The microRNA-15a-PAI-2 axis in cholangiocarcinoma-associated fibroblasts promotes migration of cancer cells

Background: Cholangiocarcinoma (CCA) has an abundance of tumor stroma which plays an important role in cancer progression via tumor-promoting signals. This study aims to explore the microRNA (miRNA) profile of CCA-associated fibroblasts (CCFs) and the roles of any identified miRNAs in CCA progression. Methods: miRNA expression profiles of CCFs and normal skin fibroblasts were compared by microarray. Identified downregulated miRNAs and their target genes were confirmed by real-time PCR. Their binding was confirmed by a luciferase reporter assay. The effects of conditioned-media (CM) of miRNA mimic- and antagonist-transfected CCFs were tested in CCA migration in wound healing assays. Finally, the levels of miRNA and their target genes were examined by real-time PCR and immunohistochemistry in clinical CCA samples. Results: miR-15a was identified as a downregulated miRNA in CCFs. Moreover, PAI-2 was identified as a novel target gene of miR-15a. Recombinant PAI-2 promoted migration of CCA cells. Moreover, CM from miR-15a mimic-transfected CCFs suppressed migration of CCA cells. Lower expression of miR-15a and higher expression of PAI-2 were observed in human CCA samples compared with normal liver tissues. Importantly, PAI-2 expression correlated with poor prognosis in CCA patients. Conclusions: These findings highlight the miR-15a/PAI-2 axis as a potential therapeutic target in CCA patients

Does Extending the Waiting Time of Low-Rectal Cancer Surgery after Neoadjuvant Chemoradiation Increase the Perioperative Complications?

Background. Traditionally, rectal cancer surgery is recommended 6 to 8 weeks after completing neoadjuvant chemoradiation. Extending the waiting time may increase the tumor response rate. However, the perioperative complication rate may increase. The purpose of this study was to determine the association between extending the waiting time of surgery after neoadjuvant chemoradiation and perioperative outcomes. Methods. Sixty patients with locally advanced rectal cancer who underwent neoadjuvant chemoradiation followed by radical resection at Siriraj hospital between June 2012 and January 2015 were retrospectively analyzed. Demographic data and perioperative outcomes were compared between the two groups. Results. The two groups were comparable in term of demographic parameters. The mean time interval from neoadjuvant chemoradiation to surgery was 6.4 weeks in Group A and 11.7 weeks in Group B. The perioperative outcomes were not significantly different between Groups A and B. Pathologic examination showed a significantly higher rate of circumferential margin positivity in Group A than in Group B (30% versus 9.3%, resp.; P=0.04). Conclusions. Extending the waiting to >8 weeks from neoadjuvant chemoradiation to surgery did not increase perioperative complications, whereas the rate of circumferential margin positivity decreased

Preparation and in vitro Evaluation of Ethylcellulose Coated Egg Albumin Microspheres of Diltiazem Hydrochloride

The aim of the present investigation was to develop sustained release ethylcellulose-coated egg albumin microspheres of diltiazem hydrochloride (DH) to improve patient compliance. The microspheres were prepared by the w/o emulsion thermal cross-linking method using different proportion of the polymer to drug ratio (1.0:1.0, 1.0:1.5 and 1.0:2.0). A 32 full factorial design was employed to optimize two independent variables, polymer to drug ratio (X1) and surfactant concentration (X2) on dependent variables, namely % drug loading, % drug release in 60 min (Y60) and the time required for 80 % drug release (t80) were selected as dependable variable. Optimized formulation was compared to its sustained release tablet available in market. The polymer to drug ratio was optimized to 1:1 at which a high drug entrapment efficiency 79.20% ± 0.7% and the geometric mean diameter 47.30 ± 1.5 mm were found. All batches showed a biphasic release pattern; initial burst release effect (55% DH in 1 h) and then were released completely within 6 h. In situ coating of optimized egg albumin DH microspheres using 7.5% ethylcellulose significantly reduced the burst effect and provided a slow release of DH for 8-10 h. Finally, it was concluded that ethylcellulose-coated egg albumin DH microspheres is suitable for oral SR devices in the treatment of angina pectoris, cardiac arrhythmias, and hypertension due to their size and release profile

2016 Comprehensive Update of the Banff Working Group on Liver Allograft Pathology: Introduction of Antibody-Mediated Rejection

The Banff Working Group on Liver Allograft Pathology reviewed and discussed literature evidence regarding antibody-mediated liver allograft rejection at the 11th (Paris, France, June 5-10, 2011), 12th (Comandatuba, Brazil, August 19-23, 2013), and 13th (Vancouver, British Columbia, Canada, October 5-10, 2015) meetings of the Banff Conference on Allograft Pathology. Discussion continued online. The primary goal was to introduce guidelines and consensus criteria for the diagnosis of liver allograft antibody-mediated rejection and provide a comprehensive update of all Banff Schema recommendations. Included are new recommendations for complement component 4d tissue staining and interpretation, staging liver allograft fibrosis, and findings related to immunosuppression minimization. In an effort to create a single reference document, previous unchanged criteria are also included

Benign Recurrent Intrahepatic Cholestasis: A Case Report

Benign recurrent intrahepatic cholestasis (BRIC) is an autosomal recessive cholestatic liver disease. Recurrent self-limited episodes of jaundice and severe pruritus are leading clinical manifestations. We report a 16-year-old Thai boy with three recurrent episodes of cholestasis. The first episode occurred at 30 months old. The subsequent recurrent episodes were at 13 and 16 years, respectively. Investigations including viral study, autoimmune hepatitis markers, abdominal ultrasound and magnetic resonance cholangiopancreatography (MRCP) were negative. Diagnosis of BRIC was made based on specific criteria. He was treated with cholestyramine and ursodeoxycholic acid when the first and second episodes occurred which resulted in good recovery. However, for the last recurrent episode, treatment with ursodeoxycholic acid failed to improve his condition, so his treatment was changed to rifampicin, which resulted in dramatic response. Although BRIC is a rare disease, it should be taken into account in all cases with recurrent cholestasis with normal or minimally elevated GGT level. Currently, genetic study for the mutation of ATP8B1 and ABCB11 genes are crucial for making a definite diagnosis

Diffusion-weighted magnetic resonance imaging for the assessment of liver fibrosis in chronic viral hepatitis.

BackgroundAccurate noninvasive methods for the assessment of liver fibrosis are urgently needed. This prospective study evaluated the diagnostic accuracy of diffusion-weighted magnetic resonance imaging (DWI) for the staging of liver fibrosis and proposed a diagnostic algorithm using DWI to identify cirrhosis in patients with chronic viral hepatitis.MethodsOne hundred twenty-one treatment-naïve patients with chronic hepatitis B or C were evaluated with DWI followed by liver biopsy on the same day. Breath-hold single-shot echo-planar DWI was performed to measure the apparent diffusion coefficient (ADC) of the liver and spleen. Normalized liver ADC was calculated as the ratio of liver ADC to spleen ADC.ResultsThere was an inverse correlation between fibrosis stage and normalized liver ADC (p3.25 yielded an 80% PPV for cirrhosis, and a 100% NPV to exclude cirrhosis in patients with Fibrosis-4 between 1.45 and 3.25. Only 15.7% of patients would require a liver biopsy. This sequential strategy can reduce DWI examinations by 53.7%.ConclusionNormalized liver ADC measurement on DWI is an accurate and noninvasive tool for the diagnosis of cirrhosis in patients with chronic viral hepatitis

Clinical characteristics and diagnosis of intestinal tuberculosis in clinical practice at Thailand’s largest national tertiary referral center: An 11-year retrospective review

Background Diagnosing intestinal tuberculosis (ITB) is challenging due to the low diagnostic sensitivity of current methods. This study aimed to assess the clinical characteristics and diagnosis of ITB at our tertiary referral center, and to explore improved methods of ITB diagnosis. Methods This retrospective study included 177 patients diagnosed with ITB at Siriraj Hospital (Bangkok, Thailand) during 2009–2020. Results The mean age was 49 years, 55.4% were male, and 42.9% were immunocompromised. Most diagnoses (108/177) were made via colonoscopy; 12 patients required more than one colonoscopy. Among those, the sensitivity of tissue acid-fast bacilli (AFB), presence of caseous necrosis, polymerase chain reaction (PCR), and culture was 40.7%, 13.9%, 25.7%, and 53.4%, respectively. Among patients with negative tissue histopathology, 4 (3.7%) and 13 (12.0%) were ITB positive on tissue PCR and culture, respectively. The overall sensitivity when all diagnostic methods were used was 63%. Seventy-six patients had stool tests for mycobacteria. The overall sensitivity of stool tests was 75.0%. However, when analyzing the 31 patients who underwent both endoscopy and stool testing, the sensitivity of stool testing when using tissue biopsy as a reference was 45.8%. Combining stool testing and tissue biopsy did not significantly increase the sensitivity compared to tissue biopsy alone (83.9% vs. 77.4%, respectively). Conclusion Despite the availability of PCR and culture for TB, the overall diagnostic sensitivity was found to be low. The sensitivity increased when the tests were used in combination. Repeated colonoscopy may be beneficial. Adding stool mycobacteria tests did not significantly increase the diagnostic yield if endoscopy was performed, but it could be beneficial if endoscopy is unfeasible