Primary GIST Research Articles

S2959 Primary Rectal GIST: A Case Series and Literature Review

S2959 Primary Rectal GIST: A Case Series and Literature Review

Lesser Curvature and Omentum-Dependent Spindle Cell Tumor: Literature Review Regarding a Case

GIST tumors are a group of rare neoplasms, having a reported incidence of 6/10 million people annually. 70-80% of the GIST are benign, however there are prognostic factors which can help us to predict its behavior. The stomach and the small intestine are the most frequent sites of location of these tumors. Diagnosis is not only based on clinical suspicion, we must also use imaging tools and pathology to confirm it. Surgery is the treatment that offers a permanent cure for localized primary GIST.

Primary Pancreatic GIST - A-Single Centre Case Series and Systematic Review of Literature.

GISTs arising from organs outside GI tract are defined as extragastrointestinal GISTs (EGIST). The majority of EGISTs arise from small intestinal mesentry, mesocolon, omentum, retroperitoneum, abdominal wall, liver and pancreas with pancreas comprising less than 5% of it. Due to limited data, it is unknown if the results of GIST can be generalised for EGISTs. We thereby present the largest single-centre case series of primary pancreatic GIST so far with review of existing literature. A total of 9 patients of primary pancreatic GIST were treated at our institute from September 2016 to February 2023. After literature search for all studies published before February 2023, 51 articles including 57 patients were identified. Their clinicopathological data and survival analysis were assessed. The median age of patients treated at our centre was 53years with a female predominance. The most common epicentre was pancreatic head with abdominal pain as the most common presenting symptom. All 57 patients documented in literature belonged to a similar age group with similar gender predilection. The factors impacting DFS were histologic type, mitotic index, NIH risk category and adjuvant therapy. The median DFS was 74months with a 5-year DFS being 71.9%, while the 5-year OS was 90.4%. Pancreatic GIST is a rare entity. Due to limited evidence and evolving literature, results cannot be generalised to a larger population. Larger case series with longer follow-up data are required to further understand the disease biology and long-term outcomes of pancreatic GIST.

Correlation of Diffusion weighted MR Imaging and ADC values of hepatic metastasis of Gastrointestinal Stromal and Gastroenteropancreatic Neuroendocrine Tumors.

DWI and ADC-mapping was performed to analyze hepatic metastasis of GIST, GEP-NET. The objective of this study is to present hepatic metastasis of GIST and GEP-NET with Diffusion weighted MR imaging(DWI) and the Apparent diffusion coefficients (ADC) values of masses. 18 GIST patients and 8 GEP-NET patients were examined retrospectively. 11 males and 6 females were present in GIST group, 7 males to 5 females were involved in GEP-NET group. 18 primary GIST and 10 hepatic metastasis of GIST, 8 original GEP-NET and 19 hepatic metastasis of GEP-NET; total 55 GIST and GEP-NET masses were analysed by ADC mapping. MR images were acquired by 1,5 T MR units (32 mT/min gradient strength- Achieva; Philips Healthcare, Best, Netherlands and 32 channel GE Signa GE-Wisconsin-USA); by using a 4-8 channel standard phased-array torso XL coil, all images were evaluated by an Abdominal MRI experienced radiologist. DWI was performed in the transverse plane by using spin-echo-planar imaging sequence. No statistical differences were observed between GIST and GEP-NET patients according to age and gender variations. No significant statistical differences were observed according to the diameters and ADC values of GIST and GEP-NET patients. A significant statistical difference was observed between GIST and GEP-NET groups in terms of size of liver metastasis which was significantly higher in GIST patients. All three groups (GIST_Hep. MET, GEP-NET_Liver_Met and normal) were statistically differed according to ADC values. With the ROC curve analysis: Hepatic metastasis of GIST(n=10) and normal liver (n:47) had cut-off value for ADC: 0.925 under AUC: 0.939 with regard to ADC values and regarded 89.4 % Sensitivity, 100% Specificity, 100% PPV and 66.7% PPV. ROC curve of GEP NET_ Hepatic metastasis (n=19) group and normal liver (n:47) group presented cut-off value for ADC: 0.860 under AUC: 0.967 correlated to ADC values with 93.6 % sensitivity, 89.5% specificity, 95.7% PPV and 85% PPV. High cellular tumors resulted from liver metastasis of GIST and GEP-NET's, and a positive correlation was observed between ADC values and cellularity/differentiation ratios of metastatic masses.

Mucosal Ulceration in Gastrointestinal Stromal Tumor is an Independent Predictor of Progression-Free Survival

IntroductionGastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal (GI) tract. Known prognostic features of GISTs include tumor mitotic rate, size, and location, yet one common feature of primary GISTs for which prognostic significance is unknown, is mucosal ulceration. This study aims to investigate the significance of mucosal ulceration in GISTs. Materials and methodsA retrospective study was conducted of 513 patients at a tertiary referral center with a suspected or documented diagnosis of primary GIST between the years of 2000 and 2020. Ulceration was confirmed by definitive documentation in the endoscopic or histopathologic report. The significance of ulceration in GIST was compared to other prognostic factors. ResultsOf the 513 patients reviewed, 310 primary GIST patients with known ulceration and disease status were identified. Of those, 27.4% (n = 85) demonstrated mucosal ulceration. Mucosal ulceration in GISTs is associated with GI bleeding, mitotic rate, tumor size, and exon 11 mutations. After a median follow-up of 35.4 (interquartile range = 17.1-62.2) mo, patients with ulcerated GISTs experienced higher rates of tumor progression (40.0% versus 14.2%, P < 0.0001). In multivariate analysis, ulceration of GISTs was highly associated with disease progression (P < 0.0001) and progression-free survival (hazard ratio = 2.4 [1.2-4.7], P = 0.01). ConclusionsMucosal ulceration in GISTs is associated with GI bleeding, mitotic rate, tumor size, and exon 11 mutations. Overall, ulceration in GISTs is associated with elevated risk of tumor progression and is an independent prognostic factor. In multivariate analysis, ulceration in GIST remains an independent risk factor for disease progression.

EP-262 Neoadjuvant imatinib for Resectable Gastrointestinal Stromal Tumors. A State-of-the-art

Abstract Aims Surgical removal remains the cornerstone of primary GIST treatment and complete surgical resection offers prognostic value toward risk of relapse. However, primary tumors, particularly of the stomach, are of advanced size when detected, and multivisceral resection seems to be the treatment of choice. Existing results of recent clinical trials have established the feasibility of neoadjuvant imatinib therapy mainly in unresectable GISTs. Yet, proof of the survival effectiveness of neoadjuvant imatinib therapy in borderline resectable tumors has not been sufficiently demonstrated. Methods A review of the literature was performed to identify the current evidence for preoperative treatment of large GISTs with Imatinib regarding R0 resection and oncological outcome. Results Data supporting benefit of neoadjuvant imatinib are available from several case reports and small retrospective series, most of which include a mix of patients with borderline resectable and unresectable primary disease. In addition, a single-phase II United States Intergroup trial and an Asian phase II trial of neoadjuvant therapy in large stomach tumors, concluded that Neoadjuvant imatinib therapy is preferred for marginally resectable tumors. Progressive disease after neoadjuvant treatment was a rare event, and partial response was achieved in 40–80% of all patients. Conclusion Neoadjuvant therapy with imatinib is safe and recommended for patients with resectable, locally advanced GIST. It may also enable less invasive and organ-sparing surgery, increase the complete resection rate, and avoid the surgical rupture by decreasing the tumor size. Clinical questions still remain about the most appropriate period of pre- and post-operative imatinib administration in the neoadjuvant protocol.

The long-term analysis of prognostic role of mutational status in primary resectable gastrointestinal stromal tumors (GIST).

e23517 Background: Radical surgery is the primary treatment for GIST, but up to 50% of patients relapse, mainly in form of hepatic and peritoneal metastases. GISTs are a group of tumors with various pathological and molecular features as well as different clinical courses. The aim of the study was the long-term analysis of prognostic role of mutational status in primary GIST after radical resection. Methods: The material consisted of a group of 304 patients with primary GIST diagnosed till 04/2012, with known mutational status and treated surgically with curative intend without adjuvant imatinib. Data were collected prospectively as part of the GIST clinical register. Relapse-free survival (RFS) was calculated from the date of GIST resection to the date of local recurrence, distant metastatic disease or last follow-up. Overall survival (OS) was calculated from the date of resection to the date of last follow-up or death. Survival analyses were performed using the Kaplan-Meier method and log-rank test. Multivariate Cox regression was performed to asses impact of mutational status on RFS and OS. Results: The primary tumor (PT) locations were: gastric (57.6%) vs non-gastric (42.4%). The median of tumor size was 7cm (0.5-33 cm). Mitotic index was ≤5 in 54.3%, &gt; 5 in 45.7%. Mutations in KIT gene exon 11 were as follow: del 557-558 in 22.7% or other (point mutations, other deletions or insertions) in 40.1% with similar rates in gastric and non-gastric GIST. KIT gene exon 9 dup 502-503 (7.2%) were more common in non-gastric vs gastric GIST (16.3% vs 0.6%). PDGFR D842V was observed in 26 patients (8.6%) while other mutations in PDGFRA gene in 17 (5.6%). The median follow-up was 25.1 months. Disease recurrence was observed in 124 cases (40.8%) resulting in median RFS of 84.4 (95%CI 48.3-120.5) months. The negative independent risk factors for RFS in univariate analysis were: primary tumor location, tumor size, mitotic index and KIT exon 9 dup 502-503 mutation (P &lt; 0.05). In the multivariate analysis independent predictive factors for RFS were mitotic index &gt; 5 (HR 4.38, 95%CI 2.82-6.78), PT location (HR 1.56, 95%CI 1.01-2.39). In multivariate analysis in patients with gastric GIST PDGFR D842V mutations were significantly correlated with better RFS (HR 0.16, 95%CI 0.04-0.61), what was not observed in non-gastric GIST. The median OS was 198.1 months. The negative independent risk factors for OS in univariate analysis were: primary tumor location, primary tumor size and KIT gene exon 9 dup 502-503 mutation. Mitotic index was also negative independent risk factors in a multivariate analysis (HR 1.70, 95%CI 1.15 -2.52). Conclusions: In the long-term analysis mutational status of primary resectable GIST is related to risk of relapse especially in gastric location, however it has no independent impact on overall survival. Genotype should be included in modern risk classification of GIST.

Primary Liver GIST Presenting as a Persistent Liver Abscess

Introduction: Primary liver GIST are very rare, there are only 34 cases reported in the literature; their origin is unknown but may be related to intersticial Cajal-like cells or from undifferentiated pluripotent mesenchymal stem cells that differentiate to the former. Methods: We present a case of a 56 year old woman that presented with a 4 day historia of abdominal pain with no other symptoms, liver tests, inflamatory markers and tumor markers where unremarkable. She has been previously been hospitilized for what appeared yo be a liver abscess wich was drained percutaneosly, and given a 4 week course of antibióticos. Results: Current imaging included CT that showed an ill defined cystic non-enhancing lesión in segments VI,V and VII of 8x6x7cm. MRI showed the same lesion with ill defined enhancement with contrast that suggested a liver neoplasic lesion. With this results a percutaneous liver biopsy was done that was compatible with a GIST tumor. Upper endoscopy and colonoscopy where negative, and because the patient persisted symptomatic an open liver resection of segments VI,V and VI was done, no other lesions where seen in the abdomen. Operative time was 240 minutes, 500cc blood loss, 3 postiperative days in the ICU and 5 days in the floor until discharge, no periopetative morbidity; follow up, was unremarkable awaiting Oncology consult to decide adyuvant treatment.PET-FDG scan was done wich was negative for malignant lesions. Conclusion: Primary liver GIST is very rare entity ; this report contributes to the understanding and presentation for ungoing studies.

KITlow Cells Mediate Imatinib Resistance in Gastrointestinal Stromal Tumor.

Gastrointestinal stromal tumor (GIST) is commonly driven by oncogenic KIT mutations that are effectively targeted by imatinib (IM), a tyrosine kinase inhibitor (TKI). However, IM does not cure GIST, and adjuvant therapy only delays recurrence in high-risk tumors. We hypothesized that GIST contains cells with primary IM resistance that may represent a reservoir for disease persistence. Here, we report a subpopulation of CD34+KITlow human GIST cells that have intrinsic IM resistance. These cells possess cancer stem cell-like expression profiles and behavior, including self-renewal and differentiation into CD34+KIThigh progeny that are sensitive to IM treatment. We also found that TKI treatment of GIST cell lines led to induction of stem cell-associated transcription factors (OCT4 and NANOG) and concomitant enrichment of the CD34+KITlow cell population. Using a data-driven approach, we constructed a transcriptomic-oncogenic map (Onco-GPS) based on the gene expression of 134 GIST samples to define pathway activation during GIST tumorigenesis. Tumors with low KIT expression had overexpression of cancer stem cell gene signatures consistent with our in vitro findings. Additionally, these tumors had activation of the Gas6/AXL pathway and NF-κB signaling gene signatures. We evaluated these targets in vitro and found that primary IM-resistant GIST cells were effectively targeted with either single-agent bemcentinib (AXL inhibitor) or bardoxolone (NF-κB inhibitor), as well as with either agent in combination with IM. Collectively, these findings suggest that CD34+KITlow cells represent a distinct, but targetable, subpopulation in human GIST that may represent a novel mechanism of primary TKI resistance, as well as a target for overcoming disease persistence following TKI therapy.

Neoadjuvant therapy for gastrointestinal stromal tumors: A propensity score‐weighted analysis

Retrospective and single arm prospective studies have reported clinical benefit with neoadjuvant imatinib for GISTs. In the absence of randomized phase III data, the impact of neoadjuvant systemic therapy (NAT) on survival compared to upfront resection (UR) remains unknown. We identified N=16,308 patients within the National Cancer Database (2004-2016) who underwent resection of localized GIST of the stomach, esophagus, small bowel, and colorectum, with or without ≥3 mon of NAT. Inverse probability of treatment weighting adjusted for covariable imbalance among treatment groups. We estimated the effect of NAT on overall survival with a weighted time-dependent Cox proportional hazards model, and on 90-day postoperative mortality and R0 resection with weighted logistic regressions. 865 (5.3%) patients received NAT, compared to 15,443 (94.7%) who underwent UR. Median NAT duration was 6.3 months. 53.7% of NAT patients were male vs. 48.6% of UR patients, 67.3% vs. 65.1% had primary gastric GIST, and 72.8% vs 49.7% were high-risk. NAT patients had larger tumors and higher mitotic index. >3 months of NAT was associated with a significant survival benefit (weighted HR 0.85 (0.80-0.91)). 90-day postoperative mortality rate was 4/865 (0.5%) among NAT patients vs. 346/15,443 (2.2%). NAT was associated with lower odds of 90-day postoperative mortality. R0 resection rate was not significantly different between groups. In conclusion, despite higher risk features among NAT patients, this analysis suggests that NAT for localized GIST is associated with a modest survival benefit and lower risk of 90-day postoperative mortality, with no difference in likelihood of achieving an R0 resection. This article is protected by copyright. All rights reserved.

Primary Appendiceal Gastrointestinal Stromal Tumor: A Case of an Incidental Tumor

Abstract Introduction/Objective Gastrointestinal stromal tumors (GISTs) are rare with an approximate prevalence of 2%. Though rare, they are the most common mesenchymal neoplasm of the gastrointestinal tract. They commonly occur in the stomach (50-60%), small intestine (20-30%), large intestine and esophagus (&amp;lt;10%). GISTs arising in the appendix are very rare, with less than 20 cases reported in the English literature to date. The clinical presentation varies from appendicitis-like symptoms to incidental findings on imaging, during surgery for other diseases or at autopsy. The differential diagnosis of GIST from other stromal tumors is often difficult on hematoxylin and eosin (H&amp;E) examination alone. The use of immunohistochemistry (IHC) plays a key role in confirming the diagnosis. GISTs can be graded based on a four-tier risk stratification system, including high, intermediate, low and very low risk, taking size tumor and mitotic activity into consideration. Most of the previously reported cases of primary appendiceal GIST were low or very low risk but one case of malignant GIST arising in the appendix has been reported. Methods We present the case of a 65-year-old male with a slightly thickened appendix and fluid in the distal aspect incidentally found on computer tomography (CT) scan for diverticulitis workup. An appendectomy with adequate was performed. The gross specimen revealed a 0.2-0.4 cm thick wall with no gross perforations or masses. Histologically, the tumor measured 0.8 cm and was composed of spindle cells with no nuclear atypia and absent to low mitotic activity. The IHC profile of the tumor was positive for CD117, DOG1 and CD34. A diagnosis of Gastrointestinal stromal tumor, low grade was rendered. Conclusion We endeavor to highlight the importance of considering GIST in the differential diagnosis in patients with nonspecific symptoms and/or atypical image findings of the appendix especially in ruling out a possible malignant GIST.

Transanal endoscopic microsurgery with alternative neoadjuvant imatinib for localized rectalgastrointestinal stromal tumor: a single center experience with long-term surveillance.

Transanal endoscopic microsurgery (TEM) is widely used in the treatment of local rectal lesions and helps avoid radical surgery. This study evaluated the management and outcome in a long-term followed cohort of patients with localized rectal GIST underwent TEM with alternative neodajuvant imatinib (nIM). A retrospective cohort study was undertaken of patients identified from a case database at Department of General Surgery, Peking Union Medical College Hospital (PUMCH) over a continuous period, from January 2006 to December 2017. Over 12years, 42 patients presented with a primary rectal GIST in PUMCH. Median age was 49 (range 27-77) years. Neoadjuvant imatinib (nIM) therapy was used in 16 patients, significantly reducing mean tumor size from 4.41 to 2.46cm (p < 0.001) and mitotic index (p = 0.041). All of these patients underwent TEM with no tumor rupture, nIM therapy enabled sphincter-preserving surgery to be undertaken in 16 (16/42) patients who would otherwise have required abdominoperineal resection or pelvic exenteration for tumor clearance and all patients (42/42) achieve R0 resection and negative margin. Imatinib was also used as postoperative adjuvant treatment in 15 patients with high-risk GIST. Median follow-up was 77 (range 14-144) and overall survival is 100%. In 42 patients, Local recurrence (LR) occurred in 3 of 42 patients and 1 of 42 patients developed distant metastasis (DM) in 112months after TEM. In the univariate analysis, mitotic index (p = 0.028), NIH risk categories (p = 0.047) were predictive feature of local relapse. The application of nIM significantly decreased tumor size in large localized rectal GIST, which permitted TEM to preserve sphincter. The TEM procedure with alternative neoadjuvant imatinib therapy is a practicable treatment for patients with rectal GIST to preserve anus and have satisfied anal function.

Neoadjuvant therapy for localized gastrointestinal stromal tumors (GISTs): A propensity score weighted analysis.

e23516 Background: Retrospective and single-arm prospective studies have reported clinical benefit associated with receipt of neoadjuvant imatinib for GISTs. In the absence of randomized phase III data, the impact of neoadjuvant systemic therapy (NAT) on survival, in comparison to upfront resection, remains unknown. Methods: We identified N = 14,402 patients with complete clinical, demographic, treatment and pathologic data within the National Cancer Database (2004-2016) who underwent resection of localized GIST of the stomach, esophagus, small bowel, and colorectum, with or without ≥3 months of NAT. Inverse probability of treatment weighting (IPTW) was used to adjust for covariable imbalance among treatment groups, with the propensity score estimated by logistic regression. The effect of NAT on overall survival was estimated with a weighted time-dependent Cox proportional hazards model. A weighted logistic regression was used to estimate the effect of NAT on 90-day postoperative mortality and R0 resection. Results: 759 (5.3%) patients received NAT followed by resection, compared to 13,643 (94.7%) who underwent upfront resection. Median length of NAT was 6.3 months. 53% of NAT patients were male vs. 49% of UR patients, 68% vs. 66% had primary gastric GIST, and 73% vs 49% were high risk. Patients receiving NAT had larger tumors (p &lt; 0.001) and higher mitotic index (p = 0.003). There was a significant survival benefit associated with receipt of NAT (table). 90-day postoperative mortality rate was 3/759 (0.4%) among NAT patients vs. 307/13,643 (2.3%) UR patients. Receipt of NAT was significantly associated with lower odds of 90-day postoperative mortality (table). Of the 13,562 patients with information on margin status, the R0 resection rate was 635/716 (88.7%) for the neoadjuvant group vs. 11,823/12,846 (92%), with no significant difference between treatment groups (table). Conclusions: After adjustment for imbalance in prognostic and demographic factors, this analysis demonstrates that receipt of NAT for localized GIST is associated with a modest overall survival benefit. Although NAT patients had higher risk features, NAT was associated with a lower risk of 90-day postoperative mortality, with no difference in likelihood of achieving an R0 resection. [Table: see text]

Anti-KIT DNA Aptamer for Targeted Labeling of Gastrointestinal Stromal Tumor.

Gastrointestinal stromal tumor (GIST), the most common sarcoma, is characterized by KIT protein overexpression, and tumors are frequently driven by oncogenic KIT mutations. Targeted inhibition of KIT revolutionized GIST therapy and ushered in the era of precision medicine for the treatment of solid malignancies. Here, we present the first use of a KIT-specific DNA aptamer for targeted labeling of GIST. We found that an anti-KIT DNA aptamer bound cells in a KIT-dependent manner and was highly specific for GIST cell labeling in vitro Functionally, the KIT aptamer bound extracellular KIT in a manner similar to KIT mAb staining, and was trafficked intracellularly in vitro The KIT aptamer bound dissociated primary human GIST cells in a mutation agnostic manner such that tumors with KIT and PDGFRA mutations were labeled. In addition, the KIT aptamer specifically labeled intact human GIST tissue ex vivo, as well as peritoneal xenografts in mice with high sensitivity. These results represent the first use of an aptamer-based method for targeted detection of GIST in vitro and in vivo.

Polyneoplasia associated with gastrointestinal stromal tumor: literature review and case report

The purpose of the study was to demonstrate a rare clinical case of polyneoplasia associated with GIST, combining three malignant neoplasms of different nosological affiliation and different tissue origin. Scientific interest is caused by the need to study polyneoplasia associated with Gist, which can be explained by the concept of Rodriquenz M.G. et al. (2016), suggesting the special role of a solitary GisT in the potential development of polyneoplasia. Material and Methods . The search for relevant sources was carried out in the Medline, Cochrane Library, Elibrary systems, includibg publications from January 2009 to October 2019. Of the 507 studies, 21 were used to write a systematic review. Results. In the vast majority of cases, polyneoplasia is represented by two malignant neoplasms in a single patient. Primary multiple metachronous and primary multiple synchronous tumors with three or more tumors are observed very rarely. Among all multiple primary tumors, our attention was drawn to polyneoplasia containing GisT. A neoplasm associated with a GisT is localized mainly in the gastrointestinal tract, and also occurs in the organs of the urinary system, female genital system, thyroid gland, breast, lungs, and testicles. Conclusion. This clinical case is a rather rare phenomenon of polyneoplasia associated with GisT of rectum, which combines three malignant neoplasms. It should be noted that primary Gist in the rectum occurs in 4% of cases.

Oncological Outcome After Diagnostic Biopsies in Gastrointestinal Stromal Tumors: A Retrospective Cohort Study.

To analyze whether the route of preoperative biopsy influences oncological outcome in GIST patients. Preoperative biopsies are widely used for diagnosing GIST. Little is known about the risk of tumor seeding after different routes of biopsy. Patients who underwent resection of a primary GIST between 1996 and 2014 were identified from 2 databases from 2 tertiary referral centers. Survival data were obtained using the Kaplan-Meier method. Possible confounders were identified using Cox regression analysis. The primary endpoint was local recurrence free survival (RFS) and the secondary endpoint was DSS. A total of 228 patients were included, with a median age of 62 years (range 17-86) and a median follow-up time of 53 months (range 1-204). From these patients, 42 patients did not have a biopsy (18%), 70 underwent a transcutaneous biopsy (31%), and 116 a transluminal biopsy (51%). A total of 42 patients (19.0%) had a local and/or distant recurrence. From the 70 patients with a transcutaneous biopsy, only 1 patient developed a needle tract recurrence (1.4%). Local RFS and DSS were both significantly shorter in the transcutaneous biopsy group on univariate analysis compared to the other groups; however, in multivariate analysis the route of biopsy did not influence local RFS (P = 0.128) or DSS (P = 0.096). Transluminal or transcutaneous biopsies for diagnosing GIST do not significantly alter the risk of local recurrent disease or DSS in multivariate Cox regressions. The risk of needle tract seeding after transcutaneous biopsy was low.

Molecular and Clinicopathological Features of Gastrointestinal Stromal Tumors in Vietnamese Patients.

BackgroundGastrointestinal stromal tumors (GISTs) are the most frequent mesenchymal neoplasms of the gastrointestinal tract. Management of GIST patients is currently based on clinicopathological features and associated genetic changes. However, the detailed characteristics and molecular genetic features of GISTs have not yet been described in the Vietnamese population.MethodsWe first identified 155 patients with primary GIST who underwent surgery with primary curative intent between 2011 and 2014 at University Medical Center at Ho Chi Minh City, Vietnam. We evaluated the clinicopathological features and immunohistochemical reactivity to p53 and Ki-67 in these patients. Additionally, KIT genotyping was performed in 100 cases.ResultsThe largest proportion of GISTs was classified as high-risk (43.2%). Of the 155 GISTs, 52 (33.5%) were positive for Ki-67, and 58 (37.4%) were positive for p53. The expression of Ki-67 and p53 were correlated with mitotic rate, tumor size, risk assessment, and tumor stage. Out of 100 GIST cases, KIT mutation was found in 68%, of which 62 (91.2%) were found in exon 11, two (2.9%) in exon 9, and four (5.8%) in exon 17. No mutation in exon 13 was identified. Additionally, KIT mutations did not correlate with any clinicopathological features.ConclusionsThe expression of Ki-67 and p53 were associated with high-risk tumors. Mutations in exon 11 were the most commonly found, followed by exon 17 and exon 9. Additionally, KIT mutation status was not correlated with any recognized clinicopathological features.

Resection of GIST in the duodenum and proximal jejunum: A retrospective analysis of outcomes

IntroductionGastrointestinal stromal tumors (GISTs), with a primary occurrence in the duodenum and proximal jejunum, are rare and treatment is poorly understood. This study aimed to evaluate the main factors influencing the prognosis of GIST resection in this complex anatomical structure. Materials and methodsThis retrospective study included 47 patients who underwent surgery for primary GIST of the duodenum (20) and proximal jejunum (27) between 2012 and 2017. Perioperative clinical data as well as relapse and survival information were collected. ResultsAll patients underwent negative margin resection (R0) of duodenal and proximal jejunum GISTs. Complications occurred more frequently in treatment of duodenal GISTs than proximal jejunum GISTs (p = 0.003). GISTs in D3 (the 3rd portion of duodenum) were related to larger tumor size (p = 0.001), higher probability of severe complication rate (p = 0.042), longer hospital stays (p = 0.023) and fasting time (p = 0.020). More complications were found for patients with digestive reconstruction than limited resection (p = 0.010). Additionally, patients with a tumor mass larger than 5 cm or a mitotic index greater than 5 mitoses/50 HPFs showed poorer therapeutic outcomes. The 1- and 3-year overall survival was 97.9% and 86.1%, respectively and were not influenced by operation type (p = 0.061) or GIST position (p = 0.447). ConclusionWith negative operational margins, limited resection is a safe and feasible procedure for duodenal and proximal jejunum GIST patients and unnecessary digestive reconstruction should be avoided. Considering the severe complication rate, resection for GISTs in D3 should be performed with care.

KIT exon 11 and PDGFRA exon 18 gene mutations in gastric GIST: proposal of a short panel for predicting therapeutic response

BackgroundGIST is the most common mesenchymal tumor of gastrointestinal tract and is more frequent in stomach. Its main mutations affect KIT and PDGFRA genes. Full genetic analysis panels are currently used to study mutations in GIST and other tumors. Considering that in gastric GIST KIT gene mutations in exon 11 are sensitive to IM whereas PDGFRΑ gene mutations in exon 18 (D842V) are resistant to the same drug, the aim of this study is to focus on these two molecular targets as a short alternative panel for predicting therapeutic response in gastric GIST which might optimize resources.MethodsThe genotypes of 38 cases of primary GIST were determined by performing bidirectional DNA sequencing.ResultsExon 11 of KIT gene showed mutations in 65.3% and the exon 18 of PDGFRA gene showed 9% of cases. So it was possible to determine a subgroup of tumors which presented mutations in KIT exon 11 and PDGFRA exon 18.ConclusionConsidering all of the foregoing analyzed globally, the application of short panel has impact on the cost and time of release of results to the physician, allowing a rapid approach to patients eligible for treatment with the target therapy.

Peritoneal dissemination of recurrent small intestine primary GIST, successfully diagnosed by diffusion-weighted imaging

Peritoneal dissemination of recurrent small intestine primary GIST, successfully diagnosed by diffusion-weighted imaging