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Biomedical subjects

L T Tan

Publications and source records attributed to L T Tan.

At least 19 recordsLinked to original sources
PubMed2004

Acute toxicity of chemo-radiotherapy for cervical cancer: the Addenbrooke's experience.

AIMS: An audit of acute treatment-related toxicity during chemo-radiotherapy for cervical cancer was carried out to assess its tolerance outside research settings. MATERIALS AND METHODS: Between May 1999 and April 2003, 74 patients with carcinoma of the cervix were treated with radical radiotherapy given concurrently with weekly cisplatin chemotherapy. Fifty-nine (79.7%) patients received chemo-radiotherapy as primary radical treatment, 10 (13.5%) patients were treated adjuvantly for poor-prognosis features after radical surgery, and the remaining five (6.8%) were given chemo-radiotherapy for pelvic recurrences after previous surgery. Acute treatment-related toxicity was graded prospectively at weekly intervals during chemo-radiotherapy using the National Cancer Institute Common Toxicity Criteria. RESULTS: The most common adverse effects were diarrhoea (80.6%), malaise (66.7%) and nausea (62.5%). The most common haematological toxicity was anaemia, with 41.7% patients developing grade 1 or 2 toxicity. Only three (4.2%) patients had grade 3 or 4 toxicity. One patient had grade 3 thrombocytopenia, another had grade 4 neutropenia and the third patient had grade 3 diarrhoea. A statistically significant correlation was found between maximum treatment-related toxicity, larger treatment volumes (P = 0.006) and disease stage (P = 0.04). A total of 97.3% of patients completed external beam radiotherapy without any interruptions for treatment-related toxicity. Only two patients (3.4%) experienced a delay in brachytherapy for treatment-related toxicity. Two patients died during external beam radiotherapy, and one patient suffered a fatal pulmonary embolism 1 week after completing brachytherapy treatment. A total of 70.2% patients completed the planned number of chemotherapy cycles, with a further 20.3% receiving at least three cycles. The most common reason for failure to complete chemotherapy as planned was gastrointestinal toxicity. There was no correlation between failure to complete planned chemotherapy and patient age, disease stage, radiotherapy treatment volumes or postoperative treatment. CONCLUSION: Our study has shown that cisplatin-based chemo-radiotherapy for carcinoma of the cervix is well tolerated when given to a largely unselected population of patients outside research settings. The effectiveness of the treatment should therefore mirror the efficacy obtained in clinical trials.

Adenocarcinoma↗
PubMed2003

An audit of delays before and during radical radiotherapy for cervical cancer--effect on tumour cure probability.

AIM: To evaluate the potential impact of time delay before and during radical radiotherapy for cervical carcinoma at Addenbrooke's Hospital. MATERIALS AND METHODS: An audit was undertaken which recorded the number of gaps during external beam radiotherapy (EBRT), overall treatment time, and delay between first oncology consultation to start of radiotherapy, for patients receiving primary radical radiotherapy for cervical cancer in 1996, 1998 and 2001. Radiobiological modelling was used to calculate the tumour control probability (TCP). A questionnaire survey of 62 oncology departments in the U.K. was carried out for comparison. RESULTS: The percentage of patients completing EBRT without any interruptions was 22, 67 and 94% in 1996, 1998, and 2001, respectively (P = 0.0009). The median overall treatment time was 49, 42 and 39 days in 1996, 1998 and 2001, respectively (P = 0.001). However, the median waiting time to start of radiotherapy increased from 14 days in 1996 to 18 days in 1998 and 35 days in 2001 (P = 0.007). CONCLUSION: The results from the national survey showed that this pattern of improved overall treatment times accompanied by deterioration in waiting times was also seen in most other U.K. centres. Radiobiological modelling showed that any potential gain in TCP resulting from shorter overall treatment times could be offset entirely by the adverse effect of increasing waiting times. The calculations suggest that the tumours most likely to be adversely affected by long waiting times are those with shorter volume doubling times or a medium chance of tumour control at the outset of treatment. A system of patient triage, and prioritization of patients deemed most likely to benefit from a reduced waiting time, may be necessary in the current climate of limited radiotherapy resources.

Appointments and Schedules↗
PubMed2003

Brachiocephalic-superior vena cava metallic stenting in malignant superior vena cava obstruction.

INTRODUCTION: We studied the effectiveness of unilateral brachiocephalic (BC)-superior vena cava (SVC) metallic stent therapy in malignant SVC obstruction. MATERIALS AND METHODS: From November 1998 to February 2002, SVC stenting was performed in 11 patients with symptomatic malignant SVC obstruction. There were 10 males and 1 female, with a mean age of 64.2 years (range, 37 to 78 years). The computed tomography (CT) scan and superior vena cavogram findings of all patients showed malignant SVC obstruction. Both internal jugular veins were patent in all patients by ultrasound. SVC stenting was performed with Wallstent (Boston Scientific, Minneapolis, MN, USA) in 10 patients and Memotherm stent (Bard angiomed, Wachhausstrasse, Germany) in 1 patient. Pressure gradient, duration of the procedure, peri-procedural morbidity and mortality and the general well-being of the patients were reviewed. RESULTS: SVC stenting was performed at a mean duration of 9.6 days (range, 3 to 30 days) after presentation. All were technically successful with 10 across the right BC-SVC and 1 across the left BC-SVC. There was no peri-procedural morbidity or mortality. The entire procedure was completed at a mean duration of 115 minutes (range, 75 to 225 minutes) with good angiographic and pressure results. Immediate symptomatic relief of SVC syndrome was achieved in 10 patients who had received prompt work-up and stenting 3 to 18 days after presentation. The remaining patient, who received work-up and stenting 30 days after presentation, remained dyspnoeic and died of pneumonia 7 days after the procedure. CONCLUSION: Unilateral BC-SVC metallic stenting is an effective measure in malignant SVC obstruction. Prompt pre-stenting work-up and stenting are recommended to achieve a longer symptomatic relief period.

Adult↗
PubMed2001

An audit of clinic consultation times in a cancer centre: implications for national manpower planning.

A departmental audit was conducted to assess the frequency, extent and causes of late completion of oncology clinics. Data were collected prospectively from clinical, medical, haematological and multidisciplinary oncology clinics. The data recorded included: clinic start and finish times, number of patients seen, type of consultation, number of doctors in each clinic, time spent by the doctor with the patient, and other factors that may have contributed to the late completion of clinics. A total of 848 patient consultations were recorded in 81 clinics. Of 67 clinics in which the finish time was recorded, 19 (28%) were completed on time, while 48 (72%) were late by a mean time of 49 minutes. The mean time spent by consultants with new, follow-up and chemotherapy patients was 37, 21 and 22 minutes respectively. This did not include time spent reviewing notes, dictating or ordering investigations. There was no significant difference in the time spent by specialist registrars compared with consultants, or clinical oncologists compared with medical oncologists and haematologists. The incidence of unforeseen problems such as difficult consultations, missing information, unplanned interruptions, late starts and overbooking of patients were not significantly different in those clinics that finished late compared with those that finished on time. The mean overrun of multidisciplinary clinics was longer than for non-multidisciplinary clinics (59 and 31 minutes respectively), despite a higher ratio of doctors to patients in the former (1:5.4 and 1:7 respectively). This audit showed that the main cause of late finishes in clinics in our department was the longer than anticipated time spent by doctors with patients. Consultations are taking longer because of the increasing complexity of non-surgical cancer treatments and the greater emphasis placed on patient information and informed consent. The Royal College of Radiologists (RCR) has calculated that, if a consultant oncologist sees a maximum of 315 new patients per year, the time available for each follow-up consultation would be 10 minutes. Our audit showed that follow-up consultations took an average of 21 minutes. These results suggest that the RCR recommendations for consultant expansion substantially underestimates the true number of consultants required for the treatment of cancer patients in the UK.

Cancer Care Facilities↗
PubMed2001

Treatment of localized carcinoma of the penis: a survey of current practice in the UK.

Consensus opinion from published reports on the management of localized carcinoma of the penis recommends that patients with small, distal, non-poorly differentiated lesions should be offered penis-conserving treatment, while those with larger or more advanced lesions should be considered for amputative surgery. A questionnaire survey was sent to 289 urologists and 237 oncologists in the UK to assess their practice for the treatment of localized carcinoma of the penis. Consultants were asked to choose between penis-conserving surgery, amputation or radiotherapy as their preferred treatment for four examples of localized disease. Oncologists were also asked to indicate their preferred radiation modality (external beam radiotherapy or brachytherapy). For treating a small lesion situated distally on the glans penis, 56.7% of urologists and 94.5% of oncologists preferred penis-conserving methods; 28.8% of urologists and one oncologist preferred partial or total amputation. In total, 43.2% of urologists would consider amputative surgery for this lesion compared with only 5.5% of oncologists. Only 23.3% of oncologists considered using brachytherapy. For a 4 cm lesion situated distally, the majority of urologists surveyed (82.0%) preferred amputative surgery, while the majority of oncologists (68.5%) preferred conservative treatment. For a 1.5 cm lesion extending on to the penile shaft, 68.5% of urologists preferred amputative surgery while 85.0% of oncologists preferred penis-conserving options. For a 4 cm lesion extending on to the shaft, the vast majority of urologists (86.5%) preferred amputation as treatment compared with only 36.9% of oncologists. The results of the survey suggested that clinicians tended to favour the treatment modality of which they have most experience. As such, urologists tended to prefer surgery while clinical oncologists tended to prefer radiotherapy, irrespective of the size and position of the primary tumour or consensus opinion. These results emphasize the importance of multidisciplinary clinics and site specialization, so that both clinicians and patients can make informed choices about optimal treatment, based on the knowledge of all available treatment options.

Carcinoma↗
PubMed2000

cis,cis- and trans,trans-ceratospongamide, new bioactive cyclic heptapeptides from the Indonesian red alga Ceratodictyon spongiosum and symbiotic sponge Sigmadocia symbiotica.

Chemical investigation of the marine red alga (Rhodophyta) Ceratodictyon spongiosum containing the symbiotic sponge Sigmadocia symbiotica collected from Biaro Island, Indonesia, yielded two isomers of a new and bioactive thiazole-containing cyclic heptapeptide, cis,cis-ceratospongamide (1) and trans, trans-ceratospongamide (2). Isolation of these peptides was assisted by bioassay-guided fractionation using a brine shrimp toxicity assay (Artemia salina). The structures of the ceratospongamides, which each consist of two L-phenylalanine residues, one (L-isoleucine)-L-methyloxazoline residue, one L-proline residue, and one (L-proline)thiazole residue, were established through extensive NMR spectroscopy, including (1)H-(13)C HMQC-TOCSY, and (1)H-(15)N HMBC experiments, as well as chemical degradation and chiral analysis. cis,cis- and trans,trans-ceratospongamide are stable conformational isomers of the two proline amide bonds. Molecular modeling of these two ceratospongamide isomers showed the trans, trans isomer to be quite planar, whereas the cis,cis isomer has a more puckered overall conformation. trans,trans-Ceratospongamide exhibits potent inhibition of sPLA(2) expression in a cell-based model for antiinflammation (ED(50) 32 nM), whereas the cis,cis isomer is inactive. trans,trans-Ceratospongamide was also shown to inhibit the expression of a human-sPLA(2) promoter-based reporter by 90%.

Animals↗
PubMed2000

Hermitamides A and B, toxic malyngamide-type natural products from the marine cyanobacterium Lyngbya majuscula.

A Papua New Guinea collection of the marine cyanobacterium Lyngbya majuscula yielded two new and toxic natural products, hermitamides A (1) and B (2). The hermitamides were isolated using a brine shrimp (Artemia salina) toxicity assay. Planar chemical structures of 1 and 2 were established through 1D and 2D NMR, as well as FABMS data. Semisyntheses of hermitamides A (1) and B (2) were achieved by coupling the acid chloride derivative of 7(S)-methoxytetradec-4(E)-enoic acid (4), obtained from the same cyanobacterium collection, and the respective free amines, phenethylamine and tryptamine. Hermitamides A (1) and B (2) exhibited LD(50) values of 5 microM and 18 microM in the brine shrimp bioassay, and an IC(50) values of 2.2 microM and 5.5 microM to Neuro-2a neuroblastoma cells in tissue culture, respectively. Hermitamide A was mildly ichthyotoxic to goldfish, with an LD(50) value of 19 microM, while hermitamide B was inactive at 25 microM.

Amides↗
PubMed2000

Radiation-induced malignant melanoma of the cervix.

We report the occurrence of a malignant melanoma of the uterine cervix in a patient previously irradiated for a squamous cell carcinoma of the cervix. The management of malignant melanoma of the cervix is reviewed. The risk of second cancers in general, malignant melanoma in particular, after radiotherapy for cervical cancer is also discussed.

Aged↗
PubMed2000

Philadelphia positive acute lymphoblastic leukaemia (ALL): clinico-haematologic characteristics, molecular analyses and 3-year follow up--a single institution study.

INTRODUCTION: The Philadelphia chromosome is one of the commonest chromosomal aberration in adult acute lymphoblastic leukaemia (ALL) patients. We present the results of a 3-year prospective study to look at the clinico-haematologic, immunophenotypic, cytogenetic and molecular profile of 13 adult patients with Philadelphia (Ph) positive ALL out of 35 newly diagnosed ALL seen at our institution over the past 3 years. MATERIALS AND METHODS: Thirty-five adult ALL patients seen between 1996 and 1998 comprised the study group. Marrow samples were obtained for immunophenotyping and karyotypic analysis at diagnosis. Samples were also obtained simultaneously for molecular testing for Ph chromosome. RESULTS: Thirteen patients were found to be Ph positive by molecular analysis while cytogenetic studies identified the chromosomal abnormality in 9 of these patients. The median age of our Ph positive patients was similar to those without Ph chromosome. Pre-B phenotype appears to be common in this group of patients. In concordance with other studies, Ph positive ALL was associated with a poor prognosis in our patients. CONCLUSION: Identification of Ph chromosome is important in the management of patients with ALL as it is an important prognostic marker.

Adolescent↗
PubMed1999

Determination of tumour regression rates during radiotherapy for cervical carcinoma by serial MRI: comparison of two measurement techniques and examination of intraobserver and interobserver variability.

Tumour regression rates of 11 patients with cervical carcinoma were estimated during external beam radiotherapy (EBRT) using serial MRI (average time interval 7 days; range 3-15 days). An average of five investigations (range 4-8) was performed per subject. Tumour volume was measured by two observers using the Cavalieri method of modern design stereology in combination with (a) planimetry and (b) point counting. The mean precision of all the volume estimates obtained by manually tracing the outline of the tumour was 6.6%. The mean precision obtained by counting an average of 176 points per investigation on the same transects was 6.7%. The intraobserver repeatability of planimetry, interobserver reproducibility of planimetry and point counting were excellent with no significant difference between the volume estimates obtained using either technique. Based on the planimetry measurements, initial tumour volumes ranged from 6.5 to 222 cm3 (mean 63 cm3, median 44 cm3). Based on the point counting measurements, initial tumour volumes ranged from 7.2 to 235 cm3 (mean 68 cm3, median 46 cm3). Tumour regression began within a few days of commencing EBRT and showed an exponential relationship with time (p < 0.01). There was good agreement between the regression rates obtained by planimetry and those obtained by point counting. No significant correlation was found between initial tumour volume and tumour regression rate for either planimetry or point counting. Planimetry measurements were, on average, obtained in about half the time taken for point counting (i.e. 30 min and 50 min, respectively). Although point counting is generally likely to be the more efficient approach, planimetry may be the preferred approach for estimating tumour volume when a purpose built track ball is available and the tumour morphology is relatively simple. Volume measurement should be obtained using the Cavalieri method to ensure that the estimates are unbiased and that their precision can be predicted. The measured tumour regression rates may have important implications for improving local tumour control, optimum timing of brachytherapy and minimizing the risk of radiation damage.

Adult↗
PubMed1999

Contrast enhanced dynamic MRI of cervical carcinoma during radiotherapy: early prediction of tumour regression rate.

This prospective study investigated the relationship between changes in the MRI dynamic enhancement of cervical carcinoma early during radiotherapy, and tumour regression rate throughout radiotherapy. A total of 36 MRI examinations was performed in seven patients with cervical carcinoma, including a T2 weighted sequence weekly during radiotherapy and also a multislice dynamic Gd-DTPA enhanced sequence before and after the first 2 weeks of radiotherapy. Tumour enhancement was determined on dynamic images using a region of interest and signal-to-noise ratio method. Serial tumour volumes over time on T2 weighted images were estimated using the Cavalieri method of modern design-based stereology to obtain tumour regression rate. It was found that peak and mean enhancement prior to radiotherapy ranged from 3.0 to 13.3, and from 1.9 to 12.2, respectively. After 2 weeks of radiotherapy, peak and mean enhancement ranged from 7.5 to 13.0, and from 6.3 to 10.6, respectively. The change in peak and mean tumour enhancement between dynamic scans ranged, respectively, from -2.0 to 8.4 and from -4.5 to 8.5. Tumour volume decreased exponentially with time (p < 0.01). Tumour regression rates ranged from 2.0% to 15.2% per day, and correlated positively with changes of both peak and mean tumour enhancement (p < 0.01). It is concluded that MRI dynamic enhancement during the first 2 weeks of radiotherapy may provide early prediction of tumour regression rate, and therefore be of value in designing treatment schedules for cervical carcinoma.

Adult↗
PubMed1999

Molecular and phenotypic spectrum of de novo Philadelphia positive acute leukemia.

The Philadelphia chromosome is present in a heterogeneous group of leukemias. It is most commonly associated with chronic myelogenous leukemia (CML) and B-lineage acute lymphoblastic leukemia (ALL) being found in more than 95% and 15-25% of cases respectively. We undertook a study to determine the morphologic, phenotypic and molecular diversity of Philadelphia positive de novo acute leukemia patients seen at our institution over the past 3 1/2 years. Twenty-one patients with de novo acute leukemia were found to have the Philadelphia chromosome by cytogenetic studies. They consisted of 3 patients with acute myelogenous leukemia (AML), 1 biphenotypic leukemia and 17 ALL patients. Of the patients with ALL, 16 were of B-lineage while 1 had a T-cell phenotype. Ten patients expressed the p210 BCR-ABL transcript alone and 10 expressed only the p190 BCR-ABL transcript. One patient had co-expression of p190 and p210 b3a2 BCR-ABL transcripts. Thus the Philadelphia chromosome can be found in a diverse cohort of morphologic and immunologic subtypes of de novo acute leukemia reflecting the heterogeneity of lineage involvement in this disease.

Acute Disease↗
PubMed1999

Two patients with novel BCR/ABL fusion transcripts (e8/a2 and e13/a2) resulting from translocation breakpoints within BCR exons.

We have identified novel BCR-ABL mRNA fusions by RT-PCR in two patients with Philadelphia (Ph) chromosome positive leukaemia. Sequencing revealed in-frame fusions consisting of part of BCR exon e8 spliced to ABL exon a2 in one patient and part of BCR exon e13 spliced to ABL exon a2 in the other. The breaks within BCR exons e8 and e13 did not conform to consensus splice sites, suggesting that the aberrant fusion mRNAs may have arisen as a result of translocation breakpoints at these sites. This was confirmed by genomic DNA bubble PCR for the second patient. These data show that BCR-ABL translocation breakpoints can occasionally occur within coding exons.

Adult↗
PubMed1997

Radical radiotherapy for carcinoma of the uterine cervix using external beam radiotherapy and a single line source brachytherapy technique: the Clatterbridge technique.

At the Clatterbridge Centre for Oncology, a single line source brachytherapy technique using the Selectron (Nucletron) low dose rate remote afterloading equipment has been developed for use in conjunction with homogenous whole pelvis external beam radiotherapy in the radical treatment of carcinoma of the cervix. The technique incorporates several modifications aimed at reducing treatment related morbidity while maintaining satisfactory local tumour control and cure rates. A flexible dose prescription system has been devised to allow individualization of the brachytherapy isodose distribution according to the clinical findings and the estimated normal tissue doses. Modifications of source loading distributions are carried out to limit the point "A" dose rate to a narrow range to take into account the dose rate effect on the risk of complications. Source loading distributions are also modified according to the estimated normal tissue doses in order to respect normal tissue tolerance. This paper describes the technique and its underlying principles.

Brachytherapy↗
PubMed1997

An audit of the treatment of carcinoma of the uterine cervix using external beam radiotherapy and a single line source brachytherapy technique.

A single line source brachytherapy (BT) technique has been developed at Clatterbridge to boost the dose to the primary tumour after whole pelvis external beam radiotherapy (EBRT) for the radical treatment of carcinoma of the cervix. 226 patients with invasive carcinoma of the uterine cervix were treated with radiotherapy alone using this technique (median age 57 years; range 25-87 years). 49 patients had Stage IB disease, 97 had Stage II, 73 had Stage III and seven patients had biopsy confirmed Stage IVA disease. Patients with low bulk disease were given 40-42.5 Gy in 20 fractions while those with bulky disease received 45 Gy in 20 fractions or 50 Gy in 25 fractions. On completion of EBRT, 186 patients (82.3%) proceeded to intracavitary BT using a linear arrangement of sources with the Selectron (Nucletron) remote afterloading unit. Most of the patients (137/226, 60.6%) received a single insertion of 20 Gy to point "A", at a preferred dose rate within the range 0.95-1.05 Gy h-1. In another 30 patients (13.3%), BT was possible at a later date after further tumour regression. Only 10 patients (4.4%) did not receive BT as part of their treatment. The 5 year actuarial cause-specific survival rate was 79% in Stage I disease, 61% in Stage II, 31% in Stage III and 71% in the small number of patients with Stage IVA disease. The 5 year pelvic control rates were 88% for Stage I, 69% for Stage II, 45% for Stage III and 71% for Stage IVA. Significant prognostic variables for survival and local pelvic control on univariate analysis included disease stage, patient age, tumour bulk, nodal status, anaemia, renal failure and overall treatment time. Tumour grade was a significant prognostic variable for survival but not for local tumour control. The extent of parametrial involvement was a significant prognostic variable for survival and local control for Stage IIB but not for Stage IIIB. There was a statistically significant decrease in survival and local tumour control for patients receiving > or = 70 Gy to point "A", or > or = 55 Gy to point "B". On multivariate analysis, the independent prognostic variables for survival and local control were disease stage, overall treatment time and renal failure. Patient age was also an independent prognostic variable for survival while nodal status was an independent prognostic variable for local control. A high proportion of the patients had adverse prognostic features resulting in a very high actuarial risk of distant metastases of 38.1% at 5 years (68.8% for Stage III patients). The overall treatment time was significantly longer in Stage III patients compared with Stage I and Stage II patients. The actuarial rate of Grade 2 late radiation morbidity was 2.7% and 4.3% for the urinary tract and bowel respectively while that of Grade 3 morbidity was only 0.6% and 1.4%, respectively. Good local control can be achieved for patients with nonbulky tumours using relatively low biological doses while minimizing the risk of late treatment related toxicity. Several changes in treatment policy have been made in an attempt to improve local tumour control and possibly survival, particularly for Stage III patients and patients with bulky disease.

Adult↗