Controversias en cirugía: Erradicación del Helicobacter pylori ¿Terapia a todos o según indicaciones usuales? / Controversies in surgery: Eradication of Helicobacter pylori. Therapy for all or according to usual indications?

La infección por Helicobacter pylori (H. pylori), es la infección bacteriana crónica más frecuente de la raza humana, afecta al 50 % de la población mundial y, por lo menos, al 80 % de la población colombiana. Esta bacteria es re-conocida desde hace más de 15 años como un carcinógeno tipo I. De acuerdo con las indicaciones del Consenso de "Maastricht V" esta infección debe ser buscada y tratada en los pacientes con úlcera péptica activa, linfoma MALT (por sus siglas en inglés, mucosa associated lymphoid tissue), cáncer gástrico temprano, púrpura que presenten síntomas dispépticos crónicos y usuarios crónicos de AINES. Debido al papel que tiene en la fisiopatología del cáncer gástrico, nace la iniciativa de realizar una búsqueda activa del H. pylori y erradicarlo en todas las personas, incluyendo aquellas asintomáticas en países con alta incidencia de esta neoplasia. Existen diversas publicaciones alrededor del mundo que así lo sugieren, mostrando resultados con impacto positivo en el curso y progresión de la enfermedad, sobre todo en las etapas más tempranas de la infección. Sin embargo, otros autores resaltan la creciente problemática de la resistencia bacteriana, y demuestran que el peso estadístico y los diferentes análisis de los estudios disponibles en la actualidad tienen poca validez para dar una recomendación extendida al paciente asintomático. Se cuestiona que tal vez, estamos utilizando las estrategias inadecuadas para manejar una situación de salud pública, ya que estamos enfocados en impactar a cada individuo con terapias antibióticas complejas, en vez de a la población en general con políticas de salud pública

Helicobacter pylori (H. pylori) infection is the most frequent chronic bacterial infection in humans, affecting 50% of the world population, and at least 80% of the Colombian population. This bacteria has been recognized for more than 15 years as a type I carcinogen. According to the indications of the "Maastricht V" consensus, this infection should be sought and treated in patients with: active peptic ulcer, MALT lymphoma (for its acronym Mucosa associated lymphoid tissue), early gastric cancer, purpura who present with chronic dyspeptic symptoms and chronic users of NSAIDs. Due to the role it plays in the pathophysiology of gastric cancer, the initiative was born to carry out an active search for H. pylori and eradicate it in all people, including those asymptomatic in countries with a high incidence of this neoplasia.There are various publications around the world that suggest the effectiveness of this treatment and the positive impact on the course and progression of the disease, especially in the earliest stages of the infection, since the more advanced stages have less encouraging results regarding progression to malignancy. However, other authors highlight the growing problem of bacterial resistance that we are currently facing and demonstrate that the sta-tistical weight and the different analyzes of the currently available studies have little validity to give an extended recommendation to the asymptomatic patient. It is suggested that perhaps inappropriate strategies to manage this public health situation are being used, since we are focused on impacting each individual with complex antibiotic therapies, instead of the general population with public health policies

USP2a positively regulates TCR-induced NF-κB activation by bridging MALT1-TRAF6

The paracaspase MALT1 is essential for the activation of NF-κB in response to T cell receptor (TCR) stimulation. It recruits downstream TRAF6 and activates the E3 ligase activity of TRAF6 to polyubiquitinate several targets, which ultimately leads to NF-κB activation. Here we identified ubiquitin-specific protease 2a (USP2a) as a MALT1-associated protein by biochemical affinity purification. Endogenous USP2a constitutively interacted with TRAF6, but dynamically interacted with MALT1 and CARMA1 in a stimulation-dependent manner. RNA interference (RNAi)-mediated silencing of USP2a attenuated TCR-induced NF-κB activation and production of interleukin-2 (IL-2). In addition, the ubiquitination of MALT1 and TRAF6 were both suppressed by USP2a knockdown. By knockdown and reconstitution assays, we found that USP2a mediated the interaction between MALT1 and TRAF6 in a catalytic activity-dependent manner. Furthermore, USP2a deSUMOylated TRAF6. Our findings implicate that USP2a plays an important role in TCR signaling by deSUMOylating TRAF6 and mediating TRAF6-MALT1 interaction.

Study on genetic aberrations of ocular mucosa-associated lymphoid tissue lymphomas occurring in southern China / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the genetic aberrations of ocular extranodal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT) type occurring in patients from southern China.</p><p><b>METHODS</b>Fifty seven paraffin-embedded ocular MALT lymphoma specimens from patients in southern China were studied by interphase fluorescence-in-situ hybridization (FISH) for genetic aberrations including t(11;18)(q21;q21)/API2-MALT1, t(1;14)(p22;q32)/IgH-bcl-10, t(14;18) (q32;q21)/IgH-MALT1 and bcl-6/FOXP1 gene translocations.</p><p><b>RESULTS</b>Amongst the 57 cases studied, 9 cases (15.8%) showed chromosome translocations, including 4 cases (7.0%) of t(11;18)(q21;q21)/API2-MALT1, 1 case (1.8%) of t(14;18) (q32;q21)/IgH-MALT1, 1 case (1.8%) of bcl-6 gene-related chromosome translocation and 3 cases (5.3%) of IgH-unknown translocation partner. FISH revealed 17 cases (29.8%) with 3 copies of bcl-6 gene, 21 cases (36.8%) with 3 copies of MALT1 gene and 12 cases (21.1%) with 3 copies of both genes.</p><p><b>CONCLUSIONS</b>The MALT lymphoma-associated chromosome translocations t(11;18)(q21;q21)/API2-MALT1 and t(14;18) (q32;q21)/IgH-MALT1 are demonstrated in ocular MALT lymphomas of southern Chinese patients. The prevalence is significantly different from that reported in northern Chinese and northern American patients, indicating a geographic heterogeneity in the MALT lymphoma-associated genetic aberrations. The presence of 3 copies of bcl-6 and MALT1 genes is the commonest genetic abnormalities observed in ocular MALT lymphomas, suggesting a possible role in MALT lymphomagenesis.</p>

CXCL12/SDF-1 alpha activates NF-kappaB and promotes oral cancer invasion through the Carma3/Bcl10/Malt1 complex / 国际口腔科学杂志·英文版

<p><b>AIM</b>To determine how SDF-1 alpha/CXCR4 activates nuclear factor-kappa B (NF-kappaB) and promotes oral squamous cell carcinoma (OSCC) invasion.</p><p><b>METHODOLOGY</b>A lentivirus-based knockdown approach was utilized to deplete gene expression. NF-kappaB activation was evaluated by Western blot analysis and electrophoretic mobility shift (EMSA).</p><p><b>RESULTS</b>We show that the activation of NF-kappaB by CXCR4 occurs through the Carma3/Bcl10/Malt1 (CBM) complex in OSCC. We found that loss of components of the CBM complex in HNSCC can inhibit SDF-1 alpha induced phosphorylation and degradation of IkappaBalpha, while TNF alpha induced IKK activation remains unchanged. Further, we identified a role for novel and atypical, but not classical, PKCs in activating IKK through CXCR4. Importantly, inhibition of the CBM complex leads to a significant decrease in SDF-1 alpha mediated invasion of OSCC.</p><p><b>CONCLUSION</b>The CBM complex plays a critical role in CXCR4-induced NF-kappaB activation in OSCC. Targeting molecular components of the NF-kappaB signaling pathway may provide an important therapeutic opportunity in controlling the progression and metastasis of OSCC mediated by SDF-1 alpha.</p>

Analysis of prognostic correlated factors of 49 patients with mucosa-associated lymphoid tissue lymphoma / 中国实验血液学杂志

The aim of this study was to investigate the clinical feature of mucosa-associated lymphoid tissue lymphoma and clarify the relationship between the pathological, clinical features, the expression of API2-MALT1 and the prognosis. A number of factors including pathological characters, grade, stage, prognosis and treatment of 49 cases of MALT lymphoma were analyzed, and the API2-MALT1 rearrangement was detected by RT-PCR. The results showed that 49 patients were diagnosed as MALT lymphoma, in which median age was 52.4 years. The percentage of patients older than 50 years was 67.3%. The majority of tumors were found in stomach (22 cases), intestine (13 cases), thyroid (6 cases) and so on. Among 49 patients, stage I, II was 77. 6%, stage III, IV was 22.4%. API2-MALT1 rearrangement were found 38.1% in low grade, and 12.5% in transform type. Among 18 patients with gastric MALT lymphoma, 9 cases (50.0%) were helicobacter pylori (HP) positive and received antibiotic treatment. The 3 years overall survival was 93.8%. It is concluded that MALT lymphoma is often seen in older patients, most of them were in low grade with slow progression. The site, grade, stage and molecular genetic changes are important prognostic factors, which can contribute to choosing suitable treatment for patients with MALT lymphoma. The antibiotic treatment is effective for patients with positive HP.

Linfoma Malt de Conjuntiva: o diagnóstico ao alcance do primeiro olhar / Conjunctival Malt Lymphoma: diagnosis at first sight

O linfoma de zona marginal extranodal do tecido linfóide associado à mucosa (ou Linfoma MALT) é uma neoplasia linfocitária que surge a partir de qualquer tecido linfóide organizado. Esse linfoma pode acometer diversos órgãos, sendo raro na conjuntiva. Lesões expansivas conjuntivais podem ter vários diagnósticos diferenciais clínicos e histopatológicos, nem todos de histogênese tumoral. Este relato tem como objetivo descrever um caso incomum de tumor na conjuntiva, pouco sintomático, de fácil visibilização e de evolução clínica indolente. São também descritos dados atuais sobre o assunto, com ênfase no comportamento biológico dessas lesões.

The extranodal marginal zone lymphoma of MALT (mucosa-associated lymphoid tissue) is a lymphoproliferative neoplasm that can emerge from any organized lymphoid tissue. This lymphoma can affect many organs, but rarely in conjunctiva. Growing conjunctival lesions may have many differential clinical and histopathological diagnoses and not all of them have a tumor histogenesis. The aim of this article is to describe an interesting, poorly symptomatic, easy to see and indolent conjunctival tumor. Current information on the subject is also given, emphasizing the biological behavior of these lesions.

Detection of API2-MALT1 fusion gene in extranodal B-cell lymphoma and its significance / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the expression of API2-MALT1 mRNA in mucosa-associated lymphoid tissue (MALT) lymphoma, extranodal diffuse large B-cell lymphoma (DLBCL) and Hashimoto's thyroiditis, to investigate the expression pattern of API2-MALT1 variants, and to correlate the findings with the clinicopathologic features and prognosis.</p><p><b>METHODS</b>Sixty-two cases of MALT lymphoma (10 from lung, 31 from stomach, 9 from intestine and 12 from thyroid), 32 cases of extranodal DLBCL (16 from stomach, 13 from intestine and 3 from thyroid), 8 cases of Hashimoto's thyroiditis and 5 cases of reactive lymph nodes hyperplasia as negative controls were collected. The expression of API2-MALT1 mRNA was studied in all cases by reverse transcriptase (RT)-polymerase chain reaction (PCR) and nested PCR. The 94 cases of lymphoma were subdivided into API2-MALT1-positive and API2-MALT1-negative groups. Among the patients, 78 were followed up for 6 to 120 months. The differences in clinicopathologic features and prognosis between the two groups were analyzed.</p><p><b>RESULTS</b>API2-MALT1 transcripts were detected in 39 of the 94 lymphoma cases (with 28 cases being MALT lymphoma and 11 cases being extranodal DLBCL). mRNA expression was not detected in all cases of Hashimoto's thyroiditis and the negative controls. Two fusion gene variants, A1446-M1123 and A1446-M814 were found, and A1446-M1123 expression was more common. As for MALT lymphoma cases, the frequency of the fusion gene expression was lower in thyroid, when compared with that in lung, stomach and intestine. API2-MALT1-positive cases had tumors in an earlier stage with milder infiltration of cancer cells, lower relapse rate, and higher five-year survival rate.</p><p><b>CONCLUSIONS</b>The expression of API2-MALT1 mRNA can be detected in both MALT lymphoma and extranodal DLBCL, but not in Hashimoto's thyroiditis. These cases tend to show a more indolent clinical course and better survival. The frequency of t (11; 18) (q21; q21) correlates with the primary sites of MALT lymphoma. The higher incidence of breakpoint at 1123 bp of MALT1 gene in Chinese people may be due to geographical variation.</p>