Sobrevida del cáncer glótico en estadio inicial en 4 centros hospitalarios de Uruguay

Introducción: El cáncer de laringe es el tumor maligno de mayor prevalencia en la Otorrinolaringología. La topografía glótica es la más frecuente en Uruguay y suele detectarse en estadios tempranos dada la manifestación precoz y sostenida de disfonía. El objetivo de este estudio es describir la sobrevida libre de enfermedad (SLE) y la sobrevida global (SG) de los pacientes con cáncer de laringe glótico en estadio T1N0M0 en 4 instituciones de Montevideo. Metodología: Se analizó de forma retrospectiva la SG y SLE de 55 pacientes diagnosticados con cáncer de glotis T1 entre los años 2009 y 2019. Para el cálculo de la sobrevida se utilizó el método de Kaplan-Meier. Se estudió además el efecto de variables pronósticas de interés sobre la SG mediante análisis univariado y multivariado. Resultados: En la muestra analizada la SG de los pacientes con cáncer glótico T1N0M0 fue como media de 7.706 años (IC 95% 6.63 - 8.78). A los 5 años, la SG fue de 77.5% (± 7%) y de 62% (± 9.8%) a los 10 años. La SLE para todos los pacientes correspondió al 74.6% (± 7.5%) y 63.1% (± 9.8%), a 5 y 10 años respectivamente. No se alcanzaron las medianas de SG ni de SLE para los grupos. Conclusiones: Los valores de SG y SLE medios obtenidos en nuestro medio son comparables a los valores reportados en la bibliografía internacional. No se alcanzó la mediana de SG ni de SLE, por lo que se puede afirmar que ésta enfermedad tiene, cuando se realiza el tratamiento adecuado, un buen pronóstico vital a los 10 años. Se requiere un seguimiento más largo para determinar las medianas de SG y SLE de los grupos en estudio.

Introduction: Laryngeal cancer is the most prevalent malignant tumor in Otorhinolaryngology. Glottic topography is the most frequent in Uruguay and is usually detected in early stages given the early and sustained manifestation of dysphonia. The objective of this study is to analyze disease-free survival (DFS) and overall survival (OS) of patients with stage T1N0M0 glottic laryngeal cancer at 4 institutions in Montevideo. Methodology: The mean OS and DFS of 55 patients diagnosed with T1 glottic cancer between 2009 and 2019 were retrospectively analyzed. Kaplan-Meier method was used to calculate survival. The prognostic effect of certain variables of interest on OS was also studied using univariate and multivariate analysis. Results: In this study, mean odds survival (OS) for T1N0M0 glottic cancer was 7.706 years (CI 95% 6.63 - 8.78). At 5 years, OS was 77.5% (± 7%) and at 10 years was 62% (± 9.8%). Disease free survival (DFS) was 74.6% ± (7.5%) at 5 years and 63.1% (± 9.8%), at 10 years. Median OS and DFS for the groups were not reached. Conclusions: OS and DFS in our medium is comparable to that reported in the international literature. The median OS and DFS were not reached, so it can be stated that this disease has, when appropriate treatment is performed, a good vital prognosis at 10 years. Longer follow-up is required to determine the median OS and DFS of the study groups.

Introdução: O câncer de laringe é o tumor maligno mais prevalente na Otorrinolaringologia. A topografia glótica é a mais frequente no Uruguai e geralmente é detectada em estágios iniciais devido à manifestação precoce e sustentada da disfonia. O objetivo deste estudo é analisar a sobrevida livre de doença (DFS) e a sobrevida global (OS) de pacientes com câncer de laringe glótico estágio T1N0M0 em 4 instituições em Montevidéu. Metodologia: Foram analisados retrospectivamente o OS e DFS de 55 pacientes diagnosticados com câncer glótico T1 entre 2009 e 2019. O método de Kaplan-Meier foi usado para calcular a sobrevida. Resultados: Na amostra, a sobrevida global (OS) do câncer glótico T1N0M0 foi em média de 7.706 anos (IC 95% 6,63 - 8,78). Aos 5 anos, a OS foi de 77,5% (± 7%) e 62% (± 9,8%) aos 10 anos. A DFS para todos os pacientes correspondeu a 74,6% (± 7,5%) e 63,1% (± 9,8%), aos 5 e 10 anos, respectivamente. As medianas de OS e DFS para os grupos não foram alcançadas. Conclusões: OS e DFS em nosso ambiente é comparável ao relatado na literatura internacional. As medianas de SG e SLD não foram alcançadas, pelo que se pode afirmar que esta doença apresenta, quando realizado tratamento adequado, um bom prognóstico vital aos 10 anos. É necessário um acompanhamento mais longo para determinar a mediana da SG e da SLD dos grupos de estudo.

Un desafío terapéutico: la heterorresistencia en Mycobacterium tuberculosis / An emerging problem: heteroresistance in Mycobacterium tuberculosis

Resumen Se considera infección mixta por Mycobacterium tuberculosis (Mtb) a la coexistencia en forma simul tánea y en un mismo paciente de 2 cepas diferentes de Mtb o 2 variantes distintas de la misma cepa. Cuando una de las variantes selecciona mutaciones de resistencia, se denomina heterorresistencia (HTR) monoclonal; en caso de que sean 2 cepas diferentes, una sensible y una resistente (o cepas con diferentes patrones de resistencia), se denomina HTR policlo nal. Se presentan 3 pacientes, HIV/sida, todos con reiterados problemas de adherencia al tratamiento, en los cuales a través de la secuenciación genómica completa de Mtb se diagnosticó HTR monoclonal con coexistencia de 2 variantes de la misma cepa aisladas de muestras de pulmón y ganglios linfáticos, con diferentes perfiles de resistencia en cada uno de los casos. Es importante pensar en la posibilidad de HTR, principalmente en pacientes con múltiples intentos terapéuticos previos y altas poblaciones bacilares, como en el sida avanzado, dado que esta situación compromete potencialmente los resultados del tratamiento al coexistir cepas o variantes de ce pas sensibles y resistentes.

Abstract Mixed infection by Mycobacterium tuberculosis (Mtb) consists in the simultaneous coexistence in the same patient of two different strains of Mtb or 2 different variants of the same strain. When one of the variants selects for resistance mutations, it is called monoclonal heteroresistance (HTR); if there are 2 different strains, one sensitive and one resistant (or with different resis tance patterns), it is called polyclonal HTR. Three cases of HIV/AIDS patients are presented, all with repeated treatment adherence problems, in whom monoclonal HTR was diagnosed through Mtb complete genomic sequentiation with the coexistence of two variants of the same strain isolated from samples from lung and lymph nodes, with different resistance profiles in each case. It is important to consider the possibility of HTR, especially in patients with multiple previous therapeu tic attempts and high bacillary populations, such as in advanced AIDS, since this situation potentially com promises treatment results by coexisting sensitive and resistant variants of a strain (or strains).

[An emerging problem: heteroresistance in Mycobacterium tuberculosis]. / Un desafío terapéutico: la heterorresistencia en Mycobacterium tuberculosis.

Mixed infection by Mycobacterium tuberculosis (Mtb) consists in the simultaneous coexistence in the same patient of two different strains of Mtb or 2 different variants of the same strain. When one of the variants selects for resistance mutations, it is called monoclonal heteroresistance (HTR); if there are 2 different strains, one sensitive and one resistant (or with different resistance patterns), it is called polyclonal HTR. Three cases of HIV/AIDS patients are presented, all with repeated treatment adherence problems, in whom monoclonal HTR was diagnosed through Mtb complete genomic sequentiation with the coexistence of two variants of the same strain isolated from samples from lung and lymph nodes, with different resistance profiles in each case. It is important to consider the possibility of HTR, especially in patients with multiple previous therapeutic attempts and high bacillary populations, such as in advanced AIDS, since this situation potentially compromises treatment results by coexisting sensitive and resistant variants of a strain (or strains).

Se considera infección mixta por Mycobacterium tuberculosis (Mtb) a la coexistencia en forma simultánea y en un mismo paciente de 2 cepas diferentes de Mtb o 2 variantes distintas de la misma cepa. Cuando una de las variantes selecciona mutaciones de resistencia, se denomina heterorresistencia (HTR) monoclonal; en caso de que sean 2 cepas diferentes, una sensible y una resistente (o cepas con diferentes patrones de resistencia), se denomina HTR policlonal. Se presentan 3 pacientes, HIV/sida, todos con reiterados problemas de adherencia al tratamiento, en los cuales a través de la secuenciación genómica completa de Mtb se diagnosticó HTR monoclonal con coexistencia de 2 variantes de la misma cepa aisladas de muestras de pulmón y ganglios linfáticos, con diferentes perfiles de resistencia en cada uno de los casos. Es importante pensar en la posibilidad de HTR, principalmente en pacientes con múltiples intentos terapéuticos previos y altas poblaciones bacilares, como en el sida avanzado, dado que esta situación compromete potencialmente los resultados del tratamiento al coexistir cepas o variantes de cepas sensibles y resistentes.

Controversias en radioterapia adyuvante en cáncer de próstata localizado

La elección del momento más adecuado para realizar radioterapia en el tratamiento del cáncer de próstata es controversial ya que puede ser realizada inmediatamente posterior a la prostatectomía o como tratamiento de rescate ante una recaída. En este artículo, se realiza una búsqueda del tema, se seleccionan los ensayos clínicos con mayor evidencia y se analizan los resultados. Si bien existe beneficio en la radioterapia adyuvante, este resultado no se encuentra en todos los pacientes y sí se asocia a mayor toxicidad genitourinaria tardía, por lo tanto, la clave está en la selección del tratamiento según el paciente específico.

The choice of the most appropriate time to perform radiotherapy in the treatment of prostate cancer is controversial since it can be performed immediately after prostatectomy or as rescue treatment in case of relapse. In this article, a search for the topic is carried out, the clinical trials with the greatest evidence are selected and the results are analyzed. Although there is benefit in adjuvant radiotherapy, this result is not found in all patients and it is associated with greater late genitoutinary toxicity, therefore, the key is in the selection of treatment according to the specific patient.

Tratamiento radiante adyuvante del lecho quirúrgico en el cáncer de mama: a quién, cuándo y cómo hacerlo: Revisión narrativa / Adjuvant radiation treatment of the surgical bed in breast cancer: who, when and how to do it: A narrative review

Introducción: Actualmente existen discrepancias en cuanto a la indicación, dosis, técnica y contorneo de la sobreimpresión o aumento de dosis de irradiación sobre el lecho quirúrgico en el trata-miento adyuvante en cáncer de mama. Propósito de la revisión: El objetivo de la revisión es presentar la evidencia disponible en sobre-impresión del lecho quirúrgico en el tratamiento de cáncer de mama. Realizamos una revisión bibliográfica en MEDLINE pubmed, se analizaron 61 estudios publicados entre enero del 2000 a enero del 2022. Recientes hallazgos: La sobreimpresión sobre el lecho quirúrgico en la mama mejora el control local en aquellas pacientes con elementos de alto riesgo. Las diferentes técnicas disponibles son oncológicamente equivalentes. La delimitación del blanco de tratamiento debe guiarse por los clips quirúrgicos. Conclusiones: La indicación de dicho tratamiento deberá ser evaluado por los servicios de oncología radioterápica, definiendo sus protocolos y algoritmos de acción.

Introduction: Currently, there are discrepancies regarding the indication, dose, technique, and con-touring of the super impression or increase in irradiation dose on the surgical bed in adjuvant treatment in breast cancer. Purpose of the review: The objective is to present evidence on superimposing the surgical bed to treat breast cancer. We conducted a bibliographic review in MEDLINE PubMed; 61 studies published between January 2000 and January 2022 were analyzed. Recent findings: Superimpression of the surgical bed in the breast improves local control in patients with high-risk elements. The different techniques available are oncologically equivalent, and the surgical clips should guide the delineation of the treatment target. Conclusions: The indication of this treatment must be evaluated by radiotherapy oncology services, defining their protocols and action algorithms.

The sternum reconstruction: Present and future perspectives.

Sternectomy is a procedure mainly used for removing tumor masses infiltrating the sternum or treating infections. Moreover, the removal of the sternum involves the additional challenge of performing a functional reconstruction. Fortunately, various approaches have been proposed for improving the operation and outcome of reconstruction, including allograft transplantation, using novel materials, and developing innovative surgical approaches, which promise to enhance the quality of life for the patient. This review will highlight the surgical approaches to sternum reconstruction and the new perspectives in the current literature.

Automated identification of sequence-tailored Cas9 proteins using massive metagenomic data.

The identification of the protospacer adjacent motif (PAM) sequences of Cas9 nucleases is crucial for their exploitation in genome editing. Here we develop a computational pipeline that was used to interrogate a massively expanded dataset of metagenome and virome assemblies for accurate and comprehensive PAM predictions. This procedure allows the identification and isolation of sequence-tailored Cas9 nucleases by using the target sequence as bait. As proof of concept, starting from the disease-causing mutation P23H in the RHO gene, we find, isolate and experimentally validate a Cas9 which uses the mutated sequence as PAM. Our PAM prediction pipeline will be instrumental to generate a Cas9 nuclease repertoire responding to any PAM requirement.

Exosomal telomerase transcripts reprogram the microRNA transcriptome profile of fibroblasts and partially contribute to CAF formation.

It is now well accepted that cancer cells change their microenvironment from normal to tumor-supportive state to provide sustained tumor growth, metastasis and drug resistance. These processes are partially carried out by exosomes, nano-sized vesicles secreted from cells, shuttled from donor to recipient cells containing a cargo of nucleic acids, proteins and lipids. By transferring biologically active molecules, cancer-derived exosomes may transform microenvironmental cells to become tumor supportive. Telomerase activity is regarded as a hallmark of cancer. We have recently shown that the transcript of human telomerase reverse transcriptase (hTERT), is packaged in cancer cells derived- exosomes. Following the engulfment of the hTERT transcript into fibroblasts, it is translated into a fully active enzyme [after assembly with its RNA component (hTERC) subunit]. Telomerase activity in the recipient, otherwise telomerase negative cells, provides them with a survival advantage. Here we show that exosomal telomerase might play a role in modifying normal fibroblasts into cancer associated fibroblasts (CAFs) by upregulating [Formula: see text]SMA and Vimentin, two CAF markers. We also show that telomerase activity changes the transcriptome of microRNA in these fibroblasts. By ectopically expressing microRNA 342, one of the top identified microRNAs, we show that it may mediate the proliferative phenotype that these cells acquire upon taking-up exosomal hTERT, providing them with a survival advantage.

The role of Ivor Lewis esophagectomy in the treatment of achalasia with megaesophagus: A case report.

Introduction: Achalasia with megaesophagus is a pathology characterized by widespread and irregular dilation of the esophageal lumen. In most cases, this dilation is caused by contraction and subsequent failed relaxation of the lower esophageal sphincter (LES). It may be associated with a partial or complete slowing of the esophageal peristalsis. Case overview: We present the case of a 58-year-old woman who developed dysphagia, regurgitation, and substantial weight loss (11 kg) over a span of 1 year. Symptomatic achalasia with megaesophagus was diagnosed following chest and abdominal computed tomography (CT) with contrast and transit RX with gastrografin and esophageal manometry. The patient refuse all minimally endoscopic treatments and opted straightly for the treatment with esophagectomy sec. Ivor-Lewis. At the 6-month follow-up, the patient appeared in excellent general clinical condition and oral gastrografin radiography (OGR) showed good channeling. Discussion: Patients require medical attention when presenting with achalasia that has eroded the esophageal wall enough to form a megaesophagus. Early and minimally invasive treatments (i.e., medical therapy, endoscopic dilation, and myotomy) are insufficient at this stage, and thus esophageal surgery is required. Among the most common surgical approaches, we must mention esophagectomy sec. McKeown and esophagectomy with interposition of a colic loop sec. Wilkins; however, based on our experience, esophagectomy sec. Ivor-Lewis with intrathoracic anastomosis leads to excellent results and can therefore be considered a valid alternative for treating complex cases. Conclusions: Subtotal esophagectomy sec. Ivor-Lewis with intrathoracic anastomosis is effective in treating achalasia with megaesophagus.

Primario desconocido de cabeza y cuello, una visión del oncólogo radioterapeuta / Unknown primary of the head and neck, a vision of the radiation oncologist

Se define carcinoma de cabeza y cuello (CCC) de primario desconocido al cuadro de adenopatía cervical en que, luego de examen físico, estudios de imágenes y panendoscopía con biopsias, no se encuentra el tumor primario pero sí la confirmación de malignidad de la adenomegalia. Son infrecuentes, por lo que estudios prospectivos que arrojen resultados estadísticamente significativos no están disponibles actualmente, y el tratamiento definitivo es aún motivo de controversia. Al ser la radioterapia un tratamiento dirigido es imprescindible definir adecuadamente los volúmenes blanco de tratamiento; es ideal el hallazgo del tumor primario, pero en muchos casos a pesar de un estudio escalonado, exhaustivo y multidisciplinar esto no se logra. Esto motiva el debate de qué regiones tratar, dosis, fraccionamiento y modalidad (exclusiva, adyuvante, en concurrencia). Hasta el momento el tratamiento de ganglios cervicales y mucosa de alto riesgo parece ser la estrategia con mejor control locorregional.

Head and neck carcinoma (HNC) of unknown primary is a clinical condition defined as a cervical adenopathy for which, after physical examination, imaging studies and panendoscopy with biopsies, the primary tumor is not found, but there is confirmed malignancy of the adenomegaly. It is infrequent, so prospective studies that yield statistically significant results are not currently available, and definitive treatment is still controversial. Since radiation therapy is a targeted treatment, it is essential to adequately define treatment target volumes; the discovery of the primary tumor is ideal, but in many cases, despite a phased, exhaustive and multidisciplinary study, this is not achieved. This motivates the debate on which regions to treat, dose, fractionation and modality (exclusive, adjuvant, concurrent). Until now, the treatment of high-risk cervical nodes and mucosa seems to be the strategy with the best locoregional control.

The success of Eso-SPONGE® therapy in the treatment of anastomotic dehiscence after Ivor-Lewis subtotal esophagectomy: A case report.

INTRODUCTION: Eso-SPONGE® has proved to be an excellent method for the treatment of persistent dehiscence of the intrathoracic esophagogastric anastomosis during the operation of subtotal esophagectomy sec. Ivor Lewis. CLINICAL CASE PRESENTATION: The case presented is of a 72-year-old patient with esophageal adenocarcinoma (ADK) who underwent sub-total esophagectomy and esophagoplasty sec. Ivor Lewis complicated by an esophageal leak. The Eso-SPONGE® therapy has been successful halving the index of inflammation after the first two sessions and generation of a neowall after seven sessions. DISCUSSION: Eso-SPONGE® therapy has proven to be a valuable resource as a treatment for esophageal anastomotic dehiscences because it is easily repeatable in suburban centers, provided that they have a digestive endoscopy specialized in the positioning process. CONCLUSIONS: Eso-SPONGE® is a minimally invasive method that delivers excellent results in the treatment of fragile patients, such as those who have post-esophageal anastomotic dehiscence.

Protein self-entanglement modulates successful folding to the native state: A multi-scale modeling study.

The computer-aided investigation of protein folding has greatly benefited from coarse-grained models, that is, simplified representations at a resolution level lower than atomistic, providing access to qualitative and quantitative details of the folding process that would be hardly attainable, via all-atom descriptions, for medium to long molecules. Nonetheless, the effectiveness of low-resolution models is itself hampered by the presence, in a small but significant number of proteins, of nontrivial topological self-entanglements. Features such as native state knots or slipknots introduce conformational bottlenecks, affecting the probability to fold into the correct conformation; this limitation is particularly severe in the context of coarse-grained models. In this work, we tackle the relationship between folding probability, protein folding pathway, and protein topology in a set of proteins with a nontrivial degree of topological complexity. To avoid or mitigate the risk of incurring in kinetic traps, we make use of the elastic folder model, a coarse-grained model based on angular potentials optimized toward successful folding via a genetic procedure. This light-weight representation allows us to estimate in silico folding probabilities, which we find to anti-correlate with a measure of topological complexity as well as to correlate remarkably well with experimental measurements of the folding rate. These results strengthen the hypothesis that the topological complexity of the native state decreases the folding probability and that the force-field optimization mimics the evolutionary process these proteins have undergone to avoid kinetic traps.

Patogenia y tratamiento de la mucositis asociada al tratamiento de radioterapia y/o quimioterapia en pacientes con cáncer de cabeza y cuello / Pathogenesis and treatment of mucositis associated with radiotherapy and / or chemotherapy treatment in patients with head and neck cancer / Patogênese e tratamento da mucosite associada ao tratamento com radioterapia e / ou quimioterapia em pacientes com câncer de cabeça e pescoço

Resumen: La mucositis es un efecto adverso frecuente e invalidante en los pacientes oncológicos que reciben tratamiento de Radioterapia y Quimioterapia a altas dosis y muchas veces lleva a la suspensión del tratamiento. Si bien es una entidad que tiene gran relevancia en los pacientes e importante impacto económico en las instituciones de salud, no existen tratamientos claramente establecidos ni eficaces para mejorar esta condición. El objetivo de esta revisión es analizar la evidencia disponible en el tratamiento de la mucositis, y el respaldo científico e impacto que tienen conductas habitualmente tomadas en su tratamiento.

Abstract: Mucositis is a frequent and disabling adverse effect in cancer patients who received radiation therapy and chemotherapy at high doses and often discontinues treatment. Although it is an entity that has great relevance in patients and an important economic impact in health institutions, there are no clearly established or modified treatments to improve this condition. The objective of this review is to analyze the available evidence in the treatment of mucositis, and the scientific support and impact of behaviors commonly taken in its treatment.

Resumo: A mucosite é um efeito adverso frequente e incapacitante em pacientes com câncer que receberam radioterapia e quimioterapia em altas doses e muitas vezes interrompe o tratamento. Embora seja uma entidade que tenha grande relevância nos pacientes e um importante impacto econômico nas instituições de saúde, não existem tratamentos claramente estabelecidos ou modificados para melhorar essa condição. O objetivo desta revisão é analisar as evidências disponíveis no tratamento da mucosite, o suporte científico e o impacto das condutas comumente adotadas no seu tratamento.

Patterns of pharmacological maintenance treatment in a community mental health services bipolar disorder cohort study (SIN-DEPRES).

Maintenance therapy in bipolar disorder (BD) is usually required to prevent relapses and improve residual symptoms. Therefore, in this study, we describe patterns of pharmacological maintenance treatment and identify associated clinical features. This prospective multicentre epidemiological study recruited a cohort of 739 consecutive out-patients with clinically stable BD. Clinical stability was assessed at baseline with the Clinical Global Impression scale for BD and depressive symptoms with the Hamilton Depression Rating Scale. Psychotropic medications were classified and analysed according to their mechanism as well as use. Logistic regression models were used to examine the associations between pharmacological strategies and clinical features. Longer time since last episode [odds ratio (OR) 1.002, p < 0.0001] and family history of psychiatric disorders (OR 1.911, p = 0.028) were associated with lithium in monotherapy; manic polarity of the most recent episode (OR 3.300, p = 0.006) and longer duration of clinical stability (OR 1.009, p = 0.034) with antipsychotic in monotherapy; depressive polarity of the most recent episode (OR 2.567, p = 0.003) and bipolar II disorder diagnosis (OR 2.278, p = 0.008) with antidepressant combination; no ongoing psychiatric co-morbidity (OR 0.230, p = 0.004) with lithium and anticonvulsant; manic polarity of the most recent episode (OR 3.774, p < 0.0001) with lithium and antipsychotic; manic polarity of the most recent episode (OR 2.907, p = 0.028) with lithium, anticonvulsant and antipsychotic. The pharmacological patterns followed published recommendations, except for the excessive use of antidepressants. This study reveals clinical factors closely related to prescription patterns.