Ron Koole - Academia.edu (original) (raw)

Papers by Ron Koole

Research paper thumbnail of Midfacial growth and dental arch relationships in bilateral cleft palate following secondary alveolar bone grafting and orthodontic intervention: Factors predicting a Le Fort I osteotomy at age 18

Journal of Cranio-Maxillofacial Surgery

Research paper thumbnail of Early and late complications in the reconstructed mandible with free fibula flaps

Journal of Surgical Oncology

Background and Objectives: Evaluation of mandibular reconstructions with free fibula flaps. Ident... more Background and Objectives: Evaluation of mandibular reconstructions with free fibula flaps. Identification of factors associated with major recipient site complications, that is, necessitating surgical intervention under general anaesthesia. Methods: Seventy-nine reconstructions were included. The following factors were analyzed: fixation type, number of osteotomies, site of defect (bilateral/unilateral), surgeon, sex, ASA classification, continuous smoking, pathological N-stage, age, defect size, flap ischemic time, and postoperative radiotherapy. Proportional hazards regression was used to test the effect on the time between reconstruction and intervention. Results: Sixty-nine (87%) of the 79 fibula flaps were successful at the last follow-up. Forty-eight major recipient site complications occurred in 41 reconstructions. Nineteen complications required surgical intervention within six weeks and were mostly vascular problems, necessitating immediate intervention. These early complications were associated with defects crossing the midline, with an estimated relative risk of 5.3 (CI 1.1-20, P = 0.01). Twenty-nine complications required surgical intervention more than 6 weeks after the reconstruction. These late complications generally occurred after months or years, and were associated with smoking, with an estimated relative risk of 2.8 (CI 1.0-8.3, P = 0.05). Conclusions: Fibula flaps crossing the midline have a higher risk of early major recipient site complications than unilateral reconstructions. Smoking increases the risk of late complications. K E Y W O R D S early complications, free fibula flap, oral cancer, late complications, major recipient site complications, mandibular reconstruction This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Research paper thumbnail of Factors influencing neck and shoulder function after oral oncology treatment: a five-year prospective cohort study in 113 patients

Supportive Care in Cancer

Background The aim of this study was to identify factors influencing shoulder and/or neck functio... more Background The aim of this study was to identify factors influencing shoulder and/or neck function in patients up to five years after treatment. Materials and methods Lateral flexion of the neck, ipsilateral forward flexion, and abduction of the shoulder were measured. Potential factors were entered into a linear mixed model analysis to create a multivariate model for describing the results. Results Predicted neck and shoulder function was negatively influenced by higher age before intervention. Contralateral flexion of the neck was lower for patients undergoing surgery and radiotherapy compared to surgery. Ipsilateral flexion of the neck is influenced by a higher age at baseline. Ipsilateral shoulder abduction is lower for female gender, bone graft/flap reconstruction, and more extensive neck dissection. Ipsilateral forward flexion of the shoulder is lower for bone graft/flap reconstruction and better for patients with a T2 tumor in comparison to T3 and T4 tumors, as predicted. Conclusion By our five-year follow-up outcomes of this study, neck and/or shoulder impairments can be found for high-risk patients by physiotherapists.

Research paper thumbnail of Cathepsin K associates with lymph node metastasis and poor prognosis in oral squamous cell carcinoma

BMC cancer, Jan 5, 2018

Lymph node metastasis (LNM) is a major determinant of prognosis and treatment planning of oral sq... more Lymph node metastasis (LNM) is a major determinant of prognosis and treatment planning of oral squamous cell carcinoma (OSCC). Cysteine cathepsins constitute a family of proteolytic enzymes with known role in the degradation of the extracellular matrix. Involvement in pathological processes, such as inflammation and cancer progression, has been proved. The aim of the study was to discover the clinicopathological and prognostic implications of cathepsin K (CTSK) expression in oral squamous cell carcinoma. Eighty-three patients with primary OSCC, treated surgically between 1996 and 2000, were included. Gene expression data were acquired from a previously reported study. Human papilloma virus (HPV) status was previously determined by an algorithm for HPV-16. CTSK Protein expression was semi-quantitatively determined by immunohistochemistry in tumor and stromal cells. Expression data were correlated with various clinicopathological variables. Elevated gene and protein expression of CTSK...

Research paper thumbnail of A Distress Thermometer Intervention for Patients With Head and Neck Cancer


Oncology nursing forum, 2018

To investigate the feasibility of an intervention using the National Comprehensive Cancer Network... more To investigate the feasibility of an intervention using the National Comprehensive Cancer Network Distress Thermometer and Problem List with nurse-guided follow-up and the effect on depressive symptoms, health-related quality of life, and worry of cancer in patients with head and neck cancer. . 110 patients with head and neck cancer in a two-arm randomized, controlled trial in an outpatient clinic of a university hospital. . Patients were randomized to usual care (n = 57) or the intervention group (n = 53), which consisted of screening with the Distress Thermometer and Problem List plus nurse-guided follow-up lasting about 20 minutes three to four times during 12 months. Intention-to-treat analysis was performed using linear mixed models with outcomes at 6 and 12 months and baseline adjustment. . The intervention showed moderate compliance and acceptable session duration. Intervention participants were satisfied with nurses' care. Depressive symptoms, health-related quality of ...

Research paper thumbnail of O49. Down-regulation of SERPINB13 expression in head and neck squamous cell carcinomas associates with poor clinical outcome

Research paper thumbnail of Costs and clinical outcomes of implant placement during ablative surgery and postponed implant placement in curative oral oncology: a five-year retrospective cohort study

Clinical oral implants research, Jan 2, 2017

The aim of this study was to compare costs and clinical outcomes of two protocols for implant pla... more The aim of this study was to compare costs and clinical outcomes of two protocols for implant placement in edentulous oral cancer patients: implant placement during ablative surgery and postponed implant placement. All edentulous patients who underwent curative tumor surgery between 2007 and 2009 at the Radboud university medical center (Radboudumc) and UMC Utrecht, both in the Netherlands, were included retrospectively. At the Radboudumc, 79 of 98 patients received implants during ablative surgery. At the UMC Utrecht, 18 of 95 patients received implants after a disease-free period of at least 6 months, because satisfying conventional dentures could not be made. Costs, implant details and clinical outcomes were recorded retrospectively up to 5 years after tumor surgery. Individual costs of implant placement were lower in the during-ablative-surgery protocol (€2235 vs. €4152), while implant failure and loading were comparable to the postponed-placement protocol. In the during-ablativ...

Research paper thumbnail of Long-Term Follow-Up Study of Young Adults Treated for Unilateral Complete Cleft Lip, Alveolus, and Palate by a Treatment Protocol Including Two-Stage Palatoplasty: Speech Outcomes

Archives of plastic surgery, 2017

No consensus exists on the optimal treatment protocol for orofacial clefts or the optimal timing ... more No consensus exists on the optimal treatment protocol for orofacial clefts or the optimal timing of cleft palate closure. This study investigated factors influencing speech outcomes after two-stage palate repair in adults with a non-syndromal complete unilateral cleft lip and palate (UCLP). This was a retrospective analysis of adult patients with a UCLP who underwent two-stage palate closure and were treated at our tertiary cleft centre. Patients ≥17 years of age were invited for a final speech assessment. Their medical history was obtained from their medical files, and speech outcomes were assessed by a speech pathologist during the follow-up consultation. Forty-eight patients were included in the analysis, with a mean age of 21 years (standard deviation, 3.4 years). Their mean age at the time of hard and soft palate closure was 3 years and 8.0 months, respectively. In 40% of the patients, a pharyngoplasty was performed. On a 5-point intelligibility scale, 84.4% received a score of...

Research paper thumbnail of A novel semi-automatic segmentation protocol for volumetric assessment of alveolar cleft grafting procedures

Journal of Cranio-Maxillofacial Surgery, 2017

A novel protocol for volumetric assessment of alveolar cleft grafting procedures is presented. El... more A novel protocol for volumetric assessment of alveolar cleft grafting procedures is presented. Eleven cone-beam computed tomography (CBCT) datasets of patients who underwent secondary alveolar cleft reconstructive surgery for a unilateral alveolar cleft were evaluated by two investigators. Residual bone volumes 1 year after surgery were analysed using a semi-automated technique in which preoperative CBCT datasets were superimposed on the postoperative scans using voxel-based registration. To define the correct boundaries of the alveolar cleft defect in the preoperative CBCT dataset, a mirror image of the preoperative CBCT dataset was superimposed on the preoperative CBCT dataset. For the difference in residual bone volume between the two observers, an intraclass correlation of 0.98 and a Dice coefficient of 0.89 were found. This study describes a reliable segmentation protocol for volumetric analysis of the alveolar cleft defect in patients with a unilateral alveolar cleft.

Research paper thumbnail of Amplification and protein overexpression of cyclin D1: Predictor of occult nodal metastasis in early oral cancer

Head & Neck, 2016

Accurate nodal staging is pivotal for treatment planning in early (stage I-II) oral cancer. Unfor... more 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. 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. 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. 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. © 2016 Wiley Periodicals, Inc. Head Neck 39: 326-333, 2017.

Research paper thumbnail of The transmandibular implant: A 13-year survey of its use

Research paper thumbnail of O83. Validation of an expression profile for prediction of lymph node metastasis from primary head and neck squamous cell carcinomas (HNSCC)

Oral Oncology Supplement, 2009

Cox regression analysis was performed to assess dependency of the various features, and correlate... more Cox regression analysis was performed to assess dependency of the various features, and correlates ascertained by logistic regression. Conclusion: Involvement of level IIB is infrequent and there is no demonstrable correlation of its involvement. Level IV appears to be involved only if more proximal basins are also involved, and there was no incidence of skip metastases. There is an observable trend towards tumours approximating the midline and oropharynx to metastasise bilaterally. The incidence of nodal metastases appears to increase with tumour thickness but this is not a consistent correlation.

Research paper thumbnail of Cell based bone tissue engineering in jaw defects

Biomaterials, 2008

In 6 patients the potency of bone tissue engineering to reconstruct jaw defects was tested. After... more In 6 patients the potency of bone tissue engineering to reconstruct jaw defects was tested. After a bone marrow aspirate was taken, stem cells were cultured, expanded and grown for 7 days on a bone substitute in an osteogenic culture medium to allow formation of a layer of extracellular bone matrix. At the end of the procedure, this viable bone substitute was not only re-implanted in the patient, but also simultaneously subcutaneously implanted in mice to prove its osteogenic potency. In all patients, a viable bone substitute was successfully constructed, which was proven by bone formation after subcutaneous implantation in mice (ectopic bone formation). However, the same construct was reluctant to form bone in patients with intra-oral osseous defects (orthotopic bone formation). Although biopsies, taken 4 months after reconstructing the intra-oral bone defect, showed bone formation in 3 patients, only in 1 patient bone formation was induced by the tissue-engineered construct. Although bone tissue engineering has proven its value in animal studies, extra effort is needed to make it a predictable method for reconstruction jaw defects in humans. To judge its benefit, it is important to differentiate between bone formation induced by cells from the border of the osseous defect (osteoconduction) in relation to bone matrix produced by the implanted cells (osteogenesis).

Research paper thumbnail of FGFR Family Members Protein Expression as Prognostic Markers in Oral Cavity and Oropharyngeal Squamous Cell Carcinoma

Molecular diagnosis & therapy, Aug 9, 2016

Fibroblast growth factor receptor family member proteins (FGFR1-4) have been identified as promis... more Fibroblast growth factor receptor family member proteins (FGFR1-4) have been identified as promising novel therapeutic targets and prognostic markers in a wide spectrum of solid tumors. The present study investigates the expression and prognostic value of four FGFR family member proteins in a large multicenter oral cavity squamous cell carcinoma (OCSCC) and oropharyngeal squamous cell carcinoma (OPSCC) cohort. Protein expression of FGFR1-4 was determined by immunohistochemistry on tissue microarrays containing 951 formalin-fixed paraffin embedded OCSCC and OPSCC tissues from the University Medical Center Utrecht and University Medical Center Groningen. Protein expression was correlated to overall survival using Cox regression models, and bootstrapping was performed as internal validation. FGFR proteins were highly expressed in 39-64 % of OCSCC and 63-79 % of OPSCC. Seventy-three percent (299/412) of OCSCC and 85 % (305/357) of OPSCC highly co-expressed two or more FGFR family member...

Research paper thumbnail of Complications in alveolar distraction osteogenesis of the atrophic mandible

Int J Oral Maxillofac Surg, 2007

To improve the starting point for placement of dental implants, 45 patients suffering from atroph... more To improve the starting point for placement of dental implants, 45 patients suffering from atrophied edentulous mandibles, with a vertical height varying between 7.3 and 15.8mm, were treated by alveolar vertical distraction osteogenesis (VDO). The mean follow-up period was 3 years, ranging from 1 to 7 years. Associated complications, as occurred during instalment of the distractor device, VDO period and consolidation phase, and also after dental implant placement, were evaluated. Observed complications were: early fractures (2%), late fractures (17%), bleeding or haematoma (4%), infections (6%), skin perforation (2%), mucosal dehiscence (8%), sensory disturbances (28%), sagging chin (13%) and failure of dental implants (13%). In 10 patients 2 complications and in 1 patient 3 complications were monitored. All complications occurred in the first year. It is concluded that VDO to restore vertical bone height in patients with mandibular atrophy is a surgically delicate technique with a high risk of various complications. The likelihood of the most striking complication, namely fracture occurrence, increases with decreasing residual bone height.

Research paper thumbnail of Functional benefits of implants placed during ablative surgery: A 5-year prospective study on the prosthodontic rehabilitation of 56 edentulous oral cancer patients

Head & Neck, 2016

The timing of placement as well as the functional benefit of interforaminal implants in edentulou... more The timing of placement as well as the functional benefit of interforaminal implants in edentulous patients treated for oral cancer is unclear. Fifty-six patients were recruited at 2 institutions. In 1 institution, interforaminal implants were placed during ablative surgery, the other institution used conventional prosthodontics with optional placement of implants postsurgery (postponed-placement). Masticatory performance, bite force, and subjective masticatory function were assessed before and 6 months, 1 year, and 5 years after surgery. Implant-retained overdentures (IODs) demonstrated the highest bite force and the least problems with solid food and food choice. Masticatory performance was equal for IODs and conventional dentures. After 5 years, IODs from patients in the during-ablative-surgery cohort tend to have higher bite force and masticatory performance than those from patients in the postponed-placement cohort. IODs produce the highest overall masticatory function. Implant placement during ablative surgery seems to be functionally beneficial. © 2016 Wiley Periodicals, Inc. Head Neck, 2016.

Research paper thumbnail of Fibroblast growth factor receptor 3 protein is overexpressed in oral and oropharyngeal squamous cell carcinoma

Cancer Medicine, 2015

Fibroblast growth factor receptor 3 (FGFR3) is a member of the fibroblast growth factor receptor ... more Fibroblast growth factor receptor 3 (FGFR3) is a member of the fibroblast growth factor receptor tyrosine kinase family. It has been identified as a promising therapeutic target in multiple types of cancer. We have investigated FGFR3 protein expression and FGFR3 gene copy-numbers in a single well-documented cohort of oral and oropharyngeal squamous cell carcinoma. Tissue microarray sets containing 452 formalin-fixed paraffin-embedded tissues were immunohistochemically stained with an anti-FGFR3 antibody and hybridized with a FGFR3 fluorescence in situ hybridization probe. FGFR3 protein expression was correlated with clinicopathological and survival data, which were retrieved from electronic medical records. FGFR3 mRNA data of 522 head and neck squamous cell carcinoma (HNSCC) were retrieved from The Cancer Genome Atlas (TCGA). Fibroblast growth factor receptor 3 (FGFR3) protein was overexpressed in 48% (89/185) of oral and 59% (124/211) of oropharyngeal squamous cell carcinoma. Overexpression of FGFR3 protein was not related to overall survival or diseasefree survival in oral (HR[hazard ratio]: 0.94; 95% CI: 0.64-1.39; P = 0.77, HR: 0.94; 95% CI: 0.65-1.36; P = 0.75) and oropharyngeal squamous cell carcinoma (HR: 1.21; 95% CI: 0.81-1.80; P = 0.36, HR: 0.42; 95% CI: 0.79-1.77; P = 0.42). FGFR3 mRNA was upregulated in 3% (18/522) of HNSCC from the TCGA. The FGFR3 gene was gained in 0.6% (1/179) of oral squamous cell carcinoma but no amplification was found in oral and oropharyngeal squamous cell carcinoma. In conclusion, FGFR3 protein is frequently overexpressed in oral and oropharyngeal squamous cell carcinoma. Therefore, it may serve as a potential therapeutic target for FGFR3-directed therapies in oral and oropharyngeal squamous cell carcinoma.

Research paper thumbnail of O.422 The effect of alar cinch sutures and VY-closure on soft tissue dynamics after le fort I osteotomy

J Cranio Maxillofac Surg, 2006

Research paper thumbnail of Jaarlijkse thoraxfoto bij patienten na behandeling wegens larynx- of een mondholtecarcinoom: slechts beperkt rendement ten aanzien van tweede primaire tumoren in de long

Research paper thumbnail of Preradiation dental extraction decisions in patients with head and neck cancer

Oral Surgery Oral Medicine Oral Pathology Oral Radiology and Endodontology, Oct 31, 1999

The first objectives of this international survey were to study how dental-related and radiothera... more The first objectives of this international survey were to study how dental-related and radiotherapy-related risk factors influence clinicians' preradiation dental decision making in patients with head and neck cancer and to evaluate clinicians' degree of certainty in making such decisions. A further objective was to examine the correlation of clinicians' policies with a policy based on a model for dental decision support that was presented in an earlier article. A consensus questionnaire was mailed to 54 oral-maxillofacial surgeons and hospital-based dentists at a number of international locations. The responses were aggregated and anonymously analyzed through use of a multiple regression procedure. Forty-four clinicians returned the questionnaire (response rate, 81%). Nine clinicians (20%) were using printed clinical guidelines for preradiation dental screening. Eighty-eight percent of clinicians' preradiation decisions and 49% of their certainty could be explained by the studied risk factors. Not all risk factors were significant at P <.001. Clinicians' policies showed high correlation (.85) with the policy based on the model for dental decision support. The findings support our previous assumption that policies in this field seem to be based primarily on clinical experience and opinions rather than on evidence-based clinical guidelines. We conclude that the clinical usefulness and validity of the model for dental decision support should now be tested and that it could also serve as a training tool.

Research paper thumbnail of Midfacial growth and dental arch relationships in bilateral cleft palate following secondary alveolar bone grafting and orthodontic intervention: Factors predicting a Le Fort I osteotomy at age 18

Journal of Cranio-Maxillofacial Surgery

Research paper thumbnail of Early and late complications in the reconstructed mandible with free fibula flaps

Journal of Surgical Oncology

Background and Objectives: Evaluation of mandibular reconstructions with free fibula flaps. Ident... more Background and Objectives: Evaluation of mandibular reconstructions with free fibula flaps. Identification of factors associated with major recipient site complications, that is, necessitating surgical intervention under general anaesthesia. Methods: Seventy-nine reconstructions were included. The following factors were analyzed: fixation type, number of osteotomies, site of defect (bilateral/unilateral), surgeon, sex, ASA classification, continuous smoking, pathological N-stage, age, defect size, flap ischemic time, and postoperative radiotherapy. Proportional hazards regression was used to test the effect on the time between reconstruction and intervention. Results: Sixty-nine (87%) of the 79 fibula flaps were successful at the last follow-up. Forty-eight major recipient site complications occurred in 41 reconstructions. Nineteen complications required surgical intervention within six weeks and were mostly vascular problems, necessitating immediate intervention. These early complications were associated with defects crossing the midline, with an estimated relative risk of 5.3 (CI 1.1-20, P = 0.01). Twenty-nine complications required surgical intervention more than 6 weeks after the reconstruction. These late complications generally occurred after months or years, and were associated with smoking, with an estimated relative risk of 2.8 (CI 1.0-8.3, P = 0.05). Conclusions: Fibula flaps crossing the midline have a higher risk of early major recipient site complications than unilateral reconstructions. Smoking increases the risk of late complications. K E Y W O R D S early complications, free fibula flap, oral cancer, late complications, major recipient site complications, mandibular reconstruction This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Research paper thumbnail of Factors influencing neck and shoulder function after oral oncology treatment: a five-year prospective cohort study in 113 patients

Supportive Care in Cancer

Background The aim of this study was to identify factors influencing shoulder and/or neck functio... more Background The aim of this study was to identify factors influencing shoulder and/or neck function in patients up to five years after treatment. Materials and methods Lateral flexion of the neck, ipsilateral forward flexion, and abduction of the shoulder were measured. Potential factors were entered into a linear mixed model analysis to create a multivariate model for describing the results. Results Predicted neck and shoulder function was negatively influenced by higher age before intervention. Contralateral flexion of the neck was lower for patients undergoing surgery and radiotherapy compared to surgery. Ipsilateral flexion of the neck is influenced by a higher age at baseline. Ipsilateral shoulder abduction is lower for female gender, bone graft/flap reconstruction, and more extensive neck dissection. Ipsilateral forward flexion of the shoulder is lower for bone graft/flap reconstruction and better for patients with a T2 tumor in comparison to T3 and T4 tumors, as predicted. Conclusion By our five-year follow-up outcomes of this study, neck and/or shoulder impairments can be found for high-risk patients by physiotherapists.

Research paper thumbnail of Cathepsin K associates with lymph node metastasis and poor prognosis in oral squamous cell carcinoma

BMC cancer, Jan 5, 2018

Lymph node metastasis (LNM) is a major determinant of prognosis and treatment planning of oral sq... more Lymph node metastasis (LNM) is a major determinant of prognosis and treatment planning of oral squamous cell carcinoma (OSCC). Cysteine cathepsins constitute a family of proteolytic enzymes with known role in the degradation of the extracellular matrix. Involvement in pathological processes, such as inflammation and cancer progression, has been proved. The aim of the study was to discover the clinicopathological and prognostic implications of cathepsin K (CTSK) expression in oral squamous cell carcinoma. Eighty-three patients with primary OSCC, treated surgically between 1996 and 2000, were included. Gene expression data were acquired from a previously reported study. Human papilloma virus (HPV) status was previously determined by an algorithm for HPV-16. CTSK Protein expression was semi-quantitatively determined by immunohistochemistry in tumor and stromal cells. Expression data were correlated with various clinicopathological variables. Elevated gene and protein expression of CTSK...

Research paper thumbnail of A Distress Thermometer Intervention for Patients With Head and Neck Cancer


Oncology nursing forum, 2018

To investigate the feasibility of an intervention using the National Comprehensive Cancer Network... more To investigate the feasibility of an intervention using the National Comprehensive Cancer Network Distress Thermometer and Problem List with nurse-guided follow-up and the effect on depressive symptoms, health-related quality of life, and worry of cancer in patients with head and neck cancer. . 110 patients with head and neck cancer in a two-arm randomized, controlled trial in an outpatient clinic of a university hospital. . Patients were randomized to usual care (n = 57) or the intervention group (n = 53), which consisted of screening with the Distress Thermometer and Problem List plus nurse-guided follow-up lasting about 20 minutes three to four times during 12 months. Intention-to-treat analysis was performed using linear mixed models with outcomes at 6 and 12 months and baseline adjustment. . The intervention showed moderate compliance and acceptable session duration. Intervention participants were satisfied with nurses' care. Depressive symptoms, health-related quality of ...

Research paper thumbnail of O49. Down-regulation of SERPINB13 expression in head and neck squamous cell carcinomas associates with poor clinical outcome

Research paper thumbnail of Costs and clinical outcomes of implant placement during ablative surgery and postponed implant placement in curative oral oncology: a five-year retrospective cohort study

Clinical oral implants research, Jan 2, 2017

The aim of this study was to compare costs and clinical outcomes of two protocols for implant pla... more The aim of this study was to compare costs and clinical outcomes of two protocols for implant placement in edentulous oral cancer patients: implant placement during ablative surgery and postponed implant placement. All edentulous patients who underwent curative tumor surgery between 2007 and 2009 at the Radboud university medical center (Radboudumc) and UMC Utrecht, both in the Netherlands, were included retrospectively. At the Radboudumc, 79 of 98 patients received implants during ablative surgery. At the UMC Utrecht, 18 of 95 patients received implants after a disease-free period of at least 6 months, because satisfying conventional dentures could not be made. Costs, implant details and clinical outcomes were recorded retrospectively up to 5 years after tumor surgery. Individual costs of implant placement were lower in the during-ablative-surgery protocol (€2235 vs. €4152), while implant failure and loading were comparable to the postponed-placement protocol. In the during-ablativ...

Research paper thumbnail of Long-Term Follow-Up Study of Young Adults Treated for Unilateral Complete Cleft Lip, Alveolus, and Palate by a Treatment Protocol Including Two-Stage Palatoplasty: Speech Outcomes

Archives of plastic surgery, 2017

No consensus exists on the optimal treatment protocol for orofacial clefts or the optimal timing ... more No consensus exists on the optimal treatment protocol for orofacial clefts or the optimal timing of cleft palate closure. This study investigated factors influencing speech outcomes after two-stage palate repair in adults with a non-syndromal complete unilateral cleft lip and palate (UCLP). This was a retrospective analysis of adult patients with a UCLP who underwent two-stage palate closure and were treated at our tertiary cleft centre. Patients ≥17 years of age were invited for a final speech assessment. Their medical history was obtained from their medical files, and speech outcomes were assessed by a speech pathologist during the follow-up consultation. Forty-eight patients were included in the analysis, with a mean age of 21 years (standard deviation, 3.4 years). Their mean age at the time of hard and soft palate closure was 3 years and 8.0 months, respectively. In 40% of the patients, a pharyngoplasty was performed. On a 5-point intelligibility scale, 84.4% received a score of...

Research paper thumbnail of A novel semi-automatic segmentation protocol for volumetric assessment of alveolar cleft grafting procedures

Journal of Cranio-Maxillofacial Surgery, 2017

A novel protocol for volumetric assessment of alveolar cleft grafting procedures is presented. El... more A novel protocol for volumetric assessment of alveolar cleft grafting procedures is presented. Eleven cone-beam computed tomography (CBCT) datasets of patients who underwent secondary alveolar cleft reconstructive surgery for a unilateral alveolar cleft were evaluated by two investigators. Residual bone volumes 1 year after surgery were analysed using a semi-automated technique in which preoperative CBCT datasets were superimposed on the postoperative scans using voxel-based registration. To define the correct boundaries of the alveolar cleft defect in the preoperative CBCT dataset, a mirror image of the preoperative CBCT dataset was superimposed on the preoperative CBCT dataset. For the difference in residual bone volume between the two observers, an intraclass correlation of 0.98 and a Dice coefficient of 0.89 were found. This study describes a reliable segmentation protocol for volumetric analysis of the alveolar cleft defect in patients with a unilateral alveolar cleft.

Research paper thumbnail of Amplification and protein overexpression of cyclin D1: Predictor of occult nodal metastasis in early oral cancer

Head & Neck, 2016

Accurate nodal staging is pivotal for treatment planning in early (stage I-II) oral cancer. Unfor... more 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. 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. 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. 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. © 2016 Wiley Periodicals, Inc. Head Neck 39: 326-333, 2017.

Research paper thumbnail of The transmandibular implant: A 13-year survey of its use

Research paper thumbnail of O83. Validation of an expression profile for prediction of lymph node metastasis from primary head and neck squamous cell carcinomas (HNSCC)

Oral Oncology Supplement, 2009

Cox regression analysis was performed to assess dependency of the various features, and correlate... more Cox regression analysis was performed to assess dependency of the various features, and correlates ascertained by logistic regression. Conclusion: Involvement of level IIB is infrequent and there is no demonstrable correlation of its involvement. Level IV appears to be involved only if more proximal basins are also involved, and there was no incidence of skip metastases. There is an observable trend towards tumours approximating the midline and oropharynx to metastasise bilaterally. The incidence of nodal metastases appears to increase with tumour thickness but this is not a consistent correlation.

Research paper thumbnail of Cell based bone tissue engineering in jaw defects

Biomaterials, 2008

In 6 patients the potency of bone tissue engineering to reconstruct jaw defects was tested. After... more In 6 patients the potency of bone tissue engineering to reconstruct jaw defects was tested. After a bone marrow aspirate was taken, stem cells were cultured, expanded and grown for 7 days on a bone substitute in an osteogenic culture medium to allow formation of a layer of extracellular bone matrix. At the end of the procedure, this viable bone substitute was not only re-implanted in the patient, but also simultaneously subcutaneously implanted in mice to prove its osteogenic potency. In all patients, a viable bone substitute was successfully constructed, which was proven by bone formation after subcutaneous implantation in mice (ectopic bone formation). However, the same construct was reluctant to form bone in patients with intra-oral osseous defects (orthotopic bone formation). Although biopsies, taken 4 months after reconstructing the intra-oral bone defect, showed bone formation in 3 patients, only in 1 patient bone formation was induced by the tissue-engineered construct. Although bone tissue engineering has proven its value in animal studies, extra effort is needed to make it a predictable method for reconstruction jaw defects in humans. To judge its benefit, it is important to differentiate between bone formation induced by cells from the border of the osseous defect (osteoconduction) in relation to bone matrix produced by the implanted cells (osteogenesis).

Research paper thumbnail of FGFR Family Members Protein Expression as Prognostic Markers in Oral Cavity and Oropharyngeal Squamous Cell Carcinoma

Molecular diagnosis & therapy, Aug 9, 2016

Fibroblast growth factor receptor family member proteins (FGFR1-4) have been identified as promis... more Fibroblast growth factor receptor family member proteins (FGFR1-4) have been identified as promising novel therapeutic targets and prognostic markers in a wide spectrum of solid tumors. The present study investigates the expression and prognostic value of four FGFR family member proteins in a large multicenter oral cavity squamous cell carcinoma (OCSCC) and oropharyngeal squamous cell carcinoma (OPSCC) cohort. Protein expression of FGFR1-4 was determined by immunohistochemistry on tissue microarrays containing 951 formalin-fixed paraffin embedded OCSCC and OPSCC tissues from the University Medical Center Utrecht and University Medical Center Groningen. Protein expression was correlated to overall survival using Cox regression models, and bootstrapping was performed as internal validation. FGFR proteins were highly expressed in 39-64 % of OCSCC and 63-79 % of OPSCC. Seventy-three percent (299/412) of OCSCC and 85 % (305/357) of OPSCC highly co-expressed two or more FGFR family member...

Research paper thumbnail of Complications in alveolar distraction osteogenesis of the atrophic mandible

Int J Oral Maxillofac Surg, 2007

To improve the starting point for placement of dental implants, 45 patients suffering from atroph... more To improve the starting point for placement of dental implants, 45 patients suffering from atrophied edentulous mandibles, with a vertical height varying between 7.3 and 15.8mm, were treated by alveolar vertical distraction osteogenesis (VDO). The mean follow-up period was 3 years, ranging from 1 to 7 years. Associated complications, as occurred during instalment of the distractor device, VDO period and consolidation phase, and also after dental implant placement, were evaluated. Observed complications were: early fractures (2%), late fractures (17%), bleeding or haematoma (4%), infections (6%), skin perforation (2%), mucosal dehiscence (8%), sensory disturbances (28%), sagging chin (13%) and failure of dental implants (13%). In 10 patients 2 complications and in 1 patient 3 complications were monitored. All complications occurred in the first year. It is concluded that VDO to restore vertical bone height in patients with mandibular atrophy is a surgically delicate technique with a high risk of various complications. The likelihood of the most striking complication, namely fracture occurrence, increases with decreasing residual bone height.

Research paper thumbnail of Functional benefits of implants placed during ablative surgery: A 5-year prospective study on the prosthodontic rehabilitation of 56 edentulous oral cancer patients

Head & Neck, 2016

The timing of placement as well as the functional benefit of interforaminal implants in edentulou... more The timing of placement as well as the functional benefit of interforaminal implants in edentulous patients treated for oral cancer is unclear. Fifty-six patients were recruited at 2 institutions. In 1 institution, interforaminal implants were placed during ablative surgery, the other institution used conventional prosthodontics with optional placement of implants postsurgery (postponed-placement). Masticatory performance, bite force, and subjective masticatory function were assessed before and 6 months, 1 year, and 5 years after surgery. Implant-retained overdentures (IODs) demonstrated the highest bite force and the least problems with solid food and food choice. Masticatory performance was equal for IODs and conventional dentures. After 5 years, IODs from patients in the during-ablative-surgery cohort tend to have higher bite force and masticatory performance than those from patients in the postponed-placement cohort. IODs produce the highest overall masticatory function. Implant placement during ablative surgery seems to be functionally beneficial. © 2016 Wiley Periodicals, Inc. Head Neck, 2016.

Research paper thumbnail of Fibroblast growth factor receptor 3 protein is overexpressed in oral and oropharyngeal squamous cell carcinoma

Cancer Medicine, 2015

Fibroblast growth factor receptor 3 (FGFR3) is a member of the fibroblast growth factor receptor ... more Fibroblast growth factor receptor 3 (FGFR3) is a member of the fibroblast growth factor receptor tyrosine kinase family. It has been identified as a promising therapeutic target in multiple types of cancer. We have investigated FGFR3 protein expression and FGFR3 gene copy-numbers in a single well-documented cohort of oral and oropharyngeal squamous cell carcinoma. Tissue microarray sets containing 452 formalin-fixed paraffin-embedded tissues were immunohistochemically stained with an anti-FGFR3 antibody and hybridized with a FGFR3 fluorescence in situ hybridization probe. FGFR3 protein expression was correlated with clinicopathological and survival data, which were retrieved from electronic medical records. FGFR3 mRNA data of 522 head and neck squamous cell carcinoma (HNSCC) were retrieved from The Cancer Genome Atlas (TCGA). Fibroblast growth factor receptor 3 (FGFR3) protein was overexpressed in 48% (89/185) of oral and 59% (124/211) of oropharyngeal squamous cell carcinoma. Overexpression of FGFR3 protein was not related to overall survival or diseasefree survival in oral (HR[hazard ratio]: 0.94; 95% CI: 0.64-1.39; P = 0.77, HR: 0.94; 95% CI: 0.65-1.36; P = 0.75) and oropharyngeal squamous cell carcinoma (HR: 1.21; 95% CI: 0.81-1.80; P = 0.36, HR: 0.42; 95% CI: 0.79-1.77; P = 0.42). FGFR3 mRNA was upregulated in 3% (18/522) of HNSCC from the TCGA. The FGFR3 gene was gained in 0.6% (1/179) of oral squamous cell carcinoma but no amplification was found in oral and oropharyngeal squamous cell carcinoma. In conclusion, FGFR3 protein is frequently overexpressed in oral and oropharyngeal squamous cell carcinoma. Therefore, it may serve as a potential therapeutic target for FGFR3-directed therapies in oral and oropharyngeal squamous cell carcinoma.

Research paper thumbnail of O.422 The effect of alar cinch sutures and VY-closure on soft tissue dynamics after le fort I osteotomy

J Cranio Maxillofac Surg, 2006

Research paper thumbnail of Jaarlijkse thoraxfoto bij patienten na behandeling wegens larynx- of een mondholtecarcinoom: slechts beperkt rendement ten aanzien van tweede primaire tumoren in de long

Research paper thumbnail of Preradiation dental extraction decisions in patients with head and neck cancer

Oral Surgery Oral Medicine Oral Pathology Oral Radiology and Endodontology, Oct 31, 1999

The first objectives of this international survey were to study how dental-related and radiothera... more The first objectives of this international survey were to study how dental-related and radiotherapy-related risk factors influence clinicians' preradiation dental decision making in patients with head and neck cancer and to evaluate clinicians' degree of certainty in making such decisions. A further objective was to examine the correlation of clinicians' policies with a policy based on a model for dental decision support that was presented in an earlier article. A consensus questionnaire was mailed to 54 oral-maxillofacial surgeons and hospital-based dentists at a number of international locations. The responses were aggregated and anonymously analyzed through use of a multiple regression procedure. Forty-four clinicians returned the questionnaire (response rate, 81%). Nine clinicians (20%) were using printed clinical guidelines for preradiation dental screening. Eighty-eight percent of clinicians' preradiation decisions and 49% of their certainty could be explained by the studied risk factors. Not all risk factors were significant at P <.001. Clinicians' policies showed high correlation (.85) with the policy based on the model for dental decision support. The findings support our previous assumption that policies in this field seem to be based primarily on clinical experience and opinions rather than on evidence-based clinical guidelines. We conclude that the clinical usefulness and validity of the model for dental decision support should now be tested and that it could also serve as a training tool.