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R L Katz

Publications and source records attributed to R L Katz.

At least 19 recordsLinked to original sources
PubMed1996

Image analysis of cellular DNA content in peritoneal fluid of patients with ovarian tumors of low malignant potential and invasive epithelial ovarian cancer.

Image analysis has rarely been used to quantitate the DNA content of intact cells derived from peritoneal fluid in patients with ovarian malignancy. An average of 118 (range 100-208) of the most atypical, visually selected Feulgen-stained cells in peritoneal fluid obtained from 46 patients undergoing primary cytoreductive surgery for histologically proven ovarian tumors of low malignant potential and truly invasive ovarian cancer were evaluated retrospectively using the SAMBA-4000 Image analysis system. The patients were stratified into 3 groups: 16 with ovarian tumors of low malignant potential (LMP), 14 with low-stage disease (LSD) (FIGO I and II), and 16 with advanced-stage (ASD) (FIGO III and IV). A pattern of high-degree aneuploidy with negative balance (means: LMP, 3.3; LSD, 20.5; ASD, 32.0), increased proliferative index (LMP, 11.2; LSD, 16.1; ASD, 13.9), and percentage of cells with DNA content greater than 5C (LMP, 6.7; LSD, 6.5; ASD, 9.5) was demonstrated in the peritoneal fluid of 8 of 16 patients with LMP (50%), 8 of 14 patients with LSD (57%), and 13 of 16 with ASD (81%). The median disease-free interval for patients with invasive epithelial ovarian cancer with peritoneal DNA diploid tumor cells was 57 months and for those with DNA aneuploid tumor cells 28 months, while in patients with LMP it was 65 and 54 months, respectively. In total, 19 patients developed a recurrence (LMP, 2; LSD, 5; ASD, 12) of which 17 were shown to have DNA aneuploid cells in the peritoneal fluid. Multivariate analysis, however, did not identify aneuploid population in the fluid, ploidy balance, proliferation indices, or degree of hyperploidy as an independently significant variable for predicting recurrence. It did appear, however, that tumor cells in peritoneal fluid with a degree of hyperploidy greater than 8 had a strong correlation for development of recurrence, although not statistically significant. Interactive image analysis of tumor cells in peritoneal fluid proved to be a valuable adjunct to cytodiagnosis. Seven of 28 patients (25%) who were underdiagnosed by cytology alone (LMP, 2; LSD, 3; ASD, 2) were shown to have malignant cells in their peritoneal fluid, while 2 of 18 patients (11%) who were called positive by cytology (LMP, 1; LSD, 1) showed diploid pattern histograms and upon review were interpreted as reactive mesothelial cells.

Adult↗
PubMed1996

Molecular diagnosis of exocrine pancreatic cancer using a percutaneous technique.

BACKGROUND: The K-ras oncogene is activated by point mutations at codon 12 in most patients with exocrine pancreatic cancer. Mutant-enriched polymerase chain reaction (PCR) amplification can enhance the detection of mutated K-ras. This technique was applied to patients undergoing percutaneous fine-needle aspiration (FNA) biopsy of suspect pancreatic lesions. METHODS: Twenty-five patients underwent percutaneous FNA of the pancreas for cytologic and molecular analysis. After preparing cytologic smears, the 22-gauge needle and syringe used for FNA were rinsed in RPMI-1640. The specimen was centrifuged, and DNA was extracted from the supernatant and subjected to mutant-enriched PCR using appropriate mismatched primers that introduce a BstNI restriction endonuclease clevage site at codon 12 of wild-type, but not mutant, K-ras. After digestion with BstNI, the DNA was reamplified. To increase assay sensitivity, the final five PCR cycles were completed incorporating 5 microCi of (alpha-32P)dCTP. The DNA was then redigested and subjected to gel electrophoresis and autoradiography. RESULTS: The median amount of DNA retrieved per specimen was 3.33 micrograms. Mutant K-ras was detected as a band of 143 bps; residual wild-type DNA was seen as a 114-bp fragment. Twenty-one of 25 specimens demonstrated mutated K-ras DNA. Two patients with nondiagnostic cytology results had mutated K-ras DNA; adenocarcinoma of pancreatic origin was confirmed in both cases after pancreatectomy. CONCLUSION: The molecular diagnosis of pancreatic cancer through identifications of mutations in K-ras can be readily performed on specimens obtained by percutaneous FNA. As aggressive multimodality management of this disease becomes more common, pretreatment analysis of molecular determinants may have greater clinical significance.

Adenocarcinoma↗
PubMed1996

DNA image analysis of urinary cytology: prediction of recurrent transitional cell carcinoma.

To evaluate the utility of image analysis in monitoring patients with transitional cell carcinoma, we studied, by cytologic means and by image analysis, 78 urinary tract specimens from 66 patients, of whom 49 (74%) had a previous history of transitional cell carcinoma. The specimens consisted of 51 (65%) voided urine specimens, 12 (15%) bladder washings, 8 (10%) ureteral washings, 3 (4%) ureteral brushings, 2 (3%) renal pelvic washings, and 2 (3%) catheterized urine specimens. DNA histograms were classified into five patterns on the basis of their DNA index and the percentage of their cells with DNA content greater than 5c: diploid (single peak in the 2c region with no cells greater than 5c), intermediate (diploid with less than 10% of cells greater than 5c), aneuploid (single peak or multiple peaks between the 2c and 4c region or more than 10% of cells greater than 5c), tetraploid (at least 10% of cells in the 4c region and a corresponding peak at 8c), and polyploid (multiple peaks in the 2c, 4c, 8c, and 10c regions). Of the 78 cases, 22 were diploid, 24 were intermediate, 29 were aneuploid, one was tetraploid, and two were polyploid. Histologic confirmation or clinical follow-up was found in 29 aneuploid cases, 13 intermediate cases, and one diploid case. Most cases of carcinoma in situ (five of six) and invasive tumors (12 of 17) were aneuploid. The sensitivity was 100%, and the specificity was 73% when cytologic and image analysis results were combined. We conclude that image analysis, when combined with cytologic examination, is a reliable noninvasive diagnostic test for monitoring patients with transitional cell carcinoma; aneuploidy is specific for malignancy; and the presence of cells greater than 5c, although frequently associated with tumor recurrence, can be seen in non-neoplastic conditions.

Adult↗
PubMed1995

Enhanced TAG-72 expression and tumor uptake of radiolabeled monoclonal antibody CC49 in metastatic breast cancer patients following alpha-interferon treatment.

The IFNs, alpha and gamma, have been shown to enhance the tumor-associated glycoprotein (TAG-72) on adenocarcinoma cells in vitro and in mice with human breast cancer xenografts, resulting in improved targeting of monoclonal antibody CC49. To determine the effect of IFN-alpha on biodistribution and tumor uptake of 131I-labeled CC49, patients with metastatic breast cancer were randomized to either receive or not receive IFN-alpha (3 million units daily for 14 days) by s.c. injection. Three days after beginning IFN-alpha, all patients received 10-20 mCi of 131I-CC49 (specific activity, 16.7 mCi/mg) i.v. Total-body Anger camera scans, along with total-body blood and plasma pharmacokinetics, were performed. Tumor biopsies were taken in all patients before and 48 h after IFN-alpha treatment. There were no significant differences in number of metastases imaged or whole-body, blood and plasma pharmacokinetics between IFN-alpha-treated and untreated patients. Quantitative immunohistochemistry on biopsy specimens from IFN-alpha-treated patients demonstrated a significant increase in mean +/- SEM TAG-72 expression (45.7 +/- 19.4%) compared to patients that were not given IFN-alpha (1.3 +/- 0.95%; P < 0.05). Although slight increases in the percent injected dose of 131I-CC49 in tumor occurred after IFN-alpha-treatment, the changes were not significant at the P < 0.05 level. These data suggest that IFN-alpha may be useful in enhancing TAG-72 antigen expression in vivo in humans, despite modest improvement in tumor uptake of CC49, possibly because of limited tumor access or other unknown factors.

Adenocarcinoma↗
PubMed1995

Cytologic findings of collecting duct carcinoma of the kidney.

We report the cytologic features of eight fine-needle aspirations (FNA) and eight exfoliative specimens of collecting duct carcinoma (CDC) obtained from six patients. The four men and two women ranged in age from 27 to 69 years (mean = 45 yr) and all had advanced stage disease at presentation (one stage III, five stage IV). Five of the six patients died of widespread disease, and one is alive and well (mean survival, 28 mo; range, 11-48 mo). The smears of the FNA and exfoliative specimens were scantly to moderately cellular. Tumor cells showed moderate pleomorphism and were arranged primarily in cohesive groups that rarely had a papillary configuration. Nuclei had irregular nuclear contours, coarse chromatin, and one to three nucleoli. In the majority of cases the cytoplasm was finely vacuolated, and occasionally there were large intracytoplasmic vacuoles. Intracytoplasmic mucin was demonstrated in two aspirates. Psammoma bodies were present in four of the seven fluids. In two patients, the cytologic diagnosis was supported by positive immunostaining for high-molecular-weight keratin and Ulex europaeus agglutinin I lectin. Leu M-1 was focally positive in one case and negative in the other. The cytologic features of CDC were readily identified as malignant; however, they were not distinctive and overlapped with those of high-grade renal cell carcinoma with papillary features and transitional cell carcinoma.

Adult↗
PubMed1995

Significance of peritoneal cytology in patients with potentially resectable adenocarcinoma of the pancreatic head.

BACKGROUND: Recurrence in the peritoneum occurs in up to 50% of patients after a potentially curative pancreaticoduodenectomy. Previous authors have implicated preoperative fine-needle aspiration (FNA) as a cause of intraperitoneal tumor dissemination, although prior studies of peritoneal cytology findings have largely involved patients with locally advanced disease. METHODS: A consecutive series of patients referred to our institution between 1991 and 1993 with suspected or biopsy-proven adenocarcinoma of the pancreatic head was studied prospectively. All patients fulfilled criteria for resectability as assessed by computed tomography: no metastatic disease, no encasement of the superior mesenteric or hepatic arteries, and a patent superior mesenteric-portal venous confluence. Peritoneal washings were obtained at the time of staging laparoscopy and/or at subsequent laparotomy. Data regarding peritoneal cytology results, previous FNA, preoperative chemoradiation, eventual resection, pattern of disease recurrence, and survival were collected. RESULTS: A total of 80 peritoneal washings from 60 consecutive patients were prospectively examined. Forty-nine (82%) of 60 patients underwent FNA before peritoneal washings were obtained. A total of four patients (7%) had positive peritoneal cytology findings: three (6%) of 49 who underwent prior FNA and one (9%) of 11 with no prior FNA. Similarly, no differences in eventual peritoneal failure or short-term survival were observed for patients who underwent prior FNA compared with patients who did not. All four patients with positive peritoneal cytology findings had metastatic disease (liver, three; peritoneum, one) at a median of 4.8 months after diagnosis; three of the four died of disease at a median of 8 months. CONCLUSIONS: Positive peritoneal cytology findings are rare in patients with radiologically resectable adenocarcinoma of the pancreas. When found, positive peritoneal washings are an indicator of advanced disease characterized by unresectability, early metastasis, and short survival. Computed tomographic-guided FNA does not appear to increase the risk for positive peritoneal washings and represents a valid approach to the pretreatment diagnosis of patients with suspected pancreatic malignancy.

Adenocarcinoma↗
PubMed1995

Relationship between DNA ploidy level, nuclear size, and survival in large cell lymphoma.

Intermediate and high grade subtypes of non-Hodgkin's large cell (LCL) and immunoblastic lymphomas exhibit considerable variability, and histologic morphology alone may not adequately characterize those features important for prognosis. The relationship between nuclear morphology and survival was assessed in a series of 50 cases of large cell lymphomas in which ploidy, proliferation, and nuclear area (NA) were measured. Ploidy was calculated by both DNA index (DI) and DNA histogram type (DHT). Proliferation was calculated from the proportion of S phase (SPF) cells present in the DHT. These four parameters were measured using image cytometry of Feulgen-stained nuclei from fine-needle aspirations. To characterize the relationship with survival, these parameters were associated with the clinical follow-up of the patients. The results show that of the 50 LCL cases, only 5 were clearly aneuploid, whereas the remaining 45 were either diploid (29 cases), tetraploid/hypotetraploid (13 cases), or weakly aneuploid (hyperdiploid, 3 cases). Of the 34 patients who died from their disease, both smaller NA and DI correlated with longer survival in an equivalent fashion; neither conferred greater sensitivity when combined with the other. The SPF did not correlate with survival. In LCL, aneuploidy seems to be a relatively uncommon event, but when present ploidy measurement appears useful to define prognosis.

Adult↗
PubMed1995

Image analysis--derived morphometric differences in fine needle aspirates of ductal and lobular breast carcinoma.

The differentiation of ductal and lobular carcinoma (including lobular carcinoma in situ) of the breast has important prognostic implications; thus, preoperative differentiation of these entities via fine needle aspiration could have a substantial impact on the therapeutic options offered to patients. However, well-defined, reliable light microscopic criteria do not currently exist for their distinction in cytologic preparations, particularly when the differential diagnosis of lobular versus low nuclear grade ductal carcinoma is considered. In this study we utilized a morphometric image analysis system to identify distinct nuclear features useful in the differentiation of these two entities and found that a number of significant differences do exist. Although some features (i.e., nuclear size) may be detected in traditional cytologic preparations, others may not be detected by the human observer, supporting a role for automated morphometric analysis as a useful adjunct in the distinction of lobular and low nuclear grade ductal carcinoma in fine needle aspirates of the breast.

Biopsy, Needle↗
PubMed1994

Correlation of two AgNOR counts with Ki-67 labeling index: a study in fine-needle aspirates of lymphoproliferative disorders and breast carcinoma.

The Ki-67 antibody binds to nonresting cells where Ki-67 labeling index (KLI) reflects proliferative activity (PA). The argyrophilic nucleolar organizer regions (AgNOR) counts have been correlated to ploidy and/or PA. Two AgNOR counting methods distinguish ploidy from PA. The first count is the mean AgNOR count (mAg-NOR) which correlates with ploidy. The second is the percentage of nuclei with > or = 5 AgNORs/nucleus (pAgNOR) which reflects PA. To explore this relationship, we separately stained smears of 20 fine-needle aspirates (FNAs) of lymphoproliferative disorders (n = 12) and breast carcinomas (n = 8) for AgNOR and Ki-67. We also double-stained 10 of the smears for both AgNOR and Ki-67. The correlation of pAgNOR counts and KLI was statistically significant (P < 0.0001) whereas it was not between mAgNOR and KLI (P = 0.13). Additionally, using the double stain, the Ki-67 negative cells had an AgNOR granule range of 1-3/nucleus with a mean of 1.33 (+1.86 SD). The Ki-67 positive cells showed an AgNOR granule range of 2-12/nucleus with a mean of 4.15 (+/- 1.02 SD) (P < 0.0002). We thus conclude that pAgNOR is a more reliable indicator of PA than mAgNOR and that four AgNORs/nucleus is an acceptable number differentiating proliferating from resting cells.

Biopsy, Needle↗
PubMed1994

Fine-needle aspiration of pancreatic extramedullary plasmacytoma: possible confusion with islet cell tumor.

We report two cases of extramedullary plasmacytoma (EMP) of the pancreas, diagnosed by fine-needle aspiration (FNA). Plasmacytoma of the pancreas is a rare neoplasm with only 12 cases recorded in the literature. Because of its scarcity and the cytomorphologic similarity between plasma cells and endocrine cells, EMP of the pancreas may be confused with neuroendocrine (islet cell) tumors of the pancreas. Immunohistochemical staining for light chain and/or neuroendocrine markers will prevent diagnostic error when interpreting plasmacytoid neoplasms of any site susceptible to endocrine tumors, including the pancreas.

Adenoma, Islet Cell↗
PubMed1994

Fine-needle aspiration cytology of recurrent and metastatic mixed mesodermal tumors.

We report the cytological and clinical findings of 16 fine-needle aspirates (FNAs) performed on recurrent (n = 6) and metastatic (n = 10) mixed mesodermal tumors (MMMTs). The median interval between the primary diagnosis and FNA was 16 mo. Primary sites were the endometrium (n = 11), the ovary (n = 3), the cervix (n = 1), and pelvic soft tissue (n = 1). Primary tumors showed carcinoma with homologous mesenchymal components in 13 cases and focal heterologous elements in three (two chondrosarcomas and one rhabdomyosarcoma). The FNAs showed carcinoma in all 16 cases, with adenocarcinoma differentiation in three. Mesenchymal elements were identified in aspirates of three recurrent and two metastatic lesions. They were all homologous. aspirates. We conclude that mesenchymal components in FNAs of MMMTs are less likely to be seen in metastatic lesions, and that heterologous mesenchymal components are rarely seen in these aspirates even in recurrent disease. These findings confirm that the epithelial component is responsible for the malignant behaviour of MMMTs, and suggest that these lesions may need to be classified as sarcomatoid carcinomas rather than true carcinosarcomas.

Adenocarcinoma↗
PubMed1994

Immunotyping of lymphoma by fine-needle aspiration. A comparative study of cytospin preparations and flow cytometry.

Immunotyping is an essential adjunct to cytomorphology for the diagnosis of lymphoma by fine-needle aspiration (FNA). Two independent techniques, cytospin preparations and flow cytometry, were used for immunotyping studies on 71 patients with histologically confirmed non-Hodgkin's lymphoma (63 B-cell lymphomas and 8 T-cell lymphomas). Diagnostic concordance between the two methods was obtained in 69 patients (97%). kappa, lambda, and CD3 (Leu-4) markers were routinely measured on all cytospins, and additional markers were requested when indicated. The standard panel measured by flow cytometry included 14 markers. In general, mean values of light-chain (kappa and lambda) immunoglobulins were consistently slightly higher by cytospin analysis than by flow cytometry. Light-chain immunoglobulin ratios (kappa/lambda or lambda/kappa) obtained by both methods proved to be reliable independent predictors of polyclonality or monoclonality. Correlation studies using the Spearman rank coefficient revealed good concordance among values of kappa, alpha, CD3, and CD5 obtained by the two techniques, suggesting that subjective quantitation by cytospins yields similar results to objective quantitation by flow cytometry. Cytospin analysis and flow cytometry appear equally capable of immunotyping aspirated lymphoid samples reliably. The advantages of each method are discussed.

Biopsy, Needle↗
PubMed1994

Intraperitoneal adoptive immunotherapy of ovarian carcinoma with tumor-infiltrating lymphocytes and low-dose recombinant interleukin-2: a pilot trial.

A pilot study was conducted in patients who had advanced epithelial ovarian carcinoma, and who were refractory to platinum-based chemotherapy, to determine the feasibility and clinical effects of a schedule of intraperitoneal (IP) tumor-infiltrating lymphocytes (TIL) expanded in recombinant interleukin-2 (rIL-2), and low-dose rIL-2 IP. TIL were expanded from solid metastases or malignant effusions in serum-free AIM V medium supplemented with low concentrations (600 IU/ml) or rIL-2 using a four-step method of expansion that included a hollow fiber bioreactor (artificial capillary culture system). Patients received IP TIL suspended in dextrose 5% in sodium chloride 0.2% containing 0.1% human albumin and 6 x 10(5) IU rIL-2 on day 1, followed by 6 x 10(5) IU rIL-2/m2 body surface area, administered daily by bolus IP injection, on days 2-4, 8-11, and 15-18. In the absence of disease progression, two additional 4-day cycles of IP rIL-2 were administered. Patients (n = 3) whose TIL failed to grow in vitro received IP IL-2 alone. Eight patients received rIL-2 expanded TIL (10(10)-10(11) range) plus rIL-2 followed by several cycles of rIL-2 alone. One of these patients was treated twice with TIL plus rIL-2. Expanded TIL were primarily CD3+CD4+TCR alpha beta+ (eight TIL-derived T-cell lines). One TIL-derived T-cell line was comprised mostly of CD3+CD8+TCR alpha beta+ cells. Eleven patients (eight treated with TIL plus rIL-2 and three patients treated with rIL-2 alone) received a total of 38 cycles of rIL-2 without TIL. Grade 3 clinical toxicity (peritonitis) occurred in 1 of 9 cycles of TIL plus rIL-2 and 1 of 38 cycles of rIL-2 alone. Each cycle was 4 days long. Grade 3 anemia occurred in 1 of 9 TIL plus rIL-2 cycles and 3 of 38 cycles of rIL-2 alone. There were no measurable responses; however, four of eight patients treated with IP TIL plus rIL-2 had some indication of clinical activity: ascites regression (two patients), tumor and CA-125 reduction (one patient), and surgically confirmed stable tumor and CA-125 values (one patient). The schedule of IP TIL plus low-dose rIL-2 shows manageable toxicity and is worthy of further evaluation in patients with epithelial ovarian cancer who have less tumor burden.

Adult↗
PubMed1994

Morphonuclear comparison of the mantle zone and diffuse subtypes of mantle cell lymphoma.

Mantle cell lymphoma (MCL) is a distinct type of non-Hodgkin's lymphoma, which, based on the architectural pattern, has been divided into mantle zone (MCL-MZ), allegedly associated with longer survival, and diffuse (MCL-D) subtypes. To determine whether there are morphonuclear differences between MCL-MZ and MCL-D, 37 fine needle aspirates (FNAs) obtained from 32 patients with MCL (21 cases of MCL-MZ and 11 of MCL-D) were evaluated using digital cell image analysis. Twenty-one morphometric parameters related to geometry, color, texture and densitometry were evaluated on 100 cells from each case. Aspirated material was stained with either the Diff-Quik or Feulgen method. Statistical analysis (student's t test and nonparametric Mann-Whitney test) was performed. No significant differences between MCL-MZ and MCL-D were found in any of the 21 studied morphonuclear parameters. The morphometric analysis results were similar using the Diff-Quik and Feulgen techniques. This study confirmed the overlapping cytologic spectrum of MCL-MZ and MCL-D and indicated that histologic specimens demonstrating a specific architectural pattern are necessary to differentiate these two variants of MCL. Either Diff-Quik- or Feulgen-stained tissues may be used for morphonuclear measurements in FNAs of MCL since both give similar results.

Biopsy, Needle↗
PubMed1994

DNA content by image analysis. An accurate discriminator of malignancy in pericardial effusions.

DNA analysis was performed on 20 cytologically equivocal pericardial effusions to determine if it would be a useful ancillary technique in identifying malignancy. Ploidy determination by interactive image analysis showed single diploid DNA peaks, with no cells > 5c, in all eight reactive cases studied. The reactive cases had a mean proliferation index of 1.3. All 12 malignant cases studied had cells with DNA content > 5c. A dominant DNA peak at 2c was present in 25%, dominant aneuploid stem lines were present in 25%, and multiple stem lines were present in 50% of the malignant cases. By image analysis, the presence of DNA content > 5c was both sensitive and specific for detecting malignancy in the group of pericardial effusions evaluated.

Cell Count↗
PubMed1994

Estrogen receptor immunostaining patterns imaged in breast cancer fine needle aspirates.

Fine needle aspirates (FNA) after estrogen receptor (peroxidase-antiperoxidase) immunostaining were imaged using a SAMBA system. Integrated optical density (IOD) and mean optical density (MOD) was measured in individual nuclei. Receptogram R Analytic software on a remote VAX computer was used to generate log-log scatter, contour and three-dimensional perspective plots of bivariate MOD vs. IOD relationships and for count-dependent Gaussian smoothing of the univariate log histograms. The findings revealed four types of staining patterns among otherwise estrogen receptor immunostaining-positive patients: (I) a discrete, homogeneous subpopulation with unimodal MOD and IOD distributions; (II) coexistent subpopulations of ER+ and ER- cells, revealed by bivariate MOD and IOD distributions; (III) multiple, discrete subpopulations of ER+ cells, revealed in perspective plots of MOD vs. IOD vs. scatter density; and (IV) highly skewed distributions forming a continuum over a broad MOD and IOD range with or without an ER-negative subpopulation. FNA ER-ICA-positive specimens were indistinguishable based upon average nuclear MOD (AV-MOD) or AV-MOD x (% ER-positive cells). Previous evaluation of such patterns in tissue sections revealed failure of tamoxifen response in types II and IV. Staining mosaicism (IV) may correspond to a failure of receptor modulation within defined limits when ER is rendered nonfunctional due to various structural modifications of receptor domains--events that would not affect immunostaining. Failure in type II is ascribed to ascendancy of estrogen-independent ER-negative subpopulations.

Biopsy, Needle↗