Lymph node core biopsies reliably permit diagnosis of lymphoproliferative diseases. Real‐World Experience from 554 sequential core biopsies from a single centre

INTRODUCTION: Whilst excision biopsy is traditionally preferred, advances in radiological and histological techniques warrant a re-look at core biopsy as a viable primary diagnostic method. METHOD: Over a 3-year period, all patients who underwent core biopsy to investigate lymphoma at our centre were included. RESULTS: 554 consecutive patients were included (40.1% prior lymphoma and 59.4% new presentations). Three or more cores were taken in 420 (75.8%) cases. Median time from request to biopsy and biopsy to histology report was 2 (0-40) days and 7 (1-24) days respectively. 510/544 (93.8%) biopsies were diagnostic. There was no difference in whether the biopsy was diagnostic based on indication (new vs. relapsed lymphoma) (p=0.445), whether biopsy was PET-directed (p=0.507), for T-cell lymphoma (p=0.468) or nodal vs. extra-nodal (p=0.693). Thirty-eight patients (6.9%) required a second biopsy due to inadequate tissue. In a patient experience survey, only 13.9% reported any complications (1 self-limiting minor bleeding, 4 bruising) whilst 16.7% reported any discomfort beyond 12 hours. CONCLUSION: Core biopsy performed by experienced radiologists and analysed by expert haemato-pathologists is a reliable, well-tolerated method for diagnosing lymphoma and confirming relapse. Multiple cores can be obtained under local anaesthetic yielding sufficient material in the majority of cases

Interrogation of transcriptomic changes associated with drug-induced hepatic sinusoidal dilatation in colorectal cancer

Drug-related sinusoidal dilatation (SD) is a common form of hepatotoxicity associated with oxaliplatin-based chemotherapy used prior to resection of colorectal liver metastases (CRLM). Recently, hepatic SD has also been associated with anti-delta like 4 (DLL4) cancer therapies targeting the NOTCH pathway. To investigate the hypothesis that NOTCH signaling plays an important role in drug-induced SD, gene expression changes were examined in livers from anti-DLL4 and oxaliplatin-induced SD in non-human primate (NHP) and patients, respectively. Putative mechanistic biomarkers of bevacizumab (bev)-mediated protection against oxaliplatin-induced SD were also investigated. RNA was extracted from whole liver sections or centrilobular regions by laser-capture microdissection (LCM) obtained from NHP administered anti-DLL4 fragment antigen-binding (F(ab’)2 or patients with CRLM receiving oxaliplatin-based chemotherapy with or without bev. mRNA expression was quantified using high-throughput real-time quantitative PCR. Significance analysis was used to identify genes with differential expression patterns (false discovery rate (FDR) < 0.05). Eleven (CCL2, CCND1, EFNB2, ERG, ICAM1, IL16, LFNG, NOTCH1, NOTCH4, PRDX1, and TGFB1) and six (CDH5, EFNB2, HES1, IL16, MIK67, HES1 and VWF) candidate genes were differentially expressed in the liver of anti-DLL4- and oxaliplatin-induced SD, respectively. Addition of bev to oxaliplatin-based chemotherapy resulted in differential changes in hepatic CDH5, HEY1, IL16, JAG1, MMP9, NOTCH4 and TIMP1 expression. This work implicates NOTCH and IL16 pathways in the pathogenesis of drug-induced SD and further explains the hepato-protective effect of bev in oxaliplatin-induced SD observed in CRLM patients

Intestinal strongyloidiasis and hyperinfection syndrome

In spite of recent advances with experiments on animal models, strongyloidiasis, an infection caused by the nematode parasite Strongyloides stercoralis, has still been an elusive disease. Though endemic in some developing countries, strongyloidiasis still poses a threat to the developed world. Due to the peculiar but characteristic features of autoinfection, hyperinfection syndrome involving only pulmonary and gastrointestinal systems, and disseminated infection with involvement of other organs, strongyloidiasis needs special attention by the physician, especially one serving patients in areas endemic for strongyloidiasis. Strongyloidiasis can occur without any symptoms, or as a potentially fatal hyperinfection or disseminated infection. Th(2 )cell-mediated immunity, humoral immunity and mucosal immunity have been shown to have protective effects against this parasitic infection especially in animal models. Any factors that suppress these mechanisms (such as intercurrent immune suppression or glucocorticoid therapy) could potentially trigger hyperinfection or disseminated infection which could be fatal. Even with the recent advances in laboratory tests, strongyloidiasis is still difficult to diagnose. But once diagnosed, the disease can be treated effectively with antihelminthic drugs like Ivermectin. This review article summarizes a case of strongyloidiasis and various aspects of strongyloidiasis, with emphasis on epidemiology, life cycle of Strongyloides stercoralis, clinical manifestations of the disease, corticosteroids and strongyloidiasis, diagnostic aspects of the disease, various host defense pathways against strongyloidiasis, and available treatment options

High-resolution mapping of the 11q13 amplicon and identification of a gene, TAOS1, that is amplified and overexpressed in oral cancer cells

Amplification of chromosomal band 11q13 is a common event in human cancer. It has been reported in about 45% of head and neck carcinomas and in other cancers including esophageal, breast, liver, lung, and bladder cancer. To understand the mechanism of 11q13 amplification and to identify the potential oncogene(s) driving it, we have fine-mapped the structure of the amplicon in oral squamous cell carcinoma cell lines and localized the proximal and distal breakpoints. A 5-Mb physical map of the region has been prepared from which sequence is available. We quantified copy number of sequence-tagged site markers at 42–550 kb intervals along the length of the amplicon and defined the amplicon core and breakpoints by using TaqMan-based quantitative microsatellite analysis. The core of the amplicon maps to a 1.5-Mb region. The proximal breakpoint localizes to two intervals between sequence-tagged site markers, 550 kb and 160 kb in size, and the distal breakpoint maps to a 250 kb interval. The cyclin D1 gene maps to the amplicon core, as do two new expressed sequence tag clusters. We have analyzed one of these expressed sequence tag clusters and now report that it contains a previously uncharacterized gene, TAOS1 (tumor amplified and overexpressed sequence 1), which is both amplified and overexpressed in oral cancer cells. The data suggest that TAOS1 may be an amplification-dependent candidate oncogene with a role in the development and/or progression of human tumors, including oral squamous cell carcinomas. The approach described here should be useful for characterizing amplified genomic regions in a wide variety of tumors

PCA and hierarchical clustering of NHP FFPE LCM hepatic regions and whole liver samples with or without anti-DLL4-associated SD based on their gene expression with FDR cut off at 0.25.

<p>Results from microfluidic high-throughput RT-qPCR were normalized by calculating–ΔCt using the average of reference genes. PCA <b>(A)</b> and hierarchical clustering based on Pearson correlation <b>(B)</b> were undertaken using genes with differential expression (FDR<0.25) between the LCM hepatic regions derived from liver samples of NHPs with SD present (moderate SD severity score 2 (anti-DLL4 15 mg/kg) n = 6)) and absent (SD severity score 0 (vehicle) (n = 6)) LCM hepatic regions. PCA <b>(C)</b> and hierarchical clustering based on Pearson correlation <b>(D)</b> were undertaken using genes with differential expression (FDR<0.25) between whole liver samples of NHPs with SD present (mild to severe SD severity scores 1–3 (anti-DLL4 5–50 mg/kg) (n = 17)) and absent (SD severity score 0 (vehicle or anti-DLL4 5 mg/kg) (n = 7)). PCA data are presented as spheres in PC1, PC2 and PC3 3 dimensional (3-D) space. The axes have been rotated to highlight the separation of the distinct clusters. The blue spheres surrounded with blue line represent the samples without SD and the red spheres surrounded with red line represent the samples with SD. The silver, blue, and pink axes represent principal components 1, 2 and 3 respectively <b>(A and C)</b>. In hierarchical clustering, each row represents a gene and each column represents a sample. Red squares indicate high gene expression; green squares indicate low gene expression <b>(B and D)</b>.</p

Box-plot indicating gene affected by an overall SD effect among oxaliplatin (+/- bev) treated CRLM patients (SD severity score 0–1 (n = 48) vs. SD severity score 2–3 (n = 13)).

<p>Two-way ANOVA with treatment and SD status as factors was used. P value and FDR<0.05 are indicated in each box plot graph. OX = oxaliplatin, Bev = bevacizumab.</p

Box-plots indicating genes affected by an overall treatment effect (oxaliplatin (n = 38) vs. oxaliplatin + bev (n = 23)).

<p>Two-way ANOVA with treatment and SD status as factors was used. P-value and FDR < 0.05 are indicated in each box plot graph <b>(A-C)</b>. OX = oxaliplatin, Bev = bevacizumab.</p