Randomized clinical trial of the effect of a fibrin sealant patch on pancreatic fistula formation after pancreatoduodenectomy.

BACKGROUND: The potential for a fibrin sealant patch to reduce the risk of postoperative pancreatic fistula (POPF) remains uncertain. The aim of this study was to evaluate whether a fibrin sealant patch is able to reduce POPF in patients undergoing pancreatoduodenectomy with pancreatojejunostomy. METHODS: In this multicentre trial, patients undergoing pancreatoduodenectomy were randomized to receive either a fibrin patch (patch group) or no patch (control group), and stratified by gland texture, pancreatic duct size and neoadjuvant treatment. The primary endpoint was POPF. Secondary endpoints included complications, drain-related factors and duration of hospital stay. Risk factors for POPF were identified by logistic regression analysis. RESULTS: A total of 142 patients were enrolled. Forty-five of 71 patients (63 per cent) in the patch group and 40 of 71 (56 per cent) in the control group developed biochemical leakage or POPF (P = 0·392). Fistulas were classified as grade B or C in 16 (23 per cent) and ten (14 per cent) patients respectively (P = 0·277). There were no differences in postoperative complications (54 patients in patch group and 50 in control group; P = 0·839), drain amylase concentration (P = 0·494), time until drain removal (mean(s.d.) 11·6(1·0) versus 13·3(1·3) days; P = 0·613), fistula closure (17·6(2·2) versus 16·5(2·1) days; P = 0·740) and duration of hospital stay (22·1(2·2) versus 18·2(0·9) days; P = 0·810) between the two groups. Multivariable logistic regression analysis confirmed that obesity (odds ratio (OR) 5·28, 95 per cent c.i. 1·20 to 23·18; P = 0·027), soft gland texture (OR 9·86, 3·41 to 28·54; P < 0·001) and a small duct (OR 5·50, 1·84 to 16·44; P = 0·002) were significant risk factors for POPF. A patch did not reduce the incidence of POPF in patients at higher risk. CONCLUSION: The use of a fibrin sealant patch did not reduce the occurrence of POPF and complications after pancreatoduodenectomy with pancreatojejunostomy. Registration number: 2013-000639-29 (EudraCT register).

Hospitalization, frequency of interventions, and quality of life after endoscopic, surgical, or conservative treatment in patients with chronic pancreatitis.

OBJECTIVE: Patients with chronic pancreatitis usually have a long and debilitating history of disease with frequent hospital admissions, episodes of intractable pain and multiple interventions. The sequences of treatment at initial presentation, endoscopy, surgery, or conservative treatment may affect the time course and admissions needed for disease control, thereby determining quality of life and overall outcome. METHODS: A total of 292 patients with initial endoscopic, surgical, or conservative pharmacological treatment were retrospectively analyzed regarding frequency of interventions, days in hospital, symptom-free intervals, morbidity, and mortality. Quality of life (QoL) at the latest follow-up was measured by two standardized quality of life questionnaires (EORTC C30 and PAN26). RESULTS: Endoscopic treatment was initially performed in 150 (51.4%) patients, whereas 99 (33.9%) underwent surgery and 43 (14.7%) patients were treated conservatively at their initial presentation. Patients who underwent surgery had a significantly shorter time in the hospital (25.3 ± 24.6, 34.4 ± 35.1, 61.1 ± 37.9; P < 0.001), fewer subsequent therapies (0.43 ± 1.0, 2.1 ± 2.4, 3.1 ± 3.0; P ≤ 0.001), and a longer relapse-free interval (P = 0.004) compared with endoscopically treated patients. The overall complication rate was 32% both after surgery and endoscopy. Infectious-related complications occurred more often after surgical treatment (P ≤ 0.001), whereas patients after endoscopic intervention developed acute or chronic pancreatitis or pseudocyst formation (P = 0.023). CONCLUSIONS: Patients who undergo surgery as their initial treatment for chronic pancreatitis require less consecutive interventions, a shorter hospital stay, and have a better quality of life compared with any other treatment. Surgery should therefore be considered early for the treatment of chronic pancreatitis, when endoscopic or conservative treatment fails and patients require further intervention.

[Vacuum therapy--basics, indication, contraindication and cost listing]. / Vakuumversiegelung--Grundlagen, Indikationen, Kontraindikationen und Kostenbilanz.

Vacuum therapy is an efficient alternative to conservative wound care and creates new possibilities for the treatment of a variety of chronic and acute wounds. Already more than two thousand years ago vacuum treatment was applied in traditional Chinese medicine and also today vacuum therapy is used more and more frequently in daily clinical practice. The positive effects of the therapy are based on the stimulation of blood flow, formation of granulation tissue, angiogenesis, as well as cell proliferation, accelerated secondary wound closure and the removal of bacteria from the wound. As can be demonstrated based on a clinical picture of the open abdomen, vacuum therapy based on KCI's (Kinetic Concepts Inc) VA.C. system (Vacuum Assisted Closure) provides a possibility for not only accelerating the healing process, but also significantly lowering mortality. Since vacuum therapy in the form of the V.A.C. system represents a relatively expensive intervention, a comparison with conventional healing methods is demonstrated. Clinical studies with high evidence level show that both economic and clinical advantages of the vacuum therapy speak for its application. Savings with respect to the faster healing rates, the reduced dressing changes, as well as hospital stay and the care requirements, and the reduction of subsequent illnesses, compensate for the higher initial costs. Although many reports exist on treatment successes with the application of V.A.C. therapy, there are several cases for which vacuum therapy is contraindicated. In order to make sure that V.A.C. therapy is effective, a range of precautions and contraindications are described. The European Wound management Association (EWMA) just wrote a position paper on V.A.C. therapy. This is available at www.ewma.org.

Straight and colonic J-pouch reconstruction after low anterior resection.

PURPOSE: A complication after restorative rectal surgery with a straight anastomosis is low-anterior resection syndrome with a postoperatively deteriorated anorectal function. The colonic J-reservoir is sometimes used with the purpose of reducing these symptoms. An alternative method is to use a simple side-to-end anastomosis or a coloplasty. MATERIAL AND METHODS: Three-hundred fiftyseven patients with rectal cancer undergoing total mesorectal excision (TME). Three-hundred (84.0%) received a low anterior resection with primary anastomosis and colo-rectal n = 194 (64.6%) or colo-anal anastomosis n = 106 (35.3%). A colonic pouch using the descending colon was created in 24 patients and in 75 patients respectively. Surgical results and complications were recorded. Patients were followed with a functional evaluation at 6 and 12 months postoperatively. RESULTS: Patient characteristics in both groups were very similar regarding gender, age, tumor level, and Dukes' stages. A large proportion of the patients received short-term preoperative radiotherapy (72%). There was no significant difference in surgical outcome between the 2 techniques with respect to anastomotic height, perioperative blood loss, postoperative complications, reoperations, hospital stay or pelvic sepsis rates except the anastomotic stricture rate in the colonic J-Pouch group after coloanal anastomosis (p < 0.02). CONCLUSIONS: These data show that either a colonic J-pouch or a straight anastomosis performed on the descending colon in low-anterior resection with TME are methods that can be used with similar expected surgical and functional results.

[Colo-anal anastomosis: improvement of early function outcome by reconstruction with the colonic pouch]. / Coloanale Anastomose: Verbesserung der funktionellen Frühergebnisse durch Rekonstruktion mit Colonpouch.

INTRODUCTION: Early functional outcome after ultra-low anterior resection with coloanal anastomosis (CAA) may be improved by construction of a colonic pouch. The aim of this prospective observational study was to compare results of colonic pouch-anal anastomosis (CPAA) with conventional CAA including the learning curve. METHODS: From February 1996 through May 1998, 45 consecutive patients underwent CAA or CPAA following radical rectal resection for cancer. The technique of resection was identical in both groups, and all patients received a diverting stoma. The colonic pouch was constructed using linear staplers. Three and 12 months following stoma closure subjective continence and bowel habits were assessed; anal manometry was performed at 3 months. RESULTS: 20 patients with CPAA (9 F, 11 M, age 62 +/- 9 years) were compared to 25 CAA patients (11 f, 14 m, age 64 +/- 10 years). There was no mortality, and morbidity was comparable between groups. Three months following stoma closure, in the CPAA group bowel frequency was significantly diminished (1.4 vs 5.8; P < 0.0001), fewer patients had liquid motions (0/20 vs 12/25 patients; P < 0.0001), and more were continent (20/20 vs 4/25; P < 0.001) and able to defer defaecation (20/20 vs 2/25; P < 0.0001). Functional anal canal length was significantly shorter in CPAA patients (2.9 vs 3.5 cm; P < 0.008). Although at 12 months follow-up continence had improved in patients with CAA, bowel frequency (2.5 vs 1.3; P < 0.002), and number of patients with liquid motions (10/25 vs 0/20; P < 0.007) and passive incontinence (12/25 vs 0/20; P < 0.0001) were still significantly higher than the CPAA group. CONCLUSION: Even including the learning curve, CPAA may yield superior functional results at 3 months and 1 year compared to conventional CAA without increasing morbidity.

The role of Kupffer cell inhibition in porcine endotoxemia.

The selective Kupffer cell inhibitor gadolinium chloride (GdCl3) has been demonstrated to protect animals from lethality in experimental endotoxemia and sepsis in rodent models. This study was designed to investigate the effect of Kupffer cell blockade on the early response to endotoxin in a large animal model. Using a porcine endotoxemia model, animals were randomized to receive either GdCl3 (10 mg/kg or 30 mg/kg; n = 8 in each group) or vehicle saline (n = 8) 24 h before exposure to endotoxin. Pretreatment with GdCl3 resulted in a dose dependent reduction in early hepatic oxygen consumption as well as oxygen extraction ratio in response to continuous infusion of endotoxin. At 5 h there was significant lower serum AST level in animals given 30 mg/kg of GdCl3 as compared to the two other groups. Pretreatment with GdCl3 induced a dose dependent reduction of Kupffer cells in the liver sinusoids. Despite this, all animals deteriorated with continuous infusion of endotoxin as evidenced by the progressive reduction in cardiac output, mean arterial pressure and total liver blood flow. Also, increases in pulmonary arterial pressure, portal venous pressure and systemic, pulmonary and hepatic vascular resistance were seen. This is consistent with activation of other cell populations and defense mechanisms by endotoxin, perpetuating the septic response. However, modulation of reticuloendothelial cell function seems feasible also in larger animals, and our results stimulate to further research on potential immunomodulatory tools in early sepsis.

Lipopolysaccharide causes atrophy of Peyer's patches and an increased expression of CD28 and B7 costimulatory ligands.

Intestinal mucosal dysfunction appears to contribute to infectious complications in critically ill patients. The current study was undertaken to investigate whether endotoxin affects lymphocyte subpopulations and the expression of costimulatory signals in Peyer's patches (PP). Female Balb/c mice were given an intraperitoneal injection of 25 microg LPS and sacrified 24 h or 72 h later to determine total cell yield, lymphocyte subpopulations (B-cells, total T-cells, CD4+- and CD8+-cells), the costimulatory molecules CD28, B7.1 (CD80) and B7.2 (CD86) and the percentage of apoptotic cells in PP and in the spleen as well as small intestinal IgA concentration. Lipopolysaccharide (LPS) challenge caused a significant decrease of total cell yield in PP at both time-points (-50+/-28% and -43+/-25%, respectively; P < 0.001). This decrease was significant for all measured lymphocyte subpopulations. In contrast, total cell yield was increased (P < 0.001) in the spleen 24 h (+52+/-13%) and 72 h (+130+/-22%) after LPS. The decrease of lymphocyte numbers in the PP was accompanied by an increased percentage of lymphocytes expressing costimulatory molecules. In this respect, an increased percentage of CD40+CD80+, CD40+CD86+, and of CD4+CD28+ could be demonstrated after LPS administration. In the spleen, the percentage of CD4+CD28+ was also elevated after LPS bolus, however, the percentage of CD40+CD80+ was reduced, and that of CD40+CD86+ was unaltered. The influence of LPS on apoptosis of lymphocytes was time-dependent. The percentage of apoptotic cells 24 h after LPS was increased in PP (P < 0.01), but was unchanged in the spleen. Seventy-two hours after LPS injection, the percentage of apoptotic cells returned to normal in PP. Luminal IgA levels remained unchanged after LPS challenge. In conclusion, our data show that LPS causes atrophy of PP which seems to be counterregulated by an enhanced expression of costimulatory molecules.

Candida infection of local necrosis in severe acute pancreatitis is associated with increased mortality.

The aim of this study was to evaluate the frequency of Candida infection of pancreatic necrosis in patients suffering from severe acute pancreatitis (SAP) and to analyze its impact on the outcome. Two-hundred and fifty consecutive patients with SAP from January 1986 to December 1998 were studied retrospectively. Their mean APACHE II score at the day of admission was in 16.1 (range 8-35). All patients were in need of operative therapy. Overall mortality was 38.8% (97 patients). One-hundred and eighty-two patients (72.8%) suffered from local infected necrosis. Among these patients, local Candida infection was observed in 31 patients, whereof 23 patients (74%) suffered from local fungal infection detected at first operation. During the course of disease, 12 patients (39%) also revealed fungemia. Local Candida infection as compared to no Candida infection was associated with an increased mortality rate (84% vs. 32%; P 0.0001). Multivariate logistic regression analysis identified APACHE II score (P < 0.0001), age of the patient (P < 0.003), extent of pancreatic necrosis (P < 0.002), and local bacterial (P < 0.04) and fungal infection (P < 0.004) as independent factors significantly contributing to mortality. SAP, requiring surgical treatment, is associated with high in-hospital mortality. Patients suffering from local Candida infection are at high risk of fatal outcome.

Severe acute pancreatitis causes alterations in HLA-DR and CD14 expression on peripheral blood monocytes independently of surgical treatment.

OBJECTIVE: To find out if the severity of acute pancreatitis or the surgical treatment of severe acute pancreatitis influences HLA-DR and CD14 expression on peripheral blood monocytes. DESIGN: Prospective open study. SETTING: University hospital, Austria. SUBJECTS: 9 consecutive patients with severe acute pancreatitis in need of operative treatment, 5 patients with mild acute pancreatitis, and 7 healthy volunteers. INTERVENTIONS: Samples of 5 ml blood were taken daily into endotoxin free tubes at same time points. Surgical treatment for severe acute pancreatitis consisted of blunt necrosectomy, operative lavage, laparostomy, and open drainage. MAIN OUTCOME MEASURES: Correlation between HLA-DR and CD14 expression on peripheral blood monocytes on the one hand and the severity of acute pancreatitis and operative treatment of severe acute pancreatitis, on the other. RESULTS: In patients with severe acute pancreatitis expression of HLA-DR and CD14 was significantly downregulated both before and after operation (p < 0.0001; ANOVA), compared with patients with mild acute pancreatitis or healthy controls. However the expression of the two cell surface markers was not affected either by the first operation, or by the reoperations. CONCLUSION: These findings suggest that in acute pancreatitis the expression of cell surface markers on peripheral blood monocytes is related to the severity of disease but is not influenced by operative treatment.

[Value of punch biopsy in diagnosis of palpable breast tumors. A prospective analysis of 150 patients]. / Die Wertigkeit der Stanzbiopsie in der Diagnostik palpabler Brusttumoren. Eine prospektive Analyse von 150 Patienten.

To reduce the need for excisional biopsies in the diagnosis of breast masses, the accuracy of core needle biopsy (CNB) was determined in a university hospital setting. 150 consecutive women with solitary palpable breast masses underwent CNB over a 2-year period. Histological diagnosis was established, and in the case of cancer the type, grade and estrogen and progesterone receptors were determined. CNB findings were compared with those independently obtained from the subsequently excised lesions. There were 103 malignant and 47 benign lesions. CNB diagnosed 136 lesions (90.7%) correctly. Fourteen biopsies were inconclusive. Histological type was correct in all cases and grading in 83.5%. Correct hormone receptor status was obtained in 97.1% of cases for estrogen and 91.3% for progesterone. Diagnosis of histological type, grading, and hormone receptors obtained from CNB material is a safe way to analyze palpable breast lesions and therefore a useful tool to select patients for preoperative treatment.

Early effects of catecholamine therapy on mucosal integrity, intestinal blood flow, and oxygen metabolism in porcine endotoxin shock.

OBJECTIVE: To determine the early effects of therapy of endotoxin (ET) shock with epinephrine, norepinephrine, or dopexamine on splanchnic circulation, oxygen metabolism, sigmoid mucosal pHi, bacterial translocation, and morphologic integrity of the ileal, colonic, and sigmoid mucosa. SUMMARY BACKGROUND DATA: Conflicting concepts exist concerning the catecholamine therapy of septic shock, but little is known about the effects of catecholamine treatment on splanchnic circulation and mucosal integrity. METHODS: ET shock was induced in pigs by ET infusion over 30 minutes, and animals were studied for 4 hours. All animals were resuscitated with fluid. To mimic the treatment of septic shock in humans, mean arterial pressure was maintained in two groups at >70 mm Hg with the administration of epinephrine or norepinephrine. A third group of animals received dopexamine at 7 microg/kg per minute. Systemic and splanchnic blood flow and oxygen metabolism were studied, sigmoid colon mucosal pHi was obtained tonometrically, and bacterial translocation was determined by culture of portal venous blood, mesenteric lymph nodes, liver, spleen, and lung specimens. Histologic sections of ileal, colonic, and sigmoid mucosa were morphometrically examined for therapy effects. RESULTS: All investigated catecholamines increased cardiac output and systemic oxygen delivery, whereas intestinal blood flow and oxygen delivery remained unchanged. Sigmoid mucosal pHi decreased in all study animals, but the decrease was most pronounced in the epinephrine group. Pigs receiving epinephrine also showed >40% damage of the mucosa of the ileum and colon, whereas animals receiving ET alone, norepinephrine, or dopexamine showed only moderate lesions with signs of restitution. No animal showed bacterial translocation. CONCLUSIONS: Systemic hemodynamics and oxygen metabolism data do not reflect intestinal perfusion. Norepinephrine or dopexamine administration in ET shock causes no additional impairment of intestinal integrity. Epinephrine therapy, in contrast, is associated with a significant reduction of mucosal pHi and considerable early mucosal damage. Its application in septic shock is hazardous.

Receptor and non-receptor mediated formation of superoxide anion and hydrogen peroxide in neutrophils of intensive care patients.

Generation of reactive oxygen intermediates (ROI) has been implicated in tissue damage in a variety of disease states including sepsis and trauma. On the other hand, generation of ROI in polymorphonuclear granulocytes (PMN) presents a crucial element in the defence of the host against invading microorganisms. In the present study we investigated the generation of superoxide anions (O2-) and hydrogen peroxide (H2O2) by neutrophils (PMN)5 of 17 critically ill patients treated at a intensive care unit (ICU) after polytrauma (n = 6), heart operation (n = 6) or during septic shock (n = 5) using flow cytometry. O2- production of PMN from ICU patients was significantly lower (p < 0.01) than that in healthy volunteers (HV) during non-receptor mediated stimulation with phorbol-myristate-acetate (PMA) but higher (p < 0.001) during receptor mediated stimulation with formylmethionine-leucine-phenylalanine (FMLP). H2O2 generation of PMN from ICU patients was increased after stimulation with FMLP (p < 0.01) and remained unchanged after stimulation with PMA. Patients in septic shock had lower O2(-)-generation of PMN than did injured patients and patients after heart operations. We conclude that receptor mediated formation of O2- and H2O2 is stimulated in ICU patients. However, in patients in septic shock O2(-)-generation decreases, which potentially might contribute to the immunoparalysis present in septic shock.

Does reoperation for abdominal sepsis enhance the inflammatory host response?

OBJECTIVE: To determine the effect of reoperation for severe abdominal sepsis on the course of proinflammatory mediators and hemodynamic factors. DESIGN: Inception cohort. SETTING: A university hospital and a secondary care hospital. PATIENTS AND METHODS: Fifteen patients suffering from severe peritonitis due to intestinal perforation or infected necrotizing pancreatitis were studied following 19 subsequent operations. Plasma samples were obtained immediately before and after reoperation, as well as at 1, 3, 6, 12, and 24 hours after operation to determine endotoxin, tumor necrosis factor alpha, and interleukin-6 levels. Clinical factors and therapeutic support were recorded at the corresponding times. MAIN OUTCOME MEASURES: Postoperative hemodynamic instability as defined by changes of the mean arterial pressure, pulmonary capillary wedge pressure, and vasopressor support. Courses of proinflammatory mediators were correlated to the hemodynamic findings. RESULTS: Mean arterial pressure decreased from 94 mm Hg postoperatively to 80 mm Hg at 3 hours (P = .006) and 81 mm Hg at 6 hours postoperatively (P = .005). Pulmonary capillary wedge pressure dropped from 14 mm Hg postoperatively to 12 mm Hg at 1 hour (P = .05). Vasopressor support significantly increased from 1 to 6 hours postoperatively (P = .02). Neither endotoxin nor tumor necrosis factor alpha levels showed significant changes in the postoperative course. Interleukin-6 levels continously increased from 586 pg/mL preoperatively to 910 pg/mL at 1 hour (P = .02) and 931 pg/mL at 3 hours postoperatively (P = .04). Overall interleukin-6 levels (R = -0.38, P = .003) and especially early postoperative interleukin-6 levels inversely correlated with postoperative mean arterial pressure. CONCLUSIONS: Reoperation for abdominal sepsis frequently causes substantial hypotension, and is, thus, potentially harmful to the patient. Reoperative trauma may induce an early postoperative increase in interleukin-6 levels. Because this increase occurs before the development of hypotension, a relationship between the kinetics of this cytokine and the observed hemodynamic instability may be present.

[Early postoperative infections after liver transplantation--pathogen spectrum and risk factors]. / Frühe postoperative Infektionen nach Lebertransplantation--Keimspektrum und Risikofaktoren.

Infections occurring during the early postoperative phase after liver transplantation result in a significant rise in morbidity and mortality. The records of 279 orthoptic transplantations performed in 248 patients were analyzed retrospectively. 55.6% of all patients suffered from one or more episodes of bacterial and/or fungal infection during their postoperative hospitalisation. The median onset of bacterial/fungal infection was on day 7 after transplantation. Enterococci (42 episodes), Pseudomonas aeruginosa (38 episodes), staphylococci (37 episodes), Escherichia coli (17 episodes) and Candida albicans (11 episodes) were the most frequently detected organisms. 74 (29.8%) patients developed viral infections. 20 patients (8.1%) showed infection with cytomegalovirus (CMV), 32 patients (12.9%) with herpes simplex virus (HSV) and 6 patients (2.4%) with varicella zoster virus (VZV). 14 patients (5.6%) developed infection with both CMV and VZV. Triple infection with CMV, HSV and VZV occurred in one patient. Statistical analysis of potential risk factors showed a significant influence of blood volume replacement (p < 0.001) and occurrence of at least one rejection period (p < 0.02) for major bacterial/fungal infection and immunosuppression (p < 0.001), cold ischemic time (p < 0.04), occurrence of at least one rejection period (p < 0.005) and blood volume replacement (p < 0.04) for viral infection.

The importance of the effect of underlying disease on rejection outcomes following orthotopic liver transplantation.

Despite major advances in immunopharmacology, virtually all patients receive the same center-specific immunosuppressive regimen following orthotopic liver transplantation (OLT). The present analysis was performed on the hypothesis that the original disease representing the indication for OLT leads to a different initial immunological situation of the patient. The type of original disease might therefore be a predisposing factor for acute rejection episodes and influence graft and patient survival. From January 1988 to July 1994, 34 patients received OLT at our institution for end-stage primary biliary cirrhosis (group 1) and 66 patients for end-stage alcoholic cirrhosis (group 2). Overall survivals at 1 and 5 years in group 1 versus group 2 were 67% versus 80% and 50% versus 68%, respectively (P<0.04). Retransplantation was performed in 21% of patients from group 1 and in 6% from group 2. The estimated risk for freedom from acute rejection amounts to 38% in group 1 compared with 59% in group 2 (P<0.02). Multivariate regression analysis of potential risk factors identified only the underlying disease as independent predictor. Analysis of cumulative rates of clinically relevant rejection episodes stratified by group revealed 0.29 and 0.05 episodes per patient at one month and 0.80 and 0.06 at six months (P<0.009) respectively. In our clinical experience it was possible to confirm the hypothesis that the underlying disease is the reason for a significantly different incidence of acute rejection episodes and that it subsequently influences graft and patient survival. This approach to an individually adapted immunosuppressive therapy should be taken into consideration and other appropriate parameters investigated.

Safety and efficacy of increasing dosages of glycyl-glutamine for total parenteral nutrition in polytrauma patients.

Supplementation of parenteral nutrition with glutamine (GLN) has been suggested to improve the efficacy of nutritional support by stimulating protein synthesis and improving immunocompetence. In the present study we investigated the impact of infusing the dipeptide glycyl-glutamine (GLY-GLN) at increasing dosages on plasma amino acid concentrations in patients with polytrauma. Nine polytraumatized patients were randomly assigned according their age and their trauma score to three experimental groups. Group 1 received 280, group II 450, and group III 570 mg GLY-GLN per kg body weight/day for a period of four days (3rd to 7th posttraumatic day), resulting in a maximum daily GLN administration (calculated for a 70 kg patient) of 14 g, 21 g and 28 g, respectively. Seven polytraumatized patients receiving the nutrition solution without GLY-GLN supplementation served as controls. All patients received total parenteral nutrition with an average amino acid administration of 1.1 g/kg/day and a total energy intake of 30 kcal/kg/day. GLY-GLN infusion did not evoke any side effects. In comparison with the control group, arterial plasma GLN concentrations increased significantly on day I after start of infusion in groups II and III, but remained raised throughout the study period only in group III (p < 0.003). Similarly, plasma GLY concentrations were also significantly raised in group III (p < 0.04). The maximum increase of plasma GLY was found on the second infusion day, after which plasma concentrations of GLY fell to concentrations even below those observed in the control group at the end of the study period. Excretion of GLY-GLN, GLN or GLY in the urine during the GLY-GLN infusions was negligible. We conclude from this first available dose finding study on glutamine-containing dipeptides that in polytraumatized patients infusion of 570 mg/kg/day of GLY-GLN (corresponding to 28 g glutamine or 40 g dipeptide/70 kg, respectively) is necessary to induce a sustained effect on plasma glutamine concentrations. No pathological accumulation of free glycine or of the dipeptide was seen with any of the three dosage steps of GLY-GLN. Thus, the administration of even high doses of GLY-GLN is feasible and safe in patients with polytrauma and is not associated with any relevant renal substrate loss.

[Revision of diffuse peritonitis: planned versus on demand]. / Revision bei diffuser Peritonitis: geplant v. on-demand.

Planned and "on-demand' reoperations are well-established concepts in the management of severe diffuse peritonitis. Both concepts were applied at our surgical department and reviewed with regard to specific complications and lethality. In the period between 1 January 1989 and 31 May 1994, 62 patients with the diagnosis of diffuse peritonitis underwent operative treatment at our surgical department. The mean age of the 29 female and 33 male patients was 58.2 years (range 17-93 years). The origin of peritonitis was the stomach in 8.1%, duodenum in 16.1%, small intestine in 12.9%, large intestine in 41.9% and the pancreas in 16.1%. Among these 62 patients, 15 were reoperated upon according to plan and 47 were reoperated upon on demand. The intraoperatively gained Mannheim peritonitis index and the Apache II score were similar in both groups. The average number of reoperations was five in the group of planned revisions and three in the group of on-demand revisions. Also lethality was similar in both groups. Regarding lethality, only the age of the patient (P < 0.03) and the preoperative Apache II score (P < 0.01) reached statistical significance. As expected, eradication of the infectious source was the precondition of survival regardless of the type of reoperation. Regarding our results, we conclude that planned or on-demand reoperations lead to similar results in the treatment of diffuse peritonitis. The crucial point for success is that elimination of the infection source take place as soon as possible.

Influence of glutamine on the phenotype and function of human monocytes.

Reduced concentrations of glutamine (GLN) in plasma and skeletal muscle, defective host defense systems, and a diminished expression of the HLA-DR antigen on monocytes are important diagnostic parameters for late post-injury sepsis. In this in vitro study, we investigated whether blood monocyte-derived macrophage antigen expression and function from healthy donors is influenced by GLN. Lowering the GLN concentration in culture medium from 2 mmol/L to 200 mumol/L reduced the expression of HLA-DR by 40% (P < .001) on monocyte-derived macrophages, and decreased tetanus toxoid-induced antigen presentation. In addition, low GLN levels downregulated the expression of intercellular adhesion molecule-1 (ICAM-1/CD54), Fc receptor for IgG (Fc gamma RI/CD64), and complement receptors type 3 (CR3; CD11b/CD18) and type 4 (CR4; CD11c/CD18). A correlation was found between the phagocytosis of IgG-sensitized ox erythrocytes or opsonized Escherichia coli and the decreased expression of Fc gamma RI and CR3. Monocyte expression of CD14, CD71, and Fc gamma RIII/CD16 and capacity to phagocytose latex beads were not affected by altering the level of GLN. Depletion of GLN was associated with a significant reduction in cellular adenosine triphosphate (ATP), which may have influenced cell surface marker expression and phagocytosis. It remains to be seen whether these in vitro findings are of clinical significance in the treatment of sepsis.

Necrosectomy and laparostomy--a combined therapeutic concept in acute necrotising pancreatitis.

OBJECTIVE: To present our experience with laparostomy and necrosectomy in the treatment of acute necrotising pancreatitis, and to show how refinements in our treatment regimen improved mortality over the years despite no reduction in the severity of the disease. DESIGN: Retrospective study. SETTING: University hospital, Austria. SUBJECTS: 125 patients treated by laparostomy/necrosectomy with repeated revisions during the period January 1983 to December 1991. INTERVENTIONS: Laparostomy, blunt necrosectomy, operative lavage, and open drainage. MAIN OUTCOME MEASURES: Mortality and morbidity. RESULTS: The severity of disease was assessed by the APACHE II score (median 15, range 4-30). In 106 of the 125 patients (85%) the necrotic pancreatic tissue was infected. Patients were operated on if they deteriorated clinically or if organ failure was suspected. A change in the protocol from revisions on demand (1983/4) to planned re-exploration at 48 hour intervals (1985/8) was associated with a reduction in mortality from 53% (16/30) to 28% (20/72). This was further reduced in 1989/91 to 17% (4/23) when a protocol of revisions planned for individual patients was introduced (p = 0.02). The incidence of gastrointestinal fistulas during the three periods was 6/30 (20%); 24/72 (33%); and 1/23 (4%); (p = 0.022), whereas that of intraabdominal bleeding remained much the same (7/23, 23%; 13/72, 18%; and 4/23, 17%; p = 0.56). The median (range) APACHE II scores for the three periods were 12 (4-27), 15 (5-30), and 14 (4-25). CONCLUSION: By continual revision of our protocol, together with accompanying improvements in intensive care, our mortality decreased significantly during the nine year period.