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.

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.

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.

[Sonic hedgehog signaling enhanced the expression of histone demethylase, lysine-specific demethylase 8 in the head and neck squamous cell carcinoma cell line SCC-6].

OBJECTIVE: To determine whether the sonic hedgehog (Shh) signaling could regulate the expression of histone demethylases in the head and neck squamous cell carcinoma(SCC). METHODS: Human recombinant SHH-N protein or over-expression of the mutant 2 smoothened (M2-SMO) was applied to activate the Shh signaling in tongue squamous cell carcinoma cell line-SCC-6 in this study. Cyclopamine was used to block the Shh signaling in SCC-6. The real-time reverse transcription (RT)-PCR was used to detect the expression of histone demethylases at the mRNA level. RESULTS: The data showed that activation of the Shh signaling up-regulated the expression of histone demethylase, lysine-specific demethylase 8 (KDM-8) at the mRNA level by human recombinant SHH-N protein (1.841 ∼ 3.591 fold compare with untreated group; P < 0.01), over-expression of the M2-SMO also increased the expression of KDM-8 (1.358 ∼ 3.013 fold compared with empty vector group; P < 0.05), and after the Shh signaling was blocked by Cyclopamine, the expression of KDM-8 was down regulated (decreased 25.6% ∼ 66.6% compared with control cells, P < 0.05). CONCLUSIONS: Histone demethylase KDM-8 was downstream target gene of Shh signaling in head and neck squamous cell carcinoma cell line SCC-6, and its expression was positively regulated by the Shh signaling.