The Vertical Rectus Abdominis Myocutaneous Flap to Manage Vaginal Evisceration.

BACKGROUND: Pelvic organ prolapse (POP) is a significant issue requiring surgical correction in 19% of the female population by age 85 years. Complications of POP, especially in women who have undergone hysterectomy, include vaginal evisceration-a serious complication that carries high morbidity and mortality rates. Rarely, vaginal evisceration occurs after colpocleisis. CASE: A 69-year-old female with recurrent vaginal evisceration following colpocleisis underwent surgical repair using a vertical rectus abdominis myocutaneous (VRAM) flap. CONCLUSION: Recurrent cases of POP and vaginal evisceration that are refractory to conventional treatment require consideration of novel management options. To our knowledge, this is the first case using a VRAM flap for the management of vaginal evisceration.

Biomechanical Principles of Breast Implants and Current State of Research in Soft Tissue Engineering for Cosmetic Breast Augmentation.

Currently there are limited implant-based options for cosmetic breast augmentation, and problems associated with those have been increasingly appreciated, most commonly capsular contracture, which occurs due to a chronic foreign body reaction against non-degradable implant materials such as silicone and polyurethane leading to scar tissue formation, pain, and deformity. The underlying biomechanical concepts with implants create a reciprocal stress-strain relationship with local tissue, whilst acting as a deforming force. This means that with time, as the implant continues to have an effect on surrounding tissue the implant and host's biomechanical properties diverge, making malposition, asymmetry, and other complications more likely. Research directed towards development of alternative therapies based on tissue engineering and regenerative medicine seeks to optimize new tissue formation through modulation of tissue progenitors and facilitating tissue regeneration. Scaffolds can guide the process of new tissue formation by providing both an implant surface and a three-dimensional space that promotes the development of a microenvironment that guides attachment, migration, proliferation, and differentiation of connective tissue progenitors. Important to scaffold design are the architecture, surface chemistry, mechanical properties, and biomaterial used. Scaffolds provide a void in which vascularization, new tissue formation, and remodelling can sequentially occur. They provide a conduit for delivery of the different cell types required for tissue regeneration into a graft site, facilitating their retention and distribution. Whilst recent research from a small number of groups is promising, there are still ongoing challenges to achieving clinical translation. This article summarizes the biomechanical principles of breast implants, how these impact outcomes, and progress in scaffold-guided tissue engineering approaches to cosmetic breast augmentation. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Patients with in-transit melanoma metastases have comparable survival outcomes following isolated limb infusion or intralesional PV-10-A propensity score matched, single center study.

BACKGROUND AND OBJECTIVE: Isolated limb infusion (ILI) and intralesional PV-10 are well described locoregional therapies for in-transit melanoma. The objective of this study was to assess the effect of these treatments on survival outcomes within a cohort matched for key characteristics. METHODS: Patients were treated using ILI or intralesional PV-10 at a single institution and the data prospectively recorded. Propensity score matching was performed using key covariates within a logistic regression model. The primary outcome was the melanoma-specific survival. RESULTS: Seventy-two patients nonrandomized were successfully matched. Both treatments produced similar best overall responses. The median melanoma-specific survival (MSS) was 74.4 months from ILI and 36.4 months from PV-10 treatments (P = 0.164). Within the ILI subgroup, the 12-, 24-, 36- and 60-month MSS rates were 85.3%, 75.3%, 60.1%, and 60.1%, respectively. From the time of PV-10 the corresponding 12-, 24-, 36-, and 60-month MSS rates were 82.6%, 70.0%, 53.9%, and 35.9%. On multivariate analysis, there was a significant difference in survival comparing completely with noncomplete responders ( P = 0.031). CONCLUSIONS: These findings demonstrate that ILI and PV-10 treatments for in-transit disease produce comparable long-term survival. Both therapies have reproducible response rates and predominantly localized and tolerable side-effects.

A systematic review and meta-analysis of locoregional treatments for in-transit melanoma.

BACKGROUND AND OBJECTIVES: In-transit melanoma (ITM) metastases present a therapeutic challenge and management decisions can be difficult. There are multiple treatments available, with differing efficacy, and supported by different levels of evidence. The primary objective was to perform a systematic review and where suitable, a meta-analysis of the literature reporting on the use of locoregional treatments for the management of ITM. METHODS: An independent review was conducted including a comprehensive search of the National Library of Medicine using PubMed, MEDLINE, Embase, and Cochrane Library databases. Key data were tabulated, synthesized and pooled to calculate relevant weighted effect sizes for each therapy using random-effect models. The statistical heterogeneity was calculated using the Higgins' method. RESULTS: Of the initial 32 612 articles identified, 57 original articles satisfied eligibility criteria. Eight treatment modalities were identified comprising: amputation (7); hyperthermic isolated limb perfusion (15); isolated limb infusion (8); carbon dioxide laser (9); PV-10 intralesional therapy (5); IL-2 intralesional therapy (8); imiquimod (7); diphenylcyclopropenone (3). Only amputation and topical imiquimod were suitable for formal meta-analysis. CONCLUSIONS: All of the assessed therapies have significant selection bias. Variable levels of evidence support the ongoing use of locoregional treatments and these may significantly improve disease-free survival.

Intralesional PV-10 for the treatment of in-transit melanoma metastases-Results of a prospective, non-randomized, single center study.

BACKGROUND: Patients with in-transit melanoma metastases frequently experience high rates of recurrence, limited overall survival and reduced quality of life. After promising results within a Phase II, multi-center study, PV-10 treatment was continued at our institution for patients with in-transit disease. METHODOLOGY: An open-label, non-randomized, prospective study was performed at the Princess Alexandra Hospital, Queensland, Australia. Patients were treated with PV-10 in accordance with the treatment protocol established during a previous Phase II study. The primary outcome was the complete response of treated lesions. RESULTS: Forty-five patients were enrolled over a total of 82 treatment episodes from July 2008 to December 2015. With sequential PV-10 treatments the complete response rate was 42% and overall response rate 87% on an intention to treat analysis. The median follow-up duration was 22 months and the median overall survival was 25 months from first PV-10 treatment. Having fewer than 15 metastases at the time of treatment was associated with a complete response (P = 0.03). CONCLUSIONS: Intralesional PV-10 provided rapid lesion-specific ablation of melanoma metastases with well-tolerated local effects and minimal systemic adverse events. This therapy should be considered for patients with multiple accessible deposits within the spectrum of low to moderate disease volume.

Results of a phase II, open-label, non-comparative study of intralesional PV-10 followed by radiotherapy for the treatment of in-transit or metastatic melanoma.

BACKGROUND: In-transit and recurrent dermal or subcutaneous melanoma metastases represent a significant burden of advanced disease. Intralesional Rose Bengal can elicit tumor selective ablation and a T-cell mediated abscopal effect in untreated lesions. A subset of patients in a phase II trial setting received external beam radiotherapy to their recurrent lesions with complete or partial response and no significant acute radiation reaction. METHODS: An open-label, single-arm phase II study was performed to assess the efficacy and safety of PV-10 followed by hypofractionated radiotherapy. Patients had in-transit melanoma metastases suitable for IL therapy and radiotherapy. RESULTS: Fifteen patients were enrolled and thirteen completed both treatment components. The overall response rate was 86.6% and the clinical benefit was 93.3% on an intention to treat analysis (CR 33.3%, PR 53.3%, SD 6.7%). The median follow up duration was 19.25 months. Size of metastases (<10 mm) predicted lesion complete response (74.6%). Treatment was well tolerated with no associated grade 4 or 5 adverse events. CONCLUSIONS: The combination of PV-10 and radiotherapy resulted in lesion-specific, normal tissue-sparing, ablation of disease with minimal local or systemic adverse effects.

Primary cutaneous melanoma of the scalp: Patterns of recurrence.

INTRODUCTION: Patients with primary melanoma of the scalp have been reported to have worse disease-related outcomes compared with other anatomical regions. There are few studies in the literature specifically addressing recurrence patterns and treatment outcomes for primary scalp melanoma as a discrete anatomical sub-region. We sought to identify key features adversely influencing disease control and survival and to clarify the role of resection plane, margin, and method of reconstruction in the management of this disease process. METHODS: A retrospective clinical study of medical records was performed evaluating all patients with primary melanoma of the scalp treated at two hospitals in southeast Queensland between 2004 and 2014. RESULTS: A total of 107 patients were eligible for analysis. There were 46 recurrences in 38 patients in the cohort accounting for a recurrence rate of 35.5%. The local recurrence rate was 15.9% with 12 in-transit metastases after diagnosis. Regional and distant recurrence rates were 12.1% and 15%, respectively. At a median follow up of 30.5 months, disease-free survival was 47% and overall survival was also 47%. On multi-variate analysis, the deeper resection plane (sub-galeal) had a lower disease-free survival rate compared with the supra-galeal resection plane (P = 0.032). DISCUSSION: Our results support the hypothesis that primary scalp melanoma represents a unique aggressive subcategory with high rates of in-transit disease and poor disease-related and survival outcomes. There is a need for robust prospective comparative studies to address the significance of resection plane in the management of patients with scalp melanoma.

Muscle versus fasciocutaneous free flaps in heel reconstruction: systematic review and meta-analysis.

BACKGROUND: Management of soft tissue injuries of the heel is challenging and the composition of free tissue transfer that provides optimal aesthetic and functional outcomes in heel reconstruction is not clear. While fasciocutaneous flaps may result in shear planes that cause instability with mobilization, insensate muscle flaps may not be able to withstand the pressures of weight bearing and thus ulcerate. METHODS: A systematic literature search was performed using Medline and PubMed databases. Primary outcome measures were time to mobilize, ulceration, revision or debulking surgery, and the requirement for specialized footwear. Analysis of pooled outcomes was undertaken using fixed-effects meta-analysis, calculating the incidence rate ratio for included articles. RESULTS: Overall 576 articles were identified; out of which 11 articles met the final inclusion criteria, detailing 168 free tissue transfers in 163 patients. The study size ranged from 4 to 72 cases. There was a trend toward higher rates of ulceration (17 vs. 26%), requirement for revision (23 vs. 31%), and the requirement for specialized footwear (35 vs. 56%) in muscle flaps, but these differences were not statistically significant. CONCLUSION: The current review provided a summary of reported outcomes of free heel reconstruction in the literature till date. With the current evidence largely limited to small cohort studies (level IV evidence), there were no significant differences found between reconstructive options. These findings serve as a call to action for more reconstructive surgeons to collaborate on multi-institutional prospective studies with robust outcomes assessment. As such, an ideal flap for reconstruction of the weight-bearing heel has not yet been made clear.

Flow-through flap for salvage of fibula osseocutaneous vascular variations: a surgical approach and proposed modification of its classification.

The osseocutaneous fibula free flap is commonly used in mandibular reconstruction. Clinically important anatomic variants of the donor vessels have been reported. The authors describe a rare variant encountered while raising an osseocutaneous fibula flap. The fibula was supplied by the peroneal vessels and the overlying skin paddle was supplied by musculocutaneous perforators arising from the posterior tibial vessels. By raising 2 separate free flaps and configuring them in microvascular series with the fibula acting as a flow-through flap, the reconstruction was successful. Although the anatomic variant has been described, the authors' approach to it has not. The benefits of this method over other options include preservation of a skin paddle for monitoring and watertight oral closure and a long pedicle to the skin paddle permitting a wide arc of movement. The authors suggest a modification to the existing classification of perforators to the lateral leg skin to guide intraoperative decision making.

Radiologically derived 3D virtual models for neurosurgical planning.

Three dimensional (3D) virtual models for neurosurgery have demonstrated substantial clinical utility, especially for neuro-oncological cases. Computer-aided design (CAD) modelling of radiological images can provide realistic and high-quality 3D models which neurosurgeons may use pre-operatively for surgical planning. 3D virtual models are useful as they are the basis for other models that build off this design. 3D virtual models are quick to segment but can also be easily added to normal neurosurgical and radiological workflow without disruption. Three anatomically complex neuro-oncology cases that were referred from a single institution by three different neurosurgeons were segmented and 3D virtual models were created for pre-operative surgical planning. A face-to-face interview was performed with the surgeons after the models were delivered to gauge the usefulness of the model in pre-surgical planning. All three neurosurgeons found that the 3D virtual model was useful for presurgical planning. Specifically, the virtual model helped in planning operative positioning, understanding spatial relationship between lesion and surrounding critical anatomy and identifying anatomy that will be encountered intra-operatively in a sequential manner. It provided benefit in Multidisciplinary team (MDT) meetings and patient education for shared decision making.3D virtual models are beneficial for pre-surgical planning and patient education for shared decision making for neurosurgical neuro-oncology cases. We believe this could be further expanded to other surgical specialties. The integration of 3D virtual models into normal workflow as the initial step will provide an easier transition into modalities that build off the virtual models such as printed, virtual, augmented and mixed reality models.

Conceptualizing Scaffold Guided Breast Tissue Regeneration in a Preclinical Large Animal Model.

Scaffold-guided breast tissue regeneration (SGBTR) can transform both reconstructive and cosmetic breast surgery. Implant-based surgery is the most common method. However, there are inherent limitations, as it involves replacement of tissue rather than regeneration. Regenerating autologous soft tissue has the potential to provide a more like-for-like reconstruction with minimal morbidity. Our SGBTR approach regenerates soft tissue by implanting additively manufactured bioresorbable scaffolds filled with autologous fat graft. A pre-clinical large animal study was conducted by implanting 100 mL breast scaffolds (n = 55) made from medical-grade polycaprolactone into 11 minipigs for 12 months. Various treatment groups were investigated where immediate or delayed autologous fat graft, as well as platelet rich plasma, were added to the scaffolds. Computed tomography and magnetic resonance imaging were performed on explanted scaffolds to determine the volume and distribution of the regenerated tissue. Histological analysis was performed to confirm the tissue type. At 12 months, we were able to regenerate and sustain a mean soft tissue volume of 60.9 ± 4.5 mL (95% CI) across all treatment groups. There was no evidence of capsule formation. There were no immediate or long-term post-operative complications. In conclusion, we were able to regenerate clinically relevant soft tissue volumes utilizing SGBTR in a pre-clinical large animal model.

Limb salvage surgery reconstructive techniques following long-bone lower limb oncological resection: a systematic review and meta-analysis.

BACKGROUND: Limb salvage surgery (LSS) is now considered the gold standard surgical treatment for lower limb bone sarcomas. However, there is a paucity of literature comparing the various LSS reconstructive options. The aim of this systematic review and meta-analysis was to compare functional outcomes and complications of LSS reconstructive techniques. METHODS: The primary aim of the meta-analysis was to determine functional outcomes from the pooled data utilizing the Musculoskeletal Tumour Society score (MSTS). Comparisons could then made for this outcome between biological and prosthetic, vascularised and non-vascularised, and prosthetic and composite reconstructions. The secondary aim was to compare complication outcomes of each reconstruction. Standardized mean difference (Cohen's d) and odds ratios were estimated using a random effects model. RESULTS: Fourteen studies with a total of 785 patients were included. We found structural failure was 75% less likely to occur in prosthetic reconstruction compared to biological (OR = 0.24; 95% CI: 0.07-0.79; P = 0.02). We did not find any evidence of difference in function (MSTS score) between vascularised verses non-vascularised reconstructions (Cohen's d = -1.14; 95% CI = -3.06 to 0.78; I2  = 87%). Other analyses comparing complications found no difference between the reconstructive groups. CONCLUSION: The study found no correlation between functional outcomes and the type of LSS reconstruction. Structural failure was more likely to occur in biological when compared with prosthetic reconstruction. There was no correlation between the incidence of other complications and the type of LSS technique. This suggests a role for improved approaches to reconstruction methods including bioprinting and bioresorbable devices.

The Concept of Scaffold-Guided Bone Regeneration for the Treatment of Long Bone Defects: Current Clinical Application and Future Perspective.

The treatment of bone defects remains a challenging clinical problem with high reintervention rates, morbidity, and resulting significant healthcare costs. Surgical techniques are constantly evolving, but outcomes can be influenced by several parameters, including the patient's age, comorbidities, systemic disorders, the anatomical location of the defect, and the surgeon's preference and experience. The most used therapeutic modalities for the regeneration of long bone defects include distraction osteogenesis (bone transport), free vascularized fibular grafts, the Masquelet technique, allograft, and (arthroplasty with) mega-prostheses. Over the past 25 years, three-dimensional (3D) printing, a breakthrough layer-by-layer manufacturing technology that produces final parts directly from 3D model data, has taken off and transformed the treatment of bone defects by enabling personalized therapies with highly porous 3D-printed implants tailored to the patient. Therefore, to reduce the morbidities and complications associated with current treatment regimens, efforts have been made in translational research toward 3D-printed scaffolds to facilitate bone regeneration. Three-dimensional printed scaffolds should not only provide osteoconductive surfaces for cell attachment and subsequent bone formation but also provide physical support and containment of bone graft material during the regeneration process, enhancing bone ingrowth, while simultaneously, orthopaedic implants supply mechanical strength with rigid, stable external and/or internal fixation. In this perspective review, we focus on elaborating on the history of bone defect treatment methods and assessing current treatment approaches as well as recent developments, including existing evidence on the advantages and disadvantages of 3D-printed scaffolds for bone defect regeneration. Furthermore, it is evident that the regulatory framework and organization and financing of evidence-based clinical trials remains very complex, and new challenges for non-biodegradable and biodegradable 3D-printed scaffolds for bone regeneration are emerging that have not yet been sufficiently addressed, such as guideline development for specific surgical indications, clinically feasible design concepts for needed multicentre international preclinical and clinical trials, the current medico-legal status, and reimbursement. These challenges underscore the need for intensive exchange and open and honest debate among leaders in the field. This goal can be addressed in a well-planned and focused stakeholder workshop on the topic of patient-specific 3D-printed scaffolds for long bone defect regeneration, as proposed in this perspective review.

Protocol for the BONE-RECON trial: a single-arm feasibility trial for critical sized lower limb BONE defect RECONstruction using the mPCL-TCP scaffold system with autologous vascularised corticoperiosteal tissue transfer.

INTRODUCTION: Reconstruction of critical bone defects is challenging. In a substantial subgroup of patients, conventional reconstructive techniques are insufficient. Biodegradable scaffolds have emerged as a novel tissue engineering strategy for critical-sized bone defect reconstruction. A corticoperiosteal flap integrates the hosts' ability to regenerate bone and permits the creation of a vascular axis for scaffold neo-vascularisation (regenerative matching axial vascularisation-RMAV). This phase IIa study evaluates the application of the RMAV approach alongside a custom medical-grade polycaprolactone-tricalcium phosphate (mPCL-TCP) scaffold (Osteopore) to regenerate bone sufficient to heal critical size defects in lower limb defects. METHODS AND ANALYSIS: This open-label, single-arm feasibility trial will be jointly coordinated by the Complex Lower Limb Clinic (CLLC) at the Princess Alexandra Hospital in Woolloongabba (Queensland, Australia), the Australian Centre for Complex Integrated Surgical Solutions (Queensland, Australia) and the Faculty of Engineering, Queensland University of Technology in Kelvin Grove (Queensland, Australia). Aiming for limb salvage, the study population (n=10) includes any patient referred to the CLLC with a critical-sized bone defect not amenable to conventional reconstructive approaches, after discussion by the interdisciplinary team. All patients will receive treatment using the RMAV approach using a custom mPCL-TCP implant. The primary study endpoint will be safety and tolerability of the reconstruction. Secondary end points include time to bone union and weight-bearing status on the treated limb. Results of this trial will help shape the role of scaffold-guided bone regenerative approaches in complex lower limb reconstruction where current options remain limited. ETHICS AND DISSEMINATION: Approval was obtained from the Human Research Ethics Committee at the participating centre. Results will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ACTRN12620001007921.

Convergence of scaffold-guided bone regeneration principles and microvascular tissue transfer surgery.

A preclinical evaluation using a regenerative medicine methodology comprising an additively manufactured medical-grade ε-polycaprolactone ß-tricalcium phosphate (mPCL-TCP) scaffold with a corticoperiosteal flap was undertaken in eight sheep with a tibial critical-size segmental bone defect (9.5 cm3, M size) using the regenerative matching axial vascularization (RMAV) approach. Biomechanical, radiological, histological, and immunohistochemical analysis confirmed functional bone regeneration comparable to a clinical gold standard control (autologous bone graft) and was superior to a scaffold control group (mPCL-TCP only). Affirmative bone regeneration results from a pilot study using an XL size defect volume (19 cm3) subsequently supported clinical translation. A 27-year-old adult male underwent reconstruction of a 36-cm near-total intercalary tibial defect secondary to osteomyelitis using the RMAV approach. Robust bone regeneration led to complete independent weight bearing within 24 months. This article demonstrates the widely advocated and seldomly accomplished concept of "bench-to-bedside" research and has weighty implications for reconstructive surgery and regenerative medicine more generally.

Microsurgical anastomosis using anterior versus posterior tibial artery in lower limb free tissue transfer.

BACKGROUND: Soft tissue lower limb reconstruction often requires free tissue transfer. We investigated whether the target vessels used for micro-vascular anastomosis in the lower limb influences microsurgical outcomes. METHODS: Data from Plastic Surgery Departments of a major tertiary hospital in the United Kingdom (Leeds General Infirmary, LGI) and Australia (Princess Alexandra Hospital, PAH) were retrospectively analysed. Patients who underwent lower limb free flap reconstruction using the posterior (PTA) or anterior tibial artery (ATA) were included. Patient demographics, free flap and microvascular anastomosis details were analysed. Primary outcome was flap failure. Secondary outcome was return to theatre. RESULTS: Two hundred and thirty-four free flaps were included (PAH 115; LGI 119). 60% were muscle flaps. Eighty-one percent of patients were male, with trauma the cause in 82%. PTA was used for microsurgical anastomosis in 70% of cases. Venae comitantes were preferred (96%) for venous anastomosis. PTA group showed a higher proportion of patients with trauma as the mechanism of injury. ATA group was more likely to have an end-to-end arterial anastomosis configuration. Total flap loss was 3.8%. There was no clinically significant difference in flap failure or return to theatre using ATA versus PTA. CONCLUSIONS: Incidence of lower limb free flap failure is low (<5%) and not influenced by use of ATA versus PTA for microsurgical anastomosis. The choice of target vessels for microsurgical reconstruction of the lower limb should be predicated upon factors other than aversion to one or another vessel. If all other microsurgical considerations are equal, the surgeon can exercise personal preference.