Effectiveness of catch-up and routine program of the 9-valent vaccine on cervical cancer risk reduction in Japan.

In 2013, the national human papillomavirus (HPV) immunization program began. However, in June 2013, Japan's Ministry of Health, Labor and Welfare (MHLW) announced a "temporary" suspension of its recommendation for the human papillomavirus vaccine. Finally, in November 2021, the MHLW ended its suspension of the recommendation of the HPV vaccine. To address the 9-year gap in HPV vaccinations the suspension had caused, the MHLW conducted a program of catch-up vaccinations from April 2022 to March 2025. Finally, in April 2023, the 9-valent HPV vaccine was approved for both the routine and catch-up vaccination programs in Japan. In this study, we investigated the potential effects of the introduction of the 9-valent vaccine on the increased risk of cervical cancer in females born after fiscal year (FY) 2000. We estimated the lifetime relative risk of cervical cancer incidence and death using the improved routine and catch-up vaccination rates after the recent resumption of the governmental recommendation for women and girls to have the HPV vaccination. These relative risks were calculated using a lifetime risk of 1.000 for cervical cancer incidence and death for females born in FY 1993. We predicted that even if a 90% vaccination rate were to be achieved by FY 2024 with the 9-valent vaccine among women born between FY 2000 and FY 2005, the risk would remain higher than for the vaccination generation. Therefore, for women born between FY 2000 and FY 2005, it will be necessary to significantly improve the cervical cancer screening rate to compensate for this increased risk.

Disparities among Japanese municipalities in recommendations for routine and catch-up HPV vaccinations.

In November 2021, the government of Japan announced a reversal of its decision in 2013 to suspend the previous proactive recommendation for HPV vaccination. However, the program for young girls to receive routine and catch-up vaccinations has not necessarily developed as expected. We conducted a nationwide questionnaire survey by mail in September 2022. The survey was mailed to 133 municipalities consisting of all cities/wards of the Tokyo and Osaka Prefectures and all other prefectural capital cities. Responses were received from 82 municipalities (62.7%). Notification of routine HPV vaccinations had already been sent to 76 (92.7%) of the municipalities; 70 (85.4%) had been encouraged to promote catch-up vaccinations. The questionnaire forms for registration and pre-vaccination screening for routine immunization had been sent to 74.1% (60/81) of the municipalities and 68.8% (55/80) for catch-up immunizations. For catch-up vaccination, only 54 municipalities (65.9%) had detailed vaccination records for those eligible. In total, 10 municipalities (12.2%) had virtually no vaccination records because these had already been discarded. In addition, 61 municipalities (74.4%) had notified only women and girls eligible for a catch-up vaccination based on their vaccination record, whereas 25.6% (21/82) of the municipalities reported that they had sent, or would send, the notification to all women and girls within the targeted grades, including those who had already been vaccinated with three injections. The survey revealed disparities among the municipalities in their HPV vaccine notification processes. Future research on monitoring HPV vaccination rates and incidence rates of cervical cancer and precancerous lesions in each municipality will be desirable.

Intentions for catch-up HPV vaccination in Japan: an internet survey.

PURPOSE: In Japan, Japan's Ministry of Health, Labor, and Welfare decided to suspend govermental recommendation for HPV vaccination in FY 2013. The HPV vaccination rate for those born in FY 2000 or thereafter declined dramatically. In 2021, the "suspension of recommendation" ended. The catch-up vaccinations for the unvaccinated have been offered nationwide from FY 2022 to FY 2024. We aimed to quantify the vaccination intentions and characteristics of those young women now eligible for catch-up vaccination.  METHODS: In February of 2022, we conducted an internet survey targeted women who were born in 1997-2004 but who had not yet been HPV vaccinated. RESULTS: We received 1,648 valid responses. 41.6% of the respondents wanted to uptake the catch-up HPV vaccination, 29.7% were undecided, and 28.7% did not want to be vaccinated. The intention to uptake catch-up HPV vaccination was associated with a good history of gynecological visits, intention to receive cervical cancer screening, sexual activity, degree of anxiety about cervical cancer, familiarity with problems associated with cervical cancer, experience with vaccination recommendations, and knowledge about cervical cancer (p < 0.05, respectively). In the vaccinated generation, the proportion of the group that did not want to be vaccinated was significantly higher (p < 0.05). In the vaccine-suspended generation, the proportion of the group that wanted to be vaccinated was significantly higher (p < 0.05). CONCLUSION: Our survey revealed that catch-up vaccination intentions differed depending on the vaccination environment. It is necessary for all organizations involved with HPV vaccination, such as government, medical institutions, and educational institutions, to make recommendations based on an understanding of the characteristics of the "vaccinated generation" and the "vaccine-suspended generation".

A single institution's experience with minimally invasive surgery for ovarian cancer, and a systematic meta-analysis of the literature.

BACKGROUND: This study assesses the feasibility of minimally invasive surgery (MIS) for well-selected epithelial ovarian cancer (EOC) patients. METHODS: We performed a review of data prospectively collected from a single center from 2017 to 2022. Only patients with histologically confirmed EOC, with a tumor diameter of less than 10 cm, were eligible. We also performed a meta-analysis of similar studies comparing the outcomes of laparoscopy and laparotomy. We used MINORS (Methodological Index for Non-Randomized Studies) to assess the risk of bias and calculated the odds ratio or mean difference. RESULTS: Eighteen patients were included; 13 in re-staging group, four in PDS group, and one in IDS group. All achieved complete cytoreduction. One case was converted to laparotomy. The median number of removed pelvic lymph nodes was 25 (range 16-34), and 32 (range 19-44) for para-aortic nodes. There were two (15.4%) intraoperative urinary tract injuries. The median follow-up was 35 months (range 1-53). Recurrence was observed in one case (7.7%). Thirteen articles for early-stage ovarian cancer were included in our meta-analysis. Analysis of the pooled results found that MIS had a higher frequency of spillage (OR, 2.15; 95% CI 1.27-3.64). No differences were observed in recurrence, complications, or up-staging. CONCLUSIONS: Our experience supports the possibility of conducting MIS for EOC in well-selected patients. Except for spillage, our meta-analysis findings are consistent with previous reports, the majority of which were also retrospective. Ultimately, randomized clinical trials will be needed to authenticate the safety.

Overview of laparoscopic surgery for cervical cancer in Japan: Updates after the laparoscopic approach to cervical cancer trial.

Laparoscopic radical hysterectomy (LRH) for cervical cancer has been reported to be similar oncologic outcome compared to abdominal radical hysterectomy (ARH) in many retrospective studies. In Japan, LRH has been covered by insurance since April 2018. In 2018, the same year that LRH became covered by insurance, Ramirez et al. at MD Anderson Cancer Center reported the results of a large phase III laparoscopic approach to cervical cancer trial (LACC trial) on the prognosis of open versus laparoscopic/robot-assisted minimally invasive radical hysterectomy. The results showed that minimally invasive approaches were associated with a higher rate of recurrence and death. At this point, it is not clear what is wrong with LRH and why it has a poorer prognosis compared to ARH. In this report, after the LACC report, we would like to review the current status of minimally invasive surgery for cervical cancer and future directions.

Anti-lipolysis-stimulated lipoprotein receptor monoclonal antibody as a novel therapeutic agent for endometrial cancer.

BACKGROUND: Endometrial cancer (EC) is a common gynecologic malignancy and patients with advanced and recurrent EC have a poor prognosis. Although chemotherapy is administered for those patients, the efficacy of current chemotherapy is limited. Therefore, it is necessary to develop novel therapeutic agents for EC. In this study, we focused on lipolysis-stimulated lipoprotein receptor (LSR), a membrane protein highly expressed in EC cells, and developed a chimeric chicken-mouse anti-LSR monoclonal antibody (mAb). This study investigated the antitumor effect of an anti-LSR mAb and the function of LSR in EC. METHODS: We examined the expression of LSR in 228 patients with EC using immunohistochemistry and divided them into two groups: high-LSR (n = 153) and low-LSR groups (n = 75). We developed a novel anti-LSR mAb and assessed its antitumor activity in an EC cell xenograft mouse model. Pathway enrichment analysis was performed using protein expression data of EC samples. LSR-knockdown EC cell lines (HEC1 and HEC116) were generated by transfected with small interfering RNA and used for assays in vitro. RESULTS: High expression of LSR was associated with poor overall survival (hazard ratio: 3.53, 95% confidence interval: 1.35-9.24, p = 0.01), advanced stage disease (p = 0.045), deep myometrial invasion (p = 0.045), and distant metastasis (p < 0.01). In EC with deep myometrial invasion, matrix metalloproteinase (MMP) 2 was highly expressed along with LSR. Anti-LSR mAb significantly inhibited the tumor growth in EC cell xenograft mouse model (tumor volume, 407.1 mm3 versus 726.3 mm3, p = 0.019). Pathway enrichment analysis identified the mitogen-activated protein kinase (MAPK) pathway as a signaling pathway associated with LSR expression. Anti-LSR mAb suppressed the activity of MAPK in vivo. In vitro assays using EC cell lines demonstrated that LSR regulated cell proliferation, invasion, and migration through MAPK signaling, particularly MEK/ERK signaling and membrane-type 1 MMP (MT1-MMP) and MMP2. Moreover, ERK1/2-knockdown suppressed cell proliferation, invasion, migration, and the expression of MT1-MMP and MMP2. CONCLUSIONS: Our results suggest that LSR contributes to tumor growth, invasion, metastasis, and poor prognosis of EC through MAPK signaling. Anti-LSR mAb is a potential therapeutic agent for EC.

Postoperative lymphocyst formation after pelvic lymphadenectomy for gynecologic cancers: comparison between laparoscopy and laparotomy.

PURPOSE: The goal of this study was to evaluate, using definitive diagnostic criteria, the incidence of lymphocyst formation following pelvic lymphadenectomy for gynecological cancer, and to compare rates between the approaches of laparoscopy and laparotomy. METHODS: We retrospectively reviewed the medical records of all patients who underwent pelvic lymphadenectomy for cervical or endometrial cancer between March of 2010 and March of 2016. We defined a lymphocyst as a circumscribed collection of fluid within the pelvic cavity, with a diameter of 2 cm or more, as diagnosed with ultrasound or computed tomography. RESULTS: During the six-year observational period, a pelvic lymphadenectomy was conducted in 196 women with clinical stage I uterine cancer; 90 cases underwent laparoscopy, 106 underwent laparotomy. The minimally invasive laparoscopic group had a lower estimated blood loss (p < 0.01), shorter hospital stay (p < 0.01). Lymphocysts were observed in 14.4% (13/90) of the laparoscopy cases, and in 15.1% (16/106) of the laparotomy cases which means no significant difference of lymphocyst (p = 1.00). The median size of symptomatic lymphocyst was significantly larger in laparotomy group than in laparoscopy group (4.8 cm v.s. 2.8 cm, median) (p = 0.04). Symptomatic lymphocysts were more common in laparotomy [7/90 (7.8%) vs 14/106 (13.2%) (p = 0.253)]. CONCLUSIONS: In a retrospective analysis with a strict diagnostic criteria, we could find no statistical difference in lymphocyst occurrence between laparoscopy and laparotomy. The median size of the lymphocyst was bigger and lymphocyst was likely to be symptomatic in the laparotomy group.

Attitudes and behaviors of obstetricians and gynecologists toward HPV vaccination: a 7-year follow-up survey in Japan.

BACKGROUND: In Japan, the government suspended HPV vaccine recommendation in 2013, resulting in dropping vaccination uptake to almost zero. We conducted four serial surveys on our colleague' attitude to HPV vaccination between 2014 and 2021. Here, we evaluate the result of the survey in 2021 and compare it to previous surveys. METHODS: The subjects were 567 obstetricians and gynecologists who had been trained in our university hospital or our affiliated hospitals. We used a questionnaire similar in format to those used in 2014, 2017, and 2019. RESULTS: A total of 340 doctors (60.0%) completed the survey. Among them, 93.2% (317/340) of respondents thought that the government should restart HPV vaccination recommendation, and that 63.2% (215/340) think male teenagers should also vaccinate against HPV. The percentage of teenaged daughters inoculated with HPV vaccination after Japanese government had suspended its recommendation was 43.5% (20/46), an increasing trend from the previous surveys. 39 out of the 46 daughters (84.8%) would be expected to receive full HPV vaccination after they take junior high school entrance examination or after 9-valent HPV vaccination is designated as a national routine-immunization. CONCLUSION: This study revealed increasing number of our colleagues think HPV vaccination is necessary for prevention of cervical cancer. The Japanese government's decision to resume its recommendation of the HPV vaccine in November 2021 will lead to a change in the public's thinking and behavior toward the HPV vaccine.

Change of HPV vaccination rates in Japan: the effect of individual notifications implemented by local governments.

BACKGROUND: In Japan, in June 2013, The Ministry of Health, Labor and Welfare (MHLW) decided to temporarily suspend its official recommendation for the participation of girls in the national immunization program. The HPV vaccination rate in Japan soon declined to below 1%. In October 2020, the MHLW notified that the municipalities could and should begin to individually notify girls and their parents targeted for routine vaccination. We have examined how that type of individual notification has affected the number of vaccinations. METHODS: From 12 municipalities (with a combined total population of approximately 4.06 million), we collected vaccination data for all girls who attended grades 6 through 10 from April 2019 to March 2021. We analyzed the number of initial-round vaccinations that occurred by month and the timing and the subjects of the individual notifications. RESULTS: The annual vaccination rate for tenth-grade students in 2020 in the six municipalities that had implemented individual notification was 9.46% (342/3618), which was significantly higher than the rate of 3.22% (54/1676) in the three municipalities that had not implemented individual notification (p < 0.001). On the other hand, the annual vaccination rate for the sixth to ninth-grade students in 2020 in the six municipalities that had implemented individual notification was not significantly (p = 0.56) higher than the rate in the three municipalities that did not: 1.43% (197/13,785) versus 1.33% (83/6260), respectively. CONCLUSION: This study clearly demonstrates the importance of providing information for routine vaccination directly to the targets and their parents.

The 'best friend effect': a promising tool to encourage HPV vaccination in Japan.

BACKGROUND: In Japan, HPV vaccination rates has dramaticaly declined since 2013. Since mothers are the ones making the decision to vaccinate their daughters against HPV, we probed the mothers' intention to receive vaccinations for themselves and to vaccinate their daughters against HPV, and their reasoning. METHODS: An internet survey was conducted in March of 2021. Through the screening, 1576 participants were extracted from a survey panel and divided into 3 groups based on their daughter's birth fiscal year (Group 1: 1994 to 1999, Group 2: 2000 to 2003, Group3: 2004 to 2008). The chi-square test and residual analysis were used for the statistical analysis of comparison among the groups. Logistic regression analysis was used to identify independent variables with mothers intention to get their daughters vaccinated under specific situations. RESULTS: The percentage of respondents without anxiety regarding their daughter's general vaccination was significantly higher in Group 1 (p < 0.05). In the mothers of daughters born in or after 2000 when vaccination rates declined (Groups 2 and 3), a situation in which 'The daughter's best friends were vaccinated before her' made the mothers think positively about HPV vaccination, and to the same degree as a situation in which 'You received a notice from your local government recommending vaccination' (Group 2: 41.6% (214/514) and 40.5% (208/514), Group 3: 48.5% (257/530) and 47.0% (249/530)). CONCLUSION: If mothers who have had their daughters vaccinated were to recommend HPV vaccination to their close friends, 'the best friend effect' should promote others to be vaccinated.

Copper ions are novel therapeutic agents for uterine leiomyosarcoma.

BACKGROUND: Multidrug resistance is a major concern in uterine leiomyosarcoma treatment. Development of effective chemotherapies and management of drug resistance in patients is necessary. The copper efflux transporter adenosine triphosphatase copper transporting beta is a member of the P-type adenosine triphosphatase family and is also known as a strong platinum efflux transporter. Various reports have shown the association between adenosine triphosphatase copper transporting beta and platinum resistance; however, suitable inhibitors or methods for inhibiting platinum efflux via adenosine triphosphatase copper transporting beta are not developed. OBJECTIVE: Our study focused on platinum resistance in uterine leiomyosarcoma. The role of adenosine triphosphatase copper transporting beta in uterine leiomyosarcoma resistance to platinum drugs was investigated both in vitro and in vivo. STUDY DESIGN: Adenosine triphosphatase copper transporting beta expression was investigated by Western blotting and the efficacy of copper sulfate pretreatment and cisplatin administration in adenosine triphosphatase copper transporting beta-expressing cells was investigated both in vitro and in vivo. RESULTS: Western blot analysis of SK-LMS-1 cells (uterine leiomyosarcoma cell line) revealed strong adenosine triphosphatase copper transporting beta expression. A permanent SK-LMS-ATPase copper transporting beta-suppressed cell line (SK-LMS-7B cells) was generated, and cisplatin exhibited a significant antitumor effect in SK-LMS-7B cells, both in vitro (SK-LMS-1 cells, half-maximal inhibitory concentration, 17.2 µM; SK-LMS-7B cells, half-maximal inhibitory concentration, 4.2 µM, P < .01) and in xenografts compared with that in SK-LMS-1 cells (5.8% vs 62.8%, P < .01). Copper sulfate was identified as a preferential inhibitor of platinum efflux via adenosine triphosphatase copper transporting beta. In SK-LMS-1 cells pretreated with 15 µM copper sulfate for 3 hours, the cisplatin half-maximal inhibitory concentration decreased significantly compared with that in untreated cells and resulted in significantly increased intracellular platinum accumulation (1.9 pg/cell vs 8.6 pg/cell, P < .01). The combination of copper sulfate pretreatment with cisplatin administration was also effective in vivo and caused cisplatin to exhibit significantly increased antitumor effects in mice with SK-LMS-1 xenografts (3.1% vs 62.7%, P < .01). CONCLUSION: Our study demonstrates that adenosine triphosphatase copper transporting beta is overexpressed in uterine leiomyosarcoma cells and that copper sulfate, which acts as an inhibitor of platinum efflux via adenosine triphosphatase copper transporting beta, may be a therapeutic agent in the treatment of uterine leiomyosarcoma.

Association of statins, aspirin, and venous thromboembolism in women with endometrial cancer.

OBJECTIVE: The anti-thrombogenic effects of statins and aspirin have been reported in various malignancies but have not been well examined in endometrial cancer. This study examined the association between statin and/or aspirin use and venous thromboembolism (VTE) risk in endometrial cancer. METHODS: This is a multi-center retrospective study examining 2527 women with endometrial cancer between 2000 and 2015. Statin and aspirin use at diagnosis was correlated to VTE risk during follow-up on multivariable analysis. RESULTS: There were 132 VTE events with a 5-year cumulative incidence rate of 6.1%. There were 392 (15.5%) statin users and 219 (8.7%) aspirin users, respectively. On multivariable analysis, statin use was associated with an approximately 60% decreased risk of VTE when compared to non-users (5-year cumulative rates 2.5% versus 6.7%, adjusted-hazard ratio [HR] 0.42, 95% confidence interval [CI] 0.19-0.92, P = 0.030) whereas aspirin did not demonstrate statistical significance (2.0% versus 6.5%, adjusted-HR 0.54, 95%CI 0.19-1.51, P = 0.24). There was a trend of joint effect between statin and aspirin although it did not demonstrate statistical significance: VTE risks for dual statin/aspirin user (adjusted-HR 0.27, 95%CI 0.04-2.07), statin alone (adjusted-HR 0.40, 95%CI 0.18-0.93), and aspirin alone (adjusted-HR 0.51, 95%CI 0.16-1.64) compared to non-use after adjusting for patient characteristics, tumor factors, treatment types, and survival events (P-interaction = 0.090). When stratified by statin type, simvastatin demonstrated the largest reduction of VTE risk (5-year cumulative rates 1.1% versus 6.7%, adjusted-HR 0.17, 95%CI 0.02-1.30, P = 0.088). Obesity, absence of diabetes mellitus, type II histology, and recurrent disease were the factors associated with decreased VTE risk with statin use (all, P-interaction<0.05). CONCLUSION: Our study suggests that statin use may be associated with decreased risk of VTE in women with endometrial cancer.

Recurrence, death, and secondary malignancy after ovarian conservation for young women with early-stage low-grade endometrial cancer.

OBJECTIVE: To examine the association between ovarian conservation and oncologic outcome in surgically-treated young women with early-stage, low-grade endometrial cancer. METHODS: This multicenter retrospective study examined women aged <50 with stage I grade 1-2 endometrioid endometrial cancer who underwent primary surgery with hysterectomy from 2000 to 2014 (US cohort n = 1196, and Japan cohort n = 495). Recurrence patterns, survival, and the presence of a metachronous secondary malignancy were assessed based on ovarian conservation versus oophorectomy. RESULTS: During the study period, the ovarian conservation rate significantly increased in the US cohort from 5.4% to 16.4% (P = 0.020) whereas the rate was unchanged in the Japan cohort (6.3-8.7%, P = 0.787). In the US cohort, ovarian conservation was not associated with disease-free survival (hazard ratio [HR] 0.829, 95% confidence interval [CI] 0.188-3.663, P = 0.805), overall survival (HR not estimated, P = 0.981), or metachronous secondary malignancy (HR 1.787, 95% CI 0.603-5.295, P = 0.295). In the Japan cohort, ovarian conservation was associated with decreased disease-free survival (HR 5.214, 95% CI 1.557-17.464, P = 0.007) and an increased risk of a metachronous secondary malignancy, particularly ovarian cancer (HR 7.119, 95% CI 1.349-37.554, P = 0.021), but was not associated with overall survival (HR not estimated, P = 0.987). Ovarian recurrence or metachronous secondary ovarian cancer occurred after a median time of 5.9 years, and all cases were salvaged. CONCLUSION: Our study suggests that adoption of ovarian conservation in young women with early-stage low-grade endometrial cancer varies by population. Ovarian conservation for young women with early-stage, low-grade endometrial cancer may be potentially associated with increased risks of ovarian recurrence or metachronous secondary ovarian cancer in certain populations; nevertheless, ovarian conservation did not negatively impact overall survival.

Histologic correlation between smartphone and coloposcopic findings in patients with abnormal cervical cytology: experiences in a tertiary referral hospital.

BACKGROUND: Smartphones recently have been applied in the medical setting. However, the literature evaluating the utility of smartphones in gynecologic oncology is limited. OBJECTIVE: To evaluate the utility of a smartphone in the detection of uterine cervical lesions in patients with abnormal cervical cytology. STUDY DESIGN: Seventy-five women with abnormal cervical cytology were enrolled. Two doctors independently inspected the uterine cervix by using smartphone or colposcopy. Images were captured using acetic acid, and biopsies were taken as standard-of-care procedures. The diagnostic performance of the smartphone for cervical intraepithelial neoplasm 1 or worse and cervical intraepithelial neoplasm 2 or worse were evaluated, and the kappa value was calculated to determine the chance corrected agreement of the histologic diagnoses based on the smartphone and colposcopic findings. RESULTS: There was a substantial agreement between histologic diagnoses based on the smartphone and colposcopic findings, with a kappa value of 0.67 (95% confidence interval, 0.43-0.90). The sensitivity, specificity, positive predictive value, and negative predictive value of the smartphone in the diagnosis of cervical intraepithelial neoplasm 1 or worse were 0.89 (95% confidence interval, 0.79-0.96), 0.33 (95% confidence interval, 0.08-0.70), 0.91 (95% confidence interval, 0.81-0.97), and 0.30 (95% confidence interval, 0.07-0.65), respectively. The sensitivity, specificity, positive predictive value, and negative predictive value in the diagnosis of cervical intraepithelial neoplasm 2 or worse were 0.92 (95% confidence interval, 0.81-0.98), 0.24 (95% confidence interval, 0.09-0.45), 0.71 (95% confidence interval, 0.58-0.81), and 0.60 (95% confidence interval, 0.26-0.88), respectively. CONCLUSION: We found that there was a substantial agreement between the histologic diagnoses based on the smartphone and colposcopic findings. The smartphone seems to be useful and may be an alternative to colposcopy.

Trends in incidence and long-term survival of Japanese women with vulvar cancer: a population-based analysis.

OBJECTIVE: The incidence and long-term survival analysis for vulvar cancer, due to its rarity, has not been fully described in Asian population. The objective of the study is to determine the trends in incidence and long-term survival for vulvar cancer in a Japanese population, using a population-based cancer registry data in Osaka, Japan. METHODS: The age-standardized incidence rate of 389 cases of vulvar squamous cell carcinoma (SCC) diagnosed between 1976 and 2010 was calculated, using the 1985 model population of Japan. The annual percentage change (APC) of the age-standardized incidence was estimated by the joinpoint regression models. The 5- and 10-year relative survival of 290 cases with vulvar SCC diagnosed between 1976 and 2008 were analyzed, using a cohort or period approach. Using the 10-year relative survival, the conditional 5-year survival for patients who lived for some years after diagnosis was also calculated. RESULTS: We have found that the age-standardized incidence rate for vulvar cancer trended downward during the period of 1979-1992 (APC - 6.3%; 95% confidence interval (CI) [- 11.3% to - 1.0%]), whereas it trended upward from 1993 to 2010 (APC 1.9%; 95% CI [- 0.7% to 4.6%]). There was no statistically significant difference for the 5- and 10-year relative survival between the two periods of 1976-2000 and 2001-2008. A statistically significant increase in the conditional 5-year survival at 2 years after diagnosis was observed (48.4%; 95% CI [41.1-55.3] versus 75.6%; 95% CI [64.0-83.9]). CONCLUSION: Despite an increasing trend in vulvar cancer incidence among Japanese population, the relative survival rate for vulvar cancer did not change over the 35 years of this study. We found that the conditional 5-year survival for vulvar cancer, as patients survived additional years, approached within reach of 100%. These data can provide valuable information for both patients and clinicians.

Retrospective analysis for predictors of parametrial involvement in IB cervical cancer.

AIM: The use of less radical surgery for early stage cervical cancer has often been discussed. To better determine eligible candidates for less radical surgery, we investigated the risk factors for parametrial involvement (PI). METHODS: The study included 193 patients with International Federation of Gynecology and Obstetrics (FIGO) stage IB cervical cancer who were treated with radical hysterectomy and pelvic lymphadenectomy between 2008 and 2014. The patients were divided into two groups according to whether or not the parametrium was involved pathologically. The two groups were compared with regards to clinical and histopathological variables. RESULTS: Univariate analysis showed that International Federation of Gynecology and Obstetrics stage, clinical tumor size, depth of stromal invasion, lymphovascular space invasion and pelvic lymph node metastasis were significantly associated with PI (P < 0.05 each). Multivariate analysis showed pelvic lymph node metastasis was an independent risk factor for PI (odds ratio, 10.70; [95% confidence interval, 3.02-48.08]; P = 0.0006). All patients with clinical tumor size less than or equal to 2 cm and negative for pelvic lymph node metastasis had no PI. CONCLUSION: Cervical cancer with the tumor less than or equal to 2 cm and negative for pelvic lymph node metastasis seldom has PI. These patients are good candidates for less radical surgery.

Significance of abnormal peritoneal cytology on survival of women with stage I-II endometrioid endometrial cancer.

OBJECTIVE: To examine survival of women with stage I-II endometrioid endometrial cancer whose peritoneal cytology showed malignant or atypical cells (abnormal peritoneal cytology). METHODS: This is a multi-center retrospective study examining 1668 women with stage I-II endometrioid endometrial cancer who underwent primary hysterectomy with available peritoneal cytology results between 2000 and 2015. Abnormal peritoneal cytology was correlated to clinico-pathological characteristics and oncological outcome. RESULTS: Malignant and atypical cells were seen in 125 (7.5%) and 58 (3.5%) cases, respectively. On multivariate analysis, non-obesity, non-diabetes mellitus, cigarette use, and lympho-vascular space invasion were independently associated with abnormal peritoneal cytology (all, P<0.05). Abnormal peritoneal cytology was independently associated with decreased disease-free survival (hazard ratio 3.07, P<0.001) and cause-specific survival (hazard ratio 3.42, P=0.008) on multivariate analysis. Abnormal peritoneal cytology was significantly associated with increased risks of distant-recurrence (5-year rates: 8.8% versus 3.6%, P=0.001) but not local-recurrence (5.2% versus 3.0%, P=0.32) compared to negative cytology. Among women with stage I disease, abnormal peritoneal cytology was significantly associated with an increased risk of distant-recurrence in the low risk group (5-year rates: 5.5% versus 1.0%, P<0.001) but not in the high-intermediate risk group (13.3% versus 10.8% P=0.60). Among 183 women who had abnormal peritoneal cytology, postoperative chemotherapy significantly reduced the rate of peritoneal recurrence (5-year rates: 1.3% versus 9.2%, P=0.039) whereas postoperative radiotherapy did not (7.1% versus 5.5%, P=0.63). CONCLUSION: Our study suggests that abnormal peritoneal cytology may be a prognostic factor for decreased survival in women with stage I-II endometrioid endometrial cancer, particularly for low-risk group.

Predictors for recurrent/persistent high-grade intraepithelial lesions and cervical stenosis after therapeutic conization: a retrospective analysis of 522 cases.

OBJECTIVE: The objective of the study is to identify the risk factors associated with recurrent/persistent disease and cervical stenosis after conization. METHODS: Five hundred twenty-two (522) cases of high-grade intraepithelial lesions treated by conization were retrospectively reviewed. Risk factors associated with recurrent/persistent disease were analyzed by univariate and multivariate analysis using a Cox hazard regression model. Factors that could potentially affect the risk of cervical stenosis were examined by univariate and by multivariate analysis using the χ 2 test and logistic regression, respectively. RESULTS: Recurrent/persistent diseases and cervical stenosis occurred in 4.8% and 5.4% of the patients, respectively. Age ≥46 years [hazard ratio (HR) 3.6, 95% CI 1.36-10.3, p = 0.0092] and surgical margin involvement (HR 13.44, 95% CI 5.07-46.37, p < 0.001) were independent predictors for recurrent/persistent diseases. Age ≥46 years [odds ratio (OR) 4.27, 95% CI 1.88-10.07, p < 0.001] and shortened interval after childbirth to conization (within 12 months) (OR 5.42, 95% CI 1.42-17.41, p = 0.016) were independent risk factors for cervical stenosis. CONCLUSION: Elderly patients (aged ≥46 years) are at high risk of recurrence and cervical stenosis, which may lead to unsatisfactory follow-up. Subsequent hysterectomy is beneficial to patients aged 46 or older with surgical margin involvement. Clinicians should recognize the possibility of cervical stenosis after conization during the breastfeeding period, leading to secondary infertility or hematometra.

Total laparoscopic hysterectomy for endometrial cancer in a renal transplantation patient receiving peritoneal dialysis: Case report and literature review.

Improved surgical techniques and immunosuppressant medications for organ transplantation have resulted in a significant increase in the number of women undergoing renal transplantation. Peritoneal dialysis (PD), a common supportive therapy for chronic renal failure, is also used in cases of renal transplantation failure. Herein, we report the first case of a rare total conventional laparoscopic gynecologic hysterectomy performed for endometrial cancer in a patient undergoing life-supportive PD as a result of renal transplantation failure. No unusual intraoperative complications were experienced, but post-surgical peritoneal leakage was observed. We reviewed the literature of alternative surgical methods of hysterectomy for endometrial cancer in patients who had undergone renal transplantation and were undergoing PD at the time of the hysterectomy. Laparoscopic hysterectomy could be safe in a renal transplantation patient receiving PD if injury to the transplanted ureter and renal artery is avoided by recognizing the patient's anatomy and PD leakage is averted by careful peritoneum suture and avoiding contact with the PD catheter.

Tumor Characteristics and Survival Outcome of Endometrial Cancer Arising in Adenomyosis: An Exploratory Analysis.

BACKGROUND: Endometrial cancer arising in adenomyosis (EC-AIA) is a rare entity of endometrial cancer, and its clinical significance has not been well studied. This study aimed to examine the tumor characteristics and survival outcomes of EC-AIA. METHODS: An exploratory analysis was performed to compare EC-AIA and historical control cases. For this study, EC-AIA cases were identified via a systematic literature search using PubMed/MEDLINE with entry keywords "endometrial cancer OR uterine cancer" AND "adenomyosis" (n = 46). The control group comprised consecutive non-EC-AIA cases from four institutions that had hysterectomy-based surgical staging (n = 1294). Patient demographics, pathology results, and survival outcomes were evaluated between the two groups. RESULTS: The EC-AIA group was significantly older than the control group (58.9 vs. 55.3 years; P = 0.032). In terms of tumor characteristics, 56.5% of the EC-AIA cases showed tumor within the myometrium without endometrial extension, and the EC-AIA group was significantly more likely to have tumors with more than 50% myometrial invasion (51.6 vs. 26.6%; P = 0.002) and serous/clear cell histology (22.2 vs. 8.2%, P = 0.002) while less likely to express estrogen receptor (14.3 vs. 84.6%; P < 0.001). Grade and stage distributions were similar (P > 0.05). In the univariate analysis, the EC-AIA group had a significantly poorer disease-free survival than the control group (5-year rate: 71.4 vs. 80.6%; P = 0.014). In the multivariate analysis, with control for age, ethnicity, histology, grade, and stage, EA-CIC remained an independent prognostic factor for decreased disease-free survival (adjusted hazard ratio, 3.07; 95% confidence interval 1.55-6.08; P = 0.001). CONCLUSIONS: The study suggested that endometrial cancer arising in adenomyosis may be an aggressive variant of endometrial cancer.