AIM: To evaluate potential risk factors in the development of ulcerative colitis (UC) in China.
METHODS: A total of 1308 patients with UC and 1308 age-matched and sex-matched controls were prospectively studied in China. The UC cases were collected from 17 hospitals in China from April 2007 to April 2010. Uniform questionnaires were designed to investigate risk factors including smoking, appendectomy, stress, socio-economic conditions, nonsteroidal anti-inflammatory drugs (NSAIDs), oral contraceptives, diet, breastfeeding, infections and family sanitary conditions. Group comparisons by each factor were done using simple logistic regression analysis. Conditional logistic regression was used for multivariate analysis.
RESULTS: By univariate analysis, the variables predictive of UC included feeling stress, light and heavy alcoholic drinking, spicy food, sugar consumption and infectious diarrhea, while heavy tea intake and tap water consumption were protective against UC. On multivariate analysis, the protective factor for UC was tap water consumption [odds ratios (OR) = 0.424, 95%CI: 0.302-0.594, P < 0.001]; while the potential risk factors for UC were heavy sugar consumption (OR = 1.632, 95%CI: 1.156-2.305, P < 0.001), spicy food (light intake: OR = 3.329, 95%CI: 2.282-4.857, P < 0.001; heavy intake: OR = 3.979, 95%CI: 2.700-5.863, P < 0.001), and often feeling stress (OR = 1.981, 95%CI: 1.447-2.711, P < 0.001). Other factors, such as smoking habit, appendectomy, breastfeeding, a history of measles, rural or urban residence, education, oral contraceptives, and NSAID use have not been found to have a significant association with the development of UC in the present study.
CONCLUSION: Our study showed tap water consumption was a protective factor for UC, while spicy food, heavy sugar consumption and often feeling stress were risk factors for UC in this Chinese population.
Ulcerative colitis; Risk factors; Case-control study
AIM: To investigate the effect of probiotics on regulating T regulatory cells and reducing the severity of experimental colitis in mice.
METHODS: Forty C57/BL mice were randomly divided into four groups. Colitis was induced in the mice using 2,4,6-trinitrobenzene sulfonic acid (TNBS). After 10-d treatment with Bifico capsules (combined bifidobacterium, lactobacillus and enterococcus), body weight, colonic weight, colonic weight index, length of colon, and histological scores were evaluated. CD4+CD25+Foxp3+T cell in mesenteric lymph nodes were measured by flow cytometry, and cytokines in colonic tissue homogenates were analyzed by a cytometric bead array.
RESULTS: The colonic weight index and the colonic weight of colitis mice treated with Bifico were lower than that of TNBS-induced mice without treatment. However, colonic length and percent of body weight amplification were higher than in TNBS-induced mice without treatment. Compared with TNBS-induced mice without treatment, the level of CD4+CD25+Foxp3+T cells in mesenteric lymph nodes, the expression of interleukin (IL)-2, IL-4 and IL-10 in colonic tissues from colitis mice treated with Bifico were upregulated, and tumor necrosis factor-α and interferon-γ were downregulated.
CONCLUSION: Probiotics effectively treat experimental colitis by increasing CD4+CD25+Foxp3+T cell and regulating the balance of Th1 and Th2 cytokines in the colonic mucosa.
Probiotics; Ulcerative colitis; CD4+CD25+T cell; Cytokine
AIM: To study the effects of combined early fluid resuscitation and hydrogen inhalation on septic shock-induced lung and intestine injuries.
METHODS: Wistar male rats were randomly divided into four groups: control group (Group A, n = 15); septic shock group (Group B, n = 15); early fluid resuscitation-treated septic shock group (Group C, n = 15); and early fluid resuscitation and inhalation of 2% hydrogen-treated septic shock group (Group D, n = 15). The activity of hydroxyl radicals, myeloperoxidase (MPO), superoxide dismutase (SOD), diamine oxidase (DAO), and the concentration of malonaldehyde (MDA) in the lung and intestinal tissue were assessed according to the corresponding kits. Hematoxylin and eosin staining was carried out to detect the pathology of the lung and intestine. The expression levels of interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-α in lung and intestine tissue were detected by enzyme-linked immunosorbent assay method. The expression levels of Fas and Bcl2 in lung tissues were determined by immunohistochemistry and Western blotting.
RESULTS: Septic shock elicited a significant increase in the levels of MDA (10.17 ± 1.12 nmol/mg protein vs 2.98 ± 0.64 nmol/mg protein) and MPO (6.79 ± 1.02 U/g wet tissue vs 1.69 ± 0.14 U/g wet tissue) in lung tissues. These effects were not significantly decreased by Group C pretreatment, but were significantly reduced by Group D pretreatment (MDA: 4.45 ± 1.13 nmol/mg protein vs 9.56 ± 1.37 nmol/mg protein; MPO: 2.58 ± 0.21 U/g wet tissue vs 6.02 ± 1.16 U/g wet tissue). The activity of SOD (250.32 ± 8.56 U/mg protein vs 365.78 ± 10.26 U/mg protein) in lung tissues was decreased after septic shock, and was not significantly increased by Group C pretreatment, but was significantly enhanced by Group D pretreatment (331.15 ± 9.64 U/mg protein vs 262.98 ± 5.47 U/mg protein). Histological evidence of lung hemorrhage, neutrophil infiltration and overexpression of IL-6, IL-8, and TNF-α was observed in lung tissues, all of which were attenuated by Group C and further alleviated by Group D pretreatment. Septic shock also elicited a significant increase in the levels of MDA, MPO and DAO (6.54 ± 0.68 kU/L vs 4.32 ± 0.33 kU/L) in intestinal tissues, all of which were further increased by Group C, but significantly reduced by Group D pretreatment. Increased Chiu scoring and overexpression of IL-6, IL-8 and TNF-α were observed in intestinal tissues, all of which were attenuated by Group C and further attenuated by Group D pretreatment.
CONCLUSION: Combined early fluid resuscitation and hydrogen inhalation may protect the lung and intestine of the septic shock rats from the damage induced by oxidative stress and the inflammatory reaction.
Early fluid resuscitation; Inhalation of hydrogen gas; Septic shock; Lung; Intestine; Oxidative damage
AIM: To explore the prognostic value in the monitoring of treatment efficacy of serial α-fetoprotein (AFP) in hepatocellular carcinoma (HCC) patients.
METHODS: We searched MEDLINE, EMBASE and COCHRANE LIBRARY through April 21, 2012, to find qualifying articles. Our overall search strategy included terms for HCC, AFP, treatment response, and prognosis. Literature was limited to English-language, human studies. Studies reporting cumulative survival rates were summarized qualitatively. For the prognostic meta-analysis, we undertook a series of meta-analyses that summarised the Cox proportional hazard ratios (HRs) by assuming a random effects model. With regards to the correlation of AFP change with radiologic response, the categorical dichotomous variables were assessed using Poisson relative risks (RRs), which were incorporated into the random effects model meta-analysis of accuracy prediction. Between-study heterogeneity was estimated by use of the I² statistic. Publication bias was evaluated using the Begg funnel plot and Egger plot. Sensitivity analyses were conducted first by separating systemic treatment estimates from locoregional therapy estimates, evaluating different AFP response cut-off point effects, and exploring the impact of different study sizes.
RESULTS: Of 142 titles identified in our original search, 11 articles (12 clinical studies) met our criteria. Six studies investigated outcome in a total of 464 cases who underwent systemic treatment, and six studies investigated outcome in a total of 510 patients who received locoregional therapy. A random-effects model meta-analysis showed that AFP response was associated with an mortality HR of 0.55 (95%CI, 0.47-0.65) across HCC in overall survival (OS) and 0.50 (95%CI, 0.38-0.65) in progression-free survival. Restricting analysis to the six eligible analyses of systemic treatment, the pooled HRs were 0.64 (95%CI, 0.53-0.77) for OS. Limiting analysis to the six analyses of locoregional therapy, the pooled HRs for OS was 0.39 (95%CI, 0.29-0.53). We showed a larger pooled HR in the 50% definition studies (HR, 0.67, 95%CI, 0.55-0.83) compared with that from the 20% definition studies (HR, 0.41, 95%CI, 0.32-0.53). Restricting analysis to the four studies including over 100 patients individually, the pooled HR was 0.65 (95%CI, 0.54-0.79), with a pooled HR for OS of 0.35 (95%CI, 0.23-0.46) in the studies of less than 100 patients. As to radiological imaging, 43.1% (155/360) of the patients in the AFP response group presented with a radiological overall response, while the response rate decreased to 11.5% (36/313) in the patients from the AFP nonresponse group. The RR of having no overall response was significantly lower in the AFP response group than the AFP nonresponse group (RR, 0.67; 95%CI, 0.61-0.75). In terms of disease control rate, 86.9% (287/330) in the AFP response group and 51.0% (153/300) in the AFP nonresponse group showed successful disease control, respectively. The RR of disease control failure, similarly, was significantly lower in the AFP response group (RR, 0.37; 95%CI, 0.23-0.58). But these ﬁndings could be overestimates because of publication and reporting bias.
CONCLUSION: HCC patients presenting with an AFP response are at decreased risk of mortality. In addition, patients with an AFP response also present with a higher overall response rate and disease control rate.
Liver cancer; α-fetoprotein; Response; Prognosis; Monitoring
AIM: To investigate the prevalence of gallstone disease (GSD) and to evaluate the risk of symptomatic GSD among diabetic patients.
METHODS: The study was conducted by analyzing the National Health Research Institutes (NHRI) dataset of ambulatory care patients, inpatient claims, and the updated registry of beneficiaries from 2000 to 2008. A total of 615 532 diabetic patients without a prior history of hospital treatment or ambulatory care visits for symptomatic GSD were identified in the year 2000. Age- and gender-matched control individuals free from both GSD and diabetes from 1997 to 1999 were randomly selected from the NHIR database (n = 614 871). The incidence densities of symptomatic GSD were estimated according to the subjects’ diabetic status. The distributions of age, gender, occupation, income, and residential area urbanization were compared between diabetic patients and control subjects using Cox proportion hazards models. Differences between the rates of selected comorbidities were also assessed in the two groups.
RESULTS: Overall, 60 734 diabetic patients and 48 116 control patients developed symptomatic GSD and underwent operations, resulting in cumulative operation rates of 9.87% and 7.83%, respectively. The age and gender distributions of both groups were similar, with a mean age of 60 years and a predominance of females. The diabetic group had a significantly higher prevalence of all comorbidities of interest. A higher incidence of symptomatic GSD was observed in females than in males in both groups. In the control group, females under the age of 64 had a significantly higher incidence of GSD than the corresponding males, but this difference was reduced with increasing age. The cumulative incidences of operations for symptomatic GSD in the diabetic and control groups were 13.06 and 9.52 cases per 1000 person-years, respectively. Diabetic men exhibited a higher incidence of operations for symptomatic GSD than did their counterparts in the control group (12.35 vs 8.75 cases per 1000 person-years).
CONCLUSION: The association of diabetes with increased symptomatic GSD may provide insight to the treatment or management of diabetes in clinical settings.
Gallstone disease; Diabetes; Symptomatic; Incidence density; Hazard ratio
AIM: To analyze the possible protective role of Arctium lappa L. (AL) in a murine model of ulcerative colitis (UC).
METHODS: BALB/c mice were administered 100 mg/kg AL powder orally each day. After 7 d, colitis was induced by administration of dextran sulfate sodium (DSS) (5% W/V) in drinking water for a further 8 consecutive days. Diarrhea and bloody stools as well as colonic histology were observed. The level of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in colonic sections were detected by immunohistochemistry.
RESULTS: There were significant differences in mean body weight values and disease activity indices between controls and AL-treated animals. Moreover, the histological findings showed that AL treatment can prevent mucosal edema, submucosal erosions, ulceration, inflammatory cell infiltration and colon damage. In addition, immunohistochemistry analysis showed that the levels of the inflammatory cytokines, IL-6 and TNF-α were also decreased in AL-treated groups.
CONCLUSION: We suggest that AL can prevent intestinal damage and decrease inflammatory cytokines in mice with DSS-induced colitis. Thus, AL could prove to be a useful food for UC.
Arctium lappa L.; Colitis; Cytokine; Inflammatory bowel disease; Ulcerative colitis
AIM: To evaluate the value of the hepatitis B virus (HBV) replication mouse model with regard to several aspects of the study of HBV biology.
METHODS: To evaluate the HBV replication mouse model in detecting the efficacy of anti-HBV agents, the interferon inducer polyinosinic-polytidylin acid (polyIC) and nucleotide analogues adefovir and entecavir were administered to mice injected with wild type pHBV4.1, and the inhibiting effect of these agents on HBV DNA replication was evaluated. To identify the model’s value in a replication ability study of HBV drug-resistant mutants and a HBx-minus mutant, telbivudine resistance mutants (rtM204I, ayw subtype), adefovir resistance mutants (rtA181V + rtN236T, ayw subtype) and HBx-minus mutants were injected respectively, and their corresponding HBV DNA replication intermediates in mouse liver were assessed.
RESULTS: Compared with the wild type HBV replication mouse model without antiviral agent treatment, the HBV DNA replication intermediates of the polyIC-treated group were decreased 1-fold; while in the entecavir- and adefovir-treated groups, the levels of HBV DNA replication intermediates were inhibited 13.6-fold and 1.4-fold, respectively. For the mouse models injected with telbivudine resistance mutant, adefovir resistance mutant and HBx-minus mutant, HBV DNA replication intermediates could still be detected, but the levels of HBV DNA replication intermediates of these mutants decreased 4.5-fold, 5.6-fold and 2.9-fold respectively, compared with the mouse model with wild type HBV plasmid.
CONCLUSION: The HBV replication mouse model we established was a useful and convenient tool to detect the efficacy of antiviral agents and to study the replication ability of HBV mutants in vivo.
Hepatitis B virus; Antiviral agents; Drug resistance; Mutants; Mouse model
AIM: To investigate and evaluate the pathological features and diagnostic value of focal nodular hyperplasia (FNH) with multi-section spiral computed tomography (MSCT) and postprocessing.
METHODS: A total of 25 patients with FNH who had undergone MSCT and postprocessing were included in the investigation. All patients had been pathologically or clinically confirmed with FNH. A number of 75 cases of hepatic carcinomas, hemangiomas and adenomas were randomly selected at a same period for a comparative study.
RESULTS: There was a single focus in 22 cases and multiple foci in 3 cases. On the plain scan, 17 lesions showed hypodensity, 7 isodensity and 4 hyperdensity (the case with fatty liver). With contrast, 28 lesions were enhanced evenly or in the nodules in the arterial phase; 13 lesions still showed hyperdensity, 11 lesions isodensity and 4 lesions hypodensity in the parenchymatous phase; in the delayed phase only 5 lesions showed hyperdensity but 9 lesions showed isodensity or slight hypodensity and 14 lesions showed hypodensity. Twelve lesions of 28 had central asteroid scars. Thickened feeding arteries in postprocessing were seen in 24 lesions, and were integrated into the parenchymatous lesions with a gradual and smooth course. On the contrary, there were no artery penetrated into the lesion found in any of comparative hepatic tumors.
CONCLUSION: Doctors could make a correct diagnosis and differentiation of FNH on evaluation of the characteristic appearance on MSCT with postprocessing.
Angiography; Computer-assisted image processing; Focal nodular hyperplasia; Liver diseases; X-ray; Computed tomography
AIM: To investigate the mechanisms of how cyclooxygenase-2 (COX-2) regulates E-cadherin in gastric cancer cells.
METHODS: COX-2 expression in human gastric cancer cell lines SGC-7901, BGC-823, MGC-803 and AGS were measured at the mRNA and protein level. COX-2 rich cell line SGC-7901 was chosen for subsequent experiments. siRNA mediated gene knockdown was used to investigate the impact of COX-2 on nuclear factor-κB (NF-κB), Snail, and E-cadherin in gastric cancer cells. Gene expression was determined by Western blot and real-time polymerase chain reaction. To analyze whether NF-κB inhibition could interrupt the modulatory effect of COX-2 or prostaglandin E2 (PGE2) on E-cadherin, gastric cancer cells were treated with celecoxib or PGE2, in the presence of NF-κB specific siRNA.
RESULTS: Highest expression level of COX-2 was found in SGC-7901 cells, both at mRNA and protein levels. siRNA mediated down-regulation of COX-2 led to a reduced expression of NF-κB and Snail, but an increased expression of E-cadherin in SGC-7901 cells. siRNA mediated down-regulation of NF-κB also led to a reduced expression of E-cadherin and Snail in SGC-7901 cells. However, COX-2 expression did not alter after cells were treated with NF-κB specific siRNA in SGC-7901 cells. Treatment of SGC-7901 cells with celecoxib led to a reduced expression of Snail but an increased expression of E-cadherin. In contrast, treatment of SGC-7901 cells with PGE2 led to an increased Snail and a decreased E-cadherin. However, siRNA-mediated knockdown of NF-κB partially abolished the effect of celecoxib and PGE2 on the regulation of E-cadherin and Snail in SGC-7901 cells.
CONCLUSION: COX-2 likely functions upstream of NF-κB and regulates the expression of E-cadherin via NF-κB/Snail signaling pathway in gastric cancer cells.
Cyclooxygenase-2; E-cadherin; celecoxib; Prostaglandin E2; Gastric cancer
AIM: To examine transforming growth factor-β1 (TGF-β1) promoter methylation in gastric cancer and to determine if Helicobacter pylori (H. pylori) or interleukin (IL)-1β could induce TGF-β1 hypermethylation in vitro.
METHODS: We examined the frequency and extent of TGF-β1 promoter methylation using methylation-specific PCR in the gastric tissues from 47 gastric cancer patients and 39 non-gastric cancer subjects. H. pylori infection was confirmed by a positive result from either a serological test, histological analysis or C13 urea breath test. GES-1 and MKN-45 cells co-cultured with H. pylori or treated with IL-1β for 12, 24 and 48 h in vitro tested the effects of H. pylori or IL-1β on TGF-β1.
RESULTS: Twenty-four/forty-seven (51%) cases of gastric cancer (GC) tissues showed TGF-β1 promoter methylation, 15/47 (31.9%) cases of matched non-cancerous gastric mucosa tissues from the GC patients, and 11/39 (28%) case of the normal gastric mucosa tissues from non-GC subjects showed TGF-β1 promoter methylation (51% vs 28%, P < 0.05). Significantly higher levels of methylation of TGF-β1 were found in the tumor tissues than in non-tumor tissues from GC patients (0.24 ± 0.06 vs 0.17 ± 0.04, P < 0.05) and normal gastric tissues from non-GC subjects (0.24 ± 0.06 vs 0.15 ± 0.03, P < 0.05). TGF-β1 methylation was found in 48.3% of H. pylori-positive gastric mucosal tissues whereas only 23.1% of H. pylori-negative gastric mucosal tissues showed TGF-β1 methylation (48.3% vs 23.1%, P < 0.05). IL-1β appeared to induce a dose-dependent methylation of TGF-β1 and the strongest methylation was observed in GES-1 cells treated with 2.5 ng/mL of IL-1β for 48 h. Further studies showed that pre-treatment of GES-1 cells with 20 ng/mL IL-1RA for 1 h could partially abolish the effect of IL-1β on TGF-β1 methylation. Infection of GES-1 cells by H. pylori was not found to induce significant TGF-β1 promoter methylation.
CONCLUSION: Our data revealed that TGF-β1 promoter is methylated in GC patients. IL-1β may be an important mediator for H. pylori induced gene methylation during GC development.
Transforming growth factor-β1; Interleukin-1β; Methylation; Helicobacter pylori; Gastric cancer
AIM: To investigate the prevalence of minimal hepatic encephalopathy (MHE) and to assess corresponding health-related quality of life (HRQoL) in hospitalized cirrhotic patients in China.
METHODS: This multi-center cross-sectional study included 16 teaching hospitals, which were members of “Hepatobiliary Cooperation Group, Society of Gastroenterology, Chinese Medical Association”, from different areas of China carried out between June and October in 2011. All the eligible hospitalized cirrhotic patients (n = 538) were required to complete triplicate number connection tests combined with one digit symbol test for diagnosing MHE. Patients’ clinical examination data were complemented by a modified questionnaire assessing HRQoL. Written informed consent was obtained from each patient.
RESULTS: Male was predominant (68.6%) in 519 patients who met the criteria of the study, with a mean age of 49.17 ± 11.02 years. The most common cause of liver cirrhosis was chronic hepatitis B (55.9%). The prevalence of MHE was 39.9% and varied by Child-Pugh-Classification score (CPC-A: 24.8%, CPC-B: 39.4% and CPC-C: 56.1%, P < 0.01). MHE (P < 0.01) and higher CPC scores (P < 0.01) were associated with a high HRQoL scores (reflecting poorer quality of life). The prevalence of MHE was proportionate to CPC (P = 0.01) and high quality of life scores (P = 0.01).
CONCLUSION: Hospitalized cirrhotic patients have a high prevalence of MHE that is proportionate to the degree of liver function and HRQoL impairment.
Minimal hepatic encephalopathy; Health-related quality of life; China; Child-Pugh Classification; Liver cirrhosis
AIM: To investigate Krüppel-like factor 8 (KLF8) expression in gastric cancer and its relationship with angiogenesis and prognosis of gastric cancer.
METHODS: One hundred and fifty-four patients with gastric cancer who underwent successful curative resection were retrospectively enrolled in the study. Fifty tumor-adjacent healthy gastric tissues (≥ 5 cm from the tumor margin) obtained during the original resection were randomly selected for comparative analysis. In situ expression of KLF8 and CD34 proteins were examined by immunohistochemistry. The intratumoral microvessel density (MVD) was determined by manually counting the immunostained CD34-positive endothelial cells in three consecutive high-magnification fields (× 200). The relationship between differential KLF8 expression and MVD was assessed using Spearman’s correlation coefficient test. χ2 test was performed to evaluate the effects of differential KLF8 expression on clinicopathologic factors. Kaplan-Meier and multivariate Cox survival analyses were used to assess the prognostic value of differential KLF8 expression in gastric cancer.
RESULTS: Significantly higher levels of KLF8 protein were detected in gastric cancer tissues than in the adjacent non-cancerous tissues (54.5% vs 34.0%, P < 0.05). KLF8 expression was associated with tumor size (P < 0.001), local invasion (P = 0.005), regional lymph node metastasis (P = 0.029), distant metastasis (P = 0.023), and tumor node metastasis (TNM) stage (P = 0.002), as well as the MVD (r = 0.392, P < 0.001). Patients with KLF8 positive expression had poorer overall survival (P < 0.001) and cancer-specific survival (P < 0.001) than those with negative expression. Multivariate analysis demonstrated that KLF8 expression independently affected both overall and cancer-specific survival of gastric cancer patients (P = 0.035 and 0.042, respectively).
CONCLUSION: KLF8 is closely associated with gastric tumor progression, angiogenesis and poor prognosis, suggesting it may represent a novel prognostic biomarker and therapeutic target for gastric cancer.
Gastric cancer; Krüppel-like factor 8; Angiogenesis; Prognosis
AIM: To investigate the effect of polydatin (PD), a resveratrol glucoside, on mast cell degranulation and anti-allergic activity.
METHODS: After the rats were orally sensitized with ovalbumin (OVA) for 48 d and underwent PD treatment for 4 d, all the rats were stimulated by 100 mg/mL OVA for 24 h and then sacrificed for the following experiments. The small intestines from all the groups were prepared for morphology examination by hematoxylin and eosin staining. We also used a smooth muscle organ bath to evaluate the motility of the small intestines. The OVA-specific immunoglobulin E (IgE) production and interleukin-4 (IL-4) levels in serum or supernatant of intestinal mucosa homogenates were analyzed by enzyme-linked immunosorbent assay (ELISA). Using toluidine blue stain, the activation and degranulation of isolated rat peritoneal mast cells (RPMCs) were analyzed. Release of histamine from RPMCs was measured by ELISA, and regulation of PD on intracellular Ca2+ mobilization was investigated by probing intracellular Ca2+ with fluo-4 fluorescent dye, with the signal recorded and analyzed.
RESULTS: We found that intragastric treatment with PD significantly reduced loss of mucosal barrier integrity in the small intestine. However, OVA-sensitization caused significant hyperactivity in the small intestine of allergic rats, which was attenuated by PD administration by 42% (1.26 ± 0.13 g vs OVA 2.18 ± 0.21 g, P < 0.01). PD therapy also inhibited IgE production (3.95 ± 0.53 ng/mL vs OVA 4.53 ± 0.52 ng/mL, P < 0.05) by suppressing the secretion of Th2-type cytokine, IL-4, by 34% (38.58 ± 4.41 pg/mL vs OVA 58.15 ± 6.24 pg/mL, P < 0.01). The ratio of degranulated mast cells, as indicated by vehicles (at least five) around the cells, dramatically increased in the OVA group by 5.5 fold (63.50% ± 15.51% vs phosphate-buffered saline 11.15% ± 8.26%, P < 0.001) and fell by 65% after PD treatment (21.95% ± 4.37% vs OVA 63.50% ± 15.51%, P < 0.001). PD mediated attenuation of mast cell degranulation was further confirmed by decreased histamine levels in both serum (5.98 ± 0.17 vs OVA 6.67 ± 0.12, P < 0.05) and intestinal mucosa homogenates (5.83 ± 0.91 vs OVA 7.35 ± 0.97, P < 0.05). Furthermore, we demonstrated that administration with PD significantly decreased mast cell degranulation due to reduced Ca2+ influx through store-operated calcium channels (SOCs) (2.35 ± 0.39 vs OVA 3.51 ± 0.38, P < 0.01).
CONCLUSION: Taken together, our data indicate that PD stabilizes mast cells by suppressing intracellular Ca2+ mobilization, mainly through inhibiting Ca2+ entry via SOCs, thus exerting a protective role against OVA-sensitized food allergy.
Polydatin; Food allergy; Mast cells; Store-operated calcium channels; Ca2+
AIM: To investigate the benefits of probiotics treatment in septic rats.
METHODS: The septic rats were induced by cecal ligation and puncture. The animals of control, septic model and probiotics treated groups were treated with vehicle and mixed probiotics, respectively. The mixture of probiotics included Bifidobacterium longum, Lactobacillus bulgaricus and Streptococcus thermophilus. We observed the survival of septic rats using different amounts of mixed probiotics. We also detected the bacterial population in ascites and blood of experimental sepsis using cultivation and real-time polymerase chain reaction. The severity of mucosal inflammation in colonic tissues was determined.
RESULTS: Probiotics treatment improved survival of the rats significantly and this effect was dose dependent. The survival rate was 30% for vehicle-treated septic model group. However, 1 and 1/4 doses of probiotics treatment increased survival rate significantly compared with septic model group (80% and 55% vs 30%, P < 0.05). The total viable counts of bacteria in ascites decreased significantly in probiotics treated group compared with septic model group (5.20 ± 0.57 vs 9.81 ± 0.67, P < 0.05). The total positive rate of hemoculture decreased significantly in probiotics treated group compared with septic model group (33.3% vs 100.0%, P < 0.05). The population of Escherichia coli and Staphylococcus aureus in ascites of probiotics treated group were decreased significantly compared with that of septic model group (3.93 ± 0.73 vs 8.80 ± 0.83, P < 0.05; 2.80 ± 1.04 vs 5.39 ± 1.21, P < 0.05). With probiotics treatment, there was a decrease in the scores of inflammatory cell infiltration into the intestinal mucosa in septic animals (1.50 ± 0.25 vs 2.88 ± 0.14, P < 0.01).
CONCLUSION: Escherichia coli and Staphylococcus aureus may be primary pathogens in septic rats. Probiotics improve survival of septic rats by suppressing these conditioned pathogens.
Sepsis; Probiotics; Pathogens; Escherichia coli; Staphylococcus aureus
AIM: To investigate the expression and role of activin A in a mouse model of acute chemical liver injury.
METHODS: Acute liver injury in C57BL/6 male mice was induced by intraperitoneal injection with carbon tetrachloride (CCl4) (0.5 mL/kg, body weight) dissolved in olive oil (1:19 v/v). Mice were sacrificed 1, 3, 5 and 7 d after the treatment. The levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum were examined and pathological changes of liver observed by hematoxylin and eosin staining to evaluate the liver injury. Activin A protein levels in serum and hepatic tissue homogenate of mice were detected by enzyme-linked immunosorbent assay, and the expression pattern of activin A protein in livers of mice was examined by immunohistochemistry. Activin type IIA receptor (ActRIIA) and Smad3 expressions in the liver were analyzed by real-time quantitative reverse transcription-polymerase chain reaction. In order to further investigate the role of activin A, we also utilized activin A blocking experiment by anti-activin A antibody (500 μg/kg, body weight) injection into mouse tail vein.
RESULTS: In CCl4-treated mice, serum ALT and AST levels were significantly increased, compared with that in control mice (P < 0.01). Furthermore, the serious necrosis was observed around hepatic portal areas in CCl4-treated mice. Simultaneously, activin A levels in serum and hepatic tissue homogenate of mice treated with CCl4 for 1, 3 and 5 d increased significantly, compared with that in control mice (P < 0.01). Activin A protein expression in hepatocytes not within the necrotic area was also upregulated in mice following CCl4 treatment. Not only activin A, but also ActRIIA and activin signaling molecule Smad3 mRNA expressions in injury liver induced by CCl4 were significantly higher than that in control liver. In addition, levels of serum ALT and AST in CCl4-treated mice were significantly decreased by injection of anti-activin A antibody to block endogenous activin A action, compared with that in CCl4-treated mice by injection of immunoglobulin G instead of anti-activin A antibody (P < 0.01), and the severity of liver injury was also reduced remarkably.
CONCLUSION: These data show that activin A is involved in CCl4-induced acute liver injury. Blocking activin A actions may be a therapeutic approach for acute liver injury.
Liver injury; Carbon tetrachloride; Activin A; Immunohistochemistry
AIM: To investigate the effect of Danzhijiangtang capsule (DJC) on monocyte chemoattractant protein-1 (MCP-1) mRNA expression in newly diagnosed type 2 diabetes mellitus (T2DM) subclinical vascular lesions.
METHODS: Sixty-two patients with newly diagnosed T2DM subclinical vascular lesions were randomly divided into a control group and treatment group of 31 cases each. Oral antidiabetic therapy with routine western medicine was conducted in both groups, and the treatment group was additionally treated with DJCs. The treatment course for both groups was 12 wk. Before and after treatment, the total efficiency and traditional Chinese medicine (TCM) syndrome score were calculated. The fasting plasma glucose (FPG), 2-h plasma glucose (2hPG), fasting insulin (FINS), insulin resistance index (IRI), hemoglobin (Hb)A1c, blood lipids, and hemorheology indices were determined. In addition, the levels of vascular endothelial growth factors including thrombomodulin (TM), von Willebrand factor (vWF), P-selectin and MCP-1 mRNA were determined.
RESULTS: After 12 wk of treatment, the TCM syndrome score was significantly decreased compared to before treatment in both groups. After treatment, FPG, 2hPG, HbA1c, FINS, IRI, total cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein, whole blood low shear specific viscosity, plasma specific viscosity, TM, vWF, P-selectin and MCP-1 mRNA were significantly improved compared to before treatment in both groups. After treatment, the total efficiency and TCM syndrome score in the treatment group were better than in the control group. FINS, IRI, whole blood high shear specific viscosity, plasma specific viscosity, TM, vWF, P-selectin and MCP-1 mRNA level in the treatment group were significantly reduced after treatment compared with control group.
CONCLUSION: DJCs are efficacious in supplementing qi, nourishing yin and invigorating blood circulation, and upregulate MCP-1 mRNA expression in patients with T2DM subclinical vascular lesions.
Danzhijiangtang capsule; Type 2 diabetes mellitus; Subclinical vascular lesions; Monocyte chemoattractant protein-1
AIM: To investigate human epidermal growth factor receptor 2 (HER2) gene amplification and protein expression in Chinese patients with resectable gastric cancer and the association with clinicopathological characteristics and survival.
METHODS: One hundred and ninety-seven gastric cancer patients who underwent curative surgery procedures were enrolled into this study. HER2 gene amplification and protein expression were examined using fluorescence in-situ hybridization (FISH) and immunohistochemistry (IHC) analysis on formalin-fixed paraffin-embedded gastric cancer samples from all patients. For scoring, Hofmann’s HER2 gastric cancer scoring system was adopted. All cases showing IHC3+ or FISH positivity were defined as HER2 positive. Patient clinicopathological data and survival information were collected. Finally, χ2 statistical analysis was performed to analyze the HER2 positivity rate amongst the subgroups with different clinicopathological characteristics including; gender, age, tumor location, Lauren classification, differentiation, TNM staging, depth of invasion, lymph node metastases and distant metastasis. The probability of survival for different subgroups with different clinicopathological characteristics was calculated using the Kaplan-Meier method and survival curves plotted using log rank inspection.
RESULTS: According to Hofmann’s HER2 gastric cancer scoring criteria, 31 cases (15.74%) were identified as HER2 gene amplified and 19 cases (9.64%) were scored as strongly positive for HER2 membrane staining (3+), 25 cases (12.69%) were moderately positive (2+) and 153 cases (77.66%) were HER2 negative (0/1+). The concordance rate between IHC and FISH analyses was 88.83% (175/197). Thirty-six cases were defined as positive for HER2 gene amplification and/or protein expression, with 24 of these cases being eligible for Herceptin treatment according to United States recommendations, and 29 of these cases eligible according to EU recommendations. Highly consistent results were detected between IHC3+, IHC0/1 and FISH (73.68% and 95.42%), but low consistency was observed between IHC2+ and FISH (40.00%). The positivity rates in intestinal type and well-differentiated gastric cancer were higher than those in diffuse/mixed type and poorly-differentiated gastric cancer respectively (28.57% vs 13.43%, P = 0.0103; 37.25% vs 11.64%, P < 0.0001), but were not correlated with gender, age, tumor location or TNM stage, depth of invasion, lymph node metastases and distant metastasis. In poorly-differentiated gastric cancer patients, those without lymph node metastasis showed a higher HER2 positivity rate than those with lymph node metastasis (26.47% vs 7.14%, P = 0.0021). This association was not present in those patients with well-differentiated gastric cancer (28.57% vs 43.33%, P = 0.2832). Within our patient cohort, 26 cases were lost to follow-up. The median survival time for the remaining 171 patients was 18 mo. The median survival times of the HER2 positive and negative groups were 17 and 18.5 mo respectively. Overall survival was not significantly different between HER2-positive and negative groups (χ2 = 0.9157, P = 0.3386), but in patients presenting well-differentiated tumors, the overall survival of the HER2-positive group was significantly worse than that of the HER2-negative group (P = 0.0123). In contrast, patients with poorly differentiated and diffuse/mixed subtype gastric cancers showed no significant differences in overall survival associated with HER2. Furthermore, the median survival time of the HER2 positive group did not show any statistically significant differences when compared to the subgroups of gender, age, tumor location, TNM classification, lymph node metastases and distant metastasis.
CONCLUSION: Patients with intestinal type gastric cancer (GC), well-differentiated GC and poorly-differentiated GC without lymph node metastasis, may all represent suitable candidates for targeted therapy using Herceptin.
Gastric cancer; Human epidermal growth factor receptor 2; Gene amplification; Protein expression; Clinicopathological characteristics
AIM: To assess the diagnostic value of a combination of intragastric bile acids and hepatobiliary scintigraphy in the detection of duodenogastric reflux (DGR).
METHODS: The study contained 99 patients with DGR and 70 healthy volunteers who made up the control group. The diagnosis was based on the combination of several objective arguments: a long history of gastric symptoms (i.e., nausea, epigastric pain, and/or bilious vomiting) poorly responsive to medical treatment, gastroesophageal reflux symptoms unresponsive to proton-pump inhibitors, gastritis on upper gastrointestinal (GI) endoscopy and/or at histology, presence of a bilious gastric lake at > 1 upper GI endoscopy, pathologic 24-h intragastric bile monitoring with the Bilitec device. Gastric juice was aspirated in the GI endoscopy and total bile acid (TBA), total bilirubin (TBIL) and direct bilirubin (DBIL) were tested in the clinical laboratory. Continuous data of gastric juice were compared between each group using the independent-samples Mann-Whitney U-test and their relationship was analysed by Spearman’s rank correlation test and Fisher’s linear discriminant analysis. Histopathology of DGR patients and 23 patients with chronic atrophic gastritis was compared by clinical pathologists. Using the Independent-samples Mann-Whitney U-test, DGR index (DGRi) was calculated in 28 patients of DGR group and 19 persons of control group who were subjected to hepatobiliary scintigraphy. Receiver operating characteristic curve was made to determine the sensitivity and specificity of these two methods in the diagnosis of DGR.
RESULTS: The group of patients with DGR showed a statistically higher prevalence of epigastric pain in comparison with control group. There was no significant difference between the histology of gastric mucosa with atrophic gastritis and duodenogastric reflux. The bile acid levels of DGR patients were significantly higher than the control values (Z: TBA: -8.916, DBIL: -3.914, TBIL: -6.197, all P < 0.001). Two of three in the DGR group have a significantly associated with each other (r: TBA/DBIL: 0.362, TBA/TBIL: 0.470, DBIL/TBIL: 0.737, all P < 0.001). The Fisher’s discriminant function is followed: Con: Y = 0.002TBA + 0.048DBIL + 0.032TBIL - 0.986; Reflux: Y = 0.012TBA + 0.076DBIL + 0.089TBIL - 2.614. Eighty-four point zero five percent of original grouped cases were correctly classified by this method. With respect to the DGR group, DGRi were higher than those in the control group with statistically significant differences (Z = -5.224, P < 0.001). Twenty eight patients (59.6%) were deemed to be duodenogastric reflux positive by endoscopy, as compared to 37 patients (78.7%) by hepatobiliary scintigraphy.
CONCLUSION: The integrated use of intragastric bile acid examination and scintigraphy can greatly improve the sensitivity and specificity of the diagnosis of DGR.
Duodenogastric reflux; Diagnosis; Intragastric bile acids; Hepatobiliary scintigraphy
AIM: To compare effects of different resuscitation fluid on microcirculation, inflammation, intestinal barrier and clinical results in severe acute pancreatitis (SAP).
METHODS: One hundred and twenty patients with SAP were enrolled at the Pancreatic Disease Institute between January 2007 and March 2010. The patients were randomly treated with normal saline (NS group), combination of normal saline and hydroxyethyl starch (HES) (SH group), combination of normal saline, hydroxyethyl starch and glutamine (SHG group) in resuscitation. The ratio of normal saline to HES in the SH and SHG groups was 3:1. The glutamine (20% glutamine dipeptide, 100 mL/d) was supplemented into the resuscitation liquid in the SHG group. Complications and outcomes including respiratory and abdominal infection, sepsis, abdominal hemorrhage, intra-abdominal hypertension, abdominal compartment syndrome (ACS), renal failure, acute respiratory distress syndrome (ARDS), multiple organ dysfunction syndrome (MODS), operation intervention, length of intensive care unit stay, length of hospital stay, and mortality at 60 d were compared. Moreover, blood oxygen saturation (SpO2), gastric intramucosal pH value (pHi), intra-abdominal pressure (IAP), inflammation cytokines, urine lactulose/mannitol (L/M) ratio, and serum endotoxin were investigated to evaluate the inflammatory reaction and gut barrier.
RESULTS: Compared to the NS group, patients in the SH and SHG groups accessed the endpoint more quickly (3.9 ± 0.23 d and 4.1 ± 0.21 d vs 5.8 ± 0.25 d, P < 0.05) with less fluid volume (67.26 ± 28.53 mL/kg/d, 61.79 ± 27.61 mL/kg per day vs 85.23 ± 21.27 mL/kg per day, P < 0.05). Compared to the NS group, incidence of renal dysfunction, ARDS, MODS and ACS in the SH and SHG groups was obviously lower. Furthermore, incidence of respiratory and abdominal infection was significantly decreased in the SH and SHG groups, while no significant difference in sepsis was seen. Moreover, less operation time was needed in the SH and SHG group than the NS group, but the difference was not significant. The mortality did not differ significantly among these groups. Blood SpO2 and gastric mucosal pHi in the SH and SHG groups increased more quickly than in the NS group, while IAP was significantly decreased in the SH and SHG group. Moreover, the serum tumor necrosis factor-α, interleukin-8 and C-reactive protein levels in the SH and SHG groups were obviously lower than in the NS group at each time point. Furthermore, urine L/M ratio and serum endotoxin were significantly lower in the SH group and further decreased in the SHG group.
CONCLUSION: Results indicated that combination of normal saline, HES and glutamine are more efficient in resuscitation of SAP by relieving inflammation and sustaining the intestinal barrier.
Microcirculation; Intestinal barrier; Inflammatory reaction; Intra-abdominal hypertension; Capillary leakage syndrome
AIM: To investigate the normal hepatic magnetic resonance spectroscopy findings choline/lipid2 (Cho/Lip2) associated with age and body mass index (BMI).
METHODS: A total of 58 single-voxel proton spectra of the liver were acquired at 3.0 T using the eight-channel phased array abdominal coil as the receiver coil. Consecutive stacks of breath-hold spectra were acquired using the point resolved spectroscopy technique at a short echo time of 30 ms and a repetition time of 1500 ms. The spectra were processed with the SAGE software package. Areas and heights for metabolite resonance were obtained. Student’s t test for unpaired data was used for comparisons of shimming, Cho/Lip2, and lipid content.
RESULTS: There were significant negative correlations between the Cho/Lip2 peak height ratios and BMI (r = -0.615) and age (r = -0.398) (all P < 0.01). Compared with the high-BMI group, the low-BMI group was younger (39.1 ± 13.0 years vs 47.6 ± 8.5 years, t = -2.954, P = 0.005); had better water suppression (93.4% ± 1.4% vs 85.6% ± 11.6%, t = 2.741, P = 0.014); had higher Cho/Lip2 peak heights ratio (0.2 ± 0.14 vs 0.05 ± 0.04, t = 6.033, P < 0.000); and had lower lipid content (0.03 ± 0.08 vs 0.29 ± 0.31, t = -3.309, P = 0.004). Compared with the older group, the younger group had better shimming effects (17.1 ± 3.6 Hz vs 22.0 ± 6.8 Hz, t = -2.919, P = 0.008); higher Cho/Lip2 peak heights ratios (0.03 ± 0.05 vs 0.09 ± 0.12, t = 2.4, P = 0.020); and lower lipid content (0.05 ± 0.11 vs 0.23 ± 0.32, t = -2.337, P = 0.031). Compared with the low-choline peak group, the high-choline peak group had lower lipid content (0.005 ± 0.002 vs 0.13 ± 0.23, t = -3.796, P < 0.000); lower BMI (19.6 ± 2.4 vs 23.9 ± 3.0, t = -4.410, P < 0.000); and younger age (34.7 ± 10.0 years vs 43.2 ± 12.5 years, t = -2.088, P = 0.041).
CONCLUSION: Lipid accumulation could result from the increased fat in the body depending on age and BMI. Lipid can mask the resonance signal of choline.
Magnetic resonance spectroscopy; High-field imaging; Choline
AIM: To evaluate the safety and efficacy of granulocyte-colony stimulating factor (G-CSF) therapy in patients with hepatitis B virus (HBV)-associated acute-on-chronic liver failure (ACLF).
METHODS: Fifty-five patients with HBV-associated ACLF were randomized into two groups: the treatment group and the control group. Twenty-seven patients in the treatment group received G-CSF (5 μg/kg per day, six doses) treatment plus standard therapy, and 28 patients in the control group received standard therapy only. The peripheral CD34+ cell count was measured consecutively by flow cytometry. Circulating white blood cell count, biochemical parameters, and other clinical data of these patients were recorded and analyzed. All patients were followed up for a period of 3 mo to evaluate the changes in liver function and survival rate.
RESULTS: The peripheral neutrophil and CD34+ cell counts in the G-CSF group increased on day 3 from the onset of therapy, continued to rise on day 7, and remained elevated on day 15 compared to those of the control group. Child-Turcotte-Pugh score of patients in the treatment group was improved on day 30 from the onset of G-CSF therapy, compared to that in the controls (P = 0.041). Model for End-Stage of Liver Disease score of patients in the treatment group was improved on day 7 (P = 0.004) and remained high on day 30 from the onset of G-CSF therapy (P < 0.001) compared to that in controls. After 3 mo of follow-up observation, the survival rate in the treatment group (48.1%) was significantly higher than that in the control group (21.4%) (P = 0.0181).
CONCLUSION: G-CSF therapy promoted CD34+ cell mobilization in patients with HBV-associated ACLF, and improved the liver function and the survival rate of these patients.
Acute-on-chronic liver failure; Granulocyte-colony stimulating factor; Hepatitis B virus
AIM: To assess the usefulness of contrast-enhanced ultrasound (CEUS) during follow-up after percutaneous ablation therapy for hepatocellular carcinoma (HCC).
METHODS: A total of 141 patients with HCCs who received percutaneous ablation therapy were assessed by paired follow-up CEUS and contrast-enhanced computed tomography (CECT). The follow-up scheme was designed prospectively and the intervals between CEUS and CECT examinations were less than 14 d. Both images of follow-up CEUS and CECT were reviewed by radiologists. The ablated lesions were evaluated and classified as local tumor progression (LTP) and LTP-free. LTP was defined as regrowth of tumor inside or adjacent to the successfully treated nodule. The detected new intrahepatic recurrences were also evaluated and defined as presence of intrahepatic new foci. On CEUS and CECT, LTP and new intrahepatic recurrence both were displayed as typical enhancement pattern of HCC (i.e., hyper-enhancing during the arterial phase and washout in the late phase). With CECT as the reference standard, the ability of CEUS in detecting LTP or new intrahepatic recurrence during follow-up was evaluated.
RESULTS: During a follow-up period of 1-31 mo (median, 4 mo), 169 paired CEUS and CECT examinations were carried out for the 141 patients. For a total of 221 ablated lesions, 266 comparisons between CEUS and CECT findings were performed. Thirty-three LTPs were detected on CEUS whereas 40 LTPs were detected on CECT, there was significant difference (P < 0.001). In comparison with CECT, the numbers of false positive and false negative LTPs detected on CEUS were 6 and 13, respectively; the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and overall accuracy of CEUS in detecting LTPs were 67.5%, 97.4%, 81.8%, 94.4% and 92.3%, respectively. Meanwhile, 131 new intrahepatic recurrent foci were detected on CEUS whereas 183 were detected on CECT, there was also significant difference (P < 0.05). In comparison with CECT, the numbers of false positive and false negative intrahepatic recurrences detected on CEUS were 13 and 65, respectively; the sensitivity, specificity, PPV, NPV and overall accuracy of CEUS in detecting new intrahepatic recurrent foci were 77.7%, 92.0%, 92.4%, 76.7% and 84.0%, respectively.
CONCLUSION: The sensitivity of CEUS in detecting LTP and new intrahepatic recurrence after percutaneous ablation therapy is relatively low in comparison with CECT.
Contrast-enhanced ultrasound; Contrast-enhanced computed tomography; Hepatocellular carcinoma; Radiofrequency ablation; Microwave ablation
Left supraclavicular lymph node metastasis is a rare presentation of hepatocellular carcinoma (HCC). This phenomenon is easily neglected in the clinic. A 56-year-old man presented with HCC. On examination, a 1cm long left supraclavicular lymph node was palpated. Auxiliary examination indicated a lesion located in the right lobe of the liver. Fine needle aspiration cytology (FNAC) of the enlarged lymph node was performed; however, only necrosis was found. Hepatectomy was performed and HCC was confirmed by Hematoxylin-Eosin staining. However, 14 d after surgery, significantly enlarged left supraclavicular lymph nodes, a new intrahepatic lesion, and pulmonary and mediastinal metastasis appeared. An excisional biopsy of the left supraclavicular lymph node was performed, and its findings confirmed metastatic HCC. The patient’s HCC rapidly progressed and he died one month later. It is possible for HCC to metastasize to the left supraclavicular lymph node. Surgeons should always consider an overall physical examination. When left supraclavicular lymphadenopathy of unknown origin is encountered, FNAC should be performed initially. If the results are negative, an excisional biopsy and subsequent Positron emission tomography - computed tomography scanning should be performed. These are very important for making the correct diagnosis and for selecting reasonable therapies.
Left supraclavicular lymph node; Metastasis; Hepatocellular carcinoma; Fine needle aspiration cytology; Misdiagnosis
AIM: To compare the efficacy of modified percutaneous transhepatic variceal embolization (PTVE) with 2-octyl-cyanoacrylate (2-OCA) and endoscopic variceal obturation (EVO) with an injection of 2-OCA for prophylaxis of gastric variceal rebleeding.
METHODS: In this retrospective study, the medical records of liver cirrhosis patients with gastric variceal bleeding who underwent either endoscopic 2-OCA (EVO) or modified PTVE using 2-OCA at Shandong Provincial Hospital from January 2006 to December 2008 were reviewed. Patient demographics, rebleeding rate, survival rate, and complications were compared between the two groups (PTVE and EVO). All results were expressed as mean ± SD, or as a percentage. Quantitative variables were compared by two sample Student t tests, and qualitative variables were compared by the Fisher exact test or the χ2 test (with Yates correction) where appropriate. A P value less than 0.05 was considered significant. Statistical computation was performed using SPSS 13.0 software.
RESULTS: A total of 77 patients were included; 45 patients who underwent EVO and 32 patients who received PTVE. During the follow-up (19.78 ± 7.70 mo in the EVO group, vs 21.53 ± 8.56 mo in the PTVE group) rebleeding occurred in 17 patients in the EVO group and in 4 patients in the PTVE group (37.78% vs 12.5%, P = 0.028). The cumulative rebleeding-free rate was 75%, 59%, and 49% in 1, 2, and 3 years respectively for EVO, and 93%, 84%, and 84% for PTVE (P = 0.011). Cox analysis was used to identify independent factors that predicted rebleeding after treatment. Variables including age, gender, cause, Child-Pugh classification, size of gastric varices (GV), location of GV, and treatment methods were analyzed. It was revealed that Child-Pugh classification [risk ratio (RR) 2.10, 95%CI: 1.03-4.28, P = 0.040], choice of treatment (RR 0.25, 95%CI: 0.08-0.80, P = 0.019), and size of GV (RR 2.14, 95%CI: 1.07-4.28, P = 0.032) were the independent factors for predicting rebleeding. Follow-up computed tomography revealed that cyanoacrylate was retained in the varices and in the feeding veins of PTVE patients. During the follow-up, eight patients in the EVO group and four patients in the PTVE group died. The cumulative survival rates at 1, 2, and 3 years were 93%, 84%, and 67% respectively in the EVO group, and 97%, 88%, and 74% respectively in the PTVE group. The survival rates were not significantly different between the two groups (P = 0.432). Cox analysis showed that the Child-Pugh classification was the most significant prognostic factor of survival (RR 2.77, 95%CI: 1.12-6.80, P = 0.027). The incidence of complications was similar in both groups.
CONCLUSION: With extensive and permanent obliteration of gastric varices and its feeding veins, PTVE with 2-OCA is superior to endoscopic 2-OCA injection for preventing gastric variceal rebleeding.
Gastric varices; Endoscopic variceal obturation; Percutaneous transhepatic variceal embolization; 2-octyl-cyanoacrylate; Bleeding
AIM: To explore the optimal steroid therapeutic strategy for autoimmune pancreatitis (AIP).
METHODS: This study was conducted retrospectively in two large institutions in China. Patients with clinically, radiologically and biochemically diagnosed AIP were enrolled. The performed radiological investigations and biochemical tests, the regimen of the given steroid treatment, remission and relapse whether with and without steroid therapy were analyzed.
RESULTS: Twenty-eight patients with AIP received steroid treatment, while 40 patients were treated surgically by pancreatoduodenectomy, distal pancreatectomy and choledochojejunostomy, radiofrequency ablation for the enlarged pancreatic head, percutaneous transhepatic biliary drainage and endoscopic biliary drainage. The starting oral prednisolone dose was 30 mg/d in 18 (64.3%) patients and 40 mg/d in 10 (35.7%) patients administered for 3 wk. The remission rate of AIP patients with steroid treatment (96.4%) was significantly higher than in those without steroid treatment (75%). Maintenance therapy (oral prednisolone dose 5 mg/d) was performed after remission for at least 6-12 mo to complete the treatment course. Similarly, the relapse rate was significantly lower in AIP patients with steroid treatment (28.6%) than in those without steroid treatment (42.5%). Steroid re-treatment was effective in all relapsed patients with or without steroid therapy.
CONCLUSION: Steroid therapy should be considered in all patients with active inflammatory phase of AIP. However, the optimal regimen still should be trailed in larger numbers of patients with AIP.
Autoimmune pancreatitis; Chinese population; Steroid therapy; Remission; Relapse