Benign Gastrointestinal Stromal Tumors Research Articles

Submucosal tunneling endoscopic resection for rectal gastrointestinal stromal tumor.

A 60-year-old man was referred for evaluation of a rectal submucosal tumor located 5 cm proximal to the anus ([Video 1, ] [Fig. 1]). Endoscopic ultrasonography revealed a 3-cm hypoechoic lesion originating from the muscular layer. The patient underwent submucosal tunneling endoscopic resection (STER) under sedation with propofol for diagnosis and treatment ([Fig. 2]). A small horizontal incision was made at the anus and a submucosal pocket was created with injection of a mixture of hydroxyethyl starch and indigo carmine into the submucosal layer (GIF 190TH1; Olympus, Tokyo, Japan; and Flush Knife BTs 1.5 mm, FujiFilm, Tokyo, Japan). The tip of the tumor was enucleated ([Fig. 3]), and then the intramuscular portion of the tumor was dissected with a square-tip knife (Square Knife; Endoaccess, Garbsen, Germany) using spray coagulation (VIO 3; Erbe, Tübingen, Germany). Dissection was advanced up to the level of the perirectal fat, while paying attention to avoid damage to the tumor capsule. The tumor was removed en bloc ([Fig. 4]) and the mucosal entrance was closed with two clips. The procedure lasted for 1 hour. The patient was hospitalized for 1 night, received oral amoxicillin/clavulanic acid for 5 days, and had an uneventful recovery. Histology showed a benign gastrointestinal stromal tumor ([Fig. 4]). STER is mainly applied in the stomach and esophagus [1]. This case report demonstrates the feasibility of this technique in the rectum.

GIST: Correlation of risk classifications and outcome.

In clinical practice, there are often discrepancies between the oncological prognosis of gastrointestinal stromal tumors (GIST) and the actual clinical course. This study aimed to check with our collective how reliably the current classifications (Miettinen, Fletcher) predict the prognosis of GIST and to evaluate whether an extension of the classifications by the parameter proliferation activity could make sense. This prospective study enrolled 58 patients who underwent surgery on GIST from 01/2006 to 12/2016. The postoperative course (curation, recurrence, progress) was correlated with the identified risk classification and the proliferative activity. Coincidences with other tumors were strikingly common in patients with GIST (43%). Based on the risk group assignment of GIST, no assessment of the probability of the occurrence of second neoplasia could be derived. Individual patients were under- or over-graduated concerning the assessment of biological behavior based on the standard risk classifications. The inclusion of proliferative activity did not allow for a more precise predictive power - neither to the risk of recurrence and metastasis nor to the development of a second neoplasia. The study showed that there is currently no parameter or logarithm that reliably predicts the biological behavior of GIST. Due to the frequency of coincidence of second neoplasia and (rare) distant metastases, for everyday clinical practice, appropriate staging diagnostic and regular follow-up care should also be used for benign GIST.

Correlation between Three-Dimensional Volume and Malignant Potential of Gastrointestinal Stromal Tumors (GISTs).

Background and purpose: Gastrointestinal stromal tumors (GISTs) are rare diseases of the gastrointestinal tract but they are the most common gastrointestinal tumors of mesenchymal origin. Since most GISTs have malignant potential, their probability of malignant progression must be evaluated. This study was conducted to examine the correlation between three-dimensional GIST volume measured by CT and malignant potential. Materials and methods: A retrospective study was performed on 70 patients diagnosed with GIST after surgical resection in Hanyang University Seoul Hospital from 2012 to 2017. Linear regression analysis was used to establish which between the length of the long axis of GISTs, originally considered a predictor of malignancy, and their volume was a more accurate predictor of malignancy. Tumor dimensions were measured by CT. Results: Data were analyzed using the chi-square test or Student’s t-test and logistic regression. Of the GISTs, 53 (75.71%) were in the stomach, 3 (4.29%) in the small intestine, and 14 (20.0%) in the large intestine. The mean age of the malignant GIST group was significantly higher than that of the benign GIST group (p = 0.032), their tumor long axes were significantly greater (p = 0.073), their tumor volumes were significantly larger (p = 0.001), and the frequency of tumor necrosis was higher (p = 0.001). In multivariate analysis, malignant GIST was associated with location in organs other than the stomach (OR 7.846, 95% CI 1.293–47.624, p = 0.025), longer axis (OR 1.037, 95% CI 1.011–1.065, p = 0.006), larger volume (OR 1.003, 95% CI 1.000–1.006, p = 0.029), and necrosis (OR 12.222, 95% CI 1.945–76.794, p = 0.008). The mean age of the recurrent GIST group was higher than that of the non-recurrent group (p = 0.045), their tumor long axes were significantly longer (p = 0.005), and their volumes were greater, but this last difference was not significant (p = 0.072). Conclusions: Tumor volume can be considered an additional risk factor in assessing the malignant potential of GISTs and tends to increase in recurrent GISTs.

Surgical Management of GIST – A Single-Institutional Study

Background: Gastrointestinal stromal tumors (GIST) are quite rare tumors with estimated incidence of 1-1.5/100.000, often discovered incidentally during computed tomography or endoscopy. TNM classification has its limitations and it is not recommended in general. Benign GISTs do not exist and almost all GISTs should be considered as having some malignant potential. Prognostic factors include mitotic activity, tumor size, tumor site, considering also incomplete resection and intraoperative tumor rupture. Up to 94-98% of GIST are c-KIT protein positive (CD 117+), that is rarely expressed in other abdominal tumors. CD34 positivity is proved in 60-80% GISTs.

Ulcerated gastrointestinal stromal tumor causing a gastrogastric intussusception.

When a gastrointestinal intussusception is found, an underlying lesion should be excluded.

Expression profile of microRNAs in gastrointestinal stromal tumors revealed by high throughput quantitative RT-PCR microarray.

To investigate the microRNA (miRNA) expression profile in gastrointestinal stromal tumor (GIST) tissues that could serve as a novel diagnostic biomarker for GIST detection. We performed a quantitative real-time quantitative reverse transcriptase polymerase chain reaction assay to analyze the expression of 1888 miRNAs in a sample set that included 54 GIST tissue samples. We found that dysregulation of several miRNAs may be related to the malignant potential of GISTs. Six of these miRNAs, hsa-let-7c, miR-218, miR-488#, miR-4683, miR-34c-5p and miR-4773, were selected as the final list of biomarkers to separate the malignant GISTs (M group) from the benign GISTs (B group). In addition, MiR-29b-2#, hsa-let-7c, miR-891b, miR-218, miR-204, miR-204-3p, miR-628-5p, miR-744, miR-29c#, miR-625 and miR-196a were used to distinguish between the borderline (BO group) and M groups. There were 11 common miRNAs selected to separate the benign and borderline (BB) group from the M group, including hsa-let-7c, miR-218, miR-628-5p, miR-204-3p, miR-204, miR-891b, miR-488#, miR-145, miR-891a, miR-34c-5p and miR-196a. The identified miRNAs appear to be novel biomarkers to distinguish malignant from benign GISTs, which may be helpful to understand the mechanisms of GIST oncogenesis and progression, and to further elucidate the characteristics of GIST subtypes.

Surgical management of gastrointestinal stromal tumors: a single center experience.

IntroductionGastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal (GI) tract. Although the therapy targeted at inhibiting tyrosine kinases has shown dramatic results in metastatic and inoperable GISTs, the mainstay of treatment in primary localized forms remains surgical resection.AimTo provide an overview of our experience of GIST diagnosis and management, with emphasis on comparison of minimally invasive and open surgical resection for primary GISTs.Material and methodsWe retrospectively reviewed the medical records of all patients who underwent surgical removal of GISTs from 2008 to 2012. Patient demographics, clinical data, surgery, complications, histopathological data and clinical course were analyzed.ResultsForty-four patients were identified. Average age at diagnosis was 63 years. Minimally invasive (MIS) and open surgery (OS) were each attempted in 22 (50.0%) patients. Laparoscopic removal was performed in 20, laparoendoscopic in 1, and laparoscopy-assisted endoscopic removal in 1. Conversion to an open procedure was performed in 4 (18.2%). We found significant differences in postoperative length of stay (8.5 days vs. 10.1 days, p < 0.001) and tumor size (2.93 cm vs. 5.78 cm, p = 0.018) between MIS and OS groups, respectively.ConclusionsLaparoscopic removal is safe and effective for GISTs not exceeding 6 cm. Gastroesophageal junction and cardia GISTs require careful preoperative evaluation and planning to remove safely. We recommend avoiding laparoscopic removal of these tumors due to the high rate of conversion (100.0%) to an open procedure. Laparoendoscopic surgical approach is an appropriate technique for removal of small-sized intraluminal benign GISTs not involving the muscularis propria layer.

Synchronous gastric gastrointestinal stromal tumor and colon adenocarcinoma: a case report.

Gastrointestinal stromal tumors (GISTs) represent the majority of primary mesenchymal tumors of the gastrointestinal tract. They are generally considered to be solitary tumors and therefore the synchronous occurrence with other primary malignancies of gastrointestinal track is considered a rare event. Here we present the case of a 75-year-old man admitted to our hospital with a 10-day history of gastrointestinal bleeding. Colonoscopy revealed an ulcerative mass of 4 cm in diameter in the ascending colon. Gastroscopy revealed a bulge in the gastric body measuring 1 cm in diameter with normal overlying mucosa. Surgical intervention was suggested and ileohemicolectomy with regional lymph node resection along with gastric wedge resection was performed. Pathologic examination of the ascending colon mass showed an invasive moderately differentiated adenocarcinoma stage III B (T3N1M0). Grossly resected wedge of stomach showed a well circumscribed intramural tumor which microscopically was consistent with essentially benign gastrointestinal stromal tumor (according to Miettinen criteria). The patient did not receive additional treatment. Two years later the patient showed no evidence of recurrence or metastasis.

The relationship of clinical symptoms and pathological characteristics of 86 cases of gastrointestinal stromal tumor

Objective To explore the histogenesis,immunohistochemical and clinic pathological characteristics of gastrointestinal stromal tumor.Methods The postoperative pathological findings of 86 cases of gastrointestinal stromal tumor were analyzed retrospectively.Results The 86 cases of GIST were consisted of 10 benign cases,16 low-degree malignant cases and 60 high-degree malignant cases.53.5%(49/86) of which were from stomach,27.4%(23/86) from small intestine,4.7 %(4/86) from colon and 11.6%(10/86)from mesenteric.Innocuousness tumor group had no manifest bleeding and necrosis.Cells had no heteromorphism and less caryocinesia.Malignacy tumor group were abundance of cellulars and haemorrhage,necrosis,heteromorphism,caryocinesia were manifest.The positive rate of CD117(80 cases) was 93.0%,the positive rate of CD34(68 cases) was 79.1%,the positive of SMA( 13 cases) was 15.1% and the positive rate of S100(4 cases) was 4.7%.Conclusion Pathologic features are different between benign and malignant gastrointestinal stromal tumor,and it is necessary to use immunohistochemical marker for differentiation the diagnosis,particurly CD117 and CD34.There is strong relationship between the GIST malignancy and its size,mitomic index and anatomic location. Key words: Gastrointestinal stromal tumor(GIST); Immunohistochemistry; Pathology

Colorectal gastrointestinal stromal tumor

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm arising in the digestive tract, with an estimated prevalence of 15-20 per 1,000,000. GISTs are related to the interstitial cells of Cajal and are characterized by constitutive over-expression of the transmembrane tyrosine kinase receptor KIT. This is produced by a patognomonic mutation of the proto-oncogene c-kit that occurs in up to 90% of cases. Exon 11 is affected most frequently; exons 9 and 13 are less commonly involved. One-third of GISTs lacking KIT mutations exhibits alternative activating mutations in the PDGFRα gene. Colorectal GISTs represent about 5-10% of the cases, mainly located in the rectum that is the third common site. Benign GISTs are more common, but many tumors are of uncertain malignant potential; tumor size and rate of mitosis are still the most reliable criteria for assessing the risk of an aggressive behavior. Surgery is the first-line treatment for resectable non-metastatic colorectal GIST. Standard oncologic resection is inappropriate because skip metastases and lymphatic spread are rarely reported. Segmental colectomy with negative margins is recommended, and local excision is oncologically adequate in highly selected rectal tumors. Radical surgery alone is not always curative especially in high-risk GISTs, and half of patients develops local recurrences or distant metastases after R0 operation. Medical therapeutic strategies have rapidly evolved after the introduction of targeted molecular therapy. Efficacy and safety of imatinib mesylate was first demonstrated in patients with metastatic and unresectable disease. Adjuvant and neoadjuvant use of imatinib are promising therapeutic options to improve the outcome of surgery to downstage unresectable lesions and to allow less extensive resections.

Laparoendoscopic Single Site Partial Resection of the Stomach for Gastrointestinal Stromal Tumor

Laparoendoscopic single site surgery offers excellent cosmetic results and may be associated with decreased postoperative pain, reduced need for analgesia, and thus accelerated recovery. Preliminary experience with single-incision laparoscopic partial resection of the stomach for gastrointestinal stromal tumor (GIST) is reported. A single curved intraumbilical 25-mm incision was made with pulling out the umbilicus, and a 12-mm and two 5-mm ports were inserted. The submucosal gastric tumor located in the anterior wall of the stomach was resected with 2 endoscopic staplers under the retraction of 2-mm mini-loop retractor. The procedure was completed successfully without any perioperative complications, and there was no need to extend the skin incision. The operative time was 64 minutes. The final pathologic diagnosis was benign GIST. Postoperative follow-up did not reveal any umbilical wound complication. Laparoendoscopic single site partial resection of the stomach for GIST is feasible and a promising alternative method for scarless abdominal surgery.

Uterine Tumor Resembling an Ovarian Sex Cord Tumor Associated With Metastasis

Uterine tumors resembling ovarian sex-cord tumors (UTROSCT) are very rare, usually benign uterine tumors, and are probably derived from uterine mesenchymal stem cells. In this case report, a unique case of a malignant UTROSCT is described. Four years after a diagnosis of UTROSCT of the uterine corpus, the patient developed obstructive ileus due to a large infiltrating tumor within the small bowel with the same morphology and expression pattern as the previously diagnosed UTROSCT. In addition, 2 benign gastrointestinal stromal tumors were detected in the same patient. This case indicates that although the majority of UTROSCT are benign tumors, some of them might undergo malignant transformation and have a metastatic potency.

Gastrointestinal stromal tumors: Usefulness of immunohistochemistry, flow cytometry and fluorescence in situ hybridization

Gastrointestinal stromal tumors (GIST) constitute a group of primary mesenchymal tumors of the gastrointestinal tract, known for their diversity in clinical behavior and the difficulties in determining malignancy and prognosis. This retrospective study evaluated a series of GIST by means of immunohistochemical techniques, flow cytometry and fluorescence in situ hybridization (FISH). Nine patients with GIST were analyzed for tumor size, mitotic count and CD117, CD34, MIB-1 with immunohistochemistry. In addition, the GIST were tested with FISH for chromosomes 8 and 17 and DNA index was evaluated by flow cytometry. The findings confirmed the usefulness of CD117 and CD34 in diagnosing GIST and the prognostic role of MIB-1, but do not support a correlation between aneuploidy in flow cytometry and poor outcome. The FISH results suggest close follow-up for patients with benign GIST with a numerical alteration of chromosome 8. The technique could select patients with tumors at high-risk with aneusomy of chromosome 17. This study shows the possible application of FISH to the evaluation of patients with GIST, in addition to analysis of morphological features.

Pediatric Jejunal Gastrointestinal Stromal Tumor Diagnosed by Wireless Capsule Endoscopy

Pediatric Jejunal Gastrointestinal Stromal Tumor Diagnosed by Wireless Capsule Endoscopy

CT diagnosis of gastrointestinal stromal tumors

目的 分析胃肠道间质瘤(GIST)的CT表现特点,探讨CT对该肿瘤的诊断价值.方法 回顾性分析经手术病理证实的GIST16例,术前均行CT平扫和增强扫描.结果 肿物发生部位胃7处,小肠12处,结肠3处.16例CIST中良性4例,肿瘤直径≤5.0 cm,边界清楚,密度均匀;恶性12例,肿瘤直径≥7cm,肿瘤边缘有分叶,肿块内有坏死,肿瘤的溃疡大而深,可见周围组织侵犯或远处转移.结论 CT对GIST具有较高的诊断价值,可弥补其他影像学检查的局限性,对临床早期诊断和治疗以及评价预后具有重要价值。

Clinicopathological and immunohistochemical analysis of gastrointestinal stromal tumor

To investigate the clinicopathological features of gastrointestinal stromal tumor (GIST) and to study the reference indexes for malignancy. Fifty-two cases of primary GIST were distinguished from a group of gastrointestinal mesenchymal tumors using a panel of antibodies such as CD117 and CD34 by immunohistochemical SP method. Their biological behaviors were analyzed using the expression of p21WAF1 and Bax in 52 cases of GIST. Grossly, the tumor size was between 1.5 cm and 13 cm (mean: 5.5 cm). Focal areas of hemorrhage, necrosis, or small cyst formation could be seen. Microscopically, the tumor was composed of spindle cells (20 cases), epithelioid cells (20 cases) and mixed cells (12 cases). Immunohistochemically, CD117 and CD34 showed diffuse strong positive expressions, the positive rates were 98.1% and 92.3%. SMA, S-100, NSE, NF and MBP showed focal positive expressions, the positive rates were 48.1%, 28.8%, 25%, 21.2% and 42.3% respectively. Vimentins were all positive desmin and CgA were all negative. In normal adult stomach and intestine, the immunoreactive staining for CD117 and CD34 showed immunoreactive interstitial cells of Cajal in myenteric neuroplexus. Among the 52 cases of GIST, 27 were positive for p21WAF1 (51.9%), 29 for Bax (55.8%). The expression of p21WAF1 and Bax had no significent difference with the localization, size, histological subtype of GIST, but had a significent difference with the histological grade (P = 0.000, respectively). p21WAF1 expression had a positive correlation to Bax expression (r = 0.461, P = 0.001, kappa = 0.459). GIST has complicated arrangements and various cell types. Positivity of CD117 and CD34 is the most valuable factor in diagnosing GIST. Expression of p21WAF1 and Bax plays an important role in potential malignancy and malignancy rather than in benign GIST. p21WAF1 and Bax may be used as the markers in the assessment of GIST malignant potential.

The GIST of a stromal tumor

The GIST of a stromal tumor

Estimation of the malignant potential of gastrointestinal stromal tumors: the value of contrast-enhanced coded phase-inversion harmonics US

Recently, contrast agents for ultrasonography (US) such as Levovist have been introduced for routine clinical use. The contrast-enhanced US with Levovist permits evaluation of the intratumoral vascularity of hepatic and pancreatic tumors and is useful for their differential diagnosis. The purpose of the present study was to assess tumor vessels and the parenchymal flow of gastrointestinal stromal tumors (GISTs) by contrast-enhanced coded phase-inversion harmonic US and to evaluate whether vascularity is related to the malignant grade of the GISTs. Thirteen patients with GISTs were included in the present study. Tumors were observed in a real-time fashion of contrast-enhanced coded phase-inversion harmonic US after the injection of Levovist (400 mg/ml). The vascular patterns were compared with tumor size, histological diagnosis, KIT mutations, and clinical findings such as metastasis. The contrast-enhanced US images of the GISTs were classified into two types according to the blood flow area of the tumors as seen by real-time continuous imaging of the tumor vessels. The image pattern "Poor" represented vessels flowing only in the peripheral part of the tumor, and "Rich" represented abundant vessels flowing from the periphery to the central part of the tumor. According to the contrast-enhanced US images, five GISTs were classified as "Poor" and the others as "Rich." Based on the final diagnosis, all tumors with "Poor" images were determined to be benign GISTs, and the rest tumors except one with "Rich" images were determined to be malignant GISTs. Contrast-enhanced US image is more closely correlated with the final diagnosis than the histological findings.

Analysis of the value of CT and EUS in diagnosing gastrointestinal stromal tumors

目的 探讨胃肠道间质瘤的CT和超声内镜诊断价值.方法搜集经手术和病理证实的胃肠道间质瘤患者11例进行回顾性分析.11例均行螺旋CT平扫,10例行双期增强扫描,8例行超声内镜检查.结果肿瘤位于胃部8例,食管、十二指肠和直肠各1例.本组良性者,肿瘤直径≤5 cm,边界清楚,密度均匀,可见单个坏死灶.恶性者,有如下特征:(1)肿块直径≥7 cm;(2)肿瘤边缘有分叶;(3)瘤体内有多个小片状坏死或大块坏死;(4)肿瘤的溃疡大而深;(5)瘤旁常伴成簇状或线状排列的小血管;(6)瘤体内有散在分布的细小钙化点;(7)周围组织侵犯或远处转移.本组CT定位准确度为54.5%(6/11),超声内镜定位准确度为87.5%(7/8).病理学检查肿瘤为良性者3例,恶性者7例,增生活跃者1例.CT判定良恶性准确度为72.7%(8/11),超声内镜判定良恶性准确度为62.5%(5/8).结论 CT和超声内镜结合有助于胃肠道间质瘤的定位和良恶性的判断,对指导临床治疗和估计预后有一定的价值。

C-kit gene mutation in human gastrointestinal stromal tumors.

To investigate the significance of c-kit gene mutation in gastrointestinal stromal tumors (GIST). Fifty two cases of GIST and 28 cases of other tumors were examined. DNA samples were extracted from paraffin sections and fresh blocks. Exons 11, 9 and 13 of the c-kit gene were amplified by PCR and sequenced. Mutations of exon 11 were found in 14 of 25 malignant GISTs (56%), mutations of exon 11 of the c-kit gene were revealed in 2 of 19 borderline GISTs (10.5%), and no mutation was found in benign tumors. The mutation rate showed significant difference (chi2=14.39, P<0.01) between malignant and benign GISTs. Most of mutations consisted of the in-frame deletion or replication from 3 to 48 bp in heterozygous and homozygous fashions, None of the mutations disrupted the downstream reading frame of the gene. Point mutations and frame deletions were most frequently observed at codons 550-560, but duplications were most concentrated at codons 570-585. No mutations of exons 9 and 13 were revealed in GISTs, Neither c-kit gene expression nor gene mutations were found in 3 leiomyomas, 8 leiomyosarcomas, 2 schwannomas, 2 malignant peripheral nerve sheath tumors, 2 intra-abdominal fibromatoses, 2 malignant fibrous histiocytomas and 9 adenocarcinomas. C-kit gene mutations occur preferentially in malignant GISTs and might be a clinically useful adjunct marker in the evaluation of GISTs and can help to differentiate GISTs from other mesenchymal tumors of gastrointestinal tract, such as smooth muscle tumors, schwannomas, etc.