Cervical cancer screening rates before and after the Great East Japan Earthquake in the Miyagi Prefecture, Japan.

After disasters, issues pertaining to women's health such as irregular periods and bleeding are well surveyed. However, the management of women's health, especially changes in the rate of health checkups, has not been investigated. In the present study, we focused on the change in the cervical cancer screening rates (CCS-Rs) before and after the Great East Japan Earthquake in Miyagi Prefecture, Japan. The earthquake had a magnitude of 9.0, a profound disaster. We examined the CCS-R from 2009 to 2016 in 45 areas of the Miyagi Prefecture. Screening was completed using mobile vans. In the 4 areas impacted by the tsunami after the earthquake, a marked decrease in the CCS-R was observed in 2011 when the earthquake took place (more than a 3% decrease compared with that in the previous year). The CCS-Rs in these 4 regions remained lower in 2016 than in the previous year. In 2009-2016 except for 2014, CCS-Rs in coastal areas (9 areas) were significantly lower than those in the non-coastal areas (36 areas). A delay in seeking healthcare, also known as "patient's delay," is considered as one of the problems of cancer treatment in affected areas. It is possible that a decrease in the CCS-R may lead to low detection of advanced stages of cancer. Therefore, the establishment of a comprehensive medical system including medical screening after a disaster is important for the management of women's health.

Lower Incidence of Cervical Intraepithelial Neoplasia among Young Women with Human Papillomavirus Vaccination in Miyagi, Japan.

The Japanese national immunization programme for Human Papillomavirus (HPV) started in 2010. Vaccination rates increased up to 70% in women in the 1996-1999 birth. However, the proactive recommendation for HPV vaccine was suspended in 2013, following repeated media reports of adverse events. Vaccination rates plumped to less than 1% in women born since 2002. In this study, incidence of abnormal cytology and histology was examined in terms of HPV vaccination among 5,924 women aged 20 to 24 years in the fiscal year (FY) 2014 and 2015. The total rate of vaccination was 16.9% (1,002/5,924). In case of FY 2015, the rates of vaccination were 59.26%, 49.68%, 11.97%, 9.08%, and 4.58% in those aged 20, 21, 22, 23, and 24 years old, respectively. The rates of high-grade squamous intraepithelial lesion (HSIL) or worse were 0.20% (2/1,002) in women with HPV vaccination and 1.14% (56/4,922) in those without HPV vaccination, indicating a significant reduction of 82.46% with vaccination (P < 0.0001). The rates of cervical intraepithelial neoplasia (CIN) 1+ were 0.80% (8/1,002) in women with vaccination and 2.28% (112/4,922) in those without vaccination. The reduction rate of CIN1+ was 64.91% (P = 0.0025). The rates of CIN2+ were 0.10% (1/1,002) with vaccination and 0.69% (34/4,922) without vaccination. The reduction rate of CIN2+ was 85.51% (P = 0.0261). Our data are the first to demonstrate a significant reduction of CIN2+ cases in an Asian population. Scientific discussion is needed to restart the proactive recommendation for HPV vaccine in Japan.

Beneficial Effects of Human Papillomavirus Vaccine for Prevention of Cervical Abnormalities in Miyagi, Japan.

Prevention of cervical cancer has been unsuccessful in Japan because of low rates of cancer screening and vaccination. The Vaccine Adverse Review Committee of the Japanese Government investigated 2,475 adverse events and reported 617 (6.9/100,000) severe cases and 176 (2.0/100,000) cases with chronic pain. The proactive recommendation for human papillomavirus (HPV) vaccination has been suspended since June 2013. In this study, we examined vaccination rate and incidence of abnormal cervical cytology in women aged 20 to 24 years attending cancer screening in Miyagi. Among the 3,272 women who underwent a health check in the fiscal year 2014 (April 2014-March 2015), 332 (10.2%) received a HPV vaccination. The HPV vaccination rates were 42.3%, 10%, 17.5%, 3.8% and 4.0% in women aged 20, 21, 22, 23 and 24 years, respectively. The rates of atypical squamous cells of undetermined significance (ASC-US) or worse were 2.41% (8/332) in women with HPV vaccination and 5.03% (148/2,940) in those without HPV vaccination, indicating a significant decrease in vaccinated women (p = 0.03). ASC-US cases were referred to HPV DNA tests. In addition, the rates of high grade squamous intraepithelial lesion (HSIL) or worse were 0.30% (1/332) in women with HPV vaccination and 0.82% (24/2,940) in those without HPV vaccination, showing the marginal decrease in women who were vaccinated (p = 0.3). Thus, this study indicates that HPV vaccination is associated with a reduction in the incidence of cervical abnormalities, suggesting a need for scientific discussion of reinstatement of proactive recommendation for HPV vaccine in Japan.

A Multi-Institutional Feasibility Study on the Use of Automated Screening Systems for Quality Control Rescreening of Cervical Cytology.

OBJECTIVE: To evaluate the efficacy of the automated screening system FocalPoint for cervical cytology quality control (QC) rescreening. False-negative rates (FNRs) were evaluated by a multi-institutional retrospective study. STUDY DESIGN: Cervical cytology slides that had already been reported as negative for intraepithelial lesion or malignancy (NILM) were chosen arbitrarily for FocalPoint rescreening. Slides stratified into the highest 15% probability of being abnormal were rescreened by a cytotechnologist. The slides that were abnormal were reevaluated by a cytopathologist to be false negatives. RESULTS: Rescreening of 12,000 slides, i.e. 9,000 conventional slides and 3,000 liquid-based cytology (LBC) slides, was performed; 9,826 (7,393 conventional and 2,433 LBC) were satisfactory for FocalPoint (2,174 were determined unsatisfactory) and those within the highest 15% of probability (1,496, i.e. 1,123 conventional and 373 LBC) were rescreened. As a result, 117 (96 conventional and 21 LBC) were determined as abnormal (other than NILM) and the FNR was 1.19%. Among these 117 slides, 40 (35 conventional and 5 LBC) were determined as high-grade squamous intraepithelial lesion and greater (HSIL+). CONCLUSION: Of 117 (1.19%) abnormal slides detected, 40 (0.41%) were determined to be HSIL+. This result suggests that FocalPoint is effective for QC rescreening of cervical cytology.

Challenges in breast and cervical cancer control in Japan.

Since the mid-1990s, there has been an increasing incidence of, and mortality from, cervical and breast cancers in Japan. Such an increase has raised concerns over the efficiency of Japan's screening programmes for these cancers. Although citizens benefit from universal health coverage, the Japanese health insurance system mostly focuses on tertiary prevention and disease treatment, while secondary prevention (screening) is low priority. Citizens have multiple opportunities to be screened for cancer-either through programmes organised by municipalities, or individual or collective, opportunistic and comprehensive health check-ups on a voluntary basis. Despite this, however, participation is as low as 35% of the target population for both cancers. In this Policy Review, we discuss the challenges in the prevention of breast and cervical cancers in Japan, particularly focusing on the structure of the National Health Insurance system and the National Cancer Control Plan, reasons for low participation as a result of social and political attitudes, as well as providing recommendations to overcome these challenges. Japanese women would benefit from new measures to increase participation, a national data surveillance programme to monitor screening activities, and the implementation of a quality assurance system among all providers.

Clinical efficacy of nedaplatin-based concurrent chemoradiotherapy for uterine cervical cancer: a Tohoku Gynecologic Cancer Unit Study.

OBJECTIVE: The aim of this study was to compare the efficacy of nedaplatin-based concurrent chemoradiotherapy (CCRT) with that of cisplatin-based CCRT in patients with cervical cancer. METHODS: The medical records of patients with cervical cancer who had undergone CCRT between 2003 and 2007 were retrospectively reviewed. Of these, 129 patients were treated postoperatively with CCRT (n = 52) or primary CCRT (n = 77). A total of 29 patients were treated with nedaplatin-based postoperative CCRT and 23 patients were treated with cisplatin-based postoperative CCRT. A total of 28 patients were treated with nedaplatin-based postoperative CCRT, and 49 patients were treated with cisplatin-based postoperative CCRT. Progression-free survival (PFS) and overall survival (OS) were compared between the treatment groups. RESULTS: With postoperative CCRT, there were no significant differences in recurrence rate (P = 1.0000), PFS (log-rank: P = 0.8503), and OS (log-rank: P = 0.8926) between the two treatment groups. With primary CCRT, there were no significant differences in PFS (log-rank: P = 0.7845) and OS (log-rank: P = 0.3659). The frequency of acute toxicity was not significantly different between the cisplatin-based postoperative CCRT group and the nedaplatin-based postoperative CCRT group. CONCLUSIONS: Nedaplatin-based postoperative CCRT is an effective and well-tolerated regimen for both early-stage and advanced-stage cervical cancer patients.

Investigation of the clinicopathological features of squamous cell carcinoma of the vulva: a retrospective survey of the Tohoku Gynecologic Cancer Unit.

BACKGROUND: This multi-institutional study was conducted to clarify the clinicopathological features of squamous cell carcinomas of the vulva. METHODS: The medical records of vulvar cancer patients treated between 2002 and 2012 were retrospectively reviewed following approval by the Institutional Review Board of each institution. RESULTS: One hundred and eleven patients with vulvar malignancies were included. Of these, 63 patients had squamous cell carcinoma (57 %). Initial treatment was surgery, radiation therapy (RT), and concurrent chemoradiotherapy (CCRT) in 34 (54 %), 15 (24 %), and 11 (17 %) patients, respectively. Nineteen, 11, 26, and 7 patients had stage I, II, III, and IV disease, respectively. Of the 34 patients who had surgical treatment, 50 % had stage I disease, while 74 % of those who received CCRT had stage III or IV disease. Complete response (CR) rates for the surgery, RT, and CCRT groups were 73, 60, and 64 %, respectively. The 5-year survival rates for stage I/II and III/IV disease were 64 and 39 %, respectively (P = 0.019). The 5-year survival rates for the surgery, RT, and CCRT groups were 53, 38, and 50 %, respectively, and the prognosis of patients treated with surgery or CCRT was significantly better than that of patients who received RT (P < 0.05). In multivariate analysis, clinical response to initial treatment was an independent prognostic factor (P < 0.001). CONCLUSIONS: Although many patients had advanced-stage disease in the CCRT group, the therapeutic outcome for the surgery and CCRT groups was similar. Thus, CCRT may be a promising treatment for squamous cell carcinoma of the vulva.

Evaluation of postoperative chemotherapy in patients with uterine carcinosarcoma: a retrospective survey of the Tohoku Gynecologic Cancer Unit.

BACKGROUND: The aim of this study was to evaluate prognostic factors including efficacy of postoperative chemotherapy in Japanese patients with uterine carcinosarcoma. METHODS: We conducted a retrospective survey of seven medical facilities in the Tohoku Gynecologic Cancer Unit. RESULTS: A total of 45 patients who had undergone hysterectomy and bilateral salpingo-oophorectomy were enrolled. No significant difference was observed in overall survival according to patient age (≤ 50 years vs >50 years) or retroperitoneal lymphadenectomy (performed vs. not performed). However, the International Federation of Gynecology and Obstetrics stage (stage I/II vs stage III/IV) and postoperative chemotherapy (provided vs not provided) were significant prognostic factors in both univariate and multivariate analyses for the 25-month median follow-up period. CONCLUSIONS: Our results revealed that postoperative chemotherapy should be considered for all uterine carcinosarcoma stages in Japanese patients.

Gastric-type endocervical glandular neoplasms associated with aberrant p16 expression and K-RAS gene mutation in Peutz-Jeghers syndrome.

In this report, unique endocervical glandular lesions exhibiting gastric differentiation were examined in a patient with Peutz-Jeghers syndrome. The result of the human papillomavirus (HPV) in situ hybridization (ISH) for the hysterectomy specimens was negative, but they demonstrated a papillary mucinous adenocarcinoma at the proximal endocervix continuous to atypical lobular endocervical glandular hyperplasia. Both contained MUC6-positive neutral mucin in cytoplasm, and showed different immunoreactivity to p16, Ki-67, and p53. Moreover, they harbored the identical K-RAS gene mutation suggesting that there was a common origin. Somatic K-RAS mutation and defective function of p16 may have been involved in the tumorigenesis of these unusual mucinous neoplasms.

Redistribution of resistance and sensitivity to platinum during the observation period following treatment of epithelial ovarian cancer.

The standard postoperative chemotherapy for epithelial ovarian cancer is a combination therapy including platinum and taxanes. The aim this study was to investigate the degree of platinum sensitivity in patients with relapsed epithelial ovarian cancer according to the treatment-free interval (TFI) and the histological tumor type. The medical records of 405 patients diagnosed with stage III/IV ovarian cancer, including 107 patients who relapsed after attaining a clinical complete response with first-line treatment, were retrospectively reviewed. The degree of platinum sensitivity was assessed by comparing the progression-free survival (PFS) following the second-line treatment. In patients with serous/endometrioid adenocarcinoma who were treated with platinum following relapse, there were significant differences in the PFS between the following groups of patients: those who relapsed within 6 months and those who relapsed between 6 and 12 months; those who relapsed between 6 and 12 months and those who relapsed between 12 and 18 months; and those who relapsed between 12 and 18 months and those who relapsed after 18 months. By contrast, in patients with clear cell/mucinous adenocarcinoma who were treated with platinum following a relapse, there were no significant differences in the PFS between patients who relapsed within 6 months and those who relapsed between 6 and 12 months, while there were significant differences in the PFS between those who relapsed between 6 and 12 months and those who relapsed after 12 months. With regard to the patients who relapsed after 12 months, the PFS of those with clear cell/mucinous adenocarcinoma was significantly shorter compared with the PFS of those with serous/endometrioid adenocarcinoma. Therefore, we considered it justified to classify patients with clear cell/mucinous adenocarcinoma who relapsed within 12 months as platinum-resistant and those who relapsed after 12 months as platinum-sensitive.

Paclitaxel-carboplatin for advanced or recurrent carcinosarcoma of the uterus: the Japan Uterine Sarcoma Group and Tohoku Gynecologic Cancer Unit Study.

BACKGROUND: Paclitaxel and carboplatin (PC) have shown antitumor activity in carcinosarcoma of the uterus (CS). The purpose of this prospective multi-institutional study was to determine the response rate (RR), progression-free survival (PFS) and overall survival (OS) and to assess the toxicity of paclitaxel and carboplatin in patients with CS. METHODS: We conducted a phase II study in which patients were administered paclitaxel 175 mg/m(2) over a 3-h period followed by carboplatin (area under the serum concentration-time curve = 6) intravenously over a 30-min period on day 1 of each treatment cycle (3 weeks) until disease progression or adverse effects prohibited further therapy. Eligible patients had histologically confirmed, advanced stage (III or IV), persistent or recurrent measurable disease, and no prior chemotherapy. RESULTS: Six patients were enrolled between February 2006 and April 2009. The median age of the patients was 61 (range 48-77) years; one patient was stage IIIC (17 %) and five were stage IVB (83 %). Three patients (50 %) (1 at stage IIIC and 2 at stage IVB) received total abdominal hysterectomy plus bilateral salpingo-oophorectomy as part of the initial treatment; five (83 %) had homologous tumors and one (17 %) had a heterologous tumor. The median cycle number administered was 4.8 (range 2-7). The RR was 66.7 % (complete response, 2; partial response, 2); the PFS was 9.1 months and OS was not reached. The frequently observed Grade 4 toxicities were neutropenia (3 patients, 50 %). Manageable neutropenic sepsis developed in one patient. CONCLUSION: This is the first prospective multi-institutional study in Asia showing that PC may be effective and tolerable for the treatment of advanced or recurrent CS.

Yolk sac tumor of the ovary: a retrospective multicenter study of 33 Japanese women by Tohoku Gynecologic Cancer Unit (TGCU).

Yolk sac tumor (YST) of the ovary is a rare germ cell tumor comprising about 1% of all ovarian malignancies. YST usually occurs as a rapidly growing unilateral tumor in young women. With the introduction of cisplatin, YST has been changed from a fatal tumor to a curable tumor. The standard treatment of YST consists of fertility-preserving surgery and 3 or 4 courses of adjuvant combination chemotherapy with bleomycin, etoposide, and cisplatin (BEP). However, the long-term prognosis of BEP-treated YST patients has not been well studied. We therefore conducted a retrospective multicenter study to investigate the prognostic factors of 33 YST patients, including 25 patients treated with BEP. The median age at initial treatment was 20 years (range 10-53). There were 15 patients (at stage I), one (stage II), 16 (stage III), and one (stage IV). Nominal and grouped numerical values were analyzed by the Kaplan-Meier method. All patients had unilateral tumor, with right-side predominance (23 patients; P = 0.02). Eighteen patients had pure YST, 13 had mixed germ cell tumor with YST component, and other 2 patients were not specified. Twenty-eight patients received fertility-preserving surgery. Twenty-seven patients had optimal surgery with less than 1 cm residual tumor diameter. Median number of chemotherapy courses was 5. Median follow-up period was 49 months. The cumulative 5-year survival rate was 87%. Univariate analysis revealed the following significant prognostic factors (P < 0.05): stage, tumor diameter, and residual tumor. Extensive debulking surgery to minimize residual tumor would improve the prognosis.

Investigation of the clinicopathological features of fallopian tube malignancy.

The present study investigated the clinico-pathological features of fallopian tube malignancy (FTM) and elucidated the biological behavior of this disorder. Data were compiled concerning FTM from 68 patients from 7 institutes. The patients included 60 cases with fallopian tube carcinoma and 8 cases with fallopian tube carcinosarcoma. The clinical stage was stage III or higher in 72% of the cases. A complete response or partial response was achieved in 56 and 10 of the 68 patients with FTM, respectively, indicating a response rate of 97.1%. The median observation period for FTM was 41 months (3 to 126 months). Three of the 19 patients with stage I/II disease (16%) and 31 of the 49 patients with stage III/IV disease (63%) experienced recurrence, with a median progression-free survival of 17.5 months, and a 3-year overall survival of 77.2%. Regarding the site of recurrence, local intraperitoneal recurrence (26.2%) and solitary recurrences in lymph nodes (19.0%) and in the liver (16.7%) were relatively frequent. Secondary debulking surgery (SDS) was performed in 15 patients (44%) out of the 34 recurrent FTMs. Conversely, recurrence was associated with ascites (carcinomatous peritonitis) in 4 of the 34 recurrent patients, but all 4 patients died. The median survival period after recurrence was 28 months: 7.5 and 30 months with and without ascites, respectively (P<0.001). A univariate analysis showed that prognosis was significantly correlated only with whether SDS could be performed. These results suggest that since FTM frequently results in solitary recurrence, aggressive recurrence treatment including SDS could improve prognosis.

Phase II clinical study of the combination chemotherapy regimen of irinotecan plus oral etoposide for the treatment of recurrent ovarian cancer (Tohoku Gynecologic Cancer Unit 101 Group Study).

OBJECTIVE: To evaluate the efficacy and safety of the combination chemotherapy regimen of irinotecan plus oral etoposide for the treatment of patients with recurrent ovarian cancer after previous treatment with platinum and taxane agents. PATIENTS AND METHODS: A total of 42 patients with recurrent ovarian cancer who had an evaluable lesion and provided informed consent for participation in the present study were analyzed. Irinotecan was administered intravenously at a dose of 60 mg/m on days 1 and 15. Etoposide was administered orally at a daily dose of 50 mg/body weight from days 1 to 21. A 28-day period comprised one cycle. The tumor response, adverse events, progression-free survival, and overall survival were examined. Tumor response was evaluated based on the Response Evaluation Criteria in Solid Tumors and the serum CA125 levels (Gynecologic Cancer Intergroup criteria). Adverse events were assessed according to the NCI-CTCAE (version 3.0). RESULTS: Partial response was observed in 21 patients, stable disease in 14 patients, and progressive disease in 7 patients. The response rate was 50.0%, and the clinical benefit (partial response + stable disease) rate was 83.3%. Hematological toxicities of at least grade 3 severity included leukopenia in 21 patients (50.0%), neutropenia in 22 patients (52.4%), thrombocytopenia in 1 patient (2.4%), anemia in 9 patients (21.4%), and febrile neutropenia in 3 patients (7.1%). Nonhematological toxicities of at least grade 3 severity included queasy feeling in 5 patients (11.9%), vomiting in 3 patients (7.1%), and diarrhea in 2 patients (4.8%). Acute myeloid leukemia occurred in one patient (2.4%). CONCLUSIONS: It is suggested that combination chemotherapy with irinotecan plus oral etoposide offers significant clinical benefit to patients with recurrent ovarian cancer previously treated with platinum and taxane agents.

Malignant transformation arising from mature cystic teratoma of the ovary: a retrospective study of 20 cases.

OBJECTIVES: Mature cystic teratoma (MCT) of the ovary rarely undergoes malignant transformation (MT). Malignant transformation carries a significantly worse prognosis than epithelial ovarian cancer, regardless of whether postoperative chemotherapy or radiotherapy is applied. The rarity of this tumor has posed a significant challenge to developing standardized postoperative management protocols. The aim of this study was to review our experience with MT and to describe our current treatment practices. METHODS: A retrospective chart review of these patients was performed that identified 20 women treated for MT of MCT at our centers between 1988 and 2008. RESULTS: The median age was 52.5 (range, 29-77) years. Fifteen patients had squamous cell carcinoma (SCC), and 5 patients had other histological subtypes. The International Federation of Gynecology and Obstetrics stage distribution was as follows: 11 were stage I, 4 were stage II, 4 were stage III, and 1 was stage IV. All patients underwent an initial laparotomy. Eleven patients received adjuvant treatment: 8 were treated with chemotherapy, 2 with concurrent chemoradiation therapy, and 1 with radiation therapy. Platinum-based chemotherapy was the first-line regimen. The overall 1-year survival rate was 70%. Significant correlations between overall survival and age, stage, and residual tumor were presented (P = 0.044, P = 0.0107, P < 0.0001, respectively). Eight patients with advanced stage died of their disease. Four patients, however, were treated with adjuvant chemotherapy or concurrent chemoradiation therapy and survived more than 1 year. One stage III patient had a disease-free interval of 2 years. Two cases of SCC treated with combination platinum/taxane chemotherapy temporarily responded. In the other 2 cases of SCC, concurrent chemoradiation therapy with nedaplatin also resulted in tumor regression. CONCLUSIONS: The prognosis of MT is highly dependent on age, stage, and optimal cytoreduction. Adjuvant treatment has not been standardized, although our experience supports the use of combination platinum/taxane chemotherapy.

Case-control study of green tea consumption and the risk of endometrial endometrioid adenocarcinoma.

OBJECTIVE: To investigate the association between green tea consumption and the risk of endometrial cancer restricted to endometrial endometrioid adenocarcinoma (EEA) using a case-control design in Japan. METHODS: The cases were 152 patients with histopathologically diagnosed EEA, and the controls were 285 healthy women who were matched for age and area of residence with individual cases. The subjects completed a questionnaire regarding health-related lifestyle and reproductive history, and a food frequency questionnaire. Odds ratios (ORs) of EEA for frequency of green tea consumption were calculated by conditional logistic regression analysis. RESULTS: We observed a significant inverse association between green tea consumption and the risk of EEA with a dose-response relationship. The multivariate-adjusted OR of EEA was 0.77 (95% CI: 0.37-1.58) for those in the second quartile of green tea consumption (5-6 cups/week-1 cup/day), 0.61 (0.30-1.23) in the third quartile (2-3 cups/day), and 0.33 (0.15-0.75) in the highest quartile (> or = 4 cups/day), as referenced with those in the lowest quartile (< or = 4 cups/week; p for trend = 0.007). This inverse association was consistently observed regardless of the presence or absence of factors such as obesity and menopause. CONCLUSION: Green tea consumption may be associated with a lower risk of EEA.

Smoking, earlier menarche and low parity as independent risk factors for gynecologic cancers in Japanese: a case-control study.

During recent decades, the incidence of gynecologic cancers, i.e., cancers of the cervix, endometrium and ovary, has increased in Japan. However, risk factors of gynecologic cancers have not been fully clarified in Japan. To investigate common and site-specific risk factors among gynecologic cancers, we conducted a hospital-based case-control study. The cases, i.e., 151 cervical, 103 endometrial and 141 ovarian cancer cases and the controls (n = 2016) were selected from female patients aged 30 and over, who were admitted to a single hospital in Miyagi Prefecture from 1997 to 2003. Information on reproductive factors, exogenous hormone use, and lifestyles including smoking was collected using a self-administered questionnaire. Smoking was significantly associated with an increased risk of cervical cancer. A dose-response relationship with the number of cigarettes per day was also observed (p for trend = 0.004). Older age at menarche was associated with a decreased risk of endometrial and ovarian cancers. For these cancers, the decreased risk was detected with increasing parity number (endometrium, p for trend = 0.0001; ovary, p = 0.0002). There was no significant association between exogenous hormone use and gynecologic cancer risk. The results indicate that smoking is a major risk factor of cervical cancer. In addition, hormonal factors, which are related to early onset of menarche and low parity, are common risk factors for endometrial and ovarian cancers. The increase in female smokers and the decrease in fertility rate may contribute to the increase in gynecologic cancer incidence in Japan.

Case-control study of coffee consumption and the risk of endometrial endometrioid adenocarcinoma.

This study examined the association between coffee consumption and the risk of endometrial endometrioid adenocarcinoma (EEA) in Japan by a case-control design. The cases consisted of 107 women less than 80 years of age from two medical centers who had been histopathologically diagnosed to have EEA. The controls, selected from the participants of a cancer-screening program, were 214 women, with two controls selected for each case (matched for age and for area of residence). A self-administered questionnaire containing questions to determine dietary and beverage consumption, as well as reproductive history, was distributed to the cases and controls. Conditional logistic regression analysis was used to estimate the odds ratio (OR) of EEA for three levels of coffee consumption with adjustment for potential confounding factors. The multivariate-adjusted OR of EEA for individuals in the highest tertile of coffee consumption (2 to 3 cups or more/day) was 0.4 [95% confidence interval (CI), 0.2-0.9], and that of cases in the intermediate tertile (5 to 6 times/week-1 cup/day) was 0.6 (95% CI, 0.3-1.2), relative to the individuals in the lowest tertile of coffee consumption (3 to 4 times or less/week) (P for trend=0.014). The above association was observed in postmenopausal women (P for trend=0.016), but not in premenopausal women (P for trend=0.90). This study thus revealed an inverse dose-response relationship between coffee consumption and the risk of EEA, and its strong association in postmenopausal women but not in premenopausal women.

A phase II multicenter trial of concurrent chemoradiotherapy with weekly nedaplatin in advanced uterine cervical carcinoma: Tohoku Gynecologic Cancer Unit Study.

The purpose of this study was to evaluate the effectiveness and safety of concurrent chemoradiotherapy using weekly nedaplatin for the treatment of locally advanced squamous cell carcinoma of the uterine cervix. Nedaplatin at 30 mg/m(2) was administered weekly 6 times with a concurrent external beam and intracavity radiotherapy. External beam radiation was delivered with a fraction dose of 2 Gy per day for 5 days a week during a 5-week period and intracavitary brachytherapy, of which the fraction size is 6 Gy to point A, was given once a week for a total of 4 times using a remote after-loading system. Forty-five patients were enrolled in this trial between April 2003 and December 2006. Of the 45 patients, 40 (88.9%) completed the scheduled treatment and were evaluated for efficacy and safety. Of these, 4 were stage Ib2, 12 were stage IIb, 18 were stage IIIb and 6 were stage IVa. The age distribution ranged from 27 to 79 years with a median age of 58. The 40 patients achieved an objective response, 36 (90%) a complete response and 4 (10%) a partial response. At a median follow-up of 29 months (range, 8-52), the 3-year progression-free and overall survival were 58.7% (95% confidence interval, 42-75%) and 78.0% (95% confidence interval, 56-90.0%), respectively. Acute toxicities were transient and rendered non-lethal. Of the 45 patients enrolled for the trial, only 3 (6.7%) had grade 4 leukopenia and neutropenia, respectively. Grade 3 diarrhea and nausea/ vomiting were observed in 2 (4.4%) and 1 (2.2%), respectively. These results indicate that weekly nedaplatin of 30 mg/m(2) with concurrent radiotherapy is an effective and well-tolerated regimen for advanced squamous cell carcinoma of the uterine cervix.

Prognoses and prognostic factors of carcinosarcoma, endometrial stromal sarcoma and uterine leiomyosarcoma: a comparison with uterine endometrial adenocarcinoma.

AIMS: The aims of this study were to evaluate the factors affecting prognosis in patients with uterine sarcomas and to demonstrate that carcinosarcoma bears a similarity to high-grade endometrial carcinoma in terms of its prognosis and clinicopathological parameters. METHODS: In June 2004, 17 Japanese institutions received questionnaires regarding uterine sarcomas. Study patients had uterine sarcomas initially treated at each institution between January 1990 and May 2004. Survival analyses and comparisons were performed by univariate methods. Patient data of 921 cases of endometrial adenocarcinoma were also analyzed and compared to the data with the uterine sarcomas. RESULTS: One hundred twenty-one patients with uterine sarcomas were identified who met study eligibility criteria. In uterine sarcomas, carcinosarcoma had a worse prognosis than other sarcomas, but the difference was not significant (p = 0.302). In carcinosarcoma, significant differences were observed with age (p = 0.0388), stage (p < 0.01) and surgical procedure (with or without pelvic lymphadenectomy, p = 0.0316). In carcinosarcoma and G3 adenocarcinoma, no significant difference was identified with regard to overall survival in univariate (p = 0.191) and multivariate (p = 0.168) analyses. CONCLUSION: Our results demonstrate that the clinical behavior of carcinosarcoma strongly resembles that of G3 endometrial adenocarcinoma, setting it apart from other 'pure' uterine sarcomas.