B(a)P诱导小鼠前胃癌过程中组织病理学变化

目的：探讨B(a)P诱导小鼠前胃癌过程中胃组织形态学的动态改变。方法：小鼠用5mg／ml的B(a)P灌胃，每周两次，共4周。以后每隔4周处死一部分小鼠，对胃组织进行病理组织学观察。结果：从第17周开始小鼠前胃开始出现肉眼可见的肿瘤，前胃组织由局部腺体增生、排列紊乱逐步发展为腺体普遍异常增生，形成早期胃癌，进一步发展出现进展期胃癌。结论：B(a)P诱导的小鼠前胃癌的潜伏期大约3个月左右，前胃组织病理学动态变化过程是萎缩性胃炎、不典型增生、胃癌。     

高危型人类乳头瘤病毒检测对不典型鳞状细胞分流监测的临床价值

目的评价高危型人类乳头瘤病毒（HPV）检测对不典型鳞状上皮细胞（atypical squamous cells of undetermined significance，ASCUS）分流临测的临床价值。方法对654例宫颈细胞学检查结果为ASCUS的患者。进行高危型HPV检测和阴道镜检查，镜下定位活检可疑病灶．以病理学诊断作为金标准。结果654例中，高危型HPV检测呈阳性的病例为411例，阳性率为62.8％。经病理学确诊宫颈上皮内瘤样病变（CIN）病例为58例，占总数的8．9%（58／654），其中CIN Ⅱ和CIN Ⅲ共计43例．占CIN的74．1％（43／58）；CINⅡ，CINⅢ的高危型HPV阳性率分别为80．8％及94．1％。ASCUS患者中以高危型HPV检测、直接选择阴道镜检查，检出CIN的敏感度分别为88.9％和65．5%；对诊断CINⅡ和CINⅢ。高危型HPV的敏感度为94．1％，阴道镜的敏感度为65．1％。结论ASCUS患者中高危型HPV的CINⅡ和CINⅢ检出有较高的敏感度，对ASCUS可有效地进行分流监测，患者可不必再做阴道镜检查和活检。     

宫颈上皮内瘤变阴道镜下活检与电环切除术后病理的对比分析

目的 对比分析宫颈上皮内瘤变（CIN）阴道镜下活检与电环切除术后病理，提高CIN诊断的准确性。方法 回顾性对比分析216例宫颈上皮内瘤变阴道镜下活检与电环切除术后病理，探讨影响两者符合率的相关因素。结果 两者对比，宫颈电环切除术（LEEP）后病理结果与阴道镜下活检相符的74例，升级的18例，降级的124例。阴道镜下检查不满意者活检与电环切除术后病理对比，升级率大于阴道镜下检查满意者，差异有显著性（P〈0．01）。结论 宫颈转化区向宫颈管上移者，要注意宫颈管内的病变。宫颈电环切除术可以部分弥补阴道镜下活检的缺陷，且有治疗作用。     

高危型人乳头瘤病毒DNA检测在宫颈癌筛查中的作用

目的:探讨高危型人乳头瘤病毒(HPV)DNA检测在宫颈癌筛查中的作用。方法:2005年4月~2006年4月在我院妇科门诊就诊2 340名妇女进行宫颈癌前病变筛查,采用第2代杂交捕获试验(HC-Ⅱ)检测高危型HPV DNA联合薄层液基细胞学检查,同时进行阴道镜检查,并以宫颈活检的组织病理学为确诊标准。结果:筛查并经病理诊断为HPV感染365例,宫颈上皮内瘤变(C IN)Ⅰ级71例,C INⅡ48例,C INⅢ55例,宫颈浸润癌31例。以组织病理学为确诊标准,高危型HPV DNA检测C INⅡ、C INⅢ的敏感度是91.33%,特异度是74.51%,阳性预测值是5.21%,阴性预测值是99.79%。宫颈细胞学筛查C INⅡ、C INⅢ,以未明确诊断意义的不典型鳞状上皮细胞(ASCUS)为分界点的敏感度、特异度、阳性预测值、阴性预测值分别是90.80%、80.45%、12.30%、99.50%;以高度鳞状上皮内病变(HSIL)为分界点的敏感度、特异度、阳性预测值、阴性预测值分别是98.90%、73.98%、4.90%、100.00%。高危型HPV DNA在不同宫颈病变中的阳性率分别是:宫颈癌88.57%(31/35),C INⅢ91.67%(66/72),C INⅡ87.50%(56/64),C INⅠ42.00%(21/50)。结论:高危型人乳头瘤病毒DNA检测在宫颈癌前病变的筛查中有很高的敏感度和阴性预测值,高危型HPV DNA联合细胞学检查可使敏感度和阴性预测值有提高,但特异度未能提高。     

自制组织芯片检测宫颈上皮内瘤变中p16蛋白的表达

目的:研究p16蛋白在宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)中的表达及探讨其辅助诊断价值.方法:利用自制组织芯片进行184例CIN病变上皮和30例正常上皮HE光镜观察和免疫组化检测p16蛋白表达.结果:①自制组织芯片切片染色满意,达到较大标本量研究要求;②p16蛋白在10例正常对照和20例病变组织中的正常鳞状上皮与腺上皮均阴性表达,在CIN1中为88.1%(52/59),在CIN 2、CIN 3中均为100.0%表达,且表达的强度与CIN分级明显相关,有显著统计学意义(P＜0.001).CIN 1大部分阳性细胞限于上皮层的下1/3,CIN 2限于上皮的下2/3,而CIN 3则较多超过上皮的2/3或全层弥漫阳性,其表达层次与CIN分级明显相关,有显著统计学意义(P＜0.001).结论:在宫颈CIN的诊断及分级中,p16蛋白作为辅助诊断标记物有较好的应用价值;而自制的组织芯片成本低,质量上能达到科研要求,值得基层单位应用.     

宫颈环形电刀切除术治疗212例宫颈上皮内瘤变价值探讨

目的:探讨宫颈环形电刀切除术(LEEP)治疗宫颈上皮内瘤变(CIN)的价值。方法:回顾分析2000年3月至2004年10月212例CIN患者在阴道镜辅助下行宫颈环形电切术的治疗情况。结果:阴道镜下宫颈异常结构处取活检病理结果为CIN者212例行宫颈环形电切术(LEEP),LEEP术后病理检查:宫颈粘膜慢性炎症13例(6.1%)、CINⅠ90例(42.5%)、CINⅡ77例(36.3%)、CINⅢ24例(11.3%),原位癌累及腺体伴早期浸润癌8例(3.8%)。术后195例(92.0%)宫颈标本边缘病理学检查未见CIN病变;术后降级者70例(33.0%),等级者122例(57.5%),升级者20例(9.4%);治愈率达89.2%。结论:LEEP治疗CIN安全有效、简单易行、并发症少、避免了二次手术和过度治疗,能保留患者的生育能力,在治疗的同时能进行诊断。但术后仍需定期和规范的随访以防止宫颈癌的发生和发展。     

Angiogenesis in cervical intraepithelial neoplasia and early-staged uterine cervical squamous cell carcinoma: clinical significance

The objective of this study is to evaluate angiogenesis in cervical intraepithelial neoplasia (CIN), microinvasive squamous cell carcinoma (MIC), and early-staged squamous cell carcinoma (SCC), stage IB-IIA of the cervix. Microvessel density (MVD) was evaluated and correlated with other pathologic prognostic factors and disease outcomes. Four hundred seventy-four cervical specimens were studied. Among these, 100 were designated normal cervix, 30 CIN1, 32 CIN2, 178 CIN3, 74 MIC, and 60 early-staged SCC. MVD per high-power field (x400) of early-staged SCC, MIC, and CIN3 were significantly higher in comparison to CIN2, CIN1, and control subjects (P<0.05). There was no statistically significant difference in MVD between control group, CIN1, and CIN2. In early-staged SCC, no correlation between MVD and pelvic lymph node status, parametrial involvement, depth of stromal invasion, and lymphovascular space invasion was found. Patients with bad outcomes (recurrence or death) showed no statistically different MVD from the ones who had unremarkable clinical courses.     

Chronic inhalation exposure to mainstream cigarette smoke increases lung and nasal tumor incidence in rats.

An animal model of lung carcinogenicity induced by chronic inhalation of mainstream cigarette smoke would be useful for research on carcinogenic mechanisms, smoke composition-response relationships, co-carcinogenicity, and chemoprevention. A study was conducted to determine if chronic whole-body exposures of rats would significantly increase lung tumor incidence. Male and female F344 rats (n = 81 to 178/gender) were exposed whole-body 6 h/day, 5 days/week for up to 30 months to smoke from 1R3 research cigarettes diluted to 100 (LS) or 250 (HS) mg total particulate matter/m(3), or sham-exposed to clean air (C). Gross respiratory tract lesions and standard lung and nasal sections were evaluated by light microscopy. A slight reduction of survival suggested that the HS level was at the maximum tolerated dose as commonly defined. Cigarette smoke exposure significantly increased the incidences of non-neoplastic and neoplastic proliferative lung lesions in females, while nonsignificant increases were observed in males. The combined incidence of bronchioloalveolar adenomas and carcinomas in females were: HS = 14%; LS = 6%; and C = 0%. These incidences represented minima because only standard lung sections and gross lesions were evaluated. Mutations in codon 12 of the K-ras gene occurred in 4 of 23 (17%) tumors. Three mutations were G to A transitions and one was a G to T transversion. The incidence of neoplasia of the nasal cavity was significantly increased at the HS, but not the LS level in both males and females (HS = 6%, LS = 0.3%, C = 0.4% for combined genders). These results demonstrate that chronic whole-body exposure of rats to cigarette smoke can induce lung cancer.     

Familial hyperparathyroidism syndromes

Primary hyperparathyroidism is a common endocrine disorder and the most prevalent cause of hypercalcemia worldwide. While most cases are sporadic, 5–10% of cases are inherited as part of a familial syndrome: multiple endocrine neoplasia (MEN-1, MEN-2A, MEN-4), hyperparathyroidism jaw-tumor syndrome (HPT-JT), familial hypocalciuric hypercalcemia (FHH), neonatal severe hyperparathyroidism (NSHPT), autosomal dominant moderate hyperparathyroidism (ADMH), or familial isolated hyperparathyroidism (FIHPT). Recent developments in molecular pathology identified specific germline mutations (MEN1, RET, CDKIs, CDC73/HRPT2, CaSR, GNA11, AP2S1) implicated in their pathogenesis. In contrast to sporadic primary hyperparathyroidism which is usually caused by a solitary parathyroid adenoma, hereditary hyperparathyroidism tend to present with multiglandular parathyroid disease, with variable penetrance according to the genetic syndrome. As a result, the clinical severity of each familial condition varies tremendously, resulting in distinct prognosis and treatment strategies. With the advent of molecular testing, genetic subtyping has become an integral part of treatment decision making, requiring correlation with clinical and pathologic findings. This review provides an update on the current knowledge of hereditary hyperparathyroidism and its associated genetic syndromes.     

Pharmacotherapy of Zollinger–Ellison syndrome

Introduction: The role of pharmacotherapy in the management of patients with Zollinger–Ellison syndrome (ZES) is often equated with the medical management of acid hypersecretion. However, pharmacotherapy is also increasingly involved in the other management areas of these patients.

Areas covered: This paper reviews the role of pharmacotherapy in all aspects of the management of patients with ZES. Newer aspects are emphasized. This includes the difficulty of diagnosing ZES in patients taking proton pump inhibitors. Also covered is the role of pharmacotherapy in controlling acid hypersecretion and other hormonal hypersecretory states these patients may develop, including hyperparathyroidism in patients with multiple endocrine neoplasia type 1 and ZES; tumor localization; and the treatment of advanced metastatic disease. The last includes chemotherapy, liver-directed therapies, biotherapy (somatostatin/interferon), peptide radio-receptor therapy and molecular-targeted therapies including the use of mTor inhibitors (everolimus) and tyrosine kinase inhibitors (sunitinib).

Expert opinion: Pharmacotherapy is now involved in all aspects of the management of patients with ZES, with the result that ZES has progressed from being considered an entirely surgical disease initially to the present where medical treatment plays a major role in almost all aspects of the management of these patients.