Ag—NOR对膀胱癌化疗疗效判断的价值

应用Ａｇ－ＮＯＲ染色技术，对１４例处于不同阶段化疗的膀胱移行细胞癌核内ＮＯＲ颗粒进行观察分析，结果表明化疗前，后Ａｇ－ＮＯＲ／核均数有非常显著性差异（Ｐ〈０．０１）而且Ａｇ－ＮＯＲ／核均数下降的幅度与癌组织变程度有关，提示Ａｇ－ＮＯＲ技术可作为判断膀胱癌化疗效果的一种新方法。     

Ag—NOR对原发性骨肿瘤良恶性鉴别及预后估计的意义

应用银染法测定６３例原发性骨肿瘤（恶性２８例，良性２０例，ＧＣＴ１５例）Ａｇ－ＮＯＲ，结果显示：恶性骨肿瘤Ａｇ－ＮＯＲ计数（８．６１±２．３３／核）明显高于良性骨肿瘤（１．２５±０．２０／核），两有高度显性差异（Ｐ值〈０．０１）；两组不同预后的恶性骨肿瘤Ａｇ－ＮＯＲ亦有显性差异（Ｐ值〈０．０１）；ＧＣＴ与恶性骨肿瘤，及不同Ｊａｆｆｅ分级的两组ＧＣＴ之Ａｇ－ＮＯＲ均无显性差异（Ｐ值〉０．０５     

Ag－NOR对原发性骨肿瘤良恶性鉴别及预后估计的意义

应用银染法测定６３例原发性骨肿瘤（恶性２８例，良性２０例，ＧＣＴ１５例）Ａｇ－ＮＯＲ，结果显示：恶性骨肿瘤Ａｇ－ＮＯＲ计数（８．６１±２．３３／核）明显高于良性骨肿瘤（１．２５±０．２０／核），两者有高度显著性差异（Ｐ值＜０．０１）；两组不同预后的恶性骨肿瘤Ａｇ－ＮＯＲ亦有显著性差异（Ｐ值＜０．０１）；ＧＣＴ与恶性骨肿瘤，及不同Ｊａｆｆｅ分级的两组ＧＣＴ之Ａｇ－ＮＯＲ均无显著性差异（Ｐ值＞０．０５），但ＧＣＴ与良性骨肿瘤之Ａｇ－ＮＯＲ有显著性差异（Ｐ值＜０．０１）．本研究提示：（１）Ａｇ－ＮＯＲ是原发性骨肿瘤良恶性鉴别的一项可靠指标；（２）Ａｇ－ＮＯＲ检测有助于对恶性骨肿瘤的预后估计；（３）对所有ＧＣＴ均应考虑恶性的可能，Ｊａｆｆｅ分级不宜作为反映ＧＣＴ生物学行为的标准．     

骨肉瘤Ag—NOR的表达及临床意义

在一组５４例骨肉瘤，研究了肿瘤细胞核仁组成区嗜银蛋白（Ａｇ－ＮＯＲ）的表达，探讨了其与骨肉瘤临床特点和患者预后的关系。结果表明：骨肉瘤肿瘤细胞的Ａｇ－ＮＯＲ表现为核内的黑色或棕黑色大圆形颗粒。骨肉瘤Ａｇ－ＮＯＲ数自２．７～７．０不等。骨肉瘤Ａｇ－ＮＯＲ数与患者年龄、性别、肿瘤部位、症状持续时间、Ｘ线分级、Ｘ线分型和组织学分型无明确相关；与肿瘤最大径和肿瘤外科分期有一定的关系；与核ＤＮＡ含量流式细胞分析提供的Ｓ期细胞百分比、增殖细胞指数和ＤＮＡ倍体水平有明确的相关性；Ａｇ－ＮＯＲ数＜３．５和Ａｇ－ＮＯＲ数＞３．５的患者分组比较，３年生存率有显著差异。     

核仁组成区相关蛋白对乳腺癌诊断和预后的意义

应用光镜和显微图像分析软件，对１７例乳腺良性病变及４６例乳腺癌针吸细胞学标本核仁组成区相关蛋白（Ａｇ－ＮＯＲｓ）进行了检测。结果表明，与乳腺良性病变比较，乳腺癌细胞核内Ａｇ＋ＮＯＲｓ数目显著增多，每个Ａｇ＋ＮＯＲｓ占有平均面积百分比显著减少。乳腺癌转移组与无转移组癌细胞核内ＡｇＮＯＲｓ数目虽无显著差异，但每个Ａｇ－ＮＯＲｓ占有平均面积的百分比差异显著，提示Ａｇ－ＮＯＲｓ检测有助于乳腺良恶性肿瘤的鉴别，且对乳腺癌预后的评估有一定参考意义。     

骨巨细胞瘤Ag—NORs及PCNA的研究

作者采用改良的Ａｇ－ＮＯＲｓ染色技术和ＰＣＮＡ抗体标记对按Ｊａｆｆｅ分级的４８例骨巨细胞瘤细胞核进行研究，以探求Ｊａｆｅ分级方法是否反映骨巨细胞瘤的增生活性。结果显示随病理分级增高，基质细胞内的Ａｇ－ＮＯＲｓ颗料数均值增加，病理分级之间，基质细胞内Ａｇ－ＮＯＲｓ颗粒均值除Ⅱ、Ⅲ级之间判别无显著性（Ｐ值〉０．０５）外，其余各级之间差别均有高度显著性（Ｐ值〈０．０１）。基质细胞内Ａｇ－ＮＯＲｓ计数与Ｐ     

Ag－NOR和电镜观察在骨巨细胞瘤的诊断及预后的意义

应用核仁组成区嗜银蛋白（Ａｇ－ＮＯＲ）染色技术及电镜观察，对４８例骨巨细胞瘤的基质细胞，多核巨细胞进行了分析，并全部进行了随访，有８例多次复发。结果显示，基质细胞Ａｇ－ＮＯＲ计数随病理级别的增高而增高，除Ⅱ～Ⅲ级无显著性差异外，其他各级之间均有显著性。多核巨细胞Ａｇ－ＮＯＲ计数随病理分级的增高而减少，除Ⅰ～Ⅱ级无显著性差异其余各级都有显著性。电镜观察显示骨巨细胞瘤的良恶性特征，复发病例Ａｇ－ＮＯＲ计数有增高趋势。通过本文研究认为Ｊａｆｅ组织学分级如结合Ａｇ—ＮＯＲ技术和电镜观察可以作为指导临床治疗和估价预后的重要指标     

骨巨细胞瘤Ag－NORs及PCNA的研究

作者采用改良的Ａｇ－ＮＯＲｓ染色技术和ＰＣＮＡ抗体标记对按Ｊａｆｆｅ分级的４８例骨巨细胞瘤细胞核进行研究，以探求Ｊａｆｅ分级方法是否反映骨巨细胞瘤的增生活性。结果显示随病理分级增高，基质细胞内的Ａｇ－ＮＯＲｓ颗粒数均值增加，病理分级之间，基质细胞内Ａｇ－ＮＯＲｓ颗粒均值除Ⅱ、Ⅲ级之间差别无显著性（Ｐ值＞０．０５）外，其余各级之间差别均有高度显著性（Ｐ值＜０．０１）。随着病理分级的增高，ＰＣＮＡ阳性表达率有增高的趋势，经卡方检验差别有高度显著性（Ｐ值＜０．０１）。基质细胞内Ａｇ－ＮＯＲｓ计数与ＰＣＮＡ阳性表达率之间存在正相关关系。通过此研究说明Ｊａｆｅ三级病理分级方法尽管在临床上有时与骨巨细胞瘤的侵袭性不相一致，但在病理上仍反映了它的细胞增生活性，尤其Ⅱ、Ⅲ级应同样对待。如果结合临床及Ｘ线表现，此分级方法仍不失为一种指导临床治疗和预测预后的有用指标。     

膀胱癌c—erbB—2癌基因蛋白表达与Ag—NORs定量计数的关系

采用免疫组化方法和胶质银染色技术对５６例膀胱移行上皮癌组织的ｃ－ｅｒｂＢ－２癌基因蛋白表达产物进行检测和对嗜银蛋白核仁组成区（Ａｇ－ＮＯＲｓ）进行定量计数，结果显示：ｃ－ｅｒｂＢ－２蛋白产物表达与膀胱癌的分化程度有关，高分级肿瘤的表达水平高于低分级肿瘤。在ｃ－ｅｒｂＢ－２表达阳性的肿瘤标本中的Ａｇ－ＮＯＲｓ计数（５．２３±０．６５）明显高于ｃ－ｅｒｂＢ－２表达阴性的标本（３．３４±０．４２）（Ｐ〈     

血液透析对多形核白细胞糖皮质激素受体及趋化移动的影响

血液透析对多形核白细胞糖皮质激素受体及趋化移动的影响林萍，刘志民ＡＡＴＵＤＹＯＮＴＨＥＣＨＡＮＧＥＯＦＧＬＵＣＯＣＯＲＴＩＣＯＩＤＲＥＣＥＰＴＯＲＡＮＤＣＨＥＭ－ＯＴＡＣＴＩＣＭＩＧＲＡＴＩＯＮＩＮＴＨＥＰＯＬＹＭＯＲＰ－ＨＯＮＵＣＬＥＡＲＬＥＵＫＯ...     

Validation of silver-stained nucleolar organizer regions for evaluation of invasive character of urinary bladder carcinoma in rats and mice

A series of 8 rat and 16 mouse invasive bladder carcinomas were investigated for the presence of silverstained nucleolar organizer regions (AgNORs) to clarify whether this parameter is applicable to the estimation of their invasive character. With regard to number of AgNORs per cell, neither rat nor mouse carcinomas showed any difference between invasive and noninvasive sites within the same tumor. However, the frequency of cancer cells bearing bizarre dots, irregular in size and shape, was significantly higher at sites of actual invasion. Quantitative data generated using an image analyzer revealed significantly lower values for NOR roundness and significantly larger NOR size in invasive sites than in noninvasive sites in all groups. Double staining for the proliferation marker proliferating cell nuclear antigen (PCNA) and AgNORs was performed on eight rat carcinomas and a close correlation between the two was confirmed. Thus the number of AgNORs in PCNA-positive cells was significantly greater than in PCNA-negative cells. Furthermore, a particularly strong correlation was observed for incidences of PCNA-positive cells and bizarre dots (P<0.01). The quantitative data also demonstrated significant differences in size and shape of dots. It is concluded that AgNORs have diagnostic value for the invasive character of bladder carcinomas.     

Lectin cytochemistry combined with silver colloid staining of argyrophilic nucleolar organizer regions in human gliomas.

Investigation of lectin cytochemical staining of inflammatory cells in human gliomas showed that Allomyrina dichotoma (Allo-A) cytochemistry can reliably distinguish inflammatory from neoplastic cells. Allo-A cytochemistry combined with silver colloid staining of argyrophilic nucleolar organizer regions (Ag-NORs) was performed in human gliomas. Inflammatory cells possessed usually one but sometimes two Ag-NORs and macrophages often possessed several Ag-NORs. The mean Ag-NOR number per nucleus of inflammatory cells ranged from 1.81 to 2.34, and that of neoplastic cells ranged from 2.57 to 3.53 and from 2.84 to 4.46 in low- and high-grade gliomas, respectively. The mean Ag-NOR number per nucleus of inflammatory cells was significantly smaller than that of neoplastic cells (p less than 0.001). Combined Allo-A cytochemical and silver colloid Ag-NOR staining can provide a reliable Ag-NOR number in human gliomas by distinguishing inflammatory cells.     

Does intravesical chemotherapy prevent invasive bladder cancer?

Intravesical chemotherapy has been shown to prolong the interval free of disease and to reduce the tumor recurrence rates in patients with superficial bladder cancer. These observations led us to consider whether a course of intravesical chemotherapy might provide a long-term decrease in the recurrent tumor rate or reduce the incidence of progression to invasive carcinoma. The records of 123 patients entered into a randomized multicenter protocol between 1975 and 1978 were examined. Patients had received a 1-year course of thiotepa or VM26, or transurethral resection alone. Mean followup was 47 months. Patients receiving thiotepa or VM26 had a lower rate of tumor recurrence, expressed as recurrences per 100 patient-months, than those undergoing transurethral resection only (5.25 versus 5.71 versus 7.98) but this was not statistically significant. However, 28 per cent of the controls required therapy besides transurethral resection to control the bladder cancer and 19 per cent died of advanced bladder cancer during followup. Only 15 per cent of the patients undergoing intravesical chemotherapy required therapy other than transurethral resection and only 3 per cent died of advanced carcinoma of the bladder. This finding suggests that intravesical chemotherapy given for 1 year is associated with a significant decrease in the incidence of tumor progression, and provides the justification to conduct future trials with extended followup.     

Intra-arterial chemotherapy via reservoir system for advanced bladder cancer and prostate cancer

A clinical study was performed on the efficacy of intra-arterial chemotherapy using a reservoir system for advanced urological malignancies. The reservoir system was indwelted in the femoral subcutaneous layer by Seldinger's method. Fifteen cases of inoperable complicated advanced bladder cancer and 10 cases of postoperative local recurrent bladder cancer were administered intra-arterial chemotherapy using a reservoir system. Then, 23 cases of local relapsed prostate cancer and two cases of endpocrine-resistant prostate cancer were administered the chemotherapy. The administered anti-cancerous agents were methotraxate, cis-platinum and adriamycin, then 5-FU or carboplatin was administered as maintenance therapy. The mean number of courses of chemotherapy was six for bladder cancer and four for prostate cancer. During stabilization of the local lesion, no distant deterioration was recognized. The overall clinical efficacy was a positive response (PR) and no change (NC): for 18 and 7 cases of bladder cancer, and 11 and 14 cases of prostate cancer, respectively. The median duration of stabilization was 23 months for bladder cancer and 12 months for prostate cancer. The adverse effects were fever than those with systemic chemotherapy.     

紫杉醇及其联合化疗对表浅性膀胱癌化疗敏感性的实验研究

目的探讨紫杉醇及其联合化疗对表浅性膀胱癌的应用前景。方法自１９９５年７月～１９９７年１０月采用肿瘤细胞原代培养技术和ＭＴＴ比色法测定了３０例不同个体膀胱癌细胞及膀胱癌ＥＪ细胞系的化疗敏感性。结果紫杉醇对不同个体的膀胱癌细胞的总敏感率为１６．７％,阿霉素和丝裂霉素分别为１６．７％和２６．７％,三者间差异无显著性,但优于顺铂和噻口替哌;紫杉醇与顺铂或丝裂霉素联合后的协同性最佳,总敏感率均为８３．３％;膀胱癌细胞系的抑制率与不同个体膀胱癌细胞对相同化疗方案的抑制率差异很大。结论紫杉醇联合顺铂或丝裂霉素是可选择的灌注治疗方案;临床上应针对不同病人选择最敏感化疗方案;膀胱癌细胞系的化疗药物敏感性不能代表不同个体膀胱癌细胞的敏感性。     

Risk of bladder tumours after childhood cancer: The British Childhood Cancer Survivor Study

Study Type – Prognosis (population‐based cohort study)
Level of Evidence 2b

OBJECTIVES

To estimate the risk of a second primary tumour (SPT) of the bladder in a cohort of childhood cancer survivors, investigate factors associated with a bladder SPT developing, and compare the risk observed with that expected from the general population.

PATIENTS AND METHODS

The analysis included 17 981 individuals diagnosed with childhood cancer, between 1940 and 1991 in Britain, and surviving for ≥5 years. Ascertainment of a bladder SPT was primarily through the National Health Service Central Registers (NHSCR).

RESULTS

From the NHSCR, 17 bladder SPTs were ascertained; this corresponded to four times (95% confidence interval 2.5–6.4) the expected number of bladder tumours. Standardized incidence ratios (SIRs) varied significantly (P < 0.05) by first primary tumour (FPT) type, follow‐up period, attained age and chemotherapy. The highest SIRs were in those: with heritable retinoblastoma (31.4); treated with chemotherapy (12.0); 0–9 years of follow‐up (10.8); and aged 0–19 years (9.3). The absolute excess risk (AER) for a bladder SPT was 3.7 cases/100 000 survivors per year. The AER varied significantly by FPT type, follow‐up period, attained age and gender. The highest AERs were in those: diagnosed with heritable retinoblastoma (34.0); 20–29 years of follow‐up (14.2); aged 40–49 years (13.0); and male (5.8). Using multivariable Cox regression, FPT and chemotherapy were significantly associated with the risk of a bladder SPT developing. By the age of 55 years, 0.4% of survivors developed a bladder SPT.

CONCLUSION

Although the absolute risk of a bladder tumour within childhood cancer survivors was low, the risk was four times that expected from the general population. Specific groups, e.g. survivors of heritable retinoblastoma and those treated with chemotherapy, were at the highest risk.     

Further study of fibrinogen degradation products in bladder cancer detection

A new, rapid immunoassay kit for assaying fibrinogen degradation products (FDP) was studied in 56 patients with cancer of the bladder and in 48 control patients. The specificity of the kit was demonstrated with a small number of false positive results. In bladder cancer patients with low-stage, small superficial tumors, FDP was positive in 32.2 per cent. The combination of urinary cytologic examination with FDP increased the accuracy of the positive results to 80 per cent. The rapid FDP test supplements the urinary cytology in the follow-up and detection of early bladder cancer.     

Can efficiency of follow-up for superficial bladder cancer be increased?

This study evaluated the efficiency with which follow-up cystoscopy was employed in a population-based cohort of patients with superficial bladder cancer. Subjects were 240 men, aged under 75 years, with superficial bladder cancer first diagnosed in 1982. The median duration of follow-up was 6.1 years. The median (interquartile range) number of follow-up cystoscopies was 8 (5-12) per patient with a patient-specific annual rate of 1.7 (1.2-2.2) per year. The median number of cystoscopies at which recurrent tumour was detected was 2 (0-5) per patient, patient-specific annual rate 0.4 (0.0-1.3) per year of follow-up. Among patients with a single tumour at diagnosis and a negative first check cystoscopy (MRC group 1), the proportion of positive cystoscopies was 0.1 (0.0-0.4). Comparison of observed intervals between cystoscopies with optimal intervals calculated using an optimisation model showed that patients in MRC group 1 were seen sooner in practice than the model predicted, while in practice other patients were seen later than the model predicted. These data support the suggestion that efficiency of follow-up for patients with superficial bladder cancer could be increased by dividing patients into groups with different risks of recurrence and differing follow-up requirements.     

Neo-adjuvant and adjuvant treatment of locally invasive bladder cancer

Since Sternberg et al. in 1985 first published preliminary results of polychemotherapy in patients with metastatic bladder cancer, it became apparent that transitional carcinoma of the bladder is highly responsive to chemotherapy. Response rates up to 70% with combination therapy regimens like methotrexate, vinblastine, doxorubicin or adriamycin and cisplatin promised that transitional carcinoma might be able to cure even in advanced stages. Chemotherapy has either been applied prior to the local treatment (such as radical cystectomy or radiotherapy) in a neo-adjuvant regimen, or after local therapy in an adjuvant regimen. Although a large number of studies have been published in the past 20 years, the role of the different chemotherapeutic approaches has not been clearly defined. Therefore, neither neo-adjuvant nor adjuvant chemotherapy can be recommended as 'gold standard' treatment for advanced bladder cancer.     

BCG in management of superficial bladder cancer

Superficial bladder cancer and particularly carcinoma in situ has the potential for invasiveness for which the treatment is cystectomy with a resultant disappointing 50 per cent five-year survival and urinary diversion with a certain diminished quality of life. BCG therapy is a new method of treating aggressive superficial bladder cancer with better response rates than conventional chemotherapy. It may be immunologically mediated and, if so, may be the first major success of a therapeutic modality that offers less morbidity than the currently standard options of surgery, radiotherapy, or chemotherapy.