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Biomedical subjects

R C Bentley

Publications and source records attributed to R C Bentley.

At least 37 records · Page 2Linked to original sources
PubMed1999

Epidemiologic and surgicopathologic findings of papillary serous and clear cell endometrial cancers when compared to endometrioid carcinoma.

PURPOSE: The aim of this study was to identify similarities and differences in epidemiologic and surgicopathologic staging results for papillary serous (PS) and clear cell (CC) endometrial cancers compared with endometrioid (EM) carcinoma of the endometrium. METHODS: Clinical and surgicopathologic data were retrospectively collected on 574 clinical stage I-II endometrial cancer patients, including 53 PS and 18 CC (based on postoperative histology), undergoing hysterectomy at Duke University Medical Center between 1967 and 1990. All staging material was available and reexamined prior to this analysis, and FIGO surgical staging was retrospectively assigned. PS and CC histologic subtypes were compared both as a common category and as discrete categories versus EM, EM grade 1 (EM1), EM grade 2 (EM2), and EM grade 3 (EM3). Fisher's exact test was used to compare proportions with unordered categories (2x2 tables), while the chi(2) test for trend was used to compare proportions in 3x2 tables with ordered categories. Differences in medians were compared with the Wilcoxon rank-sum test. RESULTS: PS tumors accounted for 8%, CC for 2%, and EM for 90% of cases. Overall, 14% of tumors were changed to a different postoperative histology including 64% of PS, 50% of CC, and 8% of EM. Postoperative histology changes were 4% for EM1 and 21% for EM3. PS, CC, and EM3 had more surgical sampling performed than for other EM. Rates for lymph node dissections were similar for EM3 (81%), PS (72%), and CC (67%) tumors, although metastases were more frequent for PS and CC compared with EM3. When PS tumors were confined to the endometrium, paraaortic metastases occurred in 13%. LVSI increased with EM grade and was highest for PS and CC. Upstaging to surgical stage III-IV occurred in 47% of PS, 39% of CC, and 12% of EM. The majority of PS and CC tumors were confined to the inner one-third of the myometrium, compared with EM tumors, where grade correlated with depth of myometrial invasion. Extrauterine metastases occurred in 55% of PS and 45% of CC tumors confined to the inner one-half, compared with 17% of EM3. CONCLUSION: Frequent changes from preoperative to postoperative histology and grade may contribute to misassignment of preoperative and intraoperative risk as determined by depth of myometrial invasion for PS and CC patients. The higher frequency of extrauterine metastases in PS and CC tumors compared with EM3, despite similar surgical sampling rates, supports a more virulent behavior. The poor correlation between depth of myometrial invasion and risk for extrauterine metastases helps to explain poorer survival in PS and CC patients, in addition to more frequent upstaging. These results support routine extended surgical staging for women with preoperative or intraoperative diagnosis of PS and CC tumors. Intraoperative assessment of tumor grade and histology may be indicated and warrants further investigation.

Adenocarcinoma, Clear Cell↗
PubMed1999

Malignant melanoma presenting as a mediastinal mass.

A case of malignant melanoma presenting as a mediastinal mass without an extrathoracic primary is reported. Microscopically the tumor appeared consistent with malignant melanoma, with the presence of focal melanin pigment in large epithelioid cells. Fontana stain confirmed the presence of melanin pigment. Immunohistochemical staining further suggested melanoma, with the tumor cells expressing a HMB45+, S100+ and cytokeratin-phenotype. Electron microscopy showed an abundance of melanosomes confirming the diagnosis of malignant melanoma.

Aged↗
PubMed1999

Calpain mediates ischemic injury of the liver through modulation of apoptosis and necrosis.

BACKGROUND & AIMS: Calpain proteases have been implicated in cell death by necrosis and more recently by apoptosis. Experiments were designed to determine the role of calpain proteases in ischemic rat liver injury by measurement of cytosolic calpain activity after different periods of ischemia-reperfusion and by evaluation of the effects of calpain inhibition on tissue injury and animal survival. METHODS: Calpain activity was measured in the cytosol using Suc-Leu-Leu-Val-Try-7 amino-4 methyl coumarin, a specific fluorogenic substrate, and Cbz-Leu-Leu-Tyr-CHN2, a specific inhibitor. RESULTS: Calpain activity increased significantly with the duration of ischemia-reperfusion and was inhibited more than 80% by the inhibitor. Calpain inhibition resulted in a significant decrease in transaminase release and tissue necrosis and converted nonsurvival ischemic conditions to survival conditions. When the in situ terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-digoxigenin nick-end labeling assay for apoptosis was used, 35% +/- 6% of nonparenchymal cells and 16% +/- 3% of hepatocytes stained positively after 60 minutes of ischemia and 6 hours of reperfusion. In contrast, animals pretreated with the calpain inhibitor showed minimal evidence of apoptosis. This was further substantiated by gel electrophoresis assay for DNA fragmentation and by electron-microscopic evaluation. CONCLUSIONS: These data suggest that calpain proteases play a pivotal role in warm ischemia-reperfusion injury of the rat liver through modulation of apoptosis and necrosis.

Alanine Transaminase↗
PubMed1999

Focal fibrosis: a common breast lesion diagnosed at imaging-guided core biopsy.

OBJECTIVE: Focal fibrosis is a benign breast lesion commonly diagnosed by imaging-guided core biopsy. The goal of this study is to determine the frequency of focal fibrosis diagnosed at core biopsy and to describe its imaging features. MATERIALS AND METHODS: A consecutive series of 894 imaging-guided breast core biopsies were reviewed, and all cases of focal fibrosis were selected. The imaging features of each lesion were characterized. All lesions had been reviewed during radiologic-histologic review sessions to assess for accurate needle positioning and concordant results. Follow-up imaging and histologic data were reviewed to document lesion stability. RESULTS: Focal fibrosis was diagnosed in 80 (8.9%) of 894 imaging-guided core biopsies: 20 (8.7%) of 229 sonographically guided biopsies and 60 (9.0%) of 665 mammographically guided biopsies. Of 75 mammographically visible lesions, 39 (52%) were masses, 29 (39%) were densities, and seven (9.3%) were clusters of calcifications. Thirty-five hypoechoic lesions were visualized on sonography: 29 (80%) were oval, and six (17%) were irregularly shaped. Six (21%) of the 28 oval masses showed posterior enhancement, four (14%) posterior shadowing, and 19 (68%) neither feature. Fifty-two (65%) of 80 patients with focal fibrosis had routine imaging follow-up; all had stable findings (mean follow-up period, 27 months). No false-negative cases were identified. CONCLUSION: Focal fibrosis most commonly appears as an enlarging solid mass or developing density on mammography or as an oval mass on sonography. Our data suggest that focal fibrosis accounts for 9% of lesions that undergo imaging-guided core biopsy and that the diagnosis can be accurately reached using imaging-guided biopsy.

Adult↗
PubMed1999

Pseudoanaplastic giant cell tumor of bone.

Marked nuclear atypia can be found in a variety of benign mesenchymal tumors, including ancient schwannomas, symplastic leiomyomas, osteoblastomas, and chondromyxoid fibromas. Such nuclear atypia is believed to represent a degenerative phenomenon and does not indicate aggressive behavior. Separation of these pleomorphic but benign lesions from true sarcomas may be difficult. We are aware of only one prior description of such degenerative atypia in benign giant cell tumor of bone. We report a benign giant cell tumor of bone arising in the sacrum of a 21-year-old white female. Preoperative embolization of this lesion had been performed, and subsequent curetting revealed marked atypia suggestive of an anaplastic malignancy. However, only very rare mitotic figures were present, and the radiographs were consistent with a benign giant cell tumor. A diagnosis of benign giant cell tumor was made, and no recurrence or metastases have been observed during the 4-year postoperative period.

Adult↗
PubMed1998

Mutation of the PTEN tumor suppressor gene in endometrial hyperplasias.

Mutation and deletion of the PTEN tumor suppressor gene occurs in about 40% of endometrial carcinomas. The purpose of this study was to determine whether PTEN mutations also are present in endometrial hyperplasias, which are premalignant precursors of invasive endometrial adenocarcinomas. Genomic DNA from 51 endometrial hyperplasias was extracted from paraffin blocks, and PCR was used to amplify the nine exons of the PTEN gene. These products were screened using single-strand conformation analysis, and variant bands were sequenced. Somatic mutations in the PTEN gene were seen in 10 of 51 cases (20%), and two mutations were found in one case. An identical 4-bp deletion in exon 8 was seen in three cases, and 8 of 11 PTEN mutations predicted truncated protein products. There was no higher frequency of PTEN mutations in endometrial hyperplasias with atypia (6 of 32; 19%) relative to those without atypia (4 of 19; 21%). These data suggest that inactivation of the PTEN tumor suppressor gene is an early event in the development of some endometrial cancers.

Endometrial Hyperplasia↗
PubMed1998

Apoptosis of sinusoidal endothelial cells is a critical mechanism of preservation injury in rat liver transplantation.

In livers excised for transplantation, sinusoidal endothelium appears especially vulnerable to injury during organ preservation in the cold and subsequent reperfusion. The degree of endothelial cell injury correlates with functional impairment of the graft following transplantation. The mechanism of injury remains obscure, but endothelial cell damage has been described as coagulative necrosis secondary to irreversible physico-chemical damage. We investigated whether endothelial cell death is caused by apoptosis rather than by necrosis. Tissue from rat livers stored for varying periods in cold (1 degree C) Euro-Collins solution and then reperfused for 1 hour at 37 degrees C were studied for evidence of apoptosis by detection of DNA fragmentation using the in situ terminal deoxynucleotidyl transferase d-uridine triphosphate nick end labeling (TUNEL) assay, DNA gel electrophoresis, and by transmission electron microscopy (EM). DNA fragmentation of the type characteristic of apoptosis was identified in 49.7% +/- 2.2% of sinusoidal lining cells after 8 hours of ischemia + reperfusion (viable graft) vs. 70.7% +/- 4.3% after 16 hours + reperfusion (nonviable graft) (P < .001). No such fragmentation was observed after cold preservation without reperfusion or in unpreserved, reperfused livers. EM demonstrated changes characteristic of apoptosis exclusively in endothelial cells. The study suggests that the apoptosis of sinusoidal endothelial cells is a pivotal mechanism of preservation injury in liver transplantation.

Animals↗
PubMed1998

Villoglandular adenocarcinoma of the endometrium: a clinicopathologic study of 61 cases: a gynecologic oncology group study.

Papillary endometrioid or villoglandular adenocarcinoma (VGA) is a relatively common type of endometrial adenocarcinoma, but studies describing its behavior have yielded conflicting results. Patients with a component of VGA were identified in a review of 819 women entered in a Gynecology Oncology Group Study (Protocol 33) of clinical stages I and II endometrial adenocarcinoma. Cases with coexisting foci of serous or clear cell carcinoma were excluded from further consideration. Of the 61 cases that formed the study sample, there were 24 with pure villoglandular differentiation and 37 who were admixed with typical endometrioid adenocarcinoma (EA). The general clinicopathologic features of patients with pure and mixed VGA are compared with 469 patients with pure EA. The VGAs were better differentiated (grade 1 or 2--97% of VGA versus 74% EA, p = 0.001). but they were not significantly different with respect to median age, depth of invasion, or frequency of nodal spread. Six of the 61 patients with VGA died of their tumor. The disease-specific survival rate at 3 years for VGA is 94% (95% confidence interval: 0.88-0.99) compared with 88% (95% CI: 0.86-0.91) for EA. Two of the patients who died had pure villoglandular tumors and four had mixed villoglandular and endometrioid carcinoma. In view of the frequent admixture of VGA and EA and their generally similar biological characteristics, with a prognosis similar to that of typical EA, we conclude that VGA should be considered a variant of EA.

Adenocarcinoma, Mucinous↗
PubMed1998

Goblet-cell mucinous epithelium lining the endometrium and endocervix: evidence of metastasis from an appendiceal primary tumor through the use of cytokeratin-7 and -20 immunostains.

Differential staining with cytokeratin (CK)-7 and CK-20, two members of a complex family of proteins in human epithelial cells, proved critical in showing that the extremely well-differentiated goblet-cell (intestinal) mucinous epithelium lining the surface of the endometrium and endocervix in two patients and the fallopian tube in one was identical to that of the coincident appendiceal neoplasms. One of these patients also had a large ovarian tumor that grossly and microscopically resembled a mucinous cystadenoma of borderline malignancy and would have been considered primary except for the CK stains (CK-20 positive and CK-7 negative), which suggested metastasis from the appendix, presumably by a transtubal route.

Appendiceal Neoplasms↗
PubMed1997

Antiangiogenic agents protect liver sinusoidal lining cells from cold preservation injury in rat liver transplantation.

BACKGROUND & AIMS: Low temperature preservation causes unique liver injuries to the sinusoidal lining cells characterized by endothelial cell detachment and rounding and Kupffer cell activation. These changes are similar to those observed during the early stages of angiogenesis. The aim of this study was to investigate if cold preservation injury is caused by the activation of angiogenic mechanisms. METHODS: Livers were obtained from rats pretreated with three well-known antiangiogenic agents (minocycline, interferon alfa-2b, and fumagillin) and were stored for various durations in cold preservation solutions. The effects of the drugs were evaluated by morphometric assessment of endothelial cell injury in H&E, trypan blue, and immunostained (TIE2/Tek) biopsy specimens. Graft functions and survival were evaluated in isolated perfused rat liver and arterialized orthotopic liver transplantation models. RESULTS: Sinusoidal lining cell integrity and viability were significantly improved in animals pretreated with the drugs. Reperfusion injury and survival were also better in pretreated animals. Interferon alfa was the most potent agent, reducing injury even in livers preserved in the current most commonly used solution (University of Wisconsin solution). CONCLUSIONS: Cold preservation injury of liver may be the results of angiogenic mechanisms. This novel observation provides a rationale for improved liver preservation using antiangiogenic agents.

Adenosine↗
PubMed1997

Gastric graft-versus-host disease: a blinded histologic study.

Acute graft-versus-host disease (GvHD) of the upper gastrointestinal (GI) tract is common after allogeneic bone marrow transplantation (BMT). However, diagnosis cannot be made on clinical presentation and endoscopic findings alone, because these are nonspecific, and histologic confirmation is often desirable. The diagnosis of gastric GvHD is often based on subtle findings with considerable potential for variability in interpretation. Evaluation of the reproducibility of diagnosis and recognition of histologic features of gastric GvHD was based on blinded review of 56 gastric biopsies (24 from patients with allogeneic BMT or unrelated umbilical cord blood transplantation and 32 control biopsies from patients who did not undergo BMT, of whom eight had active GI cytomegalovirus [CMV] infection). Histologic criteria for GvHD were apoptosis and gland destruction, sparse inflammatory infiltrate, and granular eosinophilic debris in dilated glands. Seventeen patients (22 biopsies) were judged to have clinical GvHD on the basis of skin or liver involvement and GI symptoms without other known cause. Eighteen of these 22 gastric biopsies were classified as GvHD by at least two of the three pathologists on initial review. Blinded histologic diagnosis of GvHD had a positive predictive value of 69%, a sensitivity of 82%, and specificity of 76%. False-positive results occurred in CMV gastritis, human immunodeficiency virus (HIV) infection, primary immunodeficiency, and after renal transplantation. Of individual features, granular debris in glands was a specific (94% specificity), but insensitive (41% sensitivity) marker for GvHD. Distinction between GvHD and CMV infection can be difficult, and GvHD can be confused with changes seen in HIV infection and other immunodeficiency states.

Adolescent↗
PubMed1997

Signet-ring cell carcinoma of the endometrium: a primary tumor masquerading as a metastasis.

Extragenital metastases to the endometrium are unusual, but several histologic features have been suggested as highly suggestive or even pathognomonic for this diagnosis. We report an endometrial carcinoma with a prominent signet-ring cell morphology and a diffusely permeative pattern of infiltration, features that have been reported as indicating an extragenital metastasis. To the best of our knowledge, this is the first reported case of a signet-ring cell carcinoma of the endometrium. Gynecological pathologists should be aware of this entity because of its potential primary of metastatic signet-ring carcinoma to be endometrium.

Aged↗
PubMed1997

The detection of breast microcalcifications with medical ultrasound.

Microcalcifications are small crystals of calcium apatites which form in human tissue through a number of mechanisms. The size, morphology, and distribution of microcalcifications are important indicators in the mammographic screening for and diagnosis of various carcinomas in the breast. Although x-ray mammography is currently the only accepted method for detecting microcalcifications, its efficacy in this regard can be reduced in the presence of dense parenchyma. Current ultrasound scanners do not reliably detect microcalcifications in the size range of clinical interest. The results of theoretical, simulation, and experimental studies focused on the improvement of the ultrasonic visualization of microcalcifications are presented. Methods for estimating the changes in microcalcification detection performance which result from changes in aperture geometry or the presence of an aberrator are presented. An analysis of the relative efficacy of spatial compounding and synthetic receive aperture geometries in the detection of microcalcifications is described. The impact of log compression of the detected image on visualization is discussed. Registered high resolution ultrasound and digital spot mammography images of microcalcifications in excised breast carcinoma tissue and results from the imaging of suspected microcalcifications in vivo are presented.

Breast↗
PubMed1997

Malignant supratentorial glial-neuronal neoplasms: report of two cases and review of the literature.

OBJECTIVE: Malignant neoplasms exhibiting mixed populations of neuronal and glial cells occurring in the cerebral hemispheres of young adults and children are well recognized, but rare. A confusing array of diagnostic terms has arisen. We describe two patients with such tumors and review the literature concerning these interesting cases. PATIENTS: A 21-year-old man and a 5-year-old girl presented with large, cystic, intracerebral lesions on magnetic resonance images, which proved to be composite neoplasms exhibiting malignant neurons and astrocytes. RESULTS: The 21-year-old man had a frontal lobe mass with enhancing and nonenhancing regions, which corresponded to cerebral neuroblastoma and anaplastic astrocytoma, respectively. The presence of occasional microtubules and rare primitive presynaptic processes, accompanied by antisynaptophysin immunoreactivity, established the neuronal nature of the cells in the enhancing region. The nonenhancing region was composed of a moderately cellular neoplasm of fibrillar astrocytes that were mitotically active. The 5-year-old girl presented with a left parietal lobe neoplasm, which histologically was composed of lobular proliferations of neuroblasts and glia. The neuroblastic populations exhibited evidence of maturation with small anaplastic cells, spindle-shaped cells, and large dysmorphic ganglion cells. The glial tumor showed both well-differentiated fibrillary astrocytes with microcysts and anaplastic populations with central necrosis and pseudopalisading. CONCLUSIONS: Present classification systems devised to describe mixed neuronal and glial tumors do not adequately encompass the diversity of morphologies presented by these two cases. We conclude that the terms cerebral neuroblastoma-anaplastic astrocytoma for case 1 and cerebral ganglioneuroblastoma-glioblastoma for case 2 are preferred because they convey useful clinical information by reflecting concepts already encompassed by the World Health Organization's classification system of tumors of the central nervous system.

Adult↗
PubMed1996

M6P/IGF2 receptor: a candidate breast tumor suppressor gene.

The mannose 6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2r) functions in the activation of TGFbeta, a potent growth inhibitor for most cell types, the degradation of the mitogen, IGF2, and the intracellular trafficking of lysosomal enzymes. We have found its expression to be significantly reduced in both rat and human hepatocellular carcinomas (HCCs) and recently reported loss of heterozygosity (LOH) at this locus with mutations in the remaining allele in human liver tumors. Using the polymerase chain reaction, we utilized two polymorphisms in the 3' untranslated region of M6P/IGF2r to screen breast tumors for LOH. Forty of 62 (65%) patients were informative (heterozygous) and 12/40 (30%) breast tumors had LOH; 5/19 (26%) carcinomas in situ (CIS) and 7/21 (33%) invasive carcinomas. To investigate the early molecular genetic events in breast carcinogenesis, we screened the CIS with LOH for mutations. In 2/5 (40%) of these tumors, missense mutations were found in the remaining allele that gave rise to significant amino acid substitutions. These findings provide evidence that M6P/IGF2r allelic loss is an early event in the etiology of breast cancer, that this gene functions as a tumor suppressor gene in the breast.

Amino Acid Sequence↗
PubMed1996

Prospective correlation of cervicovaginal cytologic and histologic specimens.

An effective, prospective, computer-guided method of correlation is reported. The mechanism for identification of cases, comparison of diagnoses, and reconciliation of discrepancies are explained. The results are similar to prior, retrospective, correlation studies. The benefits specific to this unique prospective approach include optimal capture of cases for correlation, minimization of errors before diagnoses are released to clinicians and patients, and internal standardization of diagnostic criteria. Three thousand four hundred and four consecutive paired cervicovaginal cytologies and biopsies were accessioned at the Pathology Department of Duke University Medical Center over a 43-month period. Of these, 481 paired cases (14%) had discordant diagnoses, defined as differing more than one degree of dysplasia or as dysplasia or carcinoma identified by only one modality. Additional evaluation reconciled the diagnostic differences in 35 cases. Eighteen initial diagnostic differences arose from cytologic screening errors, 16 from interpretive errors by staff pathologists, and one from superficial initial histologic sections. The remaining 446 discordances were attributed to sampling differences. The cytologic smear contained the diagnostic lesion in 40% of the cases and the biopsy the remainder, emphasizing the utility of pairing these sampling techniques in patients at risk for dysplasia.

Biopsy↗