Correlation between MRI features and tumor risk grade in gastrointestinal stromal tumors / 中国肿瘤临床

To investigate the correlation between magnetic resonance imaging (MRI) features and tumor risk grade of gas-trointestinal stromal tumors (GISTs). Methods: Between September 2007 to December 2017, 54 patients who underwent MRI and were pathologically diagnosed in Tianjin Medical University Cancer Institute and Hospital were retrospectively reviewed. We analyzed MRI features including the size, location, shape, boundary, and growth pattern of the tumor; cystic necrosis; metastasis; T1WI and T2WI signal intensities; enhancement signal intensity-time (SIT) curve pattern; and average apparent diffusion coefficient (ADC) val-ues. The MRI features were compared with the tumor risk grade. Results: Of the 54 cases, 16 were of low-risk grade, 13 were of inter-mediate-risk grade, and 25 were of high-risk grade. Statistical analysis showed that tumor size, location, shape, boundary, cystic necro-sis, signal intensity, and average ADC values were correlated with tumor risk grade (P<0.05). However, tumor growth pattern, metasta-sis, and enhancement SIT curve pattern were not correlated with tumor risk grade (P>0.05). GISTs with higher aggressive features were more likely to have larger size, irregular shape, unclear boundary, cystic necrosis, heterogeneous signal intensity, and lower ADC values on MRI. Conclusions: MRI has the potential to predict the risk grade of GISTs before surgery, thereby guiding clinical manage-ment, and evaluating prognosis.

Gastrointestinal stromal tumors (GISTs): single center experience observed in a small series of cases / Tumores del estroma gastrointestinal (GISTs): experiencia de un centro único en una serie de casos

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms developing in the stomach. Usually detected incidentally, they can be single or multiple. The aim of this study is to report the results of surgery in the treatment of GISTs in terms of postoperative morbidity (POM) and recurrence. Case series. Patients surgically treated by GISTs at the Clínica Mayor of Temuco, Chile, between 2008 and 2015 were included. The preoperative study consisted in general diagnostic tests, endoscopy and abdominal CT-Scan. The outcome variable was POM, measured at 30 days postoperatively. Other variables of interest were: surgical time, hospital stay, mortality and recurrence. Minimum follow-up time was 12 months. Descriptive statistics were used. Four patients with GISTs were operated in the study period. Median age was 67 years, and 50 % of the patients were female. The median time of symptoms was 6 months. Excision of the lesion was performed in all cases with a median surgical time of 129 min. POM was 25 % (one case developed a seroma of the surgical wound), grade I of Clavien & Dindo proposal. Hospital stay was 4 day in all cases and no operative mortality was reported. With a median follow-up of 24 months there was not evidenced of recurrence. Although the results were positive, it is worth mentioning that this was a very small number of cases, therefore, they should be considered with caution.

Los tumores del estroma gastrointestinal (GISTs), son las neoplasias del mesénquima más comunes del estómago. Su detección es usualmente incidental; y pueden ser únicas o múltiples. El objetivo de este estudio, es reportar los resultados de la cirugía en el tratamiento de los GISTs en términos de morbilidad postoperatoria (MPO) y recurrencia. Serie de casos retrospectiva. Se incluyeron los pacientes intervenidos quirúrgicamente por GISTs en la Clínica Mayor de Temuco, Chile, entre los años 2008 y 2015. El estudio preoperatorio consistió en pruebas diagnósticas generales, endoscopia y tomografía computarizada abdominal. La variable resultado fue MPO medida a los 30 días del postoperatorio. Otras variables de interés fueron: tiempo quirúrgico y de hospitalización, mortalidad y recurrencia. El tiempo de seguimiento mínimo considerado fue 12 meses. Se utilizó estadística descriptiva. En el período en estudio, se operaron 4 pacientes con GISTs. La mediana de edad fue 67 años y el 50 % de los casos era de sexo femenino. La mediana del tiempo de síntomas fue 6 meses. La exéresis de las lesiones se realizó en todos los casos, con una mediana de tiempo quirúrgico de 129 min. La MPO fue 25 % (un paciente desarrolló un seroma de la herida quirúrgica), grado I de Clavien & Dindo. La estadía hospitalaria fue de 4 días en todos los casos. No hubo mortalidad; y con una mediana de seguimiento de 24 meses, no se ha evidenciado recurrencia. Si bien los resultados son buenos en todas las variables observadas, es fundamental señalar que se trata de un pequeño número de casos; por ende, deben considerarse con precaución.

The 10 Years of Experiences with GISTs

PURPOSE: Gastrointestinal stromal tumors (GISTs) possess highly variable clinical behaviors and the study thereof is insufficient. There are no standard guidelines for diagnosis and treatment of GISTs, so it is difficult to predict recurrences and conduct appropriate treatments. Throughout the last 10 years of experiences with GIST patients, we have identified the variables predicting recurrences and classified the risk groups by NIH classification, Fletcher risk stratification and UICC TNM stage. METHODS: From January 1998 to December 2007, 88 patients with pathologic confirm and surgical resection were diagnosed with GISTs. GISTs were diagnosed when the tumor had characteristic histologic features and confirmed positive by KIT, CD34, or PDGFRA. RESULTS: The size, mitotic index, existence of symptoms, and origins of tumor correlate statistically with recurrence (0.002, <0.001, 0.027, 0.011). The NIH classification, Fletcher risk stratification and UICC TNM stage are correlated with recurrence (0.001, <0.001, <0.001) and 5 year disease free survival, statistically (0.009, <0.001, <0.001). Fifteen patients experienced recurrences. 14 patients were treated with imatinib, and 6 of them showed a response to the treatment. All 4 patients who had R1 resection did not survived due to the progression of the disease. CONCLUSION: The patients with large, high mitotic index, symptomatic, or extra-gastric tumor require strict surveillance. Also, patients with low risk must be under surveillance due to the possibility of recurrence. It is important to perform R0, en bloc resection. Although the imatinib is the treatment of choice with recurred or metastatic GISTs, the disease is likely to develop resistance, further studies on newly targeted therapy is in need.

Clinicopathologic Analysis of Gastrointestinal Stromal Tumors of the Colon and Rectum

PURPOSE: This study's aim is to investigate the clinicopathologic characteristics of colorectal gastrointestinal stromal tumors (GISTs) and to evaluate the result of those tumors. METHODS: We retrospectively reviewed 22 patients who had been diagnosed with primary colorectal GISTs and who had undergone a surgical resection between October 1996 and July 2008. RESULTS: Colorectal GISTs accounted for 0.28% of all colorectal malignancies and 7.7% of all GISTs. Rectal GISTs (19, 86.4%) were more common than colonic GISTs (3, 13.6%). According to the National Institute of Health's (NIH) grading system, there were 1 (4.5%) very low, 5 (22.7%) low, 4 (18.2%) intermediate, and 12 (54.6%) high-risk tumors. The disease recurred in 7 patients (1 with intermediate risk and 6 with high risk). Recurrence sites were the liver (42.9%), the peritoneum (71.5%), and the lymph nodes (14.3%). Adjuvant imatinib therapy and/or radiation therapy were done for patients with microscopically positive margins of resection and high risk, of which one experienced a recurrence at 95 months after surgery. The five-year recurrence rates were 0% in the very-low-grade and low-grade groups, 33.3% in the intermediate-grade group, and 37.5% in the high-grade group. The five-year overall survival rates were 100% in the very-low-grade and low-grade groups, 66.7% in the intermediate-grade group, and 62.5% in the high-grade group. CONCLUSION: Poor prognosis of colorectal GISTs was closely related to the tumor's histologic grade and size. Integrating surgery, molecular therapy, and radiation therapy might improve outcomes, but further study with more cases is needed.

Laparoscopic Wedge Resection of GISTs Involving the Second Portion of the Duodenum

The optimal surgical procedure for treatment of gastrointestinal stromal tumors (GISTs) of the duodenum remains undefined. Therefore, various surgical procedures have been introduced as treatment options for duodenal GISTs. Due to the anatomical complexity, the laparoscopic approach has been considered as a contraindication. Especially for GISTs located at the second portion of the duodenum, a laparoscopic wedge resection is technically difficult to perform. We describe the surgical technique of laparoscopic wedge resection with hand-sewn closure for GISTs that involve the second portion of the duodenum.

cKIT mutations in GISTs and other malignancies in Thailand.

Objective: 1) To further identify tumors other than GISTs; 2) To study cKIT gene mutation for proper Imatinib treatment. Methods: Fresh tumor tissue samples were obtained from: 2 tissue samples of GISTs; 1 parotid cancer; 1 soft tissue sarcoma; 1 chondrosarcoma; 1 liposarcoma and 1 pure seminoma. The fresh tissues were divided into two portions: one for histopathological diagnosis and cKIT protein study, the other for DNA extraction and cKIT gene mutation study. Results: The authors described the gastrointestinal stromal tumors (GISTs) and other malignancies associated with positive cKIT protein in Thailand. We also describe briefly the methodology and molecular techniques used in the study of the mutation of cKIT gene in our laboratory using DNA sequencing method. Examples of positive cKIT protein and deletion mutation as well as missense (point mutation) mutations from our own patients are shown. Mutation study of exons 9, 11, 13 and 17 of cKIT gene in all 7 patients was carefully done to assist us in treating those patients with Imatinib therapy. Conclusion: Mutation study of cKIT gene could be done routinely in our molecular laboratory in Thailand. We recommend cKIT gene mutation study be done in every case of GIST and tumor with positive cKIT protein other than GIST prior to initiation of Imatinib therapy.

Clinical Analysis of Recurrent Gastrointestinal Stromal Tumor (GIST) Patients

PURPOSE: Gastrointestinal stromal tumors (GISTs) are of a mesenchymal origin, and they arise predominantly from the gastrointestinal tract. This study aims to aid the post operative management of GIST patients by analyzing the clinical and immunopathological features of recurrent GISTs. METHODS: We enrolled 98 GIST patients who had been operated on for their primary tumor from 1987 to 2001 at the Catholic Medical Center. Among them, 28 patients had clinical and radiological features that were proved to be recurrence, and the patients' survival rates were compared according to the treatment modalities. RESULTS: When the maximum length of tumor was shorter and the mitotic index lower, then these patients had higher disease free survival rates and lower recurrence rates. The Ki-67 negative group had lower recurrence rates than their Ki-67 positive counterparts. Recurrence was mostly observed as liver metastasis. The mean length of time to recur was 22.96 months. Fifteen patients received additional treatments such as surgery, chemotherapy and radiation therapy, but there was no significant difference in survival rates when they were compared to the 13 patients who did not receive further treatments. CONCLUSION: Of the patients diagnosed with GIST after surgery, those with worse prognostic factors, i.e. a bigger tumor size and higher mitotic index, require more meticulous surveillance for tumor recurrence, and especially for liver recurrence, which was the most common recurrence site, during the follow up exams. In addition, although there have not been any remarkably effective treatments for the recurrent GIST patients, further researches for new therapy such as STI-571 is mandated.

A Case of Gastrointestinal Stromal Tumor in a Child / 대한소아소화기영양학회지

Gastrointestinal stromal tumors (GISTs) are the most common primary mesenchymal tumors of the digestive tract. They have been commonly observed in adults but have been rarely described in children. They arise typically from the intestinal wall and rarely in the mesentery, omentum, or retroperitoneum. GISTs originate from the interstitial cell of Cajal and are characterized by overexpression of the receptor tyrosine kinase c-kit. Up to 94% of these tumors express the CD117 on immunohistochemical stain. Surgery is the main modality of treatment for primary resectable GIST. Completely resectable GIST with low risk has excellent prognosis after primary surgical intervention, with over 90% of the 5-year survival. We report a case of 10-year-old girl presenting with an upper gastrointestinal bleeding caused by gastrointestinal stromal tumor.

Recurrence Patterns and Clinical Behavior of Gastrointestinal Stromal Tumors (GISTs)

PURPOSE: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasm of the gastrointestinal (GI) tract, and account for 1% of all GI malignancies. GISTs have a highly variable clinical course, and recurrent disease sometimes develops despite curative treatment. Although there are several known risk factors for recurrence, there are few adequate treatment strategies. This study evaluated the clinical behavior and clinicopathological characteristics, and examined correlation between recurrence and the prognostic factors. METHODS: From March 1999 to December 2005, 41 patients, with GISTs confirmed by a pathologic examination after a surgical resection, were enrolled. The patients were evaluated by immunohistochemical staining for CD117, CD34 and smooth muscle actin, and were classified according to the NIH criteria. RESULTS: The mean age was 58.9 years and the GISTs were mainly located in the stomach (56%) and small bowel (32%). With a median follow-up of 17.4 months, recurrence of the disease occurred in nine (22%) patients, with the liver being the main organ involved. According to the NIH criteria, there were 2 very low risk tumors, 11 low risk, 16 intermediate, and 12 high risk diagnosed. Gender was found to have predictive value for a recurrence (P=0.05). CONCLUSION: The primary site and gender have predictive value for a recurrence. Identifying the risk factors for recurrent disease may be useful for planning follow-up schedules. Further study involving more cases and a long-term follow-up will be needed. In addition, pathologic and immunohistoche-mical studies will be required to reduce the recurrence rate after a resection and to improve the patients' outcome.

Gastrointestinal Stromal Tumor Accompanied with von Recklinghausen's Disease: Positive for CD117, CD34, SMA and S-100 Protein

Gastrointestinal stromal tumors (GISTs) are CD117-positive primary mesenchymal tumors of the gastrointestinal tract and they have a characteristic set of morphologic features. GISTs have been noted to have a possible non-random association with neurofibromatosis-1 (NF-1, von Recklinghausen disease). We report here on a case of multiple GISTs with abundant skenoid fiber in the jejunum of a 47-year-old woman, and this condition was accompanied with NF-1. The tumor cells coexpressed smooth muscle actin, S-100 protein, CD117 and CD34. These immunohistochemical results are extremely rare findings for GISTs accompanying with NF-1. We think this is the first report of GISTs arising within NF-1 with the dual immunohistochemical differentiation of neuronal and muscular markers.

Analysis of Prognostic Factors in Gastrointestinal Stromal Tumors

PURPOSE: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract and are immunohistochemically defined as c-KIT (CD117) positive tumors. This study investigated the behaviors of GISTs of the gastrointestinal tract and determined the prognostic factors associated with GISTs. METHOD: The clinical records of 22 patients, who were diagnosed and underwent surgery for a GIST of the GI tract at Inje university Sanggye Paik hospital from 1998 to 2004, were retrospectively analyzed. The relationship between the disease-free survival rate of the GISTs and several factors including age, gender, mitotic count, tumor site, tumor size, tumor necrosis & hemorrhage, and Ki-67 index was examined. RESULTS: The study group comprised of 13 men and 9 women. The mean age was 57.1 years (31~77 years) at the time of diagnosis. The median follow-up period was 24 months (3~45 months). A complete resection of the tumor was performed in 19 patients. There were lymph node metastases in 1 case. Five out of the 19 patients who had undergone a complete tumor resection showed recurrence (27%). The sites of recurrence were the back (1), liver (1), and abdominal cavity (3). Univariate analysis revealed, the following to be prognostic factors for the disease-free survival of patients with GISTs: high power field mitotic counts of the tumor ( or =5/50; P=0.013), the tumor size ( or =5 cm; P=0.047) and the Ki-67 index ( or =5%; P=0.001). CONCLUSION: The prognostic factors for disease-free survival rate of GISTs were high power field mitotic counts of the tumor, the tumor size and the Ki-67 index. It is recommended that more careful and frequent postoperative follow-up examinations be performed for patients showing the poor prognostic factors.

Multiple Gastrointestinal Stromal Tumors of the Small Intestine

Gastrointestinal stromal tumors (GISTs) are a heterogeneous group of mesenchymal neoplasms of the gastrointestinal tract. A great majority of GISTs occur in the stomach and small intestine, but multiple GISTs of the jejunum are rare. We experienced a case of multiple GISTs of the jejunum. A 57 year old woman was admitted due to general weakness and abdominal pain. The computer tomography of the abdomen revealed solid tumor in the jejunum. We removed tumor from jejunum by resection. Histological and immunohistochemical studies revealed a gastrointestinal stromal tumor of the intermediate malignant type.

Value of Elevated Ki67 Index (>10%) and p53 Protein Expression as Prognostic Factors in GISTs

PURPOSE: Although gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors and express CD117, the prediction of their malignant potential remains difficult. The aim of this study is to evaluate the prognostic accuracy of elevated Ki67 index and p53 overexpression in combination with classical prognostic factors (tumor size and mitotic index). METHODS: A retrospective study was conducted in 84 patients who had been re-evaluated for confirmation of diagnosis based on immunohistochemical analysis with CD117 expression, between Jan 1991 and Dec 2001. Cases were classified as very low, low, intermediate and high-risk groups according to 2001 NIH consensus symposium. Elevated Ki67 index was assigned to the lesion that displayed 10% or more of immunoreactive cells. And p53 expression was assigned to the area with 5% or more of eosinophilic nucleus. RESULTS: Elevated Ki67 was noted in 37 (44.0%) out of 84 cases. High-risk patients showed elevated Ki67 index more frequently (P<0.0001) and there was significant relation between elevated Ki67 and survival rate (P=0.0417). The p53 expression was noted in 32 (38.1%) out of 84 cases. The p53 expression was significantly higher in high-risk patients (P=0.0081) than low-risk patients. But, there was no significant relation between p53 expression and survival rate. As a result of multivariate analysis, tumor size (P=0.0059), mitotic index (P=0.0016) and elevated Ki67 index (P=0.0384) were proved as significant independent prognostic factors. CONCLUSION: According to the results of our retrospective study, p53 expression is related to disease progression but its value as a prognostic factor in GISTs is uncertain. It is suggested that tumor size, mitotic rate and elevated Ki67 index are the helpful prognostic factors in GISTs.

Gastrointestinal Stromal Tumors (GISTs) of the Colon and Rectum: Clinicopathological Analysis

PURPOSE: This study was undertaken to investigate the clinicopathological features of GISTs (gastrointestinal stromal tumors) of the colon and rectum. Method: At Seoul National University Hospital from Jan. 1994 to Dec. 2002, 11 patients were diagnosed as having GISTs, leiomyomas, or leiomyosarcomas of the colon and rectum. For those 11 patients, immunohistochemical staining for CD117 (c-kit) was undertaken in order to differentiate true GISTs from leiomyomas and leiomyosarcomas. Ten patients were positive for CD117 (c-kit) and were finally diagnosed as having GISTs. Then, we retrospectively analyzed the clinical and the pathological features of those 10 cases and investigated the recurrence of disease and the survival. RESULTS: Colorectal GISTs accounted for 0.3% of all colorectal malignancies (10 cases/2,964 cases). The male- female ratio for the 10 patients with GISTs was 8:2, and the median age was 56.5 (34~75) years. The locations of the tumor were the rectum in 9 cases (90%) and the ascending colon in 1 case. The most common symptoms were decreased stool caliber and GI bleeding (3 cases, respectively). A curative-intent resection was possible in 8 cases. There were two cases of recurrence after curative resection (25.0%). The median survival period of the 10 patients was 33.5 (2~70) months. The median tumor size was 7.5 (5~20) cm, and the median number of mitosis per 50 high-power fields was 36.5 (8~123). There was a statistically significant correlation between size and mitotic count (r=0.942, P=0.001). CONCLUSIONS: Colorectal GISTs are very rare disease entities (0.3% of the colorectal malignancies). However, all colorectal GISTs were classified as malignant based on their sizes and mitotic counts in our study. For introduction of STI-571 in the treatment of colorectal GISTs and for further study, accurate diagnosis of GISTs by special immunohistochemical staining (c-kit) is very important in differential diagnosis of primary gastrointestinal mesenchymal tumors and recurred leiomyosarcomas.

Clinical Effectiveness of Diagnosis Using Immunohistochemistry and New Grade in Gastrointestinal Stromal Tumors (GISTs)

PURPOSE: Paraffin-embedded tissue samples from the gastrointestinal tract, which had been diagnosed as tumors of a mesenchymal origin, were reviewed by an immunohistochemical staining method. The prognostic significances of the immunohistochemical subtypes and anatomical locations were also investigated. GIST, as a new grading system, was compared with the pre-existing system for its useful prognostic significance. METHODS: 122 cases were evaluated and classified by immunohistochemical staining for KIT, CD34, actin, desmin, vimentin, S-100 protein and NSE. RESULTS: Positivity for both KIT and CD34 of 92.6 and 73.8%, respectively, indicated that KIT was more effective for the diagnosis of GISTs. The stomach (62.3%) and small bowel (23.7%) were most common organs of GIST. There was no difference in the prognosis between these two organs. Immunophenotypically, the uncommitted, myoid, combined and neural types were 37.7, 23.7, 20.2 and 7%, respectively. There was no significant difference in the prognosis between these types. The old grading system showed no difference between the borderline and malignant groups (P=0.14), whereas, the new grading system showed a significant difference between the intermediate and high risk groups (P=0.01). CONCLUSION: KIT is more useful for the diagnosis of GOSTs. The immunophenotypical classification and anatomical location showed no prognostic significance in GISTs. Therefore, the new grading system might be more useful than older system.

Clinical Evaluation of Gastrointestinal Stromal Tumor of Stomach

PURPOSE: The aim of this study was to analyze the outcomes of patients with gastrointestinal stromal tumors (GISTs) of the stomach who were treated in our hospital. MATENRIALS AND METHODS: We retrospectively studied 31 patients who were treated for primary gastrointestinal stromal tumors of the stomach from 1990 to 1999 at Korea University Guro Hospital. Clinical characteristics, including age, sex and tumor size were analyzed. In addition, the relation between the 5-year survival rate and tumor size, operative procedure, and malignancy were analyzed to identify the factors that predict survival. RESULTS: The malignant GISTs were 11 cases, borderline GISTs were 2 cases, and benign GISTs were 18 cases. The overall 5-year cumulative survival rate of the patients was 84.6%, and the 5-year survival rates according to malignancy were 100% for benign and borderline GISTs and 78.1% for malignant GISTs, p=0.1119. The 5-year survival rates according to tumor size were 100% for tumor sizes smaller than 5 cm and 78.4% for tumor sizes larger than 5 cm, p=0.0453. The 5-year survival rate according to lymph node dissection during operative procedure of malignant GISTs was not significant statistically. CONCLUSION: GISTs of the stomach are infrequently encountered tumors. Tumor size was the most important factor for predicting survival in a clinical situation, and performing a complete resection of the tumor, especially tumors larger than 5 cm, will improve the outcome of treatment.