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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Association of polymorphisms in Tumor Necrosis Factor Alpha and Beta genes with increased risk for oral cancer.

BACKGROUND: In light of the recently found contribution of inflammation-related factors to oral oncogenesis, the possible correlation of tumor necrosis factor alpha and beta genes (TNF-alpha and TNF-beta) with risk of oral cancer was investigated. MATERIALS AND METHODS: DNA samples of 160 German and Greek patients with oral squamous cell carcinoma and 153 healthy controls of equivalent age, gender and ethnicity were studied. The functional polymorphisms TNF-alpha (-308 G/A) and TNF-beta (252 G/A), which affect gene expression, were investigated by restriction fragment length polymorphism analysis. RESULTS: The frequencies of high expression A2 (-308A) TNF-alpha allele and high expression B1 (252G) TNF-beta allele were significantly increased in cancer patients compared to controls (respectively: 62.2% versus 14.7%, p<0.0001; OR 8.65, 95% CI 5.74-13.04 and 66.9% versus 15.7%, p<0.0001; OR 10.92, 95% CI 7.4-16.2). Three combined TNF-alpha/TNF-beta genotypes (A2A2/B1B1, A1A2/B1B2, A1A2/B1B1) were over-represented in cancer patients (p<0.001). No significant differences in allele frequencies were detected among most subgroups of patients divided in regard to cancer stage, family history for cancer or thrombosis, smoking or heavy alcohol consumption habits. CONCLUSION: This study showed a strong association of TNF-alpha and TNF-beta high expression alleles with increased risk of oral cancer. These findings are in accordance with previously observed high TNF-alpha levels in serum of patients with oral cancer in comparison to healthy controls.

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.

A DNA polymorphism of stromal-derived factor-1 is associated with advanced stages of oral cancer.

BACKGROUND: Stromal derived factor-1 (SDF-1), a protein related to angiogenesis and inflammation, has been correlated with the progression of a number of malignancies, but not with oral squamous cell carcinoma. In light of the known contribution to the development of oral cancer of other gene polymorphisms for proteins responsible for angiogenesis, inflammation and thrombosis, this study investigated whether the G801A polymorphism in the SDF-1 gene is associated with this malignancy. PATIENTS AND METHODS: The G801A polymorphism was examined by restriction fragment length polymorphism analysis in DNA samples from 159 patients with oral squamous cell carcinoma and 101 matched healthy controls. RESULTS: The detected allele frequency of the "high production related" A allele in the control group was 25.3%. There was a slight decrease in allele frequency in patients (18.6%), but it was not statistically significant. The same pattern was observed in subgroups of patients in regard to smoking habits and family history of cancer or thrombosis. Interestingly, in comparison to controls, the A allele frequency was significantly lower in patients with advanced cancer stages III and IV (12.5%, p=0.005) and in patients with alcohol abuse (12.5%, p=0.02). CONCLUSION: The G801A polymorphism of the SDF-1 gene is associated with advanced stages of oral cancer, especially in alcohol abusers.

The interleukin-10 (-1082A/G) polymorphism is strongly associated with increased risk for oral squamous cell carcinoma.

BACKGROUND: Increased levels of interleukin-10 (IL-10) have been observed in patients with oral cancer, possibly as a result of suppression of the immune response. Based on this, the -1082A/G polymorphism, which influences IL-10 gene expression level, was investigated in regard to its possible association with risk for oral cancer. PATIENTS AND METHODS: The polymorphism was examined in DNA samples of 144 patients with oral squamous cell carcinoma and 141 healthy controls of equivalent gender, age and ethnicity. RESULTS: The detected allele frequencies for the high expression G allele were significantly higher in patients compared to controls (34.7% versus 21.3%, respectively, p=0.0004), as well as in patients that were smokers but not those that were heavy alcohol consumers. This highly significant difference in G allele frequency was mainly due to the increase of AG heterozygotes in patients compared to controls (OR 3.05, 95% CI 1.84-5.05). CONCLUSION: These findings suggest that the high expression G allele of the -1082A/G polymorphism of the inflammation and angiogenesis-related IL-10 is strongly associated with increased risk for oral cancer.

Angiotensinogen polymorphism is associated with risk for malignancy but not for oral cancer.

BACKGROUND: In light of the recently found contribution of angiogenic and inflammation-related factors to malignancies, this study investigated the possible association of the angiotensinogen gene (AGT) with increased risk of oral cancer. MATERIALS AND METHODS: The M235T polymorphism, which influences AGT gene expression, was evaluated by restriction fragment length polymorphism analysis in the DNA samples of 163 German and Greek patients with oral squamous cell carcinoma (OSCC) and 124 healthy controls of equivalent gender, ethnicity and age. RESULTS: No significant difference of the mutant (235T) allele, which results in higher AGT gene expression, was observed in the whole patient group in comparison with the normal controls. Similarly, compared to the controls no significant difference of either allele or carrier frequency was detected in almost every subgroup of patients. Only in the subgroup of patients with a positive family history of cancer was a significant increase of mutant T allele and carrier frequencies observed, compared to the controls (50% vs. 36.7% and 79.3% vs. 61.3%, respectively, p < 0.05 in both cases). In this particular subgroup of patients the odds ratio for OSCC of TT homozygotes was 3.57 (CI 95% 1.2-10.62), while for the MT heterozygotes it was 2.41 (CI 95% 1.06-5.49). CONCLUSION: This study did not reveal an association of the AGT M235T polymorphism with oral oncogenesis, but certainly suggested a possible association of this specific polymorphism with other types of cancer. The present findings support a previous suggestion that the pathway of oral oncogenesis is probably based on angiotensin-converting enzyme and bradykinin interaction and not on AGT and angiotensin peptides.