Effects of activation of an alcohol metabolic gene, cigarette smoking, and alcohol intake on the incidence of metachronous gastric cancer in patients who underwent endoscopic resection for gastric cancer: A multicenter retrospective pilot study.

Background and Aim: Metachronous gastric cancer (GC) frequently occurs in patients who have undergone endoscopic resection (ER) for GC. We evaluated the risk for development of metachronous GC following ER for GC based on genetic polymorphisms for alcohol dehydrogenase-1B (ADH1B) and aldehyde dehydrogenase-2 (ALDH2), as well as alcohol consumption and smoking habits. Methods: We studied 77 patients who underwent ER for GC (median follow-up of 84 months). Genotyping of ADH1B/ALDH2 was performed using saliva sampling. Histories of alcohol consumption and smoking before and after ER and Helicobacter pylori eradication were documented. Results: Multivariate analyses revealed that homozygous slow-metabolizing ADH1B (hazard ratio [HR] = 2.38, P < 0.13), heavy smoking (HR = 2.36, P < 0.09), and cigarette smoking after ER (HR = 2.47, P < 0.10) were not independently associated with the risk of secondary GC development. We analyzed the cessation status of the 38 patients who were classified as heavy smokers before ER based on their smoking habits after the ER and divided them into a cessation group (n = 27, non-smokers after ER) and a non-cessation group (n = 11). Cumulative incidence curves of secondary GC in the cessation and non-cessation groups revealed 5-year incidence rates of 19.0% and 45.0%, respectively (P = 0.02). Conclusion: Continued cigarette smoking, at a high level, may be an important risk factor for the development of metachronous GC. Advice for smoking cessation should be given.

Hepatocellular Carcinoma Rupture after Introducing Lenvatinib: An Autopsy Case Report.

Hepatocellular carcinoma (HCC) hemorrhaging/rupture is a rare adverse effect of lenvatinib, and only limited pathological examinations have been reported. This report presents the case of a 69-year-old man who suffered from cardiac arrest and died 7 days after starting lenvatinib treatment for HCC, with an autopsy subsequently performed. Crack and coagulated blood were observed in the largest tumor. Pathologically, the hemorrhaging area was scattered in nearly all of the HCC lesions, regardless of tumor differentiation. This pathological feature is unusual in normal HCC. Thus, it is believed to have been the effect of lenvatinib.

Effect of switching from tenofovir disoproxil fumarate to tenofovir alafenamide on lipid profiles in patients with hepatitis B.

For long-term treatment of hepatitis B virus (HBV) infection, switching from tenofovir-disoproxil-fumarate (TDF) to tenofovir-alafenamide (TAF) may prevent renal dysfunction and bone loss. However, the precise effects of this switch on the blood lipid profile remain to be clarified. This is an important issue as TDF is known to have effects on both low- and high-density lipids. Therefore, our retrospective multi-center study aimed to evaluate the effects of switching from TDF to TAF on the lipid profile of patients with HBV infection. Samples were obtained prior to the switch from TDF to TAF and at 6-12 months after TAF initiation. In some cases, additional samples obtained pre- and post-TDF administration were available for analysis. Serum cholesterol levels, including oxidized-low-density lipoprotein (LDL) and non-high-density lipoprotein-cholesterol (HDL-c), and the rate of dyslipidemia, according to the NCEP-ATP III lipid risk classification, were analyzed. The data from 69 patients were analyzed, including 33 patients with pre- and post-TDF-initiation serum samples. Total cholesterol (T-chol), HDL-c, LDL-c, non-HDL-c, and oxidized LDL levels increased significantly after switching to TAF. With regard to sequential changes pre- to post-TAF, TDF was associated with significantly lower serum T-chol, HDL-c, and oxidized LDL-c levels, with T-chol, HDL-c, LDL-c, and oxidized LDL-c levels increasing significantly after the switch. The switch from TDF to TAF was also associated with an increase in the rate of dyslipidemia, from 33% to 39%, with an increase in the rate of severe dyslipidemia of 1.4% and 5.8%, based on T-chol and LDL-c levels. Of note, no cases of severe dyslipidemia were detected pre-TAF treatment. As oxidized LDL-c and non-HDL-c are strongly associated with atherosclerosis development, careful monitoring of lipid is needed after switching from TDF to TAF in this clinical population.

Very urgent endoscopic retrograde cholangiopancreatography is associated with early discharge in patients with non-severe acute cholangitis.

BACKGROUND: endoscopic retrograde cholangiopancreatography (ERCP) is a first-line procedure for biliary drainage in patients with acute cholangitis, and there are no studies focused on very urgent ERCP within several hours of hospital arrival. This study aimed to elucidate the use of very urgent ERCP for non-severe acute cholangitis. METHODS: this retrospective observational study included patients with non-severe acute cholangitis who underwent ERCP between April 2011 and June 2020 in our institution. Patients were stratified into three groups based on time to ERCP after hospital arrival: very urgent (≤ 3 hours), urgent (3-24 hours) and elective (> 24 hours). The primary outcome was length of hospital stay (LOS). RESULTS: the study cohort included 291 patients, 168 males (57.7 %), with a median age of 76 (interquartile range, 70-83) years. In all, 47, 196 and 48 patients underwent very urgent, urgent and elective ERCP, respectively. Median LOS in the very urgent, urgent, and elective groups was 12, 14, and 15 days, respectively (Kaplan-Meier method). A shorter LOS was associated with earlier ERCP (log-rank trend test, p = 0.04). The rates of readmission within 30 days of discharge and of adverse events were not significantly different among the three groups. By multivariate analysis, very urgent ERCP was associated with a significantly earlier discharge than urgent and elective ERCP (HR, 0.71, p = 0.04 and HR, 0.47, p < 0.01, respectively). In addition, age ≥ 75 years, pancreatitis, albumin ≤ 2.8 g/dL and two or more ERCP procedures were associated with a significantly longer LOS (HRs < 1, p < 0.05). CONCLUSIONS: very urgent ERCP for non-severe acute cholangitis was associated with early discharge.

A case of Epstein-Barr virus-associated lymphoepithelioma-like carcinoma of the colon.

Lymphoepithelioma-like carcinoma is a poorly differentiated carcinoma with prominent lymphoid infiltration occurring in various organs but is exceedingly rare in the colorectal region. This malignancy is frequently associated with Epstein-Barr virus (EBV). Here we report a case of EBV-associated lymphoepithelioma-like carcinoma of the cecum in an 84-year-old male who presented with occult blood. In situ hybridization for EBV-encoded small RNAs (EBER) in an endoscopic submucosal dissection specimen showed that the tumor consisted of EBER-negative well-differentiated tubular adenocarcinoma and EBER-positive lymphoepithelioma-like carcinoma. Real-time PCR detected 7.16 copies of the EBV genome per cell in a sample microdissected from the latter component. Genotyping analysis demonstrated EBV genotype 1, and viral protein/transcript expression in the tumor showed EBV latency I. Expression of Ephrin receptor A2, a recently reported receptor for EBV, was demonstrated in the tumor cells by immunohistochemistry. To our knowledge, this is the first report of lymphoepithelioma-like carcinoma in the colorectal region showing a definite association with EBV infection.

Feasibility of a modified search, coagulation, and clipping method with and without the use of polyglycolic acid sheets and fibrin glue for preventing delayed bleeding after gastric endoscopic submucosal dissection.

BACKGROUND: Methods have been developed for preventing delayed bleeding (DB) after gastric endoscopic submucosal dissection (GESD). However, none of the methods can completely prevent DB. We hypothesized that DB could be prevented by a modified search, coagulation, and clipping (MSCC) method for patients at low risk for DB and by combining the use of polyglycolic acid sheets and fibrin glue with the MSCC method (PMSCC method) for patients at high risk for DB (antibleeding [ABI] strategy). This study assessed the technical feasibility of this novel strategy. METHOD: We investigated 123 lesions in 121 consecutive patients who underwent GESD in Kushiro Rosai Hospital between April 2018 and January 2020. The decision for continuation or cessation of antithrombotic agents was based on the Guidelines for Gastroenterological Endoscopy in Patients Undergoing Antithrombotic Treatment. RESULTS: Oral antithrombotic agents were administered to 28 patients (22.8%). The en bloc R0 resection rate was 98.4%. The MSCC method and the PMSCC method for preventing DB were performed in 114 and 9 lesions, respectively. The median time of the MSCC method was 16 min, and the median speed (the resection area divided by the time of method used) was 3.6 cm2/10 min. The median time of the PMSCC method was 59 min, and the median speed was 1.3 cm2/10 min. The only delayed procedural adverse event was DB in 1 (0.8%) of the 123 lesions. CONCLUSIONS: The ABI strategy is feasible for preventing DB both in patients at low risk and in those at high risk for DB after GESD, whereas the PMSCC method may be necessary for reduction of time.

Relationships of early esophageal cancer with human papillomavirus and alcohol metabolism.

BACKGROUND: It is well known that an alcohol consumption habit together with inactive heterozygous aldehyde dehydrogenase-2 (ALDH2) is an important risk factor for the development of esophageal squamous cell carcinoma (ESCC). It remains controversial whether human papillomavirus (HPV) infection contributes to the occurrence/development of ESCC. There has been no study in which the relationship between ESCC and HPV in addition to alcohol dehydrogenase-1B (ADH1B) and ALDH2 genotypes was evaluated. AIM: To evaluate relationships between HPV infection and development of esophageal cancer, particularly early esophageal cancer, based on ADH1B/ALDH2 polymorphisms. METHODS: We conducted an exploratory retrospective study using new specimens, and we enrolled 145 patients who underwent endoscopic resection for superficial ESCC and had been observed for more than two years by both physical examination and endoscopic examination in Hokkaido University Hospital. Saliva was collected to analyze genetic polymorphisms of ADH1B/ALDH2. We performed in situ hybridization for resected specimens to detect HPV by using an HPV type 16/18 probe. RESULTS: HPV was detected in 15 (10.3%) of the 145 patients with ESCC. HPV-positive rates in inactive ALDH2*1/*2 and ALDH2*1/*1 + *2/*2 were 10.8% and 9.8%, respectively (P = 1.00). HPV-positive rates in slow-metabolizing ADH1B*1/*1 and ADH1B*1/*2 + *2/*2 were 12.0% and 10.0%, respectively (P = 0.72). HPV-positive rates in the heavy or moderate alcohol consumption group and the light or rare consumption group were 11.1% and 8.7%, respectively (P = 0.68). HPV-positive rates in the heavy smoking group and the light or no smoking group were 11.8% and 8.3%, respectively (P = 0.59). The 3-year incidence rates of secondary ESCC or head and neck cancer after initial treatment in the HPV-positive and HPV-negative groups were 14.4% and 21.4% (P = 0.22), respectively. CONCLUSION: In the present situation, HPV status is considered to be less important than other risk factors, such as alcohol consumption, smoking habit, ADH1B/ALDH2 polymorphisms, and HPV status would therefore have no effect on ESCC risk management.

Long-term outcome of endoscopic resection for intramucosal esophageal squamous cell cancer: a secondary analysis of the Japan Esophageal Cohort study.

BACKGROUND: Prospectively collected long-term data of patients undergoing endoscopic resection for superficial esophageal squamous cell carcinoma (ESCC) are limited. The aim of this study was to determine the prospectively collected long-term outcomes of endoscopic resection for ESCC as a secondary analysis of the Japan Esophageal Cohort (JEC) study. METHODS: Patients who underwent endoscopic resection of intramucosal ESCC at 16 institutions between September 2005 and May 2010 were enrolled in the JEC study. All patients underwent endoscopic examination with iodine staining at 3 and 6 months after resection, and every 6 months thereafter. We investigated clinical courses after endoscopic resection, survival rates, and cumulative incidence of metachronous ESCC. RESULTS: 330 patients (mean age 67.0 years) with 396 lesions (mean size 20.4 mm) were included in the analysis. Lesions were diagnosed as high-grade intraepithelial neoplasia in 17.4 % and as squamous cell carcinoma in 82.6 % (limited to epithelium in 28.4 %, to lamina propria in 55.4 %, and to muscularis mucosa in 16.2 %). En bloc resection was achieved in 291 (73.5 %). The median follow-up period was 49.4 months. Local recurrences occurred in 13 patients (3.9 %) and were treated by endoscopic procedures. Lymph node metastasis occurred in two patients (0.6 %) after endoscopic resection. The 5-year overall, disease-specific, and metastasis-free survival rates were 95.1 %, 99.1 %, and 94.6 %, respectively. The 5-year cumulative incidence rate of metachronous ESCC was 25.7 %. CONCLUSIONS: Our study demonstrated that endoscopic resection is an effective treatment for intramucosal ESCC, with favorable long-term outcomes.