Association Between the Nutritional Risk and the Survival Rate in Newly Diagnosed GIST Patients

Background: Currently, the incidence of gastrointestinal stromal tumors (GIST) is increasing rapidly worldwide. Malnutrition may increase the risk of perioperative complications and affect the prognosis of patients. However, previous studies on the nutritional status of GIST patients and its impact on prognosis are limited. Therefore, this study aims to explore the incidence of malnutrition in newly diagnosed GIST patients, the proportion of participants in need of nutritional intervention, and the relationship between nutritional status and overall survival (OS).Methods: We retrospectively analyzed the clinical data of GIST patients treated in our hospital from January 2014 to January 2018. Nutritional Risk Screening 2002 (NRS2002) and Patient-Generated Subjective Global Assessment (PG-SGA) were used to assess the nutritional status of all patients. This study was to investigate the clinical significance of PG-SGA by analyzing the relationship between PG-SGA score and OS.Results: A total of 1,268 newly diagnosed GIST patients were included in this study, of which 77.76% were at risk of malnutrition (NRS2002 score ≥ 3), and the incidence of malnutrition was 10.09% (PG-SGA score ≥ 4). Meanwhile, we found 2.29% of the patients required urgent nutritional support (PG-SGA score ≥ 9). Multivariate analysis showed that age (p = 0.013), BMI (p = 0.001), weight loss (p = 0.001), anemia (p = 0.005), pre-albumin (p = 0.010), albumin (p = 0.002), tumor location (p = 0.001), tumor size (p = 0.002), and NIH classification (p = 0.001) were risk factors for nutritional status. The prognosis was significantly in GIST patients with different PG-SGA score at admission (p < 0.05).Conclusion: This study suggested that malnutrition is common in newly diagnosed GIST patients, and the higher the PG-SGA score, the worse the clinical outcome.

Breakthrough COVID-19 infection rate with Indian strain in Single-center Healthcare Workers: A real world data.

Introduction: It is observed that many healthcare workers got COVID19 infection despite of completing both doses of Covishield vaccine. This study aimed to find real incidence of vaccine breakthrough infection. Material and methods: All hospital employees, who were fully vaccinated were included in study. Details about their vaccine side effects, infection prior to vaccination, post vaccination infection, severity of infection, hospital and ICU admission were noted. Results: None encountered any significant side effects of vaccine. Of the 461 participants, 86 (18.65%) got infection average 38 days (range 14 to 70days) after vaccination. As per the NIH classification, out of 86, disease was mild in 69(80.2%), moderate in 10(11.62%), severe in 6(6.97%) and critical in 1(1.16%). Of these, 10(11.62%) required hospital admission. Of these 10, 2 were shifted to ICU. Of the 2, One recovered while one died. Thus mortality was 1/86(1.6%). Conclusion: Breakthrough infection rate in health care workers was 18.65%. Moderate, severe or critical disease occurred in 19.7% participants even after two doses of vaccine. Mortality due to disease cannot be completely obviated due to vaccine. The vaccine was safe without any significant adverse events.

Quantitative proteomic analysis of aberrant expressed lysine acetylation in gastrointestinal stromal tumors

Background Gastrointestinal stromal tumor (GIST) is a common digestive tract tumor with high rate of metastasis and recurrence. Currently, we understand the genome, transcriptome and proteome in GIST. However, posttranscriptional modification features in GIST remain unclear. In the present study, we aimed to construct a complete profile of acetylome in GIST. Methods Five common protein modifications, including acetylation, succinylation, crotonylation, 2-hydroxyisobutyrylation, and malonylation were tested among GIST subgroups and significantly differentially- expressed lysine acetylation was found. The acetylated peptides labeled with Tandem Mass Tag (TMT)under high sensitive mass spectrometry, and some proteins with acetylation sites were identified. Subsequently, these proteins and peptides were classified into high/moderate (H/M) risk and low (L) risk groups according to the modified NIH classification standard. Furthermore, cell components, molecular function, biological processes, KEGG pathways and protein interaction networks were analyzed. Results A total of 2904 acetylation sites from 1319 proteins were identified, of which quantitative information of 2548 sites from 1169 proteins was obtained. Finally, the differentially-expressed lysine acetylation sites were assessed and we found that 42 acetylated sites of 38 proteins were upregulated in the H/M risk group compared with the L risk group, while 48 acetylated sites of 44 proteins were downregulated, of which Ki67 K1063Ac and FCHSD2 K24Ac were the two acetylated proteins that were most changed. Conclusions Our novel findings provide further understanding of acetylome in GIST and might demonstrate the possibility in the acetylation targeted diagnosis and therapy of GIST.

Clinicopathological characteristics and outcomes of gastrointestinal stromal tumors with high progranulin expression

Background & aims Progranulin (PGRN) is known to promote tumorigenesis and proliferation of several types of cancer cells. However, little is known about the clinicopathological features of patients with gastrointestinal stromal tumors (GISTs) with regard to PGRN expression. Methods A retrospective analysis was performed on patients with GISTs who underwent curative surgical resection between 2007 and 2017. PGRN expression was evaluated by immunohistochemical (IHC) analysis and semi-quantitatively categorized (no expression, 0; weak, 1+; moderate, 2+; strong, 3+). Tumors with a staining intensity of 2+ or 3+ were considered high PGRN expression. Results Fifty-four patients were analyzed; 31 patients (57%) were male. The median age at surgery was 60 years (range, 33–79), and the most common primary site was the stomach (67%). Thirty-five patients (65%) had spindle histology; 42 patients (78%) were separated as a high-risk group according to the modified National Institutes of Health (NIH) classification. High PGRN-expressing tumors were observed in 27 patients (50%), had more epithelioid/mixed histology (68% vs. 32%; p = 0.046), and KIT exon 11 mutations (76% vs. 24%; p = 0.037). Patients with high PGRN-expressing tumors had a worse recurrence-free survival (RFS) (36% of 5-year RFS) compared to those with low PGRN-expressing tumors (96%; p<0.001). Multivariate analysis showed that high PGRN expression and old age (>60 years) were independent prognostic factors for poor RFS. Conclusions High PGRN-expressing GISTs showed more epithelioid/mixed histology and KIT exon 11 mutations. PGRN overexpression was significantly associated with poor RFS in patients with GISTs who underwent curative resection.

Ikaros Expression in the Graft Is Associated with Chronic Graft Versus Host Disease

Introduction: Hematopoietic stem cell transplantation (HSCT) is the only potentially curative treatment for several diseases. Immune reconstitution post HSCT is a complex and extremely variable process. Ikaros transcription factor has an important role in hematopoiesis of several cell lines, especially in the lymphoid compartment. We hypothesized that Ikaros expression, both in the graft and in the recipient after transplant, might influence immune reconstitution and, consequently, the risk of opportunistic infections, relapse, and graft versus host disease (GVHD). Objectives: To correlate Ikaros expression both in the graft and in the recipient's peripheral blood (PB) after engraftment with the risk of GVHD after allogeneic HSCT outcomes. Patients and methods: 51 patients were included. Median age was 51 years (19-80), 53% of patients were male, and 57% of them had acute leukemia. Donor were haploidentical in 45% of cases, related identical in 29% and unrelated identical in 26%. Most patients (82%) received reduced-intensity conditioning regimens. Median follow-up was 20 months (10-40 months). Samples were collected from the graft and from the PB of the recipient 3 weeks after neutrophil recovery. Real time polymerase chain reaction (RT-PCR) was performed for analysis of absolute and relative Ikaros expression. Results: There was no association between Ikaros expression and the risk of acute GVHD, relapse or mortality. However, a significant association was observed in the risk of chronic GVHD. Cumulative incidence (CI) of chronic GVHD and of moderate / severe chronic GVHD (according to National Institute of Health - NIH classification) in two years were 49% and 28%, respectively. Higher Ikaros expression in the graft was associated with a significantly higher risk of moderate/severe chronic GVHD (54% vs. 15%, respectively, P=0.01). Higher Ikaros expression in the recipient's PB after engraftment was also associated with a significantly higher risk of moderate/severe chronic GVHD (65% vs. 11%, respectively, P=0.01). Conclusions: Ikaros expression in the graft and in the PB of the recipient after transplant seems to be correlated with a higher risk of moderate/severe chronic GVHD and might be evaluated in larger and prospective trials as a potential biomarker. Disclosures No relevant conflicts of interest to declare.

Gastrointestinal Stromal Tumors Etiology, Clinical Presentation And Review Of The Literature In Greek Patients

Gastrointestinal stromal tumors (GIST) represent rare malignancies of mesenchymal origin that can appear at any site of the gastrointestinal tract. Their classification, patient treatment and prognosis had been a source of controversy. The biology of these tumors revealed association to the type III tyrosine kinase receptor and the KIT CD117 protein expression. GIST mesenchymal lesions derive from the interstitial cells of Cajal. Classification methods include the one by Miettinen and Lasota and the ‘‘modified NIH classification’’. The treatment of choice is surgical intervention and complete removal of the neoplasm. In patients with tumors that cannot be excised, have given metastasis, or are of high risk for metastasis, treatment also involves Kit/PDGFRA tyrosine kinase inhibitors, such as imatinib. In Greece, several cases have been described.

Tumor-infiltrating immune cells signature predicts recurrence free survival after complete resection of localized primary gastrointestinal stromal tumors

BackgroundGrowing evidence has proposed prognostic value of immune infiltration in gastrointestinal stromal tumors (GISTs). Therefore, we aimed to develop a novel immune-based prognostic classifier (IPC) to help better stratify and predict prognosis of GISTs.MethodsThe gene expression profiles of 22 immune features of GISTs were detected from GEO dataset. The IPC was constructed using the LASSO Cox regression model and validated in a cohort including 54 patients with complete resection of localized primary GISTs via immunohistochemistry process. The performance assessment of the IPC was estimated, then compared with conventional risk prognostic criteria.ResultsThe IPC was established based on 4 features: CD8, CD8/CD3, CD68, CD163/CD68 and validated to be an independent predictor of RFS for GISTs (HR 5.2, 95%CI 1.99-13.65). Significant differences were found between low- and high-IPC group in 5-year RFS (92.6% vs 48.1%, p < 0.001). Using the IPC, the high-risk group of the Modified NIH classification was split into two groups in 5-year RFS (low-IPC vs high-IPC, 85.7% vs 30.0%, p < 0.001). The IPC showed a higher net benefit than both “treat all” or “treat none” methods for the threshold probability within a range of 0-0.62 and exhibited a performance (AUC 0.842) superior to modified NIH classification (AUC 0.763).ConclusionThe IPC was effective to predict RFS after complete resection of localized primary GISTs, adding prognostic value to the routine clinical prognostic criteria. Prospective studies are needed to further validate the analytical accuracy and practicability of the IPC in estimating prognosis of GISTs.