Research progress on drug treatment and drug resistance mechanism of gastrointestinal stromal tumors / 中国临床药理学与治疗学

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal-derived tumors of the gastrointestinal tract. Tyrosine kinase inhibitors (TKIs) are the cornerstone of GIST therapy, but mutations in resistance genes pose many problems for treatment, especially the heterogeneity of KIT resistance mutations. In recent years, with the release of a number of GIST related drug research and experimental results, the great potential of targeted therapy, immunotherapy and combination therapy to treat GIST in different directions has been revealed, providing more therapeutic directions for GIST. This article will review the experimental research and future direction in recent years.

Antral plexiform fibromyxoma: case report of a rare mesenchymal neoplasm

Plexiform fibromyxoma (PF) is a rare mesenchymal neoplasm of the stomach usually arising in the gastric antrum, and its main differential diagnosis is gastrointestinal stromal tumor. Most common symptoms are hematemesis, anemia. Immunohistochemically, positivity for smooth muscle actin (SMA) and vimentin suggests the diagnosis of PF. We report the case of a 56-year-old female patient with a 30- day history of nausea at presentation 4 years ago. Gastroscopy at that time revealed a subepithelial lesion (SEL) in the gastric antrum, measuring approximately 20 mm in diameter, with leakage of serous fluid after biopsy. Histopathology showed only an inflammatory process. Follow-up gastroscopies were performed 24, 36, and 48 months later, with surveillance biopsy at each follow-up. The last gastroscopies showed changes in lesion appearance, reduction in size, and absence of fluid leakage. Histopathology showed bland spindle cell proliferation, with a vaguely plexiform/multinodular pattern, in a fibromyxoid stroma with an arborizing capillary network without mitoses. The tumor cells were positive for SMA and negative for DOG1, CD117, CD34, S100, desmin, EMA, CD10, calponin, and beta-catenin. The choice of treatment and follow-up depends on the SEL features, but because no cases of malignancy or metastatic disease have previously been reported, the patient chose a conservative approach.

El fibromixoma plexiforme (FP) es una rara neoplasia mesenquimatosa del estómago que generalmente surge en el antro gástrico. Su principal diagnóstico diferencial es el tumor del estroma gastrointestinal. Los síntomas más comunes de los FP son hematemesis y anemia. Inmunohistoquímicamente, la positividad para actina del músculo liso (SMA) y vimentina sugieren el diagnóstico de FP. Presentamos el caso de una paciente de 56 años de edad que inicia su enfermedad hace 4 años con náuseas de 30 días de evolución. La primera gastroscopia reveló una lesión subepitelial (SEL) en el antro gástrico, de aproximadamente 20 mm de diámetro, con fuga de líquido seroso después de la biopsia. La histopatología mostró sólo un proceso inflamatorio. Se realizaron gastroscopias de seguimiento a los 24, 36 y 48 meses con biopsia de vigilancia en cada seguimiento. Las gastroscopias siguientes mostraron cambios en la apariencia de la lesión, reducción de tamaño y ausencia de fuga de líquido. La última histopatología mostró una proliferación blanda de células fusiformes, con un patrón vagamente plexiforme/multinodular, en un estroma fibromixoide con una red de capilares arborizantes sin mitosis. Las células tumorales fueron positivas para SMA y negativas para DOG1, CD117, CD34, S100, desmina, EMA, CD10, calponina y beta-catenina. La elección del tratamiento y el seguimiento depende de las características del SEL, sin embargo, por ser una enfermedad que no presentaba rasgos de enfermedad maligna o metastásica, el paciente eligió un mantener un enfoque conservador.

Hemorragia de intestino delgado en un paciente con Neurofibromatosis tipo 1

Presentamos el caso de un paciente masculino de 32 años con antecedente de Neurofibromatosis tipo 1, que se presenta por hemorragia de intestino delgado activo, diagnosticada inicialmente al observar sangrado en ileoscopía, al cursar con inestabilidad hemodinámica se realiza angiotomografía abdominal identificando a nivel de yeyuno medio una masa con captación de contraste y sangrado activo por lo cual se realiza una angiografía con embolización arterial de la rama que irriga dicha zona. Con el paciente estable, se realizó una enteroscopía anterógrada de doble balón, observando una lesión subepitelial, ulcerada, se realiza tatuaje endoscópico y finalmente se envía a cirugía para resección mediante laparoscopia. El estudio anatomopatológico fue compatible con un tumor estromal gastrointestinal (GIST) yeyunal.

We present the case of a 32-year-old male patient with a history of Neurofibromatosis type 1, who presented with active small bowel bleeding, initially diagnosed by observing bleeding in ileoscopy, presenting with hemodynamic instability, abdominal angiotomography was performed, identifying a mass with contrast enhancement and active bleeding at the middle jejunum level, for which an angiography with arterial embolization of the branch that supplies said area is performed. With the patient stable, a double-balloon antegrade enteroscopy was performed, observing a subepithelial, ulcerated lesion, endoscopic tattooing was performed and finally surgery was sent for resection by laparoscopy. The pathology study was compatible with a jejunal gastrointestinal stromal tumor (GIST).

Estrategia quirúrgica en un paciente con tumor agresivo del tracto gastrointestinal en cuarta porción de duodeno

Los tumores del estroma gastrointestinal son tumores infrecuentes y se corresponden con un 1 % de todas las neoplasias gastrointestinales; la localización duodenal solo representa entre 3-5 %. Se realizó este reporte de caso con el propósito de divulgar la estrategia quirúrgica seguida con un paciente portador de tumor invasivo del estroma gastrointestinal (>10 cm) de localización atípica, en cuarta porción del duodeno. El internamiento fue por tumor abdominal y anemia. El ejercicio clínico consistió en identificar una masa abdominal izquierda con contacto lumbar. Las pruebas diagnósticas realizadas fueron: pruebas de química sanguínea, ultrasonido abdominal, tomografía axial computadorizada y endoscopia digestiva con biopsia que confirmó el diagnóstico. El procedimiento quirúrgico fue resección de la cuarta porción de duodeno y primeras asas yeyunales, con restablecimiento de la funcionabilidad intestinal mediante duodeno (segunda porción)-yeyunostomía latero-lateral. La cirugía fue interrumpida por inestabilidad hemodinámica del paciente y cuatro días después fue llevado otra vez al salón de operaciones por presentar peritonitis, con salida de pus por los drenajes abdominales, que fue solucionada con lavado de la cavidad. La morbilidad estuvo acompañada por una fístula pancreática. En el tercer tiempo quirúrgico se realizó resección del tumor residual, nefrectomía izquierda y control de la fístula pancreática. Después de un año el paciente se encuentra libre de enfermedad tumoral. Se puede concluir que la estrategia de manejo en pacientes con tumores del estroma gastrointestinal de localización atípica representa un reto para el cirujano como miembro del grupo multidisciplinar y depende de la extensión del tumor, el estado del paciente y el manejo oportuno del equipo quirúrgico.

Gastrointestinal stromal tumors are rare tumors and correspond to 1% of all gastrointestinal neoplasms; duodenal location only represents between 3-5%. This case report was made for disclosing the surgical strategy followed in a patient with invasive gastrointestinal stromal tumors (>10 cm) of atypical location in the duodenum fourth portion. Hospitalization was due to abdominal tumor and anemia. The clinical exercise consisted of identifying a left abdominal mass with lumbar contact. The diagnostic tests performed were: blood chemistry tests, abdominal ultrasound, computerized axial tomography, and digestive endoscopy with biopsy that confirmed the diagnosis. The surgical procedure was resection of the duodenum fourth portion and the first jejunal loops, with restoration of intestinal function through duodenum (second portion) lateral jejunostomy. The surgery was interrupted due to the patient's hemodynamic instability, and four days later he was taken back to the operating room due to peritonitis, with pus coming out of the abdominal drains, which was resolved by washing the cavity. Morbidity was accompanied by a pancreatic fistula. In the third surgical time, resection of the residual tumor, left nephrectomy, and control of the pancreatic fistula were performed. After one year the patient is free of tumor disease. The management strategy in patients with atypically located gastrointestinal stromal tumors represents a challenge for the surgeon as a member of the multidisciplinary group and depends on the extent of the tumor, the patient's condition, and the surgical team timely management.

Application of forward-return way in endoscopic resection for gastric fundus stromal tumor (with video) / 中华消化内镜杂志

To evaluate the value of forward-return way in endoscopic resection for the treatment of gastric fundus stromal tumor, patients with gastric fundus stromal tumor in muscularis propria diagnosed by endoscopy and endoscopic ultrasonography at the Department of Digestive Endoscopy of the Fourth Affiliated Hospital of China Medical University from June 2020 to June 2021 were prospectively enrolled in the study. All patients were treated with endoscopic full-thickness resection under general anesthesia with endotracheal intubation. The success of forward-return way, endoscopic procedure, operation performance, pathological classifications and complications were analyzed. A total of 12 patients were enrolled. All of them were confirmed as having stromal tumor by postoperative pathology, with 10 of very low risk and 2 of low risk. Forward-return way was successful in 9 patients and failed in 3 patients. Nine patients were successfully treated with endoscopic procedure eventually. No intraoperative bleeding occurred in any patient. In endoscopic resection, the scores of same direction of forward and backward, endoscopic field of view, and endoscopic body stability were all 2.00 points. Forward-return way has clinical application value for the endoscopic treatment of gastric fundus stromal tumor.

Comparison between endoscopic full-thickness resection and cap-assisted endoscopic full-thickness resection in the treatment of elderly patients with small gastric stromal tumors / 中华消化内镜杂志

Objective:To compare the safety and effectiveness of endoscopic full-thickness resection (EFR) and cap-assisted endoscopic full-thickness resection (EFR-C) in the treatment of small gastric stromal tumors (≤1.5 cm) in the elderly (≥60 years old).Methods:Data of elderly patients with small gastric stromal tumors who received EFR (41 cases) or EFR-C (25 cases) at Nanjing Drum Tower Hospital from May 2012 to August 2020 were analyzed retrospectively. The clinicopathological characteristics, the procedures, intraoperative and postoperative complications, postoperative efficacy and economic benefits were compared between the two groups.Results:The R0 resection rates of the EFR group and the EFR-C group were 95.1% (39/41) and 100% (25/25), respectively. The operation time [45.0 (32.5, 66.5) min VS 30.0 (20.0, 42.5) min, U=259.500, P=0.001] and resection time [30.0 (20.0, 50.5) min VS 9.0 (6.5, 16.5) min, U=127.000, P<0.001] of the EFR group were significantly longer than those of the EFR-C group. The rate of hot clamp use in the EFR group was higher than that in the EFR-C group [75.6% (31/41) VS 12.0% (3/25), χ ２=25.159, P<0.001]. The postoperative white blood cell count [8.3 (6.6,10.4)×10 9/L VS 6.3 (5.0,7.7) ×10 9/L, U=271.000, P=0.001] and postoperative neutrophil percentage (77.6%±8.8% VS 73.0%±6.8%, t=2.256, P=0.027) in the EFR group were higher than those in the EFR-C group. The postoperative antibiotic day in the EFR group was longer than that in the EFR-C group (2.8±2.0 days VS 1.0±2.0 days, t=3.625, P=0.001). The hospitalization costs in the EFR group were significantly higher than those in the EFR-C group (20 595.0±3 653.3 yuan VS 13 209.0±4 458.9 yuan, t=7.323, P<0.001). There was no recurrence or metastasis during the follow-up period. Conclusion:EFR and EFR-C are safe and effective for the treatment of small gastric stromal tumors in the elderly. Compared with EFR, EFR-C needs shorter operation time and lower medical costs, yields less postoperative inflammation, and is more suitable for the treatment of small gastric stromal tumors in the elderly.

A diagnostic prediction nomogram for small gastric stromal tumors based on features under endoscopic ultrasonography / 中华消化内镜杂志

Objective:To establish a nomogram based on features under endoscopic ultrasonography (EUS) for predicting the diagnosis of small gastric stromal tumors.Methods:The clinicopathological data of 189 patients with gastric submucosal tumors (diameter less than 2 cm) who underwent endoscopic resection at the Department of Gastroenterology, Tongji Hospital of Tongji University from June 2015 to August 2021 were retrospectively collected. All patients were divided into the modeling group ( n=126) and the validation group ( n=63) at 2∶1 by random function of software R. Independent influencing factors for the diagnosis of small gastric stromal tumors under EUS screened by univariable and multivariable logistic regression analysis were used to establish the diagnostic prediction nomogram. The receiver operator characteristic (ROC) curves were drawn to evaluate the discrimination of the model both in the modeling group and the validation group. Hosmer-Lemeshow test and calibration curve were used to evaluate the calibration of the model in both groups. Results:The age of patients >60 years ( OR=2.815, 95% CI:1.148-6.900, P=0.024), the lesions located in cardia/fundus ( OR=5.210, 95% CI:1.225-22.165, P=0.025), originated in muscularis propria ( OR=6.404, 95% CI:2.262-18.135, P<0.001) and of external growth ( OR=6.024, 95% CI:1.252-28.971, P=0.025) were independent influencing factors for the diagnosis of small gastric stromal tumors under EUS. The diagnostic prediction nomogram was established based on the four factors above. The areas under ROC curve of the modeling group and validation group were 0.834 (95% CI:0.765-0.903) and 0.780 (95% CI:0.667-0.893). Hosmer-Lemeshow test indicated that this model fit the data well ( χ2=10.23, P=0.176 in the modeling group; χ2=2.62, P=0.918 in the validation group). Calibration charts of the model drawn by Bootstrap method showed that the calibration curves fit well with the standard curves in both groups. Conclusion:The nomogram based on features under EUS for predicting the diagnosis of small gastric stromal tumors provides a visual reference for endoscopists to diagnose small gastric stromal tumors under EUS with good discrimination and calibration.

CT features of gastric stromal tumors in predicting Ki-67 index expression / 中华普通外科杂志

Objective:To investigate the feasibility of multi-slice spiral CT (MSCT) imaging feature of gastric stromal tumor (GST) in evaluating Ki-67 index expression .Methods:The clinical and CT imaging data of 501 patients with GST confirmed by surgery and pathology were retrospectively studied in Zhongshan Hospital affiliated to Fudan University and the Affiliated TCM Hospital of Southwest Medical University from Nov 2014 to Nov 2021. By immunohistochemical results, tumors were divided into Ki-67 low expression group (Ki-67≤6%, 335 lesions) and high expression group (Ki-67>6%, 168 lesions). Multivariate logistic regression analysis was conducted.Results:Between the two groups,there were statistical differences in the longest and shortest diameter of tumor, CT value on venous phase, CT attenuation value ( Z=4.80, 4.91, 3.21, 3.29, all P<0.01) and tumor location,morphology, necrosis, ulcer, feeding artery, vascular enhancement, positive fat sign around disease, gastrointestinal bleeding ( χ2=10.77, 13.49, 8.59, 22.87, 7.59, 7.23, 7.76, 8.58, all P<0.05). Tumor ulceration positive ( OR=1.88, 95%CI: 1.17-3.03) was independent risk factor of Ki-67 high expression ( P=0.009). Gastric antrum was used as the reference for tumor location, cardia ( OR=5.41, 95% CI:1.25-23.46) was independent risk factor of Ki-67 high expression ( P=0.024). Conclusion:MSCT has a definite predictive value for the expression in Ki-67 index of GST cases.

Predictive values of 18F-FDG PET/CT image feature and metabolic parameters for the malignant potential of gastrointestinal stromal tumor / 中华核医学与分子影像杂志

Objective:To investigate the predictive values of 18F-FDG PET/CT image feature and metabolic parameters for the malignant potential of gastrointestinal stromal tumor (GIST). Methods:From March 2014 to June 2020, the 18F-FDG PET/CT imaging and surgical pathological data of 35 patients with GIST (27 males, 8 females; age 44-84 years) from Union Hospital, Tongji Medical College, Huazhong University of Science and Technology and Zhongnan Hospital of Wuhan University were analyzed retrospectively. Patients were divided into ring-shaped uptake group and other uptake patterns group according to 18F-FDG PET/CT image feature. Fisher′s exact test was used to analyze the differences of tumor necrosis and National Institutes of Health (NIH) risk classification (short for NIH classification) between different image feature groups. Mann-Whitney U test was used to analyze the differences of SUV max , metabolic parameters at different thresholds (2.5, 40%, 50%) of SUV max (metabolic tumor volume (MTV; MTV 2.5, MTV 40%, MTV 50%) and total lesion glycolysis (TLG; TLG 2.5, TLG 40%, TLG 50%)) between different clinicopathological features (lesion location, tumor diameter, mitotic count, Ki-67, necrosis, image feature, NIH classification) groups. Spearman rank correlation analysis was used to explore the correlation between clinicopathological features and metabolic parameters. ROC curve analysis was used to distinguish NIH classification of different metabolic parameters. Delong test was used to compared differences between different AUCs. Results:Of 35 GIST patients, 11(31.4%) were ring-shaped uptake and 24(68.6%) were other uptake patterns, and the differences of necrosis (7/11 vs 12.5%(3/24); P=0.004) and NIH classification (11/11 vs 25.0%(6/24); P<0.001) between the two groups were significant. There were significant differences of metabolic parameters between different groups of tumor diameter, mitotic count, necrosis, image feature, NIH classification ( z values: from -4.70 to -2.09, all P<0.05), while there were no significant differences of Ki-67 ( z values: from -0.83 to -0.71, all P>0.05). Metabolic parameters were correlated with mitotic count, tumor diameter, necrosis, image feature and NIH classification ( rs values: 0.36-0.81, all P<0.05), while was not correlated with Ki-67 ( rs values: 0.12-0.14, all P>0.05). The differences of AUCs between SUV max and MTV 2.5, TLG 2.5, TLG 40%, TLG 50%were significant (0.752, 0.856, 0.856, 0.882, 0.886; z values: 1.96-2.12, all P<0.05). Conclusions:The NIH classification of GIST with ring-shaped uptake on 18F-FDG PET/CT is higher and more prone to necrosis. The 18F-FDG PET/CT metabolic parameters based on different thresholds of SUV max have certain significance for the prediction of NIH classification of GIST, and may be superior to SUV max.

Value of endoscopic ultrasound elastography versus contrast-enhanced computed tomography in the diagnosis of gastrointestinal stromal tumors / 中国基层医药

Objective:To investigate the clinical value of endoscopic ultrasound elastography versus contrast-enhanced computed tomography in the risk stratification of gastrointestinal stromal tumors (GISTs). Methods:Clinical and imaging data were obtained from 77 patients who were confirmed to have GISTs and underwent endoscopic or surgical treatment at Wenzhou Central Hospital between May 2019 and April 2021. Endoscopic ultrasound elastography based on a five-point scoring system and hypotonic gastrointestinal contrast-enhanced computed tomography were performed for preoperative risk stratification of GISTs. The two techniques were compared in terms of the accuracy of preoperative risk stratification of GISTs. The imaging features of the two techniques were summarized.Results:According to the postoperative pathological results, 13 patients were at high risk, 13 patients were at medium risk, 35 patients were at low risk, and 16 patients were at extremely low risk. These patients were divided into two groups according to postoperative pathological results: a low-risk group (low risk + extremely low risk) and a medium- and high-risk group (high + medium risk). In the low-risk group ( n = 51), 42 patients were identified by endoscopic ultrasound elastography to have low-risk GISTs and were recommended to receive endoscopic treatment, while the rest 9 patients were identified to have medium-risk GISTs. Contrast-enhanced computed tomography findings revealed that 30 patients had low-risk GISTs and were recommended to receive endoscopic treatment, and 21 patients had medium-risk GISTs. In the medium- and high-risk group ( n = 26), 4 patients were identified by endoscopic ultrasound elastography to have low-risk GISTs, and 22 patients had medium- or high-risk GISTs. Contrast-enhanced computed tomography findings revealed that 9 patients were identified to have low-risk GISTs, and 17 patients had medium- or high-risk GISTs. Endoscopic ultrasound elastography yielded an overall diagnostic accuracy of 83.11% (64/77), while contrast-enhanced computed tomography had an overall diagnostic accuracy of 61.04% (47/77). Endoscopic ultrasound elastography outperformed contrast-enhanced computed tomography in accurate risk stratification of GISTs ( χ2 = 4.66, P < 0.05). In terms of predicting high-risk GISTs, endoscopic ultrasound elastography had a sensitivity of 84.62% and a specificity of 82.35%, both were higher than those of contrast-enhanced computed tomography (sensitivity: 65.38%; specificity: 58.82%), but the differences in sensitivity and specificity between the two techniques were not significant (sensitivity: Fisher's exact test P = 0.590, specificity: χ2 = 0.93, P > 0.05). Conclusion:Endoscopic ultrasound elastography appears to have a better overall diagnostic accuracy in the risk stratification of GISTs compared with contrast-enhanced computed tomography. The combined use of these two techniques may offer a better comprehensive understanding of the perilesional structure and organ involvements and distant metastasis than a single technique, thereby providing a reliable reference for the choice of treatment for GISTs.

Hallazgo Incidental de Tumor Estromal Gastrointestinal en Divertículo de Meckel. Caso Clínico

Introducción: El divertículo de Meckel es un defecto sacular ubicado en el íleon distal, con una tasa de complicaciones de 4%. La resección quirúrgica está indicada en estas complicaciones, siendo controversial en casos asintomáticos o incidentales. Dentro de las complicaciones existen tumores como los estromales gastrointestinales (GIST). Caso Clínico: Hombre de 57 años, postrado por múltiples factores, presenta úlcera por presión sacra grado IV sobreinfectada y con evolución tórpida. Se decide realizar colostomía terminal, evidenciando un divertículo de Meckel en el intraoperatorio con aspecto sospechoso, por lo cual se decide resecar, resultando en un GIST de bajo riesgo. Se mantiene en seguimiento por 6 meses, sin recidiva tumoral. Discusión: Mientras que la cirugía pareciera ser imperativa en complicaciones, aún existe debate respecto a las indicaciones de resección de divertículo de Meckel hallado incidentalmente en el intraoperatorio por cirugía de otra causa. Si bien puede aumentar la morbimortalidad, la resección estaría indicada según ciertas características como edad, sexo, tamaño y aspecto, dado el riesgo de desarrollo de complicaciones y neoplasias.

Introduction: Meckel's diverticulum is a saccular defect located in the distal ileum, with a complication rate of 4%. Surgical resection is indicated when these complications occur, yet resection in asymptomatic or incidental cases remains controversial. Among these complications, the appearance of tumors such as gastrointestinal stromal (GIST), may occur. Case Report: A 57-year-old male, bedridden due to multi- ple factors, presents with a complicated grade IV sacral pressure ulcer with a torpid evolution. An end colostomy is performed, evidencing a suspicious-looking Meckel's diverticulum intraoperatively, which was resected and resulted to be a low-risk GIST. At a 6-month follow-up, the patient showed no evidence of tumor recurrence. Discussion: While surgery seems to be imperative in complications, there is still a debate regarding the indications for resection of Meckel's diverticulum found incidentally intraoperatively due to surgery for another cause. Although it could increase morbidity and mortality, resection could be indicated according to certain characteristics such as age, sex, size and appearance, given the risk of developing complications and neoplasm.

Tumor de ovario de los cordones sexuales con túbulos anulares: reporte de caso y revisión de la literatura / Ovarian sex cord tumor with annular tubules: case report and review of the literature

RESUMEN Objetivos: Reportar un caso de Tumor de Ovario de los Cordones Sexuales con Túbulos Anulares (TCSTA), hacer una revisión de la literatura acerca del diagnóstico, tratamiento y pronóstico de esta condición. Materiales y métodos: Se informa el caso de una mujer que consultó al Instituto Nacional de Cancerología, Bogotá (Colombia), con diagnóstico final de TCSTA avanzado, quien recibió tratamiento quirúrgico y quimioterapia con evolución satisfactoria a los 6 meses. Se realizó una búsqueda de la literatura en las bases de datos Medline vía PubMed, LILACS y Scielo, que incluía reportes y series de caso de mujeres con diagnóstico de TCSTA, publicados desde 1990, sin incluir rango de edad. Se extrajo información sobre el diagnóstico, tratamiento y pronóstico reportado. Se realizó resumen narrativo de los hallazgos. Resultados: Se incluyeron 14 publicaciones que incluían 26 pacientes. La edad media al diagnóstico fue de 22,5 años. Los síntomas principales fueron alteraciones de la menstruación y dolor pélvico. La tomografía computarizada fue la tecnología de imágenes más frecuentemente utilizada. El tratamiento fue quirúrgico, siempre usado, acompañado de quimioterapia (29 %); 2 casos recibieron radioterapia. Hubo recaída en el 20 % de los casos. La mortalidad fue del 12,5 %, toda en el primer año. Conclusiones: La información sobre la utilidad diagnóstica de las imágenes, marcadores tumorales y estudios de histoquímica es escasa, como también los datos sobre el pronóstico de la entidad. El tratamiento quirúrgico es el de elección, teniendo en cuenta el deseo de fertilidad de la paciente y el estadio tumoral. Se requieren más estudios que documenten de manera más detallada el manejo de esta condición.

ABSTRACT Objectives: To report a case of ovarian sex cord tumor with annular tubules (SCTAT) and conduct a literature review on diagnosis, treatment and prognosis of this condition. Material and methods: Case report of a woman with a final diagnosis of advanced SCTAT seen at the National Cancer Institute in Bogota (Colombia) who received surgical treatment and chemotherapy with a satisfactory course after 6 months. A literature search was conducted in the Medline via PubMed, LILACS and Scielo databases, including case reports and series of women diagnosed with SCTAT published since 1990, not using age ranges. Information about diagnosis, treatment and reported prognosis was retrieved. A narrative summary of the findings was prepared. Results: Fourteen publications with 26 patients were included. Mean age at diagnosis was 22.5 years. The main symptoms were menstruation abnormalities and pelvic pain. Computed tomography (CT) was the imaging technology most frequently used. Surgical treatment was used in all cases, together with chemotherapy in 29 %; 2 patients received radiotherapy. Recurrence occurred in 20 % of cases. Mortality was 12.5 %, with all deaths occurring within the first year. Conclusions: There is a paucity of information about the diagnostic utility of imaging, tumor markers and histochemical studies, as well as prognosis of this disease condition. Surgery is the treatment of choice, taking into consideration the patient's wishes regarding fertility, as well as the stage of the tumor. Further studies are needed to provide more detailed information about this condition.

Gist sincrónico con adenomioma gástrico: Reporte de caso y revisión de la literatura / Synchronous gist with gastric adenomyoma: Case report and literature review

Introducción: La colisión de dos tumores de diferente estirpe celular en un mismo órgano es infrecuente; a pesar de las asociaciones descritas en la literatura, el hallazgo de GIST con adenomioma en sincronismo, llama aún más la atención debido a sus distintos orígenes celulares. Reporte de caso: Presentamos el caso de una paciente mujer de 57 años de edad, quien es sometida a cirugía de resección doble en cuña, y distintos exámenes incluido el anátomo-patológico. Conclusión: Se demuestra la presencia de tumores sincrónicos, GIST gástrico y adenomioma gástrico, a pesar de la infrecuencia de este hallazgo.

Background:The collision of two tumors of different cell lines in the same organ is infrequent; even though, the associations described in the literature, the finding of synchronous GISTwith adenomyoma draws even more attention due to its different cellular origins. We present the case of a 57-year-Case report:old female patient who underwent double wedge resection surgery and various examinations, including pathology. Conclusion:The presence of synchronous tumors, gastric GIST and gastric adenomyoma is demonstrated,despite the infrequency of this finding.

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)

Nódulo del estroma endometrial: Reporte de un caso infrecuente / Endometrial stromal nodule: A rare case report

Introducción: Los tumores del estroma endometrial representan menos del 2% de los tumores uterinos, estando dentro de las neoplasias menos comunes del cuerpo uterino. Se pueden dividir en cuatro categorías principales: nódulo del estroma endometrial, sarcoma del estroma endometrial de bajo grado, sarcoma del estroma endometrial de alto grado y sarcoma uterino indiferenciado. En el presente trabajo se describe el caso de un paciente con diagnóstico de nódulo del estroma endometrial. Caso clínico : Paciente femenino de 50 años de edad, quien refiere inicio de enfermedad en marzo de 2022, caracterizado por presentar sangrado uterino anormal anemizante y aumento de volumen abdominal, por lo que acude a facultativo foráneo, donde indican paraclínicos. Para el día 12 de julio de 2022, presentó dolor abdominal de aparición brusca de moderada a severa intensidad. Motivo por el cual acudió a nuestro centro. Se determina anemia y leucocitosis. Estudios de imagen reportan masa voluminosa, densidad mixta, bien delimitada. Otra lesión hiperecogénica, que corresponde a quiste unicameral de ovario derecho. Se decide resolución quirúrgica, mediante la realización de laparotomía exploradora más protocolo de endometrio, con evolución satisfactoria de la paciente. Conclusión : La histerectomía es el tratamiento de elección. El estudio anatomopatológico es fundamental para su diagnóstico final y diferenciación de los sarcomas estromales, ya que su pronóstico, tratamiento y seguimiento es diferente(AU)

Introduction: Endometrial stromal tumors represent less than 2% of uterine tumors, being among the least common neoplasms of the uterine body. They can be divided into four main categories: endometrial stromal nodule, low-grade endometrial stromal sarcoma, high-grade endometrial stromal sarcoma and undifferentiated uterine sarcoma. This paper describes the case of a patient with a diagnosis of endometrial stromal nodule.Clinical case : A 50-year-old female patient, who reported the onset of the disease in March 2022, characterized by abnormal uterine bleeding with anemia and increased abdominal volume, for which she went to a foreign physician, where they indicated paraclinical tests. On July 12, 2022, he presented abdominal pain of sudden onset of moderate to severe intensity. Which is why she came to our center. Anemia and leukocytosis are determined. Imaging studies report a voluminous mass, mixed density, well delimited. Another hyperechoic lesion, which corresponds to a unicameral cyst of the right ovary. Surgical resolution was decided by performing an exploratory laparotomy and endometrial protocol, with satisfactory evolution of the patient.Conclusion : Hysterectomy is the treatment of choice. The anatomopathological study is fundamental for its final diagnosis and differentiation of stromal sarcomas, since its prognosis, treatment and follow-up are different(AU)

Gastrointestinal stromal tumor: outcomes of the past decade in a reference institution in southern brazil / Tumor estromal gastrointestinal (gist): resultados da última década em uma instituição de referência no sul do brasil

ABSTRACT - BACKGROUND: Gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm of the digestive tract and has a wide variation in biological behavior; surgical resection remains the main form of treatment. AIM: This study aimed to analyze clinicopathological characteristics and survival of patients with GIST in a reference institution for oncological diseases. METHODS: An observational, longitudinal, and retrospective study of patients diagnosed with GIST from January 2011 to January 2020 was carried out by analyzing epidemiological and clinical variables, staging, surgical resection, recurrence, use of imatinib, and curves of overall survival (OS) and disease-free survival (DFS). RESULTS: A total of 38 patients were included. The majority (58%) of patients were males and the median age was 62 years. The primary organs that were affected by this tumor were stomach (63%) and small intestine (17%). Notably, 24% of patients had metastatic disease at diagnosis; 76% of patients received surgical treatment and 13% received neoadjuvant treatment; and 47% of patients received imatinib as adjuvant or palliative therapy. Tumor recurrence was 13%, being more common in the liver. The 5-year OS was 72.5% and DFS was 47.1%. The operated ones had better OS (87.1% vs. 18.5%) and DFS (57.1% vs. 14.3%) in 5 years. Tumor size ≥5 cm had no difference in OS at 5 years, but DFS was 24.6%, when compared with 92.3% of smaller tumors. Patients who were undergoing neoadjuvant therapy and/or using imatinib did not show any significant differences. CONCLUSIONS: Surgical treatment with adequate margins allows the best gain in survival, and the use of imatinib in more advanced cases has prognostic equity with less advanced-stage tumors. Treatment of metastatic tumors seems promising, requiring further studies.

RESUMO - RACIONAL: O Tumor estromal gastrointestinal (Gastrointestinal stromal tumor - GIST) é a neoplasia mesenquimal mais comum do trato digestivo, possui comportamento biológico variado e a principal forma de tratamento é a ressecção cirúrgica. OBJETIVO: analisar as características clínico-patológicas e a sobrevida de pacientes com GIST em uma instituição de referência para doenças oncológicas. MÉTODOS: Foi realizado um estudo observacional, longitudinal e retrospectivo de pacientes com diagnóstico de GIST de janeiro de 2011 a janeiro de 2020, analisando variáveis epidemiológicas e clínicas, estadiamento, ressecção cirúrgica, recidiva, uso de imatinibe e curvas de sobrevida global (SG) e sobrevida livre de doença (SLD). RESULTADOS: foram incluídos 38 pacientes, a maioria (58%) do sexo masculino, idade mediana de 62 anos. Os principais órgãos primários foram estômago (63%) e intestino delgado (17%). 24% tinham doença metastática ao diagnóstico. 76% receberam tratamento cirúrgico e 13% tratamento neoadjuvante. 47% dos pacientes receberam Imatinib como terapia adjuvante ou paliativa. A recorrência tumoral foi de 13%, mais comum no fígado. SG de 5 anos foi de 72,5% e SLD 47,1%. Os operados tiveram melhor SG (87,1% vs. 18,5%) e SLD (57,1% vs. 14,3%) em 5 anos. O tamanho do tumor igual ou maior que 5 cm não teve diferença na SG em 5 anos, mas SLD foi de 24,6%, em comparação com 92,3% dos tumores menores. Pacientes em terapia neoadjuvante e/ou em uso de imatinibe não apresentaram diferenças significativas. CONCLUSÕES: O tratamento cirúrgico com margens adequadas permite o melhor ganho de sobrevida, e o uso de Imatinibe em casos mais avançados tem equidade prognóstica com tumores em estágio menos avançado. O tratamento de tumores metastáticos parece promissor, necessitando de mais estudos.

Laparoscopic versus open surgery in gastric gastrointestinal stromal tumors larger than 5 cm: a systematic review and meta-analysis / Abordagem laparoscópica versus cirurgia aberta em tumores estromais gástricos superiores a 5 cm: revisão sistemática e meta-análise

ABSTRACT BACKGROUND: Surgical resection represents the main treatment for resectable nonmetastatic gastric gastrointestinal stromal tumors. Despite the feasibility and safety of laparoscopic resection, its standard use in gastric tumors larger than 5 cm is yet to be established. AIMS: This study aimed to compare the current evidence on laparoscopic resection with the classical open surgical approach in terms of perioperative, postoperative, and oncological outcomes. METHODS: The PubMed, Scopus, and Web of Science databases were consulted. Articles comparing the approach to gastric gastric gastrointestinal stromal tumors larger than 5 cm by open and laparoscopic surgery were eligible. A post hoc subgroup analysis based on the extent of the surgery was performed to evaluate the operative time, blood loss, and length of hospital stay. RESULTS: A total of nine studies met the eligibility criteria. In the study, 246 patients undergoing laparoscopic surgery and 301 patients undergoing open surgery were included. The laparoscopic approach had statistically significant lower intraoperative blood loss (p=0.01) and time to oral intake (p<0.01), time to first flatus (p<0.01), and length of hospital stay (0.01), compared to the open surgery approach. No significant differences were found when operative time (0.25), postoperative complications (0.08), R0 resection (0.76), and recurrence rate (0.09) were evaluated. The comparative subgroup analysis between studies could not explain the substantial heterogeneity obtained in the respective outcomes. CONCLUSION: The laparoscopic approach in gastric gastrointestinal stromal tumors larger than 5 cm compared to the open surgical approach is a technically safe and feasible surgical method with similar oncological results.

RESUMO RACIONAL: A resseção cirúrgica representa a principal forma de tratamento de tumores estromais gástricos não metastáticos ressecáveis. Apesar da viabilidade e segurança da ressecção laparoscópica, a sua utilização generalizada em tumores gástricos com mais de 5 centímetros ainda não foi estabelecida. OBJETIVOS: Comparar as evidências atuais sobre a resseção por via laparoscópica com a cirurgia aberta, em termos de resultados peri-, pós-operatórios e oncológicos. MÉTODOS: Foram consultadas as bases de dados PubMed, Scopus e Web of Science. Artigos que comparassem a abordagem de tumores estromais gástricos gástricos com tamanho superior a 5 centímetros por cirurgia aberta e por via laparoscópica foram incluídos. Uma análise de subgrupos post-hoc, com base na extensão da cirurgia, foi realizada para os outcomes tempo intra-operatório, perdas de sangue e tempo de hospitalização. RESULTADOS: Nove estudos cumpriram os critérios de elegibilidade, tendo sido incluídos 246 pacientes submetidos a cirurgia por via laparoscópica e 301 pacientes submetidos a cirurgia aberta. A abordagem laparoscópica apresentou perdas de sangue intra-operatórias (p=0,01) e tempos até alimentação oral (p<0,01), para primeiro flato (p<0,01) e de hospitalização (0,01) estatisticamente inferiores relativamente à abordagem por cirurgia aberta. Não foram encontradas diferenças significativas quando avaliados o tempo operatório (0,25), complicações pós-operatórias (0,08), resseção R0 (0,76) e taxa de recorrência (0,09). A análise de subgrupos comparativa não permitiu explicar a heterogeneidade substancial obtida nos respetivos outcomes. CONCLUSÕES: A via laparoscópica em tumores estromais gástricos superiores a 5 centímetros comparativamente com a abordagem por cirurgia aberta, constitui um método cirúrgico tecnicamente seguro e viável, com resultados oncológicos semelhantes.

Calcifying fibrous tumor

ABSTRACT Calcifying fibrous tumor is a rare benign mesenchymal neoplasm. The etiology and pathogenesis of this tumor are uncertain. It has wide anatomical distribution. The tumor is most commonly found in the soft tissues of the extremities in younger individuals. However, in middle-aged patients, it tends to affect the visceral locations more commonly. In visceral location, it can mimic aggressive lesions clinically. The purpose of this report is to describe a case of calcifying fibrous tumor in a 71-year-old female with a history of breast carcinoma who was found to have an incidental small bowel mass on her follow-up. Clinically and radiologically, the mass was suspicious for either metastatic disease or gastrointestinal stromal tumor. The patient underwent open small bowel resection, and a 6.5 cm segment of the small bowel was sent to pathology. Grossly, a 2.0 cm tan-pink smooth round submucosal polyploid mass protruding into the lumen, mimicking a gastrointestinal stromal tumor, was identified. The tumor was hard and serially sectioned to reveal a white, calcified cut surface. Microscopically, the tumor appeared hypocellular and composed of scant spindle cells embedded in a dense, hyalinized and calcified collagenous stroma. Immunohistochemical stains for pan-cytokeratin, DOG1, desmin, S100, CD34, and MUC4 were negative, and a diagnosis of the calcifying fibrous tumor was rendered. This case provides a rare gross specimen image of calcifying fibrous tumor and highlights the importance of knowledge of rare entities in providing an accurate diagnosis for entities that can mimic other lesions.

Efficacy of endoscopic ligation resection and endoscopic submucosal excavation for small gastrointestinal stromal tumors originating from muscularis propria / 中华消化内镜杂志

Clinical data of 43 patients who underwent endoscopic resection for gastrointestinal stromal tumors (GIST) of length ≤1.2 cm at the Digestive Endoscopy Center of the 909th Hospital from January 2016 to December 2018 were retrospectively analyzed. The patients were divided into the endoscopic ligation resection (ELR) group ( n=27) and the endoscopic submucosal excavation (ESE) group ( n=16). The general, perioperative and follow-up data of the two groups were compared. The results showed that there was no significant difference in the general data between the two groups. The operation time was 20.0 (18.0,25.0) min in the ELR group and 27.5 (23.0,37.5) min in the ESE group, showing significant difference ( U=92.5, P=0.001). The en bloc resection rates were 100.0% (27/27) in the ELR group and 81.3% (13/16) in the ESE group, showing significant difference ( P=0.045). The postoperative hospital stays were 3 (2,4) days in the ELR group and 5 (4,6) days in the ESE group, showing significant difference ( U=125.5, P=0.020). There was no significant difference in the intraoperative bleeding rate, intraoperative hemorrhage volume, intraoperative perforation rate, number of hemostatic clips or postoperative complications including hemorrhage, fever and peritonitis between the two groups ( P>0.05). During the follow-up, there was no recurrence or metastasis of GIST in both groups. ELR and ESE can be safe and effective for small GIST ≤1.2 cm in diameter. Compared with the ESE group, the operation time and postoperative hospital stay are shorter with higher en bloc resection rate in the ELR group.

Analysis of clinicopathological features, gene mutation characteristics and prognosis of 228 cases of primary gastrointestinal stromal tumor of small intestine / 中华消化杂志

Objective:To analyze the clinicopathological features, gene mutation characteristics, and prognostic related factors of patients with primary gastrointestinal stromal tumor (GIST) of small intestine.Methods:From January 1, 2011 to December 30, 2019, surgical resected and pathological diagnosed small intestinal GIST without preoperative adjuvant therapy, at Tianjin Medical University Cancer Institute & Hospital were retrospectively collected. The mutational status of KIT exons 9, 11, 13, and 17 and platelet-derived growth factor receptor alpha ( PDGFRA) exons 12 and 18 were detected by polymerase chain reaction and Sanger direct sequencing. Clinicopathological features and gene mutation characteristics were analyzed. Pearson chi-square test and Bonferroni continuous correction test were used to compare the categorical variables among groups. Kaplan-Meier method and log-rank test were used for univariate survival analysis. The multivariate Cox proportional hazards regression model was used for multivariate survival analysis. Results:The proportions of patients with maximum tumor diameter> 10.0 cm and high-risk GIST located in the jejunum and ileum were higher than those of patients with primary GIST located in the duodenum (18.7%, 28/150 vs. 6.4%, 5/78; 56.7%, 85/150 vs. 43.6%, 34/78), and the differences were statistically significant ( χ2=14.67 and 12.46, P=0.002 and 0.006). The results of gene detection of 58 cases of small intestinal GIST indicated that the percentage of KIT gene mutant and wild type accounted for 84.5% (49/58) and 15.5% (9/58), among which 34 cases (69.4%), 12 cases (24.5%), 2 cases (4.1%) and 1 case (2.0%) were KIT gene exons 11, 9, 13 and 17 mutations, respectively, and none of the case with PDGFRA mutation. The 3-, 5-, and 10-year progression-free survival rates of the patients with small intestinal GIST were 88.1%, 85.0%, and 68.3%, respectively, and the 3-, 5-, and 10-year overall survival rates were 96.6%, 94.5%, and 86.1%, respectively. The results of univariate survival analysis showed that the progression-free survival rate and overall survival rate of patients with very low-risk and low-risk GIST were higher than those of patients with intermediate-risk and high-risk GIST (100.0%, 49/49 vs. 72.3%, 81/112; 100.0%, 49/49 vs. 89.3%, 100/112, respectively), and the differences were statistically significant ( χ2=14.07 and 4.92, P<0.001、=0.027). The results of univariate survival analysis of patients with intermediate-risk and high-risk GIST showed that the epithelioid cell type, mitotic index >5/5 mm 2, Ki-67 proliferation index >5%, and without postoperative adjuvant therapy were all related with progression-free survival time, and the differences were statistically significant ( χ2=8.39, 5.53, 13.73 and 15.44, P=0.004、0.019、<0.001、<0.001). Without postoperative adjuvant therapy was related with poor overall survival time ( χ2=7.06, P=0.008). The results of univariate analysis in patients with intermediate-risk and high-risk GIST and without postoperative adjuvant therapy showed that the epithelioid cell type, high-risk, mitotic index >5/5 mm 2 and Ki-67 proliferation index >10% were all related with progression-free survival time, and the differences were statistically significant ( χ2=10.08, 6.51, 10.37 and 15.72, P=0.001、0.011、0.001、<0.001). The results of multivariate analysis indicated that Ki-67 proliferation index >5% ( HR=5.018, 95% confidence interval(95% CI) 1.745 to 14.430, P=0.003) and without postoperative adjuvant treatment ( HR=0.145, 95% CI 0.051 to 0.414, P<0.001) were independent risk factors of postoperative tumor progression in patients with small intestinal intermediate-risk and high-risk GIST. Ki-67 proliferation index>10% ( HR=8.381, 95% CI 1.364 to 51.487, P=0.022) was an independent risk factor of postoperative tumor progression in patients with small intestinal intermediate-risk and high-risk GIST and without postoperative adjuvant treatment. Conclusions:The most common mutation in small intestinal primary GIST is KIT mutation, followed by wild type, no case of PDGFRA gene mutation has been found. High Ki-67 proliferation index can predict poor prognosis of patients with moderate-risk and high-risk small intestinal primary GIST. Postoperative adjuvant therapy can significantly improve the prognosis of patients with small intestinal intermediate-risk and high-risk primary GIST.