Primary stability of different implant macrodesigns in a sinus floor elevation simulated model: an ex vivo study.

BACKGROUND: A novel type of implant (Straumann® BLX implant) has been developed for certain stability from the mechanical and biological aspects and is expected for the implant placement in atrophic maxilla with sinus floor elevation (SFE). PURPOSE: The aim of this study was to evaluate the primary stability in the implants with different macrodesigns in an SFE simulated model. Primary stabilities defined as maximum insertion torque (MIT) and implant stability quotient (ISQ) were compared between this novel type of implant and other types. MATERIALS AND METHODS: Five types of Straumann® 10 mm length implants (Standard Plus; SP, Tapered Effect; TE, Bone Level; BL, Bone Level Tapered; BLT and BLX) and two types of Straumann® 6 mm length implants (SP short, BLX short) were used in this study. Each implant was inserted through 5 mm-thick porcine iliac crest blocks (an SFE simulated model). Primary stability was evaluated by using MIT and ISQ. RESULTS: The mean value of MIT for BLX group showed significantly higher values than SP, BL (p < 0.01), and TE (p < 0.05) groups. The mean value of ISQ for BLX group was significantly higher than the other groups (p < 0.01). The mean value of MIT and ISQ for BLX and BLX short group were significantly higher than those for SP and SP short group (p < 0.01). CONCLUSIONS: In an SFE simulated ex vivo model, BLX group showed the highest values. These results suggest that implant selection can play a crucial role in the achievement of primary stability during SFE and simultaneous implant placement.

A stepwise under-prepared osteotomy technique improves primary stability in shallow-placed implants: a preliminary study for simultaneous vertical ridge augmentation.

Simultaneous vertical ridge augmentation (VRA) can reduce treatment procedures and surgery time, but the concomitant reduction in primary stability (PS) of a shallow-placed implant imparts risk to its prognosis. Although several studies have reported improvements in PS, there is little information from any simultaneous VRA model. This study aimed to evaluate whether tapered implants with stepwise under-prepared osteotomy could improve the PS of shallow-placed implants in an in vitro model of simultaneous VRA. Tapered implants (Straumann® Bone Level Tapered implant; BLT) and hybrid implants (Straumann® Bone Level implant; BL) were investigated in this study. A total of 80 osteotomies of different depths (4, 6, 8, 10 mm) were created in rigid polyurethane foam blocks, and each BLT and BL was inserted by either standard (BLT-S, BL-S) or a stepwise under-prepared (BLT-U, BL-U) osteotomy protocol. The PS was evaluated by measuring maximum insertion torque (IT), implant stability quotient (ISQ), and removal torque (RT). The significance level was set at P < 0.05. There were no significant differences in IT, ISQ or RT when comparing BLT-S and BL-S or BLT-U and BL-U at placement depths of 6 and 8 mm. When comparison was made between osteotomy protocols, IT was significantly greater in BLT-U than in BLT-S at all placement depths. A stepwise under-prepared osteotomy protocol improves initial stability of a tapered implant even in a shallow-placed implant model. BLT-U could be a useful protocol for simultaneous VRA.

Additional Effects of Platelet-Rich Fibrin on Bone Regeneration in Sinus Augmentation With Deproteinized Bovine Bone Mineral: Preliminary Results.

PURPOSE: Platelet-rich fibrin (PRF) has been reported to contribute to bone regeneration; however, little is known about details with deproteinized bovine bone mineral (DBBM). This study aims to evaluate additional effects of PRF on bone regeneration in sinus augmentation with DBBM. MATERIALS AND METHODS: Sinus augmentations were made with DBBM/PRF mixture as lateral approach for 4 sinuses from 4 patients. Bone biopsies were obtained from posterior maxilla at the implant placements 7 or 10 months after sinus augmentations. Histological observations and histomorphometric analyses from augmented areas were performed. RESULTS: The new bone formation was found around the DBBMs with very good contact while surfaces of DBBMs were partly resorbed. Osteoclasts recognized the DBBMs for remodeling, followed by new bone running. The histomorphometric analyses revealed that mean percentages of newly formed bone were 31.7 ± 1.2%, 21.0 ± 1.0%, 38.0 ± 0.6%, and 47.0 ± 0.6%, respectively (mean 34.5 ± 5.7%). CONCLUSIONS: Additional effects of PRF could be found because of higher percentages of newly bone formation by DBBM/PRF mixture than those by DBBM individual in previous reports.

Apoptotic function of tumor-associated antigen RCAS1 in oral squamous cell carcinoma.

BACKGROUND: Receptor-binding cancer antigen expressed on SiSo cell (RCAS1) is derived from uterine adenocarcinoma and can induce apoptosis in lymphocytes, allowing tumor cells to escape from immune surveillance. RCAS1 is reportedly expressed in a membranous pattern on tumor cell or soluble one in serum of patients. The aim of this study was to investigate expression patterns of RCAS1 and the effect on apoptosis in oral squamous cell carcinoma (OSCC) cell lines. METHODS: In four kinds of OSCC cell lines (HSC-2, HSC-3, SQUU-A, and SQUU-B), RCAS1 mRNAs and proteins were determined by RT-PCR and immunocytochemistry. Membranous RCAS1 was determined by flow cytometry. Culture supernatants were analyzed for detection of soluble RCAS1 by dot blotting and enzyme-linked immunosorbent assay. Apoptotic ability of RCAS1 on the erythroid leukemia cell line K562 with the putative receptor was evaluated by flow cytometry in co-culture with highly metastatic SQUU-B, with knocked-down RCAS1 cells or in a no-cell contact condition. RESULTS: RCAS1 mRNA and proteins were expressed in all of OSCC cell lines. Membranous pattern were expressed in all cell lines, while soluble pattern was detected in all supernatants. RCAS1 mRNA, membranous and soluble RCAS1 were significantly seen in SQUU-B more than the other 3 cell lines (P < 0.05). K562 apoptosis was induced in co-culture with each of all cell lines, particularly with SQUU-B. Apoptosis was markedly reduced in co-culture with RCAS1 knockdown cells, but was induced in co-culture without cell contract of SQUU-B. CONCLUSIONS: Our study suggests that RCAS1 has an apoptotic function via membranous/soluble expression pattern in OSCC cells. RCAS1 may thus affect tumor escape from immune surveillance in OSCC by inducing apoptosis.

Appropriate duration of driving restrictions after inappropriate therapy from implantable cardiac shock devices-interim analysis of the Nippon Storm Study.

BACKGROUND: Little is known regarding the appropriate duration for driving restrictions after inappropriate implantable cardiac shock device (ICSD) therapy. METHODS AND RESULTS: We evaluated the Nippon Storm Study data, and found that inappropriate ICSD therapy occurred in 114 (7.6%) patients during a median follow-up of 464 days. Among those patients, 25 experienced further inappropriate ICSD therapy during a subsequent median follow-up of 380 days. Time-dependent recurrence of inappropriate ICSD therapy occurred in 19 (76%) patients within 180 days. CONCLUSIONS: The interval for driving restrictions after inappropriate ICSD therapy can be reduced.

Immunohistochemical location of the p75 neurotrophin receptor (p75NTR) in oral leukoplakia and oral squamous cell carcinoma.

BACKGROUND: Recent studies have demonstrated that the p75 neurotrophin receptor (p75NTR) is a useful marker of keratinocyte stem cells. Although the stem cell markers of original normal tissue have been used to identify cancer stem cells in a variety of cancers, the expression and function of p75NTR have been poorly understood in oral squamous cell carcinoma (OSCC). The objective of this study is, thus, to examine p75NTR expression immunohistochemically in oral leukoplakia (OL), the most frequent precancerous lesion, and OSCC, and to reveal the usefulness of p75NTR as a marker for undifferentiated cancer cells and a novel prognostic factor for OSCC patients. METHODS: In this study immunohistochemical expression of p75NTR, Ki-67, cytokeratin (CK) 5, and CK14 was examined in 112 cases of OL and 81 of OSCC. The labeling indices (LIs) of p75NTR and Ki-67 were calculated, and the association of these LIs with histopathologic characteristics was then evaluated. RESULTS: In the normal oral epithelium and OL, p75NTR was expressed only in the basal layer, and its LI was invariant, irrespective of the extent of epithelial dysplasia. In OSCC, however, p75NTR-LI was significantly increased in association with upgrading of histologic grade and mode of tumor invasion. Furthermore, the prognosis of the high p75NTR-LI group (LI ≥ 53.1%) was poorer than that of the low p75NTR-LI group (LI < 53.1%). CONCLUSIONS: These results suggest that p75NTR is expressed in undifferentiated cell populations in OL and OSCC. Furthermore, p75NTR is possibly involved in invasion and poor prognosis in OSCC.

Single nucleotide polymorphisms of the vascular endothelial growth factor gene associated with incidence of oral squamous cell carcinoma.

BACKGROUND: Vascular endothelial growth factor (VEGF) plays an important role in promoting angiogenesis and is overexpressed in several malignancies. Polymorphisms of the VEGF gene can alter VEGF protein expression, which may be biologically significant and account for heterogeneity in disease risk and outcome. The aim of this case-control study was to evaluate potential associations between single nucleotide polymorphisms (SNP) of the VEGF gene with susceptibility of oral squamous cell carcinoma (OSCC). PATIENTS AND METHODS: Five VEGF SNP (-1154 G/A, +405 G/C, +936 C/T, -2578 C/A and -460 C/T) were determined in peripheral blood isolated from 80 patients with OSCC and from 40 age- and gender-matched healthy volunteers (RT-PCR). RESULTS: The +936 T allele and the -2578 C/A SNP were expressed significantly more often in the OSCC-group (P=0.002; P<0.0001) where three associations between two SNPs (+936 and +405, -2578 and -1154, -460 and -2578) were found. CONCLUSION: Our findings provide support that +936 T allele and -2578 C/A SNP of the VEGF gene alone or in combination with other SNP are associated with OSCC. The SNPs may be used as biomarker for the development of specialized anti-VEGF drugs. Further studies must confirm the value of preoperative genetic analysis for prognosis.

Long-term response of osteogenic cells on micron and submicron-scale-structured hydrophilic titanium surfaces: sequence of cell proliferation and cell differentiation.

OBJECTIVE: Modifications of surface topography and surface chemistry are key factors for guiding target cells during dental implant healing. Recent in vitro studies confirmed promotion of early osteogenic cell differentiation on submicron scaled surfaces in particular when hydrophilized. However, no long-term observations on both osteogenic cell proliferation as well as on cell maturation have been reported for respectively modified surfaces. Aim of this study was to monitor osteogenic cell proliferation and expression of specific osteogenic cell differentiation markers on a protein level over an extended period of 3 weeks with respect to surface modifications. MATERIAL AND METHODS: Modified titanium (Ti) disks were obtained from Institute Straumann, representing the following surfaces: smooth pretreatment (PT), sandblasted/acid etched (SLA), and hydrophilized (modSLA). Surface topography was analyzed by scanning electron microscopy, surface elemental composition was assessed by X-Ray Photoelectronic Spectroscopy (XPS). Tissue culture polystyrene (TCPS) served as a control substrate. Human osteogenic cells (HOB-c) were cultivated on the respective substrates. After 24 hrs, 48 hrs, 72 hrs, 7 d, 14 d and 21 d, cell count was assessed as well as osteogenic cell differentiation utilizing cellular Quantitative Immuno-Cytochemistry (QIC) assay for collagen type I (COL), alkaline phosphatase (AP), osteopontin (OPN) and osteocalcin (OC). Data were normalized with respect to internal controls. RESULTS: In contrast to the other modified Ti disks, modSLA stands out due to low surface carbon contamination. TCPS and PT surfaces preserved a rather immature, mitotic active osteogenic phenotype (high proliferation rates, no increase of OC production), SLA and especially modSLA surfaces promoted the maturation of osteogenic precursors into post-mitotic osteoblasts. In detail, modSLA resulted in lowest cell proliferation rates, but exhibited highest expression rates of OC. DISCUSSION: Our results, which confirm previous studies, reveal long-term promotion of osteogenic cell maturation by topography (micron and submicron scale roughness) and surface hydrophilicity.

Hematogenous cytokeratin 20 mRNA detection has prognostic impact in oral squamous cell carcinoma: preliminary results.

BACKGROUND: The study was designed to detect disseminated tumor cells (DTCs) in postoperative peripheral blood of patients with oral squamous cell carcinoma (OSCC) and to determine their relevance as prognostic markers by cytokeratin (CK) expression analysis. MATERIALS AND METHODS: Forty samples of peripheral blood mononuclear cells (PBMCs) isolated 4 weeks after surgery were screened for occurrence of four CK mRNA transcripts by real-time quantitative RT qPCR. Detection of mRNA expression was compared with clinicopathological parameters and disease-free survival (DFS). RESULTS: CK 17 and CK 19 could not be detected in any samples. CK 18 and CK 20 were detectable in 1 (2.5%) and in 14 (35.0%), respectively. The detection of CK 20 was not significantly associated with lymph node status, clinical stage, or differentiation grade, but was significantly higher in patients with T3 and T4 OSCC (p = 0.04). DFS was not associated with tumor size, clinical stage, or differentiation grade. But poor DFS was significantly associated with the occurrence of lymph node metastasis (p = 0.01) and detection of CK 20 (p = 0.01). CONCLUSION: DTCs in PBMCs of postoperative patients with OSCC could only be detected by determination of CK 20 mRNA. Detection of CK 20 mRNA in peripheral blood seems to be of relevance for prognosis in OSCC.

Cytokeratin 17 mRNA expression has potential for diagnostic marker of oral squamous cell carcinoma.

PURPOSE: Determination of marker for identification of oral squamous cell carcinoma (OSCC) is important for early diagnosis and individual therapy. Cytokeratins (CKs) like CK 19 and CK 20 are known to be useful diagnostic and prognostic markers for solid tumors. The aim of this study was to evaluate the relevance of further CKs for diagnosis of OSCC. MATERIALS: In 10 OSCC and 5 normal mucosal samples, the expression patterns of 31 CK genes were examined by cDNA microarray in order to identify CKs with most pronounced over-expression. The results were verified for CK 17, CK 19, and CK 20 in addition to 46 OSCC samples by relative quantification (RQ) using SYBR green real-time reverse transcriptase polymerase chain reaction (RT qPCR). A correlation of the CK expressions with the tumor classification was carried out. RESULTS: cDNA microarray analyses showed that out of all CKs, CK 17 was up-regulated strongest in OSCC compared to normal samples, and over-expression was most significantly associated with diagnosis (P = 0.002). Expression rates of CK 19 and CK 20 were not significantly different between OSCC samples and normal samples. In 56 samples analyzed by real-time RT qPCR, CK 17 was over-expressed in 53 (94.6%), CK 19 in 18 (32.1%), and CK 20 in 7 (12.5%). The over-expression of CK 17 was significantly associated with metastases of neck lymph nodes (P < 0.05). CK 19 was significantly over-expressed in T3 and T4 OSCC, in stage III and IV patients (P < 0.05), and in poorly differentiated OSCC (P < 0.03). The over-expression of CK 20 was significantly associated with metastases of neck lymph nodes (P < 0.03). Determined by RQ, the mean value of CK 17 over-expression was significantly higher than that of the other CKs (P < 0.01), and was significantly associated with T1 and T2 OSCC (P < 0.03) and with stage I and II patients (P < 0.01). CONCLUSION: CK 19 might be linked to the clinical progression and differentiation of OSCC, and CK 20 could be associated with metastases of neck lymph nodes in OSCC. Due to the significant up-regulation and the strong over-expression, CK 17 might be the most suitable marker for diagnosis of OSCC out of the CK-family.

Significant impact of electrical storm on mortality in patients with structural heart disease and an implantable cardiac defibrillator.

BACKGROUND: Electrical storm (E-Storm), defined as multiple episodes of ventricular arrhythmias within a short period of time, is an important clinical problem in patients with an implantable cardiac defibrillator (ICD) including cardiac resynchronization therapy devices capable of defibrillation. The detailed clinical aspects of E-Storm in large populations especially for non-ischemic dilated cardiomyopathy (DCM), however, remain unclear. OBJECTIVE: This study was performed to elucidate the detailed clinical aspects of E-Storm, such as its predictors and prevalence among patients with structural heart disease including DCM. METHODS: We analyzed the data of the Nippon Storm Study, which was a prospective observational study involving 1570 patients enrolled from 48 ICD centers. For the purpose of this study, we evaluated 1274 patients with structural heart disease, including 482 (38%) patients with ischemic heart disease (IHD) and 342 (27%) patients with DCM. RESULTS: During a median follow-up of 28months (interquartile range: 23 to 33months), E-Storm occurred in 84 (6.6%) patients. The incidence of E-Storm was not significantly different between patients with IHD and patients with DCM (log-rank p=0.52). Proportional hazard regression analyses showed that ICD implantation for secondary prevention of sudden cardiac death (p=0.0001) and QRS width (p=0.015) were the independent risk factors for E-storm. In a comparison between patients with and without E-Storm, survival curves after adjustment for clinical characteristics showed a significant difference in mortality. CONCLUSION: E-Storm was associated with subsequent mortality in patients with structural heart disease including DCM.

Preoperative chronic sinusitis as significant cause of postoperative infection and implant loss after sinus augmentation from a lateral approach.

OBJECTIVES: Among intra/postoperative complications of sinus augmentation from a lateral approach, postoperative infection and implant loss are particularly important because they have irreversible consequences. The purpose of this study was to determine the causes of postoperative infection and implant loss after a lateral approach and to determine the appropriate prophylaxis and therapy. MATERIALS AND METHODS: In total, 109 patients (121 sinuses, 252 implants) were included in this study. The correlation between postoperative infection and implant loss and clinical variables was assessed using logistic regression analyses. RESULTS: Postoperative infection and implant loss occurred in 8/121 sinuses (6.6%). Infection had the strongest correlation to preoperative chronic sinusitis (p = 0.007), followed by timing of implant insertion. Implant loss had the strongest correlation to preoperative chronic sinusitis (p = 0.007), followed by sex, diabetes, postoperative use of dentures, and intraoperative perforation of the sinus membrane. CONCLUSIONS: Preoperative chronic sinusitis could be a significant cause of postoperative infection and implant loss when using sinus augmentation from a lateral approach. For appropriate prophylaxis and therapy, it is necessary to diagnose the presence of chronic sinusitis that should be treated with proper methods prior to sinus augmentation.

Cytokeratin 17 mRNA as a prognostic marker of oral squamous cell carcinoma.

Despite diagnostic and therapeutic advances, the 5-year survival rate of oral squamous cell carcinoma (OSCC) remains between 70-80% due to recurrences and secondary metastases to cervical lymph nodes. It is difficult to find these recurrences and metastases postoperatively, thus, careful follow-up is recommended. Cytokeratins (CKs) are intermediate filaments of the cytoskeleton and candidate prognostic biomarkers for OSCC, as they are overexpressed in OSCC compared with normal mucosa. The aim of the present study was to determine the relative levels of occurrence of 3 CK mRNA (CK17, CK19, CK20) transcripts in peripheral blood mononuclear cells (PBMC) using reverse transcription-quantitative polymerase chain reaction. The study comprised pre- and post-operative PBMC samples from 19 OSCC patients. In the good-prognosis group, 10 of 13 patients demonstrated reduced CK17 mRNA expression post-operatively, compared with pre-operative samples, conversely, only 3 of 6 patients in the poor-prognosis group had reduced post-operative CK17 mRNA expression. This difference was statistically significant (P<0.01). The disease-free survival rate of the group with reduced post-operative CK17 mRNA expression was significantly increased compared with the elevated CK17 mRNA group (P<0.01); however, the overall survival rates of the two groups were not significantly different. Neither CK19 mRNA nor CK20 mRNA were significantly expressed in the PBMC of OSCC patients. Overall, CK17 mRNA expression may be a useful prognostic biomarker for OSCC.

Clinicopathological evaluation of pre-operative chemoradiotherapy with S-1 as a treatment for locally advanced oral squamous cell carcinoma.

The administration of pre-operative chemotherapy with S-1 and concurrent radiotherapy at a total dose of 30 Gy was clinicopathologically evaluated as a treatment for locally advanced oral squamous cell carcinoma (OSCC) in the present study. The participants comprised 81 patients with OSCC, consisting of 29 patients with stage II disease, 12 patients with stage III disease and 40 patients with stage IV disease. All patients received a total radiation dose of 30 Gy in daily fractions of 2 Gy, 5 times a week, for 3 weeks, and the patients were concurrently administered S-1 at a dose of 80-120 mg, twice daily, over 4 consecutive weeks. Radical surgery was performed in all cases at 2-6 weeks subsequent to the end of pre-operative chemoradiotherapy. The most common adverse event was oropharyngeal mucositis, but this was transient in all patients. No severe hematological or non-hematological toxicities were observed. The clinical and histopathological response rates were 70.4 and 75.3%, respectively. Post-operatively, local failure developed in 6 patients (7.4%) and neck failure developed in 2 patients (2.5%). Distant metastases were found in 7 patients (8.6%). The overall survival rate, disease-specific survival rate and locoregional control rate at 5 years were 87.7, 89.9 and 90.6%, respectively. Locoregional recurrence occurred more frequently in patients that demonstrated a poor histopathological response compared with patients that demonstrated a good response (P<0.01). These results indicate that pre-operative S-1 chemotherapy with radiotherapy at a total dose of 30 Gy is feasible and effective for patients with locally advanced OSCC, and that little or no histopathological response may be a risk factor for locoregional recurrence in this treatment.

Investigation of optimal position for implantable loop recorders by potential mapping with Reveal DX.

BACKGROUND: Electrode positioning is important for the operation of implantable loop recorders (ILRs). This study aimed to investigate optimal electrode positions for the implantation of ILRs. METHODS: Fifteen male subjects participated in the study and R wave amplitude data were collected from 15 areas in the left anterior chest area, with 4 variations of electrode angles and body positions. RESULTS: The estimated minimum R wave amplitude values were greater than 0.3 mV (manufacturer-recommended value) when electrodes were angled vertically and positioned on the midclavicular line of the third and the forth intercostal spaces or on the left sternal border of the fourth and fifth intercostal space and when angled at 45° to the right on the left sternal border of the third and the forth intercostal space. CONCLUSIONS: Exploring areas around the left sternal border of the fourth intercostal space - where the R wave amplitudes are least affected by body positions - is a reliable method for choosing implantation locations for ILRs.

Primary Stability of a Hybrid Implant Compared with Tapered and Cylindrical Implants in an Ex Vivo Model.

BACKGROUND: Hybrid implants are thought to offer good stability and bone-implant contact. PURPOSE: This study sought to evaluate the primary stability of a hybrid implant compared with tapered and cylindrical implants in an ex vivo model and compare undersized drilling with standard drilling in attaining primary stability. MATERIALS AND METHODS: Hybrid (Straumann® Bone Level; BL), tapered (Straumann® Tapered Effect; TE), and cylindrical (Straumann® Standard Plus; SP) implants were inserted into 15 mm-thick porcine iliac crest blocks using standard (corticocancellous or cancellous bone) or undersized (cancellous bone only) drilling (n = 7). Stability was evaluated using maximum insertion torque (MIT), implant stability quotient (ISQ), and push-out tests. RESULTS: The mean MIT for BL and TE was significantly higher than that for SP (p < 0.05). With standard drilling in corticocancellous bone, the mean ISQ for TE was significantly higher than that for SP (p < .05). The mean MIT, ISQ, and push-out test scores for BL, TE, and SP with standard drilling in corticocancellous bone were significantly higher than those with undersized or standard drilling in cancellous bone (p < .05). CONCLUSIONS: In this ex vivo model, the hybrid implant demonstrated promising primary stability compared with the cylindrical implant. The improved stability of the hybrid implant was especially evident in cancellous bone. The influence of the cortical layer should be recognized when selecting implants for primary stability.

Accuracy of implant surgery with surgical guide by inexperienced clinicians: an in vitro study.

Implant surgery with surgical guide has been introduced with a concept of position improvement. The surgery might be considered as easy even for inexperienced clinician because of step simplicity. However, there are residual risks, resulting in postoperative complications. The aim of this study was to assess the accuracy of implant surgery with surgical guide by inexperienced clinicians in in vitro. After preoperative computed tomographies (CTs) of five artificial models of unilateral free-end edentulism with scan templates, five surgical guides were established from templates. Following virtual planning, 10 implants were placed in the 45 and 47 regions by five residents without any placement experiences. All drillings and placements were performed using surgical guides. After postoperative CTs, inaccurate verifications between virtual and actual positions of implants were carried out, by overlaying of pre/postoperative CT data. The angle displacement of implant axis in the 47 region was significantly larger than that in the 45 region (P = 0.031). The 3D offset of implant base in the 47 region was significantly larger than that in the 45 region (P = 0.002). For distal/apical directions, displacements of base in the 47 region were significantly larger than those in the 45 region (P = 0.004 and P = 0.003, respectively). The 3D offset of implant tip in the 47 region was significantly larger than that in the 45 region (P = 0.003). For distal/apical directions, displacements of tip in the 47 region were significantly larger than those in the 45 region (P = 0.002 and P = 0.003, respectively). Within limitations of this in vitro study, data for accuracy of implant surgery with surgical guide would be informative for further studies, because in vitro studies should be substantially made to avoid unnecessary burden of patients, in advance of retro/prospective studies. A comparison of the accuracy in this in vitro model between by inexperienced and well-experienced operators should be necessary for clinicians intending to use surgical guide for placement.

Increased expression of interleukin-6 predicts poor response to chemoradiotherapy and unfavorable prognosis in oral squamous cell carcinoma.

Recent studies have revealed that cancer cells are exacerbated by chronic inflammation. The present study examined the immunohistochemical expression for interleukin-6 (IL-6), a pleiotropic inflammatory cytokine, in oral squamous cell carcinoma (OSCC) to elucidate the association of IL-6 expression with tumor progression, chemoresistance and prognosis. Seventy-eight patients with primary OSCC were analyzed by immunohistochemical staining for IL-6. These labeling indexes (LIs) were calculated and evaluated in association with the clinicopathologic characteristics and prognosis in the OSCC patients. The patients were divided into three groups as follows: negative group = LI <5%; low IL-6 group = 5% ≤ LI <30%; high IL-6 group = LI ≥30%. The patient numbers of the negative, low and high expression groups were 24, 22 and 32, respectively. In the high IL-6 expression group, IL-6 receptor (IL-6R), phosphor-signal tranducer and activator of transcription 3 (p-STAT3) were also detected in almost all the cancer cells. The prevalence of the cervical lymph node or the distant metastasis in the high expression group was significantly higher than those in the negative and low expression groups. Furthermore, the high expression group had a significantly poorer tumor response to the preoperative chemoradiotherapy and a more unfavourable prognosis than the negative and the low expression groups. Interestingly, IL-6, IL-6R and p-STAT3 were expressed in the residual cancer cells of all the patients in the high expression group with poor response to chemoradiotherapy. These results suggested that IL-6 signaling possibly is involved in the progression and treatment-resistance of OSCC and IL-6 expression in cancer cells could be a useful predictive factor of poor response to chemoradiotherapy and unfavorable prognosis.

Possible involvement of ΔNp63 downregulation in the invasion and metastasis of oral squamous cell carcinoma via induction of a mesenchymal phenotype.

Epithelial-to-mesenchymal transition (EMT), an essential developmental program, is involved in tumor progression. ΔNp63, a homolog of p53, is associated with the EMT program, but the detailed mechanism remains to be elucidated. In this study, we investigated the role of ΔNp63 in EMT during progression of oral squamous cell carcinoma (OSCC). Five OSCC cell lines and specimens from 78 patients with OSCC were used. The expressions of ΔNp63, p63α, p63ß and epithelial markers (cytokeratins 5 and 14) was detected in the OSCC cells, but not in SQUU-B cells (high metastatic potential). E-cadherin was expressed in all OSCC cells. Mesenchymal markers were strongly expressed in the SQUU-B cells. Knockdown of endogenous ΔNp63 in HSC-2 cells induced morphological changes to the spindle shape, decreased the expression of epithelial markers, increased the expression of mesenchymal markers, increased migration and reduced proliferation. By contrast, SQUU-B cells overexpressing ΔNp63ß showed changed their morphology from stromal cell-like to epithelial cells. However, E-cadherin expression was not affected by ΔNp63 knockdown or overexpression. Immunohistochemical staining revealed that cancer cells expressing vimentin were found at the invasive front in the OSCC specimens. The intensity of ΔNp63 expression was also decreased in these cells. Interestingly, the vimentin positivity or decreased intensity of ΔNp63 was positively associated with metastases and poor prognosis in the OSCC patients. These results indicated that ΔNp63 downregulation in cancer cells induces a mesenchymal phenotype that is related to tumor progression of OSCC.