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Biomedical subjects

G B Schumann

Publications and source records attributed to G B Schumann.

At least 19 recordsLinked to original sources

A randomized controlled trial comparing intrathecal sustained-release cytarabine (DepoCyt) to intrathecal methotrexate in patients with neoplastic meningitis from solid tumors.

Standard treatment for neoplastic meningitis requires frequent intrathecal (IT) injections of chemotherapy and is only modestly effective. DepoCyt is a sustained-release formulation of cytarabine that maintains cytotoxic concentrations of the drug in the cerebrospinal fluid (CSF) for more than 14 days after a single 50-mg injection. We conducted a randomized, controlled trial of DepoCyt versus methotrexate in patients with solid tumor neoplastic meningitis. Sixty-one patients with histologically proven cancer and positive CSF cytologies were randomized to receive IT DepoCyt (31 patients) or IT methotrexate (30 patients). Patients received up to six 50-mg doses of DepoCyt or up to sixteen 10-mg doses of methotrexate over 3 months. Treatment arms were well balanced with respect to demographic and disease-related characteristics. Responses occurred in 26% of DepoCyt-treated and 20% of methotrexate-treated patients (P = 0.76). Median survival was 105 days in the DepoCyt arm and 78 days in the methotrexate arm (log-rank P = 0.15). The DepoCyt group experienced a greater median time to neurological progression (58 versus 30 days; log-rank P = 0.007) and longer neoplastic meningitis-specific survival (log-rank P = 0.074; median meningitis-specific survival, 343 versus 98 days). Factors predictive of longer progression-free survival included absence of visible central nervous system disease on neuroimaging studies (P<0.001), longer pretreatment duration of CSF disease (P<0.001), history of intraparenchymal tumor (P<0.001), and treatment with DepoCyt (P = 0.002). The frequency and grade of adverse events were comparable between treatment arms. In patients with solid tumor neoplastic meningitis, DepoCyt produced a response rate comparable to that of methotrexate and significantly increased the time to neurological progression while offering the benefit of a less demanding dose schedule.

Adult↗

Needle aspiration cytology of metastatic high-grade transitional-cell carcinomas of the urinary tract.

We reviewed 4 cases of high-grade transitional-cell carcinoma (TCC) of the urinary tract with solitary pulmonary metastases that were studied by transthoracic needle aspiration biopsy cytology. There were two grade II and two grade III TCCs. The two grade II tumors yielded, in needle aspirates, syncytial tumor-cell clusters showing ill-defined, granular cytoplasm and slightly pleomorphic nuclei with inconspicuous nucleoli. In one case the tumor-cell cluster showed a focal acinar arrangement, mimicking cells of an adenocarcinoma. In both cases the electron microscopy (EM) study of aspirated tumor cells revealed epithelial cells with well-formed cell junctions, intracytoplasmic vesicles, apical short microvilli, and focal interdigitation of lateral cell membranes, suggesting a urothelial neoplasm. The two grade III TCCs yielded, in needle aspirates, pleomorphic malignant cells singly and in small clusters, showing well-defined, granular cytoplasm and pleomorphic nuclei containing prominent nucleoli, suggesting a poorly differentiated adenocarcinoma or an anaplastic large-cell carcinoma. By EM examination the aspirated tumor cells from one case revealed well-formed cell junctions, intracytoplasmic vesicles, poorly formed microvilli, and focal interdigitation of lateral cell membranes, suggesting a urothelial differentiation. In the other case the tumor cells were pleomorphic cells with occasional cell junctions and no ultrastructural features as seen in the other 3 cases of TCC. The tumor cells from the two grade II TCCs showed strong immunopositive reaction with keratin 7 antibody and weakly positive reaction with carcinoembryonic antigen antibody (CEAA), while those of the two grade III TCCs displayed only a weak and focal immunopositive staining with keratin 7 antibody and strong reaction with CEAA.

Aged↗

Needle aspiration cytology of low-grade transitional cell carcinoma of the renal pelvis.

Five cases of histologically confirmed grade 1 papillary transitional cell carcinoma of the renal pelvis investigated by needle aspiration biopsy cytology were reviewed. In all cases the needle aspirates were hypercellular. Abundant benign-appearing urothelial cells in thick clusters, in small aggregates, and singly were seen in two cases. Numerous single and loosely aggregated urothelial cells with cytoplasmic extensions and slightly pleomorphic nuclei were noted in one case. In two patients numerous urothelial fragments of variable sizes showing defined cytoplasm and mildly nuclear pleomorphism were the main cellular findings.

Aged↗

Cytopathology of renal collecting duct carcinoma in urine sediment.

Two cases of histologically, immunohistochemically, and ultrastructurally confirmed collecting duct carcinoma of the kidney (CDCK) with positive urine cytology are reported. The patients' urine sediments showed malignant glandular cells in sheets with defined, variable, granular cytoplasm and oval, hyperchromatic nuclei containing micro- or macronucleoli. The cytologic differential diagnosis of CDCK is briefly discussed.

Adenocarcinoma, Papillary↗

Evaluation of asymptomatic microhematuria.

OBJECTIVES: The purpose of this study was to evaluate a comprehensive urine cytodiagnostic assay to assist in localizing the site of origin and the etiology of asymptomatic microhematuria. This analysis, which assesses various qualitative and quantitative aspects of the voided urine, is compared simultaneously with controls obtained from the established routine urologic evaluation. METHODS: One hundred consecutive subjects who presented solely for the evaluation of asymptomatic microhematuria were evaluated by the established routine urologic evaluation and a refined urine cytodiagnostic assay. For the purpose of this study, only calculi and neoplasms were considered significant findings. RESULTS: The incidence of significant urologic disease was 13% (3 renal neoplasms, 2 urothelial bladder carcinomas, and 8 urinary calculi). The refined urine cytodiagnostic assay identified both uroepithelial vesical neoplasms, 7 of the 8 urinary calculi, and none of the 3 renal neoplasms. The presence of dysmorphic urinary red blood cells (RBCs) and RBC casts was strongly suggestive of renal parenchymal bleeding. Overall, 43 of 44 subjects (98%) with dysmorphic RBCs and RBC casts failed to demonstrate any significant urologic etiology. CONCLUSIONS: These preliminary results suggest that the refined cytodiagnostic urine assay may be helpful in distinguishing whether a given patient's microhematuria is of a significant urologic or a renal parenchymal cause. The addition of this specialized urinalysis may prove a useful adjunct in improving the diagnostic yield in patients with asymptomatic microhematuria.

Adolescent↗

Intrathecal administration of interleukin-2 for meningeal carcinomatosis due to malignant melanoma: sequential evaluation of intracranial pressure, cerebrospinal fluid cytology, and cytokine induction.

A patient with interleukin (IL)-2 responsive metastatic melanoma developed meningeal carcinomatosis. Treatment was attempted with intrathecal (i.t.) IL-2 (5 weekly doses of 3-6 x 10(6) IU) without glucocorticosteroids. Marked increases in cerebrospinal fluid (CSF) pressure occurred 5-10 h following each IL-2 dose, resulting in reversible abnormalities of neurologic function. IL-2 clearance from the CSF ranged from 21 to 85 ml/h, with an apparent first order rate constant of 0.08-0.23 hr-1. These values were consistent with clearance by bulk flow mechanisms. Clearance also correlated directly with peak CSF pressure. Progressive increases in CSF tumor necrosis factor (TNF)-alpha and IL-6 levels, but not Il-1 alpha, were also noted over successive treatment cycles. Increasing neutrophilia (peaking at 12 h postdose) and a delayed lymphocytosis and monocytosis (at 20-30 h) were observed with each successive i.t. IL-2 dose. Activated lymphocytes were not observed in the CSF, however, suggesting that an exogenous source of activated lymphokine-activated killer (LAK) cells may be helpful in obtaining effective antitumor responses.

Adult↗

Analysis of cytodiagnostic urinalysis findings in 77 patients with concurrent renal biopsies.

We investigated the value of cytodiagnostic urinalysis in detecting and scoring the severity of the four types of renal lesions (glomerular, interstitial, tubular, and vascular). Both cytodiagnostic urinalysis and concurrent renal biopsy were performed in 77 patients (47 from native kidneys and 30 from transplants) and the scoring and findings assessed in a double-blinded fashion. Evaluation of the reproducibility for the counting of renal cells showed a low intraobserver and interobserver variation. Cytodiagnostic urinalysis correlated with the renal biopsy with respect to primary lesions in 42 (89%) of the native kidney cases, and in 23 (77%) of the transplant kidney cases. The accuracy of diagnosis of glomerular lesions in both native and transplanted kidneys was 0.91, and for acute rejection in transplanted kidneys, the accuracy of diagnosis was 0.73. Severity scores showed good correlation between cytodiagnostic urinalysis and renal biopsy in both transplanted and in native kidneys and cytodiagnostic urinalysis correlated well with the increase in creatinine levels. The most important components of cytodiagnostic urinalysis for the diagnosis of glomerular lesions were dysmorphic erythrocytes and proteinuria. The specificity and sensitivity of dysmorphic erythrocytes for a glomerular lesion were 0.89 and 0.88, respectively. In cases with biopsy-proven glomerular lesions, more severe changes were found by cytodiagnostic urinalysis when the biopsy showed proliferative lesions in the glomeruli than when normal glomeruli were found by light microscopy. Cytodiagnostic urinalysis has the advantage over renal biopsy that it can be repeated as often as necessary and thus allows observation of the development or regression of the renal lesion over time. We conclude that cytodiagnostic urinalysis is well correlated with the renal biopsy and that it provides valuable and quantitative information regarding the disease process in the kidney.

Adult↗

Primary urinary cytodiagnosis of a bladder small-cell carcinoma.

A small-cell undifferentiated tumor of the bladder in a 69-yr-old man with asymptomatic hematuria is described. Urine cytology showed abundant, small, round-to-oval hyperchromatic cells with coarse chromatin, nuclear molding, and high nuclear/cytoplasmic ratios. A primary cytodiagnosis of small-cell undifferentiated cancer with associated severe urothelial atypia was made. Immunohistochemical stains were negative for neuron-specific enolase, leukocyte common antigen, chromogranin, epithelial membrane antigen, prostatic acid phosphatase, and prostate-specific phosphatase. The diagnosis was confirmed histologically by studies performed on cystoscopic bladder biopsy material.

Aged↗

Diagnosis of cytomegalovirus pneumonitis on bronchoalveolar lavage fluid: comparison of cytology, immunofluorescence, and in situ hybridization with viral isolation.

Forty-three bronchoalveolar lavage (BAL) specimens from 40 immunocompromised patients were studied for the presence of cytomegalovirus (CMV) by rapid diagnostic methods. DNA in situ hybridization, cytology, and immunofluorescence were compared to conventional cell culture. Eleven (25%) of the 43 BAL samples grew CMV in culture. In situ hybridization detected 6 of these 11 for sensitivity, specificity, and predictive values of positive and negative of 55%, 94%, 75%, and 86%, respectively. Cytology had a sensitivity of 73% and specificity of 100%. Six Papanicolaou-stained cytospins were screened cytologically versus one hybridization cytospin, and the higher sensitivity of cytology may reflect this extensive sampling. The immunofluorescent method had a sensitivity equal to that of cytology (73%): however, the specificity (72%) was significantly less than that of either the probe or cytology. These data suggest that although in situ hybridization can be a rapid, useful method for detecting CMV in BAL specimens, cytology appears to be a more sensitive method.

Bronchoalveolar Lavage Fluid↗

Quantitative analysis of sputum cytologic differences between smokers and nonsmokers.

An exploratory analysis of sputum cytology was conducted to determine the extent and nature of cytomorphologic differences between smokers and nonsmokers. Specifically, alveolar macrophages, pigmentation of macrophages, neutrophils, mucus, mucous spirals, columnar cells, metaplastic cells, and dysplastic cells were analyzed and compared in 349 smokers and 93 nonsmokers. Results indicate that smokers have significantly higher scores on all components than do nonsmokers. Pigmentation of macrophages, alveolar macrophages, and mucous spirals were the major components discriminating between smokers and nonsmokers. A comparison of the nonsmoking sample with a different group of smokers (n = 466) revealed similar findings. Using the cytomorphologic parameters as the basis for classification, discriminant function analysis was able to classify correctly 94 percent of the nonsmokers and 91% of the smokers, a finding confirmed in the second group of smokers. These data indicate that smokers differ reliably from nonsmokers with respect to their cytomorphologic profile.

Adult↗

Cytologic identification of clinically occult proliferative breast disease in women with a family history of breast cancer.

A cytologic method for sampling the normal breast by fine-needle aspiration (FNA) was used to determine the frequency of clinically inapparent proliferative breast disease (PBD) in women with family histories of breast cancer. The authors attempted to obtain specimens from each quadrant of both breasts in 51 female first-degree relatives of breast cancer patients. The study group had no detectable masses by physical examination or mammography. Samples were prepared on membrane filters, Papanicolaou stained, and evaluated cytomorphologically. Three hundred seventy-eight of 408 (92.6%) possible quadrants were sampled; cellular material was obtained from 290 (76.7%) quadrants. PBD was identified in 20 of the 51 women (39.2%). When epithelium was obtained, nuclear area, perimeter, and diameter were measured with the use of computerized image analysis. Nuclei in samples containing atypical hyperplasia showed significant differences in these parameters when compared with cells from samples containing normal epithelium or benign hyperplasia. The authors' findings indicate that FNA sampling and computerized image analysis are useful in the detection and characterization of clinically inapparent PBD.

Adipose Tissue↗

Comparison of Papanicolaou's stain with the Gomori methenamine silver (GMS) stain for the cytodiagnosis of Pneumocystis carinii in bronchoalveolar lavage (BAL) fluid.

The cytodiagnosis of Pneumocystis carinii (PC) in bronchoalveolar lavage (BAL) fluids has traditionally required a special stain such as Gomori's methenamine silver (GMS) stain. Recent reports indicate that identification of foamy alveolar casts (FACs) with Papanicolaou's (Pap) stain may provide a sensitive and less complicated way of making the diagnosis. To confirm these observations, results on a series of 318 BALs were reviewed. PC was identified on 65 (20%) specimens from 54 patients. Pap stains and GMS stains were positive on 56 (86%) of these BALs. Pap stains were positive on seven (11%) specimens that had negative GMS stains. PC was later confirmed on these specimens by other methods. Only two (3%) BALs had positive GMS stains and negative Pap stains. The results of this study confirm other reports that show that PC can be sensitively diagnosed with the Pap stain. The authors suggest that routine special stains for PC are unnecessary on BALs.

Bronchoalveolar Lavage Fluid↗

Inheritance of proliferative breast disease in breast cancer kindreds.

Previous studies have emphasized that genetic susceptibility to breast cancer is rare and is expressed primarily as premenopausal breast cancer, bilateral breast cancer, or both. Proliferative breast disease (PBD) is a significant risk factor for the development of breast cancer and appears to be a precursor lesion. PBD and breast cancer were studied in 103 women from 20 kindreds that were selected for the presence of two first degree relatives with breast cancer and in 31 control women. Physical examination, screening mammography, and four-quadrant fine-needle breast aspirates were performed. Cytologic analysis of breast aspirates revealed PBD in 35% of clinically normal female first degree relatives of breast cancer cases and in 13% of controls. Genetic analysis suggests that genetic susceptibility causes both PBD and breast cancer in these kindreds. This study supports the hypothesis that this susceptibility is responsible for a considerable portion of breast cancer, including unilateral and postmenopausal breast cancer.

Adult↗

Chain of events in Papanicolaou smear testing: impact on quality assurance.

Quality assurance is defined in this article as a comprehensive program aimed at preventing and controlling errors from the time a test is ordered until test results are reported and utilized in the care of the patient. Quality control is only one facet of a total quality assurance program. Recently, the general public, professional organizations, and regulatory agencies have scrutinized the standards and practice of Papanicolaou smear testing. The components of quality assurance for gynecologic cytology are reviewed, and the chain of events in performing effective cytologic testing is described. The impact of various events on the outcome of Papanicolaou smear testing is thoroughly discussed.

Cytological Techniques↗

Quantitative sputum cytologic findings in 109 nonsmokers.

While sputum cytologic findings associated with cigarette smoking have been described, little information is available regarding nonsmokers for comparative analysis. Over a 3-month period, our cytopathology laboratory examined 3-day pooled sputa from 109 never smokers. Eighty-five percent were able to produce satisfactory results without recourse to induction. Ninety of 93 (97%) individuals had negative or reactive sputum cytologic findings. No carcinoma was identified. Two cases showed metaplastic changes and one case revealed dysplasia but all were from symptomatic never smokers. Eight components of stimulation of bronchial epithelium were microscopically quantified on each case and the mean values of each were calculated to produce a profile of an asymptomatic never smoker.

Adult↗

Clinical utility of head and neck aspiration cytology.

Over the past 3.5 yr, we have examined 195 head and neck fine-needle aspiration (FNA) specimens from three diverse medical settings. Specimens were collected in saline solution or Saccomanno fixative and processed using cytocentrifugation or membrane filtration. This allowed us simultaneously to perform cytologic evaluations, special stains, and immunologic marker studies from a single specimen. Good correlation between clinical experience with FNA and obtaining satisfactory specimens was demonstrated. Our sensitivity (89%) and specificity (94%) reflect problems associated with specimen collection in a training environment where clinician experience with the procedure is low. A definitive diagnosis was possible in most cases, and the treatment plan was often based on the FNA results. In patients without a history of a primary malignancy, a FNA done early in the clinical course helped direct the initial workup of the patient, saving time and expense.

Adolescent↗