International multidisciplinary expert panel consensus on breast reconstruction and radiotherapy.

BACKGROUND: Conflicting evidence challenges clinical decision-making when breast reconstruction is considered in the context of radiotherapy. Current literature was evaluated and key statements on topical issues were generated and discussed by an expert panel at the International Oncoplastic Breast Surgery Meeting in Milan 2017. METHODS: Studies on radiotherapy and breast reconstruction (1985 to September 2017) were screened using MEDLINE, Embase and CENTRAL. The literature review yielded 30 controversial key questions. A set of key statements was derived and the highest levels of clinical evidence (LoE) for each of these were summarized. Nineteen panellists convened for dedicated discussions at the International Oncoplastic Breast Surgery Meeting to express agreement, disagreement or abstention for the generated key statements. RESULTS: The literature review identified 1522 peer-reviewed publications. A list of 22 key statements was produced, with the highest LoE recorded for each statement. These ranged from II to IV, with most statements (11 of 22, 50 per cent) supported by LoE III. There was full consensus for nine (41 per cent) of the 22 key statements, and more than 75 per cent agreement was reached for half (11 of 22). CONCLUSION: Poor evidence exists on which to base patient-informed consent. Low-quality studies are conflicting with wide-ranging treatment options, precluding expert consensus regarding optimal type and timing of breast reconstruction in the context of radiotherapy. There is a need for high-quality evidence from prospective registries and randomized trials in this field.

ANTECEDENTES: El hecho de que la evidencia disponible sea conflictiva supone un reto para la toma de decisiones a la hora de considerar la reconstrucción mamaria en el contexto de radioterapia (radiotherapy, RT). En el seno de un panel de expertos reunidos durante el International Oncoplastic Breast Surgery Meeting celebrado en Milán en 2017, se revisó la literatura disponible y se generaron y discutieron los aspectos más relevantes. MÉTODOS: Se hizo una búsqueda bibliográfica de los estudios de RT y reconstrucción mamaria (1985-septiembre de 2017) en las bases MEDLINE, EMBASE y CENTRAL. La revisión de la literatura permitió identificar 30 cuestiones clave controvertidas. A partir de ellas, se construyeron una serie de afirmaciones, para las que se obtuvo el mayor nivel de evidencia (levels of clinical evidence, LoE) posible. El acuerdo, desacuerdo o abstención respecto a las cuestiones propuestas fueron el resultado de las discusiones de 19 expertos reunidos durante el International Oncoplastic Breast Surgery Meeting. RESULTADOS: Se identificaron 1.522 artículos publicados en revistas con peer review. Se elaboró una lista de 22 afirmaciones clave y se anotó el LoE más alto obtenido para cada una de ellas. El grado de variabilidad fue de II a IV, pero la mayoría de las afirmaciones (54,5%) obtuvieron un LoE III. Hubo un consenso total en el 41% (9/22) de las afirmaciones, mientras que se obtuvo más de un 75% de acuerdo en la mitad de las afirmaciones (11/22). CONCLUSIÓN: La evidencia en la que basar el consentimiento informado en estos pacientes es escasa. Se trata de estudios de baja calidad con gran variedad de opciones terapéuticas, que dificultan el consenso de los expertos acerca del tipo y momento óptimo para la reconstrucción mamaria en el contexto de RT. Para obtener datos de mayor calidad se precisan estudios prospectivos y ensayos clínicos en este campo.

Soft tissue fillers for adipose tissue regeneration: From hydrogel development toward clinical applications.

There is a clear and urgent clinical need to develop soft tissue fillers that outperform the materials currently used for adipose tissue reconstruction. Recently, extensive research has been performed within this field of adipose tissue engineering as the commercially available products and the currently existing techniques are concomitant with several disadvantages. Commercial products are highly expensive and associated with an imposing need for repeated injections. Lipofilling or free fat transfer has an unpredictable outcome with respect to cell survival and potential resorption of the fat grafts. Therefore, researchers are predominantly investigating two challenging adipose tissue engineering strategies: in situ injectable materials and porous 3D printed scaffolds. The present work provides an overview of current research encompassing synthetic, biopolymer-based and extracellular matrix-derived materials with a clear focus on emerging fabrication technologies and developments realized throughout the last decade. Moreover, clinical relevance of the most promising materials will be discussed, together with potential concerns associated with their application in the clinic.

Composite breast reconstruction: Implant-based breast reconstruction with adjunctive lipofilling.

INTRODUCTION: Options for breast reconstructions enclose autologous tissue transfers or implants. Fat grafting is gaining more interest in this specific field of breast surgery. This study concentrates on the technique and aesthetic results of breast reconstruction with fat grafts combined with implants, in women who have undergone total mastectomy. METHODS: Breast reconstructions (n = 23) was performed using a protocol of intratissular expansion with serial deflation-lipofilling. In order to achieve the best aesthetic outcome, an additional small implant was placed. A retrospective data analysis was performed. In all patients a tissue expander was placed at the time of mastectomy or after removal of a previous breast reconstruction. The mean of lipoaspirate material for the reconstruction was 333 mL (range 120-715 mL). To create an adequate volume of the reconstructed breast, a supplementary small implant was placed, with a mean volume of 222 mL (range 125-375 mL). The mean follow-up was 33 months (range 19-50 months). RESULTS: A MRI analysis was performed in eight patients at least 9 months after the last lipofilling procedure, demonstrating a mean of 171 mL (range 64-538 mL) of transferred fat, a mean fat survival of 53% and a volume ratio of fat graft/implant of 0.97 (range 0,3-3,8). CONCLUSION: This composite technique of using autologous fat tissue and implants shows aesthetic pleasant results and must be considered as a valid alternative in a subset of patients. Further investigations to optimize the fat graft take must be encouraged.

An international comparison of reimbursement for DIEAP flap breast reconstruction.

INTRODUCTION: The deep inferior epigastric artery perforator (DIEAP) flap is currently considered the gold standard for autologous breast reconstruction. With the current economic climate and health cutbacks, we decided to survey reimbursement for DIEAP flaps performed at the main international centres in order to assess whether they are funded consistently. METHODS: Data were collected confidentially from the main international centres by an anonymous questionnaire. RESULTS: Our results illustrate the wide disparity in international DIEAP flap breast reconstruction reimbursement: a unilateral DIEAP flap performed in New York, USA, attracts €20,759, whereas the same operation in Madrid, Spain, will only be reimbursed for €300. Only 35.7% of the surgeons can set up their own fee. Moreover, 85.7% of the participants estimated that the current fees are insufficient, and most of them feel that we are evolving towards an even lower reimbursement rate. In 55.8% of the countries represented, there is no DIEAP-specific coding; in comparison, 74.4% of the represented countries have a specific coding for transverse rectus abdominis (TRAM) flaps. Finally, despite the fact that DIEAP flaps have become the gold standard for breast reconstruction, they comprise only a small percentage of all the total number of breast reconstruction procedures performed (7-15%), with the only exception being Belgium (40%). CONCLUSION: Our results demonstrate that DIEAP flap breast reconstruction is inconsistently funded. Unfortunately though, it appears that the current reimbursement offered by many countries may dissuade institutions and surgeons from offering this procedure. However, substantial evidence exists supporting the cost-effectiveness of perforator flaps for breast reconstruction, and, in our opinion, the long-term clinical benefits for our patients are so important that this investment of time and money is absolutely essential.

Facial transplantation: history and update.

BACKGROUND: Composite tissue allografting (CTA) represents the essence of reconstructive surgery, combining principles of solid organ transplantation (SOT) and modern plastic surgery techniques. The purpose of this article is to give a review of the history of facial CTA and an update of the cases that have been operated so far worldwide. METHODS: A systematic review of the medical literature was performed. Ten relevant publications were selected and analyzed for clinical data of the patients, surgical aspects of transplantation, complications and outcome. RESULTS: The past 9 years, 31 face transplants have been performed worldwide. The main indication was posttraumatic deformity. In all cases standard triple drug immunosuppression as used in SOT was successfully used and at least 1 period of acute rejection was seen in all patients, controllable with conventional immunosuppressive regimens. Overall functional outcomes are good and satisfaction rate is high, surpassing initial expectations. The main complications are opportunistic infections; 4 deaths occurred. CONCLUSIONS: Facial CTA is a life changing procedure and has led to new treatment options for patients with complex, devastating and otherwise unreconstructable facial deformities to restore appearance and overall wellbeing in a single operation. The key to success lies in the selection of the appropriate patient, who is stable, well-motivated and therapy compliant. Thorough screening and follow-up by a multidisciplinary team, well prepared surgical approach and intensive, early rehabilitation are all crucial factors for minimizing complications and a safe and rapid recovery.

Phase III development of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire module for women undergoing breast reconstruction.

BACKGROUND: Comprehensive outcome assessments after breast reconstruction (BRR) require surgery-specific patient-reported outcome measures. The aims of this study were to assess the relevance, acceptability and redundancy of questions/items (phase III pretesting) of a new BRR questionnaire evaluating patients' health-related quality of life before and after BRR. Phase III occurred in collaboration with the European Organization for Research and Treatment of Cancer (EORTC) following earlier development phases that identified 31 items. METHODS: The EORTC BRR subgroup applied decision-making rules to each question according to eight EORTC criteria. A total of 197 patients (from the UK, Austria, Belgium, Italy and Sweden) were recruited. Forty-seven patients completed pre- and post-BRR questionnaires prospectively, and 150 reported post-BRR questionnaires only retrospectively. Qualitative debriefing interviews were undertaken in 189 patients. Preliminary psychometric analyses were performed. RESULTS: Thirty-one items fulfilled 'relevance', with none producing 'difficulties'. Ten items were not a priority for 10 per cent of respondents. Of these, two questions concerning muscle twitching in the affected breast and problem with donor-site swelling were deleted. Three redundant items were deleted: weakness in arm, which correlated significantly to the Quality of Life Questionnaire (QLQ) BR23 breast questionnaire, and shape and colour of the affected nipple. Descriptive statistics reduced the module to 26 items conceptualized into three provisional scales (disease treatment/surgery-related symptoms, sexuality and cosmetic outcome) within the newly completed questionnaire, EORTC QLQ-BRR26. CONCLUSION: The QLQ-BRR26 is available for psychometric validation in a large-field international sample. The intended use for QLQ-BRR26 is alongside EORTC QLQ-C30 and QLQ-BR23, in women treated by mastectomy for breast cancer and undergoing all types of BRR.

LC-MS profiling of N-alkylamides in Spilanthes acmella extract and the transmucosal behaviour of its main bio-active spilanthol.

N-Alkylamides are a promising group of naturally occurring bio-actives, with evidence for immune stimulating properties, which find applications i.a. in buccal preparations. In Spilanthes extracts, these properties are mainly ascribed to the most abundant N-isobutylamide, spilanthol. Yet, other N-alkylamides present in these extracts may contribute to this effect, as well as to its potential toxicity and physiologic interactions. Therefore, N-alkylamide profiling of an ethanolic Spilanthes extract was performed using a gradient reversed phase high performance liquid chromatography/electrospray ionization ion trap mass spectrometry (HPLC/ESI-MS) method on an embedded polar column. MS(1) and MS(2) fragmentation data were used for identification purposes. Moreover, the transmucosal behaviour of spilanthol, formulated in this ethanolic extract and in two commercially available oral gels, was evaluated using porcine buccal mucosa in a Franz diffusion cell experimental set-up. A high-throughput HPLC-UV method was used for the quantification of spilanthol in the receptor phase. Fundamental permeation characteristics of spilanthol in a solvent-independent way (100% aqueous dose solution) were obtained using different propylene glycol/water ratios. Eight N-isobutylamides, two 2-methylbutylamides and one 2-phenylethylamide were detected, with spilanthol as most abundant N-alkylamide (88.8%). Up till now, two of these N-isobutylamides were not yet described in Spilanthes extracts. We demonstrated for the first time that spilanthol permeates the buccal mucosa. Depending on the formulation, a more pronounced local or systemic effect is achieved, which is important for the regulatory product classification. The purely aqueous permeation coefficient K(p,aq) (+/-SEM) was found to be 11.3 (+/-0.403)10(-3)cm/h.

Necrotizing fasciitis complicated by fatal multiple organ dysfunction due to Pasteurella multocida infection: a case report.

Necrotizing fasciitis is rarely caused by Pasteurella multocida, a facultative anaerobic gram-negative coccobacillus found in the flora of the oro-gastrointestinal tract of many animals. We describe a rare case with overwhelming septicaemia resulting in multiple organ failure.

The inframammary extending lateral intercostal artery perforator flap for reconstruction of axillary contractures: a case report.

SUMMARY: Release and reconstruction of axillary scar contractures can be challenging due to the specific anatomic site and contouring of the axillary region. Pliable and unscarred skin coverage of resulting defects after scar release is needed which enhances the postoperative recovery and revalidation. When traditional donor regions of fasciocutaneous flaps are involved in the scarred area, options are few. We describe the design and versatility of an inframammary extended lateral intercostal artery perforator (LICAP) flap to reconstruct an axillary defect after wide scar release and debridement. The postoperative recovery was uneventful with restoration of the range of motion of the shoulder joint.

Human clinical experience with adipose precursor cells seeded on hyaluronic acid-based spongy scaffolds.

Histioconductive approaches to soft-tissue defects use scaffolds seeded with lineage- and tissue-specific progenitors to generate tissue which should reside in equilibrium with adjacent tissue. Scaffolds guide histiogenesis by ensuring cell-cell and cell-matrix interactions. Hyaluronic acid-based (HA) preadipocyte-seeded scaffolds were evaluated for their adipo-conductive potential and efficacy in humans. Preadipocytes were isolated from lipoaspirate material and seeded on HA scaffolds. The cellular bio-hybrid (ADIPOGRAFT) and an acellular control scaffold (HYAFF11) were implanted subcutaneously. At specific time points (2, 8 and 16 weeks) explants were analyzed histopathologically with immunohistochemistry. No adverse tissue effects occurred. Volume loss and consistent degradation of the HYAFF11 scaffolds compared to the ADIPOGRAFT group indicated progressive tissue integration. No consistent histological differences between both groups were observed. By 8 weeks all void spaces within the scaffolds were filled with cells with pronounced matrix deposition in the ADIPOGRAFT bio-hybrids. Here we show that HA scaffolds were stable cell carriers and had the potential to generate volume-retaining tissue. However, no adipogenic differentiation was observed within the preadipocyte-seeded scaffolds.

Comparing the cost of delayed and immediate autologous breast reconstruction in Belgium.

This study documents the cost of immediate and delayed DIEP flap breast reconstruction. Immediate reconstruction is more attractive from an economic perspective since it only requires one operation, one anaesthetic procedure and one recovery period in hospital. From the perspective of healthcare budget management, assessing the possible cost savings from immediate reconstruction yields interesting results. Since charges do not reflect the real costs of providing care, we calculated resource costs using the micro-costing method. About 95% of the initial mastectomy costs could be saved when performing an immediate breast reconstruction. This was about 35% of total standard direct and indirect costs due to mastectomy and delayed breast reconstruction. In a growing cost conscious environment of managed care, the economic evaluation should, therefore, encourage the trend towards more immediate reconstructions.

Do pre-operative abdominal exercises prevent post-operative donor site complications for women undergoing DIEP flap breast reconstruction? A two-centre, prospective randomised controlled trial.

The deep inferior epigastric perforator (DIEP) flap is the gold standard for breast reconstruction using abdominal tissue. Unlike the transverse rectus abdominis myocutaneous (TRAM) flap, no rectus abdominis muscle is removed with the flap, but intra-muscular scarring can still cause post-operative complications. Strong abdominal muscles have been advocated as a prerequisite for surgery, but without any evidence as to the potential benefits. This study aimed to investigate the effect of pre-operative abdominal exercises on inpatient pain levels, length of hospital stay, post-operative abdominal muscle strength and function following a DIEP flap.Ninety-three women undergoing delayed breast reconstruction with a DIEP flap between October 1999 and November 2000 were randomly allocated to either a control or exercise group. The exercise group performed pre-operative exercises using the Abdotrim abdominal exerciser. Pre-operatively, outcome measures included trunk muscle strength measured on an isokinetic dynamometer, SF-36, rectus muscle thickness measured using ultrasound, and submaximal fitness. Post-operative pain and length of hospital stay were recorded. Subjects were reassessed using the same outcome measures 1 year post-operatively. There was a statistically significant increase in static (isometric) muscle strength and thickness pre-operatively for the exercise group. One year following surgery, there was a significant decrease in dynamic (concentric and eccentric) flexion strength for both groups, although the clinical significance of this is questionable as the majority of women had returned to pre-operative fitness and the surgery had no impact on functional activities. The static flexion strength of the control group was reduced at 1 year, whereas it was maintained in the exercise group, although this was not statistically significant. One third of women in the control group complained of functional problems or abdominal pain post-operatively compared to one fifth of the exercise group. Overall, the DIEP flap had no major impact on abdominal muscle strength for either group, demonstrating its superiority over the TRAM flap. There was no statistically significant benefit to the exercise group of the pre-operative exercises 1 year following surgery. However, there was a subjective benefit, albeit statistically nonsignificant, in terms of reduced functional problems post-operatively and improved well-being prior to surgery.

The effect of ultrasound-assisted liposuction and conventional liposuction on the perforator vessels in the lower abdominal wall.

Scientific reports of clinical in vivo research into the effects and side-effects of ultrasonic-assisted liposuction (UAL) are scarce. Advocates of UAL claim that the damage to vascular and nervous structures is limited and even less than with conventional and/or tumescent liposuction (CL). The effect of tumescent infiltration alone and combined with either CL or UAL was assessed by performing injection studies of the panniculus adiposus of the lower abdominal wall of 20 fresh cadavers and five abdominoplasty specimens. Besides the control and infiltration groups (n=5 in each), there was an additional group of ten cadaver flaps and five abdominoplasty flaps that underwent infiltration followed by UAL in the right half of the flap and infiltration followed by CL in the left half of the flap. Radiographs of these flaps were shown to a blinded panel of ten plastic surgeons, who were asked to evaluate and compare the damage on the basis of the number and magnitude of contrast-medium extravasations in the flap. Vascular damage to the perforating vessels was seen even after infiltration alone, although it was very limited. A variable amount of damage (ranging from little to extensive) was observed in the CL and UAL groups. Statistical analysis of the judgments of the observers could not show that either technique was less damaging than the other. UAL is, therefore, probably more beneficial to the surgeon than to the patient. The financial investment in the device is justified for surgeons with large liposuction practices, mainly, and probably solely, because of the reduced physical strain for the surgeon.

Different responses to preoperative chemotherapy for invasive lobular and invasive ductal breast carcinoma.

AIM: Preoperative chemotherapy (PCT) is used in primary breast cancer, to facilitate breast conservative surgery (BCS). Clinical and pathologic responses are important prognostic parameters. Biologic markers are needed to individualize treatment. PATIENTS AND METHODS: One hundred and thirty-five patients with breast carcinoma were treated with PCT, followed by surgery and adjuvant therapy. Clinical response and pathological complete response (pCR), biological markers and type of surgery were compared between invasive ductal (IDC) and invasive lobular carcinoma (ILC). RESULTS: Overall response (OR) for IDC was 75% compared to 50% for ILC (P=0.0151). Pathological CR was 15% for IDC and 0% for ILC (P=0.0066). Fifty-six percent of the responding patients had BCS, in contrast with 16% of the non-responders. BCS was performed in 50% of patients with IDC, in 38% of the patients with ILC. Salvage surgery was more necessary in ILC (19%) compared to IDC (4%) (P=0.0068). Patients with ILC were more frequently ER-positive and HER-2 negative than patients with IDC. CONCLUSIONS: Clinical and pathological responses are lower in ILC compared to IDC. After PCT, patients with large ILC should preferably be offered mastectomy with immediate breast reconstruction. However, PCT still remains valuable to evaluate tumor response and biologic factors in vivo.

A conservative approach for deep dermal burn wounds using polarised-light therapy.

This article reports a clinical study investigating the role of polarised-light therapy in the conservative treatment of deep dermal burn wounds. In 22 out of 67 patients with deep dermal burn wounds, clinical evaluation revealed only a very limited potential for spontaneous healing, and, despite the fact that the majority of the surgeons (four out of six) would have recommended surgery, these patients were treated conservatively with polarised-light therapy (400-2000 nm, 40 m W cm(-2), 2.4 J cm(-2)) until complete closure. Evaluation by a panel of four surgeons, all experts in burn surgery, revealed that conservative treatment of these deep dermal wounds with polarised-light irradiation resulted in a significantly shorter healing time, with almost no hypertrophic scarring, and optimal aesthetic and functional results at long-term follow-up. No extension of the hospital stay was required. Polarised-light therapy may be a valuable way of avoiding surgery in patients with deep dermal burns.

Ischial pressure sore reconstruction using an inferior gluteal artery perforator (IGAP) flap.

Perforator-flap technique has revolutionised the practice of free tissue transfer with the goal of muscle sparing for function and strength. These concepts are being widely explored for breast reconstruction. The field of pressure-sore reconstruction presents a new application for this technique, preserving muscle for function in ambulatory patients and for future reconstruction in paraplegic patients. Just as the superior gluteal artery perforator flap holds promise for sacral and trochanteric reconstruction, the inferior gluteal artery perforator flap may provide a muscle-sparing alternative for ischial reconstruction. A case report of the successful use of an inferior gluteal artery perforator flap for ischial pressure-sore reconstruction is described, including the surgical technique employed for flap harvest, and 2 year's follow-up.

Complete survival of a free flap after early pseudoaneurysm formation and pedicle thrombosis.

A microsurgical pseudoaneurysm is a very rare complication after free flap surgery. The authors report a case of a free thoracodorsal artery perforator flap transferred to a degloving wound on the dorsum of the foot and ankle. The patient developed pedicle thrombosis caused by a septic pseudoaneurysm, which was treated by conservative means. Sufficient vascularization developed within 15 days after surgery and the flap survived completely. This is in sharp contrast to other reported cases of pseudoaneurysm formation, all of which were treated surgically and resulted in flap failure, except in one case. A critical review of the literature is presented and the factors influencing flap survival are discussed.

The versatility of the pudendal thigh fasciocutaneous flap used as an island flap.

The pudendal thigh flap is a sensate fasciocutaneous flap based on the terminal branches of the superficial perineal artery, which is a continuation of the internal pudendal artery. Several authors have reported using this axial patterned flap in a bilateral fashion to reconstruct the vagina, mostly in patients with vaginal atresia. The technique is simple, safe, and reliable, and no stents or dilators are required. The reconstructed vagina has a natural angle and is sensate. The donor site in the groin can be closed primarily with an inconspicuous scar. The distinct advantages of this flap widen its indications to several other pathologies. In this article, the authors report on the bilateral use of the flap to reconstruct a vagina in patients with congenital atresia (n = 8) and after oncological resection (n = 5). Furthermore, the versatility of this island flap is also demonstrated by its use in a unilateral fashion in patients with recurrent or complex rectovaginal fistulas (n = 4) and in two patients with a defect of the posterior urethra in a heavily scarred perineum. All 31 pudendal thigh flaps survived completely. Some wound dehiscence was observed in two patients. Two other patients required a minor correction at the introitus of the vagina. The functional outcome was excellent in all patients, despite the presence of some hair growth in the flaps. This article discusses the expanding indications of this versatile flap and the refinements in operative technique.