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Biomedical subjects

L K Tan

Publications and source records attributed to L K Tan.

At least 55 records · Page 3Linked to original sources

Expression of TERT in early premalignant lesions and a subset of cells in normal tissues.

Activation of telomerase, the enzyme that synthesizes the telomere ends of linear chromosomes, has been implicated in human cell immortalization and cancer cell pathogenesis. Enzyme activity is undetectable in most normal cells and tissues, but present in immortal cells and cancer tissues. While expression of TERC, the RNA component of telomerase, is widespread, the restricted expression pattern of TERT, the telomerase catalytic subunit gene, is correlated with telomerase activity, and its ectopic expression in telomerase-negative cells is sufficient to reconstitute telomerase activity and extend cellular lifespan. We have used in situ hybridization to study TERT expression at the single-cell level in normal tissues and in various stages of tumour progression. In normal tissues, including some that are known to be telomerase-negative, TERT mRNA was present in specific subsets of cells thought to have long-term proliferative capacity. This included mitotically inactive breast lobular epithelium in addition to some actively regenerating cells such as the stratum basale of the skin. TERT expression appeared early during tumorigenesis in vivo, beginning with early pre-invasive changes in human breast and colon tissues and increasing gradually during progression, both in the amount of TERT mRNA present within individual cells and in the number of expressing cells within a neoplastic lesion. The physiological expression of TERT within normal epithelial cells that retain proliferative potential and its presence at the earliest stages of tumorigenesis have implications for the regulation of telomerase expression and for the identification of cells that may be targets for malignant transformation.

Breast Neoplasms↗

Outcome of early cervical carcinoma treated by Wertheim hysterectomy with selective postoperative radiotherapy.

Seventy-five consecutive patients with histologically confirmed FIGO stage IB-IIA cervical carcinoma who underwent Wertheim hysterectomy were studied retrospectively. Poor prognostic factors were found in 42 (56%) patients in whom postoperative adjuvant pelvic irradiation was given. The overall disease-free survival rate was 78% at 5 years and 75% at 9 years. The tumour recurrence rate was 12.1% in the low-risk patients and 35.7% in the high-risk patients. Tumour recurrences occurred significantly more frequently in patients with tumours with high grade squamous cell carcinomas and adenosquamous carcinoma. No recurrences occurred in patients with adenocarcinomas. After adjuvant radiotherapy, there was no statistically significant difference in the recurrence rates between lymph node positive and negative patients (26.7% and 19.6% respectively), however extrapelvic recurrences were more common in those with diseased lymph nodes. The recurrence rate was 40% in patients with involved resection margins compared to 16.7% of patients with clear margins. The recurrence rates were similar for patients with and without tumour embolisation of vascular/lymphatic channels. Wertheim hysterectomy with postoperative pelvic irradiation for selected high-risk patients was an effective treatment for FIGO stage IB-IIA cervical carcinoma. Despite radiotherapy, the high-risk patients still experienced a high tumour recurrence rate.

Adenocarcinoma↗

p53 over-expression in laryngeal carcinoma is not predictive of response to radiotherapy.

It has been suggested that alteration involving the p53 gene may influence tumour response to radiotherapy. If this were so, then p53 overexpression (which is usually associated with p53 mutation and readily detectable in routine diagnostic pathology) may help determine the most appropriate form of cancer therapy. p53 expression was assessed in 90 formalin-fixed paraffin-embedded laryngeal carcinomas that were subsequently treated with radiotherapy. The polyclonal antibody DO1 (1 in 50 dilution) was used, together with an avidin-biotin immunoperoxidase technique, but in the absence of any additional antigen retrieval techniques. p53 expression was assessed and correlated with various clinicopathological parameters. Using Chi square analysis, no significant difference between p53 positive and p53 negative lesions was found for response to radiotherapy, as measured by survival and recurrence rates. Furthermore, no correlation with p53 expression was found for tumour size, nodal metastasis, sex, age, alcohol intake, tobacco habit and histological grade. This absence of correlation may in part be explained by discrepancies between immunohistochemical detection of p53 and p53 mutation, although the lack of predictive response to radiotherapy mimics that recently found for irradiated head and neck cancer cell lines.

Adult↗

Comparison of direct monocular endoscopic, two- and three-dimensional display systems on surgical task performance in functional endoscopic sinus surgery.

Surgeons performing functional endoscopic sinus surgery (FESS) traditionally rely on direct endoscopic viewing through a single monocular Hopkins rod lens telescope. While the majority of surgeons have found this satisfactory, most other endoscopic surgical specialties have moved to 2-D video endoscopy, where a monoscopic image is presented on a television monitor. This study set out to determine whether 2-D or 3-D display systems had any advantage over direct endoscopy in FESS. Ten otolaryngology trainees performed a series of standardized procedures on a FESS model using direct endoscopic vision, 2-D and 3-D. A performance score was obtained by dividing the execution time by the number of tasks achieved. There was a significant difference in both surgical and diagnostic task performance with 2-D (mean scores 56.8 and 41.1) performing better than direct endoscopy (mean scores 94.1 and 74.1) (P < 0.05). Tasks were also performed significantly better with 3-D compared with 2-D (P < 0.05).

Endoscopy↗

Nasal mucociliary clearance and salmeterol.

In vitro studies have suggested that beta 2-adrenergic agents increase the ciliary beat frequency in human respiratory epithelium. We carried out a randomized, double-blind placebo-controlled trial to investigate the effects of a topical spray, salmeterol, on nasal mucociliary clearance using the saccharin test. Thirty-three healthy adults were recruited. There was a 21% reduction of nasal mucociliary transport time of saccharin with salmeterol compared to placebo (P = 0.0001). There was no effect of age, sex, order of treatment, interval between spray and saccharin test, or history of seasonal allergic rhinitis on the improvement in clearance times.

Administration, Topical↗

Stage IA uterine serous carcinoma: a study of 13 cases.

Although in endometrioid type endometrial carcinoma depth of invasion is a powerful predictor of extrauterine disease and survival, in serous carcinoma its importance is unclear. Recurrences and death in patients with serous tumors confined to the endometrium or an endometrial polyp have been reported. In other studies, however, the absence of myometrial invasion was correlated with a more favorable course. In an attempt to clarify this issue, we reviewed 13 completely staged, stage IA serous carcinomas with follow-up from 10 to 93 months (median 38), in which extensive histologic examination had been performed. Serous carcinoma was identified in an endometrial polyp in six cases, in an endometrial polyp and associated endometrium in four, and solely in the endometrium in three cases. No other histologic types of endometrial carcinoma were present, and there was no myometrial invasion. Multifocal serous intraepithelial carcinoma was also seen in 12 cases. Two of the patients died of disease with intraabdominal carcinomatosis at 10 and 14 months after presentation. The overall estimated survival was 83%, showing a relatively favorable prognosis. In conclusion, although the absence of histologically detected myometrial invasion may be associated with recurrences and death in serous carcinoma, an accurately assessed stage based on a careful histologic examination appears to be, at present, the most reliable predictor of survival.

Aged↗

Surgical bone wax causing epistaxis.

A case of recurrent epistaxis caused by bone wax in the nasal cavity is reported. This is the first reported case of a nasal complication due to surgical bone wax.

Aged↗

Antigen retrieval: p53 staining in benign, pre-malignant and malignant tissues of the larynx.

Antigen retrieval techniques have been reported to increase p53 detection. Using an antigen retrieval technique applied to immunohistochemistry, a study was performed on 67 laryngeal lesions (21 benign, 16 carcinoma in situ, 30 squamous cell carcinoma). p53 staining was observed in 30% of carcinoma in situ specimens and 53% of squamous cell carcinomas but was not detected prior to antigen retrieval in any benign lesion. However, over-expression of p53 was identified in 92.5% of benign lesions after antigen retrieval using the microwave oven heating. There was also increased p53 staining in both the carcinoma in situ (43.7%) and squamous cell carcinomas (30.0%) after antigen retrieval. We conclude that antigen retrieval using microwave oven heating increases immunohistochemical detection of p53 such that positive staining is observed in benign conditions. We postulate that this apparent over-expression is a manifestation of the wild-type protein, which may be found in more evidence in basal cells than suprabasal cells. Our results thus offer a cautionary note to such studies involving squamous cell cancers that attempt to correlate p53 over-expression with clinical parameters.

Antigens, Neoplasm↗

Spiculated axillary adenopathy.

PURPOSE: To describe the mammographic and sonographic appearance of a pattern of spiculation of the contour of axillary lymph nodes. MATERIALS AND METHODS: Eleven cases of axillary nodes with spiculated contour were prospectively identified on routine mammograms. All cases were in women with breast cancer. Sonograms of axillary nodes were available in three cases. Medical records were reviewed, and histologic and nodal histopathologic findings and patient outcome were correlated. RESULTS: All women had primary, invasive breast carcinoma. Although disease was evident mammographically, four of nine women for whom the results of the physical examination were known did not have palpable adenopathy. Nodes were iso-to hyperdense (compared with breast parenchyma) on mammograms and were hypoechoic with irregular margins on sonograms. The spiculated pattern of the nodes correlated with extension of metastatic tumor in axillary nodes into perinodal fat. At a mean follow-up of 17 months, one patient was dead of disease, eight were alive with disease, and two were alive without disease. CONCLUSION: A pattern of spiculated axillary adenopathy in a patient with breast cancer appears to be consistent with extranodal extension of tumor into perinodal fat. This finding suggests a biologically aggressive tumor with a poor prognosis.

Adult↗

Age-related prognostic factor analysis in non-Hodgkin's lymphoma.

BACKGROUND: Age is known to have an important influence on survival in non-Hodgkin's lymphoma (NHL). This observation and the relationship of age to other prognostic factors are of interest in designing treatment programs for these patients. This study was conducted to investigate the relationship of age to other known prognostic variables and survival in NHL. PATIENTS AND METHODS: Data on clinical features, treatment, response, survival and cause of death from 547 patients with NHL diagnosed between 1980 and 1989 were collected and analyzed by age group. Multivariate analysis of prognostic factors and a survival comparison to an age and sex matched control population were performed. RESULTS: Survival curves for 5-year age groups up to and including age 60-64 years were similar, after which a major effect of age upon survival was apparent. When groups aged < 65 years and > and = 65 years were compared, there were similar proportions of most known prognostic factors, except for a higher proportion with increased lactate dehydrogenase (LDH) levels and extranodal disease in older patients. When analyzed by age group, older patients had a lower response rate to initial therapy and salvage treatments. In younger patients, several recognized prognostic variables were found to lack significance. CONCLUSIONS: Prognostic variables differ between younger and older patients with NHL. Age, histology, LDH elevation and gender are less important in younger patients; only bulky disease is more important than in older patients. A lower response rate, poor response to salvage therapy and excess mortality, often due to concurrent diseases, were apparent in older patients. Age is a significant prognostic factor only in patients age > and = 65 years.

Age Factors↗

Nasal complications of the direct transnasal approach to the pituitary fossa.

The transnasal trans-sphenoidal approach to the pituitary fossa is direct and fast. This study is aimed at establishing the nasal morbidity arising from this approach. One of the 25 patients developed secondary haemorrhage and another suffered recurrent minor epistaxis. The peak nasal inspiratory flow rates showed no significant difference between the left and right anterior nasal passages. Adhesions were noted in seven patients and no septal perforations were found. Three patients, who had no previous nasal symptoms, developed postoperative unilateral nasal obstruction, two secondary to left septal deviation and the other caused by right-sided anterior nasal space adhesions. The study suggests that the operation has a low nasal morbidity.

Adenoma↗

Glycerol versus radiofrequency rhizotomy--a comparison of their efficacy in the treatment of trigeminal neuralgia.

Ever since the anatomical basis of trigeminal neuralgia has been postulated to be vascular compression, microvascular decompression has been gaining acceptance as the definitive treatment of the condition. However, the majority of patients are over 50 years of age, and posterior fossa procedures carry significant risk in terms of morbidity and mortality. Radiofrequency and glycerol rhizotomy are the two procedures commonly performed in patients considered unsuitable for posterior fossa craniectomy. This study attempts to assess the relative merits and demerits of these two procedures and seeks to establish indications for each. It is felt that glycerol rhizotomy is better as the first line treatment.

Adult↗

Imaging patterns in melioidosis.

Melioidosis is an infectious disease caused by Pseudomonas pseudomallei. It is seldom diagnosed promptly and, if untreated, can lead to an 80-100% mortality rate. Twenty-eight patients with melioidosis were identified over a 6 year period, and their imaging patterns were analysed. Respiratory infections were the commonest form of presentation, frequently shown as diffuse airspace consolidation, and accounted for the highest mortality. Visceral and musculoskeletal infections were associated with chronicity and a high relapse rate. Multifocal splenic abscesses were a common occurrence. Septic arthritis of the knee was frequently seen. The majority of patients had diabetes mellitus and chronic ill-health. An increased awareness of the disease can contribute to its early detection and appropriate treatment.

Abscess↗

Non-Hodgkin's lymphoma in Saskatchewan. A review of 10 years' experience.

BACKGROUND: The incidence and treatment of non-Hodgkin's lymphoma (NHL) have changed in recent years. This study was intended to compare current features with a previous study (1966-1975) and assess the impact of these changes in our jurisdiction. METHODS: Clinical features and treatment of 547 patients with NHL registered at our center from January 1980 through December 1989 were reviewed, including reassessment of histologic type in each patient. Multivariate analysis of potential pretreatment prognostic factors was performed using the Cox proportional hazards model, and survival was analyzed in relation to treatment outcome. RESULTS: This review includes virtually all incident cases of NHL in a defined geographic area, representing an average annual incidence of 11.3/100,000 population. The male-to-female ratio was 1.1:1, median age was 65 years (range, 4-92 years). Median survival time (MST) of 482 patients with disease diagnosed antemortem was 4.8 years (95% confidence interval [CI], 3.7-6.1 years), 52% of whom have died. Thirty-nine percent of patients with disease classified by the International Working Formulation (IWF) had low-grade disease (MST, 103 months); 27% had intermediate disease (MST, 62 months), and 30% had high-grade disease (MST, 35 months). Sixteen percent of patients had associated neoplasms: 4 acute leukemias, 35 skin cancers, and 37 miscellaneous solid tumors. Results of radiation therapy (RT), chemotherapy (CT), and combined CT/RT were analyzed. Survival correlated strongly with responsiveness to treatment. Considering all patients treated with CT, anthracycline-containing CT was associated with the highest response rate, and survival time (more than 48 months) may have been affected by the addition of this agent. A survival advantage for patients with bulky Stage I and II disease treated with consolidative RT after CT is suggested, but not for more advanced stage disease. The proportional hazards model identified histologic type, disease stage, patient age, hemoglobin level, lactate dehydrogenase (LDH) level, bulky abdominal disease, and systemic "B" symptoms as significant independent prognostic factors influencing survival. CONCLUSIONS: The incidence of NHL has increased, and the survival of patients with high-grade disease has improved significantly since the previous study. A high incidence of other associated malignancies was demonstrated in this group of patients with NHL. Recognition of prognostic factors should permit a rational application of innovative treatments for patients in unfavorable prognostic categories.

Adolescent↗

Ovarian serous borderline tumors with lymph node involvement. Clinicopathologic and DNA content study of seven cases and review of the literature.

Although several studies have established the excellent prognosis of ovarian serous borderline tumors (OSBTs) in general, the significance of lymph node involvement has not been thoroughly addressed. In this article, we describe seven OSBTs with lymph node involvement and their DNA content and S-phase fraction. Lymph node involvement was identified at presentation in four cases (pelvic, paraaortic, and omental) and after 4, 5, and 7 years in the other three (omental, scalene, and cervical, respectively). In the first group, clusters of cells cytologically similar to those of the OSBT were identified in the nodal sinusoids in all four cases and focally in the lymph node parenchyma in three of them. In contrast, the involved lymph nodes of the three cases with delayed nodal disease showed an almost complete replacement by tumor. In one of them, the tumor in the lymph node was histologically similar to the OSBT, while in the other two cases the tumor was more solid and poorly differentiated, suggesting true metastatic disease. Flow cytometric analysis of nuclear DNA content and S-phase fraction were performed on paraffin-embedded tissue of all of the primary OSBTs and of the involved lymph nodes in six cases; diploid DNA content and low S-phase fraction were seen in all cases. All patients were alive and free of disease 2-9 years after initial diagnosis. While the clinical significance of LN involvement in OSBT is still uncertain, DNA ploidy analysis seems to be unable to identify those cases at risk for tumor progression.

Adolescent↗

Late recurrence of clear cell adenocarcinoma of the vagina and cervix: a report of three cases.

Three patients with clear cell adenocarcinomas who developed recurrent disease after a prolonged disease-free interval are presented. The first patient developed a recurrence in the lung 7 years and 3 months after wide local excision and pelvic radiotherapy for clear cell adenocarcinoma of the vagina. She then underwent thoracotomy and chemotherapy and has remained free of disease for more than 13 years after treatment of the recurrence. The second patient with clear cell adenocarcinoma of the vagina developed recurrent disease at the apex of the vagina 5 years after radical hysterectomy, bilateral pelvic lymphadenectomy, and partial vaginectomy. She then underwent exploratory laparotomy, partial vaginectomy, and vaginal irradiation and has been free of disease in follow-up for 6 months. The third patient underwent radical hysterectomy, bilateral pelvic lymphadenectomy, and total vaginectomy for clear cell adenocarcinoma of the cervix that also involved two-thirds of the vagina. Four years and 6 months after this operation, she underwent an exploratory laparotomy, with complete resection of recurrent disease in the abdomen in continuity with a left nephrectomy. Following surgery, she was treated with abdominal and pelvic radiotherapy and chemotherapy and remained clinically free of disease for 1 year, but subsequently developed an unresectable pelvic mass. Despite further chemotherapy, she died 5 years and 10 months after the initial diagnosis.

Abdominal Neoplasms↗

Industry and radiology in Singapore.

Singapore is an ideal educational and commercial hub because of its its central location within Asia, its excellent communication and transportation network, and its ability to remain in the forefront of technology where medical equipment and radiology are concerned. Technologists well trained and fluent in more than one language with an excellent command of English ensures that they benefit from their training stints overseas. From the manufacturer's vantage point, the training center at NUH remains a highly developed center of excellence in Asia, functioning as a shop window for potential clients. Catering to both technologists and radiologists, the center represents the manufacturer's contribution to growth and continued up-grading of the standards in Southeast Asia. We hope that this experiment, the only concrete attempt by any manufacturer in contributing to the radiologic community in Singapore and Southeast Asia, will continue to grow and to develop and become a channel for industry to continue such contributions. One important question that must be addressed is whether all equipment must be purchased from this one manufacturer. There is no such arrangement, and whatever equipment is needed is purchased from any source, depending on budgetary constraints and other restrictions. We believe that training and contributing to the growth, understanding, and application of all modalities in radiology should be worldwide, but organized regionally. In planning training programs, companies must look beyond their countries of origin and rely more heavily on input from their local, regional, and national offices. We hope that the program we have established will serve as a model that can be used elsewhere.

Hospitals, University↗