Gene deletions in an infertile man with sperm fibrous sheath dysplasia

BACKGROUND: Asthenozoospermia may sometimes be related to geneticstructural defects of the sperm tail detectable by transmissionelectron microscopy. Dysplasia of the fibrous sheath (DFS) isa genetic sperm defect, characterized by dysplastic developmentof the axonemal and periaxonemal cytoskeleton. We report thecase of an infertile man with normal sperm count and total spermimmotility in which dysplasia of the fibrous sheath, Akap3,Akap4 gene deletions, meiotic segregation of chromosomes 18,X and Y and Y microdeletions were investigated. METHODS: A 32-year-oldman with a 3-year history of primary infertility presented atour Regional Referral Center for Male Infertility. Family medicalhistory, lymphocyte karyotype, PCR analysis, physical examination,hormone assays and semen analysis were performed. RESULTS: Ultrastructuralsperm evaluation showed dysplasia of the fibrous sheath. Immunostainingof AKAP4 protein was negative in sperm tails. PCR analysis revealedintragenic deletions of the Akap3 and Akap4 genes. Fluorescencein situ hybridization on sperm showed a high frequency of XYdisomy. CONCLUSION: In this infertile patient, our results suggesta possible relationship between dysplasia of the fibrous sheath,partial deletions in the Akap3 and Akap4 genes and absence ofAKAP4 protein in the fibrous sheath. These findings, however,were not detected in another four patients with dysplasia ofthe fibrous sheath. Our results require future confirmatorymolecular analyses.     

解毒破瘀法抑制三阴性乳腺癌复发与转移的临床研究

目的?观察解毒破瘀法抑制三阴性乳腺癌（TNBC）复发与转移的临床疗效。方法?40例三阴性乳腺癌术后患者随机分为治疗组和对照组,各20例,对照组根据辨证施治随证加减,治疗者在辨证施治的同时加用解毒破瘀法,治疗3年,观察3年无病生存率(DFS)。结果?治疗组20例患者3年DFS为100%,对照组为75%,P<0.05。结论?解毒破瘀法能有效抑制三阴性乳腺癌复发及转移。      

Is OSNA better than imprint cytology for intraoperative diagnosis of cancer involvement of axillary sentinel node in breast cancer?

ObjectiveThe study aim was to establish Sensitivity, Specificity, Positive Predictive Value, Negative Predictive Value (NPV), and Accuracy Values of both imprint cytology (IC) and the OSNA assay for intraoperative assessment of axillary sentinel node (SN) cancer involvement in breast cancer. Specifically, we wished to find out if true positive and false negative results of IC were associated to axillary lymphadenectomy (ALND). Also, we addressed a comparative cost analysis between techniques.Methods244 patients treated for breast cancer in the Breast Unit of Hospital Germans Trias i Pujol from 2011 to 2015 were prospectively included. A transversal, consecutive design was applied to assess IC compared to the reference test (OSNA). Inclusion criteria were: T1 and T2 tumors with negative nodes, both clinically and on ultrasound.ResultsSensitivity of IC for macrometastases was 70%. The NPV of IC for macrometastases was 95,75%. Accuracy of IC was 96,12%. In the comparative cost analysis, the release time of results for OSNA doubled that of IC and was associated with an increased cost of € 370.ConclusionsIC has been stated as a good technique for intraoperative cancer involvement SN with high sensitivity and NPV compared to the OSNA assay. It allows keeping the whole node tissue and thus the possibility of improved histopathological evaluation, which can be useful for adjuvant, and offers the advantage of being less time consuming. Cost analysis shows a higher cost for OSNA, which may exceed the benefit of sorting out false negatives from IC.     

Proteins of the retinoblastoma pathway,FEN1 and MGMT are novel potential prognostic biomarkers in pancreatic adenocarcinoma

Background

We studied the expression of some major proteins involved in cell-cycle regulation and DNA repair, the roles of which are not well known in pancreatic ductal adenocarcinoma (PDAC), but which have a significant impact on carcinogenesis of many other cancers.

Survival impact of capsule rupture in stage I clear cell carcinoma of the ovary in comparison with other histological types

Objective

We analyzed a large number of stage I clear cell carcinoma of the ovary (CCC) patients to estimate the survival impact of the capsule status in stage I CCC patients, particularly in comparison with non-CCC patients.

Methods

Clinicopathologic data on 564 patients with stage I epithelial ovarian cancer (EOC) collected under the central pathological review system were subjected to uni- and multivariable analyses to evaluate the disease-free survival (DFS) and overall survival (OS).

Results

There was no significant difference in both the OS and DFS of CCC patients between IA and IC(ir) (intraoperative capsule rupture) {IA vs. IC(ir); OS: P = 0.1402, DFS: P = 0.2701}. In contrast, CCC patients at IC(non-ir) {IC excluding for IC(ir), such as preoperative capsule rupture, positive ascites/washing, and surface involvement} showed a poorer OS and DFS than those at IC(ir), or those at the corresponding stage in non-CCC. In multivariable analysis, the capsule status was an independent prognostic factor of a poor OS and DFS {OS: HR, 2.832; 95% CI 1.156-6.938; P = 0.023; DFS: HR, 4.327; 95% CI, 1.937-9.667; P = 0.0004)} {In contrast, non-CCC: N.S. (OS/DFS)}. Furthermore, in CCC patients, intraperitoneal recurrences were more frequently observed in IC(non-ir) CCC than IA or IC(ir) CCC (P = 0.0083) {In contrast, non-CCC: N.S.}.

Conclusion

This study suggests that CCC patients other than those with intraoperative capsule rupture show a considerable risk for mortality despite adjuvant chemotherapy.     

The prognostic value of p16 and p53 expression for survival after vulvar cancer: A systematic review and meta-analysis

The tumor suppressor proteins p16 and p53 have been suggested to have prognostic value in some human papillomavirus (HPV)-associated cancers, however, this has been less well established for vulvar cancer. The aim of this review and meta-analysis was to examine the prognostic value of p16 and p53 expression status on survival after vulvar squamous cell carcinoma (VSCC). We conducted a thorough systematic literature search of multiple databases to identify studies examining survival after histolocally verified VSCC that were tested for p16 and/or p53. A total of 18 eligible studies were included. Using a fixed-effects model we calculated study-specific and pooled hazard ratios (HRs) of 5-year overall survival (OS). In the analyses of OS, we included 475 VSCC cases tested for p16 expression of which 38% were p16 positive. The pooled HR_p16 was 0.40 (95% CI: 0.29–0.55). In addition, the majority of results from studies with adjusted analyses on the prognostic value of p16 indicated that p16 expression status could be an independent prognostic marker for OS in women diagnosed with VSCC, and the same pattern was seen for disease specific survival (DSS). We also included 310 VSCC cases tested for p53 expression of which 54% were p53 positive. The pooled HR_p53 was 1.81 (95% CI: 1.22–2.68) indicating that p53 positive VSCC have a significantly lower 5-year OS compared to p53 negative. The results in relation to p53 reported from adjusted analyses OS and on DSS and disease free survival were more equivocal. This meta-analysis and review suggests that p53 and especially p16 expression status are of prognostic importance in women diagnosed with VSCC. This may be clinically important in the future design of targeted therapy and when planning the optimal follow-up strategy. Future studies should include the combined use of biomarkers such as p16, p53 and HPV status.