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Manish Kohli

Publications and source records attributed to Manish Kohli.

At least 19 recordsLinked to original sources
PubMed2006

Can computers improve patient care by primary health care workers in India?

OBJECTIVE: The objective was to test whether a decision support technology for non-physicians can increase health care utilization and quality. DESIGN: Before and after measurements were taken from a systematic random sample of patients and staff at randomly assigned intervention and control facilities. SETTING: The study took place at primary health facilities in rural Tamil Nadu, India. PARTICIPANTS: One thousand two hundred and eighty-six patients and 82 staff were interviewed. INTERVENTION: A computer-assisted decision support technology was introduced to assist with patient screening. MAIN OUTCOME MEASURES: Outcome measures included new patient visits per month, a Global Patient Assessment of Care Index, and health worker attitude variables. RESULTS: There was a difference of difference of 430 new patient visits per month at the intervention sites (P = 0.005), an increase from baseline of 18% at intervention sites compared with a decline of 5% at control sites. The intervention was associated with significant improvements in a Global Patient Assessment of Care Index (mean difference of difference 7.9, P < 0.001). The largest gains were made in patient communication, technical quality, and general satisfaction with care. The attitudes of public health workers toward the new technology and their jobs did not change. CONCLUSIONS: Decision support technologies have considerable potential to improve coverage and quality of health care for the poor and where there is no doctor, but the unreceptive attitude of public health workers would need to be overcome. Application of these technologies should take advantage of their popularity with patients and the opportunity to work through the private sector.

Attitude of Health Personnel↗
PubMed2006

Evaluation of prostate-specific antigen declines for surrogacy in patients treated on SWOG 99-16.

BACKGROUND: The identification of surrogate endpoints that can replace true outcome endpoints is crucial to the rapid evaluation of new cancer drugs. Retrospective analyses of phase II and III trials in metastatic androgen-independent prostate cancer have shown associations between declines in serum prostate-specific antigen (PSA) levels and survival. We evaluated PSA changes as potential surrogate markers for survival by using data from a clinical trial. METHODS: Men with androgen-independent prostate cancer were randomly assigned to either docetaxel/estramustine (D/E) or mitoxantrone/prednisone (M/P) treatment on Southwest Oncology Group Protocol 99-16. Of 674 eligible patients, 551 had a baseline PSA measurement and at least one PSA measurement during the first 3 months on protocol. PSA level declines of 5%-90% and PSA velocity at 1, 2, and 3 months were tested for surrogacy by using three statistical criteria: Prentice's criteria, the proportion of treatment effect explained, and the proportion of variation explained. All statistical tests were two-sided. RESULTS: Three-month PSA level declines of 20%-40%, a 2-month PSA decline of 30%, and PSA velocity at 2 and 3 months met all three surrogacy criteria. For example, a 3-month PSA decline of at least 30% was associated with a more than 50% decrease in the risk of death compared with the lack of such a decline (hazard ratio [HR] = 0.43, 95% confidence interval [CI] = 0.34 to 0.55; P < .001), and the increased risk of death for men treated with M/P compared with D/E (HR = 1.24, 95% CI = 1.02 to 1.51; P = .032) lost statistical significance after adjustment for this surrogate, whereas the decrease in risk of death associated with a 3-month 30% PSA decline remained statistically significant after adjustment for treatment. PSA level declines of 50%, commonly reported in clinical trials, did not meet the criteria for surrogacy. CONCLUSIONS: Several PSA measures satisfied the surrogacy criteria for survival in a retrospective analysis of data from SWOG 99-16. However, these measures await prospective validation in future clinical trials of chemotherapy in men with androgen-independent prostate cancer.

Aged↗
PubMed2006

Thrombin receptor expression is upregulated in prostate cancer.

BACKGROUND: Aberrant expression of protease-activated receptors (PARs) has been associated with increased angiogenesis, tumor growth, and metastasis of various cancers. We assessed the status of PAR1 expression in prostate cancer. METHODS: The study compared the abundance levels of PAR1 RNA and protein using real-time reverse-transcriptase polymerase chain reaction and immunoblotting in freshly resected prostate tissues from early localized-stage disease (n=9) to those from patients with advanced metastatic disease (n=7). PAR1 expression and localization was evaluated using immunohistochemical staining of prostate specimens with benign prostatic hyperplasia (n=27), early- (n=32) and advanced-stage (n=22) prostate cancer. Association analyses of PAR1 expression with expression of VEGF-family of growth factors, their receptors, and clinicopathological characteristics of the patients were also performed. RESULTS: PAR1 RNA expression in advanced-stage prostate was 2.39-fold higher (P=0.024) and its protein expression was 2.75-fold higher (P=5.89x10(-5)) when compared with early-stage prostate cancer. PAR1 expression was localized to endothelial cells in vascular network of prostate tumor areas. The expression of PAR1 correlated statistically significantly with advanced disease stage (P=0.0006) and pre-operative PSA levels (P=0.005) in these samples. CONCLUSIONS: These findings demonstrate that PAR1 expression is increased in prostate cancer. Its predominant expression in vascular network suggests that it may play a direct and crucial role in angiogenesis and could be a relevant target for therapeutic interventions to control or to prevent disease progression.

Adult↗
PubMed2006

Management of solitary palatal metastasis from renal cell carcinoma.

BACKGROUND: A 68-year-old male diagnosed with left-side renal cell carcinoma, and in clinical remission for 3 years following a nephrectomy, presented with a 2-month history of progressive difficulty in swallowing, accompanied by a new growth in the palate. Examination revealed a 25 mm x 25 mm soft-tissue growth at the junction of the hard and soft palate. Systemic examination did not reveal any other evidence of cancer progression. INVESTIGATIONS: CT scans, nasopharyngoscopy, fine-needle aspiration of palatal lesion and immunohistochemistry of biopsy specimen. DIAGNOSIS: Solitary palatal metastasis at the junction of the hard and soft palate from renal cell carcinoma. MANAGEMENT: Local, lesion-directed interferon therapy, repeat nasopharyngoscopy and regular clinical follow-up.

Aged↗
PubMed2006

Evaluation of an adrenal mass in a patient with progressive prostate cancer reveals pheochromocytoma.

Adrenal masses in cancer patients pose diagnostic problems. We report the case of a 59 years old male with a history of prostate cancer who presented to us with serially rising prostate specific antigen. On imaging studies he had bone lesions and in addition had a 1.7 cm left adrenal mass. Since metastasis to the adrenal gland has rarely been reported in prostate cancer, and since the radiological criteria in our case favored malignancy, we proceeded with hormonal evaluation and fine needle aspiration biopsy of the adrenal mass which proved it to be pheochromocytoma. This was followed by an uneventful adrenalectomy.

Adrenal Gland Neoplasms↗
PubMed2005

Stage-specific characterization of the vascular endothelial growth factor axis in prostate cancer: expression of lymphangiogenic markers is associated with advanced-stage disease.

PURPOSE: The vascular endothelial growth factor (VEGF) family plays a critical role in tumor angiogenesis and lymphangiogenesis. We characterized, at the mRNA and protein levels, the expression of VEGF-A and VEGF-D and their cognate receptors, VEGFR-1, VEGFR-2, and VEGFR-3 in early- and advanced-stage prostate cancer specimens. EXPERIMENTAL DESIGN: The levels of VEGF-A and VEGF-D mRNA in early- and advanced-stage specimens were compared using an angiogenic gene array and were confirmed by quantitative real-time PCR. Receptor protein levels and activation status were determined by immunoblotting. Spatial expression of the proteins was evaluated using immunohistochemistry with fresh and archival tissues from benign prostatic hypertrophy specimens, early-stage prostate specimens, and advanced-stage metastatic specimens. Circulating plasma levels of these growth factors were measured using ELISAs. RESULTS: We observed that expression patterns of VEGF isotypes corresponded to the prostate cancer stage: high expression of angiogenic growth factor VEGF-A was observed in early-stage prostate specimens, whereas high expression of lymphangiogenic growth factor VEGF-D was associated with advanced-stage metastatic disease. All VEGF receptors were present at variable levels in all specimens, but their activation states varied in a stage-specific manner. VEGFR-1 and, to a limited extent, VEGFR-2 were activated in early-stage specimens, whereas VEGFR-2 and VEGFR-3 were activated in advanced-stage specimens. CONCLUSIONS: Our results suggest that lymphangiogenic markers, such as VEGF-D and VEGFR-2 and VEGFR-3, may be better than angiogenic markers as targets of therapeutic intervention in advanced-stage prostate disease.

Adenocarcinoma↗
PubMed2005

Orbital metastasis from prostate cancer: an atypical case of neuroendocrine dedifferentiation during progression from hormone-sensitive to refractory stage.

We report a case of orbital metastasis from a neuroendocrine dedifferentiated prostate cancer during progression from hormone-sensitive to hormone refractory stage. A patient receiving androgen deprivation for hormone-sensitive prostate cancer presented with sudden-onset right-sided ptosis and an increasing serum prostate-specific antigen level. Imaging studies revealed a mixed blastic and lytic lesion involving the right orbital wall and the right cavernous sinus. Comparison of the metastatic histology with the original pathology confirmed a histologic change to poorly differentiated prostate adenocarcinoma with neuroendocrine features. Local radiation of the lesion and palliative systemic chemotherapy resulted in marked short-term improvement of all presenting symptoms. Because prostate cancer metastasis involves hematogenous and lymphatic routes, we also evaluated expression of the vascular endothelial growth factor (VEGF) and receptors (VEGFR-1, VEGFR-2, and VEGFR-3) in the metastatic deposit by immunohistochemistry. Strong expression of VEGFR-2 and VEGFR-3 restricted to the malignant epithelium was noted. We recommend a second biopsy of atypical prostate metastasis associated with sudden change to aggressive clinical behavior in order to evaluate for dedifferentiation features before planning appropriate treatment interventions especially in patients who are candidates for systemic chemotherapy.

Carcinoma, Neuroendocrine↗
PubMed2004

Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer.

BACKGROUND: Mitoxantrone-based chemotherapy palliates pain without extending survival in men with progressive androgen-independent prostate cancer. We compared docetaxel plus estramustine with mitoxantrone plus prednisone in men with metastatic, hormone-independent prostate cancer. METHODS: We randomly assigned 770 men to one of two treatments, each given in 21-day cycles: 280 mg of estramustine three times daily on days 1 through 5, 60 mg of docetaxel per square meter of body-surface area on day 2, and 60 mg of dexamethasone in three divided doses before docetaxel, or 12 mg of mitoxantrone per square meter on day 1 plus 5 mg of prednisone twice daily. The primary end point was overall survival; secondary end points were progression-free survival, objective response rates, and post-treatment declines of at least 50 percent in serum prostate-specific antigen (PSA) levels. RESULTS: Of 674 eligible patients, 338 were assigned to receive docetaxel and estramustine and 336 to receive mitoxantrone and prednisone. In an intention-to-treat analysis, the median overall survival was longer in the group given docetaxel and estramustine than in the group given mitoxantrone and prednisone (17.5 months vs. 15.6 months, P=0.02 by the log-rank test), and the corresponding hazard ratio for death was 0.80 (95 percent confidence interval, 0.67 to 0.97). The median time to progression was 6.3 months in the group given docetaxel and estramustine and 3.2 months in the group given mitoxantrone and prednisone (P<0.001 by the log-rank test). PSA declines of at least 50 percent occurred in 50 percent and 27 percent of patients, respectively (P<0.001), and objective tumor responses were observed in 17 percent and 11 percent of patients with bidimensionally measurable disease, respectively (P=0.30). Grade 3 or 4 neutropenic fevers (P=0.01), nausea and vomiting (P<0.001), and cardiovascular events (P=0.001) were more common among patients receiving docetaxel and estramustine than among those receiving mitoxantrone and prednisone. Pain relief was similar in both groups. CONCLUSIONS: The improvement in median survival of nearly two months with docetaxel and estramustine, as compared with mitoxantrone and prednisone, provides support for this approach in men with metastatic, androgen-independent prostate cancer.

Adenocarcinoma↗
PubMed2004

The academic hematology-oncology firm:a model for postgraduate cancer education.

OBJECTIVE: To examine whether the introduction of a subspecialty firm system results in improving fellowship training in hematology and oncology. METHODS: A subspecialty firm in Hematology-Oncology was created to provide ambulatory and inpatient, primary, and subspecialty care. A survey was conducted of all fellows who trained in this firm while enrolled in an affiliated University subspecialty fellowship program. RESULTS: The survey showed a positive impact of the firm in improving trainee-patient relationships, achievement of educational goals, and clinical competency. CONCLUSIONS: Larger observational studies are needed to evaluate the full impact of this model on educational outcomes in cancer patients.

Arkansas↗
PubMed2003

Role of coagulation and fibrinolytic system in prostate cancer.

Patients with prostate carcinoma paradoxically have both a hypercoagulable state and a bleeding diathesis. Hypercoagulability manifested by venous and arterial thrombosis has been documented in several large clinical trials. However, many investigators have reported a high risk of postoperative bleeding in prostate cancer patients. Disseminated intravascular coagulopathy has also been commonly noted at different clinical stages of this indolent cancer. In this article we review clinical, laboratory, and experimental evidence for abnormalities of various components of the coagulation and plasminogen pathways and analyze their contribution in prostate cancer growth, progression, and angiogenesis. Finally, we propose potential therapeutic antiangiogenic strategies in patients with prostate cancer.

Blood Coagulation↗