Exclusive expression of KANK4 promotes myofibroblast mobility in keloid tissues.

Keloids are characterized by abnormal wound healing with excessive accumulation of extracellular matrix. Myofibroblasts are the primary contributor to extracellular matrix secretion, playing an essential role in the wound healing process. However, the differences between myofibroblasts involved in keloid formation and normal wound healing remain unclear. To identify the specific characteristics of keloid myofibroblasts, we initially assessed the expression levels of well-established myofibroblast markers, α-smooth muscle actin (α-SMA) and transgelin (TAGLN), in scar and keloid tissues (n = 63 and 51, respectively). Although myofibroblasts were present in significant quantities in keloids and immature scars, they were absent in mature scars. Next, we conducted RNA sequencing using myofibroblast-rich areas from keloids and immature scars to investigate the difference in RNA expression profiles among myofibroblasts. Among significantly upregulated 112 genes, KN motif and ankyrin repeat domains 4 (KANK4) was identified as a specifically upregulated gene in keloids. Immunohistochemical analysis showed that KANK4 protein was expressed in myofibroblasts in keloid tissues; however, it was not expressed in any myofibroblasts in immature scar tissues. Overexpression of KANK4 enhanced cell mobility in keloid myofibroblasts. Our results suggest that the KANK4-mediated increase in myofibroblast mobility contributes to keloid pathogenesis.

＜Editors' Choice＞ Supernatant from activated omentum accelerates wound healing in diabetic mice wound model.

Diabetic wounds are considered one of the most frequent and severe complications of diabetes mellitus. Recently, the omentum has been used in diabetic wound healing because of its tissue repair properties. The activated omentum is richer in growth factors than the inactivated, thereby contributing to the wound healing process. To further investigate the effect of activated omentum conditioned medium (aOCM) on diabetic wound healing, we injected supernatant from aOCM, saline-OCM (sOCM), inactivated-OCM (iOCM), and medium (M) subcutaneously upon creation of a cutaneous wound healing model in diabetic mice. Wound area (%) was evaluated on days 0, 3, 5, 7, 9, 11, 14, 21, and 28 post-operation. At 9 and 28 d post-operation, skin tissue was harvested and assessed for gross observation, neovascularization, peripheral nerve fiber regeneration, and collagen deposition. We observed that aOCM enhanced the wound repair process, with significant acceleration of epidermal and collagen deposition in the surgical lesion on day 9. Additionally, aOCM displayed marked efficiency in neovascularization and peripheral nerve regeneration during wound healing. Thus, aOCM administration exerts a positive influence on the diabetic mouse model, which can be employed as a new therapy for diabetic wounds.

＜Editors' Choice＞ Long-term outcomes of lateral skull base reconstruction with a free omental flap and facial nerve reconstruction.

In lateral skull base reconstruction, it is necessary to seal the defect in the lateral skull base, fill the dead space, and, sometimes, reconstruct the facial nerve. However, this procedure is difficult to perform with a standard musculocutaneous flap. Therefore, for such cases, an omental flap is used in our hospital because of its flexibility. In this study, we report our experience with the procedure (lateral skull base reconstruction with a free omental flap) and its long-term outcome and facial nerve reconstruction, with special focus on facial nerve recovery. This study is a technical note and a retrospective review. It was conducted in Nagoya University Hospital. Overall, 16 patients (12 women and 4 men; mean age: 55.1 years) underwent lateral skull base reconstruction with a free omental flap after subtotal temporal bone resection or lateral temporal bone resection during 2005-2017. The main outcome measures were postoperative complications and facial nerve recovery: Yanagihara score and House-Brackmann grading system. Complications included partial necrosis and minor cerebrospinal fluid leakage in 2 patients. Facial nerve recovery could be observed more than 12 months after surgery, with a mean Yanagihara score of 19.6 and House-Brackmann grade of 3.60. The free omental flap is a reliable method for lateral skull base reconstruction, especially in cases where facial nerve reconstruction is needed. To the best of our knowledge, this is the first report on facial nerve recovery after lateral skull base reconstruction.

Four-Dimensional Computed Tomographic Image Evaluation of the Change of Condylar Movement With and Without Implant-Supported Removable Prostheses in the Fibular Mandible: A Pilot Case Series Report.

Implant-supported removable prostheses (ISrP) improve the quality of life, especially in patients who underwent mandibular reconstruction, but few studies have focused on the effect of ISrP in the fibular mandible on the function of the temporomandibular joint. The purpose of this pilot case series was to determine the usefulness of four-dimensional computed tomography (4DCT) images for the evaluation of differences in condylar movements with and without ISrP. Three patients who underwent ISrP following segmental mandibulectomy and free-flap reconstruction were evaluated. The participants were instructed to masticate a cookie during the 4DCT scan. The distance between the most anterior and posterior positions of the condyles on the sagittal view of the 4DCT images during the chewing of the cookies was measured and compared with and without ISrP. 4DCT revealed changes in the distances of condylar protrusion with and without wearing ISrP, but there were no obvious differences among the three patients. The 4DCT motion analysis was useful for the evaluation of the effect of wearing ISrP on condylar movements during mastication in patients with mandibular reconstruction and may become a useful objective evaluation method for the functional evaluation of ISrP.

A Novel Risk Model for Predicting Dysphagia after Tongue Reconstruction: A Retrospective Multicenter Study in Japan.

BACKGROUND: There is no consensus on the postoperative outcomes of tongue reconstruction. Therefore, the authors developed a novel risk model for predicting dysphagia after tongue reconstruction. METHODS: This retrospective study was conducted by the Oral Pharyngeal Esophageal Operation and Reconstruction Analytical, or OPERA, group across 31 cancer centers and university hospitals in Japan. A total of 532 patients [390 (73.3%) men and 142 (26.7%) women; median age at surgery, 60 years (range, 15 to 88 years)] who were diagnosed with oral tongue squamous cell carcinoma and underwent tongue reconstruction following glossectomy between 2009 and 2013 were included. Independent risk factors were identified using univariate regression analysis and converted to a binary format for multivariate analysis. An integer value was assigned to each risk factor to calculate a total score capable of quantifying the risk of feeding tube dependence. RESULTS: Overall, 54 patients (10.2%) required a feeding tube at the time of evaluation. Predictive factors for feeding tube dependence were advanced age, lower American Society of Anesthesiologists physical status, low body mass index, lower serum albumin, comorbid hypertension and diabetes, extended tongue defect, resection beyond the tongue, laryngeal suspension, postoperative radiation therapy, and no functional teeth. In multivariate logistic regression analysis, age greater than or equal to 58.5 years, postoperative radiation therapy, wider tongue defect, and body mass index less than 21.27 kg/m 2 earned 6, 4, 3, and 2 points, respectively, for a maximum total score of 15. CONCLUSION: The authors' risk model provides a mathematical tool for estimating the individual risk of postoperative feeding tube dependence before tongue reconstruction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

Salvage surgery for mesenteric lymph node metastasis by resection of the first jejunal flap and reconstruction with the second jejunal flap.

We report a case of a second free jejunal transfer to treat metastasis in the mesenteric lymph node of the first jejunal flap. A 73-year-old man underwent total pharyngolaryngectomy, bilateral neck dissection, and free jejunal transfer for recurrent hypopharyngeal cancer [left pyriform sinus, pT2N0, moderately differentiated squamous cell carcinoma (SCC)] after radiotherapy. Seven years post-surgery, he underwent transoral videolaryngoscopic surgery for oropharyngeal cancer (soft palate, pT1N0, well-differentiated SCC). Ten years after the first jejunal transfer, metastasis was found in the mesenteric lymph node surrounding the jejunal flap's vascular pedicle. Under general anesthesia, resection of the first jejunum including the affected lymph node, and second jejunal transfer were performed. Lymph node pathological examination revealed poorly differentiated SCC, compatible with pharyngeal cancer metastasis. After neck dissection and jejunal flap transfer, lymphatic collateral pathways toward the flap's mesenteric lymph node might form. Possibly, hypopharyngeal or oropharyngeal cancer metastasized via this pathway.

Analysis of Orbital Blowout Fracture Location and Hess Area Ratio.

ABSTRACT: This study aimed to analyze the Hess area ratio (HAR%) in cases of blowout fracture treated in our department and clarify the outline of eye movement disorders in blowout fractures. Patients who underwent surgery for orbital blowout fractures in our department were included. Fracture locations were classified into 5 types (A, outside floor; B, C, anterior and posterior floor; and D, E, anterior and posterior medial wall). The HAR% was compared before and after surgery in eligible cases. The relationship between the fracture location and preoperative HAR% was investigated using multiple regression analysis. The study involved 85 patients. Hess area ratio was higher postoperatively than preoperatively (70.75 ±â€Š18.26 versus 90.06 ±â€Š13.99, P  < 0.01). The postoperative HAR% tended to be higher when the iliac bones were compared to other materials; however, this difference was not significant (90.73 ±â€Š12.91 versus 80.30 ±â€Š17.81, P = 0.178). Fracture locations C and E significantly contributed to the prediction of HAR% as negative regression coefficients (P = 0.024 and 0.013, respectively). The posterior fracture area on both the orbital floor and medial wall contributed to the decrease in preoperative HAR%. This observation indicates that the reconstruction of the posterior region is extremely crucial.

Evaluation of the Effects of Covering With Polyglycolic Acid Sheet on Wound Healing: A Pilot Histopathological Study.

PURPOSE: Although the usefulness of polyglycolic acid (PGA) sheet for wound dressing has been recently reported, its histopathological effect on wound healing is not completely elucidated. This pilot study focused on the neo-epithelium formation and the remaining inflammation. METHODS: Full-thickness defects of 8 mm were created on the back of seven-week-old rats. Four rats were divided into the control (raw surface) group and the PGA group, in which the wounds were covered with a PGA sheet. The wounds were assessed on days seven and 12 after wound creation. The length of neo-epithelium on day seven was measured by referring to Masson's trichrome (MT) and α-smooth muscle actin (α-SMA) staining. The remaining inflammation on days seven and 12 was assessed with ionized calcium-binding adapter molecule 1 (Iba-1) staining. RESULTS: The average values of neo-epithelium length on day seven measured by referring to the borderline between MT staining and α-SMA expression were 959.2 µm in the control group and 582.2 µm in the PGA group. The number of Iba-1-positive cells on day 12 was significantly higher in the PGA group than in the control group. CONCLUSIONS: To assess the neo-epithelium length and the remaining inflammation, the α-SMA, MT, and Iba-1 staining may be appropriate.

Combined treatment using cross-leg free flap and the Masquelet technique: a report of two cases.

We introduce a treatment that combines the cross-leg free flap with the Masquelet technique and describe two cases using this method for bone and soft tissue reconstruction. Both patients were successfully treated and ambulatory. This novel method can be safely performed using the delay technique, indocyanine-green angiography and near-infrared spectroscopy.

Strategy for preventing skin paddle necrosis in mandibular reconstruction with free fibula osteocutaneous flap.

BACKGROUND: Non-thrombotic skin paddle necrosis occasionally occurs during mandibular reconstructions with free fibula osteocutaneous flaps. The number of perforators, size of the skin paddle, and ischemia time of the flap are considered as causes of skin paddle necrosis. The importance of donor side selection has also been highlighted. This study aimed to investigate the leading cause of skin paddle necrosis and the optimal reconstructive procedure. METHODS: A total of 66 patients who underwent mandibular reconstruction using a free fibula osteocutaneous flap were retrospectively analyzed. Skin paddle necrosis, number of cutaneous perforators, size of the skin paddle, and ischemia time of the flap were investigated. An incorrect "laterality" was defined as a skin paddle (septum) covering the reconstruction plate. Donor-site morbidity was recorded. RESULTS: Skin paddle necrosis occurred in 15.2% of patients. An incorrect laterality was associated with a higher incidence of skin paddle necrosis (odds ratio, 22.0; 95% confidence interval, 2.5-195; p = .005). Donor-site morbidity was noted in 18.8% of the patients, without any significant difference in terms of the donor side with and without skin graft (p = .592). The postoperative activities of daily living were not affected. CONCLUSIONS: To prevent skin paddle necrosis, donor side selection is an important safety strategy during mandibular reconstruction with free fibula osteocutaneous flap. The postoperative activities of daily living were found to be little affected by differences in the donor side.

Blowing time ratio and high-resolution manometry to evaluate swallowing function of patients with oral and oropharyngeal cancer.

OBJECTIVE: The blowing time ratio, which is the ratio of the blowing time when the nostrils are open and closed, is significantly correlated with velopharyngeal pressure, not only during speech but also during swallowing. This study aimed to further evaluate the usefulness of the blowing time ratio as a screening tool to evaluate the swallowing pressure of patients treated for oral and oropharyngeal cancers using high-resolution manometery (HRM). METHODS: Ten patients treated for oral or oropharyngeal cancer were recruited for this study. Swallowing pressures at the velopharynx, oropharynx, and upper esophageal sphincter (UES) were measured using HRM. Their correlations with the blowing time ratio were analyzed. RESULTS: The blowing time ratio was significantly correlated with the swallowing pressures of the oropharynx (CC = 0.815, p = 0.004) and the velopharynx (CC = 0.657, p = 0.039), but not of the UES. CONCLUSIONS: The present results further support our previous finding that the blowing time ratio is a useful screening tool to evaluate velopharyngeal and oropharyngeal swallowing pressures in patients treated for oral and oropharyngeal cancer.

Bacterial Colonization of the Condyle in Patients with Advanced Mandibular Osteoradionecrosis: Analysis of Hemimandibulectomy Specimens.

Advanced mandibular osteoradionecrosis (ORN) sometimes requires extended resection (e.g., hemimandibulectomy). Bacterial infection contributes to ORN pathogenesis. To control infection and determine the extent of debridement required, an understanding of bacterial spread within sites of mandibular ORN is important. The current study used a histopathological approach to assess bacterial colonization in the mandibular condyle and elucidate possible paths of bacterial spread towards the mandibular condyle. Four hemimandibulectomy specimens were selected. Areas of bone destruction were macroscopically assessed and confirmed using hematoxylin and eosin staining. Bacterial presence within mandibular condyle was confirmed with Gram staining. Bone exposure was observed in the molar area in all specimens. Macroscopic bone destruction was apparent especially near the medial side of the cortical wall. Gram staining revealed bacterial colonization of the mandibular condyle in three of the four specimens. In conclusion, bacteria tended to spread posteriorly and through the medial side of the mandibular cortical wall. In patients with advanced ORN, the potential for bacterial colonization of the mandibular condyle should be considered during treatment.

Roles of skull base surgery and particle radiotherapy for orbital malignant tumors involving the skull base.

PURPOSE: To investigate the oncological outcomes of orbital malignant tumors invading the skull base. METHODS: A retrospective analysis was conducted on 16 patients with orbital malignant tumors invading the skull base. Eleven patients were treated with skull base surgery, four patients were treated with particle therapies, and one patient was treated with chemoradiotherapy (CRT) as initial treatment. RESULTS: The most frequent histological type was adenoid cystic carcinoma in seven patients, followed by squamous cell carcinoma in two patients. Local recurrence occurred in two of the six surgically treated patients who did not receive postoperative radiotherapy (RT) or CRT. One of them was successfully salvaged by RT, and the other died of disease. With a median follow-up of 24 months, the 2-year overall, local control, and disease-free survival rates of all patients were 82.5%, 87.5%, and 59%, respectively. CONCLUSIONS: Patients with positive surgical margins were at risk of local recurrence. Postoperative RT should be considered for all surgically treated patients.Level of Evidence: 4.

Experimental study on the efficacy of a hybrid artificial nerve: The hot dog method.

INTRODUCTION: We hypothesized that hybrid artificial nerves might overcome the limitations of a nerve conduit by isolating nerve fascicles from autologous nerves. Nerve sacrifice during harvest, a drawback of conventional autologous nerve transplantation, may be reduced by the hot dog method. The hot dog method (based on the morphology of hybrid artificial nerves) adds nerve conduits to autologous nerve fascicles. METHODS: Forty-eight rats with a 10-mm sciatic nerve defect were divided into six groups (n = 8 per group) according to the neural reconstruction method: autologous nerve transplantation, the hot dog method, nerve conduit, nerve fascicle transplantation, sham control, and nerve fascicle isolation were classified as Groups I, II, III, IV, V, and VI, respectively. The sciatic nerve function was assessed in these groups, a histological evaluation was performed, and statistical analyses were conducted based on these data. RESULTS: Group III (nerve conduit) and Group IV (nerve fascicle transplantation) showed the lowest functional and axonal regenerative effects, followed by Group II (hot dog method) and Group I (autologous nerve transplantation). Group VI (nerve fascicle isolation) tended to achieve better recovery in motor function and axonal regeneration than Group I (autologous nerve transplantation). CONCLUSIONS: The hot dog method is simple, safe, and easy to execute. This method can serve as a new neural reconstruction method that uses artificial nerves.

Occurrence and Treatment Outcome of Late Complications After Free Fibula Flap Reconstruction for Mandibular Osteoradionecrosis.

PURPOSE: This study aimed to evaluate the occurrence and treatment outcome of late complications after free fibula osteocutaneous flap reconstruction for mandibular osteoradionecrosis (ORN). METHODS: We enrolled 15 consecutive patients (14 men, one woman; median age 65 years, range 57-80 years) who underwent free fibula reconstruction for advanced mandibular ORN during 2013-2017 with two or more years of follow-up. Late complications included infection, plate exposure, and recurrence at the resection margin. The effect of perioperative antibiotic administration on late complications was also assessed. RESULTS: Late complications occurred in 33.3% (5/15) of patients, including two infections (local and distant), two plate exposures, and two recurrences (plate exposure and recurrence occurred in one patient). Perioperative antibiotic administration duration did not significantly affect the occurrence of postoperative late complications. All late complications were treated without problems. CONCLUSIONS: Late complications after ORN reconstructive surgery are not uncommon, but can be treated properly.

Clinical Evaluation of Unsintered Hydroxyapatite Particles/Poly L-Lactide Composite Device in Craniofacial Surgery.

ABSTRACT: A total of 47 patients who underwent the craniofacial implantation of unsintered hydroxyapatite particles and a poly-L-lactide device were evaluated for clinical local findings and computed tomography (CT) images after about 6 months. Long-term follow-up of 3 patients was done from 5 to 11 years. The patients underwent CT imaging pre- and postoperatively, while local clinical examination was done upon follow-up. For the 3 patients who were followed up for more than 5 years, implant changes were evaluated by using CT. Computed tomography revealed 3 patients of dislocation, 2 patients of insufficient bone union, and 3 patients of implant breakage. All patients healed well with no complications requiring a secondary operation. The CT findings of the long-term cases revealed the following: a plate and screw were still present 5 years postsurgery (patient 1), mesh implants were completely resorbed after 9 years and 6 months (patient 2), and plates were almost resorbed after 11 years but some of their shapes remained (patient 3).The unsintered hydroxyapatite/poly-L-lactide device is useful in the maxillofacial region in terms of strength and radiographic contrast. However, since the absorption rate is slow, it is necessary to keep in mind its long-term radiographic detectability and the possibility of late-onset granuloma.

Perineal reconstruction with pedicled rectus abdominis myocutaneous flap after posterior pelvic exenteration -A 3D model study.

INTRODUCTION: Limited literature exists regarding the positional relationship between the pedicled-rectus abdominis myocutaneous (p-RAMC) flap and residual pelvic organs post posterior pelvic exenteration (PPE). PRESENTATION OF CASE: Four patients underwent PPE and reconstruction with a p-RAMC flap. After harvesting the p-RAMC flap with the deep inferior epigastric artery and veins as the vascular pedicle, the intra-pelvic shortest pathway of the flap was created. We dissected the subcutaneous tissues of the flap donor site toward the perineal defect along the inner wall of the pelvis. The pubic origin of the rectus abdominis muscle was preserved. A three-dimensional model was constructed using an image processing software. The vascular pedicle ran almost linearly along the inner wall of the pelvis. The muscle belly was placed on the pelvic floor through the posterior wall of the urinary bladder which filled the dead space of the resected area. All flaps survived without significant complications. DISCUSSION: Assigning the cranial side of the flap to the perineum and caudal side to the pelvic floor could reduce postoperative intrapelvic complications. By preserving the pubic origin of the rectus abdominis muscle, a shock absorber of the pedicle of the flap was created, preventing over-traction of the flap while passing through the intrapelvic pathway. CONCLUSION: A p-RAMC flap via intra-pelvic shortest pathway is an ideal reconstructive method for large skin defect in perineal area after PPE.

Wire Myography for Continuous Estimation of the Optimal Concentration of Topical Lidocaine as a Vasodilator in Microsurgery.

BACKGROUND: Intraoperative vasospasm during reconstructive microvascular surgery is often unpredictable and may lead to devastating flap loss. Therefore, various vasodilators are used in reconstructive microsurgery to prevent and relieve vasospasm. Lidocaine is a vasodilator commonly used in microvascular surgery. Although many reports have described its in vitro and in vivo concentration-dependent vasodilatory effects, limited studies have examined the pharmacological effects of lidocaine on blood vessels in terms of persistence and titer. METHODS: In this study, the vasodilatory effect of lidocaine was examined by using the wire myograph system. Abdominal aortas were harvested from female rats, sliced into rings of 1-mm thickness, and mounted in the wire myograph system. Next, 10, 5, 2, and 1% lidocaine solutions were applied to the artery, and the change in vasodilation force, persistence of the force, and time required to reach equilibrium were measured. RESULTS: The vasodilatory effect was confirmed in all groups following lidocaine treatment. Although strong vasodilation was observed in the 10% lidocaine group, it was accompanied by irreversible degeneration of the artery. Vasodilation in the 1% lidocaine group was weaker than that in the other groups 500 seconds after lidocaine addition (p < 0.05). Between the 5 and 2% lidocaine groups, 5% lidocaine showed a stronger vasodilatory effect 400 to 600 seconds after lidocaine addition (p < 0.01); however, there was no significant difference in these groups after 700 seconds. Additionally, there was no difference in the time required for the relaxation force to reach equilibrium among the 5, 2, and 1% lidocaine groups. CONCLUSION: Although our study confirmed the dose-dependent vasodilatory effect of lidocaine, 5% lidocaine showed the best vasodilatory effect and continuity with minimal irreversible changes in the arterial tissue.