Preoperative CT-Based Deep Learning Model for Predicting Risk Stratification in Patients With Gastrointestinal Stromal Tumors

ObjectiveTo develop and evaluate a deep learning model (DLM) for predicting the risk stratification of gastrointestinal stromal tumors (GISTs).MethodsPreoperative contrast-enhanced CT images of 733 patients with GISTs were retrospectively obtained from two centers between January 2011 and June 2020. The datasets were split into training (n = 241), testing (n = 104), and external validation cohorts (n = 388). A DLM for predicting the risk stratification of GISTs was developed using a convolutional neural network and evaluated in the testing and external validation cohorts. The performance of the DLM was compared with that of radiomics model by using the area under the receiver operating characteristic curves (AUROCs) and the Obuchowski index. The attention area of the DLM was visualized as a heatmap by gradient-weighted class activation mapping.ResultsIn the testing cohort, the DLM had AUROCs of 0.90 (95% confidence interval [CI]: 0.84, 0.96), 0.80 (95% CI: 0.72, 0.88), and 0.89 (95% CI: 0.83, 0.95) for low-malignant, intermediate-malignant, and high-malignant GISTs, respectively. In the external validation cohort, the AUROCs of the DLM were 0.87 (95% CI: 0.83, 0.91), 0.64 (95% CI: 0.60, 0.68), and 0.85 (95% CI: 0.81, 0.89) for low-malignant, intermediate-malignant, and high-malignant GISTs, respectively. The DLM (Obuchowski index: training, 0.84; external validation, 0.79) outperformed the radiomics model (Obuchowski index: training, 0.77; external validation, 0.77) for predicting risk stratification of GISTs. The relevant subregions were successfully highlighted with attention heatmap on the CT images for further clinical review.ConclusionThe DLM showed good performance for predicting the risk stratification of GISTs using CT images and achieved better performance than that of radiomics model.

Laparoscopic resection of small bowel gist: a case report

Small bowel bleed accounts for approximately 5% of all gastrointestinal bleeding. While arteriovenous malformation is the commonest cause of small bowel bleeding, other causes include inflammatory bowel disease, small bowel tumours, ulcers and polyps make up the rest. Tumours range from benign adenomas, hamartomas and leiomyomas to malignant GISTs, adenocarcinomas or lymphomas. We reported a case of a jejunal GIST causing intermittent bleeding. Upper and lower GI endoscopy did not find any abnormality and the diagnosis was made through computerized tomography. It showed a mid-jejunal tumour that was in close proximity to the distal duodenum. The rest of the hollow and solid organs were normal. The patient was prepared and underwent laparoscopic assessment. The tumour was mobile, arising from proximal jejunum and did not show infiltration or adhesions to nearby viscera. A segmental resection with adequate margin was performed laparoscopically and extracted through the umbilical port wound. The pathology report revealed an intermediate GIST with clear margins. Laparoscopic assessment should ideally be carried prior to any resection of small bowel tumours. Uncomplicated small bowel resections can safely be done laparoscopically with good oncological outcome and faster patient recovery.

Submucosal gastric lesions: a CECT-based tool for differential diagnosis between gastrointestinal stromal tumor and leiomyoma

Aim. To identify criteria for differential diagnosis between gastrointestinal stromal tumor (GIST) and gastric leiomyoma (GLe) in contrast-enhanced computed tomography (CECT).Material and methods. We retrospectively analyzed CECT data of 65 patients with GIST and 19 patients with GLe. All cases were histologically and immunohistochemically proved. We evaluated tumor size, contours, growth type, extraorgan extension, invasion into the surrounding tissues, tumor calcification/ulceration/necrosis and regional lymph node status.Results. Among 84 patients divided into two groups (65 patients with GIST and 19 with GLe, respectively) we found that tumor localization, heterogeneous enhancement, and intratumoral necrosis may be utilized for differential diagnosis. The prognostic value significantly increased with the use of relative density ratio (tumor density/ aorta density or tumor density/portal vein density in the arterial, venous, and delayed phases, respectively) compared to tumor density alone. It was found that malignant GISTs are characterized by a higher relative density ratio than leiomyomas in the venous phase.Conclusion. We developed a prognostic model for differential diagnosis between GIST and GLe with a sensitivity of 90.8% and specificity of 89.5%. We created an online calculator that preoperatively determines probable tumor type (http://medstatistic.ru/giso.html).

Low ETV1 mRNA expression is associated with recurrence in gastrointestinal stromal tumors

Although the majority of gastrointestinal stromal tumors (GISTs) possess KIT mutations that induce constitutive signal transduction, the clinical outcomes are variable. The ETS translocation variant 1 (ETV1) gene encodes a transcription factor that is reported to cooperate with KIT in GISTs. However, the clinical role of ETV1 is largely unknown. The aim of this study was to examine ETV1 expression and its associations with clinical features in GISTs. We conducted a cohort study involving 64 patients with GISTs who underwent surgical resection between October 2008 and February 2015. ETV1 mRNA expression was compared with that in non-GISTs and was analyzed among risk classifications or clinical outcomes. The GIST samples exhibited significantly higher ETV1 mRNA expression than the non-GIST samples (P < 0.0001). Sixty-four GISTs were stratified into high or low ETV1 mRNA expression groups based on the median relative abundance of ETV1 mRNA. The multivariate analysis showed that low ETV1 expression, as well as tumor size and mitotic index, was an independent factor of recurrence (hazard ratio: 8.1). Patients with high ETV1 expression achieved significantly longer recurrence-free survival (RFS) times than those with low ETV1 expression (P = 0.025). Our study revealed that low ETV1 expression is an independent factor of recurrence after surgery in patients with GISTs, and thus, low ETV1 expression might be a marker of more aggressive malignant GISTs.

Gastrointestinal and Extra-Gastrointestinal Stromal Tumours: A Clinicopathological and Immunohistochemical (c-KIT) Study

Introduction: Gastrointestinal Stromal Tumour (GIST) is one of the most common mesenchymal tumours of GIT. They have been proved to be arising from the smooth muscle pacemaker interstitial cells of Cajal, these cells are involved in gut motility and peristaltic movements. They can also rarely arise outside the Gastrointestinal Tract (GIT) from retroperitoneum, mesentery and omentum called as Extragastrointestinal Stromal Tumor (EGIST). Single best defining feature of GIST is positivity for Cytoplasmic Tyrosine Kinase (c-KIT). Aim: The aim of the study was to analyse clinicopathological features and c-KIT expression in both gastrointestinal and EGISTs. Materials and Methods: This was a retrospective observational (cohort) study; over a period of two years from January 2018 to December 2019, done at Navodaya Medical College and Hospital, Raichur, Karnataka, which comprised of 12 cases of GIST. All the cases were a resected specimens and thorough evaluation of clinical, imaging and histopathological studies were done and forwarded for immunohistochemistry for c-KIT expression. Results: Age of cases ranged from 04-70 years, mean age being 50.6 years and male to female ratio 2:1. Presenting symptoms of most of GIST were pain abdomen, diarrhea and few with vomiting whereas, rectosigmoid GISTs (2 cases and one with metastasis to liver) were associated with pain abdomen, bleeding per rectum and constipation. One case of retroperitoneal (extraintestinal) GIST was asymptomatic and other presented with pain in the right hip due to secondaries and one benign gastric serosal GIST was associated with gastric adenocarcinoma. The CT scan in two of malignant GISTs, confirmed metastasis and c-KIT study was negative in these 2 malignant GISTs. Conclusion: This study reaffirms importance of CD117 in diagnosis of GIST and EGIST, however, the negativity of CD117 does not rule out GIST, which requires thorough clinico-radiological and pathological correlation.

A Malignant Gastrointestinal Stromal Tumor of the Gallbladder Immunoreactive for PDGFRA and Negative for CD 117 Antigen (c-KIT)

Gastrointestinal stromal tumors (GISTs) compose the largest category of well-recognized nonepithelial neoplasms of the gastrointestinal tract (GI). GISTs of the gallbladder are extremely rare tumors. Only four malignant, two benign and one GIST-like tumor of the gall bladder have ever been described. The four malignant GISTs were all positive for CD 117 antigen (c-kit). We present for the first time a malignant gastrointestinal stromal tumor of the gallbladder, immunoreactive for platelet-derived growth factor receptor alpha (PDGFRA) and negative for CD 117 antigen (c-KIT).

The Efficacy of Imatinib in Unresectable/Metastatic Gastrointestinal Stromal Tumors

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal malignancy in the gastrointestinal tract. Their pathogenesis is largely based on gain-of-function mutations in the c-kitproto-oncogene, resulting in constitutive activation of the KIT receptor tyrosine kinase. Historically, there were limited options for the medical management of GIST, with tumor recurrence frequently observed following complete surgical resection of primary localized GIST and a grim prognosis for patients with unresectable or metastatic disease. However, the introduction of the tyrosine kinase inhibitor (TKI) imatinib mesylate has had a major impact on treatment outcomes for these patients with GIST. Imatinib is currently approved for the treatment of patients with KIT/CD117-positive unresectable and/or metastatic malignant GISTs. Initial therapy with the conventional 400mg/day dose is highly recommended in these patients, while a higher dose (800mg/day) has shown promise in patients who have KIT exon 9-mutant GIST and those who experience disease progression on the conventional dose. Neoadjuvant therapy has also been shown to be safe and beneficial as a palliative treatment.

The Role of Imatinib Following Complete Resection of Primary Gastrointestinal Stromal Tumors

Gastrointestinal stromal tumor (GIST) is a life-threatening disease, for which surgery is the standard of care. However, surgical resection of the primary tumor is associated with a high rate of recurrence and a low five-year overall survival (OS) rate. The introduction of the KIT protein kinase-targeted therapy imatinib mesylate has enhanced treatment options. It has demonstrated improvements in progression-free survival and OS in patients with unresectable and/or metastatic malignant GISTs. Based on this efficacy, imatinib has been evaluated as an adjuvant option in KIT-positive primary GIST patients who have undergone complete gross resection. Early data indicate that one-year adjuvant therapy with imatinib 400mg/day can prolong recurrence-free survival (RFS) in these patients. Preliminary data also indicate potential benefits of a higher imatinib dose (800mg/day) and a longer duration of adjuvant imatinib therapy. Currently, imatinib, at a recommended dose of 400mg/day, is approved by the US Food and Drug Administration (FDA) as an adjuvant therapy in adult patients who have undergone complete gross resection of KIT-positive GIST.

Distinct Gene Expression–Defined Classes of Gastrointestinal Stromal Tumor

Purpose The majority of gastrointestinal stromal tumors (GIST) can be cured by surgery alone, but relapse occurs in 20% to 40% of cases. GISTs are considered to invariably arise through gain of function KIT or PDGFA mutation of the interstitial cells of Cajal (ICC). However, the genetic basis of the malignant progression of GISTs are poorly understood. Patients and Methods The expression levels of 54,613 probe sets in 32 surgical samples of untreated GISTs of the stomach and small intestine were analyzed with oligonucleotide microarrays. The representative GeneChip data were validated by real-time reverse transcriptase polymerase chain reaction and immunohistochemistry. Results Unbiased hierarchical clustering consistently separated the 32 cases of GIST into two major classes according to tumor site. The two major classes were further separated into novel subclasses, which were significantly correlated with various pathological prognostic parameters, the frequency of metastasis (P < .05), and clinical outcome. Immunohistochemical analysis of 152 independent patients with gastric GISTs revealed that the expression of dipeptidyl peptidase IV (T-cell activation antigen CD26) protein was significantly associated with poorer overall and disease-free survival (P < .00001). Conclusion CD26 appears to be a reliable biomarker of malignant GISTs of the stomach. The postoperative recurrence rate of CD26-negative cases was as low as 2.0% (two of 102). Therefore, postoperative follow-up of such patients might be made less intensive. CD26 may play an important role in the malignant progression of gastric GISTs and serve as a therapeutic target.