Endoscopic resection for gastric submucosal tumors: Japanese multicenter retrospective study.

OBJECTIVES: Limited information is available on the efficacy and safety of endoscopic resection (ER) of gastric submucosal tumors (SMTs) in Japanese endoscopic practice where ER for gastric tumors is extremely popular. METHODS: We conducted this study to elucidate the current scenario of ER for gastric SMTs in Japanese endoscopic practice. Patients (from 12 institutions) with gastric SMTs who underwent ER were enrolled from the first case until August 2020. RESULTS: We enrolled 117 patients with 118 lesions. The number of patients who underwent ER increased over the years. The mean endoscopic tumor size was 20 ± 7.2 (8-40) mm. The growth type was primarily intraluminal (90%). The mean resection and wound closure times were 58 ± 38 (range, 12-254) min and 31 ± 41 (range, 3-330) min, respectively. Complete ER was achieved for 117 (99%) lesions. Full-thickness resection rate was 44%; however, only 12 (10%) patients required abdominal paracentesis for decompression. Endoscopic treatments were completed in 115 (97%) lesions, while three lesions required conversions to laparoscopic surgery due to luminal collapse, uncontrolled bleeding, and difficulty in defect closure. Gastrointestinal stromal tumors were the most common pathology (74%). No recurrence was observed during the mean follow-up period of 4.3 ± 2.9 years. The 5-year overall survival rate was 98.9% (95% confidence interval 97.8-100%). CONCLUSION: Performance of ER for gastric SMTs is increasing in Japan. The technique seems feasible in Japanese endoscopic practice, warranting further validation in a prospective study.

Gastrointestinal adverse reactions reduce the success rate of Helicobacter pylori eradication therapy: A multicenter prospective cohort study.

BACKGROUND: The screening and treatment of Helicobacter pylori infection for all junior high students in Saga Prefecture, Japan, were started in 2016. The present study aims to evaluate the influence of adverse reactions on the success of the eradication therapy. METHODS: From 2017 to 2019, 25,006 third-grade junior high school students were tested for urinary anti-H. pylori antibodies. Positive cases were confirmed by H. pylori stool antigen tests. Of the 531 students who were found to be H. pylori-positive, 390 (358 in first-line and 32 in second-line therapy) underwent eradication therapy, and 274 (242 in first-line and 32 in second-line) students actually completed a self-reported form to rate stool consistency (based on the Bristol Stool Scale), the maximum number of bowel movements, and abdominal symptoms during the 7 days of treatment. RESULTS: Among the 274 students, the total of primary and secondary eradication success rates was 87% (95% confidential interval: 82.9-90.1) in intention-to-treat analysis. On days 4, 5, and 6, stool consistency was looser in the primary eradication failure group than in the success group (p < .05). Looser stool consistencies were observed in male students with abdominal pain compared to those who did not experience pain (p < .05). Abdominal pain and diarrhea were detected in 28.5% and 42.7% of the subjects, respectively. The overall incidence of other adverse events was low (n = 8/274, 2.9%), and only two students discontinued treatment because of adverse events. CONCLUSIONS: Softening of the stool was related to the eradication failure in the junior high school students, especially in males with abdominal pain. Adverse effects did not induce discontinuation of the eradication treatment.

Effect of probiotics during vonoprazan-containing triple therapy on gut microbiota in Helicobacter pylori infection: A randomized controlled trial.

BACKGROUND: Probiotics are beneficial to patients with Helicobacter pylori infections by modulating the gut microbiota. Biofermin-R (BFR) is a multiple antibiotic-resistant lactic acid bacteria preparation of Enterococcus faecium 129 BIO 3B-R and is effective in normalizing the gut microbiota when used in combination with antibiotics. This study aimed to determine the effect of BFR in combination with vonoprazan (VPZ)-based therapy on gut microbiota. METHODS: Patients with positive urinary anti-H pylori antibody test (primary test) and fecal H pylori antigen test (secondary test) were examined. Patients in group 1 (BFR- ) received VPZ (20 mg twice daily), amoxicillin (750 mg twice daily), and clarithromycin (400 mg twice daily) for 7 days. Patients in group 2 (BFR+ ) received BFR (3 tablets/day) for 7 days, in addition to the aforementioned treatments. Following treatment, the relative abundance, α-diversity, and ß-diversity of gut microbiota were assessed. RESULTS: Supplementation with BFR prevented the decrease in a-diversity after eradication therapy (Day 7). ß-diversity was similar between groups. The incidence rate of diarrhea was non-significantly higher in the BFR- than in the BFR+ group (73.1% vs 56.5%; P = .361). Stool consistency was comparable in the BFR+ group on Days 7 and 1 (3.86 ± 0.95 vs 3.86 ± 1.46; P = .415). CONCLUSION: Biofermin-R combined with VPZ-based therapy resulted in higher microbial α-strain diversity and suppressed stool softening during H pylori eradication therapy.

Assessment of a novel method to detect clarithromycin-resistant Helicobacter pylori using a stool antigen test reagent.

BACKGROUND: The resistance rate of Helicobacter pylori to clarithromycin (CAM) is high among infected children in Japan. Therefore, a new method for detecting CAM-resistant H. pylori using a minimally invasive technique is strongly desired. We aimed to investigate the clinical usefulness of our newly developed nested polymerase chain reaction-quenching probe (Nested PCR-QP) method using stool specimens. METHODS: We first evaluated our method using a residual solution of the H. pylori stool antigen test for adolescents. Then, we evaluated our method using culture testing for adults. RESULTS: Among 57 middle school students with H. pylori, the Nested PCR-QP test results of 53 (90.3%) were able to be analyzed. A total of 28 students had CAM resistance mutations. We found a genetic mutation in 28 students and no mutation in 23 students, and these results were consistent with those of PCR-direct sequencing. In the 23 adults who were diagnosed with H. pylori infection using the rapid urease test and culture testing, we were able to use Nested PCR-QP for analyzing 21 adults who tested positive in the stool H. pylori antigen test. The results obtained for all 21 adults were consistent with those obtained via the drug susceptibility test. CONCLUSIONS: Our novel method could be useful for non-invasively detecting CAM resistance mutations in H. pylori. This may help select a drug to reduce eradication failure rates against H. pylori. Trial registration This study was registered with the University Hospital Medical Information Network Clinical Trials Registry (no. UMIN000030632, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000034977 ) on 29 December 2017.

Evaluation of a Novel Stool Antigen Rapid Test Kit for Detection of Helicobacter pylori Infection.

The Quick Chaser H. pylori (QCP), which is a novel antigen detection kit for Helicobacter pylori, was developed recently. The previous examination kits targeted the catalase of H. pylori; however, this new test kit, to the best of our knowledge, is the first kit to target the flagellar protein of H. pylori The present study aimed to evaluate the efficacy of QCP compared with that of the already commercially available rapid test kit Testmate Rapid Pylori Antigen (TRP). TRP and QCP were utilized in 71 participants. The positive and negative concordance ratios of QCP to TRP were 100% (57/57) and 92.9% (13/14), respectively. Sensitivity based on the rapid urease test and culture test was 92.3%. Results of the dilution sensitivity test showed that QCP was eight times more sensitive to an H. pylori standard strain and the clarithromycin (CAM)-resistant clinical isolate and four times more sensitive to a CAM-susceptible clinical isolate than TRP. For the cross-reactivity test, 27 strains that exist in human feces, such as the Helicobacter genus, Bifidobacterium genus, Lactobacillus genus, and other resident bacteria, were selected. The results obtained using QCP were all negative, and no cross-reaction was observed. In conclusion, compared with TRP, QCP can detect H. pylori using clinical specimens with high sensitivity, regardless of CAM susceptibility and tolerance. No cross-reactivity was observed with other intestinal bacteria in humans. The kit is considered extremely useful in clinical settings.

[Tumor lysis syndrome after FOLFIRI+cetuximab for ascending colon cancer].

We report a case of an 83-year-old woman who developed tumor lysis syndrome (TLS) 5 days after FOLFIRI+cetuximab (Cmab) therapy. A huge ascending colon cancer measuring 10 cm in diameter and with peritoneal dissemination was diagnosed. Following successful therapy with FOLFIRI alone, FOLFIRI+Cmab was administered. On day 5, TLS was diagnosed with hyperuricemia, hyperkalemia, hyperphosphatemia, and an increase in serum creatinine. Intravenous furosemide, volume loading, and glucose-insulin therapy resulted in improvement of laboratory data in 2 days. However, she died on the 34th day due to multiple organ failure caused by aspiration pneumonia following small intestine functional ileus. Although TLS is a rare complication in colon cancer, its onset must be taken into consideration. Also, risk assessment and preventive therapy for TLS should be performed before cancer treatment.

Efficacy and safety of vonoprazan-based regimen for Helicobacter pylori eradication therapy in Japanese adolescents: a prospective multicenter study.

BACKGROUND: Vonoprazan (VPZ)-based regimen for Helicobacter pylori (H. pylori) is safe and more efficacious than the proton pump inhibitor-based regimen mainly in adults. This study aimed to evaluate the efficacy and safety of a VPZ-based regimen for H. pylori eradication therapy in adolescents. METHODS: An H. pylori screening and treatment longitudinal project for third-year junior high school students in Saga Prefecture began in 2016. Students who tested positive for both urine and stool tests received a VPZ-based regimen. On the checklist, students were asked for diarrhea, fever, abdominal pain, nausea, vomiting, urticaria, dysgeusia, or bloody stool occurrence during the therapy. RESULTS: The longitudinal project for H. pylori screening and treatment among third-grade students in Saga Prefecture targeted 41,115 students from 2017 to 2021 and 836 as positive. Of the 645 students, 542 (84.0% in per protocol [PP] analysis and 73.6% in intention-to-treat [ITT] analysis) were successful in primary eradication therapy. The secondary eradication therapy was successful in 79 (96.3% in PP analysis and 76.7% in ITT analysis) of 82 students. In the primary eradication therapy, abdominal pain occurred in 164 (27.9%), diarrhea in 217 (36.9%), nausea or vomiting in 7 (1.2%), and urticaria in 13 (2.2%) students. In the secondary eradication therapy, abdominal pain occurred in 12 (19.4%) and diarrhea in 17 (27.4%) students. The eradication therapy of 5 students was interrupted due to adverse events only by primary eradication therapy. CONCLUSIONS: VPZ-based regimen for H. pylori was efficacious and safe for adolescents, as in adults, for both primary and secondary eradication therapies.

Gut microbiota changes related to Helicobacter pylori eradication with vonoprazan containing triple therapy among adolescents: a prospective multicenter study.

Currently, it is unclear whether treating Helicobacter pylori (H. pylori) infection is safe among adolescents. This study aimed to evaluate the safety of H. pylori eradication therapy by examining gut microbiota changes in adolescents 3 months after the therapy. H. pylori-infected adolescents were enrolled in this study. Their stool samples were collected at the following three time points: before treatment, 1-2 days after completion of treatment, and time of eradication successful judgment. We assessed the relative abundance, alpha-diversity, and beta-diversity of the gut microbiota and adverse events. The number of isolated Actinobacteria decreased immediately after eradication therapy in the 16 students included in the study, and it returned to pretreatment condition at the eradication judgment point. There was no change in the relative abundance at genus level. The alpha-diversity was lost immediately after eradication therapy; however, it recovered at the time of eradication judgment, and it was restored to pretreatment condition. Meanwhile, none of the participants experienced serious adverse events. H. pylori eradication therapy is safe for adolescents with respect to gut microbiota changes associated with H. pylori eradication therapy. Therefore, further long-term evaluations of gut microbiota changes following eradication therapy are warranted.

Jumbo biopsy is useful for the diagnosis of colonic prolapsing mucosal polyps with diverticulosis.

We report here a case of multiple prolapsing mucosal polyps with diverticulosis in the sigmoid colon. A 52-year-old man was admitted to our hospital because of bloody diarrhea. Colonoscopy and barium enema showed multiple diverticula, markedly thickened mucosal folds and polypoid lesions with mucus on the top of them in the sigmoid colon. Endoscopic ultrasonography showed thickening of the mucosal and submucosal layers. Several endoscopic biopsy specimens were taken from the polypoid lesions. Histological examination revealed only chronic inflammatory cell infiltration. In order to obtain a definite diagnosis, we performed endoscopic jumbo biopsy for the polypoid lesions after obtaining informed consent. Histological examination revealed marked lymphocyte infiltration, hemosiderin deposits and fibromuscular obliteration in the lamina propria, features similar to those of mucosal prolapsing syndrome. After anti-diarrhetic treatment, clinical findings were improved. Thus, jumbo biopsy is useful for diagnosis and treatment of prolapsing mucosal polyps.

Adenosquamous pancreatic cancer producing parathyroid hormone-related protein.

An autopsy case of adenosquamous pancreatic cancer in a 61-year-old male patient with an elevated serum level of parathyroid hormone-related protein (PTH-rP) is reported. He was admitted to our hospital with a 1-month-long history of abdominal discomfort and progressive abdominal fullness. A computed tomography (CT) scan of the abdomen showed a retroperitoneal mass, approximately 10 cm in diameter, involving the pancreas, with round enhancement on contrast examination. Histological examination of a specimen taken by CT-guided needle biopsy suggested squamous cell carcinoma or transitional cell carcinoma. Laboratory data on admission revealed a high serum calcium level and high PTH-rP level. The calcium level initially responded to intravenous hydration, furosemide, calcitonin, and bisphosphonates, decreasing from 15.0 to 9.0 mg/dl. However, the hypercalcemia recurred after 10 days. The patient developed carcinomatous peritonitis and acute renal failure, and died on the 25th hospital day. Autopsy revealed a mass in the pancreatic body to tail, invading the retroperitoneum, with progressive carcinomatous peritonitis. Histological examination of the mass revealed infiltrating carcinoma, showing squamous differentiation with focal intracytoplasmic lumina formation, consistent with pancreatic adenosquamous carcinoma. Immunohistological examination showed positive staining for PTH-rP. Adenosquamous carcinoma of the pancreas is relatively rare; only a few cases associated with hypercalcemia and for which PTH-rP has been identified as a causative factor have been reported. This is the first case in which immunohistochemistry proved localized PTH-rP in adenosquamous pancreatic cancer cells, associated with persistent hypercalcemia.