Jeffery Chakedis

Role of exosomes in treatment of hepatocellular carcinoma

Exosomes are nanovesicles that may play a role in intercellular communication by acting as carriers of functional contents such as proteins, lipids, RNA molecules and circulating DNA from donor to recipient cells. In addition, exosomes may play a potential role in immunosurveillance and tumor pathogenesis and progression. Recently, research has increasingly focused on the role of exosomes in hepatocellular carcinoma (HCC), the most common primary liver malignancy. We herein review data on emerging experimental and clinical studies focused on the role of exosomes in the pathogenesis, diagnosis, progression and chemotherapy response of patients with HCC. Beyond their diagnostic value in HCC, exosomes are involved in different mechanisms of HCC tumor pathogenesis and progression including angiogenesis and immune escape. Moreover, exosomes have been demonstrated to change the tumor microenvironment to a less tolerogenic state, favoring immune response and tumor suppression. These results underline a practical and potentially feasible role of exosomes in the treatment of patients with HCC, both as a target and a vehicle for drug design. Future studies will need to further elucidate the exact role and reliability of exosomes as screening, diagnostic and treatment targets in patients with HCC.

Liver transplantation for unresectable colorectal liver metastases: A systematic review

The use of liver transplantation (LT) for liver metastases attempted in the early 1990s was associated with poor perioperative outcomes and unacceptably low overall survival. Recently, there has been renewed interest in LT as a treatment option for colorectal liver metastases (CLM) in countries where organ supply is high. To date, no meticulous analysis about the efficacy, safety and outcomes of LT in CLM patients has been published. We present the first systematic review on the subject.

Early versus late recurrence of intrahepatic cholangiocarcinoma after resection with curative intent

The objective of this study was to investigate the characteristics, treatment and prognosis of early versus late recurrence of intrahepatic cholangiocarcinoma (ICC) after hepatic resection.

Postoperative Abdominal Adhesions: Clinical Significance and Advances in Prevention and Management

Postoperative adhesions remain one of the more challenging issues in surgical practice. Although peritoneal adhesions occur after every abdominal operation, the density, time interval to develop symptoms, and clinical presentation are highly variable with no predictable patterns. Numerous studies have investigated the pathophysiology of postoperative adhesions both in vitro and in vivo. Factors such as type and location of adhesions, as well as timing and recurrence of adhesive obstruction remain unpredictable and poorly understood. Although the majority of postoperative adhesions are clinically silent, the consequences of adhesion formation can represent a lifelong problem including chronic abdominal pain, recurrent intestinal obstruction requiring multiple hospitalizations, and infertility. Moreover, adhesive disease can become a chronic medical condition with significant morbidity and no effective therapy. Despite recent advances in surgical techniques, there is no reliable strategy to manage postoperative adhesions. We herein review the pathophysiology and clinical significance of postoperative adhesions while highlighting current techniques of prevention and treatment.

Cohort Contributions to Race- and Gender-Specific Trends in the Incidence of Hepatocellular Carcinoma in the USA

IntroductionIncreasing incidence of lifelong obesity and associated nonalcoholic steatohepatitis in younger birth cohorts may have contributed to growing incidence of hepatocellular carcinoma (HCC) in the USA. Yet, the contribution of cohort effects to trends in HCC incidence is unclear.MethodsUsing data from the Surveillance, Epidemiology, and End Results (SEER) program 1973–2013, race- and gender-specific trends in HCC incidence in the USA were decomposed using age-period-cohort (APC) modeling.ResultsAmong SEER registry sites included in the analysis, there were 25,532 cases of HCC diagnosed including 15,867 (62%) White males, 3541 (14%) Black males, 5009 (20%) White females, and 1115 (4%) Black females. HCC incidence increases across periods, especially among men. Underlying this increase, APC models found significant cohort effects among White men, White women, and Black men, with rapid growth in HCC risk among cohorts born after 1940. A similar cohort trend among Black women did not reach statistical significance when compared to an age-period model.ConclusionsCohort-specific trends have significantly contributed to increasing HCC incidence in recent decades. The rapid increase in HCC risk among younger cohorts suggests that the incidence of HCC will continue increasing in the near future.

The impact of a malignant diagnosis on the pattern and outcome of readmission after liver and pancreatic surgery: An analysis of the nationwide readmissions database

Reducing readmissions is an important quality improvement metric. We sought to investigate patterns of 90‐day readmission after hepato‐pancreatic (HP) procedures.

Circulating monocyte chemoattractant protein-1 (MCP-1) is associated with cachexia in treatment-naïve pancreatic cancer patients: A biomarker analysis in pancreatic adenocarcinoma-induced cachexia

Cancer‐associated wasting, termed cancer cachexia, has a profound effect on the morbidity and mortality of cancer patients but remains difficult to recognize and diagnose. While increases in circulating levels of a number of inflammatory cytokines have been associated with cancer cachexia, these associations were generally made in patients with advanced disease and thus may be associated with disease progression rather than directly with the cachexia syndrome. Thus, we sought to assess potential biomarkers of cancer‐induced cachexia in patients with earlier stages of disease.

Lymphadenectomy for Intrahepatic Cholangiocarcinoma: Has Nodal Evaluation Been Increasingly Adopted by Surgeons over Time?A National Database Analysis

BackgroundSurgical management of intrahepatic cholangiocarcinoma routinely includes resection of the hepatic parenchyma, yet the role of lymphadenectomy (LND) is more controversial. The objective of the current study was to define overall utilization, as well as temporal trends, in the utilization of LND among patients undergoing curative-intent hepatectomy for ICC using a nationwide database.Materials and MethodsOne thousand four hundred ninety-six patients who underwent curative-intent resection for ICC were identified using the SEER database from 2000 to 2013. The utilization of LND was assessed over time and by geographic region. LND utilization and the incidence of lymph node metastasis (LNM) were evaluated relative to AJCC T categories.ResultsAt the time of surgery, slightly over one-half of patients (n = 784, 52.4%) had at least one LN evaluated. Specifically, 613 (41.0%) patients had 1–5 LNs evaluated, whereas 171 (11.4%) patients had ≥ 6 LNs evaluated. The proportion of patients who had at least one LN evaluated at the time of surgery did not change with time (2000–2004: 50.5% vs. 2005–2009: 52.0% vs. 2010–2013: 53.7%) (p = 0.636). In contrast, the proportion of patients who had ≥ 6 LNs examined did increase (2000–2004: 6.9% vs. 2005–2009: 10.6% vs. 2009–2013: 14.3%) (p = 0.003). The risk of LNM was higher among patients with advanced T category tumors (Referent T1; T2a: OR 4.2, 95% CI 2.0–8.8, p < 0.001; T2b: OR 2.4, 95% CI 1.1–4.9, p = 0.018; T3: OR 3.6, 95% CI 1.6–7.9, p = 0.001; T4: OR 2.2, 95% CI 1.0–4.9, p = 0.049). In addition, the portion of patients with LNM varied among the different T categories (T1, 23.2%, T2a, 55.3%, T2b, 42.0%, T3, 51.4%, and T4, 39.5%; p = 0.001).ConclusionsUtilization of LND in the surgical management of ICC across the USA remained relatively low and did not change over the last decade. Selective utilization of LND may be problematic as T-stage was not a reliable predictor of nodal status with almost a quarter of patients with early stage disease having LNM.

Exosomes in Pancreatic Cancer: from Early Detection to Treatment

BackgroundPancreatic cancer (PC) remains one of the most fatal forms of cancer worldwide with incidence nearly equal to mortality. This is often attributed to the fact that diagnosis is often not made until later disease stages when treatment proves difficult. Efforts have been made to reduce the mortality of PC through improvements in early screening techniques and treatments of late-stage disease. Exosomes, small extracellular vesicles involved in cellular communication, have shown promise in helping understand PC disease biology.MethodsIn this review, we discuss current studies of the role of exosomes in PC physiology, and their potential use as diagnostic and treatment tools.ResultsExosomes have a role in diagnosing pancreatic cancer and in understanding tumor biology including migration, proliferation, chemoresistance, immunosuppression, cachexia and diabetes, and have a potential role in therapy for pancreatic cancer.ConclusionsExosomal analysis is beneficial in demonstrating mechanisms behind PC growth and metastasis, immunosuppression, drug resistance, and paraneoplastic conditions. Furthermore, the use of exosomes can be beneficial in detecting early-stage PC and exosomes have potential applications as therapeutic targets.

Management, outcomes, and prognostic factors of ruptured hepatocellular carcinoma: A systematic review.

Ruptured hepatocellular (rHCC) is a rare but life‐threatening presentation that often requires acute intervention. In this systematic review we identified 67 eligible studies reporting on 4941 patients with rHCC. Here we present the treatment approaches for the management of rHCC both in the acute setting with regards to management of hemorrhage, as well long‐term with regards to oncological treatment.