促泌素在胃肠道神经内分泌肿瘤中的表达及其临床意义

目的 比较促泌素(secretagogin,SCGN)与传统的神经内分泌标记物在胃肠道神经内分泌肿瘤中的表达差异.方法 收集胃肠道手术标本共88例,其中实验组为8例类癌和20例非典型类癌,对照组为40例腺癌伴神经内分泌分化和20例腺癌.所有标本均使用SCGN、PGP9.5、CD56、NSE、Syn及CgA进行免疫组织化学SP两步法染色.结果 SCGN可在胃肠道粘膜同有层腺体的弥散性神经内分泌细胞中表达,多显示“开放型”的神经内分泌细胞.除CD56和NSE各在1例胃肠道腺癌中阳性表达外,SCGN及其它标记物在20例腺癌中均无表达,所有标记物之间均无统计学差异(P＞0.05).SCGN在40例胃肠道腺癌伴神经内分泌分化、20例非典型类癌和8例类癌巾的阳性表达率均最高,分别为62.5％ (25/40)、90％(18/20)和100％(8/8),PGP9.5阳性表达率均最低分别为32.5％(13/40)、45％ (9/20)和37.5％(3/8),两标记物在这三组肿瘤中的表达均有显著统计学差异(P＜0.01),而CD56、NSE、Syn和CgA在以上三组肿瘤中的表达率均较高,与SCGN比较均无统计学差异(P＞0.05).所有标记物在腺癌伴神经内分泌分化、非典型类癌和类癌中的阳性表达率均明显高于腺癌(P＜0.01);SCGN、Syn和CgA在非典型类癌和类癌巾的阳性表达均高于腺癌伴神经内分泌分化(P＜0.05);所有标记物在非典型类癌和类癌之间的阳性表达率均无统计学差异(P＞0.05).结论 SCGN作为一种新型的神经内分泌标记物与传统标记物Syn和CgA联合,可应用于胃肠道神经内分泌肿瘤的临床病理诊断.     

肾上腺皮质嗜酸细胞腺瘤临床病理观察

目的探讨肾上腺皮质嗜酸细胞腺瘤的临床病理特征和诊断要点。方法分析8例肾上腺皮质嗜酸细胞腺瘤的临床资料,观察其组织学形态及免疫表型特征,并复习相关文献。结果 8例患者,3名女性5名男性,6例患者均为体检时偶然发现,无明显临床症状,肾上腺占位术后标本病理检查结果示:镜下肿瘤细胞边界清楚,有明显的包膜,排列呈巢状、梁状或腺泡状,周围包绕纤细的血窦样毛细血管网。肿瘤间质内可见少量成熟淋巴细胞浸润。肿瘤细胞由明显胞浆嗜酸性的大细胞组成,少数肿瘤细胞局部胞浆透亮,富含脂质,有时可见嗜酸性核内假包涵体和脂褐素。局部区域偶见怪异核细胞,核分裂罕见。免疫组织化学表型:CD56及Syn、MelanA、α-inhibin阳性,PCK灶状阳性,CgA、S-100阴性,Ki67增殖指数约为2%;特殊染色:网状纤维染色示肿瘤细胞巢状结构存在。结论肾上腺皮质嗜酸细胞瘤是一种罕见的肾上腺皮质良性肿瘤,大多数表现为无功能的腺瘤。手术切除仍然是主要的治疗方法。这种疾病可以作为良性肿瘤来治疗,SS预后尚可。     

胃异型增生上皮和胃腺癌神经内分泌分化的检测

目的检测胃异型增生上皮及胃腺癌组织中神经内分泌的表达.方法应用免疫组织化学法检测10例正常胃粘膜、63例癌旁低度异型增生、26例高度异型增生及相应胃腺癌组织中嗜铬粒蛋白A(CgA)、突触素(Syn)和神经元特异性烯醇化酶(NSE)表达结果 CgA、Syn和NSE在癌旁低度异型增生、高度异型增生及相应胃腺癌组织中阳性表达率有显著性差异(P<0.01).结论胃异型增生上皮和胃腺癌伴神经内分泌是一种常见的现象,它反映了胃腺癌发生发展的多步骤过程.     

尿甲氧基肾上腺素及甲氧基去甲肾上腺素在嗜铬细胞瘤诊断中的作用

目的:测定尿液中甲氧基肾上腺素和甲氧基去甲肾上腺素,并评价其在嗜铬细胞瘤诊断中的作用。方法:选择酶联免疫分析法,对2014年1月至2015年1月广州军区广州总医院有嗜铬细胞瘤筛查指征的患者的24 h尿甲氧基肾上腺素和甲氧基去甲肾上腺素进行测定。结果:嗜铬细胞瘤患者24 h尿甲氧基肾上腺素和甲氧基去甲肾上腺素含量明显高于肾上腺皮质腺瘤、肾上腺增生、原发性醛固酮增多症等其他肾上腺占位性疾病患者,同时也显著高于原发性高血压患者及健康人参考区间上限值;以甲氧基去甲肾上腺素806.5μg或甲氧基肾上腺素385.5μg为切点,诊断嗜铬细胞瘤的敏感度为83.3%、特异性为90%;甲氧基去甲肾上腺素和甲氧基肾上腺素的受试者工作特征曲线下面积分别为0.912±0.057和0.886±0.076。结论:酶联免疫法检测24 h尿甲氧基去甲肾上腺素和甲氧基肾上腺素的方法准确度和特异性均较高,可以作为嗜铬细胞瘤的初步筛查、排除、临床诊断的可靠的实验室检查方法。     

胎儿胰腺发育中CgA和NSE的表达及其意义

目的检测人胎儿胰腺中CgA和NSE的表达特征,初步探讨胎儿胰腺发育过程弥散神经内分泌系统的形成及其生物学作用.方法用免疫组织化学SP法,检测嗜铬素A(chromograin A,CgA)和神经元特异性烯醇化酶(neuron specific enolase,NSE)在不同胎龄胎儿胰腺组织中的表达.结果CgA在16-38周的胰腺中均有表达,随胎儿发育,CgA阳性细胞分布状态和反应程度均有差异变化;NSE在22-38周胎儿胰腺中表达,集中定位于胰腺的内分泌部细胞.结论CgA和NSE在人胎儿胰腺中的阳性表达,反映出弥散神经内分泌系统在胎儿胰腺中的形成过程;表明胎儿胰岛的形成及其DNES细胞的分泌,有调节胰腺外分泌部发育分化的作用,也提示胰岛DNES细胞通过调节血糖可能对胎儿个体发育具有重要影响.     

心肌酶谱、动态心电图及冠状动脉CT血管造影诊断嗜铬细胞瘤儿茶酚胺性心脏损害价值研究

摘要 目的：探讨心肌酶谱、动态心电图及冠状动脉CT血管造影诊断嗜铬细胞瘤儿茶酚胺性心脏损害的临床价值。方法：收集2013年1月-2020年4月在我院诊断为嗜铬细胞瘤患者114例,其中嗜铬细胞瘤儿茶酚胺性心脏损害的患者27例。所有患者均完善术前常规检查（血常规、胸片、动态心电图）、心肌酶谱、心脏超声、冠状动脉CTA等临床资料,并收集患者一般临床资料,如血压、临床症状等。结果：114例嗜铬细胞瘤患者中,27例患者存在嗜铬细胞瘤儿茶酚胺性心脏损害。嗜铬细胞瘤儿茶酚胺性心脏损害患者一般临床资料与嗜铬细胞瘤无儿茶酚胺性心脏损害的患者差异无统计学意义（P＞0.05）。嗜铬细胞瘤儿茶酚胺性心脏损害以高血压为主要表现,临床症状表现多样,可伴有头痛、心悸、多汗三联征表现。114例患者中,26例患者出现心肌酶谱升高,36例患者存在不同程度的心电图异常、24例患者冠状动脉CTA异常,嗜铬细胞瘤儿茶酚胺性心脏损害患者在心肌酶谱、动态心电图及冠状动脉CTA异常例数与嗜铬细胞瘤无儿茶酚胺性心脏损害患者中差异均有统计学意义（P＜0.05）。114例患者中心肌酶谱或心电图或冠状动脉CTA异常的患者总共56例,其中嗜铬细胞瘤儿茶酚胺性心脏损害患者23例,嗜铬细胞瘤无儿茶酚胺性心脏损害患者有33例,差异有统计学意义（P＜0.05）。嗜铬细胞瘤儿茶酚胺性心脏损害患者中,心律失常最为常见。结论：嗜铬细胞瘤儿茶酚胺性心脏损害患者心肌酶谱、动态心电图及冠状动脉CTA均可存在异常表现,但特异性、敏感性不高,三者同时综合分析可以提高临床诊断。     

尿去甲基肾上腺素/甲氧基肾上腺素测定对嗜铬细胞瘤的方法学比较

目的:通过对尿儿茶酚胺代谢产物去甲肾上腺素、甲氧基肾上腺素的测定,综合分析其对嗜铬细胞瘤的早期临床诊断价值。方法:利用酶联免疫分析法和传统柱层析法,对正常人和临床诊断为嗜铬细胞瘤及肾上腺占位病变并伴有阵发性高血压患者的24h尿去甲基肾上腺素/甲氧基肾上腺素和3-甲氧基-4-羟基苦杏仁酸(VMA)进行测定。结果:与VMA相比,24h尿去甲基肾上腺素/甲氧基肾上腺素在嗜铬细胞瘤患者中的测定值要显著高于其他肾上腺占位性病变伴高血压患者和正常人群,二者方法学有显著性差异。结论:酶联免疫分析法检测24h尿去甲基肾上腺素/甲氧基肾上腺素具有灵敏度高、特异性好的特点,为临床从肾上腺占位性病变并伴有阵发性高血压患者中筛查嗜铬细胞瘤提供了一种有价值的参考方法。     

能谱CT优化胃肿瘤扫描辐射剂量对肾上腺嗜铬细胞瘤的诊断价值

目的:探讨能谱CT优化胃肿瘤扫描辐射剂量对肾上腺嗜铬细胞瘤的诊断价值。方法:采用回顾性、抽样、随机研究方法选择2012年9月到2017年2月在我院诊治的肾上腺嗜铬细胞瘤患者59例作为研究对象,所有患者都给予常规CT扫描与能谱CT优化胃肿瘤扫描,记录和比较辐射剂量与图像质量。结果:所有病例包膜均完整,边缘清楚,肿瘤内见单发或多发低密度区,肿瘤实质区呈不均匀显著强化。常规CT与能谱CT的图像质量主观评分分别为3.89±0.45分和4.54±0.34分;常规CT与能谱CT图像的胃肿瘤CT值分别为31.94±6.39HU和35.29±5.19HU,对比都有显著差异(P0.05)。能谱CT图像的膀胱和皮下脂肪图像噪声值都显著低于常规CT图像,对比差异都有统计学意义(P0.05);能谱CT扫描的CTDIvol和DLP分别为12.39±3.48mGy和624.10±39.19mGy.cm,都显著低于常规CT扫描的14.09±4.13mGy和653.92±56.29mGy.cm(P0.05)。结论:能谱CT优化胃肿瘤扫描在肾上腺嗜铬细胞瘤诊断中的应用能有效减少辐射剂量与图像噪声,提高图像CT值与主观质量,临床应用价值更高。     

Distinguishing cortical adrenal gland adenomas from carcinomas by their quantitative nuclear features

OBJECTIVE: To explore data from a set of cases of adrenal cortical adenomas with different endocrine syndromes and carcinomas to determine whether quantitative image analysis of nuclear features might be used to separate the groups. STUDY DESIGN: Fifteen adrenal cortical tumors in which clinical information and optimally preserved, paraffin-embedded tissue were available were used. There were 10 adenomas and 5 carcinomas. Among the adenomas, five were associated with primary hyperaldosteronism (Conn's syndrome) and five with Cushing's syndrome. Five-micrometer-thick sections were stained with hematoxylin and eosin. In each case 50 nuclei were measured, and a number of morphometric and densitometric features were extracted. The data were subjected to multivariate analysis. RESULTS: Quantitative analysis showed that nuclei from adrenal carcinomas are larger than those from adenomas. Total optical density (OD) had a near-diploid distribution in the adenomas, while it was clearly aneuploid in the carcinomas. The pixel OD histograms were almost identical for all groups. Differences in nuclear chromatin texture were found between adenomas and carcinomas and also between the two adenoma categories. Multivariate analysis showed good discrimination between carcinomas and adenomas (Wilks lambda = .628, P < .0001) and between adenomas. However, based on Bayesian decision boundaries, 20-25% of carcinoma nuclei could be expected to be in the range of adenoma, and about 12% of Cushing's adenoma nuclei and 15% of Conn's adenoma nuclei would be classified as carcinoma. CONCLUSION: Computer-assisted analysis of nuclear characteristics proved useful in identifying and describing differences between groups of tumors arising in the adrenal cortex.     

THE RELATIONSHIP OF THE REFERRING PHYSICIAN TO THE PSYCHIATRIST

Tumors of the adrenal glands produce hormones which cause a variety of symptoms and signs including high blood pressure, excessive growth of hair on the body and precocious sexual development. By recently developed tests, it has been possible to differentiate high blood pressure due to these tumors from hypertension due to other causes. Removal of these tumors will often alleviate changes caused by them. Localization of the tumor and appraisal of the condition of the contralateral gland should be carried out preoperatively if possible. In this, several kinds of roentgen studies are helpful. Infusions of drugs during operation can be used to control the blood pressure which otherwise would vary widely. During a ten-year period (1942 to 1951) there were observed at the Los Angeles County General Hospital 100 proved cases of non-secreting and secreting primary neoplasms of the adrenal glands. In addition, there were three cases of Cushing's syndrome due to bilateral adrenal cortical hyperplasia, and ten probable cases (four, pheochromocytomas; five, Cushing's syndrome; one, adrenogenital syndrome) in which operation was not done.     

Immunolocalization of urotensin II and its receptor in human adrenal tumors and attached non-neoplastic adrenal tissues

Urotensin II (UII), first identified from goby urophysis, is a potent vasoactive peptide hormone and an endogenous ligand for an orphan G protein-coupled receptor GPR14, now named urotensin II receptor (UT-R). In addition to its vascular actions, UII has been shown to have mitogenic effects on tumor growth and some regulatory effects on adrenal steroidogenesis. In the present study, we examined expression of UII and UT-R in human adrenal tumors and attached non-neoplastic adrenal tissues by immunohistochemistry. Both UII and UT-R were immunolocalized in tumor cells of all adrenal tumors examined: 8 cases of cortisol-producing adenomas, 8 cases of aldosterone-producing adenomas, 2 cases of non-functioning adenomas, 17 cases of adrenocortical carcinomas, and 8 cases of pheochromocytomas. In attached adrenals, immunoreactivity for UII was detected in medulla, but much weaker in the cortex than in cortical tumors, suggesting that expression of UII was up-regulated in neoplastic adrenocortical tissues. No significant differences were found in the degree of immunoreactivity for UT-R between the tumors and the attached adrenal tissues. The present study showed that both UII and UT-R were expressed in the adrenal tumors and attached non-neoplastic adrenal tissues, and suggests possible roles of UII and UT-R in tumor growth and/or secretory activities of these tumors.     

Asymptomatic adrenal tumor; 386 cases in Japan including our 7 cases

To clarify the indication of surgery in incidentally discovered asymptomatic adrenal masses, we analyzed 386 Japanese cases, 379 cases reported in Japan during the past 25 years (from 1964 to 1988) and 7 cases from our own experience. From a total of 460 patients, we carefully selected 379 patients satisfying our criterion of the absence of symptoms and signs suggestive of active hormone over-secretion as described in each case report. From the Japanese series, there was a high incidence of pheochromocytoma patients (20 of 37 patients) who had no symptoms and signs but had high plasma or urine catecholamines. Scintigraphy with 131I-meta-iodo-benzyl-guanidine was useful in the diagnosis of pheochromocytoma. For the other asymptomatic adrenal tumors, except for myelolipoma and adrenal cyst, differential diagnosis between malignant and benign adrenal lesions by imaging procedures such as whole body computed tomography (CT), ultrasonography (US), adrenocortical scintigraphy, and angiography was not always possible. In addition, among the 109 patients with cortical tumors whose hormonal data were reported, no clear-cut differentiation of malignant tumor from benign by means of these data could be obtained. Since 1980 whole body CT scanner and high resolution US scanner have become widely available, and there have been 283 cases of asymptomatic adrenal tumors who satisfied our criterion. Cortical carcinomas smaller than 3 cm and 6 cm in diameter account for 3.8% and 6.6%, respectively, of the total of 101 cases of cortical carcinoma, cortical adenoma, ganglioneuroma, and hemangioma during this period. The size of the smallest cortical carcinoma with metastasis was 2 cm in diameter in this series. Pre-operatively, an adrenocortical carcinoma 2.8 cm in diameter in our patient could not be diagnosed as such by imaging techniques and measurement of plasma hormones. These findings suggest that an adrenal mass larger than 3 cm should be removed and a patient with a smaller cortical tumor should be carefully followed up.     

Operations on the adrenal glands

Various conditions of the adrenal gland are amenable to surgical treatment. Removal of a pheochromocytoma is almost always indicated when the tumor is diagnosed. The results of extirpation have been excellent in cases in which patients were operated upon before the onset of chronic hypertension. Removal of the "nerve cell" tumors of the adrenal is indicated if metastasis cannot be demonstrated. Hypofunction of the adrenal cortex may be partially alleviated by the repeated implantation of pellets of desoxycorticosterone acetate. Hyperfunction of the adrenal cortex causes a variety of clinical manifestations depending upon which of the numerous hormones are affected. Removal of a cortical tumor alleviates these symptoms. These tumors are malignant in more than 50 per cent of cases, and recurrence is frequent. Bilateral hyperplasia of the glands rather than a tumor may be present. In such circumstances, resection of 95 per cent of the adrenal tissue is effective in controlling the symptoms of the disease. Total bilateral excision of the adrenals is, at present, under investigation as a means of treatment for a variety of conditions.     

TREATMENT OF ASTHMA: Somatic and Psychiatric

Various conditions of the adrenal gland are amenable to surgical treatment. Removal of a pheochromocytoma is almost always indicated when the tumor is diagnosed. The results of extirpation have been excellent in cases in which patients were operated upon before the onset of chronic hypertension. Removal of the “nerve cell” tumors of the adrenal is indicated if metastasis cannot be demonstrated.Hypofunction of the adrenal cortex may be partially alleviated by the repeated implantation of pellets of desoxycorticosterone acetate. Hyperfunction of the adrenal cortex causes a variety of clinical manifestations depending upon which of the numerous hormones are affected. Removal of a cortical tumor alleviates these symptoms. These tumors are malignant in more than 50 per cent of cases, and recurrence is frequent. Bilateral hyperplasia of the glands rather than a tumor may be present. In such circumstances, resection of 95 per cent of the adrenal tissue is effective in controlling the symptoms of the disease.Total bilateral excision of the adrenals is, at present, under investigation as a means of treatment for a variety of conditions.     

Hyperparathyroidism associated with Cushing's syndrome due to an adrenal cortical adenoma

Two patients with the rare association of Cushing's syndrome and primary hyperparathyroidism are reported. Initially, both patients suffered from Cushing's syndrome due to adrenal cortical adenomas with typical features and laboratory findings. Five years after treatment of the Cushing's syndrome by removal of the tumor, asymptomatic mild hypercalcemia was incidentally noticed in both patients, which suggested the occurrence of primary hyperparathyroidism. An enlarged parathyroid gland was removed surgically in both cases and was histologically shown to be a parathyroid adenoma. The levels of serum calcium returned to normal after parathyroidectomy. Papillary adenocarcinoma of the thyroid in one patient and adenomatous goiter in the other were also incidentally detected at operation. These findings suggest that Cushing's syndrome resulting from an adrenal cortical adenoma may be another presentation of multiple endocrine neoplasia type I.     

Nestin expression in normal adrenal gland and adrenocortical tumors

Human adrenocortical cells have been shown to express cytokeratins and vimentin. Nestin is an intermediate filament protein that is mainly expressed in the developing nervous system and that has been recently reported in rat adrenal gland as well. Using immunohistochemical and biochemical approaches, the present study demonstrates that nestin is constantly expressed in situ in the cortex of normal human adrenal glands. Nestin expressing cells were prevalently located in the zona reticularis but some positive cells could be spotted in the zona fasciculata as well. Moreover, patches of nestin-positive cells have been constantly detected on sections of cortical adenomas. In contrast, adrenal carcinomas displayed a variable number of nestin-immunoreactive cells that in some cases were virtually absent. Samples of renal clear cell carcinoma metastasis in the adrenals were also examined which did not show nestin-immunoreactivity. We propose that a positive nestin-immunoreaction could be useful in differential diagnosis of clear cell tumors in adrenal glands.     

Adrenocortical tumors

Hormonally active tumors of the adrenal cortex are either benign adenomas or adenocarcinomas. They may be located within the adrenal gland or as adrenal rests along the Wolffian tract. Hyperplastic cortical tissue without actual neoplastic formation is also capable of elaborating excessive cortical secretions.AT THE PRESENT STATE OF KNOWLEDGE, ANY ONE OR A COMBINATION OF THE FOLLOWING COMPOUNDS MAY BE ELABORATED IN A GIVEN CASE: the electrolytic, glucogenic, androgenic, or estrogenic corticosteroids. Whether or not Cushing's syndrome is primarily pituitary or adrenal in origin is still a matter of conjecture.