The blood supply of colorectal liver metastases

Taylor, I.; Bennett, R. Avery; Sherriff, S B

doi:10.1038/bjc.1978.283

Cited by 83 publications

(50 citation statements)

References 18 publications

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“…The majority of treatment modalities are based on the concept that the metastases receive a predominant hepatic arterial supply1'2. However, some tumours obtain a portal vein supply or establish arterioportal anastomoses [3][4][5][6] in order to compensate for arterial loss in treatment targeting the hepatic artery. These observations growth is dependant on angiogenesis, the process by which new capillary blood vessels are generated from preexisting capillaries and venules, induced by growth factors released by the tumour and from those present in the host milieu8-1.…”

Section: Introductionmentioning

confidence: 99%

Microvascular Architecture of Hepatic Metastases in a Mouse Model

1997

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Development of effective treatment for hepatic metastases can be initiated by a better understanding of tumour vasculature and blood supply. This study was designed to characterise the microvascular architecture of hepatic metastases and observe the source of contributory blood supply from the host. Metastases were induced in mice by an intrasplenic injection of colon carcinoma cells (106 cells/ml.) Vascularization of tumours was studied over a three week period by scanning electron microscopy ofmicrovascular corrosion casts. Metastatic liver involvement was observed initially within a week post induction, as areas approximately 100 gm in diameter not perfused by the casting resin. On histology these spaces corresponded to tumour cell aggregates. The following weeks highlighted the angiogenesis phase of these tumours as they received a vascular supply from adjacent hepatic sinusoids. Direct sinusoidal supply of metastases was maintained throughout tumour growth. At the tumour periphery most sinusoids were compressed to form a sheath demarcating the tumour from the hepatic vasculature. No direct supply from the hepatic artery or the portal vein was observed. Dilated vessels termed vascular lakes dominated the complex microvascular architecture of the tumours, most tapering as they traversed towards the periphery. Four vascular branching patterns could be identified as true loops, bifurcations and trifurcations, spirals and capillary networks. The most significant observation in this study was the direct sinusoidal supply of metastases, together with the vascular lakes and the peripheral sinusoidal sheaths of the tumour microculature.

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Section: Introductionmentioning

confidence: 99%

Microvascular Architecture of Hepatic Metastases in a Mouse Model

1997

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“…The disappointing results of regional chemotherapy may be due to the relatively hypovascular nature of hepatic metastases (Taylor et al, 1979), limiting homogeneous drug delivery to the tumour. Indeed the presence of hypovascularised metastases, as defined by radionuclide liver scan with technetium99m-labelled microaggregated albumin, is recognised as a negative prognostic determinant of response in patients receiving hepatic arterial chemotherapy (Rougier et al, 1991).…”

Section: Pharmacological Rationale For Regional Chemotherapymentioning

confidence: 99%

Hepatic arterial chemotherapy for metastatic colorectal carcinoma

Takats

Kerr²,

Poole³

et al. 1994

Br J Cancer

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Summary In this review, the rationale of regional chemotherapy for treatment of hepatic metastases in advanced colorectal carcinoma is discussed. Pharmacokinetic principles and early clinical experience of hepatic arterial drug administration are summarised. The regional advantage of fluoropyrimidine compounds in this setting is well established, and recent evidence suggests that 5-fluorouracil (5-FU) is more efficacious than the analogue 5-fluoro-2'-deoxyuridine (FUDR). However, while significantly higher clinical response rates can be achieved with hepatic arterial infusion (HAI) chemotherapy compared with conventional intravenous drug administration, patient survival benefit is not significantly different. Several novel approaches to overcome the limitations of HAI therapy are currently being explored. These include concomitant use of biodegradable microspheres, which both slow tumour blood flow and enhance tumour drug uptake, and use of vasoactive agents to redistribute arterial blood flow towards tumours. In addition, novel chemotherapeutic agents which exploit unique biological characteristics of hepatic tumours are entering clinical trial.The conventional notion of chemotherapy is of a truly systemic treatment designed to combat widely disseminated malignant disease. Colorectal carcinoma is relatively unresponsive to chemotherapy (Mayer, 1992), despite an increasing understanding of drug mechanisms of action at the molecular level. To date, systemic 5-FU plus folinic acid is considered the optimum treatment for metastatic colorectal cancer, yielding response rates of around 25% and median survival of around 12 months (Piedbois et al., 1992). These disappointing results reflect, in part, the narrow therapeutic ratio of 5-FU and the presence of associated severe systemic side-effects limiting dose escalation. Regional chemotherapy affords an alternative method of cytotoxic drug administration which circumvents the constraints of systemic administration, while introducing the concept of targeted drug delivery to metastatic disease localised to specific components of the body.Three levels of tumour targeting have been described (Widder et al., 1979): (1) selective drug delivery to the tumourbearing organ, (2) drug delivery biased to tumour rather than to normal tissue within that organ and (3) enhancement of uptake of cytotoxic drug by malignant cells. In this context, regional chemotherapy constitutes first-order targeting. Currently, the value of this method of drug delivery is being assessed in a number of different malignancies, but experience is greatest in the treatment of hepatic metastases from colorectal carcinoma.Colorectal carcinoma is the second most common malignancy in the UK and the cause of over 19,000 deaths per year. Epidemiological studies show that the incidence of colorectal carcinoma is increasing, with approximately 28,000 new cases now being diagnosed annually. Up to 50% of patients with colorectal carcinoma develop liver metastases, from which as many as 70% of patients will subsequen...

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“…The rationale of the treatment is that higher concentration of cytotoxic drugs metabolised by the liver can be infused via the hepatic artery and are retained within the organ minimising the systemic side-effects (Ensminger et al, 1978;Sigurdson et al, 1986). Furthermore, because the blood supply of overt hepatic metastases is derived principally from the hepatic artery (Ackerman et al, 1969;Taylor et al, 1979) it was postulated that the tumour should retain more of the cytotoxic drug than normal liver cells.…”

mentioning

confidence: 99%

“…The disappointing results of regional chemotherapy may be related to the relatively hypovascular nature of the majority of liver metastases (Taylor et al, 1979) which limits presentation of the drug to the tumour. Numerous vasoactive drugs have been used to manipulate hepatic blood flow in tumour bearing patients and animals (Sasaki et al, 1985;Burton & Gray, 1987).…”

mentioning

confidence: 99%

The effects of intra-arterial vasoconstrictors on the distribution of a radiolabelled low molecular weight marker in an experimental model of liver tumour

Hemingway

Cooke²,

Chang³

et al. 1991

Br J Cancer

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Regional delivery of angiotensin II and phenylephrine caused significantly greater retention of marker in tumour than liver with an overall 4-fold increased retention of marker one minute after its injection. Ninety minutes after injection there was still significant retention of marker compared to control animals. Regional delivery of hepatic artery vasoconstrictors increase delivery of marker and may increase delivery of chemotherapeutic drug to liver tumour.

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The blood supply of colorectal liver metastases

Cited by 83 publications

References 18 publications

Microvascular Architecture of Hepatic Metastases in a Mouse Model

Microvascular Architecture of Hepatic Metastases in a Mouse Model

Hepatic arterial chemotherapy for metastatic colorectal carcinoma

The effects of intra-arterial vasoconstrictors on the distribution of a radiolabelled low molecular weight marker in an experimental model of liver tumour

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