The value of a comprehensive primary outcome - results of a negative randomized control trial in the non-muscle invasive bladder cancer population.

INTRODUCTION American Urological Association (AUA) guidelines recommend intravesical chemotherapy to be given following transurethral resection of a bladder tumor. Prior studies have shown the benefit of mitomycin as well as gemcitabine. However, no study has compared the two agents. MATERIALS AND METHODS: The study was designed as an open label 1:1:1 randomized controlled trial, comparing intravesical mitomycin, gemcitabine and saline as a single intraoperative instillation immediately following transurethral resection of suspected bladder tumor. Primary endpoint was any grade ≥ 3 events according to NCI CTCAE Version 4.03, this captures any return trip to the operating room for recurrence of cancer or other event (benign bladder/urethra). Secondary endpoints were progression free survival for urothelial cell carcinoma and adverse events. RESULTS: A total of 82 patients were enrolled and randomized, unfortunately the trial was suspended early due to protocol deviations. In an intention to treat analysis, freedom from grade > 3 events at 2 years was 74.8% in the no treatment arm, 51.0% in the mitomycin arm, and 56.0% in the gemcitabine arm (p = 0.81). Freedom from cancer recurrence for all patients was 62.3%. In the no treatment arm, it was 78.8%, and 50.7% and 63.6% in the mitomycin arm and gemcitabine arm respectively. (p = 0.28). In a univariate analysis, the only patient variable significantly associated with the primary outcome was pathologic T stage (p < 0.002). CONCLUSION: This study provides an example of a novel, patient centered primary outcome with the goal of determining which treatment paradigms provide the greatest oncologic and clinic benefit.

Transumbilical laparoendoscopic single-site surgery in urology.

Laparoendoscopic single-site surgery has seen a dramatic rise in the urological community. With the advent of new techniques and instrumentation, laparoendoscopic single-site surgery has become more accessible for a wide variety of applications. The majority have been carried out through a transumbilical incision in order to effectively hide the scar within the umbilicus. Here, we review the history and clinical applications for transumbilical laparoendoscopic single-site surgery within urology. The current scope is broad, and great strides have been made, but the overall benefit appears to be predominantly cosmetic. Diffusion of laparoendoscopic single-site surgery techniques from tertiary referral centers to the community urologist remains unknown. This review demonstrates the feasibility of transumbilical laparoendoscopic single-site surgery as shown in the urological literature.

Management of prostate cancer after holmium laser enucleation of the prostate.

INTRODUCTION: Holmium laser enucleation of the prostate (HoLEP) is effective in treating lower urinary tract symptoms from prostatic disease. We investigate the role of HoLEP in the management of patients with benign prostatic hypertrophy (BPH) and prostate cancer (CaP). METHODS: Retrospective review of data regarding all patients undergoing HoLEP at a single institution was performed. Pre- and postoperative PSA, multiparametric MRI, and pathology results were analyzed for those with CaP identified prior to or incidentally at HoLEP. RESULTS: From February 2016 to February 2020, 201 patients underwent HoLEP. Twelve patients had CaP diagnosed before HoLEP: 6 patients with GG1 are on active surveillance (AS), 3 of 4 intermediate-risk patients are on AS and 1 received treatment for disease progression, and both high-risk CaP patients achieved symptomatic benefit from HoLEP and are receiving systemic therapy for CaP. Twenty-one patients (11.1%) with incidentally detected CaP at HoLEP remain on AS or watchful waiting based on clinical scenario. CONCLUSION: Screening for CaP in HoLEP candidates with PSA and MRI is recommended given that >10% will have incidental CaP. After HoLEP for BPH/LUTS, patients with CaP can be surveilled with PSA and/or MRI. Further investigation is warranted to determine the durability of success of these approaches.

Early and late perioperative outcomes following radical cystectomy: 90-day readmissions, morbidity and mortality in a contemporary series.

PURPOSE: Radical cystectomy remains associated with significant morbidity. Most series report outcomes with relatively short-term followup that may underestimate the true magnitude of the procedure and many report length of hospital stay but ignore readmission rates. We analyzed the predictors of early (30 days or less), late (31 to 90 days) and cumulative 90-day hospital readmissions, as well as morbidity and mortality rates. MATERIALS AND METHODS: We reviewed our prospectively collected database of 753 patients who underwent radical cystectomy for urothelial cancer between January 2001 and December 2007. We examined the relationship between clinical variables and readmission rates during the early, late and 90-day postoperative period, and reviewed mortality and perioperative morbidity rates. RESULTS: There were 200 (26.6%) patients readmitted in the first 90 days following radical cystectomy. Of these patients 148 (19.7%) were readmitted early, 81 (10.8%) were readmitted late, and 29 (3.9%) had an early and late readmission. Logistical regression revealed gender (OR 1.50, 95% CI 1.00-2.27, p = 0.05), age adjusted Charlson comorbidity index (OR 1.19, 95% CI 1.06-1.34, p = 0.003) and any postoperative complications before discharge home (OR 1.84, 95% CI 1.19-2.83, p = 0.006) as independent predictors of 90-day readmission. The 30 and 90-day mortality rates were 2.1% (16) and 6.9% (52), respectively. CONCLUSIONS: Readmission rates after radical cystectomy are significant, approaching 27% within the first 90 days. Gender and age adjusted Charlson comorbidity index were independent predictors providing preoperative information identifying patients more likely to require readmission or possibly to benefit from a longer initial hospital stay.

Preoperative hydronephrosis predicts extravesical and node positive disease in patients undergoing cystectomy for bladder cancer.

PURPOSE: Preoperative hydronephrosis may be associated with a worse outcome in patients who undergo radical cystectomy for invasive bladder cancer. We characterized the prognostic significance of hydronephrosis, and its relationship to cancer stage and outcome. We also evaluated concordance between the side of identifiable hydronephrosis and concomitant pelvic lymph node metastasis. MATERIALS AND METHODS: We analyzed information from our prospectively collected database of patients who underwent radical cystectomy for bladder cancer from January 2001 to December 2007. We examined the relationship between hydronephrosis and clinical variables as well as survival outcome. Hydronephrosis was diagnosed intraoperatively or by radiographic imaging within 3 months of radical cystectomy. RESULTS: Of 753 patients 244 (32%) were diagnosed with hydronephrosis. Logistic regression modeling revealed that hydronephrosis was an independent predictor of extravesical disease (OR 2.01, 95% CI 1.37 to 2.96, p <0.001) and node positive disease (OR 1.94, 95% CI 1.29 to 2.91, p = 0.001). Of patients with hydronephrosis 88 (36.1%) had concomitant node positive disease and 74 (30.3%) had node positive disease on the same side as hydronephrosis. Thus, hydronephrosis predicted the side of nodal involvement in 74 of 88 patients (84%) with identifiable hydronephrosis and node positive disease. CONCLUSIONS: Hydronephrosis is an independent predictor of advanced bladder cancer stage, and it predicts extravesical disease and node positive disease. Thus, it could prove useful to select patients for neoadjuvant chemotherapy before surgery. The strong correlation between hydronephrosis side and nodal metastasis may have implications for surgical staging and approach.

Endovascular Removal of Intracardiac Thrombus Prior to Radical Nephrectomy and Inferior Vena Cava Thrombectomy.

We report a case of a 54-year-old patient with a T3c renal mass with intracardiac extension of the thrombus to the level of the pulmonary valve. The patient was not a candidate for cardiopulmonary bypass due to recent pulmonary embolism. Under transesophageal echocardiogram guidance, the intracardiac thrombus was removed percutaneously via transvenous mechanical thrombectomy. The patient was effectively downstaged to T3b and underwent successful radical nephrectomy and inferior vena cava thrombectomy without the use of cardiopulmonary bypass.

Pharmacologic disruption of TRPV1-expressing primary sensory neurons but not genetic deletion of TRPV1 protects mice against pancreatitis.

OBJECTIVES: Transient receptor potential subtype vanilloid 1 (TRPV1) is an ion channel that is primarily expressed by primary sensory neurons where it mediates pain and heat sensation and participates in neurogenic inflammation. In this study, we examined the role of TRPV1 during neurogenic activation of pancreatic inflammation using a secretagogue-induced model in mice. METHODS: A supramaximal dose of caerulein (50 microg/kg) was injected hourly for 12 hours. Mice lacking TRPV1 were compared to wild-type animals. RESULTS: All the parameters: serum amylase, pancreatic myeloperoxidase activity, histological scoring, pancreatic wet weight/body weight ratio, and quantification of neurokinin-1 receptor internalization indicated that null mice were not protected from acute pancreatitis. However, when primary sensory neurons were ablated by injection of the neurotoxin and TRPV1 agonist, resiniferatoxin, pancreatitis was ameliorated in wild-type mice but not in null mice, indicating that nerves bearing TRPV1 are part of the inflammatory pathway in acute pancreatitis because disappearance significantly reduced the inflammatory response. CONCLUSIONS: Nerves expressing TRPV1 participate in the neurogenic inflammation during acute pancreatitis. The lack of protection in TRPV1 null mice suggests that an alternate pathway to TRPV1 coexists in the same neurons.

Local disruption of the celiac ganglion inhibits substance P release and ameliorates caerulein-induced pancreatitis in rats.

Primary sensory neurons of the C and Adelta subtypes express the vanilloid capsaicin receptor TRPV1 and contain proinflammatory peptides such as substance P (SP) that mediate neurogenic inflammation. Pancreatic injury stimulates these neurons causing the release of SP in the pancreas resulting in pancreatic edema and neutrophil infiltration that contributes to pancreatitis. Axons of primary sensory neurons innervating the pancreas course through the celiac ganglion. We hypothesized that disruption of the celiac ganglion by surgical excision or inhibition of C and Adelta fibers through blockade of TRPV1 would reduce the severity of experimental pancreatitis by inhibiting neurogenic inflammation. Resiniferatoxin (RTX) is a specific TRPV1 agonist that, in high doses, selectively destroys C and Adelta fibers. Sprague-Dawley rats underwent surgical ganglionectomy or application of 10 microg RTX (vs. vehicle alone) to the celiac ganglion. One week later, pancreatitis was induced by six hourly intraperitoneal injections of caerulein (50 microg/kg). The severity of pancreatitis was assessed by serum amylase, pancreatic edema, and pancreatic myeloperoxidase (MPO) activity. SP receptor (neurokinin-1 receptor, NK-1R) internalization in acinar cells, used as an index of endogenous SP release, was assessed by immunocytochemical quantification of NK-1R endocytosis. Caerulein administration caused significant increases in pancreatic edema, serum amylase, MPO activity, and NK-1R internalization. RTX treatment and ganglionectomy significantly reduced pancreatic edema by 46% (P < 0.001) and NK-1R internalization by 80% and 51% (P < 0.001 and P < 0.05, respectively). RTX administration also significantly reduced MPO activity by 47% (P < 0.05). Neither treatment affected serum amylase, consistent with a direct effect of caerulein. These results demonstrate that disruption of or local application of RTX to the celiac ganglion inhibits SP release in the pancreas and reduces the severity of acute secretagogue-induced pancreatitis. It is possible that selectively disrupting TRPV1-bearing neurons could be used to reduce pancreatitis severity.