Oculopharyngeal muscular dystrophy: underdiagnosed disease in Hong Kong.

Despite the advances in the understanding of the molecular basis for oculopharyngeal muscular dystrophy in the last decade, it remains an underdiagnosed disease, especially among the Chinese. In the presence of a positive family history and late-onset ptosis, dysphagia, and proximal muscle weakness (its cardinal features), we suggest that PABPN1 gene analysis should be the first-line investigation to rule out this condition. Muscle biopsy can be reserved for atypical cases. Non-specific mitochondrial changes in the muscle specimens of these patients should be appreciated, so as to avoid diagnostic confusion. It is hoped that greater awareness among medical professionals and judicious use of PABPN1 gene analysis will lead to earlier diagnosis, better management, and avoidance of unnecessary invasive investigations of affected patients.

A case of malignant pleural mesothelioma with unexpectedly long survival without active treatment.

Malignant pleural mesothelioma (MPM) is a disease with a very dismal prognosis. A median survival of 6-18 months is expected in most patients. Rarely, patients may survive unexpectedly long. We present the case of a patient with MPM who survived for more than 10 years without active treatment after the disease had been diagnosed.

Sclerosing hemangioma of lung: A close cytologic mimicker of pulmonary adenocarcinoma.

We report the fine-needle aspiration biopsy findings of sclerosing hemangioma of lung occurring in a 40-yr-old Chinese woman. Cytologically, there were hyalinized stromal tissue fragments admixed with clusters of nondescript mononuclear tumor cells. Scattered foamy macrophages and red blood cells were also noted in the background. Focal papillary and acinar configurations were seen. However, some of the epithelial cells show nuclear pleomorphism with nuclear hyperchromasia, prominent nucleoli, and occasional intranuclear inclusions. Mitotic activity was virtually absent. The cytologic atypia present may result in misdiagnosis of well-differentiated pulmonary adenocarcinoma, especially bronchioloalveolar carcinoma. Recognition of the subtle cytologic differences, together with cell block examination, immunocytochemistry, and proper clinicoradiologic correlation, is crucial for an accurate preoperative diagnosis.

Surfactant tracheobronchial lavage for the management of a rabbit model of meconium aspiration syndrome.

We evaluated the effect of tracheobronchial lavage with diluted surfactant solution (bovine lipid extract surfactant, bLES) in a rabbit model of meconium aspiration. All animals were anaesthetized, tracheotomized and given 3-4 ml/kg of 25% slurry of human meconium into the endotracheal tube and mechanically ventilated for 1 h. The animals were then randomly assigned to surfactant lavage (n = 12) with 15 ml/kg of diluted surfactant at a concentration of 5.4 mg phospholipid/ml administered in aliquots of 2 ml; or simple endotracheal suction (control n = 12) when the oxygenation index (OI) was >/=15. Changes in the arterial blood gases and the histomorphological and radiological appearances of the lungs were recorded. The OI and arterial/alveolar oxygen tension (a/A PO2) of the surfactant lavage group improved significantly at 5 min post-treatment, and these improvements were observed throughout the ensuing 4 h of ventilation. There was significantly more solid content recovered by surfactant lavage compared with the control group (p = 0.0001). Radiologically, the post-treatment air space opacification scores of the lavage group were significantly lower compared with the control (p = 0.002). The post-treatment radiographs of the lavage-treated rabbits were rated by the radiologist, who was blinded to the treatment groups, as much improved in 5 and improved in 4, whereas the control rabbits were rated as much worse in 3 and worse in 4. Histological examination showed the lungs of the lavaged rabbits had significantly more normal airway (p < 0.0001), more fields showing completely normal airspace (p = 0.0001) and less fields showing severe overdistension with meconium (p = 0.0005). We concluded that lavage with diluted surfactant solution effectively washed out the meconium, improved gases exchanges, and improved the histological and radiological appearances in the rabbit model of MAS.

The angiopoietins, tie2 and vascular endothelial growth factor are differentially expressed in the transformation of normal lung to non-small cell lung carcinomas.

The successful establishment of angiogenesis depends on a complex process of endothelial proliferation and organization. The angiopoietins (Ang-1 and Ang-2) and Tie2 ligand-receptor system is essential for the regulation of vascular maturation and stability during embryonic development. Together with the vascular endothelial growth factor (VEGF)-mediated pathway, they have been implicated in the control of normal physiological angiogenesis. We investigated their potential role and interaction in the development of lung cancers by comparing the expression pattern and inter-relationship of Ang-1 and 2, Tie2 and VEGF levels in 28 pairs of primary non-small cell lung cancers (NSCLC) and normal lung. Using semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and in-situ hybridization (ISH), we showed that in NSCLC, there was significantly up-regulated VEGF expression by the tumour cells and an increased intensity of Ang-2 expression in the tumour vessels. The number of Ang-2-expressing vessels also correlated with the grades of tumour cell expression of VEGF. On the other hand, normal lung expressed constitutively high and correlated levels of Ang-1 and Tie2, which were significantly reduced in the carcinomas. The findings suggested a role of the Ang-1/Tie2 pathway in the maintenance of the complex vasculature in normal lung, while collaborative activities between the Ang-2 and VEGF pathways might be important in promoting tumour angiogenesis in NSCLC.

p53 intron 2 genotypes detected in normal specimens and lung carcinomas in Hong Kong.

Previous studies suggest that the polymorphic p53 intron 2 displays a high frequency of mutations, occurring with different frequencies in tumor tissues versus peripheral blood of lung cancer patients as compared to healthy individuals. We evaluated the significance of these polymorphisms and mutations utilizing matched triple specimens from the lung tumor, normal lung tissue, and peripheral blood of cancer patients. Identical genotypes were observed in normal tissues and blood, while 4 mutations were observed in tumors. The A1 allelic frequency was increased in the adenocarcinoma tissues as compared to normal tissues. Two p53 exon 2 polymorphisms were detected, appearing with equal frequencies among cancer patients and healthy individuals. The p53 intron 2 polymorphic locus is a hot spot for mutations in Hong Kong lung cancer patients.

Monocyte chemoattractant protein-1 (MCP-1) expression in primary lymphoepithelioma-like carcinomas (LELCs) of the lung.

Lymphoepithelioma-like carcinoma (LELC) of the lung is a recently recognized primary non-small cell lung carcinoma with distinct clinicopathological features and an aetiological association with Epstein-Barr virus (EBV) infection. The tumour consists of clusters and sheets of poorly or undifferentiated tumour cells in close association with numerous mononuclear inflammatory cells, including a rich component of tumour-associated macrophages (TAMs). To investigate the molecular mechanism leading to the TAM-rich stroma, the expression of a monocyte-specific chemotactic and activating factor, monocyte chemoattractant protein-1 (MCP-1), was studied by reverse transcriptase-polymerase chain reaction (RT-PCR) and in situ hybridization (ISH), and the presence of TAMs was demonstrated by immunohistochemistry in nine LELCs. The results were compared with those found in 17 conventional non-small cell lung carcinomas. RT-PCR showed specific MCP-1 amplification in both LELCs and non-LELCs, but ISH demonstrated a unique and extensive expression of MCP-1 transcripts by the tumour cells of LELCs only, while TAMs, stromal fibroblasts, and endothelial cells formed the major source of MCP-1 in non-LELCs. TAMs in LELCs were more abundant and showed a close topographical relationship with the MCP-1-expressing tumour cells. The results indicate that tumour cell expression of MCP-1 in LELCs is an important mechanism contributing to their distinctive morphological features. This is the first study that demonstrates the in vivo upregulation of a monocyte-specific chemokine by EBV-related carcinomas, illustrating an interesting aspect of tumour biology in EBV-related neoplasms.

Nonsecretory immunoglobulin-derived amyloidosis of the heart: diagnosis by immunohistochemistry of the endomyocardium.

Primary amyloid light chain (AL) amyloidosis of the heart is a rare cause of congestive heart failure. Approximately 15% of patients with primary AL amyloidosis demonstrate no monoclonal proteins on serum or urine immunoelectrophoresis:(so-called nonsecretory immunoglobulin-derived amyloidosis). The histologic findings of endomyocardial biopsy from these patients may be indistinguishable from those with senile cardiac amyloidosis. However, the AL type may respond favourably to chemotherapy while the latter type does not. The prognosis is also better in the senile cardiac amyloid type. The precise diagnosis in the present case was made by applying immunohistochemical techniques on cardiac tissues.

Recurrent aortic valve prosthesis dehiscence secondary to aortoarteritis: three case reports and literature review.

We report three young Chinese male patients who underwent aortic valve replacement for severe aortic regurgitation of subacute onset, complicated by recurrent dehiscence of the aortic valve prosthesis, due to aortitis. One of the three patients underwent aortic valve replacement three times and progression of the prosthesis dehiscence was arrested with the use of corticosteroids. A review of the literature on the prognosis and treatment of aortoarteritis with particular reference to the management of recurrent valvular dehiscence is discussed.

Chromosomal 11 alterations in non-small-cell lung carcinomas in Hong Kong.

We examined 60 non-small-cell lung cancer (NSCLC) patients for evidence of genetic alterations on chromosome 11 with nine polymorphic markers by Southern blot and microsatellite marker analysis. These analyses detected genetic alterations at both the 11p and 11q arms. At the 11p15 Ha-ras locus, the loss of heterozygosity (LOH) occurred in three out of 11 (27.3%) of the informative cases; at the 11p11-q12 D11S149 locus, the LOH occurred in two out of nine (22.2%) of the informative cases; and at the 11q13 INT-2 locus, the LOH occurred in four out of 18 (22.2%) of the informative cases. Microsatellite markers in the 11q12-q13 region revealed genetic alterations for PYGM in eight out of 54 (14.8%) of the specimens studied and 10 out of 55 (18.2%) of the specimens for the INT-2 marker. The data suggest genetic alterations occur in some of the lung cancer patients in both the 11p and 11q regions.

Detection and evaluation of p53 intron 2 polymorphism in lung carcinomas in Hong Kong.

A polymorphism in intron 2 of the p53 gene, which gives rise to 2 alleles, A1 and A2, was analyzed by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and direct DNA-sequencing techniques. The distribution of this allele in the peripheral blood in the Chinese population comprising 27 healthy individuals, 30 bronchiectasis patients, 34 non-small-cell lung cancer (NSCLC) patients and 27 SCLC patients was analyzed. The genotypic distributions for this marker were significantly different between the blood of healthy individuals and SCLC patients. There was no significant difference between genotypes of Caucasians and Chinese. Tumors, normal lungs and peripheral blood of 83 adenocarcinoma and 10 squamous cell carcinoma patients were also studied. There was a significant difference in the distribution of the genotypes detected in tumor tissues vs. blood of adenocarcinoma patients. The frequency of detection of the A1/A1 genotype in the tumor tissues was increased in adenocarcinoma patients as compared with the blood of adenocarcinoma patients and was decreased in the blood of SCLC patients as compared with the blood of healthy individuals. Survival rates in Hong Kong adenocarcinoma patients with the A1/A1 genotype were lower than those in patients with A1/A2 and A2/A2 genotypes up to 30 months post-operation. Point mutations were detected at the p53 intron 2 polymorphic locus in NSCLC specimens, with a mutation rate of 15.4% (8/52). All mutations were GC transversions. The significance of this instability in p53 intron 2 remains to be elucidated.

Surgical resection of pulmonary metastases from nasopharyngeal carcinoma.

BACKGROUND: Nasopharyngeal carcinoma (NPC), unlike other head and neck cancers,is known for its propensity for distant metastases. Chemotherapy remains the mainstay of treatment because of this and the chemosensitivity of the tumour, but long-term control is rare. The surgical management of pulmonary metastases of other extrathoracic malignancies prompted this review of surgical management of patients with NPC. METHODS: Thirteen thoracotomies were performed in 12 patients with pulmonary metastases as the first and only site of relapse of nasopharyngeal carcinoma. Postoperative chemotherapy was given in four patients, radiotherapy to the mediastinum in one patient and both chemotherapy and radiotherapy in two patients. The survival pattern of this group of 12 patients was compared with a historical control group consisting of 65 patients without surgical resection. RESULTS: Lymph node involvement was documented in four patients during operation. Four patients relapsed after surgical resection, two of them were from the group of three patients with lymph node involvement. The site of subsequent relapse was the lung for three patients and the skeletal system for the fourth. The 2 year actuarial survival of the surgically resected group compared favourably with the historical control group (80% and 24.1%, respectively; P=0.0002 by Mantel-Cox text). CONCLUSIONS: Surgical resection of pulmonary metastases from NPC seems to be a promising approach thought the effect of case selection cannot be excluded and further studies are indicated. The importance of exploration and dissection of mediastinal nodes in the surgical management of pulmonary metastases from NPC was demonstrated.

In situ detection of Epstein-Barr virus in non-small cell lung carcinomas.

Epstein-Barr virus (EBV) is strongly associated with nasopharyngeal carcinoma and lymphoepithelioma-like carcinomas (LELC) of foregut-derived organs. Recently this group of EBV-associated carcinomas has been expanded by the identification of the virus in conventional adenocarcinomas of the stomach. In situ hybridization (ISH) using a sensitive digoxigenin-labelled EBER RNA probe was performed on 167 consecutive unselected primary non-small cell lung carcinomas, to determine the frequency of EBV association in these tumours. Nine cases (5.4 per cent) showed strong EBER signals in the tumour cell nuclei. By immunohistochemistry, four of the EBER-positive tumours showed patchy expression of the viral latent membrane protein (LMP-1) and none showed any expression of the EBV nuclear antigen 2 (EBNA2). Morphologically, all the positive tumours were LELC, whereas no conventional type of non-small cell lung carcinoma showed EBV association. The LELC presented a morphological spectrum from undifferentiated to squamoid or glandular differentiation. The patients showed a male to female ratio of 8:1. The mean age at presentation was 48 years. Smoking was not a risk factor. All patients were alive at follow-up periods of 23-52 months. Southern blot analysis performed on eight of the nine positive tumours showed a clonal episomal form of EBV, suggesting the clonal expansion of an infected tumour cell early in oncogenesis. These characteristics of the EBV-associated lung tumours justify their consideration as a distinct clinicopathological entity.

Evaluation of a histogenetic classification for thymic epithelial tumours.

We reviewed 87 thymic epithelial tumours from Chinese patients and typed them according to the Marino and Müller-Hermelink classification as updated by Kirschner and Müller-Hermelink in 1989. Related categories were grouped for statistical analyses: group 1, medullary thymoma and mixed thymoma; group 2, cortical predominant thymoma; group 3, cortical thymoma and well-differentiated thymic carcinoma; group 4, other thymic carcinomas; and group 5, unclassified. Group 3 tumours were more frequently associated with the myasthenia gravis syndrome compared with group 1 tumours (P = 0.001). They also presented at a more advanced stage. Groups 1 and 2 showed an excellent prognosis (100% survival at 10 years). The 10-year survival for groups 3 and 4 patients was 40% and 30% respectively. Pure medullary thymoma made up a higher proportion of our cases (10.3%) than those of a similar Caucasian study (5.3%). The eight thymic carcinomas (group 4) included two thymic lymphoepitheliomas. We conclude that the histogenetic classification evaluated shows a clear correlation with prognosis and clinical features, even when tested on separate geographic groups, where pathogenetic factors may be different. A common approach to classification of thymic epithelial tumours would greatly facilitate future studies on these possible differences.

Disseminated mediastinal carcinoma with chromosomal translocation (15;19). A distinctive clinicopathologic syndrome.

BACKGROUND: A case of disseminated mediastinal carcinoma probably of thymic origin is reported in a 5-year-old boy with an anterior mediastinal mass associated with superior vena cava obstruction, tracheal deviation, right malignant pleural effusion, and evidence of bone metastasis. The diagnosis was based on findings of radiologic localization, light and electron microscopic study, and immunohistochemistry. The patient received combination chemotherapy but died of progressive disease. METHODS: Cytogenic study on the pleural fluid was attempted, and a literature search for similar chromosomal aberration was performed. RESULTS: Cytogenetic study of tumor cells from the pleural fluid revealed a clonal chromosomal abnormality of t(15;19)(q12;p13.1). Two patients with similar disease were reported in the English literature; their clinical courses, immunohistochemical findings, and t(15;19) were almost identical to those of the patient reported in this study. CONCLUSION: The authors suggest that this translocation may be specific to thymic carcinoma and may indicate a particularly aggressive form of the disease. Carcinomas are rare in children, so the chromosomal translocation may serve as a helpful marker for the diagnosis.

Effect of percutaneous balloon mitral valvuloplasty on serum creatinine phosphokinase MB-isoenzyme levels.

Twenty-one patients with moderate to severe mitral stenosis were treated with percutaneous balloon mitral valvuloplasty (PBMV) using Inoue mitral double-lumen balloon catheters. Creatinine phosphokinase MB isoenzyme (CPK-MB) levels were measured at baseline, 5 min, 6 h, and 18 h post dilatation. Haemodynamic indexes, 12-lead ECGs, and 2-dimensional echocardiograms were performed to evaluate systolic function postprocedure. CPK-MB levels were modestly increased at 5 min and at 6 h postprocedure compared with the baseline level (p < 0.001) but were still within the normal reference range, except for one patient who had a level at 5 min minimally above the upper limit of normal. CPK-MB levels were not significantly increased at 18 h after the procedure. No significant changes in ejection fractions, 12-lead ECGs, and regional wall motion occurred in any of the patients studied. In conclusion, PBMV causes modest early elevation of CPK-MB. This elevation is not associated with changes in LV systolic function and does not interfere with the diagnosis of acute myocardial infarction using the enzyme elevation criteria.

Significant changes in the distribution of histologic types of lung cancer in Hong Kong.

A retrospective study of 2385 Chinese patients with proven carcinoma of lung was performed. The autopsy incidence was 3.3%. Most patients presented in the seventh decade. The age distribution was 24-94 yrs with a mean age of 63 yrs. The four major histologic types (37.3% of adenocarcinoma, 33.4% of squamous cell carcinoma, 13.7% of small cell carcinoma and 14.7% of large cell carcinoma) accounted for 99.1% of the cases. Among the four, adenocarcinoma was the most common histologic type, particularly for females and there has been an increase in the incidence of adenocarcinoma in recent years. This trend has been observed and reported in many affluent countries. In Hong Kong, the frequency of adenocarcinoma among Chinese females is exceptionally high.

Incidence of ras oncogene activation in lung carcinomas in Hong Kong.

BACKGROUND: In Hong Kong, lung carcinomas contribute to the majority of cancer deaths among Chinese. Point mutational activation of ras oncogenes has been observed in several populations. The incidence of these mutations in Hong Kong lung carcinomas was investigated. METHODS: Lung resections obtained from 52 Chinese patients whose conditions were newly diagnosed as non-small cell lung cancer, paraffin sections from 29 Chinese patients with previously diagnosed adenocarcinoma of the lung, and paraffin sections from 49 squamous cell carcinomas were examined for the presence of point mutations in Ki-ras codon 12, N-ras codon 61, and Ha-ras codon 12 oncogenes by allele-specific hybridization after specific amplification of appropriate regions of the DNA using the polymerase chain reaction. RESULTS: Among the 130 lung carcinomas investigated, Ki-ras point mutations were detected in seven cases, of which six were adenocarcinomas and one a squamous cell carcinoma. No mutations were detected in the N-ras and Ha-ras codons. CONCLUSIONS: The incidence of Ki-ras codon 12 point mutational activation in Chinese patients with adenocarcinomas was 6 of 63 (9.5%). The incidence of Ki-ras 12 point mutational activation among men with lung adenocarcinomas in Hong Kong (6 of 32 patients, 18.8%) is significantly different from that in women in Hong Kong (0 of 31 patients, 0%). Although ras oncogenes are implicated as having a role in the development of lung adenocarcinomas, especially among smokers, it is clear from these data that they are not associated with the unusually high incidence of lung adenocarcinomas among women in Hong Kong.

Antineutrophil cytoplasmic antibody and gallium lung scintiscan in usual interstitial pneumonitis.

A 2 year old Chinese boy was reported in whom there was an association between usual interstitial pneumonitis (UIP) and serum antineutrophil cytoplasmic antibody of the classical cytoplasmic type (cANCA). The concentration of cANCA reflected disease activity and decreased during a 6-week course of prednisolone. The gallium lung scintiscan index correlated with his disease activity. Both the serum cANCA concentration and the gallium lung scan could be used to monitor responses to treatment in this patient with UIP.