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C Bewtra

Publications and source records attributed to C Bewtra.

At least 19 recordsLinked to original sources
PubMed2000

Histology of prophylactically removed ovaries from BRCA1 and BRCA2 mutation carriers compared with noncarriers in hereditary breast ovarian cancer syndrome kindreds.

OBJECTIVE: The literature reports conflicting studies claiming premalignant histological features in benign ovaries from women who may have hereditary predilections for ovarian carcinoma. To test the veracity of these claims, this investigation studied ovaries prophylactically removed from members of hereditary breast ovarian cancer (HBOC) syndrome families who carry BRCA1 and BRCA2 mutations and compared these with the ovaries of mutation-negative women from the same HBOC syndrome kindred. METHODS: Sixty cases of women from HBOC syndrome families who had undergone prophylactic oophorectomies and whose BRCA1 and BRCA2 mutation status had been tested were selected from our database. Thirty had tested positive for BRCA1 mutations, 3 carried BRCA2 mutations, and 27 were negative for both BRCA1 and BRCA2 germline mutations. Histologic material from each case was examined by light microscopy blinded to the mutation status. Histologic features, previously reported to be possible precursor lesions for ovarian cancer, were quantified. Data from BRCA1 and BRCA2 mutation carriers were compared with those from mutation-negative cases in the direct line of genetic inheritance from the same HBOC syndrome families. RESULTS: Statistical analysis found that a more frequent occurrence of ovarian surface micropapillae in 87% of mutation carriers compared with just 55% of mutation-negative cases was the only histologic feature which was significantly different between the two groups (P = 0.39). Cortical clefts tended to be deeper in the ovaries of mutation carriers, but this did not reach significance (P = 0.051). There were no other significant histologic differences between the ovaries removed from mutation carriers and those from noncarriers. CONCLUSIONS: The results of our large and prospectively controlled, blinded study contrast with those reported from smaller, unblinded investigations. Except for the possible biological significance of surface micropapillae on ovaries from BRCA1 and BRCA2 mutation carriers, we found no histologic evidence for a genetically determined ovarian carcinoma precursor lesion.

Adult↗
PubMed1999

Microsatellite instability and expression of MLH1 and MSH2 in normal and malignant endometrial and ovarian epithelium in hereditary nonpolyposis colorectal cancer family members.

Mismatch repair deficiency is a characteristic molecular finding in hereditary nonpolyposis colorectal cancer (HNPCC), and has been demonstrated in both colorectal cancers and benign adenomas. Endometrial and ovarian cancers are common extracolonic tumors in this syndrome; however, few studies have investigated whether genetic changes occur in histologically normal endometrial and ovarian epithelia from HNPCC family members. If early genetic changes exist, they might be used as molecular markers to detect susceptibility to endometrial and ovarian cancers. In this study, we analyzed microsatellite instability (MSI) and MLH1 and MSH2 immunohistochemical expression in 20 histologically normal epithelia (12 endometrial and 8 ovarian) and 8 cancers (4 endometrial and 4 ovarian) obtained from 20 individuals representing 7 unrelated HNPCC families. While MSI was observed in endometrial (75%) and ovarian (100%) cancers, no case was determined to exhibit MSI in histologically normal epithelia of the endometrium or ovary. Similarly, in immunohistochemical expressions for MLH1 and MSH2, histologically normal epithelia had no genetic changes predisposing to malignancy. In cancer cases, a correlation existed between the expression of MLH1 and MSH2, the presence of germline mutations in the hMLH1 and hMSH2 genes, and the presence of tumor MSI. These data suggest that MSI and MLH1 and MSH2 expression are not useful biomarkers for the early detection of endometrial and ovarian malignancy in cancer-unaffected HNPCC germline mutation carriers. Further studies of other genetic changes in normal and premalignant precursor lesions are needed.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Clinicopathologic differences between diploid and tetraploid complete hydatidiform moles.

Complete hydatiform moles (CHM) may be are diploid or tetraploid. The proportions vary in the literature. To date, there has not been a systematic characterization of these two types. This study is a retrospective investigation of clinicopathologic differences between diploid and tetraploid CHMs. Thirteen formalin-fixed, paraffin-embedded CHMs were analyzed for DNA content by flow cytometry (FC). Using standard flow cytometric definitions, histograms were classified as FC-diploid or FC-tetraploid (4N peak > or = 15% of 2N peak and cell cycle events to 8N) and compared with respect to selected clinical and pathologic features. Eight CHMs (61%) met the criteria of tetraploidy by flow cytometry, although all five FC-diploid cases harbored minor (< 15%) tetraploid subpopulations. Patients with tetraploid moles were older (mean age 32.8 years vs. 19.6 years, p < 0.005), presented at lower preevacuation gestational ages (12.7 weeks vs. 15.4 weeks, p < 0.05), had higher mean serum beta-HCG levels (2.82 x 10(5) i.u. vs. 0.99 x 10(5) i.u., p = 0.07), and higher DNA S-phase fractions (17.9% vs. 7.0%, p = 0.002). No significant differences were found in other histological features. No moles recurred. In this small sample of CHMs, tetraploidy was common. Compared with the FC-diploid CHMs, FC-tetraploid CHMs occurred in older patients with lower gestational age, higher serum beta-HCG levels, and higher DNA S-phase fraction by flow cytometry.

Age Factors↗
PubMed1995

Prospective peer review in surgical pathology.

Quality assurance (QA) in surgical pathology has focused primarily on retrospective audits of randomly selected cases. The authors describe an effective method of prospective audit for a selected class of surgical specimens--diagnostic biopsies--and document the benefits, additional staff time required and impact on turnaround time. Additionally, these results were compared with a retrospective review. During a 6-month period, all diagnostic surgical pathology biopsies (n = 2,694, 55% of all cases) were reviewed by a second pathologist before release of the final report. Errors detected were subdivided into four categories: (1) major: errors in diagnosis that could directly affect patient care; (2) diagnostic discrepancies: errors in diagnosis that should not affect patient care; (3) minor: correct diagnosis rendered, but report correction required to add supportive information; (4) clerical: typographical and grammatical errors. Thirty-two major errors were found, involving 1.2% of cases reviewed. This manner of review caused an increase in overall turnaround time from 1.62 days to 1.79 days, and an increase in turnaround time for diagnostic biopsies from 1.44 days to 1.50 days. Time spent in performing prospective peer review averaged 4 hours per day. For comparison, results were included from a retrospective review performed on 480 of the 5,556 cases accessioned in a 6-month period before the institution of prospective quality assurance. This retrospective review revealed eight major errors (1.7%). In conclusion, the prospective peer review of diagnostic biopsies yields sufficient benefits in increased accuracy of diagnostic reports to justify the slight increase in additional work by pathologists.

Biopsy↗
PubMed1992

Columnar cells in posthysterectomy vaginal smears.

Columnar cells in posthysterectomy vaginal smears are unusual and rare. Nine such cases are reported here during a 6-yr period. All nine patients were asymptomatic and total hysterectomy with bilateral salpingoophorectomy for gynecological malignancies was performed 8 mo to 25 yr ago. Three patients had local radiation and one had systemic chemotherapy not less than 8 mo before the cytology. The columnar cells showed one of three patterns: 1) long, bipolar cells in sheets, resembling reparative columnar cells (4 cases), 2) goblet-type cells with eccentric nuclei (3 cases), and 3) tight clusters of small round cells (2 cases). No consistent relationship with age, treatment, or background was seen with any of the patterns. Follow-up of all cases by thorough pelvic examination, repeat smears, colposcopy, and biopsy showed no vaginal pathology. Benign mucinous or goblet cell metaplasia in atrophic vaginal epithelium may be the source of some of these cells in the vaginal smears.

Adult↗
PubMed1992

Hereditary ovarian cancer: a clinicopathological study.

Hereditary ovarian cancer (HOC) is rare and little recognized. Over the years, we have identified 37 HOC patients from HOC syndrome kindreds with documented cancers of ovary, breast, colon, or endometrium in two or more first-degree relatives. The age and clinical stage at diagnosis and overall 5-year survival of HOC patients were compared with those of ovarian cancers in the unselected patients. The gross and microscopic features of the tumors are compared with a set of 34 consecutively chosen ovarian cancer cases with documented negative family histories. The mean age of HOC patients at diagnosis was significantly lower (50.2 years) than that of the unselected control population (59 years) (p less than 0.001). Detailed pedigree analysis breaks down the HOC group into (a) site-specific ovarian cancer, 5 cases, 56.4 years mean age; (b) breast-ovarian cancer syndrome, 28 cases, 50.46 years mean age; and (c) Lynch syndrome II (colon/endometrial cancer), 4 cases, mean age 41 years. The age differences were statistically significant (p = 0.050). The most prevalent International Federation of Gynecology and Obstetrics clinical stage at diagnosis of HOC (stage III) was the same as for the control group. Histologically, all (100%) HOC tumors were surface epithelial cancers with predominance of serous papillary type moderate to high grade (89 versus 71% in control, p = 0.07). No other pathologic features appeared to be significant. In conclusion, HOC is a serous papillary tumor and characterized by early age of onset and excess of breast/ovary/colon-endometrial cancers in first-degree relatives of patients with specific HOC syndromes.

Adult↗
PubMed1992

Long-term cultured mouse mast cells: ultrastructure, histamine and leukotriene levels.

Interleukin 3 (IL3), dependent cells were obtained from bone marrow (9/10 experiments) and spleen cells (4/5 experiments), but not from the thymus. These cells were similar to mucosal mast cell toluidine blue staining and electron microscopy. They had heterogenous metachromatic granules, and some had large scroll-like structures. They also contained histamine (200-800 ng/10(6) cells) for the first 2-5 weeks, whose level diminished to less than 30 ng/10(6) cells by 10 weeks of culture. They also generated leukotriene (LT) C4/D4 (10-40 ng/10(6) cells) and LTB4 (2-5 ng/10(6) cells) for over 100 days of culture. In one experiment, bone marrow-derived mast cells after 150 days of culture began to produce an IL3-like substance and proliferated exponentially without exogenous IL3.

Animals↗
PubMed1991

Hereditary ovarian cancer. Heterogeneity in age at diagnosis.

An unknown fraction of the ovarian cancer burden occurs in women with a family history indicative of a putative autosomal dominantly inherited cancer susceptibility syndrome. The results from a five-generation, extended, hereditary breast-ovarian cancer kindred are described 10 years after it was initially ascertained. Significantly more cancers were observed in high-risk family members during this decade than were expected (P less than 0.001). The age of ovarian cancer diagnosis was studied in additional ovarian cancer-prone families of three types: site-specific ovarian cancer syndrome, the breast-ovarian cancer syndrome, and Lynch syndrome II. The age of onset in each of the three sets was significantly (P less than 0.001) earlier than the general population mean of 59, and there were significant differences in the age of onset (P = 0.050) among these three cohorts. Ovarian cancer histology was similar to that of patients with negative family histories. There may be clinically significant heterogeneity in the age at diagnosis of ovarian cancer among these ovarian cancer-prone syndromes. This has important implications for understanding its natural history and targeting surveillance-management strategies.

Adult↗
PubMed1990

Evaluation of a continuous combined low-dose regimen of estrogen-progestin for treatment of the menopausal patient.

Menopause constitutes a sizable proportion of the adult women's life, and it is reasonable to consider that most women will benefit from hormone-replacement therapy. Also, it is important to realize that cardiovascular disease is a major cause of morbidity and death in the menopausal patient. Two regimens of hormone-replacement therapy were evaluated in postmenopausal women with 0.625 mg of conjugated equine estrogen with either 2.5 or 5 mg of medroxyprogesterone acetate taken continuously for 52 weeks in 92 patients. The data demonstrated an improvement in menopausal symptoms, a beneficial effect in lipoprotein profiles, the establishment of an atrophic endometrium, and a marked decrease in vaginal bleeding after 13 weeks and a further decrease after 26 weeks. Ideally this regimen will offer better patient compliance and, if the favorable lipoprotein profiles offer protection to the cardiovascular system, the overall health of the American woman will be markedly affected.

Cholesterol↗
PubMed1990

Hereditary carcinoma of the ovary and associated cancers: a study of two families.

Increasing attention has been given to host factors in the etiology of ovarian carcinoma. Case/control studies have shown a significant excess of this disease among primary relatives of ovarian cancer affected. Pedigree studies have demonstrated its occurrence on a site-specific basis, in association with carcinoma of the breast (breast/ovarian carcinoma syndrome), and in other hereditary disorders. The complexity of this heterogeneity clearly warrants more intensive family studies. We have described genetic and clinicopathologic nuances in two extended ovarian cancer-prone families. The absence of premonitory physical stigmata and/or biomarkers which signify the cancer-prone genotype compels the physician to employ the best posits from the pedigree to identify those patients who are at inordinately high risk for ovarian and/or syndrome-associated cancer so that surveillance strategies can be more focused. Because of limitations of current surveillance strategies for the early detection of ovarian carcinoma, the clinician's responsibility includes the identification and counseling of candidates for prophylactic oophorectomy.

Adult↗
PubMed1988

Cyclic endometrial changes: US assessment with histologic correlation.

The ultrasonographic (US) appearance of the endometrium was evaluated in 80 patients, and the US diagnosis of endometrial stage was compared with that from same-day endometrial biopsy specimens. The US signs of proliferative endometrium included triple-line sign, hypoechoic function layer, and minimal or absent posterior acoustic enhancement. The signs of secretory endometrium included absent triple-line sign, hyperechoic functional layer, and strong posterior acoustic enhancement. When all of these US signs were clearly depicted in combination, the accuracy of diagnosis was 93% (30 patients). The accuracy of diagnosis for all patients in the study was 76% (73 patients). The relative distributions of each US sign in proliferative and secretory endometrium were compared. Despite complicating extrinsic factors such as uterine leiomyomas and intrinsic factors such as the transition period between endometrial phases, US staging of the endometrium is a useful diagnostic technique that allows serial examinations of the endometrium.

Adult↗
PubMed1988

Endometrial histology and bleeding patterns in menopausal women treated with estrogen and continuous or cyclic progestin.

Thirty-six postmenopausal women were randomized to three groups in a double-blind, prospective study. All were treated for three months with conjugated estrogens (Premarin), 0.625 mg daily, and three different doses of a progestin (Provera), 2.5 mg daily, 5 mg daily or 5 mg during the last 12 days of a 28-day cycle. We found that the endometrium was maintained in an inactive phase in 100% of the women given continuous daily progestin but in only 25% of those given cyclic progestin. Bleeding occurred in 100% of subjects given cyclic progestin and in 50% of those given continuous progestin; however, bleeding episodes diminished with time in those on continuous progestin. A hormonal regimen that leads to reduced or absent bleeding and an inactive endometrium is preferable for postmenopausal women if estrogen therapy is to be used for the long term after menopause.

Antineoplastic Agents↗
PubMed1987

Malignant fibrous histiocytoma of the heart. A case report and review of the literature.

A case report of a 28-year-old woman with malignant fibrous histiocytoma (MFH) of the left atrium is presented, and the six previous reports of this rare cardiac tumor are reviewed. A tendency for malignant fibrous histiocytoma of the heart to occur in the left atrium of young women is suggested; this sarcoma's usual location is in the soft tissue of elderly men. The apparent predilection for the left atrium is unique among cardiac malignancies. Careful pathologic study is necessary to differentiate the uniformly fatal MFH of the heart from the more common benign atrial myxoma.

Adult↗
PubMed1987

Cystic adventitial degeneration of the femoral artery: is evacuation and cyst excision worthwhile as a definitive therapy?

A case of cystic adventitial degeneration of the left common femoral artery in a patient with localized left groin pain, normal distal pulses, and normal arteriographic findings is reported. This patient was first treated with evacuation and cyst excision. Recurrence was noted after 20 months, and an excision of the cyst and a segment of the common femoral artery with graft interposition was required. At gross examination, the cyst was unilocular and contained gelatinous material. The cyst appeared to be situated in the tunica adventitia and did not communicate with the vascular lumen. No synovial lining was present. Histologically, it was similar to a ganglion cyst with contents rich in hyaluronic acid. A review of the literature was undertaken to determine the results of treating this lesion. The disease is rare. All senior authors of case reports were contacted to construct follow-up information. A high incidence of recurrence was noted in patients treated by evacuation and cyst excision. We believe that total cyst excision with the involved artery and graft interposition at the femoral site can be done easily, safely, and with virtually no chance for recurrence.

Arterial Occlusive Diseases↗
PubMed1986

Familial ovarian carcinoma. Clinical nuances.

Familial ovarian carcinoma has been recognized with increased frequency during the past decade commensurate with physician attention to family history. Putative autosomal dominant inheritance of this heterogeneous problem mandates attention to both paternal and maternal lineages. A family with probable paternal transmission of breast/ovarian carcinoma is presented. One family member had findings consonant with papillary serous adenocarcinoma of ovarian origin, which may have arisen directly from extra-ovarian pelvic mesothelium. These and other clinical nuances of familial ovarian carcinoma are discussed in order to aid physicians in understanding the natural history, surveillance, and management of familial ovarian carcinoma.

Adult↗
PubMed1986

Familial peritoneal ovarian carcinomatosis: a new clinical entity?

A familial form of ovarian carcinoma is now widely recognized. There are at least several ovarian cancer-prone genotypes, consistent with genetic heterogeneity. Prophylactic oophorectomy has been employed for women who were judged to be at 50% risk for this disease by virtue of their position in the pedigree. However, recent evidence has disclosed that a fraction of such patients who underwent prophylactic oophorectomy and who had ovaries which appeared to be histologically normal at surgical resection, subsequently developed intraabdominal carcinomatosis with histologic findings showing the lesions to be indistinguishable from ovarian carcinoma. Given the embryologic derivatives of the ovary, which comprise gonadal ridges composed of mesodermal cells covered by coelomic epithelium, we postulate that patients with hereditary predisposition to ovarian carcinoma harbor the first germinal hit in both the epithelial cells of the ovary as well as their derivatives in the coelomic mesothelium. These patients may then be inordinately susceptible to carcinogenesis from the second (somatic) hit in these same tissues.

Adenocarcinoma, Papillary↗