Murugesan Manoharan

University of Miami Miller School of Medicine, Miami, Florida, United States

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Publications (169)514.78 Total impact

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    ABSTRACT: Neoadjuvant radiotherapy (NART) for muscle-invasive bladder cancer (MIBC) is currently underused. However, the outcomes for MIBC have remained suboptimal. We investigated the relationship of NART to cause-specific mortality (CSM) and overall mortality (OM) among patients with a diagnosis of MIBC. The patients diagnosed with primary invasive urothelial carcinoma of the bladder from 1983 to 2008 with localized disease were included. Patients aged > 90 years, those diagnosed with T1 or T4 BC, and those with no information on tumor grade were excluded from the analysis. Kaplan-Meier, Cox regression, and competing risk methods were used in the analysis of OM and CSM. A total of 5562 patients were included in the cohort (115 NART and 5447 surgery alone). On univariate analysis, NART significantly decreased the OM for patients with high-grade BC (hazard ratio [HR], 0.8), stage T2b (HR, 0.74), and stage T2b/T3 (HR, 0.74). CSM was also lower for those with stage T2b disease (HR, 0.63). Multivariable analysis revealed that NART was associated with a significant decrease in CSM (P = .043) and OM (P = .0462) for those with T2b. Likewise, an improvement was seen in OM (P = .0337) for patients with T2b/T3 who had received NART. NART was significantly associated with decreased CSM and OM in patients with clinical T2b/T3 BC and OM for patients with T2b/T3. These data suggest that NART could be beneficial in patients with T2b/T3 BC. In the modern era, the greatest utility would potentially be for patients with an incomplete response to neoadjuvant chemotherapy or as an adjunct to chemotherapy to improve the complete response rates. Copyright © 2015 Elsevier Inc. All rights reserved.
    Clinical Genitourinary Cancer 03/2015; DOI:10.1016/j.clgc.2015.02.014 · 1.69 Impact Factor
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    ABSTRACT: Hypercalcemia of malignancy is a common finding associated with different types of cancers; however, its association with urothelial carcinoma of the bladder is rare. We report a case of a 69-year-old male with nonmetastatic urothelial carcinoma of the bladder who developed hypercalcemia that failed to respond to medical management, but resolved completely after undergoing resection of the tumor through radical cystectomy.
    Urology Annals 01/2015; 7(1):86-7. DOI:10.4103/0974-7796.148627
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    Ahmed Ali, Sanjaya Swain, Murugesan Manoharan
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    ABSTRACT: Pelvic lipomatosis is a rare benign disease, associated with overgrowth of fat in the perivesical and perirectal area. It is of unknown etiology. We describe a 45-year-old male with pelvic lipomatosis causing bladder storage dysfunction symptoms and pelvic pain that affected his quality of life. Surgical excision of the pelvic mass with bladder preservation was performed. After surgery, the patient had a marked improvement in his quality of life, with resolution of bladder storage dysfunction symptoms and pelvic pain.
    08/2014; 67(3):287-8. DOI:10.5173/ceju.2014.03.art15
  • The Journal of Urology 04/2014; 191(4):e301-e302. DOI:10.1016/j.juro.2014.02.664 · 3.75 Impact Factor
  • The Journal of Urology 04/2014; 191(4):e310. DOI:10.1016/j.juro.2014.02.756 · 3.75 Impact Factor
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    ABSTRACT: Self-expanding stents are relatively new in the field of urology and have primarily been used for permanent remodeling of benign or malignant stricture. We are presenting a rare and interesting case of a ureterocolic fistula that formed secondary to placement of an expandable, retrievable metal stent in the ureter. After multiple retrieval efforts, the self-expanding metal stent was finally retrieved and a ureterocolic fistula was appreciated on antegrade pyelography. The patient chose to manage it non-surgically, with routine nephroureteral catheter exchanges, and her creatinine continues to remain stable.
    08/2013; 66(2):239-41. DOI:10.5173/ceju.2013.02.art33
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    ABSTRACT: OBJECTIVE: To validate and compare the accuracy and performance of nomograms predicting insignificant prostate cancer and to analyze their performance in patients with different cancer locations. METHODS: Our cohort consisted of 370 radical prostatectomy patients with Gleason ≤6 prostate cancer diagnosed on transrectal biopsy with at least 10 cores. We quantified the performance of each nomogram with respect to discrimination, calibration, predictive accuracy at different cut points, and the clinical net benefit. We also evaluated these parameters in subgroups of patients with predominantly anterior-apical (AA) and posterior-basal (PB) tumor location. RESULTS: Insignificant prostate cancer was present in 141 patients (38%). The Kattan and Steyerberg nomograms outperformed other studied models and demonstrated fair discrimination (areas under the receiver operating characteristics curve 0.768 and 0.770, respectively), good calibration, balanced predictive accuracy, and the highest net benefit. All nomograms were less accurate at higher levels of predicted probability. The performance of the nomograms was better in patients with PB tumors than in those with AA tumors. The loss of correlation with the actual prevalence of insignificant prostate cancer at higher levels of predicted probability was not seen in the PB subgroup but was particularly noticeable in the AA subgroup. CONCLUSION: The Kattan and Steyerberg nomograms demonstrated the best performance in predicting the probability of insignificant prostate cancer in a contemporary cohort of patients with Gleason ≤6 cancer diagnosed on specimens from an extended transrectal biopsy. However, all studied nomograms were more accurate in identifying significant rather than insignificant disease, particularly for tumors located in the apical and anterior prostate.
    Urology 04/2013; 81(6). DOI:10.1016/j.urology.2013.01.062 · 2.13 Impact Factor
  • The Journal of Urology 04/2013; 189(4):e380-e381. DOI:10.1016/j.juro.2013.02.503 · 3.75 Impact Factor
  • The Journal of Urology 04/2013; 189(4):e273-e274. DOI:10.1016/j.juro.2013.02.224 · 3.75 Impact Factor
  • The Journal of Urology 04/2013; 189(4):e547. DOI:10.1016/j.juro.2013.03.050 · 3.75 Impact Factor
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    ABSTRACT: Currently there is no global agreement as to how extensively a radical prostatectomy specimen should be sectioned and histologically examined. We analyzed the ability of different methods of partial sampling in detecting positive margin (PM) and extraprostatic extension (EPE)-2 pathologic features of prostate cancer that are most easily missed by partial sampling of the prostate. Radical prostatectomy specimens from 617 patients treated with open radical prostatectomy between 1992 and 2011 were analyzed. Examination of the entirely submitted prostate detected only PM in 370 (60%), only EPE in 100 (16%), and both in 147 (24%) specimens. We determined whether these pathologic features would have been diagnosed had the examination of the specimen been limited only to alternate sections (method 1), alternate sections representing the posterior aspect of the gland in addition to one of the mid-anterior aspects (method 2), and every section representing the posterior aspect of the gland in addition to one of the mid-anterior aspects, supplemented by the remaining ipsilateral anterior sections if a sizeable tumor is seen (method 3). Methods 1 and 2 missed 13% and 21% of PMs and 28% and 47% of EPEs, respectively. Method 3 demonstrated better results missing only 5% of PMs and 7% of EPEs. Partial sampling techniques missed slightly more PMs and EPEs in patients with low-risk to intermediate-risk prostate cancer, although even in high-risk cases none of the methods detected all of the studied aggressive pathologic features.
    The American journal of surgical pathology 10/2012; DOI:10.1097/PAS.0b013e318268ccc1 · 4.59 Impact Factor
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    ABSTRACT: Chemotherapy was shown to improve survival in patients undergoing radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC). The initiation and completion rates for perioperative chemotherapy are variable. Our aim is to compare the likelihood of initiating and completing neoadjuvant (NAC) and adjuvant chemotherapy (AC) in patients who underwent of RC for MIBC. We performed a retrospective analysis of patients who underwent RC between 1992 and 2011. NAC was advised for patients with clinical stage ≥T2, hydronephrosis, extensive lymphovascular invasion (LVI), or prostatic stromal invasion. Patients with ≥pT3 or lymph node metastases were considered for AC. A total of 363 patients were considered for perioperative chemotherapy. Among the 141 patients who were offered NAC, 125 (88.6%) initiated NAC. A total of 222 were considered for AC, and 151 (68.0%) initiated AC ( < 0.001). In the NAC group, 118 (83.5%) completed planned number of cycles of chemotherapy and 7 (5.6%) did not complete the planned chemotherapy. In the AC group, 79 (35.5%) completed at least four cycles and 72 (47.3%) could not complete the planned cycles ( < 0.001). Patients with MIBC are more likely to initiate and complete NAC than AC.
    Indian Journal of Urology 10/2012; 28(4):424-6. DOI:10.4103/0970-1591.105756
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    ABSTRACT: The purpose of our analysis was to determine if delays in treatment caused by active surveillance result in significant pathological changes when patients no longer meet the criteria on repeat biopsy and to study whether or not these changes may affect treatment outcomes. Out of 207 men who were on active surveillance, 47 (23%) no longer met the criteria after one of the repeat biopsies. Twenty-two underwent radical prostatectomy at our institution and formed the main group (Group 1) of this study. One hundred sixty-four patients met the criteria for active surveillance but underwent immediate surgery. Of these patients, we selected 38 (23%) with the lowest predicted biochemical recurrence-free survival. These patients formed the comparison group (Group 2). Pathological features as well as postoperative biochemical outcomes were compared between the groups. Seven patients (32%) in Group 1 and four (11%) in Group 2 have predominantly high-grade cancer (i.e., ≥4/5 + 3) at pathology. The visually estimated percent of carcinoma was also higher in patients initially managed by active surveillance (median 12.5 vs. 5.0 in Groups 1 and 2, respectively, P = 0.009). Other pathological characteristics were similar in both groups. With limited duration of follow-up, postoperative biochemical recurrence-free survival did not differ significantly between the groups. Our study has demonstrated that both tumor grade and volume may increase during active surveillance. However, the clinical significance of these changes with respect to the outcomes of delayed treatment remains to be established.
    The Prostate 10/2012; 72(14):1573-9. DOI:10.1002/pros.22507 · 3.57 Impact Factor
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    ABSTRACT: Adrenal tumors are among the commonest incidental findings discovered. The increased incidence of diagnosing adrenal incidentalomas is due to the widespread availability and use of noninvasive imaging studies. Extensive research has been conducted to define a cost-effective diagnostic and therapeutic protocol to guide physicians in managing incidental adrenal lesions. However, there is little consensus on the optimal management strategy. Published literature to date, describes a wide spectrum of treatment options ranging from excision of all adrenal lesions regardless of the size and functional status to extensive hormonal and radiological evaluation to avoid surgery. In this review, we present a comprehensive overview of the presentation, evaluation and management of adrenal incidentalomas. Additionally, we propose a management algorithm to optimally manage these tumors.
    Urology Annals 09/2012; 4(3):137-44. DOI:10.4103/0974-7796.102657
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    ABSTRACT: CONTEXT: A summary of the 2nd International Consultation on Bladder Cancer recommendations on the reconstructive options after radical cystectomy (RC), their outcomes, and their complications. OBJECTIVE: To review the literature regarding indications, surgical details, postoperative care, complications, functional outcomes, as well as quality-of-life measures of patients with different forms of urinary diversion (UD). EVIDENCE ACQUISITION: An English-language literature review of data published between 1970 and 2012 on patients with UD following RC for bladder cancer was undertaken. No randomized controlled studies comparing conduit diversion with neobladder or continent cutaneous diversion have been performed. Consequently, almost all studies used in this report are of level 3 evidence. Therefore, the recommendations given here are grade C only, meaning expert opinion delivered without a formal analysis. EVIDENCE SYNTHESIS: Indications and patient selection criteria have significantly changed over the past 2 decades. Renal function impairment is primarily caused by obstruction. Complications such as stone formation, urine outflow, and obstruction at any level must be recognized early and treated. In patients with orthotopic bladder substitution, daytime and nocturnal continence is achieved in 85-90% and 60-80%, respectively. Continence is inferior in elderly patients with orthotopic reconstruction. Urinary retention remains significant in female patients, ranging from 7% to 50%. CONCLUSIONS: RC and subsequent UD have been assessed as the most difficult surgical procedure in urology. Significant disparity on how the surgical complications were reported makes it impossible to compare postoperative morbidity results. Complications rates overall following RC and UD are significant, and when strict reporting criteria are incorporated, they are much higher than previously published. Fortunately, most complications are minor (Clavien grade 1 or 2). Complications can occur up to 20 yr after surgery, emphasizing the need for lifelong monitoring. Evidence suggests an association between surgical volume and outcome in RC; the challenge of optimum care for elderly patients with comorbidities is best mastered at high-volume hospitals by high-volume surgeons. Preoperative patient information, patient selection, surgical techniques, and careful postoperative follow-up are the cornerstones to achieve good long-term results.
    European Urology 08/2012; 63(1). DOI:10.1016/j.eururo.2012.08.050 · 12.48 Impact Factor
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    ABSTRACT: BACKGROUND: C-X-C chemokine receptor 4 (CXCR4) and CXCR7 are 7-transmembrane chemokine receptors of the stroma-derived factor (SDF-1). CXCR4, but not CXCR7, has been examined in bladder cancer (BCa). This study examined the functional and clinical significance of CXCR7 in BCa. METHODS: CXCR4 and CXCR7 levels were measured in BCa cell lines, tissues (normal = 25; BCa = 44), and urine specimens (n = 186) by quantitative polymerase chain reaction and/or immunohistochemistry. CXCR7 function in BCa cells were examined by transient transfections using a CXCR7 expression vector or small interfering RNA. RESULTS: In BCa cell lines, CXCR7 messenger RNA levels were 5- to 37-fold higher than those for CXCR4. Transient overexpression of CXCR7 in BCa cell lines promoted growth and chemotactic motility. CXCR7 colocalized and formed a functional complex with epidermal growth factor receptor, phosphoinositide 3-kinase/Akt, Erk, and src and induced their phosphorylation. CXCR7 also induced up-regulation of cyclin-D1 and bcl-2. Suppression of CXCR7 expression reversed these effects and induced apoptosis. CXCR7 messenger RNA levels and CXCR7 staining scores were significantly (5- to 10-fold) higher in BCa tissues than in normal tissues (P < .001). CXCR7 expression independently associated with metastasis (P = .019) and disease-specific mortality (P = .03). CXCR7 was highly expressed in endothelial cells in high-grade BCa tissues when compared to low-grade BCa and normal bladder. CXCR7 levels were elevated in exfoliated urothelial cells from high-grade BCa patients (P = .0001; 90% sensitivity; 75% specificity); CXCR4 levels were unaltered. CONCLUSIONS: CXCR7 promotes BCa cell proliferation and motility plausibly through epidermal growth factor receptor receptor and Akt signaling. CXCR7 expression is elevated in BCa tissues and exfoliated cells and is associated with high-grade and metastasis. Cancer 2012. © 2012 American Cancer Society.
    Cancer 06/2012; 119(1). DOI:10.1002/cncr.27661 · 4.90 Impact Factor
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    ABSTRACT: Study Type - Prognosis (inception cohort) Level of Evidence 2 What's known on the subject? and What does the study add? A significant proportion of patients diagnosed with prostate cancer do not require immediate treatment and could be managed by active surveillance, which usually includes serial measurements of prostate-specific antigen (PSA) levels and regular biopsies. The rate of rise in PSA levels, which could be calculated as PSA velocity or PSA doubling time, was previously suggested to be associated with the biological aggressiveness of prostate cancer. Although these parameters are obvious candidates for predicting tumour progression in active surveillance patients, earlier studies that examined this topic provided conflicting results. Our analysis showed that PSA velocity and PSA doubling time calculated at different time-points, by different methods, over different intervals, and in different sub-groups of active surveillance patients provide little if any prognostic information. Although we found some significant associations between PSA velocity and the risk of progression as determined by biopsy, the actual clinical significance of this association was small. Furthermore, PSA velocity did not add to the predictive accuracy of total PSA. OBJECTIVE: •  To study whether prostate-specific antigen (PSA) velocity (PSAV) and PSA doubling time (PSADT) are associated with biopsy progression in patients managed by active surveillance. PATIENTS AND METHODS: •  Our inclusion criteria for active surveillance are biopsy Gleason sum <7, two or fewer positive biopsy cores, ≤20% tumour present in any core, and clinical stage T1-T2a. Changes in any of these parameters during the follow-up that went beyond these limits are considered to be progression. •  This study included 250 patients who had at least one surveillance biopsy, an available PSA measured no earlier than 3 months before diagnosis, and at least one PSA measurement before each surveillance biopsy. •  We evaluated the association between PSA kinetics and progression at successive surveillance biopsies in different sub-groups of patients by calculating the area under the curve (AUC) as well as sensitivity and specificity of different thresholds. RESULTS: •  Over a median follow-up of 3.0 years, the disease of 64 (26%) patients progressed. •  PSADT was not associated with biopsy progression, whereas PSAV was only weakly associated with progression in certain sub-groups. •  However, incorporation of PSAV in models including total PSA resulted in a moderate increase in AUC only when the entire cohort was analysed. In other sub-groups the predictive accuracy of total PSA was not significantly improved by adding PSAV. CONCLUSIONS: •  Our findings confirm that PSA kinetics should not be used in decision-making in patients with low-risk prostate cancer managed by active surveillance. •  Regular surveillance biopsies should remain as the principal method of monitoring cancer progression in these men.
    BJU International 06/2012; DOI:10.1111/j.1464-410X.2012.11295.x · 3.13 Impact Factor
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    ABSTRACT: Gender, smoking history, patient age, and tumor size have been found to impact the likelihood of benign histology at the time of nephron-sparing surgery (NSS). Providing external validation of these variables and evaluating the relationship between body mass index (BMI) and tumor location on the likelihood of benign histology during NSS for T1 tumors were the objectives of this study. Data were analyzed for consecutive patients undergoing NSS for T1 disease. Central tumors either were completely encircled by renal parenchyma, descended below the cortico-medullary junction, or were in direct opposition to the collecting system, renal sinus, or the hilar structures. Categorical variables were evaluated with chi-square test, and continuous variables were analyzed with independent sample t test. Logistic regression identified independent predictors of final pathology. NSS was performed in 316 patients, of whom 79 (24 %) had benign tumors. Patients with benign tumors were more likely to be female, to have a lower BMI, and to have peripheral tumors. On multivariate analysis, female gender (hazard ratio, 3.97; 95 % CI, 2.92-4.53, p < 0.001), peripheral tumor location (hazard ratio, 2.27; 95 % CI, 1.73-3.21, p = 0.014), and lower BMI (hazard ratio, 1.5; 95 % CI, 1.12-1.94, p = 0.015) were independently associated with benign histopathology at the time of surgical resection. Prospectively identifying which T1 tumors are benign would have tremendous implications for the patient. Ours is the first study that has identified the impact of tumor location and BMI on the risk of benign histology. Additional studies are needed to corroborate these findings and incorporate these data into future nomograms.
    International Urology and Nephrology 06/2012; 44(5):1319-24. DOI:10.1007/s11255-012-0207-z · 1.29 Impact Factor
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    ABSTRACT: The objective of this report is to describe the oncologic outcomes of men with margin-positive prostate cancer who were managed expectantly following radical prostatectomy. Between January 1992 and January 2011, 2166 men underwent an open radical prostatectomy by a single surgeon. Of these patients, 1592 (74%) had complete data and met the inclusion criteria of negative lymph nodes and no history of neoadjuvant or adjuvant therapy. This cohort was dichotomized by the presence or absence of at least one positive surgical margin. Groups were compared for differences in recurrence-free and overall survival. In total, 507 (32%) of 1592 patients had at least one positive surgical margin. Clinical and pathological characteristics of these patients indicated more aggressive disease. The median follow up for biochemical recurrence and overall survival was 3.4 years and 7.7 years, respectively. Of those patients with a positive margin, 147 (29%) recurred, with estimated 5 and 10 year biochemical recurrence rates of 31% and 47%, respectively. Multivariate analysis demonstrated that the presence of a positive margin was associated with a 2.45-fold increased hazard of recurrence (p < 0.001). Despite initial observation, surgical margin status was not associated with a decrease in overall survival on both uni- (p = 0.684) and multivariate analyses (p = 0.177). Although a positive surgical margin is associated with an increased risk of biochemical recurrence, patients in our series were not at an increased risk of all-cause mortality.
    The Canadian Journal of Urology 06/2012; 19(3):6280-6. · 0.91 Impact Factor

Publication Stats

2k Citations
514.78 Total Impact Points

Institutions

  • 2003–2015
    • University of Miami Miller School of Medicine
      • • Department of Urology
      • • Sylvester Comprehensive Cancer Center
      Miami, Florida, United States
  • 2005–2012
    • University of Miami
      • • Department of Urology
      • • Miller School of Medicine
      كورال غيبلز، فلوريدا, Florida, United States