Positron emission tomography with (18)F-fluorodeoxyglucose of uterine sarcoma: a comparison with magnetic resonance imaging and power Doppler imaging

OBJECTIVE: The effectiveness of positron emission tomography with (18)F-fluorodeoxyglucose (FDG-PET) for diagnosis of uterine sarcoma was evaluated in comparison to the effectiveness of magnetic resonance (MR) imaging and power Doppler imaging. METHOD: The cases of five Osaka City University Hospital patients diagnosed with uterine sarcoma based on histopathological examination, in whom FDG-PET, MR imaging, and power Doppler imaging studies had been performed preoperatively, were reviewed. A comparative study of the usefulness of these three imaging modalities for diagnosis of sarcoma was conducted. Tumors comprised three leiomyosarcomas, one endometrial stromal sarcoma, and one carcinosarcoma. RESULTS: FDG-PET examinations were 100% positive for the five sarcomas; MR imagings were 80% positive (four of five cases), and US was 40% positive (two of five cases). The mean standardized uptake value of the sarcomas was 4.5 +/- 1.3. CONCLUSION: The sarcoma lesions were clearly imaged by FDG-PET. FDG-PET may be a most useful diagnostic method for uterine sarcoma.     

Mutational analysis of BRCA1 and BRCA2 and clinicopathologic analysis of ovarian cancer in 82 ovarian cancer families: two common founder mutations of BRCA1 in Japanese population.

We analyzed genetic alterations in BRCA1 and BRCA2 genes among 82 ovarian cancer families in Japan. The clinical characteristics of BRCA-associated ovarian cancer patients were compared with cases carrying no mutations as well as with population controls. Using a direct sequencing method, 45 of the 82 ovarian cancer families were found to carry BRCA1 or BRCA2 germ-line mutations (40 with BRCA1 and 5 with BRCA2). In 24 independent mutations of BRCA1, 5 recurrent mutations were found and 2 of them, the L63X and Q934X mutations, were detected in seven and eight independent families, respectively. In addition, 16 mutations of BRCA1 and 3 mutations of BRCA2 have never been described previously. In consideration of clinicopathological features, there was a significantly higher proportion of tumors with serous adenocarcinoma and of cases of advanced stages in the BRCA1 or BRCA2 cases than in those of the controls. On the other hand, there were no differences of mean age at diagnosis between patients with BRCA1 or BRCA2 mutation and those of the controls. Our results indicate that the features of BRCA-associated ovarian cancer in Japan appear to be similar to those in Western countries, and the L63X and Q934X mutations of BRCA1 appear to be common founder mutations unique to the Japanese population.     

Autocrine/paracrine regulation of human endometrial stromal remodeling by laminin and type IV collagen

The biological roles of laminin and type IV collagen in human endometrial stromal tissues were investigated by the evaluation of the expression levels in human endometrial tissues using immunohistochemistry. In addition, normal human endometrial stromal cells were cultured in vitro on laminin- or type IV collagen-coated plates and subjected to cytological analyses. Cyclic production of laminin and type IV collagen were detected and the two productions were significantly increased in late proliferative and late secretory endometrial stromal cells. Unstimulated endometrial stromal cells proliferated with specific growth structures that varied depending on the extracellular matrix component coated on the culture plates. The expression levels of integrin subunits on endometrial stromal cells were sufficiently enhanced by 8Br-cAMP treatment to mask any differences in the growth structures induced by the extracellular matrix components. 8Br-cAMP-stimulating stromal cells exhibited significant survival on laminin-coated plates, while 8Br-cAMP-deprived stromal cells, after 8Br-cAMP stimulation, showed significant survival on type IV collagen-coated plates. In conclusion, human endometrial stromal cells produce laminin and type IV collagen, and these productions are possibly regulated by ovarian estrogen and progesterone. Human endometrial stromal cells specifically bind to laminin and type IV collagen via integrins, and regulate endometrial stromal cell structures, viability and differentiation. Thus, laminin and type IV collagen may autoregulate human endometrial stromal remodeling during the menstrual cycle in an autocrine and paracrine fashion.     

Effect of malignant ascitic fluids and OK-432 on the induction of LAK activity in peripheral blood mononuclear cells of gynecological cancer patients]

Recently, successful treatment of peritonitis carcinomatosa by intraperitoneal administration of lymphokine-activated killer (LAK) cells followed by intraperitoneal recombinant interleukin 2 (rIL-2) has been reported by several authors, in spite of the well documented results of the immunosuppressive activity of malignant ascitic fluid. We investigated the effect of malignant ascitic fluid on in vitro induction of LAK cells obtained from patients' peripheral blood mononuclear cells. We also examined whether Streptococcal preparation OK-432, which has been instilled into the peritoneal cavity to treat malignant ascites, is able to synergize with rIL-2 to induce LAK activity, and the following results were obtained; 1. A little augmentation of LAK activity was observed at a lower concentration of malignant ascitic fluid, while the results were diversified at a concentration higher than 10%. In two cases out of six, a severe suppressive effect was observed at a concentration higher than 40%. At the higher concentration, fewer cells were recovered after a 5 day culture in all cases. 2. No augmentation of LAK activity following the combination of OK-432 with rIL-2 was observed. At a lower concentration of OK-432 (ranging from 0.01-0.04KE/ml), the number of cells increased in comparison with rIL-2 alone. These results suggest that the potential of adoptively transferred LAK cells followed by rIL-2 was not effectively suppressed by malignant ascitic fluid in vivo and that the administration of OK-432 followed by rIL-2 could induce a larger number of various killer cells than rIL-2 alone.     

The effect of intraperitoneal administration of OK-432 with recombinant interleukin-2 to patients with peritonitis carcinomatosa of recurrent gynecological cancer and changes in ascitic lymphocyte subsets

The effect of intraperitoneal administration of OK-432 followed by intraperitoneal instillation of recombinant interleukin-2(rIL-2) was examined in tumor bearing animals and in four recurrent gynecological cancer patients with peritonitis carcinomatosa which had been resistant to chemotherapeutic drugs. Seven days after intraperitoneal inoculation of tumor cells (10(6) cells/body of MH134 hepatoma into C3H/He mice and 10(5) cells/body of Meth-A fibrosarcoma into BALB/C mice, respectively), OK-432 was administered intraperitoneally. Two days later, a 14 day course of daily intraperitoneal instillation of rIL-2 followed. The survival time for animals treated with OK-432 combined with rIL-2 was significantly prolonged. Three of the 8 C3H/He mice and one of the 8 BALB/C mice in this group survived more than 150 days without forming ascites. However, the group treated by rIL-2 alone did not survive for more than 40 days. The group treated by OK-432 alone as well as the untreated group did not survive for more than 20 days. Ascitic fluid disappeared clinically in two of four cases and decreased in the rest. Ascitic cancer cells disappeared in one case and decreased in three cases. The serum CA125 level declined significantly in all cases. The surface markers of ascitic lymphocytes were analyzed by flow cytometry on day 8. The CD4+ subset accounted for 70-90% whereas the CD8+ subset accounted for only 7-17%. In three cases in which two color analysis was performed, the CD4+, CD29+ helper inducer T cell was dominant. We could conclude that LAK cells were not the main effector cells.     

Postoperative adjuvant chemotherapy with cisplatin, etoposide, and pirarubicin for endometrial carcinoma patients with lymph node metastasis: A pilot study

We evaluated the effects of a combined chemotherapy regimen on endometrial carcinoma in 14 patients with lymph node metastasis. After surgery, the patients were treated with 3 cycles of chemotherapy (PVP regimen) every 4 weeks. The PVP regimen consisted of 75 mg/m2 cisplatin on day 1, 40 mg/m2 pirarubicin (P) on day 1, and 75 mg/m2 etoposide (VP-16: V) on days 2, 3 and 4. The effect of adjuvant chemotherapy was evaluated based on progression-free survival (PFS), overall survival (OS), and adverse effects. The 5-year PFS rate was 52% [95% confidence interval (CI), 10-94%], and the 5-year OS rate was 50% (95% CI, 16-84%). The major toxicity was myelosuppression. One hundred percent of patients had neutropenia above grade 3, but all recovered from myelosuppression. PVP therapy may be an effective adjuvant therapy for endometrial carcinoma patients with lymph node metastasis used as an alternative to radiation therapy.     

Irinotecan (CPT-11) and cisplatin as first-line chemotherapy for advanced ovarian cancer

OBJECTIVE: To evaluate the efficacy and toxicity of a combination of irinotecan (CPT-11) and cisplatin as first-line chemotherapy in advanced ovarian cancer. METHODS: Twenty-six patients with previously untreated advanced epithelial ovarian cancer were enrolled in this study. CPT-11 60 mg/m(2) was administered intravenously on days 1, 8, and 15 in combination with cisplatin 60 mg/m(2) on day 1. Cycles were repeated every 28 days for at least two cycles. The median patient age was 55 years (range, 37-75), and the median performance status was 1. RESULTS: Objective responses were recorded in 19 of 25 eligible patients (76%; 95% confidence interval, 55-91%). Complete responses were obtained in 2 patients (8%), and partial response in 17 patients (68%). Stable disease was recorded in 2 patients (8%) and progressive disease in 2 (8%). The median time to response was 62 days (range, 28-234 days). The median survival time for all 25 patients was 30.9+ months (range, 4.1-60.0+ months). The major toxic effects were leukopenia, neutropenia, and diarrhea. Grade 3 or 4 leukopenia, neutropenia, and diarrhea occurred in 17 (68%), 20 (83.3%), and 5 patients (20%), respectively. Thrombocytopenia was less common. No treatment-related deaths occurred. CONCLUSION: The combination of CPT-11 and cisplatin showed significant activity in chemotherapy-naive patients with advanced ovarian cancer. Neutropenia was the dose-limiting adverse effect, whereas diarrhea was mainly mild to moderate.     

Clinical evaluation of intermittent administration of CDDP in advanced ovarian cancer

We examined the effects of intermittent cisplatin therapy (ICDDPT) on advanced ovarian cancer patients (OCP). Most OCPs had received surgical removal of primary lesion, and histopathological analysis indicated epithelial tumors. Four OCPs were stage 3, three were stage 4 and one was stage 2 (n = 8). After surgical treatment and induction chemotherapy, ICDDPT with 20-25 mg/day CDDP was given for 3 or 5 days, every 3 months. During the intervals, maintenance immunochemotherapy with Tegafur and OK-432 was given. Following ICDDPT all patients are alive, the longest survival time being 3 years and 10 months. Three have survived at least 3 years, 1 for at least 2 years and 3 for at least 1 year. Adverse drug reaction (ADR) was analysed with reference to the total dose of CDDP, i.e. under 500 mg, over 500 mg-under 1,000 mg and over 1,000 mg. Abnormal laboratory findings in platelets (thrombocytopenia), Hb, BUN, Creatinine, GOT and GPT were observed at the all doses. These ADR were not increased with the increasing dose so that accumulative toxicity was not observed. Therefore ICDDPT was seen to be effective in treating OCP.