Guidelines for the Use of Botulinum Toxin in Otolaryngology From the Korean Society of Laryngology, Phoniatrics and Logopedics Guideline Task Force.

The Korean Society of Laryngology, Phoniatrics and Logopedics created a task force to establish clinical practice guidelines for the use of botulinum toxin (BT) in otolaryngology. We selected 10 disease categories: spasmodic dysphonia, essential vocal tremor, vocal fold granuloma, bilateral vocal fold paralysis, Frey's syndrome, sialocele, sialorrhea, cricopharyngeal dysfunction, chronic sialadenitis, and first bite syndrome. To retrieve all relevant papers, we searched the CORE databases with predefined search strategies, including Medline (PubMed), Embase, the Cochrane Library, and KoreaMed. The committee reported 13 final recommendations with detailed evidence profiles. The guidelines are primarily aimed at all clinicians applying BT to the head and neck area. In addition, the guidelines aim to promote an improved understanding of the safe and effective use of BT by policymakers and counselors, as well as in patients scheduled to receive BT injections.

Immediate and Late Effects of Pulse Widths and Cycles on Bipolar, Gated Radiofrequency-Induced Tissue Reactions in in vivo Rat Skin.

Background: Single to multiple pulse packs of bipolar, alternating current radiofrequency (RF) oscillations have been used for various medical purposes using invasive microneedle electrodes. This study was designed to evaluate the effects of pulse widths and cycles of RF pulse packs on immediate and delayed thermal tissue reactions in in vivo rat skin. Methods: RF energy at the frequency of 1 MHz and power of 70 W was delivered at each experimental setting into in vivo rat skin at 1.5-mm microneedle penetration, and then, tissue samples were obtained after 1 h and 3, 7, 14, and 21 days and histologically analyzed. Results: A single-pulse-pack RF treatment generated coagulative necrosis zones in the dermal peri-electrode area and zones of non-necrotic thermal reactions in the dermal inter-electrode area. Multiple pulse-pack, RF-treated rat skin specimens revealed that the number and size of peri-electrode coagulative necrosis were markedly decreased by increasing the number of pulse packs and accordingly decreasing the conduction time of each pulse pack. The microscopic changes in RF-induced non-necrotic thermal reaction in the inter-electrode area were more remarkable in specimens treated with RF of 7 or 10 pulse packs than in specimens treated with RF of 1-4 pulse packs. Conclusion: The gated delivery of multiple RF pulse packs using a bipolar, alternating current, 1-MHz RF system using insulated microneedle electrodes efficiently generates non-necrotic thermal tissue reactions over the upper, mid, and deep dermis and subcutaneous fat in the inter-electrode areas.

Guideline for the Surgical Management of Locally Invasive Differentiated Thyroid Cancer From the Korean Society of Head and Neck Surgery.

The aim of this study was to develop evidence-based recommendations for determining the surgical extent in patients with locally invasive differentiated thyroid cancer (DTC). Locally invasive DTC with gross extrathyroidal extension invading surrounding anatomical structures may lead to several functional deficits and poor oncological outcomes. At present, the optimal extent of surgery in locally invasive DTC remains a matter of debate, and there are no adequate guidelines. On October 8, 2021, four experts searched the PubMed, Embase, and Cochrane Library databases; the identified papers were reviewed by 39 experts in thyroid and head and neck surgery. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the quality of evidence, and to develop and report recommendations. The strength of a recommendation reflects the confidence of a guideline panel that the desirable effects of an intervention outweigh any undesirable effects, across all patients for whom the recommendation is applicable. After completing the draft guidelines, Delphi questionnaires were completed by members of the Korean Society of Head and Neck Surgery. Twenty-seven evidence-based recommendations were made for several factors, including the preoperative workup; surgical extent of thyroidectomy; surgery for cancer invading the strap muscles, recurrent laryngeal nerve, laryngeal framework, trachea, or esophagus; and surgery for patients with central and lateral cervical lymph node involvement. Evidence-based guidelines were devised to help clinicians make safer and more efficient clinical decisions for the optimal surgical treatment of patients with locally invasive DTC.

Cotton Ball Self-Retraction Technique: A Novel Surgical Method Used During Microflap Dissection.

OBJECTIVES/HYPOTHESIS: Microsurgical removal with a microflap technique via direct laryngoscopy is considered the primary treatment option for vocal cysts. However, the microflap technique is technically difficult and challenging. Therefore, we developed the "cotton ball self-retraction" technique to aid in vocal cyst surgery and reduce the cyst rupture incidence. This study aimed to evaluate the efficacy of this technique in microflap dissection for vocal cysts by comparing its treatment outcomes with those of the conventional technique as well as investigate the rate of recurrence using a retrospective chart review. STUDY DESIGN: A retrospective review. METHODS: We reviewed the medical records of 169 patients who underwent surgery with the microflap technique for vocal cysts from December 2006 to December 2017. The patients were divided into two groups: 78 patients underwent laryngomicrosurgery using the conventional microflap technique (group A), whereas the remaining 91 patients underwent surgery with the microflap technique with cotton ball self-retraction (group B). The voice outcomes and operative data of the two groups were retrospectively reviewed and compared. RESULTS: The cyst ruptured intraoperatively in 42 of 78 (53.8%) patients in group A and 17 of 91 (18.6%) patients in group B. Recurrence during the follow-up period was detected in 9 of 78 (11.5%) patients in group A and 2 of 91 (2.19%) patients in group B. The degrees of improvement in assessed voice parameters were not significantly different between the groups. CONCLUSION: The cotton ball technique allows accurate and effective dissection during microflap surgery for intracordal cysts. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:E2553-E2557, 2021.

Effect of human acellular dermal matrix (Megaderm™) on infra-auricular depressed deformities, Frey's syndrome, and first bite syndrome following parotidectomy: a multi-center prospective study.

BACKGROUND: Parotidectomy is the primary treatment for parotid gland tumors. However, complications may include a prominent facial scar or infra-auricular depressed deformity, Frey's syndrome, first bite syndrome, or other facial pain, numbness, and paralysis. Acellular dermal matrix (ADM) has been widely used to prevent these complications in parotid surgery, but there have been no prospective, multi-center trials documenting its efficacy. This study evaluates the effectiveness of ADM implantation in preventing infra-auricular depressed deformity, Frey's syndrome and first bite syndrome after parotidectomy. METHODS: We analyzed 51 cases of standard parotidectomy and 58 cases of parotidectomy with implantation of Megaderm™ ADM through prospective multicenter trial. Acute complications including infection, seroma, hematoma, skin necrosis, and acute parotid area pain were evaluated 1 week postoperatively. Clinician grading of Frey's syndrome and blinded clinician evaluation of infra-auricular depressed deformities were conducted at 3, 6, and 12 months. Patients evaluated subjective satisfaction with neck appearance, Frey's syndrome quality, and acute parotid area pain at 3, 6, and 12 months. RESULTS: There was a higher incidence of seroma in the Megaderm™ group than in the control group at week 1. The incidence and total clinician-evaluated Frey's syndrome scores were significantly lower in the Megaderm™ group than in the control group at 3, 6, and 12 months. Both the objective and subjective evaluations of the facial contour showed a better outcome in the Megaderm™ group compared to the control group at 3, 6, and 12 months. There were no significant differences between the groups in the patient-reported Frey's syndrome quality scores at 3, 6, and 12 months, but the Megaderm™ group reported significantly less acute pain than the control group. CONCLUSIONS: ADM implantation can effectively reduce the occurrence of Frey's syndrome, infra-auricular depressed deformity, and first bite syndrome after parotidectomy. ADM may be especially advantageous in complex parotidectomy cases when significant complications are expected.

Regenerative efficacy of fibroblast growth factor for the treatment of aged vocal fold: From animal model to clinical application.

OBJECTIVES: We assessed fibroblast growth factor (FGF) regenerative efficacy in an aged vocal fold rat model and confirmed it in a prospective clinical trial. DESIGN, SETTING, AND PARTICIPANTS: For animal experiments, 48 Sprague-Dawley rats were divided into two groups: 24 six-month-olds (young group) and 24 twenty-four-month-olds (old group). FGF was injected once a week thrice into the left vocal fold of the old group, dividing them into two sub-groups (injected [left] and uninjected [right]). Additionally, we conducted a prospective clinical trial for 38 patients with aged atrophic vocal fold. MAIN OUTCOME MEASURES: A month post-injection, excised larynx from the three groups was subjected to comparative histopathological (ratio of relative lamina propria to total vocal fold) and mRNA expression analysis (of procollagen I, hyaluronic acid synthase (HAS)-2 and matrix metalloproteinase (MMP)-2) by real-time PCR. We performed perceptual, stroboscopic, acoustic aerodynamic test and Voice Handicap Index survey prior to and 1, 6 and 12 months after FGF injection. RESULTS: In rats, the relative lamina propria ratio increased after FGF injection. Procollagen I mRNA level decreased, whereas that of HAS-2 and MMP-2 increased significantly in the injected compared to the uninjected old group. Enrolled patients showed improved subjective and objective voice parameters after FGF injection, and these were maintained for a year. Potential side effects were not observed. CONCLUSIONS: Animal experiments and prospective clinical trial suggest that FGF injection to vocal fold can significantly improve voice quality until one year, without complications, and is effective for aged atrophic vocal fold treatment.

Externally Monitored Versus Conventional Buried Flaps in Laryngopharyngeal Reconstruction.

OBJECTIVES: To compare the surgical outcomes of externally monitored and conventional buried flaps with the goal of determining the usefulness of external monitoring of buried flaps. METHODS: In this case-control study with propensity score matching, 30 patients were evenly divided into externally monitored buried flap and conventional buried flap groups. The total operative time for free flap reconstruction, the flap survival rate, the length of hospital stay, the initial time of a reliable visual assessment, complications, the final diet achieved, and the duration until diet initiation were compared between the groups. RESULTS: The mean operative time for reconstruction was 115 minutes (interquartile range, 85-150 minutes) and 142 minutes (interquartile range, 95-180 minutes) in the externally monitored and conventional groups, respectively (P= 0.245). The median length of hospital stay was 24 days (interquartile range, 18-30 days) and 27 days (interquartile range, 20-41 days) in the externally monitored and conventional groups, respectively (P=0.298). The median duration until diet initiation was 15 days (interquartile range, 15-21 days) and 18 days (interquartile range, 15-34 days) in the externally monitored and conventional groups, respectively (P=0.466). The final diet, initial time of a reliable visual assessment, and complications were comparable between the groups, but the external skin paddle provided an excellent visual assessment immediately postoperatively in all cases. CONCLUSION: The outcomes were comparable between the groups, indicating that externalization of the cutaneous component of a buried flap may be a straightforward and useful technique for monitoring a buried anterolateral thigh free flap in laryngopharyngeal reconstructions. The salvage and false-positive rates of compromised flaps should be compared in large subject groups in future studies to prove that the use of an external skin paddle improves flap monitoring.

Traction force microscopy for understanding cellular mechanotransduction.

Under physiological and pathological conditions, mechanical forces generated from cells themselves or transmitted from extracellular matrix (ECM) through focal adhesions (FAs) and adherens junctions (AJs) are known to play a significant role in regulating various cell behaviors. Substantial progresses have been made in the field of mechanobiology towards novel methods to understand how cells are able to sense and adapt to these mechanical forces over the years. To address these issues, this review will discuss recent advancements of traction force microscopy (TFM), intracellular force microscopy (IFM), and monolayer stress microscopy (MSM) to measure multiple aspects of cellular forces exerted by cells at cell-ECM and cell-cell junctional intracellular interfaces. We will also highlight how these methods can elucidate the roles of mechanical forces at interfaces of cell-cell/cell-ECM in regulating various cellular functions. [BMB Reports 2020; 53(2): 74-81].

A 3D-printed polycaprolactone/ß-tricalcium phosphate mandibular prosthesis: A pilot animal study.

OBJECTIVE: In this study, we assessed the effectiveness of a tonsil-derived mesenchymal stem cell (TMSC)-transplanted polycaprolactone/beta-tricalcium phosphate prosthesis (specifically designed for easier fixing and grafting with a single scaffold) on rabbit mandible osteogenesis. METHODS: The mandibles of 18 rabbits were exposed, and 10 × 8-mm bone defects were made. Two rabbits did not receive implants; four were reconstructed with the scaffold control (SC) (SC group); four were reconstructed with scaffolds soaked in peripheral blood (PB) (PB group); four were reconstructed with TMSC-transplanted scaffolds (TMSC group); and four were reconstructed with differentiated osteocyte-transplanted scaffolds (DOC) (DOC group). Each rabbit was sacrificed 12 weeks after surgery, and the area of new bone formation was investigated by mechanical testing, histology, and micro-computed tomography. RESULTS: More extended and denser new bone masses were observed in the TMSC and DOC groups, although fibrosis and vascular formation levels were similar in all groups, suggesting that the dual-structured scaffold alone provides a good environment for bone attachment and regeneration. The bone volumes of representative scaffolds from the SC, PB, TMSC, and DOC groups were 43.12, 48.35, 53.10, and 57.44% of the total volumes, respectively. CONCLUSION: The design of the scaffold resulted in effective osteogenesis, and TMSCs showed osteogenic potency, indicating that their combination could enable effective bone regeneration. LEVEL OF EVIDENCE: NA Laryngoscope, 130:358-366, 2020.

Effect of F-18 Fluorodeoxyglucose Uptake by Bone Marrow on the Prognosis of Head and Neck Squamous Cell Carcinoma.

The purpose of this study was to assess the relationship between F-18 fluorodeoxyglucose (FDG) uptake in bone marrow (BM) on positron emission tomography/computed tomography (PET/CT) and survival in patients with head and neck squamous cell carcinoma (HNSCC). We retrospectively enrolled 157 HNSCC patients who underwent staging FDG PET/CT and subsequent treatment. On PET/CT, primary tumor metabolic characteristics, mean FDG uptake of BM (BM SUV), and BM-to-liver uptake ratio (BLR) were measured. The prognostic significance of FDG uptake of BM for predicting disease progression-free survival and distant failure-free survival was assessed using a Cox proportional hazards regression model. In univariate analysis for disease progression-free survival, increased BM SUV and BLR were associated with poor survival. In multivariate analysis, BLR (p = 0.044; hazard ratio, 1.96), TNM stage (p = 0.014; hazard ratio, 2.87) and maximum FDG uptake of the primary tumor (p = 0.046; hazard ratio, 2.38) were independently associated with disease progression-free survival. For distant failure-free survival, BLR, TNM stage, tumor size, and metabolic parameters of the primary tumor showed prognostic significance in univariate analysis. However, none of the variables showed significance in multivariate analysis. FDG uptake of BM in HNSCC patients might be a significant predictor for disease progression-free survival. Further studies with large patient population are needed to validate the results.

Visceral adipose tissue volume and CT-attenuation as prognostic factors in patients with head and neck cancer.

BACKGROUND: The aim of this study was to evaluate the relationship of the characteristics of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) to the disease progression-free survival and distant failure-free survival of head and neck squamous cell carcinoma (HNSCC). METHODS: We enrolled 152 HNSCC patients who underwent staging 18 F-fluorodeoxyglucose (FDG) positron emission tomography/CT (PET/CT). Maximum FDG uptake (standardized uptake value [SUV]) and total lesion glycolysis (TLG) of the primary tumor and volume, CT-attenuation (Hounsfield units [HU]), and FDG uptake of SAT and VAT were measured. Survival analysis using Cox proportional hazard modeling was performed to assess the relationship between the adipose tissue parameters of PET/CT and survival. RESULTS: Patients with low VAT volume and high VAT HU had significantly worse progression-free survival and distant failure-free survival than those with high VAT volume and low VAT HU. On multivariate analysis, the volume and HU of VAT were significantly correlated with disease progression-free survival and distant failure-free survival after adjusting for age, sex, body mass index, TNM stage, serum C-reactive protein, maximum SUV, and TLG. CONCLUSION: The volume and CT-attenuation of VAT were significantly correlated with disease progression-free survival and distant failure-free survival in patients with HNSCC.

Analysis of neuromonitoring signal loss during retroauricular versus conventional thyroidectomy.

OBJECTIVE: Loss of signal (LOS) during intraoperative neuromonitoring (IONM) of robotic or endoscopic thyroidectomy via a retroauricular approach (RAT) and during conventional open thyroidectomy (COT) was investigated to compare the risk of recurrent laryngeal nerve (RLN) injury between the two groups. STUDY DESIGN: Original article. METHODS: This is a retrospective case series study performed between May 2014 and September 2016. IONM using the NIM 3.0 system (Medtronic Xomed, Inc., Jacksonville, FL) was used for this study. Pre- and postoperative vocal cord functions were assessed using a flexible laryngoscope. LOS types noted intraoperatively and their associations with postoperative vocal cord palsy (VCP) were evaluated. LOS rate and temporary and permanent VCP rates were compared between the two groups. The surgical events associated with LOS were also documented and analyzed in this study. RESULTS: In total, 153 patients were recruited, and 111 patients were enrolled in the RAT group; the remaining 42 patients were enrolled in the COT group. No statistically significant differences in intraoperative LOS (P = 0.812) and postoperative VCP rates (early, permanent; P = 0.259 and P = 0.577, respectively) between the two groups were observed. IONM accuracy of predicting postoperative VCP was 99.1% in our case series. CONCLUSION: On the basis of IONM findings, the risks of injury to RLN were similar between the two groups. Comparison of LOS was an objective method for verifying the novel RAT approach. We applied our IONM protocol and troubleshooting algorithm during RAT with acceptable accuracy, but the international standardized method of IONM is applicable and recommended for reducing false results using vagal nerve stimulation. LEVEL OF EVIDENCE: 3b Laryngoscope, 129:2199-2204, 2019.

Fibroblast growth factor receptor 3-mediated reactivation of ERK signaling promotes head and neck squamous cancer cell insensitivity to MEK inhibition.

Recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) has been a longstanding challenge for head and neck oncologists, and current treatments still have limited efficacy. ERK is aberrantly overexpressed and activated in HNSCC. Herein, we aimed to investigate the cause of the limited therapeutic effect of selumetinib, a selective inhibitor of MEK in HNSCC, as MEK/ERK reactivation inevitably occurs. We assessed the effects of combining selumetinib with fibroblast growth factor receptor 3 (FGFR3) inhibitor (PD173074) on tumor growth. Selumetinib transiently inhibited MAPK signaling and reactivated ERK signaling in HNSCC cells. Rebound in the ERK and Akt pathways in HNSCC cells was accompanied by increased FGFR3 signaling after selumetinib treatment. Feedback activation of FGFR3 was a result of autocrine secretion of the FGF2 ligand. The FGFR3 inhibitor PD173074 prevented MAPK rebound and sensitized the response of HNSCC cells to selumetinib. These results provided rational therapeutic strategies for clinical studies of this subtype of patients that show a poor prognosis with selumetinib. Our data provide a rationale for combining a MEK inhibitor with inhibitors of feedback activation of FGFR3 signaling in HNSCC cells. ERK rebound as a result of the upregulation of FGFR3 and the ligand FGF2 diminished the antitumor effects of selumetinib, which was overcome by combination treatment with the FGFR3 inhibitor.

A clinical prediction score to determine surgical drainage of deep neck infection: A retrospective case-control study.

BACKGROUND: The objective of this retrospective study was to identify predictors of an abscess guaranteed to be surgically drained successfully in patients with deep neck infection (DNI). MATERIALS AND METHODS: We divided 97 consecutive patients with DNI into a drained group and a non-drained group. We then developed a clinical prediction score and validated it in 32 further patients. RESULTS: Significant predictors of successful surgical drainage (i.e., positive for pus) were rim enhancement on computed tomography, C-reactive protein, erythrocyte sedimentation rate, and the neutrophil to lymphocyte ratio. The estimated cut-off values (excluding rim enhancement, which is a yes/no parameter) were 41.25, 56.5, and 8.02, respectively, and the clinical prediction score for each of the four other factors was determined to be 2, 2, 3, and 3 points, respectively. The cut-off score for the sum of these points was 6.5 and the scoring system had an accuracy of 87.5% in the validation group. CONCLUSION: Our clinical prediction scoring system can predict whether drainage is successful in patients with DNI.

Korean survey data reveals an association of chronic laryngitis with tinnitus in men.

The association between chronic laryngitis and tinnitus is not a well-studied topic, unlike the association of these two conditions with many other disorders. Cross-sectional data of 11,347 adults (males: 4,934; females: 6,413), who completed the Korea National Health and Nutrition Examination Survey (KNHANES) from 2010 to 2012 were used to investigate this association. Lifestyle patterns, including smoking and alcohol habits, regular exercise, physical and mental health status, socioeconomic status, nutritional status, and other chronic diseases, were analyzed. Chronic laryngitis and tinnitus were diagnosed by field survey teams, which included otolaryngologists, who conducted chronic disease surveillance using a health status interview, a nutritional status questionnaire, and a physical examination. Chronic laryngitis was significantly associated with age, education beyond high school, depressed mood, voice change, metabolic syndrome, and tinnitus in men. In women, chronic laryngitis was associated with body mass index and diabetes mellitus. Chronic laryngitis in men was significantly associated with tinnitus (odds ratio 1.671, [95% confidence interval: 1.167-2.393]) after adjusting for age, body mass index, smoking status, alcohol intake, regular exercise, metabolic syndrome, education beyond high school, and depressed mood. Additionally, the prevalence of chronic laryngitis increased with increasing severity of tinnitus in men alone (P = 0.002). The study revealed a significant association between chronic laryngitis and tinnitus.

Tracheal reconstruction with a free vascularized myofascial flap: preclinical investigation in a porcine model to human clinical application.

Although there are various methods for tracheal reconstruction, such as a simple approximation with suturing and coverage with adjacent soft tissue or muscle, large defects >50% of the tracheal length still present a clinical challenge. Tissue engineering, a recent promising way to possibly resolve this problem, requires a long preparatory period for stem cell seeding on a scaffold and relatively invasive procedures for stem cell harvesting. As an alternative, we used a vascularized myofascial flap for tracheal reconstruction. In four porcine models, the deep inferior epigastric perforator (DIEP) was used in two and the superior epigastric artery perforator (SEAP) in two. Transformation of the surface of the transplanted myofascial flap was analyzed in the airway environment. The flaps failed in the DIEP group due to venous congestion. At 12 weeks postoperatively, none of SEAP group showed any signs of respiratory distress; the inner surface of the implant exhibited stratified squamous epithelium with sparse cilia. In the clinical setting, a patient who underwent a tracheal reconstruction with a vascularized myofascial flap and 2-year follow-up was in good health with no respiratory distress symptoms.

Detection of peritonsillar abscess using smartphone-based thermal imaging.

OBJECTIVE: Smartphone-based thermal imaging was evaluated for its utility in the detection of peritonsillar abscesses. METHODS: We describe six cases of peritonsillar abscess in which computed tomography and thermography scans of the neck were performed prior to surgery. RESULTS: Open-mouth thermal photographic images were obtained preoperatively from patients, and asymmetric hot spots with significantly higher temperatures in the peritonsillar area were identified as abscesses. CONCLUSIONS: This new portable smartphone-based thermal imaging technique may be useful in the detection of peritonsillar abscesses.

Solute carrier organic anion transporter family member 4A1 (SLCO4A1) as a prognosis marker of colorectal cancer.

PURPOSE: Solute carrier organic anion transporter family member 4A1 (SLCO4A1) is involved in the transport of various compounds, including sugars, bile salts, organic acids, metal ions, amine compounds, and estrogen. SLCO4A1 is highly expressed in several cancers and a gender bias has been observed in colorectal cancer (CRC). We investigated SLCO4A1 expression, its prognostic value in patients with CRC, and its role in CRC cell proliferation and metastasis. METHODS: SLCO4A1 expression was assessed by immunohistochemistry (IHC) on specimens from 84 patients with CRC. The association of SLCO4A1 expression with clinicopathological features was examined. To confirm the biological role of SLCO4A1 in CRC, four CRC cell lines expressing SLCO4A1 were used and SLCO4A1 expression was knocked down by siRNA. Cell proliferation, MTT, migration, invasion, and semisolid agar colony formation assays were performed. RESULTS: SLCO4A1 was overexpressed in 32% of the CRC samples. SLCO4A1 overexpression and pathologic T stage were independent prognostic factors of decreased survival (P = 0.021). Kaplan-Meier analysis indicated a decreased cumulative survival for patients highly expressing SLCO4A1 compared to patients showing low SLCO4A1 expression (Log-rank test, P = 0.025). In cell lines, SLCO4A1 knockdown resulted in a significant decrease of viability, invasion, and migration when compared to control cells. Semisolid colony formation assay indicated that SLCO4A1-knocked down cells presented poor carcinogenic abilities compared to control cells. CONCLUSIONS: SLCO4A1 may be a valuable marker of poor prognostic for CRC. Furthermore, SLCO4A1 plays an important role in CRC cell proliferation, migration, invasion, and carcinogenesis.

The Efficacy of Fibroblast Growth Factor for the Treatment of Chronic Vocal Fold Scarring: From Animal Model to Clinical Application.

OBJECTIVES: This study assessed the regenerative efficacy of basic fibroblast growth factor (FGF) in a rabbit model of chronic vocal fold scarring and then confirmed its utility and safety in a prospective trial of patients with this condition. METHODS: FGF was injected three times, at 1-week intervals, into a chronic vocal fold scar created in a rabbit model. After 1 month, mRNA level of procollagen I, hyaluronic acid synthetase 2 (HAS 2), and matrix metalloproteinase 2 (MMP 2) were analyzed by real-time polymerase chain reaction. The relative densities of hyaluronic acid (HA) and collagen were examined 3 months post-injection. From April 2012 to September 2014, a prospective clinical trial was conducted at a tertiary hospital in Korea. FGF was injected into the mild vocal fold scar of 17 consecutive patients with a small glottic gap. The patients underwent perceptual, stroboscopic, acoustic aerodynamic test, and Voice Handicap Index (VHI) survey prior to and 3, 6, and 12 months after FGF injection. RESULTS: FGF injection of the vocal fold scar decreased the density of collagen and increased mRNA level of HAS 2 and MMP 2 expression significantly compared to the control group injected with phosphate buffered solution in a rabbit model (P<0.05). In the clinical trial, significant improvements in the majority of the subjective and objective voice parameters were registered 3 months after FGF injection and were maintained at 12 months. Complications associated with the FGF injections, such as granuloma, were not observed during the follow-up period. CONCLUSION: Based on the animal model and the prospective clinical trial, vocal fold injections of FGF in patients with mild chronic vocal fold scarring can significantly improve voice quality for as long as 1 year and without side effects. Our results recommend the use of FGF vocal fold injection as an alternative treatment modality for mild chronic vocal fold scarring.