Efficacy of palonosetron plus dexamethasone in preventing chemotherapy-induced nausea and emesis in patients receiving carboplatin-based chemotherapy for gynecologic cancers: a phase II study by the West Japan Gynecologic Oncology Group (WJGOG 131).

OBJECTIVE: Palonosetron is effective for the management of acute and delayed chemotherapy-induced nausea and vomiting (CINV). While emetogenic carboplatin-based chemotherapy is widely used to treat gynecologic cancers, few studies have evaluated the antiemetic effectiveness of palonosetron in this setting. METHODS: A multicenter, single-arm, open-label phase II trial was conducted to evaluate the safety and effectiveness of palonosetron in controlling CINV in patients with gynecologic cancer. Chemotherapy-naïve patients received intravenous palonosetron (0.75 mg/body) and dexamethasone before the infusion of carboplatin-based chemotherapy on day 1. Dexamethasone was administered (orally or intravenously) on days 2-3. The incidence and severity of CINV were evaluated using the patient-completed Multinational Association of Supportive Care in Cancer Antiemesis Tool and treatment diaries. The primary endpoint was the proportion of patients experiencing complete control (CC) of vomiting, with "no rescue antiemetic medication" and "no clinically significant nausea" or "only mild nausea" in the delayed phase (24-120 hours post-chemotherapy). Secondary endpoints were the proportion of patients with a complete response (CR: "no vomiting" and "no rescue antiemetic medication") in the acute (0-24 hours), delayed (24-120 hours), and overall (0-120 hours) phases, and CC in the acute and overall phases. RESULTS: Efficacy was assessable in 77 of 80 patients recruited. In the acute and delayed phases, the CR rates the primary endpoint, were 71.4% and 59.7% and the CC rates, the secondary endpoint, were 97.4% and 96.1%, respectively. CONCLUSION: While palonosetron effectively controls acute CINV, additional antiemetic management is warranted in the delayed phase after carboplatin-based chemotherapy in gynecologic cancer patients (Trial registry at UMIN Clinical Trials Registry, UMIN000012806).

New diagnostic criteria of colposcopy for uterine cervix neoplasia.

AIM: The purpose of this study is to present alternative diagnostic criteria of colposcopy using new parameters. METHODS: Colposcopic photographs were reviewed in 1649 patients from the past 23 years, including 283 benign lesions, 327 low-grade squamous intraepithelial lesions (LSIL; cervical intraepithelial neoplasia 1), 549 high-grade squamous intraepithelial lesions (HSIL; cervical intraepithelial neoplasia 2/3), 78 microinvasive cancers, and 412 invasive cancers. Abnormal colposcopic findings were divided into: minor or major; single, or a combination of two or three findings; and under half or over half circumferential size. Histopathological backgrounds were investigated according to these new parameters of colposcopic findings. RESULTS: Minor abnormal colposcopic findings were observed in 21% of LSIL, and major abnormal findings were seen in 52% of LSIL, 86% of HSIL, and 86% of microinvasions. A single major abnormal finding was observed in 64% of the cases with LSIL, while two abnormal findings were observed in 43% of HSIL, and three abnormal findings were observed in 44% of microinvasions. In qualifying major abnormal colposcopic findings, under half size was detected in 91% of LSIL and 74% of HSIL, and over half size was observed in 58% of microinvasions. From these results, the following diagnostic criteria were instituted: (i) LSIL - single, minor or major findings and under half size; (ii) HSIL - two or three major findings and under half size; (iii) microinvasion - three major findings and over half size; and (iv) invasive cancer - irregular surface with atypical vessels. CONCLUSION: Our new diagnostic criteria of colposcopy are fully acceptable, based on their similar level of accuracy to cytology.

[Uterine cervical cancer screening in kitakyushu city: present and future].

Uterine cervical cancer is the most common primary gynecologic malignant tumor in Japan. Conventional cervical screening Papanicolaou (Pap) test has been shown to be extremely effective in reducing cervical cancer incidence and mortality, but the consultation rate for cancer screening in Japan is markedly low, at 20% of prescribed subjects, in comparison with other developed countries. In 2001, 15,501 women (6.8%) received a Pap test in Kitakyushu City, and that was less than half of national average. From 2009, free coupons for uterine cervical cancer screening were distributed to Japanese woman who were 20, 25, 30, 35 or 40 years of age as part of the project for women-specific cancer screening. The rate of participation in Pap testing was 22.3% in 2012, with 31,970 women receiving cervical tests. It was almost as high as the national level. It's obvious that high risk human papillomavirus (HPV) is responsible for cervical cancer incidence and HPV mainly infects through sexual practice. The rate of early cervical neoplasms and invasive cancers is currently increasing in young women. Abnormal Pap tests were detected in 2.3% of the women in 2008. To increase the population's participation in this screening process, a cost-effective and efficient system should be established. National and local governments, medical institutions, companies, and educational institutions must have an accurate understanding of the current situation, and take an assertive approach in order to decrease the mortality rate of uterine cervical cancer.

Trends in the demographic and clinicopathological characteristics in Japanese patients with endometrial cancer, 1990-2010.

OBJECTIVE: Over the past 20 years, the incidence of endometrial cancer has increased remarkably in Japan. The number of elderly females has also increased within the population of Japan. We examined the impact of advanced age on the demographic and clinicopathological characteristics in Japanese patients with endometrial cancer. METHODS: Data were collected from 319 surgically treated Japanese females with endometrial cancer from the files of the University Hospital of Occupational and Environmental Health, Yahatanishi-ku, Kitakyushu, Japan, between 1990 and 2010. χ(2) tests were performed to evaluate the trends in the variables between two decades (A: 116 cases from 1990-2000) and (B: 203 cases in 2001-2010). The histological subtypes were also evaluated based on the immunohistochemical expressions of p53, estrogen receptor, and Ki-67. RESULTS: The mean ages ± standard deviation in the decade A group and the decade B group were 57.5 years ± 9.7 years and 61.0 years ± 11.3 years, respectively (P < 0.02). There was an increase in the proportion of patients aged 70 years or older and of high-risk histological tumors including serous carcinoma, clear cell carcinoma, and carcinosarcoma (decade A group and decade B group: 9.5% vs 27.6%, P < 0.001, 10.4% vs 21.6%, P = 0.01, respectively), while the advanced surgical stage (III and IV), obesity (≥25 of body mass index), and nulliparity of the decade A group and decade B group were 23.3% vs 29.1%, P = 0.30, 28.4% vs 33.0%, P = 0.40, and 19.0% vs 21.2%, P = 0.66, respectively. The cancer-specific survival rates in the decade A group and the decade B group were 78.6% and 77.6%, respectively (P = 0.93). CONCLUSION: The increase in number of elderly females in the Japanese population is related to the increase in that of high-risk endometrial cancers. A study is needed to investigate prevention strategies and to improve the treatment of elderly patients with high-risk endometrial cancer.

Mitochondrial transcription factor A regulates BCL2L1 gene expression and is a prognostic factor in serous ovarian cancer.

Mitochondrial transcription factor A (mtTFA) is necessary for both transcription and maintenance of mitochondrial DNA (mtDNA). Recently, we reported that mtTFA is expressed not only in mitochondria, but also in nuclei. However, the function of mtTFA in the nucleus has not been clearly elucidated. In the present study, we examined nuclear mtTFA expression in 60 tissue samples of serous ovarian cancer using immunohistochemical analysis and found that 56.7% of serous ovarian cancer patients were positive for mtTFA, whereas 43.3% were negative. Univariate survival analysis showed that the overall 5-year survival rate was significantly worse for patients with mtTFA-positive cancer compared with mtTFA-negative cancer (32%vs 42%, respectively; P = 0.021). To elucidate the function of mtTFA in the nucleus, we investigated BCL2L1, a target gene of mtTFA. There was a significant correlation between nuclear mtTFA expression and BCL2L1 expression in seven ovarian cancer cell lines and in specimens of clinical ovarian cancer. Cellular BCL2L1 was downregulated following transfection of siRNA against mtTFA. BCL2L1 promoter activity was increased after transfection of mtTFA expression plasmid, but decreased after siRNA knockdown of mtTFA. Chromatin immunoprecipitation assays showed that mtTFA was bound to the BCL2L1 promoter region. These results suggest that mtTFA is a prognostic factor for a poor outcome of ovarian cancer and may function as an antiapoptotic factor, regulating genes such as BCL2L1. Furthermore, mtTFA may be a promising molecular target for novel therapeutic strategies for the treatment of ovarian cancer.

Expression of mitochondrial transcription factor A in endometrial carcinomas: clinicopathologic correlations and prognostic significance.

Mitochondrial transcription factor A (mtTFA) is necessary for both transcription and maintenance of mitochondrial DNA. This study was conducted to elucidate the clinicopathologic and prognostic significance of mtTFA in patients with endometrial carcinoma. This study investigated the relationship between the immunohistochemical expression of mtTFA and various clinicopathological variables in 276 endometrial carcinomas, including 245 endometrioid adenocarcinomas and 31 nonendometrioid carcinomas (21 serous carcinomas and 10 clear cell adenocarcinomas). Both uni- and multivariate regression analyses were performed. The mtTFA labeling index of endometrioid adenocarcinomas ranged from 0% to 98%, with a median value of 32%, which was selected as the cut-off point for mtTFA expression. The mtTFA expression in endometrioid adenocarcinomas was significantly associated with the surgical stage, myometrial invasion, lymphovascular space invasion, cervical invasion, and lymph node metastasis. In contrast, no correlation between clinicopathologic variables and mtTFA expression was found in nonendometrioid carcinomas. Correlation analysis between mtTFA and p53 expression by using the Pearson test showed significant correlation in endometrioid adenocarcinomas (P = 0.007), but no significant correlation in nonendometrioid carcinomas (P = 0.947). A univariate survival analysis showed that the 10-year overall survival rate of the patients with mtTFA-positive endometrioid adenocarcinoma was significantly worse than that of patients with mtTFA-negative endometrioid adenocarcinoma (80.8% vs. 93.8%, P = 0.012). However, the multivariate analysis revealed that mtTFA expression in endometrioid adenocarcinomas was no independent prognostic factor. The positive mtTFA expression is a useful maker for progression of the tumors and the poor prognosis of the patients in endometrioid adenocarcinomas.

[Uterine cervical cancer screening in Japan: today and future].

Despite the proven effectiveness of cytological uterine cervical cancer screening, the consultation rate for cancer screening in Japan is markedly low in comparison with other developed countries. Although the mortality of this cancer has been steadily decreasing, it has been on the rise in the recent several years. It is evident that human papillomavirus (HPV) is involved in the occurrence of uterine cervical cancer, and, because of changes in sexual awareness and the diversification of sexual behavior, the increase in the incidence of uterine cervical cancer, especially among young adults, has become a major social problem. There is a false negative rate of about 10% in cytological uterine cervical cancer screening, seen mostly in cervical adenocarcinoma cases. As there is a limit to the effectiveness of cancer screening by cytology alone, there is a movement in Japan to increase the accuracy of cytological screening by using liquid-based cytology (LBC) and adopting HPV testing. There are various problems in cytological cancer screening, but the national and local governments, medical institutions, companies, and educational institutions must have an accurate understanding of the current situation and take an assertive approach in order to decrease the mortality rate of uterine cervical cancer.

[The efficacy and safety of indisetron hydrochloride for the management of nausea/vomiting caused by chemotherapy for gynecologic cancer].

This clinical trial was designed to evaluate the efficacy and safety of indisetron hydrochloride an oral 5-HT3 receptor antagonist, for the management of nausea/vomiting caused by chemotherapy for gynecologic cancer with paclitaxel/ carboplatin or docetaxel/carboplatin. Indisetron hydrochloride(8 mg)was administered orally to 46 gynecologic cancer patients at 0.5 hours before administration of the above chemotherapy agents. Number of patients who showed nausea or vomiting for 24 hours was counted. The complete vomiting inhibition rate at 24 hours after chemotherapy was 89.1%(41/46), and nausea inhibition rate was 71.7%(33/46). No serious adverse events were observed. These findings indicate that prophylactic administration of indisetron hydrochloride is safe and useful for inhibition of nausea/vomiting caused by cancer chemotherapy.

Evaluation of pregnancy-related cells in endometrial cytology.

OBJECTIVE: To determine the significance of pregnancy-related cells in endometrial smears. STUDY DESIGN: Pregnancy-related cells in 4429 endometrial smear samples were retrospectively analyzed and evaluated for clinicopathologic and cytomorphologic features. RESULTS: Of the 4429 endometrial smears taken for cancer screening, pregnancy-related cells were detected in 12 cases (0.3%). They were estimated cytologically as negative or suspicious and confirmed as cases ofspontaneous abortion (8 cases), placental site nodule (3 cases), and partial hydatidiform mole (1 case). Decidual cells were observed in all cases, and some of these showed atypia. Trophoblasts were observed in 5 (41.7%) of the 12 cases. Syncytiotrophoblasts were observed in 1 case (8.3%) and nonsyncytiotrophoblasts in 5 (41.7%) of the 12 cases. Pregnancy-related cells were observed in an endometrial smear in 7 cases; other cases were missed during cytologic examination and were retrospectively identified. CONCLUSION: Pregnancy-related cells are likely to be missed because they are difficult to identify or are surrounded by a cluster of endometrial cells. The decidual cell is a key cell for the cytologic diagnosis of pregnancy-related cells. Determining the existence of pregnancy-related cells in endometrial smears is important for the further assessment of patients and the differential diagnosis of several endometrial lesions.

Myxoid leiomyosarcoma of the uterus with subsequent pregnancy and delivery.

BACKGROUND: Myxoid leiomyosarcoma of the uterus is an extremely rare neoplasm. In young women with this disease, fertility should be considered in the treatment protocol. CASE: A 20-year-old woman presented with a huge pelvic mass originating from the uterine wall and showing a histopathology of myxoid leiomyosarcoma. Five and one-half years after laparotomy, the recurrent tumor was found and removed. Two years after the second operation, she became pregnant, and delivered a healthy baby by cesarean section. Multiple recurrent masses were evident and removed at cesarean section. She is alive and well without evidence of recurrence 1 year after delivery. CONCLUSION: The best treatment for this tumor is not established. In young women with a desire to bear children, the management is more controversial.