宫颈病变Ki67和P53表达的定量分析及其临床意义

目的定量探讨Ki67和P53在子宫颈鳞状细胞癌（SCC）、宫颈上皮内瘤变（CIN）及慢性炎症中的表达特点、变化规律及其临床意义。方法用免疫组化和图像定量分析技术检测11例宫颈癌、27例宫颈上皮内瘤变（其中CINⅠ10例,CINⅡ6例,CINⅢ11例）及7例子宫颈慢性炎症（CC—itis）的石蜡标本中Ki67和P53表达的阳性单位。结果Ki67和P53在SCC、CIN及CC—itis组织中表达的阳性单位（PU）差异具有显著性（F=26．447,F=9．564,P均〈0．001）,SCC、CIN病变中Ki67和P53表达的阳性单位明显高于CC．itis,差异具有显著性（P均〈0．001）。CIN病变中Ki67的阳性单位具有随CIN分级增高而增大的趋势（单侧检验P〈0．05）。CINⅢ组中Ki67表达的阳性单位明显高于CINⅠ组,差异有统计学意义（P=0．023）;P53的阳性单位在CIN不同级别的比较中差异具有显著性（P=0．01）,CINⅡ组中P53的阳性单位明显高于CINⅠ组,差异有统计学意义（P=0．003）。宫颈病变需手术组的Ki67和P53的阳性单位均明显高于保守治疗组,差异具有统计学意义（P均〈0．001）。结论Ki67和P53的表达强度与宫颈慢性炎症、宫颈上皮内瘤变及宫颈鳞状细胞癌有关,两者在组织中表达的阳性单位对于区分宫颈炎性病变和上皮内瘤变,区分低级别和高级别上皮内瘤变,包括CINI和CINⅡ的区分,以及对于治疗方案的拟定均具有重要价值;此外Ki67表达的阳性单位有助于CIN分级。     

Dichotomous role of the serine/threonine kinase MAP4K4 in pancreatic ductal adenocarcinoma onset and metastasis through control of AKT and ERK pathways

MAP4K4 is a serine/threonine kinase of the STE20 family involved in the regulation of actin cytoskeleton dynamics and cell motility. It has been proposed as a target of angiogenesis and inhibitors show potential in cardioprotection. MAP4K4 also mediates cell invasion in vitro, is overexpressed in various types of cancer, and is associated with poor patient prognosis. Recently, MAP4K4 has been shown to be overexpressed in pancreatic cancer, but its role in tumour initiation, progression, and metastasis is unknown. Here, using the Kras^G12D Trp53^R172H Pdx1-Cre (KPC) mouse model of pancreatic ductal adenocarcinoma (PDAC), we show that deletion of Map4k4 drives tumour initiation and progression. Moreover, we report that the acceleration of tumour onset is also associated with an overactivation of ERK and AKT, two major downstream effectors of KRAS, in vitro and in vivo. In contrast to the accelerated tumour onset caused by loss of MAP4K4, we observed a reduction in metastatic burden with both the KPC model and in an intraperitoneal transplant assay indicating a major role of MAP4K4 in metastatic seeding. In summary, our study sheds light on the dichotomous role of MAP4K4 in the initiation of PDAC onset, progression, and metastatic dissemination. It also identifies MAP4K4 as a possible druggable target against pancreatic cancer spread, but with the caveat that targeting MAP4K4 might accelerate early tumorigenesis. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.     

金昌队列人群结直肠癌疾病负担分析

目的 评价金昌队列人群结直肠癌的疾病负担及变化趋势。方法 应用历史队列研究方法收集金昌队列人群2001－2013年结直肠癌全死因资料及2001－2010年结直肠癌住院患者病案资料,应用死亡率、标化死亡率、直接住院费用、潜在减寿年(PYLL)、人均PYLL(APYLL)、潜在工作损失年(WPYLL)以及人均WPYLL(AWPYLL)等指标描述结直肠癌造成的疾病负担状况,运用Spearman秩相关和平均增长速度分析疾病负担的变化趋势。结果 2001－2013年金昌队列人群结直肠癌粗死亡率为9.53/10万,平均年增长速度为12.89%。结直肠癌造成该队列人群PYLL、APYLL、WPYLL和AWPYLL分别为485.00人年、9.15年、253.00人年和4.77年。2001－2010年该队列人群结直肠癌住院患者人均例次直接住院费用为7 064.38元,日均直接住院费用为408.43元,均无明显增长趋势。结论 金昌队列人群结直肠癌死亡率呈上升趋势,疾病负担逐渐沉重。     

康复新液与浓替硝唑对低危妊娠滋养细胞肿瘤MTX化疗后口腔溃疡的疗效观察

目的比较康复新液与浓替硝唑含漱液对低危妊娠滋养细胞肿瘤MTX化疗性口腔溃疡的临床疗效。方法我院2013年12月至2015年12月收治的低危滋养细胞肿瘤患者,选取50例合并口腔溃疡患者作为研究对象,分为2组,每组25例。治疗组:给予康复新溶液,对照组给予浓替硝唑含漱液,评价两组疗效和毒副反应。结果康复新液组治疗有效率为96%,浓替硝唑组为80%,两组比较差异有统计学意义(P<0.05)。口腔溃疡的愈合情况比较:治疗组愈合时间为(4.3±1.9)d;对照组为(7.1±2.6)d,两组比较差异有统计学意义(P<0.05)。所有患者均未发生与康复新液和浓替硝唑相关的不良反应。结论康复新液治疗低危妊娠滋养细胞肿瘤患者相关化疗性口腔溃疡安全有效,值得临床推广。     

Reproductive outcomes after hydatiform mole and gestational trophoblastic neoplasia

Abstract

Gestational trophoblastic disease includes complete hydatidiform mole (CHM) or partial hydatidiform mole (PHM) and gestational trophoblastic neoplasia (GTN). Given the very high-curability rate of trophoblastic disease, the risk of further molar pregnancy after CHM or PHM as well as the risk of second primary tumors and fertility compromise after chemotherapy for GTN represent major concerns. The incidence of subsequent molar pregnancy ranges from 0.7 to 2.6% after one CHM or PHM, and is approximately 10% after two previous CHMs. Among patients who have received chemotherapy, there is an increased risk of myeloid leukemia which is mainly related to the cumulative dose of etoposide. Resumption of normal menses occurs in approximately 95% of women treated with chemotherapy, but menopause occurs 3 years earlier compared with those non-treated with chemotherapy. Term live birth rates higher than 70% without increased risk of congenital abnormalities have been reported in these women, and pregnancy outcomes are comparable to those of general population, except a slightly increased risk of stillbirth. Fertility-sparing treatment for placental site trophoblastic tumor is a therapeutic option reserved to highly selected, young women who do not present markedly enlarged uterus or diffuse multifocal disease within the uterus.     

The relationship between previous treatment for cervical dysplasia and preterm delivery in twin gestations

Abstract

Objective: To describe the impact of previous cervical surgery on preterm birth prior to 34 weeks in twins.

Methods: A retrospective review of twin pregnancies delivered between January 1998 and December 2005 at two institutions was performed. Women with a prior cold knife cone (CKC), loop electrosurgical excision procedure (LEEP), or ablative procedure were compared to a control group of women who had not undergone a previous treatment for cervical dysplasia. The primary outcome was delivery before 34 weeks of gestation.

Results: A total of 876 women met inclusion criteria. Of these, 110 (12.6%) had previous surgical procedures for cervical dysplasia, including CKC (n?=?10), LEEP (n?=?36), cryotherapy (n?=?59) and CO₂ laser treatment (n?=?5). Delivery prior to 34 weeks was more common in women with a previous CKC compared to women with no prior treatment (40% versus 11.3%; odds ratio [OR], 3.6; 95% confidence interval [CI], 1.7–8.0). Delivery prior to 34 weeks was not more common in women with a previous LEEP (8.3%; OR, 0.8; 95% CI, 0.3–2.3) or ablative procedure (9.4%; OR, 0.9; 95% CI, 0.4–1.9) in comparison to the untreated group. Adjusting for the potential confounders of age, tobacco use, infertility treatments and previous preterm birth did not change the results.

Conclusions: Previous CKC is associated with delivery prior to 34 weeks while LEEP and ablative procedures are not. CKC should be carefully considered and avoided when possible in reproductive age women.     

The effect of cervical cerclage on pregnancy outcomes in women following conization

Abstract

Objectives: To determine the effect of cervical cerclage on obstetrical complications and perinatal outcomes of patients following conization.

Design: A retrospective population based cohort study.

Setting: Tertiary academic medical center that covers all the deliveries of the region.

Population: All patients with previous cervical conization who delivered between the years 1994–2011.

Methods: A retrospective population based study.

Main outcome measures: The effect of cerclage placement on the rate of preterm birth.

Results: During the study period there were 109 deliveries of patients following a cervical conization. Cervical cerclage was placed in 22 deliveries that served as the study group and the rest (n?=?87) served as the comparison group. The rate of early preterm delivery (PTD; <34 weeks) was significantly higher in women who had a cerclage. In a logistic regression model, cerclage was found to be an independent risk factor for early PTD.

Conclusion: Cerclage is an independent risk factor for early PTD In patients who had a conization due to CIN.     

阴道镜下宫颈活检诊断CIN1中漏诊CIN2及以上病变的分析

目的 评价阴道镜下活检诊断CIN1的准确性,探讨漏诊CIN2及以上病变(简称CIN2+)的因素.方法 对109例阴道镜下活检诊断CIN1的患者施以宫颈环形电切术(LEEP),对照比较术前术后组织病理学诊断的符合率,并回顾性分析术前各因素与漏诊CIN2+的相关性.结果 LEEP前后CIN1的符合率52.29％(57/109),CIN1中CIN2+漏诊率47.71％ (52/109).宫颈细胞学ASC-H/HSIL、阴道镜检查Ⅲ型转化区、年龄＞40岁、HR-HPV DNA负荷量≥100 pg/ml均为漏诊CIN2+的独立高危因素(相对危险度分别为5.24、5.08、3.16、3.13).结论 阴道镜下活检诊断CIN1存在CIN2+的漏诊.先前细胞学的严重程度是目前诊治规范中选择随访或干预的依据,但转化区类型、年龄、病毒负荷量等也是个体化处理中需考虑的问题.