A randomized study of 6 vs 3 years of adjuvant imatinib in patients with localized GIST at high risk of relapse.

BACKGROUND: The administration of adjuvant imatinib during three years is indicated after resection of primary localized GIST at high risk of recurrence, but many patients relapse afterwards. METHODS: IMADGIST (NCT02260505) was a multicenter open-label, randomized phase III study evaluating the maintenance of imatinib for 3 more years (6-years arm) compared to Interruption (3-years arm) from the day of randomization, conducted in the French Sarcoma Group. The primary endpoint was intent-to treat disease-free survival (DFS). Secondary endpoints include overall survival, time to imatinib resistance, response after imatinib reintroduction at relapse, safety. RESULTS: From December 24th 2014 to April 4th 2023; 136 patients aged ≥18, ECOG PS ≤2, with a localized GIST with a R0 or R1 surgery, and a risk of tumor recurrence ≥35% according to NCCN risk classification were randomized in 14 centers. Sixty-five patients were randomized to the 3-Years arm vs. 71 in the 6-Years arm. There were 68 males and females. Primary sites were gastric and small bowel in 60 (44%) and 64 (47%) patients respectively. Respectively 52 (38%) and 71 (52%) of patients had a risk of relapse of 35-70% and >70%.. With a median follow-up of 55 (IQR=46-59) months post randomization, DFS was significantly superior in the 6-Years arm (HR: 0.40 [0.20-0.69], p=0.0008). Time to imatinib resistance, survival, adverse events and quality of life are not different in the 2 arms. CONCLUSIONS: Three additional years of adjuvant imatinib reduces the risk of relapse in patients who have received 3 years of adjuvant imatinib with an acceptable tolerance.

Spontaneous haemoperitoneum caused by a bleeding gastric gastrointestinal stromal tumour.

Spontaneous haemoperitoneum is described as a collection of blood in the peritoneal cavity due to non-traumatic aetiology. Common causes in the literature include splenic, hepatic and gynaecological pathology. Patients with spontaneous haemoperitoneum usually present with non-specific dull aching abdominal pain. Spontaneous haemoperitoneum can only be radiologically diagnosed and, if not treated in time, is life threatening. Rupture of a gastrointestinal stromal tumour (GIST) presenting as a spontaneous haemoperitoneum is a rare event. Gastric GIST presents as ambiguous abdominal pain, complications of which include melena, obstruction and rupture. This is a report of a male patient in his early 60s who presented with acute abdominal pain. A contrast-enhanced CT of the abdomen showed haemoperitoneum with an unknown source of origin. Diagnostic laparoscopy showed a bleeding exophytic mass arising from the stomach, which was resected. Thus, early diagnosis with proper imaging and prompt treatment has a favourable outcome.

Usefulness of newer testing modalities for the accurate diagnosis of culture-negative endocarditis.

A woman in her 80s with a history of congestive heart failure, atrial arrhythmia treated with atrioventricular nodal ablation and permanent pacemaker (PPM) placement, mitral valve disease status post-repair and colon cancer status post-treatment was admitted for further evaluation of severe dyspnea on exertion. Imaging revealed vegetation on both the prosthetic mitral valve and the PPM lead. Blood cultures were collected without growth, so a cell-free DNA Karius test was performed, which can detect over 1000 pathogens and has a sensitivity between 87% and 93%. Testing returned positive results for Streptococcus bovis subspecies pasteurianus Given its association with colorectal cancer, abdominal imaging and an endoscopic biopsy were performed, showing recurrent colonic malignancy. The patient underwent a right colon resection prior to cardiac intervention. This report describes the clinical application of the novel cell-free DNA Karius test, which led to the diagnosis of recurrent colon cancer associated with S. pasteurianus endocarditis.

Intracranial metastasis of gastrointestinal stromal tumors: A literature review of published case reports and case presentation.

Background: Intracranial metastasis of gastrointestinal stromal tumors (GISTs) is uncommon and the optimal management for these patients remains undefined. The introduction of selective tyrosine kinase inhibitors (TKI) has drastically improved survival in patients with GISTs. However, its efficacy in patients with intracranial metastasis of GISTs is uncertain due to poor penetration of the blood brain barrier. The role of surgery and radiotherapy in these patients has also not been established. No large-scale studies exist, and the literature is limited to case reports. We report a case treated at our institution, conducted a literature review of existing case reports, and discussed the optimal management of patients with intracranial metastasis of GISTs. Methods: A literature review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. All studies with intracranial metastasis of GISTs were included, with data extracted and analyzed in totality. Results: 26 cases were included in the review. The median time to diagnosis of intracranial metastasis in patients with previously known GISTs was 66 months. Solitary metastasis was seen in 16 cases (59.3 %). 18 patients (69.72 %) underwent surgical resection; 14 had additive therapy with 9 receiving TKI. The mean duration of follow up was 11 months. Clinical response was seen in 3 patients in the non-surgical group, all 3 were treated with TKI alone. Conclusion: The effectiveness of TKI in intracranial GISTs metastasis is seen both as first-line therapy for asymptomatic lesions and as an additive treatment post-surgery. Surgery retains a key role in establishing histological and molecular diagnosis and for symptomatic relief of mass effect.

Fibroblast Growth Factor 2 (FGF2) Activates Vascular Endothelial Growth Factor (VEGF) Signaling in Gastrointestinal Stromal Tumors (GIST): An Autocrine Mechanism Contributing to Imatinib Mesylate (IM) Resistance.

We showed previously that the autocrine activation of the FGFR-mediated pathway in GIST lacking secondary KIT mutations was a result of the inhibition of KIT signaling. We show here that the FGF2/FGFR pathway regulates VEGF-A/VEGFR signaling in IM-resistant GIST cells. Indeed, recombinant FGF2 increased the production of VEGF-A by IM-naive and resistant GIST cells. VEGF-A production was also increased in KIT-inhibited GIST, whereas the neutralization of FGF2 by anti-FGF2 mAb attenuated VEGFR signaling. Of note, BGJ 398, pan FGFR inhibitor, effectively and time-dependently inhibited VEGFR signaling in IM-resistant GIST T-1R cells, thereby revealing the regulatory role of the FGFR pathway in VEGFR signaling for this particular GIST cell line. This also resulted in significant synergy between BGJ 398 and VEGFR inhibitors (i.e., sunitinib and regorafenib) by enhancing their pro-apoptotic and anti-proliferative activities. The high potency of the combined use of VEGFR and FGFR inhibitors in IM-resistant GISTs was revealed by the impressive synergy scores observed for regorafenib or sunitinib and BGJ 398. Moreover, FGFR1/2 and VEGFR1/2 were co-localized in IM-resistant GIST T-1R cells, and the direct interaction between the aforementioned RTKs was confirmed by co-immunoprecipitation. In contrast, IM-resistant GIST 430 cells expressed lower basal levels of FGF2 and VEGF-A. Despite the increased expression VEGFR1 and FGFR1/2 in GIST 430 cells, these RTKs were not co-localized and co-immunoprecipitated. Moreover, no synergy between FGFR and VEGFR inhibitors was observed for the IM-resistant GIST 430 cell line. Collectively, the dual targeting of FGFR and VEGFR pathways in IM-resistant GISTs is not limited to the synergistic anti-angiogenic treatment effects. The dual inhibition of FGFR and VEGFR pathways in IM-resistant GISTs potentiates the proapoptotic and anti-proliferative activities of the corresponding RTKi. Mechanistically, the FGF2-induced activation of the FGFR pathway turns on VEGFR signaling via the overproduction of VEGF-A, induces the interaction between FGFR1/2 and VEGFR1, and thereby renders cancer cells highly sensitive to the dual inhibition of the aforementioned RTKs. Thus, our data uncovers the novel mechanism of the cross-talk between the aforementioned RTKs in IM-resistant GISTs lacking secondary KIT mutations and suggests that the dual blockade of FGFR and VEGFR signaling might be an effective treatment strategy for patients with GIST-acquired IM resistance via KIT-independent mechanisms.

Predictive performance of [18F]F-fibroblast activation protein inhibitor (FAPI)-42 positron emission tomography/computed tomography (PET/CT) in evaluating response of recurrent or metastatic gastrointestinal stromal tumors: complementary or alternative to [18F]fluorodeoxyglucose (FDG) PET/CT?

Background: Accurately and promptly predicting the response of gastrointestinal stromal tumors (GISTs) to targeted therapy is essential for optimizing treatment strategies. However, some fractions of recurrent or metastatic GISTs present as non-FDG-avid lesions, limiting the value of [18F]fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG PET/CT) in treatment evaluation. This study evaluated the efficacy of [18F]F-fibroblast activation protein inhibitor (FAPI)-42 [18F]FAPI-42) PET/CT for assessing the treatment response in recurrent or metastatic GISTs, in comparison to [18F]FDG PET/CT and explores a model integrating PET/CT imaging and clinical parameters to optimize the clinical use of these diagnostic tools. Methods: Our retrospective analysis included 27 patients with recurrent or metastatic GISTs who underwent [18F]FAPI-42 PET/CT and [18F]FDG PET/CT at baseline before switching targeted therapy. Treatment response status was divided into a progression group (PG) and a non-progression group (NPG) based on the Response Criteria in Solid Tumors (RECIST) 1.1, according to the contrast-enhanced computed tomography (CT) scan at six months. [18F]FAPI-42 and [18F]FDG PET/CT parameters including the mean standardized uptake value (SUVmean), the standard uptake value corrected for lean body mass (SULpeak), the maximum standardized uptake value (SUVmax), tumor-to-blood pool SUV ratio (TBR), tumor-to-liver SUV ratio (TLR), metabolic tumor volume (MTV)/FAPI-positive tumor volume (GTV-FAPI), total lesion glycolysis (TLG)/FAPI-positive total lesion accumulation (TLF) were correlated with the response status to identify indicative of treatment response. The predictive performance of them was quantified by generating receiver operating characteristic curves (ROC), calibration curves, and cross-validation. Results: A total of 110 lesions were identified in 27 patients. Compared with PG, NPG was associated with lower levels of TBR and SUVmean in FDG PET/CT (TBR-FDG, SUVmean-FDG; P=0.033 and P=0.038, respectively), with higher SULpeak and TLF in FAPI PET/CT (SULpeak-FAPI, TLF-FAPI; P=0.10 and P=0.049, respectively). The predictive power of a composite-parameter model, including TBR-FDG, SULpeak-FAPI, gene mutation, and type of targeted therapy [area under the curve (AUC) =0.865], was superior to the few-parameter models incorporating TBR-FDG (AUC =0.637, P<0.001), SULpeak-FAPI (AUC =0.665, P<0.001) or both (AUC =0.721, P<0.001). Conclusions: Both [18F]FAPI-42 PET/CT and [18F]FDG PET/CT have value in predicting the treatment response of recurrent or metastatic GISTs. And [18F]FAPI-42 PET/CT offers synergistic value when used in combination with [18F]FDG PET/CT. Notably, the nomogram generated from the model incorporating [18F]FAPI-42 PET/CT, [18F]FDG PET/CT parameters, gene mutation, and type of targeted therapy could yield more precise predictions of the response of recurrent metastatic GISTs.

A rare case of extragastrointestinal stromal tumor of vocal cord - case report.

Gastrointestinal stromal tumors (GISTs) are the mesenchymal tumors of the gastrointestinal tract. Extra Gastrointestinal stromal tumors (EGISTs) are rare neoplasms that occur outside the gastrointestinal tract [1]. Miettinen et al. [2] described the first EGIST in 1999. EGIST accounts for 10% of all GISTs [3]. The main distinction between GIST and EGIST is the site of origin of the primary tumor, as GIST occurs throughout the GI tract, from the esophagus to the anus, whereas EGIST is a tumor without any connection with the intestinal wall and are reported in the retroperitoneum, mesentery, and omentum [4]. Hu et al. [5] reported a first case report of EGIST of larynx.We present a second case report of Extra-gastrointestinal stromal tumor of larynx a 47-year-old male reported to ENT Department Command Hospital Central Command Lucknow with complaints of Hoarseness. On examination found to have right vocal cord growth for which he underwent excision of right vocal cord growth. Histopathological examination showed typical of a spindle-cell GIST, showing strong immunoreactivity for CD 117, DOG1, Vimentin and CD 99. 6 months follow up post surgery with no recurrence.

Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are typical gastrointestinal tract neoplasms. Imatinib is the first-line therapy for GIST patients. Drug resistance limits the long-term effectiveness of imatinib. The regulatory effect of insulin-like growth factor 2 (IGF2) has been confirmed in various cancers and is related to resistance to chemotherapy and a worse prognosis. AIM: To further investigate the mechanism of IGF2 specific to GISTs. METHODS: IGF2 was screened and analyzed using Gene Expression Omnibus (GEO: GSE225819) data. After IGF2 knockdown or overexpression by transfection, the phenotypes (proliferation, migration, invasion, apoptosis) of GIST cells were characterized by cell counting kit 8, Transwell, and flow cytometry assays. We used western blotting to evaluate pathway-associated and epithelial-mesenchymal transition (EMT)-associated proteins. We injected transfected cells into nude mice to establish a tumor xenograft model and observed the occurrence and metastasis of GIST. RESULTS: Data from the GEO indicated that IGF2 expression is high in GISTs, associated with liver metastasis, and closely related to drug resistance. GIST cells with high expression of IGF2 had increased proliferation and migration, invasiveness and EMT. Knockdown of IGF2 significantly inhibited those activities. In addition, OE-IGF2 promoted GIST metastasis in vivo in nude mice. IGF2 activated IGF1R signaling in GIST cells, and IGF2/IGF1R-mediated glycolysis was required for GIST with liver metastasis. GIST cells with IGF2 knockdown were sensitive to imatinib treatment when IGF2 overexpression significantly raised imatinib resistance. Moreover, 2-deoxy-D-glucose (a glycolysis inhibitor) treatment reversed IGF2 overexpression-mediated imatinib resistance in GISTs. CONCLUSION: IGF2 targeting of IGF1R signaling inhibited metastasis and decreased imatinib resistance by driving glycolysis in GISTs.

Deep learning analysis for differential diagnosis and risk classification of gastrointestinal tumors.

OBJECTIVES: Recently, artificial intelligence (AI) has been applied to clinical diagnosis. Although AI has already been developed for gastrointestinal (GI) tract endoscopy, few studies have applied AI to endoscopic ultrasound (EUS) images. In this study, we used a computer-assisted diagnosis (CAD) system with deep learning analysis of EUS images (EUS-CAD) and assessed its ability to differentiate GI stromal tumors (GISTs) from other mesenchymal tumors and their risk classification performance. MATERIALS AND METHODS: A total of 101 pathologically confirmed cases of subepithelial lesions (SELs) arising from the muscularis propria layer, including 69 GISTs, 17 leiomyomas and 15 schwannomas, were examined. A total of 3283 EUS images were used for training and five-fold-cross-validation, and 827 images were independently tested for diagnosing GISTs. For the risk classification of 69 GISTs, including very-low-, low-, intermediate- and high-risk GISTs, 2,784 EUS images were used for training and three-fold-cross-validation. RESULTS: For the differential diagnostic performance of GIST among all SELs, the accuracy, sensitivity, specificity and area under the receiver operating characteristic (ROC) curve were 80.4%, 82.9%, 75.3% and 0.865, respectively, whereas those for intermediate- and high-risk GISTs were 71.8%, 70.2%, 72.0% and 0.771, respectively. CONCLUSIONS: The EUS-CAD system showed a good diagnostic yield in differentiating GISTs from other mesenchymal tumors and successfully demonstrated the GIST risk classification feasibility. This system can determine whether treatment is necessary based on EUS imaging alone without the need for additional invasive examinations.

Gastrointestinal stromal tumor with small cell carcinoma infiltration: a case report.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the digestive system. They usually occur in the gastrointestinal tract. However, we discovered a rare phenomenon in which small cell carcinoma infiltrated the GIST of a patient. The patient came to the hospital and presented with chest tightness and shortness of breath for 2 months and a dry cough for half a month. As the ancillary tests were refined, it was discovered that he also had a lesion in the pelvic cavity. After pathological examination of the core needle biopsy (CNB) samples from the pelvic cavity lesion, the patient was diagnosed with GIST with small cell carcinoma infiltration. The patient is currently receiving a chemotherapy regimen of etoposide combined with cisplatin.

Gastrointestinal Stromal Tumors: A Retrospective Study at a Tertiary Care Center in Saudi Arabia in the Last Decade.

INTRODUCTION: Gastrointestinal stromal tumors (GISTs) are a significant subset of mesenchymal tumors primarily found in the gastrointestinal tract, impacting diagnostic and therapeutic approaches. Understanding their epidemiology is crucial for improving patient care and advancing treatment strategies. METHODOLOGY: Our study at a Saudi tertiary hospital analyzed 50 patients with GIST, focusing on demographics, tumor locations, and risk assessments. We examined predictors of tumor size, including mitosis frequency, and assessed the impact of anatomical location and risk on clinical outcomes using RStudio software (Posit, Boston, MA). RESULTS: Among 50 patients with GIST, 36 (72.0%) were male with a median age of 60.5 years, and most tumors (33, 66.0%) were in the stomach. Risk assessments categorized tumors as follows: 20 (40.0%) low risk, 12 (24.0%) high risk, 7 (14.0%) moderate risk, 7 (14.0%) very low risk, and 4 (8.0%) no risk. Most tumors were low-grade (41, 82.0%) and nonmetastatic (47, 94.0%), predominantly spindle cell type (37, 74.0%). Tumor size varied significantly across risk categories: high-risk tumors averaged 10.3 cm versus 0.5 cm for no risk and 3.5 cm for very low risk (P < 0.001). Mitosis frequency differed significantly by risk category and tumor grade (P < 0.001). Tumor grade varied notably with risk categories and morphologic types, especially high-grade tumors in high-risk groups (8, 66.7%) and epithelioid tumors (2, 100%). Multivariable analysis identified predictors of tumor size: anatomical location (extra-GI, intra-abdominal; beta = 7.08, P = 0.011) and risk assessment (low risk, beta = 6.91, P = 0.001; moderate risk, beta = 11.2, P < 0.001; high risk, beta = 8.93, P < 0.001). Liver metastasis did not differ significantly across gender, anatomical location, risk assessment, or tumor grade. CONCLUSIONS: In Saudi Arabia, GISTs predominantly affect males and are primarily located in the stomach. Our findings highlight significant variations in tumor size and grade based on risk assessments and anatomical location. Most GISTs were low-grade, nonmetastatic, and spindle cell type, emphasizing the need for enhanced research to improve diagnostics, tailor treatments, and optimize outcomes in the region.

Hypervascular gastrointestinal stromal tumor: a rare case report.

Introduction and importance: To document a case of an ileal gastrointestinal stromal tumor that caused a massive lower gastrointestinal hemorrhage. Case presentation: A 55-year-old man presented with multiple episodes of melena and decreased hemoglobin levels. Computed tomography angiography (CTA) revealed a hypervascularized ileal mass. Clinical discussion: The mass was surgically excised, and the patient's hemoglobin levels stabilized. Histopathological findings confirmed it to be a low-grade gastrointestinal stromal tumor (G1 GIST). Conclusion: GISTs are infrequent clinical entities that should be kept in mind when managing patients with gastrointestinal hemorrhage of unknown origin. Using proper imaging modalities is essential for the accurate diagnosis of such tumors, with CTA proving to be particularly effective in identifying hypervascularized tumors.

Survival outcomes and prognostic factors of advanced gastrointestinal stromal tumors: in the era of multiple tyrosine kinase inhibitors.

Background: Tyrosine kinase inhibitors (TKIs) have shown great efficacy in the treatment of advanced gastrointestinal stromal tumors (GISTs), significantly prolonging the survival of patients. In the era of imatinib, a few studies reported some prognostic factors for patients with advanced GISTs, such as age, sex, performance status, diameter of the largest lesions, KIT exon mutations, and some hematological examination results. However, with the advent of more TKIs, the prognostic factors for patients with advanced GISTs have not been fully understood in the era of multiple TKIs. In this study, we aimed to identify independent prognostic factors associated with the survival of patients diagnosed with advanced GISTs. Methods: Data on clinicopathologic characteristics, treatment approaches, and survival were retrospectively collected for patients with primary unresectable or recurrent GISTs treated from January 2010 to July 2023 at the First Affiliated Hospital of Chongqing Medical University, China. Univariable and multivariable Cox proportional hazards regression models were used to identify independent prognostic factors of survival. Results: A total of 194 patients were included in the analysis. The median follow-up duration was 59.9 months (range, 2.7-141.7 months). The median overall survival (mOS) in this cohort was 76.5 months (95% confidence interval, 63.4 to 89.6 months). All patients received TKI therapy during the follow-up period, and 56.2% received two or more types of TKIs. In multivariable Cox analysis, younger age, a single lesion at enrollment, no previous use of TKIs, smaller tumor burden, good Eastern Cooperative Oncology Group performance status (ECOG PS ≤1), and lesions limited to the liver were independent prognostic factors for better survival. Conclusions: We found that a single lesion at enrollment, no previous use of TKIs, a smaller tumor burden, and lesions limited to the liver were associated with better survival. Drug resistance is a severe challenge for advanced GISTs, and several factors mentioned above may be correlated with the development of drug resistance, leading to the poor survival of patients.

Gastrointestinal Stromal Tumors of the Stomach: Is There Any Advantage of Robotic Resections? A Systematic Review and Meta-Analysis.

Background: The role of robotic surgery for gastrointestinal stromal tumor (GIST) resection remains unclear. This systematic review and meta-analysis aimed to investigate the outcomes of robotic versus laparoscopic surgery in patients requiring surgery for gastric GISTs. Methods: MEDLINE, EMBASE, and the Cochrane databases were searched from inception to September 4, 2023. Two independent reviewers conducted a systematic review of the literature to select all types of analytic studies comparing robotic versus laparoscopic surgery for GISTs and reporting intraoperative, postoperative, and/or pathological outcomes. Results: Overall, 4 retrospective studies were selected, including a total of 264 patients, specifically 111 (42%) in the robotic and 153 (58%) in the laparoscopic group. Robotic surgery was associated with longer operating time (+42.46 min; 95% confidence interval [CI]: 9.34, 75.58; P=0.01; I2: 85%) and reduced use of mechanical staplers (odds ratio [OR]: 0.05; 95%CI: 0.02, 0.11; P<0.00001; I2: 92%;) compared with laparoscopy. Although nonsignificant, conversion to open surgery was less frequently reported for robotic surgery (2.7%) than laparoscopy (5.2%) (OR: 0.59; 95%CI: 0.17, 2.03; P=0.4; I2: 0%). No difference was found for postoperative and oncological outcomes. Conclusions: Robotic surgery for gastric GISTs provides similar intraoperative, postoperative, and pathological outcomes to laparoscopy, despite longer operative time.

Clinical course of asymptomatic duodenal subepithelial lesions.

BACKGROUND/AIMS: There is limited knowledge regarding the management of duodenal subepithelial lesions (SELs) owing to a lack of understanding of their natural course. This study aimed to assess the natural course of asymptomatic duodenal SELs and provide management recommendations. METHODS: Patients diagnosed with duodenal SELs and followed up for a minimum of 6 months were retrospectively investigated. RESULTS: Among the 443,533 patients who underwent esophagogastroduodenoscopy between 2008 and 2020, duodenal SELs were identified in 0.39% (1,713 patients). Among them, 396 duodenal SELs were monitored for a median period of 72.5 months (interquartile range, 37.7-111.3 mo). Of them, 16 SELs (4.0%) showed substantial changes in size or morphology at a median follow-up of 35.1 months (interquartile range, 21.7-51.4 mo). Of these SELs with substantial changes, tissues of two SELs were acquired using endoscopic ultrasound-guided fine needle aspiration biopsy: one was a lipoma and the other was non-diagnostic. Three SELs were surgically or endoscopically removed; two were diagnosed as gastrointestinal stromal tumors, and one was a lipoma. An initial size of 20 mm or larger was associated with substantial changes during follow-up (p = 0.016). CONCLUSION: While the majority of duodenal SELs may not exhibit substantial interval changes, regular follow-up with endoscopy may be necessary for cases with an initial size of 20 mm or larger, considering a possibility of malignancy.

Glycolysis in gastrointestinal stromal tumor: a brief overview.

Gastrointestinal stromal tumor (GIST) is the most prevalent mesenchymal tumor of the digestive tract. Its growth is primarily influenced by mutations in KIT or PDGFRA. Surgery is the primary treatment option for GIST; however, KIT inhibitors, such as imatinib, are used for inoperable cases. Resistance to imatinib is an upcoming challenge, especially because the effectiveness of alternative drugs is limited. Enhancement of the glycolysis pathway in cancer cells has been identified as a key feature in cancer. This unique metabolic activity has implications on tumor growth, prognosis, and resistance to therapy, even in GIST. Members of the glucose transporter (GLUT) family (particularly GLUT-1) play a significant role in GIST progression and response to treatment. Diagnostic imaging using 18F-fluorodeoxyglucose positron emission tomography/computed tomography, which enables visualization of glucose metabolism, can aid in GIST diagnosis and risk assessment. The interplay between glycolysis and GIST can lead to the development of various therapeutic strategies, especially those involving glycolysis-related molecules, such as hexokinase and lactate dehydrogenase. However, further research is required to understand the full spectrum of glycolysis in GIST and its therapeutic potential. Herein, we present an exhaustive overview and analysis of the role of glycolysis in GIST, especially as a therapeutic target.

Robot-assisted laparoscopic combined with endoscopic partial gastrectomy (RALE-PG) for the treatment of gastric gastrointestinal stromal tumors in challenging anatomical locations: single-center experience.

Background: Gastric gastrointestinal stromal tumors in challenging anatomical locations are difficult to remove. Methods: This study retrospectively analyzed the clinical data of 12 patients with gastric GISTs in challenging anatomical locations who underwent robot-assisted laparoscopic combined with endoscopic partial gastrectomy (RALE-PG) and manual suturing of the gastric wall. Results: This study included 12 patients with a mean age of 56.8 ± 9.8 years and a mean BMI of 23.9 ± 1.9 kg/m2. Tumors were located in the GEJ (n = 3), lesser curvature (n = 3), posterior gastric wall (n = 3) and antrum (n = 3). The cardia and pylorus were successfully preserved in all patients regardless of the tumor location. The mean tumor size was 4.5 ± 1.4 cm. The mitotic-count/50 mm2 was less than 5 in all patients (100%). There was no intraoperative tumor rupture (0%) and no conversion to open surgery (0%). The median operation time was 122 (97-240) min, and the median blood loss volume was 10 (5-30) ml. The median postoperative VAS score was 2 (2-4). The median time to first flatus was 2 (2-3) days. The median time to first fluid intake was 2 (2-3) days. The median time to first ambulation after the operation was 3 (2-4) days. No cases of anastomotic stenosis or leakage were found. The median time to drain removal for 6 patients was 5 (4-7) days. The median time to nasogastric tube removal for all patients was 2 (1-5) days. The median postoperative hospital stay was 5 (4-8) days. One patient (female/41 year) developed moderate anemia (Clavien-Dindo grade II complication). There was no unplanned readmission within 30 days after the operation. The median distance from the tumor to the resection margin was 1 (1-2) cm. R0 resection was achieved in all patients. The median follow-up period was 19 (10-25) months, and all patients survived with no recurrence or metastasis. Conclusions: RALE-PG is a safe, feasible and advantageous technique for treating GISTs in challenging anatomical locations. It can be used to accurately remove the tumor while preserving gastric function to the greatest extent, but long-term oncologic outcomes need to be evaluated in a study with a larger sample size and longer follow-up period.

An ultrasound based method for predicting the malignant potential of primary gastrointestinal stromal tumors preoperatively.

OBJECTIVE: Gastrointestinal stromal tumors (GISTs) are difficult to identify the risk level accurately without surgical pathological confirmation. The purpose of our study was to propose a noninvasive prediction method for predicting the malignant potential of GISTs preoperatively by using contrast-enhanced ultrasound (CEUS) with gastric distention. METHODS: We reviewed 47 GISTs who underwent CEUS from April 2017 to August 2023 retrospectively, all the lesions were certificated by pathology after surgery. The age of the patient, size of the lesion, shape, necrosis, calcification in the lesion, perfusion parameters including arrival time (AT), peak intensity (PI), time to peak (TTP), and area under the curve (AUC) of the lesion and surrounding normal tissue were analyzed. Logistic regression analyses were performed. Of the 47 GISTs, 26 were high-risk and 21 low-risk tumors respectively. RESULTS: Compared with low-risk GISTs, high-risk GIST had faster AT (7.7s vs. 11.5s, p < 0.05), higher PI (15.2dB vs. 12.5dB, p < 0.05), and larger size (4.4 cm vs. 2.2 cm, p < 0.001). In multivariate logistic regression, AT, PI, and size were significant features. The corresponding regression equation In (p/(1-p)=-5.9 + 4.5 size + 4.6 PI + 4.0 AT). CONCLUSION: The size, AT, and PI of the GISTs on CEUS can be used as parameters for a noninvasive risk level prediction model of GISTs. This model may help identify the different risk levels of GISTs before surgery.

Efficacy of real-time artificial intelligence-aid endoscopic ultrasonography diagnostic system in discriminating gastrointestinal stromal tumors and leiomyomas: a multicenter diagnostic study.

Background: Gastrointestinal stromal tumors (GISTs) represent the most prevalent type of subepithelial lesions (SELs) with malignant potential. Current imaging tools struggle to differentiate GISTs from leiomyomas. This study aimed to create and assess a real-time artificial intelligence (AI) system using endoscopic ultrasonography (EUS) images to differentiate between GISTs and leiomyomas. Methods: The AI system underwent development and evaluation using EUS images from 5 endoscopic centers in China between January 2020 and August 2023. EUS images of 1101 participants with SELs were retrospectively collected for AI system development. A cohort of 241 participants with SELs was recruited for external AI system evaluation. Another cohort of 59 participants with SELs was prospectively enrolled to assess the real-time clinical application of the AI system. The AI system's performance was compared to that of endoscopists. This study is registered with Chictr.org.cn, Number ChiCT2000035787. Findings: The AI system displayed an area under the curve (AUC) of 0.948 (95% CI: 0.921-0.969) for discriminating GISTs and leiomyomas. The AI system's accuracy (ACC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) reached 91.7% (95% CI 87.5%-94.6%), 90.3% (95% CI 83.4%-94.5%), 93.0% (95% CI 87.2%-96.3%), 91.9% (95% CI 85.3%-95.7%), and 91.5% (95% CI 85.5%-95.2%), respectively. Moreover, the AI system exhibited excellent performance in diagnosing ≤20 mm SELs (ACC 93.5%, 95% CI 0.900-0.969). In a prospective real-time clinical application trial, the AI system achieved an AUC of 0.865 (95% CI 0.764-0.966) and 0.864 (95% CI 0.762-0.966) for GISTs and leiomyomas diagnosis, respectively, markedly surpassing endoscopists [AUC 0.698 (95% CI 0.562-0.834) for GISTs and AUC 0.695 (95% CI 0.546-0.825) for leiomyomas]. Interpretation: We successfully developed a real-time AI-assisted EUS diagnostic system. The incorporation of the real-time AI system during EUS examinations can assist endoscopists in rapidly and accurately differentiating various types of SELs in clinical practice, facilitating improved diagnostic and therapeutic decision-making. Funding: Science and Technology Commission Foundation of Shanghai Municipality, Science and Technology Commission Foundation of the Xuhui District, the Interdisciplinary Program of Shanghai Jiao Tong University and the Research Funds of Shanghai Sixth people's Hospital.

Preoperative CT-based radiomics and deep learning model for predicting risk stratification of gastric gastrointestinal stromal tumors.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are clinically heterogeneous with various malignant potential in different individuals. It is crucial to explore a reliable method for preoperative risk stratification of gastric GISTs noninvasively. PURPOSE: To establish and evaluate a machine learning model using the combination of computed tomography (CT) morphology, radiomics, and deep learning features to predict the risk stratification of primary gastric GISTs preoperatively. METHODS: The 193 gastric GISTs lesions were randomly divided into training set, validation set, and test set in a ratio of 6:2:2. The qualitative and quantitative CT morphological features were assessed by two radiologists. The tumors were segmented manually, and then radiomic features were extracted using PyRadiomics and the deep learning features were extracted using pre-trained Resnet50 from arterial phase and venous phase CT images, respectively. Pearson correlation analysis and recursive feature elimination were used for feature selection. Support vector machines were employed to build a classifier for predicting the risk stratification of GISTs. This study compared the performance of models using different pre-trained convolutional neural networks (CNNs) to extract deep features for classification, as well as the performance of modeling features from single-phase and dual-phase images. The arterial phase, venous phase and dual-phase machine learning models were built, respectively, and the morphological features were added to the dual-phase machine learning model to construct a combined model. Receiver operating characteristic (ROC) curves were used to evaluate the efficacy of each model. The clinical application value of the combined model was determined through the decision curve analysis (DCA) and the net reclassification index (NRI) was analyzed. RESULTS: The area under the curve (AUC) of the dual-phase machine learning model was 0.876, which was higher than that of the arterial phase model or venous phase model (0.813, 0.838, respectively). The combined model had best predictive performance than the above models with an AUC of 0.941 (95% CI: 0.887-0.974) (p = 0.012, Delong test). DCA demonstrated that the combined model had good clinical application value with an NRI of 0.575 (95% CI: 0.357-0.891). CONCLUSION: In this study, we established a combined model that incorporated dual-phase morphology, radiomics, and deep learning characteristics, which can be used to predict the preoperative risk stratification of gastric GISTs.