Utility of eosinophil count as predictor of bacteremia.
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Adult↗
Biomedical subjects
Anil Potti
Publications and source records attributed to Anil Potti.
Clinical course of lung cancer in patients with chronic kidney disease.
Co-morbidity has a major impact on survival in early and late-stage lung carcinoma. Patients maintained on dialysis are potentially at increased risk of cancer. However, since very few studies have examined the clinical course of lung cancer in patients with chronic kidney disease (CKD), we felt it was important to study the course of non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) in this patient population. We performed a retrospective chart review of patients diagnosed with lung cancer and co-existent CKD. 107 patients (101 males and six females), with a mean age at diagnosis of 69 years (range: 39-86 years) were included in our study. Of these, 17 (15.9%) patients had SCLC while 87 (81.3%) had NSCLC. Dyspnea, weight loss, and chest pain were the most common symptoms at presentation in our patient population occurring in 25, 20, and 15% of patients, respectively. The median survival of all the patients in the study was 10 months (range: 0-116 months). Patients with SCLC had a median survival of 7 months. Patients with NSCLC had a median survival of 10 months. We found that the clinical course and survival in patients with lung cancer and CKD appear to be comparable to that of patients with lung cancer, but without kidney dysfunction. Hence though treatment of lung cancer does need to be individualized in the setting of CKD, it should not dissuade the clinician from treating the malignancy.
Adult↗
Determination of HER-2/neu overexpression and clinical predictors of survival in a cohort of 347 patients with primary malignant brain tumors.
INTRODUCTION: HER-2/neu overexpression has been associated with poor prognosis in a variety of malignancies. The extent and relevance of HER-2/neu overexpression in human central nervous system (CNS) malignancies is unclear. We retrospectively analyzed a large cohort of patients with primary malignant brain tumors to evaluate the role of HER-2/neu overexpression, clinical characteristics at presentation, and other predisposing factors as predictors of survival. MATERIALS AND METHODS: Records of 347 adult patients (193 males, 154 females) diagnosed and followed between 1986 and 2001 with a biopsy-proven diagnosis of a primary malignant brain tumor at a tertiary care oncology center were reviewed. Archival pathologic samples were analyzed for HER-2/neu overexpression using the Hercep immunohistochemical (IHC) assay (DAKO). A score of 2+ or greater on the assay was considered positive for HER-2/neu overexpression. Mortality and its predictors were evaluated using multiple logistic regression. (This study was approved and reviewed by the Institutional Review Board Committee [IRB] of University of North Dakota School of Medicine and Health Sciences.) RESULTS: Among the 347 adult patients with a mean age of 53 years (range; 41-73 years), overall mean survival was 23 months (range; 0-151 months). It was found that 10.4% of the archival pathologic samples showed presence of HER-2/neu overexpression by IHC. The HER-2/neu overexpression predicted significantly increased mortality [p = 0.01, analysis of variance (ANOVA)]. Other clinical predictors associated with increased mortality included site of tumor (occipital and parietal lobes) (p = 0.02, ANOVA), tumor histology (glioblastoma) (p < 0.01, ANOVA), and presenting symptom (nausea/vomiting) (p < 0.01, ANOVA). Also, there was a higher incidence of associated primary malignancies (outside the CNS) in the HER-2/neu overexpression group (30% vs. 7%). CONCLUSIONS: HER-2/neu overexpression seen in 10.4% appears to predict a slight increased mortality in patients with primary malignant brain tumors, especially glioblastoma multiforme, and is associated with a high incidence of a second primary malignancy outside the CNS. Additionally, our data suggests that other clinical variables were predictive of increased mortality, including tumor location (occipital), histology (glioblastoma), and presenting symptoms (nausea/vomiting). The large, heterogeneous sample employed in our study allows more definitive conclusions to be made with regard to the usefulness of HER-2/neu and other clinical predictors of survival in patients with primary brain tumors.
Adult↗
Role of her-2/neu overexpression and clinical features at presentation as predictive factors in meningiomas.
Prediction of outcome in patients with meningiomas remains a significant problem to date. We have evaluated the role of symptoms at presentation and overexpression of her-2/neu overexpression as independent prognostic factors in meningiomas. In a retrospective study on patients with biopsy-proven diagnosis of meningioma, her-2/neu overexpression was evaluated using immunohistochemistry (IHC) performed on paraffin-embedded specimens. An IHC score of > or =2+ was considered positive for overexpression. Two hundred thirty-seven patients thus identified between January 1986 and December 1999 included 149 females and 88 males, with a mean age of 63.44 years. Survival was estimated using the Kaplan-Meier method. Incidence of meningiomas in females (62.8%) was significantly greater than in males. Focal neurodeficits, headache, and seizures (39.66%) were the most common presenting complaints and were not related to tumor behavior/outcome. Syncope at presentation was associated with a decreased survival, but this symptom constituted only 2.53% of the total, so reliable conclusions could not be drawn. Only 6 (2.53%) specimens revealed HER-2/neu overexpression by IHC. HER-2/neu overexpression is not a predictor of tumor behavior and has no role as a prognostic factor in meningiomas. Syncope as the clinical presentation at diagnosis may predict a poor outcome, but needs further investigation.
Adolescent↗
Regulatable aptamers in medicine: focus on antithrombotic strategies.
Proteins generally execute the key physiological activities required for normal growth and homeostasis. As such, many different classes of proteins, including proteases, kinases, cellular receptors and signalling proteins, represent attractive targets for diagnosis or therapy. Aptamers are small nucleic acid molecules that function as direct protein inhibitors, much like monoclonal antibodies. After a decade of intensive research, technology development and initial clinical evaluation, aptamers have now demonstrated broad potential as direct protein ligands and inhibitors, and thus represent an exciting class of compounds for the development of new therapeutic and diagnostic agents. This review will discuss the basic properties and isolation of aptamers, their use in animals and the clinic, and describe an exciting recent advance in the development of antidotes to certain aptamers, which will add a repertoire of new agents with regulatable activity for clinical use.
Anticoagulants↗
Immunohistochemical determination of HER-2/neu, c-Kit (CD117), and vascular endothelial growth factor (VEGF) overexpression in malignant melanoma.
PURPOSE: To determine the prevalence and evaluate the possible prognostic value of the molecular targets in malignant melanoma, we studied the overexpression of HER-2/neu, c-Kit, and vascular endothelial growth factor (VEGF) in this patient population. MATERIALS AND METHODS: Overexpression of HER-2/neu, c-Kit, and VEGF was evaluated using immunohistochemical assays in 202 archival tissue specimens. RESULTS: Only two patients (0.9%) revealed HER-2/neu overexpression, whereas 46 (22.8%) revealed c-Kit and 42 (20.8%) specimens showed VEGF overexpression. Multivariate analysis performed did not show a significant difference in survival between c-Kit-positive and c-Kit-negative groups (P = 0.36) and VEGF-positive and VEGF-negative groups (P = 0.25). Interestingly, c-Kit was more likely to be overexpressed in the superficial spreading type and VEGF was overexpressed preferentially in the amelanotic melanoma type. CONCLUSIONS: HER-2/neu has no role in melanogenesis. Both c-Kit (expressed in superficial spreading disease) and VEGF (expressed in amelanotic melanoma) may have significant therapeutic implications as molecular targets, which warrants further investigation.
Biomarkers, Tumor↗
Immunohistochemical determination of HER-2/neu overexpression in malignant melanoma reveals no prognostic value, while c-Kit (CD117) overexpression exhibits potential therapeutic implications.
BACKGROUND: HER-2/neu and c-kit (CD117) onco-protein are increasingly being recognized as targets for therapy in solid tumors, but data on their role in malignant melanoma is currently limited. We studied the prevalence of overexpression of HER-2/neu and c-Kit in 202 patients with malignant melanoma to evaluate a possible prognostic value of these molecular targets in malignant melanoma. METHODS: Overexpression of HER-2/neu and c-Kit was evaluated using immunohistochemical assays in 202 archival tissue specimens. RESULTS: Between 1991 and 2001, 202 subjects (109 males; 54% and 93 females; 46%) with malignant melanoma were studied with a mean age of 57 years (age range: 15-101 years). The most common histologic type was amelanotic melanoma (n = 62; 30.7%) followed by superficial spreading melanoma (n = 54; 26.7%). The depth of penetration of melanoma (Breslow thickness, pT Stage) ranged from 0.4 mm (stage pT1) to 8.0 mm (stage pT4A). Mean thickness was 2.6 mm (stage pT3A). The ECOG performance scores ranged from 0 to 3. Only 2 patients (0.9%) revealed HER-2/neu overexpression, whereas 46 (22.8%) revealed c-Kit overexpression. Multivariate analysis performed did not show a significant difference in survival between c-Kit positive and negative groups (p = 0.36). Interestingly, not only was c-Kit more likely to be overexpressed in the superficial spreading type, a preliminary association between the presence or absence of c-Kit overexpression and the existence of another second primary tumor was also observed. CONCLUSIONS: The results of our large study indicate that the HER-2/neu onco-protein neither has a role in melanogenesis nor is a potential target for clinical trials with monoclonal antibody therapy. This indicates there is no role for its testing in patients with malignant melanoma. Although c-Kit, expressed preferentially in the superficial spreading type, may not have prognostic value, it does have significant therapeutic implications as a molecular target warranting further investigation.
Journal Article↗
Determination of vascular endothelial growth factor (VEGF) overexpression in soft tissue sarcomas and the role of overexpression in leiomyosarcoma.
PURPOSE: To evaluate the prevalence and role of vascular endothelial growth factor (VEGF) overexpression in soft tissue sarcoma (STS). PATIENTS AND METHODS: VEGF expression was detected by the avidin-biotin-complex method using Santa Cruz biotechnology (SC 7629). The expression of VEGF was assessed according to the percentage of immunoreactive cells: more than 10% of the cells staining were graded as positive. No detectable staining or <10% (of cells) staining was graded as negative. RESULTS: Two hundred and seventy-three patients (164 females and 109 males) with a mean age of 56 years (range: 1-93 years) were included in the study. Sixty-eight of the 273 (24.91%) patients diagnosed with STS between 1986 and 2001 revealed VEGF overexpression. VEGF overexpression was predominantly seen in 30% (15/50) of patients with malignant fibrous histiocytoma (MFH), 20.45% (9/44) of dermatofibrosarcomas (DFS), 25% (9/36) of leiomyosarcomas (LMS), and 30% (6/20) of patients with carcinosarcomas (CS). Despite overexpression being seen in about a quarter of patients with STS, VEGF overexpression was of prognostic value in only those patients with the LMS histologic type, as VEGF overexpression was associated with a shorter survival in this subgroup( P=0.01, by log-rank sum test). CONCLUSION: Twenty-four point nine percent of STS overexpress VEGF and interestingly there is diversity seen in VEGF expression amongst the various histologic subtypes of STS. LMS, CS, and MFH are more likely to reveal overexpression of VEGF than the other histologic subtypes. There was no relationship between survival and VEGF status in any subtype of STS, except LMS. There is an urgent need for larger studies to validate our findings. In addition, randomized clinical trials evaluating the efficacy of angiogenesis inhibitors in soft tissue sarcomas, especially LMS, are warranted.
Adolescent↗
Effect of pesticide exposure on HER-2/neu overexpression seen in patients with extensive stage small cell lung carcinoma.
PURPOSE: The aim of this study was to evaluate the relationship, if any, between pesticide exposure and overexpression of the HER-2/neu oncoprotein in extensive stage small cell lung cancer (ESSCLC). EXPERIMENTAL DESIGN: The records of all patients with a diagnosis of ESSCLC from January 1991 through April 2001 were reviewed in our retrospective study. Pesticide risk (herbicide and insecticide) was assessed by telephone interviews using a predetermined questionnaire with emphasis on type of exposure, use of protective measures, and duration of exposure. An exposure index was calculated (h/day x days/year x years), and patients with an index > 2400 h were considered as exposed. HER-2/neu overexpression was assessed by immunohistochemistry using the Hercep test developed by Dako. Statistical analysis was performed using SPSS-10. RESULTS: A total of 193 patients (84 females and 109 males), with a mean age of 68.5 years (range, 42-90 years) were included in the study. Of these, 57 (29.5%) revealed HER-2/neu overexpression by immunohistochemistry. After adjusting for age, smoking, Eastern Cooperative Oncology Group score, and treatment, HER-2/neu overexpression was associated with a statistically significant diminished survival (P < 0.001; Mann-Whitney U test). We contacted 53 of 57 patients with overexpression and 121 of 136 patients without HER-2/neu overexpression to ascertain a history of pesticide exposure. Forty-one of 53 (77.4%) patients with HER-2/neu overexpression and 47 of the 121 patients without overexpression (38.8%) were exposed to pesticides. We found that patients with history of pesticide exposure had a higher risk of having HER-2/neu overexpression (odds ratio, 5.38; P < 0.01, 95% confidence interval, 2.5-11.2) CONCLUSIONS: HER-2/neu is overexpressed in approximately 30% patients with ESSCLC and is associated with decreased survival. Also, pesticide exposure seems to be related to HER-2/neu overexpression seen in our patient population. Future studies are needed to validate our findings and also to determine which pesticide(s)/pesticide components are actually responsible for HER-2/neu overexpression seen in ESSCLC.
Adult↗
Prevalence of pesticide exposure in young males (</= 50 years) with adenocarcinoma of the prostate.
Evidence implicating pesticides as causative agents of prostate cancer is controversial, and specifically, data in young adults is lacking. Hence, we performed a preliminary study evaluating the relationship between pesticide exposure and prostate cancer in young males. After approval from the University of North Dakota Institutional Review Board and Human Subjects Committee, a retrospective study was performed on all young males (</ = 50 years) with a biopsy-proven diagnosis of carcinoma of the prostate. The records of all patients aged less than/equal to 50 years, with a diagnosis of adenocarcinoma of the prostate, from January 1991 through December 2001 were reviewed. Pesticide risk assessment interviews were performed by a single member of the team, for consistency, via telephone on the basis of a pre-determined questionnaire investigating occupations and hobbies with special emphasis on: Duration of exposure. An exposure index was calculated for each interviewed subject according to the following formula: hours/day x days/year x years. Patients with an exposure index >2400 hours were considered as 'exposed.' The 2400 hour cut-off value was chosen on the basis of previous reports indicating that this figure represents heavy exposure to genotoxic agents. Statistical analysis was obtained using SPSS-10ledR;. Between 1991 and 2001, 61 young males with adenocarcinoma of the prostate were identified, of whom 56 patients with a mean age of 47 years (range: 40-49) had complete records of treatment and could be contacted for completion of the questionnaire. The most common stage at presentation was Stage III and the mean Gleason's score was 7.5 (range 5-9). Interestingly, almost a third (16/56, 28.6%) of patients had stage IV disease at presentation. 37/56 (66.1%) patients had 'significant' exposure in our study. In addition, interestingly, the mean survival in the subgroup of patients with pesticide exposure was 11.3 months (SD: +/- 2.3 months), while the mean survival in the patients without pesticide exposure (n = 19) was 20.1 months (SD: +/- 3.1 months), with p-value <0.01. Although our study is relatively small, it does reveal preliminary evidence linking pesticide exposure to the early development of, possibly aggressive, prostate adenocarcinoma. Future, larger, epidemiological studies are needed to confirm the findings of our study.
Journal Article↗
An indolent B-cell lymphoma with t(2;8)(p12;q24) abnormality and absence of C-MYC amplification and TP53 deletion. A new variant?
The translocation between chromosomes 2 and 8, t(2;8), is well known for its strong association with high-grade Burkitt lymphoma. However, the significance of this translocation in indolent lymphoproliferative disorders is not clear. We present the case of a 75-year-old white male with left upper quadrant abdominal pain, splenomegaly, and an elevated white cell count of 30.3x10(9) cells/L (84% large lymphoid cells with scanty cytoplasm and prominent central nucleoli). Immunophenotyping revealed a clonal B-cell population coexpressing CD5, CD19, and CD20 with weak CD23 and CD25 and very weak, restricted, surface lambda. The cytogenetic analysis showed all 20 cells with t(2;8)(p12;q24.3). In addition, four of the 20 cells also showed a second translocation: t(12;17)(p13;q21). Molecular analysis using c-myc and p53 probes showed normal results with no indication of amplification of C-MYC or deletion of TP53. The patient was managed as an indo-lent/low-grade lymphoproliferative disorder with excellent response to eight cycles of fludarabine.
Aged↗
Myeloproliferative syndromes and the associated risk of coronary artery disease.
INTRODUCTION: Of the major myeloproliferative syndromes (MPS) [polycythemia vera (PV), essential thrombocythemia (ET), chronic myeloid leukemia (CML) and myelofibrosis (MF)], PV and ET are reported to be associated with increased thrombotic complications. However, the relationship between these myeloproliferative syndromes and coronary artery disease (CAD) is unclear. METHODS: We performed a retrospective chart review to evaluate the prevalence of CAD in patients with diagnosed with MPS between 1991 and 2001. RESULTS: One hundred and eighty-one patients (100 males, 81 females) with a mean age of 72.5 years were included. Twenty-nine patients, 19 males and 10 females (16%, 95% CI: 12.0-24.0) had CAD. These included 6/53 (11.3%, 95% CI: 1.5-20.2) patients with CML, 1/26 (3.8%, 95% CI: -4.4 to 12.8) patients with PV, 5/30 (16.7%, 95% CI: 2.5-30.8) patients with ET, 3/7 (42.9%, 95% CI: 12.3-87.7) patients with MF and 14/65 (21.5%, 95% CI: 13.1-37.8) patients with co-existent MPS. Comparing the risk of CAD with CML as a baseline, MF had an OR of 8.2 (p < 0.01, 95% CI: 1.7-39), PV-0.4 (p = 0.4, 95% CI: 0.04-3.2), ET-1.6 (p = 0.7, 95% CI: 0.43-6.2) and patients with co-existent MPS-2.8 (p=0.07, 95% CI: 0.91-8.6). However, after adjusting for age, sex, dyslipidemia, diabetes, hypertension and tobacco use, the difference in the prevalence of CAD between the various categories of MPS was not significant. CONCLUSION: Contrary to conventional belief, we did not find an increased prevalence of CAD in patients with either PV or ET. In fact, patients with MF had a significantly higher prevalence of CAD. However, this difference appears to be due to the increased age at diagnosis of MF. The conventional risk factors for CAD appear to be the major determinants of CAD among patients with MPS.
Aged↗
Challenging and unusual cases: Case 1. Simultaneous presentation of acute myelogenous leukemia and myocardial infarction.
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Humans↗
Unusual abdominal tumors: case 1. Small bowel carcinoid presenting as an acute abdomen.
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Abdomen, Acute↗
Uncommon presentations of non-Hodgkin's lymphoma: case 3. Primary renal lymphoma.
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Aged↗
Uncommon syndromes and treatment manifestations of malignancy: Case 4. Periorbital edema and imatinib mesylate therapy for chronic myelogenous leukemia.
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Aged↗
Uncommon syndromes and treatment manifestations of malignancy: Case 2. Metastatic non-small-cell lung cancer presenting with leukocytosis.
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Biomarkers, Tumor↗
Chromosomal anomalies in two coexistent myeloproliferative disorders.
A 58-year-old male presented with fatigue, tiredness, and pruritus after hot showers and an elevated white blood cell count (20000/mm(3)). A diagnosis of polycythemia vera (PV) was made after investigation revealed a low erythropoietin and elevated leukocyte alkaline phosphatase (LAP) score; he was treated with repeated phlebotomies. Two years later he developed elevated white counts again and investigation revealed Philadelphia chromosome positive (19/20 cells) chronic myelocytic leukemia (CML). The karyotype also revealed trisomy 9 in 1 of 20 cells. He was treated with imatinib mesylate and went into clinical, hematologic, cytogenetic, and molecular remission. Repeat chromosomal analysis revealed absence of Philadelphia chromosome and BCR/ABL translocation but presence of trisomy 9. To our knowledge, this is the first reported case of coexisting PV and CML both associated with separate chromosomal abnormalities. This also raises an interesting therapeutic consideration of using concomitant imatinib mesylate and hydroxyurea.
Chromosomes, Human, Pair 9↗