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V R Litle

Publications and source records attributed to V R Litle.

6 recordsLinked to original sources

Angiogenesis, proliferation, and apoptosis in anal high-grade squamous intraepithelial lesions.

PURPOSE: Management of anal high-grade squamous intraepithelial lesions is controversial. Anal and cervical high-grade squamous intraepithelial lesions are similar in that they occur in transitional squamous epithelium, are associated with human papilloma virus infection, and have increased incidence in the immunocompromised population. Ablation of cervical high-grade squamous intraepithelial lesions is preferred, but similar ablation or excision of anal high-grade squamous intraepithelial lesions may compromise bowel control; thus, there is a need to define the malignant potential of anal high-grade squamous intraepithelial lesions. METHODS: We analyzed 50 paraffin sections of normal anoderm, anal low-grade squamous intraepithelial lesions, high-grade squamous intraepithelial lesions, and anal squamous-cell carcinoma. Microvessels were detected immunohistochemically with von Willebrand factor and counted manually along the epithelial-stromal junction. Proliferation and apoptosis were determined in the epithelial cells with MIB-1 antibody immunostaining and the terminal deoxynucleotidyl transferase-mediated digoxigenin-11-dUTP nick end labeling, respectively. RESULTS: Microvascular density was significantly greater in anal high-grade squamous intraepithelial lesions (mean, 0.50 vessels/cm) vs. normal anoderm (mean, 0.21 vessels/cm; P = 0.0017, Mann-Whitney U test). The proliferative percentages were greater in low-grade squamous intraepithelial lesions, high-grade squamous intraepithelial lesions, and squamous-cell carcinoma (mean, 20.4, 21.8, and 23.6 percent) vs. normal anoderm (mean, 14.4 percent), although not significantly (P = 0.06, Kruskal-Wallis statistic). Although the mean proliferative proportions were similar in low-grade squamous intraepithelial lesions and high-grade squamous intraepithelial lesions, the apoptotic proportion was lower for high-grade squamous intraepithelial lesions than low-grade squamous intraepithelial lesions (10.13 vs. 19.96 percent, respectively; P = NS, Mann-Whitney U test). CONCLUSIONS: Angiogenesis, increased proliferation, and decreased apoptosis occur in anal high-grade squamous intraepithelial lesions as they do in the cervix before the development of malignancy. These biologic markers support the importance of anal high-grade squamous intraepithelial lesions as a potential premalignant lesion warranting surgical intervention.

Anal Canal↗

Molecular cytogenetic analysis of cytokeratin 20-labeled cells in primary tumors and bone marrow aspirates from colorectal carcinoma patients.

BACKGROUND: Low frequency epithelial cells in bone marrow from colorectal carcinoma patients are associated with an increased risk of recurrence and decreased survival. Current immunohistochemical approaches to detect epithelial cells in bone marrow aspirates rely on antibodies against cytokeratin 18 (CK18). The predictive value of CK18-based detection strategies is limited by false-positives that occur in approximately 30% of cases. Cross-reactivity of anti-CK18 antibodies with nontumor cells may contribute to the false-positive rate. Cytokeratin 20 (CK20) shows more restricted expression than CK18 and labels cells in colorectal tumors. METHODS: Immunofluorescence assays were used to quantify CK20-labeled cells in bone marrow aspirates and tumors from 18 Dukes stage C and D colorectal carcinoma patients to determine whether CK20 is useful in detecting micrometastases. Fluorescent in situ hybridization was used to determine whether CK-labeled subpopulations carried genomic aberrations associated with colorectal carcinoma. RESULTS: CK20-labeled cells occurred at frequencies approximately 5 x 10(-5) in control bone marrow aspirates from patients without colorectal carcinomas. Approximately 10(-4) CK20-labeled cells were present in 4 of 11 bone marrow aspirates (45%) from patients with Dukes stage D colon carcinoma. The mean frequency (5 x 10(-5) of CK20-labeled cells in Dukes stage C and D rectal carcinoma patients was statistically similar to control values. CONCLUSIONS. A subset of CK20-labeled cells in primary tumors and hepatic metastases are aneusomic. CK20-labeled cells in bone marrow aspirates are cytogenetically normal. These data demonstrate that CK20 cells in solid tumors may be cytogenetically aberrant, but suggest caution in the use of CK20 to detect micrometastases in bone marrow aspirates.

Adult↗

Genotype/phenotype analyses of low frequency tumor cells using computerize image microscopy.

Techniques to identify low frequency (i.e., 10(-4)-10(-5)) tumor cells in bone marrow and peripheral blood of cancer patients provide opportunities for early detection of disseminated disease and characterization of the properties of cells released from the tumor. Low frequency epithelial cells in marrow and blood can be detected using immunophenotypic markers directed against intracellular and/or cell surface antigens. However, nonspecific phenotypic labeling may compromise the ability to discriminate tumor from nontumor cells. We describe optimization of slide-based approaches that facilitate identification and subsequent molecular cytogenetic characterization of rare tumor cell populations in hematopoietic tissues. Colon tumor cells seeded in a hematopoietic background provided a model system to optimize methodologies that are applicable to detection and quantification of micrometastases in clinical specimens. Mixtures of cytogenetically aberrant epithelial cells and hematopoietic cells on slides were labeled with an anti-cytokeratin 20 (anti-CK20) antibody that recognizes > 90% of colon adenocarcinomas. Computerized image analysis was used to record the location of the immunofluorescent cells on microscopic slides. Cells on slides were then hybridized using fluorescence in situ hybridization (FISH) with repeat-sequence DNA probes to detect aneusomies. Previously discriminated epithelial cells were relocated for molecular cytogenetic characterization. Tumor cells present at frequencies approximating 5 x 10(-5) were discriminated on the basis of immunofluorescence and cell size. A low frequency (4 x 10(-4)) population of normal hematopoietic cells also labeled with anti-CK20 (data not shown). This strategy of sequential immunophenotyping and molecular cytogenetic analyses may be useful to discriminate tumor from nontumor cells in cancer patients with micrometastatic disease.

Genotype↗

Preoperative embolization of carotid body tumors: when is it appropriate?

To determine when to use preoperative embolization, we retrospectively reviewed a consecutive series of concurrently treated patients who underwent carotid body tumor resection between 1984 and 1994. Eleven nonembolized tumors (N-EMB group) and 11 embolized tumors (EMB group) were resected. The two groups were similar with respect to demographics and presentation, with the exception that more patients in the EMB group complained of painful neck masses. There was no significant difference in the pretreatment size of the neck mass between the two groups (N-EMB = 4.3 +/- 1.5 cm; N-EMB = 5.1 +/- 2.1 cm). Zero to 6 days after embolization, surgical resection was performed. There was no difference in the distribution of tumors, which were grouped according to Shamblin's classification, between the N-EMB and EMB patients. Two patients in each group required resection of the internal carotid artery, whereas a total of seven cranial nerves were resected. There were no differences in blood loss, number of blood transfusions, operative time, or perioperative morbidity between the N-EMB and EMB groups. Ten patients had new cranial nerve deficits and four of these patients required treatment for tenth nerve paralysis. Overall the total hospital stay was similar in the two groups, but the EMB group had a significantly longer preoperative stay compared to the N-EMB group (1.5 +/- 0.8 vs. 0.8 +/- 0.4 days; p = 0.02). These data show that preoperative embolization does not significantly improve outcome in patients undergoing resection of carotid body tumors measuring 4 to 5 cm. Therefore, in this era of costcontainment, preoperative embolization should not be used in the treatment of midsized carotid body tumors.

Adult↗

The continent ileostomy: long-term durability and patient satisfaction.

The long-term results of the continent ileostomy are controversial. Durability and patient satisfaction were evaluated by analyzing the outcome in 129 consecutive patients who had a continent ileostomy performed by one surgeon at the University of California, San Francisco, between 1975 and 1995. A quality-of-life questionnaire was sent to all patients for whom addresses were available (n = 121). Late outcome data could be obtained for 85 (66%) of the 129 patients. Three of the 85 patients died with their continent ileostomies but of unrelated causes. Fifty-one (60%) of 85 patients currently have the continent ileostomy (group A) (mean 15.1 years, range 2.7 to 21.7 years), whereas 31 (36%) of 85 have undergone conversion of continent ileostomy to conventional ileostomy (group B) (mean 5.4 years, range 0.2 to 20.4 years). Patients in group A underwent fewer major postoperative revisions (mean 0.7, range 0 to 4) than patients in group B (mean 1.3, range 0 to 8) (t test, P = 0. 088). The indications for pouch removal included valve dysfunction (42%), refractory pouchitis (23%), multiple fistulas (26%), Crohn's disease (6%), and other (16%) (four patients had two indications). Eighty-seven percent of survey respondents in group A considered their present state of health to be better than before their continent ileostomies. Fifty-seven percent and 82% of respondents in group A were not limited at all in regard to vigorous or moderate activity, respectively. Although in approximately one third of patients the pouch had to be removed, 97% of the remaining two thirds have a good to excellent outcome.

Adenomatous Polyposis Coli↗