Hepatitis B or C viral infection and risk of pancreatic cancer: A meta-analysis of observational studies

AIM: To investigate if there is an association between hepatitis B virus (HBV) or hepatitis C virus (HCV) infection and the risk of pancreatic cancer. METHODS: All relevant studies published before 11 October, 2012 were identified by a systematic search of MEDLINE, EMBASE, BIOSIS Previews and the Cochrane Library databases and with cross-referencing. The observational studies that reported RR or OR estimates with 95%CIs for the association between HBV or HCV and pancreatic cancer were included. A random-effects model was used to summarize meta-analytic estimates. The Newcastle-Ottawa quality assessment scale was applied to assess the quality of the methodology in the included studies. RESULTS: A total of 8 eligible studies were selected for meta-analysis. Overall, chronic hepatitis B and inactive hepatitis B surface antigen (HBsAg) carrier state (HBsAg positive) had a significantly increased risk of pancreatic cancer with OR of 1.20 (95%CI: 1.01-1.39), especially in the Chinese population (OR = 1.30, 95%CI: 1.05-1.56). Past exposure to HBV (possible occult HBV infection) had an increased OR of pancreatic cancer risk (OR = 1.24, 95%CI: 1.05-1.42), especially among those patients without natural immunity [anti hepatitis B core (HBc) positive/hepatitis B surface antibody (anti HBs) negative], with OR of 1.67 (95%CI: 1.13-2.22). However, past exposure to HBV with natural immunity (anti-HBc positive/anti-HBs positive) had no association with pancreatic cancer development, with OR 0.98 (95%CI: 0.80-1.16), nor did the HBV active replication (hepatitis B e antigen positive status), with OR 0.98 (95%CI: 0.27-1.68). The risk of pancreatic cancer among anti-HBs positive patients was significantly lower than among anti-HBs negative patients (OR = 0.54, 95%CI: 0.46-0.62). Past exposure to HCV also resulted in an increased risk of pancreatic cancer (OR = 1.26, 95%CI: 1.03-1.50). Significant between-study heterogeneity was observed. Evidence of publication bias for HBV/HCV infection-pancreatic cancer association was not found. CONCLUSION: Chronic HBV and HCV infection increases pancreatic cancer risk. Our findings underscore the need for more studies to confirm this potential relationship.

Correlation of fibrinogen-like protein 2 with progression of acute pancreatitis in rats

AIM: To examine fibrinogen-like protein 2 (fgl2) expression during taurocholate-induced acute pancreatitis progression in rats and its correlation with pancreatic injury severity. METHODS: Forty-eight male Sprague-Dawley rats were randomly divided into the severe acute pancreatitis (SAP) group (n = 24) and the sham operation (SO) group (n = 24). Sodium taurocholate (4% at doses of 1 mL/kg body weight) was retrogradely injected into the biliopancreatic ducts of the rats to induce SAP. Pancreatic tissues were prepared immediately after sacrifice. At the time of sacrifice, blood was obtained for determination of serum amylase activity and isolation of peripheral blood mononuclear cells (PBMCs). Pancreatic tissue specimens were obtained for routine light microscopy including hematoxylin and eosin staining, and the severity of pancreatic injury was evaluated 1, 4 and 8 h after induction. Expression of fgl2 mRNA was measured in the pancreas and PBMCs using reverse transcription polymerase chain reaction. Expression of fgl2 protein was evaluated in pancreatic tissues using Western blotting and immunohistochemical staining. Masson staining was also performed to observe microthrombosis. RESULTS: At each time point, levels of fgl2 mRNAs in pancreatic tissues and PBMCs were higher (P < 0.05) in the SAP group than in the SO group. For pancreatic tissue in SAP vs SO, the levels were: after 1 h, 3.911 ± 1.277 vs 1.000 ± 0.673; after 4 h, 9.850 ± 3.095 vs 1.136 ± 0.609; and after 8 h, 12.870 ± 3.046 vs 1.177 ± 0.458. For PBMCs in SAP vs SO, the levels were: after 1 h, 2.678 ± 1.509 vs 1.000 ± 0.965; after 4 h, 6.922 ± 1.984 vs 1.051 ± 0.781; and after 8 h, 13.533 ± 6.575 vs 1.306 ± 1.179. Levels of fgl2 protein expression as determined by Western blotting and immunohistochemical staining were markedly up-regulated (P < 0.001) in the SAP group compared with those in the SO group. For Western blotting in SAP vs SO, the results were: after 1 h, 2.183 ± 0.115 vs 1.110 ± 0.158; after 4 h, 2.697 ± 0.090 vs 0.947 ± 0.361; and after 8 h, 3.258 ± 0.094 vs 1.208 ± 0.082. For immunohistochemical staining in SAP vs SO, the results were: after 1 h, 1.793 ± 0.463 vs 0.808 ± 0.252; after 4 h, 4.535 ± 0.550 vs 0.871 ± 0.318; and after 8 h, 6.071 ± 0.941 vs 1.020 ± 0.406. Moreover, we observed a positive correlation in the pancreas (r = 0.852, P < 0.001) and PBMCs (r = 0.735, P < 0.001) between fgl2 expression and the severity of pancreatic injury. Masson staining showed that microthrombosis (%) in rats with SAP was increased (P < 0.001) compared with that in the SO group and it was closely correlated with fgl2 expression in the pancreas (r = 0.842, P < 0.001). For Masson staining in SAP vs SO, the results were: after 1 h, 26.880 ± 9.031 vs 8.630 ± 3.739; after 4 h, 53.750 ± 19.039 vs 8.500 ± 4.472; and after 8 h, 80.250 ± 12.915 vs 10.630 ± 7.003.CONCLUSION: Microthrombosis due to fgl2 overexpression contributes to pancreatic impairment in rats with SAP, and fgl2 level may serve as a biomarker during early stages of disease.

EVALUATION OF CIRRHOTIC LIVER WITH PERFUSION-WEIGHTED MAGNETIC RESONANCE IMAGING:A PRELIMINARY EXPERIMENTAL STUDY IN ANIMAL MODELS WITH HALF-LIVER CIRRHOSIS

Objective To investigate the role of perfusion-weighted magnetic resonance imaging (MRI) in evaluation of cirrhotic liver. Methods With a 4F catheter, 1% diluted carbon tetrachloride (1 ml/kg) was selectively injected into right or left hepatic artery of 12 dogs fortnightly. The half liver into which carbon tetrachloride was injected was called as study side (SS), while the other half liver without carbon tetrachloride injection was called as study control side (SCS). Conventional and perfusion-weighted MRI were performed in every 4 weeks. Via a 4F catheter, 5ml gadolinium diethylentriamine pentaaceti acid (Gd-DTPA) dilution was injected into superior mesenteric artery at the 5th scan. The signal intensity-time curves of SS, SCS, and portal vein were completed in MR workstation. The maximal relative signal increase (MRSI), peak time (t_ p ), and slope of the curves were measured. Results On conventional MR images, no abnormalities of externality and signal intensity were observed in both SS and SCS of liver at each stage. The mean t_ p , MRSI, and slope of intensity-time curves in normal liver were 10.56 seconds, 1.01, and 10.23 arbitrary unit (au)/s, respectively. Three parameters of curves didn’t show obvious change in SCS of liver at every stage. Abnormal perfusion curves occurred in SS of liver at the 12th week after the 1st injection. The abnormality of perfusion curve in SS was more and more serious as the times of injection increased. The mean t_ p , MRSI, and slope intensity-time curves in SS of liver were 19.45 seconds, 0.43, and 3.60 au/s respectively at the 24th week. Conclusion Perfusion-weighted imaging can potentially provide information about portal perfusion of hepatic parenchyma, and to some degree, reflect the severity of cirrhosis.

Smoking, alcohol consumption, and the risk of extrahepatic cholangiocarcinoma:A meta-analysis

AIM:To assess the association between smoking and alcohol consumption and extrahepatic cholangiocarcinoma(ECC)through a meta-analysis of clinical observational studies.METHODS:A literature search was conducted using Embase and MEDLINE databases from inception to 31May 2013 without language limitations,and by manually searching the references of retrieved articles.Casecontrol and cohort studies that investigated the association between smoking or alcohol consumption and ECC were included.The quality of these studies was assessed using the Newcastle-Ottawa quality assessment scale.Summary relative risks and corresponding95%CI were calculated using a random-effects model.Publication bias was assessed by Begg’s funnel plot and Egger’s test.RESULTS:A total of 12 eligible articles(11 case-control studies and one cohort study)were included in this meta-analysis.Eleven studies reported the association between smoking and ECC.Pooled analysis indicated that smokers had an increased risk of ECC development as compared with non-smokers(summary RR=1.23;95%CI:1.01-1.50).This correlation was present in population-based studies(n=5;summary RR=1.47;95%CI:1.06-2.05)but not in hospital-based studies(n=6;summary RR=1.10;95%CI:0.88-1.37)and in non-Asian regions(n=7;summary RR=1.39;95%CI:1.03-1.87)but not in Asia(n=4;summary RR=1.08;95%CI:0.85-1.38).Seven studies reported an association between consuming alcohol and ECC.Pooled analysis indicated that alcohol drinkers had a similar risk of ECC development as did individuals who did not drink alcohol(summary RR=1.09;95%CI:0.87-1.37).There was moderate heterogeneity among the studies and no evidence of publication bias.CONCLUSION:Smoking is associated with an increased risk of ECC,but alcohol consumption is not.Further population-based studies,particularly cohort studies,are warranted to enable definitive conclusions.

Appendiceal bleeding:A case report

BACKGROUND Acute lower gastrointestinal bleeding is common in clinical practice,and the colon is responsible for the majority of cases.However,appendiceal bleeding is an extremely rare cause.Appendiceal bleeding due to vascular diseases,such as angiodysplasia and Dieulafoy’s lesion,may result in massive lower gastrointestinal bleeding.Appendectomy is a reliable and effective option for treatment.CASE SUMMARY A 32-year-old male presented to our hospital with hematochezia that had lasted for 6 h,with approximately 600-800 m L bloody stools and loss of consciousness for a few seconds.Persistent bleeding from the orifice of the appendix was observed by colonoscopy.Following the new diagnosis of appendiceal bleeding,the patient was treated by an emergency laparoscopic appendectomy.Finally,the patient was pathologically diagnosed with appendiceal Dieulafoy’s lesion.The patient was uneventfully discharged,and follow-up 2 wk later showed no evidence of rebleeding.CONCLUSION Although appendiceal bleeding is a rare cause of acute lower gastrointestinal bleeding,clinicians should consider it during differential diagnosis.

Depletion of telomerase RNA inhibits growth of gastrointestinal tumors transplanted in mice

AIM: To explore effects of telomerase RNA-targeting phosphorothioate antisense oligodeoxynucleotides (PS-ASODN) on growth of human gastrointestinal stromal tumors transplanted in mice. METHODS: A SCID mouse model for transplantation of human gastrointestinal stromal tumors (GISTs) was established using tumor cells from a patient who was diagnosed with GIST and consequently had been treated with imatinib. GIST cells cultured for 10 passages were used for inoculation into mice. Transfection of PS-ASODN was carried out with Lipotap Liposomal Transfection Reagent. GISTs that subsequently developed in SCID mice were subjected to intratumoral injection once daily from day 7 to day 28 postinoculation, and mice were divided into the following four groups according to treatment: PS-ASODN group (5.00 μmoL/L of oligonucleotide, each mouse received 0.2 mL once daily); imatinib group (0.1 mg/g body weight); liposome negative control group (0.01 mL/g); and saline group (0.01 mL/g). On day 28, the mice were sacrificed, and tumor attributes including weight and longest and shortest diameters were measured. Tumor growth was compared between treatment groups, and telomerase activity was measured by enzyme-linked immunosorbent assay. Apoptosis was examined by flow cytometry. Real-time polymerase chain reaction was used to detect expression of the mRNA encoding the apoptosis inhibition B-cell leukemia/lymphoma 2 (bcl-2 ) gene. RESULTS: In the PS-ASODN group, tumor growth was inhibited by 59.437%, which was markedly higher than in the imatinib group (11.071%) and liposome negative control group (2.759%) [tumor inhibition=(mean tumor weight of control group - mean tumor weight of treatment group)/(mean tumor weight of control group) × 100%]. Telomerase activity was significantly lower (P < 0.01) in the PS-ASODN group (0.689 ± 0.158) compared with the imatinib group (1.838 ± 0.241), liposome negative control group (2.013 ± 0.273), and saline group (2.004 ± 0.163). Flow cytometry revealed that the apoptosis rate of tumor cells treated with PS-ASODN was 20.751% ± 0.789%, which was higher (P < 0.01) than that of the imatinib group (1.163% ± 0.469%), liposome negative control group (1.212% ± 0.310%), and saline group (1.172% ± 0.403%). Expression of bcl-2 mRNA in the transplanted GISTs was markedly downregulated (P < 0.01) in the PS-ASODN group (7.245 ± 0.739) compared with the imatinib group (14.153 ± 1.618) and liposome negative control group (16.396 ± 1.351).CONCLUSION: PS-ASODN can repress GIST growth, mediated perhaps by inhibition of telomerase activity and downregulation of bcl-2 expression.

Segmental small bowel necrosis associated with antiphospholipid syndrome:A case report

Antiphospholipid syndrome is a multi-system disease characterized by the formation of thromboembolic complications and/or pregnancy morbidity, and with persistently increased titers of antiphospholipid antibodies. We report the case of a 50-year-old, previously healthy man who presented with fever and new-onset, dull abdominal pain. A contrast-enhanced computed tomography scan showed segmental small bowel obstruction, for which an emergency laparotomy was performed. Histopathologic examination of resected tissues revealed multiple intestinal and mesenteric thromboses of small vessels. Laboratory tests for serum antiphospholipid(anticardiolipin Ig M) and anti-β2-glycoprotein I antibodies were positive. Despite proactive implementation of anticoagulation, steroid, and antibiotic therapies, the patient's condition rapidly deteriorated, and he died 22 d after admission. This case highlights that antiphospholipid syndrome should be suspected in patients with unexplainable ischemic bowel and intestinal necrosis presenting with insidious clinical features that may be secondary to the disease, as early diagnosis is critical to implement timely treatments in order to ameliorate the disease course.