Characteristics and prognosis of KI-1 positive anaplastic large cell lymphoma in Asians.

BACKGROUND: Ki-1 positive anaplastic large cell lymphoma is a rare type of non-Hodgkin's lymphoma (NHL), and has not been extensively described in Asian patients. AIM: To evaluate the clinical characteristics, prognostic factors and treatment outcome of Ki-1 positive lymphoma in an Asian community. METHODS: A retrospective analysis of all patients with CD30 antigen positive anaplastic large cell lymphoma from 1987 to 1996 in a single institution. RESULTS: Of 218 patients with NHL, ten (5%) were identified with Ki-1 positive anaplastic large cell lymphoma. Eight were Chinese, two Indians. The male:female ratio was 1.5:1, and the median age was 32 years. Seven patients presented with B-symptoms, and five had stage III/IV disease. The majority (seven of ten) was low- or low-intermediate risk according to the International Prognostic Index (IPI). Four out of five cases immunophenotyped showed a T-cell origin. Five out of eight patients who received first-line combination chemotherapy achieved a complete remission. Two relapsed, with one being re-induced into a durable second remission. One patient with recurrent cutaneous lymphoma received solely radiotherapy and was disease-free at 20+ years from diagnosis. At analysis, two patients had died, five were disease-free at four, 27, 78, 89 months and 20 years respectively, and three were alive with disease. The IPI appears to have prognostic significance. CONCLUSION: Incidence and clinical characteristics in our Asian patients were similar to those described in Western populations. The IPI appears to have prognostic relevance. In approximately one-third of patients, long term survival can be achieved with standard treatment.

Treatment of acute promyelocytic leukaemia in first relapse with all-trans retinoic acid.

A 27-year-old Chinese woman with acute promyelocytic leukaemia in first relapse after the initial conventional induction chemotherapy 18 months earlier was treated with all-trans retinoic acid (ATRA) at an initial dose of 45 mg/m2 and subsequently increased to 65 mg/m2 on day 15. Complete remission was achieved after a total of 40 days of ATRA alone. Serial marrow examinations during induction showed progressive maturation of myelopoiesis without bone marrow hypoplasia. There was a significant reduction in number of cells with the t(15;17) translocation when complete remission was achieved. ATRA was very well-tolerated. The symptoms of dry skin and intermittent headache were self-limiting.

Multiple myeloma: the National University Hospital (NUH) experience.

The aim of this retrospective study was to define the characteristics of local patients with multiple myeloma. Twenty-nine de novo cases were accrued from October 1986 to January 1992 at the National University Hospital of Singapore. Features like median age of presentation, sex distribution, the incidence of IgG, IgA and light chain subtypes were similar to published data. However IgD myeloma appeared to be more common here and it tended to be more advanced at presentation. Objective response rate to treatment with the melphalan-prednisolone combination was about 40% with a median survival of 18 months.

Acute deep vein thrombosis in hospital practice.

A recent cross sectional study on symptomatic acute deep vein thrombosis at the National University Hospital (NUH) in Singapore found a frequency rate of 0.79 per 1000 patient admissions. A total of 39 patients were accrued over 18 months, 36 with deep vein thrombosis alone and three complicated by pulmonary embolism. No sex or ethnic predilection was observed in this cohort of hospitalised patients. Twenty-eight (71.8%) patients were 40 years or older. Majority (89.7%) of patients had at least two predisposing factors. While prolonged bedrest and operative procedures featured equally frequently in patients above and below 40 years, neoplasms were predominantly associated with the former and protein C or S deficiency primarily with the latter. The exhaustive laboratory confirmation of an inherent thrombotic tendency is recommended only for patients below 40 years of age.

Cisplatin and 5-fluorouracil continuous infusion for metastatic nasopharyngeal carcinoma.

The activity of cisplatin and a 120-hour continuous infusion of 5-fluorouracil (5-FU) was evaluated in 25 patients with metastatic nasopharyngeal carcinoma. Cisplatin 100 mg/m2 and 5-FU 1000 mg/m2/day by continuous infusion for 120 hours were given via an implanted venous access device and ambulatory infusion pump. Eighteen (72%) patients had multiple sites of metastases and seven (28%) patients had only bony metastases. Subjective responses in terms of pain relief and improvement in performance status were seen in 21 (84%) patients. Overall objective response was seen in 19 (76%) patients with two complete remissions (CR) and 17 partial remissions (PR). Locoregional disease responded more completely and rapidly than bony or visceral metastases. Toxicities included nausea, vomiting, neuropathy and one septic death. Cisplatin and 5-FU by continuous infusion represent an effective treatment for metastatic nasopharyngeal carcinoma.

Prognostic usefulness of cytogenetic analysis for haematological malignancies--two case reports on acute myeloid leukaemia.

Since the setup of marrow cytogenetic analysis at the National University Hospital (NUH) of Singapore in 1988, we have systematically examined all patients with haematological neoplasia for clonal abnormalities. In most patients, diagnosis was unequivocal on clinical and morphological grounds so that karyotyping was undertaken for prognostic purposes. Two patients are described who illustrate the prognostic implications of nonrandom chromosomal derangements. They highlight the increasing appreciation of the importance of cytogenetic analysis as an independent and reliable prognostic tool in the management of haematological malignancies.

Hepatocellular carcinoma--a case series of 104 patients.

The records of one hundred and four patients with confirmed hepatocellular carcinoma seen over a two year period at the National University Hospital were analysed to elucidate the clinical features of our local patients and to assess their response to various therapeutic modalities. Chinese males were over-represented with a peak frequency in the sixth to eighth decade of life. Seventy-five percent of the patients were HBsAg positive and at least 88% had evidence of previous Hepatitis B infection. Ninety-one percent were symptomatic at presentation with pain being the most common symptom. Hepatomegaly with features of cirrhosis were the main physical findings. Seventy percent of the patients presented within three months after the onset of symptoms. The majority of patients had stage II or III disease at diagnosis. Twenty percent of patients had normal alpha-fetoprotein levels. Chemotherapy did not appear to show a survival benefit. Curative surgical resection was feasible in about 10% of patients and it remains the only chance for long term survival. There is an urgent need to identify more effective drugs or other modalities to treat this common and rapidly fatal malignancy. Identification of high risk patients should prompt screening with both serum alpha-fetoprotein and ultrasonography of the liver.

Malignant glandular triton tumor.

A case of left brachial plexus-related malignant peripheral nerve sheath tumor showing neoplastic, glandular, and rhabdomyoblastic elements in a 39-year-old Chinese man is reported. The authors suggested that this tumor be termed a malignant glandular triton tumor in view of the presence of the adenocarcinomatous component. The patient had extensive local recurrence comprising mainly the Schwann spindle cells within a year after complete piecemeal removal and died 15 months later after the initial presentation. The natural behavior of this tumor, as in other reported cases of malignant triton tumor, is extremely aggressive, unlike malignant schwannoma or glandular malignant schwannoma. The histogenesis of this tumor is likely to be from primitive neural crest cells, Schwann's cell precursors, or metaplastic malignant Schwann's cells.

Cytogenetic analysis in myeloid malignancies.

Forty-one patients with myeloid malignancies, majority newly diagnosed and previously untreated, were systematically karyotyped between January 1988 and December 1989 using fluorodeoxyuridine (FdU) synchronisation and Giemsa banding techniques. Eighteen patients had acute myeloid leukaemia (AML), 13 had one form or other of a myeloproliferative disorder and 10 fulfilled the clinical and morphological criteria for the myelodysplastic syndrome (MDS). Ten AML patients had cytogenetic abnormalities. All 6 chronic myeloid leukaemia (CML) patients carried the Philadelphia chromosome with 2 having additional abnormal clones. Only four MDS patients showed involvement of either chromosome 5 or 7.

Treatment of adrenal cortical carcinoma with mitotane: outcome and complications.

Adrenal cortical carcinoma is a rare tumour with a poor prognosis. We report a patient with metastatic adrenal cortical carcinoma who responded dramatically to Mitotane (o,p'-DDD). Unlike previous reports of metastatic adrenal cortical carcinoma in which complete remission was obtained with high dose Mitotane treatment, the dose of Mitotane used in this patient was low. However, she developed unusual side-effects such as hyperpigmentation, low plasma cortisol and high adrenocorticotropic (ACTH) levels. The side effects closely resemble those in Nelson's syndrome and were reversed by cortisone replacement. The mechanism of actions of Mitotane is discussed with emphasis on its effect on corticosteroid metabolism.

Chemotherapy of adult acute myeloid leukaemia.

Great strides have been made in the chemotherapy of adult acute myeloid leukaemia in the last two decades. This paper describes our experience in the treatment of adult acute myeloid leukaemia from 1980-88. About two thirds of patients achieve remission with a standard chemotherapy protocol. Early disease relapse and measures to prevent it are major problems. The majority of patients with adult myeloid leukaemia, presently, are not cured with chemotherapy alone.

Extensive bone marrow necrosis in cancer.

Extensive bone marrow necrosis is an uncommon finding in patients with cancer. This paper presents the clinical details of two patients in whom this condition was the presenting feature. The diagnostic criteria, pathogenesis and prognosis of this poorly understood problem are then discussed. Although prognosis is usually grave, prompt recognition and proper management of this condition may result in remission of the disease and regeneration of the marrow.

Non-surgical management of liver metastases.

The liver represents the most common site of visceral metastasis for primary gastrointestinal neoplasms, but it is also a common site of metastasis for extra-abdominal tumours including breast cancer, lung cancer as well as other cancers. Metastatic liver disease is often the cause of death for cancer patients. Metastatic liver disease is a heterogenous entity depending upon histologic type, site of primary tumour and other extrahepatic involvement. Surgical resection is feasible only in highly selected patients with no extrahepatic metastasis. The nonsurgical modalities of management of liver metastases include radiotherapy, chemotherapy, biologicals or a combination of these modalities. Hepatic irradiation can produce satisfactory palliation but has dose limiting toxicity of radiation hepatitis. The systemic chemotherapy of liver metastases has evolved over the past decades from single agent systemic treatment to regional infusion chemotherapy. The drugs employed in treatment depend on the site of primary tumour. 5-fluorouracil remains the mainstay of chemotherapy in most gastrointestinal cancers. Recent technological advances in drug delivery system and genetic engineering have given new vistas to nonsurgical management of liver metastases. Ambulatory or implantable pumps have enabled drugs to be delivered by continuous infusion via an implantable vascular access system. Monoclonal antibodies conjugated to toxins or radioisotopes offer exciting prospects for targeted therapy.

Totally implantable central venous access for cancer patients in Singapore.

Sustained venous access is assuming increasing importance in clinical medical practice for the infusion of antibiotics, cytotoxic drugs, blood products and parenteral nutrition. The limitation of peripheral venous access in patients receiving cancer chemotherapy can be a major problem. Many antineoplastic drugs are vesicant and may cause chemical ulcers when infiltrated or phlebitis and thrombosis. Recent technological advances in development of non-thrombogenic silastic catheters have facilitated in-dwelling catheters to be implanted for long periods. Port-A-Cath is a totally implantable vascular access system which allows for blood to be sampled and also infusion of drugs and blood products. Between March 1985 to October 1987, 20 devices were implanted on 19 patients (14 males and 5 females). Criteria were drawn up to select these patients. The quality of life was significantly improved for these patients who receive long term chemotherapy or blood products through this device. There were 6 episodes of transitory occlusion of catheter and 1 episode of infection. Continuous infusion of drugs given through this device does not produce chemical phlebitis. It has also facilitated new methods of delivering cytotoxic drugs and analgesia.

4'-Epidoxorubicin (Epirubicin) as a single agent in advanced primary hepatocellular carcinoma--a preliminary experience.

41Epidoxorubicin (Epirubicin) is a new anthracycline analogue which has activity in a variety of cancers. Advanced primary hepatocellular carcinoma is a rapidly fatal neoplasm. Studies with doxorubicin (Adriamycin) in Africa and Asia have shown a response rate around 30-50% with modes gains in median survivals in patients who responded. We report here our preliminary experience with epirubicin in advanced primary hepatocellular carcinoma. We treated 13 patients with advanced primary hepatocellular carcinoma with epirubicin using a dose of schedule of 60 mg/m +/- at the beginning and gradually escalated to 90 mg/m +/- as tolerated. All patients had no prior chemotherapy. Median age was 51 years with range of 31 to 70 years. Cardiotoxicity was serially monitored with radionuclide multigated left ventriculogram. Objective responses were observed in 3 (23%) patients of the 13 evaluable patients. The median duration of these responders was 30 weeks (range 20 to 42). The overall median survival was 11 weeks. Two patients had cardiotoxicity as measured by a significant fall in left ventricular ejection fraction. The toxicities are much less than doxorubicin and better tolerated. We feel that epirubicin has definite activity in primary hepatocellular carcinoma even in patients with advanced disease.