松岡 歩

OBJECTIVE: Therapy-related myeloid neoplasms (t-MNs) are often fatal and arise as late complications of previous anticancer drug treatment. No single-center case series has examined t-MNs in epithelial ovarian cancer (EOC). METHODS: All patients with EOC treated at Chiba University Hospital between 2000 and 2021 were included. We retrospectively analyzed the characteristics, clinical course, and outcomes of patients who developed t-MNs. RESULTS: Among 895 cases with EOC, 814 cases were treated with anticancer drugs. The median follow-up period was 45 months (interquartile range, 27-81) months. Ten patients (1.2%) developed t-MNs (FIGO IIIA in one case, IIIC in three, IVA in one, and IVB in five). Nine patients were diagnosed with myelodysplastic syndrome and one with acute leukemia. One patient with myelodysplastic syndrome developed acute leukemia. The median time from the first chemotherapy administration to t-MN onset was 42 months (range, 21-94 months), with t-MN diagnoses resulting from pancytopenia in four cases, thrombocytopenia in three, and blast or abnormal cell morphology in four. The median number of previous treatment regimens was four (range, 1-7). Paclitaxel + carboplatin therapy was administered to all patients, gemcitabine and irinotecan combination therapy to nine, bevacizumab to eight, and olaparib to four. Six patients received chemotherapy for t-MN. All patients died (eight cancer-related deaths and two t-MN-related deaths). None of the patients was able to restart cancer treatment. The median survival time from t-MN onset was 4 months. CONCLUSIONS: Patients with EOC who developed t-MN were unable to restart cancer treatment and had a significantly worse prognosis.

Background: We evaluated whether the serum hormone levels are useful in the differential diagnosis of granulosa cell tumors (GCTs), regardless of menopausal status. Methods: Serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, estradiol, and progesterone were measured preoperatively in all patients (n = 471) who underwent surgery for ovarian tumors at Chiba University Hospital between 2009 and 2021. These were compared in two groups, a GCT group (n = 13) and a group with other histological types (non-GCT) (n = 458). Results: The GCT group had significantly lower serum LH and FSH (p = 0.03 and p < 0.001, respectively) and significantly higher testosterone, estradiol, and progesterone (p < 0.001, p < 0.001, and p = 0.045, respectively) than the non-GCT group. Multivariate analysis revealed that serum FSH and estradiol were significantly associated with GCT (FSH, odds ratio (OR) = 0.0046, 95% confidence interval (CI) = 0.0026–0.22, p = 0.004; estradiol, OR = 0.98, 95% CI = 0.96–0.998, p = 0.046). Receiver-operating characteristic curve analysis for GCTs showed that the area under the curve of serum FSH was 0.99, with a sensitivity of 100% and a specificity of 98%, when the cutoff level was set at 2.0 IU/L. Conclusions: Preoperative serum FSH level is an extremely useful marker for differentiating GCTs from all ovarian tumors.

BACKGROUND/AIM: The 2014 International Federation of Gynecology and Obstetrics (FIGO) classification subdivides patients with stage IIIA1 ovarian, fallopian tube, and peritoneal cancers by the greatest dimension of metastatic lymph node without supporting evidence. This study aimed to assess the validity of this subdivision. PATIENTS AND METHODS: A retrospective single-institution cohort study was performed in patients with ovarian, fallopian tube, or peritoneal cancer from 2009 to 2020. We compared outcomes between patients diagnosed with IIIA1(i) (metastasis ≤10 mm in the greatest dimension) and IIIA1(ii) (metastasis >10 mm in the greatest dimension). RESULTS: Of the 895 patients, 46 (5.1%) were classified as stage IIIA1, 20 as IIIA1(i), and 26 as IIIA1(ii). In stage IIIA1(ii), there were significantly more cases of serous carcinoma (p<0.001), and the number of positive nodes and lymph node ratio were significantly higher than those in stage IIIA1(i) (p=0.001, p=0.002). Five-year progression-free survival was 68.7% in patients with stage IIIA1(i) cancer and 58.1% in those with stage IIIA1(ii) (p=0.58). Five-year overall survival was 83.1% in patients with stage IIIA1(i) cancer and 80.2% in those with stage IIIA1(ii) (p=0.44). Among other patient characteristics and pathologic findings, there were no prognostic factors for patients with stage IIIA1 cancer. CONCLUSION: In this retrospective cohort study, further classification of FIGO stage IIIA1 cancer was not significantly associated with patient outcomes.

INTRODUCTION: The aim of the study was to evaluate the influence of estradiol-producing ovarian tumors, including surface epithelial-stromal tumors, on the cervical cytology of postmenopausal women. METHODS: This case-controlled study included 160 postmenopausal women who underwent a gynecological surgery between January 2009 and December 2016. The relationship between serum estradiol levels and the maturation index of cervical cytology was examined. Patients with ovarian tumors and a high estradiol level (≥28 pg/mL) constituted the estradiol-producing ovarian tumor group (30 women, including 23 with surface epithelial-stromal tumors). The maturation index of this group was compared with that of the control group (130 women with normal estradiol levels [<28 pg/mL] with either ovarian tumors or uterine tumors). RESULTS: For all patients, the serum estradiol levels were significantly correlated with the maturation index (p < 0.001, r = 0.65). The maturation index of the estradiol-producing ovarian tumor group was significantly higher than that of the control group (0.67 ± 0.21 vs. 0.075 ± 0.16, p < 0.001). The area under the receiver operating characteristic curve for the maturation index was 0.94. The best maturation index cut-off level for estradiol-producing ovarian tumors was 0.20. Using this cut-off, the sensitivity and specificity were 94% and 82%, respectively. CONCLUSION: Estradiol-producing ovarian tumors influence cervical epithelial maturation in postmenopausal women. An increased maturation index may trigger the early detection of asymptomatic ovarian tumors.

OBJECTIVE: This study aimed to evaluate the presence of pathological residual tumor (pRT) in each initial disseminated site after neoadjuvant chemotherapy (NACT) to assess the appropriate surgical margins during interval debulking surgery (IDS) for a favorable prognosis. METHODS: This prospective descriptive study included patients with stage IIIC-IV epithelial ovarian, fallopian tubal, and peritoneal cancer. One hundred eleven patients underwent diagnostic exploratory laparotomy, and their initial intra-abdominal dissemination statuses were recorded. Any tumor >1 cm in diameter found during the exploratory laparotomy was resected during IDS even if it was macroscopically invisible after NACT. The pRT rate after NACT and negative predictive value (NPV; probability that sites with macroscopically invisible tumors have no pRT) during IDS were assessed in each disseminated site. RESULTS: A median of 5 NACT cycles were performed. Sites with a high incidence of pRT and low NPV included the rectosigmoid colon (71.4%, 38.6%), transverse mesentery (70.3%, 50.0%), greater omentum (68.3%, 51.7%), right diaphragm (61.9%, 48.1%), paracolic gutters (61.1%, 50.0%), and vesicouterine pouch (56.6%, 50.0%). Organs/tissues with a high incidence of pRT featured a low NPV. The median progression-free survival and overall survival in this cohort were 27.7 and 71.9 months, respectively. CONCLUSION: Even if a disseminated site >1 cm in diameter before NACT is invisible during IDS, microscopic disease remains present within it. The appropriate surgical margins for IDS with a favorable prognosis could be secured by resecting a lesion of >1 cm before NACT even if it is invisible during IDS.

OBJECTIVE: We investigated the learning curve for a monodisciplinary surgical team consisting of gynecologic oncologists performing cytoreductive surgery for advanced ovarian cancer, involving high-complexity procedures with bowel resection and upper abdominal surgery. METHODS: We investigated 271 consecutive patients with ovarian, fallopian tube, and peritoneal carcinoma undergoing cytoreductive surgery for stage III/IV disease. All operations were performed by a team consisting of only gynecologic oncologists. Patients were classified into 2 groups depending on the surgical complexity score (a cumulative score based on complexity and number of procedures performed). Learning curves for patients with moderate (4-7, 63 patients) and high scores (8-18, 208 patients) were evaluated using cumulative sum (CUSUM) analysis of operative time, total blood loss, and perioperative complications. RESULTS: Operative time and total blood loss showed a learning curve. The CUSUM curve for operative time peaked at the 28th and 51st case in the moderate- and high-score groups, respectively. The CUSUM curve for total blood loss peaked at the 16th and 55th case in the moderate- and high-score groups, respectively. The CUSUM curve for complications (Clavien-Dindo ≥ IIIb) showed a downward slope after the 6th case in the high-score group and remained within the acceptable range throughout the study. CONCLUSION: Proficiency in performing high-complexity surgery was achieved after approximately 50 cases and this number is greater than the number of cases required to perform moderate-complexity surgery. Acceptable rates of severe perioperative complications were observed even during the initial learning period in cases of high-complexity surgery.

OBJECTIVE: This study was performed to examine the safety of bowel resection and upper abdominal surgery in patients with advanced ovarian cancer performed by gynecologic oncologists after training in a monodisciplinary surgical team. METHODS: We implemented a monodisciplinary surgical team consisting of specialized gynecologic oncologist for advanced ovarian cancer. In the initial learning period in 65 patients with International Federation of Gynecology and Obstetrics (FIGO) III/IV, a gynecologic oncologist who had a certification as a general surgeon trained 2 other gynecologic oncologists in bowel resection and upper abdominal surgery for 4 years. After the initial learning period, the trained gynecologic oncologists performed surgeries without the certificated general surgeon in 195 patients with FIGO III/IV. The surgical outcomes and perioperative complications during the 2 periods were evaluated. RESULTS: The rates of achieving no gross disease after cytoreductive surgery were 80.0% in the initial learning period and 83.6% in the post-learning period (p=0.560). The incidence of anastomotic leakage after rectosigmoid resection, symptomatic pleural effusion or pneumothorax after right diaphragm resection, and pancreatic fistula after splenectomy with distal pancreatectomy in the 2 periods were 2 of 34 (6.0%), 1 of 33 (3.0%), and 3 of 15 (20.0%) patients in the initial learning period, and 12 of 147 (8.2%), 1 of 118 (0.8%), and 11 of 84 (13.1%) patients in the post-learning period, respectively. There were no significant differences between the 2 groups (p=0.270, p=0.440, p=0.520, respectively). CONCLUSION: Bowel resection and upper abdominal surgery can be performed safely by gynecologic oncologists.

Objective: Double inferior vena cava (IVC) is present in 1.0%–3.0% of the general population and can create clinical problems [1,2]. This anomaly is classified according to the presence and pattern of an interiliac vein; 23% of double-IVC cases do not have an interiliac vein, and variations exist in those with one [3]. Fewreports on retroperitoneal lymphadenectomy in patients with a double IVC exist. Herein, we show retroperitoneal lymphadenectomies in two patients with different double IVC classifications. Methods: We performed an interval debulking surgery, including retroperitoneal lymphadenectomy, in two cases of advanced ovarian cancer with double IVC. The retroperitoneal lymphadenectomy procedure was the same as that for patients with normal IVC. Case 1 involved a 53-year-old female having a double IVC without an interiliac vein. Case 2 involved a 51-year-old female having a double IVC with an interiliac vein from the right common iliac vein to the left IVC. Preoperative enhanced computed tomography revealed double IVC flow pattern in both cases; however, the presence of the interiliac vein in case 2 remained unrecognized. Results: Lymphadenectomy in case 1 was without complications. In case 2, major bleeding from the interiliac vein occurred during lymphatic tissue removal from the front of the sacral region. The bleeding was difficult to stop, and was finally stopped using Tacho Sil®. We then completed lymphadenectomy. Conclusions: During retroperitoneal lymphadenectomy in patients with a double IVC, it is important to determine the presence of an interiliac vein. Furthermore, its flow pattern should be considered with care.

OBJECTIVE: We evaluated the efficacy and safety of aggressive surgery for advanced ovarian cancer at a non-high-volume center. MATERIALS AND METHODS: We evaluated consecutive patients with stage III/IV ovarian, fallopian, and peritoneal cancer undergoing elective aggressive surgery from January 2008 to December 2012, which encompassed the first 5years after implementing an aggressive surgery protocol. After receiving appropriate training for 9months, a gynecological surgical team began performing multi-visceral resections. Primary debulking surgery was chosen when the team considered that optimal surgery was achievable on the initial laparotomy, otherwise interval debulking surgery was chosen (the protocol treatments). Analysis was performed on an intention-to-treat basis (full-set analysis), and outcomes were compared to those of patients who underwent standard surgery between 2000 and 2007. RESULTS: Of 106 consecutive patients studied, 87 (82%) underwent aggressive surgery per protocol and 19 were excluded. Serous carcinoma was the most common disease (78%), followed by clear cell carcinoma (7%), and 32% of the patients had stage IV disease. The respective median progression-free and overall survival rates increased from 14.6 and 38.1months before implementation, respectively, to 25.0 and 68.5months after implementation, respectively. Complete resection was achieved in 83 of the 106 patients (78%), and the surgical complexity score was high (>8) in 61 patients (58%); although there was no mortality within 12weeks of surgery, major complications occurred in 8 patients. CONCLUSIONS: We confirmed that outcomes improved after implementing aggressive surgery for advanced ovarian cancer, without causing a significant increase in mortality. Factors enhancing survival outcomes are discussed.

OBJECTIVE: The aim of the study was to evaluate the association between tumor histology and serum sex hormone levels in postmenopausal women with ovarian tumors. METHODS: We preoperatively measured serum levels of gonadotropins and sex steroids, including estradiol, progesterone, and testosterone, in 69 postmenopausal women who underwent surgical resection for ovarian tumors. Tumors were classified as surface epithelial-stromal tumors, sex cord-stromal tumors, germ cell tumors, and metastatic tumors. Surface epithelial-stromal tumors were divided into mucinous, serous, clear cell, and endometrioid tumor subgroups. Patients were divided into two groups depending on tumor type: mucinous and nonmucinous, and any association between these tumor types and serum sex hormone levels were evaluated. RESULTS: Univariate analyses revealed that serum sex steroid levels were significantly higher in women with mucinous ovarian tumors compared with women with other tumor types. Serum gonadotropin levels, age, body mass index, tumor size, and tumor malignancy status did not affect the sex steroid levels. Multivariate analysis evaluating sex steroid levels and tumor histology revealed that high serum progesterone levels were significantly and independently associated with mucinous ovarian tumors. A serum progesterone cut-off level of at least 1.3 nmol/L was the most accurate for differentiating mucinous tumors from other tumor types (area under the curve, 0.81; sensitivity, 75%; and specificity, 86%). CONCLUSIONS: Serum progesterone levels were significantly elevated in postmenopausal women with mucinous ovarian tumors. In these women, serum progesterone levels may thus represent a useful biomarker for predicting tumor histology preoperatively, which would aid treatment planning.