穿山甲胃癌及其病因的研究

1981年,我们首次从穿山甲(Manis中pcntadactylus)发现了胃的良性肿瘤,1982年发现了恶性肿瘤。1953年,作者又对50只穿山甲的胃脏进行了研究。经病理诊断证实,总计在1981—1983年间,于72只穿山甲共检出胃鳞状细胞癌7例、胃乳头状瘤4例(其中一例已癌变)和胃腺瘤性息肉一例。此     

中国穿山甲消化道5-羟色胺免疫活性细胞的定位

目的研究中国穿山甲消化道5-羟色胺（5-HT）免疫活性细胞的分布和形态。方法应用链霉菌抗生物素蛋白一过氧化物酶免疫组织化学方法（S-P法）。结果中国穿山甲消化道5-HT细胞在胃幽门部密度最高,食道、胃贲门部和胃体中未见分布。肠道5-HT细胞密度从十二指肠、空肠到回肠依次减少,至大肠又显著升高（P〈0．01）。5-HT细胞形态多样,主要有圆形、椭圆形和锥形,肠上皮中锥形5-HT细胞通过顶部较长的胞突通向肠腔,基部较宽的胞体与固有层相接触。结论中国穿山甲消化道5-HT细胞的分布和形态同其它动物有相似之处,也有其自身特点。中国穿山甲消化道中5-HT细胞的分布与其食性是相适应的。     

SOX18在胃腺癌中的表达及临床意义

目的探讨SOX18在胃腺癌中的表达与临床病理特征的关系,分析其在胃腺癌中的作用。方法利用免疫组织化学SP法检测60例胃腺癌及其相应(15例)远端正常胃黏膜组织中SOX18的表达。结果胃腺癌中SOX18的阳性表达率为76.7%(46/60),显著高于正常粘膜组织中的30.0%,差异具有统计学意义(P0.05)。胃腺癌中SOX18蛋白的表达与肿瘤浸润深度、淋巴结转移及TNM分期有关(P0.05),与患者年龄、性别、Lauren组织学分型及肿瘤分化程度均无关(P0.05)。结论 SOX18在胃腺癌中的高表达可能与胃癌的发生、发展和淋巴结转移密切相关。     

Caspase-9在胃间质瘤中表达下调的临床病理学意义

目的了解caspase-9在胃间质瘤中的表达及其与临床病理特征的关系。方法采用实时荧光定量PCR技术检测108例胃间质瘤患者的肿瘤组织和胃壁正常组织中caspase-9 m RNA的表达;免疫组织化学染色检测其蛋白表达水平。通过卡方检验判断caspase-9表达变化与胃间质瘤的临床病理学特征的关系。结果 Caspase-9 m RNA在胃间质瘤组织的表达较正常胃壁组织低,且无论是m RNA还是蛋白水平,caspase-9表达变化与胃间质瘤的核分裂象均密切相关,caspase-9表达下调的患者核分裂象高的可能性更大。结论 Caspase-9在胃间质瘤中低表达,且表达下调的肿瘤的核分裂象更高,提示可能与胃间质瘤的发生发展及预后有关。     

胃癌患者发病部位、发病年龄以及临床病理特征之间的关系

目的:探讨胃癌患者发病部位、发病年龄年龄以及临床病理特征之间的关系。方法:选取2008年1月～2017年12月哈医大一院及哈医四院普外科经手术治疗的1200例胃癌患者,对其发病部位、发病年龄与性别、肿瘤大小、Borrmann分型、大体分型、病理分化类型等情况进行统计学分析。结果:在113例早期胃癌患者中,60例发病部位在胃窦小弯部,占53.1%;胃体小弯部29例,占25.7%;胃角部14例,12.4%;贲门部10例,占8.8%。不同发病部位患者性别构成比较差异存在明显的统计学意义(P0.05),但年龄、肿瘤大小、大体分型、病理分化类型比较差异无统计学意义(P0.05)。在1087例进展期胃癌患者中,好发部位以胃窦部最多,为608例(55.9%),其次是胃底贲门部249例(22.9%)和胃体部173(15.9%)。不同发病部位患者性别构成比较冲压存在明显的统计学意义(P0.05),而患者年龄、肿瘤大小、Borrmann分型、病理分化类型比较冲压无统计学意义(P0.05)。在不同年龄组别胃癌患者的统计中,全组男女总比为2.3:1,在≤40岁组中男女比例为1.1:1,40岁≤60岁组中男女比例为2.4:1,60岁组中男女比例为2.9:1,三组对比(x~2=8.39,P0.05)存在明显统计学意义;在病理学分化类型的三组对比中,以低分化腺癌为主占91.7%,但随着年龄的增长,高分化腺癌比例有所增加(x~2=16.74,P0.05)存在明显统计学意义;而发病部位以胃下部1/3最多649例,占54.1%,三组对比无明显统计学意义;肿瘤大小以2 cm≤5 cm最多567例,占47.3%,三组对比无明显统计学意义;Borrmann分型以BorrmannⅢ型最多594例,占49.5%,三组对比无明显统计学意义。结论:无论早期胃癌还是进展期胃癌,好发部位以胃窦小弯部最多;胃癌发病部位与性别存在一定关系,在早期胃癌中,发病部位越高,女性患者比例越大;在进展期胃癌中,胃癌发生的位置越高,男性比例越大;此外,胃癌患者年龄越小,女性比例越大;胃癌患者年龄越大,高、中分化腺癌的比例越大。胃癌患者的发病部位与临床病理特征无明显相关性。     

胃癌患者组织中DLC-1和ezrin表达水平与患者肿瘤转移与复发的关系

目的探讨胃癌组织中DLC-1和ezrin表达水平与胃癌转移或复发的关系。方法选择2005年9月至2010年12月行胃癌根治术并经病理确诊的患者160例。应用SP法检测DLC-1和ezrin在胃癌组织中的表达,采用COX回归模型探讨DLC-1和ezrin表达与肿瘤复发或转移的关系。结果正常胃组织细胞中,DLC-1表达水平较高,DLC-1免疫反应产物主要分布在细胞膜表面;胃癌癌旁组织中,DLC-1表达低于正常胃组织;在胃癌组织中,DLC-1表达低于癌旁组织。正常胃组织和癌旁组织中未见明显ezrin表达,但在胃癌细胞细胞核中,ezrin免疫组织化学染色较强,表达水平较高;胃癌组织中DLC-1表达与患者性别、年龄、术前CEA水平无明显关系,但DLC-1阴性表达患者与肿瘤LNR、肿瘤N分期成正相关,ezrin阳性表达患者术前CEA值、肿瘤N分期、LNR分期成正相关,LNR、DLC-1阴性、ezrin阳性是胃癌患者转移或复发的独立危险因素。结论 DLC-1表达阴性、ezrin阳性表达与增加胃癌的转移或复发的风险,是胃癌转移或复发的独立危险因素,参与肿瘤的发生发展。     

食蚁打洞说鲮鲤

穿山甲是国家二类保护动物。因其居于丘陵土穴之中,鳞色又如鲤鱼,故我国古代称之为鲮鲤。我国南方的广东、广西、贵州、云南、台湾、福建、浙江、安徽、湖南等省区均有分布,国外的印度尼西亚、越南、缅甸、尼泊尔等国亦产。在动物分类学上,穿山甲属于哺乳纲、鳞甲目、穿山甲科,是鳞甲目的唯一代表。它体圆腹大,身长一般约为40—55厘米;尾扁而粗,较体为短,     

内镜黏膜下剥离术和挖除术治疗上消化道肿瘤的疗效及安全性分析

目的:分析内镜黏膜下剥离术(ESD)和黏膜下挖除术(ESE)治疗上消化道肿瘤的疗效及安全性。方法:回顾性分析2017年1月至2019年4月我院消化内科接受ESD或ESE治疗的68例上消化道肿瘤住院患者的临床资料,收集患者基础疾病、手术时间、病变部位大小、整块切除率、并发症等资料,同时采用Logistic回归分析对术中穿孔进行危险因素分析。结果:64例患者完整切除瘤体(94.12%),肿瘤平均直径(16.98±8.29)mm。食管病灶病理类型以高级别上皮内瘤变为主,有15例(22.06%);胃部病灶分布以胃体、胃底和胃窦居多,分别有18例(26.47%)、16例(23.53%)和12例(17.65%),病理类型以间质瘤最多,占36.76%;11例患者发生并发症(16.18%),4例患者出现术后出血(5.88%),经过内镜下止血后好转,8例患术中穿孔(11.76%),均行内镜下尼龙绳联合钛夹行荷包缝合,其中1例患者术中穿孔合并术后迟发性出血;病灶最大直径(≥25 mm,P=0.036)和病灶部位(胃底,P=0.015)是导致ESD或ESE术中穿孔的独立危险因素。结论:ESD和ESE治疗上消化道肿瘤安全有效,但需注意病灶大小和胃底病变,因其是导致术中穿孔的独立危险因素。     

微卫星标记在穿山甲个体识别中的应用

在对非法走私和捕杀穿山甲的犯罪案件研究中,所涉及的穿山甲个体数量是量刑的重要依据,然而对于一些穿山甲鳞片、肉块及其深加工产品,从形态学上却无法进行个体识别。微卫星标记已证实是一种用于动物个体识别的可靠的遗传标记。本研究从已发表的34对穿山甲微卫星引物中筛选出6对多态性较高的引物,用于穿山甲鳞片的个体识别。结果表明:6个位点的观测值杂合度(Ho)为0.653-0.234;期望值杂合度(He)为0.926-0.861;MJA03的PIC最高(0.918),MJA13的PIC最低(0.852),平均PIC为0.884。单个座位的个体识别能力在0.826-0.956之间,累积个体识别能力为99.9999%,表明采用的6个位点适用于国内穿山甲走私案中的个体识别。     

穿山甲饲养方法探索

穿山甲(Manis pantadactyla)是我国鳞甲目动物唯一的代表。因食性特异,它的食物在人工饲养下难以满足,饲养寿命在我国很少有超过半年的。所以在动物园展出穿山甲也就不多。穿山甲的披鳞甲奇特的外形,特殊的食蚁习性以及它的经济意义,都是应该向人们介绍     

Stereotactic biopsy and cytological diagnosis of solid and cystic intracranial lesions

Cytological smears from 115 consecutive cases of stereotactic biopsies of intracranial lesions were reviewed. Ninety-five lesions were solid and 20 cystic. Material from 90 solid and 13 cystic lesions was sent both for cytological and histological examination. In 66 of the solid lesions, the cytological diagnosis was confirmed by histology (five were benign lesions and 61 malignant tumours: 56 primary brain tumours, three metastases and two lymphomas). In 24 cases with discrepant cytology and histology, the histology was inconclusive or insufficient in 14 cases, while cytology established the diagnosis of astrocytoma grade II (seven cases), metastases (two cases), gliosis (one case) and benign (four cases). Necrosis of tumour type was observed cytologically in six patients representing glioblastoma (two cases), anaplastic astrocytoma (one case), lymphoma (one case) and normal brain (two cases) histologically. Three cases reported cytologically as benign were primary brain tumour (two cases) and gliosis (one case). One smear of a glioblastoma was insufficient for cytological diagnosis. Cystic lesions were cytologically benign in 17 cases and malignant in three cases. Histology from the cyst wall confirmed the malignant diagnosis in three cases and showed tumour in six more cases, a benign process (two cases), changes induced by radiotherapy for arteriovenous malformation (one case) and insufficient material (one case). In conclusion, cytology from solid brain lesion allows an accurate diagnosis and subtyping of tumours in a majority of cases, and can thus be used to choose type of therapy. In cystic brain tumours, however, examination of the cystic fluid, is often inconclusive and a biopsy from the cyst wall should be performed if there is clinical or radiological suspicion of tumour.     

Endocrine profile in gastric carcinomas. An immunohistochemical study.

22 gastric carcinomas (13 intestinal type and nine diffuse type) were immunostained for neuron specific enolase, chromogranin, Leu-7 and a panel of fifteen different peptide hormones. Five out of the 13 tumours of intestinal type and four out of the nine diffuse carcinomas expressed immunoreactivity for one or more of the pan endocrine markers. Seven out of the 13 tumours of intestinal type and five out of the nine diffuse carcinomas also expressed immunoreactivity for gastrin (3), ACTH (3), serotonin (7) and calcitonin (7). Immunoreactivity for somatostatin (1) and substance P (1) were also seen in two tumours of intestinal type. Seven out of 18 cases with benign mucosa adjacent to the tumours expressed a focal immunoreactivity for chromogranin (6), serotonin (6), gastrin (5) and calcitonin (1). All hormone-producing tumours also expressed immunoreactivity for carcino-embryonic antigen. Our results confirm that a high proportion of gastric carcinomas are hormone producing.     

EGFR,HER-2 and KRAS in Canine Gastric Epithelial Tumors: A Potential Human Model?

Epidermal growth factor receptor (EGFR or HER-1) and its analog c-erbB-2 (HER-2) are protein tyrosine kinases correlated with prognosis and response to therapy in a variety of human cancers. KRAS mediates the transduction of signals between EGFR and the nucleus, and its mutation has been identified as a predictor of resistance to anti-EGFR drugs. In human oncology, the importance of the EGFR/HER-2/KRAS signalling pathway in gastric cancer is well established, and HER-2 testing is required before initiating therapy. Conversely, this pathway has never been investigated in canine gastric tumours. A total of 19 canine gastric epithelial neoplasms (5 adenomas and 14 carcinomas) were retrospectively evaluated for EGFR/HER-2 immunohistochemical expression and KRAS mutational status. Five (35.7%) carcinomas were classified as intestinal-type and 9 (64.3%) as diffuse-type. EGFR was overexpressed (≥1+) in 8 (42.1%) cases and HER-2 (3+) in 11 (57.9%) cases, regardless of tumour location or biological behaviour. The percentage of EGFR-positive tumours was significantly higher in the intestinal-type (80%) than in the diffuse-type (11.1%, p = 0.023). KRAS gene was wild type in 18 cases, whereas one mucinous carcinoma harboured a point mutation at codon 12 (G12R). EGFR and HER-2 may be promising prognostic and therapeutic targets in canine gastric epithelial neoplasms. The potential presence of KRAS mutation should be taken into account as a possible mechanism of drug resistance. Further studies are necessary to evaluate the role of dog as a model for human gastric cancer.     

Quantity of AgNORs in gastric endocrine carcinoid tumours as a potential prognostic tool

In order to assess if the quantity of silver-stained nucleolar organizer region (AgNOR) proteins represents a prognostic tool in gastric carcinoids, a standardised AgNOR analysis was performed on 24 samples collected from the pathology archives of the Universities of Messina and Parma; the samples were taken at surgery from 11 males and 13 females (mean age 55 yrs, age range 28-77 yrs); 13 cases were defined as Type I, 1 case as Type II and 10 cases as Type III; 16 cases showed a diameter <1 cm, 8 >1 cm. Only 6 tumours were deeply invasive, breaking through the muscularis propria or the subserosa. The proliferative status of carcinoids performed by Ki67 protein antibodies was available in 20/24 cases. The quantification of AgNORs was performed according to the guidelines of the Committee on AgNOR Quantification and the mean area (microm2) of AgNORs per nucleus (NORA) was determined by means of image analyser and specific software programs. The relationship between NORA values and Ki67 data was investigated by Spearman correlation test. The mean NORA value of all 24 gastric carcinoids was 1.279 microm2 (SD 0.404); values ranged from 0.734 to 2.142 microm2. A significantly higher (p < 0.001) mean NORA value (1.736 microm2; SD 0.283) was found in tumours larger than 1 cm, in comparison to the smaller neoplasms (1.051 microm2; SD 0.214); moreover, cases showing deep wall invasion exhibited a mean NORA value of 1.765 microm2 (SD 0.276), significantly higher (p < 0.001) than those with superficial growth (1.118 microm2; SD 0.296). Finally, a similar highly significant difference was seen between type III carcinoids (1.615 microm2; SD 0.375) and type I-II (1.040 microm2; SD 0.208). A linear relationship between Ki67 and corresponding NORA values was obtained by the Spearman correlation test (p = 0.001). No other significant correlations were found between mean NORA values and other clinico-pathological parameters. The AgNOR method seems to be an additional tool potentially able to predict the prognosis of this kind of endocrine tumour, facilitating the identification of fast-growing tumours and being able to directly correlate with the size, deep invasion of gastric wall and tumour type, generally considered as the best prognostic indicators.     

Anaplastic Lymphoma Kinase Rearrangement in Digestive Tract Cancer: Implication for Targeted Therapy in Chinese Population

Background

Anaplastic lymphoma kinase (ALK) rearrangements define a subgroup of lung cancer which is eligible to targeted kinase inhibition. The aim of this study is to observe the incidence rate of ALK fusion in a large cohort of Chinese digestive tract cancer patients.

Patients and Methods

Tissue microarray (TMA) was constructed from 808 digestive tract cancer cases, including 169 esophageal squamous cell carcinoma, 182 gastric cancer and 457 colorectal cancer (CRC) cases. We tested all cases for ALK expression via a fully automated immunohistochemistry (IHC) assay. The IHC-positive cases were subjected to fluorescence in situ hybridization (FISH), real-time polymerase chain reaction (qRT-PCR), target gene enrichment and sequencing for confirmation of ALK gene rearrangement and discovery of novel fusion partner.

Results

Among the tested cases, 2 (0.44%) CRC cases showed positive both by IHC and FISH. By qRT-PCR, EML4–ALK fusion was found in one IHC-positive CRC case. In another IHC-positive CRC case, target gene enrichment and sequencing revealed ALK was fused to a novel partner, spectrin beta non-erythrocytic 1 (SPTBN1). One gastric cancer case showed partially positive IHC result, but no fusion was found by FISH and gene sequencing.

Conclusions

The incidence rate of ALK gene fusion in Chinese CRC patients was 0.44%,but not detectable in gastric and esophageal cancers. The novel SPTBN1 -ALK fusion, together with other ALK fusion genes, may become a potential target for anti-ALK therapy.     

Evaluation of heterogeneity of DNA ploidy in early gastric cancers.

DNA ploidy has been shown to be a predictive parameter for prognosis in various solid tumours. The prognostic value of DNA-ploidy in gastric cancers is still a matter of controversy. A possible explanation for the discrepant results reported in the literature could be sampling error in tumours with multiple stemlines differing in DNA-ploidy. In order to determine whether or not such heterogeneity exists in early gastric carcinoma, we have performed DNA cytophotometry on multiple samples of a group of 17 early gastric carcinomas, of which 8 were pure intramucosal and 9 were infiltrating into the submucosa. We found an aneuploid DNA-stemline in 8 (47%) early gastric cancers, more often in tumours invading into the submucosa (5/9) than in purely mucosal tumours (3/8). Multiple DNA-stemlines were found more frequently in submucosally infiltrating tumours (4/5). These results confirm the presence of DNA-aneuploid early gastric carcinoma which are frequently heterogeneous and suggest that heterogeneity occurs more frequently in tumours invading the submucosa. This heterogeneity is best detected by analysing multiple samples of tumours for DNA-ploidy.     

Neural tumours of the neck presenting as thyroid nodules: a report of three cases

OBJECTIVES: Neural tumours of the neck may at times secondarily involve the thyroid and manifest clinically as thyroid nodules. On cytological evaluation these nodules may be confused with other spindle lesions of the thyroid. We report two cases of schwannoma and one case of a malignant peripheral nerve sheath tumour (MPNST) of the neck, which presented as thyroid nodules and evaluate the role of cytology in identifying these tumours. METHODS: The thyroid nodules in all the three cases were sampled by the non-aspiration technique using a 23-gauge needle. Both alcohol-fixed and air-dried smears were prepared and stained by the Papanicolaou and May-Grünwald-Giemsa stains. Cytology smears and histology sections from the resected specimens were reviewed, and the findings noted. RESULTS: Both the cases of schwannoma were correctly identified on cytology while the case of MPNST could only be typed as a spindle cell tumour. However, on cytology it was not possible to state whether the tumours were thyroidal or extrathyroidal in origin. CONCLUSIONS: Schwannomas of the neck are easily identifiable on cytology compared with MPNST. However, cytology alone is not helpful in identifying the origin of these tumours. As primary neural tumours of the thyroid are rare, the possibility of a soft tissue neural tumour extending into the thyroid should always be ruled out while evaluating these cases.     

Does Microhistology Improve the Cytological Diagnosis of Liver and Pancreatic Tumours?

Guided percutaneous fine needle aspiration cytodiagnosis of the liver, retroperitoneum and pancreas was performed in 197 patients. In 42 cases, material left after the smears were prepared was embedded in paraffin wax for histological examination. Six liver tumours and seven pancreatic tumours were identified in this material. In two cases the diagnosis of liver cell carcinoma was made only after microhistological examination. Re-examination of the cytological material in both cases disclosed features of liver cell carcinoma which were underestimated in the first examination and diagnosed only broadly as cancer cells. On the other hand, in another case cancer cells were present only in the smear and absent in the microhistological preparation. Diagnosis of pancreatic tumours was generally not improved by microhistological examination. In one case cancer cells were present only in the cytological material. In another case a cytological diagnosis of suspected cancer was confirmed as adenocarcinoma by microhistology. The diagnosis of non-neoplastic material in the remaining 29 cases were identical by cytopathology and microhistology. It is concluded that the microhistology of needle aspirate material complements cytological examination and can refine diagnosis although it increases cost.     

Dual tumours in the GI tract: synchronous and metachronous stromal (GIST) and epithelial/neuroendocrine neoplasms

Gastrointestinal stromal tumours (GIST) constitute the most frequent group of mesenchymal tumours in the gastrointestinal tract (GI). During the last several decades major advances have been taken in the diagnostics, treatment, and understanding of its pathogenesis. However, much less is known about the either metachronous or synchronous concurrence of GIST and other tumours of different histogenesis. In the present study clinicopathological data of 43 patients with histologically proved gastrointestinal stromal tumour were studied mainly in regard of the occurrence of a secondary neoplasm. Among the 43, 7 cases were found with secondary tumour mainly of epithelial origin. In three cases (cases 3, 5, and 7) GIST concurred with colorectal adenocarcinoma, in one case (case 1) GIST occurred in a patient with a 3-years-history of chronic lymphocytic leukaemia (CLL), in other two (cases 2 and 4) the stromal tumour was combined with in situ adenocarcinoma of the stomach and carcinoid of the pancreas, respectively. In case 6, GIST concurred with a duodenal Brunner gland adenoma. In five cases the stromal tumour and the other neoplasm occurred synchronously, and in four of them, being the stromal tumour clinically silent, GISTs were intraoperative findings. This confirms the importance of surgical intraabdominal control before closure. In one hand the repeated concurrence of GIST and colorectal adenocarcinoma in our series, and on the other hand, that of GIST and adenocarcinoma of the stomach in the literature, may indicate an at least partly common factor, which may be involved in the pathogenesis of these neoplasms.     

Sclerosing stromal tumour--a rare ovarian benign neoplasm: description of three cases

Sclerosing stromal tumour is a rare benign usually unilateral ovarian tumour. We present three cases of this neoplasm in young females, including one bilateral case. All tumours were composed of cellular areas forming pseudolobular patterns, as well as vascular, fibrous, and myxoid areas. The characteristic feature of tumours was cellular heterogenity. All tumours revealed negative immunostaining for cytokeratin, and intense positive immunostaining for vimentin, and smooth muscle actin. Immunostaining for desmin and progesterone receptors was weakly positive.