Objective: This study analyzed the efficacy of add-on atezolizumab to standard first-line bevacizumab-containing therapy in 56 Japanese patients with metastatic and recurrent cervical cancer treated across 8 sites under the Japanese Gynecologic Oncology Group between October 2018 and August 2021 in the BEATcc trial. Methods: Patients were randomized to standard arm (standard therapy: cisplatin 50 mg/m 2or carboplatin area under the curve of 5, paclitaxel 175 mg/m 2 , and bevacizumab 15 mg/kg) or experimental arm (standard therapy with atezolizumab 1,200 mg). Results: Of 56 patients, 30 were in experimental arm vs. 26, standard arm (age: 53.2±12.9 vs.54.7±12.2 years). Median progression-free survival was 15.8 months (95% confidence interval [CI]=10.4–26.1) in experimental arm vs. 11.1 months (8.4–16.5) in standard arm (hazard ratio [HR]=0.51; 95% CI=0.26–1.01). Median overall survival was 34.1 months (23.2–38.6) in the experimental arm vs. 31.6 months (16.4–36.5), standard arm (HR=0.53; 95% CI=0.23–1.21). Objective: response rate was 86.7% in experimental arm vs. 84.6%, standard arm. Complete response and partial response, respectively, were 23.3% and 63.3% in experimental arm and 26.9% and 57.7% in standard arm. Grade ≥3 adverse events occurred in 80.0%, experimental arm and 88.5%, standard arm. Gastrointestinal/genitourinary fistula incidence was lower in Japanese patients (1 patient receiving atezolizumab), likely due to stricter inclusion criteria. Conclusion Overall, add-on atezolizumab enhances the efficacy of bevacizumab and chemotherapy in Japanese patients as those in overall BEATcc population and could be considered a new first-line treatment option for metastatic, persistent, or recurrent cervical cancer in Japan.

Objective: This multi-center retrospective study aimed to clarify the characteristics, diagnostic accuracy, treatment outcomes, and prognostic factors of uterine serous carcinoma (USC) in Japanese women. Methods: The medical records of 193 patients who were treated between 2006 and 2008 at 24 participating institutions in the Japanese Clinical Oncology Group were examined, and pathological slides of 188 patients were re-checked through central pathology review (CPR), hematoxylin-eosin staining, and immunohistochemistry. Results: USC was confirmed in 144 of the 188 (76.6%) patients using CPR, and only 50% were correctly diagnosed preoperatively. Forty-three patients were diagnosed with non-serous carcinoma, whereas one patient had metastasis from another organ. The average age was 65.7 years, and 19% of patients had a history of other cancers. The incidence of stage III–IV disease was 52.8%, and lymph node metastasis was found in 28.5% of patients. Extrauterine spread and distant metastasis occurred in 39% and 14% of patients, respectively. The 2-year overall survival and progression-free survival (PFS) rates were 56% and 42%, respectively. The PFS of patients with stage I and II who underwent complete staging surgery was 92.3%, and that of those without lymph node dissection or omentectomy was 33.3%. Patients with USC had a significantly worse prognosis than 43 patients with non-serous carcinoma. Conclusion USC in Japanese women has characteristics different from those of endometrioid carcinoma, worse prognosis, and is difficult to diagnose preoperatively. Complete surgical staging is necessary even for early-stage disease. Additionally, new adjuvant treatment strategies, including molecular targeted therapy, should be explored.

Epithelial ovarian cancer remains the lethal gynecological malignancy in women. The representative histotype is high-grade serous carcinoma (HGSC), and most patients with HGSC present at advanced stages with peritoneal dissemination. Since the peritoneal dissemination is the most important factor for poor prognosis of the patients, complete exploration for its molecular mechanisms is mandatory. In this narrative review, being based on the clinical, pathologic, and genomic findings of HGSC, chromosomal instability and epigenetic dynamics have been discussed as the potential drivers for cancer development in the fallopian tube, acquisition of cancer stem cell (CSC)-like properties, and peritoneal metastasis of HGSC. The natural history of carcinogenesis with clonal evolution, and adaptation to microenvironment of peritoneal dissemination of HGSC should be targeted in the novel development of strategies for prevention, early detection, and precision treatment for patients with HGSC.

Objective: There have been reports of health hazards caused by medical devices, cosmetics, quasi-drugs, daily necessities, hygiene products, etc. (health-related products) sold in pharmacies and drugstores. However, the role pharmacists play in dealing with the health hazards caused by health-related products has not been clarified. Therefore, we conducted a survey on the cases of health hazards related to health-related products and the views of pharmacists.Methods: A questionnaire was administered anonymously by email to 601 pharmacists working in community pharmacies or drugstores between December 11 and 20, 2019.Results: The number of valid responses was 585. The breakdown of health hazard cases where pharmacists counseled customers were 60 for medical devices, 31 for cosmetics, 18 for quasi-drugs, 9 for hygiene products, and 20 for daily necessities and others. Of those 138 cases, 19 cases of medical devices were estimated to have an intermediate risk as a health hazard, and the other 119 cases were all classified as low. Of the cases that the pharmacists were not approached for help, but were aware of, 57 were medical devices (21 high, 31 intermediate, 5 low), 44 were cosmetics (12 intermediate, 32 low), 12 were quasi-drugs (7 intermediate, 5 low), 7 were hygiene products (7 low), and 64 were daily necessities and others (26 high, 34 intermediate, 4 low). With regard to health-related products, 95% of the respondents indicated that they had responded to customer questions with advice.Conclusion: Our results show that there are various cases that could develop into health hazards due to health-related products, and most respondents felt a need to alert the public. As such, pharmacists and other staffs in drugstores will continue to provide health support functions to their customers by advising them on not only pharmaceuticals but also these health-related products.

Objective：To investigate the lower limb skeletal muscle stiffness in healthy individuals.

Methods：Using ultrasonographic elastography, we measured the degree of stiffness of the rectus femoris and medial head of the gastrocnemius in healthy individuals and investigated the relationships between muscle stiffness and thickness, a quantitative measure of muscles, and between muscle stiffness and brightness, a qualitative measure of muscles. Furthermore, relationships between muscle stiffness and age, body weight, and body mass index (BMI) were also studied.

Results：Rectus femoris stiffness was positively correlated with muscle thickness. Rectus femoris stiffness had a weak negative correlation with muscle brightness and a weak positive correlation with body weight and BMI. Stiffness of the medial head of the gastrocnemius showed no correlation with any of the study variables. Muscle stiffness did not correlate with age in either of the muscles. No sex-related difference was found in the degree of muscle stiffness.

Conclusion：Although rectus femoris stiffness was associated with muscle thickness and brightness, these relationships were not observed for muscle stiffness of the medial head of the gastrocnemius. The data suggested that rectus femoris stiffness reflects the quantitative and qualitative states of the muscle, and the presence of such relationships may depend on the location of the muscle.

Treatment of perianal and vulvar extramammary Paget disease (EMPD), rare intraepithelial malignancies, is often challenging because of its potential to spread into the anal canal. However, there is still no consensus regarding the optimal resection margin within the anal canal. Between 2004 and 2014, six patients (three with perianal EMPD and three with vulvar EMPD) in which the spread of Paget cells into the anal canal was highly suspected were referred to our department. To evaluate the disease extent within the anal canal, preoperative mapping biopsy of the anal canal was performed in five out of six patients. Two patients were positive for Paget cells within the anal canal (one at the dentate line and the other at 0.5 cm above the dentate line), whereas in three patients, Paget cell were present only in the skin of the anal verge. Using 1 cm margin within the anal canal from the positive biopsy sites, we performed anal-preserving wide local excision (WLE), and negative resection margins within the anal canal were confirmed in all five patients. The remaining one patient with perianal EMPD did not undergo mapping biopsy of the anal canal because preoperative colonoscopy revealed that the Paget cells had spread into the lower rectum. Therefore, WLE with abdominoperineal resection was performed. During the median follow-up period of 37.3 months, no local recurrence was observed in all patients. Our small case series suggest the usefulness of mapping biopsy of the anal canal for the treatment of perianal and vulvar EMPD.
Anal Canal* ; Biopsy* ; Colonoscopy ; Consensus ; Follow-Up Studies ; Humans ; Paget Disease, Extramammary* ; Rectum ; Recurrence ; Skin

Treatment of perianal and vulvar extramammary Paget disease (EMPD), rare intraepithelial malignancies, is often challenging because of its potential to spread into the anal canal. However, there is still no consensus regarding the optimal resection margin within the anal canal. Between 2004 and 2014, six patients (three with perianal EMPD and three with vulvar EMPD) in which the spread of Paget cells into the anal canal was highly suspected were referred to our department. To evaluate the disease extent within the anal canal, preoperative mapping biopsy of the anal canal was performed in five out of six patients. Two patients were positive for Paget cells within the anal canal (one at the dentate line and the other at 0.5 cm above the dentate line), whereas in three patients, Paget cell were present only in the skin of the anal verge. Using 1 cm margin within the anal canal from the positive biopsy sites, we performed anal-preserving wide local excision (WLE), and negative resection margins within the anal canal were confirmed in all five patients. The remaining one patient with perianal EMPD did not undergo mapping biopsy of the anal canal because preoperative colonoscopy revealed that the Paget cells had spread into the lower rectum. Therefore, WLE with abdominoperineal resection was performed. During the median follow-up period of 37.3 months, no local recurrence was observed in all patients. Our small case series suggest the usefulness of mapping biopsy of the anal canal for the treatment of perianal and vulvar EMPD.
Anal Canal* ; Biopsy* ; Colonoscopy ; Consensus ; Follow-Up Studies ; Humans ; Paget Disease, Extramammary* ; Rectum ; Recurrence ; Skin

The purpose of the present study was to indicate the relationship between health-related quality of life (HRQOL) measures, the daily rhythm of oral temperature (OT), and lifestyle. Five-hundred young men volunteered to participate in this study. Their OT, measured using a digital thermometer, was recorded every 2h from the time they woke up to the time they went to sleep for 1 week. The daily rhythm of OT was calculated as a quadratic function using the 1-week data. The HRQOL was measured using the Short-Form 36-Item Health Survey version 2 (SF-36v2). The participants were divided into 3 groups: a high-value group (HG) with ≥ 55 points of each summary score and each subscale score, a middle-value group (MG) with score > 45 and < 55 points, and a low-value group (LG) with score ≤ 45 points. Lifestyle was assessed in terms of eating habits, sleeping and exercise, and the presence of unidentified complaints. At the mental component summary, the OT at the time of waking up and the peak OT in the HG were significantly higher than those in the LG. At the physical and mental component summary, lifestyle in the HG was more favorable. These data suggest that the daily rhythms of OT may reflect the mental health status of an individual. The entraining factors in circadian variation might play a role in improving mental health and reducing unidentified complaints. In conclusion, there appears to be an association between mental health status, lifestyle, and daily rhythms of OT.

BACKGROUND: Predictive factors for the efficacy of dipeptidyl peptidase-4 (DPP-4) inhibitors for lowering glycosylated hemoglobin (HbA1c) remain unclear in patients with type 2 diabetes mellitus. The aim of this study is therefore to clarify predictive factors of the efficacy of DPP-4 inhibitors for lowering HbA1c after 12 months of treatment. METHODS: A total of 191 consecutive type 2 diabetic patients (male sex 55%, mean age, 68.3+/-35.8 years), who had been treated with DPP-4 inhibitors for 12 months, were enrolled in this study and evaluated retrospectively. RESULTS: After 12 months of DPP-4 inhibitor treatment, random blood glucose level, and HbA1c level, decreased from 167+/-63 to 151+/-49 mg/dL (P<0.01), and from 7.5%+/-1.3% to 6.9%+/-0.9% (P<0.01) respectively, without severe side effects. Multiple regression analysis showed that predictors of DPP-4 inhibitor treatment efficacy in lowering HbA1c level after 12 months were a decrease in HbA1c level after 3 months of treatment, a high baseline HbA1c level, a low baseline body mass index, and the absence of coronary artery disease. CONCLUSION: Most suitable candidates for treatment with DPP-4 inhibitors are diabetics who are not obese and do not have coronary artery disease. In addition, long-term efficacy of DPP-4 inhibitors can be predicted by decrement of HbA1c after 3 months of treatment.
Blood Glucose ; Body Mass Index ; Coronary Artery Disease ; Diabetes Mellitus ; Diabetes Mellitus, Type 2* ; Dipeptidyl-Peptidase IV Inhibitors ; Hemoglobin A, Glycosylated ; Humans ; Retrospective Studies ; Treatment Outcome

This retrospective study was conducted to confirm the relationship between pre- and postpartum metabolic parameters and postpartum reproductive performance and to clarify seasonal characteristics of the metabolic parameters by using our metabolic profile test (MPT) database of Japanese Black breeding herds. In evaluation 1, MPT databases of blood samples from multiparous cows collected prepartum and postpartum were divided into two groups according to calving interval, and each MPT parameter was compared. In evaluation 2, the same MPT databases used in evaluation 1 were divided into two groups according to the sampling period. Significant differences were found in the prepartal total protein and postpartal gamma-glutamyltransferase in evaluation 1. In evaluation 2, significant differences were found in the prepartal and postpartal total protein, albumin/globulin ratio, and glucose. Clear seasonal differences in MPT results emphasized the usefulness of the MPT in breeding cattle herds fed home-pasture roughage and suggest that unsatisfactory reproductive performance during hot periods reflects inadequate nutritional content of the diet and possible reduced feed intake due to heat stress.
Animals ; Blood Proteins/analysis ; Cattle/*physiology ; Diet/veterinary ; Dietary Fiber/analysis ; Female ; Heat Stress Disorders ; *Metabolome ; Postpartum Period ; *Reproduction ; Retrospective Studies ; Seasons