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Biomedical subjects

Apar Kishor Ganti

Publications and source records attributed to Apar Kishor Ganti.

At least 19 recordsLinked to original sources
PubMed2007

Hematopoietic stem cell transplantation for Hodgkin's disease in a patient with dysfibrinogenemia and thrombosis.

INTRODUCTION: Dysfibrinogenemia is a disorder of fibrinogen structure and is associated with a functional abnormality. Since fibrinogen is a key component of both the procoagulant and fibrinolytic pathways, defects in fibrinogen function can be associated with increased risk for both hemorrhage and thrombosis. Management of patients with dysfibrinogenemia and a thrombotic tendency usually involves long-term anticoagulation. CASE: A 36-year-old male with relapsed nodular sclerosing Hodgkin's was found to have a prolonged prothrombin time, low fibrinogen activity and a normal fibrinogen antigen during evaluation for a hematopoietic peripheral blood stem cell transplant. His past medical history was significant for an acute myocardial infarction and two episodes of acute pancreatitis. His father had dysfibrinogenemia complicated by multiple thrombotic episodes. A trans-esophageal echocardiogram revealed two thrombi, one each in the superior vena cava and the descending aorta. He was treated with enoxaparin and received peripheral blood stem cell transplantation. An effort was made to maintain his fibrinogen activity levels at 200 mg/dL using cryoprecipitate. A month following the transplant he developed a new thrombus in the right internal jugular vein, while on enoxaparin and he was started on argatroban and cryoprecipitate followed by fondaparinux. A repeat echocardiogram six weeks later demonstrated that the burden of thrombus both in the right atrium and descending aorta was significantly lower. DISCUSSION: This is the first case report of a patient with dysfibrinogenemia undergoing peripheral blood stem cell transplantation. Conventional anticoagulant therapy and cryoprecipitate seem to be a reasonable management strategy to prevent thrombosis in a patient with dysfibrinogenemia and a thrombophilic tendency. Secondly, fondaparinux can be used in cases of failure of therapy with low molecular weight heparins and may actually be superior to low molecular weight heparins, especially in patients with dysfibrinogenemia.

Adult↗
PubMed2006

Targeted therapy in advanced non-small cell lung cancer (NSCLC): where do we stand?

Cytotoxic chemotherapy has helped improve the outcomes in patients with advanced non-small cell lung cancer (NSCLC), but we seem to have reached a plateau with respect to the benefit obtained. Also, a large subset of elderly patients and those with a poor performance status cannot tolerate these drugs at recommended doses. There is a growing need to incorporate newer drugs with different mechanisms of action and better safety profile. The epidermal growth factor receptor family (EGFR) and vascular endothelial growth factor (VEGF) have been identified as potential targets and agents acting specifically against these targets have been developed with the hope of improving outcomes. Although recent data with the small molecule EGFR tyrosine kinase inhibitors have been disappointing, there have been instances of dramatic responses thereby raising questions about the ideal patient to whom these drugs should be administered. Cetuximab, the anti-EGFR antibody has shown promising results. Bevacizumab, the anti-VEGF antibody was the first drug to demonstrate a survival benefit in first line treatment when added to chemotherapy. This review will briefly discuss the important trials using these targeted agents in advanced NSCLC.

Angiogenesis Inhibitors↗
PubMed2006

Adjuvant chemotherapy for early-stage non-small cell lung cancer: the past, the present and the future.

Complete resection is mandatory in order to achieve a cure in patients with early-stage non-small cell lung cancer (NSCLC). However, despite complete resection, a substantial proportion of patients have disease recurrence, with distant metastases being the primary sites of failure. Recent trials have conclusively demonstrated the benefit of platinum-based adjuvant therapy in patients with resected stage IB and II NSCLC. The role of adjuvant chemotherapy in resected stage III NSCLC is less clear, with trials showing conflicting results. The role of targeted agents in this setting is being investigated. Gene expression profiling studies should help direct chemotherapy to those who would actually benefit from it, thereby saving others from unnecessary toxicity.

Carcinoma, Non-Small-Cell Lung↗
PubMed2006

Lung cancer screening.

Advances in imaging technology have ushered in a new era for lung cancer screening in high-risk individuals using computed tomographic (CT) scans. Although most published studies are nonrandomized observational cohorts of volunteers, the ability of CT scans to detect early stage lung cancer is undisputable. What is unresolved is the ability of spiral CT screening to affect lung cancer-related mortality. A large randomized trial sponsored by the National Cancer Institute to address this question is currently under way. Genomic and proteomic approaches promise to complement the ability of spiral CT to detect early lung cancer in the next few years. Currently, the decision to screen for lung cancer should involve a careful discussion with the individuals involved about the potential advantages, costs, and drawbacks of the approach.

Cost-Benefit Analysis↗
PubMed2005

Hormone replacement therapy is associated with decreased survival in women with lung cancer.

PURPOSE: Lung cancer is the leading cause of cancer-related death in women. Hormone replacement therapy (HRT) is frequently prescribed to postmenopausal women, but there is little data on its effect on lung cancer. Hence, we conducted a retrospective study to examine the impact of HRT on the natural history of lung cancer. METHODS: We conducted a retrospective chart review of women diagnosed with lung cancer between January 1994 and December 1999. Data collected included age, stage, past history of cancer, smoking history, family history of cancer, HRT use, treatment, and overall survival. The effects of various clinical features on survival were examined using Cox proportional hazards regression models. RESULTS: Four hundred ninety-eight women (median age, 67 years; range, 31 to 93 years) with lung cancer were included. A history of smoking was present in 429 women (86%), whereas 86 women (17%) had taken HRT. Women with lung cancer who received HRT were younger than women with lung cancer who never received HRT (63 v 68 years old, respectively; P < .0001). Overall survival was significantly higher in patients with no HRT compared with patients who received HRT (79 v 39 months, respectively; hazard ratio = 1.97; 95% CI, 1.14 to 3.39). This effect seemed to be more pronounced in women with a smoking history. CONCLUSION: HRT may affect outcomes from lung cancer adversely. Further studies examining the role of HRT use on outcomes from lung cancer, especially in women with a history of smoking, are urgently needed to clarify this important problem.

Adult↗
PubMed2005

HER-2/neu and CD117 (c-kit) overexpression in patients with pesticide exposure and extensive stage small cell lung carcinoma (ESSCLC).

BACKGROUND: The rate of detection of HER-2/neu and CD117 (c-kit) overexpression in small cell lung cancer (SCLC) has varied widely; between 5-35% and 21-70% respectively. METHODS: To evaluate the relationship between pesticide exposure and HER-2/neu and CD117 overexpression in extensive stage SCLC (ESSCLC), we identified patients with ESSCLC and assessed pesticide exposure using a predetermined questionnaire. An exposure index (hours/day x days/year x years) > or = 2400 hours was considered as 'exposed.' HER-2/neu overexpression was evaluated on archival tissue using the DAKO Hercep test, and CD117 testing was performed using immunohistochemistry (A4052 polyclonal antibody). RESULTS: 193 ESSCLC patients were identified. Pesticide exposure data could be obtained on 174 patients (84 females and 109 males) with a mean age of 68.5 years. 53/174 (30.4%) revealed HER-2/neu overexpression. 54/174 (31.03%) specimens showed CD117 overexpression by IHC. On multivariate analysis, HER-2/neu overexpression was associated with diminished survival (p < 0.001). In comparison, CD117 expression did not have an adverse prognostic value (p = 0.025). 41/53 (77.4%) patients with HER-2/neu overexpression and 47/121 (38.8%) patients without overexpression had exposure to pesticides (odds ratio: 5.38; p < 0.01). Among the cohort tested for CD117, 29/54 (53.7%) patients with CD117 overexpression and 59/120 (49.2%) patients without CD117 overexpression had pesticide exposure (odds ratio: 1.18; p = 0.12). CONCLUSION: Pesticide exposure affects HER-2/neu but not CD117 overexpression. Future studies are needed to determine specific pesticide(s)/pesticide components that are responsible for HER-2/neu overexpression in ESSCLC, and to validate our findings in other solid tumors that overexpress HER-2/neu.

Journal Article↗
PubMed2005

Successful hematopoietic stem-cell transplantation in multicentric Castleman disease complicated by POEMS syndrome.

A 39-year-old male presented with pedal edema, pleural effusion, splenomegaly, and generalized lymphadenopathy. Serum protein electrophoresis demonstrated the presence of a monoclonal protein. Histological examination of the spleen following splenectomy showed multifocal vascular proliferation and angiovascular lesions consistent with multicentric Castleman disease. He was treated with steroids and rituximab, but without improvement. The patient was found to have portal venous thrombosis and lower extremity arterial thrombosis. He then received combination chemotherapy with cyclophosphamide and mitoxantrone but developed a severe inflammatory polyneuropathy that left him disabled and wheelchair-bound. A diagnosis of multicentric Castleman disease with POEMS syndrome was made, and he then received high-dose chemotherapy with melphalan followed by autologous peripheral blood stem-cell transplantation. Following transplantation, his nerve conduction studies improved and his serum protein electrophoresis normalized. He is currently ambulatory and does not need wheelchair assistance. Hematopoietic stem-cell transplantation may be a treatment option for patients with multicentric Castleman disease and POEMS syndrome.

Adult↗
PubMed2005

Epidermal growth factor inhibition in solid tumours.

The epidermal growth factor receptor (EGFR) plays an important role in the carcinogenesis of many human malignancies and is therefore an attractive target against which anticancer therapy may be effective. At present, there are two ways in which this may be achieved clinically: antibodies against EGFR and inhibitors of the EGFR tyrosine kinase. This review describes presently approved agents cetuximab (monoclonal EGFR antibody), gefitinib and erlotinib (EGFR tyrosine kinase inhibitors) in detail. Efficacy data for these agents in various human malignancies is presented. Various other agents that are in the early stages of development at present have also been mentioned.

Administration, Oral↗
PubMed2005

Follicular lymphoma: expanding therapeutic options.

The most common indolent lymphoma, follicular lymphoma comprises 35% of adult non-Hodgkin's lymphoma (NHL) in the United States and 22% worldwide. Features associated with adverse outcome include age, male gender, disease stage, and performance status, with the International Prognostic Index being the most widely used risk classification system. Long-term disease-free survival is possible in select patient subgroups after treatment, but very late relapses suggest that quiescent lymphoma cells might be harbored for long periods of time. Radiation therapy is the mainstay of treatment for limited-stage follicular lymphoma, but there is some experience with chemotherapy and combined chemoradiation. When to initiate treatment in patients with advanced disease is controversial, but options include various combined chemotherapy regimens, monoclonal antibodies, radiolabeled antibodies, and bone marrow or stem cell transplantation. Future directions in the treatment of follicular lymphoma include vaccines, antisense therapy, and proteasome inhibitors.

Antibodies, Monoclonal↗
PubMed2004

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↗
PubMed2003

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↗
PubMed2003

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↗
PubMed2003

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↗
PubMed2003

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↗
PubMed2003

Endothelium and the lipid metabolism: the current understanding.

The endothelium is a dynamic organ and responds to various physical and humoral conditions. The endothelium secretes several biologically active substances, both vasoconstrictors and vasodilators, which control these processes. Endothelial function is most commonly assessed as the vasodilatory response to stimuli. Several endothelium-dependent agonists have been identified, each of which acts through a membrane receptor. Nitric oxide which is continuously synthesized by the endothelium has a wide range of biological properties that maintain vascular homeostasis. It is a potent vasodilator and inhibitor of platelet aggregation and thus has an important protective role. Endothelial dysfunction in hypercholesterolemic patients is in large part due to a reduced bioavailability of NO. Traditional coronary risk factors, especially hypercholesterolemia, produce endothelial dysfunction even in patients with normal blood vessels. The underlying mechanisms involve a local inflammatory response, release of cytokines and growth factors, activation of oxidation-sensitive mechanisms in the arterial wall, modulation of intracellular signaling pathways, increased oxidation of low-density lipoprotein cholesterol, and quenching of nitric oxide. Clinical studies have shown a significant improvement in endothelial dysfunction following lowering of serum cholesterol levels, infusion of nitric oxide donors like L-arginine and exercise training. Clinical trials are underway examining the role of endothelin-1 receptor antagonists like bosentan in the prevention of graft atherosclerosis.

Cardiovascular Diseases↗
PubMed2003

HER-2/neu overexpression detected by immunohistochemistry in soft tissue sarcomas.

Sarcomas currently represent 1% of adult malignancies and 15% of pediatric malignancies. To determine the prevalence of HER-2/neu overexpression by the histologic type and to identify a possible predictive role in patients with sarcoma, we performed a retrospective study on subjects with a biopsy-proven diagnosis of a soft tissue sarcoma. HER-2/neu overexpression was evaluated using immunohistochemistry (IHC) performed on paraffin-embedded specimens. An IHC score of 2+ or greater was considered positive for overexpression. Two hundred seventy-three patients with soft tissue sarcoma were identified (164 females, 109 males) with a mean age of 56 (range: 1-93). The most common tumors identified were malignant fibrous histiocytoma (MFH) (18.3%), dermatofibrosarcoma (DFS) (16.1%), leiomyosarcoma (13.2%) and carcinosarcomas (CS) (7.3%). Of the 273 specimens, 29 (10.6%) revealed HER-2/neu overexpression. CS, MFH, and DFS specimens showed the highest incidence of HER-2/neu overexpression (40%, 26%, and 18.2%, respectively). The incidence of HER-2/neu overexpression was found to be significantly higher in patients with a survival of less than 8 months (p = 0.035). This demonstrates that HER-2/neu overexpression is preferentially seen in certain soft tissue sarcomas, and when present is associated with a poorer prognosis in patients with sarcoma. Further studies would delineate whether HER-2/neu overexpression renders sarcomas chemoresistant and thus adversely affects outcome. In addition, there may be a role for Herceptin (trastuzumab) alone, or in combination with conventional therapy, in patients with CS, MHF, and DFS.

Adolescent↗