Comparing different pneumoperitoneum (12 vs. 15 mmHg) pressures with cytokine analysis to evaluate clinical outcomes in patients undergoing robotic-assisted laparoscopic radical cystectomy and intracorporeal robotic urinary diversion.

Background: Robotic cystectomy is the mainstay surgical intervention for treatment-refractory nonmuscle-invasive and muscle-invasive bladder cancer. However, paralytic ileus may complicate the postoperative recovery and may be a consequence of an inflammatory response associated with transient gut ischaemia. We have therefore investigated clinical, operative and inflammatory biomarker associations between paralytic ileus in the context of robotic cystectomy and intracorporeal ileal conduit urinary diversion. Methods: Prospective consective patients referred for robotic cystectomy were consented and included in the study, while patients >75 years old and converted to open procedure were excluded. The pneumoperitoneum pressure (PP) for carbon dioxide insufflation required to perform the procedure efficiently and safely was recorded (12 or 15 mmHg). We also recorded the postoperative days patients passed flatus and stools, whether they developed ileus, as well as other standard clinical and demographic data. The expression of select proinflammatory and anti-inflammatory cytokines was determined by multiplex analysis using a cytometric bead array with changes in profiles correlated with the pressures applied and with the existence of an ileus. Results: Twenty-seven patients were recruited, but only 20 were used in the study with 10 patients in each PP group. Seven patients were excluded all of whom had an extracorporeal ileal conduit formation. There were differences in the 40-min shorter operative time and 1 day shorter length of stay, as well as passing flatus 1 day and stools 1.5 days earlier in the 12 mmHg compared with the 15 mmHg group. More patients had ileus in the 15 mmHg group vs 12 mmHg group (30% vs. 10.0%). These were not statistically significant. Similarly, there were no statistical differences in the expression of proinflammatory cytokines at the two different pressures or between patient groups, but there were outliers, with the median indicating nonsymmetrical distribution. By comparison, anti-inflammatory cytokines showed some significant differences between groups, with IL-6 and IL-10 showing elevated levels postsurgery. No statistical difference was observed between pressures or the existence of an ileus, but the maximum levels of IL-6 and IL-10 detected in some patients reflect a pressure difference. Conclusions: The initial findings of this novel scientific study indicated a higher risk of paralytic ileus postrobotic cystectomy and robotic intracorporeal urinary diversion when a higher pressure of 15 mmHg is used compared with 12 mmHg. Although further studies are required to establish the linkage between cytokine profile expression, pressure and ileus, our initial data reinforces the advantages of lower pressure robotic cystectomy and intracorporeal urinary diversion in patient outcomes.

Blue light transurethral resection and biopsy of bladder cancer with hexaminolevulinate: Histopathological characteristics and recurrence rates in a single UK centre study.

Introduction: Blue light cystoscopy with hexaminolevulinate (HAL) during transurethral resection of bladder cancer (TURBT) has been shown to improve detection, thereby reducing bladder cancer recurrence compared with white light cystoscopy. Methods: Single-centred UK (United Kingdom) study on 101 patients who underwent blue light cystoscopy between July 2017 and November 2020, performed by a single surgeon. Our study was divided into two arms; the primary arm had no prior diagnosis of bladder malignancy (N = 41), whereas secondary re-resection arm had (N = 57). Three patients with non-urothelial bladder cancer were excluded. Patients were followed up for 24 months. Data were collected on biopsy quality, histopathological characteristics and recurrence. The end points of the study were recurrence rate at 24 months in both arms and detection of CIS in patients who undergo TURBT or biopsy after initial white light study in the secondary, re-resection arm. This was analysed with Fisher's exact test. Results: Of 98 patients, 39 had malignancy in their first blue light TURBT/biopsy: primary arm (10/41, 24.4%) and secondary arm (29/57, 50.9%), with detrusor present in 80.5% and 80.7%, respectively. In the secondary arm, blue light re-resection TURBT detected significantly more CIS (20.7% vs 51.7%, p = 0.0277) compared with white light with 3.4% upstaged to muscle invasive bladder cancer (G3pT2). Median time to re-resection was 3.06 months. Recurrence rate was 33.3% in the primary arm and 37.5% in the secondary arm after 24 months of follow-up. Conclusion: Our data confirm that blue light TURBT with HAL provides superior detection and diagnosis of CIS in patients with previous white light cystoscopy.

Serum cytokine levels as markers of paralytic ileus following robotic radical prostatectomy at different pneumoperitoneum pressures.

BACKGROUND: To evaluate intraoperative and postoperative cytokines in patients who underwent robotic prostatectomy (RP) at a pressure of 12 or 15 mm Hg, and the risk of postoperative ileus. MATERIALS AND METHODS: We presented the first series evaluating intraoperative and postoperative cytokines in patients undergoing RP at a pressure of 12 or 15 mm Hg by a single surgeon. Changes in cytokine concentrations were shown to correlate with surgical outcomes and pathological states. The study investigated the changes in cytokine concentrations (interferon-γ, tumor necrosis factor-α, interleukin-1ß [IL-1ß], IL-2, IL-4, IL-6, IL-12, and IL-17) at different pneumoperitoneum pressures and their potential role in the development of postoperative ileus. RESULTS: The data on 10 consecutive patients confirmed that a lower pneumoperitoneum pressure was associated with lower cytokine levels and a lower risk of ileus. There were increased levels of postoperative interferon-γ, tumor necrosis factor-α, IL-12p70, IL-1ß, IL-2, IL-4, and IL-17a at 15 mm Hg when compared to 12 mm Hg. CONCLUSIONS: The data indicated that lower pressure RP reduced intra-/postoperative cytokine levels confirming our hypothesis. Larger patient numbers are required to further validate this but the implications of this data will benefit not only urological patients but also other speciality patients undergoing minimally invasive surgery.

The role of URO17™ biomarker to enhance diagnosis of urothelial cancer in new hematuria patients-First European Data.

Introduction and objectives: Novel biomarker research is vital for the progression of safe and thorough diagnostic medicine. There is now a need to improve the diagnosis of bladder cancer via a noninvasive urine test while balancing the risks of harm from investigational procedures, such as cystoscopy and radiological tests, against the likelihood of malignancy. We evaluate the diagnostic accuracy and sensitivity of Uro17™ urinary biomarker for the detection of urothelial cancer in hematuria patients in a prospective blinded validation study. Uro17™ is an immunobiomarker which binds to the oncoprotein Keratin 17, which is involved in the replication cycle of malignant cells. This study compared cystoscopic and histological investigations against Uro17™ results in patients being investigated for symptoms of urothelial cancer. Materials and methods: After receiving both local and national ethics/protocol approval, 71 patients were consented and recruited into the study. All patients were scheduled to undergo cystoscopic investigation, and following recruitment, a urine sample was collected. Urine samples were anonymized and processed as per standard cytology protocols and stained using Uro17™ immunobiomarker. The pathologists assessing the results were blinded to the patient and background history, and the results were compared to the biopsy histology. Results: The full cohort of enrolled patients consisted of 71 participants included. There were 55 males and 16 females, with an average age of 70. Thirteen were current smokers, 42 ex-smokers, and 16 nonsmokers. The malignancies detected included both muscle-invasive (n = 6) and non-muscle-invasive tumors (n = 38), and tumors of all grades and carcinoma in situ. Uro17™ was shown to have an overall sensitivity of 100% and a specificity of 92.6%, with a positive predictive value of 0.957 and negative predictive value of 1. Uro17™ investigation was positive in every case of urothelial malignancy. Conclusions: Our current data indicates Uro17™ is a highly sensitive noninvasive bladder cancer urine detection test that can improve the diagnosis of Bladder cancer. This can further improve diagnostic capabilities in primary care, reduce the number of referrals to Urology department, and reduce the number of unnecessary invasive procedures for new patients with a suspected urinary bladder cancer.

Radical Cystectomy in England from 2013 to 2019 on 12,644 patients: An analysis of national trends and comparison of surgical approaches using Hospital Episode Statistics data.

Introduction: We evaluate the data of 12,644 Radical Cystectomies in England (Open, Robotic and Laparoscopic) with trends in the adaption of techniques and post-operative complications. Methods: This analysis utilised national Hospital Episode Statistics (HES) from NHS England. Results: There was a statistically significant increase (P < .001) in the number of Robotic assisted radical cystectomies from 10.8% in 2013-2014 and 39.5% in 2018-2019.The average LOS reduced from 12.3 to 10.8 days for RARC from 2013 to 2019 similarly the LOS reduced from 16.2 to 14.3 for ORC. The rate of sepsis (0-90 days) did rise from 5% to 14.5% between 2013-2014 and 2017-2018 for the entire cohort (P < .001). Acute renal failure (ARF) increased over the years from 9.5% to 17% (P < .001). The rate for fever, UTI, critical care activity and ARF were higher for ORC than RARC (P < .001).The comparison of all episodes within 90 days for conduit versus non-conduit diversions showed significantly higher rates of sepsis, infections, UTI and fever in non-conduit group .Overall complications were significantly higher in non-conduit group throughout the duration except was year 2016-17(P < .001).The robotic approach has increased in last 5 years with nearly 40% of the cystectomies now being robotically in 2018-19 from the initial percentage of 10.8% in 2013-14. Conclusion: This evaluation of the HES data from NHS England for 12,644 RC confirms an increase in the adoption of Robotic Cystectomy. Our data confirms the need to develop strategies with enhanced recovery protocols and post-operative close monitoring following Radical Cystectomy in order to reduce post-operative complications.

Is Non-Chlamydial Non-Gonococcal Urethritis Associated with Significant Clinical Complications in Men? A Systematic Review.

BACKGROUND: It is estimated that between 50 and 89% of non-gonococcal urethritis is not caused by Chlamydia trachomatis. Associations between non-chlamydial non-gonococcal urethritis (NCNGU) with balanoposthitis, epididymo-orchitis and reactive arthritis have been suggested, but evidence to support these often-theoretical relationships is sparse and further investigation is called for. Concerns over increasing antimicrobial resistance has rendered the need for clarity over this question ever more pressing in recent years. A review of the current evidence on the complications of NCNGU in men is therefore urgently warranted. OBJECTIVE: This systematic review summarizes and evaluates the available evidence that NCNGU, whether symptomatic or asymptomatic, causes the significant complications that are already well-recognized to be associated with non-gonococcal urethritis. These significant complications are epididymo-orchitis, balanoposthitis, and sexually-acquired reactive arthritis (Reiter's syndrome) including arthritis or conjunctivitis. SUMMARY: We conducted a systematic review and qualitative synthesis using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis framework. Five databases (PubMed, EMBASE, Cumulative Index to Nursing and Allied Health Literature, PsycINFO, and British Nursing Index) were searched. We included studies that measured clinical outcome after diagnosis of NCNGU in men. Bias was assessed using variations of the Newcastle-Ottawa scale. Data were extracted and entered into a pre-written data abstraction proforma. Seven peer-review studies were included. This included 2 retrospective cohort studies, 1 case series, 2 case reports and 2 cross-sectional studies. The studies described and analyzed 3 types of complication: balanitis, posthitis and/or meatitis; reactive arthritis and/or conjunctivitis; and epididymitis. All studies reported one or more complications. KEY MESSAGES: This review identifies an important avenue for future research: while the available evidence suggests that NCNGU has the potential to cause significant complications in men, with the strongest evidence existing for balanitis, posthitis and/or meatitis, the nature and significance of these relationships is far from clear. The findings of this review suggest that prospective, adequately powered research into whether there is a causal link between NCNGU and significant clinical complications in men would be highly worthwhile. The findings of this review raise important questions about the utility of the term NCNGU in research and clinical practice.

A Comparison of Urology Training Across Five Major English-Speaking Countries.

BACKGROUND: Urology is a rapidly evolving specialty, although wide variations exist between training programs in different countries. We aimed to compare the status of urology training in 5 English-speaking countries. MATERIALS AND METHODS: Features compared include the training pathway structure, training requirements, competition levels and the process of moving country for international medical graduates. RESULTS: Length of training varied considerably across countries, ranging from 5 years in the USA and Canada, to 7 years in Australia and New Zealand and 9 years in the UK. Ease of entering urology training for international medical graduates also varies, with the UK relatively easier compared to other countries. All countries encourage participation in research during training as well as completion of non-urology and urology specific surgical examinations. CONCLUSION: Following the Royal College of Surgeons Improving Surgical Training report, it is vital that the UK incorporates optimal elements of international programs in order to provide the best standards for trainees and world-class care in urology.

The role of extended venous thromboembolism prophylaxis for major urological cancer operations.

OBJECTIVES: Venous thromboembolism (VTE), consisting of both pulmonary embolism (PE) and deep vein thromboses (DVT), remains a well-recognised complication of major urological cancer surgery. Several international guidelines recommend extended thromboprophylaxis (ETP) with LMWH, whereby the period of delivery is extended to the post-discharge period, where the majority of VTE occurs. In this literature review we investigate whether ETP should be indicated for all patients undergoing major urological cancer surgery, as well procedure specific data that may influence a clinician's decision. METHODS: We performed a search of six databases (PubMed, Cochrane, EMBASE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO, and British Nursing Index (BNI)) from inception to June 2019, for studies looking at adult patients who received VTE prophylaxis after surgery for a major urological malignancy. RESULTS: Eighteen studies were analysed. VTE risk is highest in open and robotic Radical Cystectomy (RC) (2.6-11.6%) and ETP demonstrates a significant reduction in risk of VTE, but not a significant difference in Pulmonary Embolism (PE) or mortality. Risk of VTE in open Radical Prostatectomy (RP) (0.8-15.7%) is comparable to RC, but robotic RP (0.2-0.9%), open partial/radical nephrectomy (1.0-4.4%) and robotic partial/radical nephrectomy (0.7-3.9%) were lower risk. It has not been shown that ETP reduces VTE risk specifically for RP or nephrectomy. CONCLUSION: The decision to use ETP is a fine balance between variables such as VTE incidence, bleeding risk and perioperative morbidity/mortality. This balance should be assessed for each specific procedure type. While ETP still remains of net benefit for open RP as well as open and robotic RC, the balance is closer for minimally invasive RP as well as radical and partial nephrectomy. Due to a lack of procedure specific evidence for the use of ETP, adherence with national guidelines remains poor. Therefore, we advocate further studies directly comparing ETP vs standard prophylaxis, for specific procedure types, in order to allow clinicians to make a more informed decision in future.