Prognostic impact of the loss of E-cadherin and de novo expression of N-cadherin at the invasive front of primary and recurrent oral squamous cell carcinoma.

The epithelial-mesenchymal transition (EMT) is a biological mechanism in multiple pathophysiological diseases. Related alterations in cadherin expression play a crucial role in carcinogenesis, progression, angiogenesis, and immune response. EMT cells exhibit a transition from an epithelial to a mesenchymal phenotype (cadherin-switch). This process is characterized by the de novo development of N-cadherin (N-CAD), which replaces E-cadherin (E-CAD) and signifies an increased migratory capacity and malignant transformation. The cadherin switch is a hallmark of EMT and has been studied in various cancer entities. We predicted that the cadherin switch in the primary and recurrent oral squamous cell carcinoma (re-OSCC) tissues is an inherent characteristic of the tumor, affects the biologic behavior, and further reflects the post-recurrence survival outcome of these patients. Survival outcome was analyzed by calculating the post-recurrence survival of the high-risk group and correlating the standardized h-score-based IHC expression of both cadherin types with the clinical follow-up. 94 patients with re-OSCC were observed within the cohort. Tissue samples from both primary and recurring tumors were collected. There was a significant association between loss of E-CAD expression and both oral cancer-specific and overall survival, (HR=2.72, CI:1.50-4.95, p=0.001) and (HR=3.84, CI:1.93-7.63, p=0.001), respectively, for expression loss higher than 60%. There was no statistically significant correlation between N-CAD de novo expression and Overall, oral cancer-specific and disease-free post-recurrence survival. The current study clearly shows that cadherin-switch, identified as E-CAD loss and N-CAD de novo expression in the invasion front of a re-OSCC, appears to be an inherent histological hallmark that does not change from primary manifestation to recurrence within the same tumor, regardless of the form of adjuvant therapy used for the primary tumor. The loss of E-CAD expression in re-OSCC is an independent risk factor for poor survival, and may be used to stratify therapy and de/escalate the multimodal treatment.

Long-term outcome of sporadic and FAP-associated desmoid tumors treated with high-dose selective estrogen receptor modulators and sulindac: a single-center long-term observational study in 134 patients.

Aim of this study is to evaluate the outcome of long-term conservative treatment with sulindac and high-dose selective estrogen receptor modulators (SERMs) for sporadic and FAP-associated desmoid tumors. Desmoids are very rare tumors in the general population but occur frequently in FAP patients, being encountered in 23-38 %. Treatment of desmoids is still most controversial since response cannot be predicted and they are prone to develop recurrence. This study included all desmoid patients that were treated and followed at our institution and had completed at least 1 year of treatment. Response was defined as stable size or regression of desmoid size between two CT or MRI scans. A total of 134 patients were included. 64 (47.8 %) patients had a confirmed diagnosis of FAP, 69 (51.5 %) patients were sporadic. Overall 114 (85.1 %) patients showed regressive or stable desmoid size. Patients with previous history of multiple desmoid-related surgeries showed less-favorable response. The mean time to reach at least stable size was 14.9 (±9.1) months. After regression or stabilization, medication was tapered in 69 (60.5 %) of the treated patients with only one long-term recurrence after >10 years. The results of this study fortify the role of sulindac and high-dose SERMs as an effective and safe treatment for both, sporadic and FAP-associated desmoid tumors. While invasive treatment frequently results in high recurrence rates, high morbidity and high mortality, this conservative treatment is successful in most patients. The recurrence rate is negligible with no desmoid-related mortality in this large series. Therefore surgical resection, especially for mesenteric desmoids, should be deferred favoring this convincingly effective, well tolerated regimen.

Agreement of multislice CT angiography and MR angiography in assessing the degree of carotid artery stenosis in consideration of different methods of postprocessing.

OBJECTIVE: We investigated the agreement of multislice computed tomography angiography (CTA) and magnetic resonance angiography (MRA) in the quantitative measurement of carotid artery stenosis. The dependency of the agreement of the chosen postprocessing procedures was also investigated. METHODS: Fifty consecutive symptomatic patients were included in this study. In all patients, a CTA was performed with a 16-slice CT scanner. Within 30 days, the extracranial vessels were examined using a combined time-of-flight and contrast-enhanced MRA. The CT data sets were used to calculate the degree of stenosis according to the North American Symptomatic Carotid Endarterectomy Trial, European Carotid Surgery Trial, and Common Carotid methods by means of the 1-mm thick, transverse raw data (RD), a sagittal maximum-intensity projection reconstruction, and sagittal multiplanar reconstruction. In addition, a semiautomated analysis was done using a specialized postprocessing software. For all combinations of postprocessing procedures and methods of calculating the degree of stenosis, the correlation coefficient and the agreement based on Bland/Altman plots were calculated. RESULTS: Eleven of the 100 primarily included carotid arteries could not be evaluated. The correlation coefficients for all combinations were comparable and lied in the interval between 0.932 and 0.787. The best correlation was found for the combination of RD/sagittal multiplanar reconstruction and ECST method. The evaluation of the agreement gave a systematic overestimation of CTA between 1.9% and 10.7% with a 95% confidence interval between +/-26.7% and +/-43.3%. With the semiautomated postprocessing software, additional 33 vessels could not be evaluated. The agreement of the calculated degrees of stenoses was worse than that of the planar procedures. CONCLUSIONS: CTA and MRA had a feasible agreement in measuring the degree of stenosis of the carotid arteries. The best result could be obtained for the evaluation of the RD and the NASCET method. In this case one has to take into account a systematic overestimation of CTA of 1.9%. The combination with an additional reconstructive postprocessing procedure did not improve the result but might be useful for the radiologist to identify the location of the closest narrowing.