Citations

OBJECTIVE With improving medical therapies for chronic conditions, elderly patients increasingly present as candidates for operative intervention for degenerative diseases of the spine. To date, there is a paucity of studies examining complications in lumbar decompression, without fusion, that include patients older than 80 years. Using a multicenter national database, the authors of this study evaluated lumbar decompression in the elderly, including octogenarians, to evaluate for associations between age and patient outcomes. METHODS The 2011–2013 American College of Surgeons' National Surgical Quality Improvement Program data set was queried for patients 65 years and older with diagnosis and procedure codes inclusive of degenerative spine disease and lumbar decompression without fusion. Morbidity and mortality within the 30-day postoperative period were the primary outcomes. Secondary outcomes of interest included unplanned readmission within 30 days or discharge to a nonhome facility. Outcomes and operative characteristics were compared using chi-square tests, Kruskal-Wallis tests, and multivariable logistic regression models. RESULTS A total of 8744 patients were identified; of these patients 4573 (52.30%) were 65 years and older. Elderly patients were stratified into 3 age categories: 85 years or older (n = 314), 75–84 years (n = 1663), and 65–74 years (n = 2596). Univariate analysis showed that, compared with age younger than 65 years, increased age was associated with the number of levels (≥ 3), readmissions within 30 days, nonhome discharge, any complication, length of stay, and blood transfusion (all p < 0.001). On multivariable analysis and with younger than 65 years as the reference, increased age was associated with any minor complication (p < 0.001; ≥ 85 years: OR 3.47, 95% CI 1.69–7.13; 75–84 years: OR 2.34, 95% CI 1.45–3.78; and 65–74 years: OR 1.44, 95% CI 0.94–2.20), as well as discharge location other than home (p < 0.001; ≥ 85 years: OR 13.59, 95% CI 9.47–19.49; 75–84 years: OR 5.64, 95% CI 4.33–7.34; and 65–74 years: OR 2.61, 95% CI 2.05–3.32). CONCLUSIONS The authors' high-powered, multicenter analysis of lumbar decompression without fusion in the elderly, specifically including patients older than 80 years, demonstrates that increased age is associated with more extensive operations, resulting in longer hospital stays, increased rates of nonhome discharge, and minor complications.

BACKGROUND: Clinical trials demonstrate that postresection chemotherapy conveys survival benefit to patients with stage III colon cancer. It is unclear whether this benefit can be extrapolated to the elderly, who are underenrolled in clinical trials. OBJECTIVE: The purpose of this study was to determine outcomes of selected octogenarians with stage III colon cancer with/without postresection adjuvant therapy. DESIGN: This was a retrospective cohort study (2006–2011) using unadjusted Kaplan–Meier and adjusted Cox proportional hazards analyses of overall survival. SETTING: The study was conducted with the National Cancer Database. PATIENTS: We included patients 80 to 89 years of age who were undergoing curative-intent surgery for stage III colon cancer and excluded patients who received neoadjuvant therapy, died within 6 weeks of surgery, or had high comorbidity. MAIN OUTCOME MEASURES: Overall survival was the main measure. RESULTS: A total of 8141 octogenarians were included; 3483 (42.8%) received postresection chemotherapy, and 4658 (57.2%) underwent surgery alone. Patients receiving chemotherapy were younger (82.0 vs 84.0 years; p < 0.001), healthier (73.1% vs 70.4% with no comorbidities; p = 0.009), and more likely to have N2 disease (40.4% vs 32.8%; p < 0.001). Overall survival was improved in patients receiving adjuvant chemotherapy (median = 61.7 vs 35.0 months; p < 0.001). Subgroup analysis of patients offered chemotherapy but refusing (n = 1315) demonstrated overall survival worse than those receiving adjuvant chemotherapy (median = 42.7 vs 61.7 months; p < 0.001). Multivariable analysis adjusting for potential confounders showed therapy with surgery alone to be independently associated with increased mortality hazard (HR = 1.83; p < 0.001), and the mortality hazard remained elevated in patients who voluntarily refused adjuvant therapy (HR = 1.45; p < 0.001). LIMITATIONS: The study was limited by its retrospective, nonrandomized design. CONCLUSIONS: In selected octogenarians with stage III colon cancer, postresection adjuvant chemotherapy was associated with superior overall survival. However, less than half of the octogenarians with stage III colon cancer in the National Cancer Database received it. The remaining majority, who were all fit and survived ≥6 weeks postsurgery, could have derived benefit from adjuvant chemotherapy. This represents a substantial opportunity for quality improvement in treating octogenarians with stage III colon cancer.

Abstract Background: Surgical site infections (SSI) contribute to surgical patients' morbidity and costs. Operating room traffic may be a modifiable risk factor for SSI. We investigated the impact of additional operating room personnel on the risk of superficial SSI (sSSI). Patients and Methods: In this matched case-control study, cases included patients in whom sSSI developed in clean surgical incisions after elective, daytime operations. Control subjects were matched by age, gender, and procedure. Operating room personnel were classified as (1) surgical scrubbed, (2) surgical non-scrubbed, or (3) anesthesia. We used conditional logistic regression to test the extent to which additional personnel overall and from each work group were associated with infection. Results: In total, 474 patients and 803 control subjects were identified. Each additional person among total personnel and personnel from each work group was significantly associated with greater odds of infection (all personnel, odds ratio [OR] = 1.082, 95% confidence interval [CI] 1.031–1.134, p = 0.0013; surgical scrubbed OR = 1.132, 95% CI 1.029–1.245, p = 0.0105; surgical non-scrubbed OR = 1.123, 95% CI 1.008–1.251, p = 0.0357; anesthesia OR = 1.153, 95% CI 1.031–1.290, p = 0.0127). After adjusting for operative duration, body mass index, diabetes mellitus, and vascular disease, additional personnel and sSSI were no longer associated overall or for any work groups (total personnel OR = 1.033, 95% CI 0.974–1.095, p = 0.2746; surgical scrubbed OR = 1.060, 95% CI 0.952-1.179, p = 0.2893; surgical non-scrubbed OR = 1.023 95% CI 0.907–1.154, p = 0.7129; anesthesia OR = 1.051, 95% CI 0.926–1.193, p = 0.4442). Conclusion: The presence of additional operating room personnel was not independently associated with increased odds of sSSI. Efforts dedicated to sSSI reduction should focus on other modifiable risk factors.

Recent advances in follicular lymphoma (FL) have resulted in prolongation of overall survival (OS). Here we assessed if early events as defined by event‐free survival (EFS) at 12 and 24 months from diagnosis (EFS12/EFS24) can inform subsequent OS in FL. 920 newly diagnosed grade 1‐3A FL patients enrolled on the University of Iowa/Mayo Clinic Lymphoma SPORE Molecular Epidemiology Resource (MER) from 2002‐2012 were initially evaluated. EFS was defined as time from diagnosis to progression, relapse, re‐treatment, or death due to any cause. OS was compared to age‐and‐sex‐matched survival in the general US population using standardized mortality ratios (SMR) and 95% confidence intervals (CI). We used a cohort of 412 FL patients from two Lyon, France hospital registries for independent replication. Patients who failed to achieve EFS12 had poor subsequent OS (MER SMR = 3.72, 95%CI: 2.78‐4.88; Lyon SMR = 8.74, 95%CI: 5.41‐13.36). Conversely, patients achieving EFS12 had no added mortality beyond the background population (MER SMR = 0.73, 95%CI: 0.56‐0.94, Lyon SMR = 1.02, 95%CI: 0.58‐1.65). Patients with early events after immunochemotherapy had especially poor outcomes (EFS12 failure: MER SMR = 17.63, 95%CI:11.97‐25.02, Lyon SMR = 19.10, 95%CI:9.86‐33.36; EFS24 failure: MER SMR = 13.02, 95%CI:9.31‐17.74, Lyon SMR = 7.22, 95%CI:4.13‐11.74). In a combined dataset of all patients from both cohorts, baseline FLIPI was no longer informative in EFS12 achievers. Reassessment of patient status at 12 months from diagnosis in follicular lymphoma patients, or at 24 months in patients treated with immunochemotherapy, is a strong predictor of subsequent overall survival in FL. Early event status provides a simple, clinically relevant endpoint for studies assessing outcome in FL. Am. J. Hematol. 91:1096–1101, 2016. © 2016 Wiley Periodicals, Inc.

Abstract Background. DLBCL is the most common non-Hodgkin lymphoma (NHL) subtype in western countries and is known to be clinically heterogeneous. Gene expression profiling has identified two major, biologically distinctive DLBCL subtypes on the basis of their cell-of-origin (COO): the germinal center B-cell (GCB) - characterized by BCL2 rearrangement and C-REL amplification, and activated B-cell (ABC) - characterized by constitutive activation of the NF-kB pathway. Recently, the InterLymph Subtypes Project identified medical history, lifestyle, and family history risk factors for DLBCL using a large pooled analysis of case-control studies. In this study we evaluated these same risk factors for etiologic heterogeneity as defined by DLBCL COO. Methods. For this analysis we used a clinic-based study of newly diagnosed NHL cases and frequency matched controls, enrolled from 2002-2012, with 474 DLBCL cases and 2203 controls. COO was determined clinically using the Hans algorithm, which is based on immunohistochemistry markers using formalin-fixed, paraffin-embedded tumor tissue. Amongst DLBCL cases 107 were ABC, 207 were GCB, and 160 were missing subtype (tissue unavailable). Risk factor data, including body mass index (BMI), smoking, alcohol use, any allergy, asthma, blood transfusion, diabetes, rheumatoid arthritis, sun exposure, lived on a farm and family history of hematologic malignancy, were collected from self-administered questionnaires. Polytomous logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals for ABC and GCB subtypes, adjusted for age and sex. Results. The mean age of cases was 60.4 years with 53% male; the mean age of controls was 61.6 years and 53% male. We identified a strong positive association for BMI with risk of ABC but not GBC DLBCL (p-heterogeneity 0.025). Compared to BMI 18.5-24.9 kg/m2, those with a BMI of 25.0-29.9 (OR = 1.65; 0.93-2.93) or 30+ (OR = 2.61; 1.48-4.62) were at increased risk of ABC DLBCL. There was no association for a BMI of 25.0-29.9 (OR = 0.91; 0.63-1.31) or 30+ (OR = 1.21; 0.83-1.76) with GCB DLBCL. There was no evidence of significant heterogeneity between ABC and GCB DLBCL for the other risk factors that we evaluated. Further adjustment of the BMI association for educational level, smoking, and alcohol only slightly attenuated these findings. Conclusions. We observed a strong positive association of BMI with ABC but not GCB DLBCL. In contrast, other evaluated risk factors showed no heterogeneity by COO. While BMI has not been clearly associated with NHL overall, there has been evidence for an association with DLBCL. The etiologic heterogeneity we observed for ABC DLBCL is notable as BMI is also a strong risk factor for multiple myeloma, another post-germinal center B-cell malignancy. While requiring replication, our findings suggest BMI may influence B-cell neoplasia through effect on post-germinal center pathways. Citation Format: Matthew K. Breitenstein, Megan M. O’Byrne, Andrew L. Feldman, Carrie A. Thompson, William R. Macon, Grzegorz S. Nowakowski, Stephen M. Ansell, Susan L. Slager, Thomas M. Habermann, James R. Cerhan. Body mass index shows etiologic heterogeneity for risk of diffuse large B-cell lymphoma (DLBCL) subtype defined by cell-of-origin. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1762.

BACKGROUNDIn an ECOG‐ACRIN Cancer Research Group study (E1496), maintenance rituximab (MR) was reported to prolong progression‐free survival (PFS) in comparison with observation (OBS) alone in patients with indolent lymphoma after induction chemotherapy. Here the long‐term follow‐up of the same patient cohort is presented.METHODSPatients with indolent lymphoma received induction chemotherapy with cyclophosphamide, vincristine, and prednisone (CVP). Patients with stable disease or a better response were then randomized to weekly rituximab (375 mg/m2 × 4 doses) every 6 months for 2 years (MR) or to OBS. The primary endpoint was PFS; the secondary endpoints were overall survival (OS), response rate, and toxicities.RESULTSOf the 387 patients who initially received CVP induction, 158 were randomized to MR, and 153 were randomized to OBS. After a median follow‐up of 11.5 years, patients on MR had longer median PFS (4.8 years) than patients on OBS (1.3 years; hazard ratio [HR], 0.49; P < .0001). However, there was no difference in OS between MR and OBS (10‐year OS, 67% vs 59%; median OS, 13.5 years vs not reached; HR, 0.91; P = .69). Other than MR, only minimal residual disease after induction therapy was significantly associated with PFS on multivariate analysis (HR, 0.71; P = .02). A low initial tumor burden, minimal residual disease, follicular histology, a low Follicular Lymphoma International Prognostic Index score, and female sex were associated with longer OS. There was no increase in the rate of second primary malignancies with MR vs OBS.CONCLUSIONSWith long‐term follow‐up, MR did not influence OS. The PFS benefit was maintained. MR should be considered optional for patients with indolent B‐cell lymphoma. Cancer 2016;122:2996‐3004. © 2016 American Cancer Society.

AbstractSingle nucleotide polymorphisms (SNPs) in FCγ‐receptor genes FCGR3A (rs396991) and FCGR2A (rs1801274) influence the affinity of the Fc portion of anti‐CD20 immunoglobulin G1 monoclonal antibody. Their roles in diffuse large B‐cell lymphoma (DLBCL) treated with rituximab in combination with anthracycline‐based chemotherapy remain controversial. To address this question, we genotyped FCGR2A and FCGR3A SNPs in two prospective DLBCL cohorts from Lymphoma Study Association trials (N = 554) and Iowa/Mayo Specialized Program Of Research Excellence (N = 580). Correlations with treatment response and hematological toxicity were assessed in Lymphoma Study Association. Correlation with event‐free survival (EFS) and overall survival (OS) was performed in both cohorts, followed by a meta‐analysis to increase power. Our study shows the absence of correlation between these SNPs and treatment response. Grades 3 and 4 febrile neutropenia during treatment was more frequently observed in FCGR3A VV (39%) than VF (29%) and FF (32%) carriers (p = 0.04). Our analysis for EFS and OS shows that FCGR3A was not associated with outcome. In a meta‐analysis using an ordinal model, FCGR2A (per R allele) was associated with a better EFS (hazard ratio = 0.87; 95%CI, 0.76–0.99; p = 0.04) and OS (hazard ratio = 0.86; 95%CI, 0.73–1.00; p = 0.05) which was not altered after adjustment for the International Prognostic Index. Overall, our data demonstrate that patients with DLBCL with the low‐affinity FCγRIIA RR had an unexpectedly better outcome than FCγRIIA H carriers. Whether rituximab efficacy is improved in FCγRIIA RR patients due a clearance reduction or other functions of FCγRIIA in DLBCL should be investigated (clinicaltrials.gov identifiers: NCT00135499, NTC00135499 NCT00140595, NCT00144807, NCT00144755, NCT01087424, and NCT00301821). Copyright © 2016 John Wiley & Sons, Ltd.