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Biomedical subjects

R L Katz

Publications and source records attributed to R L Katz.

At least 37 records · Page 2Linked to original sources
PubMed1998

Relationship among cystectomy, microvessel density and prognosis in stage T1 transitional cell carcinoma of the bladder.

PURPOSE: The selection of therapy for stage T1 bladder cancer is controversial, and reliable biomarkers that identify patients likely to require cystectomy for local disease control have not been established. We evaluated our experience with T1 bladder cancer to determine whether early cystectomy improves prognosis, and whether microvessel density has prognostic value for T1 lesions and could be used for patient selection. MATERIALS AND METHODS: We retrospectively reviewed the records of 88 patients with T1 transitional cell carcinoma of the bladder. Patient outcome was correlated with therapeutic intervention. Paraffin embedded tissue from 54 patients was available for factor VIII immunohistochemical staining for microvessel density quantification. RESULTS: Median followup was 48 months (range 12 to 239). Of the patients 34% had no tumor recurrence. The rates of recurrence only and progression to higher stage disease were 41 and 25%, respectively. The survival of patients in whom disease progressed was diminished (p = 0.0002). Grade did not predict recurrence or progression nor did cystectomy provide a survival advantage. Microvessel density did not correlate with recurrence or progression. CONCLUSIONS: Patients with T1 bladder cancer have a high risk of recurrence and progression. Tumor progression has a significant negative impact on survival. Neither grade nor early tumor recurrence predicted disease progression. Because early cystectomy did not improve patient outcome, we suggest reserving cystectomy for patients with progression or disease refractory to local therapy. Microvessel density is not a prognostic marker for T1 bladder cancer and has no value in selecting patients with T1 disease for cystectomy.

Capillaries↗
PubMed1997

Clinical significance of negative and equivocal urinary bladder cytology alone and in combination with DNA image analysis and cystoscopy.

BACKGROUND: We evaluated the individual and combined ability of cytology (CYT), image analysis (IA), and cystoscopy (CYSTO) to predict the presence of transitional cell carcinoma (TCC) at 6 months of follow-up in patients with or without a prior history of urothelial carcinoma and negative (NEG) or equivocal (atypical or suspicious) urinary CYT. METHODS: Fifty-one patients (43 with prior TCC) provided 57 urinary samples that were evaluated by CYT and DNA IA. Forty-nine patients were evaluated by CYSTO. Disease status was reassessed at 6 months by a combination of clinical, CYSTO, CYT, and histologic follow-up. RESULTS: At 6 months' follow-up, the incidence of recurrence for patients with diploid, broad diploid, or aneuploid DNA histograms was 38%, 73%, and 100%, respectively. In the same group of patients, 43% of patients with NEG and "atypical" CYT recurred compared with 83.3% of patients with "suspicious" CYT. The predictive value (PV) of a positive (+) CYSTO evaluation was 100%; however, a NEG CYSTO examination was correct in only 73% of cases. Sensitivities of CYT, IA, and CYSTO to predict recurrence were 54%, 59%, and 62.5%, respectively, whereas the combined sensitivity of all three modalities was 72%. The +PV of combined CYT and IA in patients with prior TCC was 90% with aneuploidy 100% specific for malignancy; the NEG PV of combined CYT, IA, and CYSTO was 70%. CYT, IA, and CYSTO were highly significant in predicting recurrence (P = 0.0017, P = 0.0026, and P = 0.0002, respectively) whereas tumor grade and degree of invasiveness as assessed on initial biopsy were not significant. However, 11% of patients recurred between 6 months to 1 year who had NEG CYT, NEG CYSTO, and NEG IA. CONCLUSIONS: Diagnostic accuracy increases in patients with NEG or equivocal CYT if supplemented by DNA IA and CYSTO. In patients with no history of TCC, equivocal urine CYT and/or abnormal DNA IA can occur after chemotherapy, radiation therapy, or viral infection. In these patients, the combined approach together with accurate history is essential for correct diagnosis. For the small subpopulation of patients who recur but demonstrate no abnormalities on combined testing, more sensitive diagnostic tests, such as chromosomal abnormalities by in situ hybridization, need to be developed.

Adult↗
PubMed1997

Differentiating cytological features of bronchioloalveolar carcinoma from adenocarcinoma of the lung in fine-needle aspirations: a statistical analysis of 27 cases.

Bronchioloalveolar carcinoma (BAC) is an uncommon type of lung carcinoma that is important to distinguish from adenocarcinoma (adenoCA) because of its different biological behavior. Although the features of BAC have often been described in cytological material other than fine-needle aspirations (FNA), they have rarely been detailed in FNA specimens. We undertook to delineate the differentiating cytological features of 13 cases of BAC (7 of the nonsecretory type and 6 of the secretory type) and of 14 cases of bronchogenic adenoCA in FNA material, looking at 17 cytological criteria and using statistical analysis. When statistically analyzed with chi-square and Pearson's correlation, only 3 of the 17 features were found to be good discriminants for distinguishing nonsecretory BAC (NS-BAC) from adenoCA: prominence of monolayered tumor sheets, fine chromatin pattern, and mild cellular pleomorphism correlated significantly with NS-BAC. On the other hand, only the prominence of nuclear grooves and the abundance of extracellular mucin correlated significantly with secretory BAC (S-BAC) when compared to adenoCA. When using a logistic regression analysis, NS-BAC and S-BAC were best discriminated from adenoCA by the prominence of monolayered tumor sheets and by the abundance of extracellular mucin, respectively. We conclude that, in most instances, it is possible to make an accurate diagnosis of BAC and to distinguish it from adenoCA of the lung in FNA material.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed1997

Concomitant lymphoma and metastatic carcinoma in a lymph node: diagnosis by fine-needle aspiration biopsy in two cases.

Concomitant lymphoma and metastatic carcinoma are an unusual occurrence in a lymph node. We report two patients in whom synchronous malignancies were diagnosed by fine-needle aspiration biopsy (FNAB). In one case, the FNAB diagnoses of both small lymphocytic lymphoma and metastatic breast carcinoma were the initial diagnoses. In the second case, metastatic poorly differentiated squamous carcinoma was an unexpected finding in a patient with a history of small lymphocytic lymphoma. The aspirates in both cases showed two distinct cell populations, one consisting of a dispersed population of small uniform lymphoid cells and the other comprising large atypical single cells and cohesive clusters of epithelial cells. In both cases, the cytologic diagnoses were supported by immunohistochemical and flow cytometric studies.

Biopsy, Needle↗
PubMed1997

Spinal artery syndrome masked by postoperative epidural analgesia.

PURPOSE: We report a case of a patient who developed a postoperative anterior spinal artery syndrome that was masked by the use of epidural analgesia. We wish to alert other anaesthetists that the use of epidural anaesthesia in this setting may mask the symptoms and delay the diagnosis of this rare complication. CLINICAL FEATURES: The patient was a 22-yr-old obese man with metastatic testicular carcinoma who underwent a left-sided thoracoabdominal retroperitoneal tumour resection. A lumbar epidural catheter was placed preoperatively for pain management. Postoperatively, the patient developed bilateral lower extremity weakness, which was at first attributed to epidural administration of local anaesthetics. Despite discontinuation of the local anaesthetics, the symptoms persisted. Further work-up led to the diagnosis of anterior spinal artery syndrome. The patient was sent to a rehabilitation hospital and had a partial recovery. CONCLUSION: Anterior spinal artery syndrome can occur following retroperitoneal surgery. It is important to recognize the potential for this complication when postoperative epidural analgesia is contemplated, especially following a left-sided surgical dissection. The use of epidural local anaesthetics immediately after surgery delays the diagnosis of a postoperative neurological deficit. Moreover, when the deficit is recognized the epidural itself may be falsely blamed for postoperative paraplegia. If epidural analgesia is used, opioids may be preferred over local anaesthetics in the immediate postoperative period to prevent masking of an anterior spinal artery syndrome.

Adult↗
PubMed1997

An intra-abdominal small round cell neoplasm with features of primitive neuroectodermal and desmoplastic round cell tumor and a EWS/FLI-1 fusion transcript.

We report an intra-abdominal round cell tumor in a young man which exhibited the light and electron microscopic appearance of a peripheral primitive neuroectodermal tumor (PNET), in addition to the clinical and topographic characteristics, desmoplasia and a complex immunophenotypic profile of the intra-abdominal desmoplastic round cell tumor (DSRCT). Reverse transcription polymerase chain reaction revealed a EWS/FLI-1 fusion transcript as in PNET/Ewing's sarcoma, instead of the EWS/WT1 transcript of DSRCT. The tumor was also strongly positive for the mic2 protein. This is a unique case of a hybrid tumor arising in the peritoneal cavity of a young male. The existence of such a hybrid tumor in this location suggests that DSRCT and PNET may be related and possibly share a common histogenesis.

Abdominal Neoplasms↗
PubMed1997

Systemic physostigmine increases the antinociceptive effect of spinal morphine.

In this study we evaluated the antinociceptive effect of concurrent intrathecal (i.t.) and subcutaneous (s.c.) administration of morphine and physostigmine, respectively. The experiments were performed on male Wistar rats. Intrathecal administration of morphine was performed through a catheter implanted in the subarachnoid space. The 'tail-immersion' test was used to measure animals' responses to evoked nociceptive stimuli. Interaction of drugs was analyzed using a dose addition model. Both i.t. (1-5 microg) administration of morphine and s.c. (50-250 microg/kg) administration of physostigmine increased the latencies of nociceptive responses in a dose-dependent manner. Two micrograms of i.t. morphine and 100 microg/kg of s.c. physostigmine demonstrated 31.6 +/- 10.6 and 34.2 +/- 11.4 percentage of maximal possible effect (%MPE), respectively. Simultaneous administration of 1 microg of i.t. morphine and 50 microg/kg of s.c. physostigmine produced a %MPE equal to 84.8 +/- 16.9. Thus, combined administration of 1 microg i.t. morphine and 50 microg/kg s.c. physostigmine resulted in a strong, highly significant antinociceptive effect. This effect was much higher than the effect expected if both drugs acted in an additive manner. Supra-additive interaction observed in this study might be a result of simultaneous activation of different neurotransmitter systems involved in nociceptive processing at the spinal as well as at the supraspinal level of the CNS.

Analgesics, Opioid↗
PubMed1997

Strong correlation between c-erbB-2 overexpression and overall survival of patients with oral squamous cell carcinoma.

Overexpression of c-erbB-2 (also known as HER-2/neu) has been found in many human cancers, including head and neck squamous cell carcinoma (SCC). We therefore examined expression of the oncoprotein in oral SCC primary tumor samples and compared its relationship with clinical stages and survival rate. Out of 80 cases of oral SCC, high expression level (++ or +++) of c-erbB-2 was found in 41 cases. Of the 80 cases with follow-up information, 39 were further investigated for the correlation of expression level of c-erbB-2 and survival rate. Overexpression of the oncoprotein was significantly correlated with shorter overall survival, and the patients with low and no expression of c-erbB-2 had much higher survival rates. Overexpression of c-erbB-2 was also significantly correlated with nodal stage and metastasis. We found that high expression level of c-erbB-2 was frequently detected in oral cancer cell lines but not in the other head and neck SCC cell lines. Thus, we conclude that overexpression of c-erbB-2 is a frequent event in oral SCC and is correlated with poor survival and may be used as a poor prognostic factor.

Adolescent↗
PubMed1997

Effect of recombinant alpha-interferon on pharmacokinetics, biodistribution, toxicity, and efficacy of 131I-labeled monoclonal antibody CC49 in breast cancer: a phase II trial.

Preclinical studies have demonstrated that recombinant IFN-alpha (rIFN-alpha) can enhance the tumor associated glycoprotein 72 (TAG-72) on tumors. To determine whether rIFN-alpha could enhance TAG-72 expression in vivo in patients, 15 women with breast cancer were randomized to receive daily injections of rIFN-alpha (3 x 10(6) units/m2 for 14 days) beginning on day 1 (group 1 = 7 patients) or on day 6 (group 2 = 8 patients). On day 3, all patients received a 10-20-mCi tracer dose of 131I-CC49, a high-affinity murine monoclonal antibody reactive against TAG-72, followed by a therapy dose of 60-75 mCi/m2 of 131I-CC49 on day 6. Whole body and single-photon emission computed tomography scans along with whole blood pharmacokinetics were performed following tracer and treatment phases. Hematological toxicity was considerable; reversible grade 3-4 neutropenia and thrombocytopenia was observed in 12 of 15 patients. Twelve of 14 patients tested developed human antimouse antibodies 3-6 weeks after treatment. For group 1 patients, whole blood residence time increased significantly between that predicted from the tracer doses and therapy doses (42.6 +/- 4.7 versus 51.5 +/- 4.8 h, respectively; P < 0.01). The calculated radiation absorbed dose to red marrow from therapy compared to tracer activity was also significantly higher for this group (1.25 +/- 0.35 versus 1. 07 +/- 0.26 cGy/mCi; P < 0.05). Treatment with rIFN-alpha was found to enhance TAG-72 expression in tumors from patients receiving rIFN-alpha (group 1) by 46 +/- 19% (P < 0.05) compared to only 1.3 +/- 0.95% in patients not initially receiving IFN (group 2). The uptake of CC49 in tumors was also significantly increased in rIFN-alpha-treated patients. One partial and two minor tumor responses were seen. In summary, rIFN-alpha treatment altered the pharmacokinetics and tumor uptake of 131I-CC49 in patients at the expense of increased toxicity.

Adult↗
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↗