结直肠癌肝转移的中医药防治

结直肠癌是包括自盲肠至直肠的整个肠段的癌肿,是常见的恶性肿瘤.结直肠癌由于早期临床症状不明显,早期诊断率较低,到临床症状明显时,已多属中晚期.结直肠癌的治疗,目前仍以手术切除为首选方法.结直肠癌手术切除率和治愈率有了一定的提高,但是结直肠癌合并肝转移相当常见,15%～25%的结直肠癌患者发现肿瘤诊断时即有肝转移(同时性肝转移),.在结直肠癌切除后患者随诊中20%～50%将发生肝转移(异时性转移).手术时结直肠癌同期肝转移率为15%～25%[1],20%～35%的肝唯一转移部位[2].因此,迫切需要提高结直肠癌的治疗效果,特别是延长结直肠癌术后患者的生存期,提高生存质量,防治结直肠的肝转移.近十余年来,结直肠癌诊断治疗水平快速提高,在早期结直肠癌的手术根治治疗,中晚期结直肠癌的综合治疗等方面取得了较大进展,结直肠癌患者虽经更为合理的根治性手术,但5年生存率仍徘徊在50%左右,其根本原因在于结直肠癌的转移和复发尚未得到有效控制.因此,转移是结直肠癌治疗的主要障碍,控制转移是决定结直肠癌患者预后的关键因素.中医药在结直肠癌肝转移防治方面占有重要地位.     

结直肠癌肝转移预后评分系统的现状及临床应用

结直肠癌是中国第二常见的恶性肿瘤,其中约50％的患者最终会发生肝转移.有效的全身治疗和积极包括手术在内的局部治疗,是提升结直肠癌肝转移患者疗效的关键.肝切除术后复发是导致结直肠癌肝转移患者死亡的主要原因,不同复发风险的患者治疗选择也有所不同,因此建立有效的结直肠癌肝转移预后评分系统,以指导其个体化治疗至关重要.临床危险...     

结直肠癌肝转移危险及预后因素分析

肝脏是结直肠癌最常见的远处转移器官,结直肠癌病人出现肝转移一般预后较差。结直肠癌肝转移分为同时性肝转移和异时性肝转移,对众多的临床以及病理学特征进行的单因素和多因素回归分析提示,影响结直肠癌发生肝转移的危险因素有：浸润深度、淋巴结转移、癌结节、分化程度、癌胚抗原和糖类抗原等。影响结直肠癌肝转移病人预后的因素有：肝转移灶大小及数目、肝外器官转移、原发灶手术切除、肝转移灶手术切除、全身药物治疗等。因此,手术切除肝转移灶、药物治疗获得手术切除机会等治疗模式能够最大程度地提高结直肠癌肝转移病人的存活率。由众多因素组合起来的评分系统,能够较好地预测结直肠癌肝转移病人的预后。     

结直肠癌肝转移的规范化治疗

结直肠癌发病率逐年升高,超过50％的患者会发生肝转移.随着治疗理念的不断发展以及治疗水平的提高,结直肠癌肝转移目前被认为是潜在可治愈性疾病,其预后也有了显著改善.但是,如何选择治疗方法的问题也随之产生.对于结直肠癌肝转移的规范化治疗,应该包括影像学检查,治疗方式的选择以及多学科团队(MDT)诊断治疗等多个方面,同时应该针对患者制订个体化治疗方案.笔者就结直肠癌肝转移影像学检查方式的选择,不同治疗方法的疗效比较,肝转移灶的外科治疗以及MDT诊断治疗模式等内容进行讨论.     

结直肠癌外科手术的原则与进展

结直肠癌是人类常见的恶性肿瘤之一.早期诊断是改善结直肠癌患者预后的关键,对进展期及晚期肿瘤患者实施规范化的手术和综合治疗也能够改善治疗效果.基于结肠癌的淋巴结转移规律以及完整结肠系膜切除理论,结肠癌的手术治疗已经进入规范化和标准化的时代.而在全直肠系膜切除术(TME)金标准的基础上,直肠癌尤其是低位直肠癌手术方式更需考虑个体化.结直肠癌肝转移虽然是晚期疾病,但关于其治疗的研究非常活跃,对于可切除的结直肠癌肝转移肿瘤,肝切除是标准治疗方法,并且也是惟一可能根治的方法.因此,判断结直肠癌肝转移的可切除性显得尤为重要.外科医师是结直肠癌诊断治疗临床实践的最重要参与者,规范化的诊断与治疗是改善患者预后的关键所在.     

结直肠癌肝转移的治疗进展

影响结直肠癌预后的因素有很多,结直肠癌肝转移就是其中的重要原因之一.肝转移是结直肠癌最常见的血道转移方式,文献报道约10%～25%的结直肠癌患者在接受原发灶的手术治疗时已经出现了肝转移,另有约25%的患者在术后随访中发现肝转移[1,2],50%以上的结直肠癌最终发生肝转移,而肝转移是结直肠癌死亡的主要原因之一.本文就近年来国内外文献对结直肠癌肝转移的诊治进行综述.     

中国结直肠癌肝转移诊断和综合治疗指南(V2020)

肝脏是结直肠癌血行转移最主要的靶器官,结直肠癌肝转移是结直肠癌治疗的重点和难点之一。为了提高我国结直肠癌肝转移的诊断和综合治疗水平,自2008年开始编写《中国结直肠癌肝转移诊断和综合治疗指南》并后续进行了多次修订,以期指导对结直肠癌肝转移患者进行全面评估,个性化地制定治疗目标,开展相应的综合治疗,达到预防结直肠癌肝转移的发生、提高肝转移灶手术切除率和改善5年生存率的目的。本次修订后的2020版《指南》包括结直肠癌肝转移的诊断和随访、预防、MDT作用、手术治疗和局部毁损治疗、可达到"无疾病证据"状态结直肠癌肝转移的新辅助和辅助治疗、无法达到"无疾病证据"状态结直肠癌肝转移的综合治疗等六部分,汇集总结国内外该领域的先进经验和最新成果,内容详尽,可操作性强。     

通过转化治疗提高结直肠癌肝转移手术切除率的新进展

目的了解通过转化治疗提高结直肠癌肝转移手术切除率的外科治疗新进展,评估预后评估模型在肝内转移灶切除术后的应用价值,进一步指导患者术后的综合治疗,从而控制疾病快速进展,改善患者的生存质量。方法收集国内外有关结直肠癌肝转移外科治疗新进展的文献,就结直肠癌肝转移的手术切除指征、预后评估模型以及如何通过转化治疗提高其手术切除率的新进展进行综述。结果通过积极的转化治疗,能够使部分结直肠癌肝转移患者接受手术切除肝内转移灶。对于自始至终均无法接受手术切除肝内转移灶的患者,术前化疗、分子靶向治疗药物、多种介入治疗等转化治疗方案均不失为安全、有效的治疗方法,其对患者的生活质量的提高、生存时间的延长有一定的效果。结论我们应该加强对结直肠癌肝转移转化治疗的重视,积极推动预后评估模型在肝内转移灶切除术后的应用。     

结直肠癌肝转移的外科防治

目的探讨结直肠癌肝转移的防治,对提高患者的长期生存和改善其预后具有重要意义.方法通过手术切除有可能根治的一种实体瘤的转移性病变,对于多发性、无法切除的肝转移则首先选用肝动脉滴注化疗.结果对结直肠癌肝转移的治疗,已从消极转为积极多途径的综合治疗,取得一定的效果.结论结直肠癌肝转移是可以积极预防和治疗的.     

结直肠癌肝转移诊断和综合治疗指南(V 2010)

肝脏是结直肠癌血行转移最主要的靶器官[1-2],结直肠癌肝转移是结直肠癌治疗的重点和难点之一.约有15%～25%结直肠癌患者在确诊时即合并有肝转移,而另15%～25%的患者将在结直肠癌原发灶根治术后发生肝转移,其中绝大多数(80%～90%)的肝转移灶无法获得根治性切除[3-7].结直肠癌肝转移也是结直肠癌患者最主要的死亡原因[1].     

不同阶段结直肠癌肝转移的手术策略

结直肠癌患者容易发生肝转移,手术是目前治疗结直肠癌肝转移的最佳手段。但肝转移的发生时机不同,所采取的手术策略也不同。结直肠癌确诊时发生肝转移的患者,其手术时机一直存在争议;结直肠癌根治术后发生肝转移的患者只要具有手术指征,均应再次实施手术治疗;部分暂不能手术的结直肠癌肝转移患者,多采用化疗、RFA、介入等辅助治疗可使患者重新获得手术机会,但在临床应用中也存在不少困惑。因此,针对不同阶段的结直肠癌肝转移,应采用多学科综合治疗,制订个体化的治疗方案才是改善患者预后的关键。     

Liver transplantation is possible in some patients with liver metastasis of colon cancer

Liver metastases from colorectal cancer are an absolute contraindication for liver transplantation. Aggressive therapy with liver resection and local chemotherapy in selected patients may be able to provide long-term cure. Given the risks of tumor recurrence, whether patients with post chemotherapy complications leading to liver failure should be offered transplantation is a challenging question in an era of limited organ availability. Herein we have presented 2 cases of liver transplantation performed in patients with colorectal cancer metastases treated with liver resection followed by hepatic artery infusion chemotherapy leading to development of sclerosing cholangitis and eventual liver failure. This report demonstrates that liver transplantation may be an option in selected patients with colorectal cancer liver metastases that have been well treated.     

Surgical treatment of liver metastases from colorectal cancer

We analyze our experience over a 10-year period in the surgical treatment of liver metastases from colorectal cancer. Between 01.01.1995 and 08.31.2005 189 liver resections were performed in 171 patients with liver metastases from colorectal cancer (16 re-resections - 2 in the same patient and a "two-stage" liver resection in 2 patients). In our series there were 83 patients with synchronous liver metastases (69 simultaneous resections, 12 delayed resections and 2 "two-stage" liver resection were performed) and 88 metachronous liver metastases. Almost all types of liver resections have been performed. The morbidity and mortality rates were 17.4% and 4.7%, respectively. Median survival was 28.5 months and actuarial survival at 1-, 3- and 5-year was 78.7%, 40.4% and 32.7%, respectively. Between January 2002 and August 2005 hyperthermic ablation of colorectal cancer liver metastases has been performed in 6 patients; in other 5 patients with multiple bilobar liver metastases liver resection was associated with radiofrequency ablation and one patient underwent only radiofrequency ablation for recurrent liver metastasis. In conclusion, although the treatment of colorectal cancer liver metastases is multimodal (resection, ablation, chemotherapy and radiation therapy), liver resection is the only potential curative treatment. The quality and volume of remnant liver parenchyma is the only limitation of liver resection. The morbidity, mortality and survival rates after simultaneous liver and colorectal resection are similar with those achieved by delayed resection. Postoperative outcome of patients with major hepatic resection is correlated with the surgical team experience. The long-term survival was increased using the new multimodal treatment schemes.     

Surgical Therapy for Colorectal Metastases to the Liver

Colorectal cancer is the fourth most common type of cancer in the West and the second leading cause of cancer-related deaths in the United States. Approximately 35 to 55% of patients with colorectal cancer develop hepatic metastases during the course of their disease. Surgical resection of colorectal liver metastases represents the only chance at potential cure, and long-term survival can be achieved in 35 to 58% of patients after resection. The goal of hepatic resection should be to resect all metastases with negative histologic margins while preserving sufficient functional hepatic parenchyma. In patients with extensive metastatic disease who would otherwise be unresectable, ablative approaches can be used instead of or combined with hepatic resection. The use of portal vein embolization and preoperative chemotherapy may also expand the population of patients who are candidates for surgical treatment. Despite these advances, many patients still experience a recurrence after hepatic resection. More active systemic chemotherapy agents are now available and are being increasingly employed as adjuvant therapy either before or after surgery. Modern treatment of colorectal liver metastasis requires a multidisciplinary approach in an effort to increase the number of patients who may benefit from surgical treatment of colorectal cancer liver metastasis.     

Additive Chemotherapie bei Lebermalignomen zur Verbesserung der Operabilität

Complete tumor resection is the only curative option for patients with colorectal liver metastases. Hepatic resection is frequently not possible for technical reasons: because of large tumors, multiple or bilateral metastases, or tumors that are too close to vessels. In these cases chemotherapy might downstage the tumor volume and facilitate secondary curative resection in patients initially not eligible for curative surgery. Treatment with fluorouracil (5-Fu) alone has resulted in disappointing response rates of about 10-20% in patients with colorectal liver metastases, which make these protocols useless in the neoadjuvant setting. Because regional chemotherapy into the hepatic arteria results in significantly higher response rates (40-50%), some studies have documented some success in secondary curative surgery after regional chemotherapy of initially unresectable colorectal liver metastases. However, regional chemotherapy is invasive and therefore not standard therapy for every patient with colorectal liver metastases. Recently new exciting treatment options have become available for colorectal cancer. Combinations of chemotherapy consisting of irinotecan and 5-Fu/FA or oxaliplatin and 5-Fu/FA result in response rates of 50% and can be considered a new standard first-line chemotherapy for patients with metastatic colorectal cancer. Recently, two encouraging retrospective studies have been published with chronomodulated chemotherapy of oxaliplatin and 5-Fu/FA in the setting of neoadjuvant chemotherapy for patients with unresectable colorectal liver metastases. With this multidisciplinary approach, antitumor activity of chemotherapy appears to be translated into a long-term survival benefit and some patients with initially unresectable colorectal liver metastases can potentially be cured. As a consequence, on the premises of close cooperation between surgeons and internists, more patients with metastatic colorectal cancer will be cured in the future.     

OncoSurge: a strategy for long‐term survival in metastatic colorectal cancer

OncoSurge is a combined modality strategy for the management of colorectal cancer with hepatic metastases. It has emerged as a result of new and expanded patient selection criteria for resectability of metastases, coupled with more effective neoadjuvant and postoperative chemotherapy. By bringing together these developments in surgery and medical oncology, the new approach promises to increase significantly the resectability rate and long‐term survival in colorectal cancer patients with liver metastases. Surgery for colorectal liver metastases should now be considered across a range of clinical circumstances that would historically have been contraindications to resection. These contraindications include multiple or bilobar metastases, large tumour size, a Dukes stage C or poorly differentiated primary tumour, synchronous detection of metastases with the primary tumour, disease in elderly patients, or a resection margin of less than 1 cm. None of these criteria should necessarily exclude a patient from resection, because although they may be associated with a less favourable prognosis they do not exclude the possibility of long‐term survival. Non‐resectable extrahepatic disease and portal lymph node involvement, however, remain contraindications to resection in most circumstances. Retrospective studies of neoadjuvant therapy have indicated that a regimen based on low dose oxaliplatin, 5‐fluorourucil (5‐FU) and leucovorin increased the overall resectability rate of patients presenting with hepatic colorectal metastases from 20% to 30%, with 13.6% of patients with unresectable metastases becoming eligible for curative resection. More recently, studies using more potent oxaliplatin‐based regimens have reported significantly higher resectability rates of at least 40%, with 5‐year survival of 50% reported in one large study among patients whose liver metastases were resected after initial neoadjuvant therapy for unresectable tumours. Following resection, postoperative therapy based on a combination of hepatic artery infusion (HAI) and systemic chemotherapy reduces hepatic recurrence and increases survival, but more potent systemic therapy is required to reduce the rate of extrahepatic recurrence. Studies are now in progress combining HAI with oxaliplatin‐based systemic therapy to address this issue. By combining a more inclusive approach to surgery with more effective neoadjuvant and postoperative chemotherapy, the OncoSurge treatment model is likely to increase significantly the number of patients with hepatic colorectal metastases who can be treated with curative intent, and thus has the potential to improve overall patient survival.     

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结直肠癌肝转移发生率高,且临床就诊者大多数肝转移灶为不可切除。尽管关于不可切除结直肠癌肝转移病人原发灶的处理尚有一定争议,但随着结直肠癌原发灶处理经验的积累,多学科综合治疗团队(MDT)模式的开展,转化性治疗思维的应用,"个体化治疗"原则的实施,针对不可切除结直肠癌肝转移病人原发灶的处理逐步形成包括手术切除原发灶在内较合理的综合治疗体系。手术切除、新辅助治疗与姑息治疗的合理选择是改善不可切除结直肠癌肝转移病人生存质量及提高生存期,获得最佳治疗效果的关键。     

Surgical treatment of colorectal liver metastases

Recent advances not only in diagnostic imaging examinations but also in surgical techniques of liver resection have extended the indication of liver resection for colorectal metastases, and accumulated experience has improved surgical outcome. Liver metastases develop in a quarter of patients with colorectal cancer, and of these 30 % are candidates for liver resection under the criteria that liver resection is indicated when all tumors can be removed technically with adequate normal parenchyma left, no extrahepatic metastases are detectable, and the patients is considered fit for surgery. As the 5 year survival rate ranges from 30 % and 40 %, liver resection benefits 9 % to 12 % of patients with liver metastases. Recurrence in the liver remnant after liver resection develops in 40% to 50 %, and repeat liver resection benefits those patients.     

Surgical therapy for recurrent liver metastases from colorectal cancer

Forty percent of patients whose disease recurs after hepatic resection for liver metastases from colorectal cancer initially will have liver-only metastases. We have retrospectively reviewed our experience with repeated surgical treatment for liver-only recurrence after previous hepatic resection for colorectal metastases. Repeated hepatic procedures were performed with no mortality in 10 patients. Intraoperative ultrasound allowed identification of three unsuspected metastases and determination of unresectability of two metastases during 11 procedures. Three patients were free of disease at 31, 41, and 48 months from the first hepatic procedure and at 15, 31, and 43 months from the second procedure. Five patients have remained free of hepatic disease. Patients whose initial metastases were less than 6 cm in diameter and had single liver recurrences after hepatic resection appeared to be the best candidates for further surgical therapy. These data and a review of the literature suggest that surgical treatment of recurrent liver metastases from colorectal cancer can be performed safely, and it is associated with long-term disease-free survival in up to 38% of highly selected patients.