A Retrospective Observational Study on Telemedicine in Prescribing Low-Dose Pills for Patients with Dysmenorrhea.

Introduction: In Japan, telemedicine has gradually expanded due to deregulation in response to the COVID-19 pandemic. However, its current status remains unclear, as it is primarily provided by general practitioners. Meanwhile, telemedicine has begun to be utilized for low-dose estrogen-progestin (LEP) prescriptions for dysmenorrhea. Methods: We conducted a retrospective analysis of medical record data from two gynecology clinics and performed an exploratory evaluation between a group that combined telemedicine and in-person visits during the initial 6 months of LEP treatment, and another group with only in-person visits. Results: After propensity score matching, 89 and 83 patients were eligible for the telemedicine and in-person groups, respectively, with 53 patients in both. The characteristics of both groups were similar after matching. There were no significant differences in the probability of abnormal uterine bleeding during the first 6 months of treatment (25% and 43% in each group; p = 0.064), side effects, or treatment efficacy between the two groups. The withdrawal rate at 6 months was significantly higher in the telemedicine group than in the in-person group (13% and 0%, p = 0.013). The average copayment for patients who covered 30% of the total cost was also significantly higher in the telemedicine group after 1 and 3 months of LEP prescription. Conclusion: The appropriate combination of telemedicine and in-person visits is currently employed in hospital visits, which does not differ significantly from in-person visits. Given the retrospective nature of this study and the limited number of cases, further investigation is necessary in the future.

Survival and reproductive outcomes after fertility-sparing surgery performed for borderline epithelial ovarian tumor in Japanese adolescents and young adults: Results of a retrospective nationwide study.

OBJECTIVE: Epithelial borderline ovarian tumor (BOT) frequently occurs in young women. Because progression-free survival, overall survival, and reproductive function are important outcomes, BOT is often treated by fertility-sparing surgery (FSS). We conducted a Japan-wide study to understand post-FSS prognosis in relation to clinical characteristics and types of FSS performed. METHODS: We analyzed clinical and outcome data pertaining to 531 adolescent and young adult (AYA) patients (aged 15-39 years) who underwent FSS for BOT between 2009 and 2013. RESULTS: Median (range) age was 30 (15-39) years, and median observation time was 70 (2-120) months. The disease was of FIGO stage I in 492 (93%) patients. Histopathologically, tumors were of the mucinous (n = 372, 70%), serous (n = 120, 23%), seromucinous (n = 23, 4%), and other (n = 16, 3%) types. Five-year overall survival was 99.5% among patients with stage I and 100% among those with stage II-IV. Five-year progression-free survival was 96.7% and 69.3%, respectively. Multivariate analysis in cases of stage I showed a positive peritoneal cytology to be a significant risk factor for recurrence (HR, 5.199; p = 0.0188). The post-FSS pregnancy rate was relatively low for patients aged ≥30 years (OR, 0.868; 95% CI, 1.16-3.00; p = 0.0090). CONCLUSION: Post-FFS outcomes in terms of overall and progression-free survival are favorable, especially for AYA patients with stage I BOT. However, the relapse rate is high for patients with FIGO stage II-IV and for those with stage I but a positive peritoneal cytology. A long-term prospective observation is needed before reproductive outcomes can be fully established.

Nationwide survey of fertility preservation in patients with hematological malignancies in Japan.

BACKGROUND: Worldwide, there has been a growing interest in oncofertility issues. In 2017, the Japanese Society of Clinical Oncology published clinical practice guidelines for fertility preservation (FP) in cancer patients. We conducted a questionnaire survey to explore the FP practices among hematologists before the publication of this guideline. METHODS: We sent 427 designated cancer hospitals in Japan a questionnaire about FP treatment for patients with hematological malignancies between January and December 2014. RESULTS: Of these, 137 institutions responded, and 81 (19.0%) were included in the analysis. A total of 324 female and 441 male patients, aged < 40 years, were treated. The percentage of patients informed about FP was higher in patients treated with hematopoietic cell transplant than those without. Female patients were less likely to be informed about FP than male patients. FP was performed in a total of 27 female patients: 20 oocyte cryopreservation, 2 embryo cryopreservation, 3 ovarian tissue cryopreservation, and 2 ovarian shielding during total body irradiation. Sperm cryopreservation was performed in 115 male patients. CONCLUSIONS: Our findings indicate the reality of fertility preservation in 2014, before the guideline were issued. Further studies are warranted to investigate the improvement in fertility preservation since the guidelines were issued.

Clinicopathologic features, treatment, prognosis and prognostic factors of neuroendocrine carcinoma of the endometrium: a retrospective analysis of 42 cases from the Kansai Clinical Oncology Group/Intergroup study in Japan.

OBJECTIVE: We conducted a retrospective, multi-institutional, collaborative study to accumulate cases of neuroendocrine carcinoma of the endometrium, to clarify its clinicopathologic features, treatment, prognosis and prognostic factors to collate findings to establish future individualized treatment regimens. To our knowledge, this is the largest case study and the first study to statistically analyze the prognosis of this disease. METHODS: At medical institutions participating in the Kansai Clinical Oncology Group/Intergroup, cases diagnosed at a central pathologic review as neuroendocrine carcinoma of the endometrium between 1995 and 2014 were enrolled. We retrospectively analyzed the clinicopathologic features, treatment, prognosis and prognostic factors of this disease. RESULTS: A total of 65 cases were registered from 18 medical institutions in Japan. Of these, 42 (64.6%) cases were diagnosed as neuroendocrine carcinoma of the endometrium based on the central pathological review and thus included in the study. Advanced International Federation of Gynecology and Obstetrics stages (stage III and IV) and pure type small cell neuroendocrine carcinoma cases had a significantly worse prognosis. Upon multivariate analysis, only histologic subtypes and surgery were significant prognostic factors. Pure type cases had a significantly worse prognosis compared to mixed type cases and complete surgery cases had a significantly better prognosis compared to cases with no or incomplete surgery. CONCLUSION: Our findings suggest that complete surgery improves the prognosis of neuroendocrine carcinoma of the endometrium. Even among cases with advanced disease stages, if complete surgery is expected to be achieved, clinicians should consider curative surgery to improve the prognosis of neuroendocrine carcinoma of the endometrium.

The Clinical Features of Recurrent Endometrial Cancer in Japan: Chemotherapy Instead of Radiotherapy as Postoperative Adjuvant Treatment.

OBJECTIVE: Chemotherapy is a standard adjuvant treatment after primary surgery for endometrial cancer in Japan. We aimed to characterize the clinical features of recurrent endometrial cancer (REC) patients in Japan. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 112 REC patients who were primarily treated at 1 of 3 university hospitals in Japan from 2005 to 2012. We analyzed overall survival since the first recurrence (R-OS) in accordance with several factors. RESULTS: Median patient age was 64 years. The median follow-up period was 48 months. The distributions of cancer stage and histological subtype lacked distinctive features, and most patients had a high risk for recurrence at the time of the primary surgery. Although approximately 78% of patients received adjuvant chemotherapy, 85/112 patients (76%) experienced recurrence within 2 years after the initial treatment ended. For patients receiving adjuvant chemotherapy, regional lymph node (LN) and distant-site recurrence were more frequent (>40%) than vaginal or intra-abdominal recurrence. Median survival and 5-year R-OS were 27 months and 26.1%, respectively. The R-OS was significantly better for patients aged 65 years or older, those with negative peritoneal cytology at the time of primary surgery, those with recurrence within regional LN (eg, pelvic LN or para-aortic LN under the renal vein) and/or vagina, and those who underwent surgery and/or radiotherapy after recurrence. A multivariate analysis indicated that positive peritoneal cytology, a disease-free interval of less than 12 months, recurrent lesions in 2 or 3 areas, and treatment excluding surgery or radiotherapy were independent predictors of poor prognosis after recurrence. CONCLUSIONS: Adjuvant chemotherapy was insufficient to reduce the incidence of distant recurrence. The prognosis of patients recurred within regional LN and/or vagina was significantly better than that of patients with recurrence in other lesions because of treatment with surgery and/or radiotherapy. The disease-free interval was a significant prognostic factor for REC patients.

Glycan profiling using formalin-fixed, paraffin-embedded tissues: Hippeastrum hybrid lectin is a sensitive biomarker for squamous cell carcinoma of the uterine cervix.

AIM: Glycosylation of proteins is altered in cancer cells and distinctive glycan structures are associated with specific cancers, but little is known about the complete glycan profile of particular tumors. In this study, glycomic analysis of squamous cell carcinoma (SCC) of the uterine cervix was performed to search for useful markers. METHODS: A lectin microarray containing 45 lectins with different binding preferences that covered N- and O-linked glycans was coupled with evanescent field-activated fluorescent detection for glycomic analysis of SCC and normal squamous epithelium (NSE) of the cervix. Formalin-fixed, paraffin-embedded tissue specimens were obtained from 16 patients with uterine cervical cancer. Sections that included both tumor and non-tumor tissues were examined to detect alterations of glycans based on the lectin-binding pattern. RESULTS: Hippeastrum hybrid lectin was found to be a sensitive marker for distinguishing SCC of the cervix from NSE. It was the best lectin for discriminating SCC from other tissues according to receiver-operator curve analysis, as it showed a high sensitivity (81.8%), a high specificity (70.1%), and a large area under the curve (0.8182). Histochemistry confirmed specific cytoplasmic staining of SCC cells by Hippeastrum hybrid lectin, while there was little staining of cervical intraepithelial neoplasia and no staining of NSE. CONCLUSION: The present lectin microarray technique could be applied for tissue-based glycomic analysis of various tumors and for discovery of glycan-related biomarkers.

Combination of irinotecan (CPT-11) and nedaplatin (NDP) for recurrent patients with uterine cervical cancer.

BACKGROUND: The clinical activity of combination of irinotecan (CPT-11) and nedaplatin (NDP) for recurrent patients with uterine cervical cancer was evaluated retrospectively. METHODS: Intravenous CPT-11 was given at 60 mg/m(2) (days 1, 8, 15), followed by NDP 80 mg/m(2) (day 1), every 4 weeks. RESULTS: According to the medical records, 29 cases have received this regimen since 2000. Median age was 57 years (range, 29-80), and performance status (PS) of the patients was 18 cases with PS 0, 10 cases with PS 1, and 1 case with PS 2, respectively. Clinical stage was as follows: 3 cases of stage Ib1, 2 cases of Ib2, 2 cases of IIa, 10 cases of IIb, 8 cases of IIIb, and 4 cases of IVb. There were 27 cases of squamous cell carcinoma and 2 cases of adenocarcinoma. Concerning hematological toxicity of grade 3 or more, neutropenia, leukopenia, and febrile neutropenia were observed in 79.3 %, 96.6 %, and 13.8 % of cases, respectively. For nonhematological toxicity, nausea, anorexia, joint pain, and confusion were observed in only 1 case, respectively, and as a result, in 7 cases chemotherapy was not completed. Among 26 cases with clinically evaluable lesions, there were 7 complete responses, 3 partial responses, 7 stable disease, and 9 progressive disease; the clinical response rate was 38.5 %. Median progression-free survival was 7 months (range, 0-38 months). CONCLUSION: The combination of CPT-11 and NDP seems to be active for patients with recurrent uterine cervical cancer.

Clinical study on the efficacy of fluvoxamine for psychological distress in gynecologic cancer patients.

BACKGROUND: Diagnosis of cancer causes psychological distress. The present study investigated the safety and efficacy of fluvoxamine therapy in gynecologic cancer patients with either adjustment disorder or major depression after cancer was diagnosed. METHODS: Screening with the Hospital Anxiety and Depression Scale (HADS) was conducted at least 2 weeks after notification of the diagnosis of cancer in 214 gynecologic cancer patients hospitalized between January 2007 and December 2008. The HADS cutoff score was set at 11 points or greater. Informed consent to the study was obtained from 10 patients, and fluvoxamine was administered for 8 weeks. As primary end points, the safety and efficacy of fluvoxamine were evaluated using the HADS and the SF-36. As a secondary end point, the Clinical Global Impression was determined. RESULTS: The total HADS score, the anxiety score, and the depression score were significantly reduced after 6, 4, and 6 weeks of treatment, respectively. The SF-36 revealed significant improvement in vitality, mental health, and role (emotional) after 8 weeks of treatment. In the 5 patients with adjustment disorder, only the HADS anxiety score was significantly reduced after 4 weeks. In the 5 patients with major depression, the total HADS score, the anxiety score, and the depression score were significantly reduced after 6, 8, and 6 weeks, respectively. According to the SF-36, the adjustment-disorder groups showed significant improvement in mental health after 8 weeks of treatment, whereas the major-depression group showed significant improvement in vitality and role (emotional) after 8 weeks. No adverse events occurred in any subject. Assessment of the Clinical Global Impression suggested that fluvoxamine improved psychological distress in all 10 subjects. CONCLUSIONS: The present findings suggest that fluvoxamine is useful for alleviating psychological distress, including adjustment disorder and major depression, in gynecologic cancer patients. Management of psychological distress after diagnosis of cancer is important.

Risk factors for perioperative venous thromboembolism: A retrospective study in Japanese women with gynecologic diseases.

BACKGROUND: Patients with gynecologic cancer have a high risk of venous thromboembolism (VTE) like patients with other cancers. However, there is little information on risk factors for VTE during gynecologic surgery and no uniform preventive strategy. Our objectives were to identify risk factors for perioperative VTE in gynecologic patients and establish methods for prevention. METHODS: We analyzed 1,232 patients who underwent surgery at the Department of Obstetrics and Gynecology of St. Marianna University School of Medicine between January 2005 and June 2008. We investigated (1) risk factors for preoperative VTE, (2) use of an inferior vena cava (IVC) filter, and (3) risk factors for postoperative VTE. RESULTS: There were 39 confirmed cases of perioperative VTE (3.17%), including 25 patients with preoperative VTE and 14 with postoperative VTE. Thirty-two patients had cancer and seven patients had benign diseases. Twenty-two of the 32 cancer patients (68.7%) had preoperative VTE, while postoperative VTE occurred in 10 cancer patients. Multivariate analysis indicated that ovarian cancer, tumor diameter ≥10 cm, and previous of VTE were independent risk factors for preoperative VTE. Among ovarian cancer patients, multivariate analysis showed that an age ≥50 years, the presence of heart disease, clear cell adenocarcinoma, and tumor diameter ≥20 cm were independent risk factors for preoperative VTE. The factors significantly related to preoperative VTE in patients with benign disease included previous VTE, age ≥55 years, tumor diameter ≥20 cm, and a history of allergic-immunologic disease. Thirteen of the 25 patients (52%) with preoperative VTE had an IVC filter inserted preoperatively. Postoperative screening (interview and D-dimer measurement) revealed VTE in 14/1,232 patients (1.14%). Multivariate analysis indicated that cancer surgery, a history of allergic-immunologic disease, and blood transfusion ≥2,000 ml were independent risk factors for postoperative VTE. CONCLUSIONS: Perioperative VTE is often fatal and preventive measures should be taken in the gynecologic field, especially when patients have the risk factors identified in this study. Since VTE is often present before surgery, preoperative screening is important and use of an IVC filter should be considered.

Transcription factor POU6F1 is important for proliferation of clear cell adenocarcinoma of the ovary and is a potential new molecular target.

OBJECTIVE: Clear cell adenocarcinoma of the ovary often shows resistance to anticancer agents. It accounts for 20% of epithelial ovarian cancer in Japan versus around 5% in other countries. We investigated new molecules to use when developing molecular-targeting therapy for clear cell adenocarcinoma. METHODS: Reverse transcriptase polymerase chain reaction and Western blot analysis were performed to confirm the expression of POU6F1 in several kinds of cell lines derived from epithelial ovarian carcinoma. Microarray analyses were performed using 2 ovarian cancer microarray data sets available on the Internet. Immunohistochemical staining was also done to confirm both the expression and the localization of POU6F1 using human ovarian epithelial ovarian carcinoma tissue specimens. In addition, the gene cluster located downstream of transcription factor POU6F1 was investigated to analyze its role in the proliferation of clear cell adenocarcinoma of the ovary via the lysophosphatidic acid receptor, a G protein-coupled receptor. Furthermore, RNA interference studies with small interfering RNA (siRNA) were performed to assess the effect of POU6F1 on proliferation of xenograft tumors after injection of clear cell adenocarcinoma cells into nude mice. RESULTS: Expression of POU6F1 at messenger RNA and protein was confirmed in cell lines derived from epithelial ovarian carcinoma. The microarray analyses performed using the 2 ovarian cancer microarray data sets available on the Internet indicated that POU6F1 expression was significantly greater in clear cell adenocarcinoma. Immunostaining confirmed the nuclear localization of POU6F1 in clear cell adenocarcinoma (100%). Exposure to the siRNA for POU6F1 reduced the expression of lysophosphatidic acid receptors, which are G protein-coupled receptors involved in tumor cell proliferation. POU6F1 siRNA dose-dependently suppressed the proliferation of clear cell adenocarcinoma cell lines, and a similar effect was confirmed for tumors transplanted into nude mice. CONCLUSIONS: Clear cell adenocarcinoma shows little response to standard therapy. The results of this study suggested that the transcription factor POU6F1 could be a new molecular target for treatment of this cancer.

POU6F1 is the transcription factor that might be involved in cell proliferation of clear cell adenocarcinoma of the ovary.

Clear cell adenocarcinoma of the ovary often shows resistance to anticancer agents. We investigated new molecules to use when developing molecular-targeting therapy for clear cell adenocarcinoma of the ovary. RMG-I cells without invasive potential and RMG-V cells with invasive potential (derived from clear cell adenocarcinoma of the ovary) were subjected to complementary deoxyribonucleic acid microarray analysis. Caveolin-1, a molecule involved in cellular motility and invasion, showed differing expression between the two cell lines. An RNA interference experiment using the published siRNA for caveolin-1 was carried out. The results showed suppression of RMG-V cell infiltration by siRNA, but proliferation of the cancer cells was also suppressed. In other words, RMG-V cell infiltration may have been suppressed simply because cell proliferation was suppressed by RNA interference. These findings suggested that POU6F1 might be a transcription factor involved in the proliferation of ovarian cancer cells. Clear cell adenocarcinoma of the ovary shows little response to standard therapy. The results of the present study suggest that the transcription factor POU6F1 could be a new molecular target for treatment of this cancer.