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Defining the Minimal and Optimal Thresholds for Lymph Node Resection and Examination for Intraductal Papillary Mucinous Neoplasm Derived Pancreatic Cancer: A Multicenter Retrospective Analysis

Habib, Joseph R; Rompen, Ingmar F; Kaslow, Sarah R; Grewal, Mahip; Andel, Paul C M; Zhang, Shuang; Hewitt, D Brock; Cohen, Steven M; van Santvoort, Hjalmar C; Besselink, Marc G; Molenaar, I Quintus; He, Jin; Wolfgang, Christopher L; Javed, Ammar A; Daamen, Lois A
OBJECTIVE:To establish minimal and optimal lymphadenectomy thresholds for intraductal papillary mucinous neoplasm (IPMN)-derived pancreatic ductal adenocarcinoma (PDAC) and evaluate their prognostic value. BACKGROUND:Current guidelines recommend a minimum of 12-15 lymph nodes (LNs) in PDAC. This is largely based on pancreatic intraepithelial neoplasia (PanIN)-derived PDAC, a biologically distinct entity from IPMN-derived PDAC. METHODS:Multicenter retrospective study including consecutive patients undergoing upfront surgery for IPMN-derived PDAC was conducted. The minimum cut-off for lymphadenectomy was defined as the maximum number of LNs where a significant node positivity difference was observed. Maximally selected log-rank statistic was used to derive the optimal lymphadenectomy cut-off (maximize survival). Kaplan-Meier curves and log-rank tests were used to analyze overall survival (OS) and recurrence-free survival (RFS). Multivariable Cox-regression was used to determine hazard ratios (HR) with 95% confidence intervals (95%CI). RESULTS:In 341 patients with resected IPMN-derived PDAC, the minimum number of LNs needed to ensure accurate nodal staging was 10 (P=0.040), whereas ≥20 LNs was the optimal number associated with improved OS (80.3 vs. 37.2 mo, P<0.001). Optimal lymphadenectomy was associated with improved OS [HR:0.57 (95%CI 0.39-0.83)] and RFS [HR:0.70 (95%CI 0.51-0.97)] on multivariable Cox-regression. On sub-analysis the optimal lymphadenectomy cut-offs for pancreatoduodenectomy, distal pancreatectomy, and total pancreatectomy were 20 (P<0.001), 23 (P=0.160), and 25 (P=0.008). CONCLUSION/CONCLUSIONS:In IPMN-derived PDAC, lymphadenectomy with at least 10 lymph nodes mitigates under-staging, and at least 20 lymph nodes is associated with the improved survival. Specifically, for pancreatoduodenectomy and total pancreatectomy, 20 and 25 lymph nodes were the optimal cut-offs.
PMCID:11470133
PMID: 38606874
ISSN: 1528-1140
CID: 5725942

Deep Learning Applications in Pancreatic Cancer

Patel, Hardik; Zanos, Theodoros; Hewitt, D Brock
Pancreatic cancer is one of the most lethal gastrointestinal malignancies. Despite advances in cross-sectional imaging, chemotherapy, radiation therapy, and surgical techniques, the 5-year overall survival is only 12%. With the advent and rapid adoption of AI across all industries, we present a review of applications of DL in the care of patients diagnosed with PC. A review of different DL techniques with applications across diagnosis, management, and monitoring is presented across the different pathological subtypes of pancreatic cancer. This systematic review highlights AI as an emerging technology in the care of patients with pancreatic cancer.
PMCID:10814475
PMID: 38275877
ISSN: 2072-6694
CID: 5625382

Association between surgical delay and outcomes among patients with invasive cutaneous melanoma

Hewitt, D Brock; Beane, Joal D; Grignol, Valerie P; Contreras, Carlo M
BACKGROUND:The relationship between surgical delay and outcomes for patients with cutaneous melanoma is understudied. The objectives of this study were to determine the impact of surgical delay on regional nodal involvement and mortality in patients with cutaneous melanoma. METHODS:Retrospective study of patients diagnosed with clinically node-negative invasive cutaneous melanoma from 2004 to 2018. Outcomes included regional lymph node disease and overall survival. Multivariable logistic regression and Cox proportional-hazards models were constructed to adjust for pertinent clinical factors. RESULTS:Of 423,001 patients, 21.8% experienced a surgical delay (≥45 days). These patients were more likely to have nodal involvement (OR1.09; P = 0.01). Surgical delay (HR1.14; P < 0.001), Black race (HR1.34; P = 0.002), and Medicaid (HR1.92; P < 0.001) were associated with lower survival. Patients treated at academic/research (HR0.87; P < 0.001) or integrated network cancer programs (HR0.89; P = 0.001) had improve survival. CONCLUSIONS:Surgical delay was frequent and resulted in higher rates of lymph node involvement and decreased overall survival.
PMID: 37142517
ISSN: 1879-1883
CID: 5544942

Racial and Ethnic Disparities in Synchronous and Metachronous Bilateral Breast Cancer

Hewitt, D Brock; Li, Yaming; Bhattacharyya, Oindrila; Fisher, James L; Stover, Daniel; Obeng-Gyasi, Samilia
INTRODUCTION/BACKGROUND:Significant racial and ethnic disparities exist in breast cancer treatment and survival. However, studies characterizing these disparities among patients developing bilateral breast cancers (BBC) are lacking. The purpose of this study is to understand the association between race and ethnicity, sociodemographic factors, clinical variables, treatment, and mortality in patients with BBC--synchronous bilateral breast cancer (sBBC) or metachronous bilateral breast cancer (mBBC). METHODS:Patients diagnosed with mBBC or sBBC in the Surveillance, Epidemiology, and End Results program between 2010 and 2016 were examined. sBBC was defined as contralateral breast cancer <1 year after the initial cancer diagnosis, and mBBC was contralateral cancer ≥1 year. Univariable analysis examined sociodemographic, clinical, and treatment variables. Kaplan-Meier curves and Cox regression models evaluated disease-specific mortality. RESULTS:Of the 11,493 patients that met inclusion criteria, 9575 (83.3%) had sBBC, and 1918 (16.7%) had mBBC. There were significant racial and ethnic differences in stage, tumor subtype, surgical management, and chemotherapy within sBBC and mBBC groups. On adjusted multivariate analysis of all BBC patients, Black race (HR 1.42; 95%CI 1.11-1.80; p<0.005; Ref White) was associated with a higher disease-specific mortality. Conversely, patients with mBBC had a 25% relative risk reduction in disease-specific mortality (HR 0.75; 95%CI 0.61-0.92; p<0.01) compared to sBBC. Subset analysis suggested Black Race modified the effect of sBBC on mortality (p<0.0001). CONCLUSIONS:Among patients with BBC, there are racial and ethnic disparities in clinical characteristics, treatment, and mortality. Future studies should focus on strategies to reduce these disparities.
PMID: 35386052
ISSN: 2196-8837
CID: 5233252

Invited commentary for the article "Evaluation of local recurrence after pancreaticoduodenectomy for borderline resectable pancreatic head cancer with neoadjuvant chemotherapy: Can the resection level change after chemotherapy?" [Editorial]

Hewitt, D Brock; Wolfgang, Christopher L
PMID: 36854642
ISSN: 1532-7361
CID: 5448472

Diagnosis and management of choledochal cysts

Brown, Zachary J; Baghdadi, Azarakhsh; Kamel, Ihab; Labiner, Hanna E; Hewitt, D Brock; Pawlik, Timothy M
BACKGROUND:Choledochal cysts (CCs) are rare cystic dilatations of the intrahepatic and/or extrahepatic bile ducts. We review the pathophysiology, diagnosis, and management of CCs. METHODS:MEDLINE/PubMed and Web of Science databases were queried for "choledochal cyst", "bile duct cyst", "choledochocele", and "Caroli disease". Data were synthesized and systematically reviewed. RESULTS:Classified according to the Todani Classification, CCs are generally believed to arise secondary to reflux of pancreatic enzymes into the biliary tree due to anomalous pancreaticobiliary duct union. Complications of CCs include abdominal pain, jaundice, cystolithiasis, cholecystitis, pancreatitis, liver abscess, liver cirrhosis and malignant transformation (3-7.5%). Radiological and endoscopic imaging is the cornerstone of CC diagnosis and full delineation of cyst anatomy is imperative for proper management. Management is generally guided by cyst classification with complete cyst excision necessary for CCs with high potential of malignant transformation such as types I and IV. 5-year overall survival after choledochal cyst excision is 95.5%. CONCLUSION:Most CCs should undergo surgical intervention to mitigate the risk of cyst related complications such as cholangitis and malignant transformation.
PMID: 36257874
ISSN: 1477-2574
CID: 5444452

The Role of Biomarkers in the Management of Colorectal Liver Metastases

Hewitt, Daniel Brock; Brown, Zachary J; Pawlik, Timothy M
Surgical management combined with improved systemic therapies have extended 5-year overall survival beyond 50% among patients with colorectal liver metastases (CRLM). Furthermore, a multitude of liver-directed therapies has improved local disease control for patients with unresectable CRLM. Unfortunately, a significant portion of patients treated with curative-intent hepatectomy develops disease recurrence. Traditional markers fail to risk-stratify and prognosticate patients with CRLM appropriately. Over the last few decades, advances in molecular sequencing technology have greatly expanded our knowledge of the pathophysiology and tumor microenvironment characteristics of CRLM. These investigations have revealed biomarkers with the potential to better inform management decisions in patients with CRLM. Actionable biomarkers such as RAS and BRAF mutations, microsatellite instability/mismatch repair status, and tumor mutational burden have been incorporated into national and societal guidelines. Other biomarkers, including circulating tumor DNA and radiomic features, are under active investigation to evaluate their clinical utility. Given the plethora of therapeutic modalities and lack of evidence on timing and sequence, reliable biomarkers are needed to assist clinicians with the development of patient-tailored management plans. In this review, we discuss the current evidence regarding biomarkers for patients with CRLM.
PMCID:9559307
PMID: 36230522
ISSN: 2072-6694
CID: 5444442

Role of genetic testing in hepatic, pancreatic, and biliary cancers

Hewitt, D Brock; Aziz, Hassan; Brown, Zachary J; Pawlik, Timothy M
Hepatic, pancreatic, and biliary (HPB) cancers, including hepatocellular carcinoma (HCC), pancreatic ductal adenocarcinoma (PDAC), and cholangiocarcinoma (CCA) cause a disproportionate amount of the global cancer-related mortality. Despite advances in surgical technique and improved systemic therapies, overall 5-year survival remains dismal, especially for patients with pancreatic and biliary cancer. Historically, systemic therapies for patients with HPB cancers were administered in a "one-size-fits-all" approach due to limited reliable data on efficacy for specific patient populations. However, recent advances in genetic testing techniques have greatly improved our understanding of HPB oncogenesis, shedding light on specific genetic mutations responsible for progression from physiologic cellular regulation to uninhibited cellular replication and invasive cancer. Investigations into the oncogenesis of HPB cancers have revealed multiple actionable genetic variants, as well as increased susceptibilities to currently available systemic therapies. For example, patients with PDAC and a known BRCA mutation are more likely to benefit from FOLFIRINOX or gemcitabine plus cisplatin. While patients with CCA and a IDH1 mutation may benefit from ivosidenib. As a result, many national and societal guidelines now recommend some form of genetic testing in the workup of patients with HPB cancers. We herein review the role of genetic testing in these aggressive cancers including DNA sequencing techniques, clinically relevant mutations, therapeutic implications, and current clinical recommendations.
PMID: 36116416
ISSN: 1879-3320
CID: 5444392

Pancreatic ductal adenocarcinoma: Emerging therapeutic strategies

Osei-Bordom, Daniel C; Serifis, Nikolaos; Brown, Zachary J; Hewitt, D Brock; Lawal, Gbemisola; Sachdeva, Gagandeep; Cloonan, Daniel J; Pawlik, Timothy M
The seventh leading cause of cancer-related death globally, pancreatic ductal adenocarcinoma (PDAC) involves the exocrine pancreas and constitutes greater than 90% of all pancreatic cancers. Surgical resection in combination with systemic chemotherapy with or without radiation remains the mainstay of treatment and the only potentially curative treatment option. While there has been improvement in systemic chemotherapy, long-term survival among patients with PDAC remains poor. Improvement in the understanding of tumorigenesis, genetic mutations, the tumor microenvironment (TME), immunotherapies, as well as targeted therapies continued to drive advances in PDAC treatment. We herein review the TME, genetic landscape, as well as various metabolic pathways associated with PDAC tumorigenesis relative to emerging therapies.
PMID: 35830772
ISSN: 1879-3320
CID: 5444362

Socioeconomic Status and Gastric Cancer Surgical Outcomes: A National Cancer Database Study

Lamm, Ryan; Hewitt, D Brock; Li, Michael; Powell, Adam C; Berger, Adam C
INTRODUCTION:Gastric cancer (GC) is the third leading cause of cancer-related death worldwide. Surgical resection is the gold standard of treatment. In the United States, race and socioeconomic status are associated with the diagnosis of GC; however, no studies have examined these as independent risk factors for surgical outcomes. Our study sought to investigate socioeconomic factors and GC surgical outcomes using a national cancer registry. METHODS:GC patients between 2004 and 2016 were identified using the National Cancer Database. Univariate and multivariate logistic regression was used to analyze associations between socioeconomic factors and 30-d mortality, 90-d mortality, and unplanned readmission rate. RESULTS:A total of 96,990 patients who received nonpalliative surgical treatment for GC were identified. When controlling for other clinical and socioeconomic factors, older age, male sex, higher comorbidities, larger tumor size, advanced stage disease, and inadequate resection were correlated with worse 30- and 90-d mortality. Additionally, 30-d and 90-d mortality was significantly lower when the patient's income (odds ratio [OR] = 0.77 and OR = 0.43, respectively, for >$63,333/y versus <$40.227/y) and the percentage of residents with a high school degree in their zip code (OR = 0.69 and OR = 0.52, respectively, for <6.3% no high school degree versus ≥ 17.6%) were higher. No significant disparate trends were identified in terms of race and insurance status or in unplanned readmissions on multivariate analysis. CONCLUSIONS:Lower income and the level of education at the place of residence were independently associated with higher 30-d and 90-d mortality in this study, highlighting the potential for a major socioeconomic disparity in this population.
PMID: 35320743
ISSN: 1095-8673
CID: 5233232