Mario F. Muñoz-Guerra

Characterization of human PA2.26 antigen (T1α-2, podoplanin), a small membrane mucin induced in oral squamous cell carcinomas

We report the full cDNA sequence encoding the human homologue of murine PA2.26 (T1α‐2, podoplanin), a small mucin‐type transmembrane glycoprotein originally identified as a cell‐surface antigen induced in keratinocytes during mouse skin carcinogenesis. The human PA2.26 gene is expressed as 2 transcripts of 0.9 and 2.7 kb in several normal tissues, such as the placenta, skeletal muscle, heart and lung. Using a specific polyclonal antibody raised against a synthetic peptide of the protein ectodomain, PA2.26 was immunohistochemically detected in about 25% (15/61) of human early oral squamous cell carcinomas. PA2.26 distribution in the tumours was heterogeneous and often restricted to the invasive front. Double immunofluorescence and confocal microscopy analysis showed that PA2.26 colocalized with the membrane cytoskeleton linker ezrin at the surface of tumour cells and that its presence in vivo was associated with downregulation of membrane E‐cadherin protein expression. Ectopic expression of human PA2.26 in HeLa carcinoma cells and immortalized HaCaT keratinocytes promoted a redistribution of ezrin to the cell edges, the formation of cell‐surface protrusions and reduced Ca2+‐dependent cell‐cell adhesiveness. These results point to PA2.26 as a novel biomarker for oral squamous cell carcinomas that might be involved in migration/invasion.

Elective neck dissection in early-stage oral squamous cell carcinoma—does it influence recurrence and survival?

This study investigates the influence on survival and regional control rates of neck dissection therapy at the time of surgery of the primary tumor in early stages of squamous cell carcinoma (SCC) of the oral cavity.

Vascularized free fibular flap for the reconstruction of mandibular defects: clinical experience in 42 cases

OBJECTIVE Since the advent of modern microvascular techniques, the fibula has become a reliable method for the reconstruction of partial or total mandibular defects. The purpose of this study is to evaluate our experience with the use of the vascularized free fibular flap for the reconstruction of mandibular defects following surgical resection. PATIENTS AND METHODS During a 5-year period, 102 consecutive patients were treated in our department for reconstruction of oral and maxillofacial defects, using microvascularized free flaps. Forty-two patients were reconstructed by means of the free vascularized fibular flap with or without a skin paddle. Patients underwent resection for benign (n = 15) and malignant (n = 27) entities. Fourteen patients received preoperative radiotherapy and only 1 patient received preoperative chemotherapy. The donor site was closed primarily in 7 cases, whereas an abdominal full-thickness skin graft was used in 35 cases. RESULTS Thirty-eight patients were treated by means of an osteocutaneous flap, whereas only 4 developed an osseous flap. Five patients developed complications related to the vascular anastomosis and needed a second surgical look. One patient died in the immediate postoperative period. The skin island flap was completely viable in 37 cases (88%). Considering bone survival as the main objective, an overall flap survival rate of 92.85% was achieved in the whole series. Endosseous dental implants were placed in 11 patients with adequate outcome. In 5 of these cases the double-barrel technique was performed. CONCLUSION Our results reveal that the vascularized free fibular flap is a reliable method for reconstructing mandibular defects with an acceptable low morbidity rate. The use of the osteocutaneous flap provides good reconstruction of composite mandibular defects. It constitutes an adequate support for dental implants.

Prognostic significance of intratumoral lymphangiogenesis in squamous cell carcinoma of the oral cavity

Clinicopathologic data demonstrated that the lymphatic system is the main route for solid tumor metastasis. However, the effect of intratumoral lymphangiogenesis (IL) on prognosis in oral carcinoma is still unknown because, until recently, no reliable markers for lymphatic endothelium were available. The current study analyzed the lymphatic vessels in tumor tissue specimens of patients with primary oral carcinoma using the new marker, PA2.26.

Osseointegrated Implant Rehabilitation of Irradiated Oral Cancer Patients

PURPOSE The aim of this study is to analyze implant survival in patients who received radiotherapy treatment for oral malignancies and in patients who had suffered mandibular osteoradionecrosis. MATERIALS AND METHODS We reviewed retrospectively 225 implants placed in 30 patients who had received radiotherapy as part of the oncologic treatment. Radiation doses ranged between 50 and 70 Gy. 39 implants were placed after a combined treatment of radiotherapy and chemotherapy. Data referred to tumour type and reconstruction, presence of osteoradionecrosis, region of implant installation and type of prostheses were recorded. Survival rates were calculated with cumulative Kaplan-Meier survival curves and compared between different groups with a log-rank test. RESULTS 152 osseointegrated implants were placed in patients who presented previous reconstruction procedure. Five patients developed osteorradionecrosis as a complication of the radiotherapy treatment. Once osteoradionecrosis had healed in these patients, 41 implants were installed. The overall 5 year survival rate in irradiated patients was 92.6%. Irradiated patients had a marginally significantly higher implant loss than non-irradiated patients. (p = 0.063). The 5 year survival rate in the osteoradionecrosis group was of 48.3% and in the non-osteoradionecrosis group 92.3%, with a statistically significant difference between both groups. (p = 0.002). CONCLUSION Osseointegrated implants enhance oral rehabilitation in most irradiated patients, even being an acceptable option for patients who had suffered osteoradionecrosis. Totally implant supported prostheses are recommended after irradiation providing functional, stable and aesthetically satisfactory rehabilitation.

Contralateral lymph neck node metastasis of squamous cell carcinoma of the oral cavity: a retrospective analytic study in 315 patients.

PURPOSE In relation to primary squamous cell carcinoma (SCC) of the oral cavity, many clinical and histopathologic factors have been reported to be predictive for lymph neck node relapse. However, few large studies concerning the association between clinical-histopathologic features and the development of contralateral lymph neck node relapse (CLNR) after surgical resection of primary SCC of the oral cavity are available. The purpose of this study was to analyze those factors related to the appearance of contralateral lymph neck node relapse in patients with SCC of the oral cavity primarily treated by means of surgery. PATIENTS AND METHODS This study was based on a series of 315 consecutive patients with primary SCC of the oral cavity treated between June 1979 and December 1999. All patients were treated primarily by means of surgery with or without adjuvant radiotherapy. The following data were analyzed for each patient: age, gender, habits, time to diagnosis, performance status, tumor clinical features, histologic grade, TNM staging, type of neck dissection, survival outcome, and functional/esthetic results at the end of the follow-up period. Histologic study included the pTNM classification, tumor size, surgical margins, extracapsular spread of lymph neck node metastasis, perineural infiltration, peritumoral inflammation, and bone involvement. RESULTS Eighty-three patients eventually died of the disease (26.34%). A total of 177 patients were alive with no evidence of recurrence at the end of the study. The mean disease-specific survival rate was 147 +/- 6 months. Twenty-nine (9.1%) patients developed ipsilateral lymph neck node relapse (ILNR), whereas 18 (5.69%) patients developed CLNR. The mean period of time from surgery to the appearance of CLNR was 12.52 months (range, 3 to 49 months). Eighteen of 29 patients with ILNR finally died of the disease. Seven of 18 patients with CLNR died of the disease. Several clinical-pathologic features were predictive for CLNR in SCC of the oral cavity, such as the time to diagnosis, TNM staging, positive ipsilateral clinical N status, histopathologic differentiation, surgical margins of primary tumor resection, type of neck dissection, and perineural infiltration. CONCLUSION Delay in diagnosis 12 or more months is associated with increased CLNR. Clinical and pathologic factors predictive for CLNR are TNM tumor staging IV, histopathologic poor-differentiation of the primary tumor, surgical margins less than 1 cm around the primary tumor, performance of isolated ipsilateral modified type III radical neck dissection, and perineural tumor involvement. Presence of ipsilateral neck metastasis at the time of diagnosis is associated with an augmented incidence of CLNR in SCC of the oral cavity.

Prognostic Factors Influencing Contralateral Neck Lymph Node Metastases in Oral and Oropharyngeal Carcinoma

PURPOSE The prognostic influence of different clinicopathologic factors in contralateral lymph node metastases of oral and oropharyngeal squamous cell carcinoma (SCC) has been rarely described in the literature. Prediction of these contralateral metastases may be of relevance because this factor is strongly associated with poor prognosis. This study analyzed the relationship between predictor factors and the development of contralateral metastases in oral and oropharyngeal SCC. MATERIALS AND METHODS A series of 402 cases of oral and oropharyngeal SCC were analyzed retrospectively. Unilateral neck dissection was carried out in 190 patients, bilateral neck dissection in 101, and tumor resection without neck dissection in 111. The log-rank test was used for survival analysis of contralateral metastases. Correlation between different clinicopathologic factors and the presence of contralateral metastases was studied with the chi(2) test for univariate analysis and logistic regression for association of these factors and contralateral metastases in the multivariate analysis (P < .05). RESULTS Of the patients, 20 (5.1%) had primary positive contralateral metastases in neck dissection specimens and 19 (4.8%) had contralateral recurrences at follow-up. When the 2 groups were taken into consideration, the rate of contralateral metastases of the series was 9%. Gender, tumor location, homolateral positive nodes, tumor extension across the midline, histologic grade, margin status, pattern of growth, and perineural spread were correlated with contralateral metastases in the univariate analysis (P < .05). However, homolateral lymph node metastases and extension across the midline were the most important predictors of contralateral metastases (P < .01) on multivariate logistic regression analysis. Positive contralateral metastases showed a strong correlation with a poor prognosis for survival in this study (P < .05). CONCLUSION Oral and oropharyngeal carcinomas with homolateral positive lymph nodes and tumor extension across the midline are at higher risk of contralateral lymph node involvement. Prediction of contralateral metastases may be useful in planning more aggressive therapies in patients with head and neck SCC with poor prognostic criteria.

Prognostic significance of intratumoral lymphangiogenesis in squamous cell carcinoma of the oral cavity. A study of the early stages

Clinicopathologic data demonstrated that the lymphatic system is the main route for solid tumor metastasis. However, the effect of intratumoral lymphangiogenesis (IL) on prognosis in oral carcinoma is still unknown because, until recently, no reliable markers for lymphatic endothelium were available. The current study analyzed the lymphatic vessels in tumor tissue specimens of patients with primary oral carcinoma using the new marker, PA2.26.

P-cadherin expression reduced in squamous cell carcinoma of the oral cavity: An indicator of poor prognosis

The loss of cadherin expression has been shown to correlate to the invasion and metastasis of many types of carcinomas. The purpose of the current study was to evaluate whether the impaired expression of E‐cadherin (E‐cad) and P‐cadherin (P‐cad) correlated with the clinical evolution and prognosis of oral squamous cell carcinoma (OSCC).

Le Fort I osteotomy, bilateral sinus lift, and inlay bone-grafting for reconstruction in the severely atrophic maxilla: a new vision of the sandwich technique, using bone scrapers and piezosurgery.

Severe atrophy of the edentulous maxilla and progressive pneumatisation of the maxillary sinus can compromise the insertion of dental implants. In this context, ideal implant positioning is limited by inadequate height, width, and quality of the bone. Le Fort I osteotomy and interpositional bone graft is an excellent treatment concept for the dental rehabilitation of patients with atrophied maxilla and reversed intermaxillary relationship. In this report, we indicate the transcendent aspect of elevation and preservation of maxillary sinus and nasal mucosa, modifying the sandwich technique by the useful of bone scrapers and piezosurgery. The procedure is described including a 1-stage approach using cortico-cancellous bone blocks through which implants are placed. In the extremely atrophied alveolar process of the maxilla, this technique provides the desired gain of bone, allows for the ideal placement of dental implants, and improves any discrepancy between the upper and lower arches.