Clinical characteristics and survival outcomes of patients with primary central nervous system lymphoma treated with high-dose methotrexate-based polychemotherapy and consolidation therapies.

Given the rarity of primary central nervous system lymphoma (PCNSL), evaluations of different high-dose methotrexate-(HD-MTX)-based treatment regimens is sparse. This retrospective, multicenter study evaluates clinical characteristics and outcomes (progression-free, overall and disease-specific survival) after five HD-MTX-based polychemotherapeutic regimens and two consolidation therapies. 346 patients with histologically confirmed PCNSL, treated with ≥ 1 cycle HD-MTX-based strategies (≥3g/m/cycle) were included.

Efficacy of EUS-guided keyhole biopsies in diagnosing subepithelial lesions of the upper gastrointestinal tract.

Tissue acquisition is required for diagnosis of subepithelial lesions (SELs). However, obtaining adequate tissue remains challenging. This study investigated an EUS-guided technique using a forceps to create a channel and take multiple biopsies from the center of the lesion, therefore called endoscopic ultrasound-guided keyhole biopsy (EUS-KB).

Real-world routine diagnostic molecular analysis for TP53 mutational status is recommended over p53 immunohistochemistry in B-cell lymphomas.

Previous studies in patients with mature B-cell lymphomas (MBCL) have shown that pathogenic TP53 aberrations are associated with inferior chemotherapeutic efficacy and survival outcomes. In solid malignancies, p53 immunohistochemistry is commonly used as a surrogate marker to assess TP53 mutations, but this correlation is not yet well-established in lymphomas. This study evaluated the accuracy of p53 immunohistochemistry as a surrogate marker for TP53 mutational analysis in a large real-world patient cohort of 354 MBCL patients within routine diagnostic practice.

Targeted next-generation sequencing has incremental value in the diagnostic work-up of patients with suspect pancreatic masses; a multi-center prospective cross sectional study.

Background: The diagnostic process of patients with suspect pancreatic lesions is often lengthy and prone to repeated diagnostic procedures due to inconclusive results. Targeted Next-Generation Sequencing (NGS) performed on cytological material obtained with fine needle aspiration (FNA) or biliary duct brushing can speed up this process. Here, we study the incremental value of NGS for establishing the correct diagnosis, and subsequent treatment plan in patients with inconclusive diagnosis after regular diagnostic work-up for suspect pancreatic lesions.

Safety and economic analysis of selective histopathology following cholecystectomy: multicentre, prospective, cross-sectional FANCY study.

Background: There is ongoing debate concerning the necessity of routine histopathological examination following cholecystectomy. In order to reduce the pathology workload and save costs, a selective approach has been suggested, but evidence regarding its oncological safety is lacking.

Methods: In this multicentre, prospective, cross-sectional study, all gallbladders removed for gallstone disease or cholecystitis were systematically examined by the surgeon for macroscopic abnormalities indicative of malignancy.

Oncological Safety and Potential Cost Savings of Routine vs Selective Histopathological Examination After Appendectomy: Results of the Multicenter, Prospective, Cross-Sectional FANCY Study.

Objective: To investigate the oncological safety and potential cost savings of selective histopathological examination after appendectomy.

Background: The necessity of routine histopathological examination after appendectomy has been questioned, but prospective studies investigating the safety of a selective policy are lacking.

Methods: In this multicenter, prospective, cross-sectional study, inspection and palpation of the (meso)appendix was performed by the surgeon in patients with suspected appendicitis.

Tumour-stroma ratio outperforms tumour budding as biomarker in colon cancer: a cohort study.

The tumour-stroma ratio (TSR) and tumour budding (TB) are two high-risk factors with potential to be implemented in the next TNM classification. The aim of the current study was to evaluate the practical application of the two biomarkers based on reproducibility, independency and prognostic value. Patients diagnosed with stage II or III colon cancer who underwent surgery between 2005 and 2016 were included.

Frequent mutated B2M, EZH2, IRF8, and TNFRSF14 in primary bone diffuse large B-cell lymphoma reflect a GCB phenotype.

Primary bone diffuse large B-cell lymphoma (PB-DLBCL) is a rare extranodal lymphoma subtype. This retrospective study elucidates the currently unknown genetic background of a large clinically well-annotated cohort of DLBCL with osseous localizations (O-DLBCL), including PB-DLBCL. A total of 103 patients with O-DLBCL were included and compared with 63 (extra)nodal non-osseous (NO)-DLBCLs with germinal center B-cell phenotype (NO-DLBCL-GCB).

Safety and cost analysis of selective histopathological examination following appendicectomy and cholecystectomy (FANCY study): protocol and statistical analysis plan of a prospective observational multicentre study.

Introduction: Routine histopathological examination following appendicectomy and cholecystectomy has significant financial implications and comprises a substantial portion of the pathologists' workload, while the incidence of unexpected pathology is low. The aim of the selective histopathological examination Following AppeNdicectomy and CholecystectomY (FANCY) study is to investigate the oncological safety and potential cost savings of selective histopathological examination based on macroscopic assessment performed by the surgeon.

Methods And Analysis: This is a Dutch multicentre prospective observational study, in which removed appendices and gallbladders will be systematically assessed by the operating surgeon for macroscopic abnormalities suspicious for malignant neoplasms.

Acute Clinical Manifestation of Mesenteric Heterotopic Pancreatitis: A Pre- and Postoperative Confirmed Case.

Heterotopic pancreas is a relatively uncommon congenital anomaly, defined as pancreatic tissue in ectopic sites without an anatomic and vascular continuity with the main body of the pancreas. We report the case of a 58-year-old woman who was admitted to the hospital with the clinical suspicion of a mild, acute pancreatitis. Computed tomography, magnetic resonance imaging, transabdominal ultrasound, and endoscopic ultrasound revealed a normal orthotopic pancreas and the suspicion of a large heterotopic pancreas in the small bowel mesentery with signs of acute inflammation.

Noncirrhotic Portal Hypertension in Perinatally HIV-infected Adolescents Treated With Didanosine-containing Antiretroviral Regimens in Childhood.

Background: Noncirrhotic portal hypertension (NCPH) has been reported in HIV-infected adults. Antiretroviral drugs, as well as genetic and thrombophilic predisposition, have been suggested as possible etiologic factors.

Methods: Clinical data were collected from 6 HIV-infected patients attending the Infectious Diseases Departments at respectively Emma Children's Hospital Academic Medical Centre in Amsterdam, The Thai Red Cross AIDS Research Centre, Bangkok, Imperial College Healthcare NHS Trust, London who were diagnosed with NCPH.

An intrahepatic transcriptional signature of enhanced immune activity predicts response to peginterferon in chronic hepatitis B.

Background & Aims: Differences in intrahepatic gene expression patterns may be associated with therapy response in peginterferon-treated chronic hepatitis B (CHB) patients.

Methods: We employed gene expression profiling in baseline liver biopsies of 40 CHB patients (19 HBeAg-positive; 21 HBeAg-negative) treated with peginterferon and adefovir for 48 weeks, and compared expression patterns of combined responders (HBeAg loss, HBV-DNA <2000 IU/ml, alanine aminotransferase normalization after 1 year of treatment-free follow-up) with non-responders. Genes identified by transcriptome analysis in 15 biopsies were confirmed in 25 additional biopsies by RT-qPCR.

A 3D in vitro model of differentiated HepG2 cell spheroids with improved liver-like properties for repeated dose high-throughput toxicity studies.

Immortalized hepatocyte cell lines show only a weak resemblance to primary hepatocytes in terms of gene expression and function, limiting their value in predicting drug-induced liver injury (DILI). Furthermore, primary hepatocytes cultured on two-dimensional tissue culture plastic surfaces rapidly dedifferentiate losing their hepatocyte functions and metabolic competence. We have developed a three-dimensional in vitro model using extracellular matrix-based hydrogel for long-term culture of the human hepatoma cell line HepG2.

Comparison of interobserver agreement of magnetic resonance elastography with histopathological staging of liver fibrosis.

Purpose: MR elastography (MRE) can serve as an accurate surrogate marker of liver fibrosis. For any diagnostic test that is to replace the current reference standard, interobserver agreement should be at least as good and preferably better. The objective of this study was to perform a head-to-head comparison of the interobserver agreements of MRE and liver fibrosis staging on biopsy in a single cohort of hepatitis patients.

Non-invasive evaluation of liver fibrosis: a comparison of ultrasound-based transient elastography and MR elastography in patients with viral hepatitis B and C.

Objective: To compare the diagnostic accuracy of TE and MRE and establish cutoff levels and diagnostic strategies for both techniques, enabling selection of patients for liver biopsy.

Methods: One hundred three patients with chronic hepatitis B or C and liver biopsy were prospectively included. Areas under curves (AUROC) were compared for TE and MRE for METAVIR fibrosis grade ≥ F2 and ≥F3.

Baseline hepatitis B surface antigen (HBsAg) as predictor of sustained HBsAg loss in chronic hepatitis B patients treated with pegylated interferon-α2a and adefovir.

Background: In this study, we aimed to identify baseline predictors of response in chronic hepatitis B patients treated with a combination of pegylated interferon (PEG-IFN)-α2a and adefovir.

Methods: We treated 92 chronic hepatitis B patients (44 hepatitis B e antigen [HBeAg]-positive and 48 HBeAg-negative) with HBV DNA > 100,000 copies/ml (> 17,182 IU/ml) with PEG-IFN and adefovir for 48 weeks and followed them up for 2 years. Baseline markers for HBeAg loss, combined response (HBeAg negativity, HBV DNA levels ≤ 2,000 IU/ml and alanine aminotransferase [ALT] normalization) and hepatitis B surface antigen (HBsAg) loss were evaluated.

Diagnostic accuracy of MRI in differentiating hepatocellular adenoma from focal nodular hyperplasia: prospective study of the additional value of gadoxetate disodium.

Objective: The purpose of this article is to prospectively determine the sensitivity of hepatobiliary phase gadoxetate disodium-enhanced MRI combined with standard MRI in differentiating focal nodular hyperplasia (FNH) from hepatocellular adenoma (HCA).

Subjects And Methods: Patients suspected of having FNH or HCA larger than 2 cm underwent gadoxetate disodium-enhanced MRI. Standard MRI was evaluated separately from the additional hepatobiliary phase by two blinded radiologists.

Intrahepatic response markers in chronic hepatitis B patients treated with peginterferon alpha-2a and adefovir.

Background And Aim: We investigated whether intrahepatic markers could predict response in chronic hepatitis B virus (HBV) patients treated with peg-interferon and adefovir for 48 weeks.

Methods: Intrahepatic covalently closed circular DNA (cccDNA), total intrahepatic HBV DNA and the proportion of hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) positive hepatocytes in 16 hepatitis B e antigen (HBeAg) positive and 24 HBeAg negative patients were measured at baseline and at end of treatment.

Results: Baseline intrahepatic markers were not associated with sustained virological response (SVR) defined as HBV DNA < 2000 IU/mL and persistent normal alanine aminotransferase levels at the end of follow-up (week 72).

ABCB4 deficiency: A family saga of early onset cholelithiasis, sclerosing cholangitis and cirrhosis and a novel mutation in the ABCB4 gene.

Gallstones are very common. However, there is a small group of patients with low phospholipid-associated cholelithiasis (LPAC) that is characterized by symptomatic cholelithiasis at a young age (<40 years), recurrence of biliary symptoms despite cholecystectomy and concrements or sludge in the intra- and extrahepatic biliary system. The LPAC syndrome is associated with mutations of the adenosine triphosphate-binding cassette, subfamily B, member 4 (ABCB4) gene encoding the hepatobiliary phospholipid translocator multidrug resistance protein 3 (MDR3).

Focal nodular hyperplasia and hepatic adenoma: epidemiology and pathology.

Focal nodular hyperplasia (FNH) and hepatic adenoma (HA) represent the most frequent non-vascular benign liver tumors. They are often asymptomatic. The widespread use of high-resolution imaging modalities leads to an increase of incidental detection of FNH and HA.

Detection of hepatitis B virus covalently closed circular DNA in paraffin-embedded and cryo-preserved liver biopsies of chronic hepatitis B patients.

Background: Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) may become an important predictor for treatment outcome or long-term follow-up.

Aim: To detect cccDNA in formalin-fixed, paraffin embedded (FFPE) and to compare with cryo-preserved liver tissue.

Methods: Biopsies of 56 chronic hepatitis B patients were collected.