Endoscope-assisted extracapsular dissection of benign parotid tumors through a single cephaloauricular furrow incision versus a conventional approach.

BACKGROUND: A few modified approaches have been reported for performing endoscope-assisted dissections of benign parotid tumors, but none that use incisions totally hidden in a natural furrow. This study evaluated the feasibility of performing endoscope-assisted extracapsular dissections of benign parotid tumors using a single cephaloauricular furrow incision. METHODS: Forty-six patients with benign parotid superficial lobe tumors were randomly divided into two groups: an endoscope-assisted (21 patients) group or a conventional (25 patients) surgery group. Perioperative and postoperative outcomes of the patients were evaluated, including the maximum diameter of the tumors, length of the incision, operating time, estimated blood loss during the operation, amount and duration of drainage, satisfaction scores based on the cosmetic results, perioperative complications, and follow-up information. RESULTS: The diameters of the tumors were comparable between the groups, and all operations were successfully performed as planned. The mean length of the incision in the endoscope-assisted group (3.6 ± 0.5 cm) was significantly shorter than that in the conventional group (9.1 ± 1.9). Meanwhile, the intraoperative blood loss, amount of drainage, perioperative complications, and cosmetic outcomes were all improved in the endoscope-assisted group. No tumor recurrence was found during 11-40 months of follow-up. CONCLUSIONS: Cephaloauricular furrow incisions were totally and naturally hidden in this procedure. Endoscope-assisted extracapsular dissections of benign parotid tumors via a small cephaloauricular furrow incision were found to be feasible and reliable, providing a minimally invasive approach and a satisfactory appearance.

Virtual Surgical Planning in Precise Maxillary Reconstruction With Vascularized Fibular Graft After Tumor Ablation.

PURPOSE: Reconstruction of maxillary and midfacial defects due to tumor ablation is challenging to conventional operation. The purposes of this study are to evaluate the precise 3-dimensional position of the fibular flap in reconstruction of maxillary defects assisted by virtual surgical planning and to assess the postoperative outcomes compared with conventional surgery. MATERIALS AND METHODS: We retrospectively reviewed 18 consecutive patients who underwent maxillary reconstruction with a vascularized fibular flap assisted by virtual surgical planning after maxillary or midfacial tumor ablation. Conventional surgery was performed in another 15 patients. Proplan CMF surgical planning (Materialise, Leuven, Belgium) was performed preoperatively in the virtual planning group. Fibular flaps were harvested and underwent osteotomy assisted by prefabricated cutting guides, and the maxilla and midface were resected and reconstructed assisted by the prefabricated cutting guides and templates in the virtual planning group. The operative time and fibular flap positions were evaluated in the 2 groups. Postoperative fibular positions of the maxillary reconstruction were compared with virtual plans in the virtual planning group. The postoperative facial appearance and occlusal function were assessed. RESULTS: The operations were performed successfully without complications. The ischemia time and total operative time were shorter in the virtual planning group than those in the conventional surgery group (P < .05). High precision of the cutting guides and templates was found on both the fibula and maxilla in the virtual planning group. The positions of the fibular flaps, including the vertical and horizontal positions, were more accurate in the virtual planning group than those in the conventional surgery group (P < .05). Bone-to-bone contact between the maxilla and fibular segments was more precise in the virtual planning group (P < .05). Postoperative computed tomography scans showed excellent contour of the fibular flap segments in accordance with the virtual plans in the virtual planning group. All patients were alive with no evidence of disease. Functional mandibular range of motion, good occlusion, and an ideal facial appearance were observed in the virtual planning group. CONCLUSIONS: Virtual surgical planning appears to achieve precise maxillary reconstruction with a vascularized fibular flap after tumor ablation, as well as an ideal facial appearance and function after dental rehabilitation. The use of prefabricated cutting guides and plates eases fibular flap molding and placement, minimizes operating time, and improves clinical outcomes.

Novel Local Full-Thickness Skin Grafts for Closure of Free Fibular Osteocutaneous Flap Donor Sites.

PURPOSE: The fibular flap donor site after skin paddle harvest is usually covered with abdominal full-thickness skin grafts. However, this kind of skin graft creates an inevitable third operative area and additional esthetic damage. The aim of this report was to present a novel approach to manage fibular donor site defects using a full-thickness skin graft from the adjacent area and avoid further esthetic damage in a third area. MATERIALS AND METHODS: Seventeen patients underwent mandibular and maxillary defect reconstruction using free fibular osteocutaneous flaps and the fibular donor-site defects were covered with full-thickness skin grafts from the adjacent area. The skin harvesting sites were closed primarily. RESULTS: The skin donor sites were closed without dehiscence in all cases. Fifteen full-thickness skin grafts survived completely, whereas 2 grafts were partial failures. There were no complete skin graft losses. All fibular osteocutaneous flaps were viable, and the recipient sites had no complications. CONCLUSIONS: This study shows that adjacent full-thickness skin grafts provide a straightforward and reliable technique for closure of the free fibular osteocutaneous flap donor site. The primary advantage of this technique is the avoidance of a third surgical site, an additional surgical scar, and subsequent additional esthetic impairment.

Liquid nitrogen cryotherapy for lip mucous membrane venous malformation in infants.

OBJECTIVE: Lip mucous membrane venous malformations are common benign lesions in infants. This clinical study evaluates the efficacy and safety of liquid nitrogen cryotherapy used to treat this condition. METHODS: A total of 84 pediatric patients undergoing liquid nitrogen cryotherapy for venous malformations involving the lips were reviewed, with 45 males and 39 females treated. The overall median age at mucous membrane venous malformation diagnosis was 5.6 months (range 2-18 months). The venous malformations involved the vermilion of the lower lip in 44 cases, the vermilion of the upper lip in 31 cases, and both vermilions in 9 cases. RESULTS: No complications due to anesthesia occurred. After a follow-up period of 2-38 months (mean 25 months), 65 lesions (77.4 %) were completely involuted, 14 lesions (16.7 %) were mostly involuted, and 5 lesions (5.9 %) were partially involuted; no lesions showed a minor amount of involution. CONCLUSIONS: Liquid nitrogen cryotherapy is an effective, simple, and safe management tool for mucous membrane venous malformations of the lip in infants.

Minimally invasive selective neck dissection: a prospective study of endoscopically assisted dissection via a small submandibular approach in cT(1-2_N(0) oral squamous cell carcinoma.

BACKGROUND: Selective neck dissection (SND) in clinical N0 (cN0) cases of oral squamous cell carcinoma (SCC) has been performed by surgeons using a retroauricular or modified facelift approach with robotic or endoscopic assistance. However, these procedures provide cosmetic satisfaction at the cost of possible maximal invasiveness. In this prospective study, we introduced and evaluated the feasibility as well as surgical invasiveness and cosmetic outcome of endoscopically-assisted SND via a small submandibular approach. METHODS: Forty-four patients with cT1-2N0 oral SCC (OSCC) were randomly divided into two groups of endoscopically-assisted SND and conventional SND. Perioperative and postoperative outcomes of patients were evaluated, including the length of the incision, operating time for neck dissection, estimated blood loss during the operation, amount and duration of drainage, total hospitalization period, total number of lymph nodes retrieved, satisfaction scores based on the cosmetic results, perioperative local complications, shoulder syndrome, and follow-up information. RESULTS: The mean operation time in the endoscopically-assisted group (126.04 ± 12.67 min) was longer than that in the conventional group (75.67 ± 16.67 min). However, the mean length of the incision was 4.33 ± 0.76 cm in the endoscopically-assisted SND group, and the amount and duration of drainage, total hospital stay, postoperative shoulder pain score, and cosmetic outcomes were superior in the endoscopically-assisted SND group. Additionally, the retrieved lymph nodes and complications were comparable. CONCLUSIONS: Endoscopically-assisted SND via a small submandibular approach had a longer operation time than the conventional approach. However, endoscopically-assisted SND was feasible and reliable while providing minimal invasiveness and satisfactory appearance.

A role for cancer-associated fibroblasts in inducing the epithelial-to-mesenchymal transition in human tongue squamous cell carcinoma.

OBJECTIVES: Lymph node metastasis is a prominent clinical feature of tongue squamous cell carcinoma (TSCC) and is associated with a higher mortality rate. Carcinoma-associated fibroblasts (CAFs), a major component of the tumor microenvironment (TME), play an important role in tumor progression, and are associated with a poor prognosis. The aim of this study was to examine the role of CAFs in promoting the invasion of TSCC through the epithelial-to-mesenchymal transition (EMT). MATERIALS AND METHODS: A series of matched CAF and normal fibroblast (NF) pairs were assessed for cell morphology and for the expression of alpha smooth muscle actin (α-SMA), stromal cell-derived factor-1 (SDF1), fibroblast-activating protein (FAP), vimentin, and cytokeratin (CK) markers. Transwell assays, Western blot analysis, reverse transcription-PCR, and immunofluorescence staining were used to assess the role of CAFs, as compared to that of NFs, in promoting proliferation, migration, invasion, and EMT in TSCC. RESULTS: Both CAF and NF primary cultures expressed vimentin but not CK. CAFs showed significantly higher α-SMA protein levels, SDF1 secretion, and mRNA levels of α-SMA, SDF1, and FAP. We also found that co-culture with CAFs enhanced the proliferation and invasion of SCC9 cells. Moreover, co-culture with CAFs induced upregulation of the EMT markers fibronectin and vimentin, downregulation of E-cadherin, and enhanced invasion in SCC9 cells. CONCLUSION: These results suggest that CAFs induce EMT marker expression and functional changes in TSCCs.

Extracellular matrix metalloproteinase inducer expression in salivary gland tumors: a correlation with microvessel density.

The purpose of this study was to investigate the expression pattern of extracellular matrix metalloproteinase inducer (EMMPRIN) as well as the correlation between EMMPRIN and microvessel density (MVD) in salivary gland tumors. Extracellular matrix metalloproteinase inducer expression and MVD were examined immunohistochemically on paraffin-embedded tissue specimens from 95 patients with salivary gland tumors, who underwent surgical resection from 1998 to 2006. Reverse transcription-polymerase chain reaction was used to monitor EMMPRIN mRNA expression in frozen samples. Extracellular matrix metalloproteinase inducer expression in mucoepidermoid carcinomas and adenoid cystic carcinomas was significantly higher than in normal salivary gland tissues and pleomorphic adenomas (P < 0.05). The MVD of mucoepidermoid carcinomas and adenoid cystic carcinomas was significantly higher compared with pleomorphic adenomas (P < 0.05). The MVD of the EMMPRIN-positive expression group was significantly higher than the MVD of the EMMPRIN-negative expression group (P < 0.05). Extracellular matrix metalloproteinase inducer mRNA expression in malignant salivary gland tumors was higher than that in pleomorphic adenomas (P < 0.05). This study suggests that EMMPRIN expression is an important feature of malignant salivary gland tumors and can be used as a biologic marker to characterize salivary gland tumors. Extracellular matrix metalloproteinase inducer is also a positive angiogenic factor in salivary gland tumors.

"Five-point eight-line" anatomic flap design for precise hemitongue reconstruction.

BACKGROUND: Reconstruction of hemiglossectomy defects requires careful flap design to avoid adverse functional and aesthetic outcomes. METHODS: Hemitongue specimens were obtained from minipigs to study the three-dimensional anatomy and to define anatomic landmarks for precise measurements of flap requirement. The concept developed in animal models was then applied to hemiglossectomy reconstruction in clinical practice. Sixty-one patients were randomly enrolled into the following two groups: a "five-point eight-line segment" (FIPELS) flap design group (28 patients) and a conventional group (33 patients). Functional and aesthetic outcomes were compared between the two groups. RESULTS: All flaps designed with the FIPELS technique matched the hemiglossectomy defects without the need for flap trimming, thus reducing the operating time (P = .03). Swallowing functions, speech intelligibility, and aesthetic outcomes were superior in the FIPELS group than that in the conventional group (P < .05). CONCLUSIONS: The FIPELS flap design for hemiglossectomy reconstruction yields improved functional and aesthetic outcomes compared to a conventional flap design.

CRISPR/Cas9-Mediated Treatment Ameliorates the Phenotype of the Epidermolytic Palmoplantar Keratoderma-like Mouse.

CRISPR/Cas9 has been confirmed as a distinctly efficient, simple-to-configure, highly specific genome-editing tool that has been used to treat monogenetic disorders. Epidermolytic palmoplantar keratoderma (EPPK) is a common autosomal dominant keratin disease resulting from dominant-negative mutation of the KRT9 gene, and it has no effective therapy. We performed CRISPR/Cas9-mediated treatment on a knockin (KI) transgenic mouse model that carried a small indel heterozygous mutation of Krt9, c.434delAinsGGCT (p.Tyr144delinsTrpLeu), which caused a humanized EPPK-like phenotype. The mutation within exon 1 of Krt9 generated a novel protospacer adjacent motif site, TGG, for Cas9 recognition and cutting. By delivering lentivirus vectors (LVs) encoding single-guide RNAs (sgRNAs) and Cas9 that targeted Krt9 sequence into HeLa cells engineered to constitutively express wild-type and mutant keratin 9 (K9), we found the sgRNA was highly effective in reducing expression of the mutant K9 protein in vitro. We injected the LV into the fore-paws of adult KI-Krt9 mice three times every 8 days and found that the expression of K9 decreased ∼14.6%. The phenotypic mitigation was revealed by restoration of the abnormal differentiation and aberrant proliferation of the epidermis. Our data are the first to show that CRISPR/Cas9 is a potentially powerful therapeutic option for EPPK and other PPK subtypes.

IncRNA H19 promotes tongue squamous cell carcinoma progression through ß-catenin/GSK3ß/EMT signaling via association with EZH2.

H19 is involved in tumor metastasis and associated with tumor progression. Enhancer of zest homolog 2 (EZH2) is overexpressed in multiple cancer types and correlates with tumor proliferation, epithelial-mesenchymal transition, and poor prognosis. However, the interaction between H19 and EZH2 to promote tongue squamous cell carcinoma (TSCC) progression remains largely uncharacterized. Insitu hybridization and quantitative reverse-transcription PCR (qRT-PCR) were performed to measure H19 expression in primary TSCC and adjacent normal tissues and cell lines. EZH2 expression was determined by immunohistochemistry in matched primary TSCC and adjacent normal tissues. The correlation between H19 and EZH2 expression and clinicopathological characteristics were analyzed. The roles of H19 in cell proliferation, apoptosis, and invasion were analyzed using a H19-targeted lentivirus. Western blot and qRT-PCR were carried out to detect downstream signal pathway changes. Expression levels of downstream signaling proteins in primary TSCC tissues and adjacent normal tissues were analyzed by immunohistochemistry. H19 and EZH2 were upregulated in TSCC tissues compared to matched normal tissues, and significantly correlated with WHO grade, lymph node metastasis, and poor prognosis. H19 silencing attenuated cell proliferation, apoptosis, and invasion in vitro. H19 knockdown inhibited the activation of ß-catenin/GSK-3ß/cyclin D1/c-myc, upregulated E-cadherin and zonula occludens-1 (ZO-1), and inhibited N-cadherin, vimentin, Snail1, Twist1, and ZEB1. Silencing H19 expression also inhibited tumor progression and lung metastasis in an animal model. Our findings indicate that H19 promotes TSCC progression through association with EZH2, and affects downstream ß-Catenin/GSK3ß/EMT signaling, suggesting that H19 inhibition might be a potential target for the treatment of TSCC.

A comparative study of the endoscopy-assisted transoral approach versus external approaches for the resection of large benign parapharyngeal space tumors.

OBJECTIVE: The advantages and limitations of the endoscopy-assisted transoral approach (EATA) and external approaches (EAs) in resection of parapharyngeal space tumors (PSTs) remain unclear. In our study, we compared the use of the EATA and the EAs for the resection of large, benign PSTs. STUDY DESIGN: Forty-four patients with PSTs were divided into the EATA and EA groups. The perioperative and postoperative outcomes of the patients were evaluated. RESULTS: All of the tumors were completely removed. However, the procedure was converted to an open procedure for four patients in the EATA group and for six patients in the EA group who required endoscopic assistance. The intraoperative blood loss, amount and duration of drainage, postoperative pain, total hospital stay, and cosmetic outcomes were superior in the EATA group (P < .05). CONCLUSIONS: Use of the EATA for resection of large, benign PSTs decreased the surgical invasiveness of the procedure and resulted in better aesthetic outcomes. However, use of the combined surgical approach allowed for improved access for the resection of PSTs.

Postoperative immune response and surgical stress in selective neck dissection: Comparison between endoscopically assisted dissection and open techniques in cT1-2N0 oral squamous cell carcinoma.

BACKGROUND: Endoscopically assisted selective neck dissection (SND) has recently been applied in clinical N0 cases of oral squamous cell carcinoma (OSCC). However, nothing is known of the immune response after surgery. METHODS: A total of 60 patients with cT1-2N0 OSCC randomly underwent endoscopically assisted SND and open operations. The serum levels of IL-6, IL-8, IL-10, IL-1b, TNF-a, CRP, cortisol, ACTH, and growth hormone were analyzed before the start of the surgery (T0) and at 2 (T1), 6 (T2), 24 (T3), and 72 h (T4) after surgery. RESULTS: A total of 31 patients were randomized for endoscopic SND, whereas 29 underwent open procedures. The release of IL-6, IL-10 and CRP was significantly lower in the endoscopic group than in the open surgery group (p < 0.05), and cortisol levels were also lower in the endoscopic group (p < 0.05). CONCLUSIONS: Endoscopic SND could effectively provide lower inflammatory responses and surgical stress, reducing peri-operative trauma and accelerating recovery.

Percutaneous sclerotherapy of arteriovenous malformations of the face using fibrin glue combined with OK-432 and bleomycin after embolisation.

Congenital arteriovenous malformations (AVM) in the maxillofacial region are rare, but potentially life-threatening, vascular lesions. Here we review our experience of 13 patients with AVM of the facial soft tissues who were treated using percutaneous sclerotherapy with fibrin glue combined with OK-432 and bleomycin after embolisation. The mean (range) follow-up was 27 (14-58) months. Three of the lesions were completely controlled, eight were nearly completely controlled, and the other two were partly controlled. Our experience is that percutaneous sclerotherapy of arteriovenous malformations of the face using fibrin glue combined with OK-432 and bleomycin after embolisation is safe and effective.

Extended vertical lower trapezius island myocutaneous flap versus pectoralis major myocutaneous flap for reconstruction in recurrent oral and oropharyngeal cancer.

BACKGROUND: The purpose of this study was to compare the use of an extended vertical lower trapezius island myocutaneous flap (TIMF) and a pectoralis major myocutaneous flap (PMMF). METHODS: A total of 39 patients with advanced recurrent oral and oropharyngeal squamous cell carcinoma (SCC) underwent salvage surgery followed by placement of either an extended lower vertical TIMF or PMMF for reconstruction. Twenty-one patients received extended lower vertical TIMFs, whereas 18 received PMMFs. RESULTS: The pedicle length of the TIMF was longer than that of the PMMF, and the skin paddle of the TIMF was both wider and longer than the PMMF. No major complication developed in any of the patients. The TIMF group experienced a lower rate of minor flap failure than did the PMMF group. CONCLUSION: Use of an extended vertical lower TIMF, which has a longer pedicle flap and a larger skin paddle than a PMMF, is optimal for reconstruction of major defects. © 2015 Wiley Periodicals, Inc. Head Neck 38: E159-E164, 2016.

Intraoral lining with the fibular osteomyofascial flap without a skin paddle during maxillary and mandibular reconstruction.

BACKGROUND: To achieve an ideal intraoral lining, we harvest the fibular osteomyofascial flap to avoid the common embarrassment caused by the fibular osteomyocutaneous flap, and we report on our experience with this technique in this article. METHODS: Twenty-eight patients underwent reconstruction of the maxilla and mandible using an osteomyofascial free fibula flap after oncologic ablation. Data, including the size of the fascial flaps, the number of debulking operations, the complications at both the donor and recipient sites, and the dental rehabilitation, were collected. RESULTS: All fascial flaps survived and were remucosalized, except one with partial necrosis. None of the patients in the osteomyofascial group required an additional debulking operation, and 82% of the patients (23 of 28) had conventional dentures and showed good chewing function and cosmetic results. CONCLUSION: The fibular osteomyofascial flap yielded a more anatomic solution for oral mucosal defects, obviating the need for additional debulking and potentially reducing donor-site wound problems. © 2015 Wiley Periodicals, Inc. Head Neck 38: E832-E836, 2016.

A Small Indel Mutant Mouse Model of Epidermolytic Palmoplantar Keratoderma and Its Application to Mutant-specific shRNA Therapy.

Epidermolytic palmoplantar keratoderma (EPPK) is a relatively common autosomal-dominant skin disorder caused by mutations in the keratin 9 gene (KRT9), with few therapeutic options for the affected so far. Here, we report a knock-in transgenic mouse model that carried a small insertion-deletion (indel) mutant of Krt9, c.434delAinsGGCT (p.Tyr144delinsTrpLeu), corresponding to the human mutation KRT9/c.500delAinsGGCT (p.Tyr167delinsTrpLeu), which resulted in a human EPPK-like phenotype in the weight-stress areas of the fore- and hind-paws of both Krt9(+/mut) and Krt9(mut/mut) mice. The phenotype confirmed that EPPK is a dominant-negative condition, such that mice heterozygotic for the K9-mutant allele (Krt9(+/mut)) showed a clear EPPK-like phenotype. Then, we developed a mutant-specific short hairpin RNA (shRNA) therapy for EPPK mice. Mutant-specific shRNAs were systematically identified in vitro using a luciferase reporter gene assay and delivered into Krt9(+/mut) mice. shRNA-mediated knockdown of mutant protein resulted in almost normal morphology and functions of the skin, whereas the same shRNA had a negligible effect in wild-type K9 mice. Our results suggest that EPPK can be treated by gene therapy, and this has significant implications for future clinical application.

Synchronous reconstruction of bilateral osteoradionecrosis of the mandible using a single fibular osteocutaneous flap in patients with nasopharyngeal carcinoma.

BACKGROUND: The reconstruction of bilateral osteoradionecrosis (ORN) of mandibular defects using a single free bone flap is rarely performed because extensively radiated neck tissue with severe fibrosis is usually unsuitable for vascularized reconstruction. METHODS: Thirty-one patients with nasopharyngeal carcinoma (NPC) underwent bilateral reconstruction of advanced ORN in the mandible using a single fibular osteocutaneous flap. Clinical factors associated with the operation were assessed, including classification of mandible defects, types of recipient vessels, perioperative complications, and postoperative outcomes. RESULTS: All of the fibular osteocutaneous flaps survived completely, with the exception of 1 inner skin paddle that presented partial necrosis in a reconstruction of through-and-through defects. All patients experienced an improvement in cosmetic results 6 months after the reconstruction, whereas 23 patients experienced improved mouth opening compared to the preoperative condition. CONCLUSION: Advanced bilateral ORN in patients with NPC could be synchronously reconstructed with a single fibular osteocutaneous flap. © 2015 Wiley Periodicals, Inc. Head Neck 38: E-E, 2016.

Tumor necrosis factor α induces myofibroblast differentiation in human tongue cancer and promotes invasiveness and angiogenesis via secretion of stromal cell-derived factor-1.

OBJECTIVES: Cancer-associated fibroblasts (CAFs) play an important role in tumor progression and are associated with a poor prognosis. Tumor necrosis factor α (TNFα) has been involved in growth and metastasis associated with epithelial-mesenchymal transition (EMT) in many types of cancers. However, the relationship among the TNFα, activation of CAFs and their tumor-promoting effects on tongue squamous cell carcinoma (TSCC) remain obscure. MATERIALS AND METHODS: A series of matched primary CAFs and normal fibroblasts (NFs) pairs were cultured, and additionally two TSCC cell lines SCC9 and CAL27, were treated with TNFα or CAFs derived stromal cell-derived factor-1 (SDF1) respectively to study invasion and EMT in vitro. In addition, NFs were treated with TNFα to detect the expression of myofibroblast markers, invasion, induced collagen gel contraction and enhanced cancer metastasis. Finally, invasion and angiogenesis of human vein endothelial cells (HUVECs) treated with TNFα and CAFs derived SDF1 was measured. RESULTS: TNFα and CAFs-derived SDF1 induced TSCC cells metastasis and EMT separately. TNFα facilitated the transformation of NFs to CAFs-like fibroblasts, which was accompanied by acquisition of similar myofibroblast markers expression and malignant function to CAFs. Furthermore, TNFα and CAFs derived SDF1 also promoted invasion and angiogenesis of HUVECs. CONCLUSION: These results suggest that TNFα may not only directly but also indirectly enhance cancer metastasis, EMT and angiogenesis formation in tongue cancer through myofibroblast differentiation via SDF1 secretion.

miR-483-5p determines mitochondrial fission and cisplatin sensitivity in tongue squamous cell carcinoma by targeting FIS1.

Mitochondria play an important role in the initiation of apoptosis. However, whether cisplatin can induce apoptosis by initiating a mitochondrial fission pathway and the mechanism underlying this effect remain poorly understood. In this study, we show that the mitochondrial fission protein FIS1 is upregulated upon cisplatin treatment in tongue squamous cell carcinoma (TSCC) cells. FIS1 knockdown can attenuate mitochondrial fission and cisplatin sensitivity. We found that FIS1 is a direct target of miR-483-5p and that miR-483-5p can inhibit mitochondrial fission and cisplatin sensitivity in vitro and in vivo. Furthermore, we found that miR-483-5p and FIS1 are significantly associated with cisplatin sensitivity and with overall survival in patients with TSCC in a retrospective analysis of multiple centers. This study revealed that a novel mitochondrial fission pathway composed of miR-483-5p and FIS1 regulates cisplatin sensitivity. The modulation of miR-483-5p and FIS1 levels may provide a new approach for increasing cisplatin sensitivity.

Use of a folded reverse facial-submental artery submental island flap to reconstruct soft palate defects following cancer ablation.

INTRODUCTION: Although several techniques have been described for the repair of soft palate defects, soft palate reconstruction remains challenging. This study was performed to evaluate swallowing and speech functions in patients undergoing placement of folded reverse facial-submental artery submental island flaps (FRFF) to reconstruct soft palate defects following cancer ablation. MATERIALS AND METHODS: FRFFs were designed for eight patients with soft palate defects resulting from soft palatal squamous cell carcinoma ablation. The clinical stages of tumours were I in two patients, II in four patients, and III in two patients. FRFFs were created to reconstruct soft palate defects. Swallowing and speech functions were evaluated 3 months postoperatively. RESULTS: One minor flap failure occurred, but all flaps survived. No donor-site problem occurred. Five patients managed ingestion of a solid diet, two managed a soft diet, and one remained on a liquid diet. Six patients achieved normal speech, one achieved intelligible speech, and one retained slurred speech. The patients were followed for 8-48 months; seven patients were living with no evidence of disease, and one was living with disease. CONCLUSIONS: The FRFF is reliable for soft palate defect reconstruction following cancer ablation and can achieve satisfactory swallowing and speech functions.