KIF5A upregulation in hepatocellular carcinoma: A novel prognostic biomarker associated with unique tumor microenvironment status.

Liver hepatocellular carcinoma (LIHC) is one of the most common liver malignancies with high mortality and morbidity. Thus, it is crucial to identify potential biomarker that is capable of accurately predicting the prognosis and therapeutic response of LIHC. Kinesin family member 5A (KIF5A) is a microtubule-based motor protein involved in the transport of macromolecules such as organelle proteins in cells. Recent studies have illustrated that the high expression of KIF5A was related to poor prognosis of solid tumors, including bladder cancer, prostate cancer, and breast cancer. However, little is currently known concerning the clinical significance of KIF5A expression in LIHC. Herein, by adopting multi-omics bioinformatics analysis, we comprehensively uncovered the potential function and the predictive value of KIF5A in stratifying clinical features among patients with LIHC, for which a high KIF5A level predicted an unfavorable clinical outcome. Results from KIF5A-related network and enrichment analyses illustrated that KIF5A might involve in microtubule-based process, antigen processing and presentation of exogenous peptide antigen via MHC class II. Furthermore, immune infiltration and immune function analyses revealed upregulated KIF5A could predict a unique tumor microenvironment with more CD8+T cells and a higher level of anti-tumor immune response. Evidence provided by immunohistochemistry staining (IHC) further validated our findings at the protein level. Taken together, KIF5A might serve as a novel prognostic biomarker for predicting immunotherapy response and could be a potential target for anti-cancer strategies for LIHC.

Laparoscopic cholecystectomy in elderly patients: an evaluation of immunity.

OBJECTIVE: We sought to investigate the impact of laparoscopic cholecystectomy (LC) on the inflammatory response and immunological function of elderly patients compared with that on the younger ones. METHODS: Between June 2012 and June 2013, this prospective study investigated a total of 112 patients having the surgery of LC due to symptomatic cholelithiasis or polyps, among whom 52 were elderly patients with the age beyond 65 years old and the remaining 60 were younger than the age. Peripheral venous blood samples were taken from these patients prior to surgery and on post-operative days 1, 3 and 7, respectively. The perioperative clinical outcomes and immunological function results were analyzed and compared between the two groups divided by age. RESULTS: The demographics of the two groups did not differ except for the age. Surgical trauma seemed more serious for elderly patients as illustrated by the longer operating time, hospital stay and more quantity of patients got complication. Both groups indicated changes in inflammatory and immune aspects. Compared with the younger ones, elderly patients showed less quantity of preoperative basic immune cells, delayed immune responses after the surgical trauma of LC and hyporeactivity of inflammatory response when accepting LC. CONCLUSIONS: An examination of the inflammatory reaction and immune response after LC demonstrated that there are significant differences observed in two groups divided by age. Further studies with more samples are required to determine the exact relationship of perioperative immune change and higher adverse outcome rate of aged people.

Treg-specific demethylated region activity in isolated regulatory t lymphocytes is a surrogate for disease severity in hepatocellular carcinoma.

In certain unique conditions like viral infections of the liver like hepatitis B (HBV) and hepatitis C (HCV), activation of Tregs may be associated with chronicity of the viral infections and subsequent predisposition to development of hepatocellular carcinoma (HCC) by the integrated viral genome. In parallel, potential persistence of Tregs activity may lead to immune evasion of cancerous cells and thus persistence of the carcinomatous conditions. In this study, we hypothesized that although the relative proportions of Tregs may remain unaltered in HCC, persistence of activity of Tregs may lead to immune evasion in advanced stages of HCC. To examine the issue of activation of Treg in liver cancer pathogenesis, we obtained liver biopsy and peripheral blood samples from patients with advanced grades of HCC, isolated Tregs, and examined the methylation status of "Treg-specific demethylated region" (TSDR), a key region whose methylation suppresses Treg activity and demethylation stimulates its genomic activity. This study provides evidence of demethylation of TSDR, increased gene expression examined by luciferase assays, and nuclear translocation of key transcription factors that function as gene enhancers in CD4+CD25+FoxP3 regulatory T cells in advanced grades of HCC.

Association between TP53 Arg72Pro polymorphism and hepatocellular carcinoma risk: a meta-analysis.

BACKGROUND: Previous studies on the association between the TP53 Arg72Pro polymorphism and hepatocellular carcinoma (HCC) risk obtained controversial findings. This study aimed to quantify the strength of the association by meta-analysis. METHODS: We searched PubMed and Wangfang databases for published studies on the association between the TP53 Arg72Pro polymorphism and HCC risk, using the pooled odds ratio (OR) with its 95% confidence intervals (95% CI) for assessment. RESULTS: 10 studies with a total of 2,026 cases and 2,733 controls were finally included into this meta-analysis. Overall, the TP53 Arg72Pro polymorphism was not associated with HCC risk (all P values greaterth HCC risk in Caucasians in three genetic models (For Pro versus Arg, OR = 1.20, 95%CI 1.03-1.41; For ProPro versus ArgArg, OR = 1.74, 95%CI 1.23-2.47; For ProPro versus ArgPro/ArgArg, OR = 1.85, 95%CI 1.33-2.57). However, there was no significant association between the TP53 Arg72Pro polymorphism and HCC risk in East Asians (all P values greater than 0.10). No evidence of publication bias was observed. CONCLUSION: Meta-analyses of available data suggest an obvious association between the TP53 Arg72Pro and HCC risk in Caucasians. However, the TP53 Arg72Pro polymorphism may have a race-specific effect on HCC risk and further studies are needed to elucidate this possible effect.

Intraoperative radiofrequency ablation combined with 125 iodine seed implantation for unresectable pancreatic cancer.

AIM: To evaluate the feasibility, efficacy and safety of intraoperative radiofrequency ablation (RFA) combined with (125)iodine seed implantation for unresectable pancreatic cancer. METHODS: Thirty-two patients (21 males and 11 females) at the age of 68 years (range 48-90 years) with unresectable locally advanced pancreatic cancer admitted to our hospital from January 2006 to May 2008 were enrolled in this study. The tumor, 4-12 cm in diameter, located in pancreatic head of 23 patients and in pancreatic body and tail of 9 patients, was found to be unresectable during operation. Diagnosis of pancreatic cancer was made through intraoperative biopsy. Patients were treated with FRA combined with (125)iodine seed implantation. In brief, a RFA needle was placed, which was confirmed by intraoperative ultrasound to decrease the potential injury of surrounding vital structures, a (125)iodine seed was implanted near the blood vessels and around the tumor border followed by bypass palliative procedure (cholangio-jejunostomy and/or gastrojejunostomy) in 29 patients. RESULTS: The serum CA 19-9 level was decreased from 512 ± 86 U/mL before operation to 176 ± 64 U/mL, 108 ± 42 U/mL and 114 ± 48 U/mL, respectively, 1, 3 and 6 mo after operation (P < 0.05). The pain score on day 7 after operation, 1 and 3 mo after combined therapy was decreased from 5.86 ± 1.92 before operation to 2.65 ± 1.04, 1.65 ± 0.88 and 2.03 ± 1.16, respectively, after operation (P < 0.05). The rate of complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD) in 32 patients was 21.8% (7/32), 56.3% (18/32), 15.6% (5/32) and 6.3% (2/32), respectively, 6 mo after operation, with a median overall survival time of 17. 5 mo. The median survival time of patients at stage III was longer than that of those at stage IV (19 mo vs 10 mo, P = 0.0026). The median survival time of patients who received and did not receive chemotherapy after operation was 20 mo and 16 mo, respectively (P = 0.0176). Of the 32 patients, 3 (10.6%) experienced postoperative complications including transient biliary leaks in 2 patients and acute pancreatitis in 1 patient. All the patients recovered well after conservative support treatment. CONCLUSION: Intraoperative RFA combined with (125)iodine seed implantation is a feasible and safe procedure for unresectable pancreatic cancer with acceptable minor complications, and can prolong the survival time of patients, especially those at stage III.

Primary carcinoid tumor of the gallbladder: a case report and brief review of the literature.

BACKGROUND: Primary carcinoid tumor of the gallbladder is rare and comprises less than 1% of all carcinoid tumors. Preoperative diagnosis of carcinoid tumor of the gallbladder is difficult. The imageology findings are similar to those in other gallbladder cancers. CASE PRESENTATION: A 46-year-old woman was hospitalized with a preoperative diagnosis of gallbladder carcinoma, The patient was referred for surgical opinion and laparotomy was subsequently performed. A 4 x 5 cm mass was found within the gallbladder, located on the free surface of the body and fundus of the gallbladder. Neither metastases nor direct invasion to the liver was found. The entire mass and gallbladder were excised and intact. Histologically, the tumor consisted of small oval cells with round-to-oval neclei and tumor cells formed small nodular, trabeculare and acinar structures. The tumor showed moderate pleomorphism with scattered mitotic figures, but no definite evidence of vascular permeation, perineural invasion or lymphatic permeation was seen. The tumor cells invaded the mucosa extensively, and some penetrated the muscular layer but not through the serosa of the gallbladder into the liver. Immunohistochemical studies revealed strong positive reaction for chromogranin A and NSE. This lesion was proved to be a primary carcinoid tumor of the gallbladder. A brief review of literature, clinical feature, pathology and treatment of this rare disease was discussed. CONCLUSION: Primary carcinoid tumor of the gallbladder is uncommon. The definite diagnosis is often made on histopathological results after surgery.

Gallstone recurrence after successful percutaneous cholecystolithotomy: a 10-year follow-up of 439 cases.

BACKGROUND: Stone recurrence is a major problem in the medication of gallstones with gallbladder preservation. The aim of this study was to determine the long-term recurrence rate of gallstones and the clinical outcome after successful percutaneous cholecystolithotomy (PCCL) treatment, and to investigate the possible risk factors for gallstone recurrence. METHODS: After successful PCCL for gallstones, 439 patients were followed up during a 10-year period. The long-term gallstone recurrence rate and clinical outcome were evaluated. Risk factors associated with stone recurrence were identified. RESULTS: Gallstone recurrence was detected in 182 of 439 PCCL patients, giving an overall recurrence rate of 41.46%. The cumulative gallstone recurrence rate for each of the 10 post-operative years was 9.57%, 18.91%, 27.33%, 34.14%, 37.59%, 39.86%, 41.90%, 42.73%, 42.85%, and 43.21%, respectively. Among these recurrent patients, 94 were asymptomatic, 80 suffered from nonspecific upper gastrointestinal symptoms and 8 suffered from abdominal pain or biliary colic. Thirty-eight of the 182 patients were retreated with cholecystectomy. The risk factors for stone recurrence included a family history of gallstones, preference for fatty food, accompanying liver disease, multiple stones and poor gallbladder function pre-PCCL. CONCLUSIONS: In this study, the overall recurrence rate of gallstone was 41.46% during a 10-year period. The highest frequency of gallstone recurrence was during the 5th to 6th postoperative years and then continued to slowly increase. Risk factors for stone recurrence varied. We suggest that the use of PCCL in patients with gallstones should be considered carefully because of stone recurrence.