Comparison of the effects of on-pump versus off-pump coronary artery bypass surgery on serum prostate-specific antigen levels

Authors


Bekir Süha Parlaktas md, Mevlana Sitesi, 2 Blok, Kat 2 No. 5, 60100 Tokat, Turkey. Email: bsuha@mynet.com

Abstract

Aim:  To compare the effects of coronary artery bypass operation with or without extracorporeal circulation on serum total prostate-specific antigen levels.

Methods:  Seventy-six men with a mean age of 57.04 ± 9.27 years (range 44–77 years), who underwent coronary artery bypass surgery were enrolled to the study. In 50 patients (Group I), coronary revascularization was performed using extracorporeal circulation, and in 26 patients (Group II) coronary bypass grafting was performed on the beating heart without using extracorporeal circulation. All the patients had serum total prostate-specific antigen levels measured preoperatively and twice postoperatively in the first and fifth postoperative days. Differences in mean total prostate-specific antigen levels between the two groups in the postoperative period were analysed.

Results:  The mean preoperative total prostate-specific antigen levels in Group I and Group II were 1.28 ± 1.13 ng/mL and 1.11 ± 0.93 ng/mL, respectively, and there was no significant difference in the preoperative total prostate-specific antigen values between the two groups (= 0.519). In Group I, postoperative means were 4.96 ± 6.29 ng/mL and 5.86 ± 9.09 ng/mL in the first and fifth days, respectively (= 0.0001, P = 0.0001). Total prostate-specific antigen means in the same postoperative period for Group II were 2.13 ± 2.72 ng/mL and 2.00 ± 2.20 ng/mL, respectively (= 0.014, P = 0.024). The comparison of total postoperative prostate-specific antigen levels between the groups showed significantly higher elevation in Group I (postoperative day 1: P = 0.013; day 5: P = 0.05).

Conclusions:  Coronary revascularization can cause a statistically significant rise in serum total prostate-specific antigen levels. This rise is more marked in patients undergoing conventional coronary revascularization.

Introduction

Prostate-specific antigen (PSA) is a kallikrein-like serine protease, which is produced by the epithelial cells of the acinar and ductal elements of the prostate gland.1–3 The serum level of PSA is a widely used tumor marker for the diagnosis and follow up of prostate cancer.1,2 It is not specific for prostate cancer and may be elevated in some benign diseases of prostate gland such as benign prostatic hyperplasia, prostatic and urinary system infections, prostatic abscess, and after urologic manipulations such as cystoscopy, prostate biopsy and transurethral resection of prostate gland.2–6 Elevation of serum PSA levels due to prostatic ischemia and/or infarction has been demonstrated in some previous studies.1,3 Pelvic ischemia due to cross clamping of the aorta during coronary artery bypass grafting (CABG), aortic and iliac arterial surgery, hypotensive shock and acute myocardial infarction is presumed to be the reason for prostatic ischemia and/or infarction leading to elevation of serum PSA levels.1–3,7,8

Significant stenosis of the coronary arteries has traditionally been treated with conventional coronary artery bypass (CCAB) which utilizes extracorporeal circulation (ECC),9,10 The flow of blood through ECC circuits induces a generalized inflammatory reaction in the body which has been postulated as the main cause of morbidity and mortality in these patients.9 In order to avoid the deleterious effects of ECC, off-pump or beating-heart coronary artery bypass (OPCAB) has regained popularity in the last few years.11,12 The objective of the present study was to investigate the early postoperative impacts of two different CABG procedures on serum PSA levels.

Methods

Seventy-six men with a mean age of 57.04 ± 9.27 years (range 44–77 years), who underwent CABG in the cardiovascular surgery department between January 2004 and December 2004, were enrolled to this prospective study. The patients were divided into two groups. Those undergoing CCAB surgery constituted Group I and those who underwent coronary revascularization with OPCAB constituted Group II. All of the surgical procedures were performed by the same surgical team. Patients who had a history of malignancy of prostate or any other organ, previous pelvic and inguinal irradiation, open or transurethral surgery for benign prostatic hyperplasia, and patients who had high PSA levels before the operation were excluded from the study. Recent genitourinary tract infection, acute and chronic prostatitis, any prior urological manipulations within 1 month, cardiac operation within the last 3 months and medications affecting PSA levels were among the other exclusion criteria. Comparison of the preoperative data of the patients between the groups are presented in Table 1.

Table 1.  Baseline and preoperative characteristics of the patients
CharacteristicGroup I (n = 50)Group II (n = 26)tχ2P
  1. AF, atrial fibrillation; CHF, congestive heart failure; COPD, chronic obstructive pulmonary disease; CVD, cerebrovascular disease; DM, diabetes mellitus; LVD, left ventricular dysfunction; RF, renal failure; USAP, unstable angina pectoris.

Age (years; mean)56.76 ± 9.5757.58 ± 8.810.3620.718
DM (%)52500.0270.869
COPD (%)58690.9140.339
RF (%) 411.50.2091.582
CVD (%) 8 3.80.655
Preoperative AF (%) 2 7.70.268
USAP (%)3242.30.7930.373
CHF (%)2415.30.7640.382
LVD (%)2615.31.1000.292

Serum specimens of all patients were obtained preoperatively and twice postoperatively for serum total PSA (tPSA) level determination. Preoperative blood was taken in the operation morning (tPSA0), the first postoperative specimen was obtained within 16 to 24 h postoperatively (tPSA1), and the second on the fifth postoperative day (tPSA5). All serum tPSA determinations were performed at the same laboratory with chemiluminescent enzyme immunoassay method which uses a reference range of 0–4 ng/mL (Immulite 2000 PSA; Diagnostic Products Corporation, Los Angeles, CA, USA). A silicone coated, 18-Fr Foley urethral catheter was applied to all patients by the induction of general anaesthesia and taken out within the first 24 h.

Values were presented as arithmetic mean ± SD. Preoperative data of the patients were analysed with χ2-test and Fisher's Exact χ2-tests. The Wilcoxon signed rank test was used for the comparisons of the baseline and postoperative tPSA values within each group (the Levene test was used when the data were not normally distributed). Analysis of means between the groups were performed by t-test for independent samples and Mann–Whitney U-test (the Levene test was used when the data were not normally distributed).

Results

Operative and postoperative data of the patients are presented in Table 2. There was a significant difference between the groups as far as the operative and postoperative findings are concerned (= 0.0001).

Table 2.  Operative and postoperative findings in both groups
 Group IGroup IItP
  • *

    Significant. AF, atrial fibrilation; CVA, cerebrovascular accident; IABP, intra-aortic balloon pulsation; ICU, intensive care unit stay; LOS, length of postoperative hospital stay; MI, myocardial infarction; RF, renal failure.

Operation time (h)1.26 ± 0.211.05 ± 0.213.9740.0001*
Number of grafts 2.81.9
Evolving MI (%) 2.00.0
IABP (%)20.00.0
Hemorrhage (mL)655 ± 240420 ± 2224.1460.0001*
Blood transfusion (units)2.48 ± 1.120.96 ± 1.115.5890.0001*
Postoperative AF (%) 4.07.7
Postoperative CVA (%) 0.00.0
Postoperative RF (%) 2.00.0
Respiratory insufficiency (%) 6.03.8
ICU (days)0.8 ± 0.20.5 ± 0.24.4210.0001*
LOS (days)6.2 ± 1.54.6 ± 1.43.7450.0001*

Total PSA values for both groups are presented in Table 3. Preoperative tPSA values were 1.28 ± 1.13 ng/mL and 1.11 ± 0.93 ng/mL in Group I and II, respectively. There was no statistically significant difference between these values (= 0.519). Evaluation of tPSA values showed a statistically significant rise in the postoperative period in each group. For Group I, P = 0.0001 in day 1 and P = 0.0001 in day 5. For Group II these values were P = 0.014 in day 1, and P = 0.024 in day 5. Both tPSA1 and tPSA5 values were statistically higher in Group I than Group II (Table 3).

Table 3.  Prostate-specific antigen statistics, comparison of preoperative and postoperative prostate-specific antigen means between the groups
 Group IGroup IItzP
  • *

    Significant. Values are mean ± SD. PSA, prostate-specific antigen; PSA0, preoperative PSA; PSA1, postoperative first day PSA; PSA5, postoperative fifth day PSA.

PSA0 (ng/mL)1.28 ± 1.131.11 ± 0.930.6470.519
PSA1 (ng/mL)4.96 ± 6.292.13 ± 2.72−2.4960.013*
PSA5 (ng/mL)5.86 ± 9.092.00 ± 2.20−2.8140.005*

Discussion

Prostate-specific antigen is a well-known marker for adenocarcinoma of the prostate gland and it is released into the extracellular compartment by some physiologic and pathologic disease processes that insult the prostatic parenchyma and disrupt the cellular basement membrane architecture within the prostatic acinar and ductal structures.1,2,4 An interassay variability of 3–8% and daily biological variation of 7–12% in serum PSA has also been reported.7,13 Many conditions may cause elevation of serum PSA levels and therefore specific consideration should be made for these situations when interpreting PSA levels.2,5,13,14 Prostatic ischemia and/or infarction may also cause elevation of PSA and rare previous studies have put forth their results for consideration.1,3,7 Although several factors may contribute to the elevation of PSA levels postoperatively, intraoperative prostatic ischemia which induces prostatic epithelial cell damage leading to a concomitant serum PSA concentration elevation is considered to be the dominant pathophysiologic factor.1,2,7 Coronary artery disease and prostatic neoplasia are among the most common diseases afflicting the aging male population and CABG is one of the most frequently performed surgical procedures for a male population at risk for prostatic disorders.1,3,7,15

Any urologist can reasonably be asked to evaluate a patient in the early postoperative period of CABG operation for acute urinary retention or any other urologic complaints.1 As common sense suggests that, such a man should not be screened for prostate cancer at this point, and nobody would perform a prostate biopsy in a very recent postoperative period after CAB surgery, detection of a raised postoperative serum PSA level may still arise suspicion and may warrant invasive evaluation techniques for prostate cancer screening afterwards.1,3

Together with the surge in interest in minimally invasive cardiac surgery, the number of OPCAB cases has increased markedly in the last decade.9,11 The major advantage of OPCAB is to avoid the non-physiologic effects of the cardiopulmonary circuits and ischemic low flow states as in CCAB.9–12,15,16 Although there are hypotensive periods mostly leading to subclinical organ ischemia during OPCAB, this surgical modality has been shown to cause much lower incidence of ischemia–reperfusion injury, lower postoperative complications of multiple organ dysfunction and reduced postoperative elevations of markers of systemic inflammatory response.10,11,15,16 Eliminating the need for ECC and cardioplegic arrest in OPCAB surgery is thought to decrease the mortality and morbidity especially in high-risk patients.17 Myocardial revascularization with OPCAB decreases the postoperative neurologic, pulmonary, renal complications, lower bleeding and thus transfusion related and infectious complications.16,18

Netto et al. in a study to determine the effect of hemodynamic pattern on prostate tissue concluded that patients who underwent cardiac surgery using ECC had a significant increase in serum PSA compared to those operated without ECC.7 According to another study, temporary cross clamping of the aorta during CABG had produced prostatic ischemia and infarction and this situation was manifested with an elevation of serum PSA.3 This study also claimed that, there was a correlation between the time on bypass and magnitude of elevation in PSA.3 According to Hagood et al. temporary cross clamping of the aorta during cardiopulmonary bypass (CPB), which led to reduction of blood flow to the lower parts of the body, had been presumed to be the cause of pelvic ischemia.1 They showed that ischemic non-traumatic tissue damage to the prostate during CPB caused an elevation (mean 528%) in postoperative PSA concentration.1 We also discovered elevations of the mean PSA values in the first and fifth postoperative days after CCAB and OPCAB. It can be proposed that a change in the hemodynamic pattern of the lower body which produces an ischemic process on prostate tissue occurs during CABG. This effect is markedly augmented by using ECC in the operation.1,3,7

One could argue that the contribution of urethral catheterization and general anaesthesia has not been taken into consideration in this study, but previous reports had shown that atraumatic urethral catheterization and general anaesthesia per se did not cause a significant elevation in serum PSA.1,4,19 Matzkin et al. and Erdogan et al. had found no change in serum PSA levels in patients undergoing general anaesthesia.4,20 In their controlled study to analyse the effects of urethral catheterization, Hagood et al. concluded that CPB can produce prostatic trauma, possibly due to ischemia during the operation, which causes significant PSA elevation. They also proposed that atraumatic urethral catheterization was unlikely a cause of elevated PSA.1 In accordance with the above mentioned studies, we supposed that the effect of urethral catheterization for all patients in this study would be minimal considering the atraumatic nature and short duration of the procedure.

Non-traumatic elevation of PSA following CABG has been addressed in some previous reports and a few investigators have studied the relationship between CABG and serum PSA levels, but this is the first study in the English literature, which compared the effects of two distinct types of coronary artery revascularization procedures on serum tPSA levels in the early postoperative period, with the evaluation of preoperative comorbidities, operative and postoperative findings of the patients.

In their study, which does not mention about preoperative and postoperative medical status of the patients, Netto et al. had found that the elevation of PSA levels were significantly higher in patients who underwent CABG with ECC when compared to patients who were operated without ECC.7 They had linked this effect to ischemic damage of prostatic tissue which may be more pronounced during CCAB surgery than surgery without ECC. In the present study, we have found the same results and considered that, although other causes of PSA elevation can not be ruled out, an ischemic process in prostate can occur due to all forms of CABG surgery, but as for all the other systems, prostatic tissue may be protected from the deleterious effects of ECC when OPCAB surgery is performed.

Conclusions

Coronary artery bypass grafting is associated with a rise in serum PSA levels in the early postoperative period, possibly due to prostatic ischemic process. This effect is more marked in patients operated with CCAB. Serum PSA levels should be carefully interpreted during the first few postoperative weeks in patients undergoing CABG, particularly when ECC is used.

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