Deep-learning algorithm to detect fibrosing interstitial lung disease on chest radiographs.

BACKGROUND: Antifibrotic therapies are available to treat chronic fibrosing interstitial lung diseases (CF-ILDs), including idiopathic pulmonary fibrosis. Early use of these treatments is recommended to slow deterioration of respiratory function and to prevent acute exacerbation. However, identifying patients in the early stages of CF-ILD using chest radiographs is challenging. In this study, we developed and tested a deep-learning algorithm to detect CF-ILD using chest radiograph images. METHOD: From the image archive of Sapporo Medical University Hospital, 653 chest radiographs from 263 patients with CF-ILDs and 506 from 506 patients without CF-ILD were identified; 921 were used for deep learning and 238 were used for algorithm testing. The algorithm was designed to output a numerical score ranging from 0 to 1, representing the probability of CF-ILD. Using the testing dataset, the algorithm's capability to identify CF-ILD was compared with that of doctors. A second dataset, in which CF-ILD was confirmed using computed tomography images, was used to further evaluate the algorithm's performance. RESULTS: The area under the receiver operating characteristic curve, which indicates the algorithm's detection capability, was 0.979. Using a score cut-off of 0.267, the sensitivity and specificity of detection were 0.896 and 1.000, respectively. These data showed that the algorithm's performance was noninferior to that of doctors, including pulmonologists and radiologists; performance was verified using the second dataset. CONCLUSIONS: We developed a deep-learning algorithm to detect CF-ILDs using chest radiograph images. The algorithm's detection capability was noninferior to that of doctors.

[Breast and Advanced Ovarian Double Cancer with a BRCA2 Pathogenic Variant-A Case Report].

A 49-year-old woman presented with abdominal pain. A computed tomography scan revealed a left breast mass with suspected peritoneal dissemination. She had no notable family history of the disease. Following a detailed examination, she was diagnosed with ovarian cancer(Stage ⅢC)and left breast cancer(Stage Ⅰ). After confirming the diagnosis of ovarian cancer with a laparoscopic biopsy, neoadjuvant chemotherapy was scheduled. Due to its efficiency in reducing tumor burden, debulking surgery was also performed. While receiving adjuvant chemotherapy for ovarian cancer, concomitant anastrozole was administered for breast cancer. A pathogenic variant of BRCA2 was subsequently identified. Once adjuvant chemotherapy for ovarian cancer had been completed, a left mastectomy and sentinel lymph node biopsy were performed as management for breast cancer. The patient will continue treatment with anastrozole for breast cancer and olaparib for ovarian cancer and will be followed up appropriately.

Comparison between robot-assisted thoracoscopic surgery and video-assisted thoracoscopic surgery for mediastinal and hilar lymph node dissection in lung cancer surgery.

OBJECTIVES: Lymph node dissection (LND) with robot-assisted thoracoscopic surgery (RATS) in lung cancer surgery has not been fully evaluated. The aim of this study was to compare LND surgical results between video-assisted thoracoscopic surgery (VATS) and RATS. METHODS: We retrospectively compared perioperative parameters, including the incidence of LND-associated complications (chylothorax, recurrent and/or phrenic nerve paralysis and bronchopleural fistula), lymph node (LN) counts and postoperative locoregional recurrence, among 390 patients with primary lung cancer who underwent lobectomy and mediastinal LND by RATS (n = 104) or VATS (n = 286) at our institution. RESULTS: The median total dissected LN numbers significantly differed between the RATS and the VATS groups (RATS: 18, VATS: 15; P < 0.001). They also significantly differed in right upper zone and hilar (#2R + #4R + #10L) (RATS: 12, VATS: 10; P = 0.002), left lower paratracheal and hilar (#4L + #10L) (RATS: 4, VATS: 3; P = 0.019), aortopulmonary zone (#5 + #6) (RATS: 3, VATS: 2; P = 0.001) and interlobar and lobar (#11 + #12) LNs (RATS: 7, VATS: 6; P = 0.041). The groups did not significantly differ in overall nodal upstaging (P = 0.64), total blood loss (P = 0.69) or incidence of LND-associated complications (P = 0.77). CONCLUSIONS: In this comparison, it was suggested that more LNs could be dissected using RATS than VATS, especially in bilateral superior mediastinum and hilar regions. Accumulation of more cases and longer observation periods are needed to verify whether RATS can provide the acceptable quality of LND and local control of lung cancer.

A rare case of combined thymoma and a multilocular thymic cyst discovered due to chest pain.

BACKGROUND: A thymoma with chest pain and multilocular thymic cysts (MTCs) is very rare. CASE PRESENTATION: A 49-year-old man presented to another hospital complaining of an anterior chest pain. Chest computed tomography (CT) showed an anterior mediastinal tumor 60 × 30 × 55 mm in size. The boundary with the pericardium or left brachiocephalic vein seemed to be partially unclear while enhanced by the contrast medium, and so the tumor could have invaded them. No definitive diagnosis of myasthenia gravis was made although the serum anti-acetylcholine receptor antibody count was high. We performed an extended thymectomy with combined partial resection of left brachiocephalic vein, left upper lobe, and left phrenic nerve. He was discharged with no chest pain and no complications post-surgery. The tumor was pathologically type B2 thymoma with hemorrhage necrosis and MTCs, and we diagnosed Masaoka stage II because of no histological infiltration to the organs. CONCLUSIONS: We speculated that hemorrhagic necrosis due to infarction in tumor caused the inflammation to spread to the surrounding organs, which was related to the chest pain and the development of MTCs.

Transformation from adenocarcinoma to squamous cell carcinoma associated with long-term administration of EGFR-TKIs.

Although patients with non-small cell lung cancer exhibiting EGFR mutations generally respond to tyrosine kinase inhibitors (TKIs), the majority of patients acquire resistance ~1 year after treatment. EGFR T790M mutations, MET or HER2 amplifications and phenotypic transformations contribute to the mechanism of EGFR-TKI resistance. The transformation of small cell lung cancer frequently occurs, although few convert to squamous cell carcinoma associated with the administration of EGFR-TKIs. The current study reports a case of EGFR-mutated adenocarcinoma of the lung that transitioned to squamous cell carcinoma in association with long-term EGFR-TKIs administration.

Comparison of medium-term survival outcomes between robot-assisted thoracoscopic surgery and video-assisted thoracoscopic surgery in treating primary lung cancer.

OBJECTIVES: Robot-assisted thoracoscopic surgery (RATS) for primary lung cancer has been spreading rapidly in Japan. While RATS has various technical advantages over video-assisted thoracoscopic surgery (VATS), the quality of surgery from an oncologic viewpoint must be maintained, and the evaluation of medium- to long-term survival outcomes is momentous. METHODS: This study included 299 patients with primary lung cancer (VATS, n = 246; RATS, n = 53) who underwent lobectomy and mediastinal lymph node dissection at our hospital. We reviewed and compared perioperative factors, the number of dissected lymph nodes, and postoperative recurrence between the VATS and RATS groups. We also compared the postoperative survival rates among 98 patients (49 patients in each group) whose background factors were adjusted by propensity score matching (PSM). RESULTS: After PSM, a significant difference was found in the total operative time between the two groups (p < 0.01); however, no difference was found between the RATS console time and VATS total operative time (p = 0.68). Postoperative recurrence was not significantly different between the groups (VATS, 14%; RATS, 6%; p = 0.18). The 3-year recurrence-free survival rate was not significantly different between the groups (VATS, 91.7%; RATS, 91.2%; p = 0.21). CONCLUSIONS: RATS had promising survival results, which were similar to those of VATS even after PSM. Further case series and longer observation periods are needed to determine what technical benefits of RATS may affect the prognosis of lung cancer.

Initial Results of Robotic Surgery for Primary Lung Cancer: Feasibility, Safety and Learning Curve.

BACKGROUND: At the end of 2016, robot-assisted thoracoscopic surgery (RATS) was still not covered by Japanese national health insurance. Therefore, few institutions in Japan perform RATS and even fewer have reported procedures as they occurred earlier. So, we decided to focus on the initial results of RATS for primary lung cancer. METHODS: We retrospectively reviewed 44 patients who underwent RATS for primary lung cancer from January 2011 to August 2016. After mastering the initial procedure, we introduced a completely portal robotic pulmonary resection procedure using a carbon dioxide insufflation system. Cases were divided into 2 groups: the early period (20 cases) and the later period (24 cases). RESULTS: There was no case of conversion to video-assisted thoracoscopic surgery or thoracotomy. In the 44 cases of primary lung cancer, median operating time was 239.5 min, console time was 179 min, blood loss was 10 mL, drainage period was 2 days, morbidity of Grade 2 or more (Clavien-Dindo classification) was 18.2%, morbidity of Grade 3 or more was only 4.6%, and there was no 30-day mortality. Median operating and console times were significantly shorter in the later period (215 min and 159.5 min, respectively) than in the initial period (300.5 min and 228 min, respectively). Median blood loss was significantly lower in the later period (5 mL) than in the initial period (50 mL). Five-year overall and disease-free survival rates were 100% and 88.9%, respectively. CONCLUSION: RATS for primary lung cancer is feasible and safe, has a faster learning curve, and provides satisfactory. Studies with longer follow-ups and larger numbers of cases are necessary.

Prognostic Significance of Solid and Micropapillary Components in Invasive Lung Adenocarcinomas Measuring ≤3 cm.

BACKGROUND/AIM: We aimed to analyze the clinical impact of solid and micropapillary components in a series of Japanese patients resected for ≤3 cm lung adenocarcinoma. PATIENTS AND METHODS: A total of 115 patients with ≤3 cm lung adenocarcinomas were reviewed and classified according to the American Thoracic Society and the European Respiratory Society classification. The presence of solid (S+) or micropapillary component (MP+) was defined when the component constituted ≥1% of the entire tumor. The impact of these components on disease-free (DFS) and disease-specific (DSS) survival was analyzed. RESULTS: Thirty (26.1%) cases with S+ and 27 (23.5%) with MP+ were identified, and multivariate analysis indicated that S+ status significantly reduced the duration of DFS and DSS. In 86 patients of acinar- and papillary-predominant subgroups, S+ and/or MP+ had the most significant effect on DFS and DSS by multivariate analysis. CONCLUSION: S+ and/or MP+ status predict worse prognosis in patients with acinar- and papillary-predominant lung adenocarcinoma.

Cytoplasmic expression of maspin predicts unfavourable prognosis in patients with squamous cell carcinoma of the lung.

AIMS: Maspin is known to be a tumour suppressor protein, and its prognostic significance in patients with several types of cancer, including lung squamous cell carcinoma (SCC), has been reported. However, its prognostic impact on lung SCC has been controversial. We explored the prognostic value of maspin expression with particular reference to its subcellular localization in patients with lung SCC. METHODS AND RESULTS: Paraffin-embedded tissue samples from 101 curatively resected patients with lung SCC were analysed immunohistochemically using an antibody for maspin. Maspin positivity was defined as strong expression in only the cytoplasm and observed in 25 patients (24.6%). It correlated significantly with the presence of lymph node metastasis (P = 0.006) and higher pathological stage (P = 0.003). The patients were followed-up for 2-119 months (median: 50 months), and the maspin-positive group had shorter disease-free survival (DFS) and disease-specific survival (DSS) by log-rank test (P = 0.002, P = 0.016, respectively). Multivariate analysis revealed that the status of maspin was the only independent prognostic factor for DFS and DSS (P = 0.017, P = 0.047, respectively). CONCLUSIONS: Cytoplasmic expression of maspin could be an independent unfavourable prognostic indicator in patients with lung SCC.

Microcalcification of Tumor is a Predictor of Response to Neoadjuvant Chemotherapy for Invasive Breast Carcinoma.

BACKGROUND: In recent years, neoadjuvant chemotherapy (NAC) is often performed for patients with unresectable breast carcinoma or without indication of breast conserving therapy. However, it is currently difficult to predict response to NAC with diagnostic imaging of breast carcinoma. In this study, we investigated imaging findings that could serve as a predictor of the response to NAC for patients with invasive breast carcinoma. METHODS: Twenty-six patients with invasive breast carcinoma who received NAC at the Division of Breast and Endocrine Surgery of Tottori University Hospital between January 2010 and May 2014 were retrospectively investigated. Their imaging findings from mammograms and ultrasonograms were reviewed. The association between findings on mammograms and ultrasonograms captured before NAC and response to treatment after NAC was examined. RESULTS: Of the 26 patients with invasive breast carcinoma, 19 (73%) responded well to treatment and 7 (27%) did not. Most notably, all 10 patients who had microcalcifications on mammogram responded well to treatment (53% of responders), and all patients who did not respond to treatment had no microcalcifications (P < 0.05). Of these 10 patients, 9 (90%) had microcalcifications of comedo type and one (10%) had non comedo type. As a distribution, 8 of the 10 (80%) had a clustered type of microcalcifications and the remaining 2 (20%) had a segmental type of them. CONCLUSION: Microcalcifications of tumor observed in mammogram (particularly comedo type) could be a predictor of response to NAC for patients with invasive breast carcinoma.

Cytoplasmic maspin expression is a predictor of poor prognosis in patients with lung adenocarcinoma measuring <3 cm.

AIMS: Maspin is known to be a tumour suppressor protein, and few studies focused upon its prognostic significance in patients with small-size lung adenocarcinoma have been reported; however, its clinical significance remains controversial. We explored the prognostic value of maspin with particular reference to its subcellular localization in patients with resected lung adenocarcinoma measuring <3 cm. METHODS AND RESULTS: Immunohistochemical analyses were performed on resected 110 specimens of lung adenocarcinoma measuring <3 cm. Maspin positivity was defined as strong expression in only the cytoplasm and was observed in 27 patients (24.5%). It correlated significantly with the presence of lymph node metastasis (P = 0.009) and micropapillary component (P < 0.001). The patients were followed-up for 6-88 months (median: 71 months), and the maspin-positive group had shorter disease-free survival (DFS) and overall survival (OS) by log-rank test (P < 0.001, P < 0.001, respectively). Using Cox's multivariate analysis, the status of maspin was an independent prognostic factor for DFS and OS (P = 0.004, P = 0.022, respectively), as well as lymph node metastasis. CONCLUSIONS: Cytoplasmic maspin expression could be an independent poor prognostic indicator of patients with lung adenocarcinoma measuring <3 cm.

TGF-ß in dentin matrix extract induces osteoclastogenesis in vitro.

Previously, we have demonstrated that the extracellular matrix from dentin affects osteoclastic activity in co-culture between osteoclast and osteoblast-rich fraction from mouse marrow cells. In the present study, we aimed to investigate the mechanisms of dentin matrix extract-induced osteoclastogenesis in mouse bone marrow macrophages (BMMs). Dentin proteins were extracted from bovine incisor root dentin using 0.6 M HCl. BMMs were cultured in α-MEM containing macrophage colony-stimulating factor/receptor activator of nuclear factor kappa-B ligand in the presence or absence of dentin matrix extract. Tartrate-resistant acid phosphatase (TRAP)-positive cell number, total TRAP activity, and the mRNA levels of osteoclast-related genes, assayed by real-time RT-PCR, were determined as markers of osteoclastogenesis. A neutralizing antibody against transforming growth factor-ß1 (TGF-ß1), SB431542, a TGF-ß receptor inhibitor, and ELISA were used to determine the role of TGF-ß1. We observed increases in TRAP-positive cell number, TRAP activity, and the mRNA levels of osteoclast-related genes of BMMs cultured with dentin extract. The use of a neutralizing antibody against TGF-ß1 or SB431542 inhibited the inductive effect of dentin extract, suggesting TGF-ß1 involvement. The addition of exogenous TGF-ß1, but not bone morphogenic protein-2, also increased osteoclastogenesis, corresponding to the ELISA determination of TGF-ß1 in the dentin extract. In conclusion, our results indicate that proteins from dentin matrix have an inductive effect in osteoclastogenesis, which is mediated, in part, by TGF-ß1.

Cytoplasmic maspin expression predicts poor prognosis of patients with soft tissue sarcomas.

BACKGROUND: Maspin is a 42 kDa protein known to act as a tumor suppressor. Although its function has not been fully elucidated, numerous reports have investigated the prognostic impact of maspin in patients with several types of cancer. However, there have been no reports on the association between maspin expression and the prognosis of patients with soft tissue sarcomas (STS). The aim of this study was thus to explore the association of maspin expression with the prognosis of patients with STS. METHODS: One-hundred and eight paraffin-embedded STS tissue samples were immunohistochemically analyzed using antibodies for maspin and Ki-67 antigen. The patients were followed up for 1 to 300 months (median: 33 months) and the prognostic value was evaluated by log-rank test and Cox's regression hazard model. RESULTS: Cytoplasmic maspin expression was observed in 48.1% of specimens, and was significantly correlated with a higher FNCLCC grade (P = 0.002) and the presence of distant metastases (P = 0.001), and those with cytoplasmic maspin expression had both shorter disease-free survival (DFS) and overall survival (OS) by log-rank test (P <0.001, P = 0.001, respectively). By Cox's multivariate analysis, the presence of distant metastases was the only prognostic factor for DFS and OS. CONCLUSIONS: This is the first report to reveal an association between maspin expression and the prognosis of patients with STS. Although further studies with a larger series of patients and a longer follow-up period will be needed, cytoplasmic maspin expression could be an indicator of unfavorable prognosis in patients with STS. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_205.

Characterization of pulp and follicle stem cells from impacted supernumerary maxillary incisors.

PURPOSE: The purpose of this study was to characterize dental pulp and dental follicle stem/progenitor cells (DPSCs and DFSCs) from the same impacted supernumerary maxillary incisors (ISMIs). METHODS: DPSCs and DFSCs were obtained from ISMIs of healthy children (six to 12 years old) by the outgrowth culture method and were compared for proliferation, colony-forming capacity, gene expression, cell surface markers, and trilineage differentiation capacity. RESULTS: The volume of follicle tissue obtained was much larger than that for pulp tissue. DPSCs and DFSCs showed fibroblast-like morphology, expressed the stem cell-associated genes, OCT4 and NANOG, and were positive for CD146, CD90, and CD105 but negative for CD45. The cell proliferation rate and colony-forming capacity of DFSCs were significantly higher than those for DPSCs. Under inductive culture conditions, DPSCs and DFSCs differentiated into osteogenic, adipogenic, and chondrogenic lineage cells. CONCLUSIONS: These results demonstrated that dental pulp and dental follicle stem/progenitor cells have similar mesenchymal stem cell characteristics, but DFSCs are easily accessible for cell culture and have a higher proliferation capacity than DPSCs. It also appears that dental follicle stem/progenitor cells might have some advantages as a stem cell resource for regenerative medicine.

Excellent prognosis of lepidic-predominant lung adenocarcinoma: low incidence of lymphatic vessel invasion as a key factor.

AIM: To clarify the prognostic value of predominant histological subtypes for small-sized lung adenocarcinoma. MATERIALS AND METHODS: Sixty-four specimens of resected invasive lung adenocarcinoma less than 20 mm in diameter with no lymph node metastasis were studied. These specimens were microscopically classified into predominant histological subtypes (21 lepidic, 16 acinar, 24 papillary, and three solid) according to the International association for the study of lung cancer/American thoracic society/European respiratory society adenocarcinoma classification. The relationships between tumor relapse and predominant histological subtypes were statistically analyzed. In addition the relationships between several pathological factors and predominant histological subtypes were statistically assessed. RESULTS: Kaplan-Meier relapse-free curves showed a five-year relapse-free rate of 100% in 64 patients with lepidic-predominant adenocarcinoma, compared with a rate of 73.7% (p=0.035 by log rank test) in patients with non-lepidic-predominant adenocarcinoma (papillary, acinar, and solid). The only statistically significant pathological factor between lepidic-predominant and non-lepidic-predominant histological subtypes was lymphatic vessel invasion as assessed by logistic regression analysis. CONCLUSION: In small-sized lung adenocarcinoma, lepidic-predominant histological subtype is the best prognostic factor, and a low incidence of lymphatic vessel invasion in the histological subtype is a key factor for an excellent prognosis.

Desmoid tumor requiring differentiation from port-site relapse after surgery for lung cancer.

Thoracoscopic left lower lobectomy with lymph node dissection for lung cancer was performed in a 76-year-old man. The diagnosis was pT2aN2M0 adenocarcinoma. Sixteen months after surgery, CT revealed a pleural tumor measuring 38 mm at the surgical port wound. CT-guided biopsy revealed fibroma. However, the tumor size increased 4 months after biopsy, and surgery was performed. An intraoperative diagnosis revealed benign fibroma. Thoracoscopic tumorectomy was conducted. The pathological diagnosis was desmoid tumor. As the margins of the resected specimen were positive, radiotherapy was performed. During the 16-month follow-up period, there has been no relapse. Pleural desmoid tumors must be differentiated from port-site relapse.

Detection of occlusal caries in primary teeth using swept source optical coherence tomography.

This study aimed to investigate swept source optical coherence tomography (SS-OCT) as a detecting tool for occlusal caries in primary teeth. At the in vitro part of the study, 38 investigation sites of occlusal fissures (noncavitated and cavitated) were selected from 26 extracted primary teeth and inspected visually using conventional dental equipment by six examiners without any magnification. SS-OCT cross-sectional images at 1330-nm center wavelength were acquired on the same locations. The teeth were then sectioned at the investigation site and directly viewed under a confocal laser scanning microscope (CLSM) by two experienced examiners. The presence and extent of caries were scored in each observation. The results obtained from SS-OCT and conventional visual inspections were compared with those of CLSM. Consequently, SS-OCT could successfully detect both cavitated and noncavitated lesions. The magnitude of sensitivity for SS-OCT was higher than those for visual inspection (sensitivity of visual inspection and SS-OCT, 0.70 versus 0.93 for enamel demineralization, 0.49 versus 0.89 for enamel cavitated caries, and 0.36 versus 0.75 for dentin caries). Additionally, occlusal caries of a few clinical cases were observed using SS-OCT in vivo. The results indicate that SS-OCT has a great detecting potential for occlusal caries in primary teeth.

Thymic metastasis of breast cancer 22 years after surgery: a case report.

We report a rare case of thymic metastasis of breast cancer. A 68-year-old woman, who had undergone surgery for cancer in her right breast and had been free of recurrence for 22 years, was noted to have an abnormal shadow on a chest X-ray at a regular medical checkup. Further workup, including chest CT, revealed a 22 × 18-mm mass in the anterior mediastinum. Fluorine-18-fluorodeoxyglucose-PET showed increased fluorine-18-fluorodeoxyglucose uptake that was highly suggestive of thymoma. Thoracoscopic thymothymectomy was performed. The tumor had invaded the pericardium, which was also resected. A small nodule was found in the right lung, and it was also resected. The intraoperative frozen-section diagnosis was breast cancer metastasis to the thymus and lung. The pathological diagnosis was luminal A solid tubular carcinoma (strongly estrogen receptor and progesterone receptor positive, HER2 negative) with an MIB-1 index of less than 5%. After surgery, the patient was treated with an aromatase inhibitor. As of August 2013, she has been free of recurrence for more than 36 months. It is extremely rare for breast cancer to metastasize to the thymus more than 20 years after surgery.

Efficacy of platelet-rich plasma gel and hyaluronan hydrogel as carriers of electrically polarized hydroxyapatite microgranules for accelerating bone formation.

The technology for electrical polarization and characterization of hydroxyapatite (HA) microgranules has been developed. This study aimed to examine and compare the efficacy of composites comprising electrically polarized HA (pHA) microgranules and platelet-rich plasma (PRP) or hyaluronan (HAN) in osteoconductivity. Composites of HA microgranules with or without electrical polarization and either PRP or HAN (PRP+pHA, PRP+HA, HAN+pHA, and HAN+HA, respectively), as well as pHA and HA microgranules were implanted randomly into holes created in the medial femoral condyle or tibial tuberosity of rabbits. As a control, PRP or HAN gel alone was implanted, or the bone holes were left empty. Each group included six animals. After 6 weeks, histological examination was performed, and osteoclastic and osteoblastic cell activities were assessed by cell counting. Although PRP alone could not induce bone formation, PRP+pHA and PRP+HA composites, especially the former, activated osteogenic cells and enhanced bone formation. This effect was not prominent in the HAN+pHA and HAN+HA composites. PRP+HA composites formed a gel in which the ceramic particles were dispersed and entrapped in the fibrin network of PRP. It is assumed that these particles provide scaffolds for osteogenic cells, and when electrically polarized, can activate the cells in co-operation with the positive effects of the PRP, resulting in enhanced bone formation. Conversely, it is conceivable that this composite gel cannot act as an accelerator for woven bone formation, because HAN with low viscoelasticity is absorbed rapidly after implantation, the hydrated network containing HA microgranules is destroyed, and the HA microgranules effuse with HAN from the bone hole.

Acceleration of new bone formation by an electrically polarized hydroxyapatite microgranule/platelet-rich plasma composite.

We have developed a technology for the electrical polarization and electrical characterization of hydroxyapatite (HA) microgranules. In order to improve handling of ceramic powders to fulfill complex geometrical demands, platelet-rich plasma (PRP) containing many growth factors was chosen as a carrier of HA microgranules. In this study, the effects of this electrically polarized HA microgranule/PRP composite on new bone formation were examined. To compare osteoconductivity, HA microgranules with or without electrical polarization/PRP composite gel, HA microgranules alone with or without electrical polarization, or PRP gel were implanted into holes in the medial femoral condyles of rabbits. As a control, some of the bone holes were left empty (n=6 in each group). Histological examination was performed 3 and 6 weeks after the surgical operation. It was suggested that PRP alone could not induce new bone formation until 6 weeks after implantation. HA microgranules with or without electrical polarization/PRP composite, especially the former, activated osteogenic cells, resulting in enhanced bone formation. It was confirmed that electrical polarization treatment of HA microgranules can accelerate new bone formation, and that this effect is enhanced by forming a complex within the PRP.