Achieving Benchmarks for National Quality Indicators Reduces Recurrence and Progression in Non-muscle-invasive Bladder Cancer.

BACKGROUND: Noncompliance with evidence-based interventions and guidelines contributes to significant and variable recurrence and progression in patients with non-muscle-invasive bladder cancer (NMIBC). The implementation of a quality performance indicator (QPI) programme in Scotland's National Health Service (NHS) aimed to improve cancer outcomes and reduce nationwide variance. OBJECTIVE: To evaluate the effect of hospitals achieving benchmarks for two specific QPIs on time to recurrence and progression in NMIBC. DESIGN, SETTING, AND PARTICIPANTS: QPIs for bladder cancer (BC) were enforced nationally in April 2014. NHS health boards collected prospective data on all new BC patients. Prospectively recorded surveillance data were pooled from 12 collaborating centres. INTERVENTION: QPIs of interest were (1) hospitals achieving detrusor muscle (DM) sampling target at initial transurethral resection of bladder tumour (TURBT) and (2) use of single instillation of mitomycin C after TURBT (SI-MMC). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary and secondary endpoints were time to recurrence and progression, respectively. Kaplan-Meier and Cox multivariable regression analyses were performed. KEY FINDINGS AND LIMITATIONS: Between April 1, 2014 and March 31, 2017, we diagnosed 3899 patients with new BC, of which 2688 were NMIBC . With a median follow up of 60.3 mo, hospitals achieving the DM sampling target had a 5.4% lower recurrence rate at 5 yr than hospitals not achieving this target (442/1136 [38.9%] vs 677/1528 [44.3%], 95% confidence interval [CI] = 1.6-9.2, p = 0.005). SI-MMC was associated with a 20.4% lower recurrence rate (634/1791 [35.4%] vs 469/840 [55.8%], 95% CI = 16.4-24.5, p < 0.001). On Cox multivariable regression, meeting the DM target and SI-MMC were associated with significant improvement in recurrence (hazard ratio [HR] 0.81, 95% CI = 0.73-0.91, p = 0.0002 and HR 0.66, 95% CI = 0.59-0.74, p < 0.004, respectively) as well as progression-free survival (HR 0.62, 95% CI = 0.45-0.84, p = 0.002 and HR 0.65, 95% CI = 0.49-0.87, p = 0.004, respectively). We did not have a national multicentre pre-QPI control. CONCLUSIONS: Within a national QPI programme, meeting targets for sampling DM and SI-MMC in the real world were independently associated with delays to recurrence and progression in NMIBC patients. PATIENT SUMMARY: Following the first 3 yr of implementing a novel quality performance indicator programme in Scotland, we evaluated compliance and outcomes in non-muscle-invasive bladder cancer. In 2688 patients followed up for 5 yr, we found that achieving targets for sampling detrusor muscle and the single instillation of mitomycin C during and after transurethral resection of bladder tumour, respectively, were associated with delays in cancer recurrence and progression.

Multiparametric ultrasound versus multiparametric MRI to diagnose prostate cancer (CADMUS): a prospective, multicentre, paired-cohort, confirmatory study.

BACKGROUND: Multiparametric MRI of the prostate followed by targeted biopsy is recommended for patients at risk of prostate cancer. However, multiparametric ultrasound is more readily available than multiparametric MRI. Data from paired-cohort validation studies and randomised, controlled trials support the use of multiparametric MRI, whereas the evidence for individual ultrasound methods and multiparametric ultrasound is only derived from case series. We aimed to establish the overall agreement between multiparametric ultrasound and multiparametric MRI to diagnose clinically significant prostate cancer. METHODS: We conducted a prospective, multicentre, paired-cohort, confirmatory study in seven hospitals in the UK. Patients at risk of prostate cancer, aged 18 years or older, with an elevated prostate-specific antigen concentration or abnormal findings on digital rectal examination underwent both multiparametric ultrasound and multiparametric MRI. Multiparametric ultrasound consisted of B-mode, colour Doppler, real-time elastography, and contrast-enhanced ultrasound. Multiparametric MRI included high-resolution T2-weighted images, diffusion-weighted imaging (dedicated high B 1400 s/mm2 or 2000 s/mm2 and apparent diffusion coefficient map), and dynamic contrast-enhanced axial T1-weighted images. Patients with positive findings on multiparametric ultrasound or multiparametric MRI underwent targeted biopsies but were masked to their test results. If both tests yielded positive findings, the order of targeting at biopsy was randomly assigned (1:1) using stratified (according to centre only) block randomisation with randomly varying block sizes. The co-primary endpoints were the proportion of positive lesions on, and agreement between, multiparametric MRI and multiparametric ultrasound in identifying suspicious lesions (Likert score of ≥3), and detection of clinically significant cancer (defined as a Gleason score of ≥4 + 3 in any area or a maximum cancer core length of ≥6 mm of any grade [PROMIS definition 1]) in those patients who underwent a biopsy. Adverse events were defined according to Good Clinical Practice and trial regulatory guidelines. The trial is registered on ISRCTN, 38541912, and ClinicalTrials.gov, NCT02712684, with recruitment and follow-up completed. FINDINGS: Between March 15, 2016, and Nov 7, 2019, 370 eligible patients were enrolled; 306 patients completed both multiparametric ultrasound and multiparametric MRI and 257 underwent a prostate biopsy. Multiparametric ultrasound was positive in 272 (89% [95% CI 85-92]) of 306 patients and multiparametric MRI was positive in 238 patients (78% [73-82]; difference 11·1% [95% CI 5·1-17·1]). Positive test agreement was 73·2% (95% CI 67·9-78·1; κ=0·06 [95% CI -0·56 to 0·17]). Any cancer was detected in 133 (52% [95% CI 45·5-58]) of 257 patients, with 83 (32% [26-38]) of 257 being clinically significant by PROMIS definition 1. Each test alone would result in multiparametric ultrasound detecting PROMIS definition 1 cancer in 66 (26% [95% CI 21-32]) of 257 patients who had biopsies and multiparametric MRI detecting it in 77 (30% [24-36]; difference -4·3% [95% CI -8·3% to -0·3]). Combining both tests detected 83 (32% [95% CI 27-38]) of 257 clinically significant cancers as per PROMIS definition 1; of these 83 cancers, six (7% [95% CI 3-15]) were detected exclusively with multiparametric ultrasound, and 17 (20% [12-31]) were exclusively detected by multiparametric MRI (agreement 91·1% [95% CI 86·9-94·2]; κ=0·78 [95% CI 0·69-0·86]). No serious adverse events were related to trial activity. INTERPRETATION: Multiparametric ultrasound detected 4·3% fewer clinically significant prostate cancers than multiparametric MRI, but it would lead to 11·1% more patients being referred for a biopsy. Multiparametric ultrasound could be an alternative to multiparametric MRI as a first test for patients at risk of prostate cancer, particularly if multiparametric MRI cannot be carried out. Both imaging tests missed clinically significant cancers detected by the other, so the use of both would increase the detection of clinically significant prostate cancers compared with using each test alone. FUNDING: The Jon Moulton Charity Trust, Prostate Cancer UK, and UCLH Charity and Barts Charity.

Concomitant Cholecystectomy for Asymptomatic Gallstones in Bariatric Surgery-Safety Profile and Feasibility in a Large Tertiary Referral Bariatric Center.

BACKGROUND: Obesity is a risk factor for gallstone formation, which can be exacerbated by bariatric surgery-induced rapid weight loss. Current guidelines do not recommend concomitant cholecystectomy (CC) for asymptomatic gallstones during the bariatric surgery procedure. However, long-term follow-up studies have shown that the incidence of post-bariatric surgery symptomatic gallstones necessitating therapeutic cholecystectomy increases to 40%. Therefore, some surgeons advocate simultaneous cholecystectomy during the bariatric surgery for asymptomatic individuals. This study aims to evaluate the safety of performing cholecystectomy for asymptomatic gallstones during the bariatric procedure. METHODS: Data from a consecutive series of patients that underwent primary laparoscopic sleeve gastrectomy (LSG), laparoscopic Roux-en-Y gastric bypass (LRYGB) or conversion of LSG to a LRYGB with or without concomitant cholecystectomy for asymptomatic gallstones between Jan 2010 and Dec 2017 were retrieved from the database. The primary endpoint was the complication rate. Secondary endpoints were the surgical operating room time (ORT) and the length of hospital stay (LOS). RESULTS: Out of the 2828 patients who were included, 120 patients underwent a concomitant cholecystectomy during their bariatric procedure (LSG or LRYGB) for asymptomatic gallbladder stones and were compared to the 2708 remaining patients who only had bariatric surgery. None of the concomitant cholecystectomy patients developed a gallbladder-related complication. There was no significant increase in the rate of minor or major complications between the CC groups and the non-CC groups (LSG: 6.7% vs. 3.2%, p=0.132; LRYGB: 0% vs. 2.3%, p =0.55; and conversion of LSG to LRYGB: 20% vs. 7.1%, p = 0.125, respectively). In addition, there was no significant increase in the length of hospital stay (1.85 ±4.19 days vs. 2.24 ±1.82, p=0.404) for LSG group and (1.75 ±2.0 vs. 2.3 ±2.1, p=0.179) for LRYGB group. Adding the cholecystectomy to the bariatric procedure only added an average of 23 min (min) (27 min when added to LSG and 18 min when added to LRYGB). CONCLUSION: As one of the largest series reviewing concomitant cholecystectomy in bariatric surgery, this study showed that in skilled laparoscopic bariatric surgical hands, concomitant cholecystectomy during bariatric surgery is safe and prevents potential future gallstone-related complications. Long-term large prospective randomized trials are needed to further clarify the recommendation of prophylactic concomitant cholecystectomy during bariatric surgery.

Contralateral traumatic carotid cavernous fistula after a craniomaxillofacial fracture.

INTRODUCTION: Carotid-cavernous fistula is an abnormal communication between the internal carotid artery, the external carotid artery or any of their branches and the cavernous sinus. This condition may occur spontaneously or after craniofacial trauma; in this case the fistula takes place on the same side as the craniofacial fracture and becomes symptomatic within a few weeks. The diagnosis is clinical; it must be evoked before any post-traumatic proptosis. Treatment must be started quickly to avoid visual or even vital complications. CASE PRESENTATION: We report the case of a 19 years old male patient who was admitted to the maxillofacial surgery department for osteosynthesis of a fracture of the left orbital roof after a traffic accident. The three-month's examination noted a right pulsatile proptosis with redness and decrease of the visual acuity. The cerebral MRI was in favor of a right sided direct CCF, which was confirmed by the arteriographie. The patient responded very well to embolization. DISCUSSION: Craniofacial trauma is a major cause of carotid cavernous fistula. When a patient has ophthalmic manifestations of vascular complications, early detection of CCF is important for preserving visual acuity. The diagnosis is mainly clinical based on the ophthalmological symptoms. CT and MRI scans show the indirect signs of the fistula. There are several types of invasive and non-invasive treatments. The evolution of the fistula is generally favorable and recurrence is not very frequent. CONCLUSION: This case report is a documentation on an exceptional case of posttraumatic direct CCF occurring on the contralateral side of the skull base fracture.

Lingual primary tuberculosis mimicking malignancy.

INTRODUCTION: The constant increase in the incidence of tuberculosis, as long as the emerging global resistance to antituberculous drugs warrants an increased awareness of the possibility of Mycobacterium Tuberculosis in persistent lesions of the oral cavity. Lingual tuberculosis is a rarely described entity of extra pulmonary tuberculosis. It usually presents as a non-healing chronic mucosal lesion that may mimic malignant lingual neoplasms. CASE REPORT: In the present paper, we report a rare presentation of lingual tuberculosis in a 36 years old woman, which was clinically suspected as an extensive malignant fissure of the tongue. The diagnosis was confirmed by tongue biopsy and the patient responded well to the antitubercular chemotherapy. DISCUSSION: lingual tuberculosis is a rare clinical and pathological entity of extrapulmonary tuberculosis. Only a few cases have been reported around the world, and in each one of them, a unique clinical form has been described. This variability of clinical presentations can allude to several pathological conditions including malignancy. CONCLUSION: This case report is a documentation of a unique clinical and radiological presentation of lingual tuberculosis; it also highlights the importance of considering tuberculosis in the differential diagnosis of chronic tongue lesions.

Testicular Pain Pathway in Children: Investigating Where Missed Torsion Occurs Most Often.

OBJECTIVES: Acute scrotal pain in children is a common presenting complaint in hospital, and it is imperative that cases of testicular torsion are identified and managed promptly. We aim to identify the most influential points in the pathway in determining whether patients are managed in the appropriate time frame, so these areas can be targeted to improve salvage rates. METHODS: Using quality improvement principles, the pediatric scrotal pain pathway was mapped out, commencing with initial symptom onset and ending with definitive surgical management. We retrospectively reviewed data on all patients between 0 and 18 years of age attending the emergency department at Whipps Cross University Hospital with acute scrotal pain between October 2010 and October 2013. RESULTS: Over the 3-year period, 238 patients 18 years or younger presented to casualty with scrotal pain. Of the patients assessed initially by an emergency department physician, 52.8% (n = 67) were discharged without referral. To our knowledge, none of these patients presented later with a missed torsion. Torsion was diagnosed in 23.2% of the patients operated on (n = 22), of which 5 required orchidectomy, comprising 2.1% of all patients presenting with scrotal pain. In this group, 4 were due to late presentation by the patient. CONCLUSIONS: We demonstrate the value of different stages of the pathway, as more than half of patients seen in A&E were correctly discharged without referral. In the context of our study, late presentation to hospital appears to be the most significant factor leading to orchidectomy. To target this issue, awareness among both children and parents must be improved.

Enhanced Quality and Effectiveness of Transurethral Resection of Bladder Tumour in Non-muscle-invasive Bladder Cancer: A Multicentre Real-world Experience from Scotland's Quality Performance Indicators Programme.

BACKGROUND: Clinical outcomes from non-muscle-invasive bladder cancer (NMIBC) are partly determined by the quality of initial interventions. To improve and standardise treatment for cancer, Scotland implemented a national Quality Performance Indicator (QPI) programme for bladder cancer (BC). OBJECTIVE: To evaluate compliance with specific quality indicators (QIs) related to transurethral resection of bladder tumour (TURBT) and to understand clinical outcomes from NMIBC following the introduction of the QPI programme. DESIGN, SETTING, AND PARTICIPANTS: Within a robust governance framework, 12 mandatory evidence-based QPIs were implemented nationally in April 2014. We report prospectively collected data for all new BC patients (between April 2014 and March 2017). We include follow-up data for 2689 patients. INTERVENTION: The TURBT-related QPIs were (1) using a bladder diagram, (2) single post-TURBT instillation of mitomycin C (SPI-MMC), (3) detrusor muscle (DM) in the specimen, and (4) early re-TURBT in high-risk NMIBC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We measured compliance with these QPIs and (1) recurrence rate at first follow-up cystoscopy (RRFFC), (2) rates of residual cancer, and (3) pT2 cancer at re-TURBT. Associations between QPI compliance, tumour features, and outcomes were assessed with multivariable logistic regression models. RESULTS AND LIMITATIONS: Among 4246 new BC patients, SPI-MMC was used in 67% (2029/3023) NMIBC patients. In 1860 NMIBC patients undergoing TURBT, RRFFC, rate of residual cancer, and rate of pT2 at re-TURBT were 13% (116/888), 33% (212/653), and 2.9% (19/653), respectively. SPI-MMC was associated with lower RRFFC, independent of all variables including hospital volume and surgeon. Presence of DM in the specimen halved the likelihood of residual disease in pT1 cancers. The main limitation is the lack of a pre-QPI introduction cohort for comparison. CONCLUSIONS: The implementation of a QI programme in Scotland appears to facilitate high-quality TURBT, which in a real-world setting is associated with low early recurrence/residual cancer and accurate pathological staging. PATIENT SUMMARY: Following the first 3 yr of implementing a novel Quality Performance Indicator (QPI) programme in Scotland, we assessed compliance and outcomes in non-muscle-invasive bladder cancer. Evaluating over 4000 new bladder cancer patients, we found that the QPI programme was associated with low recurrence and accurate staging following the initial transurethral resection of bladder tumour.

The SmartTarget Biopsy Trial: A Prospective, Within-person Randomised, Blinded Trial Comparing the Accuracy of Visual-registration and Magnetic Resonance Imaging/Ultrasound Image-fusion Targeted Biopsies for Prostate Cancer Risk Stratification.

BACKGROUND: Multiparametric magnetic resonance imaging (mpMRI)-targeted prostate biopsies can improve detection of clinically significant prostate cancer and decrease the overdetection of insignificant cancers. It is unknown whether visual-registration targeting is sufficient or augmentation with image-fusion software is needed. OBJECTIVE: To assess concordance between the two methods. DESIGN, SETTING, AND PARTICIPANTS: We conducted a blinded, within-person randomised, paired validating clinical trial. From 2014 to 2016, 141 men who had undergone a prior (positive or negative) transrectal ultrasound biopsy and had a discrete lesion on mpMRI (score 3-5) requiring targeted transperineal biopsy were enrolled at a UK academic hospital; 129 underwent both biopsy strategies and completed the study. INTERVENTION: The order of performing biopsies using visual registration and a computer-assisted MRI/ultrasound image-fusion system (SmartTarget) on each patient was randomised. The equipment was reset between biopsy strategies to mitigate incorporation bias. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The proportion of clinically significant prostate cancer (primary outcome: Gleason pattern ≥3+4=7, maximum cancer core length ≥4mm; secondary outcome: Gleason pattern ≥4+3=7, maximum cancer core length ≥6mm) detected by each method was compared using McNemar's test of paired proportions. RESULTS AND LIMITATIONS: The two strategies combined detected 93 clinically significant prostate cancers (72% of the cohort). Each strategy detected 80/93 (86%) of these cancers; each strategy identified 13 cases missed by the other. Three patients experienced adverse events related to biopsy (urinary retention, urinary tract infection, nausea, and vomiting). No difference in urinary symptoms, erectile function, or quality of life between baseline and follow-up (median 10.5 wk) was observed. The key limitations were lack of parallel-group randomisation and a limit on the number of targeted cores. CONCLUSIONS: Visual-registration and image-fusion targeting strategies combined had the highest detection rate for clinically significant cancers. Targeted prostate biopsy should be performed using both strategies together. PATIENT SUMMARY: We compared two prostate cancer biopsy strategies: visual registration and image fusion. A combination of the two strategies found the most clinically important cancers and should be used together whenever targeted biopsy is being performed.

Technological aspects of delivering cryotherapy for prostate cancer.

Since the era of prostate specific antigen (PSA) testing, there has been a stage and grade migration seen with prostate cancer along with a reduction in mortality. Subsequently, concerns have been raised about the over treatment of patients following the diagnosis of localized prostate cancers. Cryotherapy, in which extremely low temperatures induce cell death via multiple mechanisms, has seen a drastic improvement in its technology since the 1800s. Such advances have improved oncological outcomes while reducing complication rates. Furthermore, technological advances have allowed the development of focal cryotherapy which aims to reduce morbidity associated with more radical whole-gland therapies. There is growing evidence that focal cryotherapy provides good oncological and morbidity rates when compared with traditional radical/whole-gland therapies.

Synthesis and hypoglycemic activity of some new theophylline derivatives.

Thirty-one new theophylline derivatives have been synthesized and evaluated for their hypoglycemic activity. Compounds 24 (56% reduction) and 31 (57% reduction) showed better hypoglycemic activity than the standard drug glibenclamide which showed 52% reduction in serum glucose level. Compound 27 remarkably reduced serum glucose level by 53%. Ten compounds showed varying degrees of hypoglycemic activity ranging from 20 to 37% reduction in serum glucose level compared to the standard drug. The aromatic amide functionality is the common feature of these theophylline hypoglycemic derivatives. However, anthranilamide and or aliphatic amides proved to be the least active compounds in the present series.

Developing a robotic prostatectomy service and a robotic fellowship programme - defining the learning curve.

INTRODUCTION: Robotic radical prostatectomy (RRP) is an established treatment for prostate cancer in selected centres with appropriate expertise. We studied our single-centre experience of developing a RRP service and subsequent training of 2 additional surgeons by the initial surgeon and the introduction of United Kingdom's first nationally accredited robotic fellowship training programme. We assessed the learning curve of the 3 surgeons with regard to peri-operative outcomes and oncological results. PATIENTS AND METHODS: Three hundred consecutive patients underwent RRP between November 2008 and August 2012. Patients were divided into 3 equal groups (Group 1, case 1-100; Group 2, case 101-200; and Group 3, case 201-300). Age, ASA score, preoperative co-morbidities and indications for laparoscopic radical prostatectomy were comparable for all 3 patient groups. Peri-operative and oncological outcomes were compared across all 3 groups to assess the impact of the learning curve for laparoscopic radical prostatectomy. All surgical complications were classified using the Clavien-Dindo system. RESULTS: The mean age was 60.7 years (range 41-74). There was a significant reduction in the mean console time (p < 0.001), operating time (p < 0.001), mean length of hospital stay (p < 0.001) and duration of catheter (p < 0.001) between the 3 groups as the series progressed. The two most important factors predictive of positive surgical margins (PSM) at RRP were the initial prostate specific antigen (PSA) and tumor stage at diagnosis. The overall PSM rate was 26.7%. For T2/T3 tumors the incidence of PSM reduced as the series progressed (Group 1-22%, Group 2-32% and Group 3-26%). The incidence of major complications i.e. grade Clavien-Dindo system score ≤ III was 2% (6/300). CONCLUSION: RRP is a safe procedure with low morbidity. As surgeons progress through the learning curve peri-operative parameters and oncological outcomes improve. This learning curve is not affected by the introduction of a fellowship-training programme. Using a carefully structured mentored approach, RRP can be safely introduced as a new procedure without compromising patient outcomes.

Molecular properties prediction, synthesis and antimicrobial activity of some newer oxadiazole derivatives.

In present investigation a series of 28 oxadiazole analogues (AB1-AB28) were subjected to molecular properties prediction, drug-likeness by Molinspiration (Molinspiration, 2008) & MolSoft (MolSoft, 2007) softwares, lipophilicity and solubility parameters using ALOGPS 2.1 program. Out of 28 analogues only 16 were chosen on the basis of Lipinski "Rule of Five" (Ro5) for the synthesis and antimicrobial screening as oral bioavailable drugs/leads. Maximum drug-likeness model score (1.22) was found to be of compound AB13. Selected compounds (AB1-AB2), (AB5-AB9), (AB12-AB16), (AB18-AB21) were synthesized and characterized by IR, NMR and mass spectral analysis followed by antibacterial and antifungal screening. It was observed that compounds showed moderate to good antibacterial activity, but their antifungal activity was somewhat moderate. Compounds AB13 and AB20 showed pronounced activity against all bacterial and fungal strains. We had noticed that compounds (AB13, AB20) bearing OH group at one of the phenyl ring of oxadiazole exhibited good antimicrobial properties and their drug-likeness model score were also predicted maximum among the series.