[Inguinal hernia operations-Always outpatient?] / Leistenhernienoperationen ­ immer ambulant?

Inguinal hernia operations represent the most frequent operations overall with 300,000 interventions annually in Germany, Austria and Switzerland (DACH region). Despite the announced political willingness and the increasing pressure from the legislator to avoid costly inpatient treatment by carrying out as many outpatient operations as possible, outpatient treatment has so far played a subordinate role in the DACH region. The Boards of the specialist societies the German Hernia Society (DHG), the Surgical Working Group Hernia (CAH of the DHG), the Austrian Hernia Society (ÖHG) and the Swiss Working Group Hernia Surgery (SAHC) make inroads into this problem, describe the initial position and assess the current situation.

Traumatic abdominal wall hernia diagnosed 14 years after a bad fall with lumbar spine fracture.

UNLABELLED: Traumatic abdominal wall hernias have significant implications for patients and insurance companies, especially when not been discovered at the time of trauma. We present the case of a gardener who sustained a bad fall during work in 1994 with immediate admission to the hospital for treatment. A fracture of the second lumbar spine body has been diagnosed and stabilized operatively. Postoperative computer tomography and magnetic resonance examinations demonstrated correct healing of the fracture. Neither the pain in the sacral spine, the left leg and left lower abdominal wall nor the sudden pain attacks in the groins with preference of the left groin stopped. Different neurologists considered as cause of the unchanged pain in the lower abdomen and left leg a radiculopathy in the lumbar spine. As a result of the neurological assessment the patient was operated in the lumbar spine (fixation of the fourth and fifth body) in a different hospital in 2007, unfortunately without elimination of the pain and no change of the neurological defects. The complaints increased to an extent that the patient was unable to drive a car, climb stairs or walk a longer distance. In 2008, when he was examined by the rheumatologist and internal medicine specialist, Prof. Dr. Ursula Gresser, in the Praxisklinik Sauerlach, the diagnosis of a traumatic abdominal wall hernia and isolated nerve compression syndrome was made. Prof. Gresser referred the patient to my hernia centre for surgical treatment. The intraoperative findings and histological examination of tissue were consistent with this diagnosis. The difficult meticulous repair of the 14 years old massive defects of the several layers of the abdominal wall and compression of nerves, when crossing these layers, has been made possible in a time demanding open approach with special care for the viable tissue and anatomy. Immediately after the operation the patient had no longer pain in the sacral spine, with a massive decline of pain level in the remaining areas. Without any further pain medication the patient is now able to climb stairs, walk longer distances and drive his car. CONCLUSION: Patients suffering from pain and neurological alterations in the lower abdomen, groins and legs, with or without known trauma, may have a traumatic abdominal wall hernia and nerve compression syndrome. Before planning extensive orthopaedic operations in spine and hip, it is rewarding to exclude other causes, e.g., Sportsman hernia, traumatic hernia or occult hernia. A treatment of the hernia is absolutely necessary to avoid loss of quality of life for the patient and further detrimental development to the patient, e.g., destruction of the head of the femur, deterioration of the respiratory activity and lordosis of the spine. One should not get distracted by evident fractures in the spine to look for other causes of pain.

Inguinal hernia vs. arthritis of the hip in sporting adolescents--case report and review of the literature.

UNLABELLED: Chronic pain in the hip, groin or thigh can be caused by a wide spectrum of diseases posing extended diagnostic problems. We describe the case of a 10-years old child with chronic pain in the groin with gait restriction for more than six months without successful classification and treatment. The girl suffered from heavy pain in the groin after a sporting contest which forced her to walk with walking sticks and to avoid climbing stairs. Within six months she was examined by pediatric, orthopedic, pediatric surgery, pediatric orthopedic, radiology, pediatric rheumatology specialists. Working diagnoses were transient synovitis (coxitis fugax), arthritis, streptococcal arthritis, Morbus Perthes, rheumatic fever, rheumatoid arthritis. She was treated with antibiotics and ibuprofen in high dosage. Repeated laboratory tests and imaging studies (ultrasound, x-rays, magnetic resonance imaging) of the hip and pelvis did not support any of these diagnoses. Six months after beginning of the complaints the girl was presented by her mother to our institution. The physical examination showed a sharp localized pain in the groin, just in the region of the inguinal ligament with otherwise free hip movement. There was no visible inguinal hernia. The family history for hernia was positive. After infiltration of the ilioinguinal nerve the girl had a complete long-lasting disappearance of pain and gait disturbance. This led to the diagnosis of inguinal hernia with nerve entrapment. After hernia repair and neurolysis/neurectomy there was a continuous state of disappearance of pain and gait disturbances. CONCLUSION: To avoid such a diagnostic dilemma one should always discuss all possible causes. Non-visible inguinal hernia may be more common in females than previously thought. Nerve entrapment as a cause of groin pain has been well described. The relationship of the start of complaints with sporting activity, a positive family history for inguinal hernia, a lack of signs of inflammation and bone involvement in the laboratory and imaging studies together with a localized pain in the groin, almost immediate long-lasting disappearance of pain after infiltration of the ilioinguinal nerve allowing free motion leads to the diagnosis of inguinal hernia with nerve entrapment. Hernia repair and neurolysis are the adequate treatment avoiding unnecessary radiation.

Low recurrence rate in hernia repair--results in 300 patients with open mesh repair of primary inguinal hernia.

INTRODUCTION: There are about 700,000 open mesh repairs done as day surgery procedure in the United States each year; in Germany in 2003 only about 6% of inguinal repairs were done as day surgery procedure. STUDY GOAL: Prospective evaluation of complications, recurrence, and chronic postoperative pain after primary inguinal hernia repair with Ultrapro mesh in 300 consecutively operated patients in our clinic. MATERIAL AND METHODS: 300 consecutive patients with primary inguinal hernia repair with Ultrapro mesh were prospectively followed-up. All patients had a defect of the posterior floor (Nyhus III). All patients received antibiotic/anti-thrombotic prophylaxis, pre-emptive pain treatment and were operated by the same surgeon according to a modified Lichtenstein technique. Patients were seen at day 1, day 10, 3 and 12 months after the operation and contacted in case they did not show up. RESULTS: Mean age was 51 years (19-86 years), 218 men (mean age 50) and 82 women (mean age 52). There were 170 direct, 28 indirect and 157 direct and indirect hernias (n = 355). All patients had a defect of the posterior floor (Nyhus IIIa and b). In 55 patients we treated a bilateral hernia. There was no intra-operative complication. One patient (0.3%) complained from minor postoperative nausea and vomiting (PONV). One male patient (smoker) (0.3%) developed an inflammatory reaction in the groin incision; in five patients subcutaneous inflammatory tissue granuloma or seroma were treated surgically. There was neither a case of deep venous thrombosis (DVT), nor pulmonary embolus (PE), nor significant surgical site infection. The mean follow-up of the patients was 13 months (range 1-30 months); 98% of the patients were included in the follow-up. There were four recurrences (1.1%) in 355 hernia repairs. There was no case of chronic pain related to the hernia repair nor a mesh-related complication. 14 patients (4.66%), who had complaints several months after the operation, were thoroughly evaluated and diagnosed to have other causes (intervetrebral disc prolapse, neuropathy, adverse event of a hip joint replacement). CONCLUSION: Open mesh inguinal primary hernia repair can be safely performed with excellent success and good cosmetic results in patients in a specialised ambulatory clinic and is therefore an economic alternative for in-hospital treatment. In comparison to the increased risk for serious complications in laparoscopic inguinal hernia repair there was none in this series. Chronic pain can be successfully prevented by surgical technique and pre-emptive analgesic therapy. The recurrence rate, which has been associated with surgical experience, is low. The results of postoperative pain are only comparable when the patients are seen by the surgeon; evaluation by questionnaire is not sufficient.

Treatment procedures for anal fistulous cryptoglandular abscess--how to get the best results.

INTRODUCTION: Up to date anal fistulous cryptoglandular abscess is a subject of controversial scientific discussions and the number of medico legal cases dealing with treatment procedures is growing . In principal, there is a dispute whether it is reasonable to perform a primary fistulotomy at the time of abscess drainage or to wait for a secondary fistulotomy. The purpose of this study was to compare studies focussing on the treatment of anal fistulous abscess with regard to different treatment procedures, their outcome (recurrence, incontinence, follow-up) and factors influencing outcome (primary or recurrent fistulous abscess, comorbidity, exclusion criteria, anaesthesia, microbiology, antibiotics, search for internal opening, classification). METHODS: A Medline search included the terms: fistulous abscess, anal abscess, horseshoe abscess, anorectal sepsis, and perianal infection/abscess. RESULTS: In 63 (1964-2004) studies we found 35 different treatment methods: the most often used procedures were incision and drainage (I+D; n = 35) and incision and drainage and primary fistulotomy (I+D+pF; n = 23). Only in ten studies the treatment has been restricted for primary anal fistulous abscess; the remaining studies investigated primary and recurrent anal fistulous abscess. There was a considerable lack of information on morbidity, microbiology, and exclusion criteria. In only 16/63 studies patients were routinely diagnosed and treated under general anaesthesia. We found nine different classifications of fistulous abscess. There is a wide range of recurrence after different treatment procedures: up to 88% after I+D and 21% after I+D+pF. The incontinence rate after I+D ranged from 0-26%, after I+D+pF 0-52%. However, in many studies there was no information on incontinence available. CONCLUSION: A true comparison of different treatment methods is not available. This is mainly due to either a lack of information on important factors influencing outcome, even unclear definitions in some instances. Recent randomized studies have been criticized for missing information and flaws in the randomization procedure. The choice of treatment, e.g., primary or secondary fistulotomy, depends on the clinical experience of the surgeon on duty, the hospital structure (staff, equipment, and anaesthesia), the patient's history and the local anatomical circumstances. On the basis of up to date knowledge there is no reason to condemn primary or secondary fistulotomy without more clinical studies and without knowing the individual situation.

Laparoscopic procedures as a risk factor of deep venous thrombosis, superficial ascending thrombophlebitis and pulmonary embolism--case report and review of the literature.

UNLABELLED: Since its introduction laparoscopic surgery has been used for many indications, e.g., cholecystolithiasis, hernia, appendicitis, fundoplication, benign large bowel disease and gynaecological disorders. It has been considered as safe and efficient procedure for most patients with only few contraindications, mostly heart-lung disease. When the initial enthusiasm has been replaced by a more critical observation, more complications of laparoscopy or laparoscopic surgery were not only discovered but also reported. In laparoscopic hernia repair there is a tendency for severe complications when compared to open surgery. There is a controversy on possible side-effects of laparoscopic surgery, e.g., thrombosis, and the increased necessity of prophylaxis for thromboembolic events. Recently a growing number of reports on thromboembolic complications in association with laparoscopic surgery were published. Thrombosis may be caused by detrimental effects of pneumoperitoneum on venous flow (increased abdominal pressure and negative Trendelenburg position) and activation of the haemostatic system. Further risk factors may contribute to the risk to develop venous thrombosis. It is well accepted that varicose veins are associated with an increased risk for the thrombosis. However, the association of varicose veins with complications of laparoscopic surgery is unclear. The possible impact of thrombotic complications makes an analysis of the association of varicose veins or a history of deep vein thrombosis on the development of thrombosis after laparoscopic surgery mandatory. Although this is the first report on ascending thrombophlebitis and thrombosis of the sapheno-femoral junction after laparoscopic surgery, the incidence of deep vein thrombosis or superficial thrombophlebitis after laparoscopic surgery or laparoscopy may be much higher according to the pathophysiological changes during and after these procedures. In many patients venous thrombosis may not be recognized or it appears when the patient is already discharged. CONCLUSION: Laparoscopy and laparoscopic procedures may have an increased risk for the development of thrombosis due to increased abdominal pressure and negative Trendelenburg position. Patients with varicose veins and a history of thromboembolism may aggravate laparoscopy associated risks for the development of thromboembolic complications. Superficial thrombophlebitis in the thigh is not a benign disease entity and may lead to deep vein thrombosis (DVT) and pulmonary embolism (PE). Urgent surgical treatment (high ligation) may be warranted together with low-molecular weight heparin (LMWH) and compressions therapy. Patients with varicose veins and a history of venous thrombosis may not be suitable candidates for laparoscopic surgery. Family practitioners may be confronted with this complication more often since patients are discharged earlier from hospital after laparoscopic interventions due to legislative regulations.

Oral antibiotic prophylaxis can influence the inflammatory response in aortic aneurysm repair: results of a randomized clinical study.

The purpose of this prospective, randomized study was to evaluate the effect of oral ofloxacin prophylaxis on endotoxin/cytokine release in aortic aneurysm repair, in 25 patients with infrarenal aortic aneurysm at a University hospital. Outcome parameters included complications after operation; endotoxin and endotoxin neutralizing capacity, IL-6, procalciton and neopterin. All patients had the standard perioperative antibiotic prophylaxis (2 g cefotiam). 12 patients randomly received oral ofloxacin prophylaxis (group 1) the day before the operation (200 mg/2x12h); 13 patients were controls (group 2). Data were analyzed by chi-square analysis, Mann-Whitney and Wilcoxon analysis. Ofloxacin had no effect on the occurrence of complications or on the peripheral endotoxin levels. Ofloxacin-treated patients showed increased endotoxin neutralizing capacity (ENC) 30 min after clamping compared to controls (15.8+/-15 vs 262.8+/-709 p=0.005) and increased IL-6 levels preoperatively and 30 min after clamping. Patients with complications had significantly higher IL-6 levels early during the operation and postoperatively (30 min after clamping: 36.4+/-15.1 vs 18.8+/-11.9 pg/ml p=0.01; 2nd postoperative day: 768+/-688 vs 225+/-322 pg/ml p=0.005). Ofloxacin prophylaxis had no effect on procalcitonin, or neopterin plasma levels. Neither procalcitonin nor neopterin could detect patients with complications IL-6 plasma levels predicted the occurrence of complications in aortic aneurysm repair. Oral ofloxacin prophylaxis may influence the ENC and IL-6 plasma levels but had no effect on complications, endotoxin and other inflammatory mediators.

Re-operation for complicated secondary peritonitis - how to identify patients at risk for persistent sepsis.

INTRODUCTION: There is an ongoing dispute on the benefit of planned relaparotomy for patients with diffuse peritonitis. SETTING: Surgery Department, university hospital. PATIENTS: 145 patients with diffuse peritonitis treated with planned relaparotomy were analysed for APACHE II, MOF- and MODS-score (Goris and Marshall), complications, outcome and clinical/laboratory factors indicating intra-abdominal compartment syndrome (positive endexpiratory pressure (PEEP), central venous pressure (CVP), creatinine, blood urea nitrogen (BUN)) after termination of planned relaparotomy. Statistical analysis of data (mean and standard deviation) was performed using Mann-Whitney, chi-square, ANOVA and multiple regression analysis. RESULTS: The overall mortality was 29.7% and APACHE II score on admission 16.7 +/- 8.3. In 107 patients (mortality 17.8%) closure of the abdomen was achieved at termination of planned relaparotomy, 20 patients (mortality 30%) were treated with mesh closure and in 18 patients (mortality 100%) closure of the abdomen was not feasible. After closure of the abdomen 39 patients showed signs of persistent sepsis. Patients who were explored had a mortality of 37.5% and without re-exploration a mortality of 67%. BUN, PEEP and CVP were significantly different in survivors and non-survivors. Independent predictors of outcome were closure of the abdomen, complications, APACHE II and MOF scores. CONCLUSION: Patients with planned relaparotomy for diffuse peritonitis are not a uniform group and differ in mortality depending on source control and closure of the abdomen. Patients with persistent sepsis after termination of planned relaparotomy may be recognized by clinical and laboratory parameters and benefit from a timely reexploration. The decision when to close the abdomen may not only be based on intraperitoneal findings but also on the existence and level of organ failure.

IgM-enriched immunoglobulin preparation for immunoprophylaxis in cardiac surgery.

OBJECTIVE: Evaluating the effects of prophylactic administration of IgM-enriched immunoglobulins (IVIG) on immunological- and clinical parameters in cardiac surgical patients. PATIENTS AND METHODS: 41 patients were randomized to receive either an IgM-enriched immunoglobulin (Pentaglobin(R)) preparation (1,300 ml immunoglobulin, equivalent to 65 g protein) combined with routine antibiotic prophylaxis (Group A; n = 20, 1 drop-out), or routine antibiotic prophylaxis plus placebo (Group B; n = 20). Patients were comparable with respect to their APACHE II score, comorbidity, coronary risk, operating time, clamp, and ischemic time. Endotoxin and endotoxin neutralizing capacity (ENC) were determined by a kinetic turbidimetric Limulus amebocyte lysate (LAL) assay with internal standardization. Serum levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF)-alpha, soluble TNF-Receptor I (sTNF-R1), and interleukin-10 (IL-10) were determined by ELISA. Data analysis was performed by area under the curve (AUC) calculation and ANOVA for endotoxin neutralizing capacity and by ANOVA for all other cases. RESULTS: All patients survived. Endotoxin plasma levels were generally but not significantly higher in group A than in controls, while the difference in endotoxin neutralizing capacity (ENC) reached significance. IL-6, TNF-alpha, IL-10 and TNF-R1 were not different between both groups, however. There were significantly less patients with signs of inflammation (fever, leukocytosis, hypotension) in group A (group A n = 2; group B n = 9; p<0.05). This was paralleled by a slightly reduced hospitalization period in group A patients compared to group B patients (A:12.05 +/- 3.66 vs. B:13.45 +/- 3.72 days; n.s.). All data are given as mean +/- standard deviation (SD). CONCLUSION: The results of this study support that IgM-enriched IVIG preparation are effective when used prophylactically in patients undergoing procedures with cardiopulmonary bypass. The mechanisms of endotoxin neutralization and the effect of the host immune status on the efficacy of IVIG treatment remain to be elucidated.

Antibiotic therapy in intra-abdominal infections--a review on randomised clinical trials.

There have been 79 randomised antibiotic studies in intra-abdominal infections retrieved. The overall success rate of the studied antibiotics ranges from 70-100%. Unfortunately only about one fourth of the studies have used a disease severity classification, e.g., APACHE II score, despite clear recommendations by the Surgical Infections Society of North America. The mortality rate in the published antibiotic studies is still rather low (approximately 4%) and does not correspond to the average mortality in peritonitis (30-40%). Failure analysis is not uniform and only performed in about 1/5 of retrieved studies. Failure analysis included data on diagnosis, type of operation, pathogen isolated at first operation, susceptibility and persistence of pathogen, re-operation or change of antibiotic regimen, and follow-up (ICU duration, death or survival, hospitalisation). Only one study has performed an analysis of the adequacy of the surgical treatment (source control). The clinical success rate of the antibiotics studied in a larger population is comparable for gentamicin + clindamycin (80%), tobramycin + clindamycin (83%), meropenem (89%), imipenem (85%), aztreonam + clindamycin (89%), cefoxitin (88%), cefotetan (92%), moxalactam (83%), cefotaxime + metronidazole (87%), ampicillin/sulbactam (87%). Piperacillin/tazobactam has in most studies a success rate of approximately 90%. The aggregated data on adverse events and clinical failure rate do not show a major advantage for any of these antibiotics. It is striking that the adverse event rate reported for ticarcillin/clavulanic acid is low when compared to all other antibiotics, which is in contrast to severe adverse events reported for clavulanic acid. The data of quinolone studies in intra-abdominal infections do not yet allow a recommendation, even when it is acknowledged that two studies were performed with good results and a good study plan. In conclusion, the comparability of antibiotic studies in intra-abdominal infections is limited due to a lack of disease severity stratification and a relatively small study population for most antibiotics. The clinical success rate of the best-studied antibiotics is similar and the choice which antibiotic is used depends on the expected pathogens and the resistance rate in a clinical setting.

Paradigm change in 30 years peritonitis treatment -- a review on source control.

Peritonitis remains a hot spot for surgeons despite advancements in surgical technique and intensive care treatment. There is an ongoing interest to improve the survival rate by analyzing the pathogenesis and pathophysiology of this threatening disease. - The significance of source control, e.g., eradication of a focus of infection, elimination of microbial contamination and restoration of local environment, is well recognized since the beginning of the last century. Recently the term "source control" has gained new interest with regard to guidelines for clinical studies. It appears that despite stratification in most clinical peritonitis studies there is still a lack of comparability of those studies with regard to source control. A medline search on peritonitis and source control was performed and 90 studies were evaluated for information on source control evaluation. In summary, there is no uniform definition of source control available. Most studies in peritonitis treatment are according to evidence based medicine level 3-5 evidence. Lack of hard scientific evidence how to measure the success of source control had to be substituted by surgical experience. Re-operation or relaparotomy may be considered as acknowledgment that source control failed. Controversy exists about primary anastomosis in the inflammed peritoneum. Despite all efforts and more patients enrolled in studies to improve surgical treatment of peritonitis in thirty years it is obvious that the mortality rate has decreased only marginally from 40% to 30%. Commonly accepted principles for source control documentation and evaluation should be established and confirmed in multi-center studies before further studies with new compounds are started.

Antibiotic induced endotoxin release and clinical sepsis: a review.

Sepsis and peritonitis have not lost much of their danger for patients. The mortality rate in peritonitis has only marginally decreased during the last 30 years despite aggressive surgical and sophisticated intensive care treatment. In intra-abdominal infection and peritonitis source control remains the mainstay of treatment, although general principles and denominators of successful source control need to be established. Endotoxin has been recognized as a major player in the pathogenesis of sepsis and its significance in clinical disease has been investigated in clinical studies for more than 20 years. Since the Sixties there is a growing interest in the effect of antibiotics and other compounds on the release of endotoxin. The effect of antibiotics on the release of endotoxin and inflammatory parameters, e.g., cytokines, remains to be clarified despite a growing body of in-vitro studies, animal studies and a few clinical studies. The purpose of this review is to evaluate the evidence of endotoxin release in clinical studies and the effect that antibiotic treatment may have in-vitro, in-vivo and in clinical studies on endotoxin and cytokine release. In-vitro antibiotic-induced endotoxin release may depend on antibiotic class, presence of serum, type of organism, site of antibiotic action and Gram-stain. Endotoxin release may be different in late or early lysis, proportional to the number of killed pathogens. Morphology of bacteria may have an impact on endotoxin release and phagocytosis. Antibiotic-treated animals may show higher endotoxin levels with a higher survival rate than untreated animals. Plasma endotoxin may increase despite decreasing bacteremia. There may be a similar killing rate by different antibiotics but a difference in endotoxin release. Intestinal endotoxin does not necessarily correlate to the level of gram-negative bacteria. However, the alteration of the gut content by pretreatment may be associated with reduced endotoxemia and increased survival. Antibiotic-induced endotoxin release may be different depending on the type of infection, the location of infection, the virulence of strains, Gram-stain, mode of application and dosage of antibiotic. Different antibiotics may induce the release of different forms of endotoxin which may be lethal for sensitized animals. The combination of antibiotics with inhibitors of endotoxin or the pro-inflammatory response may be responsible for increased survival by decrease of endotoxin release. The clinical significance of antibiotic-induced endotoxin release is documented only in a few clinical disorders, e.g., meningitis, urosepsis. The difference in endotoxin release by PBP 2-specific antibiotics, e.g., imipenem, and PBP 3-specific antibiotics, e.g., ceftazidime, may not be visible in each study. Patients with increased multi-organ failure (MOF) scores may profit from treatment with antibiotics known to decrease endotoxin. In conclusion, the clinical significance of antibiotic-induced endotoxin release remains to be clarified. Type of pathogen and its virulence may be more important than recently suggested. gram-positive pathogens were just recently recognized as an important factor for the development of the host response. In case of fever of unknown origin in intensive care patients either failure of treatment, e.g., failure of source control in intra-abdominal infection, or a side effect of antibiotic treatment, e.g., endotoxin release, should be considered as a cause of the fever.

Local and systemic concentrations of pro- and anti-inflammatory cytokines in human wounds.

OBJECTIVE: There is a lack of knowledge on the concentrations of cytokines and growth factors in wound healing. The objective was to characterize the pattern of local-tissue and systemic peri-and postoperative dynamics of cytokines and growth factors in a clinical model of a controlled and comparable operative plastic surgery trauma. DESIGN: Prospective clinical study. - SETTING: A University Department of Surgery. PATIENTS: 28 patients undergoing an elective reduction mammoplasty. MAIN OUTCOME MEASURES: IL-6, IL-8, sTNFR-1 and TGF-beta levels in plasma and wound fluid. RESULTS: Levels of cytokines increased only moderately in plasma. Cytokine levels in wound fluid were several fold higher. IL-6 in the wound fluid peaked at 7 hours after the operation (271 +/- 135.8 pg/ml); IL-8 after 4 hours (11 +/- 9.4 ng/ml); sTNFR-1 at the second postoperative day (11.1 +/- 3.4 ng/ml). TGF-beta decreased at the first (15.2 +/- 8.6 ng/ml) and second (11.7 +/- 5.0 ng/ml) postoperative day. CONCLUSION: Wound cytokine and growth factor levels are markedly higher than the systemic ones indicating a compartmentalization of the immune response. Cytokines peaked at different time points, probably reflecting the influx of inflammatory cells into the wound and the phase of wound healing. Further studies are necessary to clarify the mechanism of cytokine release in normal postoperative wounds before therapeutic use can be developed.

Immunological surrogate parameters in a prognostic model for multi-organ failure and death.

OBJECTIVE: To assess the ability of clinical or biochemical parameters to predict outcome (survival or non-survival; severe or moderate/no complication) using multiple regression analyses. DESIGN: Prospective, descriptive cohort study with no interventions SETTING: 12 surgical intensive care units of university hospitals and large community hospitals; four medical school research laboratories in eight European countries PATIENTS: 128 surgical patients with major intra-abdominal surgery admitted for at least two days to an intensive care unit MAIN OUTCOME MEASURES: Prediction of complications or survival based on analysis of clinical (Multiple Organ Dysfunction Score, Multi-Organ-Failure Score, Acute Physiology and Chronic Health Evaluation II scores) and immunological (plasma levels of endotoxin, endotoxin neutralizing capacity, IL-6, IL-8, cell associated IL-8, Fc-receptor polymorphism, soluble CD-14) parameters, with comparison of predicted and actual outcomes. RESULTS: APACHE II, MODS score, MOF score, platelets, IL-6, IL-8, ENC, cell ass. IL-8 were significantly different between survivors and non-survivors and patients with/without severe complications by univariate analysis. By multivariate analysis only MOF, MODS score, IL-6, platelets, comorbidity predicted complications with a sensitivity of 82% and a specificity of 87%. Multivariate analysis demonstrated that only APACHE II score, plasma IL-8 and complications predicted death (sensitivity 84%; specificity 90%). CONCLUSION: Immunological surrogate parameters may predict complications and death of surgical ICU patients. The use of several parameters may add to increase sensitivity and specificity in a prognostic model.

Pro- and anti-inflammatory cytokine-response in abdominal aortic aneurysm repair: a clinical model of ischemia-reperfusion.

In traumatized and septic patients, excessive cytokine production may lead to organ dysfunction and death. Current understanding of cytokine kinetics with regard to clinical scenarios, however, is still limited by a paucity of studies investigating the cytokine levels in humans with inflammation-reperfusion injury in the absence of infection. Our hypothesis was that endotoxin is introduced into circulation during and after abdominal aortic aneurysm (AAA) repair and is associated with pro- and anti-inflammatory cytokine-response. The purpose of this prospective pilot study in 10 patients who underwent elective AAA repair was to assess organ function and immune response to systemic endotoxemia after the operation by measuring endotoxin, endotoxin neutralizing capacity (ENC), tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-10, and TNF-RI and II. Blood samples were obtained from indwelling catheters or direct venipuncture preoperatively, perioperatively (8 time points) until the second postoperative day. Endotoxin and ENC were determined by a special kinetic Limulus amoebocyte lysate (LAL) assay and TNF-alpha, IL-6, IL-10, and TNF-RI and II by commercial ELISA. Endotoxin levels were significantly elevated after declamping and 90 min after clamping of the aorta (2.3 + .9 pg/mL; 5.4+/-3.6 pg/mL). ENC decreased to the lowest levels at 90 min after clamping. TNF-alpha levels were maximal, but not significantly elevated, 120 min after clamping. IL-6 increased significantly during the operation and reached maximum levels (189.8+/-47 pg/mL) at the first postoperative day. Anti-inflammatory IL-10 and TNF-RI and II were elevated early during the operation. The changes in cytokine levels were associated with mild organ dysfunction. We conclude that AAA repair is associated with endotoxin, proinflammatory, and an almost coincidental anti-inflammatory cytokine release, providing baseline data about what constitutes an appropriate immune response. Such responses to trauma and ischemia-reperfusion need to be further investigated before attempting immunomodulation.

Association of low preoperative serum albumin concentrations and the acute phase response.

OBJECTIVE: To investigate the incidence of a preoperative acute phase response and its association with low albumin concentrations. DESIGN: Prospective open study. SETTING: Teaching hospital, Germany. SUBJECTS: 225 patients who were to undergo major abdominal operations, and who had no acute infections. INTERVENTIONS: Measurements of serum concentrations of albumin, C-reactive protein (CRP), alpha-1 antitrypsin, and interleukin-6 (IL-6). RESULTS: Abnormal concentrations of acute phase proteins (indicating an acute phase response) were detected in 43 of 225 patients (19%). The mean (SD) albumin concentration in these patients (35[5]g/L) was lower than that of patients who did not mount an acute phase response preoperatively (40[5]g/L). High concentrations of CRP (> or =60mg/L) were associated with low albumin concentrations (33[5]g/L); high alpha-1 antitrypsin concentrations (> or =4.0g/L) were associated with low albumin concentrations (34[6]g/L); and high IL-6 concentrations (> or =4pg/ml) were associated with low albumin concentrations (37[6]g/L) compared with a mean(SD) albumin concentration of 40(5)g/L in patients who had no evidence of an acute phase response. CONCLUSION: A metabolic response to disease referred to as an acute phase response may explain low preoperative albumin concentrations. This association interferes with the association of low preoperative albumin concentrations and malnutrition. It is a new aspect of preoperative risk evaluation and may indicate a potential for prevention.

Tumour necrosis factor-alpha and interleukin-10 production in septic patients and the regulatory effect of plasma.

OBJECTIVE: To investigate the capacity of patients' whole blood to produce proinflammatory and antiinflammatory cytokines in severe sepsis and to relate abnormalities to the effect of the patients' plasma on cytokine production in healthy donor blood. DESIGN: Open, prospective clinical study. SETTING: Teaching hospital, Germany. PATIENTS: Ten patients in the surgical intensive care unit with shock and a systemic inflammatory response syndrome (SIRS), a mean APACHE II score of 27, and dysfunction of at least two organ systems at the time of investigation, resulting in 70% mortality. MAIN OUTCOME MEASURES: Tumour necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) concentrations. RESULTS: TNF-alpha and IL-10 production of the whole blood in response to lipopolysaccharide (LPS) was reduced from 2000 pg/ml to 90 pg/ml and from 9163 pg/ml to 622 pg/ml, respectively (p < 0.01). When the plasma of these septic patients was added to the whole blood cells of healthy donors TNF-alpha production decreased by 38% to 1238 pg/ml (p < 0.01) and IL-10 production by 36% to 5857 pg/ml (p = 0.03). CONCLUSION: The effect of plasma from septic patients on the cytokine production in healthy donor blood cells paralleled the decreased production of proinflammatory TNF-alpha and antiinflammatory IL-10 in the whole blood of septic patients. Efforts to modulate cytokine production in septic patients therefore need to take account of the signals from the plasma as well as the functional capacity of the cells.

Infections in intraabdominal surgery. The EURESI Project. European Research Network on Surgical Infections.

The situation of clinical research in Europe must be improved substantially according to statements of scientists, managers and politicians. The analysis of requirements is available; however, there are no indications that the conclusion of the analysis is being converted into actual facts. Government programs, although originally conceived to improve the situation of clinical research, are used to maintain the status quo. The European Research Network on Surgical Infections (EURESI) concept has been developed by scientists and clinicians from European institutions and university hospitals to make the first steps possible in a new cooperation in European research. With regard to the essentials for clinical research, formulated according to a survey among research-oriented pharmaceutical companies, EURESI was successful in the following objectives: 1) competence in clinical research, 2) capacity for clinical studies, 3) internal quality control, 4) special know-how relevant to clinical studies, 5) performance according to a time plan, 6) interdisciplinianism, 7) contract partnership, 8) organization of research meetings. This special addendum includes presentations at the EURESI meeting in Heidelberg/Weinheim with special reference to the requirements for clinical studies in intraabdominal infections to further stimulate contact with the network.