Claudin18.2 in Advanced Gastric Cancer.

Globally, the fifth most common cancer and the fourth leading cause of cancer-related mortality is gastric cancer (GC). Recent clinical trials on solid tumors enrolled patients who possess druggable genetic alterations, protein expression, and immune characteristics. In gastric or gastroesophageal junction (GEJ) cancers, trastuzumab combined with first-line chemotherapy in human epidermal growth factor receptor 2 (HER2)-positive patients and ramucirumab combined with second-line paclitaxel remarkably prolonged overall survival (OS) compared with chemotherapy alone, according to phase 3 trial results. Recently, immune checkpoint inhibitor (ICI) monotherapy was approved as third- or later-line treatment. Chemotherapy plus ICIs as first-line treatment exhibited improved survival compared with chemotherapy alone in HER2-negative patients according to Checkmate 649 trial results. Conversely, systemic chemotherapy prognosis remains poor. although some patients may achieve durable response to treatment and prolonged survival in advanced GC. Recently, a first-in-class, chimeric immunoglobulin G1 monoclonal antibody (zolbetuximab) that targets and binds to claudin 18 isoform 2 (CLDN18.2) has emerged as a new target therapy in GC treatment. Global phase Ⅲ trials revealed that the addition of zolbetuximab to first-line chemotherapy prolonged OS in CLDN18.2-positive and HER2-negative GC patients. This review summarizes recent clinical trials of CLDN18.2-targeted therapy.

Endoscopic submucosal dissection using an ultrathin endoscope for superficial pharyngeal cancer: a prospective feasibility study (with video).

Background and study aims Endoscopic submucosal dissection (ESD) of pharyngeal cancers with conventional endoscopes often is difficult, not only because of the narrow working space, but also because endoscope maneuverability in the pharynx is poor due to interference from the endotracheal tube and/or hyoid bone. However, we hypothesized that those problems could possibly be resolved by use of an ultrathin endoscope for ESD of superficial pharyngeal cancer. The aim of this prospective interventional study was to investigate the feasibility of ESD for superficial pharyngeal cancer using an ultrathin endoscope. Patients and methods This feasibility study was conducted at NTT Medical Center Tokyo between June 2020 and September 2021, and data from a total of 20 consecutively superficial pharyngeal cancers were analyzed. The primary outcome measure was the R0 resection rate. The ESD completion rate, en bloc resection rate, procedure time, and frequency of intraoperative and postoperative adverse events (AEs) were also evaluated as secondary outcome measures. Results Data from 16 patients with 20 lesions were included in the analysis. All of the lesions were successfully resected by ultrathin endoscope ESD, and the en bloc and R0 resection rates were 100 % and 85.0 % (17/20), respectively; the procedure time was 37.8 ±â€Š28.2 minutes. No intraoperative or postoperative AEs were encountered in any cases. Conclusions ESD using an ultrathin endoscope is feasible for superficial pharyngeal cancers and has potential to be a safe and effective treatment option for these cancers.

Successful esophageal endoscopic submucosal dissection with intraoperative release of stenosis due to previous endoscopic submucosal dissection scarring.

Endoscopic submucosal dissection (ESD) is the standard endoscopic treatment for early esophageal cancer. Esophageal stricture often occurs at the site of ESD for large lesions. When treating a metachronous lesion appearing at the severe stricture, it may be difficult to negotiate a conventional endoscope through the stricture. Using a thin endoscope may be a useful strategy for such lesions, though ESD using a thin endoscope is challenging because of poor maneuverability. Herein, we report a case of successful ESD for early esophageal cancer at the severe stricture, using a conventional endoscope. A 72-year-old man with a previous history of ESD for esophageal cancer and a post-ESD esophageal stricture was referred to our hospital for metachronous early esophageal cancer. The lesion, 10 mm in diameter, was located at the stricture with a slight distal extension. Conventional endoscopes could not be negotiated through stricture. Therefore, submucosal dissection was performed from the oral to the anal aspect of the lesion, as far as possible. After completion of submucosal dissection of the oral aspect of the lesion and part of the lesion located on the stricture, the severe stricture was released, allowing the passage of conventional endoscope, and ESD of the entire lesion was completed en bloc. Histopathological examination showed squamous cell carcinoma, pT1a-LPM. Stricture due to scarring may occur during the regeneration process of the defective mucosa, muscularis mucosa, and submucosal layer. Therefore, incision and dissection of the contracted mucosa, mucularis mucosa, and submucosal layer would release the stenosis.

Safety and Efficacy of Cold Snare Polypectomy Without Submucosal Injection for Large Sessile Serrated Lesions: A Prospective Study.

BACKGROUND & AIMS: Cold snare polypectomy (CSP) has become the standard resection method for small colorectal polyps (<10 mm). Sessile serrated lesions (SSL) have low prevalence of advanced histology irrespective of size, and thus could be amenable to CSP. In this study, we evaluated the safety and efficacy of CSP for SSLs ≥10 mm. METHODS: Between November 2018 and January 2020, we prospectively enrolled 300 consecutive patients who underwent CSP for 474 SSLs ≥10 mm. To delineate SSL borders, indigo carmine chromoendoscopy and/or image-enhanced endoscopy was conducted. Piecemeal CSP (pCSP) was performed in cases where en-bloc resection was difficult. Biopsy specimens were obtained from the margins of the post-polypectomy defect to confirm complete resection. Surveillance colonoscopy was performed to screen for local recurrence. RESULTS: All lesions were successfully resected using CSP without submucosal injection. The median diameter of the resected lesions was 14 mm, and pCSP was used to resect 106 (22%) lesions. Post-polypectomy biopsies revealed residual serrated tissue in only one case (0.2%). Adverse events included immediate bleeding in 8 (3%) patients; no delayed bleeding events occurred, irrespective of the use of antithrombotic drugs. During a 7-month median follow-up period, surveillance colonoscopies were performed for 384 lesions (81%), and no local recurrences were detected. CONCLUSIONS: CSP without submucosal injection is a safe and effective treatment for SSLs ≥10 mm. UMIN Clinical Trials, Number: UMIN000034763.

A new classification for the diagnosis of superficial non-ampullary duodenal epithelial tumors using endocytoscopy: A prospective study.

BACKGROUND AND AIM: Although the frequency of endoscopic diagnosis of superficial non-ampullary duodenal epithelial tumors (SNADETs) has been increasing in recent years, no criteria for the endoscopic diagnosis of these tumors have been established yet. The aim of this study was to assess the usefulness of endocytoscopy for diagnosis SNADETs and to establish new criteria. METHODS: This prospective study was conducted at the NTT Medical Center Tokyo from May 2019 to July 2020, and a total of 100 consecutive SNADETs were enrolled. All the endocytoscopic images of the lesions and surrounding normal mucosa were classified into three groups according to the degree of structural atypia and the nuclear morphology and size. The endocytoscopic diagnoses using endocytoscopic classification was compared with the final histopathological diagnoses. RESULTS: Data of 93 patients with 98 lesions were included in the analysis. The preoperative diagnosis by endocytoscopy coincided with the final histopathological diagnosis in 85 (86.7%) of 98 SNADETs. In addition, the sensitivity and specificity for VCL 4/5 were 87.7% and 85.4%, respectively. In contrast, the accuracy, sensitivity, and specificity of preoperative diagnosis by biopsy were 64.3%, 50.9%, and 82.9%, respectively. Preoperative diagnosis by endocytoscopy showed significantly superior accuracy and sensitivity as compared with preoperative biopsy diagnosis (P < 0.001, respectively). CONCLUSIONS: This new classification (endocytoscopic classification) allows prediction of the tumor histopathology in real time, during endocytoscopy without biopsy, and is expected to be of help in determining the appropriate therapeutic strategies for individual cases of SNADETs. (Clinical trial registration number: UMIN000038643.).

Endoscopic and histological features of Helicobacter pylori-negative differentiated gastric adenocarcinoma arising in the antrum.

BACKGROUND AND AIM: With the increasing prevalence of persons without Helicobacter pylori (HP) infection, cases of HP-negative gastric cancer are increasing. Although rare, cases of differentiated adenocarcinoma of the antrum have been reported in HP-negative patients. We collected cases with such lesions and investigated their endoscopic and histological features. METHODS: Of 1965 consecutive patients with early gastric cancer who underwent endoscopic resection between January 2009 and December 2017, we extracted 9 cases of HP-negative differentiated adenocarcinoma located in the antrum (HPN-DAA). The clinical data, endoscopic findings, and histopathological findings were reviewed. RESULTS: Of the nine patients with HPN-DAA, seven were male, and the median age was 53.8 years. The tumor arose from the pyloric gland mucosa in all cases. According to the endoscopic findings, the lesions were flat-elevated or depressed, mimicking varioliform gastritis. Magnifying endoscopy with narrow-band imaging showed the absence of a clear demarcation line or an irregular microvessel/surface pattern. As for the histopathological findings, eight of the nine lesions were diagnosed as high-grade dysplasia/intraepithelial neoplasia, while the remaining case was diagnosed as tubular adenocarcinoma with submucosal infiltration. The findings of immunohistochemistry confirmed that three cases were of the intestinal mucin phenotype and six were of the mixed gastric and intestinal mucin phenotype. CONCLUSION: HPN-DAA is a very rarely occurring cancer that had never been recognized earlier. They belong to the new category of HP-negative cancers, and there seems to be a certain number of such cases.

Colon cancer of Peutz-Jeghers syndrome with gallolyticus endocarditis.

We report a case of Peutz-Jeghers syndrome with gallolyticus endocarditis which has not yet been reported. Colon cancer was observed and implicated in Peutz-Jeghers syndrome. A 44-year-old female with fever and heart murmur was diagnosed as infective endocarditis caused by streptococcus gallolyticus. After treatment with antibiotics and mitral valbuloplasty, we performed gastrointestinal endoscopic studies and found polyps in stomach and colon. Histological findings of a large pedunculated colon polyp revealed hamartomatous polyp with a lesion of adenocarcinoma with adenoma. She had pigmentation of digits. Her father had also digits pigmentation and died of pancreas cancer. Peutz-Jeghers syndrome with colon cancer was incidentally diagnosed by infective endocarditis and subsequent colonoscopy.