Clinical utility of Todai OncoPanel in the setting of approved comprehensive cancer genomic profiling tests in Japan.

Comprehensive cancer genome profiling (CGP) has been nationally reimbursed in Japan since June 2019. Less than 10% of the patients have been reported to undergo recommended treatment. Todai OncoPanel (TOP) is a dual DNA-RNA panel as well as a paired tumor-normal matched test. Two hundred patients underwent TOP as part of Advanced Medical Care B with approval from the Ministry of Health, Labour and Welfare between September 2018 and December 2019. Tests were carried out in patients with cancers without standard treatment or when patients had already undergone standard treatment. Data from DNA and RNA panels were analyzed in 198 and 191 patients, respectively. The percentage of patients who were given therapeutic or diagnostic recommendations was 61% (120/198). One hundred and four samples (53%) harbored gene alterations that were detected with the DNA panel and had potential treatment implications, and 14 samples (7%) had a high tumor mutational burden. Twenty-two samples (11.1%) harbored 30 fusion transcripts or MET exon 14 skipping that were detected by the RNA panel. Of those 30 transcripts, 6 had treatment implications and 4 had diagnostic implications. Thirteen patients (7%) were found to have pathogenic or likely pathogenic germline variants and genetic counseling was recommended. Overall, 12 patients (6%) received recommended treatment. In summary, patients benefited from both TOP DNA and RNA panels while following the same indication as the approved CGP tests. (UMIN000033647).

Comparison of adjuvant therapies by an H2-receptor antagonist and a proton pump inhibitor after endoscopic treatment in hemostatic management of bleeding gastroduodenal ulcers.

AIM: Upper gastrointestinal bleeding is often associated with a higher risk of serious blood loss. Both H2-receptor antagonists and proton pump inhibitors are commonly given intravenously for endoscopic hemostatic therapies. We compared the effects of a H2-receptor antagonist (famotidine) and a proton pump inhibitor (omeprazole) injected during the early phase (the first 3 days) on cessation of bleeding and prevention of its recurrence in patients who underwent endoscopic therapy for gastroduodenal ulcer bleeding. METHODS: Consecutive patients who were hospitalized at our clinic with bleeding gastroduodenal ulcers and underwent endoscopic therapy were randomly assigned to receive injections of famotidine, omeprazole, or both. Injection of acid suppressants was switched on the fourth day to the oral administration of omeprazole continued for 8 weeks. RESULTS: Over a 25-month period, 116 patients were enrolled. The overall success rate for endoscopic hemostasis was 115/116 (99.1%). The success rate of hemostasis and prevention of recurrent ulcer bleeding by type of acid suppressant following endoscopic hemostasis was 39/40 (97.5%) for Group 1 (3-day omeprazole administration), 35/37 (94.6%) for Group 2 (3-day famotidine administration), and 38/39 (97.4%) for Group 3 (1-day famotidine and then 2-day omeprazole administration), yielding an overall rate of 112/116 (96.6%). No significant difference in the hemostatic effect was observed among the groups. There were also no differences in the duration of hospital days and the number of fasting days between the three groups. CONCLUSION: Famotidine and omeprazole injected during the early phase of a bleeding ulcer may have similar effects to an adjuvant therapy for preventing rebleeding from endoscopically treated upper gastrointestinal bleeding in Japanese patients.

Rikkunshito and 5-HT2C receptor antagonist improve cisplatin-induced anorexia via hypothalamic ghrelin interaction.

Circulating ghrelin concentration regulates appetite behavior, but no study thus far has focused on the role of central ghrelin in anorexia after chemotherapy. To clarify the action mechanisms of rikkunshito (RKT), a traditional Japanese medicine, on cisplatin-induced anorexia, we attempted to elucidate its effect on hypothalamic ghrelin receptor expression in cisplatin-induced anorexia. We first examined the effects of an intracerebroventricular (ICV) injection of exogenous ghrelin on food intake with or without cisplatin treatment, and the effects of cisplatin or m-chlorophenylpiperazine (mCPP), a 5-HT2C receptor agonist, on hypothalamic growth hormone secretagogue receptor 1a (GHS-R1a) mRNA expression. To identify the mechanism of cisplatin-induced decrease in hypothalamic GHS-R1a mRNA expression, we evaluated the effects of SB242084HCl, a 5-HT2C receptor antagonist, and RKT on hypothalamic GHS-R1a gene expression, along with the effect of coadministration of a GHS-R1a antagonist on decreased food intake. Compared to vehicle controls, an ICV-injected rat ghrelin failed to inhibit the decrease in food intake in cisplatin-treated rats. Hypothalamic GHS-R1a gene expression was significantly reduced after cisplatin or mCPP treatment, and the induced decrease was reversed by SB242084HCl or RKT, but not granisetron or ondansetron, both of which are 5-HT3 receptor antagonists. Their suppressive effect on the decrease in food intake was abolished by coadministration of the GHS-R1a antagonist. Administration of RKT or SB242084HCl reversed the decrease in food intake induced by mCPP injection. The improvement by RKT on decreased food intake after cisplatin treatment was partly mediated by hesperidin and isoliquiritigenin, components of RKT. Cisplatin-induced anorexia may worsen because of decreased hypothalamic GHS-R1a gene expression. A 5-HT2C receptor antagonist and RKT suppressed cisplatin-induced anorexia by inhibiting reduction of GHS-R1a signal transduction in the hypothalamus.

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.