Endoscopic prophylaxis and factors associated with bleeding in children with extrahepatic portal vein obstruction / Profilaxia endoscópica e fatores associados ao sangramento em crianças com obstrução extra-hepática da veia porta

Abstract Objectives: This study aimed to evaluate factors associated with upper digestive hemorrhage and primary and secondary endoscopic prophylaxis outcomes in children with extrahepatic portal vein obstruction. Methods: This observational and prospective study included 72 children with extrahepatic portal vein obstruction who were followed from 2005 to 2017. Risk factors associated with upper digestive hemorrhage and the results of primary and secondary prophylaxis of these patients were evaluated. Results: Fifty patients (69.4%) had one or more episodes of bleeding during follow-up, with a median age at first hemorrhage of 4.81 years. The multivariate analysis showed that medium- to large-caliber esophageal varices were associated with an 18-fold risk of upper digestive hemorrhage (95% CI: 4.33-74.76; p < 0.0001). Primary prophylaxis was administered to 14 patients, with eradication in 85.7%; however, 14.3% of these patients had hemorrhages during the follow-up period and 41.7% had a relapse of varices. Secondary prophylaxis was administered to 41 patients. Esophageal varices were eradicated in 90.2% of patients. There were relapse and re-bleeding of esophageal varices in 45.9% and 34.1% of the children, respectively. Conclusion: Primary and secondary endoscopic prophylaxes showed high rates of esophageal varix eradication, but with significant relapses. Eradication of esophageal varices cannot definitively prevent recurrent upper digestive hemorrhage, since bleeding from alternate sites can occur. Medium- and large-caliber esophageal varices were associated with upper digestive hemorrhage in patients with extrahepatic portal vein obstruction. To the best of the authors' knowledge, this study is the first to evaluate bleeding risk factors in children with extrahepatic portal vein obstruction.

Resumo Objetivos: Este estudo visou avaliar fatores associados à hemorragia digestiva alta e resultados da profilaxia endoscópica primária e secundária em crianças com obstrução extra-hepática da veia porta. Métodos: Este estudo observacional e prospectivo incluiu 72 crianças com obstrução extra-hepática da veia porta acompanhadas de 2005 a 2017. Os fatores de risco associados à hemorragia digestiva alta e os resultados da profilaxia primária e secundária desses pacientes foram avaliados. Resultados: Dos pacientes, 50 (69,4%) apresentaram ≥ 1 episódio de sangramento durante o acompanhamento, com idade média da primeira hemorragia de 4,81 anos. A análise multivariada mostrou que varizes esofágicas de médio a grande calibre estavam associadas a um risco 18 vezes maior de hemorragia digestiva alta (IC de 95% 4,33-74,76; p < 0,0001). Foi administrada profilaxia primária em 14 pacientes, com erradicação em 85,7%; contudo, 14,3% desses pacientes apresentaram hemorragias durante o período de acompanhamento e 41,7% apresentaram recidiva de varizes. Foi administrada profilaxia secundária em 41 pacientes. As varizes esofágicas foram erradicadas em 90,2% dos pacientes. Houve recidiva e novos sangramentos de varizes esofágicas em 45,9% e 34,1% das crianças, respectivamente. Conclusão: As profilaxias esofágicas primárias e secundárias apresentaram altas taxas de erradicação de varizes esofágicas, porém com recidivas significativas. A erradicação de varizes esofágicas não pode prevenir de forma definitiva a hemorragia digestiva alta recorrente, pois pode ocorrer sangramento de outros locais. Varizes esofágicas de médio e grande calibre estavam associadas à hemorragia digestiva alta em pacientes com obstrução extra-hepática da veia porta. No melhor de nosso conhecimento, nosso estudo é o primeiro a avaliar os fatores de risco de sangramento em crianças com obstrução extra-hepática da veia porta.

Carvedilol as primary prophylaxis for gastric variceal bleeding in portal hypertension model in rats / Carvedilol como profilaxia de sangramento em varizes gástricas em modelo de hipertensão portal em ratos

ABSTRACT Background: Portal hypertension (PH) can be measured indirectly through a hepatic vein pressure gradient greater than 5 mmHg. Cirrhosis is the leading cause for PH and can present as complications ascites, hepatic dysfunction, renal dysfunction, and esophagogastric varices, characterizing gastropathy. Aim: To evaluate the use of carvedilol as primary prophylaxis in the development of collateral circulation in rats submitted to the partial portal vein ligament (PPVL) model. Method: This is a combined qualitative and quantitative experimental study in which 32 Wistar rats were divided into four groups (8 animals in each): group I - cirrhosis + carvedilol (PPVL + C); group II - cirrhosis + vehicle (PPVL); group III - control + carvedilol (SO-sham-operated + C); group IV - control + vehicle (SO-sham-operated). After seven days of the surgical procedure (PPVL or sham), carvedilol (10 mg/kg) or vehicle (1 mL normal saline) were administered to the respective groups daily for seven days. Results: The histological analysis showed no hepatic alteration in any group and a decrease in edema and vasodilatation in the PPVL + C group. The laboratory evaluation of liver function did not show a statistically significant change between the groups. Conclusion: Carvedilol was shown to have a positive effect on gastric varices without significant adverse effects.

RESUMO Racional: A hipertensão portal (HP), medida indiretamente através do gradiente pressórico da veia hepática >5 mmHg, tem como principal causa etiológica a cirrose. Possui como complicações a ascite, disfunção hepática, disfunção renal e varizes esofagogástricas, que caracterizam o quadro de gastropatia. Objetivo: Avaliar o uso do carvedilol como profilaxia primária no desenvolvimento da circulação colateral em ratos submetidos ao modelo de ligadura parcial de veia porta (LPVP). Método: Estudo experimental qualitativo e quantitativo no qual foram utilizados 32 ratos Wistar, divididos em quatro grupos (n=8): grupo I - cirrose + carvedilol (LPVP+C); grupo II - cirrose + veículo (LPVP); grupo III - controle + carvedilol (SO - sham-operated+C); grupo IV - controle + veículo (SO - sham-operated). Após transcorridos sete dias do procedimento cirúrgico, foi administrado carvedilol (10 mg/kg) e veículo (1mL) para os respectivos grupos por sete dias consecutivos. Resultados: A análise histológica não mostrou alteração hepática em nenhum grupo e diminuição de edema e vasodilatação no grupo LPVP+C. A avaliação laboratorial da função hepática não mostrou alteração com significância estatística entre os grupos. Conclusão: Carvedilol mostrou ser fármaco com efeito positivo no sangramento das varizes gástricas e sem efeitos adversos significantes.

Evaluation of primary prophylaxis with propranolol and elastic band ligation in variceal bleeding in cirrhotic children and adolescents / Avaliação da profilaxia primária em crianças e adolescentes cirróticos com propranolol e ligadura elástica

ABSTRACT Background The efficacy of nonselective β-blocker and endoscopic procedures, such as endoscopic variceal ligation, as primary prophylaxis of variceal hemorrhage in cirrhotic adults was demonstrated by numerous controlled trials, but in pediatric population, few are the number of studies. Objective The objective of this study is to evaluate the primary prophylaxis with β-blocker in cirrhotic children and adolescents with portal hypertension. Methods This is a cohort study encompassing 26 cirrhotic patients. β-blocker prophylaxis was performed with propranolol. When contraindicated the use of β-blocker, or if side effects presents, the patients were referred to endoscopic therapy with band ligation. Patients were evaluated by endoscopy, and those who had varicose veins of medium and large caliber or reddish spots, regardless of the caliber of varices, received primary prophylaxis. Results Of the 26 patients evaluated, 9 (34.6%) had contraindications to the use of propranolol and were referred for endoscopic prophylaxis. Six (35.3%) of the 17 patients who received β-blocker (propranolol), had bled after a median follow-up time of 1.9 years. β-blockage dosage varied from 1 mg/kg/day to 3.1 mg/kg/day and seven (41.2%) patients had the propranolol suspended due to fail of the β-blockage or adverse effects, such as drowsiness, bronchospasm and hypotension. Patients who received endoscopic prophylaxis (elastic bandage) had no bleeding during the follow-up period. Conclusion All of the patients that had upper gastroinstestinal bleeding in this study were under propranolol prophylaxis. The use of propranolol showed a high number of contraindications and side effects, requiring referral to endoscopic prophylaxis. The endoscopic prophylaxis was effective in reducing episodes of bleeding.

RESUMO Contexto A eficácia dos beta-bloqueadores e de procedimentos endoscópicos como a ligadura elástica endoscópica para profilaxia primária de ruptura de varizes de esôfago em adultos cirróticos já foram demonstrados por inúmeros ensaios clínicos na população adulta, porém poucos são os estudos envolvendo a faixa etária pediátrica. Objetivo Avaliar a profilaxia primária com β-bloqueador em crianças e adolescentes cirróticos com hipertensão porta. Métodos Estudo de coorte envolvendo 26 pacientes cirróticos. O propranolol foi o β-bloqueador utilizado para a profilaxia. Quando contraindicado o uso de β-bloqueador, ou se efeitos colaterais presentes, os pacientes eram encaminhados para profilaxia endoscópica com ligadura elástica. Os pacientes foram avaliados por endoscopia, e naqueles que foram observadas varizes de médio e/ou grosso calibre ou presença de manchas avermelhadas nas varizes, independentemente do calibre das varizes, a profilaxia primária foi indicada. Resultados Dos 26 pacientes avaliados, 9 (34,6%) tinham contraindicações para o uso de propranolol e foram encaminhados para a profilaxia endoscópica. Seis (35,3%) dos 17 pacientes que receberam β-bloqueador (propranolol) apresentaram sangramento após mediana de tempo de acompanhamento de 1,9 anos. A dose de β-bloqueio variou de 1 mg/kg/dia a 3,1mg/kg/dia e em sete (41,2%) pacientes o propranolol foi suspenso por falha em atingir β-bloqueio ou presença de efeitos adversos, tais como sonolência, broncoespasmo e hipotensão. No grupo de pacientes que receberam a profilaxia endoscópica (ligadura elástica) não foi observado nenhum episódio de hemorragia digestiva alta durante o período de acompanhamento. Conclusão Todos os pacientes que apresentaram hemorragia digestiva alta no presente estudo estavam recebendo profilaxia com propranolol. Foi observado, ainda, elevado número de contraindicações e efeitos colaterais, com consequente encaminhamento para profilaxia endoscópica. A profilaxia endoscópica foi eficaz na redução de episódios de hemorragia digestiva alta.

Cirrosis hepática: medidas preventivas de algunas de sus complicaciones / Liver cirrhosis: some complications preventive measures

Cirrosis hepática es una enfermedad prevalente en el mundo. Su diagnóstico y tratamiento debe ser dominio de todo médico general e internista. En los últimos años han ocurrido notables avances en el diagnóstico, fisiopatología, tratamiento y en la identificación de factores pronósticos de cirrosis y de sus complicaciones mayores. Particular atención ha existido en desarrollar medidas preventivas de sus complicaciones como por ejemplo: hemorragia por várices esofágicas, peritonitis bacteriana espontánea, síndrome hepatorrenal. Estas medidas preventivas han influido de forma muy favorable en el pronóstico de los pacientes cirróticos. En este artículo se discuten las diversas estrategias preventivas que han demostrado su efectividad en cirrosis hepática

Liver cirrhosis is a prevalent disease around the world. Its diagnosis and treatment must be in the knowledge of every general physicians and internist.Over the last years, there have been notorious advances in the diagnosis, pathophysiology, treatment and the identification of prognosis factors for cirrhosis major complications.There has been particular attention to the development of preventive measures for its complications, such as variceal bleeding, spontaneous bacterial peritonitis, hepatorenal syndrome. These preventive measures have had a favorable influence on the prognosis of cirrhotic patients. This article discusses several preventive strategies that have proven its effectiveness in hepatic cirrhosis

Diagnóstico y tratamiento de las várices esófago gástricas en Chile: realidad nacional / Management of bleeding esophageal varices in public and private institutions in Chile

Background: The better treatment modalities for bleeding esophageal varices have improved the prognosis of cirrhosis. Aim: To inquire about diagnostic and treatment modalities for esophageal bleeding in Chile. Material and methods: An enquiry about diagnosis and treatment of esophageal bleeding was designed and electronically sent to public and private health institutions that could admit patients and were located in cides with more than 100,000 inhabitants. Results: The enquiry was answered by 31 of 35 public and 17 of 19 private health institutionis that were consulted. Emergency endoscopy was available in 6 of 27 public and in the 16 private institutionis that had an emergency room. Rubber band ligation was available in 16 public (52 percent) and in all private institutions. Cyanoacrylate injections were done in 10 public (32 percent) and 11 (65 percent) private institutions. No public institution installed transjugular intrahepatic portosystemic shunts, but 8 had occasional access to this technique. This procedure was done in 7 (41 percent) private institutions and all had access to it. Surgical treatment was feasible in 20 public (65 percent) and all private institutions. Primary prophylaxis was done in 18 public (58 percent) and 14 private (82 percent) institutions. Secondary prophylaxis was carried out in 26 public (84 percent) and 16 private (94 percent) institutions. Conclusions: Public health institutions have poor access to adequate diagnostic and treatment methods for esophageal bleeding. The primary and secondary prophylaxis of esophageal varices must be improved in both types of institutions.

Effect of band ligation on portal hypertensive gastropathy and development of fundal varices

Use of endoscopic therapies for esophageal varices has resulted in increased prevalence of fundal varices and severe portal hypertensive gastropathy. This study was meant to compare the effect of band ligation and sclerotherapy on development of fundal varices and portal hypertensive gastropathy. Patients with esophageal varices presenting in the endoscopy unit of Shiakh Zayed Hospital, with at least one previous endoscopy were included. Patient's past record was reviewed for findings and type of treatment given for varices during first endoscopy, number of endoscopies till date, number of esophageal varices band ligation [EVBL] or sclerotherapy sessions. All patients underwent upper GI endoscopy and findings were recorded. Type of treatment patient rendered during first endoscopy either EVBL or sclerotherapy was correlated to the presence of fundal varices and severity of portal hypertensive gastropathy observed on present endoscopy, using Chi square test [chi [2]]. Eighty one patients were included. Mean age of patients was 48.7 +/- 12.63. Esophageal varices band ligation was carried out during first endoscopy in 49 [60.5%] patients and sclerotherapy in 31 [38.2%] patients. On fresh endoscopy, fundal varices were seen in 25 [30.8%] patients. Severe portal hypertensive gastropathy was found in 26 [32.1%] and mild in 54 [66.7%] patients. Severity of portal hypertensive gastropathy and presence of fundal varices in recent endoscopy was significantly more in patients with EVBL in first endoscopy. Band ligation of esophageal varices is associated with more frequent development of fundal varices and worsening of portal hypertensive gastropathy compared to sclerotherapy

Prophylactic surgery in non-cirrhotic portal fibrosis:is it worthwhile?

BACKGROUND: In cirrhotic patients with portal hypertension prophylactic portasystemic shunts have been found to be ineffective as deaths from post-shunt liver failure exceed those from bleeding. However, in patients with non-cirrhotic portal hypertension, variceal bleeding rather than liver failure is the common cause of death. In developing countries shortage of tertiary health-care facilities and blood banks further increases mortality due to variceal bleed. AIM: To study the results of prophylactic operations to prevent variceal bleeding in patients with portal hypertension due to non-cirrhotic portal fibrosis (NCPF). METHODS: Between 1976 and 2001, we performed 45 prophylactic operations in patients with NCPF, if the patients had high-risk esophagogastric varices or symptomatic splenomegaly and hypersplenism. Proximal lienorenal shunt was done in 41 patients and the remaining underwent splenectomy with (2 patients) or without (2 patients) devascularization. RESULTS: There was no operative mortality. Thirty-eight patients were followed up for a mean 49 (range, 12-236) months. Three patients bled - one was variceal and two due to duodenal ulcers; none died of bleeding. There were 2 late deaths (6 weeks and 10 years after surgery), one from an unknown cause and one due to chronic renal failure. The delayed morbidity was 47%. This included 7 patients who developed portasystemic encephalopathy, 4 glomerulonephritis, 2 pulmonary arteriovenous fistulae and 5 ascites requiring treatment with diuretics. Thus only 20 (53%) patients were symptom-free on follow up. CONCLUSIONS: Prophylactic surgery is safe and effective in preventing variceal bleeding in NCPF but at the cost of high delayed morbidity.

Hemodynamic effect of spironolactone in liver cirrhosis and propranolol-resistant portal hypertension.

OBJECTIVE: In a proportion of patients with liver cirrhosis, portal pressure does not decrease adequately with propranolol. These patients may benefit from another drug that may reduce portal pressure. We evaluated the role of spironolactone, alone or with propranolol, in such patients. METHODS: Patients with cirrhosis, with or without ascites, with esophageal varices and with hepatic venous pressure gradient exceeding 12 mmHg, which did not show a 20% reduction after an 80-mg oral dose of propranolol, were studied. They were allocated to receive spironolactone 100 mg orally once daily either alone (group 1, n=10) or with propranolol 40 mg orally twice daily (group 2, n=10), for 7 days, after which the hemodynamic study was repeated. RESULTS: Hepatic venous pressure gradient decreased in those receiving spironolactone and propranolol (p=0.007); 5 patients in group 1 and 7 in group 2 showed a reduction in hepatic venous pressure gradient by more than 20%. However, the reduction produced by spironolactone alone (20.5 [31.3]%) was not significantly different from that produced by combination therapy (30.3 [25.9]%; p=0.46). CONCLUSION: Spironolactone in combination with propranolol achieves adequate reduction (> or = 20%) in hepatic venous pressure gradient in propranolol-resistant portal hypertension in patients with liver cirrhosis. Spironolactone alone was also effective in some patients.

Esophago-gastric dissociation complicating devascularization procedure for portal hypertension.

Devascularization surgery for portal hypertension, indicated in selected patients, is considered safe. A 15-year-old boy with cirrhosis underwent elective modified Sugiura's devascularization procedure for secondary prophylaxis of variceal bleeding. He developed esophago-gastric dissociation, which was successfully managed with emergency feeding jejunostomy and restoration of gut continuity three months later.

Hemorragia por várices esofágicas. Alternativas actuales de tratamiento / Esophageal variceal bleeding. Current treatment options

El manejo de la hemorragia secundaria a várices esofágicas continúa evolucionando. Contando con un mayor número de opciones de tratamiento, el reto es proporcionar las más óptimas. El único tratamiento profiláctico aceptado hasta la fecha es el farmacológico. El manejo del episodio agudo requiere instalar de inmediato adecuadas medidas de reanimación y manejo específico que incluye tratamiento farmacológico y endoscópico. Hay un papel muy limitado para procedimientos de descompresión en el episodio agudo de hemorragia. La prevención de hemorragia recurrente incluye varias fases de tratamiento: tratamiento farmacológico, endoscópico o ambos, procedimientos de descompresión y trasplante hepático. El manejo de la hemorragia secundaria a várices esofágicas requiere una estrecha colaboración y coordinación de un equipo multidisciplinario.

Hemorragia digestiva alta / Upper gastrointestinal bleeding

El autor efectua una revisión de la literatura sobre un problema frecuente en la práctica médica como lo es la Hemorragia Digestiva Alta, teniendo en consideración la etiología, la patogenia, la epidemiologia de la misma. Realiza una actualización de los métodos diagnósticos que han modificado los conceptos sobre las variables etiológicas. Asi mismo, efectua una evaluación de los medios terapeuticos generales y particulares considerando el manejo hemodinamico, la farmacología empleada en la actualidad y las indicaciones quirurgicas, haciendo enfasis en la importancia de la terapeutica endoscopica mediante la electrocoagulación, la sonda térmica y la escleroterapia que adquiere importancia por los costos reducidos del instrumental utilizado y la eficacia de la misma, presentando cifras estadísticas internacionales y locales. Efectua consideraciones sobre la prevención de la HDA cuando los pacientes requieren terapia con AINES y en los casos de stress fisiológico

Ranitidine for the prevention of complications following endoscopic sclerotherapy for esophageal varices.

Thirty one patients with significant esophageal variceal bleed were allocated alternately to receive endoscopic sclerotherapy along with ranitidine 300 mg daily or endoscopic sclerotherapy alone till eradication of varices. The mean sclerotherapy sessions, time and volume of sclerosant required for obliteration of varices were similar for the two groups. The esophageal varices were eradicated in all the patients except three in sclerotherapy alone group. There was statistically significant reduction in frequency of post sclerotherapy mucosal ulcers (P < 0.05) after addition of ranitidine to sclerotherapy. Rebleeding was not only significantly reduced (P < 0.05) in the sclerotherapy with ranitidine group but was minor and did not even require blood transfusion. In sclerotherapy alone group rebleeding was controlled by surgery in two patients and one died due to massive bleeding. The results of this study suggest a beneficial role of ranitidine in reducing post sclerotherapy mucosal ulcers and rebleeding. This effect of ranitidine emphasises the role of acid-pepsin in pathogenesis of these ulcers and its associated morbidity.