Faculty Bibliography

PURPOSE/OBJECTIVE:Neoadjuvant therapy (NT) is increasingly utilized for patients with localized pancreatic ductal adenocarcinoma (PDAC). Patients with cancer have high information needs and the Internet has materialized as a leading source of information for many patients. Nevertheless, little is known about the availability, accessibility, quality, and readability of online information regarding NT for PDAC. METHODS:A search of online patient informational materials (PIMs) pertaining to NT for PDAC was conducted using a combination of common search engines and browsers. Two independent researchers evaluated the readability, quality, and availability of unique PIMs from the top 25 websites from each search using validated measures. RESULTS:Among the 130 websites retrieved, 46 (35.4%) unique PIMs focused on treatment of PDAC. Only 30 (23%) mentioned NT as a possible treatment option. Downstaging was the rationale for NT mentioned in the majority (90%) of websites. The mean quality and reliability of the 30 PIMs, assessed using the DISCERN instrument, was 3.3 ± 0.7, suggesting moderate quality/reliability. The mean readability score, assessed using the SMOG Grade tool, was 10.96 ± 1.49, which is equivalent to an 11th grade reading level. CONCLUSION/CONCLUSIONS:The low availability, poor readability, and moderate quality of online informational materials regarding NT for PDAC highlight the need for new patient-centered resources to educate patients and caregivers on an increasingly utilized treatment strategy for localized PDAC.

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: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.

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.

Pancreatic ductal adenocarcinoma is an aggressive malignancy that carries a poor prognosis because the majority of patients present with locally advanced or metastatic disease. However, even patients who are fortunate enough to present with resectable disease are often plagued by high recurrence rates. While adjuvant chemotherapy has been shown to decrease the risk of recurrence after surgery, post operative complications and poor performance status after surgery prevent up to 50% of patients from receiving it. Given the benefits of neoadjuvant therapy in patients with borderline resectable disease, it is understandable that neoadjuvant therapy has been steadily increasing in patients with resectable cancers as well. In this review paper, we highlight the rational and existing evidence of using neoadjuvant therapy in all patients with resectable pancreatic adenocarcinoma.

Platelets, the often-overlooked component of the immune system, have been shown to promote tumor growth. Non-alcoholic fatty liver disease (NAFLD) is a common disease in the Western world and rising risk for hepatocellular carcinoma (HCC). Unexpectedly, we observed that platelets can inhibit the growth of established HCC in NAFLD mice. Through pharmacological inhibition and genetic depletion of P2Y12 as well as in vivo transfusion of wild-type (WT) or CD40L^-/- platelets, we demonstrate that the anti-tumor function of platelets is mediated through P2Y12-dependent CD40L release, which leads to CD8⁺ T cell activation by the CD40 receptor. Unlike P2Y12 inhibition, blocking platelets with aspirin does not prevent platelet CD40L release nor accelerate HCC in NAFLD mice. Similar findings were observed in liver metastasis models. All together, our study reveals a complex role of platelets in tumor regulation. Anti-platelet treatment without inhibiting CD40L release could be considered for liver cancer patients with NAFLD.