Shigeru Honma

Reactivity of two monoclonal antibodies (Troma 1 and CAM 5.2) on human tissue sections: analysis of their usefulness as a histological trophoblast marker in normal pregnancy and trophoblastic disease

In normal and molar pregnancy, a morphological discrimination between nonvillous trophoblasts which lie scattered in the placental bed and surrounding maternal cells is considered to be difficult. We examined the reactivity of two monoclonal antibodies (Troma 1 and CAM 5.2) against cytokeratin by an immunoperoxidase technique and analyzed their usefulness as a histological trophoblast marker. Materials were taken from 42 uteri with normal pregnancy, 7 uteri with hydatidiform mole, 2 uteri with gestational choriocarcinoma, 1 fallopian tube with nongestational choriocarcinoma, 5 delivered term placentae of normal pregnancy, and 5 nongestational uteri. The reactivities of Troma 1 on frozen sections and those of CAM 5.2 on paraffin sections were identical. They reacted with surface epithelium and gland epithelium in the nongestational uterine corpus. In the implantation site of normal and molar pregnancy, they reacted with villous and nonvillous trophoblasts as well as endometrial gland epithelium. In gestational and nongestational choriocarcinoma, they reacted with carcinoma cells specifically. Since the histological detection of gland epithelium may not be difficult, it was concluded that the two antibodies were very beneficial as a histological marker for trophoblasts in normal pregnancy and trophoblastic disease.

Interleukin 6-producing malignant mesothelioma

SummarySystemic amyloidosis of the amyloid A (AA) type, is occasionally associated with various neoplasms, but the cause is still unclear. We obtained interleukin 6 (IL-6)-producing cells designated YO from a primary culture of a malignant peritoneal mesothelioma of epithelial type obtained from a 62-year-old woman. Post mortem examination revealed that the patient had systemic amyloidosis of the AA type. The supernatant media of YO cells, as well as recombinant human IL-6, successfully induced nonneoplastic liver cells to produce serum AA (SAA). Our data suggest that IL-6 produced by the tumor cells may have played an important role in the paraneoplastic syndrome of AA amyloidosis in this patient.

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.

Origin of adenocarcinoma cells observed on cervical cytology

OBJECTIVE To clarify the ratio of diseases suspected when malignant glandular cells are observed on cervical cytology. STUDY DESIGN Seventy cases of cervical adenocarcinoma/adenosquamous carcinoma, 207 cases of endometrial adenocarcinoma, 7 cases of tubal adenocarcinoma and 83 cases of ovarian adenocarcinoma were reviewed. The positive rate in cervical cytology performed 3 months before surgery was calculated. Based on the positive rate for each entity and the number of cases treated in the previous 10 years, we estimated the incidence of disease responsible for malignant glandular cells on cytology. RESULTS The positive rate was 93% in cervical adenocarcinoma/adenosquamous carcinoma, 45% in endometrial adenocarcinoma, 14% in tubal adenocarcinoma and 6% in ovarian adenocarcinoma. These positive rates and case numbers at our institute indicated the percentage of suspicious diseases to be 38% for cervical aaenocarcinoma/adenosquamous carcinoma, 53% for endometrial adenocarcinoma, 1% for tubal adenocarcinoma and 8% for ovarian adenocarcinoma. CONCLUSION When a cytologic specimen suggested the existence of adenocarcinoma, the most probable disease was endometrial adenocarcinoma, and the second was cervical adenocarcinoma/adenosquamous carcinoma. Adnexal malignancies were responsible in 9% of cases. In the case of positive cervical cytology suggesting adenocarcinoma, the ratio of suspicious diseases is as valuable as the cytologic findings for the differential diagnosis.

Establishment and characterization of a subline predisposed to pulmonary metastasis from a human gestational choriocarcinoma cell line in nude mice

A subline predisposed to pulmonary metastasis was successfully derived by repeating in vivo selection of GCH‐1, a human gestational choriocarcinoma cell line, in nude mice. While the parent line GCH‐1, transplanted subcutaneously to nude mice, induced pulmonary metastasis in a few of the host animals, the newly established subline GCH‐l(m) successfully metastasized to the lungs in 100% of them. Compared with GCH‐1, GCH‐l(m) exhibited a higher degree of cell atypia, a lower capacity for cell growth and markedly higher productivity for human chorionic gonadotropin (hCG). Another characteristic of this subline was its enhanced growth after the addition of a pulmonary extract obtained from nude mice. The relationship of these findings to the mechanisms of metastasis of this cancer was discussed.

Two cases of endometrial cancer arising from adenomyosis during aromatase inhibitors therapy after mastectomy

Among gynaecological neoplasms, both adenomyosis and endometrial cancer are encountered relatively often. However, endometrial cancer arising from adenomyosis is considered rare (Kumar and Anderson 1958; Colman and Rosenthal 1959; Koike et al. 2013). We, herein, report our experience with two cases of this disease in patients taking oral aromatase inhibitors (AIs) after mastectomy. Although this disease has occasionally been reported, there have been few reports suggesting the risk factors for occurrence of this condition or effective treatment, whereas our present report focuses on this issue.

Disappearance of a metastatic brain tumor and achievement of long-term survival with a good quality of life after a combination of systemic chemotherapy with the P-glycoprotein inhibitor nifedipine in a patient with ovarian cancer

Dear Editor, Systemic chemotherapy has not been established for metastatic brain tumors from primary ovarian cancer. Here, we report our experience with an important case in which the efficacy of systemic chemotherapy was enhanced and prolonged survival with a good quality of life (QOL) was achieved by using nifedipine to inhibit P-glycoprotein. The patient was a 53-year-old woman. In July 1998, she underwent an optimal surgery for stage IIIc ovarian cancer (serous adenocarcinoma). In August 2006, the disease recurred as metastasis in the para-aortic lymph nodes. Although these lesions disappeared after chemotherapy with paclitaxel plus carboplatin (CBDCA), four metastatic brain tumors were observed in July 2007: a lesion in the cerebellar vermis; an asymptomatic nodular lesion in the left basal ganglion; and an asymptomatic nodular lesion in the right and left cerebellar hemisphere, each. These lesions disappeared after Gamma Knife radiosurgery. In June 2008, yet another asymptomatic metastatic lesion was found in the cortex of the apical portion of the right temporal lobe, which disappeared after Gamma Knife radiosurgery. However, in March 2011, another asymptomatic metastatic lesion (8×5 mm) was observed in the medial portion of the sensory region of the right parietal lobe (Fig. 1a). We opted to administer systemic chemotherapy, anticipating that it would not only have therapeutic effects on brain metastases but also exert a preventive effect against both metastasis to other organs and recurrence. Pegylated liposomal doxorubicin (PLD) plus CBDCA, which has been shown to be effective for recurrent ovarian cancer, was selected. However, because of the previously reported poor outcomes for brain metastasis from primary ovarian cancer [3], we decided to combine PLD plus CBDCA with nifedipine in the hope of increasing the anti-cancer drug efficacy. The patient provided informed consent and was prescribed a sustained-release nifedipine tablet (20 mg) to be taken every morning and evening for 7 days, starting on day 1 of each cycle of chemotherapy. After two cycles, contrast-enhanced magnetic resonance imaging (MRI) showed a 75 % reduction in lesion size (Fig. 1b). After four cycles, the lesion was no longer visible on contrast-enhanced computed tomography (CT) (Fig. 1c). After five cycles, its disappearance was confirmed by contrast-enhanced MRI (Fig. 1d). The serum cancer antigen 125 level, which was 162.7 U/ml initially, normalized to 19.3 U/ml after three cycles. There were no variations in blood pressure during nifedipine treatment and no adverse events such as palpi tations, nausea, or facial f lushing. The chemotherapy-related adverse events were minor. Treatment was completed after seven cycles in November 2011. As of this writing, the patient is completely independent in her activities of daily living, with a performance status of 0. She has a good QOL and is under outpatient management. * Toru Yanase toyanase@gmail.com

Multivariate analysis of prognostic factors in stage I ovarian cancer

AbstractBackground. As the prognosis of ovarian cancer has improved with recent therapy, some prognostic factors have lost their clinical significance. The purpose of this study was to evaluate prognostic factors in stage I ovarian cancer in patients with improved prognosis because of cisplatin combination chemotherapy. Methods. Multivariate analysis was performed with 14 clinicopathologic prognostic factors obtained from 170 patients with stage I ovarian cancer (borderline tumors were excluded), who had been surgically treated between 1983 and 1995. Results. The 5-year survival rate was 94.5% for all stage I patients, 98.0% in stage IA, 100% in stage IB, and 92.6% in stage IC. Significant prognostic factors determined by the Kaplan-Meier method were spontaneous rupture of the capsule and capsular invasion (P < 0.05, and P < 0.01). Multivariate analysis, however, showed that spontaneous rupture of the capsule was the only significant prognostic factor (P = 0.02627). Both analyses showed that histologic type, histologic grading, intrapelvic cytology, operative procedure, and chemotherapy had little influence on prognosis. Conclusion. Multivariate analysis showed that spontaneous rupture of the capsule was the only significant prognostic factor in patients with stage I ovarian cancer who received cisplatin chemotherapy.