Sclerotic osseous metastases from renal cell carcinoma

This case series describes and illustrates three cases of sclerotic osseous metastases from untreated renal cell carcinoma (RCC). RCC is commonly metastatic to the skeleton but almost always produces lytic metastases, with only three prior reports of sclerotic metastases identified in the literature. Sclerotic metastasis causing low back pain was the initial disease presentation in two of the three patients in this case series and the first manifestation of metastatic disease in one. The most common metastatic sites of RCC, i.e., retroperitoneal lymph nodes, lung, and liver, were not identified in any of the cases, and skeletal involvement with epidural extension was the only site of metastasis in two. Pathologic specimens from all three cases revealed RCC of high nuclear grade.     

Early postoperative jejunostomy feeding with an immune modulating diet in patients undergoing resectional surgery for upper gastrointestinal cancer: a prospective, randomized, controlled, double-blind study

BACKGROUND: The provision of perioperative immune modulating enteral feeds after major surgery may result in reduced infective complications, but meta-analyses have not demonstrated a survival advantage. The aim of this study was to determine whether early postoperative immune modulating jejunostomy feeding results in reduced infective complications in patients undergoing resectional surgery for upper gastrointestinal cancer. METHODS: A total of 120 patients undergoing resection for cancers of the pancreas, oesophagus and stomach were randomized in a double-blind manner to receive jejunostomy feeding with an immune modulating diet (Stresson-Group A) or an isonitrogenous, isocaloric feed (1250 Calories and 75 g protein/l--Nutrison High Protein-Group B) for 10-15 days. Feeding was commenced 4h postoperatively and continued for 20 h/day. The target volume (ml/h) was 25 on day 0, 50 on day 1, and 75 thereafter. Outcome measures included complications, hospital stay and mortality. RESULTS: A total of 108 patients (54 in each group) were analysed. Feed delivery, although less than targeted, was similar in both groups. There were 6 (11%) deaths in each group. Median (IQR) postoperative hospital stay was 14.5 (12-23) days in Group A and 17.5 (13-23) days in Group B (P=0.48). A total of 24 (44%) patients in each group had infective complications (P=1.0). A total of 21 (39%) patients in Group A and 28 (52%) in Group B had non-infective complications (P=0.18). Jejunostomy-related complications occurred in 26 (48%) patients in Group A and 30 (56%) in Group B (P=0.3). CONCLUSION: Early postoperative feeding with an immune modulating diet conferred no outcome advantage when compared with a standard feed.     

Analysis of a tubular haemodialyser—effect of ultrafiltration and dialysate concentration

A theoretical analysis has been made of mass transfer in a hollow-fibre artificial kidney with ultrafiltration for: (i) a constant dialysate concentration and (ii) a variable dialysate concentration along the tube length. The latter is a conjugated boundary-value problem. The solution is obtained by the method of separation of variables using an infinite series expansion considering the fluid to be dilute and Newtonian. Results indicate that the ultrafiltration rate, permeability of the membrane and the nonzero dialysate concentration all have a significant effect on the clearance of the solute. The tubular diameter and length have very little effect on the clearance of the solute for a constant membrane surface area, ultrafiltration rate and a low membrane permeability. At high ultrafiltration rates, the effect of the solute concentration in the dialysate phase on the clearance become negligible. This analysis is compared with those of Popovich et al. (1971), Ross (1974) and Cooneyet al. (1974).     

Comparison of four early posttherapy imaging changes (EPTIC; RECIST 1.0, tumor shrinkage, computed tomography tumor density, Choi criteria) in assessing outcome to vascular endothelial growth factor-targeted therapy in patients with advanced renal cell carcinoma

Background

Vascular endothelial growth factor (VEGF)-targeted therapy has become standard treatment for patients with metastatic renal cell cancer (mRCC). Since these therapies can induce tumor necrosis and minimal tumor shrinkage, Response Evaluation Criteria in Solid Tumors (RECIST) may not be optimal for predicting clinical outcome.

Objective

To systematically determine the optimal early posttherapy imaging changes (EPTIC) to separate responders and nonresponders at the first posttreatment follow-up computed tomography (CT).

Design, setting, and participants

Seventy mRCC patients with 155 target lesions treated with first-line sunitinib, sorafenib, or bevacizumab at academic medical centers underwent contrast-enhanced thoracic and abdominal CT at baseline and first follow-up after therapy initiation (median: 78 d after therapy initiation; range: 31–223 d).

Measurements

Evaluations were performed according to (1) RECIST 1.0; (2) Choi criteria; (3) tumor shrinkage (TS) of ≥10% decrease in sum of the longest unidimensional diameter (SLD); and (4) 15% or 20% decrease in mean CT tumor density. Correlation with time to treatment failure (TTF) and overall survival (OS) were compared and stratified by response to each of the radiologic criteria.

Results and limitations

Eleven patients were considered responders by RECIST 1.0; 49 based on Choi criteria; 31 patients had ≥10% decrease in the SLD; and 36 and 32 patients had ≥15% and ≥20% decrease, respectively, in mean tumor density on CT. Only the threshold of 10% decrease in the SLD was statistically significant in predicting TTF (10.4 vs 5.1 mo; p = 0.02) and OS (32.5 vs 15.8 mo; p = 0.002). Receiver operating characteristic analysis yielded a 10% decrease in SLD as the optimal size change threshold for responders. The retrospective nature of the study and measurements by a single oncoradiologist are inherent limitations.

Conclusions

In the retrospectively analyzed study population of mRCC patients receiving VEGF-targeted agents, a 10% reduction in the SLD on the first follow-up CT was an optimal early predictor of outcome.     

Limitations in knowledge of HIV transmission among HIV-positive patients accessing case management services in a resource-poor setting

HIV has increasingly become an infection of poverty. Adequate HIV transmission knowledge among HIV-positive patients is necessary to reduce the risk of secondary infection and protect those who are uninfected from transmission. This study was conducted among individuals enrolled in a program that serves impoverished HIV patients in the Boston area. Although the mean HIV transmission knowledge score was 80% for this group, a significant proportion of patients demonstrated limitations in knowledge of HIV transmission. Highly vulnerable patients, such as those who reported not accessing HIV medications, a history of sexual abuse, or problems getting clothing, had lower levels of HIV knowledge. This paper hopes to alert providers that their most vulnerable patients may be at an increased risk of re-infection or transmission due to limited HIV knowledge. Programs that serve HIV-positive patients coping with poverty and other serious problems need to ensure adequate knowledge of HIV transmission to reduce the overall burden of HIV in resource-poor settings.     

Physiogenomic Analysis of Localized fMRI Brain Activity in Schizophrenia

The search for genetic factors associated with disease is complicated by the complexity of the biological pathways linking genotype and phenotype. This analytical complexity is particularly concerning in diseases historically lacking reliable diagnostic biological markers, such as schizophrenia and other mental disorders. We investigate the use of functional magnetic resonance imaging (fMRI) as an intermediate phenotype (endophenotype) to identify physiogenomic associations to schizophrenia. We screened 99 subjects, 30 subjects diagnosed with schizophrenia, 13 unaffected relatives of schizophrenia patients, and 56 unrelated controls, for gene polymorphisms associated with fMRI activation patterns at two locations in temporal and frontal lobes previously implied in schizophrenia. A total of 22 single nucleotide polymorphisms (SNPs) in 15 genes from the dopamine and serotonin neurotransmission pathways were genotyped in all subjects. We identified three SNPs in genes that are significantly associated with fMRI activity. SNPs of the dopamine beta-hydroxylase (DBH) gene and of the dopamine receptor D4 (DRD4) were associated with activity in the temporal and frontal lobes, respectively. One SNP of serotonin-3A receptor (HTR3A) was associated with temporal lobe activity. The results of this study support the physiogenomic analysis of neuroimaging data to discover associations between genotype and disease-related phenotypes.     

High fat diet affects reproductive functions in female diet-induced obese and dietary resistant rats

The incidence of ovulatory disorders is common in obese animal models. The mechanism behind this effect is unclear. We hypothesised that a high-fat (HF) diet induces alterations in neuroendocrine mechanisms resulting in anovulation in diet-induced obese (DIO) animals. Adult female DIO and diet-resistant (DR) rats were fed either chow or a HF diet (45% calories from fat) for 6 weeks. Oestrous cyclicity and body weight were monitored regularly. At the end of treatment, rats were implanted with a jugular catheter to monitor luteinising hormone (LH) levels on the day of pro-oestrous. Rats were sacrificed on the next pro-oestrous, and their brains and ovaries were collected. Plasma from trunk blood was analysed for oestradiol and leptin concentrations. Ovaries were fixed and sectioned for histological analysis. Brains were removed, frozen and sectioned, and norepinephrine (NE) concentrations in discrete hypothalamic areas were measured using high-performance liquid chromatography with electrochemical detection. A HF diet exposure affected oestrous cyclicity in both DIO and DR rats, with the effect being more pronounced in DIO animals. HF diet exposure increased leptin levels in both DIO and DR rats. Oestradiol levels were low in the DIO-HF group. NE levels in the hypothalamus were unaffected by HF diet or genotype. A normal LH surge was observed in DR-Chow rats and LH levels were low in the remaining groups. These results lead to the conclusion that DIO rats have an inherently reduced reproductive capacity and exposure to a HF diet decreases it further. A reduction in oestradiol and LH surge levels could contribute to this effect; however, the underlying mechanisms need to be investigated further.