LIVER TRANSPLANTATION FOR BILE DUCT INJURY AFTER CHOLECYSTECTOMY.

BACKGROUND: Bile duct injury is a life-threatening complication that requires proper management to prevent the onset of negative outcomes. Patients may experience repeated episodes of cholangitis, secondary biliary cirrhosis, end-stage liver disease and death. OBJECTIVE: To report a single center experience in iatrogenic secondary liver transplantation after cholecystectomy and review the literature. METHODS: This was a retrospective single center study. Of the 1662 liver transplantation realized, 10 (0.60 %) were secondary to iatrogenic bile ducts injuries due cholecystectomies. Medical records of these patients were reviewed in this study. RESULTS: Nine of 10 patients were women; the median time in waiting list and between cholecystectomy and inclusion in waiting list was of 222 days and of 139.9 months, respectively. Cholecystectomy was performed by open approach in eight (80%) cases and by laparoscopic approach in two (20%) cases. The patients underwent an average of 3.5 surgeries and procedures before liver transplantation. Biliary reconstruction was realized with a Roux-en-Y hepaticojejunostomy in nine (90%) cases. Mean operative time was 447.2 minutes and the median red blood cell transfusion was 3.4 units per patient. Mortality in the first month was of 30%. CONCLUSION: Although the liver transplantation is an extreme treatment for an initially benign disease, it has its well-defined indications in treatment of bile duct injuries after cholecystectomy, either in acute or chronic scenario.

Transplante de fígado para tratamento de lesão de via biliar após colecistectomia / Liver transplantation for bile duct injury after cholecystectomy

ABSTRACT BACKGROUND: Bile duct injury is a life-threatening complication that requires proper management to prevent the onset of negative outcomes. Patients may experience repeated episodes of cholangitis, secondary biliary cirrhosis, end-stage liver disease and death. OBJECTIVE: To report a single center experience in iatrogenic secondary liver transplantation after cholecystectomy and review the literature. METHODS: This was a retrospective single center study. Of the 1662 liver transplantation realized, 10 (0.60 %) were secondary to iatrogenic bile ducts injuries due cholecystectomies. Medical records of these patients were reviewed in this study. RESULTS: Nine of 10 patients were women; the median time in waiting list and between cholecystectomy and inclusion in waiting list was of 222 days and of 139.9 months, respectively. Cholecystectomy was performed by open approach in eight (80%) cases and by laparoscopic approach in two (20%) cases. The patients underwent an average of 3.5 surgeries and procedures before liver transplantation. Biliary reconstruction was realized with a Roux-en-Y hepaticojejunostomy in nine (90%) cases. Mean operative time was 447.2 minutes and the median red blood cell transfusion was 3.4 units per patient. Mortality in the first month was of 30%. CONCLUSION: Although the liver transplantation is an extreme treatment for an initially benign disease, it has its well-defined indications in treatment of bile duct injuries after cholecystectomy, either in acute or chronic scenario.

RESUMO CONTEXTO: A lesão da via biliar é uma complicação que pode ameaçar a vida e que requer manejo adequado para prevenir o aparecimento de desfechos negativos. Os pacientes podem apresentar episódios repetidos de colangite, cirrose biliar secundária, doença hepática terminal e até mesmo morte. OBJETIVO: Avaliar a experiência de um único centro em transplante hepático secundário a lesão iatrogênica de via biliar pós-colecistectomia e fazer uma revisão de literatura. MÉTODOS: Este foi um estudo retrospectivo de um único centro. Dos 1662 transplantes de fígado, 10 (0,60%) foram secundários a lesões iatrogênicas das vias biliares devido à colecistectomias. Os prontuários médicos desses pacientes foram revisados neste estudo. RESULTADOS: Nove dos dez pacientes eram mulheres; o tempo médio em lista de espera de transplante e entre colecistectomia e inclusão na lista de espera foi de 222 dias e de 139,9 meses, respectivamente. A colecistectomia foi realizada por abordagem aberta em oito (80%) casos e por abordagem laparoscópica em dois (20%) casos. Os pacientes foram submetidos a uma média de 3,5 cirurgias e procedimentos antes do transplante de fígado e a reconstrução biliar foi realizada com hepaticojejunostomia em Y-de-Roux em nove (90%) casos. O tempo operatório médio foi de 447,2 minutos e a média de transfusão de concentrados de hemácias foi de 3,4 unidades por paciente. Mortalidade no primeiro mês foi de 30%. CONCLUSÃO: Embora o transplante de fígado seja um tratamento extremo para uma doença inicialmente benigna, ele tem suas indicações bem definidas no tratamento de lesões biliares após colecistectomia, seja em um cenário agudo ou crônico.

[Acute abdomen as initial manifestation of metastatic melanoma]. / Abdome agudo como manifestação inicial de melanoma metastático: relato de caso.

The malignant melanoma is a relatively common neoplasia, with origin generally in the melanocytics cells in the skin, but with presentation of other possible primary lesions, being presented in this, a case witnessed of liver and mesentery metastases with unknown primary sites.

Abdome agudo como manifestação inicial de melanoma metastático: relato de caso / Acute abdomen as initial manifestation of metastatic melanoma

The malignant melanoma is a relatively common neoplasia, with origin generally in the melanocytics cells in the skin, but with presentation of other possible primary lesions, being presented in this, a case witnessed of liver and mesentery metastases with unknown primary sites.

Epstein-Barr virus-associated gastric carcinoma in Brazil: comparison between in situ hybridization and polymerase chain reaction detection

Epstein-Barr virus (EBV) has been associated with 10% of gastric carcinomas. The aim of this study was to determine the frequency of EBV in gastric carcinomas in Brazil assessed by in situ hybridization (ISH) and PCR, which would contribute to the characterization of the clinical and pathological aspects of EBV-associated gastric carcinomas. One hundred and ninety-two gastric carcinoma cases were collected at hospitals in two Brazilian states. Seventy-three out of 151 cases were PCR(+), while 11/160 cases were ISH(+). Nine out of eleven ISH(+) cases displayed a diffuse staining pattern and 2 out of 11 a focal pattern. Both techniques showed that the EBV(+) cases were characterized by their association with males, older patients, lower gastric region, intestinal type, advanced stage and poorly to moderately differentiated tumors. The concordance between the two techniques was 55.8% (Cohen's kappa index = 0.034). Four cases were ISH(+)/PCR(-), while 49 cases were PCR(+)/ISH(-). Only two cases showed stained lymphocytes by ISH and one of them was PCR(-). The observed discrepancy between the two techniques could not be explained just by the elevated accuracy of PCR. ISH(+)/PCR(-) carcinomas may be encountered if EBV is not present in the whole tumor tissue or if there are polymorphisms in the sequences of the viral genome amplified. On the other hand, the high frequency of PCR(+) results associated with the absence of ISH staining in lymphocytes and/or tumors cells suggests that the virus may be present in tumor cells or other cell types without expressing EBER1, the target of the ISH technique.

Epstein-Barr virus-associated gastric carcinoma in Brazil: comparison between in situ hybridization and polymerase chain reaction detection.

Epstein-Barr virus (EBV) has been associated with 10% of gastric carcinomas. The aim of this study was to determine the frequency of EBV in gastric carcinomas in Brazil assessed by in situ hybridization (ISH) and PCR, which would contribute to the characterization of the clinical and pathological aspects of EBV-associated gastric carcinomas. One hundred and ninety-two gastric carcinoma cases were collected at hospitals in two Brazilian states. Seventy-three out of 151 cases were PCR(+), while 11/160 cases were ISH(+). Nine out of eleven ISH(+) cases displayed a diffuse staining pattern and 2 out of 11 a focal pattern. Both techniques showed that the EBV(+) cases were characterized by their association with males, older patients, lower gastric region, intestinal type, advanced stage and poorly to moderately differentiated tumors. The concordance between the two techniques was 55.8% (Cohen's kappa index = 0.034). Four cases were ISH(+)/PCR(-), while 49 cases were PCR(+)/ISH(-). Only two cases showed stained lymphocytes by ISH and one of them was PCR(-). The observed discrepancy between the two techniques could not be explained just by the elevated accuracy of PCR. ISH(+)/PCR(-) carcinomas may be encountered if EBV is not present in the whole tumor tissue or if there are polymorphisms in the sequences of the viral genome amplified. On the other hand, the high frequency of PCR(+) results associated with the absence of ISH staining in lymphocytes and/or tumors cells suggests that the virus may be present in tumor cells or other cell types without expressing EBER1, the target of the ISH technique.

Differential expression of MYC in H. pylori-related intestinal and diffuse gastric tumors.

Evidence suggests that the carcinogenic process guided by Helicobacter pylori is related to the expression of cell cycle and apoptosis proteins as BCL-2, BAX, and MYC. However, the literature is conflicting regarding the expression frequency in the histological subtypes and did not consider cagA gene presence. To investigate the expression of these proteins considering the histological subtypes of gastric cancer associated with H. pylori (cagA), a total of 89 cases were used. H. pylori infection and cagA status were determined by PCR. Immunodetection was performed for MYC, BCL-2, and BAX proteins. H. pylori was found in 95.5% of the patients, among them, 65.8% were cagA(+). Nuclear MYC was detected in 36.4%, BAX in 55.7%, while BCl-2 in just 5%. Nuclear MYC staining was significantly lower in the intestinal than diffuse subtype (p = 0.008) and was related with the presence of H. pylori cagA(+). Additionally, most of the few cases cytoplasmic MYC positive were in the intestinal subtype. In diffuse tumors, although most nuclear MYC positive cases were cagA(+), it was not significant. No difference was observed between BCL-2 or BAX expression considering the presence of cagA gene in the histological subtypes. It seems that MYC could be relevant for the diffuse tumorigenic pathway associated with H. pylori and possibly influenced by the presence of cagA gene, while in intestinal tumors, the tumorigenic pathway does not occur through the MYC expression.

Detecção do vírus Epstein-Barr (EBV) em adenocarcinomas gástricos procedentes dos estados do Ceará e de São Paulo / Epstein-Barr virus (EBV) detection in gastric carcinomas from Ceará and São Paulo states, in Brazil

INTRODUÇÃO: O vírus Epstein-Barr (EBV) está associado a cerca de 10 por cento dos adenocarcinomas gástricos, representando mais de 50 mil casos por ano no mundo. Apesar dos estudos realizados em várias partes do mundo, alguns aspectos clinicopatológicos permanecem controversos. OBJETIVOS: O presente estudo teve como objetivo analisar as características clinicopatológicas de casos de adenocarcinomas gástricos procedentes dos estados de São Paulo e Ceará, correlacionando-os com a detecção de EBV. MATERIAIS E MÉTODOS: Foram obtidos 192 casos de adenocarcinomas gástricos de hospitais dos estados de São Paulo e do Ceará, dos quais 160 foram submetidos à técnica de RNA-hibridização in situ para detecção de EBV. RESULTADOS: Dos 160 casos, 11 (6,9 por cento) foram EBV-positivo, exibindo intensa marcação nuclear em células tumorais. Destes, dois casos também apresentaram linfócitos infiltrados marcados. Não encontramos marcação em tecido normal ou pré-neoplásico. São Paulo e Ceará apresentaram as frequências 3/60 (5 por cento) e 8/100 (8 por cento), respectivamente, e maior relação do EBV com indivíduos do sexo masculino, de idade avançada, com tumores do tipo intestinal, de estadiamento elevado e grau pouco a moderadamente diferenciado. Os casos do Ceará exibiram aumento relativo de tumores EBV(+) localizados na cárdia, enquanto os casos de São Paulo demonstraram aumento naqueles localizados no corpo gástrico. CONCLUSÃO: A frequência de tumores EBV(+) do presente estudo situa-se nos valores descritos na literatura mundial. Entre os achados, um deles não encontra paralelo na literatura mundial e refere-se ao elevado percentual de tumores EBV(+) no corpo gástrico observado nos casos de São Paulo.

INTRODUCTION: The Epstein-Barr virus (EBV) has been associated with approximately 10 percent of gastric adenocarcinomas, which represents more than 50,000 cases/year worldwide. Despite the studies undertaken in several countries, some clinical-pathological aspects remain contentious. OBJECTIVE: The objective of this study was to analyze clinical-pathological features of gastric adenocarcinomas from two Brazilian states, São Paulo and Ceará, by correlating them with EBV detection. MATERIALS AND METHODS: One hundred ninety-two gastric adenocarcinoma cases were selected from hospitals in São Paulo and Ceará, of which 160 were submitted to RNA in situ hybridization for EBV detection. RESULTS: Eleven (6.9 percent) out of 160 cases were EBV-positive with intense nuclear staining in tumor cells. Among these, two cases also showed stained infiltrating lymphocytes. There was no staining in normal or preneoplastic tissue. São Paulo and Ceará yielded the respective results: 3/60 (5 percent) and 8/100 (8 percent). In both states, EBV was more prevalent among elder male patients with little to moderately differentiated intestinal tumors in advanced stage. Ceará cases substantiated a relative increase in EBV(+) tumors located in the cardia, whereas São Paulo cases presented an increase in the gastric corpus. CONCLUSION: The frequency of EBV(+) tumors is similarly described in the literature. Among our findings, the elevated percentage of EBV(+) tumors in the gastric corpus, which was observed in São Paulo cases, is unprecedented in the literature.

p27KIP1 expression in gastric cancer: differential pathways in the histological subtypes associated with Helicobacter pylori infection.

OBJECTIVE: Decreases in p27(KIP1) and C-MYC expression have been associated with Helicobacter pylori infection. Furthermore, C-MYC seems to be a transcriptional repressor of p27(KIP1). Therefore, in a series of gastric adenocarcinomas we studied the association of p27(KIP1) expression with H. pylori genotype (vacA, cagA, cagE and virB11) and the involvement of C-MYC in this process. MATERIAL AND METHODS: Expression of p27(KIP1) and C-MYC was determined by immunohistochemistry in 84 gastric adenocarcinoma samples and H. pylori infection and genotype were determined by polymerase chain reaction. RESULTS: Most p27(KIP1)-negative cases (94.0%) were H. pylori-positive and 44.8% were C-MYC-positive. In the diffuse gastric cancer subtype, p27-negative-C-MYC-positive was the most frequent combination (cluster II), and was associated with the more pathogenic H. pylori strains. Although an association with p27(KIP1) and H. pylori strain was found in the intestinal gastric cancer subtype, negativity for p27(KIP1) and C-MYC markers was the most frequent cluster, followed by cluster II, and both were present, independent of the H. pylori genotype. CONCLUSIONS: Reduced expression of p27(KIP1) was closely linked to H. pylori infection, and was dependent on the more pathogenic strains. Moreover, intestinal and diffuse subtypes showed distinct carcinogenic pathways influenced by H. pylori strains. These data add insight to the differential influence and relevance of H. pylori genotype in gastric cancer development.

The relationship between Helicobacter pylori genes cagE and virB11 and gastric cancer.

BACKGROUND: The association between Helicobacter pylori gene diversity and gastric cancer has been poorly reported, although it is one of the important ways to explain the gastric pathogenesis. The aim of this study was to investigate the frequency of cagE and virB11 genes in H. pylori isolated from patients with gastric cancer and to analyze the histology profiles. MATERIALS AND METHODS: The presence of H. pylori and subtypes (cagE and virB11) was detected by PCR from the genomic DNA of 101 patients who had been diagnosed with gastric cancer. The cases were grouped according to the presence/absence of the genes studied and were analyzed in relation to histopathological parameters. RESULTS: H. pylori infection was detected in 94 out of 101 (93.1%) gastric carcinomas. The cases were categorized into the following groups: cagE+/virB11+, cagE+/virB11-, cagE-/virB11+, and cagE-/virB11-. Frequencies were: 50% (47/94) cagE+/virB11+, 3.2% (3/94) cagE+/virB11-, 10.6% (10/94) cagE-/virB11+, and 36.2% (34/94) cagE-/virB11-. Tumors in the gastric antrum were predominant. An exception was the cagE-/virB11- group, in which tumors had a tendency to be located in the gastric cardia; the majority of the cardia tumors (56% (14/25)) were in this group. Intestinal histology type was the most frequent, but the cagE+/virB11- group only had diffuse tumors. H. pyloricagE+/virB11+ occurred most frequently (except at stage III), and was present at all gastric cancer stages. CONCLUSIONS: This study is the first to include a relevant number of gastric cancer cases with H. pylori infection, reporting the frequency and relationship of cagE and virB11 genes and the genesis of this tumor. The presence of these cag pathogenicity island genes shows that they are important factors for the pathogenesis and malignancy of gastric cancer related to H. pylori.

Helicobacter pylori and EBV in gastric carcinomas: methylation status and microsatellite instability.

AIM: To verify the methylation status of CDH1, DAPK, COX2, hMLH1 and CDKN2A genes and to evaluate their association with Helicobacter pylori (H. pylori)-cagA(+) and Epstein Barr virus (EBV) infections in gastric adenocarcinomas. METHODS: Methylation-specific PCR (MSP) assay was performed in 89 primary gastric carcinomas (intestinal and diffuse types). Microsatellite instability (MSI) analysis was performed using the BAT26 primer set and PCR products were analyzed with the ABI PRISM 3100 Genetic Analyzer using Genescan 3.7 software (Applied Biosystems). Detection of H. pylori and genotyping were performed by PCR, using specific primers for ureaseC and cagA genes. The presence of EBV was assessed by in situ hybridization. Statistical analyses were performed using the chi(2) or Fisher's exact test. RESULTS: The most frequent hypermethylated gene was COX-2 (63.5%) followed by DAPK (55.7%), CDH1 (51%), CDKN2A (36%) and hMLH1 (30.3%). Intestinal and diffuse adenocarcinomas showed different methylation profiles and there was an association between methylation of E-CDH1 and H. pylori-cagA(+) in the intestinal adenocarcinoma type. MSI was correlated with hMLH1 methylation. There was an inverse correlation between DAPK hypermethylation and MSI. CONCLUSION: We found a strong association between CDH1 methylation and H. pylori-cagA(+) in intestinal-type gastric cancer, association of MSI and better prognosis and an heterogeneous COX-2 overexpression.

Tricobezoar retal: relato de um caso raro na literatura / Rectal trichobezoar: report of a rare case in literature

O bezoar compreende o acúmulo de substâncias não-digeríveis (folhas, pêlos, pedras, produtos lácteos, medicamentos, entre outros) no trato digestório. Sua importância deve-se ao quadro clínico por vezes inespecífico e às complicações que podem surgir. Apresentamos aqui o caso de uma paciente de 62 anos atendida no serviço de Cirurgia Oncológica com quadro de um mês de evolução e suspeita inicial de neoplasia colorretal. Exames complementares não elucidaram o diagnóstico, que só foi feito após abordagem cirúrgica por laparotomia exploratória. Após a mesma, a paciente evoluiu com piora do estado geral e foi transferida para a UTI do hospital, falecendo devido a complicações septicêmicas. Esse caso demonstra as dificuldades para se chegar nesse diagnóstico e que o atraso pode resultar em complicações letais para o paciente.

Bezoar is a foreign body in the digestive tract originated from ingestion of non-digestible substances (leaves, hair, rocks, milk products, drugs, etc). Undetermined clinical signs and severe complications make it an important diagnosis. We report the case of a 62-year-old female patient who was seen at the oncological surgery department of Santa Casa de Misericórdia de Fortaleza. The patient reported having low gastrointestinal symptoms for a month. Colorectal neoplasia was initially suspected. Blood and image diagnostic tests were not elucidative. The diagnosis was just confirmed after surgical approach. The patient had a poor postoperative follow-up and died after complications of septicemia. This case demonstrates the difficulties to confirm such diagnosis and the lethal complications caused by diagnosis delay.

H pylori (CagA) and Epstein-Barr virus infection in gastric carcinomas: correlation with p53 mutation and c-Myc, Bcl-2 and Bax expression.

AIM: To investigate the interrelationship between H pylori and Epstein-Barr virus (EBV) infection in the gastric carcinogenesis having in focus the p53 mutation and the c-Myc, Bcl-2 and Bax expression. METHODS: seventy-one gastric carcinoma tissues were assessed by polymerase chain reaction (PCR) for H pylori and in situ hybridization for EBV. c-Myc, Bcl-2 and Bax expression were detected by immunohistochemistry and single-stranded conformational polymorphism (SSCP) for p53 mutation. RESULTS: The positivity rates for H pylori and EBV were 94.4% and 8.45%, respectively. The majority of the cases displayed only the H pylori presence. All EBV positive cases were also H pylori positive. None infectious agent was observed in 5.55% of the cases. The intestinal type tumor was more frequent in the co-infected and non-infected groups. The female predominated in the non-infected group showing statistical significance (70.4% vs 29.6%, P = 0.039). The Bcl-2 was only detected in the group exclusively infected by H pylori. However, c-Myc and Bax were detected in the three groups but with a low frequency in the co-infected group. Mutation of p53 was present in all groups, with the highest frequencies in the H pylori positive groups. CONCLUSION: The frequency of H pylori infection in gastric carcinomas was high. The presented data indicated that gastric carcinogenesis has different pathways depending of the presence of the two investigated infectious agents, suggesting a possible involvement of H pylori with apoptotic process. The low expression of c-Myc and Bax in the EBV-positive groups suggests that EBV may inhibit the expression of these proteins. Nevertheless, p53 mutation shows to be a relevant alteration, independent of both infectious agents.