IU Indianapolis ScholarWorks :: Browsing by Author "Masterson, Timothy A."

Browsing by Author "Masterson, Timothy A."

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Advances in Robotic-Assisted Radical Prostatectomy over Time
(Hindawi, 2013) Jacobs, Emma F. P.; Boris, Ronald; Masterson, Timothy A.; Urology, School of Medicine
Since the introduction of robot-assisted radical prostatectomy (RALP), robotics has become increasingly more commonplace in the armamentarium of the urologic surgeon. Robotic utilization has exploded across surgical disciplines well beyond the fields of urology and prostate surgery. The literature detailing technical steps, comparison of large surgical series, and even robotically focused randomized control trials are available for review. RALP, the first robot-assisted surgical procedure to achieve widespread use, has recently become the primary approach for the surgical management of localized prostate cancer. As a result, surgeons are constantly trying to refine and improve upon current technical aspects of the operation. Recent areas of published modifications include bladder neck anastomosis and reconstruction, bladder drainage, nerve sparing approaches and techniques, and perioperative and postoperative management including penile rehabilitation. In this review, we summarize recent advances in perioperative management and surgical technique for RALP.
Ambient ionization mass spectrometric analysis of human surgical specimens to distinguish renal cell carcinoma from healthy renal tissue
(Springer, 2016-08) Alfaro, Clint M.; Jarmusch, Alan K.; Pirro, Valentina; Kerian, Kevin S.; Masterson, Timothy A.; Cheng, Liang; Cooks, R. Graham; Urology, School of Medicine
Touch spray - mass spectrometry (TS-MS) is an ambient ionization technique (ionization of unprocessed samples in the open air) that may find intraoperative applications in quickly identifying the disease state of cancerous tissues and in defining surgical margins. In this study, TS-MS was performed on fresh kidney tissue (~1–5 cm3), within one hour of resection, from 21 human subjects afflicted by renal cell carcinoma (RCC). The preliminary diagnostic value of TS-MS data taken from freshly resected tissue was evaluated. Principal component analysis (PCA) of the negative ion mode (m/z 700–1000) data provided separation between RCC (16 samples) and healthy renal tissue (13 samples). Linear discriminant analysis (LDA) on the PCA compressed data estimated sensitivity (true positive rate) and specificity (true negative rate) of 98% and 95%, respectively, based on histopathological evaluation. The results indicate that TS-MS might provide rapid diagnostic information in spite of the complexity of unprocessed kidney tissue and the presence of interferences such as urine and blood. Desorption electrospray ionization imaging (DESI-MSI) in the negative ionization mode was performed on the tissue specimens after TS-MS analysis as a reference method. The DESI imaging experiments provided phospholipid profiles (m/z 700–1000) that also separated RCC and healthy tissue in the PCA space, with PCA-LDA sensitivity and specificity of 100% and 89%, respectively. The TS and DESI loading plots indicated that different ions contributed most to the separation of RCC from healthy renal tissue (m/z 794 [PC 34:1+Cl]− and 844 [PC 38:4+Cl]− for TS vs. m/z 788 [PS 36:1-H]− and 810 [PS 38:4-H]− for DESI), while m/z 885 ([PI 38:4-H]−) was important in both TS and DESI. The prospect, remaining hurdles, and future work required for translating TS-MS into a method of intraoperative tissue diagnosis is discussed.,
The changing reality of urothelial bladder cancer: should non-squamous variant histology be managed as a distinct clinical entity?
(Wiley, 2015-08) Monn, M. Francesca; Kaimakliotis, Hristos Z.; Cary, K. Clint; Bihrle, Richard; Pedrosa, Jose A.; Masterson, Timothy A.; Foster, Richard S.; Gardner, Thomas A.; Cheng, Liang; Koch, Michael O.; Department of Urology, IU School of Medicine
Objectives To assess the effect of non-squamous differentiation (non-SQD) variant histology on survival in muscle-invasive bladder urothelial cancer (UC). Patients and Methods A cohort of 411 radical cystectomy (RC) cases performed with curative intent for muscle-invasive primary UC was identified between 2008 and June 2013. Survival analysis was evaluated using Kaplan–Meier methodology comparing non-variant (NV) + SQD histology to non-SQD variant histology (non-SQD variants). Multivariable cox proportional hazards regression assessed all-cause and disease-specific mortality. Results Of the 411 RC cases, 77 (19%) had non-SQD variant histology. The median overall survival (OS) for non-SQD variant histology was 28 months, whereas the NV+SQD group had not reached the median OS at 74 months (log-rank test P < 0.001). After adjusting for sex, age, pathological stage, and any systemic chemotherapy, patients with non-SQD variant histology at RC had a 1.57-times increased adjusted risk of all-cause mortality (P = 0.027) and 1.69-times increased risk of disease-specific mortality (P = 0.030) compared with NV+SQD patients. Conclusions While SQD behaves similarly to NV, non-SQD variant histology portends worse OS and disease-specific survival regardless of neoadjuvant or adjuvant chemotherapy and pathological stage. Non-SQD variants of UC could perhaps be considered a distinct clinical entity in UC with goals for developing new treatment algorithms through novel clinical trials.
Cholesteryl Ester Accumulation Induced by PTEN Loss and PI3K/AKT Activation Underlies Human Prostate Cancer Aggressiveness
(Elsevier, 2014-03-04) Yue, Shuhua; Li, Junjie; Lee, Seung-Young; Lee, Hyeon Jeong; Shao, Tian; Song, Bing; Cheng, Liang; Masterson, Timothy A.; Liu, Xiaoqi; Ratliff, Timothy L.; Cheng, Ji-Xin; Department of Pathology & Laboratory Medicine, IU School of Medicine
Altered lipid metabolism is increasingly recognized as a signature of cancer cells. Enabled by label-free Raman spectromicroscopy, we performed quantitative analysis of lipogenesis at single cell level in human patient cancerous tissues. Our imaging data revealed an unexpected, aberrant accumulation of esterified cholesterol in lipid droplets of high-grade prostate cancer and metastases. Biochemical study showed that such cholesteryl ester accumulation was a consequence of loss of tumor suppressor PTEN and subsequent activation of PI3K/AKT pathway in prostate cancer cells. Furthermore, we found that such accumulation arose from significantly enhanced uptake of exogenous lipoproteins and required cholesterol esterification. Depletion of cholesteryl ester storage significantly reduced cancer proliferation, impaired cancer invasion capability, and suppressed tumor growth in mouse xenograft models with negligible toxicity. These findings open opportunities for diagnosing and treating prostate cancer by targeting the altered cholesterol metabolism.
Contemporary trends in postchemotherapy retroperitoneal lymph node dissection: Additional procedures and perioperative complications
(Elsevier, 2015-09) Cary, Clint; Masterson, Timothy A.; Bihrle, Richard; Foster, Richard S.; Department of Urology, IU School of Medicine
Introduction Postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) is a mainstay in the treatment of men with metastatic testicular cancer. We sought to determine whether trends in the need for additional intraoperative procedures and development of perioperative complications have changed over time. Methods Patients undergoing PC-RPLND from 2003 to 2011 were identified in the Indiana University Testis Cancer Database. Trends in the incidence of perioperative complications and additional procedures were assessed over time using regression tests of trend. Complications were classified according to the modified Clavien system. Univariable and multivariable logistic regression was used to determine factors associated with undergoing additional procedures. Results After exclusion criteria, 755 patients were included in the final study cohort. The incidence of additional procedures at PC-RPLND was 22.1% (167 of 755). The rate of additional procedures per year ranged from 17% to 30%, with no significant trend in any direction (Ptrend = 0.66). After adjusting for covariates, preoperative retroperitoneal (RP) mass size, elevated markers, and RP pathology remained significantly associated with the odds of an additional procedure. RP mass size of>10 cm was the strongest predictor (odds ratio = 7.2, 95% CI: 2.6–19.5). Overall, the incidence of perioperative complications was 3.7% (28 of 755). The rate of perioperative complications per year ranged from 0% to 7.3% with no significant trend in any direction (Ptrend = 0.06). Conclusion The incidence of perioperative complications is low with no significant trend over the last decade. A substantial number of patients require additional intraoperative procedures during PC-RPLND, which has remained stable at our institution over time.
Delaying Cancer Cases in Urology during COVID-19: Review of the Literature
(Wolters Kluwer, 2020-05-28) Tachibana, Isamu; Ferguson, Ethan L.; Mahenthiran, Ashorne; Natarajan, Jay P.; Masterson, Timothy A.; Bahler, Clinton D.; Sundaram, Chandru P.; Urology, School of Medicine
Purpose: Coronavirus Disease 2019 (COVID-19) is a global pandemic affecting hospital systems and the availability of resources for surgical procedures. Our aim is to provide guidance for urologists to help prioritize urologic cancer surgeries. Material and Methods: We reviewed published literature on bladder cancer, upper tract urothelial carcinoma (UTUC), penile cancer, testis cancer, prostate cancer, renal cancer, and adrenal cancer. Results: For muscle invasive bladder cancer (MIBC), delays should be less than roughly 10 weeks and neoadjuvant chemotherapy should be considered. For non-MIBC, patients should be counseled appropriately based on risk and intravesical therapies can continue. UTUC should also be treated with minimal delays for high risk patients, especially with ureteral tumors. Surgery for T1 renal cancers when indicated can be delayed until adequate resources are available. Patients with T2 renal cancer should be considered for early surgery if there are unfavorable pre-operative characteristics. Higher stage renal tumors should be considered for early surgery. Early multi-disciplinary approach is recommended for metastatic renal cancers. High risk prostate cancer may need preferential treatment and consideration of neoadjuvant hormonal therapy. Penile cancer can have worse sexual or oncologic outcome with prolonged surgical delay. Likewise, adrenal cancer is aggressive and needs early surgical treatment. Testicular cancer should be treated in a timely manner with surgery or chemotherapy, as indicated. Conclusions: This review should further assist urologists in recognizing patients with potentially aggressive tumor biology that warrant early treatment.
Distinctive Glycerophospholipid Profiles of Human Seminoma and Adjacent Normal Tissues by Desorption Electrospray Ionization Imaging Mass Spectrometry
(American Chemical Society, 2011) Masterson, Timothy A.; Dill, Allison L.; Eberlin, Livia S.; Mattarozzi, Monica; Cheng, Liang; Beck, Stephen D. W.; Bianchi, Federica; Cooks, R. Graham; Urology, School of Medicine
Desorption electrospray ionization mass spectrometry (DESI-MS) has been successfully used to discriminate between normal and cancerous human tissue from different anatomical sites. On the basis of this, DESI-MS imaging was used to characterize human seminoma and adjacent normal tissue. Seminoma and adjacent normal paired human tissue sections (40 tissues) from 15 patients undergoing radical orchiectomy were flash frozen in liquid nitrogen and sectioned to 15 μm thickness and thaw mounted to glass slides. The entire sample was two-dimensionally analyzed by the charged solvent spray to form a molecular image of the biological tissue. DESI-MS images were compared with formalin-fixed, hematoxylin and eosin (H&E) stained slides of the same material. Increased signal intensity was detected for two seminolipids [seminolipid (16:0/16:0) and seminolipid (30:0)] in the normal tubule testis tissue; these compounds were undetectable in seminoma tissue, as well as from the surrounding fat, muscle, and blood vessels. A glycerophosphoinositol [PI(18:0/20:4)] was also found at increased intensity in the normal testes tubule tissue when compared with seminoma tissue. Ascorbic acid (i.e., vitamin C) was found at increased amounts in seminoma tissue when compared with normal tissue. DESI-MS analysis was successfully used to visualize the location of several types of molecules across human seminoma and normal tissues. Discrimination between seminoma and adjacent normal testes tubules was achieved on the basis of the spatial distributions and varying intensities of particular lipid species as well as ascorbic acid. The increased presence of ascorbic acid within seminoma compared with normal seminiferous tubules was previously unknown.
Evidence of a dual histogenetic pathway of sacrococcygeal teratomas
(Wiley, 2017-01) Emerson, Robert E.; Kao, Chia-Sui; Eble, John N.; Grignon, David J.; Wang, Mingsheng; Zhang, Shaobo; Wang, Xiaoyan; Fan, Rong; Masterson, Timothy A.; Roth, Lawrence M.; Cheng, Liang; Department of Pathology and Laboratory Medicine, IU School of Medicine
Aims Sacrococcygeal teratomas are rare tumours that occur most frequently in neonates, although adult cases also occur. The molecular pathogenesis of these tumours and their long-term prognosis is uncertain. We investigated the i(12p) status of a large number of primary sacrococcygeal teratomas in both children and adults, including cases with malignant germ cell tumour elements. Methods and results Fifty-four sacrococcygeal teratoma specimens from 52 patients were identified, and available follow-up information was obtained. Fluorescence in-situ hybridization analysis was performed to identify isochromosome 12p [i(12p)] abnormalities on paraffin blocks of the tumours. Among the 48 paediatric patients, there were 44 teratomas and four tumours with combined teratoma and yolk sac tumour (one of whom also had primitive neuroectodermal tumour). The teratomas included 37 mature teratomas and 11 immature teratomas (four grade 1, two grade 2, and five grade 3). The 44 teratomas lacking a yolk sac tumour component were all negative for i(12p). The four tumours with a yolk sac tumour component were all positive for i(12p). The four adult cases all lacked non-teratomatous germ cell tumour components, immature elements, and i(12p). Follow-up information was available for 32 patients. Two patients with teratoma had recurrence, but were alive with no evidence of disease after long-term follow-up. One patient with combined teratoma and yolk sac tumour had recurrence 7 months after resection. The other patients were alive with no evidence of disease at last follow-up. Conclusions Our data suggest that paediatric sacrococcygeal teratomas should be considered as two distinct groups with divergent histogenetic pathways. The prognosis of these tumours is excellent, despite rare recurrence.
Long-Term Survival of Good-Risk Germ Cell Tumor Patients After Postchemotherapy Retroperitoneal Lymph Node Dissection: A Comparison of BEP × 3 vs. EP × 4 and Treating Institution
(Elsevier, 2017) Cary, Clint; Jacob, Joseph M.; Albany, Costantine; Masterson, Timothy A.; Hanna, Nasser H.; Einhorn, Lawrence H.; Foster, Richard S.; Urology, School of Medicine
Background Patients with International Germ Cell Cancer Collaborative Group (IGCCCG) good-risk testicular cancer might receive either 4 cycles of etoposide and cisplatin (EP × 4) or 3 cycles of bleomycin, etoposide, and cisplatin (BEP × 3). We sought to examine differences in survival after retroperitoneal lymph node dissection (PC-RPLND) between patients who received EP × 4 compared with BEP × 3. Patients and Methods The Indiana University Testis Cancer database was queried to identify IGCCCG good-risk PC-RPLND patients who received either EP × 4 or BEP × 3 induction chemotherapy. The primary outcome was overall survival (OS). Kaplan–Meier plots were generated for the EP × 4 and BEP × 3 groups and compared using the log rank test. Cox regression analysis was used to determine risk of mortality. Results A total of 223 patients met inclusion criteria between 1985 and 2011. Induction chemotherapy consisted of EP × 4 in 45 (20%) patients and BEP × 3 in 178 (80%). Most patients (78%) received their chemotherapy at outside institutions and were subsequently referred for PC-RPLND. The location of treating institution did not influence outcomes significantly when similar chemotherapy regimens were compared in this good-risk cohort. The 10-year OS for the EP × 4 and BEP × 3 groups were 91% and 98%, respectively (log rank P < .01). The adjusted risk of death in the EP × 4 group showed a nonsignificant trend of 3 times greater compared with the BEP × 3 group (hazard ratio, 3.1; 95% confidence interval, 0.8-12.0; P = .10). Conclusion The regimen of BEP × 3 resulted in a trend toward improved survival, however, this did not reach statistical significance. The location of treating institution seems less important in this risk group of patients.
Multivariate statistical differentiation of renal cell carcinomas based on lipidomic analysis by ambient ionization imaging mass spectrometry
(Springer, 2010) Dill, Allison L.; Eberlin, Livia S.; Zheng, Cheng; Costa, Anthony B.; Ifa, Demian R.; Cheng, Liang; Masterson, Timothy A.; Koch, Michael O.; Vitek, Olga; Cooks, R. Graham; Pathology and Laboratory Medicine, School of Medicine
Desorption electrospray ionization (DESI) mass spectrometry (MS) was used in an imaging mode to interrogate the lipid profiles of thin tissue sections of 11 sample pairs of human papillary renal cell carcinoma (RCC) and adjacent normal tissue and nine sample pairs of clear cell RCC and adjacent normal tissue. DESI-MS images showing the spatial distributions of particular glycerophospholipids (GPs) and free fatty acids in the negative ion mode were compared to serial tissue sections stained with hematoxylin and eosin (H&E). Increased absolute intensities as well as changes in relative abundance were seen for particular compounds in the tumor regions of the samples. Multivariate statistical analysis using orthogonal projection to latent structures treated partial least square discriminate analysis (PLS-DA) was used for visualization and classification of the tissue pairs using the full mass spectra as predictors. PLS-DA successfully distinguished tumor from normal tissue for both papillary and clear cell RCC with misclassification rates obtained from the validation set of 14.3% and 7.8%, respectively. It was also used to distinguish papillary and clear cell RCC from each other and from the combined normal tissues with a reasonable misclassification rate of 23%, as determined from the validation set. Overall DESI-MS imaging combined with multivariate statistical analysis shows promise as a molecular pathology technique for diagnosing cancerous and normal tissue on the basis of GP profiles.

Browsing by Author "Masterson, Timothy A."

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