3D Specimen Scanning and Mapping in Musculoskeletal Oncology: A Feasibility Study.

BACKGROUND: Surgical resection is the primary treatment for bone and soft tissue tumors. Negative margin status is a key factor in prognosis. Given the three-dimensional (3D) anatomic complexity of musculoskeletal tumor specimens, communication of margin results between surgeons and pathologists is challenging. We sought to perform ex vivo 3D scanning of musculoskeletal oncology specimens to enhance communication between surgeons and pathologists. METHODS: Immediately after surgical resection, 3D scanning of the fresh specimen is performed prior to frozen section analysis. During pathologic grossing, whether frozen or permanent, margin sampling sites are annotated on the virtual 3D model using computer-aided design (CAD) software. RESULTS: 3D scanning was performed in seven cases (six soft tissue, one bone), with specimen mapping on six cases. Intraoperative 3D scanning and mapping was performed in one case in which the location of margin sampling was shown virtually in real-time to the operating surgeon to help achieve a negative margin. In six cases, the 3D model was used to communicate final permanent section analysis. Soft tissue, cartilage, and bone (including lytic lesions within bone) showed acceptable resolution. CONCLUSIONS: Virtual 3D scanning and specimen mapping is feasible and may allow for enhanced documentation and communication. This protocol provides useful information for anatomically complex musculoskeletal tumor specimens. Future studies will evaluate the effect of the protocol on positive margin rates, likelihood that a re-resection contains additional malignancy, and exploration of targeted adjuvant radiation protocols using a patient-specific 3D specimen map.

Augmented-Reality Surgery to Guide Head and Neck Cancer Re-resection: A Feasibility and Accuracy Study.

BACKGROUND: Given the complex three-dimensional (3D) anatomy of head and neck cancer specimens, head and neck surgeons often have difficulty relocating the site of an initial positive margin to perform re-resection. This cadaveric study aimed to determine the feasibility and accuracy of augmented reality surgery to guide head and neck cancer re-resections. METHODS: This study investigated three cadaveric specimens. The head and neck resection specimen was 3D scanned and exported to the HoloLens augmented reality environment. The surgeon manually aligned the 3D specimen hologram into the resection bed. Accuracy of manual alignment and time intervals throughout the protocol were recorded. RESULTS: The 20 head and neck cancer resections performed in this study included 13 cutaneous and 7 oral cavity resections. The mean relocation error was 4 mm (range, 1-15 mm) with a standard deviation of 3.9 mm. The mean overall protocol time, from the start of 3D scanning to alignment into the resection bed, was 25.3 ± 8.9 min (range, 13.2-43.2 min). Relocation error did not differ significantly when stratified by greatest dimension of the specimen. The mean relocation error of complex oral cavity composite specimens (maxillectomy and mandibulectomy) differed significantly from that of all the other specimen types (10.7 vs 2.8; p < 0.01). CONCLUSIONS: This cadaveric study demonstrated the feasibility and accuracy of augmented reality to guide re-resection of initial positive margins in head and neck cancer surgery.

Genome-wide association mapping of ethanol sensitivity in the Diversity Outbred mouse population.

BACKGROUND: A strong predictor for the development of alcohol use disorder (AUD) is altered sensitivity to the intoxicating effects of alcohol. Individual differences in the initial sensitivity to alcohol are controlled in part by genetic factors. Mice offer a powerful tool to elucidate the genetic basis of behavioral and physiological traits relevant to AUD, but conventional experimental crosses have only been able to identify large chromosomal regions rather than specific genes. Genetically diverse, highly recombinant mouse populations make it possible to observe a wider range of phenotypic variation, offer greater mapping precision, and thus increase the potential for efficient gene identification. METHODS: We have taken advantage of the Diversity Outbred (DO) mouse population to identify and precisely map quantitative trait loci (QTL) associated with ethanol sensitivity. We phenotyped 798 male J:DO mice for three measures of ethanol sensitivity: ataxia, hypothermia, and loss of the righting response. We used high-density MegaMUGA and GigaMUGA to obtain genotypes ranging from 77,808 to 143,259 SNPs. We also performed RNA sequencing in striatum to map expression QTLs and identify gene expression-trait correlations. We then applied a systems genetic strategy to identify narrow QTLs and construct the network of correlations that exists between DNA sequence, gene expression values, and ethanol-related phenotypes to prioritize our list of positional candidate genes. RESULTS: We observed large amounts of phenotypic variation with the DO population and identified suggestive and significant QTLs associated with ethanol sensitivity on chromosomes 1, 2, and 16. The implicated regions were narrow (4.5-6.9 Mb in size) and each QTL explained ~4-5% of the variance. CONCLUSIONS: Our results can be used to identify alleles that contribute to AUD in humans, elucidate causative biological mechanisms, or assist in the development of novel therapeutic interventions.

Osteoradionecrosis of the hyoid bone complicated by pharyngocutaneous fistula: A case report and literature review.

BACKGROUND: Osteoradionecrosis (ORN) is a well-known complication following irradiation of head and neck malignancies. ORN commonly occurs in the mandible but is rarely reported in the hyoid bone. CASE PRESENTATION: A 76-year-old female with a history of oropharyngeal squamous cell carcinoma presented with pharyngocutaneous fistula 14 years after primary chemoradiation. Imaging showed necrosis of the hyoid bone. She underwent excision of the hyoid to rule out malignancy. Pathology was negative for carcinoma, but did show extensive fragmentation and bony necrosis consistent with ORN. The patient's clinical course, surgical treatment, and management considerations are discussed here. CONCLUSIONS: Hyoid ORN should remain in the differential during diagnostic workup of previously irradiated head and neck cancer patients. The presentation of a pharyngocutaneous fistula should prompt workup to rule out malignancy before assigning a diagnosis of ORN.

Genome-wide association for testis weight in the diversity outbred mouse population.

Testis weight is a genetically mediated trait associated with reproductive efficiency across numerous species. We sought to evaluate the genetically diverse, highly recombinant Diversity Outbred (DO) mouse population as a tool to identify and map quantitative trait loci (QTLs) associated with testis weight. Testis weights were recorded for 502 male DO mice and the mice were genotyped on the GIGAMuga array at ~ 143,000 SNPs. We performed a genome-wide association analysis and identified one significant and two suggestive QTLs associated with testis weight. Using bioinformatic approaches, we developed a list of candidate genes and identified those with known roles in testicular size and development. Candidates of particular interest include the RNA demethylase gene Alkbh5, the cyclin-dependent kinase inhibitor gene Cdkn2c, the dynein axonemal heavy chain gene Dnah11, the phospholipase D gene Pld6, the trans-acting transcription factor gene Sp4, and the spermatogenesis-associated gene Spata6, each of which has a human ortholog. Our results demonstrate the utility of DO mice in high-resolution genetic mapping of complex traits, enabling us to identify developmentally important genes in adult mice. Understanding how genetic variation in these genes influence testis weight could aid in the understanding of mechanisms of mammalian reproductive function.

Septic arthritis of the sternoclavicular joint: A unique late complication after tracheostomy.

BACKGROUND: Septic arthritis of the sternoclavicular joint is a rare infection associated with significant morbidity and mortality. Several risk factors for septic arthritis have been reported in the literature ranging from immunodeficiency to intravenous drug use. CASE PRESENTATION: A 63-year-old male previously treated for synchronous squamous cell carcinomas of the epiglottis and floor of mouth presented with tenderness and swelling of the sternoclavicular joint two months after tracheostomy decannulation. Computed tomography and bone scans confirmed the diagnosis of septic arthritis of the sternoclavicular joint. The patient's clinical course, surgical treatment, and management considerations are discussed here. CONCLUSION: Septic arthritis of the SCJ is a rare but serious infection. Once diagnosed, septic arthritis of the SCJ should be promptly treated to prevent further morbidity and mortality.

Virtual 3D Specimen Mapping in Head & Neck Oncologic Surgery.

OBJECTIVES: Virtual 3D specimen mapping of oncologic surgical specimens provides a visual record of the specimen and margin sampling sites which can be utilized in a variety of cancer care settings. Our objective was to perform a retrospective review of head and neck surgical oncology cases where the specimen was mapped post-operatively and to evaluate the utility of these 3D specimen maps amongst the multidisciplinary cancer care team. METHODS: A retrospective review of our 3D specimen model biorepository was performed. Surgical specimens were 3D scanned and then graphically annotated (or "mapped") during routine pathologic processing. The resulting 3D specimen maps were distributed to the multidisciplinary oncologic care team. Final margin status and any use of the 3D specimen maps were recorded. RESULTS: A total of 28 cases were included. Virtual 3D specimen maps were utilized by the cancer care team in 8 cases (29%), including 2 positive margin cases, 2 close margin cases, and 4 indeterminate margin cases. 3D specimen maps were used to visualize positive margin sites for pathologist-surgeon communication as a visual reference during tumor board discussions and to inform radiation treatment planning. CONCLUSION: Post-operative virtual 3D specimen mapping of oncologic specimens creates a permanent visual record of the specimen and the margins sampled and may serve as a beneficial tool for communication amongst the multidisciplinary cancer care team. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:191-197, 2024.

Enhanced Communication of Tumor Margins Using 3D Scanning and Mapping.

After oncologic resection of malignant tumors, specimens are sent to pathology for processing to determine the surgical margin status. These results are communicated in the form of a written pathology report. The current standard-of-care pathology report provides a written description of the specimen and the sites of margin sampling without any visual representation of the resected tissue. The specimen itself is typically destroyed during sectioning and analysis. This often leads to challenging communication between pathologists and surgeons when the final pathology report is confirmed. Furthermore, surgeons and pathologists are the only members of the multidisciplinary cancer care team to visualize the resected cancer specimen. We have developed a 3D scanning and specimen mapping protocol to address this unmet need. Computer-aided design (CAD) software is used to annotate the virtual specimen clearly showing sites of inking and margin sampling. This map can be utilized by various members of the multidisciplinary cancer care team.

Ex vivo 3D scanning and specimen mapping in anatomic pathology.

Structured light three-dimensional (3D) scanning is a ubiquitous mainstay of object inspection and quality control in industrial manufacturing, and has recently been integrated into various medical disciplines. Photorealistic 3D scans can readily be acquired from fresh or formalin-fixed tissue and have potential for use within anatomic pathology (AP) in a variety of scenarios, ranging from direct clinical care to documentation and education. Methods for scanning and post-processing of fresh surgical specimens rely on relatively low-cost and technically simple procedures. Here, we demonstrate potential use of 3D scanning in surgical pathology in the form of a mixed media pathology report with a novel post-scan virtual inking and marking technique to precisely demarcate areas of tissue sectioning and details of final tumor and margin status. We display a sample mixed-media pathology report (3D specimen map) which integrates 3D and conventional pathology reporting methods. Finally, we describe the potential utility of 3D specimen modeling in both didactic and experiential teaching of gross pathology lab procedures.

Enhanced Intraoperative Communication of Tumor Margins Using 3D Scanning and Mapping: The Computer-Aided Design Margin.

We have implemented a novel intraoperative communication system for head and neck surgical pathology using 3D scanning technology and computer-aided design (CAD) software. Here, we highlight our CAD margin protocol, in which we 3D scan head and neck oncologic surgical specimens and map frozen section results. This enhances the communication of margin status between surgeons and pathologists and delivers visual anatomic guidance for re-resection when needed. Laryngoscope, 133:1914-1918, 2023.

Frozen Section Analysis in Head and Neck Surgical Pathology: A Narrative Review of the Past, Present, and Future of Intraoperative Pathologic Consultation.

Frozen section has remained the diagnostic gold standard for intraoperative pathological evaluation of surgical margins for head and neck specimens. While achieving tumor-free margins is of utmost importance to all head and neck surgeons, in practice, there are numerous debates and a lack of standardization for the role and method of intraoperative pathologic consultation. This review serves as a summary guide to the historical and contemporary practice of frozen section analysis and margin mapping in head and neck cancer. In addition, this review discusses current challenges in head and neck surgical pathology, and introduces 3D scanning as a groundbreaking technology to bypass many of the pitfalls in the current frozen section workflow. The ultimate goal for all head and neck pathologists and surgeons should be to modernize practices and take advantage of new technology, such as virtual 3D specimen mapping techniques, that improves the workflow for intraoperative frozen section analysis.

Mapping Genetic Susceptibility to Stenosis in the Proximal Airway.

OBJECTIVES: Recent translational scientific efforts in subglottic stenosis (SGS) support a disease model where epithelial alterations facilitate microbiome displacement, dysregulated immune activation, and localized fibrosis. Yet despite recent advances, the genetic basis of SGS remains poorly understood. We sought to identify candidate risk genes associated with an SGS phenotype, investigate their biological function, and identify the cell types enriched for their expression. METHODS: The Online Mendelian Inheritance in Man (OMIM) database was queried for single gene variants associated with an SGS phenotype. The functional intersections and molecular roles of the identified genes were explored using pathway enrichment analysis (PEA) computational methods. Cellular localization of the candidate risk genes was measured via transcriptional quantification in an established single cell RNA sequencing (scRNA-seq) atlas of the proximal airway. RESULTS: Twenty genes associated with SGS phenotype were identified. PEA resulted in 24 significantly enriched terms including "cellular response to TGF-ß," "epithelial-to-mesenchymal transition," and "adherens junctions." Mapping the 20 candidate risk genes to the scRNA-seq atlas found 3 (15%) genes were enriched in epithelial cells, 3 (15%) in fibroblasts, and 3 (15%) in endothelial cells. 11 (55%) genes were expressed ubiquitously among tissue types. Interestingly, immune cells were not significantly enriched for candidate risk genes. CONCLUSION: We identify and provide biologic context for 20 genes associated with fibrotic disease of the proximal airway and form the foundation for future detailed genetic study. LEVEL OF EVIDENCE: N/A Laryngoscope, 133:3049-3056, 2023.

The computer-aided design margin: Ex vivo 3D specimen mapping to improve communication between surgeons and pathologists.

BACKGROUND: Numerous challenges exist in determining surgical margin status. Communication between surgeons and pathologists is crucial for specimen orientation and accurate margin assessment. METHODS: A prospective study to determine feasibility of incorporating three-dimensional (3D) scanning into surgical pathology workflow was performed. A structured-light 3D scanner captured the photorealistic surface topography of fresh surgical specimens. Computer-aided design (CAD) software was used to document sites of margin sampling and sectioning. Surveys were distributed among faculty and staff stakeholders to assess feasibility. RESULTS: A series of 40 cases were 3D-scanned. Median image acquisition time was 8 min. The majority of respondents agreed that the experimental 3D system helped achieve clearer communication. 3D specimen maps assisted in the communication of a focally positive or close margin in 4 of 17 cases. CONCLUSIONS: Routine 3D scanning and specimen mapping is feasible and represents an innovative approach to intraoperative and final pathology documentation, margin analysis, and surgeon-pathologist communication.

Multimodal Virtual 3D Representation of a Giant Cell Tumor of the Thyroid Cartilage.

Virtual three-dimensional (3D) scanning of pathologic specimens may allow for improved communication between the surgeon and pathologist, as well as enhanced patient counseling and engagement. We report the rare case of a giant cell tumor of the thyroid cartilage and present a multimodal 3D representation. Preoperative 3D printing of the anatomic structures from cross-sectional imaging, as well as novel ex vivo 3D scanning of the fresh pathologic specimen for virtual 3D specimen mapping, was performed.

Oral squamous carcinoma: Aggressive tumor pattern of invasion predicts direct mandible invasion.

BACKGROUND: Aggressive histologic worst pattern of invasion (WPOI) in surrounding soft tissue has been shown to be predictive of higher local recurrence and poorer survival in oral cavity squamous cell carcinoma (OCSCC) patients. This study investigates whether aggressive WPOI can predict the mandibular invasion phenotype. METHODS: Patients consecutively diagnosed with OCSCC undergoing a mandibulectomy (marginal or segmental) between 2013 and 2018 were reviewed. Senior physicians re-reviewed radiologic scans and pathologic slides of 44 cases. RESULTS: Aggressive WPOI (WPOI-4, 5) is significantly associated with infiltrative bone invasion. Non-aggressive WPOI (WPOI-1, 2, 3) is significantly associated with the absence of bone invasion. CONCLUSIONS: WPOI has become a useful tool that further characterizes the biologic behavior of OCSCC. Potentially, planned surgery may escalate from a marginal to segmental mandibulectomy based on aggressive WPOI for patients with radiographically uncertain cortical status. Further studies are needed to validate the relationship between OCSCC WPOI and mandible status.

Reconstructive and prosthodontic outcomes after multiple palatomaxillary reconstructions.

OBJECTIVE: A subset of patients who undergo major palatomaxillary reconstruction do not initially achieve their intended oncologic and/or reconstructive goals and require additional surgery. We aim to detail the unique management considerations in this patient population. METHODS: We performed a retrospective review of patients who underwent palatomaxillary reconstruction by the senior author (m.l.u.) between 1998 and 2016. RESULTS: Twenty-one patients required multiple reconstructions. The median time to second reconstruction was 17 months. The most common reason for a second reconstruction was for recurrent disease (10 of 21), followed by functional/aesthetic reasons (7 of 21) and osteoradionecrosis (4 of 21). Four patients went on to have a third reconstruction, and two underwent a fourth. A total of 27 reconstructions were performed, consisting of 20 soft tissue free flaps, four vascularized bone free flaps, and three locoregional flaps. CONCLUSION: This patient cohort represents unique oncologic and reconstructive challenges. With long-term follow-up, multiple reconstructions may be required to optimize oncologic and functional/aesthetic outcomes. This is the first series of its kind that details the reasons for, as well as the outcomes of, patients who required multiple reconstructive procedures following initial palatomaxillary reconstruction. LEVEL OF EVIDENCE: 2B Laryngoscope, 130:2349-2353, 2020.

Ten patients with high-grade transformation of acinic cell carcinomas: Expression profiling of ß-catenin and cyclin D1 is useful.

Conventional acinic cell carcinoma (CACC) represents a prototypical low-grade salivary malignancy. Rarely, acinic cell carcinoma (ACC) can demonstrate aggressive features (zones of necrosis, apoptosis, varying nuclear atypia) warranting classification as "ACC with high-grade transformation" (HGT-ACC) or "dedifferentiated" ACC. This study reports ten new cases of HGT-ACC. There is potential for subtlety in recognizing high-grade transformation and distinguishing discrete nodules of necrosis from cytology aspiration changes. We compared immunohistochemical (IHC) profiles, specifically ß-catenin (bCAT) and cyclin D1 expression, which have been touted as potentially helpful in this context. We quantified morphology (primary axis nucleus, nuclear area and perimeter) in HGT-ACC and CACC. Clinical outcome is known for eight HGT-ACC patients; three patients developed locoregional or distant metastases, five remained disease-free. Nine of ten HGT-ACC expressed strong, diffuse, membranous bCAT. CACC demonstrated lower intensity of membranous bCAT expression. Strong, diffuse nuclear cyclin D1 was seen in five of ten HGT-ACC whereas no CACC demonstrated cyclin D1 with distribution greater than 50 %. The quantified nuclear morphologic features of CACC and HGT-ACC demonstrated overlapping means values. Maximum values for nuclear primary axis, area, and perimeter were greater for HGT-ACC versus CACC, corresponding to a subpopulation of larger tumor cells in HGT-ACC. The poor outcome associated with HGT-ACC justifies its recognition, which should alter surgical approach with respect to elective neck dissection or possible facial nerve sacrifice. With respect to ancillary IHC studies, strong, diffuse membranous bCAT expression, with or without strong nuclear cyclin D1 ≥ 50 % distribution or Ki67 index ≥ 25 % supports this diagnosis.

Effects of jaw exercise intervention timing on outcomes following oral and oropharyngeal cancer surgery: Pilot study.

BACKGROUND: Common in head and neck cancer patients, trismus can make speech and swallowing difficult and can compromise quality of life (QOL). Jaw range of motion exercise therapy may prevent or treat trismus in surgical patients. While the importance of these exercises is well-documented, there is little literature regarding the optimal timing of exercise initiation. METHODS: A prospective pilot study investigated the effects of early vs late jaw exercise intervention on postoperative jaw opening and QOL measures, which were examined descriptively. RESULTS: Timing of exercise intervention was not found to significantly impact the measured outcomes. However, provisional, descriptive findings showed that jaw opening was significantly associated with multiple QOL measures, with greater jaw opening associated with improved QOL. For certain QOL measures, this positive association was stronger at earlier time points than at later time points. CONCLUSIONS: The exploratory findings of this pilot study support further research into possible benefits of early jaw exercise intervention.