The neural regulation of the mammalian esophageal motility and its implication for esophageal diseases

In contrast to the tunica muscularis of the stomach, small intestine and large intestine, the external muscle layer of the mammalian esophagus contains not only smooth muscle but also striated muscle fibers. Although the swallowing pattern generator initiates the peristaltic movement via vagal preganglionic neurons that project to the myenteric ganglia in the smooth muscle esophagus, the progressing front of contraction is organized by a local reflex circuit composed by intrinsic neurons similarly to other gastrointestinal tracts. On the other hand, the peristalsis of the striated muscle esophagus is both initiated and organized by the swallowing pattern generator via vagal motor neurons that directly innervate the muscle fibers. The presence of a distinct ganglionated myenteric plexus in the striated muscle portion of the esophagus had been enigmatic and neglected in terms of peristaltic control for a long time. Recently, the regulatory roles of intrinsic neurons in the esophageal striated muscle have been clarified. It was reported that esophageal striated muscle receives dual innervation from both vagal motor fibers originating in the brainstem and varicose intrinsic nerve fibers originating in the myenteric plexus, which is called ‘enteric co-innervation’ of esophageal motor endplates. Moreover, a putative local neural reflex pathway that can control the motility of the striated muscle was identified in the rodent esophagus. This reflex circuit consists of primary afferent neurons and myenteric neurons, which can modulate the release of neurotransmitters from vagal motor neurons in the striated muscle esophagus. The pathogenesis of some esophageal disorders such as achalasia and gastroesophageal reflux disease might be involved in dysfunction of the neural networks including alterations of the myenteric neurons. These evidences indicate the physiological and pathological significance of intrinsic nervous system in the regulation of the esophageal motility. In addition, it is assumed that the components of intrinsic neurons might be therapeutic targets for several esophageal diseases.     

WAVEs亚家族在卵巢癌中的表达及临床意义

目的 探讨WAVEs亚家族在卵巢癌(oc)中的表达及其与临床病理特征的关系.方法 用免疫组化法检测60例OC、25例卵巢交界性肿瘤、30例卵巢良性肿瘤和21例正常卵巢组织中WAVEs蛋白的表达,结合临床病理资料进行分析;反转录聚合酶链反应法(RT-PCR)和Western blot分别检测WAVEs mRNA和蛋白表达.结果 1)WAVE1在OC中的表达显著高于正常卵巢组织、卵巢良性组织和卵巢交界性组织(P＜0.01).2)WAVE1在OC中的表达与临床分期、病理分化程度及Ca-125水平密切相关(.P＜0.05),而与年龄、肿瘤大小及腹水量无关.3)WAVE1在OC中mRNA、蛋白水平显著高于正常卵巢组织、卵巢良性肿瘤和交界性肿瘤(P＜0.01).而WAVE2、WAVE3在各组表达均低.结论 WAVE1在OC中高表达,可能与其发生发展及侵袭转移有关,可望成为卵巢癌治疗的靶标.     

The assessment of HER2 status and its clinical implication in breast cancer

Amplification and overexpression of human epidermal growth factor receptor 2 (HER2) in breast cancer is associated with an adverse prognosis. The introduction of trastuzumab and lapatinib has substantially improved the clinical outcomes of patients with HER2-positive breast cancer. The key element of the successful application of anti-HER2 therapies in real-world has been the selection of candidates for treatment based on the level of HER2 positivity of the tumor. HER2 status of breast cancer is clinically assessed by HER2 protein expression with immunohistochemistry (IHC) or HER2 gene amplification with in situ hybridization (ISH). The 2018 American Society of Clinical Oncology and the College of American Pathologists (ASCO/CAP) HER2 guideline focused update revised the HER2 scoring criteria. Digital image analysis (DIA) has emerged as an objective and reproducible IHC scoring method and the ASCO/CAP HER2 guideline has acknowledged DIA as a diagnostic modality. In this article, we aim to review the assessment of HER2 status and its clinical application in breast cancer.     

The diagnosis and management of esophageal perforations

Despite the widespread availability of flexible fiberoptic upper gastrointestinal endoscopes, perforation of the esophagus continues to pose a formidable diagnostic and therapeutic problem for the clinician. Failure to recognize and treat a contained mediastinal perforation can result in death in a matter of hours. The most common etiology is still iatrogenic; therefore, attention to detail and proper training for endoscopists is paramount in reducing the morbidity and mortality associated with this disorder. This article reviews the diagnosis and treatment of esophageal perforation and discusses measures to avoid this potentially lethal complication.     

The changing landscape of gynaecological cancer diagnosis: implications for histopathological practice in the 21st century

The era of molecular medicine has led to dramatically improved understanding of the genetic events that give rise to different types of cancers. In the case of gynaecological malignancies, this has resulted in distinct shifts in how these tumours are diagnosed in routine surgical pathology practice, with an increased emphasis on accurate subtype diagnosis. This has happened across all sites in the gynaecological tract and for most cell types, but in ways that are site‐specific and may appear to be subtle, as in most instances the diagnostic terminology has not changed. For example, the diagnosis of clear cell carcinoma of the ovary is still in use, but the diagnostic criteria and clinical implications are different in 2017 from what they were in 2000. As a result, there can be a failure to appreciate how important these changes are and the resulting necessity of incorporating them into our daily practice. In this review we will describe changes in diagnostic surgical pathology occasioned by improved understanding of molecular events during pathogenesis, for cancers of ovary/tube, endometrium, cervix and vulva, and highlight how current practice differs from that of only a few years ago.     

The changing survival profile of people with Down's syndrome: implications for genetic counselling

Cohort studies have indicated that the survival of individuals with Down's syndrome has dramatically increased over the past 50 years. Early childhood survival in particular has shown major improvement, due largely to advances in cardiac surgery and in general health management. The present study was based on a continuous cohort of 1332 people with Down's syndrome in Western Australia, registered for intellectual disability services between 1953 and 2000. Their life expectancy was 58.6 years, 25% lived to 62.9 years, and the oldest living person is 73 years of age. Life expectancy for males was greater than females by 3.3 years. The substantial increase in survival across the study period means that the life expectancy of people with Down's syndrome is approaching that of the general population, but accompanied by a range of significant mid-life health problems. The findings are of relevance to all developed countries and have considerable implications in terms of the counselling information provided to families at risk of having a child with Down's syndrome.     

The changing profile of a nineteenth-century asylum: the York Retreat

This paper focuses on the later history of the York Retreat after the initial period for which it is best known. It discusses the marked changes which occurred in the social composition of its patients and the way in which these changes modified the asylum's management and therapy. It argues that the conventional image of the Retreat, based as it is on the institution's earliest years, needs considerable revision.     

Extensive pigmented villonodular synovitis with markedly pigmented lymphadenopathy and its implication for differential diagnosis with malignant melanoma

A 51-year-old male presented with a 5 cm left knee mass. Fine needle aspiration revealed large epithelioid cells with prominent nucleoli and abundant cytoplasmic pigment, consistent with malignant melanoma. Left inguinal lymphadenopathy was present, which was suspicious for metastatic disease by ultrasound examination. A dark perianal skin lesion was also identified, therefore raising the possibility of a primary melanoma. The knee and perianal lesions were resected and inguinal sentinel node biopsy was performed. In the specimen from the knee, there were clusters and fascicles of spindle and epithelioid cells with prominent nucleoli. Many of the cells displayed abundant, granular, brown, cytoplasmic pigment. The lymph node showed clusters of similar cells located in the subcapsular sinus. Immunohistochemical study showed that the cells expressed CD68, but failed to express S-100, MART-1, and gp100. The cytoplasmic pigment was positive for iron staining. The final diagnosis was pigmented villonodular synovitis. This case illustrates that pigmented villonodular synovitis may present with lymphadenopathy, mimicking a malignant process, including melanoma. Immunohistochemical studies may be essential for establishing the correct diagnosis.     

Expression of protein tyrosine phosphatases and its significance in esophageal cancer

Expression of mRNA protein tyrosine phosphatases (PTPs) was surveyed in an esophageal cancer cell line by RT-PCR using degenerate primers. The mRNAs for eight kinds of PTPs were expressed in the cell line. We examined mRNA expression of these PTPs in 12 cases of esophageal cancer by Northern analysis. Significant signals were obtained for three kinds of PTPs, PTP1B, PTPH1, and PTPD1. The magnitude of expression of each PTP was measured as the ratio of the signal intensity of each PTP to that of a control gene (NADPH), and the ratio was then compared to normal mucosa around the cancer lesion. Among the three kinds of PTPs, the expression of PTP1B mRNA was significantly depressed in cancer lesions compared with that in the surrounding normal mucosa. In contrast, the expression of PTPH1 mRNA was significantly increased in cancer lesions compared with that in normal mucosa. PTPD1 did not show any significant trend in comparisons of cancer and surrounding normal mucosa. The results suggest that PTP1B and PTPH1 are engaged in opposing signaling pathways, the tumor-suppressive and tumor-promoting pathways, respectively, in esophageal carcinogenesis.     

食管的迷走神经分布特征及其在食管癌外科治疗中的意义

目的:观测全程食管的神经来源与分布特点,为临床行迷走神经保留式食管切除微创术提供解剖学基础。方法:50例防腐固定的成人尸体标本,解剖观测食管各部的神经来源、分支分布特点及其主要分支的横径,并对结果进行统计学处理。结果:①食管颈、胸、腹3部的神经分别来源于迷走神经和交感干的分支,各部分支形式和密度不同;②左、右迷走神经主干沿食管两侧缘下行,与食管壁外膜以疏松结缔组织相连;③迷走神经在胸部的主要食管支和交通支与支气管和膈肌食管裂孔之间具有一定距离;④在胸部,迷走神经分出集中分支前、后的横径,左侧分别为(3.01±0.14)mm和(1.80±0.23)mm;右侧分别为(3.04±0.16)mm和(1.52±0.21)mm。结论:①食管的迷走神经来源于喉返神经、迷走神经主干和颈、胸交感干的分支;②临床上在术中可切断迷走神经的前或后交通支,保留其完整的左、右主干,对改善食管癌切除和食管-胃吻合术后胃肠功能以及预防复发性食管癌可能具有重要的意义。     

精氨酸酶1在食管癌患者外周血的表达及其临床意义

目的检测精氨酸酶1(arginase1,Arg1)在食管癌中的表达,分析其与髓源性抑制细胞(myeloid-derived suppressorcells,MDSCs)消长的关系,探讨癌症患者机体免疫抑制状态的可能机制。方法应用流式细胞术检测30例食管癌患者PBMC中的MDSCs比例;实时荧光定量PCR检测PBMC中Arg1、IL-6和TNF-αmRNA的表达水平;酶联免疫吸附试验(ELISA)检测血浆Arg1,IL-6和TNF-α含量。结果食管癌患者外周血PBMC中MDSCs比例及Arg1的mRNA水平均明显高于健康对照组(P<0.05),而IL-6和TNF-α的mRNA水平均低于健康对照组(P<0.05)。食管癌患者血浆Arg1含量高于健康对照组(P<0.05),而IL-6和TNF-a含量与健康对照组相比无明显差异(P>0.05)。此外,食管癌患者Arg1 mRNA水平和蛋白水平均与MDSC含量呈正相关(P<0.01)。结论 Arg1在食管癌患者外周血中的高表达与MDSCs水平和食管癌的发生、发展有着密切的关系,其检测将有助于临床食管癌的辅助诊断和预后判断。     

Raf激酶抑制蛋白在宫颈癌中的表达及其临床意义

目的 探讨Raf激酶抑制蛋白(Raf kinase inhibitor protein,RKIP)在宫颈癌中的表达及其临床意义.方法 应用免疫组织化学方法检测RKIP在正常官颈组织、官颈上皮内瘤变组织、官颈癌及其转移淋巴结组织的表达,并在体外应用RT- PCR及Western印迹方法检测RKIP mRNA及蛋白在4种不同来源的宫颈癌细胞系中的表达情况,探讨其与官颈癌临床病理学特征的关系.结果 RKIP在宫颈癌转移淋巴结中的阳性表达率低于宫颈癌组织;RKIP在宫颈癌组织的表达低于正常宫颈组织及宫颈上皮内瘤变组织,差异有统计学意义(x2 =9.211,P＜0.05);而RKIP在正常官颈组织及官颈上皮内瘤变组织的表达差异无统计学意义(x2=0.805,P＞ 0.05);RKIP在宫颈癌组织中的表达与淋巴结转移有关(x2=10.341,P＜0.05),与肿瘤的病理类型、分化程度及临床分期无关(x2分别为0.190、4.101、1.402,P＞0.05).RT- PCR及Western印迹结果显示RKIP在高侵袭性宫颈癌细胞系Caski中的表达低于其他各组(x2=4.08,P＜0.05).结论 RKIP基因在宫颈上皮内瘤变向官颈癌转变中可能起重要作用,是官颈癌发生淋巴结转移的重要标记.