Prolonged methylprednisolone treatment suppresses systemic inflammation in patients with unresolving acute respiratory distress syndrome: evidence for inadequate endogenous glucocorticoid secretion and inflammation-induced immune cell resistance to glucocorticoids. Pharmacokinetics and pharmacodynamics of methylprednisolone when administered at 8 AM versus 4 PM Mortality and morbidity in gastro-oesophageal cancer surgery: initial results of ASCOT multicentre prospective cohort study Preoperative administration of methylprednisolone attenuates cytokine-induced respiratory failure after esophageal resection. Transthoracic versus transhiatal esophagectomy: a prospective study of 945 patients. Randomized Study of the Benefits of Preoperative Corticosteroid Administration on the Postoperative Morbidity and Cytokine Response in Patients Undergoing Surgery for Esophageal Cancer
Nuclear factor-kappaB ( NF-kappaB ) and glucocorticoid receptor-alpha ( GR-alpha ) have diametrically opposed functions in regulating inflammation . We investigated whether unresolving acute respiratory distress syndrome ( ARDS ) is associated with systemic inflammation- induced glucocorticoid resistance and whether prolonged methylprednisolone administration accelerates the suppression of systemic inflammatory indices and normalizes the sensitivity of the immune system to glucocorticoids . Patients enrolled into a r and omized trial evaluating prolonged methylprednisolone administration in unresolving ARDS had serial plasma sample s collected before and after r and omization . In the plasma , we measured the concentrations of tumor necrosis factor-alpha ( TNF-alpha ) , interleukins ( IL ) IL-1beta and IL-6 , adrenocorticotropic hormone ( ACTH ) , and cortisol . The ability of patient plasma to influence the NF-kappaB and GR-signal transduction systems of normal peripheral blood leukocytes ( PBL ) was examined . Patients treated with methylprednisolone had progressive and sustained reductions of TNF-alpha , IL-1beta , IL-6 , ACTH , and cortisol concentrations over time . Normal PBL exposed to plasma sample s collected during methylprednisolone exhibited significant progressive increases in all aspects of GR-mediated activity and significant reductions in NF-kappaB DNA-binding and transcription of TNF-alpha and IL-1beta . These findings provide support for the presence of endogenous glucocorticoid inadequacy in the control of inflammation and systemic inflammation-induced peripheral glucocorticoid resistance in ARDS . Prolonged methylprednisolone administration accelerated the resolution of both systemic inflammation and peripheral acquired glucocorticoid resistance in ARDS The temporal variations in the pharmacokinetics and pharmacodynamics of methylprednisolone at 8 AM versus 4 PM were investigated in six healthy male volunteers . Subjects completed three phases : no drug administration , 20 mg intravenous methylprednisolone at 8 AM , and the same dose at 4 PM . Methylprednisolone clearance was 28 % greater in the afternoon . The suppressive effects of methylprednisolone on basophils ( measured as whole blood histamine ) , helper T lymphocytes , and cortisol concentrations , assessed by the ratio of the area under the curve ( AUC ) after methylprednisolone to the baseline AUC , were not different between the phases . The 50 % inhibitory concentration values for methylprednisolone derived from pharmacodynamic models were also similar , indicating no difference in intrinsic responsiveness . However , cortisol concentrations returned to baseline about 4 hours earlier after the 4 PM compared with the 8 AM dose because of the enhanced afternoon methylprednisolone clearance . These findings are in agreement with other studies that suggest adequate clinical effects and less disturbance of cortisol circadian behavior when methylprednisolone is administered as a single dose in the morning Abstract Objective To evaluate the effect of comorbidity and other risk factors on postoperative mortality and morbidity in patients undergoing major oesophageal and gastric surgery .  Design Multicentre cohort study with data on postoperative mortality and morbidity in hospital . Data source and methods The ASCOT prospect i ve data base , comprising 2087 patients with newly diagnosed oesophageal and gastric cancer in 24 hospitals in Engl and and Wales between 1 January 1999 and 31 December 2002 .  Multivariate logistic regression analysis was used to model the risk of death and postoperative complications . Results 955 patients underwent oesophagectomy or gastrectomy .  Of these , 253 ( 27 % ) were grade d ASA III or IV , and 187 ( 20 % ) had a high physiological POSSUM score ( ≥ 20 ) . Operative mortality was 12 % ( 111/955 ) . Physiological POSSUM score , surgeon 's assessment , type of operation , hospital case volume , and tumour stage independently predicted operative mortality . Medical complications were associated with higher physiological POSSUM scores and ASA grade , oesophagectomy or total gastrectomy , thoracotomy , and radical nodal dissection . Stage and additional organ resection predicted surgical ( technical ) complications . Conclusions Many patients undergoing surgery for gastro-oesophageal cancer have major comorbid disease , which strongly influences their risk of postoperative death . Technical complications do not seem to be influenced by preoperative factors but reflect the extent of surgery and perhaps surgical judgment . Detailed prospect i ve multicentre cooperative audit , with appropriate risk adjustment , is fundamental in the evaluation of cancer care and must be properly re source Proinflammatory cytokines have been implicated in mediating respiratory failure associated with major surgery . We investigated the effect of giving glucocorticoids preoperatively for the prophylaxis of surgical stress and the association of cytokine levels , such as interleukin-6 ( IL-6 ) and interleukin-8 ( IL-8 ) , with oxygenation after esophagectomy . We studied 17 patients who underwent subtotal esophagectomy . Seven patients ( steroid group ) were chosen at r and om to be given methylprednisolone ( 10 mg/kg ) and 10 patients ( control group ) to be given saline intravenously before operation . Plasma and bronchoalveolar lavage fluid ( BALF ) IL-8 levels in the control group were significantly higher than those in the steroid group . In both groups , plasma IL-6 levels were significantly higher than those in BALF , but in contrast , BALF IL-8 levels were significantly higher than plasma levels of IL-8 postoperatively . The PaO(2)/FiO(2 ) ratio was significantly reduced in the control group . The PaO(2)/FiO(2 ) ratio of the control group had significantly lower values than that of the steroid group . There was significant correlation between BALF IL-8 levels and the PaO(2)/FiO(2 ) ratio postoperatively . We conclude that preoperative administration of methylprednisolone may attenuate postoperative reduction of arterial oxygen saturation by suppressing the release of cytokines OBJECTIVE Debate continues as to whether transhiatal esophagectomy results in lower morbidity and mortality than transthoracic esophagectomy . Most data addressing this issue are derived from single-institution studies . To investigate this question from a nationwide multicenter perspective , we used the Veterans Administration National Surgical Quality Improvement Program to prospect ively analyze risk factors for morbidity and mortality in patients undergoing transthoracic esophagectomy or transhiatal esophagectomy from 1991 to 2000 . METHODS Univariate and multivariate analyses were performed on 945 patients ( mean age , 63 + /- 10 years ) . There were 562 transthoracic esophagectomies and 383 transhiatal esophagectomies in 105 hospitals , with complete 30-day outcomes recorded . RESULTS There were no differences in recorded preoperative variables between the groups that might bias any comparisons . Overall mortality was 10.0 % ( 56/562 ) for transthoracic esophagectomy and 9.9 % ( 38/383 ) for transhiatal esophagectomy ( P = .983 ) . Morbidity occurred in 47 % ( 266/562 ) of patients after transthoracic esophagectomy and in 49 % ( 188/383 ) of patients after transhiatal esophagectomy ( P = .596 ) . Risk factors for mortality common to both groups included a serum albumin value of less than 3.5 g/dL , age greater than 65 years , and blood transfusion of greater than 4 units ( P < .05 ) . When comparing transthoracic esophagectomy with transhiatal esophagectomy , there was no difference in the incidence of respiratory failure , renal failure , bleeding , infection , sepsis , anastomotic complications , or mediastinitis . Wound dehiscence occurred in 5 % ( 18/383 ) of patients undergoing transhiatal esophagectomy and only 2 % ( 12/562 ) of patients undergoing transthoracic esophagectomy ( P = .036 ) . CONCLUSIONS These data demonstrate no significant differences in preoperative variables and postoperative mortality or morbidity between transthoracic esophagectomy and transhiatal esophagectomy on the basis of a 10-year , prospect i ve , multi-institutional , nationwide study Objective To investigate whether preoperative corticosteroid administration plays a role in attenuating postoperative morbidity . Summary Background Data There is as yet no consensus on the beneficial effects of steroids in alleviating surgical stress . Methods A total of 66 patients undergoing surgery for thoracic esophageal cancer were r and omly categorized preoperatively into two groups of 33 patients each . One group was administered an intravenous infusion of methylprednisolone ( 10 mg/kg body weight ) 30 minutes before the surgery ( MP group ) , while the other group received a placebo infusion ( control group ) . The primary endpoint was organ system failure during the first 7 days after surgery . Comparisons of surgery-related complications , cytokine responses , and blood counts were also made between the two groups . Results The percentage of patients in the MP group who had one or more organ system failures was 33 % , significantly lower than the corresponding percentage of 61 % in the control group . The surgery-related complication rate and long-term survival rate were similar in the two groups . The peak plasma levels of interleukin (IL)-1 receptor antagonist , IL-6 , and IL-8 were significantly lower in the MP group than in the control group . Changes in the plasma levels of IL-10 were significantly larger in the MP group . No significant differences in the circulating lymphocyte and neutrophil counts were observed between the groups . Conclusions The results suggest that prophylactic administration of corticosteroids is associated with a decrease in postoperative morbidity in patients undergoing invasive surgery . The laboratory data suggest that corticosteroids may attenuate surgical stress-induced inflammatory responses both directly by suppressing the release of proinflammatory cytokines and via inducing IL-10 synthesis
CONTEXT AND OBJECTIVE Preoperative glucocorticoid administration has been proposed for reducing postoperative morbidity .
This is not widely used before esophageal resection because of incomplete knowledge regarding its effectiveness .
The aim here was to assess the effects of preoperative glucocorticoid administration in adults undergoing esophageal resection for esophageal carcinoma .