A medical oncologist’s approach to immunotherapy for advanced renal tumors: Is nephrectomy indicated?

Metastatic renal cell carcinoma is highly resistant to systemic therapy. Although interleukin-2 and interferon remain the most active agents for this disease, long-term survival rates remain poor. Two phase 3 trials, European Organization Research and Treatment of Cancer 30947 and Southwest Oncology Group 8949, have demonstrated a survival benefit of nephrectomy followed by interferon versus interferon alone in patients having an excellent performance status (PS 0 and 1). Removal of the primary tumor followed by interferon is not recommended for patients with a moderate or poor PS (PS 2–4). Even with this aggressive approach, most patients eventually will die from their kidney cancer; therefore, every patient with metastatic disease should be considered for enrollment into clinical trials.     

Gene expression profiling of renal medullary carcinoma: potential clinical relevance

BACKGROUND: Renal medullary carcinoma is a rare kidney tumor with highly aggressive behavior. This tumor occurs exclusively in young patients with sickle cell trait or disease. To the authors' knowledge, very little is known to date regarding the underlying molecular genetics of this tumor, and no effective therapy has been established. METHODS: The authors analyzed the gene expression profiles of 2 renal medullary carcinomas from patients with sickle cell trait using microarrays containing 21,632 cyclic DNA (cDNA) clones and compared them with the gene expression profiles of 64 renal tumors. RESULTS: Based on global gene clustering with 3583 selected cDNAs, the authors found a distinct molecular signature of renal medullary carcinoma, which clustered closely with urothelial (transitional cell) carcinoma of the renal pelvis, rather than renal cell carcinoma (RCC). This finding of a significant difference in the gene expression patterns of renal medullary carcinoma compared with RCC suggests that this tumor should not be treated as a conventional RCC but, rather, as a special malignancy. This study also identified genes/proteins that may serve as biomarkers for renal medullary carcinoma or as potential targets of novel therapies. In addition, comparative genomic microarray analysis allowed the authors to predict the lack of chromosomal imbalances in this tumor. CONCLUSIONS: To the authors' knowledge, the current study is the first molecular profiling of renal medullary carcinoma, a rare but highly aggressive kidney carcinoma. The genes that are expressed specifically in this tumor may lead to not only a better understanding of its molecular pathways and discoveries of novel diagnostic markers but also, more important, to effective therapeutic interventions.     

Comparison of Pain After Uterine Artery Embolization Using Tris-Acryl Gelatin Microspheres Versus Polyvinyl Alcohol Particles

When compared in a uterine artery embolization (UAE) animal model, Embospheres (ES) (Biosphere Medical, Rockland, MA) were found to induce less uterine ischemia than polyvinyl alcohol (PVA) particles. Given this finding, we aimed to test the hypothesis that ES is associated with less pain after UAE than PVA in human patients. We performed retrospective analysis on data from 72 consecutive UAE patients, collected from a prospectively acquired database. Patient-controlled analgesia (PCA) pump-delivered morphine sulfate (MS) dosages were compared between patients who received ES versus PVA. Subjective pain scores (SPS) were also compared between the two groups. Secondary outcome measures, including embolic volume and clinical outcome data, were also collected. Linear regression and t-test statistical analyses were performed. Null hypotheses were rejected at the p < 0.05 level. Mean follow-up period in the PVA population was 178 days (range 28–426), versus 96 days (range 24–197) in the ES population. The mean MS doses used by ES and PVA patients were 37.2 (s.d. 23.5) versus 47.1 (s.d. 26.8), respectively. This difference was not significant (p > 0.15). Utilizing a standard 0–10 pain scale, the mean peak SPS for the ES and PVA groups were 5.58 (s.d. 2.77) and 5.07 (s.d. 2.99), respectively. The difference was not significant. The mean amount of embolic material used in each ES and PVA patient was 4.86 cc (s.d. 3.01) and 3.52 cc (s.d. 1.63), respectively. The difference revealed a strong trend toward statistical significance (p = 0.05). There was one treatment failure in each group of patients. Within both patient samples, no significant correlation was found when comparing the volume of embolic used and subsequent MS dose. Despite a strong trend toward a significantly higher volume of ES used per patient, there is no subjective or objective difference in pain after UAE with ES when compared to PVA.     

Radiation doses in interventional radiology procedures: the RAD-IR study: part II: skin dose

PURPOSE: To determine peak skin dose (PSD), a measure of the likelihood of radiation-induced skin effects, for a variety of common interventional radiology and interventional neuroradiology procedures, and to identify procedures associated with a PSD greater than 2 Gy. MATERIALS AND METHODS: An observational study was conducted at seven academic medical centers in the United States. Sites prospectively contributed demographic and radiation dose data for subjects undergoing 21 specific procedures in a fluoroscopic suite equipped with built-in dosimetry capability. Comprehensive physics evaluations and periodic consistency checks were performed on each unit to verify the stability and consistency of the dosimeter. Seven of 12 fluoroscopic suites in the study were equipped with skin dose mapping software. RESULTS: Over a 3-year period, skin dose data were recorded for 800 instances of 21 interventional radiology procedures. Wide variation in PSD was observed for different instances of the same procedure. Some instances of each procedure we studied resulted in a PSD greater than 2 Gy, except for nephrostomy, pulmonary angiography, and inferior vena cava filter placement. Some instances of transjugular intrahepatic portosystemic shunt (TIPS) creation, renal/visceral angioplasty, and angiographic diagnosis and therapy of gastrointestinal hemorrhage produced PSDs greater than 3 Gy. Some instances of hepatic chemoembolization, other tumor embolization, and neuroembolization procedures in the head and spine produced PSDs greater than 5 Gy. In a subset of 709 instances of higher-dose procedures, there was good overall correlation between PSD and cumulative dose (r = 0.86; P <.000001) and between PSD and dose-area-product (r = 0.85, P <.000001), but there was wide variation in these relationships for individual instances. CONCLUSIONS: There are substantial variations in PSD among instances of the same procedure and among different procedure types. Most of the procedures observed may produce a PSD sufficient to cause deterministic effects in skin. It is suggested that dose data be recorded routinely for TIPS creation, angioplasty in the abdomen or pelvis, all embolization procedures, and especially for head and spine embolization procedures. Measurement or estimation of PSD is the best method for determining the likelihood of radiation-induced skin effects. Skin dose mapping is preferable to a single-point measurement of PSD.     

The impact of docetaxel, estramustine, and low dose hydrocortisone on the?quality of life of men with hormone refractory prostate cancer and their?partners: A feasibility study

Objectives:The quality of life (QoL) of 44 men with HRPC and 37 partners (primary caregivers, most residing with the patient) was assessed in a multicenter Phase II trial of docetaxel, estramustine and low dose hydrocortisone (CALGB 9780). A secondary objective was to test the feasibility of assessing partners QoL in a cooperative group setting. Patients and methods:Patients and partners were separately interviewed by telephone at baseline, two, four and six months by a single trained research interviewer. Patients QoL was measured by the FACT-P, Mental Health Inventory-17 (MHI-17), Brief Pain Inventory (BPI), a two-day log of pain medications, and the OARS for co-morbid conditions. Partners QoL was measured by the MHI-17, Caregiver Burden Interview, and co-morbid conditions. Results:The QoL study refusal rates were low for patients (4%) and partners (3%). Although patients tended to experience greater treatment side effects in the first two months (FACT Physical Well-Being item, P = 0.057), their cancer-specific emotions (e.g., worrying about worsening health) significantly improved at two and four months (FACT-Emotional Well-Being, P = 0.003, P = 0.03, respectively), as did their prostate cancer-specific physical problems (e.g., urination, pain), at two and four months (FACT-P, P = 0.001, P = 0.005, respectively). Partners anxiety significantly decreased over time (MHI,P < 0.05). Patients quality of life at two months was significantly related to their clinical response (FACT-P total and prostate cancer-specific problems, P < 0.05), and their clinical response was significantly related to a decrease in their partners anxiety at two months (MHI, P < 0.05). Conclusions:Despite feeling worse from side effects, patients prostate cancer-specific problems and emotional state significantly improved in the first four months of treatment. With treatment significantly affecting both patients and partners lives, and the successful assessment of partners QoL, QoL of both patients and partners could be used as important endpoints in selected clinical trials.     

Detection of carbamyl phosphate synthetase 1 deficiency using duodenal biopsy samples

The activity of urea cycle enzymes was assayed in duodenal biopsy specimens obtained from a female infant who presented with neonatal hyperammonaemia. All enzyme levels were normal except N-acetyl glutamate-dependent carbamyl phosphate synthetase 1 (CPS1) which was half the mean activity in normal control specimens. A similar deficiency of CPS1 was also shown in duodenal specimens from the patient's mother who became slightly symptomatic after relatively high protein meals and during pregnancy, and had spontaneously modified her diet to one with protein restriction. The patient is growing normally on a dietary regimen similar to that spontaneously adopted by her mother. Urea cycle enzyme activity in the duodenal biopsy material from the controls was similar to that found in the normal human liver and appears to have distinct advantages as a means of assaying for urea cycle defects in patients with hyperammonaemia and their relatives.     

Controlled trial of continuous inflating pressure for hyaline membrane disease

A controlled trial of elective intervention with continuous inflating pressure (CIP) was performed in infants with severe hyaline membrane disease who weighed more than 1000 g at birth. Infants entered the trial if their arterial oxygen tension (PaO2) fell below 60 mmHg while breathing a fractional inspired oxygen concentration (F1O2) greater than 0-95. 11 out of 12 infants in the CIP-treated group and 10 out of 12 in the control group survived. 7 treated and 6 control infants required mechanical ventilation. When CIP was started the Pao2 of the treated infants increased, and they breathed high concentrations of oxygen for a significantly shorter period than the control infants. During the 31-month duration of the trial 107 other infants with severe hyaline membrane disease were admitted who did not meet the criteria for entry to the trial. 37 survived after breathing high concentrations of oxygen (F1O2 greater than 0-60) spontaneously without any ventilatory assistance, and the remaining 70 infants were already being ventilated on their arrival in the unit, usually because they had required mechanical ventilation during transfer from other hospitals. The neonatal survival rate for those infants born in this hospital during the study period was 88% (50 out of 57 infants) and for those referred from other hospitals it was 69% (51 out of 74 infants). The maximum further increase in overall survival rate that might have been achieved in our population of infants if CIP had been initiated very early in the course of the illness was 5%--i.e. from 77% (101/131) to 82% (107/131).