Prognosis for papillary serous carcinoma of the endometrium after surgical staging.

BACKGROUND: To investigate the pattern of failure and the prognosis following pathological staging for uterine papillary serous carcinoma (UPSC). PATIENTS AND METHODS: A retrospective review was conducted of 22 patients with UPSC, treated between 1989 and 1998 at a single institution. All patients were surgically staged. Two patients with advanced disease received chemotherapy only. Two patients with early-stage disease were followed without further treatment. Eighteen patients received postoperative irradiation; eight patients received whole abdominal irradiation (WART), and the remaining 10 patients, pelvic irradiation (PRT). In addition, seven of these patients received vaginal cuff irradiation with low-dose-rate or high-dose-rate brachytherapy. Toxicity, pattern of failure, and survival were evaluated and compared to the literature. RESULTS: Seven patients (32%) developed distant metastases, three out of seven (42%) after WART. Four out of seven patients who had distant metastases died from disease progression during subsequent chemotherapy. All patients with distant metastases had locally advanced-stage disease at presentation (six stage III, one stage IV). Four patients with pelvic recurrences developed concurrent (2) and subsequent (2) distant metastases. Three patients had isolated distant metastases. No patient with early stage-disease (stage I and II) died from disease progression. CONCLUSION: Pathological staging should be performed for all patients with UPSC to determine the prognosis as well as to tailor the treatment. The role of abdominal irradiation in the treatment of UPSC is yet to be determined; however, such an approach may not be necessary for the control of disease for patients with early-stage (I and II) disease. Patients with locally advanced-stage (stage III) disease are at risk of local regional failures and distant metastases despite WART. Therefore, the benefit of WART for advanced-stage disease is also questionable. Paclitaxel-based chemotherapy is currently being investigated in this setting.

Monoclonal antibody DS6 detects a tumor-associated sialoglycotope expressed on human serous ovarian carcinomas.

A newly developed murine monoclonal antibody, DS6, immunohistochemically reacts with an antigen, CA6, that is expressed by human serous ovarian carcinomas but not by normal ovarian surface epithelium or mesothelium. CA6 has a limited distribution in normal adult tissues and is most characteristically detected in fallopian tube epithelium, inner urothelium and type 2 pneumocytes. Pre-treatment of tissue sections with either periodic acid or neuraminidase from Vibrio cholerae abolishes immunoreactivity with DS6, indicating that CA6 is a neuraminidase-sensitive and periodic acid-sensitive sialic acid glycoconjugate ("sialoglycotope"). SDS-PAGE of OVCAR5 cell lysates has revealed that the CA6 epitope is expressed on an 80 kDa non-disulfide-linked glycoprotein containing N-linked oligosaccharides. Two-dimensional non-equilibrium pH gradient gel electrophoresis indicates an isoelectric point of approximately 6.2 to 6.5. Comparison of the immunohistochemical distribution of CA6 in human serous ovarian adenocarcinomas has revealed similarities to that of CA125; however, distinct differences and some complementarity of antigen expression were revealed by double-label, 2-color immunohistochemical studies. The DS6-detected CA6 antigen appears to be distinct from other well-characterized tumor-associated antigens, including MUC1, CA125 and the histo-blood group-related antigens sLea, sLex and sTn.

Immunohistochemically detecting target antigens in patient biopsies for tailoring monoclonal antibody based cancer therapy.

Immunohistochemical analysis of biopsies, cytology specimens or surgical resection specimens using antibodies directed towards tumor-associated antigens, lineage or differentiation antigens is a technique often used by surgical pathologists to aid in establishing the correct histologic classification of malignant tumors. With the proliferation of experimental approaches to cancer treatment using monoclonal antibodies as targeting agents, it is anticipated that surgical pathologists will increasingly be receiving requests from clinicians to define the antigen profile in biopsy specimens, even when not necessary to render the correct tumor classification. Clinicians may use the immunohistochemically delineated antigen profiles provided by surgical pathologists to plan tailored treatment regimens utilizing monoclonal antibodies to the antigens expressed in the tumor biopsy to target anticancer therapeutic agents. Some of the potential problems in such a process might include the differing sensitivities, and perhaps specificities, of the antibodies used for analyzing the surgical pathology biopsy specimens compared to the monoclonal antibodies actually used in vivo. Our approach to this dilemma is to develop murine monoclonal antibodies to tumor-associated antigens that can reliably be used to detect antigens in routinely processed surgical pathology specimens as a starting point for further therapeutic monoclonal antibody development.

Embolectomy of a Bird's Nest Vena Caval Filter.

In this case report we describe a successful embolectomy of a partially migrated Bird's Nest Caval Filter with attached embolic material. We used transesophageal echocardiography to guide the surgical approach. The patient recovered uneventfully from both the embolectomy and the subsequent pelvic operation.

Responsiveness of human endometrial stromal cells to cytokines.

Cytokines are known to act in a variety of tissues, most commonly in a paracrine manner, to effect a number of biochemical processes. Previously, we found that human endometrial stromal cells respond to the action of interleukin-1 (IL-1) with an increase in the production of prostaglandins. In these investigations, we also found that IL-1 acts in endometrial stromal cells to stimulate the synthesis of IL-1 and IL-6 mRNA and protein. Specifically, in human endometrial stromal cells maintained in monolayer culture, treatment with IL-1 alpha leads to a striking increase in the synthesis of IL-1 beta mRNA and protein; this increase is IL-1 alpha-dose- and time-dependent. The pro-IL-1 beta produced, however, is not secreted into the culture medium but is retained within the stromal cell. The failure of secretion of IL-1 beta is characteristic of non-monocyte/macrophage cell types; this obtains because the enzyme that effects processing of pro-IL-1 beta (31 kDa) to the mature, secreted form of IL-1 beta (17 kDa) is believed to be present only in monocytes/macrophages. We also find that IL-1 and tumor necrosis factor-alpha (TNF-alpha) act in endometrial stromal cells to stimulate the synthesis of interleukin-6 (IL-6) mRNA and protein; the IL-6 produced by these cells is secreted into the culture medium. In addition, we find that IL-1 acts in endometrial stromal cells to inhibit the expression of mRNA for connexin43, a gap junction protein that is believed to be the principal component of gap junctions in cardiac and smooth muscle. Thus, it is likely that IL-1 action leads to a decrease in gap junction-dependent intercellular communication among endometrial stromal cells. Based on these findings, we conclude that endometrial stromal cells are responsive to the actions of IL-1 and TNF-alpha. These cells synthesize both IL-1 and IL-6; and, IL-6 is released into the extracellular medium. Thus, the possibility exists that the synthesis and action of cytokines may be involved in the mechanisms that serve to regulate the mesenchymal-epithelial interactions between endometrial stromal and glandular components; and, the formation and action of cytokines in decidua may serve to modulate immunological and infectious challenges encountered by this tissue in pregnancy.