肾上腺皮质肿瘤的DNA含量测定及临床意义

应用细胞分光光度计测定肾上腺皮质细胞核DNA含量,旨在揭示正常肾上腺皮质、肾上腺皮质增生、腺瘤和癌的细胞核DNA定量差异,探讨其对肾上腺皮质肿瘤的诊断价值和判断预后的意义。 一、材料与方法 1.实验材料 选择本校西南医院和新桥医院1980～1992年手术切除的54例肾上腺皮质肿瘤和增生档案资料,并进行随访观察,平均随访时间约4年5个月（8个月～11年）。分为以下四组。     

肾上腺皮质肿瘤中NF-κB的表达及意义

目的探讨NF-κB在肾上腺皮质肿瘤中的表达及其临床意义。方法用免疫组化法检测肾上腺疾病标本(肾上腺皮质癌15例,肾上腺皮质瘤30例,肾上腺皮质增生11例,正常肾上腺皮质组织7例)中NF-κB的表达。结果 NF-κB在肾上腺皮质癌组中阳性表达为9/15例,其中2例(+++),4例(++),3例(+),6例(-);在肾上腺皮质瘤组中,NF-κB阳性表达8/30例,其中0例(+++),2例(++),6例(+),22例(-);增生组有2例阳性,均为(+);在正常组中未检测出阳性。在肾上腺皮质癌组中的表达明显高于在其他组中的表达,肾上腺皮质癌组与肾上腺皮质瘤组相比较,差异有统计学意义(P0.01)。结论 NF-κB对肾上腺皮质癌的诊断具有重要意义。     

肾上腺皮质癌的药物治疗进展

肾上腺皮质癌(ACC)是一种预后差的少见病,患者常表现为类固醇激素过多症(如库欣综合征、原发性醛固酮增多症或性征异常)或腹部肿块.在有内分泌功能的患者中,以库欣综合征表现最为常见.米托坦是治疗ACC最重要的药物,可作为手术后的辅助治疗药物,在晚期ACC患者中,米托坦可联合依托泊苷、阿霉素、顺铂联合米托坦或者链脲佐菌素联合米托坦进行治疗.药物靶向治疗,如胰岛素样生长因子Ⅰ(IGF-Ⅰ)受体抑制剂、酪氨酸激酶抑制剂(舒尼替尼,索拉非尼等)可能带来新的治疗前景.

Abstract：

Adrenocortical carcinoma (ACC) is a rare disease with poor prognosis.Patients usually present with signs of steroid hormone excess (e.g.Cushing's syndrome, Conn's syndrome, virilization) or an abdominal mass.In functional cases, Cushing's syndrome is the most frequent presentation.Mitotane is still the most important single drug for ACC treatment, and it plays a role in adjuvant therapy postoperatively as well as in advanced disease.In advanced ACC, a combination of mitotane with etoposide, doxorubicin, cisplatin or streptozotocin with mitotane may be used.Targeted therapies, such as insulin-like growth factor Ⅰ (IGF- Ⅰ)receptor inhibitor and multiple kinase inhibitors like sunitinib and sorafenib hold great promises.     

Ki-67和P21在肾上腺皮质癌中的表达及意义

目的　探讨肾上腺皮质癌 (ACC)中Ki 67和P2 1的表达及其意义。方法　采用免疫组化SP法和图像分析技术对 8例正常肾上腺组织、2 0例肾上腺腺瘤 (ACA)、19例肾上腺皮质癌中Ki 67、P2 1进行检测。结果　Ki 67和P2 1的表达在肾上腺腺瘤与肾上腺皮质癌间差异均有统计学意义 (P <0 .0 1,P <0 .0 5 )。Ki 67的表达与肾上腺皮质癌分期、浸润或转移、2年生存情况相关(P <0 .0 1) ,与肿瘤大小无关 (P >0 .0 5 )。P2 1的表达与肾上腺皮质癌的大小、分期、浸润或转移、2年生存情况均无显著相关 (P >0 .0 5 )。结论　Ki 67和P2 1对肾上腺皮质良恶性肿瘤具有重要的鉴别诊断作用 ,Ki 67可作为判断肾上腺皮质癌预后不良的指标。     

肾上腺皮质腺癌的诊断与治疗

目的 总结肾上腺皮质腺癌（ACC）的诊治经验,提高肾上腺皮质癌的诊治水平.方法 对5例ACC患者的临床表现、实验室及影像学检查、治疗和预后进行回顾性分析.结果 本组B超示肾上腺实质性中等回声,内部回声不均匀,可见点状血流反射;CT均示肿瘤边缘模糊,CT值32 ～ 65 HU,强化不均匀;MRI示肿瘤边界欠清,T2加权片上2例呈高信号,1例呈高低混杂信号,病灶中心坏死区无明显强化.5例均行开放性手术完全切除肿物,术后应用米托坦2例、放疗1例;术后随访6 ～ 36个月,平均生存23个月.结论 B超、CT等检查有利于ACC的早期诊断,手术切除是治疗ACC的有效方法.     

肾上腺皮质癌临床与基础研究

<正>肾上腺皮质癌是一类进展迅速的罕见内分泌恶性肿瘤,年发病率(0.7～2.0)例/百万人,发病年龄呈双峰分布,好发于5岁以下儿童及40～50岁成人,女性发病率略高于男性(1.2∶1)^[1-3]。随着影像学检测技术普及,肾上腺肿瘤检出率呈上升趋势。但目前仍缺乏有效鉴别良、恶性肾上腺肿瘤的方法,肾上腺皮质癌确诊依赖于病理诊断,其中Weiss评分在临床应用最广泛,但评分标准受主观因素影响,敏感性和特异性都存在一定缺陷。为简化病理诊断流程、提升诊断准确性^[4],越来越多的学者关注于肾上腺皮质癌的分子生物学研究,以期协助临床诊断和探索新的靶向治疗药物。     

18例肾上腺皮质嗜酸细胞腺瘤患者的临床特征

目的 探讨肾上腺皮质嗜酸细胞腺瘤临床特点,以提高临床认识.方法 回顾性分析本院1993年1月至2009年11月住院的586例肾上腺皮质腺瘤中术后病理证实为肾上腺皮质嗜酸细胞腺瘤的患者18例(男性7例,女性11例),年龄(45.5±15.9)岁,病程(13.3±13.1)个月.结果 18例肾上腺皮质嗜酸细胞腺瘤患者中皮质醇增多症6例,原发性醛固酮增多症2例,皮质醇增多症合并原发性醛固酮增多症1例,无功能瘤9例.术前误诊为嗜铬细胞瘤4例.18例患者均经肾上腺超声诊断,均行手术治疗,其中腹腔镜手术13例,开腹手术5例,左侧11例,右侧7例,肿瘤平均直径5.6 cm.术后病理支持肾上腺皮质嗜酸细胞腺瘤,其中存在恶性倾向5例,恶性1例,良性12例.随访11例,随访时间(20.5±20.1)个月,死亡2例,存活9例,复发1例.结论 肾上腺皮质嗜酸细胞腺瘤是一病理诊断,临床表现多样,肿物体积多较大,多数可行超声检查发现,但易被误诊.与以往报道不同,本组病例以内分泌功能异常居多.该病多数为良性,但恶性倾向明显,需密切随访.

Abstract：

Objective To explore the clinical features of adrenocortical oncocytoma for better understanding. Methods A total of 586 patients with adrenal cortical adenoma were retrospectively analyzed in our hospital from January 1993 to November 2009, in which 18 were diagnosed as adrenal cortical oncocytoma pathologically, with 7 male and 11 female, aged ( 45.5 ± 15.9 ) years, and the disease course of( 13.3 ± 13.1 )months. Results 6 patients suffered from Cushing's syndrome, 2 primary hyperaldosteronism, 1 had clinical features of both Cushing's syndrome and primary hyperaldosteronism, and 9 were nonfunctional. 4 cases were misdiagnosed as pheochromocytoma preoperatively. All 18 patients were diagnosed by B-mode ultrasound and operation ( 13 by laparoscopy, 5 by laparotomy). 11 tumors were located in the left adrenal while 7 in the right, with the average tumor size of 5.6 cm in diameter. Histopathologically, 1 was oncocytic adrenocortical carcinoma, while 17 were adrenocortical oncocytoma, in which 5 were potentially malignant and 12 were benign. 11 patients were followed up for 20.5±20.1 months. 2 patients were dead, and 9 were alive with tumor recurrence in 1 case. Conclusions Adrenocortical oncocytoma is a pathological diagnosis and the clinical manifestations are various. The tumors are usually large in size, and can easily be found by ultrasound, but may be wrongly diagnosed as pheochromocytoma. Being different from previous reports, the majority of these patients present with endocrine dysfunction. Most of these cases are benign, but malignant potential is obvious. Therefore,follow-up is very important.     

miR-214在肾上腺皮质肿瘤组织中的表达及意义

目的探讨miR-214在肾上腺皮质肿瘤组织中的表达及意义。方法选择21例行肾上腺皮质肿瘤手术患者的术后切除组织,其中肾上腺皮质腺瘤组织8份,其瘤旁正常组织8份,肾上腺皮质癌组织5份;另选人肾上腺皮质癌SW-13细胞系(SW-13细胞系)和裸鼠皮下移植瘤组织6份。采用RT-PCR技术检测各组织中的miR-214表达。结果与肾上腺皮质腺瘤组织和瘤旁正常组织比较,肾上腺皮质癌组织、SW-13细胞系、裸鼠皮下移植瘤组织中的MiR-214表达明显降低(P均<0.01);与肾上腺皮质癌组织和SW-13细胞系比较,裸鼠皮下移植瘤组织中的MiR-214表达降低(P<0.05)。结论 miR-214表达下调可能参与肾上腺皮质癌的发生、发展,深入探讨其功能和作用机制有重要意义。     

早期肺鳞癌相关蛋白的筛选及其表达验证

目的应用蛋白质组学技术筛选早期肺癌癌变相关蛋白。方法利用双向凝胶电泳方法分离人早期肺鳞癌组织和相应癌旁正常组织总蛋白,选择差异蛋白质点进行质谱分析。免疫组织化学法验证部分差异蛋白质的表达差异。结果用DeCyder软件DIA模块分析显示,每块2-DE胶分离近1470左右个蛋白质点,再经过BVA模块分析,找出在9张图像中均出现,差异有统计学意义(P0.05)、两组间蛋白含量比值在1.5倍以上的差异性蛋白质点24个,成功鉴定14个。选择在癌组织中高表达的差异蛋白点进行质谱分析,最终鉴定为AnnexinⅡ、Cathcpsin D等蛋白质。免疫组织化学检测结果显示,AnnexinⅡ、Cathcpsin D蛋白在肺鳞癌组织中的阳性表达率均显著增高(P0.05)。结论蛋白质组学方法是一种应用于初步筛选早期肺癌相关蛋白的有效方法 ,所鉴定的蛋白为进一步筛选用于肺癌早期诊断及其治疗的分子标志物奠定了前期基础。     

阿霉素干预与肾上腺皮质癌干细胞标志物的表达

目的 探讨阿霉素(ADM)干预下人肾上腺皮质癌裸鼠模型干细胞标志CD133、ABCG2的表达及意义.方法 SW-13细胞系建立裸鼠皮下移植瘤模型,ADM体内干预后原代培养获得ADM组细胞株,未予干预直接原代培养获得对照组细胞株.用单细胞成克隆技术检测细胞的增殖能力,免疫组化法和流式细胞法检测肿瘤干细胞标志物CD133、ABCG2的表达.结果 ADM组细胞株的克隆形成率高于对照组(P＜0.05);流式细胞法和免疫组化法提示ABCG2在两组细胞中均有阳性表达,ADM组细胞株的流式细胞表达率高于对照组细胞株(P＜0.05);以上两种方法均表明CD133在两组中阴性表达.结论 ADM组细胞具有一定的肿瘤干细胞特征,ABCG2参与肾上腺皮质癌细胞耐药机制,可能为分子靶向治疗的潜在靶点.     

Ectopic adrenal cortical adenoma in the gastric wall:Case report

Ectopic adrenal cortical neoplasms are extremely rare. Ectopic adrenocortical tissue can be found in locations such as the celiac axis,the broad ligament,the adnexa of the testes,and the spermatic cord;however,they rarely involve the stomach.We report an unusual case of a patient with an ectopic adrenal cortical adenoma in the gastric wall.The patient was a 72-year old female admitted to our hospital with upper abdominal discomfort.Physical examination revealed tenderness below the xiphoid process.Both computed tomography and fibergastroscopy revealed a mass on the lesser curvature side of the gastric antrum;it was initially diagnosed as a gastric stromal tumor.After adequate preparation,the patient underwent surgery.During the procedure,we found a 30 mm×30 mm mass with medium density in the lesser curvature near the gastric antrum within the serosa.Following immunohistochemistry examination, we corrected the diagnosis to an ectopic adrenal cortical adenoma;the tumor was nonfunctional.     

Molecular profiling of hepatocellular carcinomas by cDNA microarray

Hepatocellular carcinoma (HCC) is one of the most common cancers in the world. Conventional diagnosis and treatment of this malignancy have been dismal and should be complemented by novel tools. The development and progress of HCC are believed to be caused by the accumulation of genetic changes resulting in altered expression of thousands of cancer-related genes, which can be measured by globe genetic analysis. Gene expression profiling of HCC has been employed to elucidate hepatocarcinogenesis and disclose molecular mechanisms underlying complex clinical features. Identifying phenotype-associated genes/profiles has impacts on current diagnosis and management strategy of HCC. In spite of some pitfalls of this technology and challenges in improving the research process, scrutinous validation of profiling data of HCC combined with other approaches will eventually benefit the patients.     

肾上腺肿瘤45例临床分析

目的　探讨肾上腺肿瘤的临床特点和检查方法 ,提高术前诊断水平。方法　对 4 5例肾上腺肿瘤及增生的临床表现、激素水平、CT定位诊断及术后病理进行回顾性分析。结果　 4 5例中醛固酮瘤 15例 ,误诊的双侧肾上腺增生 3例 ,嗜铬细胞瘤 8例 ,腺瘤、腺癌型皮质醇增多症 4例和意外瘤 15例。结论　术前肿瘤性质及内分泌功能检查有利于术前准备、术中处理及术后并发症预防     

Detection of adrenal veins on selective retrograde CT adrenal venography in comparison with digital subtraction angiography in subjects with established diagnosis of one-sided adrenal aldosterone-producing tumor confirmed by adrenal vein sampling,histopathology and clinical course

Purpose

Adrenal vein (AV) sampling (AVS) is the diagnostic gold standard for primary aldosteronism (PA), but right-sided AVS is difficult. We compared detection of AVs by selective retrograde CT adrenal venography (SRCTAV) with digital subtraction angiography (DSA).

Materials and methods

Data on 29 subjects (11 males, mean age 55 y) with increased serum aldosterone concentrations (SAC) and a diagnosed right or left aldosterone-producing tumor (APT) by AVS who underwent laparoscopic adrenalectomy were retrospectively analyzed. Before AVS, visualizing AVs was attempted by DSA and SRCTAV (Aquilion). If after the adrenocorticotropic hormone loading test serum cortisol concentration (SCC) from either AV was > 200 μg/dl, AVS was considered successful. If the SAC/SCC ratio for one side was ≥ 4 times higher than the other side, we diagnosed a one-sided APT.

Results

Left and right AV, respectively, were visualized in 29 (100%) and 22 subjects (76%) by DSA and 29 (100%) and 28 subjects (97%) by SRCTAV, with right-AV detection significantly higher by SRCTAV (p < 0.05). Cannulations were regarded successful in 28 subjects having both AVs observed on SRCTAV but not in the remaining subject whose adrenocortical scintigram was positive, however. Adrenalectomy was performed with a diagnosis of adenoma. Among 28 subjects with successful AVS, histopathological diagnoses included adenoma (25), nodular hyperplasia (2) and normal (1). After adrenalectomy, antihypertensive drug usage in 28 patients was reduced or stopped with decreases in SAC (97%).

Conclusions

Detection of AV was significantly higher by SRCTAV than DSA, especially on the right side, in 29 subjects diagnosed with one-sided APT.     

肾上腺巨大肿瘤误诊为肝癌1例报告及文献回顾

1病例资料患者男性,45岁,1年前无明显诱因出现上腹部胀痛不适,进食后加重,且伴有腰背部放射痛,自行口服止痛药物缓解。1周前疼痛加重,行腹部彩超发现肝脏占位性病变,就诊于当地医院,查腹部增强CT考虑为肝脏占位性病变,患者为求进一步诊断及治疗入我院就诊。查体:全身皮肤、巩膜无黄染,腹部平坦,未见胃肠型及蠕动波。全腹软,无压痛、反跳痛及肌紧     

Classification of adrenal cortical tumors: promise of the 'molecular' approach

Surgical pathologists, using routine histological techniques and tumor morphology, have established the overall taxonomy of adrenal cortical tumors that dictates care of patients with these tumors. However, a novel molecular classification of these tumors would provide numerous benefits to clinicians and patients, including a more accurate classification of diagnostically intermediate tumors, separation of carcinomas into prognostically-relevant subgroups, and optimal selection of therapy. Recent advances towards a molecular classification of adrenal cortical tumors are presented and discussed.     

Proteomic mapping in live Drosophila tissues using an engineered ascorbate peroxidase

Characterization of the proteome of organelles and subcellular domains is essential for understanding cellular organization and identifying protein complexes as well as networks of protein interactions. We established a proteomic mapping platform in live Drosophila tissues using an engineered ascorbate peroxidase (APEX). Upon activation, the APEX enzyme catalyzes the biotinylation of neighboring endogenous proteins that can then be isolated and identified by mass spectrometry. We demonstrate that APEX labeling functions effectively in multiple fly tissues for different subcellular compartments and maps the mitochondrial matrix proteome of Drosophila muscle to demonstrate the power of APEX for characterizing subcellular proteomes in live cells. Further, we generate “MitoMax,” a database that provides an inventory of Drosophila mitochondrial proteins with subcompartmental annotation. Altogether, APEX labeling in live Drosophila tissues provides an opportunity to characterize the organelle proteome of specific cell types in different physiological conditions.Specialized biological processes are carried out in specific organelles and subcellular compartments. For example, mitochondria are the site of oxidative respiration, neurons pass electrical or chemical signals to others through synapses, and apical and basolateral domains of epithelial cells are critical for their polarized functions. Understanding how these structures underlie specialized functions requires the comprehensive identification of proteins within spatially defined cellular domains.A common strategy to study the localization of a particular protein is to generate green fluorescent protein (GFP) fusion proteins. However, it is time-consuming and labor-intensive to investigate protein localization at a large scale using GFP tagging, especially in vivo. Therefore, highly sensitive mass spectrometry (MS) approaches have been developed to systematically characterize the proteome of subcellular compartments. However, using MS approaches to characterize the proteome of subcellular domains has been limited by purification methods and is commonly associated with numerous false positives and false negatives due to contamination and loss of components during purification, respectively. For example, mitochondria are composed of an outer membrane and an inner membrane, generating two subcompartmental regions: the intermembrane space and the matrix located within the inner membrane. Because the ultrastructure of mitochondria is often disrupted during isolation processes, the isolation of specific subcompartmental regions of mitochondria is prone to contamination.Recently, a method based on an engineered ascorbate peroxidase (APEX) has been developed and shown to function in cultured mammalian cells for proteomic mapping (1). Upon activation, the APEX enzyme turns a biotin-phenol substrate into a highly reactive radical that covalently tags neighboring proteins on electron-rich amino acids such as tyrosine. Biotinylated endogenous proteins can then be isolated and identified by MS. Thus, APEX labeling can be applied to bypass organelle purification steps, offering an alternative approach for systematic proteomic characterization in live cells. Here we report that the approach can be applied to characterize the subcellular proteome in live tissues and map the mitochondrial matrix proteome of Drosophila muscle. In addition to characterizing a number of uncharacterized putative mitochondrial proteins, we establish MitoMax, a database that provides an inventory of Drosophila mitochondrial proteins with subcompartmental annotation.     

经腹腹腔镜肾上腺嗜铬细胞瘤切除术(附15例报告)

目的观察经腹腹腔镜肾上腺嗜铬细胞瘤切除术治疗肾上腺嗜铬细胞瘤的疗效。方法用经腹腹腔镜手术治疗肾上腺嗜铬细胞瘤15例。结果手术均成功。手术时间50-160 min,术中出血量40-220 ml。12例随访5-36个月,10例患者血压恢复正常,2例血压明显下降,均无局部复发。结论经腹腔腹腔镜肾上腺嗜铬细胞瘤切除术术中解剖标志清楚,手术安全性高,效果满意,可作为肾上腺嗜铬细胞瘤首选治疗方法。