Benjamin Ayres, Department of Urology, Level 3 King Edward Building, Bristol Royal Infirmary, Marlborough Street, Bristol. BS2 8HW, UK.




C-reactive protein


human leukocyte antigen.


Laparoscopic surgery is gaining popularity in the treatment of many urological conditions and is now commonplace at specialized centres around the world. Many outcomes are comparable with open surgery, e.g. rates of urinary incontinence and erectile dysfunction are similar in both laparoscopic and open radical prostatectomy [1], and although long-term data are awaited, oncological outcomes are also comparable [2]. However, laparoscopic surgery has several advantages, e.g. reduced blood loss, reduced analgesic requirements, faster recovery and shorter hospital stays [3,4]. Many of these advantages are attributed to reduced tissue trauma and it is therefore thought that laparoscopy also results in less surgical stress.


The stress response is an important consequence of surgery because it results in catabolism and repair, mediated by cytokines, catecholamines, cortisol, insulin, growth hormone and antidiuretic hormone. However, it can be deleterious, especially in patients with concurrent medical conditions and altered physiology. Increased oxygen requirements result in greater cardiorespiratory effort, endogenous substrate stores are depleted and persistence of inflammatory mediators can result in a systemic inflammatory response syndrome and possible multiple-organ failure [5]. In addition, activation of cytokine and other humoral cascade systems by surgical trauma reduces both cellular and cell-mediated immunity, resulting in immunosuppression [6].


Compared with open surgery, many studies show a smaller stress response after laparoscopic procedures, particularly laparoscopic cholecystectomy and gynaecological surgery [6,7]. In these studies, the stress response was assessed by measuring cytokines, especially interleukin (IL)-6 and IL-10, C-reactive protein (CRP), TNF-α and sometimes hormones such as cortisol, adrenaline and insulin. However, there appears to be no difference in stress response when the laparoscopic procedure takes longer than open surgery [6]. This might be due to increased tissue trauma. An example of this was a prospective randomized study comparing laparoscopic (12 patients) and open (10) repair of a perforated peptic ulcer, by Lau et al.[8]. They found no difference in levels of IL-6, CRP or cortisol between the groups, and reported that the laparoscopic group had a significantly longer operating time.


There has been little research into stress and laparoscopic procedures in urology, with most studies concentrating on nephrectomy. A study in dogs compared laparoscopic with hand-assisted laparoscopic nephrectomy [9]. Cortisol levels were found to be proportional to operative duration and were lower at skin closure in the hand-assisted group, where surgery was faster. However, cortisol levels continued to rise in this group and resulted in a significantly higher level at 2 h after surgery. Another animal study comparing these techniques and open nephrectomy again found significantly higher cortisol levels in the hand-assisted than in the laparoscopic group [10]. TNF-α levels were also significantly lower after laparoscopy, although serum levels of IL-1 and IL-6 were similar.

In a clinical study, Japanese researchers grouped several laparoscopic procedures together (laparoscopic radical prostatectomy, nephrectomy, adrenalectomy and hand-assisted nephrectomy) and compared them with a group of open procedures (radical prostatectomy, cystectomy and nephrectomy) [11]. The laparoscopic group had a significantly smaller increase in stress-response mediators, IL-6, IL-10 and granulocytic elastase, than the open group. In addition, the authors linked stress to outcome and found that higher IL-6 levels were associated with longer periods of postoperative fasting and hospital stay.


Open surgery results in significantly greater immunosuppression than corresponding laparoscopic procedures, which is characterized by reduced T lymphocyte function (delayed-type hypersensitivity response), reduced human leukocyte antigen (HLA)-DR expression and sometimes a change in T lymphocyte response (CD4/CD8 ratio) [7,12]. Reduced immunosuppression after laparoscopy could result in improved oncological outcomes, in addition to fewer infections. However, the effect on the immune system is not always different, as was the case when it was investigated in open and laparoscopic nephrectomy [13]. There was a significant difference in CD4 and CD8 levels between the groups, but this was present before surgery. There was no difference in HLA-DR expression or cortisol, adrenaline, noradrenaline, cytokine, TNF-α and CRP levels between the groups.


There is growing evidence that laparoscopy causes an altered stress and immune response when compared with open surgery. This in turn might affect morbidity and recovery after surgery, and might improve oncological outcomes. However, these results have not been reported in all studies, particularly if the laparoscopic procedure is longer. In addition, evidence in urological surgery is sparse. Therefore, with the increasing use of laparoscopic surgery in urology, it is time to conduct stringent prospective studies assessing the effect of laparoscopy on the stress and immune response, correlating any effect, where possible, with clinical outcome.