Irrigating Acetic Acid Solution During Colonoscopy for the Detection of Sessile Serrated Neoplasia: A Randomized Controlled Trial.

BACKGROUND: Misdiagnosed sessile serrated lesions (SSLs) are important precursors for interval colorectal cancers. AIMS: We investigated the usage of acetic acid (AA) solution for improving the detection of SSLs in the right colon in a randomized controlled trial. METHODS: A tandem observation of the right colon was performed in 412 consecutive patients. A first inspection was performed under white light high-definition endoscopy. In the AA group, a low concentration vinegar solution (AA: 0.005%) irrigated by a water pump in the right colon was compared with a plain solution of normal saline (NS) in the diagnostic yield of SSLs during the second inspection. Secondary outcomes in overall polyp detection were measured. RESULTS: Qualitative comparisons showed significant differences in the detection rates of all polyps except adenomas, with remarkable improvement in the demonstration of advanced (> 20 mm), SSLs, and hyperplastic polyps during the second inspection of the right colon using the AA solution. Significant improvement was also noted in the AA group, as far as the mean number of polyps/patient detected, not only in SSLs (AA group: 0.14 vs. NS group: 0.01, P < 0.001), but also in all histological types and all size-categories in the right colon. Small (≤ 9 mm) polyps were detected at a higher rate in the sigmoid colon expanding the effect of the method in the rest of the colon. CONCLUSION: AA-assisted colonoscopy led to a significant increase in SSLs detection rate in the right colon in a safe, quick, and effective manner.

The Effect of Early vs Delayed Initiation of Adalimumab on Remission Rates in Patients With Crohn's Disease With Poor Prognostic Factors: The MODIFY Study.

Background: Data on the effectiveness of anti-tumor necrosis factor medications in patients with Crohn's disease (CD) with poor prognostic factors (PPFs) are scarce. This study aimed to generate real-world evidence on the effect of early (≤24 months after diagnosis) vs delayed (>24 months) initiation of adalimumab (ADL) on the 26-week remission rate (Harvey-Bradshaw Index ≤4) in these patients. Methods: This multicentre, retrospective, chart review study performed in 10 Greek hospitals enrolled adult patients with moderate to severe CD (Harvey-Bradshaw Index ≥8) with ≥3 PPFs who were initiated on ADL ≥12 months before enrollment. A sample size of 164 patients (early:delayed cohort allocation ratio, 30:70) was required to address the primary endpoint. Results: Eligible patients (n = 171) were consecutively enrolled. In the early vs delayed cohorts, the 26-week remission rates (off-steroids) using the last-observation-carried-forward imputation method were 60.7% (37/61) vs 47.2% (50/106), respectively (Δ = 13.5%, P = .044). The respective remission rates were 61.2% vs 42.4% among anti-tumor necrosis factor-naive patients (P = .023) and 58.3% vs 53.2% among anti-tumor necrosis factor-experienced patients (P = .374). The 52-week remission rates using as-observed data were 78.8% and 60.3%, and the intestinal resection rates were 6.5% and 11.9% in the early vs delayed ADL cohorts, respectively. Conclusions: Patients with CD with PPFs who received early vs delayed treatment with ADL achieved higher clinical response and remission rates. This effect was more pronounced in those patients who were bio-naive and steroid-dependent/refractory with concurrent extraintestinal manifestations than those who were not.

Long non-coding RNA in pancreatic adenocarcinoma and pancreatic neuroendocrine tumors.

Interest in non-coding regions of DNA has been increasing since the mapping of the human genome revealed that human DNA contains far fewer genes encoding proteins than previously expected. However, analysis of the derivatives of DNA transcription (transcriptomics) revealed that the majority of the genetic material is transcribed into non-coding RNA (ncRNA), indicating that these molecules probably provide the functional diversity and complexity of the physiology of the human body that cannot be attributed to the proteins. Of these ncRNA, long ncRNA (lncRNA) have a length greater than 200 nucleotides and share many common components with the coding messenger RNA (mRNA): They are transcribed by RNA polymerase II, comprised of multiple exons and subjected to normal RNA splicing giving RNA products of several kilobases. Scientific data reveal the regulatory role of lncRNA in the control of gene expression during cell development and homeostasis. However, to date, very few lncRNAs have been characterized in depth, and lncRNAs are thought to have a wide range of functions in cellular and developmental processes. These molecules will have the possibility to be used as biomarkers and contribute to the development of targeted therapies. Concerning pancreatic cancer, there are limited data in the literature that correlate the growth of these tumors with deregulation of various lncRNA. We herein review the literature regarding the role of lncRNA as a diagnostic and prognostic biomarker and possible therapeutic target in the neoplasms of the pancreas, particularly pancreatic adenocarcinoma and pancreatic neuroendocrine tumors.

Mucins in neoplasms of pancreas, ampulla of Vater and biliary system.

Tumors of the pancreas, the ampulla of Vater, and the extrahepatic and intrahepatic bile ducts have significant histological similarities due to the common embryonic origin of the pancreatobiliary system. This obviates the need for discovery of biomarkers with diagnostic and prognostic value for these tumors. Mucins, especially MUC-1, -2, -4 and -5AC, are important candidates for developing into such reliable biomarkers. Increased expression of MUC1 occurs in pancreatic ductal adenocarcinomas and is associated with increased degrees of dysplasia in pancreatic intraepithelial neoplasia (PanIN). Positive expression of MUC2 in intraductal papillary mucinus neoplasms (IPMN) of the intestinal type indicates high potential progression to invasive carcinoma with de novo expression of MUC1, while absence of MUC2 expression in IPMNs of gastric type implies low potential to malignant evolution. De novo MUC4 expression correlates to the severity of dysplasia in PanIN and is associated with a poor prognosis in patients with pancreatic ductal adenocarcinomas. In biliary intraepithelial neoplasia (BilIN), increased expression of MUC1 is associated with higher degrees of dysplasia. Intrahepatic cholangiocarcinomas (ICC) are characterized by increased expression of all glycoforms of MUC1. Positive MUC2 expression in intraductal papillary neoplasm of the bile ducts (IPNB) of the intestinal type indicates high malignant potential with de novo expression of MUC1 in the invasive element. Absent MUC2 expression in any degree of BilIN may prove useful in differentiating them from IPNB. De novo expression of MUC4 is associated with poor prognosis in patients with ICC or carcinoma of the extrahepatic bile ducts (EHBDC). High de novo expression of MUC5AC is found in all degrees of BilIN and all types of IPNB and ICC. The MUC5AC is useful in the detection of neoplastic lesions of the bile duct at an early stage. Increased expression of mucin MUC1 in carcinoma of the ampulla of Vater associated with unfavorable behavior of the tumor, such as lymph node metastasis, infiltration of the pancreas and duodenum, advanced TNM classification and worse prognosis. Patients with intra-ampullary papillary-tubular neoplasm (IAPN) of the pancreatobiliary immunophenotype did not show MUC2, while those of the intestinal immunophenotype are MUC2 positive. The expression of MUC4 is associated with poor prognosis in patients with carcinoma of the ampulla of Vater favoring metastasis and making them resistant to apoptosis. Moreover, it appears that MUC4 positivity correlates with recurrence of the tumor. Expression of MUC5AC is associated with the invasive potential of the tumor.