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Biomedical subjects

A R Chang

Publications and source records attributed to A R Chang.

At least 19 recordsLinked to original sources

Rapid diagnosis of Penicillium marneffei infection by fine needle aspiration cytology.

This report describes the use of fine needle aspiration (FNA) cytology to make a rapid diagnosis of Penicillium marneffei infection in an HIV positive patient. P marneffei is a thermally dimorphic fungus that is a mould at 25 degrees C and a yeast at 37 degrees C. It multiplies by fission. It can be easily mistaken for various other infections that are characterised by the presence of histiocytes with phagocytosed yeast cells. In smears the demonstration of yeast cells with a distinctive central septum confirms the diagnosis.

AIDS-Related Opportunistic Infections↗

The pivotal role of the pathology laboratory in the context of a Singapore cervical cancer screening programme.

Singapore is poised to implement a national cervical screening programme and pathology laboratories have a pivotal role to play. This review describes the laboratory examination of Pap smears and the importance of providing a first class service. This will require sufficient experienced cyto-technologists and pathologists. There also needs to be a mechanism in place to monitor all stages of the Pap smear, from the time it is taken until it is reported. The Bethesda System for reporting Pap smears, new smear collection devices, liquid-based specimens, use of computer screening and other measures to enhance laboratory standards, are also discussed.

Female↗

The use of brush cytology and directed biopsies for the detection of nasopharyngeal carcinoma and precursor lesions.

BACKGROUND: It has been proposed that nasopharyngeal carcinoma (NPC) has an early noninvasive stage, designated nasopharyngeal intraepithelial neoplasia (NPIN). Hence, the detection and treatment of NPIN will prevent NPC from developing, and this would be similar to the strategies used for cervical cancer prevention. We wanted to ascertain the feasibility of using a brush sampler to collect cells for the cytologic diagnosis of NPIN and NPC. If successful, the technique could be used as a screening test in endemic areas. METHODS: A disposable sampler (Uterobrush) was used to collect nasopharyngeal mucosal brushings from 546 patients for cytologic examination. After this, most patients had biopsies, and this allowed histologic-cytologic correlation to be undertaken. RESULTS: In 528 patients (96.7%) there were satisfactory cytologic and biopsy specimens for evaluation. There were 149 cases with positive histology and 103 had positive cytology (specificity was 100% and the sensitivity was 69.1%). One case of NPC with concurrent NPIN was seen among the biopsy specimens, but no case of NPIN was detected cytologically. CONCLUSIONS: The cytologic pickup of NPC was substantially lower than that obtained on biopsy. More importantly, NPIN was uncommon. Therefore, a screening test that depends on the collection of cells for the microscopic diagnosis of NPIN and NPC is unlikely to have a major impact on the incidence of NPC. Furthermore, obtaining a good cytologic specimen from the nasopharynx is not simple, and this further limits this technique for mass screening purposes. The concept of a cytologic test for NPC, similar to the Pap test for the prevention of uterine cervix cancer, has still to be realized.

Adult↗

Concurrent hypermethylation of multiple genes is associated with grade of oligodendroglial tumors.

Current evidence suggests that epigenetic changes play an important role in the evolution of human cancers. In this study, we evaluated whether hypermethylation of CpG islands at the gene promotor regions of several tumor-related genes is involved in the carcinogenesis of oligodendroglial tumors. We examined the methylation status of 11 genes in a series of 43 oligodendroglial tumors (19 oligodendrogliomas, 13 anaplastic oligodendrogliomas, 9 oligoastrocytomas, and 2 anaplastic oligoastrocytomas) by methylation-specific polymerase chain reaction. Our results showed that hypermethylation of CpG islands was detectable in 8 of 11 genes studied and 74% of tumors were hypermethylated in at least 1 gene. Promotor hypermethylations were detected in O6-methylguanine-DNA methyltransferase (MGMT), RB1, estrogen receptor, p73, p16INK4a, death-associated protein kinase, p15INK4b, and p14ARF at 60%, 34%, 30%, 16%, 12%, 10%, 7%, and 2%, respectively. No hypermethylation was detected in the promotors of glutathione-S-transferase P1, von Hippel-Lindau or the DNA mismatch repair (hMLH1) genes. Statistical analysis revealed that concordant hypermethylation of at least 2 genes, p16INK4a and p15INK4b were significantly associated with anaplastic oligodendroglial tumors, and hypermethylation of MGMT was significantly associated with loss of chromosome 19q and with combined loss of chromosomes 1p and 19q. More importantly, several candidate tumor suppressor genes such as p16INK4a, p15INK4b, and p73 that were previously reported as unmutated in oligodendroglial tumors were found to be hypermethylated in their CpG islands. Taken together, we conclude that hypermethylation of CpG islands is a common epigenetic event that is associated with the development of oligodendroglial tumors.

Astrocytoma↗

Identification of novel regions of allelic loss in ependymomas by high-resolution allelotyping with 384 microsatellite markers.

OBJECT: Ependymomas are rare glial neoplasms; little is known about the molecular pathogenesis of this tumor entity. In a previous study the authors found multiple genomic imbalances in ependymomas resected in 20 adults and eight children, including loss of chromosomes 1p, 6, 16, 17, 19q, 20q, and 22q, as well as gain of chromosomes 4q, 5q, 7q, 9q, and 12q on comparative genomic hybridization. The aim of this study was to map in more detail the commonly affected regions in ependymomas. METHODS: A comprehensive allelotype analysis of 16 ependymomas was conducted using 384 microsatellite markers that span the 22 autosomes. Based on this high-resolution loss of heterozygosity analysis, multiple overlapping deletion regions were identified as follows: 6q25.2-27, 16p12-13.1, 16q22.3-24.1, 17q22-24, 19q12-13.2, 20q13.2-13.3, and 22q13.1-13.3. CONCLUSIONS: These data confirmed previous reports that loss of chromosomes 17 and 22 were common in ependymomas. Moreover, the authors were able to identify loss of chromosomes 13, 16, 19, and 20 as novel findings in ependymomas. It is believed that potential tumor suppressor genes that reside in these commonly deleted regions may contribute to the molecular tumorigenesis of ependymomas.

Adolescent↗

Roles of DNA cytometry and detection of EBERs in predicting a diagnosis of nasopharyngeal carcinoma.

OBJECTIVE: To analyze the suitability of DNA cytometry and detection of Epstein-Barr virus (EBV)-encoded RNAs (EBERs) on nasopharyngeal brushings for predicting a diagnosis of nasopharyngeal carcinoma (NPC). STUDY DESIGN: Cytologic preparations in 66 cases suspicious for NPC were evaluated for NPC diagnosis in comparison with the histologic diagnosis. Based on cytologic examination, 38 cases containing cytologically proven cancer and 8 cases interpreted as cytologically negative for cancer with adequate cellularity in the smear specimens were analyzed for DNA ploidy with an image analyzer and for EBER expression by in situ hybridization (ISH). RESULTS: Based on the cytologic diagnosis, DNA aneuploidy analysis, DNA nondiploidy analysis and EBER detection demonstrated a sensitivity of 50%, 84% and 92%, respectively, with the same specificity, 100%, for predicting a diagnosis of cancer. Their negative predictive values were 30%, 57% and 73%, respectively. There was a significant difference between DNA aneuploidy analysis and EBER analysis in sensitivity (P < .001) and in negative predictive value (P < .05) but not between DNA nondiploidy analysis and EBER analysis even though EBER analysis showed a slightly higher value in both parameters (P > .1 and P > .5, respectively). CONCLUSION: ISH for EBERs in cytologic smears showed a role superior to that of DNA aneuploidy analysis in the diagnosis of NPC. Considering its advantages of simple experimental conditions and lower cost as compared with DNA measurement, EBER detection can play a practical and important diagnostic role in patients suspected of having primary NPC.

Adult↗

Nasopharyngeal carcinoma heterogeneity of DNA content identified on cytologic preparations.

OBJECTIVE: To evaluate tumor heterogeneity of DNA content in nasopharyngeal carcinoma (NPC) performed on cytologic specimens. STUDY DESIGN: Image cytometric analysis of DNA ploidy status of 40 NPCs was performed on nasopharyngeal brushing smears stained with the Feulgen method after hematoxylin eosin staining. If the DNA distribution pattern from the same tumor exhibited diploid, aneuploid or/and tetraploid peaks or some combination of these patterns, the presence of tumor heterogeneity of DNA content was identified. RESULTS: Thirty-four cases (85%) had a nondiploid DNA pattern among the 40 NPCs. Twenty-eight cases exhibited tumor heterogeneity of DNA content (70%). Of the 28 tumors, 13 (46%) had a combination of diploid and tetraploid patterns, 10 (37%) had a combination of diploid and aneuploid patterns, 3 cases (11%) had a combination of tetraploid and aneuploid patterns, and 2 cases had two aneuploid stem lines. The relationship between DNA ploidy pattern and tumor histologic and cytologic morphology was also examined. CONCLUSION: There is a high incidence of DNA content heterogeneity in NPC. The relevance of tumor heterogeneity to the biologic behavior of NPC awaits further study. DNA quantification with image cytometry on destained cytologic preparations is feasible and reliable.

Aneuploidy↗

Intrathyroidal lymphoepithelial (branchial) cyst: sonographic features of a rare lesion.

Intrathyroidal lymphoepithelial cysts are rare, and only 15 such cases have been reported. Although sonography has been performed in some cases, the findings have not been discussed previously. Despite its rarity, the sonographic appearances of this lesion are similar to those of other commonly encountered congenital cystic lesions in the head and neck, such as thyroglossal duct cysts and second branchial cleft cysts, and this may provide a clue to its diagnosis. We describe the sonographic appearances of intrathyroidal lymphoepithelial cysts.

Biopsy, Needle↗

The cervical smear test in the next millennium.

This paper traces the cervical Papanicolaou smear test from the seminal work of George Papanicolaou undertaken more than 70 years ago, to the present use of computer technology to examine cervical smears. However, to successfully detect cervical cancer and precursor lesions, the standard of the specimens, as well as that of the screening laboratory, must be of the highest order so that false negative results are eliminated. Newer sampling devices, techniques for improving specimen quality, computerised laboratory technology, and the need for laboratory accreditation are also discussed. The Papanicolaou test is the most successful test invented for cancer prevention but despite this, up to two thirds of Hong Kong women have not had a test. There is a need for more public health education directed at women so that there is a greater awareness of the importance of disease prevention, with an emphasis on cancer prevention. The implementation of a cervical screening programme in the new millennium will ensure that women receive all the benefits that the Papanicolaou smear test can confer.

Journal Article↗

Assessment of proliferating cell nuclear antigen in nasopharyngeal carcinoma tissue and its relation to clinical findings.

47 newly diagnosed patients with nasopharyngeal carcinoma (NPC) were studied using the proliferating cell nuclear antigen (PCNA) immunostaining technique. The results were reproducible as shown by assessment of three separate sections performed for each patient. No statistical correlation was found between PCNA labelling index (LI) and Ho's clinical staging or time required to achieve complete remission of the local disease. A higher PCNA LI was associated with a poorer disease-free survival. The literature on the use of PCNA in human tumours is reviewed.

Adolescent↗

In vitro uptake of bromodeoxyuridine by human nasopharyngeal carcinoma (NPC) and its relation to clinical findings.

A cell kinetic study of 27 newly diagnosed patients with nasopharyngeal carcinoma (NPC) using the in vitro bromodeoxyuridine (BrdU) technique was performed. The results were reproducible as demonstrated by three independent sections performed on each patient. No correlation between BrdU labelling index (LI) and Ho's clinical staging was found. A higher LI was associated with the development of distant metastases (P = 0.057). Statistically significant correlation was found between low LI and longer duration required to achieve complete remission in the primary site of disease (P = 0.026). This study suggests a potential role for in vitro BrdU labelling index as a prognosticator for NPC prior to treatment.

Adult↗

Primary mediastinal malignant germ cell tumour. Single institution experience in Chinese patients and correlation with specific alpha-fetoprotein bends.

Ten Chinese patients were reviewed, all with mediastinal germ cell tumours and treated in our centre during the past 8 years. Three patients with pure seminomas were given chemotherapy with or without radiotherapy. AB achieved complete remission with no relapse. Seven patients with non-seminomatous germ cell tumours (NSGCT) were given chemotherapy, with or without surgery. Two patients with rapid decay of alpha-fetoprotein (AFP) levels (half-life less than or equal to 7.2 days) during chemotherapy achieved complete remission with no relapse. Five patients with prolonged decay of AFP levels (half-life > 7.2 days) failed to achieve complete remission with initial chemotherapy and all but one patient died between 5 and 9 months later. One patient developed acute megakaryocytic leukaemia. Using isoelectric focusing, AFP bands specific to NSGCT were quantified, and comparison was made with the total AFP in five cases. In each case the change in NSGCT-specific AFP concentration in response to therapy closely paralleled that of total AFP. Estimation of NSGCT-specific AFP offers no apparent advantage in monitoring disease response or progression.

Adult↗

DNA content in cervical carcinoma: a flow cytometric assessment of DNA heterogeneity.

The degree of DNA heterogeneity varies between tumors arising in different body sites. Any substantial degree of variability within a given tumor can give rise to significant problems in the interpretation of DNA flow cytometric (FCM) studies. This study was undertaken to evaluate the degree of DNA heterogeneity in cervical carcinomas. A total of 100 3-mm punch biopsies were evaluated from single large cases in 10 sections of cervical carcinoma. Of the 10 tumors, 6 were squamous carcinoma, 1 was an adenocarcinoma, 1 was a mixed small cell and squamous carcinoma, 1 was an adenosquamous cancer, and 1 was a small cell carcinoma with a small area of adenocarcinoma. Adequate histograms were available for 95 (95%) of the samples. Of the 10 cases studied, 9 (90%) revealed homogeneity in the DNA pattern. A solitary case demonstrated heterogeneity in one histogram (nine samples DNA diploid and one sample DNA aneuploid). This case was predominantly small cell undifferentiated carcinoma with focal adenocarcinoma. The area of adenocarcinoma was probably the area that contributed to the heterogeneous FCM pattern. From this study we conclude that for most cervical carcinomas of a specific histologic type there is DNA homogeneity. However, for carcinomas with a mixed morphology, DNA heterogeneity is possible and this must be taken into account in any DNA ploidy studies that include mixed or combined tumors.

Adenocarcinoma↗

Some aspects of cervical screening in southern New Zealand; the situation before implementation of the national cervical cancer prevention programme.

To gain some idea of cervical screening in Otago and Southland (two southern provinces of New Zealand), before the implementation of a national cervical cancer prevention programme, a questionnaire was sent to all doctors identified as smear takers. Questionnaires were returned by 75% of the doctors. Only 53.8% of practice nurses were involved in taking smears. Well Women Clinics staffed by nurses were not widespread in either province. Just under half (46.4%) of doctors took cervical smears as part of a health check programme. Sixty-three per cent (63.3%) routinely performed a pelvic examination when taking a smear. Surprisingly few doctors were familiar with the technique of placing spatula and cytobrush samples on one slide, a manoeuvre which could significantly reduce the workload of the cytology laboratories. Only a minority of doctors were aware of a new sampler which can provide samples equivalent to combined spatular-cytobrush smears. There was confusion over the timing of a repeat smear following two normal ones. The recommended interval of 3 years was only complied with by 44.2% of doctors. However, 71.4% of respondents did remind women to have smears. The study indicates that many doctors already provide patients with a good cervical screening service, and this augers well for the national screening programme.

Adult↗

'Erosion' of the uterine cervix; an anachronism.

The conclusion arrived at after a review of the relevant literature, coupled with current knowledge of the morphophysiological changes which take place in the transformation zone of the cervix, is that the term cervical erosion is an anachronism. The term should therefore be abandoned. More appropriate terms for the clinical appearance of the cervix are ectropion or ectopy. The metaplastic process and its role in neoplasia is also discussed.

Cell Transformation, Neoplastic↗

The histopathology of biopsies taken from women attending a New Zealand colposcopy clinic.

Analysis of the histopathology of biopsies taken from 1371 women attending the Dunedin Hospital Colposcopy Clinic during the period 1982-1988 showed that CIN3, either alone or in conjunction with human papillomavirus (HPV) infection, was the most commonly encountered abnormality. Women under the age of 29 years accounted for 58.3% of the CIN3 lesions. There was also a dramatic increase in the number of women with evidence of HPV infection. Several cases of invasive carcinoma were encountered, 3 in very young women. However, there was no obvious age predilection for the various grades of CIN and for HPV lesions. This raises the question of whether or not HPVs in cervical cancer are chance associations rather than being actively involved in lesion information.

Adolescent↗