The incidence of oesophageal adenocarcinoma has risen throughout the Western world over the last three decades. The prognosis remains poor as many patients are elderly and present with advanced disease. Those patients who are suitable for resection remain at high risk of disease recurrence. It is important that cancer patients take part in a follow up protocol to detect disease recurrence, offer psychological support, manage nutritional disorders and facilitate audit of surgical outcomes. Despite the recognition that regular postoperative follow up plays a key role in ongoing care of cancer patients, there is little consensus on the nature of the process. This paper reviews the published literature to determine the optimal timing and type of patient follow up for those after curative oesophageal resection.
SummaryMany colorectal liver metastases are hypovascular, and their low level of perfusion is associated with limited drug uptake and poor response rates with regional chemotherapy. We
Sunnua" Regional chemotherapy. delivered via the hepatic artery. may significantly increase tumour response rates in patients with colorectal liver metastases. However, survival is limited by extrahepatic disease progression. We have developed a novel therapeutic approach for patients with metastases confined to the liver. In order to achieve high local response rates and also inhibit extrahepatic progression. 5-fluorouracil (5-FU) was infused intra-arterially at a dose previously calculated to achieve both high-dose regional therapy and adequate systemic levels. To enhance efficacy further, 5-FU was combined with high-dose systemic folinic acid (FA). Thirty-one patients were evaluated in a phase II study. 5-FU (1.5 g m2) was infused via a surgically implanted hepatic artery catheter over a 24 h period: FA (total 400 mg m-2) was infused intravenously during the initial and final 2 h. Treatments were given weekly for cycles of 6 weeks' duration. To date, median duration of treatment is 6 months and the median follow-up period is 17 months. 1992a) we initiated a phase II study using high-dose IHA 5-FU so that 'spill-over' into the systemic circulation occurred. To enhance efficacy further. we adopted a schedule using prolonged infusions modulated by high-dose systemic folinic acid. Our aims were not only to maximise tumour response rates but also to delay extrahepatic progression in an attempt to prolong survival. Patients and methodsFrom 1 March 1990 to 31 March 1993. 59 patients with colorectal liver metastases were considered for possible inclusion in the study. which had previously been approved by the local ethical committee. Five of these patients had a WHO performance >2 and were not investigated further. The remaining patients underwent CT scanning of abdomen and pelvis and either thoracic computerised tomography (CT) Thirty-one patients [nine female, 22 male. median age 59 years (range 37-77)] were therefore included. Multiple metastases were detected at the time of primary surgery in 24 patients. Three patients had undergone either wedge resection elsewhere (n = 2) or formal hepatic resection (n = 1) for apparently solitary tumours and were included following tumour recurrence. The remaining four patients had metastases diagnosed at follow-up (range 5-15 months post resection of the primary tumour). Six patients had between 25% and 50% of their livers replaced by tumour (assessed by CT image analysis), while the others had less than 25% hepatic replacement. The median number of metastases was 5 (range 1-30). The patient with a solitary tumour had a catheter placed at the time of primary surgery with a view to treating with regional chemotherapy and hepatic resection at a later (D Macmillan Press Ltd
SummaryRegional chemotherapy is an attractive but underevaluated method of treating locally advanced breast cancer. We have combined two novel methods of targetting by delivering a single pulse of adriamycin-loaded albumin microspheres down a radiologically placed internal mammary artery catheter. A complete response was observed and prolonged local control achieved.
Summary Recent clinical trials have suggested that a combination of folinic acid and 5-fluorouracil (5-FU) may improve response rates and survival in patients with advanced colorectal cancer. However, this regimen has been complicated by potentially life threatening toxicity. Regional delivery of folinic acid via a hepatic artery catheter might be expected to reduce systemic exposure and subsequent adverse effects.The present study compared the pharmacokinetic profiles of intravenous and intra-hepatic arterial infusions of folinic acid in patients with colorectal liver metastases (n = 6) who were being treated with weekly regional infusions of 5-FU. The mean area under the plasma concentration -time curve, the peak plasma concentration and the steady state volume of distribution were 163 jig ml-' h-' (SD 41), 18.5 jg ml-' (SD 1.2) and 7.41 m-2 (SD 0.44) respectively following intravenous administration of folinic acid compared with 142jigml-h-' (SD45), 14.8tjgml-' (SD2.4) and 11.21m2 (SD 1.22) following intra-hepatic arterial administration (P <0.05). Regional folinic acid was therefore associated with a statistically significant reduction in systemic exposure compared with the intravenous route.The outlook for patients with colorectal liver metastases remains depressing; the mean survival for patients in the West of Scotland is approximately 3 months (Wood et al., 1976). The results of systemic chemotherapy have been disappointing. Average response rates of only 10-15% have been reported following treatment with 5-FU and response has not been accompanied by increased survival (Kemeny, 1983). These reports have lead to a third of surgeons in England and Wales opting not to actively treat patients with nonresectable colorectal liver metastases (Karanjia et al., 1990) and trials in the UK continue to include 'no active treatment' control arms (Hunt et al., 1990).Recent studies, however, have suggested that the addition of folinic acid may significantly improve survival amongst advanced colorectal cancer patients receiving 5-FU (Erlichman, 1988, Poon et al., 1989Kerr, 1989). Briefly, folinic acid enhances 5-FU activity by stabilising the binding of the 5-FU metabolite, fluorodeoxyuridine monophosphate, to the enzyme thymidylate synthase. Unfortunately, therapy has been complicated by systemic toxicity which can be occasionally life-threatening.The rationale for regional chemotherapy is the delivery of high drug concentrations to the compartment harbouring the tumour with relatively less drug escaping into the systemic vascular compartment. There is a large literature on intrahepatic arterial administration of 5-FU and FUdR to patients with hepatic metastases from colorectal primary cancers. In summary, the data are suggestive that tumour response rates are higher comparing regional with systemic administration, but there is no convincing evidence that intra-arterial chemotherapy significantly prolongs survival.The aim of the present study was to compare the pharmacokinetic profiles of intravenous and intra-hepatic ...
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