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Biomedical subjects

M B Cohen

Publications and source records attributed to M B Cohen.

At least 91 records · Page 5Linked to original sources

Prognostic implications of extracapsular extension of lymph node metastases in prostate cancer.

We performed a retrospective review of surgical pathology specimens and clinical data for all patients with node-positive prostate cancer diagnosed in our institutions between 1985 and 1994. We used adjusted actuarial survival analyses and univariate and multivariate analyses to evaluate the clinical significance of extracapsular perinodal tumor extension. Sixty patients with histologically confirmed prostate cancer metastatic to regional lymph nodes were reviewed. Forty-two patients (70%) had evidence of extracapsular extension of the tumor into perinodal tissue. The 5-year adjusted cumulative survival rates for patients with extracapsular nodal extension was 54.6%, compared with 71.4% for patients with histologically confined nodal metastases (P < .05). Univariate and multivariate analyses revealed the presence of extracapsular nodal tumor extension to be an independent predictor of patient survival. In this study, only the histologic grade (Gleason score) of the primary tumor was a stronger predictive factor. These data suggest that histologic evidence of extracapsular tumor extension from lymph node metastases into perinodal tissue might be an important prognostic factor in patients with node-positive adenocarcinoma of the prostate. Development of a pathologic substage to include this feature might be warranted.

Adenocarcinoma↗

Soluble forms of CD44 and CD54 (ICAM-1) cellular adhesion molecules are released by human prostatic cancer cell lines.

We have identified that human prostatic cancer cell lines DU145, PC3, ND1, ALVA31 and JCA1 released soluble CD44 molecules and DU145, PC3 and ND1 released soluble CD54. Both soluble and surface CD44 were not found in LNCaP, and both forms of CD54 were not expressed in LNCaP and JCA1. CD54 was found to be highly expressed on cell surface in ALVA31, but these cells did not release soluble CD54. Expression of both cell surface and soluble forms were examined after treatment of cells with IFN-gamma, TGF-beta 1, or culturing in serum-free media. The concentration of soluble CD54 in supernatants changed to small extent after treatment with TGF-beta 1 and increased after treatment with IFN-gamma or in serum-free media. Cell surface expression of CD54 however, changed only minimally after treatment. The levels of cell surface and soluble CD44 also changed minimally after treatment with IFN-gamma and TGF-beta 1 but decreased in serum-free media and this was accompanied by marked elevation of soluble CD44 in supernatants. These data indicate that soluble CD44 might be released from cell surface by shedding whereas alternative splicing is the most likely mechanism of soluble CD54 release.

Cell Adhesion Molecules↗

Expression of CD44 isoforms in human prostate tumor cell lines.

We have examined the expression of the transmembrane glycoproteins CD44 in four human prostate tumor cell lines. Expression was examined at the protein level by flow cytometric analysis and Western blot, and at the mRNA level by reverse transcription-polymerase chain reaction (RT-PCR). All four cell lines (DU145, LNCaP, PC3, and ND1) expressed the standard CD44 isoform (CD44s) at the mRNA level and all cell lines except LNCaP expressed CD44s at the protein level. All four cell lines contained one or more isoforms containing the v6 region (exon 10) at the mRNA level, which has been associated with metastatic potential. However, a subpopulation of LNCaP and ND1 cells showed protein expression of v6. In addition, soluble CD44 isoforms were identified in cultured supernatants from all cell lines except LNCaP. These results show that CD44 isoforms are expressed on human prostate tumor cell lines, including the expression of variant isoforms containing the v6 region, and provide a rationale for the further study of this cellular adhesion molecule in prostate cancer. In addition, preliminary results indicate altered expression of CD44 in human prostatic adenocarcinomas examined immunohistochemically.

Animals↗

Utility of fine-needle aspiration biopsy in solid renal masses.

Renal fine-needle aspiration biopsy (FNAB) is used in several clinical scenarios: in patients with classic radiographic lesions; in non-operable patients with presumed high stage disease; and in patients with radiographic problematic lesions. Although overall, FNAB is a sensitive test, its role in the latter two populations has not been clearly established. To investigate the utility of FNAB in these patients, we retrospectively evaluated 43 renal FNABs in regards to diagnostic accuracy and clinical outcome. FNAB diagnoses were: malignant (36), suspicious (6), and insufficient (1). Our results indicate: 1) renal FNAB is accurate in patients with high stage lesions; 2) FNAB is less accurate in patients with radiographic problematic lesions; 3) the FNAB diagnosis of malignant increases the post-FNAB probability of malignancy, whereas the diagnosis of suspicious decreases the probability; and 4) there is excellent correlation for nuclear grade. We conclude that renal FNAB is useful in evaluating renal masses.

Adenocarcinoma↗

Cytologic features of villous adenoma of the ampullary region.

Villous adenoma of the ampulla of Vater is a rare but distinct pathologic entity. We studied seven brush cytology specimens from four patients with this unusual lesion all of whom had surgical pathologic confirmation and clinical follow-up. The distinguishing cytologic appearance includes the presence of slender, elongate columnar cells arranged singly or in small sheets and clusters. Long, thin, basally oriented nuclei occupy about one third of the cell and have fine, granular chromatin with one or more nucleoli. Although brushings of villous adenoma of the ampullary region may reveal a relatively benign but distinctive morphologic pattern, the aggressive nature of these lesions has been well documented, including those in our patients.

Adenoma, Villous↗

Infectious gastroenterocolitides in children: an update on emerging pathogens.

The recognition that bacterial infections induce signal transduction responses in infected epithelial cells also provides new avenues to consider as novel forms of therapy. For example, the chemokine interleukin-8, which attracts neutrophils to sites of mucosal infection, is produced by epithelial cells of gastric and intestinal origin in response to bacterial infection. Inhibitors of chemokine production or inhibition of the biologic effects of neutrophil chemoattractants have the potential to reduce both mucosal inflammatory responses and the attendant clinical sequelae. Eukaryotic cells also respond to infection with elevations in cytosolic second messengers, including inositol triphosphate (IP3) and calcium ([Ca2+]i). In intestinal epithelium, these second messengers can mediate the diarrheal response to infection. Calcium/calmodulin inhibitors may have a beneficial effect in treating those gastrointestinal infections mediated through changes in the level of cytosolic free calcium. DuPont and colleagues showed, for example, that oral therapy with zaldaride maleate relieves symptoms of disease and shortens the duration of diarrhea in travelers with ETEC-induced diarrhea. Evaluation of additional signal transduction responses to microbial infections should provide both new insights into the pathogenesis of gastrointestinal infectious diseases and novel approaches to consider for the prevention and therapy for these human illnesses.

Antidiarrheals↗

CD44 expression in benign and malignant nevomelanocytic lesions.

CD44 is an integral membrane glycoprotein that is a principal receptor for hyaluronan and plays a role in cell-extracellular matrix interactions. Recent studies of melanomas in mouse models have suggested that increased CD44 expression by these tumors may relate to metastatic potential. Immunohistochemical expression of CD44 (standard [s] and variant [v6]) in benign and malignant nevomelanocytic lesions was assessed in formalin-fixed, paraffin-embedded tissue and was correlated with histological parameters and prognostic factors. Cases included benign nevi (three junctional, four compound, five intradermal, five blue, six Spitz, one deep penetrating), architecturally disordered (dysplastic) nevi (three, and primary (22) and metastatic melanomas (eight). All of the benign lesions showed diffuse and essentially uniform membrane staining of CD44s in nevomelanocytic cells, regardless of lesion size, depth, or extent of dermal involvement. In contrast, semiquantitative analysis (0 to 3+) of the primary melanomas showed heterogeneous and decreased staining of CD44s, which inversely correlated with lesion size (-0.569) and depth of invasion (-0.622 and -0.617 for Breslow's depth and Clark's level, respectively). These results were significant at P < .05. CD44s expression in metastases paralleled that of their respective primaries. None of the benign nevomelanocytic lesions showed CD44v6 staining. In contrast, all of the malignant nevomelanocytic lesions showed cytoplasmic staining of the tumor cells. Pretreatment with chondroitinase did not alter CD44s staining. CD44s expression by immunohistochemical determination is uniform in benign nevomelanocytic lesions. Malignant melanomas show decreased, heterogeneous staining that inversely correlates with increasing size, depth, and level of invasion. CD44 expression may be a prognostic indicator in malignant melanomas. Tumor staining with anti-chondroitin sulfate monoclonal antibodies suggests that CD44s may be expressed as a chondroitin sulfate proteoglycan in primary melanomas.

Adult↗

The role of neovascularization in the survival of an arterialized venous flap.

This study compares survival of arterialized venous flaps placed on normal and impaired recipient beds in New Zealand White rabbit ear. Fasciocutanous flaps (4 x 5 cm) were perfused by an arteriovenous anastomosis; outflow was provided by one vein. In group 1, the arterialized venous flap was sutured into its bed on the ear; in group 2, a sheet of silicone was placed between the flap and the ear, providing an experimentally impaired recipient bed. Flap survival was expressed as a percentage of the total flap surface by means of a computerized image analysis system. Excellent survival (> or =95 percent) was noted in 16 of 21 arterialized venous flaps in group 1 versus 2 of 21 in group 2 (p < 0.01). Partial survival (50 to 94 percent) was observed in 2 of 21 arterialized venous flaps in group 1 and 15 of 21 in group 2. Poor survival (<50 percent) was noted in 3 of 21 in group 1 and in 4 of 21 in group 2. Microangiography was used to illustrate arteriovenous fistulas, the vascular network within the flaps, and neovessels in the periphery of the flaps. These data indicate that neovascularization is necessary for optimal survival of arterialized venous flaps in this experimental rabbit ear model.

Animals↗

Splenectomy complicating left nephrectomy.

PURPOSE: We attempted to clarify the details of incidental splenectomy complicating left nephrectomy. MATERIALS AND METHODS: We reviewed the literature and operations involving splenectomy performed during left nephrectomy between 1984 and 1994 at our university. Factors reviewed included patient characteristics, renal pathology, mechanisms of injury, blood transfusions and postoperative complications. RESULTS: Of the 418 left nephrectomies 18 (4.3%) resulted in splenectomy via a transperitoneal approach. Patients with a large or upper pole renal lesion, malignancy or advanced age are increasingly likely to undergo unanticipated splenectomy. CONCLUSIONS: Our results, combined with recommendations from the Centers for Disease Control and Prevention, suggest that all patients older than 65 years undergoing left transperitoneal nephrectomy or those at increased risk for splenic injury should receive preoperative pneumococcal vaccination.

Age Factors↗

Cytopathology and the pathology resident. A survey of residency program directors.

OBJECTIVE: To collect information on the status of cytopathology training in the United States. DESIGN: Questionnaire survey mailed in June 1994. SETTING: Pathology residency training programs in the United States. PARTICIPANTS: Pathology residency directors. MAIN OUTCOME MEASURES: Training length, numbers of cytology specimens, teaching methods and topics, and graduated responsibility. RESULTS: Of the 196 surveys mailed, 101 (52%) programs responded. The average length of required training was 3 months. The perceived optimal training time averaged 4.5 months, however, with 80% of programs requiring less than their stated optimum. The median numbers of gynecologic, nongynecologic, and fine-needle aspiration biopsy specimens examined per resident were 1100, 500, and 200, respectively. Cytopreparatory techniques, laboratory management, computer systems, and immunocytochemistry were included in over 75% of cytopathology training programs. Teaching at the microscope was rated as the most important teaching method by 90% of respondents. The majority of senior residents performed fine-needle aspiration biopsy procedures and screened and signed out cases with direct faculty supervision, but fewer than 20% of programs allowed senior residents to independently sign out specimens. CONCLUSIONS: Recommendations based on this review include a minimum training time of 3 months, improved training in both fine-needle aspiration biopsy techniques and gynecologic cytology, continuous exposure to cytopathologic techniques, and increased graded responsibility for senior residents.

Education, Medical, Graduate↗

Low-grade transitional cell carcinoma of the urinary bladder: application of select cytologic criteria to improve diagnostic accuracy [corrected].

The cytologic diagnosis of low-grade transitional cell carcinoma of the bladder is difficult, and the reported sensitivity of a positive diagnosis ranges from 0 to 73%. Using regression analysis, our laboratory previously reported the criteria of increased nuclear/cytoplasmic ratios, irregular nuclear membranes, and cytoplasmic homogeneity as indicative of low-grade transitional cell carcinoma. To examine the validity of these criteria, six observers examined 88 bladder-wash specimens (39 transitional cell carcinomas and 49 benign) and, using the selected criteria, graded each wash for the probability of malignancy. Diagnostic accuracy was measured using the receiver operating characteristic curve and the likelihood ratio. Overall observer accuracy was 76%, the sensitivity of a definitive negative diagnosis was 82%, and the specificity of a definitive positive diagnosis was 96%. We conclude that key cytologic criteria can be learned and effectively applied with high accuracy. Observer variation in diagnostic categories might reflect different confidence levels and probabilities of transitional cell carcinoma.

Carcinoma, Transitional Cell↗

Is microstaging of early invasive cancer of the urinary bladder possible or useful?

Reports suggest that it is possible and useful to classify T1 (Stage A) carcinomas of the urinary bladder into subgroups dependent on the depth of invasion as defined by the muscularis mucosae (MM). In an attempt to evaluate the reproducibility of these findings, we reviewed the slides from 77 cases of T1 bladder cancer diagnosed in 1983 in Iowa residents. The cases were identified through a statewide cancer registry. Slides and pathology reports were obtained from the original laboratories. Two pathologists independently evaluated each case, most (74 cases) of which were transurethral resections, for the presence or absence of MM and three levels of invasion (lamina propria, MM, and submucosa). Disagreements were resolved by simultaneous review resulting in a consensus diagnosis. Because of the population-based source, tissue had been obtained by multiple urologists and processed in multiple laboratories, resulting in noticeable variation in quality of material. Interobserver agreement for the level of invasion was poor between the two pathologists (kappa = 0.22; 95% C.I. = 0.08-0.36). Consensus resulted in 34 cases (44.2%) invasive to the lamina propria, 23 (29.9%) to the MM, and 11 (14.3%) to the submucosa. The level was indeterminate in nine (11.7%). All of the 77 cases were followed until death or 1993-95, with 57 patients dying during this interval. There were no significant differences in survival for each level of invasion (lamina propria, MM, submucosa) and the indeterminate cases, as determined by either consensus or individual observer evaluation. Our findings suggest that microstaging of early invasive bladder cancer is technically difficult and, at least in cases derived from various urologists and laboratories, does not yield a prognostically significant separation.

Humans↗

Fine-needle aspiration of the pancreas.

In patients with a palpable or radiographically identified pancreatic lesion, FNA is a safe and accurate procedure for procuring diagnostic tissue. Complications of the procedure are rare, and the morbidity and mortality are considerably less than that associated with open laparotomy and wedge biopsy. The most common complication associated with pancreatic FNA is acute pancreatitis. Contraindications to FNA include an uncorrectable bleeding diathesis, marked ascites, and suspected hydatid cyst. The accuracy of FNA for diagnosing pancreatic adenocarcinoma is about 80%, and the overall sensitivity can be increased by multiple needle passes. Close communication and collaboration among the clinician, radiologist, and pathologist can help assure that suitable tissue is obtained and maximize the diagnostic yield of the procedure. To this end, the presence of the pathologist or a cytotechnologist at the FNA procedure is desirable to assess the tissue as it is procured. The vast majority of malignant pancreatic neoplasms are ductal adenocarcinomas. Thus, the primary diagnostic problem facing the pathologist is differentiating adenocarcinoma from benign and/or inflammatory processes. The three key cytologic features that aid in this distinction are anisonucleosis, increased nuclear size, and nuclear molding. When all three of these features are present, the sensitivity of the procedure approaches 98%, and its specificity approaches 100%.

Biopsy, Needle↗