Computer-aided designed 3D-printed polymeric scaffolds for personalized reconstruction of maxillary and mandibular defects: a proof-of-concept study.

PURPOSE: To investigate the potential reconstruction of complex maxillofacial defects using computer-aided design 3D-printed polymeric scaffolds by defining the production process, simulating the surgical procedure, and explore the feasibility and reproducibility of the whole algorithm. METHODS: This a preclinical study to investigate feasibility, reproducibility and efficacy of the reconstruction algorithm proposed. It encompassed 3 phases: (1) scaffold production (CAD and 3D-printing in polylactic acid); (2) surgical simulation on cadaver heads (navigation-guided osteotomies and scaffold fixation); (3) assessment of reconstruction (bone and occlusal morphological conformance, symmetry, and mechanical stress tests). RESULTS: Six cadaver heads were dissected. Six types of defects (3 mandibular and 3 maxillary) with different degree of complexity were tested. In all case the reconstruction algorithm could be successfully completed. Bone morphological conformance was optimal while the occlusal one was slightly higher. Mechanical stress tests were good (mean value, 318.6 and 286.4 N for maxillary and mandibular defects, respectively). CONCLUSIONS: Our reconstructive algorithm was feasible and reproducible in a preclinical setting. Functional and aesthetic outcomes were satisfactory independently of the complexity of the defect.

Regional disease in head and neck cutaneous squamous cell carcinoma: the role of primary tumor characteristics and number of nodal metastases.

PURPOSE: To identify potential risk factors impacting on overall survival (OS) of patients affected by lymph node metastasis from cutaneous squamous cell carcinoma (cSCC) of the head and neck (HN), with special emphasis on primary tumor characteristics and pattern of nodal recurrence (intraparotid and/or cervical). METHODS: A bi-institutional retrospective study on consecutive patients affected by cervical and/or intraparotid NM from HN cSCC and surgically treated with curative intent from May 2010 to January 2020 was conducted. OS was considered the outcome of interest. RESULTS: The study included 89 patients (M:F = 3.4:1; median age, 78 years; range, 22-99). Among the primary tumor characteristics, the most relevant prognostic factors were diameter ≥ 4 cm (hazard ratio [HR] = 2.56, p = 0.010) and depth of infiltration ≥ 6 mm (HR = 3.54, p = 0.027). Cervical NM was associated with worse OS (HR = 2.09, p = 0.016) compared to purely intraparotid NM (5-year OS: 60.9% vs. 28.1%, p = 0.014). At multivariable analysis, age, immunosuppression, pT3-T4 categories and a high burden of nodal disease (> 2 NM) confirmed to be independent risk factors, whereas adjuvant radiotherapy was independently associated with better outcome. CONCLUSION: This study confirms the association of several independent prognosticators related to the patient, primary tumor, and nodal burden status. Patients with cervical NM should be considered at risk for harboring a higher number of metastatic lymph nodes.

Transorbital endoscopic approaches to the skull base: a systematic literature review and anatomical description.

Transorbital endoscopic approaches are increasing in popularity as they provide corridors to reach various areas of the ventral skull base through the orbit. They can be used either alone or in combination with different approaches when dealing with the pathologies of the skull base. The objective of the current study is to evaluate the surgical anatomy of transorbital endoscopic approaches by cadaver dissections as well as providing objective clinical data on their actual employment and morbidity through a systematic review of the current literature. Four cadaveric specimens were dissected, and step-by-step dissection of each endoscopic transorbital approach was performed to identify the main anatomic landmarks and corridors. A systematic review with pooled analysis of the current literature from January 2000 to April 2020 was performed and the related studies were analyzed. Main anatomical landmarks are presented based on the anatomical study and systematic review of the literature. With emphasis on the specific transorbital approach used, indications, surgical technique, and complications are reviewed through the systematic review of 42 studies (19 in vivo and 23 anatomical dissections) including 193 patients. In conclusion, transorbital endoscopic approaches are promising and appear as feasible techniques for the surgical treatment of skull base lesions. Surgical anatomy of transorbital endoscopic approaches can be mastered through knowledge of a number of anatomical landmarks. Based on data available in the literature, transorbital endoscopic approaches represent an important complementary that should be included in the armamentarium of a skull base team.

Matrix for Mucosal Regeneration in Transoral Glossectomy for Squamous Cell Carcinoma: Objective and Subjective Functional Evaluation.

BACKGROUND: Numerous options to manage local reconstruction following transoral partial glossectomy are possible. In this work, we present our experience using a matrix for mucosal regeneration, Integra®, after transoral resections of squamous cell carcinoma of the oral tongue. METHODS: A retrospective analysis of patients treated for tongue carcinoma and reconstruction with Integra®, from September 2017 to September 2022. Functional outcomes were evaluated by measuring swallowing and speech abilities, tongue motility, and subjective quality of life. RESULTS: The series accounts for 13 consecutive patients, staged from Tis to T3, no positive resection margins were found, average defect size was 17.8 cm2. The average histologically measured depth of invasion was 4.1 mm (range 2-12 mm), and no recurrences were observed during follow-up. All patients maintained excellent swallowing function, the average number of recognized words by an external listener during a phone call was 70.5 out of 75, the lingual motility test was good (a mean score of 4.5 out of 6 movements correctly executed) and subjective questionnaires results were optimal. Less satisfying functional results were recorded in elderly patients receiving a wider surgical resection. CONCLUSIONS: This reconstructive technique for allows obtaining optimal healing and functional outcomes in patients with tumors suitable for transoral glossectomy.

Central Compartment Neck Dissection in Laryngeal and Hypopharyngeal Squamous Cell Carcinoma: Clinical Considerations.

Metastatic lymph node involvement represents the most relevant prognostic factor in head and neck squamous cell carcinomas (HNSCCs), invariably affecting overall survival, disease-specific survival, and relapse-free survival. Among HNSCCs, laryngeal and hypopharyngeal cancers are known to be at highest risk to metastasize to the central neck compartment (CNC). However, prevalence and prognostic implications related to the CNC involvement are not well defined yet, and controversies still exist regarding the occult metastasis rate. Guidelines for the management of CNC in laryngeal and hypopharyngeal cancers are vague, resulting in highly variable selection criteria for the central neck dissection among different surgeons and institutions. With this review, the authors intend to reappraise the existing data related to the involvement of CNC in laryngeal and hypopharyngeal malignancies, in the attempt to define the principles of management while highlighting the debated aspects that are lacking in evidence and consensus. Furthermore, as definition and boundaries of the CNC have changed over the years, an up-to-date anatomical-surgical description of the CNC is provided.

Ultrasound-guided wire localisation: a GPS for hidden head and neck tumours? A case series.

Objectives: Ultrasound-guided wire (USGW) localisation for small non-palpable tumours before a revision head and neck surgery is an attractive pre-operative option to facilitate tumour identification and decrease potential complications. We describe five cases of pre-operative USGW localisation of non-palpable head and neck lesions to facilitate surgical localisation and resection. Methods: All patients undergoing pre-operative USGW localisation for non-palpable tumours of the head and neck region at London Health and Sciences Center, London, Ontario, Canada, were included. All the USGW localisations were performed by the same interventional radiologist, and the surgeries were performed by fellowship trained head and neck surgeons. Results: Five patients were included. All patients were undergoing revision surgery for recurrent or persistent disease. All successfully underwent a pre-operative USGW localisation of the non-palpable lesion before revision surgery. All lesions were localised intra-operatively with no peri-operative complications. Conclusions: USGW localisation is a safe and effective pre-operative technique for the identification of small non-palpable head and neck tumours.

Versatility of the subscapular system of flaps in head and neck oncologic reconstruction.

PURPOSE OF REVIEW: This review analyzes the different ways of applying the subscapular system of flaps (SSSF) as a convenient and versatile solution for a large variety of head and neck oncologic defects. RECENT FINDINGS: The ventral approach permits safe and efficient harvest of various chimeric SSSF in a supine position, thus allowing simultaneous flap preparation and tumor ablation. Conformational studies have revealed how similar the tip of the scapula is to the hard palate in terms of dimensions, shape, and conformation. This has led to favor horizontal placement of the scapular tip for palate reconstruction in most instances, addressing the vertical extension of the postmaxillectomy defect using denuded bony grafts surrounded by well vascularized chimeric muscular components. SUMMARY: The SSSF possesses an unparalleled versatility to efficiently address small-medium sized soft tissue defects up to vast and complex composite resections. The chimeric components of these flaps benefit from a considerable independency provided by the length of the named arteries arising from the thoracodorsal pedicle, offering a high degree of freedom to accomplish the required in-setting. This reconstructive option should be implemented in every head and neck surgical team and offered to suitable patients.

Does Reorganization of Clinicopathological Information Improve Prognostic Stratification and Prediction of Chemoradiosensitivity in Sinonasal Carcinomas? A Retrospective Study on 145 Patients.

Background: The classification of sinonasal carcinomas (SNCs) is a conundrum. Consequently, prognosis and prediction of response to non-surgical treatment are often unreliable. The availability of prognostic and predictive measures is an unmet need, and the first logical source of information to be investigated is represented by the clinicopathological features of the disease. The hypothesis of the study was that clinicopathological information on SNC could be exploited to better predict prognosis and chemoradiosensitivity. Methods: All patients affected by SNC who received curative treatment, including surgery, at the Unit of Otorhinolaryngology-Head and Neck Surgery of the University of Brescia between October 1998 and February 2019 were included in the analysis. The institutional series was reviewed and a survival analysis was performed. Machine learning and multivariable statistical methods were employed to develop, analyze, and test 3 experimental classifications (classification #1, based on cytomorphological, histomorphological, and differentiation information; classification #2, based on differentiation information; and classification #3, based on locoregional extension) of SNC, based on the inherent clinicopathological information. The association of experimental classifications with prognosis and chemoradiosensitivity was tested. Results: The study included 145 patients. From a prognostic standpoint, the machine learning-generated classification of SNC provided better prediction than the current World Health Organization classification. However, the prediction of the chemoradiosensitivity of SNC was not achievable. Conclusions: Reorganization of clinicopathological information, with special reference to those related to tumor differentiation, can improve the reliability of prognosis of SNC. Prediction of chemoradiosensitivity remains an unmet need and further research is required.

Projected cutting guides using an augmented reality system to improve surgical margins in maxillectomies: A preclinical study.

BACKGROUND: Positive margins have been reported up to 80% in advanced maxillary cancers. Intraoperative navigation (IN) aims to improve margins, but provides a two-dimensional view of a registered instrument without anticipating any cutting directions, and the information is displayed in monitors outside surgical field. Augmented Reality (AR) can delineate margins while addressing the gaze-toggling drawback of IN. In a preclinical setting, we implemented preoperative-planned osteotomies needed for maxillectomies and projected this information on the surgical field using AR. We aimed to improve negative margin rates while retaining the benefits of AR. METHODS: Five maxillary tumor models were built. Five fellowship-trained surgeons completed virtual unguided and AR-guided maxillectomies. Comparisons in terms of intratumoral cuts, close, adequate, and excessive distances from the tumor were performed. Differences between "ideal" cutting-plan and the AR-guided virtual osteotomies was obtained. Workload questionnaires to evaluate the technology were completed. RESULTS: 115 virtual osteotomies were analyzed. Intra-tumoral and "close" margins were lower for the AR-assisted osteotomies (0.0% vs 1.9% p < 0.0001 and 0.8% vs 7.9% p < 0.0001). Proportion of "adequate" margins were higher in the AR simulations (25.3% vs 18.6%, p = 0.018). The AR osteotomies had high similarity with the pre-planned with interclass correlation index close to 1 in "adequate" margins 0.893 (95% CI: 0.804-0.949). Workload scores were better for AR-guided simulations for the domains of mental demand, performance, effort and frustration. CONCLUSION: The projector-based AR method improved margin delineation, and preoperative planning was accurately translated to the simulations. Clinical translation will aim to consolidate our preclinical findings to improve outcomes.

Development of a cadaveric head and neck cancer model and three-dimensional analysis of margins in surgical navigation-aided ablations.

INTRODUCTION: The adequacy of the surgical resection is the main controllable variable that is in the hands of the surgical team. There exists an unmet need to increase the rate of negative margins, particularly in cancers invading the craniofacial area. The study aimed 1) at developing a gross tumor model to be utilized for research, educational, and training purposes and 2) establishing the 3-dimensional relationship between the outer surface of the surgical specimen and tumor surface and test the effect of guiding ablations on cadavers with surgical navigation (SN). MATERIAL AND METHODS: Seven cadaver heads were employed to create 24 craniofacial tumor models. Simulation of tumor resections was performed by 8 surgeons. Fourteen and 10 resections were performed with and without SN-guidance, respectively. Gross specimens underwent computed tomography and 3-dimensional analysis through dedicated software. Task load was assessed through a validated questionnaire. Tumor model reliability was studied based on visual analogue scale rate by surgeons and radiologists. RESULTS: SN reduced the rate of margin involvement, particularly by decreasing the percentage of the gross specimen outer surface involvement in areas uncovered by normal bony structures. The workload of SN-aided ablations was found to be medium-to-somewhat-high. Tumor model reliability was deemed satisfactory except for the extension to bony structures. CONCLUSIONS: A gross tumor model for head and neck cancers involving the craniofacial area was developed and resulted satisfactorily reliable from both a surgical and radiologic standpoint. SN reduced the rate of margin involvement, particularly by improving delineation of bone-uncovered areas.

Patterns of recurrences in sinonasal cancers undergoing an endoscopic surgery-based treatment: Results of the MUSES* on 940 patients: *MUlti-institutional collaborative Study on Endoscopically treated Sinonasal cancers.

OBJECTIVES: The improvements in survival with expansion of the survivors' population, along with evolution of endoscopically-based treatment modalities, have contributed to emphasize the clinical relevance of recurrences in sinonasal cancers. However, at present, literature is scant regarding the pattern of recurrences and the therapeutic strategies available to manage long survivors who experienced single or multiple failures. The aim of the present study was to analyze sinonasal cancers recurrences to provide data regarding rates and patterns of relapse, predictors of failure and prognostic impact of the recurrence. MATERIALS AND METHODS: All patients receiving multimodal treatments including endoscopic surgery between 1995 and 2021 in three European referral centers were included. Statistical analysis of survival was performed through univariable, multivariable and unidirectional multistate models. Survival after recurrence analysis was implemented for patients experiencing at least one recurrence. RESULTS: The 5- and 10-year recurrence free survival rates were 34.1% and 38.4% for the whole population. With a mean follow-up time of 60 months, a global recurrence rate of 32.9% was observed. The 5- and 10-year survival after recurrence rates were 27.2% and 21.7%, respectively. Incidence and rates of recurrences were significantly associated with histology subtypes. CONCLUSION: This study provides valuable oncologic outcomes regarding a large homogenous cohort of patients affected by sinonasal malignances treated within a multimodal framework, emphasizing the strong correlation of histologic type with prognosis, as well as with pattern of recurrences.

The MUSES∗: a prognostic study on 1360 patients with sinonasal cancer undergoing endoscopic surgery-based treatment: ∗MUlti-institutional collaborative Study on Endoscopically treated Sinonasal cancers.

BACKGROUND: Over the last 2 decades, transnasal endoscopic surgery (TES) has become the most frequently employed surgical technique to treat sinonasal malignancies. The rarity and heterogeneity of sinonasal cancers have hampered large non-population-based analyses. METHODOLOGY: All patients receiving TES-including treatment between 1995 and 2021 in 5 referral hospitals were included. A prognostic study was performed, and multivariable models were transformed into nomograms. Training and validation sets were based on results from 3 European and 2 non-European centres, respectively. RESULTS: The training and validation set included 940 and 420 patients, respectively. The mean age at surgery, primary-versus-recurrent presentation, histology distribution, type of surgery, T category and type of adjuvant treatment were differently distributed in the training and validation set. In the training set, 5-year overall survival and recurrence-free survival with a 95%-confidence interval were 72.7% (69.5-76.0%) and 66.4% (63.1-69.8%), respectively, significantly varying with histology. At multivariable analyses, age, gender, previous treatment, the extent of resection on the cranial, lateral and posterolateral axes, grade/subtype, T category, nodal status, margin status and adjuvant treatment were all associated with different prognostic outcomes, displaying a heterogeneous significance and effect size according to histology. The internal and external validation of nomograms was satisfactory (optimism-corrected C-index >0.7 and cumulative area under curve >0.7) for all histologies but mucosal melanoma. CONCLUSIONS: Outcomes of TES-based treatment of sinonasal cancers vary substantially with histology. This large, non-population-based study provides benchmark data on the prognosis of sinonasal cancers that are deemed suitable for treatment including TES.

Bioengineering for head and neck reconstruction: the role of customized flaps.

PURPOSE OF REVIEW: The purpose of this review is to provide the reader with an overview of the present and future applications of bioengineering for head and neck reconstruction, ranging from the application of Computed Assisted Surgery (CAS) to the most recent advances in 3D printing and tissue engineering. RECENT FINDINGS: The use of CAS in head and neck reconstruction has been demonstrated to provide shorter surgical times, improved reconstructive accuracy of bone reconstruction, and achieves better alignment of bone segments in osteotomized reconstructions. Beyond its classical application in bone reconstructions, CAS has demonstrated reliability in the planning and harvesting of soft tissue flaps. To date, literature regarding bioengineering for head and neck reconstruction is mainly focused on in-vitro and animal model experiments; however, some pioneering reports on human patients suggest the potential feasibility of this technology. SUMMARY: Bioengineering is anticipated to play a key role in the future development of customized flaps for head and neck reconstruction. These technologies are particularly appealing as a new technology to address certain unsolved challenges in head and neck reconstruction.

Objective evaluation of orbito-zygomatic reconstruction with scapular tip free flaps to restore facial projection and orbital volume.

BACKGROUND: Restoring anatomical contour and position of the malar eminence and orbital rim following ablative mid-face procedures is critical in maintaining facial contour and orbit position. OBJECTIVE: To report our reconstructive approach using the scapular tip free-flap (STFF) for orbito-zygomatic defects, evaluating contour and overall shape restoration. METHODS: The study included 2 series: a clinical cohort of 15 consecutive patients who underwent an orbito-zygomatic reconstruction with a STFF and a cohort of 10 patients who had CT scan imaging but did not have orbito-zygomatic surgical resection or reconstruction. Using a 3D software, overall conformance (OC) and contour conformance (CC) with respect to the mirrored contralateral (clinical cohort) or native zygoma (preclinical cohort) were analyzed. Postoperative orbital volumes were also measured in the clinical cohort. Mean, median, root-mean-square (RMS), minimum and maximum measurements were obtained both for OC and CC. Conformance values of clinical and preclinical cohort were compared to objectively evaluate the quality of reconstruction in terms of orbito-zygomatic framework restoration (Mann-Whitney test). RESULTS: All measurements for OC and CC between scapular tip and the zygoma showed no differences, both on the clinical (RMS: OC 3.29 mm vs CC 3.32 mm -p = NS-) and preclinical (RMS: OC 2.03 mm and CC 2.31 mm -p = NS-) cohorts. Moreover, there were no differences in post-operative orbital volumes in the clinical cohort. Clinical outcomes of the case-series are also reported. CONCLUSION: The STFF is highly effective in restoring facial projection and orbital volume in orbito-zygomatic reconstruction.

A new landmark for lingual artery identification during transoral surgery: Anatomic-radiologic study.

BACKGROUND: A landmark for the identification of the lingual artery (LA) through a transoral perspective can provide surgeons with an easy method to prevent and manage intraoperative bleeding during transoral approach to the base of tongue (BOT). METHODS: Thirteen tongue and five head and neck specimens were dissected to identify and assess the reliability of the lingual point (LP) as a new landmark for the LA at BOT. The pathway of 42 LAs was radiologically evaluated; axial depth and vertical offset were measured for each LA. RESULTS: Dissection study: a description of LP is provided; the LA was easily identified in all specimens (36/36 sides) using LP as a landmark. Radiologic study: the mean depth of the LA was 4.2 mm, the mean vertical offset was 1.3 mm. CONCLUSIONS: LP is a simple and reliable landmark for identification of the LA, potentially helping surgeons to prevent and manage intraoperative bleeding.

Genome-wide study of salivary miRNAs identifies miR-423-5p as promising diagnostic and prognostic biomarker in oral squamous cell carcinoma.

Survival rates of oral squamous cell carcinoma (OSCC) remained substantially unchanged over the last decades; thus, additional prognostic tools are strongly needed. Salivary miRNAs have emerged as excellent non-invasive cancer biomarker candidates, but their association with OSCC prognosis has not been investigated yet. In this study, we analyzed global salivary miRNA expression in OSCC patients and healthy controls, with the aim to define its diagnostic and prognostic potential. Methods: Saliva was collected from patients with newly diagnosed untreated primary OSCC and healthy controls. Global profiling of salivary miRNAs was carried out through a microarray approach, while signature validation was performed by quantitative real-time PCR (RT-qPCR). A stringent statistical approach for microarray and RT-qPCR data normalization was applied. The diagnostic performance of miRNAs and their correlation with OSCC prognosis were comprehensively analyzed. Results: In total, 25 miRNAs emerged as differentially expressed between OSCC patients and healthy controls and, among them, seven were significantly associated with disease-free survival (DFS). miR-106b-5p, miR-423-5p and miR-193b-3p were expressed at high levels in saliva of OSCC patients and their combination displays the best diagnostic performance (ROC - AUC = 0.98). Moreover, high expression of miR-423-5p was an independent predictor of poor DFS, when included in multivariate survival analysis with the number of positive lymph nodes - the only significant clinical prognosticator. Finally, we observed a significant decrease in miR-423-5p expression in matched post-operative saliva samples, suggesting its potential cancer-specific origin. Conclusion: Salivary miRNAs identified in our cohort of patients show to be accurate in OSCC detection and to effectively stratify patients according to their likelihood of relapse. These results, if validated in an independent set of patients, could be particularly promising for screening/follow-up of high-risk populations and useful for preoperative prognostic assessment.

Applications of intraoperative angiography in head and neck reconstruction.

OBJECTIVE: Laser-assisted angiography with indocyanine green (LAIG) allows objective intraoperative evaluation of tissue vascularity. We endeavored to describe our experience with this technique in the head and neck region. METHODS: A retrospective review from February 2016 till October 2018 was conducted. We included patients who underwent head and neck procedures in which LAIG was employed. The main outcome was postoperative wound complications. We analysed the influence of LAIG results in intraoperative decision-making process. RESULTS: Nineteen patients were included, and follow-up was for at least 6 months. LAIG was employed in 11 local flaps, 9 free flaps and 6 cases of pharyngeal closure during total laryngectomies. Wound complications occurred in two cases with distal tip flap necrosis. LAIG findings resulted in changes in decision making intraoperatively in 84% of procedures, which consisted in trimming poorly perfused tissues. There were no pharyngocutaneous fistulas. CONCLUSIONS: This represents a descriptive report on the use of LAIG on diverse head and neck reconstruction cases, with important impact on the decision-making process. A low number of postoperative wound complications were observed.

Early Postoperative Magnetic Resonance in the Diagnosis of Persistent Juvenile Angiofibroma.

OBJECTIVES/HYPOTHESIS: Despite improvements in the treatment of juvenile angiofibroma (JA), the rate of persistence (pJA) is still not negligible. In the present study, we assessed the value of early postoperative magnetic resonance imaging (MRI) in depicting unintentional pJAs and designed a MRI-driven decisional flow-chart for pJA management and follow-up. STUDY DESIGN: Observational study. METHODS: Patients undergoing early postoperative MRI after endoscopic resection of JA in the Unit of Otorhinolaryngology - ASST Spedali Civili, University of Brescia from 2007 to 2017 were enrolled. MRI was defined as negative or positive based on defined radiological criteria. The diagnostic performance of MRI was evaluated. RESULTS: The analysis included 26 patients, with a mean age of 16.5 years (range, 11-25). Early MRI was negative for pJA in 21 (80.8%) patients and positive in five (19.2%). No patient with a negative finding was found positive at subsequent follow-up MRIs. The accuracy of a positive finding was confirmed by pathologic examination (three cases) or follow-up MRIs (two cases). The diagnostic performance of MRI was excellent with sensitivity and specificity of 100%. An MRI-driven flow-chart for pJA management and follow-up was designed. CONCLUSIONS: Early postoperative MRI demonstrated a high diagnostic accuracy in the detection of unintentional pJA. Our MRI-driven strategy and decisional flow-chart could aid in the decision-making process in the management of pJA and definition of postoperative surveillance. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E2436-E2441, 2021.