Objective: To investigate an association between the gut microbiome and efficacy of poly(ADP-ribose) polymerase inhibitors (PARPi) in ovarian cancer. Methods: This study conducted fecal microbiome analysis (16S rRNA gene sequencing) and circulating tumor DNA (ctDNA) profiling for ovarian cancer patients who underwent PARPi maintenance therapy. Fecal and blood samples were collected at the baseline and the progressive disease (PD) or last follow-up. The relative abundance of gut microbes and progression-free survival (PFS) were analyzed using linear discriminant analysis of effect size and the Cox proportional hazard model according to BRCA1/2 mutation (BRCA1/2mut) status detected by ctDNA sequencing. Results: Baseline samples were available from 23 BRCA1/2mut-positive patients and 33 BRCA1/2mut-negative patients. The microbes enriched in the baseline samples with long PFS were Bifidobacterium, Roseburia, Dialister, Butyricicoccus, and Bilophila for BRCA1/2mut-positive patients and Phascolarctobacterium for BRCA1/2mut-negative patients. In multivariate analyses dividing patients by the median values of relative abundances, no bacteria were associated with PFS in BRCA1/2mut-positive patients, whereas high Phascolarctobacterium abundances (≥1.11%) was significantly associated with longer PFS in BRCA1/2mut-negative patients (median 14.0 vs. 5.9 months, hazard ratio=0.28; 95% confidence interval=0.11–0.69; p=0.014). In the last samples, the relative abundances of Phascolarctobacterium were significantly higher in patients without PD (n=5) than those with PD (n=15) (median 1.25% vs. 0.06%; p=0.016). Conclusion High fecal composition of Phascolarctobacterium was associated with prolonged PFS in patients with BRCA1/2mut-negative ovarian cancer receiving PARPi therapy. Our results would provide new insights for future research.

Objective：Studies on upper extremity functional interventions for patients with spinal cord infarction are limited, and the effectiveness of the interventions for upper limb paresis in such patients have not been elucidated. This case report describes evidence-based spinal cord injury interventions that improved upper extremity function in a patient with spinal cord infarction.Methods：A man in his 60s presented with mild right hemiplegia because of right anterior spinal artery infarction in the C5 medullary segment. Upon admission, the patient had an American Spinal Injury Association Impairment Scale of D, lacked cognitive impairment, and demonstrated independence indoors with ambulation. The intervention included a combination of robotic therapy and electrical stimulation, adherence-enhancing behavioral strategies (Transfer Package), and typical occupational therapy. We recorded the following upper extremity functional scores：①Active Range of Motion of the shoulder, ②Passive Range of Motion of the shoulder, ③Manual Muscle Test, ④Grip strength, ⑤Pinch strength, ⑥Action Research Arm Test, ⑦Simple Test for Evaluating Hand Function, and ⑧Motor Activity Log.Results：After intervention therapy for 39 days, upper extremity function and the degree and quality of arm use in daily activities improved.Conclusion：These results suggest that evidence-based interventions for spinal cord injury could improve upper extremity function and the degree and quality of arm use in daily activities in patients with cervical spinal cord infarction.

Objective：Studies on upper extremity functional interventions for patients with spinal cord infarction are limited, and the effectiveness of the interventions for upper limb paresis in such patients have not been elucidated. This case report describes evidence-based spinal cord injury interventions that improved upper extremity function in a patient with spinal cord infarction.Methods：A man in his 60s presented with mild right hemiplegia because of right anterior spinal artery infarction in the C5 medullary segment. Upon admission, the patient had an American Spinal Injury Association Impairment Scale of D, lacked cognitive impairment, and demonstrated independence indoors with ambulation. The intervention included a combination of robotic therapy and electrical stimulation, adherence-enhancing behavioral strategies (Transfer Package), and typical occupational therapy. We recorded the following upper extremity functional scores：①Active Range of Motion of the shoulder, ②Passive Range of Motion of the shoulder, ③Manual Muscle Test, ④Grip strength, ⑤Pinch strength, ⑥Action Research Arm Test, ⑦Simple Test for Evaluating Hand Function, and ⑧Motor Activity Log.Results：After intervention therapy for 39 days, upper extremity function and the degree and quality of arm use in daily activities improved.Conclusion：These results suggest that evidence-based interventions for spinal cord injury could improve upper extremity function and the degree and quality of arm use in daily activities in patients with cervical spinal cord infarcti.

Tohoku Medical and Pharmaceutical University Hospital uses an information form created by doctors and pharmacists to provide postoperative information to patients who undergo nephrectomy at the Department of Urology. The form recommends that patients' physicians change prescriptions and adjust medication doses considering post-nephrectomy deterioration of renal function in patients with a single remaining kidney. Of the 7 patients who used this information form, prescription changes were made in 4 patients. An information form jointly created by a physician and pharmacist may affect prescription changes.

Background/Aims: The Heart Failure Association (HFA)-PEFF score is recognized as a simple method to diagnose heart failure (HF) with preserved ejection fraction (HFpEF). This study aimed to evaluate the relationship between HFA-PEFF scores and cardiovascular outcomes in HFpEF patients. Methods: A total of 502 consecutive HFpEF patients were prospectively observed for up to 1,500 days. Cardiovascular outcomes were compared between two groups of patients, defined by their HFA-PEFF scores: those who scored 2–4 (the intermediate-score group) and those who scored 5–6 group (the high-score group). Overall, 236 cardiovascular events were observed during the follow-up period (median, 1,159 days). Results: Kaplan-Meier analysis showed that there were significant differences in composite cardiovascular events and HF-related events between the intermediate-score group and the high-score group (p = 0.003 and p < 0.001, respectively). Multivariate Cox proportional hazards analysis showed that the HFA-PEFF scores significantly predicted future HF-related events (hazard ratio, 1.66; 95% confidence interval [CI], 1.11 to 2.50; p = 0.014); receiver operating characteristic analysis confirmed this relationship (area under the curve, 0.633; 95% CI, 0.574 to 0.692; p < 0.001). The cutoff HFA-PEFF score for the identification of HF-related events was 4.5. Decision curve analysis revealed that combining the HFA-PEFF score with conventional prognostic factors improved the prediction of HF-related events. Conclusions HFA-PEFF scores may be useful for predicting HF-related events in HFpEF patients.

Objective: The aim of this study was to establish criteria that would indicate whether fertility preservation therapy would likely be safe for patients aged 40 years or less with endometrioid endometrial cancer based on their DNA methylation profile. Methods: Forty-nine fresh-frozen tissue samples from patients with endometrial cancer from an initial cohort and 31 formalin-fixed paraffin-embedded tissue samples from a second cohort were subjected to genome-wide DNA methylation analysis using the Infinium MethylationEPIC BeadChip. Results: Epigenomic clustering of early-onset endometrial cancer was correlated with the widely used recurrence risk classification. Genes showing differences in DNA methylation levels between the low-recurrence-risk category and intermediate- and high-risk categories were accumulated in pathways related to fibroblast growth factor and nuclear factor-κB signaling. DNA hypomethylation and overexpression of ZBTB38 were frequently observed in the low-risk category. Eight hundred thirty-one marker CpG probes showed area under the curve values of >0.7 on the receiver operating characteristic curve for discrimination of patients belonging to the low-risk category. By combining marker CpG sites, seven panels for placing patients into the low-risk category with 91.3% or more sensitivity and specificity in both the initial and second cohorts were established. Conclusions DNA methylation diagnostics criteria using up to 6 of 8 CpG sites for LPP, FOXO1, RNF4, EXOC6B, CCPG1, RREB1 and ZBTB38 may be applicable to recurrence risk estimation for patients aged 40 years or less with endometrial cancer, regardless of tumor cell content, even if formalin-fixed paraffin-embedded biopsy or curettage materials are used.

Objective: In 2013, a cohort study aimed to clarify the positive and negative effects of introducing the human papillomavirus (HPV) testing for population-based cervical cancer screening has been launched in Japan. This study included four screenings during the subsequent 7-year follow-up period. We aim to describe the results of the first round of this study on cervical cancer screening here. Methods: This study began in September 2013 with recruitment completed in March 2016.Women aged 30–49 years were divided into 2 groups: those who received uterine cervical cytology alone in the first year (control group), or those who received a combination of cytology and HPV testing (intervention group), based on their age. After first screening, women with positive result of cytology or positive HPV test required referral. We summarized the results of the first round of cervical cancer screening. Results: Of the 25,074 women who were eligible for the study, 13,845 women (55.2%) were screened with cytology alone; 11,229 women (44.8%) received a combination of cytology and HPV testing. After screening, 407 women (2.9%) in the control group and 1,003 women (8.9%) in the intervention group required referral, respectively. Adding HPV testing increased referral rate significantly (p<0.001). Conclusion After first screening, introduction of HPV testing appears to contribute to significantly higher referral rates, suggesting that the number of colposcopies as a detailed examination may increase. These preliminary findings suggest that if HPV testing is introduced into screening, medical institutions need to be prepared for an increasing number of follow-up examinations.

To decide the policy to promote palliative care properly, a new questionnaire has been added to Patient’s behavior survey to assess Quality of Life (QOL) of inpatients and outpatients in Japan. The aim of this study was to survey QOL score of general population in Japan by using a questionnaire of patient’s behavior survey. A large nationwide postal survey was conducted from January through February 2013 in Japan. A total of 2400 subjects were selected randomly from among members of the general population who were 20 to 79 years of age and lived in Japan. A total of 978 (41.1%) questionnaires were analyzed, and reference data of QOL score weighted by the national standard value of sex-age group population were calculated. Correlation coefficients were calculated between QOL score and SF-8TM, Patient Health Questionnaire-9 (PHQ-9), Eastern Cooperative Oncology Group Performance Status (ECOG), Memorial Symptom Assessment Scale (MSAS) score. In addition, sociodemographic factors related to QOL score were evaluated. From the perspectives of public health and administrative policy, the results of this survey will provide important basic data to evaluate patient’s behavior survey broadly and continuously with the goal of establishing a palliative care system in Japan.

PURPOSE: Patients with pathological stage T1N+ or T2–3N0 gastric cancer may experience disease recurrence following curative gastrectomy. However, the current Japanese Gastric Cancer Treatment Guidelines do not recommend postoperative adjuvant chemotherapy for such patients. This study aimed to identify the prognostic factors for patients with pT1N+ or pT2–3N0 gastric cancer using a multi-institutional dataset. MATERIALS AND METHODS: We retrospectively analyzed the data obtained from 401 patients with pT1N+ or pT2–3N0 gastric cancer who underwent curative gastrectomy at 9 institutions between 2010 and 2014. RESULTS: Of the 401 patients assessed, 24 (6.0%) experienced postoperative disease recurrence. Multivariate analysis revealed that age ≥70 years (hazard ratio [HR], 2.62; 95% confidence interval [CI], 1.09–7.23; P=0.030) and lymphatic and/or venous invasion (lymphovascular invasion (LVI): HR, 7.88; 95% CI, 1.66–140.9; P=0.005) were independent prognostic factors for poor recurrence-free survival. There was no significant association between LVI and the site of initial recurrence. CONCLUSIONS LVI is an indicator of poor prognosis in patients with pT1N+ or pT2–3N0 gastric cancer.

PURPOSE: To evaluate whether hydrodistention with fulguration of Hunner lesions (HD/FUL) plus maintenance dimethyl sulfoxide (DMSO) therapy prolongs the recurrence-free time in patients with Hunner type interstitial cystitis (IC).METHODS: The study enrolled patients with Hunner type IC who required repeat HD/FUL due to recurrence of IC symptoms after the first HD/FUL at our institution. All patients received a second HD/FUL plus maintenance DMSO therapy. The maintenance DMSO therapy was performed every 2 weeks for a total of 8 instillations, and then once every 4 weeks thereafter. The recurrencefree time from HD/FUL to therapeutic failure was estimated using the Kaplan-Meier method. The recurrence-free time between the first HD/FUL and second HD/FUL plus maintenance DMSO therapy was statistically compared using the log-rank test.RESULTS: A total of 21 patients (mean age, 66.3±10.8 years) with Hunner type IC were evaluated. The recurrence-free time for the second HD/FUL plus maintenance DMSO therapy was significantly longer than that for the first HD/FUL (P<0.0001). The median recurrence-free time for the first HD/FUL was 10.1 months, while that for the second HD/FUL plus maintenance DMSO therapy has yet to be reached. The recurrence-free rate for the first HD/FUL was 81.0% at 6 months, 38.1% at 1 year, 9.5% at 2 years, and 4.8% at 3 years. In contrast, the rate for the second HD/FUL plus maintenance DMSO therapy was 100% at 6 months, 94.7% at 1 year, 82.6% at 2 years, and 82.6% at 3 years. There were no significant differences in efficacy between the first and second HD/FUL.CONCLUSIONS: HD/FUL plus maintenance DMSO therapy clearly prolongs the recurrence-free time compared with HD/FUL alone in Hunner type IC.
Cystitis, Interstitial ; Dimethyl Sulfoxide ; Humans ; Methods ; Pilot Projects ; Recurrence