Faculty Bibliography

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.

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.

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.

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.

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.

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.

INTRODUCTION/UNASSIGNED:Hepatocellular carcinoma (HCC) is a major health problem worldwide with limited systemic therapy options. Since the approval of sorafenib in 2008, no systemic therapy has provided a sustained/robust/survival benefit for patients with advanced HCC until recently. Many initially promising therapies have been trialed, but survival outcomes remained stagnant. Knowledge concerning previous treatment failures may help inform future therapeutic approaches. AREA COVERED/UNASSIGNED:This article reviews recent advances in the treatment of HCC. Despite some recent success, many systemic and locoregional therapies have failed to produce significant improvements in outcome. These treatment failures are examined and insight into pathways for future success are discussed. EXPERT OPINION/UNASSIGNED:Combination atezolizumab and bevacizumab has changed the landscape of systemic treatment for patients with HCC when it became the first therapy after demonstrating improve outcomes over sorafenib. Clinical trials in patients with advanced HCC have inherent difficulty with challenges to determine if a patient's declining liver function is secondary to disease progression, worsening cirrhosis, or drug toxicity, which may skew results. As we gain more knowledge of underlying genetic alterations behind the pathophysiology of the development of HCC, molecular markers may be identified to assist in predicting which patients would respond to a specific therapy.

Cholangiocarcinoma (CCA) represents nearly 15% of all primary liver cancers and 2% of all cancer-related deaths worldwide. Perihilar cholangiocarcinoma (pCCA) accounts for 50-60% of all CCA. First described in 1965, pCCAs arise between the second-order bile ducts and the insertion of the cystic duct into the common bile duct. CCA typically has an insidious onset and commonly presents with advanced, unresectable disease. Complete surgical resection is technically challenging, as tumor proximity to the structures of the central liver often necessitates an extended hepatectomy to achieve negative margins. Intraoperative frozen section can aid in assuring negative margins and complete resection. Portal lymphadenectomy provides important prognostic and staging information. In specialized centers, vascular resection and reconstruction can be performed to achieve negative margins in appropriately selected patients. In addition, minimally invasive surgical techniques (e.g., robotic surgery) are safe, feasible, and provide equivalent short-term oncologic outcomes. Neoadjuvant chemoradiation therapy followed by liver transplantation provides a potentially curative option for patients with unresectable disease. New trials are needed to investigate novel chemotherapies, immunotherapies, and targeted therapies to better control systemic disease in the adjuvant setting and, potentially, downstage disease in the neoadjuvant setting.