Comparing Free-Flap Reconstruction After Robot-Assisted Neck Dissection via a Retroauricular Approach and a Traditional Transcervical Approach: Single-Surgeon Experiences of 90 Consecutive Cases.

BACKGROUND: Predominant traditional approaches for most patients who have advanced-stage oral cancer with transcervical incision lines left irreversible scars. To address this, surgeons have continuously refined minimally invasive surgery (MIS) techniques, including robot-assisted neck surgeries. This article introduces and discusses the feasibility, versatility, and availability of free-flap reconstruction via the retroauricular approach (RA), considered difficult to date. METHODS: This study retrospectively analyzed 90 consecutive patients who had free-flap reconstruction performed by a single surgeon (D.K.) in the Department of Oral and Maxillofacial Surgery, Yonsei University, from March 2021 to April 2022. The type of defects and flaps, hospitalization days, total operation time, and type of vessels and anastomoses were compared statistically. RESULTS: The type of vessels used did not differ between the RA and the transcervical approach (TA) groups, nor in duration of hospital stays. Likewise, the total reconstruction time did not differ significantly between the TA group (240 min) and the RA group (245 min) (p = 0.756). However, the total operation time was about 1 h less in the TA group, a statistically significant difference (TA group [593 ± 152 min] vs. RA group [655 ± 117 min]; p = 0.044). All flaps were successful in the RA group, whereas one flap in the TA group led to a total loss (TA group [98.3%] vs. RA group [100.0%]; p = 1.000). CONCLUSIONS: Even for patients with advanced oral cancer who require massive tumor ablation, it is feasible to obtain an aesthetic and functional surgical outcome by performing free-flap reconstruction via the retroauricular approach.

Bcl-2 is a prognostic marker and its silencing inhibits recurrence in ameloblastomas.

OBJECTIVES: Ameloblastomas are the most common odontogenic epithelial tumors with high recurrence rate. The aim of this study was to identify apoptosis-related genes with recurrence of ameloblastomas and to evaluate its feasibility as a prognostic marker and as a target molecule preventing from recurrence. MATERIALS AND METHODS: Public microarray data were analyzed. To evaluate their expression in ameloblastoma patients, immunohistochemical staining was performed in 89 human ameloblastoma tissues. Quantitative PCR was performed by use of ameloblastoma cell line (AM-1). Fluorescence activated cell sorting analysis and western blotting were conducted following transfection with siRNA. Further, AM-1 cells were implanted in the renal subcapsular layer of immunodeficient mice. RESULTS: Microarray data analysis revealed that osteoprotegerin (OPG) and B-cell lymphoma 2 (Bcl-2) were the two most upregulated genes in ameloblastoma. Only Bcl-2 expression was significantly (p = 0.020) associated with recurrence in conservative treatment group (n = 17) among 89 patients. Silencing of Bcl-2 increased apoptosis in AM-1 cells in vitro and inhibited tumor nodule formation of AM-1 cells in vivo. CONCLUSION: These results suggest that Bcl-2 expression is a useful biomarker to predict recurrence of ameloblastomas, and as a therapeutic target molecule to prevent recurrence of ameloblastoma.

Considerations for Mandibular Reconstruction in the Pediatric Patient Following Resection of Malignant Tumors.

We recently achieved favorable results in 3 pediatric patients with mandibular osteosarcomas that were treated at our hospital, including with immediate reconstructive surgery performed after tumor resection. Based on a literature review and practical investigation, we discuss the considerations for mandibular reconstruction after malignant lesions are removed from the mandible in children. Mandibular reconstruction for pediatric patients requires an understanding of the changes in bone and soft-tissue architecture due to growth and development at both the donor and recipient sites. Immediate mandibular reconstruction with a free flap can be considered a reasonable option even for young children who require extensive mandibular surgery. However, the variables affecting decisions about treatment planning vary between the different conditions in individual patients, and moreover, these cases are not common in the pediatric population. Therefore, long-term follow-up treatment and further investigations are required for the optimized diagnosis, treatment, and prognosis of pediatric mandibular malignancies.

Role of microcracks in the pathogenesis of bisphosphonate-related osteonecrosis of the jaw.

OBJECTIVES: The aim of this study was to investigate the potential role of microcrack accumulation in the pathogenesis of bisphosphonate-related osteonecrosis of the jaw (ONJ) through an animal model. MATERIALS AND METHODS: Twenty-four ovariectomized rats were randomly divided into a bisphosphonate group (n = 19) and control group (n = 5) and weekly injected with zoledronic acid and normal saline, respectively. After 6 weeks, surgical intervention was performed, and the injections were continued for eight additional weeks. Then, the animals were sacrificed, and ONJ lesions were inspected for the presence of microcracks using scanning electron microscopy. Measurements included bone dimension, number of cracks, crack length, and normalized indices; crack density (Cr.Dn) and crack surface density (Cr.S.Dn) were used for group comparison. RESULTS: Both number of cracks and crack length in the bisphosphonate group were greater than those in the control group (P < 0.05). Of the 19 rats injected with bisphosphonates, 13 rats (68.4 %) were classified into the ONJ group. Cr.Dn and Cr.S.Dn were significantly greater in the ONJ group than in the non-ONJ group, indicating accumulation of unrepaired microcracks (P < 0.05). Seventy-two percent of microcracks in the ONJ group conformed to the defined length that was considered significant according to a previous literature (30-80 µm); whereas 12 % of microcracks in the non-ONJ group were considered significant (P < 0.05). CONCLUSION: Accumulation of unrepaired microcracks was significantly associated with the development of bisphosphonate-related ONJ. Further research is required to determine the role of microcracks in the pathogenesis of bisphosphonate-related ONJ. CLINICAL RELEVANCE: Long-term bisphosphonates use may deteriorate the biomechanical and physiological bone integrity, contributing to the pathogenesis of bisphosphonate-related ONJ.

Apoptotic effect of pheophorbide a-mediated photodynamic therapy on DMBA/TPA-induced mouse papillomas.

Pheophorbide a (Pa) is a chlorine-based photosensitizer, and Pa-mediated photodynamic therapy (PDT) reportedly exhibits antitumor activity against various malignancies. The aim of our study was to investigate the therapeutic effect of Pa-mediated PDT on 7,12-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorobol-13-acetate (TPA)-induced mouse papillomas. Thirty mice received a topical application of DMBA/TPA on their backs to induce mouse papillomas. One week after two sessions of Pa-mediated PDT, immunohistochemical stains and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay were performed to evaluate the apoptotic effects thereof on the papillomas. Among 63 mouse papillomas treated with Pa-mediated PDT, 17.5% of the lesions were completely removed 1 week after the first treatment, while 31.7% disappeared 1 week after the second treatment. Statistical analyses revealed significant differences in therapeutic outcomes for the Pa-mediated PDT group in comparison to a solvent-PDT group and a Pa group. Additionally, a marked downregulation of proliferating cell nuclear antigen expression, as well as upregulation of cleaved caspase 3 and cleaved poly(ADP-ribose) polymerase expression, was noted in the Pa-PDT group, compared to the solvent-PDT group and Pa group. TUNEL assay revealed higher apoptotic cell counts in the Pa-PDT group, although the difference was not statistically significant. Our data demonstrated that Pa-mediated PDT is effective in treating DMBA/TPA-induced mouse papillomas.

Combined genomic expressions as a diagnostic factor for oral squamous cell carcinoma.

Trends in genetics are transforming in order to identify differential coexpressions of correlated gene expression rather than the significant individual gene. Moreover, it is known that a combined biomarker pattern improves the discrimination of a specific cancer. The identification of the combined biomarker is also necessary for the early detection of invasive oral squamous cell carcinoma (OSCC). To identify the combined biomarker that could improve the discrimination of OSCC, we explored an appropriate number of genes in a combined gene set in order to attain the highest level of accuracy. After detecting a significant gene set, including the pre-defined number of genes, a combined expression was identified using the weights of genes in a gene set. We used the Principal Component Analysis (PCA) for the weight calculation. In this process, we used three public microarray datasets. One dataset was used for identifying the combined biomarker, and the other two datasets were used for validation. The discrimination accuracy was measured by the out-of-bag (OOB) error. There was no relation between the significance and the discrimination accuracy in each individual gene. The identified gene set included both significant and insignificant genes. One of the most significant gene sets in the classification of normal and OSCC included MMP1, SOCS3 and ACOX1. Furthermore, in the case of oral dysplasia and OSCC discrimination, two combined biomarkers were identified. The combined expression revealed good performance in the validation datasets. The combined genomic expression achieved better performance in the discrimination of different conditions than a single significant gene. Therefore, it could be expected that accurate diagnosis for cancer could be possible with a combined biomarker.

Is immediate dental implant in fibula free flap beneficial for implant survival and osteoradionecrosis in jaw reconstruction?

OBJECTIVES: This study aimed to compare the risk of osteoradionecrosis and implant survival in oral cancer patients undergoing immediate dental implants during jaw reconstruction, termed "Jaw in a Day" (JIAD), with those receiving no implants or delayed implants (non-JIAD). PATIENTS & METHODS: Clinicopathologic data were collected from prospectively enrolled JIAD patients (n = 10, 29 implants) and retrospectively from non-JIAD patients (n = 117, 86 implants). Survival analyses were performed to assess implant survival and osteoradionecrosis-free survival. RESULTS: Osteoradionecrosis occurred in 0 % of JIAD cases compared to 19.3 % in non-JIAD cases without implants and 71.4 % in non-JIAD cases with delayed implants (p = 0.008). Osteoradionecrosis-free survival was significantly better in the JIAD group than the non-JIAD group (p = 0.0059). Implants in the JIAD group all survived regardless of radiation therapy (29/29, 100 %) and 95.1 % (58/61) of implants survived in delayed implants in non-irradiated fibula without radiotherapy. Meanwhile, only 11 of 25 implants placed in irradiated fibula flaps survived, even when the implants were placed after a median time interval of 624 days after radiotherapy, and none of them were earlier than 360 days. The survival analysis revealed a significant difference (p < 0.0001). CONCLUSION: JIAD appears to offer superior outcomes in terms of implant survival and osteoradionecrosis prevention compared to delayed implant placement. Placing implants in irradiated fibula, even after years, significantly poses high risk of implant failure and osteoradionecrosis. JIAD represents a promising approach for optimal rehabilitation, particularly in oral cancer patients requiring postoperative radiotherapy. Proper positioning and orientation of implants and flaps are crucial for implant survival.

Estimating the adjuvant chemotherapy effect in elderly stage II and III colon cancer patients in an observational study.

PURPOSE: Adjuvant chemotherapy has been known as a standard treatment for patients with resected colon cancer. However, in elderly colon cancer patients, the characteristics of patients are heterogeneous with regard to life expectancy and comorbidities. Thus, with regard to the effectiveness of adjuvant chemotherapy for colon cancer, it is difficult to extrapolate data of clinical trials from the younger into the older general population. METHODS: Data for 382 elderly colon cancer patients were analyzed: 217 in Stage II and 165 in Stage III. The efficacy of adjuvant chemotherapy was evaluated in elderly colon cancer patients after a match by the propensity score method. RESULTS: For matched patients with Stage II colon cancer, there was no significant efficacy of adjuvant chemotherapy in the risk of death during all follow-up periods (P-value, 0.06-0.37). Though there was a tendency that the adjuvant chemotherapy reduces the death rate during the follow-up periods, it was not statistically significant. In the case of Stage III, the adjuvant chemotherapy was significantly effective in matched patients for 5-year (hazard ratio [HR], 0.69; 95% confidence interval [CI], 0.30-0.90) and overall survival (HR, 0.56; 95% CI, 0.34-0.94). CONCLUSIONS: Adjuvant chemotherapy for elderly patients with Stage II colon cancer is not effective, whereas elderly patients with Stage III with adjuvant chemotherapy appear to have a better survival rate in the general population.

Robot-assisted radial forearm free flap harvesting: a propensity score-matched case-control study.

Although some surgeons prefer anterolateral thigh and latissimus dorsi flap for soft tissue reconstruction in the head and neck area because it minimizes donor site complications, the radial forearm flap remains the workhorse for soft tissue reconstruction due to its reliability. To reduce donor site morbidity, the authors developed a novel technique for radial forearm flap harvesting using a robotic device. 42 radial forearm free flap reconstruction cases were studied, consisting of 31 conventional and 11 robot-assisted cases. 1:1 propensity score matching was done according to age, sex, previous and postoperative radiation therapy history and method used for vein anastomosis. There was no significant difference in flap outcome, which was 100% vitality in the robot-assisted group and 90.9% vitality in the conventional group. The robot-assisted group showed significantly longer mean harvesting time than did the conventional group, being 107.2 min and 67.0 min, respectively. Robot-assisted radial forearm flap harvesting can reduce donor site complications by minimizing incision. When more surgical experience is gained under appropriate case selection, we expect our robot-assisted method will yield a harvesting time similar to that of the conventional method and thus become more reliable and feasible.

Perforators Detected in Computed Tomography Angiography for Anterolateral Thigh Free Flap: Am I the Only One Who Feels Inaccurate?

BACKGROUND: The number, location, and pattern of perforators in anterolateral thigh(ALT) flap vary and predicting them preoperatively will aid in reconstructing complex head and neck defects. This article suggests guidelines for utilizing CTA imagery to predict perforators of ALT-free flaps. METHODS: We retrospectively analyzed 53 Korean patients who underwent reconstruction with ALT flap in our department from March 2021 to July 2022. The location, course, origin, and pedicle lengths predicted in CTA and confirmed in the operation field were recorded and compared. RESULTS: Among the 85 intraoperatively-found perforators, 79 were also identified in CTA. Six perforators unidentified in CTA were newly found intraoperatively. The positive predictive value of CTA for the perforator was 100%, with a sensitivity of 79/85 = 92.9%. Of the 79 perforators depicted by the CTA for the flap, CTA and intraoperative findings for the course were consistent in 52 cases, a 9.6 mm median discrepancy being noted between the actual location and CTA. CONCLUSIONS: The overall pattern or location of perforation was not significantly different between the two, although some differences were observed. It is suggested that the addition of Doppler imaging, in conjunction with CTA, can aid in perforator detection and help minimize such discrepancies.

Which risk factors are associated with neurosensory deficits of inferior alveolar nerve after mandibular third molar extraction?

PURPOSE: Mandibular third molar extraction is a commonly performed procedure and is recognized as a relatively frequent cause of inferior alveolar nerve (IAN) injury. The aim of the present study was to investigate the specific risk factors for neurosensory deficits, including age, gender, impaction depth, angulation of the third molar, and various radiographic superimposition signs. MATERIALS AND METHODS: In a case-control study of patients who had undergone mandibular third molar extraction, a case group was developed of patients showing neurosensory deficits of the IAN, and a control group was formed of randomly selected patients without any neurosensory symptoms. Bivariate analyses were performed to assess the relationship between each variable and IAN injury. A multivariate logistic regression model was used to compute the odds ratios, P values, and predictive values of the radiographic superimposition signs. RESULTS: Of 12,842 total patients, the study group included 104 cases and 135 controls. The results indicated that older age and deeper impaction status were significant risk factors (P < .05). Darkening of the roots, deflection of the roots, narrowing of the roots, dark and bifid apexes of the roots, and narrowing of the canal were also significant risk factors. The positive predictive values ranged from 0.7% to 6.9% and the negative predictive values from 99% to 100%, with adjustment for the definitive prevalence of IAN injury (0.81%, 104/12,842 patients). However, the relatively low positive predictive value renders questionable the predictability of superimposition signs on orthopantomography. In the absence of specific radiographic signs, the risk of neurosensory deficit of the IAN could be negligible. The sensory symptoms disappeared after 6 months in 92.3% of the patients and 98.1% showed recovery after 1 year. CONCLUSIONS: The results of the present study have demonstrated a significant association between several risk factors and neurosensory deficits of the IAN after third molar extraction. With a case group of 104 patients, the number of subjects was significantly greater than that in previous studies, increasing the reliability of these results.

Risk factor analysis of dental implants in patients with irradiated head and neck cancer.

BACKGROUND: We investigated dental implant outcomes in patients who had previously received radiotherapy (RT) for head and neck malignancies. METHODS: We reviewed 90 dental implants in 27 patients who received RT for head and neck cancer and received dental implants afterwards. The cumulative implant survival rate (CISR) was calculated. In addition, the implant quality was assessed using "Health Scale for Dental Implants." RESULTS: The CISR at 3 years was 79.6%. The mean radiation dose at the implant site (Dmean ) was identified as an independent prognostic factor for implant survival. No implant failed if Dmean was less than 38 Gy. Regarding implant quality, dental implants in grafted bone and Dmean were independent risk factors. CONCLUSIONS: Dmean was identified as an independent prognostic factor for implant survival and quality. Dental implants can be safely considered when Dmean is lower than 38 Gy.

Risk Factors of Microscopically Tumor-Free Surgical Margins for Recurrence and Survival of Oral Squamous Cell Carcinoma Patients.

Objectives: The concept of adequate surgical margins remains controversial in oral squamous cell carcinoma (OSCC) surgery. This study aimed to identify surgical margin-related indicators that might impact recurrence and survival of OSCC patients. Materials and Methods: Histopathological examination was performed using hematoxylin-eosin-stained surgical margin tissue sections in 235 OSCC patients. Axin2 and Snail expression at the surgical margin was detected by immunohistochemistry. The impact of the Axin2-Snail cascade on tumorigenesis of the immortalized human oral keratinocyte (IHOK) line was investigated in vivo. Results: The width and dysplasia of surgical margins were not significantly associated with the outcome of OSCC patients. In a multivariate analysis using variable clinicopathologic factors and with Axin2 and Snail expression as cofactors, higher age (hazard ratio [HR]:1.050; P=0.047), Axin2 (HR:6.883; P=0.014), and Snail abundance (HR:5.663; P=0.009) had independent impacts on worsened overall survival. Similarly, lesion site in retromolar trigone (HR:4.077; P=0.010), upper (HR:4.332; P=0.005) and lower gingiva (HR:3.545; P=0.012), presence of extranodal extension (HR:9.967; P<0.001), perineural invasion (HR:3.627; P=0.024), and Snail abundance (HR:3.587; P<0.001) had independent impacts on worsened recurrence-free survival. Furthermore, Axin2 knockdown induced decreased Snail expression and attenuated tumorigenesis in the IHOK line. Conclusion: Histopathological examination of surgical margins may not be reliable to predict OSCC patient outcome. Molecular analysis may provide a more accurate risk assessment of surgical margins in OSCC. In particular, Axin2 and Snail are potential predictive biomarkers for the risk assessment of surgical margins in OSCC.

Hepatic differentiation from human embryonic stem cells using stromal cells.

OBJECTIVE: The derivation of hepatocytes from human embryonic stem (hES) cells is of value both in the study of early human liver organogenesis and in the creation of an unlimited source of donor cells for hepatocyte transplantation therapy. Here, we report the generation of hepatocyte-like cells derived from hES cells. METHODS: Hepatic endoderm cells were generated by adding activin A for 5 d- to 1-d-old embryoid bodies formed from hES cells. The hepatic endoderm cells were cocultured with mitomycin treated 3T3-J2 feeder cells. RESULTS: After co-culture with mitomycin treated 3T3-J2 feeder cells, these hepatic endodermal cells yielded hepatocyte-like cell colonies, which possessed the proliferation potential to be cultured for an extended period of more than 30 d. With extensive expansion, they co-expressed the hepatic marker AFP and albumin, indicating that they were hepatocyte-like cells. CONCLUSIONS: We report the generation of proliferative hepatocyte-like cells from hES cells. These hES cell derived hepatic cells can effectively be used as in vitro model for studying the mechanisms of hepatic stem/progenitor cell origin, self-renewal and differentiation.

Posterior maxillary segmental osteotomy concomitant with sinus lift using a piezoelectric device.

Tooth loss evokes functional and esthetic problems, and adjacent teeth can move if they are not corrected in a timely manner, rendering the problems of restoring the dentition more complex. If the opposing tooth is consequently extruded, several treatment modalities may be adopted, such as occlusal adjustment, crown prosthesis, orthodontic treatment, and segmental osteotomy. Segmental osteotomy is the most aggressive and invasive treatment for restoring a problematic occlusal plane due to the complications, such as hemorrhage, loss of tooth vitality, or necrosis of the segment. Piezoelectric devices have recently been used in oral surgery and implant dentistry because they preserve the soft tissue. In this report, we describe a bilateral posterior segmental osteotomy procedure to correct a collapsed occlusal plane with sinus mucosa elevation, using piezoelectric devices to preserve the integrity of the sinus membrane and the posterior superior alveolar artery.

Analysis of adjacent fracture after percutaneous vertebroplasty: does intradiscal cement leakage really increase the risk of adjacent vertebral fracture?

OBJECTIVE: The purpose of this study was to evaluate the incidence and risk factors associated with adjacent vertebral fracture after percutaneous vertebroplasty (PVP) to treat osteoporotic vertebral compression fractures. We also investigated the effect of intradiscal cement leakage on adjacent vertebral fracture formation after PVP. MATERIALS AND METHODS: From January 2003 to March 2009, 188 patients (163 women, 25 men; mean age, 70.9 years; range, 42-92 years) who underwent 214 PVP sessions at 351 levels for osteoporotic vertebral compression fractures were retrospectively enrolled in this study. The effect of intradiscal cement leakage on new adjacent vertebral fracture formation after PVP was evaluated. Possible other risk factors were also analyzed using univariate and multivariate methods. The risk factors included age, gender, mean bone mineral density (BMD), the vertebral level treated, presence of an intravertebral cleft or cyst before treatment, kyphosis angle, wedge angle, and the injected cement volumes. RESULTS: During the follow-up periods, new adjacent vertebral fractures developed in 36 (10.3%) of 351 treated levels. For 91 (25.9%) levels, intradiscal cement leakage was detected on procedural fluoroscopic radiographs. There was no statistically significant association between intradiscal cement leakage and new adjacent vertebral compression fracture (p = 0.789). Among the other risk factors, only the vertebral levels treated, especially the thoracolumbar junction, showed a significant relationship to new adjacent vertebral fractures (univariate analysis, p = 0.037; multivariate analysis, p = 0.043). CONCLUSIONS: Intradiscal cement leakage does not seem to be related to subsequent adjacent vertebral compression fracture in patients who underwent PVP for treatment of an osteoporotic compression fracture. The thoracolumbar location of the initial compression fracture is the only factor correlated with an adjacent vertebral fracture after PVP.

Handheld Near-Infrared Fluorescence Imaging Device Using Modified Action Cameras for Peri-Operative Guidance of Microvascular Flap Surgery.

Indocyanine green near-infrared fluorescence (ICG-NIRF) imaging has recently come into use as a novel method in peri-operative microvascular flap assessment. However, a majority of the many commercial devices launched for clinical use lack mobility, portability, and cost-efficiency and are thus unsuitable for intra-oral applications. This study introduces a cost-effective, customized, handheld NIRF device following principles of ICG-NIRF imaging. Moreover, the novel characteristics of our prototype, considered in conjunction with a literature review highlighting the significance of fluorescence devices in microvascular surgery, point to a new generation of devices for use in microvascular flap surgery.

Effects of pre-extraction intermittent PTH administration on extraction socket healing in bisphosphonate administered ovariectomized rats.

The purpose of this study was to investigate the effect of administering intermittent parathyroid hormone (iPTH) before tooth extraction versus after tooth extraction on the risk of developing MRONJ in experimental animal model. Twenty-five ovariectomized rats received 6 weeks of bisphosphonate therapy. They were classified into 3 groups, based on the timing of the medication, as Control, Pre-PTH and Post-PTH groups. For Control group, normal saline was administered before and after tooth extraction. iPTH was administered during 4 weeks before tooth extraction for Pre-PTH group and after tooth extraction for Post-PTH group. The animals were euthanized 8 weeks after tooth extraction. Macroscopic, histological, micro-computed tomography (micro-CT), and histomorphometric examinations were conducted. The incidences of impaired healing were 11.11% both in Pre-PTH and Post-PTH groups, which was lower than the Control group (42.86%). Bone healing in the extraction socket, based on micro-CT and histomorphometry evaluations, was best in Post-PTH and worst in Control group. The Pre-PTH group showed moderate healing pattern. Despite of limitations in this study, the authors identified Pre-PTH group seems to have positive effect on extraction socket healing. With regard to timing, administering iPTH after tooth extraction was superior to applying it before tooth extraction.