Xiao-Nan Yang

Present and future of prophylactic antibiotics for severe acute pancreatitis

AIM To investigate the role of prophylactic antibiotics in the reduction of mortality of severe acute pancreatitis (SAP) patients, which is highly questioned by more and more randomized controlled trials (RCTs) and meta-analyses. METHODS An updated meta-analysis was performed. RCTs comparing prophylactic antibiotics for SAP with control or placebo were included for meta-analysis. The mortality outcomes were pooled for estimation, and re-pooled estimation was performed by the sensitivity analysis of an ideal large-scale RCT. RESULTS Currently available 11 RCTs were included. Subgroup analysis showed that there was significant reduction of mortality rate in the period before 2000, while no significant reduction in the period from 2000 [Risk Ratio, (RR) = 1.01, P = 0.98]. Funnel plot indicated that there might be apparent publication bias in the period before 2000. Sensitivity analysis showed that the RR of mortality rate ranged from 0.77 to 1.00 with a relatively narrow confidence interval (P < 0.05). However, the number needed to treat having a minor lower limit of the range (7-5096 patients) implied that certain SAP patients could still potentially prevent death by antibiotic prophylaxis. CONCLUSION Current evidences do not support prophylactic antibiotics as a routine treatment for SAP, but the potentially benefited sub-population requires further investigations.

Effect of antibiotic prophylaxis on acute necrotizing pancreatitis: Results of a randomized controlled trial

Background and Aims:  This study addresses whether antibiotic prophylaxis is beneficial for acute necrotizing pancreatitis.

Short-term continuous high-volume hemofiltration on clinical outcomes of severe acute pancreatitis.

Objectives This study aimed to conduct a single-center prospective trial of short-term continuous high-volume hemofiltration (HVHF) in patients with predicted severe acute pancreatitis (SAP). Methods Patients with acute pancreatitis with Acute Physiology and Chronic Health Evaluation II scores of greater than 15 on admission between January 2008 and December 2010 were allocated to receive either optimal standard therapy or 72 hours of continuous HVHF on an alternate basis, beginning as soon as possible after admission. Biomarkers and clinical outcomes were compared between the 2 groups. Results A total of 61 patients received either conventional therapy (n = 29) or HVHF (n = 32). High-volume hemofiltration treatment was associated with a significant reduction in the incidence of renal failure (P = 0.013), infected pancreatic necrosis (P = 0.048), length of hospitalization (P = 0.005), mortality (P = 0.033), as well as duration of renal (P < 0.001), respiratory (P = 0.002), and hepatic failure (P = 0.001). Acute Physiology and Chronic Health Evaluation II score and C-reactive protein and interleukin 6 levels were significantly reduced after the start of HVHF on days 1, 3, and 7 (all, P < 0.05). Conclusions This study suggests that short-term HVHF may reduce local and systemic complications and mortality in patients with SAP with Acute Physiology and Chronic Health Evaluation score of greater than 15.

Validation of the moderate severity category of acute pancreatitis defined by determinant-based classification

BACKGROUND Recent international multidisciplinary consultation proposed the use of local (sterile or infected pancreatic necrosis) and/or systemic determinants (organ failure) in the stratification of acute pancreatitis. The present study was to validate the moderate severity category by international multidisciplinary consultation definitions. METHODS Ninety-two consecutive patients with severe acute pancreatitis (according to the 1992 Atlanta classification) were classified into (i) moderate acute pancreatitis group with the presence of sterile (peri-) pancreatic necrosis and/or transient organ failure; and (ii) severe/critical acute pancreatitis group with the presence of sterile or infected pancreatic necrosis and/or persistent organ failure. Demographic and clinical outcomes were compared between the two groups. RESULTS Compared with the severe/critical group (n=59), the moderate group (n=33) had lower clinical and computerized tomographic scores (both P<0.05). They also had a lower incidence of pancreatic necrosis (45.5% vs 71.2%, P=0.015), infection (9.1% vs 37.3%, P=0.004), ICU admission (0% vs 27.1%, P=0.001), and shorter hospital stay (15+/-5 vs 27+/-12 days; P<0.001). A subgroup analysis showed that the moderate group also had significantly lower ICU admission rates, shorter hospital stay and lower rate of infection compared with the severe group (n=51). No patients died in the moderate group but 7 patients died in the severe/critical group (4 for severe group). CONCLUSIONS Our data suggest that the definition of moderate acute pancreatitis, as suggested by the international multidisciplinary consultation as sterile (peri-) pancreatic necrosis and/or transient organ failure, is an accurate category of acute pancreatitis.

Urinary trypsinogen-2 for diagnosing acute pancreatitis: a meta-analysis

BACKGROUND Currently, serum amylase and lipase are the most popular laboratory markers for early diagnosis of acute pancreatitis with reasonable sensitivity and specificity. Urinary trypsinogen-2 (UT-2) has been increasingly used but its clinical value for the diagnosis of acute pancreatitis and post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis has not yet been systematically assessed. DATA SOURCES A comprehensive search was carried out using PubMed (MEDLINE), Embase, and Web of Science for clinical trials, which studied the usefulness of UT-2 as a diagnostic marker for acute pancreatitis. Sensitivity, specificity and the diagnostic odds ratios (DORs) with 95% confidence interval (CI) were calculated for each study and were compared with serum amylase and lipase. Summary receiver-operating curves were conducted and the area under the curve (AUC) was evaluated. RESULTS A total of 18 studies were included. The pooled sensitivity and specificity of UT-2 for the diagnosis of acute pancreatitis were 80% and 92%, respectively (AUC=0.96, DOR=65.63, 95% CI: 31.65-139.09). The diagnostic value of UT-2 was comparable to serum amylase but was weaker than serum lipase. The pooled sensitivity and specificity for the diagnosis of post-ERCP pancreatitis were 86% and 94%, respectively (AUC=0.92, DOR=77.68, 95% CI: 24.99-241.48). CONCLUSIONS UT-2 as a rapid test could be potentially used for the diagnosis of post-ERCP pancreatitis and to an extent, acute pancreatitis. Further studies are warranted to confirm these results.

Chaiqinchengqi decoction regulates necrosis-apoptosis via regulating the release of mitochondrial cytochrome c and caspase-3 in rats with acute necrotizing pancreatitis

OBJECTIVE To explore the effect and the mechanism of Chaiqinchengqi decoction (CQCQD) on the apoptosis-necrosis switch of pancreatic acinar cells in acute necrotizing pancreatitis (ANP) in rats. METHODS Sixty Sprague-Dawley rats were randomized into the control group, the ANP group and the CQCQD group. The acute pancreatitis (AP) model was induced by intraperitoneal injections of 4 g/kg 8% L-Arginine (PH 7.0) twice with a 1 h interval. Rats in the CQCQD group were intragastrically administered CQCQD (20 mL/kg every 2 h, 3 times, then 20 mL/kg every 6 h, 3 times). Rats were killed at the 6 and 24 h after the induction of AP. The pancreatic tissues were collected for pathology and to isolate pancreatic acinar cells and mitochondria. RESULTS CQCQD significantly ameliorated the severity of ANP by reducing the pancreatic histopathology score, indicated by lactate dehydrogenase levels at the 6 and 24 h. The CQCQD group promoted the apoptosis of pancreatic acinar cells by raising the apoptosis index compared with the ANP group and the control group. Mitochondrial cytochrome c at the 6 and 24 h in the ANP group were lower than that in the control group or the CQCQD group (0.67 +/- 0.13 vs 1.54 +/- 0.03 vs 0.81 +/- 0.09; 0.71 +/- 0.08 vs 1.55 +/- 0.09 vs 0.89 +/- 0.16, P < 0.01). The cytochrome c levels in the cytoplasm at the 6 and 2 h in the CQCQD group were higher than in the control group (1.36 +/- 0.15 vs 0.67 +/- 0.04, 1.46 +/- 0.08 vs 0.59 +/- 0.09, P < 0.01), or the ANP group (0.96 +/- 0.13, P > 0.05; 0.97 +/- 0.09, P < 0.05). CQCQD increased caspase-3 activity over the ANP group at the 6 h. CONCLUSION CQCQD can induce apoptosis and relieve the necrosis of pancreatic acinar cells via promoting the release of mitochondrial cytochrome c and increasing pancreatic caspase-3 activity in ANP rats.

Serum matrix metalloproteinase-9 is an early marker of pancreatic necrosis in patients with severe acute pancreatitis.

BACKGROUND/AIMS To study the ability of matrix metalloproteinase-9 (MMP-9) to predict pancreatic necrosis (PN) in patients with severe acute pancreatitis (SAP). METHODOLOGY From July 1, 2010 to December 31, 2010 patients diagnosed with SAP were included (n=35). Serum MMP-9, CRP and IL-6 were analyzed on days 1, 3, 5 and 7 of hospitalization to determine if they could predict the development of pancreatic necrosis. RESULTS Of the 35 patients included, 12 (34.3%) had evidence of PN. Admission MMP-9 concentrations were significantly higher in patients with PN compared to subjects without PN (13.1±4.0 vs. 7.5±3.8, p<0.05). Receiver operating characteristic curves for PN revealed an area under the curve of 0.832 for admission MMP-9 (95% confidence interval 0.696-0.967, p=0.001). Elevated concentrations of MMP-9 on admission for pancreatic necrosis =9.35mg/L yielded a positive predictive value of 90.9% with a sensitivity of 91.7% and a specificity of 69.6%. Binary logistic regression indicated that MMP-9 was significantly associated with pancreatic necrosis (Odds ratios 25.1, 95% confidence interval 2.7-234.2; p=0.005). CONCLUSIONS An elevation in serum MMP-9 within the first 24 hours of disease is strongly associated with the development of pancreatic necrosis. This finding may have important clinical implications and requires further investigation.

Circulating microRNA 216 as a Marker for the Early Identification of Severe Acute Pancreatitis

Background: To study the value of circulating microRNA 216 (miR‐216) as a marker for the severity of acute pancreatitis (AP) in both murine models and patients. Materials and Methods: Mice with AP were induced by intraperitoneal injection of 50 &mgr;g/kg/hour cerulean either 7 times, sacrificed at 8, 9, 10, 11 or 12 hours after the first injection, or 12 times, sacrificed at 24 hours after the first injection. Plasma samples and data from patients with AP were obtained from a prospective cohort. Quantitative reverse transcription polymerase chain reaction was used to determine the miR‐216a and miR‐216b level. Results: The upregulation of miR‐216a and miR‐216b in the serum of mice was induced by cerulean injection in both the 7‐ and 12‐injection groups (P < 0.05). The downregulation of miR‐216a in pancreatic tissues of mice with AP was detected (P < 0.05), but no difference was observed in pancreatic miR‐216b levels among any of the groups (all P > 0.05). The serum miR‐216a level was positively correlated with pancreatic histopathology severity scores, and was negatively correlated with pancreatic miR‐216a (r = −0.483, P = 0.009). The plasma miR‐216a level was significantly upregulated in patients with severe AP (SAP) compared with patients with mild AP (MAP) or moderate severe AP (MSAP) (SAP versus MAP, P = 0.04; SAP versus MSAP, P = 0.00), but no difference was seen between patients with MAP and those with MSAP (P = 0.73). Conclusions: Circulating miR‐216a might be a potential biomarker for the early identification of SAP.

Changes of neuronal acetylcholine receptor alpha 7 of peritoneal macrophage in experimental acute pancreatitis treated by Chaiqin Chengqi Decoction (柴芩承气汤)

ObjectiveTo investigate effect of Chaiqin Chengqi Decoction (柴芩承气汤, CQCQD) on changes of neuronal acetylcholine receptor alpha 7 (nAChRα7) of peritoneal macrophages in acute pancreatitis (AP).MethodsEighteen Kunming mice were equally randomized into the control group, AP group and CQCQD treatment group. AP was induced by two intraperitoneal injections of 4 g/kg L-arginine at 1 h apart, while control mice received saline injections. At 72 h after the first injection of L-arginine, mice in the treatment group were intragastrically administered 0.1 mL/10 g CQCQD every 2 h for 3 times, whilst mice in the other two groups received the same amount of saline feeding. Mice were sacrificed by cervical dislocation 2 h after the last feeding of either CQCQD or saline. Peritoneal macrophages were collected for determination of nAChRα7 mRNA and protein expression. Serum was collected for detection of interleukin-6 (IL-6), IL-10 and acetylcholine (ACh) levels, and pancreas was for histopathology analysis.ResultsThe CQCQD treatment significantly ameliorated the severity of AP as evidenced by reducing the pancreatic histopathology score (4.5±0.5 vs. 6.2±1.7, P<0.05) and the serum IL-6 levels (1228.3±419.2 pg/mL vs. 1589.6±337.3 pg/mL, P<0.05). The mRNA and protein expression of nAChRα7 of the peritoneal macrophages in the AP group were similar to the control group (P>0.05), but were significantly up-regulated after the CQCQD treatment (P<0.05). The serum ACh levels in the AP group were significantly lower than those in the control group (3.1±0.6 μg/mL vs 4.8±0.7 μg/mL P<0.05), but were significantly increased after the CQCQD treatment (5.6±1.5 μg/mL vs 3.1±0.6 μg/mL, P<0.05).ConclusionCQCQD is protective against L-arginine-induced AP through mechanisms involving nAChRα7 of peritoneal macrophages.

The effect of Chaiqin Chengqi Decoction (柴芩承气汤) on modulating serum matrix metalloproteinase 9 in patients with severe acute pancreatitis

ObjectiveTo investigate the effect of Chaiqin Chengqi Decoction (柴芩承气汤, CQCQD) on regulating serum matrix metalloproteinase 9 (MMP-9) in patients with severe acute pancreatitis (SAP).MethodsThirty-five SAP patients hospitalized in West China Hospital from September 1, 2008 to February 28, 2009 were randomly assigned to two groups using a computer-derived random number sequence in a ratio of 1:1, treatment group (18 patients) and the placebo control group (17 patients). The patients in the treatment group were administered with CQCQD by gastric perfusion (50 mL/2 h) and retention enema (200 mL/6 h) for 7 days. The two groups had similar baseline information. The clinical indicators, including the initial Balthazar’s computed tomography (CT) score, acute physiology and chronic health evaluation II (APACHE II) scores on 1st, 3rd, 5th and 7th day, incidences and durations of complications and the serum C-reactive protein (CRP), levels of MMP-9 on the 1st, 3rd, 5th and 7th day, were recorded and compared between the two groups.ResultsThe serum MMP-9, CRP and the APACHE II scores on the 3rd, 5th and 7th day in the treatment group were lower than those in the control group (P<0.05). The serum MMP-9 was positively correlated with the APACHE II score on the 1st day (r=0.430, P=0.01). The durations of acute respiratory distress syndrome (5.4±2.4 vs. 2.9±1.3), acute hepatitis (4.6±0.8 vs. 1.9±0.6) and acute heart failure (3.9±1.6 vs. 1.3±0.6, <0.05) in the control group were longer than those in the treatment group.ConclusionCQCQD could decrease the serum MMP-9 to relieve the severity of clinical symptoms and prevent the development of multiple organ dysfunction syndrome in patients with SAP.