Propensity score-matched analysis of systemic chemotherapy versus salvage hysterectomy for persistent cervical cancer after definitive radiotherapy/concurrent chemoradiotherapy.

BACKGROUND: The aim of the current study was to evaluate oncologic outcomes of patients who were treated with salvage hysterectomy (HT), compared to systemic chemotherapy (CT) for persistent cervical cancer after definitive radiotherapy (RT)/ concurrent chemoradiotherapy (CCRT). METHODS: Patients with persistent cervical cancer treated with definitive RT/CCRT at 35 institutions from 2005 to 2014 were reviewed retrospectively (n = 317). Those who underwent a HT for persistent cervical cancer after definitive RT/CCRT were matched with propensity scores for patients who underwent systemic CT. Oncologic outcomes between the two groups using a propensity score matched-cohort analysis were compared. RESULTS: A total of 142 patients with persistent cervical cancer after definitive RT/CCRT were included after matching (HT: 71, systemic CT: 71). All background factors between HT and CT groups were well balanced. Median overall survival was 3.8 and 1.5 years in the HT and CT groups, respectively (p = 0.00193, hazards ratio [HR] 0.41, 95% confidence interval [CI] 0.23-0.73), Increasing residual tumor size was significantly associated with a high incomplete resection rate (p = 0.016, Odds Ratio 1.11, 95%CI 1.02-1.22). Severe late adverse events occurred in 7 patients (9.9%) in the HT cohort. CONCLUSION: The current study demonstrated that, when compared to systemic CT, the adoption of salvage HT for patients with persistent cervical cancer after definitive RT/CCRT reduced mortality rate by about 60%. This indicates that salvage HT could be curative treatment for those patients. Further prospective clinical trials with regard to salvage HT after RT/CCRT are warranted.

A multi-institutional observational study on the effects of three-dimensional radiotherapy and weekly 40-mg/m2 cisplatin on postoperative uterine cervical cancer patients with high-risk prognostic factors.

BACKGROUND: The aim of this study was to evaluate the effects of treatment with both three-dimensional radiotherapy (3DRT) and weekly 40-mg/m2 cisplatin on postoperative uterine cervical cancer patients with high-risk prognostic factors. METHODS: We conducted a retrospective multi-institutional chart review of postoperative uterine cervical cancer patients with high-risk prognostic factors who had been treated with both 3DRT and weekly 40-mg/m2 cisplatin from 2007 to 2012. Each participating hospital provided detailed information regarding patient characteristics, treatment outcomes, and treatment complications. RESULTS: The eligible 96 patients were analyzed. The median follow-up period was 61 months. The 3-year relapse-free survival, overall survival (OS), and locoregional relapse-free survival (LRFS) rates were 76%, 90%, and 88%, respectively. In multivariate analysis, the histological finding of either adenocarcinoma or adenosquamous carcinoma was a significant risk factor for both OS and LRFS. The percentage of patients with grade ≥ 3 acute hematologic toxicity, acute lower gastrointestinal toxicity (GIT), and late lower GIT were 45%, 19%, and 17%, respectively. CONCLUSIONS: The outcomes of concurrent chemoradiotherapy (CCRT) using weekly 40-mg/m2 cisplatin are similar to those in the previous studies that used several chemotherapy regimens. However, postoperative CCRT using 3DRT had a high level of late GIT.

Relationship between metabolic syndrome and uterine leiomyomas: a case-control study.

BACKGROUND/AIMS: Uterine leiomyomas are the most common gynecological benign tumor and greatly affect reproductive health and well-being. The pathophysiology and epidemiology of fibroids are poorly understood. Obesity and elevated blood pressure have been reported to be predisposing factors. In this study, we investigated whether fibroids are associated with some criteria of the metabolic syndrome. METHODS: The case patients were 213 women who underwent hysterectomy or myomectomy for fibroids, and the control subjects were 159 women who underwent operation for benign indications other than fibroids. Preoperative information on body mass index (BMI), blood pressure (BP), serum triglyceride (TG) and fasting plasma glucose (FPG) was obtained from medical records. The patients were classified as overweight if they had a preoperatively measured BMI of > or =24.0, hypertensive if BP was > or =140/90 mm Hg, hypertriglyceridemic if TG was > or =150 mg/dl, and hyperglycemic if FPG was > or =110 mg/dl. RESULTS: BMI, BP, TG and FPG were significantly higher in the case group compared with the control group. In logistic regression analysis, fibroids were statistically significantly associated with being overweight and hypertensive. With the combination of these risk factors, the risk of fibroids increased. CONCLUSION: Uterine leiomyomas may share pathogenic features with the development of metabolic syndrome.

The concept of platinum sensitivity could be applied to recurrent cervical cancer: a multi-institutional retrospective study from the Japanese Gynecologic Oncology Group.

PURPOSE: This study aimed at evaluating the applicability of the concept of platinum sensitivity to recurrent cervical cancer. METHODS: The clinical information of patients with recurrent cervical cancer, who were initially treated with platinum-based chemotherapy and received second-line platinum-based chemotherapy at the time of recurrence between January 2008 and December 2012, was retrospectively reviewed. RESULTS: A total of 677 patients from 71 medical centers were analyzed. The median overall survival (OS) for patients with platinum-free interval (PFI) of <6, 6-11, 12-17, and ≥18 months was 12.1 (95% CI 11.0-14.1) months, 17.4 (15.5-20.4) months, 20.2 (17.9-27.6) months, and 29.9 (26.7-36.0) months, respectively (P < 0.0001, log-rank). The best cut-off value of PFI that affected OS was 7 months, analyzed by the minimum P value method. The median progression-free survival (PFS) for patients with less than and more than PFI of 7 months was 6.2 months (95% CI 4.8-9.3) and 21.0 months (18.9-24.8) (P < 0.0001, log-rank), respectively, and the median OS for patients with less than and more than PFI of 7 months was 12.3 months (11.2-14.1) and 24.2 months (20.8-25.8) (P < 0.0001, log-rank). Multivariate analysis revealed that PFI (P < 0.0001, HR 0.449, 95% CI 0.369-0.548) alone had a statistically significant association with OS. CONCLUSIONS: This study showed that the concept of platinum sensitivity could be applied to recurrent cervical cancer and PFI could be one of the independent prognostic factors for patients with recurrent cervical cancer who have previously been treated with platinum-based chemotherapy.

Fractalkine (FRK) levels in amniotic fluid and its production during pregnancy.

Fractalkine is a new CX(3)C chemokine that has chemoattractant activity for T cells, monocytes and natural killer (NK) cells. Western blot analysis revealed that fractalkine protein was detected as a 95 kDa band in both the amniotic fluid and the amnion during the second and third trimesters. Immunohistochemistry using an anti-fractalkine polyclonal antibody revealed positive staining of epithelial cells in amnion and trophoblasts in both the second and third trimesters. Neonatal urine also contained detectable amounts of fractalkine. RT-PCR detected fractalkine mRNA transcripts in the amnion. To determine whether fractalkine receptor (CX(3)CR1)-positive cells were present in amniotic fluid and amnion, we performed RT-PCR using specific primers for CX(3)CR1. CX(3)CR1-positive cells had migrated into the amniotic fluid and the amnion. The present findings suggest that fractalkine found in amniotic fluid may contribute to the immunodefence mechanism during pregnancy.

The expression of secretory leukocyte protease inhibitor (SLPI) in the fallopian tube: SLPI protects the acrosome reaction of sperm from inhibitory effects of elastase.

BACKGROUND: Secretory leukocyte protease inhibitor (SLPI) is a protein found in various fluids, including parotid secretions, cervical mucus, seminal plasma and ascites, and is a potent inhibitor of human leukocyte elastase activity. The objective of the study was 2-fold, to evaluate (i) the presence of SLPI in the Fallopian tube, and (ii) the effect of SLPI on the acrosome reaction of sperm. METHODS AND RESULTS: Western blot analysis revealed that SLPI protein was detected as a 12 kDa band in the isthmus, ampulla and infundibulum of the Fallopian tube. Immunohistochemistry using an anti-SLPI polyclonal antibody revealed positive staining of epithelial cells in the Fallopian tube. RT-PCR demonstrated that SLPI transcripts were expressed in the Fallopian tube. To determine the function of SLPI in the Fallopian tube, the effects of SLPI and elastase on the sperm acrosome reaction were examined. SLPI prevented the reduction of the acrosome reaction by elastase in a dose-dependent manner. CONCLUSION: The present findings suggest that SLPI in the Fallopian tube contributes to sperm-oocyte interaction.