Exploring Regorafenib Responsiveness and Uncovering Molecular Mechanisms in Recurrent Glioblastoma Tumors through Longitudinal In Vitro Sampling.

Glioblastoma, a deadly brain tumor, shows limited response to standard therapies like temozolomide (TMZ). Recent findings from the REGOMA trial underscore a significant survival improvement offered by Regorafenib (REGO) in recurrent glioblastoma. Our study aimed to propose a 3D ex vivo drug response precision medicine approach to investigate recurrent glioblastoma sensitivity to REGO and elucidate the underlying molecular mechanisms involved in tumor resistance or responsiveness to treatment. Three-dimensional glioblastoma organoids (GB-EXPs) obtained from 18 patients' resected recurrent glioblastoma tumors were treated with TMZ and REGO. Drug responses were evaluated using NAD(P)H FLIM, stratifying tumors as responders (Resp) or non-responders (NRs). Whole-exome sequencing was performed on 16 tissue samples, and whole-transcriptome analysis on 13 GB-EXPs treated and untreated. We found 35% (n = 9) and 77% (n = 20) of tumors responded to TMZ and REGO, respectively, with no instances of TMZ-Resp being REGO-NRs. Exome analysis revealed a unique mutational profile in REGO-Resp tumors compared to NR tumors. Transcriptome analysis identified distinct expression patterns in Resp and NR tumors, impacting Rho GTPase and NOTCH signaling, known to be involved in drug response. In conclusion, recurrent glioblastoma tumors were more responsive to REGO compared to TMZ treatment. Importantly, our approach enables a comprehensive longitudinal exploration of the molecular changes induced by treatment, unveiling promising biomarkers indicative of drug response.

O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET) PET as a potential selection tool for second surgery in glioblastoma patients.

BACKGROUND: Treatment-related changes still represent a diagnostic challenge in the management of patients with suspect of recurrent glioblastoma. The specificity of conventional MRI in detecting recurrence remains limited. Brain PET imaging provides information on tumor metabolism and can contribute to improving the diagnostic accuracy of cerebral neoplasms. We performed a retrospective analysis to evaluate the clinical value of O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET) PET in the diagnosis of glioblastoma recurrence. METHODS: A retrospective analysis on patients considered suitable for salvage surgery for recurrence glioblastoma was performed. 18F-FET-PET was performed to investigate gadolinium enhancement suspected for recurrence. Static and kinetic 18F-FET parameters were analyzed and related to O-6-methylguanine-DNA methyltransferase (MGMT) status. RESULTS: Forty-two of the 51 patients who underwent 18F-FET-PET were re-operated. In each case, neuropathological diagnosis of tumor recurrence was confirmed. pMGMT hypermethylation was detected in 21 patients. Mean tumor-to-brain ratios (TBR) max was 3.87 (range 2.6-6.0). Static and kinetic 18F-FET parameters were similar according to MGMT status. CONCLUSIONS: 18FET-PET can be a reliable tool to improve the selection of patients suitable for salvage surgery for glioblastoma recurrence.

Innovative Approach to Isolate and Characterize Glioblastoma Circulating Tumor Cells and Correlation with Tumor Mutational Status.

Circulating tumor cells (CTCs) are one of the most important causes of tumor recurrence and distant metastases. Glioblastoma (GBM) has been considered restricted to the brain for many years. Nevertheless, in the past years, several pieces of evidence indicate that hematogenous dissemination is a reality, and this is also in the caseof GBM. Our aim was to optimize CTCs' detection in GBM and define the genetic background of single CTCs compared to the primary GBM tumor and its recurrence to demonstrate that CTCs are indeed derived from the parental tumor. We collected blood samples from a recurrent IDH wt GBM patient. We genotyped the parental recurrent tumor tissue and the respective primary GBM tissue. CTCs were analyzed using the DEPArray system. CTCs Copy Number Alterations (CNAs) and sequencing analyses were performed to compare CTCs' genetic background with the same patient's primary and recurrent GBM tissues. We identified 210 common mutations in the primary and recurrent tumors. Among these, three somatic high-frequency mutations (in PRKCB, TBX1, and COG5 genes) were selected to investigate their presence in CTCs. Almost all sorted CTCs (9/13) had at least one of the mutations tested. The presence of TERT promoter mutations was also investigated and C228T variation was found in parental tumors and CTCs (C228T heterozygous and homozygous, respectively). We were able to isolate and genotype CTCs from a patient with GBM. We found common mutations but also exclusive molecular characteristics.

Metabolic-imaging of human glioblastoma live tumors: A new precision-medicine approach to predict tumor treatment response early.

Background: Glioblastoma (GB) is the most severe form of brain cancer, with a 12-15 month median survival. Surgical resection, temozolomide (TMZ) treatment, and radiotherapy remain the primary therapeutic options for GB, and no new therapies have been introduced in recent years. This therapeutic standstill is primarily due to preclinical approaches that do not fully respect the complexity of GB cell biology and fail to test efficiently anti-cancer treatments. Therefore, better treatment screening approaches are needed. In this study, we have developed a novel functional precision medicine approach to test the response to anticancer treatments in organoids derived from the resected tumors of glioblastoma patients. Methods: GB organoids were grown for a short period of time to prevent any genetic and morphological evolution and divergence from the tumor of origin. We chose metabolic imaging by NAD(P)H fluorescence lifetime imaging microscopy (FLIM) to predict early and non-invasively ex-vivo anti-cancer treatment responses of GB organoids. TMZ was used as the benchmark drug to validate the approach. Whole-transcriptome and whole-exome analyses were performed to characterize tumor cases stratification. Results: Our functional precision medicine approach was completed within one week after surgery and two groups of TMZ Responder and Non-Responder tumors were identified. FLIM-based metabolic tumor stratification was well reflected at the molecular level, confirming the validity of our approach, highlighting also new target genes associated with TMZ treatment and identifying a new 17-gene molecular signature associated with survival. The number of MGMT gene promoter methylated tumors was higher in the responsive group, as expected, however, some non-methylated tumor cases turned out to be nevertheless responsive to TMZ, suggesting that our procedure could be synergistic with the classical MGMT methylation biomarker. Conclusions: For the first time, FLIM-based metabolic imaging was used on live glioblastoma organoids. Unlike other approaches, ex-vivo patient-tailored drug response is performed at an early stage of tumor culturing with no animal involvement and with minimal tampering with the original tumor cytoarchitecture. This functional precision medicine approach can be exploited in a range of clinical and laboratory settings to improve the clinical management of GB patients and implemented on other cancers as well.

Single-Cell Molecular Characterization to Partition the Human Glioblastoma Tumor Microenvironment Genetic Background.

BACKGROUND: Glioblastoma (GB) is a devastating primary brain malignancy. The recurrence of GB is inevitable despite the standard treatment of surgery, chemotherapy, and radiation, and the median survival is limited to around 15 months. The barriers to treatment include the complex interactions among the different cellular components inhabiting the tumor microenvironment. The complex heterogeneous nature of GB cells is helped by the local inflammatory tumor microenvironment, which mostly induces tumor aggressiveness and drug resistance. METHODS: By using fluorescent multiple labeling and a DEPArray cell separator, we recovered several single cells or groups of single cells from populations of different origins from IDH-WT GB samples. From each GB sample, we collected astrocytes-like (GFAP+), microglia-like (IBA1+), stem-like cells (CD133+), and endothelial-like cells (CD105+) and performed Copy Number Aberration (CNA) analysis with a low sequencing depth. The same tumors were subjected to a bulk CNA analysis. RESULTS: The tumor partition in its single components allowed single-cell molecular subtyping which revealed new aspects of the GB altered genetic background. CONCLUSIONS: Nowadays, single-cell approaches are leading to a new understanding of GB physiology and disease. Moreover, single-cell CNAs resource will permit new insights into genome heterogeneity, mutational processes, and clonal evolution in malignant tissues.

Pulmonary Circulation on the Crossroads Between the Left and Right Heart in Systemic Sclerosis: A Clinical Challenge for Cardiologists and Rheumatologists.

Involvement of the right heart-pulmonary circulation system in systemic sclerosis is a typical feature, with critical prognostic implications. Pulmonary hypertension may occur in association with interstitial lung disease or as a result of an isolated pulmonary vascular disease that may affect both the precapillary arterioles and the postcapillary venules, as well as a consequence of left heart involvement. These apparently different phenotypes often underlie a significant pathophysiologic overlap, which makes the diagnosis and management of these patients highly complex and uncertain.

Augmentation of the floor of the maxillary sinus with recombinant human bone morphogenetic protein-7: a pilot radiological and histological study in humans.

The aim of this study was to evaluate the quantity and quality of bony regeneration after we had used recombinant human bone morphogenetic protein-7 (rhBMP-7 to augment the floor of the maxillary sinus. Nine consecutive patients with bilateral posterior maxillary atrophy who required augmentation of the sinus for interposition of implants were treated simultaneously with rhBMP-7 (Osigraft) with deproteinised bone substitute (0.5 g on the test side) and with deproteinised bone alone (2.0 g on the control side). Computed tomographic images preoperatively, immediately postoperatively, and at 4 months postoperatively showed a mean (SD) postoperative gain of 10.8 (3.0) mm on the test side and of 10.2 (1.8) mm on the control side. Histological and histomorphometric analyses of biopsy specimens showed that there was significantly more new bone on the control side (19.9 (6.8)%) than on the test side (6.6 (4.8)%). In this pilot controlled trial of the use of rhBMP-7, histological analyses showed that it resulted in the formation of less bone than treatment with inorganic bovine hydroxyapatite.

Immediate loading of dental implants placed in severely resorbed edentulous maxillae reconstructed with Le Fort I osteotomy and interpositional bone grafting.

BACKGROUND: Reconstruction and rehabilitation of atrophic maxillae with bone grafts is a lengthy and demanding procedure. This study reports the immediate loading of 50 implants placed on six extremely atrophied edentulous maxillae reconstructed with Le Fort I osteotomy and iliac bone grafting. METHODS: Six patients, aged 49 to 68 years, with severely atrophied maxillae were treated with Le Fort I osteotomy and iliac bone grafting to allow for implant-borne prosthetic rehabilitation. Four to 5 months thereafter, 50 implants (seven to 10 per patient) were placed in reconstructed maxillae and immediately functionally loaded with a screw-retained definitive prosthesis. The patients were followed by clinical and radiographic examinations for 24 months after prosthetic loading. RESULTS: The grafting procedure and healing period before implant placement were uneventful in all patients. Two implants were lost within 2 months after prosthesis insertion in two patients, with an overall survival rate of 96%. The prostheses success rate was 100%. At the end of the follow-up period, all remaining implants appeared clinically healthy; crestal bone loss was >1.7 mm for six implants, resulting in a cumulative success rate of 84%. CONCLUSION: Immediate loading of implants placed after Le Fort I osteotomy and interpositional iliac bone grafting could be considered a viable protocol to rehabilitate extremely atrophied edentulous maxillae, considerably reducing the treatment time.

Dose-dependent effect of adipose-derived adult stem cells on vertical bone regeneration in rabbit calvarium.

Previous in vivo studies have shown a limited potential for vertical bone regeneration using osteoconductive scaffolds alone. In the present study, we investigated whether the association of adipose-derived adult stem cells (ASCs) with anorganic bovine bone (ABB) scaffold improved bone formation and implant osseointegration in a vertical guided bone regeneration model. Two pre-formed titanium domes were placed on the calvaria of 12 rabbits. Four treatment modalities were evenly distributed among the 24 domes: ABB alone, and ABB containing 3 x 10(5), 3 x 10(6), or 3 x 10(7) cells/graft. After 1 month, the domes were removed and one titanium implant was placed into each augmented site. One month after the second operation, the animals were killed and biopsy specimens were examined by histomorphometric and micro-CT analyses. Results indicated that at all concentrations, the ASC-loaded groups showed significantly more new bone formation and higher mean values of bone-implant contact and bone density inside threads than the ABB group. Furthermore, ASCs demonstrated a dose-response relationship, with the highest dose chosen inducing more robust bone regeneration. This study suggests that the delivery of ASCs on ABB might effectively increase vertical bone regeneration and implant osseointegration, versus ABB alone.

Thoracic extradural haematoma after epidural anaesthesia.

The administration of analgesics to the thoracic spine is established practice in the operating room, minimizing the need for systemic anaesthetic administration during thoracic surgery. Complications arising from thoracic epidural anaesthesia are uncommon but potentially disastrous. Here, we report the case of a 43-year-old woman who developed a thoracic epidural haematoma with paraplegia a few hours after the removal of an epidural catheter. The patient underwent emergency thoracic laminectomy and clot evacuation. After a 4 months period, there was almost complete neurological recovery. Epidural haematoma is a rare complication that must be heeded and urgently treated in case of clinical deterioration after the epidural analgesia.

Immediate functional loading of dental implants supporting a bar-retained maxillary overdenture: preliminary 12-month results.

BACKGROUND: The present study evaluated the efficacy of a treatment consisting of placing and immediately loading implants with a bar-retained overdenture in edentulous maxillae. METHODS: Twenty-two consecutive patients were treated with four or five implants rigidly connected with a bar, which were then loaded with a maxillary overdenture within 48 hours post-surgery. The patients were followed clinically and radiographically for 1 year after loading. The implant outcome with regard to survival and success was analyzed. Visual analog scale questionnaires were used to record patient function and satisfaction before and after implant treatment. RESULTS: Of the 103 implants, three failed within 1 year. Two implants, although integrated, presented with marginal bone resorption (MBR) values higher than those proposed for successful implants. Cumulative survival and success rates of implants were 97.1% and 95.2%, respectively. The average MBR after 1 year was low (0.78 +/- 0.79 mm). The main prosthetic complication was the frequent need for complete relining of the prosthesis in the initial weeks after loading (27.2%). The questionnaire revealed a significant increase in all comfort, functional, and esthetic parameters (Friedman test; P <0.0001), except in the cleaning feasibility category; a significant decrease in satisfaction was observed in this category (Friedman test; P <0.05), indicating the difficulty patients had in maintaining a high level of oral hygiene. CONCLUSION: These preliminary results suggest that immediate loading of multiple implants supporting a bar-retained overdenture may represent a predictable treatment option for the rehabilitation of the edentulous maxilla.

Problems with dental implants that were placed on vertically distracted fibular free flaps after resection: a report of six cases.

We report the clinical outcome of dental implants placed on vertically distracted fibular free flaps that were used to reconstruct maxillary and mandibular defects after resection. Distraction osteogenesis (DO) of fibular free flaps was used for six patients (5 men, 1 woman) a mean of 19 months (range 11-38) after 5 mandibular and 1 maxillary reconstructions. A mean of 5 months (range 2-11) after removal of the distractor, 35 implants were inserted and loaded with implant-supported fixed prostheses. The mean (range) follow-up period was 39 (17-81) months. The course of the DO and the clinical and radiographic outcomes of the implants were assessed. Of six vertically distracted fibular free flaps, there was one case of vector lingual tipping during the consolidation phase and a fracture of the basal fibular cortex that necessitated additional grafting with iliac bone to stabilise the distracted area. The mean (range) vertical bone gain was 14 (12-15) mm. Four of 35 implants (11%) failed during the follow-up period. The mean peri-implant bone resorption was 2.5mm. Cumulative implant survival was 31/35 (89%) and survival after loading 31/33 (94%). Distraction osteogenesis of fibular free flaps caused a remarkable number of complications and pronounced resorption of bone around the implants, probably as a result of the formation of granulomatous tissue; a careful peri-implant follow-up and the maintenance of oral hygiene are essential.

Effect of mesenchymal stem cells and platelet-rich plasma on the healing of standardized bone defects in the alveolar ridge: a comparative histomorphometric study in minipigs.

PURPOSE: The purpose of this study was to test the effect of the combination of mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP) incorporated into a fluorohydroxyapatite (FHA) scaffold on bone regeneration in cylindrical defects in the edentulous mandibular ridge of minipigs. MATERIALS AND METHODS: Two mandibular premolar teeth were extracted bilaterally in 8 adult minipigs. After 2 months, 4 standardized defects of 3.5 mm diameter and 8 mm depth were created in each root site. The defects were randomly grafted with autogenous mandibular bone, FHA alone, PRP-FHA, or MSCs-PRP-FHA. A resorbable collagen membrane was placed over the defect area and the flaps were sutured. The animals were sacrificed 3 months later and biopsy samples were taken from the defect sites for histologic and histomorphometric assessment. RESULTS: There was no evidence of inflammation or adverse tissue reaction with either treatment. MSCs-PRP-FHA-treated sites showed new vital bone between residual grafting particles. PRP-FHA- and FHA-treated sites showed residual particles in a background of marrow soft tissue with a moderate quantity of newly formed bone. Autogenous bone (46.97%) and MSCs-PRP-FHA (45.28%) produced a significantly higher amount of vital bone than PRP-FHA (37.95%), or FHA alone (36.03%). Further, the MSCs-PRP-FHA-treated defects showed a significantly higher percentage of contact between graft particles and newly formed bone compared with PRP-FHA and FHA group (59.23% vs 48.37% and 46.43%, respectively). CONCLUSIONS: Our results suggest that, in this animal model, the addition of MSCs to PRP-FHA enhances bone formation after 3 months.

Evaluation of survival and success rates of dental implants placed at the time of or after alveolar ridge augmentation with an autogenous mandibular bone graft and titanium mesh: a 3- to 8-year retrospective study.

PURPOSE: The purpose of this retrospective longitudinal study was to evaluate the survival and success rates of 56 implants consecutively placed in alveolar ridges following a one- or two-stage augmentative procedure, using autogenous bone and titanium micromeshes. MATERIALS AND METHODS: This study included 24 consecutive patients treated with 27 micromeshes and mandibular particulated bone. In 13 patients, 20 implants were placed at the time of the reconstructive procedure. In the remaining 11 patients, 36 implants were positioned in a second surgery 8 to 9 months after grafting. Follow-up data (implant survival, success rate, marginal bone resorption) were collected after 3 to 8 years of prosthetic loading. RESULTS: Four of the 27 micromeshes (complication rate, 14.8%) were exposed prematurely and were removed before the intended time. The mean vertical bone augmentation obtained was 5.4 +/- 1.81 mm for implants placed in simultaneous procedures and 4.5 +/- 1.16 mm in delayed procedures. None of the 56 implants was lost during the observation period (cumulative implant survival rate, 100%). Radiographic analysis showed stable marginal bone levels, with a mean bone resorption of 1.58 +/- 0.48 mm after 3 to 8 years. Only two implants demonstrated increased bone loss (3.12 and 3.37 mm) over the follow-up period, whereas the remaining 54 implants were considered clinically successful, resulting in a cumulative success rate of 96.4%. CONCLUSIONS: This study revealed that implant placement in augmented ridges using micromeshes and autogenous bone provided satisfactory long-term survival and success rates, with minimal bone resorption.

Mesenchymal stem cells and platelet-rich plasma enhance bone formation in sinus grafting: a histomorphometric study in minipigs.

OBJECTIVES: Autologous, allogenic, and alloplastic materials for sinus augmentation have specific drawbacks, which has stimulated an ongoing search for new materials and tissue-engineering constructs. We investigated whether mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP) seeded on a fluorohydroxyapatite (FH) scaffold can improve bone formation and bone-to-implant contact (BIC) in maxillary sinus grafting. MATERIAL AND METHODS: Bilateral sinus augmentation procedures were performed in eight minipigs. MSCs, PRP, and FH scaffold (test site) or FH alone (control site) were grafted in each maxillary sinus. Distal to the osteotomy, one dental implant per sinus was placed in the grafting material through the facial sinus wall. The animals were killed 3 months after grafting, and block sections of the implant sites were harvested and prepared for histomorphometric analysis. RESULTS: After 12 weeks, a significant increase in bone formation occurred in the test sites compared with the control sites (42.51%versus 18.98%; p=0.001). In addition, BIC was significantly greater in the test sites compared with the control sites in the regenerated area (23.71%versus 6.63%; p=0.028). CONCLUSIONS: These findings show that sinus augmentation with MSCs-PRP, combined with FH may enhance bone formation and osseointegration of dental implants compared with FH alone in minipigs.

Exercise Doppler echocardiography identifies preclinic asymptomatic pulmonary hypertension in systemic sclerosis.

In systemic sclerosis (SSc), the involvement of the interstitium or vascular system of the lung may lead to pulmonary arterial hypertension (PAH). PAH is often asymptomatic or oligosymptomatic in early SSc and, when it becomes symptomatic, pulmonary vascular system is already damaged. Exercise echocardiography (ex-echo), measuring pulmonary artery pressure (PAP) during exercise and allowing to differentiate physiologic from altered PAP responses, may identify subclinical PAH. Our aims were (a) to evaluate by ex-echo the change of PAP in patients with SSc without lung involvement; and (b) to correlate PAP during exercise (ex-PAP) values to clinical and biohumoral parameters of PAH. Twenty-seven patients with limited SSc (ISSc) without interstitial lung involvement were studied. Patients underwent rest and exercise two-dimensional and Doppler echocardiography by supine cycloergometer. Systolic PAP was calculated using the maximum systolic velocity of the tricuspid regurgitant jet at rest and during exercise values of systolic PAP exceeding 40 mmHg at ex-echo were considered as abnormal, and biohumoral markers potentially related to PAH were assessed. Eighteen of 27 SSc patients presented an ex-PAP > 40 mmHg, while in 9 of 27 patients ex-PAP values remained < 40 mmHg (48.8 +/- 4.5 mmHg versus 36.2 +/- 3.1 mmHg; P < 0.001). Other echocardiographic and ergometric parameters, clinical tests, and biohumoral markers were not different in the two groups. Ex-PAP significantly correlated with D-dimer (P = 0.0125; r2 = 0.2029). Ex-echo identifies a cluster of SSc patients with subclinical PAH that may develop PAH. This group should be followed up and may be considered for specific therapies to prevent disease evolution.

Histologic and histomorphometric evaluation of alveolar ridge augmentation using bone grafts and titanium micromesh in humans.

BACKGROUND: Recently, the use of titanium micromesh for alveolar bone augmentation has drawn interest; however, only limited histologic data are available on the quality of the bone regenerated. Therefore, this study compared the use of 100% intraoral autogenous bone to a combination of intraoral autogenous bone (70%) and bovine porous bone mineral (BPBM) (30%) for alveolar ridge augmentation with titanium micromesh histologically and histomorphometrically. METHODS: Twelve partially edentulous patients required alveolar bone augmentation before implant insertion because of ridge resorption. The defect sites, six in the maxilla and six in the mandible, were reconstructed with particulate autologous bone (control group, N = 6) or a mixture of autologous bone and BPBM (test group, N = 6) in combination with titanium micromesh. Core biopsies were taken from the defect sites 8 to 9 months after grafting at the time of implant insertion. RESULTS: Newly formed compact bone with a well-organized lamellar pattern was identified in all specimens. In the samples taken from the test group, the BPBM particles were surrounded completely by newly formed bone with no signs of resorption. The mean total bone volume was 62.38% +/- 13.02% in the control group and 52.88% +/- 11.47% in the test group. The soft tissue volume was 37.61% +/- 13.02% and 29.96% +/- 12.58%, respectively, and the residual BPBM volume was 17.15% +/- 2.72% in the test group. No statistical difference was observed in the histologic parameters evaluated, irrespective of graft type and site (P >0.05). CONCLUSION: Within the limits of this study, BPBM (30%) in combination with autogenous bone (70%) did not yield a lower percentage of new bone formed compared to autogenous bone alone in ridge augmentation with titanium micromesh.

Impact of implant surface and grafting protocol on clinical outcomes of endosseous implants.

PURPOSE: The objectives of this study were to (1) evaluate the survival of implants placed in maxillary sinuses augmented with a 70:30 mixture of autogenous bone and anorganic bovine hydroxyapatite (Bio-Oss) at 1 and 5 years, (2) observe the difference in survival rate between 1-stage and 2-stage procedures, and (3) compare the survival rate of rough-surfaced implants with that of machined implants. MATERIALS AND METHODS: A total of 30 consecutively patients (48 sinuses) with Cawood and Howell Class V and VI atrophy were evaluated. Lateral osteotomy techniques were used in all cases. Implants were placed either simultaneous with grafting (1-stage procedure) or after a delay (2-stage procedure), depending on the amount of residual bone. A 70:30 mixture of autogenous bone and anorganic bovine hydroxyapatite was used as the graft material. All patients were followed up at 1 year after prosthetic loading, while a limited group of these patients was followed up to 5 years. RESULTS: In 8 patients where the residual crestal bone under the sinus floor assessed by computed tomography was at least 4.5 mm (mean, 5.3 mm), the 1-stage procedure was used for 11 sinus elevations and 32 implants. In 22 patients where the residual crestal bone was less than 4.5 mm (mean, 2.5 mm), the 2-stage procedure was used for 37 sinus elevations and 108 implants. For the 140 implants placed, the overall survival rate was 95.7% at the healing abutment surgery, and the cumulative survival rate was 94.9% at 1 and 5 years. The type of surgical technique was significantly associated with implant failure (P < .05); implants placed using the 1-stage procedure showed a failure rate of 12.5%, while implants placed with the 2-stage procedure had a failure rate of 2.8%. No significant difference in survival rate was observed with respect to implant surface. CONCLUSIONS: A high survival rate was achieved when sinus elevation was performed with a combination of autogenous bone and anorganic bovine hydroxyapatite, even where a minimal amount of residual crestal bone was present. The survival rate was improved when implants were placed after a healing period.

Alveolar distraction osteogenesis for bone augmentation of severely atrophic ridges in 10 consecutive cases: a histologic and histomorphometric study.

BACKGROUND: This study analyzed bone healing in surgically osteodistracted maxillary and mandibular ridges histologically and histomorphometrically at two different times to determine the best time to insert dental implants. METHODS: Ten consecutive patients with severe maxillary (two patients) or mandibular (eight patients) atrophy underwent surgical osteodistraction with an extraosseous distractor. Seven days after the surgery, the distractor was activated at a rate of 1 mm/day until achieving the planned bone lengthening. The distractor was removed after a consolidation period of 70 days. Bone biopsies were obtained at implant insertion: 70 days after the end of distraction on the day of distractor removal in six patients (group A) or 180 days afterwards in four patients (group B). The biopsies were evaluated histologically and histomorphometrically to measure the osteocyte lacunar area (OLA). RESULTS: The histologic and histomorphometrical analysis of the distracted bone 70 days after the end of distraction showed well-organized lamellar bone. At 180 days, the bone was more compact and mature; the mineralization of the matrix was greater; and an increased, but small, amount of marrow space was evident (35% versus 45%). The mean OLA was 80.11 +/- 27.59 microm2 in group A and 70.4 +/- 33.58 microm2 in group B. The difference between the two biopsy groups was not significant (P = 0.315). CONCLUSION: The results of this study showed that there was definitely similar bone formation in the distracted area for both healing periods, and placing implants clinically worked in both of these time periods in the limited number of cases observed.