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H G Beger

Publications and source records attributed to H G Beger.

At least 37 records · Page 2Linked to original sources

Diverticular disease-associated hemorrhage in the elderly.

Lower gastrointestinal bleeding is frequent in the elderly secondary to diverticular disease and occurs in about 10-30%. It is the most frequent cause of lower gastrointestinal hemorrhage (about 40% of cases) followed by angiodysplasia (up to 20% of cases). The incidence of both diseases increase with age, but the patient's general condition and state of health decrease. Often cardiovascular morbidity coexists, resulting in an eventual risk of ischemic consequences. The intensity of bleeding varies from massive to occult. In diverticular disease, hemorrhage is caused by rupture or erosion of the vasa recti stretched by diverticula. Classically inflammation is absent. Although most diverticula (> 90%) are located in the sigmoid colon, bleeding originates more frequently from the right (> 50%) than the left colon. The preferred diagnostic tool following resuscitation is colonoscopy with an ability to locate the site of bleeding in up to 90% of cases. Additionally, injections and thermocoagulation are available to control bleeding endoscopically with a success rate of about 27%. Angiography is considerably variable concerning positive results (13.6-86%), has a complication rate of about 10% and is expensive. Hence, it is a second-line diagnostic method. Diverticular hemorrhage will cease spontaneously in about 90% of cases. Therefore, conservative treatment is preferred. Patients with persistent, massive or recurrent bleeding despite active conservative measures require surgical treatment. If surgical intervention is necessary, the site of hemorrhage must be sought to allow segmental resection. However, if the source of blood loss cannot be located, a subtotal colectomy is justified.

Age Factors↗

Prevention of severe change in acute pancreatitis: prediction and prevention.

Bacterial infection of pancreatic necrosis is the most frequent local complication of severe acute pancreatitis and is responsible for the majority of deaths in this disease. The development of systemic complications of severe acute pancreatitis such as septic multiple organ failure is closely related to infected necrosis. In this review, the factors predisposing to a severe course of acute pancreatitis are discussed as are clinical and laboratory markers which allow identification of patients at risk. Prevention of complications of acute pancreatitis is difficult. A variety of drugs including antiproteases and antiinflammatory agents have been shown to be of no benefit with regard to the reduction of severe complications. At present, based on the results of controlled trials, there is the widespread belief that prophylactic antibiotics are capable of reducing the incidence of infected pancreatic necrosis. New approaches for the prevention of systemic complications of severe acute pancreatitis are total enteral nutrition and local arterial infusion of antibiotics and antiproteases into the celiac trunk.

Abscess↗

Neoadjuvant, adjuvant, and palliative treatment of pancreatic cancer.

Pancreatic cancer remains a highly malignant disease. Curative treatment is only possible for patients diagnosed at a very early stage. Therefore, the vast majority of pancreatic cancer patients receive palliative treatment. Surgical palliation is offered to patients who are found not to have a resectable tumor. The treatment of obstructive jaundice is managed by stenting of the common bile duct or by a surgical bypass. The best possible surgical procedure should be based on the factors that influence hospital mortality, length of survival, and quality of life. In patients with a life expectancy of longer than 3 months, surgical bypass is recommended, with hepaticojejunostomy the treatment of choice. In the same surgical procedure, the relief of duodenal obstruction with a gastroenteric bypass should be achieved. Chemotherapy, radiotherapy, or a combination of both is employed as a neoadjuvant measure, as an adjuvant treatment, or, in most patients, as palliation. As palliative chemotherapy alone, 5-fluorouracil (5-FU) plus folinic acid is still the treatment of choice; however, newer drugs, such as gemcitabine, seem to have similar or marginally better results. Palliative radiochemotherapy with external-beam radiation plus 5-FU and folinic acid seems to lead to better local control of tumor progression but not to better survival, for which distant metastases are the limiting factor.

Chemotherapy, Adjuvant↗

Pharmacokinetic basis for oral perioperative prophylaxis with ofloxacin in general surgery.

BACKGROUND: Perioperative prophylaxis is recommended to be administered intravenously which, compared to oral prophylaxis, is more expensive. However, pharmacokinetic data on oral perioperative prophylaxis in patients with preoperative surgical and anesthesiological preparation are not available. PATIENTS AND METHODS: 40 patients with open hernial repair or cholecystectomy (low-risk group), colonic or pancreatic resection (high-risk group) received a standard single-dose perioperative prophylaxis with 4.5 g mezlocillin and 0.5 g metronidazole intravenously in addition to 400 mg ofloxacin orally 2 h prior to surgery. Antibiotic concentrations were measured perioperatively and pharmacokinetic data calculated. RESULTS: Serum and tissue concentrations of ofloxacin were above the MIC90 of the potential bacterial spectrum for surgical infection throughout the entire operation. Pharmacokinetic data were not influenced by preoperative surgical or anesthesiological preparation. CONCLUSION: Tissue and serum concentrations and the antibacterial spectrum of orally administered ofloxacin suggest effective protection against perioperative infection. Pharmacokinetic data confirm that oral ofloxacin may be used effectively as single-dose perioperative antibiotic prophylaxis. Since there are no clinical data comparing oral and intravenous singLe-dose prophylaxis, a prospective randomized clinical trial should be performed.

Administration, Oral↗

Endotoxemia and acute-phase proteins in major abdominal surgery.

BACKGROUND: Translocation of endotoxin is a controversial issue. The ability of plasma to inactivate endotoxin is an indirect measure of endotoxemia. Endotoxin is a potent stimulator of the inflammatory response and affects the innate immune system. OBJECTIVE: To elucidate the kinetics of endotoxemia and the ability of plasma to inactivate endotoxin in patients with major abdominal operations. To demonstrate the early time course of the acute-phase proteins C-reactive protein (CRP), serum amyloid A (SAA), alpha(1)-antitrypsin, alpha(2)-macroglobulin, transferrin, and interleukin 6 (IL-6), and to correlate them with the amount of endotoxemia. METHODS: Twenty patients with elective major abdominal operation and 10 healthy controls were investigated. Blood was collected preoperatively, during the operation and regularly up to 12 days after surgery. Endotoxin was measured by Limulus amebocyte lysate test (LAL), the ability of plasma to inactivate endotoxin by modified LAL, the acute-phase proteins nephelometrically, and IL-6 by enzyme-linked immunosorbent assay (ELISA). RESULTS: Preoperative endotoxin plasma level (0.026 +/- 0.004 EU/mL) did not differ from healthy volunteers but increased during operation (0.09 +/- 0.02 EU/mL, P = 0.02). Endotoxemia peaked 1 hour after the surgical procedure (0.16 +/- 0.03 EU/mL; P <0.0001 versus preoperative) and decreased to almost normal values after 48 hours. The capability of plasma to inactivate endotoxin was significantly reduced during (recovery, 0.16 +/- 0.03 EU/mL), 1 hour (0.25 +/- 0.04 EU/mL) and 24 hours (0.16 +/- 0.02 EU/mL) after the operation compared with preoperative (0.068 +/- 0.01 EU/mL) values. Plasma IL-6 was significantly increased for 48 hours with a peak 1 hour after surgery (470 +/- 108 pg/mL). CRP peaked at 210 +/- 19 mg/L (P <0.0001 versus preoperative) 48 hours after operation and was significantly elevated for the rest of the observation period. SAA was significantly increased 24 hours after surgery (249 +/- 45 mg/L) and peaked additional 48 hours later (456 +/- 86 mg/L). alpha(1)-Antitrypsin, although a positive acute-phase protein, decreased initially to 1.38 +/- 0.1 g/L (preoperative, 2.33 +/- 0.18 g/L; P <0.0001) and increased thereafter until day 12 (3.05 +/- 0.35 g/L, P = 0.11 versus preoperative). The same was true for alpha(2)-macroglobulin (preoperative, 2.2 +/- 0.16 g/L; intraoperative, 1.36 +/- 0.13 g/L; day 5, 2.8 +/- 0.4 g/L). Transferrin decreased already during surgery (1.6 +/- 0.1 g/L versus preoperative 2.8 +/- 0.17 g/L, P <0.0001) and remained on this level for 5 days. Correlation analysis revealed a relationship between endotoxemia and the ability of plasma to inactivate endotoxin (r = 0.67, P <0.0001) and also a relation between intraoperative endotoxemia on one hand and alpha(2)-macroglobulin (-0.53 > r > -0.6, P <0.05) as well as alpha(1)-antitrypsin (0.64 > r >0.55, P <0.05) on the other. CONCLUSION: Major abdominal surgery is associated with transient endotoxemia and a transient reduced endotoxin inactivation capacity of the plasma. Endotoxemia correlates with the endotoxin inactivation capacity. The surgical procedure causes substantial changes in plasma concentrations of acute-phase proteins. alpha(2)-Macroglobulin and alpha(1)-antitrypsin correlate moderately with endotoxemia.

Abdomen↗

Is a preoperative multidiagnostic approach to predict surgical resectability of periampullary tumors still effective?

BACKGROUND: Multimodality staging is recommended in patients with periampullary tumors to optimize preoperative determination of resectability. We investigated the potency of currently used diagnostic procedures in order to determine resectability. METHODS: Ninety-five consecutive patients with periampullary tumors prehospitally staged resectable underwent preoperative diagnostic tests: helical-computed tomography (CT) with maximum intensity projection of arterial vessels (MIP), magnetic resonance imaging (MRI), magnetic resonance cholangiopancreaticography (MRCP), endoscopic ultrasonography (EUS), endoscopic retrograde cholangiopancreaticography (ERCP), digital subtraction angiography (DSA), and positron emission tomography (PET). Diagnoses were verified by surgery and histopathology. RESULTS: In 45 patients with benign and 50 patients with malignant periampullary tumors sensitivity for tumor diagnosis was 89% to 96% in CT, MRI, EUS, and PET. Small tumors were best diagnosed by EUS (100%). Diagnosis of malignancy was made with 85% (EUS), 83% (CT), 82% (PET), and 72% (MRI) accuracy. Arterial vessel infiltration was best predicted by CT/MIP with an accuracy of 85%. For venous vessel infiltration MRI reached 85% accuracy. Accuracy rates for local nonresectability were 93% (EUS), 92% (MRI), and 90% (CT). Two and 4 of 8 patients with distant metastases were identified by CT and PET, respectively. The correct diagnosis of malignancy and determination of resectability was made by CT in 71% and by MRI in 70%. Biliary stenting reduced accuracy of CT diagnosis of malignancy from 88% to 73%. CONCLUSIONS: CT obtained before stenting was the single most useful test, providing correct diagnosis in 88% and resectability in 71% of patients. If no tumor is depicted in CT, EUS should be added. Uncertain venous vessel infiltration can be verified by MRI or EUS. Angiography should no longer be a routine diagnostic procedure. Equivocal tumors or possible metastasis may be further examined with PET.

Ampulla of Vater↗

Surgery, radio- and chemotherapy for multimodal treatment of rectal cancer.

The possibilities and results of multimodal treatment in rectal cancer were reviewed with respect to the results of surgical treatment only. Based on the results of 4 studies, reducing local relapse rates and increasing long term survival rates significantly, postoperative radiochemotherapy (RCT) + chemotherapy (CT) should remain the recommended standard for R0 resected UICC II and III rectal cancers. The addition of RT to adjuvant CT reduces local relapses without significant impact on survival (NSABP R-02). Vice versa, the addition of CT to RT or an improved CT in the RCT-concept prolongs survival. Preoperative neoadjuvant radiotherapy (RT) reduced local relapse rates in 9 studies, and extended survival in one study that evaluated all eligible patients. Preoperative RT reduced local relapse rates in addition to total mesorectal excision (TME) but did not extend survival. The preoperative RCT + CT downstages resectable and nonresectable tumors and induces a higher sphincter preservation rate. Phase III data justifying its routine use in all UICC II + III stages are not yet available. This treatment may be routinely applied in nonresectable primary tumors or local relapses. Preoperative RCT (or RT) may evolve as standard, if the patient selection is improved and postoperative morbidity and long term toxicity reduced. Intraoperative RT could be added to this concept or be used together with preoperative/postoperative RT at the same indications. Postoperative adjuvant RT reduced local relapses significantly in a single trial, and no impact on survival time is reported. Since postoperative RT is inferior to preoperative RT, this treatment cannot be recommended, if RT is chosen as a single treatment modality in adjunction to surgery. The results of local tumor excisions may be improved with pre- or postoperative RCT + CT. In the future, multimodal treatment of rectal cancer might be more effective, if individualized according to prognostic factors.

Chemotherapy, Adjuvant↗

Differential effects of caspase-1/interleukin-1beta-converting enzyme on acinar cell necrosis and apoptosis in severe acute experimental pancreatitis.

There is recent experimental evidence that inhibition of caspase-1/interleukin-1beta converting enzyme (ICE) significantly ameliorates overall severity and survival in severe acute experimental pancreatitis. However, little is known about the effects of this approach on the dynamics and mechanisms of local acinar cell damage, which we aimed to investigate in the present study. Severe acute pancreatitis (SAP) was induced by retrograde infusion of 4% sodium taurocholate in rats treated with isotonic saline or a highly selective, irreversible inhibitor of ICE. After 3, 6, and 24 hours, 3 and 7 days, acinar cell death by necrosis and apoptosis, as well as intrapancreatic and systemic interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) expression, was assessed. Treatment with the ICE inhibitor significantly reduced the extent of acinar cell necrosis accounting for major parenchymal destruction. In contrast, apoptosis was confined to the postacute course of the disease and was closely related to tubular complex formation, both remaining unchanged. Whereas intrapancreatic IL-1beta mRNA expression was highly up-regulated in both treated and untreated animals, active IL-1beta protein expression and subsequent neutrophil tissue infiltration was dramatically decreased in the ICE-inhibited group. Parallel to the onset of enhanced apoptotic acinar cell death and tubular complex formation, TNF-alpha mRNA and protein expression was up-regulated, with levels being lower in ICE inhibitor-treated rats. We conclude that activation of caspase-1/ICE plays a central role in the progression of acinar cell death by necrosis in SAP. Herein, IL-1beta-mediated neutrophil infiltration seems to be a crucial step in enhanced cellular destruction. In contrast, acinar cell apoptosis contributes to ductal transformation and is independent of this mechanism, but may be influenced by TNF-alpha.

Acute Disease↗

Contribution of nitric oxide to the protective effects of ischemic preconditioning in ischemia-reperfused rat kidneys.

We examined the contribution of nitric oxide (NO) to the effect of ischemic preconditioning (IP) on renal function and the hemodynamics in ischemia-reperfusion (I/R) mediated kidney injury. IP was performed by using 4 minutes of ischemia followed by a 30-minute reperfusion interval. I/R treatment consisted of a 30-minute ischemia and 60-minute reperfusion interval. We measured the glomerular filtration rate (GFR), the fractional excretion of sodium (FE(Na)), and the renal blood flow (RBF) in IP+I/R and I/R kidneys. Rats were pretreated with NaCl, N(G)-nitro-L-arginine methyl ester (L-NAME), or L-arginine. We found that IP significantly improved GFR and FE(Na) as compared with I/R treatment; however, this effect was completely abolished by L-NAME injection and enhanced by L-arginine treatment. L-NAME treatment significantly diminished RBF but did not alter nitrite/nitrate excretion. Furthermore, we found that IP alone does not lead to inducible NO synthase protein expression whereas I/R or IP+I/R treatment clearly did. Moreover, we observed an increased heme oxygenase-1 expression in IP+I/R kidneys as compared with I/R treated ones. Our results clearly showed that IP pretreatment protects kidneys from I/R mediated tissue injury and that these effects were partially mediated by NO.

Animals↗

Common bile duct stenosis in complicated chronic pancreatitis.

BACKGROUND: Common bile duct stenosis (CBDS) is one of the most frequent and serious complications in patients with chronic pancreatitis. Due to improved diagnostic tools, the frequency of CBDS seems to occur more frequently, nevertheless the prevalence varies widely because of different selection criteria. METHODS: Between April 1982 and October 1996, 323 patients with chronic pancreatitis and inflammatory mass in the head of the pancreas (IMH) (286 patients) or CBDS alone (37 patients) were operated. Patients' data including US, CT, ERCP, endocrine and exocrine function tests were documented prospectively. Dividing patients into groups with and without CBDS, clinical data were comparable concerning distribution of sex, age, etiology of the disease and clinical feature. RESULTS: Regarding the subgroup of 286 patients with inflammatory mass in the head of the pancreas (IMH), 154 patients (51%) showed radiological proved CBDS; out of this group, 82 patients (57%) revealed cholestasis and 37 patients (26%) had one or several periods of jaundice. By means of ERCP, 104 patients (72%) revealed short stenosis of the common bile duct (CBD) (<2 cm). No significant differences could be found in terms of morphologic alterations like pancreatic main duct stenosis, pseudocysts, duodenum stenosis, vascular obstruction. Ten patients (7%) in the group with CBDS and 13 patients (9%) in the group without CBDS had cancer in the pancreatic head. Concerning the endocrine function, the group of patients with CBDS had a significantly elevated rate of impaired glucose metabolism (IGT or IDDM) compared to the group without CBDS (60% versus 38%; P < 0.003). These results demonstrate that patients with IMH bear the risk of developing a stenosis of the CBD even before they become symptomatic with cholestasis or jaundice. CONCLUSION: Due to the elevated morbidity and the significantly deteriorated endocrine function, patients of this group are candidates for early surgical treatment.

Adolescent↗

Modulation of endogenous nitric oxide synthase in experimental acute pancreatitis: role of anti-ICAM-1 and oxygen free radical scavengers.

OBJECTIVE: To evaluate, in an experimental model of acute pancreatitis, the impact of nitric oxide on the disease process and the interaction between nitric oxide and oxygen free radicals. SUMMARY BACKGROUND DATA: Nitric oxide and oxygen free radicals are involved in the pathophysiology of acute pancreatitis. It is well established that oxygen free radicals play an important role in the development of pancreatic cell damage and remote organ failure, but the impact of nitric oxide on the disease process and the interactions between the two radical species remain controversial. METHODS: Necrotizing pancreatitis (NP) was induced in Wistar rats by intraductal sodium taurocholate infusion after pretreatment with isotonic saline (NP-S), superoxide dismutase/catalase (NP-SOD/CAT), or an anti-ICAM-1 antibody (aICAM-1). Sham-operated rats received isotonic saline (SHX). After an observation period of 5 minutes and 24 hours, the pancreas was removed for microscopy, glutathione, and myeloperoxidase (MPO) analysis. The inducible NO synthase (NOS-2) was detected by Western blotting or RT-PCR. Serum was analyzed for nitrite/nitrate (NO2-/NO3-) and S-nitrosothioles (RSNO), while plasma was used to assay for trypsinogen activation peptides (TAP). RESULTS: NP-S animals showed a significant decrease in GSH levels after NP-induction as compared with animals under therapy. Increased MPO levels in the NP-S group were significantly reduced by aICAM-1 while SOD/CAT injection showed no changes. Serum NO-derivatives peaked at 12 hours while TAP levels had a maximum at 6 hours after NP induction, and were lower after aICAM-1 application SOD/CAT treatment increased both parameters. Extended acinar cell damage and inflammatory infiltrate developed in NP-S animals and was significantly improved by SOD/CAT and aICAM-1 treatment. RT-PCR and Western-blot analysis revealed NOS-2 expression in the NP-S group, which was reduced by radical scavengers and aICAM-1. CONCLUSION: Enhanced nitric oxide synthase expression and increased nitric oxide derivatives are found during severe acute pancreatitis. Oxygen free radicals and neutrophils seem to be potent and important regulation mechanisms for nitric oxide synthase activity and nitric oxide-mediated toxicity but imply only a secondary role for nitric oxide in the local pathologic mechanism of this disease.

Animals↗

Distributional and functional alterations of immunocompetent peripheral blood lymphocytes in patients with chronic pancreatitis.

OBJECTIVE: To investigate whether the chronic inflammatory process in patients with chronic pancreatitis affects their immune function. SUMMARY BACKGROUND DATA: Chronic pancreatitis is a chronic inflammatory disease of the exocrine pancreas. In approximately 30% of patients, an inflammatory mass of the pancreatic head is found, representing an indication for surgery. METHODS: This study comprised 28 patients with chronic pancreatitis. Sixteen patients were also reevaluated 1 year after resection of the pancreatic head for chronic pancreatitis. RESULTS: Compared with an age- and gender-matched control group, the number of CD3(+) cells was significantly increased in patients with chronic pancreatitis, with an increase of both CD3(+)CD4(+) and CD3(+)CD8(+) cells. The number of natural killer cells or B lymphocytes did not differ between the patients and the control group. After stimulation with phytohemagglutinin or anti-CD3 antibodies, the blastogenic response was significantly attenuated in the patients with chronic pancreatitis. One year after resection of the pancreatic head for chronic pancreatitis, the distribution and the blastogenic response to phytohemagglutinin and anti-CD3 antibodies had returned to normal compared with preoperative values. CONCLUSION: The chronic inflammatory process in chronic pancreatitis markedly affects the distribution and function of peripheral immunocompetent blood cells, and elimination of the chronic inflammatory focus by pancreatic head resection restores the suppressed immune function in these patients.

Adult↗

Influence of resection margins on survival for patients with pancreatic cancer treated by adjuvant chemoradiation and/or chemotherapy in the ESPAC-1 randomized controlled trial.

OBJECTIVE: To assess the influence of resection margins on survival for patients with resected pancreatic cancer treated within the context of the adjuvant European Study Group for Pancreatic Cancer-1 (ESPAC-1) study. SUMMARY BACKGROUND DATA: Pancreatic cancer is associated with a poor long-term survival rate of only 10% to 15% after resection. Patients with positive microscopic resection margins (R1) have a worse survival, but it is not known how they fare in adjuvant studies. METHODS: ESPAC-1, the largest randomized adjuvant study of resectable pancreatic cancer ever performed, set out to look at the roles of chemoradiation and chemotherapy. Randomization was stratified prospectively by resection margin status. RESULTS: Of 541 patients with a median follow-up of 10 months, 101 (19%) had R1 resections. Resection margin status was confirmed as an influential prognostic factor, with a median survival of 10.9 months for R1 versus 16.9 months months for patients with R0 margins. Resection margin status remained an independent factor in a Cox proportional hazards model only in the absence of tumor grade and nodal status. There was a survival benefit for chemotherapy but not chemoradiation, irrespective of R0/R1 status. The median survival was 19.7 months with chemotherapy versus 14.0 months without. For patients with R0 margins, chemotherapy produced longer survival compared with to no chemotherapy. This difference was less apparent for the smaller subgroup of R1 patients, but there was no significant heterogeneity between the R0 and R1 groups. CONCLUSIONS: Resection margin-positive pancreatic tumors represent a biologically more aggressive cancer; these patients benefit from resection and adjuvant chemotherapy but not chemoradiation. The magnitude of benefit for chemotherapy treatment is reduced for patients with R1 margins versus those with R0 margins. Patients with R1 tumors should be included in future trials of adjuvant treatments and randomization and analysis should be stratified by this significant prognostic factor.

Adenocarcinoma↗

Clinical relevance of caspase-1 activated cytokines in acute pancreatitis: high correlation of serum interleukin-18 with pancreatic necrosis and systemic complications.

OBJECTIVES: There is recent experimental evidence that caspase-1 activation plays an instrumental role in the pathomechanism of severe acute pancreatitis. Besides interleukin-1beta, interleukin-18, a recently described proinflammatory cytokine, is cleaved into its biologically active form by caspase-1 as well. Interleukin-18 is known to have potent properties concerning the activation of the Th1-lymphocyte subset via costimulation of interferon-gamma production. In contrast to interleukin-1beta, little is known about the clinical impact of interleukin-18 in the course of acute pancreatitis. DESIGN: Cohort study comparing patients with mild and severe acute pancreatitis associated with local and systemic complications during the course of the disease. SETTING: Surgical and anesthesiological intensive care unit as well as wards of the department of general surgery. PATIENTS: We included 68 patients with acute pancreatitis in the present study. In terms of local complications, pancreatic necrosis was present in 37 patients, of whom 21 developed pancreatic infections. Systemic complications included pulmonary, renal, or cardiocirculatory insufficiency and were observed in 40, 18, and 25 patients, respectively. Severe multiple-organ dysfunction syndrome involving all three organ systems occurred in 18 patients, all suffering from pancreatic necrosis. INTERVENTIONS: Serum samples were collected over 14 consecutive days after study inclusion. Ascites or peripancreatic exudate was obtained by ultrasound-guided fine needle aspiration in 14 cases. Sera and local aspirates were stored at -70 degrees C until analysis. MEASUREMENTS AND RESULTS: Interleukin-18 and interferon-gamma were measured by commercially available enzyme-linked immunosorbent assays. Interleukin-18 concentrations were significantly increased after the fourth day of disease onset until the end of the observation period in patients who developed pancreatic necrosis and systemic complications such as pulmonary, renal, and cardiocirculatory failure as well as severe multiple-organ dysfunction syndrome. However, no correlation was found between the development of pancreatic infections and interleukin-18 concentrations. In contrast with interleukin-18, interferon-gamma concentrations did not show any significant difference with respect to the presence or absence of either systemic or local complications. Local interleukin-18 concentrations in ascites or peripancreatic exudate were up to 20-fold higher than systemic concentrations, whereas interferon-gamma concentrations did not differ. CONCLUSIONS: Serum interleukin-18 concentrations are significantly elevated in patients with acute pancreatitis complicated by pancreatic necrosis and remote organ failure. The present data suggest an important role of caspase-1 dependent cytokine activation in the pathomechanism of severe acute pancreatitis beyond the experimental setting. In this context, interleukin-18 may serve as a potential target for new therapeutic approaches.

APACHE↗

Reduced serum total reductive capacity in lethal severe trauma.

BACKGROUND: Risk assessment is a prerequisite for effective treatment and triage in severe injury. A novel substrate-based assay to measure total reductive capacity (TORC) in serum was used to stratify risk of lethal outcome in severe trauma in a clinical trial. METHODS: Serum of patients with severe trauma (Injury Severity Score > 19) was obtained at the accident site, at admission, and at regular intervals thereafter. TORC was determined and correlated to outcome. The TORC assay uses thiol-labeled arachidonic acid as substrate from which free thiols are released by reductive amino acids and the specific activity of phospholipase A2. Free thiols are coupled to monochrombimone, and the resulting fluorescence is proportional to TORC. RESULTS: Eighteen patients with lethal severe trauma and 16 patients who survived were studied. Injury Severity Scores (lethal, 33 (29--43); survival, 31 (25--42); p = NS) and Polytrauma Scores (lethal, 25 [18--32]; survival, 26 [23--31], p = NS) were not significantly different. At the accident site, patients with a lethal course had significantly lower TORC than nonlethal cases (59.2 +/- 5.1 ng/mL vs. 89.5 +/- 6.7 ng/mL; p < 0.001). Values at admission were similar (lethal, 51.2 +/- 7 ng/mL; survival, 73.8 +/- 9 ng/mL; p < 0.01). At the accident site and at admission, TORC < 82.3 ng/mL was prognostic of lethal outcome (sensitivity, 88%; specificity, 65%/73% and 69%, respectively, for admission). CONCLUSION: Serum reductive potential at the site of accident or at admission allows the stratification of trauma patients with respect to lethal outcome in severe trauma when severity scores fail to do so.

Adolescent↗

Early severe acute pancreatitis: characteristics of a new subgroup.

This study focuses on patients with severe acute pancreatitis complicated by organ failure within the initial phase of the disease. Data of 158 patients with severe acute pancreatitis (SAP) admitted to hospital within 72 hours after onset of symptoms were prospectively documented and analyzed for the occurrence of early severe acute pancreatitis (ESAP). ESAP was defined as presence of organ failure (OF) at admission. Forty-seven (30%) patients had ESAP, compared with 111 patients without OF (SAP group). In a multivariate analysis, the main factor predisposing to ESAP was the presence of extended pancreatic necrosis (odds ratio, 3.8), whereas biliary pancreatitis was associated with a slightly lower risk compared with alcoholic pancreatitis (odds ratio, 0.34). Compared with SAP, patients with ESAP more frequently developed intractable organ failure, which posed the indication for surgical treatment. Surgical necrosectomy due to progressive OF had to be performed in 89% of the ESAP patients and in 60% of the SAP patients. The incidence of infected pancreatic necrosis did not differ between both groups (23 vs. 21%). Mortality was significantly higher in ESAP (42 vs. 14%; p = 0.0003). ESAP is characterized by the presence of extended pancreatic necrosis and a complicated clinical course. Intractable organ failure is a frequent finding. Given the poor prognosis of ESAP, these patients should be treated in specialized intensive care units.

Acute Disease↗

Overexpression of caspase-1 (interleukin-1beta converting enzyme) in chronic pancreatitis and its participation in apoptosis and proliferation.

Caspase-1, formerly designated interleukin-1beta converting enzyme, was the first described member of a group of cysteine proteases called caspases. It is suggested that caspases play an important role in apoptosis, but recent observations could show that caspase-1 might also be involved in cellular proliferation. We investigated the expression of caspase-1 in 38 chronic pancreatitis tissues, six pancreatitis tissues from patients with pancreatic carcinoma and nine normal pancreatic tissues by immunohistochemistry. Western blot analysis was used to confirm the immunohistochemical findings. We found a clear expression of caspase-1 in chronic pancreatitis, but not in normal pancreatic tissues. Interestingly, we found expression of caspase-1 in three distinct morphologic compartments: (i) in atrophic acinar cells (31 of 35; 89%), (ii) proliferating cells of ductal origin (33 of 38; 87%), and (iii) in acinar cells redifferentiating to form tubular structures (26 of 31; 83%). These immunohistochemical findings were confirmed by Western blot analysis, which showed an expression of caspase-1 in 85% of the tissues. No correlation was found between any of the examined clinicopathologic features and the caspase-1 expression in chronic pancreatitis. In conclusion, the expression of caspase-1 is a frequent event in chronic pancreatitis and its distribution pattern may reflect two functions of this protease: on one hand its participation in the apoptotic pathway in atrophic acinar cells and, on the other hand, its role in proliferation and differentiation in proliferating duct cells.

Adult↗