武田 真人 (タケダ マヒト)

医学研究院 専門医学系部門 生殖・発達医学分野助教
北海道大学病院助教
Last Updated :2024/12/06

■研究者基本情報

学位

  • 博士(医学), 北海道大学

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■研究活動情報

論文

  • Distribution of Lymph Node Metastasis Sites in Endometrial Cancer Undergoing Systematic Pelvic and Para-Aortic Lymphadenectomy: A Proposal of Optimal Lymphadenectomy for Future Clinical Trials
    Tetsuji Odagiri, Hidemichi Watari, Tatsuya Kato, Takashi Mitamura, Masayoshi Hosaka, Satoko Sudo, Mahito Takeda, Noriko Kobayashi, Peixin Dong, Yukiharu Todo, Masataka Kudo, Noriaki Sakuragi
    ANNALS OF SURGICAL ONCOLOGY, 21, 8, 2755, 2761, SPRINGER, 2014年08月, [査読有り]
    英語, 研究論文(学術雑誌), The aim of this study was to demonstrate the precise mapping of lymph node metastasis (LNM) sites in endometrial cancer.A total of 266 patients who underwent primary radical surgery including systematic pelvic and para-aortic lymphadenectomy for endometrial cancer from 1993 to 2010 were enrolled in this study. We removed lymph nodes from the femoral ring to the para-aortic node up to the level of renal veins. We analyzed the distribution of positive-node sites according to their anatomical location.Overall, 42 of 266 patients (15.8 %) showed LNM. The median number of nodes harvested was 62.5 (range 40-119) in pelvic nodes (PLN), and 20 (range 3-47) in para-aortic nodes (PAN). Among 42 cases with positive-nodes, 16 cases (38.1 %) showed positive PLN alone, 7 cases (16.7 %) in PAN alone, and 19 cases (45.2 %) in both PLN and PAN. The most prevalent site of positive-nodes was PAN (9.8 %) followed by obturator nodes (9.4 %), internal iliac nodes (7.1 %), and common iliac nodes (5.6 %). Six of 19 cases (31.6 %) of positive PAN above the inferior mesenteric artery (IMA) showed negative PAN below IMA. Metastasis to the deep inguinal nodes was found to be extremely rare (0.38 %). Single-site LNM was the most frequently observed in obturator nodes, followed by PAN above IMA.Routine resection of deep inguinal nodes is not recommended, whereas para-aortic lymphadenectomy should be extended up to the level of renal veins for endometrial cancer.
  • Genital infection caused by Entamoeba histolytica confirmed by polymerase chain reaction analyses
    Hiroshi Asano, Masanori Kaneuchi, Itsuko Furuta, Yukie Yamaya, Kanako C. Hatanaka, Mahito Takeda, Yoshihiro Matsuno, Noriaki Sakuragi
    JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH, 40, 5, 1441, 1444, WILEY-BLACKWELL, 2014年05月, [査読有り]
    英語, 研究論文(学術雑誌), Entamoeba histolytica is estimated to infect approximately 1% of the global population. In Japan, the prevalence of amebic dysentery has been increasing, with more than 800 patients newly diagnosed annually. However, genital infection with E.histolytica is uncommon even in endemic areas. We present a case of vaginitis caused by E.histolytica. A 50-year-old Japanese woman without history of overseas travel presented to a nearby clinic with increased vaginal discharge. She had hemorrhagic erosion at the uterine cervix with yellowish vaginal discharge, and was referred to our hospital for exclusion of malignancy. Cervical cytology revealed periodic acid-Schiff-positive protozoa not aggregating around squamous cells, and thus amebic vaginitis was suspected. We performed polymerase chain reaction (PCR) analyses and identified E.histolytica. The vaginitis was treated with metronidazole, and the disappearance of amebic protozoa was confirmed by cytology and PCR. Therefore, it may be important to obtain early diagnosis by cervical cytology and PCR.
  • Impact of FDG PET in optimizing patient selection for cytoreductive surgery in recurrent ovarian cancer
    Yasuhiko Ebina, Hidemichi Watari, Masanori Kaneuchi, Mahito Takeda, Masayoshi Hosaka, Masataka Kudo, Hideto Yamada, Noriaki Sakuragi
    EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, 41, 3, 446, 451, SPRINGER, 2014年03月, [査読有り]
    英語, 研究論文(学術雑誌), Purpose To investigate the impact of PET and PET/CT scanning on decision-making in management planning and to identify the optimal setting for selecting candidates for surgery in suspicious recurrent ovarian cancer.
    Methods A retrospective chart review was performed in patients with possible recurrent ovarian cancer after primary optimal cytoreduction and taxane/carboplatin chemotherapy who had undergone FDG PET or FDG PET/CT scans from July 2002 to August 2008 to help make treatment decisions. The analysis included 44 patients who had undergone a total of 89 PET scans. The positive PET scans were classified as follows. (1) localized (one or two localized sites of FDG uptake), (2) multiple (three or more sites of FDG uptake), (3) diffuse (extensive low-grade activity outlining serosal and peritoneal surfaces).
    Results Of the 89 PET scans, 52 (58.4 %) led to a change in management plan. The total number of patients in whom cytoreductive surgery was selected as the treatment of choice increased from 12 to 35. Miliary disseminated disease, which was not detected by PET scan, was found in 22.2 % of those receiving surgery. Miliary disseminated disease was detected in 6 of the 12 patients with recurrent disease whose treatment-free interval (TFI) was <12 months, whereas none of those with a TFI of >= 12 months had such disease (P = 0.0031).
    Conclusion PET or PET/CT is useful for selecting candidates for cytoreductive surgery among patients with recurrent ovarian cancer. To avoid surgical attempts in those with miliary dissemination, patients with a TFI of >= 12 months are the best candidates for cytoreductive surgery.
  • Multivariate prognostic analysis of adenocarcinoma of the uterine cervix treated with radical hysterectomy and systematic lymphadenectomy
    Tatsuya Kato, Hidemichi Watari, Mahito Takeda, Masayoshi Hosaka, Takashi Mitamura, Noriko Kobayashi, Satoko Sudo, Masanori Kaneuchi, Masataka Kudo, Noriaki Sakuragi
    JOURNAL OF GYNECOLOGIC ONCOLOGY, 24, 3, 222, 228, KOREAN SOC GYNECOLOGY ONCOLOGY & COLPOSCOPY, 2013年07月, [査読有り]
    英語, 研究論文(学術雑誌), Objective: The aim of this study was to investigate the prognostic factors and treatment outcome of patients with adenocarcinoma of the uterine cervix who underwent radical hysterectomy with systematic lymphadenectomy.
    Methods: A total of 130 patients with stage IB to IIB cervical adenocarcinoma treated with hysterectomy and systematic lymphadenectomy from 1982 to 2005 were retrospectively analyzed. Clinicopathological data including age, stage, tumor size, the number of positive node sites, lymphovascular space invasion, parametrial invasion, deep stromal invasion (>2/3 thickness), corpus invasion, vaginal infiltration, and ovarian metastasis, adjuvant therapy, and survival were collected and Cox regression analysis was used to deteitnine independent prognostic factors.
    Results: An estimated five-year survival rate of stage IB1 was 96.6%, 75.0% in stage IB2, 100% in stage IIA, and 52.8% in stage IIB. Prognosis of patients with one positive-node site is similar to that of those with negative-node. Prognosis of patients with multiple positive-node sites was significantly poorer than that of negative and one positive-node site. Multivariate analysis revealed that lymph node metastasis, lymphovascular space invasion, and parametrial invasion were independent prognostic factors for cervical adenocarcinoma. Survival of patients with cervical adenocarcinoma was stratified into three groups by the combination of three independent prognostic factors.
    Conclusion: Lymph node metastasis, lymphovascular space invasion, and parametrial invasion were shown to be independent prognostic factors for cervical adenocarcinoma treated with hysterectomy and systematic lymphadenectomy.
  • New revised FIGO 2008 staging system for endometrial cancer produces better discrimination in survival compared with the 1988 staging system
    Tatsuya Kato, Hidemichi Watari, Daisuke Endo, Takashi Mitamura, Tetsuji Odagiri, Yousuke Konno, Masayoshi Hosaka, Noriko Kobayashi, Yukiharu Todo, Satoko Sudo, Mahito Takeda, Peixin Dong, Masanori Kaneuchi, Masataka Kudo, Noriaki Sakuragi
    JOURNAL OF SURGICAL ONCOLOGY, 106, 8, 938, 941, WILEY, 2012年12月, [査読有り]
    英語, 研究論文(学術雑誌), Background and Objectives The aim of this study was to analyze the stage migration and survival of endometrial cancer by the revised FIGO 2008 staging system compared with the 1988 staging system. Methods A total of 355 patients with endometrial cancer, who underwent complete surgical staging, were enrolled. We compared the surgical stages and survival by FIGO 1988 staging system with those by FIGO 2008 staging system. Results 2008 FIGO staging system resulted in an increase of stage I patients and decrease of stage II and IIIa patients. The 5-year overall survival (OS) rates for patients with 2008 FIGO stage IA and IB disease were 98.2% and 91.9%, respectively (P?=?0.004). Five-year OS rate of new stage II (82.6%) was significantly worse than that of new stage IA (98.2%, P?=?0.003). Patients with positive washing cytology alone revealed a 5-year OS rate similar to that of patients with new stage IIIA disease (96.2% vs. 90.9%, respectively; P?=?0.53). The 5-year OS rate for patients with stage IIIC1 disease was improved compared with that for patients with stage IIIC2 disease (85.7% vs. 63.0%, respectively; P?=?0.08). Conclusion New revised FIGO 2008 staging system for endometrial cancer produced better discrimination in OS outcomes compared with the 1988 system. J. Surg. Oncol. 2012; 106: 938941. (c) 2012 Wiley Periodicals, Inc.
  • Incidence of metastasis in circumflex iliac nodes distal to the external iliac nodes in intermediate- and high-risk endometrial cancer
    Yukiharu Todo, Hidenori Kato, Kazuhira Okamoto, Shinichiro Minobe, Yoshihiro Suzuki, Yoko Ohba, Mahito Takeda, Hidemichi Watari, Masanori Kaneuchi, Noriaki Sakuragi
    GYNECOLOGIC ONCOLOGY, 122, 1, 55, 58, ACADEMIC PRESS INC ELSEVIER SCIENCE, 2011年07月, [査読有り]
    英語, 研究論文(学術雑誌), Objective. The aim of this study was to elucidate the incidence of metastasis in circumflex iliac nodes distal to the external iliac nodes (CINDEIN), which are also called suprainguinal nodes, in intermediate- and high-risk endometrial cancer. Removal of these nodes needs to be discussed from the viewpoint of patient's quality of life because removal of CINDEIN is strongly related to lower extremity lymphedema.
    Methods. A retrospective chart review was carried out for 508 patients with intermediate- and high-risk endometrial cancer who were included in this study. We identified patients with lymph node metastasis. Lymph node sites were classified into four groups: (1) CINDEIN, (2) external iliac nodes, (3) Group A consisting of circumflex iliac nodes to the distal obturator nodes, internal iliac nodes, obturator nodes, cardinal ligament nodes (including deep obturator nodes), and sacral nodes, and (4) Group B consisting of common iliac nodes and para-aortic nodes. Logistic regression analysis was used to select risk factors for CINDEIN metastasis.
    Results. In an analysis of 508 patients with intermediate- and high-risk disease, CINDEIN metastasis was found in fourteen (2.8%) of the patients. Multivariate analysis confirmed that high-risk histology (OR = 5.7, 95% CI = 1.2-16.1) and Group A node metastasis (OR = 9.7, 95% CI = 2.9-31.4) were independent risk factors for CINDEIN metastasis. None of the patients with G1 endometrioid adenocarcinoma had CINDEIN metastasis. Three (2.5%) of the patients with G2 endometrioid adenocarcinoma had CINDEIN metastasis and all of these three patients had other pelvic node metastasis.
    Conclusion. Removal of CINDEIN can be eliminated in patients with G1 endometrial cancer and patients with G2 endometrial cancer who have no pelvic node metastasis. (C) 2011 Elsevier Inc. All rights reserved.
  • Risk factors for lower-limb lymphedema after surgery for cervical cancer
    Yoko Ohba, Yukiharu Todo, Noriko Kobayashi, Masanori Kaneuchi, Hidemichi Watari, Mahito Takeda, Satoko Sudo, Masataka Kudo, Hidenori Kato, Noriaki Sakuragi
    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY, 16, 3, 238, 243, SPRINGER TOKYO, 2011年06月, [査読有り]
    英語, 研究論文(学術雑誌), Lower-limb lymphedema (LLL) is a prevalent complication that is encountered after treatment for gynecological malignancies. The aim of this study was to evaluate the risk factors for postoperative LLL in patients with cervical cancer.
    We conducted a retrospective chart review for patients who had undergone surgery, including systematic lymphadenectomy, for cervical cancer. Patients who died of cancer, were evaluated for short periods of time (< 2 years), had missing medical records, or were suffering from deep venous thrombosis were excluded. We utilized the International Society of Lymphology staging of lymphedema severity as the diagnostic criteria for LLL, and patients with stage II or III lymphedema, as objectively determined by physicians, were included in the group of patients with LLL. Multivariate analysis was performed to confirm independent risk factors.
    A total of 155 patients with cervical cancer were evaluated. Thirty-one patients (20.0%) contracted LLL with a median follow-up of 6.1 years. Suprafemoral node dissection (odds ratio, 9.5; 95% confidence interval, 1.2-73.3; P = 0.031) and adjuvant radiotherapy (3.7; 1.2-10.9; P = 0.019) were identified as independent risk factors.
    Given that the effectiveness of the above two therapeutic options for cervical cancer is currently controversial, the clinical benefits of these therapies should be reevaluated specifically to conserve the quality of life for patients with this disease.
  • Initial failure site according to primary treatment with or without para-aortic lymphadenectomy in endometrial cancer
    Yukiharu Todo, Hidenori Kato, Shinichiro Minobe, Kazuhira Okamoto, Yoshihiro Suzuki, Satoko Sudo, Mahito Takeda, Hidemichi Watari, Masanori Kaneuchi, Noriaki Sakuragi
    GYNECOLOGIC ONCOLOGY, 121, 2, 314, 318, ACADEMIC PRESS INC ELSEVIER SCIENCE, 2011年05月, [査読有り]
    英語, 研究論文(学術雑誌), Objective. The objective of this study was to compare the initial failure sites in patients with endometrial cancer who underwent surgical treatment including pelvic lymphadenectomy with or without para-aortic lymphadenectomy.
    Methods. A retrospective chart review was carried out for 657 endometrial cancer patients with no residual disease after initial treatments including lymphadenectomy at two tertiary centers between 1987 and 2004. Surgical treatment at one institute included pelvic lymphadenectomy (PLX) without para-aortic lymphadenectomy (PALX), while surgical treatment including PLX + PALX was routinely performed at the other institute. We identified patients with recurrence and evaluated initial failure sites. Rates of recurrence in the respective sites were compared according to the type of lymphadenectomy.
    Results. Of the 657 patients, 103 (15.7%) suffered recurrence. There was no significant difference between the rate of intrapelvic recurrence in the PLX alone group and that in the PLX + PALX group (4.7% vs. 2.9%, p = 0.22). The rate of extrapelvic recurrence in the PLX alone group was significantly higher than that in the PLX + PALX group (16.1% vs. 6.2%, p < 0.0001), and the rate of para-aortic node (PAN) recurrence in the PLX alone group was also significantly higher than that in the PLX + PALX group (5.1% vs. 0.6%, p = 0.0004). In the analysis of patients who received adjuvant chemotherapy, the rate of PAN recurrence in the PLX alone group was significantly higher than that in the PLX + PALX group (9.5% vs. 1.3%, p = 0.0036).
    Conclusion. PAN recurrence was a failure pattern peculiar to the PLX alone group. Adjuvant chemotherapy might not be able to replace surgical removal as a treatment for metastatic lymph nodes. (C) 2011 Elsevier Inc. All rights reserved.
  • A validation study of the new revised FIGO staging system to estimate prognosis for patients with stage IIIC endometrial cancer
    Yukiharu Todo, Hidenori Kato, Shinichiro Minobe, Kazuhira Okamoto, Yoshihiro Suzuki, Yosuke Konno, Mahito Takeda, Hidemichi Watari, Masanori Kaneuchi, Noriaki Sakuragi
    GYNECOLOGIC ONCOLOGY, 121, 1, 126, 130, ACADEMIC PRESS INC ELSEVIER SCIENCE, 2011年04月, [査読有り]
    英語, 研究論文(学術雑誌), Objective. The aim of this study was to validate the role of the new FIGO staging system for estimating prognosis for patients with stage IIIC endometrial cancer.
    Methods. A total of 93 cases with stage IIIC were entered in this study and classified into three groups: one group of patients who underwent pelvic lymphadenectomy (PLX) and para-aortic lymphadenectomy (PALX) and who were for positive for pelvic node metastasis (PLNM) and negative for para-aortic node metastasis (PANM) (Group 1), one group of patients who underwent PLX alone and were positive for PLNM (Group 2) and one group of patients who underwent PLX and PALX and were positive for PANM (Group 3). Information on clinicopathologic findings and treatments was obtained from medical charts. Cox regression analysis was used to select prognostic factors.
    Results. The 5-years survival rates were 89.3% in Group 1, 46.5% in Group 2 and 59.9% in Group 3. The overall survival rate in Group 1 was significantly better than that in Group 2 (p = 0.0001) and Group 3 (p = 0.0016). No significant difference in overall survival was found between Group 2 and Group 3. Age, number of metastatic lymph nodes, type of lymphadenectomy and type of adjuvant therapy were significantly and independently related to overall survival. Only when patients received PALX, PANM was a prognostic risk factor.
    Conclusion. Sub-classification of stage IIIC would be functional for estimating prognosis in the revised FIGO staging system. Systematic lymphadenectomy including PALX has therapeutic significance for patients with stage IIIC endometrial cancer. Prognosis of patients with stage IIIC endometrial cancer would depend much more on application of lymphadenectomy including PALX than nodal status. (C) 2010 Elsevier Inc. All rights reserved.
  • Multivariate survival analysis of the patients with recurrent endometrial cancer
    Tetsuji Odagiri, Hidemichi Watari, Masayoshi Hosaka, Takashi Mitamura, Yousuke Konno, Tatsuya Kato, Noriko Kobayashi, Satoko Sudo, Mahito Takeda, Masanori Kaneuchi, Noriaki Sakuragi
    JOURNAL OF GYNECOLOGIC ONCOLOGY, 22, 1, 3, 8, KOREAN SOC GYNECOLOGY ONCOLOGY & COLPOSCOPY, 2011年03月, [査読有り]
    英語, 研究論文(学術雑誌), Objective: Few studies on the prognosticators of the patients with recurrent endometrial cancer after relapse have been reported in the literature. The aim of this study was to determine the prognosticators after relapse in patients with recurrent endometrial cancer who underwent primary complete cytoreductive surgery and adjuvant chemotherapy.Methods: Thirty-five patients with recurrent endometrial cancer were included in this retrospective analysis. The prognostic significance of several clinicopathological factors including histologic type, risk for recurrence, time to relapse after primary surgery, number of relapse sites, site of relapse, treatment modality, and complete resection of recurrent tumors were evaluated. Survival analyses were performed by Kaplan-Meier curves and the log-rank test. Independent prognostic factors were determined by multivariate Cox regression analysis.Results: Among the clinicopathological factors analyzed, histologic type (p=0.04), time to relapse after primary surgery (p=0.03), and the number of relapse sites (p=0.03) were significantly related to survival after relapse. Multivariate analysis revealed that time to relapse after primary surgery (hazard ratio, 6.8; p=0.004) and the number of relapse sites (hazard ratio, 11.1; p=0.002) were independent prognostic factors for survival after relapse. Survival after relapse could be stratified into three groups by the combination of two independent prognostic factors.Conclusion: We conclude that time to relapse after primary surgery, and the number of relapse sites were independent prognostic factors for survival after relapse in patients with recurrent endometrial cancer.
  • Survival and prognosticators of node-positive cervical cancer patients treated with radical hysterectomy and systematic lymphadenectomy
    Masayoshi Hosaka, Hidemichi Watari, Takashi Mitamura, Yousuke Konno, Tetsuji Odagiri, Tatsuya Kato, Mahito Takeda, Noriaki Sakuragi
    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY, 16, 1, 33, 38, SPRINGER TOKYO, 2011年02月, [査読有り]
    英語, 研究論文(学術雑誌), Lymph node metastasis (LNM) is known to be the most important prognostic factor in cervical cancer. We analyzed the number of positive lymph nodes and other clinicopathological factors as prognostic factors for survival in node-positive patients with cervical cancer.Node-positive cervical cancer patients (n = 108) who underwent radical hysterectomy and systematic lymphadenectomy in Hokkaido University Hospital from 1982 to 2002 were enrolled. Clinicopathological data including age, stage, histologic subtype, and the number of LNM sites were collected. The main outcome was the overall survival (OS) rate for Stage Ib-IIb patients treated with surgery and postoperative radiotherapy.The 5-year OS rate of patients with 1 positive node was 93.3%, that for 2 nodes was 77.3%, for 3 nodes it was 33.3%, and for 4 or more it was 13.8%. The OS rate of patients with 1 or 2 LNM sites was significantly better than that for patients with more than 2 LNM sites. The OS rate of patients with adenocarcinoma (Ad) (28.6%) was significantly lower than that for patients with other histologic subtypes (squamous cell carcinoma; 66.7%, adenosquamous carcinoma; 75.0%, p = 0.0003). Multivariate analysis revealed that > 2 LNM sites and Ad were independent prognostic factors for survival. The 5-year OS rate of patients with 1 or 2 LNM sites was 86.8%, a more favorable prognosis than the OS rates in other reports.More than two LNM sites and adenocarcinoma were independent prognostic factors for node-positive patients with cervical cancer.
  • A Retrospective Analysis of Postoperative Complications With or Without Para-aortic Lymphadenectomy in Endometrial Cancer
    Yosuke Konno, Yukiharu Todo, Shinichiro Minobe, Hidenori Kato, Kazuhira Okamoto, Satoko Sudo, Mahito Takeda, Hidemichi Watari, Masanori Kaneuchi, Noriaki Sakuragi
    INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER, 21, 2, 385, 390, LIPPINCOTT WILLIAMS & WILKINS, 2011年02月, [査読有り]
    英語, 研究論文(学術雑誌), Introduction: Although para-aortic lymphadenectomy (PALX) has not been accepted as a standard treatment for patients with endometrial cancer, it is possible that systematic lymphadenectomy including PALX has therapeutic significance for patients with intermediate-/high-risk endometrial cancer. On the other hand, a consensus regarding the safety of PALX has not been reached. The aim of this study was to compare the incidence rates of postoperative complications after pelvic lymphadenectomy (PLX) with or without PALX in patients with uterine corpus cancer.
    Methods: A retrospective chart review was carried out for all patients with endometrial cancer treated at 2 tertiary centers between 1998 and 2004. Surgery at one institute included both PLX and PALX, whereas PLX alone was routinely performed at the other institute. A total of 142 patients underwent PLX + PALX and 138 patients underwent PLX alone. We evaluated postoperative complications including intraoperative injury, ileus, lymphedema, lymphocyst, and thrombosis.
    Results: There was no fatal accident associated with surgery. Lymphedema was the most frequent complication. Comparing the PLX + PALX group and the PLX group, there were no significant differences in the rate of cases of lymphedema (23.2% vs 28.3%), lymphocyst (9.2% vs 9.4%), and thrombosis (4.9% vs 2.2%). The rate of cases of mild/moderate ileus in the PLX + PALX group was significantly higher than that in the PLX group (10.5% vs 2.9%; P = 0.011). However, no significant difference in the rates of cases of severe ileus was found between the 2 groups (1.4% vs 0.7%). There were also no significant differences between the 2 groups in the rates of intraoperative organ injury (2.8% vs 2.2%) and secondary operation for postoperative complications (4.9% vs 4.3%).
    Conclusions: Para-aortic lymphadenectomy can be performed with an acceptable morbidity under the conditions in which it is performed by experienced surgeons, and measures to prevent complications are properly taken.
  • Risk Factors for Persistent Low Bladder Compliance After Radical Hysterectomy
    Yasunari Oda, Yukiharu Todo, Sharon Hanley, Masayoshi Hosaka, Mahito Takeda, Hidemichi Watari, Masanori Kaneuchi, Masataka Kudo, Noriaki Sakuragi
    INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER, 21, 1, 167, 172, LIPPINCOTT WILLIAMS & WILKINS, 2011年01月, [査読有り]
    英語, 研究論文(学術雑誌), Introduction: Bladder compliance deteriorates immediately after radical hysterectomy (RH), and low bladder compliance causes upper urinary tract dysfunctions such as progressive hydronephrosis. The aims of this study were to clarify risk factors for persistent low bladder compliance after RH and to propose a postsurgical management protocol for improved recovery of bladder function.
    Methods: A total of 113 consecutive patients who underwent RH with the intention to preserve the pelvic autonomic nerve system were included in this prospective study. Urodynamic studies were performed according to a planned schedule: presurgery and 1, 3, 6, and 12 months after surgery. Autonomic nerves were preserved at least unilaterally in 95 (84.1%) of the 113 patients, but this was not possible in the remaining 18 patients (15.9%). Postoperative adjuvant radiation therapy (RT) was performed in 14 patients. The relationships between bladder compliance and various clinical factors were investigated using logistic regression analysis. Covariates included age, nerve-sparing procedure, adjuvant RT, and maximum abdominal pressure during the voiding phase. Bladder compliance at 12 months after surgery was used as the dependent variable.
    Results: Radical hysterectomy with a non-nerve-sparing procedure (odds ratio [OR], 3.4; 95% confidence interval [CI], 1.1-11.0), adjuvant RT (OR, 10.3; 95% CI, 2.5-43.5), and voiding with abdominal pressure at 3 months after surgery (OR, 2.9; 95% CI, 1.1-7.2) were risk factors for persistent low bladder compliance.
    Conclusions: A nerve-sparing procedure and prohibition of voiding with abdominal strain during the acute and subacute phases after RH resulted in improved recovery of bladder compliance. Adjuvant RT should be avoided in patients who undergo nerve-sparing RH if an alternative postoperative strategy is possible.
  • Survival effect of para-aortic lymphadenectomy in endometrial cancer (SEPAL study): a retrospective cohort analysis
    Yukiharu Todo, Hidenori Kato, Masanori Kaneuchi, Hidemichi Watari, Mahito Takeda, Noriaki Sakuragi
    LANCET, 375, 9721, 1165, 1172, ELSEVIER SCIENCE INC, 2010年04月, [査読有り]
    英語, 研究論文(学術雑誌), Background In response to findings that pelvic lymphadenectomy does not have any therapeutic benefit for endometrial cancer, we aimed to establish whether complete, systematic lymphadenectomy, including the para-aortic lymph nodes, should be part of surgical therapy for patients at intermediate and high risk of recurrence.
    Methods We selected 671 patients with endometrial carcinoma who had been treated with complete, systematic pelvic lymphadenectomy (n=325 patients) or combined pelvic and para-aortic lymphadenectomy (n=346) at two tertiary centres in Japan (January, 1986 June, 2004). Patients at intermediate or high risk of recurrence were offered adjuvant radiotherapy or chemotherapy. The primary outcome measure was overall survival.
    Findings Overall survival was significantly longer in the pelvic and para-aortic lymphadenectomy group than in the pelvic lymphadenectomy group (HR 0.53, 95% CI 0.38-0.76; p=0.0005). This association was also recorded in 407 patients at intermediate or high risk (p=0.0009), but overall survival was not related to lymphadenectorny type in low-risk patients. Multivariate analysis of prognostic factors showed that in patients with intermediate or high risk of recurrence, pelvic and para-aortic lymphadenectomy reduced the risk of death compared with pelvic lymphadenectomy (0.44, 0.30-0.64; p<0.0001). Analysis of 328 patients with intermediate or high risk who were treated with adjuvant radiotherapy or chemotherapy showed that patient survival improved with pelvic and para-aortic lymphadenectomy (0.48, 0.29-0.83; p=0.0049) and with adjuvant chemotherapy (0.59, 0.37-1.00; p=0.0465) independently of one another.
    Interpretation Combined pelvic and para-aortic lymphadenectomy is recommended as treatment for patients with endometrial carcinoma of intermediate or high risk of recurrence. If a prospective randomised or comparative cohort study is planned to validate the therapeutic effect of lymphadenectomy, it should include both pelvic and para-aortic lymphadenectomy in patients of intermediate or high risk of recurrence.
  • Survival and Failure Pattern of Patients With Endometrial Cancer After Extensive Surgery Including Systematic Pelvic and Para-Aortic Lymphadenectomy Followed by Adjuvant Chemotherapy
    Hidemichi Watari, Takashi Mitamura, Masashi Moriwaki, Masayoshi Hosaka, Yoko Ohba, Satoko Sudo, Yukiharu Todo, Mahito Takeda, Yasuhiko Ebina, Noriaki Sakuragi
    INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER, 19, 9, 1585, 1590, LIPPINCOTT WILLIAMS & WILKINS, 2009年12月, [査読有り]
    英語, 研究論文(学術雑誌), We investigated the survival and the failure pattern of 288 patients with endometrial cancer treated with extensive surgery including systematic pelvic and para-aortic lymphadenectomy followed by cisplatin-based chemotherapy from 1982 to 2002. We correlated the failure pattern with various clinicopathologic factors to find the predictors of recurrence sites. The 5-year overall survival rates were 97.5% for stage I, 87.5% for stage II, 85.2% for stage III, and 12.5% for stage IV Notably, the 5-year survival rate was 76.5% for patients with stage IIIC disease. Among patients with a low risk (n = 92) for recurrence who received no adjuvant chemotherapy, 2 (2.2%) showed recurrent disease. Among those with intermediate (n 98) and high (n = 98) risks for recurrence who received adjuvant chemotherapy, 9 (9.2%) and 20 (20.4%) showed recurrent disease, respectively. The recurrence sites were described as follows: distant (n = 12), vaginal (n = 8), peritoneal (n = 7), pelvic (n = 2), and lymphatic (n = 2). Lymphatic failure was found beyond the area of lymphadenectomy. Architectural and nuclear grades; myometrial, lymph-vascular space, and cervical invasions; and lymph node metastasis were predictors of distant failure. Cervical invasion and lymph node metastasis were predictors of vaginal failure. For patients with stage I/II cancer, the architectural and nuclear grades were related to distant failure. Seven (63.6%) of 11 patients with a low or intermediate risk survived after relapse, whereas only 1 (4.8%) of 21 patients with a high risk survived after a recurrence. We conclude that we need to further test the efficacy of systemic adjuvant therapy using new chemotherapeutic regimens to prevent distant failure and to improve the survival of patients with endometrial cancer.
  • Intrathoracic injection of paclitaxel for a patient with stage IV serous ovarian cancer: a case report
    Takashi Mitamura, Masayoshi Hosaka, Mahito Takeda, Hidemichi Watari, Noriaki Sakuragi
    CANCER CHEMOTHERAPY AND PHARMACOLOGY, 64, 1, 169, 170, SPRINGER, 2009年06月, [査読有り]
    英語, 研究論文(学術雑誌), There have so far only been few reports on the intrathoracic injection (IT) of paclitaxel for ovarian cancer.The patient was treated with IT paclitaxel to control a large volume of pleural effusion as neoadjuvant chemotherapy. A total of 220 mg (110 mg in each thoracic cavity) of paclitaxel was administrated and the pleural effusion dramatically decreased. The intrathoracic concentration of paclitaxel was 1,524.0, 107.5, 8.1, 11.0 and 3.8 mu m/l at 0, 24, 48, 72 and 96 h, respectively. The plasma concentration was 0.05, 0.11, 0.07, 0.04 and 0.02 mu m/l, respectively.An extremely high concentration was maintained over 96 h and there was slight transition into general circulation following IT administration. IT paclitaxel might be effective in some patients with ovarian serous adenocarcinoma who have a refractory tumor in the thoracic cavity.
  • Treatment of cervical cancer with adjuvant chemotherapy versus adjuvant radiotherapy after radical hysterectomy and systematic lymphadenectomy
    Masayoshi Hosaka, Hidemichi Watari, Mahito Takeda, Masashi Moriwaki, Yoko Hara, Yukiharu Todo, Yasuhiko Ebina, Noriaki Sakuragi
    JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH, 34, 4, 552, 556, WILEY-BLACKWELL, 2008年08月, [査読有り]
    英語, 研究論文(学術雑誌), Aim: To compare the clinical efficacy focused on post-treatment morbidity between adjuvant chemotherapy (CT) and pelvic radiotherapy (RT) after radical hysterectomy for patients with cervical cancer.
    Methods: A total of 125 patients with cervical squamous cell carcinoma who underwent radical hysterectomy and pelvic lymphadenectomy at Hokkaido University Hospital between 1991 and 2002 were enrolled in the study for retrospective analysis. Seventy patients with recurrent risk factors, including deep stromal invasion, lymph vascular space invasion, parametrial invasion, lymph node metastasis (LNM), and bulky tumor (>= 4 cm), received adjuvant therapy; 42 were treated with RT, and 28 were treated with CT. Almost all patients with multiple LNM received RT. Analyses were also performed on a subgroup of 50 patients without multiple LNM (23 RT, 27 CT). Clinical efficacy of post-treatment morbidity and survival was evaluated.
    Results: Because there were more patients with multiple LNM in the RT group, we analyzed disease-free survival in 50 patients without multiple LNM. The 3-year disease-free survival rate was 82.6% with RT and 96.3% with CT (P = 0.16). Postoperative bowel obstruction was significantly more frequent in the RT group versus the CT (P = 0.007) and no-therapy (P = 0.0026) groups. Urinary disturbance was also more frequent in the RT group than in the CT (P = 0.0016) and no-therapy (P = 0.089) groups.
    Conclusion: CT has the equivalent therapeutic effect as RT with fewer postoperative complications for patients with intermediate risks. A prospective randomized trial is needed to compare CT combined with radical hysterectomy and pelvic lymphadenectomy to RT or chemoradiotherapy.
  • [Successful desensitization using cisplatin after carboplatin-associated hypersensitivity reactions in 3 cases with recurrent ovarian carcinoma].
    Hosaka M, Ebina Y, Moriwaki M, Hara Y, Araki N, Todo Y, Takeda M, Watari H, Sakuragi N
    Gan to kagaku ryoho. Cancer & chemotherapy, 34, 1505, 1508, 9, 2007年09月, [査読有り]
  • A validation study of a scoring system to estimate the risk of lymph node metastasis for patients with endometrial cancer for tailoring the indication of lymphadenectomy
    Yukiharu Todo, Kazuhira Okamoto, Masaru Hayashi, Shinichiro Minobe, Eiji Nomura, Hitoshi Hareyama, Mahito Takeda, Yasuhiko Ebina, Hidemichi Watari, Noriaki Sakuragi
    GYNECOLOGIC ONCOLOGY, 104, 3, 623, 628, ACADEMIC PRESS INC ELSEVIER SCIENCE, 2007年03月, [査読有り]
    英語, 研究論文(学術雑誌), Objetive. The aim of this study was to verify whether a preoperative scoring system to estimate the risk of lymph node metastasis (LNM) in endometrial carcinoma is clinically useful for tailoring the indication of lymphadenectomy.
    Study design. LNM score was set up using volume index, serum CA125 level, and tumor grade/histology, which were found to be independent risk factors for LNM in a pilot study. Based on the LNM score before a validation study was started, the estimated rates of LNM (para-aortic LNM) were 3.4% (0.0%) in a low risk group, 7.7% (5.8%) in an intermediate group, 44.4% (30.6%) in a high risk group and 70.0% (50.0%) in an extremely high risk group. The validation study was carried out using data for 211 patients with endometrial carcinoma for whom three risk factors were preoperatively confirmed. Logistic regression analysis was used to determine whether these factors remain valid. The actual rate of LNM was investigated according to the LNM score.
    Results. Volume index, serum CA125 level, and tumor grade/histology were found to be independent risk factors for LNM in the cohort of this study. The actual rates of LNM (para-aortic LNM) were 3.2% (1.0%) in the low risk group, 15.3% (11.9%) in the intermediate group, 30.2% (23.8%) in the high risk group and 78.6% (57.1%) in the extremely high risk group.
    Conclusion. The actual rate of LNM for each score was fairly consistent with the estimated rate of LNM. Para-aortic lymphadenectomy may not be necessary in cases of a low risk group. A large prospective multicenter clinical trial needs to be conducted to establish the clinical usefulness of our preoperative scoring system. (c) 2006 Elsevier Inc. All rights reserved.
  • Lymph-vascular space invasion and number of positive para-aortic node groups predict survival in node-positive patients with endometrial cancer
    H Watari, Y Todo, M Takeda, Y Ebina, R Yamamoto, N Sakuragi
    GYNECOLOGIC ONCOLOGY, 96, 3, 651, 657, ACADEMIC PRESS INC ELSEVIER SCIENCE, 2005年03月, [査読有り]
    英語, 研究論文(学術雑誌), Objective. The aim of this Study was to determine pathologic variables associated with disease-specific survival of node-positive patients with endometrial carcinoma treated with combination of surgery including pelvic and para-aortic lymphadenectomy and adjuvant chemotherapy.
    Methods. Survival of 55 node-positive endometrial carcinoma patients prospectively treated with Surgery and adjuvant chemotherapy between 1982 and 2002 at Hokkaido University Hospital was compared to various histopathologic variables. All patients underwent primary surgical treatment including pelvic and para-aortic lymphadenectomy followed by adjuvant chemotherapy consisting of intravenous cisplatin, doxorubicin, and cyclophosphamide. Survival analyses were performed by the Kaplan-Meier curves and the log-rank test. Independent prognostic factors were determined by multivariate Cox regression analysis using a forward stepwise selection.
    Results. Among 303 consecutive endometrial cancer patients treated during the period of this study, 55 patients (18.2%), including 44 without peritoneal rnetastasis (FIGO stage IIIc) and II with peritoneal metastasis (FIGO stage IV), were found to have retroperitoneal lymph node metastasis. Multivariate Cox regression analysis revealed that peritoneal metastasis and lymph-vascular space invasion (LVSI) were independently related to poor Survival in node-positive endometrial carcinoma. The estimated 5-year survival rate of stage IIIc patients with or without moderate/prominent LVSI was 50.9% and 93.3%, respectively with statistically significant difference (P = 0.0024). The estimated 5-year survival rate of stage IV patients was 20.0%. Prognosis of stage IIIc patients could be stratified into three groups by the number of positive para-aortic node (PAN) with an estimated 5-year survival rate of 86.4% for no positive PAN (n = 23), 60.4% for one positive PAN (n = 13), and 20.0% for >= 2 positive PAN (n = 8). The difference of survival rate between no or one positive PAN and >= 2 positive PAN was statistically significant (P = 0.0007 for no positive PAN vs. >= 2 positive PAN, P = 0.0319 for one positive PAN vs. >= 2 positive PAN). Multivariate analysis including number of positive PAN groups showed that LVSI, number of positive PAN groups were independent prognostic factors for survival. Survival of patients with stage IIIc disease could be stratified into three groups by combination of LVSI and number of positive PAN groups with an estimated 5-year Survival rate of 93.3% for no or one positive PAN group with nil or minimal LVSI, 62.6% for no or one positive PAN group with intermediate or prominent LVSI, and 20.0% for 2 positive PAN groups irrespective of LVSI (P = 0.0002 for no or one positive PAN group with nil or minimal LVSI vs. 2 positive PAN groups, P = 0.0223 for no or one positive PAN group with nil or minimal LVSI vs. no or one positive PAN group with intermediate or prominent LVSI, P = 0.0388 for no or one positive PAN group with intermediate or prominent LVSI vs. >= 2 positive PAN groups).
    Conclusions. LVSI and number of positive PAN groups were independent prognostic factors for stage IIIc endometrial cancer patients. Postoperative therapy and follow-up modality need to be individualized according to LVSI and the number of positive PAN for stage life patients. New molecular markers to predict the Prognosis of endometrial cancer patients preoperatively should be found for individualization of treatment. New chemotherapy regimen including taxane needs to be considered as an adjuvant therapy for patients with node-positive endometrial cancer. (c) 2004 Elsevier Inc. All rights reserved.
  • Lymphatic mapping and sentinel node identification as related to the primary sites of lymph node metastasis in early stage ovarian cancer
    H Negishi, M Takeda, T Fujimoto, Y Todo, Y Ebina, H Watari, R Yamamoto, H Minakami, N Sakuragi
    GYNECOLOGIC ONCOLOGY, 94, 1, 161, 166, ACADEMIC PRESS INC ELSEVIER SCIENCE, 2004年07月, [査読有り]
    英語, 研究論文(学術雑誌), Objective. We evaluated the primary sites of lymph node (LN) metastasis in patients during the early stage of ovarian cancer.
    Methods. Study 1: patients with clinical stage I and II common epithelial ovarian carcinoma (n=150) underwent systematic retroperitoneal LN dissection of the pelvic and paraaortic areas. The relationship between the incidence and location of LN metastasis and clinical and histological characteristics was examined. Study 2: we studied I I women with endometrial or fallopian tube tumors. At laparotomy, activated charcoal solution was injected into the unilateral cortex of the ovary. Ten minutes later, the retroperitoneal spaces were opened and charcoal uptake within the pelvic lymph node (PLN) and paraaortic node (PAN) as far as the level of renal vein was examined.
    Results. Study 1: The incidence of LN metastasis by stage was 6.5% (8/123) in stage I and 40.7% (11/27) in stage II. Among 19 patients with LN metastasis, 14 had only PAN, 2 had only pelvic LN, and 3 had both PAN and PLN metastases. Metastasis was limited to the ipsilateral side in 12 (63%) patients, but was bilateral in 5 (26%) and contralateral to the neoplastic ovary in 2 (11%). Positive peritoneal cytology was significantly (P<0.05) correlated with lymph node metastasis. Study 2: Lymphatic channels along the ovarian vessels were identified in all injected ovaries. Charcoal was deposited in the LN of all patients. The locations of these nodes included PAN in all patients, common iliac node in three, and external iliac node in one.
    Conclusion. PAN is the primary site of LN metastasis in ovarian cancer. Bilateral PAN dissections are necessary to determine the extent of tumors even in stage I ovarian carcinoma. (C) 2004 Elsevier Inc. All rights reserved.
  • Cytological features of cervical smears in serous adenocarcinoma of the endometrium
    Y Todo, S Minobe, K Okamoto, M Takeda, Y Ebina, H Watari, M Terashima, M Kaneuchi, R Yamamoto, N Sakuragi
    JAPANESE JOURNAL OF CLINICAL ONCOLOGY, 33, 12, 636, 641, OXFORD UNIV PRESS, 2003年12月, [査読有り]
    英語, 研究論文(学術雑誌), Objective: Serous adenocarcinoma (SAC) of the endometrium has a poor prognosis compared with that of typical endometrioid adenocarcinoma (EAC). The objective of this study was to determine whether SAC can be distinguished from EAC preoperatively by cervical or endometrial cytology.
    Study design: Cervical smears and endometrial smears obtained from 128 patients with endometrial carcinoma were reviewed. Histological types included 117 cases of EAC and 11 cases of SAC. The positive rates of cervical smears and those of endometrial smears in SAC and EAC cases were compared. Papillary clusters and bare nuclei of malignant cells in positive cervical smears were also investigated for their diagnostic significance in discriminating between EAC and SAC.
    Results: The positive rate of cervical smears in SAC was significantly higher than that in EAC (72.7 vs 27.4%, P < 0.05). Among cases with positive cervical smears, there were significantly more cases with papillary clusters and/or bare nuclei in cases of SAC than in cases of EAC.
    Conclusion: When endometrial carcinoma is clinically suspected and a cervical smear is positive, the predominance of either papillary clusters or features of bare nuclei of malignant cells in the smear may indicate the presence of SAC.
  • Multivariate analysis of histopathologic prognostic factors for invasive cervical cancer treated with radical hysterectomy and systematic retroperitoneal lymphadenectomy
    N Takeda, N Sakuragi, M Takeda, K Okamoto, M Kuwabara, H Negishi, M Oikawa, R Yamamoto, H Yamada, S Fujimoto
    ACTA OBSTETRICIA ET GYNECOLOGICA SCANDINAVICA, 81, 12, 1144, 1151, BLACKWELL MUNKSGAARD, 2002年12月, [査読有り]
    英語, 研究論文(学術雑誌), Background. The aim of this study was to identify the independent histopathologic prognostic factors for patients with cervical carcinoma treated with radical hysterectomy including paraaortic lymphadenectomy.
    Methods. A total of 187 patients with stage IB to IIB cervical carcinomas treated with radical hysterectomy and systematic retroperitoneal lymphadenectomy were retrospectively analyzed. The median follow-up period was 83 months. Cox regression analysis was used to select independent prognostic factors.
    Results. Using multivariate Cox regression analysis, lymph node (LN) status (negative vs. metastasis to pelvic nodes except for common iliac nodes vs. common iliac/paraaortic node metastasis), histopathologic parametrial invasion, lymph-vascular space invasion (LVSI), and histology of pure adenocarcinoma were found to be independently related to patients' poor survival. For patients who had a tumor histologically confined to the uterus and have neither parametrial invasion nor lymph node metastasis, LVSI was the most important prognostic factor, and histologic type, depth of cervical stromal invasion, and tumor size were not related to survival. The survival of patients with a tumor extending to parametrium or pelvic lymph node(s) was adversely affected by histology of pure adenocarcinoma. When the tumor extended to common iliac or paraaortic nodes, patients' survival became quite poor irrespective of LVSI or histologic type of pure adenocarcinoma. Patients' prognosis could be stratified into low risk (patients with a tumor confined to the uterus not associated with LVSI: n = 80), intermediate risk (patients with a tumor confined to the uterus associated with positive LVSI, and patients with squamous/adenosquamous carcinoma associated with pelvic lymph node metastasis or parametrial invasion: n = 86), and high risk (patients with pure adenocarcinoma associated with pelvic lymph node metastasis or parametrial invasion, and patients with common iliac/paraaortic node metastasis: n = 21) with an estimated 5-year survival rate of 100 +/- 0 (mean +/- SE)%, 85.5 +/- 3.9%, and 25.1 +/- 9.7%, respectively.
    Conclusions. LN status, parametrial invasion, LVSI, and histology of pure adenocarcinoma are important histopathologic prognostic factors of cervical carcinoma treated with radical hysterectomy and systematic retroperitoneal lymphadenectomy. Prognosis for patients with cervical carcinoma may be stratified by combined analysis of these histopathologic prognostic factors. Postoperative therapy needs to be individualized according to these prognostic factors and validated for its efficacy using randomized clinical trials.
  • Clinical trial and pharmacokinetic study of combination paclitaxel and carboplatin in patients with epithelial ovarian cancer
    R Yamamoto, M Kaneuchi, M Nishiya, Y Todo, M Takeda, K Okamoto, H Negishi, N Sakuragi, S Fujimoto, T Hirano
    CANCER CHEMOTHERAPY AND PHARMACOLOGY, 50, 2, 137, 142, SPRINGER-VERLAG, 2002年08月, [査読有り]
    英語, 研究論文(学術雑誌), Purpose: To determine the recommended dose of paclitaxel in chemotherapy used in combination with carboplatin, and to examine the pharmacokinetic parameters of paclitaxel and carboplatin in Japanese patients with epithelial ovarian cancer. Methods: The study group comprised 18 patients (median age 53 years, range 30-67 years) who received a total of 28 courses of first-line chemotherapy. The paclitaxel levels were set at 150 mg/m(2) (n = 5), 175 mg/m(2) (n = 6) and 200 mg/m(2) (n = 7), with the fixed dose of carboplatin at AUC 5. The plasma concentrations of paclitaxel in 28 courses and platinum in 23 courses were measured to determine the in vivo pharmacokinetics parameters. Results: The nadir of neutrophils in the paclitaxel 200 mg/m(2) group was significantly lower (P < 0.05) than in the 150 and 175 mg/m(2) groups. Of seven patients in the paclitaxel 200 mg/m(2) group, one had grade 3 myalgia, another grade 3 neuropathy, and two grade 4 neutropenia. Paclitaxel AUC and the peak level tended to be dose-dependent, clearly indicating a two-phase disappearance. Further, the paclitaxel dosage and paclitaxel AUC were also dose-dependent. Using a limited sampling protocol for carboplatin, the carboplatin AUC was found to change little in relation to the paclitaxel dosage. Conclusions: Based on the results of this clinical trial and pharmacokinetic study, 175 mg/m(2) of paclitaxel as a 3-h infusion in combination with carboplatin AUC 5 can be considered as the recommended dose for Japanese ovarian cancer patients.
  • Preoperative serum SCC, CA125, and CA19-9 levels and lymph node status in squamous cell carcinoma of the uterine cervix
    M Takeda, N Sakuragi, K Okamoto, Y Todo, SI Minobe, E Nomura, H Negishi, M Oikawa, R Yamamoto, S Fujimoto
    ACTA OBSTETRICIA ET GYNECOLOGICA SCANDINAVICA, 81, 5, 451, 457, BLACKWELL MUNKSGAARD, 2002年05月, [査読有り]
    英語, 研究論文(学術雑誌), Background. We wanted to investigate the clinical usefulness of determining the pretreatment levels of multiple serum tumor markers in predicting lymph node status and the prognosis for patients with cervical carcinoma.
    Methods. The preoperative serum levels of squamous cell carcinoma antigen (SCC), cancer antigens CA125 and CA19-9 were assayed simultaneously in 103 patients with stages IB to IIB cervical SCC undergoing radical hysterectomy. The cut-off values of SCC, CA125, and CA19-9 in this study were 1.5 ng/ml, 35 U/ml, and 37 U/ml, respectively. The relation between preoperative tumor marker levels and histopathologic prognostic factors including lymph node metastasis and patient survival was studied.
    Results. Preoperative serum SCC, CA125, and CA19-9 levels were significantly related to the FIGO stage. In addition, serum SCC and CA125 levels were significantly related to tumor diameter, depth of cervical stromal invasion, lymph-vascular space invasion, and lymph node metastasis. We subsequently created a double-tumor-marker (DTM) index, which incorporated the number of positive markers of SCC and CA125. The DTM index was strongly related to the number of positive pelvic lymph nodes (p=0.0002) and to the site of positive nodes (none vs. pelvic only vs. common iliac/paraaortic) (p=0.0005). Probability of lymph node metastasis according to the DTM index=0, 1, and 2 was 6/48 (12.5%), 14/45 (31.1%), and 8/10 (80.0%), respectively. The rate of common iliac/paraaortic node metastasis according to the DTM index=0, 1, and 2 was 1148 (2.1%), 2/45 (4.4%), and 3110 (30.0%), respectively. By logistic regression analysis, it was shown that the DTM index and tumor diameter were independently related to lymph node metastasis. Using multivariate Cox regression analysis including singly determined serum SCC and CA125 levels, clinical stage (IB/IIA vs. IIB), tumor diameter (less than or equal to2 vs. 2-4 vs. >4cm), parametrial invasion, lymph node metastasis, and the DTM index, the DTM index was found to be the most important prognostic factor (p=0.0005). However, when the sites of positive nodes were included in the multivariate analysis, only the sites of positive nodes (p=0.0008) and parametrial invasion (p=0.041) showed independent prognostic significance.
    Conclusion. Combination assay of pretreatment serum SCC and CA125 levels seems to be useful in estimating lymph node status and the prognosis for patients with cervical SCC in a preoperative setting.
  • Para-aortic lymph node metastasis in relation to serum CA 125 levels and nuclear grade in endometrial carcinoma
    Y Ebina, N Sakuragi, H Hareyama, Y Todd, E Nomura, M Takeda, K Okamoto, H Yamada, R Yamamoto, S Fujimoto
    ACTA OBSTETRICIA ET GYNECOLOGICA SCANDINAVICA, 81, 5, 458, 465, BLACKWELL MUNKSGAARD, 2002年05月, [査読有り]
    英語, 研究論文(学術雑誌), Background. To investigate the relationship between preoperative serum CA 125 levels and para-aortic lymph node (PAN) metastasis as determined by systematic pelvic and para-aortic lymph node dissection in endometrial carcinoma.
    Methods. This study included 180 patients (n = 55, premenopausal; n = 125, postmenopausal) with endometrial carcinoma treated by complete surgical staging. Cut-off values of preoperative serum CA 125 levels for PAN metastasis were determined by receiver characteristic curve (ROC) analysis. Logistic regression analysis was used to determine independent predictors for PAN metastasis.
    Results. The median serum CA 125 levels of patients with PAN metastasis were significantly higher than the levels of those with no metastasis in both premenopausal and postmenopausal groups. Based on ROC analysis, we could determine four cut-off values (70 and 210 U/mL for premenopausal patients, 20 and 60 U/mL for postmenopausal patients) and categorize the serum CA 125 levels into low, moderate and high groups. By logistic regression analysis, the CA 125 level and nuclear grade were found to be significant predictors of PAN metastasis, respectively. Using this model, the patients were stratified into three risk groups. The probabilities of PAN metastasis for patients in the low-risk, intermediate-risk and high-risk groups were less than 2%, 2-25% and more than 50%, respectively.
    Conclusions. Serum CA 125 levels and nuclear grade are important risk factors for PAN metastasis in endometrial carcinoma.
  • Comparison of the results of radical hysterectomy: Sequential observations in each period
    Y Kobamatsu, R Yamamoto, M Kaneuchi, T Mitamura, S Minobe, Y Todo, M Takeda, K Okamoto, E Nomura, H Negishi, N Sakuragi, S Fujimoto
    JAPANESE JOURNAL OF CLINICAL ONCOLOGY, 32, 3, 103, 107, OXFORD UNIV PRESS, 2002年03月, [査読有り]
    英語, 研究論文(学術雑誌), Background: The efficacy of drains and of antibiotics for prophylaxis of postoperative retroperitoneal infections following radical hysterectomy with systematic lymphadenectomy has not yet been adequately investigated.
    Methods: Patients who had just undergone radical hysterectomy were divided into three groups. We used a retroperitoneal drain transvaginally for Groups A (n = 54) and B (n = 55) and transabdominally for Group C (n = 103). Group A was administered a first- and Groups B and C a second- or third-generation cephem antibiotic as the prophylactic antibiotic. We compared the surgery time, blood loss, fever index and febrile morbidity in these three groups.
    Results: The average surgery time was Group A 344.2 +/- 13.7 min (mean SE), Group B 425.6 +/- 11.0 min and Group C 528.2 +/- 10.9 min. A significant difference was observed among the groups (p < 0.05). In terms of blood loss during surgery, a significant increase (p < 0.05) occurred in Groups B (2400 196 g) and C (2373 130 g) compared with Group A (1820 122 g). For fever index, Group A showed a value of 36.1 +/- 2.7 dh, Group B 19.9 +/- 2.4 dh and Group C 8.8 +/- 1.5 dh. A significant difference was observed among the groups (p < 0.01). In terms of febrile morbidity, significant differences (p < 0.01, p < 0.0001) were observed between Groups B (14.6%) and C (8.7%) in comparison with Group A (44.4%), respectively.
    Conclusion: In radical hysterectomy with systematic lymphadenectomy, it may be preferable to choose transabdominal drains in the retroperitoneal space and second-generation cephem antibiotics for prophylaxis of postoperative retroperitoneal infections.
  • Papillary squamous cell carcinoma of the uterine cervix: a report of two cases with human papillomavirus 16 DNA
    T Fujimoto, N Sakuragi, M Shimizu, H Watari, M Takeda, K Okamoto, E Nomura, R Yamamoto, K Okuyama, S Fujimoto
    ACTA OBSTETRICIA ET GYNECOLOGICA SCANDINAVICA, 81, 2, 176, 178, BLACKWELL MUNKSGAARD, 2002年02月, [査読有り]
    英語, 研究論文(学術雑誌)

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