Multiple primary cancer: an increasing health problem. Strategies for prevention in cancer survivors

This study was set to look for associations between the sites of the first and subsequent tumours in patients with multiple primary cancer (MPC) diagnosed from 1975 to 2002 in the reference hospital of a Spanish northern region, and propose prevention strategies. Patient and tumour variables were measured. Crude and standardized incidence rates per 100 000 inhabitants were obtained, and the association between MPC incidence and time was analysed by means of lineal regression. Relative risks were calculated to analyse associations between tumour sites. A total of 2737 MPC cases were registered (male/female ratio = 2). The percentage of MPC with respect to the total cancer increased from 1.78% in the 1975–1979 period to 7.08% in the 2000–2002 period ( R ² = 0.92; P  = 0.003). Great increase of incidence by time was found ( R ² = 0.90; P  = 0.004). Breast, prostate and bladder cancers increase risk of second tumour in female genital organs [RR 4.78 (3.84–5.93)], urinary system [RR 3.69 (2.89–4.69)] and male genital organs [RR 3.76 (2.84–4.69)] respectively. The MPC incidence is increasing. Interventions for MPC prevention, according to the European Code against Cancer, should be implemented early after the first cancer principally if patients suffer breast, bladder, prostate, larynx and colon cancers.     

Recombinant human granulocyte macrophage colony stimulating factor following alternating non cross resistant chemotherapy in Hodgkin's disease.

Fourteen patients with Hodgkin's disease (two previously untreated, 12 following relapse or with refractory disease) were treated with a combination chemotherapy regimen comprising chlorambucil, vinblastine, procarbazine, prednisolone, etoposide, vincristine and adriamycin administered on days 1-8. Recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) (mammalian glycosylated, Sandoz/Schering-Plough) was administered after alternate cycles of chemotherapy from day 10 for 7 days by continuous intravenous (i.v.) infusion in 12 patients in a dose finding study (dose: 2 micrograms/kg/day in four patients, 4 micrograms/kg/day in four patients and 8 micrograms/kg/day in four patients) and by daily subcutaneous (s/c) injections in two patients (8 micrograms/kg/day). There was a rapid peripheral leucocytosis following the rhGM-CSF, reaching a peak at 1-2 days in 12/14 patients. The initial leucocytosis was composed of neutrophils followed by a rise in immature myeloid cells. There was no difference observed in the duration or depth of the nadir following chemotherapy or in the rate of recovery of peripheral white cell counts between cycles with and without rhGM-CSF in patients treated with 2 and 4 micrograms/kg/day. At the dose of 8 micrograms/kg/day, 3/6 patients had a shorter nadir duration in the cycle with rhGM-CSF, compared with cycle without rhGM-CSF. There was no difference in frequency of infection in cycles with and without rhGM-CSF. Following chemotherapy, six patients achieved clinical remission, six partial remission and two had progressive disease.     

Acute myeloid leukemia in elderly adults.

One hundred and fifteen previously untreated adults aged over 60 years were referred to St Bartholomew's Hospital between 1978 and 1986 for management of acute myeloid leukemia (AML). Twenty-seven patients received symptomatic or palliative treatment only because combination chemotherapy was considered inappropriate. Eighty-eight patients received intensive chemotherapy with curative intent. There was a 48 per cent 'early death' rate and a 24 per cent incidence of resistant disease; complete remission (CR) was achieved in 25/88 patients (28 per cent). By multivariate analysis, a blast count less than 50 x 10(9)/l at presentation was the only factor predictive for achievement of CR whilst the latter and a presentation blast count less than 50 x 10(9)/l predicted for superior survival. Treatment was often curtailed on account of unacceptable toxicity; only 2/88 patients received the planned six cycles of treatment. Two patients died in CR. Four patients are alive in first CR at 3-9 years from treatment; one is alive in second CR following meningeal relapse. Overall survival was significantly worse than that of a contemporaneous group of adults aged 15-59 years treated at this hospital, but duration of CR was comparable. There are great difficulties involved in the intensive treatment of AML in elderly adults, but the major survival benefit gained by achieving CR should stimulate the search for better tolerated but still curative regimens.     

Relative Importance of Immune and Non-Immune Causes of Platelet Refractoriness

In this prospective study, 26 consecutive patients being treated for haematological malignancies receiving standard (i.e. non-leucocyte-depleted) blood components were observed for the development of refractoriness to platelet transfusions. One hundred and sixteen of the 266 (44%) platelet transfusions failed to produce a satisfactory response. In 102/116 (88%), the poor response was in the presence of non-immune factors known to be associated with platelet refractoriness. Non-immune factors were present alone in 78/116 (67%), and in combination with immune factors in a further 24/116 (21%). Immune factors (HLA and platelet-specific antibodies) were present during 29/116 (25%) of unsuccessful platelet transfusions. Statistical analysis confirmed that platelet refractoriness was significantly associated with the presence of nonimmune factors. The non-immune factors associated with refractoriness were often multiple, most frequently a combination of fever, infection and antibiotic therapy. This study provides evidence that immune mechanisms were not the predominant cause of platelet refractoriness in the patient population studied. It also suggests that measures for the prevention of HLA alloimmunisation, such as leucocyte depletion, may have a limited impact in reducing the incidence of refractoriness to platelet transfusions.     

Fibrinogen biosynthesis in isolated guinea pig megakaryocytes

Fibrinogen synthesis was investigated in guinea pig megakaryocytes. Purified megakaryocytes were incubated with 35S-methionine in methionine-free incubation medium for 18 hours. Newly synthesized fibrinogen in megakaryocyte lysates enriched with purified carrier guinea pig fibrinogen was immunoprecipitated with a specific anti- guinea pig fibrinogen antiserum produced in rabbits. Proteins in the immunoprecipitates were analyzed with a 3.5% to 10.0% gradient polyacrylamide slab gel electrophoresis and auto-radiography. Radioactivity was detected in a protein band of 340,000 daltons. In order to verify fibrinogen synthesis, immunoprecipitate was analyzed by two-dimensional slab gel electrophoresis: (1) the first dimension separated unreduced fibrinogen using a 3.5% to 10.0% gradient gel; (2) following reduction by 2-beta-mercaptoethanol, fibrinogen chains were separated in the second dimension using a 10% gel. Alpha, beta, and gamma fibrinogen chains, which represented carrier guinea pig plasma fibrinogen, were visualized by Coomassie brilliant blue. Autoradiography identified the incorporation of radioactivity into the three fibrinogen chains. In control experiments, immunoprecipitates, produced by exposing megakaryocyte lysates to preimmune rabbit serum and goat anti-rabbit IgG, were also analyzed by the two-dimensional gel system. Radioactivity was not detected in sites corresponding to the migration of fibrinogen subunits. The study demonstrates that isolated guinea pig megakaryocytes can synthesize fibrinogen. The electrophoretic mobility of newly synthesized fibrinogen and subunits is similar to that of guinea pig plasma fibrinogen.     

Long-term outcome of patients surviving for more than ten years following treatment for acute leukaemia

Between 1972 and 1988, 832 consecutive patients were treated for acute leukaemia at St. Bartholomew's Hospital; a retrospective analysis has been conducted to determine the clinical course and outcome for 101 who have survived > or = 10 years following treatment. At a median follow-up of 16 years (range 10-28 years), 86 patients (86 out of 834 total, 11%) were still alive. Long-term follow-up of patients who have survived > or = 10 years following treatment for acute leukaemia revealed that most patients were in normal health, although a significant number of complications had occurred.     

新疆铁路工人1001名体质状态相关分析

目的:调查新疆铁路工人的体质状况,并分析体质量指数和血糖、血脂及肝胆疾病之间的关系。方法:调查于2006-02/03进行。选择新疆乌鲁木齐铁路局公务段(盐湖-乌西)铁路职工1001人,测量其身高、体质量,计算体质量指数(<18.5kg/m2为体质量过低,18.5～24.9kg/m2为正常,25.0～29.9kg/m2为超重,>30kg/m2为肥胖);检测血脂(总胆固醇≥5.7mmol/L为高胆固醇血症;三酰甘油≥1.7mmol/L为高三酰甘油血症)、空腹血糖(≥7mmol/L为高血糖);B超观察肝、胆、脾、肾等器官。结果:受试者1001人全部进入结果分析。①体质量指数、三酰甘油、胆固醇、血糖值男女间未见差异。②体型正常者598人(59.74%),超重和肥胖者385人(38.46%)。③高三酰甘油症检出率:肥胖组明显高于体质量过低和正常组(58.33%,23.08%,7.32%,P<0.01);女性明显高于男性(23.95%,3.41%);体型正常者中女性明显高于男性(25.63%,0.68%)。④高胆固醇症、高血糖检出率男女比较差异不显著(P>0.05);超重者中女性高血糖检出率高于男性(10.14%,3.61%,P<0.05)。⑤脂肪肝检出率肥胖者最高为53.84%,体质量过低者最低5.56%;男性脂肪肝检出率高于女性(22.28%,16.81%,P<0.05);胆囊炎、胆结石检出率男女比较差异不显著。结论:①1001名铁路工人中体型异常者占40.36%,其中超重和肥胖者占38.66%。②随体质量指数增加,脂肪肝、高血脂检出率明显增加。     

Abnormalities of chromosome 16q in myeloid malignancy: 14 new cases and a review of the literature.

Fourteen patients with abnormalities of chromosome 16q, 13 with acute myelogenous leukaemia (AML), and one with refractory anaemia with excess of blasts (RAEB), are described. Seven patients had inv(16)(p13q22), two had del(16)(q22), and five had other abnormalities of 16q. Six of the seven patients with inv(16) had AML M4Eo and, following treatment with adriamycin, cytosine arabinoside, and 6-thioguanine, all achieved complete remission (CR). Neither patient with del(16)(q22) had typical M4Eo morphology at diagnosis; CR was achieved in one and one had resistant leukaemia. Patients with other abnormalities of 16q had blasts of diverse morphology and, although morphologically abnormal eosinophils were seen in three patients, this was not as marked as in the patients with inv(16). CR was achieved in two of the four patients with other abnormalities of 16q but duration of remission was short in both cases. These results suggest that most patients with del(16)(q22) and other abnormalities of 16q22 do not have typical AML M4Eo. Such patients tend to have a worse prognosis, and are more likely to have complex karyotypes typical of secondary leukaemia.     

Myeloma during a decade: Clinical experience in a single centre

One hundred and fifty-six patients with multiple myeloma weretreated over a period of 12 years at St. Bartholomew's Hospital.The progress of the disease was affected in 96/156 patients(61%). Response was defined as achieving a plateau of M component.A partial or complete response was seen in 68/120 patients treatedconventionally (56.5%), and in 28/36 patients treated with high-dosetherapy (77.7%). The median survival of the group as a wholewas 20 months, with a 2-year survival of just over 40%. In the36 patients treated with high-dose therapy, median survivalwas 6 years, and in a small group who have had maintenance Interferontherapy, the median has not yet been reached. In a univariateanalysis, age, intensity of therapy, haemoglobin and creatininelevels were significant, but multivariate analysis showed thatonly age and intensity of therapy were independent predictorsfor survival. The outlook for relapsed patients who showed progressionof disease remains poor, but palliation was best achieved bysteroid and Interferon in combination. Patients who achievecomplete responses and are maintained on Interferon appear tobe doing better both in terms of freedom from symptoms and insurvival, and methods to enable an elderly population to toleratethis form of therapy need to be explored. intensive chemotherapy, maintenance and relapse therapy, myeloma, survival