Randomized controlled trial of artificial intelligence diagnostic system in clinical practice to detect esophageal squamous cell carcinoma.

Background Artificial intelligence (AI) has made remarkable progress in image recognition using deep learning systems and has been used to detect esophageal squamous cell carcinoma (ESCC). However, all previous reports were not investigated in clinical settings, but in a retrospective design. Therefore, we conducted this trial to determine how AI can help endoscopists detect ESCC in clinical settings. Methods This was a prospective, single-center, exploratory, and randomized controlled trial. High-risk patients with ESCC undergoing screening or surveillance esophagogastroduodenoscopy were enrolled and randomly assigned to either the AI or control group. In the AI group, the endoscopists watched both the AI monitor detecting ESCC with annotation and the normal monitor simultaneously, whereas in the control group, the endoscopists watched only the normal monitor. In both groups, the endoscopists observed the esophagus using white-light imaging (WLI), followed by narrow-band imaging (NBI) and iodine staining. The primary endpoint was the enhanced detection rate of ESCC by non-experts using AI. The detection rate was defined as the ratio of WLI/NBI-detected ESCCs to all ESCCs detected by iodine staining. Results A total of 320 patients were included in this analysis. The detection rate of ESCC in non-experts was 47% in the AI group and 45% in the control group (p=0.93), with no significant difference, was similar to that in experts (87% vs. 57%, p=0.20) and all endoscopists (57% vs. 50%, p=0.70). Conclusions This study could not demonstrate an improvement in the esophageal cancer detection rate using the AI diagnostic support system for ESCC.

Long- vs short-segment Barrett's esophagus-derived adenocarcinoma: clinical features and outcomes of endoscopic submucosal dissection.

BACKGROUND: The incidence of Barrett's esophageal adenocarcinoma (BEA) is increasing, and endoscopic submucosal dissection (ESD) has been frequently performed for its treatment. However, the differences between the characteristics and ESD outcomes between short- and long-segment BEA (SSBEA and LSBEA, respectively) are unclear. We compared the clinicopathological characteristics and short- and long-term outcomes of ESD between both groups. METHODS: We retrospectively reviewed 155 superficial BEAs (106 SSBEAs and 49 LSBEAs) treated with ESD in 139 patients and examined their clinicopathological features and ESD outcomes. SSBEA and LSBEA were classified based on whether the maximum length of the background mucosa of BEA was < 3 cm or ≥ 3 cm, respectively. RESULTS: Compared with SSBEA, LSBEA showed significantly higher proportions of cases with the macroscopically flat type (36.7% vs. 5.7%, p < 0.001), left wall location (38.8% vs. 11.3%, p < 0.001), over half of the tumor circumference (20.4% vs. 1.9%, p < 0.001), and synchronous lesions (17.6% vs. 0%, p < 0.001). Compared with SSBEA, regarding ESD outcomes, LSBEA showed significantly longer resection duration (91.0 min vs. 60.5 min, p < 0.001); a lower proportion of submucosal invasion (14.3% vs. 29.2%, p = 0.047), horizontal margin negativity (79.6% vs. 94.3%, p = 0.0089), and R0 resection (69.4% vs. 86.8%, p = 0.024); and a higher proportion of post-procedural stenosis cases (10.9% vs. 1.9%, p = 0.027). The 5-year cumulative incidence of metachronous cancer in patients without additional treatment was significantly higher for LSBEA than for SSBEA (25.0% vs. 0%, p < 0.001). CONCLUSIONS: The clinicopathological features of LSBEA and SSBEA and their treatment outcomes differed in many aspects. As LSBEAs are difficult to diagnose and treat and show a high risk of metachronous cancer development, careful ESD and follow-up or eradication of the remaining BE may be required.

Prognostic factors for patients 85 years or older undergoing endoscopic submucosal dissection for early gastric cancer.

BACKGROUND: Little is known about prognostic factors for patients 85 years or older undergoing endoscopic submucosal dissection for early gastric cancer. Therefore, this study aimed to identify such prognostic factors. METHODS: We retrospectively evaluated the long-term outcomes and prognostic factors of 143 patients 85 years or older undergoing endoscopic submucosal dissection for early gastric cancer at a single-center between October 2005 and September 2020. Using the Kaplan-Meier method and a Cox proportional hazards regression model, we examined the relationships of patient characteristics and endoscopic curability (additional gastrectomy recommended [eCuraC-2] or not recommended) with overall survival. RESULTS: The median age of the patients was 86 years, and most patients were men (65%). The eCuraC-2 rate was 14.7%. During the follow-up period, 55 patients died; however, only two patients died due to gastric cancer. The 3-year and 5-year overall survival rates were 91.5% and 74.7%, respectively. Male sex (hazard ratio, 2.23; 95% confidence interval, 1.16-4.30), American Society of Anesthesiologists Physical Status of 3 (hazard ratio, 2.57; 95% confidence interval, 1.32-4.99), body mass index < 18.9 kg/m2 (hazard ratio, 2.21; 95% confidence interval, 1.11-4.40), and eCuraC-2 (hazard ratio, 3.04; 95% confidence interval, 1.37-6.75) were identified as independent prognostic factors. Moreover, patients with eCuraC-2 had significantly more poor prognostic factors than those who did not. CONCLUSIONS: The decision to perform endoscopic submucosal dissection for patients with the aforementioned prognostic factors should be carefully considered because follow-up without endoscopic submucosal dissection is possible.

Rebound Acid Hypersecretion after Withdrawal of Long-Term Proton Pump Inhibitor (PPI) Treatment-Are PPIs Addictive?

Proton pump inhibitors (PPIs) are widely used in the long-term treatment of gastroesophageal reflux disease (GERD) and other upper gastrointestinal disorders, such as the healing of peptic ulcers and/or prophylactic treatment of peptic ulcers. PPIs are also widely used as symptomatic treatment in patients with functional dyspepsia. One of the adverse effects of the long-term use of PPI is rebound acid hypersecretion (RAHS), which can occur after the withdrawal of PPI therapy due to a compensatory increase in gastric acid production. Mechanisms of the RAHS have been well established. Studies have shown that pentagastrin-stimulated acid secretion after the discontinuation of PPIs increased significantly compared to that before treatment. In healthy volunteers treated with PPIs, the latter induced gastrointestinal symptoms in 40-50% of subjects after the discontinuation of PPI therapy but after stopping the placebo. It is important for practicing physicians to be aware and understand the underlying mechanisms and inform patients about potential RAHS before discontinuing PPIs in order to avoid continuing unnecessary PPI therapy. This is important because RAHS may lead patients to reuptake PPIs as symptoms are incorrectly thought to originate from the recurrence of underlying conditions, such as GERD. Mechanisms of RAHS have been well established; however, clinical implications and the risk factors for RAHS are not fully understood. Further research is needed to facilitate appropriate management of RAHS in the future.

Risk stratification for synchronous/metachronous recurrence after endoscopic submucosal dissection for Barrett's esophageal adenocarcinoma using the length of Barrett's esophagus.

BACKGROUND: In Japan, the standard management of Barrett's esophageal adenocarcinoma after endoscopic submucosal dissection involves follow-up; however, multifocal synchronous/metachronous lesions are sometimes observed after endoscopic submucosal dissection. Risk stratification of multifocal cancer facilitates appropriate treatment, including eradication of Barrett's esophagus in high-risk cases; however, no effective risk stratification methods have been established. Thus, we identified the risk factors for multifocal cancer and explored risk-stratified treatment strategies for residual Barrett's esophagus. METHODS: We retrospectively reviewed the data of 97 consecutive patients with superficial Barrett's esophageal adenocarcinomas who underwent curative resection with endoscopic submucosal dissection. Multifocal cancer was defined by the presence of synchronous/metachronous lesions during follow-up. We used Cox regression analysis to identify the risk factors for multifocal cancer and subsequently analyzed differences in cumulative incidences. RESULTS: The cumulative incidences of multifocal cancer at 1, 3, and 5 years were 4.4%, 8.6%, and 10.7%, respectively. Significant risk factors for multifocal cancer were increased circumferential and maximal lengths of Barrett's esophagus. The cumulative incidences of multifocal cancer at 3 years were lower for patients with circumferential length < 4 cm and maximal length < 5 cm (2.9% and 1.2%, respectively) than for patients with circumferential length ≥ 4 cm and maximal length ≥ 5 cm (51.5% and 49.1%, respectively). CONCLUSIONS: Risk stratification of multifocal cancer using length of Barrett's esophagus was effective. Further multicenter prospective studies are needed to substantiate our findings.

Effect of Helicobacter pylori eradication evaluated using magnifying endoscopy with narrow-band imaging in mixed-type early gastric Cancer.

BACKGROUND: The effect of Helicobacter pylori (H.pylori) eradication therapy on mixed-histological-type gastric cancer remains unclear. This study aimed to clarify the effect of H. pylori eradication therapy on mixed-histological-type early gastric cancer using endoscopic and histological findings. METHODS: This single-center, retrospective study included patients with mixed-histological-type gastric cancer who underwent endoscopic submucosal dissection at the Cancer Institute Hospital. We compared detailed magnifying endoscopy with narrow-band imaging findings between eradicated and non-eradicated groups of patients with differentiated-type- and undifferentiated-type-predominant cancers. Subsequently, we performed histological evaluations of the non-cancerous epithelium covering differentiated-type components. RESULTS: A total of 124 patients with mixed-type early gastric cancer were enrolled (eradicated group: 62 differentiated-type-predominant cancer patients and 8 undifferentiated-type-predominant cancer patients; non-eradication group: 40 differentiated-type-predominant cancer patients and 14 undifferentiated-type-predominant cancer patients). Regarding differentiated-type-predominant cancer, differentiated-type findings were detected in all patients in eradicated and non-eradicated groups. The difference in the detection rate of undifferentiated-type findings between both groups was not significant in differentiated-type-predominant cancer patients. In differentiated-type-predominant cancers, the percentage of non-cancerous epithelium covering differentiated-type components was higher in the eradicated group than in the non-eradicated group (median: 60% vs. 40%, p < 0.001). CONCLUSIONS: Although the pathological findings of differentiated-type-predominant cancer were affected by H. pylori eradication, eradication did not affect the diagnosis of differentiated-type-predominant early gastric cancer using magnifying endoscopy with narrow-band imaging. ME-NBI is useful for the early detection of D-MIX EGCs and diagnosis of histological types during endoscopy, regardless of whether H. pylori eradication therapy has been administered.

Genomic features of Helicobacter pylori-naïve diffuse-type gastric cancer.

Helicobacter pylori (HP) is a major etiologic driver of diffuse-type gastric cancer (DGC). However, improvements in hygiene have led to an increase in the prevalence of HP-naïve DGC; that is, DGC that occurs independent of HP. Although multiple genomic cohort studies for gastric cancer have been conducted, including studies for DGC, distinctive genomic differences between HP-exposed and HP-naïve DGC remain largely unknown. Here, we employed exome and RNA sequencing with immunohistochemical analyses to perform binary comparisons between 36 HP-exposed and 27 HP-naïve DGCs from sporadic, early-stage, and intramucosal or submucosal tumor samples. Among the samples, 33 HP-exposed and 17 HP-naïve samples had been preserved as fresh-frozen samples. HP infection status was determined using stringent criteria. HP-exposed DGCs exhibited an increased single nucleotide variant burden (HP-exposed DGCs; 1.97 [0.48-7.19] and HP-naïve DGCs; 1.09 [0.38-3.68] per megabase; p = 0.0003) and a higher prevalence of chromosome arm-level aneuploidies (p < 0.0001). CDH1 was mutated at similar frequencies in both groups, whereas the RHOA-ARHGAP pathway misregulation was exclusive to HP-exposed DGCs (p = 0.0167). HP-exposed DGCs showed gains in chromosome arms 8p/8q (p < 0.0001), 7p (p = 0.0035), and 7q (p = 0.0354), and losses in 16q (p = 0.0167). Immunohistochemical analyses revealed a higher expression of intestinal markers such as CD10 (p < 0.0001) and CDX2 (p = 0.0002) and a lower expression of the gastric marker, MUC5AC (p = 0.0305) among HP-exposed DGCs. HP-naïve DGCs, on the other hand, had a purely gastric marker phenotype. This work reveals that HP-naïve and HP-exposed DGCs develop along different molecular pathways, which provide a basis for early detection strategies in high incidence settings. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Clinical outcomes of palliative treatment for gastric bleeding from incurable gastric cancer.

PURPOSE: Deciding palliative treatment for gastric bleeding from incurable gastric cancer (IGC) is worrying considering different patient situations and the lack of comprehensive assessment of palliative treatment. We evaluated the clinical outcomes and prognostic factors after palliative treatment for gastric bleeding from IGC. METHODS: We enrolled 48 consecutive patients with gastric bleeding from IGC who underwent palliative surgery (PS) or palliative radiotherapy (PRT). RESULTS: Of the 48 patients, 23 underwent PS and 25 received PRT. More patients who had an Eastern Cooperative Oncology Group-Performance Status (ECOG-PS) ≥ 2 or who received chemotherapy underwent PRT than underwent PS. Severe complications were observed in 2 (8.6%) patients after PS. After PRT, 22 patients achieved hemostasis (88%), but rebleeding was found in 10 (40%). Chemotherapy was introduced after palliative treatment for 21 (91.3%) patients in the PS group and 17 (68%) patients in the PRT group. The median survival time (MST) of patients with and without chemotherapy after PS was 12.5 and 3.1 months, respectively (p ≤ 0.001), while the MST of patients with and without chemotherapy after PRT was 6.5 and 1.6 months (p < 0.001). Multivariate analyses identified ECOG-PS, tumor size, and chemotherapy after palliative treatment as independent risk factors. CONCLUSIONS: Palliative treatment strategies for gastric bleeding should be determined with consideration of the general condition, previous chemotherapy, and chemotherapy after palliative treatment.

Prediction of the invasion depth of superficial nonampullary duodenal adenocarcinoma.

OBJECTIVES: Distinguishing between intramucosal cancer and submucosal invasive cancer is vital for optimal treatment selection for patients with superficial nonampullary duodenal adenocarcinoma (SNADAC); however, standard diagnostic systems for diagnosing invasion depth are as yet undetermined. METHODS: Of 205 patients with SNADAC who underwent treatment at our institution between 2006 and 2022, 188 had intramucosal cancer and 17 had submucosal invasive cancer. The clinical, endoscopic, and pathological features used in the preoperative diagnosis of invasion depth and the diagnostic performance of endoscopic ultrasonography (EUS) were retrospectively analyzed in 85 patients. RESULTS: The oral side of the papilla tumor location, protruded or mixed macroscopic type, and moderately-to-poorly differentiated adenocarcinoma based on biopsy specimens were significantly more frequent in submucosal invasive cancer than in intramucosal cancer (88% vs. 48%; 94% vs. 42%; 47% vs. 0%, respectively). From the relationship between the endoscopic features and the submucosal invasive cancer incidence, submucosal invasion risk was stratified as: (i) low-risk (risk, 2%), all lesions located on the anal side of the papilla and superficial macroscopic type on the oral side of the papilla; and (ii) high-risk (risk, 23%), protruded or mixed macroscopic type on the oral side of the papilla. Based on the biopsy specimens, all eight patients with moderately-to-poorly differentiated adenocarcinoma had submucosal invasive cancer. Furthermore, EUS was not associated with invasion depth's diagnostic accuracy improvements. CONCLUSION: Optimal treatment indications for SNADAC can be selected based on the risk factors of submucosal invasion by tumor location, macroscopic type, and biopsy diagnosis.

Clinical characteristics and long-term prognosis of type 1 gastric neuroendocrine tumors in a large Japanese national cohort.

OBJECTIVES: Optimal management of type 1 gastric neuroendocrine tumors (T1-GNETs) remains unknown, with few reports on their long-term prognosis. This study investigated the clinical characteristics and long-term prognosis of T1-GNETs. METHODS: We reviewed the medical records of patients diagnosed with T1-GNET during 1991-2019 at 40 institutions in Japan. RESULTS: Among 172 patients, endoscopic resection (ER), endoscopic surveillance, and surgery were performed in 84, 61, and 27, respectively, including 27, 77, and 2 patients with pT1a-M, pT1b-SM, and pT2 tumors, respectively. The median tumor diameter was 5 (range 0.8-55) mm. Four (2.9%) patients had lymph node metastasis (LNM); none had liver metastasis. LNM rates were significantly higher in tumors with lymphovascular invasion (LVI) (15.8%; 3/19) than in those without (1.1%; 1/92) (P = 0.016). For tumors <10 mm, LVI and LNM rates were 18.4% (14/76) and 2.2% (2/90), respectively, which were not significantly different from those of tumors 10-20 mm (LVI 13.3%; 2/15, P = 0.211; and LNM 0%; 0/17, P = 1.0). However, these rates were significantly lower than those of tumors >20 mm (LVI 60%; 3/5, P = 0.021; and LNM 40%; 2/5, P = 0.039). No tumor recurrence or cause-specific death occurred during the median follow-up of 10.1 (1-25) years. The 10-year overall survival rate was 97%. CONCLUSIONS: Type 1 gastric neuroendocrine tumors showed indolent nature and favorable long-term prognoses. LVI could be useful in indicating the need for additional treatments. ER for risk prediction of LNM should be considered for tumors <10 mm and may be feasible for tumors 10-20 mm. TRIAL REGISTRATION: The study protocol was registered in the University Hospital Medical Information Network (UMIN) under the identifier UMIN000029927.