Functional Reconstruction of a Hemiglossectomy Defect With an Innervated Musculocutaneous Submental Artery Island Flap.

This report presents the use of an innervated musculocutaneous submental artery island flap (MSAIF) for the functional reconstruction of a hemiglossectomy defect, with the aim of preserving the volume and mobility of the reconstructed tongue to facilitate swallowing and intelligible speech. A 30-year-old male patient diagnosed with T3N0 stage squamous-cell carcinoma of the tongue underwent hemiglossectomy and ipsilateral I-IV selective neck dissection. For reconstruction, an innervated MSAIF with a 9x4 cm skin paddle, including the left submental vessels, ipsilateral anterior belly of the digastric muscle, mylohyoid muscle, and mylohyoid nerve, was harvested and inserted into the tongue defect. Postoperative healing at both donor and recipient sites proceeded without complications. At a three-year follow-up, the MSAIF has maintained its volume, mobility, and contractility. The patient remains disease-free and reports satisfaction with his swallowing and speech capabilities. The innervated MSAIF represents a reliable and cost-effective reconstruction approach for hemiglossectomy defects, showing favorable results in both swallowing and speech.

Phase II Window Study of Olaparib Alone or with Cisplatin or Durvalumab in Operable Head and Neck Cancer.

Purpose: We conducted a phase II randomized noncomparative window of opportunity (WOO) trial to evaluate the inhibition of cellular proliferation and the modulation of immune microenvironment after treatment with olaparib alone or in combination with cisplatin or durvalumab in patients with operable head and neck squamous cell carcinoma (HNSCC). Experimental Design: Forty-one patients with HNSCC were randomized to cisplatin plus olaparib (arm A), olaparib alone (arm B), no treatment (arm C) or durvalumab plus olaparib (arm D). The primary endpoint was to evaluate the percentage of patients in each arm that achieved a reduction of at least 25% in Ki67. Secondary endpoints included objective response rate (ORR), safety, and pathologic complete response (pCR) rate. Paired baseline and resection tumor biopsies and blood samples were evaluated for prespecified biomarkers. Results: A decrease in Ki67 of at least 25% was observed in 44.8% of treated patients, as measured by quantitative immunofluorescence. The ORR among treated patients was 12.1%. pCR was observed in 2 patients. Two serious adverse events occurred in 2 patients.Programmed death ligand 1 (PD-L1) levels [combined positive score (CPS)] were significantly higher after treatment in arms A and D. Expression of CD163 and colony-stimulating factor 1 receptor (CSF1R) genes, markers of M2 macrophages, increased significantly posttreatment whereas the expression of CD80, a marker of M1 macrophages, decreased. Conclusion: Preoperative olaparib with cisplatin or alone or with durvalumab was safe in the preoperative setting and led to decrease in Ki67 of at least 25% in 44.8% of treated patients. Olaparib-based treatment modulates the tumor microenvironment leading to upregulation of PD-L1 and induction of protumor features of macrophages. Significance: HNSCC is characterized by defective DNA repair pathways and immunosuppressive tumor microenvironment. PARP inhibitors, which promote DNA damage and "reset" the inflammatory tumor microenvironment, can establish an effective antitumor response. This phase II WOO trial in HNSCC demonstrated the immunomodulatory effects of PARP inhibitor-induced DNA damage. In this chemo-naïve population, PARP inhibitor-based treatment, reduced tumor cell proliferation and modulated tumor microenvironment. After olaparib upregulation of PD-L1 and macrophages, suggests that combinatorial treatment might be beneficial. Synopsis: Our WOO study demonstrates that preoperative olaparib results in a reduction in Ki67, upregulation of PD-L1 CPS, and induction of protumor features of macrophages in HNSCC.

Prosthodontic restoration of a COVID-19 associated mucormycosis defect: A clinical report.

INTRODUCTION: Coronavirus Disease 2019 (COVID-19) pandemic brought the clinical practice of dentistry and prosthodontics at the threshold of a new era, due to the increasing prevalence of a relative rare condition normally affecting the immunocompromised patients. AIM: The aim of this clinical case report is to briefly describe the etiopathogenesis, the surgical and prosthodontic management of this evolving medical condition emphasizing the emerging role of the maxillofacial prosthodontist in restoring the patients' well-being. METHODS AND RESULTS: The surgical and prosthodontic rehabilitation of a COVID-19 infected patient with a mucormycotic lesion of the maxilla will be presented. CONCLUSION: The role of the maxillofacial prosthodontist is important in alleviating this severe COVID-19 associated morbidity.

Effect of Low-level Light Therapy on Post-operative Healing of Secondary Chronic Osteomyelitis of the Jaws - A Prospective Study.

Introduction: Osteomyelitis of the jaws is a common disease of the maxillofacial region. The goal of treatment is to alleviate pain, reduce infection, inhibit the progression of the disease and induce bone and mucosal healing. In addition to surgical management and antibiotic and oxygen hyperbaric therapy, new therapeutic strategies for the treatment of osteomyelitis are developed. One of the novel approaches is photobiomodulation therapy or low-level light therapy (LLLT). Materials and Methods: After surgical treatment, experimental group patients (n = 4) were treated with LLLT for five sessions with an extraoral pulsed 635-nm LED lamp (Repuls7, Repuls Lichtmedizintechnik GmbH, Austria), maximum output power: 140 mW/cm2, frequency: 2.5 Hz, duty cycle: 50%. Clinical achievement and patient pain perception (through Visual Analogue Scale score) were evaluated at 1-, 3- and 6-month follow-up appointments and compared with control group (n = 4) patients, treated with standard therapy. Results: At three and six months, clinical achievement was better in patients treated with LLLT. Pain and discomfort resolution was significantly greater in the experimental group. Discussion: Taking into consideration the results of this study, it can be concluded that LLLT shows potential for improving clinical outcome of surgical and medical treatment of secondary chronic osteomyelitis of the jaws. Furthermore, pain and discomfort were significantly reduced in patients treated with LLLT. Further research with a larger sample size is needed to obtain a more accurate insight into this promising field.

Effectiveness of prosthetic rehabilitation and quality of life of older edentulous head and neck cancer survivors following resection of the maxilla: a cross-sectional study.

PURPOSE: To evaluate the effectiveness of prosthetic rehabilitation, as well as the quality of life (QOL) of older edentulous maxillectomy patients. METHODS: Effectiveness of the complete denture obturator prosthesis and QOL of N = 44 older edentulous patients who had resection of the maxilla and were restored with a definitive prosthesis that was in use for a minimum of 1 year was assessed using three instruments: European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire (QLQ-C30), Head and Neck Cancer Module (QLQ-HN35), and Obturator Functioning Scale (OFS). Data analysis was performed by one-way analysis of variance (ANOVA) on ranks, Spearman rank-order correlation, and hierarchical multivariable rank regression at α = .05 level of significance. RESULTS: Participants' gender (P < .001), adjuvant treatment (P = .016), surgical approach (P = .017), size of the maxillary defect (P = .028), participants' prosthetic history (P = .047), and dental status of the mandible (P = .038) were significantly related to the self-reported effectiveness of the complete denture obturator prosthesis. Perceived functioning of the prosthesis (P = .001), participants' gender (P = .002), the American Society of Anesthesiologists (ASA) physical status (P = .027), and surgical approach (P = .039) were significant predictors of QOL. CONCLUSION: Restoration of the edentulous maxillectomy defect is challenging. An effective definitive complete denture obturator appeared to be the strongest predictor for advanced quality of life in older maxillectomy patients. The physical status of the older participants significantly affected the overall QOL, but did not influence the self-reported functioning of the complete denture obturator prosthesis.

Quality of life in patients with soft palate resection: The relationship between reported functional prosthetic outcomes and the patient's psychological adjustment.

STATEMENT OF PROBLEM: Tumors of the soft palate and the adjacent tissues often create considerable soft palate defects that are challenging for the maxillofacial prosthodontist. Soft palate obturator prostheses can usually address functional and esthetic concerns; however, the effectiveness of the prosthetic rehabilitation in improving the patient's well-being and overall quality of life (QOL) has not been extensively researched. PURPOSE: The purpose of the present research was to evaluate the function of the prosthesis, to review the interrelation between sociodemographic, medical, and treatment (SMT) characteristics, QOL, and prosthesis functioning, and to analyze the role of the prosthesis in how the patient represents the illness and the psychological coping response. MATERIAL AND METHODS: Thirty-three patients who underwent resection of the soft palate and had been using a technically successful soft palate obturator prosthesis for at least 1 year were interviewed by means of 5 questionnaires: European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire (QLQ-C30), Head and Neck Cancer Module (QLQ-HN35), Obturator Functioning Scale (OFS), Illness Perceptions Questionnaire (IPQ-R), and Mental Adjustment to Cancer Scale (MAC). Data analysis was performed at α=.01. RESULTS: The QOL (r=-0.53, P=.001), personal control (r=-0.53, P=.001), negative adjustment to cancer (r=0.47, P=.005), treatment control (r=-0.55, P=.001), consequences (r=0.62, P<.001), and emotional representations (r=0.30, P=.009) were significantly related to prosthesis functioning. Better QOL was significantly related to prosthesis functioning (P=.006), age (P=.001), sex (P=.011), and type of soft palate defect (P=.009). The most important predictors of favorable soft palate obturator functioning were age (P<.001) and type of soft palate defect (P=.01). CONCLUSIONS: A patient-perceived effective soft palate obturator prosthesis was a significant predictor for advanced QOL, better adjustment to illness and illness-related disabilities, as well as the overall coping response to cancer.

Recurrence in Oral Premalignancy: Clinicopathologic and Immunohistochemical Analysis.

Oral leukoplakia (OL) has a propensity for recurrence and malignant transformation (MT). Herein, we evaluate sociodemographic, clinical, microscopic and immunohistochemical parameters as predictive factors for OL recurrence, also comparing primary lesions (PLs) with recurrences. Thirty-three patients with OL, completely removed either by excisional biopsy or by laser ablation following incisional biopsy, were studied. Selected molecules associated with the STAT3 oncogenic pathway, including pSTAT3, Bcl-xL, survivin, cyclin D1 and Ki-67, were further analyzed. A total of 135 OL lesions, including 97 PLs and 38 recurrences, were included. Out of 97 PLs, 31 recurred at least once and none of them underwent MT, during a mean follow-up time of 48.3 months. There was no statistically significant difference among the various parameters in recurrent vs. non-recurrent PLs, although recurrence was most frequent in non-homogeneous lesions (p = 0.087) and dysplastic lesions recurred at a higher percentage compared to hyperplastic lesions (34.5% vs. 15.4%). Lower levels of Bcl-xL and survivin were identified as significant risk factors for OL recurrence. Recurrences, although smaller and more frequently homogeneous and non-dysplastic compared to their corresponding PLs, exhibited increased immunohistochemical expression of oncogenic molecules, especially pSTAT3 and Bcl-xL. Our results suggest that parameters associated with recurrence may differ from those that affect the risk of progression to malignancy and support OL management protocols favoring excision and close monitoring of all lesions.

The role of M1 and M2 macrophage polarization in progression of medication-related osteonecrosis of the jaw.

OBJECTIVES: The aim of this study was to investigate the relationship between M1 and M2 macrophage polarization and clinical stage in patients with medication-related osteonecrosis of the jaw (MRONJ) who underwent treatment with bisphosphonates or denosumab. MATERIALS AND METHODS: M1 and M2 macrophage density and expression of interleukin (IL)-6 and IL-10 were assessed on biopsies of mucosal tissues surrounding necrotic bone in 30 MRONJ patients with stages 1-3 and controls. For identification of M1 and M2 macrophages, double CD68/iNOS and CD68/CD206 immunofluorescence staining was conducted, respectively. Computer-assisted immunofluorescence quantification of markers was performed. RESULTS: Early stage 1 MRONJ patients showed a switch toward the M2 phenotype, as indicated by the higher density of M2 macrophages, the decreased M1/M2 ratio, and the upregulation of IL-10. MRONJ patients with advanced stages 2 and 3 showed a shift toward M1-polarized macrophages, as suggested by the higher density of M1 macrophages, the increased M1/M2 ratio, and the overexpression of IL-6. The macrophage density of both M1 and M2 subsets was significantly enhanced in patients receiving bisphosphonates compared with those receiving denosumab. CONCLUSIONS: The M1-M2 macrophage polarization status in mucosal tissues bordering necrotic bone correlates with clinical stage of MRONJ. Patients with early-stage MRONJ show a switch toward M2-polarized macrophages, while MRONJ patients with advanced stage demonstrate a shift toward the M1 phenotype. CLINICAL RELEVANCE: Therapeutic molecules targeting the inflammatory microenvironment via the regulation of either M1 or M2 macrophage polarization may represent a novel strategy for treatment of MRONJ.

Peripheral nerve blocks in the cervical region: from anatomy to ultrasound-guided techniques.

Cervical plexus nerve blocks have been employed in various head and neck operations. Both adequate anaesthesia and analgesia are attained in clinical practice. Nowadays, ultrasound imaging in regional anaesthesia is driven towards a certain objective that dictates high accuracy and safety during the implementation of peripheral nerve blocks. In the cervical region, ultrasound-guided nerve blocks have routinely been conducted only for the past few years and thus only a small number of publications pervade the current literature. Moreover, the sonoanatomy of the neck, the foundation stone of interventional techniques, is very challenging; multiple muscles and fascial layers compose a complex of compartments in a narrow anatomic region, in which local anaesthetics are injected. Therefore, this review intends to deliver new insights into ultrasound-guided peripheral nerve block techniques in the neck. The sonoanatomy of the cervical region, in addition to the cervical plexus, cervical ganglia, superior and recurrent laryngeal nerve blocks are comprehensively discussed.

Surrogates of immunologic cell death (ICD) and chemoradiotherapy outcomes in head and neck squamous cell carcinoma (HNSCC).

OBJECTIVES: Chemoradiation can induce immunogenic (ICD) or tolerogenic cell death. ICD relies on the generation of damage-associated molecular patterns which can stimulate toll-like receptors (TLRs). We sought to determine whether we can predict responses to chemoradiation by measuring surrogate biomarkers of ICD in a cohort of patients with locally advanced (LA) head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: In a cohort of 113 LA HNSCC pts we evaluated expression of TLR4, TLR7 and TLR9 in the EpCAM + circulating tumor cell (CTC) fraction at baseline and after cisplatin chemoradiation. We also quantified changes in chemokines CXCL10, CXCL16 and IL-2R in the serum. RESULTS: Seventy three patients had evaluable specimens. Among cases with biomarker assessment at baseline and post treatment, 36.8% had an increase in CXCL10 levels (p = 0.022), 73.7% had an increase in CXCL16 levels (p = 0.002) and 63.8% had an increase in IL2Ra levels (p = 0.032) with treatment. 52.0% of evaluable cases at baseline and post-treatment had an increase in TLR4 levels (p = 0.996), 42.9% had an increase in TLR7 levels (p = 0.042) and 27.7% had increase in TLR9 levels (p = 0.011) with treatment. CXCL10 levels at baseline were significantly associated with PFS and OS (p = 0.010 and p = 0.032, respectively). CONCLUSIONS: Our results suggest that chemoradiation leads to quantifiable effects in surrogate markers of ICD. These effects may inform trials combining chemoradiation with immune checkpoint inhibitors. In addition, CXCL10 has prognostic effect in pts treated with chemoradiation.

Prognostic value of advanced lung cancer inflammation index in head and neck squamous cell carcinoma.

PURPOSE: The advanced lung cancer inflammation index (ALI) is a useful tool for prediction of outcome in several malignancies. However, to date, its significance in head and neck cancer patients has not been evaluated. METHODS: We retrospectively analyzed data from 93 patients who were diagnosed with head and neck squamous cell carcinoma (HNSCC) and treated with surgical resection and postoperative radiotherapy between 2002 and 2012. The aim of this study was to investigate whether the preoperative ALI is a prognostic indicator for disease-free survival and overall survival in HNSCC patients. RESULTS: A low ALI was significantly associated with a worse 5-year disease-free survival (47.0 vs. 83.5%, p < 0.001), and overall survival (44.4 vs. 73.6%, p = 0.008). Multivariate analysis showed that low ALI was independently associated with disease-free survival (p < 0.001) and overall survival (p = 0.02). CONCLUSION: The ALI could serve as an easily available prognostic indicator for disease-free and overall survival prediction in patients with HNSCC.

Rising incidences of Warthin's tumors may be linked to obesity: a single-institutional experience.

PURPOSE: Recently, there has been an increase in the number of reported Warthin's tumors, but few risk factors have been described for this benign tumor. Yet, smoking is the only evidently identified risk factor. Obesity and the metabolic syndrome are causally linked to or a risk factor for a variety of diseases. Therefore, we analyzed whether metabolic syndrome, including obesity, might influence the incidence of Warthin's tumors. METHODS: In this retrospective study, we evaluated 197 patients with Warthin's tumor. We assessed the tumor size, the body mass index (BMI), comorbidities related to the metabolic syndrome, and cigarette and alcohol consumption. Additionally, we evaluated several blood parameters and their influence. RESULTS: Warthin's tumor patients had a significantly higher BMI in comparison to patients with other benign parotid gland tumors (29.1 versus 26.2, p < 0.0001). The rate of metabolic syndrome-associated comorbidities was higher in Warthin's tumor patients (62.4% versus 35.2%, p < 0.0001). CONCLUSION: Our results might be the first step to recognize obesity and its consequences as a co-driver in the formation of Warthin's tumors. Nevertheless, further studies are requested to validate our results and to answer the question whether obesity or the metabolic syndrome are integrally linked to Warthin's tumors.

Dysregulation of ß-catenin, WISP1 and TCF21 predicts disease-specific survival and primary response against radio(chemo)therapy in patients with locally advanced squamous cell carcinomas of the head and neck.

OBJECTIVE: The objective of this study was to determine the prognostic and predictive impact of ß-catenin, TCF21 and WISP1 expression in patients with squamous cell carcinomas of the head and neck who underwent primary radiotherapy or concomitant chemoradiotherapy. STUDY DESIGN: Prospective cohort study. SETTING: University hospital. PARTICIPANTS: Protein expression profiles of ß-catenin, TCF21, WISP1 and p16 were determined by immunohistochemical analyses in tissue samples of 59 untreated patients. Expression was correlated with different outcome parameters. MAIN OUTCOME MEASURES: Impact of TNM classification, grading, sex, age, gender, type of therapy, response to therapy and p16 status on disease-specific (DSS) and disease-free survival (DFS). RESULTS: Patients with high expression of TCF21 were associated with significantly worse disease-specific survival (P = 0.005). In a multivariable analysis, TCF21 was a significant determinant of disease-specific survival. (HR 3.01; P = 0.036). Conversely, low expression of ß-catenin (P = 0.025) and WISP1 (P = 0.037) revealed a better response to radiotherapy. CONCLUSION: Since data show that TCF21 is a prognostic factor for disease-specific survival and WISP1 and ß-catenin are predictive factors for clinical outcome after definitive radiotherapy, further studies are warranted to prove these preliminary but very promising findings.

Accuracy of soft tissue prediction in surgery-first treatment concept in orthognathic surgery: A prospective study.

PURPOSE: The purpose of this study was to provide a quantitative accuracy assessment of soft tissue predictions generated by a computer-aided maxillofacial planning system in patients undergoing orthognathic surgery following the "surgery-first" treatment. MATERIALS AND METHODS: For this study, we looked at 16 patients with open bite dentofacial-dysmorphosis who underwent orthognathic surgery. Surgeries were planned using conventional sketches and the newly developed computer-assisted SOTIRIOS planning software (developed by the authors). Validation procedures were performed in the following steps: (1) Standardized registration of the pre- and postoperative CT volumes; (2) Automated adjustment of the bone-related preoperative planning to the actual postoperative bony displacement; (3) Simulation of soft tissue changes according to the definitive bony movements; and (4) Calculation of soft tissue differences between the predicted and the actual 6-month postoperative results by distance mapping. RESULTS: The program produced a clinically satisfactory 3D soft tissue prediction, with a mean error of 1.46 mm ± 1.53 mm. The program was suitable for use in virtual surgical planning without technical assistance. CONCLUSION: This study shows that the program is quite accurate, enabling the surgeon to predict the outcome of the soft tissue. This has the potential to promote the routine application of the surgery-first approach in patients suffering from open bite.

Computed tomography accelerates staging in patients with Merkel cell carcinoma.

PURPOSE: No imaging algorithms for diagnostic imaging in patients suffering from Merkel cell carcinoma (MCC) have been established so far and thus staging work-up is challenging. Long presentation-to-treatment intervals determine further treatment course and, consequently, have an impact on clinical outcome in patients with MCC. METHODS: In this retrospective study, diagnostic imaging of 37 MCC patients was analyzed. CT, ultrasound, and PET/PET-CT imaging for primary staging work-up with time frames from patients´ initial presentation and imaging until completion of tumor staging were analyzed. RESULTS: Tumor staging could be completed earlier when (1) less examinations (35 vs. 42 days) were carried out or (2) computed tomography was used as the initial imaging modality (28 vs. 35 days). Furthermore, CT imaging, when used as the initial imaging study, was linked to less follow-up imaging (3 vs. 6). CONCLUSION: Computed tomography as the first-staging imaging technique in MCC patients leads to less follow-up studies and fastest completion of tumor staging.

Expression of 15-lipoxygenase-1 in Merkel cell carcinoma is linked to advanced disease.

BACKGROUND: The purpose of this study was to determine whether the expression of 15-lipoxygenase-1 (ALOX15) in primary tumour specimens predicts lymph node metastasis and subsequently clinical outcome in Merkel cell carcinoma (MCC) patients. METHODS: A retrospective medical chart review of 33 patients was performed between 1994 and 2014. Eleven out of 33 (33%) Patients with primary MCC stages I and II were categorised as group I. Twenty two out of 33 (67%) Patients with regional lymph node metastases and/or distant metastases were defined as group II. All available tumour samples were immunostained for ALOX15, Podoplanin and MCPyV large T-protein antibody. RESULTS: ALOX15 expression was observed in 19/23 (83%) primary tumour samples and in all lymph node metastasis. Primary tumours in patients with stage III and IV disease showed a higher expression rate of ALOX15 compared to patients with early stage disease (11/12 (92%) and 8/11 (73%), respectively). In group I, five patients (45%) were MCPyV positive, whereas in group II, 15 patients (68%) were MCPyV positive. The median lymphatic vessel density in ALOX15 negative group I primary tumour samples was lower compared to the median lymphatic vessel density in ALOX15 positive group I primary tumour probes (2.7 range, 1-4.3 vs 4.7 range, 4.0-7.3). Furthermore, all 17 samples of MCC metastases showed ALOX15 expression with a median lymphatic vessel density (not lymph node metastases) of 5.3 (range 2.0-7.3). CONCLUSION: In the current study, we were able to show ALOX15 expression in the primary MCC sample and the metastasis sample. Based on the findings of the current study, expression rate of ALOX15 in primary MCC and metastases is possibly linked to an increased lymphatic vessel density.

Influence of gender of the teaching staff on students' acceptance of a virtual implant planning course.

Acceptance of new technology is influenced by a number of situational and social factors. So far, only limited data are available on the influence of the teaching staff's gender on the acceptance of virtual dental implant planning by students. This study aimed at assessing the influence of the teaching staff's gender on the acceptance of a virtual implant planning course by male and female undergraduate dental students and their general attitude toward implantology. Two groups of third-year dental students (group 1, 9 males, 22 females; group 2, 12 males, 20 females) attended a virtual dental implant planning course. For the first group the teaching staff was all-male, while the teaching staff was all-female for the second group. After completion of the course the students filled in a technology acceptance questionnaire. An all-female teaching staff led to a degree of technology acceptance that did not differ significantly for male and female students. When the teaching staff was all-male, significant differences for technology acceptance occurred between male and female students. However, male as well as female students attributed the practice of implantology to both genders of dentists, equally, without statistically significant difference independent of the gender of the teaching staff. The more evenly distributed degree of technology acceptance of students of both genders being taught by a female staff is a favorable effect which may be explained by the more egalitarian style of women. Therefore, while feminization in dentistry proceeds, adequate measures should be taken to increase the number of female teachers.