Long-term results of the European achalasia trial: a multicentre randomised controlled trial comparing pneumatic dilation versus laparoscopic Heller myotomy.

OBJECTIVE: Achalasia is a chronic motility disorder of the oesophagus for which laparoscopic Heller myotomy (LHM) and endoscopic pneumodilation (PD) are the most commonly used treatments. However, prospective data comparing their long-term efficacy is lacking. DESIGN: 201 newly diagnosed patients with achalasia were randomly assigned to PD (n=96) or LHM (n=105). Before randomisation, symptoms were assessed using the Eckardt score, functional test were performed and quality of life was assessed. The primary outcome was therapeutic success (presence of Eckardt score ≤3) at the yearly follow-up assessment. The secondary outcomes included the need for re-treatment, lower oesophageal sphincter pressure, oesophageal emptying and the rate of complications. RESULTS: In the full analysis set, there was no significant difference in success rate between the two treatments with 84% and 82% success after 5 years for LHM and PD, respectively (p=0.92, log-rank test). Similar results were obtained in the per-protocol analysis (5-year success rates: 82% for LHM vs. 91% for PD, p=0.08, log-rank test). After 5 years, no differences in secondary outcome parameter were observed. Redilation was performed in 24 (25%) of PD patients. Five oesophageal perforations occurred during PD (5%) while 12 mucosal tears (11%) occurred during LHM. CONCLUSIONS: After at least 5 years of follow-up, PD and LHM have a comparable success rate with no differences in oesophageal function and emptying. However, 25% of PD patients require redilation during follow-up. Based on these data, we conclude that either treatment can be proposed as initial treatment for achalasia. TRIAL REGISTRATION NUMBERS: Netherlands trial register (NTR37) and Current Controlled Trials registry (ISRCTN56304564).

Prospective assessment of the role of antibiotic prophylaxis in ERCP.

BACKGROUND/AIMS: Despite the existence of published recommendations, various studies of antibiotic prophylaxis have reached conflicting conclusions, and controversy exists regarding the role of antibiotic prophylaxis in ERCP. The aim of this study was to analyze the efficacy of the intramuscular administration of clindamicine and gentamicine before ERCP. METHODOLOGY: Sixty-one consecutive patients referred for ERCP were prospectively randomized to receive either clindamicine 600mg and gentamicine 80mg, both intramuscularly one hour before the ERCP (group I; 31 patients) or not (group II; 30 patients). Two blood samples were obtained from every patient (just before endoscopy and within 5 minutes of withdrawal of the endoscope) and were incubated for 7 days and examined daily for growth of bacteria. Patients were closely monitored for 7 days after endoscopy to detect the development of infectious complications. RESULTS: Only 7 cultures from 7 patients were positive. Four were obtained post-ERCP (two patients in group I and two in group II) and the remaining three before endoscopy. The post-ERCP isolated bacteria were: Streptococcus mitis, Peptoestreptococcus anaerobious, Moraxella spp and Escherichia coli. Two patients, one from each group, developed post-ERCP cholangitis that were solved with medical treatment. CONCLUSIONS: Our findings indicate that ERCP induce bacteremia in a small group of patients and suggest that prophylactic administration of clindamicine plus gentamicine does not reduce the incidence of bacteremia and cholangitis, and do not support the routine use of prophylactic antibiotics prior to ERCP.

[Evaluation of the efficacy and efficiency of a multidisciplinary unit for the treatment of patients with colorectal cancer]. / Evaluación de la eficacia y eficiencia de una unidad multidisciplinaria para la atención de pacientes con cáncer colorrectal.

INTRODUCTION: Because of the increased complexity of the diagnostic-therapeutic approach to colorectal cancer (CRC), these patients should be managed in specialized multidisciplinary units. The aim of this study was to evaluate the efficacy and efficiency of a CRC unit (CRCU) in the diagnostic-therapeutic management of these patients. PATIENTS AND METHODS: Two groups of 50 patients with colon cancer treated in our center before and after the implementation of the CRCU were selected. Fulfillment with the protocol in terms of tumoral staging, surgical and adjuvant treatment, follow-up, interval until treatment, hospital stay, morbidity and early mortality, and the overall duration of the diagnostic-therapeutic process was analyzed. In addition, clinical workload was evaluated and a cost-minimization analysis was performed. RESULTS: The CRCU reduced the interval until surgery (20.3 12.0 vs 28.0 20.4 days; p = 0.05), hospital stay (9.8 7.7 vs 14.5 9.3 days: p = 0.01), the time to the start of adjuvant treatment (29.4 10.2 vs 39.7 19.8 days; p = 0.03) and the overall duration of the process (60.4 23,8 vs 82.1 46.1 days; p = 0.05), representing a saving of 978.85 E per patient. This improvement took place despite an increase in clinical workload (24% in 5 years in relation to the number of admissions) and had no effect on morbidity (26 vs 24%; NS) or immediate mortality (6 vs 4%; NS). CONCLUSION: Specialized multidisciplinary units increase the efficacy and efficiency of the management of patients with CRC.

Sphincterotomy in the treatment of biliary leakage.

BACKGROUND/AIMS: Endoscopic procedures such as sphincterotomy and endobiliary stenting have proved useful to solve postoperative bile leakage. We have assessed the outcome of a series of such patients initially treated with endoscopic sphincterotomy, having reserved stent placement for treatment failures only. METHODOLOGY: Twenty-five consecutive patients referred for endoscopic assessment of postoperative bile leaks and fistulas after cholecystectomy (n = 15), orthotopic liver transplantation (n = 9) and hepatic resection due to cystic hydatid disease (n = 1) underwent endoscopic retrograde cholangiopancreatography and sphincterotomy using a standard papillotome. Sphincterotomy was followed by stone extraction using a Dormia basket if common bile duct lithiasis were present. RESULTS: Bile leaks healed early after endoscopic sphincterotomy in 22 out of 25 patients (88%). Common bile duct stones were also retrieved in 6 of these patients. Bile duct stenosis due to surrounding pancreatic inflammation was demonstrated in two of the patients in which sphincterotomy failed to stop bile leakage. CONCLUSIONS: Endoscopic sphincterotomy alone should at present be considered a highly effective treatment to resolve postsurgical bile leaks unless bile strictures are present.

Influence of Helicobacter pylori infection and eradication on blood lipids and fibrinogen.

BACKGROUND: An association between Helicobacter pylori infection and heart disease has been suggested. A potential mechanism may be inflammation-induced atherogenic changes of lipoproteins, but epidemiological studies have provided conflicting results. METHODS: In a prospective multicentre study, 830 patients submitted for endoscopy and H. pylori testing were evaluated. Of the 686 H. pylori-positive patients, 487 received and 199 did not receive eradication treatment. Serum lipids and plasma fibrinogen were measured at baseline in all patients and 3 months later in those initially positive for H. pylori. RESULTS: H. pylori had no influence on baseline lipid or fibrinogen levels. Increases in high-density lipoprotein cholesterol were observed in 368 patients who received eradication treatment and in 193 untreated patients: 0.06 mmol/L (P=0.000) and 0.07 mmol/L (P=0.009), respectively. Similar minor increases in total cholesterol and triglycerides occurred in both groups. Lipid changes were related to symptom relief and a reduction in smoking. Eradication therapy was associated with a minor decrease in plasma fibrinogen irrespective of the resolution of infection. CONCLUSIONS: H. pylori has no influence on blood lipids or fibrinogen. Both the eradication of infection and symptomatic treatment without eradication are associated with minor lipid changes related to symptom relief and lifestyle modifications. Thus, the inflammatory changes associated with H. pylori are unlikely to affect lipoprotein or fibrinogen metabolism.

Endoscopic injection therapy in bleeding Mallory-Weiss syndrome: a randomized controlled trial.

BACKGROUND: Endoscopic injection is widely used in the therapy of bleeding gastroduodenal ulcers, but its role in the management of bleeding Mallory-Weiss tears has not been properly assessed. METHODS: Sixty-three patients undergoing emergency endoscopy in whom there was a high index of suspicion that a Mallory-Weiss tear was the source of bleeding were randomly assigned to undergo endoscopic injection therapy (epinephrine and polidocanol) or no endoscopic therapy in 2 university-affiliated hospitals. Rates of recurrent bleeding, transfusion requirements, complications, mortality, and length of hospital stay were determined for both groups of patients. RESULTS: Bleeding recurred in 8 patients in the control group versus only 2 in the endoscopic treatment group (25.8% vs. 6.2%, p < 0.05). Hospital stay was longer for the control group (5.5 +/- 0.2, median 6.0, range 2.0-8.0 days vs. 3.4 +/- 0.2, median 3.0, range 2.0-6.0 days; p < 0.001). There was a trend toward a higher transfusion requirement after endoscopy in the control group versus the patients treated by injection (0.9 +/- 0.2, median 0.0, range 0.0-4.0 units vs. 0.2 +/- 0.1, median 0.0, range 0.0-2.0 units; p = 0.09). No complications or adverse events caused by endoscopic injection were noted. Two patients in the control group died of causes unrelated to bleeding. CONCLUSIONS: Endoscopic injection therapy is a useful option in the management of patients with Mallory-Weiss syndrome at high risk for recurrent bleeding.

The effects of vasoactive drugs on hepatic blood flow changes induced by CO2 laparoscopy: an animal study.

UNLABELLED: Laparoscopic surgery is associated with systemic and splanchnic hemodynamic alterations. Recent data suggest that small-dose dobutamine may attenuate the reduction in splanchnic blood flow associated with increments in intraabdominal pressure. We conducted this study to analyze the effects of dopamine and dobutamine on the hepatic circulation in this setting. Twenty-one pigs were anesthetized and mechanically ventilated. A flow-directed pulmonary artery and carotid artery catheters were inserted. Perivascular flow probes were placed around the main hepatic artery and the portal vein. CO2 was insufflated into the peritoneal cavity to reach an intraabdominal pressure of 15 mm Hg. After 60 min, animals received dopamine (5 microg x kg(-1) x min(-1); n = 8), dobutamine (5 microg x kg(-1) x min(-1); n = 8), or saline (n = 5) for 30 min. Pneumoperitoneum induced significant increases in heart rate, mean arterial pressure, and systemic vascular resistance, with decreases in cardiac output and hepatic artery and portal vein blood flows. Dobutamine infusion, in contrast to dopamine, corrected, at least in part, cardiac output, systemic vascular resistance, and hepatic artery blood flow alterations, but neither drug restored total hepatic blood flow. IMPLICATIONS: Hepatic blood flow decreases during laparoscopic surgery. A small-dose infusion of neither dobutamine nor dopamine corrects the total hepatic blood flow impairment, but the former is able to restore the hepatic arterial blood supply in an animal model mimicking this condition.

Un paciente con rectorragias

La emisión de sangre roja a través del ano constituye una situación clínica extraordinariamente prevalente que a menudo se debe a la existencia de afección anorrectal benigna, aunque en un porcentaje no despreciable de casos supone una manifestación clínica de enfermedades mucho más relevantes. El espectro de entidades clínicas que pueden ocasionar rectorragia se extiende desde las hemorroides hasta el cáncer colorrectal, pasando por las malformaciones vasculares, la enfermedad inflamatoria intestinal y la enfermedad diverticular, entre otras.En la mayoría de ocasiones, los datos obtenidos en la anamnesis y la exploración física no permiten obtener un diagnóstico de certeza, lo que obliga a efectuar exploraciones complementarias (AU)

Laparoscopic-assisted vs. open colectomy for colorectal cancer: influence on neoplastic cell mobilization.

Laparoscopic surgery for treatment of colorectal cancer has been suggested to enhance tumor dissemination. Recently, molecular techniques have been developed to detect micrometastatic disease in patients with solid tumors, with a higher accuracy than cytologic or immunohistochemical approaches. This study was undertaken to investigate the potential harmful effects of laparoscopic-assisted colectomy on neoplastic cell mobilization in patients with resectable colorectal cancer. Fifty patients with nonmetastatic colorectal cancer were randomly assigned to laparoscopic-assisted (LAC, n = 26) or open (OC, n = 24) colectomy. Peripheral venous blood samples were obtained preoperatively, immediately after tumor removal, and 24 hours later. In 10 patients from each treatment group, portal blood and peritoneal fluid samples were also obtained before and after resection. Neoplastic cells were detected by means of reverse transcriptase-polymerase chain reaction targeted to carcinoembryonic antigen (CEA) transcription. CEA mRNA was detected in peripheral venous blood samples from 35 of 50 colorectal cancer patients preoperatively. Among those 15 baseline-negative patients, four experienced conversion 24 hours after tumor resection (2 [33%] of 6 in the LAC group vs. 2 [22%] of 9 in the OC group; NS). At that time point, clearance of CEA mRNA expression was observed in 14 of the 35 baseline-positive patients (9 [45%] of 20 in the LAC group vs. 5 [33%] of 15 in the OC group; NS). In addition, only one patient in the LAC group with baseline-negative CEA mRNA expression experienced portal blood conversion after tumor removal, although his peripheral blood level remained negative. Finally, baseline peritoneal fluid CEA mRNA expression was never detected, but one patient in each group became positive postoperatively. These results confirm that preoperative and perioperative mobilization of neoplastic cells is a frequent occurrence in patients with colorectal cancer, but the surgical approach (LAC vs. OC) does not seem to be a determining factor.

Lack of prognostic influence of circulating tumor cells in peripheral blood of patients with colorectal cancer.

BACKGROUND AND AIMS: Circulating tumor cells in peripheral blood may be detected using high-sensitivity molecular techniques in several types of solid neoplasms, but their significance in colorectal cancer is controversial. The aim of this study was to assess the prognostic value of carcinoembryonic antigen (CEA) messenger RNA (mRNA) detection in peripheral blood samples from patients with colorectal cancer. METHODS: Peripheral vein blood samples from 95 consecutive patients with histologically confirmed colorectal carcinoma were obtained immediately before surgery to determine the presence of circulating tumor cells by use of a reverse-transcription polymerase chain reaction targeting CEA mRNA. Endpoints of the study were disease-free and overall survival. Results are referred to the whole series and, more importantly, to the 68 patients who underwent surgery for cure. RESULTS: After a median follow-up of 42 months, 19 of 68 patients (28%) operated on for cure had tumor relapse. In addition, 50 of 68 patients (73%) were alive. The probability of disease-free and overall survival was dependent on lymph node metastases and degree of differentiation, but not on the presence of circulating tumor cells (disease-free survival: relative risk, 1.00; 95% confidence interval [CI], 0.39-2.22, P = 0.99; overall survival: relative risk, 0.91, 95% CI, 0.34-2.43; P = 0.84). Similar results were obtained when all 95 patients with colorectal cancer were analyzed (disease-free survival: relative risk, 1.11; 95% CI, 0.63-1.95; P = 0.71; overall survival: relative risk, 1.21; 95% CI, 0.63-2.30, P = 0.55). CONCLUSIONS: Preoperative detection of blood circulating tumor cells by means of reverse-transcription polymerase chain reaction of CEA does not have prognostic significance in patients with colorectal cancer.

La detección precoz del cáncer colorrectal

El avance en el conocimiento de los mecanismos fisiopatológicos implicados y de la historia natural del cáncer colorrectal ha propiciado la implementación de programas de cribado y vigilancia. Estos programas, dirigidos al diagnóstico precoz de esta neoplasia, incluyen diversos procedimientos, entre los que destacan las pruebas de detección de sangre oculta en heces, las exploraciones endoscópicas o radiológicas y, más recientemente, determinados análisis genéticos (AU)

Dobutamine restores intestinal mucosal blood flow in a porcine model of intra-abdominal hyperpressure.

OBJECTIVE: To assess the effects of dopamine and dobutamine administration on the systemic and mesenteric (macro- and microvascular) circulatory disturbances induced by intra-abdominal hyperpressure. DESIGN: Prospective, randomized study. SETTING: Animal research laboratory in a university hospital. SUBJECTS: Twenty-five pigs of either gender, weighing 30-35 kg. INTERVENTIONS: Animals were anesthetized, and their lungs were mechanically ventilated. Pulmonary artery flotation and carotid artery catheters were inserted for hemodynamic monitoring and blood sampling. A perivascular flow probe was placed around the superior mesenteric artery, and a laser Doppler probe was positioned in the lumen of the ileum to measure arterial and intestinal mucosal blood flows, respectively. CO2 was insufflated into the peritoneal cavity to reach an intra-abdominal pressure of 15 mm Hg, and 60 mins later, animals received dopamine (5 microg/kg/min; n = 10), dobutamine (5 microg/kg/min; n = 10), or saline (n = 5) for 30 mins. MEASUREMENTS AND MAIN RESULTS: Peritoneal CO2 insufflation induced significant increases in heart rate, arterial pressure, and systemic vascular resistance with concomitant decreases in cardiac output and superior mesenteric arterial and intestinal mucosal blood flows. Although dobutamine infusion reversed the decrease in cardiac output, it failed to restore superior mesenteric artery blood flow; however, intestinal mucosal blood flow returned to baseline levels. Dopamine also attenuated the decrease in cardiac output, but it had no beneficial effect on splanchnic hemodynamic variables. CONCLUSIONS: Low-dose infusion of dobutamine, but not dopamine, corrects the intestinal mucosal perfusion impairment induced by moderate increases in intra-abdominal pressure.

Differential effects of a nitric oxide donor on reperfusion-induced microvascular dysfunction in diabetic and non-diabetic rats.

AIMS/HYPOTHESIS: Diabetes is associated with a high incidence of ischaemic disease and impaired nitric oxide responses. Therefore, the aim of the present study was to assess the effect of nitric oxide on ischaemia/reperfusion (I/R)-induced microvascular responses in an experimental model of diabetes. METHODS: Leucocyte-endothelial cell interactions were studied in mesenteric venules after superior mesenteric artery occlusion (10 min), at 10 and 30 min of reperfusion in control and streptozotocin-induced diabetic rats. An oxidant-sensitive fluorochrome was used to measure oxidant production during reperfusion. P-selectin and ICAM-1 expression were quantified at 10 and 30 min of reperfusion respectively, using radiolabelled monoclonal antibodies. The transcription of ICAM-1 mRNA was determined by northern blot. The effect of spermine NONOate, given locally, on all variables studied, was assessed in additional experiments. RESULTS: Ischaemia/reperfusion induced an enhanced leucocyte accumulation and oxidant production in diabetic animals. Moreover, I/R enhanced endothelial P-selectin expression in both groups of animals, whereas it only up regulated ICAM-1 endothelial expression and mRNA expression in diabetic rats. Spermine NONOate abrogated to a similar extent leucocyte adhesion and emigration in control and diabetic animals, although the mechanisms underlying this protective effect appear to be different. In control rats Spermine NONOate effectively prevented P-selectin up regulation, whereas in diabetic rats NO appreciably attenuated the rapid up regulation of ICAM-1 by preventing its transcription. CONCLUSIONS/INTERPRETATION: Expression of ICAM-1 is rapidly increased in diabetic, but not control, animals exposed to I/R. The increased endothelial cell adhesion molecule expression, leucocyte-endothelial cell adhesion and oxidant stress induced by I/R in diabetic rats are significantly attenuated by exogenous NO. [Diabetologia (1999) 42: 1350-1358]

[The evaluation of a new immunoenzyme analysis for the detection of Helicobacter pylori infection in stool samples]. / Evaluación de un nuevo enzimoinmunoanálisis para la detección de la infección por Helicobacter pylori en muestras fecales.

BACKGROUND: Detection of bacterial antigen in stool specimens (HpSAT) is a new promising tool for diagnosing Helicobacter pylori infection. OBJECTIVE: To evaluate diagnostic accuracy of HpSAT in the diagnosis of Helicobacter pylori infection. PATIENTS AND METHODS: We evaluate the presence of Helicobacter pylori infection by the rapid urease test and the 13C-urea breath test in endoscopic biopsies. Patients who were positive for both tests were considered to have Helicobacter pylori infection. Patients negative for both tests were considered free of infection. The presence of Helicobacter pylori infection was also determined in stool specimens by means of HpSAT. RESULTS: The sensitivity of HpSAT was 92.8%, the specificity 92.3%, the positive predictive value 98.1% and the negative predictive value 75%. CONCLUSIONS: HpSAT is a reliable tool for diagnosing Helicobacter pylori infection.

Reperfusion-induced oxidative stress in diabetes: cellular and enzymatic sources.

Reactive oxygen metabolites (ROMs) have been implicated in the pathogenesis of the inflammatory response to ischemia/reperfusion (I/R), which is exacerbated in diabetes. This study revealed an increased (P < 0.01) ROMs production in mesenteric tissue (measured using the oxidant-sensitive fluorochrome dihydrorhodamine 123) after I/R in control and diabetic rats, with larger increments (P <0.0001) observed in the latter group, that was associated with an increased inflammatory response measured by intravital microscopy. Either xanthine oxidase inhibition, superoxide scavenging, ICAM-1 immunoneutralization, or blockade of platelet-activating factor or leukotrienes effectively reduced leukocyte recruitment and ROMs production in control and diabetic rats. Moreover, neutrophils from diabetic rats showed an enhanced production of ROMs in vitro in basal and stimulated conditions. We conclude that the oxidative stress during reperfusion is markedly enhanced in diabetes and this appears to result from increased leukocyte recruitment and a higher capacity of diabetic leukocytes to generate ROMs in response to stimulation.

[Typification of strains of Helicobacter pylori by the detection of the cagA gene and subtypes of the vacA gene]. / Tipificación de cepas de Helicobacter pylori mediante la detección del gen cagA y subtipos del vacA.

BACKGROUND: Helicobacter pylori infection is probably the most common chronic bacterial infection in the world. The consequences of infection are pathologies like peptic ulcer, chronic gastritis, gastric cancer and gastric MALT lymphoma. The aim of this study was to detect the vacuolating cytotoxin gene (vacA) type, the cytotoxin-associated gen (cagA) of H. pylori isolates and study their association with the vacuolising activity. MATERIAL AND METHODS: Gastric biopsy specimens were obtained from dyspeptic patients. Isolates were further genotypically typed by PCR. RESULTS: All strains studied were vacA+ and 55% were cagA+. All cytotoxic strains were cagA+, subtype vacA s1/m1 and corresponded to patients with peptic ulceration. The cagA- strains (11) corresponded to subtype s2/m2. We didn't demonstrate vacuolising activity on subtypes s1/m2 and s2/m2. CONCLUSIONS: A high genetic diversity exists among strains in our environment. The subset of bacteria, vacA s1/m1/cagA+, is associated with vacuolising activity in culture cells (tox+).

Helicobacter pylori, hyperammonemia and subclinical portosystemic encephalopathy: effects of eradication.

BACKGROUND/AIMS: An involvement of Helicobacter pylori in the development of hepatic encephalopathy in cirrhotic patients has been proposed, but data confirming such an association are lacking. This prospective study aimed to assess whether ammonia levels and indicators of subclinical portosystemic encephalopathy were influenced by H. pylori status in a series of 62 cirrhotic patients. The effects of H. pylori eradication on such parameters were also investigated. METHODS: Fasting blood ammonia levels, mental state, number connection test, flapping tremor, and EEG tracings were recorded at baseline, and in H. pylori-positive patients (as diagnosed by rapid urease test and 14C-urea breath test) these parameters were reassessed 2 months following eradication therapy. RESULTS: In this series of non-advanced cirrhotic patients, the prevalence of H. pylori infection was 52%. No significant differences were observed between H. pylori+ and H. pylori- cases with respect to fasting venous blood ammonia concentration (47+/-24 vs. 43+/-22 micromol/l) or to the remaining parameters assessing portosystemic encephalopathy. In addition, H. pylori eradication failed to induce any significant variation in either fasting blood ammonia levels (from 45+/-23 to 48+/-26 micromol/l) or neurologic disturbances. CONCLUSION: These results indicate that H. pylori infection is not a major contributing factor to either fasting blood ammonia levels or parameters assessing subclinical portosystemic encephalopathy in patients with non-advanced liver cirrhosis.

VCAM-1 and ICAM-1 mediate leukocyte-endothelial cell adhesion in rat experimental colitis.

BACKGROUND & AIMS: The molecular mechanisms responsible for leukocyte recruitment in experimental colitis are poorly understood. The aims of this study were to measure expression of endothelial intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) and to determine their role in leukocyte recruitment in experimental colitis. METHODS: Rats with trinitrobenzene sulfonic acid (TNBS)-induced colitis and control rats were studied 1, 7, or 21 days after treatment. ICAM-1 and VCAM-1 expressions were measured by the double radiolabeled antibody technique. Leukocyte-endothelial cell interactions were determined in colonic venules by fluorescence intravital microscopy. Therapeutic effects of treatment with anti-VCAM-1 antibodies were also assessed. RESULTS: Colonic endothelial ICAM-1 was constitutively expressed and did not increase in colitic animals. In contrast, constitutive expression of VCAM-1 was low but markedly increased (6-fold) 1 and 7 days after induction of colitis. Increased colonic expression of VCAM-1 paralleled macroscopic damage score, myeloperoxidase activity, and increased leukocyte adhesion in colonic venules. The latter was significantly decreased by immunoneutralization of ICAM-1 and completely abrogated by immunoneutralization of VCAM-1. Long-term administration of anti-VCAM-1 antibody resulted in significant attenuation of colitis. CONCLUSIONS: Induction of colitis in rats by TNBS is followed by up-regulation of endothelial VCAM-1. VCAM-1 and constitutive ICAM-1 are major determinants of leukocyte recruitment to the inflamed intestine.