Attempted suicide: does lethality matter?

OBJECTIVES: To investigate whether high-lethality suicide attempters align to the demographic and clinical features observed in completed suicide in the national and international literature, and whether low-lethality attempters more closely align with the clinical profile of non-attempter ideators. METHODS: A retrospective chart review of adult suicide ideators and attempters presenting to an urban tertiary care hospital was performed. Suicide ideators (n = 50) and attempters (n = 50) were coded for variables including demographics and clinical characteristics (e.g. psychiatric diagnosis and previous suicide attempt). Method and lethality of suicide attempt were coded using the medical Lethality Rating Scale. RESULTS: High-lethality attempters were more likely to be younger in age than low-lethality attempters (p = 0.026) and ideators (p = 0.041). The lethality scores of suicide attempts were significantly inversely correlated with age (p = 0.017). CONCLUSIONS: Our study adds to the small but increasing body of literature investigating the characteristics of high-lethality suicide attempters and suggests younger adult age is a risk factor for a high-lethality attempt. Further understanding of this unique group would be aided by widespread agreement on the definition of a high-lethality suicide attempt and longitudinal studies of this cohort.

Surgical innovation revisited: A historical narrative of the minimally invasive "Agarwal sliding-clip renorrhaphy" technique for partial nephrectomy and its application to an Australian cohort.

Objective: To evaluate local clinical outcomes of sliding clip renorrhaphy, from inception to current utilization for open, laparoscopic, and robotically assisted partial nephrectomy. Methods: We reviewed prospectively maintained databases of three surgeons performing partial nephrectomies with the sliding-clip technique at teaching hospitals between 2005 and 2019. Baseline characteristics, operative parameters, including surgical approach, RENAL Nephrometry Score, and post-operative outcomes, including Clavien-Dindo classification of complications, were recorded for 76 consecutive cases. We compared perioperative and 90-day events with patient and tumor characteristics, stratified by operative approach and case complexity, using Wilcoxon rank-sum test for continuous variables and the Chi-squared or Fisher's exact test, for binary and categorical variables, respectively. Results: Open surgery (n = 15) reduced ischemia time and operative time, but increased hospital admission time. Pre- and post-operative estimated glomerular filtration rates did not change significantly by operative approach. Older patients (P = .007) and open surgery (P = .003) were associated with a higher rate of complications (any-grade). Six grade ≥3 complications occurred: these were associated with higher RENAL Nephrometry Score (P = .016) and higher pathological tumor stage (P = .045). Limits include smaller case volumes which incorporate the learning curve cases; therefore, these data are most applicable to lower volume teaching hospitals. Conclusion: The sliding-clip technique for partial nephrectomy was first described by Agarwal et al and has low complication rates, acceptable operative time, and preserves renal function across open and minimally invasive surgeries. This series encompasses the initial learning curve with developing the technique through to present-day emergence as a routine standard of practice.

Evaluation of models predicting insignificant prostate cancer to select men for active surveillance of prostate cancer.

BACKGROUND: In an era of personalized medicine, individualized risk assessment using easily available tools on the internet and the literature are appealing. However, uninformed use by clinicians and the public raises potential problems. Herein, we assess the performance of published models to predict insignificant prostate cancer (PCa), using a multi-national low-risk population that may be considered for active surveillance (AS) based on contemporary practice. METHODS: Data on men suitable for AS but undergoing upfront radical prostatectomy were pooled from three international academic institutions in Cambridge (UK), Toronto (Canada) and Melbourne (Australia). Four predictive models identified from literature review were assessed for their ability to predict the presence of four definitions of insignificant PCa. Evaluation was performed using area under the curve (AUC) of receiver operating characteristic curves and Brier scores for discrimination, calibration curves and decision curve analysis. RESULTS: A cohort of 460 men meeting the inclusion criteria of all four nomograms was identified. The highest AUCs calculated for any of the four models ranged from 0.618 to 0.664, suggesting weak positive discrimination at best. Models had best discriminative ability for a definition of insignificant disease characterized by organ-confined Gleason score ⩽6 with a total volume ⩽0.5 ml or 1.3 ml. Calibration plots showed moderate range of predictive ability for the Kattan model though this model did not perform well at decision curve analysis. CONCLUSIONS: External assessment of models predicting insignificant PCa showed moderate performance at best. Uninformed interpretation may cause undue anxiety or false reassurance and they should be used with caution.

International multicentre study examining selection criteria for active surveillance in men undergoing radical prostatectomy.

BACKGROUND: The controversies concerning possible overtreatment of prostate cancer, highlighted by debate over PSA screening, have highlighted active surveillance (AS) as an alternative management option for appropriate men. Regional differences in the underlying prevalence of PSA testing may alter the pre-test probability for high-risk disease, which can potentially interfere with the performance of selection criteria for AS. In a multicentre study from three different countries, we examine men who were initially suitable for AS according to the Toronto and Prostate Cancer Research International: Active Surveillance (PRIAS) criteria, that underwent radical prostatectomy (RP) in regards to:1.the proportion of pathological reclassification(Gleason score ≥7, ≥pT3 disease),2.predictors of high-risk disease,3.create a predictive model to assist with selection of men suitable for AS. METHODS: From three centres in the United Kingdom, Canada and Australia, data on men who underwent RP were retrospectively reviewed (n=2329). Multivariable logistic regression was performed to identify predictors of high-risk disease. A nomogram was generated by logistic regression analysis, and performance characterised by receiver operating characteristic curves. RESULTS: For men suitable for AS according to the Toronto (n=800) and PRIAS (410) criteria, the rates for upgrading were 50.6, 42.7%, and upstaging 17.6, 12.4%, respectively. Significant predictors of high-risk disease were:•Toronto criteria: increasing age, cT2 disease, centre of diagnosis and number of positive cores.•PRIAS criteria: increasing PSA and cT2 disease.Cambridge had a high pT3a rate (26 vs 12%). To assist selection of men in the United Kingdom for AS, from the Cambridge data, we generated a nomogram predicting high-risk features in patients who meet the Toronto criteria (AUC of 0.72). CONCLUSION: The proportion of pathological reclassification in our cohort was higher than previously reported. Care must be used when applying the AS criteria generated from one population to another. With more stringent selection criteria, there is less reclassification but also fewer men who may benefit from AS.

Levels of a subpopulation of platelets, but not circulating endothelial cells, predict early treatment failure in prostate cancer patients after prostatectomy.

BACKGROUND: Angiogenesis is one of the hallmarks of cancer driving tumour growth and ultimately metastasis. Circulating endothelial cells (CECs) and circulating endothelial progenitor (CEPs) cells have been reported as candidate surrogate markers for tumour vascularisation. Our aim was to investigate the potential use of these circulating cells levels as predictors of prostate cancer treatment failure and metastasis. METHODS: We examined the levels of CD31(+)CD45(-) cells (CECs) and CD31(+)CD45(-)CD117(+) (CEPs) in s.c. and orthotopic models of human prostate cancers and correlated measurements with tumour size, volume and microvessel density (MVD). We then performed a prospective cohort study in 164 men with localised prostate cancer undergoing prostatectomy. The CD31(+)CD45(-), CD31(+)CD45(-)CD146(+) (CECs) and CD31(+)CD45(intermediate)CD133(+) (CEPs) populations were quantified and subsequently enriched for further characterisation. RESULTS: In preclinical models, levels of CD31(+)CD45(-) cells, but not CEPs, were significantly elevated in tumour-bearing mice and correlated with tumour size, volume and MVD. In our human prospective cohort study, the levels of CD31(+)CD45(-) cells were significantly higher in men who experienced treatment failure within the first year, and on logistic regression analysis were an independent predictor of treatment failure, whereas neither levels of CECs or CEPs had any prognostic utility. Characterisation of the isolated CD31(+)CD45(-) cell population revealed an essentially homogenous population of large, immature platelets representing <0.1% of circulating platelets. CONCLUSION: Elevated levels of a distinct subpopulation of circulating platelets were an independent predictor for early biochemical recurrence in prostate cancer patients within the first year from prostatectomy.

Open-label, phase I dose-escalation study of sodium selenate, a novel activator of PP2A, in patients with castration-resistant prostate cancer.

BACKGROUND: Angiogenesis is fundamental to the progression of many solid tumours including prostate cancer. Sodium selenate is a small, water-soluble, orally bioavailable activator of PP2A phosphatase with anti-angiogenic properties. METHODS: This was a dose-escalation phase I study in men with asymptomatic, chemotherapy-naïve, castration-resistant prostate cancer. The primary objective was to determine the maximum tolerated dose (MTD). Secondary objectives included establishing the safety, tolerability and pharmacokinetic profile. RESULTS: A total of 19 patients were enrolled. The MTD was 60 mg per day. Dose-limiting toxicity (fatigue and diarrhoea) was observed at 90 mg per day. The most frequently reported treatment-related adverse events across all treatment cohorts were nausea, diarrhoea, fatigue, muscle spasms, alopecia and nail disorders. No grade 4 toxicities were observed and there were no deaths on study. Linear pharmacokinetics was observed. One patient had a PSA response >50%. Median time to PSA progression (for non-responders) was 14.2 weeks. Mean PSA doubling time increased during the main treatment phase from 2.18 months before trial to 3.85 months. CONCLUSION: Sodium selenate is well tolerated at a dose of 60 mg per day with modest single-agent efficacy similar to other anti-angiogenic agents. Further trials in combination with conventional cytotoxic regimens are warranted.

Prostate cancer: how aware is the public?

OBJECTIVE: To assess the public awareness of prostate cancer and willingness to seek medical attention for urinary symptoms, and to determine associated factors. SUBJECTS AND METHODS: A community survey was conducted using a questionnaire administered by the interviewer to 280 randomly selected Irish men aged 40-69 years. RESULTS: A quarter of the men had not heard of prostate cancer; factors associated with having heard were nonmanual social class, living with a female partner and a history of treatment for urinary disease. Eighty per cent said they would be willing to attend a GP if they had urinary symptoms; associated factors were living with a female partner, having heard of prostate cancer and having seen a GP more than once in the preceding year. Just over half deemed attendance to be urgent/important; associated factors were having heard of prostate cancer, living with a female partner and having a relative with cancer. Having a General Medical Services card (a means-tested medical card entitling the holder to free medical services) was negatively associated. Lower social class was negatively associated with routine questioning by a GP about urinary symptoms. CONCLUSIONS: There is a marked social-class gradient in knowledge and willingness to seek medical advice. In the absence of population screening, earlier clinical presentation with prostate cancer is essential if prognosis is to be improved; there is an evident need to improve prostate cancer awareness, particularly in the lower social classes, if this goal is to be achieved.

Cancer of the pyriform fossa: hyperfractionated radiotherapy as a primary treatment modality.

Carcinoma of the pyriform fossa carries one of the worst prognoses of all head and neck cancers. A prospective trial was set up to study the efficacy of hyperfractionated radiotherapy as a primary treatment modality in the management of these patients. Seventeen patients entered the trial and were followed for up to 3 years. Results for local control, regional control and survival compare favourably with patients treated primarily with surgery with or without radiotherapy. Hyperfractionated radiotherapy offers a logical and standardized approach to the management of this tumour and reduces the significant morbidity associated with the use of surgery as a primary treatment.

Prepubertal melanoma.

Malignant melanoma is an uncommon tumor in childhood. We report a case of prepubertal melanoma occurring in a 10-year-old girl and comment on the difficulties encountered in the diagnosis and management of this condition.