Exploring the combined action of lifetime alcohol intake and chronic hepatotropic virus infections on the risk of symptomatic liver cirrhosis. Collaborative Groups for the Study of Liver Diseases in Italy.

Although alcohol intake and hepatitis B and C virus (HBV and HCV) infections are the major determinants of liver cirrhosis (LC) in western countries, the joint effect of these factors on LC risk has not yet been adequately studied. Data from three case-control studies performed in Italy were used. Cases were 462 cirrhotic patients admitted to Hospitals for liver decompensation. Controls were 651 inpatients admitted for acute diseases unrelated to alcohol. Alcohol consumption was expressed as lifetime daily alcohol intake (LDAI). Three approaches were used to explore the interaction structure. The Breslow and Storer parametric family of relative risk functions showed that an intermediate structure of interaction from additive to multiplicative was the most adequate one. The Rothman synergism index showed that the interaction structure between LDAI and viral status differed significantly from the additive model in particular for high levels of alcohol intake. When multiple regression additive and multiplicative models were compared after adjustment for the known confounding variables. a trend of the interaction structure towards the multiplicative model was observed at increasing levels of consumption. Better methods are needed for assessing mixed interaction structures in conditions characterized by multifactorial etiologies like cirrhosis of the liver.

Meta-analysis of alcohol intake in relation to risk of liver cirrhosis.

The heterogeneity in the results of observational studies that investigated the association between alcohol consumption and risk of liver cirrhosis was analysed by means of a meta-analysis that included 15 articles published from 1978 to 1997. Relative risks associated with low levels of alcohol intake (25 g/day) ranged from 1.5 [95% confidence interval (CI): 1.4-1.5] for a linear model fitting the results of the six studies performed in Mediterranean areas, to 3.6 (95% CI 3.1-4.3) for a quadratic model fitting the results of the nine studies performed in other areas. A strong indication of heterogeneity was observed when combining all studies. Quadratic term of alcohol intake, quality of the study and area in which the study was performed explained most of this heterogeneity. Efforts should be made to explain the strong heterogeneity in the trend estimates. Reproducible methods to collect relevant and valid information on alcohol intake should be developed and the role of drinking patterns and viral and nutritional factors in modifying the effect of alcohol on the risk of liver cirrhosis should be investigated.

Attributable risk for symptomatic liver cirrhosis in Italy. Collaborative Groups for the Study of Liver Diseases in Italy.

BACKGROUNDS/AIMS: Knowledge of the proportion of liver cirrhosis attributable to the main risk factors is largely based on methodologically questionable clinical reports. METHODS: The proportion of newly diagnosed cases of symptomatic liver cirrhosis attributable to known risk factors was estimated by a case-control study performed during 1989-1996 in 23 medical divisions of several hospitals distributed throughout Italy. Cases were 462 inpatients with cirrhosis admitted for the first time for liver decompensation. Controls were 651 patients admitted during the same period and to the same hospitals as the cases, for acute diseases unrelated to alcohol and virus infection. The proportion of symptomatic liver cirrhosis cases due to alcohol intake and hepatitis B and C viruses and the combination of these was expressed as the population attributable risk. RESULTS: Attributable risks were 67.9% (95% confidence interval (CI): 53.8-79.4) for alcohol, 40.1% (95% CI: 35.3-45.2) for hepatitis C virus and 4.4% (95% CI: 2.5-7.6) for hepatitis B virus. The three factors together explained 98.1% (95% CI: 81.6-99.6) of cases in men and 67.0% (95% CI: 50.4-85.8) in women. CONCLUSIONS: Alcohol is the risk factor with the highest impact on symptomatic liver cirrhosis risk in Italy. From a public health viewpoint, with the elimination of the well-known risk factors (particularly alcohol and hepatitis C virus), liver cirrhosis should become a rare disease.

Alcohol consumption and micronutrient intake as risk factors for liver cirrhosis: a case-control study. The Provincial Group for the study of Chronic Liver Disease.

PURPOSE: The purpose of this study was to assess the relationship of alcohol consumption and intake of 15 selected micronutrients with risk of liver cirrhosis. METHODS: Data from a case-control study performed in 1989-1990 in central Italy involving 115 incident cases and 167 hospital controls were used. RESULTS: Cases and controls did not differ for mean daily intake of calories, carbohydrates, lipids, and proteins. Significant direct dose-response relationships between the intakes of vitamin A and iron and the risk cirrhosis were observed, while significant protective effects were obtained for the intakes of vitamins B2 (riboflavin) and B12. Different patterns of the joint effect of nutrients and alcohol were also observed. The intakes of vitamin A and iron were significantly associated with the risk of cirrhosis in lifetime teetotalers (odds ratios (OR) and 95% coincidence intervals (CI) of 33.6 (1.2-979.9) and 37.9 (1.8-819.4) for higher intake of vitamin A and iron, respectively) and in consumers of < 50 g/day of alcohol (vitamin A: OR 45.0; 95% CI, (2.6-774.6); iron: OR, 73.6; 95% CI, 4.3-999). The OR associated with intakes of vitamins B2 (riboflavin) and B12 were not significant for the first two categories of alcohol use, while a higher intake of these two vitamins reduced the risk of cirrhosis associated with alcohol consumption above 50 g/day; the ORs (95% CI) were 23.0 (2.7-198.9) and 104.4 (7.2-999), respectively, for higher and lower intakes of riboflavin and 12.8 (1.8-88.1) and 138.4 (14.0-999), respectively, for higher and lower intake of vitamin B12. CONCLUSION: These findings might explain at least a portion of the individual susceptibility to alcohol-induced liver damage.

Minimal residual disease in metastatic breast cancer: treatment with IFN-beta, retinoids, and tamoxifen.

The aim of this pilot study was to investigate if chemotherapy (CT) followed by the combination of interferon-beta (IFN-beta), retinoids, and tamoxifen could be effective in the treatment of metastatic breast cancer (MBC). Thirty-six patients with stage IV carcinoma of the breast were treated with six courses of cyclophosphamide, 5-fluorouracil, 4-epidoxorubicin, vincristine, and prednisone every 3 weeks (FECPV), followed by two courses of non-cross-resistant drugs, methotrexate, mitomycin C, and mitoxantrone (MMM). Treatment was continued, in responders, with low dose IFN-beta, retinyl palmitate, and tamoxifen until relapse of the disease occurred. Among 36 evaluable patients, 23 achieved a clinical response (64 %) (95 % confidence interval [c.i.] 46 %-79 %), 7 had stable disease (19%), and 6 (17%) progressed. Leukopenia occurred in 15 patients, thrombocytopenia in 6, and anemia in 11. Sixteen patients had nausea/vomiting, stomatitis was observed in 9, and diarrhea occurred in 3. Toxicity from maintenance therapy was mild and mainly hepatic. Median response duration was 31 months (range 5-107). Median overall survival was 32 months (9-108). Our study shows that this combined approach for the treatment of MBC is feasible, with an acceptable toxicity.

Incidence of malignant lymphoproliferative diseases by stage and histological variants in central Italy: a population based study 1982-1994.

A population-based epidemiological study that concerns the estimate of incidence rates of Hodgkin's Disease (HD) and Non Hodgkin's Lymphoma (NHL) in a Central Italy area was performed. All the new cases of HD and NHL diagnosed from 1982 till 1994 in the target population were collected by multiple information sources. The temporal trend of incidence rates and their relation with age, gender and histological variant were analyzed. In the considered period 95 cases of HD and 297 cases of NHL were collected. Constant age-adjusted incidence rates of HD were observed, while an increasing trend of NHL incidence rates was observed especially for cases at presentation in stage III and IV and for histotypes G, H and I. The investigations carried out on patients with HD have shown that this condition prevails in women in the younger age groups, while in men presentation occurs more frequently at an advanced age. Moreover the authors have confirmed previous reports of a distinctly increased incidence of nodular sclerosis in contrast to the other three histological variants which do not show a juvenile peak but a gradual increase in incidence with advancing age. The epidemiological features of NHL's observed correspond to the standard incidence rates obtained in Europe and throughout the world. NHL's appear to be a pathological entity typical of elderly patients: however high-grade NHL's, in contrast to low-grade NHL's, was present with increased frequency also in childhood and in patients under the age of 30.

Female sex and the risk of liver cirrhosis. Collaborative Groups for the Study of Liver Diseases in Italy.

BACKGROUND: Evidence on gender-related differences in susceptibility to alcohol-induced liver diseases is questionable with regard to both methodologic and clinical aspects. With the aim to assess the role of gender in the risk of liver cirrhosis, independently and in combination with known risk factors, data from three case-control studies performed in various Italian areas were analysed. METHODS: The cases were 462 cirrhotic patients (300 men and 162 women) admitted for the first time to hospital for liver decompensation. Controls were 651 patients (355 men and 296 women) admitted to the same hospitals during the same period as the cases, for acute diseases unrelated to alcohol. Alcohol consumption was expressed as lifetime daily alcohol intake. RESULTS: A significant and independent associations between alcohol intake, chronic hepatitis B and C virus infections, and the risk of liver cirrhosis was observed. The effect of alcohol intake was multiplicatively increased in women. The odds ratio (OR) increased from 1.0 (reference category: men, lifetime abstainers) to 31.4 (95% confidence interval (CI), 10.3-95.8) in men drinking more than 100 g/day of alcohol, and from 2.2 (95% CI, 1.0-7.1) in abstaining women to 44.8 (95% CI, 8.2-224.0) in women drinking more than 100 g/day of alcohol. An increased risk of liver cirrhosis associated with female gender independently of alcohol consumption and virus infection was also observed. CONCLUSIONS: A higher susceptibility to alcohol-induced liver diseases was confirmed for women, and an independent effect of female sex on the risk of cirrhosis was observed. Besides alcohol and viruses, some unknown gender-related factor might then be involved in the occurrence of the disease.

Is alcohol a risk factor for liver cirrhosis in HBsAg and anti-HCV negative subjects? Collaborative Groups for the Study of Liver Diseases in Italy.

BACKGROUND/AIMS: In order to evaluate the association between alcohol intake and the risk of liver cirrhosis in the absence of B and C hepatitis viruses, we analyzed data from three hospital-based case-control studies performed in various Italian areas. METHODS: From the case and control series we excluded HBsAg and/or anti-HCV positive patients. Cases were 221 cirrhotic patients admitted for the first time to hospital for liver decompensation. Controls were 614 patients admitted to the same hospitals during the same period as the cases for acute diseases unrelated to alcohol. Alcohol consumption was expressed as lifetime daily alcohol intake (LDAI). RESULTS: We found a dose-effect relationship between LDAI and the risk of liver cirrhosis (LC). Considering the extreme LDAI categories (LDAI = 0 g: lifetime teetotallers and LDAI > or = 100 g), the LC odds ratio (OR) increased from 1.0 (reference category) to 44.7 (95% confidence interval: 95% CI: 20.0-99.9). An increased risk of LC associated with the female gender independent of alcohol consumption was also observed (OR = 2.9; 95% CI: 1.8-4.6). CONCLUSIONS: Alcohol intake acts as a risk factor for symptomatic liver cirrhosis also in the absence of HBV and/or HCV infection. Besides alcohol and viruses, some unknown gender-related factors might be involved in the occurrence of the disease.

Are the recent trends in liver cirrhosis mortality affected by the changes in alcohol consumption? Analysis of latency period in European countries.

OBJECTIVE: A striking reduction of alcohol-related problems, such as liver cirrhosis death rates, has been observed in many western countries in recent years. It might be expected that these declines are accompanied by a lagged reduction in per capita alcohol consumption, since many years of intake are required for cirrhosis of the liver to develop (lag theory). The main aim of this study is to verify the validity of the lag theory, taking as target populations those resident in European countries. METHOD: Changes in liver cirrhosis death rates in 22 European countries between 1970 and 1089 were regressed onto changes in per capita alcohol consumption (1961-89) to evaluate the latency period between trends of these variables. RESULTS: Eastern countries had a latency period between trends in alcohol consumption and in mortality rates of many years, whereas in northern, western and southern Europe cirrhosis mortality rates were explained by their relationship with per capita alcohol consumption, which lagged a few years. In some countries, an immediate contemporary appearance of the two phenomena was observed. CONCLUSIONS: These results suggest that the lag theory cannot fully explain the relationship between changing alcohol consumption and cirrhosis mortality and that other factors, such as alcoholism treatment rates, are involved in the wide geographical variability of the latency periods.

Activity of standard-dose carboplatin, cyclophosphamide, and etoposide in patients with metastatic breast cancer with previous exposure to anthracyclines.

The prognosis for patients with metastatic breast cancer, progressing after anthracycline-based cytotoxic therapy, is poor, and new treatment strategies are needed. Carboplatin (CBDCA), etoposide (VP-16), and cyclophosphamide (CTX) combination therapy has proved activity against a wide variety of tumors. This study was undertaken to evaluate the activity and toxicity of standard doses of CBDCA, VP-16, and CTX administered as salvage chemotherapy in a group of patients with metastatic breast cancer previously treated with two chemotherapy regimens, including anthracyclines. Thirty patients received an average 3.5 courses of the following treatment: CBDCA, 300 mg/m2, and CTX, 500 mg/m2, on day 1; VP-16, 60 mg/m2, on days 2, 3, and 4. Thirteen patients (43%) achieved an objective response, seven (23%) stabilized, while 10 (34%) progressed. The median response duration was 11.5 months (range, 1-19); the median overall survival from protocol entry was 9.1 months (range, 1.5-26). Gastrointestinal toxicity was noted in six patients, and hematologic toxicity of grade 3-4 was found in 11 patients. The combination of CTX, CBDCA, and VP-16 at this dose and schedule is active as salvage treatment of patients with breast cancer. Even when the toxicity was severe, responders had good symptom palliation with a substantial improvement in performance status.

Randomized trial of filgrastim vs. sequential filgrastim and molgramostim after dose-intensified carboplatin, cyclophosphamide, and etoposide: a phase I pilot study.

This phase I randomized study was designed in order to verify if the sequential administration of filgrastim, a granulocyte colony-stimulating factor (G-CSF), and molgramostim, a granulocyte-macrophage colony-stimulating factor (GM-CSF), was superior to filgrastim alone in improving tolerance of dose-intensified carboplatin (CBDCA), cyclophosphamide (CTX), and etoposide (VP-16). A group of 10 heavily pretreated patients with stage IV disease and no therapeutic option were enrolled into the study. They received two courses of the same chemotherapy with CTX and VP-16 at doses of 1,500 mg/m2 and 400 mg/m2, respectively. CBDCA doses were escalated from 450 to 600 mg/m2. After chemotherapy each patient was allocated randomly to receive either 14 days of G-CSF (arm A) or 7 days of G-CSF followed by 7 days of GM-CSF (arm B). Crossover in the second chemotherapy course was accomplished. Both G-CSF and GM-CSF were given 5 microg/kg/day, subcutaneously. Twenty chemotherapy courses are evaluable, 10 in each arm. Absolute neutrophil count < 1 x 10(3)/microl was observed for 54 days in arm A vs. 68 days in arm B (P < 0.02); platelet (PLT) count < 20 x 10(3)/microl, 57 days vs. 30 days (P < 0.01); days of hospitalization 35 vs. 16 (P < 0.38); PLT transfusion, 107 vs. 58 (P < 0.01); packed red blood cell unit transfusions, 15 vs. 5 (P < 0.13). Seven patients had responses. These data indicate that dose-intensified chemotherapy may be delivered without bone marrow or peripheral stem cell support, with acceptable toxicity, and that, while G-CSF alone shortens days of neutropenia, the combination of the two cytokines shortens the time of thrombocytopenia and decreases the number of PLT transfusions.

Prognostic factors for long-term survival in cirrhotic patients after the first episode of liver decompensation.

BACKGROUND/AIMS: Prognostic studies on cirrhosis are needed, since several attempts to obtain better survival predictors than the empirically derived Child-Pugh's score have failed. METHODS: Four hundred and ninety-four consecutive in-patients with cirrhosis at the first episode of decompensation (ascites, jaundice, encephalopathy) and/or of digestive haemorrhage from ruptured oesophageal varices were followed from admission (1983-1989) to 1993, studying the relationship between 26 prognostic variables and survival. Three prognostic models were constructed using Cox's regression model and the Receiver Operating Characteristic (ROC) analysis was used to compare their predictive ability. RESULTS: During follow-up 351 patients died (median cumulative survival 1.82 years). Child-Pugh's score (explicative variable of the first Cox's model), albumin and encephalopathy among the 5 Child-Pugh variables (second model), and oesophageal varices haemorrhage and 3 biochemical indexes among the 7 significant variables on univariate analysis (third model) correlated with survival. The area under the ROC curve of the first model did not significantly differ from that for the other 2 models. CONCLUSIONS: The Child-Pugh's score is still the best and simplest index for assessing the prognosis of liver cirrhosis.

Trends of liver cirrhosis mortality in Europe, 1970-1989: age-period-cohort analysis and changing alcohol consumption.

BACKGROUND: Since the mid 1970s, a striking reduction in alcohol-related problems has been observed in many Western countries. Liver cirrhosis mortality is considered to be a major indicator of alcohol-related problems in the general population. The aim of the present study is to describe liver cirrhosis mortality trends in European countries between 1970 and 1989. METHODS: This is a descriptive study on liver cirrhosis mortality in 25 European countries, and in four grouped European regions. A Poisson log-linear age-period-cohort model is used to clarify whether the recent trend in mortality represents a short-term fluctuation or an emerging long-term trend. In addition, a descriptive comparison between trends in per capital alcohol consumption and liver cirrhosis mortality is conducted. RESULTS: In the whole European population and in that of Western and Southern Europe increasing period effects were observed until the second half of the 1970s followed by a decline in the next periods. In Eastern Europe the decline in period effects started in the first half of the 1980s, whereas in Northern Europe an increasing period effect was observed until the second half of the 1970s, followed by a stabilization. Similar trends were observed for per capita alcohol consumption. The age effect analysis showed a continuously rising effect in Eastern Europe, whereas an attenuation of the effect at around age 65 years was observed in Western Europe. Intermediate patterns were observed in Southern and Northern Europe. The birth cohort effect suggested that in the Western and Southern populations mortality could continue to decrease over the next decade, while in Eastern and Northern mortality is still rising and this will probably continue for the next decade. CONCLUSIONS: The age-period-cohort analysis allows targeting of health care and prevention programmes based on future trends. Aetiological and prognostic factors act differently in Europe. A better understanding of the trends would require more detailed information on alcoholism treatment rates, alcohol habits, viral hepatitic infections and other factors involved in the aetiopathogenesis of the disease.

Mortality in psychiatric hospital patients: a cohort analysis of prognostic factors.

BACKGROUND: This work followed a group of patients living in a psychiatric hospital in Central Italy in 1978 at the time of enforcement of the Italian reform law (No. 180) for closing down mental hospitals. The study had the following aims: a) to compare in terms of mortality patients discharged into the community with patients who did not experience deinstitutionalization; b) to determine the survival of the cohort of patients and to analyse prognostic risk factors for death; c) to analyse differences in mortality rates between psychiatric patients and the general population. METHODS: The study was designed as an historical follow-up investigation. Univariate (product limit) and multivariate (proportional hazards model) methods were used to estimate prognostic variables and related death risks. Mortality was assessed using standardized mortality ratios (SMR) on the entire cohort as well as after stratification according to age, sex, cause of death and discharge status, assuming the Abruzzo Region's population as standard. RESULTS: Length of hospitalization and discharge from hospital are prognostic variables for death risk, with relative risks respectively of 4.22 (95% confidence interval [CI]: 2.41-7.40) for a length of hospitalization of 10-25 years, and 8.13 (95% CI: 4.73-13.88) for non-discharge. The global SMR of the cohort was 2.68 (95% CI: 2.42-3.07). Non-discharged patients showed higher SMR than discharged. Excess mortality was found both in males and females for circulatory, respiratory and undefined diseases. A significantly lower mortality for cancer was observed in male patients. A strong excess mortality was observed in younger patients (20-29 years: SMRmales = 43.57; SMRfemales = 97.52). CONCLUSIONS: Longer periods of hospitalization and non-discharge from hospital are the main risk factors for death in psychiatric patients, who globally experience higher death rates than the general population for a wide spectrum of causes of death, whatever their diagnosis or gender. These findings strongly suggest positive actions in order to overcome the effects of institutionalization.

Flow cytometric DNA analysis of cirrhotic liver cells in patients with hepatocellular carcinoma can provide a new prognostic factor.

BACKGROUND: DNA flow cytometry of hepatocellular carcinoma (HCC) cells has been investigated in many studies, but, to the best of our knowledge, there are no data on DNA analysis of cirrhotic parenchyma around the HCC. In this study, cell kinetics and ploidy of parenchymal cells around HCC were performed to ascertain if this would predict the possibility of recurrence in the cirrhotic areas. METHODS: The DNA content of 93 cases of HCC and of cirrhotic liver around the tumor nodules was analyzed by flow cytometry. Ploidy and proliferative index of HCC and cirrhotic liver were compared with macroscopic, histologic, and clinical features of each case and linked with the behavior of these tumors. Survival curves were assessed according to the Kaplan-Meier method. A multivariate analysis based on Cox proportional hazards regression model was performed on cases of diploid cirrhosis cells in which the S-phase fraction was evaluable. RESULTS: The univariate analysis of survival suggested significant roles for age, number of intrahepatic nodules, Edmondson-Steiner's classification, portal invasion, vascular invasion, presence of necrosis, hepatitis B surface antigen, alpha-feto-protein, Child's score, ploidy, and S-phase fraction of HCC cells. The DNA analysis of the cirrhotic cells showed that polyploidy was dramatically reduced in patients with HCC, compared with normal hepatocytes, and aneuploid clones were present among diploid cells. High S-phase fraction of cirrhotic cells and Child-Pugh classification were the strongest independent parameters affecting the tumor behavior in this study. CONCLUSIONS: The results of this study suggest that S-phase fraction of cirrhotic liver parenchyma may be employed as a new parameter in the prognostic evaluation of HCC patients.

Randomized trial of 5-fluorouracil and high-dose folinic acid with or without alpha-2B interferon in advanced colorectal cancer.

We evaluated the role of low-dose alpha-2b interferon, added to chemotherapy, for advanced colorectal cancer; we randomized patients, to either a combination chemotherapy of 5-fluorouracil (5-FU) and high-dose folinic acid (HDFA) or the same regimen plus interferon. Between January 1990 and March 1992, 100 untreated patients (PTS) with advanced colorectal cancer, 53 men and 47 women, with an ECOG performance status (PS) of < or = 3, were randomized to either HDFA 200 mg/m2 iv bolus and 5FU 370 mg/m2 in 15-min iv infusion days 1-5 every 4 weeks (arm A), or the same chemotherapy plus IFN 3 x 10(6) IU subcutaneously three times a week in chemotherapy intervals (arm B). A total of 97 PTS are evaluable for response, toxicity, and survival; 3 PTS are not evaluable in arm B for major protocol violations. PTS characteristics were well balanced in both arms for age (median, 64 years), disease-free survival, and disease site. ECOG PS was 0 in 28% of PTS in arm A and in 13% in arm B. Response rates were as follows: arm A, 40%; and arm B, 23%. Median time to failure was as follows: 10.2 months arm A versus 9 months arm B. Median survival was as follows: 13.3 months arm A versus 10.9 months arm B. Grade 3 haematological toxicity was 9% of PTS in both arms. Gastrointestinal toxicity was as follows: 17% arm A versus 22% arm B. The cost of drugs expressed per m2/month was $60 in arm A and $390 in arm B. The results show that IFN at the schedule and doses employed adds no benefit to the combination of 5FU/HDFA.

Prognostic factors for postoperative recurrence of Crohn's disease. Gruppo Italiano per lo Studio del Colon e del Retto (GISC)

UNLABELLED: Prognostic factors for postoperative recurrence of Crohn's disease (CD) have been widely investigated but not yet clearly identified. PURPOSE: Aim of this study was, therefore, to analyze the association between demographic, clinical, laboratory, and surgical characteristics of patients and the cumulative probability of endoscopic postoperative recurrence. METHODS: The study was performed in 110 patients who were enrolled in the Italian multicenter, randomized, controlled trial on the effectiveness of 5-aminosalicylic acid (5-ASA) in the prevention of postoperative recurrence in CD. Patients had undergone their first intestinal resection for CD of the terminal ileum with or without involvement of cecum ascending colon. Recurrence was defined on the basis of endoscopy. The following variables were evaluated as potential prognostic factors: gender, age, years since diagnosis, clinical course (perforative and non-perforative), Crohn's Disease Activity Index score, white blood count, erythrocyte sedimentation rate, C-reactive protein, and orosomucoids assessed before the operation. Timing of operation (elective or urgent), type of anastomosis (end-to-end, end-to-side, side-to-side), and prophylactic treatment were also evaluated. Colon ileoscopy was performed at 6, 12, 24, and 36 months after operation. The association between variables and the cumulative proportion of recurrence was analyzed both by univariate analysis (life table method, log-rank test) and multivariate regression analysis (Cox's model, stepwise procedure). RESULTS: Results of this study indicate that, of the features considered before surgery, only leukocytosis (white blood count, >9,000 ml) was significantly associated with an increased risk of recurrence (P < 0.05) at univariate analysis. This finding was not confirmed by multivariate analysis. A trend toward a higher risk of recurrence for patients who have had a resection with end-to-end anastomosis compared with those who have had a resection and other types of anastomosis was also observed. This trend reached significantly in the group of patients submitted to treatment with 5-ASA. The multivariate analysis showed that 5-ASA-treated patients with end-to-end had a risk of recurrence more than threefold higher than those with other types of anastomosis (relative risk, 3.40; 95 percent confidence interval, 1.00-11.96; P < 0.03). CONCLUSIONS: From a practical point of view, it has been estimated that the combination of intestinal resection plus side-to-side or end-to-side anastomosis with oral 5-ASA treatment reduces by 64 percent the postoperative recurrence rate in CD at three years follow-up.