Sind Leukozyten und C-reaktives Protein geeignete Parameter als Frühindikatoren der Anastomoseninsuffizienz nach Ösophagusresektion?[1]

Zusammenfassung

Hintergrund: Anastomoseninsuffizienzen nach Ösophagusresektion stellen eine potenziell lebensbedrohliche Komplikation dar. Durch frühzeitige Diagnostik und Therapie kann die Letalität verringert werden. Ziel dieser Studie war es, die Bedeutung von Standardentzündungsparametern im Serum [Leukozytenzahl, C-reaktives Protein (CRP)] als Indikator für eine Anastomoseninsuffizienz zu untersuchen. Patienten und Methode: Zwischen 1 / 1997 und 12 / 2006 wurden 558 Patienten mit Ösophaguskarzinom mittels Zweihöhleneingriff und intrathorakaler Anastomose operiert. Aus diesem Kollektiv wurden alle Patienten (n = 50, 8.9 %) mit Anastomoseninsuffizienz und 50 Patienten ohne Anastomoseninsuffizienz verglichen. Im früh-postoperativen Verlauf wurden Entzündungsparameter (Leukozyten und CRP) sowie klinische Parameter (Körpertemperatur, kardiale und respiratorische Störungen, Wund- und Dränagesekretion) retrospektiv analysiert. Ergebnisse: Bei Patienten mit Anastomoseninsuffizienz nach Ösophagusresektion konnten signifikant erhöhte Leukozyten- und CRP-Werte im Vergleich zu Patienten ohne Anastomoseninsuffizienz ab dem fünften bzw. zweiten postoperativen Tag nachgewiesen werden. Die schrittweise Regressionsanalyse zeigte eine 80 %-Sensitivität für das Auftreten einer Anastomoseninsuffizienz bei einem Cut-off-Wert von 13,5 mg / dl für das CRP ab dem 2. bzw. 10,5 Gpt / l für Leukozyten ab dem 8. postoperativen Tag. Ferner wiesen Patienten mit Anastomoseninsuffizienz häufiger respiratorische Probleme oder Schmerzen im Abdomen auf. Schlussfolgerung: In der Frühdiagnostik der Anastomoseninsuffizienz nach Ösophagusresektion ist das CRP im Gegensatz zur Bestimmung der Leukozyten im Serum ein zuverlässiger und sensitiver Screening-Parameter, dessen Erhöhung Anlass zu weiterer Diagnostik geben sollte.

Abstract

Background: Anastomotic leaks represent the most common severe postoperative complications after esophagectomy. In this study standard inflammatory laboratory parameters [leukocytes, C-reactive protein (CRP)] were evaluated as indicators for anastomotic leakage after esophagectomy. Patients and Methods: Between 1 / 1997 and 12 / 2006 a total of 558 patients with esophageal cancer underwent an Ivor-Lewis esophagectomy. Among these patients, all those (n = 50, 8.9 %) suffering from an anastomotic leak were matched to 50 patients without anastomotic leakage. Leukocytes, CRP level and clinical parameters (body temperature, cardiac / respiratory problems, wound secretion) were retrospectively analysed at short-term intervals in both groups. Results: Patients with anastomotic leaks showed significant continuously increased CRP levels and leukocyte counts from the second or, respectively, 5^th postoperative day onwards compared to patients without anastomotic leaks. Using a stepwise regression, an 80 % sensitivity for leakage detection has been calculated by a cut-off value for CRP set at 13.5 mg / dL from day 2 onwards or, respectively, for leukocytes at 10.5 Gpt / L from day 8 onwards. Concomitantly, patients with anastomotic leaks suffered significantly more from respiratory problems and abdominal pain. Conclusion: CRP appears to be a reliable and predictable indicator for anastomotic leakage after esophagectomy and should, therefore, be routinely used as a screening marker to provide a reason for extended diagnosis.

Schlüsselwörter

Ösophagusresektion - Anastomoseninsuffizienz - Entzündungsparameter

Key words

esophageal resection - anastomotic leakage - serum parameters

1 Präsentation der Daten auf dem „123. Kongress der Deutschen Gesellschaft für Chirurgie“

Literatur

• 1 Allum W H, Griffin S M, Watson A et al. Guidelines for the management of oesophageal and gastric cancer.  Gut. 2002;  50 1-23
• 2 Berger D, Bolke E, Seidelmann M et al. Time-scale of interleukin-6, myeloid related proteins (MRP), C reactive protein (CRP), and endotoxin plasma levels during the postoperative acute phase reaction.  Shock. 1997;  7 422-426
• 3 Bitkover C Y, Hansson L O, Valen G et al. Effects of cardiac surgery on some clinically used inflammation markers and procalcitonin.  Scand Cardiovasc J. 2000;  34 307-314
• 4 Bogar L, Molnar Z, Tarsoly P et al. Serum procalcitonin level and leukocyte antisedimentation rate as early predictors of respiratory dysfunction after oesophageal tumour resection.  Crit Care. 2006;  10 R110
• 5 Bruce J, Krukowski Z H, Al-Khairy G et al. Systematic review of the definition and measurement of anastomotic leak after gastrointestinal surgery.  Br J Surg. 2001;  88 1157-1168
• 6 Castelli G P, Pognani C, Meisner M et al. Procalcitonin and C-reactive protein during systemic inflammatory response syndrome, sepsis and organ dysfunction.  Crit Care. 2004;  8 R234-R242
• 7 Ferard G, Gaudias J, Bourguignat A et al. C-reactive protein to transthyretin ratio for the early diagnosis and follow-up of postoperative infection.  Clin Chem Lab Med. 2002;  40 1334-1338
• 8 Gaini S, Koldkjaer O G, Pedersen C et al. Procalcitonin, lipopolysaccharide-binding protein, interleukin-6 and C-reactive protein in community-acquired infections and sepsis: a prospective study.  Crit Care. 2006;  10 R 53
• 9 Goel A K, Sinha S, Chattopadhyay T K. Role of gastrografin study in the assessment of anastomotic leaks from cervical oesophagogastric anastomosis.  Aust N Z J Surg. 2005;  65 8-10
• 10 Griffin S M, Lamb P J, Dresner S M et al. Diagnosis and management of a mediastinal leak following radical oesophagectomy.  Br J Surg. 2001;  88 1346-1351
• 11 Griffin S M, Shaw I H, Dresner S M. Early complications after Ivor Lewis subtotal esophagectomy with two-field lymphadenectomy: risk factors and management.  J Am Coll Surg. 2002;  194 285-297
• 12 Huber-Lang M, Henne-Bruns D, Schmitz B et al. Esophageal perforation: principles of diagnosis and surgical management.  Surg Today. 2006;  36 332-340
• 13 Ito S, Sato N, Kojika M et al. Serum procalcitonin levels are elevated in esophageal cancer patients with postoperative infectious complications.  Eur Surg Res. 2005;  37 22-28
• 14 Kofoed K, Andersen O, Kronborg G et al. Use of plasma C-reactive protein, procalcitonin, neutrophils, macrophage migration inhibitory factor, soluble urokinase-type plasminogen activator receptor, and soluble triggering receptor expressed on myeloid cells-1 in combination to diagnose infections: a prospective study.  Crit Care. 2007;  11 R 38
• 15 Kofoed K, Schneider U V, Scheel T et al. Development and validation of a multiplex add-on assay for sepsis biomarkers using xMAP technology.  Clin Chem. 2006;  52 1284-1293
• 16 Lam T C, Fok M, Cheng S W et al. Anastomotic complications after esophagectomy for cancer. A comparison of neck and chest anastomoses.  J Thorac Cardiovasc Surg. 1992;  104 395-400
• 17 Lamb P J, Griffin S M, Chandrashekar M V et al. Prospective study of routine contrast radiology after total gastrectomy.  Br J Surg. 2004;  91 1015-1019
• 18 Lannergard A, Hersio K, Larsson A et al. Evaluation of laboratory markers for the detection of infections in openheart surgery patients.  Scand J Infect Dis. 2003;  35 121-126
• 19 Lerut T, Coosemans W, Decker G et al. Anastomotic complications after esophagectomy.  Dig Surg. 2002;  19 92-98
• 20 Lorentz T, Fok M, Wong J. Anastomotic leakage after resection and bypass for esophageal cancer: lessons learned from the past.  World J Surg. 1989;  13 472-477
• 21 Macrina F, Tritapepe L, Pompei F et al. Procalcitonin is useful whereas Creactive protein is not, to predict complications following coronary artery bypass surgery.  Perfusion. 2005;  20 169-175
• 22 Matthews H R, Mitchell I M, McGuigan J A. Emergency subtotal oesophagectomy.  Br J Surg. 1989;  76 918-920
• 23 Meisner M, Adina H, Schmidt J. Correlation of procalcitonin and C-reactive protein to inflammation, complications, and outcome during the intensive care unit course of multiple-trauma patients.  Crit Care. 2006;  10 R 1
• 24 Mokart D, Leone M, Sannini A et al. Predictive perioperative factors for developing severe sepsis after major surgery.  Br J Anaesth. 2005;  95 776-781
• 25 Molnar Z, Szakmany T, Koszegi T et al. Microalbuminuria and serum procalcitonin levels following oesophagectomy.  Eur J Anaesthesiol. 2000;  17 464-465
• 26 Oberhofer D, Rumenjak V, Lazic J et al. Inflammatory indicators inpatients after surgery of the large intestine.  Acta Med Croatica. 2006;  60 429-433
• 27 Orringer M B, Stirling M C. Esophagectomy for esophageal disruption.  Ann Thorac Surg. 1990;  49 35-42
• 28 Palmes D, Weilinghoff M, Colombo-Benkmann M et al. Effect of pyloric drainage procedures on gastric passage and bile reflux after esophagectomy with gastric conduit reconstruction.  Langenbecks Arch Surg. 2007;  392 135-141
• 29 Povoa P, Almeida E, Moreira P et al. C-reactive protein as an indicator of sepsis.  Intensive Care Med. 1998;  24 1052-1056
• 30 Povoa P, Coelho L, Almeida E et al. C-reactive protein as a marker of infection in critically ill patients.  Clin Microbiol Infect. 2005;  11 101-108
• 31 Rizk N P, Bach P B, Schrag D et al. The impact of complications on outcomes after resection for esophageal and gastroesophageal junction carcinoma.  J Am Coll Surg. 2004;  198 42-50
• 32 Rothenburger M, Markewitz A, Lenz T et al. Detection of acute phase response and infection. The role of procalcitonin and C-reactive protein.  Clin Chem Lab Med. 1999;  37 275-279
• 33 Siewert J R, Stein H J, Bartels H. Anastomotic leaks in the upper gastrointestinal tract.  Chirurg. 2004;  75 1063-1070
• 34 Simon L, Gauvin F, Amre D K et al. Serum procalcitonin and C-reactive protein levels as markers of bacterial infection: a systematic review and meta-analysis.  Clin Infect Dis. 2004;  39 206-217
• 35 Tam P C, Fok M, Wong J. Reexploration for complications after esophagectomy for cancer.  J Thorac Cardiovasc Surg. 1989;  98 1122-1127
• 36 Uzzan B, Cohen R, Nicolas P et al. Procalcitonin as a diagnostic test for sepsis in critically ill adults and after surgery or trauma: a systematic review and meta-analysis.  Crit Care Med. 2006;  34 1996-2003
• 37 Whooley B P, Law S, Alexandrou A et al. Critical appraisal of the significance of intrathoracic anastomotic leakage after esophagectomy for cancer.  Am J Surg. 2001;  181 198-203
• 38 Wu P C, Posner M C. The role of surgery in the management of oesophageal cancer.  Lancet Oncol. 2003;  4 481-488
• 39 Yang M D, Jeng L B, Kao A et al. C-reactive protein and gallium scintigraphy in patients after abdominal surgery.  Hepatogastroenterology. 2003;  50 354-356

1 Präsentation der Daten auf dem „123. Kongress der Deutschen Gesellschaft für Chirurgie“