Robot-Assisted Retroauricular Anterior Scalenectomy for Neurogenic Thoracic Outlet Syndrome

Background@#This study described the surgical technique of a robot-assisted retroauricular anterior scalenectomy and assessed clinical outcomes and complications for patients with neurogenic thoracic outlet syndrome (nTOS). @*Methods@#Between February 2014 and August 2016, 5 patients underwent robot-assisted retroauricular anterior scalenectomy using the da Vinci Xi system for nTOS. For clinical assessment, visual analog scale (VAS) symptom score, pinch and grip strength, and disabilities of arm, shoulder and hand (DASH) score were assessed to compare preoperative and postoperative outcomes. Postoperative complications were also reviewed. @*Results@#The VAS symptom, pinch and grip strength, and DASH scores improved 1 year after the operation. All patients were satisfied with the surgical scars. Temporary postoperative complications, which spontaneously resolved within 3 months, were noticed in 2 patients: one with vocal cord palsy and the other with upper brachial plexus palsy. @*Conclusions@#The robot-assisted retroauricular anterior scalenectomy for patients with nTOS seems feasible and safe, providing satisfactory cosmetic results.

Protective Effect of Locally Injected Polydeoxyribonucleotide in Ischemic Murine Random Skin Flaps / 대한이비인후과학회지

Background and Objectives@#This study aimed to investigate the protective effect of polydeoxyribonucleotide (PDRN) against skin flap necrosis in a murine skin flap model.Materials and Method Twenty mice with rectangular skin flaps on the dorsum were randomly divided into the PDRN (n=10) and pentobarbital sodium (PBS) (n=10) injection groups. PDRN (8 mg/kg) was subdermally injected at 12 different points immediately after the operation. After 7 days, the flap perfusions were evaluated using a laser speckle contrast imaging (LSCI) system, and specimens were collected for immunohistochemistry analysis. @*Results@#The percentage of survival area relative to the total flap area was significantly higher in the PDRN group (60.87%±7.63%) than in the PBS group (45.23%±10.72%) (p<0.05). The mean LSCI perfusion signal of the distal part of the skin flap in the PBS group was 0.57±0.12, and that in the PDRN group was 0.74±0.13 (p<0.05). The PDRN group had a significantly lower interleukin 1 beta expression than the PBS group and higher vascular endothelial growth factor α expression than the PBS group (p<0.05). @*Conclusion@#These findings suggest that subdermally injected PDRN is more effective in enhancing flap survival during necrosis.

Methodology in Conventional Head and Neck Reconstruction Following Robotic Cancer Surgery:A Bridgehead Robotic Head and Neck Reconstruction

Purpose@#Robotic head and neck surgery is widespread nowadays. However, in the reconstruction field, the use of robotic operations is not. This article aimed to examine methodologies for conventional head and neck reconstruction after robotic tumor surgery in an effort to obtain further options for future reconstruction manipulations. @*Materials and Methods@#A retrospective review of all patients who received head and neck robot surgery and conventional reconstructive surgery between October 2016 and September 2021. @*Results@#In total, 53 cases were performed. 67.9% of the tumors were greater than 4 cm. Regarding defect size, 47.2% of the lesions were greater than 8 cm. In terms of TNM stage, stage 3 disease was recorded in 26.4% and stage 4 in 52.8%. To make a deep and narrow field wider, we changed the patient’s posture in pre-op field, additional dissection was done. We used radial forearm flap mostly (62.2%). @*Conclusion@#Conventional head and neck reconstruction after robotic ENT cancer surgery is possible. One key step is to secure additional space in the deep and narrow space left after robotic surgery. For this, we opted for a radial forearm flap mostly. This can be performed as a bridgehead to perform robotic head and neck reconstruction.

Machine Learning-Based Predictor for Treatment Outcomes of Patients With Salivary Gland Cancer After Operation / 대한이비인후과학회지

Background and Objectives@#The purpose of this study was to analyze the survival data of salivary gland cancer (SGCs) patients to construct machine learning and deep learning models that can predict survival and use them to stratify SGC patients according to risk estimate.Subjects and Method We retrospectively analyzed the clinicopathologic data from 460 patients with SGCs from 2006 to 2018. @*Results@#In Cox proportional hazard (CPH) model, pM, stage, lymphovascular invasion, lymph node ratio, and age exhibited significant correlation with patient’s survival. In the CPH model, the c-index value for the training set was 0.85, and that for the test set was 0.81. In the Random Survival Forest model, the c-index value for the training set was 0.86, and that for the test set was 0.82. Stage and age exhibited high importance in both the Random Survival Forest and CPH models. In the deep learning-based model, the c-index value was 0.72 for the training set and 0.72 for the test set. Among the three models mentioned above, the Random Survival Forest model exhibited the highest performance in predicting the survival of SGC patients. @*Conclusion@#A survival prediction model using machine learning techniques showed acceptable performance in predicting the survival of SGC patients. Although large-scale clinical and multicenter studies should be conducted to establish more powerful predictive model, we expect that individualized treatment can be realized according to risk stratification made by the machine learning model.

Clinico-pathologic Factors and Machine Learning Algorithm for Survival Prediction in Parotid Gland Cancer / 대한두경부종양학회지

Background/Objectives@#This study analyzed the prognostic significance of clinico-pathologic factors including comprehensive nodal factors in parotid gland cancers (PGCs) patients and constructed a survival prediction model for PGCs patients using machine learning techniques.Materials & Methods: A total of 131 PGCs patients were enrolled in the study. @*Results@#There were 19 cases (14.5%) of lymph nodes (LNs) at the lower neck level and 43 cases (32.8%) involved multiple level LNs metastases. There were 2 cases (1.5%) of metastases to the contralateral LNs. Intraparotid LNs metastasis was observed in 6 cases (4.6%) and extranodal extension (ENE) findings were observed in 35 cases (26.7%). Lymphovascular invasion (LVI) and perineural invasion findings were observed in 42 cases (32.1%) and 49 cases (37.4%), respectively. Machine learning prediction models were constructed using clinico-pathologic factors including comprehensive nodal factors and Decision Tree and Stacking model showed the highest accuracy at 74% and 70% for predicting patient’s survival. @*Conclusion@#Lower level LNs metastasis and LNR have important prognostic significance for predicting disease recurrence and survival in PGCs patients. These two factors were used as important features for constructing machine learning prediction model. Our machine learning model could predict PGCs patient’s survival with a considerable level of accuracy.

Comprehensive Analysis of Clinicopathologic Factors Predictive of an Unfavorable Prognosis in Patients With Acinic Cell Carcinoma of the Parotid Gland

Objectives@#. In subset of patients, acinic cell carcinoma (AcCC) exhibits aggressive features such as recurrence, distant metastasis, and mortality. This study aimed to investigate clinicopathologic factors influencing patients’ prognosis and to identify adverse features predictive of an unfavorable prognosis. @*Methods@#. Between January 2000 and December 2016, 59 patients with AcCC were enrolled in this study. @*Results@#. The patients’ 5-year overall survival rate was 93.3%, and their 5-year recurrence-free survival rate was 80.5%. During the study period, recurrence occurred in 10 patients. The mean time to recurrence after surgery was 26 months (range, 5–60 months). During the study period, three patients died from the disease. Univariate analysis showed that sex, surgical extent, extranodal extension, T classification, and TNM stage were significantly associated with disease recurrence. Multivariate analysis showed that, among the clinicopathologic factors included in the analysis, only TNM stage displayed a statistically significant correlation with disease recurrence. @*Conclusion@#. Surgical treatment alone yielded good results for AcCC, and additional treatment did not affect the recurrence-free survival rate or the overall survival rate, even when the resection margin was less than 1 mm. Other pathologic factors did not show prognostic significance for disease recurrence or death.

Analysis of PD-L1 expression in salivary duct carcinoma with its efficacy as a tumor marker / 대한두경부종양학회지

BACKGROUND/OBJECTIVES: Despite multiple approaches of treatments for salivary duct carcinoma, there has been a need for more successful treatment methods because of its poor prognosis. Treatment options like immunotherapy using new technologies have been attempted. Based on recent study results indicating that targeting programmed death receptors are effective in treating various cancers, this study aimed to identify the frequency of PD-L1 expression and its impact on survival rate in salivary duct carcinoma.MATERIALS #SPCHAR_X0026; METHODS: We studied 33 patients with salivary gland cancer who were available for histologic specimens. We examined the expression of PD-L1 in the tissues and analyzed the association with the survival rate and the association with various clinical parameters.RESULTS: According to this study and review of similar studies, we discovered that the expression of PD-L1 in salivary duct carcinoma was lower than other types of cancers. The impact of PD-L1 on survival rate also showed inconsistency in salivary duct carcinoma.CONCLUSION: Immunotherapy by PD-1/PD-L1 checkpoint blockade in salivary duct carcinoma needs further evaluation for clinical application.

Survival and Functional Outcome after Treatment for Primary Base of Tongue Cancer: A Comparison of Definitive Chemoradiotherapy versus Surgery Followed by Adjuvant Radiotherapy / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study was to compare the clinical and functional outcomes in patients with primary base of tongue (BOT) cancer who received definitive radiotherapy (RT) or surgery followed by radiotherapy (SRT). MATERIALS AND METHODS: Between January 2002 and December 2016, 102 patients with stage I-IVB primary BOT cancer underwent either definitive RT (n=46) or SRT (n=56), and treatment outcomes were compared between two groups. The expression of p16 was also analyzed. RESULTS: The RT group had more patients with advanced T stage (T3-4) disease (58.7% vs. 35.7%, p=0.021) and who received chemotherapy (91.3% vs. 37.5%, p < 0.001) than the SRT group. At a median follow up of 36.9 months (range, 3.3 to 181.5 months), the 5-year overall survival (OS) and disease-free survival (DFS) were 75.5% and 68.7%, respectively. With respect to treatment group, the 5-year OS and DFS in the RT and SRT groups did not differ significantly (OS, 68.7% vs. 80.5%, p=0.601; DFS, 63.1% vs. 73.1%, p=0.653). In multivariate analysis, OS differed significantly according to p16 expression (p16-negative vs. p16-positive; hazard ratio [HR], 0.145; 95% confidence interval [CI], 0.025 to 0.853; p=0.033). Regarding DFS, p16 expression (p16-negative vs. p16-positive; HR, 0.164; 95% CI, 0.045 to 0.598; p=0.006) showed a significant effect in multivariate analysis. Functional defects (late grade ≥ 3 dysphagia or voice alteration) were more frequently reported in the SRT than in the RT group (16.1% vs. 2.2%, p=0.021). CONCLUSION: Despite advanced disease, patients in the RT group showed comparable survival outcomes and better functional preservation than those in the SRT group.

Incorporating a continuous suction system as a preventive measure against fistula-related complications in head and neck reconstructive surgery

BACKGROUND: Although previous studies have focused on determining prognostic and causative variables associated with fistula-related complications after head and neck reconstructive surgery, only a few studies have addressed preventive measures. Noting that pooled saliva complicates wound healing and precipitates fistula-related complications, we devised a continuous suction system to remove saliva during early postoperative recovery. METHODS: A continuous suction system was implemented in 20 patients after head and neck reconstructive surgery between January 2012 and October 2017. This group was compared to a control group of 16 patients at the same institution. The system was placed orally when the lesion was on the anterior side of the retromolar trigone area, and when glossectomy or resection of the mouth floor was performed. When the orohypopharynx and/or larynx were eradicated, the irrigation system was placed in the pharyngeal area. RESULTS: The mean follow-up period was 9.2±2.4 months. The Hemovac system was applied for an average of 7.5 days. On average, 6.5 days were needed for the net drain output to fall below 10 mL. Complications were analyzed according to their causes and rates. A fistula occurred in two cases in the suction group. Compared to the control group, a significant difference was noted in the surgical site infection rate (P < 0.031). CONCLUSIONS: Clinical observations showed reduced saliva pooling and a reduction in the infection rate. This resulted in improved wound healing through the application of a continuous suction system.

Tumor Stage-Related Role of Radiotherapy in Patients with an External Auditory Canal and Middle Ear Carcinoma / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study was to evaluate the clinical outcomes of patients treated with radiotherapy (RT) for a carcinoma of the external auditory canal (EAC) and middle ear. MATERIALS AND METHODS: The records of 32 patients who received RT from 1990 to 2013 were reviewed retrospectively. The Pittsburgh classification was used to stage all the cancers (early stage, T1/T2 [n=12]; advanced stage, T3/T4 or N positive [n=20]). Twenty-one patients (65.6%) were treated with postoperative RT and 11 patients (34.4%) were treated with definitive RT. The median radiation doses for postoperative and definitive RT were 60 Gy and 64.8 Gy, respectively. Chemotherapy was administered to seven patients (21.9%). RESULTS: The 5-year overall survival and disease-free survival rates for all patients were 57% and 52%, respectively. The disease control rates for the patients with early stage versus advanced stage carcinomawere 55.6% (5/9) and 50% (6/12) in the postoperative RT group and 66.7% (2/3) and 37.5% (3/8) in the definitive RT group, respectively. Overall, 15 cases (14 patients, 46.7%) experienced treatment failure; these failures were classified as local in four cases, regional in one case, and distant in 10 cases. The median follow-up period after RT was 51 months (range, 7 to 286 months). CONCLUSION: Patients with early stage carcinoma achieved better outcomes when definitive RT was used. Advanced stage carcinoma patients experienced better outcomes with postoperative RT. The high rate of distant failure after RT, with or without surgery, reflected the lack of a consensus regarding the best therapeutic approach for treating carcinoma of the EAC and middle ear.

Comparative Effects of Non-Thermal Atmospheric Pressure Plasma on Migration and Invasion in Oral Squamous Cell Cancer, by Gas Type

PURPOSE: The fourth state of matter, plasma is known as an ionized gas with electrons, radicals and ions. The use of non-thermal plasma (NTP) in cancer research became possible because of the progresses in plasma medicine. Previous studies on the potential NTP-mediated cancer therapy have mainly concentrated on cancer cell apoptosis. In the present study, we compared the inhibitory effect of NTP on cell migration and invasion in the oral squamous cancer cell lines. MATERIALS AND METHODS: We used oral squamous cancer cell lines (SCC1483, MSKQLL1) and different gases (N₂, He, and Ar). To investigate the mechanism of plasma treatment, using different gases (N₂, He, and Ar) which induces anti-migration and anti-invasion properties, we performed wound healing assay, invasion assay and gelatin zymography. RESULTS: The results showed that NTP inhibits cancer cell migration and invasion of oral squamous cancer cell. In addition, focal adhesion kinase expression and matrix metalloproteinase-2/9 activity were also inhibited. CONCLUSION: The suppression of cancer cell invasion by NTP varied depending on the type of gas. Comparison of the three gases revealed that N₂ NTP inhibited cell migration and invasion most potently via decreased expression of focal adhesion kinase and matrix metalloproteinase activity.

Robot-assisted submandibular gland excision via modified facelift incision / 대한악안면성형재건외과학회지

BACKGROUND: The conventional transcervical resection for submandibular gland disease has some risks and an unsatisfactory cosmetic result. Recently, robot-assisted surgery has been developed as a plausible substitute for conventional surgery which provides an excellent cosmetic outcome. CASE PRESENTATION: The authors performed robot-assisted sialadenectomy via modified facelift incision using the da Vinci Xi surgical system (Intuitive Surgical Inc., CA, USA) with two endowrist arms (monopolar curved scissors and Maryland bipolar forceps) successfully in a 44-year-old female patient who suffered from sialolith and severe atrophic submandibular gland. CONCLUSIONS: If similar studies are done in the future, this robot-assisted sialadenectomy may become established as an alternative to existing disadvantageous surgical methods.

Anterolateral Thigh Thickness Measurement in Positron Emission Tomography-Computed Tomography for the Prediction of Free Flap Reconstruction Outcomes in Head and Neck Cancer / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Anterolateral thigh (ALT) flaps are commonly used for head and neck surgery reconstruction. However, a thick ALT often leads to long operation times. Therefore, ALT thickness on a preoperative non contrast image of positron emission tomography-computed tomography (PET-CT) scan was measured to predict surgical outcome. SUBJECTS AND METHOD: The correlation between ALT thickness and total reconstruction time was analyzed in 106 patients. The differences in ALT thickness between the successful and compromised-flap groups were analyzed retrospectively. RESULTS: Median ALT thickness was 4.49 mm, and total reconstruction time was 190 min. Total reconstruction time was significantly correlated with ALT thickness (p=0.019). ALT thickness, body mass index (BMI), total reconstruction time and ischemia time were significantly greater in the compromised-flap group than in the successful group. In the multivariate analysis, only BMI and ischemia time were predictors for the compromised flap. CONCLUSION: ALT thickness measured on a non-contrast image of PET-CT scan is useful as a surgical outcome predictor with respect to total reconstruction time. A further study may suggest the risk of a thick ALT in a compromised flap in head and neck reconstruction using an ALT free flap.

Hypoxia Induces Epithelial-Mesenchymal Transition in Follicular Thyroid Cancer: Involvement of Regulation of Twist by Hypoxia Inducible Factor-1alpha

PURPOSE: Although follicular thyroid cancer (FTC) has a relatively fair prognosis, distant metastasis sometimes results in poor prognosis and survival. There is little understanding of the mechanisms contributing to the aggressiveness potential of thyroid cancer. We showed that hypoxia inducible factor-1alpha (HIF-1alpha) induced aggressiveness in FTC cells and identified the underlying mechanism of the HIF-1alpha-induced invasive characteristics. MATERIALS AND METHODS: Cells were cultured under controlled hypoxic environments (1% O2) or normoxic conditions. The effect of hypoxia on HIF-1alpha, and epithelial-to-mesenchymal transition (EMT) related markers were evaluated by quantitative real-time PCR, Western blot analysis and immunocytochemistry. Invasion and wound healing assay were conducted to identify functional character of EMT. The involvement of HIF-1alpha and Twist in EMT were studied using gene overexpression or silencing. After orthotopic nude mouse model was established using the cells transfected with lentiviral shHIF-1alpha, tissue analysis was done. RESULTS: Hypoxia induces HIF-1alpha expression and EMT, including typical morphologic changes, cadherin shift, and increased vimentin expression. We showed that overexpression of HIF-1alpha via transfection resulted in the aforementioned changes without hypoxia, and repression of HIF-1alpha with RNA interference suppressed hypoxia-induced HIF-1alpha and EMT. Furthermore, we also observed that Twist expression was regulated by HIF-1alpha. These were confirmed in the orthotopic FTC model. CONCLUSION: Hypoxia induced HIF-1alpha, which in turn induced EMT, resulting in the increased capacity for invasion and migration of cells via regulation of the Twist signal pathway in FTC cells. These findings provide insight into a possible therapeutic strategy to prevent invasive and metastatic FTC.

The Korean guideline for thyroid cancer screening

Thyroid cancer is the most common malignancy in Korea; in 2012, about 44,000 new cases (19.6% of all malignancies) were registered and the estimated age-standardized incidence rate of thyroid cancer was 73.6 per 100,000 (17.3 and 88.6 per 100,000 in men and women, respectively). Despite the steep increase in its incidence, the age-standardized mortality rate of thyroid cancer has remained stable and 10-year relative survival rate is 99.2%. Increased detection using high-resolution ultrasonography may have contributed to the increased incidence of thyroid cancer if not all. However, the effectiveness of thyroid cancer screening using ultrasonography has not been fully evaluated as to whether screening and early diagnosis could decrease the morbidity or mortality of thyroid cancer. A multidisciplinary expert committee for developing a guideline for thyroid cancer screening was organized and established a recommendation for thyroid cancer screening using ultrasonography in Korea based on scientific evidence for the first time. In conclusion, the current evidence is insufficient to assess the balance of benefits and harms of the thyroid cancer screening by ultrasonography and the recommendation is that thyroid ultrasonography is not routinely recommended for healthy subjects.

Predictors of Thyroid Gland Involvement in Hypopharyngeal Squamous Cell Carcinoma

PURPOSE: Decision to perform concurrent ipsilateral thyroidectomy on patients with hypopharyngeal cancer is important, and unnecessary thyroidectomy should be avoided if oncologically feasible. We hypothesized that concurrent ipsilateral thyroidectomy is not routinely required to prevent occult metastasis. This study aimed to determine the prevalence of histological thyroid invasion in patients with hypopharyngeal cancer, and to refine the indications for prophylactic ipsilateral thyroidectomy in patients with hypopharyngeal cancer. MATERIALS AND METHODS: A retrospective review of the medical records from the Department of Otolaryngology at Yonsei University College of Medicine was conducted from January 1994 to December 2009. A total of 49 patients underwent laryngopharyngectomy with thyroidectomy as a primary treatment of hypopharyngeal cancer. RESULTS: The incidence of thyroid gland involvement was 10.2%. The most common route of invasion was direct extension through the thyroid cartilage. Thyroid cartilage invasion (p=0.034) was the most significant factor associated with thyroid invasion. Disease-specific survival at 5 years was lower in patients with than without thyroid gland invasion (26.7% vs. 55.2%, respectively; p=0.032). Disease-free survival at 5 years was also lower in patients with than without thyroid gland invasion (20.0% vs. 52.1%, respectively; p=0.024). CONCLUSION: Ipsilateral thyroidectomy in combination with total laryngopharyngectomy is indicated when invasion of the thyroid cartilage is suspected in patients with hypopharyngeal cancer.

Postoperative radiotherapy in salivary ductal carcinoma: a single institution experience

PURPOSE: We reviewed treatment outcomes and prognostic factors for patients with salivary ductal carcinoma (SDC) treated with surgery and postoperative radiotherapy from 2005 to 2012. MATERIALS AND METHODS: A total of 16 patients were identified and 15 eligible patients were included in analysis. Median age was 61 years (range, 40 to 71 years) and 12 patients (80%) were men. Twelve patients (80%) had a tumor in the parotid gland, 9 (60%) had T3 or T4 disease, and 9 (60%) had positive nodal disease. All patients underwent surgery and postoperative radiotherapy. Postoperative radiotherapy was delivered using 3-dimensional conformal radiotherapy or intensity-modulated radiotherapy. Locoregional failure-free survival (LRFFS), distant failure-free survival (DFFS), progression-free survival (PFS), and overall survival (OS) were calculated using the Kaplan-Meier method. Differences in survival based on risk factors were tested using a log-rank test. RESULTS: Median total radiotherapy dose was 60 Gy (range, 52.5 to 63.6 Gy). Four patients received concurrent weekly chemotherapy with cisplatin. Among 10 patients who underwent surgery with neck dissection, 7 received modified radical neck dissection. With a median follow-up time of 38 months (range, 24 to 105 months), 4-year rates were 86% for LRFFS, 51% for DFFS, 46% for PFS, and 93% for OS. Local failure was observed in 2 patients (13%), and distant failure was observed in 7 (47%). The lung was the most common involved site of distant metastasis. CONCLUSION: Surgery and postoperative radiotherapy in SDC patients resulted in good local control, but high distant metastasis remained a major challenge.

A Novel Synthetic Compound 3-Amino-3-(4-Fluoro-Phenyl)-1H-Quinoline-2,4-Dione (KR22332) Exerts a Radioprotective Effect via the Inhibition of Mitochondrial Dysfunction and Generation of Reactive Oxygen Species

PURPOSE: Acute side effects of radiation such as oral mucositis are observed in most patients. Although several potential radioprotective agents have been proposed, no effective agent has yet been identified. In this study, we investigated the effectiveness of synthetic compound 3-amino-3-(4-fluoro-phenyl)-1H-quinoline-2,4-dione (KR22332) as a radioprotective agent. MATERIALS AND METHODS: Cell viability, apoptosis, the generation of reactive oxygen species (ROS), mitochondrial membrane potential changes, and changes in apoptosis-related signaling were examined in human keratinocyte (HaCaT). RESULTS: KR22332 inhibited irradiation-induced apoptosis and intracellular ROS generation, and it markedly attenuated the changes in mitochondrial membrane potential in primary human keratinocytes. Moreover, KR22332 significantly reduced the protein expression levels of ataxia telangiectasia mutated protein, p53, and tumor necrosis factor (TNF)-alpha compared to significant increases observed after radiation treatment. CONCLUSION: KR22332 significantly inhibited radiation-induced apoptosis in human keratinocytes in vitro, indicating that it might be a safe and effective treatment for the prevention of radiation-induced mucositis.

A Novel Synthetic Compound 3-Amino-3-(4-Fluoro-Phenyl)-1H-Quinoline-2,4-Dione (KR22332) Exerts a Radioprotective Effect via the Inhibition of Mitochondrial Dysfunction and Generation of Reactive Oxygen Species

PURPOSE: Acute side effects of radiation such as oral mucositis are observed in most patients. Although several potential radioprotective agents have been proposed, no effective agent has yet been identified. In this study, we investigated the effectiveness of synthetic compound 3-amino-3-(4-fluoro-phenyl)-1H-quinoline-2,4-dione (KR22332) as a radioprotective agent. MATERIALS AND METHODS: Cell viability, apoptosis, the generation of reactive oxygen species (ROS), mitochondrial membrane potential changes, and changes in apoptosis-related signaling were examined in human keratinocyte (HaCaT). RESULTS: KR22332 inhibited irradiation-induced apoptosis and intracellular ROS generation, and it markedly attenuated the changes in mitochondrial membrane potential in primary human keratinocytes. Moreover, KR22332 significantly reduced the protein expression levels of ataxia telangiectasia mutated protein, p53, and tumor necrosis factor (TNF)-alpha compared to significant increases observed after radiation treatment. CONCLUSION: KR22332 significantly inhibited radiation-induced apoptosis in human keratinocytes in vitro, indicating that it might be a safe and effective treatment for the prevention of radiation-induced mucositis.

Effect of Endogenous Bone Marrow Derived Stem Cells Induced by AMD-3100 on Expanded Ischemic Flap

The purpose of this study was to devise an expanded ischemic flap model and to investigate the role of AMD-3100 (Plerixafor, chemokine receptor 4 inhibitor) in this model by confirming its effect on mobilization of stem cells from the bone marrow. Male Sprague-Dawley rats were used as an animal research model. The mobilization of stem cells from the bone marrow was confirmed in the AMD-3100-treated group. The fractions of endothelial progenitor cells (EPC) and the vascular endothelial growth factor receptor (VEGFR) 2+ cells in the peripheral blood were increased in groups treated with AMD-3100. The expression of vascular endothelial growth factor (VEGF) was increased in response to expansion or AMD injection. The expression of stromal cell derived factor (SDF)-1 and VEGFR2 were increased only in unexpanded flap treated with AMD-3100. Treatment with AMD-3100 increased both the number and area of blood vessels. However, there were no statistically significant differences in the survival area or physiologic microcirculation in rats from the other groups. This endogenous neovascularization induced by AMD-3100 may be a result of the increase in both the area and number of vessels, as well as paracrine augmentation of the expression of VEGF and EPCs. However, the presence of a tissue expander under the flap could block the neovascularization between the flap and the recipient regardless of AMD-3100 treatment and expansion.