松岡 歩

OBJECTIVE: Splenectomy with or without distal pancreatectomy is occasionally performed during cytoreductive surgery for advanced ovarian cancer. We investigated pre-, intra-, postoperative risk factors and predictors of clinically relevant postoperative pancreatic fistula (CR-POPF) in patients who underwent cytoreductive surgery for advanced ovarian cancer. METHODS: We investigated 165 consecutive patients with ovarian, fallopian tube, and peritoneal carcinoma categorized as stage III/IV disease, who underwent splenectomy with or without distal pancreatectomy as a component of cytoreductive surgery performed as initial treatment at Chiba University Hospital. Patient characteristics, clinical factors, and surgical outcomes were compared between those with and without CR-POPF. RESULTS: CR-POPF occurred in 20 patients (12%). There were no significant intergroup differences in the characteristics between patients with CR-POPF and patients without CR-POPF except for operative time, intraoperative blood loss, amylase (AMY) levels in drain fluid on postoperative day (POD)1 and POD3, and pancreatic stump thickness. Multivariate analysis showed that the POD3 drain fluid AMY level was the only significant risk factor and predictor of CR-POPF in patients who underwent cytoreductive surgery for advanced ovarian cancer. The receiver operating characteristic curve of the POD3 drain fluid AMY level, which predicted development of CR-POPF showed an area under the curve of 0.77, and the optimal cut-off value of AMY was 808 U/L. A pancreatic fistula did not occur in patients with POD3 drain fluid AMY levels <130 U/L. CONCLUSION: The POD3 drain fluid AMY level can be early diagnostic predictor CR-POPF after splenectomy with or without distal pancreatectomy for advanced ovarian cancer.

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.

Extended colon resection is often performed in advanced ovarian cancer. Restoring intestinal continuity and avoiding stoma creation improve patients' quality of life postoperatively. We tried to minimize the number of anastomoses, restore intestinal continuity, and avoid stoma creation for 295 patients with stage III/IV ovarian cancer who underwent low anterior rectal resection (LAR) with or without colon resection during cytoreductive surgery. When the remaining colon could not reach the rectal stump after left hemicolectomy with LAR, we used the following techniques for tension-free anastomosis: right colonic transposition, retro-ileal anastomosis through an ileal mesenteric defect, or an additional colic artery division. Rates of stoma creation and rectal anastomotic were 3% (9/295) and 6.6% (19/286), respectively. Among 21 patients in whom the remaining colon did not reach the rectal stump after left hemicolectomy with LAR, 20 underwent tension-free anastomosis, including eight, six, and six patients undergoing right colonic transposition, retro-ileal anastomosis through an ileal mesenteric defect, and an additional colic artery division, respectively. Colorectal anastomosis is feasible for patients with extended colonic resection. Low anastomotic leakage and stoma rates can be achieved with careful attention to colonic mobilization and tension-free anastomosis.

(1) Background: We investigated survival outcomes following first-line chemotherapy before and after approval of bevacizumab (Bev) for ovarian cancer in Japan to evaluate the efficacy of Bev for advanced clear cell carcinoma (CCC). (2) Methods: We investigated 28 consecutive patients diagnosed with CCC (stages III/IV) at our hospital between 2008 and 2018. Bev was administered for treatment of advanced CCC after approval in Japan in November 2013. Progression-free survival (PFS) was compared between 10 patients treated before Bev approval (2008–2013, Bev- group) and 18 patients treated after Bev approval (2014–2018, Bev+ group) for first-line chemotherapy. (3) Results: No intergroup difference was observed in patient characteristics. The rate of completeness of resection was higher in the Bev − group (9/10, 90%) than in the Bev+ group (15/18, 83%) (p = 0.044). Eleven (61%) patients in the Bev + group received ≥ 21 cycles of Bev. The median PFS increased from 12.0 months before Bev approval to 29.8 months after Bev approval (Wilcoxon test, p = 0.026). Multivariate analysis showed that performance status (p = 0.049), Bev administration (p = 0.023) and completeness of resection (p = 0.023) were independent prognostic factors for PFS. (4) Conclusions: Bev incorporated into first-line chemotherapy might improve PFS in patients with advanced CCC. We hope that our findings will be confirmed in adequate clinical trials.

BACKGROUND: To investigate whether rectosigmoid colectomy can improve the prognosis of patients with early-stage ovarian cancer when the ovarian tumor adheres to the rectum. METHODS: We retrospectively studied 210 consecutive patients with stage I/II ovarian cancer treated between 2000 and 2016. The surgical strategy differed between the periods 2000-2007 and 2008-2016 with respect to adhesion between the ovarian tumor and rectum. In the former period, ovarian tumor was exfoliated from the rectum. Only when the residual tumor was apparently observed on the rectal surface after salpingo-oophorectomy with hysterectomy, it was subsequently removed by colorectal surgeons performing rectosigmoid colectomy. In the latter period, the ovarian tumor was resected en bloc with the rectum by performing rectosigmoid colectomy. We compared the progression-free survival (PFS) between the two treatment periods. RESULTS: Rectosigmoid colectomy was performed more frequently in the latter period than in the former period (43 patients, 31% vs. 6 patients, 8%, p < 0.001). There was no significant difference in complete resection rate between the two periods (97% in the former period, 99% in the latter period, p = 0.278). However, the 5-year PFS rate was significantly higher in the latter period than in the former period (86.0% vs. 74.4%, log-rank test, p = 0.034). Multivariate Cox proportional-hazards regression analysis indicated that disease stage (hazard ratio [HR], 2.87, 95% confidence interval [CI] 1.14-7.34) and treatment period (HR 0.32, 95% CI 0.14-0.73) were independent risk factors for recurrence. CONCLUSIONS: Rectosigmoid colectomy could improve the prognosis of patients with early-stage ovarian cancer when the ovarian tumor adheres to the rectum.

BACKGROUND: This study aimed to evaluate the safety and efficacy of weekly paclitaxel and cisplatin chemotherapy (wTP) in patients with ovarian cancer who developed carboplatin hypersensitivity reaction (HSR). METHODS: We retrospectively investigated 86 patients with ovarian, fallopian tube, and peritoneal carcinoma who developed carboplatin HSR during previous chemotherapy (carboplatin and paclitaxel) at our institution between 2011 and 2019. After premedication was administered, paclitaxel was administered over 1 h, followed by cisplatin over 1 h (paclitaxel 80 mg/m2; cisplatin 25 mg/m2; 1, 8, 15 day/4 weeks). We investigated the incidence of patients who successfully received wTP for at least one cycle, treatments compliance, progression-free survival (PFS), and overall survival (OS). RESULTS: The median number of wTP administration cycles was 4 (Interquartile Range IQR, 3-7), 71 patients (83%) successfully received wTP, and 15 patients (17%) developed cisplatin HSR. The efficacy of treatment was as follows: 55 (64%) patients completed the scheduled wTP, 9 (10%) patients discontinued due to HSR to cisplatin within 6 cycles, 1 (1%) patient discontinued due to renal toxicity (grade 2) at the 6th cycle, and 21 (24%) patients discontinued due to progressive disease within 6 cycles. The median PFS and OS after administration of wTP were 10.9 months (95% CI: 7.7-17.7) and 25.9 months (95% CI: 19.0-50.2), respectively. CONCLUSIONS: wTP was safe and well-tolerated in patients who developed carboplatin HSR.

OBJECTIVE: We investigated the efficacy and toxicity of tailored-dose chemotherapy with gemcitabine and irinotecan for platinum-refractory/resistant ovarian or primary peritoneal cancer. METHODS: We enrolled patients with ovarian or primary peritoneal cancer who received ≥2 previous chemotherapeutic regimens but developed progressive disease during platinum-based chemotherapy or within 6 months post-treatment. All patients received gemcitabine (500 mg/m²) and irinotecan (50 mg/m²) on days 1 and 8 every 21 days at the starting dose. The dose was increased or decreased by 4 levels in subsequent cycles based on hematological or non-hematological toxicities observed. The primary endpoint was progression-free survival (PFS), and secondary endpoints were disease control rate (DCR), overall survival (OS), and adverse events. RESULTS: We investigated 25 patients who received 267 cycles (median 8 cycles/patient) between October 2008 and May 2011. Tailored-dose gemcitabine was administered up to the 5th cycle as follows: 1,000 mg/m² in 1 (4%), 750 mg/m² in 16 (64%), 500 mg/m² in 6 (24%), and 250 mg/m² in 2 patients (8%). The median PFS and OS were 6.2 months (95% confidence interval [CI]=2.7-10.7) and 16.8 months (95% CI=9.4-30.7), respectively. The DCR was 76%, and PFS was >6 months in 12 of 25 patients (48%). Grade 3 hematological toxicities included leukopenia (9.4%), neutropenia (11.2%), anemia (9.8%), and thrombocytopenia (1.1%). Grade 3/4 non-hematological toxicities did not occur except for fatigue in one patient. CONCLUSIONS: Tailored-dose chemotherapy with gemcitabine and irinotecan was effective and well tolerated in patients with platinum-refractory/resistant ovarian or primary peritoneal cancer. TRIAL REGISTRATION: UMIN Clinical Trials Registry Identifier: UMIN000004449.

We examined whether the extent of initial peritoneal dissemination affected the prognosis of patients with advanced ovarian, fallopian tube, and peritoneal carcinoma when initially disseminated lesions > 1 cm in diameter were removed, regardless of the timing of aggressive cytoreductive surgery. The extent of peritoneal dissemination was assessed by the peritoneal cancer index (PCI) at initial laparotomy in 186 consecutive patients with stage IIIC/IV. Sixty patients underwent primary debulking surgery and 109 patients underwent neoadjuvant chemotherapy followed by interval debulking surgery. Seventeen patients could not undergo debulking surgery because of disease progression during neoadjuvant chemotherapy. The median initial PCI were 17. Upper abdominal surgery and bowel resection were performed in 149 (80%) and 171 patients (92%), respectively. Residual disease ≤ 1 cm after surgery was achieved in 164 patients (89%). The initial PCI was not significantly associated with progression-free survival (PFS; p = 0.13) and overall survival (OS; p = 0.09). No residual disease and a high-complexity surgery significantly prolonged PFS (p < 0.01 and p = 0.02, respectively) and OS (p < 0.01 and p ≤ 0.01, respectively). The extent of initial peritoneal dissemination did not affect the prognosis when initially disseminated lesions > 1 cm were resected.

BACKGROUND: This study investigated the pattern of first recurrence of advanced ovarian cancer before and after the introduction of aggressive surgery. METHODS: We investigated 291 patients with stage III/IV epithelial ovarian, fallopian tube, and peritoneal cancer. Aggressive surgery including gastrointestinal and upper abdominal surgeries was introduced for advanced ovarian cancer in 2008. The site and time until first recurrence were compared between 70 patients treated without aggressive surgery (2000-2007) and 221 patients who underwent aggressive surgery (2008-2016). RESULTS: The intraperitoneal recurrence rate was significantly lower in patients treated during 2008-2016 than in patients treated during 2000-2007 (55% [82/149] vs. 81% [46/57], p < 0.001). The median time to intraperitoneal recurrence was significantly longer during 2008-2016 than during 2000-2007 (36.2 months, 95% confidence interval [CI] 31.7-60.0 vs. 14.6 months, 95% CI 11.3-20.1, log-rank test: p < 0.001). However, extraperitoneal recurrence rate was significantly higher during 2008-2016 than during 2000-2007 (27% [40/149] vs. 2% [1/57], p < 0.001). Extraperitoneal recurrence occurred during 2008-2016 in the pleura/lungs and the para-aortic lymph nodes above the renal vessels. Cox proportional hazards regression analysis revealed that treatment period (HR 0.49, 95% CI 0.34-0.71, p < 0.001) and bevacizumab use (HR 0.58, 95% CI 0.39-0.87, p = 0.009) were independently associated with intraperitoneal recurrence; stage IV disease (HR 1.87, 95% CI 1.14-3.06, p = 0.034) was independently associated with extraperitoneal recurrence. CONCLUSION: Aggressive surgery reduced intraperitoneal recurrence and prolonged time to recurrence, contributing to better patient survival.

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: Metastatic lymph node resection around the porta hepatis is sometimes required to achieve complete cytoreduction for ovarian, fallopian tube, and primary peritoneal cancer. Hence, this study aimed to present the surgical approach of peripancreatic lymph node removal around the porta hepatis as part of primary debulking surgery. METHODS: A 75-year old woman with stage IIIC primary peritoneal serous carcinoma underwent primary debulking surgery by means of the following procedures: bilateral salpingo-oophorectomy, total hysterectomy, omentectomy, total pelvic peritonectomy, rectosigmoid colectomy with anastomosis, right hemicolectomy, right diaphragm resection, partial jejunal resection, and pelvic and para-aortic lymphadenectomy. Furthermore, she underwent enlarged peripancreatic lymph nodes resection located in the hepatoduodenal ligament and on the posterior pancreatic head. An anatomic variant of the common hepatic artery was identified to be arising from the superior mesenteric artery and not from the celiac artery. The common hepatic artery ran behind the portal vein. We resected the lymph nodes without causing injury of the hepatic artery, portal vein, and common bile duct and achieved complete cytoreduction. RESULTS: The histological examination revealed high-grade serous carcinoma in three of nine resected peripancreatic lymph nodes. In contrast, only one lymph node metastasized in the interaortocaval region among the 63 resected regional lymph nodes (paraaortic and pelvic lymph nodes). CONCLUSION: Metastatic peripancreatic lymph nodes resection around the porta hepatis is feasible and sometimes necessary for cytoreductive surgery for advanced ovarian, fallopian tube, and primary peritoneal cancer.

The signs of granulosa cell tumors（GCTs）arising from the ovary depend on the types of hormones produced by the tumor. Estrogens cause continuous uterine bleeding, whereas inhibins are responsible for amenorrhea. We describe an unusual case of GCT in which the tumor-related manifestations changed over 9 years, from initial secondary amenorrhea to continuous uterine bleeding. Magnetic resonance imaging revealed a suspected ovarian tumor, and bilateral adnexectomy was performed. The preoperative serum hormone levels（luteinizing hormone, 0.5 mIU/mL follicle-stimulating hormone, ＜0.05 mIU/mL estradiol, 279 pg/mL）returned to the normal menopausal range after tumor resection（11.43 mIU/ mL, 23.80 mIU/mL, and ＜10 pg/mL, respectively）. The preoperative serum inhibin B levels were high, and the tumor tissue was diffusely immunostained with inhibin α. The woman had never experienced estrogen-deficiency symptoms. Therefore, we believe that the tumor produced inhibins initially, which led to hypogonadotropic amenorrhea that manifested as apparent early menopause, and estrogens subsequently, which caused continuous uterine bleeding over the years.

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.

BACKGROUND: Ovarian carcinomas sometimes grow in the pelvic cavity, adhering firmly to the pelvic sidewall. These cases are often considered as inoperable or result in the incomplete resection because the tumors are not mobile. We performed en bloc resection of the tumors along with the entire internal iliac vessel system to achieve complete resection. METHODS: Twenty of 237 consecutive patients with FIGO stage II-IV ovarian, fallopian tubal, or primary peritoneal carcinoma who underwent cytoreductive surgery at Chiba University Hospital between January 2008 and December 2016 had locally advanced tumors adhered firmly to the pelvic sidewall. We performed isolation of the tumors from the pelvic sidewall using the following procedure: the trunk of internal iliac vessels, the obturator vessels, the inferior gluteal and internal pudendal vessels were isolated and divided. The tumor together with the entire internal iliac vessel system was isolated from the sacral nerve plexus and piriform muscle. We examined the surgical outcomes, perioperative complications, and prognosis for the patients who underwent this procedure. RESULTS: All patients successfully underwent complete resection, resulting in no gross residual disease in the pelvic cavity. There was no mortality within 90 days postoperatively. Two patients had Grade IIIb complications, comprising wound dehiscence and vesicovaginal fistula. Recurrence occurred in nine of the patients. However, no recurrence was observed in the pelvic sidewall. The median progression-free survival was 43 months. CONCLUSIONS: Removal of the entire internal iliac vessel system is feasible for the complete resection of locally advanced ovarian carcinomas adhered firmly to the pelvic sidewall.

OBJECTIVE: Advanced ovarian cancer commonly disseminates to the diaphragm. A complete removal of a bulky diaphragmatic disease is sometimes difficult. We present the surgical technique that we used for resecting a large nodular and disseminated subphrenic tumor that occupied the subphrenic space using liver mobilization and the Pringle maneuver. METHODS: The patient was a 78-year-old woman with FIGO IIIC left ovarian carcinosarcoma. She had a metastatic subphrenic tumor measuring 12 cm in diameter. The subphrenic tumor resection was performed as a part of cytoreductive surgery. Owing to the adherence between the right diaphragm and the liver, the diaphragm was resected in full thickness. The liver was mobilized by keeping the resected part of the diaphragm attached to the liver. The subphrenic tumor and the attached diaphragm were resected en bloc by excising the liver which was adjacent to the tumor. During the resection, the hepatoduodenal ligament was clamped with a Satinsky clamp (Pringle maneuver) to reduce blood loss from the liver. The diaphragmatic defect was closed with permanent mesh. RESULTS: We achieved complete cytoreduction with no residual tumor without ICU admission. No severe intraoperative or postoperative complications were observed. The patient was discharged on postoperative day 22 and started adjuvant chemotherapy on postoperative day 27. The histological examination revealed the carcinosarcoma in the diaphragmatic peritoneum, although the carcinosarcoma did not infiltrate the adjacent liver. CONCLUSION: Resection of a metastatic bulky subphrenic tumor using liver mobilization and the Pringle maneuver is a feasible technique for the treatment of advanced ovarian cancer.

OBJECTIVE: Ovarian carcinomas sometimes metastasize to the cardiophrenic lymph node. We present a surgical technique for metastatic cardiophrenic lymph node resection following full-thickness resection of the right diaphragm. METHODS: A 51-year-old woman presented with ovarian carcinoma and cardiophrenic lymph node metastasis with peritoneal dissemination. The surgical procedure for metastatic cardiophrenic lymph node resection following full-thickness resection of the right diaphragm was as follows. (1) Stripping of the right diaphragm peritoneum was started from the ventral side toward the dorsal side. At the area where stripping was ceased due to tendon or muscle invasion, the thoracic cavity was opened. Full-thickness resection of the diaphragm was proceeded in the left-right direction. (2) The bare area was exposed. Full-thickness resection of the diaphragm was continued along the bare area. (3) After the right diaphragm resection was completed, the remaining right diaphragm was cut toward the cranial side. The metastatic cardiophrenic lymph node was grasped and pulled by forceps, and subsequently resected using a vessel-sealing device. (4) After thoracic chest tube placement, the diaphragmatic defect was closed by continuous non-absorbable sutures. RESULTS: We successfully achieved metastatic cardiophrenic lymph node resection following full-thickness resection of the right diaphragm without intra- or postoperative complications. CONCLUSION: Metastatic cardiophrenic lymph node resection is a simple procedure for gynecologic surgeons who are able to perform full-thickness resection of the diaphragm.

We herein reported a rare case of an occult fallopian tube carcinoma first detected from the diaphragm metastasis. An 83-year-old woman who had a 30-mm tumor on the right diaphragm underwent radical resection. Pathologically, the tumor was diagnosed as a high-grade serous adenocarcinoma, suggesting metastasis from the pelvic visceral carcinoma. Although the primary site could not be detected by imaging examinations, laparoscopy revealed multiple peritoneal disseminations; therefore, total hysterectomy was performed. Finally, microscopic tumor invasion into the right fimbriae of the fallopian tube was found. A precise and detailed pathological and immunohistochemical examinations of the resected metastatic diaphragm tumor helped us obtain a proper diagnosis of the primary lesion and treat the patient appropriately. Since it is difficult to diagnose diaphragm tumors before surgery based on the anatomy, surgical options have played an important role in their treatment and diagnosis clinically.

Objectives: The present study assessed whether human telomerase reverse transcriptase (TERT) promoter mutations mediate the increased mortality risk observed in patients with ovarian clear cell carcinoma (CCC) and characterized the pathologic features of TERT promoter mutation-associated ovarian CCC. Methods: The TERT promoter region in genomic DNA extracted from paraffin-embedded ovarian CCC specimens (n = 93) was bidirectionally sequenced. Results: A total of 24 TERT promoter mutations were identified among the analyzed CCC cases, of which 11 were known "hotspot" mutations whose frequency was increased in CCC cases with compared to without coexistent adenofibroma (P < .05). In contrast, the 14 (including three novel) identified uncommon site mutations were shown to be associated with a poor progression-free survival rate (P < .01). Conclusions: The identified uncommon TERT promoter mutations exacerbate the poor prognosis characteristic of ovarian CCC cases, and the hotspot mutations appear to be a molecular feature of the adenofibroma-associated form of the disease.

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: Locally advanced ovarian carcinomas may be fixed to the pelvic sidewall, and although these often involve the internal iliac vessels, they rarely involve the external iliac vessels. Such tumors are mostly considered inoperable. We present a surgical technique for complete resection of locally advanced ovarian carcinoma fixed to the pelvic sidewall and involving external and internal iliac vessels. METHODS: A 69-year-old woman presented with ovarian carcinoma fixed to the right pelvic sidewall, which involved the right external and internal iliac arteries and veins and the right lower ureter, rectum, and vagina. We cut the external iliac artery and vein at the bifurcation and at the inguinal ligament to resect the external artery and vein. Then, we reconstructed the arterial and venous supplies of the right external artery and vein with grafts. After creating a wide space immediately inside of the sacral plexus to allow the tumor fixed to pelvic sidewall with the internal iliac vessels to move medially, we performed total internal iliac vessel resection. RESULTS: We achieved complete en bloc tumor resection with the right external and internal artery and vein, right ureter, vagina, and rectum adhering to the tumor. There were no intra- or postoperative complications, such as bleeding, graft occlusion, infection, or limb edema. CONCLUSION: Exfoliation from the sacral plexus and total resection with external and internal iliac vessels enables complete resection of the tumor fixed to the pelvic sidewall.

心横隔膜角リンパ節(cardiophrenic lymph node:CPLN)は心膜に沿って2cm以内に存在する横隔膜上のリンパ節であり,進行卵巣癌において転移が認められることがある.今回,術前化学療法前にCPLNが腫大していた症例に対し,IDS(interval debulking surgery)時にCPLNを摘出した3症例を報告する.3症例は,全てで胸水が認められ,細胞診または生検にてserous carcinomaと診断されIDSが施行された.化学療法前のCTでは,CPLNの腫大は7mmを超えていた.化学療法後は縮小していたが,IDS時に摘出し,病理検査を行ったところ腫瘍細胞の遺残を認めた.遺残が再発に寄与する可能性があるため,化学療法前のCTでのCPLN腫大の評価の必要性,そして腫大が認められる場合,手術時のCPLN検索の必要性が示唆された.(著者抄録)

PURPOSE: Antiemetic recommendations during concurrent chemoradiotherapy (cisplatin-based concurrent chemoradiotherapy (CCRT)) have not been established yet. The aim of this study was to investigate whether the combination of palonosetron plus aprepitant, without routine use of dexamethasone, could alleviate chemoradiotherapy-induced nausea and vomiting (CRINV). METHODS: This was a non-randomized, prospective, single-center, open phase II study. Patients with cervical cancer, who were treated with daily low-dose cisplatin (8 mg/m(2)/day) and concurrent radiation (2 Gy/day, 25 fractions, five times a week), were enrolled in this study. All patients received intravenous palonosetron (0.75 mg on day 1 of each week) and oral aprepitant (125 mg on day 1 and 80 mg on days 2 and 3 of each week). The primary endpoint was the percentage of patients with a complete response, defined as no emetic episodes and no use of antiemetic rescue medication during the treatment. RESULTS: Twenty-seven patients (median age, 50 years; range, 33-72 years) were enrolled in this study between June 2013 and April 2014. A total of 13 (48 %) patients showed a complete response to the antiemetic regimen, while 8 patients (30 %) had emetic episodes and 6 patients (22 %) used rescue medication without emetic episodes. No severe adverse effects caused by palonosetron plus aprepitant were observed. CONCLUSION: The combination of palonosetron plus aprepitant was permissive for the prevention of CRINV. This regimen should be considered for patients in whom dexamethasone is contraindicated or not well tolerated.

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.