Neoadjuvant therapy targeting genotype-specific gastrointestinal stromal tumors (GISTs) may be indicated in select cases. While the majority of patients respond to Imatinib with a reduction in tumor size, some exhibit either poor response or resistance, necessitating the exploration of alternative therapeutic strategies. This report describes a high-risk patient facing potential multiorgan resections whose tumor responded poorly after 14 months of Imatinib therapy. After 8 months of transitioning to Ripretinib treatment, there was a 26% reduction in the largest tumor diameter. This improvement allowed better delineation of the tumor from the surrounding tissues, which in turn made it possible to perform an R0 resection while preserving the possibly involved organs. To our knowledge, this is the first case report of Ripretinib as a neoadjuvant therapy for GIST with peripheral organ invasion to achieve complete resection. This case report may present the effectiveness of Ripretinib and introduce a relatively novel approach to clinical treatment.

To identify and classify submucosal tumors by building and validating a radiomics model with gastrointestinal endoscopic ultrasonography (EUS) images.

A total of 144 patients diagnosed with submucosal tumors through gastrointestinal EUS were collected between January 2019 and October 2020. There are 1952 radiomic features extracted from each patient's EUS images. The statistical test and the customized least absolute shrinkage and selection operator regression were used for feature selection. Subsequently, an extremely randomized trees algorithm was utilized to construct a robust radiomics classification model specifically tailored for gastrointestinal EUS images. The performance of the model was measured by evaluating the area under the receiver operating characteristic curve.

The radiomics model comprised 30 selected features that showed good discrimination performance in the validation cohorts. During validation, the area under the receiver operating characteristic curve was calculated as 0.9203 and the mean value after 10-fold cross-validation was 0.9260, indicating excellent stability and calibration. These results confirm the clinical utility of the model.

Utilizing the dataset provided curated from gastrointestinal EUS examinations at our collaborating hospital, we have developed a well-performing radiomics model. It can be used for personalized and non-invasive prediction of the type of submucosal tumors, providing physicians with aid for early treatment and management of tumor progression.

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the digestive tract, often accompanied by a high risk of recurrence and drug resistance. Huaier (Trametes robiniophila Murr), a traditional Chinese medicinal fungus, has demonstrated potent anticancer properties and is widely used as an adjuvant treatment for liver, breast, gastric, colon, and non-small cell lung cancers. However, its effects and molecular mechanisms in GIST remain unclear.

This study aims to explore the inhibitory effects and underlying mechanisms of Huaier on GIST through network pharmacology and experimental validation.

Initially, we utilized a publicly accessible database to identify the core targets and principal pathways associated with Huaier's therapeutic effects on gastrointestinal stromal tumors. To further evaluate its biological impact, cell viability, proliferation, migration, and invasion were assessed through CCK-8 and EdU assays, wound healing tests, and Transwell experiments. Apoptotic cell death was quantified using flow cytometry analysis. Additionally, the influence of Huaier extract on the expression levels of JAK2 and STAT3 proteins was examined via Western blotting. Finally, a subcutaneous xenograft mouse model was employed to investigate the anti-tumor efficacy of Huaier in vivo.

In this study, GAPDH, TNF, STAT3, ESR1, EGFR, IL6, CCND1, PTGS2, BCL2L1, and MAPK3 were identified as shared molecular targets, with the JAK/STAT signaling pathway recognized as the pivotal regulatory mechanism. Experimental findings demonstrated that Huaier exerted inhibitory effects on the proliferation, migration, and invasion of GIST-T1 and GIST-882 cells, exhibiting both dose- and time-dependent responses. Furthermore, Huaier was found to promote apoptosis in these cells. Western blot analysis revealed that treatment with Huaier extract significantly decreased the phosphorylation levels of JAK2 and STAT3, thereby suppressing the activation of the JAK2/STAT3 signaling cascade. In vivo experiments further substantiated these findings, showing that Huaier treatment markedly reduced tumor size and inhibited tumor progression.

Our results suggest that Huaier may inhibit the growth of GIST cells by inhibiting the JAK2/STAT3 signaling pathway, reduce cell proliferation, induce apoptosis, reduce cell migration and invasion, and show anti-tumor effects in vivo and in vitro.

Imatinib is the first-line targeted therapy for gastrointestinal stromal tumor (GIST), but resistance frequently occurs during treatment, limiting its efficacy and clinical application. We performed high-throughput sequencing of tissue specimens from imatinib-resistant GIST patients, and identified significantly high expression of polymeric immunoglobulin receptor (PIGR) in imatinib-resistant cell lines. Further investigation revealed that PIGR binds specifically to LINC00870. The findings from in vitro cell functional experiments provide evidence of a strong association between LINC00870 and PIGR and the processes of proliferation and metastasis in GIST. Overexpression of LINC00870 in GIST significantly inhibits the glycosylation modification and secretion of the extracellular region of PIGR, leading to immune dysregulation. The inhibition of PIGR or LINC00870 effectively surmounts imatinib resistance. Our study identified PIGR as a critical molecule in regulating GIST imatinib resistance and elucidated the mechanism by which PIGR promotes imatinib resistance through LINC00870 inhibition of PIGR glycosylation modifications. These findings provide a new theoretical basis for blocking drug resistance and improving prognosis in GIST.

To assess and compare the diagnostic efficiency of histogram analysis of monochromatic and iodine images derived from spectral CT in predicting Ki-67 expression in gastric gastrointestinal stromal tumors (gGIST).

Sixty-five patients with gGIST who underwent spectral CT were divided into a low-level Ki-67 expression group (LEG, Ki-67 < 10%, n = 33) and a high-level Ki-67 expression group (HEG, Ki-67 ≥ 10%, n = 32). Conventional CT features were extracted and compared. Histogram parameters were extracted from monochromatic and iodine images, respectively. The diagnostic efficiency of the histogram parameters from monochromatic and iodine images was assessed and compared between the two groups. Spearman's correlation analysis was used to correlate histogram parameters with Ki-67 expression.

The HEG was more likely to present with an irregular shape and a larger size than the LEG (all p < 0.05). Regarding histogram parameters, the HEG showed higher maximum, mean, Perc.10, Perc.25, Perc.50, Perc.75, Perc.90, Perc.99, SD, variance, and CV of monochromatic images; higher maximum, Perc.99, and entropy of iodine images, compared with the LEG (all p < 0.003125). ROC analysis showed that significant histogram parameters of monochromatic and iodine images allowed for effective differentiation between LEG and HEG. DeLong's test showed that the diagnostic efficiency of histogram parameters in monochromatic images (Perc.90) was superior to that of iodine images (maximum) (p = 0.010). A positive correlation was observed between the significant histogram parameters and Ki-67 expression (all p < 0.05).

Both histogram analysis of monochromatic and iodine images derived from spectral CT can predict Ki-67 expression in gGIST, and the diagnostic efficacy of monochromatic images is superior to iodine images.

To develop and validate a machine learning (ML) model which combined computed tomography (CT) semantic and radiomics features to preoperatively predict Ki-67 expression in gastrointestinal stromal tumors (GISTs) patients. We retrospectively collected the clinical, imaging and pathological data of 149 GISTs patients. We randomly assigned the patients in a ratio of 7:3 to a training set (104 cases) and a validation (45 cases) set. We divided the patients into low and high Ki-67 expression group according to postoperative pathology. CT semantic features were analyzed from preoperative enhancement CT images and radiomics features were extracted from venous phase-enhanced images. We used intraclass correlation coefficient, maximal relevance and minimal redundancy and least absolute shrinkage and selection operator method to screen radiomics features and build radiomics label. 6 ML models were used for model construction. Receiver operating characteristic curves were used to evaluate the predictive efficiency of ML models. SHAP analysis was used to explain the contribution of different variables and their risk threshold. AUC of radscores in predicting Ki-67 expression of GIST patients were 0.749 and 0.729 in training and validation set. Among the 6 ML models, SVM exhibited best prediction accuracy. AUC of SVM model in predicting Ki-67 expression of GIST patients were 0.840, 0.767 and 0.832 in training, validation and test set. SHAP analysis showed that radscores and tumor diameter had highly positive contribution to the model. Therefore, the interpretable SVM model can predict Ki-67 expression of GISTs patients individually before surgery, which can provide reliable imaging biomarkers for clinical treatment decisions.

Gastrointestinal tumors (GIST) are mesenchymal soft tissue tumors that are commonly found in the stomach and are classified according to their site, size, and degree of mitosis.

A 40-year-old female patient presented to the emergency department complaining of abdominal pain; she was admitted, underwent multiple investigations, and was diagnosed with GIST; she was discharged and readmitted due to food intolerance; the patient was started on imatinib treatment but had a hemorrhagic shock while on therapy due to massive intraperitoneal hemorrhage that needed a lifesaving operation.

Intraperitoneal bleeding is rare but should be taken into consideration in treating a patient with GIST, especially when the tumor has a risk for complications as enormous and even when proper treatment with chemotherapy agents such as imatinib is started. So, chemotherapy started for two weeks, but later, the patient developed symptoms and signs of intraabdominal bleeding and was diagnosed radiologically. However, due to patient instability, the decision was made to resection, which was done successfully. She was extubated and showed no signs of bleeding postoperatively.

This case report sheds light on the rare presentation of a giant gastric GIST and the challenges associated with its management. The patient had a poor response to medical treatment with imatinib, which aimed to reduce the tumor size. Moreover, surgical management can be the best first line of management in giant GIST, as the larger the size of the GIST, the more complications can occur.

Imatinib (IMA) has received approval as the primary treatment for gastrointestinal stromal tumors (GIST). Nonetheless, approximately half of the patients with advanced GIST show disease advancement following IMA treatment. Presently, the efficacy of secondary and tertiary medications in addressing various GIST secondary mutations is somewhat restricted. Consequently, there is a significant medical demand for the creation of kinase inhibitors that extensively block secondary drug-resistant mutations in advanced GIST. Ripretinib (RPT) is a new, switch-control tyrosine kinase inhibitors that can suppress different mutations of KIT and PDGFRA via a dual mechanism of action.

To investigate the literature on RPT to assess an effective, safe, and successful treatment strategy against advanced GIST.

The present systematic review and meta-analysis was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, Embase, Cochrane, Web of Science and ClinicalTrials.gov databases were screened from January 1, 2003 to May 1, 2024.

A total of 4 studies were included, with a total of 507 patients enrolled. The objective response rate (ORR) of the RPT-treated advanced GIST was 17% (95%CI: 0.11-0.27), while the disease control rate (DCR) was 66% (95%CI: 0.59-0.73). The overall occurrence of adverse events with varying degrees was 97% (95%CI: 0.93-1), whereas that of grade ≥ 3 adverse reactions was 42% (95%CI: 0.28-0.63). The sensitivity analysis revealed that omitting some studies did not yield statistically notable variances in the aggregate data regarding the ORR, DCR, and the occurrence of adverse events of grade 3 or higher. The publication bias was absent because no significant asymmetry was observed in Begg's funnel plot in all studies.

RPT has favorable efficacy profiles in GIST patients, but the adverse reactions are obvious, and patient management needs to be strengthened to achieve better safety and tolerability.

Understanding the current status and future trends of cancer burdens by systems provides important information for specialists, policymakers, and specific risk populations.

The aim of this study was to compare the current and future cancer burdens of the gastrointestinal (GI) and respiratory tracts in terms of their magnitude and distribution. Data from a total of eight cancers of the digestive and respiratory tracts in the Global Burden of Disease (GBD) database were collected. The age-standardized incidence/death rates (ASIR/ASDRs), disability-adjusted life years (DALYs), and estimated annual percentage changes (EAPCs) were analyzed. Future trends were predicted with Bayesian age-period-cohort (BAPC) and NORDPRED models.

In 2019, there was a significant increase in DALY for both digestive and respiratory tract cancers compared to 1990. Meanwhile, ASIR increased slightly and ASDR decreased notably. In 2019, the global cancer burdens of respiratory and digestive tracts were 38568363.53 and 66912328.72 in DALY, 34.28 and 55.32 in ASIR, and 656.82 and 808.22 in ASDR per 100,000 population with changes of +54.63% and +43.93%, +2.92% and +5.65%, and -17.39% and -26.83% compared to those in 1990, respectively. Significant cross-regional differences in the cancer burdens were observed among the regions. Compared to four representative chronic diseases, the burden of cancers showed less remission and greater global inequalities. The burdens of both digestive and respiratory tract cancers were higher in males than in females in terms of the ASIR, ASDR, and DALY. The incidence and mortality rates of respiratory tract cancers were up to 3-4 times higher in males than in females, whereas the difference between male and female rates of digestive tract cancers was relatively smaller. The main risk factor associated with all kinds of digestive and respiratory tract cancers is tobacco, leading to 18.5 in ASDR and 3.38×107 in DALY for respiratory tract cancers; 8.29 in ASDR and 1.60×107 in DALY for digestive tract cancers, in 2019. Additionally, alcohol use contributes to most digestive and respiratory tract cancers (1.23/1.03 in ASDR and 1.60×106/2.57×106 in DALY for respiratory tract cancers; 4.19/3.82 in ASDR and 4.49×106/8.06×106 in DALY for digestive tract cancers), except for stomach cancer and tracheal, bronchus, and lung cancer. The cancer burdens of respiratory and digestive tracts are likely to decrease substantially between 2020 and 2044. For most metrics, except for the ASIR and male-to-female ratios of ASDR and ASDALY in digestive tract cancers, the worldwide variances of burden metrics have been decreasing in the past decades and will possibly maintain stable trends in the future.

The epidemiology of respiratory and GI tract cancers has common features and individual characteristics that are reflected in geography, age characteristics, and risk factors. Current epidemiological status, future trends, and the globalization of these disease burdens are important factors for making scientific planning of resources to minimize the cancer burden metrics and their cross-regional inequalities.

Tissue biopsy remains the standard for diagnosing gastrointestinal stromal tumors (GISTs), although liquid biopsy is emerging as a promising alternative in oncology. In this pilot study, we advocate for droplet digital PCR (ddPCR) to diagnose GIST in tissue samples and explore its potential for early diagnosis via liquid biopsy, focusing on the PDGFRA D842V mutation and SEPT9 hypermethylated gene. We utilized ddPCR to analyze the predominant PDGFRA mutation (D842V) in surgical tissue samples from 15 GIST patients, correlating with pathologists' diagnoses. We expanded our analysis to plasma samples to compare DNA alterations between tumor tissue and plasma, also investigating SEPT9 gene hypermethylation. We successfully detected the PDGFRA D842V mutation in GIST tissues by ddPCR. Despite various protocols to enhance mutation detection in early-stage disease, it remained challenging, likely due to the low concentration of DNA in plasma samples. Additionally, the results of Area Under the Curve (AUC) for the hypermethylated SEPT9 gene, analyzing concentration, ratio, and abundance were 0.74 (95% Confidence Interval (CI): 0.52 to 0.97), 0.77 (95% CI: 0.56 to 0.98), and 0.79 (95% CI: 0.59 to 0.99), respectively. As a rare disease, the early detection of GIST through such biomarkers is particularly crucial, offering significant potential to improve patient outcomes.

The significance of interstitial cells of Cajal (ICC) in the gastrointestinal tract has garnered increasing attention. In recent years, approximately 80 articles on ICC have been published annually in various journals. However, no bibliometric study has specifically focused on the literature related to ICC. Therefore, we conducted a comprehensive bibliometric analysis of ICC to reveal dynamic scientific developments, assisting researchers in exploring hotspots and emerging trends while gaining a global perspective.

We conducted a literature search in the Web of Science Core Collection (WoSCC) from January 1, 2013, to December 31, 2023, to identify relevant literature on ICC. We employed bibliometric software, namely VOSviewer and CiteSpace, to analyze various aspects including annual publication output, collaborations, research hotspots, current status, and development trends in this domain.

A total of 891 English papers were published in 359 journals by 928 institutions from 57 countries/regions. According to the keyword analysis of the literature, researchers mainly focused on "c-Kit," "expression," "smooth muscle," and "nitric oxide" related to ICC over the past 11 years. However, with "SIP syncytium," "ANO1," "enteric neurons," "gastrointestinal stromal tumors (GIST)," and "functional dyspepsia (FD)," there has been a growing interest in the relationship between ANO1, SIP syncytium, and ICC, as well as the role of ICC in the treatment of GIST and FD.

Bibliometric analysis has revealed the current status of ICC research. The association between ANO1, SIP syncytium, enteric neurons and ICC, as well as the role of ICC in the treatment of GIST versus FD has become the focus of current research. However, further research and collaboration on a global scale are still needed. Our analysis is particularly valuable to researchers in gastroenterology, oncology, and cell biology, providing insights that can guide future research directions.

To investigate the safety and prognosis of enbloc or piecemeal removal after enbloc resection of a gastric GIST by comparing the clinical data of endoscopic en block resection and piecemeal removal (EP) and en block resection and complete removal (EC) of gastric GISTs.

A total of 111 (43 endoscopic piecemeal, and 68 complete removal) patients with gastric GIST's ≥ 2 cm in diameter who underwent endoscopic therapy from January 2016 to June 2020 at the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed. In all cases, it was ensured that the tumor was intact during the resection, however, it was divided into EP group and EC group based on whether the tumor was completely removed or was cut into pieces which were then removed. The patients' recurrence-free survival rate and recurrence-free survival (RFS) were recorded.

There was no statistically significant difference in RFS rates between the two groups (P = 0.197). The EP group had relatively high patient age, tumor diameter, risk classification, and operation time. However, there was no statistically significant difference in the number of nuclear fission images, postoperative hospitalization time, postoperative fasting time, complication rate and complication grading between the two groups (P > 0.05).

Endoscopic piecemeal removal after en block resection of gastric GIST is safe and effective and achieves similar clinical outcomes as complete removal after en block resection.

Cancer treatments have recently shifted from broad-spectrum cytotoxic therapies to more focused treatments, maximizing anticancerous activity while reducing toxicity to healthy cells. These modern anticancer therapies (MATs) encompass a wide range of innovative molecules that include immune checkpoint inhibitors and other targeted anticancer therapies, comprising antibody drug conjugates and inhibitors of signal transduction. Some MATs are associated with ocular surface adverse events that can cause severe discomfort and even lead to loss of vision. While these complications remain rare, they are probably underreported. It is likely that both oncologists and ophthalmologists will come across MATs-associated ocular surface-adverse events in their practices, owing to the increasing number of patients being treated with MATs. Rapid identification of ocular surface-adverse events is crucial, as early intervention can manage these conditions to avoid vision loss and reduce negative impacts on quality of life. We discuss characteristics of ocular surface pathologies attributed to MATs, describe the suspected underlying pathophysiological mechanisms, and outline the main lines of treatment.

For patients with gastrointestinal stromal tumors (GISTs) and liver metastases, there is still debate about whether radiofrequency ablation (RFA) or hepatectomy is preferable. The present study aimed to compare the clinical outcomes of RFA with hepatectomy in patients with GISTs and liver metastases. The present retrospective study consisted of a cohort of 43 patients who had been diagnosed with liver metastases from GISTs between January 2010 and December 2022. The study included 18 patients who received RFA combined with tyrosine kinase inhibitor (TKI) therapy (RFA group) and 25 patients who underwent hepatectomy combined with TKI therapy (hepatectomy group). For the patients with liver metastases, the progression-free survival (PFS) rates at 1, 3 and 5 years were 66.5, 38.2 and 33.9%, respectively. Notably, patients in the hepatectomy group exhibited significantly improved PFS times compared with those in the RFA group (median PFS, 42.7 months vs. 14.3 months; P=0.034). Furthermore, the time to imatinib treatment failure (TTF) was notably improved in the hepatectomy group compared with that in the RFA group, and this difference was statistically significant (median TTF, 71.1 vs. 38.0 months; P=0.041). However, the overall survival (OS) times of patients who received RFA and those who had hepatectomy did not differ significantly (median OS, not reached vs. not reached, P=0.120). There was no statistically significant distinction in PFS and TTF between patients who underwent hepatectomy combined with postoperative TKI and those who underwent hepatectomy combined with perioperative TKI (median PFS, 29.5 vs. not reached; P=0.520; median TTF, 66.4 months vs. 71.1 months; P=0.430). The univariate and multivariate analyses consistently identified the sole prognostic factor affecting PFS as hepatectomy combined with TKI therapy (hazard ratio, 0.379; 95% CI, 0.159-0.899; P=0.028). In conclusion, hepatectomy combined with TKI therapy improved prognosis for patients with liver metastases to a greater extent than RFA combined with TKI therapy. For this type of patient, hepatectomy may be a preferable option.

Gastrointestinal stromal tumor (GIST) is the most common sarcoma located in gastrointestinal tract and derived from the interstitial cell of Cajal (ICC) lineage. Both ICC and GIST cells highly rely on KIT signal pathway. Clinically, about 80-90% of treatment-naive GIST patients harbor primary KIT mutations, and special KIT-targeted TKI, imatinib (IM) showing dramatic efficacy but resistance invariably occur, 90% of them was due to the second resistance mutations emerging within the KIT gene. Although there are multiple variants of KIT mutant which did not show complete uniform biologic characteristics, most of them have high KIT expression level. Notably, the high expression level of KIT gene is not correlated to its gene amplification. Recently, accumulating evidences strongly indicated that the gene coding, epigenetic regulation, and pre- or post- protein translation of KIT mutants in GIST were quite different from that of wild type (WT) KIT. In this review, we elucidate the biologic mechanism of KIT variants and update the underlying mechanism of the expression of KIT gene, which are exclusively regulated in GIST, providing a promising yet evidence-based therapeutic landscape and possible target for the conquer of IM resistance. Video Abstract.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the digestive tract. This study aimed to investigate the clinical characteristics and prognosis of postoperative recurrence or metastasis in patients with low-risk stromal tumors, in order to take individualized postoperative management and treatment for patients with low-risk GISTs with relatively high recurrence.

We retrospectively analyzed the clinicopathological and follow-up data of patients with GISTs who underwent surgical resection in Nanjing Drum Tower Hospital from March 2010 to December 2021. A total of 282 patients with low-risk GISTs were included, none of whom were treated with imatinib. Univariate and multivariate Cox analysis and survival curves were used to explore the relationship between clinical features and recurrence or metastasis in patients with low-risk GISTs.

Of the 282 patients with low-risk GISTs who met inclusion criteria, 14 (4.96%) had recurrence or metastasis. There was a correlation between tumor size, primary site, resection type, Ki67 index, neutrophil lymphocyte ratio (NLR) and CD34 expression and postoperative recurrence or metastasis of GISTs (P < 0.05). Subsequently, multifactorial analysis showed that tumor primary site, tumor size, and Ki67 index were independent risk factors affecting postoperative recurrent or metastasis in patients with low-risk GISTs (P < 0.05). Ultimately, According to Kaplan-Meier analysis, non-gastric primary tumors, larger tumors, and high Ki67 index were significantly associated with poor progression-free survival ( PFS ).

Tumor location, tumor size and Ki-67 were independent risk factors for postoperative recurrence and metastasis in patients with low-risk GISTs. Based on the 2008 modified NIH recurrence risk grading system, combined with the above three factors, it can be used to evaluate the prognosis of patients with low-risk GISTs and provide personalized postoperative review and follow-up management recommendations.

Gastrointestinal Stromal Tumors (GIST) are the most frequent mesenchymal neoplasia of the digestive tract. Genomic alterations in KIT, PDFGRA, SDH, and BRAF genes are essential in GIST oncogenesis. Therefore, the mutations in these genes have demonstrated clinical implications. Tumors with deletions in KIT-exon 11 or duplications in exon 9 are associated with a worse prognosis. In contrast, KIT-exon 11 substitutions and duplications are associated with a better clinical outcome. Moreover, mutations in Kit exon 9 and 11 are actionable, due to their response to imatinib, while mutations in PDGFRA respond to sunitinib and/or avapritinib. Although, molecular testing on tissue samples is effective; it is invasive, requires adequate amounts of tissue, and a long experimental process is needed for results. In contrast, liquid biopsy has been proposed as a simple and non-invasive method to test biomarkers in cancer. The most common molecule analyzed by liquid biopsy is circulating tumor DNA (ctDNA). GISTs ctDNA testing has been demonstrated to be effective in identifying known and novel KIT mutations that were not detected using traditional tissue DNA testing and have been useful in determining progression risk and response to TKI therapy. This allows the clinician to have an accurate picture of the genetic changes of the tumor over time. In this work, we aimed to discuss the implications of mutational testing in clinical outcomes, the methods to test ctDNA and the future challenges in the establishment of alternatives of personalized medicine.

Gastrointestinal stromal tumour (GIST) is a common gastrointestinal sarcoma located in the stromal cells of the digestive tract, and molecular studies have revealed the pathogenesis of mutations in KIT and PDGFRA genes. Since imatinib opened the era of targeted therapy for GIST, tyrosine kinase inhibitors (TKIs) that can treat GIST have been developed successively. However, the lack of new drugs with satisfactory therapeutic standards has made addressing resistance a significant challenge for TKIs in the face of the resistance to first-line and second-line drugs. Therefore, we need to find as many drugs and new treatments that block mutated genes as possible.

We conducted a comprehensive collection of literature using databases, integrated and analysed the selected literature based on keywords and the comprehensive nature of the articles, and finally wrote articles based on the content of the studies.

In this article, we first briefly explained the relationship between GIST and KIT/ PDGFRα and then introduced the related drug treatment. The research progress of TKIs was analyzed according to the resistance of the drugs.

This article describes the research progress of some TKIs and briefly introduces the currently approved TKIs and some drugs under investigation that may have better therapeutic effects, hoping to provide clues to the research of new drugs.

The most prevalent mesenchymal-derived gastrointestinal cancers are gastric stromal tumors (GSTs), which have the highest incidence (60-70%) of all gastrointestinal stromal tumors (GISTs). However, simple and effective diagnostic and screening methods for GST remain a great challenge at home and abroad. This study aimed to build a GST early warning system based on a combination of machine learning algorithms and routine blood, biochemical and tumour marker indicators.

In total, 697 complete samples were collected from four hospitals in Gansu Province, including 42 blood indicators from 318 pretreatment GST patients, 180 samples of gastric polyps and 199 healthy individuals. In this study, three algorithms, gradient boosting machine (GBM), random forest (RF), and logistic regression (LR), were chosen to build GST prediction models for comparison. The performance and stability of the models were evaluated using two different validation techniques: 5-fold cross-validation and external validation. The DeLong test assesses significant differences in AUC values by comparing different ROC curves, the variance and covariance of the AUC value.

The AUC values of both the GBM and RF models were higher than those of the LR model, and this difference was statistically significant (P < 0.05). The GBM model was considered to be the optimal model, as a larger area was enclosed by the ROC curve, and the axes indicated robust model classification performance according to the accepted model discriminant. Finally, the integration of 8 top-ranked blood indices was proven to be able to distinguish GST from gastric polyps and healthy people with sensitivity, specificity and area under the curve of 0.941, 0.807 and 0.951 for the cross-validation set, respectively.

The GBM demonstrated powerful classification performance and was able to rapidly distinguish GST patients from gastric polyps and healthy individuals. This identification system not only provides an innovative strategy for the diagnosis of GST but also enables the exploration of hidden associations between blood parameters and GST for subsequent studies on the prevention and disease surveillance management of GST. The GST discrimination system is available online for free testing of doctors and high-risk groups at https://jzlyc.gsyy.cn/bear/mobile/index.html .

This aim of this study was to investigate the prognostic significance of KIT exon 11 mutation subtypes in patients with GISTs.

A total of 233 consecutive patients diagnosed with GISTs at the First Affiliated Hospital of Zhengzhou University from January 2013 to August 2018 were included in this study. The prevalence and mutation landscape of exon 11 in KIT was presented. The clinicopathological characteristics and prognosis among the different mutation subtypes were analyzed. All the statistical analyses were performed by SPSS22.0.

Somatic mutational analysis indicated that point mutations were the most frequently detected mutations followed by deletions & compound mutations and insertion and tandem duplication mutations in the stomach. Point mutations showed a low mitotic count and a high risk of recurrence, and deletions and compound mutations have a high mitotic count while insertions and tandem duplication mutations showed a low mitotic count with an intermediate recurrence risk. Point mutations and deletions frequently occurred in sequence region codons 550-560 of exon 11, while compound mutations, insertion, and tandem duplication were mainly detected in codons 557-559, 572-580, and 577-581, respectively. The multi-variation analysis demonstrated that tumor diameter and high recurrence risk groups had worse prognostic values. However, mutation types were not significant predictors of relapse-free survival (RFS) in GISTs. Survival analysis suggested no significant difference in RFS between the 557/558 deletion and the other deletions.

This study suggested that mutations in exon 11 of the KIT gene were common with intermediate/high recurrence risk in GISTs patients. Tumor diameter ≥5 cm, and deletions mutations might predict a worse prognosis.

Gastrointestinal stromal tumor (GIST) is rare because of its variable clinical incidence reported (from 0.4 to 2/100,000 per year) in the literature, mainly occurs primarily in the stomach and small intestine. GISTs in the perianal and perineal regions have been reported in a few pieces of literature. GIST located in the perianal and perineal regions may be misdiagnosed and missed due to atypical symptoms. We report two cases of GIST in rare sites and hope to reduce the occurrence of such events through a review of the relevant literature.

We reported two cases of GIST located in the perianal and perineal regions with different symptoms. One case underwent an emergency procedure to stop bleeding and resect the mass, and the other case was discovered during the physical examination and slowly grew in the follow-up. Following the completion of the relevant examination, the patient underwent surgical resection. Both cases were finally diagnosed as GIST by immunohistochemistry.

Due to atypical clinical symptoms of perianal and perineal GIST, definitive diagnosis depends on pathology and immunohistochemistry, which can lead to misdiagnosis and missed diagnosis. Surgical resection is the preferred option for localized masses. Surgical resection of GIST located in the perianal and perineal regions requires an appropriate surgical approach based on the patients' actual condition, taking into account the protection of anal function and complete resection of the mass. Masses located in perianal and perineal region should be taken seriously by clinicians.

Gastrointestinal stromal tumors (GISTs) are rare gastrointestinal neoplasms. We are presenting a 57-year-old female patient with a GIST of considerable dimensions that was deemed unresectable during the initial intervention. The patient had a previous surgical record of a peritoneal sarcomatosis tumor that covered approximately 50% of the abdominal cavity. The patient underwent surgical procedures, including exploratory laparotomy, lumpectomy, splenectomy, proximal gastrectomy, esophagogastric anastomosis, pyloroplasty, jejunostomy, and left diaphragm plasty. One of the observed results was the presence of a 50×40 cm exophytic multilobed cerebroid-like tumor in the abdomen region, specifically dependent on the gastric fundus. The primary treatment for patients without metastases is surgical removal of the tumor, with wedge resection being recommended for the preservation of organ function and quality of life postoperatively.

The study was conducted to investigate the effect of the treatment with imatinib, a c-kit specific inhibitor, on the neointimal hyperplasia (NIH) of aortocaval fistula (ACF) in adenine-induced renal failure rats.

All rats were randomly assigned to 4 groups: rats were fed on a normal diet (normal group); rats were fed on a 0.75% adenine-rich diet (renal failure group). The remaining rats underwent ACF after receiving a 0.75% adenine-rich diet and received daily saline gavage (model group) or imatinib gavage (imatinib group) for 7 days after surgery. Immunohistochemical method was used to detect c-kit expression, and Elastomeric Verhoeff-Van Gieson (EVG) staining was used to observe morphological changes of the ACF. The Pearson correlation analysis was used to evaluate the correlations of c-kit expression with intimal thickness and the percentage of stenosis, respectively.

The renal failure group showed positive c-kit expression on the intima of the inferior vena cava (IVC), whereas the normal group did not. Compared to the model group, intimal thickness (P = 0.001), the percentage of stenosis (P = 0.006) and c-kit expression (P = 0.04) were decreased in the imatinib group at 8 weeks postoperatively. C-kit expression was positively correlated with both intimal thickness and percentage of stenosis (intimal thickness: R = 0.650, P = 0.003; the percentage of stenosis: R = 0.581, P = 0.011) in both the model and imatinib groups.

Treatment with imatinib, a c-kit specific inhibitor, was useful to delay the NIH of ACF in adenine-induced renal failure rats.

Purpose: According to clinical studies, gastrointestinal stromal tumors (GISTs) are predominantly sporadic. GISTs associated with familial syndromes are very rare, and most patients exhibit wild-type KIT and platelet-derived growth factor alpha (PDGFRA). To date, GISTs associated with germline KIT pathogenic variants have been observed in only 30 kindreds worldwide. The efficacy of imatinib, a multityrosine kinase inhibitor, in patients with GIST presenting germline KIT variants has been poorly reported, and the efficacy in clinical trials of treatments with tyrosine kinase inhibitors remains unclear. Therefore, imatinib is not yet recommended for treating GIST patients with germline KIT variants. Experimental Design: We performed cancer genomic testing on samples from a 32-year-old male patient with advanced GISTs throughout the upper stomach and cutaneous hyperpigmentation to determine diagnosis and treatment strategies. Results: We detected a germline W557R pathogenic variant of KIT. The patient was diagnosed with familial multinodular GIST based on the clinical findings and familial history of malignant tumors. Treatment with imatinib resulted in long-term regression of GISTs. Conclusions: Pathogenic variants detected by cancer genome testing can be used to diagnose malignant tumors and select new therapeutic agents for patients with advanced malignancies.

Mesenchymal gastrointestinal cancers are represented by the gastrointestinal stromal tumors (GISTs) which occur throughout the whole gastrointestinal tract, and affect human health and economy globally. Curative surgical resections and tyrosine kinase inhibitors (TKIs) are the main managements for localized GISTs and recurrent/metastatic GISTs, respectively. Despite multi-lines of TKIs treatments prolonged the survival time of recurrent/metastatic GISTs by delaying the relapse and metastasis of the tumor, drug resistance developed quickly and inevitably, and became the huge obstacle for stopping disease progression. Immunotherapy, which is typically represented by immune checkpoint inhibitors (ICIs), has achieved great success in several solid tumors by reactivating the host immune system, and been proposed as an alternative choice for GIST treatment. Substantial efforts have been devoted to the research of immunology and immunotherapy for GIST, and great achievements have been made. Generally, the intratumoral immune cell level and the immune-related gene expressions are influenced by metastasis status, anatomical locations, driver gene mutations of the tumor, and modulated by imatinib therapy. Systemic inflammatory biomarkers are regarded as prognostic indicators of GIST and closely associated with its clinicopathological features. The efficacy of immunotherapy strategies for GIST has been widely explored in pre-clinical cell and mouse models and clinical experiments in human, and some patients did benefit from ICIs. This review comprehensively summarizes the up-to-date advancements of immunology, immunotherapy and research models for GIST, and provides new insights and perspectives for future studies.

The overall risk of cardiovascular mortality (CVM) in cancer survivors has increased with time. The trend of CVM in patients with gastrointestinal stromal tumors (GISTs) remains unclear. This study is aimed at assessing the risks and independent predictors of CVM in GIST patients.

Data of the GIST patients were extracted from the Surveillance, Epidemiology, and End Results (SEER) database (2000-2019). The standardized mortality ratio (SMR) was used to evaluate the risk of CVM, and a multivariate competing risk model was utilized to identify the predictors for CVM.

A total of 12,058 patients with GIST were included in this study, of whom 477 (4.0%) patients died of cardiovascular disease (CVD). The SMR for CVM among GIST patients was significantly higher than in the general population (SMR, 3.23, 95% CI: 2.97-3.52), and all categories of CVD were associated with a significantly elevated SMR. The cumulative mortality of CVD was the lowest among all causes of death, while the CVM was the second most common cause of death in patients ≥ 80 years when stratified by age at diagnosis. Furthermore, male sex, older age at diagnosis, White race, unmarried, earlier year of diagnosis, and not receiving chemotherapy were the poor prognostic factors for CVM.

The CVM risk in GIST patients was significantly higher relative to the general US population. Timely screening and cardioprotective interventions should be implemented to prevent the occurrence of CVM in patients with GIST.

c-Kit protein is a signal transduction protein involved in multiple signal pathways, which play an important role in a variety of cellular events such as cell proliferation, apoptosis and differentiation. Special DNA secondary structures on the promoter of c-Kit gene, including G-quadruplex and i-motif structures, could act as "molecular switch" for gene transcriptional regulation, which are potentially important target for development of new anti-cancer drugs.

We screened and evaluated the effect of compounds on c-Kit through several experiments, including SPR, FRET, CD, MST, NMR, dual-luciferase reporter assay, Western blot, qPCR, immunofluorescence, MTT assay, colony formation, cell scrape, cell apoptosis, cell cycle analysis, and transwell assay.

After extensive screening, we found that bisacridine derivative B05 had selective binding and stabilization to dual i-motif structures on c-Kit gene promoter, which could down-regulate c-Kit gene transcription and translation, resulting in inhibition of cell proliferation and metastasis. B05 exhibited potent anti-tumor activity on HGC-27 cells, and strongly suppressed tumor growth in HGC-27 xenograft mice model.

B05 could interact with c-Kit promoter dual i-motif structures with excellent selectivity, which make it possible for selective regulation of gene transcription and translation. B05 could be further developed for selective anti-cancer agent targeting c-Kit promoter i-motifs.

i-Motifs on different proto-oncogene promoters are diversified, and especially binding of dual i-motifs on the same promoter simultaneously could significantly down-regulate gene transcription with decreased dosage, and therefore increasing the selectivity. This new strategy shed bight light on development of selective DNA-targeting ligands.

Previous studies have confirmed that preoperative nutritional-inflammatory indicators can predict prognosis in various malignancies. However, to the best of our knowledge, no study has investigated the assessment of systemic inflammatory immunity index (SII) combined with prognostic nutritional index (PNI) scores to predict prognosis after neoadjuvant treatment with imatinib in locally advanced gastrointestinal stromal tumours (LA-GIST). The aim of this study was to evaluate the predictive value of pretreatment SII-PNI scores in predicting recurrence after neoadjuvant therapy with imatinib in patients with LA-GIST.

We retrospectively analyzed 57 patients with LA-GIST who received imatinib neoadjuvant from January 2013 to March 2019. Patients were divided into recurrence and non-recurrence groups according to their follow-up status, and SII and PNI cut-offs were calculated by receiver operating characteristic. The SII-PNI score ranged from 0 to 2 and were categorized into the following: score of 2, high SII (≥ 544.6) and low PNI (≤ 47.2); score of 1, either high SII (≥ 544.6) or low PNI (≤ 47.2); score of 0, no high SII (≥ 544.6) nor low PNI (≤ 47.2).

All patients received imatinib neoadjuvant therapy for a median treatment period of 8.5 months (ranging from 3.2 to 12.6 months), with 8 patients (14.04%) and 49 patients (85.96%) developing recurrence and non-recurrence, respectively. Patients with a high SII-PNI score had a significantly worse recurrence-free survival time than those with a low SII-PNI score (P = 0.022, 0.046), and had a poorer pathological response (P = 0.014). Multivariate analysis demonstrated that the SII-PNI score was an independent prognostic factor for prediction of recurrence-free survival (P = 0.002).

The pre-treatment SII-PNI score can be used to predict the efficacy after neoadjuvant treatment with imatinib in patients with LA-GIST, which may be a promising predictor of recurrence-free survival time for patients.

Objective: To construct a simple scoring model for predicting the biological risk of gastrointestinal stromal tumors based on enhanced computed tomography (CT) features. Methods: The clinicopathological and imaging data of 149 patients with primary gastrointestinal stromal tumor were retrospectively analyzed in our hospital. According to the risk classification, the patients were divided into low-risk group and high-risk group. The features of enhanced CT were observed and recorded. Univariate and multivariate logistic regression models were used to determine the predictors of high-risk biological behaviors of gastrointestinal stromal tumor, and then a simple scoring model was constructed according to the regression coefficients of each predictor. The receiver operating characteristic curve was used to evaluate the predictive ability of the model. Results: There was no significant difference between the risk classification of gastrointestinal stromal tumor with gender and age (P = .168, .320), while significant difference was found between the tumor size and location (P < .001). Univariate and multivariate logistic regression analyses showed that tumor size, enlarged vessels feeding or draining the mass, peritumoral lymph node enlargement, and venous phase contrast enhancement rate were independent predictors of the biological risk of gastrointestinal stromal tumor (P < .05). The area under the curve value of tumor size, enlarged vessels feeding or draining the mass, peritumoral lymph node enlargement, and venous phase contrast enhancement rate as the high-risk predictor of gastrointestinal stromal tumor were 0.955, 0.729, 0.680, and 0.807, respectively. Receiver operating characteristic curve results showed that the area under the curve of the scoring model constructed based on enhanced CT features was 0.941 (95% confidence interval: 0.891-0.973). When the total score was >1, the sensitivity of the scoring model in diagnosing gastrointestinal stromal tumor was 85.58%, the specificity was 88.89%, the positive predictive value was 88.51%, the negative predictive value was 86.04%, and the accuracy was 86.18%. The results of DeLong test showed that the area under the curve of the scoring model was better than that of the receiver operating characteristic curve of tumor size, enlarged vessels feeding or draining the mass, peritumoral lymph node enlargement, venous phase contrast enhancement rate, and other indicators alone in predicting the high risk of gastrointestinal stromal tumor, and the differences were statistically significant (Z = 26.510, P < .001; Z = 3.992, P < .001; Z = 6.353, P < .001; Z = 4.052, P = .013). Conclusion: The simple scoring model based on enhanced CT features is a simple and practical clinical prediction model, which is helpful to make preoperative individualized treatment plan and improve the prognosis of gastrointestinal stromal tumor patients.

As one of the most common mesenchymal malignancies in the digestive system, gastrointestinal stromal tumors (GISTs) occur throughout the alimentary tract with diversified oncological characteristics. With the advent of the tyrosine kinase inhibitor era, the treatment regimens of patients with GISTs have been revolutionized and GISTs have become the paradigm of multidisciplinary therapy. However, surgery resection remains recognized as the potentially curative management for the radical resection and provided with favorable oncological outcomes. The existing available surgery algorithms in clinical practice primarily incorporate open procedure, and endoscopic and laparoscopic surgery together with combined operation techniques. The performance of various surgery methods often refers to the consideration of risk evaluation of recurrence and metastases; the degree of disease progression; size, location, and growth pattern of tumor; general conditions of selected patients; and indications and safety profile of various techniques. In the present review, we summarize the fundamental principle of surgery of GISTs based on risk assessment as well as tumor size, location, and degree of progress with an emphasis on the indications, strengths, and limitations of current surgery techniques.

The increasing incidence of gastrointestinal stromal tumors (GISTs) has led to the discovery of more novel prognostic markers. We aim to establish an unsupervised prognostic model for the early prediction of the prognosis of future patients with GISTs and to guide clinical treatment.

We downloaded the GISTs dataset through the cBioPortal website. We extracted clinical information and pathological information, including the microsatellite instability (MSI) score, fraction genome altered (FGA) score, tumor mutational burden (TMB), and copy number alteration burden (CNAB), of patients with GISTs. For survival analysis, we used univariate Cox regression to analyze the contribution of each factor to prognosis and calculated a hazard ratio (HR) and 95% confidence interval (95% CI). For clustering groupings, we used the t-distributed stochastic neighbor embedding (t-SNE) method for data dimensionality reduction. Subsequently, the k-means method was used for clustering analysis.

A total of 395 individuals were included in the study. After dimensionality reduction with t-SNE, all patients were divided into two subgroups. Cluster 1 had worse OS than cluster 2 (HR=3.45, 95% CI, 2.22-5.56, P<0.001). The median MSI score of cluster 1 was 1.09, and the median MSI score of cluster 2 was 0.24, which were significantly different (P<0.001). The FGA score of cluster 1 was 0.28, which was higher than that of cluster 2 (P<0.001). In addition, both the TMB and CNAB of cluster 1 were higher than those of cluster 2, and the P values were less than 0.001.

Based on the CNA of GISTs, patients can be divided into high-risk and low-risk groups. The high-risk group had a higher MSI score, FGA score, TMB and CNAB than the low-risk group. In addition, we established a prognostic nomogram based on the CNA and clinicopathological characteristics of patients with GISTs.

Previous studies have investigated the prognostic value of the Prognostic Nutritional Index (PNI) in patients with gastrointestinal stromal tumours (GISTs). However, the results have been inconsistent. We performed a meta-analysis to quantitatively determine the prognostic and clinicopathological significance of PNI in GISTs.

This meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Pooled HRs and 95% CIs were calculated to estimate the prognostic value of PNI in patients with GISTs. Combined ORs and corresponding 95% CIs were used to evaluate the association between the PNI and clinicopathological characteristics.

The electronic databases PubMed, Web of Science, Embase and Cochrane Library were thoroughly searched from inception to December 2021.

A random-effects model or fixed-effects model was selected based on the level of heterogeneity among the included studies.

Eight studies comprising 2307 patients were included in this meta-analysis. A low PNI was significantly associated with worse recurrence-free survival (RFS) (HR 2.02, 95% CI 1.66 to 2.47, p<0.001) and overall survival (OS) (HR 4.35, 95% CI 1.25 to 16.83, p=0.033) in patients with GISTs. In addition, a low PNI was significantly associated with tumour size ≥5 cm (OR 1.65, 95% CI 1.21 to 2.24, p=0.002) and primary tumour site in small intestine/colorectum/extra-GISTs (OR 2.03, 95% CI 1.26 to 3.26, p=0.004).

Patients with GISTs and a lower PNI had inferior RFS and OS. Patients with GISTs and a low PNI may have a higher risk of tumour recurrence.

Gastrointestinal stromal tumors (GISTs) are potential malignancies that occur in the digestive tract. This study aimed to investigate the risk factors and prognosis of recurrence and metastasis of gastrointestinal stromal tumor (GIST).

From January 2018 to December 2019, 422 patients with GIST who received surgery in the First Affiliated Hospital of Wenzhou Medical University were enrolled. Their clinical data were retrospectively analyzed, and their follow-ups were continued until March 31, 2022. Subsequently, univariate and multivariate Cox analyses, survival curves, and nomograms were adopted to explore the relationship between clinicopathological characteristics and recurrence or metastasis in patients with GIST.

Univariate and multivariate Cox analysis exhibited that the prognosis of patients was affected by tumor rupture (P = 0.040), tumor location (P < 0.001), tumor diameter (P = 0.016), mitotic figures (P < 0.001), and risk grade (P < 0.009). The above variables were selected to create the nomogram for 3-year disease-free survival (DFS). The 3-year the ROC (receiver operating characteristic) curves of the nomogram were (0.878 95% confidence interval [CI]: 0.871-0.939).

Collectively, risk factors affecting postoperative recurrence or metastasis of GIST consist of primary site of tumors, tumor rupture, tumor diameter >10 cm, high-risk tumor classification, and mitotic figures ≥10 per 50 HPFs. And the application of nomogram may help physicians provide individualized diagnosis and treatment for patients with GISTs following surgical resection.

It is urgent to explore the pathogenic mechanism of gastrointestinal stromal tumours (GISTs). KDM6A, a histone demethylase, can activate gene transcription and has not been reported in GISTs. SPARCL1 may serve as a metastasis marker in GIST, but the molecular mechanism remains to be further explored. This study aimed to explore the biological function and molecular mechanism of KDM6A and SPARCL1 in GIST.

CCK-8, live cell count, colony formation, wound-healing and Transwell migration and invasion assays were employed to detect the cell proliferation, migration and invasion. A xenograft model and hepatic metastasis model were used to assess the role of KDM6A and SPARCL1 in vivo.

KDM6A inhibited the proliferation, migration and invasion of GIST cells. Mechanistically, KDM6A promotes the transcription of SPARCL1 by demethylating histone H3 lysine trimethylation and consequently leads to the inactivation of p65. SPARCL1 affected the metastasis of GIST cells in a mesenchymal-epithelial transition- and matrix-metalloproteinase-dependent manner. SPARCL1 knockdown promoted angiogenesis, M2 polarisation and macrophage recruitment by inhibiting the phosphorylation of p65. Moreover, KDM6A and SPARCL1 inhibited hepatic metastasis and macrophage infiltration in vivo.

Our findings establish the critical role of the KDM6A-SPARCL1-p65 axis in restraining the malignancy of GIST.

Malignant primary gastric gastrointestinal stromal tumors (gGISTs) without treatment with imatinib are prone to bleeding and peritoneum implantation during operation. Therefore, preoperative assessment of the malignant potential of gGIST is essential. The use of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) combined with computed tomography (PET/CT) as a non-invasive tool for diagnosis, staging and prognosis evaluation in oncology, may also be useful for gGISTs. In the present study, we analyzed the value of 18F-FDG PET-CT in assessing the malignant potential of gGISTs before treatment.

Patients who were diagnosed with gGIST by pathology and underwent 18F-FDG PET/CT at the same time were collected. The clinicopathological features of 26 patients with gGISTs were retrospectively analyzed at last. The gGIST risk classification was graded according to the US National Institutes of Health (NIH) GIST risk classification criteria [2008]. Lesions were classified as malignant group (moderate- or high-risk category) and benign group (low- or very low-risk category) according to pathology. The relationship between the maximal standard uptake value (SUVmax) and GIST risk category, tumor diameter, Ki-67 index, and mitotic count was analyzed. The cut-off level of SUVmax for the diagnosis of malignant gGIST with the highest sensitivity was calculated based on the receiver-operating characteristic (ROC) curve.

The SUVmax, tumor diameter, Ki-67 index, and mitotic count of the 26 gGIST patients were 5.90±4.49, 7.40±4.92 cm, 7.62%±11.76%, (5.96±3.19)/50 high-power field (HPF), respectively. SUVmax was significantly correlated with GIST risk category, Ki-67 index, and mitotic count (r=0.855, 0.860, and 0.690, all P<0.01) but not with tumor diameter (r=0.383, P=0.054). The SUVmax of gGIST was 7.00±4.57 in the malignant group (moderate or high NIH risk category in 20 patients), which was significantly different from that (2.25±0.77) in the benign group (low or extremely low NIH risk category in 6 patients) (t=4.566, P<0.01). ROC curve analysis showed that a SUVmax cut-off of 2.60 was most sensitive for predicting malignant gGIST. When the area under the curve was 0.967, the sensitivity was 100% and the specificity was 83.3%.

SUVmax may be used as a complementary indicator for predicting the malignant potential of gGISTs before treatment.

KRAS is the most commonly mutated oncogene in human cancers. Targeted therapy and immunotherapy for this gene have made remarkable progress in recent years. However, comprehensive molecular landscape analysis of KRAS in rare tumors is lacking. Retrospective analysis was performed on clinical samples from patients with rare tumors collected between September 2015 and September 2021, using hybrid-capture-based next-generation sequencing for genomic profiling and immunohistochemistry assay for PD-L1. Of the 3,453 patients included in analysis, KRAS mutations were identified in 8.7% patients in overall; mutation rate and mutation subtypes varied widely across tumor systems and subtypes. KRAS mutations included 21 missense mutations, of which G12D (29.2%), G12V (24.6%), and G13D (10.8%) were most common. Interestingly, KRAS G12C was observed in 0.6% patients overall, and in 5.7% of sarcomatoid carcinoma of the lung and 5.4% of clear cell ovarian cancer tumors, but none in small-bowel cancer tumors. 31.8% KRAS mutations and 36.4% KRAS G12C mutations co-occurred with other targetable alterations. No significant correlation was observed between TMB-H, MSI-H, PD-L1 status, and KRAS mutation status, which may be related to the high proportion of G12D. This study is the first KRAS mutation landscape study in rare tumors of large sample size in China and worldwide. Our results suggest that targeted therapy and immunotherapy are both feasible, albeit complex, in these patients. This information may have significant impact on the operation of clinical trials for rare tumor patients with KRAS mutations in China.

Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumours of the digestive system, and complete resection is the only way to provide a radical cure for resectable GISTs. Open surgery and minimally invasive approaches, including laparoscopy, robotic surgery and endoscopy, consist of the mainstream GIST resection. However, there is still a lack of evidence regarding which surgical outcomes and long-term prognosis would be better. Thus, we are planning to conduct a network meta-analysis and systematic review aiming to determine the comparative effectiveness among laparotomy, laparoscopy, endoscopy, robotic surgery, and laparoscopic and endoscopic cooperative surgery in GISTs.

PubMed, EMBASE, the Cochrane Library and Web of Science will be searched for published studies to identify the proper literature comparing open resection, laparoscopy, endoscopy, robotic surgery, and laparoscopic and endoscopic cooperative surgery for resecting GISTs from inception to February 2021. Randomised controlled trials (RCTs) and non-randomised studies comparing at least two different interventions for GIST resection will be included. RCTs and non-randomised studies will be synthesised and analysed separately. Bayesian network meta-analysis will be performed to compare the surgical outcomes and long-term prognosis among the resection methods above. The included studies will be divided into several subgroups according to tumour location and size for further analysis. Sensitivity analysis will be performed to identify and explain heterogeneity to make our results robust. Meta-regression will serve as a supplementary method if data are available. The quality of evidence will be evaluated by the Grading of Recommendations, Assessment, Development and Evaluation.

No ethical approval is required for this network meta-analysis, as it is based on already published data. The findings of the review will be published in a peer-reviewed journal.

CRD42021237892.

Patients with systemic mastocytosis, a dangerous and rare myeloid neoplasm, have long had few therapies available to them and, historically, rarely achieved from significant disease control. However, research and translational developments over the last decade have led to promising new options for disease management. In this review, we briefly outline the history of treatment for systemic mastocytosis and subsequently focus on the clinical development and potential applications of avapritinib (previously known as BLU-285), a potent and selective oral inhibitor of the tyrosine kinase most commonly mutated in this condition.

Phase I data and recent phase II data have demonstrated both safety and efficacy of this agent used as monotherapy, even in patients who have progressed on other targeted therapy. Studies to date have focused on patients with the most aggressive disease, but new trials in indolent mastocytosis are accruing currently. Over the next several years, one may anticipate finalized, peer-reviewed, and formally published data for this agent in both advanced systemic and indolent mastocytosis. Evidence from these early studies will also likely highlight where more research is needed.