Current preventive treatment for recurrence after curative hepatectomy for liver metastases of colorectal carcinoma： A literature review of randomized control trials

To review the preventive approaches for recurrence after curative resection of hepatic metastases from colorectal carcinoma, we have summarized all available publications reporting randomized control trials (RCTs) covered in PubMed. The treatment approaches presented above include adjuvant intrahepatic arterial infusion chemotherapy, systemic chemotherapy, neoadjuvant chemotherapy, and immunotherapy. Although no standard treatment has been established, several approaches present promising results, which are both effective and tolerable in post-hepatectomy patients. Intrahepatic arterial infusion chemotherapy should be regarded as effective and tolerable and it increases overall survival (OS) and disease free survival (DFS) of patients, while 5-fluorouracil-based systemic chemotherapy has not shown any significant survival benefit. Fortunately chemotherapy combined with hepatic arterial infusion and intravenous infusion has shown OS and DFS benefit in many researches. Few neoadjuvant RCT studies have been conducted to evaluate its effect on prolonging survivals although many retrospective studies and case reports are published in which unresectable colorectal liver metastases are downstaged and made resectable with neoadjuvant chemotherapy. Liver resection supplemented with immunotherapy is associated with optimal results; however, it is also questioned by others. In conclusion, several adjuvant approaches have been studied for their efficacy on recurrence after hepatectomy for liver metastases from colorectal cancer (CRC), but multi-centric RCT is still needed for further evaluation on their efficacy and systemic or local toxicities. In addition, new adjuvant treatment should be investigated to provide more effective and tolerable methods for the patients with resectable hepatic metastases from CRC.     

Value and prognostic factors of repeat hepatectomy for recurrent colorectal liver metastasis

Background: More than 50% of patients with colorectal cancer develop liver metastases. Hepatectomy is the preferred treatment for resectable liver metastases. This review provides a perspective on the utility and relevant prognostic factors of repeat hepatectomy in recurrent colorectal liver metastasis(CRLM). Data sources: The keywords “recurrent colorectal liver metastases”, “recurrent hepatic metastases from colorectal cancer”, “liver metastases of colorectal cancer”, “repeat hepatectomy”, “re...     

Short-term effectiveness of radiochemoembolization for selected hepatic metastases with a combination protocol

AIM:To introduce the combination method of radio-chemoembolization for the treatment of selected hepatic metastases. METHODS:Twenty patients with biopsy proven hepatic metastases were selected from those who underwent transarterial radiochemoembolization, a novel combination protocol, between January 2009 and July 2010. Patients had different sources of liver metastasis. The treatment included transarterial administration of three chemotherapeutic drugs (mitomycin, doxorubicin and cisplatin), followed by embolization with large (50-150 μm) radioisotope particles of chromic 32P. Multiphasiccomputer tomography or computer tomography studies, with and without contrast medium injections, were performed for all patients for a short-term period before and after the treatment sessions. The short-term effec-tiveness of this procedure was evaluated by modified response evaluation criteria in solid tumors (mRECIST), which also takes necrosis into account. The subjective percentage of necrosis was also assessed. The response evaluation methods were based on the changes in size, number, and the enhancement patterns of the lesions between the pre-and post-treatment imaging studies. RESULTS:Patients had liver metastasis from colorectal carcinomas, breast cancer, lung cancer and carcinoid tumors. The response rate based on the mRECIST criteria was 5% for complete response, 60% for partial response, 10% for stable disease, and 25% for progressive disease. Regarding the subjective necrosis percentage, 5% of patients had complete response, 50% had partial response, 25% had stable disease, and 20% had progressive disease. Based on traditional RECIST criteria, 3 patients (15%) had partial response, 13 patients (65%) had stable disease, and 4 patients (20%) had disease progression. In most patients, colorectal carcinoma was the source of metastasis (13 patients). Based on the mRECIST criteria, 8 out of these 13 patients had partial responses, while one remained stable, and 5 showed progressive disease. We also had 5 cases of breast cancer metastasis which mostly remained stable (4 cases), with only one partial response after the procedure. Six patients had bilobar involvement; three of them received two courses of radiochemoembolization. The follow up imaging study of these patients was performed after the second ses-sion. In the studied patients there was no evidence of extrahepatic occurrence, including pulmonary radioac-tive deposition, which was proven by Bremsstrahlung scintigraphy performed after the treatment sessions. For the short-term follow-ups for the 2 mo after the therapy, no treatment related death was reported. The mostly common side effect was post-embolizationsyndrome, presented as vomiting, abdominal pain, and fever. Nineteen (95%) patients experienced this syndrome in different severities. Two patient had ascites (with pleural effusion in one patient) not related to hepatic failure. Moreover, no cases of acute liver failure, hepatic infarction, hepatic abscess, biliary necrosis, tumor rupture, surgical cholecystitis, or non-targeted gut embolization were reported. Systemic toxicities such as alopecia, marrow suppression, renal toxicity, or cardiac failure did not occur in our study group. CONCLUSION:Radiochemoembolization is safe and effective for selected hepatic metastases in a short-term follow-up. Further studies are required to show the long-term effects and possible complications of this approach.     

Chemotherapy and resection for gastric cancer with synchronous liver metastases

AIM: To investigate the effect of surgery and chemotherapy for gastric cancer with multiple synchronous liver metastases (GCLM). METHODS: A total of 114 patients were entered in this study, and 20 patients with multiple synchronous liver metastases were eligible. After screening with preoperative chemotherapy, 20 patients underwent curative gastrectomy and hepatectomy for GCLM; 14 underwent major hepatectomy, and the remaining six underwent minor hepatectomy. There were 94 patients without aggressive treatment, and they were in the non-operative group. Two regimens of perioperative chemotherapy were used: S-1 and cisplatin (SP) in 12 patients, and docetaxel, cisplatin and 5-fluorouracil (DCF) in eight patients. These GCLM patients were given preoperative chemotherapy consisting of two courses chemotherapy of SP or DCF regimens. After chemotherapy, gastrectomy and hepatectomy were preformed. Evaluation of patient survival was by follow-up contact using telephone and outpatient records. All patients were assessed every 3 mo during the first year and every 6 mo thereafter. RESULTS: Twenty patients underwent gastrectomy and hepatectomy and completed their perioperative chemotherapy and hepatic arterial infusion before and after surgery. Ninety-four patients had no aggressive treatment of liver metastases because of technical difficulties with resection and severe cardiopulmonary dysfunction. In the surgery group, there was no toxicity greater than grade 3 during the course of chemotherapy. The response rate was 100% according to the Response Evaluation Criteria in Solid Tumors Criteria. For all 114 patients, the overall survival rate was 8.0%, 4.0%, 4.0% and 4.0% at 1, 2, 3 and 4 years, respectively, with a median survival time (MST) of 8.5 mo (range: 0.5-48 mo). For the 20 patients in the surgery group, MST was 22.3 mo (range: 4-48 mo). In the 94 patients without aggressive treatment, MST was 5.5 mo (range: 0.5-21 mo). There was a significant difference between the surgery and unresectable patients (P = 0.000). Thr     

Incidence and treatment of hepatic artery complications after orthotopic liver transplantation

AIM: To investigate the incidence and treatment of hepatic artery complications after orthotopic liver transplantation. METHODS: From February 1999 to May 2002, orthotopic liver transplantations (OLT) were performed in 72 patients with end-stage liver diseases with an average age of 40.2±13.6 years (ranged from 11 to 68 years), 56 were males and 16 females. The preoperative evaluation for the 72 patients was performed using duplexsonography, abdominal CT scan, and angiography of the hepatic artery. All donor grafts were perfused and preserved in University of Wisconsin solution at 4℃. OLT was performed with standard techniques with or without a veno-venous bypass. Reconstructions of hepatic artery were performed between the branch patches of gastroduodenal/hepatic or splenic/common hepatic artery confluence of the donors and recipients, and an end-to-end anastomosis between other arterial vessels of the donors and recipients was done. Arterial anastomosis was performed with interrupted 7-0/8-0 monofilament polypropylene suture under 3.5 x Ioupe magnification. Diagnosis of the complications of hepatic artery after OLT was based on the clinical presentations, ultrasound findings and arterial angiography. All patients were followed up regularly for duplex ultrasound scan after discharge. RESULTS: The overall incidence of arterial complications in 72 patients after OLTs was 1.4% (1/72). One 3cm pseudoaneurysm at the side of anastomotic site of hepatic artery was found by urgent arteriogram due to hemoperitoneum secondary to bile leakage after OLT. Subsequently the pseudoaneurysm was successfully embolized and the blood flow toward the donor liver in hepatic artery remained. The overall postoperative 30day mortality rate was 8.33%. The one-year survival rate was 83.72% in 50 patients with benign diseases and was 71.43% in 22 patients with malignant diseases following OLT. No death associated with complications of hepatic artery occurred. CONCLUSION: Careful preoperative evaluations and intraoperative microsurgical technique for hepatic artery reconstructions are the keys in prevention of hepatic artery complications after OLT.     

Treatment for liver metastases from breast cancer： Results and prognostic factors

AIM: Liver metastases from breast cancer (BCLM) are associated with poor prognosis. Cytotoxic chemotherapy can result in regression of tumor lesions and a decrease in symptoms. Available data, in the literature, also suggest a subgroup of patients may benefit from surgery, but few talked about transcatheter arterial chemoembolization (TACE). We report the results of TACE and systemic chemotherapy for patients with liver metastases from breast cancer and evaluate the prognostic factors. METHODS: Forty-eight patients with liver metastases, from proved breast primary cancer were treated with TACE or systemic chemotherapy between January 1995 and December 2000. Treatment results were assessed according to WHO criteria, along with analysis of prognostic factors for survival using Cox regression model. RESULTS: The median follow-up was 28 mo (1-72 mo). Response rates were calculated for the TACE group and chemotherapy group, being 35.7% and 7.1%, respectively. The difference was significant. The one-, two- and three-year Survival rates for the TACE group were 63.04%, 30.35%, and 13.01%, and those for the systemic chemotherapy group were 33.88%, 11.29%, and 0%. According to univariate analysis, variables significantly associated with survival were the lymph node status of the primary cancer, the clinical stage of liver metastases, the Child-Pugh grade, loss of weight. Other factors such as age, the intervals between the primary to the metastases, the maximal diameter of the liver metastases, the number of liver metastases, extrahepatic metastasis showed no prognostic significances. These factors mentioned above such as the lymph node status of the primary cancer, the clinical stage of liver metastases, the Child-Pugh grade, loss of weight were also independent factors in multivariate analysis. CONCLUSION: TACE treatment of liver metastases from breast cancer may prolong survival in certain patients. This approach offers new promise for the curative treatment of the patients with metastatic breast cancer.     

Angiography for diagnosis and treatment of colorectal cancer

AIM: To evaluate the role of preoperative angiography in the diagnosis and treatment of colorectal cancer.METHODS: The authors performed selective arterial cannulation by Seldinger‘s method in 47 patients to locate the primary cancer and to diagnose metastasis to the liver.Each patient was then given intra-arterial regional chemotherapy, and received 5-fluorouracil (5-Fu, 1000mg),mitomycin C (MMC, 20mg), and cisplatinum (CDDP, 80mg).RESULTS: The location and shape of each tumor were observed, including metastatic tumors in the liver, in 42 of the 47 (89.4%) patients. The site of the primary tumor was difficult to identify in 5 cases because the patients had a recurrence of cancer. Arterial chemotherapy was performed successfully in all patients. The authors recorded no partial or significant morbidity resulted from angiography. The only incident was bleeding from the artery puncture site in one patient, which was successfully stopped by general medication.CONCLUSION: Preoperative selective arterial angiography can help the diagnosis and locate primary tumors and to detect liver metastasis. At the same time, regional arterial chemotherapy can be an important form of preoperative therapy.     

Improving definition of the term “synchronous liver metastases” from colorectal cancer

正The liver is the most frequent site of metastasis in colorectal cancer with up to a quarter of patients having liver metastases at the time of initial diagnosis and a further third subsequently developing liver lesions.~([1])Patients who present with metastatic liver disease after treatment of the primary(termed metachronous disease)receive care focused on this new metastatic disease.~([2])In contrast,the management of patients who present with colorectal cancer and concurrent liver     

Phase Ⅰ clinical study of personalized peptide vaccination combined with radiotherapy for advanced hepatocellular carcinoma

AIM To assess the efficacy and safety of a new treatment modality, cellular immune therapy based on personalized peptide vaccination(PPV-DC-CTL) combined with radiotherapy, for treating advanced hepatocellular carcinoma(HCC). METHODS A total of nine patients with advanced HCC were enrolled. Multidisciplinary consultation confirmed that all the patients definitely had no opportunity of surgery, because four patients had multiple liver metastases(the number of liver lesions 3), one patient had liver metastases and portal vein tumor thrombosis, one patient had lung and bone metastases, two patients had liver and lung metastases and one patient had liver metastasis and peritoneal metastasis. Patients with metastasis were treated with precise radiotherapy combined with PPV-DC-CTL.RESULTS Following radiotherapy and one to three cycles of PPV-DC-CTL treatment, AFP levels were significantly decreased in six patients and imaging assessment of the lesions showed a partial response(PR) in three patients and stable disease in the other three patients. The response rate was 33% and disease control rate was 66%. This regimen was found to be safe and well tolerated. None of the patients developed liver or kidney side effects. Only one patient developed grade Ⅱ bone marrow suppression and the remaining patients had no significant hematological side effects.CONCLUSION Radiotherapy combined with PPV-DC-CTL provides a new therapeutic strategy for patients with advanced HCC, which is well tolerated, safe, feasible and effective.     

Challenges in everyday surgical practice: synchronous bilobar hepatic colorectal metastases--newer multimodality approach

BACKGROUND/AIMS: This study was designed to assess the efficacy of two-stage liver surgery and hepatic directed chemo-biological therapy in treatment of synchronous bilobar hepatic metastases of colorectal origin. METHODOLOGY: A total of thirty-two patients were included in this study that were diagnosed to have colorectal carcinoma with synchronous bilobar hepatic metastases. During stage one surgery along with excision of primary colorectal carcinoma; ligation and transection of main portal branch on side of bulky metastases disease (right branch in 28 and left in 4 patients) was performed. The metastatic nodules in the opposite lobe were ablated by microwave therapy and a hepatic arterial jet port catheter was introduced via the gastroduodenal artery for liver directed chemo-biological therapy. The catheter was connected to a subcutaneously placed port. Three cycles of chemotherapeutic drugs and Avastin (Bevacizumab) were given via hepatic arterial infusion (HAI) at intervals of twenty-five days. During the second stage surgery hepatic resection was carried out followed by continuation of hepatic arterial infusion of chemobiological drugs as adjuvant therapy. RESULTS: In the follow-up period of 31 months, 1-year survival of 100% and 2-year survival of 80% with a mean 28 months survival was noted. CONCLUSIONS: Combined approach of ligating the portal branch, microwave ablation, hepatic regional chemo-biological therapy and staged liver surgery (a multimodality approach) in the treatment of advanced liver metastatic disease synchronous with colorectal cancer is an effective method of treatment which improves the overall survival and quality of life of the patient with hepatic bilobar metastases synchronous with colorectal carcinoma. Avastin, a monoclonal antibody against vascular endothelial growth factor; used for inhibition of tumor growth has shown its efficacy in early results and holds good promise for the future.     

A study of liver metastasis from colorectal cancer in which hepatic resection was performed after hepatic arterial infusion chemotherapy]

We experienced 5 cases of liver metastases from colorectal cancer, in which hepatic resection was carried out after down sizing by hepatic arterial infusion chemotherapy. In addition, a histological study about the effect of chemotherapy on the liver tumor was performed. Primary lesions were located at the sigmoid colon (2), cecum (1), descending colon (1) and rectum (1). We carried out hepatic arterial infusion chemotherapy using mainly 5-FU. The total amount of 5-FU was 10-81 g. Tumor volumes were reduced by 12.5-24%, and they were judged PR. However, surgery was indicated due to obstruction of the proper hepatic artery or other side effects. Postoperative courses were uneventful and the hospital stays were from 17-61 days, and all patients were still alive in tumor-free condition at writing. By the histological study of the excised specimen, we recognized not only remarkable fibrous changes or calcifications but also overt viable cancerous cells. We conclude that the option of hepatic resection after controlling the development of the cancer by hepatic arterial infusion chemotherapy is a rational strategy of treatment for liver metastasis from colorectal cancer.     

Hepatic arterial infusion alternating with systemic chemotherapy in patients with non-resectable hepatic metastases from colorectal cancer

BACKGROUND AND AIM: Hepatic arterial infusion (HAI) chemotherapy has a number of limitations, including a low rate of complete response and frequent extrahepatic recurrence, in colorectal cancer patients with non-resectable hepatic metastases. METHODS: Twenty-nine colorectal cancer patients with non-resectable hepatic metastases were consecutively enrolled for HAI alternating with systemic chemotherapy (HA + SC group). The protocol comprised six cycles of alternating HAI (5-FU + leucovorin for 14 days, and mitomycin C on the first day) and systemic chemotherapy (5-FU + leucovorin). Colorectal cancer patients with two or more hepatic metastases treated using hepatic resection and systemic chemotherapy (HR + SC group) were selected as a comparative group. RESULTS: Within the HA + SC group, complete response was achieved in eight patients (28%), whereas 13 patients (45%) showed progressive disease. Six of the eight patients with complete response lived for more than 38 months. Extrahepatic recurrences were more frequent in the HR + SC group than the HA + SC group (47 vs 21%, P = 0.024). The two groups did not differ with respect to overall and hepatic progression-free survival (P = 0.947 and 0.444, respectively), displaying median +/- SE values of 38 +/- 7 and 20 +/- 3 months in the HA + SC group, and 39 +/- 9 and 33 +/- 14 months in the HR + SC group, respectively. One patient in each group experienced toxic hepatitis, and sclerosing cholangitis occurred in one patient of the HA + SC group. Other complications were mostly grade 1 or 2. CONCLUSIONS: HAI alternating with systemic chemotherapy led to a promising response and hepatic progression-free survival, possibly reducing extrahepatic recurrence in colorectal cancer patients with non-resectable liver metastases.     

Complications of hepatic artery infusion: a review of 4580 reported cases

Purpose: The resurgence of hepatic artery infusion (HAI) for the treatment of colorectal liver metastases has been dampened by concern over its complications. We have reviewed the incidence and frequency of complications associated with HAI and discussed the factors associated with these complications. Methods: A PUBMED search was conducted from 1950–2001 using various combinations of these keywords: hepatic arterial infusion, colorectal carcinoma, complications, and trials. The main inclusion criterion was the reporting of HAI complications. The main exclusion criterion was duplicated patients. Extracted data included chemotherapeutic agents, catheter technique, drug toxicities, and catheter related complications. Relative risks and 95% confidence intervals were calculated. Results: We reviewed 437 articles/abstracts and included 101 studies. 4580 patients with 4582 toxicities and complications were reported. The mortality rate was 1%. The most common toxicities were: GI symptoms 22%, chemical hepatitis 19%, and bone marrow toxicity 8%. 5-fluorouracil (5-FU) HAI had statistically significant risk for GI symptoms and bone marrow toxicity. Floxuridine (FUDR) HAI had statistically significant risk for chemical hepatitis, sclerosing cholangitis, and biliary toxicity. The most common catheter complications were: hepatic artery occlusion 6%, catheter thrombosis 5%, and catheter displacement 7%. Conclusions: This literature review of the complications of HAI confirms a low mortality associated with HAI. Sclerosing cholangitis and chemical hepatitis are associated with the use of FUDR, while the use of 5-FU is associated with bone marrow toxicity. Our observations support the development of hepatic cytoprotective agents and other effective anti-tumor agents to improve the results and morbidity of HAI for colorectal liver metastases.     

Effective retreatment of patients with colorectal cancer and liver metastases

Twenty-two patients with colorectal cancer and metastatic liver disease in whom systemic intravenous therapy with 5-fluorouracil previously had failed were given fluorodeoxyuridine and mitomycin C by hepatic arterial infusion. Ten of the 22 patients (45.4 percent) had a partial response and median survival of 14 months, as opposed to a median survival of six months among the 12 patients who did not have response to the treatment (p = 0.02). Hepatic arterial occlusion was effected in seven of the 10 patients who responded and in seven of the 12 nonresponding patients. Such manipulation of hepatic arterial blood flow did not have a significant effect on the survival duration in either group. Retreatment of patients with colon cancer and liver metastases by hepatic arterial infusion of fluorodeoxyuridine and mitomycin C can result in significant prolongation of survival in patients with response to this treatment.     

Long-term survivors of colorectal cancer with unresectable hepatic metastases

Five patients with colorectal cancer and unresectable synchronous liver metastases have survived for over five years at this writing. Four of the five had multiple metastases over both lobes, as diagnosed preoperatively, and the other had multiple metastases in the right lobe not evident preoperatively. The primary foci were excised completely in four patients. For one patient with multiple metastases limited to the right lobe, the postoperative cancer chemotherapy prescribed was intravenous mitomycin C (MMC; 12 mg) and oral ftorafur (a derivative of 5-FU) for a total dose of 291 gm over 63 weeks. The remaining four patients underwent postoperative intra-arterial infusion therapy with the average total dose of 20.5 mg of MMC plus 5600 mg of 5-FU; subsequently, they received protracted chemotherapy with oral ftorafur of 354 gm as an average, with little or no side effects. In these four patients, duration of intra-arterial treatment was an average of 3.2 weeks, and the subsequent oral treatment continued for an average of 85 weeks. Recent hepatic echography and CEA determinations show these patients to be free from intrahepatic metastasis.     

Hepatic arterial chemotherapy for colorectal cancer metastatic to the liver

Hepatic metastases of colorectal origin are resistant to radiation and immunotherapy. Traditional intravenous chemotherapy produces responses in 10% to 30% of patients, and surgical resection is feasible in approximately 20% of patients who have a solitary or unilobar lesion. Infusion of cytotoxic agents into the hepatic artery, introduced 2 decades ago, is the most promising form of therapy for unresectable hepatic metastases. Fluorouracil, floxuridine, and mitomycin have been most commonly administered by hepatic arterial infusion. The recent development of a totally implantable pump has allowed prolonged ambulatory infusion of chemotherapeutic agents into the hepatic artery. We review the recent data on the pharmacology, therapeutic outcome, administration techniques, and complications of hepatic arterial chemotherapy. Future trials in this area should use uniform stratification variables and standardized criteria for evaluating response, time to progression, and survival.     

Transbrachial hepatic arterial chemotherapy using an implanted infusion pump

Two patients with hepatic metastases from colonic cancer were treated with hepatic arterial FUDR using an innovative drug infusion system. The two patients reported underwent transbrachial hepatic artery catheterization with a 5 French polyethylene catheter. This catheter was amputated just distal to its exit from the brachial artery and attached to a totally implantable, percutaneously refillable drug infusion pump placed in the infraclavicular position. The patients received FUDR at flow rates of 3–4 ml/day. The pumps were refilled weekly by percutaneous injection. One patient was treated for seven weeks, and another for ten weeks without technical difficulties. This innovative approach offers marked improvement in comfort and convenience for patients who are candidates for long-term hepatic artery chemotherapy, and avoids the morbidity of laparotomy for direct hepatic arterial catheterization.     

Gastroduodenal Ulcerations in Patients Receiving Selective Hepatic Artery Infusion Chemotherapy

Ninety-three patients with liver metastases underwent selective hepatic arterial infusion of chemotherapeutic agents through a surgically implanted hepatic artery catheter and pump. Fourteen patients who developed upper gastrointestinal symptoms at some time during the course of treatment were found to have gastroduodenal disease endoscopically. The severity of symptoms did not necessarily correlate with severity of endoscopic findings. There was no temporal relation between 5-fluoro-2'-deoxuridine infusion and symptoms; however, with mitomycin C, symptoms worsened in five of eight patients within 2 wk of the initial injection. Patients who received mitomycin C had more severe endoscopic findings and two of the 14 patients required partial or total gastrectomy. When biodegradable starch microspheres were coadministered with mitomycin C this was not associated with a higher incidence of gastroduodenal disease. The early experience with therapy using this system has been associated with a significant incidence of upper gastrointestinal symptoms. The presence of gastrointestinal symptoms in such patients should alert one to potentially serious disease.     

Adjuvant perioperative portal vein or peripheral intravenous chemotherapy for potentially curative colorectal cancer: long-term results of a randomized controlled trial

Background and aims  The perioperative use of a single course adjuvant portal vein infusion chemotherapy in patients with potentially curable colorectal cancer has been shown to significantly improve overall survival but did not reduce the occurrence of liver metastases (SAKK 40/81) [Swiss Group for Clinical Cancer Research (SAKK) Lancet 345(8946):349–353, 1995]. The objective of the present prospective, three-arm randomized multicenter trial was to assess whether peripheral venous administration of adjuvant chemotherapy regimen based on 5-fluorouracil (5-FU) and mitomycin C decreases the occurrence of liver metastases as well as prolongs disease-free and overall survival. Materials and methods  Stages I–III colorectal cancer patients (n = 753) were randomized to receive either surgery alone (control arm), surgery plus postoperative portal venous infusion of 5-FU 500 mg/m² plus heparin given for 24 hours for seven consecutive days plus mitomycin C 10 mg/m² given on the first day (arm 2), or surgery and the same chemotherapy regimen administered by peripheral venous route (arm 3). Results  The 5-year disease-free survival for the three treatment groups were 65% (control group), 60% (portal vein infusion, hazard ratio 1.18, p = 0.23), and 64% (intravenous infusion, hazard ratio 1.04, p = 0.76); the 5-year overall survival was 72% (control group), 69% (portal vein infusion, hazard ratio 1.21, p = 0.2), and 74% (intravenous infusion, hazard ratio 1.03, p = 0.86), respectively. A significant accumulation of early deaths were observed in the portal vein infusion group (p = 0.015). Conclusions  The present prospective randomized multicenter trial provides compelling evidence that short-term perioperative chemotherapy does not improve disease-free and overall survival in patients with potentially curative colorectal cancer. In contrary, the chemotherapy regimen administered in the present investigation seems to have potentially harmful effects, a finding which should be carefully considered in the planning of future trials. Postoperative short-term administration of 5-FU plus mitomycin C either through portal infusion or a central venous catheter is not recommended for routine use in patients with potentially curable colorectal cancer. M. Lorenz deceased.