Cory M. Hugen

Size Does Matter: Donor Renal Volume Predicts Recipient Function Following Live Donor Renal Transplantation

PURPOSE With the now routine use of computerized tomography angiography with 3-dimensional reconstruction in the donor evaluation, renal volume can be easily determined using volume calculating software. We evaluated whether donor renal volume could predict recipient renal function. MATERIALS AND METHODS Clinical data of all donor and recipient pairs undergoing live donor kidney transplantation at our institution between January 2006 and October 2009 were reviewed. The volume of the kidney selected for transplant was determined using volume calculating software, and correlated to transplant recipient nadir and 1-year serum creatinine. Multivariate regression analysis was performed to adjust for demographic and clinical variables. RESULTS During the study period 114 patients underwent live donor renal transplantation. Recipient nadir and 1-year serum creatinine levels were significantly correlated with the volume of donated kidney even after adjusting for age, body mass index, body surface area and donor creatinine clearance. Kidney volume also retained significance after excluding recipients from analysis who experienced acute rejection episodes. CONCLUSIONS Larger kidney volumes calculated using 3-dimensional computerized tomography with volume calculating software are correlated with lower recipient nadir and 1-year serum creatinine levels.

Prognostic variables and nomograms for renal cell carcinoma

The term renal cell carcinoma (RCC) is used to describe a heterogeneous group of tumors that vary histologically, genetically and molecularly. Extensive research has been conducted to identify characteristics that predict outcomes among patients with RCC. In addition to histological subtype these include tumor size, patient age, mode of presentation and various hematological indices, among others. Several groups have incorporated these clinical and pathological features into nomograms which help the clinician better define individual patient prognosis and direct the optimum therapeutic approach. In the present article we review these prognostic variables and nomograms for RCC.

Comparison of Open and Robot-Assisted Pelvic Lymphadenectomy for Prostate Cancer

PURPOSE We evaluated whether there were differences in the lymph node yield and incidence of nodal metastasis among patients undergoing robot-assisted radical prostatectomy with pelvic lymphadenectomy (LAD) and open radical retropubic prostatectomy with either a standard or extended node dissection. PATIENTS AND METHODS Data were collected retrospectively on all patients undergoing radical prostatectomy with pelvic LAD at our institution between January 2006 and December 2008. Patients in group 1 (n = 60) underwent robot-assisted standard LAD, those in group 2 (n = 64) had open standard LAD, and group 3 patients (n = 43) were treated with open extended LAD. Statistical comparison was then made between the three groups stratified by histologic grade and pathologic stage. RESULTS The mean lymph node yield was 8.2 for group 1, 7.6 for group 2, and 14.8 for group 3. The overall incidence of positive nodes in each group was 3.3%, 1.6%, and 18.6%, respectively. There were no differences between the node counts (P = 0.84) and probability of finding positive nodes between the robot-assisted and open standard dissections. The extended LAD identified patients with positive nodes at a greater frequency, although those patients were more likely to have adverse pathologic features. Complications related to the lymphadenectomy were not different between the groups. CONCLUSION The lymph node yield obtained during robot-assisted pelvic lymphadenectomy for prostate cancer is comparable to an open approach using a similar template. An open extended node dissection yields more nodes and identifies a greater number of patients with lymph node involvement.

Sequential Intravesical Mitomycin plus Bacillus Calmette–Guérin for Non–Muscle-Invasive Urothelial Bladder Carcinoma: Translational and Phase I Clinical Trial

Purpose: To determine the safety and toxicities of sequential MMC (mitomycin C) + BCG (bacillus Calmette–Guérin) in patients with non–muscle-invasive bladder cancer (NMIBC) and explore evidence for potentiation of BCG activity by MMC. Experimental Design: A 3 + 3 phase I dose-escalation trial of six weekly treatments was conducted in patients with NMIBC. MMC (10, 20, or 40 mg) was instilled intravesically for 30 minutes, followed by a 10-minute washout with gentle saline irrigation and then instillation of BCG (half or full strength) for 2 hours. Urine cytokines were monitored and compared with levels in a control cohort receiving BCG only. Murine experiments were carried out as described previously. Results: Twelve patients completed therapy, including 3 patients receiving full doses. The regimen was well tolerated with no treatment-related dose-limiting toxicities. Urinary frequency and urgency, and fatigue were common. Eleven (91.7%) patients were free of disease at a mean (range) follow-up of 21.4 (8.4–27.0) months. Median posttreatment urine concentrations of IL2, IL8, IL10, and TNFα increased over the 6-week treatment period. A greater increase in posttreatment urinary IL8 during the 6-week period was observed in patients receiving MMC + BCG compared with patients receiving BCG monotherapy. In mice, intravesical MMC + BCG skewed tumor-associated macrophages (TAM) toward a beneficial M1 phenotype. Conclusions: Instillation of sequential MMC + BCG is safe tolerable up to 40-mg MMC plus full-strength BCG. This approach could provide improved antitumor activity over BCG monotherapy by augmenting beneficial M1 TAMs. Clin Cancer Res; 21(2); 303–11. ©2014 AACR.

Illinois Statewide Dual Kidney Transplantation Experience—Are We Appropriately Selecting Kidneys?

PURPOSE Dual kidney transplantation is a technique that some transplant centers have adopted to increase organ use. We investigated whether kidneys that were recovered and discarded were similar to those kidneys used for dual kidney transplantation. MATERIALS AND METHODS We reviewed all kidneys recovered, biopsied and placed on machine perfusion in the state of Illinois from January 2002 to October 2009. We selected those kidneys used in dual kidney transplant, and compared their characteristics to those of kidneys that were recovered and biopsied but ultimately discarded. The immediate and 1-year outcomes of the dual kidney transplant recipients were analyzed. RESULTS During the study period 60 dual transplants were performed while 94 kidney pairs were discarded. Overall donors from the used group had a lower mean creatinine clearance, older mean patient age, lower percentage of glomerulosclerosis, higher final flow rate and lower resistance. However, the comparison between those kidneys used successfully with 1-year graft survival and those discarded demonstrated only 3 less favorable parameters among the discarded group, namely a higher percentage of glomerulosclerosis (18.5% vs 13.9%, p=0.024), a higher degree of interstitial fibrosis and a higher final resistance (0.39 vs 0.31, p<0.001). CONCLUSIONS The considerable overlap in demographics, histology and perfusion parameters between used and discarded kidneys suggests that many kidneys that were recovered and discarded could have been used in dual kidney transplantation with acceptable outcomes. This highlights the need for further study of how kidneys are selected and used.

Risk factors for recurrence following radical cystectomy for pathologic node negative bladder cancer

To evaluate for risk factors associated with bladder cancer recurrence in patients with pathologically negative lymph nodes.

Transplant tourism - a dangerous journey?

Polcari AJ, Hugen CM, Farooq AV, Holt DR, Hou SH, Milner JE. Transplant tourism – a dangerous journey?
Clin Transplant 2011: 25: 633–637.

Lymph node dissection in bladder cancer: Where do we stand?

Abstract Radical cystectomy with lymphadenectomy remains the standard-of-care treatment for muscle-invasive bladder cancer. Lymphadenectomy is a central component of the operation because it continues to play both diagnostic and therapeutic roles. Routinely available preoperative imaging has limited diagnostic accuracy as it relies mostly on size to identify nodal metastasis increasing the value of lymphadenectomy. While the merits of lymphadenectomy are not in question, the extent of lymphadenectomy required to provide maximum benefit while limiting morbidity remains controversial. Furthermore, although robotic-assisted surgery has gained popularity in many centers, concern remains regarding the learning curve required and skill needed to replicate the quality of an open lymphadenectomy. Research efforts have been focused on these unresolved issues, and several trials are currently ongoing to help address these knowledge deficit areas. In this update, we will focus on the current state of lymphadenectomy for bladder cancer and highlight recent advances.

Utilization of retroperitoneal lymph node dissection for testicular cancer in the United States: Results from the National Cancer Database (1998-2011).

INTRODUCTION Retroperitoneal lymph node dissection (RPLND) for the treatment of testicular cancer is a relatively rare and complex operation that may contribute to differences in utilization. We sought to characterize the use of RPLND between different categories of cancer center facilities in the United States. MATERIALS AND METHODS The National Cancer Database was queried for patients with germ cell tumors treated at different types of cancer centers between 1998 and 2011. The proportion of patients who underwent RPLND was stratified by stage and histology and then compared between treatment facilities. RPLND utilization was then compared between facility types as a function of time. RESULTS A total of 59,652 patients met inclusion criteria and 5,475 (9.2%) underwent RPLND. The proportion of patients treated with RPLND for non-seminomatous germ cell tumor (NSGCT) was significantly different between cancer center types for all stages (P<0.001) and used most often in academic comprehensive cancer centers. There was no difference in the proportion of RPLND utilization for stage II and III seminoma stratified by treatment facility. There was a significantly decreased trend in the utilization of RPLND for stage I (P = 0.032) NSGCT whereas utilization was increased for stage III NSGCT (P≤0.001) over the study period. CONCLUSIONS The proportion of patients undergoing RPLND for NSGCT varies significantly by the type of cancer center and is used most often in academic cancer centers. Utilization of RPLND decreased for stage I NSGCT and increased for stage III NSGCTs during the study period.

Circulating Tumor Cells in Genitourinary Malignancies: An Evolving Path to Precision Medicine

Precision medicine with molecularly directed therapeutics is rapidly expanding in all subspecialties of oncology. Molecular analysis and treatment monitoring require tumor tissue, but resections or biopsies are not always feasible due to tumor location, patient safety, and cost. Circulating tumor cells (CTCs) offer a safe, low-cost, and repeatable tissue source as an alternative to invasive biopsies. “Liquid biopsies” can be collected from a peripheral blood draw and analyzed to isolate, enumerate, and molecularly characterize CTCs. While there is deserved excitement surrounding new CTC technologies, studies are ongoing to determine whether these cells can provide reliable and accurate information about molecular drivers of cancer progression and inform treatment decisions. This review focuses on the current status of CTCs in genitourinary (GU) cancer. We will review currently used methodologies to isolate and detect CTCs, their use as predictive biomarkers, and highlight emerging research and applications of CTC analysis in GU malignancies.