Tryptase-Positive Mast Cells Promote Adipose Fibrosis in Secondary Lymphedema through PDGF.

Lymphedema is a chronic and progressive condition that causes physical disfigurement and psychological trauma due to the accumulation of lymphatic fluid in the interstitial space. Once it develops, lymphedema is difficult to treat because it leads to the fibrosis of adipose tissue. However, the mechanism behind this remains unclear. The purpose of this study was to investigate the involvement of mast cells (MCs) in the adipose tissues of patients with lymphedema. We found that fibrosis spread through blood vessels in the adipose tissues of lymphedema patients, and the expression of the collagen I and III genes was significantly increased compared to that of those in normal adipose tissue. Immunostaining of vimentin and α-smooth muscle actin showed that fibroblasts were the main cellular components in severely fibrotic regions. Toluidine blue staining confirmed a significant increase in the number of MCs in the adipose tissues of lymphedema patients, and immunostaining of serial sections of adipose tissue showed a significant increase in the number of tryptase-positive cells in lymphedema tissues compared with those in normal adipose tissues. Linear regression analyses revealed significant positive correlations between tryptase and the expressions of the TNF-α, platelet-derived growth factor (PDGF)-A, and PDGFR-α genes. PDGF-A-positive staining was observed in both fibroblasts and granules of tryptase-positive MCs. These results suggest that MC-derived tryptase plays a role in the fibrosis of adipose tissue due to lymphedema directly or in cooperation with other mediators.

Synchondrosis fusion contributes to the progression of postnatal craniofacial dysmorphology in syndromic craniosynostosis.

Syndromic craniosynostosis (CS) patients exhibit early, bony fusion of calvarial sutures and cranial synchondroses, resulting in craniofacial dysmorphology. In this study, we chronologically evaluated skull morphology change after abnormal fusion of the sutures and synchondroses in mouse models of syndromic CS for further understanding of the disease. We found fusion of the inter-sphenoid synchondrosis (ISS) in Apert syndrome model mice (Fgfr2S252W/+ ) around 3 weeks old as seen in Crouzon syndrome model mice (Fgfr2cC342Y/+ ). We then examined ontogenic trajectories of CS mouse models after 3 weeks of age using geometric morphometrics analyses. Antero-ventral growth of the face was affected in Fgfr2S252W/+ and Fgfr2cC342Y/+ mice, while Saethre-Chotzen syndrome model mice (Twist1+/- ) did not show the ISS fusion and exhibited a similar growth pattern to that of control littermates. Further analysis revealed that the coronal suture synostosis in the CS mouse models induces only the brachycephalic phenotype as a shared morphological feature. Although previous studies suggest that the fusion of the facial sutures during neonatal period is associated with midface hypoplasia, the present study suggests that the progressive postnatal fusion of the cranial synchondrosis also contributes to craniofacial dysmorphology in mouse models of syndromic CS. These morphological trajectories increase our understanding of the progression of syndromic CS skull growth.

Secondary Reconstruction of Late Deformities of the Orbitozygomaticomaxillary Complex using a Halo Device.

Reconstructing late deformities of the orbitozygomaticomaxillary complex after inadequate treatment of facial fractures requires zygomatic osteotomy to reposition the bony fragments to their anatomical position. However, confirming the position of the bone fragments can be challenging due to the loss of anatomic landmarks caused by bone remodeling, and swelling resulting from surgery, which might hinder locating the bone from the body surface. Here, the authors describe fixation of the halo of the Blue Device multi-vector distraction system to the patient's ear canal, with alignment of the position of the zygoma by measuring the distances between the halo and zygoma using several reference points. This technique allows for measurement not only from the body surface using a K-wire but also directly to the bone using a needle. The authors applied this technique in 2 cases of post-traumatic deformities after complex zygomatic fractures. Both cases achieved an almost symmetrical appearance of the infraorbital region.

Orbital Roof Decompression and Transposition of Orbital Contents for Treatment of Orbital Deviation Associated With Fibrous Dysplasia.

A 25-year-old male was admitted to our institute complaining of caudal deviation of orbit. Surgery was performed through a coronal incision, a subtarsal incision, and a lynch incision. The periosteum of the orbital roof was raised, and the supraorbital wall was shaved cephalad in reference to the nonaffected side. Then the periosteum was incised from the inferior margin of the orbit to the medial and lateral palpebral ligaments, and the periosteum of the orbital floor was raised until the inferior orbital fissure. After the circumferential intraorbital periosteal detachment, the orbital contents could be readily moved cephalad ward. The outer table of the calvarial bone was transplanted to the orbital floor, and the palpebral ligaments were fixed 5 mm cranially. In the 5-year follow-up, the patient's visual function was normal, and no recurrence of fibrous dysplasia was observed.

Application of augmented reality (AR) technology to locate the cutaneous perforator of anterolateral thigh perforator flap: A case report.

Multi-detector row computed tomography (MDCT) makes it possible to visualize the peripheral perforators of the anterolateral thigh (ALT) flap. However, to transfer the preoperative MDCT angiography data to the operative field requires effective techniques. In this report, we describe an application of augmented reality (AR) technology to harvest the anterolateral thigh flap. A 36-year-old female presented with a T2N2 squamous cell carcinoma of the lateral tongue. The patient underwent hemiglossectomy and microsurgical reconstruction using the left ALT flap. Three dimensional (3D) images the vascular image, vascular with muscles and vascular with outline of the thigh ware prepared. Then these images were exposed to an AR device. The location of the perforator was determined using the 3D vascular image on AR. The intraoperative location of the cutaneous perforator corresponded with the predicted location which was confirmed using the AR technique. A 6 × 15 cm left ALT flap was transferred to the defect. Microsurgical anastomosis was performed on the left superior thyroid artery and the internal jugular vein. There were no complications during the postoperative course. At the 6-month follow-up, the patient showed no evidence of flap and donor site complications. Our experience suggests that AR technology may effectively support the transfer of MDCT angiography images onto surgical sites.

Treatment of scarring alopecia from trauma and surgical procedures in young patients using follicular unit hair transplantation.

INTRODUCTION: Hair loss due to scarring as a consequence of surgical procedures and trauma can impact young patients socially and emotionally. Recently follicular unit extraction (FUE) hair transplantation has been applied to scar treatment. PATIENTS AND METHODS: This report included four patients with scarring alopecia. All patients were female with a mean age of 12.5 years. Previous operations that caused scarring were sebaceous nevus excision with direct closure (n = 2), an extensive burn scar treated using an expander (n = 1) and cauterization for a congenital pigmented nevus (n = 1). The average size of the affected area was 10.5 cm2 . The FUE transplantation procedure was performed under local anesthesia. The number of grafts was set at approximately 25-30 grafts/ cm2 of scar. An electronic punch with a diameter of 0.8 mm was used for graft harvesting, and a 0.6-mm electronic punch was used to make cylindrical holes on recipient site. The donor sites were shaved followed by graft harvesting in two cases. For the other two cases, harvesting was done without shaving. RESULTS: The number of transplanted grafts was 60 to 600 (mean 288), and surgical time was 38 to 220 minutes (mean 108). The average dose of lidocaine was 1.4 mg/kg. The average survival rate of the grafts was 85%. CONCLUSION: Our experience in these cases suggests that this technique may be a viable option for the treatment of certain causes of scarring alopecia in the pediatric age group.

Comparison of the Biomechanical Stiffness of Titanium and Sonic Weld RX Osteofixation Systems for Monoblock Zygomaticomaxillary Complex Fractures.

ABSTRACT: Resorbable osteosynthesis systems are widely used for the fixation of zygomaticomaxillary complex (ZMC) fractures instead of titanium systems, because they do not have postoperative hardware-related complications. However, the strength of conventional resorbable systems is inferior to that of titanium systems. Recently, ultrasound-aided resorbable osteosynthesis systems, which have higher fixation than conventional resorbable osteosynthesis systems, have become available.The purpose of this study was to compare the mechanical stiffness of the ultrasound-aided resorbable and titanium osteosynthesis systems in a cadaveric monoblock ZMC fracture model. Three human cadaveric monoblock ZMC fracture models (6 zygomas) were created. The fixation materials included the titanium (Level One Fixation; KLS Martin, Germany) and ultrasound-aided resorbable osteofixation systems (SonicWeld RX; KLS Martin). The fixation methods included the 3-point (zygomaticofrontal [ZF], zygomaticomaxillary buttress, and inferior orbital rim [Group I]) and the 2-point (ZF + inferior orbital rim [Group IIa] and ZF + zygomaticomaxillary buttress [Group IIb]) fixations. Each fixation model was mechanically tested with a load of up to 100 N, based on the previously reported postoperative masseter muscle strength, and the stiffness was calculated. Titanium was found to be stiffer than SonicWeld RX, though not significantly different. The fixation points in decreasing order of stiffness were Group I, Group IIa, and Group IIb, though the differences were not significant. In conclusion, the 2-point fixation, including the ZF fixation with SonicWeld RX, can be used as an alternative to the 3-point titanium fixation, which is considered to be stronger and stiffer.

Functional reconstruction of total upper eyelid defects with a composite radial forearm-palmaris longus tenocutaneous free flap: A report of two cases.

This report presents reconstruction of wide- and full-thickness upper eyelid defects with a composite radial forearm-splitting palmaris longus tendon flap, which maintains eyelid opening and closing functions and supporting tissue in a Meibomian gland carcinoma in the right upper eyelid (case 1) and Merkel cell carcinoma in the right upper eyelid (case 2). After tumor resection with excisional margins, the defects involved the muscle, tarsal, and mucosa, with defect sizes of 60 × 40 mm and 85 × 40 mm, respectively. A radial forearm flap with the palmaris longus tendon was transferred. The tendon was split into two strips: the upper strip was fixed to the frontal muscles for the opening function and the lower strip to the medial palpebral ligament and orbicularis oculi muscle to maintain the closing function. Flap vessels were anastomosed to the superficial temporal artery and vein through the subdermal tunnel. Postoperative courses were uneventful. At the 5-year (case 1) and 4-year (case 2) follow-up periods, there were no tumor recurrence and keratalgia, and the eyelid opening and closing functions were maintained. This approach may contribute to achievement of not only the opening function but also the closing function of the reconstructed eyelid.

Microsurgical mandibular reconstruction using a resin surgical guide combined with a metal reconstructive plate.

INTRODUCTION: In mandibular reconstruction, repositioning the mandibular position is still challenging and time consuming. We invented a new re-positioning technique using a resin plate combined with a reconstructive plate in reconstructing the mandible with an osteocutaneous free flap. The purpose of this report is to introduce this technique and evaluate the accuracy of mandibular reconstruction using free flaps. We hypothesized that this technique is precise and can reduce intraoperative plate bending at a low cost and short preparation period. METHODS: Mandibular reconstruction was successfully performed in a total of 10 cases without any complications. In this technique, a pre-bent reconstructive plate was prepared in accordance with a three-dimensional model, and then coated with resin. Intraoperatively, the mandibles were secured by fitting these plates snugly and fixing them using a reconstructive plate. Then the resin was removed and free osteocutaneous free flaps were transfer to the defect. Ten patients with a mean age of 68.2 who underwent mandibular resection for aggressive benign (n = 1) or malignant disease (n = 9) were reconstructed using this technique. Seven cases were reconstructed using fibular osteocutaneous free flaps, while scapular osteocutaneous free flaps were used in the remaining cases. The resections entailed: unilateral symphysis and lateral body in four cases, angle to ipsilateral angle in two, ramus to symphysis in two, and lateral body plus angle to symphysis in one case. The deviation of the mandible was evaluated by measuring the preoperative versus postoperative differences in the distances between six bilateral landmarks. RESULTS: There were no complications and flap failure in any of the 10 cases. No further intraoperative plate bending was required. One case underwent additional mucosal resection due to recurrence of cancer. Three cases were referred to postoperative chemoradiotherapy. Two patients expired during follow-up due to recurrence of cancer. Six cases were put back on a normal diet. The other cases who lacked opposing teeth had to remain on a soft diet. The mean follow-up period was 46.2 months. The average of the absolute deviation values was 1.45 mm. This value was 0.94 mm in six cases with mandibular body defects and 2.26 mm in four cases with mandibular defects involving the ramus. CONCLUSIONS: The present novel technique is simple, quick to prepare, and accurate. This technique can be a viable option for microsurgical mandibular reconstruction.

Application of free serratus anterior fascial flap for reconstruction of ear deformity due to hemifacial microsomia: A report of two cases.

Reconstructing congenital auricular defects due to hemifacial microsomia (HFM) is often required to deal with low hairline and defects of the temporal fascia/muscular systems. In this report, we present two cases of HFM patients (16-year-old and 20-year-old) with positional anomaly of the remnant lobule and 95% low hairline, who were treated with serratus anterior fascial flap (SFF) at the second stage of auricular construction. At the first stage, 3D costal cartilage framework was placed following the removal of hair-bearing skin, and was resurfaced with the pericranial flap. At the second stage, ear elevation was performed with cartilage block grafting, then the free SFF was used to construct cephaloauricular sulcus because of local fascial defect. The pedicles of SFF, subscapular vessels were anastomosed to the cervical vessels. No complications developed during the follow-up period of 4 years in both cases and projections of the constructed ears were satisfactorily maintained. The free SFF is naturally thin and flexible with sufficient circulation and it may be an alternative to temporo-parietal fascia flap in complicated microtia construction in HFM. © 2016 Wiley Periodicals, Inc. Microsurgery 37:436-441, 2017.

Reconstruction of the dynamic velopharyngeal function by combined radial forearm-palmaris longus tenocutaneous free flap, and superiorly based pharyngeal flap in postoncologic total palatal defect.

We attempted to reconstruct dynamic palatal function using a radial forearm-palmaris longus tenocutaneous free flap in conjunction with a pharyngeal flap for a postoncologic total-palate defect in a 67-year-old male patient. This reconstruction involved 3 important tasks, namely, separating the oral and nasal cavities, preserving the velopharyngeal space to avoid sleep apnea, and maintaining velopharyngeal closure to avoid nasal regurgitation during swallowing. In our technique, the radial forearm flap separates the oral and nasal cavities with an open rhinopharyngeal space, and a superiorly based pharyngeal flap, which is sutured to the posterior end of the forearm flap, limits the rhinopharyngeal space, and forms the bilateral velopharyngeal port. Furthermore, the palmaris longus tendon, which is attached to the forearm flap, is secured to the superior constrictor muscle to create a horizontal muscle sling. Contraction of the superior constrictor muscle leads to shrinkage of the sling, resulting in velopharyngeal closure. Swallowing therapy was started 4 weeks after the surgery. The patient could resume oral intake without any difficulties 6 months after the surgery. Speech intelligibility changed from severe to minimal hypernasality.

Preparatory intravascular stenting technique: an easier method of supermicrosurgical lymphaticovenular anastomosis.

Recent supermicrosurgical techniques have made it possible to anastomose lymph vessels to the subdermal venular system. However, because the lymphatic fluid is clear and the vessel is translucent, soft, and fragile, with a thinner wall than blood vessels, supermicrosurgical lymphaticovenular anastomosis is a demanding technique. One difficulty of lymphaticovenular anastomosis is identification of the lumen to pass the suture into it. This report describes a preparatory intravascular stenting technique to identify the lumen and perform lymphaticovenular anastomosis accurately. In this technique, we placed 9-0 or 10-0 nylon thread into the lymphatic lumen before transecting the lymph vessel. The end of the nylon was pushed through to appear from the lymphatic lumen, then advanced into the vein to stabilize the 2 vessels. This technique allows supermicrosurgical lymphaticovenular anastomosis to be performed quickly and efficiently.

Abdominal Wall Incisional Hernia Repair with the Anterior Component Separation Technique and Reinforcement with an Anterior Rectus Abdominis Sheath Flap.

Mesh repair is currently the mainstay of treatment for abdominal wall incisional hernias and is considered the standard of care. However, if radiotherapy is used, the possibility of complications such as exposure or infection of the prosthesis after the surgery as a complication of the radiotherapy is a concern. The patient was a 51-year-old woman who underwent laparotomy by a mid-abdominal incision for ovarian tumors. Approximately 2 years later, the patient presented with a hypertrophic scar of the wound and mild pain in the scar. The hypertrophic scar was improved gradually by corticosteroid injection. However, she had a bulge on the left side of the umbilicus just below the hypertrophic scar. Computed tomography showed a 65 × 69 mm2 hernial orifice on the left side of the umbilical abdominal wall, and an abdominal wall incisional hernia was diagnosed. The patient underwent closure by the ACS technique and reinforcement by unilateral inversion of the anterior rectus abdominis sheath for the abdominal wall incisional hernia. No recurrence of the hypertrophic scar or abdominal wall incisional hernia was observed during the follow-up period. In the present case, the hernial orifice was closed by a modified ACS technique that was combined with the anterior rectus abdominis sheath turnover flap. This technique is likely a less invasive and relatively simple method resulting in a tighter repair of the abdominal hernia than the ACS method alone, without prostheses.

Modified Preparatory Intravascular Stenting Technique in Super-microsurgical Lymphaticovenular Anastomosis for the Treatment of Lymphedema.

Clinical studies have reported that lymphaticovenular anastomosis (LVA) is more effective for early-stage lymphedema. However, the diameter of lymphatic vessels in early-stage lymphedema is thin (only about 0.3 mm). In this article, we report a modified preparatory intravascular stenting technique (PIST) for LVA with smaller lymphatic vessels and present the results of its application for the treatment of secondary lymphedema. In this technique, a 9-0 nylon thread is inserted into the target lymphatic vessel. Then, the thread is pulled until its tip has entered the lymphatic vessel. After that, the thread is allowed to proceed into the lumen by pushing it. Finally, with the nylon in place, the lymphatic vessel is transected and the lumen is secured. In this report, we investigated the surgical time for LVA between 10 patients who underwent LVA with modified PIST (group A) and another group of 10 patients who underwent LVA without the technique (group B). Lymphatic lumen was secured at all sites where indocyanine green lymphangiography confirmed lymphatic flow. The average outer diameter of lymphatic vessels in group A and B were 0.36 mm and 0.53 mm, respectively. The average surgical time for LVA in group A was 136 minutes, which was significantly shorter than the 187 minutes in group B. Our results indicated that modified PIST can help secure the lymphatic lumen even when the lymphatic vessels are thin. As a result, this technique can significantly reduce the surgical time for this procedure.

Experimental Study of Warburg Effect in Keloid Nodules: Implication for Downregulation of miR-133b.

Background: A keloid is composed of several nodules, which are divided into two zones: the central zone (CZ; a hypoxic region) and the marginal zone (MZ; a normoxic region). Keloid nodules play a key role in energy metabolic activity for continuous growth by increasing in number and total area. In this study, we aimed to investigate the roles of the zones in the execution of the Warburg effect and identify which microRNAs regulate this phenomenon in keloid tissue. Methods: Eleven keloids from patients were used. Using immunohistochemical analysis, 179 nodules were randomly chosen from these keloids to identify glycolytic enzymes, autophagic markers, pyruvate kinase M (PKM) 1/2, and polypyrimidine tract binding protein 1 (PTBP1). Western blot and qRT-PCR tests were also performed for PKM, PTBP1, and microRNAs (miR-133b and miR-200b, c). Results: Immunohistochemical analysis showed that the expression of the autophagic (LC3, p62) and glycolytic (GLUT1, HK2) were significantly higher in the CZ than in the MZ. PKM2 expression was significantly higher than PKM1 expression in keloid nodules. Furthermore, PKM2 expression was higher in the CZ than in the MZ. However, PKM1 and PTBP1 expression levels were higher in the MZ than in the CZ. The qRT-PCR analysis showed that miR-133b-3p was moderately downregulated in the keloids compared with its expression in the normal skin tissue. Conclusions: The Warburg effect occurred individually in nodules. The MZ presented PKM2-positive fibroblasts produced by activated PTBP1. In the CZ, PKM2-positive fibroblasts produced lactate. MiR-133b-3p was predicted to control the Warburg effect in keloids.

Modified trilobed transposition flap for a distal nasal defect.

Reconstruction of a distal nasal defect is challenging due to poor skin mobility and the potential for nasal alar retraction. A trilobed flap can utilize more mobile proximal skin, increase the total rotational arc, and decrease the tension associated with flap transposition. However, the trilobed flap may not be ideal for distal nasal defects because each flap is designed using immobile skin, which may lead to flap immobility and free margin distortion. To overcome these problems, the base and tip of each flap were extended further from the pivot point than those of the conventional trilobed flap. Herein, we report the use of the modified trilobed flap to treat 15 consecutive cases of distal nasal defects that occurred from January 2013 to December 2019. The mean duration of follow-up was 15.6 months. All flaps survived completely, and satisfactory aesthetic outcomes were achieved. No complications such as wound dehiscence, nasal asymmetry, or hypertrophic scarring were observed. The modified trilobed flap is a simple and reliable treatment for distal nasal defects.

Axillary accessory breast cancer reconstructed by a thoracodorsal artery perforator flap: A case report.

INTRODUCTION: Primary accessory breast cancer is rare and most commonly occurs in the axilla. Due to its low incidence, few studies have discussed axillary reconstruction after accessory breast cancer resection. In the present report, we describe a patient who underwent axillary reconstruction with a thoracodorsal artery perforator (TAP) flap after resection, and reconstruction methods after resection of axillary accessory breast cancer are discussed based on current and previous reports. PATIENT CONCERNS: A 60-year-old woman presented with a 7-year history of a gradually growing lump in the left axilla. DIAGNOSIS: The patient was diagnosed with latent breast cancer, axillary lymph node metastasis, or carcinoma of the accessory axillary breast with axillary lymph node metastasis. INTERVENTIONS: After preoperative chemotherapy, tumor resection and axillary lymph node dissection were performed, followed by immediate axillary reconstruction using a TAP flap. The patient received postoperative adjuvant endocrine and radiation therapy (50 Gy). OUTCOMES: No recurrence or metastasis was observed for 5 years postoperatively. The reconstructed axilla was not bulky, and scar contracture was not observed, with a full range of motion of the shoulder joint. CONCLUSION: We described a patient who underwent immediate TAP flap reconstruction after resection of accessory breast cancer and axillary lymph node dissection, followed by postoperative radiation, which could cause scar contracture. The patient was followed up for more than 5 years after the operation and radiation therapy, and the appearance of the axilla and range of motion of the shoulder were good despite postoperative radiation.

Glove-shaped Foam with Negative Pressure Wound Therapy for Skin Graft Fixation on the Hand.

Tie-over bolster dressing has been the gold standard for skin graft immobilization. However, skin grafting onto the hand remains challenging. To prevent shearing of the skin, joint fixation with Kirschner wire and casting is often required. However, wire fixation through the joint can disrupt finger growth and cause joint contracture, especially in pediatric patients. So, we performed graft fixation with negative pressure wound therapy (NPWT). The use of NPWT with skin grafting has recently been reported. Previous studies have reported that NPWT can provide even pressure on irregular wounds and in highly mobile areas. However, application of NPWT in the digital region often results in air leaks. This report includes four patients who required skin grafting on the hand. All patients received skin grafts in the affected area. Graft fixation was performed with NPWT. A glove-shaped form was designed. The hand was encased on the ventral and dorsal sides and small pieces of foam were placed between the fingers. The fixation was maintained for 7 days at a pressure of -50 to -80 mmHg. None of the cases had air leak requiring reattachment of the system and graft take was successful in all cases without any complications. The NPWT "glove-shape" technique enabled maintenance of average negative pressure for all skin grafts on the hand. This technique does not require joint fixation and may help to prevent growth disturbance and joint contracture.

Lymphoscintigraphy for prediction of effect of lymphaticovenular anastomosis for treatment of secondary lower limb lymphedema.

OBJECTIVE: The outcomes of lymphaticovenular anastomosis (LVA), especially for the lower extremities, have varied. To determine the optimal patient selection for LVA, we evaluated the smooth muscle function of lymph vessels using preoperative lymphoscintigraphy images and compared the findings with the LVA outcomes. METHODS: We performed a retrospective study of 81 patients with secondary lower extremity lymphedema who had undergone LVA between 2016 and 2018. To reduce the variability in the surgeon-specific variables that can affect the outcomes of LVA, all the cases from 2016 onward were performed by only two surgeons using standardized protocols for preoperative care, surgical technique, number of anastomoses, postoperative ambulation, and compression. The outcomes were evaluated by comparing the circumferences of the pre- and postoperative limbs. The preoperative lymphoscintigraphy findings were categorized into three types according to the range of the cephalad extent of the tracer as follows: type 1, tracer extending to the thigh or groin region; type 2, tracer extending to the lower leg or knee; and type 3, tracer localized at the ankle. The quantitative outcomes were evaluated by measuring the circumferences of the ankle, mid-calf, knee, and thigh. RESULTS: The average percentage in the reduction in the ankle, mid-calf, knee, and thigh circumference was 7.9%, 4.7%, 2.9%, and 3.0%, respectively. The average percentage in the reduction in the circumference for types 1 and 3 at the ankle, mid-calf, knee, and thigh was 11.6% and 8.6%, 7.6% and 1.6%, 5.2% and -0.5%, and 5.4% and -1.2%, respectively, with significant differences between types 1 and 3 in the thigh. The percentage of types 1, 2 and 3 was 60% to 76.4%, 11.7% to 20%, and 0% to 5.5% of the treated limbs that were similar in size to the contralateral healthy limb at the four sites of measurement, respectively. CONCLUSIONS: The use of LVA can effectively reduce the circumference of the lower limb. Our results suggest that the lymphoscintigraphy findings could help to predict the effect of LVA and could facilitate optimal patient selection.

Quantitative Morphologic Analysis of Cranial Vault in Twist1+/- Mice: Implications in Craniosynostosis.

BACKGROUND: The haploinsufficiency in the TWIST1 gene encoding a basic helix-loop-helix transcription factor is a cause of one of the craniosynostosis syndromes, Saethre-Chotzen syndrome. Patients with craniosynostosis usually require operative release of affected sutures, which makes it difficult to observe the long-term consequence of suture fusion on craniofacial growth. METHODS: In this study, we performed quantitative analysis of morphologic changes of the skull in Twist1 heterozygously-deleted mice (Twist1+/-) with micro-computed tomographic images. RESULTS: In Twist1+/- mice, fusion of the coronal suture began before postnatal day 14 and progressed until postnatal day 56, during which morphologic changes occurred. The growth of the skull was not achieved by a constant increase in the measured distances in wild type mice; some distances in the top-basal axis were decreased during the observation period. In the Twist1+/- mouse, growth in the top-basal axis was accelerated and that of the frontal cranium was reduced. In the unicoronal suture fusion mouse, the length of the zygomatic arch of affected side was shorter in the Twist1+/- mouse. In one postnatal day 56 Twist1+/- mouse with bilateral coronal suture fusion, asymmetric zygomatic arch length was identified. CONCLUSION: The authors'results suggest that measuring the length of the left and right zygomatic arches may be useful for early diagnosis of coronal suture fusion and for estimation of the timing of synostosis, and that more detailed study on the growth pattern of the normal and the synostosed skull could provide prediction of the risk of resynostosis. CLINICAL RELEVANCE STATEMENT: The data from this study can be useful to better understand the cranial growth pattern in patients with craniosynostosis.