The Clinical Investigation Study of Pancreatitis Developed in Burn Patients

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.

Protection Provided by a Gabexate Mesylate Thermo-Sensitive In Situ Gel for Rats with Grade III Pancreatic Trauma

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.

A novel thermosensitive in-situ gel of gabexate mesilate for treatment of traumatic pancreatitis: An experimental study / 华中科技大学学报（医学）（英德文版）

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.

Acute Pancreatitis Secondary to Ciprofloxacin Therapy in Patients with Infectious Colitis

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.

Camostat mesilate, a protease inhibitor, inhibits visceral sensitivity and spinal c-fos expression in rats with acute restraint stress / 南方医科大学学报

<p><b>OBJECTIVE</b>To observe the effect of gut protease activity on visceral hypersensitivity in rats with acute restraint stress.</p><p><b>METHODS</b>Sprague-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.</p><p><b>RESULTS</b>CM 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).</p><p><b>CONCLUSION</b>The gut protease is involved in acute stress-induced visceral hypersensitivity, and CM can lower the visceral sensitivity and spinal c-fos expression in rats.</p>

The Use of Gabexate Mesylate and Ulinastatin for the Prevention of Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis

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.

Could Nafamostat or Gabexate Prevent the Post Endoscopic Retrograde Cholangiopancreatography Pancreatitis? / 대한소화기학회지

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.

Preventive effect of ulinastatin and gabexate mesylate on post-endoscopic retrograde cholangiopancreatography pancreatitis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Post-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).</p><p><b>METHODS</b>Five 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.</p><p><b>RESULTS</b>Twelve 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).</p><p><b>CONCLUSIONS</b>Ulinastatin 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.</p>

Pancreaticopleural Fistula with Hemothorax

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.

Nafamostat for Prophylaxis against Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis Compared with Gabexate

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.

Clinical trial of gabexate in the prophylaxis of post-endoscopic retrograde cholangiopancreatography pancreatitis

The objective of the present study was to determine the efficacy of prophylactic administration of gabexate for the prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis, hyperamylasemia and pancreatic pain. Patients scheduled for ERCP were randomized into two groups in a double-blind manner: the patients in the gabexate group were treated with continuous intravenous infusion of 300 mg gabexate dissolved in 500 mL Ringer's solution at 111 mL/h, starting 30 min before the endoscopic maneuvers and continuing up to 4 h after them; placebo group patients were treated only with Ringer's solution also starting 30 min before the endoscopic maneuvers and continuing up to 4 h. Data for 193 patients were analyzed. The incidence of post-ERCP pancreatitis was 3 patients (3.1 percent) in the gabexate group and 10 (10.5 percent) in the placebo group (P = 0.040). The incidence of hyperamylasemia was 33 patients (33.7 percent) in the gabexate group and 42 (43.7 percent) in the placebo group (P = 0.133). The incidence of pancreatic pain was 15 patients (15.3 percent) in the gabexate group and 28 (29.5 percent) in the placebo group (P = 0.018). The results suggest that a 4.5-h infusion of gabexate (for a total of 300 mg) could prevent post-ERCP pancreatitis and pancreatic pain.

Risk Factors for Post-ERCP Pancreatitis after Needle Knife Sphincterotomy following Repeated Probing / 대한소화기내시경학회지

BACKGROUND/AIMS: Needle knife sphincterotomy (NKS) following repeated probing due to difficult cannulation during ERCP increase the risk of post-ERCP pancreatitis. However, the risk factors for post-ERCP pancreatitis are not well-known. The aim of this study is to investigate the incidence and risk factors of post-ERCP pancreatitis in patients who underwent NKS. We also evaluated the effect of gabexate on the prevention of post-ERCP pancreatitis. METHODS: Medical records from a total of 200 patients who underwent NKS following repeated probing during ERCP were reviewed retrospectively. The potential risk factors for post-ERCP pancreatitis were investigated. The effect of gabexate infusion after ERCP procedure on the incidence of post-ERCP pancreatitis was also evaluated. RESULTS: A total of 13 (6.5%) patients out of 200 patients developed post-ERCP pancreatitis. Gender, age, the presence of pancreatitis at procedure, underlyng disease, direction of sphincterotomy, success or failure of cannulation, diameter of CBD, pancreatic duct status and the presence of acinar filling were proved unrelated with pancreatitis. Post-ERCP pancreatitis developed in 9 out of 38 (23.7%) when gabexate was given, while 4 out of 160 (2.5%) experienced pancreatitis without administration of gabexate. CONCLUSIONS: We couldn't determine any risk factor for pancreatitis in patients who underwent NKS following repeated probing during ERCP. The gabexate infusion after ERCP procedure might be associated with the increased risk of pancreatitis.

Effects of Gabexate Mesilate (Foy(R)) on Endotoxin-Induced Acute Lung Injury in Rabbit / 대한마취과학회지

BACKGROUND: This study was to clarify the effects of gabexate mesilate (Foy(R)), a synthetic protease inhibitor, on endotoxin induced acute lung injury in rabbit. METHODS: Animals were randomly assigned to one of four groups: saline only (n = 7), saline and Escherichia coli endotoxin 5 mg/kg over 30 mins (n = 7), Foy(R) 1 mg/kg bolus, followed by infusion of Foy(R) at 1 mg/kg/h and endotoxin (n = 7), Foy(R) 2 mg/kg bolus, followed by infusion of Foy(R) at 2 mg/kg/h and endotoxin (n = 7). Infusion of saline or Foy(R) was started 0.5 hour before the start of infusion of saline or endotoxin and continued for 6.5 hours. At the end infusion animals were sacrificed, and the wet to dry (W/D) weight ratio of lung, lung injury score and leukocyte counts, percentage of polymorphonuclear leukocyte (PMNL), and concentrations of albumin and interleukin-8 (IL-8) in bronchoalveolar lavage fluid (BALF) were evaluated. RESULTS: Endotoxin decreased the PaO2 and peripheral blood leukocyte and platelet counts. And it increased the W/D weight ratio of lung, lung injury score and leukocyte counts, percentage of PMNL, and concentrations of albumin and IL-8 in BALF. Foy(R) attenuated all these changes except the decreased peripheral blood leukocyte count. CONCLUSIONS: These findings suggest that Foy(R) attenuates endotoxin-induced acute lung injury in rabbit by inhibiting neutrophil, IL-8 and platelet responses which may play a central role in sepsis related lung injury.

The Effect of Gabexate Mesylate in vivo Model of Intimal Hyperplasia on the Activity of Matrix Metalloproteinase and Proliferation of Smooth Muscle Cell

PURPOSE: Migration and proliferation of vascular smooth muscle cells (VSMCs) are important for neointimal formation after arterial injury. Migration of VSMCs requires the degradation of basement membrane and extracellular matrix surrounding the cell. There is increasing evidence that VSMCs produce extracellular matrix-degradating proteinases, such as matrix metalloproteinases (MMPs) after arterial injury. METHOD: To assess the effect of gabexate mesylate, an MMP inhibitor, in VSMCs proliferation, migration and intimal thickening, the gelatinolytic activity of MMPs and the expression of VSMC alpha-actin mRNA were analyzed in the balloon-injured rat aorta model. Forty male Sprague-Dawley rats, weighing of 250 to 300 g, underwent aortic intimal denudation with a 2 F balloon catheter. The rats were divided into two groups: the control group (n=20: no medication), and the treatment group (n=20: daily intraperitoneal injection of gabexate mesylate (5.0 mg/kg)). The aorta was harvested at various time intervals, 1, 5, 7, and 21 days after the injury. MMP expression was analyzed by using gelatin zymography, the VSMC alpha-actin mRNA expression was analyzed by RT-PCR, and the intima to media area ratio (IMAR) were evaluated microscopically. RESULT: The treatment group showed significant suppression of intimal hyperplasia compared to the control group on day 21 (P<0.05). Mean IMAR on day 21 were 1.18+/-0.2 in the control group and 0.61+/-0.06 in the treatment group. The gelatinolytic activity of MMP-9 on day 1 after injury was significantly lower in the treatment group compared to the control group (P<0.05). The gelatinolytic activity of activated MMP-2 on days 5, 7, and 21 after injury, decreased significantly in the treatment group compared to the control group (P<0.05). The expression of VSMC alpha-actin mRNA increased on days 7 and 21 after injury. Although the expression of VSMC alpha-actin mRNA was lower in the treatment group, it was not statistically significant. CONCLUSION: These results suggest that gabexate mesylate suppresses intimal hyperplasia formation after arterial injury by decreasing activation of MMP.

The Effects of Gabexate Mesilate on the Ishemia-Reperfusion Injury in the Rabbit Liver

PURPOSE: Ischemia-reperfusion is an important pathologic process that leads to impairment of the liver after major surgery. Ischmia-reperfusion injury includes both hypoxia and an inflammatory response associated with reperfusion; the former is caused by the lack of microvascular perfusion and the latter is mediated by cytyokines and oxygen free radicals. In addition to inhibiting thrombin, plasmin, kalikrein, trypsin, and neutrophil elastase, gabexate mesilate also plays an important role in inhibiting cytokines and oxygen free radical production. The purpose of this study was to investigate the effects of gabexate mesilate on ischemia- reperfusion injury in the liver. METHODS: Twenty-four New Zealand white rabbits were divided into three groups. Clamping was not done in group A (n=8), although it was done in group B (n=8) and group C (n=8). Group C received intravenous infusion of gabexate mesilate (10 mg/kg/hr) continuously during the process of clamping. Serum alanine aminotrasferase (ALT) and purine nucleoside phophorylase (PNP) were measured immediately before clamping, following 30-minute ischemia, and after 60-minute reperfusion. Hepatic tissue adenosine triphophate (ATP), xanthine oxidase, and malondialdehyde (MDA) plus 4-hydroxyalcenals (4HA) were measured after reperfusion. RESULTS: Compared with group A, group B and group C demonstrated a significant increase in ALT and PNP levels following ischemia and reperfusion, as well as in xanthine oxidase and MDA plus 4HA levels following reperfusion. However, ATP levels showed no significant differences among the three groups. ALT levels were significantly lower in group C than in group B following reperfusion (P<0.01),although there was no significant differences in PNP levels between them. Xanthine oxidase and MDA plus 4HA levels were significantly lower in group C than in group B (P<0.05). The results suggest that gabexate mesilate inhibits an increase in ALT, xanthine oxidase, and MDA plus 4HA levels. CONCLUSION: Gabexate mesilate inhibits oxygen free radical production of xanthine oxidase, and results in a reduction of hepatic ischemia-reperfusion injury.

Effects of Gabexate Mesilate for the Prevention of Pancreatic Damage Related to ERCP / 대한소화기내시경학회지

BACKGROUND/AIMS: Recent studies reported that 1g of gabexate mesilate (GM) was effective in preventing endoscopic retrograde cholangiopancreatography (ERCP)-related pancreatic damage. The aim of this study was to evaluate the effectiveness of low dose GM for the prevention of ERCP-related pancreatic damage. METHODS: This study was performed prospectively with 102 consecutive patients (68 for the GM group, 34 for the placebo group) who were scheduled for ERCP. Infusion of GM (500 mg) was started 30 minutes before ERCP and continued for 12 hours afterward. The serum amylase and lipase were measured before ERCP and 4, 8, and 24 houps after ERCP. RESULTS: The incidence of hyperenzymemia was 45.6% in the GM group and 55.9% in the control group (p=0.40). Acute pancreatitis was developed in only one patient who was given the placebo. Although difficult cannulation, visualization of the pancreatic duct, performance of therapeutic procedures, and longer total procedure time were associated with an increased incidence of hyperenzymemia, the incidence of pancreatic damage was not affected by the GM treatment in these conditions. CONCLUSIONS: Prophylactic treatment with 500 mg of GM has no advantage for the prevention of ERCP-related pancreatic damage. Considering the cost effectiveness, further studies are necessary to identify the patients at greatest risk fot acute pancreatitis.

Gabexate for the Prevention of Pancreatic Complications Following Endoscopic Retrograde Cholangiopancreatography / 대한소화기내시경학회지

BACKGROUND/AIMS: Gabexate, a protease inhibitor, has been known to prevent pancreatic damage following ERCP. We conducted a prospective and randomized study to assess the preventive effect of gabexate. Methods: Of the 96 patients enrolled, 46 were treated with gabexate and 50 with placebo. The groups were similar with regard to sex, age, body-mass index, and the final diagnosis of ERCP. RESULTS: 24 patients (25.0%) had elevated pancreatic-enzyme levels; the frequency was similar in the two groups (P=0.48). Mean serum amylase value at 4 hours after ERCP was similar in patients with elevated basal level (220.5+/-43.2 U/L) and those with normal basal level (170.4+/-31.2 U/L). After the procedures, serum amylase values were lower in the gabexate group (137.1+/-19.8 U/L) than in the placebo group (212.0+/-50.4 U/L). The differences were not significant in the mean levels of amylase between the groups for any of imaging of the pancreatic ducts (pancreatic-duct imaging, 201.5+/-49.4 U/L, bile-duct imaging, 153.7+/-30.0 U/L). But in the patients with pancreatic duct imaging, serum amylase values were significantly higher in the placebo group (295.0+/-97.6 U/L) than in the gabexate group (112.0+/-10.6 U/L)(p<0.05). CONCLUSIONS: Prophylactic treatment with gabexate does not reduce pancreatic damage related to ERCP, but only in the patients with pancreatic duct imaging there were the significant differences between in the gabexate group and in the placebo group.

Application of Gabexate Mesylate IC against MMP - 9 Using ex vivo Model in Gastric Cancer: Prognostic Factor and Selection Criteria for Anti - MMP Treatment / 대한암학회지

PURPOSE: Among the many biological characteristics of cancer, matrix metalloproteinases(MMPs) are essential for tumor invasion and metastasis. The correction of the imbalance between MMPs and tissue inhibitors of matrix metalloproteinase (TIMP) has been suggested as a possible goal for the control of invasive phenotype of the cancer. To test the possible inhibition of MMP-9 in ex vivo model and the selection of the patients who are sensitive to MMP inhibitory (MMPI) treatment, we evaluated IC50 of the gabexate mesylate (Foy) against MMP-9 and compared them to the clinical parameters and patients survivals. MATERIALS AND METHODS: Thirty-four paired normal and gastric cancer tissues were tested for the IC50 of the gabexate mesylate. MMP-9 activity was measured by zymography. RESULTS: MMP-9 expression (percent of sample band density to control band) (p=0.04) and IC50 (p=0.02) of cancer tissues were significantly higher than those of normal tissues. Cancer tissue IC50 was higher than that of normal tissues in cases when the tumor mass diameter was longer than 5 cm (p=0.03) as well as in higher T-stage (p=0.04), lymph node metastasis (p=0.04) and in advanced stages (p=0.04). There was a tendency of increased IC50 of diffuse and mixed type than that of intestinal type (diffuse & mixed: 11.0+-20.8 mg/ml, intestinal: 2.7+-3.9 mg/ml; p 0.07), in spite of no difference in MMP-9 expression (diffuse & mixed: 40.3+49.2%, intestinal: 51.0+-58.0%). In early gastric cancer (EGC), there was no difference in IC50 between normal and cancer tissues whereas cancer tissue IC50 was higher than that of normal tissue in advanced gastric cancer (p 0.02). There was a tendency of increment of ICo in cancer tissues of advanced gastric cancer than that of EGC whereas no difference was found in MMP-9 expression between these types of cancers. Poor prognosis was found in high IC50 patients in curatively resected patients (p=0.04). In multivariate analysis, high IC50 was suggested as a possible independent prognostic factor. CONCLUSION: We could differentiate the high risk patients using IC50 of gabexate mesylate in ex vivo model. This model can be applied in detecting patients with poor prognosis and patients who can have a possible benefit with MMPI treatment.

A Study on the Effect of Combination Therapy with Anti - Thrombin III and Gabexate Mesilate in Premature Infants for Disseminated Intravascular Coagulation

PURPOSE: Both antithrombin III(ATIII) and Gabexate mesilate(Foy) are effective for the treatment of disseminated intravascular coagulation(DIC). However, their mechanisms of action are slightly different, and combined effect of ATIII and Foy in premature infant with DIC has not been studied. We evaluated therapeutic efficacy of treatments with either ATIII or Foy alone or both in combination. METHODS: We studied 23 premature infants of gestational ages between 30 and 36 weeks with DIC. Group A(n=10) was treated by ATIII only, Group B(n=7) by Foy only and Group C(n=6) by both ATIII and Foy. Three groups were compared for volume of blood sampling and transfusion and hematologic data. RESULTS: Improvement of hematologic data(platelet, PT, aPTT, fibrinogen, FDP) was not significantly different among 3 groups. The mean volume of blood sampling during 5 days of treatment was 30 mL, 22.5 mL, and 30 mL, respectively. The mean volume of packed RBC transfusion was 12.8 mL, 9 mL, and 2.5 mL, respectively: and mean volume of platelet transfusion was 25.9 mL, 10 mL, and 0 mL, respectively, showing no significant statistical difference. But the mean volume of FFP transfusion was 141 mL only in group B, significantly higher compared to other groups. CONCLUSION: The combination therapy of ATIII and Foy significantly decreased the volume of FFP transfusion and may be more effective than monotherapy with ATIII or Foy alone in DIC of premature infant.