Management Of Gastrointestinal Stromal Tumors Research Articles

Gastrointestinal stromal tumours (GIST) in children: An update of this orphan disease

Gastrointestinal stromal tumours (GIST) are tumours of the digestive tract that mainly develop in adults. Recommendations for the management of GIST in pediatrics are limited. We performed an updated review of the literature serving as a basis for the development of diagnostic and therapeutic recommendations for GIST in children and young adults (YA). GIST in pediatric population can have a sporadic presentation but occur more often in a syndromic and/or familial context. Currently more than 170 cases of sporadic GIST or in association with Carney-Stratakis syndrome or Carney's triad family cases of familial GIST have been described in children and YA. These syndromes are frequently associated with germline or somatic alterations in a sub-unit of Succinate Dehydrogenase (SDH). In contrast, the frequency of somatic KIT and PDGFRα oncogene mutations (±15%) is significantly lower as compared to adults with GIST. The recommendations for the management of children with GIST are generally comparable to those used for adult patients, although certain biological differences influence the therapeutic attitude. International collaborations have been deployed in order to increase the clinical and biological knowledge of this orphan pathology in pediatrics.

Gastrointestinal Stromal Tumor (GIST) Quiz: Test your knowledge

Having a strong understanding of the epidemiology, pathophysiology, and clinical management of gastrointestinal stromal tumors (GISTs) is crucial for clinicians who may encounter this cancer. The quiz below is designed for medical students, residents, fellows, and practicing physicians to test their knowledge and review key concepts for understanding GIST.

SP9.8 - Assessing the quality of guidelines for the management of Gastro-Intestinal Stromal Tumour

Abstract Introduction Gastro Intestinal Stromal Tumours (GISTs) are tumours of the gastro-intestinal tract that arise from connective tissue and they have potential for malignancy. A number of guidelines exist in their management. The aim of this study is to assess the quality of these guidelines. Methods A search of the literature was undertaken for appropriate guidelines pertaining to the diagnosis and management of GISTs. The AGREE II checklist was used to assess the current GIST guidelines. Results A total of nine guidelines were included in this study. The overall median score across all guidelines was 68% (lowest; 50%, highest 89%). Guidelines tended to score highly in Domain IV (Clarity of Presentation, median score 76%) as well as Domain VI (Editorial Independence, 67%) and Domain I (Scope and Purpose, 61%). However, lower scores were noted in the Domain V (Applicability, 39%), Domain III (Rigor of Development, 52%) and Domain II (Stakeholder Involvement, 56%). None of the guidelines scored a unanimous ‘Yes’ vote for clinical usage, and all needed some level of modifying. Conclusion Whilst some of the current guidelines for the management of GISTs is of a high quality, there is a need for improvement with regards to the quality of the methodology used to formulate the guidelines and how they can be implemented in daily clinical use.

Patterns of Care and Outcomes of Patients with Small Gastrointestinal Stromal Tumors at a High-Volume Sarcoma Center.

The course of subclinical gastrointestinal stromal tumors (GISTs) is variable. The management of small GISTs is not well-defined. Records of patients presenting with small GISTs with documented follow-up appointment at our institution between 2016 and 2022 were identified and reviewed. Comparative univariate analysis to compare patient and tumor characteristics and outcomes was performed. Eighty-six patients were followed for a median of 3.7 years (range 0.1-20 years). The median size at presentation was 1.7 (range 0.1-2.5) cm. A total of 51.2% (n = 44) underwent surgery before or immediately after initial presentation for pain (18.2%), bleeding (15.9%), or patient preference (6.8%). Another 17.4% (n = 15) had delayed surgery for tumor growth (40%), patient preference (2.7%), bleeding (6.7%), or pain (6.7%). The remaining 31.4% (n = 27) of patients never underwent surgery for reasons that included no growth/stability (44.4%), concomitant cancer diagnosis/treatment (29.6%), comorbidities (14.8%), and patient preference (3.7%). Patients who underwent surveillance without intervention compared with those who had delayed surgery were older (71.1 vs. 60.8 years, p < 0.001) with multiple comorbidities or a concurrent cancer diagnosis (70.3% vs. 20%, p = 0.005). There were no differences in survival or rate of distant metastases. Average time to surgery in the delayed group was 2 (range 0.1-10.3) years, and 86% of these patients underwent surgery by 5.5 years after diagnosis. In older patients with comorbidities or concurrent cancer diagnoses, opting out of surgery does not affect survival. Conversely, younger patients, free from significant comorbidities or other diagnoses, may consider surgery or active surveillance for up to 5 years, with comparable outcomes.

Sunitinib-induced endocapillary proliferative glomerulonephritis with IgA2 deposit in addition to thrombotic microangiopathy: a case report

BackgroundSunitinib, a multi-targeted tyrosine kinase inhibitor, is used as a second-line therapy for gastrointestinal stromal tumors (GIST) resistant to imatinib. However, its impact on the vascular endothelial growth factor (VEGF) pathway can lead to significant toxicities, including hypertension and thrombotic microangiopathy (TMA).Case presentationThis case report describes a unique instance of a patient with metastatic GIST who developed endocapillary proliferative glomerulonephritis (EPGN) with IgA2 deposits and TMA following sunitinib treatment. The patient presented with severe hypertension, nephrotic syndrome, and acute kidney injury. Renal biopsy confirmed the diagnosis, revealing IgA2 deposits, which are not commonly associated with TMA. Discontinuation of sunitinib led to a rapid improvement in renal function and proteinuria. The potential mechanisms underlying sunitinib-induced glomerular injury may involve the blockade of VEGFR-1, affecting immune cell recruitment and function, and the disruption of the nitric oxide and endothelin systems, leading to endothelial damage and immune dysregulation. Management of these toxicities requires a personalized approach, with options ranging from symptomatic relief to drug discontinuation. The use of endothelin receptor antagonists and other therapeutic alternatives for GIST management is discussed.ConclusionsThis case highlights the complex interplay between the therapeutic effects of sunitinib and its potential renal and cardiovascular toxicities, emphasizing the need for close monitoring and effective management strategies to optimize patient outcomes.

Neoadjuvant Imatinib in Gastrointestinal Stromal Tumors (GIST): The First Analysis of a Mexican Population.

Introduction Gastrointestinal stromal tumors (GISTs) are neoplasms originating from the interstitial cells of Cajal, pacemaker cells responsible for intestinal motility. Patients with locally advanced GISTs and those with borderline resections due to the proximity of vital anatomical structures, which could result in unacceptable post-surgical morbidity, require special therapeutic consideration. Imatinib, a tyrosine kinase inhibitor, has demonstrated significant successin the non-surgical management of metastatic GIST, and its favorable impact on overall survival in the adjuvant setting makes it logical to speculate on the benefit it could provide as a neoadjuvant medication in patients with locally advanced disease. Methods Patients aged 18-90 years with a diagnosis of GIST confirmed by immunohistochemistry (CD117 positivity) who were treated at the Oncology Hospital of Centro Médico Nacional Siglo XXI in Mexico City from January 2012 to December 2016 were included in the study. It is a retrospective study with a duration of four years. Clinical data were collected from the medical records, which included sex, age, tumor location, initial resectability, reason for unresectability, initial tumor size, and mitotic rate. In the case of unresectable disease, patients who were evaluated by medical oncology and who had received treatment with 400 mg of imatinib daily were evaluated. Results A total of 312 patients diagnosed with GIST were analyzed. One hundred thirty-one were men (42%) with a mean age of 57 years, and 181 were women (58%) with a mean age of 59 years. The most frequent anatomical location was the stomach (n=185, 59.2%). At the time of diagnosis, 210 patients (67.3%) presented with resectable disease, while n=102 patients (32.7%) had unresectable disease. A total of 102 patients with unresectable disease received therapy with 400 mg of imatinib per day. Sixteen patients (15.7%) presented a reduction in tumor dimensions and underwent surgery. Conclusion The study highlights the importance of complete surgical resection and the potential benefit of neoadjuvant imatinib therapy in converting unresectable to resectable disease. The results suggest that imatinib can be effective in converting unresectable GISTs to resectable ones, allowing for a complete resection to be performed and obtaining an R0 resection in 93.7% of these cases.

Surgical management of gastrointestinal stromal tumors of gastric origin

Gastrointestinal Stromal Tumors (GISTs) account for 1 to 2% of gastrointestinal malignant tumors. They are characterized by overexpression of the tyrosine kinase (KIT). 60% of GISTs originate in the stomach. Managing them remains complex and varies depending on several factors such as location, size, molecular biology, type of clinical presentation, and the risks/benefits of surgical treatment. Surgery remains the only curative treatment, while tyrosine kinase inhibitors have demonstrated their efficacy as systemic treatment in the perioperative context. Risk stratification for recurrence guides the choice of adjuvant treatment, with a recommended duration of 3 years for high-risk patients.

The GIST of it all: management of gastrointestinal stromal tumors (GIST) from the first steps to tailored therapy. A bibliometric analysis

PurposeImprovement of patient care is associated with increasing publication numbers in biomedical research. However, such increasing numbers of publications make it challenging for physicians and scientists to screen and process the literature of their respective fields. In this study, we present a comprehensive bibliometric analysis of the evolution of gastrointestinal stromal tumor (GIST) research, analyzing the current state of the field and identifying key open questions going beyond the recent advantages for future studies to assess.MethodsUsing the Web of Science Core Collection, 5040 GIST-associated publications in the years 1984–2022 were identified and analyzed regarding key bibliometric variables using the Bibliometrix R package and VOSviewer software.ResultsGIST-associated publication numbers substantially increased over time, accentuated from year 2000 onwards, and being characterized by multinational collaborations. The main topic clusters comprise surgical management, tyrosine kinase inhibitor (TKI) development/treatment, diagnostic workup, and molecular pathophysiology. Within all main topic clusters, a significant progress is reflected by the literature over the years. This progress ranges from conventional open surgical techniques over minimally invasive, including robotic and endoscopic, resection techniques to increasing identification of specific functional genetic aberrations sensitizing for newly developed TKIs being extensively investigated in clinical studies and implemented in GIST treatment guidelines. However, especially in locally advanced, recurrent, and metastatic disease stages, surgery-related questions and certain specific questions concerning (further-line) TKI treatment resistance were infrequently addressed.ConclusionIncreasing GIST-related publication numbers reflect a continuous progress in the major topic clusters of the GIST research field. Especially in advanced disease stages, questions related to the interplay between surgical approaches and TKI treatment sensitivity should be addressed in future studies.

A new green fluorimetric micelle complexation approach for reduction of the consumed solvent and quantification of avapritinib in biological fluids.

Avapritinib (AVA) is the first medication authorized by the US-FDA in 2020 for the management of gastrointestinal stromal tumours (GISTs) that can't be treated by surgery. Cancer is among the most common causes of death worldwide and is the second most common cause of death after cardiovascular disease. Therefore, a quick, easy, sensitive, and straightforward fluorimetric approach was used to analyse AVA in pharmaceutical materials and blood plasma (pharmacokinetic). The suggested technique relies on 2% sodium dodecyl sulphate (SDS, pH 4) micellar system augmentation of the fluorescence of the tested drug. The technique demonstrated high relative fluorescence intensity (RFI) at 430 nm after excitation at 340 nm. Concentrations ranging from 20.0-400.0 ng mL-1 with a limit of quantitation of 9.47 ng mL-1 were used to obtain luminescence data for the studied medicine. In addition, the quantum yield of the AVA fluorescence was increased with the gradual addition of a surfactant at a concentration above its critical micellar level. This knowledge has been exploited to enhance the effectiveness of a spectrofluorometric technique for the estimation of AVA in human plasma (98.95 ± 1.22%) and uniformity tests with greenness assessments. The conditions for enhanced fluorescence were optimized and fully validated using US-FDA and International Conference on Harmonization (ICH) rules. This innovative strategy was expanded for AVA stability research in human plasma across various circumstances. This approach is an eco-friendly solution compared to traditional testing methods that use hazardous chemicals.

Pan-Canadian consensus recommendations for GIST management in high- and low-throughput centres across Canada.

Gastrointestinal stromal tumours (GISTs) are mesenchymal tumours that originate from the interstitial cells of Cajal. GISTs are mainly driven by gain-of-function mutations in receptor tyrosine kinase or platelet-derived growth factor receptor alpha. Surgical resection is the only curative treatment for localized tumours and all currently approved medical GIST treatments are based on orally available tyrosine kinase inhibitors. Recent discoveries in the molecular and clinical features of GISTs have greatly impacted GIST management. Due to the provincially rather than nationally administered Canadian healthcare system, there have been inconsistencies in the treatment of GISTs across the country. Therefore, guidance on the latest knowledge, clinical management and treatment of GIST is needed to standardize the approach to GIST management nationwide. To establish pan-Canadian guidance, provide up-to-date data and harmonize the clinical practice of GIST management in high- and low-throughput centres across Canada; a panel of 20 physicians with extensive clinical experience in GIST management reviewed relevant literature. This included radiologists, pathologists, interventional radiologists, surgeons and medical oncologists across Canada. The structured literature focused on seven key domains: molecular profiling, radiological techniques/reporting, targeted localized therapy, intricacies of systemic treatments, emerging tests, multidisciplinary care and patient advocacy. This literature review, along with clinical expertise and opinion, was used to develop this concise and clinically relevant consensus paper to harmonize the knowledge and clinical practice on GIST management across Canada. The content presented here will help guide healthcare providers, especially in Canada, in terms of approaching and managing GIST.

Understanding and Addressing the Challenges of Gastrointestinal Stromal Tumor (GIST): Towards Improved Diagnosis and Treatment Strategies

Gastrointestinal stromal tumor (GIST) is a prevalent mesenchymal tumor affecting the digestive tract, with the stomach being the most common location. While some GIST cases are sporadic with no known risk factors, certain factors like age and genetic abnormalities increase the risk. Early diagnosis of GIST remains challenging due to atypical symptoms, leading to late diagnoses and reduced survival rates. This research aims to identify specific risk factors related to local populations, develop accurate early diagnosis methods, and formulate more effective treatment strategies. The study involves a retrospective observational approach, collecting data from medical records of GIST patients and analyzing risk factors and treatment outcomes. The results highlight the increasing prevalence of GIST globally, emphasizing the need for increased awareness and early diagnosis. Challenges in early diagnosis and treatment underscore the importance of public awareness, medical education, and collaborative efforts for better GIST management. This research offers implications for the development of diagnostic guidelines and more effective treatment approaches, ultimately improving the prognosis and quality of life for GIST patients.

Gastrointestinal Stromal Tumor (GIST)

&#x0D; &#x0D; &#x0D; Gastrointestinal stromal tumor (GIST) are the most common mesenchymal tumor of the gastrointestinal tract and most common malignancy of the small intestine. Although the exact prevalence of GIST is not known, GIST was recognized as tumor it's arise from interstitial cells of Cajal. Most of the GISTs driven by a KIT or platelet-derived growth factor receptor alpha (PDGFRA) mutation. Histologically, GISTs look like spindle cell tumors most of the time, but they can be epitheoid or mixed type. Clinically, patients with small GISTs remain asymptomatic. In another case, patients with larger GISTs present with various symptoms depending on the location of the GISTs. Most of GISTs are located in the stomach or small bowel. But, they can involve almost any segment of the gastrointestinal tract from distal esophagus to anus. Diagnosis is suspected on imaging and endoscopic studies, and confirmed by tissue acquisition with immunohistochemical staining. The various endoscopic modalities of resection are increasingly tried. Surgical resection is the treatment of choice. In management of larger GISTs, tyrosine kinase inhibitors are extremly useful. Treatment options for metastatic GISTs also include radiotherapy, chemotherapy, hepatic artery embolization, chemoembolization, and radiofrequency ablation.&#x0D; &#x0D; &#x0D;

CT and MRI of Gastrointestinal Stromal Tumors: New Trends and Perspectives.

Gastrointestinal stromal tumors (GISTs) are defined as mesenchymal tumors of the gastrointestinal tract that express positivity for CD117, which is a c-KIT proto-oncogene antigen. Expression of the c-KIT protein, a tyrosine kinase growth factor receptor, allows the distinction between GISTs and other mesenchymal tumors such as leiomyoma, leiomyosarcoma, schwannoma and neurofibroma. GISTs can develop anywhere in the gastrointestinal tract, as well as in the mesentery and omentum. Over the years, the management of GISTs has improved due to a better knowledge of their behaviors and risk or recurrence, the identification of specific mutations and the use of targeted therapies. This has resulted in a better prognosis for patients with GISTs. In parallel, imaging of GISTs has been revolutionized by tremendous progress in the field of detection, characterization, survival prediction and monitoring during therapy. Recently, a particular attention has been given to radiomics for the characterization of GISTs using analysis of quantitative imaging features. In addition, radiomics has currently many applications that are developed in conjunction with artificial intelligence with the aim of better characterizing GISTs and providing a more precise assessment of tumor burden. This article sums up recent advances in computed tomography and magnetic resonance imaging of GISTs in the field of image/data acquisition, tumor detection, tumor characterization, treatment response evaluation, and preoperative planning.

The past, present, and future: the evolving role and challenges of surgery in the multimodal management of gastrointestinal stromal tumors

The past, present, and future: the evolving role and challenges of surgery in the multimodal management of gastrointestinal stromal tumors

Progress in the Treatment of Small Intestine Cancer.

Small intestine cancer is rare, accounting for approximately 3% of all gastrointestinal malignancies. The most common histological subtypes include adenocarcinoma, neuroendocrine tumours (NETs) and gastrointestinal stromal tumours (GISTs). In localised disease, surgery remains the mainstay of treatment and the best approach to improve survival. Current treatment for small intestine adenocarcinoma (SIA) is extrapolated from small studies and data from colorectal cancer (CRC). There is limited evidence to guide therapy in the adjuvant setting. However, there are small phase II studies in the advanced setting providing evidence for the role of chemotherapy and immunotherapy. There is also limited evidence assessing the efficacy of targeted therapies. Small intestine NETs are rare, with evidence for somatostatin analogue therapy, particularly in the low to intermediate-grade well-differentiated tumours. Poorly differentiated NETs are generally managed with chemotherapy but have worse outcomes compared with well-differentiated NETs. The management of small intestine GISTs is largely targeting KIT mutations with imatinib. Recent trials have provided evidence for effective therapies in imatinib-resistant tumours and the potential role of immunotherapy. The aim of this article was to review the evidence for the current management and recent advances in the management of small intestine adenocarcinoma, NETs and GISTs.

Insights into the medical management of gastrointestinal stromal tumours: lessons learnt from a dedicated gastrointestinal stromal tumour clinic in North India.

The advent of molecular driver alterations has brought in a revolutionary transformation in the treatment landscape of gastrointestinal stromal tumour (GIST). However, there is a paucity of data regarding mutational testing prevalence and associated outcomes from India. It was a retrospective study. We reviewed the case records of all patients diagnosed with GIST in a tertiary care centre from 2015 to 2021. The clinicopathological, mutational analysis and treatment plans were recorded. The study cohort was characterised by descriptive statistics. Our study included 120 patients with a median age of 53 years (range: 28-77), with a male preponderance of 2:1. The most common site of the primary was the stomach (50%), followed by the small intestine (37%), with 55.8% of the patients having disseminated disease at presentation with a predominance of liver metastasis (67%). The prevalence of mutational analysis among patients prior to referral was 4%. 60.8% of the patients at our clinic had mutational analysis performed, and unavailability of analysis in the rest was due to financial constraints (12.5%), exhaustion of tissue (7.5%), reluctance to repeat biopsy (4.1%) and low-risk patients. We report c-kit in the majority (52%), platelet-derived growth factor receptor (PDGFR) in 19.2% and wild type in 16.4% along with the rarer subtypes: succinate dehydrogenase (SDH)-deficient GIST in 10.9% and Neurotrophic tyrosine receptor kinase (NTRK) fusion in 1.3%. Four of the eight SDH-deficient GIST patients had germline mutations (50%). The knowledge of driver mutations led to a change of treatment in 39.7% (29/73), i.e. stoppage of tyrosine kinase inhibitor (TKI) in 3, switch of TKI in 23, increase in TKI dose in 2 and upfront surgery in 1. The most common change was the use of sunitinib and regorafenib in patients with SDH-deficient GIST. Our study is one of the largest comprehensive series describing the clinical and mutational profile of GIST from India. The mutation testing rates at primary care centres continue to be low. Despite the hurdles, a large percentage of our patients underwent molecular testing, aiding in therapeutic decision-making.

Artificial intelligence in endoscopic ultrasonography: risk stratification of gastric gastrointestinal stromal tumors.

Previous studies have identified useful endoscopic ultrasonography (EUS) features to predict the malignant potential of gastrointestinal stromal tumors (GISTs). However, the results of the studies were not consistent. Artificial intelligence (AI) has shown promising results in medicine. We aimed to build a risk stratification EUS-AI model to predict the malignancy potential of GISTs. This was a retrospective study with external validation. We developed two models using EUS images from two hospitals to predict the GIST risk category. Model 1 was the four-category risk EUS-AI model, and Model 2 was the two-category risk EUS-AI model. The diagnostic performance of the models was validated with external cohorts. A total of 1320 images (880 were very low-risk, 269 were low-risk, 68 were intermediate-risk, and 103 were high-risk) were finally chosen for building the models and test sets, and a total of 656 images (211 were very low-risk, 266 were low-risk, 88 were intermediate-risk, and 91 were high-risk) were chosen for external validation. The overall accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for the four-category risk EUS-AI model in the external validation sets by tumor were 74.50%, 55.00%, 79.05%, 53.49%, and 81.63%, respectively. The accuracy, sensitivity, specificity, PPV, and NPV for the two-category risk EUS-AI model for the prediction of very low-risk GISTs in the external validation sets by tumor were 86.25%, 94.44%, 79.55%, 79.07%, and 94.59%, respectively. We developed a EUS-AI model for the risk stratification of GISTs with promising results, which may complement current clinical practice in the management of GISTs. The study has been registered in the Chinese Clinical Trial Registry (No. ChiCTR2100051191).

2023 GEIS Guidelines for gastrointestinal stromal tumors.

Gastrointestinal stromal tumor (GIST) is the most common malignant neoplasm of mesenchymal origin. GIST spans a wide clinical spectrum that ranges from tumors with essentially no metastatic potential to malignant and life-threatening spread diseases. Gain-of-function mutations in KIT or PDGFRA receptor tyrosine kinases are the crucial drivers of most GISTs, responsible for tumor initiation and evolution throughout the entire course of the disease. The introduction of tyrosine kinase inhibitors targeting these receptors has substantially improved the outcomes in this formerly chemoresistant cancer. As of today, five agents hold regulatory approval for the treatment of GIST: imatinib, sunitinib, regorafenib, ripretinib, and avapritinib. This, in turn, represents a success for a rare neoplasm. During the past two decades, GIST has become a paradigmatic model in cancer for multidisciplinary work, given the disease-specific particularities regarding tumor biology and tumor evolution. Herein, we review currently available evidence for the management of GIST. This clinical practice guideline has been developed by a multidisciplinary expert panel (oncologist, pathologist, surgeon, molecular biologist, radiologist, and representative of patients' advocacy groups) from the Spanish Group for Sarcoma Research, and it is conceived to provide, from a critical perspective, the standard approach for diagnosis, treatment, and follow-up.

Gastrointestinal Stromal Tumours (GIST) of the Rectum: A Systematic Review and Meta-Analysis.

Rectal gastrointestinal stromal tumours (GISTs) have many treatment options, but uncertainty remains regarding the best treatment regimen for this rare pathology. The aim of this review is to assess the optimal management approach including timing of chemotherapy. PubMed, EMBASE, and Cochrane databases were searched for relevant articles comparing the impact of radical vs. local excision, and neoadjuvant vs. adjuvant therapy had on outcomes in the management of rectal GISTs. We specifically evaluated the influence that the aforementioned factors had on margins, recurrence, overall survival, 5-year disease-free survival, and hospital length of stay. Twenty-eight studies met our predefined criteria and were included in our study, twelve of which were included in the quantitative synthesis. When comparing neoadjuvant versus adjuvant chemotherapy, our meta-analysis noted no significance in terms of margin negativity (R0) (odds ratio [OR] 2.01, 95% confidence interval [CI], 0.7-5.79, p = 0.20) or recurrence rates (OR 0.22, 95% CI, 0.02-1.91, p = 0.17). However, there was a difference in overall 5-year survival in favour of neoadjuvant therapy (OR 3.19, 95% CI, 1.37-7.40, * p = 0.007). Comparing local excision versus radical excision, our meta-analysis observed no significance in terms of overall 5-year survival (OR1.31, 95% CI, 0.81-2.12, p = 0.26), recurrence (OR 0.67, 95% CI, 0.40-1.13, p = 0.12), or 5-year disease-free survival (OR 1.10, 95% CI, 0.55-2.19, p = 0.80). There was a difference in length of hospital stay with a reduced mean length of stay in local excision group (mean difference [MD] 6.74 days less in the LE group; 95% CI, -6.92--6.56, * p =&lt; 0.00001) as well as a difference in R0 rates in favour of radical resection (OR 0.68, 95% CI, 0.47-0.99, * p = 0.05). Neoadjuvant chemotherapy is associated with improved overall 5-year survival, while local excision is associated with reduced mean length of hospital stay. Further large-volume, prospective studies are required to further define the optimal treatment regimen in this complex pathology.

Small Gastric Stromal Tumors: An Underestimated Risk

Small gastrointestinal stromal tumors (GISTs) are defined as tumors less than 2 cm in diameter, which are often found incidentally during gastroscopy. There is controversy regarding the management of small GISTs, and a certain percentage of small GISTs become malignant during follow-up. Previous studies which used Sanger targeted sequencing have shown that the mutation rate of small GISTs is significantly lower than that of large tumors. The aim of this study was to investigate the overall mutational profile of small GISTs, including those of wild-type tumors, using whole-exome sequencing (WES) and Sanger sequencing. Thirty-six paired small GIST specimens, which were resected by endoscopy, were analyzed by WES. Somatic mutations identified by WES were confirmed by Sanger sequencing. Sanger sequencing was performed in an additional 38 small gastric stromal tumor samples for examining hotspot mutations in KIT, PDGFRA, and BRAF. Somatic C-KIT/PDGFRA mutations accounted for 81% of the mutations, including three novel mutation sites in C-KIT at exon 11, across the entire small gastric stromal tumor cohort (n = 74). In addition, 15% of small GISTs harbored previously undescribed BRAF-V600E hotspot mutations. No significant correlation was observed among the genotype, pathological features, and clinical classification. Our data revealed a high overall mutation rate (~96%) in small GISTs, indicating that genetic alterations are common events in early GIST generation. We also identified a high frequency of oncogenic BRAF-V600E mutations (15%) in small GISTs, which has not been previously reported.