Ron Koole

Cell-Based Bone Tissue Engineering

The authors review the available data on bone tissue engineering and discuss possible new research areas that could help to make bone tissue engineering a clinical success.

Cell based bone tissue engineering in jaw defects.

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).

Preoperative Evaluation of Patients With Primary Head and Neck Cancer Using Dual-Head 18Fluorodeoxyglucose Positron Emission Tomography

OBJECTIVE To evaluate the value of 18fluorodeoxyglucose (FDG) positron emission tomography (PET) in primary head and neck cancer. BACKGROUND DATA Head and neck carcinomas tend to metastasize to regional lymph nodes rather than to spread hematogenously. With nodal metastases, cure rates decrease by approximately 50%. Moreover, in approximately 3% of the patients, a second primary tumor is found at initial presentation. METHODS Fifty-four consecutive patients (31 men and 23 women; mean age 60 years, range 34-81 years) with previously untreated squamous cell carcinomas of the oral cavity or oropharynx were studied. Before surgery and within a period of 3 weeks, clinical examination, chest x-ray, computed tomography (CT), ultrasonography with fine-needle aspiration cytology (US/ FNAC), and FDG-PET were performed. All study results were scored per neck side and were also classified as 0 (no metastases), 1 (single metastasis), or 2 (multiple metastases). RESULTS The sensitivity for the detection of lymph node metastases per neck side was 96%, 85%, and 64% for FDG-PET, CT, and US/FNAC, respectively. The specificity was 90%, 86%, and 100% for FDG-PET, CT, and US/FNAC, respectively. In terms of the classification, FDG-PET showed the best correlation with the histologic data. Finally, in nine patients (17%), a second primary tumor was detected by FDG-PET and confirmed by histologic evaluation. CONCLUSION Because of the high prevalence of second primary tumors detected by FDG-PET and the decreased error rate in the assessment of lymph node involvement compared with CT and US, FDG-PET should be routinely performed in patients with primary head and neck cancer.

Nonvascularized Bone Grafts for Segmental Reconstruction of the Mandible—A Reappraisal

PURPOSE To evaluate the success rate and complications of segmental mandibular reconstructions with autogenous nonvascularized iliac crest bone grafts, and to refine treatment strategies. PATIENTS AND METHODS Seventy-four patients with segmental mandibular defects were included. Malignant lesion, immediate reconstruction, smoking habit, radiotherapy, site of the defect, surgical approach, and method of graft fixation were analyzed as factors of influence on success. Success was defined as maintenance of bone continuity and stability, and absence of infection 1 year after reconstruction upon clinical and radiographic examination. Complications were divided into recipient and donor-site complications and classified as minor or major. The reconstruction was considered functionally complete if prosthetic rehabilitation was accomplished or if there was a sufficient remaining dentition for mastication. RESULTS In 56 (76%) patients, the initial reconstruction was successful. Multivariate analyses showed that symphyseal involvement (SI) and intraoral approach (IA) were significantly associated with failure (P(SI) = .022, P(IA) = .038) and major recipient-site complications (P(SI) = .022, P(IA) = .038). Thirty-two (43%) patients showed complications in the first postoperative year: 27 recipient-site complications and 6 donor-site complications. Nineteen (70%) recipient-site complications were classified as major. The reconstruction was functionally complete in 48 (86%) of the 56 patients with a successful initial reconstruction. CONCLUSIONS Nonvascularized iliac crest bone grafts for segmental reconstruction of the mandible is the method of choice on the condition that the defect is truly lateral and only an extraoral approach is used. In these cases, microvascular tissue transfer is not necessary.

Survival analysis of head and neck squamous cell carcinoma: Influence of smoking and drinking

Head and neck squamous cell carcinomas (HNSCCs) are associated with tobacco and alcohol; however, the prognostic relevance of these substances is unclear.

Free Vascularized Flaps for Reconstruction of the Mandible: Complications, Success, and Dental Rehabilitation

PURPOSE To evaluate complications and success of mandibular reconstruction with free fibula flaps, iliac crest flaps, and forearm flaps with reconstruction plates and to evaluate dental rehabilitation after these reconstructions. PATIENTS AND METHODS Eighty-three patients with segmental mandibular defects were included. Correlation analyses were used to determine the relationship between reconstruction type and clinical parameters with recipient-site complications and success. The dental rehabilitation was evaluated in successfully reconstructed survivors. RESULTS Multivariate analyses showed significant correlations between flap type and success (P < .0001). Of the patients, 51 (61%) were alive 2 years after the reconstruction. Mandibular reconstruction with a free forearm flap and reconstruction plate was associated with higher complication rates at the recipient site and higher failure rates compared with reconstruction with free vascularized bone flaps. Of the 32 successfully reconstructed survivors, 14 (44%) had a complete dental rehabilitation, of which 10 had dental implants and 4 did not. Only 6 (29%) of the edentulous survivors ultimately had an implant-supported prosthesis. CONCLUSIONS Reconstruction of the mandible with a free vascularized bone flap is superior to reconstruction with a free forearm flap with a reconstruction plate. Complete dental rehabilitation was reached in fewer than half of the surviving patients.

Quantitative dynamic contrast-enhanced MRI for the assessment of mandibular invasion by squamous cell carcinoma

The objective of this study was to determine the value of dynamic contrast-enhanced MRI (DCE-MRI) for the preoperative assessment of mandibular invasion in squamous cell carcinomas (SCC), adjacent or fixed to the mandible. DCE-MRI was performed with gadolinium diethylene triamine pentaacetic acid (Gd-DTPA). Data were obtained from 25 patients. From pharmacokinetic analysis of the tissue uptake of Gd-DTPA, the DCE-MRI parameters (k(ep), K(trans) and v(e)) were determined, with k(ep) representing the exchange rate constant, K(trans) the volume transfer constant and v(e) the volume of extracellular space per unit volume of tissue. The histology of the resection specimens was used as gold standard for the extent of mandibular invasion. SCC with medullary invasion showed higher mean k(ep) and K(trans) compared with SCC without medullary invasion (ANOVA, p<0.001). ROC analysis of k(ep) and K(trans) revealed reliable threshold values for medullary invasion. In conclusion, DCE-MRI can discriminate SCC with medullary invasion from SCC without medullary invasion and may serve as a valuable tool in preoperative tumour staging with regard to the delineation of medullary invasion.

Oral Function After Oncological Intervention in the Oral Cavity: A Retrospective Study

PURPOSE To assess self-perceived oral function of patients with oral cavity cancer at different stages of treatment, ie, before oncologic intervention, 5 weeks after intervention, and 5 years after intervention. PATIENTS AND METHODS A cohort of 158 patients with malignancy in the oral cavity treated by surgery in 1999 or 2000 was included. From this cohort we interviewed 69 patients by telephone in 2005 and collected data on dental status, disorders of chewing and swallowing, xerostomia, preference of food consistency, tube nutrition, weight loss, and speech for different stages of treatment. RESULTS For patients treated in the maxilla region we observed a significant (P < .05) recovery of perceived chewing ability after 5 years to the level experienced before oncologic intervention. Patients treated in the mandible region reported a deteriorated dental state, chewing ability, lip competence, and xerostomia after 5 years. Patients treated in the tongue and mouth-floor region experienced deterioration for dental state, chewing ability, and xerostomia after 5 years compared with the level before the oncologic intervention. CONCLUSIONS Our telephone interview on oral function provided supplementary information on how patients experienced their problems with oral function during various phases of oncologic treatment. A retrospective interview may thus help to add information to incomplete retrospective data.

Long-term effect of a nurse-led psychosocial intervention on health-related quality of life in patients with head and neck cancer: a randomised controlled trial

Background:Head and neck cancer (HNC) patients are prone to have a poor health-related quality of life after cancer treatment. This study investigated the effect of the nurse counselling and after intervention (NUCAI) on the health-related quality of life and depressive symptoms of HNC patients between 12 and 24 months after cancer treatment.Methods:Two hundred and five HNC patients were randomly allocated to NUCAI (N=103) or usual care (N=102). The 12-month nurse-led NUCAI is problem-focused and patient-driven and aims to help HNC patients manage with the physical, psychological and social consequences of their disease and its treatment. Health-related quality of life was evaluated with the EORTC QLQ-C30 and QLQ H&N35. Depressive symptoms were evaluated with the CES-D.Results:At 12 months the intervention group showed a significant (P<0.05) improvement in emotional and physical functioning, pain, swallowing, social contact, mouth opening and depressive symptoms. At 18 months, global quality of life, role and emotional functioning, pain, swallowing, mouth opening and depressive symptoms were significantly better in the intervention group than in the control group, and at 24 months emotional functioning and fatigue were significantly better in the intervention group.Conclusion:The NUCAI effectively improved several domains of health-related quality of life and depressive symptoms in HNC patients and would seem a promising intervention for implementation in daily clinical practice.

One-Year Effect of a Nurse-Led Psychosocial Intervention on Depressive Symptoms in Patients With Head and Neck Cancer: A Randomized Controlled Trial

BACKGROUND Many patients with head and neck cancer (HNC) experience depressive symptoms after treatment. This randomized controlled trial investigated the effects of a psychosocial nurse counseling and after intervention (NUCAI) versus usual care on the depressive and HNC-related physical symptoms of patients with HNC at 1 year after diagnosis. METHODS A total of 205 patients with HNC were randomly assigned to either intervention (n = 103) or usual care (n = 102), with stratification for gender and tumor stage. The NUCAI, which consisted of six bimonthly 45-minute counseling sessions, was a problem-focused intervention aimed at helping patients to manage the physical, psychological, and social consequences of HNC and its treatment. It was nurse-led and offered in combination with regular medical follow-up visits at the University Medical Center Utrecht, the Netherlands. Depressive symptoms at 1 year after diagnosis were the primary outcome. Analyses were performed on an intention-to-treat basis for the total sample and for a predefined subgroup of patients with raised levels of depressive symptoms (Center for Epidemiologic Studies-Depression score ≥ 12; n = 91) at baseline using mixed-effect models. RESULTS One year after HNC treatment, levels of depressive symptoms were significantly lower in the intervention group than in the control group in the total sample and in the subgroup of patients with raised levels of depressive symptoms. CONCLUSION The NUCAI was feasible and effective in reducing depressive symptoms in patients with HNC 1 year after HNC treatment, and especially in patients with raised levels of depressive symptoms. The results of this study need to be confirmed in future studies before the NUCAI can be used in daily clinical practice.