研究者業績

楯 真一

タテ シンイチ  (Shinichi Tate)

基本情報

所属
千葉大学 大学院医学研究院発生・再建医学研究部門発生医学講座生殖機能病態学 講師

J-GLOBAL ID
201001007522201913
researchmap会員ID
6000022325

論文

 58
  • TOMOE YAZAKI, AYUMU MATSUOKA, SHINICHI TATE, KYOKO NISHIKIMI, RIE OKUYA, SATOYO OTSUKA, KAORI KOGA, HIROKAZU USUI
    Cancer Diagnosis & Prognosis 4(4) 454-458 2024年7月1日  
    Background/Aim: Upper gastrointestinal obstruction is an extremely rare complication of primary ovarian cancer. We present a case of primary advanced ovarian cancer with gastroduodenal obstruction successfully managed with neoadjuvant chemotherapy (NAC) and conservative treatment. Case Report: A 60-year-old woman was referred to our hospital for advanced ovarian cancer with upper gastrointestinal obstruction. Computed tomography and endoscopy revealed severe duodenal obstruction caused by dissemination. NAC was initiated with conservative management using a nasogastric tube and total parenteral nutrition (TPN). She was able to eat and TPN was stopped after three months. Complete resection was achieved with interval debulking surgery (IDS) not involving pancreatoduodenectomy, which would have been necessary for primary debulking surgery. There were no serious postoperative complications. Conclusion: NAC with conservative management can improve upper gastrointestinal obstruction in patients with primary advanced ovarian cancer. Furthermore, IDS is expected to allow complete resection, avoiding highly invasive surgeries.
  • Tomoe Yazaki, Ayumu Matsuoka, Shinichi Tate, Kyoko Nishikimi, Rie Okuya, Satoyo Otsuka, Kaori Koga, Hirokazu Usui
    Cancer diagnosis & prognosis 4(4) 454-458 2024年  
    BACKGROUND/AIM: Upper gastrointestinal obstruction is an extremely rare complication of primary ovarian cancer. We present a case of primary advanced ovarian cancer with gastroduodenal obstruction successfully managed with neoadjuvant chemotherapy (NAC) and conservative treatment. CASE REPORT: A 60-year-old woman was referred to our hospital for advanced ovarian cancer with upper gastrointestinal obstruction. Computed tomography and endoscopy revealed severe duodenal obstruction caused by dissemination. NAC was initiated with conservative management using a nasogastric tube and total parenteral nutrition (TPN). She was able to eat and TPN was stopped after three months. Complete resection was achieved with interval debulking surgery (IDS) not involving pancreatoduodenectomy, which would have been necessary for primary debulking surgery. There were no serious postoperative complications. CONCLUSION: NAC with conservative management can improve upper gastrointestinal obstruction in patients with primary advanced ovarian cancer. Furthermore, IDS is expected to allow complete resection, avoiding highly invasive surgeries.
  • Mana Haruishi, Ayumu Matsuoka, Shinichi Tate, Takayuki Arai, Tomohiko Ichikawa, Hirokazu Usui
    The journal of obstetrics and gynaecology research 2023年2月15日  
    Asymptomatic hydronephrosis following hysterectomy is generally transient. Here, we present the case of a 52-year-old woman who underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy for benign indications. Computed tomography (CT) to examine bleeding on the second postoperative day incidentally revealed bilateral grade II hydronephrosis. Asymptomatic hydronephrosis was not reevaluated, and gynecological outpatient follow-up was terminated with a normal creatinine level on postoperative day 43. On postoperative day 107, the patient noticed weight gain of 10 kg, decreased urine output, and generalized edema. The serum creatinine level was elevated to 5.4 mg/dL, and CT revealed bilateral grade III hydronephrosis. Urgent bilateral ureteral stenting was performed to treat stenosis of the distal ureters that caused postrenal failure. Ureteroneocystostomy was performed for strict stenosis of the right ureter at 10 months postoperatively. Histological examination of the resected distal ureter showed inflammation and fibrosis. Asymptomatic hydronephrosis developing after hysterectomy progress to delayed postrenal failure.
  • Tatsuya Kobayashi, Kyoko Nishikimi, Akira Mitsuhashi, Hongying Piao, Ayumu Matsuoka, Satoyo Otsuka, Shinichi Tate, Makio Shozu, Hirokazu Usui
    Genes, chromosomes & cancer 2023年1月29日  
    Several cancers harbor "enhancer-type" mutations of the telomerase reverse transcriptase (TERT) promoter for immortalization. Here, we report that 8.6% (8/93) of ovarian clear cell carcinomas (OCCCs) possess the "suppressor-type" TERT promoter mutation. The recurrence rate of OCCCs with "suppressor-type" TERT promoter mutations was 62.5% (5 of 8) and was significantly higher than that of the "unaffected-type" with no mutation (20.8%, 15 of 72) or "enhancer-type" TERT promoter mutations (7.7%, 1 of 13). Our findings show that the acquired suppression of TERT is closely associated with OCCC development and recurrence, indicating the need for further research on telomerase suppression in cancers.
  • 勝浦 瑞貴, 松岡 歩, 楯 真一, 錦見 恭子, 羽生 裕二, 中村 名津子, 奥谷 理恵, 片山 恵里, 大塚 聡代, 碓井 宏和
    関東連合産科婦人科学会誌 59(3) 350-350 2022年10月  
  • Shinichi Tate, Kyoko Nishikimi, Ayumu Matsuoka, Satoyo Otsuka, Makio Shozu
    Anticancer research 42(7) 3707-3716 2022年7月  
    BACKGROUND/AIM: We investigated whether highly aggressive surgery has survival and perioperative complication benefit in patients with advanced ovarian cancer. PATIENTS AND METHODS: This retrospective study included 209 patients with stage III/IV ovarian cancer who underwent aggressive surgery [surgical complexity score (SCS) ≥8] between January 2008 and December 2018. Patients were categorized into the SCS 8-12 (less aggressive surgery, 83 patients) and SCS ≥13 (highly aggressive surgery, 126 patients) groups. Survival outcomes and perioperative complications between the groups were compared. Patient suitability for primary debulking surgery or neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) was based on the evaluation of performance status, tumor load, and ascites. If patients were suitable for NACT/IDS, the residual tumor margins were marked at the initial laparotomy. The previously marked lesions were removed during IDS, even in patients with macroscopic tumor resolution. RESULTS: Prevalence rates of stage IV disease, poor performance status, presence of omental cake, peritoneal cancer index ≥15, and IDS performed were significantly higher in the highly aggressive surgery group than in the less aggressive surgery group. The median progression-free survival (PFS) and overall survival (OS) were not significantly different between the groups (PFS, 32 and 31 months, respectively; p=0.622; OS, 99 and 75 months, respectively; p=0.390). The incidence of severe perioperative complications was not significantly different between the less aggressive group (4.8%) and the highly aggressive surgery group (6.4%) (p=0.767). CONCLUSION: Highly aggressive surgery with appropriate selection regardless of the timing of cytoreduction benefits patients with advanced ovarian cancer.
  • Shinichi Tate, Kyoko Nishikimi, Ayumu Matsuoka, Satoyo Otsuka, Makio Shozu
    Anticancer research 42(5) 2637-2644 2022年5月  
    BACKGROUND/AIM: Brain metastases from ovarian cancer remain rare and the appropriate treatment is unknown. We investigated survival outcomes following salvage chemotherapy before and after bevacizumab approval to evaluate the efficacy of bevacizumab in patients with brain metastasis from ovarian cancer. PATIENTS AND METHODS: We investigated 23 consecutive patients with brain metastasis from ovarian cancer at our hospital between 2001 and 2020. Bevacizumab was administered for treating ovarian cancer after approval in Japan in November 2013. Survival after brain metastasis was compared between 9 patients treated before bevacizumab approval (2000-2013) and 14 patients treated after approval (2014-2020). Seven patients treated in the latter period received bevacizumab-salvage chemotherapy for brain metastasis. RESULTS: Median survival in all patients was 9.1 months [95% confidence interval (CI)=4.2-33.5]. In addition, patients treated during the latter period presented better survival outcomes than those treated in the former period (former, 2.9 months vs latter, 33.5 months, log-rank test, p=0.015; Wilcoxon test, p=0.009). Multivariate analysis revealed that bevacizumab addition (p=0.020), interval to brain metastasis (p=0.005), number of brain lesions (p=0.001), number of recurrences (p=0.001), and platinum sensitivity (p=0.028) were independently associated with survival in all cohorts. CONCLUSION: Bevacizumab-based salvage chemotherapy may improve survival outcomes in patients with brain metastasis.
  • Kyoko Nishikimi, Shinichi Tate, Ayumu Matsuoka, Satoyo Otsuka, Makio Shozu
    Journal of gynecologic oncology 33(3) e30 2022年1月20日  
    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.
  • Ayumu Matsuoka, Shinichi Tate, Satoyo Otsuka, Kyoko Nishikimi, Makio Shozu
    Acta cytologica 66(5) 426-433 2022年  
    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.
  • Kyoko Nishikimi, Shinichi Tate, Ayumu Matsuoka, Satoyo Otsuka, Makio Shozu
    Cancers 13(16) 2021年8月23日  
    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.
  • Ayumu Matsuoka, Shinichi Tate, Satoyo Otsuka, Kyoko Nishikimi, Makio Shozu
    International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 31(7) 1087-1087 2021年7月  
  • Shinichi Tate, Kyoko Nishikimi, Ayumu Matsuoka, Satoyo Otsuka, Yuki Shiko, Yoshihito Ozawa, Yohei Kawasaki, Makio Shozu
    Cancers 13(13) 3177-3177 2021年6月25日  査読有り
    (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.
  • Shinichi Tate, Kyoko Nishikimi, Ayumu Matsuoka, Satoyo Otsuka, Makio Shozu
    International journal of clinical oncology 26(5) 986-994 2021年5月  
    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.
  • Shinichi Tate, Kyoko Nishikimi, Ayumu Matsuoka, Satoyo Otsuka, Makio Shozu
    Cancers 13(4) 2021年2月5日  
    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.
  • Shinichi Tate, Kyoko Nishikimi, Ayumu Matsuoka, Satoyo Otsuka, Kazuyoshi Kato, Yutaka Takahashi, Makio Shozu
    Journal of gynecologic oncology 32(1) e8 2021年1月  
    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.
  • Kyoko Nishikimi, Shinichi Tate, Ayumu Matsuoka, Makio Shozu
    Scientific reports 10(1) 21307-21307 2020年12月4日  
    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.
  • Shinichi Tate, Kyoko Nishikimi, Ayumu Matsuoka, Makio Shozu
    International journal of clinical oncology 25(9) 1726-1735 2020年9月  
    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.
  • 竹原 直希, 羽生 裕二, 三橋 暁, 松岡 歩, 錦見 恭子, 楯 真一, 碓井 宏和, 生水 真紀夫
    関東連合産科婦人科学会誌 57(2) 218-218 2020年6月  
  • Shinichi Tate, Kyoko Nishikimi, Kazuyoshi Kato, Ayumu Matsuoka, Michiyo Kambe, Takako Kiyokawa, Makio Shozu
    Journal of gynecologic oncology 31(3) e34 2020年5月  
    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.
  • Kyoko Nishikimi, Shinichi Tate, Ayumu Matsuoka, Nozomu Sakai, Masayuki Otsuka, Makio Shozu
    Gynecologic oncology 157(2) 555-557 2020年5月  
    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.
  • Kyoko Nishikimi, Shinichi Tate, Ayumu Matsuoka, Makio Shozu
    Gynecologic oncology 156(1) 54-61 2020年1月  
    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.
  • Kyoko Nishikimi, Shinichi Tate, Ayumu Matsuoka, Makio Shozu
    International journal of clinical oncology 24(8) 941-949 2019年8月  
    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.
  • Ayumu Matsuoka, Shinichi Tate, Kyoko Nishikimi, Makio Shozu
    Gynecologic oncology 151(2) 390-391 2018年11月  
  • 松岡 歩, 三橋 暁, 錦見 恭子, 楯 真一, 生水 真紀夫
    日本癌治療学会学術集会抄録集 56回 P95-1 2018年10月  
  • Kyoko Nishikimi, Shinichi Tate, Ayumu Matsuoka, Makio Shozu
    Gynecologic oncology 151(1) 176-177 2018年10月  
    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.
  • Kyoko Nishikimi, Shinichi Tate, Ayumu Matsuoka, Makio Shozu
    Gynecologic oncology 150(3) 581-583 2018年9月  
    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.
  • Ayumu Matsuoka, Shinichi Tate, Kyoko Nishikimi, Makio Shozu
    Gynecologic oncology 149(2) 430-431 2018年5月  
  • Kyoko Nishikimi, Kiyoshi Nakagawa, Shinichi Tate, Ayumu Matsuoka, Masami Iwamoto, Takako Kiyokawa, Makio Shozu
    American journal of clinical pathology 149(4) 352-361 2018年3月7日  
    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.
  • Ayumu Matsuoka, Shinichi Tate, Kyoko Nishikimi, Makio Shozu
    Gynecologic oncology 148(3) 632-633 2018年3月  
    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.
  • Shinichi Tate, Kazuyoshi Kato, Kyoko Nishikimi, Ayumu Matsuoka, Makio Shozu
    GYNECOLOGIC ONCOLOGY 147(1) 73-80 2017年10月  査読有り
    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 5 years after implementing an aggressive surgery protocol. After receiving appropriate training for 9 months, 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 debulldng 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 38.1 months before implementation, respectively, to 25.0 and 68.5 months after implementation, respectively. Complete resection was achieved in 83 of the 106 patients (78%), and the surgical complexity score was high (&gt;8) in 61 patients (58%); although there was no mortality within 12 weeks 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. (C) 2017 Elsevier Inc. All rights reserved.
  • Akira Mitsuhashi, Hirokazu Usui, Kyoko Nishikimi, Noriko Yamamoto, Shinsuke Hanawa, Shinichi Tate, Miho Watanabe-Nemoto, Takashi Uno, Makio Shozu
    American journal of clinical oncology 40(2) 118-121 2017年4月  
    OBJECTIVES: The prevention of chemotherapy-induced and radiotherapy-induced emesis is recommended by several guidelines; however, there are no evidence-based recommendations for the use of antiemetics in concurrent chemoradiotherapy (CCRT). The aim of the present study was to evaluate the efficacy and safety of antiemetic therapy comprising palonosetron and dexamethasone during CCRT. METHODS: This is a nonrandomized, prospective, single-center, open phase II study.Twenty-six consecutive patients with cervical carcinoma were treated with daily low-dose cisplatin (8 mg/m/d)-based CCRT (2 Gy/d, 25 fractions, 5 times a week). All patients received 0.75 mg of palonosetron on day 1 of each week and 4 mg of oral dexamethasone daily. The primary endpoint was the percentage of patients achieving a complete response, which was defined as no emetic episodes and no antiemetic rescue medication during treatment. RESULTS: Planned daily low-dose cisplatin-based CCRT was successful without delay or interruption in 46% (12/26) of the patients. The mean dose of total cisplatin was 184 (range, 136 to 200) mg/m.No patient vomited during the treatment period. The complete response rate during CCRT was 100%. A total of 81% patients were completely free from nausea. All patients tolerated the combination of palonosetron and dexamethasone and completed the scheduled regimen. Five patients exhibited grade 1 Cushingoid features that resolved after treatment. CONCLUSIONS: Antiemetic therapy comprising palonosetron and dexamethasone provided complete protection from nausea and vomiting in patients with cervical cancer receiving daily low-dose cisplatin-based CCRT.
  • 鉄林 諭慧, 楯 真一, 松岡 歩, 錦見 恭子, 塙 真輔, 碓井 宏和, 三橋 暁, 生水 真紀夫
    関東連合産科婦人科学会誌 54(1) 73-78 2017年3月  
    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)
  • Akira Mitsuhashi, Hirokazu Usui, Kyoko Nishikimi, Noriko Yamamoto, Shinsuke Hanawa, Shinichi Tate, Miho Watanabe-Nemoto, Takashi Uno, Makio Shozu
    American Journal of Clinical Oncology: Cancer Clinical Trials 40(2) 118-121 2017年  査読有り
    Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved. Objectives: The prevention of chemotherapy-induced and radiotherapy-induced emesis is recommended by several guidelines; however, there are no evidence-based recommendations for the use of antiemetics in concurrent chemoradiotherapy (CCRT). The aim of the present study was to evaluate the efficacy and safety of antiemetic therapy comprising palonosetron and dexamethasone during CCRT. Methods: This is a nonrandomized, prospective, single-center, open phase II study. Twenty-six consecutive patients with cervical carcinoma were treated with daily low-dose cisplatin (8 mg/m 2 /d)-based CCRT (2 Gy/d, 25 fractions, 5 times a week). All patients received 0.75 mg of palonosetron on day 1 of each week and 4 mg of oral dexamethasone daily. The primary endpoint was the percentage of patients achieving a complete response, which was defined as no emetic episodes and no antiemetic rescue medication during treatment. Results: Planned daily low-dose cisplatin-based CCRT was successful without delay or interruption in 46% (12/26) of the patients. The mean dose of total cisplatin was 184 (range, 136 to 200) mg/m 2. No patient vomited during the treatment period. The complete response rate during CCRT was 100%. A total of 81% patients were completely free from nausea. All patients tolerated the combination of palonosetron and dexamethasone and completed the scheduled regimen. Five patients exhibited grade 1 Cushingoid features that resolved after treatment. Conclusions: Antiemetic therapy comprising palonosetron and dexamethasone provided complete protection from nausea and vomiting in patients with cervical cancer receiving daily low-dose cisplatin-based CCRT.
  • Shinsuke Hanawa, Akira Mitsuhashi, Ayumu Matsuoka, Kyoko Nishikimi, Shinichi Tate, Hirokazu Usui, Takashi Uno, Makio Shozu
    Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer 24(11) 4633-8 2016年11月  
    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.
  • Hirokazu Usui, Takako Kiyokawa, Jia Qu, Kyoko Nishikimi, Shinichi Tate, Akira Mitsuhashi, Yukio Nakatani, Makio Shozu
    JOURNAL OF REPRODUCTIVE MEDICINE 61(5-6) 219-223 2016年5月  査読有り
    OBJECTIVE: To elucidate the diagnostic accuracy of macroscopic and histopathological diagnoses of molar pregnancy as compared with cytogenetic diagnosis as the gold standard. STUDY DESIGN: Patients were recruited for the molecular diagnostic study of suspected molar pregnancy at Chiba University Hospital between 2007 and 2011. Gynecologists performed macroscopic diagnoses immediately after the evacuation. Pathological diagnoses were then made by pathologists in routine bases without performing p57Kip2 immunostaining. Molecular cytogenetic diagnosis was performed via short tandem repeat (STR) polymorphism analysis. Androgenetic, biparental triploid, and biparental diploid odious tissues determined on STR polymorphism analysis were classified as complete hydatidiform mole (CHM), partial hydatidiform mole (PHM), and abortion, respectively. RESULTS: A total of 86 patients were enrolled. The number of CHMs, PHMs, and abortions on cytogenetic diagnoses were 64; 9, and 13, respectively. The concordance rate between macroscopic and cytogenetic diagnoses was 85% (CHM: 56, PHM: 4, and abortions: 13). The concordance rate between histopathological and cytogenetic diagnoses was 87% (CHM: 59, PHM: 5, and abortions: 10). The complete agreement rate among the 3 categories was 78% (CHM: 55, PHM: 3, and abortions: 10). CONCLUSION: Neither macroscopic nor histopathological diagnoses were perfect, but both were quite accurate in a single trophoblastic center.
  • Ayumu Matsuoka, Shinichi Tate, Kyoko Nishikimi, Hiroshi Ishikawa, Makio Shozu
    Menopause (New York, N.Y.) 23(5) 544-9 2016年5月  
    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.
  • Kyoko Nishikimi, Takako Kiyokawa, Shinichi Tate, Masami Iwamoto, Makio Shozu
    Histopathology 67(6) 866-71 2015年12月  
    AIMS: The carcinogenesis of ovarian clear cell carcinoma (CCC) has been hypothesized to comprise two different pathways: an adenofibroma-carcinoma sequence and an endometriosis-carcinoma sequence. However, the difference in the genetic basis of these two pathways remains unclear. Recent studies have suggested that an ARID1A mutation and the loss of the corresponding protein, BAF250a, are frequent events in CCC. Herein, we investigated the difference in the loss of BAF250a expression in adenofibroma-related CCC and endometriosis-related CCC. METHODS AND RESULTS: In total, 93 cases of surgically treated CCC were evaluated. The presence of adenofibroma and endometriosis associated with carcinoma was determined by reviewing haematoxylin and eosin-stained slides for each case. BAF250a expression in carcinoma was examined immunohistochemically. The loss of BAF250a expression was detected in carcinomas in 50 of 93 (54%) cases, including five of 18 (28%) with adenofibroma alone, 30 of 45 (67%) with endometriosis alone, eight of 18 (44%) with both conditions and seven of 12 (58%) with neither condition. The loss of BAF250a expression was significantly less frequent in CCC cases with adenofibroma than in cases with endometriosis (P = 0.01, Fisher's exact test). CONCLUSIONS: The action of ARID1A in carcinogenesis differs between adenofibroma-related CCC and endometriosis-related CCC.
  • Kazuyoshi Kato, Kyoko Nishikimi, Shinichi Tate, Takako Kiyokawa, Makio Shozu
    World journal of surgical oncology 13 230-230 2015年7月31日  
    BACKGROUND: To achieve optimal cytoreduction for advanced-stage ovarian cancer, modified posterior exenteration is the most frequently performed bowel surgery. We assessed the extents of tumor spreading in the rectosigmoid wall and pelvic side wall in modified posterior exenteration specimens during primary debulking surgery (PDS) and interval debulking surgery (IDS) following neoadjuvant chemotherapy, and compared the validity of selecting this surgical procedure in the patients undergoing PDS with that in the patients undergoing IDS. METHODS: Clinicopathological data from consecutive patients who had undergone a modified posterior exenteration for primary ovarian, tubal, and peritoneal cancer at our institution between April 2008 and March 2013 was retrospectively reviewed. RESULTS: A total of 75 patients (38 in PDS and 37 in IDS) were included in this study. Tumor involvement of the rectosigmoid was histopathologically confirmed in 65% of the specimens. Though the extent of tumor spreading in the rectosigmoid was deeper in PDS than in IDS, the frequency of tumor involvement of the rectosigmoid in patients who had undergone modified posterior exenteration during PDS was equivalent to that in the IDS group. Lateral tumor spreading to the side wall(s) was histopathologically confirmed in 53% of the patients in whom a pelvic side wall resection had been performed. CONCLUSIONS: During both PDS and IDS for ovarian cancer presenting with tumor involvement of the cul-de-sac, close inspection and palpation by gynecologic oncologists may enable the extent of tumor spreading in the pelvis to be estimated, enabling valid decisions as to whether an en bloc resection of the pelvic tumors together with the rectosigmoid and the pelvic side wall might or might not be appropriate.
  • Shinsuke Hanawa, Akira Mitsuhashi, Hirokazu Usui, Noriko Yamamoto, Miho Watanabe-Nemoto, Kyoko Nishikimi, Takashi Uehara, Shinichi Tate, Takashi Uno, Makio Shozu
    International Journal of Gynecological Cancer 25(5) 891-896 2015年6月4日  査読有り
    © 2015 by IGCS and ESGO. Objectives It has been established that concurrent chemoradiotherapy (CCRT) is efficacious for cervical cancer, but adherence is unsatisfactory among elderly patients. To improve adherence, we have developed and initiated a daily low-dose cisplatin-based CCRT regimen. Here, we retrospectively evaluated the use of CCRT, especially for elderly patients. Methods The study included a total of 53 patients who were 70 years or older, had stage IB-IVA cervical cancer, and were initially treated with daily CCRT. The daily CCRT comprised pelvic external beam radiotherapy (2 Gy/d × 25) with daily low-dose cisplatin (8.0 mg/m 2 per day) and either low- or high-dose-rate intracavitary brachytherapy. Results The median age was 72 years (range, 70-85 years). The median follow-up duration was 32 months (range, 2-104 months). The 3-year overall survival rate was 79.0%. Daily cisplatin chemotherapy was successfully completed in 32 (60.4%) of the 53 patients. Grade 3 or 4 neutropenia was observed in 19 patients (36%). A late complication of grade 3 rectal hemorrhage occurred in 3 patients who received high-dose-rate brachytherapy. All primary tumors responded to daily CCRT; complete response was observed in 43 patients (91.5%) and partial response was observed in 4 patients (8.5%). Conclusions Daily CCRT in patients 70 years and older had acceptable compliance and safety. Daily CCRT is suggested to be a good treatment option for elderly patients who have advanced cervical cancer and require concurrent cisplatin.
  • Kazuyoshi Kato, Shinichi Tate, Kyoko Nishikimi, Makio Shozu
    Journal of gynecologic oncology 25(1) 64-9 2014年1月  
    OBJECTIVE: Compression of the left common iliac vein between the right common iliac artery and the vertebrae is known to be associated with the occurrence of left iliofemoral deep vein thrombosis (DVT). In this study, we described the variability in vascular anatomy of the common iliac veins and evaluated the relationship between the degree of iliac vein compression and the presence of DVT using the data from surgeries for gynecologic cancer. METHODS: The anatomical variations and the degrees of iliac vein compression were determined in 119 patients who underwent systematic para-aortic and pelvic lymphadenectomy during surgery for primary gynecologic cancer. Their medical records were reviewed with respect to patient-, disease-, and surgery-related data. RESULTS: THE DEGREES OF COMMON ILIAC VEIN COMPRESSION WERE CLASSIFIED INTO THREE GRADES: grade A (n=28, 23.5%), with a calculated percentage of 0%-25% compression; grade B (n=47, 39.5%), with a calculated percentage of 26%-50% compression; and grade C (n=44, 37%), with a calculated percentage of more than 50% compression. Seven patients (5.9%) had common iliac veins with anomalous anatomies; three were divided into small caliber vessels, two with a flattened structure, and two had double inferior vena cavae. The presence of DVT was associated with the elevated D-dimer levels but not with the degree of iliac vein compression in this series. CONCLUSION: Although severe compression of the common iliac veins was frequently observed, the degree of compression might not be associated with DVT in surgical patients with gynecologic cancer. Anomalous anatomies of common iliac veins should be considered during systematic para-aortic and pelvic lymphadenectomy in the gynecologic cancer patients.
  • Akira Mitsuhashi, Takashi Uno, Hirokazu Usui, Kyoko Nishikimi, Noriko Yamamoto, Miho Watanabe, Shinichi Tate, Koichiro Hirashiki, Kazuyoshi Kato, Koji Yamazawa, Makio Shozu
    International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 23(8) 1453-8 2013年10月  
    OBJECTIVE: We evaluated the usefulness of daily low-dose cisplatin-based concurrent chemoradiotherapy (daily CCRT) in patients with cervical cancer with an emphasis on elderly patients. METHODS: Between January 2003 and December 2008, a total of 65 patients with untreated stage IIA to IIIB cervical cancer were enrolled and 54 were selected for this nonrandomized prospective study. The daily CCRT comprised pelvic external beam radiotherapy (2 Gy/d × 25) with daily low-dose cisplatin (8.0 mg/m(2) per day) and either low- or high-dose rate intracavitary brachytherapy. RESULTS: The median age of the patients was 62 years (range, 29-85 years), and 21 patients (39%) were 70 years or older. The median follow-up period was 47 months (range, 4-107 months). Daily CCRT was successfully completed in 91% (49/54) of the patients. The mean total cisplatin dose was 191 mg/m (range, 128-224 mg/m(2)), and a neutropenia grade higher than 3 was observed in 24% of the patients. Of the 21 patients 70 years or older, 17 (81%) completed daily CCRT with acceptable toxicity. The 3-year overall survival (OS) rate for all the patients was 82.9%. No statistically significant differences in the OS rate and toxicity were observed between patients 70 years or older and those younger than 70 years. CONCLUSIONS: Daily CCRT showed acceptable toxicity and compliance, leading to the use of a high total dosage of cisplatin. The OS rate for daily CCRT was comparable to that for previously reported weekly CCRT. Daily CCRT could be an alternate choice for the CCRT treatment in elderly patients with cervical cancer.
  • Kazuyoshi Kato, Shinichi Tate, Kyoko Nishikimi, Makio Shozu
    Gynecologic oncology 131(1) 32-5 2013年10月  
    OBJECTIVE: The present study assessed the use of an intraoperative tube thoracostomy for patients with primary advanced-stage ovarian, fallopian tube, or peritoneal cancer who underwent a diaphragmatic resection as part of debulking surgery and to define which patients are more likely to benefit from an intraoperative tube thoracostomy. METHODS: All consecutive patients with stage IIIC-IV Müllerian cancer who underwent diaphragmatic resection at our institution between April 2008 and March 2013 were retrospectively reviewed. When a full-thickness resection of the diaphragm was performed and the thoracic cavity was opened, a chest tube was routinely placed during surgery. Patient-, disease-, and surgery-related data were collected from the patients' medical records. The data were evaluated with particular attention directed at pleural effusion after diaphragmatic resection. RESULTS: A total of 37 patients were included in this study. No complications associated with the intraoperative tube thoracostomy procedures occurred. An infection of the thoracic cavity occurred in one patient, following the presence of intra-abdominal abscess. The total volume of pleural drainage ranged from 88 to 2826 mL (median, 965 mL). The estimated blood loss, intraoperative blood transfusion, and area of the diaphragmatic opening were significantly associated with the total volume of pleural drainage in univariate analyses. In a multivariate analysis, the estimated blood loss was the only factor to be significantly associated with the total volume of pleural drainage. CONCLUSIONS: A prophylactic tube thoracostomy might be considered if the volume of the estimated blood loss is higher than usual.
  • Kazuyoshi Kato, Shinichi Tate, Kyoko Nishikimi, Makio Shozu
    International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 23(8) 1506-11 2013年10月  
    OBJECTIVE: This study evaluated the incidence of postoperative morbidities, focusing specifically on pancreatic fistulas, after a splenectomy performed as part of cytoreductive surgery for the treatment of ovarian cancer. METHODS: A retrospective chart review was performed for all the patients with ovarian, tubal, or peritoneal cancer who underwent splenectomy during a 5-year period. Patient-, disease-, and surgery-related data were collected. Pancreatic fistulas were identified when the drainage fluid obtained via a surgically placed drain had an amylase content greater than 3 times the normal serum value after postoperative day 3. RESULTS: A splenectomy was performed in 21 patients. Postoperative pancreatic fistulas developed in 6 patients (29%). Of these 6 patients, 2 had no symptoms and did not require specific treatment for their pancreatic fistulas. Therapeutic intervention was required in the remaining 4 patients. The durations of oral feeding prohibition and the use of a peripancreatic drain were longer in the patients with a pancreatic fistula than in those without a pancreatic fistula. Overall, the pancreatic fistulas were managed conservatively or using minimally invasive procedures. Staple-line reinforcement seemed to be an effective means of closing the transected stump during the splenectomy, compared with the standard stapling technique. CONCLUSIONS: Elevated amylase levels in the drainage fluid reflect the patient's actual condition better than serum amylase levels. We recommend the intraoperative placement of a peripancreatic drain and postoperative measurement of amylase concentrations in the drainage fluid to identify the development of pancreatic fistulas and to facilitate the management of this complication.
  • Shinsuke Akita, Nobuyuki Mitsukawa, Naoaki Rikihisa, Yoshitaka Kubota, Naoko Omori, Akira Mitsuhashi, Shinichi Tate, Makio Shozu, Kaneshige Satoh
    Plastic and reconstructive surgery 132(3) 471e-472e 2013年9月  
  • Shinsuke Akita, Nobuyuki Mitsukawa, Naoaki Rikihisa, Yoshitaka Kubota, Naoko Omori, Akira Mitsuhashi, Shinichi Tate, Makio Shozu, Kaneshige Satoh
    Plastic and reconstructive surgery 132(3) 473e-474e 2013年9月  
  • 楯 真一, 錦見 恭子, 山本 憲子, 植原 貴史, 碓井 宏和, 三橋 暁, 生水 真紀夫, 加藤 一喜
    日本婦人科腫瘍学会雑誌 31(2) 114-119 2013年4月  
    2000年から2011年の進行卵巣がん手術94例を標準術式中心の前期47例と拡大術式を積極的に採用した後期47例に分けて治療成績を比較した。progression free survival(PFS)は前期14.6ヵ月、後期21.2ヵ月と有意に改善した。治療内容は、前期でprimary debulking surgery(PDS)を6例、intervaldebulking surgery(IDS)を41例に行い、PFSはそれぞれ11ヵ月、15ヵ月と有意差はなかった。後期はPDSが15例、IDSが32例で、PFSはPDSでは中央値に達しておらず、IDSは21ヵ月であった。optimal rateは前期57.5%、後期89.4%で、PDSでは33.3%から93.3%に、IDSでは61%から87.5%に上昇した。術式は、前期で子宮全摘・両側付属器・大網切除(基本術式)が22例、基本術式+結腸切除が12例、基本術式+結腸・横隔膜全層分層切除(+膵尾部合併脾臓摘出)が1例、no debulking surgeryが12例、後期はそれぞれ3例、12例、28例、4例であった。
  • Kazuyoshi Kato, Shinichi Tate, Kyoko Nishikimi, Makio Shozu
    Gynecologic oncology 129(1) 229-33 2013年4月  
    OBJECTIVE: Bladder dysfunction caused by autonomic nerve injury is a well-recognized complication of pelvic surgery. Modified posterior exenteration with or without nerve preservation was performed in patients with primary ovarian, tubal, peritoneal, and endometrial cancer. The aim of this retrospective study was to evaluate the impact of this surgical technique on bladder function. METHODS: Among the 60 consecutive patients in whom modified posterior exenteration was performed, bilateral and unilateral nerve-sparing surgeries were performed in 43 (72%) and 15 (25%) patients, respectively. In the remaining 2 patients (3%), the pelvic autonomic nerves on both sides were sacrificed. Symptoms and bladder function after bilateral or unilateral nerve-sparing surgery were analyzed using standardized questionnaires before and 3 and 6 months after surgery. RESULTS: All patients with bilateral nerve-sparing surgery had sufficient micturition from the early postoperative period. Though 40% of the patients with unilateral nerve-sparing surgery had difficulty in spontaneous voiding and needed intermittent catheterization, voiding ability of them improved and no self-catheterization was required 3 months after surgery. The assessment of patient questionnaires suggested that bladder function was acceptable in both groups at 6 months. Patients with bilateral nerve-sacrificing surgery complained of neurogenic bladder requiring self-catheterization even 6 months after surgery. CONCLUSIONS: This preliminary study showed that preservation of bladder function after modified posterior exenteration was feasible with a nerve sparing approach and that standardized outcome measures could be used to monitor this. However, careful follow-up is required. Future larger studies are needed to investigate pelvic autonomic nerve function.
  • Shinsuke Akita, Nobuyuki Mitsukawa, Naoaki Rikihisa, Yoshitaka Kubota, Naoko Omori, Akira Mitsuhashi, Shinichi Tate, Makio Shozu, Kaneshige Satoh
    Plastic and reconstructive surgery 131(2) 283-290 2013年2月  
    BACKGROUND: Although early diagnosis is important for selecting an effective surgical treatment for secondary lymphedema, an efficient screening test for detecting early-stage lymphedema has not yet been established. Serial changes of lymphatic function before and after lymph node dissection and risk factors for secondary lymphedema are important indicators. METHODS: A prospective cohort observational study was conducted with 100 consecutive gynecologic cancer patients who underwent pelvic lymph node dissection. Lymphatic function was assessed by noninvasive lymphography using indocyanine green fluorescence imaging on a routine schedule. Earliest findings after lymphadenectomy and risk factors for lower leg lymphedema were investigated. RESULTS: Atypical transient dermal backflow patterns were observed in an early postoperative period in 50 cases, all of which disappeared within 3 months. Of these patterns, the splash pattern was observed in 31 patients, of which five improved to normal following a natural course. In contrast, the stardust pattern was observed in 27 patients, and none had improved with conservative therapy. Postoperative radiotherapy was a significant risk factor for the stardust pattern. CONCLUSIONS: All patients who undergo lymphadenectomy for gynecologic malignancies should be examined for secondary lower extremity lymphedema by qualitative evaluation methods on a routine schedule to determine the earliest possible diagnosis. Because the splash pattern on indocyanine green lymphography is a reversible lymphatic disorder following a natural course, surgical treatments are not recommended. The decision regarding surgical treatment can be made after observing the stardust pattern. CLINICAL QUESTION/LEVEL OF EVIDENCE: Diagnostic, IV.
  • Kato K, Tate S, Uehara T, Usui H, Mitsuhashi A, Shozu M
    Eur J Gynaecol Oncol 32(5) 579-581 2011年5月  査読有り
  • 木原 真紀, 碓井 宏和, 楯 真一, 加来 博志, 藤田 真紀, 三橋 暁, 長田 久夫, 生水 真紀夫
    日本産科婦人科学会雑誌 63(2) 699-699 2011年2月  査読有り

MISC

 98
  • 小林達也, 錦見恭子, 三橋暁, 三橋暁, 松岡歩, 大塚聡代, 楯真一, 生水真紀夫, 碓井宏和, 甲賀かをり
    日本遺伝子診療学会大会プログラム・抄録集 30th 2023年  
  • 伊藤 孝輔, 松岡 歩, 大塚 聡代, 羽生 裕二, 錦見 恭子, 楯 真一, 碓井 宏和, 三橋 暁, 椎名 愛優, 岸本 充, 池田 純一郎, 生水 真紀夫
    日本婦人科腫瘍学会学術講演会プログラム・抄録集 63回 318-318 2021年7月  
  • 楯 真一, 錦見 恭子, 松岡 歩, 生水 真紀夫
    日本婦人科腫瘍学会雑誌 39(1) 307-307 2021年1月  
  • 竹原直希, 羽生裕二, 三橋暁, 太田昌幸, 池田純一郎, 松岡歩, 錦見恭子, 楯真一, 碓井宏和, 生水真紀夫
    日本婦人科腫瘍学会雑誌 39(1) 352-352 2021年  
  • 大渕 朝日, 楯 真一, 松岡 歩, 錦見 恭子, 羽生 裕二, 碓井 宏和, 三橋 暁, 生水 真紀夫
    関東連合産科婦人科学会誌 57(4) 615-621 2020年11月  
    原発性卵巣腫瘍と転移性卵巣腫瘍では治療法や予後が異なるため鑑別が重要であるが,術前診断に苦慮する.今回,多房性嚢胞性腫瘍を呈した転移性卵巣腫瘍を2例経験した.症例1:81歳女性.X年6月に肝内胆管癌(高分化腺癌,Stage II)の手術を受けた.術後化学療法中のX+1年4月下腹部膨隆感があり,両側卵巣に多房性嚢胞性腫瘍を指摘され,当科紹介となった.MRI検査で粘液性腺腫が疑われ,腹腔鏡補助下両側付属器切除術を施行した.術後病理診断は肝内胆管癌の卵巣転移であった.症例2:37歳女性.Y年3月に肝内胆管癌(中〜高分化型腺癌,Stage IV)の手術を受けた.術後化学療法後,経過観察されていた.Y+1年6月に下腹部痛のため近医を受診し,卵巣嚢腫を指摘され当科紹介となった.超音波検査で両側卵巣に多房性嚢胞性腫瘤を認め粘液性腺腫を疑った.子宮頸部細胞診でAGCを検出したため,頸部と内膜組織診を施行し高分化型腺癌を検出した.肝内胆管癌の転移を疑い,子宮全摘+両側付属器切除術を施行した.術後病理診断は肝内胆管癌の卵巣・子宮転移であった.今回の2例のように,肝内胆管癌の卵巣転移は多房性嚢胞性腫瘍を呈する可能性があるため,肝内胆管癌既往の多房性卵巣腫瘍症例では,再発や転移の可能性を念頭におく必要があると考えられた.(著者抄録)

共同研究・競争的資金等の研究課題

 2