Long-term follow-up of 1,000 patients cured of Helicobacter pylori infection following an episode of peptic ulcer bleeding.

OBJECTIVES: To evaluate the effect of Helicobacter pylori (H. pylori) eradication on ulcer bleeding recurrence in a prospective, long-term study including 1,000 patients. METHODS: Patients with peptic ulcer bleeding were prospectively included. Prior non-steroidal anti-inflammatory drug (NSAID) use was not considered exclusion criteria. H. pylori infection was confirmed by rapid urease test, histology, or (13)C-urea breath test. Several eradication therapies were used. Subsequently, ranitidine 150 mg o.d. was administered until eradication was confirmed by (13)C-urea breath test 8 weeks after completing therapy. Patients with therapy failure received a second, third, or fourth course of eradication therapy. Patients with eradication success did not receive maintenance anti-ulcer therapy and were controlled yearly with a repeat breath test. NSAID use was not permitted during follow-up. RESULTS: Thousand patients were followed up for at least 12 months, with a total of 3,253 patient-years of follow-up. Mean age 56 years, 75% males, 41% previous NSAID users. In all, 69% had duodenal ulcer, 27% gastric ulcer, and 4% pyloric ulcer. Recurrence of bleeding was demonstrated in three patients at 1 year (which occurred after NSAID use in two cases, and after H. pylori reinfection in another one), and in two more patients at 2 years (one after NSAID use and another after H. pylori reinfection). The cumulative incidence of rebleeding was 0.5% (95% confidence interval, 0.16-1.16%), and the incidence rate of rebleeding was 0.15% (0.05-0.36%) per patient-year of follow up. CONCLUSION: Peptic ulcer rebleeding virtually does not occur in patients with complicated ulcers after H. pylori eradication. Maintenance anti-ulcer (antisecretory) therapy is not necessary if eradication is achieved. However, NSAID intake or H. pylori reinfection may exceptionally cause rebleeding in H. pylori-eradicated patients.

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.

Wireless capsule endoscopy in patients with obscure gastrointestinal bleeding: a comparative study with push enteroscopy.

BACKGROUND: The identification and treatment of lesions located in the small intestine in obscure gastrointestinal bleeding is always a clinical challenge. AIM: To examine prospectively the diagnostic precision and the clinical efficacy of capsule endoscopy compared with push enteroscopy in obscure gastrointestinal bleeding. METHODS: Forty-two patients (22 men and 20 women) with obscure gastrointestinal bleeding (overt bleeding in 26 cases and occult blood loss with chronic anaemia in 16) and normal oesophagogastroduodenoscopy and colonoscopy were analysed. All patients were instructed to receive the capsule endoscopy and push enteroscopy was performed within the next 7 days. Both techniques were blindly performed by separate examiners. The diagnostic yield for each technique was defined as the frequency of detection of clinically relevant intestinal lesions carrying potential for bleeding. RESULTS: A bleeding site potentially related to gastrointestinal bleeding or evidence of active bleeding was identified in a greater proportion of patients using capsule endoscopy (74%; 31 of 42) than enteroscopy (19%; eight of 42) (P = 0.05). The most frequent capsule endoscopy findings were: angiodysplasia (45%), fresh blood (23%), jejunal ulcers (10%), ileal inflammatory mucosa (6%) and ileal tumour (6%). No additional intestinal diagnoses were made by enteroscopy. In seven patients (22%), the results obtained with capsule endoscopy led to a successful change in the therapeutic approach. CONCLUSIONS: Compared with push enteroscopy, capsule endoscopy increases the diagnosis yield in patients with obscure gastrointestinal bleeding, and allows modification on therapy strategy in a remarkable proportion of patients.

[The applicability and diagnostic effectiveness of transjugular liver biopsy]. / Aplicabilidad y rentabilidad diagnóstica de la biopsia hepática transyugular.

BACKGROUND: The aim of this study was to evaluate the applicability, the diagnostic profitability and the incidence of complications associated with tranjugular liver biopsy associated with the measurement of the hepatic venous pressure gradient (HVPG). PATIENTS AND METHODS: The clinical histories of 829 consecutive patients in whom transjugular liver biopsy was performed from 1982 to 1993 were reviewed. The diagnostic value of the sample obtained was evaluated in all the patients and the HVPG determined. Moreover, the size of the greatest fragment obtained during biopsy was also determined. RESULTS: Material for histologic study was obtained in 95% of the cases. In 70% the biopsy was diagnostic, in 11% it provided data contributing to diagnosis and in 19% it was not useful. Potentially severe complications were presented in 0.8% of cases being fatal in one (0.1%). The obtention of a fragment of small size was significantly associated with the presence of disease with marked fibrosis and high HVPG. A HVPG > 10 mmHg in patients with a suspicion of liver disease had a sensibility of 92% and a specificity of 63% for the diagnosis of hepatic cirrhosis. In 83% of patients with a GPVH > 10 mmHg in whom the biopsy was not useful, the diagnosis of hepatic cirrhosis was performed by other methods. CONCLUSIONS: Transjugular biopsy in a safe, effective diagnostic method in patients with severe coagulation disorders. The appearance of the material obtained and the HVPG provide useful information for diagnosis although the biopsy is not diagnostic.

[Duodenal obstruction by biliary lithiasis (Bouveret's syndrome)]. / Obstrucción duodenal por litiasis biliar (síndrome de Bouveret).

The case of an 81-year-old woman admitted for abdominal pain, nausea and vomiting diagnosed with Bouveret syndrome is presented. This rare disease, consisting in obstruction of gastric emptying by gallstones located in the pylorus or the duodenal bulb predominates in elderly women and represents 2% of the cases of biliary ileum. Diagnosis is based on the clinical manifestations, the existence of aerobilia, visualization of lithiasis by radiography, echography or fiber gastroscopy and the demonstration of duodenal obstruction. The treatment of choice is surgery consisting in gastrotomy or enterotomy and extraction of the stone. The importance of diagnosis and early treatment is emphasized to improve prognosis.

[The clinicopathological characteristics and prognosis of tumors of the gastrointestinal stroma]. / Características clinicopatológicas y pronóstico de los tumores de la estroma gastrointestinal.

Gastrointestinal stromal tumors form a small percentage of digestive tract tumors. They have recently been the subject of a new histopathologic classification made possible by immunohistochemical techniques. A series of criteria has been proposed which enables the identification of the most malignant and clinically aggressive tumors. We present five patients who were diagnosed with gastrointestinal stromal tumor, each of which had distinct characteristics. The different diagnostic tests performed, the difficulties of reaching a diagnosis as well as the treatment and distinct behavior of these tumors are discussed.

[Simultaneous presentation of autoimmune thyroiditis and celiac disease in an adult]. / Tiroiditis autoinmune y enfermedad celíaca del adulto de presentación simultánea.

Celiac disease may be associated with other underlying autoimmune diseases. Among these, thyroid disease has been described in around 10% of the cases with hypothyroidism being the most frequently reported. Clinical suspicion of thyroid involvement in patients with celiac disease is difficult since the symptomatology is scarce or is masked by the picture of malabsorption. Nonetheless, its detection is important since it is not solved by gluten free diet and its correction requires specific treatment. Thyroid function studies, in addition to determination of antithyroglobulin and antimicrosomal antibodies, should be considered in celiac patients refractory to conventional dietetic treatment. We herein present the case of a 65-year-old woman who consulted for a malabsorption syndrome in whom celiac disease of the adult was simultaneously presented with hyperthyroidism secondary to autoimmune thyroiditis.

[Role of capsule endoscopy in patients with obscure digestive bleeding]. / Papel de la cápsula endoscópica en los pacientes con hemorragia digestiva de origen indeterminado.

INTRODUCTION: The identification and localization of lesions located in the small intestine that may provoke gastrointestinal bleeding is difficult. OBJECTIVE: To analyze the role of capsule endoscopy in patients with obscure digestive bleeding and to compare the results obtained with those of enteroscopy. PATIENTS AND METHODS: Twenty-one patients with obscure digestive bleeding (acute hemorrhage in 11 patients and chronic anemia in 10) and normal total fibergastroscopy and fibrocolonoscopy were analyzed. All patients were instructed to receive the capsule and enteroscopy was performed after 1 week. The results obtained using both procedures were independently compared and without knowledge of the results of the other procedure. RESULTS: Visualization of findings potentially related to gastrointestinal bleeding was significantly greater (p < 0.05) using the capsule (14 of 21 patients [66%]) than with enteroscopy (4 of 21 patients [19%]). The most frequent lesions were angiodysplasias and jejunal ulcers. In 4 patients, the results obtained led to a change in therapeutic approach. One patient with jejunal stenosis and two with ileal lesions underwent surgery, which confirmed the diagnosis of Crohn's disease in the first patient and carcinoid tumor in the remaining two. Another patient with evidence of angiodysplasia and bleeding was effectively treated with Argon-beam during enteroscopy. The capsule was well tolerated in all patients. In the patient with jejunal stenosis, capsule extraction was required during surgery. CONCLUSIONS: Capsule endoscopy allows adequate visualization of the entire small intestine and its diagnostic efficacy is greater than that of enteroscopy in patients with obscure digestive bleeding. Moreover, in our series, this procedure allowed modification of therapy in one out of every five patients.

[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.

[Effects of percutaneous intrahepatic portosystemic shunt on splanchnic and systemic hemodynamics in patients with portal hypertension]. / Efectos de la derivación portosistémica percutánea intrahepática sobre la hemodinámica esplácnica y sistémica en pacientes con hipertensión portal.

Transjugular intrahepatic portosystemic shunt (TIPS) is a calibrated shunt directed at reducing the portal pressure gradient with a low incidence of hepatic encephalopathy and deterioration of hepatocellular function. The present study investigated the effects of TIPS on splanchnic and systemic hemodynamics on liver function and on the development of encephalopathy. A group of 30 patients treated with TIPS were included in the study: 26 patients with hepatic cirrhosis for an hemorrhagic episode by esophageal varices not controlled by medical treatment and sclerotherapy and in 4 cases with the Budd-Chiari syndrome for ascites refractory to medical treatment. Before, at 24 hours and 2 months after TIPS, the portal pressure gradient, cardiopulmonary pressure and cardiac output, blood flow of the azygos vein, and hepatic clearance of indocyanine green as indexes of liver function were determined. TIPS significantly decreased the portal pressures gradient and azygos blood flow. This was associated with a significant increase in cardiac output and a significant decrease in peripheral vascular resistance and hepatic clearance of indocyanine green. Portal flow deviated by TIPS was greater in the 9 patients (30%) who developed hepatic encephalopathy during follow up. In conclusion, TIPS effectively reduces portal hypertension. Nonetheless, it is associated with an increase in hyperdynamic circulation, a high incidence of encephalopathy and a deterioration in liver function.

Meta-analysis: predictors of rebleeding after endoscopic treatment for bleeding peptic ulcer.

BACKGROUND: Determining the risk of rebleeding after endoscopic therapy for peptic ulcer bleeding (PUB) may be useful for establishing additional haemostatic measures in very high-risk patients. AIM: To identify predictors of rebleeding after endoscopic therapy. METHODS: Bibliographic database searches were performed to identify studies assessing rebleeding after endoscopic therapy for PUB. All searches and data abstraction were performed in duplicate. A parameter was considered to be an independent predictor of rebleeding when it was detected as prognostic by multivariate analyses in ≥2 studies. Pooled odds ratios (pOR) were calculated for prognostic variables. RESULTS: Fourteen studies met the prespecified inclusion criteria. Pre-endoscopic predictors of rebleeding were: (i) Haemodynamic instability: significant in 9 of 13 studies evaluating the variable (pOR: 3.30, 95% CI: 2.57-4.24); (ii) Haemoglobin value: significant in 2 of 10 (pOR: 1.73, 95% CI: 1.14-2.62) and (iii) Transfusion: significant in two of six (pOR not calculable). Endoscopic predictors of rebleeding were: (i) Active bleeding: significant in 6 of 12 studies (pOR: 1.70, 95% CI: 1.31-2.22); (ii) Large ulcer size: significant in 8 of 12 studies (pOR: 2.81, 95% CI: 1.98-4.00); (iii) Posterior duodenal ulcer location: significant in four of eight studies (pOR: 3.83, 95% CI: 1.38-10.66) and (iv) High lesser gastric curvature ulcer location: significant in three of eight studies (pOR: 2.86; 95% CI: 1.69-4.86). CONCLUSIONS: Major predictors for rebleeding in patients receiving endoscopic therapy are haemodynamic instability, active bleeding at endoscopy, large ulcer size, ulcer location, haemoglobin value and the need for transfusion. These risk factors may be useful for guiding clinical management in patients with PUB.

Risk of upper gastrointestinal ulcer bleeding associated with selective cyclo-oxygenase-2 inhibitors, traditional non-aspirin non-steroidal anti-inflammatory drugs, aspirin and combinations.

BACKGROUND: The risks and benefits of coxibs, non-steroidal anti-inflammatory drugs (NSAIDs), and aspirin treatment are under intense debate. OBJECTIVE: To determine the risk of peptic ulcer upper gastrointestinal bleeding (UGIB) associated with the use of coxibs, traditional NSAIDs, aspirin or combinations of these drugs in clinical practice. METHODS: A hospital-based, case-control study in the general community of patients from the National Health System in Spain. The study included 2777 consecutive patients with endoscopy-proved major UGIB because of the peptic lesions and 5532 controls matched by age, hospital and month of admission. Adjusted relative risk (adj RR) of UGIB determined by conditional logistic regression analysis is provided. RESULTS: Use of non-aspirin-NSAIDs increased the risk of UGIB (adj RR 5.3; 95% confidence interval (CI) 4.5 to 6.2). Among non-aspirin-NSAIDs, aceclofenac (adj RR 3.1; 95% CI 2.3 to 4.2) had the lowest RR, whereas ketorolac (adj RR 14.4; 95% CI 5.2 to 39.9) had the highest. Rofecoxib treatment increased the risk of UGIB (adj RR 2.1; 95% CI 1.1 to 4.0), whereas celecoxib, paracetamol or concomitant use of a proton pump inhibitor with an NSAID presented no increased risk. Non-aspirin antiplatelet treatment (clopidogrel/ticlopidine) had a similar risk of UGIB (adj RR 2.8; 95% CI 1.9 to 4.2) to cardioprotective aspirin at a dose of 100 mg/day (adj RR 2.7; 95% CI 2.0 to 3.6) or anticoagulants (adj RR 2.8; 95% CI 2.1 to 3.7). An apparent interaction was found between low-dose aspirin and use of non-aspirin-NSAIDs, coxibs or thienopyridines, which increased further the risk of UGIB in a similar way. CONCLUSIONS: Coxib use presents a lower RR of UGIB than non-selective NSAIDs. However, when combined with low-dose aspirin, the differences between non-selective NSAIDs and coxibs tend to disappear. Treatment with either non-aspirin antiplatelet or cardioprotective aspirin has a similar risk of UGIB.

Double-blind investigation of the effects of propranolol and placebo on the pressure of esophageal varices in patients with portal hypertension.

This study was aimed at investigating the effects of propranolol on esophageal variceal pressure in patients with portal hypertension. Variceal pressure was measured at endoscopy using a miniature pressure-sensitive gauge in 20 patients with portal hypertension. Measurements were obtained under baseline conditions and 20 min after double-blind administration of propranolol (0.15 mg/kg; n = 10) or an identical amount of placebo (normal saline, 0.3 ml/kg; n = 10). Under baseline conditions, variceal pressure was similar in propranolol and placebo groups (14.1 +/- 5 mm Hg vs. 14.9 +/- 6.6 mm Hg, respectively; not significant). Placebo had no significant effect on variceal pressure (baseline = 14.9 +/- 6.6 mm Hg; placebo = 15.5 +/- 6.6 mm Hg; not significant), and values after placebo administration were closely correlated with baseline values (r = 0.98; y = 1.1 + 0.97 x; p less than 0.0001). In contrast, propranolol caused a significant decrease in the pressure of esophageal varices (from 14.1 +/- 5 mm Hg to 11.3 +/- 4.4 mm Hg; p less than 0.0002). No significant changes in the size of esophageal varices were observed after propranolol or placebo administration. This study shows (a) the endoscopic pressure-gauge technique has a low variability and may be used to assess acute drug-induced changes in variceal pressure; and (b) propranolol causes significant decreases in variceal pressure in patients with portal hypertension and esophageal varices.

Propranolol compared with propranolol plus isosorbide-5-mononitrate for portal hypertension in cirrhosis. A randomized controlled study.

OBJECTIVE: To investigate whether isosorbide-5-mononitrate (Is-5-Mn) given with propranolol reduces hepatic portal pressure more than does propranolol alone in patients with cirrhosis. DESIGN: A randomized controlled trial. PATIENTS: Fifty patients with cirrhosis and esophageal varices entered and 42 completed the study. INTERVENTION: Twenty-one patients received oral propranolol at increasing doses until their resting heart rate was reduced by 25%, and 21 patients received oral propranolol (on the same schedule) plus oral Is-5-Mn, 40 mg twice a day. MEASUREMENTS: Hepatic vein pressure gradient, liver function, and splanchnic and systemic hemodynamics before and after 3 months of continuous therapy. MAIN RESULTS: At 3 months, the hepatic venous pressure gradient decreased more (P less than 0.01) in patients given propranolol plus Is-5-Mn (19%, from 18.4 +/- 3.9 to 14.9 +/- 3.8 mm Hg; 95% CI, -2.4 to -4.5 mm Hg) than in those given propranolol alone (10%, from 18.2 +/- 3.5 to 16.3 +/- 3.1 mm Hg; CI, -1.1 to -2.7 mm Hg). The hepatic venous pressure gradient decreased by more than 20% of the baseline value in 10% of patients receiving propranolol, but in 50% of patients receiving combined therapy (P less than 0.02). There were statistically significant decreases in hepatic blood flow and the intrinsic clearance of indocyanine green after propranolol therapy, but not after combined therapy. The treatments caused similar reductions in azygos blood flow and cardiac output. CONCLUSIONS: The long-term combined administration of propranolol plus Is-5-Mn reduces portal pressure more than propranolol alone without adverse effects on hepatic perfusion and liver function. Whether this greater hemodynamic effect translates into better clinical efficacy should be determined in randomized controlled trials.

Pathophysiology of portal hypertension.

Portal hypertension is characterized by a pathologic increase in portal venous pressure that leads to the formation of an extensive network of portosystemic collaterals that divert a large fraction of portal blood to the systemic circulation, bypassing the liver. Experimental models have improved understanding of the pathophysiology of portal hypertension. It is now clear that an increased vascular resistance to portal blood flow is the initial factor responsible for the increase in portal pressure. This resistance is exerted along the hepatic and portal-collateral circulation and is in part modifiable by pharmacologic agents. In a latter stage, an increased portal venous blood inflow, promoted by splanchnic vasodilation, contributes to maintenance and aggravation of portal hypertension. Humoral vasodilatory agents play an important role in the splanchnic vasodilation. Several vasodilators are likely to be involved, including glucagon, prostacyclin, endotoxins, and nitric oxide. The splanchnic vasodilation is associated with a hyperkinetic systemic circulation, with reduced arterial pressure and peripheral resistance and increased cardiac output. The splanchnic circulation is probably the vascular territory in which the vasodilation is more pronounced. Therefore, splanchnic and systemic vasodilation probably share some pathophysiologic events. An expanded plasma volume is observed in all forms of portal hypertension. Expansion of plasma volume is due to renal sodium retention, which has been shown to precede the increase in cardiac output and can be prevented or reversed by sodium restriction and spironolactone. The expanded blood volume represents another mechanism that contributes to further increases in portal pressure.

Measurement of variceal pressure with an endoscopic pressure sensitive gauge: validation and effect of propranolol therapy in chronic conditions.

AIM/METHODS: Variceal pressure was measured at endoscopy in 98 patients with a non-invasive, pressure-sensitive gauge technique. RESULTS: In nine patients undergoing sclerotherapy, the values obtained correlated closely with those determined by fine-needle puncture of the varices (r = 0.95, p < 0.001). In 15 patients receiving placebo as part of a double-blind, placebo-controlled prospective evaluation of prophylactic treatment with propranolol, variceal pressure did not change significantly over a 1-year period: 16.5 +/- 3.2 mmHg at onset: 16.7 +/- 3.4 after 3 months and 15.9 +/- 3.5 after 12 months. In contrast, propranolol therapy given to 15 patients decreased the pressure from 16.2 +/- 3.0 mmHg before therapy to 13.5 +/- 2.0 after 3 months (p < 0.001) and to 13.1 +/- 4.1 after 12 months (p < 0.05). Patients with a recent bleeding episode had higher pressures than those who had not yet experienced any haemorrhage (19.3 +/- 3.5 mmHg, n = 17 vs 13.9 +/- 3.3, n = 62) (p < 0.001). This was confirmed in a prospective study: the last variceal pressure in bleeders and non-bleeders was respectively 17.2 +/- 1.7 mmHg (n = 4) and 14.8 +/- 4.1 mmHg (n = 26) (p < 0.01). Overall, variceal pressure measurements correlated with the size of varices, the presence of red colour signs and with the North Italian Endoscopic Club score. CONCLUSIONS: This study has shown that the non-invasive pressure gauge Varipress represents a reproducible method to regularly assess variceal pressure, an important parameter related to the risk of bleeding, and to assess the effects of pharmacological therapy with propranolol.