iPSC-derived megakaryocytes and platelets accelerate wound healing and angiogenesis.

BACKGROUND: Platelet-rich plasma (PRP), which is prepared by concentrating platelets in autologous blood, shows efficacy in chronic skin wounds via multiple growth factors. However, it exhibits heterogeneity across patients, leading to unstable therapeutic efficacy. Human induced pluripotent stem cell (iPSC)-derived megakaryocytes and platelets (iMPs) are capable of providing a stable supply, holding promise as materials for novel platelet concentrate-based therapies. In this context, we evaluated the effect of iMPs on wound healing and validated lyophilization for clinical applications. METHODS: The growth factors released by activated iMPs were measured. The effect of the administration of iMPs on human fibroblasts and human umbilical vein endothelial cells (HUVECs) was investigated in vitro. iMPs were applied to dorsal skin defects of diabetic mice to assess the wound closure rate and quantify collagen deposition and angiogenesis. Following the storage of freeze-dried iMPs (FD-iMPs) for three months, the stability of growth factors and their efficacy in animal models were determined. RESULT: Multiple growth factors that promote wound healing were detected in activated iMPs. iMPs specifically released FGF2 and exhibited a superior enhancement of HUVEC proliferation compared to PRP. Moreover, an RNA-seq analysis revealed that iMPs induce polarization to stalk cells and enhance ANGPTL4 gene expression in HUVECs. Animal studies demonstrated that iMPs promoted wound closure and angiogenesis in chronic wounds caused by diabetes. We also confirmed the long-term stability of growth factors in FD-iMPs and their comparable effects to those of original iMPs in the animal model. CONCLUSION: Our study demonstrates that iMPs promote angiogenesis and wound healing through the activation of vascular endothelial cells. iMPs exhibited more effectiveness than PRP, an effect attributed to the exclusive presence of specific factors including FGF2. Lyophilization enabled the long-term maintenance of the composition of the growth factors and efficacy of the iMPs, therefore contributing to stable supply for clinical application. These findings suggest that iMPs provide a novel treatment for chronic wounds.

Open-Y technique for the internal mammary vein in the free abdominal flap of unilateral breast reconstruction.

BACKGROUND: In microvascular breast reconstruction, the internal mammary vein (IMV) has emerged as the most common recipient vein. The open-Y technique can increase the vessel diameter via the bifurcation site. This study aimed to investigate the open-Y technique for IMV. METHODS: The characteristics and details of the operative procedure in patients who had undergone unilateral breast reconstruction with and without the open-Y approach for the free abdominal flap were compared. Differences in IMV anastomosis site (the bifurcation of the main duct or that of the perforator branch) were also compared in patients with the open-Y technique. The open-Y technique was performed on the IMV side. RESULTS: The open-Y and conventional groups included 127 and 62 patients, respectively. The main duct diameter of IMV was significantly smaller (median 2.5 vs. 3.0 mm, P < 0.001), and the rate of right-sided anastomosis (47.2 vs. 82.3%, P < 0.001) was significantly lower in the open-Y group. When comparing the main duct and perforator groups, the branch diameter (1.8 vs. 1.0 mm, P < 0.001) and the diameter after the open-Y technique (5.0 vs. 3.9 mm, P < 0.001) were significantly higher, and the angle of bifurcation (45° vs. 60°, P = 0.007) was significantly lower in the main duct group. CONCLUSIONS: Given a small venous diameter, the open-Y technique is superior, especially for left-sided breast reconstruction. Owing to the lower angle of bifurcation and large diameter, the open-Y technique at the main duct bifurcation of IMV causes less turbulence in the blood flow. TAKE HOME MESSAGE: The open-Y technique is especially effective for left-sided breast reconstruction. Considering the lower angle of bifurcation and large diameter, the open-Y technique at the main duct bifurcation of the internal mammary vein causes less turbulence in the blood flow.

Senescence-associated inflammation and inhibition of adipogenesis in subcutaneous fat in Werner syndrome.

Werner syndrome (WS) is a hereditary premature aging disorder characterized by visceral fat accumulation and subcutaneous lipoatrophy, resulting in severe insulin resistance. However, its underlying mechanism remains unclear. In this study, we show that senescence-associated inflammation and suppressed adipogenesis play a role in subcutaneous adipose tissue reduction and dysfunction in WS. Clinical data from four Japanese patients with WS revealed significant associations between the decrease of areas of subcutaneous fat and increased insulin resistance measured by the glucose clamp. Adipose-derived stem cells from the stromal vascular fraction derived from WS subcutaneous adipose tissues (WSVF) showed early replicative senescence and a significant increase in the expression of senescence-associated secretory phenotype (SASP) markers. Additionally, adipogenesis and insulin signaling were suppressed in WSVF, and the expression of adipogenesis suppressor genes and SASP-related genes was increased. Rapamycin, an inhibitor of the mammalian target of rapamycin (mTOR), alleviated premature cellular senescence, rescued the decrease in insulin signaling, and extended the lifespan of WS model of C. elegans. To the best of our knowledge, this study is the first to reveal the critical role of cellular senescence in subcutaneous lipoatrophy and severe insulin resistance in WS, highlighting the therapeutic potential of rapamycin for this disease.

Ex vivo dual gene therapy using human adipocytes secreting anti-HER2 antibody on HER2-positive xenograft tumor models.

BACKGROUND: Although targeted treatments against human epidermal growth factor receptor 2 (HER2) have improved survival in patients with metastatic HER2-positive breast cancer, long and repeated treatment is time-consuming and costly for patients. To reduce these burdens, we developed ex vivo gene-transduced adipocytes that secrete anti-HER2 antibodies and evaluated their anti-tumor effects. METHODS: Ceiling culture-derived proliferative adipocytes (ccdPA) secreting anti-HER2 antibody against domain IV receptors: TRA-ccdPA, and domain II receptors: PER-ccdPA, were constructed using a plasmid lentivirus. Delivery of secreted antibody and its specific binding to HER2 breast cancer were evaluated in vitro and in vivo. To optimize antibody production from ccdPA, different conditions of ccdPA implantation were examined. Anti-tumor efficacy was evaluated in HER2-positive-cancer-inoculated nude mice. RESULTS: Anti-HER2 antibody against domain II was identified in supernatants from PER-ccdPAs. The optimal method to achieve the highest concentration of antibody in mouse sera was injecting differentiated ccdPA cells into the mammary fat pad. Antibody in supernatants from PER-ccdPAs bound to the surface of HER2-positive breast cancer cells similar to pertuzumab. Antibodies in mouse sera were delivered to HER2-positive breast cancer tumors and tumor necrosis was observed microscopically. One-time administration of combined TRA-ccdPAs and PER-ccdPAs produced antibody continuously in mouse sera, and anti-tumor effects were maintained for the duration of this study in xenograft models. Furthermore, combination therapy significantly suppressed tumor growth compared with a single administration. CONCLUSION: Ex vivo gene-transduced adipocytes might be useful for cell-based gene therapy. This system may be a platform for various antibody therapies.

Do the Histological Differences of Soft Tissue Sarcomas Affect the Rate of Skin Defect Reconstruction?

BACKGROUND: In soft tissue sarcoma (STS) resection, flap reconstruction and/or skin grafting is frequently required. However, it is not clear whether the histological difference affects the rate of reconstruction. The present study aimed to investigate it. METHODS: This study compared in 5 classifications (105 adipocytic tumors, 102 fibroblastic tumors, 39 muscle tumors, 31 peripheral nerve sheath tumors, and 178 tumors of uncertain differentiation). In addition, the reconstruction rates of detailed tumor sites were compared. The median and case number (percentage) were calculated. RESULTS: Tumor size (adipocytic 112 mm vs fibroblastic 79 mm, muscle 72 mm, nerve 90 mm, uncertain 74 mm, P < 0.0001 in all comparisons), histological low-grade rates (adipocytic 43.8% vs uncertain 3.9%, P < 0.0001; fibroblastic 46.1% vs muscle 15.4%, P = 0.003; fibroblastic vs uncertain, P < 0.0001; nerve 19.4% vs uncertain, P = 0.003) and reconstruction rates (adipocytic 5.7% vs fibroblastic 42.2%, muscle 33.3%, nerve 32.3%, uncertain 25.8%, P < 0.0001 in all comparisons) were significantly different. In the region of lower extremity, the regions of thigh [adipocytic 1/62 (1.6%) vs fibroblastic 7/32 (21.9%), P = 0.002], and lower leg [adipocytic 1/16 (6.3%) vs fibroblastic 11/19 (57.9%), P = 0.002] were significantly different. CONCLUSIONS: In adipocytic tumors, the tumor size was significantly large; however, the skin defect reconstruction rate was significantly lower than that of the other STS. Histologically, the reconstruction rate of STS derived from superficial tissue increases, whereas the reconstruction rate derived from deep tissue such as adipocytic tumor decreases.

Differences in Transient Fluid Retention and Lymphedema With Breast Cancer Treatment for Lymphatic Microsurgery.

BACKGROUND: Breast cancer-related lymphedema (BCRL) is a common complication. Repeated taxane-based chemotherapy has been shown to induce endothelial inflammation, leading to fluid retention. Patients with transient fluid retention only have upper limb edema without lymphatic dysfunction. Therefore, indocyanine green lymphography revealed linear findings, and lymphatic microsurgery is not required. This study aimed to investigate the difference between BCRL and fluid retention and present the indication for lymphatic microsurgery for these patients. METHODS: The study population was divided into BCRL and fluid retention groups. Age, body mass index, laterality, surgery type (lymph node, breast, or no surgery), disease stage, regional lymph node irradiation, hormone therapy, chemotherapy type (taxane- or non-taxane-based group), and treatment with trastuzumab were compared. RESULTS: The BCRL and fluid retention groups consisted of 168 and 73 patients, respectively. The BCRL group had significantly higher rates of axillary lymph node dissection (96.4%) and lymph node irradiation (51.8%) than the fluid retention group (53.4% and 24.7%, respectively; P < 0.001 for both). The fluid retention group had a significantly higher rate of taxane-based chemotherapy (100%) than the BCRL group (92.9%; P = 0.02). No significant differences in other characteristics, including treatments with hormone and trastuzumab, were observed. CONCLUSIONS: Lymphatic microsurgery should be performed after confirming the diagnosis by indocyanine green lymphography, particularly for patients with fluid retention induced by taxane-based chemotherapy. Because the generalized swelling induced by taxane-based chemotherapy is resolved 6 months after chemotherapy, we should wait at least 6 months to perform lymphatic microsurgery.

Fascia turnover procedure at breast reconstruction using free TRAM flap for decreasing umbilical migration.

BACKGROUND: The ideal umbilical position is midway between the two iliac crests. Some patients complained that the umbilicus position shifted from the midline after the breast reconstruction with a free muscle-sparing transverse rectus abdominis musculocutaneous (MS-TRAM) flap. We considered that the fascia of the external oblique muscle could be applied to the rectus abdominis fascia defect. This study aimed to introduce this "fascia turnover procedure" and compare the umbilical position in this procedure with that in primary fascial closure for the MS-TRAM flap of breast reconstruction. METHODS: A total of 152 patients were enrolled (80 patients with fascia turnover (+) vs. 72 patients (-)). The patients' demographics were compared. Horizontal distances (right side: a; left side: b) were measured bilaterally from the lateral abdominal wall to the center of the umbilicus. Frontal abdominal photographs were taken preoperatively (a1, b1) and postoperatively (a2, b2). The rate of umbilical migration (= | (a1 - b1) / (a1 + b1) - (a2 - b2) / (a2 + b2) | × 100%) was calculated. Because the aponeurosis of the external oblique muscle is confirmed in front of the lateral side of the anterior rectus sheath, this procedure could be performed in cases with a medial defect. RESULTS: No significant differences in the patients' demographics, including abdominal bulging rates and abdominal wall defect widths were observed between the two groups. The rate of umbilical migration showed a significant difference (median 1.78% vs. 3.70%, P < 0.001). CONCLUSIONS: This procedure could decrease the rate of umbilical migration.

Correlation between abdominal visceral volume measured by a simple procedure and bulging at the abdominal free flap donor site for breast reconstruction.

BACKGROUND: Breast reconstructions using autologous abdominal tissue result in breasts with a natural shape and consistency. One of the major complications is abdominal bulging. Because of the increased abdominal wall tension, high visceral volume (not visceral fat alone) may increase the occurrence rate of abdominal bulging. A simple procedure involving CT imaging was used to assess this relationship in patients undergoing an abdominal free flap for unilateral breast reconstruction. METHODS: A total of 278 patients were enrolled in this study. The patients' demographics, the thicknesses of visceral volume were compared (Bulging (+) vs. Bulging (-)). Visceral volume was investigated based on the horizontal thickness, which was measured at the thickest part at the level of the umbilical fossa between both sides under the transverse abdominis muscles. RESULTS: Bulging (+) consisted of 39 patients (14.0%), whereas Bulging (-) included 239 patients. Patients with Bulging (+) were significantly older, had higher gestational history rate, and had thin rectus abdominis muscle. In terms of visceral volume, the Bulging (+) group had significantly higher horizontal thicknesses (median 233 mm vs. 219 mm, P < 0.001). No significant differences were observed with respect to other factors (age, BMI, history of laparotomy, and operative details). The multivariate logistic regression analysis revealed that the thickness of the rectus abdominis muscle, horizontal visceral volume, and gestational history were independently significant predictors. CONCLUSIONS: Not only the patients with thin rectus abdominis muscle but also patients with a thick horizontal visceral volume may have a higher risk of abdominal bulging.

Utility of the intraflap perfusion procedure for abdominal free flap in unilateral breast reconstruction.

BACKGROUND: Heparin prophylaxis for venous thromboembolism can be used in microsurgery. If vein anastomosis is performed before the artery, heparin irrigation into the artery can be performed locally without systematic effect. This study aimed to introduce this "intraflap perfusion procedure" in autologous breast reconstruction. METHODS: Among the 220 patients with unilateral breast cancer who had received the free abdominal flap, we retrospectively compared those that had undergone the intraflap perfusion procedure (n = 108) and those who did not (n = 112). A 10 mL injection of heparinized physiological saline solution (100 units/mL) was administered into the deep inferior epigastric artery. Intraflap perfusion was performed before, during, and after vein anastomosis, without the vessel clip of the vein. Artery anastomosis was performed without the use of a vein clamp. Further, vein anastomosis was performed tightly to prevent leakage from the vein anastomosis site during artery anastomosis. RESULTS: The rates of superficial inferior epigastric vein (SIEV) superdrainage (18.5% vs. 42.0%, P < 0.001), and intraoperative flap congestion (0.9% vs. 8.0%, P = 0.01) were significantly lower in patients undergoing this procedure. There were no significant differences regarding other factors (age, BMI, laterality, comorbidities, and other operative details). CONCLUSIONS: Intraflap perfusion prevented long-term stasis at the venous anastomosis site and capillary level. It could reduce flap congestion. SIEV superdrainage was performed to manage flap congestion, particularly in patients who did not undergo this procedure. Consequently, it can be inferred that this procedure reduces the rate of superdrainage.

Scarless Donor Site for Breast Reconstruction by Endoscopy-assisted Extended Latissimus Dorsi Flap plus Lipofilling.

BACKGROUND: Breast reconstruction using endoscopy-assisted latissimus dorsi (LD) flap leaves no scar on the back; however, the small amount of tissue obtained makes this procedure less practical. This study aimed to propose a new technique of endoscopy-assisted extended LD (eeLD) flap plus lipofilling, which could secure a large breast volume. METHODS: Lateral thoracic adipose tissues supplied by the thoracodorsal artery branches and the LD muscle were elevated as a single unit only through the mastectomy scar and three ports through the lateral chest. Further, fat was simultaneously injected to support the volume and shape of the breast. Changes in the volume of the reconstructed breast over time were measured using three-dimensional stereophotogrammetry. RESULTS: Overall, 15 breasts of 14 patients who underwent breast reconstruction using an eeLD flap exhibited no serious complications. On average, 281.9 ± 32.4 g of flap and 74.7 ± 19.4 ml of lipofilling were used. Within 8 weeks after the procedure, the volume of the reconstructed breast decreased to 69.5% ± 7.5% and then plateaued. Seven patients needed a subsequent session of lipofilling to acquire adequate breast volume and projection. Notably, according to the BREAST-Q back scores, patients who underwent eeLD flap were significantly more satisfied than those who underwent conventional LD musculocutaneous flap using a skin paddle on the back at the same institution (82.8 ± 9.2 vs. 62.6 ± 6.3, P < 0.0001). CONCLUSION: Despite the limitations in volume, eeLD flap plus lipofilling is advantageous because it does not leave a noticeable donor site scar.

First-in-human autologous implantation of genetically modified adipocytes expressing LCAT for the treatment of familial LCAT deficiency.

Background: Familial lecithin: cholesterol acyltransferase (LCAT) deficiency (FLD) is a severe inherited disease without effective treatment. Patients with FLD develop severe low HDL, corneal opacity, hemolytic anemia, and renal injury. Objective: We developed genetically modified adipocytes (GMAC) secreting LCAT (LCAT-GMAC) for ex vivo gene therapy. GMACs were prepared from the patient's adipocytes to express LCAT by retroviral gene transduction to secrete functional enzymes. This study aimed to evaluate the safety and efficacy of LCAT-GMAC implantation in an FLD patient. Methods: Proliferative preadipocytes were obtained from a patient using a ceiling culture and retrovirally transduced with LCAT. After obtaining enough cells by expansion culture of the transduced cells, the resulting LCAT-GMACs were implanted into a patient with FLD. To evaluate the safety and efficacy, we analyzed the outcome of the autologous implantation for 24 weeks of observation and subsequent 240 weeks of the follow-up periods. Results: This first-in-human autologous implantation of LCAT-GMACs was shown to be safe by evaluating adverse events. The LCAT-GMAC implantation increased serum LCAT activity by approximately 50% of the baseline and sustained over three years. Consistent with increased LCAT activity, intermediate-density lipoprotein (IDL) and free cholesterol levels of the small and very small HDL fractions decreased. We found the hemoglobin/haptoglobin complex in the hemolyzed pre-implantation sera of the patient. After one week of the implantation, the hemoglobin/haptoglobin complex almost disappeared. Immediately after the implantation, the patient's proteinuria decreased temporarily to mild levels and gradually increased to the baseline. At 48 weeks after implantation, the patient's proteinuria deteriorated with the development of mild hypertension. By the treatment with antihypertensives, the patient's blood pressure normalized. With the normalization of blood pressure, the proteinuria rapidly decreased to mild proteinuria levels. Conclusions: LCAT-GMAC implantation in a patient with FLD is shown to be safe and appears to be effective, in part, for treating anemia and proteinuria in FLD.

Utilization of a partial rib-sparing procedure in microvascular breast reconstruction for preserving intercostal nerve and nipple reconstruction.

BACKGROUND: In microvascular breast reconstruction, internal mammary vessel (IMV) exposure has been performed. The preservation of intercostal nerve (ICN) is effective for preserving sensibility and decreasing postoperative pain. In nipple reconstruction, cartilage grafting is performed to provide additional support and projection. We considered that ICN preservation and costal cartilage banking could be performed simultaneously. This method was described as the "partial rib-sparing procedure." The purpose of this study was to introduce this procedure. METHODS: Surgical technique of this procedure was as follows. The second intercostal space was used. The width of the trimmed cartilage was kept within the superior half of the third costal cartilage. Soft tissue within 5 mm of the inferior border of the second rib edge was preserved to save the second ICN. The length of IMVs in the partial rib-sparing procedure and that in the total rib-sparing procedure was compared. RESULTS: The number of patients in the partial rib-sparing and total rib-sparing groups was 137 procedures and 57 procedures, respectively. The length of IMVs was significantly longer in the partial rib-sparing procedure (median 20.5 mm vs. 17.6 mm, P < 0.001). In the partial rib-sparing group, no patient complained of prolonged local pain, and chest wall contour abnormalities were absent in all cases. CONCLUSIONS: The partial rib-sparing procedure is superior, especially for patients with narrow intercostal spaces and/or patients who decide to undergo nipple reconstruction with costal cartilage. This procedure could be performed to preserve the soft tissues around the ICN and decrease the postoperative pain.

The correlation of flap blood glucose with fat necrosis of free abdominal flap for unilateral breast reconstruction.

BACKGROUND: Flap blood glucose (FBG) measurement is proposed as a monitoring technique. A cause of long-lasting fever could be derived from fat necrosis. If the findings of low FBG correlated with fat necrosis, it could predict the poor cosmetic result and a source of fever. However, this correlation remained unsolved. The purpose of this study was to clarify this correlation in breast reconstruction. METHODS: In the 180 unilateral breast cancer patients (mean age = 49.8 years) performed free abdominal flap, we retrospectively compared the group where fat necrosis occurred with the group where it did not occur (45 patients with fat necrosis vs. 135 patients without). We compared the average of FBG in each postoperative day. RESULTS: The average FBG was significantly lower in patients with fat necrosis in the second postoperative day (115.3 ± 27.3 vs. 126.3 ± 13.7 mg/dl, p = .026) and the third postoperative day (111.1 ± 22.1 vs. 118.8 ± 13.8 mg/dl, p = .036). Mean BMI and inserted total flap weight were significantly higher in patients with the fat necrosis group (24.8 vs. 22.9 kg/m2 , p = .005) (617 vs. 478 g, p = .006). The multivariate analysis revealed early FBG (OR = 0.96, p = .0002) and laterality (right side) (OR = 0.46, p = .043) were independently significant predictors. There were no significant between-group differences regarding other factors (age, systemic blood glucose, comorbidities and operative details). CONCLUSIONS: The possibility of fat necrosis was high for patients with low FBG in the early postoperative day.

Clinical and Histological Effects of Partial Blood Flow Impairment in Vascularized Lymph Node Transfer.

Regarding vascularized lymph node transfer (VLNT) for lymphedema, partial blood flow impairment in transferred lymph node (LN) flaps may adversely affect the therapeutic results. We investigated the clinical and histological effects of partial blood flow impairment in LN flaps. In upper extremity lymphedema cases, based on ultrasonographic examination at 2 weeks after VLNT, we compared the treatment results depending on whether the postoperative blood flow in transferred LNs was good (Group G) or poor (Group P). Novel partial ischemia and congestion of LN flap mouse models were developed to determine their histological features. In 42 cases, significant differences were observed between Group G (n = 37) and Group P (n = 5) based on the amount of volume reduction (136.7 ± 91.7 mL and 55.4 ± 60.4 mL, respectively; p = 0.04) and lymph flow recanalization rate in indocyanine green fluorescent lymphography (67.6% and 0%, respectively; p = 0.0007). In mouse models, thrombi formation in the marginal sinus and numerous Myl9/12-positive immunocompetent cells in follicles were observed in congested LNs. Blood flow maintenance in the transferred LNs is an essential factor influencing the therapeutic effect of VLNT. Postoperatively, surgeons should closely monitor blood flow in the transferred LNs, particularly in cases of congestion.

LCAT-trial-24 weeks: Protocol for a clinical study to evaluate the safety of regenerative medicine and gene therapy by the autologous transplantation of human lecithin:cholesterol acyltransferase gene-transduced human pre-adipocytes.

Backgrounds: Despite the absolute need for life-long treatment of inherited and genetic diseases, there has been little effort to develop such treatments for most of these conditions due to their rarity. Familial lecithin:cholesterol acyltransferase (LCAT) deficiency is recognized as one such orphan disease. We have been developing an adipocyte-based ex vivo gene therapy/regenerative medicine, a novel methodology that differs from the adeno-associated virus-mediated in vivo gene therapy or ex vivo gene-transduced hematopoietic cell therapy, to treat familial LCAT deficiency. Recently, a first-in-human (FIH) clinical study was conducted under the Act on Securement of Safety of Regenerative Medicine, wherein a patient with familial LCAT deficiency was treated. To obtain approval to put this treatment into practical use, a clinical trial has been designed with reference to the FIH clinical study. Methods: An interventional, open-label, unblinded dose-escalation trial was planned, referring to previous FIH clinical study. The trial aims to evaluate the safety of the investigational product in relation to the characteristics of the investigational product (ex vivo gene/cell therapy product by retroviral vector-mediated LCAT gene transduction) using two doses, and the efficacy of the treatment will be evaluated exploratively. A total of three patients will be enrolled sequentially and followed for 24 weeks after administration. This study is designed as a multicenter trial, with Chiba University Hospital administering and evaluating the safety/efficacy of the investigational products at the prescribed visit. Conclusion: This clinical trial is expected to facilitate the provision of lifelong treatment to many patients with LCAT deficiency. Trial registration number: Japan Registry of Clinical Trials (jRCT2033200096).

Relationship between Preoperative Abdominal Wall Strength and Bulging at the Abdominal Free Flap Donor Site for Breast Reconstruction.

BACKGROUND: Abdominal bulging at the donor site of free abdominal flaps for breast reconstruction is a common postoperative complication. In addition to the thickness of abdominal muscles, the authors identified the rectus abdominis diastasis as an important factor that compromises abdominal wall strength. This study aimed to assess the relationship between preoperative abdominal wall strength and postoperative abdominal bulging. METHODS: A total of 224 patients were enrolled in this study. Patient demographics, the rectus and lateral abdominis muscle thicknesses, and the rate of rectus abdominis diastasis were compared (with versus without bulging). Muscle thickness and rectus abdominis diastasis were investigated by preoperative computed tomography. RESULTS: The group with bulging consisted of 32 patients (14.3 percent), whereas the group without bulging consisted of 192 patients. The group with bulging had a significantly higher gestational history rate. The thickness of the rectus abdominis muscle in the group with bulging was significantly thinner (median, 8.6 mm versus 10.5 mm; p < 0.001) and the rate of rectus abdominis diastasis was significantly higher (78.1 percent versus 32.3 percent; p < 0.001). There were no significant differences with respect to the thickness of the lateral abdominal muscle and the other factors (i.e., age, body mass index, history of laparotomy. and operative details). CONCLUSIONS: Because the diagnosis of abdominal bulging was based on severity, the rate may be high compared to that reported from previous studies. Because the factor of gestational history correlated to thickness of the rectus abdominis muscle and rectus abdominis diastasis, this factor influenced the occurrence of abdominal bulging. Patients with a thin rectus abdominis muscle and rectus abdominis diastasis were at higher risk of abdominal bulging. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.