Acute pancreatitis (AP) is a severe inflammation of the pancreas presented with sudden onset and severe abdominal pain with a high morbidity and mortality rate, if accompanied by severe local and systemic complications. Numerous studies have been published about the pathogenesis of AP; however, the precise mechanism behind this pathology remains unclear. Extensive research conducted over the last decades has demonstrated that the first 24 h after symptom onset are critical for the identification of patients who are at risk of developing complications or death. The identification of these subgroups of patients is crucial in order to start an aggressive approach to prevent mortality. In this sense and to avoid unnecessary overtreatment, thereby reducing the financial implications, the proper identification of mild disease is also important and necessary. A large number of multifactorial scoring systems and biochemical markers are described to predict the severity. Despite recent progress in understanding the pathophysiology of AP, more research is needed to enable a faster and more accurate prediction of severe AP. This review provides an overview of the available multifactorial scoring systems and biochemical markers for predicting severe AP with a special focus on their advantages and limitations.

Gastrointestinal stromal tumours (GISTs) are rare mesenchymal tumours of the digestive tract and are commonly driven by oncogenic mutations in KIT and PDGFRA genes. Tumour size, location, mitotic index and KIT/PDGFRA mutations are the most important prognostic parameters in GISTs. However, additional studies screening for new molecular prognostic markers in GISTs are missing. Raf kinase inhibitor protein (RKIP) has been considered as a suppressor of metastasis and a prognostic marker in several neoplasms. In the present study we aimed to examine whether RKIP expression is associated with GIST clinical-pathological features. Using immunohistochemistry, we determined RKIP expression levels in a well-characterised series of 70 GISTs. We found that RKIP is expressed in the great majority of cases, and absent in approximately 9% of GISTs. Additionally, we found that loss of RKIP expression was not due to the promoter methylation as assessed by methylation-specific PCR. Loss of RKIP expression was associated with poor disease-specific survival and with tumour necrosis in GISTs. Furthermore, a statistical tendency was observed between the positive RKIP expression and absence of metastasis. So far, this is the first study assessing RKIP expression levels in GISTs. We conclude that loss of RKIP expression could have an important role as prognostic marker in GISTs.

High risk and positive macroscopic surgical margin status are parameters associated with poor disease-specific survival in GIST patients.

Aim: To assess KIT and PDGFRA mutations frequencies in a Portuguese series of gastrointestinal stromal tumours (GISTs). Methods: 78 GISTs were evaluated for CD117 expression and screened for mutations in KIT (exons 9, 11, 13, 14 and 17) and PDGFRA (exons 12, 14 and 18) genes. Results: KIT activating mutations were identified in 44 (56%) of the 78 GISTs. Forty cases (91%) presented a mutation in KIT exon 11, and 4 (9%) in exon 9. One case showed a 4 bp deletion in intron 14. PDGFRA mutations were observed in 5 cases (6%): 2 (3%) in exon 12 and 3 (4%) in exon 18. Survival analysis was performed in 63 of the 78 GISTs. The presence of mutated KIT was significantly correlated with shorter survival of patients (p = 0.0460), and inversely associated with epithelioid histological type of GISTs (p = 0.0064). Conclusions: Overall, the incidence of both KIT and PDGFRA mutations in these Portuguese series was 63%, being in agreement with other studies, mainly of Iberian populations. The great majority of mutations were located in KIT exon 11, statistically associated with worse prognosis and indicative of favourable response to imatinib-based therapy in this Portuguese series of GISTs.

Somatic mutations in the promoter region of telomerase reverse transcriptase (TERT) gene, mainly at positions c. − 124 and c. − 146 bp, are frequent in several human cancers; yet its presence in gastrointestinal stromal tumor (GIST) has not been reported to date. Herein, we searched for the presence and clinicopathological association of TERT promoter mutations in genomic DNA from 130 bona fide GISTs. We found TERT promoter mutations in 3.8% (5/130) of GISTs. The c. − 124C4T mutation was the most common event, present in 2.3% (3/130), and the c. − 146C4T mutation in 1.5% (2/130) of GISTs. No significant association was observed between TERT promoter mutation and patient's clinicopathological features. The present study establishes the low frequency (4%) of TERT promoter mutations in GISTs. Further studies are required to confirm our findings and to elucidate the hypothetical biological and clinical impact of TERT promoter mutation in GIST pathogenesis.

In the absence of RAS mutations, MAPK could be activated through SCF/KIT autocrine/paracrine mechanisms and/or mutated BRAF in a subset of KIT/PDGFRA wild-type GISTs.

Acute pancreatitis (AP) is an inflammatory disorder of the pancreas that, when classified as severe, is associated with high morbidity and mortality. Promptly identifying the severity of AP is of extreme importance for improving clinical outcomes. The aim of this study was to compare the prognostic value of serological biomarkers, ratios, and multifactorial scores in patients with acute biliary pancreatitis and to identify the best predictors. In this observational and prospective study, the biomarkers, ratios and multifactorial scores were evaluated on admission and at 48 h of the symptom onset. On admission, regarding the AP severity, the white blood count (WBC) and neutrophil–lymphocyte ratio (NLR), and regarding the mortality, the WBC and the modified Marshall score (MMS) showed the best predictive values. At 48 h, regarding the AP severity, the hepcidin, NLR, systemic inflammatory response index (SIRI) and MMS and regarding the mortality, the NLR, hepcidin and the bedside index for severity in AP (BISAP) score, showed the best predictive values. The present study enabled the identification, for the first time, of SIRI as a new prognostic tool for AP severity, and validated hepcidin and the NLR as better prognostic markers than C-reactive protein (CRP) at 48 h of symptom onset.

Acute pancreatitis (AP) is a severe disease associated with high morbidity and mortality. Clinical studies can provide some data concerning the etiology, pathophysiology, and outcomes of this disease. However, the study of early events and new targeted therapies cannot be performed on humans due to ethical reasons. Experimental murine models can be used in the understanding of the pancreatic inflammation, because they are able to closely mimic the main features of human AP, namely their histologic glandular changes and distant organ failure. These models continue to be important research tools for the reproduction of the etiological, environmental, and genetic factors associated with the pathogenesis of this inflammatory pathology and the exploration of novel therapeutic options. This review provides an overview of several murine models of AP. Furthermore, special focus is made on the most frequently carried out models, the protocols used, and their advantages and limitations. Finally, examples are provided of the use of these models to improve knowledge of the mechanisms involved in the pathogenesis, identify new biomarkers of severity, and develop new targeted therapies.