Faculty Bibliography

INTRODUCTION/BACKGROUND:Local prostate cancer recurrence following radiotherapy (XRT) or cryoablation (CRYO) may be addressed with salvage cryotherapy (SCT), although little is known about how the primary treatment modality affects SCT results. Oncologic and functional outcomes of patients who underwent SCT after primary XRT (XRT-SCT) or cryoablation (CRYO-SCT) were studied. METHODS:Data was collected using the Duke Prostate Cancer database and the Cryo On-Line Data (COLD) registry. The primary outcome was biochemical progression-free survival (BPFS).  Urinary incontinence, rectourethral fistula, and erectile dysfunction were secondary outcomes. The Kaplan-Meier log-rank test and univariable/multivariable Cox proportional hazards (CPH) models were utilized to evaluate BPFS between groups. RESULTS:419 XRT-SCT and 63 CRYO-SCT patients met inclusion criteria, that was reduced to 63 patients in each cohort after propensity matching. There was no difference in BPFS at 2 and 5 years both before (P = .5 and P = .7) and after matching (P = .6 and P = .3). On multivariable CPH, BPFS was comparable between treatment groups (CRYO-SCT, HR=1.1, [0.2-2.2]).  On the same analysis, BPFS was lower in D'Amico high-risk (HR 3.2, P < .01) and intermediate-risk (HR 1.95, P < .05) categories compared to low-risk. There was no significant difference in functional outcomes between cohorts. CONCLUSION/CONCLUSIONS:Following primary cryotherapy, salvage cryoablation provides comparable intermediate oncological outcomes and functional outcomes compared to primary radiotherapy.

BACKGROUND:There is no consensus on the optimal approach for salvage local therapy in radiation-resistant/recurrent prostate cancer (RRPC). OBJECTIVE:To investigate oncological and functional outcomes for men treated with salvage whole-gland cryoablation (SWGC) of the prostate for RRPC. DESIGN, SETTING, AND PARTICIPANTS/METHODS:We retrospectively reviewed our prospectively collected cryosurgery database between January 2002 and September 2019 for men who were treated with SWGC of the prostate at a tertiary referral center. INTERVENTION/METHODS:SWGC of the prostate. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS/METHODS:The primary outcome was biochemical recurrence-free survival (BRFS) according to the Phoenix criterion. Secondary outcomes included metastasis-free survival, cancer-specific survival, and adverse events. RESULTS AND LIMITATIONS/CONCLUSIONS:A total of 110 men with biopsy-proven RRPC were included in the study. Median follow-up for patients without biochemical recurrence (BCR) after SWGC was 71 mo (interquartile range [IQR] 42.3-116). BRFS was 81% at 2 yr and 71% at 5 yr. A higher prostate-specific antigen (PSA) nadir after SWGC was associated with worse BRFS. The median International Index of Erectile Function-5 score was 5 (IQR 1-15.5) before SWGC and 1 (IQR 1-4) after SWGC. Stress urinary incontinence, strictly defined as the use of any pads after treatment, was 5% at 3 mo and 9% at 12 mo. Clavien-Dindo grade ≥3 adverse events occurred in three patients (2.7%). CONCLUSIONS:In patients with localized RPPC, SWGC achieved excellent oncological outcomes with a low rate of urinary incontinence, and represents an alternative to salvage radical prostatectomy. Patients with fewer positive cores and lower PSA tended to have better oncological outcomes following SWGC. PATIENT SUMMARY/RESULTS:For men with prostate cancer that persists after radiotherapy, a freezing treatment applied to the whole prostate gland can achieve excellent cancer control. Patients who did not have elevated prostate-specific antigen (PSA) at 6 years after this treatment appeared to be cured.

BACKGROUND:This study reports the oncological and functional outcomes in men with localized prostate cancer (Pca) who were treated with primary whole gland cryoablation (WGC) of the prostate. METHODS:The authors retrospectively reviewed their prospectively collected cryosurgery database between January 2002 and September 2019 for men who were treated with WGC of the prostate at a tertiary referral center. Primary outcome includes biochemical recurrence-free survival (BRFS). Secondary outcomes include failure-free survival (FFS), metastasis-free survival (MFS) and adverse events. RESULTS:A total of 260 men were included in the study. Men having had prior treatment for Pca were excluded. Median follow-up was 107 months (interquartile range [IQR], 68.3-132.5 months). BRFS, FFS, and MFS at 10 years were 84%, 66%, and 96%, respectively. High risk D'Amico classification was associated with a lower BRFS and FFS on multivariable analysis. No patient had any Pca-related death during follow-up. American Urological Association symptoms score and bother index were unchanged following cryoablation. Median International Index of Erectile Function score precryoablation and post-cryoablation was 7 (IQR, 3-11) and 1 (IQR, 1-5), respectively. Stress urinary incontinence, defined as requiring any protective pads only occurred in five patients (2%). No patient developed a fistula. Grade > 2 Clavien-Dindo adverse events occurred in six (2.3%) patients. CONCLUSION/CONCLUSIONS:WGC of the prostate can achieve excellent oncological and functional outcomes in men with localized Pca at the 10-year mark. Primary WGC may be a good option for men who desire to preserve urinary continence and have an excellent oncologic outcome. LAY SUMMARY/BACKGROUND:Primary whole gland cryoablation is an alternative treatment option to radical prostatectomy and radiotherapy for men with organ-confined prostate cancer. Patients had excellent cancer outcomes 1 years after whole gland cryoablation, and patients with PSA nadir 0.1 ng/ml or lower after treatment were less likely to have disease recurrence.

Importance/UNASSIGNED:The diversity of pediatric genitourinary malignancies requires a timely resource detailing tumor characteristics and survival. Objective/UNASSIGNED:To determine the incidence, demographics, and outcomes of all pediatric genitourinary tumors within the United States. Methods/UNASSIGNED:A population-based search for patients diagnosed with genitourinary cancers under age 15 was performed using the National Cancer Institute's Surveillance, Epidemiology, and End Results 18 registry. Information on primary tumor location, histologic type, patient age, sex, year of diagnosis, race, treatment, cause of death, and survival months was extracted. Descriptive epidemiological and survival statistics were calculated for all variables. Results/UNASSIGNED:A total of 4576 cases from 1973 through 2015 were identified. The most common primary tumor sites were the kidney (80.3%), testis (12.3%), bladder (2.8%), and vagina (1.5%). Nephroblastoma (87.9%) and sarcoma (3.4%) were the most common renal malignancies. Rhabdomyosarcoma was common in the vagina, bladder, and testis at rates of 66.2%, 61.2%, and 24.6%, respectively. Germ cell tumors (71.0%) were the most common primary tumor of the testis. Ten-year overall survival (OS) for renal nephroblastoma and sarcoma was 88% and 82%, respectively. Ten-year OS for RMS of the testis was 91%, the bladder was 79%, the vagina was 79%, and the prostate was 56%. Germ cell tumor 10-year OS were 96% in the testis and 100% in the vagina. Interpretation/UNASSIGNED:A better understanding of the overall distribution and outcomes associated with pediatric genitourinary cancers allows physicians to best understand the patient's disease in the context of current frequency in a genitourinary setting and reported outcomes.

Misfolding and aggregation of disease-specific proteins, resulting in the formation of filamentous cellular inclusions, is a hallmark of neurodegenerative disease with characteristic filament structures, or conformers, defining each proteinopathy. Here we show that a previously unsolved amyloid fibril composed of a 135 amino acid C-terminal fragment of TMEM106B is a common finding in distinct human neurodegenerative diseases, including cases characterized by abnormal aggregation of TDP-43, tau, or α-synuclein protein. A combination of cryoelectron microscopy and mass spectrometry was used to solve the structures of TMEM106B fibrils at a resolution of 2.7 Å from postmortem human brain tissue afflicted with frontotemporal lobar degeneration with TDP-43 pathology (FTLD-TDP, n = 8), progressive supranuclear palsy (PSP, n = 2), or dementia with Lewy bodies (DLB, n = 1). The commonality of abundant amyloid fibrils composed of TMEM106B, a lysosomal/endosomal protein, to a broad range of debilitating human disorders indicates a shared fibrillization pathway that may initiate or accelerate neurodegeneration.

BACKGROUND:There is limited understanding about why sarcopenia is happening in bladder cancer, and which modifiable and nonmodifiable patient-level factors affect its occurrence. OBJECTIVE:The objective is to determine the extent to which nonmodifiable risk factors, modifiable lifestyle risk factors, or cancer-related factors are determining body composition changes and sarcopenia in bladder cancer survivors. DESIGN, SETTING, AND PARTICIPANTS:Patients above 18 yr of age with a histologically confirmed diagnosis of bladder cancer and a history of receiving care at Duke University Medical Center between January 1, 1996 and June 30, 2017 were included in this study. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:Bladder cancer survivors from our institution were assessed for their dietary intake patterns utilizing the Diet History Questionnaire II (DHQ-II) and physical activity utilizing the International Physical Activity Questionnaire long form (IPAQ-L) tools. Healthy Eating Index 2010 (HEI2010) scores were calculated from DHQ-II results. Body composition was evaluated using Slice-O-Matic computed tomography scan image analysis at L3 level and the skeletal muscle index (SMI) calculated by three independent raters. RESULTS AND LIMITATIONS:A total of 285 patients were evaluated in the study, and the intraclass correlation for smooth muscle area was 0.97 (95% confidence interval: 0.94-0.98) between raters. The proportions of patients who met the definition of sarcopenia were 72% for men and 55% of women. Univariate linear regression analysis demonstrated that older age, male gender, and black race were highly significant predictors of SMI, whereas tumor stage and grade, chemotherapy, and surgical procedures were not predictors of SMI. Multivariate linear regression analysis demonstrated that modifiable lifestyle factors, including total physical activity (p=0.830), strenuousness (high, moderate, and low) of physical activity (p=0.874), individual nutritional components (daily calories, p=0.739; fat, p=0.259; carbohydrates, p=0.983; and protein, p=0.341), and HEI2010 diet quality (p=0.822) were not associated with SMI. CONCLUSIONS:Lifestyle factors including diet quality and physical activity are not associated with SMI and therefore appear to have limited impact on sarcopenia. Sarcopenia may largely be affected by nonmodifiable risk factors. PATIENT SUMMARY:In this report, we aim to determine whether lifestyle factors such as diet and physical activity were the primary drivers of body composition changes and sarcopenia in bladder cancer survivors. We found that lifestyle factors including dietary habits, individual nutritional components, and physical activity do not demonstrate an association with skeletal muscle mass, and therefore may have limited impact on sarcopenia.

The left atrial appendage (LAA) is the most common site of thrombus formation in patients with atrial fibrillation. Therefore, better knowledge of the morphology, physiology, and function of the LAA may provide a better estimate of stroke risk. The LAA morphology is currently classified into 4 categories: chicken-wing (CW), windsock, cauliflower, and cactus. Chicken-wing is the most common and carries lower risk. This classification system, however, lacks consistent inter-rater reliability and correlation with stroke risk.