Tumor de GIST, presentación no habitual / GIST tumor: an unusual presentation

RESUMEN El tumor estromal gastrointestinal representa el 3% de las neoplasias gastrointestinales; es el tumor mesenquimático más frecuente. Afecta a hombres mayores de 50 años. El 80% son benignos, la mayoría afectan el estómago e intestino delgado. La incidencia de localización extragastrointestinal es desconocida. Paciente masculino de 56 años, tabaquista, obeso, con hipertensión arterial (HTA) y diabético (DBT), anticoagulado, consulta por dolor en fosa ilíaca derecha, posterior a esfuerzo físico. Se realiza tomografía computarizada (TC) donde se visualiza lesión de aspecto expansivo intraperitoneal que muestra realce periférico. Se decide conducta quirúrgica. Se halla un tumor mesentérico. En su presentación, estos tumores hasta en un 60% suelen ser asintomáticos por lo que resultan solo un hallazgo imagenológico; es indispensable, pues, su sospecha clínica y fundamentalmente el aporte de la inmunohistoquímica para la definición de la patología. El CD 117 es el principal marcador. Su tratamiento de preferencia es siempre quirúrgico, acompañado de tratamientos quimioterápicos.

ABSTRACT Gastrointestinal stromal tumors (GISTs) account for < 3% of gastrointestinal neoplasms and are the most common mesenchymal tumors. They are more common in men > 50 years. They are benign in 80% of the cases and usually occur in the stomach and small intestine. The incidence of extragastrointestinal GISTs is unknown. A 56-year-old male patient sought medical care for abdominal pain in the right iliac fossa that appeared after exercising. The patient was a current smoker, obese, had a history of hypertension (HTN) and diabetes (DBT) and was receiving anticoagulants. A computed tomography (CT) scan showed an expansive mass within the peritoneum with peripheral enhancement. Surgical management was decided. During the procedure, a tumor was found in the mesentery. Up to 60% of these tumors are usually asymptomatic and are incidentally found in imaging tests; therefore, clinical suspicion and, most importantly immunohistochemistry, are essential for the diagnosis. CD117 is the main marker. Surgery is the treatment of choice for GISTs and chemotherapy is also indicated.

GIST gástrico complicado. Una forma de presentación inusual / Complicated gastric GIST. An unusual presentation

RESUMEN Los tumores GIST son un motivo de consulta cada vez más frecuente en las entrevistas de cirugía gastroenterológica. Suelen ser derivados como hallazgos incidentales o por presentar síntomas derivados de su crecimiento. Se presenta el caso clínico de una paciente que requirió internación de urgencia por síndrome anémico agudo. Se comenta su algoritmo diagnóstico y su resolución quirúrgica. Asimismo se comentan los estándares de diagnóstico y tratamiento actuales con especial foco en la estrategia quirúrgica, la cual debe ser individualizada según cada caso.

ABSTRACT Gastrointestinal stromal tumors (GISTs) are becoming an increasingly common reason for consultation in gastroenterology surgery interviews. Patients are usually referred for surgery due to an incidental finding or symptoms associated with tumor growth. We report the case of a female patient who required urgent hospitalization due to acute anemic syndrome. The diagnostic algorithm and surgical approach are described. The current standards of diagnosis and treatment are also discussed, with special focus on the surgical strategy, which must be tailored to each case.

Prognostic factors and management of colorectal gastrointestinal stromal tumors

Introduction: The gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm of the gastrointestinal tract. Even though it can be found in any location of the digestive tract, the colorectal GIST is rare. With this study, we aim to review the current knowledge regarding the prognosis and management of colorectal GIST. Methods: A literature search was conducted in PubMed, and 717 articles were collected. After analyzing these studies, 60 articles were selected to use in this review. Results: The mitotic index, as well as tumor size and location were identified as good discriminators of prognosis in various studies. Surgery remains the only curative therapy for potentially resectable tumors. However, even after surgical resection, some patients develop disease recurrence and metastasis, especially those with highrisk tumors. Therefore, surgical resection alone might be inadequate for the management of all colorectal GISTs. The discovery of GIST's molecular pathway led to a shift in its therapy, insofar as tyrosine kinase inhibitors became part of the treatment schemes for this tumor, revolutionizing the treatment's outcome and prognosis. Discussion/Conclusion: The controversy concerning colorectal GIST prognosis and treatment can be, in part, attributed to the limited number of studies in the literature. In this review, we gathered the most recent knowledge about the prognosis and management of GIST in this rare location and propose two algorithms for its approach. Lastly, we highlight the importance of an individualized approach in the setting of a multidisciplinary team. (AU)

Performance of the Combined Model Based on Both Clinicopathological and CT Texture Features in Predicting Liver Metastasis of High-risk Gastrointestinal Stromal Tumors / 中国医学科学院学报

Objective To investigate the performance of the combined model based on both clinicopathological features and CT texture features in predicting liver metastasis of high-risk gastrointestinal stromal tumors(GISTs). Methods The high-risk GISTs confirmed by pathology from January 2015 to December 2020 were analyzed retrospectively,including 153 cases from the Cancer Hospital of the University of Chinese Academy of Sciences and 51 cases from the Shaoxing Central Hospital.The cases were randomly assigned into a training set(n=142)and a test set(n=62)at a ratio of 7∶3.According to the results of operation or puncture,they were classified into a liver metastasis group(76 cases)and a non-metastasis group(128 cases).ITK-SNAP was employed to delineate the volume of interest of the stromal tumors.Least absolute shrinkage and selection operator(LASSO)was employed to screen out the effective features.Multivariate logistic regression was adopted to construct the models based on clinicopathological features,texture features extracted from CT scans,and the both(combined model),respectively.Receiver operating characteristic(ROC)curve and calibration curve were established to evaluate the predictive performance of the models.The area under the curve(AUC)was compared by Delong test. Results Body mass index(BMI),tumor size,Ki-67,tumor occurrence site,abdominal mass,gastrointestinal bleeding,and CA125 level showed statistical differences between groups(all P<0.05).A total of 107 texture features were extracted from CT images,from which 13 and 7 texture features were selected by LASSO from CT plain scans and CT enhanced scans,respectively.The AUC of the prediction with the training set and the test set respectively was 0.870 and 0.855 for the model based on clinicopathological features,0.918 and 0.836 for the model based on texture features extracted from CT plain scans,0.920 and 0.846 for the model based on texture features extracted from CT enhanced scans,and 0.930 and 0.889 for the combined model based on both clinicopathological features and texture features extracted from CT plain scans.Delong test demonstrated no significant difference in AUC between the models based on the texture features extracted from CT plain scans and CT enhanced scans(P=0.762),whereas the AUC of the combined model was significantly different from that of the clinicopathological feature-based model and texture feature-based model(P=0.001 and P=0.023,respectively). Conclusion Texture features extracted from CT plain scans can predict the liver metastasis of high-risk GISTs,and the model established with clinicopathological features combined with CT texture features has best prediction performance.

Gist gigante de alto riesgo: Reporte de caso y revisión de la literatura / Giant GIST of High-risk Criteria: Case Report and Literature Review

RESUMEN Los tumores del estroma gastrointestinal (GIST) son las neoplasias mesenquimales más frecuentes del tracto digestivo. Los criterios de estadificación del riesgo, como angioinvasion, tamaño, infiltración y el índice mitótico, permiten realizar un adecuado diagnóstico y tratamiento. Se presenta un paciente masculino de 67 años de edad, quien consultó por he-matemesis y melenas. Endoscópicamente se observó una masa en el estómago de 20x10x6 cm de diámetro de la cual se tomó biopsia para estudio. Al examen histopatológico se diagnósticó un GIST con invasión microscópica de la lámina propia y angioinvasión, estos dos componentes histopatológicos son escasamente tomados en cuenta para clasificar GIST; sin embargo, son muy importantes en este contexto, pues cambian el pronóstico de la enfermedad y con requerimiento de terapia adyuvante con imatinib. El desenlace del paciente fue favorable, debido a la conducta terapéutica establecida. El comportamiento biológico del GIST varía dependiendo de las características clínicas e histopatológicas. Este caso resalta los criterios de alto riesgo del GIST y la necesidad de modificar el tratamiento cuando están presentes.

ABSTRACT Gastrointestinal stromal tumors (GIST) are the most common mesenchymal neoplasms of the digestive tract. Risk staging criteria such as angioinvasion, size, infiltration, and mitotic index allow for adequate diagnosis and treatment. A 67-year-old male patient is presented, who consulted for hematemesis and melena. Endoscopically, a 20x10x6 cm diameter mass was observed in the stomach, which was taken for a biopsy for study. On histopathological examination, a GIST with the microscopic invasion of the lamina propia and angioinvasion was diagnosed. These two histopathological components are scarcely taken into account to classify GIST; however, they are very important in this context, changing the prognosis of the disease and requiring adjuvant therapy with imatinib. The outcome of the patient was favorable due to the established therapeutic conduct. The biological behavior of GIST varies depending on the clinical and histopathological characteristics. This case highlights the high-risk criteria for GIST and the need to modify the treatment when present.

Tumores del estroma gastrointestinal en un Hospital de México / Gastrointestinal stroma tumor in a hospital of Mexico

Introducción: Los tumores del estroma gastrointestinal son neoplasias de comportamiento benigno o maligno. Se originan de las células intersticiales de Cajal del tubo digestivo. Objetivo: Describir dos formas distintas de presentación clínica de los tumores del estroma gastrointestinal. Casos clínicos: El caso 1, paciente femenina de 65 años de edad que acudió por síntomas compresivos del tubo digestivo superior a causa de un gastrointestinal gástrico. El caso 2, paciente masculino de 56 años de edad que acudió por sangrado de tubo digestivo medio ocasionado por un gastrointestinal intestinal. Conclusiones: Los tumores del estroma gastrointestinal tienen distinta presentación clínica. Su tratamiento es esencialmente quirúrgico y en algunos casos complementados con terapia molecular dirigida(AU)

Introduction: Gastrointestinal stromal tumors are neoplasms of benign or malignant behavior. They originate from the interstitial cells of Cajal in the digestive tract. Objective: The objective of this work is to describe two different forms of clinical presentation. Case report: case 1: 65-year-old female patient who presented for compression symptoms of the upper digestive tract due to gastric GIST; case 2: 56-year-old male who presented with bleeding from the middle digestive tract caused by intestinal GIST. Conclusions: GISTs have different clinical presentation. Its treatment is essentially surgical and in some cases supplemented with targeted molecular therapy(AU)

Tumor de estroma gastrointestinal extraintestinal gigante: reporte de un caso y revisión de bibliografía / Giant extraintestinal gastrointestinal stromal tumor: Case report and bibliography review

Resumen Los tumores del estroma gastrointestinal (GIST) son tumores infrecuentes del tracto digestivo. Sus localizaciones más frecuentes son el estómago, intestino delgado, colon y recto; su aparición en otros lugares fuera del trato gastrointestinal como el mesenterio, epiplón o retroperitoneo es infrecuente. La tomografía axial computarizada (TAC) y la resonancia magnética (RM) son los estudios de imágenes de primera elección. La recesión quirúrgica es el estándar de oro para los tumores localizados y en los tumores avanzados o metastásicos son tratados con imatinib. A continuación, se presenta el caso de un paciente masculino de 53 años de edad sin antecedentes de patologías previos con cuadro clínico de dolor abdominal generalizado, pérdida de peso de 20 kg aproximadamente, distención abdominal, melena, hematemesis y astenia; en el examen físico presentó abdomen distendido y en la palpación se encontró endurecimiento epigástrico y mesogástrico, y marco colónico izquierdo. En la tomografía de abdomen se observó una masa tumoral de aspecto infiltrativo de aparente origen gástrico, con crecimiento extragástrico e infiltración del bazo, páncreas, raíz mesentérica, epiplón mayor, colon transverso, asas intestinales delgadas e infiltración en el hilio hepático, y metástasis hepática. Además, el cuadro se asoció con enfermedad respiratoria por coronavirus del síndrome respiratorio agudo grave de tipo 2 (SARS-CoV-2; neumonía por coronavirus de 2019 [COVID-19]). Se realizó una biopsia percutánea ecodirigida en el hipocondrio izquierdo y la histología reportó un GIST. En este artículo se revisa la clínica, diagnóstico y tratamiento del GIST gigante extradigestivo.

Abstract Giant extraintestinal gastrointestinal stromal tumors (GIST) are rare tumors of the digestive tract. Its most frequent locations are the stomach, small intestine, colon, and rectum. Its appearance in other places outside the gastrointestinal tract such as the mesentery, omentum, or retroperitoneum is infrequent. Computerized axial tomography (CT) and magnetic resonance imaging (MRI) are the imaging studies of the first choice. Surgical recession is the gold standard for localized tumors and advanced or metastatic tumors are treated with imatinib. This study presents the case of a male patient of 53 years with no history of previous pathologies. The patient was admitted with a clinical condition of generalized abdominal pain, weight loss of approximately 20 kg, abdominal distention, melena, hematemesis, and asthenia. Physical examination revealed a distended abdomen and palpation revealed epigastric and mesogastric hardening and left colonic frame. The abdominal tomography revealed a tumor mass with an infiltrative appearance of apparent gastric origin, with extragastric growth and infiltration of the spleen, pancreas, mesenteric root, greater omentum, transverse colon, thin intestinal loops, and infiltration in the hepatic hilum, and liver metastases. Moreover, the condition was related to the severe acute respiratory syndrome type 2 coronavirus (SARS-CoV-2). An ultrasound-guided percutaneous biopsy was performed in the left upper quadrant and histology reported a GIST. In this article medical condition, diagnosis, and treatment of the Giant extraintestinal gastrointestinal stromal, is reviewed.

Tumores estromales gastrointestinales (GIST) gástricos, serie de casos / Gastrointestinal stromal tumors (GIST). Case series

Resumen Introducción: Los tumores estromales gastrointestinales (GIST) representan hasta el 2 % de las neoplasias gastrointestinales, estos aparecen en cualquier parte del tracto gastrointestinal y son encontrados más frecuentemente en el estómago (60 %). El diagnóstico se realiza por la expresión de un receptor de factor de crecimiento de tirosina-cinasa, antígeno de diferenciación (CD) 117, lo que lo diferencia de los otros tumores mesenquimales como leiomiomas, leiomiosarcomas, leiomioblastomas y tumores neurogénicos, que no expresan esta proteína. Objetivo: El objetivo de nuestro trabajo es caracterizar los GIST de localización gástrica con respecto a su presentación clínica, diagnóstico, manejo, recurrencia y supervivencia. Métodos: Se trata de un estudio observacional, retrospectivo basado en una serie de casos. Se realizó una extracción de la información por medio de la revisión de las historias clínicas de los pacientes con GIST gástricos en un centro oncológico de Bogotá entre enero de 2005 y diciembre de 2015. La información recolectada incluyó tipo de manejo y abordaje quirúrgico, localización, tamaño, índice mitótico y clasificación de riesgo. Resultados: Se encontraron 31 pacientes con diagnóstico de GIST gástrico. La edad media fue de 62,3 años, con una mediana de 61 años. De los 31 pacientes, 18 fueron mujeres y 13 hombres. El tiempo de seguimiento estuvo entre un mínimo de 2,4 meses y un máximo de 214 meses, La mediana de seguimiento fue de 36 meses. Conclusiones: Los GIST son tumores potencialmente malignos, y el de localización gástrica es el más frecuente. El diagnóstico y tratamiento dependen de su tamaño y localización dentro del estómago. El manejo es variado y consiste en la resección quirúrgica, en la que los procedimientos son mínimamente invasivos, en combinación con la endoscopia, que son una buena alternativa al tratamiento abierto hasta que haya necesidad de terapia sistémica.

Abstract Introduction: Gastrointestinal stromal tumors (GIST) account for up to 2% of gastrointestinal neoplasms. They may appear anywhere in the gastrointestinal tract and are most frequently found in the stomach (60%). The diagnosis is made based on the expression of the tyrosine-protein kinase KIT CD117, which differentiates it from other mesenchymal tumors such as leiomyomas, leiomyosarcomas, leiomyoblastomas, and neurogenic tumors, that do not express this protein. Objective: To characterize the clinical presentation, diagnosis, treatment, recurrence, and survival of GISTs in the stomach. Materials and methods: This is an observational retrospective study based on a case series. Data was collected after reviewing the medical records of patients diagnosed with GIST at a cancer center in Bogotá between January 2005 and December 2015. The data included type of treatment and surgical approach, location, size, mitotic index, and risk classification. Results: There were 31 patients diagnosed with GIST. Their mean age was 62.3 years, with a median of 61 years. Of the 31 patients, 18 were women and 13 were men. Follow-up time ranged from a minimum of 2.4 months to a maximum of 214 months. The median follow-up time was 36 months. Conclusions: GISTs are potentially malignant tumors, with gastric location being the most frequent. Diagnosis and treatment depend on their size and location in the stomach. Treatment options vary, ranging from surgical resection, where minimally invasive procedures along with endoscopy are a suitable alternative to open surgery, to the need for systemic therapy.

Tumor del estroma gastrointestinal / Gastrointestinal stromal tumor

Introducción: El tumor del estroma gastrointestinal, es el tumor mesenquimal más frecuente en el tracto digestivo, que causa sangrado y obstrucción, con una incidencia de 10 a 20 casos por millón de habitantes. La prevalencia es mayor, debido el curso clínico largo de la enfermedad. Objetivo: Presentar un caso inusual de cirugía electiva, con tumor del estroma gastrointestinal digestivo, operado en el servicio de cirugía general. Caso clínico: Paciente masculino de 57 años de edad, que consulta por dolor abdominal en mesogastrio, acompañado de vómitos postprandiales tardíos, pérdida de peso y episodios recurrentes de sangrado digestivo bicolor, se ingresa de forma electiva y se estudia. Se interviene quirúrgicamente con el diagnóstico presuntivo de tumor abdominal. Se encuentra durante la laparotomía tumor de 14 por 20 centímetros que compromete la luz del intestino delgado, se decide realizar extracción del tumor y anastomosis término terminal convencional. El paciente fue egresado a los ocho días con evolución favorable y pendiente de resultado anatomopatológico, el cual informó tumor del estroma gastrointestinal. Conclusiones: Los tumores del estroma gastrointestinal son poco frecuentes como causa de cirugía electiva en los servicios de cirugía general(AU)

Introduction: Gastrointestinal stromal tumor is the most frequent mesenchymal tumor in the digestive tract, causing bleeding and obstruction, with an incidence of 10 to 20 cases per million inhabitants. The prevalence is higher, due to the long clinical course of the disease. Objective: To present an unusual case of elective surgery, with a gastrointestinal digestive stromal tumor, operated on in the general surgery service. Clinical case: A 57-year-old male patient who consulted for abdominal pain in the mesogastrium, accompanied by late postprandial vomiting, weight loss and recurrent episodes of bicolor digestive bleeding, was admitted electively and studied. Surgery was performed with the presumptive diagnosis of abdominal tumor. During the laparotomy, a 14 by 20-centimeter tumor that compromises the lumen of the small intestine is found; it is decided to perform extraction of the tumor and a conventional end-to-end anastomosis. The patient was discharged after eight days with a favorable evolution and pending histopathological result, which reported a gastrointestinal stromal tumor. Conclusions: Gastrointestinal stromal tumors are rare as a cause of elective surgery in general surgery services(AU)

Hemorragia de vías digestivas altas por presentación atípica de adenocarcinoma endometrial metastásico en el estómago. Tipificación diagnóstica con recursos endoscópicos / Upper gastrointestinal bleeding due to atypical presentation of metastatic endometrial adenocarcinoma in the stomach. Diagnostic typing with endoscopic resources

Resumen El cáncer de endometrio es la neoplasia ginecológica maligna más frecuente en el sexo femenino. Su presentación metastásica se limita principalmente a los órganos vecinos y ganglios cercanos, y es infrecuente la invasión al tubo digestivo superior. En el presente artículo se presenta una paciente que ingresó al servicio de urgencias con cuadro de hemorragia de vías digestivas altas, enfocado inicialmente como un tumor estromal gastrointestinal (GIST) de la pared gástrica, pero que luego de la realización de una adecuada historia clínica, complementada con imágenes diagnósticas y avances ecoendoscópicos, se logró el diagnóstico de metástasis de cáncer de endometrio.

Abstract Endometrial cancer is the most common gynecologic malignancy in women. Its metastatic presentation is mainly limited to neighboring organs and nearby lymph nodes, and infiltration of the upper digestive tract is uncommon. This case report depicts a patient admitted to the emergency department with upper gastrointestinal bleeding symptoms. Initially, a gastrointestinal stromal tumor (GIST) of the gastric wall was suspected, but endometrial cancer metastasis was discovered after a thorough medical examination, diagnostic imaging, and echoendoscopes.

Caracterización de paciente con tumores estromales gastrointestinales en Hospital Clínico-Quirúrgico "Arnaldo Milián Castro" / Characterization of Patients with Stromal Gastrointestinal Tumors in Arnaldo Milián Castro Clinical-Surgical Hospital

Introducción: El tumor estromal gastrointestinal es la neoplasia mesenquimal más frecuente en el tracto digestivo, su diagnóstico y tratamiento aun es controvertido por ser infrecuente. Objetivo: Caracterizar los pacientes con tumores estromales gastrointestinales atendidos en nuestro servicio. Métodos: Se realizó un estudio observacional descriptivo longitudinal en pacientes con tumores estromales gastrointestinales atendidos en el servicio de cirugía del Hospital Clínico-Quirúrgico "Arnaldo Milián Castro" desde 2015 hasta 2018. La muestra fue de 17 pacientes. Resultados: Predominaron los pacientes entre 60 y 69 años (35,3 por ciento) del sexo femenino (58,82 por ciento). El dolor abdominal como síntoma más frecuente (58,82 por ciento). El (47,1 por ciento) de los tumores midieron más de 10 cm, celularidad fusiforme (58,8 por ciento), índice mitótico menor de 5 (70,6 por ciento), sin patrón de crecimiento infiltrante (70,6 por ciento). La metástasis ausente en el (82,4 por ciento). Presente con igual frecuencia en estómago e intestino delgado (N = 8), fue igual la presencia de comportamiento agresivo bajo y alto (35,3 por ciento). Predominaron los marcadores CD.117 (41,2 por ciento) y CD.34 (35,3 por ciento). La recesión segmentaria de intestino delgado con anastomosis término-terminal fue la técnica quirúrgica más empleada (35,3 por ciento). Conclusiones: A pesar de ser mayormente grandes y encontrarse en porciones altas del tubo digestivo, muchos presentaron índice mitótico bajo, no obstante, un grupo considerable presentó comportamiento agresivo. Si bien es cierto que casi la totalidad de pacientes egresaron vivos, falta un seguimiento en el centro, lo cual resultaría interesante evaluar en futuros estudios(AU)

Introduction: Gastrointestinal stromal tumor is the most frequent mesenchymal neoplasm in the digestive tract, its diagnosis and treatment is still controversial because it is infrequent. Objective: To characterize the patients with gastrointestinal stromal tumors treated in our service. Methods: A longitudinal descriptive observational study was carried out in patients with gastrointestinal stromal tumors treated in the surgery service of the "Arnaldo Milián Castro" Clinical-Surgical Hospital from 2015 to 2018. The sample consisted of 17 patients. Results: Female patients between 60 and 69 years old (35.3 percent) predominated (58.82 percent). Abdominal pain as the most frequent symptom (58.82 percent). Tumors (47.1 percent) measured more than 10 cm, spindle cell cellularity (58.8 percent), mitotic index less than 5 (70.6 percent), and no infiltrative growth pattern (70.6 percent). Metastasis absent in (82.4 percent). Present with equal frequency in the stomach and small intestine (N = 8), the presence of low and high aggressive behavior (35.3 percent) was the same. The markers CD.117 (41.2 percent) and CD.34 (35.3 percent) predominated. Segmental recession of the small intestine with end-to-end anastomosis was the most widely used surgical technique (35.3 percent). Conclusions: Despite being mostly large and found in high portions of the digestive tract, many presented a low mitotic index, however, a considerable group presented aggressive behavior. Although it is true that almost all the patients were discharged alive, there is a lack of follow-up at the center, which would be interesting to evaluate in future studies(AU)

Multiple Gastrointestinal Stromal Tumor with Neurofibromatosis Type Ⅰ:Report of One Case / 中国医学科学院学报

Gastrointestinal stromal tumors(GISTs)in the stomach,duodenum,and rectum have low occurrence,and the coexistence GISTs in three parts with neurofibromatosis type Ⅰ(NF-Ⅰ)is even rare.This paper reports a case of GISTs with a family history of NF-Ⅰ.There were multiple nodular masses of different sizes on the patient's face,trunk,and limbs.The patient was admitted due to chest tightness for 5 days and black stools for 1 day.Enhanced CT examination of the abdomen suggested multiple space-occupying lesions in the upper abdomen with multiple small nodules under the abdominal wall,and neurofibromatosis and intestinal stromal tumor cannot be excluded.Finally,surgical pathology confirmed that the multiple tumors in the abdominal cavity were GISTs.The case was confirmed as wild-type GISTs by genetic testing,and the patient recovered well nearly one year after the operation.

Molecular mechanism study of Shouhui Tongbian Capsules on promoting energy metabolism of gastrointestinal stromal cells / 中国中药杂志

Mechanism study was performed to explore how Shouhui Tongbian Capsules promotes energy metabolism of gastrointestinal stromal cells. In this study, gastrointestinal stromal cells line GIST-882 was used as the model to explore energy metabolism regulation effects of Shouhui Tongbian Capsules extract(10, 20, 50 and 100 μg·mL~(-1)) by measuring the cell proliferation, ATP level, mitochondrial membrane potential, and mitochondrial isocitrate dehydrogenase activity. Meanwhile, Western blot was used to detect the proteins expression of SCF/c-Kit and CDK2/cyclin A signaling pathways. Our results showed that Shouhui Tongbian Capsules promoted cell proliferation and increased ATP level of gastrointestinal stromal cells. In addition, Shouhui Tongbian Capsules obviously improved mitochondrial structural integrity, and increased mitochondrial membrane potential in GIST-882 cells. Mechanism study revealed that Shouhui Tongbian Capsules increased mitochondrial isocitrate dehydrogenase activity and up-regulated the proteins expression of SCF/c-Kit and CDK2/cyclin A signaling pathways. Collectively, our study indicated that Shouhui Tongbian Capsules promoted the energy metabolism for gastrointestinal stromal cells proliferation by activating mitochondrial isocitrate dehydrogenase to induce ATP production, as well as activating SCF/c-Kit and CDK2/cyclin A signaling pathways.

Treatment strategy of gastrointestinal stromal tumors in the background of COVID-19 / 中华胃肠外科杂志

COVID-19, caused by SARS-COV-2, has the characteristics of world epidemic, highly infectious and large base of death. In China, transmission route of SARS-COV-2 has been contained so effectively that COVID-19 has been well controlled due to the proactive national prevention and control strategy. However, not only does it bring a huge impact on the existing medical structure model, but also an objective impact on the treatment of patients with chronic diseases such as malignant tumors. Based on the progress reported in the domestic and international literatures and the actual management experience of our team, this paper reflects on the treatment strategies for patients with gastrointestinal stromal tumor (GIST) during the epidemic period of COVID-19. We focus on risk stratification for primary GIST and forming treatment strategies accordingly. Major considerations include the impact of delayed operation, the burden of medical resources, the waiting time for elective operation, and the principle of emergency operation. In addition, we focus on the level of evidence for non-surgical approaches with a view to developing a holistic strategy of "priority management principles" to guide clinical treatment in the context of limited resources and different GIST priorities.

Identification and inner relation between gastrointestinal stromal tumor and intra-abdominal desmoid tumor / 中华胃肠外科杂志

Intra-abdominal desmoid tumor (IADT) and gastrointestinal stromal tumor (GIST) are both mesenchymal tumors mostly found in gastrointestinal tracts and easily misdiagnosed, which would directly damage the survival prognosis and quality of life of patients. With the advent of the era of precision medicine, the understanding of the above two diseases is more in-depth, and the requirements for accurate diagnosis and individualized precision treatment are more stringent. Moreover, there seems to be some internal relationship between IADT and GIST, and the lack of systematic research and discussion makes clinical decision-making and patient management easy to fall into traps and misunderstandings. Therefore, this paper reviews the clinical characteristics, pathogenesis and treatments of the two, and explore their differences and internal relations, so as to provide research and practical reference for promoting more precise and individualized diagnosis and treatment regimens.

Clinicopathological features and prognosis of gastrointestinal stromal tumors with KIT/PDGFRA gene "homozygous mutation": a multicenter retrospective cohort study / 中华胃肠外科杂志

Objective: To investigate the clinicopathological features of gastrointestinal stromal tumor (GIST) with KIT/PDGFRA "homozygous mutation", the efficacy of targeted therapy and the prognosis. Methods: A retrospective cohort study and propensity score matching were used. "Homozygous mutation" was defined as the detection of KIT/PDGFRA gene status of GIST by Sanger sequencing, which showed that there was only mutant gene sequence in the sequencing map, lack of wild-type sequence or the peak height of mutant gene sequence was much higher than that of wild-type gene sequence (> 3 times). "Heterozygous mutation" was defined as the mutant gene sequences coexisted with wild type gene sequences, and the peak height was similar (3 times or less). The clinicopathological data and follow-up information of 92 GIST patients with KIT/PDGFRA "homozygous mutation" were collected from 4 hospitals in Shanghai from January 2008 to May 2021 (Renji Hospital, Shanghai Jiaotong University School of Medicine: 70 cases; Zhongshan Hospital, Fudan University: 14 cases; Changhai Hospital, Naval Military Medical University: 6 cases and Ruijin Hospital, Shanghai Jiaotong University School of Medicine: 2 cases). Patients with perioperative death, other malignancies, and incomplete clinicopathological information were excluded. The clinicopathological features of the patients and the efficacy of targeted drug therapy were observed and analyzed. The efficacy was evaluated using Choi criteria, which were divided into complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). In addition, a total of 230 patients with high-risk GIST with "heterozygous mutation" in exon 11 of KIT gene and 117 patients with recurrent or metastatic GIST with "heterozygous mutation" in exon 11 of KIT gene were included. The propensity score matching method was used to match GIST patients with "heterozygous" and "homozygous" mutations in exon 11 of KIT gene (1∶1) for survival analysis. The disease-free survival (DFS) between two groups of high-risk GIST patients who underwent complete surgical resection were compared. And progression-free survival (PFS) in patients with recurrent or metastatic GIST were compared. Results: Of the 92 GIST cases with KIT/PDGFRA "homozygous mutation", 58 were males and 34 were females, with a median onset age of 62 (31-91) years. Primary GIST 83 cases. Primary high-risk GIST (53 cases), metastatic GIST (21 cases) and recurrent GIST (9 cases) accounted for 90.2% (83/92). There were 90 cases of KIT gene"homozygous mutation" (exon 11 for 88 cases, exon 13 for 1 case, exon 17 for 1 case), and 2 cases of PDGFRA gene "homozygous mutation" (exon 12 for 1 case, exon 18 for 1 case). The median follow-up time was 49 (8-181) months. Among the 61 cases of primary localized GIST undergoing complete surgical resection, 2 cases were intermediate-risk GIST, 5 cases were low-risk GIST, and 1 case was very low-risk GIST, of whom 1 case of intermediate-risk GIST received 1-year adjuvant imatinib mesylate (IM) therapy after operation, and no tumor recurrence developed during the follow-up period. The remaining 53 cases were high-risk GIST, and follow-up data were obtained from 50 cases, of whom 22 developed tumor recurrence during follow-up. Of 9 patients directly receiving neoadjuvant targeted therapy (IM or avapritinib), 5 had complete imaging follow-up data, and the evaluation of efficacy achieved PR. Of all the 92 GIST cases with KIT/PDGFRA "homozygous mutation", 50 (54.4%) had tumor metastasis or tumor recurrence or progression during follow-up, and 12 (13.0%) died of the tumor. Survival analysis combined with propensity score showed that in 100 cases of high-risk GISTs with complete resection, GISTs with "homozygous mutation" in exon 11 of KIT gene had shorter disease-free survival (DFS) than GISTs with "heterozygous mutation" in exon 11 of KIT gene (median DFS: 72 months vs. 148 months, P=0.015). In 60 cases of recurrent or metastatic GISTs with KIT gene exon 11 mutation, IM was used as the first-line treatment, and the progression-free survival (PFS) of GISTs with "homozygous mutation" was shorter compared to GISTs with "heterozygous mutation" (median PFS: 38 months vs. 69 months, P=0.044). The differences were statistically significant. Conclusions: "Homozygous mutation" in KIT/PDGFRA gene is associated with the progression of GIST. The corresponding targeted therapeutic drugs are still effective for GIST with KIT/PDGFRA gene "homozygous mutation". Compared with GIST patients with "heterozygous mutation" in KIT exon 11, GIST patients with "homozygous mutation" in KIT exon 11 are more likely to relapse after surgery and to develop resistance to IM. Therefore, it is still necessary to seek more effective treatment methods for this subset of cases.

Clinical significance of the deep learning algorithm based on contrast-enhanced CT in the differential diagnosis of gastric gastrointestinal stromal tumors with a diameter ≤ 5 cm / 中华胃肠外科杂志

Objective: Contrast-enhanced CT is an important method of preoperative diagnosis and evaluation for the malignant potential of gastric submucosal tumor (SMT). It has a high diagnostic accuracy rate in differentiating gastric gastrointestinal stromal tumor (GIST) with a diameter greater than 5 cm from gastric benign SMT. This study aimed to use deep learning algorithms to establish a diagnosis model (GISTNet) based on contrast-enhanced CT and evaluate its diagnostic value in distinguishing gastric GIST with a diameter ≤ 5 cm and other gastric SMT before surgery. Methods: A diagnostic test study was carried out. Clinicopathological data of 181 patients undergoing resection with postoperative pathological diagnosis of gastric SMT with a diameter ≤ 5 cm at Department of Gastrointestinal Surgery of Renji Hospital from September 2016 to April 2021 were retrospectively collected. After excluding 13 patients without preoperative CT or with poor CT imaging quality, a total of 168 patients were enrolled in this study, of whom, 107 were GIST while 61 were benign SMT (non-GIST), including 27 leiomyomas, 24 schwannomas, 6 heterotopic pancreas and 4 lipomas. Inclusion criteria were as follows: (1) gastric SMT was diagnosed by contrast-enhanced CT before surgery; (2) preoperative gastroscopic examination and biopsy showed no abnormal cells; (3) complete clinical and pathological data. Exclusion criteria were as follows: (1) patients received anti-tumor therapy before surgery; (2) without preoperative CT or with poor CT imaging quality due to any reason; (3) except GIST, other gastric malignant tumors were pathologically diagnosed after surgery. Based on the hold-out method, 148 patients were randomly selected as the training set and 20 patients as the test set of the GISTNet diagnosis model. After the GISTNet model was established, 5 indicators were used for evaluation in the test set, including sensitivity, specificity, positive predictive value, negative predictive value and the area under the receiver operating curve (AUC). Then GISTNet diagnosis model was compared with the GIST-risk scoring model based on traditional CT features. Besides, in order to compare the accuracy of the GISTNet diagnosis model and the imaging doctors in the diagnosis of gastric SMT imaging, 3 radiologists with 3, 9 and 19 years of work experience, respectively, blinded to clinical and pathological information, tested and judged the samples. The accuracy rate between the three doctors and the GISTNet model was compared. Results: The GISTNet model yielded an AUC of 0.900 (95% CI: 0.827-0.973) in the test set. When the threshold value was 0.345, the sensitivity specificity, positive and negative predictive values of the GISTNet diagnosis model was 100%, 67%, 75% and 100%, respectively. The accuracy rate of the GISTNet diagnosis model was better than that of the GIST-risk model and the manual readings from two radiologists with 3 years and 9 years of work experience (83% vs. 75%, 60%, 65%), and was close to the manual reading of the radiologist with 19 years of work experience (83% vs. 80%). Conclusion: The deep learning algorithm based on contrast-enhanced CT has favorable and reliable diagnostic accuracy in distinguishing gastric GIST with a diameter ≤ 5 cm and other gastric SMT before operation.

Significance of circulating tumor cell monitoring in targeted therapy for gastrointestinal stromal tumors / 中华胃肠外科杂志

Objective: To explore the significance of circulating tumor cell (CTC) monitoring in evaluating the efficacy of targeted therapy for gastrointestinal stromal tumor (GIST). Methods: A prospective cohort study was performed. The data of patients with locally advanced GIST or liver metastasis who were admitted to The Affiliated Hospital of Nantong University from August 2013 to December 2018 were collected. Inclusion criteria: (1) patients aged older than 18 years; (2) patients who were diagnosed with GIST based on pathology; (3) patients without surgery, whose preoperative imaging evaluation of GIST found the violations of the surrounding organs or partial transfer of an estimated difficulty to achieve R0 resection, or the maximum diameter of the tumor > 10 cm, or the liver metastasis, or the expectation of higher risk of surgical complications; (4) patients who were treated with the imatinib 400 mg/d for the first time; (5) Eastern Cooperative Oncology Group (ECOG) score of 0-2. Exclusion criteria: (1) genetic testing revealed a D842V mutation in exon 18 of the PDGFRA gene; (2) alanine aminotransferase and/or aspartate aminotransferase > 2.5 times the normal upper limit; (3) serum total bilirubin >1.5 times of normal upper limit; (4) neutrophil count < 1.5×10(9)/L, or platelet count < 75×10(9)/L, or hemoglobin < 60 g/L; (5) creatinine > normal upper limit; (6) patients had serious cardiovascular and cerebrovascular diseases within 12 months before enrollment; (7) female patients were pregnant or lactating; (8) patients suffered from other serious acute and chronic physical or mental problems, and were not suitable for participating in this study judged by researchers. The patients who could not tolerate treatment regimen, or developed serious adverse reactions and did not follow the medication scheme after enrollment were excluded. Before imatinib treatment and 1-month and 2-month after treatment, quantitative PCR was used to detect the DOG-1 expression of monocytes in peripheral blood, and the ratio of DOG-1/β-actin > 3×10(-5) was used as the CTC positive threshold of GIST. The positive rate of CTC, the efficacy of imatinib treatment (complete response, partial response, stable disease, progressive disease, and occurrence of adverse reactions), and the relationship between CTC positive rate and clinicopathological characteristics of patients were analyzed. Furthermore, the ratio of DOG-1 decrease/baseline DOG-1 after 1-month of treatment was used as an indicator to evaluate whether targeted therapy was effective. The receiver operating characteristic (ROC) curve was rendered, and the area under the curve (AUC) was calculated. Results: A total of 68 GIST patients were enrolled in this study, including 39 cases of locally advanced GIST and 29 cases with liver metastases, 32 males and 36 females with the mean age of (51.2±11.8) (range 31 to 74) years. After 2-month of imatinib treatment, 43 cases were evaluated as partial response, 11 cases as stable disease, and 14 cases as progressive disease, with an effective rate of 79.4% (54/68). During the treatment of imatinib, the incidence of grade 3 or higher adverse reactions was 22.1% (15/68), including 12 cases of grade 3 neutropenia and 3 of grade 4 drug eruption, which were all relieved after conservative treatment. The positive rates of CTC in 68 patients before treatment, 1-month and 2-month after treatment were 66.2% (45/68), 41.2% (28/68) and 23.5% (16/68), respectively. The positive rate of CTC was associated with tumor size, liver metastasis, mitotic count and risk level (all P<0.05). By analyzing the effective group and the ineffective group of targeted therapy, it was found that the positive rate of CTC in the effective group showed a decreasing trend, while the positive rate of CTC in the ineffective group showed an increasing trend. The AUC of predicting the efficacy of targeted therapy for GIST was 0.823 by detecting the change trend of CTC 1-month after treatment (P<0.001). When the DOG-1 content decreased by more than 57.5% 1-month after treatment, it can be used as an indicator to judge the effectiveness of the treatment, whose sensitivity was 72.2% and specificity was 100%. Conclusion: The detection of peripheral blood CTC can evaluate the efficacy of targeted therapy in GIST patients and can provide decision-making basis for further clinical treatment.

Clinicopathological characteristics and prognosis of patients with sporadic multiple primary gastrointestinal stromal tumors / 中华胃肠外科杂志

Objective: To investigate the clinicopathological characteristics and prognosis of sporadic multiple primary gastrointestinal stromal tumor (GIST). Methods: A retrospective cohort study was conducted. Case inclusion criteria: (1) postoperative pathological diagnosis of GIST; (2) primary GIST with single lesion or sporadic multiple primary GIST (sporadic GIST was defined as primary GIST other than familial and syndrome-related GIST, and multiple primary GIST was defined as the number of primary GISTs in the same patient ≥ 2); (3) patients with complete clinicopathological data. Those with tumor recurrence or distant metastasis, and with other malignancies were excluded. Medical records of patients with primary GIST who underwent surgical resection in the Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from January 2010 to December 2020 were collected. Patients were divided into sporadic multiple primary GIST group and single primary GIST group according to the number of primary GIST lesions. The clinicopathological data and prognosis of the two groups were observed and compared. Results: A total of 1200 patients with primary GIST were enrolled in this study, including 628 males (52.3%) and 572 females (47.7%), with a median onset age of 58 (19-93) years. Among them, 1165 cases (97.1%) were sporadic primary GIST with single lesion; 35 cases (2.9%) were sporadic multiple primary GIST. Among 35 cases of sporadic multiple primary GIST, 3 cases (8.6%) had acid reflux as the first symptom, which was higher than the single primary GIST group (22/1165, 1.9%) (χ(2)=7.437, P=0.006). There were no significant differences in other clinical characteristics between the two groups (all P>0.05). Patients in the sporadic multiple primary GIST group contained a total of 80 primary tumors. Compared with the single primary GIST group, the sporadic multiple primary GIST group had a higher proportion of tumors originating in the stomach [87.5% (70/80) vs. 59.1% (689/1165)], lower proportion of spindle cell in histology [85.0% (68/80) vs. 93.7% (1092/1165)], higher proportion of positive CD34 [97.5% (78/80) vs. 87.6% (1021/1165)], smaller maximum diameter [maximum diameter ≤2.0 cm: 61.2% (49/80) vs. 28.8% (335/1165)], lower mitotic rate [≤5/50 high-power fields (HPF): 93.8% (75/80) vs. 74.5% (868/1165)], lower risk of recurrence [60.0% (48/80) vs. 23.3% (271/1165)], and the differences were all statistically significant (all P<0.05). The 3-year recurrence-free survival rate in the sporadic multiple primary group and the single primary GIST group was 96.6% and 89.3% respectively (P=0.160), and the 3-year overall survival rate was 100.0% and 92.8%, respectively (P=0.088). Conclusions: The most common type of sporadic multiple primary GIST is multiple tumors originating in the stomach at the same time. Compared with primary GIST with single lesion, sporadic multiple primary GIST presents smaller maximum diameter and lower mitotic rate. The prognosis of patients between two groups is not significantly different.