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 대한부인종양학회 2013 Journal of Gynecologic Oncology Vol.24 No.3

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 determine 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.

Incidence of gastrointestinal perforation associated with bevacizumab in combination with neoadjuvant chemotherapy as first- line treatment of advanced ovarian, fallopian tube, or peritoneal cancer: analysis of a Japanese healthcare claims database

Akihiko Ueda,Hidemichi Watari,Masaki Mandai,Shunichi Fukuhara,Yasuo Sugitani,Kiyoko Ogino,Shuichi Kamijima,Takayuki Enomoto 대한부인종양학회 2022 Journal of Gynecologic Oncology Vol.33 No.6

Objective: To assess the incidence of bevacizumab-associated gastrointestinal (GI) perforation during first-line treatment of patients with ovarian, fallopian tube, or peritoneal cancer receiving neoadjuvant chemotherapy (NAC) in Japanese real-world clinical practice. Methods: A retrospective study was conducted using a healthcare claims database owned by Medical Data Vision Co., Ltd. (study period, 2008–2020). Patients who initiated first-line treatment of ovarian, fallopian tube, or peritoneal cancer were identified and divided into NAC and primary debulking surgery (PDS) groups. The incidence of bevacizumab-associated GI perforation was compared within the NAC group and between the groups. Results: Paclitaxel + carboplatin (TC) was most commonly used as first-line treatment (39.5% and 59.6% in the NAC and PDS groups, respectively). TC + bevacizumab was used in 9.3% and 11.6% of patients in the NAC and PDS groups, respectively. In the NAC group receiving TC, the proportion of patients with risk factors for GI perforation was lower among patients with versus without concomitant bevacizumab. The incidence of GI perforation in the NAC group was 0.38% (1/266 patients) in patients receiving TC + bevacizumab and 0.18% (2/1,131 patients) in patients receiving TC without bevacizumab (risk ratio=2.13; 95% confidence interval [CI]=0.19 to 23.36; risk difference=0.20; 95% CI=−0.58 to 0.97). None of the 319 patients in the PDS group receiving TC + bevacizumab had GI perforation.

Additive effect of rikkunshito, an herbal medicine, on chemotherapy-induced nausea, vomiting, and anorexia in uterine cervical or corpus cancer patients treated with cisplatin and paclitaxel: results of a randomized phase II study (JORTC KMP-02)

Shunsuke Ohnishi,Hidemichi Watari,Maki Kanno,Yoko Ohba,Satoshi Takeuchi,Tempei Miyaji,Shunsuke Oyamada,Eiji Nomura,Hidenori Kato,Toru Sugiyama,Masahiro Asaka,Noriaki Sakuragi,Takuhiro Yamaguchi,Yasuhi 대한부인종양학회 2017 Journal of Gynecologic Oncology Vol.28 No.5

Objective: Rikkunshito, an herbal medicine, is widely prescribed in Japan for the treatmentof anorexia and functional dyspepsia, and has been reported to recover reductions in foodintake caused by cisplatin. We investigated whether rikkunshito could improve chemotherapyinducednausea and vomiting (CINV) and anorexia in patients treated with cisplatin. Methods: Patients with uterine cervical or corpus cancer who were to receive cisplatin (50 mg/m2day 1) and paclitaxel (135 mg/m2day 0) as first-line chemotherapy were randomly assignedto the rikkunshito group receiving oral administration on days 0–13 with standard antiemetics,or the control group receiving antiemetics only. The primary endpoint was the rate of completecontrol (CC: no emesis, no rescue medication, and no significant nausea) in the overall phase(0–120 hours). Two-tailed p<0.20 was considered significant in the planned analysis. Results: The CC rate in the overall phase was significantly higher in the rikkunshito groupthan in the control group (57.9% vs. 35.3%, p=0.175), as were the secondary endpoints:the CC rate in the delayed phase (24–120 hours), and the complete response (CR) rates(no emesis and no rescue medication) in the overall and delayed phases (63.2% vs. 35.3%, p=0.095; 84.2% vs. 52.9%, p=0.042; 84.2% vs. 52.9%, p=0.042, respectively), and time totreatment failure (p=0.059). Appetite assessed by visual analogue scale (VAS) appeared to besuperior in the rikkunshito group from day 2 through day 6. Conclusion: Rikkunshito provided additive effect for the prevention of CINV and anorexia

Lymphadenectomy can be omitted for low-risk endometrial cancer based on preoperative assessments

Takashi Mitamura,Hidemichi Watari,Yukiharu Todo,Tatsuya Kato,Yosuke Konno,Masayoshi Hosaka,Noriaki Sakuragi 대한부인종양학회 2014 Journal of Gynecologic Oncology Vol.25 No.4

Objective: According to the International Federation of Gynecology and Obstetrics staging, some surgeons perform lymphadenectomy in all patients with early stage endometrial cancer to enable the accurate staging. However, there are some risks to lymphadenectomy such as lower limb lymphedema. The aim of this study was to investigate whether preoperative assessment is useful to select the patients in whom lymphadenectomy can be safely omitted. Methods: We evaluated the risk of lymph node metastasis (LNM) using LNM score (histological grade, tumor volume measured in magnetic resonance imaging [MRI], and serum CA-125), myometrial invasion and extrautrerine spread assessed by MRI. Fifty-six patients of which LNM score was 0 and myometrial invasion was less than 50% were consecutively enrolled in the study in which a lymphadenectomy was initially intended not to perform. We analyzed several histological findings and investigated the recurrence rate and overall survival. Results: Fifty-one patients underwent surgery without lymphadenectomy. Five (8.9%) who had obvious myometrial invasion intraoperatively underwent systematic lymphadenectomy. One (1.8%) with endometrial cancer which was considered to arise from adenomyosis had para-aortic LNM. Negative predictive value of deep myometrial invasion was 96.4% (54/56). During the mean follow-up period of 55 months, one patient with deep myometrial invasion who refused an adjuvant therapy had tumor recurrence. The overall survival rate was 100% during the study period. Conclusion: This preoperative assessment is useful to select the early stage endometrial cancer patients without risk of LNM and to safely omit lymphadenectomy.

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 대한부인종양학회 2011 Journal of Gynecologic Oncology Vol.22 No.1

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. 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.

A multicenter comparative study of endoscopic ultrasound-guided fine-needle biopsy using a Franseen needle versus conventional endoscopic ultrasound-guided fine-needle aspiration to evaluate microsatellite instability in patients with unresectable pancre

Tadayuki Takagi,Mitsuru Sugimoto,Hidemichi Imamura,Yosuke Takahata,Yuki Nakajima,Rei Suzuki,Naoki Konno,Hiroyuki Asama,Yuki Sato,Hiroki Irie,Jun Nakamura,Mika Takasumi,Minami Hashimoto,Tsunetaka Kato 대한소화기내시경학회 2023 Clinical Endoscopy Vol.56 No.1

high tumors. Therefore, sufficient sampling of histological specimens is necessary in cases of unresectable pancreatic cancer (UR-PC). This multicenter study investigated the efficacy of endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) using a Franseen needlefor MSI evaluation in patients with UR-PC. Methods: A total of 89 patients with UR-PC who underwent endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) orEUS-FNB using 22-G needles at three hospitals in Japan (2018–2021) were enrolled. Fifty-six of these patients (FNB 23 and FNA 33)were followed up or evaluated for MSI. Patient characteristics, UR-PC data, and procedural outcomes were compared between patientswho underwent EUS-FNB and those who underwent EUS-FNA. Results: No significant difference in terms of sufficient tissue acquisition for histology was observed between patients who underwentEUS-FNB and those who underwent EUS-FNA. MSI evaluation was possible significantly more with tissue samples obtained usingEUS-FNB than with tissue samples obtained using EUS-FNA (82.6% [19/23] vs. 45.5% [15/33], respectively; p<0.01). In the multivariateanalysis, EUS-FNB was the only significant factor influencing the possibility of MSI evaluation. Conclusions: EUS-FNB using a Franseen needle is desirable for ensuring sufficient tissue acquisition for MSI evaluation.

Nerve-sparing radical hysterectomy in the precision surgery for cervical cancer

Noriaki Sakuragi,GenMurakami,Yosuke Konno,Masanori Kaneuchi,Hidemichi Watari 대한부인종양학회 2020 Journal of Gynecologic Oncology Vol.31 No.3

Precision cancer surgery is a system that integrates the accurate evaluation of tumor extension and aggressiveness, precise surgical maneuvers, prognosis evaluation, and prevention of the deterioration of quality of life (QoL). In this regard, nerve-sparing radical hysterectomy has a pivotal role in the personalized treatment of cervical cancer. Various types of radical hysterectomy can be combined with the nerve-sparing procedure. The extent of parametrium and vagina/paracolpium excision and the nerve-sparing procedure are tailored to the tumor status. Advanced magnetic resonance imaging technology will improve the assessment of the local tumor extension. Validated risk factors for perineural invasion might guide selecting treatment for cervical cancer. Type IV Kobayashi (modified Okabayashi) radical hysterectomy combined with the systematic nerve-sparing procedure aims to both maximize the therapeutic effect and minimize the QoL impairment. Regarding the technical aspect, the preservation of vesical nerve fibers is essential. Selective transection of uterine nerve fibers conserves the vesical nerve fibers as an essential piece of the pelvic nervous system comprising the hypogastric nerve, pelvic splanchnic nerves, and inferior hypogastric plexus. This method is anatomically and surgically valid for adequate removal of the parametrial and vagina/paracolpium tissues while preserving the total pelvic nervous system. Local recurrence after nerve-sparing surgery might occur due to perineural invasion or inadequate separation of pelvic nerves cutting through the wrong tissue plane between the pelvic nerves and parametrium/paracolpium. Postoperative management for long-term maintenance of bladder function is as critical as preserving the pelvic nerves.

Phase II study of niraparib in recurrent or persistent rare fraction of gynecologic malignancies with homologous recombination deficiency (JGOG2052)

Hiroshi Asano,Katsutoshi Oda,Kosuke Yoshihara,Yoichi M Ito,Noriomi Matsumura,Muneaki Shimada,Hidemichi Watari,Takayuki Enomoto 대한부인종양학회 2022 Journal of Gynecologic Oncology Vol.33 No.4

Background: Poly (adenosine diphosphate)-ribose polymerase (PARP) inhibitors for tumors with homologous recombination deficiency (HRD), including pathogenic mutationsin , have been developed. Genomic analysis revealed that about 20% of uterine leiomyosarcoma (uLMS) have HRD, including 7.5%–10% of alterations and 4%–6% of carcinomas of the uterine corpus, and 2.5%–4% of the uterine cervix have alterations of. Preclinical and clinical case reports suggest that PARP inhibitors may be effective against those targets. The Japanese Gynecologic Oncology Group (JGOG) is now planning to conduct a new investigator-initiated clinical trial, JGOG2052. Methods: JGOG2052 is a single-arm, open-label, multi-center, phase 2 clinical trial to evaluate the efficacy and safety of niraparib monotherapy for a recurrent or persistent rare fraction of gynecologic malignancies with mutations except for ovarian cancers. We will independently consider the effect of niraparib for uLMS or other gynecologic malignancies with mutations (cohort A, C) and HRD positive uLMS without mutations (cohort B). Participants must have 1–3 lines of previous chemotherapy and at least one measurable lesion according to RECIST (v.1.1). Niraparib will be orally administered once a day until lesion exacerbation or unacceptable adverse events occur. Efficacy will be evaluated by imaging through an additional computed tomography scan every 8 weeks. Safety will be measured weekly in cycle 1 and every 4 weeks after cycle 2 by blood tests and physical examinations. The sample size is 16–20 in each of cohort A and B, and 31 in cohort C. Primary endpoint is the objective response rate.

Time for enhancing government-led primary prevention of cervical cancer

민경진,서동훈,Tsukasa Baba,Xiaojun Chen,김재원,Yusuke Kobayashi,Janice Kwon,임명철,이정윤,Satoru Nagase,박정열,Siriwan Tangjitgamol,Hidemichi Watari 대한부인종양학회 2021 Journal of Gynecologic Oncology Vol.32 No.1

Phase 2 single-arm study on the safety of maintenance niraparib in Japanese patients with platinum-sensitive relapsed ovarian cancer

Kazuhiro Takehara,Takashi Matsumoto,Junzo Hamanishi,Kosei Hasegawa,Motoki Matsuura,Kiyonori Miura,Shoji Nagao,Hidekatsu Nakai,Naotake Tanaka,Hideki Tokunaga,Kimio Ushijima,Hidemichi Watari,Yoshihito Y 대한부인종양학회 2021 Journal of Gynecologic Oncology Vol.32 No.2

Objective: The primary objective of this study was to evaluate the safety of niraparib 300 mg/dayin Japanese patients with platinum-sensitive, relapsed ovarian cancer in a maintenance setting. Methods: Phase 2, multicenter, open-label, single-arm study enrolled Japanese patients withplatinum-sensitive, relapsed ovarian cancer who had received ≥2 platinum-based regimens. The primary endpoint (incidence of grade 3 or 4 thrombocytopenia-related events within 30days after initial niraparib administration) was justified by the incidences of a global pivotalphase 3 study and its post-hoc safety analysis on thrombocytopenia, the major hematologicaladverse event of niraparib. The overall safety analysis examined other treatment-emergentadverse events (TEAEs). Results: Enrolled patients (n=19) had a median (min, max) body weight of 53.9 (40.8–79.1)kg; all but one patient weighed <77 kg. Most (94.7%) patients initially received niraparib300 mg/day but this decreased in subsequent cycles (mean±standard deviation doseintensity, 191.6±65.7 mg/day). In total, 6/19 (31.6%) patients experienced grade 3 or 4 thrombocytopenia-related events within 30 days of initial niraparib administration. Other common TEAEs included nausea, and decreased platelet or neutrophil counts. Noprogression-free or overall survival events occurred; only 1 of 4 response-evaluable patientshad a post-baseline tumor assessment (stable disease). Conclusion: The incidence of grade 3 or 4 thrombocytopenia-related events in Japaneseovarian cancer patients was similar to that in the corresponding non-Japanese study. Overall,the safety profile was acceptable and consistent with the known safety profile and previousexperience with niraparib. Trial Registration: ClinicalTrials.gov Identifier: NCT03759587