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.

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.

Evaluation of Different Patterns of Zygomaticoorbital Complex Fractures.

Study Design: Very few studies exist regarding the fracture pattern variability of the zygomaticoorbital (ZMO) complex. The retrospective evaluation of a large series of surgically treated unilateral ZMO fractures would in certain circumstances help intraoperative predictability and define sensitive indicators for open reduction and internal fixation. Objective: The aim of this study was to investigate the different fracture patterns after ZMO complex injury regarding the 5 anatomic sutures of the zygoma as well as the concomitance of the paranasal buttress and maxillary sinus wall fracture. Methods: The medical records of all patients with unilateral ZMO fractures who underwent surgical intervention in a single trauma center department between April 2015 and June 2020 were retrospectively reviewed. Demographic and anamnesis data, radiologic findings, and surgical reports were evaluated. According to the preoperative radiologic evaluation, ZMO fractures were classified as unisutural, bisutural, trisutural, tetrasutural, and complete based on the number of zygomatic sutures. The prevalence of various fracture patterns was analyzed. The impact of patient's age and trauma etiology on the fracture pattern was evaluated using descriptive statistical analysis. Results: The study included 492 patients with unilateral ZMO fractures, with a mean age of 49.93 years (SD = 20.66) and a male:female ratio of 2.23:1. The most affected age group was 19-44 years (41.67%) and tripping falls were the most common etiology (27.24%). Trisutural (57.32%) and unisutural fractures (23.17%) were the most common, followed by tetrasutural (8.94%), bisutural (8.54%), and complete fractures (2.03%). A trisutural fracture involving the zygomaticomaxillary suture, the infraorbital rim, and the zygomaticosphenoidal suture was the most common fracture pattern (52.03%). Most fractures were observed in the zygomaticosphenoidal suture (86.99%), followed by the infraorbital rim (74.59%) and the zygomaticomaxillary suture (68.29%). Fractures of the maxillary sinus wall and the paranasal buttress co-existed in 9.55% and 31.30% of all cases, respectively. No correlation was detected between age and fracture pattern (P = .4111). Tripping falls and bicycle accidents significantly influenced the fracture pattern (P < .0001). Conclusions: According to the results, knowledge of the fracture pattern variability of the ZMO complex could in certain circumstances designate CT or CBCT as mandatory before operating on ZMO fractures. Consequently, unnecessary incisions could be avoided. The high concomitance of paranasal buttress fracture also suggests its intraoperative surgical exploration. Further studies should correlate the clinical findings with indication for surgery and postoperative outcome for the different fracture patterns described.

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.

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.

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.

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.

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.