Background & AimsClassical ferroportin disease is characterized by hyperferritinemia, normal transferrin saturation, and iron overload in macrophages. A non-classical form is characterized by additional hepatocellular iron deposits and a high transferrin saturation. Both forms demonstrate autosomal dominant transmission and are associated with ferroportin gene (SLC40A1) mutations. SLC40A1 encodes a cellular iron exporter expressed in macrophages, enterocytes, and hepatocytes. The aim of the analysis is to determine the penetrance of SLC40A1 mutations and to evaluate in silico tools to predict the functional impairment of ferroportin mutations as an alternative to in vitro studies.MethodsWe conducted a systematic review of the literature and meta-analysis of the biochemical presentation, genetics, and pathology of ferroportin disease.ResultsOf the 176 individuals reported with SLC40A1 mutations, 80 were classified as classical phenotype with hyperferritinemia and normal transferrin saturation. The non-classical phenotype with hyperferritinemia and elevated transferrin saturation was present in 53 patients. The remaining patients had normal serum ferritin or the data were reported incompletely. Despite an increased hepatic iron concentration in all biopsied patients, significant fibrosis or cirrhosis was present in only 11%. Hyperferritinemia was present in 86% of individuals with ferroportin mutations. Bio-informatic analysis of ferroportin mutations showed that the PolyPhen score has a sensitivity of 99% and a specificity of 67% for the discrimination between ferroportin mutations and polymorphisms.ConclusionsIn contrast to HFE hemochromatosis, ferroportin disease has a high penetrance, is genetically heterogeneous and is rarely associated with fibrosis. Non-classical ferroportin disease is associated with a higher risk of fibrosis and a more severe overload of hepatic iron.

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BackgroundA multicentre study was conducted to investigate the impact of sarcopenia as an independent predictor of oncological outcome after radical cystectomy for bladder cancer.MethodsIn total, 500 patients with available digital computed tomography scans of the abdomen obtained within 90 days before surgery were identified. The lumbar skeletal muscle index was measured using pre‐operative computed tomography. Cancer‐specific survival (CSS) and overall survival (OS) were estimated using Kaplan–Meier curves. Predictors of CSS and OS were analysed by univariable and multivariable Cox regression models.ResultsBased on skeletal muscle index, 189 patients (37.8%) were classified as sarcopenic. Patients with sarcopenia were older compared with their counterparts (P = 0.002), but both groups were comparable regarding to gender, comorbidity, tumor, node, metastasis (TNM) stage, and type of urinary diversion (all P > 0.05). In total, 234 (46.8%) patients died, and of these, 145 (29.0%) died because of urothelial carcinoma of the bladder. Sarcopenic patients had significantly worse 5 year OS (38.3% vs. 50.5%; P = 0.002) and 5 year CSS (49.5% vs. 62.3%; P = 0.016) rates compared with patients without sarcopenia. Moreover, sarcopenia was associated independently with both increased all‐cause mortality (hazard ratio, 1.43; 95% confidence interval 1.09–1.87; P = 0.01) and increased cancer‐specific mortality (hazard ratio, 1.42; 95% confidence interval, 1.00–2.02; P = 0.048). Our results are limited by the lack of prospective frailty assessment.ConclusionsSarcopenia has been shown to be an independent predictor for OS and CSS in a large multicentre study with patients undergoing radical cystectomy for bladder cancer.

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Study Type – Prognosis (case series) Level of Evidence 4 What's known on the subject? and What does the study add? The degree of comorbidity significantly affects the course of patients with bladder cancer undergoing radical cystectomy (RC). To our knowledge this is the first study comparing four different comorbidity indices in patients undergoing RC for urothelial carcinoma to assess the best clinical predictors for 90‐day perioperative mortality. We concluded that the ASA score should be the method of choice, as it showed a predictive ability superior to that of ECOG and CCI, and is much easier to generate than the ACE‐27. OBJECTIVE To evaluate which of the following among the Adult Comorbidity Evaluation‐27 (ACE‐27), the Charlson Comorbidity Index (CCI), the Eastern Cooperative Oncology Group performance status (ECOG) and the American Society of Anesthesiologists (ASA) comorbidity scores correlate best with perioperative mortality after radical cystectomy (RC) for urothelial carcinoma (UC) of the bladder. PATIENTS AND METHODS A study was carried out on 555 unselected consecutive patients without neoadjuvant chemotherapy who underwent RC for UC of the bladder from 2000 to 2010 at one of two institutions. Patients' medical records were reviewed retrospectively. We established a defined binary linear progression model based on clinical variables to predict perioperative mortality <90 days after RC (90PM). To this model we added, individually, the comorbidity indices ACE‐27, CCI, ECOG, and ASA to assess their predictive capacity regarding 90PM. RESULTS The overall 90PM was 7.9%. Age (P= 0.01) and clinical distant metastatic tumour stage (P= 0.002) were independent predictors for 90PM in the multivariate analysis. Each of the four investigated comorbidity indices was able to significantly increase the predictive capacity of the basic model: ECOG +13.5%, (odds ratio [OR]: 1.61, P= 0.036; area under the curve [AUC] 74.7), ASA Score +28.3% (OR: 2.19, P= 0.004; AUC 76.1), Charlson Index +12.3% (OR: 1.31, P= 0.047; AUC 73.8) and ACE‐27 + 29.8% (OR: 1.72, P= 0.004; AUC 76.1). CONCLUSIONS ASA and ACE‐27 show a nearly identical clinical predictive value for perioperative mortality. Both scores could be considered for clinical practice. With regard to ease of generation and availability, the ASA score can be regarded as the best instrument.

Trifecta and pentafecta incorporate essential criteria in terms of outcome reporting and might be considered for the improvement of standardized quality assessment after RC for UCB.

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