Selection and monitoring of patients with metastatic castration-resistant prostate cancer for treatment with radium-223

Despite the improvement provided by androgenic suppression in the treatment of prostate cancer, most of tumors develop resistance to castration. However, new therapies have demonstrated an increase in patient survival such as radium-223 (Ra-223), an alpha emitter and calcium mimetic with the capability of targeting osteoblastic metastatic lesions. According to results of the ALSYMPCA phase III trial, Ra-223 has demonstrated its activity by improving symptoms and survival of patients with metastatic castration-resistant prostate cancer (mCRPC), symptomatic bone metastases, and no known visceral metastatic disease, without interfering with subsequent treatments. This review examines the key evidence to establish the best patient selection criteria to use Ra-223, how to assess the response to treatment, treatment-related toxicity, and follow-up, but also current research regarding imaging techniques and biomarkers to assess the efficacy of Ra-223. Finally, we briefly describe the clinical trials that are currently ongoing with Ra-223.     

GABA receptors mediate cerebral vasodilation in the unanesthetized goat

The effects of gamma-aminobutyric acid (GABA) and muscimol upon cerebral blood flow were evaluated in the unanesthetized goat. Cerebral blood flow was continuously measured by means of an electromagnetic flow probe chronically implanted on the internal maxillary artery after occlusion and thrombosis of the distal extracerebral vessels. Administration of GABA (1-100 micrograms) directly into the cerebral circulation produced dose-dependent increases in cerebral blood flow, without accompanying systemic effects. Muscimol mimicked the effects of GABA at doses 10 times lower. Administration of picrotoxin (1-3 mg) into the internal maxillary artery did not significantly change cerebral blood flow, but inhibited in a dose-dependent manner the vasodilation induced by GABA. Selective blockade of beta-adrenergic or muscarinic cholinergic receptors by propranolol or atropine, respectively, did not modify the cerebrovascular response to the GABAergic agonists. These results indicate that GABA increases total cerebral blood flow, acting on specific receptor sites in the cerebral blood vessels. The absence of influence of picrotoxin on resting cerebral blood flow suggests that the GABAergic receptors are not tonically activated under physiological conditions.     

Presentation and role of transplantation in adult patients with type 1 primary hyperoxaluria and the I244T AGXT mutation: Single-center experience

Primary hyperoxaluria type 1 (PH1) is a rare genetic disorder characterized by allelic and clinical heterogeneity. We aim to describe the presentation and full single-center experience of the management of PH1 patients bearing the mutation described in our community (I244T mutation+polymorphism P11L). Since 1983, 12 patients with recurrent renal lithiasis have been diagnosed with PH1 and renal failure in the Canary Islands, Spain. Diagnostic confirmation was based on the presence of oxalosis in undecalcified bone or kidney allograft biopsy, reduced alanine:glyoxylate aminotransferase activity in liver biopsy, and blood DNA analysis. Patients underwent different treatment modalities depending on individual clinical circumstances and therapeutic possibilities at the time of diagnosis: hemodialysis, isolated kidney, simultaneous liver-kidney, or pre-emptive liver transplantation. In all cases, the presentation of advanced renal disease was relatively late (>13 years) and no cases were reported during lactancy or childhood. The eight patients treated with hemodialysis or isolated kidney transplantation showed unfavorable evolution leading to death over a variable period of time. In contrast, the four patients undergoing liver transplantation (three liver+kidney and one pre-emptive liver alone) showed favorable long-term allograft and patient survival (up to 12 years follow-up). In conclusion, in this PH1 population, all bearing the I244T mutation, the development of end-stage renal disease was distinctive during late adolescence or adulthood. Our long-term results support pre-emptive liver transplantation at early stages of renal failure, and kidney-liver transplantation for those with advanced renal disease.     

Determination of the dose of dialysis with integrated modules in the same monitor

The "gold standard" method to measure the mass balance achieved during dialysis for a given solute is based on the total dialysate collection. This procedure is unfeasible and too cumbersome. For this reason, alternative methods have been proposed including the urea kinetic modelling (Kt/V), the measurement of effective ionic dialysance (Diascan), and the continuous spent sampling of dialysate (Quantiscan). The aim of this study was to compare the reliability and agreement of these two methods with the formulas proposed by the urea kinetic modelling for measuring the dialysis dose and others haemodialysis parameters. We studied 20 stable patients (16 men/4 women) dialyzed with a monitor equipped with the modules Diascan (DC) and Quantiscan (QC) (Integra. Hospal). The urea distribution volume (VD) was determined using anthropometric data (Watson equation) and QC data. Kt/V value was calculated according to Daurgidas 2nd generation formula corrected for the rebound (eKt/V), and using DC (Kt/VDC) and QC (Kt/VQC) data. The total mass of urea removed was calculated as 37,93 +/- 16 g/session. The VD calculated using Watson equation was 35.7 +/- 6.6 and the VDQC was 35.06 +/- 9.9. And they showed an significative correlation (r:0,82 p < 0.001). The (VDQC-VDWatson) difference was -0.64 +/- 5.8L (ns). Kt/VDC was equivalent to those of eKt/V (1.64 +/- 0.33 and 1.61 +/- 0.26, mean difference -0.02 +/- 0.29). However, Kt/VQC value was higher than eKt/V (1.67 +/- 0.22 and 1.61 +/- 0.26 mean difference 0.06 +/- 0.07 p < 0.01). Both values correlated highly (R2: 0.92 p < 0.001). Urea generation (C) calculated using UCM was 8.75 +/- 3.4 g/24 h and those calculated using QC was 8.64 +/- 3.21 g/24 h. Mean difference 0.10 +/- 1.14 (ns). G calculated by UCM correlated highly with that derived from QC (R2: 0.88 p < 0.001). In conclusion, Kt/VDC and Kt/VQC should be considered as valid measures for dialysis efficiency. However, the limits of agreement between Kt/VQC and eKt/V were closer than Kt/VDC.     

Bilateral necrotizing fasciitis of the breast following quadrantectomy

Necrotizing fasciitis (NF) is a rare and highly lethal soft-tissue infection that involves the skin, subcutaneous tissue, and fascia. Although it can affect any part of the body, the breast is seldom involved. We describe a case of bilateral NF of the breast following elective quadrantectomy, successfully treated with antibiotics, bilateral mastectomy, and a vacuum-assisted wound closure system.     

Perioperative variables associated with surgical site infection in breast cancer surgery

Despite the fact that breast operations are usually categorized as clean procedures, higher surgical site infection (SSI) rates are reported. This study aimed to determine the perioperative variables related to SSI in breast cancer patients. Medical records of breast cancer patients undergoing surgery between January 2005 and August 2007 at a university based hospital were reviewed. Preoperative, intraoperative, and postoperative clinical data from 199 patients were extracted and analysed. Overall, the SSI rate was 19.1% (38 cases). SSI was associated with a high body mass index (P=0.001), history of diabetes mellitus (P<0.0001), smoking (P<0.0001), or active skin disorders (P<0.0001). Other SSI-related variables included a tumour at an advanced clinical stage (P=0.003) and neoadjuvant therapy (P=0.003). Breast-conserving operations were less frequently associated with SSI than were radical procedures (mastectomy alone and mastectomy followed by immediate reconstruction) (P=0.0001).