Gastrointestinal Stromal Tumors Research Articles

Financial difficulties experienced by patients with gastrointestinal stromal tumours (GIST) in the Netherlands: data from a cross-sectional multicentre study

PurposeThis study aims to (1) explore the prevalence of patient-reported financial difficulties among GIST patients, differentiating between those currently undergoing tyrosine kinase inhibitor (TKI) treatment and those who are not; (2) investigate associations between financial difficulties and sociodemographic and clinical characteristics, work, cancer-related concerns, anxiety and depression and (3) study the impact of financial difficulties on health-related quality of life.MethodsA cross-sectional study was conducted among Dutch GIST patients diagnosed between 2008 and 2018, who were invited to complete a one-time survey between September 2020 and June 2021. Patients completed nine items of the EORTC item bank regarding financial difficulties, seven work-related questions, the Hospital Anxiety and Depression Scale, Cancer Worry Scale and EORTC QLQ-C30.ResultsIn total, 328 GIST patients participated (response rate 63.0%), of which 110 (33.8%) were on TKI treatment. Patients currently treated with TKIs reported significantly more financial difficulties compared to patients not on TKIs (17.3% vs 8.7%, p = 0.03). The odds of experiencing financial difficulties was 18.9 (95% CI 1.7–214.7, p = 0.02) times higher in patients who were less able to work due to their GIST diagnosis. Patients who experienced financial difficulties had significantly lower global quality of life and functioning, and more frequently reported psychological symptoms as compared to patients who did not report financial difficulties.ConclusionEven in a country where the costs of TKIs and follow-up care are covered by health insurance, financial difficulties can be present in GIST patients, especially in patients on TKI treatment, and may negatively influence the quality of life.

Imaging of pediatric gastrointestinal tumors: A tertiary center experience over 19 years

PurposeGastrointestinal tract (GIT) tumors in children are rare and there is a scarcity of data on their imaging features. The purpose of this study was to determine thefrequency of various GIT tumor types in children and to identify key imaging characteristics. MethodsThis retrospective, single-center study was approved by the local ethics committee. Children with histologically proven GIT tumours (malignantand benign) who had imaging available on the institutional PACS between May 1, 2000 and Dec 31, 2019 were included. Demographic data and available imaging was reviewed by two blinded radiologists. ResultsIn total, 90 children (45 male, mean age 9.3 ± 4.3 years) with GIT tumours were included. The final diagnoses included polyps (n = 28), lymphomas/PTLD (n = 27), neuroendocrine tumours (n = 16), adenocarcinoma (n = 6), adenoma (n = 5), gastrointestinal stromal tumor (GIST) (n = 3), inflammatory myofibroblastic tumours (n = 2) and lastly leiomyoblastoma, leiomyoma and lipoma (1 each). All GIT segments were affected, but overall the small and large bowel had most lesions. Eighty-one percent children had a single lesion while remaining 19 % had multiple lesions. The neoplastic process manifested as intra-luminal lesion (58 %) or wall thickening (42 %) on imaging. Multiple cystic areas and vascular pedicle for polyps; and hypoechogenecity of the mass or wall thickening and aneurysmal dilatation for lymphomas, were the characteristic imaging features. None of the neuroendocrine tumours affecting appendix were seen on pre-resection imaging. ConclusionsVariety of benign and malignant tumors are seen throughout the childhood. Polyps, lymphomas and appendiceal neuroendocrine tumors are common lesions. Characteristic imaging features of juvenile polyps and lymphomas on ultrasound may help narrowing the differentials, and guide further work up.

Expression of TGF-β1 in Gastrointestinal Stromal Tumor (GIST) and the Occurrence of Frequent Desmoplasia.

Gastrointestinal stromal tumors (GISTs) are mesenchymal neoplasms with variable behavior characterized by differentiation toward the interstitial cells of Cajal occurring anywhere in the gastrointestinal stromal tract. Frequently, GISTs have fibrous stroma within tumor cell proliferation areas, which is unlike other types of malignant tumors. If this desmoplasia is active, there is a possibility that some sort of transmitter exists between GIST cells and cells related to fibrosis in the tumor cell proliferation areas. Transforming growth factor (TGF)-β isoforms, particularly TGF-β1, are critical for fibrosis pathogenesis. TGF-β1 regulation of myofibroblasts and fibroblasts during fibrosis is well described. The induced fibroblast activation resulting in myofibroblast differentiation has been reported as an important source of collagen, glycoproteins, proteoglycans, and matrix metallopeptidases in wound healing and fibrosis. However, there are a few reports on the relationship between TGF-β1 and GISTs. This study aims to clarify TGF-β1 expression in 30 gastric GISTs using immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR). For comparison, we also enrolled 30 samples of gastric tubular adenocarcinoma (GTAC). We confirmed TGF-β1 expression (H-score ≥50 points) in 57% of GIST and 13% of GTAC samples, a significant difference between the 2 tumor types ( P =0.001). We examined the TGF-β1 mRNA expression of 3 representative GIST samples, each having their respective immunostained areas detected by RT-PCR. Finding TGF-β1 expression may indicate that this cytokine plays a part in the formation of desmoplasia within GIST cell proliferative areas.

Gastrointestinal stromal tumors : Where do we stand?

For more than 20 years gastrointestinal stromal tumors (GIST) have been aparadigm for atargeted treatment with tyrosine kinase inhibitors. Afundamental prerequisite for aneoadjuvant or adjuvant treatment of localized GIST or an additive treatment of metastatic GIST is the molecular typing of tumors, ideally at the initial diagnosis. In addition, the possibility of ahereditary or syndromic predisposition must be considered because this results in consequences for the treatment and adifferent follow-up strategy.

Abstract CT290: Trial in progress: Evaluation of the safety, tolerability, whole-body distribution, radiation dosimetry and antitumor activity of 177Lu-NeoB in patients with advanced solid tumors expressing gastrin-releasing peptide receptor (GRPR)

Abstract Introduction: Many common cancers such as breast, lung, and prostate, plus several less common malignancies such as gastrointestinal stromal tumors (GIST) and glioblastoma (GBM) express or are associated with the Gastrin-Releasing Peptide Receptor (GRPR). Therefore, GRPR could be utilized for the development of innovative approaches to tumor imaging and therapeutic interventions. NeoB is a new generation bombesin analog, which binds to GRPR with high affinity/specificity. The structure of NeoB permits radiolabeling with gallium-68 [68Ga] (for imaging) or lutetium-177 [177Lu] (for therapy), making it suitable for theranostics. Pre-clinical and early phase clinical data confirmed the utility of [68Ga]-NeoB for identification of GRPR-expressing tumors and demonstrated the in vitro and in vivo antitumor activity of [177Lu]-NeoB. In the Phase IIa part of this first-in-human study of [177Lu]-NeoB (NeoRay; NCT03872778), we aim to characterize the safety, tolerability, whole-body distribution, radiation dosimetry and antitumor activity of [177Lu]-NeoB in patients with selected advanced solid tumors known to express GRPR. Methods: The Phase IIa part of this Phase I/IIa multi-center, open-label study will enroll approximately 50 adult patients (age ≥18 years old) with advanced/metastatic cancers and for whom no standard therapy is available, tolerated or appropriate. Patients will be enrolled across 4 cohorts: HR-positive, HER2-negative breast cancer (Cohort A), prostate cancer (Cohort B), GIST (Cohort C) or any solid tumor overexpressing GRPR including recurrent GBM, and who have moderate renal impairment (CrCl ≥30 mL/min - <60 mL/min; Cohort D). Eligible patients must have at least one measurable lesion with confirmed uptake of [68Ga]-NeoB and have an ECOG performance status of ≤1. Patients will be treated with [177Lu]-NeoB at the recommended Phase II dose (9.25 GBq [250 mCi]) for a minimum of 2 treatment cycles, each lasting 6 weeks. The primary endpoints are assessment of the disease control rate with [177Lu]-NeoB in cohorts A, B and C, and evaluation of the pharmacokinetics (PK), biodistribution and radiation dosimetry in patients with impaired renal function (Cohort D). Secondary endpoints include assessment of the antitumor activity, PK, distribution, radiation dosimetry, and impact on the quality of life of patients in the [177Lu]-NeoB cohorts (A, B and C) as well as the safety and tolerability of both [177Lu]-NeoB and [68Ga]-NeoB across all cohorts. Citation Format: Erik Mittra, Andrei Iagaru, Astrid Van der Veldt, Luigi Aloj, Jeffrey Wong, Loic Djaileb, Dhrubajyoti Pathak, Yongmin Liu, Lilja Solnes. Trial in progress: Evaluation of the safety, tolerability, whole-body distribution, radiation dosimetry and antitumor activity of 177Lu-NeoB in patients with advanced solid tumors expressing gastrin-releasing peptide receptor (GRPR) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT290.

Abstract CT089: A phase 1 multi-center, open label, dose escalation study to evaluate the safety, pharmacokinetics (PK) and anti-tumor activity of T-1301, a novel small molecular multi-target kinase inhibitor, in patients with advanced solid tumors

Abstract Background: T-1301 is a novel small molecule multi-target kinase inhibitor, it also exhibited potent inhibitory activity against both wild type and mutant forms of various kinases, i.e., ABL1, FLT3, c-KIT, PDFGRA, RET, and TRKA. In in vitro studies, T-1301 effectively inhibited growth of acute myeloid leukemia (AML) as well as gastrointestinal stromal tumor (GIST) cells carrying mutations that are resistant to KIT-targeting tyrosine kinase inhibitors (TKIs) in clinical use. In animal studies, tumor regressions were observed in AML and GIST xenograft models, while growth inhibition were observed in various other types of solid tumor models. Method: This is an open label, multi-centered Phase 1 dose escalating study (NCT05156203). The primary objectives are to establish the maximal tolerated dose (MTD) and recommended Phase 2 dose (RP2D), and to assess the safety and tolerability of T-1301. The secondary objectives are to evaluate the pharmacokinetics (PK) and therapeutic response after receiving treatment. Eligible Patient should have histologically and cytologically confirmed advanced solid tumors (including lymphoma) with measurable or evaluable target lesion(s) per RICEST v1.1 and refractory to or without standard treatments, ECOG performance status 0-1, and adequate organ function. The dose escalation begins with accelerated titration and switch to the Bayesian Optimal Interval (BOIN) design when either one of the following events is observed in Cycle 1: the first instance of DLT, or any Grade 2 or higher drug-related adverse event (AE) in any patient. Then, at least 2 additional subjects are treated at the current dose level and the dose escalation will follow the Bayesian Optimal Interval (BOIN) design with cohorts of size 3-6.T-1301 is orally administered daily in a 28-day cycle (a 21-day consecutive dosing followed by a 7-day rest). The dosing schedule is once daily (QD) at the initial dose level and could be QD or twice daily starting with the second dose level according to the safety review committee (SRC) decision after reviewing the safety and PK data from each dose level. AEs are assessed according to CTCAE v5.0 and occurrence of dose limiting toxicity (DLT) is determined during the first cycle of treatment. The safety findings are reviewed by the SRC, which will determine the MTD and RP2D. Tumor response evaluation is performed after 2 cycles of treatment and assessed according to RECIST v1.1 criteria. For those who benefit from the study medication after 2 treatment cycles, intra-subject dose escalation for multiple times is allowed in extension study period. Patient recruitment began in December 2021 and is ongoing in Taiwan. Citation Format: Jen-Shi Chen, Ming-Huang Chen, Yi-Chang Liu, Wen-Chi Chou, Nai-Jung Chiang, Hui-Ching Wang, Ta-Sen Yeh, Shih-Feng Cho, Cheng-Hsu Wang, I-Fang Lee, Li-Tzong Chen. A phase 1 multi-center, open label, dose escalation study to evaluate the safety, pharmacokinetics (PK) and anti-tumor activity of T-1301, a novel small molecular multi-target kinase inhibitor, in patients with advanced solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT089.

Treatment Access for Gastrointestinal Stromal Tumor in Predominantly Low- and Middle-Income Countries

Gastrointestinal stromal tumor (GIST) is a rare cancer treated with the tyrosine kinase inhibitors imatinib mesylate or sunitinib malate. In general, in low- and middle-income countries (LMICs), access to these treatments is limited. To describe the demographic characteristics, treatment duration, and survival of patients with GIST in LMICs treated with imatinib and sunitinib through The Max Foundation programs. This retrospective database cohort analysis included patients in 2 access programs administered by The Max Foundation: the Glivec International Patient Assistance Program (GIPAP), from January 1, 2001, to December 31, 2016, and the Max Access Solutions (MAS) program, January 1, 2017, to October 12, 2020. Sixty-six countries in which The Max Foundation facilitates access to imatinib and sunitinib were included. Participants consisted of patients with approved indications for imatinib, including adjuvant therapy in high-risk GIST by pathologic evaluation of resected tumor or biopsy-proven unresectable or metastatic GIST. All patients were reported to have tumors positive for CD117(c-kit) by treating physicians. A total of 9866 patients received treatment for metastatic and/or unresectable disease; 2100 received adjuvant imatinib; 49 received imatinib from another source and were only included in the sunitinib analysis; and 53 received both imatinib and sunitinib through The Max Foundation programs. Data were analyzed from October 13, 2020, to January 30, 2024. Demographic and clinical information was reported by treating physicians. Kaplan-Meier analysis was used to estimate time to treatment discontinuation (TTD) and overall survival (OS). An imputation-based informed censoring model estimated events for patients lost to follow-up after treatment with adjuvant imatinib. Patients who were lost to follow-up with metastatic or unresectable disease were presumed deceased. A total of 12 015 unique patients were included in the analysis (6890 male [57.6%]; median age, 54 [range, 0-100] years). Of these, 2100 patients were treated with imatinib in the adjuvant setting (median age, 54 [range 8-88] years) and 9866 were treated with imatinib for metastatic or unresectable disease (median age, 55 [range, 0-100] years). Male patients comprised 5867 of 9866 patients (59.5%) with metastatic or unresectable disease and 1023 of 2100 patients (48.7%) receiving adjuvant therapy. The median OS with imatinib for unresectable or metastatic disease was 5.8 (95% CI, 5.6-6.1) years, and the median TTD was 4.2 (95% CI, 4.1-4.4) years. The median OS with sunitinib for patients with metastatic or unresectable GIST was 2.0 (95% CI, 1.5-2.5) years; the median TTD was 1.5 (95% CI, 1.0-2.1) years. The 10-year OS rate in the adjuvant setting was 73.8% (95% CI, 67.2%-81.1%). In this cohort study of patients with GIST who were predominantly from LMICs and received orally administered therapy through the GIPAP or MAS programs, outcomes were similar to those observed in high-resource countries. These findings underscore the feasibility and relevance of administering oral anticancer therapy to a molecularly defined population in LMICs, addressing a critical gap in cancer care.

Jejunojejunal intussusception induced by a gastrointestinal stromal tumor: a case report and literature review.

Intussusception is defined as the invagination of a proximal segment of the bowel into the adjoining or distal segment. In most adults with intussusception, there is a demonstrable lead point with a definite pathologic abnormality. The clinical features of intussusception include chronic intermittent abdominal pain, nausea and vomiting, constipation, and a palpable abdominal mass. The present case report describes a 62-year-old woman with a 2-week history of abdominal pain and 9-day history of vomiting. Clinical, imaging, and histologic evaluations revealed a jejunojejunal intussusception with a gastrointestinal stromal tumor as the lead point. A gastrointestinal stromal tumor should be considered as a possible lead point in adult patients with intussusception. The implication of reducing the intussusception prior to tumor resection requires further evaluation in view of the risk of venous embolism, including direct spread of malignant cells, in cases involving a large polypoid mass with a necrotic surface that extends to the serosa as shown by intraoperative examination. Accordingly, the rationale for adjuvant therapy with imatinib also requires further evaluation.

Contribution of genetic polymorphism in ABCB1 to individual variations of imatinib plasma levels in patients with gastrointestinal stromal tumor.

Imatinib mesylate (IM) is a first-line treatment option for the majority of patients diagnosed with gastrointestinal stromal tumors (GISTs). Although the clinical benefit is high, interindividual response is variable. This study thus aimed to assess how genetic polymorphisms can affect the blood levels of IM and treatment outcomes in patients with GIST. A total of 31 single-nucleotide polymorphisms (SNPs) in selected cytochrome P450 (P450), ATP-binding cassette transporter (ABC), solute carrier family (SLC), interleukin-4 receptor (IL4R), and vascular endothelial growth factor (VEGF) genes were genotyped using an SNP mass array platform. A total of 192 consecutive patients with GIST who received 400 mg of IM daily were enrolled into the study, with 1,485 blood samples being analyzed. According to genotypes, IM trough concentrations were tested and compared. Progression-free survival (PFS) and overall survival (OS) were also assessed. With a mean follow-up of 75.99 months, trough concentrations of imatinib were examined at average time points of 7.73 for each patient. Polymorphism in ABCB1 rs1045642 was found to be associated with steady-state IM trough plasma levels (P=0.008). Patients with the C genotype (CT + CC) of rs1045642 exhibited higher IM trough concentrations (1,271.09±306.69 ng/mL) compared to those with the TT genotype (1,106.60±206.05 ng/mL). No statistically significant differences in IM plasma concentration were observed for the other SNPs tested. None of the tested SNPs displayed a significant association with patients' survival in this study. This is the largest cohort study evaluating the associations of SNP and imatinib blood trough levels. The ABCB1 rs1045642 genetic polymorphism may exert an effect on the pharmacokinetics of imatinib. The presence of the C allele in ABCB1 rs1045642 is predictive of a higher plasma concentration of IM.

Current Perspectives on Small Bowel Tumors: Overview of Prevalence, Clinical Manifestations, and Treatment Approaches

Small bowel tumors (SBTs) constitute a rare yet increasingly recognized group of gastrointestinal neoplasms, accounting for less than 5% of all gastrointestinal cancers. Despite their infrequency, the incidence of SBTs has exhibited a notable upward trend, underscoring the importance of understanding these diverse and complex tumors. This review consolidates current knowledge on SBTs, encompassing epidemiology, risk factors, clinical manifestations, diagnostic advancements, and treatment modalities. Data from various sources are analyzed to present a comprehensive overview of the evolving landscape of SBTs. Our findings indicate that adenocarcinomas, carcinoid tumors, lymphomas, and gastrointestinal stromal tumors (GISTs) are the common SBTs. While adenocarcinoma and neuroendocrine tumors are the common types of SBTs in the West, GIST and lymphoma are more common in Asia. Common risk factors include genetic syndromes and inflammatory bowel diseases. There is variability in clinical presentations depending on the type of tumors. Although diagnostic challenges persist, advancements in imaging and endoscopic techniques have improved detection rates. Treatment strategies are evolving; surgical resection remains the mainstay for localized disease, augmented by systemic therapies and targeted agents for advanced stages. This review emphasizes the importance of early detection and individualized treatment approaches in improving outcomes for SBT patients. It addresses the need for ongoing research and innovation in managing these tumors.

The long-term efficacy of imatinib with hepatic resection or other local treatment for gastrointestinal stromal tumours liver metastases: a retrospective cohort study.

The liver is the most common site of metastasis from gastrointestinal stromal tumors (GISTs). The authors aimed to evaluate imatinib (IM) combined with hepatic resection (HR) or other local treatments such as radiofrequency ablation (RFA) and transarterial chemoembolization (TACE), compared to IM monotherapy in long-term survival benefits in patients suffering from GIST liver metastases. Our research encompassed 238 patients diagnosed with liver metastases of GISTs from January 2002 to April 2022 at the First Affiliated Hospital of Sun Yat-Sen University. The oncological outcomes of concern included overall survival (OS), progression-free survival (PFS), and liver-specific PFS. Of all 238 patients, 126 were treated with IM alone (IM group), 81 with IM combined with HR (IM+HR group), and 31 with IM combined with RFA/TACE (IM+RFA/TACE group). The median follow-up time was 44.83 months. The median OS in the IM group was 132.60 months and was not reached in either the IM+HR group or the IM+RFA/TACE group. The 10-year OS rate in the IM+HR group was significantly superior to the IM group and the IM+RFA/TACE group (91.9% vs. 61.1% vs. 55.2%, respectively, P =0.015), and the liver-specific PFS ( P =0.642) and PFS ( P =0.369) in the three groups showed a beneficial trend in the combined treatment group. Multivariate analyses showed that age less than or equal to 60 years (HR 0.280, P< 0.001) and IM+HR (HR 0.361, P =0.047) were independently associated with better OS. Achieving no evidence of disease through surgical intervention was independently correlated with enhanced OS (HR 0.099, P =0.034), liver-specific PFS (HR 0.388, P =0.014), and PFS (HR 0.402, P =0.004). In patients with GIST liver metastases, IM combined with HR might improve OS in selected patients compared with IM alone and IM combined with RFA/TACE. Achieving no evidence of disease status with surgical treatment of patients results in significant prolonging of OS, liver-specific PFS, and PFS.

Primary small-bowel gastrointestinal stromal tumor presenting with severe anemia: A report of two cases

Gastrointestinal stromal tumors are rare mesenchymal neoplasms that commonly occur in the stomach and small intestine and can occur anywhere from the esophagus to the anus. We are reporting two cases with identical presentations of severe anemia and abdominal discomfort, which revealed the diagnosis of primary small-bowel gastrointestinal stromal tumour (GIST), on computed tomography (CT), as standard endoscopy investigations failed to reveal the cause for the anemia. Both patients underwent surgical resection for the lesions and histopathological examination confirmed the diagnosis of GIST. After surgical management, hemoglobin levels of both patients improved, and were discharged with uneventful postoperative course. These case reports stress the importance of contrast-enhanced computed tomography (CT) scans, for investigating anemia, along with the standard endoscopy tests.

Solid pseudopapillary neoplasm of the pancreas during pregnancy presenting as gastrointestinal stromal tumor: A case report and review of literature

Solid pseudopapillary neoplasm (SPN) is a rare tumor that can complicate pregnancy. More than its rarity, SPNs are unique neoplasms because of their obscure histogenesis, cytology, immunohistochemical profile, and imaging characteristics. This report describes the case of a 32-year-old gravida 2 para 1 (1001) seen at 24 weeks with an intra-abdominal mass. The patient presented with a long-standing history of abdominal mass with the working impression of gastrointestinal stromal tumor. We employed a multidisciplinary approach to closely monitor tumor growth, ensure maternal and fetal well-being, avert complications, and avoid unnecessary clinical interventions. Histopathological evaluation and immunohistochemistry studies of representative specimens taken at the time of delivery revealed the diagnosis of SPN of the pancreas. Based on a review of local search engine databases, this is the first documented case of SPN complicating pregnancy in the Philippines.

Evaluation of Gastro Intestinal Stromal Tumor in a Tertiary Care Center

INTRODUCTION: Gastrointestinal stromal tumour (GIST) is an uncommon entity in clinical practice. It accounts for only &lt;1% of all Gastrointestinal (GI) malignancies. Stomach is the commonest site for this tumour. Other sites of GI tract are also affected with GIST. AIMS AND OBJECTIVES: This study aimed evaluate the prognostic factors, and recurrence patterns among the patients of eastern India. MATERIAL AND METHODS: This was a retrospective observational study which was conducted at the Department of Pathology in a tertiary care centre of eastern India. The specimens sent for HPE during the period June, 2018 to June, 2023 were included in the study. A total number of 2897 GI specimens sent to the Department for histopathological examinations were selected for the study. Out of which 77 specimens were diagnosed as GIST. The information of the vital parameters of the patient, type of tumour and type of treatments offered were collected for evaluation. The histological examinations relied on morphological features on Hematoxylin &amp; Eosin stain and confirmation with immunohistochemistry markers CD34 and CD117 and S100. Patients with operable GIST underwent Surgery followed by adjuvant therapy. Patients with inoperable/ borderline operable disease underwent neoadjuvant Tab. Imatinib 400 mg/day followed by reassessment for surgery. RESULTS: The mean (±S.D.) age of the patients was 54.58±11.24 years with range of 28 -74 years and the median age was 54 years. 66.2% of the patients were with age&lt; 60 years (p&lt;0.001). Proportion of females (54.5%) was higher than males (45.5%) but it was not significant. Stomach (54.5%) was the most common site of tumour which was significantly higher than small intestine (27.3%) and large intestine (18.2%) (p&lt;0.0001). At presentation non-metastatic cases (62.3%) were significantly higher than metastatic (35.1%) and locally recurrent cases (2.6%) (p&lt;0.0001). In most of the cases the mitotic rate was between 5 – 10 /50 HPF (53.2%) which was significantly higher than mitotic rate &lt;5/50 HPF (32.5%) and &gt;10/50 (14.3%) (p=0.0042). Spindle cell type tumour (71.4%) was significantly higher than mixed (Spindle and Epithelioid) (20.8%) and Epithelioid type tumour (7.8%) (p&lt;0.0001). CONCLUSION: GIST is a rare tumor of the GI tract. It usually occurs in the stomach. The treatment of choice is surgery followed by adjuvant therapy.

Prognostic impact of positive microscopic margins (R1 resection) in patients with GIST (gastrointestinal stromal tumours): Results of a multicenter European study

BackgroundAlthough several prognostic factors in GIST have been well studied such as tumour size, mitotic rate, or localization, the influence of microscopic margins or R1 resection remains controversial. The aim of this study was to evaluate the influence of R1 resection on the prognosis of GIST in a large multicentre retrospective series of patients. MethodsFrom 2001 to 2013, 1413 patients who underwent surgery for any site of GIST were identified from 61 European centers. 1098 patients were included, excluding synchronous metastases, concurrent malignancies, R2 resection or GIST recurrence. Tumour rupture (TR) was reclassified according to the Oslo sarcoma classification. Cox proportional hazards ratio and Kaplan-Meier survival estimates were used to analyse 5-year recurrence-free survival (RFS). ResultsOf 1098 patients, 38 (3%) underwent R1 resection with a risk of TR of 11%. The 5-year RFS was 89.6% with a median follow-up of 81 months [range: 31.2–152 months]. On univariate analysis, lower RFS was significantly associated with R1 resection [HR = 2.13; p = 0.04], high risk score according to the modified NIH classification, administration of adjuvant therapy [HR = 2.24; p < 0.001] and intraoperative complications [HR = 2.82; p < 0.001]. Only intraoperative complications [HR = 1.79; p = 0.02] and high risk according to the modified NIH classification including the updated definition of TR [HR = 3.43; p = 0.04] remained significant on multivariate analysis. ConclusionThis study shows that positive microscopic margins are not an independent predictive factor for RFS in GIST when taking into account the up-dated classification of TR. R1 resection may be considered a reasonable alternative to avoid major functional sequelae and should not lead to reoperation.

GASTROINTESTINAL STROMAL TUMORS. COURSE PREDICTION AND DIAGNOSTIC ALGORITHMS

The purpose of the review is to compare modern algorithms for predicting the course of GIST.Material and methods. An information search was conducted using the PubMed, OVID, EMBASE, SRC BOLD databases using keywords that corresponded to the MESH terms «gastro-i ntestinal stromal tumors» AND «prognosis» AND «diagnosis». The search depth is 10 years. From the total array of 66 publications, 20, most relevant to the search subject, were selected. Information analysis was carried out in accordance with the PRISMA criteria.The results. A comparison of various medical imaging methods and models for predicting clinical outcomes in GIST was carried out. The main prognostic criteria are the size of the tumor, its localization and mitotic index. Criteria for assessing the response to treatment during MRI and PET were revised. The diff erences, advantages, and limitations of various prognosticators are discussed Conclusions. Gastrointestinal stromal tumors are a rare pathology, which, however, often has a progressive course. Existing models for predicting the course of GIST do not take into account genetic variants. The use of a multidisciplinary approach has signifi cant prospects in the selection of SPSHKT therapy.

ANALYSIS OF MORPHOLOGICAL GASTRIC CANCER TYPES

Malignant neoplasms occupy the leading places in the structure of morbidity and mortality of the world's population. Stomach cancer is one of the five most common cancer types in Russia in terms of morbidity and is among the top three in terms of mortality from malignant neoplasms. The aim of the study is to study the morphological gastric cancer types depending on the stage, localization of the tumor process in the stomach and the age of the patient. Materials and methods. A retrospective analysis of data on 412 stomach cancer patients for 2022–2023, examined on the basis of the AI "Republican Clinical Oncology Dispensary" under the Health Ministry of Chuvashia, among whom there were 256 (62.1%) men and 156 (37.9%) women, was carried out. The average age of the patients was 65.6±12 years. All cases have morphological verification. Research results. The most frequently diagnosed morphological types of gastric cancer were identified: adenocarcinoma not otherwise specified (57.3%), colloid cancer (17.2%), less often – gastrointestinal stromal tumor (6.7%) squamous cell non-keratinizing carcinoma (4.1%). The remaining tumor types in gastric cancer were verified less frequently (0.2–3.0%). It was found that the most common morphological types of gastric cancer were detected in most cases in the elderly (over 60 years old) and males. Depending on the tumor localization in the stomach departments, it was verified: if the body of the stomach is affected, almost all types of stomach cancer are observed (the same with affection to the antrum), such types as tubular, micropapillary, neuroendocrine, scyrrhous and mixed were not found in the cardiac department of the stomach. In subtotal and total affection of all stomach parts, the morphological types of gastric cancer corresponded in most cases to not otherwise specified adenocarcinoma and colloid carcinoma. Such morphological type of gastric cancer as not otherwise specified adenocarcinoma which made up the bulk of all types of malignant gastric cancers, was mainly (in 52.1%) detected at stages III and IV of the disease and only in 16.9% of patients – at the early I stage of the disease. Other morphological types of gastric cancer identified in the late stages of the tumor process included colloid carcinoma, non-keratinizing squamous cell carcinoma and carcinoma simplex. Conclusions. The analysis of morphological gastric cancer types the predominance of adenocarcinomas and colloid cancer, identified more often in the late stages of the tumor process. The predominant localization of various morphological types of gastric cancer with body damage was established. The most common morphological types of gastric cancer are found in the elderly, more often in men.

Laparoscopic Resection of Gastric GIST Tumor

After a patient is found to have a gastrointestinal stromal tumor (GIST), David Rattner, MD performs a laparoscopic resection, carefully avoiding the nerves of Latarjet. He then confirms the success of the procedure with an upper GI endoscopy.

Genomic and clinical characterization of a familial GIST kindred intolerant to imatinib

Familial gastrointestinal stromal tumors (GIST) are rare. We present a kindred with multiple family members affected with multifocal GIST who underwent whole genome sequencing of the germline and tumor. Affected individuals with GIST harbored a germline variant found within exon 13 of the KIT gene (c.1965T>G; p.Asn655Lys, p.N655K) and a variant in the MSR1 gene (c.877 C > T; p.Arg293*, pR293X). Multifocal GISTs in the proband and her mother were treated with preoperative imatinib, which resulted in severe intolerance. The clinical features of multifocal GIST, cutaneous mastocytosis, allergies, and gut motility disorders seen in the affected individuals may represent manifestations of the multifunctional roles of KIT in interstitial cells of Cajal or mast cells and/or may be suggestive of additional molecular pathways which can contribute to tumorigenesis.

A canine mastocytoma with oncogenic c-kit activation by intra-exonic alternative splicing

We report a subcutaneous mastocytoma in a mid-aged Italian greyhound dog with a small 41 bp genomic deletion of the c-kit gene leading to skipping of the authentic 3′-splice junction of intron 10. The shift to an alternative splice junction in exon 11 leads to a mis-spliced in-frame mRNA transcript with a 27 bp deletion of exon 11 coding for 9 amino acids in the juxtamembrane negative regulatory domain of c-kit tyrosine kinase. In the tumor, c-kit was activated as revealed by more pronounced c-kit-regulated signaling by the PI3K/Akt and G-coupled receptor pathways. The same 9 amino acids deletion was reported in several human gastrointestinal stromal tumors (GIST) pointing to a remarkable similarity of c-kit activation by small deletions and aberrant splicing in humans and dogs, independent of exact sequence context, tumor type and location. Interestingly, the alternative splice junction in exon 11 has been conserved in Primates but less in other Orders with increased body temperature such as ruminants. We hypothesize that elevated body temperature has acted as evolutionary pressure to eliminate the alternative splice site at this hotspot. At a molecular level, hyperthermia may increase the frequency of small deletions in the c-kit gene by facilitating base slipping or hindering repair. An RT-qPCR assay was developed to detect c-kit alternative splicing in tumors and cell lines exposed to hyperthermia. The molecular mechanisms of tumorigenesis are discussed.