Predictors of technical difficulty for trainees in esophageal endoscopic submucosal dissection.

BACKGROUND: Esophageal endoscopic submucosal dissection (ESD) is technically challenging, especially for trainees, and requires a safe training system. This study aimed to identify predictors of technical difficulty facing trainees performing esophageal ESD to establish such system. METHODS: This was a single-center retrospective study of patients with esophageal cancer who underwent ESD performed by trainees between January 2010 and August 2022. Technical difficulties were defined as muscularis propria exposure and long procedure time (≥ 90 min). Factors associated with these technical difficulties were investigated. RESULTS: A total of 798 lesions in 721 patients were evaluated. Muscularis propria exposure occurred in 298 lesions (37.3%), including 10 perforations (1.3%). The procedure time was ≥ 90 min in 134 lesions (16.8%). In the multivariate analysis, tumor size ≥ 20 mm, tumors ≥ 1/2 of the circumference, and those close to previous treatment scars significantly increased the incidence of both difficulties, whereas tumors in the upper esophagus significantly decreased this incidence. Furthermore, female sex and tumors in the left wall were independent predictors of muscularis propria exposure, and elevated morphology was an independent predictor of long procedure time. Muscularis propria exposure and long procedure time occurred in more than half of the cases with three or more predictors of each difficulty. CONCLUSIONS: Large tumors and tumors close to previous treatment scars increase technical difficulties for trainees in esophageal ESD. Conversely, tumors in the upper esophagus reduce these difficulties. These results enable us to predict the difficulty level preoperatively and select appropriate cases in stepwise training.

Multiple foci of dilated vessels as a new predictor of metachronous esophageal cancer.

OBJECTIVES: Prediction of the risk of esophageal squamous cell carcinoma (SCC) by endoscopic findings without iodine staining, which is irritating to the esophagus, would be beneficial. In a previous retrospective study, we found that multiple foci of dilated vascular areas (MDV) of the esophageal mucosa, seen in narrow-band imaging (NBI)/blue laser imaging (BLI), are associated with iodine-unstained lesions and, thus, may be a predictor of esophageal SCC. This prospective study aimed to investigate the association between MDV and metachronous esophageal SCC. METHODS: Patients with a history of endoscopic resection for esophageal SCC were included in the study. First, evaluation of the MDV using NBI or BLI was conducted during the initial endoscopy. The patients were then monitored for metachronous esophageal SCC by endoscopic surveillance. The association between the number of MDV and incidence of metachronous esophageal SCC was investigated. RESULTS: From February 2018 to May 2019, 206 patients were enrolled and 201 patients were included in the analysis. Patients were followed up until October 2022. The median (interquartile range) endoscopic follow-up period was 1260 (1105-1348) days. The incidence of metachronous esophageal SCC at 2 years was 7.1% in patients with MDV ≤4 and 13.9% in patients with MDV ≥5 (P < 0.01). In the multivariate analysis, MDV was an independent predictor of metachronous esophageal SCC, with an odds ratio (95% confidence interval) of 2.37 (1.06-5.31). CONCLUSION: Multiple foci of dilated vascular area is a useful predictor for stratifying the risk of metachronous esophageal SCC.

Potential role of a novel endoscopic retrieval bag for large colorectal resected specimen: a proof-of-concept study.

Endoscopic submucosal dissection enables en bloc resection of large superficial colorectal neoplasms. However, it is sometimes challenging to retrieve a large resected specimen via the anus without sample fragmentation. A novel "bag-type" retrieval device has been developed to accomplish complete isolation and non-destructive delivery of oversized specimens. This single-center retrospective study was performed to demonstrate the efficacy of this device for large colorectal resected specimens. Among 17 patients, we identified 18 superficial colorectal lesions for which the use of a novel retrieval device (Endo Carry Large Type) was indicated at specimen delivery at a referral cancer institute from March 2021 to July 2022. The median (interquartile range) tumor size was 62.5 (52.0-79.5) mm. Retrieval of 17 (94%) of 18 resected specimens was performed using the Endo Carry Large Type, and 16 (89%) were successfully retrieved without sample fragmentation. The median (interquartile range) retrieval time was 4 (4-8) minutes, and no apparent adverse events were observed. The novel Endo Carry Large Type device can accomplish colorectal specimen retrieval safely and quickly without specimen damage and therefore may contribute to accurate pathological diagnosis.

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.

Endoscopic resection for local residual or recurrent cancer after definitive chemoradiotherapy or radiotherapy for esophageal squamous cell carcinoma.

Chemoradiotherapy (CRT) and radiotherapy (RT) are treatment options for esophageal squamous cell carcinoma (ESCC), but local residual/recurrent cancer after CRT/RT is a major problem. Endoscopic resection (ER) is an effective treatment option for local residual/recurrent cancer. To ensure the efficacy of ER, complete removal of endoscopically visible lesions with cancer-free vertical margins is desired. This study aimed to identify the endoscopic parameters associated with the complete endoscopic removal of local residual/recurrent cancer. In this single-center, retrospective study, we used a prospectively maintained database to identify esophageal lesions that were diagnosed as local residual/recurrent cancer after CRT/RT and treated by ER between January 2012 and December 2019. We evaluated the associations of endoscopic R0 resection with findings on conventional endoscopy and endoscopic ultrasonography (EUS). In total, 98 lesions (83 cases) were identified from our database. The rate of endoscopic R0 resection was higher for flat lesions (100% versus 77%, P = 0.00014). EUS was performed for 24 non-flat lesions, and endoscopic R0 resection was achieved for 94% of lesions with an uninterrupted fifth layer. Flat lesions on conventional endoscopy and lesions with an uninterrupted fifth layer on EUS are good candidates for ER.

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.

A single-center prospective study evaluating the usefulness of artificial intelligence for the diagnosis of esophageal squamous cell carcinoma in a real-time setting.

BACKGROUND: Several pre-clinical studies have reported the usefulness of artificial intelligence (AI) systems in the diagnosis of esophageal squamous cell carcinoma (ESCC). We conducted this study to evaluate the usefulness of an AI system for real-time diagnosis of ESCC in a clinical setting. METHODS: This study followed a single-center prospective single-arm non-inferiority design. Patients at high risk for ESCC were recruited and real-time diagnosis by the AI system was compared with that of endoscopists for lesions suspected to be ESCC. The primary outcomes were the diagnostic accuracy of the AI system and endoscopists. The secondary outcomes were sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and adverse events. RESULTS: A total of 237 lesions were evaluated. The accuracy, sensitivity, and specificity of the AI system were 80.6%, 68.2%, and 83.4%, respectively. The accuracy, sensitivity, and specificity of endoscopists were 85.7%, 61.4%, and 91.2%, respectively. The difference between the accuracy of the AI system and that of the endoscopists was - 5.1%, and the lower limit of the 90% confidence interval was less than the non-inferiority margin. CONCLUSIONS: The non-inferiority of the AI system in comparison with endoscopists in the real-time diagnosis of ESCC in a clinical setting was not proven. TRIAL REGISTRATION: Japan Registry of Clinical Trials (jRCTs052200015, 18/05/2020).

Predictors of stricture after non-circumferential endoscopic submucosal dissection of the esophagus and single-dose triamcinolone injection immediately after the procedure.

BACKGROUND AND AIMS: Local triamcinolone (TA) injection is widely used to prevent stricture formation after endoscopic submucosal dissection (ESD). However, stricture develops in up to 45% of patients despite this prophylactic measure. We therefore conducted a single-center prospective study to identify predictors of stricture after esophageal ESD and local TA injection. METHODS: Patients who underwent esophageal ESD and local TA injection and who were comprehensively assessed for lesion- and ESD-related factors were included in the study. Multivariate analyses were conducted to identify the predictors of stricture. RESULTS: A total of 203 patients were included in the analysis. Multivariate analysis identified residual mucosal width ≤5 mm (odds ratio [OR], 29.0; P < .0001) or 6 to 10 mm (OR, 3.7; P = .04), history of chemoradiotherapy (OR, 5.1; P = .045), and tumor in the cervical or upper thoracic esophagus (OR, 3.8; P = .018) as independent predictors of stricture. Based on the ORs of the predictors, patients were stratified into 2 groups according to stricture risk: patients in the high-risk group (residual mucosal width ≤5 mm or 6-10 mm with another predictor) had a stricture rate of 52.5% (31 of 59 cases), and patients in the low-risk group (residual mucosal width ≥11 mm or 6-10 mm without other predictors) had a stricture rate of 6.3% (9 of 144 cases). CONCLUSIONS: We identified predictors of stricture after ESD and local TA injection. Local TA injection prevented stricture formation after ESD in low-risk patients but was not sufficient to prevent stricture in high-risk patients. Additional interventions should thus be considered in high-risk patients. (University Hospital Medical Network Clinical Trials Registry number: UMIN 000028894.).

Boring biopsy with rapid on-site evaluation for gastric gastrointestinal stromal tumor: A pilot study.

One of 4 patients (25%) and 2 of 3 patients (67%) were correctly diagnosed by conventional and hot boring biopsies, respectively. The median procedure time of conventional and hot boring biopsies was 21 (range, 13-33) and 17 (range, 16-23) min, respectively. Rapid on-site evaluation was performed totally 12 times in 7 patients. The positive and negative predictive values of rapid on-site evaluation for gastrointestinal stromal tumor were 0.5 (0.12-0.88) and 1.0 (0.42-1.00), respectively.

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.

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.

Clinical features of superficial esophagus squamous cell carcinoma according to alcohol-degrading enzyme ADH1B and ALDH2 genotypes.

BACKGROUND: Inactivated alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are related to esophageal carcinogenesis. We aimed to clarify the clinical features associated with the alcohol-degrading enzyme genotypes, ADH1B and ALDH2. We also investigated the risk factors for metachronous esophageal squamous cell carcinoma (ESCC) and head and neck SCC (HNSCC). METHODS: We conducted a single-center, retrospective study including patients with ESCC treated by endoscopic resection. Patients were recruited between October 2020 and September 2021. Buccal mucosal swabs were obtained from them to analyze the genetic polymorphisms affecting ADH (ADH1B) and ALDH (ALDH2) activity. Patients were categorized into three groups: both inactivated = double-inactivated group; inactivated ADH1B or ALDH2 = single-inactivated group; and both activated = activated group. RESULTS: Among the 297 enrolled patients, patients in the double-inactivated group were significantly younger (P < 0.001) and 60% of them were ≤ 50 years old. This group also had more ESCCs located in the upper esophagus (P < 0.001) and more simultaneous multiple ESCCs (P = 0.044). More than half of the patients had multiple Lugol-voiding lesions (LVLs) (P < 0.001) and heavy alcohol consumers (P = 0.012). Metachronous ESCC and HNSCC were more common in the double-inactivated group (P < 0.001, P = 0.001). Multivariate analysis identified located in the upper esophagus, multiple LVLs and history of HNSCC as risk factors for metachronous ESCC. CONCLUSIONS: Activation patterns of alcohol-metabolizing enzymes were related to age at ESCC onset, lesion location, and metachronous ESCC and HNSCC. Different approaches to the prophylaxis and treatment of esophageal cancer should be considered, depending on the enzyme activity pattern.

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.

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.

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.

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.