Successful Non-Invasive treatment of stricturing fibrosing colonopathy in an adult patient

<p>Abstract</p> <p>Objective</p> <p>Fibrosing colonopathy (FC) is a rare entity associated with cystic fibrosis (CF). Until now, patients with stricturing FC have usually been treated surgically. In this instance, we aimed at avoiding surgery by applying a new conservative approach.</p> <p>Methods</p> <p>Case report on an adult with CF who developed persistent abdominal pain due to a non-passable stricture in the right transverse colon. Histology confirmed fibrosing colonopathy.</p> <p>Results</p> <p>Initially we treated the patient with prednisolone pulse therapy and additive antibiotic therapy. For maintenance therapy we administered budesonide. The patient underwent clinical, laboratory and endoscopic follow-up over a three-year period. The stricture healed and was easy to pass. A relapse in the cecum at the ileocecal valve again improved under steroid and antibiotic therapy.</p> <p>Conclusions</p> <p>We present a novel therapeutic approach for advanced stricturing FC in an adult patient which successfully avoided surgery (right hemicolectomy) over a three year follow up.</p

Evaluation of quality indicators following implementation of total mesorectal excision in primarily resected rectal cancer changed future management

Background and aims: We evaluated the outcome of primarily resected rectal cancer patients immediately after the implementation of total meserectal excision (TME) based on potential quality indicators. Patients and methods: Following initial teaching of two staff surgeons (PMS and AHH) by RJ Heald, 164 consecutive patients were analyzed. The following quality indicators were evaluated: (a) frequency of local recurrence, (b) number of resected lymph nodes, (c) selection of operative technique depending on tumor localization, (d) use of a protective loop ileostomy, and (e) frequency and type of adjuvant therapy. Results: Local recurrence rate was 8.5% after a minimum follow-up of 5years. An increasing pT category (p < 0.02) and the presence of lymph node metastases (pN+, p < 0.05) were significantly associated with local recurrence rates. The number of resected lymph nodes was significantly associated with nodal metastases rate (p < 0.02). Patients with distal third rectal cancer underwent significantly more often an abdominoperineal amputation (p < 0.0001). Clinical course, but not the rate of anastomotic leakage (9.5%) itself was influenced by using a protective loop ileostomy. Forty-two (29.7%) patients received adjuvant therapy; however, local recurrence rate was higher in patients with adjuvant chemo-/radiotherapy (14.2% vs. 6.1%). Conclusions: The local recurrence rate of 8.5% demonstrates that through consequent implementation of TME excellent onclogical results can be achieved. The number of resected lymph nodes significantly influenced the pN category. The primary construction of a protective loop ileostomy after TME became standard. Neoadjuvant chemoradiation was systematically introduced in order to improve local tumor control and prevent abdominoperineal amputations. No conclusions can be drawn concerning adjuvant therap

Analysis of microsatellite instability in colorectal carcinoma by microfluidic-based chip electrophoresis

Microsatellite analysis is an important tool in clinical research and molecular diagnostics because microsatellite instability (MSI) occurs frequently in various types of cancer. Approximately 10–15% of colorectal, gastric and endometrial carcinomas are associated with MSI, and this has an impact on clinical prognosis. The microsatellite loci Bat25, Bat26, D2S123, D5S346 and D17S250, recommended by the Bethesda guidelines, were analysed by microfluidic-based on-chip electrophoresis in 40 cases of colon carcinoma with known MSI status. In all cases, microfluidic separation of the PCR amplicons resulted in highly resolved, distinct patterns of each of the five microsatellite loci. Detection of MSI could be demonstrated by microsatellite-loci-associated, well-defined deviations in the electropherogram profiles of tumour and non-tumour material, and confirmed the classification of MSI cases performed by conventional technology. In conclusion, microfluidic chip technology is a simple and reliable approach for MSI detection that allows label-free and very fast analysis of microsatellite amplicons

COX-2 mRNA Expression is Significantly Increased in Acid-exposed Compared to Nonexposed Squamous Epithelium in Gastroesophageal Reflux Disease

Background: Little is known about the role of cyclooxygenase (COX)-2 in gastroesophageal reflux disease (GERD) and the development of Barrett's metaplasia. The objectives of this study were to further analyze COX-2 mRNA expression in patients with GERD compared to Barrett's esophagus (BE) and Barrett's cancer (BC). Methods: Tissue samples from 110 patients with GERD (n = 43), BE (n = 20), and BC (n = 47) were obtained in routine upper GI endoscopy. Expression levels of COX-2 were measured by quantitative real-time reverse trancriptase polymerase chain reaction (RT-PCR). Also, 24-h pH monitoring was performed in all patients of the GERD study group and the DeMeester composite score was used to match COX-2 mRNA expression with the severity of acid exposure in the lower esophagus. Results: COX-2 mRNA is progressively upregulated within the metaplasia-dysplasia-adenocarcinoma (MDA) sequence (p = 0.001). COX-2 levels of the squamous epithelium in the distal esophagus from patients with GERD and a pathologic mean DeMeester score (>14.72) were significantly higher than in patients with normal DeMeester scores (p = 0.01). Conclusion: In summary our findings suggest that alterations in COX-2 mRNA expression occur independently of endoscopic or histologic signs of GERD in the acid-exposed squamous epithelium of the distal esophagus. However, this early COX-2 increase in GERD is further upregulated within the MDA sequence for yet unknown reason

Control of mitogenic and motogenic pathways by miR-198, diminishing hepatoma cell growth and migration

Abstract Hepatocellular carcinoma (HCC) is one of the leading causes of cancer deaths, worldwide. MicroRNAs, inhibiting gene expression by targeting various transcripts, are involved in genomic dysregulation during hepatocellular tumorigenesis. In previous studies, microRNA-198 (miR-198) was shown to be significantly downregulated in HCV-positive hepatocellular carcinoma (HCC). Herein, the function of miR-198 in hepatocellular carcinoma cell growth and gene expression was studied. In hepatoma cell-types with low levels of liver-specific transcription factor HNF1α indicating a low differentiation grade, miR-198 expression was most downregulated. However, miR-198 treatment did not restore the expression of the liver-specific transcription factors HNF1α or HNF4α. Importantly, overexpression of miR-198 in Pop10 hepatoma cells markedly reduced cell growth. In agreement, comprehensive gene expression profiling by microarray hybridisation and real-time quantification revealed that central signal transducers of proliferation pathways were downregulated by miR-198. In contrast, genes mediating cellular adherence were highly upregulated by miR-198. Thus, the low expression of E-cadherin and claudin-1, involved in cell adhesion and cell-cell contacts, was abolished in hepatoma cells after miR-198 overexpression. This definite induction of both proteins by miR-198 was shown to be accompanied by a significantly impaired migration activity of hepatoma Pop10 cells. In conclusion, miR-198 acts as a tumor suppressor by repression of mitogenic and motogenic pathways diminishing cell growth and migration

A placebo-controlled randomised trial of budesonide for PBC following an insufficient response to UDCA

Background & Aims: In patients with primary biliary cholangitis (PBC), the efficacy of budesonide, a synthetic corticosteroid displaying high first-pass metabolism, is unresolved. In a placebo-controlled, double-blind trial, we evaluated the added-value of budesonide in those with PBC and ongoing risk of progressive disease despite ursodeoxycholic acid (UDCA) treatment. Methods: We evaluated 62 patients with PBC who had histologically confirmed hepatic inflammatory activity, according to the Ishak score, and an alkaline phosphatase (ALP) >1.5x upper limit of normal (ULN), after at least 6 months of UDCA therapy. Participants were randomly assigned 2:1 to receive budesonide (9 mg/day) or placebo once daily, for 36 months, with UDCA treatment (12-16 mg/kg body weight/day) maintained. Primary efficacy was defined as improvement of liver histology with respect to inflammation and no progression of fibrosis. Secondary outcomes included changes in biochemical markers of liver injury. Results: Recruitment challenges resulted in a study that was underpowered for the primary efficacy analysis. Comparing patients with paired biopsies only (n = 43), the primary histologic endpoint was not met (p>0.05). The proportion of patients with ALP = 15% decrease in ALP and normal bilirubin was higher in the budesonide group than in the placebo group at 12, 24, and 36 months (p Conclusion: Budesonide add-on therapy was not associated with improved liver histology in patients with PBC and insufficient response to UDCA; however, improvements in biochemical markers of disease activity were demonstrated in secondary analyses. Lay summary: Around one-third of patients with primary biliary cholangitis (PBC) needs additional medical therapy alongside ursodeoxycholic acid (UDCA) treatment. In this clinical trial, the addition of the corticosteroid budesonide did not improve liver histology; there were however relevant improvements in liver blood tests. (C) 2020 European Association for the Study of the Liver. Published by Elsevier B.V.Peer reviewe

Intratumoral heterogeneity of microRNA expression in rectal cancer

Introduction: An increasing number of studies have investigated microRNAs (miRNAs) as potential markers of diagnosis, treatment and prognosis. So far, agreement between studies has been minimal, which may in part be explained by intratumoral heterogeneity of miRNA expression. The aim of the present study was to assess the heterogeneity of a panel of selected miRNAs in rectal cancer, using two different technical approaches. Materials and Methods: The expression of the investigated miRNAs was analysed by real-time quantitative polymerase chain reaction (RT-qPCR) and in situ hybridization (ISH) in tumour specimens from 27 patients with T3-4 rectal cancer. From each tumour, tissue from three different luminal localisations was examined. Inter- and intra-patient variability was assessed by calculating intraclass correlation coefficients (ICCs). Correlations between RT-qPCR and ISH were evaluated using Spearman's correlation. Results: ICCsingle (one sample from each patient) was higher than 50% for miRNA-21 and miRNA-31. For miRNA-125b, miRNA-145, and miRNA-630, ICCsingle was lower than 50%. The ICCmean (mean of three samples from each patient) was higher than 50% for miRNA-21(RT-qPCR and ISH), miRNA-125b (RT-qPCR and ISH), miRNA-145 (ISH), miRNA-630 (RT-qPCR), and miRNA-31 (RT-qPCR). For miRNA-145 (RT-qPCR) and miRNA-630 (ISH), ICCmean was lower than 50%. Spearman correlation coefficients, comparing results obtained by RT-qPCR and ISH, respectively, ranged from 0.084 to 0.325 for the mean value from each patient, and from -0.085 to 0.515 in the section including the deepest part of the tumour. Conclusion: Intratumoral heterogeneity may influence the measurement of miRNA expression and consequently the number of samples needed for representative estimates. Our findings with two different methods suggest that one sample is sufficient for adequate assessment of miRNA-21 and miRNA-31, whereas more samples would improve the assessment of miRNA-125b, miRNA-145, and miRNA-630. Interestingly, we found a poor correlation between the expression estimates obtained by RT-qPCR and ISH, respectively