Pain-relieving Effects of Autologous Fat Grafting in Breast Cancer Surgery: A Scoping Review.

Background: Chronic pain is relatively common after breast cancer surgery, including breast reconstruction. Autologous fat grafting (AFG) has gained attention as a novel method for breast reconstruction, and recent clinical studies have also shown effects of AFG on alleviation of chronic pain after breast cancer surgery. Our objective was to conduct a scoping review of studies that have examined these effects with clearly defined clinical outcomes. Methods: A literature search was conducted using three databases: PubMed, MEDLINE, and Google Scholar, following PRISMA guidelines and the Arkesy and O'Malley framework. The search focused on clinical studies of the effects of AFG on chronic pain after breast cancer surgery. All studies reporting functional outcomes, return to work, and secondary surgery in a repeat operation were identified. Results: Of the 148 studies identified in the search, 11 studies with a total of 684 patients were included in the review. The average volume of fat grafted was approximately 128 mL over an average of 1.6 sessions. The most common time point for assessment was 1 year post-AFG. In all studies with an evidence level of 3 or lower, AFG showed positive results in alleviating pain after breast cancer surgery. However, one of the three randomized controlled trials did not show clinically significant effects. Conclusions: Most of the studies examined in this review suggested pain-relieving effects of AFG. However, there was one randomized controlled trial in which these effects were not confirmed, indicating a need for further accumulation of cases and performance of new, well-designed randomized controlled trials.

A novel surgical correction using a combination of wave-like incision and Z-axis Z-plasty for congenital constriction band syndrome.

BACKGROUND: A congenital constriction band (CCB) is a relatively common anomaly among limb malformations. However, the number of cases treated at a given center is limited and differences in techniques used by surgeons at each facility have a significant impact on the treatment outcomes. Several surgical methods have been reported, but a standard technique that yields consistent satisfactory results is still needed. Here, we introduce a novel technique for the treatment of CCB syndrome that uses a combination of wave-like skin incision and Z-axis Z-plasty. PATIENTS AND METHODS: A wave-like incision was used for skin incision with the goals of achieving an accordion effect and a less noticeable post-operative scar. After the fibrous constriction band was completely excised, a Z-plasty of sufficient size in the Z-axis direction was performed on the dermis-inclusive adipose tissue. For over 10 years, this technique was applied to 11 sites in 6 patients. A retrospective study of the characteristics of these cases was performed, including age at surgery, gender, type of deformity, degree of constriction, types of examination, number of surgeries, and post-operative outcomes. RESULTS: In all patients, a normal contour of the limbs was achieved and the hourglass-like deformity caused by the constriction band was satisfactorily improved. No additional corrective surgeries were needed, there was no abnormal growth of the treated limbs, and scarring was aesthetically acceptable in all cases. CONCLUSION: The novel technique described here uses deep subcutaneous fat to correct the hourglass-like deformity and restores a normal limb contour, while the wave-like skin incision minimizes post-operative scarring.

Human Adipose-Derived Endothelial Progenitor Cells Accelerate Epithelialization of Radiation Ulcers in Nude Mice.

BACKGROUND: Cotransplantation of adipose-derived stem cells (ASCs) and endothelial progenitor cells has shown superior angiogenic effects compared with ASCs alone in recent animal studies. However, endothelial progenitor cells could only be collected from blood vessels or bone marrow. Thus, the authors have established a method for purifying adipose-derived endothelial progenitor cells (AEPCs). The authors hypothesized that AEPCs would enhance the therapeutic effect of ASCs on radiation ulcers. METHODS: Seven-week-old male nude mice (BALB/cAJcl-nu/nu) were irradiated on the dorsal skin (total 40 Gy); 12 weeks later, 6-mm-diameter wounds were created. The mice were then treated with subcutaneous injection of human ASCs [1 × 10 5 ( n = 4)], human AEPCs [2 × 10 5 or 5 × 10 5 ( n = 5)], combinations of those [ASCs 1 × 10 5 plus AEPCs 2 × 10 5 ( n = 4) or 5 × 10 5 ( n = 5)], or only vehicle ( n = 7). The nonirradiated group was also prepared as a control ( n = 6). The days required for macroscopic epithelialization was compared, and immunostaining for human-derived cells and vascular endothelial cells was performed at day 28. RESULTS: AEPC-ASC combination-treated groups healed faster than the ASC-treated group (14 ± 0 days versus 17 ± 2 days; P < 0.01). Engraftment of the injected cells could not be confirmed. Only the nonirradiated mice had significantly higher vascular density (0.988 ± 0.183 × 10 -5 /µm -2 versus 0.474 ± 0.092 × 10 -5 /µm 2 ; P = 0.02). CONCLUSION: The results suggested therapeutic potentials of AEPCs and an enhanced effect of combination with ASCs. This study is a xenogenic transplantation model, and further validation in an autologous transplantation model is needed. CLINICAL RELEVANCE STATEMENT: Human AEPCs and their combination with ASCs accelerated epithelialization of radiation ulcers in nude mice. The authors suggest that administration of humoral factors secreted from AEPCs (eg, treatment with culture-conditioned media) could be used for the same purpose.

An Effective Approach to Collecting Lymph Vessels Using a Small Diameter Wire for Lymphaticovenous Anastomosis in Upper Limb Lymphedema.

Lymphaticovenous anastomosis (LVA), which involves connecting lymphatic vessels to veins under a microscope, is widely performed around the world as a surgical treatment for lymphedema due to its relatively low patient burden and consistent efficacy. One of the crucial points of LVA is identifying suitable lymphatic vessels from among many lymphatic vessels and connecting them at the most effective site, but in practice, this is not easy to do. To overcome this issue, we have been able to effectively drain lymph by connecting lymphatic vessels to veins just before the occluded site using a lymphatic wire that was just recently developed in Japan. The device guides the subcutaneous deep collecting lymphatic vessels from the peripheral relatively superficial lymphatic vessels. While this special wire is typically adapted in the lower limbs, we have confirmed its effectiveness in upper limb lymphedema as well. Overall, this approach shows promise for improving the accuracy and success rates of LVA procedures, which can have significant benefits for patients with upper limb lymphedema. In this article, we share our experience using lymphatic wire for upper limb lymphedema cases.

Irradiation affects adipose-derived stem cells and wound healing depending on radiation dose and frequency.

BACKGROUND: Radiation therapies are often associated with permanent devitalization in the surrounding tissue. We hypothesized that stem cells are damaged depending on each irradiation dose and frequency of fractionated radiotherapies, which results in impaired tissue function including wound healing capacity. METHODS: To test the hypothesis, susceptibility of human adipose-derived stem cells (ASCs) to a single irradiation (0-10 Gy) was assessed in vitro. In vivo chronic radiation effects were also assessed on the mouse dorsal skin (N=4-5) for 6 months after a total of 40 Gy irradiation (0 Gy as control) using one of three fractionated protocols (2 Gy daily for 20 days, 10 Gy weekly for 4 weeks, or 10 Gy monthly for 4 months). Oxygen partial pressure, oxygen saturation of hemoglobin, and dorsal skin viscoelasticity were periodically measured, and wound healing and tissue immunohistology were compared at 6 months. RESULTS: A single irradiation of cultured human ASCs resulted in a dose-dependent increase in cell death up to 2 Gy but with no further increases between 2 and 10 Gy. Most of the apoptotic ASCs were in the proliferation phase. Among the three in vivo irradiation protocols, the 2 Gy×20 group had the most severe chronic tissue damage (i.e., skin dysfunction, subcutaneous atrophy, and depletion of CD34+ stem cells) 6 months after the irradiation. Wound healing was also impaired most significantly in the 2 Gy×20 group. CONCLUSIONS: These results have important clinical implications for surgeons and radiotherapists such as the timing of surgical interventions and the optimization of fractionation protocols.Clinical Relevance Statement: Irradiation damages stem cells depending on the radiation dose and frequency. Using the ultimately optimized protocol, we can minimize the long-term functional deficits of radiated tissue without losing anti-cancer efficacy of radiation therapy.

Current Fat Grafting Practices and Preferences: A Survey from Members of ISPRES.

Fat grafting has established its niche in a wide spectrum of aesthetic and reconstructive procedures. A consensus-based method of harvest, processing, enrichment, injection, and assessment is lacking, despite the rising trends in its application. We conducted a survey among plastic surgeons to evaluate and identify trends of fat grafting practices. Methods: We conducted an electronic survey with a 30-item questionnaire of 62 members of the International Society of Plastic Regenerative Surgeons. We collected demographic information, techniques, and experiences related to large volume (100-200 ml) and small-volume (<100 ml) fat grafting. Results: The majority of the respondents worked predominantly as aesthetic surgeons. The donor area selection was based on the patient's fat availability (59.7%). For fat enrichment, platelet-rich-plasma and adipose stem cells were routinely used by 12.9% and 9.7% of respondents, respectively. A 3- to 4-mm cannula with three holes was the most preferred instrument for large-volume fat harvesting (69.5%). For small-volume fat grafting, 2-mm cannulas (75.8%) with Mercedes tip (27.3%) were used most commonly. For processing, decantation of fat was performed by 56.5% of respondents (without exclusivity). For handheld injections (without exclusivity), respondents preferred a 1- to 2-mm cannula with a 1 cm3 syringe. The most popular method of outcome assessment was photographic evaluation. Conclusions: The respondents' tendencies were similar to those reported in the previous literature, with some exceptions, such as the technique for preparing fat and enrichment. A wider cross-sectional survey, involving national delegates and global representatives of plastic surgeons, is anticipated.

Prophylactic Application of Human Adipose Tissue-Derived Products to Prevent Radiation Disorders.

BACKGROUND: Radiation therapy is a mainstay treatment for malignancies, but it can induce deterministic adverse effects in surrounding healthy tissues, including atrophy, fibrosis, ischemia, and impaired wound healing. This exploratory study investigated whether prophylactic administration of products containing adipose tissue-derived stem cells immediately after radiotherapy could prevent the development of long-term functional disorders in irradiated tissues. METHODS: A total irradiation dose of 40 Gy (10 Gy, four times weekly) was delivered to the dorsal skin of nude mice. Subsequently, a prophylactic treatment with vehicle, fat tissue, stromal vascular fraction, or micronized cellular adipose matrix was injected subcutaneously into the irradiated area. Six months after these prophylactic treatments, a cutaneous punch wound was created to evaluate histologic changes and wound healing. RESULTS: Histologic assessments demonstrated dermal thickening, atrophy, and increased collagen deposits in the subcutaneous fatty layer 6 months after radiotherapy. In addition, wound healing was significantly delayed. The prophylactic treatments with three different types of human adipose tissue-derived products significantly prevented radiation-induced histologic changes and accelerated wound healing compared with the vehicle-treated irradiated group. CONCLUSIONS: This is the first study to demonstrate potential for prophylactic treatments after radiotherapy, which could prevent the progression of chronic radiation therapy disorders. The results could have a substantial impact on current anticancer radiotherapies; a next-generation radiation therapy may need to be always combined with a stem cell therapy. Such prophylactic treatments have the potential to improve wound healing of irradiated tissue and clinical outcomes of reconstructive surgery required after cancer radiotherapy. CLINICAL RELEVANCE STATEMENT: The results of this study suggest that it is clinically possible to prevent the development of radiation disorders using stem cell therapies. This study may provide a new concept of prophylactic treatment, which would be a paradigm shift in radiotherapy.

Micronized Cellular Adipose Matrix Promotes the Therapeutic Effect of an Artificial Nerve Conduit in Peripheral Nerve Gap Injury.

BACKGROUND: Stromal vascular fraction (SVF) isolated from adipose tissue has been shown to be beneficial for treating peripheral nerve injuries. Micronized cellular adipose matrix (MCAM) is an SVF-rich micronized fat tissue obtained by a series of simple mechanical processes. This study assessed the therapeutic effect of MCAM for peripheral nerve injury. METHODS: Microscopic evaluation of the cell phenotype and functions was performed to determine the adipose-derived stem cell content of the MCAM. An artificial nerve conduit (ANC) filled with MCAM was implanted into a sciatic nerve defect in immunodeficient mice. Comparisons of this treatment with an autograft, an ANC filled with SVF cells, and an ANC alone were made based on electrophysiologic characteristics, Sciatic Functional Index, and histologic analyses of regenerated nerve fiber and myelination using electron microscopy, and the preventive effect on innervated muscle atrophy. RESULTS: MCAM contained many cells with a phenotype and differentiation potency similar to those of ADSCs. The implantation experiment indicated that MCAM enhanced the efficiency of functional and structural recovery and prevented atrophy of the innervated muscle. These effects were significantly improved compared with the control group (ANC only) and comparable to those in the SVF group, whereas the improvement did not reach the same level of the autograft group. CONCLUSION: Injection of MCAM into an ANC accelerated nerve regeneration compared with use of an ANC alone, which indicates that MCAM is a promising transplant material for treatment of peripheral nerve injury and an alternative to use of SVF cells. CLINICAL RELEVANCE STATEMENT: Micronized cellular adipose matrix, which can be harvested and isolated from adipose tissue with a simple device, has been shown for the first time to be highly useful as an implantable material for new peripheral nerve regeneration.

Wearable, wireless, multi-sensor device for monitoring tissue circulation after free-tissue transplantation: a multicentre clinical trial.

Wearable sensors have seen remarkable recent technological developments, and their role in healthcare is expected to expand. Specifically, monitoring tissue circulation in patients who have undergone reconstructive surgery is critical because blood flow deficiencies must be rescued within hours or the transplant will fail due to thrombosis/haematoma within the artery or vein. We design a wearable, wireless, continuous, multipoint sensor to monitor tissue circulation. The system measures pulse waves, skin colour, and tissue temperature to reproduce physician assessment. Data are analysed in real time for patient risk using an algorithm. This multicentre clinical trial involved 73 patients who underwent transplant surgery and had their tissue circulation monitored until postoperative day 7. Herein, we show that the overall agreement rate between physician and sensor findings is 99.2%. In addition, the patient questionnaire results indicate that the device is easy to wear. The sensor demonstrates non-invasive, real-time, continuous, multi-point, wireless, and reliable monitoring for postoperative care. This wearable system can improve the success rate of reconstructive surgeries.

Asystole Due to Oculocardiac Reflex during Surgical Repair of an Orbital Blowout Fracture.

Bradycardia and asystole due to oculocardiac reflex (OCR) are potential intraoperative complications of periocular surgery. We report a case of asystole due to OCR that occurred during surgical repair performed 40 hours after an orbital blowout fracture. The patient had vomiting, bradycardia, and ocular motility disorder before the operation. During the operation, asystole occurred when the entrapped tissue was grasped with forceps. After administration of anticholinergic drugs, the heart promptly resumed beating, and no sequelae due to asystole were observed after surgery. Before and during periocular surgery, it is important for the surgeon to maintain a protective surgical procedure and communicate appropriately with the anesthesiologist, including discussion of risks and emergency measures. In addition, prolonged entrapment of the extraocular muscles is likely to cause irreversible damage, so it is important to make a diagnosis and perform surgery as soon as possible.

Metformin combined with local irradiation provokes abscopal effects in a murine rectal cancer model.

Although preoperative chemoradiation therapy can down-stage locally advanced rectal cancer (LARC), it has little effect on distant metastases. Metformin exerts an anti-cancer effect partly through the activation of host immunity. LuM1, a highly lung metastatic subclone of colon 26, was injected subcutaneously (sc) in BALB/c mice and treated with metformin and/or local radiation (RT). Lung metastases and the primary tumors were evaluated and the phenotypes of immune cells in the spleen and lung metastases were examined with flow cytometry and immunohistochemistry. Local RT, but not metformin, partially delayed the growth of sc tumor which was augmented with metformin. Lung metastases were unchanged in metformin or RT alone, but significantly reduced in the combined therapy. The ratios of splenic T cells tended to be low in the RT group, which were increased by the addition of metformin. IFN-γ production of the splenic CD4(+) and CD8(+) T cells was enhanced and CD49b (+) CD335(+) activated NK cells was increased after combined treatment group. Density of NK cells infiltrating in lung metastases was increased after combination treatment. Metformin effectively enhances local and abscopal effects of RT though the activation of cell-mediated immunity and might be clinically useful for LARC.

Genetic and cytometric analyses of subcutaneous adipose tissue in patients with hemophilia and HIV-associated lipodystrophy.

BACKGROUND: The authors recently performed plastic surgeries for a small number of patients with hemophilia, HIV infection, and morphologic evidence of lipodystrophy. Because the pathophysiological mechanism of HIV-associated lipodystrophy remains to be elucidated, we analyzed subcutaneous adipose tissues from the patients. METHODS: All six patients had previously been treated with older nucleoside analogue reverse-transcriptase inhibitors (NRTIs; stavudine, didanosine or zidovudine). Abdominal and inguinal subcutaneous fat samples were obtained from the HIV+ patients with hemophilia and HIV- healthy volunteers (n = 6 per group), and analyzed via DNA microarray, real-time PCR, flow cytometry and immunohistochemistry. RESULTS: The time from initial NRTI treatment to collecting samples were 21.7 years in average. Cytometric analysis revealed infiltration of inflammatory M1 macrophages into HIV-infected adipose tissue and depletion of adipose-derived stem cells, possibly due to exhaustion following sustained adipocyte death. Genetic analysis revealed that adipose tissue from HIV+ group had increased immune activation, mitochondrial toxicity, chronic inflammation, progressive fibrosis and adipocyte dysfunction (e.g. insulin resistance, inhibited adipocyte differentiation and accelerated apoptosis). Of note, both triglyceride synthesis and lipolysis were inhibited in adipose tissue from patients with HIV. CONCLUSIONS: Our findings provide important insights into the pathogenesis of HIV-associated lipodystrophy, suggesting that fat redistribution may critically depend on adipocytes' sensitivity to drug-induced mitochondrial toxicity, which may lead either to atrophy or metabolic complications.

Purification and characterization of human adipose-resident microvascular endothelial progenitor cells.

Human adipose tissue is a rich source of adipose-derived stem cells (ASCs) and vascular endothelial progenitor cells (EPCs). However, no standardized method has been established for the isolation and purification of adipose-derived EPCs (AEPCs). The aim of this study was to establish a method for the isolation and purification of AEPCs. The stromal vascular fraction (SVF) was extracted from human lipoaspirates, and the CD45-CD31+ fraction of the SVF was collected by magnetic-activated cell sorting (MACS). The CD45-CD31+ fraction was cultured for 4.5 days, followed by a second MACS separation to collect the CD31+ fraction. Purified AEPCs were expanded without being overwhelmed by proliferating ASCs, indicating that a high level (> 95%) of AEPC purification is a key factor for their successful isolation and expansion. AEPCs exhibited typical endothelial markers, including CD31, von Willebrand factor, and the isolectin-B4 binding capacity. AEPCs formed colonies, comparable to cultured human umbilical vein endothelial cells (HUVECs). Both AEPCs and HUVECs formed capillary-like networks in the tube formation assay, with no significant difference in network lengths. We are the first to establish a purification and expansion method to isolate these cells. Because adipose tissue is a clinically accessible and abundant tissue, AEPCs may have potential advantages as a therapeutic tool for regenerative medicine.

Adipose-Derived Stem Cell Conditioned Medium and Wound Healing: A Systematic Review.

Adipose-derived stem cells (ASCs) have been growing in popularity for their potential in wound healing and tissue engineering. Stem cell therapies are limited in application, with the need to maintain cell viability and function as well as safety concerns. It has been increasingly reported that the effects of ASCs are predominantly attributable to the paracrine effects of the secreted factors, which can be collected in conditioned medium (CM). The goal of this systematic review was to investigate the effects on wound healing of CM collected from ASC culture. Original articles relevant to ASC-CM and wound healing (in vitro: dermal fibroblast, epidermal keratinocytes, and their equivalent cell lines; in vivo: full-thickness wound models) were included. The agreement level of selections between two investigators was calculated by the kappa scores. And the information concerning to the publications, CM preparation, and its application and effects was extracted and reported in a systematic way and summarized in tables. In total, 121 publications were initially identified through a search of the PubMed/MEDLINE database with a specific search algorithm, and 36 articles were ultimately included after 2 screenings. Nineteen were in vitro studies that met the search criteria and 17 were in vivo studies with or without in vitro data. In summary, based on the included articles, treatment with ASC-CM, to a large extent, resulted in positive effects on wound healing in vitro and in vivo. Modulation of the culture conditions of ASCs producing the CM, including hypoxic conditions, alternative substrates, medium supplementation, as well as genetic modification of cells, favorably promoted the effects of ASC-CM. Finally, a discussion of the future perspectives and therapeutic potential of ASC-CM, which also addresses the limitations of the field, is presented. A limitation of the evidence is the inconsistency in CM preparation methods among included articles. In conclusion, ASC-CM is a promising novel cell-free therapy for wound healing in regenerative medicine and warrants further exploration. Impact Statement This systematic review researched in vitro and in vivo studies regarding therapeutic effects of adipose-derived stem cell (ASC) conditioned medium (CM) on wound healing, generally indicating favorable effects. ASC-CM can avoid safety concerns accompanying stem cell therapies and reduce the cost of treatment. Modulation in the process of ASC culture and CM preparation may promote its therapeutic potential. The limitation and future perspectives of the field of ASC-CM therapy were also presented. ASC-CM may be useful to its future application for a wide range of clinical targets including inflammatory and ischemic diseases.

A Novel Method of End-to-Side Microvascular Anastomosis Using T-Shaped Metal Stents: A Porcine Study.

ABSTRACT: End-to-side anastomosis requires highly specialized techniques. An easy end-to-side anastomosis technique enables anastomosis of vessels with different diameters and under various situations. We invented T-shaped metal stents and evaluated novel methods of end-to-side sutureless anastomosis, confirming their safety, effectiveness, and operability. We performed 8 end-to-side sutureless anastomoses in 4 7- to 11-month-old, male Mexican hairless piglets. After induction of anesthesia, the left femoral artery was resected by approximately 8 cm, and the superior and posterior stumps of the resected femoral artery underwent an end-to-side anastomosis with the right femoral artery by the placement of the metal stents with subsequent use of adhesive for the circumferential area. The patency of blood vessels and the presence of thrombosis were evaluated by ultrasonography or contrast-enhanced computed tomography and histology 4 weeks postoperatively. All the animals survived the procedure; no thrombosis was identified in any of the 8 anastomosis sites according to imaging studies performed 4 weeks postoperatively. Histological examination confirmed the probe patency of blood vessels and neointimal cell proliferation around stent branches. End-to-side anastomosis is possible with T-shaped metal stents. In the future, we aim for the practical application of these stents by improving their operability.

Selective Proliferation of Highly Functional Adipose-Derived Stem Cells in Microgravity Culture with Stirred Microspheres.

Therapeutic effects of adult stem-cell transplantations are limited by poor cell-retention in target organs, and a reduced potential for optimal cell differentiation compared to embryonic stem cells. However, contemporary studies have indicated heterogeneity within adult stem-cell pools, and a novel culturing technique may address these limitations by selecting those for cell proliferation which are highly functional. Here, we report the preservation of stemness in human adipose-derived stem cells (hASCs) by using microgravity conditions combined with microspheres in a stirred suspension. The cells were bound to microspheres (100-300 µm) and cultured using a wave-stirring shaker. One-week cultures using polystyrene and collagen microspheres increased the proportions of SSEA-3(+) hASCs 4.4- and 4.3-fold (2.7- and 2.9-fold increases in their numbers), respectively, compared to normal culture conditions. These cultured hASCs expressed higher levels of pluripotent markers (OCT4, SOX2, NANOG, MYC, and KLF), and had improved abilities for proliferation, colony formation, network formation, and multiple-mesenchymal differentiation. We believe that this novel culturing method may further enhance regenerative therapies using hASCs.

Multi-directional Cranial Distraction Osteogenesis for Treating Sagittal Synostosis with Frontometaphyseal Dysplasia: A Case Report.

Frontometaphyseal dysplasia (FMD), also known as Gorlin-Cohen syndrome, is a rare genetic syndrome. This syndrome affects the skeletal system and connective tissue, and causes a wide spectrum of manifestations of the skull, tubular bones, cardiovascular system, urinary system, and/or gastrointestinal system. Craniofacial findings of FMD are characterized by protruding supraorbital ridge, broad nasal bridge, hypertelorism, down-slanting palpebral fissures, and/or micrognathia. We describe a case of a 2-year-old girl diagnosed with sagittal synostosis accompanied with FMD. She presents anterior sagittal synostosis cranial form, compressed cerebrospinal fluid space (which suggested increased intracranial pressure), and the supraorbital hyperostosis. She underwent multi-directional cranial distraction osteogenesis in the calvaria and shaving of the supraorbital ridges. Despite concerns about bone fragility associated with FMD, the surgery was accomplished as usual. The patient had no intra- and postoperative complications. After 6 months of follow-up, the cranial shape has improved and the cerebrospinal fluid space has widened, but the supraorbital ridge has protruded again. Re-protrusion of the supraorbital ridge appears to be due to age-appropriate vigorous osteogenesis. The multi-directional cranial distraction osteogenesis procedure has been useful for treating sagittal synostosis even concomitant with FMD.

National survey of bladder endometriosis cases in Japan.

AIM: We aimed to describe the clinical presentation, operative or medical management, and postoperative recurrence of bladder endometriosis (BE). METHODS: We conducted a national survey to investigate BE cases from 2006 to 2016 in Japan. Histologically diagnosed cases were extracted and then investigated for the following factors: age at diagnosis, body mass index, symptoms, imaging modalities, surgical therapy, hormonal therapy, follow-up period, and postoperative recurrence. RESULTS: Eighty-nine patients with pathologically benign BE were identified. Eighty patients underwent surgery, whereas nine did not. Moreover, 34 and 44 patients underwent transurethral resection (TUR) and partial cystectomy (PC), respectively. Cumulative recurrence rates were significantly higher with TUR than with PC (p < 0.05). The recurrence rate tended to be higher after laparoscopic PC (n = 24) than after open PC (n = 20), but the difference was not statistically significant (p = 0.0879). Of the nine nonsurgical patients, eight received hormonal therapy and one did not. Efficacy rates of dienogest, GnRH agonist, and OC were 85.7%, 66.7%, and 66.7%, respectively. Of five patients with BE extending to the ureter or ureteral orifices, two underwent PC and ureteroneocystostomy and one underwent total nephroureterectomy due to renal function loss. CONCLUSION: To our knowledge, this is the first study to compare the postoperative recurrence of BE after TUR and PC. We found that cumulative recurrence rate is significantly lower after PC than after TUR. BE extending to the ureter or ureteral orifices is a very challenging condition. Further studies are required for the optimal management of BE.