Invasive Breast Carcinoma with Neuroendocrine Differentiation: A Single-Center Analysis of Clinical Features and Prognosis

Introduction Invasive breast cancer with neuroendocrine differentiation is a rare subtype of breast malignancy. Due to frequent changes in the definition of these lesions, the correct diagnosis, estimation of exact prevalence, and clinical behaviour of this entity may be challenging. The aim of this study was to evaluate the prevalence, clinical features, and outcomes in a large cohort of patients with breast cancer with neuroendocrine differentiation. Patients Twenty-seven cases of breast cancer with neuroendocrine differentiation have been included in this analysis. Twenty-one cases were identified by systematic immunohistochemical re-evaluation of 465 breast cancer specimens using the neuroendocrine markers chromogranin A and synaptophysin, resulting in a prevalence of 4.5%. A further six cases were identified by a review of clinical records. Results Median age at the time of diagnosis was 61 years. 70% of patients had T2 – 4 tumors and 37% were node-positive. The most common immunohistochemical subtype was HR-positive/HER2-negative (85%). 93% were positive for synaptophysin and 48% for chromogranin A. Somatostatin receptor type 2A status was positive in 12 of 24 analyzed tumors (50%). Neuroendocrine-specific treatment with somatostatin analogues was administered in two patients. The 5-year survival rate was 70%. Conclusions Breast cancer with neuroendocrine differentiation is mostly HR-positive/HER2-negative and the diagnosis is made at a higher TNM stage than in patients with conventional invasive breast carcinoma. Moreover, breast cancer with neuroendocrine differentiation was found to be associated with impaired prognosis in several retrospective trials. Due to somatostatin receptor 2A expression, somatostatin receptor-based imaging can be used and somatostatin receptor-targeted therapy can be offered in selected cases. Key words: neuroendocrine neoplasia of the breast, invasive breast cancer with neuroendocrine differentiation, neuroendocrine breast cancer, neuroendocrine markers, somatostatin receptor 2A     

基于反向滤波器的倒谱法估计平均骨小梁间距

目的 探讨用改进的倒谱方法估计平均骨小梁间距(mean trabecular bone spacing,MTBS)的可行性.方法 提出了一种基于反向滤波器的改进的倒谱分析方法用于估计MTBS,并将该方法应用于仿真及离体牛胫骨松质骨中的实验信号.结果 改进的倒谱方法能有效减少超声换能器脉冲响应和组织散射特性对倒谱的干扰,而且实现简单,计算量小.结论 相比于传统的倒谱方法,改进的倒谱方法在估计MTBS时, 对弥散散射和噪声有更强的鲁棒性,因此估计MTBS的精度更高.     

肝脏可溶性复合物不同剂量、不同途径移植对肿瘤细胞增殖抑制的体内外实验

目的:肝脏可溶性复合物具有保护肝脏、刺激肝组织再生等生物学活性,观察天然物质肝脏可溶性复合物对肿瘤细胞生长增殖的抑制作用.方法:实验于2006-05/2007-02在四川大学华西医院生物治疗国家重点实验室实验肿瘤研究室完成.①分离人胚胎、成年及新生小鼠肝脏组织,生理盐水清洗、剪碎、筛网过滤,用生理盐水制备混悬液,3 000 r/min离心,收集上清,制备肝脏可溶性复合物.②体外实验:用上述不同来源的肝脏可溶性复合物体外处理肿瘤细胞,四甲基偶氮唑盐比色法测定其对乳腺癌细胞EMT6增殖的影响.③体内实验:观察成年鼠肝脏可溶物质对乳腺癌细胞EMT6体内生长的抑制作用及其对荷瘤鼠生存状况的影响,包括不同给药剂量及不同给药途径两个实验,给药途径包括在接种肿瘤细胞部位的对侧腋下、同侧腋下、腹腔注射及灌胃等.结果:①体外实验显示不同来源的肝脏可溶性复合物能明显抑制肿瘤细胞EMT6增殖率,肿瘤增殖抑制率均显著高于血清白蛋白处理组(P＜0.05),并呈剂量依赖性.②成年鼠肝脏可溶物质8mg/L组抑瘤率高于2,4 mg/L组(P＜0.05),未观察到明显毒副效应.③比较不同给药途径,成年鼠肝脏可溶物质同侧注射组的抑瘤率较其他3组的抑瘤率高(P＜0.05),各成年鼠肝脏可溶物质给予组的体质量增长率比相应生理盐水对照组高(P＜0.05).④与相应生理盐水对照组比较,在同侧腋下注射成年鼠肝脏可溶物质的小鼠生存期明显延长(P＜0.05).结论:肝脏可溶性复合物具有抑制肿瘤细胞生长的作用,并且呈一定的剂量依赖性.不同的给药途径中,在接种肿瘤细胞部位的同侧腋下给药抑瘤效果最好.     

三维重建射频损伤区域观察猪舌根射频损伤体积与射频能量及时间的关系

目的：目前临床进行隧道法舌根射频治疗时,其作用参数的设置仍缺乏统一的标准,故通过计算机三维重建射频损伤区域,分析猪舌根射频损伤体积与射频能量、时间的关系,从中得出应用舌根隧道法射频治疗的最佳作用能级和作用时间。 方法：实验于2006-06/2007-05在上海交通大学耳鼻喉科研究所完成。将36只实验用猪以射频作用能级1,2,3,4,5,6随机分成6组,每组6头猪,各个猪舌的作用时间分别设置为2,5,10,15,20,25s。用Coblation射频发生仪及Reflex55刀头进行猪舌根射频操作。射频作用后的舌根组织行连续冰冻切片,苏木精-伊红染色后,进行序列组织切片的全貌二维图像采集,对拟重建的结构进行边界提取和图像分割。将提取分割图像导入Image-Pro Solution图像处理软件,利用3D Constructor插件进行三维重建,并根据设定参数进行体积计算。用SPSS10.0统计学软件对所测数据进行统计学分析。 结果：①作用能级固定时,舌根组织射频损伤体积随时间延长而增大,符合Logarithmic回归曲线。②作用时间固定时,舌根组织射频损伤体积随能级增大而增大,符合直线回归。③射频损伤体积随能量增大而增加亦符合Logarithmic回归曲线。④Coblation射频治疗系统在能级6时,在作用10s之前,损伤体积随作用时间增加而迅速增加,其后变化趋势平缓,超过20s后损伤体积无显著增加。 结论：①舌根区域射频治疗时,舌根组织射频损伤体积与时间或能量呈Logarithmic曲线相关,与能级呈直线相关。②Coblation射频治疗系统在能级6时,最佳作用时间范围为10-20s。     

构建Loa22基因去信号肽片段原核重组表达载体

目的：构建赖型钩端螺旋体OmpA膜蛋白Loa22基因去信号肽片段的原核表达载体，并对其进行克隆表达。方法：实验于2004—12／2005—12在四川大学华西医学中心感染免疫研究室完成。以赖型钩端螺旋体017株基因组DNA为模板，PCR扩增Loa22基因去信号肽片段，亚克隆至原核表达载体pGEX-4T-1，经双酶切、PCR鉴定，筛选出阳性重组质粒克隆。经DNA测序正确后，转化大肠杆菌，利用IPTG进行诱导表达，通过SDS—PAGE鉴定表达产物。结果：PCR获得长516bp的片段。Loa22基因去信号肽片段与pGEX-4T-1的重组质粒构建成功。重组质粒经IPTG诱导后能在大肠杆菌中表达Mr45000的融合蛋白。结论：制备了Loa22基因去信号肽片段原核重组表达载体，为钩体新型疫苗的研究奠定基础。     

Contrasting effects of recombinant human granulocyte-macrophage colony- stimulating factor (CSF) and granulocyte CSF treatment on the cycling of blood elements in childhood-onset cyclic neutropenia

Recombinant human granulocyte colony-stimulating factor (G-CSF) treatment has been shown to increase average neutrophil counts substantially in patients with childhood-onset cyclic neutropenia (or "cyclic hematopoiesis"), but not to eliminate the cyclic oscillations of neutrophil counts or those of other blood elements (monocytes, platelets, eosinophils, and reticulocytes) that are characteristic of this hematopoietic disorder. Indeed, oscillations of neutrophil counts are amplified during G-CSF treatment. We have compared the effects of recombinant granulocyte-macrophage-CSF (GM-CSF) with those of G-CSF in three patients with this disease (2 men and 1 woman, 17, 30, and 32 years of age). These patients were treated with GM-CSF (2.1 micrograms/kg/day, subcutaneously) for 6 weeks, preceded and followed by 6 to 13 weeks of detailed observation to document changes in the cyclic oscillations of blood neutrophils and other blood elements; two of the patients were subsequently treated with G-CSF (5.0 micrograms/kg/d, subcutaneously) and observed for comparable periods of time. Unlike G-CSF treatment, which increased average neutrophil counts more than 20-fold, GM-CSF increased neutrophil counts only modestly, from 1.6- to 3.9-fold, although eosinophilia of varying prominence was induced in each patient. However, at the same time, GM-CSF treatment dampened or eliminated the multilineage oscillations of circulating blood elements (neutrophils, monocytes, platelets, and/or reticulocytes) in each of the patients. In contrast, G-CSF treatment of the same patients markedly amplified the oscillations of neutrophil counts and caused the cycling of other blood elements (monocytes in particular) to become more distinct. These findings support the conclusion that the distinctive cycling of blood cell production in childhood-onset cyclic neutropenia results from abnormalities in the coordinate regulation of both GM-CSF-responsive, multipotential progenitor cells and G-CSF-responsive, lineage-restricted, neutrophil progenitors.     

How often does office hysteroscopy reveal pathology not previously noted on transvaginal ultrasound—a look at two typical reproductive endocrinology patient groups,including failed IVF–ET patients

Transvaginal ultrasound and office hysteroscopy are established diagnostic tools for the evaluation of infertility patients, with hysteroscopy often considered as the more precise method to evaluate the uterine cavity and ultrasound as the more readily available and less invasive method. We look at both methods in two typical infertility patient groups, including one group with a history of failed in vitro fertilization–embryo transfer (IVF–ET) cycles. Eighty patients were prospectively evaluated. Forty patients presented with a history of failed embryo transfer despite repeat normal transvaginal ultrasound examinations. Forty infertility patients with abnormal ultrasound testing served as a group for comparison. All patients underwent office hysteroscopy. In the subgroup with abnormal ultrasound findings, office hysteroscopy confirmed the diagnosis in 75% of cases but did not add new information. In patients with a history of failed embryo transfer and at least twice normal ultrasound examinations, only 1/40 patients (2.5%) was noted to have a minor abnormality on office hysteroscopy not previously diagnosed on ultrasound. In infertility patients, including those with a history of failed IVF–ET cycles, repeat normal transvaginal ultrasound appears to be an efficient method for the determination of significant intrauterine abnormalities.     

Pharmacologically Active Levels of PGE-, in Neonates with Congenital Heart Disease

ABSTRACT. In general, prostanoids act as local mediators, not as circulating hormones. A specific exception to this rule is the infusion of prostaglandin E₁ in patients with ductus arteriosus-depend-ent pulmonary or systemic blood flow associated with congenital heart disease. We therefore measured prostaglandin E, plasma levels by gas chromatography-mass spectrometry during effective infusion of prostaglandin E₁ in 10 neonates. Prostaglandin E₁ plasma levels ranged from 22 to 530 (median 56) pg/ml in these patients. Since prostaglandin E₁ is not synthesized endogenously to any significant extent, these plasma concentrations constitute genuine circulating levels not confounded by the common problem of e vivo artifacts. If endogenous prostanoids (e.g. prostaglandin E₂) are suspected as circulating mediators, plasma levels detected by reliable methods ought to be in the same range as prostaglandin E₁ plasma levels in the present investigation.     

Influence of the Maternal Plasma Glucose Concentration at Delivery on the Risk of Hypoglycaemia in Infants of Insulin-Dependent Diabetic Mothers

Plasma glucose concentrations at birth and at two hours of age were measured in 53 infants of insulin-dependent mothers (IDMs). The plasma glucose concentrations at delivery were measured in the mothers of 17 IDMs and in the remaining 36 mothers, glucose was estimated by interpolation from concentrations achieved just before and after delivery. Clinical and laboratory data from the two groups were otherwise similar, so the groups were combined for further analyses. The maternal plasma glucose at delivery correlated positively with the glucose concentration of the IDMs at birth (Q=0.82, p <0.001) and negatively with the glucose concentration at two hours of age (Q= -0.46, p <0.001). Maternal plasma glucose concentration was higher in mothers delivered by caesarean section than in vaginally delivered mothers ( p <0.05). Eleven IDMs became hypoglycaemic at two hours of life (plasma glucose ≥1.7 mmol/1). These infants had higher cord plasma glucose concentrations at birth than those who remained normoglycaemic; the maternal glucose concentration was also higher. None of the IDMs became hypoglycaemic if the maternal glucose concentration at delivery was less than 7.1 mmol/l. In 28 IDMs the simultaneous plasma concentrations of non-antibodybound immunoreactive insulin (IRI) were recorded. Cord plasma IRI correlated with glucose and IRI at two hours of age (Q=-0.73, p <0.001 and Q=0.77, p <0.001, respectively). Cord plasma IRI was higher in IDMs who became hypoglycaemic than in the remaining infants. The results suggest that among the factors which may be responsible for neonatal hypoglycaemia in IDMs a major factor may be the maternal plasma glucose concentration at the time of delivery.     

The neuroendocrine recovery function of sleep

The hypothalamo-pituitary-adrenal (HPA) system is a most important mediator of the organism's response to stress. Secretory activity of this endocrine system displays a specific regulation during normal nocturnal sleep in humans. Pituitary release of adrenocorticotropin (ACTH) as well as adrenocortical release of cortisol decreases to a minimum during early sleep which is simultaneously characterized by maximum release of growth hormone (GH) and a predominance of slow wave sleep (SWS). In contrast, release of ACTH and cortisol reaches a maximum during late sleep which is simultaneously characterized by minimum plasma concentrations of GH and a predominance of rapid eye movement (REM) sleep. The nadir activity of the pituitary-adrenal system during early sleep reflects an active inhibition of this 'stress' system. One of the factors mediating this inhibition presumably is the sleep associated hypothalamic secretion of a release inhibiting factor of ACTH. In addition, limbic-hippocampal neuronal networks contribute to the inhibitory control over HPA activity during early sleep. Those structures appear to coordinate HPA inhibition and cortical activity (with prevalent SWS) during early sleep, thereby facilitating the formation of memories in sleep. As indicated by studies testing the effects of elevated plasma glucocorticoid levels, the inhibition of HPA activity during early sleep is an essential prerequisite for the memory function of sleep. Possibly, immunological memory formation likewise benefits from this inhibition. The suppression of pituitary-adrenal secretory activity during early sleep can be significantly weakened after profound acute stress as well as in states of chronic stress (including normal aging) which thereby disturb regular memory formation in sleep.