Changes in the Perioperative Management and Outcomes of Patients With Upper Tract Urothelial Carcinoma Undergoing Radical Nephroureterectomy at Memorial Sloan Kettering Cancer Center: Over 20 Years of Experience.

INTRODUCTION: We evaluated surgical trends, perioperative management evolution, and oncologic outcomes in patients who underwent radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) at a tertiary cancer center over a 24-year period. METHODS: Between 1995 and 2018, we evaluated 743 consecutive patients with UTUC who underwent RNU. Generalized additive models were used to estimate the associations between date of surgery and continuous outcomes using a linear model, dichotomous outcomes using a logit link, categorical outcomes using multinomial models, and 2- and 5-year survival outcomes using Cox proportional hazards models. RESULTS: Over the study period, preoperative diagnostic endoscopic biopsies increased from 10% to 66%, along with the proportion of patients who underwent RNU for high-grade disease from 55% to 91%. The rate of open RNU declined from 100% to 56% with a rise in minimally invasive approaches. Median lymph node yield increased with more retroperitoneal lymph node dissections performed. Neoadjuvant chemotherapy utilization increased with a contemporary utilization rate of 32%, coinciding with an increase in pT0 rate from 2% to 8%. Cancer-specific survival probabilities improved over the study period, while metastasis-free and overall survival remained stable. CONCLUSIONS: We found several changes in treatment patterns and outcomes for patients with UTUC over the past 2 decades. How individual alterations in management factors, such as patient selection, perioperative chemotherapy, lymphadenectomy, and salvage therapies, impact patient outcomes is challenging in the setting of multiple overlapping practice changes for this rare disease and warrants further investigation.

Multicenter Phase II Clinical Trial of Gemcitabine and Cisplatin as Neoadjuvant Chemotherapy for Patients With High-Grade Upper Tract Urothelial Carcinoma.

PURPOSE: Neoadjuvant chemotherapy (NAC) has proven survival benefits for patients with invasive urothelial carcinoma of the bladder, yet its role for upper tract urothelial carcinoma (UTUC) remains undefined. We conducted a multicenter, single-arm, phase II trial of NAC with gemcitabine and split-dose cisplatin (GC) for patients with high-risk UTUC before extirpative surgery to evaluate response, survival, and tolerability. METHODS: Eligible patients with defined criteria for high-risk localized UTUC received four cycles of split-dose GC before surgical resection and lymph node dissection. The primary study end point was rate of pathologic response (defined as < ypT2N0). Secondary end points included progression-free survival (PFS), overall survival (OS), and safety and tolerability. RESULTS: Among 57 patients evaluated, 36 (63%) demonstrated pathologic response (95% CI, 49 to 76). A complete pathologic response (ypT0N0) was noted in 11 patients (19%). Fifty-one patients (89%) tolerated at least three complete cycles of split-dose GC, 27 patients (47%) tolerated four complete cycles, and all patients proceeded to surgery. With a median follow up of 3.1 years, 2- and 5-year PFS rates were 89% (95% CI, 81 to 98) and 72% (95% CI, 59 to 87), while 2- and 5-year OS rates were 93% (95% CI, 86 to 100) and 79% (95% CI, 67 to 94), respectively. Pathologic complete and partial responses were associated with improved PFS and OS compared with nonresponders (≥ ypT2N any; 2-year PFS 100% and 95% v 76%, P < .001; 2-year OS 100% and 100% v 80%, P < .001). CONCLUSION: NAC with split-dose GC for high-risk UTUC is a well-tolerated, effective therapy demonstrating evidence of pathologic response that is associated with favorable survival outcomes. Given that these survival outcomes are superior to historical series, these data support the use of NAC as a standard of care for high-risk UTUC, and split-dose GC is a viable option for NAC.

Testicular Cancer Knowledge and Viewpoints of American Men.

Introduction: We sought to better understand the baseline knowledge and practices of the general population regarding testicular cancer (TC) and testicular self-examination (TSE) in an effort to understand whether current screening guidelines reflect their viewpoint. The U.S. Preventive Services Task Force (USPSTF) currently recommends against TSE for TC screening due to a lack of data to support a benefit. Early detection of TC may reduce the required burden of therapy and associated long-term toxicities. Methods: This was a cross-sectional survey study. Participants (median age 33 years, IQR 28-39) were recruited via Amazon Mechanical Turk, a validated crowdsourcing platform used to recruit minimally compensated participants. Results: A total of 250 men rated themselves as "somewhat unknowledgeable" about TC, with no respondents considering themselves "very knowledgeable." Only 26.4% of men knew that TC was curable most of the time. Despite 90.8% of men feeling that their doctor had some role in discussing TC/TSE, only 17.2% had discussed these topics with their doctor. Even after being informed of the rationale behind USPSTF recommendations, only 8% of men thought that potential false positives of TSE would be more important than the rare chance of finding early TC. Conclusions: American men do not feel knowledgeable about TC, have a favorable attitude toward TSE and want their doctor to discuss these topics. Shared decision making regarding TC screening is warranted given the low risk of harm and patient interest, and continued accrual of data on this topic is necessary given the lack of prospective work to date.

Survival Impact of Variant Histology Diagnosis in Upper Tract Urothelial Carcinoma.

PURPOSE: Little is known regarding the prognostic implications of variant histology in upper tract urothelial carcinoma (UTUC). We sought to evaluate the impact of variant histology UTUC on patient survival outcomes at our institution. MATERIALS AND METHODS: We identified 705 patients who underwent nephroureterectomy for UTUC at our institution between January 1995 and December 2018. We tested the association between variant histology and cancer-specific survival (CSS) and overall survival (OS) using separate multivariable Cox models after adjusting for pathological stage. RESULTS: Forty-seven patients (6.7%) had variant histology, with prevalence increasing over time (p=0.003). Other demographic and surgical characteristics were similar between variant histology and pure urothelial carcinoma groups. While patients with variant histology were more likely to receive neoadjuvant chemotherapy (38% vs 15%, p <0.001), they were also more likely to have a higher pathological T stage (p <0.001). Variant histology was associated with significantly worse CSS (HR: 2.14; 95% CI 1.33, 3.44; p=0.002) and OS (HR: 1.74; 95% CI 1.15, 2.63; p=0.008). After adjusting for pathological T stage, variant histology was not significantly associated with CSS (HR: 1.17; 95% CI 0.72, 1.89; p=0.5) or OS (HR: 1.20; 95% CI 0.79, 1.84; p=0.4). CONCLUSIONS: Variant histology UTUC is associated with advanced stage and poor survival, and could serve as a useful biomarker for high-risk disease when pathological stage is unknown. However, the inferior CSS and OS with variant histology can be explained by the higher tumor stage on nephroureterectomy. Thus, finding variant histology on surgical pathology does not provide additional prognostic information beyond stage.

Isolated perinephric lymphoma: A distinct presentation of primary lymphoma.

Isolated perinephric lymphoma is a rare presentation of primary lymphoma. We report a case of a 77-year-old male who was incidentally found to have isolated left perinephric lymphoma. We outline the diagnostic work up and subsequent diagnosis of lymphoma as well as the considerations that guided management. Ultimately, bone marrow biopsy and PET-CT were used as diagnostic tools to assess for systemic disease and the patient was managed with observation and interval follow-up imaging.

Pathological and oncological outcomes in patients with sarcomatoid differentiation undergoing cystectomy.

OBJECTIVE: To evaluate whether urothelial carcinoma (UC) with sarcomatoid differentiation is associated with a lower pathological response rate to neoadjuvant chemotherapy (NAC) and worse oncological outcomes compared to UC without variant histology among patients undergoing radical cystectomy. PATIENTS AND METHODS: Patients with UC undergoing cystectomy from 1995 to 2018 at the Memorial Sloan Kettering Cancer Centre were identified. Patients with sarcomatoid differentiation at transurethral resection (TUR) or cystectomy, and patients without variant histology were selected. Downstaging from ≥cT2 to ≤pT1N0 defined partial response and pT0N0 defined complete response. Recurrence-free, cancer-specific and overall survival were modelled. RESULTS: We identified 131 patients with sarcomatoid differentiation and 1722 patients without variant histology, of whom 25 with sarcomatoid histology on biopsy and 313 without variant histology received NAC. Those with sarcomatoid differentiation presented with higher consensus tumour stage (94% ≥T2 vs 62%; P < 0.001) and were, therefore, more likely to receive NAC (29% vs 18%; P = 0.003). We found no evidence to support a difference in partial (24% vs 31%) or complete (20% vs 24%) response between patients with sarcomatoid histology and those with pure UC at TUR (P = 0.6). Among patients with sarcomatoid differentiation, 5-year recurrence-free survival was 55% (95% confidence interval [CI] 41-74) among patients receiving NAC and 40% (95% CI 31-52) among patients undergoing cystectomy alone (P = 0.1). Adjusting for stage, nodal involvement, margin status and receipt of NAC, sarcomatoid differentiation was associated with worse recurrence-free (hazard ratio [HR] 1.82, 95% CI 1.39-2.39), disease-specific (HR 1.66, 95% CI 1.23-2.22), and overall survival (HR 1.37, 95% CI 1.06-1.78). CONCLUSIONS: Sarcomatoid differentiation was associated with higher stage at presentation and independently associated with worse survival. Given similar pathological response rates if sarcomatoid differentiation is detected at initial resection, and greater survival among patients receiving NAC, treatment with NAC appears warranted. Other drivers of the poor outcomes of this histology must be investigated.

Rezum for retention-retrospective review of water vaporization therapy in the management of urinary retention in men with benign prostatic hyperplasia.

OBJECTIVE: Rezum vapor ablation is a minimally invasive treatment for benign prostatic hyperplasia (BPH) that uses injections of sterile water vapor directly into the prostate for tissue ablation. Although Rezum is currently indicated for use in men with prostate sizes ≥30 and ≤80 ml, it is unclear how effective Rezum is for men in urinary retention. We sought to determine whether Rezum is effective in the treatment of catheter-dependent urinary retention secondary to BPH. METHODS: A retrospective chart review was conducted on consecutive patients who presented for urinary retention and subsequently treated with Rezum. We evaluated procedural details and examined variables pre- and post-Rezum (at 6 months) including International Prostate Symptom Score (IPSS), IPSS quality of life (IPSS-QOL), maximum flow (Qmax ), post void residual volume (PVR), prostate specific antigen, rate of retention, and use of alpha blockers and 5-alpha reductase inhibitor (5ARI). RESULTS: Of the 49 patients included in this study, median age of was 73 years, median prostate volume was 73cc (Interquartile range [IQR]: 50, 103) and a median lobe was present in 80% of patients. All patients were in urinary retention before treatment with a median PVR of 900 ml (IQR: 566, 1146). Following Rezum, IPSS (17 pre-Rezum, 4 post-Rezum) and IPSS-QOL (4 pre-Rezum, 1 post-Rezum) both improved at 6 months (p < 0.01). Qmax increased from 3 to 6 ml/s (p = 0.03) and PVR decreased from 900 to 78 ml (p < 0.01). Only 17/38 patients taking alpha-blockers and 7/15 patients on 5ARIs continued therapy at 6 months following Rezum (p < 0.01). Of the 49 patients treated, 10 (20.4%) remained in catheter dependent urinary retention following the procedure, and 6 remained in retention at 6 months (12.2%) even after further surgical therapies for BPH (p < 0.01). CONCLUSION: Rezum is a safe and effective therapy for treating catheter dependent urinary retention in patients with BPH, including those with median lobes. As a minimally invasive therapy, it is a promising option in patient, particularly those who are not suitable for prolonged anesthesia.

Small lymphocytic lymphoma of the prostate mimicking a PIRADS 5 lesion that resolved after systemic treatment.

Prostatic PIRADS 4 and 5 lesions on multiparametric MRI typically represent adenocarcinoma with small lymphocytic lymphoma being a rare pathological finding. We report a case of small lymphocytic lymphoma masquerading as PIRADS 4 and 5 lesions with associated lymphadenopathy in a 69-year-old male on active surveillance for low-risk prostate cancer that was subsequently confirmed on targeted and systematic prostate biopsy. Following treatment of lymphoma with ibrutinib, there was complete resolution of the PIRADS lesions on follow-up mpMRI.

Functional and Oncological Outcomes of Renal Surgery for Hilar Tumors: Informing the Decisions in Risk-Adapted Management.

OBJECTIVE: To describe the safety and efficacy of partial nephrectomy (PN) in comparison to radical nephrectomy (RN) for surgically managed renal hilar tumors. MATERIALS AND METHODS: We retrospectively reviewed institutional records of patients with a small (<5 cm) solitary renal (hilar or non-hilar) mass who underwent PN or RN between 2008 and 2018. Hilar tumors were defined as those at medial position, abutting the renal vessels. Recurrence-free, cancer-specific, and overall survival were estimated using the Kaplan-Meier method. RESULTS: Of 1,951 eligible patients, 399 had hilar tumors (292 scheduled for PN, 107 RN) and 1,552 had non-hilar tumors (scheduled for PN). We found no significant differences in survival measures between hilar and non-hilar tumors in patients selected for PN. Patients scheduled for PN for hilar tumors had higher rates of ≥grade II postoperative surgical complications compared to patients scheduled to receive PN for non-hilar tumors (13% vs 8.6%; log-rank P = .018) and non-statistically significantly elevated rates of ≥grade II complications compared to patients scheduled for RN for hilar tumors (13% vs 6.5%; difference 6%, 95% CI 0.4%, 13%; log-rank P = .07). CONCLUSION: PN for hilar and non-hilar renal masses (<5cm) experience comparable oncologic outcomes though increased risk of complications for hilar masses. PN for hilar tumors was associated with better renal function and overall survival with non-statistically elevated risk of grade II or higher complications than RN. A renal tumor located at the hilum should not be a contra-indication for performing PN.

Review of Priapism Litigation in the United States.

OBJECTIVES: To review medical malpractice trends and to identify the most common claims filed against medical providers for the management of patients with priapism. METHODS: Using the Westlaw legal database, a search was done for the keyword "priapism" between July 1, 1980 and July 1, 2020. Cases were evaluated for plaintiff demographics, reasons for filing claims, management outcomes, legal verdicts and awards and further categorized based upon the timing of the alleged malpractice. RESULTS: Alleged negligence during the pre-management period was cited in 30 cases. Administration of psychotropic medications was the most common reasons for filing pre-management claims 22/56 (39.3%). Delay in care accounted for 18/56 (32.1%) and complications of surgery were 5/56 (8.9%) of claims. The majority of the completed cases were in favor of the defendants (39/47; 83.0%). There was no association between type of health care provider or timing of alleged malpractice and ultimate verdict. CONCLUSIONS: Prescribing psychoactive medications without warning of the adverse effect profile is the most common reason for claims filed against providers with trazodone as the leading medication. Medical providers should ensure that patients are well informed of this adverse effect prior to prescription. Regardless, the majority of medical malpractice cases carry a verdict in favor of the defendant.

Evolving case of emphysematous pyelonephritis in a second renal allograft.

Emphysematous pyelonephritis is an acute necrotizing infection with gas in the kidney that portends a poor prognosis. Patients present with sepsis, requiring fluid resuscitation, glucose control, and broad-spectrum antibiotics. Surgical intervention ranges from relief of urinary obstruction (nephrostomy tube or stent), percutaneous drainage or nephrectomy. We present a 51-year-old second kidney transplant recipient diabetic male, suffering from sepsis of unknown etiology which was subsequently revealed to be due to emphysematous pyelonephritis. Percutaneous drainage was performed initially followed by renal transplant nephrectomy after no improvement of his clinical status. Herein, we describe the clinical course and escalation in management.

Open partial nephrectomy with kidney split: Effective surgical approach to resect completely endophytic tumors.

OBJECTIVES: To review perioperative, renal functional, and oncological outcomes of the kidney split technique in performing partial nephrectomy (PN) to resect completely endophytic renal tumors. METHODS: All consecutive patients who underwent open PN with kidney split between 2015 and 2019 at our institution were included. In this approach the kidney is incised along Brodel's line in an avascular plane to locate and then resect the endophytic tumor. Clinicopathologic data, perioperative metrics, complications, renal function, recurrence, and mortality were analyzed using descriptive statistics. RESULTS: Forty-two open PN with kidney split were performed in 40 patients. No patients required conversion to radical nephrectomy. Most tumors were pT1a renal cell carcinoma (76%), with no recurrences or deaths after a median follow-up of 15 months. All patients had tumors of moderate or high complexity by R.E.N.A.L. nephrometry score. Median cold ischemia time, operative time, estimated blood loss, and inpatient length-of-stay were 34 minutes, 152 minutes, 225 ml, and 2 days, respectively. No patients experienced any Clavien-Dindo grade 4 or 5 complications. Postoperative estimated glomerular filtration rate (eGFR) at last follow-up was >30 ml/min/1.73m2 in all but one patient, and no patients required dialysis. CONCLUSIONS: The kidney split represents an effective PN technique to resect complex, endophytic renal tumors. In our experience, this technique affords acceptable perioperative outcomes, preserved renal function, and no short-term recurrences or mortality events. Our series highlights the importance of adapting classical surgical techniques, using cold ischemia, and relying on preoperative and intraoperative ultrasonography to effectively guide this complex kidney-sparing operation.

Inguinal hernia of the distal ureter causing hydronephrosis: A rare case.

Ureteral involvement in inguinal hernias is a rare occurrence. A 63-year-old man presented for surveillance of renal cell carcinoma with new onset mild intermittent flank pain. CT scan revealed new left hydroureteronephrosis to the level of the inguinal canal with dilated segments of ureter within an inguinal hernia. The patient underwent robot-assisted laparoscopic left ureterolysis and hernia repair. Ureter-containing inguinal hernias represent an uncommon but important source of obstructive uropathy. When encountered, robotic hernia repair provides a safe and effective treatment option.

Germ Cell Tumor Molecular Heterogeneity Revealed Through Analysis of Primary and Metastasis Pairs.

PURPOSE: Although primary germ cell tumors (GCTs) have been extensively characterized, molecular analysis of metastatic sites has been limited. We performed whole-exome sequencing and targeted next-generation sequencing on paired primary and metastatic GCT samples in a patient cohort enriched for cisplatin-resistant disease. PATIENTS AND METHODS: Tissue sequencing was performed on 100 tumor specimens from 50 patients with metastatic GCT, and sequencing of plasma cell-free DNA was performed for a subset of patients. RESULTS: The mutational landscape of primary and metastatic pairs from GCT patients was highly discordant (68% of all somatic mutations were discordant). Whereas genome duplication was common and highly concordant between primary and metastatic samples, only 25% of primary-metastasis pairs had ≥ 50% concordance at the level of DNA copy number alterations (CNAs). Evolutionary-based analyses revealed that most mutations arose after CNAs at the respective loci in both primary and metastatic samples, with oncogenic mutations enriched in the set of early-occurring mutations versus variants of unknown significance (VUSs). TP53 pathway alterations were identified in nine cisplatin-resistant patients and had the highest degree of concordance in primary and metastatic specimens, consistent with their association with this treatment-resistant phenotype. CONCLUSION: Analysis of paired primary and metastatic GCT specimens revealed significant molecular heterogeneity for both CNAs and somatic mutations. Among loci demonstrating serial genetic evolution, most somatic mutations arose after CNAs, but oncogenic mutations were enriched in the set of early-occurring mutations as compared with VUSs. Alterations in TP53 were clonal when present and shared among primary-metastasis pairs.

Surveillance post-radiofrequency ablation for small renal masses: Recurrence and followup.

INTRODUCTION: Small renal masses (SRMs), enhancing tumors <4 cm in diameter, are suspicious for renal cell carcinoma (RCC). The incidence of SRMs have risen with the increased quality and frequency of imaging. Partial nephrectomy is widely accepted as a nephron-sparing approach for the management of clinically localized RCC, with a greater than 90% disease-specific survival for stage T1a. Radiofrequency ablation (RFA) has been emerging as an alternative management strategy, with evidence suggesting RFA as a safe alternative for SRMs. We aimed to evaluate the time to recurrence and recurrence rates of SRMs treated with RFA at our institution. METHODS: A retrospective review between October 2011 and May 2019 identified 141 patients with a single SRM treated with RFA at Hamilton Health Sciences and St. Joseph's Healthcare Hamilton. Patients with familial syndromes and distant metastases were excluded. Repeat RFAs of the ipsilateral kidney for incomplete ablation were not considered a new procedure. The primary variable measured was time from initial ablation to recurrence. A Cox proportional hazard regression model was used to identify possible prognostic variables for tumor recurrence defined a priori, including age, gender, mass size, RENAL nephrometry, and PADUA scores. RESULTS: The overall average age of our patients was 69.0±11.1 years, with 71.6% being male. Average tumor size was 2.6±0.8 cm. There were 22/154 total recurrences (15.6%) post-RFA. Median followup time was 67 (18-161) months. Those with new recurrences had median time to recurrence of 15 months and no recurrence beyond 53 months. Thirteen of 141 patients had residual disease (9.2%) and were identified within the first eight months post-RFA. The only prognostic variable identified as a predictor of residual disease was tumor size (hazard ratio 2.265; p<0.001). CONCLUSIONS: This study shows the risk of a new recurrence following RFA for SRMs is 6.4%. Most recurrences (9.2%) were a result of residual tumor at the ablation site identified within the first eight months post-RFA. No recurrences were identified beyond 53 months, with a total median followup time of 67 months. Tumor size alone, without need for complex scoring systems, may serve as a predictor of incomplete ablation following RFA and could be used to assist in shared decision-making on management strategies.

Utility of Routine Preoperative 18F-Fluorodeoxyglucose Positron Emission Tomography/Computerized Tomography in Identifying Pathological Lymph Node Metastases at Radical Cystectomy.

PURPOSE: We determined the diagnostic performance of 18F-FDG (fluorodeoxyglucose) positron emission tomography/computerized tomography for detecting nodal metastases in patients with muscle invasive urothelial bladder cancer before radical cystectomy. MATERIALS AND METHODS: Preoperative 18F-FDG positron emission tomography/computerized tomography scans (208) were retrospectively reviewed. Scans were routinely performed in 185 patients with muscle invasive urothelial bladder cancer between August 2012 and February 2017, all of whom underwent radical cystectomy and pelvic lymph node dissection. Analyses were stratified by clinical node involvement and chemotherapy status. The diagnostic performance of 18F-FDG positron emission tomography/computerized tomography was assessed according to sensitivity, specificity, positive predictive value and negative predictive value. RESULTS: Lymph node metastases at time of pelvic lymph node dissection were present in 21.8% of those without suspicious nodes on computerized tomography (clinically node negative) and 52.6% of those with suspicious nodes on computerized tomography (clinically node positive). Median metastatic focus size was 5 mm. In clinically node negative cases 18F-FDG positron emission tomography/computerized tomography rarely detected nodal metastases (sensitivity 7% to 23%). In clinically node positive cases negative 18F-FDG positron emission tomography/computerized tomography was useful in ruling out lymph node metastases (sensitivity 92% to 100%). This study was limited by its mixed population and focus on pelvic nodal metastases only. CONCLUSIONS: 18F-FDG positron emission tomography/computerized tomography appears to be most useful for better characterization of enlarged nodes identified by computerized tomography. Routine preoperative 18F-FDG positron emission tomography/computerized tomography has limited utility in clinically node negative cases.

Off- vs. On-Pump Coronary Artery Bypass Grafting Long-Term Survival is Driven by Incompleteness of Revascularisation.

BACKGROUND: Off-pump coronary artery bypass grafting (CABG) negates the requirement for extracorporeal circulation used with the traditional on-pump approach. However, off-pump CABG is technically more challenging and may theoretically lead to less complete revascularisation. Recent data suggests a prognostic benefit for traditional on-pump CABG, but the mechanism for this remains unclear. We hypothesised that the inferior outcomes with off-pump CABG could be driven by the need for repeat revascularisation, with this benefit only becoming clear at long-term follow-up. We therefore evaluated short, medium and long-term outcomes of patients undergoing revascularisation with on vs. off-pump CABG. METHODS: Electronic databases were searched to identify suitable randomised controlled trials enrolling ≥100 patients in each arm. Clinical outcomes were extracted at 30-days, 12-months or >4years. The primary outcome was long-term all-cause death, while secondary outcomes included 30-day, 12-month and >4-year cardiac death, stroke, myocardial infarction or revascularisation. RESULTS: Thirteen (13) studies comprising 13,234 patients were included. Off-pump CABG was associated with an increased risk of all-cause death (Odds Ratio [OR] 1.18, 95% confidence interval [CI] 1.02-1.32, p=0.01) and repeat bypass surgery (OR 2.57, 95%CI 1.23-5.39, p=0.01) at long-term follow-up. A significant, increased requirement for revascularisation in off-pump was seen at 12-month follow-up (OR 1.59, 95%CI 1.09-2.33, p=0.02). No differences were noted between groups at 30-days, 12-months and >4years for myocardial infarction or stroke. CONCLUSIONS: Off-pump CABG is associated with significantly higher rates of all-cause mortality rate at long-term follow-up. These outcomes demonstrate a temporal relationship that may be driven by a greater requirement for repeat revascularisation at 1- and 5-year follow-up. STUDY REGISTRATION: CRD42018102019 (PROSPERO).

The potential risk of tumor progression after use of dehydrated human amnion/chorion membrane allograft in a positive margin resection model.

OBJECTIVE: The objective of this study was to examine the impact of dehydrated human amnion/chorion membrane (dHACM) allografts on prostate and bladder cancer growth in the setting of residual disease and positive surgical margins. MATERIALS AND METHODS: A commercially available version of dHACM was used. Cytokines were identified and quantified, followed by comparative analysis of cell growth in two different human cell lines: prostate cancer (LNCaP) and bladder cancer (UM-UC-3), in vitro and in vivo. Tumor growth between the two groups, membrane versus no membrane implant, was compared and immunohistochemistry studies were conducted to quantify CD-31, Ki-67, and vimentin. A Student's unpaired t-test was used to determine statistical significance. RESULTS: The UM-UC-3 and LNCaP cells grew quicker in medium plus 10% serum and dHACM extract than in the other media (p = 0.03). A total of 28 distinct cytokines were found in the extract, 11 of which had relatively high concentrations and are associated with prostate and bladder cancer tumor progression. In vivo LNCaP model, after 10 weeks, the median tumor volume in the membrane group was almost threefold larger than the partial resection alone (p = 0.01). Two weeks after resection, in the UM-UC-3 model, the membrane group reached fourfold larger than the partial resection without membrane group (p < 0.01). In both groups, the expression of CD-31 and Ki-67 markers were similar and showed no statistical significance (p > 0.05). It was only in the LNCaP tumors that vimentin expression was significantly higher in the group without membrane compared with the membrane group (p = 0.008). CONCLUSION: The use of dHACM after partial tumor resection is related to faster tumor relapse and growth in prostate and urothelial cancer in vivo models, showing a potential risk of rapid local recurrence in patients at high risk of positive margins.