Repeated Fluid Accumulation around a Breast Implant Related to Synovial Metaplasia of the Capsule.

We must take special care when treating postoperative fluid accumulation around breast implants (BIs) to exclude any serious complications, including BI-associated anaplastic large cell lymphoma. However, most late-onset fluid accumulation is caused by other conditions, such as traumatic hematoma and residual postoperative seroma. Surgeons must choose whether to conservatively observe or remove such BIs, while also determining whether to perform partial capsulectomy or total capsulectomy to solve the problem of fluid accumulation. We treated a 72-year-old woman who noticed swelling in her right breast 4 years after undergoing bilateral BI reconstruction. Before she was referred to our hospital, the fluid had been drained by needle aspiration five times, but the swelling returned to a similar size within a month. No malignant findings were observed by needle-aspirated cytology or flow cytometry. The patient requested the simultaneous removal of the left BI. Therefore, we performed both BI removal with total capsulectomy on the right side and partial capsulectomy of the superficial layer on the left side. A pathological examination of the capsule on the right side indicated a chronic expanding hematoma and synovial metaplasia characterized by papillary projections rich in CD68-positive cells, thus indicating reactive synovial cells. In contrast, the left superficial capsule was much thinner and showed less synovial metaplasia. Our findings indicate the advantages of total capsulectomy to solve the problem of repeated serous fluid accumulation around BIs, according to histological changes in the capsule.

Efficacy of foam sclerotherapy with polidocanol for the management of oral venous malformations.

The present aimed to examine the effectiveness of polidocanol-based foam sclerotherapy for oral venous malformations (OVMs). The present study performed a retrospective analysis of patients with OVMs who underwent sclerotherapy using polidocanol. Patients achieving the complete resolution of OVM were categorized as having a complete response (CR), those with a reduction in size from the initial diagnosis were categorized as having a partial response (PR), those with no change in size as stable disease (SD), and those with an increase in size as progressive disease (PD). A total of 16 patients, comprising 4 males and 12 females, underwent treatment with polidocanol foam therapy, covering 22 affected areas. The treatment administered resulted in CR in 6 cases and PR in 10 cases, with no instances of SD or PD. Apart from localized injection site pain or swelling, there were no severe side-effects reported, such as circulatory dynamic changes or skin necrosis. On the whole, these findings underscore the effectiveness of foam sclerotherapy with polidocanol as a viable treatment for venous malformations in the oral and maxillofacial regions.

A Phase 2, Prospective, Multicenter, Single-Arm Trial of Transarterial Chemoembolization Therapy in Combination Strategy with Lenvatinib in Patients with Unresectable Intermediate-Stage Hepatocellular Carcinoma: TACTICS-L Trial.

Introduction: Transarterial chemoembolization (TACE) is the standard treatment for unresectable intermediate-stage hepatocellular carcinoma (HCC), but recurrence after TACE is common. The present phase 2, prospective, multicenter, single-arm trial, the TACTICS-L trial, investigated the efficacy and safety of TACE plus lenvatinib (LEN), a drug that more strongly promotes vascular normalization and has a better objective response rate (ORR) than sorafenib (jRCTs031180074). Methods: Participants were patients with HCC who had not previously received systemic therapy, hepatic arterial infusion chemotherapy, or immunotherapy and who were ineligible for resection or percutaneous ablation therapy. LEN was to be administered 14-21 days before the first TACE, stopped 2 days before TACE, and resumed 3 days after TACE. Key inclusion criteria were unresectable HCC, Child-Pugh A liver function, 0-2 prior TACE sessions, tumor size ≤10 cm, number of tumors ≤10, and ECOG performance status 0-1. Key exclusion criteria were vascular invasion and extrahepatic spread. The primary endpoint was progression-free survival (PFS) by RECICL, and secondary endpoints were time to untreatable progression, ORR, overall survival (OS), and safety. Results: A total of 62 HCC patients were enrolled in this trial. The median age was 72 years, 77.4% of patients were men, and 95.2% had PS 0. The primary endpoint of median PFS was 28.0 months (90% confidence interval [CI] 25.1-31.0) after a minimum 24 months of follow-up. The secondary endpoint of median OS was not reached (90% CI 35.5 months-NR). LEN-TACE achieved a high response rate and high complete response (CR) rate (4 weeks after the first TACE: ORR 79.0%, CR rate 53.2%; best response: ORR 88.7%, CR rate 67.7%) by RECICL. Exploratory subgroup analyses showed that the characteristics of responders/nonresponders (ORR and CR rate) were similar and that LEN-TACE would be effective in all subgroups, including the population in whom TACE alone would be less likely to be curative (e.g., patients with the non-simple nodular type or a high tumor burden). The relative dose intensity of LEN before the first TACE was important for achieving higher CR rate/ORR by LEN-TACE. No new safety concerns were observed. Conclusion: The results of this trial provide encouraging evidence, supporting the efficacy and favorable safety profile of LEN-TACE in patients who are ineligible for locoregional therapy.

Evaluation of adipogenesis over time using a novel bioabsorbable implant without the addition of exogenous cells or growth factors.

Background: Breast reconstruction is crucial for patients who have undergone mastectomy for breast cancer. Our bioabsorbable implants comprising an outer poly-l-lactic acid mesh and an inner component filled with collagen sponge promote and retain adipogenesis in vivo without the addition of exogenous cells or growth factors. In this study, we evaluated adipogenesis over time histologically and at the gene expression level using this implant in a rodent model. Methods: The implants were inserted in the inguinal and dorsal regions of the animals. At 1, 3, 6, and 12 months post-operation, the weight, volume, and histological assessment of all newly formed tissue were performed. We analyzed the formation of new adipose tissue using multiphoton microscopy and RNA sequencing. Results: Both in the inguinal and dorsal regions, adipose tissue began to form 1 month post-operation in the peripheral area. Angiogenesis into implants was observed until 3 months. At 6 months, microvessels matured and the amount of newly generated adipose tissue peaked and was uniformly distributed inside implants. The amount of newly generated adipose tissue decreased from 6 to 12 months but at 12 months, adipose tissue was equivalent to the native tissue histologically and in terms of gene expression. Conclusions: Our bioabsorbable implants could induce normal adipogenesis into the implants after subcutaneous implantation. Our implants can serve as a novel and safe material for breast reconstruction without requiring exogenous cells or growth factors.

PreFlap: From Photoacoustic Tomography Images to Vascular Mapping Sheets for Improved Preoperative Flap Evaluation.

OBJECTIVE: Advancements in technology have improved image acquisition and processing in the field of medical imaging, giving medical doctors the tools to implement effective medical care. In plastic surgery, despite advances in anatomical knowledge and technology, problems in preoperative planning for flap surgery remain. METHODS: In this study, we propose a new protocol to analyze three-dimensional (3D) Photoacoustic tomography images and generate two-dimensional (2D) mapping sheets that can help surgeons identify perforators and the perfusion territory during preoperative planning. The core of this protocol is PreFlap, a new algorithm that converts 3D photoacoustic tomography images into 2D vascular mapping images. CONCLUSION: Experimental results demonstrate that PreFlap can improve preoperative flap evaluation, thus can greatly saving surgeons' time and improving surgical outcomes.

A Prospective Study Exploring the Safety and Efficacy of Lenvatinib for Patients with Advanced Hepatocellular Carcinoma and High Tumor Burden: The LAUNCH Study.

PURPOSE: This study aimed to investigate the safety and efficacy of lenvatinib in real-world settings, including patients excluded from the REFLECT trial, a phase III trial that compared lenvatinib with sorafenib. PATIENTS AND METHODS: This multicenter, nonrandomized, open-label prospective study was conducted at 10 medical facilities in Japan (jRCTs031190017). Eligible patients had advanced hepatocellular carcinoma (HCC) and were suitable for lenvatinib therapy. The study included patients with high tumor burden (with >50% intrahepatic tumor volume, main portal vein invasion, or bile duct invasion), Child-Pugh B status, and receiving lenvatinib as second-line therapy following atezolizumab plus bevacizumab. RESULTS: From December 2019 to September 2021, 59 patients were analyzed (47 and 12 patients with Child-Pugh A and B, respectively). In patients with Child-Pugh A, the frequency of aspartate aminotransferase elevation was high (72.7%) in the high-burden group. No other significant ad verse events (AE) were observed even in second-line treatment. However, patients with Child-Pugh B had high incidence of grade ≥3 AE (100.0%) and high discontinuation rates caused by AE (33.3%) compared with patients with Child-Pugh A (80.9% and 17.0%, respectively). Median progression-free survival was 6.4 and 2.5 months and median overall survival was 19.7 and 4.1 months in Child-Pugh A and B, respectively. Lenvatinib plasma concentration was higher in patients with Child-Pugh B on days 8 and 15 and correlated with dose modifications and lower relative dose intensity. CONCLUSIONS: Lenvatinib is safe and effective for advanced HCC in patients with Child-Pugh A, even with high tumor burden. However, it carries a higher risk of AE and may not provide adequate efficacy for patients with Child-Pugh B status.

Incidence of neurocutaneous melanosis in Japanese pediatric patients with congenital melanocytic nevi.

Neurocutaneous melanosis (NCM) is a rare, non-hereditary neurocutaneous disorder characterized by excessive melanocytic proliferation in the skin and central nervous system. As no major studies have covered the incidence of NCM among Japanese patients with congenital melanocytic nevi (CMN), we prospectively investigated the incidence of NCM among Japanese patients who underwent initial treatment for CMN. The relationship of CMN and NCM was also investigated. Japanese pediatric patients with CMN under 1 year of age were included between January 2020 and November 2022, and all patients underwent brain MRI to check for NCM in this study. NCM lesions were most frequently seen in the amygdala, followed by the cerebellum, brainstem, and cerebral hemispheres. NCM was diagnosed on brain MRI in 31.6% of the 38 patients with CMN and in 25.0% of patients with no prior examination or treatment. Distribution and size of CMN, number of satellite nevi, rugosity and nodules were strongly associated with the existence of NCM, and these findings may guide a future registry study with a large cohort of CMN patients.

Flap Viability Evaluation Using a Tissue Oximetry Camera as an Alternative to Indocyanine Green Fluorescence Imaging.

Indocyanine green (ICG) fluorescence imaging is useful for assessing flap viability; however, it is associated with a risk of anaphylactic shock, even in patients with no history of drug allergies. SnapshotNIR is a noncontact, camera-type handheld tissue oximeter that can measure the tissue oxygen saturation of the body surface. The device emits red and near infrared light wavelengths and then optimizes the measurement of the differential reflectance from oxygenated and deoxygenated hemoglobin, and StO2 is calculated. A 20 × 15 cm surgical field can be evaluated in less than 3 seconds by holding the camera at a distance of 30 cm. We applied this device at zone II in a deep inferior epigastric perforator (DIEP) flap, and compared the findings with the border of flap perfusion detected by ICG imaging. Left breast reconstruction using a free DIEP flap was performed for a 60-year-old woman. The DIEP flap was vascularized by a perforator vessel coursing to the right abdominis muscle. First, Diagnogreen (5 mg; Daiichi Sankyo Co., Tokyo, Japan) was intravenously injected, and the ICG fluorescence perfusion border detected by PDE-neo (Hamamatsu Photonics, Hamamatsu City, Shizuoka, Japan) was determined. The ICG border was defined by two reconstructive surgeons after fluorescence had spread out for 2 minutes. Next, zones Ⅱ and Ⅳ of the DIEP flap, contralateral to the perforator, were evaluated using photographs obtained by SnapshotNIR. There were significant StO2 value differences between the ICG-negative area and ICG-positive area. This device can be widely applied in the noninvasive evaluation of flap viability.

Comparisons of the effects of silk elastin and collagen sponges on wound healing in murine models.

Introductions: Silk elastin, a recombinant protein with repeats of elastin and silk fibroin, possesses a self-gelling ability and is a potential wound dressing material. The aim of this study is to elucidate the mechanism of the wound healing-promoting effect of silk elastin by comparing its in vivo behavior in a mouse wound model with that of a collagen sponge. Methods: Skin defects (8 mm in diameter) were created on the backs of C57BL/6J and BKS.Cg- + Lepr/+Lepr db male mice. Silk elastin sponges of 2.5 or 5.0 mm thickness, as well as collagen sponges, were placed on the wounds and secured with a polyurethane film. In the control group, only the polyurethane film was applied. The remaining wound area was grossly evaluated, and tissue samples were collected after 7, 14, and 21 days for histological evaluation, including neoepithelialization, wound contraction, granulation tissue formation, newly formed capillaries, and macrophages. Genetic analysis was conducted using real-time polymerase chain reaction. Results: In the study with C57BL/6J, there were no significant differences between the silk elastin and collagen sponge groups. Similarly, in the study using BKS.Cg- + Lepr/+Lepr db, no significant differences were found in the remaining wound area and granulation tissue formation between the silk elastin and collagen sponge groups. However, on day 14, the 5.0-mm-thick silk elastin sponge group showed increased macrophages, longer neoepithelialization, and more frequent angiogenesis compared to other groups. Gene expression of inducible nitric oxide synthase and arginase-1 was also higher in the 5.0 mm thick silk elastin sponge group. Conclusions: Silk elastin sponges demonstrated superior neoepithelialization and angiogenesis compared to collagen sponges. The results suggest that silk elastin and collagen sponges promote wound healing through different mechanisms, with silk elastin possibly enhancing wound healing by facilitating increased macrophage migration. Further studies are needed, but silk elastin shows great potential as a versatile wound dressing material.

Long term observation of de novo adipogenesis using novel bioabsorbable implants with larger size in a porcine model.

Introduction: The regeneration of adipose tissue in patients after breast cancer surgery would be desirable without the use of growth factors or cells to avoid potential recurrence and metastasis. We reported that prolate spheroidal-shaped poly-L-lactic acid (PLLA) mesh implants of approximately 18-mm polar diameter and 7.5-mm greatest equatorial diameter containing collagen sponge (CS) would be replaced by regenerated adipose tissue after implantation, thereby suggesting an innovative method for breast reconstruction. Our study aimed to evaluate the adipose tissue regeneration ability of implant aggregates in a porcine model. Methods: We prepared implant aggregates consisting of thirty PLLA mesh implants containing CS packed in a woven poly (glycolic acid) bag. The implant aggregates were inserted under the mammary glands in the porcine abdomen for a year. Single and double groups were classified by inserting either one or two implant aggregates on each side of the abdomen, respectively. Results: In both groups, the volume of the implant aggregates decreased over time, and the formation of adipose tissue peaked between 6 and 9 months. Histologically, the formation of adipose tissue was confirmed in the area that was in contact with native adipose tissue. Conclusions: Our implant aggregates could induce the autologous adipose tissue after long term implantation in vivo, without the use of any growth factor or cell treatment, presenting a potential novel method of breast reconstruction.

An easy-to-use semi-automatic volumetric evaluation for secondary bone grafting in patients with unilateral alveolar cleft.

Surgical intervention for alveolar bone formation is important in patients with alveolar cleft; however, the treatment methods and materials are still controversial. A precise evaluation method for postoperative bone formation is important for comparing outcomes and establishing the best treatment protocol. The purpose of this study is to establish a new method of evaluating surgical outcomes for patients with alveolar cleft. Computed tomography datasets from 20 patients who underwent secondary alveolar bone grafting were obtained before and 1 year after surgery. Six anatomical landmarks were used to superimpose the preoperative and mirrored preoperative volume and postoperative volume data. The cleft region was segmented by subtracting the preoperative from mirrored preoperative volume data, and the failed osteogenesis region was segmented by subtracting the postoperative volume data from the cleft region; subsequently, the bone formation ratio was calculated. Two observers performed this method using a free software 3D slicer and the average evaluation times were 12.7 and 13.2 min for observers 1 and 2, respectively. Method reliability was determined by evaluating intraclass correlation coefficients. The intra-observer intraclass correlation coefficients were 0.97 and 0.96 for observers 1 and 2, respectively. The inter-observer intraclass correlation coefficient was 0.97. Our method is practical for assessing bone formation after treatment, which does not require specific knowledge or software and can be used by ordinary physicians.

The volume-outcome relationship in free-flap reconstruction: A nationwide study based on the Clinical Database.

BACKGROUND: The association between successful reconstructive surgery with a free flap and hospital volume has not been well established. This study was designed to retrospectively analyze the outcome of free-flap surgery registered in a nationwide surgical registration system in Japan to clarify the relationship between free-flap survival and facilities' average annual number of free-flap surgeries. METHODS: We analyzed data from 19,482 free flaps performed during 2017-2020 at 407 facilities throughout Japan. After adjusting for sex, age, and disease classification that differ between the groups, we examined the differences in the flap survival rates among the different facilities in terms of the average number of free-flap surgeries performed annually. RESULTS: The total overall necrosis rate was 2.8%. Of all procedures, 14.9%, 12.9%, 33.4%, and 38.8% were performed at facilities with an average number of free-flap procedures <10, 10-19, 20-49, and ≥ 50 per year, respectively, and the respective rates of total necrosis were 6.0%, 3.8%, 2.1%, and 1.7%, respectively. The odds ratios and 95% confidence intervals of flap necrosis for facilities with ≥ 50 cases per year relative to those <10 were 2.70 (1.98-3.68) for nonbreast reconstruction cases and 5.72 (2.77-11.8) for breast reconstruction cases. CONCLUSION: This analysis of a nationwide plastic surgery database showed that free-flap surgeries in institutions with a low average annual number of free-flap surgeries had a higher risk of total necrosis. Measures should be taken to either aggregate cases into high-volume centers or improve management at low-volume centers.

Development of a Self-Assembled Dermal Substitute from Human Fibroblasts Using Long-term Three-Dimensional Culture.

Skin substitutes have emerged as an alternative to autografts for the treatment of skin defects. Among them, scaffold-based dermal substitutes have been extensively studied; however, they have certain limitations, such as delayed vascularization, limited elasticity, and the inability to achieve permanent engraftment. Self-assembled, cell-based dermal substitutes are a promising alternative that may overcome these shortcomings but have not yet been developed. In this study, we successfully developed a cell-based dermal substitute (cultured dermis) through the long-term culture of human dermal fibroblasts using the net-mold method, which enables three-dimensional cell culture without the use of a scaffold. Spheroids prepared from human dermal fibroblasts were poured into a net-shaped mold and cultured for 2, 4, or 6 months. The dry weight, tensile strength, collagen and glycosaminoglycan levels, and cell proliferation capacity were assessed and compared among the 2-, 4-, and 6-month culture periods. We found that collagen and glycosaminoglycan levels decreased over time, while the dry weight remained unchanged. Tensile strength increased at 4 months, suggesting that remodeling had progressed. In addition, the cell proliferation capacity was maintained, even after a 6-month culture period. Unexpectedly, the internal part of the cultured dermis became fragile, resulting in the division of the cultured dermis into two collagen-rich tissues, each of which had a thickness of 400 µm and sufficient strength to be sutured during in vivo analysis. The divided 4-month cultured dermis was transplanted to skin defects of immunocompromised mice and its wound healing effects were compared to those of a clinically available collagen-based artificial dermis. The cultured dermis promoted epithelialization and angiogenesis more effectively than the collagen-based artificial dermis. Although further improvements are needed, such as the shortening of the culture period and increasing the size of the cultured dermis, we believe that the cultured dermis presented in this study has the potential to be an innovative material for permanent skin coverage.

Development of new bioabsorbable implants with de novo adipogenesis.

Poly-L-lactic acid (PLLA) mesh implants containing collagen sponge (CS) were replaced with autologous adipose tissue regeneration in vivo. Herein, we investigated the optimal external frames and internal fillings using poly (lactic-co-ε-caprolactone) (P (LA/CL)), PLLA, and low-molecular-weight PLLA (LMW-PLLA) as the external frame and polyglycolic acid (PGA) nanosheets and CS as the internal filling. We prepared six implants: P (LA/CL) with PGA nano, PLLA with PGA nano, PLLA with CS, PLLA with 1/2 CS, PLLA with 1/4 CS, and LMW-PLLA with CS, and evaluated adipogenesis at 6 and 12 months using a rat inguinal model. The internal spaces in the P (LA/CL) and LMW-PLLA implants collapsed at 6 months, whereas those in the other four implants collapsed at 12 months. Adipose tissue regeneration was not significantly different between the PLLA-implanted groups at 6 and 12 months and was greater than that in the P (LA/CL) with PGA nano and LMW-PLLA with CS groups. The PGA nanosheet inside PLLA was comparable to the CS inside PLLA in the regeneration of adipose tissue and macrophage infiltration. In summary, PLLA is a promising external frame material in which the internal space can be replaced with adipose tissue. Thus, PGA nanosheets are an alternative internal filling material for adipose tissue regeneration.

Interposition grafting of collagen-gelatin sponge impregnated with basic fibroblast growth factor in primary palatoplasty.

Introduction: An oronasal fistula is a challenging post-operative complication of palatoplasty due to impaired velopharyngeal function or its high recurrence rate. Muscle repositioning, a key procedure in palatoplasty, causes dead space at the junction between the hard and soft palates. Consequently, thin oral and nasal mucosae are prone to break down and form fistulas. In this study, we used basic fibroblast growth factor-impregnated collagen gelatin sponge (bFGF-CGS) in primary palatoplasty to reduce fistula formation. Methods: This retrospective study assessed the complications and efficacy of bFGF-CGS to reduce fistula formation. Patients who underwent primary palatoplasty with bFGF-CGS were included. The same number of patients who underwent primary palatoplasty without bFGF-CGS was included as a control group. The outcomes included post-operative oronasal fistula formation, delayed healing, bleeding, and infection. Results: Both groups included 44 patients. Except for age at palatoplasty, there were no statistically significant demographic differences between the two groups; however, the rates of fistula formation in the study and control group were 2.3% and 13.6%, respectively. There were no infections among the patients. Conclusions: The grafting of bFGF-CGS in primary palatoplasty was safe and probably effective in reducing post-operative oronasal fistula formation.

A high-hydrostatic pressure device for nevus tissue inactivation and dermal regeneration for reconstructing skin defects after giant congenital melanocytic nevus excision: a clinical trial.

Background: A novel treatment has been developed to reconstruct large skin defects caused by the excision of giant congenital melanocytic nevi. It involves the reimplantation of high-hydrostatic pressurized nevus tissue as a cell-inactivated autologous scaffold for dermal regeneration, followed by the implantation of cultured epithelial autografts on the regenerated dermis. Because this treatment has shown promise in a first-in-human clinical trial which used a prototype pressure machine, a novel pressure device was specifically designed for clinical use. Methods: In a prospective investigator-initiated clinical trial involving three patients, we evaluated the safety and efficacy of the skin regeneration treatment using a pressure device. All three patients underwent surgical excision of the nevus tissue, primary reimplantation of the inactivated nevus tissue, and secondary implantation of cultured epithelial autografts. Results: Engraftment of inactivated nevus tissue and cultured epithelial autografts was successful in all three cases, with over 90% epithelialization at 8 weeks post-surgery. No serious adverse events or device malfunction were observed during the trial. Conclusion: The novel pressure device safely and effectively enabled dermal regeneration using the nevus tissue as an autologous scaffold. This innovative approach offers several advantages, including reduced invasiveness due to minimal sacrifice of normal skin for skin grafting and high curative potential resulting from full-thickness removal of the nevus tissue.

Pelvic shape change in adult Japanese macaques and implications for childbirth at old age.

Pelvic morphology exhibits a particular sexual dimorphism in humans, which reflects obstetrical constraints due to the tight fit between neonates and mothers. Huseynov et al. [Proc. Natl. Acad. Sci. U.S.A. 113, 5227-5232 (2016)] showed that in humans, pelvic sexual dimorphism is greatest around the age of highest fertility, and it becomes less marked in association with menopause in females. They proposed that this reflects changes of obstetrical versus locomotor functional demands in females. It remains unknown whether such developmental adjustment of the pelvic morphology is unique to humans. Macaques exhibit human-like cephalopelvic proportions, but they lack menopause and usually maintain fertility throughout adulthood. Here, we track pelvic development in Japanese macaques from neonate to advanced ages using computed tomography-based data. We show that female pelvic morphology changes throughout adult life, reaching the obstetrically most favorable shape at advanced ages rather than around primiparity. We hypothesize that pelvic morphology in Japanese macaques is developmentally adjusted to childbirth at advanced ages, where obstetrical risks are potentially higher than at younger ages. Our data contribute to the growing evidence that the female primate pelvis changes its morphology during the whole lifespan, possibly adjusting for changing functional demands during adulthood.