RESUMEN
During tumor development, constant interplay occurs between tumor cells and surrounding stromal cells. We report evidence that gastrointestinal stromal tumor (GIST) cells invade the interstitial stroma through the release of the oncogenic protein tyrosine kinase (KIT)-containing exosomes, which triggers the phenotypic conversion of progenitor smooth muscle cells to tumor-promoting cells. These recipient cells display morphologic changes and acquire tumor-associated phenotypes, including enhanced adhesion to extracellular matrix proteins, activation of intracellular pathways downstream of KIT, expression of Interstitial Cell of Cajal-like markers, and release of various matrix metalloproteinases (MMPs), particularly MMP1. This report shows stimulation of MMP1 production by stromal cells via uptake of tumor-derived exosomes, which leads to tumor cell invasion. Exosomes derived from GIST patients but not healthy donors show enhanced MMP1 secretion by smooth muscle cells and tumor cell invasion, whereas selective blocking of exosome-mediated MMP1 secretion decreases tumor invasiveness. Our study indicates that exosome release and subsequent MMP1 induction creates a positive feedback mechanism established between tumor and stromal cells that drives GIST development and offers unique insights for potential therapeutic strategies to block GIST progression and metastatic spread.
Asunto(s)
Exosomas/fisiología , Tumores del Estroma Gastrointestinal/fisiopatología , Metaloproteinasa 1 de la Matriz/metabolismo , Invasividad Neoplásica/fisiopatología , Proteínas Proto-Oncogénicas c-kit/metabolismo , Western Blotting , Línea Celular Tumoral , Cartilla de ADN/genética , Exosomas/metabolismo , Citometría de Flujo , Humanos , Microscopía Electrónica de Transmisión , Microscopía Fluorescente , Nanopartículas/análisis , Interferencia de ARN , ARN Interferente Pequeño/genética , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
New treatment targets need to be identified in gastrointestinal stromal tumors (GISTs) to extend the treatment options for patients experiencing failure with small-molecule tyrosine kinase inhibitors, such as imatinib. Insulin-like growth factor (IGF)-II acts as an autocrine factor in several tumor types by binding to IGF receptor type 1 (IGF-1R) and/or the insulin receptor (IR) isoform A. The aim of the present study was to investigate the putative role of unprocessed pro-IGF-II, called 'big'-IGF-II, in GISTs. The imatinib-sensitive GIST882 and imatinib-resistant GIST48 cell lines secrete high levels of big-IGF-II as demonstrated by ELISA and Western blotting analyses. IR isoform A mRNA and protein expression, but not that of IGF-1R, was found in these KIT mutant cell lines and in KIT and platelet-derived growth factor receptor α-mutant GIST specimens. Down-regulation of either big-IGF-II or IR affected AKT and MAPK signaling and reduced survival in both cell lines. Disruption of big-IGF-II signaling in combination with imatinib had additive cytotoxic effects on GIST882 cells. IGF-II mRNA as determined by in situ hybridization was present in 91% of 60 primary GISTs. Immunohistochemical analysis of big-IGF-II protein expression was associated with moderate- to high-risk tumors compared with tumors with a lower risk classification (P < 0.028). Our data put forth the big-IGF-II/IR isoform A axis as an autocrine survival pathway and potential therapeutic target in GISTs.
Asunto(s)
Tumores del Estroma Gastrointestinal/fisiopatología , Factor II del Crecimiento Similar a la Insulina/fisiología , Precursores de Proteínas/fisiología , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/farmacología , Comunicación Autocrina/efectos de los fármacos , Comunicación Autocrina/fisiología , Benzamidas , Muerte Celular/efectos de los fármacos , Muerte Celular/fisiología , Supervivencia Celular/fisiología , Regulación hacia Abajo/fisiología , Femenino , Tumores del Estroma Gastrointestinal/metabolismo , Tumores del Estroma Gastrointestinal/patología , Humanos , Mesilato de Imatinib , Factor II del Crecimiento Similar a la Insulina/metabolismo , Masculino , Persona de Mediana Edad , Proteínas de Neoplasias/metabolismo , Piperazinas/farmacología , Precursores de Proteínas/metabolismo , Pirimidinas/farmacología , Receptor IGF Tipo 1/metabolismo , Receptor de Insulina/metabolismo , Células Tumorales Cultivadas , Adulto JovenRESUMEN
The patient was an 82-year-old man who had undergone resection of a gastrointestinal stromal tumor(GIST)of the small intestine in January 2000, when he was 69 years old. As peritoneal recurrences were diagnosed in June 2002, we performed peritoneal tumorectomy twice, and the perirectal tumor was controlled with imatinib for over 7 years. Resistance to imatinib was diagnosed in March 2011, and treatment was switched to sunitinib. Administration of sunitinib was started at 50mg/day for 28 days followed by treatment withdrawal for 14 days; however, the dose needed to be reduced twice and then discontinued owing to the occurrence of side effects and pemphigoid. During discontinuation of sunitinib, the tumor increased in size and cancer pain appeared; therefore, sunitinib was re-administered at a very low-dose of 12.5mg every alternate day. Low dose sunitinib was effective; the perirectal tumor was reduced and cancer pain disappeared.
Asunto(s)
Antineoplásicos/uso terapéutico , Resistencia a Antineoplásicos , Tumores del Estroma Gastrointestinal/tratamiento farmacológico , Indoles/uso terapéutico , Neoplasias Intestinales/tratamiento farmacológico , Intestino Delgado , Pirroles/uso terapéutico , Anciano de 80 o más Años , Antineoplásicos/administración & dosificación , Benzamidas , Tumores del Estroma Gastrointestinal/fisiopatología , Tumores del Estroma Gastrointestinal/secundario , Humanos , Mesilato de Imatinib , Indoles/administración & dosificación , Neoplasias Intestinales/patología , Neoplasias Intestinales/cirugía , Intestino Delgado/cirugía , Masculino , Neoplasias Peritoneales/tratamiento farmacológico , Neoplasias Peritoneales/secundario , Neoplasias Peritoneales/cirugía , Piperazinas , Pirimidinas , Pirroles/administración & dosificación , Recurrencia , Terapia Recuperativa , SunitinibRESUMEN
Ano1 is a recently discovered Ca(2+)-activated Cl(-) channel expressed on interstitial cells of Cajal (ICC) that has been implicated in slow-wave activity in the gut. However, Ano1 is expressed on all classes of ICC, even those that do not contribute to generation of the slow wave, suggesting that Ano1 may have an alternate function in these cells. Ano1 is also highly expressed in gastrointestinal stromal tumors. Mice lacking Ano1 had fewer proliferating ICC in whole mount preparations and in culture, raising the possibility that Ano1 is involved in proliferation. Cl(-) channel blockers decreased proliferation in cells expressing Ano1, including primary cultures of ICC and in the pancreatic cancer-derived cell line, CFPAC-1. Cl(-) channel blockers had a reduced effect on Ano1(-/-) cultures, confirming that the blockers are acting on Ano1. Ki67 immunoreactivity, 5-ethynyl-2'-deoxyuridine incorporation, and cell-cycle analysis of cells grown in low-Cl(-) media showed fewer proliferating cells than in cultures grown in regular medium. We confirmed that mice lacking Ano1 had less phosphorylated retinoblastoma protein compared with controls. These data led us to conclude that Ano1 regulates proliferation at the G(1)/S transition of the cell cycle and may play a role in tumorigenesis.
Asunto(s)
Canales de Cloruro/fisiología , Células Intersticiales de Cajal/citología , Células Intersticiales de Cajal/fisiología , Proteínas de Neoplasias/fisiología , Neoplasias Pancreáticas/patología , Ácido 4,4'-Diisotiocianostilbeno-2,2'-Disulfónico/farmacología , Animales , Animales Recién Nacidos , Anoctamina-1 , Antineoplásicos Hormonales/farmacología , División Celular/fisiología , Línea Celular Tumoral , Canales de Cloruro/antagonistas & inhibidores , Cloruros/metabolismo , Inhibidores de la Ciclooxigenasa/farmacología , Femenino , Neoplasias Gastrointestinales/patología , Neoplasias Gastrointestinales/fisiopatología , Tumores del Estroma Gastrointestinal/patología , Tumores del Estroma Gastrointestinal/fisiopatología , Humanos , Activación del Canal Iónico/efectos de los fármacos , Activación del Canal Iónico/fisiología , Antígeno Ki-67/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Proteínas de Neoplasias/antagonistas & inhibidores , Ácido Niflúmico/farmacología , Neoplasias Pancreáticas/fisiopatología , Cultivo Primario de Células , Proteína de Retinoblastoma/metabolismo , Tamoxifeno/farmacologíaAsunto(s)
Endoscopía del Sistema Digestivo , Neoplasias Gastrointestinales , Tumores del Estroma Gastrointestinal , Mesilato de Imatinib/administración & dosificación , Anciano de 80 o más Años , Antineoplásicos/administración & dosificación , Disección/métodos , Endoscopía del Sistema Digestivo/instrumentación , Endoscopía del Sistema Digestivo/métodos , Unión Esofagogástrica/diagnóstico por imagen , Unión Esofagogástrica/patología , Unión Esofagogástrica/cirugía , Femenino , Neoplasias Gastrointestinales/diagnóstico , Neoplasias Gastrointestinales/patología , Neoplasias Gastrointestinales/fisiopatología , Neoplasias Gastrointestinales/cirugía , Tumores del Estroma Gastrointestinal/diagnóstico , Tumores del Estroma Gastrointestinal/patología , Tumores del Estroma Gastrointestinal/fisiopatología , Tumores del Estroma Gastrointestinal/cirugía , Humanos , Laparoscopía/métodos , Terapia Neoadyuvante/métodos , Cirugía Asistida por Computador/instrumentación , Cirugía Asistida por Computador/métodos , Resultado del TratamientoRESUMEN
Familial gastrointestinal stromal tumor (GIST) is an extremely rare autosomal dominant disorder, and approximately 20 families have been reported to date. In this article, we present one additional family. A 25-year-old Japanese woman presented with abdominal pain, and subsequent image analyses disclosed multiple tumors measuring 12 cm in maximum diameter in the lower digestive tract. The postoperative histologic examination showed multiple GISTs and diffuse hyperplasia of interstitial cells of Cajal. Her mother had a history of GIST in the digestive tract. Three members of this family including her younger sister and mother had cutaneous hyperpigmentation of external genitalia and axilla. Their DNA samples showed identical missense mutation at exon 11 in the juxtamembrane domain of the KIT gene, and this mutation site was considered to be a hot spot in familial GIST. One year after, her younger sister suffered from multiple GISTs in the digestive tract at the age of 25 years. To correctly diagnose familial GIST, mutual information should be exchanged among clinicians, pathologists, and molecular scientists.
Asunto(s)
Exones/genética , Neoplasias Gastrointestinales/genética , Tumores del Estroma Gastrointestinal/genética , Mutación Missense , Proteínas Proto-Oncogénicas c-kit/genética , Adulto , Femenino , Neoplasias Gastrointestinales/patología , Neoplasias Gastrointestinales/fisiopatología , Tumores del Estroma Gastrointestinal/patología , Tumores del Estroma Gastrointestinal/fisiopatología , Mutación de Línea Germinal , Humanos , Hiperplasia , Células Intersticiales de Cajal/patologíaRESUMEN
Gastrointestinal stromal tumor (GIST) account for 1% of all gastrointestinal neoplasms and are the most common mesenchymal tumor of gastrointestinal tract. There are considered to originate fom the intestinal cell of Cajal, an intestinal pacemaker cell, characterized usually express the KIT protein on immunohistochemistry. The stomach (40-60%) and small intestine (30-40%) are the most common locations. Diagnosis of these tumors is difficult to establish, because symptoms are vague and traditional diagnostic tests are not specific. GISTs shows a wide variety of clinical behaviours ranging fom benign to frankly malignant, making the outcome totally unpredictable. Surgery is the standard treatment of local GIST while Imatinib (tyrosine kinasi inhibitor) is considered as the standard treatment of metastatic disease. Resistence to Imatinib is also becoming a major clinical problem but new tirosyne kinase inibitor are being studied to improve the treatment and survival. The present paper is a review of the salient features of epidemiology, pathophysiology, diagnosis, therapy and prognostic factors of GIST
Asunto(s)
Tumores del Estroma Gastrointestinal , Antineoplásicos/uso terapéutico , Benzamidas , Procedimientos Quirúrgicos del Sistema Digestivo , Progresión de la Enfermedad , Tumores del Estroma Gastrointestinal/diagnóstico , Tumores del Estroma Gastrointestinal/epidemiología , Tumores del Estroma Gastrointestinal/fisiopatología , Tumores del Estroma Gastrointestinal/terapia , Humanos , Mesilato de Imatinib , Indoles/uso terapéutico , Neoplasias Intestinales/diagnóstico , Neoplasias Intestinales/epidemiología , Neoplasias Intestinales/fisiopatología , Neoplasias Intestinales/terapia , Italia/epidemiología , Piperazinas/uso terapéutico , Pronóstico , Pirimidinas/uso terapéutico , Pirroles/uso terapéutico , Factores de Riesgo , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/epidemiología , Neoplasias Gástricas/fisiopatología , Neoplasias Gástricas/terapia , Sunitinib , Resultado del TratamientoRESUMEN
Gastrointestinal stromal tumour (GIST) is the most common mesenchymal neoplasm of the gastrointestinal tract. GISTs are believed to originate from intersticial cells of Cajal (the pacemaker cells of the gastrointestinal tract) or related stem cells, and are characterized by KIT or platelet-derived growth factor receptor alpha (PDGFRA) activating mutations. The use of imatinib has revolutionized the management of GIST and altered its natural history, substantially improving survival time and delaying disease progression in many patients. The success of imatinib in controlling advanced GIST led to interest in the neoadjuvant and adjuvant use of the drug. The neoadjuvant (preoperative) use of imatinib is recommended to facilitate resection and avoid mutilating surgery by decreasing tumour size, and adjuvant therapy is indicated for patients at high risk of recurrence. The molecular characterization (genotyping) of GISTs has become an essential part of the routine management of the disease as KIT and PDGFRA mutation status predicts the likelihood of achieving response to imatinib. However, the vast majority of patients who initially responded to imatinib will develop tumour progression (secondary resistance). Secondary resistance is often related to secondary KIT or PDGFRA mutations that interfere with drug binding. Multiple novel tyrosine kinase inhibitors may be potentially useful for the treatment of imatinib-resistant GISTs as they interfere with KIT and PDGFRA receptors or with the downstream-signalling proteins.
Asunto(s)
Antineoplásicos/uso terapéutico , Tumores del Estroma Gastrointestinal/tratamiento farmacológico , Piperazinas/uso terapéutico , Pirimidinas/uso terapéutico , Benzamidas , Progresión de la Enfermedad , Resistencia a Antineoplásicos/genética , Tumores del Estroma Gastrointestinal/genética , Tumores del Estroma Gastrointestinal/patología , Tumores del Estroma Gastrointestinal/fisiopatología , Humanos , Mesilato de Imatinib , Mutación , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-kit/genética , Proteínas Proto-Oncogénicas c-kit/metabolismo , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/genética , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/metabolismoRESUMEN
BACKGROUND & AIMS: Gastrointestinal stromal tumors (GISTs) express the receptor tyrosine kinase c-kit. Approximately 90% of GISTs have gain-of-function mutations in the Kit gene, which leads to its constitutive activation and drives malignant behavior of GISTs. Interstitial cells of Cajal (ICC) express c-kit; however, it is unknown whether uncontrolled hyperplasia of ICC is responsible for GISTs. Here, we sought to determine whether gain-of-function mutations in Kit lead to hyperplasia of all classes of ICC, whether ICC hyperplasia begins before birth, and whether functional defects occur in ICC hyperplasia or the development of GISTs. METHODS: Heterozygous mutant Kit(V558Delta)/+ mice that develop symptoms of human familial GISTs and prematurely die from pathology of the gastrointestinal tract were utilized and compared with wild-type controls. C-kit-immunohistochemistry and intracellular electrical recording of spontaneous and nerve-evoked activity were applied to examine the density and functionality of ICC in these mutants. RESULTS: There was considerable hyperplasia in all classes of ICC throughout the GI tract of Kit(V558Delta)/+ mice, except for ICC in the deep muscular plexus of the intestine. Spontaneous electrical activity and postjunctional neural responses in hyperplastic ICC tissues appeared normal but were up-regulated in the cecum, where GISTs were commonly found. CONCLUSIONS: Kit gain-of-function leads to hyperplasia of most classes of ICC throughout the GI tract. ICC retain normal pacemaker function and enteric neural responses well after development of hyperplasia.
Asunto(s)
Tumores del Estroma Gastrointestinal/patología , Tumores del Estroma Gastrointestinal/fisiopatología , Tracto Gastrointestinal/patología , Tracto Gastrointestinal/fisiopatología , Músculo Liso/patología , Músculo Liso/fisiopatología , Animales , Ciego/metabolismo , Ciego/patología , Ciego/fisiopatología , Colon/metabolismo , Colon/patología , Colon/fisiopatología , Modelos Animales de Enfermedad , Fenómenos Electrofisiológicos , Sistema Nervioso Entérico/fisiopatología , Feto/metabolismo , Feto/patología , Feto/fisiopatología , Fundus Gástrico/metabolismo , Fundus Gástrico/patología , Fundus Gástrico/fisiopatología , Tumores del Estroma Gastrointestinal/metabolismo , Tracto Gastrointestinal/metabolismo , Hiperplasia/metabolismo , Hiperplasia/patología , Hiperplasia/fisiopatología , Íleon/metabolismo , Íleon/patología , Íleon/fisiopatología , Yeyuno/metabolismo , Yeyuno/patología , Yeyuno/fisiopatología , Masculino , Ratones , Ratones Mutantes , Músculo Liso/metabolismo , Proteínas Proto-Oncogénicas c-kit/genética , Proteínas Proto-Oncogénicas c-kit/metabolismo , Antro Pilórico/metabolismo , Antro Pilórico/patología , Antro Pilórico/fisiopatologíaRESUMEN
Recent years have seen a growing interest in insulin-like growth factor 1 receptor (IGF1R) in medical oncology. Interesting data have been reported also on IGF1r in gastrointestinal stromal tumors (GISTs) especially in children and in young adult patients whose disease does not harbour mutations on KIT and PDGFRA and are poorly responsive to conventional therapies. However, it is too early to reach conclusions on IGF1R as a novel therapeutic target in GIST because the receptor's biological role is still to be defined and the clinical significance in patients needs to be studied in larger studies. We update and comment the current literature on IGF1R in GISTs and discuss the future perspectives in this promising field.
Asunto(s)
Tumores del Estroma Gastrointestinal/fisiopatología , Receptor IGF Tipo 1/fisiología , Humanos , Mutación , Receptor IGF Tipo 1/genéticaRESUMEN
OBJECTIVE: The clinical course of gastrointestinal stromal tumor (GIST) spans a wide spectrum from a curable disorder to a highly malignant disease that leads to metastasis and death. To develop prognostic modalities for GIST patients, we developed a mouse monoclonal antibody against pfetin, the prognostic value of which has been previously reported. METHODS: The reactivity of the monoclonal antibody against pfetin was examined by western blotting and immunohistochemistry. RESULTS: Western blotting demonstrated that the monoclonal antibody was specific to pfetin. The immunohistochemical study demonstrated that the 5-year disease-free survival rate was 93.2% and 94.5% for GIST patients with pfetin-positive tumors and 70.0% and 80.7% for those with pfetin-negative tumors in the 159 cases from the National Cancer Center Hospital (P < 0.0001) and in the 100 cases from Niigata University Medical and Dental Hospital (P < 0.0001), respectively. Uni- and multivariate analyses revealed that pfetin expression was a powerful prognostic factor among the clinico-pathological parameters examined. CONCLUSIONS: These results establish pfetin as a practical prognostic marker for GIST patients after surgery. Pfetin may also present a novel therapeutic target to prevent recurrence of GIST.
Asunto(s)
Anticuerpos Monoclonales , Biomarcadores de Tumor/sangre , Tumores del Estroma Gastrointestinal/diagnóstico , Proteínas/análisis , Adulto , Anciano , Anciano de 80 o más Años , Animales , Biomarcadores de Tumor/química , Biomarcadores de Tumor/inmunología , Western Blotting , Línea Celular Tumoral , Electroforesis en Gel de Poliacrilamida , Femenino , Tumores del Estroma Gastrointestinal/inmunología , Tumores del Estroma Gastrointestinal/fisiopatología , Humanos , Inmunohistoquímica , Masculino , Ratones , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Proteínas/química , Proteínas/genéticaRESUMEN
To identify significant clinical and CT features for the differentiation of gastrointestinal stromal tumors (GISTs) from leiomyomas in the esophagogastric junction (EGJ).One hundred thirty six patients with pathologically proven GISTs (nâ=â87) and leiomyomas (nâ=â49) in the EGJ were enrolled. And preoperative CT images were available in 73 GISTs cases and 34 leiomyoma cases. Two radiologists reviewed the CT images by consensus with regard to tumor size, shape, growth pattern, surface, enhancement pattern, enhancement degree, attention at each phasic image and the presence of surface ulcer, calcification, and intralesional low attention.Eight significant clinical and CT features were identified for differentiating GISTs from leiomyomas: older age (>46.5 years), tumor long diameter >4.5âcm, heterogeneous enhancement, high degree enhancement, mean CT attenuation >69.2 HU, presences of intralesional low attenuation and surface ulcer, absences of calcification (Pâ<â.05). On the receiver operating characteristic curve analysis, an optimal cutoff score of 3.5 was achieved for differentiating GISTs from leiomyomas with an AUC of 0.844 (sensitivity: 76.7%, specificity: 76.5%).older age (>46.5 years), tumor long diameter >4.5âcm, heterogeneous enhancement, high degree enhancement, mean CT attenuation >69.2 HU, presences of intralesional low attenuation and surface ulcer, absence of calcification are significant features highly suggestive of GISTs in differentiation from leiomyomas in the EGJ.
Asunto(s)
Tumores del Estroma Gastrointestinal/etiología , Leiomioma/complicaciones , Adulto , Anciano , Análisis de Varianza , China , Femenino , Tumores del Estroma Gastrointestinal/fisiopatología , Humanos , Leiomioma/fisiopatología , Masculino , Persona de Mediana Edad , Curva ROC , Tomografía Computarizada por Rayos X/métodosRESUMEN
RATIONALE: Available literature states that the histological subtype of the gastrointestinal stromal tumor (GIST) with pulmonary metastasis is often spindle cell type. To our knowledge, this is the first report of the GIST with pulmonary metastasis of very uncommon epithelioid subtype. PATIENT CONCERNS: We report a 63-year-old male presenting with the symptom of bloodstained sputum without obvious inducement. The patient had no chest pain, low back pain, fatigue, fever or night sweats symptoms. DIAGNOSES: Combined chest digital radiography and the history of the patient who presented with the colon GIST of the epithelioid subtype two years ago that the mass may be a metastasis tumor. Combined with morphological and immunohistochemical staining results, a pathological diagnosis of the GIST with pulmonary metastasis was considered. INTERVENTIONS: Right lobectomy and partial upper lobectomy were performed. OUTCOMES: The patient had not experienced any noticeable symptom and recurrent tumors at 6 months follow-up. LESSONS: We report a rare case of the GIST with pulmonary metastasis of epithelioid subtype. This case is of great significance to the pathologist's clinical work. For pathologists, if an epithelioid tumor in the lung is found, it is necessary to check whether the gastrointestinal tract also has the tumor, which may be an epithelioid GIST with pulmonary metastasis.
Asunto(s)
Tumores del Estroma Gastrointestinal/complicaciones , Neoplasias Pulmonares/etiología , Biomarcadores de Tumor/análisis , Tumores del Estroma Gastrointestinal/patología , Tumores del Estroma Gastrointestinal/fisiopatología , Humanos , Pulmón/anomalías , Pulmón/patología , Neoplasias Pulmonares/fisiopatología , Neoplasias Pulmonares/cirugía , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia/patología , Metástasis de la Neoplasia/fisiopatologíaRESUMEN
A 32 years old gentleman presented with a lump occupying the epigastric, left hypochondriac and umbilical region for the last 3 months which gradually increased in size & dull aching pain. He also complained of low grade fever and early satiety. On examination, he had a lump on upper abdomen which was irregular, firm, mildly tender, lobulated surface, restricted mobility, dull on percussion. USG examination of HBS revealed hepatomegaly and SOL in liver. CT abdomen revealed soft tissue mass in left upper abdomen. FNA revealed cells of mesenchymal origin. Per operatively a large lobulated, myxomatous highly vascular mass arising from the fundal part of the stomach was found and removed. Histopathology report comments about two differential diagnosis-leiomyosarcoma and gastrointestinal stromal tumour. CD117 immunostaining confirmed it was gastrointestinal stromal tumor (GIST). Post operatively patient was treated by Imatinib and is now under regular follow up.
Asunto(s)
Antineoplásicos/uso terapéutico , Tumores del Estroma Gastrointestinal/diagnóstico , Piperazinas/uso terapéutico , Pirimidinas/uso terapéutico , Adulto , Benzamidas , Biopsia con Aguja Fina , Diagnóstico Diferencial , Fundus Gástrico/patología , Fundus Gástrico/cirugía , Tumores del Estroma Gastrointestinal/tratamiento farmacológico , Tumores del Estroma Gastrointestinal/fisiopatología , Tumores del Estroma Gastrointestinal/cirugía , Humanos , Mesilato de Imatinib , MasculinoAsunto(s)
Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Duodeno/patología , Neoplasias Gastrointestinales , Tumores del Estroma Gastrointestinal , Intestino Delgado/patología , Adulto , Femenino , Neoplasias Gastrointestinales/diagnóstico , Neoplasias Gastrointestinales/fisiopatología , Neoplasias Gastrointestinales/cirugía , Tumores del Estroma Gastrointestinal/diagnóstico , Tumores del Estroma Gastrointestinal/fisiopatología , Tumores del Estroma Gastrointestinal/cirugía , Humanos , Cuidados Intraoperatorios/métodos , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
Mesenchymal tumors of the gallbladder are rarely encountered in clinical practice. The Gastrointestinal Stromal Tumor (GIST) of the gallbladder is rarely encountered. These tumors most commonly arise from the interstitial cells of Cajal (ICC), the pacemakers of the intestinal system. There can be benign as well as malignant forms of GIST. The literature on GIST arising from the gallbladder wall is limited to a few case reports only. In extensive search of the indexed literature, only 9 cases of gallbladder GIST were retrieved. Based on the available literature these tumors are commonly found in females. They usually present with hypochondrial pain with or without other features of cholangitis. These tumors are usually malignant and warrant a radical surgical excision. The data on postoperative adjuvant therapy and survival is limited. The authors presented a review of the available literature on this rare pathology.
Asunto(s)
Vesícula Biliar/fisiopatología , Vesícula Biliar/cirugía , Tumores del Estroma Gastrointestinal/diagnóstico , Tumores del Estroma Gastrointestinal/fisiopatología , Tumores del Estroma Gastrointestinal/cirugía , Células Intersticiales de Cajal/patología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores SexualesRESUMEN
An unconscious 55-year-old man with a history of neurofibromatosis type 1 (NF1) was transported to the emergency department and was diagnosed with acute renal failure owing to a large bladder tumor. A submucosal tumor was also identified in the duodenum. The patient was diagnosed with a primary gastrointestinal stromal tumor (GIST) of the bladder and duodenum. After six cycles of regorafenib therapy, 18F-fluorodeoxyglucose accumulation in the duodenal GIST on positron emission tomography-computed tomography (PET-CT) showed a partial metabolic response. Currently, no standard drug therapy for unresectable or relapsed NF1-associated GIST has been established. Regorafenib may thus be considered as and appropriate initial therapy.
Asunto(s)
Duodeno/patología , Inhibidores Enzimáticos/uso terapéutico , Tumores del Estroma Gastrointestinal/tratamiento farmacológico , Tumores del Estroma Gastrointestinal/patología , Neurofibromatosis 1/patología , Compuestos de Fenilurea/uso terapéutico , Piridinas/uso terapéutico , Neoplasias de la Vejiga Urinaria/patología , Tumores del Estroma Gastrointestinal/diagnóstico por imagen , Tumores del Estroma Gastrointestinal/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Neurofibromatosis 1/diagnóstico por imagen , Neurofibromatosis 1/etiología , Tomografía Computarizada por Tomografía de Emisión de Positrones , Resultado del TratamientoRESUMEN
BACKGROUND/AIM: DOG1 is a calcium-activated chloride channel that has gained attention as a promising drug target due to its involvement in several processes essential for tumor development and progression. DOG1 is overexpressed in >95% of gastrointestinal stromal tumors (GIST). The aim was to determine DOG1 inhibition antitumoral effects on GIST. MATERIALS AND METHODS: Human GIST (GIST-T1 and GIST882) cell lines were used to study the effect of DOG1 inhibitors on chloride currents, viability, colony formation, and cell cycle. RESULTS: CaCCinh-A01 decreased chloride currents. CaCCinh-A01 and T16inh-A01 reduced GIST cell viability and CaCCinh-A01 affected cell cycle distribution leading to G1 cell-cycle arrest. CaCCinh-A01 also increased the sub-G1 phase population, indicative of apoptosis, in GIST882. CaCCinh-A01 strongly reduced the colony forming ability of the cells, whereas T16inh-A01 did not. CONCLUSION: DOG1 inhibition has antitumoral effects in GIST cells in vitro, and could potentially serve as a target for GIST therapy.
Asunto(s)
Anoctamina-1/antagonistas & inhibidores , Neoplasias Gastrointestinales/tratamiento farmacológico , Tumores del Estroma Gastrointestinal/tratamiento farmacológico , Proteínas de Neoplasias/antagonistas & inhibidores , Anoctamina-1/fisiología , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Neoplasias Gastrointestinales/fisiopatología , Tumores del Estroma Gastrointestinal/fisiopatología , Humanos , Proteínas de Neoplasias/fisiología , Pirimidinas/farmacología , Tiazoles/farmacología , Tiofenos/farmacologíaRESUMEN
RATIONALE: Small intestine stromal tumors (SISTs) are a type of gastrointestinal stromal tumor (GIST) that has an insidious onset. Natural orifice specimen extraction (NOSE) surgery has been gradually developed for the treatment of colorectal, stomach, small intestine, hepatobiliary, and gynecological tumors because of its safety and feasibility. This case study explored the possibility of applying the NOSE method for the treatment of SIST. PATIENT CONCERNS: A 59-year-old male patient was admitted to the hospital after having an irregular abdominal mass for >1 month that was detected by a medical examination. Thoracic and abdominopelvic enhanced computer tomography revealed irregular masses on the left side of the abdominal cavity. DIAGNOSIS: Sist. INTERVENTIONS: Nose (laparoscopic resection of intestinal stromal tumors with transrectal extract specimen and no abdominal auxiliary incision) surgery was performed. OUTCOMES: The patient underwent operation successfully and recuperates well with no complications. LESSONS: Nose surgery is minimally invasive, results in patient recuperation with no complications, and is considered to be feasible for SIST treatment.
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Colectomía/métodos , Tumores del Estroma Gastrointestinal , Neoplasias Intestinales , Laparoscopía/métodos , Cirugía Endoscópica por Orificios Naturales/métodos , Tumores del Estroma Gastrointestinal/patología , Tumores del Estroma Gastrointestinal/fisiopatología , Tumores del Estroma Gastrointestinal/cirugía , Humanos , Neoplasias Intestinales/patología , Neoplasias Intestinales/fisiopatología , Neoplasias Intestinales/cirugía , Intestinos/diagnóstico por imagen , Intestinos/patología , Intestinos/cirugía , Masculino , Persona de Mediana Edad , Tempo Operativo , Tomografía Computarizada por Rayos X/métodos , Resultado del TratamientoRESUMEN
Sunitinib is approved for the treatment of metastatic renal cell carcinoma (RCC) and imatinib-resistant or -intolerant gastrointestinal stromal tumours (GIST). Several studies have identified unexpected rates of thyroid dysfunction with sunitinib treatment. We performed a prospective observational study with the aim of more accurately defining the incidence and severity of hypothyroidism in RCC or GIST patients receiving sunitinib. Thyroid function was assessed at baseline and on days 1 and 28 of each treatment cycle. Thyroid antibodies were assessed at baseline and during follow-up if abnormal thyroid function tests were recorded. Sixteen patients (27%) developed sub- or clinical hypothyroidism and required hormone replacement and 20 patients (34%) showed at least one elevated thyroid-stimulating hormone not requiring therapeutic intervention. Twenty patients (34%) did not develop any biochemical thyroid abnormality. Thus, sunitinib can induce (sub-) clinical hypothyroidism, warranting close monitoring of thyroid function. We propose a new algorithm for managing this side effect in clinical practise.