Integrating cytokines and angiogenic factors and tumour bulk with selected clinical criteria improves determination of prognosis in advanced renal cell carcinoma.

BACKGROUND: In two clinical trials of the vascular endothelial growth factor (VEGF) receptor inhibitor pazopanib in advanced renal cell carcinoma (mRCC), we found interleukin-6 as predictive of pazopanib benefit. We evaluated the prognostic significance of candidate cytokines and angiogenic factors (CAFs) identified in that work relative to accepted clinical parameters. METHODS: Seven preselected plasma CAFs (interleukin-6, interleukin-8, osteopontin, VEGF, hepatocyte growth factor, tissue inhibitor of metalloproteinases (TIMP-1), and E-selectin) were measured using multiplex ELISA in plasma collected pretreatment from 343 mRCC patients participating in the phase 3 registration trial of pazopanib vs placebo (NCT00334282). Tumour burden (per sum of longest diameters (SLD)) and 10 other clinical factors were also analysed for association with overall survival (OS; based on initial treatment assignment). RESULTS: Osteopontin, interleukin-6, and TIMP-1 were independently associated with OS in multivariable analysis. A model combining the three CAFs and five clinical variables (including SLD) had higher prognostic accuracy than the International Metastatic Renal Cell Carcinoma Database Consortium criteria (concordance-index 0.75 vs 0.67, respectively), and distinguished two groups of patients within the original intermediate risk category. CONCLUSIONS: A prognostic model incorporating osteopontin, interleukin-6, TIMP-1, tumour burden, and selected clinical criteria increased prognostic accuracy for OS determination in mRCC patients.

Comparison of discriminatory power and accuracy of three lung cancer risk models.

BACKGROUND: Three lung cancer (LC) models have recently been constructed to predict an individual's absolute risk of LC within a defined period. Given their potential application in prevention strategies, a comparison of their accuracy in an independent population is important. METHODS: We used data for 3197 patients with LC and 1703 cancer-free controls recruited to an ongoing case-control study at the Harvard School of Public Health and Massachusetts General Hospital. We estimated the 5-year LC risk for each risk model and compared the discriminatory power, accuracy, and clinical utility of these models. RESULTS: Overall, the Liverpool Lung Project (LLP) and Spitz models had comparable discriminatory power (0.69), whereas the Bach model had significantly lower power (0.66; P=0.02). Positive predictive values were highest with the Spitz models, whereas negative predictive values were highest with the LLP model. The Spitz and Bach models had lower sensitivity but better specificity than did the LLP model. CONCLUSION: We observed modest differences in discriminatory power among the three LC risk models, but discriminatory powers were moderate at best, highlighting the difficulty in developing effective risk models.

[Ultrasound investigation in Apulo-Lucano renal echography study group of the Italian Society of Nephrology: a cognitive report]. / Report conoscitivo sull'esecuzione dell'indagine ecografica del Gruppo di Studio di Ecografia Renale della sezione Apulo-Lucana della SIN.

The number of ultrasonography expert consultant Nephrologists is more and more increasing thanks to the contribution that this methodology has brought in both clinical and treatment fields. Up to now, a database of the ultrasonography benefits, as well as the main criteria for the interpretation of the urinary tract echographic examination has not been compiled, yet. We have therefore drawn up and distributed a questionnaire to the consultant nephrologists of the urinary tract echography study group (Apulo-Lucano division). This questionnaire is made up of 27 ultrasonography application and interpretation issues; it aims mainly at creating a common 'language' to reduce the variety of 'descriptors' currently employed by all different specialists and centres involved. 60 consultant nephrologists participated in the study, from the 29 Nephrology and Dialysis O.U.s of Puglia and Basilicata regions, where there is an active echographic service. Data collected show the key role of ultrasonography investigation for all nephrology patients, as high quality and cost efficient test procedure. Moreover, despite the fact that there are differences in echographic examination performance and interpretation, literature data show clearly that it is fundamental to follow general shared principles. The responsibility and task of those specializing in this discipline should be to allow reproduction and comparison of ultrasonographies, also among different operators and centres, and meta studies, i.e. 'a series of comparative studies', which are still very few in number.

Vascular access for haemodialysis: from surgical procedure to an integrated therapeutic approach.

During the past 10 years the type of vascular access for haemodialysis procedures have changed markedly in our centre: more elbow AV fistulae and more central venous catheters are now used. Nevertheless, early referral to nephrologists and availability of central venous catheters and peritoneal dialysis allow elderly people to be admitted for dialysis treatment. Since vascular access for haemodialysis plays a key role in patient well-being, it is mandatory to apply quality assurance criteria to vascular access for haemodialysis surgery. Based on the results of a national survey, in Italy this policy is still in its early stages: monitoring of vascular access differs amongst centres, interventional radiology is used in a differing way, planning of vascular access for haemodialysis in pre-dialysis patients often remains an unsolved problem. According to our initial experience, we propose the use and validation of a quality-index [(minimum success rate) in elective vascular access for haemodialysis surgery], allowing accreditation of a department and a single surgeon for access management. Prevalence of central venous catheters at first dialysis of chronic renal failure patients is also proposed to evaluate the efficiency in access planning. Better knowledge of vascular access management by different teams could eventually lead to definition of guidelines for this 'Cinderella of dialysis'.

[Quality assurance and control of dialysis access]. / VRQ e chirurgia degli accessi dialitici.

Preliminary experience on total quality program in access surgery for dialysis is described; this kind of "border-line" surgery requires peculiar standards, documents and quality indexes. The use of a quality index based on a minimum success rate of 90% in elective access surgery is proposed. In addition, a "cross-index", suitable for quality evaluation of different dialysis sectors at the same time, is expressed. First interventions aimed at the optimal use of resources are described.

[Treatment of post-transplant erythrocytosis: comparison of lisinopril and theophylline]. / Trattamento dell'eritrocitosi post-trapianto: confronto tra lisinopril e teofillina.

OBJECTIVE: The proposal of this study is to compare the efficacy of lisinopril and theophylline, alone or in association, on erythrocytosis in renal-transplanted patients. DESIGN: Prospectic, case-control study. PATIENTS/ENVIRONMENT: 15 inpatients meeting 3 main criteria: 1) ACE therapy for past erythrocytosis, 2) actual erythrocytosis, 3) symptomatic increase of haematocrit (Hct). INTERVENTION: The treatment has been divided into 3 consecutive phases of 30 days each: 1) lisinopril (5 mg/die), 2) theophylline (4 mg/kg/die), 3) association of 2 drugs. MEASUREMENTS: The evaluations were scheduled at the beginning and every month and consisted of renal function control, haemochromocytometric exam, serum level of folates, B12 vitamin and erythropoietin (EPO), iron level, cyclosporinemia, as well as clinic control and adverse events detection. RESULTS: A significative decrease of Hct values and a decrease of serum erythropoietin values was observed in patients treated with lisinopril. Patients treated with theophylline showed a significant reduction of Hct values causing a reduction of erythropoietin serum level in 8/13 patients. Lisinopril and theophylline administered in combination presented a significant decrease of Hct values, while EPO values diminished compared to basal values. CONCLUSIONS: These data showed that lisinopril is a valid therapy for the treatment of posttransplanted patients affected by erythrocytosis and, moreover, has the benefit of antihypertensive action. Theophylline remains an alternative therapy when ACEi are contraindicated. The combination of the 2 drugs doesn't produce additional benefits.

Natural history of nutrition in chronic renal failure.

Dietetic manipulation significantly influences the progression of renal failure in laboratory animals. Clinical results in humans are contradictory. The aim of the study was epidemiological research on a large sample of kidney disease patients to verify whether renal failure influences nutrient intake before dietetic manipulation. Four hundred and forty-one consecutive, non-selected adult patients with renal insufficiency (creatinine 133-963 mumol, mean 301 +/- 178 mumol in male, 288 +/- 156 mumol/l in female) and 43 kidney disease patients without renal failure were enrolled in the prospective study in the period 1988-1995. Interview at the time of the first nephrological check was performed by only one dietician; the record by recall of intake over 7 days with quantitative assessment was collected with the assistance of nutritional dossier and photographic measures. The patients with renal failure consume energy, proteins, lipids and carbohydrates in lesser quantities than the national population of the same geographical area, but the total lipid and monounsaturated fatty acid intake is higher compared with Italian dietary reference values. In patients with renal failure mean protein intake was 1.02 +/- 0.2 g/kg/day in males and 0.96 +/- 0.2 g/kg/day in females; mean lipid intake was 1.10 +/- 0.2 g/kg/day in males and 1.17 +/- 0.3 g/kg/day in females; mean carbohydrate intake was 3.7 +/- 1.1 g/kg/day in males and 3.49 +/- 1 g/kg/day in females. The nutrition alterations observed in chronic renal failure may be a biological adaptation due to neurological changes affecting the sense of taste.