Evaluation of the feasibility of human papillomavirus sponge-type self-sampling device at Japanese colposcopy clinics.

AIM: Self-sampling human papillomavirus (HPV) testing has been introduced for cervical cancer screening worldwide. In Japan, there are two types (brush and sponge) of HPV self-sampling devices. However, the recommended type for cervical cancer screening remains unclear. This study aimed to evaluate the feasibility of the HPV self-sampling device-sponge type (HSD-ST). Additionally, we aimed to examine the positive rate (sensitivity) for cervical intraepithelial neoplasia (CIN) 2 or worse using the HSD-ST. Finally, we aimed to perform a questionnaire survey regarding the usability of the HSD-ST. METHODS: We included 165 women who underwent HPV testing at one of three gynecologic clinics. First, the women used the HSD-ST and completed a questionnaire regarding its usability. Subsequently, they underwent physician-sampling HPV testing and cytology. We examined the agreement rate of HPV positivity between self- and physician-sampling HPV testing. RESULTS: The HPV-positive rates of self- and physician-collected samples were 59.4% and 62.4%, respectively, with an overall concordance rate of 88.5% and a calculated kappa coefficient of 0.76, indicating high concordance. Moreover, the positive (sensitivity) rates for CIN2 or worse were 81.4% and 89.8% in the self- and physician-collected samples, respectively. CONCLUSIONS: Our findings demonstrated the feasibility and usability of the HSD-ST.

Effectiveness of human papillomavirus vaccination in young Japanese women: a retrospective multi-municipality study.

In Japan, government support for human papillomavirus (HPV) vaccination began in November 2010. However, the mass media repeatedly reported on severe adverse events. The Japanese Ministry of Health, Labor and Welfare suspended proactive recommendations for HPV vaccines in June 2013. Japan's HPV vaccination rate dropped from 70% to less than 1% in 2017.We examined cervical cancer screening results in terms of abnormal cytology, histology, and HPV vaccination status among 11,903 women aged 20 to 25 y in the fiscal year 2015. The overall rate of HPV vaccination was 26.1% (3,112/11,903). Regarding cytology, the rate of atypical squamous cells of undetermined significance (ASC-US) or worse was 3.3% (103/3,112) in women who received HPV vaccination (vaccine (+) women) and 5.6% (496/8,791) in women who did not (vaccine (-) women). The rate of high-grade squamous intraepithelial lesion (HSIL) or worse was 0.26% (8/3,112) in vaccine (+) women and 0.81% (72/8,791) in vaccine (-) women. Regarding histology, the rate of cervical intraepithelial neoplasia 1 or worse (CIN1+) was 1.4% (42/3,112) in vaccine (+) women and 2.1% (178/8,791) in vaccine (-) women. The rates of CIN2+ and CIN3+ were similar regardless of vaccination. We found a significantly lower incidence of CIN in vaccine (+) women. These results suggest that the resumption of recommending HPV vaccination as primary prevention for cervical cancer is needed in Japan.

Long-term survival of patients with recurrent endometrial stromal sarcoma: a multicenter, observational study.

OBJECTIVE: The aim of this study was to evaluate the clinical behavior and management outcome of recurrent endometrial stromal sarcoma (ESS). METHODS: A retrospective review of charts of 10 patients with recurrent ESS was performed and relapse-free interval, relapse site, treatment, response to treatment, duration of follow-up and clinical outcome extracted. Survival outcome measures used were post-relapse survival which was defined as the time from first evidence of relapse to death from any cause. Living patients were censored at the date of last follow-up. RESULTS: The median age and median relapse-free interval at the time of initial relapse were 51.5 years and 66.5 months, respectively. The number of relapses ranged from one to five. Sixteen surgical procedures for recurrent disease included nine (56.0%) complete resections. There was no statistically significant difference between initial recurrent tumors and second/subsequent recurrent tumors in the rate of complete surgery (44.4% vs. 71.4%, respectively, p=0.36). Of the eleven evaluable occasions when hormonal therapy was used for recurrent disease, disease control was achieved in eight (72.7%). There was no difference between initial recurrent tumors and second/subsequent recurrent tumors in disease control rate by hormonal therapy (85.7% vs. 50.0%, respectively, p=0.49). The 10-year post-relapse survival rate was 90.0% and the overall median post-relapse survival 119 months (range, 7 to 216 months). CONCLUSION: Post-relapse survival of patients with ESS can be expected to be >10 years when treated by repeated surgical resection and hormonal therapy or both.

Prevalence, classification, and risk factors for postoperative lower extremity lymphedema in women with gynecologic malignancies: a retrospective study.

OBJECTIVE: Lower extremity lymphedema (LEL) is a major long-term complication of radical surgery. We aimed to estimate the incidence and grading of LEL in women who underwent lymphadenectomy and to evaluate risk factors associated with LEL. MATERIALS AND METHODS: We retrospectively reviewed 358 patients with cervical, endometrial, and ovarian cancer who underwent transabdominal complete systematic pelvic and para-aortic lymphadenectomy between 1997 and 2011. Lower extremity lymphedema was graded according to criteria of the International Society of Lymphology. Incidence of LEL and its correlation with various clinical characteristics were investigated using Kaplan-Meier survival and Cox proportional hazards methods. RESULTS: Overall incidence of LEL was 21.8% (stage 1, 60%; stage 2, 32%; and stage 3, 8%). Cumulative incidence increased with observation period: 12.9% at 1 year, 20.3% at 5 years, and 25.4% at 10 years. Age, cancer type, stage (International Federation of Gynecology and Obstetrics), body mass index, hysterectomy type, lymphocyst formation, lymph node metastasis, and chemotherapy were not associated with LEL. Multivariate analysis confirmed that removal of circumflex iliac lymph nodes (hazard ratio [HR], 4.28; 95% confidence interval [CI], 2.09-8.77; P < 0.0001), cellulitis (HR, 3.48; 95% CI, 2.03-5.98; P < 0.0001), and number of removed lymph nodes (HR, 0.99; 95% CI, 0.98-0.99; P = 0.038) were independent risk factors for LEL. CONCLUSIONS: Postoperative LEL incidence increased over time. The results of the present study showed a significant correlation with removal of circumflex iliac lymph nodes and cellulitis with the incidence of LEL. Multicenter or prospective studies are required to clarify treatment efficacies.

Tumor volume successively reflects the state of disease progression in endometrial cancer.

OBJECTIVE: This study aimed to clarify the clinical significance of tumor volume in endometrial cancer. METHODS: A total of 667 patients with endometrial cancer who underwent preoperative MRI and surgical treatment including lymphadenectomy were enrolled. As the surrogate marker of actual tumor volume, the volume index was defined as the product of the maximum longitudinal diameter along the uterine axis, the maximum intersecting anteroposterior diameter of the sagittal section image, and the maximum horizontal diameter of the horizontal section image from the MRI data. The volume index was divided into five categories: Group 1 (<8), Group 2 (8 to <27), Group 3 (27 to <64), Group 4 (64 to <125), and Group 5 (125 or more). The relationships between various clinicopathologic factors and volume index were investigated, and Cox regression analysis was conducted to assess the significance of volume index with respect to prognosis. RESULTS: High-risk clinicopathologic findings increased with tumor volume. The lymph node metastasis rate was 3% in Group 1, 9% in Group 2, 17% in Group 3, 25% in Group 4, and 53% in Group 5. Cox regression analysis showed that the volume index (≥36) was a prognostic factor (hazard ratio: 2.0, 95% confidence interval: 1.3-3.1) independent of older age (≥58 years), high-risk histological grade/subtype, deep myoinvasion, lymph node metastasis, and type of surgery. CONCLUSION: Tumor volume successively reflects the state of disease progression in endometrial cancer. The volume index can give information on both the staged prognosis and surgical management.

Factors influencing the number of pelvic and para-aortic lymph nodes removed in surgical treatment of endometrial and ovarian cancer.

OBJECTIVE: This study aimed to determine the number of lymph nodes (LNs) removed in patients who underwent abdominal complete systematic pelvic and para-aortic lymphadenectomy and to identify factors that contribute to disparity in the number of LNs removed. METHODS: We retrospectively reviewed 260 patients with endometrial cancer and ovarian cancer between 1997 and 2011. All pelvic and para-aortic LNs were submitted as 25 separate packets. The correlations of the number of LNs with age, year of surgery, the operating surgeon, pathologist, body mass index (BMI), histology, clinical stage, operating time, blood loss, and lymph node metastasis were investigated. RESULTS: The median number of LNs removed was 45 pelvic (17-92) and 25 para-aortic (6-69) LNs. Among pelvic LNs, the common iliac nodes were the most frequently removed followed by the obturator nodes. The median number of the left upper para-aortic LNs between the left renal vein and the inferior mesenteric artery was highest among para-aortic LNs. There were significant correlations between the total number of LNs removed and age (P = 0.036), histology (clear vs serous; P = 0.015), and BMI (P < 0.0001) in ovarian cancer. Features associated with higher LN count on multivariate linear regression analysis included younger patients (P = 0.038) and higher BMI (P = 0.012). CONCLUSIONS: Age and BMI are independently associated with higher LN counts during LN dissection in ovarian cancer. The present study results may be important when using LN counts as a surrogate for adequate lymphadenectomy.

A prospective study on the efficacy of octreotide in the management of malignant bowel obstruction in gynecologic cancer.

OBJECTIVE: Malignant bowel obstruction (MBO), of which symptoms lead to a poor quality of life, is a common and distressing clinical complication in advanced gynecologic cancer. The aim of this study was to prospectively assess the clinical efficacy of octreotide to control vomiting in patients with advanced gynecologic cancer with inoperable gastrointestinal obstruction. METHODS: Patients with advanced gynecologic cancer, who presented at least one episode of vomiting per day due to MBO, were enrolled in this prospective study from 2006 to 2009. Octreotide was administered when necessary at doses starting with 300 µg up to 600 µg a day by continuous infusion for 2 weeks. Primary end point was vomiting control, which was evaluated by common terminology criteria for adverse events version 3 (CTCAE v3.0). Adverse events were also evaluated by CTCAE v3.0. RESULTS: Twenty-two cases were enrolled in this study. Octreotide controlled vomiting in 15 cases (68.2%) to grade 0 and 3 cases (13.6%) to grade 1 on CTCAE v3.0. Overall response rate to octreotide treatment was 81.8% in our patients' cohort. Among 14 cases without nasogastric tube, the overall response rate was 93.1% (13/14). Among 8 cases with nasogastric tube, 4 cases were free of tube with decrease of drainage, and overall response rate was 62.5% (5/8). No major adverse events related to octreotide were reported. CONCLUSIONS: We conclude that 300-µg/d dose of octreotide was effective and safe for Japanese patients with MBO by advanced gynecologic cancer. Octreotide could contribute to better quality of life by avoiding placement of nasogastric tube.

Reduction/prevention of lower extremity lymphedema after pelvic and para-aortic lymphadenectomy for patients with gynecologic malignancies.

BACKGROUND: Lower extremity lymphedema (LEL) is a serious complication caused by lymphadenectomy in patients with gynecologic malignancies. In this study, we evaluated the effect of preserving the circumflex iliac lymph nodes (CILNs), i.e., the most caudal external iliac lymph nodes, for the prevention and reduction of LEL by comparing two groups of patients, one in which CILN were removed and the other in which CILNs were preserved. METHODS: We retrospectively reviewed 329 patients with gynecologic malignancies who had undergone abdominal complete systematic pelvic and para-aortic lymphadenectomy. The patients were divided into nonpreserved (n = 189) and preserved (n = 140) groups, depending on whether CILNs were removed. Primary outcome measures included the incidence and severity of LEL. RESULTS: The incidence of LEL was significantly lower in the preserved group than in the nonpreserved group (P < 0.0001). The frequency of LEL was also significantly lower in the preserved group than in the nonpreserved group regardless of the range of pelvic and para-aortic lymphadenectomy (P < 0.0001). LEL in the overwhelming majority of cases in the preserved group was mild, and no patients experienced severe LEL. Further, the incidence of cellulitis was 0% in the preserved group, while it was 12.7% in the nonpreserved group (P < 0.0001). Lymphoscintigraphy revealed collateral pathways from the preserved CILN along the iliac and large abdominal vessels. CONCLUSIONS: This method of lymph node preservation is a simple and extremely effective approach for preventing/reducing LEL after pelvic and para-aortic lymphadenectomy for patients with gynecologic malignancies.

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.

OBJECTIVE: 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.

Cytogenetic analysis of uterine leiomyoma: the size, histopathology and GnRHa-response in relation to chromosome karyotype.

OBJECTIVE: The aim of this study was to elucidate the clinical characteristics of uterine leiomyomas having abnormal chromosome karyotype. STUDY DESIGN: A total of 394 myomas were obtained from 213 patients for cytogenetic analysis. The size (number of nodules=144), histopathology (n=302), and gonadotropin-releasing hormone analogue (GnRHa)-response (n=58) were investigated in relation to chromosome karyotype in myomas. RESULTS: 302 myomas from 166 patients were successfully karyotyped. A total of 21 myomas from 21 patients showed abnormal chromosome karyotype. The high frequencies of involved chromosomes 12, 14, 1, 7 were observed. The diameters of myomas with abnormal karyotype were significantly larger than those of myomas with normal karyotype. The frequency of the degeneration in myomas with abnormal karyotype was significantly higher than that with normal karyotype. The reduction rate in size of myomas by GnRHa treatments did not differ between the two types (karyotype normal versus abnormal) of nodules. CONCLUSIONS: Chromosomally abnormal myomas were larger in diameter and showed a higher frequency of degeneration, suggesting that the cytogenetic background in uterine leiomyoma affects a tumor's growth potential.

A phase I/II study of carboplatin and paclitaxel in patients with epithelial ovarian cancer.

BACKGROUND: This study was conducted to investigate the recommended dose of paclitaxel for use in combination with a fixed dose of carboplatin and to evaluate the toxicity and efficacy of carboplatin-paclitaxel combination chemotherapy in patients with epithelial ovarian cancer. METHODS: One hundred and ten patients were enrolled in the Phase I/II study and 97 patients were evaluated for further analysis, excluding 13 ineligible patients or patients with infringement of protocol: 15 patients for the Phase I and 82 for the Phase II study. In the Phase I trial, we studied dose escalation using a carboplatin dose of AUC 5 and paclitaxel levels of 150, 175 and 200 mg/m(2). The grades of toxicity of the regimen of all patients enrolled in the Phase II study (n = 82), the progression-free survival time (PFS) of optimal-debulked patients and complete responders (n = 62) and the response rate of suboptimal-debulked patients (n = 39) were investigated. RESULTS: After observing grade 4 neutropenia in four of six patients in the paclitaxel 200 mg/m(2) administration group, we chose 175 mg/m(2) as the recommended dose of paclitaxel in this regimen. At this dose, the median of PFS and response rate were 432 days (range, 19-907 days) and 66.7%, respectively. CONCLUSION: Combination chemotherapy using paclitaxel 175 mg/m(2) and carboplatin AUC 5 is very well tolerated and highly effective for the treatment of ovarian cancer.

Para-aortic lymph node metastasis in relation to serum CA 125 levels and nuclear grade in endometrial carcinoma.

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.