Surgery for endometrial cancers with suspected cervical involvement: is radical hysterectomy needed (a GOTIC study)?

BACKGROUND: Radical hysterectomy is recommended for endometrial adenocarcinoma patients with suspected gross cervical involvement. However, the efficacy of operative procedure has not been confirmed. METHODS: The patients with endometrial adenocarcinoma who had suspected gross cervical involvement and underwent hysterectomy between 1995 and 2009 at seven institutions were retrospectively analysed (Gynecologic Oncology Trial and Investigation Consortium of North Kanto: GOTIC-005). Primary endpoint was overall survival, and secondary endpoints were progression-free survival and adverse effects. RESULTS: A total of 300 patients who underwent primary surgery were identified: 74 cases with radical hysterectomy (RH), 112 patients with modified radical hysterectomy (mRH), and 114 cases with simple hysterectomy (SH). Median age was 47 years, and median duration of follow-up was 47 months. There were no significant differences of age, performance status, body mass index, stage distribution, and adjuvant therapy among three groups. Multi-regression analysis revealed that age, grade, peritoneal cytology status, and lymph node involvement were identified as prognostic factors for OS; however, type of hysterectomy was not selected as independent prognostic factor for local recurrence-free survival, PFS, and OS. Additionally, patients treated with RH had longer operative time, higher rates of blood transfusion and severe urinary tract dysfunction. CONCLUSION: Type of hysterectomy was not identified as a prognostic factor in endometrial cancer patients with suspected gross cervical involvement. Perioperative and late adverse events were more frequent in patients treated with RH. The present study could not find any survival benefit from RH for endometrial cancer patients with suspected gross cervical involvement. Surgical treatment in these patients should be further evaluated in prospective clinical studies.

Selective cytotoxicity of adriamycin immunoconjugate of monoclonal antibody MSN-1 to endometrial adenocarcinoma in vitro and in vivo.

Missile therapy, which destroys cancer cells specifically, has been regarded as an effective treatment modality for carcinoma. The monoclonal antibody MSN-1 (IgM), which reacts strongly with endometrial adenocarcinomas, was combined with adriamycin (ADM) by a disulfide bond using N-succinimidyl-3-(2-pyridyldithio) propionate (SPDP) and 2-iminothiolane. Its selective cytotoxicity against SNG-II was examined in a colony formation in vitro, and on athymic mice in vivo. The results of our study suggest that the or IC50, of the MSN-1-ADM immunoconjugate against SNG-II to be 57 times that of ADM alone in vitro. The reductions in resected weights of target tumor cells, at the local site of the MSN-1-ADM immunoconjugate treatment, were 25% with caudal vein administration, and 38% with local administration, as compared with the untreated group, in vivo. There was no weight loss in treated mice. Our results suggest that this MSN-1-ADM immunoconjugate has potential clinical application in the treatment of endometrial adenocarcinomas.

Gestational choriocarcinoma whose responsible pregnancy was a complete hydatidiform mole identified by PCR analysis with new sequence tagged site primers.

We report a case where the pregnancy responsible for a gestational choriocarcinoma was not the antecedent pregnancy or the second normal term delivery, but a complete hydatidiform mole that had advanced to clinically invasive mole. This responsible pregnancy was identified by polymerase chain reaction analysis (PCR). PCR analysis was performed by using five new sets of sequence-tagged site (STS) primers on four chromosomes (chr. 1, D1S225; chr. 3, D3S1744; chr. 12, D12S1090; chr. 18, D18S849 and D18S877). The constitution of alleles of choriocarcinoma was shown to be almost identical with that of the husband on every marker. The allele patterns of choriocarcinoma on D3S1744 and D12S1090 were not observed with DNA from the patient. The band pattern originating from molar DNA was also identical with those of the husband and choriocarcinomas on D18S849 and D1S225.

Effect of gelonin immunoconjugate with monoclonal antibody MSN-1 to endometrial adenocarcinoma on antigen-producing tumor cells in vivo.

Missile therapy, which destroys cancer cells specifically, has been advocated as an effective modality for the treatment of carcinoma. We have developed an immunoconjugate consisting of the monoclonal antibody MSN-1 (IgM), which reacts strongly with endometrial adenocarcinomas, combined with a plant hemitoxin named gelonin via a disulfide bond using N-succinimidyl-3-(2-pyridyldithio) propionate and 2-iminothiolane, and examined its selective cytotoxicity in athymic mice. The reductions in resected weights of target tumor cells, at the local site of MSN-1-gelonin immunoconjugate treatment, were 96% with local administration and 75% with caudal vein administration, as compared with the untreated group. There was no weight loss in treated mice. Our results suggest that this MSN-1-gelonin immunoconjugate has potential clinical applications in the treatment of endometrial adenocarcinomas.

Survey of Cryptosporidium oocysts from adult cattle in a slaughter house.

Cryptosporidian oocysts were surveyed in rectal stools of adult cattle which were carried into slaughterhouse from April 1995 to July 1996. We morphologically and histologically investigated oocysts, and experimentally infected the isolated oocysts to mice and rats. Cryptosporidian oocysts were detected from 24 of 512 cattle (4.7%). They were spherical or ovoid, and the size was 7.0-7.9 x 5.3-6.1 microm. Mice and rats inoculated orally with 10(5)-10(7) oocysts became infected and discharged oocysts in the feces for a period of more than two months. Developing parasites were detected from the stomach of mice, and not detected from the other digestive tract. From these findings, present isolates from cattle were identified as Cryptosporidium muris.

Effects of gelonin immunoconjugate of monoclonal antibody MSN-1 to endometrial adenocarcinoma on antigen-producing tumor cells in vitro.

Missile therapy, which destroys cancer cells specifically, has been considered to be an effective modality for treatment of carcinoma. We have developed a monoclonal antibody MSN-1 (immunoglobulin class: IgM), of which the immunogen is the endometrial adenocarcinoma cell line SNG-II, which strongly reacts with endometrial adenocarcinomas. We describe an immunoconjugate consisting of the MSN-1 and a plant hemitoxin named gelonin which has revealed to assume selective cytotoxicity against the SNG-II in a colony formation assay in vitro. The results of our study suggest that the 'inhibitory concentration' or IC50, of the MSN-1-gelonin immunoconjugate against the SNG-II was 188 fold that of gelonin alone. These results indicated that the MSN-1-gelonin immunoconjugate exhibited highly selective cytotoxicity to endometrial adenocarcinoma, which expressed an epitope against the MSN-1, and it is suggested that the MSN-1-gelonin immunoconjugate has possibility of clinical application to treatment of endometrial adenocarcinomas.

[Characterization of anti human uterine endometrial cancer antibody (MSN-1) and its usefulness in clinical application].

We have produced a monoclonal antibody (MSN-1), by using our endometrial cancer-cultured cell line (SNG-II) as an immunogen. MSN-1 belongs to the IgM immunoglobulin class and mainly recognized the Lewis carbohydrate moiety. It seldom, reacted immunohistochemically with normal endometrium but with about 90% of endometrial cancer cases. So, we evaluated the effectiveness of its use in clinical application. We studied the relationship between the stage of cancer and reactivity to MSN-1, and that between the reactivity of moderately differentiated endometrial cancer to MSN-1 and a 5-year survival rate. Endometrial cancer with a poor prognosis tended to react poorly to MSN-1, suggesting the possibility that the reactivity to MSN-1 is useful as a new prognostic factor. A study of endometrial hyperplasia revealed that the reactivity to MSN-1 was high in the high risk group (individuals diagnosed as endometrial cancer later). This suggested that the analysis of the expression of the antigen recognized by MSN-1 is useful in selecting the high risk group out of patients with endometrial hyperplasia. Furthermore, we indicated that abnormal expression of the antigen recognized by MSN-1 associated with neoplasia of endometrial cells is useful in developing a new diagnostic method for example our endometrial cell enzyme immunoassay (EmC-EIA) and will be helpful in developing diagnostic approaches, such as missile therapy with a complex of MSN-1 and adriamycin for endometrial cancer.

Lipid analysis of Helicobacter pylori.

Lipids from Helicobacter pylori were extracted, isolated by conventional DEAE-Sephadex and silica gel column chromatography, and then purified by preparative thin-layer chromatography. Simple and phospholipids were analyzed by HPTLC and quantitatively determined by densitometry scanning. The fatty acid compositions of simple lipids were estimated by gas-liquid chromatography. The simple lipid composition of H. pylori consisted of wax ester (2.5%), triglycerides (4.9%), free fatty acids (30.0%), cholesterol (6.9%), diacylglycerol (29.1%), and monoacylglycerol (2.6%). The neutral phospholipid composition consisted of phosphatidyl ethanolamine (79.1%), lysophosphatidyl ethanolamine (16%), and phosphatidyl choline (1.9%). That of acidic phospholipids consisted of phosphatidic acid (52.7%) and phosphatidyl serine (47.3%). The major fatty acids of crude lipid, wax, free fatty acids, triglycerides, diacylglycerides, and monoacyl glycerides were C19:1 (cyclo), C18:2, C16:0, C19:1 (cyclo), C22h:0, and C18:0, respectively. These results are new findings and suggest significant characteristics from the metabolic, physiologic, and chemotaxonomic point of view.

Clinicopathological analysis of a patient with hypereosinophilic syndrome who demonstrated disseminated eosinophilic infiltration in various organs at autopsy.

A case (41 year old man) of idiopathic hypereosinophilic syndrome is presented. Typical eosinophilic endocarditis with restrictive cardiac failure and ventricular thrombosis was demonstrated by various clinical investigations, including cardiac pool scan and biopsy. The patient died after 22 months, and an autopsy revealed disseminated eosinophilic infiltration in the pancardium of the whole heart, aorta, main pulmonary artery, liver, and spleen.