Combined Vascular Resection for Locally Advanced Perihilar Cholangiocarcinoma.

OBJECTIVE: To evaluate the efficacy and safety of combined vascular resection (VR) in advanced perihilar cholangiocarcinoma (PHC). SUMMARY OF BACKGROUND DATA: Hepatectomy combined with portal vein resection (PVR) and/or hepatic artery resection (HAR) is technically demanding but an option only for tumor eradication against PHC involving the hilar hepatic inflow vessels; however, its efficacy and safety have not been well evaluated. METHODS: Patients diagnosed with PHC during 2001-2018 were included. Patients who underwent resection were divided according to combined VR. Patients undergoing VR were subdivided according to type of VR. Postoperative outcomes and OS were compared between patient groups. RESULTS: Among the 1055 consecutive patients, 787 (75%) underwent resection (without VR: n = 484, PVR: n = 157, HAR: n = 146). The incidences of postoperative complications and mortality were 49% (without VR vs with VR, 48% vs 50%; P= 0.715) and 2.1% (without VR vs with VR, 1.2% vs 3.6%; P= 0.040), respectively. The OS of patients who underwent resection with VR (median, 30 months) was shorter than that of those who underwent resection without VR (median, 61 months; P < 0.0001); however, it was longer than that of those who did not undergo resection (median, 10 months; P < 0.0001). OS was not significantly different between those who underwent PVR and those who underwent HAR (median, 29 months vs 34 months; P = 0.517). CONCLUSION: VR salvages a large number of patients from having locally advanced PHC that is otherwise unresectable and is recommended if the hilar hepatic inflow vessels are reconstructable, providing acceptable surgical outcomes and substantial survival benefits.

Feasibility and Safety of Microvascular Anastomoses Within Previously-Dissected Neck Regions.

The selection of appropriate recipient vessels is important for the success of head and neck reconstruction. Vessels located outside of previously-dissected neck regions tend to be more frequently selected due to relative ease of preparation. However, some advantages are offered regarding dead space filling and formation by using vascular anastomoses within regions previously dissected, or reusing former free flap pedicle due to their proximity to the defect. We analyzed microsurgical anastomoses in patients requiring oral reconstruction who had previously undergone neck dissection. Contralateral vascular anastomoses were preoperatively planned in 10 cases of which 9 could be successfully performed (achievement rate, 90%). Ipsilateral side anastomoses were planned in 28 cases, with 26 anastomosed as planned (achievement rate, 92.9%). There was no statistically significant difference between the two groups. Vascular anastomosis within the scar region can be performed safely, based on preoperative planning and intraoperative judgment.

Biological characterization of adipose-derived regenerative cells used for the treatment of stress urinary incontinence.

OBJECTIVE: To assess the characteristics of adipose-derived regenerative cells, and provide supportive data explaining the mechanism of efficacy observed for the use of these cells in the treatment of stress urinary incontinence. METHODS: Adipose tissues were harvested by abdominal liposuction from healthy donors and patients with stress urinary incontinence. Adipose-derived regenerative cells were isolated from tissues using the Celution system, and assessed for their characteristics and ability to differentiate into smooth muscle cells. RESULTS: Adipose-derived regenerative cells isolated by the Celution system developed into fibroblastic colonies. Flow cytometric analysis of adipose-derived stem cell markers showed that adipose-derived regenerative cells were positive for CD34 and CD44, and negative for CD31. Immunofluorescence staining after differentiation showed that colony-forming cells were positive for alpha-smooth muscle actin, calponin and desmin, which are smooth muscle cell markers. A cytokine release assay showed that adherent cells secreted cytokines associated with angiogenesis, including vascular endothelial growth factor-A, angiopoietin-2 and placental growth factor. CONCLUSIONS: Adipose-derived regenerative cells collected by the Celution system might have clonogenic capacity and an angiogenetic function. These properties might contribute to the mechanisms through which regenerative cell therapy by periurethral injection of autologous adipose-derived regenerative cells ameliorates stress urinary incontinence.

Functional evaluation following deltoid muscle resection in patients with soft tissue sarcoma.

BACKGROUND: The present study aimed to determine functional outcomes in patients undergoing deltoid muscle resection for soft tissue sarcoma. METHODS: Between 2002 and 2014, 18 patients with soft tissue sarcoma of the shoulder who underwent wide resection including the deltoid muscle, and were followed up for more than 12 months, were retrospectively included in the study. In all, 11 patients were male and 7 were female. The median age was 59 years, median follow-up duration was 37 months. The extent of resection of deltoid muscle, with or without rotator cuff damage, reconstruction methods, adjuvant therapy, oncological outcomes, and the International Society of Limb Salvage (ISOLS) score as functional outcomes were analyzed. RESULTS: Six patients underwent total resection, and twelve underwent partial resections of deltoid muscle. The rotator cuff was resected in four patients. Soft tissue reconstruction was performed in 17 patients using a pedicled latissimus dorsi muscle flap. Two local recurrences and three distant metastases occurred during follow-up. Median overall survival was 72 months. The mean ISOLS score was 25.0 points (±4.6points). Univariate analysis revealed that there was no significant difference in ISOLS score regarding the extent of deltoid muscle resection. Multivariate analysis identified only combined resection of the rotator cuff as a significant prognostic factor for poor functional outcomes (P < 0.001). CONCLUSIONS: The extent of resection of the deltoid muscle might not affect the functional outcomes determined by ISOLS score. If the rotator cuff is resected concurrently, satisfactory functional outcomes might not be obtained.

Regenerative treatment for male stress urinary incontinence by periurethral injection of adipose-derived regenerative cells: Outcome of the ADRESU study.

OBJECTIVES: To report the outcome of the ADRESU study, a multicenter, single-arm, investigator-initiated clinical trial to confirm the efficacy and safety of regenerative treatment for male patients with stress urinary incontinence. METHODS: The participants were male patients with mild-to-moderate stress urinary incontinence persisting for >1 year after prostatectomy. Autologous adipose-derived regenerative cells were isolated using the Celution system from adipose tissue obtained by liposuction. Adipose-derived regenerative cells and mixture of adipose-derived regenerative cells with adipose tissue were transurethrally injected into the rhabdosphincter and submucosal space of the urethra, respectively. The primary end-point was the proportion of patients with improvement of the urine leakage volume at 52 weeks (or last visit within 52 weeks). Improvement of leakage volume was defined as a decrease from baseline >50% by the 24-h pad test. A total of 10 secondary end-points were set. RESULTS: A total of 45 patients satisfying the eligibility criteria were enrolled. The primary end-point was met; the proportion of patients with improvement in leakage volume at 52 weeks was 37.2% (95% confidence interval 23.0-53.3%). No serious adverse events with causal relationships to the adipose-derived regenerative cells were encountered. There was a progressive improvement in secondary end-points. In the King's Health Questionnaire, improvement of quality of life scores showed greater improvement in responders, as compared with non-responders. CONCLUSIONS: Findings from the ADRESU study suggest the efficacy and safety of regenerative treatment for male patients with mild-to-moderate stress urinary incontinence.

＜Editors' Choice＞ Effects of exosomes derived from the induced pluripotent stem cells on skin wound healing.

Recently, the effects of stem cell supernatants or exosomes, such as skin wounds, have attracted attention. However, the effects of the induced pluripotent stem (iPS) cell-derived exosomes (iPS-Exos) have not been investigated in detail. Here, we investigated the effects of iPS-Exos on skin wound healing using an animal model. We isolated iPS-Exos from the iPS cell culture media. Control exosomes were isolated from unused iPS cell culture media (M-Exos). We first observed the morphologic characteristics of the isolated exosomes and examined the expression of surface antigens. The effects of these exosomes on the migratory response and proliferation of fibroblasts were analyzed as well. Additionally, using a diabetic ulcer model, the effects of iPS-Exos and M-Exos on skin wound healing were investigated. Transmission electron microscope analysis demonstrated that the size of iPS-Exos (120 ± 25 nm) was significantly larger than that of M-Exos (≤ 100 nm). Flow cytometry analyses showed that iPS-Exos were positive for CD9, CD63, and CD81, whereas they were negative for HLA-ABC and -DR expression. The migratory ability of fibroblasts cocultured with iPS-Exos was shown to be higher than that of the cells cocultured with M-Exos, as demonstrated using scratch assay. Skin wound healing model results showed that the administration of iPS-Exos results in a faster wound closure compared with that observed in the M-Exo group. In conclusion, the results obtained here indicate that iPS-Exos may promote the migration of fibroblasts in vitro and in vivo, suggesting the possibility of using iPS-Exos for the treatment of diabetic ulcer.

Use of a pedicled omental flap to reduce inflammation and vascularize an abdominal wall patch.

BACKGROUND: Although a variety of synthetic materials have been used to reconstruct tissue defects, these materials are associated with complications such as seromas, fistulas, chronic patient discomfort, and surgical site infection. While alternative, degradable materials that facilitate tissue growth have been examined. These materials can still trigger a foreign body inflammatory response that can lead to complications and discomfort. MATERIALS AND METHODS: In this report, our objective was to determine the effect of placing a pedicled omental flap under a biodegradable, microfibrous polyurethane scaffold serving as a full-wall thickness replacement of the rat abdominal wall. It was hypothesized that the presence of the omental tissue would stimulate greater vascularization of the scaffold and act to reduce markers of elevated inflammation in the patch vicinity. For control purposes, a polydimethylsiloxane sheet was placed as a barrier between the omental tissue and the overlying microfibrous scaffold. Both groups were sacrificed 8 wk after the implantation, and immunohistological and reverse transcription polymerase chain reaction (RT-PCR) assessments were performed. RESULTS: The data showed omental tissue placement to be associated with increased vascularization, a greater local M2/M1 macrophage phenotype response, and mRNA levels reduced for inflammatory markers but increased for angiogenic and antiinflammatory factors. CONCLUSIONS: From a clinical perspective, the familiarity with utilizing omental flaps for an improved healing response and infection resistance should naturally be considered as new tissue engineering approaches that are translated to tissue beds where omental flap application is practical. This report provides data in support of this concept in a small animal model.

Design of a single-arm clinical trial of regenerative therapy by periurethral injection of adipose-derived regenerative cells for male stress urinary incontinence in Japan: the ADRESU study protocol.

BACKGROUND: Male stress urinary incontinence is a prevalent condition after radical prostatectomy. While the standard recommendation for the management of urine leakage is pelvic floor muscle training, its efficacy is still unsatisfactory. Therefore, we have focused on regenerative therapy, which consists of administering a periurethral injection of autologous regenerative cells from adipose tissue, separated using the Celution® system. Based on an interim data analysis of our exploratory study, we confirmed the efficacy and acceptable safety profile of this treatment. Accordingly, we began discussions with Japanese regulatory authorities regarding the development of this therapy in Japan. The Ministry of Health, Labour and Welfare suggested that we implement a clinical trial of a new medical device based on the Pharmaceutical Affaires Act in Japan. Next, we discussed the design of this investigator-initiated clinical trial (the ADRESU study) aimed at evaluating the efficacy and safety of this therapy, in a consultation meeting with the Pharmaceuticals and Medical Device Agency. METHODS: The ADRESU study is an open-label, multi-center, single-arm study involving a total of 45 male stress urinary incontinence patients with mild-to-moderate urine leakage persisting more than 1 year after prostatectomy, in spite of behavioral and pharmacological therapies. The primary endpoint is the rate of patients at 52 weeks with improvement of urine leakage volume defined as a reduction from baseline greater than 50% by 24-h pad test. Our specific hypothesis is that the primary endpoint result will be higher than a pre-specified threshold of 10%. DISCUSSION: The ADRESU study is the first clinical trial of regenerative treatment for stress urinary incontinence by adipose-derived regenerative cells using the Celution® system based on the Japanese Pharmaceutical Affaires Act. We will evaluate the efficacy and safety in this trial to provide an adequate basis for marketing approval with the final objective of making this novel therapy widely available for Japanese patients. TRIAL REGISTRATION: This trial was registered at the University Hospital Medical information Network Clinical Trial Registry (UMIN-CTR Unique ID: UMIN000017901 ; Registered July 1, 2015) and at ClinicalTrials.gov (ClinicalTrials.gov Identifier: NCT02529865 ; Registered August 18, 2015).

Effects of Tissue Component Volumes on Vascular Resistance in Free Flaps.

Background A successful free flap transfer is achieved, in part, by having a thorough understanding of vascular anatomy and blood flow dynamics. We previously reported that vascular resistance differs by type of free flap. To test the hypothesis that the difference reflects the proportion of tissue components within free flaps, we calculated blood flow and vascular resistance for free flaps in which we determined the volume of each tissue component. Methods Measurements and calculations were made for 40 free flap transfers performed at our hospital: 7 radial forearm flaps, 14 anterolateral thigh flaps, and 19 rectus abdominis myocutaneous flaps. Results The vascular resistance of free flaps was inversely related to the volume of each tissue component. Univariate regression analysis revealed that muscle volume correlated most closely with resistance (r = 0.881), followed by skin (r = 0.622), and fat (r = 0.577). Multiple regression analysis confirmed the relationship between combined muscle and fat volume and resistance (R2 = 0.865). Conclusions A strong inverse correlation exists between vascular resistance and combined muscle and fat tissue volume in flaps. It may be helpful to consider these relationships when making decisions regarding choice of free flap and recipient vessels.

Right hepatectomy for a detoured left hepatic artery in hilar cholangiocarcinoma-report of a rare but rational resection.

BACKGROUND: Curative hepatectomy with bile duct resection is the treatment for perihilar cholangiocarcinoma. A locally advanced tumor necessitates hepatectomy with simultaneous vascular resection, and reconstruction remains an obstacle for surgeons. Studies have focused on the variations of hepatic arteries. Nevertheless, the anatomical alignment of the portal veins, bile ducts, and hepatic arteries are equally critical in surgical planning of curative resection for advanced tumors. We have reported promising outcomes of hepatectomy with simultaneous resection and reconstruction of the hepatic artery. With respect to the type of surgery, most patients undergo left hepatectomy with right hepatic artery resection and reconstruction in contrast to right hepatectomy with left hepatic artery resection and reconstruction. We present two patients who showed detoured left hepatic arteries that were invaded by the perihilar tumors. CASE PRESENTATION: A 78-year-old man who presented with epigastric pain and abnormal liver function was referred to our clinic for further examination. Serial examination resulted in the diagnosis of Bismuth type II hilar cholangiocarcinoma. The left hepatic artery ran a detoured course and was invaded by the tumor. The second patient was a 76-year-old woman who presented with jaundice and the Bismuth type II hilar cholangiocarcinoma. The left hepatic artery was along the right-lateral position of the left portal vein and was invaded by the tumor. The variant anatomical relationship of the vessel was identified preoperatively in both patients, and they underwent right hepatectomy with concomitant left hepatic artery resection and reconstruction without any major complications or recurrence. CONCLUSIONS: The largely biased selection of patients is based on the following anatomical relationship: the left hepatic artery usually runs left lateral to the portal vein, which spares invasion by the perihilar cholangiocarcinoma. On the contrary, the right hepatic artery mostly runs behind the bile duct and is invaded by the tumor. This aforementioned anatomy is one of the reasons for the relatively rare left hepatic artery resections and reconstructions in right hepatectomies. By meticulous preoperative evaluation with images, we identify the anatomical variation and performed right hepatectomy with concomitant left hepatic artery resection and reconstruction without any major complications and mortalities.

Post-operative pulmonary and shoulder function after sternal reconstruction for patients with chest wall sarcomas.

BACKGROUND: Sternal resection is occasionally required for patients with malignant tumors, particularly sarcomas, in the sternal region. Few reports have described post-operative respiratory and shoulder function after sternal resection for patients with bone and soft-tissue sarcomas. METHODS: Eight consecutive patients with bone and soft tissue sarcomas requiring sternal resection were the focus of this study. Chest wall was reconstructed with a non-rigid or semi-rigid prosthesis combined, in most cases, with soft tissue flap reconstruction. Clinical outcomes investigated included complications, shoulder function, evaluated with Musculoskeletal Tumor Society-International Symposium of Limb Salvage system, and respiratory function, evaluated by use of spirometry. RESULTS: The anterior chest wall was reconstructed with non-rigid strings for 3 patients and with polypropylene mesh for 5. There were no severe post-operative complications, for example surgical site infection or pneumonia. All 3 patients with non-rigid reconstruction experienced paradoxical breathing, whereas none with polypropylene mesh did so. Post-operatively, FEV(1)% was unchanged but %VC was significantly reduced (p = 0.01), irrespective of the reconstruction method used (strings or polypropylene mesh). Shoulder function was not impaired. CONCLUSIONS: Among patients undergoing sternal resection, post-operative shoulder function was excellent. Pulmonary function was slightly restricted, but not sufficiently so to interfere with the activities of daily living (ADL). Paradoxical breathing is a slight concern for non-rigid reconstruction.

Salvage surgery and microsurgical reconstruction for recurrence of skull base osteosarcoma after carbon ion radiotherapy.

Carbon ion radiotherapy has recently emerged as an alternative choice of treatment for malignant tumors of the head and neck. However, it is still in the infant stages and its influence on subsequent salvage surgery remains unclear. Here we report the case of a 43-year-old woman who underwent salvage surgery for left frontal bone osteosarcoma recurrence following carbon ion radiotherapy. Tumor resection was performed with a wide margin including the tissue considered to have been damaged by carbon ion radiotherapy. The dural defect was reconstructed using a fascia lata graft and pedicled galeal pericranial flap. The soft tissue defect was reconstructed using an anterolateral thigh flap anastomosed to the ipsilateral neck interposed by the radial forearm flap. As the patient developed no postoperative wound complications, she was able to initiate adjuvant chemotherapy early. Carbon ion radiotherapy is useful for its focused distribution and strong biological effects. Although the affected field may be limited, its high potency may severely damage adjacent normal tissue and lead to serious postoperative complications. Despite these concerns, satisfactory results were achieved in this case.

Non-rigid reconstruction of chest wall defects after resection of musculoskeletal tumors.

PURPOSE: We analyzed the techniques used and the complications occurring in chest wall reconstruction after resection of musculoskeletal tumors to identify the optimal reconstruction method. METHODS: The medical records of 50 patients with primary or metastatic malignant tumors requiring chest wall full thickness resection were retrospectively reviewed. The surgical technique and rate of postoperative complications were investigated, and the factors influencing complications were identified. RESULTS: Flap transfer was used in 23 cases (46 %). For skeletal reconstruction, a prosthetic mesh was used in 19 cases. In 18 recent cases, no prosthetic mesh was used, and patients were treated using only suture stabilization. Postoperative complications were recognized in 11 cases (22 %). The analysis of factors influencing the development of complications identified the use of preoperative adjuvant chemotherapy (p < 0.05), the bone as the primary site (p < 0.05), an anterolateral location (p = 0.081) and resection of ≥ 3 ribs (p = 0.077) as significant factors. No significant difference in the rate of complications was noted between the groups divided based on whether mesh was used. CONCLUSION: We used non-rigid reconstruction for full thickness resection of the chest wall, and achieved good postoperative outcomes with no grade 4 complications or perioperative mortality. Non-rigid reconstruction using flap transfers and careful respiratory management is a useful method for treating patients requiring chest wall full thickness resection.

Immunomodulatory effects of the pentapeptide YGSRS on human peripheral-blood mononuclear cells.

CONTEXT: The pentapeptide YGSRS is originated from coffee bean, while its pharmacological features have little been examined. OBJECTIVES: We investigated the effects of YGSRS on proliferation, cytokine production and CD4+ CD25+ Foxp3+ regulatory T (Treg) cell frequency of human peripheral blood mononuclear cells (PBMCs) activated by T-cell mitogen. MATERIALS AND METHODS: The effects of YGSRS on T-cell mitogen-activated PBMCs were assessed by WST assay procedures. Concentrations of Th1/Th2/Th17 cytokines in the PBMCs culture medium were analyzed with beads-array procedures followed by analysis with flow cytometry. The CD4+ CD25+ Foxp3+ Treg cells in mitogen-activated PBMCs were stained with fluorescence-labeled specific antibodies followed by flow cytometry. RESULTS: YGSRS at 1-10,000 ng/ml (1.56-15,600 nM) has a tendency to promote the mitogen-activated proliferation of PBMCs, but the effects were not statistically significant. YGSRS affect the production of tumor necrosis factor (TNF) α, interleukin (IL)-4, IL-6 and IL-10 from the activated PBMCs, and statistically significant increase in the concentrations of IL-6 and IL-10 in the medium were observed at 1-1000 ng/ml (1.56-1560 nM) (p < 0.05). YGSRS has a tendency to decrease the frequency of Treg cells in the activated PBMCs, but the difference was not statistically significant. DISCUSSION AND CONCLUSIONS: The data suggest that the pentapeptide YGSRS affects the production of several types of cytokines from activated human peripheral T cells, which may modulate Th2 type immunity.

Skin-derived precursor cells promote wound healing in diabetic mice.

BACKGROUND: Impaired wound healing as one of the complications arising from diabetes mellitus is a serious clinical issue. Recently, various cell therapies have been reported for promotion of wound healing. Skin-derived precursor cells (SKPs) are multipotent adult stem cells with the tendency to differentiate into neurons. We investigated the potency of promoting diabetic wound healing by the application of SKPs. METHODS: Skin-derived precursor cells isolated from diabetic murine skin were cultured in sphere formation medium. At passage 2, they were suspended in phosphate-buffered saline (PBS), and applied topically to full-thickness excisional cutaneous wounds in diabetic mice. Application of PBS served as controls (n = 21 for each group; n = 42 total). Time to closure and percentage closure were calculated by morphometry. Wounds were harvested at 10 and 28 days and then processed, sectioned, and stained (CD31, α-smooth muscle actin, and neurofilament heavy chain) to quantify vascularity and neurofilaments. RESULTS: Wounds treated with SKPs demonstrated a significantly decreased time to closure (18.63 days) compared with PBS-control wounds (21.72 days, P < 0.01), and a significant improvement in percentage closure at 7, 10, 14, and 18 days compared with PBS-control wounds (P < 0.01). Histological analysis showed that the Capillary Score (the number of vessels/mm2) was significantly higher in SKP-treated wounds at day 10 but not at day 28. Nerve Density (the number of neurofilaments/mm2) had increased significantly in SKP-treated wounds at day 28 compared with control group. Some applied SKPs were stained by neurofilament heavy chain, which demonstrates that SKPs directly differentiated into neurons. CONCLUSIONS: Skin-derived precursor cells promoted diabetic wound healings through vasculogenesis at the early stage of wound healing. Skin-derived precursor cells are a possible therapeutic tool for diabetic impaired wound healing.

Regenerative treatment of male stress urinary incontinence by periurethral injection of autologous adipose-derived regenerative cells: 1-year outcomes in 11 patients.

OBJECTIVES: To assess the efficacy and safety of a novel cell therapy for male stress urinary incontinence consisting of periurethral injection of autologous adipose-derived regenerative cells, and to determine the 1-year outcomes. METHODS: A total of 11 male patients with persistent stress urinary incontinence after prostate surgery were included in the study. The Celution system was used to isolate adipose-derived regenerative cells from abdominal adipose tissue obtained by liposuction. Subsequently, these regenerative cells, and a mixture of regenerative cells and adipose tissue were transurethrally injected into the rhabdosphincter and submucosal space of the urethra, respectively. The 1-year outcomes were assessed using a 24-h pad test, a validated patient questionnaire, urethral pressure profile, transrectal ultrasonography and magnetic resonance imaging. RESULTS: Stress urinary incontinence improved progressively in eight patients during the 1-year follow up, as determined by a 59.8% decrease in the leakage volume in the 24-h pad test, decreased frequency and amount of incontinence, and improved quality of life. One patient achieved total continence. The mean maximum urethral closing pressure and functional profile length increased from 35.5 to 44.7 cmH2O, and from 20.4 to 26.0 mm, respectively. Magnetic resonance imaging showed the sustained presence of the injected adipose tissue, and enhanced ultrasonography showed a progressive increase in blood flow to the injected area in all patients. No significant adverse events were observed peri- or postoperatively. CONCLUSION: Periurethral injection of autologous adipose-derived regenerative cells might represent a safe and feasible treatment modality for male stress urinary incontinence.

Surgical correction of microstomia in a patient with antilaminin 332 mucous membrane pemphigoid.

Microstomia is a term used to describe a small oral aperture. Most of the reported cases are caused by scar contracture after facial trauma, burn injury, and tumor excision. We experienced a rare case of microstomia in a patient with antilaminin 332 mucous membrane pemphigoid, which was an acquired autoimmune disease and showed blisters and erosive lesions mainly on the mucous membranes. The patient had recurrent aphthous stomatitis and presented microstomia caused by scar contracture of oral mucosa. We surgically corrected microstomia by 5-flap Z-plasty for commissuroplasty and 2 Z-plasty of both upper and lower lips for an enlargement of oral aperture. The patient could achieve an enough oral aperture and was satisfied with the result. There was no recurrence of microstomia for 2 years.

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.

Negative pressure wound therapy for a large skin ulcer following repair of huge myeloschisis with kyphosis in a newborn.

BACKGROUND: In surgery of repair for spina bifida, various skin plastic techniques are sometimes necessary due to large skin defect or subsequent ulcers in cases when approximation on the midline is difficult. CASE REPORT: A baby was born with a large skin defect due to huge lumbar myeloschisis and kyphosis, which was repaired 2 days after birth using Limberg's skin flap at the peak of kyphosis. Skin ischemia around the tip of the flap gradually enlarged and resulted in a large skin ulcer. We performed negative pressure wound therapy (NPWT) using a Vacuum Assisted Closure (V.A.C.®) therapy system for 4 weeks which shrank the ulcer remarkably. Subsequently, a pedicle skin flap without graft was performed to cover the rest of the ulcer, which adapted well without CSF leakage postoperatively. CONCLUSION: A combination treatment of NPWT and skin plastic surgery was successfully performed for a very young infant with spina bifida. NPWT could be another useful option for the treatment of ulcer following spina bifida repair surgery, though surgeons should carefully confirm that there is no CSF leakage before and during the procedure.

Long follow-up of cranofacial cleft treated by the folded vascularized calvarial bone.

Craniofacial clefts are relatively rare. Tessier proposed a classification of craniofacial clefts. A Tessier no. 10 cranial facial defect is very rare. There are few reports regarding the reconstruction of the orbital rim and roof of a Tessier number 10 cleft. In this paper, we present the reconstruction of the orbital rim and roof by a folded vascularized calvarial bone and the long-term follow-up results.