射频消融治疗结直肠癌肝转移

近十年来,射频消融在结直肠癌肝转移中的应用日渐增多,但尚未充分彰显其优势。全文就射频消融治疗结直肠癌肝转移的现状、存在的问题以及提升疗效的策略等问题作一探讨。     

结直肠癌肝转移外科治疗体会

[目的]探讨结直肠癌肝转移的外科治疗效果及对临床生存时间的影响。[方法]回顾性分析1998年1月至2007年1月结直肠癌肝转移患者行外科手术治疗22例的资料。[结果]术后随访存活1年者19例，存活3年者9例，存活5年及以上者5例。10例同期行肝切除者平均生存期26个月，7例分期行肝切除者平均生存期30个月。术后发生并发症3例，无手术死亡。[结论]掌握外科手术时机和适应证，积极行肝切除术并创造条件提高手术切除成功率，是提高结直肠癌肝转移患者存活率的关键。     

Carbohydrate Antigens and Liver Metastasis in Colorectal Cancer

A comparative immunohistochemical study was performed to analysethe expression of cancerassociated carbohydrate antigens byprimary and metastatic lesions of colon cancer. We used monoclonalantibodies which reacted with Le^a, Le^x and Tn as well as theirsialylated derivatives. Twenty-one primary lesions in patientswithout metastasis and 26 primary and metastatic lesions inpatients with liver metastasis were studied. Sialyl Le^a wasexpressed by 57% of the primary lesions of patients withoutmetastasis, 65% of the primary lesions of patients with metastasisand 73% of their liver metastases. Sialyl Le^x was expressedby 60% of the primary lesions of patients with and without metastasisas well as by approximately 80% of the liver metastases. SialylLe^a and sialyl Le^x showed strong expressions in the liver metastases,significantly greater than in the primary lesions. The findingsindicate the increased expressions of sialyl Lea and sialylLex to be correlated with liver metastasis of colorectal cancer.     

Current Management of Liver Metastasis From Colorectal Cancer

Purpose of Review

To describe the main components of modern treatment for colorectal cancer (CRC) metastatic to the liver.

Recent Findings

Liver metastasis occurs in 50–60% of patients with CRC, and surgery is the only potentially curative treatment. Surgery should be performed where a complete (R0) resection of all radiologically visible metastases is possible. The presence of extra-hepatic disease no longer precludes liver metastectomy, and combined metastectomy in the liver and the extra-hepatic site can result in acceptable long-term survival. Peri-operative chemotherapy significantly improves PFS and DFS, but not OS. Modern cytotoxic regimens can convert a significant percentage of unresectable patients to resectable status, and the addition of biologic agents can increase the rate of conversion. Several local treatment modalities serve as alternatives, or sometimes as adjuncts, to resection of CRC liver metastasis and systemic chemotherapy.

Summary

The modern approach to CRC with liver metastasis combines surgery, modern cytotoxic and biologic agents, and modern technologies in the field of ablation, radiation, and endovascular access. The result is that long-term survival, and even cure, is now possible.

     

Locally Ablative Non-surgical Management of Colo-rectal Liver Metastasis

Background

Liver is one of the commonest sites of metastasis in colorectal cancer patients. Solitary liver metastasis or oligometastasis are traditionally treated by surgical resection or chemotherapy.

Discussion

There may be a subgroup of these patients who are not suitable for surgery or chemotherapy due to various co-morbid factors. These patients can be treated by novel minimally invasive or noninvasive ablative techniques like interstitial brachytherapy, extracranial stereotactic radiotherapy, and radiofrequency ablation.     

肝癌转移的临床研究

本文对188例原发性肝癌(PLC)患者进行了临床回顾性研究,初步探讨了肝癌远隔转移的发生频率、转移部位、临床表现、治疗、预后及影响因素。结果提示:远处转移率为11.7％,大多在50岁年龄组,以男性为主。早发转移者的肝硬化合并率低,骨转移最常见。转移症状主要是疼痛,转移与肿瘤大小及形态无关,但似与AFP有一定关系。治疗主要为对症处理,死因以重要脏器功能衰竭多见,对转移患者的积极治疗可延长生存期。     

FAK is a Critical Regulator of Neuroblastoma Liver Metastasis

Neuroblastomas express increased levels of gastrin-releasing peptide receptor (GRP-R). However, the exact molecular mechanisms involved in GRP-R-mediated cell signaling in neuroblastoma growth and metastasis are unknown. Here, we report that focal adhesion kinase (FAK), as a critical downstream target of GRP-R, is an important regulator of neuroblastoma tumorigenicity. We found that FAK expression correlates with GRP-R expression in human neuroblastoma sections and cell lines. GRP-R overexpression in SK-N-SH cells increased FAK, integrin α3 and β1 expressions and cell migration. These cells demonstrated flatter cell morphology with broad lamellae, in which intense FAK expression was localized to the leading edges of lamellipodia. Interestingly, FAK activation was, in part, dependent on integrin α3 and β1 expression. Conversely, GRP-R silencing decreased FAK as well as Mycn levels in BE(2)-C cells, which displayed a denser cellular morphology. Importantly, rescue experiments in GRP-R silenced BE(2)-C cells showed FAK overexpression significantly enhanced cell viability and soft agar colony formation; similarly, FAK overexpression in SK-N-SH cells also resulted in increased cell growth. These effects were reversed in FAK silenced BE(2)-C cells in vitro as well as in vivo. Moreover, we evaluated the effect of FAK inhibition in vivo. FAK inhibitor (Y15) suppressed GRP-induced neuroblastoma growth and metastasis. Our results indicate that FAK is a critical downstream regulator of GRP-R, which mediates tumorigenesis and metastasis in neuroblastoma.     

结直肠癌肝转移相关的病理组织学评价

 目的　探讨结直肠癌肝转移的病理组织学特性。方法　对 335例行结直肠癌切除的患者行回顾性病理组织学研究 ,将有肝转移者的病理组织学参数与无肝转移者对比。结果　本组 4 1例 (12 % )有肝转移 ,有肝转移者与无肝转移者诸因素的百分率比较为 :肿瘤大小超过 6cm(5 1%υs 2 8% ;P <0 .0 1) ,肠系膜浸润 (98%υs 6 6 % ;P <0 .0 1) ,淋巴结浸润 (34%υs 15 % ;P <0 .0 1) ,静脉浸润 (2 4 %υs 3% ;P <0 .0 1) ,和淋巴结转移 (85 %υs 39% ;P <0 .0 1)。多元回归分析显示 :与肝转移有关的独立因素是肠系膜浸润、静脉浸润和淋巴结转移。诊断肝转移的精确度最高的是静脉浸润 (88% ) ,最低的是肠系膜浸润(41% )。在 98例有肠系膜和淋巴结转移者中 ,有肝转移者与无肝转移者静脉浸润差异非常显著 (2 6 %υs 6 % ;P <0 .0 1) ,其肠外淋巴结转移差异显著 (6 8%υs 4 7% ;P <0 .0 5 )。结论　结直肠癌肝转移的重要因素是肠系膜浸润 ,静脉浸润和淋巴结转移。其决定因素是静脉...     

FOLFIRI方案治疗结直肠癌肝转移的临床观察

目的观察和评价FOLFIRI方案治疗无法手术切除的结直肠癌肝转移患者的临床疗效和毒副反应。方法32例结直肠癌肝转移患者采用FOLFIRI方案化疗,即伊立替康180mg／m2,静脉滴注90min,dl;CF200mg／m2,静脉滴注2h,dl;5．Fu400mg／m2,静脉推注,dl;5-Fu2400mg／m2,持续静注（CIV）,46h,14d为1周期,2周期为1疗程。治疗2疗程以上评价每例患者的疗效与毒副反应。结果全组患者CR0例,PR13例,SD11例,PD8例,有效率40．6％。中位生存期16mo,TTP9mo。主要毒副反应为乙酰胆碱综合征、迟发性腹泻、中性粒细胞减少和口腔黏膜炎。结论FOLFIRI方案治疗结直肠癌肝转移,疗效令人鼓舞,毒副作用可耐受,是治疗结直肠癌肝转移较为理想的化疗方案之一。     

大肠癌肝转移灶分布与原发癌部位的关系

101例伴有转移的大肠癌患者的肝内转移灶分布情况。16例右半大肠癌伴肝转移患者中，转移灶分布在左、右肝和全肝的分别有1例（6．25％）、10例（62．5％）和5例（31．25％），而在85例左半大肠癌伴肝转移患者中分别为12例（14．11％）、29例（34．11％）和44例（51．76％）。认为右半大肠癌转移主要分布在右肝、而左半大肠癌肝转移主要分布在全肝。     

Serological Diagnosis of Liver Metastasis in Patients with Breast Cancer

Objective To diagnose and explore the serological diagnostic factors for liver metastasis in patients with breast cancer before symptoms occur. Methods A total of 430 female in-patients with breast cancer of stages 0 to IIIC who came to Tianjin Medical University Cancer Institute and Hospital from January 2003 to January 2004 were studied and followed up until May 2011.Serum levels of biochemical markers for tumor and liver were measured at the time of diagnosis. Results Liver metastasis was more likely to occur in patients with stage III cancer or c-erbB-2-positive expression.Alanine aminotransferase,aspartate aminotransferase,γ-glutamyltransferase(GGT),alkaline phosphatase,lactate dehydrogenase(LDH),and carbohydrate antigen 153(CA153) levels were significantly higher in patients with liver metastasis than those without liver metastasis. Diagnostic indices of LDH,GGT,and CA153 were 174 U/L,32 U/L,and 26.48μg/L,respectively.The areas under the curves of LDH, GGT,and CEA were 0.795,0.784,and 0.661,respectively,and sensitivities of parallel tests for LDH and CA153 and for GGT and CA153 were 88.6%and 85.7%,respectively.The specificity of serial tests for both pairs of enzymes was 97.7%. Conclusions The sensitivity and specificity of combined tumor and biochemical markers could be used as indicators during screening for breast-liver metastasis.     

Treatment of Rupture of a Liver Metastasis from Esophageal Leiomyosarcoma

We describe a case of rupture of a liver metastasis from esophagealleiomyosarcoma which was treated successfully by hepatic arterialembolization, thus facilitating hepatectomy. A 59-yearold womanwho had previously undergone esophagectomy for leiomyosarcomawas admitted in a state of hypovolemic shock. Ultrasonographyrevealed multiple tumors in the left lobe of the liver and massiveintraperitoneal hemorrhage, confirmed by paracentesis, possiblydue to spontaneous rupture. Subsequent hepatic angiography showedextravasation from the tumor, and embolization of the feedingleft hepatic artery was performed. After achieving hemostasis,a left hepatic lobectomy was carried out just beneath the reconstructedstomach tube. The patient made an uneventful recovery and remainswell after one year. Emergency arterial embolization followedby hepatectomy is an appropriate treatment for patients withspontaneous rupture of liver metastases.     

Prognostic Significance of Liver Metastasis in Durvalumab-Treated Lung Cancer Patients

IntroductionTwo clinical studies (Study 1108 and ATLANTIC) were analyzed to evaluate the prognostic value of baseline liver metastases (LMs) in advanced/metastatic non–small-cell lung cancer patients treated with durvalumab 10 mg/kg every 2 weeks.Patients and MethodsA multivariate Cox proportional hazards analysis was conducted; covariates included performance status, tumor stage, histology, sex, age, smoking status, and programmed cell death ligand 1 (PD-L1) status.ResultsIn all, 569 patients were included. LMs were present in 31.6% (96/304) of Study 1108 patients and 17.9% (47/263) of ATLANTIC patients. Median overall survival (OS) was shorter in patients with LMs than in those without in both studies. In both studies, LMs were an independent negative prognostic factor for OS and progression-free survival. Objective response rates were also significantly lower. PD-L1 independently predicted benefit across all patients.ConclusionLiver metastases were associated with worse outcomes irrespective of PD-L1 status, but PD-L1 status predicted benefit from durvalumab irrespective of LMs.     

PDGFRB Promotes Liver Metastasis Formation of Mesenchymal-Like Colorectal Tumor Cells

In epithelial tumors, the platelet-derived growth factor receptor B (PDGFRB) is mainly expressed by stromal cells of mesenchymal origin. Tumor cells may also acquire PDGFRB expression following epithelial-to-mesenchymal transition (EMT), which occurs during metastasis formation. Little is known about PDGFRB signaling in colorectal tumor cells. We studied the relationship between PDGFRB expression, EMT, and metastasis in human colorectal cancer (CRC) cohorts by analysis of gene expression profiles. PDGFRB expression in primary CRC was correlated with short disease-free and overall survival. PDGFRB was co-expressed with genes involved in platelet activation, transforming growth factor beta (TGFB) signaling, and EMT in three CRC cohorts. PDGFRB was expressed in mesenchymal-like tumor cell lines in vitro and stimulated invasion and liver metastasis formation in mice. Platelets, a major source of PDGF, preferentially bound to tumor cells in a non-activated state. Platelet activation caused robust PDGFRB tyrosine phosphorylation on tumor cells in vitro and in liver sinusoids in vivo. Platelets also release TGFB, which is a potent inducer of EMT. Inhibition of TGFB signaling in tumor cells caused partial reversion of the mesenchymal phenotype and strongly reduced PDGFRB expression and PDGF-stimulated tumor cell invasion. These results suggest that PDGFRB may contribute to the aggressive phenotype of colorectal tumors with mesenchymal properties, most likely downstream of platelet activation and TGFB signaling.     

Murine Liver Metastasis Model Using L5178Y-ML Lymphoma and the Effect of Antitumor Agents on the Metastasis

A reproducible tumor model for liver metastasis has been developed from murine L5178Y lymphoma line by sequential cycles of subcutaneous inoculation of liver tumor cells, that were originally generated in livers of female (BALB/c × DBA/2)F₁ mice by injecting the parental cells into the tail vein. This variant (L5178Y-ML) metastasized predominantly to the liver after intravenous or subcutaneous injection. The livers of the animals killed 9 days after intravenous implantation of 5 × 10⁵ tumor cells were about 3 times the weight of control livers. All tumor-bearing mice died 10 to 12 days after inoculation. Subcutaneous implantation of L5178Y-ML in the side flank of mice induced metastatic nodules spontaneously in the livers. The tumor cells proliferated more in livers than in the implanted sites, compared with the parental L5178Y cells. The effects of 5-fluorouracil, mitomycin C, cis -platinum and doxorubicin on the liver metastasis of L5178Y-ML were examined at subtoxic doses; 5-fluorouracil was the most effective in both inhibiting the tumor growth in livers and prolonging the survival period of mice. This model provides a useful tool for the experimental therapy of hepatic tumors in mice.     

联合草酸铂经肝动脉灌注治疗复发转移性肝癌

目的：观察草酸铂（奥沙利铂）在肝动脉中灌注治疗复治转移性肝癌的安全性和疗效。方法：对8例复治的转移性肝癌的患者在肝动脉中灌注200mg奥沙利铂,结果：8例患者中,1例患者达到PR,5例患者NC,2例患者PD;毒副反应均为Ⅰ－Ⅱ度,治疗中未出现肾功能的损伤。结论：奥沙利铂动脉灌注是安全的,初步研究证明在肝动脉中灌注有一定疗效。     

应用纯酒精（〉99.5%）经腹腔内直接注射胃癌肝转移：附7例分析

对胃癌肝转移,将胃的原发灶切除之后,涉及肝脏一叶式多叶的,表面的孤立型转移性病灶,不可能作联合肝脏切除的,采用纯酒精(>99.5％)注射,病灶越小越好。包膜型优于非包膜型。本文对7例病人观察,疗效尚满意。此疗法快速、简便、经济、值得推荐。