Small Intestinal Gastrointestinal Stromal Tumors Research Articles

Characteristics and predictors of outcomes with neoadjuvant imatinib in gastrointestinal stromal tumors: Real-world data from a large patient registry.

737 Background: The standard of care for patients with moderate or high-risk resectable gastrointestinal stromal tumors (GIST) is surgical resection followed by adjuvant therapy with imatinib. The impact of neoadjuvant imatinib on long-term outcomes is largely unknown. Methods: We interrogated the LifeRaft registry, a large international open cohort of patients with GIST. We included patients who did not have metastatic disease at diagnosis, underwent surgical resection and received neoadjuvant imatinib and had no recorded mutations of Kit exon 13 or PDGFRA exon 18 D842V. Baseline patient characteristics were described and survival probabilities were estimated and plotted using the Kaplan-Meier method. Cox regression was used to estimate the effect of demographic and clinical characteristics on recurrence-free survival (RFS) and overall survival (OS). For RFS, time was calculated from the date of surgery to disease recurrence/death, whichever came first. For OS, time was calculated from the date of surgery to death. Estimated effects of predictors were reported as hazard ratios (HR) along with 95% confidence intervals (CI). All statistical testing was two-sided and assessed for significance at the 5% level using SAS v9.4 (SAS Institute, Cary, NC). Results: Out 2,472 patients with GIST, 137 patients met the inclusion criteria and received neoadjuvant imatinib for a median of 6.8 months. Majority of the patients were aged 40 years or above (129/137, 94.2%) and were males (73/137, 53.3%). The majority of the patients had gastric GIST (72/137, 54.1%), followed by small intestine GIST (34/137, 25.6%) and other (27/137, 20.3%). Most patients had a tumor size of >10 cm (66/137, 52.4%) at the time of diagnosis followed by >5 cm - <=10 cm (42/137, 33.3%) and >2 cm - <=5 cm (18/137, 14.3%). The median RFS for the cohort was 6.1 years. On multivariable analysis, tumor size (HR 1.08, 95% CI 1.05-1.12, p<0.01) and the overall duration of treatment (neoadjuvant and adjuvant) with imatinib therapy (HR 0.98, 95% CI 0.97-0.99, p<0.01) were significantly associated with RFS. A 1-cm increase in tumor size and 1-month increase in total time on imatinib was associated with an 8% increase and 2% decrease in risk of recurrence. The median OS was 14.2 years. Female gender (HR 0.23 95% CI 0.08-0.65, p<0.01) and total length of time on imatinib (HR 0.97 95% CI 0.96-0.99, p<0.01) were found to be significantly associated with OS. Female patients were associated with a 77% decreased risk of death and a 1-month increase in the total time on imatinib was associated with a 3% decrease in the risk of death. Conclusions: We show that most patients receiving neoadjuvant imatinib have gastric GIST with tumor size >10 cm. Smaller tumor size and female gender predicted longer RFS and OS respectively. Longer total duration of imatinib therapy was associated with increased RFS and OS.

NTRK2 expression in gastrointestinal stromal tumors with a special emphasis on the clinicopathological and prognostic impacts

Gastrointestinal stromal tumors (GISTs) are typically characterized by activating mutations of the KIT proto-oncogene receptor tyrosine kinase (KIT) or platelet-derived growth factor receptor alpha (PDGFRA). Recently, the neurotrophic tyrosine receptor kinase (NTRK) fusion was reported in a small subset of wild-type GIST. We examined trk IHC and NTRK gene expressions in GIST. Pan-trk immunohistochemistry (IHC) was positive in 25 (all 16 duodenal and 9 out of 16 small intestinal GISTs) of 139 cases, and all pan-trk positive cases showed diffuse and strong expression of c-kit. Interestingly, all of these cases showed only trkB but not trkA/trkC expression. Cap analysis of gene expression (CAGE) analysis identified increased number of genes whose promoters were activated in pan-trk/trkB positive GISTs. Imbalanced expression of NTRK2, which suggests the presence of NTRK2 fusion, was not observed in any of trkB positive GISTs, despite higher mRNA expression. TrkB expression was found in duodenal GISTs and more than half of small intestinal GISTs, and this subset of cases showed poor prognosis. However, there was not clear difference in clinical outcomes according to the trkB expression status in small intestinal GISTs. These findings may provide a possible hypothesis for trkB overexpression contributing to the tumorigenesis and aggressive clinical outcome in GISTs of duodenal origin.

Effect of tumor location on the efficacy of chemotherapy for gastrointestinal stromal tumors.

790 Background: Gastrointestinal stromal tumors (GISTs) arise from multiple sites within the gastrointestinal tract. Since the introduction of imatinib in 2002, patients have seen improved overall survival. However, a recent National Cancer Database (NCDB) study suggested no survival benefit to adjuvant imatinib for colorectal GIST patients. Another recent study showed that small bowel GISTs have larger median tumor size and higher incidence of tumors with at least 5 mitoses compared to gastric GISTs. These findings suggest a differential tumor biology for GISTs arising from different primary tumor sites, potentially conferring differential response to imatinib. In this NCDB study, we compare overall survival outcomes with and without chemotherapy, stratifying by primary tumor site. Methods: We queried the NCDB from 2004-2018 for patients with GIST histology. We excluded patients with age <40, age>80, high comorbidity score, and patients who received additional therapy other than surgery or chemotherapy. Of the 22,846 patients meeting criteria for our study, 27 patients had tumors originating from the anus, 454 from the colon, 173 from the esophagus, 15,296 from the stomach, 556 from the rectum, 32 from the rectosigmoid junction, and 6,308 from the small intestine. 8,983 (39%) received chemotherapy. Treatment with chemotherapy was used to extrapolate response to imatinib, the mainstay of treatment. Results: Cox proportional hazards analysis demonstrated increased hazard of death for chemotherapy, increasing age, and comorbidity score of 1. Positive predictive factors for survival included female sex and later year of diagnosis. For anal, esophageal, gastric, and rectosigmoid GIST patients, there was no statistically significant overall survival benefit for any treatment modality. For colonic GISTs, neoadjuvant chemotherapy combined with surgery improved overall survival. For rectal GISTs, adjuvant chemotherapy with surgery also provided survival benefit. For small intestinal GISTs, surgery alone or surgery with neoadjuvant, adjuvant, or both neoadjuvant and adjuvant chemotherapy improved overall survival. Conclusions: While our study is retrospective and limited as a NCDB study, our Kaplan-Meier survival analysis demonstrated survival benefit for chemotherapy only in patients with colon, rectal, or small intestinal GIST tumors. Our Cox proportional analysis demonstrated an overall negative survival impact for chemotherapy. These findings lend further support to the idea that differential tumor biology at each primary site may lead to differential response to imatinib. Overall, our study provides rationale for further investigating the heterogeneity of GIST tumor microenvironments, as these differences could contribute to the differential treatment outcomes.

The analysis of prognostic factors of primary small intestinal gastrointestinal stromal tumors with R0 resection: A single-center retrospective study.

Objective:We aim to assess factors that affect overall survival in patients with primary small intestinal gastrointestinal stromal tumors (GISTs) who had undergone R0 resection.Method:A retrospective analysis reviewed the data of 82 consecutive confirmed GIST patients at a single medical center in China from January 2012 to June 2020. The survival curve was estimated using the Kaplan–Meier method, and independent prognostic factors were confirmed using the Cox regression model.Results:A total of 82 patients were included in the study: 42 men and 40 women, the mean age was 59 years old (23–83 years old). Tumors were commonly found in the jejunum (46.3%), ileum (20.7%), and duodenum (32.9%). The median tumor size was 6.0 cm (range: 1.0–15.0 cm). The number of mitoses per one 50 high-power field was used to define the mitotic rates. In our present study, 56 patients presented a mitotic rate ≤5 (68.3%) and 26 patients showed a rate >5 (31.7%) at the time of diagnosis. All patients accepted tumor resection without lymph node resection. The positivity rate was 97.6% for CD117, 96.3% for delay of germination 1, 65.9% for CD34, 6.1% for S-100, and 59.8% for smooth muscle actin using immunohistochemistry. Tumor size, tumor rupture, Ki67 index, mitotic index, and postoperative imatinib were independent prognostic factors for small intestinal GISTs.Conclusions:In this study, larger tumor size, high Ki67 index, high mitotic index, the occurrence of tumor rupture, and use of imatinib were independent unfavorable prognostic indicators.

Fourth-line rescue treatment ripretinib of advanced small intestine gastrointestinal stromal tumors who achieved partial response: a case report

With the advances in gastrointestinal stromal tumors (GISTs) research and the development of new immunotherapy drugs, the emergence of targeted drugs has greatly changed the diagnosis and treatment of GISTs and benefited more GIST patients. However, drug resistance has become increasingly challenging with the widespread application of targeted therapy in GIST patients. Based on the currently available evidence, the United States Food and Drug Administration (US FDA) has approved sunitinib as a second-line therapy and regorafenib as a third-line therapy, and research and development of more molecularly-targeted drugs are underway. A middle-aged male patient was diagnosed with advanced small intestine GIST. Following the resection (R2) of tumors in the small intestine and pelvis, the patient received first-, second-, and third-line adjuvant therapies. However, follow-up examinations indicated progressive disease (PD). Ripretinib was then administered as the fourth-line therapy, and partial response (PR) was achieved 6 months later. To the best of our knowledge, this is a rare case in which the fourth-line adjuvant therapy for GIST achieved significant efficacy after unsuccessful systematic first-, second-, and third-line therapies. Imatinib, as the first-choice targeted therapy for advanced GISTs, has achieved notable clinical efficacy. After localized tumor progression on imatinib, second-line sunitinib may be applied. Third-line regorafenib therapy can be used in patients with GISTs who have failed both imatinib and sunitinib. In our current case, the patient experienced PD after regorafenib administration, and a satisfactory efficacy was obtained following the use of ripretinib. For patients with GISTs, after the failure of imatinib, sunitinib, and regorafenib, ripretinib may achieve a good therapeutic effect as a new targeted drug. Ripretinib is currently approved for use as a fourth-line or higher therapy in advanced GISTs, However, the ultimate place of ripretinib in metastatic or advanced GIST remains under investigation. This case achieved the therapeutic effect of PR through the treatment of repatinib, and there were no other obvious side effects except hair loss. Our findings may inform clinical decision-making regarding the treatment of GISTs. Gastrointestinal stromal tumor (GIST); imatinib; ripretinib; case report.

Case report: successful treatment of a rare large jejunal gastrointestinal stromal tumour with surgery and using principle of short-term fasting

Small intestinal gastrointestinal stromal tumours (GISTs) are rare mesenchymal tumours of gastrointestinal tract comprise 0.04% of small intestinal neoplasms. We presented a case of 61 years female presenting in emergency with pain in epigastrium, multiple episodes of vomiting, raised total leucocyte counts. CECT abdomen showed a large non-enhancing jejunal lesion. The patient had emergency small bowel resection and anastomosis. Postoperative patient started on imatinib and kept on short-term fasting. This case report highlights the rare presentation of jejunal GISTs, successful surgical outcome and good enhancing effect of short-term fasting on chemotherapy.

Gastric and small intestine gastrointestinal stromal tumors: our experience

Background: Gastrointestinal stromal tumors (GIST) are rare, although their incidence has increased in recent years. They are characterized by presenting a mutation in the c-Kit gene (CD117). The most common location is the stomach, followed by the small intestine and less frequently in the large intestine, esophagus, and mesentery. The main prognostic factors are the mitotic index and tumor size, and the main treatment is surgical resection. The spread is mainly hepatic and peritoneal. The objective of this study is to present our departments’ experience in the surgical treatment and long-term outcomes of GIST tumors in the stomach and small intestine.

CADM1 promotes adhesion to vascular endothelial cells and transendothelial migration in cultured GIST cells.

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the human gastrointestinal tract. Small intestinal GISTs appear to be associated with poorer prognosis and higher metastasis rate than gastric GISTs of the same size and mitotic index. Recently, we reported that cell adhesion molecule 1 (CADM1) is expressed specifically in most small intestinal GISTs, but not in most gastric GISTs, suggesting that this difference in CADM1 expression between gastric GISTs and small intestinal GISTs might influence the difference in clinical behavior between them. The aim of the present study was to examine whether high CADM1 expression affected proliferation, migration, invasion, adhesion to endothelial cells and transendothelial migration of cultured GIST cells by comparing original GIST-T1 cells with very low CADM1 expression with GIST-T1 cells with high CADM1 expression induced by CADM1 cDNA transfection (GIST-T1-CAD cells). GIST-T1-CAD cells had reduced ability to proliferate, migrate and invade compared with the original GIST-T1 cells, but showed significantly higher ability to adhere to human umbilical vein endothelial cells and migrate through endothelial cell monolayers. Thus, CADM1 may contribute to higher metastasis rates in small intestinal GISTs facilitating tumor cell adhesion to vascular endothelial cell and transendothelial migration of tumor cells. CADM1 might serve as a potential target for inhibition of metastasis in small intestinal GISTs.

Histomorphological Spectrum and Immunohistochemical Features of Gastrointestinal Stromal Tumour: A Series of Eight Cases

Gastrointestinal Stromal Tumours (GISTs) are rare tumours of the Gastrointestinal Tract (GIT), consisting of <1% of all primary GIT neoplasms. Recent studies show an increased incidence, which may be due to improved diagnostic facilities. In contrast to the literature’s judgement and the findings of many Western research, which state that the stomach is the most common place, it was observed that the small intestine was more common. Consequently, the goal of this case series was to characterise the clinicopathological, histomorphological, and immunohistochemical spectrum of GISTs as well as their risk categorisation in accordance with the modified Miettinen and Lasota’s algorithm. Eight patients with GISTs diagnosed between January 2017 and December 2020 at tertiary care centre of Gujarat, India are presented in this case series. There was one young woman among the patients, others were middle or old age male or female and had a median age of 58.5 years. The most typical presentation was abdominal pain, albeit in one instance it was an unexpected discovery. One example of extra Extra GISTs (EGIST), where there were several retro and intraperitoneal masses, and one small intestinal GIST each had lymphoma as the tentative clinical diagnosis. Predominant spindle cell morphology was observed in contrast to other studies. Even if molecular studies are not available in resource-limited countries, the basic Immunohistochemistry (IHC) panel is the most useful in the final diagnosis. Risk stratification criteria are helpful for prognostication and further management with the use of appropriate targeted therapies.

The prognostic significance of pleomorphism in gastrointestinal stromal tumours.

Gastrointestinal stromal tumours (GISTs) typically show uniform nuclear morphology, with spindle cell, epithelioid or mixed histology. Risk of progression in GIST is estimated based on anatomical site, tumour size and mitotic index. Pleomorphic GISTs are rare and have not been systematically investigated. We evaluated the prognostic significance of pleomorphism in GIST. In total, 108 of 2517 (4.3%) GISTs reviewed between 2000 and 2021 were reported to show pleomorphism. Seventeen cases underwent mutational testing. Pleomorphism was noted prior to therapy in 37 GISTs, affecting 18 males and 19 females, with a mean age of 55.4 years. Most tumours arose in the stomach (n = 15) or small intestine (n = 19), with a mean size of 9.2 cm and a median mitotic rate of seven per 5 mm2 ; the median follow-up was 5.7 years. Immunohistochemistry for KIT was positive in 36 (97.3%) tumours. Mutational testing revealed KIT and PDGFRA mutations in 68.4 and 21.0% of cases, respectively; no SDHX, KIT or PDGFRA alterations were found in two cases (one of which was succinate dehydrogenase-deficient). According to standard risk assessment criteria for progressive disease, 18 tumours were high-risk, five were moderate-risk, four were low-risk, five were very low-risk and one had no risk. Disease progression was exclusive to high-risk tumours (79%; P < 0.001). Pleomorphism is present prior to therapy in approximately 2% of GISTs and is most prevalent in high-risk gastric and small intestinal GISTs. Pleomorphism appears to have no prognostic significance beyond conventional risk stratification.

Differential Expression of CADM1 in Gastrointestinal Stromal Tumors of Different Sites and with Different Gene Abnormalities.

Gastrointestinal stromal tumor (GIST), the most common mesenchymal tumor of the human gastrointestinal tract, differentiating toward the interstitial cell of Cajal (ICC), arises predominantly in the stomach and small intestine. Small intestinal GISTs appear to have worse prognosis than gastric GISTs. In a pilot study of a cDNA expression chip using several GISTs, we found that Cell Adhesion Molecule 1 (CADM1), which could contribute to tumor growth and infiltration, is expressed more strongly in small intestinal GISTs than gastric GISTs. In the present study, we examined CADM1 expression in GISTs of different sites and with different gene abnormalities using a large number of gastric and small intestinal GISTs. First, immunoblotting confirmed significantly higher CADM1 expression in small intestinal GISTs with exon 11 c-kit mutation than gastric GISTs with exon 11 c-kit mutation. Real-time PCR also revealed that small intestinal GISTs with exon 11 c-kit mutation showed significantly higher CADM1 mRNA than gastric GISTs with exon 11 c-kit mutation. Although most small intestinal GISTs showed high CADM1 mRNA expression regardless of gene abnormality types, different CADM1 expression was detected between gastric GISTs with c-kit mutation and those with PDGFRA mutation. Immunohistochemistry showed that many small intestinal GISTs were CADM1-positive but most gastric GISTs CADM1-negative or -indefinite. In the normal gastric and small intestinal walls, immunoreactivity of CADM1 was detected only in nerves, but neither in gastric ICCs nor small intestinal ICCs, indicating that the high CADM1expression in small intestinal GISTs might be acquired during tumorigenesis. Different CADM1 expression between gastric and small intestinal GISTs might be related to different prognoses between them. Further functional experiments are needed to elucidate the role of CADM1 on GIST biology, and there is a possibility that targeting therapy against CADM1 has a preventive effect for tumor spreading in small intestinal GISTs.

Gastric and Small Intestine Gist: Results of 156 Cases in 20 Years.

Gastric and small intestine are the most common gastrointestinal stromal tumors (GISTs). There are few studies of patients who underwent surgical treatment with disparate findings. We aimed to evaluate the differences between groups and the risk factors for recurrence and mortality. A retrospective study of 96 gastric and 60 small intestine GIST was performed between 1995 and 2015. Both groups were compared in terms of clinicopathologic features, morbidity, recurrence, and mortality. Statistical analysis was performed with SPSS®. Eighty-one gastric GISTs and 56 small intestine GISTs underwent surgical treatment. Gastrointestinal bleeding was the most common cause of emergency surgery being more frequent in gastric GIST (P = 0.009); however, emergency surgery was indicated more frequently in the small intestinal GIST (P = 0.004) and was mostly due to perforation (P = 0.009). With a median follow-up of 66.9 (39.7-94.8) months, 28 (20.4%) patients had recurrence. A mitotic index > 5 (P ≤ 0.001) and the intestinal location (P = 0.012) were significantly associated to recurrence. Tumor size > 15cm (P = 0.001) and an age of ≥ 75years (P = 0.014) were associated to mortality. On univariate analysis, higher mean values of Ki-67 were associated to higher mortality (P = 0.0032). Small intestine GIST presented lower disease-free survival (DFS) than that of gastric GIST (65.7% vs 90.8%) with P = 0.003. The overall survival (OS) of gastric and small intestine GIST was 74.7% and 71.6%, respectively (P = 0.68). Small intestine GIST received emergency surgery more frequently showing lower DFS and same OS than that of gastric GIST. We found that Ki-67 could be a prognostic factor. Further studies are necessary to assess whether Ki-67 is a prognostic risk factor for GISTs.

Building contrast-enhanced CT-based models for preoperatively predicting malignant potential and Ki67 expression of small intestine gastrointestinal stromal tumors (GISTs).

To assess contrast-enhanced computed tomography (CE-CT) features for predicting malignant potential and Ki67 in small intestinal gastrointestinal stromal tumors (GISTs) and the correlation between them. We retrospectively analyzed the pathological and imaging data for 123 patients (55 male/68 female, mean age: 57.2years) with a histopathological diagnosis of small intestine GISTs who received CE-CT followed by curative surgery from May 2009 to August 2019. According to postoperatively pathological and immunohistochemical results, patients were categorized by malignant potential and the Ki67 index, respectively. CT features were analyzed to be associated with malignant potential or the Ki67 index using univariate analysis, logistic regression and receiver operating curve analysis. Then, we explored the correlation between the Ki67 index and malignant potential by using the Spearman rank correlation. Based on univariate and multivariate analysis, a predictive model of malignant potential of small intestine GISTs, consisting of tumor size (p < 0.001) and presence of necrosis (p = 0.033), was developed with the area under the receiver operating curve (AUC) of 0.965 (95% CI, 0.915-0.990; p < 0.001), with 91.53% sensitivity, 96.87% specificity, 96.43% PPV, 92.54% NPV, 94.31% diagnostic accuracy. For high Ki67 expression, a model made up of tumor size (p = 0.051), presence of ulceration (p = 0.054) and metastasis (p = 0.001) may be the best predictive combination with an AUC of 0.785 (95% CI, 0.702-0.854; p < 0.001), 63.33% sensitivity, 76.34% specificity, 46.34% PPV, 86.59% NPV, 73.17% diagnostic accuracy. Ki67 index showed a moderate positive correlation with mitotic count (r = 0.578, p < 0.001), a weak positive correlation with tumor size (r = 0.339, p < 0.001) and with risk stratification (r = 0.364, p < 0.001). Features on CE-CT could preoperatively predict malignant potential and high Ki67 expression of small intestine GISTs, and Ki67 index may be a promising prognostic factor in predicting the prognosis of small intestine GISTs, independent of the risk stratification system.

Establishment and Verification of a Nomogram for Predicting Survival in Patients with Small Intestinal Gastrointestinal Stromal Tumors

Background: This study aimed to develop and validate nomograms for predicting overall survival (OS) and cancer-specific survival (CSS) in small intestinal gastrointestinal stromal tumors (SI GISTs). Methods: Patients diagnosed with SI GISTs were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database and further randomly divided into training and validating cohorts. Univariate and multivariate Cox analyses were conducted in the training set to determine independent prognostic factors to build nomograms for predicting 3- and 5-year OS and CSS. The performance of the nomograms was assessed by using the concordance index (C-index), calibration plot, and the area under the receiver operating characteristic curve (AUC). Results: Data of a total of 776 patients with SI GISTs were retrospectively collected from the SEER database. The OS nomogram was constructed based on age, surgery, imatinib treatment, and American Joint Committee for Cancer (AJCC) stage, while the CSS nomogram incorporated age, surgery, tumor grade, and AJCC stage. In the training set, the C-index for the OS nomogram was 0.773 (95% confidence interval [95% CI]: 0.722–0.824) and for the CSS nomogram 0.806 (95% CI: 0.757–0.855). In the internal validation cohort, the C-index for the OS nomogram was 0.741, while for the CSS nomogram, it was 0.819. Well-corresponded calibration plots both in OS and CSS nomogram models were noticed. The comparisons of AUC values showed that the established nomograms exhibited superior discrimination power than the 7th Tumor-Node-Metastasis staging system. Conclusion: Our nomogram can effectively predict 3- and 5-year OS and CSS in patients with SI GISTs, and its use can help improve the accuracy of personalized survival prediction and facilitate to provide constructive therapeutic suggestions.

Outcomes of gastric and small Intestinal GISTs (Gastrointestinal Stromal Tumors) after curative resection and aggressive re-resection of recurrence; in Imatinib era: A propensity matched analysis.

Background: Surgical resection remains the mainstay of treatment for localized GISTs. Prognostication and need for adjuvant imatinib are based on risk stratification which includes tumor site as an important factor with small intestine lesions having poor prognosis as compared to gastric primary. Aim of this study is to evaluate oncological outcomes of gastric and small intestinal GIST patients undergoing curative resection, focusing on the role of primary tumor site as a prognostic indicator.

HAND1 and BARX1 Act as Transcriptional and Anatomic Determinants of Malignancy in Gastrointestinal Stromal Tumor

Gastrointestinal stromal tumor (GIST) arises from interstitial cells of Cajal (ICC) or their precursors, which are present throughout the gastrointestinal tract. Although gastric GIST is commonly indolent and small intestine GIST more aggressive, a molecular understanding of disease behavior would inform therapy decisions in GIST. Although a core transcription factor (TF) network is conserved across GIST, accessory TFs HAND1 and BARX1 are expressed in a disease state-specific pattern. Here, we characterize two divergent transcriptional programs maintained by HAND1 and BARX1, and evaluate their association with clinical outcomes. We evaluated RNA sequencing and TF chromatin immunoprecipitation with sequencing in GIST samples and cultured cells for transcriptional programs associated with HAND1 and BARX1. Multiplexed tissue-based cyclic immunofluorescence and IHC evaluated tissue- and cell-level expression of TFs and their association with clinical factors. We show that HAND1 is expressed in aggressive GIST, modulating KIT and core TF expression and supporting proliferative cellular programs. In contrast, BARX1 is expressed in indolent and micro-GISTs. HAND1 and BARX1 expression were superior predictors of relapse-free survival, as compared with standard risk stratification, and they predict progression-free survival on imatinib. Reflecting the developmental origins of accessory TF programs, HAND1 was expressed solely in small intestine ICCs, whereas BARX1 expression was restricted to gastric ICCs. Our results define anatomic and transcriptional determinants of GIST and molecular origins of clinical phenotypes. Assessment of HAND1 and BARX1 expression in GIST may provide prognostic information and improve clinical decisions on the administration of adjuvant therapy.

A Case of Small Intestinal Gastrointestinal Stromal Tumor That Required Emergency Surgery After Preoperative Diagnosis of Intra-abdominal Abscess

A Case of Small Intestinal Gastrointestinal Stromal Tumor That Required Emergency Surgery After Preoperative Diagnosis of Intra-abdominal Abscess

A Thirteen and a Half Year Survival Case of Small Intestine Gastrointestinal Stromal Tumor with Multiple Liver Metastases Treated with Combined Therapies Including Radiofrequency Ablation

A Thirteen and a Half Year Survival Case of Small Intestine Gastrointestinal Stromal Tumor with Multiple Liver Metastases Treated with Combined Therapies Including Radiofrequency Ablation

A Case of Small Intestinal Gastrointestinal Stromal Tumor That was Difficult to Distinguish from an Ovarian Tumor: A Case Report

術前に卵巣腫瘍と鑑別が困難であった小腸Gastrointestinal stromal tumor（GIST）の手術症例を経験したので報告する．症例は67歳の女性．健診にて貧血を指摘され，近医で上下部消化管内視鏡検査を施行するも，異常所見なく，婦人科疾患の精査目的に当院産婦人科を紹介受診となった．骨盤部造影CT検査にて右卵巣に一致して内部造影不良域を伴う長径51mmの境界明瞭な腫瘤を認め，骨盤部造影MRI検査では子宮右側に53×38×48mm大の内部非造影領域と辺縁造影効果を伴う腫瘤を認めた．右卵巣腫瘍の診断で開腹子宮全摘，両側付属器切除術の予定となったが，開腹所見にて腫瘍は子宮や両側付属器と連続しておらず，小腸原発腫瘍と判明したため，術中に当科紹介となった．腫瘍の肉眼所見は壁外発育性のGIST様で小腸リンパ節の明らかな腫大を認めなかったため，小腸部分切除術を施行した．手術時間は１時間54分，出血は少量であった．術後経過は良好で術後第７病日に軽快退院となった．骨盤内に落ち込んだ小腸原発性腫瘍と卵巣腫瘍などの婦人科系腫瘍性疾患は鑑別が難しく，今回術前卵巣腫瘍と鑑別困難であった小腸GISTの手術症例を経験したため，文献的考察を交えて報告する．

Small intestine gastrointestinal stromal tumor and malignant peripheral nerve sheath tumor in a patient with neurofibromatosis type 1: A case report

AbstractThe clinical manifestation of neurofibromatosis type 1 (NF1) predisposes patients to the development of a variety of neoplasms, such as neurofibroma, malignant peripheral nerve sheath tumors (MPNSTs), optic pathway glioma, gastrointestinal stromal tumors (GISTs), and pheochromocytoma. We report the case of a patient with NF1 who underwent surgery for MPNST of the right upper abdominal wall in which a GIST arising in the jejunum was found incidentally. Two years later, the patient underwent surgical resection of a GIST in the small intestine owing to clinical manifestation of gastrointestinal hemorrhage. Further imaging examination is required for symptomatic plexiform neurofibroma to distinguish between an MPNST and other benign subcutaneous tumors. Patients with NF1 should undergo periodic computed tomography image surveillance because they are of increased risk of developing GISTs. Standard therapy for NF1‐GIST is surgery, and patients should be carefully followed up after tumor resection.