Background Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. Methods We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0•9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0•9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124.

Background and Aim : Colonic serrated lesions are premalignant lesions, using an alternative malignization pathway, including multiple genetic and epigenetic alterations, as: mismatch repair deficiency due to MutL homolog 1 ( MLH1 ) promoter methylation, tumor protein p53 ( TP53 ) mutations, activating mutations of v-Raf murine sarcoma viral oncogene homolog B ( BRAF ) and Kirsten rat sarcoma viral oncogene homolog ( KRAS ). Our study aims to evaluate MLH1, BRAF and p53 immunohistochemical (IHC) status in sessile serrated lesions (SSLs), with and without dysplasia. Materials and Methods : This is a retrospective case-control study including 20 SSLs with dysplasia and 20 SSLs without dysplasia (matching sex and age). IHC expression of MLH1, BRAF and p53 was evaluated as the percent of nuclear loss of MLH1, cytoplasmic positivity of BRAF and nuclear positivity of p53. Data concerning age, sex, localization of the lesion, dysplasia and IHC results were statistically processed using Microsoft Excel. Results : We had very polymorphous patterns of IHC expression for BRAF, MLH1 and p53, especially in the dysplastic group. Thus, two patients were BRAF+/MLH1-/p53+, three were BRAF+/MLH1-/p53-, one was BRAF+/MLH1+/p53- and six were BRAF+/MLH1+/p53+. Dysplastic lesions without BRAF mutation exhibited the following phenotype: one case BRAF-/MLH1-/p53+, four BRAF-/MLH1-/p53- and three BRAF-/MLH1+/p53+. In the control group (SSLs without dysplasia), there was a more homogenous distribution of cases: eight cases BRAF+/MLH1+/p53-, seven BRAF-/MLH1+/p53-, one BRAF-/MLH1-/p53+, two BRAF-/MLH1-/p53- and two BRAF-/MLH1+/p53+. Conclusions : There are more routes on the serrated pathway, with different mutations and time of acquisition of each genetic or epigenetic lesion with the same morphological result. These lesions should be stratified according to their risk to poor outcome and their need to further surveillance.

Undifferentiated carcinoma of the pancreas with osteoclast-like giant cells (UC-OGC) is a rare subtype of pancreatic cancer, accounting for less than 1% of all pancreatic tumors. Preoperative diagnosis is cumbersome as cross-sectional imaging is often not capable to distinguish between UCOGC and other pancreatic tumors such as pancreatic adenocarcinoma, mucinous carcinoma or neuroendocrine tumors and specific tumor markers seem to be lacking. Endoscopic ultrasound r `m(EUS) with tissue acquisition via fine-needle aspiration (FNA) or biopsy (FNB) with microscopic HE staining and immunohistochemistry allows for an accurate diagnosis, thus influencing further treatment. We present herein the cases of two patients with osteoclast-like giant cells tumors of the pancreas diagnosed by EUS-guided fine needle biopsy and perform a literature review on the role of EUS-guided biopsy for diagnosis.

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