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Item 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 MedicineObjectives 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.Item COEXISTING PROSTATE CANCER FOUND AT THE TIME OF HOLMIUM LASER ENUCLEATION OF THE PROSTATE FOR BENIGN PROSTATIC HYPERPLASIA: PREDICTING ITS PRESENCE AND GRADE IN ANALYZED TISSUE(Liebert, 2015-01) Bhojani, Naeem; Boris, Ronald S.; Monn, M. Francesca; Mandeville, Jessica A.; Lingeman, James E.; Department of Urology, IU School of MedicineObjective: To determine the incidence of prostate cancer identified on holmium laser enucleation of the prostate (HoLEP) specimens and evaluate variables associated with prostate cancer identification. Patients and Methods: All patients undergoing HoLEP between 1998 and 2013 were identified. Patients with a known history of prostate cancer were excluded. Multivariable logistic regression assessed variables associated with identification of prostate cancer on HoLEP specimens and Gleason 7 or higher prostate cancer among the malignant cases. The Gleason grade was used as a proxy for disease severity. Each of the models was adjusted for age, preoperative prostate-specific antigen (PSA), and HoLEP specimen weight. Results: The cohort comprised 1272 patients, of whom 103 (8.1%) had prostate cancer identified. Prostate cancer cases had higher pre-HoLEP PSA (p=0.06) but lower HoLEP specimen weight (p=0.01). On multivariate logistic regression, age and preoperative PSA were associated with increased odds of prostate cancer being present (p<0.01 each), while increasing HoLEP specimen weight was associated with decreased odds of prostate cancer (p<0.001). Men older than 80 had 20% predicted probability of being diagnosed with prostate cancer. Seventy-eight percent of prostate cancer cases were Gleason 6 or less. The pre-HoLEP PSA was associated with increased adjusted odds of intermediate- or high-grade prostate cancer. Conclusion: Prostate cancer identified by HoLEP is not uncommon, but is generally a low-risk disease. Older patients with smaller prostate glands have the highest odds of prostate cancer identification.Item 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 MedicineIntroduction 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.Item Correction to: Prognostic Features of Signal Transducer and Activator of Transcription 3 in an ER(+) Breast Cancer Model System(Libertas Academia, 2014-11) Liu, Li-Yu D.; Chang, Li-Yun; Kuo, Wen-Hung; Hwa, Hsiao-Lin; Lin, Yi-Shing; Jeng, Meei-Huey; Roth, Don A.; Chang, King-Jen; Hsieh, Fon-Jou; Department of Urology, IU School of MedicineItem Differentiation of Prostate Cancer from Normal Tissue in Radical Prostatectomy Specimens by Desorption Electrospray Ionization and Touch Spray Ionization Mass Spectrometry.(RSC, 2015-02-21) Kerian, K. S.; Jarmusch, A. K.; Pirro, V.; Koch, M. O.; Masterson, T. A.; Cheng, L.; Cooks, R. G.; Department of Urology, IU School of MedicineRadical prostatectomy is a common treatment option for prostate cancer before it has spread beyond the prostate. Examination for surgical margins is performed post-operatively with positive margins reported to occur in 6.5 – 32% of cases. Rapid identification of cancerous tissue during surgery could improve surgical resection. Desorption electrospray ionization (DESI) is an ambient ionization method which produces mass spectra dominated by lipid signals directly from prostate tissue. With the use of multivariate statistics, these mass spectra can be used to differentiate cancerous and normal tissue. The method was applied to 100 samples from 12 human patients to create a training set of MS data. The quality of the discrimination achieved was evaluated using principal component analysis - linear discriminant analysis (PCA-LDA) and confirmed by histopathology. Cross validation (PCA-LDA) showed >95% accuracy. An even faster and more convenient method, touch spray (TS) mass spectrometry, not previously tested to differentiate diseased tissue, was also evaluated by building a similar MS data base characteristic of tumor and normal tissue. An independent set of 70 non-targeted biopsies from six patients was then used to record lipid profile data resulting in 110 data points for an evaluation dataset for TS-MS. This method gave prediction success rates measured against histopathology of 93%. These results suggest that DESI and TS could be useful in differentiating tumor and normal prostate tissue at surgical margins and that these methods should be evaluated intra-operatively.Item Does Squamous Differentiation Portend Worse Outcomes in Urothelial Bladder Cancer?(Elsevier, 2015-11) Yang, David Y.; Monn, M. Francesca; Kaimakliotis, Hristos Z.; Cho, Jane S.; Cary, K. Clint; Pedrosa, Jose A.; Bihrle, Richard; Cheng, Liang; Koch, Michael O.; Department of Urology, IU School of MedicineIntroduction Interest on the impact of variant histology in bladder cancer prognosis is increasing. Although squamous differentiation is the most well characterized, only recently have less common variants gained increased recognition. We assessed whether squamous differentiation conferred a worse prognosis than nonvariant urothelial bladder cancer in a contemporary cohort of patients treated with radical cystectomy given the increased awareness of other less common variants. Methods We identified patients with squamous differentiation or nonvariant histology on transurethral resection of bladder tumor and/or cystectomy pathology during a 10-year period. Disease specific and overall survival were evaluated using Kaplan-Meier methodology. Cox regression was used to assess variables associated with mortality. Results Between 2003 and 2013, 934 patients underwent cystectomy for urothelial bladder cancer. Overall 617 nonvariant and 118 squamous differentiation cases were identified, and the remainder was nonsquamous differentiation variant histology. Overall 75% of patients with squamous differentiation had muscle invasive disease at diagnosis compared with 59% of those with nonvariant histology (p=0.002). Nonorgan confined disease at cystectomy was more common in patients with squamous differentiation (57% vs 44%, p=0.009). Among cases on neoadjuvant chemotherapy 20% (9 of 45) of nonvariant and 13% (1 of 8) of squamous differentiation were pT0N0 (p=0.527). Median followup was 52 months. Adjusted for demographics, pathological stage and chemotherapy, squamous differentiation was not associated with an increased risk of disease specific (HR 1.35, 95% CI 0.90–2.04, p=0.150) or all cause mortality (HR 0.90, 95% CI 0.60–1.25, p=0.515). Conclusions In a contemporary cohort of urothelial bladder cancer with recognition and characterization of less commonly described variants, squamous differentiation is not associated with a worse disease specific and all cause mortality when compared to a pure nonvariant cohort.Item A generic packaging technique using fluidic isolation for low-drift implantable pressure sensors(IEEE, 2015-06) Kim, Albert; Powell, Charles R.; Ziaie, Babak; Department of Urology, IU School of MedicineThis paper reports on a generic packaging method for reducing drift in implantable pressure sensors. The described technique uses fluidic isolation by encasing the pressure sensor in a liquid-filled medical-grade polyurethane balloon; thus, isolating it from surrounding aqueous environment that is the major source of baseline drift. In-vitro tests using commercial micromachined piezoresistive pressure sensors show an average baseline drift of 0.006 cmH2O/day (0.13 mmHg/month) for over 100 days of saline soak test, as compared to 0.101 cmH2O/day (2.23 mmHg/month) for a non-fluidic-isolated one soaked for 18 days. To our knowledge, this is the lowest reported drift for an implantable pressure sensor.Item Getting Out of a PCCL: Percutaneous Cholecystolithotomy as a Salvage Treatment Option for Gallstone Removal in Patients Deemed Unfit for Standard Surgical Approaches(Mary Ann Liebert, Inc., 2016-02-01) Calaway, Adam C.; Borofsky, Michael S.; Dauw, Casey A.; Lingeman, James E.; Department of Urology, IU School of MedicineDefinitive management of acute cholecystitis or symptomatic cholelithiasis in exceedingly high-risk patients remains a clinical dilemma. In certain cases, treatment through a percutaneous approach following standard techniques and principles similar to those of percutaneous nephrolithotomy may be considered. However, one potential challenge, particularly among a high-risk population, is the possible necessity to stay on obligate anticoagulation for pre-existing medical reasons. To date, there have been no prior reports documenting the role of this procedure in patients on systemic anticoagulation, particularly clopidogrel. Here we report a case of a percutaneous cholecystolithotomy performed on an elderly patient unable to stop dual antiplatelet therapy (aspirin and clopidogrel) secondary to recent drug eluting stent placement for myocardial infarction.Item Infection and venous thromboembolism in patients undergoing colorectal surgery: what is the relationship?(Ovid Technologies (Wolters Kluwer) - Lippincott Williams & Wilkins, 2014-04) Monn, M. Francesca; Hui, Xuan; Lau, Brandyn D.; Streiff, Michael; Haut, Elliott R.; Wick, Elizabeth C.; Efron, Jonathan E.; Gearhart, Susan L.; Department of Urology, IU School of MedicineBACKGROUND: There is evidence demonstrating an association between infection and venous thromboembolism. We recently identified this association in the postoperative setting; however, the temporal relationship between infection and venous thromboembolism is not well defined OBJECTIVE: We sought to determine the temporal relationship between venous thromboembolism and postoperative infectious complications in patients undergoing colorectal surgery. DESIGN, SETTING, AND PATIENTS: A retrospective cohort analysis was performed using data for patients undergoing colorectal surgery in the National Surgical Quality Improvement Project 2010 database. MAIN OUTCOME MEASURES: The primary outcome measures were the rate and timing of venous thromboembolism and postoperative infection among patients undergoing colorectal surgery during 30 postoperative days. RESULTS: Of 39,831 patients who underwent colorectal surgery, the overall rate of venous thromboembolism was 2.4% (n = 948); 729 (1.8%) patients were diagnosed with deep vein thrombosis, and 307 (0.77%) patients were diagnosed with pulmonary embolism. Eighty-eight (0.22%) patients were reported as developing both deep vein thrombosis and pulmonary embolism. Following colorectal surgery, the development of a urinary tract infection, pneumonia, organ space surgical site infection, or deep surgical site infection was associated with a significantly increased risk for venous thromboembolism. The majority (52%-85%) of venous thromboembolisms in this population occurred the same day or a median of 3.5 to 8 days following the diagnosis of infection. The approximate relative risk for developing any venous thromboembolism increased each day following the development of each type of infection (range, 0.40%-1.0%) in comparison with patients not developing an infection. LIMITATIONS: We are unable to account for differences in data collection, prophylaxis, and venous thromboembolism surveillance between hospitals in the database. Additionally, there is limited patient follow-up. CONCLUSIONS: These findings of a temporal association between infection and venous thromboembolism suggest a potential early indicator for using certain postoperative infectious complications as clinical warning signs that a patient is more likely to develop venous thromboembolism. Further studies into best practices for prevention are warranted.Item The learning curve and factors affecting warm ischemia time during robot-assisted partial nephrectomy(Wolters Kluwer, 2015-07) Dube, Hitesh; Bahler, Clinton D.; Sundaram, Chandru P.; Department of Urology, IU School of MedicineINTRODUCTION: The learning curve for robotic partial nephrectomy was investigated for an experienced laparoscopic surgeon and factors associated with warm ischemia time (WIT) were assessed. MATERIALS AND METHODS: Between 2007 and 2014, one surgeon completed 171 procedures. Operative time, blood loss, complications and ischemia time were examined to determine the learning curve. The learning curve was defined as the number of procedures needed to reach the targeted goal for WIT, which most recently was 20 min. Statistical analyses including multivariable regression analysis and matching were performed. RESULTS: Comparing the first 30 to the last 30 patients, mean ischemia time (23.0-15.2 min, P < 0.01) decreased while tumor size (2.4-3.4 cm, P = 0.02) and nephrometry score (5.9-7.0, P = 0.02) increased. Body mass index (P = 0.87), age (P = 0.38), complication rate (P = 0.16), operating time (P = 0.78) and estimated blood loss (P = 0.98) did not change. Decreases in ischemia time corresponded with revised goals in 2011 and early vascular unclamping with the omission of cortical renorrhaphy in selected patients. A multivariable analysis found nephrometry score, tumor diameter, cortical renorrhaphy and year of surgery to be significant predictors of WIT. CONCLUSIONS: Adoption of robotic assistance for a surgeon experienced with laparoscopic surgery was associated with low complication rates even during the initial cases of robot-assisted partial nephrectomy. Ischemia time decreased while no significant changes in blood loss, operating time or complications were seen. The largest decrease in ischemia time was associated with adopting evidence-based goals and new techniques, and was not felt to be related to a learning curve.