VEGF在恶性淋巴瘤患者血清与骨髓中的表达及其临床意义的研究

目的：探讨VEGF在恶性淋巴瘤的微转移检测及治疗等方面的作用。方法：ELISA法检测50例恶性淋巴瘤患者血清VEGF（S-VEGF）和骨髓VEGF（B-VEGF）的表达水平,用8例健康人血清和4例健康人骨髓作对照。结果：恶性淋巴瘤患者S-VEGF浓度的中位数较健康对照者的明显增高;合并白血病或骨髓侵犯的淋巴瘤患者的B-VEGF水平比正常对照组高;临床治疗有效的患者,治疗后S-VEGF和B-VEGF浓度的中位数较治疗前均有明显下降;S-VEGF表达水平与患者年龄和性别均无相关性;而惰性淋巴瘤的S-VEGF水平比侵袭性和高侵袭性的淋巴瘤S-VEGF水平低;Ⅰ、Ⅱ期和Ⅲ、Ⅳ期患者S-VEGF表达水平差异有统计学意义。S-LDH浓度与S-VEGF浓度呈正相关。结论：VEGF在恶性淋巴瘤患者血清和骨髓中的表达,对临床分期、病理恶性程度、肿瘤侵犯程度有一定指导意义;VEGF的检测对恶性淋巴瘤治疗反应的判断有一定价值;VEGF与LDH相似,有望成为判断恶性淋巴瘤预后的新指标。     

Elevation of serum lactic dehydrogenase levels as an early marker of occult malignant lymphoma

Elevated serum lactic dehydrogenase (LDH) levels, 595 to 615 microns/ml (normal less than 225 microns/ml) with predominance of LDH isoenzymes 2 and 3 was the early and only sign of occult malignant lymphoma in three patients. In the first patient, overt lymphoma appeared clinically only 2 months after the finding of elevated serum LDH levels, whereas in the other two asymptomatic patients, pathologic LDH levels were the only clues to the need for further diagnostic investigation. It is concluded that LDH may have a diagnostic value in the preclinical stage of malignant lymphoma. Thus, a patient with no apparent cause for elevated serum LDH levels warrants a thorough work-up including abdominal CT scan and even explorative laparotomy.     

淋巴瘤患者血清淀粉样蛋白A水平的变化及其临床意义

目的:探讨淋巴瘤患者血清淀粉样蛋白A(SAA)水平的变化及其临床意义。方法:回顾279名淋巴瘤患者临床参数,其中非霍奇金淋巴瘤(NHL)191人,霍奇金淋巴瘤(HL)88人。同期90例健康成人作为对照。比较不同人群间SAA差异。分析SAA浓度与淋巴瘤类型、分期、IPI评分和肿瘤负荷是否存在相关性。根据疗效进行分组,对比SAA浓度变化。结果:NHL的SAA浓度为13.2(4.9～60.5)mg/L,HL患者的SAA浓度为71.2(19.6～139.2)mg/L,二者均高于正常对照组6.14(3.9～18.91)mg/L。SAA在淋巴瘤临床特征中有显著差异,且随着疾病的不同阶段而动态变化。在治疗后NHL患者的SAA浓度能更好地反映预后。而HL患者无论是否达到缓解,SAA水平均有下降的趋势。结论:和正常人对比,NHL和HL患者中SAA浓度明显升高,且NHL患者中SAA可辅助反映预后。     

Ovarian involvement as an initial manifestation of malignant lymphoma

An immunohistochemical study of a rare initial manifestation of non-Hodgkin's lymphoma (NHL) in the ovaries is presented. There have been very few reports to date on immunohistochemical studies of lymphoma involving the ovaries. A 53-year-old woman suffering from lower abdominal pain and abnormal genital bleeding was diagnosed as having a tumor in her left ovary by ultrasonic echograms and CT scanning. The patient underwent a simple total hysterectomy and bilateral salpingo-oophorectomies. The tumor, measuring 14 x 10 x 10 cm, was located in the left ovary and extended to the major omentum, mesocolon and left ureter. The histology of the tumor was that of NHL showing diffuse proliferation of small cleaved cells. Immunohistochemical studies of the ovarian tumor showed that the tumor cells were of a B-cell lymphoma nature with LCA+, MB-1+, lambda+, keratin-, IgG-, IgM-, IgA-, kappa-, and MT-1-. Although the main lesion involved the ovary, the case could not be identified definitely as primary lymphoma of the ovary.     

CSF neopterin level as a diagnostic marker in primary central nervous system lymphoma

BackgroundThe diagnosis of primary central nervous system lymphoma (PCNSL) can be challenging. PCNSL lesions are frequently located deep within the brain, and performing a cerebral biopsy is not always feasible. The aim of this study was to investigate the diagnostic value of CSF neopterin, a marker of neuroinflammation, in immunocompetent patients with suspected PCNSL.MethodsWe retrospectively reviewed the characteristics of 124 patients with brain tumor (n = 82) or an inflammatory CNS disorder (n = 42) in whom CSF neopterin levels were assessed. Twenty-eight patients had PCNSL, 54 patients had another type of brain tumor (glioma n = 36, metastasis n = 13, other n = 5), and 13 patients had a pseudotumoral inflammatory brain lesion.ResultsCSF neopterin levels were significantly higher in the patients with PCNSL than in those with other brain tumors (41.8 vs 5.1 nmol/L, P < .001), those with pseudotumoral inflammatory brain lesions (41.8 vs 4.3 nmol/L, P < .001), and those with nontumefactive inflammatory CNS disorders (41.8 vs 3.8 nmol/L, P < .001). In the 95 patients with space-occupying brain lesions, at a cutoff of 10 nmol/L, the sensitivity of this approach was 96% and the specificity was 93% for the diagnosis of PCNSL. The positive and negative predictive values were 84% and 98%, respectively.ConclusionAssessing CSF neopterin levels in patients with a suspected brain tumor might be helpful for the positive and differential diagnosis of PCNSL. A prospective study is warranted to confirm these results.     

VEGF、p53在非霍奇金淋巴瘤患者血清中的表达及其临床意义的研究

目的：探讨VEGF、p53在非霍奇金淋巴瘤（NHL）的微转移检测及治疗等方面的作用。方法：ELISA法检测60例非霍奇金淋巴瘤患者血清VEGF及p53的含量,用50例健康人血清作对照。结果：NHL患者血清VEGF及p53浓度的平均数较健康对照者的明显增高（t=8.23,P〈0.001;t=5.141,P〈0.001）;合并白血病或骨髓浸润的NHL患者的VEGF及p53水平明显高于未有骨髓浸润者;临床治疗有效的患者,治疗后VEGF及p53浓度的平均数较治疗前均有明显下降;VEGF及p53表达水平与患者年龄和性别均无相关性;而惰性淋巴瘤的VEGF、p53水平比侵袭性和高侵袭性的淋巴瘤水平低（P〈0.05）;Ⅰ、Ⅱ期和Ⅲ、Ⅳ期患者VEGF、p53表达水平差异有统计学意义（P〈0.05）。结论：VEGF、p53在NHL患者血清中的表达,对临床分期、病理恶性程度、肿瘤侵犯程度有一定指导意义;VEGF、p53的检测对NHL治疗反应的判断有一定价值,有望成为判断NHL预后的新指标。     

VEGF、p53在非霍奇金淋巴瘤患者血清中的表达及其临床意义的研究

目的:探讨VEGF、p53在非霍奇金淋巴瘤(NHL)的微转移检测及治疗等方面的作用。方法:ELISA法检测60例非霍奇金淋巴瘤患者血清VEGF及p53的含量,用50例健康人血清作对照。结果:NHL患者血清VEGF及p53浓度的平均数较健康对照者的明显增高(t=8.23,P<0.001;t=5.141,P<0.001);合并白血病或骨髓浸润的NHL患者的VEGF及p53水平明显高于未有骨髓浸润者;临床治疗有效的患者,治疗后VEGF及p53浓度的平均数较治疗前均有明显下降;VEGF及p53表达水平与患者年龄和性别均无相关性;而惰性淋巴瘤的VEGF、p53水平比侵袭性和高侵袭性的淋巴瘤水平低(P<0.05);Ⅰ、Ⅱ期和Ⅲ、Ⅳ期患者VEGF、p53表达水平差异有统计学意义(P<0.05)。结论:VEGF、p53在NHL患者血清中的表达,对临床分期、病理恶性程度、肿瘤侵犯程度有一定指导意义;VEGF、p53的检测对NHL治疗反应的判断有一定价值,有望成为判断NHL预后的新指标。     

Residual disease after chemotherapy in aggressive malignant lymphoma

Residual disease in patients with diffuse large B-cell lymphoma after intensive chemotherapy remains a problem. Radiotherapy has been used in some retrospective studies without definitive conclusions. We report the first controlled clinical trial to define the role of radiotherapy in this setting of patients. One hundred and sixty-six patients with diagnosis of diffuse large B-cell lymphoma, high- or high-intermediate clinical risk, with residual disease (defined as tumor mass <5 cm) were randomly assigned to received radiotherapy at the involved field, with 30 Gy delivered in 20 sessions or no radiation (control group). Median follow-up was 135 mo; patients who received radiotherapy have an better outcome. Actuarial curves at 10 yr showed that progressive-free disease was 86% and overall survival was 89%; those were statistical significant when compared to patients who did no received radiotherapy: 32% and 58% respectively, (p<0.001). Toxicity was mild and well tolerated. We concluded that presence of residual mass after chemotherapy in patients with aggressive malignant lymphoma has a worse prognosis, and salvage radiotherapy improves outcome with mild toxicity. We feel that radiotherapy will be considered as necessary treatment in this special group of patients.     

儿童非霍奇金淋巴瘤MDM2和p53蛋白表达的研究

 目的 探讨儿童非霍奇金淋巴瘤（NHL）患者癌基因MDM2和抑癌基因p53的表达与NHL的恶性程度和预后的关系。方法 46例儿童NHL患者作为病例组,12例儿童淋巴结炎患者作为对照组。用免疫组织化学超敏S-P染色法,检测病例组NHL患者、对照组淋巴结炎患者病理组织的MDM2蛋白和p53蛋白的表达情况,阳性细胞为胞核染成黄色~棕黄色,阳性细胞数≥10 %为MDM2免疫组织化学阳性（MDM2蛋白过度表达）;阳性细胞数>5 %为p53免疫组织化学阳性。结果 病例组MDM2蛋白过度表达率为65.2 %,与对照组比较差异有统计学意义（P＜0.01）。p53蛋白阳性率为19.6 %,与对照组比较差异无统计学意义（P＞0.05）。MDM2蛋白过度表达率在病理分类高度恶性、患者血清LDH增高之间差异均有统计学意义（P＜0.05）,与患者的B状态间差异有统计学意义（P＜0.01）。p53蛋白阳性率与病理工作分类、临床分期、B状态、血清LDH之间差异均无统计学意义（P＞0.05）。MDM2蛋白过度表达与p53蛋白阳性之间没有关联性。结论 儿童NHL患者MDM2基因的过度表达率较高;MDM2过度表达与儿童NHL患者的不良状况、不良预后有关;儿童NHL患者p53阳性率较低。     

Low serum pancreatitis-associated protein does not exclude complications in mild acute pancreatitis

Normal serum PAP levels on admission to the hospital in patiens with acute pancreatitis has been proposed to help select the patients who are not going to develop complications. The aims of this study were, first, to assess the specificity of serum pancreatitis - associated protein (PAP) serology test and second, to evalute the usefulness of the test for prediciting complications in acute pancreatitis on admission to the hospital. The sensitivity of the PAP ELISA in patiens with acute pancreatitis on admission to the hospital was 70% and the serum PAP levels significantly higher than in healthy controls (p > 0.0001). However, the serum PAP levels in patients with acute pancreatitis were not significantly different from values in patients with various abdominal diseases (p > 0.58). Serum PAP levels gave good correlation to APACHE II (p = 0.02) and CRP (p = 0.01). Two patients with local complications (necrotizing pancreatitis, pancreatic fluid collection) had elevated serum PAP levels on admission to the hospital (< 100 ng/ml). The diagnostic specififity of PAP ELISA is low. Patients, who develop local complications in acute pancreatitis can not be excluded by normal serum PAP levels on admission to the hospital.     

抗凋亡蛋白Bcl—2在非霍奇金淋巴瘤中的表达,分布及其临床意义

研究抗凋亡蛋白Ｂｃｌ－２在非霍奇金淋巴瘤（ＮＨＬ）中的表达、分布及其临床意义。方法采用４重ＰＡＰ免疫组织化学法,对比分析了１２例反应性淋巴滤泡增生与７１例ＮＨＬ的常规石蜡包埋淋巴结组织中Ｂｃｌ－２蛋白的表达与分布。结果（１）９３．０％Ｔ、Ｂ淋巴细胞性ＮＨＬＢｃｌ－２蛋白阳性。（２）８／９例滤泡中心起源的弥漫型ＮＨＬ中,Ｂｃｌ－２蛋白局限于中心细胞,而中心母细胞多为阴性。（３）５／１０例呈浆细胞样分化趋势的弥漫性大Ｂ细胞ＮＨＬ,Ｂｃｌ－２蛋白表达增强。（４）７例滤泡型ＮＨＬ中,Ｂｃｌ－２蛋白主要定位于瘤性滤泡中央,而其周围则相对稀疏。相反,生理性淋巴滤泡中,Ｂｃｌ－２蛋白则主要分布于套区,生发中心均为阴性。结论Ｔ、Ｂ淋巴细胞ＮＨＬ均能表达Ｂｃｌ－２;Ｂｃｌ－２表达可能与ＮＨＬ分化水平相关;Ｂｃｌ－２蛋白免疫组化染色有助于鉴别反应性淋巴滤泡增生过长与滤泡型淋巴瘤。     

粘连蛋白基因在恶性淋巴瘤中表达的研究

目的　探讨粘连蛋白 (FN)基因在恶性淋巴瘤中的表达及其在肿瘤发生中的作用。方法　运用基因芯片和逆转录聚合酶链反应 (RT -PCR)技术检测 12例胃恶性淋巴瘤细胞中FN基因表达。结果　基因芯片检测显示FN基因在恶性淋巴瘤中表达显著增高 (Cy5 /Cy3>2 .0 ) ,RT -PCR结果与基因芯片相同。结论　基因芯片能够为恶性淋巴瘤的相关基因分析提供特异和可靠的数据。恶性淋巴瘤的发病机理可能与FN基因表达升高有关。     

Minichromosome maintenance protein 6, a proliferation marker superior to Ki-67 and independent predictor of survival in patients with mantle cell lymphoma

Minichromosome maintenance protein 6 (MCM6) is one of six proteins of the MCM family which are involved in the initiation of DNA replication and thus represent a marker of proliferating cells. Since the level of cell proliferation is the most valuable predictor of survival in mantle cell lymphoma (MCL), we investigated lymph node biopsy specimens from 70 patients immunohistochemically with a monoclonal antibody against MCM6. The percentage of MCM6 expressing lymphoma cells ranged from 12.0 to 95.6%, with a mean of 61.0%, and was significantly higher than the percentage of Ki-67-positive cells (P<0.0001). Surprisingly, the ratio of MCM6-positive cells to Ki-67-positive cells was higher than in normal stimulated peripheral blood mononuclear cells, indicating a cell early G1-phase arrest in MCL. A high MCM6 expression level of more than 75% positive cells was associated with a significantly shorter overall survival time (16 months) compared to MCL with a low MCM6 expression level of less than 25% (no median reached, P<0.0001). Multivariate analysis revealed MCM6 to be an independent predictor of survival that is superior to the international prognostic factor and the Ki-67 index. Therefore, aside from gene expression profiling, immunohistochemical detection of MCM6 seems to be the most promising marker for predicting the outcome in MCL.     

恶性淋巴瘤的生物治疗进展

 近几十年来,恶性淋巴瘤的发病率逐年上升,尽管它对化疗非常敏感,新的化疗药物及化疗方案也不断涌现,但其远期生存率仍徘徊在40 % ~ 50 %之间。近20年来,随着免疫学的发展,生物治疗在淋巴瘤治疗中的地位正日益引起关注,并成为其综合治疗的重要组成部分。目前常用于淋巴瘤治疗的生物治疗手段包括：单克隆抗体的治疗、放射免疫治疗、主动免疫治疗、过继免疫治疗、靶向bcl-2的基因治疗、特异性小分子靶向药物治疗等。合理使用这些方法并与其他治疗手段有机地结合将有助于提高淋巴瘤的近期疗效和远期生存率。     

Bilateral primary malignant lymphoma of the ureter

We report the case of a 68-year-old Japanese man who presented with postrenal azotemia due to bilateral upper ureteral stenosis. The patient's right kidney was nonfunctional; therefore, right nephroureterectomy was performed for the purpose of pathologic diagnosis. Histopathologic examination revealed follicular lymphoma with diffuse change in the ureter. With chemotherapy for malignant lymphoma, the stenosis of the left ureter was alleviated, and left renal function was preserved. Primary malignant lymphoma of the ureter is extremely rare. In cases of ureteral stenosis with ureteral wall thickening for which the cause is uncertain, the possibility of malignant lymphoma of the ureter should be considered.     

Bilateral ovarian involvement as the only manifestation of malignant lymphoma

A 16-year-old girl presented with a large pelvic mass. At laparotomy, bilateral ovarian tumors were disclosed and bilateral salpingo-oophorectomy was performed. No evidence of extra-ovarian disease was found. Histopathological examination and histochemical immunoperoxidase studies demonstrated the tumors to be malignant lymphoma of the lymphoblastic type. The patient had radiotherapy and systemic chemotherapy and more than 10 years later she is alive with no evidence of recurrent disease. The rarity of ovarian involvement as the initial manifestation of malignant lymphoma is discussed. The question of whether this patient represents a case of a primary ovarian malignant lymphoma or merely represents a case of ovarian initial manifestation of an occult generalized disease cannot be answered.     

Carmustine, etoposide, cytarabine and melphalan as a preparative regimen for allogeneic transplantation for high-risk malignant lymphoma

Background: The combination of carmustine, etoposide, cytarabine and melphalan (BEAM) is an effective autologous transplantation preparative regimen for lymphoma and has little toxicity, but the feasibility and tolerance of BEAM as a preparative regimen for allogeneic transplantation has not been established.Patients and methods: Thirty adults with primary refractory or recurrent intermediate- or low-grade lymphoma were treated on a prospective phase II study with carmustine 300 mg/m2 i.v. day –6, etoposide 200 mg/m2 i.v. followed by cytarabine 200 mg/m2 i.v. twice daily days –5 to –2, melphalan 140 mg/m2 i.v. day –1, and marrow or blood stem cells from an HLA-identical donor on day 0. Tacrolimus and methotrexate were used to prevent graft-vs.-host disease (GVHD).Results: Median time from transplantation was 20 mos (range 6–32 months). Median maximal regimen-related toxicity grade was 2, and four patients (13%) had a grade 3–4 regimen-related toxicity. Two patients had idiopathic interstitial pneumonitis. One patient had primary graft failure, and a second had autologous reconstitution documented at three months posttransplant. Grades 2–4 acute GVHD occurred in 31%, grades 3–4 in 16%, and chronic GVHD in 54%. Day-100 survival was 70%. Twenty-three patients achieved a complete response. The two-year relapse rate was 23%, survival was 48%, and disease-free survival (DFS) was 42%.Conclusions: BEAM supports engraftment of allogeneic transplants and is a tolerable preparative regimen for allogeneic transplantation for lymphoma.