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Cochlear implantation (CI), a widely employed procedure for individuals with severe hearing loss, can encounter a serious complication in the form of implant exposure. In such instances, surgeons are tasked with deciding between salvage measures or opting for reimplantation with a healthy tissue covering. This case presented a challenge with delayed flap necrosis triggered by an increase in the magnetic force of the external device. Notably, this complication manifested 8 years after the initial operation. Following the removal of the device, it was reconstructed successfully using a superficial temporal fascia V-Y advancement flap., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by Mutaz B. Habal, MD.)

Malignant transformation of chronic burn scars are usually toward cutaneous lineages, including squamous cell carcinoma, basal cell carcinoma, and malignant melanoma. Sarcomas are less common. Undifferentiated pleomorphic sarcoma(UPS) is a subtype of soft tissue sarcoma with storiform-pleomorphic cells of uncertain origin, and has sparingly been reported to arise from burn scars. The majority are localized lesions probably due to the spatial distance of mesenchymal cells from the epithelium. The authors describe a rare case of UPS of the chronic burn scar of his knee with ipsilateral femoral and external iliac lymph node metastasis., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Dupuytren's disease is a fibroproliferative disease that affects the palmar hand, causing progressive, permanent, and symptomatic flexion contracture of the digits. It is a disorder of polygenetic and multifactorial origin, usually affecting middle-aged males. Dupuytren's disease developing as a result of hand trauma in younger ages is rarely reported. In this case, we present a 14-year-old male patient with Dupuytren's disease following acute traumatic injury. We performed the fasciectomy and Z-plasty with full thickness skin graft. He recovered completely additional injection of triamcinolone for one year.

Objectives: The mitochondrial ribosomal protein L14 (MRPL14) is encoded by a nuclear gene and participates in mitochondrial protein translation. In this study, we aimed to investigate the role of MRPL14 in thyroid cancer., Methods: We investigated the association between MRPL14 expression and clinicopathological features using The Cancer Genome Atlas (TCGA) and Chungnam National University Hospital (CNUH) databases. Functional studies of MRPL14, including proliferation, migration, invasion, mitochondrial oxidative phosphorylation and reactive oxygen species (ROS) production, were performed in papillary thyroid cancer (PTC) cell lines (B-CPAP and KTC-1)., Results: Based on the TCGA dataset, PTC tissues lost mitochondrial integrity and showed dysregulated expression of overall mitoribosomal proteins (MRPs) compared with normal thyroid tissues. Of 78 MRPs, MRPL14 was highly expressed in thyroid cancer tissues. MRPL14 overexpression was significantly associated with advanced tumor stage, extrathyroidal extension, and lymph node metastasis. MRPL14 increased cell proliferation of thyroid cancer and promoted cell migration via epithelial-mesenchymal transition-related proteins. Moreover, MRPL14 knockdown reduced the expression of oxidative phosphorylation complex IV (MTCO1) and increased the accumulation of ROS. Cotreatment with a ROS scavenger restored cell proliferation and migration, which had been reduced by MRPL14 knockdown, implying that ROS functions as a key regulator of the oncogenic effects of MRPL14 in thyroid cancer cells., Conclusion: Our findings indicate that MRPL14 may promote cell growth, migration, and invasion by modulating ROS in thyroid cancer cells.

Lipoma is a very common benign tumor that occurs in areas of adipose tissue and is commonly found on the whole body, although its occurrence in the hand and finger is rare. Giant lipoma, defined as over 5 cm long in diameter, is a rare benign tumor of abundant soft tissue in the finger. A 24-year-old male patient presented with a giant lipoma on the volar aspect of the index finger of his right hand. Magnetic resonance imaging (MRI) showed an encased multilobulated mass that measured 7.1x1.2x2.3 cm, and histopathological examination revealed lipoma without malignant transformation. Surgical resection of the tumor with a longitudinal and zig-zag incision of the palm was performed exposing the mass surrounding the palmar digital branch of the median nerve. The mass was completely removed, and neurorrhaphy was performed via the microscope to repair the damaged neurovascular bundle. At four months of postoperative follow-up, the patient was completely recovered with no finger paresthesia or limitation of range of motion. As a professional swimmer, the patient has experienced no subsequent difficulty in swimming due to his finger.

Background and Objectives: The expedient resolution of postoperative soft tissue edema is particularly important in hand surgery. Prolonged edema and pain become an obstacle to postoperative rehabilitation, delay return to daily life, and in severe cases, lead to a permanent decrease in range of motion. Based on the common physiology between postoperative hand swelling and complex regional pain syndrome (CRPS), we sought to determine if postoperative mannitol and steroid administration to multiple metacarpal bone fracture patients effectively reduces hand swelling and pain and is beneficial for hand rehabilitation. Materials and Methods: From March 2015 to February 2019, 21 patients who received closed pinning for multiple metacarpal fractures were included in a retrospective cohort study. The control group ( n = 11) underwent a routine recovery, while the treatment group ( n = 10) received dexamethasone and mannitol injections for five days postoperatively. Serial changes in the degree of pain and fingertip-to-palm distance (FPD) were measured in both groups. The duration from surgery to the initiation of rehabilitation and time to full grip was also compared. Results: Compared to the control, the treatment group showed a faster alleviation of pain scores from the postoperative fifth day (2.91 versus 1.80, p = 0.013), and faster recovery of FPD from postoperative two weeks (3.27 versus 1.90, p = 0.002). Time to physical therapy initiation (6.73 versus 3.80 days, p = 0.002) and full grip achievement (42.46 versus 32.70 days, p = 0.002) were also faster in the treatment group. Conclusions: The steroid-mannitol combination treatment for multiple metacarpal bone fracture patients in the acute postoperative phase promoted the reduction of hand edema and pain, leading to the earlier initiation of physical therapy, rapid improvement in joint motion, and faster achievement of full grip.

Oral squamous cell carcinoma (OSCC) has high recurrence and mortality rates despite advances in diagnosis and treatment. Therefore, it is necessary to identify new biomarkers for early detection, efficient monitoring, and prognosis prediction. Since microRNA (miRNA) is stable and detectable in serum, it has been reported to inform the diagnosis and monitor disease progression through liquid biopsy. In this study, a circulating specific miRNA panel in OSCC patients was developed, and its usefulness as a dynamic monitor was validated. Small RNAs were extracted from the serum of OSCC patients (n = 4) and normal controls (n = 6) and profiled using next-generation sequencing. NGS identified 42 differentially expressed miRNAs (DEmiRNAs) in serum between patients with OSCC and healthy controls, with threefold differences (p < 0.05). Combining the 42 DEmiRNAs and The Cancer Genome Atlas (TCGA) databases OSCC cohort, 9 overlapping DEmiRNAs were screened out. Finally, 4 significantly up-regulated miRNAs (miR-92a-3p, miR-92b-3p, miR-320c and miR-629-5p) were identified from OSCC patients via validation in the Chungnam National University Hospital cohort. Application of the specific miRNA panel for distinguishing OSCC patients from healthy controls produced specificity and sensitivity of 97.8 and 74%, respectively. In addition, the serum levels of these 4 miRNAs significantly decreased after complete surgical resection and increased after recurrence. We suggest that circulating 4-miRNA panel might be promising non-invasive predictors for diagnosing and monitoring the progression of patients with OSCC., (© 2023. The Author(s).)

The dorsal metacarpal artery perforator flap is a flap that rises from the hand dorsum. Owing to its reliability and versatility, this flap is used as a workhorse for finger defect. However, to cover the radial-volar defect of the proximal interphalangeal joint (PIPJ) of the index finger, a longer flap is required than before. Here, we introduce the oblique extended reverse first dorsal metacarpal artery (FDMA) perforator flap to cover the radial-volar aspect defect of the index finger. A 45-year-old man got injured to the radial-volar defect of PIPJ of the left index finger caused by thermal press machine. The wound was 2 × 1 cm in size, and the joint and bone were exposed. We used FDMA perforator from anastomosis with palmar metacarpal artery at metacarpal neck. Since the defect was extended to the volar side, the flap was elevated by oblique extension to the fourth metacarpal base level. The fascia was included to the flap, and the flap was rotated counterclockwise. Finally, PIPJ was fully covered by the flap. Donor site was primarily closed. After 12 months of operation, the flap was stable without complication and limitation of range of motion. The oblique extended reverse FDMA perforator flap is a reliable method for covering the radial-volar defect of the PIPJ of the index finger. This flap, which also has an aesthetic advantage, will be a good choice for hand surgeons who want to cover the PIPJ defect of the index finger using a nonmicrosurgical option., Competing Interests: Conflict of Interest None declared., (The Korean Society of Plastic and Reconstructive Surgeons. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Claudin-1 (CLDN1), a major component of tight junction complexes in the epithelium, maintains cellular polarity, and plays a critical role in cell-to-cell communication as well as epithelial cell homeostasis. Although the role of CLDN1 has been widely studied in cancer, its role in the progression and the exact regulatory mechanisms, remain controversial. Using next-generation sequencing, we first analyzed the expression profiles of tumor/non-tumor paired tissue in patients with head and neck squamous cell carcinoma (HNSC) from public and local cohorts and found out that CLDN1 is upregulated in tumors compared to normal tissues. Next, its correlation with lymph node metastasis and poor prognosis was validated in the retrospective cohort, which collectively suggests CLDN1 as an oncogene in HNSC. As expected, the knockdown of CLDN1 inhibited invasive phenotypes by downregulating epithelial-to-mesenchymal transition (EMT) in vitro. To ascertain the regulatory mechanism of CLDN1 in HNSC analysis of GO term enrichment, KEGG pathways, and curated gene sets were used. As a result, CLDN1 was negatively associated with AMP-activated protein kinase (AMPK) and positively associated with transforming growth factor-β (TGF-β) signaling. In vitro mechanistic assay showed that CLDN1 inhibited AMPK phosphorylation by regulating AMPK upstream phosphatases, which led to inhibition of Smad2 activity. Intriguingly, the invasive phenotype of cancer cells increased by CLDN1 overexpression was rescued by AMPK activation, indicating a role of the CLDN1/AMPK/TGF-β/EMT cascade in HNSC. Consistently in vivo, CLDN1 suppression significantly inhibited the tumor growth, with elevated AMPK expression, suggesting the novel observation of oncogenic CLDN1-AMPK signaling in HNSC., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Various enzymes in the one-carbon metabolic pathway are closely related to the development of tumors, and they can all be potential targets for cancer therapy. Serine hydroxymethyltransferase2 ( SHMT2 ), a key metabolic enzyme, is very important for the proliferation and growth of cancer cells. However, the function and mechanism of SHMT2 in head and neck cancer (HNC) are not clear. An analysis of The Cancer Genome Atlas (TCGA) data showed that the expression of SHMT2 was higher in tumor tissue than in normal tissue, and its expression was significantly associated with male sex, aggressive histological grade, lymph node metastasis, distant metastasis, advanced TNM stage, and lymphovascular invasion in HNC. SHMT2 knockdown in FADU and SNU1041 cell lines significantly inhibited cell proliferation, colony formation, migration, and invasion. Additionally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses using TCGA data revealed that SHMT2 was closely related to cancer stem cell regulation and maintenance. Furthermore, we found that silencing SHMT2 inhibited the expression of stemness markers and tumor spheroid formation compared with a control group. On the contrary, stemness markers were significantly increased after SHMT2 overexpression in HEP-2 cells. Interestingly, we found that knocking down SHMT2 reduced the expression of genes related to the Notch and Wnt pathways. Finally, silencing SHMT2 significantly reduced tumor growth and decreased stemness markers in a xenograft model. Taken together, our study suggests that targeting SHMT2 may play an important role in inhibiting HNC progression.

Objectives: This study aimed to investigate the influence of the respective mechanical and chemical pre-treatments on the composite repair of a CAD/CAM hybrid ceramic using a microtensile bond strength test (μTBS)., Methods: 15 CAD/CAM Blocks of Vita Enamic (VE) were randomly sectioned into three mechanical pre-treatments: (1.) Diamond bur (D), (2.) Airborne abrasion (A), (3.) Tribochemical silica coating (T) and subsequently five chemical pre-treatments: (1.) Clearfil SE Bond Bond (B; negative control), (2.) ESPE Sil (S), (3.) Clearfil Ceramic Primer Plus (CPP), (4.) Clearfil Repair (CR) and (5.) Scotchbond Universal (SCB). Per block, n = 20 specimens were sawn. Half of the specimens were randomly selected and subjected to an immediate bond strength test, while the other half was subjected to artificial aging for 6 months 180 days at 37 °C and subsequent thermocycling of 5000 cycles. A μTBS was performed and data (MPa) were compared in one-way and two-way ANOVA and Tukey's HSD. Paired-t-test was used for artificial aging (α = 0.05). Debonded specimens were analyzed of for failure modes with a stereomicroscope (SEM)., Results: The results of one-way ANOVA for the fifteen fastening procedures after aging indicated significant differences according to SCB-A and CPP-T. Two-way ANOVA after aging observed inferior bond strength for SCB. No differences were observed for mechanical pre-treatments. Artificial aging showed a significant reduction in bond strength on most of the fastening procedures., Significance: SCB showed the lowest bond strength values besides B, S, CPP, and CR. MDP and silane are both suitable for the repair of VE., (Copyright © 2022 The Academy of Dental Materials. Published by Elsevier Inc. All rights reserved.)

Objectives: Thyroid cancer is the most common endocrine tumor, with rapidly increasing incidence worldwide. However, its transcriptomic characteristics associated with immunological signatures, driver fusions, and recurrence markers remain unclear. We aimed to investigate the transcriptomic characteristics of advanced papillary thyroid cancer., Methods: This study included 282 papillary thyroid cancer tumor samples and 155 normal samples from Chungnam National University Hospital and Seoul National University Hospital. Transcriptomic quantification was determined by high-throughput RNA sequencing. We investigated the associations of clinical parameters and molecular signatures using RNA sequencing. We validated predictive biomarkers using the Cancer Genome Atlas database., Results: Through a comparison of differentially expressed genes, gene sets, and pathways in papillary thyroid cancer compared to normal tumor-adjacent tissue, we found increased immune signaling associated with cytokines or T cells and decreased thyroid hormone synthetic pathways. In addition, patients with recurrence presented increased CD8+ T-cell and Th1-cell signatures. Interestingly, we found differentially overexpressed genes related to immune-escape signaling such as CTLA4, IDO1, LAG3, and PDCD1 in advanced papillary thyroid cancer with a low thyroid differentiation score. Fusion analysis showed that the PI3K and mitogen-activated protein kinase (MAPK) signaling pathways were regulated differently according to the RET fusion partner genes (CCDC6 or NCOA4). Finally, we identified HOXD9 as a novel molecular biomarker that predicts the recurrence of thyroid cancer in addition to known risk factors (tumor size, lymph node metastasis, and extrathyroidal extension)., Conclusion: We identified a high association with immune-escape signaling in the immune-hot group with aggressive clinical characteristics among Korean thyroid cancer patients. Moreover, RET fusion differentially regulated PI3K and MAPK signaling depending on the partner gene of RET, and HOXD9 was found to be a recurrence marker for advanced papillary thyroid cancer.

Rationale: Tubular apocrine adenoma (TAA) is a very rare benign neoplasm of the apocrine gland. The typical anatomical locations are mostly hair-bearing areas, where normal apocrine glands are abundant., Patient Concerns: We report the case of a 40-year-old patient with a tubular apocrine adenoma on a non-hair-bearing area., Diagnoses: Ultrasonography showed a 0.4-cm-sized hypoechoic nodule in the subcutaneous plane of the left palm at the fourth carpometacarpal joint level., Interventions: Surgical resection was performed and histopathological examination revealed lobules of well-differentiated dilated tubular structures at the dermis level., Outcomes: At 1 year of postoperative follow-up, the patient was completely recovered without signs of recurrence., Lessons: Diagnosis of TAA can be misleading due to its unusual location and inconspicuous appearance. Immunohistochemistry for epithelial membrane antigen and gross cystic disease fluid protein-15 is crucial for the proper diagnosis. Complete excision is recommended to prevent recurrence., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Despite recent advances in understanding the complex immunologic dysfunction in the tumor microenvironment (TME), fewer than 20% of patients with head and neck squamous cell carcinoma (HNSCC) respond to immune checkpoint blockade (ICB). Thus, it is important to understand how inhibitory IC receptors maintain the suppressed dysfunctional TME, and to develop more effective combination immunotherapy. This study evaluated the immune-modulating effects of Curcumin, which has well-established anti-cancer and chemopreventive properties, and its long-term safety as a phytochemical drug., Methods: We carried out the western blot and small interfering RNA (siRNA) transfection assay to evaluate the effects of Curcumin on IC ligands and IC ligands function in HNSCC. Through T-cell cytotoxicity assay and measurements of cytokine secretion, we assessed the effects of combination of Curcumin with programmed death-ligand 1 (PD-L1) Ab on cancer cell killing. Flow cytometry were used to analyze the effects of Curcumin on the expression of programmed cell death protein 1 (PD-1) and T-cell immunoglobulin and mucin-domain3 (TIM-3) on CD4, CD8 and Treg. Immunofluorescence, immunohistochemistry and western blot were used to detecte the cytokine (IFN-γ, Granzyme B), IC receptors (PD-1 and TIM-3) and its ligands (PD-L1, PD-L2, Galectin-9) in xenograft mouse model and 4-nitroquinoline-1-oxide (4-NQO) oral cancer model., Results: We found that Curcumin decreased the expression of IC ligands such as PD-L1, PD-L2, and Galectin-9 in HNSCC, leading to regulation of epithelial-to-mesenchymal transition-associated tumor invasion. Curcumin also effectively restored the ability of CD8 + cytotoxic T cells to lyse cancer cells. To evaluate the effect of Curcumin on the TME further, the 4-NQO oral cancer model was used. Curcumin increased T-cell proliferation, tumor-infiltrating lymphocytes (TILs), and effector cytokines, and decreased the expression of PD-1, TIM-3, suppressive IC receptors and their ligands (PD-L1, PD-L2, and Galectin-9) in the TME, implying reinvigoration of the exhausted CD8 + T cells. In addition, Curcumin inhibited expression of CD4 + CD25 + FoxP3 + Treg cells as well as PD-1 and TIM-3., Conclusions: These results show that Curcumin reinvigorates defective T cells via multiple (PD-1 and TIM-3) and multi-level (IC receptors and its ligands) IC axis suppression, thus providing a rationale to combine Curcumin with conventional targeted therapy or ICB as a multi-faceted approach for treating patients with HNSCC., (Copyright © 2021. Published by Elsevier GmbH.)

Growth and differentiation factor 15 (GDF15), a divergent member of the transforming growth factor-β (TGF-β) superfamily, has been reported to be overexpressed in different kinds of cancer types. However, the function and mechanism of GDF15 in head and neck cancer (HNC) remains unclear. The Cancer Genome Atlas (TCGA) data show that the expression of GDF15 is significantly associated with tumor AJCC stage, lymph vascular invasion and tumor grade in HNC. In this study, we confirmed that knockdown of GDF15 attenuated: cell proliferation, migration and invasion via regulation of EMT through a canonical pathway; SMAD2/3 and noncanonical pathways; PI3K/AKT and MEK/ERK in HNC cell lines. Furthermore, we found that early growth response 1 (EGR1) was a transcription factor of GDF15. Interestingly, we also demonstrated that GDF15 could regulate the expression of EGR1, which meant a positive feedback loop occurred between these two factors. Moreover, combined inhibition of both GDF15 and EGR1 in a HNC mouse xenograft model showed significantly decreased tumor volume compared to inhibition of EGR1 or GDF15 alone. Our study showed that the GDF15-EGR1 signaling axis may be a good target in HNC patients.

Despite considerable advances, studying electrocommunication of weakly electric fish, particularly in pulse-type species, is challenging as very short signal epochs at variable intervals from a few hertz up to more than 100 Hz need to be assigned to individuals. In this study, we show that supervised learning approaches offer a promising tool to automate or semiautomate the workflow, and thereby allowing the analysis of much longer episodes of behavior in a reasonable amount of time. We provide a detailed workflow mainly based on open resource software. We demonstrate the usefulness by applying the approach to the analysis of dyadic interactions of Gnathonemus petersii . Coupling of the proposed methods with a boundary element modeling approach, we are thereby able to model the information gained and provided during agonistic encounters. The data indicate that the passive electrosensory input, in particular, provides sufficient information to localize a contender during the pre-contest phase, fish did not use or rely on the theoretically also available sensory information of the contest outcome-determining size difference between contenders before engaging in agonistic behavior., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Pedraja, Herzog, Engelmann and Jung.)

Mitochondrial targeted therapy is a next-generation therapeutic approach for cancer that is refractory to conventional treatments. Mitochondrial damage caused by the excessive accumulation of reactive oxygen species (ROS) is a principle of mitochondrial targeted therapy. ROS in nonthermal plasma-activated media (NTPAM) are known to mediate anticancer effects in various cancers including head and neck cancer (HNC). However, the signaling mechanism of HNC cell death via NTPAM-induced ROS has not been fully elucidated. This study evaluated the anticancer effects of NTPAM in HNC and investigated the mechanism using transcriptomic analysis. The viability of HNC cells decreased after NTPAM treatment due to enhanced apoptosis. A human fibroblast cell line and three HNC cell lines were profiled by RNA sequencing. In total, 1 610 differentially expressed genes were identified. Pathway analysis showed that activating transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP) were upstream regulators. Mitochondrial damage was induced by NTPAM, which was associated with enhancements of mitochondrial ROS (mtROS) and ATF4/CHOP regulation. These results suggest that NTPAM induces HNC cell death through the upregulation of ATF4/CHOP activity by damaging mitochondria via excessive mtROS accumulation, similar to mitochondrial targeted therapy., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2021 Chan Oh et al.)

Background: Reconstruction of perineal defect is challenging. The goal of reconstruction is to maintain normal function with good esthetic outcomes. Coverage of the perineal defect is often difficult with one loco-regional flap when the size of defect is very extensive. In this article, clinical applications of the propeller posteromedial thigh perforator (PMTP) flap for extensive perineal defects were described., Patients and Methods: Eight patients underwent perineal reconstruction with propeller PMTP flaps from March 2013 to December 2018. The average age of the patients was 65 years (range: 52-80 years). The causes of the defects included infection and skin cancers. The perforator was a branch of deep femoral artery. The flap was harvested as a perforator-based flap and rotated 180° to the defect area (propeller flap design)., Results: The average flap size was 256.5 cm 2 (range: 136-400 cm 2 ) and average follow-up period was 22.4 months (range: 6-48 months). All flaps survived after surgery without major complications. The donor sites were all primarily closed and the patients were all satisfied during the follow-up period., Conclusion: The propeller PMTP flap is an adequate new option for reconstructing extensive perineal defects. The flap avoids the need for microanastomosis and replaces the defect with similar tissue., (© 2021 Wiley Periodicals LLC.)

Background: Mitochondrial stress is known to activate the mitochondrial unfolded protein response (UPR mt ). The UPR mt results in the secretion of mitochondrial cytokines (mitokines), which can promote a hormetic response cell nonautonomously, and has been reported to be protumorigenic. Growth differentiation factor 15 (GDF15) is a well-characterized mitokine, which is reported to have a mitohormetic effect. Thus, we investigated whether GDF15 induction could prime a subpopulation of thyroid cancer cells to provide invasive advantages. Methods: The UPR mt , including mitokine expression, was assessed in the context of thyroid cancer in vitro and in vivo . GDF15 expression in 266 patients with papillary thyroid carcinoma (PTC) was determined by immunohistochemistry. The serum levels of GDF15 were measured in healthy subjects and PTC patients. In addition, our own and The Cancer Genome Atlas data were analyzed to determine the expression level of GDF15 in thyroid cancers. The role of GDF15 in tumor aggressiveness was investigated by observing the effects of GDF15 knockdown in BCPAP, TPC-1, 8505C, and FRO cells. Results: Pharmacological inhibition of mitochondrial oxidative phosphorylation function in thyroid cancer cells robustly increased GDF15 expression. The expression of GDF15 was associated with activation of the mitochondrial integrated stress response pathway in PTC patients. Circulating GDF15 levels were significantly higher in PTC patients than in the controls, and tumor expression of GDF15 was related to tumor aggressiveness. In vitro and in vivo knockdown of GDF15 in a thyroid cancer model showed decreased viability, migration, and invasion compared with the control cells via regulation of STAT3. Conclusions: In this study, we demonstrated that GDF15 is a mitokine induced in thyroid cancer cells upon mitochondrial stress. GDF15-induced STAT3 activation determined tumor progression in thyroid cancer. The GDF15-STAT3 signaling axis may be a target in aggressiveness of thyroid cancer.

(1) Background: Nonthermal plasma (NTP) induces cell death in various types of cancer cells, providing a promising alternative treatment strategy. Although recent studies have identified new mechanisms of NTP in several cancers, the molecular mechanisms underlying its therapeutic effect on thyroid cancer (THCA) have not been elucidated. (2) Methods: To investigate the mechanism of NTP-induced cell death, THCA cell lines were treated with NTP-activated medium -(NTPAM), and gene expression profiles were evaluated using RNA sequencing. (3) Results: NTPAM upregulated the gene expression of early growth response 1 ( EGR1 ). NTPAM-induced THCA cell death was enhanced by EGR1 overexpression, whereas EGR1 small interfering RNA had the opposite effect. NTPAM-derived reactive oxygen species (ROS) affected EGR1 expression and apoptotic cell death in THCA. NTPAM also induced the gene expression of growth arrest and regulation of DNA damage-inducible 45α ( GADD45A ) gene, and EGR1 regulated GADD45A through direct binding to its promoter. In xenograft in vivo tumor models, NTPAM inhibited tumor progression of THCA by increasing EGR1 levels. (4) Conclusions: Our findings suggest that NTPAM induces apoptotic cell death in THCA through a novel mechanism by which NTPAM-induced ROS activates EGR1/GADD45α signaling. Furthermore, our data provide evidence that the regulation of the EGR1/GADD45α axis can be a novel strategy for the treatment of THCA.

Particulate matter (PM) is an environmental exposure factor that adversely affects human health. PM is a risk factor for various diseases. However, the mechanism by which PM affects the vocal folds (VF) has not yet been evaluated. Thus, we investigated the cytotoxic effects of PM on human vocal fold fibroblasts (hVFF) and the underlying signaling pathways. hVFF were isolated from human VF. The effect of PM on hVFF, and the underlying mechanism, were analyzed using Western blot, quantitative real-time polymerase chain reaction, and flow cytometry. In addition, a histological evaluation was performed in animal experiments. Cell proliferation decreased after the PM treatment. PM increased the expression of interleukin (IL)-6 and IL-1β. The generation of reactive oxygen species (ROS) in PM-treated hVFF and subsequent activation of the mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) pathways were confirmed. Furthermore, PM increased the expression of fibrosis-related markers and induced the accumulation of collagen in the extracellular matrix. As a result, PM exposure significantly enhances the inflammatory response on VF through the ROS-mediated activation of the MAPK and NF-κB signaling pathways. In addition, PM promotes differentiation into myofibroblasts and induces fibrosis. These results suggest that PM triggers an inflammatory reaction through ROS production and causes VF fibrosis.

Background: Brn3a/Pou4f1 is a class IV POU domain-containing transcription factor and has been found to be expressed in a variety of cancers. However, the mechanism and action of Brn3a in thyroid cancer has not been investigated., Purpose: To investigate the role of Brn3a in thyroid cancer progression and its clinical implication., Methods: We examined Brn3a expression status in patients with thyroid cancer and analyzed relationships between Brn3a expression and clinicopathological findings using The Cancer Genome Atlas (TCGA) database. For functional in vitro analysis, proliferation, migration, invasion assay, and Western blotting were performed after overexpression or suppression of Brn3a., Results: The promoter hypermethylation of Brn3a was found in patients with aggressive thyroid cancer and Brn3a was downregulated in tissues of patients with thyroid cancer. In TCGA database, the low-Brn3a-expression group revealed a more aggressive phenotype, including T stage and extrathyroid extension when compared with the high-Brn3a-expression group. Overexpression of Brn3a suppressed cell migration and invasion via regulation of epithelial-mesenchymal transition (EMT)-associated proteins in thyroid cancer cell lines. Brn3a overexpression also downregulated signal transducer and activator of transcription 3 (STAT3) signaling through suppression of tyrosine-protein kinase Met (c-MET). In contrast, knockdown of Brn3a by small interfering ribonucleic acid (siRNA) significantly increased cell migration and invasion through upregulation of c-MET/STAT3. These results imply that Brn3a suppresses tumor metastasis via c-MET/STAT3 inhibition and EMT suppression in thyroid cancer., Conclusions: Our findings show that Brn3a is a potential tumor suppressor that leads to reduced cancer cell migration and invasion in thyroid cancer. Elucidation of the Brn3a-regulated cancer pathways may therefore provide novel therapeutic strategies to control thyroid cancer metastasis., (© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Identification of therapeutic targets in head and neck squamous cell carcinoma (HNSCC) is essential because most of the patients with advanced HNSCC have a poor prognosis. Homeobox genes constitute a large cluster of transcription factors with important regulatory roles in mammalian embryonic development and cell differentiation. The oncogenic role of homeobox B5 (HOXB5) in HNSCC has not been investigated., Materials and Methods: We used The Cancer Genome Atlas (TCGA) data to evaluate the correlations between HOXB5 expression and various HNSCC clinicopathological factors. We knocked down HOXB5 expression in HNSCC cell lines and explored the in vitro and in vivo effects on cell proliferation and motility, and HOXB5 signaling., Results: The Cancer Genome Atlas (TCGA) data shows that HOXB5 is overexpressed in HNSCC compared to normal tissues and significantly associates with tumor stage (P = 0.003), lymph node metastasis (P = 0.031), disease stage (P = 0.002), and angiolymphatic invasion (P = 0.004). Our results also show that HOXB5 expression is up-regulated in HNSCC cell lines, and HOXB5 knockdown significantly reduced cell proliferation and tumor growth in vitro and in vivo. Inhibition of HOXB5 decreases cell migration and invasion via suppression of epithelial-to-mesenchymal transition (EMT)-associated proteins expression. Moreover, HOXB5 directly binds to the promoter region of EGFR and consequently regulates the activity of the Akt/Wnt/β-catenin signaling axis., Conclusion: HOXB5 may be a novel therapeutic target as an oncogenic driver by regulating EGFR transcription in HNSCC., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2019 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Purpose: We assessed the optimal time for intact parathyroid hormone (iPTH) measurement for early detection of post-total thyroidectomy (TT) hypocalcemia in patients with papillary thyroid carcinoma (PTC)., Methods: In this single-center prospective cohort study, 143 patients who underwent TT with central neck dissection with or without lateral neck dissection for PTC were included. Biochemical profiles including iPTH, corrected total calcium, and ionized calcium within 24 h after surgery were analyzed., Results: The 4-h postoperative iPTH was the most reliable predictor of post-TT transient or permanent hypoparathyroidism (cutoff for hypocalcemia was 3.75 pg/mL, AUC = 0.885, P < 0.001, sensitivity 81.6%, specificity 86.0%; cutoff for permanent hypocalcemia was 2.48 pg/mL, AUC = 0.819, P < 0.001, sensitivity 100%, specificity 57.8% calculated using ROC curves)., Conclusions: The 4-h postoperative iPTH can most accurately predict hypoparathyroidism after TT with central neck dissection to treat PTC and facilitate the early discharge of low-risk postoperative hypoparathyroidism patients and decrease unnecessary overnight observation and calcium supplementation.

Combinations of various treatment modalities were shown to be more effective than monotherapy when treating hypertrophic scars and keloids. This study was conducted to assess the effectiveness of combination therapy with non-ablative fractional laser and intralesional steroid injection. From May 2015 to June 2017, a total of 38 patients with hypertrophic scars or keloids were evaluated. The control group of 21 patients received steroid injection alone, and 17 patients (the combined group) received 1550-nm erbium-glass fractional laser treatment and steroid injection simultaneously. The mean number of treatment sessions was statistically fewer in the combined group than in the control group (6.95 vs 5.47, P = .042). There was a significant difference in the patient's scale in the combined group (14.62 vs 22.82, P = .005); however, the observer's scale was not significantly different (17.92 vs 20.55, P = .549). The recurrence rate was 38.1% (8/21) in the control group and 35.3% (6/17) in the combined groups and showed no significant difference (P = .859). However, the mean remission period was statistically longer in the combined group (3.00 months vs 4.17 months, P = .042). Combination therapy with non-ablative fractional laser and intralesional steroid injection showed better results for the treatment of hypertrophic scars and keloids with fewer treatment sessions, better patient satisfaction, and longer remission periods., (© 2019 Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Fibroblast growth factor 21 (FGF21) plays important roles in regulating glucose, lipid, and energy metabolism; however, its effects in tumors remain poorly understood. To understand the role of FGF21 in regulating tumor aggressiveness in thyroid cancer, serum levels of FGF21 were measured in healthy subjects and patients with papillary thyroid cancer (PTC), and expression levels of FGF21, FGF receptors (FGFRs), and β-klotho (KLB) were investigated in human thyroid tissues. The cell viability, migrating cells, and invading cells were measured in PTC cells after treatment with recombinant FGF21. Higher serum levels of FGF21 were found in patients with thyroid cancer than in control participants, and were significantly associated with body mass index (BMI), fasting glucose levels, triglyceride levels, tumor stage, lymphovascular invasion, and recurrence. Serum FGF21 levels were positively correlated with the BMI in patients with PTC, and significantly associated with recurrence. Recombinant FGF21 led to tumor aggressiveness via activation of the FGFR signaling axis and epithelial-to-mesenchymal transition (EMT) signaling in PTC cells, and AZD4547, an FGFR tyrosine kinase inhibitor, attenuated the effects of FGF21. Hence, FGF21 may be a new biomarker for predicting tumor progression, and targeting FGFR may be a novel therapy for the treatment of obese patients with PTC.

Head and neck cancer often requires multiple defect reconstruction that are too far apart to handle with 1 flap. However, 1 flap with skin graft, or multiple flap reconstruction is always not possible due to recipient site factors and lack of sufficient donor site. In this report, we share our experience on reconstruction of multiple, and distant head and neck defects with 1 large radial forearm flap that was vertically inset to cover multiple defect on face, and then tunneled to reach down to the neck. Due to the longer dimension, this flap could be utilized not only to reconstruct the face and neck area, but also simultaneously reconstruct face and orbit, or face and scalp area. We think that this modification of the radial forearm flap could provide a useful surgical option for multiple and distant head and neck reconstructions.

Background: Parotidectomy is the treatment of choice in many parotid tumors. Due to the extensive nature of the procedure, unfavorable complications such as gustatory sweating, surgical site depression are common. Various techniques using fascia, muscle or AlloDerm have been developed but debate still remains regarding its availability and affordability. We applied a newly developed acellular dermal matrix (Insuregraf) to the parotidectomy field to act as a physical barrier and to provide adequate filling effect for prevention of functional and aesthetic complications., Methods: From March 2010 to March 2017, 30 patients with parotid tumors underwent superficial parotidectomy. Twenty patients underwent only superficial parotidectomy. Ten patients had Insuregraf applied to the surgical site after superficial parotidectomy. We evaluated the incidence of Frey's syndrome, surgical site depression, and patient satisfaction rate in both groups., Results: The incidence of Frey's syndrome was lower in the Insuregraf group (0 vs. 2). Surgical site depression was also lower in the Insuregraf group (2 vs. 20). Satisfaction score for facial contour in Insuregraf group was 9.2 out of 10, which was comparable to 6.2 out of 10 in the control group., Conclusion: Application of Insuregraf after superficial parotidectomy is an effective surgical procedure to prevent complications such as Frey's syndrome and surgical site depression. This technique is affordable and safe with no immune reactions. Above all this surgical method should be considered as an option for patients who are concerned about the contour of the face after surgery.

Trichoepithelioma is a benign tumor which can be easily confused with basal cell carcinoma. Since both tumors are histologically similar, it is important to distinguish them correctly as the courses for treatment are very different. Basal cell carcinoma is malignant; therefore, it requires total surgical excision, including a wide healthy margin. In contrast, trichoepithelioma requires only simple excision. A study involving a 69-year-old woman with a simple mass on the nasal tip was described in this study. On examination, a single skin-colored, round protruding mass (approximately 0.5 × 0.5 cm) was observed. Simple excision was performed and basal cell carcinoma was diagnosed at the initial biopsy. However, clinically, we considered it to be a benign tumor; therefore, we sought a histologic reconfirmation. Consequently, trichoepithelioma was diagnosed on histopathologic examination. When a small, round protruding simple mass is histologically diagnosed to be a basal cell carcinoma, it is important to suspect trichoepithelioma and seek histologic reconfirmation.

Objectives: Laminin subunit beta-3 (LAMB3) is a major component of the basement membrane zone. In our study, we investigated the role of LAMB3 in head and neck squamous cell carcinoma (HNSCC) progression and its clinical implication as a prognostic biomarker., Materials and Methods: A retrospective analysis of 100 patients with HNSCC who had undergone curative surgery from 1999 to 2011 was performed. We evaluated LAMB3 expression by immunohistochemistry and its associations with clinicopathological characteristics and survival. For functional in vitro analyses, cell proliferation, migration, and invasion and western blot assays were performed following LAMB3 suppression. In addition, the role of LAMB3 in cisplatin-induced cytotoxicity was clarified by measuring cell proliferation., Results: LAMB3 expression was up-regulated in HNSCC cell lines and patient tissues. High LAMB3 expression was significantly associated with positive lymph node metastasis (odds ratio: 6.316; P < 0.001) and poor prognosis in patients with HNSCC. LAMB3 suppression reduced cell migration/invasion via down-regulation of epithelial-to-mesenchymal transition-associated proteins (Vimentin and Slug). Moreover, LAMB3 suppression increased cisplatin cytotoxicity in HNSCC cells., Conclusion: Our findings indicate that LAMB3 may be used as a prognostic biomarker in HNSCC and support that LAMB3 silencing could induce the sensitivity of anti-cancer drugs such as cisplatin., (Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Eccrine porocarcinoma is a rare malignant tumor arising from the intraepidermal ductal portion of the eccrine sweat gland. It develops either spontaneously or from a long standing benign eccrine poroma. This entity usually affects older people and is commonly located on the lower extremities, the trunk, and the head. We report a case of eccrine porocarcinoma on the left cheek in an 85-year-old male. In our case, the tumor was treated with wide excision and postoperative adjuvant radiation therapy. The patient recovered well without local recurrence and distant metastasis during the 14-month follow-up period. Wide excision and postoperative adjuvant radiation therapy can be considered as a safe and effective treatment option in treating patients with eccrine porocarcinoma.

Schwannoma is a benign tumor rarely found in the head and neck and much less commonly found in the intraparotid facial nerve. It is a slow-growing encapsulated tumor originating from the Schwann cells or axonal nerve sheath. It can occur anywhere along the course of the facial nerve. Patients may present with symptoms of facial palsy, but the most common presenting symptom is an asymptomatic swelling. Diagnosis is usually difficult before surgical removal and histopathological examination. We report a rare case of intraparotid facial nerve schwannoma in a 57-year-old female who had sustained a mass of the right preauricular area for 3 years. She reported no pain or facial muscle weakness. Enhanced computed tomography findings revealed the impression of pleomorphic adenoma. However, intraoperative gross findings were not characteristic of pleomorphic adenoma, and a frozen biopsy was performed resulting in the impression of a nerve sheath tumor. We performed an extracapsular surgical excision without parotidectomy. Permanent histopathology and immunohistochemistry reports diagnosed the mass as schwannoma. There were no complications including facial palsy after surgery. No recurrence was found at 6 months after surgery.

Replantation using microvascular anastomosis is considered to be the optimal method in treating the amputated ear in terms of resulting color, texture, and shape. Only a few cases of ear replantation have been reported because it is anatomically difficult to identify suitable vessels for anastomosis. We successfully replanted the amputated helical rim of the ear using single arterial anastomosis. A 37-year-old man had his helical rim amputated by a human bite. The amputee was about 4 × 1 cm in dimension, composed of skin and soft tissue including auricular cartilage. Replantation was performed anastomosing a small artery of the amputee with a terminal branch of the posterior auricular artery. After replantation, intravenous heparinization was performed and prostaglandin E1 and aspirin were administered. Venous congestion was decompressed by stab incisions applied with heparin solution soaked gauze. Venous congestion of the amputee slowly began to resolve at 4 days after the operation. The amputated segment of the helical rim survived completely with good aesthetic shape and color. The authors propose that performing microvascular anastomosis should be attempted especially if it is possible to detect vessels on cut surfaces of ear amputee and stump. Proper postoperative care for venous congestion, arterial insufficiency, and infection should be followed for amputee survival.

Lymphatic malformations are benign vascular malformations rarely seen in adults. There have been only around 100 cases reported in the literature, most of them located in the head and neck area. The etiology is poorly understood but trauma, infection, or tumors have been suggested as possible causes. We present an unusual case of lymphatic malformations in the lower extremity of a 56-year-old male patient after minor trauma. The masses were asymptomatic but progressively enlarged for a period of 2 months, developing into a mass with a 21-cm-long axis in computed tomography images. Total surgical resection was performed and there were no complications or recurrence during the 1-year follow-up period. We present this rare case with a review of relevant previous literatures.

Primary malignant lymphoma rarely presents as a mass in the salivary gland. It accounts for about 1% of salivary gland tumors. The lymphomas of the parotid gland are mainly non-Hodgkin's lymphoma of B-cell follicular type. It usually occurs in male adults and is very rare in children. In contrast to the intractable disease course of adult parotid follicular lymphoma, when occurred in children or adolescent, its prognosis is very good when it is first treated with surgical excision. Thus, a solitary follicular lymphoma in an extranodal site that has occurred in children is termed separately as pediatric follicular lymphoma (PFL). We share our treatment experience of a 16-year-old PFL patient through surgical removal combined with superficial parotidectomy. In line with the few previous case reports of PFL, we suggest that active surgical removal should be undertaken for solitary, extranodal follicular lymphoma of the pediatric and adolescent population.

Background: Extrathyroidal extension (ETE) is a risk factor for poor papillary thyroid carcinoma (PTC) outcomes. However, the clinical significance of ETE according to primary tumor size has not been well-established. The purpose of this study was to compare differences in clinical outcomes, according to the presence and extent of ETE, between different primary tumor size groups., Methods: In total, 381 patients with PTC underwent total thyroidectomy with or without lymph node (LN) dissection from 2004 to 2010. We divided the patients into two groups according to primary tumor size: ≤ 1 cm or >1 cm. Each group was further divided into subgroups according to the presence of ETE (ETE vs. no ETE) and degree of ETE (microscopic ETE vs. macroscopic ETE). The clinicopathological features and rate of recurrence during follow-up were compared among groups., Results: Among the PTC patients with primary tumors >1 cm, patients with ETE had a higher recurrence rate than those without ETE, and only macroscopic ETE affected recurrence in patients with PTC > 1 cm (P < 0.05). However, there was no significant difference in recurrence rates between those without ETE and those with microscopic ETE (P = 0.100). When the primary tumor size was less than 1 cm, there were no difference in recurrence rates between the groups with or without ETE, or between the groups with microscopic and macroscopic ETE (P > 0.05)., Conclusions: Our data suggests that the presence and degree of ETE may be associated with PTC outcome based on primary tumor size., (Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Skeletal cavernous hemangiomas are rare, benign tumors that may involve the supraorbital rim and orbital roof. However, such involvement is extremely rare. We report a case of skeletal cavernous hemangioma of the frontal bone involving the orbital roof and rim. En bloc excision and reconstruction, using a calvarial bone graft for the orbital roof and rim defect, was performed. It is important not only to perform total excision of skeletal cavernous hemangiomas, but to properly reconstruct the defects after the total excision since several complications can arise from an orbital roof and rim defect.

Background: The treatment of choice for fingertip amputation is replantation to restore function and aesthetics. The purpose of this study was to compare the success rates and salvage periods between patients with Tamai's zone I amputation injuries treated with bony fixation and suture fixation., Methods: Fifty-five patients with Tamai's zone I amputations with bony involvement were included in this study. The patients were allocated randomly to two groups treated by bony fixation with Kirschner (K-)wire and suture fixation, respectively. In the bony fixation group (n = 21), the distal phalangeal bone was fixed with K-wire; in the suture fixation group (n = 34), the amputated portion was fixed with sutures alone. The success rate was defined as the percentage of fully viable replanted cases, and the salvage period was defined as extending from the first postoperative day to the cessation of salvation., Results: The success rates for the bony and suture fixation groups were 90.0% and 91.1%, respectively, with no significant difference. The average salvage period was longer in the bony fixation group than in the suture fixation group (8.7 ± 1.25 vs. 6.4 ± 0.98 days; P = 0.01). No case of non-union of the distal phalangeal bone, limitation of motion, or disfigurement was observed in either group., Conclusion: The average salvage period was significantly longer for the bony fixation group, but the success rates did not differ between groups. We suggest that bony fixation is not mandatory in the treatment of Tamai's zone I amputation., (Copyright © 2018 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Laminin subunit beta-3 (LAMB3) encodes one of the three subunits of LM-332, a protein of the extracellular matrix secreted by cultured human keratinocytes. While LAMB3 is involved in the invasive and metastatic abilities of several tumor types, including those found in the colon, pancreas, lung, cervix, stomach, and prostate, its mechanism of action in thyroid cancer has not been investigated previously. Our results show that LAMB3 is up-regulated in papillary thyroid cancer, and that its suppression reduces cell migration/invasion via down-regulation of epithelial‒mesenchymal transition-associated proteins (N-cadherin, vimentin, slug) and inhibition of matrix metalloproteinase 9. LAMB3 suppression also significantly decreases Akt phosphorylation and inhibits the transcription of c-MET, reducing its activation. These results suggest that LAMB3 leads to tumor invasion via Akt activation induced by the HGF/c-MET axis in papillary thyroid cancer cells. Our findings reveal a novel mechanism of action for LAMB3 in papillary thyroid cancer cells.