血浆游离型甲氧基肾上腺素类物质检测正常的嗜铬细胞瘤和副神经节瘤的临床特点

目的: 分析散发嗜铬细胞瘤和副神经节瘤(pheochromocytoma and paraganglioma,PPGL)患者中血浆游离型甲氧基肾上腺素类物质(metanephrines,MNs)正常者的临床特点,MNs已作为PPGL的首选检测方法在临床中广泛应用,MNs正常的PPGL较少见。方法: 选择2015年3月—2020年1月于北京大学第一医院行泌尿外科手术,病理确诊为PPGL的散发患者共104例,所有患者均有术前血浆游离型MNs检测结果,其中8例(7.69%)MNs正常。回顾MNs正常患者的就诊原因,临床表现,术前检测血浆游离型MNs、3-甲氧基酪胺(3-methoxytyramine, 3-MT)、血儿茶酚胺和嗜铬粒蛋白A(chromograninA, CgA)的结果,影像学表现,术前诊断,术前用药准备,术中血压波动情况及肿瘤组织病理学特点,并与同期MNs升高的PPGL患者相比较。对MNs正常患者进行术后随访。结果: MNs正常的8例PPGL患者中,最常见的临床症状为多汗(3/8)、腰腹痛(3/8)、头痛(2/8)、心悸(2/8)和疲乏(2/8)。对比MNs正常组和升高组患者的其他生化检验结果,血3-MT、儿茶酚胺诊断阳性率组间差异无统计学意义,血浆CgA诊断阳性率在MNs正常组显著下降(2/5 vs.41/43,P=0.005)。两组患者增强CT出现典型表现的比例差异无统计学意义。在8例MNs正常患者中,6例因明确的PPGL既往史,或典型的症状及CT表现,3-MT、CgA升高,PET-CT阳性等原因诊断为PPGL,2例误诊为无功能腺瘤或原发性醛固酮增多症。全部MNs正常患者均应用α受体阻滞剂术前准备,其中1例出现术中平均动脉压<60 mmHg。8例术后随访的中位时间为1.5(0.5~4.5)年,增强CT检查均未见新发肿瘤证据。2例MNs正常患者术后复查3-MT和(或)CgA降至正常。结论: 对于出现PPGL典型症状的肾上腺或腹膜后肿瘤患者及有PPGL既往史患者,MNs检测正常不能作为排除PPGL的充分依据。血3-MT、儿茶酚胺、CgA及影像学检查或对PPGL的诊断有帮助。怀疑MNs正常的PPGL患者推荐应用α受体阻滞剂术前准备,但应避免过量。MNs正常患者的术后随访应重点监测术前阳性的生化指标。     

血浆游离型甲氧基肾上腺素类物质检测正常的嗜铬细胞瘤和副神经节瘤的临床特点

目的: 分析散发嗜铬细胞瘤和副神经节瘤(pheochromocytoma and paraganglioma,PPGL)患者中血浆游离型甲氧基肾上腺素类物质(metanephrines,MNs)正常者的临床特点,MNs已作为PPGL的首选检测方法在临床中广泛应用,MNs正常的PPGL较少见。方法: 选择2015年3月—2020年1月于北京大学第一医院行泌尿外科手术,病理确诊为PPGL的散发患者共104例,所有患者均有术前血浆游离型MNs检测结果,其中8例(7.69%)MNs正常。回顾MNs正常患者的就诊原因,临床表现,术前检测血浆游离型MNs、3-甲氧基酪胺(3-methoxytyramine, 3-MT)、血儿茶酚胺和嗜铬粒蛋白A(chromograninA, CgA)的结果,影像学表现,术前诊断,术前用药准备,术中血压波动情况及肿瘤组织病理学特点,并与同期MNs升高的PPGL患者相比较。对MNs正常患者进行术后随访。结果: MNs正常的8例PPGL患者中,最常见的临床症状为多汗(3/8)、腰腹痛(3/8)、头痛(2/8)、心悸(2/8)和疲乏(2/8)。对比MNs正常组和升高组患者的其他生化检验结果,血3-MT、儿茶酚胺诊断阳性率组间差异无统计学意义,血浆CgA诊断阳性率在MNs正常组显著下降(2/5 vs.41/43,P=0.005)。两组患者增强CT出现典型表现的比例差异无统计学意义。在8例MNs正常患者中,6例因明确的PPGL既往史,或典型的症状及CT表现,3-MT、CgA升高,PET-CT阳性等原因诊断为PPGL,2例误诊为无功能腺瘤或原发性醛固酮增多症。全部MNs正常患者均应用α受体阻滞剂术前准备,其中1例出现术中平均动脉压<60 mmHg。8例术后随访的中位时间为1.5(0.5~4.5)年,增强CT检查均未见新发肿瘤证据。2例MNs正常患者术后复查3-MT和(或)CgA降至正常。结论: 对于出现PPGL典型症状的肾上腺或腹膜后肿瘤患者及有PPGL既往史患者,MNs检测正常不能作为排除PPGL的充分依据。血3-MT、儿茶酚胺、CgA及影像学检查或对PPGL的诊断有帮助。怀疑MNs正常的PPGL患者推荐应用α受体阻滞剂术前准备,但应避免过量。MNs正常患者的术后随访应重点监测术前阳性的生化指标。     

血浆甲氧基肾上腺素和甲氧基去甲肾上腺素诊断嗜铬组织来源肿瘤的意义

目的探讨血浆甲氧基肾上腺素（MN）和甲氧基去甲肾上腺素（NMN）诊断嗜铬组织来源肿瘤（嗜铬细胞瘤）的意义。方法选择2003年5月—2008年12月上海交通大学医学院附属瑞金医院具有嗜铬细胞瘤筛查指征的患者,高效液相色谱分析法检测并比较嗜铬细胞瘤和非嗜铬细胞瘤患者以及嗜铬细胞患者手术前后血浆NMN和MN水平,受试者工作特征（ROC）曲线评价血浆NMN和MN诊断嗜铬细胞瘤的敏感度和特异性。结果 259例嗜铬细胞瘤患者和4387例非嗜铬细胞瘤患者入选本研究。NMN和MN的ROC曲线下面积分别为0.989±0.005和0.783±0.019;嗜铬细胞瘤与非嗜铬细胞瘤患者血浆NMN[（2930.56±4166.56）pg/mL和（70.48±25.07）pg/mL]和MN[（585.68±1368.75）pg/mL和（45.61±42.63）pg/mL]比较,差异均具有统计学意义（P=0.00）;血浆NMN在130pg/mL时诊断嗜铬细胞瘤的敏感性和特异性分别为95.4%和90.0%,血浆MN在83pg/mL时诊断敏感性和特异性分别为51.4%和90.0%。69例嗜铬细胞患者手术前后NMN[（3145.8±3651.86）pg/mL和（233.1±934.92）pg/mL]和MN[（653.7±1053.12）pg/mL和（47.56±25.82）pg/mL]比较,差异均具有统计学意义（P=0.00）。结论血浆NMN和MN水平可作为嗜铬细胞瘤的一线筛查指标,术后血浆NMN和MN水平可反映手术效果和早期发现肿瘤转移或复发。     

血浆甲氧基肾上腺素和甲氧基去甲肾上腺素诊断嗜铬组织来源肿瘤的意义

目的 探讨血浆甲氧基肾上腺素(MN)和甲氧基去甲肾上腺素(NMN)诊断嗜铬组织来源肿瘤(嗜铬细胞瘤)的意义.方法 选择2003年5月- 2008年12月上海交通大学医学院附属瑞金医院具有嗜铬细胞瘤筛查指征的患者,高效液相色谱分析法检测并比较嗜铬细胞瘤和非嗜铬细胞瘤患者以及嗜铬细胞患者手术前后血浆NMN和MN水平,受试者工作特征(ROC)曲线评价血浆NMN和MN诊断嗜铬细胞瘤的敏感度和特异性.结果 259例嗜铬细胞瘤患者和4 387例非嗜铬细胞瘤患者入选本研究.NMN和MN的 ROC曲线下面积分别为0.989±0.005和0.783±0.019;嗜铬细胞瘤与非嗜铬细胞瘤患者血浆NMN[(2930.56±4166.56) pg/mL和(70.48±25.07) pg/mL]和MN[(585.68±1368.75) pg/mL和(45.61±42.63) pg/mL]比较,差异均具有统计学意义(P=0.00);血浆NMN在130 pg/mL时诊断嗜铬细胞瘤的敏感性和特异性分别为95.4%和90.0%,血浆MN在83 pg/mL时诊断敏感性和特异性分别为51.4%和90.0%.69例嗜铬细胞患者手术前后NMN[(3 145.8±3651.86) pg/mL和(233.1±934.92) pg/mL]和MN[(653.7±1 053.12) pg/mL和(47.56±25.82) pg/mL]比较,差异均具有统计学意义(P=0.00).结论 血浆NMN和MN水平可作为嗜铬细胞瘤的一线筛查指标,术后血浆NMN和MN水平可反映手术效果和早期发现肿瘤转移或复发.     

儿茶酚胺代谢产物检测对嗜铬细胞瘤诊断价值的比较

目的比较24h尿3-甲氧基-4-羟基苦杏仁酸（VMA）,5h尿VMA／Cr,血、尿3甲氧基去甲肾上腺素（NMN）和3甲氧基肾上腺素（MN）在嗜铬细胞瘤诊断中的准确性。方法对45例嗜铬细胞瘤患者、111例肾上腺皮质腺瘤患者、145例原发性高血压患者和39例健康体检者的24h尿VMA,5h尿VMA／Cr,血、尿NMN和MN的检测结果进行比较。结果24h尿VMA检测的敏感性仅为73．3％,低于血NMN＋MN的95．6％（P〈0．05）、尿NMN＋MN的97．8％（P〈0．05）和血、尿NMN＋MN联合检测的100％（P〈0．01）。5h尿VMA／Cr检测的特异性为84．1％,低于24h尿VMA的92．2％、血NMN＋MN的93．6％、尿NMN＋MN的93．9％和血、尿NMN＋MN的联合检测99．7％（P均〈0．01）：24h尿VMA、5h尿VM～Cr、血NMN＋MN和尿NMN＋MN的ROC曲线下面积分别为0．884、0．923、0．972和0．985。结论血、尿NMN＋MN检测的敏感性和特异性高,是临床诊断嗜铬细胞瘤较为理想的检测方法。如果两者联合检测将进一步提高诊断的准确性。     

嗜铬细胞瘤及副神经节瘤不同生化表型的CT征象对比研究

目的 分析生化阴性嗜铬细胞瘤及副神经节瘤（pheochromocytomas and paragangliomas,PPGLs）的电子计算机断层扫描（computed tomography,CT）征象是否有别于生化阳性PPGLs,同时了解生化阳性PPGLs不同表型的CT征象是否存在差异。方法 回顾性分析131例PPGLs患者的术前腹部增强CT图像,包括肿瘤位置、大小、形态、囊变坏死、液-液分层、钙化、向心结节状强化、肿瘤内粗大血管、强化包膜、绝对廓清率及相对廓清率。根据生化水平,将患者分为生化阳性组和阴性组,阳性组进一步分为去甲肾上腺素型、肾上腺素型及多巴胺型。比较各组及各表型间的CT征象差异。结果 相较于生化阴性组,阳性组PPGLs更大（Z=-2.064,P=0.039）、囊变坏死（χ²=6.610,P=0.010）及向心结节状强化（χ²=3.909,P=0.048）的比例更高;相较于去甲肾上腺素型,肾上腺素型PPGLs更大（Z=-2.036,P=0.042）、强化包膜比例更高（χ²=7.242,P=0.007）。结论 肿瘤大小、囊变坏死及向心结节状强化的CT征象有助于术前诊断生化阴性PPGLs,肿瘤大小及强化包膜有助于解释去甲肾上腺素型及肾上腺素型PPGLs不同临床表现产生的机制。     

毛细管电泳检测尿儿茶酚胺代谢产物及在诊断嗜铬细胞瘤中的应用

目的 探讨毛细管电泳法检测尿儿茶酚胺代谢产物对嗜铬细胞瘤的诊断意义.方法 采用毛细管电泳技术检测46例正常人及11例嗜铬细胞瘤患者尿中去甲变肾上腺素(normetanephrine, NMN)、间甲肾上腺素(metanephrine, MN)和3-甲氧基-4羟基苦杏仁酸(vanillylmandelic acid, VMA)含量.结果 嗜铬细胞瘤患者与正常人比较NMN和MN有统计学意义(P<0.05);VMA无统计学意义(P>0.05);NMN和MN联合检测阳性率为100%,假阳性率为19.56%;NMN和VMA联合检测阳性率为100%,假阳性率为10.87%. 结论毛细管电泳法对NMN和VMA联合检测对于诊断嗜铬细胞瘤有意义.     

肾上腺外嗜铬细胞瘤的诊断

为提高肾上腺外嗜铬细胞瘤的术前诊断率，作者对30例经手术病理学证实的肾上腺外嗜铬细胞瘤的临床资料作回顾性分析。本组肿瘤位于腹主动脉旁15例、膀胱10例、肾门4例、纵隔1例。术前23例行24h尿VMA测定（15～98mg）均高于正常值；20例行B超均获正确定位；10例行CT扫描，6例获正确定位；10例行膀胱镜检查，1例肿块呈球状元蒂，9例呈菜花样带蒂。提示：术前行24hVMA测定对该病的定性诊断有重要意义；定位诊断首选B超。     

异位嗜铬细胞瘤的临床及MSCT诊断

目的 探讨异位嗜铬细胞瘤的CT和临床特征. 方法 结合文献,回顾性分析有完整病史资料及手术病理结果的21例异位嗜铬细胞瘤的CT表现.结果 良性者20例,边界清晰;恶性者1例,边界不清或清楚.肿瘤在CT上表现为圆形、椭圆形肿块;平扫有16例呈等密度实性肿块,5例瘤体平扫密度不均,呈等、低、混杂密度,其内有大小不等的中心性或不规则液化、坏死、囊变区.经增强后扫描肿瘤实性部分尤其是周边部分强化明显而持续,且门脉期多数仍呈持续强化,而坏死区无强化.结论 结合临床资料,行搜索性CT平扫、增强扫描对异位嗜铬细胞瘤的定位及定性诊断起关键的作用.     

嗜铬细胞瘤的临床诊治规范进展

2004年,世界卫生组织(WHO)将嗜铬细胞瘤定义为起源于肾上腺产生儿茶酚胺的嗜铬细胞的肿瘤.     

Differential diagnosis and laparoscopic treatment of adrenal pheochromocytoma and ganglioneuroma

Background Adrenal ganglioneuroma is a rare adrenal pathogenic disease with difficult differential diagnosis from adrenal pheochromocytoma. Currently, very limited literature is available to allow a differential diagnosis of these two conditions from each other. This study aimed to evaluate the clinical profile, differential diagnosis and surgical treatments of both conditions. Methods Clinical characteristics of 36 patients with adrenal pheocheomocytoma and 18 patients with adrenal ganglioneuroma were analyzed. Data from CT scans and surgical treatments from 1999 to 2007 were collected. Endocrine hormone tests and ^131I-metaiodobenzylguanidine （MIBG） were performed. Neither ^131I-MIBG nor endocrine hormone tests were available in 9 cases of asymptomatic adrenal ganglioneuroma with tumor size less than 4 cm and there were negative findings from contrast enhanced CT scans. The level of urine catecholamine of patients was compared by one-way analysis of variance. Results The mean age of patients in the adrenal ganglioneuroma group was 41.2 years （16-67 year） and in the adrenal pheochromocytoma patients 38 years （17-74 year）. Contrast enhanced CT showed that the foci were intensified in 5 cases （27.8%） of adrenal ganglioneuroma and there were obvious contrast indications in 30 （83.3%） of the pheochromocytoma. Catecholamine levels in a 24-hour urine sample were normal in 4 patients with adrenal ganglioneuroma and increased in 36 （100%） cases with adrenal pheochromocytoma. ^131I-MIBG nuclear scan showed negative results in 4 patients （100%） with adrenal ganglioneuroma and positive results in 25 （96.2%） with adrenal pheochromocytom. Laparoscopy for adrenal tumors was performed through a transperitoneal or retroperitoneal approach during a follow-up period of （43±6） months, and all cases survived well. Conclusions CT, urinary catecholamine and ^131I-MIBG are standard and efficient tools for differential diagnosis of adrenal ganglioneuroma from pheochromocytoma. Laparoscopic surgery can be performed through a transperitoneal or retroperitoneal approach depending on the finding of CT scans. Open surgery is necessary for patients with blood loss of more than 800 ml and violent fluctuation of intraoperative blood pressure.     

Plasma levels of tissue inhibitor of matrix metalloproteinase-1 correlate with diagnosis and prognosis of glioma patients

Background There is no validated blood biomarker available for glioma management. Invasive growth is the key feature of glioma. We assessed the clinical usefulness of plasma tissue inhibitor of metalloproteinase 1 （TIMP-1）, which has less molecular weight than metalloproteinases, as a potential blood biomarker for glioma. Methods A total of 285 patients and 59 normal subjects were studied. Plasma concentration of TIMP-1 was measured with enzyme-linked immunosorbent assay. Plasma TIMP-1 was compared between normal and glioma patients, between patients with different pathological grades, and between patients with different prognoses. Longitudinal changes in plasma TIMP-1 during treatment were also evaluated. Plasma matrix metalloproteinase （MMP）-9 level was also assayed and its clinical usefulness was compared with that of TIMP-1. Results Plasma TIMP-1 and MMP-9 were both increased in glioma patients compared with normal controls （TIMP-1： P 〈0.001; MMP-9： P=0.007）. Plasma TIMP-1 increases with increased tumor grade. In Grade Ⅳ gliomas, plasma TIMP- 1 significantly increased after ＂successful removal＂ of the tumor （paired samples t-test, before operation vs. during chemotherapy without recurrence, t = -2.131, P=0.038）, but did not change significantly at the time of tumor recurrence （during chemotherapy without recurrence vs. after tumor recurrence, t = -0.652, P=-0.632）. High plasma TIMP-1 level correlated with better survival in Grade IV glioma patients （hazard ratio： 0.550, 95% CI： 0.101-1.000, P=0.036）. In Grade IV gliomas, patients with higher plasma TIMP-1 had significantly longer survival time than those with lower plasma TIMP-1 level （25.23 vs. 18.95 months, log-rank P=0.045）. Plasma MMP-9 did not show significant association with either the pathological grade or the prognosis of glioma patients. Conclusions Plasma TIMP-1 is associated with the diagnosis and prognosis of glioma patients. It appears to have better usefulness for guiding clinical decision making than plasma MMP-9. Further studies in an expanded patient population are needed to better define its clinical usefulness.