Computed tomography radiogenomics: A potential tool for prediction of molecular subtypes in gastric stromal tumor.

BACKGROUND: Preoperative knowledge of mutational status of gastrointestinal stromal tumors (GISTs) is essential to guide the individualized precision therapy. AIM: To develop a combined model that integrates clinical and contrast-enhanced computed tomography (CE-CT) features to predict gastric GISTs with specific genetic mutations, namely KIT exon 11 mutations or KIT exon 11 codons 557-558 deletions. METHODS: A total of 231 GIST patients with definitive genetic phenotypes were divided into a training dataset and a validation dataset in a 7:3 ratio. The models were constructed using selected clinical features, conventional CT features, and radiomics features extracted from abdominal CE-CT images. Three models were developed: ModelCT sign, modelCT sign + rad, and model CTsign + rad + clinic. The diagnostic performance of these models was evaluated using receiver operating characteristic (ROC) curve analysis and the Delong test. RESULTS: The ROC analyses revealed that in the training cohort, the area under the curve (AUC) values for modelCT sign, modelCT sign + rad, and modelCT sign + rad + clinic for predicting KIT exon 11 mutation were 0.743, 0.818, and 0.915, respectively. In the validation cohort, the AUC values for the same models were 0.670, 0.781, and 0.811, respectively. For predicting KIT exon 11 codons 557-558 deletions, the AUC values in the training cohort were 0.667, 0.842, and 0.720 for modelCT sign, modelCT sign + rad, and modelCT sign + rad + clinic, respectively. In the validation cohort, the AUC values for the same models were 0.610, 0.782, and 0.795, respectively. Based on the decision curve analysis, it was determined that the modelCT sign + rad + clinic had clinical significance and utility. CONCLUSION: Our findings demonstrate that the combined modelCT sign + rad + clinic effectively distinguishes GISTs with KIT exon 11 mutation and KIT exon 11 codons 557-558 deletions. This combined model has the potential to be valuable in assessing the genotype of GISTs.

Gastrointestinal stromal tumor metastasis at the site of a totally implantable venous access port insertion: A rare case report.

BACKGROUND: The totally implantable venous access port (TIVAP) is an important device in patients for injecting blood products, parenteral nutrition or antineoplastic chemotherapy. Metastatic spread at the site of the insertion of a TIVAP is extremely rare. CASE SUMMARY: We report the case of 33-year-old male with advanced gastrointestinal stromal tumor (GIST) who underwent radical tumor resection after neoadjuvant imatinib therapy. However, a solitary GIST metastasis at the site of a TIVAP insertion developed during adjuvant imatinib treatment. Mutational analysis showed secondary mutation in KIT exon 13 (V564A), which is resistant to imatinib treatment. To our knowledge, this is the first case report of a patient with advanced GIST developing GIST metastasis at the site of a TIVAP insertion. CONCLUSION: This case highlights that when a patient with advanced, high metastatic GIST requires TIVAP insertion, we should realize that there is a risk of developing tumor metastasis at the site of a TIVAP insertion.

Prognoses in patients with primary gastrointestinal neuroendocrine neoplasms based on the proposed new classification scheme.

AIM: The aim of this study is to investigate the clinicopathological characteristics, as well as explore the prognostic accuracy of the proposed new classification in gastrointestinal NENs (GI-NENs) patients. METHODS: Patients diagnosed with GI-NENs were retrospectively indentified from existing databases of the pathological institute at our institution from January 2009 to November 2015. RESULTS: We identified 414 patients with GI-NENs, 250 cases were diagnosed as neuroendocrine tumor G1 (NET G1), 25 as neuroendocrine tumor G2 (NET G2), 53 as neuroendocrine tumor G3 (NET G3), 55 as neuroendocrine carcinoma G3 (NEC G3), and 31 as mixed adenoneuroendocrine carcinoma (MANEC); the overall survival (OS) rate at three years were 94.9%, 91.7%, 74.3%, 62.7% and 38.1%, respectively. The difference in progression-free survival (PFS) duration among the patients with NET G1, NET G2, NET G3, NEC G3, and MANEC was statistically significant (P < 0.001). However, the PFS of NEC G3 and MANEC was low and similar (P = 0.090). In multivariate analysis of patients with GI-NENs, surgical margin, comorbidity, proposed new classification and tumor location were useful predictors of OS (P < 0.05). CONCLUSION: Our findings suggest that the proposed new classification can accurately reflect the clinical outcome, together with surgical margin, comorbidity, and tumor location may be meaningful prognostic factors for the OS of GI-NENs.

[FAP Expression and Its Association with the Prognosis of Gastric Stromal Tumors].

OBJECTIVES: To determine the association of FAP expression with the prognosis of gastric stromal tumors (GSTs). METHODS: Paraffin-embedded GSTs samples were collected from January 2010 to December 2013 in the department of pathology of our hospital. FAP expression was examined by immunohistochemistry staining. Its correlations with clinical pathological characteristics and prognosis of GSTs were analyzed. RESULTS: A total of 98 cases were included in this study. FAP was expressed in the cytoplasm of GSTs cells, with a positive rate of 42.9%. No FAP expression was found in normal gastric tissues. No differences of FAP expression were found in patients with different gender, age and tumor mitotic counts (P >0.05). Tumor diameter and risk classification were associated with FAP expression (P <0.05). Higher levels of FAP expression were found in larger and higher risk tumors. No significant correlations between FAP expression and routine immunohistochemical markers were found. Log-rank univariate survival analysis showed that mitotic counts, tumor size, postoperative IM and FAP expression were associated with recurrence free survival of GSTs patients with intermediate-high risks (P <0.05). Cox multivariate survival analysis showed that mitotic counts, tumor size, postoperative IM and FAP were independent predictors for the prognosis of GSTs patients with intermediate-high risks (P <0.05). CONCLUSION: FAP is expressed in the cytoplasm of gastric GIST cells, but not in normal gastric tissues. FAP is a predictor for the prognosis of GSTs patients with intermediate-high risks.

[Associations of Preoperative Platelet-to-lymphocyte Ratio and Derived Neutrophil-to-lymphocyte Ratio with thePrognosis of Gastrointestinal Stromal Tumor].

OBJECTIVES: To determine the associations of preoperative platelet-to-lymphocyte ratio (PLR) and derived neutrophil-to-lymphocyte ratio (d-NLR) with the prognosis of gastrointestinal stromal tumor (GIST). METHODS: GIST patients with surgical treatment from June 2005 to February 2015 in West China Hospital of Sichuan University were enrolled in the study. The results of blood routine tests of the patients within one week prior to surgery and their clinical data were extracted. The patients were divided into high-PLR/d-NLR (PLR#>153.075, d-NLR#>1.245) and low-PLR/d-NLR (PLR≤153.075, d-NLR≤1.245) groups according to the optimal cutoff values of the receiver operating characteristic (ROC) curves. Recurrence-free survival (RFS) rates were calculated using Kaplan-Meier method. COX regression analyses were performed to identify factors associated with RFS for GIST patients without imatinib treatment. [WTHZ]. RESULTS: [WTBZ]Regardless of imatinib treatment, the patients with high PLR and d-NLR had shorter RFS than those with low PLR and d-NLR. Tumor diameter, location, mitotic counts, preoperative PLR and d-NLR were identified as factors associated with RFS in the univariate analyses. The multivariate analysis identified tumor diameter [≥5 cm, hazard ratio (HR): 4.295, 95% confidence interval (CI): 1.772-10.413, P=0.001], non-stomach (HR:2.247, 95%CI: 1.200-4.209; P=0.011), mitotic counts (>5/50 HPF: HR:4.678, 95%CI: 2.364-9.257; P<0.001) and high d-NLR (HR:2.549, 95%CI: 1.159-5.606; P=0.1020) as independent factors predicting the prognosis of GIST. The patients with high PLR or high d-NLR had shorter RFS than those with low PLR/d-NLR. [WTHZ]. CONCLUSION: [WTBZ]Preoperative d-NLR is an independent predictor of RFS in GIST. PLR and d-NLR can be used in predicting the recurrence risk of GIST.

[Characteristics of Clinicopathology and Genotype in 179 Cases with Gastrointestinal Stromal Tumor].

OBJECTIVE: To analyze the characteristics of the clinicopathology and genotypes in patients with gastrointestinal stromal tumor (GIST). METHODS: The clinicopathological and genotypic data of 179 patients with GIST, who underwent treatment and genetic testing in the Hostital of West China from September 2009 to February 2009 were collected retrospectively. RESULTS: The tumor sites of the cases were located in stomach (88 cases, 49.2%), small intestine (70 cases, 39.1%), colorectum (7 cases, 3.9%) and the other sites (14 cases, 7.8%) respectively. 94.4%, 74.9% and 93.3% of GIST patients were positive for CD117, CD34 and DOG-1 immunophenotypes respectively. C-kit and PDGFRα mutations were found in 151 cases (84.4%) and 8 cases (4.5%) except for the wild types of the rest 20 cases (11.2%). Among all the c-kit mutation, 92.2% mutation types in exon 11 were deletion mutation, point mutation and hybrid mutations, and in exon 9 the mutation types were just involving A502_Y503dup (n = 6) and Y403_F504ins (n = 14), while the mutation type were K642Q in exon 13 (n = 1) and N822K in 17 (n = 2). There were 6 patients with the mutation types of PDGFRα in exon 18, and 3 of them were type of D842V. In the GIST genotyping, DOG-1 positive rate in PDGFRα mutation patients were significantly lower than that in c-kit mutation and wild type patients (P = 0.007). In the various type of c-kit mutations, the positive rate of CD34 in point mutation patients were significantly lower than that in other mutation types (P < 0.001). The rate of high-risk patients in point mutation and insertion mutation patients were lower than that in deletion mutation and deletion + insertion mutation patients (P = 0.006). CONCLUSION: The most common localizaions of GISTs are the stomach and small intestine. The most frequent mutation type of GIST is c-kit exon 11. The individualized treatment is required for GIST patients because its high mutation rate and types.

[Quality of life of patients with gastric tube anastomosis after proximal gastrectomy in adenocarcinoma of esophagogastric junction].

OBJECTIVE: To compare postoperative quality of life (QOL) of patients receiving proximal gastrectomy (PG) for adenocarcinoma of gastroesophagealjunction (AEG) throughgastric tube anastomosis and traditional esophagogastrostomy. METHODS: Between January 2010 and February 2011, 112 patients were diagnosed as AEG in our hospital. All patients underwent curative operations. Two post-PG alimentary tract reconstruction methods were adopted: gastric tube anastomosis (n = 60) and traditional direct anastomosis (n = 52). The European Organization for Research and Treatment of Cancer (EORTC) Quality of life Questionnaire Core-30 (EORTC QLQ-C30) and QLQ-STO22 were used to assess QOL of those patients before and two years after operations. RESULTS: There were no statistically significant differences between the two groups of patients in clinical and pathologic characteristics, clinical pathological characteristics and preoperative QOL (P > 0.05). Two years after operations, the patients receiving traditional direct anastomosis showed higher scores in reflux, body image, and nausea and vomiting compared with those receiving gastric tube anastomosis. No statistical differences were found between the two groups of patients in general health, physical function, role function, fatigue and pain (P > 0.05). CONCLUSION: Gastric tube reconstruction could improve the postoperative QOL of AEG patients.

[Clinical analysis of efficacy and prognosis of intermediate risk gastric stromal tumor patients].

OBJECTIVE: To explore the clinical efficacy and prognosis of the patients with intermediate risk gastric stromal tumor (GST). METHODS: The data of intermediate risk GST patients confirmed by pathology and immunohistochemistry at Center of Gastrointestinal Surgery, West China Hospital, Sichuan University, between January 2007 and July 2011 were collected and retrospectively analyzed. And univariate and multivariate analyses were performed to assess the efficacy of imatinib mesylate (IM) according to recurrence-free survival (RFS). RESULTS: A total of 46 intermediate risk GST patients were enrolled with a median follow-up period of 31 (9-64) months. Among them, 20 patients received IM treatment and 1 had hepatic metastasis at 16 months after withdrawal. In contrast, 5 of 26 patients refusing IM treatment recurred or had a distant metastasis. The 1-, 2-, 3-year recurrence-free survival in IM treatment group and no IM treatment group were: 20/20 vs 25/26, 14/14 vs 17/20 and 6/7 vs 10/14, respectively. Cox proportion hazards regression: hazard ratio(HR) = 0.265, 95%CI: 0.025-2.761, P = 0.267. Among 6 patients with recurrence and(or) metastasis, 5 had mitotic count > 5/50 HPF. Cox proportion hazards regression (HR = 0.059, 95%CI: 0.004 - 0.976, P = 0.048) showed that IM can improve the progression free survival of mitotic count > 5/50 HPF group versus mitotic count < 5/50 HPF. The most common IM-related side effects were edema, nausea, abdominal discomfort, leukemia, etc. Most of them were Grade 1-2. CONCLUSIONS: Intermediate risk GST has a low rate of recurrence or metastasis. And 1-year IM treatment may improve the prognosis of the patients with mitotic counts > 5/50 HPF. Furthermore, IM treatment is safe in intermediate risk GST patients.

[Clinical research of the sentinel lymph node in patients with early gastric cancer].

OBJECTIVE: To assess the value of carbon nanoparticles which mapping sentinel lymph node (SLN) and predict the status of lymph node metastasis status in the early gastric cancer (EGC), and to explore the SLN distribution. METHODS: Forty five patients with EGC, who underwent surgical treatment, were enrolled. At the completion of exploratory laparotomy, 1 mL solution of carbon nanoparticles was injected subserosally in the gastric wall 4-6 sites around the primary tumor during surgery in all patients. The first stained lymph nodes were defined as the SLN. Postoperative SLN and dissection of the lymph node was sent for histopathological examination. RESULTS: Carbon nanoparticles were applied in 45 EGC patients for mapping SLN and 43 cases (95.6%) were observed with positive stain. 53 pieces of SLN were detected, average (1.23 +/- 0.53) pieces for one person. 11 of the 43 patients (25.6%) developed lymph node metastasis, through the SLN histopathological examination, 3 cases (7.0%) were false negative, the accuracy and sensitivity of the prediction of regional lymph node metastasis status was 93.0% and 72.7%, respectively. The false negative and negative predictive value was 27.3% and 91.4%. There were significant differences between the mucosal cancer group and submucous cancer group in the diameter of tumor (P = 0.042) and the rate of lymph node metastasis (P = 0.001). There were no significant differences between the two groups in the accuracy and sensitivity (P > 0.05). In 36 cases of gastric cancer patients, 23 SLN positive cases (63.9%) were detected in third group. CONCLUSIONS: The dyeing rate, accuracy and sensitivity of carbon nanoparticles mapping SLN for EGC were high. Carbon nanoparticles mapping SLN can more accurately predict perigastric lymph node metastasis status in patients with EGC.

[Prognostic analysis of 349 cases with gastrointestinal stromal tumor].

OBJECTIVE: To investigate the prognostic factors of gastrointestinal stromal tumor (GIST). METHODS: Clinical data of 349 cases of GIST patients in our hospital between January 2006 and September 2011 were analyzed retrospectively and the prognostic factors were evaluated. RESULTS: 335 patients underwent R0 resection and 14 with palliative resection. With a follow-up of 288 (82.5%) patients (median: 33 months, range 3-72 months), 61 patients with progressed were observed and 33 of them died. Unconditional logistic regression analysis showed that tumor location (P = 0.003, OR = 1.412, 95% CI: 1.125-1.772), risk classification (P = 0.011, OR = 2.930, 95% CI: 1.278-6.716) and use of imatinib treatment (P = 0.009, OR =0.291, 95 CI: 0.115-0.734) were independent factors for post-operative recurrence or metastasis. Survival analysis of 128 patients between January 2006 and December 2008, Cox regression analysis demonstrated diameter (P = 0.034, OR = 2.328, 95% CI: 1.065-5.089), risk classification (P = 0.015, OR = 3.031, 95% CI: 1.236-7.428) and use of imatinib treatment (P = 0.011, OR = 0.259, 95% CI: 0.091-0.734) were independent prognosis factors. CONCLUSIONS: No specific clinical manifestation was observed for GIST. Tumor location, diameter, risk classification and imatinib treatment could influence on prognosis. Radical resection combined with imatinib treatment could improve the prognosis.