Usefulness of a scoring system in the interpretation of histology in neonatal cholestasis.

A 7-feature, 15-point histological scoring system had good diagnostic accuracy in the interpretation of liver histology in neonatal cholestasis

A comparison of 1995 WHO classification with 2003 ISN/RPS classification of lupus nephritis: a single centre observation

Background: In the past, lupus nephritis was histologically classified according to the 1995 WHO Classification. With the introduction of the 2003 ISN/RPS Classification, many nephropathology services converted to this new classification. This study was undertaken to compare both classification systems in a single centre practice. Methods: 103 consecutive adequate renal biopsies initially reported as lupus nephritis in the Department of Pathology, Faculty of Medicine, University of Malaya were reassessed using the criteria of both the 1995 WHO Classification and the 2003 ISN/RPS Classification. Results: The relative prevalence for each class using the WHO Classification were: Class I (1%), Class II (8.7%), Class III (6.8%), Class IV (60.2%), Class V (20.4%), Class VI (2.9%) while the prevalence using the 2003 ISN/RPS Classification were: Class I (1%), Class II (8.7%), Class III (6.8%), Class IV (61.2%), Class V (21.3%), Class VI (1%). Both classifications were essentially comparable with regards to Classes I, II and III. The differences in Classes IV, V and VI were significant in potential to alter patient management. The identification of segmental lesions (Class IV-S) over and above a global nephritis (Class IV-G) deserves more focused clinicopathological studies to gauge whether these groups have different clinical manifestations and outcomes. With regards Class V, the ISN/RPS system, by requiring that all mixed classes be stipulated in the diagnostic line, minimizes the chances of patients missing out on additional treatment. The ISN/RPS system has stricter criteria for Class VI, which again minimizes patients missing out on therapy. On the whole, the ISN/RPS system is more user-friendly as criteria are more clearly defined which translates to more benefits to patient care

Telomerase Activation in Neoplastic Cell Immortalization and Tumour Progression

The unique ability of tumour cells to proliferate indefinitely is crucial to neoplastic progression as it allows these cells to express the aggressive properties of cancer without the censure of physiological ageing. This is in contrast to normal somatic cells which are subject to a “mitotic clock,” a phenomenon that has been linked to telomeric shortening after each round of cell replication, so that eventually the loss of genetic material reaches a critical stage and the cells undergo senescence and cell death. A study was conducted to investigate the role of telomerase, an RNA-containing enzyme that restores the telomere length, in the neoplastic cell immortalization and progression process. Fresh human tissue samples taken from excision specimens received by the Department of Pathology, University of Malaya Medical Centre, were investigated for telomerase activity using a commercial Telomerase PCR-ELISA kit (Boehringer Mannheim). Specimens comprised 33 breast lesions (10 infiltrating breast adenocarcinoma, 13 fibroadenoma and 10 non-neoplastic breast tissue), 27 colonic lesions (17 colonic adenocarcinoma and 10 non neoplastic colonic mucosa) and 42 cervical lesions (20 cervical carcinoma and 22 non neoplastic cervical tissues). Telomerase activity was found in 6 (60%) of 10 breast carcinomas, 6 (46%) of 13 fibroadenomas, none of the 10 nonneoplastic breast samples, 3 (17.6%) of 17 colon carcinomas and none of the 10 non-neoplastic colonic mucosal samples, 12 (60%) of 20 cervical carcinoma and 3 (13.6%) of 22 non-neoplastic cervical samples. 5/10 (50%) Stage I, 4/7 (57%) Stage II, 2/2 (100%) Stage III and 1/1 (100%) Stage IV cervical carcinomas showed telomerase activity. These findings support a contributory role for telomerase in tumourigenesis with activation occurring from neoplastic transformation and increasing with tumour progression

Scientific misconduct encountered by APAME journals: an online survey

In June 2015, invitations were sent by email to 151 APAME journals to participate in an online survey with an objective of gaining insight into the common publication misconduct encountered by APAME editors. The survey, conducted through SurveyMonkey over a 20-day-period, comprised 10 questions with expansions to allow anecdotes limited to 400 characters, estimated to take less than 10 minutes to complete. Only one invitation was issued per journal, targeting (in order of priority) editors, editorial board members and editorial staff, and limited by email availability. 54 (36%) journals responded. 98% of respondents held Editor or Editorial Board positions. All respondent journals have editorial policies on publication ethics and 96% provide instructions related to ethics. 45% use anti-plagiarism software to screen manuscripts, the most popular being iThenticate, CrossCheck and Turnitin. Up to 50% of journals had encountered studies without IRB approval. Author misconduct encountered were (in rank order): plagiarism (75%), duplicate publication (58%), unjustified authorship (39%), authorship disputes (33%), data falsification (29%), data/image manipulation (27%), conflict of interest (25%), copyright violation (17%) and breach of confidentiality (10%). Reviewer misconduct encountered were: conflict of interest (19%), plagiarism (17%), obstructive behavior (17%), abusive language (13%) and breach of confidentiality (13%). Notwithstanding the limitations of the survey and the response rate, a few insights have been gained: (1) the need for strengthening the ethical culture of researchers/authors and reviewers, (2) anti-plagiarism software can improve plagiarism detection by about 15%, and (3) the need for technical support to detect plagiarism, duplicate publication and image manipulation

Human papillomavirus in cervical cancers of Malaysians

With a cervical carcinoma remaining the second leading cancer among Malaysian women, it is imperative to clarify the prevalence of human papillomavirus (HPV)in this respect, considering the death of local information

alpha 1-Antitrypsin deficiency is not an important cause of childhood liver diseases in a multi-ethnic Southeast Asian population

Aim: We conducted a prospective study to determine the role of alpha 1-antitrypsin (alpha 1AT) deficiency in the pathogenesis of neonatal cholestasis and other childhood liver diseases in a multi-ethnic Southeast Asian population. Methods: Prospective patients with neonatal cholestasis (group 1), other liver diseases (group 2) and children with other medical conditions (group 3) referred to the Paediatric Unit, University of Malaya Medical Centre, Malaysia, from May 2002 to June 2005, were screened for alpha 1AT level and phenotype. alpha 1AT level below 80 mg/dL was considered as low. Results: Of the 114 patients (group 1, n = 53; group 2, n = 42; group 3, n = 19) screened, seven patients (6 of total; group 1, n = 1; group 2, n = 4; group 3, n = 2) had a alpha 1AT level below 80 mg/dL. All had marginally low level (range 57-79 mg/dL), but none had a clinical diagnosis of alpha 1AT deficiency. One patient had PiZ- heterozygous phenotype (alpha 1AT level 217 mg/dL) while another patient had PiMS heterozygous. Conclusions: alpha 1AT deficiency is not an important cause of neonatal cholestasis and childhood liver diseases in Malaysian children. In Malaysian children with neonatal cholestasis or other liver diseases, routine assay for alpha 1AT phenotype is not recommended if there is no family history of neonatal cholestasis of uncertain aetiology, or if alpha 1AT level is above 80 mg/dL

Proliferating cell nuclear antigen (PCNA) activity in hepatocellular carcinoma, benign peri-neoplastic and normal liver

Hepatocellular carcinoma (HCC) is among the ten most common cancers in Malaysian males. As cellular proliferation is an important feature of malignant transformation, we studied the proliferation pattern of normal and benign perineoplastic liver versus hepatocellular carcinoma in an attempt to further understand the tumour transformation process. 39 HCC (21 with accompanying and 18 without cirrhosis) histologically diagnosed at the Department of Pathology, University of Malaya Medical Centre between January 1992 and December 2003 were immunohistochemically studied using a monoclonal antibody to PCNA (Clone PC10: Dako). 20 livers from cases who had succumbed to traumatic injuries served as normal liver controls (NL). PCNA labeling index (PCNA-LI) was determined by counting the number of immunopositive cells in 1000 contiguous HCC, benign cirrhotic perineoplastic liver (BLC), benign perineoplastic non-cirrhotic (BLNC) and NL cells and conversion to a percentage. The PCNA-LI was also expressed as Ojanguren et al’s grades. PCNA was expressed in 10% NL, 38.9% BLNC, 76.2% BLC and 71.8% HCC with BLNC, BLC and HCC showing significantly increased (p<0.05) number of cases which expressed PCNA compared with NL. The number of BLC which expressed PCNA was also significantly increased compared with BLNC. PCNA-LI ranged from 0-2.0% (mean=0.2%) in NL, 0-2.0% (mean=0.3%) in BLNC, 0-3.6% (mean=0.7%) in BLC and 0-53.8% (mean=7.6%) in HCC with PCNA-LI significantly increased (p<0.05) only in HCC compared with BLC, BLNC and NL. Accordingly, all NL, BLC and BLNC showed minimal (<5% cells being immunopositive) immunoreactivity on Ojanguren et al’s grading system and only HCC demonstrated immunoreactivity which ranged up to grade 3 (75% of cells). From this study, there appears to be a generally increasing trend of proliferative activity from NL to BLNC to BLC and HCC. Nonetheless, BLNC and BLC, like NL, retained low PCNA-LI and only HCC had a significantly increased PCNA-LI compared with the benign categories. This is probably related to the malignant nature of HCC and may reflect the uncontrolled proliferation of the neoplastic hepatocytes

Outcome of biliary atresia in Malaysia: a single-centre study

This study aimed to determine the outcome of the operation of children with biliary atresia (BA) at a tertiary paediatric referral centre in Malaysia. A prospective study on all patients with BA referred to the University of Malaya Medical Centre (UMMC), Kuala Lumpur, from 1996 to 2005 was conducted. Survival with native liver, liver transplantation (LT) or death at 2 years of age was determined. The median age at referral of the 57 patients with BA seen at University of Malaya Medical Centre was 62 days. Kasai procedure was not performed in nine patients who were all referred late (median age of referral 180 days). The median age at hepatoportoenterostomy (HPE) of the remaining 48 patients was 70 days. A total of 53 (93) patients had type 3 BA, while only 1 (2) patient had BA splenic malformation. At 2 years, the survival rate with native liver for the 48 patients who had HPE was 37, while the overall survival (native liver and LT) rate was 40. Two of the four patients who had LT survived with a liver graft at 2 years. The 2-year survival with native liver following corrective surgery for BA in UMMC, Malaysia, compares favourably with other international figures, but the overall survival rate was adversely affected by a lack of timely LT. The outcome of BA in Malaysia may be further improved by increasing the awareness among child-health professionals on the importance early referral for appropriate surgery in infants suspected of having BA

Aberrant expression of acute-phase reactant proteins in sera and breast lesions of patients with malignant and benign breast tumors

We have analyzed unfractionated sera of newly diagnosed patients (n =10) with breast carcinoma (BC), prior to treatment, and patients (n = 5) with fibrocystic disease of the breast (FDB) by two-dimensional gel electrophoresis (2-DE) and silver staining. The patients' 2-DE serum protein profiles obtained were then subjected to image analysis and compared to similar data generated from sera of normal healthy female controls (n = 10) of the same range of age. The relative expression of alpha(1)-antichymotrypsin (ACT), clusterin, and complement factor B was significantly higher in all BC patients as compared to normal controls. However, the expression of alpha(1)-antitrypsin (AAT) in 4 BC patients was apparently lower than that of the controls. Similar differential expression of ACT was detected in the FDB patients. The aberrant expression of the serum acute-phase proteins of patients with BC and FDB was confirmed by competitive enzyme-linked immunosorbent assay (ELISA). Similar altered proteins expression was also observed from immunohistochemical studies of malignant (n = 5) and benign (n = 5) breast lesions of the respective patients performed using antisera to the aberrantly expressed proteins. However, the malignant breast lesions were instead positively stained for AAT The differential expression of the serum proteins was apparently abrogated when a six-month follow-up study was performed on nine of the BC patients subsequent to treatment