Carter J J, Whelan R L
Department of Surgery, Columbia University College of Physicians and Surgeons, New York, New York, USA.
Surg Oncol Clin N Am. 2001 Jul;10(3):655-77.
The last decade has seen the publication of many studies regarding the impact of both traditional open methods and minimally invasive techniques on a variety of immune function parameters. Clearly, major surgery results in period of cell-mediated immunosuppression that can have an impact on the patient's recovery that would best be avoided. Although there are conflicting data among studies regarding some immune parameters there is general agreement in regards to other variables. The DTH and LPA studies uniformly have shown that open methods result in significantly more immunosuppression than laparoscopic techniques. It seems that the choice of surgical approach does not impact on the absolute number of lymphocytes or lymphocyte subpopulations. There is evidence of a short-lived (less than 1 day) greater shift towards Th2 function, mainly through suppression of the Th1 lymphocyte population, after open surgery than after closed procedures. Regarding circulating monocytes, laparotomy seems to result in greater decreases in HLA-DR expression and monocyte-mediated cytotoxicity while at the same time activating monocytes to elaborate more TNF-alpha and superoxide anion than laparoscopic methods. The data regarding peritoneal macrophages is most confusing; however, most studies do agree that laparotomy results in increased release of cytokines and respiratory burst mediators. The degree to which CO2 pneumoperitoneum suppresses macrophage function is uncertain because, although some studies have shown that CO2 pneumoperitoneum suppresses macrophage function in regards to control animal results, other studies found that the CO2 and control group results are similar. It also is impossible to draw a firm conclusion in regards to the bacterial clearance studies presently. Similarly, the data regarding NK cell counts and function conflict also to the point that a definite conclusion cannot be made. Serum cortisol levels are similar after both types of surgery. The clear majority of the data suggests that open surgery is associated with significantly higher levels of IL-6 and CRP. Minimally invasive methods are less stressful, as judged by these parameters. It seems that one way to avoid or minimize immunosuppression after surgery is to use minimally invasive methods. In theory, based on the animal evidence reviewed in the previous text, laparoscopic cancer resection methods may be associated with improved long-term oncologic outcome. There is no human evidence to support this hypothesis. Middle range results from nonrandomized human cancer colectomy studies, thus far, have yielded outcomes similar to those following open surgery. The incidence of incisional tumor recurrences is similar after both open and closed approaches. The results of the randomized prospective colectomy trials are anxiously awaited. If, as is the case with closed methods, merely preserving the majority of an animal's immune function after surgery lowers the chances of tumor cells establishing metastases, then purposefully stimulating the immune system perioperatively may be a way to avoid the detrimental effects of laparotomy. Such up-regulation of immune function also might improve further the oncologic results after minimally invasive cancer surgery. The early postoperative period may be an ideal window for immune-based anticancer therapies because the tumor burden is at its absolute lowest immediately following resection of the primary. There is strong evidence in the animal setting that a whole host of agents that broadly stimulate the immune system are effective in reducing significantly the incidence of tumor metastases and the growth of tumors after surgery. There also is preliminary evidence that suggests that preoperative tumor vaccines may be an effective means of establishing specific immune responses against the tumor before resection. In theory, the combination of nonspecific perioperative immune up-regulation and preoperative tumor vaccines would provide the patient with the ability to kill tumor cells immediately following surgery period through specific and innate (i.e., nonspecific) immune responses. The arrival of advanced laparoscopic methods for the resection of cancers has led to research that has made it clear that surgery has important detrimental immune consequences. This work also has suggested novel means to avoid postoperative immunosuppression. Minimally invasive methods may be associated with oncologic advantages that go well beyond less pain, a quicker recovery, and a shorter length of stay. More basic science and human studies are needed to shed more light on this intriguing area.
在过去十年中,发表了许多关于传统开放手术方法和微创技术对各种免疫功能参数影响的研究。显然,大手术会导致细胞介导的免疫抑制期,这可能会对患者的恢复产生影响,最好避免这种情况。尽管关于某些免疫参数的研究数据存在冲突,但在其他变量方面存在普遍共识。迟发型超敏反应(DTH)和淋巴细胞增殖试验(LPA)研究一致表明,开放手术方法导致的免疫抑制明显比腹腔镜技术更多。手术方式的选择似乎不会影响淋巴细胞或淋巴细胞亚群的绝对数量。有证据表明,开放手术后与闭合手术后相比,主要通过抑制Th1淋巴细胞群体,会出现向Th2功能的短暂(少于1天)更大转变。关于循环单核细胞,剖腹手术似乎会导致HLA-DR表达和单核细胞介导的细胞毒性更大程度的降低,同时与腹腔镜方法相比,会激活单核细胞以释放更多的肿瘤坏死因子-α(TNF-α)和超氧阴离子。关于腹膜巨噬细胞的数据最令人困惑;然而,大多数研究确实同意剖腹手术会导致细胞因子和呼吸爆发介质的释放增加。二氧化碳气腹抑制巨噬细胞功能的程度尚不确定,因为尽管一些研究表明,与对照动物结果相比,二氧化碳气腹会抑制巨噬细胞功能,但其他研究发现二氧化碳组和对照组的结果相似。目前关于细菌清除研究也无法得出确凿结论。同样,关于自然杀伤(NK)细胞计数和功能的数据也相互矛盾,以至于无法得出明确结论。两种手术类型后的血清皮质醇水平相似。绝大多数数据表明,开放手术与显著更高水平的白细胞介素-6(IL-6)和C反应蛋白(CRP)相关。根据这些参数判断,微创方法的应激较小。似乎避免或最小化术后免疫抑制的一种方法是使用微创方法。理论上,根据前文回顾的动物证据,腹腔镜癌症切除方法可能与改善长期肿瘤学结果相关。目前尚无人体证据支持这一假设。迄今为止,非随机人类结肠癌切除术研究的中期结果与开放手术后的结果相似。开放和闭合手术方式后切口肿瘤复发的发生率相似。人们急切期待随机前瞻性结肠切除术试验的结果。如果与闭合手术一样,仅仅在手术后保留动物的大部分免疫功能就能降低肿瘤细胞形成转移的几率,那么在围手术期有目的地刺激免疫系统可能是避免剖腹手术有害影响的一种方法。这种免疫功能的上调也可能进一步改善微创癌症手术后的肿瘤学结果。术后早期可能是基于免疫的抗癌治疗的理想窗口,因为在切除原发肿瘤后,肿瘤负荷立即处于绝对最低水平。在动物实验中有强有力的证据表明,一系列广泛刺激免疫系统的药物能有效显著降低术后肿瘤转移的发生率和肿瘤的生长。也有初步证据表明,术前肿瘤疫苗可能是在切除前建立针对肿瘤的特异性免疫反应的有效手段。理论上,围手术期非特异性免疫上调和术前肿瘤疫苗的联合应用将使患者能够通过特异性和先天性(即非特异性)免疫反应在手术后立即杀死肿瘤细胞。先进的腹腔镜癌症切除方法的出现引发了相关研究,明确表明手术具有重要的有害免疫后果。这项工作还提出了避免术后免疫抑制的新方法。微创方法可能具有的肿瘤学优势远不止于疼痛减轻、恢复更快和住院时间更短。需要更多的基础科学和人体研究来更深入地了解这个有趣的领域。