Franck Jegoux

Radiation effects on bone healing and reconstruction: interpretation of the literature

OBJECTIVE Reconstructing irradiated mandibles with biomaterials is still a challenge but little investigated. We collected data that could help us understand studies in the field of regeneration with biomaterials and irradiated bone. STUDY DESIGN Systematic review of the literature. RESULTS Delay and duration of radiation delivery and total equivalent dose are the most variable parameters in the various studies, resulting in confusion when interpreting the literature. Most reproducible experiments show that radiation reduces osteogenic cell numbers, alters cytokine capacity, and delays and damages bone remodeling. Interindividual variations and how such changes become irreversible lesions are still uncertain. In the case of regeneration using biomaterials, most studies have addressed the question of reconstruction in previously irradiated bone. The results show that osseointegration is often possible, although the failure rate is higher. The sooner the implantation takes place after the end of the radiation, the higher the likelihood of failure. Few studies have focused on primary reconstruction followed by early irradiation, and most of the currently available engineering models would be altered by radiation. Good outcomes have been obtained with bone morphogenetic protein and with total bone marrow transplanation. CONCLUSION This review points out the difficulties in achieving reproducible experiments and interpreting literature in this underinvestigated field.

Pattern of lateral neck metastases in N0 papillary thyroid carcinoma

BackgroundIndication and extent of lateral prophylactic neck dissection (PLND) in papillary thyroid carcinoma (PTC) is very controversial.MethodsWe retrospectively analysed 131 patients who underwent thyroidectomy and prophylactic lateral neck dissection from level II to V for PTC.Results140 PLND were performed. The occult lymph node metastases (OLNM) overall rate was 18.6%. The incidence of node involvement was 10% at level III and 6.4% at level IIa. Level IV and level Vb were both concerned by 5.7% OLNM. Only 2.9% of level IIb contained OLNM. None of the level Va ND revealed OLNM.ConclusionsOLNM from PTC occurs commonly in level IIa, III, IV and Vb. Incidence in other levels is low. For surgeons that usually perform PLND, we believe that a selective neck dissection of levels IIa, III, IV and Vb in N0 neck PTC is sufficient for the clearance of occult metastases.

Mandibular Segmental Defect Regenerated With Macroporous Biphasic Calcium Phosphate, Collagen Membrane, and Bone Marrow Graft in Dogs

OBJECTIVE To reconstruct segmental mandibulectomy using calcium phosphate ceramics and collagen membrane with a delayed bone marrow grafting in experimental animals. DESIGN Defects of segmental mandibulectomy were filled with calcium phosphate granules and wrapped with a collagen membrane in 4 dogs and left empty as a control in 2 dogs. Two months later, a bone marrow graft was injected into the center of the implants. Animals were humanely killed after a 16-week delay. SUBJECTS Six adult beagles were included in this study. INTERVENTION Segmental mandibulectomy. MAIN OUTCOME MEASURE Bone ingrowth and material resorption in the reconstructed segment. RESULTS Successful osseous colonization bridged the whole length of the defects. The good new bone formation at the center and the periosteum-like formation at the periphery suggest the osteoinductive role of the bone marrow graft and the healing scaffold role of the membrane. CONCLUSIONS This model succeeded in regenerating a large segmental defect in the mandible. An investigation with a postimplantation radiation delivery schedule is required with the use of this model, which should be considered as a preclinical study for a bone tissue engineering approach in patients with cancer-related bone defects.

Reconstruction of irradiated bone segmental defects with a biomaterial associating MBCP+®, microstructured collagen membrane and total bone marrow grafting: An experimental study in rabbits

The bone tissue engineering models used today are still a long way from any oncologic application as immediate postimplantation irradiation would decrease their osteoinductive potential. The aim of this study was to reconstruct a segmental critical size defect in a weight-bearing bone irradiated after implantation. Six white New Zealand rabbits were immediately implanted with a biomaterial associating resorbable collagen membrane EZ(R) filled and micro-macroporous biphasic calcium phosphate granules (MBCP+(R)). After a daily schedule of radiation delivery, and within 4 weeks, a total autologous bone marrow (BM) graft was injected percutaneously into the center of the implant. All the animals were sacrificed at 16 weeks. Successful osseous colonization was found to have bridged the entire length of the defects. Identical distribution of bone ingrowth and residual ceramics at the different levels of the implant suggests that the BM graft plays an osteoinductive role in the center of the defect. Periosteum-like formation was observed at the periphery, with the collagen membrane most likely playing a role. This model succeeded in bridging a large segmental defect in weight-bearing bone with immediate postimplantation fractionated radiation delivery. This has significant implications for the bone tissue engineering approach to patients with cancer-related bone defects.

Reconstruction of circumferential pharyngolaryngectomy using a 'horseshoe-shaped' pectoralis major myocutaneous flap.

Eighteen patients underwent a circumferential pharyngolaryngectomy reconstruction post pharyngolaryngectomy. All tumours showed pharyngo-oesophageal junction invasion or circular involvement of the hypopharynx, requiring total, circumferential pharyngolaryngectomy. A pectoralis major myocutaneous flap was directly sutured to the pre-vertebral fascia. A Montgomery salivary bypass tube was introduced into the oesophagus, and a nasogastric tube was placed within it. No post-operative complications occurred for 14 patients and only minor ones for the other four. Average post-operative stay was 12 days. For 15 patients, feeding returned to normal throughout the follow-up period. No fistulae were noted and neopharyngeal stenosis occurred in three patients (16 per cent). Thirteen had complete resection with normal margins. Thirteen were still alive after one to three years of follow up. The local recurrence rate was 16 per cent. The use of a pectoralis major myocutaneous flap with Sprianos technique provides a simple, reliable method for circumferential hypopharyngeal resection. It has been applied to a wide range of patients, especially elderly ones and those with poor general status, as well as to cases in which widespread involvement was detected during surgery.

Occult lymph node metastases increase locoregional recurrence in differentiated thyroid carcinoma.

Objectives: The impact of occult lymph node metastasis (OLNM) on locoregional recurrence (LRR) and survival in patients with N0 differentiated thyroid carcinoma is unclear, because no large study has been carried out. A retrospective study was conducted in our department to assess the influence of OLNM. Methods: We included 201 patients treated by prophylactic neck dissection for N0 differentiated thyroid carcinoma between 1974 and 2006. The incidence of OLNM and predictive factors for recurrence and survival were assessed. Results: The incidence of OLNM was 20%. Necks were involved at levels VI, III, II, IV, V, and I, in decreasing order of frequency. After a mean follow-up of 9 years, the rate of LRR was 8.9% and the rate of distant metastasis was 3.4%. An age of greater than 55 years and the presence of OLNM were predictive factors for LRR. An age of greater than 55 years and the presence of LRR were predictive factors for distant metastasis. The presence of distant metastasis was the only factor that significantly and independently influenced the disease-specific survival. Conclusions: We found that OLNM occurred in only 20% of N0 patients. The presence and especially the number of OLNMs on neck dissection were major risk factors for LRR in this study, but did not affect the disease-specific survival.

Development of a three-dimensional model for rapid evaluation of bone substitutes in vitro: effect of the 45S5 bioglass.

The evaluation of innovative bone substitutes requires the development of an optimal model close to physiological conditions. An interesting alternative is the use of an immortalized cell line to construct multicellular spheroids, that is, three-dimensional (3D) cultures. In this study, a modified hanging drops method has resulted in the generation of spheroids with a well-established human fetal osteoblasts line (hFOB 1.19), and tests have been focused on the effect of 45S5 bioglass ionic dissolution products in comparison with two-dimensional (2D) cultures. Depending on cell culture type, quantitative analysis (cell proliferation, viability/cytotoxicity, and cellular cycle) and qualitative analysis (electron microscopy and genes expression) showed a differential effect. Cell proliferation was enhanced in 2D-conditioned cultures in accordance with literature data, but decreased in 3D cultures submitted to the same conditions, without change of gene expression patterns. The decrease of cell proliferation, observed in conditioned spheroids, appears to be in agreement with clinical observations showing the insufficiency of commercially available bioglasses for bone repairing within nonbearing sites, such as periodontal defects or small bone filling, in general. Therefore, we suggest that this model could be adapted to the screening of innovative bioactive materials by laboratory techniques already available and extended monitoring of their bioactivity.

Results after u-shaped pectoralis major myocutaneous flap reconstruction of circumferential pharyngeal defects†‡

To evaluate surgical, functional, carcinologic results after circumferential pharyngolaryngectomy and reconstruction with U‐shaped pectoralis major myocutaneous flap.

Alveolar ridge augmentation in irradiated rabbit mandibles

Oral carcinomas are frequently treated with a nonsegmental mandibulectomy plus radiotherapy. Improving the quality of life of these patients depends on the possibilities for dental rehabilitation. The aim of this study was to increase the alveolar ridge height. Twelve white New Zealand rabbits underwent surgery to produce a 11 x 9 x 7 mm(3) horizontal bicortical full-thickness defect at the alveolar ridge of the left mandible. Six were implanted with a composite associating resorbable collagen membrane filled with micro-macroporous biphasic calcium phosphate granules. After a daily radiation delivery schedule for 4 weeks, a total autologous bone marrow graft was injected percutaneously into the center of the implant. All animals were sacrificed at 16 weeks. Successful osseous colonization was observed in all implants. Significant ridge augmentation was observed (p = 0.0349) in the implanted group compared with the control group. This study contributed to producing an experimental model for oncological mandible defects in rabbits.

Computed tomography in TN stage evaluation of oral cavity and oropharyngeal cancers

Oral and oropharyngeal carcinomas are characterized by a high incidence of node metastatic involvement and local extension. The study compared the TN stage of patients by clinical and computed tomography (CT) examination to postoperative histopathology. Sensitivity of CT for tumor extension was 82%, predictive value for bone involvement 67%. Clinical examination was poor in predicting the presence (54%) or absence (56%) of node involvement. Sensitivity of CT for assessment of node involvement was 80%, specificity 71%, positive predictive value 67%, and negative 83%. Node involvement was high (30%) in clinically NO necks versus only 9% for negative CT.