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Profile of treatment-related complications in women with clinical stage IB-IIB cervical cancer: A nationwide cohort study in Japan.

ABSTRACT: OBJECTIVE:To examine clinico-pathological factors associated with surgical complications and postoperative therapy for clinical stage IB-IIB cervical cancer. METHODS:This nationwide multicenter retrospective study examined women with clinical stage IB-IIB cervical cancer who underwent radical hysterectomy plus pelvic and/or para-aortic lymphadenectomy between 2008-2009 at 87 institutions of the Japanese Gynecologic Oncology Group (n = 693). Multivariate models were used to identify independent predictors of perioperative grade 3-4 complications and bladder dysfunction. RESULTS:The overall intraoperative and postoperative complication rates were 3.3% and 9.8%, respectively. Clinical stage was not associated with perioperative complications (P = 0.15). Radiotherapy-based adjuvant therapy was significantly associated with an increased risk of postoperative complications (radiotherapy alone: adjusted-odds ratio [OR] 3.19, 95% confidence interval [CI] 1.46-6.99, P = 0.004; radiotherapy plus chemotherapy: adjusted-OR 3.26, 95%CI 1.66-6.41, P = 0.001), whereas chemotherapy was not (P = 0.45). Nerve-sparing surgery significantly reduced the risk of postoperative bladder dysfunction (adjusted-OR 0.57, 95%CI 0.37-0.90, P = 0.02) whereas adjuvant chemotherapy increased the risk of bladder dysfunction (adjusted-OR 2.06, 95%CI 1.16-3.67, P = 0.01). Among women receiving adjuvant chemotherapy, nerve-sparing radical hysterectomy significantly reduced the risk of bladder dysfunction (15.0% versus 32.9%, OR 0.31, 95%CI 0.14-0.68, P = 0.004). After propensity score matching, survival outcomes were similar with both types of adjuvant therapy (radiotherapy-based versus chemotherapy, P>0.05). CONCLUSION:Our study highlighted two distinct complication profiles of adjuvant therapy after radical hysterectomy for clinical stage IB-IIB cervical cancer, with radiotherapy increasing grade 3-4 adverse events and chemotherapy increasing bladder dysfunction. In this setting, nerve-sparing surgery may be useful if chemotherapy is being considered for adjuvant therapy.

SUBMITTER: Machida H

PROVIDER: S-EPMC6322763 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Profile of treatment-related complications in women with clinical stage IB-IIB cervical cancer: A nationwide cohort study in Japan.

Machida Hiroko H Matsuo Koji K Furusawa Akiko A Kita Tsunekazu T Kitagawa Ryo R Mikami Mikio M

PloS one 20190107 1

<h4>Objective</h4>To examine clinico-pathological factors associated with surgical complications and postoperative therapy for clinical stage IB-IIB cervical cancer.<h4>Methods</h4>This nationwide multicenter retrospective study examined women with clinical stage IB-IIB cervical cancer who underwent radical hysterectomy plus pelvic and/or para-aortic lymphadenectomy between 2008-2009 at 87 institutions of the Japanese Gynecologic Oncology Group (n = 693). Multivariate models were used to identif ...[more]

PMID: 30615679

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Project description:BackgroundEndometriosis, which occurs in approximately 10% of women of reproductive age, is defined as the presence of endometrial tissue outside the uterus. Women with endometriosis are more likely to have difficulty conceiving and tend to receive infertility treatment, including assisted reproductive technology (ART) therapy. There has not yet been a prospective cohort study examining the effects of endometriosis on pregnancy outcome in pregnant Japanese women.MethodologyThis was a prospective cohort study of the incidence of obstetrical complications in women with endometriosis using data of the Japan Environment & Children's Study (JECS). Included in this study were 9,186 pregnant women in the JECS with or without a history of endometriosis who gave birth or stillbirth or whose pregnancy was terminated with abortion between February and December 2011.Main outcome measuresThe effects of endometriosis on pregnancy outcome.ResultsOf the 9,186 pregnant women in the JECS, 4,119 (44.8%) had obstetrical complications; 330 participants reported a diagnosis of endometriosis before pregnancy, and these women were at higher risk for complications of pregnancy than those without a history of endometriosis (odds ratio (OR) = 1.50; 95% confidence interval (CI) 1.20 to 1.87). Logistic regression analyses showed that the adjusted OR for obstetrical complications of pregnant women who conceived naturally and had a history of endometriosis was 1.45 (CI 1.11 to 1.90). Among pregnant women with endometriosis, the ORs of preterm premature rupture of the membranes (PROM) and placenta previa were significantly higher compared with women never diagnosed with endometriosis who conceived naturally or conceived after infertility treatment, except for ART therapy (OR 2.14, CI 1.03-4.45 and OR 3.37, CI 1.32-8.65).ConclusionsThis study showed that endometriosis significantly increased the incidence of preterm PROM and placenta previa after adjusting for confounding of the data by ART therapy.

Project description:According to the National Comprehensive Cancer Network clinical practice guidelines of cervical cancer, concurrent chemoradiotherapy or radiotherapy is suggested for patients who receive radical hysterectomy and have intermediate- and high-risk cervical cancer. However, adjuvant chemotherapy has been increasingly chosen given the adverse events associated with chemoradiotherapy or radiotherapy and the increase in evidence regarding the efficacy of adjuvant chemotherapy. Given that adjuvant chemotherapy is not a standard treatment at present, if recurrence after adjuvant chemotherapy could be predicted, it would assist the decision of gynecological oncologists selecting which adjuvant therapy (chemotherapy or radiation therapy) to use. Cleft lip and palate transmembrane protein 1-like protein (CLPTM1L; also known as cisplatin resistance-related protein 9) is associated with apoptotic mechanisms and is related to the proliferation of the tumor cells and resistance against chemotherapy. In the present study, the association between CLPTM1L expression and recurrence of intermediate- and high-risk stage IB-IIB cervical cancer in patients undergoing radical hysterectomy followed by treatment with cisplatin and paclitaxel (TP) as adjuvant chemotherapy was determined. Patients were divided into two groups: Recurrence group and no-recurrence group. CLPTM1L expression was examined using immunohistochemistry in paraffin-embedded sections using weighted scores. Regarding the characteristics of the patients, a histology of non-squamous cell carcinoma, lymph node metastasis and parametrium invasion were more common in the recurrence group compared with the non-recurrence group. In the recurrence group, CLPTM1L expression was significantly higher than that in the no-recurrence group. Next, patients were divided into low and high-expression groups based on the weighted score with a cut-off value of 6. In the high expression group, patients exhibited a higher rate of recurrence (37.5 vs. 5.1%) and had worse overall survival. Multivariate analysis revealed that high CLPTM1L expression was independently related to recurrence. In in vitro analysis, small interfering RNA-mediated knockdown of CLPTM1L enhanced the sensitivity of cervical cancer cells to cisplatin. In conclusion, the present study revealed that CLPTM1L expression may be a predictive biomarker of recurrence of intermediate- and high-risk stage IB-IIB cervical cancer in patients undergoing radical hysterectomy followed by TP as adjuvant chemotherapy.

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Profile of treatment-related complications in women with clinical stage IB-IIB cervical cancer: A nationwide cohort study in Japan.

Publications

Profile of treatment-related complications in women with clinical stage IB-IIB cervical cancer: A nationwide cohort study in Japan.

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