Browsing by Author "Bahler, Clinton D."
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Item [68Ga]Ga-P16-093 as a PSMA-Targeted PET Radiopharmaceutical for Detection of Cancer: Initial Evaluation and Comparison with [68Ga]Ga-PSMA-11 in Prostate Cancer Patients Presenting with Biochemical Recurrence(SpringerLink, 2020-06) Green, Mark A.; Hutchins, Gary D.; Bahler, Clinton D.; Tann, Mark; Mathias, Carla J.; Territo, Wendy; Sims, Justin; Polson, Heather; Alexoff, David; Eckelman, William C.; Kung, Hank F.; Fletcher, James W.; Radiology and Imaging Sciences, School of MedicinePurpose: This study was undertaken to evaluate radiation dosimetry for the prostate-specific membrane antigen targeted [68Ga]Ga-P16-093 radiopharmaceutical, and to initially assess agent performance in positron emission tomography (PET) detection of the site of disease in prostate cancer patients presenting with biochemical recurrence. Procedures: Under IND 133,222 and an IRB-approved research protocol, we evaluated the biodistribution and pharmacokinetics of [68Ga]Ga-P16-093 with serial PET imaging following intravenous administration to ten prostate cancer patients with biochemical recurrence. The recruited subjects were all patients in whom a recent [68Ga]Ga-PSMA-11 PET/X-ray computed tomography (CT) exam had been independently performed under IND 131,806 to assist in decision-making with regard to their clinical care. Voided urine was collected from each subject at ~ 60 min and ~ 140 min post-[68Ga]Ga-P16-093 injection and assayed for Ga-68 content. Following image segmentation to extract tissue time-activity curves and corresponding cumulated activity values, radiation dosimetry estimates were calculated using IDAC Dose 2.1. The prior [68Ga]Ga-PSMA-11 PET/CT exam (whole-body PET imaging at 60 min post-injection, performed with contrast-enhanced diagnostic CT) served as a reference scan for comparison to the [68Ga]Ga-P16-093 findings. Results: [68Ga]Ga-P16-093 PET images at 60 min post-injection provided diagnostic information that appeared equivalent to the subject's prior [68Ga]Ga-PSMA-11 scan. With both radiopharmaceuticals, sites of tumor recurrence were found in eight of the ten patients, identifying 16 lesions. The site of recurrence was not detected with either agent for the other two subjects. Bladder activity was consistently lower with [68Ga]Ga-P16-093 than [68Ga]Ga-PSMA-11. The kidneys, spleen, salivary glands, and liver receive the highest radiation exposure from [68Ga]Ga-P16-093, with estimated doses of 1.7 × 10-1, 6.7 × 10-2, 6.5 × 10-2, and 5.6 × 10-2 mGy/MBq, respectively. The corresponding effective dose from [68Ga]Ga-P16-093 is 2.3 × 10-2 mSv/MBq. Conclusions: [68Ga]Ga-P16-093 provided diagnostic information that appeared equivalent to [68Ga]Ga-PSMA-11 in this limited series of ten prostate cancer patients presenting with biochemical recurrence, with the kidneys found to be the critical organ. Diminished tracer appearance in the urine represents a potential advantage of [68Ga]Ga-P16-093 over [68Ga]Ga-PSMA-11 for detection of lesions in the pelvis.Item Comparison of tracer kinetic models for 68Ga-PSMA-11 PET in intermediate-risk primary prostate cancer patients(Springer, 2024-01-10) Smith, Nathaniel J.; Green, Mark A.; Bahler, Clinton D.; Tann, Mark; Territo, Wendy; Smith, Anne M.; Hutchins, Gary D.; Radiology and Imaging Sciences, School of MedicineBackground: 68Ga-PSMA-11 positron emission tomography enables the detection of primary, recurrent, and metastatic prostate cancer. Regional radiopharmaceutical uptake is generally evaluated in static images and quantified as standard uptake values (SUVs) for clinical decision-making. However, analysis of dynamic images characterizing both tracer uptake and pharmacokinetics may offer added insights into the underlying tissue pathophysiology. This study was undertaken to evaluate the suitability of various kinetic models for 68Ga-PSMA-11 PET analysis. Twenty-three lesions in 18 patients were included in a retrospective kinetic evaluation of 55-min dynamic 68Ga-PSMA-11 pre-prostatectomy PET scans from patients with biopsy-demonstrated intermediate- to high-risk prostate cancer. Three kinetic models-a reversible one-tissue compartment model, an irreversible two-tissue compartment model, and a reversible two-tissue compartment model, were evaluated for their goodness of fit to lesion and normal reference prostate time-activity curves. Kinetic parameters obtained through graphical analysis and tracer kinetic modeling techniques were compared for reference prostate tissue and lesion regions of interest. Results: Supported by goodness of fit and information loss criteria, the irreversible two-tissue compartment model optimally fit the time-activity curves. Lesions exhibited significant differences in kinetic rate constants (K1, k2, k3, Ki) and semiquantitative measures (SUV and %ID/kg) when compared with reference prostatic tissue. The two-tissue irreversible tracer kinetic model was consistently appropriate across prostatic zones. Conclusions: An irreversible tracer kinetic model is appropriate for dynamic analysis of 68Ga-PSMA-11 PET images. Kinetic parameters estimated by Patlak graphical analysis or full compartmental analysis can distinguish tumor from normal prostate tissue.Item Correcting the Shrinkage Effects of Formalin Fixation and Tissue Processing for Renal Tumors: toward Standardization of Pathological Reporting of Tumor Size(Ivyspring International Publisher, 2015-07-02) Tran, Thu; Sundaram, Chandru P.; Bahler, Clinton D.; Eble, John N.; Gringon, David J.; Monn, M. Francesca; Simper, Novae B.; Cheng, Liang; Department of Pathology and Laboratory Medicine, IU School of MedicineGiven the importance of correctly staging renal cell carcinomas, specific guidelines should be in place for tumor size measurement. While a standard means of renal tumor measurement has not been established, intuitively, tumor size should be based on fresh measurements. We sought to assess the accuracy of postfixation and microscopic measurements of renal tumor size, as compared to fresh measurements and radiographic size. Thirty-four nephrectomy cases performed by a single surgeon were prospectively measured at different time points. The study cases included 23 clear cell renal cell carcinomas, 6 papillary renal cell carcinomas, and 5 other renal tumors. Radiologic tumors were 12.1% larger in diameter than fresh tumors (P<0.01). Furthermore, fresh specimens were 4.6% larger than formalin-fixed specimens (P<0.01), and postfixation measurements were 7.1% greater than microscopic measurements (P<0.01). The overall mean percentage of shrinkage between fresh and histological specimens was 11.4% (P<0.01). Histological processing would cause a tumor stage shift from pT1b to pT1a for two tumors in this study. The shrinkage effects of formalin fixation and histological processing may result in understaging of renal cell carcinomas. The shrinkage factor should be considered when reporting tumor size.Item 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 MedicinePurpose: 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.Item Impact of positive surgical margins on overall survival after partial nephrectomy—A matched comparison based on the National Cancer Database(Elsevier, 2018-03) Shum, Cheuk Fan; Bahler, Clinton D.; Sundaram, Chandru P.; Urology, School of MedicineIntroduction The impact of positive surgical margins (PSM) in partial nephrectomy (PN) has been a controversy. Previous studies on the relationship between PSM and overall survival (OS) were either underpowered or had highly dissimilar groups. We used the National Cancer Database with propensity score matching to determine the association between PSM and OS after PN. Materials and methods We identified patients with T1/T2 N0M0 renal cancer treated with PN between 2004 and 2009, and divided them into 2 groups based on their margin status. We used propensity score matching to ensure similarities in age, comorbidity score (CCI), tumor size, histology, and grade between groups. Covariates were compared by χ2 test. Cox multiple regression was used to estimate the hazard ratios (HR) for all-cause mortality. OS between matched groups were compared by log-rank, Breslow and Tarone-Ware tests. Results After excluding those with missing data on margin or survival status, 20,762 patients were eligible for matching. Each matched group had 1,265 patients, similar in age, sex, race, CCI, tumor size, histology, and grade. There were 386 recorded all-cause mortalities over a median follow-up duration of 72.6 months. Cox multiple regression showed a higher risk of all-cause mortality among cases with PSM (HR: 1.393, P = 0.001). Old age, high CCI, and large tumors had higher risks, while papillary and chromophore histologic subtypes had lower risks. PSM was associated with significantly worse OS by log-rank, Breslow, and Tarone-Ware tests. Conclusion PSM is associated with significantly worse OS after PN.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.Item Management of Pain in Autosomal Dominant Polycystic Kidney Disease and Anatomy of Renal Innervation(Elsevier, 2015-05) Tellman, Matthew W.; Bahler, Clinton D.; Shumate, Ashley M.; Bacallao, Robert L.; Sundaram, Chandru P.; Department of Urology, IU School of MedicinePurpose Chronic pain is a prominent feature of autosomal dominant polycystic kidney disease that is difficult to treat and manage, often resulting in a decrease in quality of life. Understanding the underlying anatomy of renal innervation and the various etiologies of pain that occur in autosomal dominant polycystic kidney disease can help guide proper treatments to manage pain. Reviewing previously studied treatments for pain in autosomal dominant polycystic kidney disease can help characterize treatment in a stepwise fashion. Materials and Methods We performed a literature search of the etiology and management of pain in autosomal dominant polycystic kidney disease and the anatomy of renal innervation using PubMed® and Embase® from January 1985 to April 2014 with limitations to human studies and English language. Results Pain occurs in the majority of patients with autosomal dominant polycystic kidney disease due to renal, hepatic and mechanical origins. Patients may experience different types of pain which can make it difficult to clinically confirm its etiology. An anatomical and histological evaluation of the complex renal innervation helps in understanding the mechanisms that can lead to renal pain. Understanding the complex nature of renal innervation is essential for surgeons to perform renal denervation. The management of pain in autosomal dominant polycystic kidney disease should be approached in a stepwise fashion. Acute causes of renal pain must first be ruled out due to the high incidence in autosomal dominant polycystic kidney disease. For chronic pain, nonopioid analgesics and conservative interventions can be used first, before opioid analgesics are considered. If pain continues there are surgical interventions such as renal cyst decortication, renal denervation and nephrectomy that can target pain produced by renal or hepatic cysts. Conclusions Chronic pain in patients with autosomal dominant polycystic kidney disease is often refractory to conservative, medical and other noninvasive treatments. There are effective surgical procedures that can be performed when more conservative treatments fail. Laparoscopic cyst decortication has been well studied and results in the relief of chronic renal pain in the majority of patients. In addition, renal denervation has been used successfully and could be performed concurrently with cyst decortication. Nephrectomy should be reserved for patients with intractable pain and renal failure when other modalities have failed.Item Native Nephrectomy with Renal Transplantation Decreases Hypertension Medication Requirements in Autosomal Dominant Polycystic Kidney Disease(Elsevier, 2016-01) Shumate, Ashley M.; Bahler, Clinton D.; Goggins, William C.; Sharfuddin, Asif A.; Sundaram, Chandru P.; Department of Urology, IU School of MedicinePurpose We assessed hypertensive control after native nephrectomy and renal transplantation in patients with autosomal dominant polycystic kidney disease. Materials and Methods Blood pressure control was studied retrospectively in 118 patients with autosomal dominant polycystic kidney disease who underwent renal transplantation between 2003 and 2013. Overall 54 patients underwent transplantation alone (group 1) and 64 underwent transplantation with concurrent ipsilateral nephrectomy (group 2). Of these 64 patients 32 underwent ipsilateral nephrectomy only (group 2a) and 32 underwent eventual delayed contralateral native nephrectomy (group 2b). The number of antihypertensive drugs and defined daily dose of each antihypertensive was recorded at transplantation and up to 36-month followup. Results Comparing preoperative to postoperative medications at 12, 24 and 36-month followup, transplantation with concurrent ipsilateral nephrectomy had a greater decrease in quantity (−1.2 vs −0.5 medications, p=0.008; −1.1 vs −0.3, p=0.007 and −1.2 vs −0.4, p=0.03, respectively) and defined daily dose of antihypertensive drug (−3.3 vs −1.0, p=0.0008; −2.9 vs −1.0, p=0.006 and −2.7 vs −0.6, p=0.007, respectively) than transplantation alone at each point. Native nephrectomy continued to be a predictor of hypertensive requirements on multivariable analysis (p <0.0001). The mean decrease in number of medications in group 2b from after ipsilateral nephrectomy to 12 months after contralateral nephrectomy was −0.6 (p=0.0005) and the mean decrease in defined daily dose was −0.6 (p=0.009). Conclusions In patients with autosomal dominant polycystic kidney disease undergoing renal transplantation, concurrent ipsilateral native nephrectomy is associated with a significant decrease in the quantity and defined daily dose of antihypertensive drugs needed for hypertension control. Delayed contralateral native nephrectomy is associated with improved control of blood pressure to an even greater degree.Item A novel preoperative model to predict 90-day surgical mortality in patients considered for renal cell carcinoma surgery(Elsevier, 2018-10) Calaway, Adam C.; Monn, M. Francesca; Bahler, Clinton D.; Cary, Clint; Boris, Ronald S.; Urology, School of MedicineIntroduction Surgical benefits for renal cell carcinoma must be weighed against competing causes of mortality, especially in the elderly patient population. We used a large cancer registry to evaluate the impact of patient and cancer-specific factors on 90-day mortality (90DM). A nomogram to predict the odds of short-term mortality was created. Materials and Methods The National Cancer Database was queried to identify all patients with clinically localized, nonmetastatic disease treated with partial or radical nephrectomy. Using a random sample of 60%, multiple logistic regression with 90DM outcomes were performed to identify preoperative variables associated with mortality. Variables included age, sex, race, co-morbidity score, tumor size, and presence of a thrombus. A nomogram was created and tested on the remaining 40% of patients to predict 90DM. Results 183,407 patients met inclusion criteria. Overall 90DM for the cohort was 1.9%. All preoperative variables significantly influenced the risk of 90DM. Patient age was by far the strongest predictor. Nomogram scores ranged from 0 to 12. Compared to patients with 0 to 1 points, those with 2 to 3 (odds ratio [OR] 2.89, 2.42–3.46; P < 0.001), 4 to 5 (OR 6.25, 5.26–7.43; P < 0.001), and >6 (OR 12.86, 10.83–15.27; P < 0.001) were at incrementally significantly higher odds of 90DM. Being >80 years of age alone placed patients into the highest risk of surgical mortality. Conclusions Management of localized kidney cancer must consider competing causes of mortality, especially in elderly patients with multiple co-morbidities. We present a preoperative tool to calculate risk of surgical short-term mortality to aid surgeon–patient counseling.Item Novel Use of Folate-Targeted Intraoperative Fluorescence, OTL38, in Robot-Assisted Laparoscopic Partial Nephrectomy: Report of the First Three Cases(Mary Ann Liebert, 2016) Shum, Cheuk Fan; Bahler, Clinton D.; Low, Philip S.; Ratliff, Timothy L.; Kheyfets, Steven V.; Natarajan, Jay P.; Sandusky, George E.; Sundaram, Chandru P.; Department of Urology, IU School of MedicinePartial nephrectomy is now the preferred surgical option for small renal tumors because it allows nephron preservation without compromising oncologic clearance. Its outcomes depend on the surgeon's ability to continuously identify the edges of the tumor during resection, thus leaving an adequate margin around the tumor without excessive removal of normal parenchyma, as well as keeping a short ischemic time. Folate receptors are highly abundant in the normal kidney, and there is a difference in folate receptor expression between malignant and normal renal tissues. Thus, the use of fluorescent agents that target folate receptors should result in differential fluorescence between the tumor and surrounding parenchyma during partial nephrectomy, which, in turn, helps tumor demarcation for identification and resection. A phase 2 study on the novel use of OTL38 in robot-assisted laparoscopic partial nephrectomy is currently in progress in our institution. The outcomes of the first three cases have shown the possible advantages of OTL38 in intraoperative tumor identification before resection and recognition of residual disease in the surrounding parenchyma after resection. The tumors typically appeared dark while the surrounding parenchyma showed brighter fluorescence. Immediately after tumor resection, the margins of all the specimens appeared to have a uniformly bright fluorescence, suggestive of an intact margin of normal renal parenchyma along the plane of excision. The pattern of intraoperative fluorescence correlates well with immunohistochemistry. No OTL38-related adverse effects have been seen among these three patients. We present the outcomes of these three cases, illustrated with intraoperative and immunohistochemistry images.