Carcinoid Tumor of the Middle Ear Containing Serotonin and Multiple Peptide Hormones A Case Report and Review of the Pathology Literature

A 69-year old man complaining of longstanding hearing loss and mild otorrhea was found to have a mass obliterating the external auditory canal and polypous tympanic mucosa with accompanying absence of the tympanic membrane and ossicular chain. Tumors excised from the external auditory canal and tympanum showed histologic features essentially characteristic of a carcinoid tumor: a ribbon or festoon arrangement of tumor cells, formation of anastomosing cords and glandular spaces, presence of numerous argyrophilic as well as argentaffin secretory granules within many of the tumor cells, and ultrastructur-al evidence of neurosecretory granules in the tumor cell cytoplasm. Immunohistochemically, the tumor was found to contain not only neuronal marker substances such as neuron-specific enolase, S 100 protein and chromogranin A, but also serotonin and multiple peptide hormones such as pancreatic polypeptide, glucagon, cholecystokinin and leucine-enkephalin. A review of the pathology of 17 previous cases of carcinoid of the middle ear suggested that this type of carcinoid may have a variegated hormone profile among carcinoids of foregut origin, and hormonally may resemble ileal carcinoid arising from the midgut, although their histogenetic origins may differ, because of frequent production of serotonin. Acta Pathol Jpn 42: 614–620, 1992.     

Nocturnal hormonal responses to resistance exercise

The effects of resistance exercise on the nocturnal responses of cortisol (CO), testosterone (TEST), human growth hormone (hGH), and thyroid hormones (T₃, T₄) were examined in eight trained weight lifters. Each subject completed two trials using a counterbalanced design: a control, no exercise trial (CON) and a heavy resistance exercise session of three sets of six exercises to exhaustion (RE). The exercise session took place between 1900 and 2000 hours. Blood was sampled prior to and at 20-min intervals after RE. For both trials blood was sampled at hourly intervals from 2100 hours until 0700 hours. The hGH and CO concentrations were increased up to 40-min post-exercise (P < 0.05), but returned to resting levels 1 h post-exercise. Nocturnal hGH concentration was not affected by RE (P > 0.26) and peaked at 0200 hours and declined until 0700 hours. Similarly, the CO responses were similar between the trails (P > 0.14). This CO concentrations declined from 2200 hours until 0100 hours, then increased steadily until 0700 hours. The TEST concentrations during both trials rose steadily from 2200 hours until 0700 hours; however, the rise in TEST from 0500–0700 hours during RE was greater than during the CON trails (P = 0.059). The T₃ concentrations were unchanged by exercise and were similar at all times between trails. The T₄ concentrations were elevated for 20 min after RE; however nocturnal T₄ concentrations were lower after RE than during CON. These results would suggest that bGH and CO may have limited nocturnal reactivity to resistance exercise. However, the nocturnal alterations of TEST and T4 after resistance exercise, although small, may have implications for muscle anabolism.     

The endocannabinoid system in the physiology and pathophysiology of the gastrointestinal tract

Numerous investigations have recently demonstrated the important roles of the endocannabinoid system in the gastrointestinal (GI) tract under physiological and pathophysiological conditions. In the GI tract, cannabinoid type 1 (CB1) receptors are present in neurons of the enteric nervous system and in sensory terminals of vagal and spinal neurons, while cannabinoid type 2 receptors are located in immune cells. Activation of CB1 receptors was shown to modulate several functions in the GI tract, including gastric secretion, gastric emptying and intestinal motility. Under pathophysiological conditions induced experimentally in rodents, the endocannabinoid system conveys protection to the GI tract (e.g. from inflammation and abnormally high gastric and enteric secretions). Such protective activities are largely in agreement with anecdotal reports from folk medicine on the use of Cannabis sativa extracts by subjects suffering from various GI disorders. Thus, the endocannabinoid system may serve as a potentially promising therapeutic target against different GI disorders, including frankly inflammatory bowel diseases (e.g. Crohns disease), functional bowel diseases (e.g. irritable bowel syndrome) and secretion- and motility-related disorders. As stimulation of this modulatory system by CB1 receptor agonists can lead to unwanted psychotropic side effects, an alternative and promising avenue for therapeutic applications resides in the treatment with CB1 receptor agonists that are unable to cross the blood–brain barrier, or with compounds that inhibit the degradation of endogenous ligands (endocannabinoids) of CB1 receptors, hence prolonging the activity of the endocannabinoid system.     

胃肠道癌患者血清中抗癌胚抗原(CEA)抗体的检测及意义

目的：探讨循环中抗癌胚抗原（ＣＥＡ）特异性抗体的情况，评价ＣＥＡ及抗体的联合检测在胃肠道癌诊断中的作用。方法：用放免法检测血清中 ＣＥＡ含量，用酶联免疫吸附法（ＥＬＩＳＡ）检测抗 ＣＥＡ ＩｇＧ抗体，用竞争抑制法检测抗体的特异性。结果：胃肠道癌患者血清 ＣＥＡ含量升高者（≥１５ ｎｇ／ｍｌ）为 ３０．９％（２１／６８），抗 ＣＥＡ ＩｇＧ抗体阳性者为３５．３％（２４／６８），ＣＦＡ及抗 ＣＥＡ抗体的联合检测可使阳性率提高到５４．３％（３７／６８）；胃肠道良性疾病患者（多发性息肉、溃疡、胰腺炎等）血清ＣＥＡ升高者为３．３％（１／３０），抗 ＣＥＡ　ＩｇＧ抗体阳性者为 ３．３％（１／３０）；健康对照组血清 ＣＥＡ升高者为 ０，抗 ＣＥＡ ＩｇＧ抗体阳性者为 ２．５％（１／４０）。结论：胃肠道癌患者血清中抗癌胚抗原（ＣＥＡ）抗体的检出率较高，这些抗体可作为胃肠道癌的一种肿瘤标志物。     

Generalized AA-amyloidosis in a 58-year-old Caucasian woman with an 18-month history of gastrointestinal tuberculosis

 We report on a 58-year-old Caucasian woman who went to a general practitioner about recurrent abdominal pain, night sweats and weight loss of a few weeks’ duration. Once gynaecological disease had been ruled out, the patient was admitted to hospital with severe abdominal pain and intestinal obstruction and a right-sided hemicolectomy was performed. Following the investigation of osteolytic lumbar vertebrae, 18 months after visiting the general practitioner the patient was finally found to be suffering from generalized AA-amyloidosis secondary to gastrointestinal tuberculosis. This had been misinterpreted as Crohn’s disease. Re-examination of the specimens from the right-sided hemicolectomy demonstrated that scanty deposits of AA-amyloid were present 9 months after the first presentation. AA-amyloid can thus be present in serious inflammatory disease even during the first 9 months after the initial clinical presentation. Received: 23 June 1998 / Accepted: 19 August 1998     

Immunohistochemical distribution of chromogranins A and B and secretogranin II in neuroendocrine tumours of the gastrointestinal tract

The aim of the present study was to investigate immunohistochemically the distribution of chromogranin A, chromogranin B, and secretogranin II in a series of 152 neuroendocrine tumours of the gastrointestinal tract. Tumour tissues from 25 argyrophil gastric carcinoids, 18 gastrin and 5 somatostatin-producing tumours, 4 gangliocytic paragangliomas, 49 classical argentaffin and 2 L cell appendiceal carcinoids, 27 classical ileal carcinoids, 17 rectal carcinoids, and 5 poorly differentiated neuroendocrine tumours of the stomach and rectum were immunostained with antibodies against chromogranin A, chromogranin B, and secretogranin II. Chromogranin A was the major granin expressed in gastric carcinoids and in serotonin-producing carcinoids of the appendix and the ileum. In contrast, strong chromogranin B and secretogranin II immunoreactivity was found in rectal carcinoids, in which chromogranin A was rarely expressed. Since chromogranin A is a widely used marker for neuroendocrine differentiation, it is of diagnostic importance that some gastrin-producing tumours, gangliocytic paragangliomas, poorly differentiated neuroendocrine carcinomas, and appendiceal L cell carcinoids completely lacked chromogranin A positivity. It is concluded that the various neuroendocrine tumours of the gastrointestinal tract show distinctly different patterns of granin expression, probably reflecting their histogenetical origin.     

Primary polypeptide hormones and mucin-producing malignant carcinoid of the larynx

A case of primary malignant laryngeal carcinoid with dual endocrine and mucous differentiation i s reported. Histologically the tumor showed a characteristic organoid pattern and exhibited Alcian-blue, periodic acidschiff, and Grimelius silver positivity. By the immunoperoxidase technique cal citoni n, ACTH, and or-hCG subunit were demonstrated in the tumor cells. ELectron microscopy revealed two different types of endocrinelike cells: mucous cells and occasional cells containing both endocrinelike granules and mucin droplets. Diagnostic morphologic criteria of this rare tumor entity are discussed and reference t o biologic behavior and possible h istogenesis is made.     

Pancreatic endocrine tumours associated with WDHA syndrome

Summary Nine pancreatic endocrine tumours of patients with watery diarrhoea hypokalaemia achlorhydria (WDHA) syndrome were examined by immunohistochemistry and electron microscopy. All cases revealed neoplastic proliferation of VIP (vasoactive intestinal peptide)-immunoreactive (IR) cells. Immunoreactivity to a novel peptide hormone PHM-27, which is processed from a common big precursor peptide of VIP (prepro VIP/PHM-27), was identified in VIP-IR cells of 8 tumours. VIP-PHM-IR cells had secretory granules measuring about 130 to 220 nm in diameter. Radioimmunoassay of tumour tissue extracts showed high VIP and PHM contents in proportional amounts in most cases. According to the results of immunostaining, the 8 tumours fell into two large groups; 5 with PP (pancreatic polypeptide)-IR cells and 3 with CT (calcitonin)-IR cells. The former group demonstrated VIP cells and PP cells intermingled in various proportions, including one tumour in which coexistence of PP-IR and VIP-IR in the same cells was demonstrated. Cell heterogeneity of the tumours and possible relationships of VIP, PP and CT cells were discussed.This work was supported in part by Grants-in-Aid for Cancer Research from the Ministry of Health and Welfare and from the Ministry of Education, Science and Culture, Japan     

MUC1/Y基因体外冲击树突状细胞诱导抗瘤免疫反应

目的制备含MUC1/Y cDNA质粒转染的树突状细胞(DC),体外诱导杀伤细胞,研究其治疗消化道肿瘤的效果.方法构建MUC1/Y cDNA真核表达载体pIRES2-EGFP-MUC1/Y、pcDNA3.1-MUC1/Y.以pcDNA3.1-MUC/Y电转染8例HLA-A2(+)消化道肿瘤患者单个核细胞衍生的DC后,与自体T细胞混合培养,诱导CTL(T-pcDAN3.1-MUC1/Y).以SW620细胞[HLA-A2(+)、MUC1/Y(+)]为特异性靶细胞,Raji细胞[HLA-A2(-)、MUC1/Y(-)]和Lovo细胞[HLA-A2(-)、MUC1/Y(+)]为非特异性靶细胞,通过乳酸脱氢酶(LDH)释放实验测定杀伤活性,ELISA法检测基因修饰后DC刺激自体T细胞产生IFN-γ的能力,并以ANNEXIN V-FITC试剂盒检测特异性CTL诱导靶细胞凋亡情况.结果pIRES2-EGFP-MUC1/Y转染效率为8%左右.T-pcDAN3.1-MUC1/Y诱导的杀伤作用显著高于T-pcDNA3.1[pcDNA3.1(+)修饰DC诱导的CTL]和T-IL-2(IL-2刺激外周血单个核细胞产生的CTL),P＜0.05.而且T-pcDNA3.1-MUC1/Y对靶细胞的杀伤和诱导凋亡的能力显著高于对照组.基因修饰后的DC能刺激自体T细胞分泌高水平IFN-γ,与未转染的DC相比具有显著差异(P＜0.05).结论成功构建MUC1/Y全长cDNA真核表达载体.pIRES2-EGFP-MUC1/Y可用于真核细胞转染,通过观察转染效率,易于筛选阳性克隆;经pcDNA3.1-MUC1/Y修饰的DC可有效诱导特异性抗肿瘤免疫应答.