Prognostic factors associated with clear cell sarcoma in 14 Chinese patients.

PURPOSE. To identify prognostic factors associated with clear cell sarcomas in 14 Chinese patients. METHODS. Medical records of 7 men and 7 women (mean age, 36 years) with histologically confirmed clear cell sarcoma of tendons and aponeuroses were reviewed. Patient demographics, tumour characteristics, and treatment modalities were retrieved. Prognostic factors associated with favourable 5-year survival were determined. RESULTS. The most affected sites were the thigh (n=5) and the foot (n=4); the mean time from symptom onset to diagnosis was 9.5 months. The tumour stage at diagnosis was IIA in 8 patients, IIB in 2, and III in 4. The mean tumour size was 4.5 cm in diameter. One patient was lost to follow-up. For the remaining 13 patients, the mean time to disease-related mortality was 2.5 years. Nine patients had distant metastases; the most common sites were lungs and pleura (n=7), followed by distant lymph nodes (n=4), bone (n=2), pericardium (n=2), and brain (n=1). All patients underwent surgical excision. Three women and one man (mean age, 27 years) attained 5-year disease-free survival. All had stage IIA tumours at diagnosis. Their mean tumour size was 1.75 cm in diameter, which was significantly smaller than that of all patients (4.5 cm). Tumour size of ≤ 2.5 cm in diameter (p=0.004) and stage IIA tumour at diagnosis (p=0.04) were significant prognostic factors for 5-year survival. CONCLUSION. Tumour size of ≤ 2.5 cm and early stage tumour are associated with 5-year disease-free survival. Early detection is crucial for the prognosis of clear cell sarcomas.

Minimally invasive technology in the management of breast disease.

Minimally invasive surgery is gaining popularity around the world because it achieves the same or even superior results when compared to standard surgery but with less morbidity. Minimally invasive breast surgery is a broad concept encompassing new developments in the field of breast surgery that work on this minimally invasive principle. In this regard, breast-conserving surgery and sentinel lymph node biopsy are good illustrations of this concept. There are three major areas of progress in the minimally invasive management of breast disease. First, percutaneous excisional devices are now available that can replace the surgical excision of breast mass lesions. Second, various ablative treatments are capable of destroying breast cancers in situ instead of surgical excision. Third, mammary ductoscopy provides a new approach to the investigation of mammary duct pathology. Clinical experience and potential applications of these new technologies are reviewed.

Case of fibromatosis of male breast.

Extra-abdominal fibromatosis of the breast is rare with the clinical and radiological features closely resembled malignant breast tumour. We describe, in a 40-year-old Chinese male patient with a palpable left breast mass, the clinical, radiological and pathological features of this benign though locally aggressive tumour.

Opportunistic breast cancer screening in Hong Kong; a revisit of the Kwong Wah Hospital experience.

OBJECTIVE: To analyse the performance of opportunistic breast screening in local Well Women Clinics during the 5-year period from 1998 to 2002, with reference to international as well as our own earlier experience (1991 to 1993 to 1995). DESIGN: Prospective study. SETTING: Well Women Clinics in regional Hong Kong hospitals. PARTICIPANTS: Women attending the Well Women Clinics of the Tung Wah Group of Hospitals for breast cancer screening. MAIN OUTCOME MEASURES: All screening-detected breast cancers. RESULTS: After 46 637 screening mammograms and excluding palpable masses detected by the patients themselves, 232 women were detected with cancers, yielding a crude detection rate of 5.0 per 1000. Age range for cancer detection was 35 to 72 (median, 49) years. Clinic staff detected palpable lumps in 83 patients, constituting 36% of the detected cancers, of which 15 (6.5% of all detected cancers) were not identified by mammography. The cancer detection rate was 5.9 per 1000 in the age-group 40-49 years and 3.7 per 1000 in those 50 years or older. The cancer detection rate was 58.5 per 1000 in the high-risk group (aged <40 years with positive family history). The minimal cancer detection rate was 2.2 per 1000, representing 45% of all cancers whose pathology was available to us. Ductal carcinoma in situ comprised 28% of all such cancers. Our recall rates were 4.6% for additional views only, 3.3% for ultrasound only, and 2.3% for both. Positive predictive values for abnormal mammograms and biopsies were 4.9% and 26.0%, respectively. CONCLUSION: Mammographic screening has been reported to reduce mortality up to 35% in western countries. However, data concerning Asian Chinese populations are meagre. Our Well Women Clinics pioneered large-scale self-referred breast screening in Hong Kong. Despite the lower incidence of breast cancers than in Occidental populations, our screening programme performed comparably to those in the West, and has improved over time. Our screening service for self-referred women detected breast cancers even at an early stage, which facilitated a better prognosis and more treatment options, whilst appearing to be highly acceptable to our community. Besides, it could provide training and expertise in breast radiology and mammography, which are essential prerequisites for establishing population screening.

Randomized clinical trial comparing blue dye with combined dye and isotope for sentinel lymph node biopsy in breast cancer.

BACKGROUND: Use of blue dye alone as a marker for sentinel lymph node (SLN) biopsy is effective, but combining it with isotope marking can improve the success rate. Use of the isotope adds extra cost and there are potential radiation hazards. The two techniques were compared in a randomized trial. METHODS: Women with early breast cancer (less than 3 cm) and no palpable axillary nodes were recruited. Women older than 70 years with multicentric cancers or previous surgery to the breast or axilla were excluded. Patients were randomized to either blue dye alone or combined mapping for SLN biopsy. All women had a level I and II axillary dissection after the SLN biopsy. RESULTS: A total of 123 patients were recruited, of whom five were excluded from analysis. Blue dye alone was used in 57 women and 61 had combined mapping. Baseline demographic data were similar in the two cohorts. The success rate of SLN biopsy was higher with combined mapping than with blue dye alone (100 versus 86 per cent; P = 0.002). The accuracy and false-negative rate were similar (accuracy 100 per cent for combined mapping versus 98 per cent for blue dye; false-negative rate 0 versus 5 per cent). CONCLUSION: Combined mapping was superior to blue dye alone in identification of the SLN, but accuracy and false-negative rates were similar.

Imaging of gastrointestinal stromal tumour (GIST).

Gastrointestinal stromal tumour (GIST) represents the most common kind of mesenchymal tumour that arises from the alimentary tract. GIST is currently defined as a gastrointestinal tract mesenchymal tumour containing spindle cells (or less commonly epithelioid cells or rarely both) and showing CD117 (c-kit protein) positivity. Targeted molecular therapy of non-resectable GIST using imatinib, a specific tyrosine kinase receptor inhibitor, represents a real milestone in the management of solid malignancy. Imaging studies, both anatomical and functional, are playing an increasingly important role in management of patients with GIST. This review illustrates the radiological appearance of GISTs and the site-specific roles of each imaging tool. Clinical features and radiological differential diagnosis of GIST are also discussed.

Anatomical justification of Belghiti's 'liver hanging manoeuvre' in right hepatectomy with anterior approach.

BACKGROUND: In cases of right hepatectomy for huge tumour encroaching onto the diaphragm, the 'anterior approach' is the most common surgical procedure undertaken. The 'liver hanging manoeuvre' has been described previously as an adjunct to this procedure. It involves the dissection of a retrohepatic avascular plane anterior to the surface of the inferior vena cava. A tape is then passed through and the liver is resected under suspension. METHODS: Cadaveric specimens were used to identify the structural relationship of the avascular plane and also to determine whether it is truly avascular. RESULTS: Thirteen cases were analysed. The mean length of the avascular tunnel was 6.4 +/- 1.0 cm. The median number of accessory hepatic veins within the tunnel was two (zero to three). At the caudal half of the tunnel, the median number of veins was two (zero to three). As for the cranial half of the tunnel, there were two cases with one vein in each. CONCLUSIONS: The key to the liver hanging manoeuvre is to develop the retrohepatic tunnel. However, our study showed that it is not absolutely avascular. During the blind dissection, there is a chance of damaging a retrohepatic vein. This may result in troublesome haemorrhage within the confines of the tunnel. Video-assisted dissection of this region may help in visualisation, and hence control, in order to avoid bleeding.

First fatal case of enterovirus 71 infection in Hong Kong.

Enteroviruses are a common cause of childhood infections, from hand, foot and mouth disease, to lethal brainstem encephalitis. Enterovirus 71 was first isolated in 1969. Brainstem encephalomyelitis and pulmonary oedema are postulated to be causally related and have been found to be a common feature of fatal enterovirus 71 cases. A fatal case of enterovirus 71 infection in a 2-year-old, previously healthy boy is reported. He presented to the Department of Paediatrics with clinical features of sepsis within 3 days of onset of fever. A few minutes after injection of midazolam, fentanyl and vecuronium for intubation, cardiac arrest developed and was not amenable to various treatment modalities. Pulmonary haemorrhage and oedema were noted during intubation, and postmortem examination confirmed the presence of brainstem encephalomyelitis.

Spontaneous intramural hematoma of stomach.

BACKGROUND: Intramural hematoma occurs uncommonly in the gastrointestinal tract and very rarely in the stomach. In case of a spontaneous gastric hematoma, the few previously reported patients all had certain predisposing factors. However, truly spontaneous intramural hematoma of the stomach without an identifiable cause has not been reported before. METHOD: Emergency total gastrectomy was performed in a 49-year-old man with such pathology and the diagnosis was made postoperatively. RESULTS: The patient required further laparotomy on day 10 for drainage and debridement of a subphrenic abscess. He recovered uneventfully from the second operation. After an extensive pathological search, no predisposing factors could be found. The patient remains in good health 18 months after the operations. CONCLUSION: Spontaneous intramural gastric hematoma is extremely rare. But even rarer is when predisposing conditions or lesions are absent.

Neonatal Marfan syndrome: a case report.

A case of neonatal Marfan syndrome is presented. The patient was noted to have cardiomegaly and tricuspid regurgitation on antenatal ultrasound scan. She was born with long, slender fingers and toes, an aged appearance and non-paralytic hypotonia. Echocardiogram revealed a dilated right atrium, right ventricle, dysplastic tricuspid valve and severe tricuspid regurgitation. She subsequently died of severe heart failure. Post-mortem examination showed the pathological features of lobar emphysema and cystic medial necrosis of the aorta. These features supported the diagnosis of neonatal Marfan syndrome. Nucleotide sequencing showed substitution of G by A at codon 1032 in exon 25 located in the long arm of chromosome 15. This resulted in the substitution of a cysteine by a tyrosine. A de novo mutation is suggested by the absence of affected family members.

Case report: two cases of biliary papillomatosis with unusual associations.

Papillomatosis arising from the biliary tree is a well recognized but rare entity. We encountered two patients with this condition. However, one of them had associated hepatocellular carcinoma and cirrhosis and the other had concomitant recurrent pyogenic cholangitis. To our knowledge, these associations have not been reported before. We, therefore, present these clinical problems and highlight the added difficulty in the management of these patients.

Gastric polypoid lesions--illustrative cases and literature review.

Currently, upper gastrointestinal endoscopies are frequently performed for patients with various gastrointestinal symptoms. From time to time, lumps and bumps in the stomach are encountered on endoscopy. Four cases of gastric polypoid lesions are presented. The classification, differentiation, and management approach to these lesions are discussed. Although there is consensus that all gastric adenomatous polyps should be removed, as should gastric hyperplastic polyps that are symptomatic and/or bear dysplastic foci on forceps biopsy, controversy still exists over the management of asymptomatic gastric hyperplastic polyps that do not bear any dysplastic focus on forceps biopsies. Endoscopic ultrasonography (EUS) has a promising role in the evaluation of gastric submucosal polypoid lesions.

Mucosal lymphangiectasia in gastric adenocarcinoma.

OBJECTIVE: To describe the occurrence and significance of mucosal lymphangiectasia in gastric adenocarcinoma. DESIGN: One hundred consecutive gastrectomies for adenocarcinoma were reviewed, using 25 consecutive gastroscopically biopsied gastrectomy specimens with peptic ulcers as negative controls. SETTING: The specimens were collected over a period of 25 months in two general hospitals and processed according to a standard protocol. PATIENTS: Chinese living in Hong Kong. RESULTS: Twenty cases of adenocarcinoma were found to show mucosal lymphangiectasia, which was arbitrarily defined as the presence of ectatic lymphatic channels in the lamina propria having maximum dimensions greater than that of a foveolar gland. The ectatic lymphatics were lined by simple endothelium, devoid of fibromuscular wall, and they either were optically empty or contained scant mononuclear leukocytes. None of the patients had preoperative evidence of malabsorption syndrome or protein-losing enteropathy. Lymphangiectasia was most readily seen in the superficial lamina propria near the main tumor. In 10 cases (50%), lymphangiectasia extended to the nonneoplastic part of the gastric mucosa, at a distance of at least 2 cm away from the main tumor. Tumor emboli were seen in the ectatic lymphatics in 11 cases (55%). In two cases (10%), the distal line of resection was involved by intramucosal lymphatic spread. The tumor permeating the lymphatics did not evoke any inflammatory or desmoplastic reaction in the perilymphatic lamina propria, similar to the phenomenon of so-called lymphangitis carcinomatosa. In eight cases (40%), there were foci beyond the main tumor where mucosal lymphangiectasia was present, but without tumor in its immediate vicinity. All (100%) of the 20 stomachs with mucosal lymphangiectasia had metastases in regional lymph nodes, whereas only 59 of the 80 cases (73.75%) without lymphangiectasia were node-positive (P < .025). All node-negative cases did not show lymphangiectasia. Twenty-five consecutive gastrectomies for peptic ulcer disease that had undergone preoperative mucosal biopsies showed no lymphangiectasia, suggesting that mucosal biopsy was not the cause of mucosal lymphangiectasia. CONCLUSIONS: (1) Gastric mucosal lymphangiectasia is associated with carcinoma but not peptic ulcer, (2) Mucosal lymphangiectasia in gastric carcinoma signifies lymph node metastases, and (3) Gastric carcinoma can spread along the mucosa via intramucosal lymphatics.

Examination of mammalian basic helix-loop-helix transcription factors using a yeast one-hybrid system.

Basic helix-loop-helix (bHLH) transcription factors play diverse roles in controlling many developmental events. Although a great deal is understood about how bHLH factors activate gene transcription via E-box DNA consensus sequences, studies of bHLH factor function in higher eukaryotes often have been hindered by the presence of multiple family members. As a first step in developing a simplified in vivo system to examine bHLH factor activities, we examined whether the bHLH muscle regulatory factors MRF4 and MyoD function appropriately in yeast. We show that Gal4-MRF4 fusion proteins, or native MRF4 proteins, activate expression of an E-box HIS3 reporter gene whereas MyoD proteins remain inactive. Deletion of the MRF4 transcription activation domain (TAD) or point mutations that abolish MRF4 DNA interactions inhibit HIS3 expression. Substitution of the MRF4 TAD with the Gal4 TAD also produces a functional protein, demonstrating that these transcription activation domains are functionally equivalent in yeast. Replacement of the MRF4 TAD with the related MyoD TAD, however, generates an inactive protein, suggesting that some specificity exists between bHLH family members. Using this experimental system, we also demonstrate that mammalian cDNA libraries can be screened successfully for cDNAs encoding novel bHLH proteins that interact with E-box targets. Thus, this in vivo yeast system provides a novel approach to facilitate functional studies of bHLH factor regulation.

Heterogeneity of human blood monocyte: two subpopulations with different sizes, phenotypes and functions.

Human blood mononuclear cells from normal adults were collected after density-cut centrifugation and monocytes were then isolated by removal of lymphocytes using the techniques of E-rosetting and cell adhesion. The purified monocytes were further analysed by velocity sedimentation, and two distinct subpopulations with different cell sizes were obtained. The larger monocytes were 17.0 +/- 1.8 microns in diameter with a mean sedimentation rate (SR) of 7.0 +/- 0.6 mm/hr, while the smaller monocytes were 9.5 +/- 0.8 microns in size and 4.1 +/- 0.2 mm/hr in SR. The population ratio of larger:smaller cells was approximately 2:1 (66 +/- 2.8%:34 +/- 1.6%). Both cell populations exhibited a high positive rate (> 98%) in both the non-specific esterase and the peroxidase stain. However, the larger cells had much higher phagocytic activity than the smaller ones. Furthermore, the expression of monocyte-associated antigens was also different between these two subpopulations. Thus, while most of the larger monocytes (98%) could be recognized by monoclonal antibodies MY7 and OKM1, only some (35 and 61%, respectively) of the smaller monocytes could react with those antibodies. In addition, the larger monocytes secreted a significant amount of monokines including interleukin-1 beta (IL-1 beta), tumour necrosis factor-alpha (TNF-alpha) and prostaglandin E2 (PGE2) and their production increased in proportion to the level of stimulation by bacterial lipopolysaccharide (LPS), whereas the production of monokines by the smaller monocytes remained at low levels and did not respond to LPS stimulation. These results reveal the existence of phenotypic and functional heterogeneity in human blood monocytes.

The MRF4 activation domain is required to induce muscle-specific gene expression.

MRF4 is a member of the basic helix-loop-helix muscle regulatory factor family that also includes MyoD, myogenin, and Myf-5. Overexpression of MRF4 or the other muscle regulatory factors in fibroblasts converts the cells to differentiated muscle fibers and transcriptionally activates expression of endogenous and cotransfected muscle genes. Although these factors induce a similar phenotype, they also exhibit some distinct biological activities. For example, MyoD trans activates alpha-actin and troponin I reporter genes to very high levels, whereas MRF4 efficiently activates only alpha-actin expression. Since these proteins have a common basic helix-loop-helix domain, it is likely that portions of the proteins outside of this region impart some specificity to the activity of each muscle regulatory factor. As an initial step in determining the mechanism by which MRF4 and MyoD activate gene transcription, the transcriptional activation domain of MRF4 has been characterized. Experiments utilizing chimeric proteins containing the yeast GAL4 DNA-binding domain and portions of the MRF4 protein indicate that the MRF4 activation domain is located within amino acids 10 to 30. This amino terminus is both necessary and sufficient to elicit a transcriptional response in transfected cells. The MRF4 activation domain and the related amino-terminal MyoD activation domain are capable of substituting for one another in converting fibroblasts to a myogenic phenotype and in activating expression of an alpha-actin reporter gene, although the MRF4 and MyoD activation domains on these chimeric proteins also dictate the specificity of transcriptional activation. The different primary amino acid sequences of these regions leave open the possibility that different coregulator proteins interact with the muscle regulatory factors to elicit their correct transcriptional activity during skeletal muscle development.

Congenital juvenile granulosa cell tumour of the testis: report of a case showing extensive degenerative changes.

Juvenile granulosa cell tumour is a rare neoplasm of the testis which occurs predominantly in infancy and which may be associated with sex chromosomal abnormalities. We report an unusual case with deceptive histological features resulting from extensive degenerative changes. In the pedunculated intra-abdominal mass resected from a 1-month-old male baby with 45,X/46,X,iso(Yq) mosaicism, there were multiple large cystic spaces devoid of cellular lining or lined by flat nondescript cells, mimicking various cystic lesions such as multicystic mesothelioma, cystic lymphangioma and cystic dysplasia. The cysts were separated by a highly vascularized fibrous stroma. Only in very rare cysts and the smaller cysts in the region of the pedicle were granulosa cells identified, permitting a diagnosis of juvenile granulosa cell tumour to be made.

Dual function of monocytes on the regulation of granulopoiesis.

The intrinsic balance of monocyte-derived mediators in the regulation of granulopoiesis was studied. Both the granulocyte macrophage colony-stimulating factors (GM-CSFs) and the colony inhibitory factor (prostaglandin E2; PGE2), were found to be elaborated by cultured monocytes, and most of these mediators were secreted during the first 4 days after monocyte cultivation. The concentration of monocytes in culture had a direct effect on the amount of mediator production. A maximum amount of mediators was noted to range from 2 x 10(5)-2 x 10(6) monocytes per 35 mm Petri dish. It was also found that the monocytes responded to the exogenous stimulus (lipopolysaccharide, LPS) in a biphasic manner. The optimal concentration of LPS in stimulating production of the tested mediators was 3.2 micrograms/ml. At higher concentrations (greater than 3.2 micrograms/ml), both the release of GM-CSFs and PGE2 were suppressed. The addition of indomethacin to the culture system resulted in a confirmatory increase in GM-CSFs production at LPS concentration higher than 3.2 micrograms/ml. The response of monocytes to endogenous regulators (GM-CSFs and PGE2) was also determined. The addition of GM-CSFs to the cultures promoted PGE2 production by monocytes in dose-dependent with an optimal concentration of around 450 units/ml. Alternatively, treatment of monocytes with PGE2 (10(-9) to 10(-10) M) also enhanced, to a certain extent, the production of GM-CSFs. The coincidence of the peaks of GM-CSFs and PGE2 release demonstrated in vitro suggested the existence of an intrinsic balance mechanism in the regulation of granulopoiesis by monocytes.

Sinus histiocytosis with massive lymphadenopathy, a report of 2 cases in Chinese.

Two Chinese patients with sinus histiocytosis and massive lymphadenopathy are reported. The results of enzyme and immunohistochemical studies are presented.