结肠直肠癌肝转移的射频消融治疗

目的:评价结直肠癌肝转移(colorectal cancer liver metastases,CRLM)射频消融(radiofrequency ablation,RFA)治疗的可行性.方法:2003年12月至2008年11月67例结直肠癌肝转移患者在西安交通大学医学院第一附属医院接受了RFA治疗.根据实施RFA治疗的方法将患者分成3组:经皮穿刺RFA(第1组)、开腹RFA(第2组)或经皮RFA与手术相结合的方法(第3组).结果:RFA后90天,3组的死亡率均为零.一半的患者(34/67)出现手术后轻度发热.1/4的患者(17/67)有右肩部与右季肋部疼痛或不适.1例并发结肠瘘.随访显示1年、3年和5年生存率分别是100％、34.3％和4.5％.结论:对CRLM的患者,RFA或结合肝切除手术是相对微创、安全可行的方法,而且致死率低.     

Prognostic factors for transarterial chemoembolization combined with sustained oxaliplatin-based hepatic arterial infusion chemotherapy of colorectal cancer liver metastasis

Objective:To investigate the prognostic factors in chemorefractory colorectal cancer liver metastasis (CRCLM)patients treated by transarterial chemoembolization (TACE) and sustained hepatic arterial infusion chemotherapy (HAIC).Methods:Between 2006 and 2015,162 patients who underwent 763 TACE and HAIC in total were enrolled in this retrospective study,including 110 males and 52 females,with a median age of 60 (range,26-83) years.Prognostic factors were assessed with Log-rank test,Cox univariate and multivariate analyses.Results:The median survival time (MST) and median progression-free survival (PFS) of the 162 patients from first TACE/HAIC were 15.6 months and 5.5 months respectively.Normal serum carbohydrate antigen 19-9 (CA19-9,＜37 U/mL) (P＜0.001) and carbohydrate antigen 72-4 (CA72-4,＜6.7 U/mL) (P=0.026),combination with other local treatment (liver radiotherapy or liver radiofrequency ablation) (P=0.034) and response to TACE/HAIC (P＜0.001) were significant factors related to survival after TACE/HAIC in univariate analysis.A multivariate analysis revealed that normal serum CA19-9 (P＜0.001),response to TACF/HAIC (P＜0.001) and combination with other local treatment (P=0.001) were independent factors among them.Conclusions:Our findings indicate that serum CA19-9 ＜37 U/mL and response to TACE/HAIC are significant prognostic indicators for this combined treatment,and treated with other local treatment could reach a considerable survival benefit for CRCLM.This could be useful for making decisions regarding the treatment of CRCLM.     

Complications related to hepatic arterial infusion chemotherapy for liver metastasis from colorectal cancer

We evaluated the complications of hepatic arterial infusion (HAI) chemotherapy in patients (pts) with hepatic metastasis from colorectal cancer. The subjects consisted of 61 pts with hepatic metastasis from colorectal cancer, who were treated by combined chemotherapy with 5-FU and CDDP weekly or continuously. Indwelling route of catheter: 30 via gastroduodenal artery (GDA) at the time of laparotomy ('LP'), 21 via femoral artery (FA) and catheter tip in PHA ('PHA'), 10 via FA and catheter tip is inserted with steel coil into the GDA ('GDA-coil'). Complications resulting in interruption of therapy occurred in 19 pts (31%), and the 'GDA-coil' method had a lower rate of complication than others. There was no difference in the incidence rate of complications between the two chemotherapy regimens. The complications of this therapy were: 8 (13%) cases of hepatic arterial occlusion, 3 (5%) cases of duodenal ulcer, 4 (7%) cases of catheter tip dislocation, 2 (3%) cases of catheter tip dislocation to the duodenal bulb, and 1 (2%) case of liver abscess. Hepatic arterial occlusion occurred frequently in LP. Up to 67% of patients with duodenal ulcer had hepatic arterial occlusion at the same time. All pts with catheter tip dislocation were 'PHA', and all pts with catheter tip dislocation to the duodenal bulb were 'LP'. In conclusion: 1. The best indwelling route for the catheter is by the 'GDA-coil' method. 2. To diagnose complications soon, regular CTA or DSA is necessary.     

Evaluation of intermittent hepatic arterial infusion chemotherapy for multiple liver metastasis of colorectal cancer

Five patients with synchronous multiple hepatic metastasis of colorectal cancer were treated with hepatic arterial infusion chemotherapy. All cases received intermittent 5-FU infusion (5-FU 250-1,000 mg/2-3 hrs/1-2 weeks) on an outpatient basis. In the evaluation of 5 cases, 3 PR and 1 NC were observed. One case administered arterial infusion for adjuvant chemotherapy has no recurrence in liver. In two patients, extra-hepatic metastases were found. In conclusion, this therapy was effective and useful for hepatic metastasis. Moreover, other forms of treatment for extra-hepatic metastasis must be used.     

Pulmonary arterial infusion therapy for lung metastasis of colorectal cancer

We have developed a pulmonary arterial infusion therapy for lung metastasis of colorectal cancer. Catheterization into pulmonary artery followed by occlusion with ballooning enabled the stasis of blood flow in the unilateral lung for 30 minutes. CDDP was infused via catheter to occluded pulmonary artery. Although no serious adverse events occurred in 5 cases, a tumor reduction in size was not observed. Loco-regional therapy for lung metastasis of colorectal cancer is limited because of recent progress of systemic therapy. However, a development of the procedure of pulmonary arterial infusion may enable a future success of local therapy for lung metastasis of colorectal cancer with a new drug, which is effective in such a short time disposure to tumor as 30 minutes.     

Alternating hepatic arterial infusion and systemic chemotherapy for stage IV colorectal cancer with synchronous liver metastasis

Among 41 patients with synchronous liver metastases of colorectal cancer, 15 patients underwent synchronous resection of their liver metastases and achieved a median survival time (MST) of 1,441 days (versus 748 days for the 26 patients without resection, p=0.038), a median relapse-free survival time of 652 days (MST not reached), and a recurrence rate in the residual liver of 20% (3/15 patients). The alternating hepatic arterial infusion and systemic chemotherapy showed partial response (PR) in 6 cases, stable disease (SD) in 8 cases, and progressive disease (PD) in 1 case (n=15/26). They had an objective response rate of 40% (6/15), tumor control rate (>/= SD) of 93.3% (14/15), one-year progression-free survival rate of 35.7%, 50% time to progression of 270 days, one-year survival rate of 76.2%, and two-year survival rate of 50.8% (MST not reached). Grade 3 leucopenia was observed in 2/15 patients (13.3%). These results suggest that the present alternating therapy may become a standard regimen for patients in whom synchronous resection of liver metastases is impossible and patients who have stage IV colorectal cancer with a risk of recurrence in the remnant liver and/or at extrahepatic sites such as the lungs.     

Hepatic arterial infusion of IL-2 and chemotherapy for unresectable liver metastasis from colorectal cancer

We administered interleukin (IL)-2 with mitomycin C (MMC) and 5-fluorouracil (5-FU) by hepatic arterial infusion for the treatment of liver recurrence from colorectal cancer. The regimen consisted of continuous hepatic arterial infusion of IL-2 (7 x 10(5) JRU/day)/5-FU (250 mg/day) for 4 weeks. After those 4 weeks, a weekly hepatic arterial infusion of IL-2 (2.1 x 10(6) JRU)/5-FU (250 mg) was performed more than 4 weeks. MMC (4 mg) was given as a bolus weekly. This therapy resulted in partial response (PR) in one case, progressive disease (PD) in one case, and no change (NC) in one case. The toxicity of the therapy was a slight in all cases. We herein report 3 patients treated with hepatic arterial infusion of IL-2 with MMC and 5-FU for liver recurrence from colorectal cancer. This therapy may be a new strategy for metastatic colorectal cancer.     

Hepatic arterial infusion chemotherapy for liver metastases from colorectal cancer

After randomized studies of hepatic arterial infusion chemotherapy (HAIC) versus systemic chemotherapy for liver metastases from colorectal cancer in the 1980s, the role of HAIC has been unclear and there is still no evidence to support it as the treatment of choice. The high local control, the differences in techniques between Japan and Western countries, the difficulty of detecting pre-treatment extra-hepatic metastases and the fact that HAIC does not control extra-hepatic lesions are the most important points in considering clinical trials of HAIC. Clinical studies on the combination of HAIC using 5-FU and systemic chemotherapy using CPT-11, and then randomized trial of systemic chemotherapy with/without HAIC is required in Japan to reveal the role of HAIC in the management of liver metastases from colorectal cancer. We should understand the importance of our role in this field.     

Evaluation of arterial infusion chemotherapy for liver metastasis from gastric cancer

We evaluated the effectiveness of arterial infusion chemotherapy for liver metastasis from gastric cancer. Nineteen patients (9 synchronous cases, 10 metachronous cases) were treated with hepatic arterial infusion chemotherapy (HAIC). The response rate was 26% (CR 3, PR 2, PD 14), and the median survival time was 357 days after the diagnosis of liver metastasis. The treatment was discontinued in 8 patients because of treatment associated complications and disease progression. Absence of extrahepatic lesion, response of HAIC, and hepatectomy did not improve the prognosis. The combination of systemic chemotherapy with HAIC tended to improve the prognosis. It may be necessary to reevaluate HAIC as a treatment modality for liver metastasis from gastric cancer.     

Intra-arterial infusion therapy for unresectable liver metastasis of colorectal cancer

Fifty-five colorectal carcinomas with metastatic liver tumor treated with intra-arterial 5-FU (> 5 g) infusion therapy at six hospitals were investigated retrospectively. The response rate reached 45%. The metastatic liver tumor from the rectum did not respond as well as that from the colon. Six patients could undergo liver resection and the infusion therapy was stopped in eleven patients due to a new extrahepatic lesion. The ratio of serum CEA levels of non-responders before infusion therapy and one month later was significantly higher and their survival period was shortened. This ratio indicated that this therapy could be continued.     

Intraarterial infusion therapy for unresectable liver metastasis of colorectal cancer

Forty-two colorectal carcinomas with metastatic liver tumor at four hospitals were investigated retrospectively. The number of patients in H factor 1, 2 and 3 were 8, 12 and 21, respectively. The diameter of the maximum liver tumor ranged from 10 to 160 mm (average 45 mm). The number of liver tumors were from 1 to 50 (average 7.3). The 6-, 12-, 18-, 24- and 32-month cumulative survival rates were 88, 67, 36, 24%, and 7%, respectively. The response rate reached 45%, and the survival period of the responder was significantly more prolonged than that of the unresponder (p = 0.04). No significant survival periods were recognized in terms of the method of injection, injected drug and the amounts of 5-FU. But the response rate of FP injection was best. Patients serum CEA levels at 1 or 3 months were decreased, and the survival periods were significantly longer than for increased patients. No significant difference was found among the side effects, the amounts of 5-FU, and the method of injection. The patients injected with MMC frequently suffered from G 2 or G 3 side effects.     

Evaluation of intra-arterial infusion chemotherapy for liver metastasis from colorectal cancer

We evaluated the effect of intra-arterial infusion chemotherapy for liver metastasis from colorectal cancer. Of 405 patients undergoing colectomy in our department from July 1993 to February 2002, 38 had liver metastasis. We performed catheterization intra-operatively or postoperatively, and intra-arterial infusion chemotherapy was given for liver metastasis from colorectal cancer. Thirty-eight patients were treated with four different arterial infusion courses that mainly consisted of 5-FU. The 5-year survival rate was 8%. Maximal survival period was 68 months, and mean survival was 22 months. The effective rate was 20% Intra-arterial infusion chemotherapy was a useful treatment for liver metastasis from colorectal cancer. Resection of the liver metastasis was the first choice for operative liver metastases from colorectal cancer, and we performed intra-arterial infusion chemotherapy for patients postoperatively or patients with non-operative liver metastasis.     

Hepatectomy and intraarterial infusion chemotherapy for liver metastasis from colorectal cancer

Hepatectomy and intraarterial chemotherapy for liver metastasis from colorectal cancer have been performed in our department. Intraarterial infusion chemotherapy has also been performed for unresectable liver metastasis. One hundred twenty-seven cases of liver metastasis from colorectal cancer were studied. The cases were divided into groups according to radicability of the original colorectal cancer, whether or not hepatectomy was performed, and whether or not they received intraarterial chemotherapy. Group I is cur C of origin. Group II is cur A or B without hepatectomy. Group III is cur A or B with hepatectomy. Each group was divided into a group without intraarterial chemotherapy (A) and a group with it (B). IA 23 cases, IB 13 cases, IIA 14 cases, IIB 21 cases, IIIA 28 cases, and IIIB 28 cases. The survival rate of group III was better than that of group II. The survival rate of group II was better than that of group I. There was no significant difference in survival rates between IA and IB. The survival rate of group IIB was significantly better than that of group IIA. The survival rate of group IIIB was significantly better than that of group III A. Hepatectomy and intraarterial chemotherapy after hepatectomy for liver metastasis from colorectal cancer were effective.     

Radiofrequency ablation for liver metastasis from gastric cancer

Aims

Several studies have reported the benefit of hepatic resection for metastatic tumor from gastric cancer. However, the value of treatment with radiofrequency ablation (RFA) has not been clearly defined.

Methods

Between Jan 2002 and Dec 2007, 21 patients with primary gastric cancer were diagnosed with synchronous or metachronous liver metastases. All patients were treated with RFA, and the complication, survival, and recurrence rates were assessed.

Results

The postoperative complication rate was 5% (1/21), with no mortality. The median actuarial survival time was 14 months. The 1-yr, 2-yr, 3-yr, and 5-yr survival rates after RFA were 70%, 11%, 5%, and 3%, respectively. With a median follow-up time of 19 months, local recurrence at the RFA site was 19% (4/21). Solitary metastasis had significantly longer survival than multiple lesions after RFA (22 vs 10 months, P = 0.004).

Conclusions

RFA provides a minimally invasive and safe modality of treatment patients with liver metastasis from gastric cancer. Patients with solitary liver lesion were considered appropriate candidates for RFA.     

Rules to carry out hepatic arterial infusion chemotherapy at home for patients with liver metastasis of colorectal cancer

We analyzed the effectiveness and adverse effects of hepatic arterial infusion chemotherapy (HAI) for patients with liver metastasis of colorectal cancer in order to clarify the rules of HAI. We provided HAI to 72 patients after hepatic resection and to 119 patients with unresectable liver metastases. The preventive effect on hepatic recurrence was recognized in the group administered more than 15 g of 5-FU (total dose). The response rate of patients with unresectable metastases was 60.3%. Adverse effects were observed in 65.8% of the patients. It is important to establish a follow-up system in each hospital to treat the patients as soon as possible when patients develop an adverse reaction.     

贝伐珠单抗联合化疗治疗结直肠癌肝转移的疗效观察

目的探讨贝伐珠单抗(BV)联合化疗治疗结直肠癌肝转移的临床疗效。方法选取2013年3月至2015年3月间济宁医学院附属医院湖西医院收治的86例结直肠癌肝转移患者,按入院时间随机分为观察组和对照组,每组43人。对照组患者采用奥沙利铂+亚叶酸钙+氟尿嘧啶(FOLFOX方案)化疗,观察组患者采用BV联合FOLFOX方案化疗。结果观察组疾病控制率高于对照组患者,差异有统计学意义(P<0.05)。两组患者严重不良反应发生率比较,差异无统计学意义(P>0.05)。观察组患者无进展生存时间高于对照组患者,差异有统计学意义(P<0.05)。观察组患者1年和2年生存率均高于对照组患者,差异有统计学意义(均P<0.05);两组患者3年生存率比较,差异无统计学意义(P>0.05)。治疗后,观察组患者上升时间(RT)和平均渡越时间(mTT)均显著升高,差异均有统计学意义(均P<0.05),而对照组的RT和mTT并无显著变化,差异无统计学意义(P>0.05),且观察组在不同检测时间点RT和MTT均高于对照组,差异均有统计学意义(均P<0.05)。结论 BV联合化疗治疗结直肠癌肝转移,可延长患者无进展生存时间,提高1年及2年生存率;超声造影定量参数RT和MTT可用来评估结直肠癌肝转移患者的早期疗效。     

Treatment for patients with liver metastasis from colorectal cancer--expansion of hepatic arterial infusion therapy

The treatment of patients with liver metastasis from colorectal cancer was evaluated. Although surgical resection was the most effective therapy and 5-year survival was 30%, more than two-thirds of the patients were judged unresectable at the beginning of the treatment. Those whose metastasis was judged to be unresectable received hepatic arterial infusion (HAI) of 5-FU therapy. In a comparison of the survival period, patients received more than 15 g of 5-FU were found to have a statistically significant longer survival than those who received less than 15 g. Even though the patients who revealed a PR or CR response with HAI did not survive more than 4 years, we began surgical resection in these patients after HAI therapy. As a result, the 5-year survival rate of patients whose metastasis was unresectable and who underwent surgical resection after successful HAI was 30% which was equal to the result of the patients judged resectable at the beginning of the treatment. Such treatment may become the fundamental treatment for unresectable liver metastasis in the near future.     

Hepatic arterial infusion chemotherapy for colorectal liver metastases

Hepatic metastases are a frequent complication of colorectal cancer. Resection of liver metastases can result in long-term survival. However, the majority of patients have unresectable disease. Alternative methods in Japan for treating these patients are hepatic arterial infusion (HAI) chemotherapy with administration of 1,000 mg/m2 of 5-FU over 5 hours. We summarize the status of HAI chemotherapy in terms of colorectal hepatic metastases today. HAI chemotherapy produced higher response rates compared with systemic chemotherapy, but did not demonstrate elongation of survival time in many trials. Important problems remaining to be solved are the technical aspects of percutaneous implantation of intraarterial catheters connected to a subcutaneous infusion reservoir and studies of combined therapy with systemic chemotherapy. Furthermore, in order to finally determine the position of HAI for colorectal liver metastases, it is necessary to conduct a comparative study versus systemic chemotherapy, using the survival time as the primary end point.     

Effect of hepatic arterial infusion chemotherapy for liver metastasis from gastric cancer

We performed hepatic arterial infusion (HAI) chemotherapy for 4 patients with advanced gastric cancer who had undergone curative resection except for liver metastasis. The main antineoplastic drugs were 5-fluorouracil (5-FU), mitomycin C (MMC) and cisplatin (CDDP). A catheter was inserted into the hepatic artery by interventional radiological techniques in 3 patients and operatively in 1 patient. The response rate for 4 patients was 75% (CR2, PR1, PD1). The adverse events were Grade 3/4 nausea and/or vomiting in 2 cases. The HAI chemotherapy was effective and useful for patients with advanced gastric cancer who had no unresectable lesions except for liver metastasis.