Background:Lymph node density (LND) has previously been reported to reliably predict recurrence risk and survival in oral cavity squamous cell carcinoma (OSCC). This multicenter international study was designed to validate the concept of LND in OSCC.Methods:The study included 4254 patients diagnosed as having OSCC. The median follow-up was 41 months. Five-year overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS), locoregional control and distant metastasis rates were calculated using the Kaplan–Meier method. Lymph node density (number of positive lymph nodes/total number of excised lymph nodes) was subjected to multivariate analysis.Results:The OS was 49% for patients with LND⩽0.07 compared with 35% for patients with LND>0.07 (P<0.001). Similarly, the DSS was 60% for patients with LND⩽0.07 compared with 41% for those with LND>0.07 (P<0.001). Lymph node density reliably stratified patients according to their risk of failure within the individual N subgroups (P=0.03). A modified TNM staging system based on LND ratio was consistently superior to the traditional system in estimating survival measures.Conclusion:This multi-institutional study validates the reliability and applicability of LND as a predictor of outcomes in OSCC. Lymph node density can potentially assist in identifying patients with poor outcomes and therefore for whom more aggressive adjuvant treatment is needed.

We propose an improved oral cancer T staging system based on incorporation of DOI that should be considered in future versions of the AJCC staging system after external validation.

Cervical lymph node metastases reduce the overall survival of patients with oral squamous cell carcinoma (OSCC) and require a neck dissection. However, elective management of a clinical N0 neck remains a controversial topic, as there are no reliable factors available predicting cervical lymph node metastases. Recent studies suggest an impact of podoplanin expression on metastatic spread to the cervical lymph nodes. Our aim was to investigate the influence of podoplanin expression on prognosis and metastatic lymphatic spread. In our retrospective study, podoplanin expression was examined in a set of 80 patients with OSCC by immunohistochemistry. We analysed associations between the level of podoplanin expression and various clinicopathologic parameters. In 67 patients (84%), podoplanin was expressed on the tumour cells. Nineteen patients (24%) showed high levels of expression. The 5-year overall survival (31%) for patients with high levels of podoplanin expression was significantly lower (p < 0.001) than for patients with low and moderate expression of podoplanin (93% and 65%, respectively). There was an association between podoplanin expression and the frequency of cervical lymph node metastases. Cervical lymph node metastases were found in 79% of the patients with high podoplanin expression, while patients with weak podoplanin expression had metastases in only 22% (p < 0.001). None of the 13 patients without podoplanin expression had cervical lymph node metastases. We concluded that podoplanin is expressed frequently in OSCC and that podoplanin expression correlates with cervical lymph node metastases and clinical outcome.

BACKGROUND An association between the survival of patients with oral cavity squamous cell carcinoma (OCSCC) and advancements in diagnosis and therapy has not been established. METHODS This was a retrospective, longitudinal, international, population‐based study of 2738 patients who underwent resection of OCSCC during 2 different decades. Characteristics of patients from 7 international cancer centers who received treatment between 1990 and 2000 (group A; n = 735) were compared with patients who received treatment between 2001 and 2011 (group B; n = 2003). RESULTS Patients in group B had more advanced tumors and tended to develop distant metastases more frequently than patients in group A (P = .005). More group B patients underwent selective neck dissection and received adjuvant radiotherapy (P < .001). Outcome analysis revealed a significant improvement in 5‐year overall survival, from 59% for group A to 70% for group B (P < .001). There was also a significant improvement in disease‐specific survival associated with operations performed before and after 2000 (from 69% to 81%, respectively; P < .001). Surgery after 2000, negative margins, adjuvant treatment, and early stage disease were independent predictors of a better outcome in multivariate analysis. The decade of treatment was an independent prognostic factor for cancer‐specific mortality (hazard ratio, 0.42; 95% confidence interval, 0.3‐0.6). CONCLUSIONS The survival rate of patients with OCSCC improved significantly during the past 2 decades despite older age, more advanced disease stage, and a higher rate of distant metastases. The current results suggest that the prognosis for patients with OCSCC has improved over time, presumably because of advances in imaging and therapy. Cancer 2013;119:4242–4248. © 2013 American Cancer Society.

Our data confirm that nodal yield is a robust independent prognostic factor in patients undergoing END for cN0 oral SCC, and may be applied irrespective of the underlying patient population and treating institution. A minimum adequate lymphadenectomy in this setting should include at least 18 nodes.

IntroductionWithin the last decades, collagen types I and III have been established as a sufficient biomaterial for GBR and GTR procedures. They might also be an adequate matrix for soft tissue augmentations. However, collagen materials differ significantly regarding resorption time, biodegradation pattern and the invasion of inflammatory cells.The aim of the present study was to compare the biodegradation and tissue integration of native, differently processed and cross-linked collagen scaffolds in rats.MethodsFour experimental porcine collagen matrices of 1.0 mm thickness, developed for soft tissue augmentation procedures, were tested. Based on the same native dermal Type I and III collagen, native (ND, Mucoderm® prototype), specifically defatted (DD), ethylene dioxide cross-linked (ECL) and dehydrothermally cross-linked (DCL) dermis collagen (AAP/Botiss Biomaterials, Berlin, Germany) were evaluated. Two specimens of 1 × 1 cm were fixed around a non-absorbable spacer using non-absorbable sutures. After rehydration, specimens (N = 8) were randomly allocated in unconnected subcutaneous pouches on the back of 40 Wistar rats. Rats were divided into five groups (1, 2, 4, 8 and 12 weeks), including eight animals each. After each period, eight rats were sacrificed and explanted specimens were prepared for histological analysis. The following parameters were evaluated: membrane thickness as a sign of biodegradation and volume stability, cell ingrowth, vascularization, tissue integration and foreign body reaction.ResultsBiodegradation pattern of the non cross-linked collagen scaffolds differed only slightly in terms of presence of inflammatory cells and cell invasion into the matrix. In terms of biodegradation, ECL displayed a considerable slower resorption than ND, DCL and DD. Chemical cross-linking using ethylene dioxide showed a significant higher invasion of inflammatory cells.ConclusionWithin the limits of the present study it was concluded that the processing techniques influenced the collagen properties in a different intensity. Dehydrothermal cross-linking and special defatting did not notably change the biodegradation pattern, whereas cross-linking using ethylene dioxide led to significant higher volume stability of the matrix. However, ECL showed an increased inflammatory response and compromised tissue integration. Therefore, ethylene dioxide seems to be not suitable for stabilization of collagen matrices for soft tissue augmentation procedures.

Ameloblastoma is a mostly benign, but locally invasive odontogenic tumor eliciting frequent relapses and significant morbidity. Recently, mutually exclusive mutations in BRAF and SMO were identified causing constitutive activation of MAPK and hedgehog signaling pathways. To explore further such clinically relevant genotype-phenotype correlations, we here comprehensively analyzed a large series of ameloblastomas (98 paraffin block of 76 patients) with respect to genomic alterations, clinical presentation, and histological features collected from the archives of three different pathology centers in France, Germany, and Turkey. In good agreement with previously published data, we observed BRAF mutations almost exclusively in mandibular tumors, SMO mutations predominantly in maxillary tumors, and single mutations in EGFR, KRAS, and NRAS. KRAS, NRAS, PIK3CA, PTEN, CDKN2A, FGFR, and CTNNB1 mutations co-occurred in the background of either BRAF or SMO mutations. Strikingly, multiple mutations were exclusively observed in European patients, in solid ameloblastomas and were associated with a very high risk for recurrence. In contrast, tumors with a single BRAF mutation revealed a lower risk for relapse. We here establish a comprehensive landscape of mutations in the MAPK and hedgehog signaling pathways relating to clinical features of ameloblastoma. Our data suggest that ameloblastomas harboring single BRAF mutations are excellent candidates for neo-adjuvant therapies with combined BRAF/MEK inhibitors and that the risk of recurrence maybe stratified based on the mutational spectrum.

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