肝移植治疗结直肠癌肝转移的研究进展

结直肠癌是中国常见的恶性肿瘤之一,有研究显示超过50%的结直肠癌患者会发生转移,对于可切除的结直肠癌患者术后辅以系统治疗后有较好的5年生存率,然而对于不可切除的结直肠癌肝转移患者预后往往很差。尽管目前随着医疗的进步,如采取介入联合靶向和免疫治疗等多种方式治疗不可切除结直肠癌肝转移患者,但效果仍然不佳,因此部分临床研究人员将目光转移到了肝移植上。肝移植作为近年来兴起的治疗方式,有望改善不可切除结直肠癌肝转移患者的预后,本文就肝移植治疗不可切除结直肠癌肝转移这一方向做一论述,主要包括肝移植治疗结直肠癌肝转移的历史概况、近期结果、预后因素、适应标准、与系统治疗的关系以及肝源短缺和供者分配等问题,旨在为结直肠癌肝转移患者的肝移植治疗提供参考。     

胃癌肝转移的特点及其外科治疗新理念

20世纪70年代前．实体癌肝转移均被认为是姑息治疗的对象：80年代以后,一些学者相继报道结直肠癌肝转移行肝切除是一种有效的治疗方法。近年来．结直肠癌肝转移的外科治疗已取得良好的效果。然而．胃癌肝转移外科治疗效果仍不理想。日本对胃癌诊治及相关方面研究居国际领先地位．其国立癌中心病院在34年9个月间（1963～1997年）对444例结直肠癌肝转移患者行肝切除术．而同时期．胃癌肝转移行肝切除者仅38例,     

结直肠癌肝及肝外转移外科治疗策略

根治性切除是结直肠癌肝转移唯一有治愈希望的治疗方法。如何提高根治性切除率成为结直肠癌肝转移治疗的主要研究方向。目前认为肝转移灶能否切除不是决定于要切除的部分而是决定于拟保留的肝组织,既要全部切除所有癌灶(R0),又要保留足够的残肝功能,残肝流入、流出道与胆管良好。结直肠癌合并肝脏转移是否同期手术仍存在争议,越来越多的学者认为在不进行较大的肝切除时,同期手术对患者有利。手术切除的边界不再强调"1cm原则",而是强调切缘阴性。以奥沙利铂为基础的新辅助化疗可以使40%原本无手术机会的患者得到根治性切除。合并肝外病变(肺、肝门淋巴结,腹腔转移)时不全是手术禁忌证。肝转移术后复发的再切除长期生存率与首次切除类似。世界许多国家正在制定循证医学基础上的结直肠癌肝转移外科治疗规范。现将结直肠癌肝转移外科治疗策略作一综述。     

同期肝切除治疗结直肠癌同时性肝转移

目的探讨结直肠癌同时性肝转移肝肠同期手术的疗效。方法回顾性分析1994年8月至2004年12月在我院行外科手术治疗的121例同时性结直肠癌肝转移患者的临床资料。结果在121例同时性结直肠癌肝转移患者中,99例行结直肠癌根治性切除术,剔除2例行原位肝移植患者后,同期肝切除组41例（A组）,对肝转移瘤行姑息外科治疗组56例（B组）,即转移瘤未能完全经手术切除者,A、B组患者性别、年龄、原发瘤部位、浸润深度、淋巴结转移等差异均无统计学意义,肝转移瘤数目（x^2=40.41,P＜0.05）、肝转移瘤分布（x^2=11.61,P＜0.05）差异有统计学意义;两组患者中位生存期分别为28.9个月、17.1个月,5年生存率分别为14％、0,其中A组患者中位无瘤生存期为19.5个月,1、3、5年生存率为93%、44%和14%。结论同期肝切除能为部分结直肠癌同时性肝转移患者提供治愈机会,对于合适的患者应力争行同期肝切除术。     

肝切除术治疗转移性肝肿瘤的作用及评价

目前,肝切除术是结直肠、神经内分泌瘤和肉瘤肝转移病人的首选治疗方法,对可切除的非结直肠、非内分泌和非肉瘤的肝转移病人,也是一种安全、值得推荐的治疗方法。转移性肝肿瘤选择肝切除治疗时,应首先评估肝切除的量。综合治疗是提高转移性肝肿瘤病人术后存活率的基本疗法。     

结直肠癌肝转移行肝切除术的疗效分析

目的:探讨结直肠癌肝转移行肝切除的疗效. 方法自1992年至2003年间,对22例结直肠癌肝转移患者行肝切除术,24例肝转移患者行全植入式 (drug deliverly system,DDS)灌注化疗,比较两组患者的治疗效果. 结果在22例行肝切除术的患者中,4例行左肝外叶切除术,3例行左半肝切除术,2例行右半肝切除术,2例行肝段切除术,7例行亚肝段切除术,瘤体局部切除4例.术后1年、3年、5年生存率分别为86.36%、40.91%和31.82% .24例行DDS灌注化疗患者的1年、3年、5年生存率分别为63.64%、12.50%和4.17%. 结论结直肠癌肝转移行各种肝切除术能改善患者的生活质量,延长生存时间.     

手术切除和射频治疗孤立性结直肠癌肝转移的比较研究

孤立性结直肠癌肝转移行肝切除是一种可选择的治疗方法,近年来射频(RF)治疗结直肠癌已被较多采用,但确切治疗作用和疗效尚不明确,缺乏随机临床研究,本研究旨在对手术切除和RF治疗结直肠癌肝转移做一比较研究。病人和方法:共确诊45例结直肠癌肝转移病人,行肝切除20例,因手术禁忌     

肝转移癌的手术治疗

一般来说，肝转移癌的存在意味着肿瘤进展，并表明原发恶性肿瘤的广泛播散。治疗方法包括手术、化疗、放疗和免疫治疗，但只有手术有可能达到治愈。最新报道的手术死亡率低于5％，这表明，肝大部切除能更广泛地用于肝脏转移性肿瘤的治疗。约80％行肝切除术的转移性肿瘤来源于结直肠癌，而另外20%来源于非结直肠肿瘤，因此，有关肝脏转移性肿瘤行肝切除术治疗的资料大部分涉及结直肠癌肝转移。三结直肠癌肝转移40％－50％曾行结直肠癌根治性切除的患者于手术后5年内死亡，其中4／5发现有肝转移，且都于8年内死亡。2581例肝转移癌患者的中位生…     

肝转移癌同期切除的标准

肝切除术是治疗结直肠癌肝转移的唯一有效方法,但如何选择肝切除术的手术时机仍存在较大的争议。在过去的10年中,多数学者建议分期治疗即在结直肠原发病灶切除2～6个月后再行肝转移病灶切除,而现在有研究表明同期切除结直肠原发灶和肝转移病灶在手术死亡率和并发症方面与分期切     

结直肠癌肝转移外科治疗的争议

肝脏是结直肠癌最常见的转移部位,肝转移是结直肠癌治疗失败的主要原因。外科切除在结直肠癌肝转移综合治疗模式中占据主导地位．也是患者获得治愈机会的重要手段。尽管如此,在结直肠癌肝转移外科治疗领域目前还存在很多困惑和争议．包括结直肠癌肝转移分期系统尚不完善、潜在可切除标准尚未统一、可切除肝转移灶是否需要新辅助化疗、根治切除后辅助化疗方案的选择以及不可切除肝转移灶患者无症状原发灶的处理等。本文依据近年来发表的研究资料,结合自身临床实践,剖析肝转移外科研究领域中不同的观点和依据。     

Resection of Noncolorectal and Nonneuroendocrine Liver Metastases: Late Metastases Are the Only Chance of Cure

Resection of liver colorectal metastases allows a 5-year survival in 25% to 35% of patients. The outcome of patients with noncolorectal metastases is unknown because of the heterogeneity of this group. The aim of this retrospective study was to evaluate predictive factors of survival in patients who underwent resection of noncolorectal and nonneuroendocrine (NCRNE) liver metastases. From 1980 to 1997, 284 patients underwent hepatectomy for liver metastases of whom 39 (25 men and 14 women, mean age 55 years) had curative resection for NCRNE liver metastases. No patients had extrahepatic disease. The primary tumors were gastrointestinal (n = 15), genitourinary (n = 12) and miscellaneous (n = 12). The mean number of metastases was 1.8, and the mean size of the lesions was 51 mm. The median disease-free interval was 27 months. Twenty patients had a major hepatectomy and 19 a minor resection, with simultaneous resection of the primary in 6 cases. Overall survival was evaluated using the Kaplan-Meier method. There was no operative mortality, and 8% morbidity. The survival at 1, 3, and 5 years was 81, 40, and 35%, respectively. Patients with a disease-free interval higher than 24 months had a greater survival rate than those with a disease-free interval of less than 24 months (100% vs. 10%; p = 0.0004). Survival was not significantly influenced by age, sex, type of primary tumor, number, size and localization of metastases, type of hepatectomy, or blood transfusion. Resection of NCRNE liver metastases should be justified for patients without extrahepatic disease and resectable metastases, especially for those who have a disease-free interval of more than 24 months.     

Liver Resection for Noncolorectal,Nonneuroendocrine Metastases

In noncolorectal, nonendocrine liver metastases, the role of surgery is less define than in colorectal or neuroendocrine cancer. This role is marginal as liver is not the primary site of metastases of these cancers. Less than 2 to 5% of the patients with these malignancies might be one day considered as potential candidates for liver resection, as most patients suffer from extra hepatic tumour spread at the time they develop liver involvement. However, in these few cases with liver metastases only, as no other therapeutic option may provide mid-or long-term tumour-free survival, liver resection is indicated in resectable liver metastases. Some prognostic factors have been established in the literature from the few published series: unique versus multiple hepatic metastases, unilobar vs bilobar, metachronous vs synchronous, R0 vs R1 or R2 liver resections. The type of primary tumour is also of great importance, as cutaneous melanoma, pancreatic and gastric adenocarcinoma have a very bad prognosis for liver resection of metastases, even after R0 resection. In these cases, percutaneous or laparoscopic radiofrequency ablation may find its place. In sarcoma, breast carcinoma, uveal melanoma, and genitourinary cancers, liver resection may provide satisfactory long-term results in selected cases, and is the standard of care for isolated, resectable metastasis. However, due to the scarcity of indication of liver resection for noncolorectal, nonneuroendocrine metastases, the decision should be multidisciplinary, and the patients should be informed of the advantages and pitfalls of the surgical procedure.     

Liver resection for noncolorectal, nonneuroendocrine metastases

In noncolorectal, nonendocrine liver metastases, the role of surgery is less define than in colorectal or neuroendocrine cancer. This role is marginal as liver is not the primary site of metastases of these cancers. Less than 2 to 5% of the patients with these malignancies might be one day considered as potential candidates for liver resection, as most patients suffer from extra hepatic tumour spread at the time they develop liver involvement. However, in these few cases with liver metastases only, as no other therapeutic option may provide mid- or long-term tumour-free survival, liver resection is indicated in resectable liver metastases. Some prognostic factors have been established in the literature from the few published series: unique versus multiple hepatic metastases, unilobar vs bilobar, metachronous vs synchronous, R0 vs R1 or R2 liver resections. The type of primary tumour is also of great importance, as cutaneous melanoma, pancreatic and gastric adenocarcinoma have a very bad prognosis for liver resection of metastases, even after R0 resection. In these cases, percutaneous or laparoscopic radiofrequency ablation may find its place. In sarcoma, breast carcinoma, uveal melanoma, and genitourinary cancers, liver resection may provide satisfactory long-term results in selected cases, and is the standard of care for isolated, resectable metastasis. However, due to the scarcity of indication of liver resection for noncolorectal, nonneuroendocrine metastases, the decision should be multidisciplinary, and the patients should be informed of the advantages and pitfalls of the surgical procedure.     

Changes in Indication and Results After Resection of Hepatic Metastases From Noncolorectal Primary Tumors: A Single-Institutional Review

Background

The isolated occurrence of noncolorectal liver metastases is rare. The available data are inconsistent in terms of indication for surgery, treatment, and outcome, so a generally applicable therapeutic algorithm is currently lacking.

Methods

A total of 162 patients underwent resection for noncolorectal liver metastases between 1978 and 2001. The patients were divided into two groups from different time periods (group 1, 1978–1989; group 2, 1990–2001) that were similar in terms of number of patients, operating surgeons, and surgical techniques used. The groups were compared, and the data were retrospectively analyzed with regard to indication, survival, and factors predictive for survival.

Results

Resection was performed to remove liver metastases from noncolorectal gastrointestinal carcinoma (n = 50), neuroendocrine tumors (n = 12), genitourinary primary tumors (n = 11), breast carcinoma (n = 24), leiomyosarcoma (n = 15), and metastases from other primary cancers (n = 50). Extrahepatic tumor involvement was seen in 38 (23%) of the 162 cases. Sixty-two (38%) major hepatectomies and 100 (62%) minor resections were performed. In 100 (62%) of 162 patients, a curative resection (R0) could be achieved. Overall 2- and 5-year survival rates of 49% and 26%, respectively, were observed, and the median survival was 23 months. Survival was significantly longer in patients who underwent an R0 resection.

Conclusions

In selected patients, resection of noncolorectal liver metastases is associated with a 5-year survival rate of up to 50%. Resection of liver metastases from gastrointestinal adenocarcinomas correlates with a poor prognosis. Extrahepatic metastases may be considered a relative contraindication for liver resection.

     

Partial hepatectomy for metastases from noncolorectal, nonneuroendocrine carcinoma

OBJECTIVE: To define perioperative and long-term outcome and prognostic factors in patients undergoing hepatectomy for liver metastases arising from noncolorectal and nonneuroendocrine (NCNN) carcinoma. SUMMARY BACKGROUND DATA: Hepatic resection is a well-established therapy for patients with liver metastases from colorectal or neuroendocrine carcinoma. However, for patients with liver metastases from other carcinomas, the value of resection is incompletely defined and still debated. METHODS: Between April 1981 and April 2002, 141 patients underwent hepatic resection for liver metastases from NCNN carcinoma. Patient demographics, tumor characteristics, treatment, and postoperative outcome were analyzed. RESULTS: Thirty-day postoperative mortality was 0% and 46 of 141 (33%) patients developed postoperative complications. The median follow up was 26 months (interquartile range [IQR]) 10-49 months); the median follow up for survivors was 35 months (IQR 11-68 months). There have been 24 actual 5-year survivors so far. The actuarial 3-year relapse-free survival rate was 30% (95% confidence interval [CI], 21-39%) with a median of 17 months. The actuarial 3-year cancer-specific survival rate was 57% (95% CI, 48-67%) with a median of 42 months. Primary tumor type and length of disease-free interval from the primary tumor were significant independent prognostic factors for relapse-free and cancer-specific survival. Margin status was significant for cancer-specific survival and showed a strong trend for relapse-free survival. CONCLUSIONS: Hepatic resection for metastases from NCNN carcinoma is safe and can offer long-term survival in selected patients. Hepatic resection should be considered if all gross disease can be removed, especially in patients with metastases from reproductive tract tumors or a disease-free interval greater than 2 years.     

结直肠癌肝转移灶首次切除和复发后第二次切除对比的Meta分析

目的比较结直肠癌肝转移灶首次切除和复发后第二次切除临床疗效和安全性.方法检索1992年1月至2010年6月间发表的有关结直肠癌肝转移灶首次切除和复发后第二次切除对比的研究,按纳入和排除标准筛选后质量评分,提取临床效应指标,进行Meta分析.结果 22篇文献共计3750病例入选本次Meta分析.较之首次切除,复发后第二次切除手术时间增加平均39 min（P＜0.00001,95% CI=-65.21~-23.13）;术中输血量增加1.1 U（P＜0.00001,95% CI=-1.75~-0.79）.术后ICU住院时间,术后失血及术后住院时间差异没有统计学意义.术后总并发症发生率及具体并发症发生率、远期疗效1年、3年、5年生存率、无瘤生存期及复发率差异没有统计学意义.结论与结直肠肝转移灶首次切除比较,复发后第二次切除具有其相似的手术安全性和有效性.复发后手术切除为首选方案,但是为了获得更有效的远期疗效,应进一步考虑综合治疗.     

Treatment strategy for hepatic metastases of colorectal cancer

Over the past 25 years, 125 patients with colorectal liver metastases underwent 167 hepatectomies in our department. The 1-, 3-, and 5-year survival rates after the initial hepatectomy were 90%, 58%, and 51%, respectively, and those after repeated hepatectomy were 88%, 60%, and 42%, respectively. The predictive factors significantly associated with poor prognosis after initial hepatectomy were maximal diameter of metastasis (> or = 5 cm), distribution pattern in the liver (multiple bilobar), number of nodules (> or = four), and presence of extrahepatic metastases. A disease-free interval of > 6 months after initial hepatectomy was a significant factor for prolongation of survival after repeat hepatectomy. Patients with hilar node metastases at the initial hepatectomy did not receive a survival benefit from hepatectomy, while 5 patients underwent repeat hepatectomy with lymphadenectomy for remnant liver and hilar node metastases with a disease-free interval of > 8 months and 4 of them survived for > 5 years. Our treatment strategies for colorectal hepatic metastases are as follows: 1) hepatectomy is the first choice for < 4 liver metastases without extrahepatic disease; 2) a careful evaluation for liver resection is performed for patients with > or = 4 liver metastases receiving hepatic arterial infusion chemotherapy because of the high frequency of hepatic and/or extrahepatic recurrence after initial hepatectomy; 3) the presence of hilar node metastases at the initial hepatectomy should be excluded from surgical indications; 4) simultaneous single metastasis limited to the lung is an indication for lung resection; and 5) a suitable indication for repeat hepatectomy for hepatic recurrence is patients with a longer disease-free interval. Aggressive surgery based on the optimum patient selection can contribute to clinical benefit, including long-term survival in patients with colorectal liver metastases.     

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.     

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??Role and evaluation of hepatectomy in the treatment of liver metastases YANG Jia-mei. Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, Shanghai 200438??China
Abstract At present, curative hepatectomy is still the first choice of therapy for colorectal, neuroendocrine and sarcoma liver metastases, and seems to be a safe and promising management for patients with resectable non-colorectal, non-neuroendocrine and non-sarcoma metastases of the liver. The volume of hepatic resection should be evaluated firstly when patients with liver metastases will be treated by hepatic resection. But comprehensive treatment will remain as essential first line therapy for most patients with liver metastases improving the survival after hepatectomy.     

The Role of Liver Resections for Noncolorectal,Nonneuroendocrine Metastases: Experience With 142 Observed Cases

Background To evaluate the role of liver resection for noncolorectal, nonneuroendocrine metastases, indications and results were retrospectively reviewed in 142 observed patients.Methods A curative liver resection was performed in 83 cases (58.5%), and the remaining 59 patients received palliative treatments. The primary tumor site was gastrointestinal in 18, breast in 21, genitourinary in 15, leiomyosarcoma in 10, and other in 19. The mean number of metastases was 1.4. The mean diameter of the nodules was 5.7 cm. Liver metastases were synchronous in 11 (13.3%) cases and metachronous in the remaining 72 (86.7%).Results There was no operative mortality. Postoperative morbidity was 20.5%. The median postoperative stay was 9.5 days. The 3- and 5-year actuarial survival rate was 49.5% and 34.3% in resected cases, respectively, whereas there were almost no survivors 3 years after diagnosis in unresected cases (P < .05). The 3- and 5-year disease-free survival was 41.4% and 23.8%, respectively. Among the 83 resected cases, the 3- and 5-year actuarial survival was 17.3% and 8.6% for metastases from gastrointestinal tumors, 53.9% and 24.6% from breast cancer, 63.7% and 36.4% from leiomyosarcoma, 50.4% and 37.8% from genitourinary neoplasms, and 55.6% and 42.4% from other sites, respectively. Fifteen patients (18.1%) survived longer than 5 years.Conclusions Liver resection is an effective treatment for noncolorectal, nonneuroendocrine metastases; it allows satisfactory long-term survival with an acceptable operative risk in selected patients. Hepatic metastases from gastrointestinal carcinoma have the worst prognosis; those from genitourinary tumors show a better outcome. Patient selection is the key to achieving encouraging results.