A machine learning model for predicting the lymph node metastasis of early gastric cancer not meeting the endoscopic curability criteria.

BACKGROUND: We developed a machine learning (ML) model to predict the risk of lymph node metastasis (LNM) in patients with early gastric cancer (EGC) who did not meet the existing Japanese endoscopic curability criteria and compared its performance with that of the most common clinical risk scoring system, the eCura system. METHODS: We used data from 4,042 consecutive patients with EGC from 21 institutions who underwent endoscopic submucosal dissection (ESD) and/or surgery between 2010 and 2021. All resected EGCs were histologically confirmed not to satisfy the current Japanese endoscopic curability criteria. Of all patients, 3,506 constituted the training cohort to develop the neural network-based ML model, and 536 constituted the validation cohort. The performance of our ML model, as measured by the area under the receiver operating characteristic curve (AUC), was compared with that of the eCura system in the validation cohort. RESULTS: LNM rates were 14% (503/3,506) and 7% (39/536) in the training and validation cohorts, respectively. The ML model identified patients with LNM with an AUC of 0.83 (95% confidence interval, 0.76-0.89) in the validation cohort, while the eCura system identified patients with LNM with an AUC of 0.77 (95% confidence interval, 0.70-0.85) (P = 0.006, DeLong's test). CONCLUSIONS: Our ML model performed better than the eCura system for predicting LNM risk in patients with EGC who did not meet the existing Japanese endoscopic curability criteria. We developed a neural network-based machine learning model that predicts the risk of lymph node metastasis in patients with early gastric cancer who did not meet the endoscopic curability criteria.

Efficacy and safety of intensive downstaging polypectomy (IDP) for multiple duodenal adenomas in patients with familial adenomatous polyposis: a prospective cohort study.

BACKGROUND: Patients with familial adenomatous polyposis (FAP) risk developing multiple duodenal adenomas (MDAs), leading to duodenal cancer and death. We investigated the efficacy and safety of intensive downstaging polypectomy (IDP) for MDAs integrated with new-generation procedures. METHODS: This prospective phase II study, conducted at a tertiary cancer center, enrolled patients with FAP who had MDAs. We performed IDP including cold snare/forceps polypectomy (CSP/CFP) and underwater endoscopic mucosal resection (UEMR). The primary end point was the downstaging of Spigelman stage at 1-year follow-up. RESULTS: 2424 duodenal polyps in 58 patients with FAP underwent IDP, including 2413 CSPs in 57 patients, seven CFPs in one patient, and four UEMRs in four patients. Only one major adverse event was observed (grade 3 hyperamylasemia) without clinical manifestations. We performed additional UEMR, CSP, and CFP for one, 12, and 22 patients, respectively, during initial follow-up. Overall, 55 patients completed protocol examination; the Spigelman stage was significantly reduced at the 1-year follow-up endoscopy (P < 0.001), with downstaging observed in 39 patients (71 %). Among the 26 patients with Spigelman stage IV at initial examination and protocol completion, 23 (88 %) showed downstaging. There was no major change in Spigelman stages from 1-year follow-up esophagogastroduodenoscopy to a median of 37 months (range 3-56). CONCLUSIONS: IDP, including new-generation procedures, showed significant downstaging with acceptable adverse events for MDA in patients with FAP, even those with advanced-stage disease. Lesion selection for different resection techniques may be important for suitable and sustainable management of MDA in patients with FAP.

Endoscopic features of gastric neuroendocrine carcinoma.

BACKGROUND AND AIM: The endoscopic features of gastric neuroendocrine carcinoma (G-NEC) have not been clarified; therefore, they were investigated in relation to clinicopathological findings. METHODS: Consecutive patients with G-NECs who had undergone endoscopic or surgical resection at our institution between January 2005 and March 2022 were included in this retrospective study. The endoscopic and clinicopathological findings of the lesions were analyzed to provide information of diagnostic value. In addition, cases of gastric neuroendocrine tumor (G-NET) and common-type gastric adenocarcinoma treated in the same study period were identified to compare the endoscopic findings between each G-NEC versus G-NET, and G-NEC versus common-type gastric adenocarcinoma. Patients with common-type gastric adenocarcinoma were matched for age, sex, tumor size, and depth of tumor invasion in 1:3 ratio. RESULTS: Among 15 patients with 15 G-NECs, submucosal tumor-like marginal elevation (87%), adherent white coat (67%), and ulceration with a distinct border (60%) were characteristic endoscopic findings in white-light images. Magnifying narrow-band imaging endoscopy revealed an absent microsurface (MS) pattern plus disrupted irregular microvessel (MV) in five (71%) of seven cases with evaluable MS and MV patterns. The area with an absent MS pattern plus disrupted irregular MV corresponded to the histological finding of NEC component in all five cases. These endoscopic features were all significantly more frequent in G-NECs than G-NETs (n = 22) or common-type gastric adenocarcinomas (n = 45). CONCLUSIONS: These endoscopic features should be taken into consideration to increase the index of suspicion and to improve the accuracy of target biopsies for G-NEC.

Feasibility of underwater endoscopic mucosal resection for endoscopic management of gastric neoplasms in patients with familial adenomatous polyposis.

BACKGROUND: Underwater endoscopic mucosal resection (UEMR) has been developed as an effective endoscopic intervention for colon, rectum, and duodenum neoplasms. However, there are no comprehensive reports regarding the stomach, and its safety and efficacy are unknown. We aimed to examine the feasibility of UEMR for gastric neoplasms in patients with familial adenomatous polyposis (FAP). METHODS: We retrospectively extracted data of patients with FAP who underwent endoscopic resection (ER) for gastric neoplasms at Osaka International Cancer Institute from February 2009 to December 2018. Elevated gastric neoplasms of ≤ 20 mm in diameter were extracted, and conventional endoscopic mucosal resection (CEMR) and UEMR were compared. Furthermore, outcomes after ER until March 2020 were examined. RESULTS: 91 endoscopically resected gastric neoplasms were extracted from 31 patients with 26 pedigrees, and 12 neoplasms underwent CEMR and 25 neoplasms underwent UEMR was compared. The procedure time was shorter for UEMR than for CEMR. There was no significant difference between en bloc resection and R0 resection rates by EMR methods. CEMR and UEMR showed postoperative hemorrhage rates of 8% and 0%, respectively. Residual/local recurrent neoplasms were identified in four lesions (4%), but additional endoscopic intervention (three UEMR and one cauterization) resulted in a local cure. CONCLUSION: UEMR was feasible in gastric neoplasms of FAP patients, especially in elevated lesions and those of ≤ 20 mm in diameter.

Long-term outcomes after endoscopic resection for late-elderly patients with early gastric cancer.

BACKGROUND AND AIMS: With the population aging, the incidence of early gastric cancer (EGC) is increasing. We aimed to clarify the indications for endoscopic resection (ER) in late-elderly patients with EGC in terms of life expectancy. METHODS: Patients aged ≥75 years who underwent ER for EGC at our institution from January 2007 to December 2012 were enrolled. Clinical data, including Eastern Cooperative Oncology Group performance status (ECOG-PS), Charlson comorbidity index, and Prognostic Nutritional Index (PNI), were collected at the time of ER. Overall survival (OS) was the main outcome measure. RESULTS: Four hundred consecutive patients were enrolled. Mean patient age was 79.3 years (range, 75-93). The 5-year follow-up rate was 89.0% (median follow-up period, 5.6 years). Five-year OS was 80.8% (95% confidence interval [CI], 76.4-84.4), and 5-year net survival standardized for age, sex, and calendar year was 1.09 (95% CI, 1.03-1.15). With a multivariate analysis, ECOG-PS 2 to 4 (hazard ratio, 8.84; 95% CI, 3.07-25.4), PNI <49.1 (hazard ratio, 2.49; 95% CI, 1.53-4.06), and eCura C-2 (hazard ratio, 1.79; 95% CI, 1.11-2.88) were independent prognostic factors. When none of these factors was met, the 5-year OS rate was 90.4% (95% CI, 84.0-94.3). CONCLUSIONS: ER for EGC in late-elderly patients may improve life expectancy. ER is recommended in patients with a good ECOG-PS and PNI and in whom ER is expected to be non-eCura C-2.

Indication of emergency colonoscopy after colorectal endoscopic submucosal dissection: A proposal of hematochezia scale.

BACKGROUND AND AIM: Hematochezia is a major adverse event associated with colorectal endoscopic submucosal dissection (ESD). This study aimed to distinguish between hematochezia that required endoscopic hemostasis and hematochezia that required no hemostasis. METHODS: This retrospective study included consecutive patients who underwent ESD for colorectal tumors at the Osaka International Cancer Institute between September 2017 and August 2020. The exclusion criteria were as follows: patients with coexisting advanced colorectal cancers or inflammatory bowel diseases, patients who received incomplete ESD or emergency surgery, or patients who underwent ESD for multiple lesions. We evaluated whether the patients had hematochezia and underwent emergency colonoscopy and hemostasis during hospitalization. The degree of hematochezia in the saved photographs was assessed using the hematochezia scale and classified as mild, moderate, or severe. Blood pressure, heart rate, time from ESD to first hematochezia, and total number of hematochezia episodes were also evaluated. RESULTS: Among the 437 patients who underwent ESD, 44 were excluded, and 393 patients were evaluated. Hematochezia was observed in 100 patients (25%). Emergency colonoscopy was performed in 12 patients (3%), and hemostasis was required in six patients (2%). For patients with hematochezia, only mild hematochezia and hematochezia that developed ≤ 48 h after ESD were significantly associated with no intervention for hemostasis. The positive predictive value for no intervention for hemostasis was 100% (93-100%) for mild hematochezia and 98% (93-100%) for hematochezia ≤ 48 h. CONCLUSIONS: Mild hematochezia and hematochezia ≤ 48 h were negative predictors of hemostasis, in which emergency colonoscopy may be avoided.

Impact of endoscopic surveillance on mortality of metachronous esophageal and head and neck cancer after esophageal endoscopic resection.

BACKGROUND AND AIM: As more superficial esophageal cancer (EC) patients are being treated with endoscopic resection (ER), it is important to understand the outcomes, including survival data, of patients who develop metachronous EC and head and neck cancer (HNC). We aimed to evaluate the long-term surveillance and survival outcomes of metachronous EC and HNC after esophageal ER. METHODS: This study included 627 patients who underwent ER of superficial esophageal squamous cell carcinoma from 2008 to 2016 and were generally followed by annual or biannual esophagogastroduodenoscopy up to 2019 at Osaka International Cancer Institute. Data on metachronous cancer development and causes of death were collected from an integrated database of hospital-based cancer registry and Vital Statistics of Japan. RESULTS: During a median (range) follow-up period of 67.4 (3.8-142.7) months, 230 patients (36.7%) developed 500 metachronous ECs and 126 patients (20.1%) developed 239 metachronous HNCs, post-ER of index EC. The 3-year, 5-year, and 7-year cumulative incidences were 25.8%, 36.0%, and 43.6% for metachronous EC and 10.9%, 16.0%, and 26.9% for metachronous HNC, respectively. No patients died of metachronous EC, and only seven patients (1.1%) died of metachronous HNC. The 3-year, 5-year, and 7-year disease-specific survival rates were 99.8%, 99.6%, and 98.6%, respectively. CONCLUSIONS: The incidences of metachronous EC and HNC increase with time over 5 years after esophageal ER; therefore, surveillance endoscopy should be continued over 5 years. Endoscopic surveillance is useful for survivors after esophageal ER given the high incidence and extremely low mortality of metachronous EC and HNC.

Positive predictive value of the clinical diagnosis of T1a-epithelial/lamina propria esophageal cancer depends on lesion size.

OBJECTIVES: Endoscopic resection (ER) is a minimally invasive treatment for esophageal squamous cell carcinoma (ESCC). However, stricture may develop after ER for widespread lesions. Application of ER is justified if these cancers are pathological T1a-epithelial/lamina propria (pEP/LPM) cancers that can be cured by ER. We conducted a study to clarify the association between pathological invasion depth and lesion size or circumference in clinical (c) EP/LPM cancers. METHODS: From our database, we identified patients diagnosed with cEP/LPM ESCC via endoscopic examination who underwent endoscopic or surgical tumor resection. The accuracy of the cEP/LPM ESCC diagnosis was determined by histologically diagnosing cancer invasion depth as a reference standard. RESULTS: Between January 2015 and December 2019, 1271 cancer patients were diagnosed with cEP/LPM ESCC, of which 1195 (94.0%) were correctly diagnosed with pEP/LPM cancer. The positive predictive value (PPV) classified according to lesion sizes of ≤25, 26-49, and ≥50 mm was 95.8% (981/1024 lesions), 89.7% (191/213 lesions), and 67.6% (23/34 lesions), respectively. PPV according to the circumferential extent of <3/4, ≥3/4, and <1, and whole was 94.6% (1164/1230 lesions), 75.0% (24/32 lesions), and 77.8% (7/9 lesions), respectively. In multivariate analysis, the PPV of cEP/LPM ESCC was significantly associated with lesion size (P < 0.001) and male sex. CONCLUSIONS: Between January 2015 and December 2019, 1271 cancer patients were diagnosed with cEP/LPM ESCC, of which 1195 (94.0%) were correctly diagnosed with pEP/LPM cancer. The PPV of cEP/LPM ESCC was related to lesion size. Treatment should be determined considering the high risk of cancer invasion into the muscularis mucosa or deeper in cEP/LPM cancers with a lesion size of ≥50 mm.

Endoscopic Features of Superficial Esophageal Squamous Cell Carcinoma in Patients with Very Low Risk Factors (Female, Nondrinking, and Nonsmoking): A Case-Control Study.

BACKGROUND: Although esophageal squamous cell carcinoma (ESCC) is more likely to develop in patients with any risk factor (male, drinking, or smoking), it is sometimes detected in patients with very low risk factors (female, nondrinking, and nonsmoking). We examined the endoscopic features of superficial ESCC in patients with very low risk factors. METHODS: In this single-center case-control study, 666 patients with 666 superficial ESCC lesions were divided into 2 groups: those with very low risk factors (very low-risk group, n = 34) and those with any risk factors (any-risk group, n = 632). After case-control selection at a 1:5 ratio, the very low-risk group comprised 34 patients and the any-risk group comprised 170 patients. We compared the baseline characteristics, endoscopic findings, and treatment results (including pathological diagnosis) between the 2 groups. RESULTS: There were no statistically significant differences between the 2 groups in age, tumor size, tumor location, tumor morphology, or treatment results (including tumor depth and lymphovascular invasion). A longitudinal lesion with an attachment of white keratinized epithelium was more likely to be detected in the very low-risk group than the any-risk group (61.8 vs. 17.6%, respectively; p < 0.001). CONCLUSIONS: ESCC in patients with very low risk factors is rare but can be encountered in daily practice. A longitudinal lesion with an attachment of white keratinized epithelium is its main characteristic, which is slightly different from that of patients with any risk factors.

Features of Esophageal Adenocarcinoma in Magnifying Narrow-Band Imaging.

BACKGROUND: Several endoscopic classifications for esophageal adenocarcinoma have been proposed; however, gastric adenocarcinoma is much more common than esophageal or esophagogastric junctional (EGJ) adenocarcinoma in East Asian countries. We, therefore, investigated whether an endoscopic diagnostic algorithm for gastric adenocarcinoma could be used for esophageal or EGJ adenocarcinoma. METHODS: One hundred eighteen consecutive patients who underwent endoscopic resection or surgery for intramucosal esophageal or EGJ adenocarcinoma, at the Osaka International Cancer Institute between January 2006 and December 2017, were included in this retrospective study. Their lesions were classified as Siewert type 1 or 2, and the presence of endoscopic magnifying narrow-band imaging findings for diagnosing gastric adenocarcinoma was evaluated. RESULTS: We evaluated 125 adenocarcinomas in 118 patients (29 type 1 and 96 type 2). Demarcation lines (DLs) were seen in 7 (24%) type 1 and 53 (55%) type 2 lesions. Irregular mucosal patterns were present in 2 (7%) type 1 and 22 (23%) type 2 lesions. Irregular vascular patterns were present in 26 (90%) type 1 and 50 (52%) type 2 lesions. According to the magnifying endoscopy diagnostic algorithm for gastric adenocarcinoma, only 7 (24%) type 1 and 52 (54%) type 2 lesions were correctly diagnosed as cancers (p = 0.005). CONCLUSION: The magnifying endoscopy diagnostic algorithm for gastric cancer may not be useful for esophageal or EGJ adenocarcinomas because of the low visibility of DLs, especially in Siewert type 1 adenocarcinoma.

Underwater endoscopic mucosal resection versus endoscopic submucosal dissection for 20-30 mm colorectal polyps.

BACKGROUND AND AIM: Endoscopic submucosal dissection (ESD) for large polyps provides a high en bloc resection rate, accurate pathological diagnosis, and low recurrence rate. However, ESD requires advanced techniques, and underwater endoscopic mucosal resection (UEMR) is an alternative. We investigated the efficacy and safety of UEMR for 20-30 mm colorectal lesions compared with ESD. METHODS: We retrospectively evaluated systematically collected data of patients who underwent UEMR or ESD for 20-30 mm sessile colorectal lesions. Outcome measures were the incidence of local recurrence, procedure time, en bloc resection rate, and incidence of adverse events. We performed propensity score matching and inverse probability weighting adjustment to control for possible confounders. RESULTS: We evaluated 125 patients undergoing UEMR and 306 patients undergoing ESD. Using propensity score matching, we analyzed 74 lesions in each group. UEMR had a shorter procedure time than ESD [6.7 min (95% confidence interval (CI), 5.3-8.1 min) vs 64.8 min (95% CI, 57.4-72.2 min), respectively]. Although the en bloc resection rate with UEMR was inferior to ESD [61% (95% CI, 49-72%) vs 99% (95% CI, 93-100%), respectively], there was no significant difference in the local recurrence rate between the procedures [0% (95% CI, 0-4.0%) in each group]. Inverse probability weighting adjustment revealed that neither ESD nor UEMR had a significant association with local recurrence. CONCLUSIONS: Underwater endoscopic mucosal resection for 20-30  mm colorectal lesions was comparable with ESD regarding long-term outcomes, with a shorter procedure time, despite the lower en bloc resection rate.

Pre-ampullary location and size ≥10 mm are independent predictors for high-grade superficial non-ampullary duodenal epithelial tumors.

BACKGROUND AND AIM: The incidence of identified superficial non-ampullary duodenal epithelial tumors (SNADETs) has been increasing with recent advances in endoscopic diagnosis. Nevertheless, the clinical features of SNADETs with malignant potential remain unclear. The aim of the present study was to clarify the clinical characteristics of high-grade SNADETs. METHODS: A total of 328 SNADETs that had been endoscopically or surgically resected between January 2013 and April 2019 were identified from an endoscopic and pathological database. Clinical characteristics were compared between mucosal low-grade neoplasm (n = 154) and mucosal high-grade neoplasm/submucosal carcinoma (HGN/SMC, n = 174). RESULTS: In univariate analysis, tumor size, pre-ampullary tumor location, red color, and rough/nodular surface were significantly associated with HGN/SMC. In multivariate analysis (odds ratio [95% confidence interval]), large (≥10 mm) tumor size (odds ratio: 4.5, 95% confidence interval: 2.6-7.7, P < 0.001) and pre-ampullary tumor location (odds ratio: 2.1, 95% confidence interval: 1.3-3.5, P = 0.004) were independent predictors for HGN/SMC. Analysis of histological phenotypes revealed that the proportion of tumors that were HGN/SMC was much greater for gastric-type tumors (21/23 lesions, 91%) than for intestinal-type tumors (150/302 lesions, 50%) (P < 0.001) and that all gastric-type tumors were located in the pre-ampullary portion. CONCLUSIONS: Pre-ampullary location and large tumor size are independent predictors for HGN/SMC SNADETs. Pre-ampullary tumor location is significantly associated with gastric histological phenotype. These findings may help in decision making for endoscopic treatment, active indication for pre-ampullary tumor or tumor ≥10 mm, and understanding the pathophysiology of SNADETs.

Propensity score-matched analysis of endoscopic resection for recurrent colorectal neoplasms: A pilot study.

BACKGROUND AND AIM: Local residual/recurrent colorectal lesions after endoscopic resection (ER) are difficult to treat with conventional ER. Underwater endoscopic mucosal resection (UEMR) and endoscopic submucosal dissection (ESD) are reportedly effective. We investigated the appropriate indications of ESD and UEMR for recurrent colorectal lesions. METHODS: This single-center, retrospective, observational study was conducted at a tertiary cancer institute. Patients who underwent UEMR or ESD for residual/recurrent colorectal lesions after ER from October 2013 to February 2019 were enrolled. Propensity score matching was performed between the UEMR and ESD groups to compare the clinical characteristics, treatment, and outcomes. RESULTS: In total, 30 UEMRs and 21 ESDs were performed. Median (range) diameter of the lesions was 8 mm (2-22 mm) in UEMR and 15 mm (2-58 mm) in ESD. Median procedure time in UEMR was significantly shorter than that of ESD (4 min [2-15 min] vs 70 min [17-193 min], P < 0.001). En bloc and complete resection rates of ESD were significantly higher than that of UEMR (73% vs 100%, 41% vs 81%, respectively). No adverse events occurred with UEMR, but there were two cases (10%) of delayed perforation with ESD. Neither group reported recurrence after treatment. Propensity score-matched cases showed significantly shorter procedure time and hospitalization period in UEMR than in ESD. CONCLUSIONS: The outcomes of UEMR and ESD were comparable. UEMR could be a useful salvage therapy for small local residual/recurrent colorectal lesions after ER with shorter procedure time and hospitalization period.

Favorable long-term outcomes of endoscopic resection for nonampullary duodenal neuroendocrine tumor.

BACKGROUND AND AIM: The long-term outcomes of endoscopic resection for nonampullary duodenal neuroendocrine tumors are limited. We aimed to clarify it. METHODS: Consecutive patients with nonampullary duodenal neuroendocrine tumors endoscopically treated at our institute between January 2005 and June 2020 were included in this retrospective study. En bloc and R0 resection rates and adverse events were evaluated as short-term outcomes of endoscopic resection. The 5-year overall and recurrence-free survival rates of patients after endoscopic resection were calculated as long-term outcomes. RESULTS: Of 34 patients with 34 lesions, 33 patients (97%) underwent endoscopic mucosal resection, and one (3%) underwent endoscopic submucosal dissection. En bloc resection was achieved in 33 lesions (97%). R0 resection was achieved in 20 lesions (59%). The median tumor size was 6 mm (range: 3-13). Thirty-one lesions (91%) and three lesions (9%) were classified as G1 and G2, respectively. Lymphovascular invasion was observed in six lesions (18%). Intraprocedural perforation occurred in four patients (12%) who were conservatively treated with endoscopic closure. All 34 patients were followed up without additional treatment after endoscopic resection, and no recurrence or metastasis developed during the median follow-up period of 47.9 months (range: 9.0-187.1). The 5-year overall survival and recurrence-free survival rates were 87.1% and 100%, respectively. CONCLUSIONS: Endoscopic resection provided a favorable long-term prognosis for patients with nonampullary duodenal neuroendocrine tumors without lymph node metastasis.

Endoscopic findings in the soft palatal mucosa are associated with the risk of esophageal squamous cell carcinoma.

BACKGROUND AND AIM: We investigated endoscopic findings of the soft palatal mucosa to identify factors associated with esophageal squamous cell carcinoma (ESCC). METHODS: This study was conducted during endoscopic examinations of subjects at Osaka International Cancer Institute from January 2020 through May 2020. We took endoscopic images of the soft palate under non-magnifying and mild-magnifying observations. Subjects with ESCC or a history of ESCC were defined as the ESCC group. Two endoscopists who were blinded to subjects' clinical information interpreted 10 endoscopic findings: melanosis, brownish changes, whitish epithelium, vasodilation, circular alignment of dilated vessels, uneven surface, uneven epithelial color, uneven vessel visibility, palate ridge, and erosion. Subjects were interviewed about their alcohol use, smoking, and flushing reactions. RESULTS: Two hundred eighty-two subjects, including 151 in the ESCC group and 131 in the non-ESCC group, were included in the analysis. Univariate analyses and multivariate logistic regression demonstrated that melanosis, whitish epithelium, and vasodilation were significantly associated with ESCC. The positive likelihood ratios (PLRs) of melanosis, whitish epithelium, and vasodilation were 3.3, 4.2, and 2.8, respectively. Additionally, the PLRs for three of the endoscopic findings in subjects with drinking and smoking habits were higher than in those without these habits-PLRs ranging from 7.23 to 19.1. High PLRs for three endoscopic findings suggested a high possibility of ESCC. Interobserver agreement was substantial for whitish epithelium, moderate for melanosis, and fair for vasodilation. CONCLUSIONS: Three endoscopic findings in soft palate were considered to be useful as alarming signs that indicate ESCC risk.

Magnifying endoscopy with crystal violet staining for immune checkpoint inhibitor-associated colitis.

BACKGROUND AND AIM: There exists no evidence on the relationship between endoscopic and histologic findings. Furthermore, even after multiple biopsy specimens were obtained, histologic examination usually fails to show the characteristic features of immune checkpoint inhibitor-associated colitis. In this study, we explored the endoscopic and histologic findings of immune checkpoint inhibitor-associated colitis. METHODS: Patients diagnosed with immune checkpoint inhibitor-associated colitis at our hospital between March 2018 and December 2018 were retrospectively assessed. The degree of mucosal inflammation was evaluated using endoscopic inflammation grade (inactive, mild, moderate, or severe disease) and further observed using magnifying endoscopy with crystal violet staining. Pit structures were classified into three types: regularly arranged pits with circular or elliptical shape (R type), irregularly arranged pits with inhomogeneous size and morphology (IR type), and pits with reduced density or pits that partially disappeared (AD type). RESULTS: Eleven patients (median age, 71 years; range, 44-83 years) were diagnosed with immune checkpoint inhibitor-associated colitis. All characteristic histologic findings, including crypt distortion, crypt abscesses, and apoptotic bodies, were observed at sites with moderate-to-severe endoscopic inflammation but not at sites with inactive-to-mild endoscopic inflammation. Characteristic histologic features were observed in 0%, 50%, and 100% of R-type, IR-type, and AD-type mucosa, respectively. CONCLUSIONS: We revealed the possible utility of endoscopic images for selecting suitable target sites for biopsy and showed that endoscopic findings could reduce the time lag associated with tissue diagnosis and sampling errors due to biopsy.

Curative value of underwater endoscopic mucosal resection for submucosally invasive colorectal cancer.

BACKGROUND AND AIM: Occasionally, colorectal tumors without characteristics of deep submucosal invasion are found to be invasive upon pathological evaluation after endoscopic resection (ER). Because the resection depth for underwater endoscopic mucosal resection (UEMR) has not been clarified, we evaluated the feasibility of UEMR for pathologically invasive colorectal cancer (pT1-CRC). METHODS: We retrospectively investigated data on the backgrounds and outcomes of patients with pT1-CRC who underwent UEMR between January 2014 and June 2019 at our institute. As a reference standard, the backgrounds and outcomes of pT1-CRCs that had undergone conventional EMR (CEMR) were also investigated. RESULTS: Thirty-one patients (median age, 68 years [range, 32-88 years]; 22 men [71%]) were treated with UEMR. Median lesion size was 17 mm (range, 6-50 mm). The endoscopic complete resection rate was 100%. The overall en bloc resection rate was 77%, and the VM0, HM0, and R0 resection rates were 81%, 58%, and 55%, respectively. In cases of pT1a (invasion <1000 µm)-CRC (n = 14), the en bloc, VM0, and R0 resection rates were 92%, 100%, and 71%, respectively. Seventeen patients (five with risk factors for lymph node metastasis and 12 without) were followed up, and no local recurrence and distant metastasis were observed during the follow-up period (median follow-up period, 18 months [range, 6-62 months]) after UEMR. The outcomes of UEMR seemed to be comparable with those of CEMR (n = 32). CONCLUSIONS: The VM0 rate of UEMR for pT1-CRC, especially for pT1a-CRC, without characteristics of deep submucosal invasion seems feasible.

Long-term outcomes after endoscopic submucosal dissection for differentiated-type early gastric cancer that fulfilled expanded indication criteria: A prospective cohort study.

BACKGROUND AND AIM: Endoscopic resection for early gastric cancer (EGC) is widely performed. However, there is still a paucity of strong evidence regarding long-term outcomes after endoscopic submucosal dissection (ESD) for the expanded indication criteria of the Japanese guidelines (ver. 2010). METHODS: Endoscopic submucosal dissection was performed in patients with EGC that met the expanded indication criteria: (i) cT1a, differentiated-type EGC of 2 to 5 cm, ulcer negative or (ii) cT1a, differentiated-type EGC of ≤3 cm, ulcer positive. Patients whose pathological examination fulfilled the curative resection criteria were then enrolled in this cohort study: negative vertical margin, negative lymphovascular invasion, and (i) pT1a, differentiated-type, and ulcer negative; (ii) pT1a, differentiated-type, ≤3 cm, and ulcer positive; or (iii) pT1b1 (<500-µm submucosal invasion), differentiated-type, and ≤3 cm. Patients with only a positive horizontal margin as a noncurative factor were included for follow-up. RESULTS: From September 2003 to February 2012, a total of 356 patients underwent ESD, and 214 were enrolled in the survival analysis. One hundred twenty patients (56%) had >2 cm in diameter and ulcer-negative lesions, and 94 (44%) had ≤3 cm and ulcer-positive lesions. The vital status at 5 years after ESD was confirmed in all (100%) patients. No local or metastatic recurrence was detected; however, 26 metachronous gastric cancers developed, and 1 patient died of metachronous gastric cancer. The 5-year disease-specific and overall survival rates were 99.5% (95% confidence interval [CI], 97.2%-100%) and 93.9% (95% CI, 89.8%-96.4%), respectively. CONCLUSION: ESD for EGC that fulfills the expanded criteria is feasible and shows favorable long-term outcomes.

Validity of endoscopic resection for clinically diagnosed T1a-MM/T1b-SM1 N0 M0 esophageal squamous cell carcinoma.

BACKGROUND: Previous guidelines have not described clear recommendations for performing endoscopic resection (ER) of T1a-muscularis mucosa (MM)/T1b-submucosal (SM1) cancers that have invaded ≤ 200 µm because these are considered to have a non-negligible risk of metastasis based on previous analyses of pathologically diagnosed (p)MM/SM1 cancers. Considering that the indication for ER is determined based on a clinical diagnosis, the applicability of ER should be investigated in clinical (c)MM/SM1 but not pMM/SM1 cancers. This study aimed to evaluate validity of ER for cMM/SM1 cancers. METHODS: In total, 175 cMM/SM1 esophageal squamous cell carcinoma cases that were endoscopically or surgically resected between January 2008 and December 2018 were identified from a prospectively maintained database. We histologically evaluated resected specimens and divided them into low- (n = 92) and high-risk (n = 83) cancers for metastasis. RESULTS: Univariate analysis showed that longer tumor length and larger circumferential extent were significantly correlated with high-risk cancer (P < 0.001). Multivariate analysis showed that tumor circumference was an independent predictor of high-risk cancer (P = 0.036). The proportion of low-risk cancers among cases with ≤ 3/4, > 3/4 and < 1, and whole circumferential extent were 59, 17, and 14%, respectively, and the post-ER stricture rates of these groups were 12, 33, and 100%, respectively. CONCLUSION: ER is the first-line treatment for cMM/SM1 cancers with ≤ 3/4 circumferential extent considering that 59% of cMM/SM1 cancers were low-risk cancers for which ER is mostly curative. ER is not recommended for whole circumferential cMM/SM1 cancers given the low proportion of low-risk cancers and the high risk of stricture after ER.

Delineating the extent of esophageal squamous cell carcinoma.

BACKGROUND: Lugol chromoendoscopy has been conventionally used for the detection and delineation of esophageal squamous cell carcinoma (SCC). However, the boundaries of some lesions are unclear even with Lugol chromoendoscopy, and there is a risk of residual lesions or over-excision. This study aimed to evaluate the utility of narrow-band imaging (NBI) for the delineation of esophageal SCC in endoscopic resection. METHODS: Among 367 esophageal SCCs endoscopically resected between January and December 2019 at our institute, this retrospective study included consecutive lesions, which were first marked with NBI, followed by Lugol chromoendoscopy. The proportion of residual cancer, which was defined as histologically proven cancer confirmed adjacent to the scar within 1 year after endoscopic resection, was evaluated. To evaluate whether the marks added by Lugol chromoendoscopy after NBI marking were more reliable, we evaluated the presence of cancer in the iodine-unstained area outside the NBI-determined marks, i.e., the cancerous area missed by NBI. The presence of cancer in the iodine-stained areas inside the NBI-determined marks, i.e., the cancerous area missed by Lugol, was also evaluated. These were compared to assess the risk of residual cancer in endoscopic resection with NBI and Lugol chromoendoscopy. RESULTS: Among 304 lesions, 2 (0.7%) residual cancers were detected. The cancerous area missed by NBI and the cancerous area missed by Lugol were identified in 18 (6%) and 43 (14%) lesions, respectively (P = 0.001). CONCLUSIONS: NBI might be acceptable for delineating the extent of esophageal SCCs that are difficult to delineate with Lugol chromoendoscopy.