Browsing by Author "Nussbaum, Daniel P"
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Item Open Access Comparing Survival After Resection, Ablation, and Radiation in Small Intrahepatic Cholangiocarcinoma.(Annals of surgical oncology, 2023-10) Masoud, Sabran J; Rhodin, Kristen E; Kanu, Elishama; Bao, Jiayin; Eckhoff, Austin M; Bartholomew, Alex J; Howell, Thomas C; Aykut, Berk; Kosovec, Juliann E; Palta, Manisha; Befera, Nicholas T; Kim, Charles Y; Herbert, Garth; Shah, Kevin N; Nussbaum, Daniel P; Blazer, Dan G; Zani, Sabino; Allen, Peter J; Lidsky, Michael EBackground
Hepatectomy is the cornerstone of curative-intent treatment for intrahepatic cholangiocarcinoma (ICC). However, in patients unable to be resected, data comparing efficacy of alternatives including thermal ablation and radiation therapy (RT) remain limited. Herein, we compared survival between resection and other liver-directed therapies for small ICC within a national cancer registry.Patients and methods
Patients with clinical stage I-III ICC < 3 cm diagnosed 2010-2018 who underwent resection, ablation, or RT were identified in the National Cancer Database. Overall survival (OS) was compared using Kaplan-Meier and multivariable Cox proportional hazards methods.Results
Of 545 patients, 297 (54.5%) underwent resection, 114 (20.9%) ablation, and 134 (24.6%) RT. Median OS was similar between resection and ablation [50.5 months, 95% confidence interval (CI) 37.5-73.9; 39.5 months, 95% CI 28.7-58.4, p = 0.14], both exceeding that of RT (20.9 months, 95% CI 14.1-28.3). RT patients had high rates of stage III disease (10.4% RT vs. 1.8% ablation vs. 11.8% resection, p < 0.001), but the lowest rates of chemotherapy utilization (9.0% RT vs. 15.8% ablation vs. 38.7% resection, p < 0.001). In multivariable analysis, resection and ablation were associated with reduced mortality compared with RT [hazard ratio (HR) 0.44, 95% CI 0.33-0.58 and HR 0.53, 95% CI 0.38-0.75, p < 0.001, respectively].Conclusion
Resection and ablation were associated with improved survival in patients with ICC < 3 cm compared with RT. Acknowledging confounders, anatomic constraints of ablation, limitations of available data, and need for prospective study, these results favor ablation in small ICC where resection is not feasible.Item Open Access Improving Outcomes in Colorectal Surgery by Sequential Implementation of Multiple Standardized Care Programs.(J Am Coll Surg, 2015-08) Keenan, Jeffrey E; Speicher, Paul J; Nussbaum, Daniel P; Adam, Mohamed Abdelgadir; Miller, Timothy E; Mantyh, Christopher R; Thacker, Julie KMBACKGROUND: The purpose of this study was to examine the impact of the sequential implementation of the enhanced recovery program (ERP) and surgical site infection bundle (SSIB) on short-term outcomes in colorectal surgery (CRS) to determine if the presence of multiple standardized care programs provides additive benefit. STUDY DESIGN: Institutional ACS-NSQIP data were used to identify patients who underwent elective CRS from September 2006 to March 2013. The cohort was stratified into 3 groups relative to implementation of the ERP (February 1, 2010) and SSIB (July 1, 2011). Unadjusted characteristics and 30-day outcomes were assessed, and inverse proportional weighting was then used to determine the adjusted effect of these programs. RESULTS: There were 787 patients included: 337, 165, and 285 in the pre-ERP/SSIB, post-ERP/pre-SSIB, and post-ERP/SSIB periods, respectively. After inverse probability weighting (IPW) adjustment, groups were balanced with respect to patient and procedural characteristics considered. Compared with the pre-ERP/SSIB group, the post-ERP/pre-SSIB group had significantly reduced length of hospitalization (8.3 vs 6.6 days, p = 0.01) but did not differ with respect to postoperative wound complications and sepsis. Subsequent introduction of the SSIB then resulted in a significant decrease in superficial SSI (16.1% vs 6.3%, p < 0.01) and postoperative sepsis (11.2% vs 1.8%, p < 0.01). Finally, inflation-adjusted mean hospital cost for a CRS admission fell from $31,926 in 2008 to $22,044 in 2013 (p < 0.01). CONCLUSIONS: Sequential implementation of the ERP and SSIB provided incremental improvements in CRS outcomes while controlling hospital costs, supporting their combined use as an effective strategy toward improving the quality of patient care.Item Open Access PIK3CA mutations enable targeting of a breast tumor dependency through mTOR-mediated MCL-1 translation.(Sci Transl Med, 2016-12-14) Anderson, Gray R; Wardell, Suzanne E; Cakir, Merve; Crawford, Lorin; Leeds, Jim C; Nussbaum, Daniel P; Shankar, Pallavi S; Soderquist, Ryan S; Stein, Elizabeth M; Tingley, Jennifer P; Winter, Peter S; Zieser-Misenheimer, Elizabeth K; Alley, Holly M; Yllanes, Alexander; Haney, Victoria; Blackwell, Kimberly L; McCall, Shannon J; McDonnell, Donald P; Wood, Kris CTherapies that efficiently induce apoptosis are likely to be required for durable clinical responses in patients with solid tumors. Using a pharmacological screening approach, we discovered that combined inhibition of B cell lymphoma-extra large (BCL-XL) and the mammalian target of rapamycin (mTOR)/4E-BP axis results in selective and synergistic induction of apoptosis in cellular and animal models of PIK3CA mutant breast cancers, including triple-negative tumors. Mechanistically, inhibition of mTOR/4E-BP suppresses myeloid cell leukemia-1 (MCL-1) protein translation only in PIK3CA mutant tumors, creating a synthetic dependence on BCL-XL This dual dependence on BCL-XL and MCL-1, but not on BCL-2, appears to be a fundamental property of diverse breast cancer cell lines, xenografts, and patient-derived tumors that is independent of the molecular subtype or PIK3CA mutational status. Furthermore, this dependence distinguishes breast cancers from normal breast epithelial cells, which are neither primed for apoptosis nor dependent on BCL-XL/MCL-1, suggesting a potential therapeutic window. By tilting the balance of pro- to antiapoptotic signals in the mitochondria, dual inhibition of MCL-1 and BCL-XL also sensitizes breast cancer cells to standard-of-care cytotoxic and targeted chemotherapies. Together, these results suggest that patients with PIK3CA mutant breast cancers may benefit from combined treatment with inhibitors of BCL-XL and the mTOR/4E-BP axis, whereas alternative methods of inhibiting MCL-1 and BCL-XL may be effective in tumors lacking PIK3CA mutations.