Compression anastomotic ring-locking procedure (CARP) is a safe and effective method for intestinal anastomoses following left-sided colonic resection.

BACKGROUND: Compression anastomotic ring-locking procedure (CARP) is a novel procedure for creating colonic anastomoses. The surgical procedure allows perioperative quantification of the compression pressure between the intestinal ends within the anastomosis and postoperative monitoring of the anastomotic integrity. We have recently shown that CARP is a safe and effective method for colonic anastomoses in pigs, and the purpose of the present study was to evaluate CARP for colonic anastomoses in humans. MATERIALS AND METHODS: This is a prospective study on 25 patients undergoing elective left-sided colonic resection. Time for evacuation of the anastomotic rings, perioperative compression pressure, and adverse effects were recorded. Postoperative blood samples were collected daily, and flexible sigmoidoscopy was performed 8-12 weeks after surgery to examine the anastomoses. RESULTS: Fourteen out of 25 patients underwent CARP. CARP was not used in 11 patients due to advanced tumor disease (two cases) and size restrictions (nine cases). No case of anastomotic leakage, bowel obstruction, or stenosis formation was observed. No device-related perioperative adverse events were noted. The surgical device evacuated spontaneously in all patients by the natural route after a median of 10 days. Perioperative compression pressure ranged between 85 and 280 mBar (median 130 mBar). Flexible sigmoidoscopy revealed smooth anastomoses without signs of pathological inflammation or stenosis in all cases. CONCLUSION: Our results indicate that the novel suture-less CARP is a safe and effective method for creating colonic anastomoses. Further studies are warranted in larger patient populations to compare CARP head-on-head with stapled and/or hand-sewn colonic anastomoses.

Farnesyltransferase regulates neutrophil recruitment and tissue damage in acute pancreatitis.

OBJECTIVES: The signaling mechanisms controlling organ damage in the pancreas in severe acute pancreatitis (AP) remain elusive. Herein, we examined the role of farnesyltransferase signaling in AP. METHODS: Pancreatitis was provoked by the infusion of taurocholate into the pancreatic duct in C57BL/6 mice. Animals were treated with a farnesyltransferase inhibitor FTI-277 (25 mg/kg) before pancreatitis induction. RESULTS: FTI-277 decreased the blood amylase levels, pancreatic neutrophil infiltration, hemorrhage, and edema formation in the pancreas in mice challenged with taurocholate. Farnesyltransferase inhibition reduced the myeloperoxidase levels in the pancreas and lungs in response to taurocholate infusion. However, FTI-277 had no effect on the taurocholate-provoked formation of macrophage inflammatory protein-2 in the pancreas. Interestingly, farnesyltransferase inhibition abolished the neutrophil expression of macrophage-1 antigen in mice with pancreatitis. In addition, FTI-277 decreased the taurocholate-induced activation of the rat sarcoma protein in the pancreas. An important role of farnesyltransferase was confirmed in L-arginine-induced pancreatitis. CONCLUSIONS: These results demonstrate that farnesyltransferase signaling plays a significant role in AP by regulating neutrophil infiltration and tissue injury via the neutrophil expression of macrophage-1 antigen. Thus, our findings not only elucidate novel signaling mechanisms in pancreatitis but also suggest that farnesyltransferase might constitute a target in the management of severe AP.

A prospective cohort study on risk of acute pancreatitis related to serum triglycerides, cholesterol and fasting glucose.

BACKGROUND/OBJECTIVES: To investigate risk for acute pancreatitis related to moderately elevated triglycerides, cholesterol and fasting glucose. METHODS: This was a prospective cohort study in Malmö, Sweden of 33,346 subjects investigated 1974-1992 and followed until December 31, 2006. Baseline investigation included a self-administered questionnaire and analysis of serum triglycerides, cholesterol and fasting glucose. Cases of acute pancreatitis (n = 277, median time since baseline investigation 15.6 years) were identified in diagnosis registries and validated retrospectively. Attacks were classified as obstructive or non obstructive (alcohol or non alcohol related). Cox proportional hazards analysis was used to calculate hazard ratios (HR) for acute pancreatitis related to relevant risk factors, adjusting for age, sex, smoking habits and alcohol consumption. RESULTS: Triglycerides were associated with overall, non obstructive and non obstructive non alcohol related acute pancreatitis with adjusted HRs of 1.21 (95% confidence interval (CI), 1.07-1.36), 1.23 (95% CI, 1.06-2.43) and 1.34 (95% CI, 1.11-1.62) per 1 mmol/l increment, respectively. Corresponding HRs for forth versus first quartile of triglycerides were 1.55 (95% CI, 1.09-2.21), 1.60 (95% CI, 1.60-1.01-1.35) and 2.07 (95% CI, 1.13-3.79). Triglycerides were not associated with obstructive acute pancreatitis and there were no associations between glucose or cholesterol and the risk of acute pancreatitis. CONCLUSIONS: We found an association between prediagnostic levels of triglycerides and risk for acute pancreatitis. This association was most pronounced in the non obstructive non alcohol related group. Our findings suggest that triglycerides may be a more important risk factor for acute pancreatitis than what has previously been estimated.

A prospective cohort study of smoking in acute pancreatitis.

BACKGROUND/AIMS: Little is known about risk factors for acute pancreatitis other than gallstones and alcohol consumption. The aim of this study was to investigate if smoking or body mass index (BMI) are associated with acute pancreatitis and to determine relative risks (RR) for acute pancreatitis related to smoking, BMI, and alcohol consumption. METHODS: From 1974 to 1992, selected birth-year cohorts of residents in Malmo, Sweden (born 1921-1949) were invited to a health-screening investigation including physical examination, blood sampling and a questionnaire. In total, 33,346 individuals participated. Cases of acute pancreatitis were identified from diagnosis registries (n = 179). Incidence rates were calculated in different risk factor categories. A Cox's analysis revealed RR. RESULTS: Current versus never smoking at baseline was associated with acute pancreatitis (RR 2.14, 95% confidence interval (CI) 1.48-3.09) after adjustment for age, sex, BMI and alcohol consumption. This association was stronger in heavy smokers (20-30 cigarettes/day) (RR 3.19, 95% CI 2.03-5.00). Smoking was associated with a RR of 3.57 (95% CI 0.98-13.0) for acute pancreatitis in subjects who reported no alcohol consumption. An increased risk for acute pancreatitis was also found for high versus low risk, self-reported alcohol consumption (RR 2.55, 95% CI 1.59-4.08) and for gamma-GT levels in the highest versus the lowest quartile (RR 2.14, 95% CI 1.32-3.49). There was also a weak correlation between BMI and acute pancreatitis. CONCLUSIONS: Smoking is associated with the incidence of acute pancreatitis in a dose-response manner. and IAP.

Trends in incidence of acute pancreatitis in a Swedish population: is there really an increase?

BACKGROUND AND AIMS: Recent reports have suggested an increasing incidence of acute pancreatitis, and changing patterns of risk factors, over the past decades. The aim of this study was to investigate trends in the incidence of acute pancreatitis, and risk factors related to the disease, in a general population over a 15-year period. METHODS: Clinical, autopsy, and forensic records for all patients with a first attack of acute pancreatitis in Malmö, Sweden, from 1985 to 1999, were validated retrospectively. Evidence for diagnosis was reconsidered and plausible cause was assessed. The incidence of gallstone disease, lung cancer, and alcohol-related conditions in the background population were retrieved from hospital diagnosis records and cancer and cause-of-death registries. RESULTS: A total of 929 first attacks of acute pancreatitis were identified. The total incidence of acute pancreatitis increased by 3.9% per year (95% confidence interval [CI], 2.1-5.8). The incidence of gallstone-related pancreatitis increased by 7.6% per year (95% CI, 4.0-11.4), and this correlated with an increase in the incidence of other gallstone-related conditions ( r = 0.68; P = 0.005). Alcohol-related pancreatitis decreased by -5.1% per year (95% CI, -7.4 to -2.8), and this correlated with a decrease in the incidence of delirium tremens ( r = 0.75; P = 0.001), mortality from cirrhosis ( r = 0.81; P < 0.001), and incidence of lung cancer ( r = 0.57; P = 0.026). CONCLUSIONS: There was a statistically significant increase in the incidence of acute pancreatitis. Gallstone-related pancreatitis increased, and alcohol-related pancreatitis decreased. Both of these trends were statistically significant and correlated with trends in the incidence of other conditions associated with either gallstone disease or alcohol abuse.

A study on the activation peptide released from procarboxypeptidase B (CAPAP) and anionic trypsinogen in patients with acute abdominal disorders of non-pancreatic origin.

BACKGROUND: The activation peptide released from procarboxypeptidase B, CAPAP, is a marker of the activation of pancreatic enzymes in acute pancreatitis while anionic trypsinogen (AT) levels in urine relate to leakage of unactivated proenzymes. Data on these markers in patients suffering from severe acute abdominal disorders of non-pancreatic origin are lacking. PURPOSE: To examine levels of CAPAP and AT in serum and urine from patients with severe acute abdominal disorders of non-pancreatic origin in order to better define the diagnostic specificity of these two markers in severe acute pancreatitis in relation to other acute intra-abdominal disorders. SUBJECTS AND METHODS: The study included 54 patients with severe acute abdominal disorders of non-pancreatic origin with an APACHE II score >3. Immunoreactive CAPAP (irCAPAP) and immunoreactive AT (irAT) were measured in serum and urine using specific immunoassays. RESULTS: In urine, irCAPAP levels were mildly increased (>2 nmol/l) in 13% of the patients with severe acute abdominal diseases of non-pancreatic origin, but on no occasion did the increase approach the cutoff levels described for severe acute pancreatitis (>100 nmol/l). However, irAT levels in serum and urine were increased (>50 micro g/l) in 54% of the cases. CONCLUSION: Contrary to what is found for irAT, patients with acute abdominal pain of non-pancreatic origin rarely have markedly increased levels of irCAPAP in serum and urine.

Acute pancreatitis in Soweto, South Africa: relationship between trypsinogen load, trypsinogen activation, and fibrinolysis.

OBJECTIVE: It is not known why acute pancreatitis in Soweto, South Africa, pursues an aggressive course. We sought clues from circulating trypsinogen load at admission as marker of initial acinar injury, trypsinogen activation using the carboxypeptidase B activation peptide as surrogate, proteinase inhibitors, the coagulation-fibrinolysis axis, indicators of inflammation, oxidative stress markers, and antioxidant status. This article reports on the first four aspects. METHODS: The study involved 24 consecutive patients with a first attack. All of them were admitted within 24 h, and 22 were alcoholic. Urine was analyzed for anionic trypsinogen and the carboxypeptidase B activation peptide. Serum was tested for anionic and cationic trypsinogen, alpha1 proteinase inhibitor and alpha2 macroglobulin. Plasma from a subset was assayed for soluble fibrin, cross-linked fibrin degradation products (surrogates for thrombin and plasmin activity, respectively), and tissue-type plasminogen activator and inhibitor. RESULTS: Soweto controls had higher serum anionic trypsinogen (p = 0.004) and plasminogen activator:inhibitor ratio (p = 0.047) than U.K. controls. The outcome of acute pancreatitis was mild in 17 but severe in seven with three deaths, two on day 2. In mild pancreatitis, intense plasmin activity (p < 0.001) accompanied the surge in trypsinogen, especially anionic (p < 0.001), but without increased thrombin activity and in five patients without trypsinogen activation. In severe pancreatitis, further significant increments in plasmin activity and trypsinogens were accompanied by increased thrombin activity (p = 0.013) and trypsinogen activation (p = 0.046). There was no correlation between surrogates of plasmin and thrombin activity, or between either and the carboxypeptidase B activation peptide, which showed a curvilinear relationship to total serum trypsinogen. CONCLUSIONS: The aggressive nature of alcoholic acute pancreatitis in Soweto seems to reflect early profound fibrinolysis, which precedes coagulation and is initially independent of trypsin. Subclinical acinar-cell injury and a profibrinolytic diathesis in outwardly healthy Sowetans may predispose to this problem.