Pedicled buccal flaps as a backup procedure for intraoral reconstruction.

BACKGROUND: Intraoral soft tissue deficiency and impaired wound beds are common problems after cleft and tumour surgery or after dental trauma. Frequently, limited defects are overtreated with extensive microvascular reconstruction procedures, but pedicled flaps remain useful, as they are simple to harvest, and they provide a reliable outcome. The buccal flap, first described in the 1970s, has been used for palatine lengthening in cleft patients over decades. In the following, we present an expanded indication in cases of palatal fistula, complex vestibulum, exposed bone in orthognathic surgery, and osteoradionecrosis. METHODS: We conducted a retrospective chart review and report on all buccal flaps harvested in our department within the last 3 years with a follow-up period of at least half a year after flap surgery. Patients of all age groups and treatment indications in which a buccal flap was used were implicated in the evaluation. RESULTS: Sixteen buccal flaps were performed in 10 patients. The median age at the time of surgery was 42 years, reaching from 12 up to 66 years. Fourteen buccal flaps were used for upper jaw or palatal coverage; two buccal flaps were used in the mandible. In terms of complications (four flaps; 25%), there were two partial flap failures, one wound dehiscence and one wound dehiscence. There were no failures of the remaining mucosal flap islands after pedicle dissection. CONCLUSION: The buccal flap is a reliable and straightforward approach to challenging intraoral wound beds with soft tissue deficiency. We thoroughly discuss the additional indications for buccal flap surgery, describe the harvest technique, and provide strategies to prevent intra- and postoperative complications.

Macrophage and T-Cell Infiltration and Topographic Immune Cell Distribution in Non-Melanoma Skin Cancer of the Head and Neck.

Non-melanoma skin cancer (NMSC) is a heterogeneous tumor entity that is vastly determined by age and UV-light exposure leading to a great mutational burden in cancer cells. However, the success of immune checkpoint blockade in advanced NMSC and the incidence and disease control rates of NMSC in organ transplant recipients compared to immunologically uncompromised patients point toward the emerging importance of the immunologic activity of NMSC. To gain first insight into the role of T-cell and macrophage infiltration in NMSC of the head and neck and capture their different immunogenic profiles, which appear to be highly relevant for the response to immunotherapy, we conducted a whole slide analysis of 107 basal cell carcinoma (BCC) samples and 117 cutaneous squamous cell carcinoma (cSCC) samples. The CD8+ and CD68+ immune cell expression in both cancer types was evaluated by immunohistochemistry and a topographic distribution profile, and the proportion of both cell populations within the two tumor entities was assessed. The results show highly significant differences in terms of CD8+ T-cell and CD68+ macrophage infiltration in BCC and cSCC and indicate cSCC as a highly immunogenic tumor. Yet, BCC presents less immune cell infiltration; the relation between the immune cells compared to cSCC does not show any significant difference. These findings help explain disparities in local aggressiveness, distant metastasis, and eligibility for immune checkpoint blockade in both tumor entities and encourage further research.

Preoperative Peroneal Artery Perforator Mapping Using Indocyanine Green Angiography: A Prospective Clinical Trial.

BACKGROUND: Perforator imaging is a prerequisite in preoperative planning of the peroneal perforator flap and the fibula skin island. Although reports indicate that indocyanine green angiography assessment method might be advantageous over conventional ultrasound-based techniques (i.e., Doppler and color duplex), in practice, clear evidence is lacking. Thus, a comparative assessment of the utility of indocyanine green angiography and ultrasound-based techniques in the identification of suitable lower leg skin perforators was performed. METHODS: A prospective clinical cohort study with a series of 12 consecutive patients was conducted to assess indocyanine green angiography, Doppler ultrasound, and color duplex ultrasound techniques for preoperative perforator detection in the lower leg before free fibula flap harvest. Anatomical dissection served as a reference. Parameters measured were perforator spatial distance to the reference (precision), operative time expenditure, and ease of device usage for assessment/outcomes. RESULTS: This study included 12 patients, with a total of 27 perforators. Exhibition of technique sensitivity and positive predictive values were as follows: indocyanine green angiography, 93 percent and 100 percent; Doppler ultrasound, 82 percent and 82 percent; and color duplex ultrasound, 89 percent and 86 percent, respectively. With regard to the indocyanine green angiography technique, the distance to the actual perforator location was significantly shorter, which aided detection and lesser time expenditure during operation. CONCLUSIONS: The indocyanine green angiography technique proved to have high precision, sensitivity, positive predictive value, and easy-to-use capabilities because of its exceptional spatial and temporal information, compared to the conventional, ultrasound-based techniques. Therefore, indocyanine green angiography is superior for preoperative perforator imaging of the lateral lower leg. CLINICAL QUESTION/LEVEL OF EVIDENCE: Diagnostic, II.

Neoadjuvant Immunotherapy of Oral Squamous Cell Carcinoma: Case Report and Assessment of Histological Response.

BACKGROUND: The treatment of oral cancer remains challenging due to its infiltrative nature and a high tendency for tumour relapse leading to an overall poor prognosis. In the case of early recurrence, the patient's prognosis deteriorates dramatically, with survival rate dropping to below 30%. Minimal improvements in survival trends in recurrent and advanced stage tumours have been reported in recent decades. Neoadjuvant immunotherapy may represent a new therapeutic approach changing the standard of care in advanced oral cancer therapy. CASE PRESENTATION: We describe the case of a woman in her late 30's who presented in mid-2019 with oral squamous cell carcinoma (OSCC) localized to the floor of the mouth. After initial R0 resection, selective neck dissection, and adjuvant brachytherapy, an early recurrence of OSCC located between the hyoid bone and the mandible was diagnosed at the end of 2019. An off-label treatment regimen was performed with neoadjuvant use of Pembrolizumab 19 days prior to salvage surgery. Radiological and histological assessment of T-cell and programmed cell death protein 1 ligand 1 (PD-L1) expression was performed before and after checkpoint inhibitor application. Neoadjuvant immunotherapy resulted in increased T-cell infiltration and PD-L1 expression, as well as a significant tumour necrosis rate. One cycle of Pembrolizumab led to significant regressive tumour changes with increases in immune infiltration, sclerosis, and necrosis of 75% of the tumour mass with only 25% vital tumour cells remaining. By June 2020, the patient remained without recurrence. CONCLUSIONS: The case presented outlines the potential effects of neoadjuvant immunotherapy in recurrent or advanced OSCC prior to definitive surgical tumour treatment. The benefit of additional adjuvant treatment after histologic response will be discussed. The case is also analysed considering ongoing clinical trials of neoadjuvant immunotherapy for head and neck malignancies.

Management of anticoagulated patients in dentoalveolar surgery: a retrospective study comparing bridging with heparin versus unpaused vitamin K antagonist medication.

BACKGROUND: The aim of this study was to investigate the occurrence of postoperative bleeding following dentoalveolar surgery in patients with either continued vitamin K antagonist medication or perioperative bridging using heparin. METHODS: A retrospective study was performed analyzing patients who underwent tooth extraction between 2012 and 2017. Patients were retrospectively allocated into two comparative groups: un-paused vitamin K antagonist medication versus bridging using heparin. A healthy, non-anticoagulated cohort with equivalent surgery served as a control group. Main outcome measures were: the occurrence and frequency of postoperative bleeding, the number of removed teeth, the surgical technique of tooth removal (extraction/osteotomy/combined extraction and osteotomy) and the prothrombin time. RESULTS: In total, 475 patients were included in the study with 170 patients in the group of un-paused vitamin K antagonist medication VG, 135 patients in the Bridging group BG and 170 patients in the control group CG. Postoperative bleeding was significant: CG versus VG p = 0.004; CG versus BG p < 0.001, BG versus VG p < 0.001. A significant correlation of number of the extracted teeth in the BG (p = 0.014) and no significance in VG (p = 0.298) and CG (p = 0.210) and in the BG versus VG and CG with p < 0.001 in terms of surgical intervention extraction. No difference observed in terms of prothrombin time. CONCLUSIONS: Bridging with heparin increases the risk for bleeding compared to un-paused vitamin K antagonist medication. The perioperative management of anticoagulated patients requires a well-coordinated interdisciplinary teamwork to minimize or at best avoid both: postoperative bleeding and thromboembolic incidences.

Thermal Imaging in a Clinically Non-assessable Free Flap Reconstruction of the Face.

Free flap monitoring and early detection of malperfusion are a central aspect in reconstructive surgery. Warm ischemia, measured as the time a certain tissue is able to survive without any additional medical or thermal treatment, ranges from hours in muscle and nerval tissue up to days in bony tissue. Hence, meticulous flap monitoring is essential to discover early signs of malperfusion and decide upon timely re-intervention. Besides clinical examination techniques and Doppler sonography, a multitude of mostly experimental procedures are available to evaluate free flap perfusion. Particularly in older patients, the assessment of the skin island in microvascular grafts is a demanding task because the natural loss of elasticity, the reduction of subcutaneous tissue, and the decrease in water content limit the visibility of capillary filling and favor hematomas. We report a case of a 90-year-old woman with an extensive cutaneous squamous cell carcinoma of the right zygomatic and lateral orbital region without any locoregional or distant metastasis. Due to the resilient health status, we decided for a surgical approach with consecutive microvascular radial forearm flap reconstruction. On account of the difficult assessment of elderly skin after microvascular transplantation, we decided on additional flap monitoring by thermal heat imaging during the operation and aftercare. This case report discusses the successful application of thermal heat imaging in a clinical non-assessable free flap and discusses the application of dynamic infrared thermography as a monitoring tool in microvascular free flap surgery.

Oxidative and Nitrosative Stress in Oral Squamous Cell Carcinoma.

INTRODUCTION: The incidence of oral squamous cell carcinoma (OSCC) shows a constant increase, while the long-term outcome remains poor over the last decades. Radical oxygen and nitrogen species (RONS) - initially released by carcinogens, such as alcohol and tobacco, and later maintained by the tumor microenvironment - appear to be strongly associated to chronic inflammation, tumor induction, progression, and metastatic spread. The aim of this study was to evaluate the role of oxidative and nitrosative stress in primary OSCC compared to healthy tissue specimens and to identify their impact on tumor carcinogenesis. MATERIALS AND METHODS: In this basic research study, tissue samples of 30 patients with primary OSCC were evaluated for the expression of pAKT, pERK, 3-NT, NOS1, NOS3, MAPK1, and IP-8 by immunohistochemistry and RT-PCR and compared to those of a healthy control group (n = 30). RESULTS: The results showed a significantly increased expression of pAKT (p < 0.001), pERK (p = 0.01), 3-NT (p = 0.039), NOS1 (p = 0.025), NOS3 (p = 0.046), and MAPK1 (p = 0.032) in OSCC tissue samples compared to healthy controls. CONCLUSION: The results of this study prove the tested stable degradation products to be suitable for the detection of RONS in OSCC. Moreover, the significantly increased expression underlines the role of RONS in carcinogenesis of OSCC, suggests specific mechanisms of detection, and anticipates supplementary research.

Correction to: Osseous ingrowth in allogeneic bone blocks applied for vertical bone augmentation: a preclinical randomized controlled study.

In the article by Möst et al., entitled "Osseous ingrowth in allogeneic bone blocks applied for vertical bone augmentation: a preclinical randomized controlled study.

Development of a template tool for facilitating fibula osteotomy in reconstruction of mandibular defects by digital analysis of the human mandible.

OBJECTIVES: Mandibular reconstruction after segmental mandibulectomy can be challenging without virtual surgical planning and osteotomy guides. The purpose of this study was to analyze anatomic parameters to facilitate the evaluation of ideal fibula wedge osteotomies to reconstruct the neomandibula in a simple and cost-effective manner without the need for preoperative virtual planning. MATERIALS AND METHODS: Computed tomography scans were acquired from randomly selected patients, and all images were obtained from routine clinical diagnostics, e.g., tumor staging, or preoperatively before reconstruction. Data was used to calculate stereolithographic models of the mandible for length and angle measurements. Statistical analysis was performed (p < 0.05). RESULTS: CT scans of 100 patients were analyzed: 39 were female and 61 were male patients, mean age was 59.08a. The mandibular arch angle proved to be constant with 241.07 ± 2.39°. The outside B-segment length was 80.05 ± 5.16 mm; the anterior S-segment length was 27.69 ± 3.16 mm. The angle of the mandibular arch showed differences in means (p = 0.004) between age groups, but effect was proved low. No relevant statistical significances were detected. CONCLUSIONS: The development of a mandible reconstruction template tool would benefit the majority of head and neck patients, which is due to a constant mandibular arch angle and symphysis segment length throughout the general patient population, allowing the mimicking of a harmonic mandibular arch with up to three fibula segments. CLINICAL RELEVANCE: The developed mandible reconstruction template tool can facilitate the fibula wedge osteotomies necessary for reconstruction of an ideal neomandibula providing a novel approach which is simple and cost-effective.

Osseous ingrowth in allogeneic bone blocks applied for vertical bone augmentation: a preclinical randomised controlled study.

OBJECTIVES: The aim of the present study was the qualitative and quantitative evaluation of osseous graft consolidation using allogeneic bone blocks for vertical bone augmentation in an animal model. MATERIAL AND METHODS: Standardised allogeneic and autologous bone blocks were fixed on the frontal skull of 20 adult female pigs and covered with a resorbable collagen membrane. Animals were sacrificed after 2 and 6 months. Specimens were histologically and histomorphometrically analysed focusing on the amount of vital bone, residual bone substitute material and connective tissue. Furthermore, the amount of expression of bone matrix proteins (collagen type I and osteocalcin) and de novo vessel formation (von Willebrand factor) were quantified by immunohistochemistry. RESULTS: Significantly more allogeneic bone blocks failed for both evaluation time points (p < 0.05). Allogeneic blocks showed significantly less vital bone with more connective tissue formation compared to autologous bone blocks. Increased vessel formation could be detected for both evaluation time points in the contact area of autologous bone with local bone. The expression of collagen type I and osteocalcin was significantly lower in the allogeneic bone graft. CONCLUSIONS: Allogeneic cancellous bone blocks showed a significantly higher failure rate compared to autologous bone blocks. Allogeneic bone blocks seemed to negatively affect bone formation or negatively influence the host in the long term, and increased connective tissue formation and block loss should be anticipated. CLINICAL RELEVANCE: In order to maintain patient safety and treatment success clinicians should be persuaded to make a conscious choice of the applied biomaterials with regard to their components and structure.

Evaluation of neck dissection with frozen section biopsy - Management of levels IV and V.

INTRODUCTION: Neck dissection is an essential component of oral cancer therapy. Based on a standardised approach to cervical lymph node management, we seek to define the relevance of neck dissection extension in cN + cases. MATERIAL AND METHODS: A retrospective analysis from January 2009 to February 2017 identified 84 patients with oral squamous cell carcinoma with a cN + neck or histologically proven lymph node involvement in intraoperative frozen sectioning and who received modified radical neck dissection according to the presented neck dissection algorithm. RESULTS: Overall 11 patients showed lymph node metastasis level IV or V, whereas 19 developed disease recurrence, of which 5 cases were neck recurrences. A total of 30 patients died within the time of observance (overall survival of n = 54). None of those patients with pN + status in levels IV and V reached a 5-year survival. DISCUSSION: With a look to the possibility of a 5-year survival in patients with a N+ status in level IV and V, the justification for a radical approach to the neck appears questionable. However, modified radical neck dissection appears to be a suitable for a high-risk oral cancer subgroup. A randomised controlled trial is needed to define guidelines for the neck dissection extent in c/pN + cases.

Microvascular reconstruction in the vessel depleted neck - A systematic review.

Surgical therapy is the gold standard in head and neck cancer treatment, whereas adjuvant radiation and chemotherapy may be indicated in advanced cases. Frequently, neck dissections, former flap anastomoses and irradiated tissue leave a neck depleted of recipient vessels. If further surgery becomes inevitable the surgeon is faced with a heavily pretreated surgical field asking for highly reliable solutions for microsurgical reconstruction. From September 2017 until October 2017, a standardised review on the literature of the databases PubMed, Cochrane Library and Web of Science was performed. The primary research led to 1.614 articles, an evaluation by comprehensive content resulted in 26 suitable articles. Overall, 325 patient cases were included in the study. 112 postsurgical complications were noted (34.5%) and 12 deaths were reported (3.7%). The most common flaps harvested were the anterolateral-thigh flap (n = 85, 25.8%), the radial forearm flap (n = 78, 23.7%) and the flaps from the trunk (n = 31, 9.4%). The arteries most frequently used for anastomosis were the internal mammary artery (n = 81; 28%), the transverse cervical artery (n = 46; 15.9%) and the superficial temporal artery (n = 43; 14.9%). The cephalic vein (n = 84; 25.9%), the internal mammary vein (n = 79; 24.4%) and the superficial temporal vein (n = 50; 15.4%) were the most successfully applied veins.

Evaluation of a computed-tomography-based assessment scheme in treatment decision-making for isolated orbital floor fractures.

INTRODUCTION: Treatment decisions for fractures of the orbital floor are based on clinical appearance, ophthalmological examination, and computed tomography (CT) scans. In extensive fractures, decisions are easily made between conservative and surgical treatment. However, objective parameters are rare in inconclusive cases. MATERIALS AND METHODS: Our retrospective study included 106 patients with unilateral isolated orbital floor fractures. Correlations between preoperative ophthalmological examinations and specific CT parameters were performed. RESULTS: The defect size of the fracture appeared to be significantly associated with the presence of diplopia. CT-morphological parameters and preoperative ophthalmological results showed statistical significance for diplopia and incarceration of inferior rectus muscle (IRM), diplopia and displacement of IRM, decreased mobility and incarceration of IRM, and decreased mobility and displacement of IRM. DISCUSSION: Our clinical assessment scheme for CT scans of orbital floor fractures is aimed at facilitating treatment decision making using four CT-based variables. As critical size defects of the orbital floor of ≥2 cm2 are likely to cause clinically significant posterior displacement of the globe, resulting in enophthalmos, the proposed parameters offer a readily accessible and easy to evaluate scheme that helps to identify patients in need of surgical intervention.

Dental prevention and disease awareness in children with congenital heart disease.

OBJECTIVES: The importance of excellent oral health is known to be crucial in children with congenital heart diseases (CHD). Data about dental health and disease awareness is limited. This study aims to assess preventive measures taken to improve dental health in children with CHD and to gain insight into disease awareness and knowledge about the importance of oral health in children with CHD and to propose measures that could be taken. MATERIAL AND METHODS: Parents of 150 children with CHD were asked to complete a questionnaire containing specific questions about the preventive measures taken by the parents and dental and medical practitioners and their knowledge about underlying disease and the importance of oral health. RESULTS: Our results show an absence of information in parents concerning preventive measures and oral hygiene. Knowledge of the indications for antibiotic prophylaxis and for actually given medications was lacking. Preventive dental measures were not performed according to current guidelines. CONCLUSIONS: Knowledge of parents about the importance of oral health in children with CHD could be improved. However, specialized centers involving pediatric cardiologists and pediatric dentists could coordinate the education of parents at an early stage. Moreover, general dentists should be trained more frequently concerning the indications for antibiotic prophylaxis, in particular, and the dental care of children with chronic diseases, in general. Warning cards such as the heart pass should be issued to parents of children with CHD. CLINICAL RELEVANCE: The current study reveals the need for the structured training of medical and dental practitioners to support parents of children with CHD.

Site-specific gene expression patterns in oral cancer.

BACKGROUND: Squamous cell carcinomas (SCCs) are the most prevalent malignant tumours within the head and neck. Evidence exists that distinct genes are differentially regulated in SCCs of the oral cavity compared to other head and neck regions. Given this background, the aim of this study was to investigate whether such tumour site-specific gene expression can also be observed in different localizations within the oral cavity. METHODS: Using tissue microarrays (TMAs), we investigated 76 SCCs of the floor of the mouth, 49 SCCs of the tongue and 68 SCCs of other anatomic regions within the oral cavity. The expression of 17 genes involved in cell cycle and growth control (p16, p21, p27, p53, cyclin D1, EGFR, c-kit, bcl-6), cell adhesion (alpha-, beta-, and gamma-catenin), and apoptosis/stress response genes (Hif-1-alpha, Glut 1, CA IX, caspase, hsp70, XIAP) were investigated by means of immunohistochemistry. The data were subjected to chi2, interdependency and Kaplan-Meier analysis. RESULTS: Our study suggests a remote difference in the site-specific gene expression patterns of oral cancer. X-linked inhibitor of apoptosis (XIAP) showed a significantly higher expression (p <0.05) in SCCs of the floor of the mouth compared to SCCs of the tongue and other locations within the oral cavity. The increased XIAP expression was further associated with significantly decreased overall survival in all cases of SCCs of the oral cavity (p <0.05). Expression levels of p53, CA IX, beta-catenin, Hif-1-alpha, and c-kit were also observed to be inversely related between SCCs of the floor of the mouth and those of the tongue respectively, although these differences did not reach statistical significance. Overall and event-free survival did not differ in patients with T1/T2/N0 SCCs according to tumour localization. CONCLUSION: In summary, the protein expression patterns of SCCs of the oral cavity suggest the existence of a molecular and morphological spectrum of SCCs in the oral cavity. In particular the expression pattern of XIAP indicates distinct gene expression patterns between carcinomas of the floor of the mouth and oral tongue cancer. Further studies are needed to identify possible tumour site-specific factors that influence patient prognosis and management.

Classification of orbital exenteration and reconstruction.

Orbital exenteration (OE) is considered to be a mutilating surgical procedure reserved for relentlessly progressive neoplastic disorders or extensive facial trauma with unfavourable eye involvement. Malignant tumours, accounting for the majority of ablative orbital surgeries, may be caused by primary orbital tumours or secondarily by neoplasias from the surrounding skin, the maxillary sinus or intracranial malignomas. Orbital exenteration following trauma is mostly caused by penetrating globe defects or extended infections with the danger of intracranial effects. Thoughtful resection planning, the exploitation of reconstructive possibilities as well as the consideration of adjuvant therapy are essential to provide the patient with the best available treatment. As a multitude of reconstructive procedures exist, it is of crucial importance to offer a disease-tailored treatment to achieve a successful patient outcome. After retrospective analysis of 45 orbital exenteration cases within the last decade, we developed a defect-driven classification for ablative orbital therapy followed by a guideline for reconstructive procedures. The classification as well as the reconstruction guideline will help the surgeon to restore anatomic boundaries and to promote physiological and psychological recovery for the patient.

NOS1-, NOS3-, PIK3CA-, and MAPK-pathways in skin following radiation therapy.

BACKGROUND: Essential molecular pathways such as the MAPK pathway, NO system, or the influence of PIK3CA as an oncogene are known to regulate fundamental signalling networks. However, few knowledge about their role in the occurrence of wound healing disorders (WHD) following radiation therapy (RT) exists. This study aims to evaluate the expression profiles of specific molecular pathway marker genes. METHODS: Expression profiles of the genes encoding MAPK, NOS1, NOS3, and PIK3CA were analyzed, by RT-PCR, in specimens from patients with and without a history of RT to the head and neck. Clinical data on the occurrence of cervical WHDs were analyzed. RESULTS: Expression analysis of patients with postoperative WHDs revealed a significant increase in MAPK expression compared to the control group without occurrence of postoperative WHDs. PIK3CA showed a significantly increased expression in patients with a history of RT. Expression analysis of all other investigated genes did not reveal significant differences. CONCLUSIONS: This current study is able to show the influence of RT on different molecular pathways. This underlines the crucial role of specific molecular networks, responsible for the occurrence of long-term radiation toxicity such as WHDs. Additional studies should be carried out to identify possible starting points for therapeutic interventions.

Cytokeratin and protein expression patterns in squamous cell carcinoma of the oral cavity provide evidence for two distinct pathogenetic pathways.

Squamous cell carcinoma (SCC) of the oral cavity is a morphological heterogeneous disease. Various cytokeratin (CK) expression patterns with different prognostic values have been described, but little is known concerning the underlying biological cell mechanisms. Therefore, the present study investigated 193 cases of oral SCCs using immunohistochemistry for α/ß/γ-catenin, glucose transporter 1, caspase-3, X-linked inhibitor of apoptosis protein, hypoxia inducible factor-1α, carbonic anhydrase 9, heat shock protein (hsp) 70, mast/stem cell growth factor receptor, p21, p27, p16, p53, B-cell lymphoma 6, epidermal growth factor receptor, cyclin D1 and CK1, 5/6, 8/18, 10, 14 and 19. Expression patterns were analyzed with biomathematical permutation analysis. The present results revealed a significant association between the expression of low-molecular weight CK8/18 and 19 and a high-tumor grade, ß and γ-catenin expression, deregulated cell cycle proteins and a predominant localization of the tumor on the floor of the mouth. By contrast, expression of high-molecular weight CK1, 5/6, 10 and 14 was significantly associated with the expression of p21 and hsp70. In conclusion, the current study presents evidence for the existence of two parallel pathogenetic pathways in oral SCCs, characterized by the expression of low- and high-molecular weight CKs. Additional studies are required to demonstrate the extent that these results may be used to improve therapeutic regimens.