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Introduction Gastrointestinal stromal tumors (GISTs) are neoplasms originating from the interstitial cells of Cajal, pacemaker cells responsible for intestinal motility. Patients with locally advanced GISTs and those with borderline resections due to the proximity of vital anatomical structures, which could result in unacceptable post-surgical morbidity, require special therapeutic consideration. Imatinib, a tyrosine kinase inhibitor, has demonstrated significant success in the non-surgical management of metastatic GIST, and its favorable impact on overall survival in the adjuvant setting makes it logical to speculate on the benefit it could provide as a neoadjuvant medication in patients with locally advanced disease. Methods Patients aged 18-90 years with a diagnosis of GIST confirmed by immunohistochemistry (CD117 positivity) who were treated at the Oncology Hospital of Centro Médico Nacional Siglo XXI in Mexico City from January 2012 to December 2016 were included in the study. It is a retrospective study with a duration of four years. Clinical data were collected from the medical records, which included sex, age, tumor location, initial resectability, reason for unresectability, initial tumor size, and mitotic rate. In the case of unresectable disease, patients who were evaluated by medical oncology and who had received treatment with 400 mg of imatinib daily were evaluated. Results A total of 312 patients diagnosed with GIST were analyzed. One hundred thirty-one were men (42%) with a mean age of 57 years, and 181 were women (58%) with a mean age of 59 years. The most frequent anatomical location was the stomach (n=185, 59.2%). At the time of diagnosis, 210 patients (67.3%) presented with resectable disease, while n=102 patients (32.7%) had unresectable disease. A total of 102 patients with unresectable disease received therapy with 400 mg of imatinib per day. Sixteen patients (15.7%) presented a reduction in tumor dimensions and underwent surgery. Conclusion The study highlights the importance of complete surgical resection and the potential benefit of neoadjuvant imatinib therapy in converting unresectable to resectable disease. The results suggest that imatinib can be effective in converting unresectable GISTs to resectable ones, allowing for a complete resection to be performed and obtaining an R0 resection in 93.7% of these cases.

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Gastrointestinal stromal tumors (GISTs) are sarcomas affecting the stomach and small intestine, with a rare subtype characterized by succinate dehydrogenase B (SDHB)-loss posing significant diagnostic and therapeutic challenges. A 62-year-old man with weight loss and abdominal pain was diagnosed with a gastric GIST showing SDHB-loss. Initial treatment with Imatinib reduced the tumor size, but surgery revealed no residual tumor. Despite adjuvant Imatinib, recurrence occurred, necessitating further surgical intervention. While GISTs typically benefit from surgery and tyrosine kinase inhibitors (TKIs), those with SDHB-loss are resistant to TKIs, requiring a different management approach. This case emphasizes the importance of surgical intervention for SDHB-deficient GISTs and the need for ongoing research into effective treatments for this subtype.

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Background Gastrointestinal stromal tumors (GISTs) arise from Cajal's interstitial cell precursors and display a variety of genetic mutations, primarily in the KIT and PDGFRA genes. These mutations are linked to tumor location, prognosis, and response to treatment. This study delves into the mutational patterns of GISTs in a Mexican population and their impact on overall survival (OS) and disease-free survival (DFS). Methodology This retrospective study examined 42 GIST cases diagnosed at the Oncology Hospital of the National Medical Center XXI Century between January 2018 and December 2020. Clinical, histological, and immunohistochemical data were gathered, and mutational analysis of KIT and PDGFRA genes was conducted using second-generation sequencing. Results The study group consisted of 52.4% females and 47.6% males, with an average age of 62.6 years. The most common tumor site was the stomach (59.5%), followed by the small intestine (26.2%). KIT mutations were detected in 71.4% of cases, predominantly involving exon 11. PDGFRA mutations were observed in 7.1% of cases. Recurrence was noted in 9.5% of patients, all with high-risk tumors. No significant link was identified between specific mutations and OS or DFS. Conclusions This investigation sheds light on the genetic landscape of GISTs in the Mexican population. While no significant association was established between particular mutations and survival outcomes, the study emphasizes the importance of molecular profiling in treatment decision-making. Further studies with larger sample sizes and longer follow-up periods are necessary to validate these results and explore their clinical relevance.

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INTRODUCTION: The critical role of microRNA-128 (miR-128) in gastrointestinal-related diseases has been documented. In the current study, we tried to clarify the specific role miR-128 in gastrointestinal stromal tumor (GIST) and the underlying mechanism. METHODS: Differentially expressed genes in GIST were identified following bioinformatics analysis. Then, expression patterns of miR-128 and B-lymphoma Mo-MLV insertion region 1 (BMI-1) in clinical tissue samples and cell lines were characterized, followed by validation of their correlation. GIST-T1 cells were selected and transfected with different mimic, inhibitor, or siRNA plasmids, after which the biological functions were assayed. RESULTS: We identified low miR-128 and high BMI-1 expression in GIST tissues of 78 patients and 4 GIST cell lines. Ectopic expression of miR-128 or silencing of BMI-1 suppressed the malignant potentials of GIST-T1 cells. As a target of miR-128, BMI-1 re-expression could partly counteract the suppressive effect of miR-128 on the malignancy of GIST-T1 cells. CONCLUSION: Our study provided evidence that miR-128-mediated silencing of BMI-1 could prevent malignant progression of GIST, highlighting a promising anti-tumor target for combating GIST.

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BACKGROUND: Gastrointestinal stromal tumors (GIST) represent a significant clinical challenge due to their metastatic potential and limited treatment options. Raf kinase inhibitor protein (RKIP), a suppressor of the MAPK signaling pathway, is downregulated in various cancers and acts as a metastasis suppressor. Our previous studies demonstrated low RKIP expression in GIST and its association with poor outcomes. This study aimed to expand on the previous findings and investigate the biological and therapeutic implications of RKIP loss on GIST. METHODS: To validate the RKIP prognostic significance, its expression was evaluated by immunohistochemistry in 142 bona fide GIST cases. The functional role of RKIP was evaluated in vitro, using the GIST-T1 cell line, which was knocked out for RKIP. The biological and therapeutic implications of RKIP were evaluated by invasion, migration, apoptosis, and 2D / 3D viability assays. Additionally, the transcriptome and proteome of RKIP knockout cells were determined by NanoString and mass spectrometry, respectively. RESULTS: Immunohistochemical analysis revealed the absence of RKIP in 25.3% of GIST cases, correlating with a tendency toward poor prognosis. Functional assays demonstrated that RKIP knockout increased GIST cells' invasion and migration potential by nearly 60%. Moreover, we found that RKIP knockout cells exhibited reduced responsiveness to Imatinib treatment and higher cellular viability in 2D and 3D in vitro models, as assessed by apoptosis-related protein expression. Through comprehensive genetic and proteomic profiling of RKIP knockout cells, we identified several putative RKIP-regulated proteins in GIST, such as COL3A1. CONCLUSIONS: Using a multidimensional integrative analysis, we identified, for the first time in GIST, molecules and pathways modulated by RKIP that may potentially drive metastasis and, consequently, poor prognosis in this disease.

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Introduction: Subepithelial lesions (SELs), described as bulges or masses covered by healthy-looking mucosa, are usually found incidentally during endoscopic studies. They are typically asymptomatic and are estimated to be identified in 1% of esophagogastroduodenoscopies performed. Materials and methods: A descriptive study was conducted with retrospective data collection. We included all patients treated at the Unión de Cirujanos, a referral gastroenterology unit of the Coffee Region in Manizales, between January 2020 and January 2022, who underwent endoscopic ultrasonography to study subepithelial-looking lesions located in the esophagus, stomach, and duodenum. Results: 152 endoscopic ultrasounds were performed, finding 108 SELs; 66.6% of the patients were women, and the average age was 58. Most SELs were located in the stomach (78.7%), the antrum being the most frequent location. The average diameter of the gastric SELs was 14.6 mm, and 47% of the lesions depended on the fourth echolayer; the most frequent presumptive diagnoses were gastrointestinal stromal tumor (GIST; 65.8%) and lipoma (11.7%). Conclusions: SELs of the GI tract originate in the muscularis mucosae, submucosa, or muscularis propria. They are most frequently located in the stomach, and their characterization usually requires endoscopic ultrasonography and histopathology. Treatment of these lesions remains controversial due to their low frequency, histological variety, and low malignant potential.

Introducción: las lesiones subepiteliales (LSE), descritas como abultamientos o masas cubiertas por mucosa de aspecto sano, se encuentran usualmente de manera incidental durante estudios endoscópicos; suelen ser asintomáticas y se estima que se identifican en el 1% de las esofagogastroduodenoscopias realizadas. Métodos: se realizó un estudio descriptivo con recolección retrospectiva de la información. Se incluyeron todos los pacientes atendidos en Unión de Cirujanos, unidad de gastroenterología de referencia del Eje Cafetero ubicada en la ciudad de Manizales, entre enero de 2020 y enero de 2022, a quienes se les realizó ultrasonografía endoscópica como parte del estudio de lesiones de aspecto subepitelial localizadas en el esófago, estómago y duodeno. Resultados: se realizaron 152 endosonografías y se encontraron 108 lesiones subepiteliales, 66,6% de los pacientes eran mujeres y el promedio de edad fue 58 años. La mayoría de las LSE se localizaron en el estómago (78,7%) y, de estas, la localización más frecuente fue el antro; el diámetro promedio de las LSE gástricas fue de 14,6 mm y el 47% de las lesiones eran dependientes de la cuarta ecocapa; los diagnósticos presuntivos más frecuentes fueron el tumor del estroma gastrointestinal (GIST; 65,8%) y lipoma (11,7%). Conclusiones: las LSE del tracto gastrointestinal se originan en la muscular de la mucosa, submucosa o muscular propia, de manera más frecuente se localizan en el estómago y su caracterización suele requerir la realización de ultrasonografía endoscópica y estudio histopatológico. El tratamiento de estas lesiones sigue siendo controversial debido a su baja frecuencia, variedad histológica y bajo potencial maligno.

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Gastrointestinal stromal tumor (GIST) is the most common malignant neoplasm of mesenchymal origin, and a paradigmatic model for a successful rational development of targeted therapies in cancer. The introduction of tyrosine kinase inhibitors with activity against KIT/PDGFRA in both localized and advanced stages has remarkably improved the survival in a disease formerly deemed resistant to all systemic therapies. These guidelines are elaborated by the conjoint effort of the Spanish Society of Medical Oncology (SEOM) and the Spanish Sarcoma Research Group (GEIS) and provide a multidisciplinary and updated consensus for the diagnosis and treatment of GIST patients. We strongly encourage that the managing of these patients should be performed within multidisciplinary teams in reference centers.

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Fuzzy-trace theory predicts that decisionmakers process numerical information about risk at multiple levels in parallel: the simplest level, nominal (categorical some-none) gist, and at more fine-grained levels, involving relative comparison (ordinal less-more gist) and exact quantities (verbatim representations). However, little is known about how individual differences in these numerical representations relate to judgments and decisions, especially involving health tradeoffs and relative risks. To investigate these differences, we administered measures of categorical and ordinal gist representations of number, objective numeracy, and intelligence in two studies (Ns = 978 and 956). In both studies, categorical and ordinal gist representations of number predicted risk judgments and decisions beyond objective numeracy and intelligence. Participants with higher scores in categorical gist were more likely to choose options to avoid cancer recurrence risks; those who were higher in ordinal gist of numbers were more likely to discriminate relative risk of skin cancer; and those with higher scores in objective numeracy were more likely to choose options that were numerically superior overall in terms of relative risk of skin cancer and of genetic risks of breast cancer (e.g., lower numerical probability of cancer). Results support parallel-processing models that assume multiple representations of numerical information about risk, which vary in precision, and illustrate how individual differences in numerical representations are relevant to tradeoffs and risk comparisons in health decisions. These representations cannot be reduced to one another and explain psychological variations in risk processing that go beyond low versus high levels of objective numeracy.

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Abstract In view of the morphological similarity between gastrointestinal stromal tumors (GIST) and other sarcomas of the intestine of dogs, the aim was to carry out the histomorphological and immunohistochemical diagnosis of these tumors, associating breed, sex and age, location and tumor invasion. 217 cases were evaluated by histopathology and 36 diagnosed by immunohistochemistry were included (24 GIST and 12 other intestinal sarcomas). Mixed breed dogs were the most diagnosed with GIST, mainly elderly females (9.5±2.2 years); in the other intestinal sarcomas, crossbreeds and Dachshunds, males and females, were equally affected. The cecum was the most affected by GISTs, with tumor invasion of the intestinal layers in all cases. The small intestine was the most affected by the other intestinal sarcomas, with invasion of the layers in most of these tumors. GISTs expressed markers such as CD117 and DOG-1, unlike other intestinal sarcomas. GIST and other intestinal sarcomas denoted histomorphological and immunophenotypic characteristics similar to histopathology, justifying the association of immunohistochemistry for the definitive diagnosis.

Resumo Tendo em vista a semelhança morfológica entre tumores estromais gastrointestinais (GIST) e outros sarcomas do intestino de cães, objetivou-se realizar o diagnóstico histomorfológico e imunoistoquímico desses tumores, associando raça, sexo e idade, localização e invasão tumoral. Foram avaliados 217 casos por histopatologia e incluídos 36 diagnosticados por imuno-histoquímica (24 GIST e 12 outros sarcomas intestinais). Cães sem raça definida foram os mais diagnosticados com GIST, principalmente fêmeas idosas (9,5±2,2 anos); nos demais sarcomas intestinais, mestiços e Dachshunds, machos e fêmeas, foram igualmente acometidos. O ceco foi o mais acometido pelos GISTs, com invasão tumoral das camadas intestinais em todos os casos. O intestino delgado foi o mais acometido pelos demais sarcomas intestinais, com invasão das camadas na maioria desses tumores. GISTs expressaram marcadores como CD117 e DOG-1, ao contrário de outros sarcomas intestinais. O GIST e outros sarcomas intestinais denotaram características histomorfológicas e imunofenotípicas semelhantes à histopatologia, justificando a associação da imuno-histoquímica para o diagnóstico definitivo.

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Introducción. Los tumores del estroma gastrointestinal (GIST) son neoplasias de tejido blando (sarcomas) originados en el sistema gastrointestinal (células intersticiales de Cajal). Se presentan mayormente en el estómago y el intestino delgado. La introducción del imatinib en el tratamiento ha cambiado el pronóstico de esta enfermedad. Objetivo. Describir las características clínicas, biológicas y la respuesta al tratamiento con imatinib de pacientes bolivianos con GIST. Material y métodos. Estudio descriptivo transversal de tipo retrospectivo de pacientes con diagnóstico de GIST (n=9) remitidos entre marzo de 2012 a julio de 2022. Se recopiló y analizó datos demográficos, clínicos y laboratoriales de pacientes con estudio imnunohistoquímica positivos para GIST (CD117, CD34, mutación PDGFRA) que posterior a cirugía recibieron tratamiento con imatinib dentro del programa asistencial GIPAP. Se consideró criterios SWOG y signos de desaparición del tumor para evaluar la respuesta y remisión completa. Resultados. La media de edad de los pacientes (4 mujeres, 5 varones) fue 56 años. Los sitios primarios del GIST fueron el estómago e intestino, 56 % de pacientes presentó tumor >10 cm de diámetro, y 78 % metástasis (peritoneo e hígado). Todos los pacientes alcanzaron remisión completa tras el primer año de tratamiento. Dos pacientes presentaron recaída después de abandonar el tratamiento tras 4 y 8 años respectivamente; uno de ellos reflejó una segunda remisión tras reiniciar tratamiento. Conclusiones. Los datos epidemiológicos son similares a los reportados en otros trabajos,empero un diagnóstico en estadios avanzados y abandono del tratamiento aun tratándose de un programa de tratamiento gratuito constituyen variables diferenciales. Más allá del desconocimiento, la negligencia e irresponsabilidad de los pacientes resulta preocupante.

Introduction. Gastrointestinal stromal tumor (GIST) are mesenchymal neoplasms (sarcomas) in the gastrointestinal tract (interstitial cells of Cajal). It occurs mostly in the stomach and small intestine. The introduction of imatinib for GIST treatment has changed the prognosis of this disease. Objective. To describe the clinical and biological characteristics, and the treatment response to imatinib in Bolivian patients with GIST. Material and methods. Retrospective descriptive cross-sectional study of patients with GIST(n=9) referred between March 2012 and July2022. It was collected demographic, clinical, and laboratory data of patients with immunohistochemical study positive for GIST (CD117, CD34, PDGFRA mutation) who after surgery received treatment with imatinib within the GIPAP program. SWOG criteria and signs of tumor vanishing were considered to assess treatment response and complete remission. Results. The mean age of patients (4 women, 5 men) was 56 years. Primary sites of GIST were the stomach and intestine, 56% of patients presented tumor >10 cm in diameter, and 78% metastasis (peritoneum and liver). All patients achieved complete remission after the first year of treatment. Two patients presented relapse after discontinuing treatment, with a follow-up 4 and 8 years respectively; one of them reflected a second remission after restarting treatment. Conclusions. These epidemiological data are similar to those reported in other studies, however a late-stages diagnosis and treatment dropout, even when trying a free treatment program, constitute differential variables. Beyond misinformation, patients' neglect and irresponsibility is worrying.