Barbara A. Goff

Assessment of depth of myometrial invasion in endometrial adenocarcinoma

Depth of myometrial invasion in stage I adenocarcinoma of the endometrium is recognized as a prognostic factor for lymph node metastasis and overall survival. To determine if depth of myometrial invasion estimated by gross examination correlated with final histologic depth of invasion, we retrospectively reviewed all cases of surgical stage I endometrial adenocarcinoma treated at our institution between July 1985 and July 1988. Of the 113 evaluable patients, 63 had grade 1 lesions, 37 grade 2 lesions, and 13 grade 3 lesions. The depth of invasion was accurately determined by gross examination in 55 of 63 (87.3%) grade 1 lesions, 24 of 37 (64.9%) grade 2 lesions, and only 4 of 13 (30.8%) grade 3 lesions. Thus, gross examination of fresh tissue to estimate depth of myometrial invasion in endometrial adenocarcinoma is less reliable as the grade of the tumor increases. Alternative methods, such as frozen section, should be considered when evaluating depth of invasion, especially when this affects intraoperative decisions regarding lymph node sampling.

Effects of photodynamic therapy with topical application of 5-aminolevulinic acid on normal skin of hairless guinea pigs

Photodynamic therapy (PDT) is a relatively new approach to the treatment of neoplasms which involves the use of photoactivatable compounds to selectively destroy tumors. 5-Aminolevulinic acid (ALA) is an endogenous substance which is converted to protoporphyrin IX (PpIX) in the synthetic pathway to heme. PpIX is a very effective photosensitizer. The goal of this study was to evaluate the effect of PDT using topical ALA on normal guinea pig (g.p.) skin and g.p. skin in which the stratum corneum was removed by being tape-stripped (TS). Evaluation consisted of gross examination, PpIX fluorescence detection, reflectance spectroscopy, and histology. There was no effect from the application of light or ALA alone. Normal non-TS g.p. skin treated with ALA and light was unaffected unless high light and ALA doses were used. Skin from which the stratum corneum was removed was highly sensitive to treatment with ALA and light: 24 h after treatment, the epidermis showed full thickness necrosis, followed by complete repair within 7 d. Time-dependent fluorescence excitation and emission spectra were determined to characterize the chromophore and to demonstrate a build-up of the porphyrin in the skin. These data support the view that PDT with topical ALA is a promising approach for the treatment of epidermal cutaneous disorders.

Photoimmunotherapy and biodistribution with an OC125-chlorin immunoconjugate in an in vivo murine ovarian cancer model

Photodynamic therapy (PDT) is an experimental approach to the treatment of neoplasms in which photosensitisers (PSs) accumulated in malignant tissues are photoactivated with appropriate wavelengths of light. The target specificity of PSs may be improved by linking them with carrier macromolecules such as monoclonal antibodies (MAbs). OC125 is a murine MAb that recognises the antigen CA 125, which is expressed on 80% of non-mucinous ovarian tumours. A chlorin derivative conjugated to OC125 was shown to be selectively phototoxic to ovarian cancer and other CA 125-positive cells in vitro and ex vivo. We now report in vivo studies using an ascitic Balb/c nude mouse ovarian cancer model. Ascites was induced by intraperitoneal injection of cells from the human ovarian cancer cell line NIH:OVCAR3. Six weeks after injection, when the animals had developed ascites, biodistribution studies were carried out by injecting the immunoconjugate (IC) or free PS intraperitoneally and sacrificing the animals at 3, 6, 12, 24, 48, 72 and 168 h later. The PS was quantitated by extraction and fluorescence spectroscopy. For both the IC and free PS, peak tumour concentrations were reached at 24 h; however, the absolute concentrations for the IC were always higher (2- to 3-fold) than the free PS. Tumour to non-tumour ratios at 24 h for the IC were 6.8 for blood, 6.5 for liver, 7.2 for kidney, 5.7 for skin and 3.5 for intestine. Evaluation of viable tumour cells in ascites following in vivo PDT with a single light exposure demonstrated a dose-dependent relationship with fluence and IC concentration. However, there was significant treatment-related toxicity at all fluences. With multiple low-dose treatments, the percentage of viable tumour cells was also significantly reduced and there were no treatment-related deaths. These data suggest that, while photoimmunotherapy remains promising as a new treatment modality for ovarian cancers, careful quantitative dosimetry of both IC and light may need to be combined with multiple treatments (as with radiation therapy and chemotherapy) to control malignant disease yet maintain acceptable toxicity in vivo.

Combination chemotherapy in advanced adenocarcinoma of the fallopian tube

Abstract Advanced adenocarcinoma of the fallopian tube has a poor prognosis, with 5-year survival rates commonly less than 20%. Since 1980, we have managed 12 patients with disseminated tumor with combination chemotherapy following surgical cytoreduction. Analogous to the International Federation of Gynecology and Obstetrics staging of ovarian carcinoma, 3 patients were classified in Stage II, 8 in Stage III, and 1 in Stage IV. Ten patients received cisplatin-containing regimens. The 3 Stage II patients, without measurable disease after primary surgery, had an indeterminate response to chemotherapy. In Stages III–IV there were 4 complete responses (3 confirmed by second-look laparotomy) and 2 partial responses, for an overall response rate of 67%. Disease progressed in 2 patients and was stable in 1 patient. After median follow-up of 3.5 years, 4 of the Stage III–IV patients have no evidence of disease, 1 is alive with disease, and 4 are dead.

Endometrial Cancer: Screening, Diagnosis, and Surgical Staging

Through case studies, the authors point out environmental and hereditary factors that contribute to increased risk of developing endometrial cancer and how to apply screening modalities in pre- and postmenopausal women. Attention is drawn to certain anatomic abnormalities that prevent vaginal bleeding - the most common symptom related to cancer. Diagnostic tests that are available to pursue various aspects of the diagnosis in a sequential fashion are described, culminating in the endometrial biopsy. Recommendations for screening and diagnosis in the asymptomatic as well as the symptomatic patients are summarized. Surgical stag- ing represents the final event in the diagnostic workup. Instances when such staging can be modified to deal with various comorbidities are delineated.

Uterine leiomyosarcoma and endometrial stromal sarcoma: Lymph node metastases and sites of recurrence

Platlnmn-baaed ckemotkerapy of l&k-risk stage I epithelial ovariaa cancer followiag camprehensive surgical staging Rubin SC.; Wong G.Y.C.; Curtin J.P.; Barakat R.R.; Hakes T.B.; Hoskins W.J. USA OBSTET GYNECOL 1993 82/l (143-147) Objective: To determine the long-term outcome in patients with high-risk stage I epithelial ovarian cancer treated with adjuvant platinum-based chemotherapy following comprehensive surgical staging. Methods: We conducted a retrospective review of 62 patients with stage IA and IB (grades 2 or 3) and stage IC (all grades) epithelial ovarian cancer treated with platinum based chemotherapy following comprehensive surgical staging. Clinicopathologic correlations were performed using diseasefree survival as the end point. Results: The mean patient age was 47 years. The distribution by stage was IA in 19 (31%), IB in four (6%), and IC in 39 (63%). Eighty percent of the patients had grade 2 or 3 tumors. The distribution by cell type was as follows: clear cell 22 (35%). endometrioid 15 (24%), mutinous I I (18%). serous eight (13%), and undifferentiated six (10%). The patients underwent an average of six cycles of platinumbased therapy. With a median follow-up of 40 months among survivors, 15 patients (24%) have relapsed, at a median interval of 22 months from diagnosis. Relapses occurred primarily in the peritoneal cavity and retroperitoneal lymph nodes. No patient has been rendered free of disease after relapse. Patients with grade 3 tumors had an increased risk of relapse as compared to those with grade I or 2 tumors (46 vs. 8%; P = .002). Patients with clear-cell tumors had a higher risk of relapse than those with other cell types (41 vs. 15%; P = 0.05). There was no statistically significant relationship between risk of recurrence and substage. None of 11 patients with stage IA, grade 2 disease had recurrence. Actuarial 5-year disease-free survival for the entire group of 62 patients was 73%. Conclusion: Platinum-based chemotherapy for high-risk stage I ovarian cancer does not appear to improve survival over that previously reported with non-platinum regimens.