Molecular Pathways of Carcinogenesis in Familial Adenomatous Polyposis.

Familial adenomatous polyposis (FAP) is a genetic syndrome characterized by the presence of multiple polyps in the gastrointestinal tract and a wide range of systemic extra-intestinal manifestations. Patients affected will inevitably undergo abdominal surgery due to the malignant transformation of one or more adenomas. The pathogenesis of the disease is based on a loss of function mutation in adenomatous polyposis coli (APC), a tumor-suppressor gene, inherited following a Mendelian pattern. This gene is a key component of multiple cell functions that cooperate for homeostasis; when mutated, it contributes to the progression of colorectal adenoma into cancer. Recent studies have demonstrated that several additional mechanisms may influence this process, such as alterations in gut microbiota composition and mucosal barrier immunity, interaction with the immune microenvironment and inflammation, the hormone estrogen, and other signaling pathways. These factors represent promising targets of future therapies and chemoprevention, aiming to alter the progressive nature of the disease and improve the quality of life of families affected. Therefore, we performed a narrative review about the current knowledge of the aforementioned pathways involved in colorectal cancer pathogenesis in FAP, exploring the genetic and environmental factors that may contribute to the development of CRC in FAP.

Comparison of Transient Elastography and Point Shear Wave Elastography for Analysis of Liver Stiffness: A Prospective Study.

Liver stiffness measurement (LSM) by Fibroscan is the most used non-invasive method to assess liver fibrosis. Recently, point-shear wave elastography (pSWE) has been introduced as a simple alternative non-invasive test. Therefore, we aimed to compare the results of these two techniques. One hundred and eighty-four consecutive patients attending our outpatient ultrasound clinic were recruited. LSM was performed by both Fibroscan and pSWE. Statistical analysis was conducted by Spearman's test for correlation and linear regression. Bland-Altman graphs and ROC curves were drawn with area under the curve (AUC). Overall, the correlation of LS between Fibroscan and pSWE was substantial (r = 0.68, p < 0.001). Linear regression showed a coefficient b= 0.94 ± 0.02. The Bland-Altman plot found a bias of -0.10, with only 11 values exceeding the 95% confidence interval. When only considering patients with a LSM of > 10 kPa (n = 31), we found an excellent r = 0.79 (0.60-0.90, p < 0.001). A cutoff of 12.15 kPa for pSWE had sensitivity = 74.2% and specificity = 99.3% to detect relevant fibrosis, with an AUC = 0.98. The highest correlation was observed for hepatitis C (r = 0.91) and alcoholic liver disease (ALD)(r = 0.99). In conclusion, pSWE shows LSM estimation in agreement with Fibroscan in most cases, and the best concordance was observed for hepatitis C and ALD, and for higher ranges of LS.