Over the past decade, the demand for three-dimensional (3D) patient-specific (PS) modelling and s... more Over the past decade, the demand for three-dimensional (3D) patient-specific (PS) modelling and simulations has increased considerably; they are now widely available and generally accepted as part of patient care. However, the patient specificity of current PS designs is often limited to this patient-matched fit and lacks individual mechanical aspects, or parameters, that conform to the specific patient’s needs in terms of biomechanical acceptance. Most biomechanical models of the mandible, e.g., finite element analyses (FEA), often used to design reconstructive implants or total joint replacement devices for the temporomandibular joint (TMJ), make use of a literature-based (mean) simplified muscular model of the masticatory muscles. A muscle’s cross-section seems proportionally related to its maximum contractile force and can be multiplied by an intrinsic strength constant, which previously has been calculated to be a constant of 37 [N/cm2]. Here, we propose a contemporary method t...
Due to the introduction of three-dimensional (3D) technology in surgery, it has become possible t... more Due to the introduction of three-dimensional (3D) technology in surgery, it has become possible to preoperatively plan complex bone resections and reconstructions, (corrections and adjustments related to bones), from head to toe [...]
We present an articulatory synthesis framework for the synthesis and manipulation of oral cancer ... more We present an articulatory synthesis framework for the synthesis and manipulation of oral cancer speech for clinical decision making and alleviation of patient stress. Objective and subjective evaluations demonstrate that the framework has acceptable naturalness and is worth further investigation. A subsequent subjective vowel and consonant identification experiment showed that the articulatory synthesis system can manipulate the articulatory trajectories so that the synthesised speech reproduces problems present in the ground truth oral cancer speech.
Accurate mandible segmentation is significant in the field of maxillofacial surgery to guide clin... more Accurate mandible segmentation is significant in the field of maxillofacial surgery to guide clinical diagnosis and treatment and develop appropriate surgical plans. In particular, cone-beam computed tomography (CBCT) images with metal parts, such as those used in oral and maxillofacial surgery (OMFS), often have susceptibilities when metal artifacts are present such as weak and blurred boundaries caused by a high-attenuation material and a low radiation dose in image acquisition. To overcome this problem, this paper proposes a novel deep learning-based approach (SASeg) for automated mandible segmentation that perceives overall mandible anatomical knowledge. SASeg utilizes a prior shape feature extractor (PSFE) module based on a mean mandible shape, and recurrent connections maintain the continuity structure of the mandible. The effectiveness of the proposed network is substantiated on a dental CBCT dataset from orthodontic treatment containing 59 patients. The experiments show that...
Accurate segmentation of the mandible from cone-beam computed tomography (CBCT) scans is an impor... more Accurate segmentation of the mandible from cone-beam computed tomography (CBCT) scans is an important step for building a personalized 3D digital mandible model for maxillofacial surgery and orthodontic treatment planning because of the low radiation dose and short scanning duration. CBCT images, however, exhibit lower contrast and higher levels of noise and artifacts due to extremely low radiation in comparison with the conventional computed tomography (CT), which makes automatic mandible segmentation from CBCT data challenging. In this work, we propose a novel coarse-to-fine segmentation framework based on 3D convolutional neural network and recurrent SegUnet for mandible segmentation in CBCT scans. Specifically, the mandible segmentation is decomposed into two stages: localization of the mandible-like region by rough segmentation and further accurate segmentation of the mandible details. The method was evaluated using a dental CBCT dataset. In addition, we evaluated the proposed ...
Three-dimensional technology is increasingly being used in acetabular fracture treatment. No syst... more Three-dimensional technology is increasingly being used in acetabular fracture treatment. No systematic reviews are available about the added clinical value of 3D-assisted acetabular fracture surgery compared to conventional surgery. Therefore, this study aimed to investigate whether 3D-assisted acetabular fracture surgery compared to conventional surgery improves surgical outcomes in terms of operation time, intraoperative blood loss, intraoperative fluoroscopy usage, complications, and postoperative fracture reduction, and whether it improves physical functioning. Pubmed and Embase databases were searched for articles on 3D technologies in acetabular fracture surgery, published between 2010 and February 2021. The McMaster critical review form was used to assess the methodological quality. Differences between 3D-assisted and conventional surgery were evaluated using the weighted mean and odds ratios. Nineteen studies were included. Three-dimensional-assisted surgery resulted in sig...
Due to the complex anatomical shape of the pelvis, screw placement can be challenging in acetabul... more Due to the complex anatomical shape of the pelvis, screw placement can be challenging in acetabular fracture surgery. This study aims to assess the accuracy of screw placement using patient-specific surgical drilling guides applied to pre-contoured conventional implants in acetabular fracture surgery. CT scans were made of four human cadavers to create 3D models of each (unfractured) pelvis. Implants were pre-contoured on 3D printed pelvic models and optically scanned. Following virtual preoperative planning, surgical drilling guides were designed to fit on top of the implant and were 3D printed. The differences between the pre-planned and actual screw directions (degrees) and screw entry points (mm) were assessed from the pre- and postoperative CT-scans. The median difference between the planned and actual screw direction was 5.9° (IQR: 4–8°) for the in-plate screws and 7.6° (IQR: 6–10°) for the infra-acetabular and column screws. The median entry point differences were 3.6 (IQR: 2...
6016Background: Salivary Duct Carcinoma (SDC) is a rare, highly aggressive subtype of salivary gl... more 6016Background: Salivary Duct Carcinoma (SDC) is a rare, highly aggressive subtype of salivary gland cancer, which is androgen receptor (AR) positive in most pts. In recurrent disease androgen deprivation therapy (ADT) can be used, however only limited data are available. The aim of this study was to evaluate clinical outcome, to identify prognostic factors for overall survival (OS) and to retrospectively analyze efficacy of ADT. Methods: The nationwide network and registry of histo- and cytopathology (PALGA) identified all adult pts with SDC between 1990 - 2014 in the Netherlands. Lymph node ratio (LNR) was defined as the number of positive LN divided by the total number of LN after neck dissection. Survival analyses were conducted using Kaplan-Meier method. The Cox proportional hazard model was used to identify prognostic factors on uni- and multivariable analyses. Results: A total of 157 pts with SDC were identified. Median age was 66 years, 77% were male. AR and HER2neu were positive in 100% and 44%, ...
Journal of the National Comprehensive Cancer Network, 2018
Background: Monitoring and effectively improving oncologic integrated care requires dashboard inf... more Background: Monitoring and effectively improving oncologic integrated care requires dashboard information based on quality registrations. The dashboard includes evidence-based quality indicators (QIs) that measure quality of care. This study aimed to assess the quality of current integrated head and neck cancer care with QIs, the variation between Dutch hospitals, and the influence of patient and hospital characteristics. Methods: Previously, 39 QIs were developed with input from medical specialists, allied health professionals, and patients' perspectives. QI scores were calculated with data from 1,667 curatively treated patients in 8 hospitals. QIs with a sample size of >400 patients were included to calculate reliable QI scores. We used multilevel analysis to explain the variation. Results: Current care varied from 29% for the QI about a case manager being present to discuss the treatment plan to 100% for the QI about the availability of a treatment plan. Variation between hospitals was small for the QI about patients discussed in multidisciplinary team meetings (adherence: 95%, range 88%-98%), but large for the QI about malnutrition screening (adherence: 50%, range 2%-100%). Higher QI scores were associated with lower performance status, advanced tumor stage, and tumor in the oral cavity or oropharynx at the patient level, and with more curatively treated patients (volume) at hospital level. Conclusions: Although the quality registration was only recently launched, it already visualizes hospital variation in current care. Four determinants were found to be influential: tumor stage, performance status, tumor site, and volume. More data are needed to assure stable results for use in quality improvement.
Current Opinion in Otolaryngology & Head & Neck Surgery, 2018
Purpose of review This review describes the advances in 3D virtual planning for mandibular and ma... more Purpose of review This review describes the advances in 3D virtual planning for mandibular and maxillary reconstruction surgical defects with full prosthetic rehabilitation. The primary purpose is to provide an overview of various techniques that apply 3D technology safely in primary and secondary reconstructive cases of patients suffering from head and neck cancer. Recent findings Methods have been developed to overcome the problem of control over the margin during surgery while the crucial decision with regard to resection margin and planning of osteotomies were predetermined by virtual planning. The unlimited possibilities of designing patient-specific implants can result in creative uniquely applied solutions for single cases but should be applied wisely with knowledge of biomechanical engineering principles.
Background. Accurate nodal staging is pivotal for treatment planning in early (stage I-II) oral c... more Background. Accurate nodal staging is pivotal for treatment planning in early (stage I-II) oral cancer. Unfortunately, current imaging modalities lack sensitivity to detect occult nodal metastases. Chromosomal region 11q13, including genes CCND1, Fas-associated death domain (FADD), and CTTN, is often amplified in oral cancer with nodal metastases. However, evidence in predicting occult nodal metastases is limited. Methods. In 158 patients with early tongue and floor of mouth (FOM) squamous cell carcinomas, both CCND1 amplification and cyclin D1, FADD, and cortactin protein expression were correlated with occult nodal metastases. Results. CCND1 amplification and cyclin D1 expression correlated with occult nodal metastases. Cyclin D1 expression was validated in an independent multicenter cohort, confirming the correlation with occult nodal metastases in early FOM cancers. Conclusion. Cyclin D1 is a predictive biomarker for occult nodal metastases in early FOM cancers. Prospective research on biopsy material should confirm these results before implementing its use in routine clinical practice. V
There is an ongoing debate about the value of (neo-)adjuvant chemotherapy in high- and intermedia... more There is an ongoing debate about the value of (neo-)adjuvant chemotherapy in high- and intermediate-grade osteosarcoma of the head and neck. All records of patients older than 16 years diagnosed with osteosarcoma of the head and neck in the Netherlands between 1993 and 2013 were reviewed. We identified a total of 77 patients with an osteosarcoma of the head and neck; the 5-year overall survival (OS) was 55%. In 50 patients with surgically resected high- or intermediate-grade osteosarcoma of the head and neck younger than 75 years, univariate and multivariable analysis, adjusting for age and resection margins, showed that patients who had not received chemotherapy had a significantly higher risk of local recurrence (hazard ratio [HR] = 3.78 and 3.66, respectively). In patients younger than 75 years of age with surgically resected high- and intermediate-grade osteosarcoma of the head and neck, treatment with (neo-)adjuvant chemotherapy resulted in a significantly smaller risk of local...
To compare cumulative cisplatin dose and toxicity between patients who received 3-weekly versus w... more To compare cumulative cisplatin dose and toxicity between patients who received 3-weekly versus weekly cisplatin during adjuvant radiotherapy for high-risk head and neck squamous cell carcinoma (HNSCC). Consecutive HNSCC patients with involved resection margins and/or extra-capsular extension in two tertiary cancer centers with different institutional practices were identified. Cumulative cisplatin dose was calculated and information on toxicity reviewed and compared between patients who received 3-weekly versus weekly cisplatin. Of 270 high risk patients, 60 received 3-weekly 100mg/m(2) and 48 received weekly 50mg/m(2) cisplatin during adjuvant radiotherapy (60-66Gy in 30-33 fractions). Fourteen patients received other chemotherapy schedules and 148 received no chemotherapy. Mean cumulative cisplatin dose was 199.4mg/m(2) (standard error (SE) 5.4) in 3-weekly versus 239.8mg/m(2) (SE 11.0, P=0.001) in weekly treated patients. Cumulative cisplatin ⩾200mg/m(2) was given to 67.7% of pa...
Adult stem cells are often touted as therapeutic agents in the regenerative medicine field, howev... more Adult stem cells are often touted as therapeutic agents in the regenerative medicine field, however data detailing both the engraftment and functional capabilities of solid tissue derived human adult epithelial stem cells is scarce. Here we show the isolation of adult human salivary gland (SG) stem/progenitor cells and demonstrate at the single cell level in vitro self-renewal and differentiation into multilineage organoids. We also show in vivo functionality, long-term engraftment and functional restoration in a xenotransplantation model. Indeed, transplanted human salisphere-derived cells restored saliva production and greatly improved the regenerative potential of irradiated SGs. Further selection for c-Kit expression enriches for cells with enhanced regenerative potencies. Interestingly, interaction of transplanted cells with the recipient SG may also be involved in functional recovery. Thus, we show for the first time that salispheres cultured from human SGs contain stem/progen...
Background and Objective: Patients with multiple nonmelanoma skin cancers (NMSCs), like immunosup... more Background and Objective: Patients with multiple nonmelanoma skin cancers (NMSCs), like immunosuppressed or nevoid basal cell carcinomas, offer a therapeutic challenge. Photodynamic therapy (PDT) using the systemic photosensitizer meta-tetrahydroxyphenylchlorin (mTHPC) has the ability to treat multiple NMSCs up to a depth of 10 mm in a single session. These unique properties offer an attractive alternative to regular therapies (e.g., surgery or radiation) to these patients. Study Design: A systemic search was carried out that focused on the main clinical studies using mTHPC-PDT on NMSCs in humans. This review describes some of the basic principles of the treatment, the most effective treatment parameters as well as its possible adverse outcomes, which is illustrated with a short description of our own experiences using this treatment modality on four patients with multiple NMSCs. Results: To date, only four clinical studies have been published. It was demonstrated that mTHPC-PDT could be highly effective. On illuminating 1-2 days after drug administration, plasma drug levels were high and the tumor clearance rates were high (up to 100%), with relative few side effects and excellent cosmetic and functional outcomes. These results were obtained with a relatively low, patient friendly photosensitizer dose (0.04-0.05 mg/ kg) as skin photosensitivity was shorter after the procedure. Although the patients personally experienced consistently good cure rates, the healing times varied greatly between anatomical areas. The head and neck areas heal well with good cosmesis, while the lower leg and foot areas show delayed, at times compromised, healing with scarring. Conclusions: Although mTHPC-PDT is described in the literature as an interesting and promising therapeutic option, especially for multiple NMSCs, a randomized clinical trial is lacking and personal experiences warrant too much skepticism. With the recent introduction of the hedgehog pathway inhibitor vismodegib, mTHPC-PDT seems to be less suitable as a first line of treatment; it should be considered as a last resort therapy.
In the reconstruction of maxillary or mandibular continuity-defects of (dentate) patients, the mo... more In the reconstruction of maxillary or mandibular continuity-defects of (dentate) patients, the most favourable treatment goal is placement of implant retained crowns or bridges in a bone graft that reconstructs the defect. Proper implant positioning is often impaired by suboptimal placement of the bone graft. This case describes a new technique of a full digitally planned, immediate restoration, two step surgical approach for reconstruction of a mandibular defect using a free vascularized fibula graft with implants and a bridge. A 68-year old male developed osteoradionecrosis of the mandible. The resection, cutting and implant placement in the fibula were virtually planned. Cutting/drilling guides were 3D printed and the bridge was CAD/CAM milled. During the first surgery, 2 implants were placed in the fibula according the digital planning and the position of the implants was scanned using an intra oral optical scanner. During the second surgery, a bridge was placed on the implants ...
Pre-radiation dental screening of head-neck cancer patients aims to identify and eliminate oral f... more Pre-radiation dental screening of head-neck cancer patients aims to identify and eliminate oral foci of infection to prevent post-radiation oral problems. The evidence for the efficacy of dental screening is unclear. In this systematic review, we analyzed available evidence on the efficacy of pre-radiation elimination of oral foci of infection in preventing oral sequelae. A search was conducted (MEDLINE/EMBASE) for papers published up to May 2014. Papers on head-neck cancer patients subjected to pre-radiation dental screening, (chemo)radiation and oral follow-up were included. Of the 1770 identified papers, 20 studies fulfilled the inclusion criteria of which 17 were retrospective. A great heterogeneity in patient groups, dental screening techniques, definitions of oral foci of infection and techniques for eliminating foci was found. Most papers lacked essential details on how dental screening was performed and a clear definition of an oral focus of infection. The evidence for efficacy of elimination of oral foci of infection to prevent post-radiotherapy oral sequelae was inconclusive. Consequently, the efficacy of pre-radiation elimination of oral foci of infection remains unclear. No conclusions can be drawn about a definition of an oral focus of infection and whether pre-radiation elimination of these foci should be mandatory. We therefore suggest prospective studies with well-defined criteria for oral foci of infection, a clear description of which foci were eliminated and how, a detailed description of pre-radiation dental screening, clearly described patient and tumor characteristics, and a detailed dental history and dental status. Subsequently, oral problems that occur post-radiation should be systematically recorded.
Exposure of the distal internal carotid artery (ICA) during carotid endarterectomy (CEA) for anat... more Exposure of the distal internal carotid artery (ICA) during carotid endarterectomy (CEA) for anatomically high carotid bifurcations or distal occlu-sive disease requires specialized procedures in some cases. Presence of disease at or above the second cervical vertebrae may complicate an otherwise safe and well-tolerated procedure. Limited accessibility of the distal ICA has resulted in a variety of operative approaches to gain optimal exposure and control. 1-7 Mandibular subluxation (MS) has been recommended to facilitate distal dissection and to potentially reduce the incidence of cranial nerve palsies. 8-11 We have reviewed our experience with MS to determine a preferred method and to document results. Details of the surgical procedure are described. PATIENTS AND METHODS From 1985 to 1998, 10 patients underwent unilateral MS as an adjunct to carotid reconstruction.
Over the past decade, the demand for three-dimensional (3D) patient-specific (PS) modelling and s... more Over the past decade, the demand for three-dimensional (3D) patient-specific (PS) modelling and simulations has increased considerably; they are now widely available and generally accepted as part of patient care. However, the patient specificity of current PS designs is often limited to this patient-matched fit and lacks individual mechanical aspects, or parameters, that conform to the specific patient’s needs in terms of biomechanical acceptance. Most biomechanical models of the mandible, e.g., finite element analyses (FEA), often used to design reconstructive implants or total joint replacement devices for the temporomandibular joint (TMJ), make use of a literature-based (mean) simplified muscular model of the masticatory muscles. A muscle’s cross-section seems proportionally related to its maximum contractile force and can be multiplied by an intrinsic strength constant, which previously has been calculated to be a constant of 37 [N/cm2]. Here, we propose a contemporary method t...
Due to the introduction of three-dimensional (3D) technology in surgery, it has become possible t... more Due to the introduction of three-dimensional (3D) technology in surgery, it has become possible to preoperatively plan complex bone resections and reconstructions, (corrections and adjustments related to bones), from head to toe [...]
We present an articulatory synthesis framework for the synthesis and manipulation of oral cancer ... more We present an articulatory synthesis framework for the synthesis and manipulation of oral cancer speech for clinical decision making and alleviation of patient stress. Objective and subjective evaluations demonstrate that the framework has acceptable naturalness and is worth further investigation. A subsequent subjective vowel and consonant identification experiment showed that the articulatory synthesis system can manipulate the articulatory trajectories so that the synthesised speech reproduces problems present in the ground truth oral cancer speech.
Accurate mandible segmentation is significant in the field of maxillofacial surgery to guide clin... more Accurate mandible segmentation is significant in the field of maxillofacial surgery to guide clinical diagnosis and treatment and develop appropriate surgical plans. In particular, cone-beam computed tomography (CBCT) images with metal parts, such as those used in oral and maxillofacial surgery (OMFS), often have susceptibilities when metal artifacts are present such as weak and blurred boundaries caused by a high-attenuation material and a low radiation dose in image acquisition. To overcome this problem, this paper proposes a novel deep learning-based approach (SASeg) for automated mandible segmentation that perceives overall mandible anatomical knowledge. SASeg utilizes a prior shape feature extractor (PSFE) module based on a mean mandible shape, and recurrent connections maintain the continuity structure of the mandible. The effectiveness of the proposed network is substantiated on a dental CBCT dataset from orthodontic treatment containing 59 patients. The experiments show that...
Accurate segmentation of the mandible from cone-beam computed tomography (CBCT) scans is an impor... more Accurate segmentation of the mandible from cone-beam computed tomography (CBCT) scans is an important step for building a personalized 3D digital mandible model for maxillofacial surgery and orthodontic treatment planning because of the low radiation dose and short scanning duration. CBCT images, however, exhibit lower contrast and higher levels of noise and artifacts due to extremely low radiation in comparison with the conventional computed tomography (CT), which makes automatic mandible segmentation from CBCT data challenging. In this work, we propose a novel coarse-to-fine segmentation framework based on 3D convolutional neural network and recurrent SegUnet for mandible segmentation in CBCT scans. Specifically, the mandible segmentation is decomposed into two stages: localization of the mandible-like region by rough segmentation and further accurate segmentation of the mandible details. The method was evaluated using a dental CBCT dataset. In addition, we evaluated the proposed ...
Three-dimensional technology is increasingly being used in acetabular fracture treatment. No syst... more Three-dimensional technology is increasingly being used in acetabular fracture treatment. No systematic reviews are available about the added clinical value of 3D-assisted acetabular fracture surgery compared to conventional surgery. Therefore, this study aimed to investigate whether 3D-assisted acetabular fracture surgery compared to conventional surgery improves surgical outcomes in terms of operation time, intraoperative blood loss, intraoperative fluoroscopy usage, complications, and postoperative fracture reduction, and whether it improves physical functioning. Pubmed and Embase databases were searched for articles on 3D technologies in acetabular fracture surgery, published between 2010 and February 2021. The McMaster critical review form was used to assess the methodological quality. Differences between 3D-assisted and conventional surgery were evaluated using the weighted mean and odds ratios. Nineteen studies were included. Three-dimensional-assisted surgery resulted in sig...
Due to the complex anatomical shape of the pelvis, screw placement can be challenging in acetabul... more Due to the complex anatomical shape of the pelvis, screw placement can be challenging in acetabular fracture surgery. This study aims to assess the accuracy of screw placement using patient-specific surgical drilling guides applied to pre-contoured conventional implants in acetabular fracture surgery. CT scans were made of four human cadavers to create 3D models of each (unfractured) pelvis. Implants were pre-contoured on 3D printed pelvic models and optically scanned. Following virtual preoperative planning, surgical drilling guides were designed to fit on top of the implant and were 3D printed. The differences between the pre-planned and actual screw directions (degrees) and screw entry points (mm) were assessed from the pre- and postoperative CT-scans. The median difference between the planned and actual screw direction was 5.9° (IQR: 4–8°) for the in-plate screws and 7.6° (IQR: 6–10°) for the infra-acetabular and column screws. The median entry point differences were 3.6 (IQR: 2...
6016Background: Salivary Duct Carcinoma (SDC) is a rare, highly aggressive subtype of salivary gl... more 6016Background: Salivary Duct Carcinoma (SDC) is a rare, highly aggressive subtype of salivary gland cancer, which is androgen receptor (AR) positive in most pts. In recurrent disease androgen deprivation therapy (ADT) can be used, however only limited data are available. The aim of this study was to evaluate clinical outcome, to identify prognostic factors for overall survival (OS) and to retrospectively analyze efficacy of ADT. Methods: The nationwide network and registry of histo- and cytopathology (PALGA) identified all adult pts with SDC between 1990 - 2014 in the Netherlands. Lymph node ratio (LNR) was defined as the number of positive LN divided by the total number of LN after neck dissection. Survival analyses were conducted using Kaplan-Meier method. The Cox proportional hazard model was used to identify prognostic factors on uni- and multivariable analyses. Results: A total of 157 pts with SDC were identified. Median age was 66 years, 77% were male. AR and HER2neu were positive in 100% and 44%, ...
Journal of the National Comprehensive Cancer Network, 2018
Background: Monitoring and effectively improving oncologic integrated care requires dashboard inf... more Background: Monitoring and effectively improving oncologic integrated care requires dashboard information based on quality registrations. The dashboard includes evidence-based quality indicators (QIs) that measure quality of care. This study aimed to assess the quality of current integrated head and neck cancer care with QIs, the variation between Dutch hospitals, and the influence of patient and hospital characteristics. Methods: Previously, 39 QIs were developed with input from medical specialists, allied health professionals, and patients' perspectives. QI scores were calculated with data from 1,667 curatively treated patients in 8 hospitals. QIs with a sample size of >400 patients were included to calculate reliable QI scores. We used multilevel analysis to explain the variation. Results: Current care varied from 29% for the QI about a case manager being present to discuss the treatment plan to 100% for the QI about the availability of a treatment plan. Variation between hospitals was small for the QI about patients discussed in multidisciplinary team meetings (adherence: 95%, range 88%-98%), but large for the QI about malnutrition screening (adherence: 50%, range 2%-100%). Higher QI scores were associated with lower performance status, advanced tumor stage, and tumor in the oral cavity or oropharynx at the patient level, and with more curatively treated patients (volume) at hospital level. Conclusions: Although the quality registration was only recently launched, it already visualizes hospital variation in current care. Four determinants were found to be influential: tumor stage, performance status, tumor site, and volume. More data are needed to assure stable results for use in quality improvement.
Current Opinion in Otolaryngology & Head & Neck Surgery, 2018
Purpose of review This review describes the advances in 3D virtual planning for mandibular and ma... more Purpose of review This review describes the advances in 3D virtual planning for mandibular and maxillary reconstruction surgical defects with full prosthetic rehabilitation. The primary purpose is to provide an overview of various techniques that apply 3D technology safely in primary and secondary reconstructive cases of patients suffering from head and neck cancer. Recent findings Methods have been developed to overcome the problem of control over the margin during surgery while the crucial decision with regard to resection margin and planning of osteotomies were predetermined by virtual planning. The unlimited possibilities of designing patient-specific implants can result in creative uniquely applied solutions for single cases but should be applied wisely with knowledge of biomechanical engineering principles.
Background. Accurate nodal staging is pivotal for treatment planning in early (stage I-II) oral c... more Background. Accurate nodal staging is pivotal for treatment planning in early (stage I-II) oral cancer. Unfortunately, current imaging modalities lack sensitivity to detect occult nodal metastases. Chromosomal region 11q13, including genes CCND1, Fas-associated death domain (FADD), and CTTN, is often amplified in oral cancer with nodal metastases. However, evidence in predicting occult nodal metastases is limited. Methods. In 158 patients with early tongue and floor of mouth (FOM) squamous cell carcinomas, both CCND1 amplification and cyclin D1, FADD, and cortactin protein expression were correlated with occult nodal metastases. Results. CCND1 amplification and cyclin D1 expression correlated with occult nodal metastases. Cyclin D1 expression was validated in an independent multicenter cohort, confirming the correlation with occult nodal metastases in early FOM cancers. Conclusion. Cyclin D1 is a predictive biomarker for occult nodal metastases in early FOM cancers. Prospective research on biopsy material should confirm these results before implementing its use in routine clinical practice. V
There is an ongoing debate about the value of (neo-)adjuvant chemotherapy in high- and intermedia... more There is an ongoing debate about the value of (neo-)adjuvant chemotherapy in high- and intermediate-grade osteosarcoma of the head and neck. All records of patients older than 16 years diagnosed with osteosarcoma of the head and neck in the Netherlands between 1993 and 2013 were reviewed. We identified a total of 77 patients with an osteosarcoma of the head and neck; the 5-year overall survival (OS) was 55%. In 50 patients with surgically resected high- or intermediate-grade osteosarcoma of the head and neck younger than 75 years, univariate and multivariable analysis, adjusting for age and resection margins, showed that patients who had not received chemotherapy had a significantly higher risk of local recurrence (hazard ratio [HR] = 3.78 and 3.66, respectively). In patients younger than 75 years of age with surgically resected high- and intermediate-grade osteosarcoma of the head and neck, treatment with (neo-)adjuvant chemotherapy resulted in a significantly smaller risk of local...
To compare cumulative cisplatin dose and toxicity between patients who received 3-weekly versus w... more To compare cumulative cisplatin dose and toxicity between patients who received 3-weekly versus weekly cisplatin during adjuvant radiotherapy for high-risk head and neck squamous cell carcinoma (HNSCC). Consecutive HNSCC patients with involved resection margins and/or extra-capsular extension in two tertiary cancer centers with different institutional practices were identified. Cumulative cisplatin dose was calculated and information on toxicity reviewed and compared between patients who received 3-weekly versus weekly cisplatin. Of 270 high risk patients, 60 received 3-weekly 100mg/m(2) and 48 received weekly 50mg/m(2) cisplatin during adjuvant radiotherapy (60-66Gy in 30-33 fractions). Fourteen patients received other chemotherapy schedules and 148 received no chemotherapy. Mean cumulative cisplatin dose was 199.4mg/m(2) (standard error (SE) 5.4) in 3-weekly versus 239.8mg/m(2) (SE 11.0, P=0.001) in weekly treated patients. Cumulative cisplatin ⩾200mg/m(2) was given to 67.7% of pa...
Adult stem cells are often touted as therapeutic agents in the regenerative medicine field, howev... more Adult stem cells are often touted as therapeutic agents in the regenerative medicine field, however data detailing both the engraftment and functional capabilities of solid tissue derived human adult epithelial stem cells is scarce. Here we show the isolation of adult human salivary gland (SG) stem/progenitor cells and demonstrate at the single cell level in vitro self-renewal and differentiation into multilineage organoids. We also show in vivo functionality, long-term engraftment and functional restoration in a xenotransplantation model. Indeed, transplanted human salisphere-derived cells restored saliva production and greatly improved the regenerative potential of irradiated SGs. Further selection for c-Kit expression enriches for cells with enhanced regenerative potencies. Interestingly, interaction of transplanted cells with the recipient SG may also be involved in functional recovery. Thus, we show for the first time that salispheres cultured from human SGs contain stem/progen...
Background and Objective: Patients with multiple nonmelanoma skin cancers (NMSCs), like immunosup... more Background and Objective: Patients with multiple nonmelanoma skin cancers (NMSCs), like immunosuppressed or nevoid basal cell carcinomas, offer a therapeutic challenge. Photodynamic therapy (PDT) using the systemic photosensitizer meta-tetrahydroxyphenylchlorin (mTHPC) has the ability to treat multiple NMSCs up to a depth of 10 mm in a single session. These unique properties offer an attractive alternative to regular therapies (e.g., surgery or radiation) to these patients. Study Design: A systemic search was carried out that focused on the main clinical studies using mTHPC-PDT on NMSCs in humans. This review describes some of the basic principles of the treatment, the most effective treatment parameters as well as its possible adverse outcomes, which is illustrated with a short description of our own experiences using this treatment modality on four patients with multiple NMSCs. Results: To date, only four clinical studies have been published. It was demonstrated that mTHPC-PDT could be highly effective. On illuminating 1-2 days after drug administration, plasma drug levels were high and the tumor clearance rates were high (up to 100%), with relative few side effects and excellent cosmetic and functional outcomes. These results were obtained with a relatively low, patient friendly photosensitizer dose (0.04-0.05 mg/ kg) as skin photosensitivity was shorter after the procedure. Although the patients personally experienced consistently good cure rates, the healing times varied greatly between anatomical areas. The head and neck areas heal well with good cosmesis, while the lower leg and foot areas show delayed, at times compromised, healing with scarring. Conclusions: Although mTHPC-PDT is described in the literature as an interesting and promising therapeutic option, especially for multiple NMSCs, a randomized clinical trial is lacking and personal experiences warrant too much skepticism. With the recent introduction of the hedgehog pathway inhibitor vismodegib, mTHPC-PDT seems to be less suitable as a first line of treatment; it should be considered as a last resort therapy.
In the reconstruction of maxillary or mandibular continuity-defects of (dentate) patients, the mo... more In the reconstruction of maxillary or mandibular continuity-defects of (dentate) patients, the most favourable treatment goal is placement of implant retained crowns or bridges in a bone graft that reconstructs the defect. Proper implant positioning is often impaired by suboptimal placement of the bone graft. This case describes a new technique of a full digitally planned, immediate restoration, two step surgical approach for reconstruction of a mandibular defect using a free vascularized fibula graft with implants and a bridge. A 68-year old male developed osteoradionecrosis of the mandible. The resection, cutting and implant placement in the fibula were virtually planned. Cutting/drilling guides were 3D printed and the bridge was CAD/CAM milled. During the first surgery, 2 implants were placed in the fibula according the digital planning and the position of the implants was scanned using an intra oral optical scanner. During the second surgery, a bridge was placed on the implants ...
Pre-radiation dental screening of head-neck cancer patients aims to identify and eliminate oral f... more Pre-radiation dental screening of head-neck cancer patients aims to identify and eliminate oral foci of infection to prevent post-radiation oral problems. The evidence for the efficacy of dental screening is unclear. In this systematic review, we analyzed available evidence on the efficacy of pre-radiation elimination of oral foci of infection in preventing oral sequelae. A search was conducted (MEDLINE/EMBASE) for papers published up to May 2014. Papers on head-neck cancer patients subjected to pre-radiation dental screening, (chemo)radiation and oral follow-up were included. Of the 1770 identified papers, 20 studies fulfilled the inclusion criteria of which 17 were retrospective. A great heterogeneity in patient groups, dental screening techniques, definitions of oral foci of infection and techniques for eliminating foci was found. Most papers lacked essential details on how dental screening was performed and a clear definition of an oral focus of infection. The evidence for efficacy of elimination of oral foci of infection to prevent post-radiotherapy oral sequelae was inconclusive. Consequently, the efficacy of pre-radiation elimination of oral foci of infection remains unclear. No conclusions can be drawn about a definition of an oral focus of infection and whether pre-radiation elimination of these foci should be mandatory. We therefore suggest prospective studies with well-defined criteria for oral foci of infection, a clear description of which foci were eliminated and how, a detailed description of pre-radiation dental screening, clearly described patient and tumor characteristics, and a detailed dental history and dental status. Subsequently, oral problems that occur post-radiation should be systematically recorded.
Exposure of the distal internal carotid artery (ICA) during carotid endarterectomy (CEA) for anat... more Exposure of the distal internal carotid artery (ICA) during carotid endarterectomy (CEA) for anatomically high carotid bifurcations or distal occlu-sive disease requires specialized procedures in some cases. Presence of disease at or above the second cervical vertebrae may complicate an otherwise safe and well-tolerated procedure. Limited accessibility of the distal ICA has resulted in a variety of operative approaches to gain optimal exposure and control. 1-7 Mandibular subluxation (MS) has been recommended to facilitate distal dissection and to potentially reduce the incidence of cranial nerve palsies. 8-11 We have reviewed our experience with MS to determine a preferred method and to document results. Details of the surgical procedure are described. PATIENTS AND METHODS From 1985 to 1998, 10 patients underwent unilateral MS as an adjunct to carotid reconstruction.
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Papers by Max Witjes