Scope and limitations of antimicrobial therapy of sepsis in surgery.
Wittmann DH. Wittmann-Tylor A.
Department of Surgery, Medical College of Wisconsin, Milwaukee 53226, USA.
OBJECTIVE: The goal of antibiotic therapy for surgical sepsis is to kill bacteria that intermittently or continuously reach the bloodstream from the residue of an operatively treated focus. While sepsis and conditions leading to sepsis compromise the immune system, antibiotics may become a fundamental determinant of the host's defense. No data from sound prospective randomized clinical antibiotic trials dealing with sepsis are available. Therefore we tested the hypothesis that treatment recommendations can be based on pharmacodynamics comparing in vitro activity of commonly used antimicrobials with concentrations sustained in vivo to provide for full coverage for bacteria of concern. RESULTS: The application of strict criteria for antibiotic choice to avoid selection of primary resistant strains reveals that most commonly used antibiotics render insufficient activity to eliminate pathogens that commonly cause surgical sepsis. Antibiotics that sustain in vivo concentration exceeding fourfold the MIC100 (highest minimal inhibitory concentration for all (100%) species tested) of Escherichia coli, for example, are 400 mg ciprofloxacin IV (MIC100 of 1224 strains=0.06 mg/dl, in vivo concentration=1 mg/dl for 12 h), and 1000 mg imipenem/cilastatin (MIC100 of 3142 strains=0.14 mg/dl, in vivo concentration=2 mg/dl for 6 h). The third choice is one of the fourth- or, less convincingly, third-generation cephalosporins. Similar data for most pathogens causing sepsis are provided. First- and second-generation cephalosporins and penicillin beta-lactamase inhibitor combinations generally do not achieve sufficient concentrations to cover the most important pathogens of sepsis. CONCLUSION: Sepsis is defined as a whole body's inflammatory response that is characterized by systemic signs and symptoms secondary to a focal infection. While many antibiotic trials have dealt with a focal infection, no prospective randomized antibiotic trial has dealt with sepsis per se. Antibiotic trials on focal infections generally exclude patients when their focal infection has progressed to sepsis. To circumvent the lack of controlled clinical trials we show that pharmacodynamics may provide sound foundation for antibiotic choice for sepsis.
Management of abdominal sepsis.
Berger D. Buttenschoen K.
Department of General Surgery, University of Ulm, Germany.
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.
Laparoscopic versus conventional colorectal resection: a prospective randomised study of postoperative ileus and early postoperative feeding.
Schwenk W. Bohm B. Haase O. Junghans T. Muller JM.
Department of Surgery, Medical Faculty of the Humboldt-University at Berlin, Charite, Germany.
BACKGROUND: A shorter duration of postoperative ileus and earlier oral alimentation of patients may be a clinically relevant benefit of laparoscopic compared with conventional colorectal resection. PATIENTS/METHODS: A total of 60 patients were randomised to either laparoscopic (n=30) or conventional (n=30) resection of colorectal tumours. Major endpoints were the postoperative time to the first bowel movement and the time until oral feeding without parenteral alimentation was tolerated. Minor endpoints were the postoperative interval to the first peristalsis and first passage of flatus, the distribution of radio-opaque markers in abdominal radiographs on day 3 and day 5 and the incidence of postoperative vomiting. RESULTS: Age, gender. ASA-classification and type of resection were comparable in the two groups. Peristalsis was first noticed 26+/-9 h after laparoscopic and 38+/-17 h after conventional colorectal resection (P
Cystic tumours of the pancreas: diagnostic accuracy, pathologic observations and surgical consequences.
Siech M. Tripp K. Schmidt-Rohlfing B. Mattfeldt T. Widmaier U. Gansauge F. Gorich J. Beger HG.
Department of General Surgery, University of Ulm, Germany.
BACKGROUND: Cystic neoplasms of the pancreas account for only 1% of primary pancreatic lesions. However, patients with these tumors are diagnosed more frequently. Up to now, nonsurgical management is still the established form of treatment of benign cystic tumours of the pancreas. METHODS: Between 1987 and 1996 we treated 51 patients with serous and mucinous cystadenoma and their malignant counterparts, serous and mucinous cystadenocarcinoma. RESULTS: Eighty-five percent of the patients presented symptoms. Computed tomography and endoscopic cholangiopancreatography (ERCP) were the most sensitive diagnostic techniques; however, in three patients with serous cystadenoma and in one patient with serous cystadenocarcinoma, ERCP findings were completely normal. The tumour was resected in all but one patient. There was no perioperative mortality. After dismissal from the hospital, all patients in whom benign tumours had been resected are still alive; however, the late mortality of mucinous cystadenocarcinoma was 36% after a median follow-up of 6 years. CONCLUSION: Surgical resection is recommended in all cystic tumours, even in serous cystic tumours, because symptoms may develop and malignant transformation to serous cystadenocarcinoma is possible.
Treatment of liver metastases in patients with neuroendocrine tumors.
Frilling A. Rogiers X. Malago M. Liedke OM. Kaun M. Broelsch CE.
Department of Surgery, University Hospital Hamburg, Germany.
BACKGROUND: Hepatic metastases of neuroendocrine tumors demand differentiated therapeutic management due to the unique natural course and hormone secretion of the tumors. AIM: The purpose of the prospective nonrandomized study was to review the institutional experience with surgical treatment of hepatic neuroendocrine metastases. PATIENTS AND METHODS: From September 1992 until March 1996 29 consecutive patients with neuroendocrine tumors have been evaluated for surgical treatment of liver metastases. Of them, 11 (37.9%) fulfilled criteria for surgical treatment of hepatic secondary tumors. Extensive preoperative workup was carried out. Patients were divided in groups for curative or palliative resection. Liver transplantation was carried out in selected patients with disseminated liver metastases. RESULTS: Of 29 patients 4 (13.7%) underwent curative resection and in 3 patients (10.3%) palliative resection was performed. The patients who underwent curative resection are all biochemically and clinically tumor free at a mean postoperative follow-up of 22.3 months. Two patients who underwent palliative resection are alive at 40 and 29 months, respectively. From 12 patients evaluated for liver transplantation 4 were considered as suitable candidates. CONCLUSIONS: Liver resection can be recommended in patients with hepatic metastases of neuroendocrine tumors in terms of potential survival prolongation and palliation. Liver transplantation is generally acceptable treatment in highly selected group of these patients. Long-term results have to be awaited before definitive proof of the beneficial effect of surgical treatment.
Reduced TNFalpha and IL-6 production in patients who mount a preoperative acute phase response.
Haupt W. Zirngibl H. Klein P. Riese J. Hohenberger W.
Department of Surgery, University of Erlangen-Nuremberg, Erlangen, Germany.
BACKGROUND/AIMS: In some patients postoperative infective complications are related to a reduced resistance to the operative trauma and the perioperative microbiological challenge. To investigate preoperative alterations in the immune responses in patients who had mounted an acute-phase response before the operation, we measured the capacity of tumor necrosis factor alpha and interleukin-6 production in whole blood. PATIENTS/METHODS: Serum concentrations of C-reactive protein, alpha1-antitrypsin, albumin, and prealbumin were measured in 89 patients submitted for major abdominal surgery on their admission to hospital. RESULTS: In 23 patients (26%) we found concentrations of at least one, and in 16 patients (18%) of two or more of these variables beyond the reference range. Patients who mounted an acute-phase response released 37% less TNFalpha (1339 vs. 848 pg/ml) and 31% less IL-6 (24293 vs. 16900 pg/ml) when whole blood was stimulated with lipopolysaccharide 0.5 microg/ml. CONCLUSION: Patients who mount an acute-phase response before operation may thus have a downregulated immune response at the level of proinflammatory cytokines. This is likely to alter their resistance to invasive micro-organisms in the perioperative period.
De novo expression of the cell adhesion molecule E-selectin on gastric cancer endothelium.
Mayer B. Spatz H. Funke I. Johnson JP. Schildberg FW.
Department of Surgery, Klinikum Grosshadern, University of Munich, Germany.
BACKGROUND AND AIMS: Angiogenesis and the molecular phenotype of the tumor vasculature determine tumor growth and metastasis. PATIENTS/METHODS: In a series of 58 gastric cancer patients, vascular density and the antigenic profile of endothelial cells in normal, inflamed and malignant gastric tissues were compared using immunohistochemistry. RESULTS: In both benign gastric mucosa and primary gastric cancer vascular density was inflammation-independent. However, increased vascularity in primary tumors was positively associated with a high tumor cell density suggesting tumor-induced angiogenesis (P=0.00001 ). P-selectin was expressed in most of the gastric mucosa samples on a small fraction of vessels and increased in the presence of moderate to strong leukocyte infiltrate. VCAM-1 positive mucosal vessels were rare and showed no association with inflammation. E-selectin and the EN 7/44 antigen defining budding vessels were absent on normal and inflamed endothelium. In contrast, in primary gastric cancer de novo expression of both E-selectin and the EN 7/44 antigen was observed. E-selectin positive vessels were preferentially found in vascular-rich tumor areas (P=0.0043) independently of leukocyte infiltration. Upregulation of VCAM-1 on tumor-associated endothelium was closely related to inflammation (P=0.019), while P-selectin expression resembled that in benign mucosa. Conclusions: Differentially expressed vascular molecules may influence the functional characteristics of extravasating leukocytes and represent new targets in anti-gastric cancer therapy.
Role of HLA antigens in liver transplantation with special reference to cellular immune reactions.
Markus BH. Duquesnoy RJ. Blaheta RA. Scholz M. Encke A.
Department of General Surgery, Johann Wolfgang Goethe University, Frankfurt, Germany.
In previous statistical analyses we have demonstrated the importance of the dualistic effect of HLA on liver transplant survival: HLA compatibility decreases cellular rejection but also increases other immunologically mediated, HLA-restricted mechanisms of allograft injury. More recently these results have been confirmed by other researchers, and several studies have shown higher recurrence rates of infectious diseases such as hepatitis B and C and CMV hepatitis for HLA-compatible liver transplants. Although current practice does not consider HLA in liver transplantation, cellular in vitro studies show a significant role of HLA antigens in clinically relevant phenomena. While increasing the amount of infection-related immune damage, HLA compatibility also decreases the alloproliferative response of the recipient to the donor tissue. Further studies must examine whether non-HLA antigens such as tissue-specific antigens and heat-shock-proteins participate in this process, and how target cells can present different peptides such as soluble HLA antigens or viral proteins to the recipient.