Influence of Hospital Volume on Nephrectomy Mortality and Complications: A Systematic Review and Meta-analysis Stratified by Surgical Type

Objectives The provision of complex surgery is increasingly centralised to high volume specialist hospitals. Evidence to support nephrectomy centralisation however has been inconsistent. We conducted a systematic review and meta-analysis to determine the association between hospital case volumes and perioperative outcomes in radical nephrectomy, partial nephrectomy and nephrectomy with venous thrombectomy. Methods Medline, Embase and the Cochrane Library were searched for relevant studies published between 1990 and 2016. Pooled effect estimates for nephrectomy mortality and complications were calculated for each nephrectomy type using the DerSimonian and Laird random-effects model. Sensitivity analyses were performed to examine the effects of heterogeneity on the pooled effect estimates by excluding studies with the heaviest weighting, lowest methodological score, and most likely to introduce bias from misclassification of standardised hospital volume. Results Some 226,372 patients from sixteen publications were included in our review and meta-analysis. Considerable between-study heterogeneity was noted and only a few reported volume-outcome relationships specifically in partial nephrectomy or nephrectomy with venous thrombectomy. High volume hospitals were correlated with a 26% and 52% reduction in mortality for radical nephrectomy (OR 0.74, 95% CI 0.61-0.90, p<0.01) and nephrectomy with venous thrombectomy (OR 0.48, 95% CI 0.29-0.81, p<0.01) respectively. In addition, radical nephrectomy in high volume hospitals was associated with an 18% reduction in complications (OR 0.82, 95% CI 0.73-0.92, p<0.01). No significant volume-outcome relationship in mortality (OR 0.84, 95% CI 0.31-2.26, p=0.73) or complications (OR 0.85, 95% CI 0.55-1.30, p=0.44) was observed for partial nephrectomy. Conclusions Our findings suggest that patients undergoing radical nephrectomy have improved outcomes when treated by high volume hospitals. Evidence of this in partial nephrectomy and nephrectomy with venous thrombectomy is however not yet clear and could be secondary to the low number of studies included and the small patient number in our analyses. Further investigation is warranted to establish the full potential of nephrectomy centralisation particularly as existing evidence is of low quality with significant heterogeneity.This work was supported by Addenbrooke’s Charitable Trust, the Royal College of Surgeons of England and the Urology Foundation. Cancer Research UK Advanced Clinician Scientist Fellowship award (No. C18081/A18180) has supported GL and TS

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. This article is protected by copyright. All rights reserved

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

613 cases of splenic rupture without risk factors or previously diagnosed disease: a systematic review

Background Rupture of the spleen in the absence of trauma or previously diagnosed disease is largely ignored in the emergency literature and is often not documented as such in journals from other fields. We have conducted a systematic review of the literature to highlight the surprisingly frequent occurrence of this phenomenon and to document the diversity of diseases that can present in this fashion. Methods Systematic review of English and French language publications catalogued in Pubmed, Embase and CINAHL between 1950 and 2011. Results We found 613 cases of splenic rupture meeting the criteria above, 327 of which occurred as the presenting complaint of an underlying disease and 112 of which occurred following a medical procedure. Rupture appeared to occur spontaneously in histologically normal (but not necessarily normal size) spleens in 35 cases and after minor trauma in 23 cases. Medications were implicated in 47 cases, a splenic or adjacent anatomical abnormality in 31 cases and pregnancy or its complications in 38 cases. The most common associated diseases were infectious (n = 143), haematologic (n = 84) and non-haematologic neoplasms (n = 48). Amyloidosis (n = 24), internal trauma such as cough or vomiting (n = 17) and rheumatologic diseases (n = 10) are less frequently reported. Colonoscopy (n = 87) was the procedure reported most frequently as a cause of rupture. The anatomic abnormalities associated with rupture include splenic cysts (n = 6), infarction (n = 6) and hamartomata (n = 5). Medications associated with rupture include anticoagulants (n = 21), thrombolytics (n = 13) and recombinant G-CSF (n = 10). Other causes or associations reported very infrequently include other endoscopy, pulmonary, cardiac or abdominal surgery, hysterectomy, peliosis, empyema, remote pancreato-renal transplant, thrombosed splenic vein, hemangiomata, pancreatic pseudocysts, splenic artery aneurysm, cholesterol embolism, splenic granuloma, congenital diaphragmatic hernia, rib exostosis, pancreatitis, Gaucher's disease, Wilson's disease, pheochromocytoma, afibrinogenemia and ruptured ectopic pregnancy. Conclusions Emergency physicians should be attuned to the fact that rupture of the spleen can occur in the absence of major trauma or previously diagnosed splenic disease. The occurrence of such a rupture is likely to be the manifesting complaint of an underlying disease. Furthermore, colonoscopy should be more widely documented as a cause of splenic rupture