Time trends in service provision and survival outcomes for patients with renal cancer treated by nephrectomy in England 2000-2010.

OBJECTIVE: To describe the temporal trends in nephrectomy practice and outcomes for English patients with renal cell carcinoma (RCC). PATIENTS AND METHODS: Adult RCC nephrectomy patients treated between 2000 and 2010 were identified in the National Cancer Data Repository and Hospital Episode Statistics, and followed-up until date of death or 31 December 2015 (n = 30 763). We estimated the annual frequency for each nephrectomy type, the hospital and surgeon numbers and their case volumes. We analysed short-term surgical outcomes, as well as 1- and 5-year relative survivals. RESULTS: Annual RCC nephrectomy number increased by 66% during the study period. Hospital number decreased by 24%, whilst the median annual hospital volume increased from 10 to 23 (P < 0.01). Surgeon number increased by 27% (P < 0.01), doubling the median consultant number per hospital. The proportion of minimally invasive surgery (MIS) nephrectomies rose from 1% to 46%, whilst the proportion of nephron-sparing surgeries (NSS) increased from 5% to 16%, with 29% of all T1 disease treated with partial nephrectomy in 2010 (P < 0.01). The 30-day mortality rate halved from 2.4% to 1.1% and 90-day mortality decreased from 4.9% to 2.6% (P < 0.01). The 1-year relative survival rate increased from 86.9% to 93.4%, whilst the 5-year relative survival rate rose from 68.2% to 81.2% (P < 0.01). Improvements were most notable in patients aged ≥65 years and those with T3 and T4 disease. CONCLUSIONS: Surgical RCC management has changed considerably with nephrectomy centralisation and increased NSS and MIS. In parallel, we observed significant improvements in short- and long-term survival particularly for elderly patients and those with locally advanced disease

Recent Advances in Infrared Nonlinear Optical Crystal

The search and growth of nonlinear optical (NLO) crystals in the infrared (IR) area are significant and of high importance in the fields of NLO, signal communication, solid-state chemistry, and laser frequency conversion. Infrared NLO crystals have a wide IR transparent range, high laser damage threshold (LDT) value, and large NLO coefficients. This chapter presents the recent advances in IR-NLO crystals and especially emphasizes their crystal growth method, crystal structures, band gap value, LDT, and NLO properties. Based on its structural variety, it is categorized into chalcogenides, chalcohalides, oxides, halides, and oxyhalides. This chapter describes several kinds of IR-NLO crystals and their structural, band gap value, thermal, optical, LDT, and NLO properties and also describes the significance of these crystals in laser frequency conversion, optical parameter oscillator, and other optical applications

Impact of Hospital Nephrectomy Volume on Intermediate to Long-term Survival in Renal Cell Carcinoma

OBJECTIVE To evaluate the relationship between hospital volume and intermediate and long-term patient survival for patients undergoing nephrectomy for renal cell carcinoma (RCC). PATIENTS & METHODS Adult RCC patients treated with nephrectomy between 2000 and 2010 were identified from the English Hospital Episode Statistics and National Cancer Data Repository. Patients with nodal or metastatic disease were excluded. Hospitals were categorised into low (<20/yr), medium (20-39/yr) and high (40/yr) volume based on annual cases of RCC nephrectomy. Multivariable Cox regressions were used to calculate hazard ratios for all-cause mortality by hospital volume, adjusting for patient, tumour and surgical characteristics. We assessed conditional survival over three follow-up periods: short (30d-1yr), intermediate (1-3yr) and long (3-5yr). We additionally explored whether associations between volume and outcomes varied by tumour stage. RESULTS 12,912 patients were included. Patients in high volume hospitals had 34% reduction in mortality risks up to one year compared to those in low volume hospitals (HR 0.66, 95% CI 0.53-0.83, p<0.01). Assuming causality, treatment in high volume hospitals was associated with one fewer death in every 71 patients treated. Benefit of nephrectomy centralisation did not change with higher T stage (p=0.17). No significant association between hospital volume and survival was observed beyond the first year. CONCLUSIONS RCC nephrectomy in high volume hospitals was associated with improved survival for up to one year after treatment. Our results contribute new insights regarding the value of nephrectomy centralisation.The Urology Foundation Addenbrooke's Charitable Trust Royal College of Surgeons of Englan

Strategies adopted by men to deal with uncertainty and anxiety when following an active surveillance/monitoring protocol for localised prostate cancer and implications for care: a longitudinal qualitative study embedded within the ProtecT trial.

OBJECTIVES: Active surveillance (AS) enables men with low risk, localised prostate cancer (PCa) to avoid radical treatment unless progression occurs; lack of reliable AS protocols to determine progression leaves uncertainties for men and clinicians. This study investigated men's strategies for coping with the uncertainties of active monitoring (AM, a surveillance strategy within the Prostate testing for cancer and Treatment, ProtecT trial) over the longer term and implications for optimising supportive care. DESIGN: Longitudinal serial in-depth qualitative interviews every 2-3 years for a median 7 (range 6-14) years following diagnosis. SETTING: Four centres within the UK Protect trial. PARTICIPANTS: Purposive sample of 20 men with localised PCa: median age at diagnosis 64 years (range 52-68); 15 (75%) had low-risk PCa; 12 randomly allocated to, 8 choosing AM. Eleven men continued with AM throughout the study period (median 7 years). Nine received radical treatment after a median 4 years (range 0.8-13.8 years). INTERVENTION: AM: 3-monthly serum prostate-specific antigen (PSA)-level assessment (year 1), 6-12 monthly thereafter; increase in PSA ≥50% during previous 12 months or patient/clinician concern triggered review. MAIN OUTCOMES: Thematic analysis of 73 interviews identified strategies to accommodate uncertainty and anxiety of living with untreated cancer; implications for patient care. RESULTS: Men sought clarity, control or reassurance, with contextual factors mediating individual responses. Trust in the clinical team was critical for men in balancing anxiety and facilitating successful management change/continued monitoring. Only men from ProtecT were included; men outside ProtecT may have different experiences. CONCLUSION: Men looked to clinicians for clarity, control and reassurance. Where provided, men felt comfortable continuing AM or having radical treatments when indicated. Clinicians build patient trust by clearly describing uncertainties, allowing patients control wherever possible and being aware of how context influences individual responses. Insights indicate need for supportive services to build trust and patient engagement over the long term. TRIAL REGISTRATION NUMBER: ISRCTN20141297; Pre-results

Infliximab for the treatment of intravenous immunoglobulin resistant Kawasaki disease complicated by coronary artery aneurysms: a case report

This case report describes an 8 year old boy with IVIG resistant Kawasaki disease complicated by severe bilateral coronary artery aneurysms successfully treated with infliximab, a monoclonal antibody against tumour necrosis factor alpha

Proactive vaccination using multiviral Quartet Nanocages to elicit broad anti-coronavirus responses

Defending against future pandemics requires vaccine platforms that protect across a range of related pathogens. Nanoscale patterning can be used to address this issue. Here, we produce quartets of linked receptor-binding domains (RBDs) from a panel of SARS-like betacoronaviruses, coupled to a computationally designed nanocage through SpyTag/SpyCatcher links. These Quartet Nanocages, possessing a branched morphology, induce a high level of neutralizing antibodies against several different coronaviruses, including against viruses not represented in the vaccine. Equivalent antibody responses are raised to RBDs close to the nanocage or at the tips of the nanoparticle’s branches. In animals primed with SARS-CoV-2 Spike, boost immunizations with Quartet Nanocages increase the strength and breadth of an otherwise narrow immune response. A Quartet Nanocage including the Omicron XBB.1.5 ‘Kraken’ RBD induced antibodies with binding to a broad range of sarbecoviruses, as well as neutralizing activity against this variant of concern. Quartet nanocages are a nanomedicine approach with potential to confer heterotypic protection against emergent zoonotic pathogens and facilitate proactive pandemic protection

Discovery of PTN as a serum-based biomarker of pro-metastatic prostate cancer.

Distinguishing clinically significant from indolent prostate cancer (PC) is a major clinical challenge. We utilised targeted protein biomarker discovery approach to identify biomarkers specific for pro-metastatic PC. Serum samples from the cancer-free group; Cambridge Prognostic Group 1 (CPG1, low risk); CPG5 (high risk) and metastatic disease were analysed using Olink Proteomics panels. Tissue validation was performed by immunohistochemistry in a radical prostatectomy cohort (n = 234). We discovered that nine proteins (pleiotrophin (PTN), MK, PVRL4, EPHA2, TFPI-2, hK11, SYND1, ANGPT2, and hK14) were elevated in metastatic PC patients when compared to other groups. PTN levels were increased in serum from men with CPG5 compared to benign and CPG1. High tissue PTN level was an independent predictor of biochemical recurrence and metastatic progression in low- and intermediate-grade disease. These findings suggest that PTN may represent a novel biomarker for the presence of poor prognosis local disease with the potential to metastasise warranting further investigation

The ProtecT randomised trial cost-effectiveness analysis comparing active monitoring, surgery, or radiotherapy for prostate cancer

Abstract: Background: There is limited evidence relating to the cost-effectiveness of treatments for localised prostate cancer. Methods: The cost-effectiveness of active monitoring, surgery, and radiotherapy was evaluated within the Prostate Testing for Cancer and Treatment (ProtecT) randomised controlled trial from a UK NHS perspective at 10 years’ median follow-up. Prostate cancer resource-use collected from hospital records and trial participants was valued using UK reference-costs. QALYs (quality-adjusted-life-years) were calculated from patient-reported EQ-5D-3L measurements. Adjusted mean costs, QALYs, and incremental cost-effectiveness ratios were calculated; cost-effectiveness acceptability curves and sensitivity analyses addressed uncertainty; subgroup analyses considered age and disease-risk. Results: Adjusted mean QALYs were similar between groups: 6.89 (active monitoring), 7.09 (radiotherapy), and 6.91 (surgery). Active monitoring had lower adjusted mean costs (£5913) than radiotherapy (£7361) and surgery (£7519). Radiotherapy was the most likely (58% probability) cost-effective option at the UK NICE willingness-to-pay threshold (£20,000 per QALY). Subgroup analyses confirmed radiotherapy was cost-effective for older men and intermediate/high-risk disease groups; active monitoring was more likely to be the cost-effective option for younger men and low-risk groups. Conclusions: Longer follow-up and modelling are required to determine the most cost-effective treatment for localised prostate cancer over a man’s lifetime. Trial registration: Current Controlled Trials number, ISRCTN20141297: http://isrctn.org (14/10/2002); ClinicalTrials.gov number, NCT02044172: http://www.clinicaltrials.gov (23/01/2014)

Ten-year mortality, disease progression, and treatment-related side effects in men with localised prostate cancer from the ProtecT randomised controlled trial according to treatment received

Background The ProtecT trial reported intention-to-treat analysis of men with localised prostate cancer randomly allocated to active monitoring (AM), radical prostatectomy, and external beam radiotherapy. Objective To report outcomes according to treatment received in men in randomised and treatment choice cohorts. Design, setting, and participants This study focuses on secondary care. Men with clinically localised prostate cancer at one of nine UK centres were invited to participate in the treatment trial comparing AM, radical prostatectomy, and radiotherapy. Intervention Two cohorts included 1643 men who agreed to be randomised and 997 who declined randomisation and chose treatment. Outcome measurements and statistical analysis Analysis was carried out to assess mortality, metastasis and progression and health-related quality of life impacts on urinary, bowel, and sexual function using patient-reported outcome measures. Analysis was based on comparisons between groups defined by treatment received for both randomised and treatment choice cohorts in turn, with pooled estimates of intervention effect obtained using meta-analysis. Differences were estimated with adjustment for known prognostic factors using propensity scores. Results and limitations According to treatment received, more men receiving AM died of PCa (AM 1.85%, surgery 0.67%, radiotherapy 0.73%), whilst this difference remained consistent with chance in the randomised cohort (p = 0.08); stronger evidence was found in the exploratory analyses (randomised plus choice cohort) when AM was compared with the combined radical treatment group (p = 0.003). There was also strong evidence that metastasis (AM 5.6%, surgery 2.4%, radiotherapy 2.7%) and disease progression (AM 20.35%, surgery 5.87%, radiotherapy 6.62%) were more common in the AM group. Compared with AM, there were higher risks of sexual dysfunction (95% at 6 mo) and urinary incontinence (55% at 6 mo) after surgery, and of sexual dysfunction (88% at 6 mo) and bowel dysfunction (5% at 6 mo) after radiotherapy. The key limitations are the potential for bias when comparing groups defined by treatment received and changes in the protocol for AM during the lengthy follow-up required in trials of screen-detected PCa. Conclusions Analyses according to treatment received showed increased rates of disease-related events and lower rates of patient-reported harms in men managed by AM compared with men managed by radical treatment, and stronger evidence of greater PCa mortality in the AM group. Patient summary More than 95 out of every 100 men with low or intermediate risk localised prostate cancer do not die of prostate cancer within 10 yr, irrespective of whether treatment is by means of monitoring, surgery, or radiotherapy. Side effects on sexual and bladder function are better after active monitoring, but the risks of spreading of prostate cancer are more common

Sequencing of prostate cancers identifies new cancer genes, routes of progression and drug targets

Prostate cancer represents a substantial clinical challenge because it is difficult to predict outcome and advanced disease is often fatal. We sequenced the whole genomes of 112 primary and metastatic prostate cancer samples. From joint analysis of these cancers with those from previous studies (930 cancers in total), we found evidence for 22 previously unidentified putative driver genes harboring coding mutations, as well as evidence for NEAT1 and FOXA1 acting as drivers through noncoding mutations. Through the temporal dissection of aberrations, we identified driver mutations specifically associated with steps in the progression of prostate cancer, establishing, for example, loss of CHD1 and BRCA2 as early events in cancer development of ETS fusion-negative cancers. Computational chemogenomic (canSAR) analysis of prostate cancer mutations identified 11 targets of approved drugs, 7 targets of investigational drugs, and 62 targets of compounds that may be active and should be considered candidates for future clinical trials