J. Balanzó

Controlled trial of tamoxifen in patients with advanced hepatocellular carcinoma

Thirty-six consecutive patients with advanced hepatocellular carcinoma and chronic liver disease were randomly allocated to two groups: group I included 20 patients who were treated with 10 mg bid. tamoxifen and group II with 16 non-treated patients. The two groups were homogeneous according to clinical and analytical data. Survival curves in the tamoxifen-treated patients improved significantly when compared with the non-treated group (p = 0.01). Cumulative survival at the end of the first year was 48.5% in the treated patients and 9.1% in controls. Median survival was 261 days in the treated group vs. 172 in the non-treated group (p < 0.05). Complications of cirrhosis and worsening of the performance status test occurred less in the treated patients than in the controls, but not significantly so. Tamoxifen was well tolerated and no marked side effects were observed. In this series, tamoxifen improved survival in patients with advanced hepatocellular carcinoma.

The detection of bacterial DNA in blood of rats with CCl4-induced cirrhosis with ascites represents episodes of bacterial translocation†

Bacterial DNA (bactDNA) is present in blood and ascitic fluid (AF) in a third of patients with cirrhosis and ascites, but whether this phenomenon represents episodes of bacterial translocation (BT), strictly considered when culture of mesenteric lymph nodes (MLNs) are positive, remains unknown. This study assessed the relationship between bactDNA detection in biological fluids and MLNs and went on to investigate the local and systemic inflammatory status according to its presence. Cirrhosis was induced in rats by ingestion of CCL4. A subgroup of five animals with cirrhosis received norfloxacin (5 mg/kg/day) for 7 days. MLNs and ascitic and pleural fluids were collected at laparotomy and cultured; samples were collected for identification of bactDNA and measurement of tumor necrosis factor‐alpha (TNF‐α), interleukin‐6 (IL‐6), and nitric oxide (NO). BactDNA was detected in MLNs in 12 of 19 animals (63.1%), corresponding in seven cases to culture‐positive MLNs, and in five to culture‐negative MLNs. BactDNA was detected in biological fluids in 11 of 19 animals (57.9%), and in all cases the same bacteria spp. detected in samples was present in MLNs. BactDNA was not detected in any biological sample from animals receiving norfloxacin. Tumor necrosis factor alpha (TNF‐α), IL‐6, and NO were similar in culture‐positive and culture‐negative/bactDNA‐positive samples, and significantly higher than those observed in animals with culture‐negative/bactDNA‐negative MLNs, animals with cirrhosis that were receiving norfloxacin, and controls. In conclusion, the presence of bactDNA in biological fluids in rats with cirrhosis constitutes a marker of BT, and it is associated with a marked inflammatory response, independent of the result of the culture. (HEPATOLOGY 2006.)

Intestinal mucosal oxidative damage and bacterial translocation in cirrhotic rats

Background Bacterial translocation plays an important role in the pathogenesis of spontaneous bacterial peritonitis mainly due to intestinal bacterial overgrowth. Alterations in the functional integrity of the intestinal barrier caused by an increased production of free radical metabolites as a consequence of portal hypertension could also facilitate bacterial translocation in cirrhotic rats. Objective The aim of the study was to determine intestinal mucosal lipid peroxidation and neutrophil infiltration and their relationship with portal hypertension and bacterial translocation in cirrhotic rats. Design Eighteen male Sprague–Dawley rats with cirrhosis induced by carbon tetrachloride, administered by gavage, and eight control rats were included in the study. Methods Samples of jejunum, ileum and caecum were obtained by laparotomy for the determination of malondialdehyde and myeloperoxidase as indexes of lipid peroxidation and neutrophil infiltration, respectively. Samples of ascitic and pleural fluids, mesenteric lymph nodes and ileal stools were obtained for the culture of microoganisms. Results The concentration of malondialdehyde was significantly higher in ileal and caecal, but not in jejunal mucosa, in cirrhotic rats, mainly in those with ascites (P < 0.01), as compared to control rats (P < 0.01), and in cirrhotic rats with bacterial translocation compared to those without bacterial translocation (P < 0.01). No differences between groups were observed in the concentrations of myeloperoxidase in jejunum, ileum or caecum. A direct correlation between ileal malondialdehyde and portal pressure was observed (P < 0.01). Conclusions Cirrhotic rats, particularly those with ascites and bacterial translocation, show increased malondialdehyde levels in ileal and caecal mucosa. These results suggest that mucosal oxidative damage in ileum and caecum could favour bacterial translocation in cirrhotic rats.

Systemic prostacyclin in cirrhotic patients: Relationship with portal hypertension and changes after intestinal decontamination

The total body production of prostacyclin was shown to be increased in cirrhotic patients, suggesting that its synthesis by blood vessels of the systemic circulation is enhanced. However, the mechanism by which the synthesis of systemic prostacyclin is stimulated is not known. The present study investigated the urinary excretion of 2,3-dinor-6-keto-PGF1 alpha, an index of total body prostacyclin synthesis, first, in cirrhotics with portal hypertension (n = 19) as compared with cirrhotics with reduced portal pressure after portacaval shunt surgery (n = 18) and with control noncirrhotic subjects (n = 11), and; second, in cirrhotics before and after intestinal decontamination by oral nonabsorbable antibiotics (n = 9 antibiotic treated patients, n = 10 control nontreated cirrhotics). Control noncirrhotic subjects showed lower urinary excretion of 2,3-dinor-6-keto-PGF1 alpha than both groups of cirrhotics (P less than 0.001). Interestingly, urinary excretion of 2,3-dinor-6-keto-PGF1 alpha was significantly higher in cirrhotics with portacaval shunt than in those with portal hypertension (P less than 0.01). The urinary excretion of 2,3-dinor-6-keto-PGF1 alpha decreased significantly after intestinal decontamination in the antibiotic-treated group (580.1 +/- 232.4 vs. 431.2 +/- 219.2 pg/mg creatinine; P less than 0.05) but not in nontreated patients (543.9 +/- 214.4 vs. 581.2 +/- 281.4 pg/mg creatinine; P = NS). These data suggest that the increased urinary excretion of 2,3-dinor-6-keto-PGF1 alpha observed in cirrhotics is not directly related to portal hypertension itself but to portal blood factors that bypass the liver. Some such factors may be of intestinal bacterial origin.

MRI pallidal hyperintensity and brain atrophy in cirrhotic patients Two different MRI patterns of clinical deterioration

In cirrhotic patients, even in a stable nonencephalopathic state, MRI may show cerebral atrophy and increased signal in globus pallidus on T1-weighted sequences. We investigated the relationship between cerebral atrophy and increased pallidal signal and the clinical status of 30 cirrhotic patients. We found a weak association between the two MRI findings. There were different patterns of clinical variables related to the imaging findings. Performance on motor tasks involving speed correlated with the pallidal signal and plasma ammonia levels but not with atrophy. Test results for memory and frontal-premotor function were associated with brain atrophy but not with the pallidal signal or with ammonia.

Expedited Publication 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 an 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. NEUROLOGY 1996;47: 1526-1530

Persistence of MRI hyperintensity of the globus pallidus in cirrhotic patients : a 2-year follow-up study

Article abstract—We investigated the long-term persistence and short-term stability of globus pallidus (GP) hyperintensity on T1--weighted MRI in 19 cirrhotic patients. After a mean interval of 25.8 months, the hyperintensity of the GP persisted in 17 patients. Hyperintensity disappeared in two patients with hepatocarcinoma, indicating that hyperintensity can revert to normal in circumstances other than liver transplants. Ten patients participated in a 6–month study with repeated evaluations of GP signal intensity, plasma ammonia levels, and selected neuropsychological tests. The GP signal was fairly stable during the follow-up, and the variables considered maintained significant relationships. GP hyperintensity appears as a stable indicator of the functional status of cirrhotic patients.

Systemic prostacyclin in cirrhotic patients

Abstract The total body production of prostacyclin was shown to be increased in cirrhotic patients, suggesting that its synthesis by blood vessels of the systemic circulation is enhanced. However, the mechanism by which the synthesis of systemic prostacyclin is stimulated is not known. The present study investigated the urinary excretion of 2,3-dinor-6-keto-PGF1 α , an index of total body prostacyclin synthesis, first, in cirrhotics with portal hypertension (n = 19) as compared with cirrhotics with reduced portal pressure after portacaval shunt surgery (n = 18) and with control noncirrhotic subjects (n = 11), and; second, in cirrhotics before and after intestinal decontamination by oral nonabsorbable antibiotics (n = 9 antibiotic treated patients, n=10 control nontreated cirrhotics). Control noncirrhotic subjects showed lower urinary excretion of 2,3-dinor-6-keto-PGF1 α than both groups of cirrhotics ( P α was significantly higher in cirrhotics with portacaval shunt than in those with portal hypertension ( P α decreased significantly after intestinal decontamination in the antibiotic-treated group (580.1 ± 232.4 vs. 431.2 ± 219.2 pg/mg creatinine; P P = NS ). These data suggest that the increased urinary excretion of 2,3-dinor-6-keto-PGF1 α observed in cirrhotics is not directly related to portal hypertension itself but to portal blood factors that bypass the liver. Some such factors may be of intestinal bacterial origin.

Abnormalities of the Bereitschaftspotential and MRI pallidal signal in non-encephalopathic cirrhotic patients

In cirrhotic patients, even in the non-encephalopathic state, MRI may show an increased signal in globus pallidus in T1-weighted sequences, the clinical significance of which is still poorly characterized. A dysfunction of the motor circuit of the basal ganglia might be predicted if the increased MRI signal expressed alterations in the globus pallidus activity. We compared the Bereitschaftspotential (BP) in 15 non-encephalopathic cirrhotic patients and 15 age-matched controls and found that the amplitude of the early component and the peak negativity of the BP before the electromyogram onset were significantly reduced in the patient group. The intensity of the pallidal signal was related to the plasma ammonia level but the amplitudes of the BP were not related to the pallidal signal or to ammonia. These findings indicate that a defective activity of the cortical areas implicated in the preparation of movement, not specifically related to the pallidal signal, can be present in cirrhotic patients, even in the non-encephalopathic state.

Tratamiento quirúrgico de la acalasia: estudio comparativo entre la cirugía abierta y la laparoscópica

Resumen Introduccion La miotomia quirurgica es una eficaz alternativa al tratamiento medico o endoscopico de la acalasia, especialmente en pacientes jovenes o ante la recidiva tras la dilatacion. Las caracteristicas tecnicas de la miotomia extramucosa tipo Heller (intervencion funcional, sobre una zona anatomica facilmente accesible por laparoscopia) ha modificado el abordaje quirurgico, proponiendose como una buena indicacion para el abordaje laparoscopico. 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 quirurgico de la acalasia, bien mediante abordaje abierto o laparoscopico Material y metodos Se han revisado los resultados postoperatorios inmediatos y a medio plazo de una serie de 31 pacientes intervenidos entre 1999 y 2000 con el diagnostico clinico, endoscopico y manometrico de acalasia. Se evaluo la sintomatologia pre y poscirugia mediante una puntuacion (DeMeester modificado: disfagia, pirosis, dolor y regurgitacion [puntuacion 0-3]), asi como la tasa de conversion, la morbimortalidad inmediata y a medio plazo, la estancia y el grado de satisfaccion de la intervencion (puntuacion 0-4) Resultados Trece pacientes fueron intervenidos de forma abierta (grupo I) y 18 por laparoscopia (grupo II). En todos ellos se efectuo una miotomia tipo Heller, asociado a una hemiplicatura anterior tipo Dor en 29 o posterior tipo Toupet en 2. Un paciente se convirtio a cirugia abierta y en otro fue imposible crear el neumoperitoneo por adherencias por cirugia previa. Un paciente intervenido previamente por via abierta fue reoperado por laparoscopia por recidiva de la acalasia. No existieron diferencias en la duracion de la intervencion (132 ± 29 frente a 140 ± 25 min; p: NS) ni en la morbilidad, aunque se observo una significativa reduccion de la estancia postoperatoria (7,7 ± 2 frente a 3,7 ± 1 dias; p Conclusion El abordaje laparoscopico mantiene las caracteristicas del tratamiento quirurgico convencional anadiendo las ventajas de una tecnica menos agresiva