同时性结直肠癌肝转移的外科治疗

结直肠癌是我国常见的消化道恶性肿瘤之一.进展期结直肠癌肝转移的发生率约50%～70%,因结直肠癌死亡的患者中约50%是肝转移所致,如何处理肝转移成为延长结直肠癌患者生存期的关键[1].     

同时性结直肠癌肝转移治疗策略

正同时性结直肠癌肝转移(colorectal cancer with synchronous liver metastases,s CRLM)的治疗,涉及化疗、手术、射频、介入等,对于直肠癌还涉及放疗,化疗又有新辅助、转化、辅助之分,手术也涉及胃肠道及肝脏,有同期切除、分期切除、切除顺序等问题,可以说s CRLM是整个外科中最为复杂的疾病。相比于其他伴有同时性转移的肿瘤来说,s CRLM的发病率高、预后好,手术后5年存活率可达到     

两种手术方案治疗结直肠癌同时性肝转移患者效果观察

探讨不同手术方案对结直肠癌同时性肝转移患者预后的影响。回顾性分析2015年1月—2017年1月76例的结直肠癌同时性肝转移(SCLM)实行根治性手术的患者,随机分为科研组(45例)与参照组(31例)。科研组采取同期手术方式,参照组采取分期手术方式,比较两组患者的手术情况以及患者生存率。结果显示科研组患者手术用时以及住院时间和术中出血量显著低于参照组(P<0.05),两组患者术后不良反应发生率以及生存率相比差异无统计学意义(P>0.05)。结果表明,SCLM患者的预后不受手术时机的影响,但同期手术可降低术中出血量,减少手术总时间以及患者住院时间。     

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.     

结直肠癌肝转移的外科治疗策略

肝脏是结直肠癌最常见的转移部位之一,50％-60％的结直肠癌患者最终出现肝转移,其中同时性肝转移约为15％～25％,异时性肝转移约为22％-50％[1]。未能获得治疗的结直肠癌肝转移（colorectal liver metastases,CRLM）患者中位生存时间只有5～12个月。而肝转移瘤获得根治性切除术后5年生存率可达40％～58％[2],遗憾的是在临床上仅有不到10％的患者获得了根治性的肝切除。     

结直肠癌肝转移外科治疗进展

正结直肠癌是临床上最常见恶性肿瘤之一,在全球恶性肿瘤发病率中排名第三~([1]),国内排名第五~([2]),且发病率随年龄逐渐上升。结直肠癌发展过程中,最常见的转移部位为肝脏,约50%的结直肠癌患者在疾病过程中发生同时性或异时性肝转移,约15%～25%结直肠癌在确诊时同时伴有肝转移。     

努力提高结直肠癌肝转移的切除率

肝脏是结直肠癌转移最常见的靶器官。25％～30％的结直肠癌患者伴同时性肝转移．50％～75％的患者在结直肠癌晚期发生肝转移．并因此而死亡。结直肠癌肝转移（colorectal cancer liver metastasis．CRLM）约占Ⅳ期结直肠癌的60％．不少国家将其作为一个单独疾病来对待。如欧洲成立了结直肠转移治疗组（European Colorectal Metastases Treatment Group,ECMTG）并制定了关于CRLM的共识;英国、加拿大、西班牙均对此有专家共识。     

结直肠癌肝转移治疗的若干进展

<正>据不完全统计[1],全球结直肠癌每年的新发病例约为940000例,其中有15%～25%的患者在初诊时已被确诊有肝转移,而有25%～35%的患者在以后的病程中也会发生     

结直肠癌肝外转移外科治疗进展

结直肠癌远处转移最常见的部位为肝脏,约占33％～60％,手术切除被认为是唯一可能治愈结直肠癌肝转移的治疗方法,结直肠癌肝转移手术后5年生存率达到14％～40％,成为普通外科医生关注的热点。但是结直肠癌转移部位中超过半数为肝外转移或肝转移合并肝外转移,其中肝外转移常带来症状,严重影响了患者生活质量,而且虽然手术治疗是肝转移癌的首选治疗方法,但是不可切除的肝外转移是肝转移癌手术禁忌证,因此,肝外转移癌的治疗日趋被普通外科医生所关注。肝外转移癌较常见的部位为肺、脑、卵巢、骨、肾上腺等,现将结直肠癌肝外转移治疗进展综述如下。     

结直肠癌肝转移19例外科治疗分析

<正>随着生活水平的提高和饮食结构的改变,结直肠癌(colorectal cancer,CRC)在我国普通人群中的发病率有逐年增高的趋势。其远处转移是影响CRC预     

Laparoscopy in the management of colorectal cancer metastatic to the liver

BACKGROUND: This investigation was undertaken to define the value of laparoscopy in the staging of patients with colorectal carcinoma metastatic to the liver. METHODS: The clinical details of 59 consecutive patients with colorectal liver metastases undergoing laparoscopy prior to planned hepatectomy were entered prospectively on a computerized database. All patients were staged preoperatively with thin slice (5-7 mm) helical computed tomography chest, abdomen and pelvis. Synchronous metastases were defined as those found during, or on imaging carried out within 1 month of, colorectal resection. Criteria for laparoscopic unresectability were: (i) histologically proven extrahepatic disease; (ii) bilateral inflow or outflow involvement; (iii) the presence of cirrhosis in patients requiring an extended resection (lobectomy or greater); or (iv) hepatic metastases involving more than six hepatic segments. RESULTS: In 24 patients with synchronous metastases (median age 65 years, range 32-81 years) all were resectable on laparoscopic criteria, of whom 21 were resected. Extrahepatic disease was found at laparotomy in three patients. In 35 patients with metachronous metastases (median age 64 years, range 32-81 years) laparoscopy could not be performed in five patients because of adhesions, and three patients were deemed unresectable on laparoscopic criteria. Of the remaining 27 patients, 25 underwent resection while two proved unresectable. Overall eight of 54 evaluable patients had unresectable disease and laparoscopy correctly identified three patients. CONCLUSIONS: Following computed tomography scan, 15% of patients with metastatic colorectal carcinoma will be found to have unresectable disease. Laparoscopy will identify approximately half. Laparoscopy is of no greater value in staging synchronous versus metachronous metastases.     

Surgical treatment and indication for metastatic lung tumor

Prognostic factors of patients with metastatic lung tumors were evaluated on 72 patients who were treated with pulmonary resection (49 via lateral thoracotomy and 23 via median sternotomy). The 5-year survival rate of these patients was 41.3%. Two factors, i.e., tumor free interval (TFI) and tumor size, significantly affected the survival after surgery. Patients with a longer TFI and smaller tumor(s) were associated with a favorable prognosis. The prognosis, however, was neither affected by the number of metastatic lung tumors nor whether they were unilateral or bilateral. The prognosis of lung metastases from colorectal cancer was the most favorable (61.4% at 5-year). On the other hand, patients with lung metastases from renal cell carcinoma and breast carcinoma showed poor prognosis respectively. As for testicular tumors and bone or soft tissue sarcomas, chemo-sensitivity is the most important prognostic factor. Good responders to prior chemotherapy showed a better prognosis than poor responders. These results urge the reappraisal of the role of surgery in the treatment of metastatic lung tumors and demonstrate that aggressive surgery can be indicated even for multiple or bilateral lung metastases. Nature of metastatic tumors, i.e., their origin and chemo-sensitivity, must be taken into consideration when the indication for surgery is decided.     

结直肠癌肝转移外科手术新理念

结直肠癌肝转移发生率高,约60％结直肠癌患者最终将发生肝转移,其中30％转移灶局限于肝脏,这为外科治疗提供了有利条件。按照传统的外科手术标准只有约10％～15％结直肠癌肝转移适合手术切除,但是随着手术理念的更新、新化疗药和化疗方案的出现、局部消融方法的应用,结直肠癌肝转移可切除病例数正逐渐增多。结直肠癌肝转移患者的5年总生产率从30％提高到60％。     

Surgery for colorectal cancer metastatic to the liver. Optimizing the results of treatment

Overall, hepatic resection appears to be an important means of curing patients with metastatic colorectal cancer isolated to the liver. The only absolute contraindication to surgery was the impossibility of a radical removal of tumor: if residual disease will remain after the hepatic resection, this operation is not indicated. A possible second contraindication to surgery is the presence of tumor in the hepatic or celiac lymph nodes. Such metastases from liver metastases signal a biologic grade of tumor that is almost sure to spread to other sites. However, one patient of the 25 in this group did survive long term when positive lymph node groups were dissected. Further clinical experience with this form of the disease along with trials of regional adjuvant therapies such as intraperitoneal chemotherapy may be needed. The presence of extrahepatic metastases at the time of liver resection should be considered a relative contraindication to this surgery, but if the patient can be made clinically disease free, long-term disease-free survival may result. It seems imperative that all patients with hepatic metastases be evaluated by an experienced hepatic surgeon for a curative resection. If the patient has between one and four metastases, a 25 per cent long-term disease-free survival rate can be expected. Patients who have a radical resection of more than four metastases should be considered to be in an experimental group in whom more data are needed. In our current state of knowledge, making such patients clinically disease free is their only chance for long-term survival. Other factors besides the number of metastases that will affect the prognosis of the patient include the disease-free interval between colorectal resection and liver resection, the pathologic margin of resection on the liver specimen, and the presence or absence of mesenteric lymph node metastases from the primary cancer. These factors should be considered when determining the prognosis in a given patient and should be used as stratification variables in prospective trials. However, from our analysis of available data, these factors should not be considered contraindications to hepatic resection.     

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.     

结肠癌肝转移细胞增殖能力减弱

目的 通过阶梯转移法在裸鼠中筛选出人结肠癌肝转移细胞,然后对结肠癌肝转移细胞的生长增殖能力进行鉴定.方法 通过SW1116细胞株裸鼠皮下连续5次传代后取皮下种植瘤裸鼠结肠原位种植,分别取肝脏转移灶和皮下5代细胞进行原代培养,获得大肠癌肝转移细胞和皮下5代的原代细胞,分别命名为结直肠癌肝转移细胞1代(CHM-1)和皮下第5代(P5),通过CCK-8测生长曲线、流式检测细胞周期以及细胞周期相关的蛋白的免疫细胞化学来对SW1116、CHM-1和P5增殖能力进行检测.结果 细胞增殖实验显示CHM-1生长速度明显慢于SW1116和P5细胞(P＜0.05);流式细胞周期分析中CHM-1细胞G41期(68.390±2.865)%比例高于SW1116(50.440±1.472)%和P5(53.930±2.651)%(P＜0.05),G2期CHM-19(13.530±4.411)%比例要低于SW1116(32.030±5.645)%和P5(29.720±3.559)%(P＜0.05),S期3种细胞差异无统计学意义(18.250±6.901)%、(19.050±4.162)%、(18.930±0.169)%(P＞0.05);免疫细胞化学分析发现细胞周期蛋白Cyclin DI在CHM-1(23.7±4.7)%中的表达比SW1116(30.2±5.1)%和P5(32.1±4.2)%减少(P＜0.05).结论 发现侵袭能力和生长增殖能力具有反向关联,即结肠癌肝转移细胞具有更强的侵袭能力,但生长增殖速度比其他细胞更慢.

Abstract：

Objective To study the proliferation ability of liver metastatic colorectal cancer cells by establishing stepwise metastatic colorectal carcinoma cell model via in vivo selection.Methods SW1116 cells were transplanted into the subcutis of nude mice and serially passaged for 5 times,and then the subcutaneous tumor was implanted into the cecal wall of new nude mice.The liver metastatic lesions and the subcutaneous carcinoma cells of the fifth generation were picked for primary culture.Two cell lines named CHM-1 and P5 were obtained.Proliferation levels were analyzed by testing of cell growth curve,cell cycle analyses by flow cytometry and Cyclin D1 analysis by immunocytochemistry.Results CHM-1 grew much slower than P5 and SW 1116 although there was no difference between P5 and SW 1116 in cell proliferation assay ( P＜0.05 ).Cell cycle analysis revealed that the percentage of cells in G0/G1 phase was higher (P＜0.05) in CHM-1 (68.390 ±2.865)% than in SW1116 (50.440 ± 1.472)% and P5 (53.930 ± 2.651)%,but that in G2/M phase was lower ( P＜0.05 ) in CHM-1 ( 13.530 ± 4.411 )% than in SW1116 (32.030 ±5.645)% and P5 (29.720 ±3.559)% rough there was no difference in S phase ( 18.250 ± 6.901 )%,( 19.050 ± 4.162 )%,( 18.930 ± 0.169 )% ( P ＞ 0.05 ).The expression of cell cycle proteins Cyclin D1 was decreased ( P＜0.05 ) in CHM-1 ( 23.7 ± 4.7 )% as compared with thoseinP5(32.1±4.2)% and SW1116 (30.2 ±5.1)%.Conclusion In the same cell line,there was a reverse relationship between the ability of invasion and proliferation.     

Experience with colorectal carcinoma metastatic to the liver

The predilection of colorectal cancer metastases for the liver is probably the result of several factors, including the blood supply, the "homing" characteristics of the tumor cells, and the state of the liver. Five-year survival rates after hepatic resection for colorectal cancer metastases range from 20 to 40 per cent, and some other patients obtain palliative benefit. The authors discuss the three presentations of liver metastases, operative techniques, and prognostic factors.