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This study aimed to evaluate the clinical and prognostic characteristics of primary gastric gastrointestinal stromal tumors (GIST). Patients who underwent resection for primary gastric GIST between January 2002 and December 2017 were included. Recurrence-free survival (RFS) was calculated by Kaplan–Meier analysis, and Cox proportional hazards model was used to identify independent prognostic factors. Altogether, 653 patients were enrolled. The median patient age was 59 years (range 15-86 years). Open, laparoscopic, and endoscopic resections were performed in 394 (60.3%), 105 (16.1%), and 154 (23.6%) patients, respectively. According to the modified NIH consensus classification, 132 (20.2%), 245 (37.5%), 166 (25.4%), and 88 (13.5%) patients were categorized into very low-, low-, intermediate-, and high-risk, respectively. A total of 136 (20.8%) patients received adjuvant imatinib treatment. The median follow-up time was 78 months (range 4–219 months), and the estimated 5-year RFS rate was 93.0%. In all patients, tumor size and rupture, mitotic counts, and adjuvant imatinib treatment were independent prognostic factors. The prognosis of gastric GIST treated with endoscopic resection was not significantly different from that of laparoscopic or open resection after adjusting for covariates using propensity score matching (log-rank p =.558). Adjuvant imatinib treatment (HR = 0.151, 95%CI 0.055–0.417, p <.001) was a favorable prognostic factor for high-risk patients, but was not associated with prognosis in intermediate-risk patients. Patients with small gastric GISTs who successfully underwent endoscopic resection may have a favorable prognosis. Adjuvant imatinib treatment improve the prognosis of high-risk gastric GISTs, however, its use in intermediate-risk patients remains controversial. [ABSTRACT FROM AUTHOR]

The modified National Institutes of Health (NIH) risk criteria for gastrointestinal stromal tumours (GISTs) have some limitations and need to be improved. Patients who underwent radical resection of primary GIST were retrospectively reviewed. Peripheral blood indices including the neutrophil-to-lymphocyte ratio (NLR) and prognostic nutritional index (PNI) were analysed. Recurrence-free survival (RFS) was calculated and compared. Multivariate analysis was conducted. Area under the receiver operating characteristic curve (ROC) was calculated. A total of 492 patients were enrolled. Tumour size, mitotic index (MI), tumour location and PNI were independent prognostic factors. The modified NIH criteria could not distinguish among very low-, low- and intermediate-risk patients, and PNI was the only independent prognostic factors for them. The five-year RFS rate in the high risk (HR) group was significantly lower. A further modification to the NIH risk criteria was proposed (the 'NIH-PNI stratification'). Non-high risk (NHR) patients were divided into the NHR-PNI-H group (PNI > 48.05) and the NHR-PNI-L group (PNI ≤ 48.05), respectively. HR patients were divided according to tumour size and MI: the HR1, HR2 and HR3 groups. The five-year RFS rates of the NHR-PNI-H, NHR-PNI-L, HR1, HR2 and HR3 groups were 97.3%, 93.5%, 74.1%, 61.7% and 24.4%, respectively (p <.001). The area under the curve (AUC) for the NIH-PNI stratification, modified NIH criteria, NIH criteria (2002), AFIP criteria and nomogram were 0.857, 0.807, 0.817, 0.843 and 0.831, respectively. The proposed NIH-PNI stratification was able to distinguish among five groups in terms of risk of recurrence. A further modification to the NIH risk criteria for GISTs was proposed ('NIH-PNI stratification'). Non-high risk (NHR) patients were divided into NHR-PNI-H and NHR-PNI-L groups. High risk (HR) patients were divided to HR1, HR2 and HR3 groups. The five-year RFS rates were 97.3%, 93.5%, 74.1%, 61.7% and 24.4%, respectively (p <.001). The AUC for the NIH-PNI stratification, modified NIH criteria, NIH criteria (2002), AFIP criteria and nomogram were 0.857, 0.807, 0.817, 0.843 and 0.831. [ABSTRACT FROM AUTHOR]

Mitophagy is a key intracellular process that selectively removes damaged mitochondria to prevent their accumulation that can cause neuronal degeneration. During mitophagy, PINK1 (PTEN induced kinase 1), a serine/threonine kinase, works with PRKN/parkin, an E3 ubiquitin ligase, to target damaged mitochondria to the lysosome for degradation. Mutations in the PINK1 and PRKN genes cause early-onset Parkinson disease that is also associated with mitochondrial dysfunction. There are a large number of reports indicating the critical role of PINK1 in mitophagy. However, most of these findings were obtained from in vitro experiments with exogenous PINK1 expression and acute damage of mitochondria by toxins. Recent studies using novel animal models suggest that PINK1-PRKN can also function independent of mitochondria. In this review, we highlight the major differences between in vitro and in vivo models for investigating PINK1 and discuss the potential mechanisms underlying these differences with the aim of understanding how PINK1 functions under different circumstances.Abbreviations: AAV: adeno-associated viruses;AD: Alzheimer disease; CCCP: carbonyl cyanidem-chlorophenyl hydrazone; HD: Huntington disease; MPTP: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; MTS: mitochondrial targeting sequence; PD: Parkinson diseases; PINK1: PTEN induced kinase 1; PRKN: parkin RBR E3 ubiquitin protein ligase; ROS: reactive oxygen species; UIM, ubiquitin interacting motif. [ABSTRACT FROM AUTHOR]

Aim: The majority of available data on the clinical efficacy of sunitinib in patients with imatinib-resistant or -intolerant gastrointestinal stromal tumours (GISTs) are from studies of western populations. We investigated the clinical outcomes of imatinib dose escalation versus sunitinib in first-line imatinib-failure Asian GIST patients to further guide clinical treatment. Methods: Patients received imatinib dose escalation and a shift to sunitinib (Group A) or a direct shift to sunitinib (Group B). The objective tumour response was assessed according to Choi's criteria. Progression-free survival (PFS) and overall survival (OS) were calculated. The relationship between genetic mutation and survival was analysed. Results: In total, 40 patients who fulfilled the inclusion criteria were recruited. The differences in survival between Group A and Group B were not significant for PFS (p = .776) or OS (p = .219). For patients with KIT exon 11 mutation, a trend towards a better PFS was found in Group B (p = .122), OS of Group B was better than Group A (p = .013). The median PFS and OS of sunitinib treatment were 8 and 24 months, respectively, and a clinical benefit was observed in 80%. Patients with KIT exon 11 mutations had better PFS compared to those with KIT exon 9 mutations or wild-type GISTs (p = .017, p = .040, respectively). Conclusions: Both imatinib dose escalation and sunitinib were optional in Asian patients after failure of first-line imatinib, and patients with KIT exon 11 mutation benefited more from a direct shift to sunitinib. [ABSTRACT FROM AUTHOR]