Fumiaki Takahashi

Outcomes of abdominal radical trachelectomy: results of a multicenter prospective cohort study in a Tohoku Gynecologic Cancer Unit

BackgroundThis study aimed to evaluate surgical, pregnancy, and prognostic outcomes of radical abdominal trachelectomy (RAT) for Japanese patients with early-stage cervical cancer.MethodsThis was a multicenter prospective cohort study conducted in member facilities of Tohoku Gynecologic Cancer Unit. Patients with FIGO 1A–1B1 squamous cell carcinoma were included.ResultsA total of 42 patients were registered in this study, and all patients underwent planned RAT. The median stromal invasion and median horizontal spread of resected specimens were 4.6 (range 1.0–10.0) and 12.4xa0mm (range 3.0–28.0), respectively. The median surgical time and median blood loss were 304xa0min (range 233–611) and 848xa0mL (range 250–3984), respectively. Five patients (11.9xa0%) received blood transfusion. Five of 18 (27.8xa0%) patients who attempted to conceive achieved pregnancy, and 3 patients had healthy babies. However, all pregnancies required assisted reproductive technology with in-vitro fertilization and embryo transfer. Four patients (9.5xa0%) received postoperative adjuvant therapy, and 3 patients (7.1xa0%) developed disease recurrence.ConclusionsRAT may be safely performed for Japanese patients with FIGO 1A–1B1 squamous cell carcinoma of the cervix, even in educational medical facilities. However, less-invasive surgery should be considered more often to improve pregnancy outcomes.

Clinical statistics of gynecologic cancers in Japan

Cervical, endometrial, and ovarian cancers, have both high morbidity and mortality among the gynecologic malignant tumors in Japan. The present study was conducted using both the population-based cancer registry and the gynecologic cancer registry to elucidate the characteristics of gynecologic malignant tumors in Japan. Based on nationwide estimates from the population-based cancer registry in Japan, the morbidities and mortality of cervical, endometrial, and ovarian cancers were obtained and used for analysis. Clinicopathologic factors for cervical cancer, endometrial cancer, ovarian cancer, including age, clinical stage, postsurgical stage, histological type, therapeutic strategy, and prognosis were retrieved from the gynecologic cancer registry published by the Japan Society of Obstetrics and Gynecology and used for analysis. The morbidities of cervical, endometrial, and ovarian cancers were 10,908, 13,606, and 9,384 women in 2012, respectively. The prevalence of endometrial cancer has significantly and consistently been increasing and represents the most common gynecologic malignant tumor in Japan. The mortalities of cervical, endometrial, and ovarian cancers were 2.1, 1.3, and 3.2 per 100,000 in 2012, respectively. In 2014, 52.2% of cervical cancer patients were classified as stage I, 22.5% as stage II, 10.2% as stage III, and 11.2% as stage IV. In addition, 71.9% of endometrial cancer patients were classified as stage I, 6.0% as stage II, 13.3% as stage III, and 7.5% as stage IV. Finally, 43.2% of ovarian cancer patients were classified as stage I, 9.1% as stage II, 27.6% as stage III, and 7.2% as stage IV. Twelve-point six percent of ovarian cancer patients received neoadjuvant chemotherapy.

Chronic pulmonary aspergillosis as a sequel to lobectomy for lung cancer

OBJECTIVESnChronic pulmonary aspergillosis (CPA) is an emerging complication after lobectomy for lung cancer. This retrospective study aimed to determine the incidence, main risk factors and clinical features of postoperative CPA in lung cancer patients.nnnMETHODSnThis study included lung cancer patients treated by lobectomy and with no previous history of thoracic surgery or coexistent aspergillosis at the time of surgery. The cumulative incidence of CPA was determined using death as a competing risk. Furthermore, the identified lung cancer patients were divided into CPA and non-CPA groups to compare their preoperative clinical features and to identify the risk factors of postoperative CPA by univariable and multivariable analyses. We also analysed the clinical features of CPA patients after diagnosis.nnnRESULTSnWe included 475 lung cancer patients. Of these, 17 patients (3.6%) developed CPA after the lobectomy. The cumulative postoperative incidence rate of CPA was 2.3% [95% confidence interval (CI), 0.8-3.8%] at 5 years and 7.9% (95% CI, 3.0-13.0%) at 10 years. There were significantly more men (P = 0.007), smokers (P = 0.002) and comorbid chronic obstructive pulmonary disease (COPD) (P = 0.008) and interstitial lung disease (ILD) (P = 0.009) patients in the CPA group than in the non-CPA group. Multivariable analysis identified comorbid COPD (P = 0.0019) and ILD (P = 0.0003) as significant risk factors. An antifungal treatment response was obtained in 6 patients (35%). The 1-year survival rate was 47% (follow-up periods, interquartile range: 3-78 months), and 5 of the total of 11 deaths were due to CPA.nnnCONCLUSIONSnThrough the present retrospective study, CPA seems to be a common sequel to lobectomy in lung cancer patients, and COPD and ILD represent strong risk factors of postoperative CPA. Because of the poor clinical outcome of lung cancer patients who develop CPA after lobectomy, careful follow-up using several examinations and chest radiographs to make CPA diagnosis may be essential.

Longitudinal changes of ocular blood flow using laser speckle flowgraphy during normal pregnancy

Purpose Innovative laser speckle flowgraphy (LSFG) enables noninvasive evaluation of retinal microcirculation and the usefulness has been reported in the field of ophthalmology. LSFG has allowed us to measure the real time changes of retinal blood flow without pupillary dilatations and contrast media. Herein, we investigated the change of retinal blood flow in normal pregnant women during gestation using LSFG. Methods A prospective cohort study was conducted in 53 pregnant women who visited our institution between January, 2013 and July, 2014. Finally, a total of 41 participants without any obstetric complications were available for evaluation. Retinal blood flow was measured with LSFG in a total of 4 times during pregnancy (T1. 11–13 weeks, T2. 19–21 weeks, T3. 28–30 weeks, T4. 34–36 weeks) and mean blur rate (MBR), blowout score (BOS), flow acceleration index (FAI), and resistive index (RI) are analyzed from these measurements. Relations between LSFG parameters and mean arterial blood pressure (MAP) are determined throughout pregnancy. Results MBR showed no significant changes throughout pregnancy. BOS showed a tendency to increase in the 3rd trimester. FAI values showed a slight increase from the 1st to 2nd trimester while a significant decrease was noted in the 3rd trimester. RI exhibited no changes between the 1st and 2nd trimesters, values decreased significantly after the 3rd trimester. MAP was positively correlated with BOS, and negatively correlated with FAI and RI. Conclusion The present study clearly demonstrated that profiles of LSFG parameters demonstrated a decrease of resistance in retinal blood vessels. These changes in indices provide a highly sensitive reflection of physiological changes in vascular resistance due to pregnancy. Thus, LSFG may be useful, as a non-invasive, diagnostic tool to detect pregnancy related disorders such as preeclampsia.

Early impact of the Japanese immunization program implemented before the HPV vaccination crisis

1 Department of Obstetrics and Gynecology, Showa University School of Medicine, Shinagawa-ku, Tokyo 142-8666, Japan 2 Department of Obstetrics and Gynecology, Tohoku University Graduate School of Medicine, Sendai, Japan 3 Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, Japan 4 Gynecologic Oncology, Hyogo Cancer Center, Akashi, Japan 5 Department of Gynecology, Cancer Institute Hospital, Tokyo, Japan 6 Gynecology Service, National Kyushu Cancer Center, Fukuoka, Japan 7 Department of Obstetrics and Gynecology, Kurume University School of Medicine, Kurume, Japan 8 Department of Clinical Research Network, Clinical Research, Innovation and Education Center, Tohoku University Hospital, Sendai, Japan 9 Department of Obstetrics and Gynecology, Kinki University, Osaka, Japan 10 Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan

Effects of chemotherapy on patients with recurrent cervical cancer previously treated with concurrent chemoradiotherapy: a retrospective multicenter survey in Japan

BackgroundPredictive factors of the efficacy of chemotherapy for Japanese patients with recurrent cervical cancer who have been previously treated with concurrent chemoradiotherapy (CCRT) are currently unknown, and hence we aimed to investigate this.MethodsWe retrospectively studied the prognostic outcomes of patients with recurrent cervical cancer treated with CCRT between 2002 and 2010 at four medical facilities.ResultsA total of 64 patients were included in this study. Forty-two patients received definitive CCRT and 22 patients received postoperative adjuvant CCRT, with 55 receiving platinum-based combination chemotherapy and nine receiving single-agent chemotherapy. The overall response rate (ORR) was 12.5xa0%, with one complete response. The median survival period was 12xa0months. The ORR and overall survival rate did not differ significantly according to recurrence site, post-CCRT interval, or chemotherapy regimen.ConclusionNone of the factors analyzed in this study were identified as positive predictive factors for the efficacy of chemotherapy in patients with recurrent cervical cancer after CCRT. Based on the results of previous studies, in order to improve long-term prognosis in recurrent cases, adjuvant chemotherapy should be considered as a potential treatment option for selected patients, especially as postoperative adjuvant therapy.

Assessing the effect of guideline introduction on clinical practice and outcome in patients with endometrial cancer in Japan: a project of the Japan Society of Gynecologic Oncology (JSGO) guideline evaluation committee

Objective The Japan Society of Gynecologic Oncology (JSGO) published the first practice guideline for endometrial cancer in 2006. The JSGO guideline evaluation committee assessed the effect of this guideline introduction on clinical practice and patient outcome using data provided by the Japan Society of Obstetrics and Gynecology (JSOG) cancer registration system. Methods Data of patients with endometrial cancer registered between 2000 and 2012 were analyzed, and epidemiological and clinical trends were assessed. The influence of guideline introduction on survival was determined by analyzing data of patients registered between 2004 and 2009 using competing risk model. Results In total, 65,241 cases of endometrial cancer were registered. Total number of patients registered each year increased about 3 times in the analyzed period, and the proportion of older patients with type II endometrial cancer rapidly increased. The frequency of lymphadenectomy had decreased not only among the low-recurrence risk group but also among the intermediate- or high-recurrence risk group. Adjuvant therapy was integrated into chemotherapy (p<0.001). Overall survival did not significantly differ before and after the guideline introduction (hazard ratio [HR]=0.891; p=0.160). Additional analyses revealed patients receiving adjuvant chemotherapy showed better prognosis than those receiving adjuvant radiation therapy when limited to stage I or II (HR= 0.598; p=0.003). Conclusion It was suggested that guideline introduction influenced the management of endometrial cancer at several aspects. Better organized information and continuous evaluation are necessary to understand the causal relationship between the guideline and patient outcome.

Incidence of Domestic Violence Against Pregnant Females After the Great East Japan Earthquake in Miyagi Prefecture: The Japan Environment and Children’s Study

OBJECTIVEnThis study aimed to clarify the correlation between the 2011 Great East Japan Earthquake and domestic violence (DV) against pregnant females after the disaster in Miyagi Prefecture, an area damaged by the earthquake and tsunami.nnnMETHODSnWe analyzed 7600 pregnant females from June to December 2011. The incidence of physical and mental DV and the proportions in the inland, north coastal, and south coastal areas of Miyagi Prefecture and nationwide were calculated, and a chi-square test was conducted for comparison. The risk factors for DV were estimated with multivariate logistic regression analyses on a prefecture-wide basis.nnnRESULTSnThe incidence levels for physical DV were found to be 5.9% in the north coastal area, which was significantly higher than in the inland area (1.3%, P=0.0007) and nationwide (1.5%, P<0.0001). There were no significant differences in the incidence of mental DV between the 3 areas in Miyagi Prefecture (inland 15.2%, north coast 15.7%, and south coast 18.8%) or nationwide (13.8%). Experiencing disease or injury in someone close and changes in the family structure were significantly associated with mental DV in Miyagi Prefecture.nnnCONCLUSIONnContinuous monitoring and support for pregnant females may be necessary to address this issue in disaster-affected areas. (Disaster Med Public Health Preparedness. 2017;11:216-226).

Clinicopathologic features and BRCA mutations in primary fallopian tube cancer in Japanese women

ObjectivenThe present study aimed to clarify the clinicopathological features, including the level of p53 protein expression and BRCA mutations, of primary fallopian tube cancer (PFTC) in Japanese women.nnnMethodsnA multicenter clinical survey was conducted at three Japanese institutions. Clinical data in patients with PFTC between 1998 and 2016 were collected. Immunohistochemical staining of p53 and BRCA mutation analysis by exome sequence using paraffin-embedded surgical resected specimens were performed.nnnResultsnA total of 40 patients with PFTC were enrolled in the study. The median age was 58 years (range: 38-78 years); 31 patients were menopausal. Thirty-four (85.0%) patients were diagnosed with serous adenocarcinoma (high grade, 33; low grade, 1). PFTC was classified into ampulla type, fimbriae type and undeterminable type by tumor-occupying lesion; ampulla type and fimbriae type occurred with the same frequency. Among 30 patients with high-grade serous adenocarcinoma, 6 patients showed germline mutations of BRCA1 (stop-gain 4 and frameshift deletion 2) and 2 patients showed germline mutation of BRCA2 (stop-gain 1 and frameshift deletion 1). However, only 1 patient had familial history of breast or ovarian cancer. Patients with BRCA mutations in the germline were frequently observed in ampulla type and FIGO stage I/II cancers, but no significant difference in the frequency of p53 overexpression and overall survival was observed.nnnConclusionsnAmong Japanese patients with PFTC, 26.7% presented with BRCA mutations in the germline. Additionally, p53 was important for the carcinogenesis in fallopian tubes, independent of the specific BRCA mutation.

Current Status of Uterine Leiomyosarcoma in the Tohoku Region: Results of the Tohoku Translational Center Development Network Survey

BackgroundTo prepare for a future clinical trial for improving the long-term prognosis of patients with uterine leiomyosarcoma (ULMS), we conducted a multi-institutional survey in the Tohoku region of Japan.MethodsWe conducted a retrospective cohort study between 2011 and 2014 in member institutions of the Tohoku Translational Research Center Development Network.ResultsA total of 53 patients with ULMS were registered in 31 institutions for the present survey. The median patient age was 56xa0years, 67.9% of the patients were postmenopausal, 88.7% had a performance status of 0 or 1, and only 6 patients (11.3%) showed preoperative evidence of malignancy. Although retroperitoneal lymphadenectomy was performed in only 26.4% of patients, 64.2% patients were identified as having FIGO stage 1 disease; 73.6% were eligible to undergo complete surgery. Among 36 patients who were treated with postoperative chemotherapy, 28 (77.8%) received docetaxel and gemcitabine combination therapy. The most frequent recurrence site was the lungs, and the median progression-free survival of all enrolled patients was 11.7xa0months. However, the median progression-free survival and the median overall survival in patients with stages III and IV disease were 3.4 and 11.4xa0months, respectively.ConclusionAlthough ULMS was associated with a high rate of complete or optimal surgery, the long-term prognosis was poor. Effective postoperative therapy should be developed to improve the long-term prognosis of patients with ULMS.