Cholangiocarcinoma (CCA) is a heterogeneous group of tumours, derived from cells of the biliary tree, which represent the second most frequent primary liver tumour. According to the most recent ...classifications, CCA can be subdivided into intrahepatic (iCCA) and extrahepatic (eCCA) which include perihilar (pCCA) and distal (dCCA) CCA. CCA are usually identified at advanced stages, when the primary tumour grows enough to produce a large liver mass or when jaundice has developed because of biliary tree obstruction. The ongoing challenges in the identification of risk factors and definition of a specific population at higher risk of developing CCA are the main challenges for the development of screening programs. Therefore, late diagnosis remains an unresolved issue in CCA. Imaging plays an important role in the detection and characterization of CCA, helping with radiological diagnosis, guiding biopsy procedures and allowing staging of the tumour. This review focuses on clinical presentations and diagnosis and staging techniques of CCA.
Treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) or low-dose aspirin is associated with increased risk of upper gastrointestinal bleeding. There is little evidence on the risk of lower ...gastrointestinal bleeding with NSAIDs, antiplatelet agents (APAs), or anticoagulants. We aimed to quantify the relative risk (RR) of upper and lower gastrointestinal bleeding associated with use of NSAIDs, APAs, or anticoagulants.
We performed a case-control study that used data collected from consecutive patients hospitalized for gastrointestinal bleeding (563 upper, mean age, 63.6 ± 16.7 years and 415 lower, mean age, 70.8 ± 13.8 years), confirmed by endoscopy or other diagnostic procedures. Unhospitalized patients were used as controls (n = 1008) and matched for age, hospital, and month of admission. Drug use was considered current when taken within 7 days or less before hospitalization. RRs and 95% confidence intervals (CIs) were estimated by unconditional logistic regression analysis.
Use of anticoagulants, low-dose aspirin, and other drugs (non-aspirin-APA, 82.3% thienopiridines) was associated with upper and lower gastrointestinal bleeding; the risk was 2-fold higher for anticoagulants (RR, 4.2; 95% CI, 2.9-6.2) than for low-dose aspirin (RR, 2.1; 95% CI, 1.4-3.3) or other non-aspirin-APA drugs (RR, 2.0; 95% CI, 1.6-2.6). NSAID use was also associated with increased risk of gastrointestinal bleeding and greater for upper (RR, 2.6; 95% CI, 2.0-3.5) than lower gastrointestinal bleeding (RR, 1.4; 95% CI, 1.0-1.9). Use of proton pump inhibitors was associated with reduced risk of upper, but not lower, gastrointestinal bleeding.
Anticoagulants, low-dose aspirin, NSAIDs, and other non-aspirin-APA drugs are associated with increased risk of upper and lower gastrointestinal bleeding. Use of anticoagulants appears to be the strongest risk factor for gastrointestinal bleeding.
Mouse models of pancreatic cancer Herreros-Villanueva, Marta; Hijona, Elizabeth; Cosme, Angel ...
World journal of gastroenterology : WJG,
03/2012, Letnik:
18, Številka:
12
Journal Article
Odprti dostop
Pancreatic cancer is one of the most lethal of human malignancies ranking 4th among cancer-related death in the western world and in the United States, and potent therapeutic options are lacking. ...Although during the last few years there have been important advances in the understanding of the molecular events responsi- ble for the development of pancreatic cancer, currently specific mechanisms of treatment resistance remain poorly understood and new effective systemic drugs need to be developed and probed. In vivo models to study pancreatic cancer and approach this issue remain limited and present different molecular features that must be considered in the studies depending on the purpose to fit special research themes. In the last few years, several genetically engineered mouse models of pancreatic exocrine neoplasia have been developed. These models mimic the disease as they reproduce genetic alterations implicated in the progression of pancreatic cancer. Genetic alterations such as activating mutations in KRas, or TGFb and/or inactivation of tumoral suppressors such as p53, INK4A/ARF BRCA2 and Smad4 are the most common drivers to pancreatic carcinogenesis and have been used to create transgenic mice. These mouse models have a spectrum of pathologic changes, from pancreatic intraepithelial neo plasia to lesions that progress histologically culminating in fully invasive and metastatic disease and represent the most useful preclinical model system. These models can characterize the cellular and molecular pathology of pancreatic neoplasia and cancer and constitute the best tool to investigate new therapeutic approaches, chemopreventive and/or anticancer treatments. Here, we review and update the current mouse models that reproduce different stages of human pancreatic ductal adenocarcinoma and will have clinical relevance in fu- ture pancreatic cancer developments.
There is limited evidence to support the relationship between the consumption of animal-source foods other than red meat and processed meat and colorectal cancer (CRC) risk. We aimed to examine the ...recent available evidence from observational studies about the association between these food groups’ intake and CRC risk. For this systematic review, we searched the PubMed database for the last five years. A total of fourteen cohort studies and seven case−control studies comprising a total of >60,000 cases were included. The studies showed a consistent significant decrease in CRC risk, overall and by subsites, associated with a high consumption of total dairy products. Less strong effects associated with the consumption of any subtype of dairy product were observed. Fish consumption, overall and by subtypes (oily or non-oily and fresh or canned), showed a mild inverse association with CRC risk. The association between white meat and egg intake and CRC risk was low and based on a small number of studies; thus, these findings should be interpreted with caution. In conclusion, a high consumption of total dairy products was associated with a lower CRC risk. However, evidence for fish, white meat, and eggs and the CRC risk were not as strong.
Although colorectal cancer (CRC) is the most common cancer type in Lynch syndrome (LS) families, patients have also increased lifetime risk of other types of tumors. The accumulated risk of ...pancreatic cancer (PC) in LS patients is around 3.7% and developed tumors often present a characteristically medullary appearance with prominent lymphocytic infiltration. LS patients are considered in high risk for PC development as they present 8.6-fold increase compared with the general population. Here we review PC cases reported in LS patients and current management guidelines. Literature data show that LS is clearly associated with PC and recent publications also demonstrated a connection with pancreatic neoplasic precursor lesions such as intraductal papillary mucinous neoplasms (IPMN) in these patients. While screening techniques are well established for CRC detection, clear strategies are not yet uniform for PC. Magnetic resonance imaging (MRI) and/or endoscopic ultrasound every 1-2 years in MMR mutation carriers with PC in a first or second-degree relative is recommended. Better pancreatic cancer detection strategies should be urgently defined due to the importance of early diagnosis in this disease.
Background & Aims Circulating microRNAs (miRNAs/miRs) might be used as biomarkers for the diagnosis of cancer and other diseases. Noninvasive approaches are needed to complement and improve upon ...current strategies for colorectal cancer (CRC) screening. We investigated whether plasma levels of miRNA can differentiate patients with CRC from healthy individuals. We also investigated whether plasma samples from patients with premalignant neoplastic lesions, such as advanced adenomas (AAs), also had a different expression pattern of miRNAs. Methods We analyzed 196 plasma samples from 123 patients newly diagnosed with sporadic colorectal neoplasia (63 with CRC and 60 with AAs) and 73 healthy individuals (controls) seen at 2 tertiary medical centers in Spain. An initial set of samples was analyzed using a genome-wide miRNA expression profiling assay (n = 61). Quantitative reverse-transcription PCR was used to validate the expression of selected miRNAs in an independent cohort (n = 135). Results Patients with CRC or AAs had plasma miRNA expression profiles that differed significantly from those of controls. We selected a group of 13 miRNAs for validation in an independent cohort of patients; 6 (miR18a, miR19a, miR19b, miR15b, miR29a, and miR335) were confirmed to be significantly up-regulated in patients with CRC, differentiating patients with CRC from controls with area under the receiver operating characteristic curve values ranging from 0.80 (95% confidence interval CI, 0.71–0.89) to 0.70 (95% CI, 0.59–0.80). Only miR18a was confirmed to be significantly up-regulated in patients with AAs, compared with controls; the area under the receiver operating characteristic curve value was 0.64 (95% CI, 0.52–0.75). Conclusions Patients with CRC have significantly different patterns of miRNA expression than healthy individuals. These patterns might be developed as biomarkers for CRC, although they have limited value in identifying patients with premalignant neoplastic lesions.
Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease associated with autoimmune-related destruction of small to medium size intrahepatic bile ducts. The aetiology of PBC is ...unknown and its pathogenesis remains obscure. Both genetic variants and environmental factors have been linked to increased PBC susceptibility, with other alterations known to cooperate in disease pathobiology. Increasing evidence indicates the presence of epigenetic abnormalities in PBC, particularly alterations of cholangiocellular microRNAs (miRNAs or miRs). This review highlights and discusses the most relevant epigenetic alterations found in patients with PBC, focusing on the role of miR-506 in the promotion of cholestasis and immune activation.
This trial comparing colorectal-cancer mortality among patients screened with colonoscopy or fecal immunochemical testing (FIT) will be completed in 2021. As compared with FIT, colonoscopy detected a ...similar number of cancers but more adenomas on baseline screening.
Colorectal cancer is the third most common cancer worldwide and the second leading cause of cancer-related deaths.
1
Several studies have shown that colorectal-cancer screening is effective
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–
5
and cost-effective
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in the average-risk population.
Recommended strategies for colorectal-cancer screening fall into two broad categories: stool tests (occult blood and exfoliated DNA tests) and structural examinations (flexible sigmoidoscopy, colonoscopy, and computed tomographic colonography). Stool tests primarily detect cancer, and structural examinations detect both cancer and premalignant lesions.
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Stool tests for occult blood (guaiac testing and fecal immunochemical testing FIT) are predominantly used in Europe and Australia, whereas colonoscopy is the predominant screening . . .
Liver injury impacts hepatic inflammation in part via Toll-like receptor (TLR) signalling. Triggering receptor expressed on myeloid cells 2 (TREM-2) modulates TLR4-mediated inflammation in bone ...marrow (BM)-derived macrophages but its function in liver injury is unknown. Here we hypothesised that the anti-inflammatory effects of TREM-2 on TLR signalling may limit hepatic injury.
TREM-2 expression was analysed in livers of humans with various forms of liver injury compared with control individuals. Acute and chronic liver injury models were performed in wild type and
mice. Primary liver cells from both genotypes of mice were isolated for in vitro experiments.
TREM-2 was expressed on non-parenchymal hepatic cells and induced during liver injury in mice and man. Mice lacking TREM-2 exhibited heightened liver damage and inflammation during acute and repetitive carbon tetrachloride and acetaminophen (APAP) intoxication, the latter of which TREM-2 deficiency was remarkably associated with worsened survival. Liver damage in
mice following chronic injury and APAP challenge was associated with elevated hepatic lipid peroxidation and macrophage content. BM transplantation experiments and cellular reactive oxygen species assays revealed effects of TREM-2 in the context of chronic injury depended on both immune and resident TREM-2 expression. Consistent with effects of TREM-2 on inflammation-associated injury, primary hepatic macrophages and hepatic stellate cells lacking TREM-2 exhibited augmented TLR4-driven proinflammatory responses.
Our data indicate that by acting as a natural brake on inflammation during hepatocellular injury, TREM-2 is a critical regulator of diverse types of hepatotoxic injury.
Inflammatory bowel disease (IBD) is characterised by chronic inflammation of the gastrointestinal tract. Although its aetiology remains unknown, environmental and genetic factors are involved in its ...development. Regarding genetics, more than 200 loci have been associated with IBD but the transferability of those signals to the Basque population living in Northern Spain, a population with distinctive genetic background, remains unknown. We have analysed 5,411,568 SNPs in 498 IBD cases and 935 controls from the Basque population. We found 33 suggestive loci (p < 5 × 10
) in IBD and its subtypes, namely Crohn's Disease (CD) and Ulcerative Colitis (UC), detecting a genome-wide significant locus located in HLA region in patients with UC. Those loci contain previously associated genes with IBD (IL23R, JAK2 or HLA genes) and new genes that could be involved in its development (AGT, BZW2 or FSTL1). The overall genetic correlation between European populations and Basque population was high in IBD and CD, while in UC was lower. Finally, the use of genetic risk scores based on previous GWAS findings reached area under the curves > 0.68. In conclusion, we report on the genetic architecture of IBD in the Basque population, and explore the performance of European-descent genetic risk scores in this population.
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