Deep learning model combined with computed tomography features to preoperatively predicting the risk stratification of gastrointestinal stromal tumors

BACKGROUND Gastrointestinal stromal tumors(GIST)are prevalent neoplasm originating from the gastrointestinal mesenchyme.Approximately 50%of GIST patients experience tumor recurrence within 5 years.Thus,there is a pressing need to accurately evaluate risk stratification preoperatively.AIM To assess the application of a deep learning model(DLM)combined with computed tomography features for predicting risk stratification of GISTs.METHODS Preoperative contrast-enhanced computed tomography(CECT)images of 551 GIST patients were retrospectively analyzed.All image features were independently analyzed by two radiologists.Quantitative parameters were statistically analyzed to identify significant predictors of high-risk malignancy.Patients were randomly assigned to the training(n=386)and validation cohorts(n=165).A DLM and a combined DLM were established for predicting the GIST risk stratification using convolutional neural network and subsequently evaluated in the validation cohort.RESULTS Among the analyzed CECT image features,tumor size,ulceration,and enlarged feeding vessels were identified as significant risk predictors(P<0.05).In DLM,the overall area under the receiver operating characteristic curve(AUROC)was 0.88,with the accuracy(ACC)and AUROCs for each stratification being 87%and 0.96 for low-risk,79%and 0.74 for intermediate-risk,and 84%and 0.90 for high-risk,respectively.The overall ACC and AUROC were 84%and 0.94 in the combined model.The ACC and AUROCs for each risk stratification were 92%and 0.97 for low-risk,87%and 0.83 for intermediate-risk,and 90%and 0.96 for high-risk,respectively.Differences in AUROCs for each risk stratification between the two models were significant(P<0.05).CONCLUSION A combined DLM with satisfactory performance for preoperatively predicting GIST stratifications was developed using routine computed tomography data,demonstrating superiority compared to DLM.

Comparison of endoscopic and laparoscopic resection of gastric gastrointestinal stromal tumors:A propensity score-matched study

BACKGROUND Endoscopic resection(ER)and laparoscopic resection(LR)have been widely used for the treatment of non-metastatic gastric gastrointestinal stromal tumors(gGISTs)(2-5 cm),but there are no selection criteria for their application.AIM To provide a reference for the development of standardized treatment strategies for gGISTs.METHODS Clinical baseline characteristics,histopathological results,and short-term and long-term outcomes of patients who treated with ER or LR for gGISTs of 2-5 cm in Taizhou Hospital of Zhejiang Province from January 2014 to August 2022 were retrospectively reviewed.Propensity score matching(PSM)was employed to achieve balance in baseline characteristics of the two groups.RESULTS Among 206 patients,135 were in the ER group and 71 in the LR group.The ER group had significantly smaller tumors[3.5 cm(3.0-4.0 cm)vs 4.2 cm(3.3-5.0 cm),P<0.001]and different tumor locations(P=0.048).After PSM,59 pairs of patients were balanced.After matching,the baseline characteristics of the ER and LR groups did not differ significantly from each other.Compared with LR,ER had faster recovery of diet(P=0.046)and fewer postoperative symptoms(P=0.040).LR achieved a higher complete resection rate(P<0.001)and shorter operation time(P<0.001).No significant differences were observed in postoperative hospital stay(P=0.478),hospital costs(P=0.469),complication rates(P>0.999),pathological features(mitosis,P=0.262;National Institutes of Health risk classification,P=0.145),recurrence rates(P=0.476),or mortality rates(P=0.611).CONCLUSION Both ER and LR are safe and effective treatments for gGISTs.ER has less postoperative pain and faster recovery,while LR has a higher rate of complete resection.

Study on vasculogenic mimicry in malignant esophageal stromal tumors

AIM: To investigate whether malignant esophageal stromal tumors contain PAS-positive patterned matrix-associated vascular channels, which are lined by tumor cells, but not vascular endothelial cells. That is vasculogenic mimicry (VM) independent of tumor angiogenesis. METHODS: Thirty-six tissue samples of malignant esophageal stromal tumors were analyzed. Tissue sections were stained for Vascular endothelial growth factor (VEGF), CD31 and periodic acid Schiff (PAS). The level of VEGF, the microvascular density (MVD) and the vasculogenic mimicry density (VMD) were determined. RESULTS: PAS-positive patterned matrix-associated vascular channels were detected in 33.3% (12/36) of tumor samples. Within these patterned channels, red blood cells were found. The level of VEGF and the MVD in tumors containing patterned channels were significantly higher than those in tumors not containing patterned channels (P < 0.05). At the same time, the malignant degree of tumors was higher, the proportions of tumors containing patterned channels were not only more, but also in the each kind of tumors containing patterned channels. CONCLUSION: In malignant esophageal stromal tumors, a VM mechanism causes some tumor cells to deform themselves and secrete extracellular matrix; thus, PAS-positive patterned matrix-associated vascular channels appear and supplying blood to the tumors to sustain their growth and metastasis.

Molecular regulation of vasculogenic mimicry in tumors and potential tumor-target therapy

"Vasculogenic mimicry(VM)",is a term that describes the unique ability of highly aggressive tumor cells to express a multipotent,stem cell-like phenotype,and form a pattern of vasculogenic-like networks in threedimensional culture.As an angiogenesis-independent pathway,VM and/or periodic acid-schiff-positive patterns are associated with poor prognosis in tumor patients.Moreover,VM is resistant to angiogenesis inhibitors.Here,we will review the advances in research on biochemical and molecular signaling pathways of VM in tumors and on potential anti-VM therapy strategy.

Prognostic significance of PTEN,Ki-67 and CD44s expression patterns in gastrointestinal stromal tumors

AIM:To develop a prognostic approach for gastrointestinal stromal tumors(GISTs) using a cluster of indicators and follow-up information.METHODS:One hundred and four GISTs that had not been subjected to targeted therapies were collected and classified by NIH risk assessment and anatomic location.By immunohistochemistry,the expressions of PTEN,Ki-67,CD44s matrix metalloproteinase(MMP)-9 and TIMP-1 were detected on tissue microarray.Univariate and multimarker survival analyses were performed and then a COX hazard proportion model was constructed to evaluate a cluster of predictors of GIST.RESULTS:Our data showed small intestinal GIST are more aggressive than gastric GIST.The NIH risk assessment correlated with disease-free survival foreither gastric GIST or small intestinal GIST.Immunohistochemical analysis revealed that Ki-67 labeling indexes(LIs) < 5% predicted higher disease-specific survival(DSS) in gastric and small intestinal GIST.CD44s positivity and PTEN LIs ≥ 50% correlated with higher DSS in gastric GIST.MMP-9 and TIMP-1 had no correlation with survival.Multimarker analysis revealed that the expression pattern of PTEN LIs ≥ 50% combined with Ki-67 LIs < 5% and CD44s positivity reliably predicted favorable outcomes for gastric GIST(P = 0.009),as did the combination of PTEN LIs ≥ 50% and Ki-67 LIs < 5% for small intestinal GIST(P = 0.011).Authors also found that high NIH risk grade was correlated with DSS in patients with gastric GIST and disease-free survival in patients with small intestinal GIST.CONCLUSION:PTEN LIs ≥ 50%,Ki-67 LIs < 5% and CD44s positivity provides an accurate,favorable prognosis for gastric GIST.PTEN LIs ≥ 50% and Ki-67 LIs < 5% does the same for small intestinal GIST.Ki-67 LIs enhances the NIH assessment.

Comparison of short-and long-term outcomes of laparoscopic vs open resection for gastric gastrointestinal stromal tumors

AIM To compare the short-and long-term outcomes of laparoscopic(LR) vs open resection(OR) for gastric gastrointestinal stromal tumors(g GISTs).METHODS In total, 301 consecutive patients undergoing LR or OR for pathologically confirmed g GISTs from 2005 to 2014 were enrolled in this retrospective study. After exclusion of 77 patients, 224 eligible patients were enrolled(122 undergoing LR and 102 undergoing OR). The demographic, clinicopathologic, and survival data of all patients were collected. The intraoperative, postoperative, and long-term oncologic outcomes were compared between the LR and OR groups following the propensity score matching to balance the measured covariates between the two groups.RESULTS After 1:1 propensity score matching for the set of covariates including age, sex, body mass index, American Society of Anesthesiology score, tumor location, tumor size, surgical procedures, mitotic count, and risk stratification, 80 patients in each group were included in the final analysis. The baseline parameters of the two groups were comparable after matching. TheLR group was significantly superior to the OR group with respect to the operative time, intraoperative blood loss, postoperative first flatus, time to oral intake, and postoperative hospital stay(P < 0.05). No differences in perioperative blood transfusion or the incidence of postoperative complications were observed between the two groups(P > 0.05). No significant difference was found in postoperative adjuvant therapy(P = 0.587). The mean follow-up time was 35.30 ± 26.02(range, 4-102) mo in the LR group and 40.99 ± 25.07(range, 4-122) mo in the OR group with no significant difference(P = 0.161). Survival analysis showed no significant difference in the disease-free survival time or overall survival time between the two groups(P > 0.05).CONCLUSION Laparoscopic surgery for g GISTs is superior to open surgery with respect to intraoperative parameters and postoperative outcomes without compromising longterm oncological outcomes.

Prognostic value of fibrinogen and D-dimer-fibrinogen ratio in resectable gastrointestinal stromal tumors

AIM To investigate the prognostic value of preoperative fbri-nogen concentration （FIB） and D-dimer-fibrinogen ratio （DFR） in gastrointestinal stromal tumors （GISTs）.METHODS The purpose of this study was to retrospectively ana-lyze 170 patients with GISTs who were admitted to our hospital from January 2010 to December 2015. The op-timal cutoff values of related parameters were estimated by receiver operating characteristic （ROC） curve analysis. The recurrence free survival （RFS） rate was evaluated using Kaplan-Meier curves. Univariate analysis and multivariate Cox regression models were used to analyze the prognostic factors of GISTs. The relationship between the FIB, D-dimer, DFR, platelet count （PLT）, and the clinicopathological features of GISTs was described by the chi-square test or nonparametric rank sum test （Mann-Whitney test）.RESULTS In ROC analysis, the optimal cutoff values of FIB, D-dimer, DFR, and PLT were 3.24 g/L, 1.24 mg/L, 0.354, and 197.5 （× 109/L）, respectively. Univariate analysis and the Kaplan-Meier survival curve showed that FIB, D-dimer, DFR, PLT,National Institutes of Health （NIH） risk category, tumor size, tumor location, and mitotic index were signifcantly relevant to the 3-year and 5-year survival rate of patients （ P 〈 0.05）. Cox multivariate regression analysis illustrated that FIB （RR： 0.108, 95%CI： 0.031-0.373）, DFR （RR： 0.319, 95%CI： 0.131-0.777）, and NIH risk category （ RR： 0.166, 95%CI： 0.047-0.589） were independent prognostic factors of the RFS rate （ P 〈 0. 05）. Moreover, FIB, D-dimer, DFR, and PLT were correlated with the clinical features of GISTs.CONCLUSIONFIB, D-dimer, DFR, and PLT are all related to the prognosis of GISTs. Moreover, FIB and DFR may be independent risk factors for predicting the prognosis of resectable GISTs.

Evaluation of malignancy using Ki-67,p53,EGFR and COX-2 expressions in gastrointestinal stromal tumors

AIM:To investigate the role of expressions of Ki-67, p53,epidermal growth factor receptor(EGFR)and cyclooxygenase-2(COX-2)in gastrointestinal stromal tumor(GIST)grading and prognosis. METHODS:Tumor tissue was collected retrospectively from 96 patients with GIST.Antibodies against Ki-67, p53,EGFR and COX-2 were used for immunohistochemical staining.Tumor grading was designated according to a consensus system and the staining was quantified in 3 categories for each antibody in the statistical analysis. RESULTS:The Ki-67 expression in GISTs was significantly associated with the size of the tumors,mitotic rate and the risk of malignancy(x2=15.51,P=0.02; x2=22.27,P<0.001;x2=20.05;P<0.001).The p53 expression was also significantly correlated with mitotic rate and the risk of malignancy(x2=9.92,P= 0.04;x2=9.97;P=0.04).Over-expression of Ki-67 was strongly correlated with poor survival(x2=10.44, P=0.006),but no correlation was found between the expression of p53,EGFR or COX-2 and survival. Multivariate analysis further demonstrated that Ki-67 expression(relative risk=15.78,95%CI:4.25-59.37) could be used as an independent prognostic value for GIST patients.Adjuvant imatinib therapy could improve clinical outcomes in the patients with high risk and intermediate risk of recurrence after complete tumor resections(median survival time:52 mo vs 37 mo, x2=7.618,P=0.006). CONCLUSION:Our results indicated that the expression of Ki-67 could be used as an independent prognostic factor for GIST patients.

DNA ploidy and c-Kitmutation in gastrointestinal stromal tumors

AIM: To investigate the prognostic significance of c-Kitgen emutation and DNA ploidy in gastointestinal stromal tumors (GISTs).METHODS: A total of 55 cases of GISTs were studied for the expression of c-Kit by immunohistochemistry, and the c-Kit gene mutations in exons 9, 11, 13, and 17 were detected by polymerase chain reaction-single strand confirmation polymarphism (PCR-SSCP) and denaturing high performance liquid chromatography (D-HPLC) techniques. DNA ploidy was determined by flow cytometry.RESULTS: Of the 55 cases of GISTs, 53 cases (96.4%) expressed c-Kit protein. The c-Kit gene mutations of exons 11 and 9 were found in 30 (54.5%) and 7 cases (12.7%),respectively. No mutations were found in exons 13 and 17.DNA aneuploidy was seen in 10 cases (18.2%). The c-Kit mutation positive GISTs were larger in size than the negative GISTs. The aneuploidy tumors were statistically associated with large size, high mitotic counts, high risk groups, high cellularity and severe nuclear atypia, and epithelioid type.There was a tendency that c-Kit mutations were more frequently found in aneuploidy GISTs.CONCLUSION: DNA aneuploidy and c-Kit mutations can be considered as prognostic factors in GISTs.

Clinical and prognostic significance of CC chemokine receptor type 8 protein expression in gastrointestinal stromal tumors

BACKGROUND Gastrointestinal stromal tumors(GISTs)are the most common mesenchymal neoplasms of the gastrointestinal tract.Surgical resection and tyrosine kinase inhibitors are defined as the main treatments but cannot cure patients with advanced GIST,which eventually develops into recurrence and acquired drug resistance.Therefore,it is necessary to identify prognostic biomarkers and new therapeutic targets for GISTs.CC chemokine receptor type 8(CCR8)protein participates in regulation of immune responses.Recent studies on CCR8 in nonsmall cell lung cancer and colorectal cancer showed that it was highly expressed in tumor-infiltrating regulatory T cells and correlated with a poor prognosis.AIM To detect CCR8 expression in GIST tissues and analyze its relationships with clinicopathological features and prognosis in patients with GISTs.METHODS Tissue samples were used for the tissue microarrays construction.The microarrays were then subjected to immunohistochemical analyses to detect CCR8 expression.Next,Kaplan–Meier analysis was utilized to calculate the survival rate of patients with complete follow-up data,and the potential prognostic value of CCR8 was evaluated by Cox regression analysis.Finally,a Gene Ontology/Kyoto Encyclopedia of Genes and Genomes single-gene enrichment chart of CCR8 was constructed using the STRING database.RESULTS CCR8-positive signals were detected as brown or brown-yellow particles by immunohistochemistry located in the cytoplasm.Among 125 tissue samples,74 had CCR8 high expression and 51 had low or negative expression.Statistical analyses suggested CCR8 was significantly correlated with tumor size,mitotic index,AFIP-Miettinen risk classification and tumor location.Kaplan–Meier and multivariate analyses showed that patients with low or negative CCR8 expression,mitotic index<5/high-power fields(HPF)and tumor diameter<5 cm had a better prognosis.Based on the STRING database,CCR8 was significantly enriched in biological processes such as tumor immunity,T lymphocyte chemotaxis,migration and pathways like the nuclear factor-κB and tumor necrosis factor pathways as well as intestinal immune regulation networks.CONCLUSION CCR8 is a prognostic biomarker for malignant potential of GISTs,with high expression correlated with malignancy and poor prognosis.

Performance of risk stratification systems for gastrointestinal stromal tumors: A multicenter study

BACKGROUND Gastrointestinal stromal tumors(GISTs) are the most common mesenchymal tumor type in the gastrointestinal system. Presently, various classification systems to prognosticate GISTs have been proposed.AIM To evaluate the application value of four different risk stratification systems for GISTs.METHODS Patients who were diagnosed with GISTs and underwent surgical resection at four hospitals from 1998 to 2015 were identified from a database. Risk of recurrence was stratified by the modified National Institute of Health(NIH)criteria, the Armed Forces Institute of Pathology(AFIP) criteria, the Memorial Sloan Kettering Cancer Center(MSKCC) prognostic nomogram, and the contour maps. Receiver operating characteristic(ROC) curves were established to compare the four abovementioned risk stratification systems based on the area under the curve(AUC).RESULTS A total of 1303 patients were included in the study. The mean age of the patients was 55.77 ± 13.70 yr; 52.3% of the patients were male. The mean follow-up period was 64.91 ± 35.79 mo. Approximately 67.0% the tumors were located in the stomach, and 59.5% were smaller than 5 cm; 67.3% of the patients had a mitotic count ≤ 5/50 high-power fields(HPFs). Thirty-four tumors ruptured before and during surgery. Univariate analysis demonstrated that tumor size > 5 cm(P <0.05), mitotic count > 5/50 HPFs(P < 0.05), non-gastric location(P < 0.05), and tumor rupture(P < 0.05) were significantly associated with increased recurrence rates. According to the ROC curve, the AFIP criteria showed the largest AUC(0.754).CONCLUSION According to our data, the AFIP criteria were associated with a larger AUC than the NIH modified criteria, the MSKCC nomogram, and the contour maps, which might indicate that the AFIP criteria have better accuracy to support therapeutic decision-making for patients with GISTs.

Prognostic factors of primary gastrointestinal stromal tumors： a cohort study based on high-volume centers

Objective： We aimed to evaluate the clinicopathologic characteristics, immunohistochemical expression and prognostic factors of patients with primary gastrointestinal stromal tumors（GISTs）.Methods： Data from 2,570 consecutive GIST patients from four medical centers in China（January2001–December 2015） were reviewed. Survival curves were constructed by the Kaplan-Meier method, and Cox regression models were used to identify independent prognostic factors.Results： Of the included patients, 1,375（53.5%） were male, and the patient age range was 18 to 95（median, 58）years. The tumors were mostly found in the stomach（64.5%）, small intestine（25.1%） and colorectal region（5.1%）.At the time of diagnosis, the median tumor size was 4.0（range： 0.1–55.0） cm, and the median mitotic index per 50 high power fields（HPFs） was 3（range： 0–254）. Of the 2,168 resected patients, 2,009（92.7%） received curative resection. According to the modified National Institutes of Health（NIH） classification, 21.9%, 28.9%, 14.1% and35.1% were very low-, low-, intermediate-and high-risk tumors, respectively. The rate of positivity was 96.4% for c-Kit, 87.1% for CD34, 96.9% for delay of germination 1（DOG-1）, 8.0% for S-100, 31.0% for smooth muscle actin（SMA） and 5.1% for desmin. However, the prognostic value of each was limited. Multivariate analysis showed that age, tumor size, mitotic index, tumor site, occurrence of curative resection and postoperative imatinib were independent prognostic factors. Furthermore, we found that high-risk patients benefited significantly from postoperative imatinib（P〈0.001）, whereas intermediate-risk patients did not（P=0.954）.Conclusions： Age, tumor size, mitotic index, tumor site, occurrence of curative resection and postoperative imatinib were independent prognostic factors in patients with GISTs. Moreover, determining whether intermediate-risk patients can benefit from adjuvant imatinib would be of considerable interest in future studies.

Prognostic significance of hemoglobin,albumin,lymphocyte,platelet in gastrointestinal stromal tumors:A propensity matched retrospective cohort study

BACKGROUND The combined index of hemoglobin,albumin,lymphocyte,and platelet(HALP)can reflect systemic inflammation and nutritional status simultaneously,with some evidence revealing its prognostic value for some tumors.However,the effect of HALP on recurrence-free survival(RFS)in patients with gastrointestinal stromal tumors(GISTs)has not been reported.AIM To investigate the prognostic value of HALP in GIST patients.METHODS Data from 591 untreated patients who underwent R0 resection for primary and localized GISTs at West China Hospital between December 2008 and December 2016 were included.Clinicopathological data,preoperative albumin,blood routine information,postoperative treatment,and recurrence status were recorded.To eliminate baseline inequivalence,the propensity scores matching(PSM)method was introduced.Ultimately,the relationship between RFS and preoperative HALP was investigated.RESULTS The optimal cutoff value for HALP was determined to be 31.5 by X-tile analysis.HALP was significantly associated with tumor site,tumor size,mitosis,Ki67,National Institutes of Health(NIH)risk category,and adjuvant therapy(all P<0.001).Before PSM,GIST patients with an increased HALP had a significantly poor RFS(P<0.001),and low HALP was an independent risk factor for poor RFS[hazard ratio(HR):0.506,95%confidence interval(95%CI):0.291-0.879,P=0.016].In NIH high-risk GIST patients,GIST patients with low HALP had a worse RFS than patients with high HALP(P<0.05).After PSM,458 GIST patients were identified;those with an increased HALP still had significantly poor RFS after PSM(P<0.001)and low HALP was still an independent risk factor for poor RFS(HR:0.558,95%CI:0.319-0.976,P=0.041).CONCLUSION HALP was significantly correlated with postoperative pathology and postoperative treatment.Furthermore,HALP showed a strong ability to predict RFS in GIST patients who underwent radical resection.

Clinicopathological characteristics and longterm survival of patients with synchronous multiple primary gastrointestinal stromal tumors: A propensity score matching analysis

BACKGROUND Multiple gastrointestinal stromal tumors(MGISTs)are specific and rare.Little is known about the impact of MGISTs on the survival of patients with gastrointestinal stromal tumors(GIST).The diagnosis,treatment and follow-up strategies of MGISTs is not specifically described in guidelines.AIM To compare the clinicopathological characteristics and prognosis of MGISTs and solitary GISTs(SGISTs)METHODS Patients diagnosed with primary GISTs from March 2010 to January 2020 were included.Due to the inhomogeneous distribution of several baseline characteristics and uneven MGIST and SGIST group sizes,propensity score matching was performed according to comorbidities,body mass index,tumor location,mitotic index,sex,age and American Society of Anesthesiologists score.Differences in clinicopathological characteristics and prognosis between patients with MGISTs and patients with SGISTs were compared.RESULTS Among the entire cohort of 983 patients,the incidence of MGISTs was 4.17%.Before matching,patients with MGISTs and those with SGISTs had disparities in body mass index,surgical approach,tumor size and mitotic index.After 1:4 ratio matching,the clinical baseline data were comparable.The 5-year progression-free survival rate was 52.17%in the MGIST group and 75.00%in the SGIST group(P=0.031).On multivariate analysis,tumor location,tumor size,mitotic index,imatinib treatment and MGISTs(hazard ratio=2.431,95%confidence interval=1.097-5.386,P=0.029)were identified as independent prognostic factors of progression-free survival.However,overall survival was similar between the SGIST and MGIST groups.CONCLUSION Patients with MGISTs had poorer progression-free survival than patients with SGISTs.Risk criteria and diagnostic and treatment strategies should be developed to achieve personalized precision therapy and maximize the survival benefit.

Gastrointestinal Stromal Tumors: Correlation of Multislice CT Findings to Histopathologic Features and Preliminary Validation of New Scoring System

Purpose: The purpose of this study is to demonstrate the correlation between radiologic and pathologic features of the gastrointestinal stromal tumors. Patients and methods: A retrospective review from 2004 to 2014 identified 50 resected cases of confirmed gastrointestinal stromal tumors (GIST) is done. All these lesions were visualized in the first multi-slice computed tomography (MSCT) investigation. Radiologic and pathologic features were reviewed and compared. A radiologic score with MSCT findings was established. Four levels of risk were defined and compared to the Miettinen-Lasota prognostic classification. Results: Mean patients’ age was 57.6 with a sex-ratio (M/F) of 1.17. Of the 50 GISTs lesions, 29 were located in the stomach (58%), 3 in the duodenum (6%), 16 in the small intestine (32%), one in the rectum and one in the great omentum. MSCT images were evaluated for origin and size of the tumor, as well as growth pattern, density before and after contrast, relationship with adjacent structures, presence of lymph nodes, ascitis and metastasis. The presence of mucosal ulceration, calcification, necrosis, cystic area or hemorrhage into the lesion was emphasized for each case. The histologic equivalent criteria were gathered from histopathology examination review of all specimens. Significant correlation was found for all these findings except the hemorrhage (p = 0.071). A radiologic score of fifteen items variable between 0 and 18 was established. Miettinen risk classification was noted for each lesion. GISTs with very low risk had MSCT score < 4. GIST with low risk had a MSCT score between 5 and 9. GIST with moderate risk had a score between 10 and 14 and those with high risk had an MSCT score between 15 and 18. Significant correlation was found between the radiologic and histopathologic risk classification (p = 0. 001). Conclusion: MSCT is helpful in risk prediction for GIST.

Prognositic factors and clinicopathologic characteristics of small gastrointestinal stromal tumor of the stomach:a retrospective analysis of 31 cases in one center

Objective： To analyze the clinicopathologic characteristics and prognostic factors of small gastrointestinal stromal tumor （GIST） of the stomach. Methods： A total of 31 small gastric GIST patients, including 10 males and 21 females, with a median age of 58 years （37- 81 years）, who underwent surgery at any time from 1999 to 2012 were included in this study. The clinical records of the patients were analyzed retrospectively. Results： Abdominal discomfort and pain （10 cases, 32.3%, respectively） were the two most common complaints among the patients. All patients received surgery, 11 received gastric wedge resection, 11 received subtotal gastrectom）5 5 received laparoscopic gastric wedge resection, and 4 received endoscopic submucosal dissection. No severe adverse complication was observed. A total of 29 patients （93.5%） were followed up. During the follow-up, 2 patients were found to exhibit tumor recurrence, and 1 patient had liver metastases. One patient died of tumor progressionwhile another died of another malignant tumor. Median progression free survival （PFS） time was 120.3 months, and median overall survival （OS） time was 130.4 months. Conclusion： Small gastric GIST has better prognosis. Surgery is the best choice for therapy. Micro-invasive procedures are safe and effective for elective patients. Tumor necrosis, tumor bleeding, and muscle invasion are potential prognostic factors of small gastric GIST.

Reduced Expression of PTEN Protein and Its Prognostic Significance in the Gastrointestinal Stromal Tumor

Little is reported about the role of PTEN gene in the progression and prognosis of GISTs. This study examined the clinical implications of the tumor suppressor gene PTEN as a prognostic factor in the GISTs. Immunohistological staining and immunoblotting were employed to examine the PTEN protein expression, and its association with clinical measures. Clinicopathological features were reviewed by a retrospective examination of medical records. Reduced PTEN expression was significantly associated with tumor diameter, mitotic figure count, metastasis and pathological stage of tumor （P〈0.05）, and was not correlated with age, gender and tumor location （P〉0.05）. The 3-year survival rate of the patients with reduced PTEN expression was significantly lower than those with high PTEN expression （P〈0.01）. These results suggest that the expression of PTEN gene was significantly linked with the progression and metastasis of GISTs and it is an independent prognostic factor.

Loss of chromosome 9p21 and decreased p16 expression correlate with malignant gastrointestinal stromal tumor

AIM: To investigate loss of heterozygosity (LOH) of chromosome 9p21 and the prognostic relevance of p16 expression in gastrointestinal stromal tumor (GIST). METHODS: Fifty-one GIST patients (30 men and 21 women; median age 59 years; range 29-80 years) treated surgically within a 10-year period were grouped by aggressive behavior risk (17 with very low and low, 14 intermediate, and 20 high risk). GISTs were characterized immunohistochemically and evaluated for LOH of 9p21 by microsatellite analysis at D9S1751, D9S1846, D9S942, and D9S1748. LOH of 9p21 and immunohistochemicalexpression of p16 protein encoded at 9p21 were correlated with clinicopathological parameters, and the prognostic significance of p16 alterations was evaluated. RESULTS: Thirty-one (63.3%) cases showed LOH with at least one microsatellite marker. LOH frequency was 37.0% at D9S1751, 37.5% at D9S1846, 42.1% at D9S942, and 24.2% at D9S1748. There was a higher LOH frequency of D9S942 in high-risk than in non-highrisk tumors (P < 0.05, χ 2 = 4.47). Gender, age, tumor size and site were not correlated with allelic loss. Ninety percent (18/20) of the GIST patients in the high risk group showed LOH with at least one of the 9p21 markers, while 57.1% (8/14) in the intermediate risk group and 33.3% (5/15) in the very low and low risk groups, respectively (P < 0.05, χ 2 = 12.16). Eight (28.5%) of 31 patients with LOH and 1 (5.6%) of 18 patients without LOH died of the disease during the follow-up period. Loss of p16 protein expression occurred in 41.2%, but in 60% of the high risk group and 23.5% of the very low and low risk groups (P < 0.05, χ 2 = 4.98). p16 loss was associated with poor prognosis (P < 0.05, χ 2 = 4.18): the 3and 5-year overall survival rates were 84.8% and 70.8% for p16-negative and 100% and 92.0% for p16-positive patients, respectively. CONCLUSION: LOH at 9p21 appears to play an important role in GIST progression; decreased p16 expression in GIST is highly predictive of poor outcome.

Expression and prognostic role of molecular markers in 99 KIT-positive gastric stromal tumors in Taiwan Residents

AIM： TO elucidate the prognostic role and relationship of three molecular markers such as tumor suppressor gene p53, proliferating cell nuclear antigen （PCNA） and Ki-67 in gastric stromal tumor. METHODS： A total of 108 surgically resected gastric smooth muscle tumor specimens were collected from January 1987 to December 1999. Immunohistochemical studies were performed on the paraffin sections of 99 of 108 CDl17-positive tumors with antibodies of p53, PCNA, and Ki-67. Immunoreactivity of three molecular markers was recorded by labeling index （LI, %） and was analyzed for clinicopathologic and survival correlation. RESULTS： Of the 99 cases, immunostaining revealed that 52 patients （52.5%） had p53, and 37 patients （37.3%） had Ki-67 immunoreactivity （defined as 〉10% of LI）. All patients （100%） had PCNA immunoreactivity ranging from 12% to 93% of LI, divided into high or low by median. Statistics revealed that LI of three markers positively correlate to each other （P〈0.01） and to microscopic tumor mitotic counts （P〈0.001）. By combination, patients with ≥2 markers （positive or high） in tumors had early tumor recurrence （P〈0.001） and unfavorable outcome （P〈0.001）. Univariate analysis indicated that patients with tumor size 〉5 cm （P=0.003）, tumor mitosis 〉5/50 HPF （P〈0.001）, p53 immunoreactivity （P=0.001）, Ki-67 immunoreactivity （P=0.026）, high PCNA LI （P=0.015） and male gender （P=0.036） were six predictors for early disease recurrence. Subsequent multivariate analysis revealed that mitotic counts, tumor size, and p53 immunoreactivity were three independent prognostic factors for both disease free and overall survival of patients. By combination of three independent prognostic factors for grouping, we found higher tumor recurrence rate （P〈0.001） and shorter survival （P〈0.001） existed in groups with increasing factors. CONCLUSION： We first provide the prognostic value and linkage of three molecular markers in GISTs. The combination of three factors （p53, tumor size, and tumor mitosis） provides a more powerful prediction of prognosis than any single factor does.

Synchronous occurrence of gastric cancer and gastrointestinal stromal tumor: A case report and review of the literature

BACKGROUND To evaluate the clinicopathological features and prognosis of gastric cancer(GC)occurring synchronously with gastrointestinal stromal tumor(GIST).CASE SUMMARY We report 19 patients with concurrent GC and GIST(17 male and 2 female,median age 62 years).GC was most often located in the lower third of the stomach.GIST was diagnosed preoperatively in four patients.GIST was most often located in the gastric body(n=8,42%).The most common growth pattern in GIST was extraluminal(n=12,63%).The positive expression rates of CD117 and CD34 in GIST were 100% and 95%,respectively.Most patients with GIST(n=17,89%)were very low or low risk.There was no recurrence of GIST during follow-up.The 3-year cumulative survival rate was 73.9%,and the 5-year cumulative survival rate was 59.2%.The combined analysis of this study and literature reports(47 reports,157 patients)found that GC and GIST were usually located in the lower third(42%)and middle third(51%)of the stomach.GC was usually early(stage I:42%),poorly differentiated(42%)intestinal-type adenocarcinoma(51%).GISTs were primarily small in diameter(median:1.2 cm)and very low or low risk(89%).CONCLUSION Synchronous GC and GIST may not be rare.They have specific clinicopathological characteristics,and may have mutual inhibition in pathogenesis and progression.