Wait-and-see policy versus loop excision after two consecutive Pap-2 cervical smears: over time less surgery and an equivalent outcome; no substantial contribution to be expected from the detection of high risk human papillomavirus

OBJECTIVE: To determine the number interventions and outcomes in patients referred with two consecutive Pap 2 cervical smear results who were managed either by a wait-and-see policy or aggressively, and to determine whether triage with high-risk human papillomavirus (hr-HPV) detection, resulting in the referral of only hr-HPV positive patients, would lead to the detection of all patients with cervical intraepithelial neoplasia (CIN). DESIGN: Retrospective comparison and retrospective cohort study. METHOD: 282 patients referred in 1997/'99 with 2 consecutive Pap 2 cervical smears in the screening program were included. Patients referred to the UMC St Radboud Hospital (n = 140; mean age: 45 years) underwent a colposcopy during which only lesions suggestive for CIN 3 were treated. All other colposcopic lesions (CIN 2 or less) were not treated but followed prospectively. Patients referred to the Canisius Wilhelmina Hospital (CWZ) (n = 142; mean age: 44 years) underwent colposcopy during which all colposcopic lesions (including CIN 2 or less) were treated directly. The two groups were compared in terms of the final cytological follow-up, the number of loop excisions, and the number of patients with CIN. The mean follow up was 40 months. In the first group, the effect of triage using hr-HPV detection was also investigated retrospectively. RESULTS: With the wait-and-see approach, statistically significantly fewer diathermic loop excisions were done: 13 versus 124. After the follow-up period there was no statistically significant difference between the two groups in terms of the number of patients with persisting Pap 2: 16 (11%) versus 12 (8%). Triage with hr-HPV detection would identify all patients with CIN 3, 50% of the patients with CIN 2, and none of the patients with CIN 1; of the 48 hr-HPV-positive women, 1 had a CIN 3 lesion and 3 had a CIN 2 lesion; of the remaining 92 women, 2 had a CIN 1 lesion and 3 had a CIN 2 lesion. CONCLUSION: The wait-and-see approach led to fewer interventions, while the number of women with persisting Pap 2 smears was not higher than with the aggressive approach. Triage with hr-HPV may reduce the number of referrals and colposcopies, but follow-up remains necessary in all women regardless of hr-HPV status.     

Coexisting high-grade glandular and squamous cervical lesions and human papillomavirus infections

The frequency of high-risk human papillomavirus (hr-HPV) genotypes in patients with adenocarcinoma in situ (ACIS) with coexisting cervical intraepithelial neoplasia (CIN), ACIS without coexisting CIN, and high-grade CIN (CIN II/III) was studied, in order to gain more insight into the relation between hr-HPV infections and the development of coexisting squamous and glandular lesions. The SPF(10) LiPA PCR was used to detect simultaneously 25 different HPV genotypes in biopsies obtained from 90 patients with CIN II/III, 47 patients with ACIS without coexisting CIN, and 49 patients with ACIS and coexisting CIN. hr-HPV was detected in 84 patients (93%) with CIN II/III, 38 patients (81%) with ACIS without CIN, and in 47 patients (96%) with ACIS and coexisting CIN. A total of 13 different hr-HPV genotypes were detected in patients with CIN II/III, and only five in patients with ACIS with/without coexisting CIN. HPV 31, multiple hr-HPV genotypes, and HPV genotypes other than 16, 18, and 45 were significantly more often detected in patients with CIN II/III, while HPV 18 was significantly more often detected in patients with ACIS with/without CIN. There were no significant differences in the frequency of specific hr-HPV genotypes between patients with ACIS with or without coexisting CIN. In conclusion, the frequency of specific hr-HPV genotypes is similar for patients with ACIS without CIN and patients with ACIS and coexisting CIN, but is significantly different for patients with CIN II/III without ACIS. These findings suggest that squamous lesions, coexisting with high-grade glandular lesions, are aetiologically different from squamous lesions without coexisting glandular lesions.     

MR imaging of facial nerve enhancement in Bell palsy or after temporal bone surgery

The authors evaluated magnetic resonance (MR) images obtained with intravenously administered gadolinium in ten patients who had facial paralysis and no facial nerve tumor. In patients with either Bell palsy (four patients) or facial paralysis after temporal bone surgery (six patients), intratemporal facial nerve enhancement was seen. Facial nerve enhancement on MR images proved to be a nonspecific finding.     

骨关节炎大鼠关节软骨修复与橄榄叶提取物的干预效应

目的:观察橄榄叶提取物对白陶土及鹿角菜胶诱导的大鼠骨关节炎组织炎症的预防作用及对关节软骨的修复作用。方法:试验于2005-11/12在大连医科大学中日合作医药科学研究所进行。实验动物:选择健康雄性SD大鼠80只。实验材料:受试物橄榄叶提取物[由日本国Eisai食品与化学有限公司(日本国东京市)提供]。实验分组及给药:按体质量将大鼠随机分为5组,每组16只。模型对照组,灌胃给予蒸馏水,消炎痛组,灌胃给予消炎痛2mg/kg体质量,其余3组为橄榄叶提取物组,分别给予橄榄叶提取物(活性成分为以羟基酪醇为主的多酚)25,50,100mg/kg体质量灌胃,连续5d。第1天给药后1h,采用白陶土与鹿角菜胶诱发大鼠单发亚急性关节炎。实验评估:①诱发关节炎后1,3,5d,用容积测量法测定每组8只大鼠的左右后肢足跖体积,计算肿胀度,并同时用游标卡尺测定其胫跗骨关节最大径。②诱发关节炎后第5天,测定大鼠足跖伊文思蓝含量。每组的另8只大鼠,在诱发关节炎第5天麻醉后处死,剪下右足跖做组织病理学检查,观察橄榄叶提取物对大鼠骨关节炎中组织炎症的预防作用及对关节软骨的修复作用。结果:80只大鼠全部进入结果分析。①足跖肿胀度及胫跗骨关节径:诱发关节炎后1,3,5d,橄榄叶提取物50mg/kg组和100mg/kg组大鼠的右后足跖肿胀度均明显小于模型对照组大鼠[1d:(46.7±4.2)%,(44.8±6.8)%,(52.5±4.0)%;3d:(40.4±4.8)%,(37.4±5.7)%,(45.0±2.9)%;5d:(34.5±4.8),(31.7±5.3)%,(40.4±4.0)%,P<0.05],橄榄叶提取物25mg/kg体质量组,50mg/kg体质量组,100mg/kg体质量组大鼠的右后胫跗骨关节径与模型对照组大鼠比较差异无显著性(P>0.05)。②足跖伊文思蓝含量:诱发关节炎后第5天,橄榄叶提取物50mg/kg,100mg/kg组大鼠的右后足跖伊文思蓝含量均明显小于模型对照组大鼠(P<0.05)。③组织病理学检查及评分:组织病理学检查可见,与模型对照组比较,橄榄叶提取物50mg/kg组,100mg/kg组大鼠骨关节炎中组织炎症浸润明显减少,软骨组织无破坏,且组织病理学评分也明显小于模型对照组(P<0.05)。结论:橄榄叶提取物在50mg/kg体质量及以上剂量能有效地预防白陶土与鹿角菜胶诱发的大鼠骨关节炎中组织炎症,且对软骨有修复作用。     

Cytokine analysis as a tool to understand tumour-host interaction in ovarian cancer

Epithelial ovarian cancer (EOC) is an immunogenic tumour and exploits many suppressive ways to escape immune eradication. EOC is known to spread primarily by tumour cell implantations in peritoneal cavity. Therefore, ascites may be an ideal fluid compartment to unravel the immune status of the peritoneal cavity.We analysed the expression of IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IFN-γ, TNF-α, TNF-β, TGF-β and CCL22 in ovarian cancer ascites, representing immune activating and suppressing cytokines.We observed high expression of pro-inflammatory cytokines IL-6, IL-8 and immune suppressive cytokines IL-10, CCL22 and TGF-β in most samples whereas Th1 (IL-12p70, IFN-γ) and Th2 (IL-4, IL-5) cytokines were only detectable in 13% of the samples. TGF-β was only detected in latent form, questioning its immune suppressive role. CCL22 was in similar levels present in early stage compared to advanced stage tumours. At advanced stage, we observed a negative correlation with CCL22 levels and Th1/2 cytokine expression. We found a positive correlation between IL-6 concentration in ascites and residual disease after debulking. Additionally, IL-6 levels were remarkably higher at recurrence compared to primary advanced disease, which opens an opportunity for inhibition of IL-6 expression in the prevention of recurrence. Despite the heterogeneity of EOC and the complexity of cytokine functions, our results show that cytokine analysis in ascites may aid in understanding tumour-host interaction in EOC.     

Decreased intraperitoneal disease recurrence in epithelial ovarian cancer patients receiving intraperitoneal consolidation treatment with yttrium-90-labeled murine HMFG1 without improvement in overall survival

This study analyzes the site of disease recurrence in ovarian cancer patients to assess the influence of a single intraperitoneal (IP) administration of yttrium-90-labeled murine monoclonal antibody HMFG1 ((90)Y-muHMFG1) on the pattern of disease recurrence. In a large phase III trial ovarian cancer patients in complete clinical remission with FIGO stage Ic-IV were randomized between standard treatment plus a single IP (90)Y-labeled muHMFG1 versus standard treatment alone after negative second-look laparoscopy. Case report forms of all patients with disease recurrence were reviewed to determine site and date of recurrent disease. In total 447 patients were included in the study with a median follow-up of 3.5 years. Relapse was seen in 104/224 in the active and 98/223 in the control arm. Significantly fewer IP (p < 0.05) and more extraperitoneal (p < 0.05) relapses occurred in the active treatment arm. Time to IP recurrence was significantly longer (p = 0.0019) and time to extraperitoneal recurrence was significantly shorter for the active treatment arm (p < 0.001). The impact of IP radioimmunotherapy on IP relapse-free survival could only be seen in the subgroup of patients with residual disease after primary surgery (HR, 0.31; 95% CI, 0.18 to 0.53; p = 0.002). Although, there is no survival benefit for IP radioimmunotherapy as consolidation treatment for epithelial ovarian cancer, we found an improved control of IP disease, that was offset by increased extraperitoneal recurrences.