The aim of this study was to evaluate the effect of platelet-rich plasma (PRP) on remodeling of autologous bone grafts used for augmentation of the floor of the maxillary sinus. In five edentulous patients suffering from insufficient retention of their upper denture related to a severely resorbed maxilla, the floor of both maxillary sinus was augmented with an autologous bone graft from the iliac crest. Randomly, PRP was added to the bone graft used to augment the floor of the left or right sinus (split-mouth design). Three months after the reconstruction, bone biopsies were taken with a trephine from the planned implant sites (N=30). Subsequently, three implants were placed in the left and right posterior maxilla. Microradiograms were made of all biopsies (N=30), whereafter the biopsies were processed for light microscopic examination. In addition, clinical parameters were scored. Wound healing was uneventful, clinically no difference was observed between the side treated with PRP or not. Also microradiographical and histomorphological examination of the biopsies revealed no statistical difference between the PRP- and non-PRP side. One implant placed in the PRP side of the graft was lost during the healing phase. Implant-retained overdentures were fabricated 6 months after implantation. All patients functioned well (follow-up 20.2+/-4.3 months). In this study, no beneficial effect of PRP on wound healing and bone remodeling was observed. It is posed that PRP has no additional value in promoting healing of grafted non-critical size defects.

The development of second primary tumors has a negative impact on the prognosis of head and neck squamous cell carcinoma. Previously, we detected genetically altered and tumor-related mucosal lesions in the resection margins in 25% of unselected head and neck squamous cell carcinoma patients (Tabor MP, Brakenhoff RH, van Houten VMM, Kummer JA, Snel MHJ, Snijders PJF, Snow GB, Leemans CR, Braakhuis BJM: Persistence of genetically altered fields in head and neck cancer patients: biological and clinical implications. Clin Cancer Res 2001, 7: 1523-1532). The aim of this study was to determine whether first and second primary tumors are clonally related and originate from a single genetically altered field. From 10 patients we analyzed the first tumor of the oral cavity or oropharynx, the >3-cm remote second primary tumor, and the mucosa from the tumor-free margins from both resection specimens. We compared TP53 mutations and loss of heterozygosity profiles using 19 microsatellite markers at chromosomes 3p, 9p, 13q, and 17p. In all patients, genetically altered mucosal lesions were detected in at least one resection margin from both first and second primary tumor. Evidence for a common clonal origin of the first tumor, second primary tumor, and the intervening mucosa was found for at least 6 of 10 patients. Our results indicate that a proportion of multiple primary tumors have developed within a single preneoplastic field. Based on different etiology and clinical consequences, we propose that independent second primary tumors should be distinguished from second field tumors, that arise from the same genetically altered field the first tumor has developed from.

A parotid biopsy has a diagnostic potential comparable with that of a labial biopsy in the diagnosis of pSS, and may be associated with less morbidity.

Distant metastases of ACC of the salivary glands occur most often in the lungs. Although these lung metastases are the first to occur, these patients die later than patients with distant metastases in other organs. The value of annual chest films or other tests for the presence of distant metastases during follow-up after surgical removal of an ACC seems rather questionable.

Histological grading of epithelial dysplasia in the oral cavity and oropharynx is used to predict the risk for cancer and to determine the treatment strategy. This grading, however, is subjective and not well reproducible. Recent publications have shown that molecular markers are promising in cancer risk assessment. The aim of the present study was to compare classical histological and molecular grading and to relate these to the proliferation rate by quantitative assessment of Ki-67 staining. Forty-three samples were analysed from the margins of patients who had undergone resection of their squamous cell carcinoma in the oral cavity/oropharynx. Three experienced pathologists performed the histological grading. With the consensus score, 12 samples were classified as normal and 31 as dysplastic (21 mild, six moderate, and four severe). Loss of heterozygosity (LOH) was assessed in the same samples with 15 microsatellite markers at chromosomes 3p, 9p, 17p, 8p, 13q, and 18q, and was present in 28 of the 43 samples. Twenty-four of the 28 cases (86%) with LOH were classified as dysplastic and four as normal. All ten samples with moderate and severe dysplasia and 14 of 21 samples with mild dysplasia contained LOH. In four of 12 biopsies classified as normal, LOH was found. A very striking and significant difference of the Ki-67 index was observed between LOH-positive and LOH-negative cases, 36.6 +/- 11.1% versus 19.4 +/- 2.8% positive cells, respectively. In mild dysplasia, 13 of 14 lesions containing LOH had a higher Ki-67 index than all seven lesions without LOH. Thus, in the oral cavity/oropharynx, LOH is more frequently found in the histologically higher-grade lesions (moderate dysplasia or worse) and in the lower grade lesions when a high proliferation rate is present. Assessment of proliferation with Ki-67 is a better surrogate for LOH than histological grading.

Within the periodontal stroma, citrullination is an inflammation-depended process. In periodontal epithelium, citrullination is a physiological process. Additional citrullinated proteins are formed in periodontitis, apparently similar to those formed in RA-affected synovial tissue. Periodontitis induced citrullination may play a role in the aetiology of rheumatoid arthritis.

Purpose: To find molecular markers from expression profiling data to predict recurrence of laryngeal cancer after radiotherapy.Experimental Design: We generated gene expression data on pre-treatment biopsies from 52 larynx cancer patients. Patients developing a local recurrence were matched for T-stage, subsite, treatment, gender and age with non-recurrence patients. Candidate genes were then tested by immunohistochemistry on tumor material from a second series of 76 patients. Both series comprised early stage cancer treated with radiotherapy alone. Finally, gene expression data of eight larynx cancer cell lines with known radiosensitivity were analyzed.Results: Nineteen patients with a local recurrence were matched with 33 controls. Gene sets for hypoxia, proliferation and intrinsic radiosensitivity did not correlate with recurrence, whereas expression of the putative stem cell marker CD44 did. In a supervised analysis, probes for all three splice variants of CD44 on the array appeared in the top 10 most significantly correlated with local recurrence. Immunohistochemical analysis of CD44 expression on the independent validation series confirmed CD44's predictive potential. In 8 larynx cancer cell lines, CD44 gene expression did not correlate with intrinsic radiosensitivity although it did correlate significantly with plating efficiency, consistent with a relationship with stem cell content.Conclusions: CD44 was the only biological factor tested which significantly correlated with response to radiotherapy in early stage larynx cancer patients, both at the mRNA and protein levels. Further studies are needed to confirm this and to assess how general these findings are for other head and neck tumor stages and sites. Clin Cancer Res; 16(21); 5329-38. ©2010 AACR.

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