实验性大肠癌肠粘膜细胞增殖力学的变化规律及其意义

应用流式细胞光度术（ＦＣＭ）和银染核仁形成区（Ａｇ－ＮＯＲ）自动图像分析技术，对二甲基肼（ＤＭＨ）诱发Ｗｉｓｔａｒ大鼠大肠癌发生过程中的细胞增殖力学，进行了定量研究。结果表明，在注射ＤＭＨ第７、１４、２１和２８周时，肠粘膜增殖指数（ＰＩ）分别为１６．８３±１．８６、２４．２２±２６２９、２９．７０±７．１３和３１．８４±３．５５，均显著高于正常大鼠的１２．２０±２．６０（Ｐ＜０．０１）；Ａｇ一ＮＯＲ颗粒数在正常大鼠肠粘膜上皮细胞为３．６±０．７，而在上述诱癌不同时期则分别为５．７±ｌ．０、６．０±０．８、６．８±２．３和５．４±１．０（Ｐ＜０．０１）。这些变化不仅可作为大肠癌发生的早期生物学特征，而且还有助于确定实验动物的患癌易感程度。     

流式细胞光度术研究大鼠肝癌及癌前病变DNA的变化

目的用流式细胞光度术（ＦＣＭ）探讨大鼠肝癌和癌前病变ＤＮＡ变化的意义．方法取正常大鼠、肝硬变、非典型增生和肝癌大鼠肝脏组织块，制成单细胞悬液，做ＦＣＭ分析．结果从正常肝组织到肝脏的各级病变，二倍体细胞所占的百分比逐渐增加（７１０±２２，７５０±２８，７６０±４４，８００±３９，Ｐ＜００５），四倍体细胞百分比则下降（１５０±１４，１４０±１０，１２０±２４，９９±１７，Ｐ＜００５），Ｓ期比率（％）升高（８４±１４，１００±１０，１０８±２５，１１３±１８，Ｐ＜００５）．在肝癌大鼠中５０％为异倍体．结论ＦＣＭ分析对肝癌前病变及肝癌的早期诊断有一定的临床意义．     

如何减少大肠癌的误诊

目的探讨如何减少大肠癌的误诊。方法对１９７０年１月至１９９５年１２月在北京协和医院经手术病理确诊的大肠癌７９１例的诊断经验加以分析，其中结肠癌３９６例，直肠癌３９５例，年龄２０～８５岁，平均５４４岁。结果（１）本组大肠癌手术病例数逐年增多。（２）ＤｕｋｅｓＡ、Ｂ期占３６％，平均误诊时间４８个月，Ｃ、Ｄ期平均误诊时间８０个月。（３）以脓血便、便鲜血、腹痛伴包块、首发贫血及间断发热为临床重要表现者，分别占大肠癌的１５３％、１０２％、７６％、５４％及２０％。这些病人一度被误诊为细菌性痢疾、内痔、急慢性肠梗阻、贫血及肠结核等。（４）距肛门７ｃｍ以下的直肠癌占４２２％，却有７５１％的患者未做肛门指检。（５）粪潜血试验的阳性率为８４％，作１次试验的阳性率仅２０％，连续３次试验的阳性率为１００％。结论大肠癌的临床表现形式多样化，应提高警惕，粪潜血试验和直肠指诊是筛查的重要手段     

霉酚酸酯治疗顽固性Ⅳ型狼疮性肾炎

目的：观察新型免疫抑制剂霉酚酸酯（ＭＭＦ）治疗顽固性Ⅳ型狼疮性肾炎（ＬＮ）的疗效及副作用。方法：对传统免疫抑制剂治疗无效或复发的１７例Ⅳ型ＬＮ患者，改用ＭＭＦ联合小剂量糖皮质激素治疗。ＭＭＦ剂量０．７５～２．０ｇ／ｄ，治疗时间３～９（平均４．３５±１．５）个月。结果：经ＭＭＦ治疗后，５例肾功能不全（３例需透析）者３例血清肌酐恢复正常。８２．４％患者尿蛋白减少半量以上，其中２９．４％患者尿蛋白转阴。平均尿蛋白由３．５９±１．３９ｇ／ｄ降至１．１２±０．９７ｇ／ｄ，４１．２％患者的血尿消失，血清自身抗体产生明显减少，血清冷球蛋白水平由６０９．９±４３３ｍｇ／Ｌ降至１３２．４±７０．５ｍｇ／Ｌ。８例患者治疗３个月后行重复肾活检，肾小球活动性病变显著减轻，活动性指数由６．５±１．５降至１．２±０．７，免疫荧光检查发现ＭＭＦ治疗后肾小球内血管细胞粘附分子（ＶＣＡＭ）表达显著减少。副作用包括肺炎（１１．８％）、带状疱疹（１１．８％）、胃肠道反应（３５．３％），未见白细胞减少及肝功能异常。结论：ＭＭＦ对传统免疫抑制剂治疗无效的重症、难治性Ⅳ型ＬＮ有独特的疗效。尽管ＭＭＦ副作用小，但仍需注意感染合并症的发生     

157例大肠癌肠镜资料分析

我院自１９８３年至１９９６年１月共进行大肠镜检查３４４３例次，经内镜、病理和手术确诊为大肠癌１５７例，占同期受检人数的４．５６％，现报告并分析如下。１．性别与年龄：１５７例大肠癌中，男９０例，女６７例，年龄１５－８７岁，平均５７．３岁，其中＞５０岁１２５例，占７９．６％。２．受检时间：从出现症状至接受肠镜检查时间＜１个月１２例，１～３个月７７例，占４９．０％，４～６个月３８例，７－１２个月１６例，＞１２个月１４例。３．临床症状：鲜血便或脓血便９７例，占６１．８％；腹痛９０例，５７．３％；腹泻６４…     

原发性大肠恶性淋巴瘤临床、内镜与病理特点

目的 搪塞原发性大肠恶性淋巴瘤（ＰＣＭＬ）的临床表现、内镜和病理特点。方法 采用血常规及血型检测，Ｘ线检查、内镜检查，最终均得到手术和病理证实。结果 ２４例ＰＣＭＬ中临床表现以腹痛、体重下降、发热、腹块、便血和大便习惯改变为主。病变位迂回在盲部９例（３７．５％），直肠１例（４．２％）。内镜下表现为隆起９／１６例（５６．２％）、浸润型４／１６型（２５．０％），溃疡型３／１６例（１８．８％），与术后分     

78例老年人低位直肠癌手术疗效分析

目的探讨老年人低位直肠癌根治术低位吻合，以保留肛门功能的疗效。方法于癌灶上缘肠腔内及相应的动脉内分别注入５－氟尿嘧啶（５－Ｆｕ）０．７５及０．５ｇ，上、下肠管的切断处用５－Ｆｕ擦洗。切断直肠的长度距癌灶下缘３．０ｃｍ者１８例，３．５ｃｍ２４例，４．０ｃｍ３６例。清扫与癌灶相应的肠系膜及根部的淋巴结。结肠与直肠断端在肛门口外处吻合并回纳。结果术后每２年复查，局部复发６例。随访１、３、５、１０年生存率依次为９３．６％、８９．０％、８９．２％、５５．８％。结论老年人低位直肠癌根治保肛手术疗效可靠，是一种较佳术式。     

大肠癌及癌旁内分泌细胞的表达意义

目的探讨内分泌细胞（ＥＣ）在大肠癌及癌旁的表达意义．方法应用ＬＳＡＢ免疫组化法，对１１７例大肠癌及８５例癌旁粘膜中嗜铬蛋白Ａ（ＣＧＡ）及几种激素进行检测，１３例大肠癌行电镜观察．结果ＥＣ阳性大肠癌４６例（３９３％），检测到一种以上激素６９２％（２７／３９），癌旁粘膜ＥＣ数高于正常肠粘膜．电镜观察８例有含内分泌颗粒的癌性ＥＣ．在中低分化癌中ＥＣ（＋＋）的表达（２５５％）高于高分化癌（６９％）（χ２＝７５４，Ｐ＜００５），含有ＥＣ的大肠癌淋巴结转移的发生率（６８０％）高于不含ＥＣ者（４３７％）（χ２＝６２３，Ｐ＜００５），且预后不良；５ＨＴ，βＨＣＧ，Ｇｌｕ，Ｇａｓ阳性癌分化及预后较差（Ｐ＞００５）．结论含ＥＣ的大肠癌具有更恶性的生物学行为，可能与ＥＣ中某些激素，通过旁分泌等途径促进肿瘤的生长转移有关，癌旁ＥＣ增生与周围肿瘤生长有关．     

腹主动脉结扎大鼠心房纤维化的实验研究

高血压患者有较高心律失常的发生率，房性心律失常可能与左房扩大或心房纤维化有关。为观察压力负荷增高大鼠中心房纤维化的发生情况，将Ｗｉｓｔａｒ大鼠随机分成假手术组和手术组，手术组大鼠行肾上腹主动脉部分结扎。术后４，８，１２周分别测定大鼠颈动脉压及心房胶原容积分数（ＣＶＦ），结果发现：①手术组左室舒张压明显高于假手术组（４，８，１２周分别为１８．５±２．５ｋＰａｖｓ１５．７±１．９ｋＰａ，１８．６±２．７ｋＰａｖｓ１５．３±１．３ｋＰａ，１９．６±３．１ｋＰａｖｓ１５．２±１．９ｋＰａ，Ｐ＜０．０５或０．０１）。②手术组心房ＣＶＦ明显高于假手术组（４，８，１２周左、右房分别比较：４．２３±０．７６％ｖｓ２．９３±０．８７％，４．６５±１．４５％ｖｓ３．１１±１．０７％，５．６２±１．６２％ｖｓ３．２３±１．２８％；３．８８±１．１５％ｖｓ２．５１±０．８４％，４．２４±１．６５％ｖｓ２．５１±０．８４％，５．３４±１．３２％ｖｓ２．３３±１．１４％；Ｐ＜０．０５或０．０１），手术组心房ＣＶＦ有逐渐上升趋势。③左房ＣＶＦ与左室舒张压之间无直线相关关系（ｒ＝０．１６９１，Ｐ＞０．０５）。提示在高血压大鼠模型中存在心房?     

胃癌组织nm23和c-erbB_2癌基因蛋白表达与根治术后再发癌的关系

目的探讨ｎｍ２３和ｃｅｒｂＢ２癌基因蛋白表达与胃癌根治术后再发癌发生的关系．方法采用免疫组化ＳＰ法检测６４例胃癌中ｎｍ２３和ｃｅｒｂＢ２的表达，并结合内镜及随访资料进行分析．结果胃癌ｎｍ２３低表达率及ｃｅｒｂＢ２阳性率在淋巴结转移组及术后３ａ内有再发癌组明显增高，ｎｍ２３低表达率及ｃｅｒｂＢ２阳性率：有淋巴结转移组为６８９％（３１／４５）和４２２％（１９／４５）；无淋巴结转移组为３６８％（７／１９）和１５８％（３／１９）；术后３ａ内再发癌组为８１０％（１７／２１）和５２４％（１１／２１）；术后３ａ以上无再发癌组为４８８％（２１／４３）和２２６％（１１／４３）（Ｐ＜００５）．而且ｎｍ２３低表达与肿瘤浸润程度有关，浸至浆膜及周围脏器组ｎｍ２３低表达率为７８６％（２２／２８）；浸至粘膜及粘膜下组者为４００％（６／１５）（Ｐ＜００５）．结论胃癌ｎｍ２３低表达和ｃｅｒｂＢ２阳性表达者具有较强的浸润、转移能力，且术后易发生再发癌，二者的表达变化对判断胃癌术后再发癌的发生及预后有重要意义     

CpG island methylation as an early event during adenoma progression in carcinogenesis of sporadic colorectal cancer

BACKGROUND AND AIMS: CpG island methylation is present in various tumors, including colorectal carcinomas, and is thought to be an important mechanism in carcinogenesis. We evaluated the methylation status of primary colorectal tumors to determine its role in the adenoma to carcinoma sequence. METHODS: The methylation status of APC, THBS1, MGMT, hMLH1 and GSTP1, as determined by methylation specific PCR (MSP), and microsatellite instability (MSI) using three mononucleotide markers were assessed in 40 colorectal adenomas and 36 adenocarcinomas. The correlations of methylation status and MSI with the clinicopathologic parameters of the tumors were determined. RESULTS: Of the 40 adenomas, 24 (60%) were methylated at one or more loci, and 12 (30%) at two or more loci (CpG island methylation phenotype-high, CIMP-H). Of 36 carcinomas, 27 (75%) were methylated at one or more loci and 11 (30.5%) at two or more loci (CIMP-H). THBSI was the most frequently methylated locus in both adenomas (n = 19, 47.5%) and carcinomas (n = 16, 44.4%). Overall, methylation status of adenomas and carcinomas did not differ significantly (P = 0.53), nor did the methylation status of individual genes. For adenomas, size (P = 0.049) and histologic classification of the villous components (P = 0.018) were each associated with methylation status. For carcinomas, however, no clinicopathologic variable was related to methylation status. MSI was detected in three adenomas (7.5%) and five carcinomas (13.9%), and was closely correlated with hMLH1 methylation (P < 0.001). CONCLUSIONS: In colorectal tumors, CpG island methylation of tumor suppressor genes appears to be common and may be involved in the progression of adenomas.     

Synchronous primary adenocarcinomas of the colon and rectum

Summary In a series of 1,002 cases of primary colorectal adenocarcinomas diagnosed during a ten-year period there were 62 (6.2 per cent) patients who had two or more primary colorectal adenocarcinomas. Most of the tumors were more than 5 cm away from each other: 27 carcinomas were separated by 6–10 cm, 16 were separated by 11–20 cm, and 12 were separated by more than 20 cm. It is concluded that the incidence of synchronous carcinomas of the colon is sufficiently high to warrant a search by both surgeon and endoscopist for additional tumors some distance from the initial lesion.     

Expression of pituitary tumor transforming gene in human gastric carcinoma

AIM: Pituitary tumor transforming gene (PTTG1) is overexpressed in a variety of tumors, including carcinomas of the lung, breast, colon, as well as in leukemia, lymphoma and pituitary adenomas. However, there is little information on its expression in gastric carcinoma. We sought to investigate the expression of PTTG1 in gastric carcinoma and to explore the relationship between its expression and clinicopathological factors. METHODS: We studied 75 primary human gastric adenocarcinomas, including 17 mucosal carcinomas, 21 submucosal infiltrative carcinomas, 12 carcinomas invading proprial muscle layers, 6 carcinomas reaching the subserosa, and 19 carcinomas penetrating the serosal surface. Immunohistochemical analysis was performed using paraffin-embedded sections of gastric adenocarcinomas. RESULTS: PTTG1 was expressed heterogeneously in carcinomas. Positive PTTG1 staining was observed in 65.3% of the carcinomas (49 of 75). Its expression did not correlate significantly with either the histological type or the depth of infiltration of the gastric carcinomas. However, a statistical analysis showed significant differences between the primary adenocarcinomas and the associated metastatic lymph nodes. CONCLUSION: The results of this study demonstrate that PTTG1 expression is enhanced in metastatic lymph nodes in comparison to that in primary carcinomas. We suggest that PTTG1 may contribute to lymph node metastases in gastric carcinoma.     

Distinct relationship between polypoid growth type and sporadic colorectal carcinomas with microsatellite instability.

BACKGROUND/AIMS: This study was carried out to clarify whether colorectal carcinomas with MSI (microsatellite instability) is correlated with growth types of invasive carcinomas. METHODOLOGY: Samples of tumor tissue and adjacent normal mucosa were obtained from 45 patients with sporadic advanced colorectal cancer. The MSI was assessed by the mobility shift assay of microsatellite and VNTR (variable numbers of tandem repeat) alleles using 12 markers. Tumors with four or more positive loci were determined to be MSI positive. The polyadenine tract (A)10 of the third exon in TGF beta RII was also assessed by mobility shift assay of DNA fragments amplified with primers. Histological examination was performed to divide all tumors into polypoid growth carcinoma and nonpolypoid growth carcinoma, according to Shimoda et al.'s classification. RESULTS: Ten of 11 cases with MSI had a 1-base pair deletion in a polyadenine tract in the TGF beta RII gene. Fifteen cases showed polypoid growth and 30 cases indicated nonpolypoid growth. There were 9 polypoid growth cases and 2 nonpolypoid growth cases with MSI, while there were 6 polypoid growth cases and 28 nonpolypoid growth cases without MSI. Colorectal cancer cases with MSI had a significantly higher incidence of cases with polypoid growth (9/11) compared to those without MSI (6/34) (P = 0.0004). CONCLUSIONS: Sporadic colorectal carcinomas with MSI tend to show a polypoid growth type. We think that there are two types including "adenoma-carcinoma sequence" type and "RER" type in colorectal carcinomas that show adenoma-carcinoma progression.     

Adenoma and Carcinoma of the Duodenum and Papilla of Vater: A Clinicopathologic Study

In a retrospective study (1982-1990), 12 adenomas, 35 carcinomas of the papilla of Vater, and 21 duodenal adenomas were examined. All patients had endoscopicbioptic examinations (5-10 forceps biopsies, snare biopsy or forceps-biopsies after endoscopic sphincterotomy). Special attention was paid to malignant transformation of adenomas and of residual adenomatous tissue in surgical resected cancer. Follow-up data were gained by reexamination or questionnaires. In papillary adenomas, an adenocarcinoma was found in 30% at operation or by follow-up. In 41.2% of the operated cases, residual adenomatous tissue was found, more often in well-differentiated adenocarcinomas than in other histological types. A transformation from duodenal adenomas to adenocarcinomas was seen less frequently (9.5%). Therefore, the risk of malignancy in ampullary adenomas is greater than elsewhere in the duodenum. In eight of 11 patients (72.7%) with duodenal adenomas, one or more simultaneously developed colonic adenomas were found (in four cases a Gardner syndrome not known before). We conclude that there is strong evidence that most ampullary and duodenal carcinomas develop in preexisting adenomas, with an adenoma-cancer sequence similar to that accepted for colorectal carcinoma. This has to be kept in mind for diagnostic as well as therapeutic reasons. When either an adenoma of the ampulla or duodenum is diagnosed, colonoscopy is mandatory to find or exclude colonic adenomas. In patients with familiar adenomatosis, the duodenum and the papilla of Vater have to be examined endoscopically.     

Cyclo-oxygenase-2 and p53 immunoreactivity in superficial early colorectal carcinoma]

BACKGROUND/AIMS: De novo colorectal carcinoma shows more aggressive behavior including submucosal invasiveness. Both p53 and cyclo-oxygenase-2 (COX-2) have been shown to be involved in colon carcinogenesis, progression from adenoma to carcinoma, and submucosal invasion by tumor. We performed this study to evaluate the expression of p53 and COX-2 protein in de novo carcinoma, compared with ex-adenoma carcinoma. METHODS: Twenty three flat adenomas, 19 ex-adenoma carcinomas, 6 de novo carcinomas were included in this study. The expression of p53, COX-2 and Ki-67 were examined immunohistochemically. RESULTS: Both ex- adenoma carcinomas and de novo carcinomas showed similar size and shape. Positive staining for p53 was detected in 3 of 23 (13%) flat adenomas, in 11 of 19 (57.8%) ex-adenoma carcinomas (p < 0.05), and in 1 of 6 (16.6%) de novo carcinomas. Increased numbers of COX-2 positive tumor cells were observed in 1 of 23 (4.3%) flat adenomas, in 2 of 19 (10.5%) ex-adenoma carcinomas, and in 3 of 6 (50%) de novo carcinomas. COX-2 positive expression showed increased tendency in de novo carcinoma (p = 0.073). There was no correlation between COX-2, p53, and Ki-67 expression. CONCLUSION: De novo carcinoma shows increased tendency of COX-2 expression, but decreased p53 expression when compared to ex-adenoma carcinoma. These immunohistochemical findings are in accordance with the fact that de novo carcinoma has no preceding adenoma, with more frequent submucosal invasion despite the small lesion size.     

Differential DNA sequence deletions from chromosomes 3, 11, 13, and 17 in squamous-cell carcinoma, large-cell carcinoma, and adenocarcinoma of the human lung.

Activation of protooncogenes and inactivation of putative tumor suppressor genes are genetic lesions considered to be important in lung carcinogenesis. Fifty-four cases of non-small-cell lung cancer (23 adenocarcinomas, 23 squamous-cell carcinomas, and 8 large-cell carcinomas) were examined for loss of DNA sequences at 13 polymorphic genetic loci. Loss of heterozygosity was seen more frequently in squamous-cell carcinoma than in adenocarcinoma. The loss of DNA sequences from the short arm of chromosome 17 (D17S1 locus) was detected in 8 of 9 heterozygous cases of squamous-cell carcinoma and in only 2 of 11 heterozygous cases of adenocarcinomas. Furthermore, in 7 of these 8 squamous-cell carcinomas, loss of heterozygosity from chromosome 17 was accompanied by loss of DNA sequences from chromosome 11. The spectrum of allelic sequences lost from chromosome 11 was, however, similar in every type of carcinoma studied, and the data show two regions commonly deleted from chromosome 11 (11pter-p15.5 and 11p13-q13) that may have a role in the pathogenesis of all these types of non-small-cell bronchogenic carcinoma. Loss of DNA sequences from chromosome 3 was seen in 16 of 31 cases where the constitutive DNA was heterozygous-i.e., informative. These data included only 6 of 16 cases where loss of heterozygosity involved a chromosomal locus previously shown to be lost consistently in small-cell lung cancer (DNF15S2). Loss of heterozygosity at the chromosome 13q locus, D13S3, was seen in 9 of 21 informative cases, and in 2 cases, both adenocarcinomas, duplication of the intact DNA sequences suggested the possibility that mitotic recombination had occurred. Frequent DNA sequence deletions, including those from chromosome 17, in squamous-cell carcinomas may reflect the extensive mutagenic and clastogenic effects of tobacco smoke that may lead to inactivation of putative tumor-suppressor genes.     

Clinicopathologic characteristics of colorectal neuroendocrine tumor]

BACKGROUND/AIMS: Colorectal neuroendocrine carcinoma is a rare neoplasm exhibiting fulminant progression and having poor prognosis. The purpose of this study is to verify the clinicopathologic characteristics of colorectal neuroendocrine carcinoma. METHODS: From June 1997 to December 2004 at Asan Medical Center, ten patients were originally identified as colorectal neuroendocrine carcinoma on the basis of H&E and immunohistochemical staining (IHC). Carcinoid tumors were excluded in this study. Medical records of thirteen patients were reviewed retrospectively. RESULTS: Ten patients (0.2%) with colorectal neuroendocrine tumors were identified from 4,512 patients with colorectal cancer; ten neuroendocrine carcinomas and three adenocarcinomas with neuroendocrine differentiation. Their median age was 60 (41-83) years. The subjects consisted of six males and seven females. Nine tumors were located in the rectum, two in the sigmoid, and each one in the transverse colon and cecum, respectively. Nine of ten neuroendocrine carcinomas expressed synaptophysin, but chromogranin A were expressed in four. All patients were advanced at the time of diagnosis, with AJCC TNM staging: stage IIIB (n=2), stage IIIC (n=3), and stage IV (n=8). The median survival for ten neuroendocrine carcinomas and three adenocarcinomas with neuroendocrine differentiation were 16.4 months and 30 months, respectively. Five patients who received chemotherapy showed median survival of 32 months (stage III) and 17.5 months (stage IV), whereas other five patients without chemotherapy died with a median survival of 6.2 months. CONCLUSIONS: Colorectal neuroendocrine tumors are extremely rare showing aggressive behavior biologically, i.e fulminant early distant metastasis. Nevertheless, improved survival may be achieved by aggressive multimodality therapy.