Murugesan Manoharan

University of Miami, كورال غيبلز، فلوريدا, Florida, United States

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Publications (181)583.24 Total impact

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    ABSTRACT: Background: Multiparametric MRI has emerged as a popular imaging modality to localize prostate cancer. Nevertheless, interpretation of MRI is subjective, with concerns for false positives, particularly in the transitional zone (TZ), where hyperplastic changes may be confused for suspicion of cancer. We analyzed a prospective cohort of men undergoing MRI-US fusion biopsy and compared cancer detection rate between lesions seen in the peripheral zone (PZ) and the TZ. Methods: 133 men with elevated PSA or positive DRE underwent MRI-US fusion biopsy with average of 2 cores taken per target for the detection of prostate cancer between October 2014 and July 2015. Each targeted lesion in the PZ and TZ was previously classified by radiologists according to the MRI PI-RADS score and grouped according to their level of suspicion as probably benign (1-2), indeterminate (3) or probably malignant (4-5). Histopathology from targeted cores were categorized as no cancer, non-significant cancer (Gleason 6) and significant cancer (Gleason ≥ 7). We compared the cancer detection rates between lesions in PZ and TZ lesions, based on PI-RADS score. Results: We identified 143 lesions in the PZ and 82 lesions in the TZ. Among lesions found in the TZ, 57.3% were reported as probably malignant, compared to 44.7% of lesions seen in the PZ. Cancer was diagnosed in 23% of the lesions in the PZ, compared to only in 9.7% in the TZ (p<0.01). With respect to significant cancer there was a trend towards higher detection of significant cancer in the PZ (13.29% vs. 6.10% p=0.12) compared to TZ. Furthermore, lesions in the PZ with a PI-RADS score > 4 were associated with a three-fold increase in the odds of detecting cancer compared to lesions with PI-RADS < 4 (OR 3.08; CI 95% 1.29 – 7.31, p<0.011), whereas in the TZ there was no increased risk of cancer with higher PI-RADS scores (OR 1.0 CI 95% 0.20 – 4.84, p<1.0). Conclusions: To our knowledge this is the first study to address a concern regarding an increased likelihood of false positives when reporting the presence and aggressiveness of cancer in the TZ versus the PZ. This may lead to unnecessary biopsies in men undergoing MRI of the prostate.
    No preview · Conference Paper · Mar 2016
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    ABSTRACT: Objective: To analyze the association between prediagnostic prostate-specific antigen kinetics and the risk of biopsy progression in prostate cancer patients on active surveillance, and to study the effect of prediagnostic prostate-specific antigen values on the predictive performance of prostate-specific antigen velocity and prostate-specific antigen doubling time. Methods: The study included 137 active surveillance patients with two or more prediagnostic prostate-specific antigen levels measured over a period of at least 3 months. Two sets of analyses were carried out. First, the association between prostate-specific antigen kinetics calculated using only the prediagnostic prostate-specific antigen values and the risk of biopsy progression was studied. Second, using the same cohort of patients, the predictive value of prostate-specific antigen kinetics calculated using only post-diagnostic prostate-specific antigens and compared with that of prostate-specific antigen kinetics based on both pre- and post-diagnostic prostate-specific antigen levels was analyzed. Results: Of 137 patients included in the analysis, 37 (27%) had biopsy progression over a median follow-up period of 3.2 years. Prediagnostic prostate-specific antigen velocity of more than 2 ng/mL/year and 3 ng/mL/year was statistically significantly associated with the risk of future biopsy progression. However, after adjustment for baseline prostate-specific antigen density, these associations were no longer significant. None of the tested prostate-specific antigen kinetics based on combined pre- and post-diagnostic prostate-specific antigen values were statistically significantly associated with the risk of biopsy progression. Conclusions: Historical prediagnostic prostate-specific antigens seems to be not clinically useful in patients diagnosed with low-risk prostate cancer on active surveillance.
    No preview · Article · Jan 2016 · International Journal of Urology
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    ABSTRACT: Purpose. The surgical expertise to perform robotic partial nephrectomy is heavily dependent on technology. The Da Vinci Xi (XI) is the latest robotic surgical platform with significant advancements compared to its predecessor. We describe our operative technique and experience with the XI system for robotic partial nephrectomy (RPN). Materials and Methods. Patients with clinical T1 renal masses were offered RPN with the XI. We used laser targeting, autopositioning, and a novel “in-line” port placement to perform RPN. Results. 15 patients underwent RPN with the XI. There were no intraoperative complications and no operative conversions. Mean console time was 101.3 minutes (range 44–176 minutes). Mean ischemia time was 17.5 minutes and estimated blood loss was 120 mLs. 12 of 15 patients had renal cell carcinoma. Two patients had oncocytoma and one had benign cystic disease. All patients had negative surgical margins and pathologic T1 disease. Two postoperative complications were encountered, including one patient who developed a pseudoaneurysm and one readmitted for presumed urinary tract infection. Conclusions. RPN with the XI system can be safely performed. Combining our surgical technique with the technological advancements on the XI offers patients acceptable pathologic and perioperative outcomes.
    No preview · Article · Jan 2016 · Advances in Urology
  • Alfredo Harb-De la Rosa · Matthew Acker · Raj A. Kumar · Murugesan Manoharan
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    ABSTRACT: Introduction: Bladder cancer is the sixth most common cancer in the Western world. Patients with bladder cancer require close monitoring, which may include frequent cystoscopy and urine cytology. Such monitoring results in significant health care cost. The application of epigenetics may allow for a risk adapted approach and more cost-effective method of monitoring. A number of epigenetic changes have been described for many cancer sites, including the urinary bladder. In this review, we discuss the use of epigenetics in bladder cancer and the potential diagnostic and therapeutic applications. Materials and methods: A comprehensive search of the English medical literature was conducted in PubMed using the terms microRNA regulation, DNA methylation, histone modification and bladder cancer. Results: The most important epigenetic changes include DNA methylation, histone modification and microRNA regulation. Both DNA hypomethylation and hypermethylation have been associated with higher rate of cancer. The association of epigenetic changes with bladder cancer has led to the research of its diagnostic and prognostic implications as well as to the development of novel drugs to target these changes with the aim of achieving a survival benefit. Conclusions: Recently, epigenetics has been shown to play a much greater role than previously anticipated in the initiation and propagation of many tumors. The use of epigenetics for the diagnosis and treatment of bladder cancer is an evolving and promising field. The possibility of reversing epigenetic changes may facilitate additional cancer treatment options in the future.
    No preview · Article · Oct 2015 · The Canadian Journal of Urology
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    Alfredo Harb-De la Rosa · Matthew Acker · Sanjaya Swain · Murugesan Manoharan
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    ABSTRACT: Renal cell carcinomas (RCC) are collectively the third most common type of genitourinary neoplasms, surpassed only by prostate and bladder cancer. Cure rates for renal cell carcinoma are related to tumor grade and stage; therefore, diagnostic methods for early detection and new therapeutic modalities are of paramount importance. Epigenetics can be defined as inherited modifications in gene expression that are not encoded in the DNA sequence itself. Epigenetics may play an important role in the pursuit of early diagnosis, accurate prognostication and identification of new therapeutic targets. We used PubMed to conduct a comprehensive search of the English medical literature using search terms including epigenetics, DNA methylation, histone modification, microRNA regulation (miRNA) and RCC. In this review, we discuss the potential application of epigenetics in the diagnosis, prognosis and treatment of kidney cancer. During the last decade, many different types of epigenetic alterations of DNA have been found to be associated with malignant renal tumors. This has led to the research of the diagnostic and prognostic implications of these changes in renal malignancies as well as to the development of novel drugs to target these changes, with the aim of achieving a survival benefit. Epigenetics has become a promising field in cancer research. The potential to achieve early detection and accurate prognostication in kidney cancer might be feasible through the application of epigenetics. The possibility to reverse these epigenetic changes with new therapeutic agents motivates researchers to continue pursuing better treatment options for kidney cancer and other malignancies.
    Preview · Article · Aug 2015 · Central European Journal of Urology
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    ABSTRACT: Robotic-assisted laparoscopic nephroureterectomy (RALNU) has been previously utilized for management of upper tract urothelial carcinoma. The da Vinci Xi surgical system was released in April of 2014. We describe our operative technique and early experience for RALNU using the da Vinci Xi system highlighting unique features of this surgical platform. A total of 10 patients with a diagnosis of upper tract urothelial carcinoma underwent RALNU using the da Vinci Xi system between April and November of 2014. A novel, oblique "in line" robotic trocar configuration was utilized to access the upper abdomen (nephrectomy portion) and pelvis (bladder cuff excision) without undocking. The port hopping feature of da Vinci Xi was utilized to facilitate optimal, multi-quadrant visualization during RALNU. Robotic-assisted laparoscopic nephroureterectomy was successfully completed without open conversion in all 10 patients. Mean operative time was 184 min (range 140-300 min), mean estimated blood loss was 121 cc (range 60-300 cc), and mean hospital stay was 2.4 days. Final pathology demonstrated high grade urothelial carcinoma in all patients. Surgical margins were negative in all patients. No intra-operative complications were encountered. One patient developed a pulmonary embolus after being discharged. No patients required a blood transfusion. Mean patient follow-up was 130 days (range 15-210 days). The use of da Vinci Xi with a novel, oblique "in line" port configuration and camera port hopping technique allows for an efficient and reproducible method for RALNU without the need for repositioning the patient or the robot during surgery.
    Preview · Article · Jun 2015 · SpringerPlus
  • Michael Garcia-Roig · David Pan · Devendar Katkoori · Murugesan Manoharan

    No preview · Article · Apr 2015 · The Journal of Urology
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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.
    No preview · Article · Mar 2015 · Clinical Genitourinary Cancer
  • Alfredo Harb-De La Rosa · Ahmed Ali · Sanjaya Swain · Murugesan Manoharan
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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.
    No preview · Article · Feb 2015 · Urology Annals
  • Murugesan Manoharan · Prashanth Kanagarajah
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    ABSTRACT: For the management purposes bladder cancer (BC) can be broadly divided into muscle invasive MIBC) and non-muscle invasive bladder cancer (NMIBC). NMIBC is mainly treated endoscopically while muscle invasive disease (MIBC) needs multimodal management including surgery, chemotherapy and radiotherapy in a multi-disciplinary set up. In cases where conservative measures have failed cystectomy may be the option in NMIBC while it remains one of the main options in MIBC. In selected cases it is possible to reconstruct urinary reservoir and even orthotopic bladder using segments of bowel.
    No preview · Chapter · Jan 2015
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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.
    Preview · Article · Aug 2014

  • No preview · Article · Apr 2014 · The Journal of Urology

  • No preview · Article · Apr 2014 · The Journal of Urology

  • No preview · Article · Oct 2013 · International Journal of Radiation OncologyBiologyPhysics
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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.
    Full-text · Article · Aug 2013 · Central European Journal of Urology
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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.
    Full-text · Article · Apr 2013 · Urology

  • No preview · Article · Apr 2013 · The Journal of Urology

  • No preview · Conference Paper · Apr 2013

  • No preview · Article · Apr 2013 · The Journal of Urology

  • No preview · Conference Paper · Apr 2013

Publication Stats

3k Citations
583.24 Total Impact Points

Institutions

  • 2005-2016
    • University of Miami
      • • Department of Urology
      • • Miller School of Medicine
      كورال غيبلز، فلوريدا, Florida, United States
  • 2003-2015
    • University of Miami Miller School of Medicine
      • Department of Urology
      Miami, Florida, United States
  • 2012
    • Comprehensive Cancer Centers of Nevada
      Las Vegas, Nevada, United States