Oncological safety of immediate breast reconstruction with skin- or nipple-sparing mastectomy: the value of tumor-to-dermis distance measured by preoperative ultrasonography.

BACKGROUND: Immediate breast reconstruction with skin-sparing (SSM) or nipple-sparing mastectomy (NSM) has become a common procedure. In this study, we evaluated the distance between breast tumor and skin in a series of patients undergoing IBR as it relates to oncologic safety, namely, the incidence of recurrence. METHODS: The distance of the tumor to the dermis, rather than the outer layer of skin, was the key parameter of our preoperative ultrasound measurements. Our data set comprised the cases of 171 patients and 181 breasts with breast cancer that had undergone two-stage breast reconstruction by expander. The median age of the patients was 47 years (25-75 years). The overall median follow-up period was 47.1 months (8.8-125.3 months). Eighty-five breasts underwent IBR with SSM/NSM; the others underwent conventional mastectomy. RESULTS: Among the total of 181 reconstructed breast mounds, the locoregional recurrence rate was 1.1% (2 breasts) with no cases of skin flap recurrence or skin flap necrosis. The tumor-to-dermis distance of cases with skin preservation (NSM/SSM) was significantly less than that of cases with conventional mastectomy (3.8 ± 2.7 mm vs 5.2 ± 2.4 mm). In cases with invasive carcinoma, all cases whose tumor-to-dermis distance was less than 2 mm underwent resection of the skin immediately overlying the tumor. CONCLUSIONS: Our results suggested that a 2-mm distance between the dermis and tumor on ultrasound evaluation is sufficient for the use of this tissue as a skin flap in SSM/NSM procedures. Our study indicated that immediate breast reconstruction with SSM/NSM can be an oncologically safe surgical option for breast cancer. However, we recommend that resection of the skin overlying the tumor be performed in cases with invasive breast cancer in which the tumor-to-dermis distance is less than 2 mm. TRIAL REGISTRATION: Patients in this study were retrospectively registered. This study design was approved by our Clinical Ethics Committee (No 1297) ( http://ciru.dept.showa.gunma-u.ac.jp/guidance/storage-sample/list.html ).

Evaluation of overall and disease-free survival in patients with free flaps for oral cancer resection.

PURPOSE: Sarcopenia is characterized by depletion of skeletal muscle mass (SMM) and can cause increased postoperative complication in free flap procedure. One of the most important considerations while deciding the indication of the procedure is patients' survival. This study aimed to verify the relationship between low SMM and survival in patients who undergo oral cancer resection using free flap. METHODS: SMM was evaluated using the skeletal muscle index (SMI cm2 /m2 ), which was defined using cross-sectional areas of skeletal muscles on computed tomography at the level of the third lumbar vertebrae normalized for height. Overall, 111 patients who underwent primary oral cancer resection and free flaps were included. Multivariate Cox regression analyses were used to evaluate the prognostic factors for survival. RESULTS: A total of 25 patients (22.5%) were diagnosed with low SMM. The mean SMI was 42.2 cm2 /m2 . Multivariable analyses showed that increased age (hazard ratio [HR]; 4.98, p = .004), infiltrative growth pattern INF-c (HR; 3.83, p = .037), and low SMM (HR; 2.59, p = .034) were significant negative prognostic factors for overall survival. Increased age (HR; 3.18, p = .005), extra-nodal extension (HR; 3.30, p = .001), and low SMM (HR; 2.42, p = .017) were significant negative prognostic factors for disease-free survival. CONCLUSIONS: Low SMM is a significant negative prognostic factor for overall and disease-free survival in oral cancer patients undergoing free flap. Future prospective studies are warranted to identify effective preoperative exercise and nutrition programs to improve low skeletal muscle and survival rate in patients undergoing free flap procedures.

Impact of skeletal muscle mass volume on surgical site infection in free flap reconstruction for oral cancer.

BACKGROUND: Sarcopenia is a disease in which skeletal muscle mass (SMM) and function are progressively lost. Here, we investigate surgical site infection (SSI) as a function of SMM in patients who underwent free flap reconstruction for a defect caused by oral cancer resection. METHODS: A nonrandomized, retrospective group of 122 patients treated with free flap reconstruction after oral cancer resection was enrolled in the study. All subjects also underwent preoperative abdominal-lumbar computed tomography (CT). Cross-sectional areas (cm2 ) of skeletal muscles in the L3 region were measured by manual outline on CT images. The obtained areas were normalized for height (cm2 /m2 ), and the resulting value is referred to as the skeletal muscle index (SMI). RESULTS: Recipient site SSI occurred in 30 patients (24.6%). Underweight status (body mass index [BMI] < 18.5 kg/m2 ), anemia and lower SMI were significantly related to recipient site SSI in univariate analysis (p < . 05). In multiple logistic regression analysis, lower SMI was an independent significant risk factor for recipient site SSI (p = .015, adjusted odds ratio = 1.41 per 5 cm2 /m2 decrease). CONCLUSIONS: These findings suggest that a decrease in SMM might have more impact than a decrease in BMI on SSI in free flap reconstruction after resection of oral cancer.

Pectoralis Major Pyomyositis in a Patient With Diabetes: A Case Report and Literature Review.

Pyogenic myositis is a bacterial infection of skeletal muscle that is usually caused by Staphylococcus aureus and is common in tropical regions. Recently, this infection has also been reported in immunocompromised patients in temperate regions. The lower extremities and trunk are most affected, while involvement of the chest wall is rare. We report a case of pectoralis major pyomyositis caused by Morganella morganii in an 82-year-old Japanese man with type 2 diabetes mellitus who had undergone stenting for myocardial infarction. Four months prior to visiting our hospital, the patient became aware of pain in the right chest area, which gradually became swollen. One month before the visit, the pain and swelling had become more severe. At the visit, there was swelling in the right anterior thoracic region with a diameter of 10 cm and pain in the same region. On physical examination, his blood pressure was 133/64 mmHg, heart rate was 83 beats/min, and body temperature was 36.9℃. Initially, a sarcoma or other neoplastic lesion was suspected and a needle biopsy was performed. Pus was drained from the puncture site to collect wound culture. Needle biopsy of the lesion did not reveal any fungi or acid-fast bacteria, and a T-SPOT.TB test was negative. Computed tomography and magnetic resonance imaging suggested abscess formation under the pectoralis major muscle. A wound culture test detected Morganella morganii, and pectoralis major pyomyositis was diagnosed. Debridement was performed under general anesthesia. The necrotic pectoralis major muscle was excised, the abscess cavity was opened, and wound irrigation was performed. The postoperative course was good and the patient was discharged on the 16th postoperative day. There has been no recurrence in eight months postoperatively. Pectoralis major pyomyositis may not be relieved by antibiotics alone and may extend to deeper organs to form intrapleural abscesses. Therefore, prompt drainage should be performed to prevent serious complications in a case in which abscess formation is observed.

Candida Costochondritis Induced by Traumatic Small Bowel Perforation: A Case Report.

Candida osteomyelitis is a manifestation of invasive candidiasis. The common sites of infection are the vertebra, sternum, and femur, whereas infection of the rib cartilage is very rare. In the present case, candida costochondritis developed after traumatic small-bowel perforation. An 82-year-old man was involved in a traffic accident while walking. His past medical history was insignificant. He was diagnosed with a pelvic fracture and perforation of the small intestine and underwent open reduction and internal fixation of the pelvic fracture and an enterectomy. Three months after the injury, swelling was observed in the right anterior thoracic region. Swelling was treated by incision and drainage but persisted in the form of infected granulation tissue. Debridement, including rib cartilage removal, was done. Biopsy and culture of the removed granulation tissue and cartilage tissue confirmed candida costochondritis. Fluconazole was administered for six months. No recurrence has been observed in the seven months postoperatively. Candida costochondritis is rare but is often refractory and requires extensive debridement in addition to the administration of antifungal agents. This disease should be included in the differential diagnosis when pain, erythema, swelling, skin ulceration, or infected granulation is found on affected costal cartilages.

Staphylococcal Toxic Shock Syndrome after Autologous Breast Reconstruction: A Case Report and Literature Review.

Staphylococcal toxic shock syndrome (TSS) is a rare but potentially life-threatening systemic bacterial intoxication. TSS is characterized by fever, hypotension, rash, digestive symptoms such as vomiting and diarrhea, multiorgan system involvement, and desquamation in the initial recovery period. We report a case of a 35-year-old woman who developed TSS caused by methicillin-resistant Staphylococcus aureus following deep inferior epigastric perforator flap breast reconstruction. Local findings are often not obvious in a case of TSS, which can make early diagnosis and appropriate initial treatment difficult. If a patient presents with characteristic symptoms of TSS after autologous breast reconstruction, TSS should be suspected and exploration of surgical wounds should be initiated as soon as possible.

Impact of skeletal muscle mass on complications following expander breast reconstruction.

Sarcopenia is characterized by skeletal muscle mass (SMM) depletion and decreased muscle power. In two-stage breast reconstruction using a tissue expander, obesity is the main risk factor for postoperative complications. Obese patients with breast cancer and sarcopenia have a hidden lower SMM with a larger body mass index (BMI). This study aimed to investigate the impact of decreased SMM on complications after tissue expander surgery. In this nonrandomized, retrospective cohort study, 157 patients underwent 169 expander indwelling surgeries. Cross-sectional areas (cm2) of skeletal muscles at the third lumbar vertebra were measured on computed tomography (CT) and normalized for height (cm2/m2) to determine the skeletal muscle index (SMI). Subcutaneous and visceral adipose tissue areas were measured in the same slice and normalized for height (cm2/m2) to determine the total adipose tissue index (TATI). The SMI/TATI ratio was calculated as an index of sarcopenic obesity. Postoperative complications occurred in 40 cases (23.7%). In multivariate analysis, a lower SMI/TATI ratio was identified as a significant independent risk factor for complications (P < 0.001, adjusted odds ratio (OR) = 2.28 per 10% decrease). Delayed wound healing was significantly associated with lower SMI/TATI ratio (P = 0.003, OR = 6.33 per 10% decrease) and diabetes (P = 0.044, OR = 7.36). Seroma was significantly associated with high BMI (P < 0.001, OR = 8.00 per 5-kg/m2 increase) and blood loss (P = 0.003, OR = 1.18 per 10 g increase). These results show that patients with a large adipose tissue volume and lower SMM (sarcopenic obesity) have more complications after expander surgery than those with high BMI, or TATI alone.

Impact of skeletal muscle mass on postoperative delirium in patients undergoing free flap repair after oral cancer resection.

Postoperative delirium (POD) is a major risk factor for an extended hospital stay and higher costs, and is associated with increased mortality. The incidence of POD is high in free flap procedures, and POD may also be a risk factor for flap loss and complications. Sarcopenia is a condition characterized by skeletal muscle mass (SMM) depletion and a decrease in muscle power or physical activity. The aim of this study was to investigate risk factors for postoperative delirium (POD), including SMM, in 122 patients undergoing free flap repair after oral cancer resection. All patients underwent preoperative abdominal-lumbar CT or PET-CT. Cross-sectional areas (cm2) of skeletal muscles at the third lumbar vertebra were measured on preoperative CT, normalized for height, and defined as the skeletal muscle index (SMI, cm2/m2). Risk factors for POD were investigated, including the value of SMI and taking the type of POD into consideration. POD occurred in 45 patients (36.9%), and was hyperactive in 28 (62.2%), mixed in 13 (28.9%), and hypoactive in 4 (8.9%). In multivariate analysis, high preoperative albumin (p = 0.046, adjusted odds ratio [OR] = 3.69) and postoperative insomnia (p < 0.001, OR = 6.79) were significant risk factors for POD. In a sub-analysis evaluating risk factors restricted to POD including the hypoactive type, lower SMI (p = 0.035, OR = 2.52 per 10-unit decrease) and postoperative insomnia (p = 0.003, OR = 6.37) were significant. We conclude that lower SMM increases the hypoactive and mixed types of POD. Increasing SMM by exercise and nutritional therapy preoperatively may prevent such POD in free flap repair for oral cancer.

Changes in Skin Perfusion Pressure After Hyperbaric Oxygen Therapy Following Revascularization in Patients With Critical Limb Ischemia: A Preliminary Study.

Hyperbaric oxygen (HBO) therapy promotes wound healing in patients with ischemic disease; however, HBO-induced changes in skin peripheral circulation have not been evaluated in clinical practice. Here, we investigated these changes in patients with critical limb ischemia (CLI), with a focus on the angiosome of crural blood vessels with blood flow improved by endovascular therapy (EVT). Six patients with CLI and ulcers who were treated with HBO after EVT (7 limbs; 1 patient had ulcers in the bilateral limbs) and 3 healthy subjects (6 limbs) were enrolled. HBO therapy was performed at 2 atm under 100% oxygen for 90 min per session. Skin perfusion pressure (SPP) was measured in the dorsum and sole of the foot 1 hour before (pre-SPP) and after (post-SPP) HBO therapy. ΔSPP was calculated as post-SPP minus pre-SPP. SPP measurement regions were divided into those that did (direct region) and did not (indirect region) correspond to the vascular angiosome in which angiography findings of the crus were improved after EVT; i.e., when the anterior tibial artery was effectively treated with EVT, the dorsum was the direct region and the sole was the indirect region, and vice versa when the posterior tibial artery was treated. In the direct, indirect, and healthy subject groups, the ΔSPPs were 20.5±8.7 (p=0.002), -6.4±10.9, and -15.1±18.1 (p=0.014), respectively; that of the direct group was significantly greater than that of the other groups. These results suggest that short-term improvement of the peripheral circulation by HBO therapy was significant in patients with successful revascularization.

Sacral and Rectal Necrosis after Carbon Ion Radiotherapy Reconstructed with Transpelvic Rectus Abdominis Flap.

Carbon ion radiotherapy (CIRT) has been used for malignant tumors that are difficult to excise surgically, such as sacral chordoma, and the success of its outcomes is attributable to the high dose concentration and biological effects. CIRT has produced successful clinical outcomes, and it is considered to have fewer adverse effects on surrounding normal tissues; moreover, complications have been rarely reported. We describe a 75-year-old woman with a full-thickness sacral defect, who had received CIRT for sacral chordoma 3 years earlier. Computed tomography showed sacral bone destruction, and a colonoscopy revealed rectal necrosis. Rectectomy in addition to sacral bone resection was necessary, which resulted in a huge sacral defect of slightly anxious viability. We performed reconstruction of the sacral defect by using pedicled vertical rectus abdominis myocutaneous (VRAM) flap, obliterating sacral defects and intrapelvic dead space that occurred after rectectomy. Six months after surgery, the wound had healed well, and no complication was observed. Sacral complications after CIRT may affect surrounding normal tissues such as the rectum, and it would be difficult to reconstruct the resulting complications. The vertical rectus abdominis myocutaneous flap is considered useful for the simultaneous obliteration of sacral defects and intrapelvic dead space after CIRT.

Quantitative assessment and risk factors for chest wall deformity resulting from tissue expansion for breast reconstruction.

BACKGROUND: Chest wall deformity after tissue expansion for breast reconstruction is less recognized than complications such as infection, hematoma, skin necrosis and capsular contracture. However, the condition should not be discounted because pain, rib fracture and dyspnea may occur in severe cases. The aim of this study is to evaluate the extent of chest wall deformity quantitatively using computed tomography (CT) and to identify risk factors for this condition after tissue expansion. METHODS: The subjects were 34 patients who underwent unilateral two-stage reconstruction and were examined by multidetector-row CT before expander surgery and during maximal tissue expansion. Chest wall deformity was assessed quantitatively using the Chest Wall Deformity Index (CWDI), which was measured before expander surgery (pre-CWDI) and during maximal tissue expansion (post-CWDI). Post minus pre (post-pre) CWDI was used as the index of chest wall deformity in the assessment of risk factors. RESULT: Post-CWDI was significantly higher than pre-CWDI (3.66 ± 3.23% vs. 0.03 ± 2.74%, P < 0.001 by paired t test), showing that chest wall deformity occurred after maximum expansion. In a multiple linear regression model, capsular contracture emerged as a significant predictor of increased post-pre CWDI (P = 0.003). BMI was a significant predictor of decreased post-pre CWDI (P = 0.003), but this result may have been due to the measurement method. CONCLUSIONS: Our findings suggest that chest wall deformity is common after maximum tissue expansion for breast reconstruction. Awareness of the possibility of chest wall deformity during tissue expansion is important, particularly in cases with capsular contracture.

Quantitative assessment and risk factors for nipple-areolar complex malposition after nipple-sparing mastectomy.

PURPOSE: Nipple sparing mastectomy (NSM) for breast cancer preserves the nipple-areola complex (NAC) and has limited the extent of the scar, giving good cosmetic results. However, NAC malposition may occur. The aim of this study is to evaluate NAC malposition after NSM and to determine factors associated with malposition in two-stage reconstruction. METHODS: The subjects were 46 patients who underwent unilateral NSM, without contralateral mastopexy or reduction surgery, in two-stage reconstruction using an expander with implant or flap replacement. Vertical and horizontal NAC malposition and predictors of malposition were evaluated before and more than 1 year after reconstruction surgery. RESULTS: The total amount of saline injected into the expander and aging were significant predictors of increased superior malposition of NAC before and more than 1 year after reconstruction or implant surgery. In contrast, the amount of saline injected into the expander until 2 weeks after expander insertion was a significant predictor of decreased superior NAC malposition. BMI was also a statistically significant predictor of decreased superior NAC malposition, but this result was likely to have been due to the measurement method. Autologous reconstruction was a significant negative predictor of superior malposition at more than 1 year after surgery. Superior NAC malposition resulting from full expansion of the expander improved by a mean vertical angle of 4.5° after autologous reconstruction, but hardly improved after implant use. In autologous reconstruction, NAC tended to move slightly to the lateral side after autologous reconstruction, compared to implant use. CONCLUSIONS: Until 2 weeks after expander insertion, as much saline as possible should be injected to prevent superior NAC malposition. At full expansion, superior malposition of vertical angle > 4.5° may require repositioning surgery.

Open Laparoscopic-assisted Repair of Abdominal Wall Hernia and Bulge.

Rectus abdominalis musculocutaneous (RAM) flaps have numerous uses in the treatment of large defects. However, flap harvesting can result in abdominal wall incisional hernia and bulge, which are challenging problems. Most of these problems occur below the arcuate line abdominal wall. However, there will be differences that are unique to each patient in the area of hernia or bulge. The open approach repair appears to be used most often, but the precise area of hernia and bulge is often not distinguished. This report describes a case that was treated using a new repair method, which had the clear advantage of allowing the precise area of abdominal wall weakness to be recognized. A 53-year-old man underwent left vertical RAM flap for reconstruction after tongue carcinoma resection. Six months after the operation, lower abdominal wall hernia and bulge were observed. Open laparoscopic-assisted repair was performed. Pneumoperitoneum led to distension of the abdominal cavity and outward stretching of the abdominal wall, so that the area of hernia and bulge protruded to a great degree. In this phase, by making the operating room slightly dark, the area became more clearly recognizable. When direct plication of the hernia and bulging area was required, the contralateral component separation technique was performed. This study describes an inventive repair procedure for abdominal wall hernia or bulge after RAM flap, with the combined advantages of open and laparoscopic repair.

The significance of tumor cells-derived MFG-E8 in tumor growth of angiosarcoma.

BACKGROUND: Previous studies have indicated that MFG-E8 enhances tumor cell survival, invasion and angiogenesis. However, the role of MFG-E8 in angiosarcoma (AS) has not been clarified. OBJECTIVE: Objective was to elucidate the mechanism of the regulation by MFG-E8 in AS and the association between MFG-E8 and clinicopathological features of AS. METHODS: The effects of the depletion of MFG-E8 by siRNA on tube formation, migration and proliferation in murine AS cells were examined. The effect of administration of anti-MFG-E8 antibody (Ab) on tumor growth of AS in mice was examined. The associations of MFG-E8 expression and clinicopathological features of human AS were assessed. RESULTS: The expressions of MFG-E8 in murine and human AS cells were significantly higher than those in melanoma cells, macrophages and endothelial cells. Depletion of MFG-E8 in murine AS cells by siRNA significantly inhibited the formation of capillary-like structures and migration, but not proliferation. Administration of anti-MFG-E8 Ab significantly inhibited tumor growth and decreased the number of tumor-associated macrophages (TAMs) in AS tumors. Tumor size and the number of TAMs in human AS with high expression of MFG-E8 were significantly increased compared to those of AS with low expression of MFG-E8. Progression-free survival and overall survival time of the patients of AS with high expression of MFG-E8 were significantly shorter than those of AS with low expression of MFG-E8. CONCLUSIONS: AS-derived MFG-E8 might enhance tumor growth via angiogenesis and the induction of TAMs in autocrine/paracrine manner, and administration of anti-MFG-E8 Ab could be a therapeutic potential for AS.

Zinc deficiency exacerbates pressure ulcers by increasing oxidative stress and ATP in the skin.

BACKGROUND: Zinc deficiency is believed to be a predisposing factor for the development and intractable healing of pressure ulcers (PUs); however, the mechanisms of this association have not been elucidated. OBJECTIVE: Objective was to elucidate the mechanisms of the formation of severe and prolonged PUs under the zinc deficiency condition. METHODS: We assessed PUs formation after cutaneous ischemia-reperfusion (I/R) injury in mice fed with a zinc-adequate (ZA) or a zinc-deficient (ZD) diet from 2 weeks before I/R injury. Wound size, vascular damage, apoptotic cells, adenosine triphosphate (ATP) amount, and the number of Langerhans cells (LCs) in I/R area were analyzed. We evaluated the extent of oxidative stress in I/R area in OKD48 mice through bioluminescence detection. RESULTS: We found that dietary zinc deficiency caused the formation of severe and prolonged PUs in mice. Zinc deficiency increased the vascular disorder, oxidative stress, and apoptosis induced by cutaneous I/R injury. I/R injury-induced oxidative stress signals were significantly higher in ZD OKD48 mice than in ZA OKD48 mice. Additionally, zinc deficiency reduced the number of LCs and increased the amount of ATP in cutaneous I/R-injured skin. Oral supplementation of zinc improved zinc deficiency-associated PUs. CONCLUSION: Zinc deficiency might increase cutaneous I/R injury-induced vascular damages, oxidative stress, and apoptosis, as well as ATP amount in I/R area due to the loss of LCs. These mechanisms might partly account for zinc deficiency-induced formation of severe and prolonged PUs. Oral supplementation of zinc might be a reasonable therapeutic choice for patients with PUs and zinc deficiency.

Botulinum toxin B suppresses the pressure ulcer formation in cutaneous ischemia-reperfusion injury mouse model: Possible regulation of oxidative and endoplasmic reticulum stress.

BACKGROUND: We previously identified that botulinum toxin A (BTX-A) suppressed pressure ulcer (PU) formation after cutaneous ischemia-reperfusion (I/R) injury; however, regulation of cutaneous I/R-induced oxidative and endoplasmic reticulum (ER) stress by BTX-B was not investigated. Additionally, the efficacy of BTX-B injection has never been examined. OBJECTIVE: Objective was to assess the effects of BTX-B on the formation of PU by cutaneous I/R injury, and the regulation of oxidative and ER stress in I/R injury by BTX-B. METHODS: BTX-B was subcutaneously injected into I/R area, and wound size, vascular damage, hypoxic area, and apoptotic cells in I/R area were analyzed. We evaluated the extent of oxidative and ER stress in I/R area by using OKD48 mice and ERAI mice, respectively, which enabled evaluating oxidative and ER stress through bioluminescence detection. RESULTS: BTX-B injection significantly suppressed the formation of PU by cutaneous I/R injury. Cutaneous I/R-induced vascular damage, hypoxic area, and number of oxidative-damaged cells and apoptotic cells were suppressed by BTX-B injection. BTX-B administration significantly inhibited I/R-induced oxidative stress signal in OKD48 mice. BTX-B reduced the I/R-induced oxidative stress-associated factors. BTX-B significantly inhibited the oxidant-induced reactive oxygen species and apoptosis of endothelial cells and fibroblasts. BTX-B significantly inhibited I/R-induced ER stress signal in ERAI mice. Cutaneous I/R injury-induced ER stress-response factors and GRP78/BiP and CHOP-positive cells in I/R area were significantly decreased by BTX-B injection. CONCLUSION: BTX-B injection might have protective effects against PU formation after cutaneous I/R injury by reducing vascular damage, hypoxia-induced oxidative and ER stress, and apoptosis.

Protective effect of mesenchymal stem cells on the pressure ulcer formation by the regulation of oxidative and endoplasmic reticulum stress.

Cutaneous ischemia-reperfusion (I/R) injury is associated with the early pathogenesis of cutaneous pressure ulcers (PUs). The objective of this study was to investigate the effect of mesenchymal stem cells (MSCs) injection on the formation of PUs after I/R injury and determine the underlying mechanisms. We found that the subcutaneous injection of MSCs into areas of I/R injured skin significantly suppressed the formation of PUs. I/R-induced vascular damage, hypoxia, oxidative DNA damage, and apoptosis were decreased by MSCs injection. Oxidative stress signals detected after I/R in OKD48 (Keap1-dependent oxidative stress detector, No-48-luciferase) mice were decreased by the injection of MSCs. In cultured fibroblasts, MSCs-conditioned medium significantly inhibited oxidant-induced reactive oxygen species (ROS) generation and apoptosis. Furthermore, endoplasmic reticulum (ER) stress signals detected after I/R in ERAI (ER stress-activated indicator) mice were also decreased by the injection of MSCs. These results suggest that the injection of MSCs might protect against the development of PUs after cutaneous I/R injury by reducing vascular damage, oxidative cellular damage, oxidative stress, ER stress, and apoptosis.