Primary retroperitoneal myxoid/round cell liposarcoma is a nonexisting disease: an immunohistochemical and molecular biological analysis

Almost all primary retroperitoneal liposarcomas can be classified as well-/dedifferentiated liposarcoma. Rarely, however, primary retroperitoneal liposarcoma is classified as myxoid/round cell liposarcoma, based on the presence of myxoid areas and vascular crow's feet pattern, which has resulted in a debate on the classification of liposarcoma in the retroperitoneum. Genetically, myxoid/round cell liposarcoma and well-/dedifferentiated liposarcoma are different diseases. Myxoid/round cell liposarcoma is characterized by a translocation causing FUS-CHOP or EWSR1-CHOP fusion, whereas well-/dedifferentiated liposarcoma is characterized by an amplification of the 12q13-15 region, including MDM2 and CDK4 genes. As myxoid/round cell liposarcoma is highly radio- and chemosensitive, differentiation between subtypes is important to optimize treatment. We studied whether primary retroperitoneal liposarcomas diagnosed as myxoid/round cell liposarcoma represent molecularly true myxoid/round cell liposarcoma or are histopathological mimics and represent well-/dedifferentiated liposarcoma. Primary retroperitoneal myxoid/round cell liposarcoma (n=16) were compared to primary extremity myxoid/round cell liposarcoma (n=20). Histopathological and immunohistochemical features were studied. Amplification status of the 12q13-15 region was studied using a multiplex ligation-dependent probe amplification analysis, and FUS-CHOP or EWS-CHOP translocations were studied using RT-PCR. In primary retroperitoneal myxoid/round cell liposarcoma, MDM2 and CDK4 staining was both positive in 12 of 15 cases. In primary extremity myxoid/round cell liposarcoma, MDM2 was negative in 18/20 and CDK4 was negative in all cases. Multiplex ligation-dependent probe amplification showed the amplification of 12q13-15 region in 16/16 primary retroperitoneal myxoid/round cell liposarcomas and in 1/20 primary extremity myxoid/round cell liposarcomas. Translocation was present in all (18/18) primary extremity myxoid/round cell liposarcomas, but absent in all primary retroperitoneal myxoid/round cell liposarcomas. On the basis of immunohistochemical and molecular characteristics, apparent primary retroperitoneal myxoid/round cell liposarcoma can be recognized as well-/dedifferentiated liposarcoma with morphological features mimicking myxoid/round cell liposarcoma. In these cases, treatment should probably be specifically designed as for well-/dedifferentiated liposarcoma. Moreover, finding of myxoid/round cell liposarcoma translocations in a retroperitoneal localization is highly suggestive of metastasis and should prompt search for a primary localization outside the retroperitoneum.     

Causes of death after therapy for early stage Hodgkin's disease entered on EORTC protocols. EORTC Lymphoma Cooperative Group

The risk of dying from different causes after Hodgkin's disease (HD) therapy has been quantified from a series of 1,449 patients with early stages included in four successive clinical trials conducted by the European Organization for Research and Treatment of Cancer (EORTC) Lymphoma Cooperative Group since 1963. Overall, 240 patients died and the 15-year survival rate was 69% whereas the expected rate was 95%. The standardized mortality ratio (SMR) technique was used to quantify excess deaths as a function of time since first therapy. At each interval, SMR was significantly increased, giving: 0-3 year, 8.86 (p less than 0.001); 4-6 year, 9.25 (p less than 0.001); 7-9 year, 7.08 (p less than 0.001); 10-12 year, 9.53 (p less than 0.001); 13-15 year, 4.37 (p less than 0.01); and 16+ years, 3.80 (p less than 0.05). While the proportion of deaths as a consequence of HD progression, treatment side-effect, and intercurrent disease decreased with time, that of second cancer and cardiac failure peaked during the 10-12 year post-treatment interval. After 15 years of follow-up, the risk of dying from causes other than HD continued to increase. These findings indicate that although probably cured from HD, patients are at higher risk for death than expected, a risk that might be a consequence of therapy.     

Advanced small cell carcinoma of the bladder. Successful treatment with combined radical cystoprostatectomy and adjuvant methotrexate, vinblastine, doxorubicin, and cisplatin chemotherapy

Undifferentiated small cell carcinoma of the bladder is a rare tumor with pathologic features similar to those of oat cell carcinoma of the lung. This neuroendocrine neoplasm of the bladder has a highly malignant biological behavior; most patients present with either locally advanced or distant metastatic disease and die despite aggressive therapy. Here the histologic, immunocytochemical, and ultrastructural features of small cell carcinoma of the bladder are reviewed in detail. In addition, two patients with advanced small cell carcinoma of the bladder who were treated successfully with radical cystoprostatectomy and adjuvant methotrexate, vinblastine, doxorubicin, and cisplatin chemotherapy (M-VAC) are presented. Both men had regional lymph node involvement and are disease free at follow-up of 1 year and 2.5 years, respectively. This is the first report of combined surgical and M-VAC chemotherapy in the treatment of undifferentiated small cell carcinoma of the bladder.     

Femoral capital osteonecrosis: MR finding of diffuse marrow abnormalities without focal lesions

Six painful hips in five patients were examined with magnetic resonance (MR) imaging and were found to have diffuse signal abnormalities in the marrow of the femoral head and neck, which extended into the intertrochanteric area in five cases. The abnormal regions were low in signal intensity on images obtained with a short repetition time (TR) and a short echo time (TE) and were isointense or hyperintense on long TR/TE images--findings that have been attributed by others to bone marrow edema. Edema was also seen in marrow just above the acetabulum in two cases. No focal abnormalities characteristic of osteonecrosis were seen. Osteonecrosis was subsequently shown to be present in all six femoral heads at core biopsy (three cases) or by subsequent development of focal MR abnormalities reported to be highly specific for osteonecrosis (three cases). The affected hips had been radiographically normal or subtly osteopenic and had shown intense radionuclide uptake in the femoral head at scintigraphy, with lesser abnormality in the neck and intertrochanteric region. Follow-up MR examinations of five of the six femoral heads showed the diffuse abnormalities to have been transient. Although diffuse MR abnormalities in the proximal femur are not specific, they may indicate the presence of osteonecrosis of the femoral head.     

Iron, ascorbate and copper status of Sowetan Blacks with calcific chronic pancreatitis

Vitamin C can be used to overcome oxidative stress and ease pain in chronic pancreatitis. But its use is deprecated in conditions of tissue iron overload, because its bioactive form, ascorbate, can accelerate free-radical reactions that are driven by transition metals. We measured iron, ascorbate and copper in Sowetan Blacks (RSA) with chronic pancreatitis, obtaining serum/plasma from 14 consecutive patients and 15 controls. Compared with data from corresponding groups in Manchester, African samples had less ascorbate (p < 0.0001), but more caeruloplasmin (p < 0.0001). African and British controls had comparable iron and iron-binding capacity. Plasma from African patients had less ascorbate than that from African controls (p < 0.005) and in six samples, ferritin exceeded 300 micrograms/l (677 pmol/l). Low- molecular-mass iron or copper, capable of participating in free radical reactions, was not detected. British patients, had similar caeruloplasmin levels to African patients but higher ascorbate levels. There is no evidence of iron overload in our African samples. Outwardly healthy controls from Soweto have elevated levels of caeruloplasmin, possibly to compensate for dietary deficiency of ascorbate. Persistent oxidative stress is a unifying feature of chronic pancreatitis, but its degree is higher in African than British patients. Supplements of vitamin C should be safe in Blacks of southern Africa.      

自体造血干细胞的体外净化

目的:综合分析自体造血干细胞体外净化的方法。资料来源:应用计算机检索Medline 1991-01/2003-12有关自体造血干细胞体外净化方法的文章,检索词“purging,HSCT”,并限定文章语言种类为English。同时计算机检索CNKI数据库1991-01/2003-12有关自体造血干细胞体外净化方法的文章,检索词“体外净化,PUVA”,并限定文章语言种类为中文。资料选择:对相关资料进行整理,选取同一领域、不同方面的文献,以近期发表或权威杂志的文章优先。资料提炼:共检索到42篇有关自体造血干细胞体外净化方法的文献,其中24篇文章符合要求。排除18篇,其中15篇系重复同一研究,3篇为Meta分析。资料综合:自体造血干细胞的体外净化方法很多,如物理方法、生物学方法、药物方法、免疫净化、基因净化等。每种净化方法都有其各自的优势和不足,如淋巴系统疾病可以采用免疫净化;慢性粒细胞白血病患者可考虑反义技术;大多数患者则均可以考虑药物净化的方法。结论:针对不同的疾病,可以选择不同的净化方法,还可以将几种净化方法联合起来,其效果和方法的改进也在不断的研究探索中。     

Reduction in transmission of hepatitis C after the introduction of a heat-treatment step in the production of C1-inhibitor concentrate

BACKGROUND: The transmission of viral infections via protein concentrates made from a large pool of plasma depends on the selection of donors, fractionation process, and virucidal methods. To date, no data are available on the infectivity risk of plasma concentrates of the inhibitor of the first component of complement (C1-INH). STUDY DESIGN AND METHODS: The prevalence of blood-borne viral infections and levels of transaminases were evaluated in patients treated with a large- pool plasma concentrate of the inhibitor of C1-INH before and after the introduction of virucidal methods. The study included 85 patients with hereditary angioedema and 4 with acquired angioedema. The patients were divided into three groups: 1) 48 untreated patients; 2) 22 patients treated with non-virus-inactivated C1-INH concentrates; and 3) 19 patients treated with virus-inactivated concentrates. Serum samples obtained at various times after the infusion of concentrate were assayed for alanine amino-transferase and tested for hepatitis B surface antigen and antibodies to hepatitis C virus (anti-HCV) and human immunodeficiency virus (anti-HIV); anti-HCV-negative subjects exposed to the concentrate were also tested for HCV RNA. RESULTS: Prevalences of HCV infection and elevated alanine aminotransferase are significantly lower in patients treated with virus-inactivated concentrates than in those exposed to non-virus-inactivated concentrates. No patients were anti-HIV positive. CONCLUSION: This study suggests that C1-INH concentrates transmitted HCV, but that the virucidal methods adopted are effective in reducing the infectivity.     

Serial immunoreactive erythropoietin levels in autologous blood donors

The variations in plasma erythropoietin (EPO) concentration during preoperative deposit of autologous blood were studied in 12 patients (8 men, 4 women). Four donations were scheduled at weekly intervals. A predonation hemoglobin concentration of 11 g per dL (110 g/L) was required. Hemoglobin concentration decreased from 14.3 +/- 1.1 g per dL (143 +/- 11 g/L) (mean +/- SD) before the first donation to 11.7 +/- 0.7 g per dL (117 +/- 7 g/L) on Day 22 (p less than or equal to 0.0001). Reticulocyte counts increased from a median of 31,800 (range, 4900-95,000) per microL (median, 32 x 10(9)/L [range, 5-95 x 10(9)/L]) to 93,800 (16,800-194,900) per microL (median, 94 x 10(9)/L [range, 17-195 x 10(9)/L]) on Day 28 (p less than or equal to 0.01). Plasma EPO concentration was 17.8 +/- 5.1 mU per mL prior to the first donation and displayed a small and transient peak after each donation. A sustained elevation followed each peak. Although plasma EPO concentration differed significantly from the baseline value after the first donation, only the peak concentrations after the second (35.5 +/- 15.5 mU/mL), third (38.0 +/- 14.5 mU/mL), and fourth (36.1 +/- 11.0 mU/mL) donations exceeded the normal range. The moderate, biphasic increase in plasma EPO concentration and the moderate increase in erythropoiesis suggest two strategies in autologous blood donation that should be investigated with respect to efficiency and safety: 1) more aggressive donation schemes, which reduce donation intervals and/or the minimum hemoglobin concentration and 2) the administration of recombinant human EPO.     

Transmission of hepatitis G virus in patients with angioedema treated with steam-heated plasma concentrates of C1 inhibitor

BACKGROUND: Hepatitis G virus (HGV) is a blood-borne flavivirus that may cause acute and chronic transfusion-transmitted infections. Patients with complement component 1 (C1) inhibitor (C1-INH) deficiency may acquire blood-borne infections through infusion of plasma concentrates. STUDY DESIGN AND METHODS: Serum samples from 84 patients with C1-INH deficiency (19 who received unmodified C1-INH concentrates, 23 who received steam-heated concentrates, and 42 untreated patients) were tested for HGV RNA and hepatitis C virus (HCV) RNA by a nested polymerase chain reaction (PCR). The samples were also tested for antibodies to the E2 envelope protein of HGV (anti-HGV) and to HCV with enzyme-linked immunosorbent assays. RESULTS: Nine (11%) patients had serum HGV RNA; that is, 7 (17%) of 42 patients previously treated with C1-INH concentrates and 2 of 42 previously untreated patients. HGV RNA was as common in the 19 patients treated with unmodified concentrates as in the 23 given steam-heated concentrates (16 vs. 17%, p = 0.60). Anti-HGV was more common among the recipients of unmodified concentrates than among those given steam-heated concentrates (26 vs. 0%, p = 0.014). HCV RNA was more frequently detected in treated patients than in untreated patients (33 vs. 7%, p = 0.005) and in the 19 recipients of unmodified concentrates than in the 23 treated with steam-heated concentrates (58 vs. 16%, p = 0.003). Only one HGV RNA- seropositive patient had elevated serum aminotransferase activity, compared to 11 with HCV RNA. CONCLUSION: HGV was transmitted by both unmodified and steam-heated concentrates, but it caused persistent viremia in a minority of the cases and was rarely associated with liver disease.