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J Clin Pathol [journal]
- The value of autopsies in the era of high-tech medicine: discrepant findings persist. [JOURNAL ARTICLE]
- J Clin Pathol 2014 Mar 4.
Although the autopsy is still the gold standard for quality assessment of clinical diagnoses, autopsy rates have been declining over the last decades to <10%. The aim of this study was to investigate the value of autopsies in the high-tech medicine era by determining the frequency of discrepancies between clinical and autopsy diagnoses.We classified all adult autopsy cases (n=460), performed at Symbiant, Pathology Expert Centre, in 2007 and 2012/2013, as having major, or minor discrepancy or total concordance. The roles of possible contributory factors were analysed. Finally, we assessed the role of microscopic examination in identifying cause of death.Major and minor discrepancies were found in 23.5% and 32.6% of the classifiable autopsies, respectively. Most commonly observed major discrepancies were myocardial infarction, pulmonary embolism and pneumonia. Improper imaging and discontinuation of active treatment were significantly associated with a higher and a lower frequency of major discrepancies, respectively. Comparing 2007 and 2012/2013, the frequency of minor discrepancies significantly increased from 26.8% to 39.3%. Final admission length of >2 days was significantly associated with a lower frequency of class III minor discrepancies. Microscopic examination contributed to establishing cause of death in 19.6% of the cases.Discrepant findings persist at autopsy, even in the era of high-tech medicine. Therefore, autopsies still should serve as a very important part of quality control in clinical diagnosis and treatment. Learning from individual and system-related diagnostic errors can aid in improving patient safety.
- Fasting increases serum bilirubin levels in clinically normal, healthy males but not females: a retrospective study from phase I clinical trial participants. [JOURNAL ARTICLE]
- J Clin Pathol 2014 Mar 4.
To examine if fasting affects serum bilirubin levels in clinically healthy males and females.We used retrospective data from phase I clinical trials where blood was collected in either a fed or fasting state at screening and predosing time points and analysed for total bilirubin levels as per standard clinical procedures. Participants were clinically healthy males (n=105) or females (n=30) aged 18-48 inclusive who participated in a phase I clinical trial in 2012 or 2013.We found a statistically significant increase in total serum bilirubin levels in fasting males as compared with non-fasting males. The fasting time correlated positively with increased bilirubin levels. The age of the healthy males did not correlate with their fasting bilirubin level. We found no correlation between fasting and bilirubin levels in clinically normal females.The recruitment and screening of volunteers for a clinical trial is a time-consuming and expensive process. This study clearly demonstrates that testing for serum bilirubin should be conducted on non-fasting male subjects. If fasting is required, then participants should not be excluded from a trial based on an elevated serum bilirubin that is deemed non-clinically significant.
- Prevalence and molecular characterisation of the sessile serrated adenoma in a subset of the Chinese population. [JOURNAL ARTICLE]
- J Clin Pathol 2014 Feb 25.
The incidence and mortality rates from right-sided colorectal cancers (CRCs) have not decreased in recent years. It is very likely that a significant proportion of these cancers evolve from undetected sessile serrated adenomas (SSAs). The prevalence and molecular features of the SSAs in the Chinese population have seldom been investigated.We retrospectively reviewed the colonoscopy database and pathology archives in our medical centre. Adenomatous polyposis coli (APC) and β-catenin expressions were examined in 28 right hyperplastic polyps (RHPs) and 21 SSAs by immunohistochemical staining. The mutations of BRAF, KRAS, APC and β-CATENIN were analysed by direct sequencing. The methylation status of APC promoter in these polyps was analysed by methylation-specific PCR and bisulfite sequencing. Samples of left hyperplastic polyps, traditional adenomas and CRC were used as controls.SSAs accounted for 4.9% of serrated polyps and 1.0% of all colorectal polyps. BRAF((V600E)) mutations were found in 14.3% of SSAs and 7.1% of RHPs. Nuclear accumulation of β-catenin was seen in 28.6% of SSAs and 17.9% of RHPs. APC mutations were detected in 57.1% of SSAs and 67.9% of RHPs. APC methylation was detected in 14.3% of RHPs and 23.8% of SSAs.The prevalence of SSAs in a subset of the Chinese population is much lower than that in the Western population. BRAF((V600E)) mutation is not a frequent event in right colon serrated polyps in a subset of the Chinese population. APC mutation is possibly the main cause for the Wnt signalling activation in right colon serrated polyps.
- A survey of reporting of colorectal cancer in Scotland: compliance with guidelines and effect of proforma reporting. [JOURNAL ARTICLE]
- J Clin Pathol 2014 Feb 24.
The main purpose of the study was to present a baseline audit of reporting of colorectal cancers resection specimens in Scotland, audited against the Royal College of Pathologists (RCPath) standards (2007) and NHS Quality Improvement Scotland (NHS QIS) standards.50 consecutive rectal and 50 consecutive colonic cancer cases from 2011 were audited from 10 Scottish health boards involved in colorectal cancer reporting (n=953). The rates of reporting of serosal involvement, extramural venous invasion (EMVI) and the mean numbers of lymph nodes found were audited against RCPath standards and compared between units that routinely used a reporting proforma versus those that did not.The performance in reporting of rectal cancer was generally worse than for colonic cancer, with only three units meeting the RCPath standards for reporting of rectal cancer. There were significant differences between units that routinely used a proforma, with the non-proforma group failing to meet the minimum standards for both serosal involvement (6%) and EMVI (24%). In the non-proforma group, 56% of rectal cases had a mean lymph node count of 12 or more compared with 81% in the proforma group.Significant differences exist in the frequencies with which important adverse prognostic features are reported by pathologists across 10 Scottish health boards. This has potential implications for patient care. Health boards that make routine use of reporting proformas are more likely to meet RCPath guidelines for reporting of these important pathological parameters.
- Expression of growth arrest-specific protein 6 and Axl molecules in the left internal mammary artery of patients undergoing coronary artery bypass grafting. [JOURNAL ARTICLE]
- J Clin Pathol 2014 Feb 24.
Studies have demonstrated that using a left internal mammary artery (LIMA) graft yields excellent long-term results in coronary artery bypass grafting (CABG). The growth arrest-specific 6 (Gas6) gene and its receptor, Axl, are crucial in vascular haemostasis and atherosclerosis. The objective of this study was to determine the expression of Gas6 and Axl molecules in the aorta and LIMA in patients undergoing CABG.Plasma and tissue specimens were collected from 19 patients undergoing elective CABG. The expression of the Gas6 and Axl in the injured aorta and LIMA was examined using reverse transcription PCR (RT-PCR), real-time RT-PCR, western blot and immunohistochemical staining.In CABG patients, the mRNA, immunoreactivity and protein expressions of the Gas6 and Axl were considerably higher in the LIMA than those in the aorta. Further analysis revealed that the expression of the Gas6 positively correlated with that of Axl in the LIMA and aorta. The plasma Gas6 level was considerably and positively correlated with the expression of Gas6 protein in the LIMA and aorta.The present study discovered that the higher expression of Gas6/Axl pathway components in the LIMA compared with that in the aorta may partly explain the less frequent atherosclerotic events involving the LIMA compared with other arteries. Moreover, Gas6 may play a critical and protective role in human vascular biology.
- Pathology of serrated colorectal lesions. [JOURNAL ARTICLE]
- J Clin Pathol 2014 Feb 21.
The concept of serrated colorectal neoplasia has become recognised as a key process in the development of colorectal cancer (CRC) and an important alternative pathway to malignancy compared with the long-established 'adenoma-carcinoma' sequence. Increasing recognition of the morphological spectrum of serrated lesions has occurred in parallel with elucidation of the distinct molecular genetic characteristics of progression from normal mucosa, via the 'serrated pathway', to CRC. Some of these lesions can be difficult to identify at colonoscopy. Challenges for pathologists include the requirement for accurate recognition of the forms of serrated lesions that are associated with a significant risk of malignant progression and therefore the need for widely disseminated reproducible criteria for their diagnosis. Alongside this process, pathologists and endoscopists need to formulate clear guidelines for the management of patients with these lesions, particularly with respect to the optimal follow-up intervals. This review provides practical guidance for the recognition of these lesions by pathologists, a discussion of 'serrated adenocarcinoma' and an insight into the distinct molecular genetic alterations that are seen in this spectrum of lesions in comparison to those that characterise the classic 'adenoma-carcinoma' sequence.
- Remote and rapid pathological diagnosis in a resource challenged unit. [JOURNAL ARTICLE]
- J Clin Pathol 2014 Feb 21.
Malawi is one of the world's poorest countries, but despite this, has a dedicated paediatric oncology service. The service has been hampered by the inability to make a timely cytological diagnosis in the majority of patients. A telemedicine programme was commenced to help overcome this problem, and the results for the first 197 consecutive patients are described. The results are compared with the local reports where available. Most samples were fine needle aspirates (104/197-53%), but others included bone marrow aspirates, peripheral blood films and other fluid collections. A diagnosis was arrived at in 52% of the samples; there were 46 discordant results, 38 were when one or other of the local or distant teams were unable to make a diagnosis, and only 8 where the diagnoses of the 2 teams differed. Diagnoses were made and reports were compiled by the 'distant' team within 24 h and sent to the centre in Malawi. This simple telepathology initiative has had a positive impact on clinical management, and could be used in other less resourced centres twinned with better resourced ones.
- Correction. [Journal Article]
- J Clin Pathol 2014 Mar; 67(3):288.
- Comprehensive analysis of clinico-pathological data reveals heterogeneous relations between atherosclerosis and cancer. [JOURNAL ARTICLE]
- J Clin Pathol 2014 Feb 11.
Atherosclerosis and cancer share common risk factors and involve similar molecular pathomechanisms. Most clinical and epidemiological studies show a positive correlation between atherosclerosis and smoking-related cancers and heterogeneous results for non-smoking-related cancers. However, up-to-date large-scale autopsy studies including a detailed analysis of cancer types are lacking. Therefore, we sought to investigate the relation between major cancer types and the grade of atherosclerosis in a recent well-powered autopsy cohort.In 2101 patients, both autopsy data and clinical data including demographics, disease groups, tumour type, cause of death and grade of atherosclerosis were reviewed and statistically analysed.We found cancer in general is associated with less atherosclerosis (OR 0.60, p<0.0001). In particular, haematological neoplasm and sarcomas were associated with much less atherosclerosis (OR=0.45, p<0.0001 and OR=0.43, p=0.087), while carcinomas were associated with moderately less atherosclerosis (OR=0.72, p=0.002). Furthermore, non-smoking-related cancers were associated with much less atherosclerosis (OR=0.41, p<0.0001), while possibly smoking-related cancer and smoking-related cancer showed no significant association. In a comprehensive analysis of 21 cancer types, biliary tract cancer, lymphomas/lymphoid leukaemias and kidney cancer were associated with much less atherosclerosis (OR=0.19, p<0.0001; OR=0.41, p<0.0001; and OR=0.48, p=0.029). In an exploratory analysis of treatment strategies, we found that tumours with a recommendation of oxazaphosphorines and pyrimidine antagonist treatment were significantly associated with less atherosclerosis (OR=0.33, p=0.0068 and OR=0.58, p=0.012).In conclusion, the study showed an inverse association between cancer and atherosclerosis postmortem that depends on the cancer type and suggests a possible impact of chemotherapy regimens.
- Lymph node revealing solutions in colorectal cancer: should they be used routinely? [JOURNAL ARTICLE]
- J Clin Pathol 2014 Feb 3.
The Royal College of Pathologists (RCPath) and College of American Pathologists recommend that at least 12 lymph nodes should be harvested for adequate staging of colorectal carcinoma. Just one nodal tumour deposit upstages the malignancy from pN0 to pN1. This is critically important as node-positive patients (pN1) are considered for adjuvant chemotherapy whereas node-negative patients (pN0) may not be. It is not always easy to harvest the required number, especially in patients with rectal carcinoma who may have received neoadjuvant therapy-an increasingly common treatment. The use of neoadjuvant therapy is known to further decrease the number and size of identifiable lymph nodes within specimens, meaning that the lymph node harvest often fails to reach RCPath guidelines. Lymph node revealing solutions consisting of either single chemicals such as alcohol or acetone or compounds have been investigated to help improve the lymph node harvest in difficult specimens, for example, those received following neoadjuvant therapy. Published research evidence reviewed here suggests that lymph node revealing solutions significantly improve lymph node harvesting, and that glacial acetic acid, ethanol, water and formalin is advantageous in comparison with other revealing solutions in that it is safe, cheap, easy to use and relatively quick. However, the quantity of good evidence is limited and the clinical implications of improving lymph node harvesting require further research.