Acute adrenal insufficiency: an aide-memoire of the critical importance of its recognition and prevention.

Adrenal crisis is a life-threatening emergency that causes significant excess mortality in patients with adrenal insufficiency. Delayed recognition by medical staff of an impending adrenal crisis and failure to give timely hydrocortisone therapy within the emergency department continue to be commonly encountered, even in metropolitan teaching hospitals. Within the authors' institutions, several cases of poorly handled adrenal crises have occurred over the last 2 years. Anecdotal accounts from members of the Addison's support group suggest that these issues are common in Australia. This manuscript is a timely reminder for clinical staff on the critical importance of the recognition, treatment and prevention of adrenal crisis. The manuscript: (i) outlines a case and the clinical outcome of sub-optimally managed adrenal crisis, (ii) summarises the clinical features and acute management of adrenal crisis, (iii) provides recommendations on the prevention of adrenal crisis and (iv) provides guidance on the management of 'sick days' in patients with adrenal insufficiency.

Exome sequencing and array-based comparative genomic hybridisation analysis of preferential 6-methylmercaptopurine producers.

Preferential conversion of azathioprine or 6-mercaptopurine into methylated metabolites is a major cause of thiopurine resistance. To seek potentially Mendelian causes of thiopurine hypermethylation, we recruited 12 individuals who exhibited extreme therapeutic resistance while taking azathioprine or 6-mercaptopurine and performed whole-exome sequencing (WES) and copy-number variant analysis by array-based comparative genomic hybridisation (aCGH). Exome-wide variant filtering highlighted four genes potentially associated with thiopurine metabolism (ENOSF1 and NFS1), transport (SLC17A4) or therapeutic action (RCC2). However, variants of each gene were found only in two or three patients, and it is unclear whether these genes could influence thiopurine hypermethylation. Analysis by aCGH did not identify any unusual or pathogenic copy-number variants. This suggests that if causative mutations for the hypermethylation phenotype exist they may be heterogeneous, occurring in several different genes, or they may lie within regulatory regions not captured by WES. Alternatively, hypermethylation may arise from the involvement of multiple genes with small effects. To test this hypothesis would require recruitment of large patient samples and application of genome-wide association studies.

Prevalence and significance of CYP2C19*2 and CYP2C19*17 alleles in a New Zealand acute coronary syndrome population.

BACKGROUND: High on-treatment platelet reactivity has been associated with poor outcomes following acute coronary syndromes (ACS). Both the loss of function CYP2C19*2 allele and the gain of function CYP2C19*17 allele along with a range of clinical characteristics have been associated with variation in the response to clopidogrel. AIM: The study aims to examine the frequency of CYP2C19 variants and understand the factors associated with on-treatment platelet reactivity in a New Zealand ACS population. METHODS: We prospectively enrolled 312 ACS patients. We collected clinical characteristics and measured on-treatment platelet reactivity using two validated point-of-care assays, VerifyNow and Multiplate. DNA was extracted and CYP2C19*2 and *17 alleles were identified using real-time polymerase chain reaction. RESULTS: CYP2C19*2 or CYP2C19*17 alleles were observed in 101 (32%) and 106 (34%) of patients, respectively, with significant differences in distribution by ethnicity. In Maori and Pacific Island patients, 47% (confidence interval (CI) 31-63%) had CYP2C19*2 and 11% (CI 4-19%) CYP2C19*17 compared with 26% (CI 19-32%) and 41% (CI 32-49%) in white people. Carriage of CYP2C19*2 alleles was associated with higher levels of platelet reactivity measured by either assay, but we observed no relationship between platelet reactivity and CYP2C19*17. In multivariate analysis diabetes, clopidogrel dose and CYP2C19*2 status were all significant independent predictors of platelet reactivity. CONCLUSIONS: Both CYP2C19*2 and *17 were common in a New Zealand ACS population, with CYP2C19*2 observed in almost half the Maori and Pacific Island patients. CYP2C19*2, diabetes and clopidogrel dose were independent contributors to on-treatment platelet reactivity.

Ipilimumab-induced hypophysitis in melanoma patients: an Australian case series.

BACKGROUND: Ipilimumab (Yervoy; Bristol-Myers Squibb) is a novel fully humanised monoclonal antibody that blocks cytotoxic T-lymphocyte antigen 4, an immune checkpoint molecule, to augment anti-tumour T-cell responses. It is associated with significant immune-related side-effects including hypophysitis. AIM: We reviewed the clinical and biochemical characteristics of 10 patients with ipilimumab-induced hypophysitis (IH), and developed guidelines for the early detection and management of IH based on our experiences at three major teaching hospitals in Sydney. METHODS: All patients were evaluated at the Crown Princess Mary Cancer Centre and Department of Endocrinology, Westmead Hospital, Department of Endocrinology, Royal Prince Alfred Hospital, the Melanoma Institute Australia and Macarthur Cancer Therapy Centre, Campbelltown Hospital from 2010 to 2014. Relevant data were extracted by review of medical records. Main outcome measures included clinical features, hormone profile and radiological findings associated with IH, and presence of pituitary recovery. RESULTS: Ten patients were identified with IH. In four patients who underwent monitoring of plasma cortisol, there was a fall in levels in the weeks prior to presentation. The pituitary-adrenal and pituitary-thyroid axes were affected in the majority of patients, with the need for physiological hormone replacement. Imaging abnormalities were identified in five of 10 patients, and resolved without high-dose glucocorticoid therapy. To date, all patients remain on levothyroxine and hydrocortisone replacement, where appropriate. CONCLUSIONS: There is significant morbidity associated with development of IH. We suggest guidelines to assist with early recognition and therapeutic intervention.

Double-burden of malnutrition among the indigenous peoples (Orang Asli) of Peninsular Malaysia.

BACKGROUND: Double-burden of malnutrition (DBM) is an emerging public health concern among the Orang Asli (indigenous peoples) of Peninsular Malaysia. This study aimed to identify the presence of DBM at the community and household levels in Orang Asli population and its associated demographic and socio-economic factors. METHODS: This cross-sectional study was conducted in 11 Orang Asli villages surrounding the Krau Wildlife Reserve, Peninsular of Malaysia from October 2011 to January 2012. Of 438 households, a total of 981 adults and 304 children who met the study criteria agreed to participate. About 160 households were further selected with pairs of children aged 3-59 months and non-pregnant mothers aged 15-55 years. Demographic and socio-economic data were obtained using interviewer-administered questionnaire while weight and height were measured using standard procedures. Double-burden of malnutrition was defined as overweight/obese mother-underweight child (OWOBM/UWC), overweight/obese mother-stunted child (OWOBM/STC) or overweight/obese mother-underweight or/and stunted child (OWOBM/UWSTC). Binary logistic regression identified the demographic and socio-economic factors associated with double-burden households. RESULTS: About 26 % of overweight and obese adults coexisting with high proportions of underweight (49%) and stunted (64%) children in these Orang Asli villages. There was a higher prevalence of households with OWOBM/UWSTC (20%) and OWOBM/STC (19.4%) than households with OWOBM/UWC (12.5%). Boys (P < 0.05), older age mothers (P < 0.05), mothers with higher education (P < 0.05) and households with income per capita less than USD 29.01 (RM 97.00) (P < 0.01) were associated with higher odds of OWOBM/STC. Jah Hut (P < 0.05) and higher number of children (P < 0.05) were significantly associated with lower odds of OWOBM/UWC. CONCLUSIONS: The occurrence of double-burden of malnutrition in Orang Asli population deserves attention. Poverty reduction, access to quality diet and improved health and nutrition literacy are among strategies that could address the coexistence of DBM in this population.

A Comprehensive Clinical Outcome Analysis of Endoscopic Vessel Harvesting for Coronary Artery Bypass Surgery.

Background: The long saphenous vein is routinely used for coronary bypass graft (CABG) surgery, and two primary techniques are commonly utilized: endoscopic vessel harvesting (EVH) and open vessel harvesting (OVH). The aim of this study was to compare the clinical outcomes of the EVH and OVH techniques used for CABG within the confines of a tertiary hospital. Methods: The clinical data of all patients subjected to either EVH or OVH for CABG surgery between 2014 and 2018 were retrospectively analyzed. Statistical analysis was performed to discern variations in the rates of postoperative complications between EVH and OVH. Results: A cohort of 1884 individuals were included in this study, 75.3% of whom underwent EVH. Notably, the incidence of postoperative leg wound complications was significantly different between the patients who underwent OVH and the patients who underwent EVH, with incidence rates of 18.6% and 32%, respectively (p < 0.001). Leg wound complications (p < 0.001; OR 1.946; 95% CI 1.528-2.477) and leg wound infections (p = 0.050, OR 1.517, 95% CI 0.999-2.303) were significantly associated with OVH. Moreover, leg wound hematoma (p = 0.039, OR = 0.402, 95% CI = 0.169-0.957) and EVH were strongly associated. Conclusions: The large sample of patients and the inclusion of a range of Asian ethnic groups provided notable insights into postoperative complications related to different modalities. EVH was associated with a lower incidence of postoperative leg wound complications, which suggests that EVH is a better modality for those undergoing CABG surgery.

Critical analysis of valganciclovir dosing and renal function on the development of cytomegalovirus infection in kidney transplantation.

BACKGROUND: Cytomegalovirus (CMV) infection is one of the most common and important opportunistic infections following kidney transplantation. It causes significant morbidity and mortality. Valganciclovir (VGCV) is the drug of choice for prophylaxis to prevent CMV infection. METHODS: We conducted a post-hoc analysis of a randomized controlled trial in 187 kidney transplant recipients to evaluate the impact of VGCV dosing and renal function on the development of CMV infection. RESULTS AND CONCLUSION: The results demonstrate that the following variables were independent risk factors for the development of CMV infection: high-risk CMV serostatus (donor positive/recipient negative; hazard ratio [HR] 1.4, 95% confidence interval [CI] 1.46-5.28, P = 0.002); anti-thymocyte globulin induction therapy (HR 2.1, 95% CI 1.08-4.07, P = 0.028); higher mean tacrolimus trough concentration (HR 1.4, 95% CI 1.09-1.74, P = 0.007); creatinine clearance <60 mL/min (HR 3.4, 95% CI 1.64-6.85, P = 0.001); and body weight >80 kg (HR 2.1, 95% CI 1.05-4.37, P = 0.037). VGCV dosing was appropriate for most patients, in those who did and did not develop CMV infection. These results strongly suggest that the currently recommended dose adjustments of VGCV dosing based on estimated renal function calculated using ideal body weight may underestimate the renal function of overweight patients and indirectly result in underexposure of overweight patients to VGCV. Based on these findings, further VGCV pharmacokinetic analyses are warranted in kidney transplant recipients with moderate-to-severe renal dysfunction.

Significant bacterial contamination risk reduction with the use of diversion pouch.

BACKGROUND: Significant efforts have been made towards bacterial risk minimization by limiting the chance of bacteria entering into collected blood, detecting its presence and eliminating them by pathogen reduction technology. Improved skin disinfection and the use of diversion pouch are effective upstream measures to reduce the risk of bacterial sepsis. Here we report on our experience with the use of blood bags with diversion pouch. MATERIALS AND METHODS: An observational study was performed to compare the bacterial contamination rate for two periods of time, i.e. before and after introduction of diversion pouch into blood bags. The incidence of bacterial contamination was monitored by the existing bacterial surveillance programme using pooled samples from 5 units of random donor platelets underwent aerobic culture in the BacT/ALERT 3D system. RESULTS: Between 1 June 2004 and 31 May 2006 (blood bag without diversion pouch), 50 (0·0213%) out of 234,252 units of random donor platelets were found to have bacteria on culture whereas 15 (0·0057%) isolates out of 262,156 units were found from 1 June 2007 to 31 May 2009 (after diversion pouch was introduced). Overall, there was an 85% reduction in bacterial contaminated risk due to skin flora (P < 0·0001) but an increasing trend of detection of non skin flora such as Streptococcus bovis was noted. CONCLUSION: Integration of diversion pouch into blood bags to divert the first 30 mL blood during blood collection on top of the current skin disinfection protocol can significantly reduce the risk of bacterial contamination.

Traction-induced aneurysm of an accessory left hepatic artery: a potentially fatal but synchronously treatable complication of a large hiatus hernia.

A 59-year-old man presented to our surgical clinic with a long-standing history of heart burn, and upper abdominal pain. Gastroscopy showed a large sliding hiatus hernia associated with severe reflux oesophagitis. Oesophageal pH manometry revealed a high DeMeester score of 36.03. A computed tomography (CT) scan was performed for preoperative hiatal hernia repair planning. This showed the incidental finding of an accessory left hepatic artery (ALHA) and an aneurysm of this accessory artery. The aneurysm occurred at the point where the ALHA traversed the diaphragmatic crus and was only present in association with the hiatus hernia. These observations suggest that the aetiology of the aneurysm was due to traction during development of the hiatus hernia. The patient went onto have a laparoscopic hiatus hernia repair and Toupet fundoplication with ligation of the accessory left hepatic artery and made an excellent recovery. ALHAs are not uncommon, occurring in around 15% of the general population, with aneurysms of the hepatic arteries accounting for about 20% of cases of visceral artery aneurysms. The case presented herein highlights the importance of performing an arterial phase CT when planning surgery for large hiatus hernias to detect more cases like this one. This would allow early detection and concurrent treatment of an associated aneurysm with repair of the hiatus hernia, to prevent aneurysmal complications later on.

Can the measured angle ABC on the lateral projection of the knee be used to determine the tube angulation for an optimum skyline projection?

INTRODUCTION: The current technique of angulating for a skyline knee projection relies heavily on the radiographer's estimation of the patella tilt, rendering it subjective and prone to errors. This study therefore aims to (i) examine the correlation between angle ABC measured on the lateral X-ray image and skyline angulation (measured in degrees) and (ii) determine the inter-rater reliability of angle ABC measurements. METHODS: 145 sets of lateral and skyline X-ray images from patients aged 40-70 years old were retrospectively analysed. Angle ABC was measured using prominent landmarks such as the trochlear sulcus, tibial tuberosity and the anterior border of the patella on the lateral knee radiograph. It was then retrospectively compared with the skyline tube angulations to identify any correlation between the two. An inter-rater reliability test was also conducted using the intraclass correlation coefficient (ICC) to determine the reproducibility of the measurement method. RESULTS: A weak correlation was found between angle ABC and skyline angulation (r = 0.1, p = 0.25). The proposed method of measurement shows good inter-rater reliability (ICC = 0.81, 95% CI: 0.77 to 0.84). CONCLUSION: There is insufficient evidence to indicate a correlation between angle ABC and skyline angulation. However, angle ABC can be reliably measured, implying the replicability of the measurement method for other purposes. IMPLICATIONS FOR PRACTICE: The proposed measurement method of angle ABC on the lateral view could have future applications in other areas such as in the measurement of patellofemoral alignment and trochlear morphology.

The danger of using inappropriate point-of-care glucose meters in patients on icodextrin dialysis.

AIMS: Icodextrin is a glucose polymer used to maintain an osmotic gradient in peritoneal dialysis. Metabolites of icodextrin are known to cause overestimation of blood glucose in glucose meters using glucose dehydrogenase/pyrroloquinolinequinone systems. The aim of this study is to determine the extent of icodextrin interference in glucose meters using the newer glucose dehydrogenase/NAD or glucose oxidase systems. This has not been established previously. METHODS: Fasting blood samples (n = 4) were spiked with either one icodextrin metabolite (maltose, maltotriose or maltotetraose) or a combination, at various blood concentrations expected during dialysis. Samples were tested in triplicate on: five glucose-meters, a Radiometer® (glucose oxidase/hydrogen peroxide) and laboratory (hexokinase) analysers. Each meter was also tested on blood from six patients undergoing dialysis. Accuracy was evaluated as % Bias = [(meter glucose - laboratory glucose)/laboratory glucose] × 100. RESULTS: A single icodextrin metabolite affected glucose measurements and, in combination, the interferences were additive in the two Accu-Chek® and Optium® Xceed meters by > 10%. Amongst these meters, the Optium Xceed 5-s machine was less affected. Meters using glucose oxidase were least affected by interference. A similar trend in interference was observed in vivo. CONCLUSION: While meters using glucose dehydrogenase/NAD are less affected by icodextrin metabolites, interference can still be demonstrated. The degree of interference can vary in different glucose meters using this enzyme/cofactor system, as seen in the Optium Xceed machines. Icodextrin is an important source of interference that sometimes even experienced professionals are unaware of and which leads to clinically significant errors in insulin dose adjustment. Awareness of this interference and selection of the most appropriate glucose meters are crucial to minimize this hazard.

Value of anaerobic culture in bacterial surveillance program for platelet concentrates.

BACKGROUND: Short-term aerobic bacterial culture (STABC) has been used routinely in Hong Kong since 1998 to reduce bacterial contamination in platelet concentrates (PCs) with good results. With more countries implementing routine aerobic and anaerobic cultures of PCs, a prospective study was conducted to determine the value of anaerobic culture to STABC. STUDY DESIGN AND METHODS: PC tested by STABC was used as control. Twenty milliliters of the PC selected for this study was aliquoted and pooled for 7 days aerobic and anaerobic culture. If the initial culture was positive, samples retrieved from the original PC and their associated components were cultured for confirmation and microbiologic identification. RESULTS: A total of 10,035 PC units (2007 pools) were tested. The confirmed positive rates by aerobic and anaerobic cultures per pool were 3 (0.15%) and 13 (0.65%), respectively, which was equivalent to an increased yield from 0.03 to 0.13 percent of PC if anaerobic culture was added. Of the 10 bacteria detected by anaerobic culture only, 9 were found to be Propionibacterium acnes and the remaining one Peptostreptococcus sp. Their mean detection time from inoculation was 92.16 hours (range, 50.4-124.8 hr). CONCLUSION: Addition of anaerobic culture to our routine STABC would significantly increase the detection rate of bacterial contaminated PC. However, since only slow-growing bacteria were detected, and because their clinical significance was uncertain, it is concluded that there was no clear justification to introduce anaerobic culture locally if 5-day shelf life for PCs was to be maintained.

Genetic analysis of SCA2, 3 and 17 in idiopathic Parkinson's disease.

Recent reports of SCA2 and SCA3 patients who presented with levodopa responsive parkinsonism have generated considerable interest as they have implications for genetic testing. It is unclear whether ethnic race alone or founder effects within certain geographical region explain such an association. In this study, we conducted genetic analysis of SCA2, 3, 17 in an ethnic Chinese cohort with early onset and familial Parkinson's disease (PD) and healthy controls. A total of 191 subjects comprising of 91 PD and 100 healthy controls were examined. We identified one positive case of SCA2 in an early-onset sporadic PD patient who had CAG 36 repeats, yielding a prevalence of 2.2% in early-onset sporadic PD patients and less than 1.0% in our study PD population. The size of the repeats was lower than the expanded repeats (38-57) in SCA2 patients with ataxia in our population. All the children of the patient were physically normal even though some of them carried the repeat expansion of similar size. No cases and controls were positive for SCA3 and SCA17. We do not think routine screening of SCA2, SCA3 and SCA17 for all idiopathic PD patients is cost-effective in our ethnic Chinese population. However, SCA2 should be a differential diagnosis in young onset sporadic PD when genetic mutations of other known PD genes have been excluded.

Elevated serum thyroglobulin levels at the time of ablative radioactive iodine therapy indicate a worse prognosis in thyroid cancer: an Australian retrospective cohort study.

BACKGROUND: Serum thyroglobulin is used as a surrogate marker for well-differentiated thyroid carcinoma recurrence. This study investigates whether thyroglobulin measured at the time of ablative radioactive iodine therapy predicts disease-free survival. METHODS: A retrospective review was conducted of patients with well-differentiated thyroid carcinoma presenting from 1989 to 2010 at the Royal Prince Alfred Hospital, New South Wales, Australia. Disease-free survival of patients with a significantly elevated stimulated thyroglobulin level (27.5 µg/l or higher) at the time of ablative radioactive iodine therapy was compared to that of patients without a significantly elevated thyroglobulin level using univariate analysis. RESULTS: Patients with a thyroglobulin level of 27.5 µg/l or higher had an increased relative risk of disease recurrence of 4.50 (95 per cent confidence interval = 1.35-15.04). If lateral neck dissection was required at the time of surgery, patients also had an increased relative risk of macroscopic disease recurrence of 4.94 (95 per cent confidence interval = 1.47-16.55). CONCLUSION: An elevated thyroglobulin level of 27.5 µg/l or higher at the time of ablative radioactive iodine therapy is a prognostic indicator for macroscopic disease recurrence in well-differentiated thyroid carcinoma.

Albumin Church Bay: 560 Lys-->Glu a new mutation detected by electrospray ionisation mass spectrometry.

Albumin Church Bay is a fast migrating genetic variant of human serum albumin which, in a heterozygous subject, formed about 50% of the circulating albumin. Reversed phase peptide mapping and electrospray ionisation mass spectrometry (ESI-MS) indicated that the C-terminal CNBr peptide had decreased polarity associated with a 1 Da increase in mass. Subdigestion of this peptide with trypsin and chymotrypsin revealed that the increased mass was associated with the chymotrypsin fragment VEKCCKADDKETCF (555-568) which had a mass of 1791.1 compared to 1790.2 for its normal counterpart. Sequence analysis of PCR-amplified DNA indicated an A-->G mutation at position 98 of exon 13, which causes a point mutation of 560 Lys-->Glu and results in a 1 Da mass increase.

The G2019S LRRK2 mutation is uncommon in an Asian cohort of Parkinson's disease patients.

A common heterozygous leucine-rich repeat kinase 2 (LRRK2) mutation 6055G > A transition (G2019S) accounts for about 3-7% of familial Parkinson's disease (PD) and 1-1.6% sporadic PD in a number of European populations. To determine the prevalence of the G1019S mutation in our Asian population, we conducted genetic analysis of this mutation in 1000 PD and healthy controls. The G2019S mutation was not detected in any of our study subjects. The prevalence of G2019S mutation is rare (< 0.1%) in our population, suggesting that occurrence of this mutation may vary amongst different ethnic races. This has important clinical implication when implementing guidelines for genetic testing.

Prevalence and distribution of ret/ptc 1, 2, and 3 in papillary thyroid carcinoma in New Caledonia and Australia.

The world's highest incidence of thyroid cancer has been reported among females in New Caledonia, a French overseas territory in the Pacific located between Australia and Fiji. To date, no molecular genetic studies in this population are available. Over the past few years, the oncogenic rearrangement of the ret protooncogene (ret/ptc) has been studied in papillary carcinomas in different populations. In this study, we investigated the prevalence and distribution of ret/ptc1, 2, and 3 in papillary thyroid carcinoma from the New Caledonian population and compared the pattern with that of an Australian population. Fresh-frozen and paraffin-embedded papillary carcinomas from 27 New Caledonian and 20 Australian patients were examined for ret rearrangements by means of RT-PCR with primers flanking the chimeric region, followed by hybridization with radioactive probes. ret/ptc was present in 70% of the New Caledonian and in 85% of the Australian samples. Multiple rearrangements were detected and confirmed by sequencing in 19 cases, 4 of which had 3 types of rearrangements in the same tumor. This study demonstrates a high prevalence of ret/ptc in New Caledonian and Australian papillary carcinoma. The findings of multiple ret/ptc in the same tumor suggest that some thyroid neoplasms may indeed be polyclonal.

Fulminant hepatic failure in non-Hodgkin lymphoma patients treated with chemotherapy.

Chemotherapy is the mainstay of therapy for patients with non-Hodgkin lymphoma. Among side-effects associated with the use of chemotherapy, immunosuppression is one which can be potentially fatal. In hepatitis B carriers, immunosuppression permits widespread infection of the hepatocytes and its subsequent withdrawal causes an "immunological rebound" leading to massive necrosis of hepatocytes. 4 patients who died of fulminant hepatitis following chemotherapy are reported. These were patients with positive hepatitis B serology. Caution is advised when treating non-Hodgkin lymphoma in patients from hepatitis B endemic regions.

Concurrent chemoradiotherapy followed by adjuvant chemotherapy in Asian patients with nasopharyngeal carcinoma: toxicities and preliminary results.

PURPOSE: Nasopharyngeal carcinoma (NPC) is endemic in Singapore. Nearly 60% of the patients diagnosed with NPC will present with locally advanced disease. The North American Intergroup study 0099 reported improved survival outcome in patients with locally advanced NPC who received combined chemoradiotherapy when compared to radiotherapy alone. Hence we explored the feasibility and efficacy of a similar protocol in our patients. METHODS AND MATERIALS: Between June 1996 and December 1997, 57 patients were treated with the following schedule as described. Radical radiotherapy (RT) of 66-70 Gy to the primary and neck with cisplatin (CDDP) 25 mg/m2 on days 1-4 given by infusion over 6-8 hours daily on weeks 1, 4, and 7 of the RT. This is followed by a further 3 cycles of adjuvant chemotherapy starting from week 11 from the first dose of radiation (CDDP 20 mg/m2/d and 5-fluorouracil [5-FU] 1 gm/m2/d on days 1-4 every 28 days). RESULTS: The majority of patients (68%) had Stage IV disease. About 54% of patients received all the intended treatment; 75% received all 3 cycles of CDDP during the RT phase and 63% received all three cycles of adjuvant chemotherapy. The received dose intensity of CDDP and 5-FU of greater than 0.8 was achieved in 58% and 60% of the patients respectively. Two treatment-related deaths due to reactivation of hepatitis B and neutropenic sepsis respectively, were encountered. At median follow-up of 16 months, 14 patients had relapsed, 12 systemically and 2 loco-regionally. CONCLUSION: Due to the acceptable tolerability of such a protocol in our cohort of patients, we have embarked on a Phase III study to confirm the results of the 0099 Intergroup study in the Asian context.