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.

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.

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.

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.

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.

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.

Primary leiomyosarcoma of the diaphragm.

Primary leiomyosarcoma of the diaphragm is extremely rare and only five cases have so far been reported. In the early stages clinical signs are scarce and diagnosis is difficult. The advent of MR-imaging has helped in detecting the origin of a diaphragmatic tumour and its relationship to the adjacent tissues. The highly malignant character of this tumour accounts for the poor prognosis even when radical surgery is performed.

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.

Fibrin glue in the treatment of dorsal hand burns.

This paper analyses two groups of patients with only dorsal hand burns: groups I contains patients with a total of 15 burned hands and group II patients with 12 hand burns. The patients in group I were all treated by full sheet skin grafts using a two-component fibrin glue. Patients in group II underwent the traditional operative treatment without fibrin glue and the same postoperative physical therapy programme. After follow-up periods of 6-11 months (group I) and 12-21 months (group II), we investigated in both groups, grip strength, key pinch, mobility, two-point discrimination and with the Semmes-Weinstein monofilaments. Our results prove that after the respective follow-up periods group I patients developed far better results for two-point discrimination, touch recognition and mobility.

Effect of cerium nitrate-silver sulphadiazine on deep dermal burns: a histological hypothesis.

Although there are excellent clinical results from using cerium nitrate plus silver sulphadiazine in the treatment of deep dermal burns in our burn centre, its mechanism of action remains unexplained. We set up a prospective study to establish a hypothesis which could explain the formation of the typical leathery crust. Burns treated with cerium nitrate plus silver sulphadiazine and silver sulphadiazine alone were compared histologically and metallurgically. Application of cerium nitrate plus silver sulphadiazine on deep dermal burns caused superficial connective tissue calcification with few deep dermal changes. Cerium penetration was low and silver was never detected intradermally. The precipitation of cerium and pyrophosphate destroys the calcification inhibitory function of the latter, creates multiple calcification nuclei and leads to superficial dermal calcification. No calcium was detectable in biopsies from silver sulphadiazine-treated wounds. No major toxicological side-effects were seen during this study. The clinical results were favourable, as have been reported previously.

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.

Venous congestion and blood flow in free transverse rectus abdominis myocutaneous and deep inferior epigastric perforator flaps.

A series of 240 deep inferior epigastric perforator (DIEP) flaps and 271 free transverse rectus abdominis myocutaneous (TRAM) flaps from two institutions was reviewed to determine the incidence of diffuse venous insufficiency that threatened flap survival and required a microvascular anastomosis to drain the superficial inferior epigastric vein. This problem occurred in five DIEP flaps and did not occur in any of the free TRAM flaps. In each of these cases, the presence of a superficial inferior epigastric vein that was larger than usual was noted. It is therefore suggested that if an unusually large superficial inferior epigastric vein is noted when a DIEP flap is elevated, the vein should be preserved for possible use in flap salvage. Anatomical studies with Microfil injections of the superficial venous system of the DIEP or TRAM flap were also performed in 15 cadaver and 3 abdominoplasty specimens to help determine why venous circulation (and flap survival) in zone IV of the flaps is so variable. Large lateral branches crossing the midline were found in only 18 percent of cases, whereas 45 percent had indirect connections through a deeper network of smaller veins and 36 percent had no demonstrable crossing branches at all. This absence of crossing branches in many patients may explain why survival of the zone IV portion of such flaps is so variable and unpredictable.

Use of a composite fascial carrier for laryngotracheal reconstruction.

A vascularized fascia flap may be used as a vascular carrier for free mucosal and cartilage grafts. This composite reconstruction technique has been performed in clinical situations with complex laryngeal or tracheal defects. This paper describes the technique and the rationale for applying this concept to some particular laryngotracheal defects. Morphologic and histologic aspects of this composite reconstruction technique using a transferable recipient bed are discussed.

Surgical therapy in transsexual patients: a multi-disciplinary approach.

A transsexual patient has the constant and persistent conviction that he or she belongs to the opposite sex, thus creating a deeply seated gender identity conflict. With psychotherapy being unsuccessful, it has been proven that in carefully selected patients, gender reassignment or adjusting the body to the mind (both with hormones and surgery) is the best way to normalize their lives. Optimal treatment of these patients requires the multidisciplinary approach of a gender team with the input of several specialties. Such a team consists of a nucleus of physicians who sees the patient more frequently: the psychiatrist, the endocrinologist, the plastic surgeon, the gynecologist and the urologist and a more peripheral group that sees the patients more incidentally: the psychologist, the otorhinolaryngologist, the dermatologist, the speech therapist, the lawyer, the nurse and the social worker. Between 1987 and 1999, a total of 71 male-to-female (MTF) and 54 female-to-male transsexuals have undergone gender confirming surgery in our hospital. This article gives a review and an update on the different surgical procedures as well as on the outcome in our patient population. The results in this series of patients clearly demonstrate that a close cooperation of the different surgical specialties, within our multidisciplinary gender team, is the key to success in treating transsexual patients.

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.

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.

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.