Automated 3-D Computer-Aided Measurement of the Bony Orbit: Evaluation of Correlations among Volume, Depth, and Surface Area.

(1)The study aimed to measure the depth, volume, and surface area of the intact human orbit by applying an automated method of CT segmentation and to evaluate correlations among depth, volume, and surface area. Additionally, the relative increases in volume and surface area in proportion to the diagonal of the orbit were assessed. (2) CT data from 174 patients were analyzed. A ball-shaped mesh consisting of tetrahedral elements was inserted inside orbits until it encountered the bony boundaries. Orbital volume, area depth, and their correlations were measured. For the validation, an ICC was used. (3) The differences between genders were significant (p < 10-7) but there were no differences between sides. When comparing orbit from larger to smaller, a paired sample t-test indicated a significant difference in groups (p < 10-10). A simple linear model (Volume~1 + Gender + Depth + Gender:Depth) revealed that only depth had a significant effect on volume (p < 10-19). The ICCs were 1.0. (4) Orbital volume, depth, and surface area measurements based on an automated CT segmentation algorithm demonstrated high repeatability and reliability. Male orbits were always larger on average by 14%. There were no differences between the sides. The volume and surface area ratio did not differ between genders and was approximately 0.75.

Survival of dental implants and occurrence of mucosal overgrowth in patients with head and neck cancer treated with/without radiotherapy and mucosal graft-two-year follow-up.

OBJECTIVES: The primary aim of the present study was to compare head and neck cancer treatment modality surgery and surgery with radiotherapy or chemoradiotherapy alone for dental implant (DI) survival. The second aim was to evaluate the prevalence of mucosal overgrowth around DI after treatment with or without mucosal grafts. MATERIALS AND METHODS: An observational retrospective study consisted of 59 patients with malignant head and neck tumors that received DI between 2015 and 2019. Treatment modalities together with information on oral rehabilitation with DI, prevalence of mucosal overgrowth, and precursor lesions were gathered from the hospital records. Radiation doses were determined using a sum of three-dimensional dose distributions. RESULTS: Overall DI survival rate was 88%, in irritated jaw 89%, and in nonirradiated jaw 88% in this observational period (p = 0.415, mean follow-up was 2 years 10 months, range 9-82 months). Mucosal overgrowth was found in 42 of 196 implants (21%), of which 36 cases (86%) were associated in grafted areas (p < 0.001). Oral lichen planus/lichenoid reaction was diagnosed in 14 of all 59 (24%) oral cancer patients. CONCLUSION: Implant survival was not significantly influenced by radiation therapy in this observational period. In grafted bone, implant survival was significantly inferior than in native bone. Mucosal overgrowth around implants was more common in mucosal grafted areas versus nongrafted. CLINICAL RELEVANCE: This study demonstrates the impact of grafted bone to dental implant survival rate and mucosal overgrowth.

The effect of matrices on the gene expression profile of patient-derived head and neck carcinoma cells for in vitro therapy testing.

OBJECTIVE: Head and neck squamous cell carcinoma (HNSCC) is a highly aggressive tumor with a 5-year mortality rate of ~ 50%. New in vitro methods are needed for testing patients' cancer cell response to anti-cancer treatments. We aimed to investigate how the gene expression of fresh carcinoma tissue samples and freshly digested single cancer cells change after short-term cell culturing on plastic, Matrigel or Myogel. Additionally, we studied the effect of these changes on the cancer cells' response to anti-cancer treatments. MATERIALS/METHODS: Fresh tissue samples from HNSCC patients were obtained perioperatively and single cells were enzymatically isolated and cultured on either plastic, Matrigel or Myogel. We treated the cultured cells with cisplatin, cetuximab, and irradiation; and performed cell viability measurement. RNA was isolated from fresh tissue samples, freshly isolated single cells and cultured cells, and RNA sequencing transcriptome profiling and gene set enrichment analysis were performed. RESULTS: Cancer cells obtained from fresh tissue samples changed their gene expression regardless of the culturing conditions, which may be due to the enzymatic digestion of the tissue. Myogel was more effective than Matrigel at supporting the upregulation of pathways related to cancer cell proliferation and invasion. The impacts of anti-cancer treatments varied between culturing conditions. CONCLUSIONS: Our study showed the challenge of in vitro cancer drug testing using enzymatic cell digestion. The upregulation of many targeted pathways in the cultured cells may partially explain the common clinical failure of the targeted cancer drugs that pass the in vitro testing.

Carotid interposition in patients with head and neck tumors: clinical experience of 13 cases reconstructed with a great saphenous vein autograft.

BACKGROUND: Carotid interposition graft (CIG) surgery in the setting of head & neck cancer (HNC) is a rare procedure with a limited number of cases described in the literature. AIMS/OBJECTIVES: To assess the outcomes of the surgery at Helsinki University Hospital. MATERIALS AND METHODS: Patients who underwent CIG in a head and neck tumor surgery were retrospectively analyzed over 15 years. Overall-survival (OS) was calculated until 1 May 2020. The primary-outcome was to measure the 30-day OS, postoperative stroke rate, and other complications. The secondary-outcome was to measure 1-, 2-, and 5-year OS. RESULTS: Thirteen patients were identified, 11 with HNC and two with Shamblin III Carotid Body Tumors. The great saphenous vein was used for all vascular reconstructions, and shunting was routinely performed. The 30-day stroke incidence was nil. Two graft-blowouts were encountered, one of which lead to death and the other was successfully managed. For HNC patients, the locoregional recurrence-rate was 36%. The 5-year OS was 46.2%. CONCLUSION AND SIGNIFICANCE: CIG in HNC setting can achieve oncologic-control with an acceptable rate of complications. Routine shunting, heparinization, and elevating blood-pressure during closure seem to be safe protocols to maintain cerebral-circulation perioperatively. A moderate graft-blowout risk should be considered.

Patient-Specific Bioimplants and Reconstruction Plates for Mandibular Defects: Production Workflow and In Vivo Large Animal Model Study.

A major challenge with extensive craniomaxillofacial bone reconstruction is the limited donor-site availability to reconstruct defects predictably and accurately according to the anatomical shape of the patient. Here, patient-specific composite bioimplants, consisting of cross-linked poly(trimethylene carbonate) (PTMC) networks and ß-tricalcium phosphate (ß-TCP), are tested in vivo in twelve Göttingen minipigs in a large mandibular continuity defect model. The 25 mm defects are supported by patient-specific titanium reconstruction plates and receive either osteoconductive composite bioimplants (PTMC+TCP), neat polymer network bioimplants (PTMC), autologous bone segments (positive control), or are left empty (negative control). Postoperatively, defects treated with bioimplants show evident ossification at 24 weeks. Histopathologic evaluation reveals that neat PTMC bioimplant surfaces are largely covered with fibrous tissue, while in the PTMC+TCP bioimplants, bone attached directly to the implant surface shows good osteoconduction and histological signs of osteoinductivity. However, PTMC+TCP bioimplants are associated with high incidence of necrosis and infection, possibly due to rapid resorption and/or particle size of the used ß-TCP. The study highlights the importance of testing bone regeneration implants in a clinically relevant large animal model and at the in situ reconstruction site, since results on small animal models and studies in nonloadbearing areas do not translate directly.

The combined anterolateral thigh-Partial iliac crest minihybrid free flap for mandibular reconstruction.

BACKGROUND AND AIMS: Tumors of the oral cavity often require extensive resections leading to significant hard and soft tissue defects. Microvascular free flaps, consisting of both hard and soft tissue, are often required in reconstructions. Hybrid flaps, composed of two different joint free flaps, offer potential alternatives for head and neck reconstruction. This report presents our results with a modified hybrid ALT/DCIA, that is, minihybrid free flap (MH-flap) composed of the anterolateral thigh (ALT) and a partial inner lamina iliac crest only (partial DCIA) for reconstruction of the mandibular region. PATIENTS AND METHODS: Eight patients underwent oral cancer reconstruction of the mandible with the MH-flap. The MH-flap was harvested sparing the outer crest and lamina of crista, and its pedicle was combined to the distal pedicle of ALT. Clinical data and postoperative complications were analyzed. RESULTS: The mean length of the osseous graft was 64 mm (range 54-78 mm). None of the patients had complications requiring surgical intervention. No donor site complications were observed. The overall survival rate was 100%. The mean length of follow-up was 16 months (range 7-30 months). CONCLUSIONS: According to our results, the ALT-partial DCIA MH-flap has postoperative outcomes comparable to those of the fibular flap. The flap is a good option with excellent bone properties for reconstruction of limited mandibular defects not suitable for fibular or scapular reconstruction.

Virtual 3D planning and prediction accuracy in two bimaxillary face transplantations in Helsinki.

BACKGROUND: The aim of this study was to describe the 3D planning process used in our two composite face transplantations and to analyze the accuracy of a virtual transplantation in predicting the end-result of face transplantation. METHODS: The study material consists of two bimaxillary composite face transplantations performed in the Helsinki University Hospital in 2016 and 2018. Computed tomography (CT) scans of the recipient and donor were used to define the osteotomy lines and perform the virtual face transplantation and to 3D print customized osteotomy guides for recipient and donor. Differences between cephalometric linear and angular measurements of the virtually simulated and the actual postoperative face transplantation were calculated. RESULTS: No changes to the planned osteotomy lines were needed during surgery. The differences in skeletal linear and angular measurements of the virtually simulated predictions and the actual postoperative face transplantations of the two patients varied between 0.1-5.6 mm and 0.7°-4°. The postoperative skeletal relationship between maxilla and mandible in both patients were almost identical in comparison to the predictions. CONCLUSIONS: 3D planning is feasible and provides close to accurate bone reconstruction in face transplantation. Preoperative virtual transplantation assists planning and improves the outcome in bimaxillary face transplantation.

Oral findings and treatment of patients with face transplants in Helsinki.

OBJECTIVES: Oral health and balanced occlusion are important aspects of a well-functioning face transplant. This study describes the oral and dental status, dental management, and sialoendoscopy of the first 2 patients in Helsinki who underwent face transplantations. STUDY DESIGN: Two patients received near-full face transplantations in 2016 and 2018, respectively. The transplanted tissues included a Le Fort type II maxilla, angle-to-angle mandible, all oral mucosa, ventral tongue tissue, and the muscles of the floor of the mouth. Comprehensive oral examinations and all required dental treatment, including follow-up examinations, were performed for both patients after the transplantations. RESULTS: Both patients rehabilitated well, and their quality of life improved. Stable, functioning dentition and occlusion were achieved for both patients. Hyposalivation and dental caries were issues for both patients. Patient 1 also experienced infections in the jaws. Implants were placed in the transplanted jaws of patient 2 with successful osseointegration. CONCLUSIONS: We report successful tooth-bearing face transplantations in 2 patients. Patient selection, particularly regarding oral health, is crucial in avoiding posttransplantation complications. Moreover, the oral and dental status of the donor should be examined by a dentist before transplantation, and regular follow-up dental examinations should be performed after transplantation.

In vitro humanized 3D microfluidic chip for testing personalized immunotherapeutics for head and neck cancer patients.

OBJECTIVES: Immunotherapy and personalized medicine therapeutics are emerging as promising approaches in the management of head and neck squamous cell carcinoma (HNSCC). In spite of that, there is yet no assay that could predict individual response to immunotherapy. METHODS: We manufactured an in vitro 3D microfluidic chip to test the efficacy of immunotherapy. The assay was first tested using a tongue cancer cell line (HSC-3) embedded in a human tumour-derived matrix "Myogel/fibrin" and immune cells from three healthy donors. Next, the chips were used with freshly isolated cancer cells, patients' serum and immune cells. Chips were loaded with different immune checkpoint inhibitors, PD-L1 antibody and IDO 1 inhibitor. Migration of immune cells towards cancer cells and the cancer cell proliferation rate were evaluated. RESULTS: Immune cell migration towards HSC-3 cells was cancer cell density dependent. IDO 1 inhibitor induced immune cells to migrate towards cancer cells both in HSC-3 and in two HNSCC patient samples. Efficacy of PD-L1 antibody and IDO 1 inhibitor was patient dependent. CONCLUSION: We introduced the first humanized in vitro microfluidic chip assay to test immunotherapeutic drugs against HNSCC patient samples. This assay could be used to predict the efficacy of immunotherapeutic drugs for individual patients.

PCR-based zebrafish model for personalised medicine in head and neck cancer.

BACKGROUND: Currently, in vivo model for personalised cancer drug testing is challenging. A zebrafish larvae xenograft model has been applied in recent years to cancer research, particularly for drug testing purposes, showing promising results in drug testing against patient-derived tumour xenografts. Currently, these xenograft models apply imaging techniques to measure drug efficacy. However, this method carries several limitations, including timely imaging, thereby reducing the available number of tested fish and drugs. Here, we propose a PCR-based fast assay to evaluate drug efficacy in a zebrafish larvae xenograft model. METHODS: We tested two primary and corresponding metastatic head and neck squamous cell carcinoma (HNSCC) cell lines and patient-derived tongue cancer sample applying zebrafish larvae xenograft model. Cisplatin efficacy was tested using imaging technique and compared the results with PCR-based methods. Drug screening of eight compounds was applied on both cell lines and patient sample using PCR. RESULTS: In a head-to-head comparison, all the three techniques (imaging, quantitative PCR, and droplet digital PCR) showed similar reduction of the cancer cells growth after cisplatin treatment. Using the quantitative PCR assay, we demonstrated a dose-dependent response of HNSCC cells to cisplatin. Drug screening results of four HNSCC cell lines and patient sample revealed different drug efficacy between tested cancer cells. CONCLUSION: We introduce a novel, easy, fast and cost-effective PCR-based in vivo zebrafish larvae assay to test the response of cell lines and clinical tumour samples to anti-cancer drugs. This method goes hand-by-hand with the commonly used imaging assay.

The Helsinki Face Transplantation: Surgical aspects and 1-year outcome.

BACKGROUND: Since 2005, at least 38 facial transplantations have been performed worldwide. We herein describe the surgical technique and 1-year clinical outcome in Finland's first face transplant case. METHODS: A 34-year-old male who had a severe facial deformity following ballistic trauma in 1999 underwent facial transplantation at the Helsinki University Hospital on 8th February 2016. Three-dimensional (3D) technology was used to manufacture donor and recipient patient-specific osteotomy guides and a donor face mask. The facial transplant consisted of a Le Fort II maxilla, central mandible, lower ⅔ of the midface muscles, facial and neck skin, oral mucosa, anterior tongue and floor of mouth muscles, facial nerve (three bilateral branches), and bilateral hypoglossal and buccal nerves. RESULTS: At 1-year follow-up, there have thus far been no clinical or histological signs of rejection. The patient has a good aesthetic outcome with symmetrical restoration of the mobile central part of the face, with recovery of pain and light touch sensation to almost the entire facial skin and intraoral mucosa. Electromyography at 1 year has confirmed symmetrical muscle activity in the floor of the mouth and facial musculature, and the patient is able to produce spontaneous smile. Successful social and psychological outcome has also been observed. Postoperative complications requiring intervention included early (nasopalatinal fistula, submandibular sialocele, temporomandibular joint pain and transient type 2 diabetes) and late (intraoral wound and fungal infection, renal impairment and hypertension) complications. CONCLUSION: At 1 year, we report an overall good functional outcome in Finland's first face transplant.

Rapid prototyped patient specific guiding implants in critical mandibular reconstruction.

Large tumours of the mandible need immediate reconstruction to provide continuity of the mandible, satisfactory function of the jaw, as well as an acceptable aesthetic outcome. In this prospective study we described the immediate reconstruction of the mandible using computer aided design and 15 rapid prototyped patient specific implants (PSI) in 14 patients suffering from benign or malignant tumours demanding continuity resection of the mandible. The scaffold PSI was filled with ß-tricalcium phosphate granules and autologous bone. Microvascular reconstruction was additionally needed in 12/15 cases. The clinical follow up was on average 33 months and the radiological follow up was on average 21 months. In nine cases the healing was uneventful. One patient lost the microvascular flap during the first postoperative week and one patient needed a revision due to perforation of the mucosa at the site of the PSI. Four patients had a major complication due to perforation of the mucosa leading to infection, which resulted in the total or partial removal of the PSI. The PSI seems to be a promising solution for treatment of patients demanding large reconstruction after mandible resection. The benefits are decreased rate of donor site complications and more accurate and prompt surgical procedure.

Rapid prototyping modelling in oral and maxillofacial surgery: A two year retrospective study.

BACKGROUND: The use of rapid prototyping (RP) models in medicine to construct bony models is increasing. MATERIAL AND METHODS: The aim of the study was to evaluate retrospectively the indication for the use of RP models in oral and maxillofacial surgery at Helsinki University Central Hospital during 2009-2010. Also, the used computed tomography (CT) examination - multislice CT (MSCT) or cone beam CT (CBCT) - method was evaluated. RESULTS: In total 114 RP models were fabricated for 102 patients. The mean age of the patients at the time of the production of the model was 50.4 years. The indications for the modelling included malignant lesions (29%), secondary reconstruction (25%), prosthodontic treatment (22%), orthognathic surgery or asymmetry (13%), benign lesions (8%), and TMJ disorders (4%). MSCT examination was used in 92 and CBCT examination in 22 cases. Most of the models (75%) were conventional hard tissue models. Models with colored tumour or other structure(s) of interest were ordered in 24%. Two out of the 114 models were soft tissue models. CONCLUSIONS: The main benefit of the models was in treatment planning and in connection with the production of pre-bent plates or custom made implants. The RP models both facilitate and improve treatment planning and intraoperative efficiency. KEY WORDS: Rapid prototyping, radiology, computed tomography, cone beam computed tomography.

The use of anatomically drop-shaped bioactive glass S53P4 implants in the reconstruction of orbital floor fractures--A prospective long-term follow-up study.

An isolated fracture of the orbital floor needs reconstruction if there is a clear herniation of adipose tissue or of the rectus inferior muscle into the maxillary sinus. A prospective study was carried out treating 20 patients with an isolated blow-out fracture of the orbital floor or with a combined zygomatico-orbito-maxillary complex fracture, using a newly designed anatomically drop-shaped implants made of bioactive glass (BAG) S53P4. Computed tomography (CT) was performed immediately postoperatively to confirm the correct position of the plate. The patients were followed up for an average of 32 months clinically and radiologically with magnetic resonance imaging (MRI) for an average of 31 months. None of the patients had any signs of complications related to the implant and the clinical outcome was very good. None of the patients had persisting diplopia. The level of the pupillas was normal in 15 of 20 patients. Minor hypo-ophthalmos ranging from 0.5 to 1.0 mm was observed in three patients, and moderate hypo-ophthalmos of 2.0 mm was seen in one patient. Hyperophthalmos of 1.0 mm was seen in one patient. Minor enophthalmos on the operated side ranging from 0.5 to 1.0 mm was seen in eight patients. Mild to moderate paraesthesia of the infraorbital nerve was observed in six patients. The immediate postoperative CT and the long term follow-up MRI revealed that the drop-shaped BAG implants retained their correct position in the orbital floor and did not show any evidence of losing their original shape or material resorption. No adverse tissue reaction was associated with the material. Due to the anatomical drop shape, the implants could successfully maintain the orbital volume and compensate for the retrobulbar adipose tissue atrophy.

Rapidly growing and ulcerating metastatic renal cell carcinoma of the lower lip: A case report and review of the literature.

Renal cell carcinomas (RCCs) have a tendency to metastasize at an early stage, therefore, the patients frequently exhibit metastatic disease at the time of diagnosis. Common locations for the metastases are adjacent organs and abdominal lymph nodes; however, occasionally metastasis to the peripheral organs may be the initial clinical symptom. The 71-year-old male patient in the current case suffered from radioresistant and aggressively behaving RCC metastasis in the mandible and lower lip, which was successfully managed by surgical resection. RCC metastasis to the facial area is considered to be uncommon based on a review of the existing literature. RCC are somewhat radioresistant and therefore, palliative surgery must be considered when treating patients with this metastatic disease.

Rapid prototyped patient specific implants for reconstruction of orbital wall defects.

Defects of orbital walls can be reconstructed using implants. The authors report a safe and accurate method to reconstruct bone defects in the orbital area using patient specific implants. A detailed process description of computer aided design (CAD) reconstructive surgery (CRS) is introduced in this prospective study. The 3D volumetric virtual implant was design using MSCT data and PTCProEngineer™ 3D software. The intact orbital cavity of twelve patients was mirrored to the injured side. Specific ledges steered the implant into correct place. Postoperatively the position was assessed using image fusion. One implant (8%) was rejected due to chemical impurities, two (16%) had a false shape due to incorrect CAD. Data of thin bone did not transfer correctly to CAD and resulted in error. One implant (8%) was placed incorrectly. Duration of the CRS was in average 1.17 h, correspondingly 1.57 h using intraoperative bending technique. The CRS process has several critical stages, which are related to converting data and to incompatibility between software. The CRS process has several steps that need further studies. The data of thin bone may be lost and disturb an otherwise very precise technique. The risk of incorporating impurities into the implant must be carefully controlled.

Impairment of wound healing after operative treatment of mandibular fractures, and the influence of dexamethasone.

Our aim was to clarify the incidence of impaired wound healing after open reduction and ostheosynthesis of mandibular fractures, and to find out whether the use of dexamethasone during the operation increased the risk. Patients were drawn from a larger group of healthy adult dentate patients who had participated in a single-blind, randomised study, the aim of which was to clarify the benefits of operative dexamethasone after treatment of facial fractures. The present analysis comprised 41 patients who had had open reduction and fixation of mandibular fractures with titanium miniplates and monocortical screws through one or 2 intraoral approaches. The outcome variable was impaired healing of the wound. The primary predictive variable was the perioperative use of dexamethasone; other potential predictive variables were age, sex, smoking habit, type of fracture, delay in treatment, and duration of operation. Wound healing was impaired in 13/41 patients (32%) (13/53 of all fractures). The incidence among patients who were given dexamethasone and those who were not did not differ significantly. Only age over 25 was significantly associated with delayed healing (p=0.02). The use of dexamethasone 30 mg perioperatively did not significantly increase the risk of impaired wound healing in healthy patients with clinically uninfected mandibular fractures fixed with titanium miniplates through an intraoral approach. Older age is a significant predictor of impaired healing, which emphasises the importance of thorough anti-infective care in these patients during and after the operation.

A rare case of oral epithelioid sarcoma of the gingiva.

Epithelioid sarcoma (ES) is a rare malignant soft tissue tumor. ES can be classified into proximal, distal, and fibroma-like subtypes. These tumors show both mesenchymal and epithelial immunophenotypes. Microscopically, the proximal type ES is usually characterized by nodules of spindle and epithelioid cells growing in granuloma-like pattern often presenting with central necrosis. Immunohistochemically these tumors are vimentin, pancytokeratin, and usually EMA (80%) positive. CD34 (50%) and CD99 (25%) may be positive, and occasionally SMA and S-100 immunopositivity has been reported. No specific genetic alterations have been found in ES. As far as we know, this is the first case in the literature to present ES in gingival mucosa.

A rare case of spinal cord metastases from oral SCC.

Oral squamous cell carcinoma (SCC) tends to spread by direct extension, lymphatic metastases and has low incidence of haematogenous spread. Intramedullary and intradural spinal cord metastases are rare in general. We present a patient case with an aggressive oral SCC which developed intradural and intramedullary multiple spinal cord metastases.