16 research outputs found
Sentinel node detection in early breast cancer with intraoperative portable gamma camera: UK experience.
PURPOSE: Access to nuclear medicine department for sentinel node imaging remains an issue in number of hospitals in the UK and many parts of the world. Sentinella(®) is a portable imaging camera used intra-operatively to produce real time visual localisation of sentinel lymph nodes. METHODS: Sentinella(®) was tested in a controlled laboratory environment at our centre and we report our experience on the first use of this technology from UK. Moreover, preoperative scintigrams of the axilla were obtained in 144 patients undergoing sentinel node biopsy using conventional gamma camera. Sentinella(®) scans were done intra-operatively to correlate with the pre-operative scintigram and to determine presence of any residual hot node after the axilla was deemed to be clear based on the silence of the hand held gamma probe. RESULTS: Sentinella(®) detected significantly more nodes compared with CGC (p < 0.0001). Sentinella(®) picked up extra nodes in 5/144 cases after the axilla was found silent using hand held gamma probe. In 2/144 cases, extra nodes detected by Sentinella(®) confirmed presence of tumour cells that led to a complete axillary clearance. CONCLUSIONS: Sentinella(®) is a reliable technique for intra-operative localisation of radioactive nodes. It provides increased nodal visualisation rates compared to static scintigram imaging and proves to be an important tool for harvesting all hot sentinel nodes. This portable gamma camera can definitely replace the use of conventional lymphoscintigrams saving time and money both for patients and the health system
Aesthetic outcome after breast conserving surgery and either intraoperative radiotherapy or whole breast external beam radiotherapy for early breast cancer: Objective assessment of patients in a randomized controlled trial in Lublin, Poland
The international randomized controlled TARGIT A (TARGeted Intraoperative radiotherapy) trial demonstrated non-inferiority between the technique of TARGIT (Intra-Operative RadioTherapy (IORT) with Intrabeam®) and whole-breast external beam radiotherapy (EBRT) as part of the treatment for women with early breast cancer. The aim of this sub-study was to see if the single high dose of IORT leads to impaired aesthetic outcome in a group of patients participating in the trial at a single site. Frontal digital photographs were taken of women and analyzed, blinded to treatment received, by BCCT.core software. This produced scores for various measures of color. 29 women (16 EBRT, 13 IORT) between 49 to 79 years old had photographs taken at baseline (up to 2 days prior to surgery), and again at 12 months (median 364 days). At 12 months there was a significant difference in cEMDL (p=0.002, Wilcoxon Two-Sample test, 2-sided) and other measures, indicating more “redness” in the breasts of the women in the EBRT group compared with the IORT group. This difference persisted after adjusting for tumor size, body mass index and age (p=0.0198, multiple regression analysis). This study provides further evidence for the early beneficial effect of TARGIT on aesthetic outcome
Genetic Abolishment of Hepatocyte Proliferation Activates Hepatic Stem Cells
Quiescent hepatic stem cells (HSCs) can be activated when hepatocyte proliferation is compromised. Chemical injury rodent models have been widely used to study the localization, biomarkers, and signaling pathways in HSCs, but these models usually exhibit severe promiscuous toxicity and fail to distinguish damaged and non-damaged cells. Our goal is to establish new animal models to overcome these limitations, thereby providing new insights into HSC biology and application. We generated mutant mice with constitutive or inducible deletion of Damaged DNA Binding protein 1 (DDB1), an E3 ubiquitin ligase, in hepatocytes. We characterized the molecular mechanism underlying the compensatory activation and the properties of oval cells (OCs) by methods of mouse genetics, immuno-staining, cell transplantation and gene expression profiling. We show that deletion of DDB1 abolishes self-renewal capacity of mouse hepatocytes in vivo, leading to compensatory activation and proliferation of DDB1-expressing OCs. Partially restoring proliferation of DDB1-deficient hepatocytes by ablation of p21, a substrate of DDB1 E3 ligase, alleviates OC proliferation. Purified OCs express both hepatocyte and cholangiocyte markers, form colonies in vitro, and differentiate to hepatocytes after transplantation. Importantly, the DDB1 mutant mice exhibit very minor liver damage, compared to a chemical injury model. Microarray analysis reveals several previously unrecognized markers, including Reelin, enriched in oval cells. Here we report a genetic model in which irreversible inhibition of hepatocyte duplication results in HSC-driven liver regeneration. The DDB1 mutant mice can be broadly applied to studies of HSC differentiation, HSC niche and HSCs as origin of liver cancer
Detection of genetic abnormalities in neoplasms from Greek patients with FAP
Aims: DNA microsatellite instability is a well-known feature of
hereditary non-polyposis colon cancer; however, its incidence in
familial adenomatous polyposis, is unclear. We report the frequency of
microsatellite instability and other genetic abnormalities in a group of
Greek patients with FAP, in relation to various clinicopathological
variables.
Methods: Thirty-four tissue specimens from 10 patients with FAP were
studied. Microsatellite instability was investigated at six loci: BAT25,
BAT26, D2S123, D5S346, D17S250 and TGF-beta R11 poly(A) tract. p53 and
K-ras mutations were also examined.
Results: Microsatellite instability was detected in two FAP
adenocarcinomas from different patients. Mutation percentages observed
were: in K-ras 45% and 50% and in p53 14% and 58%, of FAP adenomas
and adenocarcinomas, respectively. No K-ras or p53 mutations were
determined in the two microsatellite instable adenocarcinomas.
Conclusion: Microsatellite instability is detectable in a small
proportion of adenocarcinomas complicating FAP. This minority of cases
may constitute a distinct subgroup among FAP neoplasms. (C) 2002,
Elsevier Science Ltd. All rights reserved
Mutational analysis of BRAF in gallbladder carcinomas in association with K-ras and p53 mutations and microsatellite instability
Background. Little is known about the genetic changes involved in the
pathogenesis of gallbladder cancer. The aim of this study was to examine
the presence of mutations in exon 15 of the B-raf gene to investigate
its role in gallbladder carcinogenesis. Materials and methods. We
examined the mutational status in exon 15 of B-raf gene in 21
gallbladder carcinoma specimens and investigated its association with
the presence of K-ras and p53 alterations, microsatellite instability
and the clinicopathological features of tumors. Results. B-raf mutations
were observed in 7 of 21 (33%) gallbladder carcinomas examined, and all
were located at the hot spot codon 599 of exon 15. K-ras and B-raf
mutations were never in the same specimens. Conclusions. B-raf gene
mutations seem to be a quite common event in gallbladder carcinomas,
implying that B-raf may play an important role in the pathogenesis of
this tumor
Analysis of PRNP gene codon 129 polymorphism in the Greek population
Creutzfeldt-Jakob disease (CJD) is a fatal transmissible
neurodegenerative prion disease with a rapid progression comprising
familial, sporadic, iatrogenic and variant forms. A polymorphism at
codon 129 of PRNP gene has been implicated in the development of variant
CJD. We examined Met/Val allele frequencies and the genotype
distribution, with respect to the polymorphic codon 129 of PRNP gene in
348 healthy individuals from the region of Athens, Greece. The following
genotype frequencies were observed in the Greek population: Met/Met
50%, Met/Val 39% and Val/Val 11%. The presence of the Methionine
allele frequencies in various European populations, according to the
published data, increases gradually from northwestern to southeastern
countries, implying the presence of a cline. The distribution of
genotypes of Met homozygotes displays random declination across the 10
compared populations. The observed higher frequency of Met homozygotes
at codon 129 does not necessarily suggest that these populations are at
increased risk of developing CJD