Optimizing the approach to patients with potentially resectable liver metastases from colorectal cancer

Liver metastases are a common event in colorectal carcinoma. Significant advances have been made in managing these patients in the last decade, including improvements in staging and surgical techniques, an increasing armamentarium of chemotherapeutics and multiple local ablative techniques. While combination chemotherapy significantly improves median patient survival, surgical resection provides the only prospect of cure and is the focus of this review. Interpretation of published work in this field is challenging, particularly as there is no consensus to what is resectable disease. Of particular interest recently has been the use of neoadjuvant treatment for downstaging and downsizing disease in patients with initially unresectable liver metastases, in the hope of response leading to potentially curative surgery. This review summarizes the recent developments and consensus guidelines in the areas of staging, chemotherapy, local ablative techniques, radiation therapy and surgery, emphasizing the multidisciplinary approach to this disease and ongoing controversies in this field and examines the changing paradigms in the management of colorectal hepatic metastases.     

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.     

Strategies to increase the resectability of liver metastases from colorectal cancer

Liver resection can provide long-term survival and cure for patients with colorectal liver metastases but is feasible in only 15-25% of patients. In the last few years several major developments have contributed to increase this resectability rate. Neo-adjuvant chemotherapy can provide response rates as high as 50%, allowing surgery in about 10-15% of patients initially deemed unresectable. Patients requiring extensive liver resections with an anticipated small residual liver volume can undergo portal vein embolization to reduce the risk of postoperative liver failure by inducing hypertrophy of the remnant liver. Extensive bilobar disease can be treated by two-stage hepatectomy, with an interval to allow liver regeneration. Ablation techniques can be combined with hepatic resection to reduce local recurrence from incomplete surgical resection margins or to destroy contralateral tumor deposits. Finally, for patients with tumors involving the inferior vena cava or the hepatic veins, in which conventional resection is not feasible, in situ hypothermia or bench resection with reimplantation are suitable for very selected patients. Downstaging strategies may increase the resectability rate of colorectal liver metastases by over 20%.     

结直肠癌肝转移的外科治疗

外科手术是治疗结直肠癌肝转移的重要手段。手术切除的适应证已扩展至满足肝内肿瘤能全部切除、切缘阴性、肝脏储备功能足够即可;而手术切除联合局部治疗进一步扩大了手术适应证。转移癌及原发癌一期或二期手术的远期生存率比较,差异无统计学意义。腹腔镜手术治疗结直肠癌肝转移安全可行,疗效确切。围手术期辅助化疗疗效并不明确,新辅助化疗可能不会使所有患者都受益。     

Quality of life after surgical treatment of colorectal liver metastases

BACKGROUND: The surgical approach to colorectal liver metastases is becoming increasingly aggressive. The aim of this prospective study was to evaluate the impact of surgery on health-related quality of life (HRQoL) of patients with colorectal liver metastases. METHODS: HRQoL data from 97 patients with colorectal liver metastases were analysed. Sixty patients (group 1) had surgical treatment of the liver metastases. Seventeen patients (group 2) were shown to have inoperable disease at laparotomy. Twenty outpatients with inoperable disease were included as a control group (group 3). Two validated HRQoL instruments, the European Organization for Research and Treatment of Cancer Core questionnaire (QLQ C-30) and the EuroQol-5D, were applied. RESULTS: By 2 weeks after operation patients in group 1 showed a clear overall deterioration in HRQoL, but after 3 months most HRQoL scores had returned to baseline levels. At 2 weeks after surgery there was clear deterioration in almost all HRQoL domains in group 2, and several symptoms were still being reported at 3 months. Patients in group 3 showed hardly any deterioration in HRQoL over the 3 months. CONCLUSION: The fast recovery of HRQoL, generally within 3 months, justifies an aggressive surgical approach to colorectal liver metastases. However, careful preoperative evaluation is crucial to avoid needless laparotomy, considering the ongoing deteriorated HRQoL of group 2.     

Shifting concepts in the management of colorectal liver metastases

Management of patients with colorectal liver metastases has evolved considerably due to a better understanding of the biology of the disease with concurrent improvements in surgical techniques, oncological strategies and radiological interventions. This review article examines the factors that have contributed to this radical change. Management will be discussed in relation to chemotherapy, surgery and interventional radiology. The addition of chemotherapy and biological agents has greatly extended the reach and scope of surgery. Parenchymal sparing resections, repeat resections, two stage hepatectomy and Associating Liver Partition and Portal Vein ligation are all available to the hepatobiliary surgeon who deals with colorectal liver metastases. Interventional radiology techniques like liver venous deprivation may also replace established surgical practice. Whilst traditionally it was thought that only a few liver metastases could be treated effectively, nowadays tumour number is no longer a limiting factor provided enough functioning liver can be spared and the patient can tolerate the operation.     

Neoadjuvant chemotherapy as a treatment strategy for multiple bilobar liver metastases from colorectal carcinoma

Hepatic resection remains the only potentially curative therapy for patients with colorectal liver metastases. Because most have multiple bilobar liver metastases, surgical resection is possible in only 25-58% of patients with colorectal liver metastases. Currently, attention is focused on the potential for neoadjuvant chemotherapy to render formerly unresectable patients resectable. The availability of more efficacious chemotherapy agents and an inventive approach to delivery schedules have resulted in an increase in the number of candidates for hepatic resection after neoadjuvant chemotherapy. Although tumor response varies with regimen and/or route of chemotherapy for colorectal liver metastases, with 16-63% tumor response rates, hepatic resection for responders after neoadjuvant chemotherapy gives survival benefits, with 20-48% 5-year survival rates after surgery. Provided that neoadjuvant chemotherapy controls multiple bilobar liver metastases well, aggressive hepatic resection should be considered for patients with those lesions. As a treatment strategy for multiple bilobar liver metastases, neoadjuvant chemotherapy is a useful to increase resection rates and may contribute to the improvement of prognosis in patients with such lesions.     

Surgical treatment of colorectal liver metastasis in the year 2000

There is significant recent progress in the surgical and oncological treatment of colorectal liver metastases. In our review we try to explain the variability and the multidisciplinarity approach we use to treat our patients more successful after the year of 2000. Beside the old rule: "Resect if possible"--thanks to the improvement of chemotherapy and new surgical instruments- there are new trends: "Make it resectable" or "resect it as many times as possible" thanks to the loco-regional and systemic neoadjuvant chemotherapy and/or the repeated interventions in metastasis surgery. The most important prognostic factors influencing the overall survival rate are free surgical margins, synchronous or metachronous metastasis and the need for repeated interventions. The view about extra hepatic metastases of CRC is changed in the last decade as the resection of these metastases is also suggested. After the year 2000 colorectal liver metastases should be treated "a-la-carte", based on multidisciplinary planning and treatment in specialised centres providing the long survival rates.     

Surgical treatment of colorectal liver metastases

Recent advances not only in diagnostic imaging examinations but also in surgical techniques of liver resection have extended the indication of liver resection for colorectal metastases, and accumulated experience has improved surgical outcome. Liver metastases develop in a quarter of patients with colorectal cancer, and of these 30 % are candidates for liver resection under the criteria that liver resection is indicated when all tumors can be removed technically with adequate normal parenchyma left, no extrahepatic metastases are detectable, and the patients is considered fit for surgery. As the 5 year survival rate ranges from 30 % and 40 %, liver resection benefits 9 % to 12 % of patients with liver metastases. Recurrence in the liver remnant after liver resection develops in 40% to 50 %, and repeat liver resection benefits those patients.     

Surgical prospects for liver metastases

The recent advances in liver surgery have made it possible to perform liver resections in an increasing number of patients with consequent improvement in the results. This coincides with an amplification of the indications to liver surgery for metastases. Besides the development of radiological procedures as applied to liver surgery and more effective chemotherapy protocols, the actual approach to patients with liver metastases is shared by three figures - the surgeon, the radiologist and the oncologist. Currently it has been shown that liver resections for metastases are possible with a meaningful increase of survival in the case of colorectal and neuroendocrine liver metastases and in selected cases of non-colorectal non-neuroendocrine metastases. From the technical point of view the most remarkable aspect is the possibility of expanding the criteria of resectability by means of liver resections in one or two steps associated with portal vein embolisation or ligation of a portal branch. It is also possible to perform iterative liver resections and liver transplantation in selected cases of neuroendocrine liver metastases.     

Surgery for colorectal cancer

Colorectal cancer surgery represents a major component of the colorectal service workload. A solid understanding of key anatomical and oncological principles is essential for safe practice. In this article we discuss these fundamental aspects of colorectal cancer surgery. The first part of the article will deal with preoperative staging, surgical planning and principles of oncological surgery. The second part will focus on some of the commonest operations. We will describe key intra-operative principles involved in performing a right hemicolectomy, left hemicolectomy, anterior resection and abdomino-perineal resection. Laparoscopic colorectal cancer surgery is increasingly widespread and therefore our perspective will assume this approach by default. In the final section, we discuss the role of radiotherapy in rectal cancers, transanal surgery, resection of colorectal liver metastases and the rationale behind follow-up.     

Diagnosis and treatment of colorectal liver metastases - workflow

In this review, standards of diagnosis and treatment of colorectal liver metastases are described on the basis of a workshop discussion. Algorithms of care for patients with synchronous / metachronous colorectal liver metastases or locoregional recurrent tumour are presented. Surgical resection is the procedure of choice in the curative treatment of liver metastases. The decision about the resection of liver metastases should consider the following parameters: 1. General operability of the patient (comorbidity); 2. Achievability of an R 0 situation: i. if necessary, in combination with ablative methods, ii. if necessary, neoadjuvant chemotherapy, iii. the ability to eradicate extrahepatic tumour manifestations; 3. Sufficient volume of the liver remaining after resection ("future liver remnant = FLR): i. if necessary, in combination with portal vein embolisation or two-stage hepatectomy; 4. The feasibility to preserve two contiguous hepatic segments with adequate vascular inflow and outflow as well as biliary drainage; 5. Tumour biological aspects ("prognostic variables"); 6. Experience of the surgeon and centre! Extrahepatic disease does not contraindicate hepatectomy for colorectal liver metastases provided a complete resection of both intra- and extrahepatic disease is feasible. Even in bilobar colorectal metastases and 5 or more tumours in the liver, a complete tumour resection has been described. The type of resection (hepatic wedge resection or anatomic resection) does not influence the recurrence rate. Preoperative volumetry is indicated when major hepatic resection is planned. The FLR should be 25 % in patients with normal liver, 40 % in patients who have received intensive chemotherapy or in cases of fatty liver, liver fibrosis or diabetes, and 50-60 % in patients with cirrhosis. In patients with initially unresectable colorectal liver metastases, preoperative chemotherapy enables complete resection in 15-30 % of the cases, whereas the value of neoadjuvant chemotherapy in patients with resectable liver metastases has not been sufficiently supported. In situ ablative procedures (radiofrequency ablation = RFA and laser-induced interstitial thermotherapy = LITT) are local therapy options in selected patients who are not candidates for resection (central recurrent liver metastases, bilobar multiple metastases and high-risk resection or restricted patient operability). Patients with tumours larger than 3 cm have a high local recurrence rate after percutaneous RFA and are not optimal candidates for this procedure. The physician's experience influences the results significantly, both after hepatectomy and after in situ ablation. Therefore, patients with colorectal liver metastases should be treated in centres with experience in liver surgery.     

Treatment for synchronous liver metastasis of colorectal cancer

Colorectal cancer is the second leading cause of cancer death in the developed world, due to formation of distant metastases. The liver is the primary target organ of metastatic lesions, which substantially influence the morbidity of the disease. At the time of diagnosis of colorectal cancer, about 15% to 20% of patients are found to have synchronous liver metastases and an average of 25% of all patients will develop metachronous liver metastases in the course of their disease. Prompt diagnosis of colorectal liver metastases leads to early treatment, which favours a better prognosis. Consequently, the diagnostic process has shifted from traditional clinical procedures to technologically advanced imaging modalities, such as CT, MRI, FDG-PET and PET-CT. The only curative therapy of colorectal liver metastases is surgical resection using the new methods of tissue excision and haemostasis. Depending on the number of metastases, the location, the volume, the extrahepatic spread and the overall condition of the patient, complete resection is only possible in 20% of all cases. If resection is not feasible, a large number of systemic or local palliative treatment options are available.     

Occurrence of synchronous colorectal cancer metastasis in the cirrhotic or fatty liver

AIM: Metastases from colorectal cancers rarely occur in injured livers, however this phenomenon has not been fully investigated in patients with different degree of liver damage. Therefore in this study we evaluated the incidence of synchronous hepatic metastases in patients with fatty or cirrhotic liver submitted to surgery for colorectal neoplasms. METHODS: Seven hundred and forty-seven patients undergoing surgical treatment for colorectal neoplasms were evaluated: the clinicopathological data of 171 patients with liver cirrhosis and 33 with fatty liver were compared to those of 543 patients without liver damage. RESULTS: Gender, age, type of operative procedures performed and histological grading were similar in patients with or without liver damage. In patients with liver cirrhosis the incidence of stage II tumour was greater, while stage IV tumours (P < 0.001) and nodal involvement were significantly lower than in patients with non injured or fatty liver (P < 0.02 and P < 0.001 respectively) . At the time of surgery, synchronous hepatic metastases were present in 32% of patients with normal liver, in 15% of patients with fatty liver (P < 0.02) and in 4.7% of patients with liver cirrhosis (P < 0.001). CONCLUSIONS: Results of our study show that synchronous hepatic metastases of colorectal cancer are less frequently observed in patients with fatty or cirrhotic liver than in patients with non injured liver, indicating that chronically damaged livers are protected from the spread of secondary cancers.     

Surgery for colorectal cancer

Colorectal cancer surgery represents a major component of the colorectal service workload. A solid understanding of key anatomical and oncological principles is essential for safe practice. In this article we discuss these fundamental aspects of colorectal cancer surgery. The first part of the article will deal with preoperative staging, surgical planning and principles of oncological surgery. The second part will focus on some of the most common operations. We will describe key intra-operative principles involved in performing a right hemicolectomy, left hemicolectomy, anterior resection and abdomino-perineal resection. Laparoscopic colorectal cancer surgery is increasingly widespread and therefore our perspective will assume this approach by default. In the final section, we discuss the role of radiotherapy in rectal cancers, transanal surgery, resection of colorectal liver metastases and the rationale behind follow-up.     

Surgery for colorectal cancer

Colorectal cancer surgery represents a major component of the colorectal service workload. A solid understanding of key anatomical and oncological principles is essential for safe practice. In this article we discuss these fundamental aspects of colorectal cancer surgery. The first part of the article will deal with preoperative staging, surgical planning and principles of oncological surgery. The second part will focus on some of the most common operations. We will describe key intra-operative principles involved in performing a right hemicolectomy, left hemicolectomy, anterior resection and abdomino-perineal resection. Laparoscopic colorectal cancer surgery is increasingly widespread and therefore our perspective will assume this approach by default. In the final section, we discuss the role of radiotherapy in rectal cancers, transanal surgery, resection of colorectal liver metastases and the rationale behind follow-up.     

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。     

Treatment of colorectal liver metastases

BACKGROUND: Surgical resection is the only potentially curative treatment for colorectal liver metastases, with 5-year survival rates approaching 40 per cent. However, at present only 20-25 per cent of such lesions are deemed resectable. This review examines developments in neoadjuvant and adjuvant treatments of colorectal liver metastases that aim to improve the results of surgical management of this disease. METHODS: A literature review was undertaken based on a Medline search from 1970 to May 1998. RESULTS: Further evolution in surgical technique is unlikely to lead to a dramatic increase in the resectability rate of colorectal liver metastases. Recent developments in neoadjuvant and adjuvant chemotherapy schedules, together with a range of interventional radiological procedures and interstitial lytic techniques, show promise in terms of extending the limits of resectability and decreasing recurrence rates associated with these lesions. Using multimodality regimens 5-year survival rates of 40 per cent are now being reported for lesions that were initially considered irresectable. CONCLUSION: Patients with colorectal liver metastases should be assessed in units that can offer all the specialist techniques necessary to deliver optimum care. Incorporation of newer neoadjuvant and adjuvant treatments into management strategies should occur in the setting of randomized trials.     

Minimally invasive approach to colorectal surgery

While the development of laparoscopic surgery over the last two decades was amazingly fast, its adoption was neither uniform nor universal. Some procedures, like laparoscopic cholecystectomy, rapidly became the standard of care throughout the surgical community. Laparoscopy for colorectal surgery gained much less acceptance. Factors such as technical complexity, cost, duration of surgery and concerns about oncologic safety influenced the hesitancy in performing this surgery, and it took the surgical community more than a decade to admit that the laparoscopic option is legitimate: it is safe, and it provides the patients with the advantages of minimally invasive surgery, without any surgical or oncologic compromise. This slow process of maturation had a significant advantage, as it allowed this kind of surgery to be thoroughly investigated. Its acceptance is now well based on multitude of data, available from many basic science and clinical studies. Not many procedures in the daily surgical practice are as evidence-based as is laparoscopic colon surgery. The aim of this review was to describe some general aspects of laparoscopic colorectal surgery, and examine the data supporting its use in different procedures for various pathologies, both benign and malignant.     

Two-stage hepatectomy procedure to treat initially unresectable multiple bilobar colorectal liver metastases: technical aspects

A two-stage hepatectomy procedure is a therapeutic strategy for patients presenting with initially unresectable multiple and bilobar colorectal liver metastases in order to achieve a curative R0 resection. The main goal of this approach is to minimize the risk of postoperative liver failure resulting from a too small remnant liver after completing a curative resection. This procedure combines two sequential liver resections that involve perioperative chemotherapy and portal vein embolization. This article describes our standardized strategy of two-stage hepatectomy combined with portal vein embolization used over the last 15 years and discusses the alternative procedures as well as their respective advantages and drawbacks.