Kinetics and mechanism of formation of nickel(II)porphyrin and its interaction with DNA in aqueous medium.

Kinetics between 5,10,15,20-tetrakis(N-methylpyridium-4-yl)porphyrin and Ni2+ species were investigated in aqueous solution at 25 ±1 °C in I = 0.10 M (NaNO3). Speciation of Ni2+ was done in I = 0.10 M (NaNO3) for knowing distribution of Ni2+ species with solution pH. Experimental data were compared with speciation diagram constructed from the values of hydrolysis constants of Ni2+ ion. Speciation data showed that hexaaquanickel(II) ions took place in hydrolysis reactions through formation of [Ni(OH2)6-n(OH)n]2-n species with solution pH. According to speciation of Ni2+ and pH dependent rate constants, rate expression can be written as: d[Ni(TMPyP)4+]/dt = (k 1[Ni2+ (aq)] + k 2[Ni(OH)+ (aq)] + k 3[Ni(OH)2 o (aq)] + k 4[Ni(OH)3 - (aq)])[H2TMPyP4+], where k 1, k 2, k 3 and k 4 were found to be k 1 = (0.62 ± 0.22) × 10-2; k 2 = (3.60 ± 0.40) × 10-2; k 3 = (2.09 ± 0.52) × 10-2, k 4 = (0.53 ± 0.04) × 10-2 M-1s-1 at 25 ±1 °C, respectively. Formation of hydrogen bonding between [Ni(H2O)5(OH)]+ and [H2TMPyP]4+ causes enhanced reactivity. Rate of formation of [Ni(II)TMPyP]4+ complex was to be 3.99 × 10-2 M-1s-1 in I = 0.10 M, NaNO3 (25 ± 1 °C). UV-Vis and fluorescence data suggested that [Ni(II)TMPyP]4+ and [H2(TMPyP)]4+ interact with DNA via outside binding with self-stacking and intercalation, respectively. SYNOPSIS. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12039-021-01945-y.

Upstaging and Survival Outcomes for Non-Muscle Invasive Bladder Cancer After Radical Cystectomy: Results from the International Robotic Cystectomy Consortium.

Introduction: We sought to describe the incidence, risk factors, and survival outcomes associated with pathologic upstaging from non-muscle invasive bladder cancer (NMIBC) to muscle invasive bladder cancer (MIBC) after robot-assisted radical cystectomy (RARC). Methods: We reviewed the International Robotic Cystectomy Consortium database between 2004 and 2020. Upstaging was defined as ≥pT2 or pathologic node positive (pN+) at final pathology analysis from clinical

A comparative propensity score-matched analysis of perioperative outcomes of intracorporeal vs extracorporeal urinary diversion after robot-assisted radical cystectomy: results from the International Robotic Cystectomy Consortium.

OBJECTIVE: To compare the perioperative outcomes of intracorporeal (ICUD) vs extracorporeal urinary diversion (ECUD) after robot-assisted radical cystectomy (RARC). PATIENTS AND METHODS: We retrospectively reviewed the prospectively maintained International Robotic Cystectomy Consortium (IRCC) database. A total of 972 patients from 28 institutions who underwent RARC were included. Propensity score matching was used to match patients based on age, gender, body mass index (BMI), American Society of Anesthesiologists Score (ASA) score, Charlson Comorbidity Index (CCI) score, prior radiation and abdominal surgery, receipt of neoadjuvant chemotherapy, and clinical staging. Matched cohorts were compared. Multivariate stepwise logistic and linear regression models were fit to evaluate variables associated with receiving ICUD, operating time, 90-day high-grade complications (Clavien-Dindo Classification Grade ≥III), and 90-day readmissions after RARC. RESULTS: Utilisation of ICUD increased from 0% in 2005 to 95% in 2018. The ICUD patients had more overall complications (66% vs 58%, P = 0.01) and readmissions (27% vs 17%, P = 0.01), but not high-grade complications (21% vs 24%, P = 0.22). A more recent RC era and ileal conduit diversion were associated with receiving an ICUD. Higher BMI, ASA score ≥3, and receiving a neobladder were associated with longer operating times. Shorter operating time was associated with male gender, older age, ICUD, and centres with a larger annual average RC volume. Longer intensive care unit stay was associated with 90-day high-grade complications. Higher CCI score, prior radiation therapy, neoadjuvant chemotherapy, and ICUD were associated with a higher risk of 90-day readmissions. CONCLUSIONS: Utilisation of ICUD has increased over the past decade. ICUD was associated with more overall complications and readmissions compared to ECUD, but not high-grade complications.

Early Oncologic Failure after Robot-Assisted Radical Cystectomy: Results from the International Robotic Cystectomy Consortium.

PURPOSE: We sought to investigate the prevalence and variables associated with early oncologic failure. MATERIALS AND METHODS: We retrospectively reviewed the IRCC (International Radical Cystectomy Consortium) database of patients who underwent robot-assisted radical cystectomy since 2003. The final cohort comprised a total of 1,894 patients from 23 institutions in 11 countries. Early oncologic failure was defined as any disease relapse within 3 months of robot-assisted radical cystectomy. All institutions were surveyed for the pneumoperitoneum pressure used, breach of oncologic surgical principles, and techniques of specimen and lymph node removal. A multivariate model was fit to evaluate predictors of early oncologic failure. The Kaplan-Meier method was applied to depict disease specific and overall survival, and Cox proportional regression analysis was used to evaluate predictors of disease specific and overall survival. RESULTS: A total of 305 patients (22%) experienced disease relapse, which was distant in 220 (16%), local recurrence in 154 (11%), peritoneal carcinomatosis in 17 (1%) and port site recurrence in 5 (0.4%). Early oncologic failure developed in 71 patients (5%) at a total of 10 institutions. The incidence of early oncologic failure decreased from 10% in 2006 to 6% in 2015. On multivariate analysis the presence of any complication (OR 2.87, 95% CI 1.38-5.96, p = 0.004), pT3 or greater disease (OR 3.73, 95% CI 2.00-6.97, p <0.001) and nodal involvement (OR 2.14, 95% CI 1.21-3.80, p = 0.008) was a significant predictor of early oncologic failure. Patients with early oncologic failure demonstrated worse disease specific and overall survival (23% and 13%, respectively) at 1 and 3 years compared to patients who experienced later or no recurrences (log rank p <0.001). CONCLUSIONS: The incidence of early oncologic failure following robot-assisted radical cystectomy has decreased with time. Disease related rather than technical related factors have a major role in early oncologic failure after robot-assisted radical cystectomy.

How to develop a simulation programme in urology.

What's known on the subject? and What does the study add? Inanimate trainers and simulators have been shown to facilitate the skill acquisition of urologists. However, there are significant challenges to integrating standalone simulation programmes into mainstream urology curricula. This study provides a framework to overcome these challenges and discusses the advantages of centralised urology simulation centres and their potential to serve as key adjuncts in the certification and validation process of urologists. Fixed performance-based outcomes of inanimate trainers and simulators have been praised as useful adjuncts in urology for reducing the learning curve associated with the acquisition of new technical and non-technical skills without compromising patient safety. Simulators are becoming an integral part of the urology training curriculum and their effectiveness is totally dependent on the structure of the programme implemented. The present paper discusses the fundamental concepts of centralized urology centres and their potential to serve as key adjuncts in the certification and validation process of urologists. In summary, proficiency-based curricula with well structured endpoints and objective tools for validating proficiency are critical in developing a simulation programme in urology. We concludes that more educational research into the outcomes of integrated urology curricula followed by trainee/trainer opinion surveys will help address some of these criteria.

What is the current status of revalidation in urology?

The aim of revalidation (or maintenance of certification) is to reassure patients, the general public, employers and other healthcare professionals that an individual is fit to practice. It may lead to a reduction in near misses or adverse events. The process of revalidation entails a commitment to the provision of lifelong learning and assessment of clinical practice that ultimately ensure patient safety. Lifelong learning addresses knowledge and skills, whereas assessment of clinical practice ensures quality of care. Various learning and assessment tools are available in clinical practice; however, the tools for revalidation are not validated at specialist level. Further research is needed to develop and implement evidence-based structured programmes of revalidation that consider the holistic needs of modern urologists.

Effectiveness of procedural simulation in urology: a systematic review.

PURPOSE: We analyzed studies validating the effectiveness and deficiencies of simulation for training and assessment in urology. We documented simulation types (synthetic, virtual reality and animal models), participant experience level and tasks performed. The feasibility, validity, cost-effectiveness, reliability and educational impact of the simulators were also evaluated. MATERIALS AND METHODS: The MEDLINE®, EMBASE™ and PsycINFO® databases were systematically searched until September 2010. References from retrieved articles were reviewed to broaden the search. RESULTS: The study included case reports, case series and empirical studies of training and assessment in urology using procedural simulation. The model name, training tasks, participant level, training duration and evaluation scoring were extracted from each study. We also extracted data on face, content and construct validity. Most studies suitably addressed content, construct and face validation as well as the feasibility, educational impact and cost-effectiveness of simulation models. Synthetic, animal and virtual reality models were demonstrated to be effective training and assessment tools for junior trainees. Few investigators looked at the transferability of skills from simulation to real patients. CONCLUSIONS: Current simulation models are valid and reliable for the initial phase of training and assessment. For advanced and specialist level skill acquisition animal models can be used but availability is limited due to supply shortages and ethical restrictions. More research is needed to validate simulated environments for senior trainees and specialists.

Repeat botulinum toxin-A injections for treatment of adult detrusor overactivity.

Intravesical injections of botulinum toxin-A have become established as an effective therapy in the management of neurogenic and idiopathic detrusor overactivity that is refractory to treatment with anticholinergic medication. The effects of the toxin are finite and repeated injections are required to sustain the beneficial therapeutic effects. The available data suggest a reproducible and sustained improvement in symptoms as well as urodynamic parameters following repeated injections of botulinum toxin-A. The reported incidence of adverse events is low and resistance to the toxin is uncommon. The timing of repeat injections within the published data is variable, reflecting differing practise among clinicians, but is typically 6-12 months. Larger scale studies are still required to clarify the usefulness of botulinum toxin-A as a long-term treatment in the management of detrusor overactivity.

Assessment and maintenance of competence in urology.

Urology is becoming increasingly reliant on inter-disciplinary collaboration. As a result of this interaction and developments in technology, the existing system of training, certification and recertification needs revision. The skill-set required of urologists has become multidimensional. As the field of urology continues to evolve, the recognition of the need for objective and efficient certification for trainees and a recertification program for specialists has increased. Training programs need to provide a curriculum focused on knowledge, communication, cognitive and technical skills, with the inclusion of simulation-based training. For specialists, the benefits of teaching through mentorship should be evaluated, and outcome-based assessment of patient morbidity and mortality needs to be further developed and validated.

Urethral diverticular carcinoma: an overview of current trends in diagnosis and management.

AIMS: To review the management of female urethral diverticular tumours, and rationalize treatment protocols. METHODS: A literature search through Medline, Psychoinfo, EMBASE and the Cochrane library from 1951 was performed for all reports and series of urethral diverticular tumours. RESULTS: A total of one male patient and 75 female patients were reported, with data on demographics, presentation, diagnosis, treatment modalities, recurrence rates and mortality. There is considerable variation in the method of reporting outcomes, and heterogeneity in treatment methods. CONCLUSION: There appears to be no current consensus in the management of these rare tumours. There is an urgent need to establish an international registry of rare tumours to help formulate guidelines on management of such tumours. We propose a management algorithm based on the evidence gathered from review of the published literature.

A pilot study to assess the feasibility, safety and cost of robotic assisted total hysterectomy and bilateral salpingo-oophorectomy.

The aim of this study was to evaluate the safety, feasibility and cost-effectiveness of robotic assisted total hysterectomy and bilateral salpingo-oophorectomy (RATHBSO). Sixteen women underwent this new procedure for a variety of gynaecological indications. Outcome measures included operating time, estimated blood loss, length of hospital stay and cost. No intra-operative complications were recorded. Fifteen patients were discharged on day 1 following the procedure, and one patient stayed an extra day for pain relief. The cost of the procedure compared favourably with other surgical hysterectomy techniques. We conclude that RATHBSO is a feasible and safe surgical technique with all the advantages of minimal access surgery and equivalent cost.

Repeated injections of botulinum toxin-A for idiopathic detrusor overactivity.

OBJECTIVES: To report the efficacy and safety of repeated injections of botulinum toxin-A (BTX-A) in treating idiopathic detrusor overactivity refractory to anticholinergics. Furthermore, we describe whether dose alteration in patients with poor responses or voiding dysfunction after initial treatment can improve outcomes. METHODS: A cohort of 34 patients who participated in a clinical trial was followed up and their progress reported. Twenty from this group had >1 BTX-A injection. Each patient received 200 U BTX-A initially, with subsequent injections between 100 and 300 U, administered by a trigone-sparing flexible cystoscopic technique. Efficacy was measured using voiding diaries and quality of life (QoL) assessed with Incontinence Impact Questionnaire-7 and Urogenital Distress Inventory-6 questionnaires. Urodynamic data were obtained for injections 1-3. All measurements were performed before and 3 months after injections. RESULTS: Twenty patients received a repeat injection and of these 9 subsequently received a third and fourth injection. Significant improvements in overactive bladder syndrome symptoms and QoL were observed after each injection as compared with baseline. Maximum cystometric capacity and bladder compliance increased with decrease in the maximum detrusor pressure during filling cystometry. When comparing overactive bladder symptoms, QoL, and urodynamic parameters 3 months after the first and last injections, no significant differences were found. Nine patients had their BTX-A dose altered, with better outcomes in 5. The commonest reported problems were difficulty in emptying the bladder and urinary tract infection. CONCLUSIONS: BTX-A appears to be effective and safe after repeated administration in patients with idiopathic detrusor overactivity. Certain patients will benefit from dose optimization to improve efficacy or prevent voiding dysfunction.

Current status of robotic assisted pelvic surgery and future developments.

AIMS: The aim of this review is to assess the role of robotics in pelvic surgery in terms of outcomes. We have also highlighted the issues related to training and future development of robotic systems. MATERIALS AND METHODS: We searched MEDLINE, EMBASE and the Cochrane Databases from 1980 to 2009 for systematic reviews of randomised controlled trials, prospective observational studies, retrospective studies and case reports assessing robotic surgery. RESULTS: During the last decade, there has been a tremendous rise in the use of robotic surgical systems for all forms of precision operations including pelvic surgery. The short-term results of robotic pelvic surgery in the fields of urology, colorectal surgery and gynaecology have been shown to be comparable to the laparoscopic and open surgery. Robotic surgery offers an opportunity where many of these obstacles encountered during open and laparoscopic surgery can be overcome. CONCLUSIONS: Robotic surgery is a continually advancing technology, which has opened new horizons for performing pelvic surgery with precision and accuracy. Although its use is rapidly expanding in all surgical disciplines, particularly in pelvic surgery, further comparative studies are needed to provide robust guidance about the most appropriate application of this technology within the surgical armamentarium.

Robotic-assisted radical cystectomy.

OBJECTIVE: To evaluate the emerging role of robotic-assisted radical cystectomy (RARC) in the management of bladder cancer. METHODS: Review of the published literature on robotic-assisted radical cystectomy, including data from our cystectomy series of 30 patients. RESULTS: Nearly 150 procedures have been performed worldwide. The benefits of robotic-assisted operations are similar to those of laparoscopically-performed procedures. RARC appears to be technically safe, oncologically and functionally equivalent to open (ORC) and laparoscopic radical cystectomy (LRC). However, RARC offers superior ergonomics and better vision. These benefits come at extra initial capital expenditure and subsequent higher maintenance costs. CONCLUSION: With the rapid spread of robotics, it is likely that RARC will become the standard of care in units with access to the technology.

Robotic-assisted laparoscopic radical cystectomy with extracorporeal urinary diversion: initial experience.

BACKGROUND: The use of robotic technology for laparoscopic prostatectomy is now well established. The same cannot yet be said of robotic-assisted laparoscopic radical cystectomy (RARC), which is performed in just a few centres worldwide. OBJECTIVE: We present our technique and experience of this procedure using the da Vinci surgical system. DESIGN, SETTING, AND PARTICIPANTS: From 2004 to 2007, 23 patients underwent RARC and urinary diversion at our institution. SURGICAL PROCEDURE: We report the development of our technique for RARC, which involves posterior dissection, lateral pedicle control, anterior dissection, and lymphadenectomy prior to either ileal conduit urinary diversion or Studer pouch reconstruction performed extracorporeally. MEASUREMENTS: Demographic and perioperative data were recorded prospectively. Oncologic and functional outcomes were assessed at 3- to 6-mo intervals. RESULTS AND LIMITATIONS: To date, 23 patients have undergone this procedure at our institution. Of those, 19 had ileal loop urinary diversion and 4 were suitable for Studer pouch reconstruction. Mean total operative time plus or minus (+/-) standard deviation (SD) was 397+/-83.8min. Mean blood loss +/-SD was 278+/-229ml with one patient requiring a blood transfusion. Surgical margins were clear in all patients with a median +/-SD of 16+/-8.9 lymph nodes retrieved. The complication rate was 26%. At a mean follow-up +/-SD of 17+/-13 (range 4-40) mo, one patient had died of metastatic disease and one other is alive with metastases. The remaining 21 patients are alive without recurrence. CONCLUSIONS: RARC remains a procedure in evolution in the small number of centres carrying out this type of surgery. Our initial experience confirms that it is feasible with acceptable morbidity and good short-term oncologic results.

Living-unrelated donor renal transplantation: an alternative to living-related donor transplantation?

INTRODUCTION: An increasing number of living-unrelated, kidney donor transplants are being performed in our unit. We present a comparison of living-unrelated (LURD) and living-related donor (LRD) renal transplant outcomes and analyse influencing factors. PATIENTS AND METHODS: We retrospectively analysed the outcome of all living-donor renal transplants performed at our centre from 1993 to 2004. The parameters studied included patient and graft survival, functioning status of grafts (determined by estimated GFR) at last follow-up and any rejection episodes. Multivariate analysis was performed for recipient and donor age, ethnicity, HLA matching and re-transplants. RESULTS: A total of 322 live donor kidney transplants (LRD, n = 261; LURD, n = 61) were carried out over this period. Mean recipient age was 28 +/- 16 years in the LRD group and 48 +/- 12 years in LURD, while mean age of the donors was 43 +/- 11 years and 48 +/- 10 years, respectively. Caucasians constituted 80% of all the living donors. Amongst LRD, parents were the commonest (58%) donors followed by siblings (35%). In LURD, 80% were spouses. A total of 33 grafts failed, 30 in LRD (11%) and 3 in LURD (5%). Thirteen patients died, 11 (4.2%) in LRD (7 with functioning graft) and 2 (3.3%) in LURD (1 with functioning graft). Acute rejections occurred in 41% recipients in LRD and 35% in LURD (P = 0.37). Estimated GFR was lower in LURD than in LRD (49 +/- 14 versus 59 +/- 29 ml/min/1.73 m(2); P = 0.032). One- and 3-year patient survival for LRD and LURD was 98.7% and 96.3% and 97.7% and 95%, respectively (P = 0.75). One- and 3-year graft survival was equivalent at 94.8% and 92.3% for LRD, and 98.4% and 93.7% for LURD, respectively (P = 0.18). CONCLUSIONS: Outcome of LRD and LURD is comparable in terms of patient and graft survival, acute rejection rate and estimated GFR despite differences in demographics, HLA matching and re-transplants of recipients.

Management of cystinuric patients: an observational, retrospective, single-centre analysis.

OBJECTIVE: A critical appraisal of the management of patients with cystine stones treated in our unit in the past 6 years and to analyze the outcome of multimodality therapies. STUDY DESIGN: An observational, single-centre retrospective study. METHODS: We reviewed the records of all patients with stones referred to our centre over a 6-year period from 1998 to 2005. Data recorded included demographic details, medical therapies received/prescribed, compliance with medical therapies, mode of treatment, stone clearance and any recurrence during this period of study. RESULTS: A total of 30 cystinuric patients were treated in our institution over the period of 6 years from 1998 to early 2005. Of these 16 were males and 14 females with an average age at last follow-up of 39 years (range 15-70). Two patients were successfully managed medically. The remaining patients (n = 28) underwent a total of 237 procedures (pre- and postreferral to our unit), with an average of 7.9 procedures per patient for 126 stone episodes (4.2 episodes/patient). The modes of treatment included extracorporeal shockwave lithotripsy (n = 143), ureterorenoscopy and intracorporeal lithotripsy (n = 50), percutaneous nephrolithotomy (n = 28) and open procedures (n = 16). Two patients needed open surgery at our unit. Prior to referral to our dedicated unit, patients had received treatment with extracorporeal shockwave lithotripsy (multiple sessions), ureteroscopy (n = 14), percutaneous nephrolithotomy (n = 4) and open stone removal (n = 14). Most of the stones at our unit were managed using minimally invasive therapies. CONCLUSION: Compliance of cystinuric patients with medical treatment is often poor and patients experience recurrent stone episodes requiring multiple interventions. Modern management of cystine calculi should be with staged minimally invasive procedures to avoid the complications of multiple open procedures wherever possible along with appropriate medical prophylaxis.