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Ryo Tamura, Ikunosuke Tsuneki, Toru Yanase Department of Obstetrics and Gynecology, Niigata City General Hospital, Niigata, Japan Abstract: We have reported good control of atypical genital bleeding when using a cyclic administration of dienogest (repeated 4-week cycles, each consisting of the administration of 2 mg/day of dienogest for 3 weeks, followed by 1 week of drug withdrawal) in patients with endometriosis. Herein, we report the effectiveness of the long-term cyclic administration (22 months) of dienogest in a case of pathological disappearance of intestinal endometriosis diagnosed by endoscopy and histology of the lower gastrointestinal tract. There is no recurrent sign after 16 months of the treatment being stopped. Atypical genital bleeding during treatment was 3–5 days a month in each cycle. Compliance was good, so we could continue the therapy. The long-term cyclic administration of dienogest in patients with intestinal endometriosis may have significant merit. Keyword: atypical genital bleeding, dysmenorrhea, drug compliance, endoscopy, histology

This clinical image presents a report on the diagnosis and treatment of anti-NMDAR encephalitis, a rare disease. This report emphasizes the importance of a differential diagnosis for acute psychiatric symptoms. Accurate and timely diagnosis is critical for the selection and implementation of treatment and for optimal patient outcomes., Competing Interests: The authors declare that they have no current financial arrangements or affiliations with any organization that may have a direct influence on their work., (© 2022 The Authors. Clinical Case Reports published by John Wiley & Sons Ltd.)

This report presents an unusual case of multiple paraovarian cysts that required emergency surgery due to a paraovarian cyst being entrapped by another paraovarian cyst. Laparoscopic surgery is considered useful for diagnostic and therapeutic purposes and is, therefore, recommended owing to difficulty in differentiating paraovarian cysts from ovarian cysts., Competing Interests: The authors declare that they have no current financial arrangement or affiliation with any organization that may have a direct influence on their work., (© 2022 The Authors. Clinical Case Reports published by John Wiley & Sons Ltd.)

This clinical image presents an unusual report of simultaneous laparoscopic resection of a hydrocele of the canal of Nuck and an ovarian tumor. Laparoscopic treatment with a proper approach is a useful technique in some cases., Competing Interests: The authors declare that they have no current financial arrangement or affiliation with any organization that may have a direct influence on their work., (© 2022 The Authors. Clinical Case Reports published by John Wiley & Sons Ltd.)

To evaluate the outcomes of patients treated with cyclic administration of dienogest after ovarian endometriotic cystectomy, following the completion of treatment. We retrospectively evaluated 26 patients treated with dienogest (2 mg/day) after cystectomy (revised American Society for Reproductive Medicine [r-ASRM] stage III-IV) in a pilot study. Dienogest was administered cyclically, for a total of six cycles, each comprising three weeks on and one week off. Outcomes of interest included severity of menstrual pain and recurrence of cysts at baseline, during the immediate post-treatment period and at the final outpatient follow-up. The mean outpatient follow-up period was 45.0 months. The visual analog scale score for menstrual pain following 6 cycles of dienogest treatment was significantly lower than that at baseline; it remained low at the final follow-up. The recurrence rates of cysts were 4% and 21% at 24 and 48 months after the completion of dienogest treatment, respectively. Six patients with recurrent disease were all classified as having r-ASRM stage IV. Our results suggest that cyclic dienogest for six months after cystectomy could relieve menstrual pain and reduce the recurrence of cysts, for approximately four years. The necessary treatment period for patients with r-ASRM stage IV disease requires further study.

Objective: This study assessed the relief of uterine bleeding and clinical symptoms during cyclic administration of dienogest for the treatment of endometriosis., Methods: In total, 25 patients undergoing ovarian cyst enucleation and given dienogest participated in this study. Dienogest 2 mg/day was administered for 3 weeks, and the drug was then withdrawn for 1 week (cyclic administration of dienogest). This 4-week cycle was repeated six times. Patients' records were prospectively analyzed for the number of days on which any uterine bleeding occurred, as well as menstrual pain before and after the start of dienogest administration were evaluated with a view to using the data obtained herein as the basis., Results: During the period of cyclic administration of dienogest, uterine bleeding occurred on 5.8 to 7.7 days per 4-week period on an average through cycles. Of uterine bleeding episodes, menstruation-like uterine bleeding was present in about 80% of patients. The visual analog scale (VAS) value for menstrual pain significantly decreased from 3.8 before dienogest administration after surgery to 1.5 at the completion of cycle 1, VAS remained low thereafter., Conclusion: These results raise the possibility that cyclic administration of dienogest may relieve lessen uterine bleeding, a major adverse event and menstrual pain.

Obesity is increasingly becoming associated with increased risk of atherosclerosis. Serum levels of the bile acid deoxycholic acid (DCA) are elevated in mice with obesity induced by a high-fat (HF) diet. Therefore, we investigated the influence of DCA on the functions of vascular smooth muscle cells (VSMCs) because the initiation and progression of atherosclerosis are associated with VSMC proliferation and migration. DCA induced c-jun N-terminal kinase (JNK) activation whereas a JNK inhibitor prevented DCA-induced VSMC proliferation and migration. Based on these findings, we examined whether DCA promotes the expression of platelet-derived growth factor β-receptor (PDGFRβ) that has a c-Jun binding site in its promoter region. The mRNA and protein expression levels of PDGFRβ were upregulated in VSMCs after a 24- and 48-h incubation with DCA, respectively. The effects of PDGF such as proliferation and migration of VSMCs were promoted after a 48-h incubation with DCA despite the absence of DCA during PDGF stimulation. These findings suggest that elevated serum concentrations of DCA are involved in the pathogenesis of atherosclerosis in HF-induced obesity.

Objective: Taste disturbance is known to occur as one of the adverse events associated with chemotherapy for gynecological cancer, but few studies have attempted to assess it in practical terms. Therefore, a range of taste tests was performed in gynecological cancer patients., Methods: The patients were 23 women with gynecological cancer being treated with anticancer agents. Subjective symptoms of altered taste were classified, and objective findings were obtained with the following four gustatory tests: serum trace element (zinc, copper, iron) levels, tongue cultures, electrogustometry, and the filter paper disc tests., Results: Of the 23 subjects, 11 perceived taste disturbances. The serum zinc level was consistently below the lower limit of normal. On tongue cultures, indigenous bacteria were seen in all patients during the entire treatment period. Electrogustometry revealed a tendency for the development of hypogeusia in the chorda tympani nerve field. Conversely, hypergeusia tended to develop gradually in the greater petrosal nerve field. The filter paper disc test revealed a tendency for the development of hypergeusia for sweetness, saltiness, and sourness in the chorda tympani nerve field. Hypogeusia for bitterness tended to develop with increasing number of chemotherapy cycles. The glossopharyngeal nerve field exhibited the same tendencies as observed in the chorda tympani nerve field. In the greater petrosal nerve field, there was a tendency for the development of hypergeusia for sweetness, sourness, and bitterness., Conclusions: Abnormal test results were seen in half of patients after cancer chemotherapy., (© 2013.)

The subject was a 75-year-old female who was receiving paclitaxel and carboplatin(TC)chemotherapy every other week after surgery for ovarian cancer. She greatly complained of taste disorders after four cycles(of every other week administration) of TC chemotherapy. To understand how the taste disorder was caused by chemotherapy objectively, taste examinations were conducted for the patient in our department. These examinations were conducted after receiving the informed consent from the patient. The authors conducted taste examinations for the patient using serum zinc measurement, tongue cell culture, electrogustometry, and filter paper disc tests(before and after starting chemotherapy), and found that her serum zinc level fell significantly after four cycles of chemotherapy. Orally disintegrating tablets of polaprezinc were then administered to the patient, after which the subjective symptom of taste disorder improved. Her serum zinc level increased, and the electrogustometric threshold rapidly fell(an improvement). The filter paper disc test showed some improvement, particularly in the glossopharyngeal nerve and the greater petrosal nerve field.

Although primary carcinoid tumor of the ovary is an extremely rare neoplasm, survival is excellent if the disease is confined to one ovary. Herein, we present a case of primary strumal carcinoid tumor of the ovary, stage IA, borderline malignancy, in a 34-year-old woman. Histological findings of the right ovary indicated higher atypical nuclei, higher mitotic rate and focal necrosis of tumorous cells in some areas, findings that are compatible with atypical carcinoid of the lung. Immunohistochemical staining was positive for synaptophysin, neuron-specific enolase, chromogranin A, Ki-67, topoisomerase IIalpha, peptide YY, and thyroglobulin. Three and a half years postoperatively, multiple bone and breast metastases were found and anticancer chemotherapy was ineffective. The results in the present case indicate that an ovarian carcinoid tumor found to be 'atypical carcinoid' according to pulmonary carcinoid criteria or immunohistochemical staining (i.e. highly positive for topoisomerase IIalpha and Ki-67) may have a poor prognosis.

Calcium transfer from the mother to the infant during pregnancy and lactation plays an extremely important role in the bone health of the mother and neonate. Calcium aids in bone health through all ages but is especially crucial during pregnancy and lactation. Changes in the structure and metabolism of bone during pregnancy and the early stage of postpartum are evaluated by investigating bone mineral density (BMD), bone histomorphometry and bone markers of human or animal models. The bone resorption increased at the end of pregnancy and lactation, and the bone formation increases and the bone structure is almost recovered after cessation of lactating in postpartum. Puerperal BMD remained static over the subsequent 5-10 years. If the women have a low BMD at this stage of their reproductive life, it tends not to improve over this time. Perhaps identification of this at-risk group may lead to effective interventions to reduce fracture risk in later life.

Background: To evaluate the frequency of tumor cell contamination in autologous peripheral-blood progenitor cells from patients with ovarian cancer, and to determine the impact of infusing such cells on relapses after high-dose chemotherapy., Methods: Seventy-three samples of peripheral-blood progenitor cells from 24 ovarian cancer patients were studied for contaminated tumor cells by cytokeratin 7 and cytokeratin 20 reverse transcriptase polymerase chain reaction., Results: Tumor cell contamination in peripheral-blood progenitor cells was detected in 11 of 24 patients (46%) and, among these, in four of 11 patients who received transplantations of peripheral-blood progenitor cells. There was no trend towards longer relapse-free survival in patients infused with cytokeratin-negative peripheral-blood progenitor cells as compared with positive ones. Interestingly, two of four patients who received transplantations of peripheral-blood progenitor cells containing tumor cells were free from progression at 20 and 41 months after transplantation., Conclusion: Tumor cell contamination of peripheral-blood progenitor cells was frequently noted by transcriptase polymerase chain reaction in patients with ovarian cancer. The biological and clinical significance of this finding remains to be elucidated.

Objective: The goal of this work was to evaluate response rate, toxicity, and survival in treatment with intraarterial 5-fluorouracil (5-FU) and cisplatin in a neoadjuvant setting; this combination was administered to patients with locally advanced cervical adenocarcinoma., Methods: Eleven patients were treated with preoperative neoadjuvant chemotherapy. Those eligible included patients with previously untreated stage IB, II, or III adenocarcinoma with good performance status. Treatment consisted of bilateral internal iliac artery infusion of cisplatin (a total of 10 mg/day) for 30 min, followed by 5-FU (a total of 250 mg/day) given by 24-hour continuous infusion for 10 days. Treatment was repeated every 3 weeks for a total of two or three cycles. All except one patient with progressive disease underwent radical hysterectomy following neoadjuvant chemotherapy. Postoperative radiotherapy was given to the whole pelvis to 6 patients; 3 of the 6 patients with involved common iliac nodes received radiotherapy to a paraaortic field in addition to the whole pelvis., Results: Among 11 eligible patients, 7 had a partial response (64%). Stable disease was observed in 3 cases (27%) and progressive disease in 1 (9%). Histopathological changes related to chemotherapy, however, revealed only mild effects. Of the 24 treatment cycles administered, no Grade 3 or 4 toxicity was observed and there were no therapy-related deaths. The median follow-up period was 30 months (range, 1-65 months). The mean survival period was 34.7 months and the 5-year survival rate was 21.2%., Conclusions: Intraarterial neoadjuvant chemotherapy effectively reduced tumor size in patients with locally advanced cervical adenocarcinoma; however, a survival advantage was not clear., (Copyright 2001 Academic Press.)

Objective: The goal of this study was to identify risk factors in patients with node-positive stage IB, IIA, and IIB cervical carcinoma after radical hysterectomy with pelvic lymph node dissection and postoperative irradiation., Methods: Two hundred forty-two patients with FIGO stage IB, IIA, and IIB cervical carcinoma underwent radical hysterectomy with pelvic lymph node dissection; pathological analysis of the surgical specimen showed positive lymph nodes in 59 patients. These 59 patients were further treated with postoperative radiotherapy. Eighteen patients were in stage IB, 4 in stage IIA, and 37 in stage IIB. Histological tumor type, tumor size, lymph-vascular space invasion, parametrium infiltration, number of positive nodes, and involvement of common iliac nodes were assessed for correlation with cancer recurrence., Results: When all these variables were assessed in the Cox proportional regression analysis, parametrium infiltration (P = 0. 0199) and number of positive nodes (two or more nodes) (P = 0.0483) revealed the factor correlating significantly with disease-specific survival. Based on these two factors, node-positive patients could be divided into low-risk (n = 11), intermediate-risk (n = 29), and high-risk (n = 19) groups. The 5-year disease-specific survival for the low-risk group was 100% which was significantly better than the 39.1% for the high-risk group (P = 0.0012)., Conclusion: For patients in the high-risk group, it may be worthwhile to consider new strategies to improve survival., (Copyright 2000 Academic Press.)

We analyzed the clinical features of 25 ovarian cancer patients who were associated with germ-line mutations of BRCA1 from four site-specific ovarian cancer families and seven breast-ovarian cancer families in Japan. The average age at diagnosis was 51.1 years (range, 38-77 years). Histological examination revealed 24 serous cyst adenocarcinomas in 25 patients. In 23 patients with clear clinical records, 3 patients had stage I disease, 17 had stage III disease, and 3 had stage IV disease. Thirteen patients with stage III disease who were treated with cisplatin-containing chemotherapy following tumor reduction surgery showed more favorable outcomes in both the survival rate and disease-free intervals, compared with age- and treatment course-matched controls (5-year survival rate, 0.786 versus 0.303; median disease-free interval, 91.43 versus 40.92 months; P < 0.05 for both, by logarithmic rank test). Our statistical model for the inheritance of susceptibility to ovarian cancer was derived from the analysis of 26 patients and 19 healthy carriers of 12 families. The expected lifetime risk of ovarian cancer is about 80% for women with mutations of BRCA1. These results suggest that the clinical outcome of ovarian cancer with germ-line mutations of BRCA1 appears to be more favorable than that with sporadic cases and that the disease penetrance among pedigrees with germ-line mutations of the BRCA1 gene is substantially high.

We analyzed the alteration of BRCA1 in DNA obtained from 83 individuals of 13 Japanese site-specific ovarian cancer families and 6 breast-ovarian cancer families. Six germline mutations were detected in 7 families, which consisted of 4 breast-ovarian cancer and 3 site-specific ovarian cancer families, by single-strand conformation polymorphism analysis, followed by direct sequence determination. The mutations included three frameshifts, two nonsense mutations, and one missense mutation causing loss of a zinc-binding motif. The frequency of loss of heterozygosity at the microsatellite markers on the BRCA1 gene was 57% (8 of 14 cases) in site-specific ovarian cancer families, and 100% (6 of 6 cases) in breast-ovarian cancer families. All tumors of the patients carrying a mutation of BRCA1 showed deletion of wild-type alleles, implicating BRCA1 as a tumor suppressor gene. These results suggest that germline mutations of the BRCA1 gene play an important role in the carcinogenesis of breast and/or ovarian cancer in a majority of breast-ovarian cancer families and in some site-specific ovarian cancer families.

Ovarian cancer is the most lethal kind of gynecological malignancy. Though combination therapy has improved, the prognosis is still poor. It is a risk factor to have a member affected with breast or ovarian cancer in one's family or to have been affected with these diseases. Genetic testing will more effectively enable earlier diagnosis and cure of such diseases. Including the selected results of familial ovarian cancers, we discuss the effectiveness and difficulty of genetic testing of BRCA1 in Japan.