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Background/Aim: Apolipoprotein E-deficient (Apoe(−/−)) mice develop atherosclerotic lesions that closely resemble metabolic syndrome in humans. We sought to investigate how rosuvastatin mitigates the atherosclerotic profile of Apoe(−/−) mice over time and its effects on certain inflammatory chemokines. Materials and Methods: Eighteen Apoe(−/−) mice were allocated into three groups of six mice each receiving: standard chow diet (SCD; control group); high-fat diet (HFD); and HFD and rosuvastatin at 5 mg/kg/d orally via gavage for 20 weeks. Analysis of aortic plaques and lipid deposition was conducted by means of en face Sudan IV staining and Oil Red O staining. Serum cholesterol, low-density lipoprotein, high-density lipoprotein, plasma glucose and triglyceride levels were determined at baseline and after 20 weeks of treatment. Serum interleukin 6 (IL6), C-C motif chemokine ligand 2 (CCL2) and tumor necrosis factor-α (TNFα) levels were measured by enzyme-linked immunosorbent assay at the time of euthanasia. Results: The lipidemic profile of Apoe(−/−) mice on HFD deteriorated over time. Apoe(−/−) mice on HFD developed atherosclerotic lesions over time. Sudan IV and Oil Red O-stained sections of the aorta revealed increased plaque formation and plaque lipid deposition in HFD-fed mice compared with SCD-fed mice and reduced plaque development in HFD-fed mice treated with rosuvastatin compared with mice not receiving statin treatment. Serum analysis revealed reduced metabolic parameters in HFD-fed mice on rosuvastatin compared with non-statin, HFD-fed mice. At the time of euthanasia, HFD-fed mice treated with rosuvastatin had significantly lower IL6 as well as CCL2 levels when compared with HFD-fed mice not receiving rosuvastatin. TNFα levels were comparable among all groups of mice, irrespective of treatment. IL6 and CCL2 positively correlated with the extent of atherosclerotic lesions and lipid deposition in atherosclerotic plaques. Conclusion: Serum IL6 and CCL2 levels might potentially be used as clinical markers of progression of atherosclerosis during statin treatment for hypercholesterolemia.

The impact of chronic kidney disease (CKD) on surgery is still not well defined. We sought to characterize the association of preoperative CKD with 30-day mortality after hepatic resection.Patients included in the American College of Surgeons (ACS) NSQIP who underwent hepatectomy between 2014 and 2018 were identified. Kidney function was stratified according to the "Kidney Disease: Improving Global Outcomes" (KDIGO) Classification: G1, normal/high function (estimated glomerular-filtration-rate ≥ 90 ml/min/1.73m2); G2-3, mild/moderate CKD (89-30 ml/min/1.73m2); G4-5, severe CKD (≤ 29 ml/min/1.73m2).Overall, 18,321 patients were included. Older patients (ie more than 70 years old) and those with serious medical comorbidities (ie American Society of Anesthesiologists [ASA] class 3) had an increased incidence of severe CKD (both p0.001). Patients with G2-3 and G4-5 CKD were more likely to have a prolonged length of stay and to experience postoperative complications (both p0.001). Adjusted odds of 30-day mortality increased with the worsening CKD (p = 0.03). The degree of CKD was able to stratify patients within the NSQIP risk calculator. Among patients who underwent major hepatectomy for primary cancer, the rate of 30-day mortality was 2-fold higher with G2-3 and G4-5 CKD vs normal kidney function (p = 0.03).The degree of CKD was related to the risk of complications and 30-day mortality after hepatectomy. CKD classification should be strongly considered in the preoperative risk estimation of these patients.

Dimitrios Papaconstantinou,1 Diamantis I Tsilimigras,2 Timothy M Pawlik2 1Third Department of Surgery, Attikon University Hospital, National and Kapodistrian University of Athens, Athens, Greece; 2Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio, USACorrespondence: Timothy M Pawlik, Department of Surgery, The Urban Meyer III and Shelley Meyer Chair for Cancer Research, The Ohio State University, Wexner Medical Center, 395 W. 12th Ave., Suite 670, Columbus, OH, USA, Tel +1 614 293 8701, Fax +1 614 293 4063, Email tim.pawlik@osumc.eduAbstract: Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related deaths worldwide with the incidence of recurrence being as high as 88% even among patients who have undergone curative-intent treatment. Despite improvements in overall survival, recurrence remains a challenge necessitating accurate reappraisal of patient and disease status. To that end, accurate staging of recurrent HCC is a necessity to provide better care for these patients. Risk factors for poor survival after HCC recurrence have been identified and include characteristics of the primary disease, such as tumor multifocality, large size (≥ 5 cm), macroscopic vascular or microscopic lymphovascular invasion, preoperative a-fetoprotein (AFP) levels, R0 resection, and the presence of impaired liver function. Close surveillance with imaging is warranted following curative-intent therapy, with magnetic resonance imaging (MRI) being the preferred approach to identify small, early recurrent HCCs. Treatment decisions at the time of recurrence involve ruling out extrahepatic disease and identifying candidates for potentially curative-intent repeat treatment options. Patients with recurrent disease are, however, very diverse in terms of tumor morphology and biologic behavior, as well as residual hepatic functional reserve. Patients with preserved liver function may benefit from repeat liver resection or ablation. Patients with recurrence within the Milan criteria may even be candidates for salvage liver transplantation, while multimodality treatment with combination of liver-directed therapies appears to enhance oncologic outcomes for individuals with advanced recurrent disease. A “one-size-fits-all” approach in staging recurrent HCC does not exist. Rather, individualized and evidence-based decision-making is necessary in order to optimize outcomes for patients with recurrent HCC.Keywords: hepatocellular carcinoma, recurrence, staging, treatment, classification

Nikolaos Serifis,1 Diamantis I Tsilimigras,2 Daniel J Cloonan,3 Timothy M Pawlik2 1Center for Transplantation Sciences, Massachusetts General Hospital, Boston, MA, USA; 2Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA; 3Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA, USACorrespondence: Diamantis I TsilimigrasDepartment of Surgery, The Ohio State University, Wexner Medical Center, 410 W 10th Avenue, Columbus, OH, 43210, USATel +1 215 987 9177Email diamantis.tsilimigras@osumc.eduAbstract: Intrahepatic cholangiocarcinoma (ICC) is one of the rarest and most aggressive types of cancer. The symptoms of ICC patients can be vague, leading to late diagnosis and dismal prognosis. In this review, we investigated the treatment options for ICC, as well as ways to overcome challenges in identifying and treating this disease. Imaging remains the gold standard to diagnose ICC. Patients are staged based on the tumor, nodes and metastases (TNM) staging system. Patients eligible for surgical resection should undergo surgery with curative intent with the goal of microscopically disease-free margins (R0 resection) along with lymphadenectomy. Minimal invasive surgery (MIS) and liver transplantation have recently been offered as possible ways to improve disease outcomes. ICC recurrence is relatively common and, thus, most patients will need to be treated with systemic therapy. Several clinical trials have recently investigated the use of neoadjuvant (NT) and adjuvant therapies for ICC. NT may offer an opportunity to downsize larger tumors and provide patients, initially ineligible for surgery, with an opportunity for resection. NT may also treat occult micro-metastatic disease, as well as define tumor biology prior to surgical resection, thereby decreasing the risk for early postoperative recurrence. Adjuvant systemic therapy may improve outcomes of patients with ICC following surgery. Ongoing clinical trials are investigating new targeted therapies that hold the hope of improving long-term outcomes of patients with ICC.Keywords: liver, intrahepatic cholangiocarcinoma, resection, outcomes