WT1基因与急性髓系白血病的预后及主动特异性免疫治疗的研究进展

WT1基因位于人类染色体11p13，在80%的急性髓系白血病（acute myeloid leukemia，AML）患者中高表达，是AML预后不良的分子标志，可作为AML预后评估和微小残留病变（minimal residual disease，MRD）监测的有效指标。由于WT1在AML中均有异常高表达，故认为是一种AML抗原，可作为特异性免疫治疗的新靶点。一些小规模的临床试验证实以WT1为靶点的免疫治疗是有效的、安全的，这些免疫治疗可作为那些有高危复发风险及初始标准化疗失败的AML患者的辅助治疗。本文就近几年WT1与AML的预后及有关以WT1为靶点的主动特异性免疫治疗的研究进展予以综述。     

Dermatofibrosarcoma protuberans: a population-based cancer registry descriptive study of 66 consecutive cases diagnosed between 1982 and 2002

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a rare malignant tumour of the skin, with an estimated incidence of 0.8 to five cases per 1 million people per year. OBJECTIVE: To study epidemiological, immunohistochemical and clinical features, delay in diagnosis, type of treatment and outcome of DFSP from 1982 to 2002. METHODS: Using data from the population-based cancer registry, 66 patients with pathologically proved DFSP were included (fibrosarcomatous DFSP were excluded). Each patient lived in one of the four departments of Franche-Comté (overall population of 1 million people) at the time of diagnosis. The main data sources came from public and private pathology laboratories and medical records. The rules of the International Agency for Research on Cancer were applied. RESULTS: The estimated incidence of DFSP in Franche-Comté was about three new cases per 1 million people per year. Male patients were affected 1.2 times as often as female patients were. The trunk (45%) followed by the proximal extremities (38%) were the most frequent locations. DFSP occurred mainly in young adults between 20 and 39 years of age. Mean age at diagnosis was 43 years, and the mean delay in diagnosis was 10.08 years. Our 66 patients initially underwent a radical local excision. Among them, 27% experienced one or more local recurrences during 9.6 years of follow-up. There was one regional lymph node recurrence without visceral metastases. These recurrences were significantly related to the initial peripheral resection margins. We observed a local recurrence rate of 47% for margins less than 3 cm, vs. only 7% for margins ranging from 3 to 5 cm [P=0.004; OR=0.229 (95%, CI=0.103-0.510)]. The mean time to a first local recurrence was 2.65 years. Nevertheless, there was no death due to the DFSP course at the end of the follow-up, and the final outcome was favourable. CONCLUSION: Our study emphasizes the importance of wide local excision with margins of at least 3 cm in order to prevent local recurrence. However, the recent development of inhibitors of signal transduction by the PDGFB pathway should soon modify the surgical strategy, which is often too mutilating.     

Clinical and histopathologic factors related to prognosis in primary squamous cell carcinoma of the vagina

The goal of this retrospective study concerning primary carcinoma of the vagina (PCV) was to analyze clinical and histopathologic prognostic factors in one of the largest known material, which comprised 314 patients. PCV is a rare disease, and the majority of published studies are based on small materials; therefore, the established knowledge concerning prognostic factors is insufficient. Routine treatment is based on irradiation with risk for undertreatment or overtreatment, which leads to unnecessary complications in the absence of prognostic factors. The overall 5-year disease-specific survival rate in this study was 45% and in stage I 75%. In the univariate statistical analysis, several factors correlated significantly with disease-specific survival. However, in the multivariate analysis, there were only three factors that independently could predict poor survival-high age at diagnosis, large tumors (> or =4 cm), and advanced stage. Common background factors with no prognostic significance were prior hysterectomy, other gynecological malignancies, and pelvic irradiation. In conclusion, this study has elucidated three strong prognostic factors that might be considered in the choice of therapy and also for modification of the FIGO guidelines. Increased knowledge concerning complementary biologic markers to discriminate between low- and high malignant tumors is however of great importance.     

Focal peritubular capillary C4d deposition in acute rejection.

BACKGROUND: Diffuse peritubular capillary (PTC) C4d deposition has been shown to be associated with relatively poor graft outcome. The significance of focal PTC C4d staining in the early post-transplant period is uncertain. METHODS: Sixty-five biopsies from 53 patients with acute rejection were graded (Banff '97 criteria), stained for C4d, monocytes and T cells, and divided into three groups according to PTC C4d: (i) focal C4d (F) (14 biopsies, 14 patients), (ii) diffuse C4d (D) (23 biopsies, 15 patients) and (iii) no C4d (N) (28 biopsies, 24 patients). The three groups were compared with respect to a variety of biopsy and clinical parameters including outcome. RESULTS: The incidence of transplant glomerulitis and glomerular monocyte infiltration were significantly greater in F (64% and 2.0+/-2.0) and D (57% and 3.4+/-2.0) than in N (11% and 0.2+/-0.2). A significantly higher proportion of F (93%) demonstrated acute cellular rejection (Banff '97 grade > or = 1A) than did D (35%). The F and D groups included significantly more females (50 and 67%, respectively) than did N (21%). The percentage of patients with a second or third transplant was higher in F (29%) and D (40%) than in N (8%) (P = 0.0589). The proportion of patients with glomerular filtration rate < 30 ml/min at 12, 24 and 48 months was higher in the D and F groups than in the N, and there was a statistically significant increasing trend in odds of this outcome occurring at 48 months across the three groups (D > F > N group) (P = 0.0416). CONCLUSION: The results suggest that the biopsy findings and clinical course in patients with focal PTC C4d staining are similar to those associated with diffuse C4d.     

31例卵巢恶性畸胎瘤临床分析

本文报道了我院收治的卵巢恶性畸胎瘤３１例，随访中２例失访，随访率为９３．５３％。并讨论了卵巢恶性畸瘤的治疗方式为手术加联合化疗，对年轻的Ｉ期患者可行患侧单侧附件切除术，术后化疗极为重要。化疗方法采用ＶＡＣ或ＰＶＢ方案联合化疗，本文还 影响预后的重要因素为临床分期期和病理学特点．     

Health-related quality of life assessed before and during chemotherapy predicts for survival in multiple myeloma

Measurement of health-related quality of life was integrated into a randomized trial (NMSG 4/90) comparing melphalan/prednisone to melphalan/prednisone + interferon α-2b in newly diagnosed multiple myeloma. One of the aims of the study was to assess the prognostic significance of quality-of-life scores, using the EORTC QLQ-C30 questionnaire. Univariate analysis showed a highly significant association with survival from the start of therapy for physical functioning as well as role and cognitive functioning, global quality of life, fatigue and pain. In multivariate analysis, physical functioning and W.H.O. performance status were independent prognostic factors ( P values=0.001 for both) when analysed in a Cox regression model with the somatic variables β-2 microglobulin, skeletal disease and age. The best prediction for survival from the start of therapy was obtained by combining the β-2 microglobulin and physical functioning scores in a variable consisting of three risk factor levels with an estimated median survival of 17, 29 and 49 months, respectively. At a 12 months landmark analysis, the relative risk for patients with physical functioning score 0–20 v 80–100 was 5.63 (99% CI 2.76–11.49), whereas the relative risk for patients without an objective response to chemotherapy compared to those with at least a minor response was 2.32 (99% CI 1.44–3.74). Quality-of-life assessment may be an independent and valuable addition to the known prognostic factors in multiple myeloma.     

Multimodality evoked potentials and early prognosis in comatose patients

In 112 comatose patients somatosensory, visual and auditory evoked potentials were registered within 36 hours after the onset of coma or admission. Main causes of coma were head injury, and intracerebral and subarachnoid haemorrhage. The initial bilateral loss of any evoked potential was associated with a mortality of 98%. Normal somatosensory evoked potentials were associated with a survival rate of 74%, while normal visual and normal auditory evoked potentials had a survival rate of 60% and 66%, respectively. It is concluded that SEPs can be valuable for the prognosis of coma after primary brain lesions.     

高热惊厥214例临床分析

本文分析了214例高热惊厥,结果为:检出率4.35％;男女之比为1.61:1;好发年龄为6个月～6岁(93.5％);首发年龄为6个月～4岁(89.9％);惊厥发作时体温多在39℃以上(74.6％);惊厥发作多在发热后12h内(72.4％);每次热病中惊厥发作1～3次(99.5％);惊厥持续时间多在15min内(91.0％);致惊厥发作的热性疾病以上呼吸道感染为最多;214例中63例复发,其中2例转癫痫,61例尚未发现智力低下或其他异常。从2例转癫痫的临床及脑电图看,提示惊厥发作愈重,持续时间愈长,转癫痫的可能性愈大。     

脑膜瘤端粒酶的活性在判断复发和恶变中的价值

【目的】探讨端粒酶作为脑膜瘤标志物 ,在肿瘤良恶性鉴别、恶性程度评估以及预后预测等方面的意义。【方法】利用TRAP ELISA方法定量检测 6 1例 (份 )肿瘤标本端粒酶的活性 (以ΔA =A4 50 -A690 表示 ) ,结合肿瘤的分类和患者的临床资料 ,分析端粒酶活性作为肿瘤良恶性及判断预后的标记物的可行性。另取正常脑组织标本 2 0例作为对照。【结果】 30例脑膜瘤中 ,2 9例脑膜瘤均未测到端粒酶活性 ;1例端粒酶阳性 (阳性率 3 3%) ,ΔA =0 2 37;全组ΔA平均值 =0 0 49。 15例恶性脑膜瘤中 14例呈端粒酶阳性 (93%) ,ΔA =1 2 37～ 2 5 16 ;1例端粒酶阴性 ,ΔA =0 0 76 ,全组ΔA平均值 =1 6 30。 16例复发性脑膜瘤端粒酶均阳性 (10 0 %) ,ΔA =1 0 34～ 1 4 78,平均 1 2 5 5。脑膜瘤和复发性脑膜瘤、脑膜瘤和恶性脑膜瘤的端粒酶的阳性率和酶活性表达强度方面差异明显 (P分别为 <0 0 0 1、<0 0 1和 <0 0 0 0 5、<0 0 1)。 2 0例正常脑组织中未检测到端粒酶活性。【结论】端粒酶活性的激活在恶性脑膜瘤和复发性脑膜瘤中是较常见的现象。端粒酶作为肿瘤标志物 ,在脑膜瘤的良恶性鉴别、恶性程度评估、预后预测等方面具有重要的意义。     

儿童髓母细胞瘤中VEGFR-2的表达

目的：探讨血管内皮生长因子受体VEGFR－2在儿童髓母细胞瘤中的表达及临床意义。方法：采用免疫组化LSAB法检测84例获随访的儿童髓母细胞瘤中的VEGFR－2表达，按术后生存期3，5，10年分为A，B，C三组，使用Cox回归统计分析。结果：84例儿童髓母细胞瘤中，VEGFR－2阳性表达74例（88．09％），A，B，C三组间VEGFR－2阳性表达分别为100％，88．89％，55．33％（P＜0．01），Cox回归分析显示VEGFR－2是影响生存时间的一个独立的预后因子，它与预后存在负相关关系。结论：VEGFR－2表达水平可作为儿童髓母细胞瘤的预后指标之一。