Loss of LPAR6 and CAB39L Dysregulates the Basal-To-Luminal Urothelial Differentiation Program, Contributing to Bladder Carcinogenesis

We describe a strategy that combines histologic and molecular mapping that permits interrogation of the chronology of changes associated with cancer development on a whole-organ scale. Using this approach, we present the sequence of alterations around RB1 in the development of bladder cancer. We show that RB1 is not involved in initial expansion of the preneoplastic clone. Instead, we found a set of contiguous genes that we term forerunner genes whose silencing is associated with the development of plaque-like field effects initiating carcinogenesis. Specifically, we identified five candidate forerunner genes (ITM2B, LPAR6, MLNR, CAB39L, and ARL11) mapping near RB1. Two of these genes, LPAR6 and CAB39L, are preferentially downregulated in the luminal and basal subtypes of bladder cancer, respectively. Their loss of function dysregulates urothelial differentiation, sensitizing the urothelium to N-butyl-N-(4-hydroxybutyl)nitrosamine-induced cancers, which recapitulate the luminal and basal subtypes of human bladder cancer

[35] The impact of the ’optimised surgical journey’ on robot-assisted radical prostatectomy patients: A prospective non-randomised longitudinal cohort study

Objective: To examine the impact of a standardised postoperative algorithm on robot-assisted radical prostatectomies (RARPs) performed at our centre in Kuwait. Prostate cancer is the most common cancer in Kuwaiti males since 2011 and after acquiring the Da Vinci® Si robot (Intuitive Surgical Inc., Sunnyvale, CA, USA) in 2013, a RARP programme was established. Methods: We collected data prospectively on all RARP cases performed since February 2014. We used the Clavien–Dindo system to grade complications, defining major complications as Clavien–Dindo Grade ⩾III. We examined recovery variables of all patients. We adopted a standardised postoperative algorithm called the ‘optimised surgical journey’ (OSJ) for managing RARP patients. Results: Between February 2014 and June 2018, a single surgeon’s robotic experience at Sabah Alahmad Urology Center (SAUC) included a total of 136 cases (116 cases done as the main console surgeon and 20 cases done with an invited robotic proctor). Of these, 53 cases (39%) were RARP (47 cases as the main console surgeon and six cases with an invited robotic proctor). The mean patient age was 62 years. The mean prostate volume was 50 mL. The mean estimated blood loss was 100 mL. Five patients had positive surgical margins (9%). The initial 12 RARPs were managed with non-standardised postoperative orders; the mean hospital stay was 4.83 days. Since April 2015, 41 patients underwent the OSJ protocol, reducing hospital stay by 2.57 days (P< 0.001). We report only one major complication (Clavien–Dindo Grade IIIb), where the patient had a prolonged leak requiring prolonged catheterisation and cystoscopy with cystogram under general anaesthesia, but no significant association with the OSJ. Conclusion: Standardised postoperative pathways improve recovery of patients undergoing major procedures like RARP. The OSJ decreased hospital stay without compromising surgical or oncological outcomes. Limitations are the small number of patients, lack of randomisation and possible impact of the learning curve on the initial cases

Non-seminomatous germ cell tumor with bone metastasis only at diagnosis: A rare clinical presentation

Bone metastasis of non-seminomatous germ cell tumors (NSGCT) of the testes is a rare event and even more uncommon at initial presentation. Generally, bone lesions are discovered in the presence of concurrent retroperitoneal lymph node or visceral disease. However, in this case, a 37 years old male complaining of a growing testicular mass was found to have isolated bone metastasis with associated caudaequina syndrome without apparent abnormal findings on initial computed tomography (CT) scans. Continued neurologic symptoms prompted further evaluation with magnetic resonance imaging (MRI), which demonstrated multiple sites of bone metastasis without evidence of retroperitoneal lymph node or visceral organ involvement. This case represents a rare clinical presentation and disease manifestation of NSGCT

Validation and Application of MD Anderson Symptom Inventory Module for Patients with Bladder Cancer in the Perioperative Setting

Objectives: We developed and validated a disease-specific tool for perioperative patient-reported outcomes assessment for bladder cancer (BLC) patients undergoing radical cystectomy, The MD Anderson Symptom Inventory (the MDASI-PeriOp-BLC). Methods: Patients who underwent radical cystectomy were recruited. We used qualitative interviews and experts&rsquo; input to generate disease/treatment-specific items of the MDASI-PeriOp-BLC module; conducted item reduction; examined the psychometric properties of the resultant items for reliability, validity, and clinical interpretability; and conducted cognitive debriefing interviews to assess the tool&rsquo;s performance. Results: A total of 150 BLC patients contributed to psychometric validation. We identified and defined eight BLC-specific module items (blood in urine, leaking urine, frequent urination, urinary urgency, burning with urination, constipation, changes in sexual function, and stomal problems). We included those 8 items in addition to 13 MDASI core symptoms and 6 interference items to form the MDASI-PeriOp-BLC module. Cronbach alphas were 0.89 and 0.90 for the 21 severity items and the 6 interference items, respectively. Test&ndash;retest reliability (intra-class correlation) was 0.92 for the 21 severity items. The MDASI-PeriOp-BLC module significantly differentiated the patients by performance status (p &lt; 0.0001). Conclusions: The MDASI-PeriOp-BLC is a valid, reliable, and concise tool for monitoring symptom burden during perioperative care in BLC patients undergoing radical cystectomy

High-intensity local treatment of clinical node-positive urothelial carcinoma of the bladder alongside systemic chemotherapy improves overall survival

PURPOSE: Clinical node-positive urothelial carcinoma of the bladder (cN+UCaB) is a rapidly fatal disease with limited information on comparative-effectiveness of available treatment options. We sought to examine the impact of high-intensity vs. conservative local treatment (LT) regimens in management of these patients alongside systemic chemotherapy. MATERIALS AND METHODS: We identified 3,227 patients within the National Cancer Data Base who underwent multiagent systemic chemotherapy along with either high-intensity or conservative LT for primary cN+UCaB between 2004-2016. Patients who received no LT, TURBT alone, or \u3c50 Gy radiation therapy to the bladder were included in the conservative group, while patients that received radical cystectomy with pelvic lymphadenectomy or ≥50 Gy radiation therapy with TURBT were included in the high-intensity group. Inverse probability of treatment weighting (IPTW) adjusted Kaplan-Meier and Cox regression analyses were used to assess overall survival (OS). Additionally, to assess whether the benefit of high-intensity LT differs by baseline mortality risk, we tested an interaction between 5-year predicted life-expectancy and the LT type. RESULTS: Overall, 784 (24.3%) and 2,443 (75.7%) cN+UCaB patients underwent high-intensity and conservative LT, respectively. IPTW-adjusted Kaplan-Meier analysis demonstrated OS to be significantly higher in the high-intensity group compared to the conservative group: 5-year OS 28.4% vs. 18.3%, respectively (Log-rank P\u3c0.001). IPTW-adjusted multivariable Cox regression analysis confirmed the benefit of high-intensity LT in prolonging OS (HR 0.63, P\u3c0.001). Interaction analysis showed that high-intensity LT approach was associated with longer OS in all patients regardless of their baseline 5-year life-expectancy (P(interaction)=0.79). CONCLUSION: Eligible patients with cN+UCaB should be considered for aggressive local treatment alongside multiagent systemic chemotherapy. Prospective trials are needed to validate these preliminary findings