Pattern of invasion and lymphovascular invasion in squamous cell carcinoma of the floor of the mouth: an interobserver variability study.

AIMS: Lymphovascular invasion (LVI) and the histological pattern of invasion (POI) at the invasive tumour front have been reported as adverse prognosticators in oral squamous cell carcinoma (SCC). However, assessment of these parameters is hampered by variation in the criteria used for their evaluation. Our objective was to evaluate interobserver variability in the assessment of the POI and LVI in SCC of the floor of the mouth (FOM), and to study the impact of the POI on clinical outcomes by using varying quantitative cut-offs. METHODS AND RESULTS: Fifty-eight cases of FOM SCC were independently evaluated for the POI and LVI by three pathologists. Interobserver variability was analysed by the use of Fleiss kappa statistics. Interobserver agreement was substantial for the assessment of LVI [κ = 0.64, 95% confidence interval (CI) 0.60-0.68]. Interobserver agreement was moderate for evaluation of the POI with a 50% cut-off (κ = 0.58, 95% CI 0.54-0.62), a 20% cut-off (κ = 0.58, 95% CI 0.54-0.62) cut-off, and worst POI (κ =0 .43, 95% CI 0.39-0.46). A consensus diagnosis of the POI was a significant predictor of locoregional recurrence (LRR), disease-specific survival (DSS) and overall survival (OS) on univariate analysis when a 50% cut-off was used (LRR, P = 0.01; DSS, P = 0.01; OS, P = 0.01) and when a 20% cut-off was used (LRR, P = 0.02; DSS, P = 0.02; OS, P = 0.03), but was not significant when worst POI was used (LRR, P = 0.18; DSS, P = 0.16; OS, P = 0.17). CONCLUSIONS: Interobserver agreement in the diagnosis of LVI was substantial. The POI at the 50% and 20% cut-offs is moderately reproducible, and has prognostic value in FOM SCC. Further studies are necessary to establish the optimum quantitative cut-off for the POI.

Endometriosis of the Small Bowel: A Diagnostic Enigma.

Endometriosis refers to the implantation and proliferation of endometrial tissue outside the uterus. Small bowel endometriosis is an uncommon location for endometrial deposits and when present, it can pose diagnostic difficulty. Here, we present a case of a 50-year-old female with small bowel endometriosis who suffered from recurrent attacks of colicky abdominal pain for few months. Her cross-sectional investigations remained largely inconclusive. Ultimately, she underwent diagnostic laparoscopy which was diagnostic and therapeutic.

HDAC6 Degradation Inhibits the Growth of High-Grade Serous Ovarian Cancer Cells.

Histone deacetylase 6 (HDAC6) is a unique histone deacetylating enzyme that resides in the cell cytoplasm and is linked to the modulation of several key cancer related responses, including cell proliferation and migration. The promising anti-cancer response of the first-generation HDAC6 catalytic inhibitors continues to be assessed in clinical trials, although its role in high grade serous ovarian cancer is unclear. This study investigated HDAC6 tumor expression by immunohistochemistry in high-grade serous ovarian cancer (HGSOC) tissue samples and a meta-analysis of HDAC6 gene expression in ovarian cancer from publicly available data. The pharmacological activity of HDAC6 inhibition was assessed in a patient-derived model of HGSOC. HDAC6 was found to be highly expressed in HGSOC tissue samples and in the patient-derived HGSOC cell lines where higher HDAC6 protein and gene expression was associated with a decreased risk of death (hazard ratio (HR) 0.38, (95% confidence interval (CI), 0.16-0.88; p = 0.02); HR = 0.88 (95% CI, 0.78-0.99; p = 0.04)). Similarly, the multivariate analysis of HDAC6 protein expression, adjusting for stage, grade, and cytoreduction/cytoreductive surgery was associated with a decreased risk of death (HR = 0.19 (95% CI, 0.06-0.55); p = 0.002). Knock-down of HDAC6 gene expression with siRNA and protein expression with a HDAC6 targeting protein degrader decreased HGSOC cell proliferation, migration, and viability. Conversely, the selective inhibition of HDAC6 with the catalytic domain inhibitor, Ricolinostat (ACY-1215), inhibited HDAC6 deacetylation of α-tubulin, resulting in a sustained accumulation of acetylated α-tubulin up to 24 h in HGSOC cells, did not produce a robust inhibition of HDAC6 protein function. Inhibition of HGSOC cell proliferation by ACY-1215 was only achieved with significantly higher and non-selective doses of ACY-1215. In summary, we demonstrated, for the first time, that HDAC6 over-expression in HGSOC and all ovarian cancers is a favorable prognostic marker. We provide evidence to suggest that inhibition of HDAC6 catalytic activity with first generation HDAC6 inhibitors has limited efficacy as a monotherapy in HGSOC.

Excisional treatments of the cervix and effect on subsequent fertility: a retrospective cohort study.

OBJECTIVE: Concerns exist regarding the impact of excisional treatments for cervical intraepithelial neoplasia (CIN) on subsequent pregnancy outcome yet few studies have addressed fertility following surgery. STUDY DESIGN: Retrospective cohort study. Set in the colposcopy service of National Maternity Hospital. A postal questionnaire was sent to 3590 women of reproductive age who attended colposcopy from 2001 to 2007; 1795 of these had at least one excisional treatment (surgical group) and 1795 had no treatment (non-surgical group). Records were reviewed to confirm the clinical details and volume of tissue excised. The main outcome measures were pregnancy and fertility rates as well as time to conception correlated with volume of tissue excised. Students' t-test, Mann-Whitney U-test, spearman correlation and Kruskal-Wallis tests were used during the analysis. RESULTS: 1355 Women (37.7%) responded. 537 Women had no treatment and 818 had at least one excision. A subsequent pregnancy was reported in 730 women (434 surgical and 296 non-surgical groups). No difference was detected between the groups in the reported pregnancy rates (p=0.56), the time to conception (p=0.37) or fertility problems (p=0.89). The volume of the excision did not affect fertility rates or time to conception. There were fewer pregnancies in women following a cold knife cone or more than one LLETZ treatment-significant surgery, (p=0.004) but no difference in their reported time to conception (p=0.54). CONCLUSIONS: One excisional treatment for CIN does not appear to affect subsequent fertility. Our study showed no delay in conception and no increased risk of problems conceiving in this group, even when controlling for the volume and depth of tissue removed. Women should be reassured by these results. Further work is required to evaluate the effect of cold knife cone biopsy and repeated LLETZ procedures on subsequent fertility.

Spinal diastematomyelia: a means of identification of charred remains.

The purpose of medico legal autopsy examination is the positive identification of the deceased in addition to the determination of the cause of death in most jurisdictions and additionally the manner of death in many jurisdictions. Notwithstanding the established and recognised value of DNA analysis in human identification, in the case of significant and extensive thermal injury in victims of fire, DNA analysis may prove difficult. Fire fatality identification can be assisted by alternative methods in this situation, including correlation between ante mortem and post mortem radiological investigations, identification of rare medical disease and or dental record examinations, where available. We describe a case where identification of charred human remains from a car fire was securely determined by demonstration of the presence of a rare congenital abnormality of the spinal cord, Diastematomyelia.