弥散加权成像对鉴别前列腺癌和前列腺增生的意义

目的：探讨前列腺弥散加权成像测得的ADC值结合常规MRI对鉴别前列腺癌和前列腺增生的价值。方法：选择前列腺增生病人15例,前列腺癌病人10例,分析采用b值为1000的ADC图及常规MR图像,结合常规MRI在ADC图上选取感兴趣区测量前列腺癌（PCa）、前列腺增生（BPH）外围带（PZ）和前列腺增生中央带（CG）的ADC值。比较差异性并分析重叠情况。结果：前列腺增生表现为信号不均,增生结节有的为T2WI高信号,有的为T2WI低信号,前列腺癌有时与增生结节难以鉴别。PCa的ADC值（0.67±0.06）×10-3mm2/s,前列腺增生外围带（PZ）的ADC值（1.52±0.18）×10-3mm2/s,前列腺增生中央带（CG）的ADC值（1.05±0.25）×10-3mm2/s,BPH的PZ与PCa及BPH的CG与PCa均有显著差异,BPH的PZ与PCa间无重叠,BPH的CG与PCa间有少量重叠。结论：DWI对鉴别前列腺癌和前列腺增生有意义,但由于分辨力的限制,测量ADC值时要参照常规MRI以使选取的区域更准确。     

双指数DWI对前列腺外周带局限性癌的诊断价值：与单指数DWI对照

背景与目的：随着前列腺特异性抗原(prostate-specific antigen,PSA)筛查的推广,越来越多的前列腺癌初诊时尚处于局限性阶段,但目前常规的单指数弥散加权成像(diffusion-weighted imaging,DWI)对局限性前列腺癌与良性病变的鉴别有一定困难。该研究旨在应用双指数函数模型探究外周带局限性前列腺癌及慢性炎性反应的水弥散特性,比较前列腺癌、前列腺炎和正常组织的双指数参数的差异,评价双指数DWI鉴别局限性前列腺癌与前列腺炎的诊断效能并与单指数DWI相比较。方法：经手术病理证实的前列腺局限性癌16例,穿刺证实的前列腺炎性反应患者14例,行常规DWI(b值为0和1000 s/mm2)和一项10个b值(0~3000 s/mm2) DWI检查。测量前列腺癌、前列腺炎及正常组织的单指数表观弥散系数(apparent diffusion coefficients,ADC)、快弥散系数(fast ADC,ADCf)、快弥散系数比例(f)和慢弥散系数(slow ADC,ADCs)并进行比较。应用受试者工作特征(receiver operating characteristic,ROC)曲线比较各参数鉴别良恶性病变的准确性。结果：共测量和计算18处前列腺癌、18处前列腺炎性反应和37处前列腺外周带组织的单、双指数参数。前列腺癌ADC[(0.83±0.11)×10-3 mm2/s]低于其他组织(P<0.01)。前列腺炎ADC[(1.45±0.19)×10-3 mm2/s]低于正常外周带组织[(1.67±0.31)×10-3 mm2/s,P<0.01]。前列腺癌的ADCf[(1.54±023)×10-3 mm2/s]、f[(45.8±5.4)%]及ADCs[(0.52±0.15)×10-3 mm2/s]明显低于其他组织(P<0.01)。与正常外周带组织的ADCf[(3.90±0.40)×10-3 mm2/s]、f[(67.3±8.2)%]和ADCs[(1.51±0.36)×10-3 mm2/s]相比,前列腺炎的ADCf[(3.06±0.49)×10-3 mm2/s]、f[(47.9±3.9)%]和ADCs[(0.91±0.29)×10-3mm2/s]明显降低(P<0.01)。鉴别前列腺癌与前列腺炎时,ADC和ADCf的曲线下面积(area under the curve,AUC)约为0.96和0.94,差异无统计学意义(P>0.01),f和ADCf的AUC、灵敏度及特异度明显低于ADC(P<0.01)。结论：双指数DWI可为局限性前列腺癌、炎性反应及正常组织提供特征性的参数ADCf、f和ADCs,且ADCf鉴别前列腺癌与良性病变的准确性与ADC相当。因此,双指数DWI对于提高局限性前列腺癌的诊断效果有较大意义。     

磁共振弥散加权成像诊断肝内胆管细胞癌的研究分析北大核心CSCD

背景与目的:肝内胆管细胞癌(intrahepatic cholangiocarcinoma,ICC)较少见,近年来发病率持续上升。本研究旨在探讨磁共振弥散加权成像(diffusion-weighted imaging,DWI)对ICC的诊断价值。方法:18例经手术病理证实ICC作常规磁共振成像及DWI成像(b=0,600 s/mm2),分析ICC常规影像特点,定量分析和比较ICC肿瘤实质区与正常肝组织、ICC中肝脓肿区与肿瘤坏死囊变区DWI信号特点及表观扩散系数差异。结果:18例病变T1WI均呈低信号,T2WI均呈较高信号,增强后早期强化多不明显,延迟期呈环状、向心性充填式强化。DWI图像上18例ICC肿瘤实质区均呈高信号,ADC值为(1.32±0.15)×1010-3mm2/s;正常肝实质区ADC值(1.54±0.15)×10-3mm2/s,3例肝脓肿区ADC值(0.09±0.04)×10-3mm2/s,7例肿瘤坏死囊变区ADC值(1.73±0.17)×10-3mm2/s。ICC肿瘤实质区与正常肝组织间、肝脓肿区与肿瘤坏死囊变区间ADC值差异均具有统计学意义(t=4.62,P<0.001,t=3.73,P<0.05)。结论:DWI可作为常规MRI诊断ICC的重要补充方法,并对ICC合并肝脓肿与肿瘤坏死区有鉴别意义。     

磁共振弥散加权成像评价肝癌冷冻术后近期疗效

目的:探讨采用磁共振弥散加权成像(MRI-DWI)对鉴别肝细胞性肝癌(HCC)冷冻术后肿瘤坏死、残留的应用价值.方法:对接受冷冻治疗的27例肝癌患者共30个病灶行T1 WI、T2WI常规MRI平扫、DWI序列及动态增强扫描.观察肿瘤冷冻前、后MRI信号改变.对HCC一般特征与ADC值的相关性进行分析.比较冷冻前后正常肝脏、肿瘤组织及术后坏死、残留组织的ADC值.结果:冷冻坏死的肝肿瘤组织在T1WI图中呈稍低或稍高信号,T2WI呈低或等信号,DWI呈低信号,动态增强无强化.活性残留肿瘤14个(其中12个肿瘤直径＞5.0 cm),残留率为46.7％.b值=800 s/mm2时,ADC值由低到高依次为:术后残留肿瘤组织(0.98±0.17)×10-3 mm2/s、术前肝肿瘤组织(1.03±0.20)×10-3 mm2/s、正常肝组织(1.14 ±0.07)×10-3mm2/s、术后坏死肿瘤组织(2.07±0.23)×10-3 mm2/s.肝肿瘤组织与对照组正常肝组织ADC值相比,差异有统计学意义(P=0.016).肝肿瘤组织ADC值与肿瘤大小不相关(r=-0.10,P=0.614),与直径范围,肿瘤分期、是否远端转移无关(P＞0.05)、与分化程度有关(P＜0.05).肿瘤坏死区ADC值与术前肿瘤组织相比,差异均有显著统计学意义(P＜0.01).残留组织ADC值与坏死组织及正常肝组织相比,差异均有统计学差异(P＜0.01,P=0.03),与肿瘤组织相比无统计学差异(P=0.192).结论:MRI-DWI能有效鉴别肝癌冷冻术后的病灶坏死及残留,为进一步的临床诊治提供影像学依据.     

MRI影像组学在鉴别前列腺癌与前列腺增生中的临床应用价值

目的:探讨基于T2WI与表观扩散系数(apparent diffusion coefficient,ADC)的影像组学模型对前列腺癌(prostate cancer,PCa)和前列腺增生(benign prostatic hyperplasia,BPH)的鉴别诊断应用价值。方法:回顾性分析经穿刺活检病理证实的72例PCa患者与64例BPH患者的临床资料及原始MRI图像。使用ITK-SNAP软件手动勾画整个肿瘤(不包括囊变、出血、坏死及钙化)生成三维体积(VOI),采用FAE软件分别从T2WI与ADC图像提取高通量影像组学特征,应用Pearson相关性分析及循环特征消除(RFE)方法进行特征选择,使用支持向量机(SVM)作为分类器构建影像组学模型。采用分层随机抽样的方法将所有病例按7∶3分成训练集与验证集,通过绘制受试者工作特征(ROC)曲线及校准曲线分析评估各个影像组学模型的鉴别诊断效能与校准能力,并使用Delong检验评价模型间的差异。结果:经过特征选择,分别使用12、15、11个图像特征构建基于T2WI/ADC/T2WI+ADC的影像组学预测模型。训练集中T2WI/ADC/T2WI+ADC影像组学模型的ROC曲线下面积(AUC)分别为0.88、0.92、0.96,验证集中T2WI/ADC/T2WI+ADC影像组学模型的AUC分别为0.85、0.89、0.91。Delong检验显示T2WI+ADC联合影像组学模型鉴别诊断效能显著高于单个序列模型,校准曲线显示联合影像组学模型具有较好的预测能力。结论:基于T2WI+ADC的联合影像组学模型有助于术前鉴别PCa和BPH。     

良性前列腺增生及前列腺癌的ADC值与PAP、P504S、PSA表达的相关性研究

目的：探讨良性前列腺增生和前列腺癌的ADC值与前列腺相关标志物PAP、P504S、PSA表达的关系。方法收集经病理证实的65例前列腺疾病患者,其中良性前列腺增生30例,前列腺癌35例。病理检查前3个月内均行前列腺MRI、DWI检查,采用单次激发EPI序列,b值为0 s/mm2和800 s/mm2,并采用免疫组化检测组织标本中PAP、P504S、PSA的表达,分析ADC值与PAP、P504S、PSA表达的关系。结果良性前列腺增生和前列腺癌的ADC值分别为（1.73±0.21）×10-3 mm2/s和（1.34±0.15）×10-3 mm2/s,差异具有统计学意义（t=8.545,P=0.000）。PAP和PSA在良性前列腺增生和前列腺癌中均表达,差异无统计学意义（P均＞0.05）,P504S在前列腺癌中的表达显著高于良性增生（Z=-7.055,P=0.000）,双变量相关分析显示ADC值与P504S的表达呈显著负相（Spearman's相关系数r=-0.654,P=0.000）;结论 PAP和PSA不能区别前列腺良恶性病变;P504S可以作为前列腺癌标志物;ADC值可以定量评价良性前列腺增生和前列腺癌,且与P504S存在负相关,可以作为前列腺良恶性病变MRI诊断的参考指标。     

12例肝脏肉芽肿的MRI表现

目的探讨肝脏肉芽肿的MRI表现.提高对本病诊断的准确性.方法对天津医科大学附属肿瘤医院2004年4月～2007年10月经手术病理证实的12例肝脏肉芽肿进行回顾性分析.其中肝脏结核7例,肝脏肺吸虫病2例,特发性肉芽肿3例.全部病例均行上腹MRI检查,序列包括T1WI、TWI、动态增强MRI(DCE-MRI)和弥散加权(DWI).结果12例肝脏肉芽肿共13个病灶,其中4个为肉芽肿中早期病灶,9个为纤维化期病灶.1)肉芽肿中早期病灶T1WI呈低信号,T2WI呈较高信号,边界模糊,DCE-MRI于动脉期呈不均匀环形强化,门静脉期及延迟期强化程度逐渐增加,DWI呈稍高信号,ADC值为(1.347±0.379)×10-3(mm2/s),ADC比率为1.103±0.165.2)纤维化期病灶T1WI呈低信号,T2WI呈等信号.边界清楚,DCE-MRI无明显强化或仅边缘线样强化,DWI呈稍高信号,ADC值为(1.382±0.398)×10-3(mm2/s),ADC比率为0.978±0.116.结论肝脏肉芽肿的MRI信号表现能反映其所处的病理时期.并可以与肝脏其它肿物鉴别,因而MRI在肝脏肉芽肿诊断中具有较高价值.     

磁共振扩散加权成像在前列腺癌诊断中的价值

目的探讨磁共振扩散加权成像对前列腺癌的诊断价值并寻找诊断前列腺癌的适宜阈值。方法 74例前列腺癌疑诊患者行3.0 T MR常规平扫及DWI成像。测量ADC map图中每侧外周带的ADC低值。外周带穿刺发现腺癌为阳性组,无肿瘤证据为阴性组。比较阴性组与阳性组,分化较好腺癌组(Gleason评分2～6分)与分化较差腺癌组(Gleason评分7～10分)的ADC低值差异。以ADC低值预测外周带穿刺阳性率,绘制ROC曲线。结果74例患者中146个前列腺侧叶(阴性组50,阳性组96)获得组织学证实,其中分化较好腺癌(Gleason评分2～6分)17个,分化较差腺癌(Gleason评分7～10分)79个。阳性组与阴性组间ADC低值差异有统计学意义(0.92×10-3±0.22×10-3 mm2/s vs 1.48×10-3±0.28×10-3 mm2/s,t=12.27,P=0.00)。分化较好腺癌组与分化较差腺癌组差异有统计学意义(1.04×10-3±0.20×10-3 mm2/s vs 0.89×10-3±0.21×10-3 mm2/s,t=2.60,P=0.01)。分化较好腺癌组与阴性组ADC低值差异亦有统计学意义(t=5.91,P=0.00)。以ADC低值预测外周带穿刺阳性率,ROC曲线下面积为0.95(P=0.00),最佳临界值为1.15×10-3mm2/s,此时判断穿刺阳性的敏感度为85.4%,特异度为92.0%。结论 MR DWI出现对于前列腺癌的诊断具有较高价值,ADC低值小于1.15×10-3mm2/s可能是较适宜的诊断界值。     

磁共振扩散加权成像在肾细胞癌脑转移诊断中的应用

目的:探讨磁共振扩散加权成像（MRI DWI）在肾细胞癌（RCC）脑转移诊断中的应用价值。方法:采用回顾性研究方法分析2014年2月至2016年5月在我院诊治的140例RCC患者,所有患者都给予常规MRI T1WI与T2WI序列诊断,同时给予DWI序列的ADC值测定与诊断价值判定。结果:所有患者的MRI图像均显示清晰,病理确诊为RCC脑转移40例,RCC 100例。39例RCC脑转移患者的T2WI序列表现为高信号,36例T1WI序列表现为高信号;78例RCC患者的T2WI序列表现为高信号,72例T1WI序列表现为高信号,对比差异都有统计学意义（P＜0.05）。140例患者肾实质ADC值是（2.21±0.32）×10-3 mm2/s,同时,患者肾脏实性肿瘤ADC值是（1.54±0.37）×10-3 mm2/s,对比差异有统计学意义（t=4.298,P＜0.05）;RCC患者的ADC 值为（1.26±0.21）×10-3 mm2/s,RCC脑转移患者的ADC 值为（1.59±0.30）×10-3mm2/s,RCC脑转移的ADC 值明显高于RCC患者（P＜0.05）。将阈值设定为1.355×10-3 mm2/s,通过DWI对RCC患者的脑转移进行诊断,得出其特异性为92.1%,敏感性为85.0%。结论:在诊断RCC患者的脑转移时,ADC值和DWI可以提供重要依据,两者有很好的应用价值。     

3.0T MR小视野扩散加权成像联合68Ga-PSMA-11 PET-CT对前列腺癌的诊断价值

目的 研究3.0T MR小视野扩散加权成像(rFOV DWI即FOCUS)联合⁶⁸Ga-前列腺特异膜抗原(PSMA)-11 PET/CT对前列腺癌的诊断价值。方法 前瞻性研究90例疑似前列腺癌患者,均行3.0T MR FOCUS与⁶⁸Ga-PSMA-11 PET/CT检查,然后行手术或穿刺活检的病理检查。将两种检查方式分别得到的ADC、SUV_max值作为诊断指标,计算SUV_max/ADC比值,采用受试者工作特征(ROC)曲线分析前列腺癌诊断效能。结果 90例患者经病理检查确诊49例前列腺癌,41例前列腺增生。前列腺增生的ADC值、SUV_max、SUV_max/ADC分别为(1.24±0.28)×10^-3mm²/s、5.86±2.71、5.41±3.80,前列腺癌分别为(0.88±0.23)×10^-3mm²/s、16.63±9.67、22.73±18.21,前列腺癌的ADC...     

Toxicology and pharmacokinetics of (1,1-bis(aminomethyl)cyclohexane)oxalatoplatinum(II) (TNO-38)

Preclinical studies on toxicology and pharmacokinetics were performed for (1,1-bis(aminomethyl)cyclohexane)oxalatoplatinum(II) (TNO-38) in rats and a dog after ld₁₀ and ld₅₀ assessment in mice. In drug-treated rats, ura and creatinine concentrations were 1,4-1.9 times those in control rats. Histopathology showed necrosis of tubular epithelium of the kidneys, which was comparable to damage observed after treatment with cisplatin (CDDP), and extensive necrosis of crypt epithelium, especially in the ileum.Similar to CDDP, TNO-38 was emetic in the dog. Non-specific subacute inflammatory changes were observed in the ileum. Renal damage was much less pronounced.Half-lives of distribution and elimination were 6.2 min and 5.2 days, respectively. The cumulative excretion of Pt in urine over 1 and 7 days after drug treatment was 38.3 and 49.3% of the dose, respectively. Twelve weeks after drug administration, Pt concentrations were highest in kidneys and liver.TNO-38 is adequately water soluble. Its reported antitumour activity is consistently lower than that of CDDP. The drug's toxicity was, in general, comparable to that of CDDP. Its pharmacokinetic profile was very similar to that of CDDP. It is concluded that TNO-38 should probably not be further evaluated in clinical studies.     

Clinical trials of Herceptin(R) (trastuzumab)

This report summarises the clinical efficacy and safety findings from clinical trials of the new anti-HER2 monoclonal antibody Herceptin(R) (trastuzumab). Data from pivotal trials indicate that trastuzumab is active when added to chemotherapy in patients with advanced metastatic breast cancer. In particular, the combination significantly prolonged the median time to disease progression, increased the overall response rate, increased the duration of response, and improved median survival time by approximately 25% compared with chemotherapy alone. Furthermore, trastuzumab is active as a single agent in women with HER2-positive metastatic breast cancer, inducing durable objective tumour responses. In total, 15% of patients who had received extensive prior treatment for metastatic disease had an objective response. The median duration of response was 9.1 months following administration of single-agent trastuzumab. Notably, 2% of patients were free of disease progression at 6 months. The safety profile of trastuzumab either given alone or in combination was favourable.     

Antitumor effects of three platinum complexes, (-)-(R)-2-aminomethylpyrrolidine(1,1-cyclobutanedicarboxylato)-platinum (II) monohydrate (DWA2114R), cis-diammine-(1,1-cyclobutanedicarboxylato)platinum(II) (CBDCA) and cis-diamminedichloroplatinum(II) (CDDP), in mice.

(-)-(R)-2-Aminomethylpyrrolidine(1,1-cyclobutanedicarboxylato++ +)platinum(II) monohydrate (DWA2114R), cis-diammine(1,1-cyclobutanedicarboxylato)platinum(II) (CBDCA) and cis-diamminedichloroplatinum(II) (CDDP) were compared for their antitumor effects and nephrotoxicity-inducing activities at the same dosage (1/8, 1/4, 1/3, 1/2, 2/3 or 3/4 of the LD10 or LD10) on the basis of their intravenous lethal doses in mice. DWA2114R was effective against murine tumor lines, Colon 26 and Colon 38 carcinomas, M5076 ovarian sarcoma and P388 L1210 leukemias, implanted subcutaneously (s.c.). Triple injection every other day of DWA2114R was more effective than a single injection at each sublethal dose. The antitumor effects of DWA2114R against these tumors were more effective than or were similar to those of CBDCA and CDDP. The antitumor effect against CDDP-resistant L1210 leukemia implanted s.c. was only observed in the treatment of DWA2114R, but not in CBDCA and CDDP. No excellent antitumor effects of three platinum complexes were observed against Lewis lung carcinoma and B16 melanoma implanted s.c. even at triple injection every other day, and no effect was obtained against Meth-A fibrosarcoma under similar conditions. While the treatment of CDDP showed marked increases in levels of blood urea nitrogen and of urinary protein and sugar at effective doses in the antitumor evaluations, the treatment of DWA2114R as well as CBDCA showed no increase in these parameters. These results indicate that DWA2114R represents a desirable second generation antitumor platinum complex.     

Synergism of cytotoxicity between cis-diaminedichloro-platinum-(ii) and cis-diamine(1,1-cyclobutanedicarboxylate)-platinum-(ii)

In an attempts to increase the antitumor effect and to reduce normal tissue toxicity, the combined cytotoxic effect of cis-Diamminedichloroplatinum (II) (CDDP) and cis-diammine(1,1-cyclobutane dicarboxylate) platinum (II) (CBDCA) was investigated using HeLa and colon 26 cell lines and the combination index (CI). Cytotoxicity of the combination of CDDP and CBDCA on 27 surgically resected specimens of human gastric and colorectal adenocarcinomas was also evaluated using the in vitro succinate dehydrogenase inhibition (SDI) test. The CI values varied with the dose ratio examined (1:1-1:6) of CDDP and CBDCA, with findings that CI<1, synergy, was obtained at fraction affected (Fa)>0.75 for HeLa cells and at Fa<0.9 for colon 26 cells in cases of a dose ratio of 1:1 to 1:2. Of all 27 clinical human adenocarcinomas, the succinate dehydrogenase (SD) activity was significantly lower in cancer cells concomitantly exposed to both CDDP and CBDCA than in those exposed to either drug alone. These positive effects of a combination of two platinum analogues on human malignant tissues have heretofore not been reported, which would warrant the clinical application of this combination for human malignant tumors.     

Non-surgical (medical) treatment of hepatocellular carcinoma (HCC)

Choice of treatment for HCC depends mainly on the size of tumor and patient's liver function because more than 80% of HCC patients are associated with liver cirrhosis. Percutaneous ethanol injection therapy (PEIT), transcatheter arterial embolization (TAE) and intraarterial infusion chemotherapy are, at present, commonly used treatments for HCC in Japan. PEIT is a safe and reliable treatment, in which absolute ethanol is injected to the tumor through a fine needle under US guide. PEIT is indicated for tumors of small size, which can not be removed surgically. The survival rate of PEIT for small liver cancer, less than 2 cm in diameter, is similar with the one of surgically removed cases. TAE is indicated for advanced HCC. Chemoembolization with Lipiodol is commonly used with good result. After TAE has been often performed, the survival rate of HCC patients was dramatically increased. In future, TAE combined with percutaneous transhepatic portal embolization or PEIT would be applied more often to obtain complete destruction of the lesion for advanced HCC. Intraarterial infusion chemotherapy is indicated for advanced HCC, in which TAE can not be performed. MMC, ADM and CDDP are commonly used anti-cancer drugs. Recently frequent infusion of these drugs has become possible by using implantable reservoir with good result. We have performed chemosensitivity test by SRCA for HCC specimens obtained by biopsy using a fine needle.     

In vitro evaluation of dichloro-bis(pyrazole)palladium(II) and dichloro-bis(pyrazole)platinum(II) complexes as anticancer agents

Introduction  Cisplatin (cis-diamminedichloroplatinum) was first identified for its anti-bacterial activity, and was later also shown to be an efficient anticancer agent. However, the therapeutic use of this anticancer drug is somewhat limited by its toxic side effects, which include nephrotoxicity, nausea, and vomiting. Furthermore the development of drug-resistant tumours is commonly observed following therapy with cisplatin. Hence there is a need for improved platinum derived drugs to overcome these limitations. Aims  Apoptosis contributes significantly to the cytotoxic effects of anticancer agents such as cisplatin; therefore in this study the potential anticancer properties of a series of pyrazole palladium(II) and platinum(II) complexes, [(3,5-R₂pz)₂PdCl₂] {R = H (1), R = Me (2)} and [(3,5-R₂pz)₂PtCl₂] {R = H (3), R = Me (4)}, were evaluated by assessment of their pro-apoptotic activity. Methods  The induction of apoptosis was measured in CHO cells by the detection of phosphatidylserine (PS) exposure using the annexin V and APOPercentage™ assays; DNA fragmentation using the Terminal deoxynucleotide transferase dUTP Nick End Labelling (TUNEL) assay; and the detection of activated caspase-3. Results  The platinum complexes were shown to be considerably more active than the palladium complexes, with complex 3 demonstrating the highest level of cytotoxic and pro-apoptotic activity. The LD₅₀ values for complex 3 and cisplatin were 20 and 70 μM, respectively, demonstrating that the cytotoxic activity for complex 3 was three times higher than for cisplatin. Various human cancer cell lines, including CaSki, HeLa, as well as the p53 mutant Jurkat T cell line were also shown to be susceptible to complex 3. Conclusions  Collectively, this in vitro study provides insights into action of palladium and platinum complexes and demonstrates the potential use of these compounds, and in particular complex 3, in the development of new anticancer agents.     

Initial (prefibrotic) stages of idiopathic (primary) myelofibrosis (IMF) - a clinicopathological study.

A clinicopathological follow-up study including sequential bone marrow biopsies was performed on 79 patients with idiopathic (primary) myelofibrosis (IMF) to characterize initial (prefibrotic) stages and to elucidate whether development of fibrosis was accompanied by corresponding clinical findings. For this purpose our cohort of patients was divided into two groups of which the first presented with the generally accepted signs and symptoms of IMF (group I; n = 60). Most patients of the second group (group II; n = 19) showed mild to moderate therapy-refractory anemia, minimal to slight splenomegaly and frequently thrombocytosis, but no bone marrow fibrosis at onset. Hematopoiesis was consistent with a striking hypercellularity in comparison to the age-related involution by adipose tissue, a conspicuous clustering and histotopographic dislocation of megakaryocytes, a neutrophil granulocytic proliferation and a reduction of erythropoietic islets with arrest of maturation. Most remarkable was the dysplastic cytology of megakaryocytes with a definitive deviation of differentiation resulting in bizarre forms. Follow-up examinations revealed that at later stages group II patients were not distinguishable from the first group with more advanced IMF. For this reason, these patients were regarded as presenting initial, prefibrotic IMF characterized by distinctive bone marrow features at the beginning. The prominent abnormalities of megakaryopoiesis together with the granulocytic proliferation were extremely helpful to differentiate prefibrotic IMF with accompanying thrombocythemia from essential thrombocythemia (ET). Dynamics of fiber progression were calculated by regarding increase in density per time. Speed of progression during the first year of observation proved to be significantly higher in group II patients with prefibrotic IMF in comparison to full-blown cases (group I). In conclusion, with respect to prospective clinical trials, diagnostic criteria for IMF should be re-evaluated by also taking initial, prefibrotic stages into account.