The prognostic value of digital rectal exam for the existence of advanced pathologic features after prostatectomy.

BACKGROUND: Accurate staging at the time of prostate cancer diagnosis is fundamental to risk stratification and management counseling. Digital rectal exam (DRE) is foundational in clinical staging of prostate cancer, even with a known limited interexaminer agreement and poor sensitivity for detecting extraprostatic disease. We sought to evaluate the prognostic value of DRE for the presence of advanced pathologic features (APFs) following radical prostatectomy (RP). METHODS: All patients undergoing RP as primary treatment for clinically localized prostate cancer in the National Cancer Database between 2008 and 2014 were identified. Patients with additional malignancies, prior treatment with radiation or systemic therapy, incongruent clinical staging and DRE findings or without fully evaluable clinical staging were excluded. The primary outcome was the presence of postsurgical APFs, defined as positive surgical margins, nodal disease, or pathologic stage T3 or greater. Multivariable logistic regression analysis was performed to account for prostate-specific antigen (PSA), biopsy grade group, percent of positive biopsy cores, and clinical stage. RESULTS: In total, 91,525 patients consisting of 69,182 cT1, 20,641 cT2, and 1702 cT3-T4 were included. The average age was 61.1 ± 7.0 years, and the average PSA was 8.6 ± 10.3 ng/ml. On multivariable analysis, cT3 and T4 were associated with the presence of APFs (odds ratio [OR] 11.12, p < .01 and 5.28, p = .04), however, cT2 was only slightly associated with the presence of APFs when compared with cT1 (OR 1.15, p < .01). Furthermore, cT2 was associated with more node-positive disease (OR 1.63, p < .01), positive margins (OR 1.06, p < .01), and more than or equal to pT3 disease (OR 1.22, p < .01). CONCLUSIONS: Overall, advanced clinical stage as assessed by DRE was independently associated with an increasing risk of APFs. For individual APFs, the greatest effect is noticed between clinical stage and nodal positivity and less so between clinical stage and positive margins. DRE continues to hold value, particularly for patients with locally advanced disease and potential lymph node disease.

A Novel Blood-Based Panel of Methylated DNA and Protein Markers for Detection of Early-Stage Hepatocellular Carcinoma.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) can be treated effectively if detected at an early stage. Recommended surveillance strategies for at-risk patients include ultrasound with or without α-fetoprotein (AFP), but their sensitivity is suboptimal. We sought to develop a novel, blood-based biomarker panel with improved sensitivity for early-stage HCC detection. METHODS: In a multicenter, case-control study, we collected blood specimens from patients with HCC and age-matched controls with underlying liver disease but without HCC. Ten previously reported methylated DNA markers (MDMs) associated with HCC, methylated B3GALT6 (reference DNA marker), and 3 candidate proteins, including AFP, were assayed and analyzed by a logistic regression algorithm to predict HCC cases. The accuracy of the multi-target HCC panel was compared with that of other blood-based biomarkers for HCC detection. RESULTS: The study included 135 HCC cases and 302 controls. We identified a multi-target HCC panel of 3 MDMs (HOXA1, EMX1, and TSPYL5), B3GALT6 and 2 protein markers (AFP and AFP-L3) with a higher sensitivity (71%, 95% CI: 60-81%) at 90% specificity for early-stage HCC than the GALAD score (41%, 95% CI: 30-53%) or AFP ≥7.32 ng/mL (45%, 95% CI: 33-57%). The AUC for the multi-target HCC panel for detecting any stage HCC was 0.92 compared with 0.87 for the GALAD score and 0.81 for AFP alone. The panel performed equally well in important subgroups based on liver disease etiology, presence of cirrhosis, or sex. CONCLUSIONS: We developed a novel, blood-based biomarker panel that demonstrates high sensitivity for early-stage HCC. These data support the potential for liquid biopsy detection of early-stage HCC to clinically benefit at-risk patients. This study was registered on ClinicalTrials.gov (NCT03628651).

Fistulous Complications following Radical Cystectomy for Bladder Cancer: Analysis of a Large Modern Cohort.

PURPOSE: Fistula formation is a rare and poorly described complication following radical cystectomy with urinary diversion. We sought to identify patients who experienced any type of fistulous complication and we analyzed risk factors for formation as well as management outcomes. MATERIALS AND METHODS: We retrospectively reviewed the records of patients who underwent radical cystectomy for bladder cancer at our institution. Patients who experienced any fistula were identified. Risk factors, management strategies and outcomes were analyzed. Patients underwent initial conservative treatment and those in whom this treatment failed underwent surgical repair. Univariable and multivariable analyses were performed to identify predictors of fistula formation as well as the need for surgical repair. RESULTS: Of the 1,041 patients 31 (3.0%) experienced fistula formation. Median time to fistula presentation was 31 days. Enterodiversion was the most common fistula type, noted in 54.8% of patients, followed by enterocutaneous and diversion cutaneous treatment in 29.0% and 12.9%, respectively. On multivariable analyses a history of radiation therapy (OR 3.1, p = 0.03) and an orthotopic neobladder (OR 3.1, p = 0.04) were predictors of fistula formation. Conservative management was successful in 41.9% of cases. There were no predictors of failed conservative management. Of patients who required surgical repair success was achieved in 94.4% at a single operation. CONCLUSIONS: Fistulas are rare after radical cystectomy and they are most common between the urinary diversion and the small bowel. A history of radiation therapy and a orthotopic neobladder are risk factors for formation. When required, surgical repair is generally successful at a single operation.

Non-muscle-invasive bladder cancer: Intravesical treatments beyond Bacille Calmette-Guérin.

An unmet need exists for patients with high-risk non-muscle-invasive bladder cancer for whom bacille Calmette-Guérin (BCG) has failed and who seek further bladder-sparing approaches. This shortcoming poses difficult management dilemmas. This review explores previously investigated first-line intravesical therapies and discusses emerging second-line treatments for the heterogeneous group of patients for whom BCG has failed. The myriad of recently published and ongoing trials assessing novel salvage intravesical treatments offer promise to patients who both seek an effective cure and want to avoid radical surgery. However, these trials must carefully be contextualized by specific patient, tumor, and recurrence characteristics. As data continue to accumulate, there will potentially be a role for these agents as second-line or even first-line intravesical therapies. Cancer 2017;123:390-400. © 2016 American Cancer Society.

Safety and early effectiveness of robot-assisted partial nephrectomy for large angiomyolipomas.

OBJECTIVE: To evaluate a multicentre series of robot-assisted partial nephrectomy (RAPN) performed for the treatment of large angiomyolipomas (AMLs). PATIENTS AND METHODS: Between 2005 and 2016, 40 patients with large or symptomatic AMLs underwent RAPN at five academic centres in the USA. Patient demographics, AML characteristics, operative and postoperative clinical outcomes were recorded and analysed. Surgical outcomes were compared between patients who underwent selective arterial embolisation (SAE) before RAPN and patients who did not undergo pre-RAPN SAE. RESULTS: The median (interquartile range [IQR]) tumour diameter was 7.2 (5-8.5) cm, and the median (IQR) nephrometry score was 9 (7-10). Six patients (15%) had a history of tuberous sclerosis and 11 (28%) had previously undergone SAE. The median (IQR) operative time and warm ischaemia time was 207 (180-231) and 22.5 (16-28) min, respectively. A non-clamping technique was used in eight (20%) patients. The median (IQR) estimated blood loss was 200 (100-245) mL, and four patients (10%) received blood transfusion postoperatively. One intraoperative complication occurred (2.5%), and seven postoperative complications occurred in six patients (15%). During a median (IQR) follow-up of 8 (1-15) months, none of the patients developed AML-related symptoms. The median estimated glomerular filtration rate preservation rate was 95%. There were no differences in operative or perioperative outcomes between patients who underwent SAE before RAPN and those who did not. CONCLUSIONS: Robot-assisted partial nephrectomy appears to be a safe primary or secondary (post-SAE) treatment for large AMLs, with a favourable perioperative morbidity profile and excellent functional preservation. Longer follow-up is required to fully evaluate therapeutic efficacy.

Next-generation Multi-target Stool DNA Panel Accurately Detects Colorectal Cancer and Advanced Precancerous Lesions.

The multi-target stool DNA (mt-sDNA) test screens for colorectal cancer by analyzing DNA methylation/mutation and hemoglobin markers to algorithmically derive a qualitative result. A new panel of highly discriminant candidate methylated DNA markers (MDM) was recently developed. Performance of the novel MDM panel, with hemoglobin, was evaluated in a simulated screening population using archived stool samples weighted to early-stage colorectal cancer and prospectively collected advanced precancerous lesions (APL). Marker selection study (MSS) and separate preliminary independent verification studies (VS) were conducted utilizing samples from multi-center, case-control studies. Sample processing included targeted MDM capture, bisulfite conversion, and MDM quantitation. Fecal hemoglobin was quantified using ELISA. Samples were stratified into 75%/25% training-testing sets; model outcomes were cross-validated 1,000 times. All laboratory operators were blinded. The MSS included 232 cases (120 colorectal cancer/112 APLs) and 490 controls. The VS featured 210 cases (112 colorectal cancer/98 APLs) and 567 controls; APLs were 86.7% adenomas and 13.3% sessile serrated lesions (SSL). Average age was 65.5 (cases) and 63.2 (controls) years. Mean sensitivity in the VS from cross-validation was 95.2% for colorectal cancer and 57.2% for APLs, with specificities of 89.8% (no CRC/APLs) and 92.4% (no neoplasia). Subgroup analyses showed colorectal cancer sensitivities of 93.4% (stage I) and 94.2% (stage II). APL sensitivity was 82.9% for high-grade dysplasia, 73.4% for villous lesions, 49.8% for tubular lesions, and 30.2% for SSLs. These data support high sensitivity and specificity for a next-generation mt-sDNA test panel. Further evaluation of assay performance will be characterized in a prospective, multi-center clinical validation study (NCT04144738). PREVENTION RELEVANCE: This study highlights performance of the next-generation mt-sDNA test, which exhibits high sensitivity and specificity for detecting colorectal cancer and APLs. This noninvasive option has potential to increase screening participation and clinical outcomes. A multi-center, clinical validation trial is underway. See related commentary by Bresalier, p. 93.

Benign mature teratoma of the cecum: a case report.

A teratoma is a typically benign tumor derived from more than one embryonic cell line, and it is characterized by presence of tissue foreign to the tumor location site. With the unlikely primary location in the gastrointestinal tract and no history of malignancy, we present a rare case of a primary mature cystic teratoma of the cecum. The patient is a 66-year-old male with imaging demonstrating an extraluminal, seemingly fat-containing mass abutting the cecum. The patient underwent resection, and final pathology revealed a mature cystic teratoma. Primary mature teratoma of the cecum is exceptionally rare; thus, diagnosis can be challenging. As he had no primary testicular or retroperitoneal mass, this cystic lesion likely represents a developmental abnormality and not a true neoplasm. The radiographic features, presentation, differential diagnoses, and treatment recommendations are discussed.

A Cross-Sectional Analysis of Factors Associated with Appointment Completion and Visit Modality during Virtual Urology Visits.

INTRODUCTION: The necessary transition to telehealth during COVID-19 generated new challenges for providers and patients, with the opportunity to exacerbate or mitigate standing care inequities. To better understand virtual medicine care delivery in urology, we sought to identify factors associated with appointment completion and use of telephone or video visits. METHODS: We performed a retrospective, single-institutional cross-sectional analysis of all remote patient appointments from March 17, 2020-August 31, 2020. The primary outcome was appointment completion rate. Patients were determined to have not completed an appointment if they canceled, left before being seen or were a "no show." Secondary analysis evaluated factors associated with scheduling video vs telephone appointment. Various patient and appointment-specific factors were analyzed. Chi-squared tests and univariate logistic regression were used for analysis accordingly. RESULTS: Of 3,769 appointments, 2,996 (79.5%) were completed while 773 (20.5%) were not, with 1,544 (41.0%) completed over telephone while 2,225 (59.0%) used video. Race, age, income, insurance, location, division and appointment length showed statistical significance (p <0.05) for appointment completion and visit modality. Females were more likely to use video (62.7% vs 58.0%, p=0.01). Patients were more likely to complete afternoon visits (81.1% vs 78.3%, p=0.04), visits with physicians (81.2% vs 75.4%, p <0.01) and phone calls (83.3% vs 76.9%, p <0.01). CONCLUSIONS: Multiple factors were associated with both appointment completion rate and use of telephone or video. These factors may reflect disparities in social determinants of health and select patients may benefit from additional coordination of care to prevent missed appointments and deconstruct inequities.

Pain management following robotic-assisted radical prostatectomy: transitioning to an opioid free regimen.

Few studies demonstrate the safety and efficacy of postoperative pain regimens that exclude opioids altogether in patients undergoing robot-assisted radical prostatectomy (RARP). To reduce opioid use, we sought to develop an opioid-free regimen for RARP and determine perioperative outcomes before and after implementation. A retrospective, pre-post-interventional study was performed at a single institution between 8/2018 and 10/2019. An opioid-free pain regimen was developed and instituted on 3/7/2019, and all patients received preoperative counseling regarding pain expectations and management. Postoperative pain score was the primary outcome. Secondary outcomes included postoperative opioid use, length of stay, adverse events and unplanned health encounters within 30 days of discharge. Pearson's chi-squared and Student's t-tests were performed on categorical and continuous variables, respectively. Multivariable analysis was performed to determine risk factors for postoperative opioid use in the opioid-free cohort. A total of 89 patients were included for analysis; consisting of 47 (53%) pre-intervention and 42 (47%) post-intervention patients. Baseline characteristics were similar between groups. A significantly lower proportion of patients in the post-intervention group were administered opioids postoperatively (5% vs 53%, p < 0.01), despite having similar postoperative pain scores (2.69 vs 3.11, p = 0.19) and length of stay (1.0 days vs 1.2 days, p = 0.07). The post-intervention group had a significantly lower rate of opioid discharge prescriptions (14% vs 96%, p < 0.01). The rate of ED visits (12% vs 15%, p = 0.68), pain-related phone calls (17% vs 19%, p = 0.76) or adverse events (19% vs 13%, p = 0.42) were similar between groups. Among the opioid-free group, older patients were less likely to be administered postoperative opioids (OR 0.84, p = 0.046). A structured opioid-free pain regimen following RARP is non-inferior compared to traditional opioid-based standard of care. Adoption of similar regimens can help address the ongoing opioid epidemic in the United States and future work is needed to apply these principles broadly.

CT scan for suspected acute abdominal process: impact of combinations of IV, oral, and rectal contrast.

BACKGROUND There are limited data available on the ability of computed tomography (CT) to accurately diagnose abdominopelvic pathology in acutely ill inpatients suspected of having an acute abdominal process. The purpose of this study was to evaluate the diagnostic accuracy of abdominal/pelvic CT with varying use of contrast agents in hospitalized patients. METHODS A retrospective review of all hospital inpatients (3/1/07-5/31/07) who underwent urgent or emergent abdominal/pelvic CT with any combination of contrast, intravenous (IV), oral, rectal, or unenhanced for a suspected acute abdominal process was performed. Data collected included demographics, combination of contrast used, CT diagnosis, time from CT scan to subsequent intervention, intervention type, and actual diagnosis of the acute abdominal process. Accuracy of CT was compared between enhanced and unenhanced imaging using Fisher's exact test. RESULTS A total of 661 patients were identified. Use of IV contrast alone was found in 54.2% of CT scans and was correct in 92.5% of cases. IV and oral contrast was used in 22.2% of CT scans and was 94.6% correct. Unenhanced imaging was performed in 16.2% and was correct in 92.5%. Oral contrast alone was used in 7.0% and was 93.5% correct. There was no significant difference in the ability to correctly diagnose a suspected acute abdominal process when enhanced CT imaging was compared to unenhanced (p > 0.05). CONCLUSIONS CT contrast administration in critically ill hospitalized patients is not necessary to accurately diagnose an acute abdominal process. Eliminating the use of contrast may improve patient comfort, decrease patient risk, and minimize financial cost.