A Prospective Randomized Trial of Regional Versus Systemic Continuous 5-Fluorodeoxyuridine Chemotherapy in the Treatment of Colorectal Liver Metastases

Chang, Alfred E.; Schneider, Philip D.; Sugarbaker, Paul H.; Simpson, Craig D.; Culnane, Mary; Steinberg, Seth M.

doi:10.1097/00000658-198712000-00001

Cited by 539 publications

(198 citation statements)

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“…The other explanation pertains to the aggressiveness of the tumor itself, even though biomarkers associated with such a nature of the tumors have not been clarified yet and deserve further investigation. The negative impact of HLN metastasis on survival is in agreement with the report by Chang et al, 22 who demonstrated significantly shorter survival in patients with HLN metastasis (n 5 8) than in patients without HLN metastasis (n 5 18), all of whom were given hepatic arterial chemotherapy. To the best of our knowledge, their report is the only one available discussing the impact of HLN metastasis on the survival of patients with unresectable liver metastasis colorectal cancer.…”

Section: Discussionsupporting

confidence: 91%

Significance of Hepatic Lymph Node Metastasis in Patients With Unresectable Synchronous Liver Metastasis of Colorectal Cancer

Ishida

Ishibashi

Ohsawa

et al. 2011

International Surgery

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The frequency and significance of hepatic lymph node (HLN) metastasis were retrospectively evaluated in 43 patients with unresectable synchronous liver metastasis of colorectal cancer who underwent resection of the primary tumor and histopathologic evaluation of HLNs between March 1997 and August 2007. HLN metastasis was detected in 12 patients (27.9%). No significant correlations were observed between the presence of HLN metastasis and any of the 12 clinicopathologic factors examined. On multivariate analysis using the Cox proportional hazards model, the presence of HLN metastasis (P = 0.002), along with a large number ($4) of regional lymph node metastases (P = 0.003), and nonuse of oxaliplatin-based chemotherapy (P = 0.005) were identified as independent risk factors for shorter survival. To establish a new therapeutic strategy for initially unresectable liver metastasis of colorectal cancer, HLNs should be examined histologically in patients undergoing resection of hepatic lesions when they are rendered resectable by effective chemotherapy.Key words: Hepatic lymph node -Liver metastasis -Colorectal cancer H epatic lymph node (HLN) metastasis, known to be a re-metastasis 1 from liver metastasis in cases of colorectal cancer, is considered to be a poor prognostic factor following potentially curative hepatic metastatectomy. 2,3 Recent advances in effective chemotherapy [4][5][6][7][8] have increased the resection rate of liver metastases of colorectal cancer that are considered unresectable at initial diagnosis. How- ever, little has been reported about the frequency and significance of HLN metastasis in such cases. This retrospective study was performed to examine the status of HLN metastasis in patients with initially unresectable synchronous liver metastasis of colorectal cancer, and to highlight the significance of HLN metastasis in the era of effective chemotherapy. Patients and MethodsThis study was approved by the local ethical committee of Saitama Medical University. PatientsData on 43 patients with unresectable synchronous liver metastasis of colorectal cancer who underwent resection of the primary lesion and histologic examination of HLNs between March 1997 and August 2007 were retrospectively evaluated. In terms of the level of lymph node dissection, along with resection of the primary lesion, D3-level dissection, including removal of pericolic, intermediate, and main lymph nodes, according to the Japanese Classification of Colorectal Carcinoma, 9 was performed in 41 patients, and D2-level dissection, which included removal of the same lymph node groups as above, except the main lymph nodes, was performed in the remaining 2 patients. No patients had peritoneal dissemination, paraaortic lymph node involvement, or distant metastasis other than liver metastasis. During this period, we defined 5 or more hepatic lesions located in both lobes, lesions infiltrating all 3 hepatic veins, and lesions associated with massive infiltration of the inferior vena cava as ''unresectable.'' HLN examinationSystematic ...

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Section: Discussionsupporting

confidence: 91%

Significance of Hepatic Lymph Node Metastasis in Patients With Unresectable Synchronous Liver Metastasis of Colorectal Cancer

Ishida

Ishibashi

Ohsawa

et al. 2011

International Surgery

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“…The remaining five studies (Kemeny M et al, 1986;Chang et al, 1987; Kemeny N et al, 1987;Hohn et al, 1989;Martin et al, 1990) compared intra-arterial therapy with conventional systemic chemotherapy. Overall, 41% of patients receiving intra-arterial treatment responded compared with only 14% of those receiving systemic treatment.…”

Section: Discussionmentioning

confidence: 99%

A phase II study of regional 2-weekly 5-fluorouracil infusion with intravenous folinic acid in the treatment of colorectal liver metastases

Howell

McArdle²,

Kerr³

et al. 1997

Br J Cancer

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Summary Forty patients with unresectable colorectal metastases confined to the liver were evaluated in a phase 11 study. 5-Fluorouracil (5-FU) was delivered via a surgically placed hepatic artery catheter. Patients received folinic acid (200 mg m-2) intravenously over 2 h followed by a loading dose of intra-arterial 5-FU (400 mg m-2) over 15 min, then 5-FU (1600 mg m-2) by intra-arterial infusion over the following 22 h. This was repeated on day 2 and the whole schedule was repeated every 2 weeks. Response was assessed after six treatments. The median follow-up was 17 months. Overall response rate was 46% with 8% complete response. Estimated median survival is 19 months. Site of progression was the liver alone in 55%, liver and lung in another 16% and 29% in other sites. Eight patients experienced grade 3 or 4 toxicity. The response rate of this regimen compares favourably with reported trials of intra-arterial FUDR, and our schedule is currently being compared with a similar schedule of intravenous 5-FU and folinic acid in a randomized Medical Research Council trial (CR05).Keywords: colorectal cancer; liver metastases; chemotherapy; infusion intra-arterial Colorectal cancer is the second most common cause of cancer deaths in the UK. Approximately half of the patients undergoing apparently curative resection will die within 5 years because of recurrent disease, mostly with liver metastases; in 30% of these patients the liver will be the only site affected. Few patients are suitable for surgical treatment, most having multiple metastases affecting both lobes. Unfortunately, the results of conventional systemic chemotherapy have been disappointing. For example, single-agent 5-flourouracil (5-FU) has a response rate of approximately 10% (Blijham et al, 1996). Furthermore, although the addition of folinic acid (FA) to 5-FU has resulted in higher response rates, there remains doubt as to whether this translates into a survival benefit (Advanced Colorectal Cancer Meta-analysis Project, 1992).As most cytotoxic drugs have a steep dose-response curve, it is a basic pharmacokinetic principle that if one can increase drug delivery to a tumour then increased response rates can be achieved (Gamelin et al, 1995). An alternative approach to the therapy of liver metastases is therefore to deliver the drug intra-arterially. In the case of patients with liver metastases the arterial route of delivery is particularly appropriate as it has been shown that established liver metastases over 1 cm in diameter are mainly supplied by the hepatic artery (Breedis, 1954).We report our experience of an intra-arterial 5-FU-based regimen in patients with unresectable colorectal liver metastases. In this study, we combined three factors that, on the basis of pharmacological studies, have been shown to offer a therapeutic advantage, namely intra-arterial administration, infusional rather Received 17 February 1997 Revised 9 April 1997 Accepted 29April 1997 Correspondence to: JD Howell than bolus 5-FU therapy and modulation of 5-FU by high-dose ...

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“…For the vast majority of patients with hepatic metastases, resection is an inappropriate treatment. Chemotherapy administered systemically or regionally to the liver can produce response rates of 17% and 62% respectively (Chang et al, 1987 dearterialisation, embolisation and hepatic artery ligation can produce a limited reponse in selected patient groups at a cost of significant morbidity and no convincing survival benefits (Taylor, 1985;Bengmark, 1989).…”

Section: Discussionmentioning

confidence: 99%

Interstitial laser hyperthermia: a new approach for treating liver metastases

Masters¹,

Steger²,

Lees³

et al. 1992

Br J Cancer

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Summary The palliative management of hepatic metastases remains unsatisfactory. There is a need for a simple non invasive technique which can stop or retard the rate of tumour growth. In principle, Interstitial Laser hyperthermia may fulfil such a role. In experimental studies, this technique produced precise in situ necrosis within solid organs which healed safely. In a pilot feasibility study, we treated ten patients with a total of 18 hepatic metastases on 31 occasions using a percutaneous approach to achieve an overall objective response rate of 44%. The treatment proved simple to perform, was well tolerated and produced radiological evidence of necrosis in small metastases (diameter < 3 cm). However, further research is required before the technique can be regarded as established. Its future role in most cases will be to control the growth of discrete hepatic metastases unsuitable for resection. In instances where the extent of necrosis can be matched accurately to tumour volume, the potential for cure exists.Interstitial Laser Hyperthermia (ILH), an exciting new technique first described in 1983 using the Neodymium: YAG laser (Nd:YAG), is simple both in concept and execution (Bown, 1983). Its basis is the ability to transmit the infra red wavelength of YAG laser light (1064 nm)-an intense energy source, down thin calibre (0.1-0.6 mm) flexible silica or glass fibres with virtually no energy loss. Such small fibre diameters cause negligible tissue damage from their insertion. The light emitting end can be delivered percutaneously into the centre of solid organs (interstitial placement) within the peritoneal cavity using ultrasound guidance with minimal disturbance to the overlying abdominal wall. In contrast to the high powers (50-70 watts) and short exposure times (< 1.0 s) used with the Nd:YAG laser to recanalise obstructing foregut cancers, ILH requires much lower powers (0.5-2.0 watts) with long exposure times (200-1000 s). The laser light is therefore delivered in a more gentle and controlled manner to be absorbed as heat producing a zone of tissue necrosis centred around the fibre tip. The treated area is left in situ to undergo resorption with healing by regeneration and/or fibrosis. In the field of oncology, the prospect of achieving accurate in situ necrosis of malignant tissue simply and atraumatically may obviate, in certain instances, the necessity for surgical excision with its attendant hazards and cost.Experimental work using a single fibre positioned at laparotomy in normal rat liver has produced well defined, reproducible areas of necrosis up to 15 mm in diamter; the diameter being a function of the applied laser power and exposure times (Matthewson et al., 1987). Similar intraoperative studies have also been performed in canine liver using four fibres in juxtaposition fired simultaneously from a single laser (Steger et al., 1988). At 1 week, well defined confluent areas of necrosis up to 3.5 cm in diameter were obtained. These were roughly spherical and centred around the fibres. Such areas...

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A Prospective Randomized Trial of Regional Versus Systemic Continuous 5-Fluorodeoxyuridine Chemotherapy in the Treatment of Colorectal Liver Metastases

Cited by 539 publications

References 19 publications

Significance of Hepatic Lymph Node Metastasis in Patients With Unresectable Synchronous Liver Metastasis of Colorectal Cancer

Significance of Hepatic Lymph Node Metastasis in Patients With Unresectable Synchronous Liver Metastasis of Colorectal Cancer

A phase II study of regional 2-weekly 5-fluorouracil infusion with intravenous folinic acid in the treatment of colorectal liver metastases

Interstitial laser hyperthermia: a new approach for treating liver metastases

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