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Journal of clinical pathology [journal]
- Cytotoxicity of gemcitabine enhanced by polyphenolics from Aronia melanocarpa in pancreatic cancer cell line AsPC-1. [JOURNAL ARTICLE]
- J Clin Pathol 2014 Sep 17.
Extending work with brain tumours, the hypothesis that micronutrients may usefully augment anticancer regimens, chokeberry (Aronia melanocarpa) extract was tested to establish whether it has pro-apoptotic effects in AsPC-1, an established human pancreatic cell line, and whether it potentiates cytotoxicity in combination with gemcitabine. Pancreatic cancer was chosen as a target, as its prognosis remains dismal despite advances in therapy.An MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assay was used to assess the growth of the single pancreatic cancer cell line AsPC-1, alone and in comparison or combination with gemcitabine. This was backed up by flow cytometric DRAQ7 cell viability analysis. TUNEL assays were also carried out to investigate pro-apoptotic properties as responsible for the effects of chokeberry extract.Chokeberry extract alone and its IC75 value (1 µg/mL) in combination with gemcitabine were used to assess the growth of the AsPC-1 cell line. Gemcitabine in combination with chokeberry extract was more effective than gemcitabine alone. TUNEL assays showed apoptosis to be a mechanism occurring at 1 µg/mL concentration of chokeberry, with apoptotic bodies detected by both colourimetric and fluorometric methods.The implication of this study, using single cancer cell line, is that chemotherapy (at least with gemcitabine) might be usefully augmented with the use of micronutrients such as chokeberry extract.
- Assessment of suitability of the one step nucleic acid amplification (OSNA) assay as an intraoperative procedure for detection of metastasis in sentinel lymph nodes of breast cancer. [JOURNAL ARTICLE]
- J Clin Pathol 2014 Sep 12.
We aimed to assess the one step nucleic acid amplification (OSNA) assay as an intraoperative method in comparison with frozen sections (FS) for detection of metastasis in sentinel lymph nodes (SLNs) of breast cancer.100 SLNs from patients with breast carcinoma were enrolled within a 3-month period. Alternate 2 mm node slices were subjected to routine FS, and later to permanent histology, and the rest for automated molecular detection of CK19 mRNA using OSNA. FS and OSNA findings were compared with permanent histology results. Difference in turnaround time was also noted.With permanent histology as gold standard, OSNA was discrepant in 8 of 98 (3 false negative, 5 false positive) included SLNs whereas FS had 2 false negative cases. FS had higher sensitivity (89%, p=<0.001), specificity (100%, p=0.001) and concordance rate (98%) than OSNA (83%, 94% and 92%, respectively). FS showed almost perfect agreement (κ=0.929) whereas OSNA showed substantial agreement (κ=0.740) when compared with permanent histology. OSNA turnaround time was twice longer (mean of 47.7 min) than FS.Automation of SLN assessment using OSNA is a potentially useful intraoperative diagnostic tool with acceptable accuracy. Discordant findings in this study may be due to sampling allocation. Since OSNA is more time-consuming, its practical advantage over routine FS requires further study in view of current technical workflow considerations.
- Comparison of genomic abnormality in malignant mesothelioma by the site of origin. [JOURNAL ARTICLE]
- J Clin Pathol 2014 Sep 12.
Malignant mesothelioma (MM) results from the accumulation of a number of acquired genetic events at the onset. In MM, the most frequent changes are losses in 9p21, 1p36, 22q12 and 14q32, and gains in 5p, 7p and 8q24 by comparative genomic hybridisation analysis. We have examined various genomic losses and gains in MM and benign mesothelial proliferation by fluorescence in situ hybridisation (FISH) analysis. 9p21 deletion was reported to be less frequent in peritoneal than in pleural MMs. This study analysed various genomic losses and gains in MM by the site of origin using FISH analysis.We performed FISH analysis using paraffin-embedded tissues from 54 cases (40 pleural and 14 peritoneal) of MMs and compared the frequency of genomic abnormality by the site of origin.9p21 deletion was shown in 34 of 40 cases (85%) of pleural MMs, and was less frequent in five of 14 cases (36%) of peritoneal MMs (p<0.001) by FISH analysis. By contrast, 5p15 and 7p12 amplification was more significantly frequent in peritoneal than in pleural MMs. No difference between the two sites of MM in other genes was found.9p21 homozygous deletion assessed by FISH has been reported to be useful for differentiating MM from reactive mesothelial proliferation, but it should be noted that 9p21 deletion was less frequent in peritoneal MM. Our study suggests that the pathway of the genetic abnormality might vary between pleural and peritoneal MM.
- Diagnostic issues with significant tumour displacement in breast biopsies. [LETTER]
- J Clin Pathol 2014 Sep 11.
- MET T992I mutation in a case of ependymoblastoma/embryonal tumour with multilayered rosettes. [LETTER]
- J Clin Pathol 2014 Sep 5.
- Lamivudine/telbivudine-associated neuromyopathy: neurogenic damage, mitochondrial dysfunction and mitochondrial DNA depletion. [JOURNAL ARTICLE]
- J Clin Pathol 2014 Sep 4.
Myopathy or neuropathy has been associated with lamivudine/telbivudine therapy in hepatitis B patients. We aim to describe the pathological changes of lamivudine/telbivudine-associated neuromyopathy.We retrospectively recruited six patients who were diagnosed with nucleotide analogues-associated myopathy or neuropathy. Muscle and nerve biopsy were performed, and the specimens were prepared for the light microscopy and electron microscopy. Genomic DNA was extracted from frozen muscle specimens, and the mitochondrial DNA (mtDNA) content was quantified by real-time PCR.Recovery of the myopathy can be achieved after the discontinuation or changing the drugs to entecavir. Muscle and nerve biopsy revealed similar changes under either the light or electronic microscopy in all the subjects. Quantitative real-time PCR revealed decrease of mtDNA content in the affected muscle.MtDNA depletion results in mitochondrial dysfunction in the lamivudine/telbivudine-associated neuromyopathy. Myopathy was characterised by mitochondrial dysfunction accompanied with neurogenic damage due to axonal neuropathy. Ultrastructure changes of mitochondria included vacuolisation, simplification of the cristae and homogenised matrix.
- Grading of breast cancer on needle core biopsy: does a reduction in mitotic count threshold improve agreement with grade on excised specimens? [JOURNAL ARTICLE]
- J Clin Pathol 2014 Sep 2.
Accurate assessment of invasive breast cancer grade on needle core biopsy (NCB) is important as it guides treatment.To assess the agreement between grade of invasive cancer on NCB and excision and determine whether altering the mitotic count score threshold on NCB improves it.Pathology slides from patients with an NCB diagnosis of invasive breast cancer who underwent subsequent breast conservation surgery in 2012 were reviewed. Mitotic counts were assessed and tumour grade agreement between NCB and excision evaluated. The mitotic count thresholds were altered and grade agreement was reassessed.In 283/359 (79%) cases, there was concurrence on histological grade between NCB and excision. Reduction in mitotic count thresholds did not improve either overall tumour grade agreement or agreement within any subgroup of patients.In our experience, the current mitotic count score thresholds are appropriate and should be maintained.
- A real-time prospective evaluation of clinical pharmaco-economic impact of diagnostic label of 'penicillin allergy' in a UK teaching hospital. [JOURNAL ARTICLE]
- J Clin Pathol 2014 Sep 2.
To perform a pharmaco-economic analysis of prescribing alternative antibiotics in patients with a diagnostic label of 'penicillin allergy' and assess whether collation of information from a structured history and liaison with the family physician could reduce costs.A prospective pro-forma-based interview of randomly selected in-patients and their family physician was used to assess the validity of the diagnostic label of 'penicillin allergy'. Cost analysis of prescription of alternative antibiotics was performed and compared with first-line agents.102 patients were assessed and only 40% (n=41) were found to have a history consistent with penicillin hypersensitivity, 40% (n=41) were likely 'not allergic' and 20% (n=20) had 'indeterminate' reactions. Total cost of antibiotics prescribed for patients with penicillin allergy was 1.82-2.58-fold higher than for first-line antibiotics.Obtaining a structured history from the patient and family physician alone can enable an accurate identification of penicillin allergy status. Total acquisition cost of second-line antibiotics is higher than if these patients were prescribed first-line antibiotics.
- Predictive significance of absolute lymphocyte count and morphology in adults with a new onset peripheral blood lymphocytosis. [JOURNAL ARTICLE]
- J Clin Pathol 2014 Sep 1.
Lymphocytosis is commonly encountered in the haematology laboratory. Evaluation of blood films is an important screening tool for differentiating between reactive and malignant processes. The optimal lymphocyte number to trigger morphological evaluation of the smear has not been well defined in the literature. Likewise, the significance of lymphocyte morphology has not been well studied and there are no consensus guidelines or follow-up recommendations available. We attempt to evaluate the significance of lymphocyte morphology and to define the best possible cut-off value of absolute lymphocyte count for morphology review.71 adult patients with newly detected lymphocytosis of 5.0×10(9)/L or more were categorised to either a reactive process or a lymphoproliferative disorder. We performed statistical analysis and morphology review to compare the difference in age, gender, lymphocyte count and morphological features between the two groups. Receiver operating characteristic analysis was performed to determine an optimal lymphocyte number to trigger morphology review.Lymphoproliferative disorders are associated with advanced age and higher lymphocyte count. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of lymphocyte morphology as a screening test were 0.9, 0.59, 0.60, 0.58 and 0.71, respectively. The optimal cut-off of lymphocyte number for morphology review was found to be close to 7×10(9)/L.We found a moderate interobserver agreement for the morphological assessment. 'Reactive' morphology was very predictive of a reactive process, but 'malignant' morphology was a poor predictor of a lymphoproliferative disorder.
- Non-adenomatous forms of gastro-oesophageal epithelial dysplasia: an under-recognised entity? [REVIEW]
- J Clin Pathol 2014 Sep 1.
Foveolar dysplasia is an uncommon form of dysplasia that is encountered in the stomach and oesophagus in the context of Barrett's oesophagus. Glands displaying foveolar dysplasia also show architectural abnormalities that are similar to those encountered in adenomatous dysplasia. However, from a cytological point of view, foveolar dysplasia glands are lined by low-cuboidal to columnar epithelium, the cytoplasm is often clear with round-to-oval nuclei. Nuclear stratification as seen in adenomatous dysplasia is not common, although there is loss of nuclear polarity, pleomorphism and mitotic activity. It is important to distinguish low-grade foveolar dysplasia from regenerative change.