including generalized juvenile polyposis, juvenile polyposis coli, and juvenile polyposis of the stomach. Juvenile polyposis of the stomach is caused by germline pathogenic variants of SMAD4 with a high risk leading to gastric cancer. Pathogenic variants of SMAD4 are also associated with hereditary hemorrhagic telangiectasia-JPS complex, inducing regular cardiovascular survey. Despite growing concerns regarding the managing JPS in Japan, there are no practical guidelines. To address this situation, the guideline committee was organized by the Research Group on Rare and Intractable Diseases granted by the Ministry of Health, Labor and Welfare involving specialists from multiple academic societies. The present clinical guidelines explain the principles in the diagnosis and management of JPS with three clinical questions and corresponding recommendations based on a careful review of the evidence and involve incorporating the concept of the Grading of Recommendations, Assessment, Development, and Evaluation system. Herein, we present the clinical practice guidelines of JPS to promote seamless implementation of accurate diagnosis and appropriate management of pediatric, adolescent, and adult patients with JPS.