Awareness of Infectious Disease Screening During Early Pregnancy and Knowledge About its Vertical Transmission in Japan: A Report from the Pregnant Women Health Initiative.

OBJECTIVES: We aimed to clarify the accuracy of pregnant women's knowledge and understanding regarding infectious disease screening in early pregnancy and clarify the roles that should be played by health care providers in promoting the health of pregnant women and their children. METHODS: A cross-sectional questionnaire survey was conducted in 25 hospitals across Japan from May 2018 to September 2019. We compared the agreement rates regarding screening results for hepatitis B virus (HBV), hepatitis C virus (HCV), syphilis, human T-cell leukemia virus-1 (HTLV-1), and cervical cytology in the medical records and understanding of their results by pregnant women. We then investigated whether participants had knowledge regarding the risk of mother-to child transmission in these diseases and factors associated with their knowledge. RESULTS: We enrolled 2,838 respondents in this study. The rates of agreement for HBV and cervical cancer screening related to human papillomavirus infection were "substantial," those for syphilis was "moderate," and those for HCV and HTLV-1 were "fair," according to the Kappa coefficient. The rate of knowledge regarding mother-to-child transmission of syphilis was highest (37.0%); this rate for the other items was approximately 30%. Increased knowledge was associated with higher educational level and higher annual income. CONCLUSIONS FOR PRACTICE: Pregnant women in Japan had generally good levels of understanding regarding their results in early-pregnancy infectious disease screening. However, they had insufficient knowledge regarding mother-to-child transmission of these diseases. Health care providers should raise awareness in infectious disease prevention among pregnant women and the general public, providing appropriate measures and implementing effective perinatal checkups and follow-ups for infectious diseases.

Does the extension of the type of hysterectomy contribute to the local control of endometrial cancer?

OBJECTIVE: To examine the necessity and sufficiency of different types of hysterectomy for the surgical treatment of endometrial cancer. METHODS: This was a multicenter collaborative study conducted by 11 institutions. Among patients with stage I-III endometrial cancer who underwent surgery as the initial treatment (only chemotherapy was provided if adjuvant therapy was needed) from 2001 to 2012, we retrospectively examined the type of hysterectomy, clinicopathological factors, recurrence rate over a maximum period of 5 years, and the site of recurrence. The local recurrence rate was examined by univariate and multivariate analyses. RESULTS: Among 1335 patients, 982 (73.6%) underwent simple hysterectomy (SH) and 353 (26.4%) underwent modified radical hysterectomy (mRH) and were observed for a mean duration of 51.8 months. No significant difference was observed in the rate of local recurrence between the SH and mRH groups (p = 0.928). In multivariate analysis, clinicopathological factors independently associated with localized recurrence included postmenopausal status [hazard ratio (HR) 5.036, 95% confidence interval (CI) 1.506-16.841, p = 0.009], with stages II (HR 3.337, 95% CI 1.701-6.547, p < 0.001) and III (HR 2.445, 95% CI 1.280-4.668, p = 0.007), vs stage I and histological type 2 (HR 1.610, 95% CI 0.938-2.762, p = 0.001). CONCLUSIONS: For endometrial cancer patients requiring surgery, the selection of a more extensive type of hysterectomy did not reduce the rate of local recurrence. Therefore, there is little significance in performing mRH in such cases.

Radiation Therapy for Very Elderly Patients Aged 80 Years and Older With Squamous Cell Carcinoma of the Uterine Cervix.

OBJECTIVES: We carried out a retrospective review to determine the role played by radiation therapy in the treatment of very elderly patients with uterine cervical cancer. MATERIALS AND METHODS: Thirty elderly patients aged 80 years and older with squamous cell carcinoma of the uterine cervix, at clinical stages IB-IVA, underwent radiation therapy. Of these 30 patients, 6 received external irradiation alone and 24 received external irradiation and intracavitary brachytherapy. A total median dose of 69.0 Gy (range, 45.6 to 75.4 Gy) was delivered to the cervical tumors. No patients underwent chemotherapy. RESULTS: At a median follow-up time of 24 months, 7 patients had developed recurrences, including local recurrences in 3 and distant metastases in 5. The local control and distant metastasis-free rates were 88% and 79%, respectively, at 2 years. The disease-free, cause-specific, and overall survival rates were 69%, 77%, and 75%, respectively, at 2 years. Primary tumor size, T category, and clinical stage were found to be significant prognostic factors for distant metastasis. Age and primary tumor size were considered as being significant variables that affected survival. With the exception of a transient hematologic reaction, there were no therapy-related toxicities of grade ≥3. CONCLUSIONS: Radiation therapy was safe and effective regarding local control of uterine cervical cancer in elderly patients aged 80 years and older, and appeared to contribute to their prolonged survival. Curative radiation therapy should be considered as a viable treatment option, even in very elderly patients.

Radiation therapy for stage IVA uterine cervical cancer: treatment outcomes including prognostic factors and risk of vesicovaginal and rectovaginal fistulas.

PURPOSE: To evaluate the safety and efficacy of radiation therapy for stage IVA uterine cervical cancer and to identify an optimal radiation regimen. RESULTS: Seventeen of the 28 patients developed recurrence after radiation therapy (local recurrence in 10 and distant metastasis in 12). The local control and distant metastasis-free rates at 3 years in all patients were 61% and 49%, respectively. Fourteen patients died after radiation therapy, and all but 2 died of tumor progression. The disease-free, cause-specific, and overall survival rates at 3 years in all patients were 32%, 49%, and 45%, respectively, and the estimated median survival time was 32 months. Tumor size (P = 0.007) and involvement in the lower third of vagina (P = 0.006) were significant prognostic factors for local control. Older age (P = 0.018) and performance status (P = 0.020) were significant prognostic factors for distant metastasis. The presence of hydronephrosis was the sole significant prognostic factor for survival (P = 0.026). Only 2 patients developed grade 3 late toxicities (vesicovaginal fistula and radiation proctitis, respectively). MATERIALS AND METHODS: Twenty-eight patients with stage IVA uterine cervical cancer received radiation therapy. All patients initially received external pelvic irradiation at a median dose of 50.4 Gy in 28 fractions. Twenty patients also received high-dose-rate intracavitary brachytherapy at a median dose of 22 Gy in 4 fractions. These fraction sizes were lower than conventional sizes. The total median dose for all 28 patients was 68.7 Gy. CONCLUSIONS: Radiation therapy is safe and effective for treatment of stage IVA uterine cervical cancer. The reduced radiation dose per fraction may contribute to the prevention of vesicovaginal fistula formation.

Comparison of plasma amino acid profile-based index and CA125 in the diagnosis of epithelial ovarian cancers and borderline malignant tumors.

BACKGROUND: We previously developed a new plasma amino acid profile-based index (API) to detect ovarian, cervical, and endometrial cancers. Here, we compared API to serum cancer antigen 125 (CA125) for distinguishing epithelial ovarian malignant tumors from benign growths. METHODS: API and CA125 were measured preoperatively in patients with ovarian tumors, which were later classified into 59 epithelial ovarian cancers, 21 epithelial borderline malignant tumors, and 97 benign tumors including 40 endometriotic cysts. The diagnostic accuracy and cutoff points of API were evaluated using receiver operating characteristic (ROC) curves. RESULTS: The area under the ROC curves showed the equivalent performance of API and CA125 to discriminate between malignant/borderline malignant and benign tumors (both 0.77), and API was superior to CA125 for discrimination between malignant/borderline malignant lesions and endometriotic cysts (API, 0.75 vs. CA125, 0.59; p < 0.05). At the API cutoff level of 6.0, API and CA125 had equal positive rates of detecting cancers and borderline malignancies (API, 0.71 vs. CA125, 0.74; p = 0.84) or cancers alone (API, 0.73 vs. CA125, 0.85; p = 0.12). However, API had a significantly lower detection rate of benign endometriotic cysts (0.35; 95 % CI, 0.21-0.52) compared with that of CA125 (0.65; 95 % CI, 0.48-0.79) (p < 0.05). CONCLUSIONS: API is an effective new tumor marker to detect ovarian cancers and borderline malignancies with a low false-positive rate for endometriosis. A large-scale prospective clinical study using the cutoff value of API determined in this study is warranted to validate API for practical clinical use.

Radiation Therapy for Para-Aortic Lymph Node Metastasis from Uterine Cervical Cancer.

AIM: To evaluate the efficacy of radiation therapy for para-aortic lymph node metastases from uterine cervical cancer and to identify an optimal radiation regimen. PATIENTS AND METHODS: A total of 80 metastatic para-aortic lymph nodes, ranging from 11-50 mm (median=20 mm) on computed tomography, in 22 patients with squamous cell carcinoma of the uterine cervix were initially treated with radiation therapy. Total radiation doses for para-aortic lymph node metastases were 40-61.2 Gy (median=50.4 Gy) in 1.8-2 Gy fractions. RESULTS: Eight out of the 22 patients remained alive at a median follow-up of 32 months. Seven irradiated lymph nodes, 20-50 mm in diameter, in four patients progressed after irradiation at total doses of 44-50.4 Gy. No metastatic lymph nodes administered >50.4 Gy (median=55.8 Gy) exhibited progression after irradiation. All metastatic lymph nodes ≤ 25 mm in diameter irradiated with 50 or 50.4 Gy were controlled. The 3-year lymph node progression-free rates were 78% in the cohort of 22 patients and 89% considering all 80 metastatic lymph nodes. Apart from transient hematological reactions, two patients developed grade 3 or more therapy-related toxicities, including radiation proctitis in one and hemorrhagic cystitis and colitis in another. CONCLUSION: Radiation therapy can effectively control para-aortic lymph node metastases in patients with uterine cervical cancer. A total dose of 50.4 Gy in 1.8 Gy fractions is sufficient to control metastatic lymph nodes ≤ 25 mm in diameter, whereas a higher dose (approximately 55.8 Gy) may be required for larger nodes.

Attitudes toward cervical cancer screening among women receiving human papillomavirus vaccination in a university-hospital-based community: interim 2-year follow-up results.

AIM: This study investigated the status of cervical cancer screening among women in a university hospital-based community who received catch-up human papillomavirus (HPV) vaccinations as a basic element of our community-based cervical cancer prevention advocacy. METHODS: Self-administered questionnaires were distributed to 173 women working or studying in the community at their first HPV vaccination in 2010, at the third vaccination, and 2 years later. Their demographics and attitudes toward the Pap test were analyzed. RESULTS: The median age of the participants was 27.5 years and 88.2% were sexually active. Before the first vaccination, 38.5% (57/148) of the screening targets had never had a Pap test. Among the women who completed the third vaccination, Pap test experiences within the recent 2 years increased from 45.3% (63/139) at the first vaccination to 71.2% (99/137) at the third vaccination, and 67.5% (54/80) 2 years later. In 45.3% of the screening targets who had never had a Pap test at the time of their first HPV vaccination, their first Pap test was followed by their vaccination. CONCLUSIONS: Having biennial Pap tests in accordance with the Japanese national cancer screening guideline was shown to be difficult even for the women in the medical community; however, education about the Pap test and the efficacy of HPV vaccination in providing opportunistic screening encouraged them to have their first or suspended Pap test. Our interim data suggest the need for urgently changing the cervical cancer prevention strategy for young adult women who are excluded from the national HPV vaccine program.

Amino acid profile index for early detection of endometrial cancer: verification as a novel diagnostic marker.

BACKGROUND: Plasma amino acid profiles (PAAPs) vary in individual cancer patients, and it has been suggested that they may be useful for early detection of several types of cancer. We evaluated the diagnostic performance of a profile index for endometrial cancer composed of multiple plasma amino acids as a novel biomarker and compared its diagnostic performance with that of CA125. METHODS: Plasma amino acid levels of 80 patients with endometrial cancer, 122 with benign gynecological diseases, and 240 age- and body mass index-matched control subjects were measured using liquid chromatography and mass spectrometry. After univariate analysis, we applied a multiplex model based on the PAAP multivariate analysis to distinguish patients with endometrial cancer from control subjects. We compared the diagnostic performance of the multiple PAAP index (API) with that of CA125. RESULTS: The levels of several plasma amino acids were significantly different in patients with endometrial cancer. The area under the receiver operating characteristic curves (AUC) used to distinguish endometrial cancer patients from control subjects was 0.94. The AUC for API was significantly larger than that for CA125 (P = 0.0068). For the same specificity of 98.3 %, API showed a significantly higher sensitivity (60.0 %, 95 % CI, 43.3-75.1) than that of CA125 (22.5 %, 95 % CI, 10.1-38.5). In stage I cases, API showed significantly higher positivity than that of CA125 (P = 0.0002). CONCLUSIONS: The sensitivity and disease specificity of API for early-stage detection of endometrial cancer was superior to CA125. This novel plasma biomarker has the potential to become a diagnostic and screening marker for endometrial cancer.

Radiation therapy for pelvic lymph node metastasis from uterine cervical cancer.

OBJECTIVES: This study aimed to evaluate the efficacy of radiation therapy for pelvic lymph node metastasis from uterine cervical cancer and identify an optimal radiation regimen. METHODS: A total of 111 metastatic pelvic lymph nodes, ranging from 11 to 56 mm (median, 25 mm) on CT/MRI, in 62 patients with uterine cervical cancer were treated initially with curative radiation therapy, with 46 patients receiving concurrent chemotherapy. Total radiation doses ranged from 45 to 61.2 Gy (median, 50.4 Gy) in 1.8-2 Gy (median, 1.8 Gy) fractions. RESULTS: At a median follow-up of 33 months, 46 of the 62 patients survived. Only 2 irradiated lymph nodes, 24 and 28 mm in diameter, in 1 patient progressed after irradiation alone with 50.4 Gy in 1.8 Gy fractions. All 33 metastatic lymph nodes ≥ 30 mm in diameter were controlled by irradiation at a median dose of 55.8 Gy. The 3-year lymph node-progression free rates were 98.2% in all 62 patients and 98.0% in all 111 metastatic lymph nodes. Except for transient hematologic reactions, 2 patients developed grade ≥ 3 therapy-related toxicities, 1 with an ulcer and the other with perforation of the sigmoid colon. In addition, 2 patients experienced ileus after irradiation. CONCLUSIONS: Radiation therapy effectively controlled pelvic lymph node metastases in patients with uterine cervical cancer, with most nodes <24 mm in diameter controlled by total doses of 50.4 Gy in 1.8 Gy fractions and larger nodes controlled by 55.8 Gy, particularly with concurrent chemotherapy. Higher doses to metastatic lymph nodes may increase intestinal toxicities.

The role of radiation therapy for uterine cervical cancer with distant metastasis.

OBJECTIVE: We carried out a review to determine the role of radiation therapy in uterine cervical cancer with distant metastasis. METHODS: Forty-four patients with uterine cervical cancer with distant metastasis underwent radiation therapy; 29 of these also underwent chemotherapy. A total dose of 19.8-90.4 Gy (median 62.9 Gy) was delivered to the cervical tumors. RESULTS: Thirty-three patients died during the follow-up period of 1-94 months (median 10 months) after irradiation. The overall survival rate at 3 years was 20%, and the estimated median survival time was 15 months. Ten patients developed primary tumor progression, and the primary tumor control rate at 3 years was 49%. A distant metastatic site and primary tumor size were significant prognostic factors for their survival. Total radiation dose was considered a significant and useful variable for primary tumor control. With the exception of transient hematologic reactions and hemorrhagic cystitis, there were no therapy-related toxicities of grade 3 or greater. CONCLUSIONS: Radiation therapy was safe and effective for local control in patients with uterine cervical cancer with distant metastasis. More aggressive treatment, including radiation therapy with a curative radiation dose, should be considered for patients with favorable prognostic factors for survival.

Analysis of stage IVB endometrial carcinoma patients with distant metastasis: a review of prognoses in 55 patients.

BACKGROUND: Adequate treatment for extremely advanced endometrial cancer is unknown. The purpose of this study was to clarify the prognosis of patients with stage IVB endometrial carcinoma and the validity of treatment. Furthermore, we evaluated whether there was a connection between the prognosis and the site of metastasis. METHODS: The prognoses of 55 patients with stage IVB endometrial carcinoma were studied with reference to the initial treatment method and the metastatic site at the time of the initial treatment. RESULTS: The median survivals of the group of 35 patients who were initially treated with surgery and the group of 10 patients who underwent radiotherapy or chemotherapy as their initial treatment followed by surgery were 11.5 months and 9.5 months, respectively. The residual tumor diameter after surgery was precisely measured in 40 of these 45 patients. The prognosis was significantly better in the patients with a residual tumor diameter of less than 2 cm compared to those with a tumor diameter of 2 cm or greater, and the median survival periods in these two groups were 23.5 months and 11.5 months, respectively (P = 0.027). Furthermore, the prognosis of patients with lung metastasis was significantly better than that of patients with non-lung hematogenous metastasis; the median survival periods of these two groups were 18.5 months and 10.5 months, respectively (P = 0.014). CONCLUSION: For operable patients, surgery as an initial treatment and reduction of the residual tumor size to less than 2 cm appeared to contribute to a better prognosis. In addition, conservative initial treatment and the presence of non-lung hematogenous metastasis were poor prognostic factors.

Historical control study of paclitaxel-carboplatin (TJ) versus conventional platinum-based chemotherapy (CAP) for epithelial ovarian cancer.

BACKGROUND: As the first-line chemotherapy for epithelial ovarian cancer, the paclitaxel-carboplatin (TJ) regimen has replaced the cyclophosphamide, epirubicin, and cisplatin or carboplatin (CAP) regimen in our institutes since 1998. Both regimens were retrospectively compared for effectiveness and safety to verify the adequacy of the TJ regimen. METHODS: Women with epithelial ovarian cancer at FIGO stage Ic-IV were enrolled into the study and were assigned to either the CAP group (57 cases, from 1991 until 1998) or the TJ group (49 cases, from 1998 until 2002). The response rate, progression-free survival (PFS), and overall survival (OS) were compared in both groups. Adverse effects were also evaluated. RESULTS: The TJ group received an average of 6.3 courses of paclitaxel at 170.6 mg/m2 and carboplatin with an AUC of 4.3, while the CAP group received 5.8 courses of cisplatin at 61.4 mg/m2. The response rates were 82.8% in the TJ group and 70.6% in the CAP group at stage III-IV. The median OS was 43.9 months in the TJ group and 44.3 months in the CAP group. There was no statistically significant difference in effectiveness between the two groups. Peripheral neuropathy, myalgia/arthralgia, and allergic reactions were found significantly more often in the TJ group, but every adverse effect occurring in the TJ group was clinically controllable. In contrast, renal dysfunction occurred more frequently in the CAP group. CONCLUSION: This study demonstrated that the TJ regimen is as effective as the CAP regimen in its antitumor effect for epithelial ovarian cancer, and has controllable adverse effects.