LOT and HOT or not. The proliferation of clinically insignificant and poorly characterised types of renal neoplasia.

The classification of malignant tumours is influenced by both immunohistochemical and molecular genetic findings. This is highlighted in the latest World Health Organization classification of renal neoplasia, which has a tumour category of 'tumours that are molecularly defined'. This implies that the defining molecular features are integral to tumourigenesis, which may not necessarily be the case. Renal oncocytoma is recognised as a benign tumour with variable morphology and immunoexpression. A variant of these tumours is hybrid oncocytic chromophobe tumour, which has features of both oncocytoma and chromophobe renal cell carcinoma and may, on rare occasions, show malignant behaviour. Recent reports have proposed two further entities with eosinophilic cytoplasm and varying nuclear pleomorphism, designated low grade oncocytic tumour (LOT) and eosinophilic vacuolated tumour (EVT), formally known as high grade oncocytic tumour (HOT). The diagnosis of these apparently benign tumours was made on the basis of morphological and immunohistochemical features. More recently it has been claimed that the mutations in the mTOR pathway are also a diagnostic feature and it is further suggested that these mutations are key to the pathogenesis of these tumours. As is seen in oncocytoma, immunohistochemical expression of tumours included in series of LOT and EVT is variable. The mutations in the mTOR pathway, where detected, were not constant, with any combination of mTOR, TSC1 and/or TSC2 being involved. A major issue is that in many of the studies full comparative genomic hybridisation results are not presented. In addition it is well recognised that mTOR mutations are seen in a variety of renal tumours. In view of these conflicting results, the rarity of these tumours and their apparent benign nature, raises questions as to why these tumours should be considered specific entities.

Improving mental health literacy in year 9 high school children across Wales: a protocol for a randomised control treatment trial (RCT) of a mental health literacy programme across an entire country.

BACKGROUND: Adolescence is a crucial period for developing and maintaining good habits for mental health and well-being. This is important for future mental health, as most mental health problems manifest during adolescence. Mental health literacy is the foundation for mental health prevention, stigma reduction, and increased help-seeking efficacy particularly among adolescents. The mental health literacy programme "The Guide", which was developed in Canada, has shown success in increasing mental health literacy in North American 16-17 year olds. "The Guide Cymru" is an adaptation of The Guide designed for a younger age group (13-14 year olds) and for the Welsh culture and context and is being offered to all state schools in Wales. METHODS: This two-armed cluster randomised control trial (RCT) will evaluate the effectiveness of The Guide Cymru. All 205 secondary schools in Wales will be invited to take part, involving up to 30,000 year 9 pupils. Schools will be randomised to either the immediate implementation of The Guide Cymru or to a wait-list control. The wait-list control will receive The Guide Cymru around 12 weeks later. Measures of mental health literacy (assessed via the Knowledge and Attitudes to Mental Health scale) and mental health problems (via the PedsQL and Strengths and Difficulties Questionnaire) will be taken at baseline (pre-intervention), 12 weeks later (after the active group has received The Guide Cymru), and 24 weeks later (after the wait-list control has received The Guide Cymru). DISCUSSION: The trial aims to evaluate if The Guide Cymru increases mental health literacy, including reduced stigma to others and to the self, and increased levels of good mental health behaviours and help-seeking for mental health problems. TRIAL REGISTRATION: ISRCTN15462041. Registered 03/10/2019.

Improved lower urinary tract symptoms after robot-assisted radical prostatectomy: implications for survivorship, treatment selection and patient counselling.

OBJECTIVE: To assess changes in lower urinary tract symptoms (LUTS) and quality of life (QoL) after robot-assisted radical prostatectomy (RARP). PATIENTS AND METHODS: A prospectively curated database of 1917 consecutive RARPs undertaken over an 8-year period from January 2009 to January 2017 was assessed. Preoperative information including age, prostate-specific antigen (PSA) level, body mass index (BMI), International Prostate Symptom Score (IPSS) and QoL score was collected, with IPSS and QoL score compared between baseline (preoperatively) and 12 months post-surgery. RESULTS: Of the 1917 patients who underwent RARP, 1470 with complete data were included in the analysis. Their mean ± sd age, prostate weight and BMI were 62 (±6.7) years, 51 (±17.6) g, and 28 kg/m2 , respectively. Overall, 57% of patients reported an improved IPSS score, whilst 76% reported an IPSS of ≤7 postoperatively. A total of 41% of patients reported an improved QoL and 90.3% of patients with severe preoperative LUTS (IPSS 20-35) demonstrated clinically improved LUTS at 1 year post RARP. The post-RARP mean IPSS in the present study was lower than those reported in the existing post-radiotherapy literature, especially in patients with moderate to severe baseline LUTS (IPSSs ≥ 8). CONCLUSIONS: At 12 months post RARP, most patients reported improved overall LUTS and QoL, with the greatest benefit seen in those patients with a high pre-RARP IPSS. This has implications for treatment selection and preoperative counselling in men being offered active treatment for their prostate cancer. Further analyses of specific IPSS domains and longer follow-up are needed.

Assessment of tumour-associated necrosis provides prognostic information additional to World Health Organization/International Society of Urological Pathology grading for clear cell renal cell carcinoma.

AIMS: The aims of this study were to evaluate the impact of tumour-associated necrosis (TAN) on metastasis-free survival for clear cell renal cell carcinoma (RCC), and to determine whether TAN provides survival information additional to World Health Organization (WHO)/International Society of Urological Pathology (ISUP) grading. METHODS AND RESULTS: The study consisted of 376 cases of clear cell RCC treated by nephrectomy, for which follow-up was available. WHO/ISUP grade was assigned, and sections were assessed for the presence of TAN. American Joint Committee on Cancer (AJCC) pT staging category and tumour size were also recorded. The development of metastatic disease was taken as the clinical endpoint, and survival analyses, utilising univariate and multivariate models, were performed. WHO/ISUP grades were: grade 1, 35 cases (9.3%); grade 2, 188 cases (50.0%); grade 3, 91 cases (24.2%); and grade 4, 62 cases (16.5%). Staging categories were pT1-pT2 [234 tumours (62.2%)] and pT3-pT4 [139 tumours (37.0%)]. TAN was seen in 128 cases (34.0%). Neither TAN nor metastases were seen in grade 1 tumours. Among grade 2-4 tumours, those with TAN had a significantly worse prognosis than those without TAN (P = 0.017, P = 0.04, and P = 0.006, respectively). Multivariate analysis (WHO/ISUP grade, pT staging category, and TAN) showed all three variables to be independently associated with outcome (P = 0.009, P = 0.005, and P = 0.001, respectively). For all tumour grades and pT staging categories, it was found that the presence of TAN was associated with a 2.91-fold greater risk of metastatic disease. CONCLUSION: Tumour-associated necrosis is an important prognostic factor for clear cell RCC, independently of WHO/ISUP grade. This supports the suggestion that TAN could be incorporated into tumour grading criteria.

Clear cell renal cell carcinoma: validation of World Health Organization/International Society of Urological Pathology grading.

AIMS: In 2012, the International Society of Urological Pathology (ISUP) introduced a novel grading system for clear cell renal cell carcinoma (ccRCC) and papillary renal cell carcinoma. This system is incorporated into the latest World Health Organization renal tumour classification, being designated WHO/ISUP grading. This study was undertaken to compare WHO/ISUP and Fuhrman grading and to validate WHO/ISUP grading as a prognostic parameter in a series of clear cell RCC. METHODS AND RESULTS: Analysis of 681 cases of ccRCC showed that 144 tumours could not be assigned a Fuhrman grade on the basis of ambiguous grading features. The application of WHO/ISUP grading resulted in a general down-grading of cases when compared with Fuhrman grading. In a sub-group of 374 cases, for which outcome data were available, 9.3% were WHO/ISUP grade 1, 50.3% were grade 2, 24.1% grade 3 and 16.3% grade 4, while the distribution of Fuhrman grades was 0.4% grade 1, 48.7% grade 2, 29.4% grade 3 and 21.5% grade 4. There were no recurrence/metastases amongst patients with WHO/ISUP grade 1 tumours and there was a significant difference in outcome for WHO/ISUP grades 2, 3 and 4. For Fuhrman grading the cancer-free survival was not significantly different for grade 2 and grade 3 tumours. On multivariate analysis WHO/ISUP grade and pT staging category were found to retain prognostic significance. CONCLUSIONS: The study demonstrates that FG cannot be applied in >20% of cases of ccRCC and the WHO/ISUP provides superior prognostic information.

Pleomorphic giant cell carcinoma of the urinary bladder: an extreme form of tumour de-differentiation.

AIMS: Vesical pleomorphic giant cell carcinoma (PGCC) is a variant of urothelial carcinoma (UC) characterized by highly pleomorphic tumour with giant cells. Fewer than 10 cases have been reported, and our aim was to determine the clinical and pathological features of a series of tumours from a specialized uropathology laboratory. METHODS AND RESULTS: Thirteen cases of PGCC of the bladder were identified. There were nine males and four females, ranging in age from 53 to 92 years (mean 72 years). Associated conventional high-grade UC was seen in eight cases, while three cases also had micropapillary UC and one plasmacytoid UC. UC in situ (CIS) was present in five cases and occasional bizarre cells were seen in both UC and CIS. The proportion of PGCC present varied from 40% to 100% of tumour. Immunostaining performed on 10 cases showed uniform positivity for CK 8/18 and AE1/AE3, while most tumours were positive for CK7, CK20, uroplakin III and GATA binding protein 3 (GATA3). ß-human chorionic gonadotrophin (ß-hCG) was negative. Of 10 patients with follow-up, five died within 1 year and four are alive with tumour. CONCLUSIONS: The association of PGCC with UC and an overlap in immunoexpression suggests that PGCC represents an extreme form of UC de-differentiation.

Advanced regional anesthesia morbidity and mortality grading system: regional anesthesia outcomes reporting (ROAR).

OBJECTIVE: A regional anesthesia complication grading system (regional anesthesia outcomes reporting [ROAR]) was developed and applied to 1,213 consecutive patients over a 14-month period. The goal of the project was the creation of a system to standardize complication reporting in the regional anesthesia literature. DESIGN: Patient demographics, status as a war casualty, regional block procedure-specific details, and complication grade were entered into an Internet-based, encrypted Department of Defense database. Regional anesthesia complications were later graded and subcategorized depending on what phase of the block the procedural adverse event took place. RESULTS: One thousand ninety-eight (90.5%) patients had neither regional anesthesia associated technical difficulties or more severe complications. Of a total of 147 cases with adverse events among 115 patients (1.3 per patient), the majority (63.3%, 93/147) were low-grade complications resulting in no significant morbidity. The most common complications resulting in patient morbidity were failed block requiring catheter removal and/or supplemental block (35.4%, 17/48). High grade complications represented only 4.1% (6/147) of all peri-procedural morbidity. These complications included pneumothorax requiring tube thoracostomy, transient laryngeal nerve dysfunction, and cancellation of planned operation after peripheral nerve block or catheter placement. CONCLUSIONS: The value of the ROAR system is that it identifies important issues in risk management in regional anesthesia, thereby providing opportunities for further investigation and clinical practice refinement. Furthermore, it provides for a common language when reporting outcomes in the regional anesthesia literature. Use of the ROAR system will provide consistency in outcomes reporting and facilitate comparisons between methods and procedures.

The safety of intravenously administered vitamin K.

Literature sources suggest that iv vitamin K is associated with significant adverse side effects. Systematic study and documentation is lacking. In this 2-y retrospective review, 100 sequential doses of iv administered vitamin K in 45 patients were identified by computer-generated pharmacy utilization reports in an adult teaching hospital. Charts were reviewed for complications following infusion of vitamin K, including specific abnormalities during the 90-min period post-administration: systolic blood pressure <90, heart rate <60 or >120, rash, shortness of breath, and syncope. Complete post-administration data were available for 60/100 doses. One episode of clinically insignificant transient hypotension was identified. Progress notes, discharge summaries and a concurrent survey of adverse drug reaction reports identified no complications related to the use of iv vitamin K. In this series, the iv administration of vitamin K did not pose a clinically significant risk.