Erdafitinib in BCG-treated high-risk non-muscle-invasive bladder cancer.

BACKGROUND: Treatment options are limited for patients with high-risk non-muscle-invasive bladder cancer (NMIBC) with disease recurrence after bacillus Calmette-Guérin (BCG) treatment and who are ineligible for/refuse radical cystectomy. FGFR alterations are commonly detected in NMIBC. We evaluated the activity of oral erdafitinib, a selective pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor, versus intravesical chemotherapy in patients with high-risk NMIBC and select FGFR3/2 alterations following recurrence after BCG treatment. PATIENTS AND METHODS: Patients aged ≥18 years with recurrent, BCG-treated, papillary-only high-risk NMIBC (high-grade Ta/T1) and select FGFR alterations refusing or ineligible for radical cystectomy were randomized to 6 mg daily oral erdafitinib or investigator's choice of intravesical chemotherapy (mitomycin C or gemcitabine). The primary endpoint was recurrence-free survival (RFS). The key secondary endpoint was safety. RESULTS: Study enrollment was discontinued due to slow accrual. Seventy-three patients were randomized 2 : 1 to erdafitinib (n = 49) and chemotherapy (n = 24). Median follow-up for RFS was 13.4 months for both groups. Median RFS was not reached for erdafitinib [95% confidence interval (CI) 16.9 months-not estimable] and was 11.6 months (95% CI 6.4-20.1 months) for chemotherapy, with an estimated hazard ratio of 0.28 (95% CI 0.1-0.6; nominal P value = 0.0008). In this population, safety results were generally consistent with known profiles for erdafitinib and chemotherapy. CONCLUSIONS: Erdafitinib prolonged RFS compared with intravesical chemotherapy in patients with papillary-only, high-risk NMIBC harboring FGFR alterations who had disease recurrence after BCG therapy and refused or were ineligible for radical cystectomy.

Concomitant CIS on TURBT does not impact oncological outcomes in patients treated with neoadjuvant or induction chemotherapy followed by radical cystectomy.

BACKGROUND: Cisplatin-based neoadjuvant chemotherapy (NAC) for muscle invasive bladder cancer improves all-cause and cancer specific survival. We aimed to evaluate whether the detection of carcinoma in situ (CIS) at the time of initial transurethral resection of bladder tumor (TURBT) has an oncological impact on the response to NAC prior to radical cystectomy. PATIENTS AND METHODS: Patients were identified retrospectively from 19 centers who received at least three cycles of NAC or induction chemotherapy for cT2-T4aN0-3M0 urothelial carcinoma of the bladder followed by radical cystectomy between 2000 and 2013. The primary and secondary outcomes were pathological response and overall survival, respectively. Multivariable analysis was performed to determine the independent predictive value of CIS on these outcomes. RESULTS: Of 1213 patients included in the analysis, 21.8% had concomitant CIS. Baseline clinical and pathologic characteristics of the 'CIS' versus 'no-CIS' groups were similar. The pathological response did not differ between the two arms when response was defined as pT0N0 (17.9% with CIS vs 21.9% without CIS; p = 0.16) which may indicate that patients with CIS may be less sensitive to NAC or ≤ pT1N0 (42.8% with CIS vs 37.8% without CIS; p = 0.15). On Cox regression model for overall survival for the cN0 cohort, the presence of CIS was not associated with survival (HR 0.86 (95% CI 0.63-1.18; p = 0.35). The presence of LVI (HR 1.41, 95% CI 1.01-1.96; p = 0.04), hydronephrosis (HR 1.63, 95% CI 1.23-2.16; p = 0.001) and use of chemotherapy other than ddMVAC (HR 0.57, 95% CI 0.34-0.94; p = 0.03) were associated with shorter overall survival. For the whole cohort, the presence of CIS was also not associated with survival (HR 1.05 (95% CI 0.82-1.35; p = 0.70). CONCLUSION: In this multicenter, real-world cohort, CIS status at TURBT did not affect pathologic response to neoadjuvant or induction chemotherapy. This study is limited by its retrospective nature as well as variability in chemotherapy regimens and surveillance regimens.

Esophageal tuberculosis: role of endoscopic ultrasound in diagnosis.

Esophageal involvement by tuberculosis is rare and is commonly secondary to mediastinal lymph nodal involvement. Endoscopic ultrasound (EUS) is a good modality for evaluation of both esophageal wall and mediastinal lymph nodes. The objectives were to study the role of EUS in diagnosing esophageal tuberculosis, to differentiate primary from secondary form, and to assess the response. Retrospective analysis of data over 7 years (i.e. from 2003 to 2009) was used. The study was set in a tertiary care referral institute and focused on patients diagnosed with esophageal tuberculosis. Interventions used included endoscopy, EUS, EUS-FNA (fine needle aspiration) followed by antituberculosis treatment. The main outcome measurements were symptoms, endoscopic features, EUS features, pathological yield, and response to treatment. There were 32 cases of esophageal tuberculosis. The primary symptom was dysphagia, and endoscopy showed ulcers in 18/32 (56.25%) and extrinsic bulge in 20/32 (62.5%) in middle one third of esophagus. EUS showed lymph nodes adjacent to esophageal pathology in all cases. Subcarinal region was the most common site of lymphadenopathy and they were matted, heterogeneous with predominantly hypoechoic center. Histopathology of endoscopic biopsy of ulcers and EUS-FNA of lymph nodes provided the diagnosis of tuberculosis in 27/32 (84.35%). All patients were treated with antitubercular treatment and showed good clinical, endoscopic and endosonographic response. This is a retrospective study, and PCR and culture for Mycobacterium tuberculosis were not done. Esophageal tuberculosis does not appear to be a primary disease and is most likely secondary to mediastinal nodal tuberculosis. A conglomerated mass of heterogeneous with predominantly hypoechoic lymph nodes with intervening hyperechoic strands and foci on EUS appears to be characteristic of mediastinal tuberculosis.

Nomogram Predicting Bladder Cancer-specific Mortality After Neoadjuvant Chemotherapy and Radical Cystectomy for Muscle-invasive Bladder Cancer: Results of an International Consortium.

BACKGROUND: Cisplatin-based neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC) is associated with improved overall and cancer-specific survival. The post-NAC pathological stage has previously been reported to be a major determinant of outcome. OBJECTIVE: To develop a postoperative nomogram for survival based on pathological and clinical parameters from an international consortium. DESIGN, SETTING, AND PARTICIPANTS: Between 2000 and 2015, 1866 patients with MIBC were treated at 19 institutions in the USA, Canada, and Europe. Analysis was limited to 640 patients with adequate follow-up who had received three or more cycles of NAC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: A nomogram for bladder cancer-specific mortality (BCSM) was developed by multivariable Cox regression analysis. Decision curve analysis was used to assess the model's clinical utility. RESULTS AND LIMITATIONS: A total of 640 patients were identified. Downstaging to non-MIBC (ypT1, ypTa, and ypTis) occurred in 271 patients (42 %), and 113 (17 %) achieved a complete response (ypT0N0). The 5-yr BCSM was 47.2 % (95 % confidence interval [CI]: 41.2-52.6 %). On multivariable analysis, covariates with a statistically significant association with BCSM were lymph node metastasis (hazard ratio [HR] 1.90 [95% CI: 1.4-2.6]; p < 0.001), positive surgical margins (HR 2.01 [95 % CI: 1.3-2.9]; p < 0.001), and pathological stage (with ypT0/Tis/Ta/T1 as reference: ypT2 [HR 2.77 {95 % CI: 1.7-4.6}; p < 0.001] and ypT3-4 [HR 5.9 {95 % CI: 3.8-9.3}; p < 0.001]). The area under the curve of the model predicting 5-yr BCSM after cross validation with 300 bootstraps was 75.4 % (95 % CI: 68.1-82.6 %). Decision curve analyses showed a modest net benefit for the use of the BCSM nomogram in the current cohort compared with the use of American Joint Committee on Cancer staging alone. Limitations include the retrospective study design and the lack of central pathology. CONCLUSIONS: We have developed and internally validated a nomogram predicting BCSM after NAC and radical cystectomy for MIBC. The nomogram will be useful for patient counseling and in the identification of patients at high risk for BCSM suitable for enrollment in clinical trials of adjuvant therapy. PATIENT SUMMARY: In this report, we looked at the outcomes of patients with muscle-invasive bladder cancer in a large multi-institutional population. We found that we can accurately predict death after radical surgical treatment in patients treated with chemotherapy before surgery. We conclude that the pathological report provides key factors for determining survival probability.

Real-time assessment of learning curve for robot-assisted laparoscopic prostatectomy.

INTRODUCTION: The learning curves analysed to date for robot-assisted laparoscopic prostatectomy are based on arbitrary cut-offs of the total cases. METHODS: We analysed a large dataset of robot-assisted laparoscopic prostatectomies from a single centre between 2008 and 2019 for assessment of the learning curve for perioperative outcomes with respect to time and individual cases. RESULTS: A total of 1,406 patients were evaluated, with mean operative time 198.08 minutes and mean console time 161.05 minutes. A plot of operative time and console time showed an initial decline followed by a near-constant phase. The inflection points were detected at 1,398 days (308th case) for operative time and 1,470 days (324th case) for console time, with a declining trend of 8.83 minutes and 7.07 minutes, respectively, per quarter-year (p<0.001). Mean estimated blood loss showed a 70.04% reduction between the start (214.76ml) and end (64.35ml) (p<0.001). The complication rate did not vary with respect to time (p=0.188) or the number of procedures (p=0.354). There was insufficient evidence to claim that the number of operations (p=0.326), D'Amico classification (p=0.114 for intermediate versus low; p=0.158 for high versus low) or time (p=0.114) was associated with the odds of positive surgical margins. CONCLUSIONS: It takes about 300 cases and nearly 4 years to standardise operative and console times, with a requirement of around 80 cases per annum for a single surgical team in the initial years to optimise the outcomes of robot-assisted laparoscopic prostatectomy.

The Lister AirSeal® port closure technique - Initial patient outcomes.

INTRODUCTION: The 12-mm AirSeal® port is widely used in robotically assisted laparoscopic prostatectomy due to its ability to maintain stable pneumoperitoneal pressures and smoke evacuation. However, it creates a potential risk of port site hernia. We have traditionally used EndoClose™ to perform full thickness closure of this port, but noted that patients experienced increased pain related to this procedure, which sometimes persisted for several months. Using the Da Vinci Si we performed peritoneal closure with 2-0 vicryl by switching the fourth arm to the right master controller. The external oblique sheath was closed outside with 1 Ethibond. MATERIALS AND METHODS: We performed this closure in 20 consecutive patients (group 1). Postoperative day 1, 2 and post-discharge telephone consultation pain scores (1-10) were recorded and compared with the previous 20 consecutive patients who had the EndoClose closure (group 2). RESULTS: We recorded an instructional video to enable reproduction of the new technique. The mean length of stay was 1.5 days for patients in group 1 and 1.9 days for those in group 2 (P = 0.04). There was no difference in operating time or average day 1 pain scores. Post-discharge follow-up call revealed 1 of 20 patients who had AirSeal port site pain in group 1 and 5 of 17 in group 2 (P = 0.04). Pain scores also tended to be higher for group 2. CONCLUSIONS: Our preliminary analysis of this novel technique to close the AirSeal port in two separate layers improves postoperative pain related to this port site.

New detection configuration for low activity levels of PET tracers during the analysis of plasma samples.

A new radio-HPLC detection system for measuring radioactivity in plasma samples during Positron Emission Tomography [PET] studies was developed. It is based on detecting both the positron and one of the annihilation photons. The system focused on improving the measurement of radioactivity concentrations on an unmetabolized positron emitting a radiopharmaceutical [PER] in the presence of its radioactive metabolites, all containing the same positron emitter. This paper presents a new detection configuration that improves the minimal detectible activity (MDA), simplify the measuring systems and reduces the error caused by the metabolites. The detector is based on a plastic scintillator and a BGO scintillation crystal, that produces different light output spectra for signal and noise events. By summing the positron and the annihilated photon light outputs, different spectra are obtained for the metabolite and for the parent compound tracer and for tracer marked by different positron emitting isotopes. This new detection system can improve quantitative analysis of plasma samples. The spectrum change provides up to a three-fold improvement in sensitivity compared to the currently used detection systems that measure only the annihilation coincidence events. Results showed that for 11C the MDA was improved by approximately 520%. Furthermore, it provides the additional advantage of reliability by providing a method for separating the signal and noise readings from the gross detector readout. Accurate reconstruction algorithm of the signal was achieved over a wide measuring range even when the signal was only 5% of the gross measurement.

The association of level of practical experience in transrectal ultrasonography guided prostate biopsy with its diagnostic outcome.

INTRODUCTION The diagnostic yield of transrectal ultrasonography (TRUS) guided prostate biopsy is influenced by many patient and procedure specific factors. However, the role of operator specific factors remains inadequately defined. This study investigated the association of diagnostic outcome of TRUS guided biopsy with operator skill level. METHODS This study looked at a consecutive cohort of 690 men undergoing their first extended pattern TRUS guided prostate biopsy by 27 operators over a 24-month period in a single institution. Logistic regression was used for statistical analysis. RESULTS Biopsies performed by consultants (odds ratio [OR]: 2.35, p=0.004) and senior trainees (OR: 2.37, p=0.002) in patients with prostate specific antigen levels of <10ng/ml were more likely to be positive than those performed by junior trainees (cancer detection rate 50.0%, 50.3% and 29.9% respectively). Furthermore, biopsies performed by junior trainees yielded a significantly higher proportion of prostate cancers with a Gleason score of ≥3+4 than those performed by senior trainees (OR: 2.11, p=0.031) and consultants (OR: 2.40, p=0.013) (81.4%, 67.5% and 64.6% respectively). No significant differences emerged between operator skill groups for complications, rebiopsy rates or the number of prostate cancers found during the follow-up period (median: 34 months) of patients with a negative biopsy. CONCLUSIONS Level of operator experience is associated with the diagnostic outcome of extended pattern TRUS guided biopsy. The findings of this study imply that case selection, self-audit and expert supervision for the duration of the learning curve should form the basis of biopsy training.

Bilateral obstruction of bilaterally duplicated collecting systems requiring upper and lower moiety drainage.

A 60-year-old woman with a history of breast cancer presented with bilateral obstruction of bilaterally duplicated renal collecting systems secondary to extrinsic compression from metastatic pelvic lymphadenopathy. Bilateral JJ ureteric stents were inserted, resulting in some improvement of renal function but a failure to normalise completely. Repeat computed tomography demonstrated bilateral duplex collecting systems with persisting obstruction of the undrained moieties. Selective puncture was performed to decompress the obstructed renal moieties for bilateral nephrostomy catheter insertion. This allowed renal function to improve sufficiently for the patient to be discharged and commence chemotherapy. This is the first reported case of bilaterally obstructed partially duplicated collecting systems and it illustrates the importance of recognising anatomical variants to tailor treatment appropriately. It also highlights the important relationship between urology and interventional radiology in the management of such complex patients.

Histological changes and neural elements in the posterior cruciate ligament in osteoarthritic knees.

PURPOSE: To evaluate histological changes and neural elements in 100 posterior cruciate ligaments (PCLs) in patients with osteoarthritis. METHODS: 100 PCLs were obtained from a consecutive series of 46 women and 16 men aged 49 to 91 (mean, 67) years who underwent primary PCL-retaining total knee replacement for osteoarthritis. Histology was examined using conventional light microscopy. The PCLs were graded histologically in terms of parallel orientation of collagen fibres, mucoid degeneration, inflammation, and haemosiderin deposition. Histological changes were graded as normal, mild degeneration, moderate degeneration, and severe degeneration. The neural elements were assessed using immunohistochemical staining for S100 protein and neurofilaments. The histopathologist was blinded to the age, gender, and clinical and radiological grades of osteoarthritis. RESULTS: One specimen was excluded from analysis owing to inadequate tissue. In the remaining 99 specimens, histology was normal in 72, mildly degenerative in 4, moderately degenerative in 4, and severely degenerative in 15. 76 specimens were positive for S100 protein or neurofilament or both by immunohistochemical staining, indicating the presence of neural elements. CONCLUSION: Most knees with osteoarthritis present with viable PCLs. Retaining the PCL in total knee replacement is a good option for better kinematics, stability, and proprioception.

Robotic Prostatectomy Has a Superior Outcome in Larger Prostates and PSA Density Is a Strong Predictor of Biochemical Recurrence.

Objectives. The aims of this study were to compare the outcomes of robotic assisted laparoscopic prostatectomy (RALP) between patients who had larger (≥75 g) and smaller (<75 g) prostates and to evaluate the performance of PSA density (PSAD) in determining the oncological outcome of surgery. Methods and Materials. 344 patients who underwent RALP at a single institution were included in the study. Preoperative risk factors and postoperative, oncological outcomes, erectile function, and continence status were recorded prospectively. Results. During a mean follow-up of 20 months, biochemical recurrence (PSA > 0.2) was observed in 15 patients (4.3%). Prostate size ≥75 g was associated with lower Gleason score on final pathology (P = 0.004) and lower pathological stage (P = 0.02) but an increased length of hospital stay (P = 0.05). PSAD on binary logistic regression independently predicted biochemical recurrence (BCR) when defined as postoperative PSA >0.1 (P = 0.001) and PSA >0.2 (P = 0.039). In both instances PSA was no longer a significant independent predictor. Conclusions. RALP in large prostates (≥75 g, <150 g) is as safe as RALP in smaller prostates and is associated with a lower pathological grade and stage. Higher PSAD is independently associated with BCR and is superior to PSA as a predictor of BCR after RALP.

Has the introduction of the '2 week rule' in the UK led to an earlier diagnosis of urological malignancy?

INTRODUCTION: The '2 week wait' target for haematuria assessment has been recommended for early diagnosis of urological cancer. We compare our cancer detection rates pre- and post-introduction of this target and its impact on stage at diagnosis. PATIENTS AND METHODS: A total of 1,740 patients were enrolled prospectively in the study at our units 'one stop fast track haematuria clinic' between April 2003 and March 2006. Evaluation consisted of basic demographics, history and examination, routine blood tests, urinalysis, urine culture and urine cytology. All patients underwent a renal ultrasound, IVU (intravenous urogram) and flexible cystoscopy. The detection rate of urological malignancy was compared to a previous cohort at our institution (April 1994 to March 1997). RESULTS: A total of 1,067 males and 673 females with a mean age of 60.8 years (range 16-96) were included in the study. The overall cancer detection rate was 18%. With the introduction of the '2 week rule' referrals, we noted a 57% increase in the detection of urological malignancies while comparing previous published data from our institution. There was no statistical significance in stage at presentation following the introduction of the '2 week rule'. CONCLUSION: Patients with haematuria need to be investigated promptly. The '2 week rule' has increased the cancer detection rate in our institution.

A review of current hemostatic agents and tissue sealants used in laparoscopic partial nephrectomy.

Laparoscopic partial nephrectomy (LPN) is currently considered to be one of the most challenging procedures in minimally invasive urological surgery. With an increasing number of renal tumors being managed using LPN, there is now a further interest in the development of techniques and agents to reduce complications associated with the procedure. Hemostasis is of paramount importance during LPN, and hemostatic agents and tissue sealants are now being used commonly during LPN. Despite this, there is a dearth of prospective, randomized, human trials in current literature that compare the various agents. This review evaluates hemostatic agents and tissue sealants being used during LPN as an adjuvant to suturing in human studies.