Computer-aided design and fabrication of nasal prostheses: a semi-automated algorithm using statistical shape modeling.

PURPOSE: This research aimed to develop an innovative method for designing and fabricating nasal prostheses that reduces anaplastologist expertise dependency while maintaining quality and appearance, allowing patients to regain their normal facial appearance. METHODS: The method involved statistical shape modeling using a morphable face model and 3D data acquired through optical scanning or CT. An automated design process generated patient-specific fits and appearances using regular prosthesis materials and 3D printing of molds. Manual input was required for specific case-related details. RESULTS: The developed method met all predefined requirements, replacing analog impression-making and offering compatibility with various data acquisition methods. Prostheses created through this method exhibited equivalent aesthetics to conventionally fabricated ones while reducing the skill dependency typically associated with prosthetic design and fabrication. CONCLUSIONS: This method provides a promising approach for both temporary and definitive nasal prostheses, with the potential for remote prosthesis fabrication in areas lacking anaplastology care. While new skills are required for data acquisition and algorithm control, these technologies are increasingly accessible. Further clinical studies will help validate its effectiveness, and ongoing technological advancements may lead to even more advanced and skill-independent prosthesis fabrication methods in the future.

Clinical validation of the accuracy of an intra-operative assessment tool using 3D ultrasound compared to histopathology in patients with squamous cell carcinoma of the tongue.

BACKGROUND: Histopathological analysis often shows close resection margins after surgical removal of tongue squamous cell carcinoma (TSCC). This study aimed to investigate the agreement between intraoperative 3D ultrasound (US) margin assessment and postoperative histopathology of resected TSCC. METHODS: In this study, ten patients were prospectively included. Three fiducial cannulas were inserted into the specimen. To acquire a motorized 3D US volume, the resected specimen was submerged in saline, after which images were acquired while the probe moved over the specimen. The US volumes were annotated twice: (1) automatically and (2) manually, with the automatic segmentation as initialization. After standardized histopathological processing, all hematoxylin-eosin whole slide images (WSI) were included for analysis. Corresponding US images were found based on the known WSI spacing and fiducials. Blinded observers measured the tumor thickness and the margin in the caudal, deep, and cranial directions on every slide. The anterior and posterior margin was measured per specimen. RESULTS: The mean difference in all measurements between manually segmented US and histopathology was 2.34 (SD: ±3.34) mm, and Spearman's rank correlation coefficient was 0.733 (p < 0.001). The smallest mean difference was in the tumor thickness with 0.80 (SD: ±2.44) mm and a correlation of 0.836 (p < 0.001). Limitations were observed in the caudal region, where no correlation was found. CONCLUSION: This study shows that 3D US and histopathology have a moderate to strong statistically significant correlation (r = 0.733; p < 0.001) and a mean difference between the modalities of 2.3 mm (95%CI: -4.2; 8.9). Future research should focus on patient outcomes regarding resection margins.

Implementing a deep learning model for automatic tongue tumour segmentation in ex-vivo 3-dimensional ultrasound volumes.

Three-dimensional (3D) ultrasound can assess the margins of resected tongue carcinoma during surgery. Manual segmentation (MS) is time-consuming, labour-intensive, and subject to operator variability. This study aims to investigate use of a 3D deep learning model for fast intraoperative segmentation of tongue carcinoma in 3D ultrasound volumes. Additionally, it investigates the clinical effect of automatic segmentation. A 3D No New U-Net (nnUNet) was trained on 113 manually annotated ultrasound volumes of resected tongue carcinoma. The model was implemented on a mobile workstation and clinically validated on 16 prospectively included tongue carcinoma patients. Different prediction settings were investigated. Automatic segmentations with multiple islands were adjusted by selecting the best-representing island. The final margin status (FMS) based on automatic, semi-automatic, and manual segmentation was computed and compared with the histopathological margin. The standard 3D nnUNet resulted in the best-performing automatic segmentation with a mean (SD) Dice volumetric score of 0.65 (0.30), Dice surface score of 0.73 (0.26), average surface distance of 0.44 (0.61) mm, Hausdorff distance of 6.65 (8.84) mm, and prediction time of 8 seconds. FMS based on automatic segmentation had a low correlation with histopathology (r = 0.12, p = 0.67); MS resulted in a moderate but insignificant correlation with histopathology (r = 0.4, p = 0.12, n = 16). Implementing the 3D nnUNet yielded fast, automatic segmentation of tongue carcinoma in 3D ultrasound volumes. Correlation between FMS and histopathology obtained from these segmentations was lower than the moderate correlation between MS and histopathology.

Comparison of image quality of 3D ultrasound: motorized acquisition versus freehand navigated acquisition, a phantom study.

PURPOSE: Intra-operative assessment of resection margins during oncological surgery is a field that needs improvement. Ultrasound (US) shows the potential to fulfill this need, but this imaging technique is highly operator-dependent. A 3D US image of the whole specimen may remedy the operator dependence. This study aims to compare and evaluate the image quality of 3D US between freehand acquisition (FA) and motorized acquisition (MA). METHODS: Multiple 3D US volumes of a commercial phantom were acquired in motorized and freehand fashion. FA images were collected with electromagnetic navigation. An integrated algorithm reconstructed the FA images. MA images were stacked into a 3D volume. The image quality is evaluated following the metrics: contrast resolution, axial and elevation resolution, axial and elevation distance calibration, stability, inter-operator variability, and intra-operator variability. A linear mixed model determined statistical differences between FA and MA for these metrics. RESULTS: The MA results in a statistically significant lower error of axial distance calibration (p < 0.0001) and higher stability (p < 0.0001) than FA. On the other hand, the FA has a better elevation resolution (p < 0.003) than the MA. CONCLUSION: MA results in better image quality of 3D US than the FA method based on axial distance calibration, stability, and variability. This study suggests acquiring 3D US volumes for intra-operative ex vivo margin assessment in a motorized fashion.

A hybrid registration method using the mandibular bone surface for electromagnetic navigation in mandibular surgery.

PURPOSE: To utilize navigated mandibular (reconstructive) surgery, accurate registration of the preoperative CT scan with the actual patient in the operating room (OR) is required. In this phantom study, the feasibility of a noninvasive hybrid registration method is assessed. This method consists of a point registration with anatomic landmarks for initialization and a surface registration using the bare mandibular bone surface for optimization. METHODS: Three mandible phantoms with reference notches on two osteotomy planes were 3D printed. An electromagnetic tracking system in combination with 3D Slicer software was used for navigation. Different configurations, i.e., different surface point areas and number and configuration of surface points, were tested with a dentate phantom (A) in a metal-free environment. To simulate the intraoperative environment and different anatomies, the registration procedure was also performed with an OR bed using the dentate phantom and two (partially) edentulous phantoms with atypical anatomy (B and C). The accuracy of the registration was calculated using the notches on the osteotomy planes and was expressed as the target registration error (TRE). TRE values of less than 2.0 mm were considered as clinically acceptable. RESULTS: In all experiments, the mean TRE was less than 2.0 mm. No differences were found using different surface point areas or number or configurations of surface points. Registration accuracy in the simulated intraoperative setting was-mean (SD)-0.96 (0.22), 0.93 (0.26), and 1.50 (0.28) mm for phantom A, phantom B, and phantom C. CONCLUSION: Hybrid registration is a noninvasive method that requires only a small area of the bare mandibular bone surface to obtain high accuracy in phantom setting. Future studies should test this method in clinical setting during actual surgery.

Registration methods for surgical navigation of the mandible: a systematic review.

Image-to-patient registration in navigated mandibular surgery is complex due to the mobile nature of the mandible compared with other craniofacial bones. As a result, surgical navigation is rarely employed in the mandibular region. This systematic review provides an overview of the different registration methods that are used for surgical navigation of the mandible. A systematic search was performed in the MEDLINE Ovid, Scopus, and Embase databases on March 25, 2021. Search terms included synonyms for mandibular surgery, surgical navigation, and registration methods. Articles about navigated mandibular surgery, where the registration method was explicitly mentioned, were included. The database search yielded a total of 2952 articles, from which 81 articles remained for analysis. Four main registration methods were identified: point registration, surface registration, hybrid registration, and computer vision-based registration. The mobility of the mandible is accounted for by either keeping the mandible in a fixed position during preoperative imaging and surgery, or by tracking the mandibular movements. Although different registration methods are available for navigated mandibular surgery, there is always a trade-off between accuracy, registration time, usability, and invasiveness. Future studies should focus on testing the different methods in larger patient studies and should report the registration accuracy.

Assessment of the deep resection margin during oral cancer surgery: A systematic review.

The main challenge for radical resection in oral cancer surgery is to obtain adequate resection margins. Especially the deep margin, which can only be estimated based on palpation during surgery, is often reported inadequate. To increase the percentage of radical resections, there is a need for a quick, easy, minimal invasive method, which assesses the deep resection margin without interrupting or prolonging surgery. This systematic review provides an overview of technologies that are currently being studied with the aim of fulfilling this demand. A literature search was conducted through the databases Medline, Embase and the Cochrane Library. A total of 62 studies were included. The results were categorized according to the type of technique: 'Frozen Section Analysis', 'Fluorescence', 'Optical Imaging', 'Conventional imaging techniques', and 'Cytological assessment'. This systematic review gives for each technique an overview of the reported performance (accuracy, sensitivity, specificity, positive predictive value, negative predictive value, or a different outcome measure), acquisition time, and sampling depth. At the moment, the most prevailing technique remains frozen section analysis. In the search for other assessment methods to evaluate the deep resection margin, some technologies are very promising for future use when effectiveness has been shown in larger trials, e.g., fluorescence (real-time, sampling depth up to 6 mm) or optical techniques such as hyperspectral imaging (real-time, sampling depth few mm) for microscopic margin assessment and ultrasound (less than 10 min, sampling depth several cm) for assessment on a macroscopic scale.

Electromagnetic surgical navigation in patients undergoing mandibular surgery.

The purpose of this study was to evaluate the feasibility of electromagnetic (EM) navigation for guidance on osteotomies in patients undergoing oncologic mandibular surgery. Preoperatively, a 3D rendered model of the mandible was constructed from diagnostic computed tomography (CT) images. Cutting guides and patient specific reconstruction plates were designed and printed for intraoperative use. Intraoperative patient registration was performed using a cone beam CT scan (CBCT). The location of the mandible was tracked with an EM sensor fixated to the mandible. The real-time location of both the mandible and a pointer were displayed on the navigation system. Accuracy measurements were performed by pinpointing four anatomical landmarks and four landmarks on the cutting guide using the pointer on the patient and comparing these locations to the corresponding locations on the CBCT. Differences between actual and virtual locations were expressed as target registration error (TRE). The procedure was performed in eleven patients. TREs were 3.2 ± 1.1 mm and 2.6 ± 1.5 mm using anatomical landmarks and landmarks on the cutting guide, respectively. The navigation procedure added on average half an hour to the duration of the surgery. This is the first study that reports on the accuracy of EM navigation in patients undergoing mandibular surgery.

Evaluating the accuracy of resection planes in mandibular surgery using a preoperative, intraoperative, and postoperative approach.

In mandibular surgery, three-dimensionally printed patient-specific cutting guides are used to translate the preoperative virtually planned resection planes to the operating room. This study was performed to determine whether cutting guides are positioned according to the virtual plan and to compare the intraoperative position of the cutting guide with the resection performed. Nine patients were included. The exact positions of the resection planes were planned virtually and a patient-specific cutting guide was designed and printed. After surgical placement of the cutting guide, intraoperative cone beam computed tomography (CBCT) was performed. Postoperative CT was used to obtain the final resection planes. Distances and yaw and pitch angles between the preoperative, intraoperative, and postoperative resection planes were calculated. Cutting guides were positioned on the mandible with millimetre accuracy. Anterior osteotomies were performed more accurately than posterior osteotomies (intraoperatively positioned and final resection planes differed by 1.2±1.0mm, 4.9±6.6°, and 1.8±1.5°, respectively, and by 2.2±0.9mm, 9.3±9°, and 8.3±6.5° respectively). Differences between intraoperatively planned and final resection planes imply a directional freedom of the saw through the saw slots. Since cutting guides are positioned with millimetre accuracy compared to the virtual plan, the design of the saw slots in the cutting guides needs improvement to allow more accurate resections.

Utilization of a 3D printed dental splint for registration during electromagnetically navigated mandibular surgery.

PURPOSE: A dental splint was developed for non-invasive rigid point-based registration in electromagnetically (EM) navigated mandibular surgery. Navigational accuracies of the dental splint were compared with the common approach, that is, using screws as landmarks. METHODS: A dental splint that includes reference registration notches was 3D printed. Different sets of three points were used for rigid point-based registration on a mandibular phantom: notches on the dental splint only, screws on the mandible, contralateral screws (the side of the mandible where the sensor is not fixated) and a combination of screws on the mandible and notches on the dental splint. The accuracy of each registration method was calculated using 45 notches at one side of the mandible and expressed as the target registration error (TRE). RESULTS: Average TREs of 0.83 mm (range 0.7-1.39 mm), 1.28 mm (1.03-1.7 mm), 2.62 mm (1.91-4.0 mm), and 1.34 mm (1.30-1.39 mm) were found, respectively, for point-based registration based on the splint only, screws on the mandible, screws on the contralateral side only, and screws combined with the splint. CONCLUSION: For dentate patients, rigid point-based registration performs best utilizing a dental splint with notches. The dental splint is easy to implement in the surgical, and navigational, workflow, and the notches can be pinpointed and designated on the CT scan with high accuracy. For edentate patients, screws can be used for rigid point-based registration. However, a new design of the screws is recommended to improve the accuracy of designation on the CT scan.

Intra-cavity Photodynamic Therapy for malignant tumors of the paranasal sinuses: An in vivo light dosimetry study.

BACKGROUND: Photodynamic therapy (PDT) is a promising treatment option for recurrent sinonasal malignancies. However, light administration in this area is challenging given the complex geometry, varying tissue optical properties and difficult accessibility. The goal of this study was to estimate the temporal and spatial variation in fluence and fluence rate during sinonasal mTHPC-mediated PDT. It was investigated whether the predetermined aim to illuminate with a fluence of 20 J⋅cm-2 and fluence rate of 100 mW⋅cm-2 was achieved. METHODS: In eleven patients the fluence and fluence rates were measured using in vivo light dosimetry at the target location during real-time sinonasal PDT. There was a variance in sinonasal target location and type of light diffuser used. In four patients two isotropic detectors were used within the same cavity. RESULTS: All measurements showed major fluence rate fluctuations within each single isotropic detector probe over time, as well as between probes within the same cavity. The largest fluence rate range measured was 328 mW⋅cm-2. Only one probe showed a mean fluence rate of ∼100 mW⋅cm-2. Taken all probes together, a fluence rate above 80 mW⋅cm-2 was measured in 31 % of the total light exposure; in 22 % it was less than 20 mW⋅cm-2. Thirty-three percent showed a fluence of at least 20 J⋅cm-2. CONCLUSIONS: The current dosimetry approach for sinonasal intra-cavity PDT shows major temporal and spatial variations in fluence rate and a large variance in light exposure time. The results emphasize the need for improvement of in vivo light dosimetry and dosimetry planning.

Ultrasound aids in intraoperative assessment of deep resection margins of squamous cell carcinoma of the tongue.

We wanted to find out whether ultrasound (US) can be used to assess the deep resection margins after excision of squamous cell carcinoma (SCC) of the tongue, as intraoperative feedback on their condition might help to prevent them being too close. Resected specimens of cancers of the tongue from 31 patients with SCC of the tongue were suspended in US gel and scanned with a small 5-10MHz US probe. The tumour was readily visible and US could differentiate it from muscle tissue. The margin of normal tongue musculature surrounding the tumour was measured on the US images, and the minimal resection margin was noted and compared with that reported by the histopathologist. The mean (SD) deep resection margins measured on the US images differed by 1.1 (0.9) mm from those reported by the histopathologist (Pearson's correlation coefficient: 0.79, p<0.01). The US measurements took a maximum of five minutes. It is feasible to use US to assess resection specimens of SCC of the tongue as an adjunct to existing strategies (such as frozen section analysis) to help achieve the desired deep surgical margins. The method is easy to incorporate into surgical routine as it does not take long.

The oral cavity tumor thickness: Measurement accuracy and consequences for tumor staging.

INTRODUCTION: In the 8th edition of the AJCC/UICC cancer staging system (AJCC8), the depth of invasion (DOI) of the oral cavity tumor is the discriminative factor in tumor staging over the previously used greatest dimension (GD). In order to obtain a complete representation of how accurate we stage oral cavity cancer clinically, we evaluated the accuracy of measurements of the tumor dimensions on ultrasound (US) and magnetic resonance (MR) imaging by comparing this with the histopathology as the "golden standard". Secondly, we compared the pathological tumor staging of these tumors according to the AJCC7 and AJCC8, to evaluate the effect of the incorporation of the DOI in the AJCC8. MATERIALS AND METHODS: In a retrospective analysis, including 85 oral cavity tumors, the GD and tumor thickness (TT) measured on US and MR, were compared to histopathology with a Pearson correlation coefficient (R) and a Bland-Altman plot. The tumors were staged according to both the AJCC7 and AJCC8. RESULTS: TT was more reliably measured with US (R = 0.67, limits of agreement = 10.7 mm), whereas GD was more reliably measured with MR (R = 0.69, limits of agreement = 25.7 mm). The AJCC8 staging resulted into a higher tumor stage in 21% of the cases, compared to the AJCC7. CONCLUSION: For preoperative tumor staging, the TT is best estimated by the use of US. The incorporation of DOI in the AJCC8 can result in a higher tumor stage in more than twenty percent of the patients, with an associated worse prognosis for the patient.

The best of both worlds: a hybrid approach for optimal pre- and intraoperative identification of sentinel lymph nodes.

PURPOSE: Hybrid image-guided surgery technologies such as combined radio- and fluorescence-guidance are increasingly gaining interest, but their added value still needs to be proven. In order to evaluate if and how fluorescence-guidance can help realize improvements beyond the current state-of-the-art in sentinel node (SN) biopsy procedures, use of the hybrid tracer indocyanine green (ICG)-99mTc-nancolloid was evaluated in a large cohort of patients. PATIENTS AND METHODS: A prospective trial was conducted (n = 501 procedures) in a heterogeneous cohort of 495 patients with different malignancies (skin malignancies, oral cavity cancer, penile cancer, prostate cancer and vulva cancer). After injection of ICG-99mTc-nanocolloid, SNs were preoperatively identified based on lymphoscintigraphy and SPECT/CT. Intraoperatively, SNs were pursued via gamma tracing, visual identification (blue dye) and/or near-infrared fluorescence imaging during either open surgical procedures (head and neck, penile, vulvar cancer and melanoma) or robot assisted laparoscopic surgery (prostate cancer). As the patients acted as their own control, use of hybrid guidance could be compared to conventional radioguidance and the use of blue dye (n = 300). This was based on reported surgical complications, overall survival, LN recurrence free survival, and false negative rates (FNR). RESULTS: A total of 1,327 SN-related hotspots were identified on 501 preoperative SPECT/CT scans. Intraoperatively, a total number of 1,643 SNs were identified based on the combination of gamma-tracing (>98%) and fluorescence-guidance (>95%). In patients wherein blue dye was used (n = 300) fluorescence-based SN detection was superior over visual blue dye-based detection (22-78%). No adverse effects related to the use of the hybrid tracer or the fluorescence-guidance procedure were found and outcome values were not negatively influenced. CONCLUSION: With ICG-99mTc-nanocolloid, the SN biopsy procedure has become more accurate and independent of the use of blue dye. With that, the procedure has evolved to be universal for different malignancies and anatomical locations.

[The role of photodynamic therapy for the treatment of stage I and II carcinoma of the lip]. / De rol van fotodynamische therapie bij de behandeling van het stadium I en II lipcarcinoom.

In this research project the outcomes of photodynamic therapy for the treatment of stage I and II carcinoma of the lip are presented. Retrospectively, 15 patients diagnosed with a primary stage I or II lip carcinoma and treated with meta-tetra hydroxyphenyl chlorin mediated photodynamic therapy were evaluated. The primary outcome measure was disease free survival; the secondary outcome measure was the functional and aesthetic outcome after treatment. A total of 16 primary lip carcinomas were evaluated (75% stage I; 25% stage II). In 94% of the primary lip carcinomas, photodynamic therapy led to a complete remission after a variable follow-up of 14 months to 11 years. The functional and aesthetic long-term outcomes were considered excellent. Photodynamic therapy for the treatment of stage I and II lip carcinoma has a disease free survival rate comparable to surgery or radiotherapy and has outstanding functional and aesthetic outcomes.

Remarkable response to photodynamic therapy in residual T4N0M0 nasopharyngeal carcinoma: a case report.

Local treatment of residual or recurrent nasopharyngeal carcinoma (NPC) is a challenge. Photodynamic therapy (PDT) is an established treatment modality for incurable head and neck carcinoma. Several studies reported induction of an immune response after PDT. We present a patient with residual T4N0M0 NPC who was treated with PDT for residual disease after initial treatment with neo-adjuvant chemotherapy and radiotherapy. Five years after PDT, the tumor did not progress and the patient is still in good condition. We discuss this remarkable long-term response to PDT and speculate on possible mechanisms.