Research progress in pharmacokinetics and therapeutic drug monitoring of tyrosine kinase inhibitors in the treatment of gastrointestinal stromal tumors / 中国药房

Tyrosine kinase inhibitors （TKIs） represent a class of small-molecule targeted drugs that improve the survival time of patients with gastrointestinal stromal tumor （GIST）. Imatinib， sunitinib， regorafenib， ripretinib， and avapritinib are commonly used TKIs in the clinical treatment of various types of GIST. This article provides a comprehensive review of the pharmacokinetics and therapeutic drug monitoring （TDM） of these five drugs， finding that there is significant individual variability in the pharmacokinetics of these drugs. Among them， the absorption of imatinib， regorafenib， and avapritinib are influenced by food intake. Imatinib should be taken with meals and 200 mL of water， regorafenib is taken with a low-fat meal， while avapritinib is taken on an empty stomach. TKIs are mainly metabolized by cytochrome P450 3A4 （CYP3A4）， and when used in combination with CYP3A4 inducers or inhibitors， drug exposure levels will significantly change； apart from metabolic enzymes， the exposure levels of TKIs are also influenced by interactions with the transporter proteins P-glycoprotein and breast cancer resistance protein. Currently， research on TDM for TKIs is still in the exploratory stage， with a substantial amount of literature reporting the effective concentrations of imatinib， sunitinib and regorafenib. However， the precise relationship between exposure levels and efficacy/ toxicity needs further exploration. Currently， there is a lack of research on the correlation between exposure levels and efficacy/ toxicity of ripretinib and avapritinib. It is recommended to implement TDM in patients taking these drugs and explore their therapeutic window in combination with pharmacokinetic models. The commonly used methods for clinical TDM of TKIs include immunoassay， chromatography， and surface-enhanced Raman spectroscopy， providing a technical basis for clarifying the therapeutic window of TKIs.

Consensus of Chinese experts on individualized medication management of imatinib for gastrointestinal stromal tumors / 中国药房

@#OBJECTIVE To provide reference for guiding the individualized drug therapy management of imatinib for gastrointestinal stromal tumor （GIST）， with the goal of enhancing patient survival rates and improving their quality of life. METHODS Using a nominal group technique， a multidisciplinary （clinical， pharmaceutical and evidence-based） expert panel was formed to create the Consensus of Chinese Experts on Individualized Medication Management of Imatinib for Gastrointestinal Stromal Tumors outline through joint discussions. The expert panel conducted systematic retrieval， analysis， and summarization of the outline’s content， and reached relevant consensus based on China’s current situation， clinical needs， and research evidence. An external expert panel was also formed， comprising experienced multidisciplinary experts in clinical practice. Delphi method questionnaire was employed to openly collect the external experts’ opinions， which were then organized， summarized， analyzed， provided with feedback， revised， and finally formed into a consensus. RESULTS & CONCLUSIONS The drafting of this consensus included the clinical application of imatinib in neoadjuvant therapy for GIST patients， adjuvant therapy for adult patients with significant risk of recurrence after surgical resection， and drug therapy for patients with recurrent， metastatic， or unresectable tumors； pharmaceutical monitoring and long-term medication management. This consensus provides standardized processes and methods for medical institutions in individualized drug therapy management for GIST patients and holds significant importance in improving the clinical efficacy of imatinib and ensuring drug safety.

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.

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.

Succinate dehydrogenase inhibitors fungicides: a review of their impact on human health and epigenetic changes / Fungicidas inibidores da succinato desidrogenase: uma revisao de seu impacto na saúde humana e alterares epigenéticas / Fungicidas inhibidores de la succinato deshidrogenasa: una revisión de su impacto en la salud humana y los cambios epigenéticos

Abstract Succinate dehydrogenase inhibitors (SDHIs), fungicides currently most used in agriculture in Brazil, act by blocking the enzyme succinate dehydrogenase (SDH) from plant pathogens. However, studies show that SDHIs can not only inhibit SDH activity in target fungi, but also block that activity in human cells. Considering the medical and agricultural implications of SDH, the purpose of this narrative review is to describe the relationship between exposure to fungicides SDHIs and epigenetic regulation of SDH associated with the development of gastrointestinal stromal tumor, pheochromocytoma/paraganglioma, and cancer. The results obtained with the research showed that the human SDH enzyme exhibited sensitivity to some tested SDHIs, which may cause microcephaly and defects in neurological development. Deficiency of SDH activity causes accumulation of succinate which can act as an oncometabolite inhibit-ing iron-dependent dioxygenases and alpha-ketoglutarate, eleven translocation -TET and histone demethylases, inducing epigenetic changes that lead to multiple cancers and other diseases. Therefore, further in vitro and in vivo analyzes should be performed to assess susceptibility to diseases influenced by the toxic effect of SDHIs.

Resumo Os inibidores da succinato desidrogenase (SDHIs), fungicidas atualmente mais utilizados na agricultura no Brasil, atuam bloqueando a enzima succinato desidrogenase (SDH) de fitopatógenos. No entanto, estudos mostram que SDHIs podem nao apenas inibir a atividade de SDH em fungos alvo, mas também bloquear essa atividade em células humanas. Considerando as implicares médicas e agrícolas do SDH, o objetivo desta revisao narrativa é descrever a relaqao entre a exposiqao a fungicidas SDHIs e a regulaqao epigenética do SDH associada ao desenvolvimento de tumor estromal gastrointestinal, feocromocitoma/paraganglioma e cáncer. Os resultados obtidos com a pesquisa mostraram que a enzima SDH humana apresentou sensibilidade a alguns SDHIs testados, que podem causar microcefalia e defeitos no desenvolvimento neurológico. A deficiencia da atividade da SDH causa acumulo de succinato que pode atuar como um oncometabólito inibindo as dioxigenases dependentes de ferro e alfa-cetoglutarato, onze translocaqóes -TET e histonas desmetilases, induzindo alteraqóes epigenéticas que levam a múltiplos canceres e outras doenqas. Portanto, análises adicionais in vitro e in vivo devem ser realizadas para avaliar a suscetibilidade a doenqas influenciadas pelo efeito tóxico dos SDHIs.

Resumen Los inhibidores de la succinato deshidrogenasa (SDHI), los fungicidas actualmente más utilizados en la agricultura en Brasil, actúan bloqueando la enzima succinato deshidrogenasa (SDH) de los patógenos de las plantas. Sin embargo, los estudios muestran que los SDHI no solo pueden inhibir la actividad de SDH en los hongos objetivo, sino que también bloquean esa actividad en las células humanas. Teniendo en cuenta las implicaciones médicas y agrícolas de SDH, el propósito de esta revisión narrativa es describir la relación entre la exposición a fungicidas SDHI y la regulación epigenética de SDH asociada con el desarrollo de tumores del estro-ma gastrointestinal, feocromocitoma/paraganglioma y cáncer. Los resultados obtenidos con la investigación mostraron que la enzima SDH humana mostró sensibilidad a algunos SDHI probados, lo que puede causar microcefalia y defectos en el desarrollo neurológico. La deficiencia de la actividad de SDH provoca la acumulación de succinato que puede actuar como un oncometabolito que inhibe las dioxigenasas dependientes de hierro y el alfa-cetoglutarato, once translocaciones -TET e histona desmetilasas, induciendo cambios epigenéticos que conducen a múltiples cánceres y otras enfermedades. Por lo tanto, se deben realizar más análisis in vitro e in vivo para evaluar la susceptibilidad a enfermedades influenciadas por el efecto tóxico de los SDHI.

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).

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.

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.

Efficacy of different laparoscopic surgeries for gastrointestinal stromal tumors of gastric cardia and fundus: a multicenter study / 中华消化外科杂志

Objective:To investigate the efficacy of different laparoscopic surgeries for gastrointestinal stromal tumors (GIST) of gastric cardia and fundus.Methods:The retrospective cohort study was conducted. The clinicopathological data of 251 patients with GIST of gastric cardia and fundus who underwent laparoscopic radical resection in 14 medical centers, including Guangdong Provincial People′s Hospital et al, from December 2007 to December 2021 were collected. There were 123 males and 128 females, aged 58(24,87)years. Observation indicators: (1) treatment; (2) clinicopathological data of patients undergoing different laparoscopic surgeries; (3) subgroup analysis for special laparoscopic techniques. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test or ANOVA. Measure-ment data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test or Kruskal-Wallis H test. Count data were described as absolute numbers or percentages. Comparison of ordinal data was conducted using the rank sum test. Results:(1) Treatment. Of the 251 patients,202 cases underwent gastric wedge resection, 26 cases underwent special laparoscopic techniques including 10 cases with serotomy and dissection and 16 cases with transluminal gastrectomy, 23 cases underwent structural gastrectomy including 6 cases with total gastrectomy and 17 cases with proximal partial gastrectomy. There were 24 patients had postoperative complications after surgery. (2) Clinicopathological data of patients undergoing different laparoscopic surgeries. The gender (male, female), age, tumor diameter, operation time, volume of intraoperative blood loss, length of incision, time to postoperative initial whole liquid food intake, time to postoperative initial semi-liquid food intake, duration of postoperative hospital stay, cases with perioperative complications, cases with mitotic count as ≤5/50 high power field, 6?10/50 high power field, >10/50 high power field, cases be classified as very low risk, low risk, medium risk, high risk according to the National Institutes of Health risk classification, cases with tumor located at fundus and gastric cardia were 93, 109, (59±11)years, 3.50(0.40,10.00)cm, 88.00(25.00,290.00)minutes,20.00(25.00,290.00)mL, 4.00(2.00,12.00)cm, 3.00(1.00,9.00)days, 4.00(1.00,16.00)days, 5.00(1.00,18.00)days, 14, 164, 31, 7, 47, 83, 50, 22, 30, 172 in patients undergoing gastric wedge resection, respectively. The above indicators were 19, 7, (49±14)years, 2.55(0.20,5.00)cm, 101.00(59.00,330.00)minutes, 27.50(2.00,300.00)mL, 4.50(0,6.00)cm, 2.50(1.00,10.00)days, 4.00(1.00,16.00)days, 6.00(1.00,18.00)days, 3, 20, 5, 1, 15, 5, 2, 4, 24, 2 in patients undergoing special laparos-copic techniques, and 11, 12, (52±10)years, 5.00(0.80,10.00)cm, 187.00(80.00,325.00)minutes, 50.00(10.00,300.00)mL, 6.00(4.00,12.00)cm, 4.00(2.00,8.00)days, 6.00(3.00,14.00)days, 8.00(2.00,18.00)days, 7, 11, 5, 7, 2, 6, 6, 9, 13, 10 in patients undergoing structural gastrectomy. There were significant differences in the above indicators among the three groups of patients ( χ2=6.75, F=10.19, H=17.71, 37.50, 35.54, 24.68, 16.09,20.20, 13.76, χ2=13.32, Z=28.98, 32.17, χ2=82.14, P<0.05). (3) Subgroup analysis for special laparoscopic techniques. The time to postoperative initial whole liquid food intake, time to postoperative initial semi-liquid food intake, classification of tumor location (endophytic type, exophytic type, parietal type) were 4.50(1.00,10.00)days, 8.00(3.00,12.00)days, 0, 8, 2 in patients undergoing serotomy and dissection, versus 2.00(1.00,4.00)days, 3.00(1.00,6.00)days, 16, 0, 0 in patients undergoing transluminal gastrectomy. There were significant differences in time to postoperative initial whole liquid food intake, time to postoperative initial semi-liquid food intake between them ( Z=-2.65, -3.16, P<0.05); and there was a significant difference in classification of tumor location between them ( P<0.05). Conclusions:Gastric wedge resection is the most commonly used laparoscopic technique for GIST of gastric cardia and fundus. The application of special laparoscopic techniques is focused on the GIST of cardia to preserve the function of the cardia.

Application of laparoscopic surgery for gastric stromal tumor in unfavorable sites / 国际外科学杂志

Gastrointestinal stromal tumor (GIST) is a kind of mesenchymal tumor, most commonly found in the stomach, with unique immunophenotype and molecular genetic characteristics. Gastric GIST mostly originates from the musculi propria of the stomach wall. It often grows expansively with clear boundaries and is relatively easy to separate. Surgery is still the preferred treatment for gastric GIST. With the rapid development of laparoscopic technique, laparoscopic surgical treatment for gastric GIST has been gradually recognized. However, it still remains unclear whether laparoscopic surgery can be applied in gastric gastrointestinal stromal tumors located in unfavorable sites. Here, this paper will combine author center′s exploration and clinical application on laparoscopic surgery for gastric GIST located in unfavorable sites and make a brief summary in order to choose a better way for treatment of gastric GIST located in unfavorable sites.

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.

Condroma pulmonar y paraganglioma carotídeo como manifestaciones de la tríada de Carney: reporte de un caso / Pulmonary chondroma and carotid paraganglioma as expressions of Carney's triad: report of a case

Resumen Objetivos: Presentar caso clínico y revisión de la literatura sobre asociación de tumores poco frecuentes compatibles con diagnóstico de tríada de Carney. Paciente y Métodos: Revisión de ficha clínica de paciente de sexo femenino de 39 años de edad con antecedentes de asma, quien acude a servicio de urgencias por síntomas respiratorios. En estudio con imágenes se evidencia masa pulmonar en lóbulo superior derecho probablemente hamartoma y masa en la bifurcación carotídea izquierda compatible con posible paraganglioma. Se completó el estudio con endoscopia digestiva alta sin evidencia de tumor gástrico y PET-CT (tomografía de emisión de positrones-tomografía computarizada) que descartó otras lesiones. Resultados: La paciente fue sometida a resección quirúrgica de ambos tumores (pulmonar y carotídeo). En estudio histopatológico diferido, se plantean los diagnósticos de paraganglioma carotideo y hamartoma pulmonar, el cual, luego de una segunda revisión histopatológica, es corregido a condroma pulmonar. Discusión: La tríada de Carney se compone por la asociación de al menos 2 de 3 tumores: tumor estromal gastrointestinal (GIST), paraganglioma extra-adrenal y condroma pulmonar. Su expresión es variable, coexistiendo en forma completa en solo el 22% de los casos. Conclusión: Los pacientes con sospecha de tríada de Carney deben recibir evaluación multidisciplinaria, estudio completo en búsqueda de tumores asociados y seguimiento a largo plazo por posibles recurrencias o metástasis.

Objective: To present a clinical case and review of the literature on the infrequent association of pulmonary and extra thoracic tumors compatible with Carney's triad. Patient and Methods: Review of clinical records of a 39 years-old female patient with history of asthma who presented in the emergency department with respiratory symptoms. An imaging study showed a pulmonary mass in the right upper lobe with the aspect of hamartoma and a mass in the left carotid artery bifurcation compatible with a possible paraganglioma. Upper gastrointestinal endoscopy showed no evidence of gastric tumor and a PET-CT (Positron Emission Tomography - Computed Tomography) excluded other lesions. Results: Patient underwent surgical resection of both tumors (pulmonary and carotid). Diagnosis of carotid paraganglioma and pulmonary hamartoma were stated by histopathology. However, lung tumor after a second pathological analysis was confirmed to be a pulmonary chondroma. Discussion: Carney's triad is defined by the association of at least 2 of 3 tumors: Gastrointestinal Stromal Tumor (GIST), extraadrenal paraganglioma and pulmonary chondroma. Its expression is variable, coexisting completely in only 22% of cases. Conclusion: Patients with suspected Carney's triad should receive a multidisciplinary assessment, a complete study searching associated tumors and long-term follow-up for recurrences or metastases.

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)

Jejunal GIST — An Obscure Cause of Melaena

Gastrointestinal Stromal Tumours (GISTs) are one of the rare causes of Alimentary Tract Neoplasm. They arise from the Interstitial Cells of Cajal (ICC) with overexpression of proto-oncogenes like KIT, PDGFRA and BRAF-Kinase, etc1. The typical location of these tumors is the stomach with Jejunal GIST being the rarest variant. The maximal incidence of the disease is reported in the sixth decade of life. GISTs are often asymptomatic and clinicians are misdirected towards a different diagnosis because of its variable nature of presentation. The clinical feature typically ranges from non-specific abdominal symptoms like nausea, vomiting, bloating, etc, to abdominal emergencies like hemorrhage, anemia, or obstruction. Although mostly benign, there is a high probability of progression to malignancy2. Thus, in patients with no appreciable cause of gastrointestinal bleed or chronic abdominal discomfort, GIST should have high suspicion index. This can help to limit the progression and thereby prevent further complications. Due to its location, it is difficult to identify by Endoscopy or Colonoscopy. Single Balloon Enteroscopy (SBE) and CT Scan of Abdomen are the primary investigational modalities. The treatment aims at resection of the mass with continued Postsurgical surveillance and targeted molecular therapy in some cases. Herein, we report a 14-year-old boy with chronic paleness and gradual onset repeat episodes of Melaena. Despite repeated blood transfusions, the patient had a Hemoglobin

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.

Update on Diagnosis and Treatment of Gastrointestinal Stromal Tumors / 肿瘤防治研究

In recent years, with the emergence of new research evidence, the domestic and foreign guidelines in the field of gastrointestinal stromal tumors (GISTs) have been updated. The adjusted contents cover almost every link of GISTs management, from GISTs diagnosis, biological behavior, surgical treatment to targeted drug treatment. Since 2020, the NCCN of the United States has separated the contents related to GISTs from the clinical practice guide for soft tissue sarcoma for the first time to form 2021 V.1 versions. The CSCO has also adjusted and upgraded the previous consensus of Chinese experts on the diagnosis and treatment of GISTs to 2020 and 2021 versions of the guidelines for the diagnosis and treatment of GISTs. This opens a new model of accurate diagnosis and treatment of GISTs under the guidance of evidence-based medicine. The listing of new targeted drugs afatinib and ripretinib is expected to get rid of the drug-resistant treatment dilemma of metastatic GISTs, enrich the back-line treatment camp, provide more opportunities for surgical intervention, and then bring survival benefits to patients with advanced GISTs.