Faculty Bibliography

IMPORTANCE/UNASSIGNED:Hepatocellular carcinoma (HCC) is the sixth most common malignancy and fourth leading cause of cancer-related death worldwide. Recent advances in systemic and locoregional therapies have led to changes in many guidelines regarding systemic therapy, as well as the possibility to downstage patients to undergo resection. This review examines the advances in surgical and medical therapies relative to multidisciplinary treatment strategies for HCC. OBSERVATIONS/UNASSIGNED:HCC is a major health problem worldwide. The obesity epidemic has made nonalcoholic fatty liver disease a major risk factor for the development of HCC. Multiple societies, such as the American Association for the Study of Liver Diseases, the European Association for the Study of the Liver, the Asian Pacific Association for the Study of the Liver, and the National Comprehensive Cancer Network, provide guidelines for screening at-risk patients, as well as define staging systems to guide optimal treatment strategies. The Barcelona Clinic Liver Cancer staging system is widely accepted and has recently undergone updates with the introduction of new systemic therapies and stage migration. CONCLUSIONS AND RELEVANCE/UNASSIGNED:The treatment of patients with HCC should involve a multidisciplinary approach with collaboration among surgeons, medical oncologists, radiation oncologists, and interventional radiologists to provide optimal care. Treatment paradigms must consider both tumor and patient-related factors such as extent of liver disease, which is a main driver of morbidity and mortality. The advent of more effective systemic and locoregional therapies has prolonged survival among patients with advanced disease and allowed some patients to undergo surgical intervention who would otherwise have disease considered unresectable.

BACKGROUND:Fibrolamellar hepatocellular carcinoma (FL-HCC) is a rare disease and current efforts are focused on the prognosis and on the development of efficient and specific treatments. This study aimed to review the latest evidence regarding FL-HCC treatment and prognosis. METHODS:A systematic review of the literature over the past 10 years regarding FL-HCC, and meta-analysis of 1-, 3-, and 5-year overall survival (OS) comparing FL-HCC and conventional HCC were performed. RESULTS:Overall, 1567 articles were screened, of them 21 were selected for the systematic review, and 6 for meta-analysis. Twenty-one studies included a total of 2168 patients with FL-HCC, with a median age ranging from 11 to 56 years. The majority of patients underwent surgical resection or liver transplantation. After a median follow-up ranging from 24 to 58 months, 1-year OS was 67-100% and 5-year OS was 28-65%. A total of 743 patients with FL-HCC and 163,472 with conventional HCC were included in the meta-analysis. There was a significantly improved 1-, 3-, and 5-years OS in the FL-HCC group compared to the conventional HCC group, although high heterogeneity was found. When excluding population-based studies, and including 96 FL-HCC and 221 conventional HCC patients, the heterogeneity was low, and the meta-analysis showed a significantly longer 1-year OS in patients with FL-HCC than conventional HCC; however, there were no differences at 3- and 5-years OS. CONCLUSIONS:Surgical resection for FL-HCC is currently the only curative treatment available. FL-HCC is plagued by high-recurrence rates and poor long-term outcomes which may be related to the absence of specific treatment for advanced and recurrent disease.

BACKGROUND:This study aimed to develop a holistic risk score incorporating preoperative tumor, liver, nutritional, and inflammatory markers to predict overall survival (OS) after hepatectomy for hepatocellular carcinoma (HCC). METHODS:Patients who underwent curative-intent surgery for HCC between 2000 and 2020 were identified using an international multi-institutional database. Preoperative predictors associated with OS were selected and a prognostic risk score model (PreopScore) was developed and validated using cross-validation. RESULTS:A total of 1676 patients were included. On multivariable analysis, preoperative parameters associated with OS included α-feto protein (hazard ratio [HR]1.17, 95%CI 1.03-1.34), neutrophil-to-lymphocyte ratio (HR2.62, 95%CI 1.30-5.30), albumin (HR0.49, 95%CI 0.34-0.70), gamma-glutamyl transpeptidase (HR1.00, 95%CI 1.00-1.00), as well as vascular involvement (HR3.52, 95%CI 2.10-5.89) and tumor burden score (medium, HR3.49, 95%CI 1.62-7.58; high, HR3.21, 95%CI 1.40-7.35) on preoperative imaging. A weighted PreopScore was devised and made available online (https://yutaka-endo.shinyapps.io/PrepoScore_Shiny/). Patients with a PreopScore 0-2, 2-3.5, and >3.5 had incrementally worse 5-year OS of 85.8%, 70.7%, and 52.4%, respectively (p < 0.001). The c-index of the test and validation cohort were 0.75 and 0.71, respectively. The PreopScore outperformed individual parameters and previous HCC staging systems. DISCUSSION:The PreopScore can be used as a better guide to preoperatively identify patients and individualize pre-/post-operative strategies.

INTRODUCTION:Cholangiocarcinoma (CCA) is an uncommon malignancy originating from epithelial cells of the biliary tract. Regardless of the site of origin within the biliary tree, CCAs are generally aggressive with a poor survival. Surgical resection remains the only chance for cure, yet a majority of patients are not surgical candidates at presentation. Unfortunately, systemic therapies are often ineffective and complicated by side effects. As such, more effective targeted therapies are required in order to improve survival. AREA COVERED:have proven to have therapeutic benefit with an acceptable safety profile. However, patients often develop resistance rendering the therapy ineffective. EXPERT OPINION:may lead to a better understanding of the mechanisms of resistance. Thus, novel therapies may be developed to improve the efficacy of these therapies. Developing novel biomarkers may improve patient selection and further enhance effectiveness of targeted therapies.

PURPOSE/OBJECTIVE:To investigate recurrence patterns after surgery for intrahepatic cholangiocarcinoma (ICC) relative to lymph node status, tumor extension, tumor burden score (TBS), and adjuvant chemotherapy. METHODS:Patients who underwent curative-intent resection for ICC from 1990 to 2020 were enrolled from a multi-institutional database. The hazard function was applied to plot the hazard rates over time, with further stratification by T and N AJCC 8th edition categories, TBS, and adjuvant chemotherapy. RESULTS:A total of 1192 patients underwent curative-intent resection for ICC and 59.9% experienced recurrence. Overall, the peak of recurrence occurred at 6.6 months. Among patients with negative lymph nodes, the T4-category had a higher peak rate of recurrence (0.1199 at 10.2 months) compared with other T-categories, while high TBS had an earlier peak of recurrence (4.2 months) compared with lower TBS. Among patients with N1 disease, T2-T4 categories had multipeak patterns of recurrence with higher hazard rates during the first 3 years after surgery in comparison with T1-category, while patients with high TBS had an earlier (4.0 months) and higher hazard peak rate compared with lower TBS groups. The administration of adjuvant chemotherapy was associated with delayed hazard rates of recurrence for N1 (4 months) and NX (6 months) categories. DISCUSSION/CONCLUSIONS:The novel application of the hazard function to assess hazard rates and timing patterns of recurrence following resection for ICC demonstrated that recurrence varied based on T- and N-categories, as well as TBS. Hazard function-based recurrence data may be helpful to tailor counseling, surveillance, and adjuvant therapy recommendations.

BACKGROUND:Fibrolamellar hepatocellular carcinoma (FLC) is a rare malignancy that primarily affects patients in late adolescence and young adulthood. FLC tumors are characterized by their unique histologic features and a recently discovered genomic alteration, a chimeric fusion protein found in nearly all tumors. This review article provides the latest advancements in diagnosing, imaging, and managing FLC. STUDY DESIGN/METHODS:A comprehensive systematic review was performed using MEDLINE/PubMed and Web of Science databases, with the end of search date being July 1, 2022, regarding FLC diagnosis, imaging, and management. RESULTS:Surgical resection remains the mainstay of therapy offering a chance for cure; however, given the incidence of metastatic disease at diagnosis and high rates of distant relapse, systemic therapies remain a crucial component of disease control. Unfortunately, few systemic therapies have demonstrated proven benefits. Consequently, recent efforts have galvanized around single-institute or small consortia-based studies specifically focused on enrolling patients with FLC or using agents with a biologic rationale. CONCLUSIONS:FLC has unique demographic, radiologic, and pathologic features. The rarity of these tumors, coupled with the only recent acknowledgment of the genomic abnormality, has likely led to disease underrecognition and deprioritization of collaborative efforts to establish an evidence-based standard of care. Despite R0 resection, most patients experience recurrence. However, surgical resection is feasible for many recurrences and is associated with good survival. The role of chemotherapy is evolving, and further research is required to define its role in managing this disease.

BACKGROUND:Defining patterns and risk of recurrence can help inform surveillance strategies and patient counselling. We sought to characterize peak hazard rates (pHR) and peak time of recurrence among patients who underwent resection of hepatocellular carcinoma (HCC). METHODS:1434 patients who underwent curative-intent resection of HCC were identified from a multi-institutional database. Hazard, patterns, and peak rates of recurrence were characterized. RESULTS:The overall hazard of recurrence peaked at 2.4 months (pHR: 0.0384), yet varied markedly. The incidence of recurrence increased with Barcelona Clinic Liver Cancer (BCLC) stage 0 (29%), A (54%), and B (64%). While the hazard function curve for BCLC 0 patients was relatively flat (pHR: <0.0177), BCLC A patients recurred with a peak at 2.4 months (pHR: 0.0365). Patients with BCLC B had a bimodal recurrence with a peak rate at 4.2 months (pHR: 0.0565) and another at 22.8 months. The incidence of recurrence also varied according to AFP level (≤400 ng/mL: 52.6% vs. >400 ng/mL: 36.3%) and Tumor Burden Score (low: 73.7% vs. medium: 50.6% vs. high: 24.2%) (both p < 0.001). CONCLUSION:Recurrence hazard rates for HCC varied substantially relative to both time and intensity/peak rates. TBS and AFP markedly impacted patterns of hazard risk of recurrence.

BACKGROUND:The kidney is the most frequently injured component of the genitourinary system, accounting for 5% of all trauma cases. Several guidelines by different societies address the management of urological trauma. However, unanswered questions remain regarding optimal use of angioembolization in hemodynamically stable patients, indications for operative exploration of stable retroperitoneal hematomas and renal salvage techniques in the setting of hemodynamic instability, and imaging practices for patients undergoing non-operative management. We performed a systematic review, meta-analysis, and developed evidence-based recommendations to answer these questions in both blunt and penetrating renal trauma. METHODS:The working group formulated four population, intervention, comparator, outcome (PICO) questions regarding the following topics: (1) angioembolization (AE) usage in hemodynamically stable patients with evidence of ongoing bleeding; (2) surgical approach to stable zone II hematomas (exploration vs. no exploration) in hemodynamically unstable patients and (3) surgical technique (nephrectomy vs. kidney preservation) for expanding zone II hematomas in hemodynamically unstable patients; (4) frequency of repeat imaging (routine or symptom based) in high-grade traumatic renal injuries. A systematic review and meta-analysis of currently available evidence was performed. RevMan 5 (Cochran Collaboration) and GRADEpro (Grade Working Group) software were used. Recommendations were voted on by working group members and concurrence was obtained for each final recommendation. RESULTS:A total of 20 articles were identified and analyzed. Two prospective studies were encountered; the majority were retrospective, single-institution studies. Not all outcomes projected by PICO questions were reported in all studies. Meta-analysis was performed for all PICO questions except PICO 3 secondary to the discrepant patient populations included in those studies. PICO 1 had the greatest number of articles included in the meta-analysis with nine studies; yet, due to differences in study design, no critical outcomes emerged; similar differences among a smaller set of articles prevented observation of critical outcomes for PICO 4. Analyses of PICOs 2 and 3 favored a non-invasive or minimally invasive approach in-line with current international practice trends. CONCLUSION/CONCLUSIONS:In hemodynamically stable adult patients with clinical or radiographic evidence of ongoing bleeding, no recommendation could be made regarding the role of AE vs. observation. In hemodynamically unstable adult patients, we conditionally recommend no renal exploration vs. renal exploration in stable zone II hematomas. In hemodynamically unstable adult patients, we conditionally recommend kidney preserving techniques vs. nephrectomy in expanding zone II hematomas. No recommendation could be made for the optimal timing of repeat imaging in high grade renal injury. LEVEL OF EVIDENCE/METHODS:Guideline; systematic review, level III.

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.