胰腺上皮内瘤变

近年来，人们对胰腺上皮内瘤变(或称胰腺上皮内肿瘤，pancreatic intraepithelial neoplasia，PanIN)的认识有了较大的进展，1999年世界胰腺癌论坛大会提出的新分类和病理诊断标准^[1]，已逐渐为各国所采纳。越来越多的证据，特别是遗传学研究成果支持胰腺上皮内瘤变的新分类和分级系统^[2-5]，作为胰     

胰腺上皮内瘤变

一、PanIN的概念“胰腺上皮内瘤变”(PanINs)的概念在1994年被首次提出,1999年美国国立癌症研究所主持的胰腺癌论坛上得到了进一步明确,2002年在日本召开的胰腺原位癌论坛上病理学家对PanINs的概念进行了完善,2003美国Johns HopkinsHospital完整提出了PanINs的分级诊断标准(表1     

胰腺上皮内瘤变研究进展

胰腺癌恶性程度高,早期诊断困难,预后差.胰腺上皮内瘤变（PanIN）是胰腺导管腺癌（PDAC）最常见的非侵袭性前体病变.深入认识PanIN,能为在进展至侵袭性PDAC之前早期检出PanIN以及寻找有效治疗手段提供依据.本文对PanIN的临床、病理特征和遗传学改变作一综述.     

胰腺高级别上皮内瘤变及其miRNA的研究进展

胰腺上皮内瘤变（pancreatic intraepithelial neoplasia,PanIN）是指胰腺中小导管上皮细胞从不典型增生至原位癌这一系列病变的连续过程,根据其组织学异型性可分为3期,其中PanIN-1、2期为低级别,PanIN-3期为高级别[1-3].目前已经证实PanIN-3期是胰腺癌最直接的癌前病变[4].如果能在该期作出诊断,及时进行干预和治疗,是完全可以治愈胰腺癌的.因此寻找此期的特异性标志物是解决问题的关键.近年研究表明,miRNA不仅在肿瘤组织和细胞中的表达具有显著的肿瘤相关性、组织特异性和表达稳定性[5],而且在外周血中的表达同样具有肿瘤相关性和组织特异性,与RNA比较,其表达稳定性更为显著,因此认为外周血miRNA可能是一种理想的肿瘤分子标志物.同样,胰液中miRNAs检测也是早期诊断胰腺疾病的重要途径[6].因此,筛查和鉴定PanIN-3期组织和血或胰液中特异表达的miRNAs,探讨其作为胰腺癌早期诊断分子标志物的潜在可能性,对于提高胰腺癌的早期诊断率,改善其预后具有非常重要的意义.     

胰腺导管腺癌、慢性胰腺炎及正常胰腺组织中胰腺上皮内瘤变的比较研究

目的探讨胰腺导管腺癌、慢性胰腺炎和正常胰腺组织中各级别PanIN的发生率以及与临床病理学参数间的关系。方法回顾性研究长海医院2001年1月-2003年12月间外科切除和同期尸检获得的250例胰腺标本中PanIN的发生情况,并联系临床病理指标进行相关分析。结果250例胰腺标本中,有156例存在PanIN病变,发生率62.4％。其中,胰腺导管腺癌、慢性胰腺炎和正常胰腺组织中PanIN的发生率分别为75.6％、46.0％和30.0％,胰腺导管腺癌PanIN发生率明显高于慢性胰腺炎及正常胰腺组织(P<0.01);慢性胰腺炎中高级别PanIN发生率明显高于正常胰腺组织(P<0.05)。PanIN-3仅在胰腺导管腺癌和慢性胰腺炎中见到。胰腺导管腺癌中,有烟酒嗜好和(或)糖尿病者高级别PanIN的发生率53.7％,明显高于对照组29.4％(P<0.01)。PanIN的发生率以61-70岁年龄组为最高。结论胰腺导管腺癌、慢性胰腺炎和正常胰腺组织中PanIN的发生率逐渐增加,程度逐渐加重,支持胰腺癌发生的分子模型。     

胰腺腺鳞癌研究进展

胰腺腺鳞癌（adenosquamouscarcinoma,ASC）又称胰腺黏液表皮样癌（mucoepidermoidcarcinoma）、胰腺棘皮癌（adenoacanthoma）,是一种临床罕见的胰腺外分泌肿瘤,约占胰腺恶性肿瘤的2．1％,恶性程度高,预后很差。病理学上肿瘤由导管腺癌成分和鳞状细胞癌成分混合构成,临床表现与胰腺导管腺癌类似,术前确诊较困难,     

胰腺导管腺癌、慢性胰腺炎及正常胰腺组织中胰腺上皮内瘤变的比较研究

目的探讨胰腺导管腺癌、慢性胰腺炎和正常胰腺组织中各级别PanIN的发生率以及与临床病理学参数间的关系.方法回顾性研究长海医院2001年1月～ 2003年12月间外科切除和同期尸检获得的250例胰腺标本中PanIN的发生情况,并联系临床病理指标进行相关分析.结果 250例胰腺标本中,有156例存在PanIN病变,发生率62.4%.其中,胰腺导管腺癌、慢性胰腺炎和正常胰腺组织中PanIN的发生率分别为75.6%、46.0%和30.0%,胰腺导管腺癌PanIN发生率明显高于慢性胰腺炎及正常胰腺组织(P < 0.01);慢性胰腺炎中高级别PanIN发生率明显高于正常胰腺组织(P < 0.05).PanIN-3仅在胰腺导管腺癌和慢性胰腺炎中见到.胰腺导管腺癌中,有烟酒嗜好和(或)糖尿病者高级别PanIN的发生率53.7%,明显高于对照组29.4%(P < 0.01).PanIN的发生率以61 ～ 70岁年龄组为最高.结论胰腺导管腺癌、慢性胰腺炎和正常胰腺组织中PanIN的发生率逐渐增加,程度逐渐加重,支持胰腺癌发生的分子模型.     

淋巴上皮瘤样癌分子病理研究进展

淋巴上皮瘤样癌(LELC)是一组少见的与病毒感染密切相关的上皮性恶性肿瘤,可发生于全身任何器官.由于发病率低,LELC大样本临床研究缺乏,其发生的病因、发病机制、临床病理及分子病理特点尚不明确.该文就上述几方面进行文献综述,以期能够更好地了解LELC的发病及分子病理特征.     

胃黏膜上皮内瘤变的研究进展

胃癌是一种全球高发的消化系恶性肿瘤,早期胃癌的诊断是胃癌防治的要点.而胃黏膜上皮内瘤变作为胃癌的癌前病变始终是国内外研究的焦点.为了探索二者之间的关系,近年来,胃黏膜上皮内瘤变的相关领域、诸多方面都有较多研究进展,包括分子遗传学水平相关基因、癌基因改变;在临床处理方面的根除幽门螺杆菌(Helicobacter pylori,H.pylori)、定期随访和内镜治疗等,这些都为今后的临床工作带来一定的指导意义.但对胃黏膜上皮内瘤变的产生、影响因素和怎样演变为胃癌仍存在着很大疑问和未知领域,这需要进行大量多中心、较长期、前瞻性的设计研究.     

Hedgehog信号通路在胰腺上皮内瘤变恶性转化中的作用

胰腺上皮内瘤变（PanlN）是近年提出的新术语,是胰腺癌的癌前病变,K．ras高频突变是其重要特征之一。最近研究表明Hedgehog（Hh）信号转导通路早期异常激活在PanIN的发生和恶性转化中发挥重要作用。此外肿瘤干细胞增殖以及活性维持可能亦依赖于此信号通路。本文就Hh信号转导通路在PanlN的发生以及致瘤中的作用及其相关治疗作一综述。     

Proteomic analysis of pancreatic intraepithelial neoplasia and pancreatic carcinoma in rat models

AIM:To detect the proteomic variabilities of pancreatic intraepithelial neoplasia(PanIN)and pancreatic carcinoma(PC)induced by 7,12-dimethylbenzanthracene(DMBA) in rat models and to identify potential biomarkers.METHODS:Sixty adult male Sprague Dawley rats were randomized into three groups.The rats had DMBA implanted into their pancreas for one(n=20)or two months(n=20)or assigned to the normal group(n =20).The rats were killed after one or two months,and were evaluated histopathologically.Three tissue sampl...     

High-grade pancreatic intraepithelial lesions: prevalence and implications in pancreatic neoplasia

BACKGROUND: High-grade pancreatic intraepithelial neoplasia(Pan IN-3), a precursor of pancreatic ductal adenocarcinoma(PDAC), is not universally detected in resected pancreatic neoplasms. We sought to determine the prevalence and prognostic relevance of Pan IN-3 lesions in primary surgical resections of PDACs and intraductal papillary mucinous neoplasms(IPMNs).METHODS: A retrospective review of a tertiary care center pathology database(1/2000-6/2014) was performed. Demographics, imaging, pathology, disease-recurrence, and survival data were reviewed.RESULTS: A total of 458 patients who underwent primary pancreatic resection were included. "Pan IN-3" lesions were found in 74(16.2%) patients who either had PDAC(n=67) or main duct(MD)-IPMN(n=7). Among IPMN-MDs, Pan IN-3 lesions were exclusively found in those with pathological evidence of chronic pancreatitis. For PDACs, the median overall survival(OS) for pancreata with Pan IN-3 lesions was significantly better than those without(OS 1.12 years, interquartile range [IQR] 0.72, 2.05 years vs OS 0.86 years, IQR 0.64,1.60 years respectively; P=0.04). Multivariate Cox regression analysis demonstrated that the presence of Pan IN-3 lesions was associated with a reduced risk of death(HR=0.43; 95% CI: 0.23-0.82; P=0.01).CONCLUSIONS: Following primary resection of pancreatic adenocarcinoma, the lower survival observed in patients without Pan IN-3 lesions might suggest a state of complete or accelerated transformation. Further investigations are necessary to validate these findings that might impact disease prognosis and management.     

Progression to pancreatic ductal adenocarcinoma from pancreatic intraepithelial neoplasia: Results of a simulation model

Objectives

To gain insight into the natural history and carcinogenesis pathway of Pancreatic Intraepithelial Neoplasia (PanIN) lesions by building a calibrated simulation model of PanIN progression to pancreatic ductal adenocarcinoma (PDAC)

Chromoscopy-guided endomicroscopy increases the diagnostic yield of intraepithelial neoplasia in ulcerative colitis

BACKGROUND AND AIMS: Because of the large number of biopsy specimens, surveillance colonoscopy in ulcerative colitis (UC) is currently time consuming and significant flat lesions still may be missed. In this study we assessed the value of combined chromoscopy and endomicroscopy for the diagnosis of intraepithelial neoplasias in a randomized controlled trial. METHODS: A total of 161 patients with long-term UC in clinical remission were randomized at a 1:1 ratio to undergo conventional colonoscopy or chromoscopy with endomicroscopy. Eight patients were excluded because of insufficient bowel preparation. In the conventional colonoscopic group (n = 73), random biopsy examinations and targeted biopsy examinations were performed. In the endomicroscopy group (n = 80), circumscribed mucosal lesions were identified by chromoscopy and evaluated for targeted biopsy examination by endomicroscopy. The primary outcome analysis was based on the detection of neoplasias. RESULTS: By using chromoscopy with endomicroscopy, 4.75-fold more neoplasias could be detected (P = .005) than with conventional colonoscopy, although 50% fewer biopsy specimens (P = .008) were required. If only circumscribed lesions would have been biopsied in the first group, the total number of biopsy specimens could have been reduced by more than 90%. A total of 5580 confocal endomicroscopic images from 134 circumscribed lesions were compared with histologic results. The presence of neoplastic changes could be predicted by endomicroscopy with high accuracy (sensitivity, 94.7%; specificity, 98.3%; accuracy, 97.8%). CONCLUSIONS: Endomicroscopy based on in vivo histology can determine if UC lesions identified by chromoscopy should undergo biopsy examination, thereby increasing the diagnostic yield and reducing the need for biopsy examinations. Thus, chromoscopy-guided endomicroscopy may lead to significant improvements in the clinical management of UC.     

Low-dose radiation therapy for testicular intraepithelial neoplasia

Four patients with unilateral testicular germ-cell tumor and biopsy-proven contralateral testicular intraepithelial neoplasia (TIN; so-called carcinoma in situ) received localized low-dose radiation therapy (18–20 Gy) of the testis with TIN. Repeated biopsies disclosed the disappearance of TIN and germ cells. No recurrence of TIN or germ cells was observed after a follow-up of 18–42 months. All patients reported a normal sex life without need of androgen supplementation. Serum follicle-stimulating hormone increased significantly immediately after radiation treatment and started to decline after 24 months. Serum luteinizing hormone increased slightly but not significantly. A decline after 24 months was observed in only one of three patients. Serum testosterone decreased significantly in all patients after 1 year but never became subnormal. Low-dose radiation treatment is efficacious in eradicating testicular intraepithelial neoplasia without destroying Leydig cells or stromal cells of the testis. Thus, a patient otherwise destined to develop a second testicular tumor can be spared orchiectomy and life-long hormonal replacement.     

结直肠高级别上皮内瘤变的处理策略

[目的]研究结直肠高级别上皮内瘤变的临床及病理特征,探讨外科治疗原则和策略。[方法]45例结直肠肿瘤患者术前经内镜病理活检均诊断为高级别上皮内瘤变者,其中1例行腹腔镜探查,2例扩肛肿瘤局部切除,1例扩肛局部切除后补充行Miles术,2例行姑息性肿瘤手术,余39例行根治性结直肠癌手术,并将手术标本与术前病理作比较。[结果]术后病理活检示45例中有3例仍为高级别上皮内瘤变;42例证实为腺癌,其中1例伴有肝转移,24例有淋巴结转移,17例无淋巴结转移。[结论]术前病理活检确诊的结直肠高级别上皮内瘤变的肿瘤与术后病理活检结果一致性较差,对于这类患者应予积极的外科处理。     

False-negative biopsy for testicular intraepithelial neoplasia

Summary A routine biopsy of the contralateral testis obtained during orchiectomy for embryonal carcinoma in a 26-year-old patient was negative for testicular intraepithelial neoplasia (TIN; carcinoma in situ of the testis). However, a rebiopsy that was taken because of unexplained elevation of -fetoprotein 15 months later proved to be positive for TIN. Six previously reported cases of false-negative testicular biopsies obtained during a search for TIN are reviewed. In the light of several thousands of biopsies performed world-wide to date, the number of false-negative biopsies is probably very low. Although TIN is obviously not randomly dispersed throughout the testis in all patients, a routine biopsy of the contralateral testicle in patients with testis cancer remains a valuable tool for early detection of bilateral testicular tumorscal distribution of TIN in testes removed for this lesion. Their results suggested that after puberty TIN is usually randomly dispersed throughout the testicle. Support for this concept was recently given by Mumperow et al. (1992). These authors examined tumor-bearing testes and they did not find differences in the presence of TIN in biopsies taken from a location close to the tumor and taken from a location distant from the tumor. Thus, one single biopsy is regarded to be representative for the entire testis and one biopsy taken after puberty is also assumed to be reliable for predicting whether the testis will ever develop cancer (Berthelsen and Skakkebaek 1981 a). Conversely, if the biopsy is negative for TIN, a future tumor manifestation in the testicle examined is not expected according to this theory (Skakkebaek et al. 1987). Taken together, the concept of TIN would constitute an ideal avenue for the early detection of testis cancer in high-risk populations with the biopsy being a safe means of discriminating between individuals who will or who will not develop testis cancer.Abbreviation TIN testicular intraepithelial neoplasia     

胃上皮内瘤变术前活检与内镜黏膜下剥离术后病理差异性的探讨

目的对胃黏膜上皮内瘤变术前活检与内镜黏膜下剥离术(ESD)后出现病理差异这一现象进行探讨,并分析导致这种差异的原因以及相关影响因素。 方法回顾性分析了2016年7月至2019年6月经江苏省中医院住院行ESD治疗、术前活检为低级别上皮内瘤变(LGIN)/高级别上皮内瘤变(HGIN)的342例患者资料,运用统计学方法分析导致差异的影响因素。 结果342例患者中,187例为LGIN、155例为HGIN。LGIN组中病理一致者占61.5%,升级为HGIN、早期胃癌及以上者分别为21.4%、12.8%,总升级率34.2%,降级为慢性炎症者4.3%。HGIN组病理维持一致者占40.6%,升级为早期胃癌及以上者占52.9%,降级为LGIN者6.5%。多因素回归分析结果显示：病灶位于胃上1/3、表面充血、结节、放大内镜下DL(＋)、MV(＋)是LGIN组病理升级的危险因素;病灶表面结节是HGIN病理升级的危险因素。 结论白光内镜下活检与ESD后病理存在差异,病灶在胃上1/3、表面充血、结节、DL(＋)、MV(＋)是LGIN病理升级的危险因素;病灶表面结节是HGIN病理升级的危险因素。     

胃黏膜低级别上皮内瘤变及早期胃癌活检病理与术后病理差异的危险因素分析

【摘要】 目的 探讨胃黏膜低级别上皮内瘤变及早期胃癌活检病理与术后病理差异的危险因素。方法 回顾性分析行内镜黏膜下剥离术或手术切除,且术后病理诊断为低级别上皮内瘤变或早期胃癌（包括高级别上皮内瘤变）的235例患者资料,按活检病理与术后病理是否有显著差异分组,采用单因素和多因素分析探索病理结果发生显著差异的危险因素。结果 235例患者中33例（14.0%）发生病理显著差异。单因素分析结果提示,隆起型病变、病变表面不发红、病变不伴糜烂或溃疡、组织学类型为弥散型及活检块数与病理差异相关（P＜0.05）。多因素分析结果提示活检块数少（OR=0.574,95%CI：0.363~0.908,P=0.018）是发生活检病理与术后病理差异的独立危险因素。结论 胃黏膜低级别上皮内瘤变及早期胃癌活检病理与术后病理不符的情况临床上较多见,多块活检能提高活检的准确性,降低病理不符情况的发生。