A Case of Cervical Squamous Cell Carcinoma Developing 33 Years After Conization.

We report a fatal case of early postoperative peritoneal dissemination in a patient who was diagnosed with cervical squamous cell carcinoma after laparoscopic hysterectomy for hematometra. A 73-year-old multiparous woman with pyometra and lower abdominal pain was referred to our hospital. Her medical history was remarkable for four open surgeries and conization at the age of 40 years. The cytology obtained from the mucosa of the palpated cervix was negative. The cytology and bacterial culture of the mucus collected from the uterine cavity were negative. Increasing fluid accumulation in the uterine cavity started to cause severe abdominal pain. A laparoscopy was performed. The small intestine showed extensive adhesions to the abdominal wall, which were dissected. A total hysterectomy was performed, and the uterus was placed in a collection bag, cut inside the bag, and retrieved transvaginally. Histopathological examination revealed nests of squamous cell carcinoma that replaced the entire uterine myometrium, and the tumor cells showed diffuse positivity for p16 on immunostaining. The patient was diagnosed with squamous cell carcinoma of the uterine cervix with invasion of the uterine myometrium. Three months later, the patient suffered from small bowel obstruction. A laparotomy was performed, and it revealed numerous disseminated lesions in the pelvic peritoneum and mesentery of the small intestine. Bypass surgery was performed. A biopsy of a disseminated lesion near the vaginal cuff revealed squamous cell carcinoma. The patient died within three weeks of bypass surgery.

Subcutaneous emphysema associated with laparoscopic or robotic abdominal surgery: a retrospective single-center study.

BACKGROUND: Subcutaneous emphysema (SCE) is a common complication in laparoscopic surgery. However, its precise incidence and impact on the clinical course are partially known. In this study, the incidence and risk factors of SCE were retrospectively analyzed. METHODS: Patients who underwent laparoscopic/robotic abdominal surgery (e.g., gastrointestinal, hepatobiliary, gynecologic, and urologic surgery) between October 2019 and September 2022 were retrospectively analyzed. The presence of SCE was confirmed by either conclusive findings obtained through chest/abdominal X-ray examination immediately after operation, or intraoperative palpation conducted by nurses. X-ray examination was performed in the operation room before extubation. RESULTS: A total of 2503 patients treated with laparoscopic/robotic abdominal surgery between October 2019 and September 2022 were identified and all of them were included in the analysis. SCE was confirmed in 23.1% of the patients (i.e., 577/2503). SCE was identified by X-ray examination in 97.6% of the patients. Extubation failure was observed in 10 patients; however, pneumothorax was not observed. Female sex (odds ratio [OR]: 2.09; 95% confidence interval [95%CI]: 1.69-2.57), age ≥ 80 years (OR 1.63; 95%CI 1.19-2.22), body mass index < 20 (OR 1.32; 95%CI 1.06-1.65), operation time > 360 min (OR 1.97; 95%CI 1.53-2.54), robotic surgery (OR 2.54; 95%CI 1.91-3.38), maximum intraabdominal pressure with CO2 > 15 mmHg (OR 1.79; 95%CI 1.02-3.16), and endo-tidal CO2 > 50 mmHg (OR 1.32; 95%CI 1.08-1.62)were identified as independent factors of SCE. Regarding the extubation failure due to SCE, age (OR 5.84; 95%CI 1.27-26.8) and maximum intraabdominal pressure with CO2 (OR 21.7; 95%CI 4.76-99.3) were identified as risk factors. CONCLUSION: Although the presence of SCE is associated with a low risk of severe complications, monitoring of the perioperative intraabdominal pressure is essential for performing safe laparoscopic/robotic surgery, particularly in elderly patients.

Weight-Loss Interventions and Levonorgestrel Intrauterine System Implantation for Early-Stage Endometrial Cancer and Atypical Endometrial Hyperplasia to Reduce Perioperative Risk of Severely Obese Patients.

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.

Fertility-sparing management of stage IIIC serous borderline ovarian tumor: A case report of a 20-year follow-up.

Multimodal treatment, including assisted reproductive technology, is necessary in young patients with advanced borderline ovarian tumors. However, the details of long-term follow-up cases have not been reported. In this report, a 19-year-old patient presented with a stage IIIC serous borderline tumor. The patient underwent five fertility-sparing surgeries. The tumor did not respond to any of the three lines of chemotherapy administered. Serological and radiological responses were observed following hormonal treatment with leuprorelin, followed by a fourth surgery. Before the planned fifth surgery for complete resection of both adnexa, cryopreservation of the fertilized eggs was performed. At age 36, when the disease-free interval exceeded the previous one, we proposed embryo transfer; however, she declined fertility treatment. The patient had developed rheumatoid arthritis and childbirth not a priority. The patient had lived without any evidence of disease for 7 years following the last surgery and 20 years after the initial visit.

Medroxyprogesterone as the Initial Systemic Treatment of Recurrent Endometrial Cancer: A Single Institutional Study.

BACKGROUND/AIM: Hormonal treatment is the preferred initial systemic therapy for patients with advanced or recurrent G1 or G2 endometrial cancer (EC) in terms of efficacy, toxicity, and economy. Few reports are available on the topic and we, therefore, conducted a retrospective study. PATIENTS AND METHODS: Patients with EC who received high-dose medroxyprogesterone (MPA) at our Hospital between January 2010 and December 2022 were reviewed. Patients who were treated for fertility preservation or had a history of systemic chemotherapy other than adjuvant therapy were excluded. RESULTS: Sixteen patients who were eligible for study inclusion had recurrent G1 or G2 EC. Their median age was 65 years (range=51-82 years), median body mass index was 22.6 kg/m2 (range=15.3-43.2 kg/m2), and all patients had an ECOG Performance Status of 0. All patients received 200 mg/day of MPA, and eight patients concomitantly received 100 mg/day of aspirin. None of the patients experienced severe adverse events. One patient had grade 2 deep vein thrombosis. Two patients discontinued MPA treatment because of adverse events. The response rate was 44% [95% confidence interval (CI)=20-68%] and median progression-free survival (PFS) was 6.9 months (95% CI=7.5-26 months). Four of 16 patients had PFS longer than 12 months, all of whom had positive tissue estrogen receptor (ER) and progesterone receptor (PR), and PFS at 2 years was 35% (95% CI=10.2-59.8%). CONCLUSION: Hormone therapy is effective long-term in ER- and PR-positive EC and can be recommended as initial systemic therapy. Toxicity is mild and manageable.

Comprehensive Genomic Profiling Detects Hereditary Cancers and Confers Survival Advantage in Patients With Gynaecological Cancers.

BACKGROUND/AIM: The clinical benefits of comprehensive genomic profiling (CGP) of tumours in patients with gynaecological cancers remain unknown. We investigated the utility of CGP in assessing patient survival and its efficacy in detecting hereditary cancers in gynaecological patients. PATIENTS AND METHODS: We retrospectively analysed the medical records of 104 gynaecological patients who underwent CGP between August 2018 and December 2022. The detection of actionable and accessible genomic alterations and administration of targeted therapy, as recommended by the molecular tumour board (MTB), were assessed. The overall survival (after second-line treatment in cervical and endometrial carcinomas and after platinum-resistant recurrence in ovarian carcinoma) was compared between patients with or without administration of MTB-recommended genotype-matched therapy. Germline findings were assessed using a variant allele frequency-tumour content graph. RESULTS: Among 104 patients, actionable and accessible genomic alterations were observed in 53 patients. Matched therapy was applied in 21 patients, comprising administration of repurposing itraconazole (n=7), immune checkpoint inhibitors (n=7), poly (ADP-ribose) polymerase inhibitors (n=5), and others (n=2). The median overall survival of patients receiving and not receiving matched therapy were 19.3 months and 11.2 months, respectively (p=0.036, hazard ratio=0.48). Among 12 patients with hereditary cancers, 11 patients were previously undiagnosed. Seven patients had hereditary breast and ovarian cancer, and five had other cancer. CONCLUSION: The implementation of CGP testing prolonged overall survival in gynaecological cancer as well as provided an opportunity for genetic counselling for newly-diagnosed patients with hereditary cancers and their families.

Itraconazole Modulates Phospholipid Levels in Tumor-associated Macrophages.

BACKGROUND/AIM: Itraconazole, an antifungal drug, repolarizes pro-tumorigenic M2 tumor-associated macrophages to anti-tumorigenic M1-like phenotypes, thereby inhibiting the proliferation of cancer cells; however, the underlying mechanism remains unclear. Therefore, we investigated the effect of itraconazole on membrane-associated lipids in tumor-associated macrophages (TAM). MATERIALS AND METHODS: M1 and M2 macrophages were derived from the human monocyte leukemia cell line (THP-1) and cultured with or without 10 µM itraconazole. Cells were homogenized and subjected to liquid chromatography/mass spectrometry (LC/MS) analysis to estimate the glycerophospholipid levels in the cells. RESULTS: Lipidomic analysis results, displayed on a volcano plot, revealed that itraconazole-induced altered phospholipid composition, with more pronounced changes in M2 macrophages than in M1. Notably, itraconazole significantly increased intracellular phosphatidylinositol and lysophosphatidylcholine levels in M2 macrophages. CONCLUSION: Itraconazole modulates the lipid metabolism of TAMs, which could have implications for the development of novel cancer therapies.

Phase II study of gemcitabine, cisplatin, and bevacizumab for first recurrent and refractory ovarian clear cell carcinoma Kansai Clinical Oncology Group-G1601.

Patients with advanced ovarian clear cell carcinoma (CCC) have a poor prognosis in the absence of an effective standard treatment. Combination therapy with gemcitabine, cisplatin, and bevacizumab (GPBev) is promising for ovarian CCC. Thus, we conducted a multi-institutional, phase II trial in Japan to examine the efficacy and safety of GPBev for CCC. This is the first study on the use of GPBev for CCC. Eighteen patients (median age, 56.5 years) with pathologically confirmed first recurrent or refractory CCC and having evaluable regions, as assessed using RECIST, were recruited between January 2017 and May 2019. Gemcitabine (1000 mg/m 2 ), cisplatin (40 mg/m 2 ), and bevacizumab (10 mg/kg) were administered intravenously on days 1 and 15, every 28 days, for 6-10 cycles, until disease progression or intolerable toxicity. The primary endpoint was overall response rate (ORR). The secondary endpoints included disease control rate (DCR) and adverse events (AEs). Fifteen patients (83.3%) completed 6-10 cycles of treatment; three patients (two with AEs and one with progressive disease) did not. The ORR was 61.1% [complete response (CR) 3 and partial response (PR) 8] and DCR was 88.9% (CR 3, PR 8, and stable disease 5). Grade 3 and 4 hematological AEs were observed in 16.7 and 5.6% of the patients, respectively. Nonhematological AEs of grades 3 and 4 were observed in 27.8 and 5.6% of the patients, respectively. GPBev is a promising therapy for CCC owing to the high ORR and acceptable toxicity for the first recurrence and refractory CCC.

Combination therapy of oral cyclophosphamide and bevacizumab for patients with recurrent ovarian and peritoneal cancer.

Chemotherapy for patients with recurrent cancer aims to obtain survival benefits, relieve symptoms, and improve quality of life. We used oral cyclophosphamide and bevacizumab (BEV) combination therapy in recurrent ovarian and peritoneal cancer cases, where standard chemotherapy was infeasible. Subsequently, we evaluated the safety and efficacy of this treatment. Between August 2014 and June 2020, patients received the following regimen: oral cyclophosphamide 50 mg daily and intravenous cyclic BEV 15 mg/kg every 3 weeks. Data from 2 facilities were retrospectively analyzed. Twenty-two patients were enrolled (20 with ovarian cancer and two with peritoneal cancer). The median follow-up period and age were 18.9 months (range, 5.0-51.5) and 60 years (range 37-81), respectively. Sixteen patients had platinum resistance. The median number of previous chemotherapy regimens was 2.5 (range 0-5). The median implementation cycle was five (range 2-14). Eighteen patients discontinued treatment due to side effects (3 patient) and disease progression (15 patient). Grade 2 toxicities included neutropenia (1 patient), proteinuria (1 patient), hypertension (2 patient), and esophagitis (1 patient). Two patients had complete response and one had a partial response. Five patients had stable disease. The response rate in platinum-sensitive recurrence was 33.3%, and 7.1% in platinum-resistant recurrence, and a clinical benefit was found in 8 (36.3%) patients. The median PFS and overall survival from cyclophosphamide and BEV initiation was 5.3 months (range, 0.8-23.5) and 9.2 months (range, 4.8-51.5), respectively. The combination of oral cyclophosphamide and BEV does not have a high response rate, but is well-tolerated and can be used safely in patients who are difficult to treat after second-line chemotherapy. Data from 2 facilities were retrospectively analyzed.

Extraskeletal Myxoid Chondrosarcoma of the Vulva: A Case Report.

Extraskeletal myxoid chondrosarcoma (EMC) of the vulva is extremely rare. We report our experience with a case of disease control by radiation therapy to a localized lesion of EMC. A 41-year-old woman presented to our clinic with a vulvar mass. Magnetic resonance imaging showed a 15 cm mass between the perineum and the medial thigh muscle. It was the "adductor magnus muscle." After the needle biopsy, a histopathological diagnosis of EMC was made. Tissue genomic analysis detected the EWSR1-NR4A3 fusion gene. A joint operation by the Department of Orthopedics, Gynecology, and Plastic Surgery was performed, which included a wide excision of the perineum, partial excision of the medial thigh muscle, and rectus abdominis valvuloplasty. Intraoperatively, pubic infiltration was detected. Postoperative pelvic radiotherapy was administered as adjuvant therapy. Recurrent common iliac lymph node metastases outside the irradiation field and multiple lung metastases were observed. Pazopanib was administered as adjuvant therapy. Pulmonary metastases were controlled, but the pelvic tumor had spread, so the patient underwent radiation therapy. After second-line chemotherapy with doxorubicin, left pleural effusion and mediastinal lymph node metastasis appeared, and third-line chemotherapy with eribulin mesylate was administered. The pleural effusion improved, but the patient developed cough again, and trabectedin was administered as the fourth chemotherapy. In this case, there was no local recurrence for three years after radiotherapy, suggesting the effectiveness of radiotherapy in local control.

Itraconazole Repolarizes Tumor-associated Macrophages and Suppresses Cervical Cancer Cell Growth.

BACKGROUND/AIM: Itraconazole (ITZ), an antifungal agent, has been reported to have anti-tumor effects in patients with multiple cancer types. We investigated the involvement of tumor-associated macrophages (TAMs) in its tumor-agnostic mechanism. MATERIALS AND METHODS: M1 and M2 macrophages were established from human monocyte leukemia cell line (THP-1) and their phenotypes were determined morphologically. Cell membrane antigens and secreted proteins were evaluated by western blots and enzyme-linked immunosorbent assay, respectively. The proteomic profiling of cells was done by liquid chromatography with tandem mass spectrometry and analyzed. Viability of cervical cancer cells (CaSki) was evaluated after addition of the supernatant of M2 macrophages and during co-culture with M2 macrophages, with or without 10-5 M ITZ. RESULTS: Co-culture of M1 macrophages inhibited the proliferation of CaSki cells (p=0.012), while that of M2 macrophages promoted their proliferation (p<0.0001). After treatment of M2 macrophages with ITZ for 24 h, they changed into M1-like shape with decreased expression of cluster of differentiation 163 (CD163) and chemokine ligand 18 (CCL18). The M1-like shape was maintained for 7 weeks of ITZ treatment and reverted to original after ITZ removal. Proteomic analysis of ITZ treated-M2 macrophages also demonstrated M1-like signature including the elevated levels of tumor necrosis factor (TNF)-related proteins. After treatment with ITZ, both the supernatant of the M2 macrophages and the co-culture with M2 macrophages significantly inhibited the proliferation of CaSki cells (each, p<0.0001). CONCLUSION: ITZ repolarized M2 macrophages to M1 type and suppressed cervical cancer cell growth demonstrating TAM-mediated anti-cancer activity of ITZ.

First-Line Gemcitabine, Nab-Paclitaxel, and Oxaliplatin Chemotherapy With Itraconazole in Patients With Metastatic Pancreatic Cancer: A Single Institution Experience.

BACKGROUND/AIM: Combination chemotherapy with gemcitabine, nab-paclitaxel, oxaliplatin, and itraconazole (GnPO-ITC) was administered as first-line chemotherapy in patients with metastatic pancreatic cancer (mPC). The efficacy and toxicity of these treatments were retrospectively investigated. PATIENTS AND METHODS: A total of 81 patients (mean age=64 years) with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 were enrolled in the study, and administered nab-paclitaxel (125 mg/m2), gemcitabine (1,000 mg/m2), and oxaliplatin (85 mg/m2) on day 1 and itraconazole (400 mg) on days -2 to +2, repeated every 2 weeks. RESULTS: Metastatic sites observed in patients included the liver (n=55, 68%), peritoneum (n=23, 28%), distant lymph nodes (n=24, 30%), and lungs (n=18, 22%). Within 28 days after initiation of chemotherapy, 15 patients (19%) experienced common ≥3 grade hematological adverse events. The major reason for discontinuation of treatment among the responders was peripheral sensory neuropathy in 36 patients (44%). The overall response rate to treatment was 64% [95% confidence interval (CI)=54-75%]. The median progression-free survival and median overall survival were 8.3 months (95% CI=6.8-9.8 months) and 14.4 months (95% CI=11.4-17.3 months), respectively. Among the 52 responders, 24 (46%) underwent conversion surgery, which did not improve survival (p=0.279). Second-line treatment with irinotecan was required in 71 (88%) patients. Hepatic arterial chemotherapy and radiotherapy were administered to 33 (41%) and 27 (33%) patients, respectively. CONCLUSION: The GnPO-ITC regimen showed promising efficacy with manageable toxicities for controlling disease progression and improving overall survival.

Metronomic chemotherapy using oral cyclophosphamide and bevacizumab for recurrent cervical cancer: A multi-institutional retrospective study.

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.

Clinical practice guideline for the treatment of malignant ascites: section summary in Clinical Practice Guideline for peritoneal dissemination (2021).

Patients with peritoneal dissemination (PD) caused by abdominal malignancies are often associated with massive ascites, which shows extremely dismal prognosis because of the discontinuation of systemic chemotherapy mostly due to poor performance status. Many treatment methods, such as simple drainage, peritoneovenous shunting (PVS) and cell-free and concentrated reinfusion therapy (CART), have been used for symptom relief. However, the clinical efficacies of these methods have not been fully investigated yet. Recently, we developed the Clinical Practice Guideline for PD caused by various malignancies according to "Minds Clinical Practice Guideline Development Guide 2017". In this guideline, we systematically reviewed information on clinical diagnosis and treatments for PD using PubMed databases (2000 - 2020), and clarified the degree of recommendation for clinical questions (CQ). The evidence level was divided into groups by study design and quality. The literature level and a body of evidence were evaluated in reference to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. Based on the results of systematic review, the strength of the recommendations was evaluated at a consensus meeting of the Guideline Committee. This is the English synopsis of the part of treatment of malignant ascites in Clinical Practice Guideline for PD, 2021 in Japanese. The guidelines summarize the general aspect of the treatment of malignant ascites and statements with recommendation strengths, evidence levels, agreement rates and future perspective for four raised clinical questions.

Itraconazole Inhibits Intracellular Cholesterol Trafficking and Decreases Phosphatidylserine Level in Cervical Cancer Cells.

BACKGROUND/AIM: Itraconazole shows anticancer activity in various types of cancer but its underlying mechanism is unclear. We investigated the effect of itraconazole on membrane-associated lipids. MATERIALS AND METHODS: To investigate the influences of itraconazole on cholesterol trafficking, cervical cancer CaSki cells were cultured with itraconazole and analyzed by Filipin staining followed by confocal microscopy. Effect on the glycerophospholipid profiles was analyzed by liquid chromatography/mass spectrometry (LC/MS). RESULTS: After itraconazole treatment, Filipin staining revealed cholesterol accumulation in the intracellular compartments, which was similar to the distribution after treatment of U18666A (cholesterol transport inhibitor). LC/MS analysis showed a significant decrease in phosphatidylserine levels and an increase in lysophosphatidylcholine levels in CaSki cells. CONCLUSION: Itraconazole inhibited cholesterol trafficking and altered the phospholipid composition. Alterations in the cell membrane can potentiate the anticancer activity of itraconazole.

Itraconazole Increases Resolvin E3 Concentration and 12/15-lipoxygenase Inhibitor Attenuates Itraconazole Cytotoxicity in Cervical Cancer Cells.

BACKGROUND/AIM: The anticancer mechanism of itraconazole remains unsolved; therefore, we studied itraconazole-induced alterations in specialized pro-resolving mediators (SPMs) in cancer cells. MATERIALS AND METHODS: The human cervical squamous carcinoma cell line CaSki was cultured with or without 1 µM itraconazole. Liquid chromatography/mass spectrometry analysis was conducted to identify SPMs that were influenced by itraconazole. Cell growth experiments were conducted using itraconazole and inhibitors targeting the metabolic pathways of candidate SPMs. RESULTS: Resolvin E3, resolvin E2, prostaglandin J2 (PGJ2), delta-12-PGJ2, and maresin 2 were identified as candidate SPMs. The 12/15-lipoxygenase inhibitor, which is involved in the conversion of 18-hydroxy-eicosapentaenoic acid to resolvin E3, attenuated the inhibitory effect of itraconazole. Inhibition of the PGJ2 metabolic pathway did not interfere with itraconazole treatment. CONCLUSION: The metabolic pathway of SPMs, including resolving E3, could be proposed as an anticancer target of itraconazole.

Successful Embolization of Collaterals from the Round Ligament Artery during Uterine Artery Embolization for Traumatic Uterine Leiomyoma Rupture: A Case Report.

We describe the case of a 48-year-old woman who presented with traumatic rupture of a giant leiomyoma and massive hemoperitoneum caused by slipping and falling in the bathroom. She was in shock on arrival, and resuscitation was performed. Contrast-enhanced computed tomography showed massive intra-abdominal hematoma and extravasation from the subserous leiomyoma. Uterine artery embolization was performed, but she went into shock again after 6 h. The second contrast-enhanced computed tomography revealed persistence of extravasation. During 2nd UAE, an angiogram revealed extravasation originating from left round ligament artery. After the embolization of the left round ligament and bilateral uterine arteries, the patient recovered from shock. Total abdominal hysterectomy was performed on day 2 of admission to prevent re-bleeding and infection, then she discharged on day 19 of admission.

Recurrent uterine serous carcinoma with a germline pathogenic BRCA2 variant treated using olaparib: A case report.

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.

S-1, Oxaliplatin, Nab-paclitaxel and Itraconazole for Conversion Surgery for Advanced or Recurrent Gastric Cancer.

AIM: To evaluate the efficacy of chemotherapy with itraconazole for advanced or recurrent gastric cancer. PATIENTS AND METHODS: Patients with human epidermal growth factor receptor 2 (HER2) negative unresectable gastric cancer referred to our hospital were included. The regimen comprised 160 mg/m2 nab-paclitaxel i.v. and 100 mg/m2 oxaliplatin i.v. on day 1, 60 mg/m2 S-1 orally on days 1-3, and 400 mg itraconazole orally on days -2 to 2, repeated every 2 weeks for 6-8 cycles. RESULTS: Twenty-three patients aged 40-80 years (median age=68 years) were enrolled, of whom 21 had stomach cancer and two gastroesophageal junction cancer. Regarding stage, two, one, and 20 patients had stage IIIA, IIIB, and IV, respectively. Among patients with liver metastases, 2/10 had simultaneous lung metastases. Nine patients had peritoneal dissemination, and five patients with stage IV disease developed recurrence after primary surgery followed by adjuvant S-1. The other 18 patients had no history of surgery or chemotherapy. The response rate was 70% (complete response in two; partial response in 14). Among 12 patients (67%) who underwent conversion surgery, R0 resection was conducted in eight, and no residual tumour was observed in two. For the population overall, the median overall survival was 24 months (95% confidence intervaI=21 months-not reached) and the 1-year overall survival rate was 95% (95% confidence intervaI=67-98%). Grade 3/4 neutropenia and grade 2 peripheral sensory neuropathy occurred in five (22%) and six (26%) patients, respectively, while no patient developed grade 3/4 thrombocytopenia. CONCLUSION: Chemotherapy with itraconazole is promising for patients with unresectable gastric cancer.

Challenges in Managing Patients with Hereditary Cancer at Gynecological Services.

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.