Duodenal gastrointestinal stromal tumors: Review on clinical and surgical aspects

Cavallaro, Giuseppe; Polistena, Andrea; D'Ermo, Giuseppe; Pedullà, Giuseppe; Toma, Giorgio De

doi:10.1016/j.ijsu.2012.08.015

Cited by 26 publications

(28 citation statements)

References 25 publications

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“…Furthermore, the median size of duodenal GISTs in our series was 4.7 cm. Similarly, most authors report a smaller size of tumor (4.0 to 5.0 cm) for duodenal GISTs compared with gastric and small bowel GISTs [6,8,11]. Interestingly, we noted that patients who ultimately required PD were more likely to present with a larger tumor and more commonly presented with a tumor in the second portion of the duodenum compared with LR.…”

Section: Discussionsupporting

confidence: 62%

Pancreaticoduodenectomy versus local resection in the treatment of gastrointestinal stromal tumors of the duodenum

Zhou

Zhang

et al. 2013

World J Surg Onc

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BackgroundGastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms. However, duodenal GISTs compromise a small and rare subset and few studies have focused on them. We evaluated the surgical management of patients with duodenal GISTs treated by pancreaticoduodenectomy (PD) versus local resection (LR) in our institution and analyzed the postoperative outcomes.MethodsThis was a retrospective review of patients with duodenal GISTs managed in our institution from January 2006 to January 2012. Clinicopathologic findings and disease-free survival (DFS) of duodenal GIST patients were analyzed.ResultsA total of 48 patients were selected. The most common presentation was bleeding (60.4%), and the second portion of the duodenum (35.4%) was the most common dominant site. Of the patients, 34 (70.8%) underwent LR while 14 (29.2%) underwent PD. The surgical margins for all studied patients were free. Patients who ultimately underwent PD were more likely to present with a larger tumor (median size: PD, 6.3 cm vs LR, 4.0 cm; P = 0.02) and more commonly presented with a tumor in the second portion of the duodenum (second portion: PD, 64.3% vs LR, 23.5%; P = 0.007). The tumors treated by PD had a higher grade of risk compared with LR as defined by National Institutes of Health (NIH) criteria (P = 0.019). PD was significantly associated with a longer operation time and a longer hospital stay compared to LR (P < 0.001 and P = 0.001, respectively). In our study, the median follow-up period was 36 months (range: 0 to 81 months). The 1- and 3-year DFS was 100% and 88%, respectively. From multivariable analysis, the only significant factor associated with a worse DFS was an NIH high risk classification (hazard ratio = 4.24).ConclusionsThe recurrence of duodenal GIST was correlated to tumor biology rather than type of operation. PD was associated with a longer hospital stay and longer operation time. Therefore, LR with clear surgical margins should be considered a reliable and curative option for duodenal GIST and PD should be reserved for lesions not amenable to LR.

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Section: Discussionsupporting

confidence: 62%

Pancreaticoduodenectomy versus local resection in the treatment of gastrointestinal stromal tumors of the duodenum

Zhou

Zhang

et al. 2013

World J Surg Onc

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“…11, 25–27 Achieving wide margins in the duodenum is not always possible; margins of fewer than 5 mm after resection of duodenal tumors are not uncommon. 9 We found that only 84% of LR were R0 resections versus 100% in the pancreaticoduodenectomy group.…”

Section: Discussionmentioning

confidence: 99%

Surgical Strategy and Outcomes in Duodenal Gastrointestinal Stromal Tumor

et al. 2016

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Introduction The surgical management of duodenal gastrointestinal stromal tumors (DGIST) is poorly characterized. Limited resection may be technically feasible and oncologically safe, but anatomical considerations may compromise the resection margins due to the proximity of critical structures, thereby necessitating more extensive resections such as pancreaticoduodenectomy. Methods Patients undergoing surgery for DGIST at 2 institutions from 1994–2014 were identified. Clinicopathologic and survival data were analyzed to compare outcomes in patients treated with limited or radical resection. Results Sixty patients underwent surgery for DGIST. Pancreaticoduodenectomy was performed in 38% while the rest underwent limited resections. The most common type of limited resection was wedge resection and primary closure (49%) followed by segmental resection with an end-to-end or side-to-side duodenojejunostomy (27%). The pancreaticoduodenectomy group tended to have larger tumors with the majority located in D2/3 (87%) and at the mesenteric border (91%). The pancreaticoduodenectomy group also had significantly greater intraoperative blood loss, longer operative time, longer hospital stay, and higher 90-day morbidity and readmission rates. The 5- year relapse-free survival (RpFS), recurrence-free survival (RFS), and overall survival (OS) for the pancreaticoduodenectomy vs. limited resection were 81% vs. 56% (p = 0.05), 64% vs. 53% (p = 0.5), and 76% vs. 72% (p = 0.6), respectively. A surgical algorithm based on the location and size of the tumor is proposed. Conclusion Limited resection of DGIST is safe, but may be associated with lower 5-year relapse-free survival. Pancreaticoduodenectomy is recommended for selected patients with DGIST when an R0 resection cannot be performed without removing the ampulla or part of the pancreas.

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“…The majority of GISTs (gastrointestinal stromal tumours) possess mutually exclusive mutations in platelet‐derived growth factor subunit A (PDGFRA) or KIT, which constitutively activate the encoded receptor tyrosine kinases (RTKs) to control the response to imatinib treatment and lead to tumorigenesis . In adults, 10%‐15% of GISTs exhibit wild‐type KIT and PDGFA genes but may bear mutated neurofibromatosis type 1 (NF1), BRAF, or succinate dehydrogenase (SDH) genes .…”

Section: Introductionmentioning

confidence: 99%

Bromodomain and extraterminal domain inhibitor enhances the antitumor effect of imatinib in gastrointestinal stromal tumours

Sun²,

et al. 2020

J Cellular Molecular Medi

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In gastrointestinal stromal tumours (GISTs), the function of bromodomain‐containing 4 (BRD4) remains underexplored. BRD4 mRNA abundance was quantified in GISTs. In the current study, we investigated the role of BRD4 in GISTs. Our results show a significant enhancement in BRD4 mRNA and a shift from very low‐risk/low‐risk to high‐risk levels as per NCCN specifications. Overexpression of BRD4 correlated with unfavourable genotype, nongastric location, enhanced risk and decreased disease‐free survival, which were predicted independently. Knockout of BRD4 in vitro suppressed KIT expression, which led to inactivation of the KIT/PI3K/AKT/mTOR pathway, impeded migration and cell growth and made the resistant GIST cells sensitive to imatinib. The expression of KIT was repressed by a BRD4 inhibitor JQ1, which also induced myristoylated‐AKT‐suppressible caspases 3 and 9 activities, induced LC3‐II, exhibited dose‐dependent therapeutic synergy with imatinib and attenuated the activation of the PI3K/AKT/mTOR pathway. In comparison with their single therapy, the combination of JQ1/imatinib more efficiently suppressed the growth of xenografts and exhibited a reduction in KIT phosphorylation, a decrease in Ki‐67 and in the levels of phosphorylated PI3K/AKT/mTOR and enhanced TUNEL staining. Thus, we characterized the biological, prognostic and therapeutic implications of overexpressed BRD4 in GIST and observed that JQ1 suppresses KIT transactivation and nullifies the activation of PI3K/AKT/mTOR, providing a potential strategy for treating imatinib‐resistant GIST through dual blockade of KIT and BRD4.

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Duodenal gastrointestinal stromal tumors: Review on clinical and surgical aspects

Cited by 26 publications

References 25 publications

Pancreaticoduodenectomy versus local resection in the treatment of gastrointestinal stromal tumors of the duodenum

Pancreaticoduodenectomy versus local resection in the treatment of gastrointestinal stromal tumors of the duodenum

Surgical Strategy and Outcomes in Duodenal Gastrointestinal Stromal Tumor

Bromodomain and extraterminal domain inhibitor enhances the antitumor effect of imatinib in gastrointestinal stromal tumours

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