Hemifacial Microsomia Surgical Approach and Anotia Reconstruction: A Case Report.

BACKGROUND/AIM: Hemifacial microsomia (HFM) is the second most common congenital anomaly of the craniomaxillofacial region after the cleft lip and palate. This malformation is characterized by unilateral mandible and ear hypoplasia. Treatment varies and depends on different phenotypes. Severe deficiencies require multiple reconstructive surgeries to address facial asymmetries. This study aimed to review the surgical approach and evaluate the postoperative results of a case with right hemifacial microsomia and anotia. CASE REPORT: This is the case of a 35-year-old female patient who, after multiple graft operations in the right mandible due to hemifacial microsomia, was operated for auricle reconstruction. Initially, a three-dimensional custom made Medpor (porex) was used, covered by the superficial temporal fascia. Subsequently, due to inflammation and partial exposure of this porous polyethylene implant (PPI), a temporalis muscular flap along with the deep temporal fascia were used as a salvage operation. Ten months later, the patient underwent deep plane face lift combined with open rhinoplasty. Lefort I osteotomies and transoral lip lengthening through a transection of the levator nasi septi muscle were also performed. Ear helix reconstruction was completed with a rotation scalp flap after tissue expansion. The patient had an uncomplicated postoperative course with an aesthetically acceptable result. CONCLUSION: As a congenital disorder, hemifacial microsomia is present at birth and successful reconstruction is of fundamental importance for the smooth integration of these individuals into society. The multiple asymmetries, the affected topographic area of the face, as well as the onset in neonatal age constitute a challenge for reconstructive surgery.

AKT and PERP Show Higher Expression in Precancerous than in Malignant Skin Neoplasms: Profiling in an Animal Model of Sequential Skin Carcinogenesis.

The primary aim of this study was to evaluate the activation of the PERP and Akt oncogenes in the induction of skin cancer in FVB/N mice by a stepwise chemical process. Forty four-week-old female FVB/N mice were randomly divided into a control group (n = 8) and two experimental groups (group A: n = 16, group B: n = 16). In the study, the groups were subjected to a two-stage carcinogenesis procedure. This consisted of an initial application of 97.4 nmol DMBA to shaved skin on the back, followed by applications of 32.4 nmol TPA after thirteen weeks for group A and after twenty weeks for group B. The control group received no treatment. Skin conditions were monitored weekly for tumor development. At the end of the experiment, the animals were euthanized for further tissue sampling. Examination of the skin lesions in the experimental groups showed a correlation with tumor progression, ranging from dysplasia to carcinoma. Tumor samples were examined both histologically and immunohistochemically. Notably, and PERP expression was higher in precancerous than in malignant tumors. The differences in expression between precancerous and benign tumors provide further evidence of a role for PERP and Akt in the transition from benign to malignant states. Our findings underscore the critical roles of PERP and Akt in the pathogenesis of skin cancer and suggest their potential as biomarkers for early detection and targets for therapeutic intervention.

Pleomorphic Adenoma of Minor Salivary Glands: a Rare Case Report.

Pleomorphic adenoma is a non-cancerous neoplasm that develops in the salivary glands. Originating from minor salivary glands, it is extremely uncommon and primarily affects females. The peak incidence is observed between 40 and 60 years of age. It usually presents as a slowly growing, painless, solid tumor that does not cause ulcers on the overlying mucosa. Here, a 47-year-old woman experienced repeated swelling on the buccal mucosa following surgical extraction of a pleomorphic adenoma three years ago. The swelling was solid with clearly defined boundaries. An excisional biopsy was conducted under general anesthesia, resulting in total mass removal. The histological evaluation revealed the existence of a recurring pleomorphic adenoma. This instance emphasizes the significance of addressing this entity as a potential etiology for persistent painless and intraoral swellings.

C-Jun Transcription Factor Oncogenic Activation in Oral Carcinoma.

INTRODUCTION: Oral carcinogenetic is based on a variety of genomic imbalances (gross chromosome or specific gene alterations) that drive the normal oral mucosa to its neoplastic/dysplastic epithelial form and finally to a totally malignant tissue transformation. In this multi-step procedure, down-regulation of suppressor genes combined with overactivation of oncogenes are two crucial and partially early genetic events involved in the onset and progression of neoplastic/malignant epithelia transformation. More specifically, deregulation of strong transcription factors negatively affects the normal expression of a broad spectrum of genes that are involved in cell proliferation and signalling transduction to the nucleus. OBJECTIVE: The purpose of the current molecular review was to explore the c-Jun (chromosome location: 1p32-p31) transcription factor transformation mechanisms to oncogene in oral squamous cell carcinoma (OSCC). MATERIAL AND METHOD: A systematic review of the literature was carried out by searching in PubMed international database. The year 2010 was set as a prominent time limit for the publication date of the articles in the majority of them, whereas specific references of great importance and historical value in the field of the c-Jun gene discovery and analysis were also included. The following keywords were used: c-Jun, oncogene, signaling pathway, oral, carcinoma, transcription. A pool of 45 important articles were selected for the present study at the basis of combining molecular knowledge with new targeted therapeutic strategies. RESULTS: C-Jun - as a part of the c-Jun/c-Fos transcription factors' complex -critically regulates the expression levels in a variety of genes inside the cellular microenvironment. A broad spectrum of malignancies, including OSCC, demonstrate c-Jun alterations driving the gene to its oncogenic phenotype. Interestingly, c-Jun oncogenic activation is mediated by high-risk human papilloma virus (HR-HPV) persistent infection in significant subsets of these malignancies. CONCLUSIONS: C-Jun was the first oncogene - acting as a strong transcription factor - that was discovered and cloned 35 years ago. C-Jun is the living history of oncogenes and its discovery marks a significant step in the evolution of molecular biology.

FGFR2 and NOTCH1 Expression Inversely Correlated in Progressive Cutaneous Carcinogenesis in an Experimental Mouse Model.

Cutaneous squamous cell carcinoma (cSCC) is a common and increasingly prevalent form of skin cancer, posing significant health challenges. Understanding the molecular mechanisms involved in cSCC progression is crucial for developing effective treatments. The primary aim of this research was to evaluate the activation of NOTCH1 and FGFR2 oncogenes in inducing skin cancer in FVB/N mice through a stepwise chemical process. Forty female FVB/N mice, aged four weeks, were randomly divided into a control group (n = 8) and two experimental groups (group A: n = 16, group B: n = 16). This study involved subjecting the groups to a two-stage carcinogenesis procedure. This included an initial application of 97.4 nmol DMBA on shaved skin on their backs, followed by applications of 32.4 nmol TPA after thirteen weeks for group A and after twenty weeks for group B. The control group did not receive any treatment. Their skin conditions were monitored weekly to detect tumor development. After the experiment, the animals were euthanized for further tissue sampling. The examination of skin lesions in the experimental groups showed a correlation with tumor progression, ranging from dysplasia to carcinoma. Tumor samples were assessed both histologically and immunohistochemically. Notably, FGFR2 expression was higher in benign, precancerous, and malignant tumors compared to normal tissue. NOTCH1 expression was only elevated in benign tumors compared to normal tissue. This study demonstrates a clear correlation of FGFR2 expression and the progression of cutaneous neoplasms, while NOTCH 1 expression is inversely correlated in FVB/N mice. This suggests an early involvement of these oncogenes in the development of skin tumors.

Porcine-derived Acellular Dermal Matrix for Temporary Soft Tissue Coverage in Locally Advanced Angiosarcoma of the Face - A Soft Tissue Odyssey?

BACKGROUND/AIM: Angiosarcomas of the face are rare but present significant treatment challenges due to their origin in the supportive tissues of blood or lymphatic vessels. Achieving optimal balance between oncological efficacy and aesthetic outcomes requires a multidisciplinary approach, particularly in cases where radical R0 resection is necessary. Delays often occur, especially during histopathological examinations, which can complicate primary plastic reconstruction before definitive pathological findings. CASE REPORT: To address this issue, we present a case with the use of porcine-derived acellular dermal matrix for temporary soft tissue coverage as a viable option in a case of angiosarcoma of the face. This is particularly useful in situations where frozen sections risk the loss of critical anatomical structures and intraoperative diagnosis is not feasible. This approach allowed for satisfactory wound coverage and granulation during diagnostic phases, paving the way for oncologically manageable situations and functional rehabilitation. CONCLUSION: Temporary soft tissue coverage with porcine-derived acellular dermal matrix is a valuable option in tumor surgery of rare and complex situations.

Fibula Grafting for Oromandibular Reconstruction and its Effect on Patient Quality of Life - A Scoping Review.

Fibula osteoseptocutaneous flap has been widely used for oncologic bony reconstruction of both the mandible and maxilla. Early and late morbidities of the donor side such as leg weakness, ankle instability, limited ankle mobility, tibial stress fractures or incision area pain are well documented; however, there is a lack of information about the effects of fibula grafting on patient quality of life. To address this issue, a scoping literature search in the PubMed electronic database was performed to identify all relevant studies and reviews in the period between 2010 and 2022. The potential discomforts after free fibula grafting and their impact on different domains of everyday living were identified and evaluated. The present literature review indicates that donor site morbidity can negatively impact patients' quality of life, albeit generally classified as minor. However, the functional and aesthetic benefits of oromandibular reconstruction clearly outweigh the associated sequelae. Nevertheless, the authors of this review highlight the importance of a comprehensive clinical evaluation of the donor site besides the recipient site during follow-up examinations. This would help to subjectively evaluate the functional and esthetical limitations of a patient's site and promptly detect morbidities that could lead to long-term complications.

Solitary Fibrous Tumor of the Masticator Space with Unusual Extension: a Case Report.

Background: We present the case of a patient with solitary fibrous tumor of the masticator space with unusual extension. Case presentation: A 43-year-old woman presented with a painless mass with intraoral extension on the right cheek. The B-scan sonograph and magnetic resonance imaging revealed the extension of the tumor. The biopsy performed under local anesthesia raised the suspicion of a solitary fibrous tumor. Tumor excision included a preoperative tumor embolization. The surgical removal of the tumor included a partial parotidectomy on the right side, insertion of masseteric and temporalis muscle, resection of the middle part of the zygomatic bone and stabilization of the bone with a plate, mobilization of the tumor from the maxillary sinus and the pterygopalatine fossa through an endoscopic approach and an approach via partial resection of the anterior wall of the maxillary sinus after identifying and sparing the infraorbital nerve. Ôhe histological findings confirmed the diagnosis of solitary fibrous tumor. The patient's treatment completed with radiation therapy, and 2.5 years later, there was recurrence in the right temporal area. Conclusion:To our knowledge, this is the second reported case of solitary fibrous tumor arising in the masticator space and the only case with extension intraorally and in the paranasal sinuses. Tumor embolization and complete surgical excision are the most frequently recommended treatments.

Tumor ablation including carotid artery resection and simultaneous reconstruction: A retrospective study.

The study purpose is to review the surgical approach and evaluate the results in cases of head and neck malignancies with internal carotid artery invasion. The anatomical site of the primary tumor varied including a fixed massive metastatic neck disease of an occult intraoral carcinoma of the right tonsil, a recurrent metastatic neck tumor after laryngectomy for glottic primary carcinoma and a metastatic malignant melanoma of an unknown primary origin. In all cases carotid artery was invaded and therefore resected. An extended Javid shunt was performed between common carotid artery (CCA) and internal carotid artery (ICA) followed by CCA grafting with an interposition saphenous vein graft. In one case the vagus nerve was also grafted with an interposition sural graft. The total patient number was three. By clinical examination, follow-up and duplex scanning, the patency of the carotid grafts, vascular and non-vascular complications, disease recurrence and survival were analysed. Additionally, there was a double metachronous reconstruction for recurrence, giving the opportunity to study the graft adoption and response to disease. Internal carotid artery invasion portends a poor prognosis. The results show that carotid artery resection followed by the appropriate reconstruction yields a chance for cure or can provide reasonable palliation.

Influence of analytical procedures on miRNA expression analyses in saliva samples.

Aim of this study was to demonstrate the influence of different analytical procedures and techniques on the resulting miRNA expression profile in healthy control subjects and tumor patients using the oral squamous cell carcinoma (OSCC) model and to demonstrate the technical and biological reproducibility. Body fluids such as saliva are suitable for non-invasive miRNA analysis because ubiquitously circulating miRNA can be found in them. It was technically possible to distinguish between healthy and diseased samples based on the miRNA expression profile found. Regardless of the methodology used, good technical reproducibility of the results seems to be achievable. On the other hand, biological reproducibility was inadequate, which is why prompt sampling and sequencing is recommended. The data indicate that malignant lesions can be detected using miRNA signatures extracted from saliva. This could stimulate further research to establish standardized protocols and kits for sample collection, miRNA extraction, sequencing and interpretation of results.

Extracranial Hypoglossal Schwannoma: Case Report and Literature Review.

BACKGROUND: Schwannomas are solitary neurogenic tumors originating from the myelin sheath of peripheral nerves. Extracranial hypoglossal schwannomas comprise <5% of all head and neck schwannomas and can mimic submandibular salivary gland tumors. CASE REPORT: We report the diagnostic imaging, surgical treatment, and histopathological findings of a rare case of extracranial schwannoma of the hypoglossal nerve in a 73-year-old female, presented with an asymptomatic swelling in the left submandibular region that had been persisted for approximately three years. CONCLUSION: Accurate diagnosis of this rare clinical entity requires comprehensive diagnostics. The optimal therapeutic strategy is nerve-sparing surgical excision, although it can be challenging.

Investigation of Genetic Association Between a High Activity Variant of Cathepsin G and Risk for Basal Cell Carcinoma.

BACKGROUND/AIM: Cathepsin G (CTSG) has been identified as an inhibitor of breast, bladder, and colorectal cancers. The G allele of the N125S (A/G, rs45567233) functional polymorphism of the CTSG gene confers increased serum CTSG activity and has been associated with cardiovascular and neurovascular diseases. This study examined the possible correlation between the pathogenesis of basal cell carcinoma (BCC) and the functional polymorphism CTSG N125S. PATIENTS AND METHODS: A total of 197 DNA samples were examined, comprising 98 BCC patients and 99 control samples of Greek origin. The CTSG N125S polymorphism was molecularly genotyped using PCR amplification, followed by enzyme digestion, and agarose gel electrophoresis of the amplified DNA fragments. RESULTS: There was no statistically significant difference in the genotypic and allelic frequencies between the patient and the control groups. CONCLUSION: There is no association between the CTSG N125S polymorphism and pathogenesis of BCC.

Management of head & neck sarcomas in adults: A retrospective study.

The research purpose is to review the surgical approach and evaluate the results in adult patients with head and neck sarcomas. The histopathology varied, including two leiomyosarcomas, six malignant fibrous histiocytomas, two malignant peripheral nerve sheath tumors, four dermatofibrosarcomas protuberans, three osteosarcomas, two angiosarcomas, one liposarcoma, one Ewing sarcoma, one synovial sarcoma, two unclassified/non-differentiated sarcomas and one solitary fibrous tumor. Surgical resection included maxillectomy, mandibulectomy, craniectomy, parotidectomy, scalp resection, face skin resection and laminectomy. The reconstruction was performed with one rectus abdominis flap, four radial forearm flaps, two latissimus dorsi flaps, two vascularized fibula flaps, two pectoralis major myocutaneous flaps, two trapezius flaps, two temporalis flaps, seven scalp flaps and two nasolabial flaps. The total patient number was 24. The hospitalization was uncomplicated, followed by postoperative radiotherapy in the majority of cases. In a mean 15-year follow-up period, 11 patients are still alive and disease-free. There were four recurrences treated with palliative radiotherapy. The surgical approach for head and neck sarcomas, including the achievement of a functionally acceptable result by organ sparing techniques, remains challenging. Wide resection combined with the appropriate reconstruction, particularly with microsurgical techniques, and followed by adjuvant radiotherapy or chemotherapy offer improved prognosis and quality of life.

EGFR and HER-2 oncogenes expression in an experimental model of two-stage chemically induced carcinogenesis in mouse skin.

The aim of the study was to investigate the expression of EGFR and HER-2 oncogenes using an experimental two stage chemically induced carcinogenesis protocol on the dorsal skin in FVB/N mice. Forty female FVB/N mice 4 weeks old, were grouped into one control (n = 8) and two experimental groups (Group A: n = 16, Group B: n = 16) following a randomization process. Two-stage carcinogenesis protocol, was implicated, including an initial treatment with 97.4 nmol DMBA on their shaved dorsal skin and subsequent treatments of 32.4 nmol TPA applications after 13 weeks for Group A and after 20 weeks for Group B. The control group C, received no treatment. Skin was examined weekly for tumor development. Post-experiment, animals were euthanized for tissue analysis. The histological status of the skin lesions in the experimental groups corresponded well with tumour advancement (from dysplasia to poorly-differentiated carcinoma). Tumour sections were evaluated histologically and immunohistochemically. EGFR expression was found significantly higher in precancerous and malignant tumours (p = 042 and p = 008 respectively), while tended to be higher in benign tumours (p = 079), compared to normal histology. Moreover, mean percentage of EGFR positive expression in malignant tumours was significantly higher than in benign tumours (p < 001). HER-2 expression was found significantly higher in precancerous and malignant tumours (p = 042 and p = 015 respectively), while tended to be higher in benign tumours (p = 085), compared to normal histology. Furthermore, mean percentage of HER-2 positive expression in malignant tumours was significantly higher than in benign tumours (p = 005). The study demonstrated that in FVB/N mice subjected to a two-stage chemically induced carcinogenesis protocol, there was a significant increase in the expression of EGFR and HER-2 oncogenes in precancerous and malignant skin lesions compared to normal tissue. This suggests a potentially early role of these oncogenes in the progression of skin tumours in this model.

Evaluation of Five-year Overall Survival Rates Among 18,331 Head and Neck Cancer Patients Exposed to Different Targeted Therapies Through Real-world Data in a Case-controlled Study.

BACKGROUND/AIM: Targeted therapy is an important and fast developing aspect of modern tumor therapy including therapy of head and neck cancer (HNC). Surgically treated patients often experience significant limitations to their ability to swallow, speak, or mimic expressions. In cases of recurrent tumors or palliative situations, targeted therapies such as immune checkpoint inhibitors (ICI) are frequently employed. This study compared different targeted therapies focusing on survival probability. PATIENTS AND METHODS: Data from patients with head and neck cancer treated with different therapy regimens from the TriNetX network were analyzed. Two groups were formed: Cohort I received one targeted therapy, whereas patients in cohort II received a different targeted therapy. Cohorts I and II were matched 1:1 with respect to certain confounders. After defining the primary outcome as "death", a Kaplan-Meier analysis was performed, and the risk ratio (RR), odds ratio (OR), and hazard ratio (HR) were calculated. RESULTS: A total of 18,331 patients with HNC treated with targeted therapy were analyzed. Patients treated with VEGF inhibitors had a significantly longer overall survival than patients treated with c-MET or EGFR inhibitors. Patients treated with PI3K inhibitors showed a significantly reduced survival probability compared to those treated with c-MET, mTOR, and RET inhibitors. CONCLUSION: EGFR inhibitors are one of the most frequently used targeted therapies in HNC. However, in the present analysis, a survival advantage of patients treated with c-MET inhibitors or VEGF inhibitors was observed compared to those treated with EGFR inhibitors.

Midface microvascular reconstruction after maxillary complex tumor resection: A retrospective study.

The study purpose is to review the surgical approach and evaluate the results in managing patients with advanced midface and maxillary complex tumors. The most common anatomical site of the primary tumor was the maxilla, sometimes with extension to the orbit and anterior fossa, parotid and middle ear or even the lip. Surgical resection included maxillectomy in the majority of cases, combined with orbital exenteration or orbitectomy and anterior fossa resection. Parotidectomy and mastoidectomy/core petrosectomy were also performed. Reconstruction was performed with radial forearm osteocutaneous free flap, latissimus dorsi myocutaneous flap with scapular bone flap, lengthening temporalis myoplasty, rectus abdominis free flap, anterolateral thigh flap, in combination with temporalis and vastus lateralis, as well as pectoralis major myocutaneous flap. A total of 36 midface tumor excisions were performed, followed by the appropriate reconstruction. The average follow-up period was 15 years. To date, 23 patients are disease free, while 6 patients presented disease recurrence and 7 patients died during the 15-year follow-up period. Surgical resection remains the gold standard for midface tumors management. When safely performed, combined with microvascular and dynamic face reconstruction, surgery can offer improvement in quality of life and prolong the overall survival.

Sex-specific Real-World 5-year Overall Survival Rates for (Radio)chemotherapy, Targeted Therapy, and Combinations in Patients With Head and Neck Cancer.

BACKGROUND/AIM: Sex-specific medicine, an emerging field in healthcare, has gained significant recognition and importance in recent years. To the best of our knowledge, there are currently no valid data on the influence of sex on 5-year overall survival of patients with head and neck cancer undergoing (radio)chemotherapy, targeted therapy, and combination treatments, using Real-World Data. We hypothesize that sex has a significant impact on 5-year overall survival across different therapy regimens for head and neck cancer. PATIENTS AND METHODS: Data from head and neck cancer patients treated with different regimens from the TriNetX network were analyzed. Two groups were formed: Cohort I (female) and cohort II (male), which were matched 1:1 with respect to certain confounders. After defining the primary outcome as "death", a Kaplan-Meier analysis was performed, and the risk ratio (RR), odds ratio (OR) and hazard ratio (HR) were calculated. RESULTS: A total of 16,529 patients with OSCC were analyzed. This retrospective case-matched analysis found a tendency for female patients to have a greater 5-year overall survival probability than male patients with respect to the various therapeutic regimens for OSCC. CONCLUSION: There is an urgent need for more personalized medicine in patients with head and neck cancer due to the limited data available. It is still questionable whether therapies are equally effective in men and women, although, according to the guidelines, the treatments are mostly the same for both sexes.

Ibuprofen Reduces 5-Year Overall Survival of Head and Neck Cancer Patients With Immunotherapy - A Retrospective Case-controlled Real-World Data Analysis of 10,000 Patients.

BACKGROUND/AIM: Resistance to immunotherapy can be explained by an abnormal microbiome of the gut. In Europe in particular, the use of ibuprofen, with or without proton-pump inhibitors to protect the gastric mucosa, is widespread. This study aimed to investigate the impact of ibuprofen use on the effectiveness of immunotherapy in patients with head and neck carcinoma. PATIENTS AND METHODS: Data from patients with head and neck carcinoma (ICD-10-Codes: C00-C14) receiving pembrolizumab, from the TriNetX network, were analyzed. Two groups were formed for the analyses: Cohort I received ibuprofen at least once within 6 months before and after immunotherapy, whereas patients in cohort II received ibuprofen with proton-pump inhibitors or no ibuprofen at all. Cohorts I and II were matched 1:1 with respect to age, sex, lymph node metastases, nicotine dependence, alcohol dependence, and body mass index (BMI). The primary outcome was death and a Kaplan-Meier analysis was performed, and the risk ratio (RR), odds ratio (OR), and hazard ratio (HR) were calculated. RESULTS: The analysis showed that 823 patients with ibuprofen and 724 patients without ibuprofen died within 5 years, showing a significant risk difference of 5.3% (p=0.001). The RR was 1.137 [95% confidence interval (CI)=1.053-1.227], OR was 1.245 (95% CI=1.093-1.418), and HR was 1.202 (95%CI=1.088-1.329). CONCLUSION: Ibuprofen significantly decreases the drug effectiveness of immunotherapy and may be related to changes in the human microbiome. However, further prospective, randomized, and double-blind studies are needed to validate our data and to adequately address confounders.

Association of Polymorphisms in the Genes of Angiotensinogen and Angiotensin Receptors With Risk for Basal Cell Carcinoma.

BACKGROUND/AIM: Basal cell carcinoma (BCC) has been genetically associated with an increased expression of angiotensin-converting enzyme (ACE), an important factor of the renin-angiotensin system which produces vasoconstrictor angiotensin II. Other factors of this system include angiotensinogen (AGT) and angiotensin receptors AGTR1, AGTR2. We investigated the possible association of BCC with genetic variability in the AGT, AGTR1 and AGTR2 genes. MATERIALS AND METHODS: DNA samples of 190 Greeks were studied, including 91 patients with BCC and 99 matched healthy controls. Molecular genotyping of patients and controls was performed for the polymorphisms AGT M235T, AGTR1 A1166C and AGTR2 G1675A. RESULTS: The mutant T allele that increases AGT gene expression was detected in two-fold increased frequency in BCC patients in comparison to healthy controls (p <0.001). On the contrary, no significant difference was observed in AGTR1 and AGTR2 variants between patients and controls. CONCLUSION: Increased expression of AGT may be associated with BCC.