Zinc metabolism after transcatheter arterial embolization for hepatocellular carcinoma

BACKGROUND/AIMS: Zinc metabolism after transcatheter arterial embolization (TAE) was studied in 15 cases of hepatocellular carcinoma (HCC) with liver cirrhosis (LC). METHODOLOGY: Serum zinc concentrations, 24-hr urinary excretion of zinc, blood ammonia (NH3) and plasma endotoxin (Et) levels were measured before and one, three and seven days after TAE. RESULTS: Serum zinc levels one day after TAE were decreased (p<0.05) as compared to those before TAE and then returned to pretreatment values three days or more after TAE. Urinary excretion of zinc increased (p<0.01) one day after TAE, but then returned to the pretreatment value three days after TAE. Although blood NH3 and plasma Et levels increased (P<0.05) the day after TAE, these parameters recovered on the third day. CONCLUSIONS: Decrease in the serum zinc concentration after TAE is considered to be due to changes in the zinc distribution in the body associated with endotoxemia, as well as increased urinary zinc excretion.     

Acute tumor lysis syndrome after transcatheter chemoembolization of hepatocellular carcinoma

PURPOSE: Thromboprophylaxis with heparins after total joint replacement is well accepted. The aim of this prospective randomized study was to evaluate the thrombo-prophylactical efficiency of an ankle joint moving device (Artroflow) after total knee arthroplasty. METHOD: In this prospective study 160 patients were examined who had undergone total knee arthroplasty (TKA). All of the 160 patients received Enoxaparin 1 x 40 mg subcutaneously per day. In addition to this, 90 patients received Artroflow three times a day for 30 minutes. The passive movements of the ankle joint lead to an emptying of the foot and calf veins. Except for the daily routine, we performed physical examination and ultrasound in colour, compression and duplex technique one day before surgery and at the 7th and 14th day after surgery. If a thrombosis was suspected, an ascending phlebography was carried through. RESULTS: The overall thrombosis rate was 6.3% (n = 10). 11.4% (n = 70) deep vein thromboses (DVT) could be observed in the group without Artroflow. Thrombosis occurred in the group with Artroflow in 2 cases (2.2%, n = 90). A statistical difference was found between the two patient groups (p < 0.05, Chi-Square-test). One patient was excluded from the study because of pain in the ankle joint at the fourth day of treatment. CONCLUSION: In addition to heparins, this ankle joint moving device can be recommended as a physical way to prevent DVTs in the thromboprophylaxis of total knee arthroplasty.     

Hepatic arterial infusion chemotherapy (HAI) for advanced hepatocellular carcinoma inefficacious with transcatheter arterial embolization (TAE)

For 6 patients with advanced hepatocellular carcinoma (HCC) in whom TAE was inefficacious, we tried hepatic arterial infusion chemotherapy. 5-FU 500 mg/day + CDDP 10 mg/day was administered during 5 days. The AFP level was decreased for 4 patients, and 2 patients showed a partial response in CT image. These 2 patients have been alive over 22 and 18 months, respectively. These results suggest that 5-FU + CDDP HAI might be a useful treatment of HCC inefficacious with TAE.     

Alpha-1-thymosin and transcatheter arterial chemoembolization in hepatocellular carcinoma patients: a preliminary experience

BACKGROUND/AIMS: To evaluate the tolerability and therapeutic potential of the immunostimulating adjuvant alpha-1-thymosin in patients with hepatocellular carcinoma. METHODOLOGY: Twelve patients with hepatocellular carcinoma were treated with alpha-1-thymosin (900 micrograms/m2 subcutaneously twice per week for 6 months) and transcatheter arterial chemoembolization and compared to a historical control group (matched for gender, age, Okuda staging, Child's score, alpha-fetoprotein serum levels and viral infection) treated with transcatheter arterial chemoembolization alone. RESULTS: No severe side effects were recorded in the 2 treatment groups. The combination of alpha-1-thymosin plus transcatheter arterial chemoembolization resulted in a longer survival that reached statistical significance 7 months after the end of treatment (p < 0.05). Patients receiving combined treatment demonstrated a significant increase in peripheral blood mononuclear cells expressing CD3 (p < 0.05) and CD8 (p < 0.025) 3 months after beginning treatment. They also had a significant increase (p < 0.05) in CD16+ and CD56+ cells after 1 month, and a slight reduction in mononuclear cells expressing CD25, a marker for cell activation. No alterations in the response to phytohemagglutinin stimulation were seen during the alpha-1-thymosin treatment. CONCLUSIONS: The absence of toxicity and the favourable effects observed in this open study call for a double blind control study to confirm the efficacy of the combined treatment.     

A prospective randomized administration of 5''-deoxy-5-fluorouridine as adjuvant chemotherapy for hepatocellular carcinoma treated with transcatheter arterial chemoembolization

Surgical microscopy and electrophysiological techniques were used to standardize the nomenclature for the pudendal nerve and sacral plexus according to their somatic axonal composition in the male rat. We conclude that the pudendal nerve is the segment running from the L6-S1 trunk to the sacral plexus, carrying efferent fibers to the coccygeus, internal obturator, ventral and dorsal bulbospongiosus, ischiocavernosus, external anal sphincter, and external urethral sphincter muscles, and afferent fibers from the penis, prepuce, scrotum, and ventral-proximal tail. The sacral plexus is the complex formed by the bridge-like structure connecting the pudendal nerve with the lumbosacral trunk, and two nerve branches emerging from it, one innervating the proximal half of the scrotal skin, and the other innervating the muscles at the base of the penis known as the motor branch. These branches are only considered as a part of the sacral plexus because they integrate axons from both the lumbosacral trunk and pudendal nerve. The gross anatomy of the pudendal nerve and sacral plexus has a main organization that was observed in 70% of cases, whereas the remaining 30% occurred in two variants. This nomenclature is appropriate to describe the pudendal nerve and sacral plexus in studies that involve them being lesioned or electrophysiologically analysed. A main additional finding was that two large afferent branches innervate the scrotum, one the proximal half and the other the distal half. As mentioned above, the proximal branch belongs to the sacral plexus, whereas the distal branch belongs to the pudendal nerve because all its axons travel to the cord via this nerve. Since stimulation or even manipulation of the scrotal branches resulted in the secretion of semen containing spermatozoa, it is suggested that scrotal afferents are involved in some way in the ejaculatory process, a topic that deserves further research.     

Clinical evaluation of Azasetron Hydrochloride: a new selective 5-HT3 receptor antagonist--antiemetic profile and plasma concentration in transcatheter arterial chemoembolization using CDDP for unresectable hepatocellular carcinoma

We performed a clinical evaluation on the antiemetic profile and the plasma concentration of Azasetron Hydrochloride (a new selective 5-HT3 receptor antagonist), in transcatheter arterial chemoembolization using CDDP for unresectable hepatocellular carcinoma. Antiemetic effects were examined in 32 patients in the serotone group (administration of serotone 10 mg + methylprednisolone 125 mg) and in 77 patients of the control group (administration of metoclopramide 20-30 mg + methylprednisolone 500 mg). The response rate and the CR ratio in serotone group was 97% and 66%, respectively. These results were statistically higher than in the control group. Although all patients had chronic liver diseases, no side effects and complications related to administration of serotone were observed. The average area under the concentration (AUC) curve of plasma serotone in five patients with liver cirrhosis was 531 ng.h/ml, which was greater than that of a healthy volunteer. In conclusion, serotone is a new, safe and useful antiemetic drug in TACE therapy for hepatocellular carcinoma.     

A prospective randomized evaluation of a compound of tegafur and uracil as an adjuvant chemotherapy for hepatocellular carcinoma treated with transcatheter arterial chemoembolization

A prospective randomized trial was conducted to evaluate the efficacy of long-term oral administration of low-dose tegafur combined with uracil as an adjuvant chemotherapy, following transcatheter arterial embolization (TAE) in 40 patients with hepatocellular carcinoma (HCC). Forty eligible patients were randomized into two groups: 20 with TAE plus UFT (a compound of tegafur 200 mg and uracil 448 mg per day) and 20 with TAE alone. A good necrosis rate or decrease in size of more than 70% of the original tumor mass was attained in 10 by TAE plus UFT arm and in 12 by TAE arm alone. As for the "responded" patients, there was no significant difference in the time from tumor response to tumor regrowth between the two groups. The appearance rate of ascites and/or encephalopathy in patients with chemotherapy was slightly higher than that in control patients. The median survival time was 22.7 months for TAE plus UFT arm and 28.2 months for TAE arm alone. There was no significant difference in the cumulative survival curves. In conclusion, these results indicated no substantial benefit for this chemotherapy regimen, as an adjuvant therapy for patients with HCC during repeated TAE.     

Long-term survival after resection for bronchogenic carcinoma

Of 915 resections for bronchogenic carcinoma over a 25-year period (1945-1969), 249 patients survived over 5 years; 127 of the patients eligible survived over 10 years, 61 over 15 years, and 22 over 20 years. The case material was divided into three time periods: 1945-49, 1950-59 and 1960-69, as well as by extent of resection. Lobectomy became the operation of choice, pneumonectomy being reserved for the more extensive lesions. Observed survival rates at 5, 10 and 15 years for 561 patients in the lobetomy series were 35, 22 and 15%, respectively, but strikingly increased to 41, 28 and 19% in the 1960-69 period. Observed rates for 354 patients having pneumonectomies were similar for three time periods, being 16, 8 and 6% at 5, 10 and 15 years, respectively. Relative survival rates for the lobectomy series at 5, 10 and 15 years rose from 33, 28 and 26%, repectively, in the 1950-59 period to 50, 39 and 35% in the last time period, becoming a near horizontal curve segment after 5 years. Dominant factors in survival were extent of the lesion and stage of nodal involvement, histologic type and location being less significant.     

Adverse effect of perioperative blood transfusions on survival after hepatic resection for hepatocellular carcinoma

BACKGROUND/AIMS: Experimental and clinical studies have found a relationship between blood transfusion and altered immune function. We estimated the risk of transfusions for shorter survival on patients with hepatocellular carcinoma who underwent hepatic resection. METHODOLOGY: The impact of perioperative blood transfusions on 235 patients with hepatocellular carcinoma who had resections from January 1981 to December 1988 was retrospectively examined. All patients underwent hepatic resection and received no additional chemotherapy. RESULTS: Using the Cox proportional hazard model, the number of perioperative blood transfusions was found to be a significant prognostic factor for patient outcome (p = 0.03). Overall, patients who received less than 12 transfused units had a significantly better 5-year survival rate than those who received more than 13 transfused units (46.3% vs. 24.5%, p < 0.001). This result was also seen when the patients were subdivided by stage: 5-year survival in the early stage group (57.2% vs. 35.5%, p < 0.01) and in the advanced stage group (30.0% vs. 18.2%, p < 0.05). The number of perioperative blood transfusions also influenced the survival of patients who underwent a curative resection (66.2% vs. 38.5%, p < 0.01), but did not affect the survival of those who received a non-curative resection (7.9% vs. 7.4%). CONCLUSION: This study suggests that the number of perioperative blood transfusions is a significant prognostic factor in patients with hepatocellular carcinoma who undergo hepatic resection.     

Treatment of unresectable hepatocellular carcinoma with lipiodol chemoembolization: a multicenter randomized trial. Groupe CHC

We investigated the effect of successive administrations of SA4503 (1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine dihydrochloride), a novel cognitive enhancer with high affinity and selectivity for the sigma1 receptor subtype, on the cortical cholinergic dysfunction-induced impairment of the spatial learning performance in the Morris water maze (MWM) task in rats. The impairment of the spatial learning performance was produced by the ibotenic acid-induced lesion of the basal forebrain (BF) area in rats. Escape latencies to find the platform during the training trials of the MWM task were significantly prolonged in the BF-lesioned rats compared with the sham-operated rats. Daily treatment with SA4503 (0.1-0.5 mg/kg, P.O./day) for 13 days ameliorated this learning deficit. In the probe trial, BF-lesioned rats reduced the number of times each rat crossed the former platform location during the training trials (goal area) in comparison with sham-operated rats. Successive administrations of SA4503 (0.25 mg/kg, P.O./day) also significantly increased the BF lesion-induced reduction of the number of times each rat crossed the goal area. These results suggest that the successive administrations of SA4503 attenuate the impairment of the spatial learning performance in rats with cortical cholinergic dysfunction, and that SA4503 is useful as a therapeutic drug for Alzheimer's disease.     

Preoperative transcatheter arterial chemoembolization and prognosis of patients with hepatocellular carcinomas: retrospective analysis of 120 cases

To clarify whether preoperative transcatheter arterial chemoembolization (TAE) improves the prognosis of patients with hepatocellular carcinoma (HCC) after surgery, 120 patients who had undergone hepatectomy for HCC from 1988 to 1994 and satisfied the criteria of stages II and III were enrolled in this study. Forty-four patients underwent preoperative TAE (group A) and 76 patients did not (group B). No significant differences in the outcomes were observed between these two groups. To rectify the comparison, patients with tumors 2 to 8 cm were assigned to groups A1 (n = 24) and B1 (n = 57), and those with tumors > 8 cm were assigned to groups A2 (n = 20) and B2 (n = 19), respectively. Although no significant differences in survival between groups A1 and B1 were found, group A2 presented superior 1-, 2-, and 3-year tumor-free survival rates of 80%, 55%, and 32% and 1-, 3-, and 5-year cumulative survival rates of 90%, 53%, and 42%. These figures are in comparison with the tumor-free survival rates of 50%, 22%, and 11% (p = 0.06), and the cumulative survival rates of 72%, 33%, and 11% (p = 0.01) during the same periods for group B2, respectively. The Cox regression model revealed that for patients with tumors > 8 cm, the relative risk of preoperative TAE for overall survival was 0.38 (p = 0.017), indicating that preoperative TAE might benefit patients with tumors > 8 cm but not those with tumors 2 to 8 cm.     

Monitoring of lectin-reactive alpha-fetoproteins in patients with hepatocellular carcinoma treated using transcatheter arterial embolization

We investigated hemostatic abnormalities in 37 patients with deep vein thrombosis (DVT) and pulmonary embolism (PE) (PE patients) and in 40 patients with DVT without PE (DVT patients). Plasma fibrinogen, thrombin-antithrombin complex (TAT), plasmin-plasmin inhibitor complex, fibrin-D-dimer, activated protein C (APC)-protein C inhibitor (PCI) complex, von Willebrand factor (vWf), tissue plasminogen activator (t-PA), PA inhibitor-I (PAI-1), and thrombomodulin levels in both PE and DVT patients were significantly increased compared with normal volunteers. Plasma APC-PCI complex, PAI-1, and vWf levels in PE patients were significantly higher than those in DVT patients without PE. These findings indicate that PE patients are more hypercoagulable and hypofibrinolytic than DVT patients. Plasma TAT, APC-PCI complex, PAI-1, and vWf levels were the most sensitive indicators for PE. In these patients, increases in TAT and APC-PCI complex suggest DVT and increased PAI-1 and vWf suggest the risk of onset of PE.     

Effect of percutaneous ethanol injection for postoperative recurrence of hepatocellular carcinoma in combination with transcatheter arterial embolization

BACKGROUND/AIMS: This study was conducted to clarify the effect of percutaneous ethanol injection (PEI) in combination with transcatheter arterial embolization (TAE) on prolonging the survival time of patients with postoperative recurrence of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: The subjects were 97 consecutive patients (pts) treated for postoperative recurrent HCC between February 1987 and March 1993. Of these, 25 pts received both TAE and PEI and 72 pts received TAE alone. In the TAE & PEI group, treatment was selected according to the indications: 15 pts received TAE for multiple recurrences following PEI, and the other 10 pts received PEI for a new or residual lesion following TAE. Fourteen demographic, pathological, and clinical variables were evaluated to estimate the relative risk of pts treated with TAE & PEI or with TAE alone. RESULTS: The 1-, 3- and 5- year survival rates in the TAE & PEI group were 100%, 73.2% and 27.2%, respectively, and those in the TAE alone group were 88.9%, 30.2% and 5.5%, respectively. Based on multi-variate Cox regression analysis, the relative risk of cancer death in the TAE & PEI group was 0.32 (95% confidence interval, 0.15 to 0.67). CONCLUSION: The combination of TAE and PEI had a positive palliative effect and increased survival time of patients with postoperative recurrent HCC, compared to results obtained by TAE alone.     

The safety and efficacy of transcatheter arterial chemoembolization in the treatment of patients with hepatocellular carcinoma and main portal vein obstruction. A prospective controlled study

BACKGROUND: Transcatheter arterial chemoembolization (TACE) has been contra-indicated for the treatment of patients with hepatocellular carcinoma (HCC) and main portal vein (MPV) obstruction because of the potential risk of hepatic insufficiency resulting from ischemia after TACE. The current controlled study was undertaken to assess the safety, efficacy, and predictive factors of favorable response to TACE in patients with HCC and MPV obstruction with good hepatic function and adequate collateral circulation around the MPV. METHODS: Of a total of 47 patients, 31 were treated with TACE, and 16 who declined the procedures were untreated controls. Thirty-six patients (77%) had diffuse-type HCC and 11 (23%) had nodular-type HCC. During the first week after TACE immediate postprocedural complications were evaluated, and the development of hepatic insufficiency as a late complication was assessed at the end of the fourth week. The cumulative survival rate was estimated by the Kaplan-Meier method, and predictors of better prognosis were obtained by univariate and multivariate analyses. RESULTS: Although no patients showed clinical evidence of hepatic insufficiency as an immediate complication, transient fever and abdominal pain were common. Progressive hepatic insufficiency developed at the fourth week; however, there was no difference between the treated and untreated groups. The survival time of treated patients was statistically no longer than that of untreated patients. In the univariate analysis, tumor type and size, the pattern of iodized oil uptake in the tumor, and the presence of iodized oil uptake in the tumor thrombi at the MPV significantly influenced the prognosis. Tumor type, whether treated or not, was the most important prognostic factor patients with nodular-type HCC had significantly longer survival time (median, 11 months) than those with diffuse-type HCC (median, 4 months). Regarding the efficacy of TACE, there was no statistical difference in survival between treated and untreated diffuse-type HCC patients. In comparison, with nodular-type HCC it seemed that survival time was longer for TACE-treated patients (median, 30 months) than for untreated patients (median, 7 months). CONCLUSIONS: TACE may be a safe modality for the treatment of patients with HCC and MPV obstruction, provided that the patients have good hepatic function and collateral circulation around the MPV. However, TACE was not efficacious in the treatment of diffuse-type HCC. The authors recommend TACE for treating nodular-type HCC because of the potential benefit of prolonged survival.     

Stable lipiodolized emulsions for hepatoma targeting and treatment by transcatheter arterial chemoembolization

We attempted to develop lipiodolized emulsions that remain in the tumour for a long period, release drug in a sustained release pattern, and thus improve the conventional treatment of hepatocellular carcinoma (HCC) [1]. Polyoxyethylene derivatives of hydrogenated castor oil (HCO) were the most suitable emulsifiers in stabilizing emulsions containing Lipiodol as an oil phase. The length of ethylene oxide coupled to HCO rather than the hydrophilic-lipophilic balance (HLB) values was an important factor in preparing stable emulsions and in achieving sustained-release characteristics. When distilled water was replaced with Iopamiro, a heavy water soluble contrast medium with a specific gravity of 1.335, more stable lipiodolized emulsions with longer sustained release behaviour could be prepared with smaller amount of HCO. To study the in vivo stability of the w/o Lipiodol emulsion and the sustained-release characteristics of doxorubicin from the emulsion, the pharmacokinetic study was performed with normal dogs using transcatheter arterial chemoembolization technique. The area under the plasma concentration-time curve for the first eight hours (AUC0-8) and AUCtotal values of the stabilized emulsion were three to four times higher than those of the coarse emulsion prepared lacking HCO 60. From the in vitro and in vivo studies, Lipiodol based water in oil emulsion with HCO 60 containing doxorubicin showed higher stability and released doxorubicin in a sustained fashion.     

巴曲酶灌注联合肝动脉化疗栓塞治疗原发性肝癌的临床初步研究

Objective:The aim of the study was to explore the therapeutic efficacy and safety of batroxobin in patients with primary hepatic carcinoma(PHC)and the advantages of transcatheter arterial perfusion of batroxobin combined with transcatheter arterial chemoembolization(TACE).Methods:Forty patients with PHC were randomized into experimental group(transcatheter arterial perfusion of batroxobin combined with TACE treatment,20 patients)and control group(TACE alone group,20 patients).The patients were followed up and the data were recorded,compared and analyzed.Results:(1)Compared with the control group,the FIB level in the experimental group was significantly decreased at the first month after treatment(P<0.05).(2)The baseline of the tumor was shortened in both groups after the treatment.There was a significant difference between the two groups at different time intervals(P<0.05).(3)After the treatment,there was a significant difference of progression-free survival(PFS)levels between the two groups(t=2.877,P<0.05).(4)The incidence of metastasis were 5.0%(1/20)in both groups at 6 months after treatment,and that after one year was 10.0%(2/20)in the experimental group and 25.0%(5/20)in the control group.However,the difference was not significant(x2=0.693,P>0.05).Conclusion:Batroxobin can rapidly and effectively decrease the FIB level of the PHC cases.Therefore it may be used as an effective and safe adjuvant drug for the treatment of primary hepatic carcinomas.Transcatheter arterial perfusion of batroxobin combined with TACE therapy has advantages in comparison with TACE alone therapy.It could be taken as a new therapeutic regimen in the PHC treatment.     

Partial hepatic resection for hepatocellular carcinoma

This review summarizes the efficacy of the most common therapeutic option for hepatocellular carcinoma (HCC), partial hepatic resection, taking into account not only its antitumoural effect, but also its consequences on survival. Partial hepatic resection results in 5 year survival rates as high as 45% in more favourable subgroups having: small tumours, well-differentiated tumours, unifocal tumours, a lack of vascular invasions, an absence of cirrhosis, and the fibrolamellar variant. Resection has been limited primarily by low resectability rates and recurrent disease. However, surgical resection in the form of partial hepatectomy is the preferred treatment for HCC. The early detection of tumours by screening high-risk populations is crucial. During the 12 year period between 1983 and 1994, hepatic resections were carried out in 382 patients with HCC. One hundred and fifty-three (40%) had HCC smaller than 5 cm in diameter. There were 294 male and 88 female patients, with an average age of 52.3 years. Among them, 45% had liver cirrhosis and 73% were positive for hepatitis B surface antigen. Two hundred and eighteen (57%) were positive for hepatitis C virus circulating antibodies (since 1991). Operative mortality was 3.9%. The overall survival rates at 1, 3 and 5 years were 71, 52 and 46%, respectively. Sex, cirrhosis, Child's staging, surgical procedure, blood loss, pathological pattern, presence of capsule, surgical margin and DNA ploidy appeared to be factors not related to prognosis. However, alpha-fetoprotein level, size (whether less than or greater than 5 cm), and vascular invasion were factors which significantly affect survival.     

Prolonged survival in selected patients following surgical resection for pulmonary metastasis from hepatocellular carcinoma

BACKGROUND: Pulmonary metastasis is the commonest site of extrahepatic spread from hepatocellular carcinoma (HCC). The aim of the present study was to evaluate the efficacy of surgical management in patients with solitary pulmonary metastases from HCC. METHODS: This was a retrospective study of patients with HCC admitted for hepatectomy from July 1972 to June 1995. The records of patients who had a pulmonary resection for histologically proven pulmonary recurrence after curative hepatectomy were selected for analysis. RESULTS: In the study interval, 380 patients with HCC underwent hepatectomy. Some 48 patients (12.6 per cent) developed pulmonary metastases documented pathologically or radiologically. Nine (seven men and two women) were suitable for curative pulmonary resection. The median disease-free survival between hepatectomy and appearance of the lung metastasis was 21 months. The median survival after pulmonary resection was 42 months, and the 1-, 2- and 5-year survival rates were 100, 78 and 67 per cent respectively. CONCLUSION: Pulmonary resection for metastases from HCC resulted in long-term survival in these highly selected patients.     

Disease-free survival and recurrence after resection of colorectal carcinoma

Recurrence data from a series of 1,315 colorectal cancer patients managed by one surgeon with potentially curative resection are presented. Complete follow-up information was available on 1,287 (98%) patients. At the time of the last recurrences, 164 and 232 months for rectal and colonic tumours respectively, the long-time recurrence rate was significantly (P = 0.001) higher for rectal tumours (42%) than for colonic (33%). Although local recurrences tended to be more common in rectal than in colonic tumours (18% compared to 15%), only those in contiguity with the operative area were significantly (P less than 0.005) more common in rectal tumours. Systemic recurrences were also significantly (P less than 0.025) commoner for rectal tumours. The greater recurrence rates in rectal tumours were associated with significantly (P less than 0.001) higher incidence of stage C tumours shorter recurrence-free survival in rectal stage C tumours (P = 0.001) and higher incidence of pulmonary metastases (P less than 0.001).