Resolution of large pelvic lymphocele after incidental intracystic hemorrhage caused by percutaneous catheter drainage: Case report.

We report the case of a large pelvic lymphocele after an ovarian cancer operation, which incidentally vanished after bleeding resulting from percutaneous catheter drainage. The patient was a 74-year-old woman with stage IVB ovarian cancer who underwent surgery including pelvic lymph node dissection. Three months after surgery, computed tomography revealed a large (13-cm diameter) pelvic lymphocele with associated bilateral hydronephrosis and left femoral vein thrombosis. The lymphocele was repeatedly drained by percutaneous aspiration, and the day after the second procedure, the drainage fluid became bloody. The catheter was clamped for 3 days and then removed. The lymphocele volume gradually decreased, and it was not seen on a computed tomography scan 70 days after drainage. The lymphocele did not recur prior to her death. In this case, the intracystic hemorrhage was considered to have served as a blood patch for lymph leakage.

Human papillomavirus vaccine effectiveness by age at first vaccination among Japanese women.

In Japan, the National Immunization Program against human papillomavirus (HPV) targets girls aged 12-16 years, and catch-up vaccination is recommended for young women up to age 26 years. Because HPV infection rates increase soon after sexual debut, we evaluated HPV vaccine effectiveness by age at first vaccination. Along with vaccination history, HPV genotyping results from 5795 women younger than 40 years diagnosed with cervical intraepithelial neoplasia grade 2-3 (CIN2-3), adenocarcinoma in situ (AIS), or invasive cervical cancer were analyzed. The attribution of vaccine-targeted types HPV16 or HPV18 to CIN2-3/AIS was 47.0% for unvaccinated women (n = 4297), but 0.0%, 13.0%, 35.7%, and 39.6% for women vaccinated at ages 12-15 years (n = 36), 16-18 years (n = 23), 19-22 years (n = 14), and older than 22 years (n = 91), respectively, indicating the greater effectiveness of HPV vaccination among those initiating vaccination at age 18 years or younger (P < .001). This finding was supported by age at first sexual intercourse; among women with CIN2-3/AIS, only 9.2% were sexually active by age 14 years, but the percentage quickly increased to 47.2% by age 16 and 77.1% by age 18. Additionally, the HPV16/18 prevalence in CIN2-3/AIS was 0.0%, 12.5%, and 40.0% for women vaccinated before (n = 16), within 3 years (n = 8), and more than 3 years after (n = 15) first intercourse, respectively (P = .004). In conclusion, our data appear to support routine HPV vaccination for girls aged 12-14 years and catch-up vaccination for adolescents aged 18 years and younger in Japan.

Prognosis of bulky pTIIB cervical cancer treated by radical hysterectomy comparing adenocarcinoma with squamous cell carcinoma using propensity score matching.

OBJECTIVE: To investigate whether radical hysterectomy (RAH) can effectively treat true Stage IIB (pTIIB) cervical adenocarcinoma (AC) because FIGO (clinical) Stage IIB cervical cancer is rarely treated with RAH and radiotherapy has unfavorable effects on AC. METHODS: We retrospectively analyzed data for 82 patients with Stage pTIIB cervical cancer who underwent RAH at our institution between January 1997 and December 2017. The end points were disease-free survival (DFS) and overall survival (OS) among squamous cell carcinoma (SCC) (n = 60) and AC (n = 22) patients. Kaplan-Meier survival analysis with and without propensity score matching was conducted to identify the impact of RAH. RESULTS: Para-aortic lymph node metastasis and tumor diameter were significant factors for recurrence, and adjuvant chemotherapy prevented recurrence on multivariate analysis. After propensity score matching, there was no significant difference in DFS and OS between the groups. Five-year DFS and OS of the SCC group were 0.505 (95% confidence interval [CI] 0.268-0.702) and 0.619 (95% CI 0.351-0.803), respectively, and those of the AC group were 0.444 (95% CI 0.232-0.638) and 0.602 (95% CI 0.351-0.782), respectively. CONCLUSION: Bulky Stage pTIIB cervical cancer is hard to cure, but RAH plus adjuvant therapy might be an option for radio-resistant pTIIB cervical AC.

Real prevalence of neural tube defects in Japan: How many of such pregnancies have been terminated?

The vital role of folic acid is to reduce the risk of having a neonate afflicted with neural tube defects. The prevalence of neural tube defects (myelomeningocele and anencephaly) has been reported in an incomplete form over the last 40 years in Japan. We aimed to evaluate the total number of neural tube defects including those delivered or terminated, to clarify the proportion of those terminated, and to internationally compare their prevalence. Through information on >311 000 deliveries obtained from 262 hospitals/clinics for 2 years of 2014 and 2015, we identified that the rate of total neural tube defects (termination of pregnancy, live births and stillbirths) was 8.29 per 10 000 deliveries for the year 2014 and was 8.72 for 2015, which were 1.5 and 1.6 times higher than the respective values (live births and stillbirths) reported. It is also observed that the ratio of the total number of myelomeningocele (termination of pregnancy, live births, and stillbirths) to that of anencephaly was approximately 1:1.2, that a half of pregnancies afflicted with neural tube defects were terminated, and that the proportion of termination of pregnancy due to myelomeningocele and due to anencephaly was 20% and 80%, respectively. Internationally, the real prevalence of neural tube defects in Japan was comparatively high, ranking fifth among the seven developed countries. In conclusion, the real prevalence of total neural tube defects was approximately 1.5 times higher than that currently reported by the Japan Association of Obstetricians and Gynecologists.

A study of treatments and outcomes in elderly women with cervical cancer.

OBJECTIVE: With the population aging, development of safe and effective treatments for elderly patients with cancer is needed. Although old age is considered a poor prognostic factor, this is not only because of the patient's disease condition or response to treatment, but also because of treatment strategy and intensity. The purpose of this study was to clarify the influence of age on treatment and prognosis in patients with cervical cancer. METHODS: Women with stage Ib-IV cervical cancer treated at our institution between 1997 and 2014 were retrospectively analyzed. Patients were stratified by age into groups for analysis, <65 years and ≥65 years. Categorical variables were compared using chi-squared and Fisher's exact tests. Survival analyses were performed using the Kaplan-Meier method, and comparisons were made using the log-rank test. Subsequently, Cox proportional hazards models were developed to find independent prognostic factors. RESULTS: Of 959 patients included in our study, 247 were ≥65 and 712 were <65 years of age. Elderly patients tended to be at a more advanced stage than younger patients (p < 0.001). Elderly patients more commonly had comorbidities. More received standard treatment in the younger patient group at any disease stage than in the elderly patient group (p < 0.001). Similar rates of adverse effects caused by surgery or radiotherapy were seen in patients from both groups. Although overall survival was statistically shorter in elderly patients (74.7 vs. 57.1%, p < 0.001), there was no significant difference in disease-specific survival for patients treated only with standard treatment. In multivariate analyses, clinical stage, histological type, treatment intensity, and primary surgery remained independent prognostic factors. Age was not an independent prognostic factor. CONCLUSIONS: The influence of age on prognosis in patients with cervical cancer was less than we expected. Elderly patients might have better outcomes depending on the type of standard treatment they receive. The appropriate modality and intensity of treatment should be based on the patient's general condition and background.

Renal function and urological complications after radical hysterectomy with postoperative radiotherapy and platinum-based chemotherapy for cervical cancer.

BACKGROUND: We aimed to clarify renal functional changes long term and serious urological complications in women with cervical cancer who undergo radical hysterectomy followed by pelvic radiotherapy and/or platinum-based chemotherapy to treat the initial disease. METHODS: Data on 380 women who underwent radical hysterectomy at the National Kyushu Cancer Center from January 1997 to December 2013 were reviewed. Main outcome measures were the estimated glomerular filtration rate (eGFR) and monitored abnormal urological findings. RESULTS: Postoperative eGFR was significantly lower than preoperative eGFR in 179 women with surgery alone and in 201 women with additional pelvic radiotherapy and/or chemotherapy (both P < 0.01). Two types of univariate analyses for eGFR reduction in women after treatment showed that older age, advanced stage, pelvic radiotherapy, and platinum-based chemotherapy were significant variables on both analyses. Two types of multivariate analyses showed that platinum-based chemotherapy or pelvic radiotherapy were associated with impaired renal function (odds ratio 1.96, 95% confidence interval 1.08-3.54 and odds ratio 2.85, 95% confidence interval 1.12-7.24, for the respective analyses). There was a higher rate of bladder wall thickening in women with pelvic radiotherapy had than those without it (17.4% vs. 2.7%, P < 0.01). One serious urological complication (intraperitoneal rupture of the bladder) occurred among women who underwent pelvic radiotherapy (0.6% vs. 0%). CONCLUSIONS: Surgeons should be aware that eGFR is reduced after platinum-based chemotherapy and/or postoperative pelvic radiotherapy. Serious and life-threatening urological complications are rare, but surgeons should be aware of the possibility during the long follow-up.

Improvement in the prognosis of ovarian cancer in the era before addition of molecular targeting therapy.

OBJECTIVE: The prognosis of ovarian cancer has improved because of platinum- and taxane-containing chemotherapy. We investigated the 5-year disease-specific overall survival and prognostic factors of patients with advanced ovarian cancer to elucidate the change in clinical course of ovarian cancer with the advance of chemotherapy for patients who developed relapse in the era before the addition of molecular targeting therapy. METHODS: We reviewed the clinical course of 134 patients with advanced ovarian cancer (FIGO Stage III and IV) treated in the past 11 years (1999-2010). We classified the patients into two groups: those who had been diagnosed with ovarian cancer from 1999 to 2005 (Group A) and those who had been diagnosed from 2006 to 2010 (Group B). We compared the 5-year disease-specific overall survival and median survival rates between these two groups. We also investigated the prognostic factors of 104 patients who developed relapse. RESULTS: The 5-year disease-specific overall survival rate was significantly higher in Group B than A (67.0% vs. 38.6%; P = 0.032). Chemotherapy containing pegylated liposomal doxorubicin hydrochloride, non-clear cell adenocarcinoma and intestinal resection were independent prognostic factors. CONCLUSIONS: The induction of new chemotherapeutic drugs and the increased variation of second- or third-line chemotherapy affected the improvement in overall survival of patients with advanced epithelial ovarian cancer.

Early Identification of Asymptomatic Pulmonary Embolism Proximal to the Subsegmental Arteries After Gynecologic Surgery.

Few studies have assessed whether cases of asymptomatic pulmonary embolism (PE) in the early postoperative phase are subsegmental versus more proximal. In this study, we investigated whether asymptomatic PE occurring just after gynecologic surgery was subsegmental, and we examined the background characteristics of patients who experienced PE within 2 months postoperatively. All hospital records were reviewed, yielding a total of 2052 women who had undergone surgeries performed by the gynecologic oncology team between 2003 and 2013 in the National Kyushu Cancer Center. Asymptomatic and symptomatic postoperative PE cases diagnosed by multidetector computed tomography angiography or lung scan were identified; after excluding 2 cases of preoperative PE, there were 15 (0.73%) cases of postoperative PE among 2050 women. Of the 15 cases, 9 (60%) were diagnosed on postoperative day 1 or 2. Of the 9 women, 4 had no or minor symptoms/signs other than decreased oxygen saturation as measured by pulse oximetry (Spo 2), and PE was segmental or more proximal in 3 cases. Only 1 of the 9 cases showed dyspnea. The remaining 4 cases showed dizziness or perspiration, suggesting PE. Univariate analysis showed age, operation time, hypertension, and preoperative d-dimer elevation to be associated with postoperative PE. Multivariate analysis demonstrated that a high (≥ 1 µg/mL) preoperative d-dimer level was associated with postoperative PE (odds ratio, 6.331; 95% confidence interval, 1.567-25.589). Most asymptomatic PE cases occurring within 2 days postoperatively were segmental or more proximal. Identification of early, asymptomatic postoperative PE may be clinically significant because most of these emboli are proximal to the subsegmental arteries.

[Nogitecan Hydrochloride Treatment for Patients with Recurrent Ovarian Cancer].

Nogitecan hydrochloride(topotecan)has shown efficacy in patients with recurrent ovarian cancer, but has not been used widely in Japan. We evaluated the efficacy and adverse effects of topotecan in 12 patients (median age, 62 years) treated for recurrent ovarian cancer between 2000 and 2013. Four patients had relapsed after primary treatment, and 8 had relapsed at least twice. Seven patients had been treated with more than 3 prior regimens. Initial treatment of the 12 patients consisted of intravenous topotecan (1.0-1.4 mg/m2/day) for 5 consecutive days. Initial doses were based on previous chemotherapy and/ or renal function, with reduced doses administered to patients with severe adverse effects during prior courses of treatment. The 12 patients received a total of 54 courses of topotecan(range, 1-15 courses). Of these 12 patients, one achieved a partial response and 6 had stable disease. The median time to progression was 14.4 weeks. All 12 patients had grade 3-4 myelosuppression, while none had febrile neutropenia or severe non-hematologic toxicities. Patients who received higher doses or increased courses of chemotherapy had apparently more severe adverse events. These findings suggested that topotecan should be used as a second- or third-line treatment, rather than later, in patients with tumor recurrence, with its dose reduced according to the physical status of each patient. Such strategies may enhance both the efficacy and safety of topotecan in patients with recurrent ovarian cancer.

Immune thrombocytopenia associated with solid cancer.

We describe a case of immune thrombocytopenia (ITP) associated with ovarian cancer. At the patient's first visit to hospital, high platelet-associated IgG and low platelet count (74 × 10(9)/L) were noted on blood test. She was diagnosed as having ITP complicated by ovarian cancer. Four days after surgery, the platelet count had increased to within the normal range. This is the first report of a patient with ITP complicated by ovarian cancer in which the platelet count reverted to normal soon after surgery for the ovarian cancer. We also investigated the characteristics of similar solid cancers with ITP at National Kyushu Cancer Center, Fukuoka, Japan.

Prediction of histological types of endometrial cancer by endometrial cytology.

AIM: Few studies have examined the accuracy of preoperative endometrial cytology in diagnosing low- and high-risk histology in women with endometrial cancer (EC). This single-institutional retrospective study compared the accuracy of endometrial cytology and biopsy in preoperatively predicting low-risk and high-risk histology of EC. METHODS: Between January 2006 and March 2013, 198 women with EC were examined by endometrial cytology, endometrial biopsy and hysterectomy specimen in National Kyushu Cancer Center. Among these women, 110 had endometrial cytology samples available to compare with endometrial biopsy, and were enrolled in our study (mean age ± standard deviation: 59.57 ± 10.32 years). Single-use plastic endometrial suction curettes were used in 12 of the 110 cases and thin metallic curettes for the rest. RESULTS: For type 2 EC, which includes grade 3 endometrioid adenocarcinoma and non-endometrioid histology, biopsy was 67.6% sensitive (25/37) and 84.9% specific (62/73); whereas cytology was 70.3% sensitive (26/37) and 91.8% specific (67/73). Cytology precisely diagnosed only one of 14 cases of serous carcinoma, but it diagnosed 11 of the 14 cases as type 2 EC, and its accuracy in distinguishing EC types was not inferior to endometrial biopsy (10/14). For EC, 9.1% (10/110) were unevaluable using biopsy, significantly more than the 0% (0/110) by cytology (P = 0.002). CONCLUSION: Although preoperative prediction of serous carcinoma was difficult, endometrial cytology had a higher evaluable rate for EC types. Endometrial cytology may complement endometrial biopsy in preoperative women with EC.

Secondary leukemia after chemotherapy and/or radiotherapy for gynecologic neoplasia.

OBJECTIVE: Secondary leukemia is a known complication of chemotherapy and radiotherapy. It was generally recognized that leukemia secondary to chemotherapy was due to the use of alkylating agents in the treatment of ovarian cancer. Recently, many types of chemotherapeutic agents have been used in the treatment of gynecologic malignancies in addition to ovarian cancer. We analyzed the clinical characteristics and outcome of patients with recent onset of secondary leukemia after the treatment of gynecologic cancer to consider the diagnosis and management of secondary leukemia. MATERIALS AND METHODS: We reviewed the clinical charts and follow-up data of patients with gynecologic malignancies treated in the past 20 years. During this period, 2482 newly diagnosed invasive gynecologic cancers were treated in our institution. All patients with secondary leukemia were analyzed for clinical background, latency period (interval between the diagnosis of primary carcinoma and the development of leukemia), treatment, and outcome. We also reviewed the literature for secondary leukemia under gynecology using the PubMed. RESULTS: Four patients were found to have developed secondary leukemia after the treatment of gynecologic malignancies during this period. The cumulative risk of secondary leukemia was approximately 0.38%. All patients received platinum-based chemotherapy. Two patients received combination chemotherapy and/or bone marrow transplantation, and 1 of these 2 patients lived more than 6 years but died of recurrent ovarian cancer. CONCLUSIONS: Long survival time might be expected in patients who show complete response to bone marrow transplantation and/or combination chemotherapy for secondary leukemia. In recent years, we have aggressively used various types of anticancer drugs for the treatment of not only ovarian cancer but also uterine cervical cancer and endometrial cancer. Physicians need to keep in mind the risk of secondary leukemia in the follow-up of long-term survivors after several courses of chemotherapy and radiotherapy.

Prognostic significance of the treatment-free interval in patients with recurrent endometrial cancer.

OBJECTIVE: To identify prognostic factors of recurrent endometrial cancer, and clarify whether the treatment-free interval (TFI) predicts outcome in a wide spectrum of patients. STUDY DESIGN: The clinical data of 60 patients treated for recurrent stage I-IV endometrial cancer between 1997 and 2012 were reviewed retrospectively. The Kaplan-Meier method and Cox regression analysis were used to estimate overall survival (OS) following recurrence and determine the factors influencing outcomes. RESULTS: The median age at initial treatment was 59 (range 38-80) years and the median post-recurrence overall survival time was 40.0 (range 1.8-156.7) months. Multivariate analysis showed lymph node metastasis (hazard ratio (HR) 2.80; 95% confidence interval (95%CI) 1.29-6.09; p=0.009), TFI (HR 0.33; 95% CI 0.15-0.76; p=0.008), and symptomatic recurrence (HR 2.31, 95% CI 1.11-4.83, p=0.0025) were independent prognostic factors. Patients whose tumors recurred after a TFI≥12 months had better response rates than did those with a TFI<12 months (p<0.001). CONCLUSION: TFI is a significant prognostic factor in recurrent endometrial cancer. Furthermore, the effect of chemotherapy on recurrent endometrial cancer is probably influenced by the duration of TFI.

The safety and efficacy of cisplatin plus gemcitabine in recurrent ovarian cancer.

BACKGROUND: The activity and synergy for the combination treatment of cisplatin and gemcitabine has been identified in a variety of human tumor cells, including ovarian cancer cells, and has been widely approved for the treatment of non-small cell lung cancer, pancreatic cancer and biliary tract cancer. As the gastrointestinal symptoms with cisplatin therapy are commonly considered to negatively affect the quality of life of patients more than those experienced with carboplatin therapy, carboplatin is generally preferred over cisplatin in combination therapy. This study evaluated the safety and efficacy of cisplatin plus gemcitabine in patients with recurrent ovarian cancer. METHODS: Patients with recurrent ovarian, peritoneal or fallopian tube cancer, who had failed with multiple other chemotherapy agents, including platinum, received cisplatin (30 mg/m(2)) plus gemcitabine (750 mg/m(2)) on days 1 and 8 of every 28 days for between 1 and 4 cycles. RESULTS: In total, 18 patients were treated with cisplatin and gemcitabine between 2006 and 2011. There were 1 complete and 5 partial responses, producing an overall response rate of 33.4 %. Median overall survival was 11.0 months. Grade 4 neutropenia and thrombocytopenia were seen in 11.1 and 22.2 % of patients, respectively. Non-hematological toxicity was less than Grade 1. CONCLUSIONS: Non-hematological toxicity with combined cisplatin and gemcitabine therapy was considered tolerable and did not impede patient quality of life. However, this drug combination should be monitored for hematologic toxicity.

[A case of metastatic choriocarcinoma responding to combination chemotherapy with paclitaxel and carboplatin].

A 53-year-old woman with choriocarcinoma (high-risk gestational trophoblastic disease: FIGO score 17) was treated with paclitaxel (175 mg/m(2)) and carboplatin (AUC=5). The patient was treated with an EMA/CO regimen as initial chemotherapy, but she developed EMA/CO-induced interstitial lung disease after the 3rd course of treatment. After high-dose steroid therapy, she received combination chemotherapy with paclitaxel and carboplatin. Her hCG-/b dropped to <0.1 ng/mL after 11 courses of the chemotherapy. A paclitaxel+carboplatin regimen is potentially effective for high-risk GTD, but a more effective combination or schedule with a platinum-taxane regimen should be explored.

[Neoadjuvant chemotherapy with intraperitoneal paclitaxel for advanced gynecologic cancer].

OBJECTIVES: We evaluated safety and activity of intraperitoneal paclitaxel [=PTX (ip)] for neoadjuvant chemotherapy (NAC) of patients with advanced gynecologic cancer. METHODS: 13 patients with gynecologic cancer who had diffuse peritoneal dissemination received PTX (ip) with systemic chemotherapy (TC regimen) for NAC. After 3-6 courses of NAC, interval debulking surgery (IDS) was done. At IDS, we explored intraperitoneal cavity and debulked as much as possible, and examined pathological effects of NAC. RESULTS: PTX (ip) was well tolerated with apparent anti-cancer activity. Eleven patients were done with IDS after 3-6 NAC courses. Ten of 11 patients were completed an optimal surgery without extended resections. Eight of 11 patients with IDS had grade 2 (5 cases) or grade 3 (3 cases) effects of pathological examination. CONCLUSION: According to this exploratory research, we considered PTX (ip)=80 mg/m2 with PTX (iv)=115 mg/m2 and CBDCA (iv) AUC=4 as an optimum drug dose. Although evaluated in a small number of patients, PTX (ip) appeared to have safety and anti-cancer activity, and should be evaluated further.