Hepatic resection following systemic chemotherapy for metastatic colorectal carcinoma.

Increasingly effective systemic chemotherapy has improved responses in patients with previously unresectable colorectal hepatic metastases. In the future, response to chemotherapy may define a new population of patients that may benefit from hepatic resection. A retrospective review to determine the safety and effectiveness of potentially curative hepatic resection of metastatic colorectal carcinoma after systemic chemotherapy identified 11 such patients with resections between July 1987 and October 1991. Five patients had unresectable disease confined to the liver, two had hepatic and limited extrahepatic metastases, two had hepatic recurrences after previous hepatic metastasectomy, and two had initially resectable liver metastases. These patients were resected after a mean of 8 months of systemic chemotherapy. Complications, usually minor, occurred in five patients (45%). There were no deaths. Three patients are disease free at 15, 18, and 31 months (mean 21) after hepatic resection. Eight patients have recurred with a median time to recurrence of 8 months. Five patients have subsequently died of recurrent disease. This study suggests that hepatic resection following systemic chemotherapy can be performed safely and may benefit selected patients.     

The impact of hepatic resection on metastatic colorectal cancer

Although liver resection is the accepted treatment for patients with metastatic colorectal cancer to the liver, there remains some controversy as to the criteria for patient selection and its impact on the recurrent disease following the operation. One hundred and sixteen patients underwent liver resection for metastaic colorectal carcinoma over the last 23 years at our institution. The actual survival was 50.5% at 5 years, and 38.6% at 10 years, excluding the 30-day operative mortality rate of 1.7%. Positive hepatic lymph nodes, extrahepatic disease, number of tumors (4 or more), and bilobar distribution of the diseases were strongly associated with poor outcome. These prognostic factors were also documented as the major prognostic determinants by 21 consecutive articles we reviewed. Among 52 (45.6%) patients with hepatic recurrence, patients who were acceptable surgical risks and had no extrahepatic diseases or a limited number (one or two) of lung metastasis were candidates for the repeat resection. Consequently, 31 patients underwent repeated hepatic resection. Their survival rate was 53.9% at 3 years and 32.3% at 5 years, with no mortality. This outcome is markedly better than that of untreated patients with an estimated survival of 3 to 24 months. Thus, an aggressive approach to surgical treatment is feasible with low risk and the potentially curative strategy even for recurrent hepatic metastases, providing the opportunity to achieve 5 year survival.     

肝动脉药盒灌注氟脲苷联合全身化疗治疗不可切除老年结直肠癌肝转移

目的 探讨经肝动脉药盒灌注（HAI）氟脲苷（FUDR）联合全身化疗治疗不可切除老年结直肠癌肝转移患者的疗效及安全性.方法 对18例不可手术切除的老年结直肠癌肝转移回顾性分析.所有患者采用一种改进的介入方法植入肝动脉药盒,术后第2天开始接受HAI FUDR联合全身化疗.对治疗疗效、毒副反应及随访结果进行分析.结果 18例患者的总有效率为94.4%,其中完全缓解1例（5.6%）,部分缓解16例（88.9%）,疾病进展1例（5.6%）.8例患者转化为可手术切除,转化率为44.4%.中位无进展生存时间为26.0个月,中位总生存时间为30.2个月.结论 HAI FUDR联合全身化疗是治疗不可切除老年结直肠癌肝转移的一种安全有效的方法,可获得较高的手术切除率.     

Hepatic artery infusion in the treatment of colorectal cancer metastases

The most common site of metastasis from colorectal carcinoma is the liver. Surgical resection of hepatic metastases can result in long-term survival. The majority of patients have unresectable disease, however, and even if hepatic metastases are resected, most patients will still experience relapse, often in the liver. Hepatic arterial infusion (HAI) of chemotherapy allows high concentrations of a drug to be delivered directly to hepatic metastases with minimal systemic toxicity. HAI therapy has been used to treat unresectable isolated hepatic metastases of colorectal cancer and has also been investigated as adjuvant therapy after resection. This review examines the role of HAI as therapy for both unresectable and resectable hepatic metastases.     

Global approach to hepatic metastases from colorectal cancer: indication and outcome of intra-arterial chemotherapy and other hepatic-directed treatments

Liver metastases of colorectal cancer is present in more than 20% of new diagnosed patients and in 40–60% of relapsed patients. It is a life-threatening prognostic aspect. Hepatic resection, when possible, is the best therapeutic modality, although the overall survival rate is still low (30%). Angiography and intraoperative ultrasonography are useful for resection. The number of hepatic metastases and the surgical margin are probably the most significant prognostic factors. Colorectal cancer may spread predominantly to the liver making regional treatment strategies viable options. Subtotal hepatic resections and segmentectomies are potentially curable procedures for single or small numbers of hepatic metastases without other sites of disease. However, there have been no prospective randomized trials comparing patients with unresected liver metastases and resected metastases. Regional chemotherapy with floxuridine seems usefull combined with hepatic resection or as palliative therapy. Gastric ulcer and biliary sclerosis are the main related toxicities. Patients with localized, unresectable hepatic metastases or concomitant bad medical condition may be candidates for radiation, percutaneous ethanol injection, cryosurgery, percutaneous radiofrequency, hypoxic flow-stop perfusions with bioreductive alkylating agents, hepatic arterial ligation, embolization and chemoembolization. These new hepatic-directed modalities of treatment are being investigated and may offer new approaches to providing palliation and prolonging survival. This review will report the possibilities of intra-arterial chemotherapy and other novel hepatic-directed approaches to the treatment of liver metastases from colorectal cancer.     

Survival following self-administered chemotherapy for liver metastases

Fifty-three patients with unresectable liver metastases from colorectal cancer either self-administered or had a family member administer 5-fluorouracil (5-FU) (12 mg/kg/day for 5 days in alternate weeks) through intraoperatively placed hepatic artery and/or portal vein catheters. Twenty percent had failed previous systemic chemotherapy. Seventeen who were symptomatic received additional radiotherapy. Metastasis was confined to the liver in 38, while 15 also had extrahepatic metastases. Median survival for those with hepatic metastases only was 21 months from diagnosis and 16 months from catheter insertion. There are three long-term survivors in this group, alive 58, 69, and 86 months, respectively, from diagnosis. Median survival for those with hepatic and extrahepatic metastases was 10 months from diagnosis and 6 months from catheter insertion. No patient in this group has survived long term. Catheter-related complications occurred in 20% of the patients; none were fatal. Drug toxicities were minor. Self-administered chemotherapy is a safe, effective, and simple method of achieving prolonged survival in patients with unresectable hepatic metastasis from colorectal cancer.     

Diagnostic evaluation and survival analysis of colorectal cancer patients with liver metastases

Clinical features and their prognostic value were evaluated in 83 colorectal cancer patients with liver metastasis. The clinical features analysed included presenting symptoms and signs, liver function tests, extent of liver involvement, associated extrahepatic tumor growth, and physical condition of the patients. Overall median survival time after diagnosis of liver metastases was 8.4 months. Prognostic factors related to survival were symptoms, when referable to liver metastasis, and 5' Nt. Information is supplied to survey what selection of patients should be considered for various treatment options. A predominance of the patients showed bilobar liver involvement (79.6%), extrahepatic tumor growth (49.4%), or had an unresectable primary tumor (30.1%), thus leaving only 6% of the patients with liver metastases for surgical treatment with the intention of cure.     

Is unexpected peritoneal carcinomatosis still a contraindication for resection of colorectal liver metastases?: Combined resection of colorectal liver metastases with peritoneal deposits discovered intra-operatively

Aims

The discovery of unexpected peritoneal carcinomatosis (PC) at the time of hepatectomy for colorectal liver metastases (CLM) is usually considered a contraindication for continuing resection. The first aim of this study was to assess the long-term outcome of patients operated for CLM, and who presented unexpected PC during laparotomy. The second aim was to identify preoperative predictors of PC.

Methods

All patients at a single center between 1985 and 2010 who had unexpected PC, discovered during planed resection of CLM, and negative preoperative imaging for PC were selected. Clinicopathological data were retrospectively analyzed to assess survival outcomes and to identify predictors of unexpected PC.

Results

Out of the 1340 operated patients for CLM, 42 (3%) had unexpected PC. Only patients (n = 30; 71%) who had PC limited to two abdominal regions (Median peritoneal cancer index (PCI): 2 (1–6)) were resected. Twelve patients were not resected due to the extent of peritoneal disease. The overall survival of the 30 patients resected for CLM who had limited PC was 18% at 5 years (median: 42 months). On multivariate analysis, a previous history of PC, a pT4 stage and bilobar CLM were independent predictors of unexpected PC.

Conclusion

Unexpected PC should not be a contraindication for resection provided that the PCI is low and complete resection of all peritoneal and hepatic lesions can be achieved. Previous history of PC, a pT4 primary tumor and bilobar CLM are associated with increased risk of unexpected PC.     

FDG-PET-CT is effective in selecting patients with poor long term survivals for colorectal liver metastases

Aims

Having incorporated PET-CT as part of the staging process for colorectal liver metastases (CRLM) in our unit since 2008, this study aims to evaluate the survival outcomes of all patients managed by our specialist multi-disciplinary team (MDT).

Methods

All patients with colorectal liver metastases referred to a single liver MDT between 2008 and 2011 were examined. Overall survival (OS) for palliative groups due to occult extrahepatic disease detected by PET-CT (A) and those upfront palliative patients with extensive multi-site disease as identified on baseline CT or disease progression during chemotherapy (B), and resected (C) groups were evaluated and compared. Different extents of occult extrahepatic disease as characterised by PET-CT were also compared.

Results

532 patients were included in the study. Median OS for group A (n = 80), B (n = 161) and C (n = 291) were 10.9, 12.0 and 46.7 months, with a 5-year OS approaching 6.5%, 6.1% and 43.0% respectively. There were significant differences in OS of C vs. A & B (p < 0.001). Single compartment metastases had a significant better survival outcomes than non-torso metastases (p = 0.04).

Conclusion

This is the first report of OS of patients with CRLM excluded from surgery on the basis of PET-CT. We have confirmed that PET-CT is effective in selecting patients with occult extrahepatic disease, which has poor survival outcomes. However, a subgroup with single compartment extrahepatic disease has a better than expected outcome.     

Two-stage hepatectomy combined with converting chemotherapy achieved a successful treatment for initially unresectable multiple bilobar colorectal liver metastases

A 60-year-old man having metachronous multiple bilobar colorectal liver metastases was referred to our institution. The lesions were diagnosed unresectable due to a lack of the estimated future remnant liver volume. He underwent 13 courses of mFOLFOX6 + bevacizumab as down-staging chemotherapy. The periodic abdominal CT scans revealed metastatic lesions to become PR. We had decided to perform two-stage hepatectomy to preserve a hepatic functional reserve. After the rest of chemotherapy for 4 weeks, four tumors were resected and right branch of the portal vein embolization was performed at the first operation. Right hemihepatectomy was performed 5 weeks after the first operation to achieve curative resection. Postoperative course was uneventful and the patient was discharged at 17 days after the operation. He has no signs of tumor recurrence during the follow-up. The combination of two-stage hepatectomy and neoadjuvant systemic chemotherapy may contribute to improve prognoses of initially unresectable multiple bilobar colorectal liver metastases, leading to prolonged survival.     

Lymphatic dissemination of hepatic metastases. Implications for the follow-up and treatment of patients with colorectal cancer

Hepatic spread of colorectal cancer is a prominent cause of treatment failure, but selected patients with liver metastases may attain long-term palliation or cure with liver resection. A review of the records of 81 patients seen at the National Cancer Institute for treatment of colorectal hepatic metastases revealed 7 instances of metastases discovered at operation within the hepatic lymphatic drainage in the absence of other extrahepatic tumor. These patients were studied with reference to location and stage of the primary colon cancer and location of metastases at the time of planned liver resection. All seven patients had their extrahepatic lymphatic disease limited to nodes draining the liver, implicating lymphatic dissemination from hepatic metastases as the mechanism of tumor spread. This pattern of spread rendered these patients unresectable for cure. If lymphatic metastases occur from hepatic tumor this implies a need for frequent and thorough follow-up of patients following resection of a primary colon cancer, and indicates urgency in treatment of liver metastases.     

Cost-effectiveness of laparoscopy versus laparotomy for initial surgical evaluation and treatment of potentially resectable hepatic colorectal metastases: a decision analysis

BACKGROUND AND OBJECTIVES: Approximately 10-40% of colorectal cancer patients with potentially resectable hepatic metastases are incorrectly deemed resectable on standard pre-operative evaluation, including contrast-enhanced CT. Laparoscopy can identify unresectability in a majority of patients at highest risk of being incorrectly deemed resectable, sparing them an unnecessary laparotomy. However, laparoscopy requires an added investment by surgeons, patients, and payers. This analysis seeks to ascertain whether that investment is cost-effective. METHODS: A decision tree model was developed to evaluate the societal cost-effectiveness of laparoscopy versus laparotomy in colorectal cancer patients with hepatic metastases deemed resectable on standard pre-operative evaluation. This comparison involved the cost, the effectiveness, and the incremental cost-effectiveness (the cost in dollars for each quality-adjusted life-year saved) of each option. Sensitivity analysis was performed to evaluate the model's validity under a variety of assumptions. RESULTS: The cost-effectiveness of performing laparoscopy prior to laparotomy for resection of colorectal hepatic metastases depends primarily upon the probability of resectability determined at laparoscopy, and on the sensitivity of diagnostic laparoscopy. CONCLUSION: Laparoscopy for initial evaluation of resectability of hepatic metastases from colorectal cancer is most likely to benefit patients and save costs when performed after pre-operative risk stratification in patients at high risk of radiographically occult unresectable disease.     

Repeated resections for originally unresectable liver metastasis from colorectal cancer after multiagent chemotherapy

We describe the case of a 74-year-old man with liver resection for originally unresectable liver metastasis from colorectal cancer after multiagent chemotherapy. Eleven bilobar liver metastases appeared four months after curative resection for double cancer of sigmoid colon and upper rectum. After 6 courses of multiagent chemotherapy (mFOLFOX 6 with bevacizumab), the number of liver metastasis decreased from 11 to 5. The patient underwent curative resection for liver metastasis. A new lesion of 7 mm in the segment 6 appeared 8 months after an initial liver resection. After 3 months' observation, two more liver metastases appeared. All liver metastases were resected. Solitary lung metastasis appeared 10 months after the second liver resection. The lung metastasis was also resected. The patient was alive with no evidence of disease in 33 months after the initial liver resection. We experienced the case with repeated liver resections after multiagent chemotherapy for originally unresectable bilobar liver metastasis. The therapeutic strategy which combines surgical resection with cytotoxic chemotherapy will be important more than ever.     

立体定向放疗联合或不联合经导管动脉化疗栓塞治疗不可切除结直肠癌肝转移的回顾性研究

目的:比较单纯立体定向放疗或经导管动脉栓塞化疗联合立体定向放疗治疗不可手术结直肠癌肝转移的疗效及安全性。 方法:回顾性分析23例不可手术结直肠癌肝转移患者资料,所有患者曾接受一线标准的全身化疗,化疗后肝脏病灶接受或者经导管动脉栓塞化疗。单纯接受立体定向治疗的13例患者为SBRT组,接受经导管动脉栓塞化疗和立体定向放疗的10例患者为TACE-SBRT组,比较两组患者的肝内病灶局部治疗后的疾病缓解率(RR)、疾病控制率(DCR)和疾病进展时间（TTP）,同时观察并发症发生情况,采用Kaplan-Meier、Log-rank检验,Cox回归模型分析中位无进展生存时间(mPFS)和总生存时间(mOS)。结果:SBRT组和TACE-SBRT组的局部治疗反应RR和DCR无统计学意义（P=0.685）;与SBRT组相比,TACE-SBRT组的无疾病进展时间延长,差异有统计学意义（11.77±1.56 vs 25.40±5.81,P=0.019）。TACE-SBRT的mPFS优于SBRT组,分别为17.4个月和15.1个月（P<0.05）,但是mOS两组之间无统计学意义。同时,仅有1例患者出现Ⅲ级肝功能损伤,治疗后恢复。Cox 回归比例风险模型分析确诊肝转移时CEA水平和同时性转移是无进展生存期和总生存期的预后不良因素(P<0.05)。结论:全身化疗后联合SBRT和TACE治疗不可切除的结直肠癌肝转移是一种安全有效的方法,是一种可接受的替代治疗方法,但仍需进一步研究。     

Repeat hepatectomy for colorectal liver metastases: A worthwhile operation?

BACKGROUND AND OBJECTIVES: After curative resection of hepatic colorectal metastases, 10-20% of patients experience a resectable hepatic recurrence. We wanted to assess the expected risk-to-benefit ratio in comparison to first hepatectomy and to determine the prognostic factors associated with survival. METHODS: Twenty-nine patients from a group of 152 patients resected for colorectal liver metastases underwent 32 repeat hepatectomies. RESULTS: In-hospital mortality was 3.5% (1/29 patients); the morbidity after repeat hepatectomy was lower than that after first hepatic resection. Combined extrahepatic surgery was performed on 34.5% of repeat hepatectomies vs. 6.9% of first hepatectomies (P = 0.01). Overall actuarial 3-year survival was 35.1%: four patients have survived more than 3 years and one survived for more than 5 years. The number of hepatic metastases and the carcinoembryonic antigen (CEA) serum levels were significant prognostic factors on univariate analysis. The synchronous resection of hepatic and extrahepatic disease was not associated with a lower survival rate when compared with that of patients without extrahepatic localization: three patients of the former group are alive and disease-free at more than 2 years. CONCLUSIONS: Repeat hepatic resection can provide long-term survival rates similar to those of first liver resection, with comparable mortality and morbidity. The presence of resectable extrahepatic disease must not be an absolute contraindication to synchronous hepatectomy because long-term survival is possible.     

Curable metastatic colorectal cancer: Recommended paradigms

“Cure” for patients with stage IV colorectal cancer remains elusive, but for a growing subset of patients with colorectal liver metastases (CLMs), cure (ie, > 10-year survival without evidence of disease) is achieved in at least 17% of resected patients. Candidates for resection include those with limited and in some cases extensive hepatic disease, and in highly selected cases, patients with extrahepatic disease. Number, size, and bilaterality of CLMs no longer stand as absolute contraindications to surgery. Chemotherapy has further advanced the field of surgery for CLMs, enabling an additional group of patients who present with unresectable disease to undergo surgery after downsizing with chemotherapy. Modern surgical techniques and liver preparation allow resection after chemotherapy, with excellent results. This article summarizes the current multidisciplinary approach to treatment of CLMs. The definition of resectability, conversion of unresectable CLMs to resectable ones, advances in surgical techniques, advances in chemotherapy, and predictors of outcome are detailed     

大肠癌伴肝转移患者的预后因素

目的探讨影响大肠癌伴肝转移患者预后的因素.方法1995年5月-1999年12月间本院外科手术治疗的64例大肠癌伴肝转移患者,部分患者全身化疗或肝动脉插管化疗,并对其临床资料进行统计分析.结果本组大肠癌肝转移患者占大肠癌患者10.2%.肝转移灶大小、术前CEA水平、原发灶切除、辅助治疗方式为影响生存的独立的预后因素.年龄、性别、肿瘤部位、分化程度、肝转移灶数目与预后无关.肝转移灶＞5cm、术前CEA＞100μg/ml、原发灶未切除的患者的生存时间(3.52月)显著低于其他患者(21.60月).结论治疗方式对肠癌肝转移患者预后影响显著,应积极切除原发灶、治疗转移灶.肝动脉插管化疗优于全身化疗.肝转移灶大小、术前CEA水平是重要的预后指标.     

Preoperative and intraoperative approaches to improve resectability of hepatic colorectal metastases

Given recent improvements in surgical technique and the development of more effective systemic therapies, the indications for surgical resection of colorectal liver metastases are expanding. The major limitation to the complete resection of colorectal liver metastases in the majority of patients, who present with bilobar or bulky disease, is the need to preserve a sufficient functional liver remnant. Strategies to increase the proportion of patients who are candidates for curative resection have emerged over the past several years, including neoadjuvant chemotherapy, portal vein embolization, staged and repeat hepatectomies, minimal-margin resections, ablative techniques, and the systematic resection of extrahepatic disease. The goal of all of these strategies is to permit a complete resection of all metastatic disease while preserving sufficient functional hepatic parenchyma. In this article, we review these novel strategies and discuss their impact on the increasingly complex and evolving multimodality treatment of patients with colorectal liver metastases.     

Liver transplantation for symptomatic liver metastases of neuroendocrine tumours

Numerous reports have demonstrated that liver transplantation for neuroendocrine tumour metastasis is feasible. However, perioperative risks and long-term recurrences remain significant concerns. When liver transplantation is combined with extensive intestinal or pancreatic resection, the risk is particularly high.We report our institutional experience of liver transplantations performed for liver metastases secondary to neuroendocrine tumours, and in combination with a review of the literature, we propose a set of selection criteria. The key points include unresectable hepatic metastases of neuroendocrine origin, absence of extrahepatic metastases, symptomatic disease that is refractory to medical therapy, a Ki-67 level less than 2%, previous resection of the primary disease, and previous therapy for metastatic neuroendocrine tumour.In our experience, the patient in the first case had, post-transplantation, rapid disease progression because of an unidentified primary, and patient in the second case had primary non-function of the liver graft, requiring urgent re-transplantation. More recently, two liver transplantations were successfully performed. The indications were, in the first case, refractory hormonal secretion and, in the other, secondary biliary cirrhosis attributable to hepatic artery therapy with tumour in situ. Subclinical and stable recurrent disease has been detected by scintigraphy in the mesentery and lumbar spine in the former patient. A mesenteric recurrence developed in the latter patient 2 years post transplantation and was subsequently completely resected. At 4 and 5 years post transplantation, both patients are symptom-free.Recurrence after transplantation remains a significant concern, even with careful patient selection, but recurrences may remain indolent. If recurrences are progressive, they may still be amenable to additional medical or surgical therapy. A national or international consensus between oncologists and transplant specialists regarding the indications for liver transplantation is vital, because future progress will depend on careful patient selection and prospective study.     

220例结直肠癌同时肝转移患者临床预后分析

背景与目的:结直肠癌是国内常见的肿瘤之一,结直肠癌同时肝转移的发生率可高达10%～25%。本文探讨影响结直肠癌同时肝转移患者预后的因素和治疗的选择。方法:回顾性分析1995年12月至2002年12月中山大学肿瘤防治中心收治的初治结直肠癌同时肝转移患者220例,对其临床资料进行统计分析。用Kaplan-Meier法对结直肠癌同时肝转移患者的预后进行单因素分析,用Cox模型进行多因素分析。结果:本组病例5年生存率为5.52%,中位生存时间为12.93个月。用Kaplan-Meier及log-rank法对临床特征进行单因素生存分析,有统计学意义的变量因素包括:肝转移灶数目、肝转移灶最大径、肝转移灶分布、肝外是否存在侵犯或转移、确诊时CEA水平、局部区域淋巴结有无转移、病理类型。对临床治疗方式进行单因素生存分析,有统计学意义的变量因素包括:治疗方式、原发灶是否完全切除和化疗方案的选择。用Cox模型进行多因素分析后发现:肝转移灶分布肝叶数、肝转移灶最大径、肝外是否存在侵犯或转移、确诊时CEA水平、治疗模式、原发病灶是否切除、化疗方案为独立的预后危险因素。结论:对于结直肠癌同时肝转移的患者,肝转移灶最大直径超过5cm、肝转移灶分布超过一叶、存在肝外侵犯或转移灶和CEA水平超过200μg/L提示患者预后不良。对于仅有肝转移的结直肠癌患者应尽可能手术根治原发灶以及转移灶,对于手术不能切除的肝转移灶可考虑行全身化疗和/或介入治疗,全身化疗最好选用含草酸铂的方案。