Citations

What's known on the subject? and What does the study add? Postoperative complications for open radical nephrectomy ( ORN ), laparoscopic radical nephrectomy ( LRN ), and open partial nephrectomy ( OPN ) and its relationship with hospitalisation costs and mortality remain poorly described. The present population‐based study suggests modest differences in postoperative complications estimated at 27%, 23%, and 24% among patients with kidney cancer undergoing ORN , LRN , and OPN , respectively. Moreover, postoperative complications were associated with higher mortality, length of stay and total costs of hospitalisation. Objectives The association of complications after renal surgery for renal cell carcinoma ( RCC ) with in‐hospital mortality and costs remains to be defined. To describe the incidence of complications after open radical nephrectomy ( ORN ), laparoscopic RN ( LRN ), and open partial nephrectomy ( OPN ); and to evaluate its relationship with in‐hospital mortality and total costs. Patients and Methods We identified 49 983 individuals who underwent ORN (35 712), LRN (5327), or OPN (8944) for RCC at 2037 hospitals from the Nationwide Inpatient Sample 2001–2008. The outcomes assessed were in‐hospital mortality and total hospitalisation costs. Multivariable logistic regression and generalised estimating equations were used to test the associations between complications and in‐hospital mortality and total costs. Results With 26.0% of patients experiencing postoperative complications, there were modest differences in the proportion of patients with complications after ORN , LRN , and OPN at 27.0%, 22.6%, and 24.0%, respectively ( P < 0.001). After adjusting for patient and hospital variables, postoperative complications resulted in higher odds of in‐hospital death for ORN (odds ratio [ OR ] 7.20; P < 0.001), LRN ( OR 12.04; P < 0.001), and OPN ( OR 7.82; P < 0.001). Adjusted total costs also rose significantly with the presence of any postoperative complications compared with those without any complications for ORN ($21 242 vs $13 183; P < 0.001), LRN ($19 548 vs $12 555; P < 0.001), and OPN ($18 883 vs $12 098; P < 0.001). Conclusions With about a quarter of patients experiencing postoperative complications, adverse events for ORN , LRN , and OPN carry a significant risk of in‐hospital death and higher total costs. Efforts to reduce postoperative complications may correlate with substantial reductions in hospital mortality and total costs.

Abstract Background: Colorectal cancer (CRC) is the third most common incident cancer among women in the United States. Alcohol use has been proposed as a CRC risk factor, but existing observational data remain inconsistent. To date, relatively few studies have examined associations between alcohol use and CRC risk based on molecularly-defined subtypes. Aim: To evaluate associations between alcohol use and incident CRC overall, as well as by molecularly-defined subtypes including microsatellite instability (MSI), CpG island methylator phenotype (CIMP) and BRAF mutation status in the prospective, population-based, Iowa Women's Health Study (IWHS). Methods: The IWHS recruited 41,836 randomly selected Iowa women, ages 55–69 years at enrollment, in 1986. Women with prevalent cancers or no follow-up were excluded, leaving 38,001 eligible for this study. Alcohol use was obtained from a self-administered food frequency questionnaire at study baseline. Incident CRCs were identified through annual linkage with the State Health Registry of Iowa. Archived, paraffin-embedded tissue specimens were recently requested for incident CRC cases diagnosed through December 31, 2002. In the present study, useable tissue specimens were obtained and molecularly characterized for 563/1,255 cases (45%), whose baseline age, body mass index, physical activity level, total energy intake and alcohol use were similar to non-retrieved cases (p &gt; 0.05 for each comparison). Alcohol use was categorized as never (n=21,464), &lt; 3.4 g/day (n=8,313) and &gt; 3.4 g/day (n=8,224), based on the median split among users. Molecularly-defined CRC subtypes were categorized as MSI-high (MSIH; n=148), MSI-low or microsatellite stable (MSI-L/MSS; n=400); CIMP-positive (n=167) or CIMP-negative (n=368); and BRAF-mutation (n=154) or BRAF-wildtype (n=391). Relative risks (RRs) and 95% confidence intervals (95% CIs) were estimated for alcohol use compared to never drinkers, using multivariable Cox regression models adjusted for body mass index, waist-to-hip ratio, smoking status, physical activity level, exogenous estrogen use, and daily intakes of total energy, total fat, red meat, sucrose, calcium, folate, methionine and vitamin E. Results: There was no statistically significant association between alcohol use and overall CRC risk (RR=1.00; 95% CI = 0.86–1.15 for &lt; 3.4 g/day versus none; RR=1.06; 95% CI=0.91–1.24 for &gt;3.4 g/day versus none). Further, there were no associations with alcohol use for specific, molecularly-defined CRC subtypes (RRs shown for &gt; 3.4 g/day versus none): MSI-H (RR=1.07; 95% CI=0.70–1.64); MSI-L or MSS (RR=1.12; 95% CI=0.85–1.47); CIMP-positive (RR=0.97; 95% CI=0.64–1.47); CIMP-negative (RR=1.13; 95% CI=0.85–1.50); BRAF-mutation (RR=0.94; 95% CI=0.61–1.45); and BRAF-wildtype (RR=1.20; 95% CI=0.91–1.57). Conclusion: In this cohort of older women, alcohol use did not appear to be a risk factor for incident CRC, overall or by the defined molecular subtypes. Citation Information: Cancer Prev Res 2010;3(1 Suppl):A115.

Summary The importance of serum immunoglobulin (Ig)G concentration in IgG replacement therapy for primary immunodeficiency diseases is established in certain settings. Generally, IgG is infused via the intravenous (IVIG) or subcutaneous (SCIG) route. For IVIG infusion, published data demonstrate that higher IgG doses and trough levels provide patients with improved protection from infection. The same conclusions are not yet accepted for SCIG; data from two recent Phase III studies and a recent post-hoc analysis, however, suggest the same correlation between higher SCIG dose and serum IgG concentration and decreased incidence of infection seen with IVIG. Other measures of clinical efficacy have not been considered similarly. Thus, combined analyses of these and other published SCIG studies were performed; a full comparison of the 13 studies was, however, limited by non-standardized definitions and reporting. Despite these limitations, our analyses indicate that certain clinical outcomes improve at higher SCIG doses and associated higher serum IgG concentrations, and suggest that there might be opportunity to improve patient outcomes via SCIG dose adjustment.

Background: Compared with multiple daily injections (MDI), sensor-augmented pump (SAP) insulin therapy may reduce glycemic variability and oxidative stress in type 1 diabetes in a glycosylated hemoglobin (A1C)-independent manner. Subjects and Methods: The STAR 3 study compared SAP with MDI therapy for 1 year. Week-long continuous glucose monitoring studies were conducted at baseline and 1 year for assessment of glycemic variability in both groups. Soluble CD40 ligand (CD40L), a biomarker of inflammation and thrombocyte function, was measured at baseline and 1 year. Subjects were classified according to treatment group and 1-year A1C levels (<6.5%, 6.5–6.9%, 7–7.9%, ≥8%). Glycemic parameters were compared between SAP and MDI subjects in each A1C cohort. Results: At 1 year, sensor glucose values at A1C levels ≥6.5% were similar in the SAP and MDI groups. However, sensor glucose SD and coefficient of variation (CV) values were lower at A1C levels <8% among SAP than among MDI subjects; the overall between-group difference was significant for both SD ( P <0.01) and CV ( P =0.01). The overall mean amplitude of glycemic excursion was similar in MDI and SAP groups ( P =0.23). CD40L levels fell over the course of the study in both groups, but the between-group difference was not significant ( P =0.18). CD40L concentrations were unrelated to A1C, change in A1C from baseline, or glycemic variability. Conclusions: At comparable A1C levels of <8%, SAP reduced glycemic variability as measured by SD and CV compared with MDI. SAP may provide beneficial reductions in the number and severity of glycemic excursions.

Abstract Light-chain (AL) amyloidosis remains incurable despite recent therapeutic advances. Given the activity of the lenalidomide-alkylating agent combination in myeloma, we designed this phase 2 trial of lenalidomide, cyclophosphamide, and dexamethasone in AL amyloidosis. Thirty-five patients, including 24 previously untreated, were enrolled. Nearly one-half of the patients had cardiac stage III disease and 28% had ≥ 3 organs involved. The overall hematologic response (≥ partial response [PR]) rate was 60%, including 40% with very-good partial response or better. Using serum-free light chain for assessing response, 77% of patients had a hematologic response. Organ responses were seen in 29% of patients and were limited to those with a hematologic response. The median hematologic progression-free survival was 28.3 months, and the median overall survival was 37.8 months. Hematologic toxicity was the predominant adverse event, followed by fatigue, edema, and gastrointestinal symptoms. A grade 3 or higher toxicity occurred in 26 patients (74%) including ≥ grade 3 hematologic toxicity in 16 patients (46%) and ≥ grade 3 nonhematologic toxicity in 25 patients (71%). Seven patients (20%) died on study, primarily because of advanced disease. Lenalidomide, cyclophosphamide, and dexamethasone (CRd) is an effective combination for treatment of AL amyloidosis and leads to durable hematologic responses as well as organ responses with manageable toxicity. The trial was registered at www.clinicaltrials.gov (NCT00564889).

What's known on the subject? and What does the study add? There is great variability in the utilization of partial nephrectomy, but the causes of these variations are not well understood. The present study underscores the already observed phenomenon of surgical volume influencing surgical planning and outcomes, but it gets at why this might be so. We observe that high‐volume renal surgeons have different thresholds of ‘technical feasibility’. Objective To investigate why there continues to be wide variability in the application of partial nephrectomy ( PN ) for treating small renal masses despite guidelines in the US and E urope stating that a PN is a standard of care for a patient with a T 1 renal mass. Patients and Methods In June 2009, 764 surgeon‐members of the A merican U rologic A ssociation ( AUA ) participated in a survey evaluating the management of renal masses. Renal mass complexity was graded by nephrometry score ( NS ). Multivariable logistic regression models with generalized estimating equations were constructed to evaluate how tumour, surgeon and practice‐setting characteristics influence the use of PN . Results The survey response rate was 19%. Each urological surgeon responded to eight scenarios, providing 6112 evaluable cases. Tumour NS ranged from 4 to 10, and each unit increase in NS was associated with 59% increased likelihood of a surgeon offering RN on multivariable analysis (odds ratio [ OR ] = 1.59; 95% CI : 1.52–1.64). When holding patient and tumour characteristics constant, the following surgeon and practice‐setting characteristics significantly increased the odds of offering a PN: increasing renal case volume ( OR = 1.57; 95% CI : 1.27–1.95), academic practice ( OR = 1.80; 95% CI : 1.42–2.29), increasing PN % volume ( OR = 3.7; 95% CI : 2.46–5.55) and younger surgeon age (≤40 vs >50 years) ( OR = 1.64; 95% CI : 1.35–1.96). Conclusion The characteristics of a surgeon and the setting in which he or she practices influence the utilization of PN , the adherence to professional guidelines, and the threshold of tumour complexity at which a surgeon stops offering PN .