Klaus Buttenschoen

Echinococcus granulosus infection: the challenge of surgical treatment

BackgroundCystic echinococcosis (CE) is a worldwide zoonosis caused by larval stages of the cestode Echinococcus granulosus. Surgery, chemotherapy, and interventional procedures are the therapeutic options. Surgery can cure the patient if the parasite is removed entirely. However, the technical procedures are inconsistent and comprise partial liver resection or opening of the parasitic cyst and removal of the parasite. Laparotomy is the most common approach. In selected cases laparoscopic methods are successful. Retrospective studies outweigh prospective ones by far. However, proper management gives favorable results.MethodsWe critically review the literature and present a brief summary of current surgical strategy and focus on issues relevant for surgeons: diagnosis, indication for medical treatment, indication for surgical treatment, surgical procedures, scolicidal agents, morbidity, mortality, recurrence, perioperative medication, standards.ResultsAll surgical procedures aim at the complete removal of the parasite. Liver resection and pericystectomy are procedures that resect the closed cysts with a fairly wide safety margin. A meta-analysis shows the best results regarding lethality (1.2%), morbidity (11.7%), and recurrence rates (2%) for resective operations. However, most surgeons consider these methods as too radical for a benign disease. Procedures that remove the parasite and keep the pericyst (=cystectomy) are easier to carry out than resective ones. The meta-analysis presented revealed a lethality of 2%, morbidity of 23%, and recurrence rate of 10.4% for these operations. Omentoplasty is the option of choice for the management of the remaining cyst cavity. Despite alternative procedures surgery is the treatment of choice. Supportive measures comprise the use of scolicidal agents and postoperative benzimidazole administration. However, a critical review of the literature disclosed a lack of scientific confirmation of established treatment modalities and procedures. The results of ultrasound imaging were classified and correlated to the developmental phases of CE.ConclusionsCystectomy and omentoplasty for CE should be the standard surgical procedure because it is safe, simple, and effective and meets all criteria of surgical treatment for hydatid disease: entire elimination of the parasite, no intraoperative spillage especially by using a cone, and saving healthy tissue. Pericystectomy should be used for peripherally located liver cysts that are surrounded by parenchyma only partially. Ultrasonic classification of the parasitic lesion should be used as a guideline for therapeutic measures.

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.

Management of abdominal sepsis

Introduction: Today the management of the different forms of peritonitis is generally standardised. The classification of primary and secondary peritonitis is well accepted. From a pathophysiological point of view, postoperative and post-traumatic peritonitis should be considered as independent entities. The bacteriological isolates from the inflamed peritoneal cavity do not correlate with the clinical course, and the occurrence of enterococci and bacteroides may be slightly related to ongoing infectious complications. Classification: Valuable scoring systems mainly rely on systemic signs of the septic disease and seem to better differentiate the prognosis of the disease than more surgically oriented scores do. Although the scoring systems did not allow any clinical decision, they should be used to help better compare patients treated in different institutions. The observation of the minor relevance of bacteriology and the superiority of general sepsis scores agrees with the fact that pre-existing septic organ dysfunction and pre-existing comorbidity are the main determinants of mortality. Treatment: Surgical therapy focuses on the control of the source of infection because it has been clearly shown that, without resolving the source of infection, the prognosis remains poor. Adjuvant surgical measures aim at the further reduction of the bacterial load in the peritoneal cavity. Planned relaparotomy, relaparotomy on demand, and continuous closed peritoneal lavage are used. Results: Clinical results proved these methods to be equally effective although pathophysiological considerations favour closed peritoneal lavage. Conclusion: Summarising the available data, we need a more sophisticated understanding of the pathophysiology of the peritonitis, and well-designed clinical studies are necessary to define the optimal surgical treatment modalities.

Endotoxemia and specific antibody behavior against different endotoxins following multiple injuries

The aim of this study was to establish the incidence of endotoxemia and the influence of endotoxin on specific antibody response after multiple injury. Blood samples were collected from 39 patients (median Injury Severity Score: 20.5) at 0-3 and 6-12 hours, and 1, 3, 5, and 10 days after admission. The endotoxin plasma levels were high at the first time point (mean = 0.421 endotoxin units/mL) and decreased in the later course. Total immunoglobulin levels of IgM, IgG, or IgA were low and increased throughout the observation period. Specific antibodies of the IgM class against two lipid A and four lipopolysaccharide preparations increased transiently but significantly on day 3 and/or day 5. No changes of specific antibody content against endotoxin or lipid A was seen in the IgG or IgA class. The specific antibody content of the different classes against alpha-hemolysin of Staphylococcus aureus did not differ during 10 days after trauma. The specific antibodies of the IgM class reacted with all lipid A and LPS lipopolysaccharide preparations demonstrating cross-reactivity. These results suggest that endotoxin may be a specific stimulator of IgM antiendotoxin antibody secretion following trauma.

Endotoxin and antiendotoxin antibodies in patients with acute pancreatitis

OBJECTIVE To elucidate the time course of endotoxaemia and antiendotoxin antibodies in patients with acute pancreatitis. DESIGN Prospective clinical study. SETTING University hospital, Germany. SUBJECTS 25 patients with oedematous (n = 9) or necrotising (n = 16) pancreatitis, and 20 healthy controls. MAIN OUTCOME MEASURES Concentrations of endotoxin and immunoglobulins (classes G, M, and A) directed at two lipid A molecules, four lipopolysaccharides, and alpha-haemolysin of Staphylococcus aureus measurements in plasma during a 12 day period. RESULTS There were no differences in the degree of endotoxaemia between patients with oedematous and necrotising pancreatitis on admission. However, from the day after admission and throughout the observation period patients with necrotising pancreatitis had significantly higher concentrations of endotoxin than those with oedematous pancreatitis. Concentrations of IgM specific for endotoxin peaked at day 4, and then decreased in patients with oedematous pancreatitis while remaining high for those with necrotising pancreatitis. There was only a slight increase in IgA specific for endotoxin, and IgG and immunoglobulins to gamma-haemolysin remained steady throughout the observation period. There was strong cross-reactivity (r > 0.7) between IgM specific for endotoxin (70%), but this was less with IgA (52%), and IgG (20%). CONCLUSIONS Necrotising pancreatitis is accompanied by persistent endotoxaemia with an extended rise in antiendotoxin antibodies. Patients with oedematous pancreatitis have a transient endotoxaemia with a temporary increase of Ig specific for endotoxin. Endotoxin stimulates the synthesis of specific antibodies (IgM) despite general immunosuppression.

Translocation of endotoxin and acute-phase proteins in malleolar fractures

BACKGROUND AND OBJECTIVE Translocation of endotoxins was demonstrated for multiple injury but not for minor trauma such as isolated malleolar fractures. Major trauma leads to substantial changes in the plasma concentration of acute-phase proteins. However, isolated malleolar fractures are minor trauma. The objective of this study was to elucidate the kinetics of endotoxemia and the ability of plasma to inactivate endotoxin of patients operated on malleolar fractures and to demonstrate the early time course of the acute-phase proteins C-reactive protein, transferrin, alpha1-acid glycoprotein, haptoglobin, and interleukin-6 and to correlate them with the amount of endotoxemia. METHODS Thirty patients with malleolar fractures were operated on within 6 hours after injury. Blood was collected immediately after admission and regularly up to 96 hours after surgery. RESULTS Preoperative endotoxin plasma levels were increased compared with that of healthy individuals (0.05 +/- 0.017 vs. 0.02 EU/mL). Endotoxemia peaked 0.5 hours after the surgical procedure at 0.096 +/- 0.03 (p < 0.05 vs. healthy) and decreased to almost normal values after 24 hours. The ability of the plasma to inactivate endotoxin was significantly reduced after the surgical procedure compared with normal subjects (recovery, 0.17 +/- 0.028 EU/mL vs. 0.04 +/- 0.01 EU/mL; p < 0.05). Plasma interleukin-6 peaked 0.5 hours postoperatively (114 +/- 11 pg/mL, p < 0.05 vs. healthy), decreasing thereafter. C-Reactive protein peaked at 45 +/- 5 mg/mL (p < 0.05) 48 hours after injury. Transferrin decreased significantly postoperatively (2.41 +/- 0.12 mg/mL vs. pre-OP 2.65 +/- 0.1 mg/mL) and remained on this level for 96 hours. Both, alpha1-acid glycoprotein and haptoglobin increased postoperatively until day 4 (0.78 +/- 0.06 mg/mL to 1.15 +/- 0.08 mg/mL and 1.51 +/- 0.12 mg/mL to 3.24 +/- 0.22 mg/mL). There was no correlation between endotoxemia and the concentrations of the acute-phase proteins and interleukin-6. CONCLUSION Surgery for malleolar fractures is associated with temporary endotoxemia and temporary reduced endotoxin inactivation capacity of the plasma. The injury and the surgical procedure leads to substantial changes in the plasma concentrations of acute-phase proteins. The relation between endotoxemia and acute-phase response is not dose dependent.

Association of endotoxemia and production of antibodies against endotoxins after multiple injuries.

BACKGROUND Endotoxemia after injury has been a controversial issue. Endotoxins stimulate the innate and adaptive immune system. OBJECTIVE To investigate endotoxemia and its effects on the production of antiendotoxin antibodies of cultured mononuclear cells of patients with multiple injuries. METHODS Blood samples of 20 patients with multiple injuries were collected up to 12 days after trauma. The endotoxin concentration was measured in the plasma, and mononuclear cells were isolated and cultured. Specific antibodies against two lipopolysaccharides, one lipid A preparation, and alpha-hemolysin of Staphylococcus aureus were measured in the cell culture supernatant by an enzyme-linked immunosorbent assay. RESULTS Endotoxemia peaked at admission of the patients, decreasing thereafter to almost normal values within 5 days. Isolated mononuclear cells synthesized antibodies against all tested antigens with a peak at or between day 5 and day 7. The increase was significant for immunoglobulin (Ig)A and IgM specific to all endotoxins tested and for IgA specific to alpha-hemolysin. However, there were no significant changes of the concentrations of total IgM, IgA, and IgG. All specific IgG remained unaffected. CONCLUSION Patients with multiple injuries initially have temporary endotoxemia. Endotoxin may be suggested as a stimulator of the synthesis of antiendotoxin antibodies, in particular of the IgA and IgM class in patients with multiple injuries.

Endotoxin translocation in two models of experimental acute pancreatitis

To test the hypothesis that endotoxin is absorbed from the gut into the circulation in rats with experimental acute pancreatitis we studied two different animal models. In the first model necrotizing pancreatitis was induced by the ligation of the disatl bilio‐pancreatic duct while in the second, experimental oedematous acute pancreatitis was induced by subcutaneous injections of caerulein. In both experiments, in the colon of rats with acute pancreatitis endotoxin from Salmonella abortus equi was injected. Endotoxin was detected by immunohistochemistry in peripheral organs with specific antibodies. The endotoxin was found only in rats with both acute pancreatitis and endotoxin injected into the colon and not in the control groups. The distribution of endotoxin in liver at 3 and 5 days was predominantly at hepatocytes level around terminal hepatic venules, while in lung a scattered diffuse pattern at the level of alveolar macrophages was identified. A positive staining was observed after 12 hours in the liver, lung, colon and mesenteric lymph nodes of rats with both caerulein pancreatitis and endotoxin injected into the colon. We conclude that the experimental acute pancreatitis leads to early endotoxin translocation from the gut lumen in the intestinal wall and consequent access of gut‐derived endotoxin to the mesenteric lymph nodes, liver and lung.

Diverticular disease-associated hemorrhage in the elderly

Abstract. 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 patients 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.

Effect of major abdominal surgery on the host immune response to infection.

Purpose of review The present review summarizes key studies on the effects of major abdominal surgery on the host response to infection published during the last 18 months. Recent findings Surgical trauma causes stereotyped systemic proinflammatory and compensatory anti-inflammatory reactions. It is leukocyte reprogramming rather than general immune suppression. The list of recent findings is long. Preoperative infectious challenge was found to increase survival. Obesity is associated with increased production of interleukin-17A in peritonitis. Abdominal surgery alters expression of toll-like receptors (TLRs). The acute phase reaction down-regulates the transcription factor carbohydrate response element binding protein. Myosin light chain kinase activation is a final pathway of acute tight junction regulation of gut barrier and zonula occludens 1 protein is an essential effector. The brain is involved in regulating the immune and gut system. Elimination of lipopolysaccharide is challenging. Th1/Th2 ratio is lowered in patients with postoperative complications. Cholinergic anti-inflammatory pathways can inhibit tissue damage. The new substance PXL01 prevents adhesions. Postoperative infection causes incisional hernias. Hypothermia reduced human leukocyte antigen DR surface expression and delayed tumor necrosis factor clearance. Systems biology identified interferon regulatory factor 3 as the negative regulator of TLR signaling. Protective immunity could contribute defeating surgical infections. Summary Systemic inflammation is the usual response to trauma. All organs seem to be involved and linked up in cybernetic systems aiming at reconstitution of homeostasis. Although knowledge is still fragmentary, it is already difficult to integrate known facts and new technologies are required for information processing. Defining criteria to develop therapeutic strategies requires much more insight into molecular mechanisms and cybernetics of organ systems.