Papilomatosis esofágica: a propósito de un caso / Esofagic Papilomatosis / in relation to a case

Los tumores benignos del esófago son raros, constituyendo solo el 0,5 al 0,8 por ciento de todos los tumores esofágicos. Aproximadamente el 60 por ciento de los tumores benignos del esófago son leiomiomas, el 20 por ciento son quistes y el 5 por ciento son pólipos. El resto de las lesiones ocurren con una frecuencia menor del 2 por ciento y constituyen curiosidades y dentro de ellas tenemos al papiloma. Los papilomas son tumores benignos fibrosos y sésiles cubiertos por epitelio escamoso producidos por el papilomavirus humano (VPH), que tienen la capacidad de producir lesiones proliferativas en piel y/o mucosas. En el tubo digestivo se localizan más frecuentes hacia los extremos proximales (boca) y dístales (recto). El caso que se presentó se trata de una localización esofágica distal en un paciente de 49 años de edad, masculino, con sintomatología sugestiva de una enfermedad por reflujo gastroesofágico y/o un trastorno de la motilidad esofágica, diagnosticándosele -por endoscopia y biopsia- lesiones elevadas esofágicas y la presencia de coilocitos. Se le indicó tratamiento con interferón alfa 2 recombinante, quedando pendiente de evolución endoscópica e histológica post-tratamiento.

The benign tumors of the esophagus are rare, being only the 0,5-0,8 percent of all the esophageal tumors. Around the 60 percent of the benign esophageal tumors are leiomyomas, 20 percent are cists and 5 percent are polyps. The rest of the lesions occur with a frequency less than 2 percent being curiosities, and among them there is the papilloma. The papilloma are benign, fibrous and sessile tumors covered by a squamous epithelium produced by the human papilloma virus (HPV), having the capacity of producing proliferative lesions in the skin and/or mucosa. In the digestive tract they are more frequently located to the proximal (mouth) and distal (rectum) endings. In the case we present, it is a distal esophageal location in a male patient aged 49, with symptoms suggesting a disease by gastro-esophageal reflux and/or disturbances of the esophageal motility, arriving to the diagnosis by endoscopy and biopsy: elevated esophageal lesions and the presence of koilocytes. We indicated a treatment with Recombinant Alpha 2 Interferon, being pending the post-treatment endoscopic and histological evolution.

Avaliação tireoidiana de pacientes infectados pelo vírus da hepatite C: correlação com polimorfismos do gene CTLA4 / Thyroid evaluation of patients infected by hepatitis C virus: correlation with polymorphisms of CTLA4 gene

INTRODUÇÃO: Manifestações auto-imunes são frequentes na infecção pelo vírus da hepatite C (VHC). Apesar da associação com doenças auto-imunes de tireóide (DAIT) ser controversa, sabe-se que distúrbios tireoidianos podem surgir ou piorar com tratamento com IFN e ribavirina. Os objetivos deste estudo foram avaliar a função tireoidiana em pacientes infectados pelo VHC, caracterizar distúrbios tireoidianos antes, durante e após tratamento com IFN e estudar as frequências dos genótipos dos polimorfismos do gene CTLA4, correlacionando-os com características clínicas e laboratoriais, presença de disfunção tireoidiana e evolução durante tratamento com IFN. MÉTODOS: Avaliação prospectiva de 112 indivíduos com infecção crônica pelo VHC, 30 tratados com IFN, e 183 controles. Realizaram-se avaliações clínica, hormonal e de auto-imunidade tireoidiana e ultra-sonografia de tireóide no início e durante tratamento. Avaliações de globulina transportadora de hormônios tireoidianos (TBG), de CXCL10 e de biópsia hepática foram feitas pré-tratamento. Análises dos polimorfismos do gene CTLA4 -318C>T, A49G e CT60 foram realizadas por PCR-RFLP e de AT(n) por análise de fragmento através de eletroforese capilar. RESULTADOS: A frequência de DAIT entre infectados por VHC não diferiu dos controles (10,7 vs 13,5%, p=0,585). Os limites de distribuição dos níveis de T3 (T3T) e T4 (T4T) totais foram superiores aos de referência (T3T 112-246 ng/dL; T4T 7,8-15,2 g/dL), assim como de TBG (17-47 mg/L). TBG correlacionou-se com T3T (r=0,654, p<0,001) e T4T (r=0,741, p<0,001). Heterogeneidade (p=0,027) e hipoecogenicidade de parênquima (p=0,002) foram mais frequentes nos pacientes com DAIT. Aumento de vascularização esteve presente em 49,2% dos infectados sem distúrbio tireoidiano. CXCL10 esteve aumentada nos infectados (p=0,006), mas não se relacionou com disfunção tireoidiana. Sua elevação correspondeu ao grau de atividade necro-inflamatória na biópsia hepática...

INTRODUCTION: Autoimmune disorders are frequent in patients infected by the hepatitis C virus (HCV). Although the association with autoimmune thyroid diseases (AITD) is controversial, thyroid disturbance could occur or worsen with IFN and ribavirin treatment. The aims of the study were evaluate thyroid function in HCV-infected patients, characterize thyroid disturbance prior and after IFN treatment and analyze the frequency of the genotypes of the polymorphisms of CTLA4 gene, and their relation to clinical and laboratorial features, presence of thyroid dysfunction and disturbance along IFN treatment. METHODS: Prospective evaluation of 112 chronically HCV-infected subjects, 30 treated with IFN, and 183 controls. Clinical, hormonal, thyroid autoimmunity and ultrasound exams were performed before and during treatment. Thyroxine-binding globulin (TBG), CXCL10 and hepatic biopsies were also evaluated before treatment. Analysis of polymorphisms of CTLA4 gene -318C>T, A49G and CT60 were made by PCR-RFLP and AT(n) polymorphism analysis by capillary electrophoresis in automatic sequencer. RESULTS: The frequency of AITD among HCV-infected subjects was similar to the rate among controls (10.7 vs 13.5%, p=0.585). Total T3 (T3T) and T4 (T4T) distributions were right shifted (T3T 112-246 ng/dL; T4T 7.8-15.2 g/dL), as was TBG (17-47 mg/L). TBG correlated to both T3T (r=0.654, p<0.001) and T4T (r=0.741, p<0.001). Thyroid heterogeneity (p=0.027) and hipoechogenicity (p=0.002) were associated with AITD and, most notably, increased vascularization was present in 49.2% of HCV-infected patients without thyroid disturbance. CXCL10 was higher in HCV-infected group (p=0.006) but was not related to thyroid dysfunction. Increase in CXCL10 levels were consistent with hepatic necroinflammatory activity (p=0.006) and correlated to T3T (r=0.388, p=0.003), T4T (r=0.444, p=0.001) and TBG (r=0.551, p<0.001). Nineteen percent of subjects treated with IFN presented autoimmune thyroiditis and...

Tratamento de hemangioma gigante com interferon alfa: relato de dois casos / Treatment of giant hemangioma with interferon-alpha: report of two cases

O objetivo do trabalho é descrever o uso de interferon alfa no tratamento de pacientes com hemangioma gigante. Os autores relatam e analisam dois casos de hemangioma gigante em tratamento com interferon alfa. IBS, 3 anos, em acompanhamento no Ambulatório de Hematologia desde um ano de idade com quadro de lesão angiomatosa em praticamente toda hemiface direita, acompanhada de sangramentos gengivais importantes. Após a realização de exames complementares (Angiorressonância magnética) e feito o diagnóstico de hemangioma gigante em face, foi iniciado tratamento com prednisona e, posteriormente, associação com interferon alfa e observada importante melhora do quadro, resultando na diminuição dos episódios de sangramento e no tamanho do tumor. C.N.P., 12 anos, apresentando nódulo em região lateral de joelho esquerdo há 2 anos, com aumento progressivo do tamanho e dor local. Fez uso de prednisona e, sem melhora do quadro, introduzido interferon alfa com regressão importante do tamanho do tumor. O tratamento com interferon alfa deve ser considerado no tratamento de hemangiomas, pois apresenta bons resultados em relação à diminuição do tamanho do tumor e, conseqüentemente, reduz as intercorrências clínicas associadas à sua presença, principalmente os sangramentos.

The aim of this study is to describe the treatment using interferon-alpha of giant hemangiomas in children. The authors report two cases of children presenting with giant hemangiomas treated using interferon-alpha and analyze the results. IBS, 3 years-old, has been followed up in Famema Hemathology Service since she was 1 year-old with a tumor on the face and persistent bleeding. After clinical and radiologic evaluations and suggested the diagnosis of giant hemangioma, she started treatment with interferon-alpha. A great clinical improvement was observed a reducing of the number of episodes of bleedings and a decrease in of the tumor size. CNP, 12 years-old, came to this service in the last year presenting with a small painful tumor on the left knee. She had already tried a treatment with Prednisone with no improvement. Treatment with interferon-alpha was initiated with a significant decrease in its size. The use of interferon-alpha should be considered in the treatment of giant hemangioma due to its favorable results related to a reduction in the tumor size and the episodes of bleeding.

The Treatment of Liver Hemangioma Associated with Kasabach-Merritt Syndrome in Neonates

Hemangioma is the most frequent liver tumor in infancy. The treatment of hepatic hemangioma includes medical, surgical, and non-operative interventional therapy. There are no standard medical regimens currently considered consistently effective. MDMP (megadose methylprednisolone) and alpha-interferon can be used for medical treatment. Interventional occlusion of feeding arteries in symptomatic hepatic hemangioma is considered a safe and effective alternative to early open surgery. Untreated symptomatic patients with heart failure have a high mortality rate. For this reason symptomatic patients with heart failure may require non-operative treatment such as interventional embolization, because hepatic resection is burdened with high risk. We report our experiences of two patients with neonatal liver hemangiomas whose clinical courses were complicated by cardiac failure to whom medical treatment and/or interventional vascular occlusion were done. Both patients had Kasabach-Merritt syndrome complicated with cardiac failure. Initially, the masses were considered unresectable. In one case, we performed interventional therapy in addition to medical treatment. In another case, we tried medical therapy with megadose steroid and alpha-interferon. Unfortunately, in spite of the treatments, the patients died of severe hemorrhage.

Relationship Between Core Gene Mutations of Hepatitis B Virus and Response to Alpha Interferon Therapy in Chronic Hepatitis B / 대한간학회지

BACKGROUND/AIMS: Treatment of chronic hepatitis B with interferon results in a sustained loss of hepatitis B virus DNA and hepatitis B e antigen (HBeAg) and remission of liver disease only in a proportion of cases. Recently, mutations of hepatitis B virus (HBV) core gene have been reported as being related to the failure of interferon treatment in chronic hepatitis B. This study investigated whether core gene mutations of HBV are related to non-response to interferon therapy and whether the recurrence of HBeAg and HBV DNA in initial responders to interferon therapy is associated with the emergence of HBV core gene mutants. METHODS: The precore/core gene sequence was determined by polymerase chain reaction (PCR) and direct sequencing of PCR product in serum samples obtained before interferon treatment from 10 responders and 10 non-responders to interferon therapy. In addition, precore/core gene sequence was determined in serum samples obtained before interferon treatment and after recurrence from 10 patients who showed recurrence of HBeAg and HBV DNA after initial response to interferon therapy. RESULTS: In samples from 10 responders, there were 7 missense mutations and 71 silent mutations. However, there were 43 missense mutations and 109 silent mutations in samples from 10 non-responders. In samples obtained before interferon treatment from the 10 patients who showed recurrence after initial response, 8 missense mutations and 74 silents mutations were found. The nucleotide sequences from the samples obtained after the recurrence showed 6 silent nucleotide substitutions compared with the sequences from the samples obtained before interferon treatment. CONCLUSIONS: Mutations in the core protein of HBV occur more frequently in non-responders than responders to interferon therapy of chronic hepatitis B and may be a factor responsible for the failure of interferon treatment. The recurrence of HBeAg and HBV-DNA in initial responders to interferon therapy is not associated with the emergence of the HBV core gene mutants.

Recombinant Alfa-interferon Therapy in HBGN with HBe Antigenemia / 대한신장학회잡지

Recently the results of alpha-interferon treatement in hepatitis B virus associated glomerulonephritis showed a reduction of proteinuria and a loss of HBeAg in some treated patients. But, alpha- interferon therapy was mainly tried in membranous nephropathy of children. So, we treated 13 adults patients with recombinant alpha-interferon who were diagnosed as HBV associated membranous nephropathy(2) and membranoproliferative GN(11) at Seoul National unversity hospital. All of them had nephrotic range proteinuria and HBe antigenemia for more than 6 months, normal serum creatinine level and had no other systemic disease. Three million units of recombinant alpha-interferon was given six times a week for 16 weeks intramuscularly and the therapeutic effect was analyzed during treatment periods, especially in terms of changes in urine protein excretion and serum HBeAg. And we compared them with 14 control patients who had received conservative therapy only. As a results, at the end of interferon therapy, serum HBeAg disappeared in 4 of 13 treated patients, and serum HBsAg disappeared in 1 of 4. At the end of therapy, proteinuria diminished to non-nephrotuc range in 6 of 13 treated patients and decrement of proteinuria was accompanied with disappearance of serum HBeAg in 3 patients. And proteinuria diminished in 5 of 11 MPGN patients and serum HBeAg disappread in 3 of them. But in 14 controls there were no significant changes in 24 hour urine protein excretion and serum HBeAg. During interferon therapy, mild febrile reaction was developed in 8 patients, anemia in 3 patients, and cytopenia in 7 patients, but most of these adverse effects resolved spontaneously after discontinuation of interferon therapy. During follow up periods over 1 years, proteinuria relapsed to nephrotic range in 3 of 6 patients and serum HBeAg reappreared in 2 of them. In conclusion, the alpha-interferon at the dose induced a clearance of HBeAg and the decrement of the proteinuria in some adult MN and MPGN patients. And these results suggested the possibilities that HBeAg might be involved in the pathogenesis of HBV associated MPGN and alpha-interferon might be effective in some HBV associated MPGN.

A Case of Hypothyroidism Induced by Alpha-Interferon Therapy for Chronic Hepatitis B / 대한간학회지

Thyroid dysfunction has heen reported as a side effect of alpha-interferon(IFN) therapy. The incidence of thyroid disorders was 1.2-12%' duripg 1FN therapy for chronic active hepatitis. We experienced a case of hypothyroidism developed after IFN therapy in a 48 year-old man with chronic hepatitis B. Baseline thyroid function before IFN therapy was normal and thyroid auioantibodies were also negative. High tiers ol' antimicrosomal antibody and anti-thyroglobulin antibody appeared and severe hypothyroidism followed at 6 months after starting the IFN therapy.

The Effects of Recombinant Human alpha-Interferon on Epidemic keratoconjunctivitis

We investigated the clinical effects and drug toxicities of high concentrated recombinant human alpha-interferon eyedrops in acute epidemic keratoconjunctivitis(ARK). We examined the side effects of alpha-interferon eyedrops after instillation to the 34 general healthy patients, and compared the clinical effects after randomized blind administration of the different concentration eyedrops or placebo in 117 AEK. No significant ocular complications in the 34 general healthy patients was observed. In AEK, improvement of symptoms and signs were observed at the mean 3.2 days of 10.000 IU/ml group, 3.1 days of 100,000 IU/ml group, and 3.2 days of 500,000 IU/ml group after instillation of alpha-interferon. comparing 4.4 days of placebo(P<0.01). We have also observed early absorption of conjunctival pseudomembrane, and the decreased incidence of keratitis. We suggest that the topical application of alpha-interferon might be clinically useful to help early recovery and decrease the incidence of ocular complications of AEK.

The effects of prolonged treatment in children with chronic hepatitis B with combination of alpha-interferon and acyclovir

This study was conducted to evaluate the effect of prolonged treatment in children with chronic hepatitis B with combination of alpha-interferon and acyclovir. The study population consisted of 7 patients with chronic hepatitis B who showed histological findings compatible with chronic active hepatitis (4 cases) or chronic persistent hepatitis (3 cases) on liver biopsy and had elevated AST and ALT with positive HBsAg, HBeAg and HBV-DNA for more than 6 months. Recombinant interferon-alpha-2 was given in a dose of 3 million IU/m2 daily for 3 months with acyclovir in a dose of 15mg/Kg of body weight every 12 hours for 7 days of each month for 3 months. Then, the same dose of interferon was given thrice a week for 9 more months. One patient who had vertically transmitted hepatitis B from her mother had received only 6 months of treatment in total as she did not show any effect after 6 months of treatment. Among 6 patients who had positive HBV-DNA on entry to the study, 4 patients (66.7%) showed conversion of HBV-DNA to negative. HBeAg was converted to negative in 3 patients (42.9%). AST and ALT became normal in 6 cases but HBsAg remained positive in all cases. prolonged treatment in children with chronic hepatitis B with combination of alpha interferon and acyclovir seems to be beneficial but the proper dosage and duration of therapy need to be determined with further and controlled study.

Effect of alpha-interferon treatment on serum ALT levels in patients with chronic hepatitis C / 영남의대학술지

The prognosis of chronic hepatitis C is very variable. In some, the disease is progressive and cirrhosis can develop from chronic hepatitis C. Hepatitis C virus (HCV) may act as a trigger towards hepatocellular carcinoma in patients with cirrhosis. Interferon has been used for the treatment of chronic hepatitis C in abroad. 16 patients with chronic C liver disease were treated with alpha-interferon (alfa-2b : "Intron A" Schering Corp. Kenilworth, NJ). All patients were given alpha-interferon in subcutaneous doses of 3 million units three times weekly for 1 to 9 months. During therapy, CBC and ALT levels were checked weakly to monthly. After therapy,. patients were followed for 1 to 8 months. Among 16 patients treated with alpha-interferon, progressive decrease of ALT levels was observed in 14 (87.5%). In 11 patients (68.8%), ALT levels fell into the normal range during therapy, and in 9 of 11, within one month after therapy. 6 months after the completion of therapy in 4 of 9 patients (44.4%) whose ALT levels were in the normal range. alpha-interferon seems to have effect in controlling disease activity in patients with chronic hepatitis C. But the changes in the usage of alpha-interferon, dose and duration, long term follow up and more convenient and simple tests for HCV detection are recommended for the better effect and the exact evaluation on the effect of alpha-interferon therapy in patients with chronic hepatitis C.

The Effects of Recombinant Human Alpha-lnterferon on Epidemic Keratoconjunctivitis

The one hundred ninty three patients of epidemic keratoconjunctivitis (EKC) were treated with recombinant human alpha interferon (Re-Hu-INF-a eyedrop, 30,000IU/Vial, Cheil Foods and Chemicals Inc.) at kangnam St. Mary's Hospital, Catholic University Medical College, Chungang University Hospital, Kangdong Sacred Heart Hospital, Hallym University and Kims's Eye Clinic and the following results were obtained after at least 21 days follow-up. 1. The total patients of EKC were 266; 193 of patients were treated with INF and another 73 patients were treated with antibiotic eye drop only as a control group. The age ranged from 3 to 79 year-old and the average age were 29.6 in interferon group and 36.3 in control group. 2. There was no significant difference between two groups in number of eyes involved. The frequencey of infection route was family, swimming pool, and eye clinic order. Adenovirus was the most common causative agent according to the cytopathic effect of HeLa cell inoculation. 3. In most of cases, there was little symptomatic manifestation, if ever, malaise was the most common systemic symptom in both groups. 4. The symptomatic improvement after INF treatment Was began at 3.8 days in INF group comparing to 10.8 days in control group. In INF treated group, the subjective symptom was disappeared in 70.5% of patients within 4 days. But in control gorup, disappearance of subjective symptom was noted in only 17.8% of patients and the results were statistically significant. 5. The eariler INF treatment, the better improvement of EKC and the sign improved first was foreign body sensation. 6. There was little side effect of INF treatment, but ocular pain was occurred in 8% From these results, we suggest that recombinant human alpha interferon eyedrop in EKC treatment is effective and the earlier application is more effective especially.