Efficacy of Recombinant Human-Soluble Thrombomodulin for Severe Acute Pancreatitis in a Rat Experimental Model.

OBJECTIVES: Early death in severe acute pancreatitis (SAP) is caused by pancreatic necrosis and multiple-organ failure due to microcirculation disorder. The aim of this study was to prove that recombinant human-soluble thrombomodulin (rTM) has therapeutic effects on SAP by preventing pancreatic necrosis and organ failure. METHODS: Male Wister rats were used. Cerulein was administered intraperitoneally 4 times every 1 hour, and lipopolysaccharide was administered intraperitoneally 3 hours after. One hour after administration of lipopolysaccharide, rTM was injected intravenously. Rats were observed for 24 hours after starting the experiment, and the survival rate was evaluated. All surviving rats were killed, and the blood sample, liver, and pancreas were excised. Serum amylase, aspartate aminotransferase, alanine aminotransferase, and high mobility group box 1 were measured, and the liver and pancreas were examined histologically. For the evaluation of microcirculation, von Willebrand factor staining was performed. RESULTS: Serum amylase, aspartate aminotransferase, and alanine aminotransferase were significantly decreased. The survival rate was significantly improved to 100%. Moreover, serum high mobility group box 1 was decreased. Liver injury and pancreatic necrosis became less severe, and microcirculation was preserved histologically. CONCLUSIONS: Early administration of rTM prevents organ failure by maintenance of microcirculation and improves prognoses of SAP.

Pancreas lipiodol embolism induced acute necrotizing pancreatitis following transcatheter arterial chemoembolization for hepatocellular carcinoma: A case report and literature review.

RATIONALE: Transcatheter arterial chemoembolization (TACE) is recognized as one of the most commonly used modalities for non-surgical treatment for advanced hepatocellular carcinoma (HCC). Ectopic lipiodol embolism is an extremely rare complication of TACE. PATIENT CONCERNS: A 61-year-old man who had a 10-year history of cirrhosis caused by hepatitis B infection was diagnosed with ascites and HCC. Subsequently, the patient underwent TACE. However, he experienced persistent left upper abdominal pain, poor appetite, nausea, moderate fever and accompanied by elevation of serum and urine amylase on the 2nd and 3nd day after treatment. DIAGNOSES: The patient was diagnosed as having acute hemorrhagic necrotizing pancreatitis based on biochemical and inflammatory markers and CT findings. We deduced that the acute necrotizing pancreatitis was caused by a small branch of the left hepatic artery feeding the pancreas tail and embolizing the drug and lipiodol shunting to the tail of the pancreas. INTERVENTIONS: The patient was treated for 5 days according to the comprehensive treatment of acute necrotizing pancreatitis, by the inhibition of the secretion of pancreatic juice, relieving pain, and total parenteral nutrition and forbidding diet. The symptoms of the patient were observed to improve, and SAMS and urinary amylase (UAMS) level decreased to 143 IU/L and 254 IU/L, respectively and oral diet was permitted. OUTCOME: After a period of 2 weeks, the contrast abdominal CT showed slightly decreased fluid collection of the peri-pancreatic space. Moreover, it also showed flocculous and linear high-density shadow in the pancreatic tail, suggesting lipiodol deposition in the pancreatic tail. Subsequently, the symptoms were observed to abate, and the patient left the hospital. On the 21st day after TACE, the patient had a follow up in our outpatient department; the biochemical characteristics and inflammatory markers were observed to be normal CONCLUSION:: AP is still a rare complication after TACE. Etiology is still attributed to the occurrence of shunting and embolization drug reflux. Strategies strengthening the catheter tip that is placed as close to the distal branches of the hepatic artery for the possible careful injection of embolic materials is still the key to avoid post-TACE AP.

Effects of Berberine on Acute Necrotizing Pancreatitis and Associated Lung Injury.

OBJECTIVES: We set out to examine whether berberine (BBR) might affect the severity of pancreatitis and pancreatitis-associated lung injury in choline-deficient ethionine-supplemented (CDE) diet-induced severe acute pancreatitis. METHODS: Severe acute pancreatitis was induced by feeding a CDE diet for 3 days. Berberine was administered intraperitoneally during CDE diet. Mice were killed on days 1, 2, and 3 after the onset of CDE diet. The severity of pancreatitis was assessed by evaluating changes to the pancreas and lung and survival rate. Blood, pancreas, and lung were harvested for further examination. Furthermore, the regulating mechanisms of BBR were evaluated on the pancreas. RESULTS: Administration of BBR significantly inhibited histological damage to the pancreas and lung and decreased serum level of amylase and lipase, myeloperoxidase activity, cytokine production, and the mortality rate. Furthermore, administration of BBR inhibited activation of nuclear factor kappa B, c-Jun N-terminal kinases, and p38 in the pancreas during CDE diet. CONCLUSIONS: These findings suggest that BBR attenuates the severity of pancreatitis by inhibiting activation of nuclear factor kappa B, c-Jun N-terminal kinase, and p38 and that BBR could be used as a beneficial agent to regulate AP.

Akute Pankreatitis nach nicht chirurgischer Parodontaltherapie in Kombination mit systemischer Antibiotikatherapie.

Non-surgical periodontal therapy is often performed as a combinational approach using supplemental systemic amoxicillin and metronidazole. Better clinical outcomes, less need for periodontal surgery and limited systemic complications are arguments to justify such an approach. However, combination therapy with systemic antibiotic treatment is still a matter of debate due to emerging antibiotic resistance patterns. In this case report, a 61-year-old women suffering from an acute pancreatitis following systemic antibiotic combinational treatment as part of a non-surgical periodontal therapy is described. Following adequate symptomatic treatment during a hospitalization of three days, the patient recovered and periodontal conditions improved significantly thereafter. This case report illustrates a rare, but potentially serious complication when prescribing systemic combinational antibiotics in non-surgical periodontal therapy. Adequate history taking and timely diagnosis of pancreatitis if developing is important to provide relevant treatment and to avoid pancreatitis-associated complications.

Catalpol ameliorates sodium taurocholate-induced acute pancreatitis in rats via inhibiting activation of nuclear factor kappa B.

Catalpol, an iridoid glucoside extracted from the traditional Chinese herbal medicine, Rehmannia glutinosa, is reported to exert neuroprotective, anti-inflammatory, anti-tumor and anti-apoptotic effects. The main aim of the present study was to investigate whether catalpol ameliorates experimental acute pancreatitis (AP) induced by sodium taurocholate (STC). AP was induced in rats via retrograde injection of 4% STC (0.1 mL/100 g) into the biliopancreatic duct. Rats were pre-treated with saline or catalpol (50 mg/kg) 2 h before STC injection. At 12, 24 and 48 h after injection, the severity of AP was evaluated using biochemical and morphological analyses. Pretreatment with catalpol led to a significant reduction in serum amylase and lipase activities, pancreatic histological damage, myeloperoxidase (MPO) activity, interleukin (IL)-1ß, IL-6 and TNF-α levels, and activation of nuclear factor kappa B (NF-κB). Moreover, administration of catalpol increased the viability of pancreatic acinar cells and inhibited NF-κB expression in vitro. Our results collectively support the potential of catalpol as a highly effective therapeutic agent for treatment of AP.

[Nutritional support and efficient gastroduodenal endoscopy in the treatment of acute pancreatitis and different forms of pancreonecrosis].

Nutrition support and molecular-genetic markers of the immune system at patients with complicated forms of gastric pathology. In this study presented results of surgery clinic of and oncology faculty SGMU to improve treatment patients with acute pancreatitis, and various forms of pancreonecrozis, through a balanced Threpsology support and operational gastrointestinal endoscopy.

[Clinical study of Yihuo Qingxia method in treating hyperlipoidemia-related severe acute pancreatitis in early stage].

OBJECTIVE: To investigate the therapeutic effect of Yihuo Qingxia method, a traditional Chinese medicine therapeutic method for replenishing qi to activate blood, clearing away heat and dredging intestines, in treating hyperlipoidemia-related severe acute pancreatitis (SAP) in early stage. METHODS: One hundred and four patients with hyperlipoidemia-related SAP were divided into two groups: early group (admitted to hospital within 3 days after onset) and late group (admitted to hospital from 3 days to 7 days after onset). There were 52 cases in each group. All the patients were treated by Yihuo Qingxia method. RESULTS: There were no statistical differences in 48-hour Ranson scores, CT scores, 24-hour acute physiology and chronic heath evaluation II scores (APACHE II scores), and the levels of 24-hour serum triglyceride (TG) and serum glucose in the two groups (P>0.05). At the 10th day after onset, the serum TG level in early group was lower than that in late group (P<0.01). The incidences of acute respiratory distress syndrome, acute renal failure, hepatic inadequacy, congestive heart failure, shock, encephalopathy, infection and alimentary tract hemorrhage in early group were higher than those in late group (P<0.05). The mortality in early group was lower than that in the late group (P<0.05). The length of hospital stay in early group was shorter than that in late group (P<0.05). CONCLUSION: Yihuo Qingxia method has a good efficacy in treating hyperlipoidemia-related SAP in early stage.

[Clinical study on 100 cases of severe acute pancreatitis in aged patients].

OBJECTIVE: To analyze the clinical features of severe acute pancreatitis (SAP) in aged patients, and to explore the measures of its diagnosis and treatment. METHODS: The clinical data of 100 aged patients (55-85 years old) with SAP admitted from January 2003 to December 2005 were reviewed and compared with those of 221 non-aged SAP patients (11-54 years old) admitted at the same period. RESULTS: Totally 112 times of onset occurred in 100 aged patients, and the main causes for senile SAP were biliary diseases and hyperlipemia. Both acute physiology and chronic health evaluation II (APACHE II) and Ranson scores of the aged patients with SAP were higher than those of the control group (P<0.05); while there was no significant difference in Balthazar score between the two groups(P>0.05). The incidences of low serum calcium, low albumin and high aspartate aminotransferase (P<0.05), liver, kidney or brain impairment as well as the mortality were higher in the senile SAP group than those in the control group (P<0.05). CONCLUSIONS: Biliary disease and hyperlipemia are the main causes of senile SAP, which lacks characteristic clinical symptoms and is often associated with multiple complications such as infection and lung, gastrointestinal tract, liver, kidney, and brain impairment. Individualized differential treatment with integrated traditional Chinese and Western medicine based on stage classification is an effective approach.

Pulmonary protective effects of hyberbaric oxygen and N-acetylcysteine treatment in necrotizing pancreatitis.

The purpose of this study is to analyze the protective effect of combining N-acetylcysteine (NAC) and hyberbaric oxygen (HBO) treatment in the lung tissue during acute pancreatitis. Sixty Sprague-Dawley male rats were randomly divided into five groups; Group I; Control group (n=12), Group II; pancreatitis group (n=12), Group III; pancreatitis + NAC treatment group (n=12), Group IV; pancreatitis + HBO treatment group (n=12), Group V; pancreatitis + HBO + NAC treatment group (n=12). HBO was applied postoperatively for 5 days, twice a day at 2.5 fold absolute atmospheric pressure for 90 min. Lung tissue was obtained for measuring malondialdehyde (MDA), superoxide dismutase (Cu/Zn-SOD) and glutathione peroxidase (GSH-Px) levels along with histopathological tissue examinations. This study showed that all three treated groups (HBO alone, NAC alone and combined HBO+NAC treatment) had pulmonary protective effects during acute necrotizing pancreatitis.

[Differential diagnosis and therapy of acute pancreatitis]. / Differentialdiagnose und Therapie der akuten Pankreatitis.

Acute pancreatitis is classified in an interstitial edematous pancreatitis and a hemorrhagic necrotizing pancreatitis comprising 80% and 20% respectively of all cases. 80% of acute pancreatitis are attributed to biliary and alcoholic origin whereas in more than 10% no etiology can be established comprising the idiopathic forms of acute pancreatitis. Clinical symptoms are rather unspecific resulting in a large number of abdominal and extraabdominal diseases that have to be considered regarding the differential diagnosis. Diagnosis is based on clinical examination, laboratory findings and ultrasound. However it has to be taken into account that a lack of abdominal symptoms and unaltered amylase and lipase levels may be present in spite of overt pancreatitis. As severe pancreatitis is associated with a steep increase in mortality the early identification of severe pancreatitis is crucial. Several prognostic scores like the Ranson-, Glasgow- and APACHE-II score were developed to achieve a higher sensitivity detecting transition to severe pancreatitis. In addition new prognostic serum parameters are applicable. A prophylactic antibiotic therapy is recommended in patients with sterile necrosis whereas an infected necrosis requires organ preserving necrosectomy and retroperitoneal lavage which can be done surgically or referring to new concepts endoscopically. Apart from renal and respiratory failure, necrosis, pseudocysts and pancreatic abscess are the main complications. In the presence of detected stones in the common bile tract ERCP in combination with stone extraction and papillotomy reduces morbidity and mortality in patients with biliary pancreatitis. Laparoscopic cholecystectomy should be performed as soon as the patient has recovered and preferably during the same hospital admission.

Guidelines for treatment of severe acute pancreatitis.

Severe acute pancreatitis is a disease of rapid onset and progression with high mortality and morbidity. A new concept suggests that it is multifactorially induced and involves multi-links and that therapy must be directed to several more important links at the same time. The regimen of integrated traditional Chinese and western medicine acts on the same or different sites and links to inhibit or block the inflammatory cascades. Concomitantly, preventive measures were taken at the start of the treatment for preventing the progression of the disease, protecting the function of vital organs, and avoiding the occurrence of complications. No mortality or serious complications occurred in a series of 38 patients with Balthazar's CT grading of D and E. The treatment regimen and the mechanisms of actions of these drugs were delineated in detail in the tables and figure; the regimen is highly recommended for clinical use.

Incidence, spectrum and antibiotic sensitivity pattern of bacterial infections among patients with acute pancreatitis.

BACKGROUND AND AIM: Secondary infection of pancreatic necrotic tissue and peripancreatic fluid is a serious complication of acute pancreatitis resulting in significant morbidity and mortality. The aim of this study was to find out the spectrum of bacterial infections, and their antibiotic sensitivity pattern in patients with acute pancreatitis. METHODS: All consecutive patients with acute pancreatitis were studied prospectively. Detailed investigations were carried out to identify bacterial infections and their antibiotic sensitivities in patients with suspected infection. These investigations included cultures of various body fluids, throat swabs, indwelling cannula and catheter tips. Pancreatic tissue was obtained by using needle aspiration or at surgery for Gram's stain, culture and sensitivity. All cultures were repeated until the presence of infection was confirmed or excluded. RESULTS: A total of 169 patients with acute pancreatitis were studied during the period between January 1997 and June 2000 (mean age 41.3 years; 116 males and 53 females). Of the 169 patients, 63 had infections at various sites. A total of 80 cultures were positive, and 12 different bacterial isolates were cultured from samples taken from these 63 patients. Polymicrobial infection was seen in 32% of patients. Twenty-four patients had a confirmed pancreatic infection. Blood cultures had a growth of organisms in 19 patients, with evidence of ongoing or worsening pancreatitis, thus raising a strong suspicion of infected necrosis in them. The commonest organisms were Escherichia coli from 20 cultures and Pseudomonas aeruginosa from 18 cultures. The antibiotic sensitivity pattern showed that most bacteria were sensitive to third generation cephalosporins and quinolones; notably among them were cefotaxime, ceftazidime, and ciprofloxacin. CONCLUSION: Bacterial infections were seen in 37% of patients with acute pancreatitis. The commonest organisms were Pseudomonas aeruginosa and Escherichia coli. Most bacterial isolates were sensitive to third generation cephalosporins and quinolones.

[Effects of calcium overload in the conversion of acute edematous pancreatitis to necrotizing pancreatitis in rats].

OBJECTIVE: To investigate the potential of pancreatic acinar cell calcium overload in the conversion of acute edematous pancreatitis (AEP) to necrotizing pancreatitis (ANP). METHODS: Ninety-six Sprague-Dawley rats were randomized in three experimental groups. Sham-operated control (Group I) AEP (Group II) was induced by pancreatic duct ligation and intravenous injection of bombesin (100 micrograms/kg) and secretin (10 micrograms/kg). ANP (Group III) was induced same as group II but with a large dose of dextran 110,000(500 mg/kg) intravenously. Pancreatic acinar cell Ca2+ overload was studied using fluorescent probe Fura2. Cytosolic free Ca2+ concentration ([Ca2+]i) in isolated pancreatic acinar cells and Ca(2+)-ATPase activity in pancreatic cell plasma membranes were determined 1, 3, 6, 9 h respectively after treatment. RESULTS: The results showed that pancreatic acinar cell [Ca2+]i was elevated at 1 h[(213 +/- 19) nmol/L, P < 0.05] and increased to (464 +/- 29) nmol/L at 6 h(P < 0.05) in rats with ANP, pancreatic cell plasma membrane Ca(2+)-ATPase activity decreased significantly from (29.8 +/- 0.4) nmol.min-1.mgp-1 at 1 h to (18.6 +/- 0.5) nmol.min-1.mgp-1 at 9 h in rats with ANP (P < 0.05). CONCLUSIONS: In ischemia-induced conversion of AEP to ANP, there exists Ca2+ overload in the pancreatic acinar cells. The decreased pancreatic cell plasma membrane Ca(2+)-ATPase activity may be an important reason for acinar cell Ca2+ overload in the development of acute pancreatitis.