Emerging Role of Decoy Receptor-2 as a Cancer Risk Predictor in Oral Potentially Malignant Disorders.

The aim of this study was to evaluate the expression of the senescence markers, Decoy Receptor 2 (DcR2) and Differentiated Embryo-Chondrocyte expressed gen 1 (DEC1), in oral potentially malignant disorders (OPMDs) to ascertain their possible association with oral cancer risk. The immunohistochemical analysis of DcR2 and DEC1 expression (along with p16 and Ki67 expression) was carried out in 60 patients with clinically diagnosed oral leukoplakia. Fifteen cases (25%) subsequently developed an invasive carcinoma. Correlations between protein marker expression, histological grade and oral cancer risk were assessed. DcR2, DEC1 and Ki67 protein expressions were found to correlate significantly with increased oral cancer risk, and also with an increased grade of dysplasia. Multivariate analysis demonstrated that DcR2 and Ki67 expression are independent predictors of oral cancer development. Our results evidence for the first time the potential of DcR2 as an early biomarker to assess oral cancer risk in patients with oral leukoplakia (HR = 59.7, p = 0.015), showing a superior predictive value to histology (HR = 4.225, p = 0.08). These findings reveal that the increased expression of DcR2 and DEC1 occurred frequently in OPMDs. In addition, DcR2 expression emerges as a powerful biomarker for oral cancer risk assessment in patients with oral leukoplakia.

Risk factors associated with fixation-related complications in microsurgical free flap reconstruction of the mandible.

BACKGROUND: Hardware complications (loosening of screws, infection, or exposure of the plate) in mandibular reconstruction with vascularized osseous free flaps impose significant morbidity, and frequently require revision surgery. Purpose of this study was to identify possible contributing factors for hardware complications. METHODS: This is a retrospective cohort study involving case series of patients who underwent microvascular mandible reconstructions between 2000 and 2020. Patient demographics, pathological, clinical, and treatment-related factors were analyzed in univariate and multivariate analyses. RESULTS: Ninety-one patients were enrolled, encompassing 63 reconstructions with fibular free flaps, 26 reconstructions with scapular, and 2 reconstructions with iliac flaps. Rate of hardware complications and plate exposure was 14.3% and 7.7%, respectively, with a median follow-up time for extrusion of 29 months. In univariate analysis, preoperative radiotherapy (odds ratio [OR] = 6.57, p = .01), and secondary mandible reconstruction (OR = 4.3, p = .04) were significant predictors of hardware complications, and plate exposure was most frequently found in secondary reconstruction (37.5%, OR = 11.8, p = .04). Hypertension was the most commonly found comorbidity (24%), and it trended toward significance regarding plate exposure (p = .05). Only secondary mandible reconstruction was associated with osteosynthesis complications (OR = 12.53, p = .01) and plate exposure (OR = 23.86, p = .005) on multivariate analysis, while preoperative radiation therapy did not retain its relevance on plate exposure. CONCLUSION: Secondary mandible reconstructions with vascularized osseous free flaps have a higher risk of osteosynthesis complications than primary reconstructions.

Functional results of swallowing and aspiration after oral cancer treatment and microvascular free flap reconstruction: A retrospective observational assessment.

This study aimed to assess the functional swallowing outcomes in cohort of oral cancer patients treated with tumor resection and reconstruction by means of microvascular free flaps. Duration from onset to the last examination was classified into three periods: less than 12 months, from 13 to 24 months, and more than 24 months. Type of feeding, dysphagia, and laryngeal aspiration were the dependent variables, and the study was mainly focused on the data from the multivariate analysis. Fifty-one patients were included in the study. Twenty-one patients had dysphagia, 11 showed stasis in vallecula and pyriform sinuses, 9 experienced laryngeal penetration, and 8 aspirations. Surgery combined with radiochemotherapy was associated with a higher prevalence of dysphagia (p = 0.03). Frequency of dysphagia was higher in the first year after treatment and less frequent after 24 months (p = 0.003). Dysphagia was associated with laryngeal penetration (p = 0.001), and this with aspiration (p < 0.0005). In conclusion, as it seems that the method of reconstruction has a major influence on swallowing, when there are relevant alternatives in the way the reconstruction is done, always the approach should be chosen that reduces dysphagia to a minimum.

Frequent Alteration of Annexin A9 and A10 in HPV-Negative Head and Neck Squamous Cell Carcinomas: Correlation with the Histopathological Differentiation Grade.

The annexin protein superfamily has been implicated in multiple physiological and pathological processes, including carcinogenesis. Altered expression of various annexins has frequently been observed and linked to the development and progression of various human malignancies. However, information is lacking on the expression and clinical significance of annexin A9 (ANXA9) and A10 (ANXA10) in head and neck squamous cell carcinomas (HNSCC). ANXA9 and ANXA10 expression was evaluated in a large cohort of 372 surgically treated HPV-negative HNSCC patients and correlated with the clinicopathologic parameters and disease outcomes. Down-regulation of ANXA9 expression was found in 42% of HNSCC tissue samples, compared to normal epithelia. ANXA9 expression in tumors was significantly associated with oropharyngeal location and histological differentiation grade (P < 0.001). In marked contrast, ANXA10 expression was absent in normal epithelium, but variably detected in the cytoplasm of cancer cells. Positive ANXA10 expression was found in 64% of tumors, and was significantly associated with differentiation grade (P < 0.001), being also more frequent in oropharyngeal tumors (P = 0.019). These results reveal that the expression of both ANXA9 and ANXA10 is frequently altered in HNSCC and associated to the tumor differentiation grade, suggesting that they could be implicated in the pathogenesis of these cancers.

Clinicopathologic and Surgical Study of Pleomorphic Adenoma of the Parotid Gland: Analysis of Risk Factors for Recurrence and Facial Nerve Dysfunction.

PURPOSE: To determine whether clinicopathologic or surgical features are risk factors for recurrence and facial nerve dysfunction in pleomorphic adenoma (PA) of the parotid gland. PATIENTS AND METHODS: The records of 198 patients surgically treated for a PA of the parotid gland from 1999 through 2013 were retrospectively reviewed to identify patients who developed a tumor recurrence. The Fisher exact test and Mann-Whitney U test were used to analyze patient characteristics between recurrent and non-recurrent PAs. Logistic regression was used to determine the risks of recurrence and facial nerve dysfunction. RESULTS: Twenty-three patients (11.6%) developed a recurrence. Patients with tumor recurrence were notably younger than patients without recurrence. Of the 14 patients who underwent enucleation, 11 (78.6%) developed residual disease, as did 10 of 165 patients (6%) managed by a superficial parotidectomy (P < .0005). Furthermore, the risk of residual disease was 9.3 to 21.6 times higher in patients who underwent enucleation than in those who underwent a total or superficial parotidectomy. For tumor histology, recurrence was observed in 3 (15.8%) of the 19 cellular types, 18 (11.5%) of 157 classic cases, and 1 (4.8%) of 21 myxoid cases (P = .5). The risk of recurrence with positive resection margins was 49 times higher than with negative margins (P = .001). CONCLUSION: Young age, enucleation, and positive margins are risk factors for residual pleomorphic adenoma, and surgical technique and histomorphologic features are associated with increased facial nerve dysfunction.

Dysregulation of Mir-196b in Head and Neck Cancers Leads to Pleiotropic Effects in the Tumor Cells and Surrounding Stromal Fibroblasts.

The miR-196 family members have been found dysregulated in different cancers. Therefore, they have been proposed as promising biomarkers and therapeutic targets. This study is the first to investigate the role of miR-196b in the development and progression of head and neck squamous cell carcinomas (HNSCC), and also the impact on the surrounding tumor microenvironment. Increased miR-196b levels were detected in 95% of primary tumors and precancerous lesions, although no significant differences were observed between non-progressing versus progressing dysplasias. Furthermore, increased levels of both miR-196a and miR-196b were successfully detected in saliva samples from HNSCC patients. The functional consequences of altered miR-196 expression were investigated in both HNSCC cell lines and cancer-associated fibroblasts (CAFs) by transfection with specific pre-miR precursors. Results showed that both miR-196a and miR-196b elicit cell-specific responses in target genes and downstream regulatory pathways, and have a distinctive impact on cell proliferation, migration and invasion. These data reveal the early occurrence and prevalence of miR-196b dysregulation in HNSCC tumorigenesis, suggesting its utility for early diagnosis and/or disease surveillance and also as a non-invasive biomarker in saliva. The pleiotropic effects of miR-196a/b in HNSCC cell subpopulations and surrounding CAFs may complicate a possible therapeutic application.

Modified facelift approach combined with a superficial musculoaponeurotic system flap in the treatment of benign parotid tumors.

PURPOSE: The purpose of this study was to investigate the adequacy of a modified facelift incision combined with an SMAS flap for the resection of benign parotid lesions in terms of cosmesis and incidence of Frey's syndrome. MATERIALS AND METHODS: A hundred patients who underwent superficial parotidectomy were divided into 2 groups according to approach: Blair incision (57 cases) and modified facelift incision (43 cases). In the latter group, 36 patients were reconstructed with a superficial musculoaponeurotic system (SMAS) flap. During follow-up, patients were asked to rate their satisfaction with their postoperative appearance using a 1 to 3 scale. RESULTS: Clinical Frey's syndrome was present in 8.5% of patients with SMAS flap, and in 19% patients without SMAS flap (p = 0.16). The average cosmetic outcome score for patients who underwent a modified facelift approach combined with an SMAS flap was 2.87, whereas patients whose tumors were approached through a Blair incision reported a lower score of 2.1 (p < 0.005). CONCLUSION: A modified facelift incision combined with an SMAS flap improved the cosmetic appearance of patients who underwent extrafacial or superficial parotidectomy. In addition, this flap seems to reduce the occurrence of Frey's syndrome.

Relevance of level IIb neck dissection in oral squamous cell carcinoma.

BACKGROUND: The purpose of this study was to determine the prevalence of level IIb metastasis in patients with oral squamous cell carcinomas (OSCCs). MATERIAL AND METHODS: A prospective analysis of 56 patients with OSCC who underwent surgical treatment of the primary lesion with simultaneous neck dissection was performed. During neck dissection, level IIb lymph nodes were separately removed and processed. Neck dissection was bilateral in 26 patients (46%) and unilateral in 30 patients (54%). RESULTS: The mean number of nodes found in the level IIb specimens was 4.7 (range: 0-8 nodes). The prevalence of metastasis at level IIb was 0% in pN0 necks and 3.4% in pN+ necks, with an overall prevalence of 1.8%. A significant association between metastasis to level IIb and type of neck dissection was observed. There were no isolated metastases to level IIb without the involvement of other nodes in the remaining neck specimen. Four regional recurrences were observed during follow-up. CONCLUSIONS: Based on our findings, we suggest that dissection of the level IIb region in patients with OSCC may be required only in patients with multilevel neck metastasis or if level IIa metastasis is found intraoperatively.

Clinical outcomes after the use of complete autologous oral mucosa equivalents: preliminary cases.

OBJECTIVE: Previously, we reported how to obtain complete autologous oral mucosa equivalents (CAOMEs) composed of an autologous plasma scaffold and fibroblasts together with immature keratinocytes able to build an oral epithelium with a structure similar to that of the oral mucosa. In this study, we present the clinical outcomes after applying our CAOMEs as grafts. STUDY DESIGN: Four patients who needed a CAOME to restore a defect of oral mucosa were selected. Two of the patients suffered from ankyloglossia, and the other 2 required a restoration of the keratinized gum of the alveolar rim. To assess the outcomes, the scale designed by Ewers et al. was used. RESULTS: Clinical and functional improvements were achieved in the patients with ankyloglossia. In cases of gum restoration, the mucosa was regenerated and a prosthetic restoration with implants was achieved. CONCLUSIONS: The results obtained points to the potential use of CAOME in intraoral lining.

Use of autologous skin equivalents with artificial dermal matrix (integra) in donor site coverage in radial forearm free flaps: preliminary cases.

PURPOSE: The radial forearm flap is one of the most commonly used methods for intraoral reconstruction in oral carcinoma surgery. One of its disadvantages is the residual functional and unaesthetic defect in the donor site. The objective of this report is to describe preliminary cases of a novel method to cover such donor sites based on the use of autologous skin equivalents (ASEs) and an artificial dermal matrix (Integra, Prim, Barcelona, Spain). MATERIALS AND METHODS: The donor sites of 2 patients were treated with the artificial dermal matrix after raising a radial forearm flap. A skin biopsy and a blood sample were taken to construct an ASE. After 3 weeks, the ASE was applied over the dermal template and left to heal. The functional and esthetic results were recorded. RESULTS: Good functional and esthetic results were achieved, with correct wrist motility, although a natural skin color could not be achieved. Neither the Integra nor the ASE was rejected. Total wound coverage was achieved at 4 months, and completely normal skin was observed at 6 months. CONCLUSIONS: This technique of combining an artificial dermal matrix with an ASE could be an alternative method to cover the donor sites of radial forearm flaps.

[Superficial angiomyxoma of the parotid region and review of the literature]. / Angiomixoma superficial de la región parotídea y revisión de la literatura.

Superficial angiomyxoma (SA) is a rare benign cutaneous neoplasm first described by Allen et al in 1988. To the best of our knowledge, we report the first case of superficial angiomyxoma located in the parotid region. We also stress the importance of distinguishing this entity from other lesions that may be involved in this location such as cutaneous neoplasms, parotid tumours or cysts. We emphasise the need to rule out the Carney complex, which has been associated with these tumours.

Survival after free flap reconstruction in patients with advanced oral squamous cell carcinoma.

PURPOSE: The purpose of the present study was to assess the effect of free-flap reconstruction on the survival of patients treated for oral squamous cell carcinoma. PATIENTS AND METHODS: The present study was based on a retrospective cohort of 98 patients. Of the 98 patients, 49 underwent surgical reconstruction with microvascular tissue transfer (test group) and in 49 (control group), only local or regional flaps were used. RESULTS: For the free-flap group, the average follow-up period was 34.6 months. For the control group, the average follow-up was 39.8 months. At the end of the follow-up period, 23 (47%) and 33 (67.3%) patients had died of oral squamous cell carcinoma in the microvascular reconstructive and control group, respectively. The difference in the final status between the 2 groups was statistically significant (P = .03). In the free-flap group, the mean and median survival time was 65 and 60 months. In the locoregional flap group, the mean and median survival time was 54 and 24 months, respectively. No difference was seen in the survival time between the free-flap and local flap groups (P = .2). Univariate Kaplan-Meier analysis revealed that positive surgical margins were significantly associated with shortened survival in the free-flap group and that recurrence was significant in both reconstructive groups. On multivariate Cox regression analysis, the status of the resection margin (P = .07) and tumor recurrence (P < .0005) showed a significant relationship with survival. CONCLUSION: Patients with free-flap reconstruction of surgically created defects after oral cancer resection showed a trend toward better 5-year survival.

Clinical and immunohistochemical analysis of orbital metastasis from prostate carcinoma.

Orbital tumors can present with different symptoms, especially ophthalmic disturbances. We describe 1 patient with an orbital metastasis from prostate carcinoma presenting with proptosis and give details of his presentation, diagnostic tools, and treatment. This is a rare case. Possible ocular spread of prostate adenocarcinoma and the diagnostic techniques used are discussed. It is stressed that immunohistochemical studies and comparison with primary tumor may be essential for a definitive diagnosis. The treatment of prostate orbital metastases is also reviewed.

Posttraumatic frontal mucocele.

Mucoceles of the frontal sinus are expansive cysts filled of the mucus secreted by goblet cells interspersed in the ciliated mucosa. The aim of this article was to present a case of a frontal mucocele that was developed in a 31-year-old man 19 years after having had a frontal sinus fracture. This is a rare entity. Frontal sinus fractures must be treated by a multidisciplinary team to avoid all possible sequelae. An adequate primary management of frontal sinus fractures is essential to prevent complications. This may include conservative attitude, reduction and fixation with miniplates, obliteration, cranialization, or grafting. Removal of any rest of epithelium is mandatory in this sense.

Microvascular free tissue transfer for tongue reconstruction after hemiglossectomy: a functional assessment of radial forearm versus anterolateral thigh flap.

PURPOSE: The purpose of this study was to evaluate tongue function and donor site morbidity in patients with oral cancer surgically treated and reconstructed with radial or anterolateral thigh free flaps. PATIENTS AND METHODS: Twenty patients underwent primary reconstruction after hemiglossectomy between January 2002 and June 2004. Ten patients were reconstructed using a free forearm flap and the remaining with an anterolateral thigh flap. Eight patients on each group underwent postoperative radiotherapy (average, 60 Gy). All of them were followed postoperatively to determine after 6 months their functional outcome as it related to speech, deglutition, tongue mobility, and donor site morbidity. The intelligibility, deglutition, and tongue mobility were each scored on a scale ranging from 1 to 7 by an independent investigator. Data were analyzed by the 2-tail Mann-Whitney U test. RESULTS: No differences in mean speech intelligibility, tongue mobility, or deglutition mean scores were seen between radial forearm flap and anterolateral thigh flap (P > .05). In all anterolateral thigh flap-treated cases, the donor site was closed directly and no complications were seen. However, in all forearm flaps donor site closure was carried out with skin grafts and dorsal forearm splinting was applied for 1 week postoperatively. In 4 cases a partial skin graft failure was observed and donor sites healed for second intention. CONCLUSION: Anterolateral thigh flap, with its versatility in design, long pedicle with a suitable vessel diameter, and low donor site morbidity, could be the ideal flap for hemiglossectomy defect reconstruction.

Immunoexpression and prognostic significance of TIMP-1 and -2 in oral squamous cell carcinoma.

Matrix metalloproteinases (MMPs) are proteolytic enzymes that are capable of degrading different substrates within the extracellular matrix, and which are believed to be crucial for tumor invasion and metastasis. Tissue inhibitors of MMPs (TIMPs) can inhibit the action of MMPs but also can show a paradoxical poor prognostic effect. In order to evaluate the prognostic significance of TIMPs, we studied the expression of TIMP-1 and -2 in series of 68 oral squamous cell carcinomas (OSCC) by immunohistochemistry. Expression of TIMP-1 was detected in 45 cases (66.2%). In all of these TIMP-1 was expressed in tumoral tissue, and in 19 of them also in the surrounding stroma. In cancer tissue, TIMP-1 was observed in three patterns: homogeneous, central and irregular. Immunoreactivity for TIMP-2 was detected in 38 cases (56%) in tumoral tissue and 9 (13.2%) in the stroma. The expression pattern of TIMP-2 was the same three as TIMP-1 and one more: invasive front of tumoral nests. TIMP-1 expression was not correlated with clinical or pathological parameters. However, TIMP-2 was significantly correlated with T stage (p=0.03), TNM stage (p=0.01), local recurrence (p=0.04), and poor survival (p=0.03, odds ratio=2.75). TIMP-1 and TIMP-2 were significantly correlated with cyclin D1 (p=0.04; p=0.015, respectively) and p53 expressions (p=0.02; p=0.04, respectively). Finally, TIMP-1 but no TIMP-2 was associated with the nuclear antigen Ki-67 (p=0.001). These results suggest that TIMP-1 and -2 are expressed in tumoral and stromal tissue in OSCC. TIMP-2 is related to advanced disease, recurrence and poor prognosis.

Expression and clinical significance of matrix metalloproteinase-2 and matrix metalloproteinase-9 in oral squamous cell carcinoma.

To successfully establish a metastasis from an invasive carcinoma, the first step involves the degradation of the underlying basement membrane, which is mainly made up of type IV collagen. Matrix metalloproteinases (MMPs)-2 and -9 are thought to play an important role in its degradation because of their ability to destroy this type of collagen. In order to evaluate the prognostic significance of these proteases, we studied the expression of MMP-2 and -9 in series of 68 OSCC by immunohistochemistry. Of the oral carcinomas, 28% (n = 19) expressed MMP-2, and 17.6% (n = 12) expressed MMP-9. MMP-2 immunoreactivity was significantly higher in patients with alcohol consumption (p = 0.028) (OR = 4), and in those younger than 60 years (p = 0.041). MMP-9 immunostaining showed statistically significant association with the tumor grade of differentiation (p = 0.019), the T-stage (p = 0.05), and also with the alcohol intake (p = 0.04) (OR = 7.67). In the present study, although not statistically significant, we observed that immunoexpression of MMP-2 and MMP-9 was stronger in patients with lymph node metastasis (OR = 1.65 and 2.29, respectively). In patients without regional lymph node metastasis, positive MMP-9 immunostaining was related to poor survival rates (p = 0.02; OR = 5.8). MMP-2 and -9 are involved in the invasion process of oral cancer, and MMP-9 is related to poor prognosis in the subset of patients without neck node metastasis. Ethanol could enhance the carcinogenetic process in oral cavity through its influence in the expression of MMP-2 and -9.