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Fabian M. Johnston, Michael N. Mavros, Joseph M. Herman and Timothy M. Pawlik

The liver is one of the most common sites for metastatic disease, and optimal management of hepatic metastases often requires a multidisciplinary approach. Most commonly, liver metastases are derived from a colorectal or neuroendocrine primary tumor. Liver resection with curative intent is standard for resectable cases, but unfortunately most patients are not initially resectable because of the size, location, and/or extent of disease; inadequate remnant liver volume; or comorbidities. For patients with liver-limited or liver-dominant colorectal liver metastases (CRLM), the current challenges are to use different locoregional treatments to convert some borderline unresectable cases to resectable, and improve local control and overall survival. Although neuroendocrine liver metastases (NELM) may behave in a relatively indolent manner from an oncologic perspective, significant morbidity may be caused by excess hormone production when compared with metastatic liver disease from other primaries, and liver-directed treatment may be beneficial in reducing symptoms and perhaps extending survival. In the multidisciplinary management of patients with liver metastases, local therapies are especially important. Local approaches may be complementary (ie, portal vein embolization) or an alternative (ie, ablation, hepatic arterial infusion, selective radioembolization, and stereotactic body radiotherapy) to surgical resection. This article evaluates the available evidence on current regional strategies for managing patients with liver metastases, with an emphasis on CRLM and NELM, highlighting the clinical usefulness and limitations of each modality.

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Jordan M. Cloyd, Chengli Shen, Heena Santry, John Bridges, Mary Dillhoff, Aslam Ejaz, Timothy M. Pawlik and Allan Tsung

Background: Current guidelines support either immediate surgical resection or neoadjuvant therapy (NT) for patients with resectable pancreatic ductal adenocarcinoma (PDAC). However, which patients are selected for NT and whether disparities exist in the use of NT for PDAC are not well understood. Methods: Using the National Cancer Database from 2004 through 2016, the clinical, demographic, socioeconomic, and hospital-related characteristics of patients with stage I/II PDAC who underwent immediate surgery versus NT followed by surgery were compared. Results: Among 58,124 patients who underwent pancreatectomy, 8,124 (14.0%) received NT whereas 50,000 (86.0%) did not. Use of NT increased significantly throughout the study period (from 3.5% in 2004 to 26.4% in 2016). Multivariable logistic regression analysis showed that travel distance, education level, hospital facility type, clinical T stage, tumor size, and year of diagnosis were associated with increased use of NT, whereas comorbidities, uninsured/Medicaid status, South/West geography, left-sided tumor location, and increasing age were associated with immediate surgery (all P<.001). Based on logistic regression–derived interaction factors, the association between NT use and median income, education level, Midwest location, clinical T stage, and clinical N stage significantly increased over time (all P<.01). Conclusions: In addition to traditional clinicopathologic factors, several demographic, socioeconomic, and hospital-related factors are associated with use of NT for PDAC. Because NT is used increasingly for PDAC, efforts to reduce disparities will be critical in improving outcomes for all patients with pancreatic cancer.

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Katherine Y. Fan, Avani S. Dholakia, Aaron T. Wild, Zheng Su, Amy Hacker-Prietz, Rachit Kumar, Mary Hodgin, Charles C. Hsu, Dung T. Le, Ana De Jesus-Acosta, Luis A. Diaz Jr, Daniel A. Laheru, Ralph H. Hruban, Elliot K. Fishman, Todd D. Brown, Timothy M. Pawlik, Christopher L. Wolfgang, Phuoc T. Tran and Joseph M. Herman

An association between diabetes mellitus and pancreatic ductal adenocarcinoma (PDA) has long been recognized. This article assesses the effect of the baseline hemoglobin-A1c (HbA1c) value on the clinical outcomes of patients with PDA. HbA1c values were prospectively collected on 656 consecutive patients presenting to a pancreas multidisciplinary cancer clinic from 2009 to 2012. Patients were diagnosed with benign pancreatic disease (BPD) or biopsy-confirmed resectable (R), borderline/locally advanced (BL), or metastatic (M) PDA. Excluded were those with prior treatment for PDA or a history of chronic diabetes mellitus (>1-year or unknown duration), resulting in a final cohort of 284 patients. Of 284 patients, 44 had benign disease, 62 had R-PDA, 115 had BL-PDA, and 63 had M-PDA. Patients with malignant disease (R-, BL-, and M-PDA) collectively had a higher average HbA1c value than patients with BPD (6.1% vs 5.6%; P<.001). Among patients with PDA (n=240), HbA1c values of 6.5% or greater were significantly associated with inferior overall survival (OS) compared with patients with HbA1c values less than 6.5% (hazard ratio [HR], 1.74; OS, 10.2 vs 13.0 months; P=.007), along with other known prognostic factors, such as age of 65 years or older, ECOG performance status of 1 or greater, carbohydrate antigen 19-9 level greater than 90, tumor size larger than 3 cm, and disease stage. HbA1c values of 6.5% or greater remained in the final predictive model using backward elimination (HR, 1.46; P=.097), indicating that HbA1c values of 6.5% or greater influence OS of patients with PDA even when accounting for other known prognostic factors. HbA1c level at presentation is significantly higher in patients with PDA than patients with BPD and seems to affect survival.

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Al B. Benson III, Michael I. D’Angelica, Thomas A. Abrams, Chandrakanth Are, P. Mark Bloomston, Daniel T. Chang, Bryan M. Clary, Anne M. Covey, William D. Ensminger, Renuka Iyer, R. Kate Kelley, David Linehan, Mokenge P. Malafa, Steven G. Meranze, James O. Park, Timothy Pawlik, James A. Posey, Courtney Scaife, Tracey Schefter, Elin R. Sigurdson, G. Gary Tian, Jean-Nicolas Vauthey, Alan P. Venook, Yun Yen, Andrew X. Zhu, Karin G. Hoffmann, Nicole R. McMillian and Hema Sundar

Hepatobiliary cancers include a spectrum of invasive carcinomas arising in the liver (hepatocellular carcinoma), gall bladder, and bile ducts (cholangiocarcinomas). Gallbladder cancer and cholangiocarcinomas are collectively known as biliary tract cancers. Gallbladder cancer is the most common and aggressive type of all the biliary tract cancers. Cholangiocarcinomas are diagnosed throughout the biliary tree and are typically classified as either intrahepatic or extrahepatic cholangiocarcinoma. Extrahepatic cholangiocarcinomas are more common than intrahepatic cholangiocarcinomas. This manuscript focuses on the clinical management of patients with gallbladder cancer and cholangiocarcinomas (intrahepatic and extrahepatic).