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.     

结直肠癌肝转移的综合治疗

结直肠癌肝转移是影响结直肠癌预后的重要因素,治疗方案包括手术治疗、化疗(全身静脉化疗和介入治疗)、基因治疗和局部治疗(射频消融、激光消融、无水酒精注射和冷冻切除术)等,其中手术是目前唯一有效的治愈手段,手术死亡率为1%~2.8%,术后5年生存率为34%~38%,但仅有10%~25%结直肠癌肝转移患者确诊时适于手术切除,因此各种非手术治疗的作用正日益受到关注。本文就结直肠癌肝转移的综合治疗作一综述。     

同时性结直肠癌肝转移的外科治疗进展

同时性肝转移占结直肠癌初诊病例的15—25％,是困扰结直肠癌治疗的一大难点和热点。手术治疗目前是结直肠癌及肝转移唯一可能获得治愈希望的治疗手段,切除原发结直肠癌和肝转移病灶术后5年生存率可达34％～38％。但超过85％的初诊患者无法接受手术切除,如何通过综合治疗,提高结直肠癌以及同时性肝转移的手术切除率,延长生存,尤其是同步切除原发和肝转移病灶成为了近期关注的重点。     

再谈结直肠癌肝转移外科治疗新理念

肝转移是影响结直肠癌预后的重要因素[1-2],在众多的治疗方法中仅有手术治疗术后5年生存率为34%～38%[3-4].但超过85%的结直肠癌肝转移初诊患者无法接受手术切除,其中一部分为肝转移灶潜在可切除或伴有可切除肝外转移灶的患者.随着手术观念和技术的革新以及综合治疗手段的不断完善,更多的结直肠癌肝转移患者有获得治愈的希望[5-6].现就结直肠癌肝转移手术适应证概念的更新予以阐述.     

结直肠癌肝转移一期联合手术化疗的临床研究

目的探讨结直肠癌肝转移一期联合手术辅助化疗的有效途径及临床价值.方法回顾性分析一期联合手术切除原发癌及转移癌,经肝动脉门静脉双置泵栓塞灌注化疗,肿瘤局部注射无水酒精及热电疗法综合性治疗结直肠癌肝转移36例的临床资料.结果本组36例结直肠癌患者原发癌均获切除,其中一期切除肝转移癌17例,6例复发,4例再次手术切除.19例不能切除的转移性肝癌,行肝动脉门静脉双置泵栓塞灌注化疗,无水酒精注射和热电疗法.肿瘤直径平均缩小57%,其中4例因肿瘤缩小行二期手术切除.1、2、3年生存率分别为切除组94%,82%,65%;明显高于置泵组的74%,53%,32%(P<0.01).结论结直肠癌肝转移一期联合手术切除加肝动脉门静脉双置泵栓塞灌注化疗,是一种首选而有效的治疗方法.不能切除肝转移癌者,只要切除原发肿瘤,肝动脉门静脉置泵栓塞灌注化疗,可明显延长病人生存期,改善预后.     

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].     

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].     

结直肠癌肝转移的治疗进展

肝脏是结直肠癌转移的最常见器官，10％～25％的结直肠癌患者在确立诊断时即已存在肝转移，另有20％～25％的患者在肠癌术后发生肝转移，因此结直肠癌肝转移的发生率可高达50％，而能获得手术切除者仅占lO％～20％。近年来随着新的化疗药物的应用，局部介入治疗技术的发展，使一部分患者的肝癌缩小而获得二期切除。     

结直肠癌肝转移瘤热消融治疗国际专家共识分享

肝转移是结直肠癌致死的最主要原因,手术切除是其首选治疗方式。然而,临床可手术切除的肝转移瘤仅占全部肝转移瘤的10%~25%,对不可切除的肝转移瘤通常采用系统化疗和/或局部消融治疗。近年来热消融技术的治疗效率和安全性日益提高,术后患者5年生存率高于单纯化疗。2013年国际消融专家组发布了结直肠癌肝转移瘤热消融治疗国际专家共识,基于射频消融相关应用的长期随访文献,总结热消融治疗在结直肠癌肝转移瘤治疗中的具体推荐及相关适应证。本文对该共识的主要内容进行介绍与分享。     

家族性腺瘤性息肉病患者结直肠癌变的外科预防

目的 探讨家族性腺瘤性息肉病(FAP)患者结直肠癌变外科预防的手术时机和术式选择.方法 回顾性分析我院近年来连续诊治的43例FAP患者结直肠癌的发病状况及预防性手术治疗的疗效.结果 未经手术干预的FAP患者,20岁、25岁、30岁、35岁、40岁、45岁、50岁时的累积结直肠癌变风险分别约为0、10.4%、25.3%、32.4%、63.0%、76.9%、86.2%;发生结直肠癌变的病例中有84.6%发生直肠癌变.11例患者在我院接受了预防性手术治疗,无手术死亡,3例全结直肠切除、回肠J-Pouch肛管手工吻合术患者术后并发吻合口瘘.1例结肠次全切除的患者于术后13年直肠癌变.3例回肠J-Pouch肛管吻合患者无肛门失禁,每日排便4～6次.结论 FAP患者预防性手术治疗时机应在20岁之前,最迟不超过25岁,全结直肠切除、回肠J-Pouch肛管吻合器吻合术预防结直肠癌变安全有效,适合作为预防性手术的首选术式.     

Liver resection and transplantation — Therapeutic concepts in surgical treatment of hepatic metastases

Summary Background: Surgical procedures such as liver resection or liver transplantation are the only treatment modalities that provide a chance of cure for patients with liver metastases. Methods: This report reviews results of liver resection and liver transplantation for liver metastases from colorectal cancer and neuroendocrine tumors as compared to the natural course. Results: Overall 5 year survival after curative liver resection for colorectal metastases ranges between 25 and 48%. The operative mortality is between 0 and 5%. Risk factors for tumor recurrence are more or less defined. Reresections of metastases can be performed with comparable mortality rates and results. Liver transplantation for unresectable colorectal metastases offers a median survival of 28 months, but the chance of cure only for individual patients. Exclusion of patients with positive lymph nodes of the primary tumor improves median survival. As there are alternative treatment options for neuroendocrine metastases, indication for liver resection or transplantation is not clearly defined, but the chance of cure by means of surgical treatment should not be missed. Curative resections of neuroendocrine liver metastases can achieve 5-year survival rates of more than 80%. Conclusions: Radical surgical removal of liver metastases from colorectal and neuroendocrine cancer can improve the prognosis for selected patients. Further improval is expected from a multimodal approach.      

Surgical treatment of late metastases of kidney cancer

Whereas 25-57% of patients diagnosed with renal cell carcinoma (RCC) present with metastatic disease, about 50% of (RCC) patients develop metastases after potentially curative radical nephrectomy. Five-year survival at following surgical removal of solitary metastases is approximately 35-50%. Our experience demonstrate that a small cohort of patients benefit from aggressive surgical therapy for consequtively arising solitary distant metastases with long-term palliation.     

Neoadjuvant chemotherapy as a treatment strategy for multiple bilobar liver metastases from colorectal carcinoma

Hepatic resection remains the only potentially curative therapy for patients with colorectal liver metastases. Because most have multiple bilobar liver metastases, surgical resection is possible in only 25-58% of patients with colorectal liver metastases. Currently, attention is focused on the potential for neoadjuvant chemotherapy to render formerly unresectable patients resectable. The availability of more efficacious chemotherapy agents and an inventive approach to delivery schedules have resulted in an increase in the number of candidates for hepatic resection after neoadjuvant chemotherapy. Although tumor response varies with regimen and/or route of chemotherapy for colorectal liver metastases, with 16-63% tumor response rates, hepatic resection for responders after neoadjuvant chemotherapy gives survival benefits, with 20-48% 5-year survival rates after surgery. Provided that neoadjuvant chemotherapy controls multiple bilobar liver metastases well, aggressive hepatic resection should be considered for patients with those lesions. As a treatment strategy for multiple bilobar liver metastases, neoadjuvant chemotherapy is a useful to increase resection rates and may contribute to the improvement of prognosis in patients with such lesions.     

Interventional treatment of neuroendocrine liver metastases

Neuroendocrine gastroenteropancreatic tumours are rare with an incidence of 2-4/100.000 per year. More than 75% of the patients develop hepatic metastases, which reduce the five year survival from 70-80% to 30-40%. In addition to chemo- and biotherapy, interventional therapy of liver metastases should be considered in order to prolong survival and reduce endocrine and local symptoms. Surgical resection is the only curative treatment, but possible in less than 10% of the patients. Curative and palliative resection, which is possible in less than 20-25% of the patients, relieve endocrine and local symptoms in 90% of the patients for more than two years, and the five year survival is prolonged to 40-85%, although metastases recur or progress in almost all patients. Tumour ablation by radiofrequency therapy has a palliative effect on endocrine symptoms in 70-90% of the patients for up to two years, but should not be a substitute for surgical treatment. When metastases are not eligible for surgical treatment or ablation, embolization or chemoembolization are alternative options with a reduction in tumour burden in about 50% and a five year survival of around 60% ofthe patients. The symptomatic response rate is 90% with a mean duration of two years. Liver transplantation should be restricted to very few and highly selected patients without extrahepatic disease. Recurrence is inevitable in nearly all patients.     

Surgical treatment of distant metastases in differentiated thyroid cancer: indication and results

A total of 45 patients have received surgical treatment for distant metastases in 41 follicular and four papillary carcinomas. Fifty-four metastatic lesions were removed. In the majority of cases (n = 25, 46%), surgical intervention was indicated on the basis of oncologic data (reduced administration of radioiodine). Sixteen patients (30%) underwent surgery to relieve pain, and 13 other patients (24%) had surgical treatment of pathologic fracture. At the time of surgery, 29 patients (64%) had only one resectable metastasis, while 16 patients (36%) had further nonresectable metastases (six in the bone, 10 in the bones and lungs). In the course of 53 operations, metastases were resected from bone in 46 cases, from the lungs and greater omentum in two cases, and from the skin, suprarenal gland, pleura, and intra-abdominal lymph node in one case each. A total of 25 metastases (17 bone, eight soft tissue) could be removed by resection. In 16 patients, the resulting bone defect was filled with bone cement after resection of the metastases. Osteosynthesis was necessary in another six cases, while seven required the implantation of an endoprosthesis. Thirty-eight patients died between 1 and 136 months after surgical treatment. Twenty-six (58%) died of their primary disease after an average 49.3 months, seven (15%) died with their carcinomas of other causes after an average of 12 months, and five (11%) died intercurrently after an average of 16 months. Seven patients (15%) are still alive after 12 to 264 months (average, 99.3 months); four of them are without recurrence and three have metastases. Five of these patients exhibit normal activity, while the activity of the other two is limited by the progress of the carcinoma or as a result of surgical treatment. The estimated cumulative survival rate (Kaplan-Meier) was 44.8 +/- 11.2% for 5 years and 32.7 +/- 11.0% for 10 years after removal of a solitary metastasis. Analysis of these patients shows that the surgical removal of resectable metastases can be a valuable complement to nuclear medical therapy. The complicated surgical treatment of metastases is justified by the favorable effect it has on prognosis and on the patient's quality of life.     

结直肠癌同时性肝转移的外科治疗

Synchronous colorectal liver metastases occurs in 15%-25% of patients with newly diagnosed colorectal cancer. Hepatic resoction has been accepted as the only option that offers long-term survival for patients with liver metastases. However, the optimal timing and sequence of resection for synchronous colorectal liver metastases still remain controversial. Also, the use of neoadjuvant chemotherapy which should be initiated in patients with resectable synchronous liver metastases is not consistent. In order to use evidence-based medicine to clarify indications for one-stage hepatic resection of liver metastases, a multi-center clinical trial was pedormed to normalize the surgical strategy of synchronous liver metastases. In summary, in selected patients, one-stage approach is comparable to the two-stage procedure in mortality and morbidity rates and longterm survival. One-stage procedure should be performed according to the site of primary tumor, age, the volume of residual healthy liver. Preoperative chemotherapy is effective in downstaging the tumor and reducing the resected liver volume, but it also brings damage to the liver and has adverse effect on onestage hepatic resection.     

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.     

Outcome After Hepatectomy for Multiple (Four or More) Colorectal Metastases in the Era of Effective Chemotherapy

Background Hepatic resection is generally accepted as the only potential for long-term survival in patients with colorectal metastases confined to the liver. Despite an unknown benefit, hepatic resection is playing an increasing role in patients with extensive disease. Methods A retrospective review of a prospectively maintained hepatobiliary surgical database was carried out. Outcome after hepatectomy for four or more colorectal hepatic metastases was reviewed. Results Between 1998 and 2002, out of a total of 584 patients, 98 (17%) with four or more colorectal hepatic metastases were resected. Actuarial 5-year survival was 33% for the entire group, with seven actual 5-year survivors. There were no perioperative deaths, and the perioperative morbidity was 28%. Positive margins and extrahepatic disease resection were independently associated with poor outcome. The median disease-free survival was 12 months, with no actuarial disease-free survivors at 5 years. Recurrence pattern, response to neoadjuvant chemotherapy, time to recurrence, and resection of recurrent disease were also associated with outcome. Conclusions Long-term survival can be achieved after resection of multiple colorectal metastases; however, because most patients will experience recurrence of disease, effective adjuvant therapy and close follow-up is necessary.     

Hepatic Resection for Colorectal Metastasis: Impact of Tumour Size

Background Many colorectal liver metastasis patients are denied surgical resection on the basis of tumour size. The aim of this study was to explore the impact of metastasis size on modern liver resection.Methods Using a prospectively collected database, this was a retrospective analysis of 484 consecutive patients who underwent liver resection for colorectal liver metastases between 1993 and 2003. The cohort was divided into two groups: smaller metastases (<8 cm) and larger metastases (≥ 8 cm). Those with larger metastases were then further stratified into big metastases (8–12 cm) and giant metastases (>12 cm). Demographic, pathological, surgical technique and outcome data were compared between the groups.Results There were 88 (18%) patients with metastases measuring 8 cm or larger. There was an association between higher carcinoembryonic antigen (CEA) and cancer antigen (CA) 19-9 levels and larger metastases. The actuarial 5-year survival for patients with larger metastases was 38% compared with 42% for smaller metastases (not statistically significant). Patients with giant metastases had poorer overall and disease-free survival (both nonsignificant) compared with those with big metastases: 29% and 28% at 5 years, respectively.Conclusion Patients with colorectal liver metastasis greater than 8 cm and up to 12 cm in size should not be treated differently from those with smaller lesions.     

Cryoablation and liver resection for noncolorectal liver metastases

BACKGROUND: Liver resection for noncolorectal liver metastases has merit for selected primary tumor types. The role of cryosurgical tumor ablation within this cohort of patients has not been evaluated. This is a single institutional review of treatment outcomes using cryosurgical ablation and conventional resection techniques for noncolorectal liver metastases. METHODS: The medical records of 42 patients undergoing 48 hepatic tumor ablative procedures from February 1991 through May 2001 at a single institution were retrospectively reviewed. Overall survival and local hepatic tumor recurrence-free survival were analyzed for different surgical procedures and primary tumor types. RESULTS: Overall survival rates at 1, 3, and 5 years are 82%, 55%, and 39%, respectively (median survival, 45 months). Local hepatic tumor recurrence-free survival rates for resection only (n = 25) and cryosurgery with or without resection (n = 23), at 3 years are 24% and 19%, respectively. The survival rates at 5 years are 40% and 37%, for resection only and cryosurgery with or without resection, respectively. CONCLUSION: Cryosurgical hepatic tumor ablation for metastatic noncolorectal primary tumors results in survival and local hepatic tumor recurrence rates similar to resection alone. The combination of cryosurgery and resection extends the cohort of patients with surgically treatable disease.