Use of monoclonal antibody E48 in diagnosing transitional cell carcinoma of urinary bladder.

AIMS: To investigate the localisation of the E48 epitope and to determine the use of monoclonal antibody E48 for the identification of transitional cell carcinomas (TCC); and to determine if antigenic expression was affected by different standard fixation methods. METHODS: Biopsy specimens were labelled with E48 for immunoelectron microscopy. One hundred and nineteen tissue samples from 47 bladder carcinomas were tested for reactivity with E48, using fresh frozen, sublimate formalin, and formalin fixed tissue. Thirteen undifferentiated bladder tumours and 10 undifferentiated prostatic carcinomas were incubated with E48 and prostate specific antigen. RESULTS: Reactivity to E48 was found in all grade 1 and 2 carcinomas and most (83%) grade 3 tumours. At the ultrastructural level, expression was mainly associated with desmosomes and the cytoplasmic membrane. The reactivity of E48 was generally strong in fresh frozen tissue samples and remained preserved in fixed tissue samples. Ten of the 13 bladder carcinomas expressed E48; all prostatic tumours were totally negative. CONCLUSIONS: E48 is a sensitive marker for transitional cell carcinoma and suitable for differentiation between urothelial and prostatic undifferentiated carcinoma. It can be used in routinely processed, formalin fixed, biopsy specimens.     

Progress in radioimmunotherapy of head and neck-cancer (review)

There is an urgent need for an effective adjuvant systemic therapy for the treatment of patients with advanced head and neck cancer. This study shows that therapy based on the use of monoclonal antibodies (MAbs) is developing to a realistic option. A few years ago the first MAbs with specificity for squamous cell carcinoma of the head and neck (HNSCC) were produced, among which was MAb E48. In animal and patient studies, in which localization of radiolabelled MAb E48 was analysed qualitatively and quantitatively, it was demonstrated that a high percentage of the injected dose accumulated selectively in the tumour. These targeting properties, when exploited for delivery of toxic agents to the tumour, give MAb E48 potential for tumour therapy. Especially the application of MAb E48 in radioimmunotherapy (RIT) seems to be attractive due to the intrinsic radiosensitivity of HNSCC. Armed with 186-Rhenium, a radionuclide recently introduced in the field of RIT, MAb E48 IgG was shown to be highly capable of eradicating established HNSCC tumours in nude mice. Complete ablation of small HNSCC was observed in this animal model by a single bolus injection. In an effort to make MAb E48 less antigenic for human application a chimeric human/mouse MAb (cMAb) has been constructed by use of recombinant DNA techniques. This modification strongly improved the capacity of MAb E48 for mediating antibody-dependent cellular cytotoxicity (ADCC). When using this cMAb E48 for RIT of minimal residual disease it can be anticipated that ADCC activity may be supportive to irradiation, especially in the ablation of single disseminated cells or small cell aggregates. Extrapolating results obtained in nude mice to patients and taking into account the good targeting in patients, RIT with E48 IgG seems to have potential for the elimination of minimal residual disease. Based on this encouraging progress, preparations are being made to evaluate the efficacy of Re-186-labelled cMAb E48 as an adjuvant in a phase III study for the treatment of patients who are at high risk for developing distant metastases.     

MARS: a futile tool in centres without active liver transplant support.

BACKGROUND AND AIM: Studies on Molecular Adsorbent Recycling Systems (MARS) showed inconclusive survival benefits. PATIENTS AND METHOD: We evaluated the efficacy of MARS for patients with either acute liver failure (ALF) or acute-on-chronic liver failure (AoCLF) at our centre, from February 2002 till April 2006 retrospectively. RESULTS: Fifty ALF patients underwent median (range) three (1-10) sessions of MARS. Acute exacerbations of chronic hepatitis B (n=26) and drug-induced liver injury (n=12) were the commonest causes. Living donors were available in 6, 2 paediatric patients underwent left lobe and four adults underwent right lobe living donor liver transplant. Among the 44 ALF patients without a suitable living donor, one underwent deceased donor liver transplant and survived, another 19-year-old male with acute exacerbations of chronic hepatitis B recovered without transplant, and the rest died. Twenty-six had AoCLF and underwent four (1-10) MARS sessions. Sepsis (n=16) and upper gastrointestinal bleeding (n=4) were the commonest precipitating factors. None had a suitable living or deceased donor, suitable for transplantation during their hospitalization. Only one of 26 AoCLF patients survived the hospitalization, but the survivor died of sepsis 1 month later. CONCLUSION: In this non-randomized study, survival after MARS was related to the availability of transplant, and in patients where living or deceased donor transplant was unavailable, MARS was of little benefit. Randomized-controlled trials on MARS((R)) are urgently needed to clarify its clinical utility.     

Recurrent abdominal pain in children: a clinical approach

The term ‘recurrent abdominal pain’, or RAP, refers mainly to the duration of painful period and frequency of pain. The commonly accepted duration is at least three months in the preceding period, and over this three-month period, there are at least three episodes of pain that are severe enough to affect the daily activities of the affected patients. Over the years, with advances in medical technology and better understanding of the pathophysiology of abdominal pain, more and more organic causes have been identified. However, the most common cause of RAP in children is still functional in origin.     

Cerebral ischaemia in pituitary disorders—more common than previously thought: two case reports and literature review

Vasospasm and consequent cerebral ischaemia in aneurysmal subarachnoid haemorrhage are well-described. The development of cerebral ischaemia following pituitary tumour surgery is under-appreciated, and can be attributed to mainly cerebral vasospasm or internal carotid artery compression. We report on two patients with pituitary tumours who developed delayed cerebral ischaemia after transsphenoidal and transcranial pituitary macroadenoma decompression. The patients had vasospasm of intracranial vessels demonstrable on magnetic resonance angiogram. One recovered neurologically following nimodipine and hypertensive-hypervolaemia therapy while the other developed fulminant cerebral infarction. We discuss the complex multi-factorial mechanisms of cerebral ischaemia in pituitary disorders, as well as the management strategies and their limitations.     

Chronic diarrhoea in children: a clinical perspective.

Chronic diarrhoea in its previously described severe malnourished presentation is not common in Singapore. A retrospective study was made of children with chronic diarrhoea between January to September 1990, at the Department of Paediatrics, National University Hospital. Chronic diarrhoea in our context included all those who presented with diarrhoea of 7 or more days duration. The age range was one month to 11 years, with 23 males and 13 female patients. Approximately half of the patients had associated symptoms like fever. Anthropometric data of these patients revealed none less than the third percentile in height and weight. Clinically the patients were mainly well nourished, mildly dehydrated with no significant pallor or oedema. Perianal erythema though not excoriation was common being present in approximately 50%. Haematological parameters and electrolytes were generally normal. Mild elevation of urea and creatinine levels especially the former was present reflecting the relatively mild dehydration status. Infection was the main cause of the diarrhoea, 55% of stool cultures being positive mainly for Salmonella or rotavirus. Treatment was mainly directed at correcting dehydration. 40% needed antibiotics. Hence, chronic diarrhoea as seen in the National University Hospital is generally not debilitating. An infective cause must first be excluded with usage of antibiotics often necessary in young children.     

Abdominal coarctation and Alagille syndrome

Structural cardiac defects such as peripheral pulmonary stenosis are well-described in Alagille syndrome (AS), which is transmitted in an autosomal dominant inheritance. The genetic defect, with incomplete penetrance and variable expression, is localized to the short arm of chromosome 20. Abdominal coarctation is an uncommon congenital anomaly, with a spectrum of symptoms that may range from hypertension, intermittent claudication to abdominal pain. The association of abdominal coarctation with AS is rarely described. We report such a patient who also had aberrations of the visceral vascular supply involving the celiac, splenic, and superior mesenteric arteries. The indications to treat the coarctation, and in the context of a patient with AS, in whom liver transplantation may be contemplated at some stage, merit discussion.