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Predicting invasion depth of superficial esophageal squamous cell carcinoma is crucial in determining the precise indication for endoscopic resection because the rate of lymph node metastasis increases in proportion to the invasion depth of the carcinoma. Previous studies have shown a close relationship between microvascular patterns observed by Narrow Band Imaging magnifying endoscopy and invasion depth of the superficial carcinoma. Thus, the Japan Esophageal Society (JES) developed a simplified magnifying endoscopic classification for estimating invasion depth of superficial esophageal squamous cell carcinomas. We conducted a prospective study to evaluate the diagnostic values of type B vessels in the pretreatment estimation of invasion depth of superficial esophageal squamous cell carcinomas utilizing JES classification, the criteria of which are based on the degree of irregularity in the microvascular morphology. Type A microvessels corresponded to noncancerous lesions and lack severe irregularity; type B, to cancerous lesions, and exhibit severe irregularity. Type B vessels were subclassified into B1, B2, and B3, diagnostic criteria for T1a-EP or T1a-LPM, T1a-MM or T1b-SM1, and T1b-SM2 tumors, respectively. We enrolled 211 patients with superficial esophageal squamous cell carcinoma. The overall accuracy of type B microvessels in estimating tumor invasion depth was 90.5 %. We propose that the newly developed JES magnifying endoscopic classification is useful in estimating the invasion depth of superficial esophageal squamous cell carcinoma.

Endoscopic surveillance of Barrett’s esophagus has become a foundation of the management of esophageal adenocarcinoma (EAC). Surveillance for Barrett’s esophagus commonly involves periodic upper endoscopy with biopsies of suspicious areas and random four-quadrant biopsies. However, targeted biopsies using narrow-band imaging can detect more dysplastic areas and thus reduce the number of biopsies required. Several specific mucosal and vascular patterns characteristic of Barrett’s esophagus have been described, but the proposed criteria are complex and diverse. Simpler classifications have recently been developed focusing on the differentiation between dysplasia and non-dysplasia. These include the Japan Esophageal Society classification, which defines regular and irregular patterns in terms of mucosal and vascular shapes. Cancer invasion depth is diagnosed by endoscopic ultrasonography (EUS); however, a meta-analysis of EUS staging of superficial EAC showed favorable pooled values for mucosal cancer staging, but unsatisfactory diagnostic results for EAC at the esophagogastric junction. Endoscopic resection has recently been suggested as a more accurate staging modality for superficial gastrointestinal cancers than EUS. Following endoscopic resection for gastrointestinal cancers, the risk of metastasis can be evaluated based on the histology of the resected specimen. European guidelines describe endoscopic resection as curative for well- or moderately differentiated mucosal cancers without lymphovascular invasion, and these criteria might be extended to lesions invading the submucosa (≤ 500 μm), i.e., to low-risk, well- or moderately differentiated tumors without lymphovascular involvement, and < 3 cm. These criteria were confirmed by a recent study in Japan.

Background Esophageal cancer is the eighth most common cause of cancer mortality in Japan. More than 11,000 people had died from esophageal cancer in 2018. The Japan Esophageal Society has collected the data on patients' characteristics, performed treatment, and outcomes annually. Methods We analyzed the data of patients who had first visited the participating hospitals in 2013. In 2019, the data collection method was changed from an electronic submission to a web-based data collection using the National Clinical Database (NCD). Japanese Classification of Esophageal Cancer 10th by the Japan Esophageal Society (JES) and UICC TNM Classification 7th were used for cancer staging Results A total of 8019 cases were registered from 334 institutions in Japan. Squamous cell carcinoma and adenocarcinoma accounted for 87.8% and 6.3%, respectively. The 5-year survival rates of patients treated using endoscopic resection, concurrent chemoradiotherapy, radiotherapy alone, or esophagectomy were 88.3%, 32.4%, 24.4%, and 59.3%, respectively. Esophagectomy was performed in 4910 cases. The operative and the hospital mortality rates were 0.77% and 1.98%, respectively. The survival curves showed a good discriminatory ability both in the clinical and pathologic stages by the JES system. The 5-year survival rate of patients with pStage IV in the UICC classification that included patients with supraclavicular node metastasis was better than that of patients with pStage IVb in JES classification. Conclusion We hope this report contributes to improving all aspects of the diagnosis and treatment of esophageal cancer in Japan.

The options for first-line treatment of advanced oesophageal squamous cell carcinoma are scarce, and the outcomes remain poor. The anti-PD-1 antibody, tislelizumab, has shown antitumour activity in previously treated patients with advanced oesophageal squamous cell carcinoma. We report interim analysis results from the RATIONALE-306 study, which aimed to assess tislelizumab plus chemotherapy versus placebo plus chemotherapy as first-line treatment for advanced or metastatic oesophageal squamous cell carcinoma. This global, randomised, double-blind, parallel-arm, placebo-controlled, phase 3 study was conducted at 162 medical centres across Asia, Europe, Oceania, and North America. Patients (aged ≥18 years) with unresectable, locally advanced, recurrent or metastatic oesophageal squamous cell carcinoma (regardless of PD-L1 expression), Eastern Cooperative Oncology Group performance status of 0–1, and measurable or evaluable disease per Response Evaluation Criteria in Solid Tumours (version 1.1) were recruited. Patients were randomly assigned (1:1), using permuted block randomisation (block size of four) and stratified by investigator-chosen chemotherapy, region, and previous definitive therapy, to tislelizumab 200 mg or placebo intravenously every 3 weeks on day 1, together with an investigator-chosen chemotherapy doublet, comprising a platinum agent (cisplatin 60–80 mg/m2 intravenously on day 1 or oxaliplatin 130 mg/m2 intravenously on day 1) plus a fluoropyrimidine (fluorouracil [750–800 mg/m2 intravenously on days 1–5] or capecitabine [1000 mg/m2 orally twice daily on days 1–14]) or paclitaxel (175 mg/m2 intravenously on day 1). Treatment was continued until disease progression or unacceptable toxicity. Investigators, patients, and sponsor staff or designees were masked to treatment. The primary endpoint was overall survival. The efficacy analysis was done in the intention-to-treat population (ie, all randomly assigned patients) and safety was assessed in all patients who received at least one dose of study treatment. The trial is registered with ClinicalTrials.gov, NCT03783442. Between Dec 12, 2018, and Nov 24, 2020, 869 patients were screened, of whom 649 were randomly assigned to tislelizumab plus chemotherapy (n=326) or placebo plus chemotherapy (n=323). Median age was 64·0 years (IQR 59·0–69·0), 563 (87%) of 649 participants were male, 86 (13%) were female, 486 (75%) were Asian, and 155 (24%) were White. 324 (99%) of 326 patients in the tislelizumab group and 321 (99%) of 323 in the placebo group received at least one dose of the study drug. As of data cutoff (Feb 28, 2022), median follow-up was 16·3 months (IQR 8·6–21·8) in the tislelizumab group and 9·8 months (IQR 5·8–19·0) in the placebo group, and 196 (60%) of 326 patients in the tislelizumab group versus 226 (70%) of 323 in the placebo group had died. Median overall survival in the tislelizumab group was 17·2 months (95% CI 15·8–20·1) and in the placebo group was 10·6 months (9·3–12·1; stratified hazard ratio 0·66 [95% CI 0·54–0·80]; one-sided p<0·0001). 313 (97%) of 324 patients in the tislelizumab group and 309 (96%) of 321 in the placebo group had treatment-related treatment-emergent adverse events. The most common grade 3 or 4 treatment-related treatment-emergent adverse events were decreased neutrophil count (99 [31%] in the tislelizumab group vs 105 [33%] in the placebo group), decreased white blood cell count (35 [11%] vs 50 [16%]), and anaemia (47 [15%] vs 41 [13%]). Six deaths in the tislelizumab group (gastrointestinal and upper gastrointestinal haemorrhage [n=2], myocarditis [n=1], pulmonary tuberculosis [n=1], electrolyte imbalance [n=1], and respiratory failure [n=1]) and four deaths in the placebo group (pneumonia [n=1], septic shock [n=1], and unspecified death [n=2]) were determined to be treatment-related. Tislelizumab plus chemotherapy as a first-line treatment for advanced or metastatic oesophageal squamous cell carcinoma provided superior overall survival with a manageable safety profile versus placebo plus chemotherapy. Given that the interim analysis met its superiority boundary for the primary endpoint, as confirmed by the independent data monitoring committee, this Article represents the primary study analysis. BeiGene.

Endoscopic submucosal dissection (ESD) has been widely used to treat superficial esophageal cancer. The advantages of esophageal ESD include a high en bloc resection rate and accurate pathological diagnosis. It enables local resection of the primary tumor and accurate identification of the risk factors for lymph node metastasis, including depth, vascular invasion, and types of invasion. Even in cases with clinical T1b-SM cancer, ESD and additional treatment can achieve radical cure, depending on the risk of lymph node metastasis. Esophageal ESD will be increasingly vital in minimally invasive and effective esophageal cancer treatment. This article describes the current status and prospects of esophageal ESD.

BackgroundWhile endoscopic submucosal dissection (ESD) is recognized as a minimally invasive standard treatment for differentiated early gastric cancers (EGCs), it has not been indicated for undifferentiated EGC (UD-EGC) because of a relatively high risk of lymph node metastasis (LNM). However, patients with surgically resected mucosal (cT1a) UD-EGC ≤ 2 cm in size with no lymphovascular invasion or ulceration are reported to be at a very low risk of LNM. This multicenter, single-arm, confirmatory trial was conducted to evaluate the efficacy and safety of ESD for UD-EGC.MethodsThe key eligibility criteria were endoscopically diagnosed cT1a/N0/M0, single primary lesion, size ≤ 2 cm, no ulceration and histologically proven components of undifferentiated adenocarcinoma on biopsy. Based on the histological findings after ESD, additional gastrectomy was indicated if the criteria for curative resection were not satisfied. The subjects of the primary analysis were patients with UD-EGC as the dominant component. The primary endpoint was 5-year overall survival (OS) of patients with UD-EGC.ResultsThree hundred 46 patients were enrolled from 49 institutions. The proportion of en bloc resection was 99%. No ESD-related Grade 4 adverse events were noted. Delayed bleeding and intraoperative and delayed perforation occurred in 25 (7.3%), 13 (3.8%), and 6 (1.7%) patients, respectively. Among the 275 patients who were the subjects of the primary analysis, curative resection was achieved in 195 patients (71%), and 5-year OS was 99.3% (95% CI: 97.1–99.8).ConclusionsESD can be a curative and less invasive treatment for UD-EGC for patients meeting the eligibility criteria of this study.

BackgroundIn Japan, the incidence of esophageal adenocarcinoma (EAC) and esophagogastric junction (EGJ) adenocarcinoma is expected to increase and that of gastric adenocarcinoma (GAC) is expected to decrease due to Westernization of the diet and the decreasing prevalence of Helicobacter pylori infection. However, few reports about these trends have included the latest data, and no reports about the time trend in the incidence of EGJ adenocarcinoma have focused on the etiologies (gastric cardia adenocarcinoma or EAC, including Barrett’s adenocarcinoma). We therefore investigated the time trends in the incidence of these cancers by including the latest data.MethodsFirst, we investigated the time trends in EAC and GAC using population-based cancer registry data in Osaka Prefecture (1985–2014). We then investigated the time trend in superficial EGJ adenocarcinoma with clinicopathological features at Osaka International Cancer Institute (2006–2017).ResultsFrom 1985 to 2014 in Osaka Prefecture, the incidence of EAC gradually increased in both sexes, while that of GAC in men did not significantly change and that in women decreased. The ratio of the EAC/GAC incidence increased 3.5 times in men and 1.8 times in women. In the secondary time trend survey for EGJ adenocarcinoma, the numbers of patients with endoscopic Barrett’s esophagus and those without gastric mucosal atrophy increased, and the number of patients with lesions located above the EGJ line and histologically diagnosed as Barrett’s adenocarcinoma increased.ConclusionsThe incidence of EAC and superficial EGJ adenocarcinoma with characteristics similar to those of EAC, including Barrett’s adenocarcinoma, might be increasing.

BackgroundIn elderly patients with superficial esophageal squamous cell carcinoma (ESCC), the optimal treatment strategy after non-curative endoscopic submucosal dissection (ESD) remains unclear. We aimed to evaluate the validity of additional treatments after non-curative ESD and post-ESD survival predictors in elderly patients with ESCC.MethodsElderly patients (age > 75 years) treated with ESD for ESCC between January 2010 and July 2014 at six tertiary referral hospitals in Japan were retrospectively investigated and stratified according to lymph node metastasis risk, based on histological findings (high-risk factors: positive lymphovascular invasion, submucosal invasion, and positive/indeterminate vertical margin) and post-ESD treatment strategy: group A (287 patients; low risk), group B (41 patients; high risk, without additional treatment), and group C (32 patients; high risk, with additional treatment). We evaluated 3- and 5-year overall survival and disease-specific survival, and prognostic factors for post-ESD survival.ResultsAt a median follow-up of 38, 40, and 49 months, respectively, there was 1 esophageal cancer-related death in group A, 1 in group B, and none in group C, whereas 22, 9, and 3 patients in groups A, B, and C died of other diseases. The groups differed significantly in overall survival (92.4%; 87.6%; 93.4%, p = 0.022), although not in disease-specific survival (99.4%; 96.3%; 100%, p = 0.217). On multivariate analysis, Charlson Comorbidity Index (CCI) ≥ 2 was the only independent risk factor for post-ESD death (hazard ratio 7.92; 95% confidence interval 3.42–18.3; p < 0.001).ConclusionsA follow-up strategy without additional treatment after ESD for ESCC may be acceptable in high-risk elderly patients, especially for CCI ≥ 2.