Endoscopic Removal of Premalignant Lesions Reduces Long-Term Colorectal Cancer Risk: Results From the Japan Polyp Study.

BACKGROUND & AIMS: To date, no regional evidence of long-term colorectal cancer (CRC) risk reduction after endoscopic premalignant lesion removal has been established. We aimed to analyze this over a long-term follow-up evaluation. METHODS: This was a prospective cohort study of participants from the Japan Polyp Study conducted at 11 Japanese institutions. Participants underwent scheduled follow-up colonoscopies after a 2-round baseline colonoscopy process. The primary outcome was CRC incidence after randomization. The observed/expected ratio of CRC was calculated using data from the population-based Osaka Cancer Registry. Secondary outcomes were the incidence and characteristics of advanced neoplasia (AN). RESULTS: A total of 1895 participants were analyzed. The mean number of follow-up colonoscopies and the median follow-up period were 2.8 years (range, 1-15 y) and 6.1 years (range, 0.8-11.9 y; 11,559.5 person-years), respectively. Overall, 4 patients (all males) developed CRCs during the study period. The observed/expected ratios for CRC in all participants, males, and females, were as follows: 0.14 (86% reduction), 0.18, and 0, respectively, and 77 ANs were detected in 71 patients (6.1 per 1000 person-years). Of the 77 ANs detected, 31 lesions (40.3%) were laterally spreading tumors, nongranular type. Nonpolypoid colorectal neoplasms (NP-CRNs), including flat (<10 mm), depressed, and laterally spreading, accounted for 59.7% of all detected ANs. Furthermore, 2 of the 4 CRCs corresponded to T1 NP-CRNs. CONCLUSIONS: Endoscopic removal of premalignant lesions, including NP-CRNs, effectively reduced CRC risk. More than half of metachronous ANs removed by surveillance colonoscopy were NP-CRNs. The Japan Polyp Study: University Hospital Medical Information Network Clinical Trial Registry: University Hospital Medical Information Network Clinical Trial Registry, C000000058; cohort study: UMIN000040731.

Potential for expanding indications and curability criteria of endoscopic resection for early gastric cancer in elderly patients: results from a Japanese multicenter prospective cohort study.

BACKGROUND AND AIMS: Evidence for endoscopic resection (ER) in elderly patients with early gastric cancer (EGC) is limited. We assessed its clinical outcomes, and explored new indications and curability criteria. METHODS: We analyzed data from a Japanese multicenter prospective cohort study. Patients aged ≥75 years with EGC treated with ER were included. We classified "eCuraC-2 (corresponding to noncurative ER, defined in the Japanese gastric cancer treatment guidelines)" into "elderly-high (EL-H)" (>10% estimated metastatic risk) and "elderly-low (EL-L)" (≤10%). RESULTS: In total, 3,371 patients with 3,821 EGCs were included; endoscopic submucosal dissection (ESD) was the prominent treatment choice. Among them, 3,586 lesions met the guidelines' ER indications and 235 did not. The proportions of en bloc and R0 resections and perforations were 98.9%, 94.4%, and 0.8%, respectively, in EGCs within the indications. In EGCs beyond the indications, they were 99.5%, 85.4%, and 5.9%, respectively, for lesions diagnosed as ≤3 cm, and 96.0%, 64.0%, and 18.0% for those >3 cm. Curative ER ("eCuraA/B") and EL-L were observed in 83.6% and 6.2% of lesions within the indications, respectively, and in 44.2% and 16.8% of lesions <3 cm beyond the indications, respectively. The 5-year cumulative gastric cancer death rates following eCuraA/B and EL-H were 0.3% (95% CI, 0.2-0.6) and 3.5% (2.0-5.7), respectively. Following EL-L, the rate was 0.9% (0.2-3.5) even without subsequent treatment. CONCLUSIONS: Usefulness of ESD for elderly EGC patients was confirmed by their clinical outcomes. Lesions ≤3 cm and EL-L emerged as new ER indication and curability criterion, respectively.

Endoscopic hand suturing using a modified through-the-scope needle holder for mucosal closure after colorectal endoscopic submucosal dissection: Prospective multicenter study (with video).

OBJECTIVES: Endoscopic hand suturing (EHS) is a novel technique for closing a mucosal defect after endoscopic submucosal dissection (ESD). We investigated the technical feasibility of colorectal EHS using a modified flexible through-the-scope needle holder. METHODS: This was a prospective multicenter study conducted at two referral centers between June 2022 and April 2023. This study included colorectal neoplasms 20-50 mm in size located in the sigmoid colon or rectum. A modified flexible through-the-scope needle holder, with an increased jaw width to facilitate needle grasping, was used for colorectal EHS. The primary end-points were sustained closure rate on second-look endoscopy (SLE) performed on postoperative days 3-4 and suturing time for colorectal EHS. Secondary end-points included complete closure rate and delayed adverse events. RESULTS: We enrolled 20 colorectal neoplasms in 20 patients, including four patients receiving antithrombotic agents. The tumor location was as follows: lower rectum (n = 8), upper rectum (n = 2), rectosigmoid colon (n = 4), and sigmoid colon (n = 6), and the median mucosal defect size was 37 mm (range, 21-65 mm). The complete closure rate was 90% (18/20 [95% confidence interval (CI) 68.3-98.8%]), and the median suturing time was 49 min (range, 23-92 min [95% CI 35-68 min]). Sustained closure rate on SLE was 85% (17/20 [95% CI 62.1-96.8%]). No delayed adverse events were observed. CONCLUSION: EHS demonstrated a high sustained closure rate. Given the long suturing time and technical difficulty, EHS should be reserved for cases with a high risk of delayed adverse events.

Endoscopist-related factors affecting adenoma detection during colonoscopy: Data from the J-SCOUT study.

OBJECTIVES: Colonoscopy withdrawal times are associated with the adenoma detection rate (ADR). However, the relationship between ADR and cecal insertion time has been inadequately characterized. We aimed to evaluate endoscopist-related factors involved in the ADR, including the average individual colonoscopy insertion and withdrawal times. METHODS: This observational study used a colonoscopy database with pathology data from routine clinical practice in Japanese institutions. The odds ratios (OR) of endoscopist-related factors related to ADRs were examined using a generalized linear mixed model. RESULTS: Of the 186,293 colonoscopies performed during the study period, 47,705 colonoscopies by 189 endoscopists in four hospitals were analyzed for ADR. The overall ADR was 38.3% (95% confidence interval [CI] 37.8, 38.7). Compared to endoscopists with mean cecal insertion times of <5 min, the OR of ADR for those with mean cecal insertion times of 5-9, 10-14, and ≥15 min were 0.84 (95% CI 0.71, 0.99), 0.68 (95% CI 0.52, 0.90), and 0.45 (95% CI 0.25, 0.78), respectively. Compared to endoscopists with mean withdrawal times of <6 min, the OR of ADR for those with mean withdrawal times of 6-9, 10-14, and ≥15 min were 1.38 (95% CI 1.03, 1.85), 1.48 (95% CI 1.09, 2.02), and 1.68 (95% CI 1.04, 2.61), respectively. There were no significant differences in ADRs by endoscopist specialty, gender, or the total number of examinations performed. CONCLUSION: Individual mean colonoscopy insertion time was associated with ADR and might be considered as a colonoscopy quality indicator as well as withdrawal time.

Proportions and characteristics of interval cancer in annual fecal immunochemical test screening and postcolonoscopy colorectal cancer: Results from a Japanese multicenter prospective study using questionnaires, the C-DETECT study.

OBJECTIVES: There are several types of colorectal cancer (CRC) according to the detection methods and intervals, including interval CRC (iCRC) and postcolonoscopy CRC (PCCRC). We aimed to examine their proportions and characteristics. METHODS: We conducted a multicenter prospective study using questionnaires in Japan ("C-DETECT study"), in which differences in CRC characteristics according to detection methods and intervals were examined from consecutive adult patients. Because the annual fecal immunochemical test (FIT) was used in population-based screening, the annual FIT-iCRC was assessed. RESULTS: In total, 1241 CRC patients (1064 with invasive CRC) were included. Annual FIT-iCRC (a), 3-year PCCRC (b), and CRC detected within 1 year after a positive FIT with noncompliance to colonoscopy (c) accounted for 4.5%, 7.0%, and 3.9% of all CRCs, respectively, and for 3.9%, 5.4%, and 4.3% of invasive CRCs, respectively. The comparison among these (a, b, c) and other CRCs (d) demonstrated differences in the proportions of ≥T2 invasion ([a] 58.9%, [b] 44.8%, [c] 87.5%, [d] 73.0%), metastasis ([a] 33.9%, [b] 21.8%, [c] 54.2%, [d] 43.9%), right-sided CRC ([a] 42.9%, [b] 40.2%, [c] 18.8%, [d] 28.6%), and female sex ([a] 53.6%, [b] 49.4%, [c] 27.1%, [d] 41.6%). In metastatic CRC, (a) and (b) showed a higher proportions of BRAF mutations ([a] [b] 12.0%, [c] [d] 3.1%). CONCLUSIONS: Annual FIT-iCRC and 3-year PCCRC existed in nonnegligible proportions. They were characterized by higher proportions of right-sided tumors, female sex, and BRAF mutations. These findings suggest that annual FIT-iCRC and 3-year PCCRC may have biological features different from those of other CRCs.

Factors associated with increased duration of endoscopic submucosal dissection for rectal tumors: a 22-year retrospective analysis.

BACKGROUND AND AIMS: Colorectal endoscopic submucosal dissection (ESD) is widely used in several countries. However, it is associated with technical difficulties. Rectal ESD is considered an intermediate step in colorectal ESD training. Nevertheless, some rectal lesions require a longer procedure time than usual, and the reason for the prolonged time taken for these specific lesions remains unclear. Therefore, this study aimed to clarify the factors associated with prolonged rectal ESD. METHODS: In total, 483 rectal lesions resected using ESD from February 1998 to June 2021 were investigated. Prolonged ESD procedure time was defined as the time from the first submucosal injection to lesion removal exceeding 120 minutes, whereas other procedures were defined as average ESD procedure time. Clinicopathologic and endoscopic findings were compared between the 2 groups using univariate and multivariate analyses. RESULTS: One hundred forty-four lesions were resected using a prolonged ESD procedure time of 202.9 ± 92.3 minutes, whereas 339 lesions were resected using an average ESD procedure time of 77.8 ± 29.4 minutes. Multivariate analysis revealed that tumors involving the dentate line (P = .026), resection size ≥50 mm (P < .001), invasion depth ≥T1b (P = .006), and circumferential range ≥2/3 (P = .001) were independent risk factors for prolonged-duration ESDs, regardless of whether the procedure was performed by an expert or not. CONCLUSIONS: The results of the present study suggest that the location of a lesion involving the dentate line, resection size ≥50 mm, circumferential range ≥2/3, and invasion depth ≥T1b are the independent risk factors for prolonged ESD procedure time.

Cost-effectiveness analysis of computer-aided detection systems for colonoscopy in Japan.

OBJECTIVES: The usefulness of computer-aided detection systems (CADe) for colonoscopy has been increasingly reported. In many countries, however, data on the cost-effectiveness of their use are lacking; consequently, CADe for colonoscopy has not been covered by health insurance. We aimed to evaluate the cost-effectiveness of colonoscopy using CADe in Japan. METHODS: We conducted a simulation model analysis using Japanese data to examine the cost-effectiveness of colonoscopy with and without CADe for a population aged 40-74 years who received colorectal cancer (CRC) screening with a fecal immunochemical test (FIT). The rates of receiving FIT screening and colonoscopy following a positive FIT were set as 40% and 70%, respectively. The sensitivities of FIT for advanced adenomas and CRC Dukes' A-D were 26.5% and 52.8-78.3%, respectively. CADe colonoscopy was judged to be cost-effective when its incremental cost-effectiveness ratio (ICER) was below JPY 5,000,000 per quality-adjusted life-years (QALYs) gained. RESULTS: Compared to conventional colonoscopy, CADe colonoscopy showed a higher QALY (20.4098 vs. 20.4088) and lower CRC incidence (2373 vs. 2415 per 100,000) and mortality (561 vs. 569 per 100,000). When the CADe cost was set at JPY 1000-6000, the ICER per QALY gained for CADe colonoscopy was lower than JPY 5,000,000 (JPY 796,328-4,971,274). The CADe cost threshold at which the ICER for CADe colonoscopy exceeded JPY 5,000,000 was JPY 6040. CONCLUSIONS: Computer-aided detection systems for colonoscopy has the potential to be cost-effective when the CADe cost is up to JPY 6000. These results suggest that the insurance reimbursement of CADe for colonoscopy is reasonable.

"Endoscopic" adenoma detection rate as a quality indicator of colonoscopy: First report from the J-SCOUT study.

OBJECTIVES: To examine whether reasonable detection rate of endoscopically diagnosed lesions as adenoma ("endoscopic" adenoma detection rate [ADR]) could be calculated with a database generated from colonoscopy reports and whether it could be used as a surrogate colonoscopy quality indicator of "pathological" ADR. METHODS: A lesion-by-lesion database of colonoscopies performed between 2010 and 2020 at eight Japanese endoscopy centers and corresponding pathology database were integrated. Differences in numbers of detected polyps, "endoscopic" and "pathological" adenomas, and what these differences could be attributed to were examined. Polyp detection rate (PDR), "endoscopic" and "pathological" ADRs, and correlation coefficients between "pathological" ADR and PDR or "endoscopic" ADR by each endoscopist were calculated. RESULTS: Overall, 129,065 colonoscopy reports were analyzed. Among a total of 146,854 polyps, more "endoscopic" adenomas (n = 117,359) were observed than "pathological" adenomas (n = 70,076), primarily because adenomas were not resected on site, rather than because of a misdiagnosis. In all patients analyzed, PDR, "endoscopic" and "pathological" ADRs were 56.4% (95% confidence interval [CI] 56.2-56.7), 48.0% (95% CI 47.7-48.3), and 32.7% (95% CI 32.5-33.0), respectively. "Endoscopic" and "pathological" ADRs from each endoscopist showed a high correlation in hospitals where adenomas were usually resected at the time of examination. CONCLUSIONS: By appropriately describing endoscopically diagnosed lesions as "adenomas" in endoscopy reports, "endoscopic" ADR might be used as a surrogate colonoscopy quality indicator of "pathological" ADR (UMIN000040690).

Short-term outcomes of endoscopic resection for colorectal neuroendocrine tumors: Japanese multicenter prospective C-NET STUDY.

OBJECTIVES: The incidence of colorectal neuroendocrine tumors (NETs) has increased with colorectal cancer screening programs and increased colonoscopies. The management of colorectal NETs has recently shifted from radical surgery to endoscopic resection. We aimed to evaluate the short-term outcomes of various methods of endoscopic resection for colorectal NETs. METHODS: Among those registered in the C-NET STUDY, patients with colorectal NETs who underwent endoscopic treatment as the initial therapy were included. Short-term outcomes, such as the en bloc resection rate and R0 resection (en bloc resection with tumor-free margin) rate, were analyzed based on treatment modalities. RESULTS: A total of 472 patients with 477 colorectal NETs received endoscopic treatment. Of these, 418 patients with 421 lesions who met the eligibility criteria were included in the analysis. The median age of the patients was 55 years, and 56.9% of them were men. The lower rectum was the most commonly affected site (88.6%), and lesions <10 mm accounted for 87% of the cases. Endoscopic submucosal resection with a ligation device (ESMR-L, 56.5%) was the most common method, followed by endoscopic submucosal dissection (ESD, 31.4%) and endoscopic mucosal resection using a cap (EMR-C, 8.5%). R0 resection rates <10 mm were 95.5%, 94.8%, and 94.3% for ESMR-L, ESD, and EMR-C, respectively. All 16 (3.8%) patients who developed treatment-related complications could be treated conservatively. Overall, 23 (5.5%) patients had incomplete resection without independent clinicopathological risk factors. CONCLUSION: ESMR-L, ESD, and EMR-C were equally effective and safe for colorectal NETs with a diameter <10 mm.

Third Asia-Pacific consensus recommendations on colorectal cancer screening and postpolypectomy surveillance.

The Asia-Pacific region has the largest number of cases of colorectal cancer (CRC) and one of the highest levels of mortality due to this condition in the world. Since the publishing of two consensus recommendations in 2008 and 2015, significant advancements have been made in our knowledge of epidemiology, pathology and the natural history of the adenoma-carcinoma progression. Based on the most updated epidemiological and clinical studies in this region, considering literature from international studies, and adopting the modified Delphi process, the Asia-Pacific Working Group on Colorectal Cancer Screening has updated and revised their recommendations on (1) screening methods and preferred strategies; (2) age for starting and terminating screening for CRC; (3) screening for individuals with a family history of CRC or advanced adenoma; (4) surveillance for those with adenomas; (5) screening and surveillance for sessile serrated lesions and (6) quality assurance of screening programmes. Thirteen countries/regions in the Asia-Pacific region were represented in this exercise. International advisors from North America and Europe were invited to participate.

Two vs One Forward View Examination of Right Colon on Adenoma Detection: An International Multicenter Randomized Trial.

BACKGROUND & AIMS: Second forward view (SFV) examination of the right colon (RC) in colonoscopy was suggested to improve the adenoma detection rate (ADR), but multicenter data to inform its routine use remain limited. We performed an international multicenter randomized trial comparing SFV vs a standard single forward view examination of the RC on adenoma detection. METHODS: Asymptomatic individuals undergoing screening or surveillance colonoscopies from 6 Asia Pacific regions were invited for study. A forward view examination of the RC was first performed in all patients, followed by randomization at the hepatic flexure to either SFV examination of the RC and standard withdrawal examination from the hepatic flexure to rectum, or a standard withdrawal colonoscopy (SWC) examination from the hepatic flexure to rectum. The primary outcome was RC ADR. RESULTS: Between 2016 and 2019, there were 1011 patients randomized (SFV group, 502 patients; SWC group, 509 patients). Forty-five endoscopists performed the colonoscopies. The RC ADR was significantly higher in the SFV group than in the SWC group (27.1% vs 21.6%; P = .042). The whole-colon ADR was high in both groups (49.0% vs 45.0%; P =.201). The SFV examination identified 58 additional adenomas in 49 patients (9.8%), leading to a change in surveillance recommendations in 15 patients (3.0%). The median overall withdrawal time was 1.5 minutes longer in the SFV group (12.0 vs 10.5 min; P < .001). Older age, male sex, ever smoking, and longer RC withdrawal time were independent predictors of right-sided adenoma detection. CONCLUSIONS: In this multicenter trial, SFV examination significantly increased the RC ADR in screening and surveillance colonoscopies. Routine RC SFV examination should be considered. ClinicalTrials.gov ID: NCT03121495.

Comparison of postpolypectomy bleeding events between cold snare polypectomy and hot snare polypectomy for small colorectal lesions: a large-scale propensity score-matched analysis.

BACKGROUND AND AIMS: Cold snare polypectomy (CSP), a safe procedure for removing colon polyps, has a low prevalence of postpolypectomy bleeding (PPB). Previous studies have failed to demonstrate differences in PPB rates between CSP and hot snare polypectomy (HSP), possibly because of their small sample sizes. This study analyzed PPB rates after CSP and HSP. METHODS: This was a retrospective analysis of colorectal lesions (diameter <10 mm) treated using endoscopic resection at our institution between January 2015 and December 2019. Resections were performed using CSP or HSP, depending on the endoscopist's preference. Endoscopic and histologic findings were recorded in the endoscopic database at our institution. Propensity score (PS) matching was performed to match patient age, lesion size, macroscopic features, location of the lesions, clipping after resection, and antithrombotic agent use. The CSP and HSP groups were compared to determine the adverse event (PPB) rates. RESULTS: The CSP and HSP groups included 12,928 and 2408 lesions (total of 5371 patients), respectively. Univariate analysis revealed that the overall prevalence of PPB after HSP was higher than that after CSP (odds ratio [OR], 5.39; 95% confidence interval [CI], 2.50-11.60). After PS matching (2135 lesions per group), the prevalence of PPB after HSP remained higher than that after CSP (OR, 6.0; 95% CI, 1.34-26.8). CONCLUSIONS: For colorectal lesions <10 mm in diameter, the risk of PPB after CSP is significantly lower than that after HSP, after PS matching. CSP for lesions <10 mm could be safely performed compared with HSP.

New scoring system to distinguish deep invasive submucosal and muscularis propria colorectal cancer during colonoscopy: a development and global multicenter external validation study (e-T2 Score).

BACKGROUND AND AIMS: Diagnostics to differentiate deep submucosal invasive (invasion depth ≥1000 µm [T1b]) colorectal cancer (CRC) from muscularis propria invasive (T2) CRC are limited. We aimed to establish and validate a scoring system that differentiates T1b from T2. METHODS: A multicenter retrospective cross-validation study was performed. Four hundred sixty-one consecutive pathologically confirmed T1b or T2 CRCs were divided into the development (T1b, 222; T2, 189) and internal validation (T1b, 31; T2, 19) cohorts. Eight potential endoscopic findings were evaluated using the development cohort: loss of lobulation, deep depression, demarcated depressed area, protuberance within the depression, expanding appearance, fold convergency, erosion or white plaque, and Borrmann type 2 or 3 tumor. A scoring system that differentiates T1b from T2 was developed, and diagnostic performance was tested using the internal validation cohort by 8 endoscopists. External validation was conducted using 50 CRC images by 4 endoscopists from other institutions, including outside of Japan. RESULTS: Multivariate analysis identified the following 5 independent predictive endoscopic findings of T2 CRC: deep depression (odds ratio [OR], 2.08; 95% confidence interval [CI], 1.07-4.04), demarcated depressed area (OR, 4.40; 95% CI, 1.39-13.9), 4-fold convergency or more (OR, 3.41; 95% CI, 1.90-6.11), erosion or white plaque (OR, 8.28; 95% CI, 2.77-24.7), and Borrmann type 2 or 3 tumor (OR, 8.76; 95% CI, 3.58-21.5). The area under the receiver-operating characteristic curve (AUROC) was .90 (95% CI, .87-.93) in the development cohort, .80 (95% CI, .76-.85) in the internal validation, and .76 (95% CI, .69-.83) in the external validation. CONCLUSIONS: We established and validated a new scoring system to differentiate T1b from T2 CRC using 5 simple endoscopic findings.

Detection rates of colorectal neoplasia during colonoscopies and their associated factors in the SCREESCO study.

BACKGROUND AND AIM: Colonoscopy quality, including lesion detectability, is variable, and factors influencing lesion detection are not fully understood. This study investigated lesion detection rates during colonoscopies and the associated factors in the SCREEning of Swedish COlons (SCREESCO) study. METHODS: In this cross-sectional analysis of data from SCREESCO, a large-scale randomized controlled trial of colorectal cancer screening in the Swedish population aged 60 years, we assessed data of first-time colonoscopies performed in both colonoscopy and fecal immunochemical test (FIT) arms. RESULTS: This study included 16 552 individuals. The adenoma detection rate was 23.9% and 37.8% in colonoscopy and FIT arms, respectively. Regarding colonoscopy procedures, a withdrawal time ≥ 6 min was associated with higher detection rates of advanced adenomas (adjusted odds ratio [AOR] 2.474, 95% confidence interval [CI] 1.295-4.723), adenomas (2.181, 1.515-3.140), and proximal serrated lesions (pSLs) (1.713, 1.007-2.915). Antispasmodic use was associated with higher detection rates of these lesions and sessile serrated lesions (SSLs) (AOR, 95% CI: 1.523, 1.295-1.791; 1.361, 1.217-1.522; 1.450, 1.247-1.687; and 1.810, 1.512-2.167, respectively). Insertion time > 20 min was related to lower detection rates of adenomas, pSLs, and SSLs (AOR, 95% CI: 0.753, 0.639-0.887; 0.640, 0.495-0.828; and 0.704, 0.518-0.955, respectively). The relationship between a recent period and higher detection rates of pSLs and SSLs was also demonstrated. CONCLUSION: Lesion detectability in SCREESCO was mostly acceptable with room for improvement. In addition to sufficient withdrawal time, antispasmodic use and acquiring skills enabling short insertion time may improve lesion detection. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02078804.

Management of elderly patients with early gastric cancer in Japan.

Management of elderly patients with early gastric cancer is an important issue in an aging society such as Japan. While endoscopic resection is recommended as the standard treatment for early gastric cancers with extremely low risk of lymph node metastasis (<1%), gastrectomy with lymphadenectomy is recommended for the other early gastric cancers as the standard treatment even in elderly patients. Endoscopic submucosal dissection is the most recommended endoscopic resection procedure because of its high ability for 'en bloc' resection. Endoscopic submucosal dissection can reportedly provide favorable short-term outcomes in elderly patients. In terms of patient prognosis, the importance of considering patients' physical and nutritional conditions before endoscopic submucosal dissection has recently attracted attention. With respect to gastrectomy, the nationwide data in Japan have demonstrated relatively low 5-year overall survival and non-negligible post-operative 90-day mortality in men aged ≥75 years and women aged ≥80 years compared with those in younger patients. Among these elderly patients, 20% or more reportedly died within 5 years after gastrectomy mostly due to other diseases. These facts suggested the necessity of a less invasive management option for the elderly patients. Efforts are being made to provide a non-invasive follow-up option without gastrectomy following endoscopic resection in elderly patients. To avoid the increase in gastric cancer-related deaths, the selection of patients with relatively low lymph node metastasis risk is essential, and several tools to estimate the lymph node metastasis risk from early gastric cancers have been developed. To avoid overtreatment with gastrectomy in more elderly early gastric cancer patients, new endoscopic submucosal dissection indications for them are also warranted.

Epidemiological Trends and Future Perspectives of Gastric Cancer in Eastern Asia.

BACKGROUND: The global epidemiological situation of gastric cancer has changed considerably over time, and it is essential to understand the epidemiological trends and future perspectives of gastric cancer. SUMMARY: Although gastric cancer was common in the United States less than a century previously, it is no longer common in this country. Currently, over 60% of gastric cancers are found in Eastern Asia. In some Eastern Asian countries such as Japan and Korea, population-based gastric cancer screening has been conducted using upper gastrointestinal endoscopy or radiography to lower gastric cancer mortality. Due to earlier detection of gastric cancer, the survival of patients with gastric cancer is more favorable in these countries than in other Western countries. Even in Eastern Asia, a remarkable decrease in the age-standardized incidence and mortality of gastric cancer has been observed. This downward trend is mainly due to the reduced Helicobacter pylori infection, and this trend is considered to continue. Nevertheless, both the absolute number of incident cases and deaths of gastric cancer are still increasing at present due to the aging population. For the time being, the management of gastric cancer in elderly population is a critical issue in Eastern Asia. The absolute numbers of gastric cancer cases and deaths are believed to peak in the near future, following the decreasing age-standardized incidence and mortality. Key Messages: After a long period, gastric cancer may become a rare cancer even in Eastern Asia, and new efficient approaches for its prevention, screening, and treatment are warranted.

Conditional inference tree models to perceive depth of invasion in T1 colorectal cancer.

BACKGROUND AND AIM: Accurate diagnosis of invasion depth for T1 colorectal cancer is of critical importance as it decides optimal resection technique. Few reports have previously covered the effects of endoscopic morphology on depth assessment. We developed and validated a novel diagnostic algorithm that accurately predicts the depth of early colorectal cancer. METHODS: We examined large pathological and endoscopic databases compiled between Jan 2015 and Dec 2018. Training and validation data cohorts were derived and real-world diagnostic performance of two conditional interference tree algorithms (Models 1 and 2) was evaluated against that of the Japan NBI-Expert Team (JNET) classification used by both expert and non-expert endoscopists. RESULTS: Model 1 had higher sensitivity in deep submucosal invasion than that of JNET alone in both training (45.1% vs. 28.6%, p < 0.01) and validation sets (52.3% vs. 40.0%, p < 0.01). Model 2 demonstrated higher sensitivity than Model 1 (66.2% vs. 52.3%, p < 0.01) in excluding deeper invasion of suspected Tis/T1a lesions. CONCLUSION: We discovered that machine-learning classifiers, including JNET and macroscopic features, provide the best non-invasive screen to exclude deeper invasion for suspected Tis/T1 lesions. Adding this algorithm improves depth diagnosis of T1 colorectal lesions for both expert and non-expert endoscopists.

Diagnostic efficacy of the Japan NBI Expert Team classification with dual-focus magnification for colorectal tumors.

BACKGROUND AND AIMS: The Japan NBI Expert Team (JNET) classification is the first unified classification criteria for colorectal tumors using magnifying narrow-band imaging (NBI) in Japan. However, the diagnostic stratification ability of the JNET classification with dual-focus magnifying NBI (DF-JNET) has remained obscure. The aim of this study was to validate the diagnostic stratification ability of DF-JNET for colorectal tumors in two Japanese referral centers. METHODS: A multicenter retrospective image evaluation study was conducted by three experienced endoscopists, including an original JNET member who was also involved in establishing the diagnostic criteria. A total of two images, namely, one representative non-magnified white light image and one representative DF-NBI image for each of the 557 consecutive lesions were used in the evaluation study. The diagnostic value of DF-JNET was calculated based on the evaluation data. RESULTS: The sensitivity, specificity, positive and negative predictive values, and accuracy of DF-JNET Type 1 for differentiating between non-neoplastic and neoplastic lesions were 78.1%, 98.6%, 89.1%, 96.8%, and 95.9%, respectively; of Type 2A lesions for differentiating low-grade dysplasia from others were 98.0%, 76.5%, 94.9%, 89.7%, and 94.1%, respectively; of Type 2B lesions for differentiating high-grade dysplasia and shallow submucosal invasive carcinoma from others were 43.5%, 99.1%, 66.7%, 97.6%, and 96.8%, respectively; and of Type 3 lesions for differentiating deep submucosal invasive carcinoma from others were 83.3%, 99.5%, 62.5%, 99.8%, and 99.3%, respectively. CONCLUSIONS: All DF-JNET types had an over 90% diagnostic accuracy for the histological prediction of colorectal tumors. DF-JNET might contribute to appropriate treatment choices, such as endoscopic resection or surgery, not only in Japan but also in Western countries in which the use of optical zoom endoscopy is limited.

Endoscopic features of isolated and traditional serrated adenoma-associated superficially serrated adenomas of the colorectum.

BACKGROUND AND AIM: Superficially serrated adenoma (SuSA) is a recently proposed subtype of colorectal serrated lesions. It is characterized by distinct clinicopathological and molecular features, including mixed serrated and adenomatous histology and frequent genetic alterations involving KRAS and RSPO. This study aimed to characterize the endoscopic features of isolated and traditional serrated adenoma (TSA)-associated SuSAs. METHODS: We retrospectively evaluated the endoscopic findings of 25 isolated SuSAs and 21 TSA-associated SuSAs that were histologically and molecularly characterized. RESULTS: SuSAs appeared as a sessile polyp or slightly elevated lesion located mostly in the sigmoid colon and rectum (88%). The size was between 3 and 20 mm (median, 6 mm). Most of them exhibited KRAS mutations (96%) and RSPO fusions/overexpression (92%). Endoscopically, many lesions had a whitish color (84%), a distinct border (96%), an irregular border (76%), and a lobulated surface (72%). However, diminutive lesions exhibited overlapping features with hyperplastic polyps. On narrow-band imaging, vessel patterns were invisible or appeared as lacy microvessels in most lesions (80%). Chromoendoscopy invariably showed stellar or elongated/branched stellar pits, indicating a serrated microarchitecture. Most TSA-associated SuSAs typically presented as polyps with a two-tier raised appearance, consisting of whitish lower and reddish higher components corresponding to a SuSA and a TSA, respectively. CONCLUSIONS: SuSAs exhibit several characteristic endoscopic features on white-light and image-enhanced endoscopy. Diminutive lesions exhibit endoscopic features overlapping with hyperplastic polyps. Nonetheless, the endoscopic diagnosis of larger and TSA-associated SuSAs may be feasible.

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.