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.

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.

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.

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.

Hypothyroidism After Using Superior Thyroid Artery as A Recipient Artery.

OBJECTIVE: Superior thyroid artery (SThA) is a common recipient artery in free tissue transfer even after total pharyngolaryngoesophagectomy (TPLE) with hemithyroidectomy. The aim of this study was to evaluate whether the use of SThA as a recipient vessel affect thyroid function in patients undergoing TPLE with hemithyroidectomy. METHODS: From 2011 to 2020, 91 patients who underwent free jejunum transfer after TPLE with hemithyroidectomy were divided into two groups. In Group1 (n = 47), the contralateral SThA was used for the anastomosis. In Group2 (n = 44), other vessels were used. Retrospective chart review was performed comparing postoperative thyroid function between two groups. RESULTS: In group1, 17 patients presented hypothyroidism, 21 presented latent hypothyroidism and 9 presented no thyroid dysfunction comparing 15, 19, and 10 respectively in group 2. There were no significant differences between the two groups. CONCLUSION: Even after hemithyroidectomy, with inferior thyroid arteries are preserved, the SThA can be used as a recipient vessel. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:557-561, 2023.

Artificial PGA/Collagen-based Bilayer Conduit in Short Gap Interposition Setting Provides Comparable Regenerative Potential to Direct Suture.

The aim of this study was to evaluate whether the Nerbridge, an artificial polyglycolic acid conduit with collagen matrix, is comparable to direct nerve suture in a rat sciatic nerve injury model in a short-gap interposition (SGI) setting. Methods: Sixty-six female Lewis rats were randomly divided into the sham group (n = 13); no reconstruction (no-recon) group (n = 13; rat model with 10 mm sciatic nerve defect); direct group (n = 20; rat sciatic nerve injury directly connected by 10-0 Nylon); and SGI group (n = 20; sciatic nerve injury repaired using 5-mm Nerbridge). Motor function and histological recovery were evaluated. The sciatic nerve and gastrocnemius muscle were harvested for quantification of the degree of nerve regeneration and muscle atrophy. Results: The SGI and direct groups achieved equal recovery in both functional and histological outcomes. At weeks 3 and 8 postsurgery, there was a significant improvement in the sciatic functional index of the SGI group when compared with that of the no-recon group (P < 0.05). Furthermore, the direct and SGI groups had less muscle atrophy at 4 and 8 weeks postsurgery compared with the no-recon group (P < 0.05). The axon density and diameter at the distal site in the SGI group were significantly higher than that in the no-recon group and comparable to that in the direct and sham groups. Conclusion: An artificial nerve conduit has equal potential as direct suture in motor nerve reconstruction when used in the SGI setting.

Peptide Receptor Radionuclide Therapy for Recurrent Olfactory Neuroblastoma After Cranioplasty for Surgical Infection: A Case Report.

BACKGROUND: Peputide receptor radionuclide therapy with 177Lu for midgut neuroendocrine metastasis has been clinically approved as a safe treatment. Unresectable metastases of olfactory neuroblastoma have shorter survival due to insufficient effective systemic treatment. CASE REPORT: Herein, we report a patient treated with peputide receptor radionuclide therapy for unresectable recurrent olfactory neusroblastoma following a rare cranial metastasectomy infection. A 50-year-old female patient with olfactory neuroblastoma of Kadish C was initially treated by skull base surgery plus postoperative radiotherapy following chemotherapy. Recurrent disease with neck and intracranial metastases was treated by four salvage surgeries. Surgical site infection following intracranial metastasectomy was treated with debridement and delayed cranioplasty. Peputide receptor radionuclide therapy was performed for unresectable multiple metastases after cranioplasty. Successful therapy using four cycles of peputide receptor radionuclide had neither grade 3 nor grade 4 adverse events. The patient was followed at an outpatient clinic. CONCLUSION: Further case accrual of peputide receptor radionuclide therapy is required to develop a treatment for unresectable olfactory neuroblastoma.

Creating and Transferring an Innervated, Vascularized Muscle Flap Made from an Elastic, Cellularized Tissue Construct Developed In Situ.

Reanimating facial structures following paralysis and muscle loss is a surgical objective that would benefit from improved options for harvesting appropriately sized muscle flaps. The objective of this study is to apply electrohydrodynamic processing to generate a cellularized, elastic, biocomposite scaffold that could develop and mature as muscle in a prepared donor site in vivo, and then be transferred as a thin muscle flap with a vascular and neural pedicle. First, an effective extracellular matrix (ECM) gel type is selected for the biocomposite scaffold from three types of ECM combined with poly(ester urethane)urea microfibers and evaluated in rat abdominal wall defects. Next, two types of precursor cells (muscle-derived and adipose-derived) are compared in constructs placed in rat hind limb defects for muscle regeneration capacity. Finally, with a construct made from dermal ECM and muscle-derived stem cells, protoflaps are implanted in one hindlimb for development and then microsurgically transferred as a free flap to the contralateral limb where stimulated muscle function is confirmed. This construct generation and in vivo incubation procedure may allow the generation of small-scale muscle flaps appropriate for transfer to the face, offering a new strategy for facial reanimation.

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

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

Placement of an elastic biodegradable cardiac patch on a subacute infarcted heart leads to cellularization with early developmental cardiomyocyte characteristics.

BACKGROUND: Placement of an elastic biodegradable patch onto a subacute myocardial infarct (MI) provides temporary elastic support that may act to effectively alter adverse left ventricular (LV) remodeling processes. METHODS: Two weeks after permanent left coronary ligation in Lewis rats, the infarcted anterior wall was covered with polyester urethane urea (MI + PEUU; n = 15) or expanded polytetrafluoroethylene (MI + ePTFE; n = 15) patches, or had no implantation (MI + sham; n = 12). Eight weeks after surgery, cardiac function and histology were assessed. RESULTS: The ventricular wall in the MI + ePTFE and MI + sham groups was composed of fibrous tissue, whereas PEUU implantation induced α-smooth muscle actin-positive muscle bundles coexpressing sarcomeric α-actinin and cardiac-specific troponin-T. This pattern of colocalization was also found in developing embryonic myocardium. Cardiac transcription factors Nkx-2.5 and GATA-4 were strongly expressed in the muscle bundles. In the MI + sham group, end-diastolic LV cavity area (EDA) increased and the percentage of fractional area change (%FAC) decreased. For ePTFE patched animals, both EDA and %FAC decreased. In contrast, with MI + PEUU patching, %FAC increased and EDA was maintained. With dobutamine-stress echocardiography, MI + PEUU patched LVs possessed contractile reserve significantly larger than the MI + sham group. CONCLUSIONS: MI + PEUU patch implantation onto subacute infarcted myocardium induced muscle cellularization with characteristics of early developmental cardiomyocytes as well as providing a functional reserve.

Upper thoracic empyema and concomitant superior vena cava syndrome treated with reconstructive surgery using a pedicled omental flap.

Superior vena cava (SVC) syndrome refers to a constellation of symptoms secondary to obstruction of blood flow through the SVC. In this condition, venous blood that usually drains into the SVC is diverted into the inferior vena cava (IVC) via collateral veins. Reconstructive surgery is challenging in such cases owing to the anomalous venous system. In this case report, we describe reconstructive surgery using a pedicled omental flap in a patient with upper thoracic empyema and concomitant SVC syndrome. A 68-year-old man underwent resection of malignant thymoma, the bilateral brachiocephalic veins, and a part of the right upper lobe, followed by polytetrafluoroethylene (PTFE) graft placement for venous system reconstruction, 2 years prior to presentation. He developed postoperative upper thoracic cavity empyema, which necessitated PTFE graft removal. Although the infection was controlled after 2 months, multiple right upper lobe pulmonary fistulas persisted, and the patient was referred to our department for further evaluation. Contrast-enhanced computed tomography revealed SVC syndrome characterized by SVC obstruction and consequent drainage of venous blood from the upper trunk into the IVC via collateral vessels. We debrided necrotic and infected tissues, and a pedicled omental flap was placed for upper lobe fistula coverage. The patient showed an uncomplicated postoperative course, and no recurrent empyema or pulmonary fistulas were observed 3 years postoperatively. Flaps associated with the SVC system show high venous pressures. The use of a pedicled omental flap was deemed feasible because this graft reaches the upper thorax even though it is associated with the IVC system.

Effect of Incision Negative Pressure Wound Therapy on Donor Site Morbidity in Breast Reconstruction with Deep Inferior Epigastric Artery Perforator Flap.

Background: The usefulness of closed incision negative pressure wound therapy (ciNPWT) has been well documented in many surgical sites, except for the donor site of the deep inferior epigastric artery perforator (DIEP) flap. The aim of this study was to evaluate the effect of ciNPWT on microsurgical breast reconstruction using a DIEP flap. Methods: Fifty-six cases of breast reconstruction with DIEP flap were included and divided into two groups based on post-surgical wound management: the ciNPWT group received ciNPWT at the donor site, while the conventional group received conventional wound management. The primary outcomes were the incidence of seroma, wound dehiscence, and surgical site infection, and secondary outcomes were the time to drain removal and amount of drainage. The breast reconstruction risk assessment (BRA) score was used to evaluate the comprehensive risk in each case. Results: Among the patient and surgical characteristics, only the BRA score (P=0.02) and the time to elevate the flap (P=0.02) were significantly higher and longer in the ciNPWT group, respectively. The incidence of seroma, dehiscence, and wound infection showed no significant difference between the two groups. In the subgroup analysis of patients with body mass index ≥ 25, the primary outcomes did not differ, while the secondary outcomes were significantly lower in the ciNPWT group (drainage volume, P = 0.04; time to drain removal, P = 0.04). Conclusion: ciNPWT can potentially reduce the incidence of donor site complications of DIEP flaps, especially if the comprehensive risk for post-surgical complications is considered.

Development of a Novel Scar Screening System with Machine Learning.

BACKGROUND: Hypertrophic scars and keloids tend to cause serious functional and cosmetic impediments to patients. As these scars are not life threatening, many patients do not seek proper treatment. Thus, educating physicians and patients regarding these scars is important. The authors aimed to develop an algorithm for a scar screening system and compare the accuracy of the system with that of physicians. This algorithm was designed to involve health care providers and patients. METHODS: Digital images were obtained from Google Images (Google LLC, Mountain View, Calif.), open access repositories, and patients in the authors' hospital. After preprocessing, 3768 images were uploaded to the Google Cloud AutoML Vision platform and labeled with one of the four diagnoses: immature scars, mature scars, hypertrophic scars, and keloid. A consensus label for each image was compared with the label provided by physicians. RESULTS: For all diagnoses, the average precision (positive predictive value) of the algorithm was 80.7 percent, the average recall (sensitivity) was 71 percent, and the area under the curve was 0.846. The algorithm afforded 77 correct diagnoses with an accuracy of 77 percent. Conversely, the average physician accuracy was 68.7 percent. The Cohen kappa coefficient of the algorithm was 0.69, while that of the physicians was 0.59. CONCLUSIONS: The authors developed a computer vision algorithm that can diagnose four scar types using automated machine learning. Future iterations of this algorithm, with more comprehensive accuracy, can be embedded in telehealth and digital imaging platforms used by patients and primary doctors. The scar screening system with machine learning may be a valuable support tool for physicians and patients. CLINICAL QUESTION/LEVEL OF EVIDENCE: Diagnostic, II.

Colon cancer with extensive invasion of the abdominal wall treated with neoadjuvant chemotherapy and a free anterolateral thigh flap.

BACKGROUND: The treatment of locally advanced colon cancer is challenging, particularly when there is invasion of the abdominal wall. In such cases, balancing the securing of margins and sufficiently repairing abdominal wall defects is important, but difficult when the extent of invasion is large. CASE PRESENTATION: A 34-year-old male was referred to our hospital with abdominal pain and diagnosed with obstructive transverse colon cancer. He had undergone ileo-sigmoid colostomy at his previous hospital. The tumor was massive and invaded the abdominal wall (maximum diameter: approximately 12 cm), and was accompanied by regional lymph node swelling. No distant metastasis was detected. We diagnosed the tumor as cT4bN2bM0 Stage IIIC locally advanced transverse colon cancer and planned neoadjuvant chemotherapy. After two courses of FOLFOXIRI (5-fluorouracil, leucovorin, oxaliplatin, and irinotecan), he developed an entero-cutaneous fistula due to tumor penetration and required emergency diverting ileostomy construction. After the procedure, contrast-enhanced computed tomography showed good tumor shrinkage. As a result, the planned chemotherapy was canceled and he underwent radical resection of the tumor. En bloc extended right hemicolectomy was performed with excision of the fistula, ensuring a sufficient margin. The post-excision defect at the anterior abdominal wall involved 11 × 16 cm of fascia and 6 × 9 cm of skin located in the middle of the abdomen. A free anterolateral thigh flap was harvested from the right thigh and vascular pedicle was anastomosed to the right gastroepiploic artery and vein. The fascia lata, which was included in the anterolateral thigh flap, was sutured onto the abdominal wall fascia as inlay fashion to reconstruct the abdominal wall defect. Histopathology revealed moderately differentiated adenocarcinoma of the colon with no tumor cells in the abdominal wall tissue [post-chemotherapeutic state, therapy effect: Grade 1b; Stage IIA (ypT3N0M0)]. All resected margins of the specimen were free from adenocarcinoma. He was discharged on postoperative day 16. CONCLUSION: We report a case of colon cancer extensively invading the abdominal wall, which was completely resected. The abdominal wall defect was reconstructed with a free anterolateral thigh flap after tumor shrinkage with neoadjuvant chemotherapy. We present an efficient strategy for managing locally advanced colon cancer with extensive abdominal wall invasion.

Free calvarial periosteum graft vascularized by an omental flap in a rat model.

Because omental flaps are useful for flap prefabrication and the cambium layer of the periosteum can be osteogenic, we examined whether calvarial periosteum grafted onto greater omentum of rats was osteogenic and suitable for a flap. Distal omentum was wrapped with calvarial periosteum and so the cambium faced the omentum. Grafted omentum was harvested at 1 to 9 days. In other rats, grafted omentum was elevated as a pedicled flap and moved to the abdominal subcutis, to be harvested later at 1 to 5 months after the initial surgery. Bone formation was evaluated histologically, histochemically, and radiographically. On day 3, osteoid had formed. From day 4, calvarial periosteum was revascularized by omentum and bone was forming. New bone was maintained after grafting to subcutis for 5 months. Thus, bone formed by periosteum on the omentum could be used to reconstruct defects of the bone.

Peripheral Nerve Regeneration Using Different Germ Layer-Derived Adult Stem Cells in the Past Decade.

Peripheral nerve injuries (PNIs) are some of the most common types of traumatic lesions affecting the nervous system. Although the peripheral nervous system has a higher regenerative ability than the central nervous system, delayed treatment is associated with disturbances in both distal sensory and functional abilities. Over the past decades, adult stem cell-based therapies for peripheral nerve injuries have drawn attention from researchers. This is because various stem cells can promote regeneration after peripheral nerve injuries by differentiating into neural-line cells, secreting various neurotrophic factors, and regulating the activity of in situ Schwann cells (SCs). This article reviewed research from the past 10 years on the role of stem cells in the repair of PNIs. We concluded that adult stem cell-based therapies promote the regeneration of PNI in various ways.