Treatment Of Gastrointestinal Stromal Tumors Research Articles

1634P The efficacy of continuous circulatory hyperthermic intraperitoneal chemotherapy (C-HIPEC) following cytoreductive surgery for metastatic gastrointestinal stromal tumors (GISTs)

Early reports discussed the prognostic factors of patients with metastatic GIST treated with cytoreductive surgery (CRS). However, the role of C-HIPEC, after CRS, for the treatment of peritoneal metastatic GIST remains unknown. A retrospective analysis of patients with peritoneal metastatic GIST treated with CRS + C-HIPEC combined with targeted therapy from a single institution was performed. C-HIPEC was introduced 1 or more days after CRS, with mitoxantrone, or doxorubicin with cisplatin. Overall survival (OS), and progression free survival (PFS) from time of surgery was determined. One-to-one propensity score matching (PSM) analyses were conducted to balance selection bias. Univariate and multivariate analysis were performed using a Cox proportional-hazards model. Between 2007 and 2018, we performed 104 operations on 87 patients with peritoneal metastatic GIST. C-HIPEC was conducted following 35 operations. After a median follow up of 23 months, the median OS and PFS were 40 months and 16 months. After PSM, both C-HIPEC group and non-C-HIPEC group had 28 operations. Either the median OS or PFS was not significantly difference in both groups, with 35 months of C-HIPEC vs 37 months of non-C-HIPEC (HR = 1.22 [95%CI: 0.56-2.67], P = 0.6187)，and 13 months in both groups( HR = 0.99 [95%CI: 0.53-1.85], P = 0.9865). Among all patients, 30 days post-operative grade III-IV morbidity rate was 16.3% (C-HIPEC 14.3% and non-C-HIPEC 17.4%, respectively, [P = 0.901]). Multifocal progression, with liver and/or extra-abdominal metastasis, tumor rupture and diameter of resected tumors ≥ 6.5cm were prognostic of worse OS. Multifocal progression, with liver and/or extra-abdominal metastasis and mitotic index >5/50 HPF were associated with worse PFS. C-HIPEC is safe to perform after CRS for metastatic GISTs. However, lacking of infusional regimen of targeted therapy, C-HIPEC using traditional chemotherapy medications did not increase survival benefits compared to CRS alone.

Gastrointestinal stromal tumor of the cecum with disseminated omental and pancreatic lesions in a dog treated with surgical resection and adjuvant imatinib mesylate chemotherapy

A 10-year-old female mongrel dog presented with abdominal distension. Physical, radiographic, and ultrasound examinations detected an intestinal mass and ascites. Laparotomy revealed that the mass originated from the cecum and disseminated in the omentum and pancreas. Surgical resection of the mass and disseminated lesions was performed. Histopathological examination revealed the mass and lesions to be gastrointestinal stromal tumors (GISTs). Imatinib mesylate (10 mg/kg/sid) was administered for 355 days postoperatively. The dog survived for > 855 days with no recurrence and metastasis. Adjuvant chemotherapy with imatinib mesylate may be an effective treatment for GIST.

Abstract 5181: Therapeutic targeting of GPR20, selectively expressed in gastrointestinal stromal tumor (GIST), with DS-6157a, an antibody-drug conjugate (ADC)

Abstract More than 85% of GISTs are driven by activating mutations in KIT proto-oncogene receptor tyrosine kinase (KIT) or platelet-derived growth factor receptor alpha (PDGFRA). Currently, the only approved treatments for GIST are KIT directed tyrosine kinase inhibitors (TKIs). However, treatment with approved TKIs eventually results in disease progression most often due to the development of secondary resistance mutations in KIT. In addition, these agents have limited activity in PDGFRA mutant GIST and KIT/PDGFRA wild type (WT) GIST as primary therapy. Therefore, it is essential to develop novel therapeutic strategies with different modes of action in advanced GIST. G protein-coupled receptor 20 (GPR20) is an orphan GPCR selectively and abundantly expressed in GIST. GPR20 expression is regulated by FOXF1 and ETV1, transcription factors that play critical roles in KIT-driven GIST initiation, proliferation, and survival. We hypothesize that GPR20 is a potential therapeutic target for ADC development for the treatment of GIST. In this study, 1) GPR20 and KIT protein expression was assessed by IHC staining on GIST samples from DFCI (n=144) and NCCHE (n=100) as well as on normal and malignant tissue microarrays obtained commercially, and 2) an anti-GPR20 ADC (DS-6157a) was generated to evaluate antitumor activity in GIST models and to assess safety. GPR20 was expressed in more than 88% of the GIST samples analyzed, with higher expression levels in samples that: (I) received multiple treatment lines compared to naïve/early treated samples, (II) expressed higher KIT levels, (III) were small intestinal GIST, and/or (IV) had no KIT mutation, including succinate dehydrogenase (SDH) deficient GIST and neurofibromatosis type 1 (NF1)-associated GIST. The interstitial cells of Cajal were the only normal cells positive for GPR20. Normal mast cells expressed KIT but not GPR20. DS-6157a is an ADC composed of a humanized anti-GPR20 antibody, a Gly-Gly-Phe-Gly tetra-peptide-based linker, and a DNA topoisomerase I (TOP1) inhibitor Dxd. DS-6157a exhibited GPR20 expression-dependent cell growth-inhibitory activity and induced tumor regression with dosing at 3 to 10 mg/kg in multiple GIST xenograft models. In addition, DS-6157a showed antitumor activity in a GIST patient-derived xenograft model that was resistant to imatinib, sunitinib, and regorafenib. In vitro, DS-6157a induced TOP1 inhibitor-associated markers of DNA damage (phosphorylation of Chk1) and apoptosis (cleaved PARP) in GPR20 expressing cells. In preclinical toxicology studies using rats and cynomolgus monkeys, the pharmacokinetics and safety profile of DS-6157a were favorable at up to 200 mg/kg and 30 mg/kg, respectively. These data support the clinical development of DS-6157a as a potential novel GIST therapy with activity in patients that are resistant, refractory, or intolerant to approved TKIs. Citation Format: Kenji Iida, Amr H. Abdelhamid, Akiko Kawano Nagatsuma, Tomoko Shibutani, Satoru Yasuda, Michiko Kitamura, Chiharu Hattori, Manabu Abe, Jun Hasegawa, Takuma Iguchi, Tsuyoshi Karibe, Takashi Nakada, Koichiro Inaki, Reiko Kamei, Yuki Abe, Jessica L. Andersen, Sandro Santagata, Matthew L. Hemming, Suzanne George, Toshihiko Doi, Atsushi Ochiai, George D. Demetri, Toshinori Agatsuma. Therapeutic targeting of GPR20, selectively expressed in gastrointestinal stromal tumor (GIST), with DS-6157a, an antibody-drug conjugate (ADC) [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5181.

LIX1 regulates YAP activity and controls gastrointestinal cancer cell plasticity.

Gastrointestinal stromal tumours (GISTs), the most common mesenchymal neoplasm of the gastrointestinal tract, result from deregulated proliferation of transformed KIT‐positive interstitial cells of Cajal that share mesenchymal progenitors with smooth muscle cells. Despite the identification of selective KIT inhibitors, primary resistance and relapse remain a major concern. Moreover, most patients develop resistance partly through reactivation of KIT and its downstream signalling pathways. We previously identified the Limb Expression 1 (LIX1) gene as a unique marker of digestive mesenchyme immaturity. We also demonstrated that LIX1 regulates mesenchymal progenitor proliferation and differentiation by controlling the Hippo effector YAP1, which is constitutively activated in many sarcomas. Therefore, we wanted to determine LIX1 role in GIST development. We found that LIX1 is strongly up‐regulated in GIST samples and this is associated with unfavourable prognosis. Moreover, LIX1 controls GIST cell proliferation in vitro and in vivo. Upon LIX1 inactivation in GIST cells, YAP1/TAZ activity is reduced, KIT (the GIST signature) is down‐regulated, and cells acquire smooth muscle lineage features. Our data highlight LIX1 role in digestive mesenchyme‐derived cell‐fate decisions and identify this novel regulator as a target for drug design for GIST treatment by influencing its differentiation status.

A pictorial review on clinicopathologic and radiologic features of duodenal gastrointestinal stromal tumors.

Duodenal gastrointestinal stromal tumors (GISTs) are rare, and studies on their management are not sufficient. Owing to the complex anatomy of the duodenum and pancreatic head, GISTs can be misdiagnosed as pancreatic head tumors. Surgical resection is the first treatment for localized duodenal GISTs; thus, noninvasive imaging is important for the diagnosis and treatment of GISTs. Computed tomography, magnetic resonance imaging and endoscopic ultrasonography findings can be helpful for the diagnosis of duodenal GISTs and can help differentiate GISTs from other adjacent tumors.

Avapritinib: novel hope for patients with metastatic gist with PDGFRA exon 18 mutation

Gastrointestinal stromal tumors (GISTs) are mesenchymal neoplasms of the gastrointestinal tract associated with high rates of malignant transformation. The activating mutations in platelet-derived growth factor receptor A (PDGFRA) have been linked to the development of GISTs, and up to approximately 10% of GIST cases involve mutations of this gene. Current treatment options for metastatic GIST are minimal, mainly trusting on tyrosine kinase inhibitors (TKIs) such as Imatinib, Sunitinib and Regorafenib. However, eventually, most patients develop resistance to TKIs, usually due to the acquisition of secondary mutations. Moreover, 5-6% of patients with unresectable of metastatic GIST have the primary PDGFRA D842V mutation, which makes it resistant to all approved treatment options. Avapritinib, a potent and selective TKI of KIT and PDGFRA activation loop mutants. The drug demonstrates anti-tumor activity by inhibiting the autophosphorylation of KIT D816V and PDGFRA D842V, thereby terminating the downstream signalling. The drug is available in oral formulation with a recommended dosage of 300 mg once daily. The onset of Avapritinib is fast, shows rapid absorption and linear pharmacokinetics. Most common adverse reactions seen are edema, fatigue, abdominal pain, and neurocognitive defects. Clinical trials for Avapritinib have been positive, and results suggest that the drug may be a new safe and effective option for metastatic GIST treatment. With Blueprint Medicines having already received US FDA approval in January 2020, Avapritinib may soon be an addition to the mounting armoury of drugs against metastatic GIST harbouring PDGFRA exon 18 mutation.

Ripretinib: First Approval.

Ripretinib (QINLOCK™) is a novel type II tyrosine switch control inhibitor being developed by Deciphera Pharmaceuticals for the treatment of KIT proto-oncogene receptor tyrosine kinase (KIT)-driven and/or platelet derived growth factor receptor A (PDGFRA)-driven cancers, including gastrointestinal stromal tumour (GIST). Ripretinib inhibits KIT and PDGFRA kinase, including wild-type, primary and secondary mutations, as well as other kinases, such as PDGFRB, TIE2, VEGFR2 and BRAF. In May 2020, oral ripretinib received its first approval in the USA for the treatment of adult patients with advanced GIST who have received prior treatment with ≥ 3 kinase inhibitors, including imatinib. The US FDA, Health Canada and the Australian Therapeutic Goods Administration collaborated on the review of the ripretinib new drug application in this indication as part of Project Orbis; regulatory review in Australia and Canada is ongoing. Clinical development for GIST, solid tumours and systemic mastocytosis is underway in several countries worldwide. This article summarizes the milestones in the development of ripretinib leading to this first approval for the treatment of advanced GIST.

Laparoscopic Limited Resection for Duodenal Gastrointestinal Stromal Tumors

BackgroundLaparoscopic surgery may be a suitable treatment for gastrointestinal stromal tumors (GISTs) in terms of oncological feasibility and being minimally invasive. Case series of laparoscopic resection for duodenal GISTs have not been reported in detail, so in this report, the detail of laparoscopic surgeries for duodenal GISTs is summarized. MethodsThis is a single-center retrospective case series of six consecutive patients with duodenal GISTs who underwent laparoscopic limited resection of the duodenum between 2003 and 2019. ResultsTumors were located within the first portion in three patients, the second portion in two patients, and the third portion in one patient. Median tumor size was 25 mm. Four patients underwent a laparoscopic and endoscopic full-thickness resection with primary closure, one patient underwent a laparoscopic wedge resection, and one patient underwent a laparoscopic segmental duodenectomy with Roux-en-Y gastrojejunostomy. Median blood loss was minimal (10 ml) with median operative time of 2 h, and there were no conversions to open surgery. There were no intraoperative or postoperative complications. All patients underwent curative resection with negative surgical margins, and none had recurrence of their duodenal GISTs. All patients were alive at the end of the follow-up period of 54 months. ConclusionLaparoscopic limited resection is a feasible, safe, and ideal treatment procedure for duodenal GISTs in terms of short- and long-term surgical outcomes.

Robotic surgery for gastric gastrointestinal stromal tumors: A single center case series.

The aim of surgical treatment of gastrointestinal stromal tumors (GIST) is a microscopically complete resection. Initial indications for laparoscopic surgery were limited to smaller tumors, in favorable locations. Over time, indications for minimal invasive surgery (MIS) have expanded, however concerns remain when considering resection of larger GISTs. Our aims were to assess the utility of robotic resection of gastric GISTs for challenging tumors. GIST resections, in this study were performed using the Intuitive Da Vinci Surgical Xi System. GIST's were considered challenging if tumor size was >50 mm at the time of surgery and/or the location of the tumor was type II, III, or IV using Privette/Al-Thanai classification. Robotic resections were performed on 12 consecutive patients, 83% were considered challenging cases, 6 out of 12 for location and 5 out of 12 for size. Initial median tumor size on imaging was 53.7 mm, and post-imatinib was 45.8 mm. All tumors were removed with clear margins (R0) via wedge resections, with no complications. Median operative time was 192 minutes (95-250). Length of hospital stay was 2 days (2-6). Robotic resection of gastric GIST's appears oncologically safe, and may expand the benefits of MIS to a greater cohort of complex cases.

Laparoscopic gastrectomy with lymph node dissection for the treatment of remnant stomach gastrointestinal stromal tumors in incomplete-type Carney\u2019s triad: a case report

BackgroundWe report a rare case of gastrointestinal stromal tumors (GISTs) in Carney’s triad, successfully treated using laparoscopic gastrectomy with lymph node dissection after chemotherapy.Case presentationA 21-year-old woman presented to our hospital for treatment of recurrent GISTs. The patient had been admitted for treatment 11 years prior, with black stools being the chief presenting complaint at that time. On examination at that time, multiple submucosal tumors in the pyloric antrum and multiple pulmonary tumors had been observed. She underwent open partial gastrectomy, and the diagnosis of GISTs was confirmed. She was administered tyrosine kinase inhibitors to treat lung metastases from 2 months after surgery. Due to the increasing size of the lung tumors, a right upper lobectomy was performed 9 years after the index gastric surgery. Histopathological examination of the lung specimen, in combination with re-examination of the gastric specimens, was indicative of incomplete-type Carney’s triad. Eleven years after the index gastric surgery, multiple GISTs were observed in her entire stomach. Tumor biopsy revealed a succinate dehydrogenase deficiency, confirming the diagnosis of recurrent GISTs. For treatment, the patient underwent laparoscopic completion gastrectomy, with D1 plus lymph node dissection.ConclusionThis is a first case report of completion gastrectomy performed laparoscopically for the treatment of GISTs associated with incomplete-type Carney’s triad. The recurrent GISTs developed over a protracted period of 11 years from the index gastric surgery to tumor recurrence.

Gastrointestinal Stromal Tumors of the Small Intestine: Progress in Diagnosis and Treatment Research.

In recent years, the diagnosis and treatment of gastrointestinal stromal tumors (GISTs) of the small intestine have been a hot topic due to their rarity and non-specific clinical manifestations. With the development of gene and imaging technology, surgery, and molecular targeted drugs, the diagnosis and treatment of GISTs have achieved great success. For a long time, radical resection was prioritized to treat GISTs of the small intestine. At present, preoperative tumor staging is a novel treatment for unresectable malignant tumors. In addition, karyokinesis exponent is the sole independent predictor of progression-free survival of GISTs. The DNA, miRNA, and protein of exosomes have also been found to be biomarkers with prognostic implications. The research on the treatment of GISTs has become a focus in the era of precision medicine, ushering in the use of standardized, normalized, and individualized treatment.

Surgical Treatment of Gastric GIST: Feasibility of Laparoscopic Resection and Postoperative Outcome.

The aim of this study is to evaluate clinical manifestations and the possibility of laparoscopic treatment of large gastric stromal tumors. A case-series. Place and Duration of the Study: Ist Surgical Unit, Saint Spiridon Hospital Iasi and the Ist Oncological Surgical Unit, Regional Institute of Oncology Iasi, Romania, from May 2012 to May 2017. Patients with gastrointestinal stromal tumors (GISTs) who underwent surgery were selected. The clinical manifestations, type of surgical treatment, postoperative assessment of the risk factors, and follow-up for at least two years were analysed. Tumors longer than 5 cm were classified as large tumors. Forty-eight patients with GIST were seen, of which 25 (52.08%) had gastric tumor. Nine laparoscopic resections and 16 open interventions were performed on tumors up to 10 cm in size. The histopathological examination revealed 10 patients (40%) as class risk 3a / 3b. Complications were more frequent in open surgery, with an overall rate of 43.75% (7 patients) vs. 33.33% (3 patients) in laparoscopic surgery. Laparoscopic surgical procedures performed in experienced centres can also be applied to gastric tumors over 5 cm in well-selected cases without repercussions on survival. Key Words: Laparoscopy, Gastrointestinal stromal tumor, Gastric, Resection.

Endoscopic Submucosal Dissection of Gastrointestinal Stromal Tumours: A Retrospective Cohort Study.

BackgroundGastrointestinal stromal tumours (GISTs) are the most common mesenchymal neoplasms. Endoscopic submucosal dissection (ESD) has been used to remove submucosal tumours for many years. However, whether ESD can be recommended for the treatment of GISTs is still controversial. Therefore, we evaluated the efficacy and safety of ESD for treating GISTs.Patients and MethodsWe retrospectively analysed 75 GIST patients who underwent ESD in our hospital from January 2016 to December 2018, and the demographic data, clinical presentation of tumours, operative parameters, postoperative complications and length of hospital stay were analysed.ResultsSeventy-five patients successfully underwent en bloc resection, and 74 (98.7%) patients underwent complete resection of the lesions, with an average tumour size of 1.7 cm (range 0.3–6.0 cm). The median operation time was 84.8 min (range 20–180 min). Forty-two (56.0%) patients underwent endoscopic purse-string suture with no conversions to an open operation. The median postoperative length of hospitalization was 6.6 days (range 3–14 days). Out of a total of 75 GIST patients, 48 (64.0%) were considered very low risk, 19 (25.3%) were low risk, 5 (6.7%) were mild risk, and 3 (4.0%) were high risk. The median follow-up was 24.0 months (range 6–45 months). During hospitalization and follow-up, no complications, recurrence or metastasis occurred.ConclusionBased on our study from a medical centre, ESD is a safe and effective method for treating GISTs. However, further studies are needed.

Discovery and pharmacological characterization of AZD3229, a potent KIT/PDGFRα inhibitor for treatment of gastrointestinal stromal tumors.

Gastrointestinal stromal tumor (GIST) is the most common human sarcoma driven by mutations in KIT or platelet-derived growth factor α (PDGFRα). Although first-line treatment, imatinib, has revolutionized GIST treatment, drug resistance due to acquisition of secondary KIT/PDGFRα mutations develops in a majority of patients. Second- and third-line treatments, sunitinib and regorafenib, lack activity against a plethora of mutations in KIT/PDGFRα in GIST, with median time to disease progression of 4 to 6 months and inhibition of vascular endothelial growth factor receptor 2 (VEGFR2) causing high-grade hypertension. Patients with GIST have an unmet need for a well-tolerated drug that robustly inhibits a range of KIT/PDGFRα mutations. Here, we report the discovery and pharmacological characterization of AZD3229, a potent and selective small-molecule inhibitor of KIT and PDGFRα designed to inhibit a broad range of primary and imatinib-resistant secondary mutations seen in GIST. In engineered and GIST-derived cell lines, AZD3229 is 15 to 60 times more potent than imatinib in inhibiting KIT primary mutations and has low nanomolar activity against a wide spectrum of secondary mutations. AZD3229 causes durable inhibition of KIT signaling in patient-derived xenograft (PDX) models of GIST, leading to tumor regressions at doses that showed no changes in arterial blood pressure (BP) in rat telemetry studies. AZD3229 has a superior potency and selectivity profile to standard of care (SoC) agents-imatinib, sunitinib, and regorafenib, as well as investigational agents, avapritinib (BLU-285) and ripretinib (DCC-2618). AZD3229 has the potential to be a best-in-class inhibitor for clinically relevant KIT/PDGFRα mutations in GIST.

PCAT6 mediates cellular biological functions in gastrointestinal stromal tumor via upregulation of PRDX5 and activation of Wnt pathway.

Gastrointestinal stromal tumor (GIST) is a common mesenchymal tumor in the gastrointestinal tract. Prostate cancer associated transcript 6 (PCAT6) is a long noncoding RNA (lncRNA) and plays a pivotal role in tumor formation. Present study was designed to explore the function of PCAT6 in GIST. Ki67 staining, colony formation and trypan blue staining assays revealed that PCAT6 boosted GIST cell proliferation but inhibited cell apoptosis. Also, sphere formation assay and Western blot uncovered the promoting role of PCAT6 in GIST stemness. Then, we identified that PCAT6 could activate Wnt/β-catenin pathway. And the tumor facilitator role of Wnt/β-catenin pathway was validated in the rescue assays. Next, miR-143-3p was identified as the downstream microRNA of PCAT6. Moreover, miR-143-3p itself served as a tumor suppressor in GIST. Subsequently, peroxiredoxin 5 (PRDX5) was verified as the target of miR-143-3p. PCAT6 promoted GIST cell proliferation and stemness via sponging miR-143-3p to upregulate PRDX5. In a word, PCAT6 promoted GIST cell proliferation and stemness but inhibited cell apoptosis via competing endogenous RNA pattern and activation of Wnt pathway, which might contribute to GIST treatment.

The current status of and prospects in research regarding gastrointestinal stromal tumors in China.

China still lacks statistical data regarding the incidence of gastrointestinal stromal tumors (GISTs). Data from 3 regions have demonstrated that the incidence of GISTs in China is similar to that in the United States. Furthermore, no significant differences between both nations with regard to epidemiological characteristics and genotyping of GISTs have been reported. Chinese physicians are demonstrating an increased interest in studies regarding GISTs. Currently, to the authors' knowledge, China publishes the most research articles regarding GIST annually worldwide. Despite the paucity of relevant research regarding the clinical practices for GISTs, a series of studies performed by Chinese physicians in the fields of recurrence risk classification, laparoscopic surgery, and adjuvant therapy have contributed to the diagnosis and treatment of GISTs. The lack of innovative drugs, slow approval of new drugs, and insufficient research funds have limited further advancements in GIST-related research in China. In recent years, increased investment in scientific research has allowed for these advancements to be made by creating conditions for Chinese physicians to conduct high-level clinical research. Chinese researchers hope to further shorten the gap between China and the rest of the world in the field of GIST research within a relatively short period. The purpose of the current review article was to present the most updated information regarding the diagnosis and treatment of GISTs in Chinese medical practice and to suggest prospective research in this field.

Correlations between imatinib plasma trough concentration and adverse reactions in Chinese patients with gastrointestinal stromal tumors

Imatinib is the standard treatment for patients with gastrointestinal stromal tumors (GISTs), but there is significant variation in imatinib plasma trough concentrations (Cmin ) among patients. The imatinib Cmin distribution at different doses and the correlation of adverse reactions with Cmin in Chinese patients with GIST from a high-volume center were evaluated. From July 1, 2017 to December 31, 2018, patients who were receiving imatinib treatment for GIST were prospectively enrolled. Steady-state blood samples were obtained from patients who had received same-dose imatinib treatment for ≥1month with good compliance. Adverse reactions were recorded during regular follow-up, and blood samples were collected 24±2hours after dosing. Liquid chromatography-tandem mass spectrometry was used to measure drug concentrations. In total, 307 patients who received 367 dose levels were investigated. The imatinib Cmin was 1315±716ng/mL, 2117±597ng/mL, and 3844±987ng/mL in patients who were receiving imatinib 400mg, 600mg, and 800mg daily, respectively. The Cmin was significantly correlated with periorbital and limb edema (P<.001), anemia (P<.001), and rash (P=.037). Nausea and vomiting, diarrhea, and conjunctival hemorrhage also were correlated, but not significantly. A much higher Cmin was observed with severe adverse reactions. There was no correlation between the imatinib Cmin and leukopenia, muscle cramps, or hepatobiliary dysfunction. In Chinese patients with GIST, the imatinib Cmin was higher than that reported for Western populations, especially at higher doses. The Cmin was correlated with periorbital and limb edema, anemia, and rash, suggesting that monitoring the imatinib Cmin should be considered when patients develop severe adverse reactions caused by excessive imatinib plasma concentrations.

Diagnosis and Endoscopic Treatment of Gastrointestinal Stromal Tumors Arising from Esophagus.

Aim: The primary purpose of this study was to investigate the diagnosis and endoscopic treatment of gastrointestinal stromal tumors (GISTs) arising from esophagus. Materials and Methods: From January 2013 to December 2017, 16 cases of GISTs of esophagus were retrospectively identified from a total of >3000 GISTs treated in our center. Demographic characteristics, clinical data, endoscopic therapy outcomes, histopathology, and follow-up were analyzed. Results: The mean age of the patients was 53 years (range 35-71 years), mostly female (56.3%). Seven tumors were in the lower esophagus, five in the middle esophagus, and one in the upper esophagus. The most common symptom was abdominal discomfort (8/16; 50.0%), followed by acid reflux (6/16; 37.5%). All of the patients underwent CT scan, gastroscopy, and/or endoscopic ultrasound. Two patients were diagnosed with esophageal GISTs with a preoperative endoscopic biopsy. Tumors were resected completely in all patients by endoscopic surgery. The median operating time was 85 minutes (range 28-153 minutes), and the average tumor size was 11.6 mm (range 6-21 mm). Postoperative histopathology demonstrated esophageal GISTs were positive for CD117 and CD34. The mean length of postoperative hospital stay was 4.7 days (range 2-7 days). The median postoperative follow-up duration was 28 months (range 1-59 months). Conclusion: Endoscopic treatment seems to be safe and effective for tumors size <20 mm in diameter. However, long-term prospective randomized controlled trials are further needed.

Efficacy and Safety of Endoscopic Treatment for Gastrointestinal Stromal Tumors in the Upper Gastrointestinal Tract.

Background/Aims:Endoscopic treatment (ET) has been applied for decades to treat subepithelial tumors, including gastrointestinal stromal tumors (GISTs). However, the efficacy of ET remains debatable. In this study, we evaluated the efficacy and safety of ET for GISTs in the upper gastrointestinal tract. Methods:This retrospective single-center study included 97 patients who underwent ET. All patients were enrolled from July 2014 to July 2018. Parameters such as demographics, size, resection margin, complications, pathological features, procedure time, total cost, and follow-up were investigated and analyzed. Results:Our study achieved 100% en bloc resection and 77.4% (72/93) R0 resection. The most common location was the fundus with a mean tumor size of 2.1±1.4 cm. The mean age, procedure time, hospital stay, and cost were 59.7±11.3 years, 64.7±35.2 minutes, 6.8 days, and 5,337 dollars, respectively. According to National Institutes of Health classification, 63 (64.9%), 26 (26.8%), 5 (5.2%), and 3 (3.1%) patients belonged to the very low, low, intermediate, and high risk classification, respectively. Immunohistochemistry results showed a 100% positive rate of CD34, DOG-1, CD117, and Ki67. A mean follow-up of 21.3±13.0 months showed no recurrence or metastasis. Conclusions:ET is effective and safe for curative removal of GISTs in the upper gastrointestinal tract, and it can be a treatment of choice for patients with no metastasis.

Clinical outcomes of different therapeutic modalities for rectal gastrointestinal stromal tumor: Summary of 14-year clinical experience in a single center.

The optimal treatment for gastrointestinal stromal tumor (GIST) of the rectum is controversial due to the extremely low incidence of the disease. The aim of the present study was to compare the clinical outcomes of different treatment modalities for rectal GIST by reviewing the 14-year experience in our center. Medical records of rectal GIST patients who received surgical treatment in our center between January 2004 to December 2017 were reviewed retrospectively. Overall survival (OS) and recurrence-free survival (RFS) were used as the observation endpoints. Included in this study were 71 GIST patients, including 42 patients who underwent local excision (LE) and 29 patients who underwent segmental resection (SR). There were differences in tumor size (P=0.001) and malignant risk grade (P=0.007). The LE approach achieved a lower rate of R0 resection than SR (29/42 vs.27/29, P=0.015) and shorter hospital stay (P=0.004). Preoperative imatinib mesylate (IM) therapy improved the rate of sphincter-sparing surgery for patients with tumors in the very low segment of the rectum (P=0.012) and offered better R0 resection margins (P=0.027). Multivariate analysis showed that the resection margin status (P=0.014), risk stratification (P=0.001) and IM therapy (P=0.042) were independent factors affecting RFS of rectal GIST patients but not the surgical modalities (LE vs. SR, P=0.802). Multivariate analysis showed no significant impact of these variables on OS. Selection of surgical modalities has no significant impact on the prognosis. Local excision is the preferred surgical modality for resectable rectal GIST by virtue of less injury and shorter hospital stay. IM therapy has proved to be associated with improved RFS for rectal GIST patients.