Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Journal of Gastrointestinal Surgery
Published in: Journal of Gastrointestinal Surgery 5/2010

01-05-2010 | Original Article

Effect of Preoperative Single-Dose Corticosteroid Administration on Postoperative Morbidity Following Esophagectomy

Authors: Edgard Engelman, Cécile Maeyens

Published in: Journal of Gastrointestinal Surgery | Issue 5/2010

Login to get access

Abstract

Background

Eight clinical trials involving the administration of preoperative i.v. methylprednisolone have been undertaken in order to decrease the considerable inflammatory response to esophageal resection, in an effort to decrease the supposedly associated morbidity and mortality

Method

A meta-analysis was performed for eight clinical end-points. Due to quality problems in seven of the eight included studies, a Bayesian meta-analysis using a skeptical prior derived from the results of the classical analysis was also performed.

Results

The end-points including any organ dysfunction (OR = 0.30), respiratory complication (OR = 0.41), sepsis (OR = 0.37), liver dysfunction (OR = 18), cardiovascular dysfunction (OR = 0.28), and surgical anastomotic leak (OR = 0.42) were significantly decreased by methylprednisolone pretreatment. Following the Bayesian analysis, despite the use of skeptical priors, there is a 95% probability to obtain a relative risk reduction of at least 23% to 54%, depending of the end-point, by methylprednisolone pretreatment.

Conclusion

We are in the presence of a potential benefit that cannot be accepted at face value due to the quality problems of the included studies. But in the presence of a remaining potential benefit after a Bayesian analysis starting from a skeptical prior, the best option would be the planning of a large multicenter prospective randomized study.
Appendix
Available only for authorised users
Literature
1.
Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin 2005;55:74–108.CrossRefPubMed
2.
3.
Leigh Y, Goldacre M, McCulloch P. Surgical specialty, surgical unit volume and mortality after oesophageal cancer surgery. Eur J Surg Oncol 2009;35:820–825.PubMed
4.
Takeda S, Ogawa R, Nakanishi K, Kim C, Miyashita M, Sasajima K, Onda M, Takano T. The effect of preoperative high dose methylprednisolone in attenuating the metabolic response after oesophageal resection. Eur J Surg 1997;163:511–517.PubMed
5.
Matsutani T, Onda M, Sasajima K, Miyashita M. Glucocorticoid attenuates a decrease of antithrombin III following major surgery. J Surg Res 1998;79:158–163.CrossRefPubMed
6.
Shimada H, Ochiai T, Okazumi S, Matsubara H, Nabeya Y, Miyazawa Y, Arima M, Funami Y, Hayashi H, Takeda A, Gunji Y, Suzuki T, Kobayashi S. Clinical benefits of steroid therapy on surgical stress in patients with esophageal cancer. Surgery 2000;128:791–798.CrossRefPubMed
7.
Sato N, Koeda K, Ikeda K, Kimura Y, Aoki K, Iwaya T, Akiyama Y, Ishida K, Saito K, Endo S. Randomized study of the benefits of preoperative corticosteroid administration on the postoperative morbidity and cytokine response in patients undergoing surgery for esophageal cancer. Ann Surg 2002;236:184–190.CrossRefPubMed
8.
Takeda S, Kim C, Ikezaki H, Nakanishi K, Sakamoto A, Okawa K, Miyashita M, Sasajima K, Tajiri T, Tanaka K, Ogawa R. Preoperative administration of methylprednisolone attenuates cytokine-induced respiratory failure after esophageal resection. J Nippon Med Sch 2003;70:16–20.CrossRefPubMed
9.
Yano M, Taniguchi M, Tsujinaka T, Fujiwara Y, Yasuda T, Shiozaki H, Monden M. Is preoperative methylprednisolone beneficial for patients undergoing esophagectomy? Hepatogastroenterology 2005;52:481–485.PubMed
10.
Tsukada K, Miyazaki T, Katoh H, Masuda N, Fukuchi M, Manda R, Fukai Y, Nakajima M, Sohda M, Kimura H, Kuwano H. Effect of perioperative steroid therapy on the postoperative course of patients with oesophageal cancer. Dig Liver Dis 2006;38:240–244.CrossRefPubMed
11.
Sayama J, Shineha R, Yokota K, Hirayama K, Higuchi N, Ohe H, Nakano T, Miyata G, Sugawara K, Ueda H, Nishihira T, Mori S. Control of the excessive reaction after surgery for esophageal carcinoma with preoperative administration of the cortico-steroids. Jpn J Gastroenterol 1994;27:841–848.
12.
Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, McQuay HJ. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 1996;17:1–12.CrossRefPubMed
13.
Mattews RAJ. Methods for assessing the credibility of clinical trial outcomes. Drug Inf J 2001;35:1469–1478.
14.
Spiegelhalter DJ, Abrams KR, Myles JP. An overview of the Bayesian approach. In Spiegelhalter DJ, Abrams KR, Myles JP, ed. Bayesian Approaches to Clinical Trials and Health-Care Evaluation. Chichester: John Wiley & Sons, Ltd, 2004, pp 49–120.
15.
Engelman E, Salengros JC, Barvais L. How much does pharmacologic prophylaxis reduce postoperative vomiting in children? Calculation of prophylaxis effectiveness and expected incidence of vomiting under treatment using Bayesian meta-analysis. Anesthesiology 2008;109:1023–1035.CrossRefPubMed
16.
Engelman E, Salengros JC. IONSYS™ versus morphine PCA: analysis of the current literature using a Bayesian approach. Acute Pain 2008;10:83–91.CrossRef
17.
Kehlet H. Glucocorticoids for peri-operative analgesia: how far are we from general recommendations? Acta Anaesthesiol Scand 2007;51:1133–1135.PubMedCrossRef
18.
Gan TJ, Meyer TA, Apfel CC, Chung F, Davis PJ, Habib AS, Hooper VD, Kovac AL, Kranke P, Myles P, Philip BK, Samsa G, Sessler DI, Temo J, Tramèr MR, Vander Kolk C, Watcha M: Society for ambulatory anesthesia guidelines for the management of postoperative nausea and vomiting. Anesth Analg 2007;105:1615–1628.CrossRefPubMed
19.
Rhen T, Cidlowski HA. Antiinflammatory action of glucocorticoids—new mechanisms for old drugs. N Engl J Med 2005;353:1711–1723.CrossRefPubMed
20.
Wilmore DW. Metabolic response to severe surgical illness: overview. World J Surg 2000;24:705–711.CrossRefPubMed
21.
22.
Holte K, Kehlet H. Perioperative single-dose glucocorticoid administration: pathophysiologic effects and clinical implications. J Am Coll Surg 2002;195:694–712.CrossRefPubMed
23.
Vignali A, Di Palo S, Orsenigo E, Ghirardelli L, Radaelli G, Staudacher C. Effect of prednisolone on local and systemic response in laparoscopic vs. open colon surgery: a randomized, double-blind, placebo-controlled trial. Dis Colon Rectum 2009;52:1080–1088.PubMed
24.
Bailey SH, Bull DA, Harpole DH, Rentz JJ, Neumayer LA, Pappas TN, Daley J, Henderson WG, Krasnicka B, Khuri SF. Outcomes after esophagectomy: a ten-year prospective cohort. Ann Thorac Surg 2003;75:217–222.CrossRefPubMed
25.
Morita M, Yoshida R, Ikeda K, Egashira A, Oki E, Sadanaga N, Kakeji Y, Yamanaka T, Maehara Y. Advances in esophageal cancer surgery in Japan: an analysis of 1000 consecutive patients treated at a single institute. Surgery 2008;143:499–508.CrossRefPubMed
26.
Nagelschmidt M, Fu ZX, Saad S, Dimmeler S, Neugebauer E. Preoperative high dose methylprednisolone improves patients outcome after abdominal surgery. Eur J Surg 1999;165:971–978.CrossRefPubMed
27.
Bigler D, Jonsson T, Olsen J, Brenoe J, Sander-Jensen K. The effect of preoperative methylprednisolone on pulmonary function and pain after lung operations. J Thorac Cardiovasc Surg 1996;112:142–145.CrossRefPubMed
28.
Fecht DC, Magovern GJ, Park SB, Merkow LP, Dixon CM, Dosios T, Pardo M. Benficial effects of methylprednisolone in patienst on cardiopulmonary bypass. Circ Shock 1978;5:415–422.PubMed
29.
Zotti GC, Salzano de Luna F, Caiazza A, Santaniello W, Micheletti G, Bruno A, Casadei CL. Prevention of pulmonary complications by 6-methylprednisolone in major abdominal surgery. Ital Surg Sci 1988;18:369–375.
30.
Law S. Esophagectomy without mortality: what can surgeons do? J Gastrointest Surg 2009; September Epub ahead of print.
31.
Orringer MB, Marshall B, Chang AC, Lee J, Pickens A, Lau CL. Two thousand transhiatal esophagectomies. Changing trends, lessons learned. Ann Surg 2007;246:363–374.CrossRefPubMed
32.
Wright CD, Kucharczuk JC, O’Brien SM, Grab JD, Allen MS. Predictors of major morbidity and mortality after esophagectomy for esophageal cancer: a Society of Thoracic Surgeons General Thoracic Surgery Database risk adjustment model. J Thorac Cardiovasc Surg 2009;137:587–596.CrossRefPubMed
33.
Rizk NP, Bach PB, Schrag D, Bains MS, Turnbull AD, Karpeh M, Brennan MF, Rusch VW. The impact of complications on outcomes after ressection for oesophageal and gastroesophageal junction carcinoma. J Am Coll Surg 2004;198:42–50.CrossRefPubMed
34.
Dunst CM, Swantröm LL. Minimally invasive esophagectomy. J Gastrintest Surg 2010; Sep 30. [Epub ahead of print].
35.
Kingham TP, Pachter HL. Colonic anastomotic leak: risk factors, diagnosis, and treatment. J Am Coll Surg 2009;208:269–278.CrossRefPubMed
36.
Konishi T, Watanabe T, Kishimoto J, Nagawa H. Risk factors for anastomotic leakage after surgery for colorectal cancer: results of prospective surveillance. J Am Coll Surg 2006;202:439–444.CrossRefPubMed
37.
Schultze S, Andersen J, Overgaard H, Norgaard P, Nielsen HJ, Aasen A, Gottrup F, Kehlet H. Effect of prednisolone on the systemic response and wound healing after colonic surgery. Arch Surg 1997;132:129–135.
38.
Kirdak T, Yilmazlar A, Cavun S, Ercan I, Yilmazlar T. Does single, low-dose preoperative dexamethasone improve outcomes after colorectal surgery based on an enhanced recovery protocol? Double-blind, randomized clinical trial. Am Surg 2008:74:106–167.
39.
Shimada M, Saitoh A, Kano T, Takenaka K, Sugimachi K. The effect of a perioperative steroid pulse on surgical stress in hepatic resection. Int Surg 1996;81:49–51.PubMed
40.
Yamashita Y, Shimada M, Hamatsu T, Rikimaru T, Tanaka S, Shirabe K, Sugimachi K. Effects of preoperative steroid administration on surgical stress in hepatic resection. Arch Surg 2001;136:328–333.CrossRefPubMed
41.
Muratore A, Ribero D, Ferrero A, Bergero R, Capussotti L. Prospective randomized study of steroids in the prevention of ischaemic injury during hepatic resection with pedicle clamping. Br J Surg 2003;90:17–22.CrossRefPubMed
42.
Aldrighetti L, Pulitano C, Arru M, Finazzi R, Catena M, Soldini L, Comotti L, Ferla G. Impact of preoperative steroids administration on ischemia-reperfusion injury and systemic responses in liver surgery: a prospective randomized study. Liver Transpl 2006;12:941–949.CrossRefPubMed
43.
Schmidt SC, Hamann S, Langrehr JM, Höflich C, Mittler J, Jacob D, Neuhaus P. Preoperative high-dose steroid administration attenuates the surgical stress response following liver resection: results of a prospective randomized study. J Hepatobiliary Pancreat Surg 2007;14:484–492.CrossRefPubMed
44.
Thornton FJ, Barbul A. Healing in the gastrointestinal tract. Surg Clin North Am 1997;77:549–573.CrossRefPubMed
45.
Kovacs T, Koves I, Orosz Z, Nemeth T, Pandi E, Kralovanszky J. Healing of esophageal anastomoses performed with the biofragmentable anastomosis ring versus the end-to-end anastomosis stapler: comparative experimental study in dogs. World J Surg 2003;27:464–472.CrossRef
46.
Jiborn H, Ahonen J, Zederfeldt B. Healing of experimental colonic anastomoses. IV. Effect of suture technique on collagen metabolism in the colonic wall. Am J Surg 1980;139:406–413.CrossRefPubMed
47.
Fedakar-Sebyucel M, Bingol-Kologlu M, Vargun R, Akbay C, Sarac FN, Renda N, Hasirci N, Gollu G, Dindar H. The effects of local and sustained release of local and sustained release of fibroblast growth factor on wound healing in esophageal anastomoses. J Pediatr Surg 2008;43:290–295.CrossRef
48.
Reavis KM. The esophageal anastomosis: how improving blood supply affects leak rate. J Gastrointest Surg 2009;13:1558–1560.CrossRefPubMed
49.
Thrash CR, Cunningham DD. Stimulation of division of density inhibited fibroblasts glucocorticoids. Nature 1973;242:399–401.CrossRefPubMed
50.
Thrash CR, Ho TS, Cunningham DD. Structural features of steroids which initiate proliferation of density-inhibited 3T3 mouse fibroblasts. J Biol Chem 1974;249:6099–6103.PubMed
51.
Armelin HA. Pituitary extracts and steroid hormones in the control of 3T3 cell growth. Proc Nat Acad Sci 1973;70:2702–2706.CrossRefPubMed
52.
Guttridge DC, Lau AL, Cunningham DD. Protease nexin-1, a thrombin inhibitor, is regulated by interleukin-1 and dexamethasone in normal human fibroblasts. J Biol Chem 1993;268:18966–18974.PubMed
53.
Carney DH, Glenn KC, Cunningham DD. Conditions which affect inhibition of animal cell division by trypsin and thrombin. J Cell Physiol 1978;95:13–22.CrossRefPubMed
54.
McNamara CA, Sarembock IJ, Gimple LW, Fenton JW, Coughlin SR, Owens GK. Thrombin stimulates proliferation of cultured rat aortic smooth muscle cells by a proteolytically activated receptor. J Clin Invest 1993;91:94–98.CrossRefPubMed
55.
Ruhmann AG, Berliner DL. Effect of steroids on growth of mouse fibroblasts in vitro. Endocrinology 1965;76:916–927.CrossRefPubMed
56.
57.
Ishii M, Tanaka E, Imaizumi T, Sugio Y, Sekka T, Tanaka M, Yasuda M, Fukuyama N, Shinozaki Y, Hyodo K, Tanioka K, Mochizuki R, Kawai T, Mori H, Makuuchi H. Local VEGF administration enhances healing of colonic anastomoses in a rabbit model. Eur Surg Res 2009;42:249–257.
58.
Enestvedt CK, Hosack L, Winn SR, Diggs BS, Uchida B, O’Rourke RW, Jobe BA. VEGF Gene therapy augments localized angiogenesis and promotes anastomotic wound healing: a pilot study in a critically relevant animal model. J Gastrointet Surg 2008;12:1762–1772.CrossRefPubMed
59.
Suganami E, Takagi H, Ohashi H, Suzuma K, Suzuma I, Oh H, Watanabe D, Ojima T, Suganami T, Fujio Y, Nakao K, Ogawa Y, Yoshimura N: Leptin stimulates ischemia-induced retinal neovascularization: possible role of vascular endothelial growth factor expressed in retinal endothelial cells. Diabetes 2004;53:2443–2448.CrossRefPubMed
60.
Cao R, Brakenhielm E, Wahlestedt C, Thyberg J, Cao Y. Leptin induces vascular permeability and synergistically stimulates angiogenesis with FGF-2 and VEGF. Proc Natl Acad Sci 2001;98:6390–6395.CrossRefPubMed
61.
Bouloumie A, Marumo T, Lafontan M, Busse R: Leptin induces oxidative stress in human endothelial cells. FASEB J 1999;13:1231–1238.PubMed
62.
Tasdelen A, Algin C, Ates E, Kiper H, Inal M, Sahin F: Effect of leptin on healing of colonic anastomoses in rats. Hepatogastroenterology 2004;51:994–997.PubMed
63.
Hacioglu A, Algin C, Pasaoglu O, Pasaoglu E, Kanbak G. Protective effect of leptin against ischemia-reperfusion injury in the rat small intestine. BMC Gastroenterol 2005;5:37.CrossRefPubMed
64.
Rieth N, Jollin L, Le Panse B, Lecoq AM, Arlettaz A, De Ceaurriz J, Collomp K. Effects of short-term corticoid ingestion on food intake and adipokines in healthy recreationally trained men. Eur J Appl Physiol 2009;105:309–313.CrossRefPubMed
65.
Yilmaz Z, Ilcol YO, Golcu E. Serum leptin and ghrelin levels in response to methylprednisolone injection in healthy dogs. Res Vet Sci 2007;82:187–194.CrossRefPubMed
66.
Pedram A, Razandi M, Hu RM, Levin ER. Vasoactive peptides modulate vascular endothelial cell growth factor production and endothelial cell proliferation and invasion. J Biol Chem 1997;272:17097–17103.CrossRefPubMed
67.
Mobidelli L, Orlando C, Maggi CA, Ledda F, Ziche M. Proliferation and migration of endothelial cells is promoted by endothelins via activation of ETB receptors. Am J Physiol 1995;269:H686–695.
68.
NambiS P, Pullen M, Wu HL, Nuthulagantig P, Elshourbagys N, Kumarg C. Dexamethasone down-regulates the expression of endothelin receptors in vascular smooth muscle cells. J Biol Chem 1992;267:19555–19559.
69.
Brogi E, Wu T, Namiki A, Isner JM. Indirect angiogenic cytokines upregulate VEGF and bFGF gene expression in vascular smooth muscle cells whereas hypoxia upregulates VEGF expression only. Circulation 1994;90:649–652.PubMed
70.
Yamamoto T, Kozawa O, Tanabe K, Akamatsu S, Matsuno H, Dohi S, Uematsu T. Involvement of p38 MAP kinase in TGF-β-stimulated VEGF synthesis in aortic smooth muscle cells. J Cell Biochem 2001;82:591–598.CrossRefPubMed
71.
Tanabe K, Tokuda H, Takai S, Matsushima-Nishiwaki R, Hanai Y, Hirade K, Katagiri Y, Dohi S, Kozawa O. Modulation by the steroid/thyroid hormone superfamily of TGF-β-stimulated VEGF release. J Cell Biochem 2006;99:187–195.CrossRefPubMed
72.
Kimble J, Simpson P. The LIN-12/Notch signaling pathway and its regulation. Annu Rev Cell Dev Biol 1997;13:333–361.CrossRefPubMed
73.
Uyttendaele HG, Marazzi G, Wu QY, Sassoon D, Kitajewski J. Notch4/int-3, a mammary proto-oncogene, is an endothelial cell-specific Notch gene. Development 1996;122:2251–2259.PubMed
74.
Wu J, Bresnick EH. Glucocorticoid and growth factor synergism requirement for Notch4 chromatin domain activation. Mol Cell Biol 2007;27:2411–2422.CrossRefPubMed
75.
Leong KG, Hu X, Li L, Noseda M, Larrivée B, Hull C, Hood L, Wong F, Karsan A. Activated Notch4 inhibits angiogenesis: role of β1-Integrin activation. Mol Cell Biol 2002,22:2830–2841.CrossRefPubMed
76.
Velazquez OC, Snyder R, Liu ZJ, Fairman RM, Herlyn M. Fibroblast-dependent differentiation of human microvascular endothelial cells into capillary-like 3-dimensional networks. FASEB J 2002;16:1316–1318.PubMed
77.
Nakatsu MN, Sainson RCA, Aoto JN, Taylor KL, Aitkenhead M, Pérez-del-Pulgar S, Carpenter PM, Hughes CCW. Angiogenic sprouting and capillary lumen formation modeled by human umbilical vein endothelial cells (HUVEC) in fibrin gels: the role of fibroblasts and Angiopoietin-1. Microvasc Res 2003;66:102–112.CrossRefPubMed
78.
Tsopanoglou NE, Maragoudakis ME. Role of thrombin in angiogenesis and tumor progression. Semin Thromb Hemost 2004;30:63–69.CrossRefPubMed
79.
Talas DU, Nayci A, Atis S, Polat A, Comelekoglu U, Bagdatoglu C, Renda N. The effects of corticosteroids on the healing of tracheal anastomoses in a rat model. Pharmacol Res 2002;45:299–304.CrossRefPubMed
80.
Murthy SC, Law S, Whooley BP, Alexandrou A, Chu KM, Wong J. Atrial fibrillation after esophagectomy is a marker for postoperative morbidity and mortality. J Thorac Cardiovasc Surg 2003;126:1162–1167.CrossRefPubMed
81.
Deng MC, Dasch B, Erren M, Möllhoff T, Scheld HH. Impact of left ventricular dysfunction on cytokines, hemodynamics, and outcome in bypass grafting. Ann Thorac Surg 1996;62:184–190.CrossRefPubMed
82.
Hennein HA, Ebba H, Rodriguez JL, Merrick SH, Keith FM, Bronstein MH, Leung JM, Mangano DT, Greenfield LJ, Rankin JS. Relationship of the proinflammatory cytokines to myocardial ischemia and dysfunction after uncomplicated coronary revascularization. J Thorac Cardiovasc Surg 1994;108:626–635.PubMed
83.
Roumen RM, Hendriks T, van der Ven-Jongekrijg J, Nieuwenhuijzen GA, Sauerwein RW, van der Meer JW, Goris RJ. Cytokine patterns in patients after major vascular surgery, hemorrhagic shock, and severe blunt trauma. Relation with subsequent adult respiratory distress syndrome and multiple organ failure. Ann Surg 1993;218:769–776.CrossRefPubMed
Metadata
Title
Effect of Preoperative Single-Dose Corticosteroid Administration on Postoperative Morbidity Following Esophagectomy
Authors
Edgard Engelman
Cécile Maeyens
Publication date
01-05-2010
Publisher
Springer-Verlag
Published in
Journal of Gastrointestinal Surgery / Issue 5/2010
Print ISSN: 1091-255X
Electronic ISSN: 1873-4626
DOI
https://doi.org/10.1007/s11605-010-1168-0

Other articles of this Issue 5/2010

Journal of Gastrointestinal Surgery 5/2010 Go to the issue

Review Article

Congenital Anomalies of the Gastrointestinal Tract Diagnosed in Adulthood—Diagnosis and Management

Original Article

Dose Delivery Estimated by Bremsstrahlung Imaging and Partition Model Correlated with Response Following Intra-arterial Radioembolization with 32P-Glass Microspheres for the Treatment of Hepatocellular Carcinoma

Original Article

Management and Outcome of Gastrointestinal Stromal Tumors of the Duodenum

GI Image

Frey Procedure for Pancreaticopleural Fistula

Original Article

4-Dimensional Intravital Microscopy: A New Model for Studies of Leukocyte Recruitment and Migration in Hepatocellular Cancer in Mice

Original Article

Influence of Body Mass Index on Complications and Oncologic Outcomes Following Hepatectomy for Malignancy