Polymorphous Low-Grade Adenocarcinoma: A Proposed Reconstruction Protocol Based on Past Surgical Experience.

BACKGROUND: To propose a reconstructive protocol based on surgical management experience of polymorphous low-grade adenocarcinoma (PLGA) and the location of the primary lesion. METHODS: Data on the surgical management and the reconstructive technique of 14 histologically conformed patients with PLGA, all treated by the same surgeon, were analyzed and evaluated. RESULTS: Mean follow-up period in our series was 6.2 years. Mean age at diagnosis was 55.5 years and female to male ratio was 2.2:1. The most common presenting sign was a nonpainful lump or mass in an intraoral location. Most patients were managed by wide local excision and reconstruction method varied from primary closure to the use of radial forearm graft. Recurrence appeared in one of the patients in this series, while 2 required further radiation therapy. A protocol for reconstruction of intraoral patients with PLGA is suggested based on our analysis. CONCLUSION: Surgical management is the gold standard for PLGA treatment. Neck dissection is recommended only in patients with presurgery fine-needle aspiration confirmed lymph node involvement. The reconstruction depends mainly on location and size of the primary lesion.

The Possible Role of Human Papillomavirus Infection in the prognosis of Oral Squamous Cell Carcinoma in a Northern Israel Population.

BACKGROUND: Several types of human papillomavirus (HPV) have been found to be associated with oral squamous cell carcinoma (OSCC). Still, the significance of HPV infection and its relationship to patient prognosis remains an important matter of debate. OBJECTIVES: To investigate the incidence of HPV infection in OSCC patients in northern Israel populations to determine its role in the etiology and prognosis of OSCC. METHODS: OSCC tissues were gathered from the pathology departments at Rambam and Padeh medical centers in northern Israel. HPV DNA typing and immunohistochemistry for p16INK4A antibodies were conducted to evaluate their incidence in OSCC tissues. Statistical analysis regarding its expression in the different sub-populations (Jews, Arabs, Druze) was conducted using chi-square and Fisher's exact tests. RESULTS: The study included 82 patients: 53 men and 29 woman; median age 62.1 years; 54 Jews, 25 Arabs, and 3 Druze. The overall incidence of HPV expression was 45% (n=37). The median age of HPV-positive patients was 53 years vs. 65.8 in the negative group (P < 0.001). The 5 year overall survival of HPV-positive patients was not significantly higher than HPV-negative patients. A significant association was found between P16 expression and overall survival (log-rank P = 0.001). CONCLUSIONS: HPV infection in OSCC was not found to be significant in this study; however, P16 expression in the tumor tissue was found to be a positive prognostic factor for better survival.

Clinical significance of preoperative imaging in oral squamous cell carcinoma compared with lymph node status: a comparative retrospective study.

OBJECTIVE: The accuracy and sensitivity of commonly used imaging modalities in evaluating oral cavity cancer was evaluated by comparing the preoperative radiologic findings and the postoperative pathology report. STUDY DESIGN: Patients with oral squamous cell carcinoma, who had undergone at least 1 imaging test 2 weeks before surgery were included. Radiologic findings were compared with the dissected neck findings to assess the lymph node status. Sensitivity and specificity of the imaging modalities were calculated by using the χ2 test. RESULTS: Sensitivities for detecting metastatic neck lymph nodes at a threshold of 1 cm were 48% (P = .02) and 43.8% (P = .3) for computed tomography (CT) and magnetic resonance imaging respectively. Specificities were 76.3% and 70%, respectively. As for the 1.5 cm threshold, sensitivities were 36% (P = .002) and 31.3% (P = .5), respectively, and specificities were 91.5% and 76.7%, respectively. PET-CT was the most sensitive modality in the present study, with a P value of .02. CONCLUSIONS: The different studied imaging modalities used for preoperative neck staging are not sensitive enough and would lead to underdiagnoses of a significant proportion of patients. Thus, prophylactic neck dissection for occult neck disease is of extreme importance and remains the gold standard for oral cancer treatment.

Indications for Elective Tracheostomy in Reconstructive Surgery in Patients With Oral Cancer.

BACKGROUND: Oral cancer surgery carries a high risk of upper airway obstruction; yet optimal airway management approach remains controversial. AIM OF STUDY: The purpose of the present study was to evaluate the use of tracheostomy in oncological patients undergoing oral cancer surgery with intra oral flap reconstruction. METHODS: The study cohort included 75 patients with oral cancer, who underwent major intraoral resections and reconstruction with vascularized flaps. RESULTS: Thirty-six percent of the patients received elective tracheostomy (27 patients). Mean hospital stay of the patients with tracheostomy was 28.4 ±â€Š12.5 days compared with 9.7 ±â€Š2.1 days in the nontracheostomy patients. A scoring system rendered from this study suggests that patients with a total scoring at or above 8 should be considered for elective tracheostomy. CONCLUSIONS: With appropriate postoperative monitoring, selected patients can be managed without routine elective tracheostomy, yet, patients with comorbidities, mostly elderly patients, which undergo surgical resection and reconstruction in high-risk areas that can result in a bulky flap that pose danger to the postoperative airway, should receive elective tracheostomy.

Functional Reconstruction in Mandibular Avulsion Injuries.

The present report describes the planning and surgery as well as pitfalls and management of a patient with a near total mandibular avulsion injury that was rehabilitated using three-dimensional (3D) laser printing of a titanium lower jaw. Laser-sintering involves zapping layers of powdered metal to recreate a 3D implantable skeletal defect. The process involves using either mirror imaging of the unaffected side or using archival image database of healthy individuals. A 25-year-old man presented with a gunshot injury that left him with a near total avulsed mandible. The patient received state-of-the-art treatment using a laser 3D printed mandible which was connected to the muscles of mastication for functionality. The inner side of the titanium jaw was filled with the patient's comminuted fractured bones in addition to harvested iliac crest bone graft that was covered with the patient's remaining periosteal tissue. The implantation of a near total mandible using 3D laser printing is a fast and predictable process that in selected patients can result in aesthetically as well as functionally excellent results. The authors believe that the future of craniofacial reconstruction will employ these methods for facial bony reconstruction.

Airway Management of the Patient with Maxillofacial Trauma: Review of the Literature and Suggested Clinical Approach.

According to the Advanced Trauma Life Support recommendations for managing patients with life-threatening injuries, securing the airway is the first task of a primary caregiver. Airway management of patients with maxillofacial trauma is complex and crucial because it can dictate a patient's survival. Securing the airway of patients with maxillofacial trauma is often extremely difficult because the trauma involves the patient's airway and their breathing is compromised. In these patients, mask ventilation and endotracheal intubation are anticipated to be difficult. Additionally, some of these patients may not yet have been cleared of a cervical spine injury, and all are regarded as having a full stomach and having an increased risk of regurgitation and pulmonary aspiration. The requirements of the intended maxillofacial operation may often preclude the use of an oral intubation tube, and alternative methods for securing the airway should be considered before the start of the surgery. In order to improve the clinical outcome of patients with maxillofacial trauma, cooperation between maxillofacial surgeons, anesthesiologists, and trauma specialists is needed. In this review, we discuss the complexity and difficulties of securing the airway of patients with maxillofacial trauma and present our approach for airway management of such patients.

The Molecular and Cellular Events That Take Place during Craniofacial Distraction Osteogenesis.

SUMMARY: Gradual bone lengthening using distraction osteogenesis principles is the gold standard for the treatment of hypoplastic facial bones. However, the long treatment time is a major disadvantage of the lengthening procedures. The aim of this study is to review the current literature and summarize the cellular and molecular events occurring during membranous craniofacial distraction osteogenesis. Mechanical stimulation by distraction induces biological responses of skeletal regeneration that is accomplished by a cascade of biological processes that may include differentiation of pluripotential tissue, angiogenesis, osteogenesis, mineralization, and remodeling. There are complex interactions between bone-forming osteoblasts and other cells present within the bone microenvironment, particularly vascular endothelial cells that may be pivotal members of a complex interactive communication network in bone. Studies have implicated number of cytokines that are intimately involved in the regulation of bone synthesis and turnover. The gene regulation of numerous cytokines (transforming growth factor-ß, bone morphogenetic proteins, insulin-like growth factor-1, and fibroblast growth factor-2) and extracellular matrix proteins (osteonectin, osteopontin) during distraction osteogenesis has been best characterized and discussed. Understanding the biomolecular mechanisms that mediate membranous distraction osteogenesis may guide the development of targeted strategies designed to improve distraction osteogenesis and accelerate bone regeneration that may lead to shorten the treatment duration.

Heparanase, a potential marker for premalignant oral cavity cancer.

BACKGROUND/AIM: In the past we have shown that the heparanase gene expression significantly correlates to oral cancer patient survival. Our aim was to study heparanase expression in all stages of carcinogenesis. MATERIALS AND METHODS: Heparanase expression (mRNA and protein), as well as its enzymatic activity were studied separately in the nucleus and cytoplasm of both normal and cancerous cells using an in vivo oral cancer mouse model. RESULTS: Heparanase nuclear expression was associated with normal tissue; at the time carcinogenesis is initiated heparanase translocates to the cytoplasm and increases protein expression and enzymatic activity, as the cancer progresses. Heparanase overall expression is increased in cancer formation from premalignant to invasive squamous cell carcinoma (SCC). CONCLUSION: Heparanase is suggested to be a prognostic and diagnostic marker for oral premalignant lesions which could have a major impact on future prognosis and diagnosis of SCC of the oral cavity.

Lymphoepithelial carcinoma--review of the treatment modalities and report of a rare case in the sublingual gland.

Controversies exist in the current literature regarding the treatment of lymphoepithelial carcinoma (LEC). The presented study summaries the literature controversies in the treatment of LEC and present a case of a rare LEC diagnosed in the sublingual gland of an otherwise healthy 21-year-old Arab woman. The patient was admitted for swelling in the sublingual area. A biopsy indicated a diagnosis of LEC of the sublingual gland. Treatment included a wide resection with safe margins, marginal mandibulectomy, functional neck dissection, and a radial forearm free flap for reconstruction. The patient received concomitant radiotherapy and has remained disease free since her last follow-up. The recommended primary treatment, based on the literature review, is primary surgical excision with neck dissection and optional adjuvant radiotherapy to the gland area. Chemotherapy was not found to be beneficial according to the literature.

Does long-term treatment with Doxil® predispose patients to oral cancer?

We present a possible adverse reaction related to long-term use of Doxil(®) in female patients. We believe that long-term use of Doxil(®) may predispose female patients to oral squamous cell carcinoma. The patients in this report were not exposed to the common risk factors related to oral cancer formation such as smoking or alcohol consumption. Both patients were 59-year-old females. The first patient was diagnosed in 2001 with stage IIIC ovarian cancer. Seven years following treatment with Doxil(®), she was diagnosed with stage III squamous cell carcinoma of the right maxilla. The second patient was diagnosed with Kaposi's sarcoma with evidence of spread to the lungs. Four years following treatment with Doxil(®) she was diagnosed with stage I squamous cell carcinoma of the left maxilla. A literature review did not reveal any report on Doxil(®) and predisposition to oral cancer; however, we found an abstract that was presented at the last annual meeting of the American Society of Clinical Oncology (ASCO) by Cannon et al. When we combine the data from Cannon et al. and the data presented here, a total of six female patients developed an epithelial carcinoma of the oral cavity following long-term treatment with Doxil(®). We believe that a large-scale study should be initiated on patients that were treated with Doxil(®) for more than 3 years, since these patients might be at risk for developing secondary cancer of the oral cavity.

Treatment protocol for high velocity/high energy gunshot injuries to the face.

Major causes of facial combat injuries include blasts, high-velocity/high-energy missiles, and low-velocity missiles. High-velocity bullets fired from assault rifles encompass special ballistic properties, creating a transient cavitation space with a small entrance wound and a much larger exit wound. There is no dispute regarding the fact that primary emergency treatment of ballistic injuries to the face commences in accordance with the current advanced trauma life support (ATLS) recommendations; the main areas in which disputes do exist concern the question of the timing, sequence, and modes of surgical treatment. The aim of the present study is to present the treatment outcome of high-velocity/high-energy gunshot injuries to the face, using a protocol based on the experience of a single level I trauma center. A group of 23 injured combat soldiers who sustained bullet and shrapnel injuries to the maxillofacial region during a 3-week regional military conflict were evaluated in this study. Nine patients met the inclusion criteria (high-velocity/high-energy injuries) and were included in the study. According to our protocol, upon arrival patients underwent endotracheal intubation and were hemodynamically stabilized in the shock-trauma unit and underwent total-body computed tomography with 3-D reconstruction of the head and neck and computed tomography angiography. All patients underwent maxillofacial surgery upon the day of arrival according to the protocol we present. In view of our treatment outcomes, results, and low complication rates, we conclude that strict adherence to a well-founded and structured treatment protocol based on clinical experience is mandatory in providing efficient, appropriate, and successful treatment to a relatively large group of patients who sustain various degrees of maxillofacial injuries during a short period of time.

Incidence of oral cancer occult metastasis and survival of T1-T2N0 oral cancer patients.

PURPOSE: In head and neck cancer, the most important prognostic factor is the presence or absence of neck metastasis. Although still debated in the published data regarding the "wait and see" policy for Stage T1-T2 oral cancer, a large number of clinicians support the necessity of neck dissection, especially in cases of oral tongue carcinoma, because of the poor prognosis and high risk of recurrence. The aim of the present study was to summarize and quantify the incidence of occult metastasis in oral cancer treatment at the oral and maxillofacial surgery department, Rambam Medical Center, in the past 10 years. PATIENTS AND METHODS: A total of 142 neck dissections performed at our department in the past 10 years (1998 to 2009) and a series of 68 patients (44 men and 22 women) treated for Stage T1N0 or T2N0 oral cancer were included in the present retrospective study. All patients underwent surgical resection of the oral cancer and selective neck dissection of the ipsilateral side. RESULTS: Occult lymph node metastases were detected in 11 patients (16% overall, 9 in the tongue, 1 in the buccal mucosa, and 1 in the gingiva of the mandible). The frequency of occult metastasis from tongue carcinoma was 34% (9 of 26 cases). The 5-year survival rate in the present study was 78.9%. In patients who underwent chemotherapy, radiotherapy, brachytherapy, or a combination of the 3 after surgical management, the overall survival rate decreased significantly to 22.5% (P = .006, log-rank test). CONCLUSION: The incidence of occult metastasis in patients with oral cancer in the present study was 16% overall. In those with tongue carcinoma, a much greater incidence (34%) of occult metastasis was detected. Furthermore, the need for chemoradiotherapy after initial surgical management, mainly because of occult metastasis, was a significant negative predictor of patient outcome. The results of the present study emphasize the need for prophylactic neck dissection in patients with oral cancer diagnosed with Stage T1N0 or T2N0 disease, especially when the primary lesion is localized in the tongue.

Polymorphous low grade adenocarcinoma: case series and review of surgical management.

PURPOSE: The aim of the present study was to review the published data regarding the management of polymorphous low-grade adenocarcinoma (PLGA) and present our experience in the treatment of patients diagnosed with PLGA. MATERIALS AND METHODS: We performed a review of the published data of the treatment possibilities for PLGA, and report on a case series of 4 patients diagnosed with palatal PLGA. RESULTS: The mean age at diagnosis was 61.75 years. All cases were localized on the hard palate. The male/female ratio was 1:3. One patient had an ulcerative painful lump. In correlation with the published data, most of our patients presented initially with a diagnosis that was not conclusive for the presence of PLGA. The most common initial diagnostic findings were adenoid cystic carcinoma and pleomorphic adenoma. The treatment of choice was surgical excision of the tumor with safe margins of 1.5 cm. One patient had a positive cervical lymph node metastasis and underwent an elective neck dissection followed by radiotherapy. Local recurrence was diagnosed in 1 patient 6 years after the surgical management. Most cases were reconstructed using an obturator, except for 1 patient who underwent reconstruction using the temporalis myofascial flap. CONCLUSIONS: PLGA is a slow-growing, distinct, uncommon neoplasm of the minor salivary glands. Because it is characterized by a diverse morphologic pattern that resembles adenoid cystic carcinoma or pleomorphic adenoma, the initial diagnosis is usually inconclusive. Until a final diagnosis has been made, we believe that the reconstruction possibilities should be mainly obturators to allow a good visualization of the surgical site. The use of microvascular free flaps or rotational flaps should be reserved to patients with clearer pathologic diagnosis.

Prognostic value of heparanase expression and cellular localization in oral cancer.

BACKGROUND: Metastases formation depends on the ability of tumor cells to invade basement membranes in a process involving enzymes capable of degrading extracellular matrix components. METHODS: We examined the expression of heparanase in oral carcinomas and correlated its staining extent, intensity, and cellular localization with patients' outcome. RESULTS: Quantitative real-time polymerase chain reaction (PCR) revealed over 4-fold increase in heparanase levels in oral carcinomas compared to adjacent normal tissue. Normal oral epithelium was found negative for heparanase, while all oral carcinomas stained positively for heparanase. Heparanase staining was associated with Ki67 staining, a measure of cell proliferation. Notably, whereas cytoplasmic localization of heparanase was associated with high-grade carcinomas, nuclear localization of the enzyme was found primarily in low-grade, well-differentiated tumors, and in all oral verrucous carcinomas. CONCLUSION: Expression level and cellular localization of heparanase could serve as an important diagnostic marker in patients with oral cancer.

The induction of tuftelin expression in PC12 cell line during hypoxia and NGF-induced differentiation.

The tuftelin protein isoforms undergo post-translation modifications, and are ubiquitously expressed in various tissues in embryos, adults, and tumors. Developmental and pathological studies suggested an apparent correlation between oxygen deprivation and tuftelin expression. The aim of the study was therefore to investigate the effect of a pathological insult (hypoxia) and a physiological growth factor (NGF), which antagonistically regulate HIF1 expression, on tuftelin expression using the neuronal PC12 cell model. In the present study, we first demonstrated the expression of tuftelin in PC12 cells, providing an experimental system to investigate the pathophysiological role of tuftelin. Furthermore, we demonstrated the induction of tuftelin during hypoxia by oxygen deprivation and during chemical hypoxia by cobalt chloride. Down-regulation of HIF1α mRNA blocked hypoxia-induced HIF1α expression, and reduced by 89% hypoxia-induced tuftelin expression. In mice, intraperitoneal injection of cobalt chloride significantly induced tuftelin mRNA and protein expression in the brain. During NGF-mediated PC12 differentiation, tuftelin expression was significantly induced in correlation with neurite outgrowth. This induction was partially blocked by K252a, a selective antagonist of the NGF receptor TrkA, indicating the involvement of the TrkA-signaling pathways in tuftelin induction by NGF. Revealing the physiological role of tuftelin will clarify mechanisms related to the "hypoxic genome," and NGF-induced neurotrophic and angiogenic effects.

Surgical approach to impacted mandibular third molars--operative classification.

PURPOSE: The aim of the present study is to suggest a convenient way to classify the position of the impacted third mandibular molar relative to the mandibular canal and to suggest indications for the use of each surgical approach for mandibular third molar extraction. MATERIALS AND METHODS: The presented new typing system, Third Molar Classification (TMC), is a simple and easy-to-apply method for the surgical management of mandibular third molars and can be extended for any ectopic or impacted mandibular tooth. There are 3 major types of third molar positions. The second type is subdivided further into 2 subtypes. In the present study, 9 patients with high-risk mandibular third molars were treated according to the present classification and are presented and discussed. Patients typed as TMC IIb were treated with a sagittal split osteotomy approach and patients typed as TMC III were treated with an extraoral approach. RESULTS: The operative classification was successfully implemented in very rare cases of deeply impacted mandibular third molars. In 3 of 9 cases (33%) minor complications included some degree of hypoesthesia using the extraoral approach; these complications resolved spontaneously without the need for any intervention. CONCLUSIONS: The present study describes the use of a new surgical classification system for treatment planning in all types of mandibular third molar extractions. We believe that the present classification could help the oral and maxillofacial surgeon in decision-making and limit the possible risks that are present when attempting to extract impacted mandibular third molars.

The use of the temporalis myofascial flap in oral cancer patients.

PURPOSE: The purpose of this article is to present our experience using the simple, reliable, and predictable temporalis myofascial flap (TMF) in rehabilitation and reconstructive surgery in cancer patients who are older and whose health is compromised in a way that precludes the use of microvascular free flaps. PATIENTS AND METHODS: Our series includes 10 patients (8 men and 2 women), ranging in age from 62 to 85 years (mean, 73.4 years). A full-thickness anteroinferiorly based TMF was used in 5 patients for palatal reconstruction, 3 patients for buccal lining reconstruction, and 2 patients for reconstruction after resection of facial skin and buccal mucosa. RESULTS: The TMF survival rate in this study was excellent, with an 80% success rate (2 minor complications). Complications included 1 case of a partial distally necrotic flap that resolved after local debridement and did not require further flap manipulation and 1 case of transient, spontaneously resolved facial nerve (temporal branch) palsy and limited mouth opening (<20 mm), which also resolved after judicious physiotherapy. CONCLUSIONS: The TMF was found in this study to have a fairly low complication rate, was relatively easy to use, and had a predictable outcome. The proximity and reliability of the myofascial flap make it a favorable and highly recommended candidate for oral and maxillofacial reconstructive surgery in elderly patients, who usually have relatively poor recovery potential and decreased physiologic reserves.

Regeneration of bone and periodontal ligament induced by recombinant amelogenin after periodontitis.

Regeneration of mineralized tissues affected by chronic diseases comprises a major scientific and clinical challenge. Periodontitis, one such prevalent disease, involves destruction of the tooth-supporting tissues, alveolar bone, periodontal-ligament and cementum, often leading to tooth loss. In 1997, it became clear that, in addition to their function in enamel formation, the hydrophobic ectodermal enamel matrix proteins (EMPs) play a role in the regeneration of these periodontal tissues. The epithelial EMPs are a heterogeneous mixture of polypeptides encoded by several genes. It was not clear, however, which of these many EMPs induces the regeneration and what mechanisms are involved. Here we show that a single recombinant human amelogenin protein (rHAM(+)), induced in vivo regeneration of all tooth-supporting tissues after creation of experimental periodontitis in a dog model. To further understand the regeneration process, amelogenin expression was detected in normal and regenerating cells of the alveolar bone (osteocytes, osteoblasts and osteoclasts), periodontal ligament, cementum and in bone marrow stromal cells. Amelogenin expression was highest in areas of high bone turnover and activity. Further studies showed that during the first 2 weeks after application, rHAM(+) induced, directly or indirectly, significant recruitment of mesenchymal progenitor cells, which later differentiated to form the regenerated periodontal tissues. The ability of a single protein to bring about regeneration of all periodontal tissues, in the correct spatio-temporal order, through recruitment of mesenchymal progenitor cells, could pave the way for development of new therapeutic devices for treatment of periodontal, bone and ligament diseases based on rHAM(+).