Identification of gastrointestinal stromal tumors from leiomyomas in the esophagogastric junction: A single-center review of 136 cases.

To identify significant clinical and CT features for the differentiation of gastrointestinal stromal tumors (GISTs) from leiomyomas in the esophagogastric junction (EGJ).One hundred thirty six patients with pathologically proven GISTs (n = 87) and leiomyomas (n = 49) in the EGJ were enrolled. And preoperative CT images were available in 73 GISTs cases and 34 leiomyoma cases. Two radiologists reviewed the CT images by consensus with regard to tumor size, shape, growth pattern, surface, enhancement pattern, enhancement degree, attention at each phasic image and the presence of surface ulcer, calcification, and intralesional low attention.Eight significant clinical and CT features were identified for differentiating GISTs from leiomyomas: older age (>46.5 years), tumor long diameter >4.5 cm, heterogeneous enhancement, high degree enhancement, mean CT attenuation >69.2 HU, presences of intralesional low attenuation and surface ulcer, absences of calcification (P < .05). On the receiver operating characteristic curve analysis, an optimal cutoff score of 3.5 was achieved for differentiating GISTs from leiomyomas with an AUC of 0.844 (sensitivity: 76.7%, specificity: 76.5%).older age (>46.5 years), tumor long diameter >4.5 cm, heterogeneous enhancement, high degree enhancement, mean CT attenuation >69.2 HU, presences of intralesional low attenuation and surface ulcer, absence of calcification are significant features highly suggestive of GISTs in differentiation from leiomyomas in the EGJ.

The epithelioid gastrointestinal stromal tumor with pulmonary metastasis: A rare case report and literature review.

RATIONALE: Available literature states that the histological subtype of the gastrointestinal stromal tumor (GIST) with pulmonary metastasis is often spindle cell type. To our knowledge, this is the first report of the GIST with pulmonary metastasis of very uncommon epithelioid subtype. PATIENT CONCERNS: We report a 63-year-old male presenting with the symptom of bloodstained sputum without obvious inducement. The patient had no chest pain, low back pain, fatigue, fever or night sweats symptoms. DIAGNOSES: Combined chest digital radiography and the history of the patient who presented with the colon GIST of the epithelioid subtype two years ago that the mass may be a metastasis tumor. Combined with morphological and immunohistochemical staining results, a pathological diagnosis of the GIST with pulmonary metastasis was considered. INTERVENTIONS: Right lobectomy and partial upper lobectomy were performed. OUTCOMES: The patient had not experienced any noticeable symptom and recurrent tumors at 6 months follow-up. LESSONS: We report a rare case of the GIST with pulmonary metastasis of epithelioid subtype. This case is of great significance to the pathologist's clinical work. For pathologists, if an epithelioid tumor in the lung is found, it is necessary to check whether the gastrointestinal tract also has the tumor, which may be an epithelioid GIST with pulmonary metastasis.

Laparoscopic resection of intestinal stromal tumors with transrectal extract specimen: A case report.

RATIONALE: Small intestine stromal tumors (SISTs) are a type of gastrointestinal stromal tumor (GIST) that has an insidious onset. Natural orifice specimen extraction (NOSE) surgery has been gradually developed for the treatment of colorectal, stomach, small intestine, hepatobiliary, and gynecological tumors because of its safety and feasibility. This case study explored the possibility of applying the NOSE method for the treatment of SIST. PATIENT CONCERNS: A 59-year-old male patient was admitted to the hospital after having an irregular abdominal mass for >1 month that was detected by a medical examination. Thoracic and abdominopelvic enhanced computer tomography revealed irregular masses on the left side of the abdominal cavity. DIAGNOSIS: Sist. INTERVENTIONS: Nose (laparoscopic resection of intestinal stromal tumors with transrectal extract specimen and no abdominal auxiliary incision) surgery was performed. OUTCOMES: The patient underwent operation successfully and recuperates well with no complications. LESSONS: Nose surgery is minimally invasive, results in patient recuperation with no complications, and is considered to be feasible for SIST treatment.

Biochemical Inhibition of DOG1/TMEM16A Achieves Antitumoral Effects in Human Gastrointestinal Stromal Tumor Cells In Vitro.

BACKGROUND/AIM: DOG1 is a calcium-activated chloride channel that has gained attention as a promising drug target due to its involvement in several processes essential for tumor development and progression. DOG1 is overexpressed in >95% of gastrointestinal stromal tumors (GIST). The aim was to determine DOG1 inhibition antitumoral effects on GIST. MATERIALS AND METHODS: Human GIST (GIST-T1 and GIST882) cell lines were used to study the effect of DOG1 inhibitors on chloride currents, viability, colony formation, and cell cycle. RESULTS: CaCCinh-A01 decreased chloride currents. CaCCinh-A01 and T16inh-A01 reduced GIST cell viability and CaCCinh-A01 affected cell cycle distribution leading to G1 cell-cycle arrest. CaCCinh-A01 also increased the sub-G1 phase population, indicative of apoptosis, in GIST882. CaCCinh-A01 strongly reduced the colony forming ability of the cells, whereas T16inh-A01 did not. CONCLUSION: DOG1 inhibition has antitumoral effects in GIST cells in vitro, and could potentially serve as a target for GIST therapy.

Gastrointestinal Stromal Tumor in a Patient with Neurofibromatosis Type 1 That Was Successfully Treated with Regorafenib.

An unconscious 55-year-old man with a history of neurofibromatosis type 1 (NF1) was transported to the emergency department and was diagnosed with acute renal failure owing to a large bladder tumor. A submucosal tumor was also identified in the duodenum. The patient was diagnosed with a primary gastrointestinal stromal tumor (GIST) of the bladder and duodenum. After six cycles of regorafenib therapy, 18F-fluorodeoxyglucose accumulation in the duodenal GIST on positron emission tomography-computed tomography (PET-CT) showed a partial metabolic response. Currently, no standard drug therapy for unresectable or relapsed NF1-associated GIST has been established. Regorafenib may thus be considered as and appropriate initial therapy.

Gallbladder GIST: A review of literature.

Mesenchymal tumors of the gallbladder are rarely encountered in clinical practice. The Gastrointestinal Stromal Tumor (GIST) of the gallbladder is rarely encountered. These tumors most commonly arise from the interstitial cells of Cajal (ICC), the pacemakers of the intestinal system. There can be benign as well as malignant forms of GIST. The literature on GIST arising from the gallbladder wall is limited to a few case reports only. In extensive search of the indexed literature, only 9 cases of gallbladder GIST were retrieved. Based on the available literature these tumors are commonly found in females. They usually present with hypochondrial pain with or without other features of cholangitis. These tumors are usually malignant and warrant a radical surgical excision. The data on postoperative adjuvant therapy and survival is limited. The authors presented a review of the available literature on this rare pathology.

SCF-KIT signaling induces endothelin-3 synthesis and secretion: Thereby activates and regulates endothelin-B-receptor for generating temporally- and spatially-precise nitric oxide to modulate SCF- and or KIT-expressing cell functions.

We demonstrate that SCF-KIT signaling induces synthesis and secretion of endothelin-3 (ET3) in human umbilical vein endothelial cells and melanoma cells in vitro, gastrointestinal stromal tumors, human sun-exposed skin, and myenteric plexus of human colon post-fasting in vivo. This is the first report of a physiological mechanism of ET3 induction. Integrating our finding with supporting data from literature leads us to discover a previously unreported pathway of nitric oxide (NO) generation derived from physiological endothelial NO synthase (eNOS) or neuronal NOS (nNOS) activation (referred to as the KIT-ET3-NO pathway). It involves: (1) SCF-expressing cells communicate with neighboring KIT-expressing cells directly or indirectly (cleaved soluble SCF). (2) SCF-KIT signaling induces timely local ET3 synthesis and secretion. (3) ET3 binds to ETBR on both sides of intercellular space. (4) ET3-binding-initiated-ETBR activation increases cytosolic Ca2+, activates cell-specific eNOS or nNOS. (5) Temporally- and spatially-precise NO generation. NO diffuses into neighboring cells, thus acts in both SCF- and KIT-expressing cells. (6) NO modulates diverse cell-specific functions by NO/cGMP pathway, controlling transcriptional factors, or other mechanisms. We demonstrate the critical physiological role of the KIT-ET3-NO pathway in fulfilling high demand (exceeding basal level) of endothelium-dependent NO generation for coping with atherosclerosis, pregnancy, and aging. The KIT-ET3-NO pathway most likely also play critical roles in other cell functions that involve dual requirement of SCF-KIT signaling and NO. New strategies (e.g. enhancing the KIT-ET3-NO pathway) to harness the benefit of endogenous eNOS and nNOS activation and precise NO generation for correcting pathophysiology and restoring functions warrant investigation.

Giant oesophageal gastrointestinal stromal tumour presenting with dyspnoea and clubbed fingers.

Gastrointestinal stromal tumours (GISTs) are mesenchymal neoplasms of the gastrointestinal tract originating from the interstitial cells of Cajal. Giant oesophageal GISTs are rare since the oesophagus is rarely the primary site of GISTs, and they are usually diagnosed early due to complaints such as dysphagia. We present the case of a giant oesophageal GIST presenting with prominent clubbing. The case underlined the diagnostic importance of clubbing and the careful consideration of chemotherapy. Although clubbed fingers associated with GISTs are rare, our experience demonstrates the importance of physicians' recognition of clubbing as a paraneoplastic phenomenon for early diagnosis of malignancies since patients seldom notice their own clubbing by themselves. Chemotherapy using imatinib, an Bcr-Abl kinase inhibitor, is the standard option for unresectable giant GISTs. However, careful consideration must be made of the risk of complications associated with rapid mass reduction due to imatinib such as bleeding, oesophageal perforation and mediastinitis.

Utilidad de la neoadyuvancia en el manejo del GIST rectal / Utility of neoadjuvant therapy in rectal GIST

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Diagnosis and treatment of gastrointestinal stromal tumor extending to prostate: A case report and literature review.

RATIONALE: Gastrointestinal stromal tumor (GIST) is the neoplasm of gastrointestinal tract. PATIENT CONCERNS: The patient complained about the retention of urinary. DIAGNOSES: GIST. INTERVENTIONS: radical prostatectomy and the imatinib therapy. OUTCOMES: No recurrence and metastasis have been found during a 14-month follow-up. LESSONS: comprehensive treatment is necessary for the GIST treatment. Furthermore, we summarize a review of the literature of GIST occurring in the prostate gland treated by different methods and 4 kinds of rare diseases in prostate.

Prevalence, Impact, and Correlates of Severe Fatigue in Patients With Gastrointestinal Stromal Tumors.

CONTEXT: The introduction of the tyrosine kinase inhibitor (TKI) imatinib in the treatment of gastrointestinal stromal tumor (GIST) in 2000 was the start of a new era of targeted treatment. Since then, the median survival of patients with GIST has substantially increased. Prolonged survival and chronic TKI use are associated with treatment-induced symptoms, such as fatigue, which can compromise quality of life (QoL). OBJECTIVES: This study determined the prevalence of severe fatigue in GIST patients compared to matched healthy controls, the impact of fatigue on daily life, and associations between fatigue and current TKI use. METHODS: One hundred nineteen patients treated with surgery and/or a TKI for GIST were asked to participate. Participants completed questionnaires including the Checklist Individual Strength-Fatigue Severity scale (CIS-fatigue), Short-Form 36-Item Health Survey, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30, Fatigue Catastrophizing Scale, Self-Efficacy Scale, and the Hospital Anxiety and Depression Scale. RESULTS: Eighty-nine GIST patients (75%) completed questionnaires, 61 patients (69%) were on a TKI. Prevalence of severe fatigue measured with CIS-fatigue was significantly higher in GIST patients (30%) than in 234 matched healthy controls (15%). The prevalence of severe fatigue did not differ significantly between patients receiving treatment with curative (29%) or palliative intent (36%). Severely fatigued patients reported lower QoL and more impairment on all functional domains. TKI use, more psychological distress, and lower physical functioning were associated with fatigue. CONCLUSION: Severe fatigue occurs in 30% of GIST patients and in 33% of GIST patients on a TKI. The fatigue is disabling and is not only associated with current TKI use but also with psychological distress and physical functioning. GIST patients should be informed about these associated factors of fatigue that deserve appropriate management.

Metachronous Primary Adenocarcinoma of Lung During Adjuvant Imatinib Mesylate Therapy for Gastrointestinal Stromal Tumor of Stomach: A Case Report.

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor in gastrointestinal tracts; however, the synchronous or metachronous coexistence of GIST with additional primary malignancy is not common.Here, we present an unusual case of gastric GIST with metachronous primary lung adenocarcinoma diagnosed during his adjuvant treatment with oral receptor tyrosine kinase inhibitor imatinib mesylate (400 mg daily). After 6-month use of imatinib, the patient suffered from dry cough and dyspnea. Subsequent lung biopsy demonstrated adenocarcinoma with diffuse interstitial changes.Our research emphasizes the possibility of an additional primary tumor with GIST, and reminds the clinicians to strengthen the surveillance of the additional cancer during the follow-up of GIST patients.

Gastrointestinal stromal tumour with unusual sites of metastasis: accurate staging with 18F-FDG PET/CT / Tumor del estroma gastrointestinal con metástasis en localización poco habitual: una estadificación correcta con 18F-FDG PET/TC

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Oncogenic KIT-containing exosomes increase gastrointestinal stromal tumor cell invasion.

During tumor development, constant interplay occurs between tumor cells and surrounding stromal cells. We report evidence that gastrointestinal stromal tumor (GIST) cells invade the interstitial stroma through the release of the oncogenic protein tyrosine kinase (KIT)-containing exosomes, which triggers the phenotypic conversion of progenitor smooth muscle cells to tumor-promoting cells. These recipient cells display morphologic changes and acquire tumor-associated phenotypes, including enhanced adhesion to extracellular matrix proteins, activation of intracellular pathways downstream of KIT, expression of Interstitial Cell of Cajal-like markers, and release of various matrix metalloproteinases (MMPs), particularly MMP1. This report shows stimulation of MMP1 production by stromal cells via uptake of tumor-derived exosomes, which leads to tumor cell invasion. Exosomes derived from GIST patients but not healthy donors show enhanced MMP1 secretion by smooth muscle cells and tumor cell invasion, whereas selective blocking of exosome-mediated MMP1 secretion decreases tumor invasiveness. Our study indicates that exosome release and subsequent MMP1 induction creates a positive feedback mechanism established between tumor and stromal cells that drives GIST development and offers unique insights for potential therapeutic strategies to block GIST progression and metastatic spread.

[A case of imatinib-resistant gastrointestinal stromal tumor treated with low-dose sunitinib].

The patient was an 82-year-old man who had undergone resection of a gastrointestinal stromal tumor(GIST)of the small intestine in January 2000, when he was 69 years old. As peritoneal recurrences were diagnosed in June 2002, we performed peritoneal tumorectomy twice, and the perirectal tumor was controlled with imatinib for over 7 years. Resistance to imatinib was diagnosed in March 2011, and treatment was switched to sunitinib. Administration of sunitinib was started at 50mg/day for 28 days followed by treatment withdrawal for 14 days; however, the dose needed to be reduced twice and then discontinued owing to the occurrence of side effects and pemphigoid. During discontinuation of sunitinib, the tumor increased in size and cancer pain appeared; therefore, sunitinib was re-administered at a very low-dose of 12.5mg every alternate day. Low dose sunitinib was effective; the perirectal tumor was reduced and cancer pain disappeared.

Tyrosine kinase inhibitors induced thyroid dysfunction: a review of its incidence, pathophysiology, clinical relevance, and treatment.

Tyrosine kinase inhibitors (TKI) belong to a new class of molecular multitargeted anticancer therapy which targets different growth factor receptors and hence attenuates cancer cell survival and growth. Since their introduction as adjunct treatment for renal cell carcinoma and gastrointestinal stromal tumors (GIST), a number of reports have demonstrated that TKI can induce thyroid dysfunction which was especially more common with sunitinib maleate. Many mechanisms with respect to this adverse effect of tyrosine kinase inhibitors have been proposed including their induction of thyroiditis, capillary regression in the thyroid gland, antithyroid peroxidase antibody production, and their ability to decrease iodine uptake by the thyroid gland. Of interest is the observation that TKI-induced thyroid dysfunction may actually be protective as it was shown to improve overall survival, and it was suggested that it may have a prognostic value. Followup on thyroid function tests while patients are maintained on tyrosine kinase inhibitor is strongly recommended. When thyroid dysfunction occurs, appropriate treatment should be individualized depending on patients symptoms and thyroid stimulating hormone level.