Effect of alanine supplementation on oxalate synthesis.

The Primary Hyperoxalurias (PH) are rare disorders of metabolism leading to excessive endogenous synthesis of oxalate and recurring calcium oxalate kidney stones. Alanine glyoxylate aminotransferase (AGT), deficient in PH type 1, is a key enzyme in limiting glyoxylate oxidation to oxalate. The affinity of AGT for its co-substrate, alanine, is low suggesting that its metabolic activity could be sub-optimal in vivo. To test this hypothesis, we examined the effect of L-alanine supplementation on oxalate synthesis in cell culture and in mouse models of Primary Hyperoxaluria Type 1 (Agxt KO), Type 2 (Grhpr KO) and in wild-type mice. Our results demonstrated that increasing L-alanine in cells decreased synthesis of oxalate and increased viability of cells expressing GO and AGT when incubated with glycolate. In both wild type and Grhpr KO male and female mice, supplementation with 10% dietary L-alanine significantly decreased urinary oxalate excretion ~30% compared to baseline levels. This study demonstrates that increasing the availability of L-alanine can increase the metabolic efficiency of AGT and reduce oxalate synthesis.

Factors Associated With Postoperative Infection After Percutaneous Nephrolithotomy.

Numerous studies have investigated risk factors for the development of postoperative infection in percutaneous nephrolithotomy (PCNL) patients. Herein, we describe our meta-analysis of the risk factors for the prediction of post-PCNL infectious complications. We searched electronic databases using a combination of the terms percutaneous nephrolithotomy, risk factors, infection, and sepsis. The primary outcome was post-PCNL infection as defined by fever >38°C or sepsis as defined by the Sepsis Consensus Definition Committee. Risk factors for infection in each study were identified and included for analysis if present in at least two studies. We used quantitative effect sizes in odds ratio to assess each endpoint. After application of criteria, 24 studies were found, of which 12 were prospective and 12 were retrospective. Of the prospective studies, preoperative urine culture, renal pelvis culture, stone culture, number of access points, hydronephrosis, perioperative blood transfusion, and struvite stone composition were found to be significantly associated with postoperative infection. Of the 12 retrospective studies, preoperative urine culture, stone cultures, number of access points, blood transfusion, stone size, and staghorn formation were associated with infection. Preoperative urine culture, stone culture, number of access points, and need for blood transfusion were consistently found to be significant factors. This indicates that the presence of bacteria in the urine/stone preoperatively as well as the amount of trauma the kidney sustains during the procedure are major predictors of postoperative infection.

MRI/US fusion-guided prostate biopsy allows for equivalent cancer detection with significantly fewer needle cores in biopsy-naive men.

PURPOSE: We aimed to investigate the efficiency and cancer detection of magnetic resonance imaging (MRI) / ultrasonography (US) fusion-guided prostate biopsy in a cohort of biopsy-naive men compared with standard-of-care systematic extended sextant transrectal ultrasonography (TRUS)-guided biopsy. METHODS: From 2014 to 2016, 72 biopsy-naive men referred for initial prostate cancer evaluation who underwent MRI of the prostate were prospectively evaluated. Retrospective review was performed on 69 patients with lesions suspicious for malignancy who underwent MRI/US fusion-guided biopsy in addition to systematic extended sextant biopsy. Biometric, imaging, and pathology data from both the MRI-targeted biopsies and systematic biopsies were analyzed and compared. RESULTS: There were no significant differences in overall prostate cancer detection when comparing MRI-targeted biopsies to standard systematic biopsies (P = 0.39). Furthermore, there were no significant differences in the distribution of severity of cancers based on grade groups in cases with cancer detection (P = 0.68). However, significantly fewer needle cores were taken during the MRI/US fusion-guided biopsy compared with systematic biopsy (63% less cores sampled, P < 0.001) CONCLUSION: In biopsy-naive men, MRI/US fusion-guided prostate biopsy offers equal prostate cancer detection compared with systematic TRUS-guided biopsy with significantly fewer tissue cores using the targeted technique. This approach can potentially reduce morbidity in the future if used instead of systematic biopsy without sacrificing the ability to detect prostate cancer, particularly in cases with higher grade disease.

Incidental findings on multiparametric MRI performed for evaluation of prostate cancer.

PURPOSE: Multiparametric magnetic resonance imaging (mp-MRI) and MRI/Ultrasound (US) fusion-guided biopsy are relatively new techniques for improved detection, staging, and active surveillance of prostate cancer (PCa). As with all imaging modalities, MRI reveals incidental findings (IFs) which carry the risk of increased cost, patient anxiety, and iatrogenic morbidity due to workup of IFs. Herein, we report the IFs from 684 MRIs for evaluation of PCa and consider their characteristics and clinical significance. METHODS: Patients underwent mp-MRI prostate protocol incorporating triplanar T2-weighted, diffusion-weighted, and dynamic contrast-enhanced pelvic MRI as well as a post-contrast abdominopelvic MRI with the primary indication of detection or evaluation of PCa. A total of 684 consecutive prostate MRI reports performed in a series of 580 patients were reviewed. All extraprostatic findings reported were logged and then categorized by organ system and potential clinical significance. RESULTS: There were 349 true IFs found in 233 (40%) of the 580 patients. One hundred nineteen additional extraprostatic findings were unsuspected but directly related to PCa staging, while the 349 IFs were unrelated and thus truly incidental beyond study indication. While the majority of true IFs were non-urologic, only 6.6% of IFs were considered clinically significant, non-urologic findings, and more than a third of MRI reports had urologic IFs not related to PCa. CONCLUSIONS: Rates of incidental findings on prostate indication MRI are similar to other abdominopelvic imaging studies. However, only 6.6% of the IFs were considered to be clinically significant non-urologic findings. Further investigations are needed to assess downstream workup of these IFs and resulting costs.

Pathologic and clinical characteristics of early onset renal cell carcinoma.

The majority of renal cell carcinomas (RCCs) occur within the 7th decade of life, uncommonly arising in adults ≤46 years. We reviewed the clinicopathologic features of early onset RCC and evaluated the role of immunohistochemistry (IHC) in potentially identifying diagnoses of newly recognized RCC subtypes that may have been previously misclassified. A retrospective review was performed from 2011-2016 for cases of RCC. Early onset RCC was defined as ≤46 years of age. Clinicopathologic findings and hematoxylin and eosin (H&E) slides were reviewed on early onset RCC patients. IHC was performed on all cases previously diagnosed as unclassified or papillary. Clinicopathologic findings were compared to a control group of RCC patients >46 years over the same time period. We identified 98/598 (16.4%) early onset RCCs. The median age in the early onset RCC and control group was 38.4 and 62.8 years, respectively. The early onset RCC group contained 33/96 (34.3%) females and 63/96 (65.6%) males, including 52/96 (54.2%) whites, 39/96 (40.6%) African Americans, 4/96 (4.2%) Hispanics, and 1/96 (1%) Asian. Nonwhites were significantly more likely to develop early onset RCC (P=.004). Early onset RCCs included 52% clear cell, 28.6% papillary, 8.2% unclassified, 5.1% chromophobe, 3.1% clear cell papillary(CCP), and 3 other rare tumors. Six unclassified and 26 papillary RCCs had tissue available for IHC. Two of 6 (33.3%) unclassified RCCs were reclassified (1 CCP, 1 Xp11 translocation). One of 26 (3.8%) papillary RCCs was reclassified as CCP. Early onset RCCs were more likely to occur in nonwhites (P=.004), be lower stage (P=.03), and undergo partial nephrectomy (P=.002). Few unclassified and papillary tumors were reclassified with IHC.

Second Opinion Expert Pathology Review in Bladder Cancer: Implications for Patient Care.

OBJECTIVES: To review bladder specimens referred to our facility for secondary review to determine the frequency and degree of changes in pathological diagnoses, which could affect patient care. METHODS: A retrospective review of 246 bladder specimens sent to our pathology department for second opinion pathological review was performed. All consultation specimens were reviewed by a single genitourinary (GU)-subspecialized surgical pathologist. Any changes in the pathological grade, stage, or histological tumor type were noted as well as patient demographic data. Statistical analysis was performed to determine the frequency and type of discrepancies in diagnoses and determine any associations with patient demographic parameters. RESULTS: Secondary pathology consultation of 246 bladder specimens from 233 patients were reviewed and compared with the primary diagnosis. The diagnosis was altered in 91/246 cases (37.0%). The number of cases reviewed per patient and specimen type was not associated with a change in diagnosis ( P = .19; P = .1). Of the cases with a change in diagnosis, 8 (8.8%) changed malignancy status, 46 (50.5%) changed stage, 16 (17.6%) changed tumor type (ie, change from urothelial carcinoma to prostate adenocarcinoma), 16 (17.6%) changed histological variant subtype, and 14 (15.4%) changed grade. There was no association noted between age, gender, or race and changes in diagnosis ( P = .53; P = .41; P = .70). CONCLUSIONS: Secondary pathology review with a GU-subspecialized surgical pathologist can change the stage, grade, or histological subtype on bladder biopsy and tumor resection specimens in more than one-third of cases. Age and gender were not associated with the frequency of change in diagnosis on consultation review.

Co-registration of MRI and ultrasound: accuracy of targeting based on radiology-pathology correlation.

We reviewed the role of multiparametric magnetic resonance imaging (MP-MRI) and methods of MRI guided biopsy including in-bore, cognitive fusion, and software-based fusion. MP-MRI has been developed, optimized, and studied as a means of improving prostate cancer detection beyond the standard evaluation that utilizes digital rectal examinations and serum prostate specific antigen (PSA). MP-MRI has been proven to be an excellent diagnostic imaging modality that improves prostate cancer detection and risk stratification by guiding biopsy samples. The co-registration between MRI and ultrasound has allowed for software-based fusion which enables office-based biopsy procedures while still benefiting from the detailed prostate characterization of MRI. MP-MRI/ultrasound fusion guided biopsy has been studied in detail as this technology has been developed, tested, and validated in the past decade. The imaging to pathology correlation supporting the use of MP-MRI/ultrasound fusion is well documented in the literature. As the indication for the use of prostate MP-MRI becomes more widespread, it is important to continue to evaluate the correlation between imaging and pathologic findings.

Factors predicting prostate cancer upgrading on magnetic resonance imaging-targeted biopsy in an active surveillance population.

BACKGROUND: The objective of this study was to create a nomogram model integrating clinical and multiparametric magnetic resonance imaging (MP-MRI)-based variables to predict prostate cancer upgrading in a population of active surveillance (AS) patients. METHODS: Prostate cancer patients on AS who underwent MP-MRI with magnetic resonance imaging (MRI)/ultrasound (US) fusion-guided biopsy were identified. Clinical and imaging variables, including the prostate-specific antigen density (PSAD), number of lesions, total lesion volume, total lesion density, Prostate Imaging Reporting and Data System magnetic resonance imaging suspicion score (MRI-SS), and duration between prereferral systematic and MRI/US fusion-guided biopsy sessions, were assessed. Logistic regression modeling was used to assess upgrading on MRI/US fusion-guided biopsy. A predictive model for upgrading was calculated with the significant factors identified. RESULTS: Seventy-six patients were analyzed with a mean age of 62.5 years and a median prostate-specific antigen (PSA) level of 5.1 ng/mL. The average duration between prereferral and MRI/US biopsies was 21 months. Twenty patients (26.32%) were upgraded. The PSAD, duration between prereferral and MRI/US biopsies, MRI-SS, and MRI total lesion density were significantly associated with upgrading. A logistic regression model using these factors to predict upgrading on confirmatory MRI/US fusion biopsy had an area under the curve (AUC) of 0.84, whereas the AUC was 0.69 with PSA alone. On the basis of this model, a nomogram was generated, and using a probability cutoff of 22% as an indication of upgrading, it produced sensitivity, specificity, positive predictive, and negative predictive values of 80%, 81.25%, 57.1%, and 92.86%, respectively. CONCLUSIONS: The integration of MRI findings with clinical parameters can add value to a model predicting upgrading from a Gleason score of 3 + 3 = 6 in men on AS. This can potentially be used as a noninvasive approach to confirm AS patients with low-risk disease for whom biopsy may be deferred. Cancer 2017;123:1941-1948. © 2017 American Cancer Society.

Safety and Efficacy of En Bloc Renal Hilar Vascular Staple Ligation: A Meta-Analysis.

PURPOSE: We reviewed the literature on the safety of en bloc ligation. We also performed a meta-analysis of the effect of using this technique with vascular staplers on perioperative factors compared to conventional renal pedicle dissection and isolated staple ligation of the renal artery and vein. MATERIALS AND METHODS: A literature search was performed to include all primary studies related to the safety of en bloc ligation of the renal hilum. After exclusion criteria were applied 9 studies were identified for review, of which 4 included a control group and were used in the meta-analysis. The primary end point was the incidence of arteriovenous fistula. Secondary end points were procedure duration, blood loss and the number of perioperative complications. RESULTS: None of the total population of 595 patients in whom en bloc ligation was performed for nephrectomy were diagnosed with arteriovenous fistula formation at an average postoperative followup of 26.5 months. When comparing en bloc and isolated ligation of the renal artery and vein, the meta-analysis showed a significant improvement in procedure duration for en bloc nephrectomy. There was no difference in estimated blood loss or the number of complications. CONCLUSION: En bloc ligation appears to be as safe as and potentially more beneficial in terms of perioperative factors than conventional renal pedicle dissection and isolated vascular ligation.

Complete Tissue Submission to Increase Lymph Node Detection in Pelvic Lymph Node Packets Submitted for Patients Undergoing Radical Prostatectomy and Radical Cystectomy.

BACKGROUND: Pelvic lymphadenectomy has prognostic and therapeutic implications in both bladder and prostate cancer. Pelvic lymphadenectomy specimens are fatty and identification of lymph nodes (LNs) can be difficult during the grossing process. We investigated the benefit of a new grossing method requiring entire LN packet submission. MATERIALS/METHODS: We introduced a new grossing protocol requiring total submission of LN packets for patients undergoing radical prostatectomy (RP) or radical cystectomy (RC). A retrospective review was performed to evaluate clinical and pathologic data for RP (n = 59) and RC (n = 56) cases performed 18 months prior to and 18 months following implementation of the new lymphadenectomy grossing protocol. RESULTS: For RP and RC cases, significantly more LNs were found when total LN packets were submitted with the new technique: mean 14.1 versus 8.7, and mean 25.2 versus 15.9, respectively ( P = .007, P = .011). For RP cases, there was no significant change in the number of LN packets submitted for evaluation from the operating room ( P = .76). For RC cases, more LNs were found with the new technique despite a significantly fewer number of LN packets sent from the operating room in the cohort that were processed with the new technique: mean 2.2 versus 4.0 LN packets ( P < .001). Significantly more paraffin blocks were required using the new grossing method for both RP and RC: mean 13.53 versus 6.9 and mean 19.0 versus 12.4, respectively ( P < .001, P = .018). CONCLUSIONS: Submitting all additional fatty tissue after palpable identification of LNs can significantly increase the detection of LNs in RP and RC cases.

Assessing the Costs of Extraurinary Findings of Computed Tomography Urogram in the Evaluation of Asymptomatic Microscopic Hematuria.

OBJECTIVE: To assess the costs associated with incidental extraurinary findings on computed tomography urogram (CTU) in patients with asymptomatic microscopic hematuria. MATERIALS AND METHODS: A retrospective review was performed to identify all CTUs performed for asymptomatic microscopic hematuria at our institution from 2012 to 2014. All genitourinary (GU) and incidental extraurinary findings were documented. Further clinical follow-up to May 2015 was reviewed to determine if any referrals, tests, imaging, and/or procedures were ordered based on the initial CTU. Cost estimates were determined using the Medicare physician reimbursement rate. RESULTS: Two hundred two patients were evaluated with CTU for asymptomatic microscopic hematuria. GU malignancy was documented in 2 patients (0.99%), both renal masses suspicious for renal cell carcinoma. Sixty patients were found to have kidney stones, of which 26 had stones ≥5 mm. Incidental extraurinary findings were found in 150 (74.3%) patients, requiring further imaging costs of $17,242 or $85.35 per patient screened. Twelve patients required a total of 20 procedures for a cost of $54,655. The total cost related to extraurinary findings was $140,290 or $694.50 per initial patient screened. CONCLUSION: The incidental extraurinary findings detected on CTU can lead to expensive and invasive testing and treatment. Whereas costs associated with further workup were high, the overall outcomes in both GU and non-GU cancer diagnosis were low. Future analysis should focus on limiting the cost and invasiveness of our evaluation for this condition.

The Role of Antibiotic Prophylaxis in Percutaneous Nephrolithotomy.

Postoperative sepsis is the most common cause of mortality after percutaneous nephrolithotomy (PCNL) procedures. Studies investigating the use of antibiotics in PCNL patients have shown that prophylactic antibiotic regimens can reduce the rate of postoperative infectious complications. In addition, several studies have identified risk factors for sepsis development that can help guide antibiotic treatment and perioperative care overall. This has led the American Urological Association to recommend antibiotic prophylaxis for PCNL as a best practice policy statement. However, despite prophylaxis, postoperative sepsis has continued to remain the leading cause of mortality in PCNL patients. In addition, multiple antibiotic protocols exist within the guideline realms. This review assesses the development and role of antibiotic prophylaxis for PCNL procedures.

Testosterone replacement therapy in patients with prostate cancer after radical prostatectomy.

PURPOSE: Testosterone replacement therapy in men with prostate cancer is controversial, with concern that testosterone can stimulate cancer growth. We evaluated the safety and efficacy of testosterone in hypogonadal men with prostate cancer treated with radical prostatectomy. MATERIALS AND METHODS: We performed a review of 103 hypogonadal men with prostate cancer treated with testosterone after prostatectomy (treatment group) and 49 nonhypogonadal men with cancer treated with prostatectomy (reference group). There were 77 men with low/intermediate (nonhigh) risk cancer and 26 with high risk cancer included in the analysis. All men were treated with transdermal testosterone, and serum hormone, hemoglobin, hematocrit and prostate specific antigen were evaluated for more than 36 months. RESULTS: Median (IQR) patient age in the treatment group was 61.0 years (55.0-67.0), and initial laboratory results included testosterone 261.0 ng/dl (213.0-302.0), prostate specific antigen 0.004 ng/ml (0.002-0.007), hemoglobin 14.7 gm/dl (13.3-15.5) and hematocrit 45.2% (40.4-46.1). Median followup was 27.5 months, at which time a significant increase in testosterone was observed in the treatment group. A significant increase in prostate specific antigen was observed in the high risk and nonhigh risk treatment groups with no increase in the reference group. Overall 4 and 8 cases of cancer recurrence were observed in treatment and reference groups, respectively. CONCLUSIONS: Thus, testosterone therapy is effective and, while followed by an increase in prostate specific antigen, does not appear to increase cancer recurrence rates, even in men with high risk prostate cancer. However, given the retrospective nature of this and prior studies, testosterone therapy in men with history of prostate cancer should be performed with a vigorous surveillance protocol.