Background/Aims: The safety and efficacy of filgotinib, a once-daily oral Janus kinase 1 preferential inhibitor, were evaluated in Japanese patients with ulcerative colitis (UC) in the phase 2b/3 SELECTION trial. Methods: SELECTION (NCT02914522) was a randomized, placebo-controlled trial comprising 2 induction studies and a maintenance study. Adults with moderately to severely active UC were randomized in induction study A (biologic-naïve) or B (biologic-experienced) to receive filgotinib 200 mg, 100 mg, or placebo once daily for 11 weeks. Patients in clinical remission or Mayo Clinic score response at week 10 entered the 47-week maintenance study. Efficacy and safety outcomes were assessed in Japanese patients enrolled in Japan. Results: Overall, 37 and 72 Japanese patients were enrolled in Japan in induction studies A and B, respectively, and 54 entered the maintenance study. Numerically higher proportions of filgotinib 200 mg-treated than placebo-treated patients achieved clinical remission in induction study A (4/15 [26.7%] vs. 0/6 [0%]) and the maintenance study (5/20 [25.0%] vs. 0/9 [0%]), but not induction study B (1/29 [3.4%] vs. 1/14 [7.1%]). Both doses were well tolerated, and no new safety signals were noted. Herpes zoster was reported in 1 filgotinib 200 mg-treated patient in each of induction study A (2.3%, 1/44) and the maintenance study (5.0%, 1/20). Conclusions These data, alongside those of the overall SELECTION population, suggest the potential of filgotinib 200 mg as a viable treatment option for Japanese patients with UC. Owing to small patient numbers, data should be interpreted cautiously.

Purpose: Although patients with late-onset hypogonadism (LOH) often experience lower urinary tract symptoms (LUTS), LUTS are not generally included in LOH symptoms. No study has examined the direct relation of the Aging Males Symptoms rating scale (AMS) and the International Prostate Symptom Score (IPSS) with the quality of life (QOL) index. We analyzed the relation between the IPSS and QOL index and various factors including the AMS in patients with LOH syndromes. Materials and Methods: This study comprised 1,688 men with LOH symptoms who visited our hospital or affiliated clinic. Factors associated with the IPSS were assessed in terms of age, scores of several questionnaires including the AMS, endocrinological variables, and serum concentration of PSA. Among these same factors, those associated with the QOL index were also evaluated. Finally, the same analyses were repeated in 187 patients with low serum testosterone concentration (<3.0 ng/ mL). Results: In a multivariate analysis using the significant items from the univariate analysis, AMS, age, and Erection Hardness Score correlated significantly with the IPSS. A trend analysis using items other than the AMS as adjustment factors also confirmed the relationship between an increase in QOL index and an increase in AMS. Similar results were obtained in the analysis of patients with low serum testosterone concentration. Conclusions We revealed that the relation of IPSS with the QOL index for LUTS is closely associated with the AMS for LOH, regardless of testosterone level. When patients complain of LOH symptoms, a careful, detailed inquiry into LUTS is required.

Objective: Precursor lesions may be identified in fallopian tube tissue after risk-reducing salpingo-oophorectomy (RRSO) in patients with pathogenic variants of BRCA1/2. Serous tubal intraepithelial carcinoma (STIC) is considered a precursor of high-grade serous carcinoma, whereas the significance of the p53 signature remains unclear. In this study, we investigated the relationship between the p53 signature and the risk of ovarian cancer. Methods: We analyzed the clinicopathological findings and conducted DNA sequencing for TP53 variants of p53 signatures and STIC lesions isolated using laser capture microdissection in 13 patients with pathogenic variants of BRCA1/2 who underwent RRSO and 17 control patients with the benign gynecologic disease. Results: TP53 pathogenic variants were detected significantly higher in RRSO group than control (p<0.001). No difference in the frequency of p53 signatures were observed between groups (53.8% vs 29.4%; p=0.17). TP53 sequencing and next-generation sequencing analysis in a patient with STIC and occult cancer revealed 2 TP53 mutations causing different p53 staining for STICs and another TP53 mutation shared between STIC and occult cancer. Conclusion The sequence analysis for TP53 revealed 2 types of p53 signatures, one with a risk of progression to STIC and ovarian cancer with pathological variants in TP53 and the other with a low risk of progression without pathological variants in TP53 as seen in control.

Objective: The practices pertaining to hereditary breast and ovarian cancer (HBOC) in Japan have been rapidly changing owing to the clinical development of poly(ADP-ribose) polymerase inhibitors, the increasing availability of companion diagnostics, and the broadened insurance coverage of HBOC management from April 2020. A questionnaire of gynecologic oncologists was conducted to understand the current status and to promote the widespread standardization of future HBOC management. Methods: A Google Form questionnaire was administered to the members of the Japan Society of Gynecologic Oncology. The survey consisted of 25 questions in 4 categories: respondent demographics, HBOC management experience, insurance coverage of HBOC management, and educational opportunities related to HBOC. Results: A total of 666 valid responses were received. Regarding the prevalence of HBOC practice, the majority of physicians responded in the negative and required human resources, information sharing and educational opportunities, and expanded insurance coverage to adopt and improve HBOC practice. Most physicians were not satisfied with the educational opportunities provided so far, and further expansion was desired. They remarked on the psychological burdens of many HBOC managements. Physicians reported these burdens could be alleviated by securing sufficient time to engage in HBOC management, creating easy-to-understand explanatory material for patients, collaboration with specialists in genetic medicine, and educational opportunities. Conclusion Gynecologic oncologists in Japan are struggling to deal with psychological burdens in HBOC practice. To promote the clinical practice of HBOC management, there is an urgent need to strengthen human resources and improve educational opportunities, and expand insurance coverage for HBOC management.

BACKGROUND: The canonical Wnt/β-catenin signaling pathway is a fundamental regulatory system involved in various biological events. ICG-001 selectively blocks the interaction of β-catenin with its transcriptional co-activator cyclic AMP response element-binding protein (CBP). Recent studies have provided convincing evidence of the inhibitory effects of ICG-001 on Wnt-driven disease models, such as organ fibrosis, cancer, acute lymphoblastic leukemia, and asthma. However, the effects of ICG-001 in atopic dermatitis (AD) have not been investigated. OBJECTIVE: To investigate whether β-catenin/CBP-dependent signaling was contributed in the pathogenesis of AD and ICG-001 could be a therapeutic agent for AD. METHODS: We examined the effects of ICG-001 in an AD-like murine model generated by repeated topical application of the hapten, oxazolone (Ox). ICG-001 or vehicle alone was injected intraperitoneally every day during the development of AD-like dermatitis arising from once-daily Ox treatment. RESULTS: Ox-induced AD-like dermatitis characterized by increases in transepidermal water loss, epidermal thickness, dermal thickness accompanied by increased myofibroblast and mast cell counts, and serum levels of thymic stromal lymphopoietin and thymus and activation-regulated chemokine, and decreases in stratum corneum hydration, were virtually normalized by the treatment with ICG-001. Elevated serum levels of periostin tended to be downregulated, without statistical significance. CONCLUSION: These results suggest that β-catenin/CBP-dependent signaling might be involved in the pathogenesis of AD and could be a therapeutic target.
Animals ; Asthma ; Chemokine CCL17 ; Cyclic AMP Response Element-Binding Protein ; Cyclic AMP ; Dermatitis ; Dermatitis, Atopic ; Fibrosis ; Mast Cells ; Mice ; Myofibroblasts ; Oxazolone ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Water

OBJECTIVE: The present study investigated long-term outcomes of medroxyprogesterone acetate (MPA) plus metformin therapy in terms of control of atypical endometrial hyperplasia (AEH) and endometrial cancer (EC), and post-treatment conception. METHODS: We retrospectively analyzed 63 patients (42 with EC; 21 with AEH) who underwent fertility-sparing management using MPA plus metformin. MPA (400 mg/day) and metformin (750–2,250 mg/day) were administered to achieve complete response (CR). Metformin was administered until conception, even after MPA discontinuation. RESULTS: Of the total patients, 48 (76%) had a body mass index (BMI) ≥25 kg/m² and 43 (68%) showed insulin resistance. Sixty-one patients (97%) achieved CR within 18 months. CR rates at 6, 8–9, and 12 months were 60%, 84%, and 90%, respectively. During a median follow-up period of 57 months (range, 13–115 months), relapse occurred in 8 of 61 patients (13.1%) who had achieved CR. Relapse-free survival (RFS) in all patients at 5 years was 84.8%. Upon univariate analysis, patients with BMI ≥25 kg/m² had significantly better prognoses than did those with BMI <25 kg/m2 (odds ratio=0.19; 95% confidence interval=0.05–0.66; p=0.009). Overall pregnancy and live birth rates per patient were 61% (19/31) and 45% (14/31), respectively. CONCLUSIONS: MPA plus metformin is efficacious in terms of RFS and post treatment conception. Moreover, metformin may be more efficacious for patients with BMI ≥25 kg/m².
Body Mass Index ; Endometrial Hyperplasia ; Endometrial Neoplasms ; Female ; Fertility Preservation ; Fertilization ; Follow-Up Studies ; Humans ; Insulin Resistance ; Live Birth ; Medroxyprogesterone Acetate ; Metformin ; Pregnancy ; Prognosis ; Recurrence ; Retrospective Studies

OBJECTIVE: Palonosetron is effective for the management of acute and delayed chemotherapy-induced nausea and vomiting (CINV). While emetogenic carboplatin-based chemotherapy is widely used to treat gynecologic cancers, few studies have evaluated the antiemetic effectiveness of palonosetron in this setting. METHODS: A multicenter, single-arm, open-label phase II trial was conducted to evaluate the safety and effectiveness of palonosetron in controlling CINV in patients with gynecologic cancer. Chemotherapy-naïve patients received intravenous palonosetron (0.75 mg/body) and dexamethasone before the infusion of carboplatin-based chemotherapy on day 1. Dexamethasone was administered (orally or intravenously) on days 2–3. The incidence and severity of CINV were evaluated using the patient-completed Multinational Association of Supportive Care in Cancer Antiemesis Tool and treatment diaries. The primary endpoint was the proportion of patients experiencing complete control (CC) of vomiting, with “no rescue antiemetic medication” and “no clinically significant nausea” or “only mild nausea” in the delayed phase (24–120 hours post-chemotherapy). Secondary endpoints were the proportion of patients with a complete response (CR: “no vomiting” and “no rescue antiemetic medication”) in the acute (0–24 hours), delayed (24–120 hours), and overall (0–120 hours) phases, and CC in the acute and overall phases. RESULTS: Efficacy was assessable in 77 of 80 patients recruited. In the acute and delayed phases, the CR rates the primary endpoint, were 71.4% and 59.7% and the CC rates, the secondary endpoint, were 97.4% and 96.1%, respectively. CONCLUSION: While palonosetron effectively controls acute CINV, additional antiemetic management is warranted in the delayed phase after carboplatin-based chemotherapy in gynecologic cancer patients (Trial registry at UMIN Clinical Trials Registry, UMIN000012806).
Antiemetics ; Carboplatin ; Dexamethasone* ; Drug Therapy* ; Female ; Genital Neoplasms, Female ; Humans ; Incidence ; Japan* ; Nausea* ; Vomiting*

BACKGROUND/AIMS: The influences of Helicobacter pylori eradication therapy on the disease course of inflammatory bowel disease (IBD) are still unclear. We therefore conducted a multicenter, retrospective cohort study to evaluate the safety of H. pylori eradication therapy for IBD patients. METHODS: IBD patients with H. pylori eradication from 2005 to 2015 (eradication group) and control patients (non-eradication group; 2 paired IBD patients without H. pylori eradication matched with each eradicated patient) were included. IBD exacerbation (increased/additional IBD drug or IBD-associated hospitalization/surgery) and disease improvement based on the physicians’ global assessment were investigated at baseline, and at 2 and 6 months after eradication or observation. RESULTS: A total of 429 IBD (378 ulcerative colitis, 51 Crohn’s disease) patients, comprising 144 patients in the eradication group and 285 patients in the non-eradication group, were enrolled at 25 institutions. IBD exacerbation was comparable between groups (eradication group: 8.3% at 2 months [odds ratio, 1.76; 95% confidence interval, 0.78–3.92; P=0.170], 11.8% at 6 months [odds ratio, 1.60; 95% confidence interval, 0.81–3.11; P=0.172]). Based on the physicians’ global assessment at 2 months, none of the patients in the eradication group improved, whereas 3.2% of the patients in the non-eradication group improved (P=0.019). Multivariate analysis revealed that active disease at baseline, but not H. pylori eradication, was an independent factor for IBD exacerbation during 2 months’ observation period. The overall eradication rate was 84.0%–comparable to previous reports in non-IBD patients. CONCLUSIONS: H. pylori eradication therapy does not alter the short-term disease activity of IBD.
Clarithromycin ; Cohort Studies ; Colitis, Ulcerative ; Helicobacter pylori* ; Helicobacter* ; Humans ; Inflammatory Bowel Diseases* ; Metronidazole ; Multivariate Analysis ; Retrospective Studies

Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is a chronic inflammatory disease of the gastrointestinal tract, with increasing prevalence worldwide. IBD Ahead is an international educational program that aims to explore questions commonly raised by clinicians about various areas of IBD care and to consolidate available published evidence and expert opinion into a consensus for the optimization of IBD management. Given differences in the epidemiology, clinical and genetic characteristics, management, and prognosis of IBD between patients in Japan and the rest of the world, this statement was formulated as the result of literature reviews and discussions among Japanese experts as part of the IBD Ahead program to consolidate statements of factors for disease prognosis in IBD. Evidence levels were assigned to summary statements in the following categories: disease progression in CD and UC; surgery, hospitalization, intestinal failure, and permanent stoma in CD; acute severe UC; colectomy in UC; and colorectal carcinoma and dysplasia in IBD. The goal is that this statement can aid in the optimization of the treatment strategy for Japanese patients with IBD and help identify high-risk patients that require early intervention, to provide a better long-term prognosis in these patients.
Asian Continental Ancestry Group ; Colectomy ; Colitis, Ulcerative ; Colorectal Neoplasms ; Consensus ; Crohn Disease ; Disease Management* ; Disease Progression ; Early Intervention (Education) ; Epidemiology ; Expert Testimony ; Gastrointestinal Tract ; Hospitalization ; Humans ; Inflammatory Bowel Diseases* ; Japan* ; Prevalence ; Prognosis

Background: We investigated how individual home care services by nurses, care workers, and therapists at patients' homes are related with the continuation of home medical care service provided by medical doctors.Methods: This research retrospectively analyzed primary insured patients registered with the Japanese long-term care insurance system who had newly started using home medical care service, and whose care level was between 1 and 5 according to national long-term care insurance system claims data. We performed multivariable logistic regression analysis to evaluate patients who used home medical care continuously for >3 months and the utilization of each home care service adjusted for patient age, gender, and care level.Results: A total of 26,590 patients were analyzed. Multivariable analysis revealed that the following home care services were associated with longer continuation of home medical care service compared with home medical care alone: day service (OR, 2.10; 95% CI, 1.98-2.23), home help service (1.91; 1.81-2.01), day care including rehabilitation (1.88; 1.69-2.10), home-visit rehabilitation (1.49; 1.31-1.69), and home-visit nursing (1.23; 1.16-1.31).Conclusions: Our results demonstrated a correlation between utilization of home care services and longer continuation of home medical care from the start. These findings may help medical doctors who provide home medical care service collaborate with other home care services by nurses, care workers, and in-home care therapists.