Citations

Operating room (OR) scheduling is an important operational problem for most hospitals. In this study, we present a novel two-stage stochastic mixed-integer programming model to minimize total expected operating cost given that scheduling decisions are made before the resolution of uncertainty in surgery durations. We use this model to quantify the benefit of pooling ORs as a shared resource and to illustrate the impact of parallel surgery processing on surgery schedules. Decisions in our model include the number of ORs to open each day, the allocation of surgeries to ORs, the sequence of surgeries within each OR, and the start time for each surgeon. Realistic-sized instances of our model are difficult or impossible to solve with standard stochastic programming techniques. Therefore, we exploit several structural properties of the model to achieve computational advantages. Furthermore, we describe a novel set of widely applicable valid inequalities that make it possible to solve practical instances. Based on our results for different resource usage schemes, we conclude that the impact of parallel surgery processing and the benefit of OR pooling are significant. The latter may lead to total cost reductions between 21% and 59% on average.

Breast cancer is the most common type of cancer diagnosed in women. Anthracyclines and taxanes are the most active and widely used chemotherapeutic agents in the treatment of both early-stage and advanced breast cancer. In the past decade, novel formulations of these cytotoxic agents have been developed to improve efficacy and decrease toxicity. nab-paclitaxel is a solvent-free, albumin-bound 130-nm particle form of paclitaxel (Abraxane®, Abraxis Bioscience, CA, USA), which was developed to avoid toxicities associated with the Cremophor vehicle used in solvent-based paclitaxel. In a Phase III study, nab-paclitaxel demonstrated higher response rates, a better safety profile compared with conventional paclitaxel, and improved survival in patients receiving it as second-line therapy. Based on this pivotal trial, nab-paclitaxel is now approved in the USA for treatment of breast cancer after failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant therapy where prior therapy included an anthracycline unless clinically contraindicated. Recently, several Phase II studies have suggested a role for nab-paclitaxel as a single agent and in combination with other agents for first-line treatment of metastatic breast cancer. Studies are ongoing to explore the use of nab-paclitaxel in other solid tumors such as non-small-cell lung cancer, ovarian cancer and malignant melanoma.

Abstract The canonical Wnt signaling pathway is pathogenic in a variety of cancers. We previously identified aberrant expression of the Wnt pathway transcription factor and target gene lymphoid enhancer binding factor-1 (LEF1) in chronic lymphocytic leukemia (CLL). This suggested that the Wnt signaling pathway has a role in the biology of CLL. In this study, we performed a Wnt pathway analysis using gene expression profiling and identified aberrant regulation of Wnt pathway target genes, ligands, and signaling members in CLL cells. Furthermore, we identified aberrant protein expression of LEF-1 specifically in CLL but not in normal mature B-cell subsets or after B-cell activation. Using the T cell–specific transcription factor/LEF (TCF/LEF) dual luciferase reporter assay, we demonstrated constitutive Wnt pathway activation in CLL, although the pathway was inactive in normal peripheral B cells. Importantly, LEF-1 knockdown decreased CLL B-cell survival. We also identified LEF-1 expression in CD19+/CD5+ cells obtained from patients with monoclonal B-cell lymphocytosis, suggesting a role for LEF-1 early in CLL leukemogenesis. This study has identified the constitutive activation and prosurvival function of LEF-1 and the Wnt pathway in CLL and uncovered a possible role for these factors in the preleukemic state of monoclonal B-cell lymphocytosis.

Background Osteochondritis dissecans lesions of the knee in adult patients frequently require surgical intervention. However, the ideal method of osteochondral fragment fixation remains uncertain. Purpose This study was undertaken to determine the clinical, functional, and radiographic outcomes of bioabsorbable fixation for unstable osteochondritis dissecans lesions involving the femoral condyles of the knee in skeletally mature patients. Study Design Case series; Level of evidence, 4. Methods Skeletally mature patients with an unstable osteochondritis dissecans lesion of the femoral condyle (Ewing and Voto stages II-IV) treated with bioabsorbable internal fixation and minimum 1-year follow-up were included in this retrospective study cohort. Pre- and postoperative radiographs were reviewed and postoperative Lysholm and International Knee Documentation Committee (IKDC) scores were documented. Results A total of 21 knees in 21 patients satisfied the inclusion criteria, and 3 patients were lost to follow-up. The remaining 18 patients were evaluated at a mean of 59 months after surgery (range, 12-154 months). The 14 male and 4 female patients had a mean age of 19 years at the time of surgery (range, 14-39 years). Ewing and Voto classification included 8 stage II lesions, 9 stage III lesions, and 1 stage IV lesion. Fragment fixation methods included bioabsorbable nails (11), pins (3), darts (2), screws (1), and combined screws and darts (1). Mean postoperative Lysholm and IKDC scores were 85 and 82, respectively. Fragment union occurred in 12 knees (67%); the remaining 6 knees (33%) required removal of the loose fragment. Of the 11 patients treated with bioabsorbable nails, 2 (18%) required reoperation for nail back-out. Conclusion The authors recommend caution when using bioabsorbable fixation for osteochondritis dissecans lesions in skeletally mature patients because of the low rate of clinical healing and high complication rate. Failure with unthreaded fixation devices may be caused by inadequate compression and not necessarily be related to bioabsorbability.

Background A major challenge for randomized phase III oncology trials is the frequent low rates of patient enrollment, resulting in high rates of premature closure due to insufficient accrual. Purpose We conducted a pilot study to determine the extent of trial closure due to poor accrual, feasibility of identifying trial factors associated with sufficient accrual, impact of redesign strategies on trial accrual, and accrual benchmarks designating high failure risk in the clinical trials cooperative group (CTCG) setting. Methods A subset of phase III trials opened by five CTCGs between August 1991 and March 2004 was evaluated. Design elements, experimental agents, redesign strategies, and pretrial accrual assessment supporting accrual predictions were abstracted from CTCG documents. Percent actual/predicted accrual rate averaged per month was calculated. Trials were categorized as having sufficient or insufficient accrual based on reason for trial termination. Analyses included univariate and bivariate summaries to identify potential trial factors associated with accrual sufficiency. Results Among 40 trials from one CTCG, 21 (52.5%) trials closed due to insufficient accrual. In 82 trials from five CTCGs, therapeutic trials accrued sufficiently more often than nontherapeutic trials (59% vs 27%, p = 0.05). Trials including pretrial accrual assessment more often achieved sufficient accrual than those without (67% vs 47%, p = 0.08). Fewer exclusion criteria, shorter consent forms, other CTCG participation, and trial design simplicity were not associated with achieving sufficient accrual. Trials accruing at a rate much lower than predicted (<35% actual/predicted accrual rate) were consistently closed due to insufficient accrual. Limitations This trial subset under-represents certain experimental modalities. Data sources do not allow accounting for all factors potentially related to accrual success. Conclusion Trial closure due to insufficient accrual is common. Certain trial design factors appear associated with attaining sufficient accrual. Defining accrual benchmarks for early trial termination or redesign is feasible, but better accrual prediction methods are critically needed. Future studies should focus on identifying trial factors that allow more accurate accrual predictions and strategies that can salvage open trials experiencing slow accrual. Clinical Trials 2010; 7: 312—321. http://ctj.sagepub.com

With continued growth of the elderly population and improvements in cancer therapies, the number of patients with symptomatic spinal metastases is likely to increase, and this is a condition that commonly leads to debilitating neurological dysfunction and pain. Advancements in surgical techniques of resection and spinal reconstruction, improvements in clinical outcomes following various treatment modalities, generally increased overall survival in patients with metastatic spine disease, and a recent randomized trial by Patchell and colleagues demonstrating the superiority of a combined surgical/radiotherapeutic approach over a radiotherapy-only strategy have led many to suggest increasingly aggressive interventions for patients with such lesions. Optimal management of spinal metastases encompasses numerous medical specialties, including neurosurgery, orthopedic surgery, medical and radiation oncology, radiology, and rehabilitation medicine. In this review, the clinical presentation, diagnosis, and management of spinal metastatic disease are discussed. Ultimately, the goal of treatment in patients with spinal metastases remains palliative, and clinical judgment is required to select the appropriate patients for surgical intervention.