ABSTRACT
Theranostic assays are based on single-gene testing, but the ability of next-generation sequencing (NGS) to interrogate numerous genetic alterations will progressively replace single-gene assays. Although NGS was evaluated to screen for theranostic mutations, its usefulness in clinical practice on large series of samples remains to be demonstrated. NGS performance was assessed following guidelines. TaqMan probes and NGS were compared for their ability to detect EGFR and KRAS mutations, and NGS mutation profiles were analyzed on a large series of non-small-cell lung cancers (n = 1343). The R2 correlation between expected and measured allelic ratio, using commercial samples, was >0.96. Mutation detection threshold was 2% for 10 ng of DNA input. κ Scores for TaqMan versus NGS were 0.99 (95% CI, 0.97-1.00) for EGFR and 0.98 (95% CI, 0.97-1.00) for KRAS after exclusion of rare EGFR (n = 40) and KRAS (n = 60) mutations. NGS identified 693 and 292 mutations in validated and potential oncogenic drivers, respectively. Significant associations were found between EGFR and PI3KCA or CTNNB1 and between KRAS and STK11. Potential oncogenic driver mutations or gene amplifications were more frequent in validated oncogenic driver nonmutated samples. This work is a proof of concept that targeted NGS is accessible in routine screening, including large screening, at reasonable cost. Clinical data should be collected and implemented in specific databases to make molecular data meaningful for direct patients' benefit.
Subject(s)
Carcinoma, Non-Small-Cell Lung/genetics , High-Throughput Nucleotide Sequencing/methods , Lung Neoplasms/genetics , Humans , Mutation/genetics , Oncogenes , Proto-Oncogene Proteins p21(ras)/genetics , Reproducibility of ResultsSubject(s)
Cytomegalovirus Infections/complications , Hepatitis, Autoimmune/etiology , Hepatitis/etiology , Pregnancy Complications/etiology , Female , Giant Cells/pathology , Hepatitis/diagnosis , Hepatitis/immunology , Hepatitis, Autoimmune/diagnosis , Hepatitis, Autoimmune/pathology , Humans , Pregnancy , Pregnancy Complications/immunology , Pregnancy Complications, Infectious/virology , Young AdultABSTRACT
Sarcoidosis is a systemic granulomatous disease which may involve many organs. In approximately 95% of patients there is liver involvement, with noncaseating hepatic granulomas occurring in 21 to 99% of patients with sarcoidosis. Liver involvement is usually asymptomatic and limited to mild to moderate abnormalities in liver biochemistry. The occurrence of jaundice in sarcoidosis is rare; extensive imaging procedures and the examination of liver biopsies permit a precise diagnostic. Ductopenia associated with sarcoidosis has been reported in less than 20 cases and can lead to biliary cirrhosis and liver- related death. We report here on a case of ductopenia-related sarcoidosis in which primary biliary cirrhosis and extrahepatic cholestasis have been carefully excluded. The patient follow up was 8 years. Although ursodesoxycholic acid appears to improve liver biochemistry it does not preclude the rapid occurrence of extensive fibrosis. A review of the literature of reported cases of ductopenia related to sarcoidosis is provided.
ABSTRACT
Increased ferritin levels are common in the course of chronic hepatitis C, regardless of antiviral therapy. Usually, this increase in ferritin levels has minimal clinical and biological impact, and drops after therapy discontinuation. We report here on a dramatic increase in ferritin levels in a cirrhotic patient with hepatitis C treated by ribavirin monotherapy and oral iron sulphate, and discuss the possible mechanisms of this deleterious effect.
Subject(s)
Antiviral Agents/adverse effects , Ferrous Compounds/adverse effects , Hepatitis C, Chronic/drug therapy , Iron Overload/chemically induced , Ribavirin/adverse effects , Drug Therapy, Combination , Female , Ferritins/blood , Hepatitis C, Chronic/blood , Humans , Middle AgedSubject(s)
Scurvy , Administration, Oral , Aged , Antioxidants/administration & dosage , Antioxidants/therapeutic use , Ascorbic Acid/administration & dosage , Ascorbic Acid/therapeutic use , Drug Therapy, Combination , Folic Acid/administration & dosage , Folic Acid/therapeutic use , Humans , Male , Scurvy/diagnosis , Scurvy/drug therapy , Scurvy/etiology , Time Factors , Treatment OutcomeABSTRACT
Purine analogues are major drugs in the treatment of inflammatory bowel diseases (IBD). We present four cases of nodular regenerative hyperplasia of the liver (NRH) developed in patients with IBD treated with azathioprine. All patients had either abnormal liver tests and/or low platelet count. Although biochemical and hematological abnormalities regressed after azathioprine withdrawal, the long term evolution of the hepatic lesions (and the risk to develop further complications including portal hypertension) remains to be determined. Male gender seems to be a major risk factor by providing a predisposing pharmacogenetic profile of purine analogue metabolism. Clinicians should be aware of this serious complication which may occur with any of the purine analogues (azathioprine, 6-mercaptopurine, and 6-thioguanine).
Subject(s)
Azathioprine/adverse effects , Focal Nodular Hyperplasia/chemically induced , Immunosuppressive Agents/adverse effects , Inflammatory Bowel Diseases/drug therapy , Adult , Azathioprine/therapeutic use , Humans , Immunosuppressive Agents/therapeutic use , Male , Middle Aged , Risk FactorsABSTRACT
Combination therapy with steroids and azathioprine is the reference treatment for autoimmune hepatitis, but potential adverse effects are numerous and intolerance can occur. We report a patient with a well-documented type 1 autoimmune hepatitis intolerant to corticosteroids and azathioprine therapy, in whom eight years of ursodeoxycholic acid monotherapy was associated with biochemical and histological remission.
