PURPOSE: To find progression and prognosis of pancreatitis developed in massive burn patients through retrospective analysis. METHODS: A retrospective study was conducted on 32 patients with abnormal increase of serum lipase level among 2523 acute burn patients admitted to our burn center from January 1, 2017 to June 30, 2018. Pancreatitis in this study was defined as a serum lipase concentration level that is higher than 180 IU/L which is three times more than the normal level (less than 60 IU/L). In this study, a retrospective analysis was performed on patients with serum lipase level higher than 300 IU/L to better understand causality of burns and pancreatitis. RESULTS: 32 patients (1.27%) had serum lipase level higher than 180 IU/L among 2523 acute burn subjects. And 13 patients (0.52%) of these 32 patients had serum lipase level elevated more than 300 IU/L. The study indicated serum lipase level was increased around 7 days after the injury. It returned to normal level early as after 1 to 2 weeks and late as after 4 to 6 weeks of injury. The serum amylase level was increased as similar modality as to the serum lipase level increase. The serum bilirubin, AST, ALT, LD, and GGT were also observed to be elevated when serum lipase was more than 1000 IU/L. CONCLUSION: The pancreatitis developed in burn patients are mostly as mild symptom. It could due to the ischemic injury and can easily be treated by a temporary fasting, TPN, and Gabexate intravenous injection.
Amylases ; Bilirubin ; Burn Units ; Burns ; Fasting ; Gabexate ; Humans ; Injections, Intravenous ; Lipase ; Pancreatitis ; Prognosis ; Retrospective Studies

BACKGROUND/AIMS: This study investigated the protection provided by gabexate mesylate thermo-sensitive in-situ gel (GMTI) against grade III pancreatic trauma in rats. METHODS: A grade III pancreatic trauma model with main pancreatic duct dividing was established, and the pancreas anatomical diagram, ascites, and serum biochemical indices, including amylase, lipase, C-reactive protein (CRP), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α), were examined. The pancreas was sliced and stained with hematoxylin eosin and subjected to terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. RESULTS: Ascites, serum amylase, lipase, CRP, IL-6, and TNF-α levels were significantly increased in the pancreas trauma (PT) groups with prolonged trauma time and were significantly decreased after GMTI treatment. The morphological structure of the pancreas was loose, the acinus was significantly damaged, the nuclei were irregular and hyperchromatic, and there was inflammatory cell invasion in the PT group compared to the control. After GMTI treatment, the morphological structure of the pancreas was restored, and the damaged acinus and inflammatory cell invasion were decreased compared to the PT group. Moreover, the cell apoptosis index was significantly increased in the PT group and restored to the same levels as the control group after GMTI treatment. CONCLUSIONS: GMTI, a novel formulation and drug delivery method, exhibited specific effective protection against PT with acute pancreatitis therapy and has potential value as a minimally invasive adjuvant therapy for PT with acute pancreatitis.
Amylases ; Animals ; Apoptosis ; Ascites ; C-Reactive Protein ; DNA Nucleotidylexotransferase ; Eosine Yellowish-(YS) ; Gabexate* ; Hematoxylin ; Interleukin-6 ; Lipase ; Methods ; Necrosis ; Pancreas ; Pancreatic Ducts ; Pancreatitis ; Rats*

Gabexate mesilate (GM) is a trypsin inhibitor, and mainly used for treatment of various acute pancreatitis, including traumatic pancreatitis (TP), edematous pancreatitis, and acute necrotizing pancreatitis. However, due to the characteristics of pharmacokinetics, the clinical application of GM still needs frequently intravenous administration to keep the blood drug concentration, which is difficult to manage. Specially, when the blood supply of pancreas is directly damaged, intravenous administration is difficult to exert the optimum therapy effect. To address it, a novel thermosensitive in-situ gel of gabexate mesilate (GMTI) was developed, and the optimum formulation of GMTI containing 20.6% (w/w) P-407 and 5.79% (w/w) P188 with different concentrations of GM was used as a gelling solvent. The effective drug concentration on trypsin inhibition was examined after treatment with different concentrations of GMTI in vitro, and GM served as a positive control. The security of GMTI was evaluated by hematoxylin-eosin (HE) staining, and its curative effect on grade II pancreas injury was also evaluated by testing amylase (AMS), C-reactive protein (CRP) and trypsinogen activation peptide (TAP), and pathological analysis of the pancreas. The trypsin activity was slightly inhibited at 1.0 and 5.0 mg/mL in GM group and GMTI group, respectively (P<0.05 vs. P-407), and completely inhibited at 10.0 and 20.0 mg/mL (P<0.01 vs. P-407). After local injection of 10 mg/mL GMTI to rat leg muscular tissue, muscle fiber texture was normal, and there were no obvious red blood cells and infiltration of inflammatory cells. Furthermore, the expression of AMS, CRP and TAP was significantly increased in TP group as compared with control group (P<0.01), and significantly decreased in GM group as compared with TP group (P<0.01), and also slightly inhibited after 1.0 and 5.0 mg/mL GMTI treatment as compared with TP group (P<0.05), and significantly inhibited after 10.0 and 20.0 mg/mL GMTI treatment as compared with TP group (P<0.01). HE staining results demonstrated that pancreas cells were uniformly distributed in control group, and they were loosely arranged, partially dissolved, with deeply stained nuclei in TP group. Expectedly, after gradient GMTI treatment, pancreas cells were gradually restored to tight distribution, with slightly stained nuclei. This preliminary study indicated that GMTI could effectively inhibit pancreatic enzymes, and alleviate the severity of trauma-induced pancreatitis, and had a potential drug developing and clinic application value.
Amylases ; metabolism ; Animals ; C-Reactive Protein ; metabolism ; Delayed-Action Preparations ; chemical synthesis ; pharmacokinetics ; pharmacology ; Gabexate ; chemistry ; pharmacokinetics ; pharmacology ; Gels ; Male ; Muscle, Skeletal ; drug effects ; enzymology ; Oligopeptides ; metabolism ; Pancreas ; drug effects ; enzymology ; pathology ; Pancreatitis ; drug therapy ; enzymology ; etiology ; pathology ; Poloxamer ; chemistry ; Rats ; Rats, Sprague-Dawley ; Serine Proteinase Inhibitors ; chemistry ; pharmacokinetics ; pharmacology ; Temperature ; Wounds, Penetrating ; complications ; drug therapy ; enzymology ; pathology

OBJECTIVETo observe the effect of gut protease activity on visceral hypersensitivity in rats with acute restraint stress.

METHODSSprague-Dawley rats were given 30, 100 or 300 mg/kg camostat mesilate (CM), a protease inhibitor, or saline intragastrically 30 min before acute restraint stress induced by wrapping the fore shoulders, upper forelimbs and thoracic trunk for 2 h. Visceral perception of the rats was quantified as the visceral motor response with an electromyography, and the rectal mucosa and feces protease activity and spinal c-fos expression were measured.

RESULTSCM dose-dependently reduced visceral sensitization elicited by rectal distension, but these doses did not completely inhibit stress-induced visceral sensitization. In normal rats, c-fos expression was found mainly in the superal spinal cord dorsal horn, and after the administration the CM, c-fos-positive cells decreased significantly in all dose groups (P<0.05). In 30 mg/kg CM group, fecal and rectal mucosal protease activity significantly decreased as compared with that in the stress group (P<0.05), and as CM dose increased to 100 and 300 mg/kg, the protease activity decreased even further (P<0.01).

CONCLUSIONThe gut protease is involved in acute stress-induced visceral hypersensitivity, and CM can lower the visceral sensitivity and spinal c-fos expression in rats.

Animals ; Gabexate ; analogs & derivatives ; pharmacology ; Protease Inhibitors ; pharmacology ; Proto-Oncogene Proteins c-fos ; metabolism ; Rats ; Rats, Sprague-Dawley ; Restraint, Physical ; Spinal Cord ; metabolism ; Stress, Physiological

BACKGROUND/AIMS: Ciprofloxacin is considered to be a safe and effective treatment for acute infectious colitis. However, this drug may cause drug-induced pancreatitis, albeit rarely. METHODS: From March 2007 to February 2012, we studied 227 patients who were hospitalized for infectious colitis at St. Mary's Hospital. All of the patients received ciprofloxacin therapy for the treatment of infectious colitis. We observed a few cases of rare adverse events, including ciprofloxacin-induced acute pancreatitis diagnosed based on the Naranjo algorithm. RESULTS: During ciprofloxacin therapy, seven of 227 patients (3.1%) developed rare pancreatitis as defined by the Naranjo algorithm; pancreatic enzyme activity was sporadically elevated with ciprofloxacin use. After ciprofloxacin administration, the average interval until the development of pancreatitis was 5.5 days (range, 4 to 7 days). On abdominal computed tomography, pancreatic swelling and homogenous enhancement was noted in three of seven patients. Complicating acute pancreatitis was gradually but completely resolved after cessation of ciprofloxacin administration. The mean recovery time was 11.3 days (range, 8 to 15 days). CONCLUSIONS: We observed that ciprofloxacin-induced pancreatitis may occur with an incidence of approximately 3%. Ciprofloxacin-induced pancreatitis presents a short latency, suggesting an idiosyncratic hypersensitivity reaction. Practitioners should be aware that drug-induced pancreatitis can occur during ciprofloxacin therapy.
Acute Disease ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/*adverse effects ; Bacterial Infections/*drug therapy ; Ciprofloxacin/*adverse effects ; Colitis/*drug therapy ; Enzyme Inhibitors/therapeutic use ; Female ; Gabexate/analogs & derivatives/therapeutic use ; Humans ; Male ; Middle Aged ; Pancreatitis/*chemically induced/drug therapy ; Young Adult

BACKGROUND/AIMS: Acute pancreatitis is a common complication of endoscopic retrograde cholangiopancreatography (ERCP). Only a few pharmacologic agents have been shown to have potential efficacy for the prophylactic treatment of post-ERCP pancreatitis (PEP). The aim of this study was to determine whether prophylactic gabexate and ulinastatin can decrease the incidence of PEP. METHODS: From January 2005 to April 2010, 1,679 patients undergoing ERCP treatment were consecutively enrolled in the study. After selective exclusion, a total of 1,480 patients were included in the analysis. The patients were separated into 3 groups according to the prophylactic administration of gabexate (593 patients), ulinastatin (229 patients), or saline solution (658 patients) and analyzed retrospectively. The primary outcome measurements were the incidence of pancreatitis and hyperamylasemia. RESULTS: PEP occurred in 21 of the 593 (3.5%) patients who received gabexate, 16 of the 229 (7.0%) patients who received ulinastatin, and 48 of the 658 (7.3%) patients who received a saline solution. The incidence of PEP was significantly different between the gabexate and ulinastatin or saline solution groups (p<0.05). CONCLUSIONS: Gabexate prophylaxis is effective in preventing PEP. However, there is no difference in the beneficial effects of the prophylactic administration of ulinastatin and a saline solution.
Cholangiopancreatography, Endoscopic Retrograde ; Gabexate ; Glycoproteins ; Humans ; Incidence ; Oligopeptides ; Pancreatitis ; Retrospective Studies ; Sodium Chloride

BACKGROUND/AIMS: ERCP is the most common procedure for the diagnosis and treatment of bile duct and pancreatic disease, but Post-ERCP pancreatitis makes poor outcome in some cases. The protease inhibitors, nafamostat and gabexate, have been used to prevent pancreatitis related to ERCP, but there is some debate. We tried to evaluate the efficacy of gabexate and nafamostat for the prevention of post-ERCP pancreatitis. METHODS: Two hundred forty two patients (73 patients in the gabexate group, 88 patients in the nafamostat group and 81 patients in the placebo group) were included in the study after selective exclusion. The incidence of pancreatitis after ERCP was compared among groups. RESULTS: The incidence of pancreatitis were 6.8% in the gabexate group, 5.7% in the nafamostat group and 6.2% in the placebo group (p=0.954). CONCLUSIONS: There was no meaningful difference among the gabexate, nafamostat and placebo group.
Adult ; Aged ; Aged, 80 and over ; Cholangiopancreatography, Endoscopic Retrograde/*adverse effects ; Female ; Gabexate/*therapeutic use ; Guanidines/*therapeutic use ; Humans ; Male ; Middle Aged ; Pancreatitis/etiology/*prevention & control ; Placebo Effect ; Questionnaires ; Serine Proteinase Inhibitors/*therapeutic use ; Young Adult

BACKGROUNDPost-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) is regarded as one of the worrisome complications of endoscopic retrograde cholangiopancreatography (ERCP). Results of randomized controlled trials evaluating the preventive effect of ulinastatin and gabexate mesylate (GM) on PEP are contradictory. The present study was designed to evaluate the prophylactic effect of ulinastatin and GM on PEP with meta-analyses of randomized controlled trials (RCTs).

METHODSFive electronic databases were searched for RCTs evaluating the preventive effect of ulinastatin and GM on PEP. Summary effects were assessed with the methods recommended by the Cochrane Collaboration.

RESULTSTwelve studies involving 5105 participants were included in our meta-analyses. Administration of ulinastatin decreased the incidence of PEP only at sufficient doses (OR, 0.39; 95%CI, 0.19 to 0.81; P = 0.01). Number needed to treat (NNT) was 6. And administration of ulinastatin also reduced the incidence of post-ERCP hyperamylasemia (PEHA) (OR, 0.40; 95%CI, 0.28 to 0.58; P < 0.000 01). Slow infusion of high-dose GM was effective for PEP prevention (OR, 0.44; 95%CI, 0.25 to 0.79; P = 0.006), and rapid infusion of low-dose GM also showed efficacy for PEP prophylaxis (OR, 0.37; 95%CI, 0.20 to 0.69; P = 0.002). NNT was 7 and 6 respectively. However, administration of GM at low doses and by slow infusions was ineffective (OR, 0.99; 95%CI, 0.64 to 1.55; P = 0.98). Administration of GM had the tendency to reduce PEHA rate, but not to a statistical significance (OR, 0.86; 95%CI, 0.73 to 1.01; P = 0.06). When low-quality studies were excluded, the meta-analysis with two high-quality studies indicated that ulinastatin did not reduce the rate of PEP (OR, 0.63; 95%CI, 0.32 to 1.26; P = 0.19) and PEHA incidence (OR, 0.80; 95%CI, 0.31 to 2.07; P = 0.64). The meta-analysis with six high-quality studies showed that GM administration decreased PEP incidence (OR, 0.52; 95%CI, 0.29 to 0.91; P = 0.02), while was not efficacious for PEHA prevention (OR, 0.88; 95%CI, 0.74 to 1.04; P = 0.12).

CONCLUSIONSUlinastatin and GM may be of value for the prophylaxis of PEP. GM should be administered at high doses and by rapid infusions. And the doses of ulinastatin should be sufficient. However, the conclusions are not overwhelming. More large-sample size and high-quality RCTs are still needed to elucidate whether administrations of the two drugs really have prophylactic effect on PEP.

Cholangiopancreatography, Endoscopic Retrograde ; adverse effects ; Gabexate ; therapeutic use ; Glycoproteins ; therapeutic use ; Humans ; Pancreatitis ; prevention & control

Pancreaticopleural fistula is an uncommon complication of chronic pancreatitis. We report a case of pancreaticopleural fistula that was presented with right-sided hemothorax. A 49-year-old male with a history of chronic alcoholism was presented with a month of dyspnea. A chest radiography showed a right-sided massive pleural effusion with old-blood-colored fluids and amylase levels of 1,020 IU/L. On the chest computerized tomography (CT), there was pleural effusion and a well-defined tract from the posterior mediastinum to the pseudocyst in the tail of the pancreas. Even with conservative treatment with closed thoracostomy, octreotide and gabexate mesilate, he developed hemothorax. Abdominal CT revealed an increase of the hemorrhagic pancreatic pseudocyst. Distal pancreatectomy with splenectomy and external drainage of the pancreaticopleural fistula on the posterior mediasternum were performed. The patient had an uneventful course and was discharged on the 27th postoperative day. Management of pancreaticopleural fistula is multimodal included medication, endoscopic stenting and surgery. Surgery in pancreaticopleural fistula might be beneficial in selective cases.
Alcoholism ; Amylases ; Drainage ; Dyspnea ; Fistula ; Gabexate ; Hemothorax ; Humans ; Male ; Mediastinum ; Middle Aged ; Octreotide ; Pancreas ; Pancreatectomy ; Pancreatic Pseudocyst ; Pancreatitis, Chronic ; Pleural Effusion ; Splenectomy ; Stents ; Thoracostomy ; Thorax

BACKGROUND/AIMS: The protease inhibitors, nafamostat and gabexate, have been used to prevent pancreatitis related to endoscopic retrograde cholangiopancreatography (ERCP). In vitro, nafamostat inhibits the pancreatic protease activities 10-100 times more potently than gabexate. We evaluated the efficacy of nafamostat for prophylaxis against post-ERCP pancreatitis in comparison with gabexate. METHODS: Five hundred patients (208 patients in the nafamostat-treated group and 292 in the gabexate-treated group) were analyzed retrospectively after selective exclusion. The incidences of pancreatitis and hyperamylasemia after the ERCP were compared between the nafamostat and gabexate groups. RESULTS: The incidences of acute pancreatitis and hyperamylasemia were 9.1% and 40.9%, respectively, in the nafamostat-treated group, and 8.6% and 39.4% in the gabexate-treated group. The frequencies of post-ERCP pancreatitis and hyperamylasemia did not differ significantly between the two groups, Post-ERCP pancreatitis in two group did not vary according to the different ERCP procedures. The mean serum amylase level at 6 h after ERCP was significantly lower in the nafamostat-treated group than in the gabexate-treated group (p=0.020). However, the difference in serum amylase level did not persist at 18 h and 36 h post-ERCP. CONCLUSIONS: Administration of nafamostat before ERCP was not inferior to gabexate in protecting against the development of pancreatitis.
Amylases ; Cholangiopancreatography, Endoscopic Retrograde ; Gabexate ; Guanidines ; Humans ; Hyperamylasemia ; Incidence ; Pancreatitis ; Protease Inhibitors ; Retrospective Studies