The Prophylactic Treatment of Cancer at the Time of Operation

Morales, Francisco; Bell, Millar; McDonald, Gerald O.; Cole, Warren H.

doi:10.1097/00000658-195710000-00006

Cited by 66 publications

(14 citation statements)

References 1 publication

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“…Already in 1957 intraportal injection of cytotoxic agents at the time of surgery for colorectal carcinoma was advocated. 34 The safety of portal vein infusion in man was shown 18 years later,35 in that same year that Taylor et al started a prospective randomized adjuvant cytotoxic liver perfusion study for colorectal carcinoma.' The initial results were encouraging," after a mean follow-up op 26 to 28 months the incidence of liver metastases in the perfusion group (two patients) was significantly lower than in the control group (1 3 patients).…”

Section: Monthsmentioning

confidence: 99%

Adjuvant portal liver infusion in colorectal cancer with 5-fluorouracil/heparin versus urokinase versus control results of a prospective randomized clinical trial (colorectal adenocarcinoma trial I)

Wereldsma

Bruggink

Meijer

et al. 1990

Cancer

102

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This prospectively randomized clinical trial was carried out in four Dutch hospitals to reduce the development of metachronous liver metastases and to get a better survival in patients with colorectal malignancies after surgically radical en bloc resection of the primary tumor and the regional lymph nodes. Three hundred seventeen patients were randomized to participate in three trial arms. One group of patients was treated by surgery alone (control group); in the other patients a catheter was placed in the dilated umbilical vein and advanced until the tip was lying in the left branch of the portal vein. Fifty percent of these patients got immediate postoperative portal infusion with 1 g 5-flnorouracil (5-FU) and 5000 U heparin daily for 7 days; the others received portal vein infusion with urokinase 10.000 U/honr for 24 hours only. Three hundred four patients were eligible. Overall hospital mortality was 3.6% (11 patients) and was not influenced by adjuvant treatment. After a median follow-up of 44 months 66 patients have died with relapse and 21 as a result of other causes. The chance of developing liver metastases and other distant metastases after portal infusion with 5-FU/heparin was one third of the chance in the control group (P < 0.001). Only an insignificant reduction of the average death rate in the 5-FU/heparin group was found.In the urokinase group no significant effect in reducing metastases or in survival was noted. Before recommending cytotoxic portal infusion as an adjuvant treatment in patients with colorectal cancer, detailed analysis of other ongoing portal infusion studies has to be awaited and careful calculations have to be made regarding how many patients really can be saved by this treatment.Cancer 65425-432, 1990.N AUTOPSY STUDIES of patients who died from colo-I rectal cancer, liver metastases were found in about 50% to 80%.' At time of surgery up to 25% of patients with primary colorectal cancer already have macroscopic liver metastases2 The number of patients with microscopic metastases is unknown.Tumor invasion into mesenteric veins causes spread of The authors thank Mrs. Mirjam Linskens for help in data collection and preparation of the manuscript, and Mr. P. J. van Assendelft for assistance in data management and analysis. The authors also thank all of the patients who were willing to cooperate in this study and who had the patience to undergo the multiple sometimes unpleasant investigations.Address for reprints: Jack C. J. Wereldsma, MD, PhD, Department of Surgery, Sint Franciscus Gasthuis, Kleiweg 500,3045 PM Rotterdam, The Netherlands.Accepted for publication July 2 1, 1989.circulating malignant cells to the portal vein.3 These tumor cells surrounded by fibrin and platelets may form tumor clots which can adhere at the vascular endothelium of the liver capillaries. These microfoci can develop into macroscopic metastases initiated by, until now, unknown factors. This tumor cell embolus theory sounds reasonable, the unknown factors being the induction of anesthesia, operative stress...

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Section: Monthsmentioning

confidence: 99%

Adjuvant portal liver infusion in colorectal cancer with 5-fluorouracil/heparin versus urokinase versus control results of a prospective randomized clinical trial (colorectal adenocarcinoma trial I)

Wereldsma

Bruggink

Meijer

et al. 1990

Cancer

102

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“…Metachronous hepatic metastases may develop either from undetectable micrometastases that may already have been established or from the intraportal migration of malignant cells, brought about by the manipulation of the primary tumor at surgery. In an attempt to reduce the subsequent development of hepatic metastases in putatively curable colorectal cancer, adjuvant intraportal chemotherapy was advocated [2] following the demonstration of tumor cells in the venous drainage of resected specimens of carcinoma of the colon [3] and the effectiveness of intraportal administration of nitrogen mustard on the day of injection of cancer cells into the portal vein by significant reduction of liver tumor ''takes'' in rats [4]. Until now, several randomized prospective clinical trials assessing the value of perioperative portal-vein infusion of single [5-fluorouracil (5-FU)] [5][6][7][8] or combination [5-FU and mitomycin C (MMC)] [9,10] of chemotherapeutic agents have been carried out.…”

Section: Introductionmentioning

confidence: 99%

Adverse effects of intraportal chemotherapy on natural killer cell activity in colorectal cancer patients

et al. 1997

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“…As these metastases are mainly fed by portal blood during early growth phases, intraportal chemotherapy would appear to be the most suitable approach for inhibition of lesion proliferation. Non‐randomized studies of intraportal chemotherapy undertaken in the 1950s, using either thiotepa 3 or mechlorethamine, 4 were abandoned because of toxic risk, but subsequent studies of portal vein infusion (PVI) of 5‐FU indicated that this procedure was safe and convenient. The medical community was optimistic, and thousands of patients were entered into clinical trials to evaluate the potential benefit of adjuvant intraportal chemotherapy.…”

Section: Portal Vein Chemotherapymentioning

confidence: 99%

Non‐systemic chemotherapy in the treatment of colorectal cancer—portal vein, hepatic arterial and intraperitoneal approaches

Bruno

Bleiberg

2001

Aliment Pharmacol Ther

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Loco‐regional chemotherapy, an alternative to systemic chemotherapy in the management of colorectal cancer, has been evaluated in both adjuvant and palliative settings. The rationale for loco‐regional delivery is to achieve higher dose concentrations of drugs at the tumour site or at the most common sites of tumour recurrence, while limiting systemic exposure and associated toxicity. Adjuvant intraportal chemotherapy and palliative hepa‐tic arterial chemotherapy have been most extensively investigated. Intraperitoneal chemotherapy has also been studied as an adjuvant treatment after complete resection of colorectal cancer or cytoreductive surgery in patients with established peritoneal carcinomatosis. The results obtained have been disappointing, and none of these procedures can be considered as a standard therapeutic option today. However, methodological difficulties were encountered in most published studies, and the investigated schedules and doses may not have been optimal. New combinations of cytotoxic drugs and new indications are currently under consideration. Promising results have recently been published for adjuvant intraperitoneal chemotherapy and hepatic arterial chemotherapy following surgical resection of hepatic metastases, but additional well‐designed multicentre phase III trials are needed to determine the true benefits of these treatment modalities and to address the issues of cost and quality of life.

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The Prophylactic Treatment of Cancer at the Time of Operation

Cited by 66 publications

References 1 publication

Adjuvant portal liver infusion in colorectal cancer with 5-fluorouracil/heparin versus urokinase versus control results of a prospective randomized clinical trial (colorectal adenocarcinoma trial I)

Adjuvant portal liver infusion in colorectal cancer with 5-fluorouracil/heparin versus urokinase versus control results of a prospective randomized clinical trial (colorectal adenocarcinoma trial I)

Adverse effects of intraportal chemotherapy on natural killer cell activity in colorectal cancer patients

Non‐systemic chemotherapy in the treatment of colorectal cancer—portal vein, hepatic arterial and intraperitoneal approaches

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