310 results on '"Adam C. Yopp"'
Search Results
2. The phosphatidylserine targeting antibody bavituximab plus pembrolizumab in unresectable hepatocellular carcinoma: a phase 2 trial
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David Hsiehchen, Muhammad S. Beg, Radhika Kainthla, Jay Lohrey, Syed M. Kazmi, Leticia Khosama, Mary Claire Maxwell, Heather Kline, Courtney Katz, Asim Hassan, Naoto Kubota, Ellen Siglinsky, Anil K. Pillai, Hagop Youssoufian, Colleen Mockbee, Kerry Culm, Mark Uhlik, Laura Benjamin, Rolf A. Brekken, Chul Ahn, Amit G. Singal, Hao Zhu, Yujin Hoshida, and Adam C. Yopp
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Science - Abstract
Abstract Immune checkpoint inhibitors targeting PD-1/L1 have modest efficacy in hepatocellular carcinoma as single agents. Targeting membranous phosphatidylserine may induce pro-inflammatory and -immune stimulating effects that enhance immunotherapy activity. This hypothesis was tested in a single-arm phase 2 trial evaluating frontline bavituximab, a phosphatidylserine targeting antibody, plus pembrolizumab (anti-PD-1) in patients with unresectable hepatocellular carcinoma (NCT03519997). The primary endpoint was investigator-assessed objective response rate among evaluable patients, and secondary end points included progression-free survival, incidence of adverse events, overall survival, and duration of response. Among 28 evaluable patients, the confirmed response rate was 32.1%, which met the pre-specified endpoint, and the median progression-free survival was 6.3 months (95% CI, 1.3–11.3 months). Treatment related-adverse events of any grade occurred in 45.7% of patients, with grade 3 or greater adverse events in 14.3% of patients. Adverse events of any cause were observed in 33 patients (94.3%), with grade 3 or greater adverse events in 11 patients (31.4%). Prespecified exploratory analyses of baseline tumor specimens showed that a depletion of B cells, and the presence of fibrotic tissue and expression of immune checkpoints in stroma was associated with tumor response. These results suggest that targeting phosphatidylserine may lead to synergistic effects with PD-1 blockade without increasing toxicity rates, and future studies on this therapeutic strategy may be guided by biomarkers characterizing the pre-treatment tumor microenvironment.
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- 2024
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3. Lenvatinib inhibits the growth of gastric cancer patient-derived xenografts generated from a heterogeneous population
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John D. Karalis, Lynn Y. Yoon, Suntrea T. G. Hammer, Changjin Hong, Min Zhu, Ibrahim Nassour, Michelle R. Ju, Shu Xiao, Esther C. Castro-Dubon, Deepak Agrawal, Jorge Suarez, Scott I. Reznik, John C. Mansour, Patricio M. Polanco, Adam C. Yopp, Herbert J. Zeh, Tae Hyun Hwang, Hao Zhu, Matthew R. Porembka, and Sam C. Wang
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Gastric cancer ,Patient-derived xenograft ,PDX ,Lenvatinib ,NSG mice ,Nude mice ,Medicine - Abstract
Abstract Background Lenvatinib is a multitargeted tyrosine kinase inhibitor that is being tested in combination with immune checkpoint inhibitors to treat advanced gastric cancer; however, little data exists regarding the efficacy of lenvatinib monotherapy. Patient-derived xenografts (PDX) are established by engrafting human tumors into immunodeficient mice. The generation of PDXs may be hampered by growth of lymphomas. In this study, we compared the use of mice with different degrees of immunodeficiency to establish PDXs from a diverse cohort of Western gastric cancer patients. We then tested the efficacy of lenvatinib in this system. Methods PDXs were established by implanting gastric cancer tissue into NOD.Cg-Prkdc scid Il2rg tm1Wjl /SzJ (NSG) or Foxn1 nu (nude) mice. Tumors from multiple passages from each PDX line were compared histologically and transcriptomically. PDX-bearing mice were randomized to receive the drug delivery vehicle or lenvatinib. After 21 days, the percent tumor volume change (%Δvtumor) was calculated. Results 23 PDX models were established from Black, non-Hispanic White, Hispanic, and Asian gastric cancer patients. The engraftment rate was 17% (23/139). Tumors implanted into NSG (16%; 18/115) and nude (21%; 5/24) mice had a similar engraftment rate. The rate of lymphoma formation in nude mice (0%; 0/24) was lower than in NSG mice (20%; 23/115; p
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- 2022
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4. Hepatocellular Carcinoma Screening Process Failures in Patients with Cirrhosis
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Patrick Marquardt, Po‐Hong Liu, Joshua Immergluck, Jocelyn Olivares, Ana Arroyo, Nicole E. Rich, Neehar D. Parikh, Adam C. Yopp, and Amit G. Singal
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Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Professional society guidelines recommend semiannual screening for hepatocellular carcinoma (HCC) in patients with cirrhosis; however, studies suggest underuse of screening in clinical practice. Our study’s aim was to characterize reasons for HCC screening underuse among patients with cirrhosis. We conducted a retrospective cohort study of patients with cirrhosis diagnosed with HCC in two large health systems from 2011 to 2019. We classified screening receipt as consistent, inconsistent, or no screening in the year before HCC diagnosis. We categorized reasons for screening underuse as a potential failure at each of the following steps required for HCC screening: receipt of regular outpatient care, recognition of liver disease, recognition of cirrhosis, screening orders in patients with cirrhosis, and adherence to screening ultrasound appointments. Among 1,014 patients with cirrhosis with HCC, only 377 (37.2%) had regular outpatient care in the year before HCC presentation. Consistent screening was observed in 93 (24.7%) patients under regular outpatient care, whereas 161 (42.7%) had inconsistent screening and 123 (32.6%) no screening. We found screening underuse related to failures at each step in the screening process, although nearly half (49.6%) were due to lack of screening orders in patients with known cirrhosis. Conclusion: The most common reasons for HCC screening underuse in patients with cirrhosis are lack of regular outpatient care and lack of screening orders in those with known cirrhosis, highlighting the need for interventions targeted at these steps to increase HCC screening use.
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- 2021
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5. Evolving thresholds for liver transplantation in hepatocellular carcinoma: A Western experience
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Michelle R. Ju and Adam C. Yopp
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hepatocellular carcinoma ,liver transplant selection ,organ stewardship ,transplant criteria ,transplantation ,Surgery ,RD1-811 ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Abstract Hepatocellular carcinoma (HCC) is the second leading cause of cancer‐related deaths worldwide. Once considered an experimental treatment with dismal survival rates, liver transplantation for HCC entered a new era with the establishment of the Milan criteria over 20 years ago. In the modern post‐Milan‐criteria era, 5‐year survival outcomes are now upwards of 70% in select patients. Liver transplantation (LT) is now considered the optimal treatment for patients with moderate to severe cirrhosis and HCC, and the rates of transplantation in the United States are continuing to rise. Several expanded selection criteria have been proposed for determining which patients with HCC should be candidates for undergoing LT with similar overall and recurrence‐free survival rates to patients within the Milan criteria. There is also a growing experience with downstaging of patients who fall outside conventional LT criteria at the time of HCC diagnosis with the goal of tumor shrinkage via locoregional therapies to become a candidate for transplantation. The aim of this review article is to characterize the various patient selection criteria for LT, discuss balancing organ stewardship with outcome measures in HCC patients, present evidence on the role of downstaging for large tumors, and explore future directions of LT for HCC.
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- 2020
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6. The Utility of Anatomical Liver Resection in Hepatocellular Carcinoma: Associated with Improved Outcomes or Lack of Supportive Evidence?
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Michelle Ju and Adam C. Yopp
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hepatocellular carcinoma ,hepatic resection ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths worldwide. Surgical resection of HCC remains one of the mainstays of curative therapies and is associated with five-year overall survival rates approaching 60%. Despite improved perioperative outcomes, locoregional recurrence within the first two years following hepatic resection is of significant concern with recurrence rates of up to 50%. The use of anatomical resection surgical approaches, whereby the portal venous blood flow is ligated proximal to the tumor bed, is postulated to reduce recurrence rates due to reduction of micrometastatic disease. The aim of this review is to characterize the definition of an anatomical resection (AR) during partial hepatectomy, discuss the theoretical advantages of AR during hepatic resection for HCC, and to present evidence of the impact of AR on outcome measures in patients with HCC. Based on current data, there is a lack of conclusive evidence to support the universal use of AR in cirrhotic patients with HCC. A randomized clinical trial is warranted to further clarify the debate between AR versus non-anatomical resection (NAR) for HCC.
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- 2019
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7. Primary gastric melanoma: case report of a rare malignancy
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Alexander Augustyn, Emma Diaz de Leon, and Adam C. Yopp
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melanoma, surgery, gastric, gastrointestinal ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
We report the case of a 64-year-old white male who presented to his primary care physician with complaints of fatigue. Physical exam was unremarkable and laboratory studies revealed profound anemia, for which the patient received a transfusion. Esophagogastroduodenoscopy revealed a bleeding mass in the proximal stomach that was histologically determined to be malignant melanoma, with immunohistochemical staining demonstrating positivity for SOX10, S100, MART-1, and HMG-45. After an extensive dermatological exam no other primary lesion was identified. Whole body positron emission tomography (18-FDG-PET/CT) demonstrated pathologic uptake only in the area of the proximal stomach. For this reason, primary gastric melanoma was suspected in this patient. The patient underwent subtotal gastrectomy with mass excision followed by Roux-en-Y reconstruction. Very few cases of primary gastric melanoma have been reported. We report this case and present diagnostic criteria for primary non-cutaneous melanoma and discuss potential non-surgical therapies.
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- 2015
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8. Rare Hepatic Arterial Anatomic Variants in Patients Requiring Pancreatoduodenectomy and Review of the Literature
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Smita Ramanadham, Seth M. Toomay, Adam C. Yopp, Glen C. Balch, Rohit Sharma, Roderich E. Schwarz, and John C. Mansour
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Surgery ,RD1-811 - Abstract
Normal hepatic arterial anatomy occurs in approximately 50–80% of cases; for the remaining cases, multiple variations have been described. Knowledge of these anomalies is especially important in hepatobiliary and pancreatic surgery in order to avoid unnecessary complications. We describe two cases of patients undergoing pancreatoduodenectomy for abnormalities in the head of the pancreas. Preoperative contrast-enhanced cross-sectional imaging demonstrated relevant, rare hepatic arterial variants: (1) a completely replaced hepatic arterial system with a gastroduodenal artery (GDA) arising directly from the celiac axis and (2) a replaced right hepatic artery originating from the superior mesenteric artery and traveling anterior to the pancreatic uncinate process and head. These findings were confirmed during pancreatoduodenectomy. Both of these variants have been rarely described with an incidence of
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- 2012
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9. An Overview of Clinical Trials in the Treatment of Resectable Hepatocellular Carcinoma
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Nicole M, Nevarez, Gloria Y, Chang, and Adam C, Yopp
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Carcinoma, Hepatocellular ,Oncology ,Liver Neoplasms ,Humans ,Hepatectomy ,Surgery ,Chemoembolization, Therapeutic ,Neoadjuvant Therapy - Abstract
Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related death worldwide. Partial hepatectomy, one of a few curative therapeutic modalities, is plagued by high recurrence rate of up to 70% at 5 years. Throughout the past 3 decades, many clinical trials have attempted to improve HCC recurrence rate following partial hepatectomy using adjuvant and neoadjuvant treatment modalities such as antiviral therapy, brachytherapy, systemic chemotherapy, immunotherapy, transarterial chemoembolization and radioembolization, and radiotherapy. The goal of this review is to discuss the clinical trials pertaining to resectable HCC including surgical technique considerations, adjuvant, and neoadjuvant treatment modalities.
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- 2023
10. Variation of Hepatocellular Carcinoma Treatment Patterns and Survival Across Geographic Regions in a Veteran Population
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Michelle R. Ju, John D. Karalis, Matthieu Chansard, M. Mathew Augustine, Eric Mortensen, Sam C. Wang, Matthew R. Porembka, Herbert J. Zeh, Adam C. Yopp, and Patricio M. Polanco
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Oncology ,Surgery - Published
- 2022
11. Factors associated with failure to operate and its impact on survival in early‐stage pancreatic cancer
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Gilbert Z. Murimwa, John D. Karalis, Jennie Meier, Mithin Nehrubabu, Micah Thornton, Matthew Porembka, Sam Wang, Herbert J. Zeh, Adam C. Yopp, and Patricio M. Polanco
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Oncology ,Surgery ,General Medicine - Published
- 2023
12. Multidisciplinary care for patients with HCC: a systematic review and meta-analysis
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Karim Seif El Dahan, Annika Reczek, Darine Daher, Nicole E. Rich, Ju Dong Yang, David Hsiehchen, Hao Zhu, Madhukar S. Patel, Maria del Pilar Bayona Molano, Nina Sanford, Purva Gopal, Neehar D. Parikh, Adam C. Yopp, and Amit G. Singal
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Hepatology - Published
- 2023
13. ASO Visual Abstract: Hospital Designations and Their Impact on Guideline-Concordant Care and Survival in Pancreatic Cancer: Do They Matter?
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Gilbert Z. Murimwa, John D. Karalis, Jennie Meier, Jingsheng Yan, Hong Zhu, Caitlin A. Hester, Matthew R. Porembka, Sam C. Wang, John C. Mansour, Herbert J. Zeh, Adam C. Yopp, and Patricio M. Polanco
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Oncology ,Surgery - Published
- 2023
14. Supplementary Table 1 from Failure Rates in the Hepatocellular Carcinoma Surveillance Process
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Jasmin A. Tiro, Jorge A. Marrero, William M. Lee, Mahendra Nehra, Eucharia Okolo, Ethan A. Halm, Celette Sugg Skinner, Samir Gupta, Adam C. Yopp, and Amit G. Singal
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DOC file, 30K, Definitions for Categories of Process Failures.
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- 2023
15. Supplementary Figure 1 from Failure Rates in the Hepatocellular Carcinoma Surveillance Process
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Jasmin A. Tiro, Jorge A. Marrero, William M. Lee, Mahendra Nehra, Eucharia Okolo, Ethan A. Halm, Celette Sugg Skinner, Samir Gupta, Adam C. Yopp, and Amit G. Singal
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PDF file, 64K, Study Population.
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- 2023
16. Trends and Disparities in Treatment Utilization for Early-Stage Hepatocellular Carcinoma in the Veteran Population
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Patricio M. Polanco, Michelle R. Ju, Matthieu Chansard, M. Mathew Augustine, Jennie Meier, Eric Mortensen, Herbert J. Zeh, and Adam C. Yopp
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Oncology ,Surgery - Published
- 2022
17. Disparities in Guideline-Concordant Treatment and Survival Among Border County Residents With Gastric Cancer
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Michelle R. Ju, Sam C. Wang, John C. Mansour, Patricio M. Polanco, Adam C. Yopp, Herbert J. Zeh, and Matthew R. Porembka
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Oncology ,Oncology (nursing) ,Health Policy - Abstract
PURPOSE: Previous studies have shown health disparities among US-Mexico border county (BC) residents. However, the impact of BC residence on gastric cancer treatment and survival outcomes is unknown. Our study compares the receipt of guideline-concordant care (GCC) and survival for patients with gastric cancer by BC status. METHODS: We conducted a retrospective review of adult non-Hispanic White and Hispanic patients with gastric adenocarcinoma diagnosed between 2004 and 2017 in the Texas Cancer Registry. Chi-square tests were used to compare categorical group differences, with pooled t-tests used to compare group means. The impact of BC residence on likelihood of receiving GCC was assessed with logistic regression. Overall survival was estimated using the Kaplan-Meier method and compared with log-rank tests. RESULTS: Our cohort consisted of 12,514 patients (15% BC). Overall, 45% of nonborder county residents received GCC versus 35% of BC residents ( P < .0001). After adjusting for age, race, stage, and insurance status, BC patients remained significantly less likely to receive GCC (odds ratio 0.69; 95% CI, 0.61 to 0.78). BC residence was associated with increased hazard of all-cause mortality after accounting for age, race, stage, poverty index, and treatment receipt (hazard ratio 1.11; 95% CI, 1.04 to 1.18). BC residents had significantly worse overall survival for localized and regional disease. CONCLUSION: BC residents with gastric cancer are less likely to receive GCC and have significantly worse survival outcomes than nonborder county residents. This highlights significant health care disparities arising from the lack of health care access and multiple social determinants of health. Further studies are needed to identify specific contributing mechanisms to improve health care equity.
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- 2022
18. Supplementary Table 3 from Hispanic/Latino Patients with Gastric Adenocarcinoma Have Distinct Molecular Profiles Including a High Rate of Germline CDH1 Variants
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Matthew R. Porembka, Tae Hyun Hwang, Hao Zhu, Adam C. Yopp, John C. Mansour, Scott I. Reznik, Deepak Agarwal, Jeanne Shen, Ibrahim Nassour, Lynn Y. Yoon, Jean R. Clemenceau, Changjin Hong, Min Zhu, Shu Xiao, Suntrea T.G. Hammer, Yunku Yeu, and Sam C. Wang
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Supplementary Table 3
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- 2023
19. Supplementary Data from Hispanic/Latino Patients with Gastric Adenocarcinoma Have Distinct Molecular Profiles Including a High Rate of Germline CDH1 Variants
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Matthew R. Porembka, Tae Hyun Hwang, Hao Zhu, Adam C. Yopp, John C. Mansour, Scott I. Reznik, Deepak Agarwal, Jeanne Shen, Ibrahim Nassour, Lynn Y. Yoon, Jean R. Clemenceau, Changjin Hong, Min Zhu, Shu Xiao, Suntrea T.G. Hammer, Yunku Yeu, and Sam C. Wang
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Supplementary Table Legend
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- 2023
20. Supplementary Table 1 from Hispanic/Latino Patients with Gastric Adenocarcinoma Have Distinct Molecular Profiles Including a High Rate of Germline CDH1 Variants
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Matthew R. Porembka, Tae Hyun Hwang, Hao Zhu, Adam C. Yopp, John C. Mansour, Scott I. Reznik, Deepak Agarwal, Jeanne Shen, Ibrahim Nassour, Lynn Y. Yoon, Jean R. Clemenceau, Changjin Hong, Min Zhu, Shu Xiao, Suntrea T.G. Hammer, Yunku Yeu, and Sam C. Wang
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Supplementary Table 1
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- 2023
21. Supplementary Table 2 from Hispanic/Latino Patients with Gastric Adenocarcinoma Have Distinct Molecular Profiles Including a High Rate of Germline CDH1 Variants
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Matthew R. Porembka, Tae Hyun Hwang, Hao Zhu, Adam C. Yopp, John C. Mansour, Scott I. Reznik, Deepak Agarwal, Jeanne Shen, Ibrahim Nassour, Lynn Y. Yoon, Jean R. Clemenceau, Changjin Hong, Min Zhu, Shu Xiao, Suntrea T.G. Hammer, Yunku Yeu, and Sam C. Wang
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Supplementary Table 2
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- 2023
22. Supplementary Table 4 from Hispanic/Latino Patients with Gastric Adenocarcinoma Have Distinct Molecular Profiles Including a High Rate of Germline CDH1 Variants
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Matthew R. Porembka, Tae Hyun Hwang, Hao Zhu, Adam C. Yopp, John C. Mansour, Scott I. Reznik, Deepak Agarwal, Jeanne Shen, Ibrahim Nassour, Lynn Y. Yoon, Jean R. Clemenceau, Changjin Hong, Min Zhu, Shu Xiao, Suntrea T.G. Hammer, Yunku Yeu, and Sam C. Wang
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Supplementary Table 4
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- 2023
23. Supplementary Figure 1 from Hispanic/Latino Patients with Gastric Adenocarcinoma Have Distinct Molecular Profiles Including a High Rate of Germline CDH1 Variants
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Matthew R. Porembka, Tae Hyun Hwang, Hao Zhu, Adam C. Yopp, John C. Mansour, Scott I. Reznik, Deepak Agarwal, Jeanne Shen, Ibrahim Nassour, Lynn Y. Yoon, Jean R. Clemenceau, Changjin Hong, Min Zhu, Shu Xiao, Suntrea T.G. Hammer, Yunku Yeu, and Sam C. Wang
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a. Age at the time of diagnosis of Hispanic/Latino (Hs/L) patients from this study, and of Asian and White patients analyzed by The Cancer Genome Atlas (TCGA). Horizontal lines, medians; boxes, interquartile ranges; whiskers, maximum and minimum values. P < 0.001. b. Second view of the principal component analysis of whole-exome sequencing data, as analyzed by Locating Ancestry from SEquence Reads to define patient ancestry of Asian and White patients analyzed by the TCGA and Hispanic/Latino patients from this study, as compared to reference from the Human Genome Diversity Project (HGDP).
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- 2023
24. Supplementary Methods from Hispanic/Latino Patients with Gastric Adenocarcinoma Have Distinct Molecular Profiles Including a High Rate of Germline CDH1 Variants
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Matthew R. Porembka, Tae Hyun Hwang, Hao Zhu, Adam C. Yopp, John C. Mansour, Scott I. Reznik, Deepak Agarwal, Jeanne Shen, Ibrahim Nassour, Lynn Y. Yoon, Jean R. Clemenceau, Changjin Hong, Min Zhu, Shu Xiao, Suntrea T.G. Hammer, Yunku Yeu, and Sam C. Wang
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Supplementary Methods
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- 2023
25. Supplementary Figure 4 from Hispanic/Latino Patients with Gastric Adenocarcinoma Have Distinct Molecular Profiles Including a High Rate of Germline CDH1 Variants
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Matthew R. Porembka, Tae Hyun Hwang, Hao Zhu, Adam C. Yopp, John C. Mansour, Scott I. Reznik, Deepak Agarwal, Jeanne Shen, Ibrahim Nassour, Lynn Y. Yoon, Jean R. Clemenceau, Changjin Hong, Min Zhu, Shu Xiao, Suntrea T.G. Hammer, Yunku Yeu, and Sam C. Wang
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a. Chromatograms confirming germline CDH1 mutations identified on whole-exome sequencing. b. Age of patients who are wild-type for CDH1 (blue) or carry germline CDH1 mutations (red). Bar denotes median.
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- 2023
26. Supplementary Figure 3 from Hispanic/Latino Patients with Gastric Adenocarcinoma Have Distinct Molecular Profiles Including a High Rate of Germline CDH1 Variants
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Matthew R. Porembka, Tae Hyun Hwang, Hao Zhu, Adam C. Yopp, John C. Mansour, Scott I. Reznik, Deepak Agarwal, Jeanne Shen, Ibrahim Nassour, Lynn Y. Yoon, Jean R. Clemenceau, Changjin Hong, Min Zhu, Shu Xiao, Suntrea T.G. Hammer, Yunku Yeu, and Sam C. Wang
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Subgroup analysis of overall survival for the Hispanic/Latino cohort. Kaplan-Meier curves comparing: a. all patients by individual mRNA clusters, P < 0.01, b. patients with genomically stable tumors, P < 0.05, c. patients with chromosomal instable tumors, P < 0.05, d. patients with diffuse-type tumors, P < 0.05, e. patients with intestinal-type tumors, P < 0.05.
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- 2023
27. Data from Hispanic/Latino Patients with Gastric Adenocarcinoma Have Distinct Molecular Profiles Including a High Rate of Germline CDH1 Variants
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Matthew R. Porembka, Tae Hyun Hwang, Hao Zhu, Adam C. Yopp, John C. Mansour, Scott I. Reznik, Deepak Agarwal, Jeanne Shen, Ibrahim Nassour, Lynn Y. Yoon, Jean R. Clemenceau, Changjin Hong, Min Zhu, Shu Xiao, Suntrea T.G. Hammer, Yunku Yeu, and Sam C. Wang
- Abstract
Hispanic/Latino patients have a higher incidence of gastric cancer and worse cancer-related outcomes compared with patients of other backgrounds. Whether there is a molecular basis for these disparities is unknown, as very few Hispanic/Latino patients have been included in previous studies. To determine the genomic landscape of gastric cancer in Hispanic/Latino patients, we performed whole-exome sequencing (WES) and RNA sequencing on tumor samples from 57 patients; germline analysis was conducted on 83 patients. The results were compared with data from Asian and White patients published by The Cancer Genome Atlas. Hispanic/Latino patients had a significantly larger proportion of genomically stable subtype tumors compared with Asian and White patients (65% vs. 21% vs. 20%, P < 0.001). Transcriptomic analysis identified molecular signatures that were prognostic. Of the 43 Hispanic/Latino patients with diffuse-type cancer, 7 (16%) had germline variants in CDH1. Variant carriers were significantly younger than noncarriers (41 vs. 50 years, P < 0.05). In silico algorithms predicted five variants to be deleterious. For two variants that were predicted to be benign, in vitro modeling demonstrated that these mutations conferred increased migratory capability, suggesting pathogenicity. Hispanic/Latino patients with gastric cancer possess unique genomic landscapes, including a high rate of CDH1 germline variants that may partially explain their aggressive clinical phenotypes. Individualized screening, genetic counseling, and treatment protocols based on patient ethnicity and race may be necessary.Significance:Gastric cancer in Hispanic/Latino patients has unique genomic profiles that may contribute to the aggressive clinical phenotypes seen in these patients.
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- 2023
28. Supplementary Figure 2 from Hispanic/Latino Patients with Gastric Adenocarcinoma Have Distinct Molecular Profiles Including a High Rate of Germline CDH1 Variants
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Matthew R. Porembka, Tae Hyun Hwang, Hao Zhu, Adam C. Yopp, John C. Mansour, Scott I. Reznik, Deepak Agarwal, Jeanne Shen, Ibrahim Nassour, Lynn Y. Yoon, Jean R. Clemenceau, Changjin Hong, Min Zhu, Shu Xiao, Suntrea T.G. Hammer, Yunku Yeu, and Sam C. Wang
- Abstract
a. The Cancer Genome Atlas algorithm to categorize gastric cancer into four molecular subtypes: Epstein-Barr virus infected (EBV, red), microsatellite instability (MSI, blue), chromosomal instability (CIN, purple), and genomically stable (GS, green). SCNA = somatic copy number alterations. b. MSIsensor score. Whole-exome sequence data from each Hispanic/Latino cancer sample were analyzed with MSIsenor. Gray bar denotes total mutation burden per megabase. Yellow bar denotes calculated MSIsensor score. Samples with score {greater than or equal to} 10 were considered to be microsatellite unstable.
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- 2023
29. Supplementary Figure 5 from Hispanic/Latino Patients with Gastric Adenocarcinoma Have Distinct Molecular Profiles Including a High Rate of Germline CDH1 Variants
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Matthew R. Porembka, Tae Hyun Hwang, Hao Zhu, Adam C. Yopp, John C. Mansour, Scott I. Reznik, Deepak Agarwal, Jeanne Shen, Ibrahim Nassour, Lynn Y. Yoon, Jean R. Clemenceau, Changjin Hong, Min Zhu, Shu Xiao, Suntrea T.G. Hammer, Yunku Yeu, and Sam C. Wang
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a. Immunohistochemistry for E-cadherin in six patients who have germline CDH1 mutations. Red long arrows denote cancer cells, short green arrows denote normal stomach glands. P: patient. For P16, normal stomach and cancer cells are shown in two separate panels. Scale bar = 50 μm. b. Amount of DNA in which the CDH1 promoter is methylated.
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- 2023
30. Supplementary Figure 6 from Hispanic/Latino Patients with Gastric Adenocarcinoma Have Distinct Molecular Profiles Including a High Rate of Germline CDH1 Variants
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Matthew R. Porembka, Tae Hyun Hwang, Hao Zhu, Adam C. Yopp, John C. Mansour, Scott I. Reznik, Deepak Agarwal, Jeanne Shen, Ibrahim Nassour, Lynn Y. Yoon, Jean R. Clemenceau, Changjin Hong, Min Zhu, Shu Xiao, Suntrea T.G. Hammer, Yunku Yeu, and Sam C. Wang
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Immunofluorescence staining for E-cadherin in Chinese hamster ovary cells overexpressing wild-type (WT) CDH1, A286G, or G1849A variants, all of which have wild-type membranous localization. Scale bar = 10 μm.
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- 2023
31. Hospital Designations and Their Impact on Guideline-Concordant Care and Survival in Pancreatic Cancer. Do They Matter?
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Gilbert Z. Murimwa, John D. Karalis, Jennie Meier, Jingsheng Yan, Hong Zhu, Caitlin A. Hester, Matthew R. Porembka, Sam C. Wang, John C. Mansour, Herbert J. Zeh, Adam C. Yopp, and Patricio M. Polanco
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Oncology ,Surgery - Published
- 2023
32. Nativity Status is an Important Social Determinant of Health for Hispanic Patients with Gastric Cancer in Texas
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Michelle R. Ju, John D. Karalis, Archana Bhat, Hong Zhu, Timothy Hogan, Courtney Balentine, Adam C. Yopp, Patricio M. Polanco, Sam C. Wang, Herbert J. Zeh, and Matthew R. Porembka
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Oncology ,Surgery - Published
- 2022
33. Treatment and Survival Disparities of Colon Cancer in the Texas-Mexico Border Population: Cancer Disparities in Border Population
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Matthew R. Porembka, Hong Zhu, Sam C. Wang, Adam C. Yopp, Justin Yan, Caitlin A. Hester, Patricio M. Polanco, Matthew M. Augustine, Jingsheng Yan, Herbert J. Zeh, and John C. Mansour
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medicine.medical_specialty ,education.field_of_study ,business.industry ,Colorectal cancer ,Optimal treatment ,Population ,Medicare ,medicine.disease ,Texas ,United States ,Cancer registry ,Treatment utilization ,Internal medicine ,Colonic Neoplasms ,medicine ,Humans ,Vulnerable population ,Cancer disparities ,Surgery ,Healthcare Disparities ,Risk factor ,education ,business ,Mexico ,Aged - Abstract
Previous studies have reported healthcare disparities in the Texas-Mexico border population. Our aim was to evaluate treatment utilization and oncologic outcomes of colon cancer patients in this vulnerable population.Patients with localized and regional colon cancer (CC) were identified in the Texas Cancer Registry (1995-2016). Clinicopathological data, hospital factors, receipt of optimal treatment, and overall survival (OS) were compared between Texas-Mexico Border (TMB) and the Non-Texas-Mexico Border (NTMB) cohorts. Multivariable analysis was performed to identify risk factors associated with decreased survival.We identified 43,557 patients with localized/regional CC (9% TMB and 91% NTMB). TMB patients were more likely to be Hispanic (73% versus 13%), less likely to have private insurance (13% versus 21%), were more often treated at safety net hospitals (82% versus 22%) and less likely at ACS-CoC accredited hospitals (32% versus 57%). TMB patients were more likely to receive suboptimal treatment (21% versus 16%) and had a lower median OS for localized (8.58 versus 9.58 y) and regional colon cancer (5.75 versus 6.18 y, all P0.001). In multivariable analysis, TMB status was not associated with worse OS. Factors associated with worse survival included receipt of suboptimal treatment, Medicare/insured status, and treatment in safety net and non-accredited ACS-CoC hospitals (all P0.001) CONCLUSIONS: While TMB CC patients had worse OS, TMB status itself was not found to be a risk factor for decreased survival. This survival disparity is likely associated with higher rate of suboptimal treatment, Medicare/Uninsured status, and decreased access to ACS-CoC accredited hospitals.
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- 2021
34. Socioeconomic and racial/ethnic disparities in receipt of palliative care among patients with metastatic hepatocellular carcinoma
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John C. Mansour, Matthew R. Porembka, Adam C. Yopp, Sam C. Wang, Rodrigo E. Alterio, and Michelle R. Ju
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Male ,Oncology ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,Palliative care ,Logistic regression ,Liver disease ,Internal medicine ,Ethnicity ,medicine ,Humans ,Healthcare Disparities ,Socioeconomic status ,Aged ,Retrospective Studies ,business.industry ,Liver Neoplasms ,Palliative Care ,Cancer ,General Medicine ,Odds ratio ,Middle Aged ,Prognosis ,medicine.disease ,Combined Modality Therapy ,Confidence interval ,Survival Rate ,Socioeconomic Factors ,Hepatocellular carcinoma ,Quality of Life ,Female ,Surgery ,business ,Follow-Up Studies - Abstract
Background Patients with metastatic hepatocellular carcinoma (HCC) suffer symptoms of both end-stage liver disease and cancer. Palliative care (PC) enhances the quality of life via symptom control and even improves survival for some cancers. Our study characterized rates of PC utilization among metastatic HCC patients and determined factors associated with PC receipt. Methods We conducted a retrospective review of adult National Cancer Database patients diagnosed with metastatic HCC between 2004 and 2016. Chi-square tests were used to analyze two cohorts: those who received PC and those who did not. Logistic regression was performed to assess the impact of clinicodemographic factors on the likelihood of receiving PC. Results PC utilization was low at just 17%. Later year of diagnosis, insured status, and higher education level were associated with an increased likelihood of receiving PC. Treatment at academic centers or integrated network cancer programs increased the likelihood of receiving PC compared to treatment at a community center (odds ratio [OR] = 1.17, 95% confidence interval [CI] = 1.03-1.33 and OR = 1.25, 95% CI = 1.07-1.45; respectively). Hispanics were significantly less likely to received PC than non-Hispanic Whites (OR = 0.73, 95% CI = 0.64-0.82). Conclusions PC utilization among patients with metastatic HCC remains low. Targeted efforts should be enacted to increase the delivery of PC in this group.
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- 2021
35. Diagnostic and Therapeutic Delays in Patients With Hepatocellular Carcinoma
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Ashwin Rao, Amit G. Singal, Jorge A. Marrero, Adam C. Yopp, and Nicole E. Rich
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medicine.medical_specialty ,Carcinoma, Hepatocellular ,Logistic regression ,03 medical and health sciences ,0302 clinical medicine ,Interquartile range ,Internal medicine ,Humans ,Medicine ,Clinical significance ,In patient ,Pandemics ,Retrospective Studies ,SARS-CoV-2 ,business.industry ,Liver Neoplasms ,Hazard ratio ,COVID-19 ,Cancer ,Retrospective cohort study ,medicine.disease ,Oncology ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,030211 gastroenterology & hepatology ,business - Abstract
Background: Delays in diagnosis and treatment have been reported for many cancers, with resultant stage migration and worse survival; however, few data exist in patients with hepatocellular carcinoma (HCC). These data are of particular importance in light of the COVID-19 pandemic, which has caused disruptions in healthcare processes and may continue to impact cancer care for the foreseeable future. The aim of our study was to characterize the prevalence and clinical significance of diagnostic and treatment delays in patients with HCC. Methods: We performed a retrospective cohort study of consecutive patients diagnosed with HCC between January 2008 and July 2017 at 2 US health systems. Diagnostic and treatment delays were defined as >90 days between presentation and HCC diagnosis and between diagnosis and treatment, respectively. We used multivariable logistic regression to identify factors associated with diagnostic and treatment delays and Cox proportional hazard models to identify correlates of overall survival. Results: Of 925 patients with HCC, 39.0% were diagnosed via screening, 33.1% incidentally, and 27.9% symptomatically. Median time from presentation to diagnosis was 37 days (interquartile range, 18–94 days), with 120 patients (13.0%) experiencing diagnostic delays. Median time from HCC diagnosis to treatment was 46 days (interquartile range, 29–74 days), with 17.2% of patients experiencing treatment delays. Most (72.5%) diagnostic delays were related to provider-level factors (eg, monitoring indeterminate nodules), whereas nearly half (46.2%) of treatment delays were related to patient-related factors (eg, missed appointments). In multivariable analyses, treatment delays were not associated with increased mortality (hazard ratio, 0.90; 95% CI, 0.60–1.35); these results were consistent across subgroup analyses by Barcelona Clinic Liver Cancer stage and treatment modality. Conclusions: Diagnostic and therapeutic delays exceeding 3 months are common in patients with HCC; however, observed treatment delays do not seem to significantly impact overall survival.
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- 2021
36. Hepatocellular Carcinoma Screening Process Failures in Patients with Cirrhosis
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Joshua Immergluck, Neehar D. Parikh, Po Hong Liu, Nicole E. Rich, Jocelyn Olivares, Ana B. Arroyo, Amit G. Singal, Patrick Marquardt, and Adam C. Yopp
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medicine.medical_specialty ,Cirrhosis ,Hepatology ,business.industry ,Psychological intervention ,MEDLINE ,Retrospective cohort study ,Original Articles ,RC799-869 ,Diseases of the digestive system. Gastroenterology ,medicine.disease ,digestive system diseases ,Liver disease ,Ambulatory care ,Hepatocellular carcinoma ,Internal medicine ,medicine ,In patient ,Original Article ,business - Abstract
Professional society guidelines recommend semiannual screening for hepatocellular carcinoma (HCC) in patients with cirrhosis; however, studies suggest underuse of screening in clinical practice. Our study’s aim was to characterize reasons for HCC screening underuse among patients with cirrhosis. We conducted a retrospective cohort study of patients with cirrhosis diagnosed with HCC in two large health systems from 2011 to 2019. We classified screening receipt as consistent, inconsistent, or no screening in the year before HCC diagnosis. We categorized reasons for screening underuse as a potential failure at each of the following steps required for HCC screening: receipt of regular outpatient care, recognition of liver disease, recognition of cirrhosis, screening orders in patients with cirrhosis, and adherence to screening ultrasound appointments. Among 1,014 patients with cirrhosis with HCC, only 377 (37.2%) had regular outpatient care in the year before HCC presentation. Consistent screening was observed in 93 (24.7%) patients under regular outpatient care, whereas 161 (42.7%) had inconsistent screening and 123 (32.6%) no screening. We found screening underuse related to failures at each step in the screening process, although nearly half (49.6%) were due to lack of screening orders in patients with known cirrhosis. Conclusion: The most common reasons for HCC screening underuse in patients with cirrhosis are lack of regular outpatient care and lack of screening orders in those with known cirrhosis, highlighting the need for interventions targeted at these steps to increase HCC screening use., In a retrospective cohort study of 1014 cirrhosis patients diagnosed with HCC in two large health systems, we categorized reasons for screening underuse: receipt of regular outpatient care, recognition of liver disease, recognition of cirrhosis, screening orders in patients with cirrhosis, and adherence to screening ultrasound appointments. Only 377 (37.2%) patients had regular outpatient care in the year prior to HCC presentation, of whom 93 (24.7%) had consistent screening, 161 (42.7%) had inconsistent screening, and 123 (32.6%) no screening. We found screening underuse related to failures at each step in the screening process, although nearly half (49.6%) were due to lack of screening orders in patients with known cirrhosis.
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- 2021
37. Challenging the Treatment Paradigm: Selecting Patients for Surgical Management of Hepatocellular Carcinoma with Portal Vein Tumor Thrombus
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Adam C. Yopp and Nicole M Nevarez
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medicine.medical_specialty ,business.industry ,Portal vein ,En bloc resection ,Review ,hepatocellular carcinoma ,Perioperative ,medicine.disease ,portal vein tumor thrombus ,digestive system diseases ,Surgery ,liver cancer ,Tumor thrombus ,Concomitant ,Hepatocellular carcinoma ,medicine ,Superior mesenteric vein ,business ,Liver cancer - Abstract
Portal vein tumor thrombus (PVTT) remains a common presentation in patients with hepatocellular carcinoma (HCC). Approximately 30–50% of patients newly diagnosed with HCC will present with a concomitant PVTT. Current guidelines recommend systemic therapy for treatment of HCC with PVTT. Real-world application of partial hepatectomy in HCC patients with PVTT has increased over the past two decades, as perioperative complications have declined. However, it is unclear if there is an association between the extent of PVTT and overall survival and rates of recurrence and whether the perioperative morbidity outweighs these potential benefits. Partial hepatectomy with en bloc resection of PVTT in second-order branches and distal can offer significant benefits in carefully selected patients; however, once the HCC-associated PVTT extends into first-order portal venous branches or more proximal into the superior mesenteric vein, the risks of surgical resection outweigh the benefits. The aim of this review is to determine which patients with HCC presenting with PVTT benefit from surgical resection. We will discuss the classification systems of PVTT and review both outcome and perioperative measures in patients undergoing partial hepatectomy with extirpation of HCC-related PVT.
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- 2021
38. Piperacillin-Tazobactam Compared With Cefoxitin as Antimicrobial Prophylaxis for Pancreatoduodenectomy
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Michael I. D’Angelica, Ryan J. Ellis, Jason B. Liu, Brian C. Brajcich, Mithat Gönen, Vanessa M. Thompson, Mark E. Cohen, Susan K. Seo, Emily C. Zabor, Michele L. Babicky, David J. Bentrem, Stephen W. Behrman, Kimberly A. Bertens, Scott A. Celinski, Carlos H. F. Chan, Mary Dillhoff, Matthew E. B. Dixon, Carlos Fernandez-del Castillo, Sepideh Gholami, Michael G. House, Paul J. Karanicolas, Harish Lavu, Shishir K. Maithel, John C. McAuliffe, Mark J. Ott, Bradley N. Reames, Dominic E. Sanford, Umut Sarpel, Courtney L. Scaife, Pablo E. Serrano, Travis Smith, Rebecca A. Snyder, Mark S. Talamonti, Sharon M. Weber, Adam C. Yopp, Henry A. Pitt, and Clifford Y. Ko
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General Medicine - Abstract
ImportanceDespite improvements in perioperative mortality, the incidence of postoperative surgical site infection (SSI) remains high after pancreatoduodenectomy. The effect of broad-spectrum antimicrobial surgical prophylaxis in reducing SSI is poorly understood.ObjectiveTo define the effect of broad-spectrum perioperative antimicrobial prophylaxis on postoperative SSI incidence compared with standard care antibiotics.Design, Setting, and ParticipantsPragmatic, open-label, multicenter, randomized phase 3 clinical trial at 26 hospitals across the US and Canada. Participants were enrolled between November 2017 and August 2021, with follow-up through December 2021. Adults undergoing open pancreatoduodenectomy for any indication were eligible. Individuals were excluded if they had allergies to study medications, active infections, chronic steroid use, significant kidney dysfunction, or were pregnant or breastfeeding. Participants were block randomized in a 1:1 ratio and stratified by the presence of a preoperative biliary stent. Participants, investigators, and statisticians analyzing trial data were unblinded to treatment assignment.InterventionThe intervention group received piperacillin-tazobactam (3.375 or 4 g intravenously) as perioperative antimicrobial prophylaxis, while the control group received cefoxitin (2 g intravenously; standard care).Main Outcomes and MeasuresThe primary outcome was development of postoperative SSI within 30 days. Secondary end points included 30-day mortality, development of clinically relevant postoperative pancreatic fistula, and sepsis. All data were collected as part of the American College of Surgeons National Surgical Quality Improvement Program.ResultsThe trial was terminated at an interim analysis on the basis of a predefined stopping rule. Of 778 participants (378 in the piperacillin-tazobactam group [median age, 66.8 y; 233 {61.6%} men] and 400 in the cefoxitin group [median age, 68.0 y; 223 {55.8%} men]), the percentage with SSI at 30 days was lower in the perioperative piperacillin-tazobactam vs cefoxitin group (19.8% vs 32.8%; absolute difference, −13.0% [95% CI, −19.1% to −6.9%]; P P = .02) and clinically relevant postoperative pancreatic fistula (12.7% vs 19.0%; difference, −6.3% [95% CI, −11.4% to −1.2%]; P = .03). Mortality rates at 30 days were 1.3% (5/378) among participants treated with piperacillin-tazobactam and 2.5% (10/400) among those receiving cefoxitin (difference, −1.2% [95% CI, −3.1% to 0.7%]; P = .32).Conclusions and RelevanceIn participants undergoing open pancreatoduodenectomy, use of piperacillin-tazobactam as perioperative prophylaxis reduced postoperative SSI, pancreatic fistula, and multiple downstream sequelae of SSI. The findings support the use of piperacillin-tazobactam as standard care for open pancreatoduodenectomy.Trial RegistrationClinicalTrials.gov Identifier: NCT03269994
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- 2023
39. Survival inequity in vulnerable populations with early-stage hepatocellular carcinoma: a United States safety-net collaborative analysis
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Emily L. Ryon, Sommer Luu, Joshua P. Kronenfeld, Annie Wang, Maria C. Russell, Neha Goel, Adam C. Yopp, Ann Y. Lee, David S. Goldberg, Eric J. Silberfein, Nipun B. Merchant, Rachel M. Lee, and Cary Hsu
- Subjects
Carcinoma, Hepatocellular ,Safety net ,MEDLINE ,Psychological intervention ,Vulnerable Populations ,Article ,03 medical and health sciences ,0302 clinical medicine ,Primary outcome ,medicine ,Health insurance ,Humans ,Retrospective Studies ,Treatment barriers ,Hepatology ,business.industry ,Liver Neoplasms ,Gastroenterology ,medicine.disease ,United States ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,Curative surgery ,030211 gastroenterology & hepatology ,business ,Safety-net Providers ,Demography - Abstract
BACKGROUND: Access to health insurance and curative interventions [surgery/liver directed therapy (LDT)] affects survival for early-stage hepatocellular carcinoma (HCC). The aim of this multi-institutional study of high-volume safety-net hospitals (SNHs) and their tertiary-academic-centers (AC) was to identify the impact of type/lack of insurance on survival disparities across hospitals, particularly SNHs whose mission is to minimize insurance related access to care barriers for vulnerable populations. METHODS: Early-stage HCC patients (2012-2014) from the US Safety-Net Collaborative were propensity-score matched by treatment at SNH/AC. Overall survival (OS) was the primary outcome. Multivariable Cox proportional-hazard analysis was performed accounting for sociodemographic and clinical parameters. RESULTS: Among 925 patients, those with no insurance (NI) had decreased curative surgery, compared to those with government insurance (GI) and private insurance [PI, (PI-SNH:60.5% vs. GI-SNH:33.1% vs. NI-SNH:13.6%, p
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- 2021
40. High Neutrophil–Lymphocyte Ratio and Delta Neutrophil–Lymphocyte Ratio Are Associated with Increased Mortality in Patients with Hepatocellular Cancer
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Amit G. Singal, Ana B. Arroyo, Nicole E. Rich, Marlyn J. Mayo, Hao Zhu, Arjmand R. Mufti, Yujin Hoshida, Takeshi Yokoo, Shannan R. Tujios, Thomas A. Kerr, Adam C. Yopp, Ju Dong Yang, Aarthi Parvathaneni, Jorge A. Marrero, Ahana Sen, William M. Lee, Mobolaji Odewole, Lafaine Grant, and Purva Gopal
- Subjects
medicine.medical_specialty ,Cirrhosis ,Physiology ,business.industry ,Lymphocyte ,fungi ,Gastroenterology ,Retrospective cohort study ,Hepatology ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,Internal medicine ,Cohort ,medicine ,Biomarker (medicine) ,030211 gastroenterology & hepatology ,Liver cancer ,business - Abstract
The neutrophil–lymphocyte ratio (NLR) has been proposed as a prognostic biomarker for cirrhosis and non-liver malignancies. We aimed to evaluate the prognostic value of NLR in a diverse cohort of patients with hepatocellular carcinoma (HCC). We performed a retrospective study of patients diagnosed with HCC between 2008 and 2017 at two large US health systems. We used Cox proportional hazard and multivariable ordinal logistic regression models to identify factors associated with overall survival and response to first HCC treatment, respectively. Primary variables of interest were baseline NLR and delta NLR, defined as the difference between pre- and post-treatment NLR. Among 1019 HCC patients, baseline NLR was 200 ng/mL (45.6% vs 33.8%). Baseline NLR ≥ 5 was independently associated with higher mortality (median survival 4.3 vs 15.1 months; adjusted HR 1.70, 95%CI 1.41–2.06), with differences in survival consistent across BCLC stages. After adjusting for baseline covariates including NLR, delta NLR > 0.26 was also independently associated with increased mortality (HR 1.42, 95%CI 1.14–1.78). In a secondary analysis, high NLR was associated with lower odds of response to HCC treatment (20.2% vs 31.6%; adjusted OR 0.55, 95%CI 0.32–0.95). In a large Western cohort of patients with HCC, high baseline NLR and delta NLR were independent predictors of mortality. NLR is an inexpensive test that may be a useful component of future HCC prognostic models.
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- 2021
41. Hepatobiliary Cancers, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology
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Daniel E. Abbott, Al B. Benson, Cindy Hochstetler, Jordan M. Cloyd, Matthew H. Levine, Michael I. D’Angelica, Robin D. Kim, Robert A. Anders, Steven S. Raman, Prabhleen Chahal, Stacey Stein, Manisha Palta, Sanjay S. Reddy, Melinda Bachini, Jean Nicolas Vauthey, Mitesh J. Borad, Anne M. Covey, Rojymon Jacob, William G. Hawkins, Gagandeep Singh, Daniel A. Anaya, Adam C. Yopp, Nicole R. McMillian, Susan Darlow, R. Kate Kelley, Alan P. Venook, Renuka Iyer, Daniel B. Brown, James O. Park, Evan S. Glazer, Vaibhav Sahai, Chandrakanth Are, Daniel T. Chang, Tracey E. Schefter, Adam M. Burgoyne, and Lipika Goyal
- Subjects
Oncology ,Sorafenib ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,Bevacizumab ,03 medical and health sciences ,0302 clinical medicine ,Atezolizumab ,Internal medicine ,medicine ,Carcinoma ,Humans ,Gallbladder cancer ,neoplasms ,business.industry ,Liver Neoplasms ,Cancer ,medicine.disease ,digestive system diseases ,Regimen ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,030211 gastroenterology & hepatology ,business ,medicine.drug - Abstract
The NCCN Guidelines for Hepatobiliary Cancers focus on the screening, diagnosis, staging, treatment, and management of hepatocellular carcinoma (HCC), gallbladder cancer, and cancer of the bile ducts (intrahepatic and extrahepatic cholangiocarcinoma). Due to the multiple modalities that can be used to treat the disease and the complications that can arise from comorbid liver dysfunction, a multidisciplinary evaluation is essential for determining an optimal treatment strategy. A multidisciplinary team should include hepatologists, diagnostic radiologists, interventional radiologists, surgeons, medical oncologists, and pathologists with hepatobiliary cancer expertise. In addition to surgery, transplant, and intra-arterial therapies, there have been great advances in the systemic treatment of HCC. Until recently, sorafenib was the only systemic therapy option for patients with advanced HCC. In 2020, the combination of atezolizumab and bevacizumab became the first regimen to show superior survival to sorafenib, gaining it FDA approval as a new frontline standard regimen for unresectable or metastatic HCC. This article discusses the NCCN Guidelines recommendations for HCC.
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- 2021
42. Long-Term Results of a Phase 1 Dose-Escalation Trial and Subsequent Institutional Experience of Single-Fraction Stereotactic Ablative Radiation Therapy for Liver Metastases
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Robert Timmerman, Nina N. Sanford, Todd A. Aguilera, Jeffrey J Meyer, Michael R. Folkert, William G. Rule, Lucien A. Nedzi, Takeshi Yokoo, Raquibul Hannan, Patricio M. Polanco, John C. Mansour, and Adam C. Yopp
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Adult ,Male ,Organs at Risk ,Cancer Research ,medicine.medical_specialty ,Time Factors ,Maximum Tolerated Dose ,medicine.medical_treatment ,Radiosurgery ,SABR volatility model ,030218 nuclear medicine & medical imaging ,Lesion ,03 medical and health sciences ,0302 clinical medicine ,Ablative case ,Dose escalation ,Humans ,Medicine ,Radiology, Nuclear Medicine and imaging ,Aged ,Aged, 80 and over ,Radiation ,business.industry ,Liver Neoplasms ,Radiotherapy Dosage ,Long term results ,Middle Aged ,Magnetic Resonance Imaging ,Progression-Free Survival ,Single fraction ,Tumor Burden ,Radiation therapy ,Treatment Outcome ,Liver ,Oncology ,030220 oncology & carcinogenesis ,Cohort ,Female ,Radiology ,medicine.symptom ,business ,Follow-Up Studies - Abstract
We report long-term outcomes from our phase 1 dose-escalation study to determine the maximum tolerated dose of single-fraction liver SABR pooled with our subsequent single institutional experience with patients treated postprotocol at the highest dose level (40 Gy) established from the phase 1 study.Patients with liver metastases from solid tumors located outside of the central liver zone were treated with single-fraction SABR on a phase 1 dose escalation trial. At least 700 cc of normal liver had to receive9.1 Gy. Seven patients with 10 liver metastases received the initial prescription dose of 35 Gy, and dose was then escalated to 40 Gy for 7 more patients with 7 liver metastases. An additional 19 postprotocol patients with 22 liver metastases were treated to 40 Gy in a single fraction. Patients were followed for toxicity and underwent serial imaging to assess local control.Median imaging follow-up for the combined cohort (n = 33, 39 lesions) was 25.9 months; 38.9 months for protocol patients and 20.2 months for postprotocol patients. Median lesion size was 2.0 cm (range, 0.5-5.0 cm). There were no dose-limiting toxicities observed for protocol patients, and only 3 grade 2 toxicities were observed in the entire cohort, with no grade ≥3 toxicities attributable to treatment. Four-year actuarial local control of irradiated lesions in the entire cohort was 96.6%, 100% in the protocol group and 92.9% in the subsequent patients. Two-year overall survival for all treated patients was 82.0%.For selected patients with liver metastases, single-fraction SABR at doses of 35 and 40 Gy was safe and well-tolerated, and shows excellent local control with long-term follow-up; results in subsequent patients treated with single-fraction SABR doses of 40 Gy confirmed our earlier results.
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- 2021
43. LI-RADS treatment response algorithm after first-line DEB-TACE: reproducibility and prognostic value at initial post-treatment CT/MRI
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Robert C. Sibley, Ali Pirasteh, Abhinav Vij, Amit G. Singal, Hector Marquez, Adam C. Yopp, Julia R. Fielding, Takeshi Yokoo, E. Aleks Sorra, Gaurav Khatri, Ana B. Arroyo, and Nicole E. Rich
- Subjects
Reproducibility ,medicine.medical_specialty ,Treatment response ,Radiological and Ultrasound Technology ,medicine.diagnostic_test ,Proportional hazards model ,business.industry ,Urology ,Gastroenterology ,Magnetic resonance imaging ,Retrospective cohort study ,Hepatology ,medicine.disease ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,Response Evaluation Criteria in Solid Tumors ,030220 oncology & carcinogenesis ,Internal medicine ,Hepatocellular carcinoma ,medicine ,Radiology, Nuclear Medicine and imaging ,business ,Algorithm - Abstract
To evaluate the inter-reader reproducibility and prognostic accuracy of the Liver Imaging Reporting and Data System (LI-RADS) treatment response algorithm (LR-TR) at the time of initial post-treatment evaluation following drug-eluting beads transarterial chemoembolization (DEB-TACE) for hepatocellular carcinoma (HCC). This retrospective study included patients with HCC who underwent first-line DEB-TACE between January 2011 and December 2015. Six readers (three fellowship-trained radiologists and three radiology trainees) independently assessed lesion-level response in up to two treated lesions per LR-TR and modified Response Evaluation Criteria in Solid Tumors (mRECIST)-target criteria, as well as patient-level response per mRECIST-overall criteria, on the initial post-treatment CT/MRI. Inter-reader agreement was calculated by Fleiss’ multi-reader κ. We tested whether LR-TR, mRECIST-target, and mRECIST-overall response were associated with overall survival using Kaplan–Meier and Cox proportional hazard model analyses. A total of 82 patients with 113 treated target lesions were included. Inter-reader agreement was moderate for LR-TR and mRECIST-overall (κ range 0.42–0.57), and substantial for mRECIST-target (κ range 0.62–0.66), among all three reader-groups: all readers, experienced readers, and less-experienced readers. LR-TR and mRECIST-target response were not significantly associated with overall survival regardless of reader experience (P > 0.05). In contrast, mRECIST-overall response was significantly associated with overall survival when assessed by all readers (P = 0.02) and experienced readers (P = 0.03), but not by the less-experienced readers (P = 0.35). Although LR-TR algorithm has moderate inter-reader reproducibility, it alone may not predict overall survival on the initial post-treatment CT/MRI after first-line DEB-TACE for HCC.
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- 2021
44. Impact of hepatitis C treatment on long-term outcomes for patients with hepatocellular carcinoma: a United States Safety Net Collaborative Study
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Shishir K. Maithel, Eric J. Silberfein, Cary Hsu, Maria C. Russell, Emily L. Ryon, Annie Wang, Rachel M. Lee, Sommer Luu, Michael K. Turgeon, Neha Goel, Adam C. Yopp, Adriana C. Gamboa, and Ann Y. Lee
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medicine.medical_specialty ,Carcinoma, Hepatocellular ,Referral ,medicine.medical_treatment ,Improved survival ,Article ,Resection ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Long term outcomes ,Humans ,Stage (cooking) ,Retrospective Studies ,Chemotherapy ,Hepatology ,business.industry ,Liver Neoplasms ,Gastroenterology ,virus diseases ,Hepatitis C ,medicine.disease ,United States ,digestive system diseases ,Liver Transplantation ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,030211 gastroenterology & hepatology ,business - Abstract
BACKGROUND: Widespread HCV treatment for hepatocellular carcinoma (HCC) patients remains limited. Our aim was to evaluate the association of HCV treatment with survival and assess barriers to treatment. METHODS: Patients in the U.S. Safety Net Collaborative with HCV and HCC were included. Primary outcome was overall survival (OS). Secondary outcomes were recurrence-free survival (RFS) and barriers to receiving HCV treatment. RESULTS: Of 941 patients, 57% received care at tertiary referral centers (n=533), 74% did not receive HCV treatment (n=696), 6% underwent resection (n=54), 17% liver transplant (n=163), 50% liver-directed therapy (n=473), and 7% chemotherapy (n=60). HCV treatment was associated with improved OS compared to no HCV treatment (70 vs 21 months, p
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- 2021
45. Cumulative GRAS Score as a Predictor of Survival After Resection for Adrenocortical Carcinoma: Analysis From the U.S. Adrenocortical Carcinoma Database
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Quan-Yang Duh, Sean Ronnekleiv-Kelly, George A. Poultsides, Jason D. Prescott, Paula Marincola Smith, Jason A. Glenn, Edward A. Levine, Lauren M. Postlewait, John C. Mansour, Tracy S. Wang, Daniel E. Abbott, Jason K. Sicklick, Natalie Seiser, Shishir K. Maithel, Ioannis Hatzaras, Adam C. Yopp, Konstantinos I. Votanopoulos, Rivfka Shenoy, Colleen M. Kiernan, John E. Phay, Thuy B. Tran, Linda X. Jin, Lawrence A. Shirley, Carmen C. Solorzano, Timothy M. Pawlik, Jordan J. Baechle, and Ryan C. Fields
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Adult patients ,Database ,Positive margin ,business.industry ,Retrospective cohort study ,030230 surgery ,computer.software_genre ,Malignancy ,medicine.disease ,Resection ,03 medical and health sciences ,Tumor grade ,0302 clinical medicine ,Oncology ,Surgical oncology ,030220 oncology & carcinogenesis ,Medicine ,Adrenocortical carcinoma ,Surgery ,business ,computer - Abstract
Adrenocortical carcinoma (ACC) is a rare but aggressive malignancy, and many prognostic factors that influence survival remain undefined. Individually, the GRAS (Grade, Resection status, Age, and Symptoms of hormone hypersecretion) parameters have demonstrated their prognostic value in ACC. This study aimed to assess the value of a cumulative GRAS score as a prognostic indicator after ACC resection. A retrospective cohort study of adult patients who underwent surgical resection for ACC between 1993 and 2014 was performed using the United States Adrenocortical Carcinoma Group (US-ACCG) database. A sum GRAS score was calculated for each patient by adding one point each when the criteria were met for tumor grade (Weiss criteria ≥ 3 or Ki67 ≥ 20%), resection status (micro- or macroscopically positive margin), age (≥ 50 years), and preoperative symptoms of hormone hypersecretion (present). Overall survival (OS) and disease-free survival (DFS) by cumulative GRAS score were analyzed by the Kaplan–Meier method and log-rank test. Of the 265 patients in the US-ACCG database, 243 (92%) had sufficient data available to calculate a cumulative GRAS score and were included in this analysis. The 265 patients comprised 23 patients (10%) with a GRAS of 0, 52 patients (21%) with a GRAS of 1, 92 patients (38%) with a GRAS of 2, 63 patients (26%) with a GRAS of 3, and 13 patients (5%) with a GRAS of 4. An increasing GRAS score was associated with shortened OS (p < 0.01) and DFS (p < 0.01) after index resection. In this retrospective analysis, the cumulative GRAS score effectively stratified OS and DFS after index resection for ACC. Further prospective analysis is required to validate the cumulative GRAS score as a prognostic indicator for clinical use.
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- 2021
46. Redefining High-Volume Gastric Cancer Centers: The Impact of Operative Volume on Surgical Outcomes
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Michelle R. Ju, James Michael Blackwell, Herbert J. Zeh, Matthew R. Porembka, Sam C. Wang, and Adam C. Yopp
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medicine.medical_specialty ,business.industry ,Proportional hazards model ,medicine.medical_treatment ,Hazard ratio ,Cancer ,Odds ratio ,medicine.disease ,Confidence interval ,Surgery ,03 medical and health sciences ,0302 clinical medicine ,Oncology ,Surgical oncology ,030220 oncology & carcinogenesis ,Cohort ,medicine ,030211 gastroenterology & hepatology ,Gastrectomy ,business - Abstract
Performance of technically complex surgery at high-volume (HV) centers is associated with improved outcomes. The aim of this study was to assess whether hospital gastrectomy volume is associated with surgical outcomes, and what threshold of case volume meaningfully impacts surgical outcomes. We conducted a retrospective review of adult NCDB patients with gastric adenocarcinoma undergoing gastrectomy between 2004 and 2015. A multivariable Cox proportional hazards model with restricted cubic splines was used to examine the association of annual hospital gastrectomy volume and overall survival. Bootstrap simulation was used to estimate the cut-point corresponding to maximum change in log hazard ratio. Hospitals were divided into HV (≥ 17 cases/year) and low-volume (LV
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- 2021
47. Inaccurate Clinical Stage Is Common for Gastric Adenocarcinoma and Is Associated with Undertreatment and Worse Outcomes
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Patricio M. Polanco, John D. Karalis, Herbert J. Zeh, James Michael Blackwell, Matthew R. Porembka, Michelle R. Ju, Adam C. Yopp, John C. Mansour, Mathew M. Augustine, and Sam C. Wang
- Subjects
Oncology ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Cancer ,Disease ,030230 surgery ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,Surgical oncology ,030220 oncology & carcinogenesis ,Internal medicine ,Adjuvant therapy ,Medicine ,Surgery ,Gastrectomy ,Stage (cooking) ,business ,Survival analysis ,Neoadjuvant therapy - Abstract
Accurate clinical staging (CS) of gastric cancer is critical for appropriate treatment selection and prognostication, but CS remains highly imprecise. Our study evaluates factors associated with inaccurate CS, the impact of inaccurate CS on outcomes, and utilization of adjuvant therapy in patients who are understaged. We conducted a retrospective review of NCDB patients diagnosed with clinical early stage gastric adenocarcinoma (cT1-2N0M0) between 2004 and 2016. Patients not undergoing upfront gastrectomy or with missing pathologic staging were excluded. Patients were classified as accurately staged, inaccurately staged with receipt of adjuvant therapy (IS+), and inaccurately staged with no receipt of adjuvant therapy (IS−). Logistic regression was utilized to assess the impact of factors on CS accuracy and receipt of adjuvant therapies. Kaplan–Meier and Cox proportional hazard methods were used for survival analysis. Approximately 40% of patients were inaccurately staged (IS). cT2, moderately/poorly differentiated, and site-overlapping tumors were associated with increased likelihood of being IS. Treatment at an academic facility was associated with decreased likelihood of understaging. Only 54% of patients who were IS received adjuvant therapy. Accurate CS of gastric cancer remains inadequate. Understaging is associated with detrimental effects on receiving guideline-concordant care and, possibly, patient outcomes. Targeted interventions reducing the proportion of understaged patients and ensuring receipt of appropriate therapy is needed to optimize outcomes. Patients with high-risk disease that are frequently understaged may benefit from selective neoadjuvant therapy. Centralization of gastric cancer care may also be a key strategy in improving receipt of guideline-concordant therapies.
- Published
- 2021
48. Role of Multidisciplinary Care in the Management of Hepatocellular Carcinoma
- Author
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Saleh A. Alqahtani, Adam C. Yopp, Amit G. Singal, and Kia Byrd
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medicine.medical_specialty ,Carcinoma, Hepatocellular ,Hepatology ,business.industry ,Liver Neoplasms ,Treatment options ,Multimodal therapy ,medicine.disease ,digestive system diseases ,Optimal management ,Review article ,Clinical Practice ,03 medical and health sciences ,0302 clinical medicine ,Multidisciplinary approach ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,medicine ,Overall survival ,Humans ,030211 gastroenterology & hepatology ,Intensive care medicine ,business - Abstract
Despite advances in treatment options for hepatocellular carcinoma (HCC), 5-year survival for HCC remains below 20%. This poor survival is multifactorial but is partly related to underuse of curative treatment in clinical practice. In light of growing treatment options, delivered by different types of providers, optimal management requires input from multiple specialties. A multidisciplinary approach has been evolving over the past couple of decades, bringing different specialists together to develop a therapeutic plan to treat and manage HCC, which significantly increases timely guideline-concordant treatment and improves overall survival. The present review attempts to highlight the need for such a multimodal approach by providing insights on its potential structure and impact on the various aspects of HCC management.
- Published
- 2021
49. Social vulnerability and survival in GI cancers
- Author
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Gilbert Zvikomborero Murimwa, Jennie Meier, Mithin Nehrubabu, Adam C. Yopp, Herbert J. Zeh, and Patricio M. Polanco
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Cancer Research ,Oncology - Abstract
787 Background: Social vulnerability is a federal metric used to assess a community’s resilience in facing external stressors from disease or disaster. The social vulnerability index (SVI) includes 15 social factors obtained at the census tract level within counties and ranks them along 4 themes – socioeconomic status, household composition and disability, minority status & language, and housing/transportation. Social vulnerability has never been explored at the census tract level in any malignancy and the Texas cancer registry provides granular detail at both the patient and census block group level not available in national datasets. We sought to characterize the relationship between social vulnerability and survival in gastrointestinal cancers, as well as its potential to identify themes for focused interventions to mitigate disparities. Methods: We retrospectively reviewed 196,651 patients with colorectal (CRC), gastric (GC), pancreatic (PDAC), and hepatocellular cancer (HCC) from the Texas Cancer Registry from 2004-2019. We analyzed patient demographics, social vulnerability (SVI), individual poverty index (PI), and clinicopathologic factors to understand their impact on survival at 2 years. Unadjusted and covariable-adjusted cox proportional hazards were used for survival analysis. Values were considered significant at pth percentile for the minority/language theme. At 2 years, individual poverty at 5-9%, 10-19%, and >20% of the federal poverty line (HR 1.06, 95%CI 1.03 - 1.09; HR 1.09, 95%CI 1.06 - 1.12; HR 1.13, 95%CI 1.10 - 1.17) was associated with increased risk of death. Medicaid as primary insurance, (HR 1.41, 95%CI 1.36 - 1.47), SVI socioeconomic status (HR 1.18, 95%CI 1.13 - 1.24), and household composition themes (HR 1.06, 95%CI 1.02 - 1.10) also associated with increased likelihood of death at 2 years. Notably, the minority theme was associated with improved survival (HR 0.85, 95%CI 0.82 - 0.89). Conclusions: Across four GI cancers, social vulnerability and poverty independently predicted survival at 2 years. Among SVI themes, socioeconomic status was the strongest predictor of worse survival, and the minority theme was associated with improved survival, potentially reflecting the Hispanic paradox. These findings suggest that the SVI may be used as a tool for identifying where resources can be targeted at a local level to mediate the survival disparity for vulnerable populations with GI malignancies.
- Published
- 2023
50. Hospital variation in use of prophylactic drains following hepatectomy
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Ryan P. Merkow, Mark E. Cohen, Brian C. Brajcich, Adam C. Yopp, Clifford Y. Ko, Karl Y. Bilimoria, Ryan J. Ellis, and Michael I. D’Angelica
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medicine.medical_specialty ,Hospital practice ,medicine.medical_treatment ,030230 surgery ,Logistic regression ,Article ,03 medical and health sciences ,Postoperative Complications ,0302 clinical medicine ,Open Resection ,medicine ,Hepatectomy ,Humans ,Aged ,Retrospective Studies ,Hepatology ,business.industry ,Gastroenterology ,Retrospective cohort study ,Bowel resection ,Odds ratio ,Hospitals ,Surgery ,030220 oncology & carcinogenesis ,Concomitant ,Drainage ,business - Abstract
BACKGROUND: Prophylactic drainage following hepatectomy is frequently performed despite evidence that drainage is unnecessary. It is unknown to what extent drain use is influenced by hospital practice patterns. The objectives of this study were to identify factors associated with the use of prophylactic drains following hepatectomy and assess hospital variation in drain use. METHODS: Retrospective cohort study of patients following hepatectomy without concomitant bowel resection or biliary reconstruction from the ACS NSQIP Hepatectomy Targeted Dataset. Factors associated with the use of prophylactic drains were identified using multivariable logistic regression and hospital-level variation in drain use was assessed. RESULTS: Analysis included 10,530 patients at 130 hospitals. Overall, 42.3% of patients had a prophylactic drain placed following hepatectomy. Patients were more likely to receive prophylactic drains if they were ≥65 years old (adjusted odds ratio [aOR]: 1.34, 95%CI: 1.16–1.56), underwent major hepatectomy (aOR: 1.42, 95%CI 1.15–1.74), or had an open resection (aOR 1.94, 95%CI 1.49–2.53). There was notable hospital variability in drain use (range: 0% to 100% of patients), and 77.5% of measured variation in drain placement was at the hospital level. CONCLUSION: Prophylactic drains are commonly placed in both major and minor hepatectomy. While some patient factors are associated with drain use, hospital-specific patterns appear to be a major driver and represent a target for improvement.
- Published
- 2020
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