宫颈细胞学阴性且高危型人乳头瘤病毒阳性人群的分流方法

目的 分析宫颈细胞学阴性且高危型人乳头瘤病毒(HPV)阳性患者的宫颈活检病理结果,探讨Cervista HPV HR A9组病毒应用于此类人群分流的可行性。 方法 对1 376例于2011年1月至2016年1月健康查体的女性行新柏氏液基细胞学检测(TCT)和Cervista HPV HR检测,Cervista HPV HR检测结果分为A5/6、A7、A9组,将TCT阴性、HPV阳性患者转诊阴道镜检查,必要时行镜下宫颈活检术,分析A9组病毒感染与宫颈高级别上皮内瘤变CINII⁺(CINII及CINIII)的关系。 结果 A5/6组、A7组及A9组阳性者分别占28.41%、21.51%、50.07%。A5/A6组、A7组及A9组中CINII⁺的发生率分别为1.28%、3.38%、15.82%,A9组中CINII⁺的发生率明显高于另外两组,其差异具有统计学意义(P<0.001, P<0.001)。A9组病毒感染者发生CINII⁺的风险是A5/A6组感染者的12.37倍,是A7组感染者的4.68倍。 结论 Cervista HPV HR A9组病毒可用于TCT阴性、高危型HPV阳性者的分流。     

液基细胞学配合阴道镜检查诊断宫颈病变

目的探讨液基薄层细胞学（TCT）配合阴道镜检查对子宫颈病变的诊断价值。方法TCT配合阴道镜检查对子宫颈病变进行筛查,以组织学诊断为金标准,对结果进行分析。结果TCT检查2238例,采用TBS分类,共检出阳性涂片201例,占8．98％。其中不典型鳞状上皮细胞（ASC）99例（4．42％）;不典型腺细胞（AGC）4例（0．18％）;低度鳞状上皮内病变（LSIL）63例（2．82％）;高度鳞状上皮内病变（HSIL）28例（1．25％）;鳞状细胞癌（SCC）6例（0．27％）;腺癌（AC）1例（0．045％）。对细胞学阳性（包括ASC及以上病变）或细胞学虽阴性但临床高度可疑者共298例行阴道镜检查,其中251例行镜下活组织病理检查。细胞学与阴道镜下活组织病理诊断符合率分别为LSIL 72．41％（63／87）,HSIL 90．32％（CIN2为15／17,CIN3为13／14）,SCC 100％（6／6）,HPV感染符合率71．11％（32／45）。结论采用TCT筛查,可提高宫颈病变的阳性诊断率;细胞学阳性或临床可疑患者应配合阴道镜检查及镜下活检病理诊断,便于进一步明确诊断,及早治疗。     

In utero and neonatal sensitivity of ApcMin/+ mice to radiation-induced intestinal neoplasia

Purpose: To assess the sensitivity of Apc^Min/+ mice (adenomatous polyposis coli Apc, multiple intestinal neoplasia, Min) to the development of intestinal adenomas after x-irradiation in utero, as neonates, or as young adults.

Materials and methods: CHB6 Apc^Min/+ mice were exposed to an acute dose of 2 Gy x-rays either in utero on day 7 or 14 post-conception, as 2-day or 10-day neonates or as 35-day young adults. Tumour identification and counting was performed 200 – 214 days later.

Results: Irradiation as 10-day-old neonates resulted in a significantly greater overall tumour incidence (average of about 130 tumours per animal) than irradiation as 35-day-old young adults (about 70 tumours). Irradiation as 2-day-old neonates resulted in an intermediate incidence (about 85 tumours). In contrast, the greatest tumour incidence observed after in utero irradiation of Apc^Min/+ mice, of about 44 tumours per animal after 2 Gy irradiation at 14 days post-conception, was significantly lower than the incidence in irradiated adults. Tumour incidences after irradiation as 7-day embryos was not significantly raised above numbers in unirradiated controls (about 30 tumours). These tumour numbers include cystic crypts, largely radiation-induced, which were classed as early stage microadenomas on the basis of loss of wild-type Apc⁺ and expression of beta-catenin.

Conclusions: The sensitivity of Apc^Min/+ mice to the induction of intestinal tumours by radiation was shown to be in the order: 10 d neonates >2 d neonates >35 d young adults >14 d fetus >7 d embryo.     

妊娠期宫颈细胞学与阴道镜检查的特征与处理

妊娠期作为女性的一个特殊生理期,宫颈细胞学及阴道镜的表现有其特殊性。妊娠期宫颈特殊的生理改变容易导致诊断误差。近年来宫颈癌的发病率呈上升趋势,正确把握妊娠期宫颈细胞学及阴道镜检查的特征及处理,早诊断早治疗,具有十分重要的意义。本文主要从妊娠期宫颈细胞学的特点、阴道镜检查的宫颈特征、妊娠期宫颈病变的诊断及处理几个方面来阐述。     

昆明地区高危HPV病毒载量与宫颈病变和宫颈癌相关性

目的了解昆明地区高危人乳头瘤病毒(human papilloma virus,HPV)载量与宫颈病变和宫颈癌相关性。方法选取昆明地区妇女两万余例,用杂交捕获Ⅱ(second-generation Hybrid Capture,HC-II)方法检测高危型HPV-DNA,选取3608例进行阴道镜下多点活组织检查送病理检查,宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)患者以宫颈锥切术后病理检查结果为准,宫颈癌患者以术后病理检查为准,分析HPV病毒载量与宫颈病变级别的相关性。结果宫颈炎2420例(67.07%),CINⅠ448例(12.42%)、CINⅡ376例(10.42%)、CINⅢ280例(7.76%)、宫颈癌84例(2.33%)。经秩和检验,5组间的HPV病毒载量比较,差异有统计学意义(H=185.597,P<0.05);CINⅠ与宫颈炎、宫颈癌和CINⅡ的病毒载量比较,差异均无统计学意义(P>0.05);余下各组两两比较差异有统计学意义(P<0.05)。年龄和HPV病毒载量均是宫颈病变和宫颈癌的危险因素。CINⅡ以上病变随着病毒载量的升高,阳性率逐渐增高。而宫颈癌主要集中在中度级别病毒载量之间发病。结论不同宫颈病变级别间HPV病毒载量有差别,HPV病毒载量可作为诊断CINⅡ以上病变的指标。     

不同的子宫颈锥切术后对妊娠及分娩结局的影响

目的探讨不同的宫颈锥切术后对妊娠及分娩结局的影响。方法 2007年5月-2010年5月对144例有生育要求的宫颈上皮内瘤变患者,采用了高频电刀（LEEP）及冷刀锥切手术治疗后,观察两组术后妊娠及妊娠结局、分娩方式并进行对比分析。结果两组妊娠率分别94.85%、84.73%。两组间的流产率及分娩方式差异无统计学意义。观察组早产、胎膜早破、羊膜腔感染综合征、低出生体质量儿、剖宫产率、宫颈裂伤、产后出血的发生率与对照组比较,差异无统计学意义（P〉0.05）。结论不同的宫颈锥切术对患者的生育能力、妊娠结局没有明显影响;但不同的宫颈锥切术的手术方式、深度和手术到妊娠的时间是影响不良妊娠结局的重要因素。     

Early expression of the fractalkine receptor CX3CR1 in pancreatic carcinogenesis

Background:

In pancreatic ductal adenocarcinoma (PDAC), fractalkine receptor CX3CR1 contributes to perineural invasion (PNI). We investigated whether CX3CR1 expression occurs early in PDAC and correlates with tumour features other than PNI.

Methods:

We studied CX3CR1 and CX3CL1 expression by immunohistochemistry in 104 human PDAC and coexisting Pancreatic Intraepithelial Neoplasia (PanIN), and in PdxCre/LSL-Kras^G12D mouse model of PDAC. CX3CR1 expression in vitro was studied by a spheroid model, and in vivo by syngenic mouse graft of tumour cells.

Results:

In total, 56 (53.9%) PDAC expressed CX3CR1, 70 (67.3%) CX3CL1, and 45 (43.3%) both. CX3CR1 expression was independently associated with tumour glandular differentiation (P=0.005) and PNI (P=0.01). Pancreatic Intraepithelial Neoplasias were more frequently CX3CR1+ (80.3%, P<0.001) and CX3CL1+ (86.8%, P=0.002) than matched cancers. The survival of PDAC patients was better in those with CX3CR1+ tumour (P=0.05). Mouse PanINs were also CX3CR1⁺ and -CL1⁺. In vitro, cytokines significantly increased CX3CL1 but not CX3CR1 expression. Differently, CX3CR1 was upregulated in tumour spheroids, and in vivo only in well-differentiated tumours.

Conclusion:

Tumour differentiation, rather than inflammatory signalling, modulates CX3CR1 expression in PanINs and PDAC. CX3CR1 expression pattern suggests its early involvement in PDAC progression, outlining a potential target for interfering with the PanIN transition to invasive cancer.     

Cancer médullaire de la thyroïde (CMT) de l'enfant

Medullary thyroid carcinoma (MTC) is rare in children. MTC is almost always inherited and occurs as part of a multiple endocrine neoplasia type 2A and B, due to germline mutation in the RET proto-oncogene. MTC in the pediatric population is most often diagnosed in the course of a familial genetic investigation. But when the child is the proband, a de novo mutation is most often founded. The main aim is to treat MTC before extrathyroidal extension occurs because when distant metastases are present, it is rarely curable. Treatment is based on total thyroidectomy with cervical lymph node dissection.     

Classic lobular carcinoma in situ and atypical lobular hyperplasia at percutaneous breast core biopsy

BACKGROUND:

No consensus exists on the need to excise breast lesions that yield classic lobular carcinoma in situ (LCIS) or atypical lobular hyperplasia (ALH) (known together as classic lobular neoplasia [LN]) as the highest risk lesion at percutaneous core‐needle biopsy (CNB). Here, the authors report findings from 72 consecutive lesions with LN at CNB and prospective surgical excision (EXB).

METHODS:

Lesions that yielded LN at CNB at the authors' center have been referred for EXB since June 2004, regardless of imaging‐histologic concordance. A lesion was “concordant” if histologic findings provided sufficient explanation for imaging. An upgrade consisted of ductal carcinoma in situ and/or invasive carcinoma at EXB. Statistical analysis, including 95% confidence intervals (CIs), was performed.

RESULTS:

Between June 2004 and May 2009, CNB of 85 consecutive lesions yielded LN without other high‐risk histologies. Eighty of 85 lesions (94%) underwent prospective EXB. Seventy‐two of 85 lesions (90%; 42 LCIS, 30 ALH) had concordant imaging‐histologic findings. EXB yielded low‐grade carcinoma in 2 of 72 cases (3%; 95% CI, 0%‐9%). In both patients, stereotactic, 11‐gauge, vacuum‐assisted biopsy of calcifications yielded calcifications in benign parenchyma and ALH. CNB results were discordant in 8 of 80 lesions (10%; 4 LCIS, 4 ALH), and EXB yielded cancer in 3 of those 8 lesions (38%; 95% CI, 9%‐76%). The upgrade rate was significantly higher for discordant lesions versus concordant lesions (38% vs 3%; P < .01).

CONCLUSIONS:

Prospective excision of LN identified carcinoma in 3% (95% CI, 0%‐9%) of concordant cases versus 38% (95% CI, 9%‐76%) of discordant cases. The current data provide an unbiased assessment of the upgrade rate of LN diagnosed at CNB. Cancer 2013. © 2012 American Cancer Society.     

CADM1 and MAL promoter methylation levels in hrHPV‐positive cervical scrapes increase proportional to degree and duration of underlying cervical disease

Combined detection of cell adhesion molecule 1 (CADM1) and T‐lymphocyte maturation‐associated protein (MAL) promoter methylation in cervical scrapes is a promising triage strategy for high‐risk human papillomavirus (hrHPV)‐positive women. Here, CADM1 and MAL DNA methylation levels were analysed in cervical scrapes of hrHPV‐positive women with no underlying high‐grade disease, high‐grade cervical intraepithelial neoplasia (CIN) and cervical cancer. CADM1 and MAL methylation levels in scrapes were first related to CIN‐grade of the corresponding biopsy and second to CIN‐grade stratified by the presence of ‘normal’ or ‘abnormal’ cytology as present in the accompanying scrape preceding the cervical biopsy. The scrapes included 167 women with ≤CIN1, 54 with CIN2/3 and 44 with carcinoma. In a separate series of hrHPV‐positive scrapes of women with CIN2/3 (n = 48), methylation levels were related to duration of preceding hrHPV infection (PHI; <5 and ≥5 years). Methylation levels were determined by quantitative methylation‐specific PCR and normal cytology scrapes of hrHPV‐positive women with histologically ≤CIN1 served as reference. CADM1 and MAL methylation levels increased proportional to severity of the underlying lesion, showing an increase of 5.3‐ and 6.2‐fold in CIN2/3, respectively, and 143.5‐ and 454.9‐fold in carcinomas, respectively, compared to the reference. Methylation levels were also elevated in CIN2/3 with a longer duration of PHI (i.e. 11.5‐ and 13.6‐fold, respectively). Moreover, per histological category, methylation levels were higher in accompanying scrapes with abnormal cytology than in scrapes with normal cytology. Concluding, CADM1 and MAL promoter methylation levels in hrHPV‐positive cervical scrapes are related to the degree and duration of underlying cervical disease and markedly increased in cervical cancer.