Frozen section diagnosis of metastatic prostate adenocarcinoma in pelvic lymphadenectomy compared with nomogram prediction of metastasis.

OBJECTIVES: To compare the sensitivity and negative predictive values of frozen section analysis of pelvic lymphadenectomy in patients undergoing radical retropubic prostatectomy for prostate adenocarcinoma with the predictive power of published nomograms for metastasis to lymph nodes. METHODS: A retrospective review was performed on all patients who underwent bilateral pelvic lymphadenectomy and radical retropubic prostatectomy for prostate adenocarcinoma between 1991 and early 1997. The sensitivity and negative predictive values were computed comparing frozen section analysis, and patients were grouped by risk stratification. Comparison was made using the McNemar text. RESULTS: The sensitivity for detecting lymph node metastasis on frozen section analysis for all risk groups was 33% (9 of 27). The sensitivity for identifying patients at high risk of having nodal metastasis by published nomograms alone was 67% (18 of 27) (P = 0.04). The overall negative predictive value for frozen section analysis was 96.5% (503 of 521). The negative predictive value for uninvolved lymph nodes, using low and intermediate-risk groups stratified by published nomograms, was 97.9% (436 of 445). CONCLUSIONS: Frozen section analysis of pelvic lymph nodes to detect metastatic prostate adenocarcinoma is less sensitive in determining which patients will have lymph nodes involved by metastatic adenocarcinoma than using risk stratification by published nomograms. The negative predictive value of frozen section analysis in all risk groups was very high, up to 97.9%.

Effect of HER2/neu expression on survival in non-small-cell lung cancer.

Major prognostic factors for early-stage non-small-cell lung cancer (NSCLC) are tumor size and nodal status. It has been suggested that HER2/neu overexpression may be related to poor prognosis in NSCLC. We evaluated the significance of HER2/neu overexpression on survival in patients with NSCLC. Data were collected on 239 patients treated surgically for stage I/II NSCLC between 1987 and 1996. None of the patients received adjuvant chemotherapy or radiation. Formalin-fixed, paraffin-embedded tumor tissue samples were stained with p185/HER2 receptor antibody. Results were reported as positive (2+, 3+) or negative (0, 1+) (Group A). A separate analysis considered only 3+ as positive (Group B). HER2/neu overexpression was seen in 18% in Group A (43 of 239) and 6% in Group B (15 of 239). HER2/neu overexpression was highest in bronchoalveolar cell carcinoma and adenocarcinoma. More stage I tumors were positive than stage II in both groups, but this was significant only in Group A (21% vs. 7%, P = 0.02). No difference was seen with age, gender, or grade for either group. In Group A, the relapse rate was 55% for HER2/neu-overexpressing tumors and 31% for HER2/neu-negative tumors (P = 0.003). Median time to relapse in patients with HER2/neu-positive tumors was 2.9 years; it was not reached in patients with HER2/neu-negative tumors. Median survival of patients with HER2/neu-positive tumors was 3.6 years compared to 5 years in patients with HER2/neu-negative tumors (P = 0.66). In Group B, the relapse rate was 60% for HER2/neu-overexpressing tumors and 33% for negative tumors (P = 0.036). Median time to relapse was 3.4 years in HER2/neu positive and had not been reached in negative tumors. There was no difference in 5-year survival rates for both groups (47% for HER2/neu positive and 50% for negative, P = 0.66).

Estrogen and progesterone receptors in non-small cell lung cancer in 248 consecutive patients who underwent surgical resection.

CONTEXT: Different authors have reported estrogen receptor (ER) expression between 0% and 96.8% and progesterone receptor (PR) expression between 21.8% and 34.7%. OBJECTIVE: To examine the discrepancies in the literature regarding the expression of ERs and PRs in non-small cell lung cancer. DESIGN: Retrospective analysis. SETTING: A referral tertiary care center. PATIENTS: We reviewed 248 consecutive cases of stage I and II non-small cell lung cancers. METHODS AND RESULTS: Sections of formalin-fixed and paraffin-embedded tumor tissue were stained with ER and PR monoclonal antibodies using the avidin-biotin complex detection system with antigen retrieval. Men represented 66.1% of the patients, and women represented 33.9%. Large cell (undifferentiated) carcinoma constituted 10.4% of the entire population; squamous cell carcinoma, 39.1%; adenocarcinoma, 33.0%; and bronchoalveolar carcinoma, 17.3%. Patients with stage I disease represented 77.0% of the population. In this patient population, we found no nuclear or cytoplasmic expression of either ERs or PRs (95% confidence interval, 0%-1.2%). CONCLUSIONS: The absence of expression of ERs and PRs differs from previous articles, which use a variety of techniques, impairing a meaningful comparison of data. In addition, the presence of ER and PR expression in a lung carcinoma is supportive of a nonpulmonary primary tumor metastatic to the lung. The absence of their expression in non-small cell lung cancer does not support a role of these transcription factors in initiating and maintaining this neoplastic process.

Factors predicting the number of EUS-guided fine-needle passes for diagnosis of pancreatic malignancies.

BACKGROUND: The factors that affect the number of needle passes needed to diagnose pancreatic malignancies using endoscopic ultrasound (EUS) -guided fine-needle aspiration are unknown. METHODS: Patient and endosonographic data were prospectively recorded on 121 consecutive patients with pancreatic malignancy. Of these, 110 underwent EUS-guided fine-needle aspiration. A cytopathologist was in attendance for all aspiration procedures. RESULTS: Initial EUS detected a pancreatic mass in 96% of cases; 23% of these were not seen by computed tomography. EUS-guided fine-needle aspiration was performed in 109 of 110 (99%) patients, including 95 masses, 7 lymph nodes, and 7 hepatic metastases. EUS-guided fine-needle aspiration provided a cytologic diagnosis of malignancy in 104 of 110 (95%). Only tumor differentiation and the site of aspiration affected the number of passes. CONCLUSIONS: With the participation of a cytopathologist, EUS-guided fine-needle aspiration can diagnose pancreatic malignancies with a high degree of accuracy. Only the aspiration site (mass versus node/liver metastasis) can be used to direct the number of passes if a cytopathologist is not present. Without a cytopathologist in attendance, 5 to 6 passes should be made for pancreatic masses and 2 to 3 for liver metastases or lymph nodes; however, this approach will be associated with a 10% to 15% reduction in definitive cytologic diagnoses, extra procedure time, increased risk and additional needles.

Clinical utility of the alizarin red S stain on permanent preparations to detect calcium-containing compounds in synovial fluid.

The alizarin red S stain for permanent cytologic preparations is a valuable test that is complementary to compensated polarized light microscopic examination to detect calcium crystals. Alizarin red S has the greatest sensitivity for detection of calcium pyrophosphate crystals because crystals are stained regardless of how weakly or strongly birefringent they may be. Alizarin red S stain does not distinguish between amorphous types of calcium compounds; therefore, the different types of calcium compounds can be distinguished only when typical crystal morphologic features are present. Diagnostic importance can be attached to intracellular material that is stainable. In contrast, the diagnostic value of stainable, amorphous, extracellular material is unreliable because it is difficult to distinguish this extracellular material from contaminants frequently found in clinical specimens. Alizarin red S does not stain monosodium urate or corticosteroid crystals. Air-dried cytospin smears are helpful because they may frequently demonstrate more crystals than the wet-mount preparation. Furthermore, special stains can be performed subsequently on air-dried cytospin smears if necessary.

Permanent stained preparations of synovial fluid for detection of calcium compounds using alizarin red S.

Permanent preparations of air dried synovial fluids were prepared by staining calcium compounds with alizarin red S stain; each slide was coverslipped with Permount. Variables studied were: (a) concentration of the solution of alizarin red S, (b) pH of staining solution, (c) time of incubation in staining solution and aqueous and ethanolic content of staining solution. The staining effect of each solution was tested on calcium pyrophosphate dihydrate, calcium oxalate, apatite and monosodium urate (MSU). Of all the solutions, best results were obtained with 0.25% alizarin red S in 50% ethanol at pH 7.0 for 30 min. With this solution, the calcium-containing compounds were well stained. MSU did not stain and still preserved negative birefringence on polarization. Fixation of smears with ethanol served a double purpose: It fixed the slides without dissolving or removing MSU or the calcium compounds, yet it did dissolve five corticosteroids commonly used for intra-articular injection which may interfere with interpretation of compensated polarized light microscopy of synovial fluids.

Assessment of serum gamma glutamyl transpeptidase levels in low stage renal cell carcinoma.

In the past, serum levels of various enzymes have been studied to aid in the evaluation of neoplastic diseases. Gamma glutamyl transpeptidase (GGTP) is present in highest amounts in the proximal convoluted tubules of the kidney, which are considered to be the site of origin for renal cell carcinomas. A retrospective study of 63 patients who had serum GGTP levels tested within 10 days before the resection of a renal cell carcinoma was performed to determine whether serum GGTP was elevated in low stage (stages I and II) renal cell carcinomas. Only 5 of the 63 patients had elevated GGTP levels (two of which were only slightly elevated). The authors conclude that serum GGTP levels as routinely measured in clinical laboratories are not reliably elevated in low stage renal cell carcinomas.

Automated hematology: where we stand.

Rapid, accurate, and relevant laboratory testing is essential in an era of cost-effective medicine. The routine manual complete blood count (CBC) is a labor-intensive test that lacks reproducibility. The new automated instruments such as the Coulter S+ series offer "state of the art" precision and accuracy in counting more than 10,000 cells per blood sample. The nonoptical electronic impedance method yields RBC, WBC, and platelet data, as well as histograms that characterize hematologic data. Analysis of more than 3,500 cases yielded a false-negative rate of less than 4% and a false-positive rate of 30%, indicating the instrument's accuracy in recognizing and flagging abnormalities. All normal screened CBCs were free of significant abnormalities. The Coulter S+ series provides innovative parameters and histograms that aid in establishing differential diagnoses. We review the advantages and the limitations of automation. Morphologic examination of abnormal blood smears remains the cornerstone of diagnosis in both the new and the old hematology.

Fatal case of Epstein-Barr virus-induced lymphoproliferative disorder associated with a human immunodeficiency virus infection.

This is a case report of an Epstein-Barr virus-induced polyclonal lymphoproliferative disorder in a presumably immunocompromised patient with Western blot-confirmed antibodies to human immunodeficiency virus. Postmortem examination revealed a diffuse lymphoplasmacytic infiltrate with prominent numbers of immunoblasts involving multiple organs and resulting in multiple organ system failure.

Synthesis of brominated heptanones and bromoform by a bromoperoxidase of marine origin.

The presence of naturally occurring volatile halohydrocarbons in marine organisms, seawater, and the upper atmosphere has prompted a serach for their biosynthetic origin. An earlier report documented the preparation of an enzyme extract from a marine algae which catalyzed the formation of dibromomethane, tribromomethane, and 1-bromopentane from 3-oxooctanoic acid. This report did not establish a pathway nor did it examine potential intermediates involved in the synthesis of the halometabolites (Theiler, R., Cook, J., Hager, L., & Siuda, J. (1978) Science (Washington, D.C.) 202, 1094-1096). This paper shows that an extract of the green marine algae, Penicillus capitatus, which contains a potent bromoperoxidase activity, is capable of catalyzing the incorporation of bromide ion into organic combination in the presence of 3-oxooctanoic acid. By use of gas chromatography and mass spectroscopy, it has been possible to identify tribromomethane, 1-bromo-2-heptanone, 1,1-dibromo-2-heptanone, and 1,1,1-tribromo-2-heptanone as products of this reaction. The properties of the enzymatically synthesized products have been compared to authentic compounds and found to be identical. The mono- and dibromoheptanones can be utilized as precursors for the enzymatic formation of tribromoheptanone, but the final hydrolysis of the tribromoheptanone to bromoform appears to be a nonenzymatic reaction with the P. capitatus extracts.

Effect of anthraquinone dyes and evaluation of the kinetic mechanism of yeast phosphoglycerate kinase.

Cibacron Blue 3G-A (CB3G-A, I) was investigated as a ternary complex analogue of lactate dehydrogenase and phosphoglycerate kinase as had been suggested earlier (Stellwagen, E. (1977) Accts. Chem. Res. 10, 92-98). CB3G-A and Procion Brilliant Blue (PBB, II), a structural isomer of the Cibacron dye without the sulfonated benzoyl moiety, were attached covalently to Sepharose CL-6B. The two enzymes were adsorbed to the columns and then eluted by substrates in various combinations. CB3G-A and PBB interact similarly with the two enzymes in spite of the structural differences between the dyes indicating that the specific structure of CB3G-A is not a ternary complex analogue. Inhibition studies of phosphoglycerate kinase by CB3G-A suggest that 2 molecules of dye bind per monomer and are consistent with multiple substrate binding sites. It is suggested that the kinetic mechanism of phosphoglycerate kinase is best described as steady state random.