Percutaneous transhepatic intraportal biopsy using gastroscope biopsy forceps for diagnosis of a pancreatic neuroendocrine neoplasm: A case report.

BACKGROUND: Pancreatic neuroendocrine neoplasms (PNENs) are a rare group of neoplasms originating from the islets of the Langerhans. Portal vein tumor thrombosis has been reported in 33% of patients with PNENs. While the histopathological diagnosis of PNENs is usually based on percutaneous biopsy or endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA), these approaches may be impeded by gastric varices, poor access windows, or anatomically contiguous critical structures. Obtaining a pathological diagnosis using a gastroscope biopsy forceps via percutaneous transhepatic intravascular pathway is an innovative method that has rarely been reported. CASE SUMMARY: A 72-year-old man was referred to our hospital for abdominal pain and melena. Abdominal contrast-enhanced magnetic resonance imaging revealed a well-enhanced tumor (size: 2.4 cm × 1.2 cm × 1.2 cm) in the pancreatic tail with portal vein invasion. Traditional pathological diagnosis via EUS-FNA was not possible because of diffuse gastric varices. We performed a percutaneous transportal biopsy of the portal vein tumor thrombus using a gastroscope biopsy forceps. Histopathologic examination revealed a pancreatic neuroendocrine neoplasm (G2) with somatostatin receptors 2 (+), allowing systemic treatment. CONCLUSION: Intravascular biopsy using gastroscope biopsy forceps appears to be a safe and effective method for obtaining a histopathological diagnosis. Although well-designed clinic trials are required to obtain more definitive evidence, this procedure may help improve the diagnosis of portal vein thrombosis and related diseases.

Inhibition of the growth of human melanoma cells by methionine enkephalin.

Melanoma is an aggressive cancer, the incidence of which is increasing worldwide. Limited therapies are currently available, particularly following metastasis. The aim of the present study was to investigate the inhibiting effect of methionine enkephalin (MENK) on human melanoma via opioid receptors. The results of the present study revealed that MENK markedly regulates the proliferation of A375 cells, causing cell cycle arrest in G0/G1 phase and a decrease in the percentage of cells in S and G2/M phases. Reverse transcription­quantitative polymerase chain reaction demonstrated that MENK treatment increased opioid receptor expression in A375 cells. Furthermore, the expression level of survivin, an inhibitory apoptotic protein, was 1.1% of the level in the control group in the MENK group following 48 h of treatment. In conclusion, the results of the present study revealed, to the best of our knowledge for the first time, that MENK may inhibit growth and induce apoptosis of A375 cells, and describes a potential mechanism underlying these effects. Therefore, MENK should be investigated as a primary therapy for human melanoma cancer and as an adjuvant to other chemotherapies. Further studies are required to develop an optimal strategy for the use of MENK for the treatment of human cancers.

Human Enterovirus Nonstructural Protein 2CATPase Functions as Both an RNA Helicase and ATP-Independent RNA Chaperone.

RNA helicases and chaperones are the two major classes of RNA remodeling proteins, which function to remodel RNA structures and/or RNA-protein interactions, and are required for all aspects of RNA metabolism. Although some virus-encoded RNA helicases/chaperones have been predicted or identified, their RNA remodeling activities in vitro and functions in the viral life cycle remain largely elusive. Enteroviruses are a large group of positive-stranded RNA viruses in the Picornaviridae family, which includes numerous important human pathogens. Herein, we report that the nonstructural protein 2CATPase of enterovirus 71 (EV71), which is the major causative pathogen of hand-foot-and-mouth disease and has been regarded as the most important neurotropic enterovirus after poliovirus eradication, functions not only as an RNA helicase that 3'-to-5' unwinds RNA helices in an adenosine triphosphate (ATP)-dependent manner, but also as an RNA chaperone that destabilizes helices bidirectionally and facilitates strand annealing and complex RNA structure formation independently of ATP. We also determined that the helicase activity is based on the EV71 2CATPase middle domain, whereas the C-terminus is indispensable for its RNA chaperoning activity. By promoting RNA template recycling, 2CATPase facilitated EV71 RNA synthesis in vitro; when 2CATPase helicase activity was impaired, EV71 RNA replication and virion production were mostly abolished in cells, indicating that 2CATPase-mediated RNA remodeling plays a critical role in the enteroviral life cycle. Furthermore, the RNA helicase and chaperoning activities of 2CATPase are also conserved in coxsackie A virus 16 (CAV16), another important enterovirus. Altogether, our findings are the first to demonstrate the RNA helicase and chaperoning activities associated with enterovirus 2CATPase, and our study provides both in vitro and cellular evidence for their potential roles during viral RNA replication. These findings increase our understanding of enteroviruses and the two types of RNA remodeling activities.

Tumor necrosis factor-alpha gene -308G > A polymorphism alters the risk of hepatocellular carcinoma in a Han Chinese population.

BACKGROUND: The aim of the present study was to evaluate the influence of tumor necrosis factor-alpha (TNF-α) -308 G > A polymorphism on hepatocellular carcinoma (HCC) risk. METHODS: The present case-control study was conducted in a Han Chinese population consisting of 753 HCC patients and 760 controls from May 2010 to March 2013. The -308 TNF-a promoter polymorphisms were detected. Conditional logistic regression was performed to analyze the association between TNF-α -308 G > A polymorphism and the risk of HCC, which were estimated by odds ratios (ORs) and their 95% confidence intervals (95% CIs). RESULTS: The genotypic frequencies in the cases were not similar to that of the controls, differences being statistically significant (P = 0.002). Using the GG genotype as the reference genotype, AA was significantly associated with increased risk of HCC (adjusted OR = 5.12, 95% CI = 2.31-7.82). Similarly, AG + AA genotype showed 5.59-fold increased HCC risk in a dominant model. Furthermore, we found A allele was significantly associated with increased risk of HCC, compared with G allele (OR = 4.18, 95% CI = 1.76-6.97). CONCLUSION: The present study showed that TNF-α -308 G > A polymorphism was associated with increased HCC risk in a Han Chinese population. Further prospective studies on large and different ethnic populations will be necessary to confirm our findings and elucidate the underlying molecular mechanism for the development of HCC. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_199.

Expression of WASF3 in patients with non-small cell lung cancer: Correlation with clinicopathological features and prognosis.

Wiskott-Aldrich syndrome protein family member 3 (WASF3) is required for invasion and metastasis in different cancer cell types, and has been demonstrated to possess prognostic value in various types of human cancer. However, to the best of our knowledge, the expression profile of WASF3 and its correlations with the clinicopathological features of non-small cell lung cancer (NSCLC) have not yet been described. In the present study, the mRNA expression levels of WASF3, in 38 NSCLC patients and in matched normal tissues, were assessed using quantitative polymerase chain reaction and the protein expression in 96 specimens was analyzed using immunohistochemistry. In addition, patient survival data were collected retrospectively and the association between WASF3 expression and five-year overall survival was evaluated. The results demonstrated that the mRNA expression level of WASF3 in cancer tissues was markedly (approximately five times) higher compared with that of the normal tissues. The WASF3 protein expression profile in NSCLC was consistent with the mRNA expression result, which also correlated with the histological subtype and tumor stage. Furthermore, patients with WASF3-positive expression were associated with a poorer prognosis compared with those exhibiting WASF3-negative expression, and the five-year survival rate was 20.8 and 46.5%, respectively (Kaplan-Meier; log-rank, P=0.004). In the multivariate analysis, which included other clinicopathological features, WASF3 emerged as an independent prognostic factor (relative risk, 0.463; 95% CI, 0.271-0.792). These results indicate that WASF3 may be critical in the pathogenesis of NSCLC, in addition to being a valuable prognostic factor for NSCLC patients. Further investigations are required to identify the efficacy of WASF3 as a potential therapeutic target for the treatment of NSCLC.

Human IgG subclasses against enterovirus Type 71: neutralization versus antibody dependent enhancement of infection.

The emerging human enterovirus 71 (EV71) represents a growing threat to public health, and no vaccine or specific antiviral is currently available. Human intravenous immunoglobulin (IVIG) is clinical used in treating severe EV71 infections. However, the discovery of antibody dependent enhancement (ADE) of EV71 infection illustrates the complex roles of antibody in controlling EV71 infection. In this study, to identify the distinct role of each IgG subclass on neutralization and enhancement of EV71 infection, different lots of pharmaceutical IVIG preparations manufactured from Chinese donors were used for IgG subclass fractionation by pH gradient elution with the protein A-conjugated affinity column. The neutralization and ADE capacities on EV71 infection of each purified IgG subclass were then assayed, respectively. The neutralizing activity of human IVIG is mainly mediated by IgG1 subclass and to less extent by IgG2 subclass. Interestingly, IgG3 fraction did not have neutralizing activity but enhanced EV71 infection in vitro. These results revealed the different roles of human IgG subclasses on EV71 infection, which is of critical importance for the rational design of immunotherapy and vaccines against severe EV71 diseases.

MDCT angiography to evaluate the therapeutic effect of PTVE for esophageal varices.

AIM: To evaluate the role of multi-detector row computed tomography (MDCT) angiography for assessing the therapeutic effects of percutaneous transhepatic variceal embolization (PTVE) for esophageal varices (EVs). METHODS: The subjects of this prospective study were 156 patients who underwent PTVE with cyanoacrylate for EVs. Patients were divided into three groups according to the filling range of cyanoacrylate in EVs and their feeding vessels: (1) group A, complete obliteration, with at least 3 cm of the lower EVs and peri-/EVs, as well as the adventitial plexus of the gastric cardia and fundus filled with cyanoacrylate; (2) group B, partial obliteration of varices surrounding the gastric cardia and fundus, with their feeding vessels being obliterated with cyanoacrylate, but without reaching lower EVs; and (3) group C, trunk obliteration, with the main branch of the left gastric vein being filled with cyanoacrylate, but without reaching varices surrounding the gastric cardia or fundus. We performed chart reviews and a prospective follow-up using MDCT images, angiography, and gastrointestinal endoscopy. RESULTS: The median follow-up period was 34 mo. The rate of eradication of varices for all patients was 56.4% (88/156) and the rate of relapse was 31.3% (41/131). The rates of variceal eradication at 1, 3, and 5 years after PTVE were 90.2%, 84.1% and 81.7%, respectively, for the complete group; 61.2%, 49% and 42.9%, respectively, for the partial group; with no varices disappearing in the trunk group. The relapse-free rates at 1, 3 and 5 years after PTVE were 91.5%, 86.6% and 81.7%, respectively, for the complete group; 71.1%, 55.6% and 51.1%, respectively, for the partial group; and all EVs recurred in the trunk group. Kaplan-Meier analysis showed P values of 0.000 and 0.000, and odds ratios of 3.824 and 3.603 for the rates of variceal eradication and relapse free rates, respectively. Cyanoacrylate in EVs disappeared with time, but those in the EVs and other feeding vessels remained permanently in the vessels without a decrease with time, which is important for the continued obliteration of the feeding vessels and prevention of EV relapse. CONCLUSION: MDCT provides excellent visualization of cyanoacrylate obliteration in EV and their feeding veins after PTVE. It confirms that PTVE is effective for treating EVs.

Percutaneous transhepatic variceal embolization combined with endoscopic ligation for the prevention of variceal rebleeding.

OBJECTIVE: To compare the efficiency of percutaneous transhepatic variceal embolization (PTVE) plus endoscopic variceal ligation (EVL) with EVL alone in the treatment of esophageal variceal bleeding. METHODS: Cirrhotic patients with recent esophageal variceal bleeding from January 2007 to December 2011 were collected and assigned to PTVE + EVL (N = 41) or EVL (N = 47) groups. We performed chart reviews and prospective follow-up to determine variceal rebleeding, recurrence of varices and survival. RESULTS: During the follow-up period, recurrence of esophageal varices (EV) occurred in 8 patients (19.5%) in the PTVE + EVL group and 23 (48.9%) in the EVL group (P = 0.004). The time to recurrence of EV was 9.2 ± 2.7 months and 4.9 ± 2.1 months, respectively. Three patients (7.3%) in the PTVE + EVL group and 12 (25.5%) in the EVL group experienced rebleeding from all sources (P = 0.023). One patient (2.4%) in the PTVE + EVL group and 7 (14.9%) in the EVL group experienced rebleeding from EV (P = 0.024). Multivariate Cox analysis indicated that the treatment method was the only predictor of rebleeding. There was no significant difference in the survival rate between the two groups. CONCLUSION: With adequate and permanent obliteration of EV and their feeding veins, the combination of PTVE with cyanoacrylate and EVL is more effective than EVL alone in the prevention and treatment of EV recurrence and rebleeding.

Combined Intestinal and Biliary Stenting in Gastric Outlet and Biliary Obstruction.

BACKGROUND: Combined intestinal and biliary stenting is one of the effective palliative methods for patients with malignant gastric outlet and biliary obstruction. This study was to evaluate the effect of combined intestinal and biliary stenting in the palliation of gastric outlet and biliary obstruction. METHODS: Thirty-two patients with malignant gastric outlet and biliary obstruction underwent combined intestinal and biliary stenting. Intestinal stents were implanted by means of endoscopy and X-ray guidance. The subsequent biliary stents were implanted by percutaneous transhepatic cholangial drainage. The biliary stent pass through the side hole of intestinal stent mesh and its distal segment was located in the lumen of intestinal stent. RESULTS: Thirty-four intestinal stents and 32 biliary stents for 32 patients were implanted successfully. No lethal complications occurred. The average survival was 164 days. CONCLUSIONS: The combined intestinal and biliary stenting is an effective and safe method for palliation of gastric outlet and biliary obstructions. The short-term results are satisfactory.

Percutaneous Biliary Stent Placement in Palliation of Malignant Bile Duct Obstruction.

BACKGROUND: To summarize the experiences with the technique of percutaneous biliary stent placement for treatment of malignant biliary obstruction in patients with different types of biliary obstruction. METHODS: Percutaneous biliary stent placement was performed in 126 patients with malignant biliary obstruction. The etiology included 56 cases of cholangiocarcinoma, 28 cases of pancreatic cancer, 12 cases of ampullary carcinoma, 10 cases of primary hepatic carcinoma, 8 cases of gastric cancer metastasis, 6 cases of gallbladder carcinoma, and 6 cases of liver metastasis of colon cancer. The obstructed lesion predominantly involved the common bile duct in 42 patients, common hepatic duct in 39 patients, and hilar bile duct in 45 patients. When the bile duct was punctured successfully under fluoroscopy, the guide wire was explored to across the obstruction segment under the assistant of catheter, then the stent was inserted along the super-slippery guide wire. In patients with hilar hepatic duct lesions involving both left and right hepatic ducts, the both ducts were punctured and bilateral stenting was performed. A 8.5 F internal/external drainage catheter was inserted. The liver function test and ultrasound were performed one week after the procedure to observe the decrease of bilirubin and alleviation of biliary obstruction. RESULTS: A total of 166 stents were implanted in 126 patients. In the 42 patients with common bile duct obstruction, each patient was implanted one stent. In the 39 patients with common hepatic duct obstruction, each patient was impanted one stent. In the 45 patients with hilur bile duct obstruction, 38 patients were placed 2 stents, one patient was placed with 3 stents, and the rest were placed with one stent. The serum total bilirubin decreased from 309.2 ± 158.3 µmol/L before the procedure to148.5 ± 98.0 µmol/L one week after the procedure (P < 0.001). Alkaline phosphatase and alanine aminotransferase significantly decreased (P < 0.001). Five cases died within 1 month (4%) after the procedure. Complications occurred in 9 cases (7.1%). Six patients underwent combined duodenal self-expandable metal stent placement successfully. CONCLUSIONS: The percutaneous biliary stent placement is a safe and effective palliative therapy for malignant biliary obstruction by improving liver function and 1ife quality.