Gastrointestinal tissue‐based molecular biomarkers: A practical categorization based on the 2019 WHO Classification of Epithelial Digestive Tumours

Molecular biomarkers have come to constitute one of the cornerstones of oncological pathology. The method of classification not only directly affects the manner in which patients are diagnosed and treated, but also guides the development of drugs and of artificial intelligence tools. The aim of this article is to organise and update gastrointestinal molecular biomarkers in order to produce an easy-to-use guide for routine diagnostics. For this purpose, we have extracted and reorganised the molecular information on epithelial neoplasms included in the 2019 World Health Organization classification of tumours. Digestive system tumours, 5th edn

Low incidence of positive smooth muscle antibody and high incidence of isolated IgM elevation in Chinese patients with autoimmune hepatitis and primary biliary cirrhosis overlap syndrome: a retrospective study

<p/> <p>Background</p> <p>Up to now, few data are available regarding the clinical characteristics of autoimmune hepatitis and primary biliary cirrhosis overlap syndrome. The study was to investigate and analyze the prevalent and clinical features of Chinese patients with this disease.</p> <p>Methods</p> <p>Clinical data on patients diagnosed as autoimmune hepatitis and primary biliary cirrhosis overlap syndrome in our hospital from January 2001 to December 2006 were collected and analyzed.</p> <p>Results</p> <p>Overlap syndrome of autoimmune hepatitis and primary biliary cirrhosis accounted for 10.33% of patients with autoimmune liver diseases during the past six years. For these patients with overlap syndrome, xanthochromia, lethargy and anorexia were the predominant complaints; a low incidence (14/146) of smooth muscle antibody positivity and a high incidence (37/89) of isolated IgM elevation were the main serological characteristics.</p> <p>Conclusions</p> <p>Overlap syndrome of autoimmune hepatitis and primary biliary cirrhosis was not rare in Chinese patients with clinical manifests of autoimmune liver diseases. Overlap of the diseases should not be disregarded when isolated IgM elevation was exhibited, and smooth muscle antibody might have little diagnostic significance in the overlap syndrome. If it was difficult to make a definite diagnosis, liver biopsy was necessary.</p

Percutaneous Cryoablation of Pulmonary Metastases from Colorectal Cancer

Objective: To evaluate the safety and efficacy of cryoablation for metastatic lung tumors from colorectal cancer. Methods: The procedures were performed on 24 patients (36–82 years of age, with a median age of 62; 17 male patients, 7 female patients) for 55 metastatic tumors in the lung, during 30 sessions. The procedural safety, local progression free interval, and overall survival were assessed by follow-up computed tomographic scanning performed every 3–4 months. Results: The major complications were pneumothorax, 19 sessions (63%), pleural effusion, 21 sessions (70%), transient and self-limiting hemoptysis, 13 sessions (43%) and tract seeding, 1 session (3%). The 1- and 3-year local progression free intervals were 90.8 % and 59%, respectively. The 3-years local progression free intervals of tumors #15 mm in diameter was 79.8 % and that of tumors.15 mm was 28.6 % (p = 0.001; log-rank test). The 1- and 3-year overall survival rates were 91% and 59.6%, respectively. Conclusion: The results indicated that percutaneous cryoablation is a feasible treatment option. The local progression fre

Protein Phosphatase-1 Activates CDK9 by Dephosphorylating Ser175

The cyclin-dependent kinase CDK9/cyclin T1 induces HIV-1 transcription by phosphorylating the carboxyterminal domain (CTD) of RNA polymerase II (RNAPII). CDK9 activity is regulated by protein phosphatase-1 (PP1) which was previously shown to dephosphorylate CDK9 Thr186. Here, we analyzed the effect of PP1 on RNAPII phosphorylation and CDK9 activity. The selective inhibition of PP1 by okadaic acid and by NIPP1 inhibited phosphorylation of RNAPII CTD in vitro and in vivo. Expression of the central domain of NIPP1 in cultured cells inhibited the enzymatic activity of CDK9 suggesting its activation by PP1. Comparison of dephosphorylation of CDK9 phosphorylated by (32P) in vivo and dephosphorylation of CDK9's Thr186 analyzed by Thr186 phospho-specific antibodies, indicated that a residue other than Thr186 might be dephosphorylated by PP1. Analysis of dephosphorylation of phosphorylated peptides derived from CDK9's T-loop suggested that PP1 dephosphorylates CDK9 Ser175. In cultured cells, CDK9 was found to be phosphorylated on Ser175 as determined by combination of Hunter 2D peptide mapping and LC-MS analysis. CDK9 S175A mutant was active and S175D – inactive, and dephosphorylation of CDK9's Ser175 upregulated HIV-1 transcription in PP1-dependent manner. Collectively, our results point to CDK9 Ser175 as novel PP1-regulatory site which dephosphorylation upregulates CDK9 activity and contribute to the activation of HIV-1 transcription

Quality assurance in pathology in colorectal cancer screening and diagnosis—European recommendations

In Europe, colorectal cancer is the most common newly diagnosed cancer and the second most common cause of cancer deaths, accounting for approximately 436,000 incident cases and 212,000 deaths in 2008. The potential of high-quality screening to improve control of the disease has been recognized by the Council of the European Union who issued a recommendation on cancer screening in 2003. Multidisciplinary, evidence-based European Guidelines for quality assurance in colorectal cancer screening and diagnosis have recently been developed by experts in a pan-European project coordinated by the International Agency for Research on Cancer. The full guideline document consists of ten chapters and an extensive evidence base. The content of the chapter dealing with pathology in colorectal cancer screening and diagnosis is presented here in order to promote international discussion and collaboration leading to improvements in colorectal cancer screening and diagnosis by making the principles and standards recommended in the new EU Guidelines known to a wider scientific community

Annex to Quirke et al. Quality assurance in pathology in colorectal cancer screening and diagnosis: annotations of colorectal lesions

Multidisciplinary, evidence-based European Guidelines for quality assurance in colorectal cancer screening and diagnosis have recently been developed by experts in a pan-European project coordinated by the International Agency for Research on Cancer. The full guideline document includes a chapter on pathology with pan-European recommendations which take into account the diversity and heterogeneity of health care systems across the EU. The present paper is based on the annex to the pathology chapter which attempts to describe in greater depth some of the issues raised in the chapter in greater depth, particularly details of special interest to pathologists. It is presented here to make the relevant discussion known to a wider scientific audience