Πέμπτη 25 Φεβρουαρίου 2016

Combined hepatocellular carcinoma and cholangiocarcinoma (biphenotypic) tumors: clinical characteristics, imaging features of contrast-enhanced ultrasound and computed tomography

Abstract

Background

Combined hepatocellular-cholangiocarcinoma (cHCC-CC) is an uncommon primary liver malignancy and little known about the clinical and imaging characteristics of cHCC-CC. We aim to define the demographics, imaging features of cHCC-CC on contrast-enhanced ultrasound (CEUS) and contrast-enhanced computed tomography (CT) in this study.

Methods

From January 2005 to December 2014, 45 patients with pathologically proven cHCC-CC who underwent preoperative CEUS and 43 patients who had additional CT scan in our institution were included. A retrospective review of the imaging studies and clinical data in these patients was conducted.

Results

In our series, cHCC-CC accounted for 1.6 % of all primary liver malignancy. Mean age of patient with cHCC-CC was 52.8 year (range: 28–74 year) and 88.9 % (40/45) of patients were male. Thirty of forty five patients (66.7 %) had cirrhosis and 20 % (9/45) of patients had chronic hepatitis B without cirrhosis. Alpha--fetoprotein (AFP) was elevated in 62.2 % (28/45) of patients and carbohydrate antigen 19–9 (CA19-9) elevated in 22.2 % (10/45) of patients). Both AFP and CA19-9 were simultaneously elevated in 15.6 % (7/45) of patients. Enhancement pattern resembling cholangiocarcinoma (CC) was noted in 53.3 % (24/45) of patients (on CEUS and in 30.2 % (13/43) of patients at CT. Enhancement pattern resembling hepatocellular carcinoma (HCC) was observed in 42.2 % (19/45) of patients on CEUS and in 58.1 % (25/43) of patients at CT. The percentage of tumors showing CC enhancement pattern (27.9 %, 12/43) was comparable with that of tumors showing HCC enhancement pattern (44.2 %, 19/43) on both CEUS and CT (p = 0.116).

Simultaneous elevation of tumor markers (AFP and CA19-9) or tumor marker elevation (AFP or CA19-9) in discordance with enhancement pattern on CEUS was demonstrated in 51.1 % (23/45) of patients and on CT in 53.5 % (23/43) of patients, which was significantly more than simultaneous elevation of tumor markers (AFP and CA19-9) alone (p = 0.000).

Conclusions

The clinical characteristics of cHCC-CC are similar to those of HCC. The cHCC-CC tumors display enhancement patterns resembling CC or HCC in comparable proportion on both CEUS and CT. Combination of simultaneous elevation of tumor makers (AFP and CA19-9) and tumor mark elevation (AFP or CA19-9) in discordance with presumptive imaging findings on CEUS or CT may lead significantly more patients to be suspicious of the diagnosis of cHCC-CC.



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Change in weight and waist circumference and risk of colorectal cancer: results from the Melbourne Collaborative Cohort Study

Abstract

Background

Studies reporting the association between change in weight or body mass index during midlife and risk of colorectal cancer have found inconsistent results, and only one study to date has reported the association between change in waist circumference (a measure of central adiposity) and risk of colorectal cancer.

Methods

We investigated the association between risk of colorectal cancer and changes in directly measured waist circumference and weight from baseline (1990-1994) to wave 2 (2003-2007). Cox regression, with age as the time metric and follow-up starting at wave 2, adjusted for covariates selected from a causal model, was used to estimate the Hazard Ratios (HRs) and 95 % Confidence Intervals (CIs) for the change in waist circumference and weight in relation to risk of colorectal cancer.

Results

A total of 373 cases of colorectal cancer were diagnosed during an average 9 years of follow-up of 20,605 participants. Increases in waist circumference and weight were not associated with the risk of colorectal cancer (HR per 5 cm increase in waist circumference = 1.02; 95 % CI: 0.95, 1.10; HR per 5 kg increase in weight = 0.93; 0.85, 1.02). For individuals with a waist circumference at baseline that was less than the sex-specific mean value there was a slight increased risk of colorectal cancer associated with a 5 cm increase in waist circumference at wave 2 (HR = 1.08; 0.97, 1.21).

Conclusion

Increases in waist circumference and weight during midlife do not appear to be associated with the risk of colorectal cancer.



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Erratum to: Human papillomavirus types in non-cervical high-grade intraepithelial neoplasias and invasive carcinomas from San Luis Potosí, Mexico: a retrospective cross-sectional study



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Activity-based cost analysis of hepatic tumor ablation using CT-guided high-dose rate brachytherapy or CT-guided radiofrequency ablation in hepatocellular carcinoma

To analyse and compare the costs of hepatic tumor ablation with computed tomography (CT)-guided high-dose rate brachytherapy (CT-HDRBT) and CT-guided radiofrequency ablation (CT-RFA) as two alternative minimal...

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Case 6-2016: A 10-Year-Old Boy with Abdominal Cramping and Fevers

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Presentation of Case. Dr. Hasan Merali (Pediatrics): A 10-year-old boy was seen in the gastroenterology clinic of this hospital because of intermittent abdominal cramping and fevers. The patient had been well until approximately 3 weeks before this presentation, when intermittent fevers to a…

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Genotyping of Colorectal Cancer for Cancer Precision Medicine: Results from the IPH Center for Molecular Pathology

ABSTRACT

Cancer precision medicine has opened up new avenues for the treatment of colorectal cancer (CRC). To fully realize its potential, high-throughput sequencing platforms that allow genotyping beyond KRAS need to be implemented and require performance assessment. We comprehensively analyzed first-year data of 202 consecutive formalin-fixed paraffin embedded (FFPE) CRC samples for which prospective genotyping at our institution was requested. Deep targeted genotyping was done using a semiconductor-based sequencing platform and a self-designed panel of 30 CRC-related genes. Additionally, microsatellite status (MS) was determined. Ninety-seven percent of tumor samples were suitable for sequencing and in 88% MS could be assessed. The minimal drop-out rates of 6 and 25 cases respectively were due to too low amounts or heavy degradation of DNA. Of 557 non-synonymous mutations, 90 (16%) have not been described in COSMIC at the time of data query. Forty-three cases (22%) had double- or triple mutations affecting a single gene. Sixty-four percent had genetic alterations influencing oncological therapy. Eight percent of patients (MSI phenotype: 6%; mutated POLE: 2%) were potentially eligible for treatment with immune checkpoint inhibitors. Of 56% of KRASwt CRC that potentially qualified for anti-EGFR treatment, 30% presented with mutations in BRAF/NRAS. Mutated PIK3CA was detected in 21%. In conclusion, we here present real-life routine diagnostics data that not only demonstrate the robustness and feasibility of deep targeted sequencing and MS-analysis of FFPE CRC samples but also contribute to the understanding of CRC genetics. Most importantly, in more than half of the patients our approach enabled the selection of the best treatment currently available. This article is protected by copyright. All rights reserved.



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Establishment of proliferative tetraploid cells from telomerase-immortalized normal human fibroblasts

Abstract

Aneuploidy is observed in the majority of human cancers and is considered to be causally related to carcinogenesis. Although malignant aneuploid cells are suggested to develop from polyploid cells formed in precancerous lesions, the mechanisms of this process remain elusive. This is partly because no experimental model is available where nontransformed polyploid human cells propagate in vitro. We previously showed that proliferative tetraploid cells can be established from normal human fibroblasts by treatment with the spindle poison demecolcine (DC). However, the limited lifespan of these cells hampered detailed analysis of a link between chromosomal instability and the oncogenic transformation of polyploid cells. Here, we report the establishment of proliferative tetraploid cells from the telomerase-immortalized normal human fibroblast cell line TIG-1. Treatment of immortalized diploid cells with DC for 4 days resulted in proliferation of cells with tetraploid DNA content and near-tetraploid/tetraploid chromosome counts. Established tetraploid cells had functional TP53 despite growing at almost the same rate as diploid cells. The frequency of clonal and sporadic chromosome aberrations in tetraploid cells was higher than in diploid cells and in one experiment, gradually increased with repeated subculture. This study suggests that tetraploid cells established from telomerase-immortalized normal human fibroblasts can be a valuable model for studying chromosomal instability and the oncogenic potential of polyploid cells. This article is protected by copyright. All rights reserved.



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