BackgroundRegulatory T cells (Tregs) are highly prevalent in tumor tissue and can suppress effective anti-tumor immune responses. However, the source of the increased tumor-infiltrating Tregs and their contribution to cancer progression remain poorly understood.Methodology/Principal FindingWe here investigated the frequency, phenotype and trafficking property of Tregs and their prognostic value in patients with hepatocellular carcinoma (HCC). Our results showed that FoxP3+ Tregs highly aggregated and were in an activated phenotype (CD69+HLA-DRhigh) in the tumor site, where they can suppress the proliferation and INF-γ secretion of CD4+CD25− T cells. These tumor-infiltrating Tregs could be selectively recruited though CCR6-CCL20 axis as illustrated by (a) high expression of CCR6 on circulating Tregs and their selective migration to CCR6 ligand CCL20, and (b) correlation of distribution and expression between tumor-infiltrating Tregs and intratumoral CCL20. In addition, we found that the number of tumor-infiltrating Tregs was associated with cirrhosis background (P = 0.011) and tumor differentiation (P = 0.003), and was an independent prognostic factor for overall survival (HR = 2.408, P = 0.013) and disease-free survival (HR = 2.204, P = 0.041). The increased tumor-infiltrating Tregs predicted poorer prognosis in HCC patients.ConclusionsThe CCL20-CCR6 axis mediates the migration of circulating Tregs into tumor microenvironment, which in turn results in tumor progression and poor prognosis in HCC patients. Thus, blocking CCL20-CCR6 axis-mediated Treg migration may be a novel therapeutic target for HCC.

Tumor-infiltrating lymphocytes (TILs) represent the host immune response to cancer. CD8(+) cytotoxic T cells (CTLs) have a central role in the elimination of tumors, while regulatory T cells (Tregs) can suppress the immune reaction. The aim of this study was to investigate the prognostic value of TILs, especially Tregs and CTLs, in hepatocellular carcinoma (HCC) patients after resection. CD3(+), CD4(+), CD8(+), and FoxP3(+) TILs were assessed by immunohistochemistry in tumor tissue from 141 randomly selected HCC patients. Prognostic effects of low- or high-density TIL subsets were evaluated by Kaplan-Meier and Cox regression analysis using the median values as cutoff. The density of intratumoral Tregs (P = 0.040) and peritumoral CTLs (P = 0.004) were an independent factor for overall survival (OS), but not for disease-free survival (DFS). The density of CD3(+) and CD4(+) TILs, and the prevalence of Tregs and CTLs were associated with neither OS nor DFS. The presence of low intratumoral Tregs with high intratumoral CTLs was a negative independent prognostic factor for OS (P = 0.001), while that of low intratumoral Tregs and low peritumoral CTLs independently correlated with improved DFS (P = 0.008). Moreover, the combined analysis of Tregs and CTLs displayed better prognostic performances than any of them alone. Additionally, higher density of intratumoral Tregs correlated with both the presence of liver cirrhosis (P = 0.025) and increased tumor size (P = 0.050). Tregs within tumor environment are promising prognostic parameters for HCC patients, and their combination with CTLs can predict prognosis more effectively.

Background/Purpose: The liver has a remarkable capacity to regenerate after injury or resection. The aim of this review is to outline the mechanisms and factors affecting liver regeneration after liver transplantation. Methods: Relevant studies were reviewed using Medline, PubMed and Springer databases. Results: A variety of cytokines (such as interleukin-6 and tumor necrosis factor-α), growth factors (like hepatocyte growth factor and transforming growth factor-α) and cells are involved in liver regeneration. Several factors affect liver regeneration after transplantation such as ischemic injury, graft size, immunosuppression, steatosis, donor age and viral hepatitis. Conclusion: Liver regeneration has been studied for many years. However, further research is essential to reveal the complex processes affecting liver regeneration, which may provide novel strategies in the management of liver transplantation recipients and donors.

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Background: Laparoscopic cholecystectomy is the most commonly performed operation of the digestive tract. )It is considered as the gold standard treatment for cholelithiasis. Aim: To evaluate the outcome of it regarding length of hospital stay, complications, morbidity and mortality at a secondary hospital. Methods: Data of 492 patients who underwent laparoscopic cholecystectomy were retrospectively reviewed. Patients’ demographics, co-morbid diseases, previous abdominal surgery, conversion to open cholecystectomy, operative time, intra and postoperative complications, and hospital stay were collected and analyzed from patients’ files. Results: Out of 492 patients, 386 (78.5%) were females and 106 (21.5%) males. The mean age of the patients was 49.35±8.68 years. Mean operative time was 65.94±11.52 min. Twenty-four cases (4.9%) were converted to open surgery, four due to obscure anatomy (0.8%), 11 due to difficult dissection in Calot’s triangle (2.2%) and nine by bleeding (1.8%). Twelve (2.4%) cases had biliary leakage, seven (1.4%) due to partial tear in common bile duct, the other five due to slipped cystic duct stables. Mean hospital stay was 2.6±1.5 days. Twenty-one (4.3%) developed wound infection. Port site hernia was detected in nine (1.8%) patients. There was no cases of bowel injury or spilled gallstones. There was no mortality recorded in this series. Conclusions: Laparoscopic cholecystectomy is a safe and effective line for management of gallstone disease that can be performed with acceptable morbidity at a secondary hospital.

Exogenous administration of T3 significantly improved liver regeneration after pLT, and therefore it may represent a promising strategy to improve the clinical outcome after living donor liver transplantation in the future.