[Role of echoendoscopy in diagnostic and therapeutic strategies in gastrointestinal oncology].
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Publications and source records attributed to J I Elizalde.
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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.
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.
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.
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.
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.
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.
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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.
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]
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.
BACKGROUND: Patients who have prosthetic heart valves, previous history of endocarditis, and surgically constructed systemic-pulmonary shunts or conduits should receive prophylactic antibiotics before colonoscopy. The usefulness of this approach in cirrhotic patients remains unknown. The present study prospectively assesses the incidence of bacteremia in these patients. METHODS: Lower intestinal endoscopy was performed in 58 cirrhotic 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 72 hours after endoscopy to detect the development of infectious complications. RESULTS: Only 6 cultures from 6 patients were positive. Four were obtained post-endoscopy and the remaining 2 before colonoscopy but the corresponding post-endoscopy samples were negative. All organisms recovered were normal skin flora. All patients, including those with positive cultures, remained asymptomatic during the 72 hours after the procedure. CONCLUSIONS: Our findings indicate that lower intestinal endoscopy does not induce bacteremia in cirrhotic patients with or without ascites in the absence of gastrointestinal bleeding and do not support the routine use of prophylactic antibiotics in these patients.
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.
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+).
BACKGROUND/AIMS: In experimental portal hypertension, blood hemoglobin levels have been shown to influence the hyperdynamic circulatory state. The aim of this study was to assess the hemodynamic effects of increasing hemoglobin concentration in human portal hypertension. METHODS: Sixteen cirrhotic patients recovering from a variceal bleeding episode were randomly assigned to receive two units of packed red cells or 500 ml of a protein solution. Systemic and portal hemodynamics, and rheological and hormonal parameters were measured at baseline and after expansion. RESULTS: Both groups were similar with respect to the degree of liver failure, severity of the bleeding episode, activation of the endogenous vasopressor systems, and hemodynamic parameters. The administration of either erythrocytes or a protein solution prompted a similar increase in total blood volume and suppression of vasopressor systems. Both groups of patients experienced similar increases in wedged hepatic venous pressure. Hepatic venous pressure gradient was not significantly modified but tended to increase in erythrocyte-transfused patients. Cardiopulmonary pressures increased, but this increment was significant in the non-blood-transfused patients only. Cardiac output decreased in erythrocyte-transfused patients, while it increased in the group receiving a protein solution. Red blood cell transfusion resulted in an increase in systemic vascular hindrance (resistance/blood viscosity), whereas the administration of a protein solution prompted a decrease in this parameter, thus reflecting true vasoconstriction and vasodilation, respectively. CONCLUSIONS: An increase in blood hemoglobin in acutely anemic cirrhotic patients attenuates their hyperdynamic circulation beyond viscosity-dependent changes, an effect which might be counteracted by the effects on portal venous pressure gradient.
Nuclear factor kappB (NFkappaB) is a transcription factor that controls several genes important for immunity and inflammation. The aim of this study was to assess if activation of NFkappaB plays a role in the pathogenesis of inflammatory bowel disease (IBD), and whether steroid treatment affects NFkappaB activation. Activation of NFkappaB was analysed in colon biopsy samples of 13 patients with active IBD (8 Crohn's colitis, 5 ulcerative colitis) by electrophoretic mobility-shift assays, under basal conditions and 3 weeks after treatment with 0.75 mg kg(-1) day(-1) prednisolone. The presence of interleukin-8 mRNA in biopsies was assessed by RT-PCR. A specific NFkappaB band was present in all nuclear extracts from inflamed mucosa, whereas the band was barely detectable in uninflamed colonic mucosa. NFkappaB bands were super-shifted by antibodies against p50 subunit, whereas antibodies against p65, p52, c-Rel, or Rel B did not modify the mobility of the band. Increased interleukin-8 mRNA was detected at the same sites of NFkappaB activation. Steroid-induced healing of colonic inflammation was associated with disappearance of NFkappaB from nuclear extracts. These results support the notion that NFkappaB plays an important role in the pathogenesis of IBD, and that blockade of NFkappaB activation is one of the mechanisms by which steroids suppress the inflammatory cascade in IBD.
BACKGROUND AND STUDY AIMS: Hemorrhage is one of the most common severe complications after endoscopic sphincterotomy (ES) and the mortality after surgical treatment can be as high as 50%. We prospectively evaluated the effect of injection treatment in nine patients with appreciable hemorrhage after ES. PATIENTS AND METHODS: Bleeding was detected immediately after ES in five patients and 48, 72, 120 and 216 hours after the procedure in the remaining four. Patients were treated with a combined injection of epinephrine and polidocanol (1-3 and 3-6 ml, respectively) into the bleeding site. RESULTS: Treatment was effective in arresting hemorrhage in all cases. Two patients had abnormal clotting tests, which emphasizes the importance of identifying risk factors for hemorrhage before ES. No patient required operation and there were no late complications related to the injection during a mean follow-up period of six months. CONCLUSIONS: Our results suggest that bleeding after sphincterotomy can be safely and effectively controlled by a combined epinephrine and polidocanol injection, thereby avoiding operation.
OBJECTIVE: To investigate whether gastric intramucosal acidosis is associated with a decreased gastric mucosal blood flow in mechanically ventilated patients. DESIGN: Prospective, clinical investigation. SETTING: University hospital intensive care unit. PATIENTS: Seventeen mechanically ventilated patients with stable hemodynamic status. INTERVENTIONS: Gastric tonometry and endoscopic assessment of mucosal blood flow. MEASUREMENTS AND MAIN RESULTS: Six patients had gastric intramucosal acidosis (intramucosal pH [pHi] of 7.24 +/- 0.06), whereas the remaining 11 patients had pHi values within the normal range (7.44 +/- 0.01). No differences were found between intramucosal acidotic and nonacidotic patients with respect to their general and hemodynamic characteristics. Patients with intramucosal acidosis had a lower gastric mucosal blood flow, as assessed by laser-Doppler flowmetry, than nonacidotic patients (1.4 +/- 0.1 vs. 2.1 +/- 0.2 volts, respectively; p < .05). Reflectance spectrophotometry disclosed that patients with low gastric pHi had also a significantly (p < .05) lower hemoglobin content index (61 +/- 4 arbitrary units) than patients with normal pHi (81 +/- 3 arbitrary units), whereas oxygen saturation index was similar for both groups. CONCLUSION: Our results support the hypothesis that gastric mucosal hypoperfusion underlies the development of intramucosal acidosis in mechanically ventilated patients.