Management of Lymph Node-positive Penile Cancer: A Systematic Review.

CONTEXT: Lymph node (LN) involvement in penile cancer is associated with poor survival. Early diagnosis and management significantly impact survival, with multimodal treatment approaches often considered in advanced disease. OBJECTIVE: To assess the clinical effectiveness of treatment options available for the management of inguinal and pelvic lymphadenopathy in men with penile cancer. EVIDENCE ACQUISITION: EMBASE, MEDLINE, the Cochrane Database of Systematic Reviews, and other databases were searched from 1990 to July 2022. Randomised controlled trials (RCTs), nonrandomised comparative studies (NRCSs), and case series (CSs) were included. EVIDENCE SYNTHESIS: We identified 107 studies, involving 9582 patients from two RCTs, 28 NRCSs, and 77 CSs. The quality of evidence is considered poor. Surgery is the mainstay of LN disease management, with early inguinal LN dissection (ILND) associated with better outcomes. Videoendoscopic ILND may offer comparable survival outcomes to open ILND with lower wound-related morbidity. Ipsilateral pelvic LN dissection (PLND) in N2-3 cases improves overall survival in comparison to no pelvic surgery. Neoadjuvant chemotherapy in N2-3 disease showed a pathological complete response rate of 13% and an objective response rate of 51%. Adjuvant radiotherapy may benefit pN2-3 but not pN1 disease. Adjuvant chemoradiotherapy may provide a small survival benefit in N3 disease. Adjuvant radiotherapy and chemotherapy improve outcomes after PLND for pelvic LN metastases. CONCLUSIONS: Early LND improves survival in nodal disease in penile cancer. Multimodal treatments may provide additional benefit in pN2-3 cases; however, data are limited. Therefore, individualised management of patients with nodal disease should be discussed in a multidisciplinary team setting. PATIENT SUMMARY: Spread of penile cancer to the lymph nodes is best managed with surgery, which improves survival and has curative potential. Supplementary treatment, including the use of chemotherapy and/or radiotherapy, may further improve survival in advanced disease. Patients with penile cancer with lymph node involvement should be treated by a multidisciplinary team.

Systematic Review and Meta-analysis of Minimally Invasive Procedures for Surgical Inguinal Nodal Staging in Penile Carcinoma.

CONTEXT: There are several procedures for surgical nodal staging in clinically node-negative (cN0) penile carcinoma. OBJECTIVE: To evaluate the diagnostic accuracy, perioperative outcomes, and complications of minimally invasive surgical procedures for nodal staging in penile carcinoma. EVIDENCE ACQUISITION: A systematic review of the Medline, Embase, and Cochrane controlled trials databases and ClinicalTrials.gov was conducted. Published and ongoing studies reporting on the management of cN0 penile cancer were included without any design restriction. Outcomes included the false negative (FN) rate, the number of nodes removed, surgical time, and postoperative complications. EVIDENCE SYNTHESIS: Forty-one studies were eligible for inclusion. Four studies comparing robot-assisted (RA-VEIL) and video-endoscopic inguinal lymphadenectomy (VEIL) to open inguinal lymph node dissection (ILND) were suitable for meta-analysis. A descriptive synthesis was performed for single-arm studies on modified open ILND, dynamic sentinel node biopsy (DSNB) with and without preoperative inguinal ultrasound (US), and fine-needle aspiration cytology (FNAC). DSNB with US + FNAC had lower FN rates (3.5-22% vs 0-42.9%) and complication rates (Clavien Dindo grade I-II: 1.1-20% vs 2.9-11.9%; grade III-V: 0-6.8% vs 0-9.4%) in comparison to DSNB alone. Favourable results were observed for VEIL/RA-VEIL over open ILND in terms of major complications (2-10.6% vs 6.9-40.6%; odds ratio [OR] 0.18; p < 0.01). Overall, VEIL/RA-VEIL had lower wound-related complication rates (OR 0.14; p < 0.01), including wound infections (OR 0.229; p < 0.01) and skin necrosis (OR 0.16; p < 0.01). The incidence of lymphatic complications varied between 20.6% and 49%. CONCLUSIONS: Of all the surgical staging options, DSNB with inguinal US + FNAC had the lowest complication rates and high diagnostic accuracy, especially when performed in high-volume centres. If DSNB is not available, favourable results were also found for VEIL/RA-VEIL over open ILND. Lymphatic-related complications were comparable across open and video-endoscopic ILND. PATIENT SUMMARY: We reviewed studies on different surgical approaches for assessing lymph node involvement in cases with penile cancer. The results show that a technique called dynamic sentinel node biopsy with ultrasound guidance and fine-needle sampling has high diagnostic accuracy and low complication rates. For lymph node dissection in penile cancer cases, a minimally invasive approach may offer favourable postoperative outcomes.

European Association of Urology-American Society of Clinical Oncology Collaborative Guideline on Penile Cancer: 2023 Update.

CONTEXT: Penile cancer is a rare disease but has a significant impact on quality of life. Its incidence is increasing, so it is important to include new and relevant evidence in clinical practice guidelines. OBJECTIVE: To provide a collaborative guideline that offers worldwide physician and patient guidance for the management of penile cancer. EVIDENCE ACQUISITION: Comprehensive literature searches were performed for each section topic. In addition, three systematic reviews were conducted. Levels of evidence were assessed, and a strength rating for each recommendation was assigned according to the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) methodology. EVIDENCE SYNTHESIS: Penile cancer is a rare disease but its global incidence is increasing. Human papillomavirus (HPV) is the main risk factor for penile cancer and pathology should include an assessment of HPV status. The main aim of primary tumour treatment is complete tumour eradication, which has to be balanced against optimal organ preservation without compromising oncological control. Early detection and treatment of lymph node (LN) metastasis is the main determinant of survival. Surgical LN staging with sentinel node biopsy is recommended for patients with a high-risk (≥pT1b) tumour with cN0 status. While (inguinal) LN dissection remains the standard for node-positive disease, multimodal treatment is needed in patients with advanced disease. Owing to a lack of controlled trials and large series, the levels of evidence and grades of recommendation are low in comparison to those for more common diseases. CONCLUSIONS: This collaborative penile cancer guideline provides updated information on the diagnosis and treatment of penile cancer for use in clinical practice. Organ-preserving surgery should be offered for treatment of the primary tumour when feasible. Adequate and timely LN management remains a challenge, especially in advanced disease stages. Referral to centres of expertise is recommended. PATIENT SUMMARY: Penile cancer is a rare disease that significantly impacts quality of life. While the disease can be cured in most cases without lymph node involvement, management of advanced disease remains challenging. Many unmet needs and unanswered questions remain, underlining the importance of research collaborations and centralisation of penile cancer services.

What Is the Most Effective Management of the Primary Tumor in Men with Invasive Penile Cancer: A Systematic Review of the Available Treatment Options and Their Outcomes.

Context: The primary lesion in penile cancer is managed by surgery or radiation. Surgical options include penile-sparing surgery, amputative surgery, laser excision, and Moh's micrographic surgery. Radiation is applied as external beam radiotherapy (EBRT) and brachytherapy. The treatment aims to completely remove the primary lesion and preserve a sufficient functional penile stump. Objective: To assess whether the 5-yr recurrence-free rate and other outcomes, such as sexual function, quality of life, urination, and penile preserving length, vary between various treatment options. Evidence acquisition: The EMBASE, MEDLINE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (CENTRAL; Cochrane HTA, DARE, HEED), Google Scholar, and ClinicalTrials.gov were searched for publications from 1990 through May 2021. Randomized controlled trials, nonrandomized comparative studies (NRCSs), and case series (CSs) were included. Evidence synthesis: The systematic review included 88 studies, involving 9578 men from 16 NRCSs and 72 CSs. The cumulative mean 5-yr recurrence-free rates were 82.0% for penile-sparing surgery, 83.9% for amputative surgery, 78.6% for brachytherapy, 55.2% for EBRT, 69.4% for lasers, and 88.2% for Moh's micrographic surgery, as reported from CSs, and 76.7% for penile-sparing surgery and 93.3% for amputative surgery, as reported from NRCSs. Penile surgery affects sexual function, but amputative surgery causes more appearance concerns. After brachytherapy, 25% of patients reported sexual dysfunction. Both penile-sparing surgery and amputative surgery affect all aspects of psychosocial well-being. Conclusions: Despite the poor quality of evidence, data suggest that penile-sparing surgery is not inferior to amputative surgery in terms of recurrence rates in selected patients. Based on the available information, however, broadly applicable recommendations cannot be made; appropriate patient selection accounts for the relative success of all the available methods. Patient summary: We reviewed the evidence of various techniques to treat penile tumor and assessed their effectiveness in oncologic control and their functional outcomes. Penile-sparing as well as amputative surgery is an effective treatment option, but amputative surgery has a negative impact on sexual function. Penile-sparing surgery and radiotherapy are associated with a higher risk of local recurrence, but preserve sexual function and quality of life better. Laser and Moh's micrographic surgery could be used for smaller lesions.

The obliterated ureteric orifice: a nightmare for the pelvic surgeon or a routine-job for the endo-urologist? Case report of a standardized endoscopic approach.

We present the endoscopic management of two cases of complete ureteric occlusion at vesico-ureteral junction (VUJ) level following iatrogenic injury. Case 1 is a 60-year-old man who developed bilateral ureteric injury at the level of the VUJ following robot-assisted radical prostatectomy (RARP) for Gleason 3 + 4 = 7 T2bN0 prostate cancer. Case 2 is an 81-year-old man with history of recurrent G2pTa transitional cell carcinoma of the bladder originally diagnosed in 2005 and history of radical radiotherapy for prostate cancer. At his most recent transurethral resection of bladder tumour, the left ureteric orifice was not visualized. We describe step-by-step our technique in restoring continuity of the ureter with minimally invasive endoscopic approach, resulting in excellent long-term upper tract drainage for our patients. To our knowledge, combined utilization of a Collins knife to incise the area around the ureteric orifice to unearth them is not reported. We aim to report our technique and its outcomes.

A systematic review of methodological principles and delivery of surgical simulation bootcamps.

BACKGROUND: The growth of "bootcamp style" simulation training in surgical practice has been exponential over the last decade. Developing and delivering a surgical bootcamp requires a significant investment. This systematic review aims to identify the key components that allow for a successful and rewarding surgical bootcamp course to be implemented that can be applied to all surgical specialities. METHODS: To understand the surgical bootcamp principles and delivery mechanisms, we searched peer-reviewed, English language studies published between 2000 and 21. RESULTS: From 137 articles, 14 studies with a Medical Education Research Quality Instrument Score of >11.5 were included. Most studies followed the core components; delivery at transition (12), mapping syllabus (13), multimodality delivery (14), and deliberate practice with formative feedback (12) apart from 1:1 training by only 2 studies. CONCLUSIONS: Our review suggests that Surgical bootcamp can be an extremely useful education tool for trainees if 5 pillars of a boot camp are respected.

A Systematic Review of the Impact of Surgeon and Hospital Caseload Volume on Oncological and Nononcological Outcomes After Radical Prostatectomy for Nonmetastatic Prostate Cancer.

CONTEXT: The impact of surgeon and hospital volume on outcomes after radical prostatectomy (RP) for localised prostate cancer (PCa) remains unknown. OBJECTIVE: To perform a systematic review on the association between surgeon or hospital volume and oncological and nononcological outcomes following RP for PCa. EVIDENCE ACQUISITION: Medline, Medline In-Process, Embase, and the Cochrane Central Register of Controlled Trials were searched. All comparative studies for nonmetastatic PCa patients treated with RP published between January 1990 and May 2020 were included. For inclusion, studies had to compare hospital or surgeon volume, defined as caseload per unit time. Main outcomes included oncological (including prostate-specific antigen persistence, positive surgical margin [PSM], biochemical recurrence, local and distant recurrence, and cancer-specific and overall survival) and nononcological (perioperative complications including need for blood transfusion, conversion to open procedure and within 90-d death, and continence and erectile function) outcomes. Risk of bias (RoB) and confounding assessments were undertaken. Both a narrative and a quantitative synthesis were planned if the data allowed. EVIDENCE SYNTHESIS: Sixty retrospective comparative studies were included. Generally, increasing surgeon and hospital volumes were associated with lower rates of mortality, PSM, adjuvant or salvage therapies, and perioperative complications. Combining group size cut-offs as used in the included studies, the median threshold for hospital volume at which outcomes start to diverge is 86 (interquartile range [IQR] 35-100) cases per year. In addition, above this threshold, the higher the caseload, the better the outcomes, especially for PSM. RoB and confounding were high for most domains. CONCLUSIONS: Higher surgeon and hospital volumes for RP are associated with lower rates of PSMs, adjuvant or salvage therapies, and perioperative complications. This association becomes apparent from a caseload of >86 (IQR 35-100) per year and may further improve hereafter. Both high- and low-volume centres should measure their outcomes, make them publicly available, and improve their quality of care if needed. PATIENT SUMMARY: We reviewed the literature to determine whether the number of prostate cancer operations (radical prostatectomy) performed in a hospital affects the outcomes of surgery. We found that, overall, hospitals with a higher number of operations per year have better outcomes in terms of cancer recurrence and complications during or after hospitalisation. However, it must be noted that surgeons working in hospitals with lower annual operations can still achieve similar or even better outcomes. Therefore, making hospital's outcome data publicly available should be promoted internationally, so that patients can make an informed decision where they want to be treated.

Endoscopic surgical simulation using low-fidelity and virtual reality transurethral resection simulators in urology simulation boot camp course: trainees feedback assessment study.

OBJECTIVES: The objective of our study was to study trainees' feedback and rating of models for training transurethral resection of bladder lesions (TURBT) and prostate (TURP) during simulation. METHODS: The study was performed during the ''Transurethral resection (TUR) module" at the boot camp held in 2019. Prior to the course, all trainees were required to evaluate their experience in performing TURBT and TURP procedures. Trainees simulated resection on two different models; low-fidelity tissue model (Samed, GmBH, Dresden, Germany) and virtual reality simulator (TURPMentor, 3D Systems, Littleton, US). Following the completion of the module, trainees completed a questionnaire using a 5-point Likert scale to evaluate their assessment of the models for surgical training. RESULTS: In total, 174 simulation assessments were performed by 56 trainees (Samed Bladder-40, Prostate-45, TURPMentor Bladder-51, Prostate-37). All trainees reported that they had performed < 50 TUR procedures. The Samed model median scores were for appearance (4/5), texture (5/5), feel (5/5) and conductibility (5/5). The TURPMentor median score was for appearance (4/5), texture and feel (4/5) and conductibility (4/5). The most common criticism of the Samed model was that it failed to mimic bleeding. In contrast, trainees felt that the TURPMentor haptic feedback was inadequate to allow for close resection and did not calibrate movements accurately. CONCLUSIONS: Our results demonstrate that both forms of simulators (low-fidelity and virtual reality) were rated highly by urology trainees and improve their confidence in performing transurethral resection and in fact complement each other in providing lower tract endoscopic resection simulation.

Global Assessment of Urological Endoscopic Skills (GAUES): development and validation of a novel assessment tool to evaluate endourological skills.

OBJECTIVE: To develop and evaluate an assessment tool for endourological skills during simulation including cystoscopy, ureteroscopy (URS) and transurethral resection (TUR) procedures. METHODS: We designed a Global Assessment of Urological Endoscopic Skills (GAUES) tool, comprised of nine endourology task-specific and two global-rating skills items. The tool was developed through two rounds of the Delphi process. The GAUES tool was used to assess acquisition of URS and TUR skills of novices (Year 2 core surgical trainees, CT2) and intermediate level trainees (residents at the start of the UK higher surgical training programme in Urology, Speciality Trainee Year 3, ST3) at the Urology Simulation Boot Camp (USBC) between 2016 and 2018. Validity was evaluated by comparing scores between trainees with different levels of urological experience. Inter-rater reliability was also assessed. RESULTS: We evaluated 130 residents, 52% of trainees were at an intermediate stage of training and 39% were novices. In all, 9% of the anonymous forms were missing demographics. The completion rate of the GAUES tool during the USBC for URS and TUR was 85% and 89%, respectively. Our analysis demonstrated a significant difference in all domains between intermediates and novices at assessment in URS, except for one domain more suited to clinical assessment (P = 0.226). There was excellent intraclass correlation (ICC) overall between the two experts' judgements, ICC = 0.841 (95% confidence interval 0.767-0.893; P < 0.001, n = 88). CONCLUSIONS: We have developed the novel GAUES tool for cystoscopic, URS and TUR skills. Overall, we demonstrated good face, content and construct validity and excellent reliability, suggesting that the GAUES tool can be useful for endourological skills assessment.

A Low-Cost Synthetic Abdominal Wall Model ("Raj Model") for the Training of Laparoscopic Port Insertion.

OBJECTIVE: To assess the content validity of a low-cost bench-top model ("Raj Model") for the training of laparoscopic port insertion at the Urology Simulation Bootcamp course (USBC). MATERIALS AND METHODS: A low-cost abdominal wall model of 40 × 40 cm was created to simulate laparoscopic port placement. The model was made using different synthetic materials to represent layers (skin-vinyl sheet, subcutaneous fat-10 mm soft foam, anterior rectus sheath and muscle-floor mat, posterior rectus sheath-masking wall tape, peritoneum-sellotape). Each model was used by up to 3 trainees to practise laparoscopic port placement. The model was assessed for content validity by trainees and experts using a 5-point Likert scale. RESULT: In total, 88 trainees and 6 experts participated in the study. For all aspects of the synthetic abdominal wall, good (4) or very good (5) scores ranged from 52.7-69.2%, whereas very poor (1) rating ranged from 0 to 4.3%. There was no significant difference in responses for the content validity of the model between trainees and experts. There was a high intraclass correlation amongst responses from trainees (0.89) and experts (0.79). Approximately 76.3% of trainees and experts felt that the model is suitable for training. CONCLUSION: This is the first validation study of a low-cost abdominal wall model for teaching laparoscopic port placement for trainees. Our study demonstrates that this synthetic model has high content validity and is useful for surgical training.

Colo-Pro: a pilot randomised controlled trial to compare standard bolus-dosed cefuroxime prophylaxis to bolus-continuous infusion-dosed cefuroxime prophylaxis for the prevention of infections after colorectal surgery.

Standard bolus-dosed antibiotic prophylaxis may not inhibit growth of antibiotic resistant colonic bacteria, a cause of SSIs after colorectal surgery. An alternative strategy is continuous administration of antibiotic throughout surgery, maintaining concentrations of antibiotics that inhibit growth of resistant bacteria. This study is a pilot comparing bolus-continuous infusion with bolus-dosed cefuroxime prophylaxis in colorectal surgery. This is a pilot randomised controlled trial in which participants received cefuroxime bolus-infusion (intervention arm) targeting free serum cefuroxime concentrations of 64 mg/L, or 1.5 g cefuroxime as a bolus dose four-hourly (standard arm). Patients in both arms received metronidazole (500 mg intravenously). Eligible participants were adults undergoing colorectal surgery expected to last for over 2 h. Results were analysed on an intention-to-treat basis. The study was successfully piloted, with 46% (90/196) of eligible patients recruited and 89% (80/90) of participants completing all components of the protocol. A trialled bolus-continuous dosing regimen was successful in maintaining free serum cefuroxime concentrations of 64 mg/L. No serious adverse reactions were identified. Rates of SSIs (superficial and deep SSIs) were lower in the intervention arm than the standard treatment arm (24% (10/42) vs. 30% (13/43)), as were infection within 30 days of operation (41% (17/43) vs 51% (22/43)) and urinary tract infections (2% (1/42) vs. 9% (4/43)). These infection rates can be used to power future clinical trials. This study demonstrates the feasibility of cefuroxime bolus-continuous infusion of antibiotic prophylaxis trials, and provides safety data for infusions targeting free serum cefuroxime concentrations of 64 mg/L. Trial registration: NCT02445859 .

Impact of urology simulation boot camp in improving endoscopic instrument knowledge.

Objective: Education and training of surgeons has traditionally focused on the development of individual knowledge, technical skills and decision making. Knowledge about endoscopic instruments is one of the core elements of urological training. We assessed the precourse knowledge of newly appointed urology trainees and the impact of boot camp in improving their knowledge. Methods: Newly appointed specialty trainees in urology took part in a pilot 5-day urology simulation boot camp (USBC). The aim of the USBC was to improve their confidence, procedural performance and non-technical skills, with one of the modules looking at the trainees' knowledge about common endoscopic instruments in urology. Delegates were first asked to identify and assemble the instruments, followed by one-to-one teaching about the instruments. An Objective Structured Assessment Tool was used to assess their knowledge in the identification and assembly of the cystoscope, resectoscope and optical urethrotome, before and at the end of the course. Results: Data of two successive boot camps were collected to assess knowledge of instruments of newly appointed urology trainees. Majority of the trainees had good precourse knowledge of the cystoscopy kit, with 84% able to correctly identify the parts. Seventy-six per cent of candidates were able to identify the resectoscope equipment, but only approximately a third of trainees were able to correctly identify the urethrotome kit. The assembly of cystoscope, resectoscope and urethrotome was performed correctly in 74%, 42% and 32% at baseline and 94%, 90% and 77% postcourse, respectively. Overall performance improved significantly in the postcourse assessment (<0.001). Conclusion: This urology boot camp has addressed gaps in trainees' core equipment knowledge and guided them to improve their knowledge with respect to identification and assembly of cystoscope, resectoscope and urethrotome.

'No visible lesions?'-an unusual case of Intestinal metaplasia of the bladder.

Intestinal metaplasia (IM) of the bladder is an extremely rare benign condition. The clinical features are similar to other bladder tumours. Its pathogenesis is unclear and its role as a precursor of adenocarcinoma has long been debated. Transurethral resection is the main form of treatment for IM. We report the case of a 49-year-old gentleman who presented with visible haematuria. He was submitted to multiple cystoscopies which showed no macroscopic irregularities. Radiological (CT urogram and multiparametric MRI) imaging revealed abnormalities within the bladder neck, suspicious of a neoplastic lesion. Following transurethral resection of his trigonal area, pathology demonstrated IM occurring on a background of cystitis glandularis. This case highlights the unusual difficulty in macroscopically diagnosing IM of the bladder compared to other neoplasms of the bladder. Therefore, in patients with persistent visible haematuria there should be a low threshold to perform biopsies.

An Evaluation of the Role of Simulation Training for Teaching Surgical Skills in Sub-Saharan Africa.

BACKGROUND: An estimated 5 billion people worldwide lack access to any surgical care, whilst surgical conditions account for 11-30% of the global burden of disease. Maximizing the effectiveness of surgical training is imperative to improve access to safe and essential surgical care on a global scale. Innovative methods of surgical training have been used in sub-Saharan Africa to attempt to improve the efficiency of training healthcare workers in surgery. Simulation training may have an important role in up-scaling and improving the efficiency of surgical training and has been widely used in SSA. Though not intended to be a systematic review, the role of simulation for teaching surgical skills in Sub-Saharan Africa was reviewed to assess the evidence for use and outcomes. METHODS: A systematic search strategy was used to retrieve relevant studies from electronic databases PubMed, Ovid, Medline for pertinent articles published until August 2016. Studies that reported the use of simulation-based training for surgery in Africa were included. RESULTS: In all, 19 articles were included. A variety of innovative surgical training methods using simulation techniques were identified. Few studies reported any outcome data. Compared to the volume of surgical training initiatives that are known to take place in SSA, there is very limited good quality published evidence for the use of simulation training in this context. CONCLUSIONS: Simulation training presents an excellent modality to enhance and improve both volume and access to high quality surgical skills training, alongside other learning domains. There is a desperate need to meticulously evaluate the appropriateness and effectiveness of simulation training in SSA, where simulation training could have a large potential beneficial impact. Training programs should attempt to assess and report learner outcomes.

The Validation of the Clinical Male Pelvic Trainer Mk 2-Advanced Models for Scrotal Examination Simulation.

OBJECTIVES: To validate the use of a novel physical model, the "Clinical Male Pelvic Trainer (CMPT) Mk 2-Advanced," for scrotal examination simulation and evaluate its use for surgical education. MATERIALS AND METHODS: A total of 7 CMPT Mk 2-Advanced scrotal models were used for teaching: normal, varicocele, testicular tumor, epididymal cyst, hydrocele, epididymo-orchitis, and indirect inguinoscrotal hernia. At 4 surgical courses in the West Yorkshire Foundation Deanery, UK, between 2015 and 2016, trainees were asked to assess their clinical experience, confidence levels in diagnosing scrotal pathology and simulation properties of the scrotal models on a 5-point Likert Scale. Expert responses were used to validate these findings. RESULTS: In total, 65 trainees and 12 experts (including 3 senior residents) participated in the study (n = 77). There was a positive-tailed distribution in responses from experts for realistic simulation of scrotal contents and pathology; only 1.5% and 14.4% of all responses by experts were scored as a "1" (strongly disagree) or "2" (disagree). The intraclass coefficient (κ) was 0.86 among experts. No significant differences between experts and trainees in assessment of simulation were observed. Following use of the models, there was a significant increase in confidence scores matched by trainee (p < 0.001). Approximately 92.9% and 100% of trainees and experts were in favor of using the models for assessment and future training respectively. CONCLUSIONS: Our study demonstrates that the CMPT MK 2-Advanced models have high "face validity" and may be a valuable tool for surgical education. The use of these models should be explored for use in the curriculum at medical school.

NMR-based evaluation of the metabolic profile and response to dichloroacetate of human prostate cancer cells.

The aim of this study was to evaluate the metabolic profile of human prostate cancer cells that have different metastatic potential and to determine their response to dichloroacetate (DCA) using NMR technology. Two isogenic human prostate cancer cell lines, differing in their metastatic potential [LNCaP (poorly metastatic) and LNCaP-LN3 (highly metastatic)], were studied. Metabolite ratios from NMR spectral integrals acquired at a field strength of 9.4 T using a 5-mm broadband probe with an NMR-compatible bioreactor were compared in the presence and absence of the pyruvate dehydrogenase kinase inhibitor DCA. Lactate dehydrogenase (LDH) isoenzymes were assessed by zymography. Following the treatment of cells with 50 mm DCA, there was a significant reduction in the lactate/choline, lactate/creatine, lactate/alanine and the combined lactate/(choline + creatine + alanine) ratios in LNCaP-LN3 cells relative to LNCaP cells. No significant changes in metabolite ratios were found in LNCaP cells following DCA treatment. As expected, LDH zymography assays showed an absence of the LDH-B subunit in LNCaP-LN3 cells, whereas both LDH-A and LDH-B subunits were present in LNCaP cells. DCA was shown to significantly modify the metabolite ratios in highly metastatic LNCaP-LN3 cells, but not in poorly metastatic LNCaP cells. This effect was probably related to the absence of the LDH-B subunit in LNCaP-LN3 cells, and could have a bearing on cancer treatment with DCA and related compounds.