Hidekatsu Nakai

Cytopathologic and clinicopathologic features of ovarian hepatoid carcinoma. A case report.

BACKGROUND Hepatoid carcinoma is a rare ovarian tumor and is thought to be a different histopathologic subtype from hepatoid-type yolk sac tumor based upon its pathologic features. However, the cytopathologic characteristics of ovarian hepatoid carcinoma (OHC) have not been reported previously. We report the clinicopathologic and cytopathologic features and immunoreactivity of a case of OHC. CASE A 36-year-old woman presented to our department with lower abdominal pain. A left ovarian tumor was found on pelvic examination, magnetic resonance imaging and computed tomography. The tumor was diagnosed as a hepatoid carcinoma of the left ovary based upon the histopathology of the surgically resected specimen. Cytopathologic specimens from a tumor touch preparation of the tumor exhibited pleomorphic tumor cells with abundant cytoplasm. The nuclei contained rough, granular chromatin and large, prominent nucleoli. Several tumor cells were multinucleated. Tumor cells were immunoreactive for alpha-fetoprotein (AFP). Hematoxylin and eosin staining revealed that the tumor cells were in a sinusoidal pattern resembling hepatocellular carcinoma without any glandular formation. The tumor cells were negative for human chorionic gonadotropin while positive for AFP, alpha-1-antitripsin, CA-125 and carcinoembryonic antigen. CONCLUSION Cytopathologic examination is of considerable aid in the diagnosis of OHC since cytopathologic preparations highlight the characteristic cell pleomorphism.

Feasibility of concurrent cisplatin use during primary and adjuvant chemoradiation therapy: a phase I study in Japanese patients with cancer of the uterine cervix

BackgroundAlthough the prognostic advantages of concurrent cisplatin (CDDP) chemoradiation therapy (CCRT), for uterine cervical cancer (UCC) has been demonstrated, the feasibility of concurrent CDDP administration has not yet been evaluated. We determined the optimal CDDP dose for both weekly and monthly schedules during primary and adjuvant CCRT in patients with UCC.MethodsThe study was conducted as a phase I, dose-escalation trial. Concurrent CDDP was started at the dose of 30 mg/m2 for the weekly schedule and at 50 mg/m2 for the monthly schedule, and the doses were steadily escalated to the maximum tolerated dose (MTD).ResultsA total of 45 patients with UCC (25 receiving primary CCRT and 20 receiving adjuvant CCRT) were entered in the study. In both the primary and adjuvant CCRT patients, the MTD was observed to be 40 mg/m2 for the weekly schedule and 80 mg/m2 for the monthly schedule. Dose-limiting toxicity was observed in 10 patients (granulocytopenia in 9 patients and diarrhea in 1 patient). Disease recurrence was confirmed in 6 patients in the primary CCRT group during a mean follow-up period of 22.4 ± 13.2 months, and in patients 3 in the adjuvant CCRT group during a mean follow-up period of 17.7 ± 6.8 months.ConclusionFor Japanese patients with UCC receiving primary or adjuvant CCRT therapy, the recommended CDDP dose was determined to be 30 mg/m2 for the weekly schedule and 75 mg/m2 for the monthly schedule.

Evaluation of Parametrial Spread in Endometrial Carcinoma

OBJECTIVE: To evaluate the detailed clinicopathologic characteristics of parametrial spread in uterine endometrial cancer. METHODS: We retrospectively identified 334 individuals with uterine endometrial cancer who had undergone radical hysterectomy between 1988 and 2007. Parametrial spread was determined by histopathological analysis of surgically resected specimens. RESULTS: Twenty-eight (8.4%) individuals had histopathologically confirmed parametrial spread, and lymphatic or blood vessel invasion (22 cases) was the most frequently observed type of parametrial spread; direct invasion to parametrial connective tissue (five cases) or cardinal lymph node metastasis (four cases) were less frequently observed. Parametrial spread occurred not only in individuals with cervical involvement but also in individuals with more than half myometrial invasion, retroperitoneal (pelvic, paraaortic, or both), lymph node metastasis, ovarian metastasis, positive peritoneal cytology results, and lymphovascular space invasion. Twenty-six individuals (92.9%) with parametrial spread showed more than one of these histopathological factors (median number of factors 3, range 1–6); the other two individuals had lymphovascular space invasion alone. In 10 individuals with parametrial spread (35.7%), the condition recurred during the median follow-up period of 49 months, and initial recurrence was observed in the lung in six individuals (60.0%). Although the long-term prognosis for those with parametrial spread was significantly poorer than that of those without parametrial spread, both among all individuals (P<.001) and among individuals with International Federation of Gynecology and Obstetrics stage III (P<.05), multivariate analysis showed that parametrial spread was not an independent prognostic factor for uterine endometrial cancer. CONCLUSION: Parametrial spread cannot be predicted by cervical involvement alone but may be predicted by various lymphovascular space invasion-related histopathologic factors. Further, parametrial spread may not be an independent prognostic factor in individuals with uterine endometrial cancer. LEVEL OF EVIDENCE: III

Clinical tumor diameter and prognosis of patients with FIGO stage IB1 cervical cancer (JCOG0806-A)

OBJECTIVE In order to determine indications for less radical surgery such as modified radical hysterectomy, the risk of pathological parametrial involvement and prognosis of FIGO stage IB1 cervical cancer patients undergoing standard radical hysterectomy with pre-operatively assessed tumor diameter≤2 cm were investigated. METHODS We conducted a retrospective multi-institutional chart review of patients with FIGO stage IB1 cervical cancer who underwent primary surgical treatment between 1998 and 2002. The eligibility criteria for the analyses were (i) histologically-proven squamous cell carcinoma, adenocarcinoma or, adenosquamous cell carcinoma, (ii) radical hysterectomy performed, (iii) clinical tumor diameter data available by MR imaging or specimens by cone biopsy, and (iv) age between 20 and 70. Based on the clinical tumor diameter, patients were stratified into those with the following tumors: i) 2 cm or less (cT≤2 cm) and ii) greater than 2 cm (cT>2 cm). We expected 5-year OS of ≥95% and parametrial involvement<2-3% for patients with cT≤2 cm who underwent radical hysterectomy. RESULTS Of the 1269 patients enrolled, 604 were eligible for the planned analyses. Among these, 571 underwent radical hysterectomy (323 with cT≤2 cm and 248 with cT>2 cm). Parametrial involvement was present in 1.9% (6/323) with cT≤2 cm and 12.9% (32/248) with cT>2 cm. Five-year overall survivals were 95.8% (95% CI 92.9-97.6%) in cT≤2 cm and 91.9% (95% CI 87.6-94.8%) in cT>2 cm patients. CONCLUSION Patients with cT≤2 cm had lower risk of parametrial involvement and more favorable 5-year overall survival. They could therefore be good candidates for receiving less radical surgery.

Phase II study of single-agent gemcitabine in heavily pretreated Japanese patients with recurrent ovarian cancer.

BackgroundGemcitabine has been recommended as an active agent for salvage chemotherapy in patients with recurrent epithelial ovarian cancer, but no clinical study of this agent has been conducted for Japanese women with ovarian cancer. To evaluate the efficacy and feasibility of gemcitabine for heavily pretreated Japanese patients with recurrent epithelial ovarian cancer, we conducted a single-institute phase II clinical trial.MethodsAll patients had received a minimum of two previous chemotherapy regimens, In this study, gemcitabine was administered at 1000 mg/m2 on days 1, 8, and 15 of a 28-day cycle.ResultsA total of 28 patients participated in this study. Although 5 patients (17.9%) needed dose reduction to 800 mg/m2 because of thrombocytopenia and granulocytopenia, all patients completed an average of 6.7 courses (range, 2–24 courses). The overall response rate, including five partial responses, was 17.9% (95% confidence interval [C I], 6.0–36.9). The median time to progression was 8.8 months and the median survival period was 11.2 months. Grade 3/4 hematological toxicities included leucopenia, 35.7%; granulocytopenia, 39.3%; anemia, 46.4%; and thrombocytopenia, 10.7%. However, no grade 3/4 nonhematological toxicity was observed. The mean delay in treatment was 5.0 ± 7.7 days (range, 0–15 days) in a total of 562 cycles.ConclusionSingle-agent gemcitabine is an effective salvage chemotherapy regimen in heavily pretreated Japanese patients with recurrent epithelial ovarian cancer.

Platelet-derived endothelial cell growth factor predicts of progression and recurrence in primary epithelial ovarian cancer.

We investigated the clinical significance of platelet-derived endothelial cell growth factor (PD-ECGF) as measured by enzyme-linked immunosorbent assay in primary epithelial ovarian cancers (EOC), finding amounts to be significantly greater in cancers than in normal ovarian tissue (p<0.01). PD-ECGF was significantly more abundant in stages III and IV than in lower stages (p<0.05), and also was high in tumors with macroscopically evident metastases in the peritoneal cavity (p<0.05), or pelvic (p<0.01) or paraaortic (p<0.01) lymph node metastases. Further, PD-ECGF was significantly lower in mucinous than in serous adenocarcinomas (p<0.05). No significant correlation was seen between PD-ECGF and histologic grade, maximum intraperitoneal metastatic tumor diameter (<2 vs.>2 cm), or presence of demonstrable malignant cells in peritoneal fluid. In stage III disease, PD-ECGF exhibited significant correlation with recurrence (p<0.05). Our data suggested that results of PD-ECGF assays in primary tumors can predict progression and recurrence of EOC.

Comprehensive assessment of the expression of the SWI/SNF complex defines two distinct prognostic subtypes of ovarian clear cell carcinoma

Somatic mutations in the ARID1A tumor-suppressor gene have been frequently identified in ovarian clear cell carcinoma (CCC) cases. BAF250a encoded by ARID1A is a member of the SWI/SNF complex, but the expression and mutation status of other SWI/SNF subunits have not been explored. The current study aimed to elucidate the biological and clinical significance of the SWI/SNF complex subunits, by assessing the expression and mutation status of SWI/SNF subunits, and distinct genomic aberrations associated with their expression. Of 82 CCC specimens, 38 samples presented no BAF250a expression, and 50 samples exhibited the loss of at least one subunit of the SWI/SNF complex. Cases which lack at least one SWI/SNF complex component exhibited significantly more advanced stages, faster growth and stronger nuclear atypia compared with SWI/SNF-positive samples (p<0.05). Although BAF250a expression is not related to poor prognosis, the group presenting the loss of at least one SWI/SNF complex subunit exhibited significantly shorter overall and progression-free survivals (p<0.05). A multivariate analysis suggested that the expression status of the SWI/SNF complex serves as an independent prognostic factor (p<0.005). The cases positive for all SWI/SNF subunits demonstrated significantly greater DNA copy number alterations, such as amplification at chromosomes 8q.24.3 and 20q.13.2-20q.13.33 (including ZNF217) and deletion at chromosomes 13q12.11-13q14.3 (including RB1), 17p13.2-17p13.1 (including TP53) and 19p13.2-19p13.12. In conclusion, the CCCs exhibiting the loss of one or multiple SWI/SNF complex subunits demonstrated aggressive behaviors and poor prognosis, whereas the CCCs with positive expression for all SWI/SNF components presented more copy number alterations and a favorable prognosis.

Adenocarcinoma of the lower female genital tract in patients with Herlyn-Werner-Wunderlich syndrome.

We report 2 patients with Herlyn-Werner-Wunderlich syndrome, 1 with advanced endometrioid adenocarcinoma of the semiobstructed side of the uterine cervix and 1 with primary clear cell carcinoma of the obstructed side of the upper vagina.

Realistic fear of cervical cancer risk in Japan depending on birth year

ABSTRACT Objective: In Japan, the possible adverse events upon HPV vaccination was widely reported in the media. MHLW announced the suspension of aggressively encouraging HPV vaccination in 2013, and inoculation rate has sharply declined. The aim of the present study was estimation of future cervical cancer risk. Methods: The latest data on vaccination rate at each age in Sakai City were first investigated. The rate of experiencing sexual intercourse at the age of 12, 13, 14, 15, 16, 17 and throughout lifetime is assumed to be 0%, 1%, 2%, 5%, 15%, 25%, and 85% respectively. The cervical cancer risk was regarded to be proportional to the relative risk of HPV infection over the lifetime. The risk in those born in 1993 whom HPV vaccination was not available yet for was defined to be 1.0000. Results: The cumulative vaccination rates were 65.8% in those born in 1994, 72.7% in 1995, 72.8% in 1996, 75.7% in 1997, 75.0% in 1998, 66.8% in 1999, 4.1% in 2000, 1.5% in 2001, 0.1% in 2002, and 0.1% in 2003. The relative cervical cancer risk in those born in 1994–1999 was reduced to 0.56–0.70, however, the rate in those born in 2000–2003 was 0.98–1.0, almost the same risk as before introduction of the vaccine. Discussion: The cumulative initial vaccination rates were different by the year of birth. It is confirmed that the risk of future cervical cancer differs in accordance with the year of birth. For these females, cervical cancer screening should be recommended more strongly.

Reproductive Outcome of Infertile Patients with Fibroids Based on the Patient and Fibroid Characteristics; Optimal and Personalized Management.

Aims: To analyze the detailed clinical course of infertile patients with uterine fibroids and to identify optimal and personalized treatment based on the patient or fibroid characteristics. Methods: Retrospective analysis of a case series was performed on 176 infertile patients with fibroids. The patients were classified into different groups according to different treatments (conservative infertility treatment, myomectomy and non-myomectomy surgery). Patient or fibroid characteristics for different groups were analyzed for a possible correlation with the reproductive outcome. Results: The cumulative pregnancy rates by conservative treatment plateaued in 1 year. Myomectomy improved the reproductive outcome in patients who did not conceive with conservative infertility treatments. The most important determinant of the reproductive outcome in patients by conservative treatment prior to surgery was a past patient history of pregnancy. The most important determinant of the reproductive outcome after myomectomy was patient age. Conclusion: Myomectomy should be considered when infertile patients with fibroids do not conceive within 1 year of conservative infertility treatments. The most important determinant of reproductive outcome after myomectomy is patient age. Therefore, for patients younger than 40, the treatment schedule should be carefully considered so that the patients can sufficiently benefit from myomectomy and assisted reproductive technology.