Clinical trial: a randomized controlled study on prevention of variceal rebleeding comparing nadolol + ligation vs. hepatic venous pressure gradient-guided pharmacological therapy.

BACKGROUND: Hepatic venous pressure gradient (HVPG) monitoring of therapy to prevent variceal rebleeding provides strong prognostic information. Treatment of nonresponders to beta-blockers +/- nitrates has not been clarified. AIM: To assess the value of HVPG-guided therapy using nadolol + prazosin in nonresponders to nadolol + isosorbide-5-mononitrate (ISMN) compared with a control group treated with nadolol + ligation. METHODS: Cirrhotic patients with variceal bleeding were randomized to HVPG-guided therapy (n = 30) or nadolol + ligation (n = 29). A Baseline haemodynamic study was performed and repeated within 1 month. In the guided-therapy group, nonresponders to nadolol + ISMN received nadolol and carefully titrated prazosin and had a third haemodynamic study. RESULTS: Nadolol + prazosin decreased HVPG in nonresponders to nadolol + ISMN (P < 0.001). Finally, 74% of patients were responders in the guided-therapy group vs. 32% in the nadolol + ligation group (P < 0.01). The probability of rebleeding was lower in responders than in nonresponders in the guided therapy group (P < 0.01), but not in the nadolol + ligation group (P = 0.41). In all, 57% of nonresponders rebled in the guided-therapy group and 20% in the nadolol + ligation group (P = 0.05). The incidence of complications was similar. CONCLUSIONS: In patients treated to prevent variceal rebleeding, the association of nadolol and prazosin effectively rescued nonresponders to nadolol and ISMN, improving the haemodynamic response observed in controls receiving nadolol and endoscopic variceal ligation. Our results also suggest that ligation may rescue nonresponders.

Clinical trial: intravenous pantoprazole vs. ranitidine for the prevention of peptic ulcer rebleeding: a multicentre, multinational, randomized trial.

BACKGROUND: Controlled pantoprazole data in peptic ulcer bleeding are few. AIM: To compare intravenous (IV) pantoprazole with IV ranitidine for bleeding ulcers. METHODS: After endoscopic haemostasis, 1256 patients were randomized to pantoprazole 80 mg+8 mg/h or ranitidine 50 mg+13 mg/h, both for 72 h. Patients underwent second-look endoscopy on day 3 or earlier, if clinically indicated. The primary endpoint was an overall outcome ordinal score: no rebleeding, rebleeding without/with subsequent haemostasis, surgery and mortality. The latter three events were also assessed separately and together. RESULTS: There were no between-group differences in overall outcome scores (pantoprazole vs. ranitidine: S0: 91.2 vs. 89.3%, S1: 1.5 vs. 2.5%, S2: 5.4 vs. 5.7%, S3: 1.7 vs. 2.1%, S4: 0.19 vs. 0.38%, P = 0.083), 72-h clinically detected rebleeding (2.9% [95% CI 1.7, 4.6] vs. 3.2% [95% CI 2.0, 4.9]), surgery (1.9% [95% CI 1.0, 3.4] vs. 2.1% [95% CI 1.1, 3.5]) or day-3 mortality (0.2% [95% CI 0, 0.09] vs. 0.3% [95% CI 0, 1.1]). Pantoprazole significantly decreased cumulative frequencies of events comprising the ordinal score in spurting lesions (13.9% [95% CI 6.6, 24.7] vs. 33.9% [95% CI 22.1, 47.4]; P = 0.01) and gastric ulcers (6.7% [95% CI 4, 10.4] vs. 14.3% [95% CI 10.3, 19.2], P = 0.006). CONCLUSIONS: Outcomes amongst pantoprazole and ranitidine-treated patients were similar; pantoprazole provided benefits in patients with arterial spurting and gastric ulcers.

Tratamiento del episodio agudo de hemorragia digestiva varicosa / No disponible

No disponible

Uso de una `cápsula endoscópica' para el diagnóstico de fístulas aortoentéricas. A propósito de un caso / Use of capsule endoscopy in the diagnosis of aortoenteric fistulas. A case report

Introducción. Las fístulas aortoentéricas o las erosiones entericoprotésicas del territorio aórtico en los pacientes sépticos pueden ser difíciles de diagnosticar debido a su clínica, en ocasiones larvada e insidiosa, por lo que el diagnóstico temprano es una de las mejores garantías a la hora de establecer una terapia rápida y eficaz Varón de 66 años operado cinco años atrás de una derivación aortobifemoral por patología oclusiva aortoilíaca. Acude a nuestro centro por presentar un cuadro séptico con un gran absceso retroperitoneal detectado mediante una tomografía axial computarizada (TAC), que engloba la rama izquierda del injerto. Con la sospecha diagnóstica de fístula aortoentérica secundaria por decúbito del duodeno sobre el injerto, se realiza una exploración digestiva mediante el uso de una `cápsula endoscópica', que consiste en una cámara en color, encapsulada y desechable, que muestra imágenes compatibles con la visualización directa del injerto a través de la luz duodenal. El diagnóstico de una erosión entericoprotésica se confirma durante la cirugía, y se realiza una exéresis de la prótesis infectada con una ligadura del muñón aórtico, previa derivación extranatómica a xilobifemoral, con limpieza y drenaje del absceso retroperitoneal. Conclusión. Se considera el uso de la `cápsula endoscópica' como una opción válida y una posibilidad diagnóstica más en el manejo de fístulas aortoentéricas primarias y secundarias o de las erosiones entericoprotésicas, junto a la endoscopia clásica, cuando las lesiones asienten distalmente a la cuarta porción duodenal o cuando otras técnicas de imagen no sean concluyentes. (AU)

Tratamiento quirúrgico de la acalasia: estudio comparativo entre la cirugía abierta y la laparoscópica / Surgical treatment of achalasia: comparison between open and laparoscopic surgery

Introducción. La miotomía quirúrgica es una eficaz alternativa al tratamiento médico o endoscópico de la acalasia, especialmente en pacientes jóvenes o ante la recidiva tras la dilatación. Las características técnicas de la miotomía extramucosa tipo Heller (intervención funcional, sobre una zona anatómica fácilmente accesible por laparoscopia) ha modificado el abordaje quirúrgico, proponiéndose como una buena indicación para el abordaje laparoscópico. Sin embargo, no existen estudios comparativos sobre la eficacia entre ambos tipos de abordaje. Objetivo. Comparar los resultados inmediatos y a medio plazo tras el tratamiento quirúrgico de la acalasia, bien mediante abordaje abierto o laparoscópico. Material y métodos. Se han revisado los resultados postoperatorios inmediatos y a medio plazo de una serie de 31 pacientes intervenidos entre 1999 y 2000 con el diagnóstico clínico, endoscópico y manométrico de acalasia. Se evaluó la sintomatología pre y poscirugía mediante una puntuación (DeMeester modificado: disfagia, pirosis, dolor y regurgitación [puntuación 0-3]), así como la tasa de conversión, la morbimortalidad inmediata y a medio plazo, la estancia y el grado de satisfacción de la intervención (puntuación 0-4).Resultados. Trece pacientes fueron intervenidos de forma abierta (grupo I) y 18 por laparoscopia (grupo II). En todos ellos se efectúo una miotomía tipo Heller, asociado a una hemiplicatura anterior tipo Dor en 29 o posterior tipo Toupet en 2. Un paciente se convirtió a cirugía abierta y en otro fue imposible crear el neumoperitoneo por adherencias por cirugía previa. Un paciente intervenido previamente por vía abierta fue reoperado por laparoscopia por recidiva de la acalasia.No existieron diferencias en la duración de la intervención (132 ñ 29 frente a 140 ñ 25 min; p: NS) ni en la morbilidad, aunque se observó una significativa reducción de la estancia postoperatoria (7,7 ñ 2 frente a 3,7 ñ 1 días; p < 0,0001) y de la reanudación de la actividad normal (45 ñ 20 frente a 20 ñ 13 días; p < 0,002). Ambas técnicas fueron efectivas de forma similar en la reducción de la sintomatología de la acalasia, aunque el abordaje laparoscópico se acompañó de una mayor satisfacción estética (2,2 ñ 1,1 frente a 3,4 ñ 0,7; < 0,005).Conclusión. El abordaje laparoscópico mantiene las características del tratamiento quirúrgico convencional añadiendo las ventajas de una técnica menos agresiva (AU)

Isosorbide mononitrate in the prevention of first variceal bleed in patients who cannot receive beta-blockers.

BACKGROUND & AIMS: Nonselective beta-blockers (beta-blockers) are very effective in preventing first variceal bleeding (FVB) in patients with cirrhosis. However, 15%-25% of patients have contraindications or develop severe side effects precluding its use. The present study evaluates whether isosorbide-5-mononitrate (Is-MN) effectively prevents variceal bleeding in patients with contraindications or who could not tolerate beta-blockers. METHODS: One hundred thirty-three consecutive cirrhotic patients with gastro-esophageal varices and contraindications or intolerance to beta-blockers were included in a multicenter, prospective, double-blind randomized controlled trial. Sixty-seven were randomized to receive Is-MN, and 66 to receive placebo. RESULTS: There were no significant differences in the 1- and 2-year actuarial probability of experiencing a FVB between the 2 treatment groups. Presence of variceal red signs at endoscopy was the only variable independently associated with an increased risk of variceal bleeding on follow-up (relative risk 3.4; P < 0.01). Survival and adverse events were similar in the 2 groups. There were no significant differences in the incidence of ascites or changes in renal function. CONCLUSIONS: Is-MN does not reduce the incidence of FVB in patients with cirrhosis and esophageal varices who cannot be treated with beta-blockers because contraindications or intolerance to these drugs, suggesting that Is-MN has no place in the primary prophylaxis of variceal bleeding.

Endoscopic ligation compared with combined treatment with nadolol and isosorbide mononitrate to prevent recurrent variceal bleeding.

BACKGROUND: After an episode of acute bleeding from esophageal varices, patients are at high risk for recurrent bleeding and death. We compared two treatments to prevent recurrent bleeding--endoscopic ligation and combined medical therapy with nadolol and isosorbide mononitrate. METHODS: We randomly assigned 144 patients with cirrhosis who were hospitalized with esophageal variceal bleeding to receive treatment with endoscopic ligation (72 patients) or the combined medical therapy (72 patients). Sessions of ligation were repeated every two to three weeks until the varices were eradicated. The initial dose of nadolol was 80 mg orally once daily, with adjustment according to the resting heart rate; isosorbide mononitrate was given in increasing doses, beginning at 20 mg once a day at bed time and rising over the course of one week to 40 mg orally twice a day, unless side effects occurred. The primary end points were recurrent bleeding, complications, and death. RESULTS: The median follow-up period was 21 months. A total of 35 patients in the ligation group and 24 in the medication group had recurrent bleeding. The probability of recurrence was lower in the medication group, both for all episodes related to portal hypertension (P=0.04) and for recurrent variceal bleeding (P=0.04). There were major complications in nine patients treated with ligation (seven had bleeding esophageal ulcers and two had aspiration pneumonia) and two treated with medication (both had bradycardia and dyspnea) (P=0.05). Thirty patients in the ligation group died, as did 23 patients in the medication group (P=0.52). The probability of recurrent bleeding was lower for patients with a hemodynamic response to therapy, defined as a decrease in the hepatic venous pressure gradient of more than 20 percent from the base-line value or to less than 12 mm Hg (18 percent, vs. 54 percent in patients with no hemodynamic response at one year; P<0.001), and the probability of survival was higher (94 percent vs. 78 percent at one year, P=0.02). CONCLUSIONS: Combined therapy with nadolol and isosorbide mononitrate is more effective than endoscopic ligation for the prevention of recurrent bleeding and is associated with a lower rate of major complications. A hemodynamic response to treatment is associated with a better long-term prognosis.

Somatostatin treatment and risk stratification by continuous portal pressure monitoring during acute variceal bleeding.

BACKGROUND AND AIMS: During acute variceal bleeding, several factors may lead to elevations of hepatic venous pressure gradient (HVPG), which may precipitate further hemorrhage. Whether somatostatin can suppress these increments is unknown. This study monitored somatostatin effects on HVPG during acute bleeding and assessed whether the changes affect outcome. METHODS: In 40 patients with acute variceal bleeding treated with sclerotherapy, a catheter was placed into a main hepatic vein for 24-hour serial measurements of HVPG. After baseline measurements, patients received somatostatin (N = 25) or placebo (N = 15) under double blind conditions. RESULTS: Somatostatin but not placebo produced a sustained decrease in HVPG (from 20.7 +/- 3.7 mm Hg to 17.7 +/- 2.7, P < 0.01). In patients receiving placebo, HVPG increased after a test meal (P = 0.018) and after blood transfusion (P = 0.034). Somatostatin completely prevented these increments. HVPG decreased significantly only in patients without further bleeding. One of 27 patients with HVPG <20 mm Hg at baseline or decreased >10% rebled vs. 9 of 13 who had neither of these 2 criteria (P < 0.0001). Both criteria had independent prognostic value for further bleeding. CONCLUSIONS: During acute variceal bleeding, somatostatin produces a significant and sustained decrease in HVPG and prevents secondary elevations. Monitoring HVPG may stratify further bleeding risk and discriminate treatment response.

Relationship between cerebral perfusion in frontal-limbic-basal ganglia circuits and neuropsychologic impairment in patients with subclinical hepatic encephalopathy.

UNLABELLED: Early detection of neuropsychologic impairment in cirrhotic patients with subclinical hepatic encephalopathy (SHE) is important for their prognosis and quality of life. Abnormal MRI and MR spectroscopy (MRS) findings have been proposed as early markers of brain damage in these patients, but the role of functional neuroimaging in this field still has to be defined. In this study, the SPECT perfusion pattern in patients with SHE was investigated, and the relationship between regional cerebral blood flow (rCBF) and the MRI, MRS, neuropsychologic evaluation and biochemical data of these patients was assessed. METHODS: Data were obtained from 13 cirrhotic patients with SHE and 13 age-matched healthy volunteers. Fasting venous blood ammonia and manganese sampling and a battery of standardized neuropsychologic tests related to basal ganglia function and sensitive to the effects of liver disease were all performed on the same day. MRI and 99mTc-hexamethyl propyleneamine oxime SPECT were performed within 2 wk. RESULTS: A pattern of decreased prefrontal rCBF was found in patients with SHE compared with healthy volunteers. Basal ganglia and mesial temporal rCBF correlated inversely with performance on motor tasks involving speed (Purdue pegboard test) and frontal premotor function (Luria graphic alternances and Stroop tests). Thalamic rCBF correlated positively with T1-weighted MRI signal hyperintensity in the globus pallidus and with abnormal MRS findings. Neither the MRI signal intensity of the globus pallidus nor MRS correlated with neuropsychologic test results. CONCLUSION: Cirrhotic patients with SHE show a SPECT pattern of impaired prefrontal perfusion that does not seem to account for their neuropsychologic deficits. On the other hand, perfusion in some parts of the limbic system and limbic-connected brain regions, such as the striatum and the mesial temporal regions, increased with neuropsychologic impairment. These findings suggest that brain SPECT may be more sensitive than MRI in delineating cirrhotic patients requiring in-depth clinical testing to reveal basal ganglia-related neuropsychologic alterations.

Risk of a first community-acquired spontaneous bacterial peritonitis in cirrhotics with low ascitic fluid protein levels.

BACKGROUND & AIMS: Long-term primary antibiotic prophylaxis of spontaneous bacterial peritonitis has been suggested to be useful in cirrhotic patients with low ascitic fluid protein levels. However, it is unlikely that all such patients need prophylactic treatment. The aim of this study was to identify the group of cirrhotic patients with low ascitic fluid protein levels at high risk of developing a first episode of spontaneous bacterial peritonitis during outpatient follow-up. METHODS: One hundred nine cirrhotic patients with low ascitic fluid protein levels and without previous episodes of spontaneous bacterial peritonitis were followed up in an outpatient clinic. RESULTS: Twenty-eight patients developed a first spontaneous bacterial peritonitis episode. In the multivariate analysis, serum bilirubin level (>3.2 mg /dL) and platelet count (<98.000/mm(3)) independently correlated with the risk of developing the first spontaneous bacterial peritonitis (P < 0.01 and P < 0.05, respectively). According to the median relative risk coefficient, a low-risk group (relative risk <1.09) and a high-risk group (relative risk >1.09) were established. The probability of developing a first spontaneous bacterial peritonitis episode at 1-year follow-up was significantly higher in the high risk-group (low-risk group, 23.6%; high-risk group, 55%; P < 0.01) as a consequence of a higher probability of the first community-acquired episode (13.7% vs. 47.6%, respectively, P < 0.01). One-year probability of survival was significantly lower in the high-risk group (low-risk group, 57.6%; high-risk group, 38%, P < 0.05). CONCLUSIONS: Cirrhotic patients with low ascitic fluid protein levels (

Somatostatin alone or combined with emergency sclerotherapy in the treatment of acute esophageal variceal bleeding: a prospective randomized trial.

Recent trials have shown that somatostatin (SMT) is as effective as sclerotherapy in the treatment of acute variceal bleeding and that the combination of both treatments is more effective than sclerotherapy alone. To assess whether the addition of sclerotherapy improves the efficacy of SMT alone, all patients admitted to our unit with gastrointestinal bleeding and with suspected cirrhosis received a continuous infusion of SMT (250 micrograms/h). Endoscopy was performed between 1 and 5 hours later, and patients with esophageal variceal bleeding were randomized to receive or not to receive sclerotherapy. In both groups, SMT infusion was continued for 5 days. Fifty patient admissions were allocated to each group. Therapeutic failure occurred in 21 cases of the SMT group and in 7 cases of the combined-therapy group (P =.002). Failure to control the acute episode occurred in 24% vs. 8% (P =.03) and early rebleeding in 24% vs. 7% (P =.03), respectively. Transfusional requirements were significantly higher in the SMT group, while the incidence of complications was lower (8% vs. 24%; P =.029). In the multivariate analysis, the presence of shock at admission and active bleeding during endoscopy were the variables that better predicted the failure of therapy with SMT alone. Mortality at 6 weeks was similar. These data demonstrate that the addition of sclerotherapy significantly improves the efficacy of SMT alone for the treatment of acute variceal bleeding, although it also increases the rate of complications. Patients with shock and those with active bleeding are more likely to benefit from this combined therapy.

Parenteral antibiotic prophylaxis of bacterial infections does not improve cost-efficacy of oral norfloxacin in cirrhotic patients with gastrointestinal bleeding.

OBJECTIVE: Selective intestinal decontamination with norfloxacin is useful in the prevention of bacterial infections in cirrhotic patients with gastrointestinal bleeding. However, bleeding cirrhotic patients with ascites, encephalopathy, or shock are at high risk to develop bacterial infections in spite of prophylactic norfloxacin. The aim of this study was to assess whether the addition of intravenous ceftriaxone could improve the efficacy of prophylaxis with norfloxacin in these patients. METHODS: Fifty-six cirrhotic patients with gastrointestinal hemorrhage and ascites, encephalopathy, or shock were randomized into two groups: Group 1 (n = 28) received oral norfloxacin 400 mg/12 h for 7 days, and group 2 (n = 28) received norfloxacin plus intravenous ceftriaxone 2 g daily during the first 3 days of admission. RESULTS: Ten patients were excluded because of community-acquired infection, surgery, or death within the first 24 h. The incidence of bacterial infections during hospitalization was 18.1% in group 1 and 12.5% in group 2 (p = NS). The incidence of severe infections (spontaneous bacterial peritonitis, bacteremia, or pneumonia) was also similar in both groups: 9% in group 1 versus 8.3% in group 2 (p = NS). There were no statistical differences between the two groups with respect to duration of hospitalization or mortality. The cost of antibiotic therapy (including prophylaxis and treatment of infections) was significantly higher in group 2. CONCLUSION: These results suggest that the addition of intravenous ceftriaxone during the first 3 days of hospitalization does not improve the cost-efficacy of oral norfloxacin in the prevention of bacterial infections in cirrhotic patients with gastrointestinal bleeding and high risk of infection.

Effect of subcutaneous administration of octreotide on endogenous vasoactive systems and renal function in cirrhotic patients with ascites.

Splanchnic and systemic arteriolar vasodilation plays an important role in ascites formation in cirrhosis. Octreotide produces splanchnic vasoconstriction, but the effects on systemic hemodynamics and renal function are controversial. This study evaluated the effect of subcutaneous octreotide administration on systemic hemodynamics, endogenous vasoactive systems, and renal function in cirrhotic patients with ascites. Twenty patients were included: 10 received octreotide 250 microg/12 hr subcutaneously (for five days), and 10 did not. No statistically significant changes were found in mean arterial pressure and cardiac rate. Octreotide induced a statistically significant decrease in plasma renin activity (P < 0.01), plasma aldosterone (P = 0.01) and plasma glucagon (P < 0.05). No significant variations were observed in other systemic vasoactive substances (nitric oxide and prostacyclin). Renal function was not modified in either group. In conclusion, in cirrhotic patients with ascites, subcutaneous octreotide administration decreases plasma glucagon, renin activity, and aldosterone without changing in systemic hemodynamics or renal function.

A practical guide to the management of bleeding ulcers.

In patients with acute haemorrhage from peptic ulcers, emergency endoscopy should be performed as soon as safely possible after resuscitation to detect the bleeding lesion, to define stigmata of recent haemorrhage, and to perform endoscopic therapy when required. Subsequent management will be determined by the results of diagnostic endoscopy. Ulcers with a clean base or with flat blood spots will not require endoscopic therapy: the patient can be discharged early after resuscitation and the institution of treatment to promote ulcer healing. Ulcers in which endoscopy discloses active arterial bleeding or a nonbleeding visible vessel should be treated, as these signs denote a high risk of an unfavourable outcome, and the efficacy of endoscopic therapy has been demonstrated when these signs are identified. In keeping with the available data, antisecretory therapy, vasoconstrictor drugs and tranexamic acid cannot be recommended as treatment for an acute ulcer bleeding episode. On the other hand, it has been shown in controlled trials that endoscopic therapy significantly reduces the incidence of further bleeding and the requirement for emergency surgery in patients with ulcers with active arterial bleeding or a nonbleeding visible vessel. Meta-analyses of these studies have also shown a significant decrease in mortality with endoscopic therapy. Among the available endoscopic methods for haemostasis, injection therapy is a valid choice since its efficacy has been similar to that of thermal methods in comparative studies, while its simplicity, tolerability and low cost are great advantages. A second endoscopic treatment can be attempted in patients with further haemorrhage after the initial endoscopic therapy, and permanent haemostasis can be achieved in half of these cases. However, the decision to perform this second endoscopic treatment should be taken individually, as the routine use of such a procedure could increase mortality by delaying surgery.

Neurospectroscopic alterations and globus pallidus hyperintensity as related magnetic resonance markers of reversible hepatic encephalopathy.

In patients with chronic hepatic encephalopathy, proton magnetic resonance spectroscopy can be used to detect specific metabolic abnormalities in the brain; MRI shows a hyperintense globus pallidus on T1-weighted sequences. We investigated the relationship between these two MR findings in a series of 25 patients with the use of quantitative data and a multiple regression analysis model. The cerebral increase in glutamine compounds and the decrease in myoinositol and choline correlated separately with globus pallidus hyperintensity, and each was complementary in accounting for this imaging finding. Such as association suggests that spectroscopic and imaging alterations are two different expressions of the reversible events that occur in the brain of patients with hepatic encephalopathy in that both disappear after liver transplantation. Globus pallidus hyperintensity seems to be a global indicator of the cerebral metabolic disorder, and the spectroscopic pattern denotes the specific metabolic alterations.