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Endometrial cancer (EC) and atypical endometrial hyperplasia (AEH) are associated with obesity, which increases the perioperative morbidity and surgical difficulties in laparoscopic and robotic surgery. Weight-loss interventions (WLIs) are likely to reduce morbidity; however, delayed surgery may cause cancer progression. To minimize the tumor progression, levonorgestrel intrauterine system (LNG-IUS) with minimal side effects was used until the planned surgery. During 2016 and 2021, we conducted preoperative management of WLI using LNG-IUS for seven highly obese women with a body mass index (BMI) ≥35 kg/m2 who had AEH and EC with Grade 1 and no myometrial invasion on magnetic resonance imaging. In three of the seven patients, the BMI decreased by more than 5. Two patients with AEH achieved remission after LNG-IUS placement and requested conservative management. Five patients with EC underwent laparoscopic hysterectomy, without perioperative complications.

No standard chemotherapy is available after disease progression or anaphylaxis during platinum chemotherapy among patients with recurrent cervical cancer. Here we report the efficacy and toxicities of metronomic chemotherapy consisting of 50 mg of oral cyclophosphamide (CPA) daily and intravenous 15 mg/kg of bevacizumab (BEV) repeated every 3 weeks (CPA-BEV). Treated patients were retrospectively reviewed. Adverse events and response rates were recorded according to the Common Toxicity Criteria for Adverse Events (CTCAE) ver 5.0 and Response Evaluation Criteria In Solid Tumors ver 1.1, respectively. Eleven patients had been treated with CPA-BEV between 2016 and 2021.The pathologic types were squamous cell carcinoma in seven patients, adenocarcinoma in three, and large cell neuroendocrine carcinoma in one. Nine patients had primary concurrent chemoradiotherapy (CCRT). Five patients received more than one prior chemotherapy (excluding CCRT). Six patients had progressive disease during prior platinum-based chemotherapy, four patients recurred within 6 months of the last platinum administration, and one patient had platinum anaphylaxis. Grade 3 or more hematologic toxicities and grade 2 or more non-hematological toxicities were observed in one with grade 3 neutropenia and in one with grade 2 proteinuria, respectively. The median duration of chemotherapy was 2.8 months (range 0.2–30.6 months). One patient had CR but none had PR. Median progression-free survival was 2.8 months (95 %CI: 2.1–10.7 months), and median overall survival was 13.6 months (95 %CI: 8.4–33.7 months). In conclusion, the CPA-BEV regimen showed favorable antitumor activity with minimal toxicity and is promising candidate for second-line chemotherapy.

A germline pathogenic variant in BRCA2 was secondarily found through genomic sequencing of uterine serous carcinoma. Clinical response to olaparib was observed in recurrent uterine serous carcinoma with a germline BRCA2 mutation. Here, we report, for the first time, a long-term clinical response to olaparib in a patient with uterine serous carcinoma and a germline pathogenic BRCA2 variant.

Abstract Background Primary malignant melanoma of the vagina is extremely rare, with a poorer prognosis than cutaneous malignant melanoma. Previous studies have explored the repurposing of itraconazole, a common oral anti-fungal agent, for the treatment of various cancers. Here, we describe a patient with metastatic, unresectable vaginal malignant melanoma treated with 200 mg oral itraconazole twice a day in a clinical window-of-opportunity trial. Case presentation A 64-year-old Japanese woman with vaginal and inguinal tumours was referred to our institution. On the basis of an initial diagnosis of vaginal cancer metastatic to the inguinal lymph nodes, we treated her with itraconazole in a clinical trial until the biopsy and imaging study results were obtained. During this period, biopsies were performed three times, and 18F-fluoro-deoxyglucose positron emission tomography (FDG/PET)–computed tomography (CT) was performed twice. Biopsy results confirmed the diagnosis of primary malignant melanoma of the vagina. Imaging studies revealed metastases to multiple sites, including the brain, for which she underwent gamma-knife radiosurgery. During the window period before nivolumab initiation, the patient received itraconazole for 30 days. Within a week of itraconazole initiation, pain in the inguinal nodes was ameliorated. PET–CT on days 6 and 30 showed a reduction in tumour size and FDG uptake, respectively. The biopsied specimens obtained on days 1, 13, and 30 were subjected to cDNA microarray analysis, which revealed a 100-fold downregulation in the transcription of four genes: STATH, EEF1A2, TTR, and CDH2. After 12 weeks of nivolumab administration, she developed progressive disease and grade 3 immune-related hepatitis. Discontinuation of nivolumab resulted in the occurrence of left pelvic and inguinal pain. Following re-challenge with itraconazole, the patient has not reported any pain for 4 months. Conclusion The findings of this case suggest that itraconazole is a potential effective treatment option for primary malignant melanoma of the vagina. Moreover, we identified potential itraconazole target genes, which could help elucidate the mechanism underlying this disease and potentially aid in the development of new therapeutic agents.

Standard chemotherapy for women with advanced or recurrent cervical cancer involves a combination of paclitaxel, platinum, and bevacizumab. However, for patients who experience anaphylaxis in response to paclitaxel or platinum, have permanent peripheral neuropathy, or develop early recurrence or progressive disease during first-line chemotherapy, the development of a non-taxane non-platinum regimen is mandatory. Clinical trials using anti-angiogenic treatment demonstrated favorable outcomes in cases of highly vascularized cervical cancer. Metronomic chemotherapy has been considered an anti-angiogenic treatment, although its use in combination with bevacizumab has not been studied in cervical cancer. We treated four patients with recurrent cervical cancer with 50 mg of oral cyclophosphamide daily and 15 mg/kg of intravenous bevacizumab every 3 weeks (CFA-BEV). One patient experienced disease progression after 4 months, whereas the other three patients continued the regimen until their last follow-up at 13, 14, and 15 months, respectively. One patient suffered from grade 3 neutropenia; however, no grade 2 or higher non-hematological toxicities were observed. These cases demonstrate the use of CFA-BEV with minimal toxicity and expected anti-cancer activity and indicate that this regimen should be considered for second-line chemotherapy in advanced recurrent cervical cancer. Keywords: Cervical cancer, Metronomic chemotherapy, Bevacizumab

Abstract Background This study aimed to evaluate the current status of secondary debulking surgery (SDS) and tertiary debulking surgery (TDS; performed for recurrence after SDS) and to assess the overall survival after recurrence of Müllerian epithelial cancer in Japan. We also evaluated the data of patients who underwent a fourth debulking surgery (i.e., quaternary debulking surgery (QDS)). Methods We conducted a retrospective study of 164 patients with recurrent Müllerian epithelial cancers (i.e., ovarian, tubal, and peritoneal cancers). The SDS was performed between January 2000 and September 2014 in 20 Japanese hospitals. Clinicopathological data were collected and analyzed. Results Of the 164 patients, 66 patients did not have a recurrence or died after SDS. Ninety-eight patients had a recurrence after SDS. Forty-three of the 98 patients underwent TDS; 55 of the 98 patients did not undergo TDS and were classified into the non-TDS group. The overall survival (OS) after SDS was significantly better in the TDS group than in the non-TDS group. The median OS after SDS was 123 and 42 months in the TDS group and non-TDS group, respectively. Of the 43 patients who received TDS, 11 patients were further treated with QDS. The median OS after SDS was 123 months for patients who underwent QDS. Conclusions This multicenter study on the prognosis of post-SDS is apparently the first report on QDS in Japan. Patients undergoing TDS have a good prognosis, compared to patients in the non-TDS group. Novel drugs are being evaluated; however, debulking surgery remains a necessary treatment for recurrence.

Ovarian Sertoli cell tumors (SCTs) are rare sex cord tumors (Oliva et al., 2005). The standard treatment for high-grade SCTs is surgery followed by platinum-based chemotherapy. Although platinum-based chemotherapy is also an option for recurrent SCTs (Sigismondi et al., 2012), there is no established chemotherapy regimen for platinum-resistant recurrent SCTs. The effectiveness of pazopanib in treating epithelial ovarian cancer has recently been reported (du Bois et al., 2014; Pignata et al., 2015). In the case described herein, pazopanib was used to treat the platinum-resistant recurrence of a high-grade Sertoli cell tumor, and the response was evaluated by 18F-fluoro-deoxyglucose positron emission tomography (FDG-PET)-computed tomography (CT). Written informed consent to reporting the case was obtained from the patient.

Aim. To reveal current problems and challenges faced by our gynecologic services department in managing patients with hereditary cancers. Methods. We collected clinical data of patients with hereditary cancers, identified via genetic testing (or clinically diagnosed in cases of Cowden syndrome or Peutz–Jeghers syndrome), and treated in our gynecological department from 2012 to 2018. Results. Fifteen patients had hereditary breast and ovarian cancer (HBOC), 6 had Lynch syndrome, 2 had Cowden syndrome, and 2 had Peutz–Jeghers syndrome. Five patients diagnosed with HBOC were younger than 40 years at diagnosis. Risk-reducing salpingo-oophorectomy (RRSO) was performed on 1 patient with a BRCA1 mutation at age 38 years. Seven patients overall underwent RRSO, and none had malignancies on pathological examinations. Peritoneal washing cytology (PWC) was suspicious for malignancy in one patient; however, subsequent PWC at 6 months after RRSO was negative. A patient with endometrial cancer and Lynch syndrome and a patient with atypical endometrial hyperplasia (AEH) and Cowden syndrome strongly desired fertility preservation. They achieved remission after medroxyprogesterone acetate treatment and multiple dilations and curettages, respectively. One patient with Lynch syndrome developed AEH after 11 years of surveillance. Laparotomy revealed adjacent low-grade and high-grade serous ovarian cancer with positive ascites cytology. She had no recurrence during 7-year follow-up after laparotomy. Conclusion. Managing patients with hereditary cancer, positive or false-positive ascites cytology discovered during RRSO, and desired preservation of fertility is highly challenging.

A 48-year-old woman underwent a total abdominal hysterectomy after preoperative diagnosis of multiple uterine leiomyomas. The histopathological diagnosis was leiomyosarcoma (LMS). After 47 months, multiple lung metastases were detected and resected. The patient was also diagnosed with pelvic bone metastasis and received six cycles of adjuvant chemotherapy with gemcitabine plus docetaxel and local radiation therapy to control the pain. Seventy-seven months from the initial diagnosis, she had a headache and developed left hemiparesis and aphasia. Imaging studies detected a solitary brain metastasis in the right frontal lobe. The patient underwent a craniotomy and resection of the lesion, which was a confirmed metastasis from uterine LMS by histopathology. One month after the craniotomy, the patient experienced lower abdominal pain, and a pelvic metastasis was detected. She was prescribed oral pazopanib (800 mg per day). For twelve months, she remained asymptomatic, but gradually, pelvic pain increased due to pelvic mass growth. After 14 months of pazopanib treatment, pazopanib was discontinued. To date, for 18 months after the brain surgery, she is alive with disease, and the brain metastasis has not recurred.

Itraconazole, a common anti-fungal agent, has demonstrated potential anticancer activity, including reversing chemoresistance mediated by P-glycoprotein, modulating the signal transduction pathways of Hedgehog, mechanistic target of rapamycin and Wnt/ß-catenin in cancer cells, inhibiting angiogenesis and lymphangiogenesis, and possibly interfering with cancer-stromal cell interactions. Clinical trials have suggested the clinical benefits of itraconazole monotherapy for prostate cancer and basal cell carcinoma, as well as the survival advantage of combination chemotherapy for relapsed non-small cell lung, ovarian, triple negative breast, pancreatic and biliary tract cancer. As drug repurposing is cost-effective and timesaving, a review was conducted of preclinical and clinical data focusing on the anticancer activity of itraconazole, and discusses the future directions for repurposing itraconazole as an anticancer agent. [ABSTRACT FROM AUTHOR]

Objectives: We conducted a retrospective multi-institutional study to evaluate the efficacy and toxicity of intraperitoneal or intrapleural triamcinolone acetonide (TA), a slowly metabolized corticosteroid administration for the management of malignant ascites or pleural effusion.Materials and Methods: The medical records of patients with gynecologic cancer who were treated with paracentesis or thoracocentesis followed by administration of 400 mg of TA between 2005 and 2014 were reviewed.Results: The median age of the 74 eligible patients was 59 years. An Eastern Cooperative Oncology Group performance status 3-4 was present in 53 patients (73%), and 52 patients (70%) had ovarian cancer. Paracentesis followed by TA administration was performed in 65 patients (88%), and 37 patients (50%) were treated in a palliative setting. Chemotherapy or surgery after TA administration was performed in 37 patients (50%) in an aggressive setting, of which 14 patients (19%) were treated at the primary phase and 23 patients (31%) were treated at recurrent phase. The time interval of serial drainage was prolonged in 15 of 19 assessable patients, resulting in a response rate of 79% (95% confidence interval [95% CI]: 54-94%). Median overall survival after TA therapy in a palliative setting was 36 days (95% CI: 19-58 days). After TA therapy in a palliative setting, one patient complained of mild abdominal pain, two patients with advanced peritonitis carcinomatosis experienced bowel perforation, and three patients died within 7 days owing to disease progression.Conclusions: Intraperitoneal and intrapleural TA administration were feasible and effective in symptomatic control of ascites and pleural effusion. [ABSTRACT FROM AUTHOR]