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Biomedical subjects

W R Welch

Publications and source records attributed to W R Welch.

At least 55 records · Page 3Linked to original sources

Screening for ovarian cancer: the preliminary experience of a familial ovarian cancer center.

Women with a family history of ovarian cancer represent a high-risk group for the development of epithelial ovarian cancer. From July 1990 through December 1992, 386 women with a first-degree or multiple second-degree relatives with confirmed ovarian cancer were enrolled in a study to assess the utility of screening with transvaginal sonography, color flow doppler, and CA125. The mean age of the group was 41; 85% were premenopausal and 89/384 (23%) had 2 or more relatives with ovarian cancer. An initial ultrasound examination was abnormal in 89/384 (23%), 89% of whom were premenopausal. A persistent ovarian mass was detected in 15 patients and all were surgically proven to be benign. Mean CA125 levels were significantly higher and more variable in pre- vs postmenopausal women. CA125 was > or = 35 U/ml in 42/386 (11%) (36-232 U/ml). All but one of these women were premenopausal and 50% subsequently normalized. Two patients who were surgically explored for a rising CA125 had normal ovaries. An additional 19 patients have undergone prophylactic oophorectomy with no consistent histopathologic abnormality identified. These data demonstrate the difficulty inherent in screening a predominantly premenopausal population and do not clearly establish the efficacy of these modalities in the early detection of ovarian cancer.

Adult↗

Endoluminal thermal occlusion of the ureter with the electromagnetic field-focusing device.

The authors attempted ureteral occlusion by means of heat application in nine ureters (24 sites) of New Zealand White rabbits with the electromagnetic field-focusing (EFF) device. The EFF device generates heat at the tip of a grounded probe by focusing eddy currents that have been induced within the tissues by an external radio-frequency field. The power settings were varied from 30 to 150 W. Heat was applied at multiple sites in each ureter. Immediate functional occlusion was seen in all nine ureters. Long-term complete occlusion was seen in six ureters at power settings ranging from 40 to 150 W, while long-term partial occlusion was seen in two ureters at 30-50 W. All sites at 30 W resulted in partial occlusions. Perforation of the ureter resulted in urinoma formation in one ureter at a site that was treated with 150 W. The EFF device can be used to endoluminally occlude the ureter by causing a fibrotic reaction to thermal injury. The effective power range for this application appears to be 40-100 W.

Animals↗

Colouterine fistula complicating diverticulitis: charcoal challenge test aids in diagnosis.

Fistula formation between a segment of colon and the uterus is an unusual complication of diverticulitis; only 17 cases have been reported in the world literature. We describe a 69-year-old woman with a colouterine fistula secondary to diverticulitis. She presented with a malodorous vaginal discharge that grew multiple enteric organisms on culture. A barium enema revealed colonic diverticula but no fistula tract. Orally administered activated charcoal was seen flowing from the cervical os during a pelvic examination the following day, establishing a diagnosis of colouterine fistula. Pathologic examination of the resected colon and uterus confirmed this diagnosis and determined that diverticulitis was the etiology. From a review of the literature, we conclude that radiographic and invasive procedures cannot be depended upon for diagnosis. Ingestion of activated charcoal may provide a simple, noninvasive approach to the diagnosis of enterouterine fistulas.

Aged↗

Perineal exposure to talc and ovarian cancer risk.

OBJECTIVE: We sought to determine whether the use of talc in genital hygiene increases the risk for epithelial ovarian cancer. METHODS: We interviewed 235 white women diagnosed with epithelial ovarian cancer between 1984-1987 at ten Boston metropolitan area hospitals and 239 population-based controls of similar race, age, and residence. RESULTS: Overall, 49% of cases and 39% of controls reported exposure to talc, via direct application to the perineum or to undergarments, sanitary napkins, or diaphragms, which yielded a 1.5 odds ratio (OR) for ovarian cancer (95% confidence interval [CI] 1.0-2.1). Among women with perineal exposure to talc, the risk was significantly elevated in the subgroups of women who applied it: 1) directly as a body powder (OR 1.7, 95% CI 1.1-2.7), 2) on a daily basis (OR 1.8, 95% CI 1.1-3.0), and 3) for more than 10 years (OR 1.6, 95% CI 1.0-2.7). The greatest ovarian cancer risk associated with perineal talc use was observed in the subgroup of women estimated to have made more than 10,000 applications during years when they were ovulating and had an intact genital tract (OR 2.8, 95% CI 1.4-5.4); however, this exposure was found in only 14% of the women with ovarian cancer. CONCLUSIONS: These data support the concept that a life-time pattern of perineal talc use may increase the risk for epithelial ovarian cancer but is unlikely to be the etiology for the majority of epithelial ovarian cancers.

Adult↗

The influence of lactose consumption on the association of oral contraceptive use and ovarian cancer risk.

The authors investigated the joint effects of diet and oral contraceptive use on ovarian cancer risk in 194 white women aged 65 years or less with epithelial ovarian cancer and 193 age- and residence-matched controls in Boston between 1984 and 1987 by using in-person interviews and self-administered food frequency questionnaires. Use of oral contraceptives for 3 months or more was associated with a modest protective effect for ovarian cancer (odds ratio (OR) = 0.7, 95 percent confidence interval (CI) 0.5-1.1). In women who consumed 11 g or less per day of lactose, use of oral contraceptives for 3 months or more was associated with a nonsignificant increased risk (OR = 1.6, 95 percent CI 0.8-3.2). In women who consumed more than 11 g per day of lactose, use of oral contraceptives for 3 months or more was associated with a substantially decreased risk of ovarian cancer (OR = 0.3, 95 percent CI 0.1-0.7). Within this group, the strongest association occurred with more than 4 years of total oral contraceptive use (OR = 0.2, 95 percent CI 0.1-0.6) and in those who had more than 2 years of oral contraceptive use after age 30 years (OR = 0.1, 95 percent CI 0.03-0.4). These results suggest that, with respect to ovarian cancer, lactose users may be the most likely to benefit from oral contraceptive use and that the benefit may be strongest when oral contraceptive use occurs after age 30 years.

Adult↗

Tumor angiogenesis and metastasis--correlation in invasive breast carcinoma.

BACKGROUND: Experimental evidence suggests that the growth of a tumor beyond a certain size requires angiogenesis, which may also permit metastasis. To investigate how tumor angiogenesis correlates with metastases in breast carcinoma, we counted microvessels (capillaries and venules) and graded the density of microvessels within the initial invasive carcinomas of 49 patients (30 with metastases and 19 without). METHODS: Using light microscopy, we highlighted the vessels by staining their endothelial cells immunocytochemically for factor VIII. The microvessels were carefully counted (per 200x field), and their density was graded (1 to 4+), in the most active areas of neovascularization, without knowledge of the outcome in the patient, the presence or absence of metastases, or any other pertinent variable. RESULTS: Both microvessel counts and density grades correlated with metastatic disease. The mean (+/- SD) count and grade in the patients with metastases were 101 +/- 49.3 and 2.95 +/- 1.00 vessels, respectively. The corresponding values in the patients without metastases were significantly lower--45 +/- 21.1 and 1.38 +/- 0.82 (P = 0.003 and P less than or equal to 0.001, respectively). For each 10-microvessel increase in the count per 200x field, there was a 1.59-fold increase in the risk of metastasis (95 percent confidence interval, 1.19 to 2.12; P = 0.003). The microvessel count and density grade also correlated with distant metastases. For each 10-microvessel increase in the vessel count per 200x field, there was a 1.17-fold increase in the risk of distant metastasis (95 percent confidence interval, 1.02 to 1.34; P = 0.029). CONCLUSIONS: The number of microvessels per 200x field in the areas of most intensive neovascularization in an invasive breast carcinoma may be an independent predictor of metastatic disease either in axillary lymph nodes or at distant sites (or both). Assessment of tumor angiogenesis may therefore prove valuable in selecting patients with early breast carcinoma for aggressive therapy.

Adult↗

Induction of class II major histocompatibility complex antigen expression in human granulosa cells by interferon gamma: a potential mechanism contributing to autoimmune ovarian failure.

We investigated the possibility that major histocompatibility complex (MHC) class II antigens and interferon gamma, a product of activated T lymphocytes, play a role in human autoimmune oophoritis. MHC class II molecules initiate immune responses by presenting antigens to T-helper lymphocytes; interferon gamma can induce class II antigen expression at ectopic sites and has been implicated in the cause of various autoimmune disorders. We studied the expression of class II MHC antigens in ovaries from normal women of reproductive-age and from women with premature autoimmune ovarian failure. Immunoperoxidase technique applied to tissue sections of nine normal human ovaries revealed class II MHC antigen expression only on occasional cells of macrophage morphology; granulosa cells were negative regardless of stage of follicular maturation. In contrast, extensive and intense class II antigen expression was observed in granulosa cells in ovarian biopsy sections from four patients with premature autoimmune ovarian failure. Immunofluorescence and radioimmunoassay techniques used to detect and quantitate MHC antigens revealed that class II antigen expression could be induced and class I MHC antigen expression was enhanced in granulosa cell cultures after the addition of interferon gamma. These data provide evidence that autoimmune oophoritis is associated with ectopic expression of MHC class II antigens by ovarian granulosa cells, and that this phenomenon can be induced by the immunologic cytokine interferon gamma.

Adult↗

Antigenic heterogeneity in human ovarian cancer.

Primary and metastatic tumor tissues from 21 patients with ovarian epithelial cancer were studied with a panel of 8 monoclonal antibodies. Primary tumors reacted with 1 to 7 antibodies (mean, 3.5). Heterogeneity was observed even within histologic subtypes. Comparison of metastases (including ascites) with their respective primaries revealed differences in antigen profile in each of 10 cases studied. In one patient variable antigen expression was observed in five ascites samples collected over a 12-month period. These observations of antigenic heterogeneity and modulation with respect to site and time suggest that single monoclonal antibody immunotherapy would not be appropriate for all patients or even for a single patient over time.

Adenocarcinoma↗

Malignant mixed müllerian tumor of the ovary with prominent neuroectodermal differentiation (teratoid carcinosarcoma).

We report a unique carcinosarcoma of the ovary having an organoid growth pattern that resembled immature teratoma. The tumor contained both adenocarcinoma and squamous carcinoma (focally sebaceous) admixed with chondrosarcoma, rhabdomyosarcoma, and malignant neuroectodermal components. The neuroectodermal components were prominent, resembling ependymoblastoma, medulloepithelioma, ganglioneuroblastoma, glioblastoma multiforme, and pigmented neuroectodermal tumor. Immunohistochemical studies dramatically revealed carcinoma and rhabdomyosarcoma admixed with malignant neuroectodermal tumor. Implants of papillary serous carcinoma (with psammoma bodies) were present in the opposite ovary, uterine serosa, omentum, and appendiceal serosa. Although a variant not previously described in the ovary, this ovarian carcinosarcoma closely resembled nasopharyngeal tumors described as teratoid carcinosarcoma or terato-carcinosarcoma.

Carcinosarcoma↗

Multilocular peritoneal inclusion cysts (so-called cystic mesotheliomas).

Twenty-five cases of multilocular peritoneal inclusion cysts (MPIC) were investigated. All but four cases were associated with a history of a previous abdominal or pelvic operation, or evidence of endometriosis or pelvic inflammatory disease, or combinations of these findings. All of the lesions were attached to pelvic organs, 44% also occupied the upper abdominal cavity, and 16% involved the retroperitoneum. In three cases free-floating cysts were present as well. The median diameter of the lesions was 13 cm. The cyst locules were lined by one to several layers of flat to cuboidal mesothelial cells that occasionally formed papillae, had a hobnail shape, or had undergone squamous metaplasia. The stroma was characterized by chronic inflammation and often acute inflammation. In most of the cases there was mural proliferation of the mesothelial cells, occasionally simulating a malignant mesothelioma. Twelve lesions were complicated by postoperative local recurrence; in four of these cases the recurrences were multiple; neither the size of the lesion nor the presence of mural mesothelial proliferation influenced the outcome. The clinical and pathologic data in this series suggest that the MPIC is a nonneoplastic reactive mesothelial proliferation.

Adolescent↗

Galactose consumption and metabolism in relation to the risk of ovarian cancer.

In a case-control study, consumption of dairy foods by 235 white women with epithelial ovarian cancer and by 239 control women, and activity of red blood cell galactose-1-phosphate uridyl transferase (transferase) in a subset of 145 cases and 127 controls were determined. Yogurt was consumed at least monthly by 49% of cases and 36% of controls. The mean transferase activity of cases was significantly lower than that of controls. When a ratio of lactose consumption to transferase (L/T) was calculated, cases had a mean L/T of 1.17 compared with 0.98 for controls; there was a highly significant trend for increasing ovarian cancer risk with increasing L/T ratio. Lactose consumption may be a dietary risk factor and transferase a genetic risk factor for ovarian cancer.

Adult↗

Adenocarcinoma of the cervical stump.

Sixteen women with adenocarcinoma of the cervical stump were treated over a 15-year period. The median survivals of 40 months for stage IB and 17 months for stages II and III were significantly worse compared with those for patients treated for cervical adenocarcinoma of the intact uterus or squamous carcinoma of the cervical stump. The poor results were due to both local and distant failure. Implications regarding tumor radiosensitivity and adjuvant therapy in these high-risk patients are discussed.

Adenocarcinoma↗

Predictive factors for long-term survival in patients with advanced ovarian cancer.

A total of 107 patients with carcinoma of the ovary were entered in a study combining extensive primary surgery and intensive chemotherapy. Because of evidence supporting the effectiveness of both single agent platinum (P) and the combination of cyclophosphamide and doxorubicin (CA), patients were treated with alternating cycles of CA and CP. Primary surgery to remove the bulk of tumor to less than 2 cm was possible in 45% of the 85 eligible patients, and an additional 17% had similar surgery after two to four cycles of chemotherapy. Fifteen percent of patients progressed on chemotherapy. Of the 68 who were clinically and radiologically without disease at the completion of chemotherapy, 91% had second-look surgery. Forty-eight percent of these women had residual disease. All patients but one are at risk for greater than 60 months, with a median follow-up of 86 months. Overall 5-year survival is 26%, with a median survival of 33 months. Twenty patients survived over 5 years with 11 continuing to be free of disease (13% of all eligible patients). Patients with modified Broder's grade I,II tumors have not yet reached a median survival. Grade, stage, and primary mass size were the only variables with independent prognostic value in a Cox multivariate analysis.

Adult↗

Adenocarcinoma of the uterine cervix: prognostic factors and patterns of recurrence.

Survival data, prognostic factors, and patterns of recurrence were analyzed for 70 women with adenocarcinoma of the uterine cervix treated between 1968 and 1982. The 5-year survival rates for stages I, II, and III-IV were 82, 90, and 38%, respectively. Control of pelvic tumor was achieved in 82, 80, and 12.5% of cases of stage I, II, and III-IV disease, respectively. When radiation therapy techniques alone were employed, pelvic control was achieved in 100% of stage I and 75% of stage II cases. Tumor grade was an important prognostic factor in stage I disease, with 92% of patients with grade 1 and 2 lesions surviving 5 years, in contrast to 68% of patients with grade 3 lesions (P less than 0.05, log rank test).

Adenocarcinoma↗

Clear cell adenocarcinoma of the ovary: a clinical analysis and comparison with serous carcinoma.

Forty-four patients with clear cell adenocarcinoma of the ovary diagnosed between 1944 and 1981 were compared with a matched cohort of 55 patients with the most common epithelial malignant lesion, serous adenocarcinoma, in terms of their presentation and clinical course. None were lost to follow-up. Median follow-up was 9 years. Fifty percent of clear cell patients presented in Stage I versus 31% of serous patients. Patients with clear cell carcinoma presented more often with pelvic masses (84% vs 65%) and had larger (diameter greater than 10 cm) primary tumors (73% vs 29%). Forty-nine percent of clear cell patients were nulligravid compared with 24% of serous patients and endometriosis was strikingly more common in clear cell patients (58% vs 12%). When compared stage for stage, clear cell tumors were uniformly associated with poorer 5-year survival rates with an overall rate of 34%. In patients with recurrent disease, lymph node involvement was much more common in patients with clear cell carcinoma (40% vs 7%). Parenchymal organ involvement was also more common in the clear cell group (40% vs 13%). Ovarian clear cell adenocarcinoma has distinctly different clinical behavior compared to serous carcinoma and should be regarded as an aggressive epithelial histologic type.

Actuarial Analysis↗

Noncontraceptive estrogen use and epithelial ovarian cancer.

The relation of noncontraceptive estrogen use to epithelial ovarian cancer was evaluated in a case-control study conducted in hospitals mainly in the northeastern United States. There were 377 cases diagnosed within the year before hospital admission and 2,030 hospital controls; data were collected by interview in the hospital. Compared with women who never took noncontraceptive estrogens, the overall relative risk estimate for women whose estrogen use lasted at least one year and was not combined with progestogens or testosterone was 1.2 (95% confidence interval (CI) 0.8-1.9), after taking into account risk factors for ovarian cancer. There were 55 cases of the endometrioid, clear cell, or malignant mixed mesodermal cell type; the corresponding relative risk estimate was 0.9 (95% CI 0.3-3.0). There were 26 cases of undifferentiated cell type, with a relative risk estimate of 3.6 (95% CI 1.2-11). Relative risk estimates were similar in a subset of the cases (57%) for which pathology slides were reviewed. For estrogen use of long duration, use of high-dose preparations, or use in the distant past, the relative risk estimates were not significantly different from 1.0. The estimates were elevated for some categories of use, but not consistently--for example, for an interval of 5-9 years since estrogen use began (relative risk (RR) = 2.7), but not after shorter or longer intervals, and for use of conjugated estrogens with a dose of 0.3 mg (RR = 3.2) or 1.25 mg (RR = 2.4), but not for doses of 0.625 mg or 2.5 mg. The relative risk estimate was also elevated for use by nulliparous women (RR = 2.4). The results suggest that, overall, noncontraceptive estrogen use is not associated with the risk of epithelial ovarian cancer. Furthermore, our data do not support the hypothesis that estrogens increase the risk of endometrioid ovarian cancer. The elevated estimates could be due to multiple stratification of the data, but they should be explored in further studies, given the lethality of ovarian cancer and the common use of estrogens by postmenopausal women.

Adult↗

Ovarian clear cell carcinoma. A clinicopathologic analysis of 44 cases.

The clinical aspects and pathologic findings in 44 cases of pure clear cell carcinoma of the ovary are presented. The patients ranged in age from 28 to 78 years (mean, 50.6 years); 54% were nulliparous. Thirty-three percent of the patients had endometriosis in the involved ovary, and an additional 25% had endometriosis only in sites distant from the tumor. Microscopically, three architectural patterns (papillary, tubulocystic, and solid) and four cell types (clear, hobnail, eosinophilic, and flattened) were seen. A predominant tubulocystic architectural pattern was a good prognostic factor (p less than 0.01); however, no significant difference in survival by cell type was found. Grading of the tumors by conventional architectural and cytologic criteria had no predictive value for survival. Stage at presentation was the most important prognostic factor (p less than 0.001), with a 5-year overall survival of 34% and stage I survival of 55%. The poor stage I survival reflects the 15 patients (34%) in the study with stage Iaii lesions. In the 25 patients who developed recurrence, both distant organ involvement (40%) and lymph node involvement (40%) were frequent. Ovarian clear cell carcinoma has unusual pathologic and clinical features, and it represents a distinct histologic type of ovarian carcinoma.

Adenocarcinoma↗