肺癌早期诊断的临床应用研究进展

肺癌发病率和死亡率逐年升高 ,5年生存率 <15 % 〔1〕。在癌前病变、原位癌或微小浸润癌时有多种有效的治疗方法 ,90 %以上的患者可以彻底治愈。因此 ,肺癌 5年生存率低原因主要由于肺癌早期发现、早期诊断和对转移的成功治疗方法的缺乏。所以 ,探讨肺癌早期诊断新方法 ,对于有效控制肺癌十分重要。近几年来 ,随着分子生物学、病理学、影像学及内窥镜技术的发展 ,在肺癌的早期诊断方面取得了一些进展。1　病理学肺鳞癌起源于支气管粘膜上皮的基底细胞、粘液细胞 ,一般经鳞状上皮化生、非典型增生和原位癌 ,演进为浸润癌 ;肺腺癌来源于支气管…     

支气管粘膜上皮不典型增生细胞的形态变化及意义

目的　探讨肺癌早期诊断及随访监测的定量指标。方法　应用HE染色、图像分析技术 ,对正常支气管上皮、鳞化上皮、不典型增生上皮及鳞癌Ⅰ级共 86例支气管粘膜活检组织石蜡切片进行细胞形态定量分析。结果　核面积、核面积差异度、核周长、核周长差异度、核形状因子、核形状因子差异度、核体密度、核浆比值、细胞周长、细胞周长差异度 10项参数随病变阶段的递进呈增加或减少趋势 ;核参数的变化方向反映了癌前病变的发展趋势。结论　支气管粘膜中、重度不典型增生是粘膜从良性向恶性转变的关键阶段 ,细胞形态定量分析对肺鳞癌癌前病变的诊断、监测具有积极意义     

肺癌前病变支气管粘膜上皮不典型增生细胞核DNA含量的变化

目的探讨肺癌早期诊断及随访监测的定量指标。方法应用Ｆｅｕｌｇｅｎ染色、图像分析技术,测定正常支气管上皮、鳞化上皮、不典型增生上皮及鳞癌Ⅰ级者共８４例支气管粘膜活检组织石蜡切片的细胞核ＤＮＡ含量。结果在支气管粘膜由鳞化、不同程度不典型增生到癌的递进中,核ＤＮＡＩＯＤ（积分光密度）均值逐渐增大,４Ｃ（４倍体）细胞比例减少,出现较多的高倍体细胞,重度不典型增生组与鳞癌组的ＤＮＡ含量倍体分布已难相区别。结论４Ｃ及高倍体细胞的数量可作为不典型增生及高危癌前病变的量化标准,对肺鳞癌癌前病变的诊断、监测具有一定意义。     

肺癌前病变研究现状

肺癌的发病率及病死率已跃居各类恶性肿瘤的前列[1,2 ],阐明肺癌的发病机制 ,对肺癌的防治及降低其危害具有十分重要的意义。有研究证明 ,肺癌在形成前 ,经历了一系列癌前期病变过程 ,现就肺癌前病变的研究现状综述如下 ,以便为肺癌前病变的深入研究提供参考。一、肺癌前病变的存在将人胎儿肺短期暴露于致癌因子 ,能诱导肺癌前病变的发生 ,并可获得一个理想的人肺癌发生的模型[3 ]。用 3 甲基胆蒽注入Wistar鼠支气管 ,3 0天后 ,可以观察到支气管上皮出现异型增生 ,腺瘤样增生或腺瘤 ,以及鳞状细胞癌 ;3 0天时支气管上皮异型增生发生率较高…     

自发荧光支气管镜在肺癌诊断中的应用:从研究工具到常规手段

对于支气管内早期肺癌和癌前病变的诊断,自发荧光支气管镜要比传统白光镜更加敏感.自发荧光支气管镜的适应证包括检出高危患者的癌前病变和早期肺癌;用于早期肺癌患者的手术范围选择;用于非小细胞肺癌根治术后的随访监测;还可用于镜下可见肿瘤范围的评估.本文综述自发荧光支气管镜的工作原理、研究现状和未来展望.     

自荧光气管镜在支气管肺癌诊断中的临床应用

[目的]探讨自荧光气管镜(AFB)在支气管肺癌早期诊断中的价值.[方法]对198例临床怀疑支气管肺癌患者采用AFB联合白光气管镜(WLB)检查的诊断结果进行回顾性分析,将病理诊断为恶性肿瘤和不典型增生定义为阳性,正常黏膜、增生、慢性炎症定义为阴性,统计AFB与WLB镜下异常表现及病理结果,比较其对早期肺癌诊断的敏感度.[结果]198例中AFB表现异常者186例,WLB表现异常者133例,160例病理阳性结果中癌变黏膜156例,重度不典型增生4例.AFB发现异常病理证实癌变者156例,假阳性30例,敏感性97.5％,假阳性率16.1％,WLB发现异常病理证实者128例,假阳性5例,敏感性80.0％,假阳性率3.7％,两者在敏感性和假阳性率的差异均有统计学意义(P＜0.05).[结论]对于支气管内癌前病变和早期肺癌的定位诊断,AFB检查比WIB更加敏感.     

胃上皮异型增生的新概念

关于异型增生的诊断标准,在东西方国家的胃肠病学术界存在着很大差异,曾一度导致诊断上的混乱.鉴于此.国际上制定了帕达瓦和维也纳新分类系统,对异型增生的诊断标准提出全新的概念,明确将高级别胃上皮异型增生作为胃癌最早期的镜下可见阶段,只是尚未发生浸润.因此,异型增生作为胃癌前病变这一描述已不再准确.深化对胃上皮异型增生的认识与理解,加强对其形成机制、可逆性和治疗方面的研究,是当前重要的研究课题.     

弥漫型细支气管肺泡癌22例诊断分析

弥漫型细支气管肺泡癌２２例诊断分析重庆医科大学附属第一医院（４０００１６）徐玲罗永艾细支气管肺泡癌（简称肺泡癌），是起源于细支气管及肺泡上皮的一类肺癌，有孤立型和弥漫型两种，现将其归类于腺癌，约占肺癌总数的１％～９％。弥漫型肺泡癌因其临床表现、Ｘ线影...     

食管早癌的内镜诊断

食管癌的死亡率较高,其预后与早期发现、早期诊断密切相关.通常将食管鳞状上皮重度异型增生和原位癌定义为癌前病变,无淋巴结转移的黏膜内癌和黏膜下癌（即T1 N0M0期）定义为早期食管癌.根据食管、胃肠上皮性肿瘤Vienna分类,将原位癌和重度异型增生归类于高级别黏膜内瘤变,轻度和中度异型增生归类于低级别黏膜内瘤变.     

内镜窄带成像技术在早期食管癌及癌前病变诊断中的应用

目的 探讨内镜窄带成像技术(NBI)在食管癌及癌前病变诊断中的价值.方法 对205例患者采用普通胃镜及胃镜NBI检查食管,病灶取病理活检,食管癌及中重度异型增生者进入本研究,比较普通胃镜及胃镜NBI对食管癌及中重度异型增生的诊断价值,分析食管癌及癌前病变的NBI表现.结果 普通放大胃镜不易观察到食管上皮内血管,NBI观察食管黏膜呈淡青色,放大观察可清楚地观察到茶色的食管上皮内血管及青色的深层血管.NBI观察早期食管癌及异型增生病灶呈茶色,病灶处深层血管不能显示.5例中重度异型增生及2例m1癌病灶的上皮乳头内血管环(IPCL)均表现为IPCL-Type Ⅳ-1型改变,2例m2癌为IPCL-Type Ⅳ-2型改变;3例m3及1例sm1癌为IPCL-Type Ⅳ-3型改变;3例sm2及8例进展期癌为IPCL-Type Ⅳ-4型改变.结论 NBI可观察食管黏膜及黏膜下的血管改变,较普通胃镜更易发现早期食管癌及癌前病变病灶.     

Carbonic anhydrase IX antigen differentiates between preneoplastic malignant lesions in non-small cell lung carcinoma.

The MaTu interval (MN)/carbonic anhydrase (CA) IX tumour-associated antigen is a protein that is normally expressed in the gut and belongs to the carbonic anhydrase enzyme family (CA IX). It has been detected in tumour cell lines and in some solid tumours including cervical, oesophageal and clear cell renal carcinoma. This study determined MN/CA IX expression in 65 primary non-small cell lung cancer resected with curative intent and in 38 bronchial preneoplastic lesions, carcinoma in situ or microinvasive carcinoma as well as in normal bronchial tissue. The presence of MN/CA IX was detected using immunohistochemistry and Western blot analysis, whenever frozen material was available. Immunostaining was positive in 52/65 (80%) of the tumour samples. The staining was more often focal than diffuse. The percentage of stained cells in positive tumours was highly variable, ranging 1-85%. The pattern of immunostaining was predominantly cytoplasmic with a membranous reinforcement (87%). The intensity was mainly strong (69%). The presence of the protein in the tumour was confirmed by Western blot analysis in the eight samples tested. All the morphologically normal epithelia, except in close vicinity of tumours in some cases, as well as the preneoplastic bronchial lesions (basal cell hyperplasia, metaplasia and dysplasia) were immunonegative for MN/CA IX expression. In contrast, carcinoma in situ and microinvasive epithelioma showed the presence of MN-immunopositive tumoural cells in 5/7 and 4/5 of the samples, respectively. These data suggest that MN/CA IX is a useful marker for the differentiation between preneoplastic lesions and bronchial non-small cell lung cancer in the lung.     

Lung cancer chemoprevention

Lung cancer is the leading cause of cancer death in the United States, and the majority of diagnoses are made in former smokers. Although avoidance of tobacco abuse and smoking cessation clearly will have the greatest impact on lung cancer development, effective chemoprevention could prove to be more effective than treatment of established, advanced-stage disease. Chemoprevention is the use of dietary or pharmaceutical agents to reverse or block the carcinogenic process and has been successfully applied to common malignancies other than lung (including recent reports on the prevention of breast cancer in high-risk individuals). Despite previous studies in lung cancer chemoprevention failing to identify effective agents, our ability to define the highest-risk populations and the understanding of lung tumor and premalignant biology continue to make advances. Squamous cell carcinogenesis in the bronchial epithelium starts with normal epithelium and progresses through hyperplasia, metaplasia, dysplasia, and carcinoma in situ to invasive cancer. Precursor lesions also have been identified for adenocarcinoma, and these premalignant lesions are targeted by chemopreventive agents in current and future trials. Chemopreventive agents can currently only be recommended as part of well-designed clinical trials, and multiple trials have recently been completed or are enrolling subjects.     

肺癌化学药物预防的研究进展

肺癌是世界范围内癌症致死的首要原因。近年来,针对肺癌的传统治疗手段虽不断发展和改善,但肺癌的病死率未明显改变。除了大力倡导戒烟,化学药物预防有望降低肺癌的发生及抑制肺癌的发展,从而成为近年来研究的热点。化学药物预防是应用饮食和／或药物来抑制或逆转肿瘤的形成,目前已成功用于某些恶性肿瘤的临床预防。虽然已有的研究未能找到有效预防肺癌的药物,但鉴于大部分肺癌的发生是支气管上皮经历正常分化、增生、化生、异常增生及癌变的过程,故找寻可以有效抑制或逆转癌前病变或癌前状态的药物就变得愈发重要。     

COX-2 expression during early lung squamous cell carcinoma oncogenesis.

Cyclooxygenase (COX)-2 is implicated in the oncogenesis of many cancers, and COX-2 inhibitors are effective in preventing the development of tumours, such as in colon cancer. Its expression is increased in nonsmall cell lung cancer and is associated with poor prognosis. The present study assessed COX-2 expression in normal bronchial epithelium, as well as in all the putative precursors of squamous cell carcinomas. COX-2 expression was studied by immunohistochemistry in 106 biopsies collected during autofluorescence bronchoscopy in consecutive patients at high-risk for lung cancer. All biopsies corresponding to normal epithelium or low-grade lesions (lesions up to moderate dysplasia) did not show increased COX-2 expression. Lesions were positive for COX-2 in eight out of 14 severe dysplasia patients, eight out of 14 in situ carcinomas and five out of eight invasive carcinomas. A strong statistically significant difference in COX-2 expression was found between normal epithelium or low-grade lesions and high-grade lesions (severe dysplasia or worse). The positive and negative predictive values of COX-2 expression for high-grade lesion were 100% and 82.35%, respectively. In conclusion, bronchial precursors of squamous cell carcinoma showed increased cyclooxygenase-2 expression and were segregated into low- versus high-grade with a high positive predictive value. Thus, cyclooxygenase-2 appears as a potential early marker of squamous cell carcinoma.     

Pathology of lung cancer

This article reviews current concepts in pathologic classification of lung cancer based on 1999 World Health Organization (WHO)/International Association for the Study of Lung Cancer (IASLC) classification. Preinvasive lesions including squamous dysplasia/carcinoma in situ, atypical adenomatous hyperplasia and diffuse idiopathic pulmonary neuroendocrine cell hyperplasia are discussed in addition to current concepts of bronchioloalveolar carcinoma and neuroendocrine tumors.     

Epidermal growth factor receptor expression in pre-invasive and early invasive bronchial lesions.

The 1999 World Health Organization/International Association for the Study of Lung Cancer histological classification of preneoplastic bronchial lesions has been shown to be reproducible but little is known about its biological significance. The current study evaluated the correspondence between the morphological changes of the bronchial epithelium and epidermal growth factor receptor (EGF-R) expression. Thirteen normal bronchial epithelia, 19 hyperplasia, 16 metaplasia, 10 mild dysplasia, one moderate dysplasia, 10 severe dysplasia (SD), 14 carcinoma in situ (CIS) and 11 microinvasive tumours were assessed. A global EGF-R score obtained by the sum of the positivity score plus the EGF-R staining intensity score was calculated for each lesion. A global EGF-R score of >5 was reached only in one metaplasia, in six SD, in six CIS and in six microinvasive tumours. There was no difference in EGF-R expression between normal, hyperplastic and metaplastic epithelia versus mild dysplasia or between severe dysplasia versus CIS and microinvasive tumours but there was a statistically significant difference between mild versus severe dysplasia. This study demonstrates that epidermal growth factor receptor expression rate changes with the stage of the bronchial lesion, increasing from normal epithelium to carcinoma in situ and microinvasive tumours with a statistically significant difference between mild versus severe dysplasia.     

Premalignant lesions of hepatocellular carcinoma: pathologic viewpoint

The significance of large cell dysplasia and small cell dysplasia as premalignant lesions has been extensively discussed. At present the majority of researchers consider that the former seems to be a secondary change rather than a premalignant lesion, and the latter is strongly suggested to be a premalignant lesion. In the past decade, however, adenomatous hyperplasia (dysplastic nodules), the nodular lesions seen in the cirrhotic liver, has attracted researchers' interest. The significance of adenomatous hyperplasia as a premalignant lesion has been supported by its frequent occurrence in the vicinity of hepatocellular carcinomas (HCC), the presence of adenomatous hyperplasia containing distinct cancerous foci, frequent malignant transformation seen in follow-up studies, and so forth. For histological diagnosis of adenomatous hyperplasia, a thorough understanding of the pathology of well-differentiated HCC at an early stage is essential. Reports from Europe and the United States on dysplastic nodules often include well differentiated HCC at the early stage, possibly because of the lack of opportunity for Western pathologists to see minute early-stage well differentiated HCC. In addition, Western pathologists usually have no concept of "carcinoma in situ" in which no obvious invasive growth is present, and many cases of gastric cancer in the mucosa are diagnosed as dysplasia in Europe and the United State.     

Thermal heterogeneity constitutes a marker for the detection of malignant gastric lesions in vivo

BACKGROUND: Several studies have attempted to investigate the association of thermal difference between malignant tumors and inflammatory benign lesions. In this work, we evaluated whether thermal heterogeneity of solid tumors in the stomach constitutes a marker for the diagnosis of benign, preneoplastic, and malignant lesions. STUDY: A thermistor probe was used that attached to the distal end of a long and steerable, 3fr-thermography catheter passed through the biopsy channel of the gastroscope and came in touch with the stomach epithelium to measure temperature differences (DeltaT) between normal tissue and various types of lesions. The method was applied in 8 patients with benign hyperplastic gastric lesions, 19 patients with gastritis, 9 patients with peptic ulcer, 7 patients with dysplasia and 11 patients with gastric adenocarcinoma. RESULTS: Progressive changes in DeltaT between hyperplastic gastric lesions, gastritis, ulcer, dysplasia and adenocarcinoma were observed (P < 0.001). Statistical analysis showed that DeltaT greater than 1.7 degrees C, constitutes a crucial point for the diagnosis of malignancy, in stomach lesions, with sensitivity (72%) and specificity (94%). CONCLUSIONS: These findings suggest that the detection of DeltaT, between normal tissue and neoplastic lesions, could be useful in clinical practice for the differential diagnosis of stomach lesions, even in the early stages.     

Expression of Ki-67, p53, and K-ras in chronic pancreatitis and pancreatic ductal adenocarcinoma

AIM: To examine surgical specimens of pancreas with either chronic pancreatitis or pancreatic cancer in order to study whether ductal hyperplasia and dysplasia in pancreas represent precursor lesions for pancreatic cancer. METHODS: We examined expression of Ki-67, CEA, p53, and K-ras, in the surgical specimens of pancreas with adenocarcinomas (n= 11) and chronic pancreatitis (n = 12). Cellular proliferation was assessed by Ki-67 proliferation index using the proliferation marker Ki-67. In specimens with pancreas cancer, we divided pancreas epithelium into normal (n = 7), ductal hyperplasia (n = 3), dysplasia (n = 4), and cancerous lesion (n = 11) after hematoxylin and eosin staining, Ki-67, and CEA immunohistochemical staining. In cases with chronic pancreatitis, the specimen was pathologically examined as in cases with pancreas cancer, and they were also determined as normal (n = 10), ductal hyperplasia (n = 4), or dysplasia (n = 5). p53 and K-ras expression were also studied by immunohistochemical staining. RESULTS: In pancreatic cancer, the Ki-67 index was 3.73±3.58 in normal site, 6.62±4.39 in ductal hyperplasia, 13.47±4.02 in dysplasia and 37.03±10.05 in cancer tissue, respectively. Overall, p53 was positive in normal ducts, ductal hyperplasia, dysplasia, and carcinoma cells in 0 of 14 (0%), 0 of 7(0%), 7 of 9 (78%), and 10 of 11 (91%), respectively, and K-ras was positive in 0 of 8 (0%), 1 of 3 (33%), 4 of 6 (67%), 4 of 5 (80%), respectively. CONCLUSION: Our results favorably support the hypothesis that ductal hyperplasia and dysplasia of the pancreas might be precursor lesions for pancreas cancer. Further evaluation of oncogenes by the molecular study is needed.     

17Beta-estradiol modulates gastroduodenal preneoplastic alterations in rats exposed to the carcinogen N-methyl-N'-nitro-nitrosoguanidine.

Gastric cancers are a significant cause of morbidity worldwide. Epidemiological studies and animal models show that males have higher incidences of gastric cancers compared with females, suggesting that sex hormones may modulate gastric cancer risk. An animal model of the initiation phase of gastric cancer was used to determine the effects of systemic estrogen administration on morphological progression of preneoplastic lesions and to define cell populations at which estrogens may act. Preneoplastic progression in antral and duodenal mucosa was examined in male rats that received the chemical carcinogen, N-methyl-N'-nitro-nitrosoguanidine (MNNG), during treatment with implants containing 17beta-estradiol or oil vehicle. Histopathological changes in antral and duodenal gland morphology, numbers of proliferating cells and apoptotic bodies, and antral gastrin cell numbers and protein storage levels were determined 4 weeks later. With MNNG treatment, duodenal villous heights were significantly decreased, and epithelial cells displayed histological features of hyperplasia and dysplasia. Antral glands showed epithelial hyperplasia and dysplasia, increased mucosal height, and decreased mucin levels. Antral gastrin storage protein levels were decreased by MNNG. Systemic treatment with 17beta-estradiol significantly reversed MNNG-induced alterations in duodenal gland heights while increasing mucin and gastrin levels in antral glands. Cell proliferation and apoptosis rates were not significantly different between groups. The present results indicate that systemic 17beta-estradiol treatment influences antral and duodenal gland differentiation during the initiation phase of chemical gastroduodenal carcinogenesis in male rats. These results explain, in part, a potential pathway through which protective effects of estrogens on chemical carcinogenesis are mediated in the upper gastrointestinal tract.