Low incidence of secondary myelodysplasia and acute myeloid leukemia after high-dose chemotherapy as adjuvant therapy for breast cancer patients: a study by the Solid Tumors Working Party of the European Group for Blood and Marrow Transplantation.

BACKGROUND: To determine the incidence of secondary myelodysplasia (sMDS) or acute myeloid leukemia (AML) in node-positive breast cancer patients who received high-dose chemotherapy (HDCT) followed by autologous stem-cell support as adjuvant therapy. PATIENTS AND METHODS: The incidence of sMDS/AML was retrospectively assessed in 364 node-positive breast cancer patients who received HDCT followed by autologous stem-cell support as adjuvant therapy between November 1989 and December 1997 and were reported to the European Group for Blood and Marrow Transplantation registry. RESULTS: The median age of the patients was 45 years (range 22-62 years). Two hundred and ninety-one patients received peripheral blood stem cells and 55 patients received autologous bone marrow as stem-cell support. The most frequently used conditioning regimen was the STAMP-V regimen (32%), followed by melphalan-thiotepa (22%) and melphalan-mitoxantrone-cyclophosphamide (21%). The 5-year probability of overall survival is 71% (95% CI 65% to 77%). After a median follow-up of 48 months (range 1-108 months) only one case of AML was observed, resulting in a crude incidence of 0.27%. This case of AML was observed 18 months after HDCT consisting of three cycles of epirubicin and cyclophosphamide with a cumulative dose of epirubicin 960 mg and cyclophosphamide 19 g. The French-American-British type of AML was M4, and the cytogenetic analysis showed a translocation t(9;11)(p22;q23). After complete remission following high-dose cytarabine and idarubicin the patient relapsed and died. CONCLUSIONS: In contrast to patients with malignant lymphoma there seems to be no increased risk of sMDS/AML after HDCT in breast cancer. Continued monitoring is required to confirm this low incidence after a longer follow-up period.     

Hospital-related differences in breast cancer management

A retrospective review is presented of 1353 consecutivepatients with histopathologically confirmed invasive breast carcinoma treatedradically with curative intent during the decade 1980–89.None had received adjuvant systemic therapy with hormonesor prolonged chemotherapy. The distribution of lymph-node negative(N–) and lymph-node positive (N+) patients was 75%and 25%, respectively.The treatment and outcome were analysed as regardsconventional prognostic parameters, in particular considering the axillarylymph-node status and the responsible hospital category (GeneralMunicipal Hospitals (MH)) versus Comprehensive Cancer Center (CC)).The most striking difference was detected as regardsthe number of examined lymph nodes. The mediannumber of nodes described at the MH was7, as compared to 14 at the CC(p < 0.001). In patients with pT1 tumoursthe highest rate of lymph-node positivity was observedwhen 10 or more axillary nodes were removed.Adjuvant radiotherapy reduced the loco-regional recurrence rate inthe N– patients, whereas only the regional recurrenceswere reduced among the N+ patients. The five-and 10-year tumor-related survival rates were 86% and76%, respectively, with no difference between the MHand the CC.As life-prolonging adjuvant hormone therapy and chemotherapy isnow available for patients with axillary lymph nodemetastases, it is important that patients with breastcancer are operated adequately with the aim toremove at least 10 axillary lymph nodes. Athorough examination of the axillary content should beperformed by the pathologist, and the number ofresected lymph nodes and metastases should be reported.The establishment of nation-wide standard criteria for themanagement of breast cancer is recommended.     

An Analysis of Approaches to the Management of Endometrial Cancer in North America: A CTF Study

Objective.The aim of this study was to define the clinical–therapeutical approach to endometrial cancer now being followed in some of the most important centers of reference for gynecological cancer in North America by means of a questionnaire.Study design.The questionnaire focused on four principal areas: (1) surgical staging and therapy; (2) adjuvant treatment; (3) treatment modifications; and (4) management of advanced stages (FIGO III–IV).Results.There were 48 evaluable responses (77%) received by the end of December 1994 which were considered for this analysis. Lymphadenectomy is utilized routinely in 26/48 centers (54.2%) and in selective clinical–pathological conditions in another 21/48 centers (43.5%). In the majority of centers (31/48; 64.6%) radical surgery is utilized for selected indications such as cervical involvement. Only 3/48 (6.2%) centers consider the vaginal approach totally inappropriate. The great majority (40/48; 83.3%) of the centers considered postsurgical adjuvant therapy to be necessary in FIGO Stage Ic. Brachytherapy is routinely performed in 3 centers (6.2%) in postsurgical management of Stage I endometrial cancer, while the majority of the centers (31/48; 64.6%) perform brachytherapy of the vaginal vault in certain clinical–pathological conditions. A wide variety of treatments are used for advanced stages (FIGO III–IV).Conclusions.It emerges that some controversial aspects exist on endometrial cancer treatment, and these conflicting data need a large-scale multicenter randomized clinical trial.     

hCGβ-C3d3融合蛋白免疫BALB/c小鼠及其抗血清对hCG诱导鼠子宫增重的抑制效应

目的:通过分子佐剂C3d3增强hCGb避孕疫苗的免疫原性。方法:采用分子生物学技术以phCMV1为载体分别构建分泌型、带有6个组氨酸纯化标签的真核表达质粒phCMV1-6His-hCGb-C3d3和phCMV1-6His-hCGb,在CHO细胞中获得稳定、高效表达的重组蛋白,并用镍柱和凝胶过滤层析对其进行分离、纯化。分别用hCGb-C3d3融合蛋白和单用hCGb间隔4周两次免疫生育期雌性BALB/c小鼠,ELISA测定血清中抗hCGb抗体滴度,并对各组小鼠产生的抗血清拮抗hCG诱导的小鼠子宫增重效应进行比较。结果:C3d3使hCGb蛋白疫苗的免疫原性增强1 995倍,hCGb-C3d3融合蛋白免疫小鼠产生的抗血清具有很强的抑制小鼠子宫增重作用。结论:通过分子佐剂C3d3可以大幅提高机体对hCGb的体液免疫应答能力,hCGb-C3d3融合蛋白免疫小鼠产生的抗血清对hCG的生物学作用具有更强的抑制效应。     

晚期肾母细胞瘤的术前治疗

目的　探讨晚期肾母细胞瘤术前治疗的必要性 ,并分析术前全身化疗和肾动脉化疗栓塞合并全身化疗的治疗效果。方法　 30例Ⅲ、Ⅳ期肾母细胞瘤分为 2组 :①未术前治疗组 11例 ;②术前治疗组 19例 (又分为全身化疗亚组 6例和肾动脉化疗栓塞合并全身化疗亚组 13例 )。结果　未术前治疗组手术死亡率 18.2 % (2 /11) ,肿瘤完整切除率 9.1% (1/11) ,2年无瘤生存率 9.1% (1/11)。术前治疗组手术死亡率 0 % (0 /19) ,肿瘤完整切除率 6 3.2 % (12 /19) ,2年无瘤生存率 73.7% (14 /19)。肿瘤完整切除率比较和 2年无瘤生存率比较差异均有高度显著性意义 (<0 .0 1)。术前治疗组中 ,肾动脉化疗栓塞合并全身化疗亚组完整切除率和 2年无瘤生存率均高于全身化疗亚组。结论　术前治疗可明显提高Ⅲ、Ⅳ期肾母细胞瘤的完整切除率和 2年无瘤生存率。术前肾动脉化疗栓塞与全身用药化疗并用疗效更好。     

Whole-abdomen, single-dose consolidation radiotherapy in patients with pathologically confirmed complete remission of advanced ovarian epithelial carcinoma: a long-term survival analysis

The value of consolidation therapy in advanced epithelial ovarian carcinoma patients is controversial. The aim of the present study was to assess the long-term survival of patients with a pathologically confirmed complete remission who had consolidation by single-dose, whole-abdominopelvic radiotherapy. Of 96 histologically confirmed stage II-IV epithelial ovarian carcinoma patients who underwent cytoreductive surgery followed by high-dose, platin-based chemotherapy, 57 were in complete clinical remission at the end of therapy and 50 underwent a second-look laparotomy. The study group comprises 32 consecutive patients who had no pathological evidence of disease and who received 800 cGy single-dose, whole-abdominal radiotherapy by an 8 MEV linear accelerator in a single fraction. The absolute 5-year survival and the actuarial 10-year survival were 78.7 and 63.3%, respectively. The survival was significantly better in patients who had < or =2 cm residual disease at the completion of the original operation. No severe postradiation complications were encountered. Mild complications were seen in three (9.4%) patients. Our data indicate a favorable long-term survival of patients with a negative second-look laparotomy who had consolidation with single-dose, whole-abdominal radiotherapy. These results seem to suggest that a collaborative, prospective, randomized multiarm study is indicated to solve the controversial issue of consolidation therapy.     

种植体磁性固位全口义齿的初步研究

目的探讨种植体磁性附着体固位全口义齿的临床应用。方法下颌牙槽嵴严重萎缩吸收的全口义齿患者，在下颌骨前牙区骨内植入2枚种植体，4个月后制作覆盖全口义齿，磁铁安装在义齿面内。衔铁固定在种植体上，利用磁性附着体的磁吸力使全口义齿固位在牙槽骨上。结果种植体磁性固位全口义齿固位良好，患者说话和咀嚼效果满意。结论种植体磁性附体固位全口义齿。对于牙槽嵴严重萎缩吸收的患者，能明显示改善固位和咀嚼效果。     

英卡膦酸盐对佐剂关节炎模型大鼠骨与关节的影响

目的:研究英卡膦酸盐对佐剂关节炎大鼠的关节炎症、肿胀以及结构破坏的影响.方法:35只雌性Lewis大白鼠随机分为5组:正常对照组、模型组和英卡膦酸盐低、中、高剂量组,每组7只.除正常对照组外,其余4组接种佛氏完全佐剂诱发关节炎.英卡膦酸盐3个剂量组自接种之日起,连续42 d皮下注射英卡膦酸盐0.01,0.1和1 mg·kg-1·d-1,qd.记录关节炎分数,测定后足肿胀程度,并观察大鼠后肢放射学和踝关节组织病理学变化.结果:与模型组比较,英卡膦酸盐剂量依赖性地降低关节炎分数和后足肿胀程度;大鼠后肢放射学和踝关节组织病理学变化显示,英卡膦酸盐减轻踝与足部骨、关节的变形破坏,X线分数和TRAP阳性细胞计数剂量依赖性的降低.结论:英卡膦酸盐对大鼠佐剂关节炎的关节炎症、肿胀以及结构破坏具有抑制作用,提示英卡膦酸盐可作为类风湿性关节炎的辅助预防治疗药物.     

Exposure of brown Norway rats to diesel exhaust particles prior to ovalbumin (OVA) sensitization elicits IgE adjuvant activity but attenuates OVA-induced airway inflammation.

Exposure to diesel exhaust particles (DEP) during the sensitization process has been shown to increase antigen-specific IgE production and aggravate allergic airway inflammation in human and animal models. In this study, we evaluated the effect of short-term DEP exposure on ovalbumin (OVA)-mediated responses using a post-sensitization model. Brown Norway rats were first exposed to filtered air or DEP (20.6 +/- 2.7 mg/m3) for 4 h/day for five consecutive days. One day after the final air or DEP exposure (day 1), rats were sensitized with aerosolized OVA (40.5 +/- 6.3 mg/m3), and then again on days 8 and 15, challenged with OVA on day 29, and sacrificed on days 9 or 30, 24 h after the second OVA exposure or the final OVA challenge, respectively. Control animals received aerosolized saline instead of OVA. DEP were shown to elicit an adjuvant effect on the production of antigen-specific IgE and IgG on day 30. At both time points, no significant airway inflammatory responses and lung injury were found for DEP exposure alone. However, the OVA-induced inflammatory cell infiltration, acellular lactate dehydrogenase activity and albumin content in bronchoalveolar lavage (BAL) fluid, and numbers of T cells and their CD4+ and CD8+ subsets in lung-draining lymph nodes were markedly reduced by DEP on day 30 compared with the air-plus-OVA exposure group. The OVA-induced nitric oxide (NO) in the BAL fluid and production of NO, interleukin (IL)-10, and IL-12 by alveolar macrophages (AM) were also significantly lowered by DEP on day 30 as well as day 9. DEP or OVA alone decreased intracellular glutathione (GSH) in AM and lymphocytes on days 9 and 30. The combined DEP and OVA exposure resulted in further depletion of GSH in both cell types. These results show that short-term DEP exposure prior to sensitization had a delayed effect on enhancement of the sensitization in terms of allergen-specific IgE and IgG production, but caused an attenuation of the allergen-induced airway inflammatory responses.     

Chemotherapy-induced amenorrhea: influence on disease-free survival and overall survival in receptor-positive premenopausal early breast cancer patients.

BACKGROUND: The aim of this study was to evaluate the influence of early chemotherapy-induced amenorrhea (CIA) on disease-free survival and overall survival in premenopausal patients with receptor-positive early breast cancer treated with adjuvant chemotherapy without any hormonotherapy. PATIENTS AND METHODS: Retrospectively, we reviewed data from 130 premenopausal patients with localized hormone-sensitive breast cancer. These patients were treated between 1985 and 1995 at the same institution. They all underwent a loco-regional treatment and adjuvant chemotherapy. Early CIA was defined as an amenorrhea arising during the first year following the beginning of chemotherapy. Predictors of early CIA were examined. The survival analyses were done using the Kaplan-Meier method and Cox analysis. RESULTS: Median follow-up was 9 years. Mean age was 42.9 +/- 5 years. Ninety-two per cent of patients had histologically-proven positive axillary nodes. Adjuvant chemotherapy contained no anthracycline in 63%. Early CIA occurred during or after adjuvant chemotherapy in 57% of the patients. It was definitive in 91%. In our study, age was the only CIA predictor in univariate analysis. Women who experienced early CIA tend to have a longer disease-free survival, but the difference was not significant. This trend was lost in multivariate analysis, most probably due to the small sample size. The overall survival was not different. CONCLUSION: Although not statistically significant, our results on a very selected population of patients suggest that a chemotherapy-induced amenorrhea might have its own therapeutic effect besides the cytotoxic action of chemotherapy.