Patient, tumour and treatment factors affect complication rates in soft tissue sarcoma flap reconstruction in a synergistic manner.

INTRODUCTION: Flap reconstruction plays an essential role in the management of soft tissue sarcoma, facilitating wide resection while maximizing preservation of function. The addition of reconstruction increases the complexity of the surgery and identification of patients who are at high risk for post-operative complications is an important part of the preoperative assessment. This study examines predictors of complications in these patients. METHODS: 294 patients undergoing flap reconstruction following sarcoma resection were evaluated. Data on patient, tumour and treatment variables as well as post-operative complications were collected. Bivariate and multivariate regression analysis was performed to identify independent predictors of complications. Analysis of synergistic interaction between key patient and tumour risk factors was subsequently performed. RESULTS: A history of cerebrovascular events or cardiac disease were found to be the strongest independent predictors of post-operative complications (OR 14.84, p = 0.003 and OR 5.71, p = 0.001, respectively). Further strong independent tumour and treatment-related predictors were high grade tumours (OR 1.91, p = 0.038) and the need for additional reconstructive procedures (OR 2.78, p = 0.001). Obesity had significant synergistic interaction with tumour resection diameter (RERI 1.1, SI 1.99, p = 0.02) and high tumour grade (RERI 0.86, SI 1.5, p = 0.01). Comorbidities showed significant synergistic interaction with large tumour resections (RERI 0.91, SI 1.83, p = 0.02). CONCLUSION: Patient, tumour and treatment-related variables contribute to complications following flap reconstruction of sarcoma defects. This study highlights the importance of considering the combined effect of multiple risk factors when evaluating and counselling patients as significant synergistic interaction between variables can further increase the risk of complications.

Reconstruction of sarcoma defects following pre-operative radiation: free tissue transfer is safe and reliable.

BACKGROUND: Neoadjuvant radiotherapy followed by surgical resection and soft tissue reconstruction provides the best possibility of achieving superior limb function in soft tissue sarcomas. The aim of this study was to report our experience of free flap microsurgical reconstruction of recently irradiated soft tissue sarcoma defects. METHODS: A retrospective study of microsurgical outcome in consecutively treated extremity and trunk sarcoma patients undergoing free tissue transfer between 2007 and 2012 was conducted from a prospectively collected database. Outcomes in pre-operatively irradiated patients were compared with non-irradiated patients. Demographic data, operative details, limb salvage rate, post-operative including microsurgical complications, and long-term limb function (Toronto Extremity Salvage score, TESS; Musculoskeletal Tumour Society Rating Scale, MSTS) were recorded and analysed for differences between the two study groups. RESULTS: Forty-six patients underwent 46 free flaps (pre-irradiated n = 32, non-irradiated n = 14) over the study period. Microvascular complications (intra-operative revision, flap re-exploration, flap loss) were uncommon and similar between the two groups (4/32 and 2/14 respectively, p > 0.05). Recipient site wound healing complications (i.e. not flap related) occurred more frequently in pre-irradiated patients (16 events) compared with the control group (2 events, p = 0.03). There was no significant difference in limb salvage rate, or TESS/MSTS functional outcome scores between the two patient groups. CONCLUSIONS: Free tissue transfer is safe and effective in patients undergoing surgical resection and reconstruction following neoadjuvant radiotherapy.

Foreskin T-cell subsets differ substantially from blood with respect to HIV co-receptor expression, inflammatory profile, and memory status.

The foreskin is the main site of heterosexual human immunodeficiency virus (HIV) acquisition in uncircumcised men, but functional data regarding T-cell subsets present at this site are lacking. Foreskin tissue and blood were obtained from Ugandan men undergoing elective adult circumcision. Tissue was treated by mechanical and enzymatic digestion followed by T-cell subset identification and assessment of cytokine production using flow cytometry. Foreskin CD4(+) T cells were predominantly an effector memory phenotype, and compared with blood they displayed a higher frequency of CCR5 expression (42.0% vs. 9.9%) and interleukin-17 production. There was no difference in T-regulatory cell frequency, but interferon-γ and tumor necrosis factor-α production were increased in foreskin CD8(+) T cells. These novel techniques demonstrate that the foreskin represents a proinflammatory milieu that is enriched for HIV-susceptible T-cell subsets. Further characterization of foreskin T-cell subsets may help to define the correlates of HIV susceptibility in the foreskin.

Medium-term cost analysis of breast reconstructions in a single Dutch centre: a comparison of implants, implants preceded by tissue expansion, LD transpositions and DIEP flaps.

BACKGROUND: Free flap breast reconstruction (BR) is generally believed to be more expensive than implant BR, but costs were previously shown to level out over time due to complications and re-operations. The aim of this study was to assess the economic implications of four BR techniques: silicone prosthesis (SP), implant preceded by tissue expansion (TE/SP), latissimus dorsi transposition with or without implant (LD ± SP) and deep inferior epigastric perforator (DIEP) flap. METHODS: A prospective historic cohort study was performed to evaluate intramural medical costs in 427 patients, who had undergone BR between 2002 and 2009. Short- and medium-term complications were incorporated. In addition, 58 patients, who had recently undergone BR, participated in a questionnaire study to prospectively evaluate extramural medical and non-medical costs. Estimates of mean short- and medium-term costs are presented per patient. RESULTS: Intramural medical costs for BR and short-term complications for unilateral DIEP flaps (€ 12,848) and TE/SP reconstructions (€ 12,400) were significantly higher than those for LD ± SP reconstructions (€ 5804), which, in turn, were more expensive than SP reconstructions (€ 4731). In bilateral cases, costs of TE/SP (€ 12,723) and LD ± SP (€ 10,760) reconstructions were comparable, while DIEP flaps (€ 15,747) were significantly more expensive and SP reconstructions were significantly cheaper (€ 6784). Overall, the medium-term costs for complications and additional operations were not significantly different (€ 3017-€ 4503). Extramural medical costs and non-medical costs were approximately € 9300 per stage, regardless of technique. CONCLUSIONS: Differences in short-term costs between techniques did not level out during follow-up and SP reconstructions remained least expensive. Single-stage SP reconstructions, however, are not suitable for all patients due to high complication rates. Definite implant placement is therefore increasingly preceded by tissue expansion at more comparable costs to autologous BR. Incorporation of non-medical costs into the cost analysis would render two-stage procedures more costly than autologous BR. To achieve the optimal result, careful patient selection is critical. Only in select cases where two options are equally applicable, cost comparison becomes a valid argument for treatment selection.

Validation of a questionnaire assessing patient's aesthetic and functional outcome after nasal reconstruction: the patient NAFEQ-score.

In determining patient satisfaction with functional and aesthetic outcome after reconstructive surgery, including nasal reconstruction, standardised assessment instruments are very important. These standardised tools are needed to adequately evaluate and compare outcome results. Since no such instrument existed for nasal reconstruction, a standardised evaluation questionnaire was developed to assess aesthetic and functional outcome after nasal reconstruction. Items of the Nasal Appearance and Function Evaluation Questionnaire (NAFEQ) were derived from both the literature and experiences with patients. The NAFEQ was validated on 30 nasal reconstruction patients and a reference group of 175 people. A factor analysis confirmed the arrangement of the questionnaire in two subscales: functional and aesthetic outcome. High Cronbach's alpha values (>0.70) for both subscales showed that the NAFEQ was an internally consistent instrument. This study demonstrated that the NAFEQ can be used as a standardised questionnaire for detailed evaluation of aesthetic and functional outcome after nasal reconstruction. Its widespread use would enable comparison of results achieved by different techniques, surgeons and centres in a standardised fashion.

The pleasing end result after DIEP flap breast reconstruction: a review of additional operations.

BACKGROUND: Breast reconstruction with deep inferior epigastric perforator (DIEP) flaps is typically a three-stage procedure, but additional operations may be required to deal with complications or to improve the aesthetic result. The purpose of this study was to evaluate the total number of operations needed after DIEP flap breast reconstruction to achieve a satisfactory end result for the patient. PATIENTS AND METHODS: From December 2002 to October 2006, 99 DIEP flap breast reconstructions obtained an end result in 72 patients. Data were collected in a structured database. Additional operations and complications were evaluated for the entire group. A study-specific questionnaire was used to evaluate patient satisfaction. RESULTS: The mean number of additional operations was 1.4 per patient. Patients with complications required more operations than patients without complications. Women who chose nipple reconstruction were younger than women who did not and were more likely to have had a primary or secondary than a tertiary reconstruction. The number of additional aesthetic operations was neither related to the occurrence of complications during the initial reconstruction, nor to patient satisfaction. Overall, patients were very satisfied with the end result. CONCLUSIONS: Completion of DIEP flap breast reconstruction involved the initial reconstruction and an average of 1.4 additional operations. Patients were generally very satisfied with the end result.

[Surgical reconstruction of large defects of the nose]. / Chirurgische reconstructie van grote defecten van de neus.

--Skin cancer of the face is the most prevalent type of cancer. The large increase of the incidence of this type of cancer in recent years has resulted in an increase of skin cancer resections in the face. --Nasal defects are the most challenging of these facial defects. Nasal reconstruction requires reconstruction of three tissue layers: the inner mucosal lining, supporting structures (cartilage or bone) and the outer cutaneous lining. --The new inner lining should consist of well-vascularized thin tissue to prevent rejection of cartilage or bone in the supporting layer. For example, septal mucosa or skin can be used in various ways to reconstruct the inner lining. --The new supporting structures, consisting of transplanted cartilage or bone, should be strong enough to prevent contraction of the soft tissues--inner and outer lining--during wound healing. --The outer lining is reconstructed per subunit of the nose, e.g. nostril, ala nasi or ridge of the nose. Usually a paramedian forehead flap is used for the reconstruction of the outer lining.

Rehabilitation after mandibular reconstruction with fibula free-flap: clinical outcome and quality of life assessment.

Tumors (benign or malignant), osteoradionecrosis or osteomyelitis sometimes lead to large segmental resections of the mandible. Osteo(cutaneous) fibula free-flaps (OFFF) are used to reconstruct these defects. New anatomical relationships as well as possible irradiation of local tissues make dental rehabilitation complicated. The aim of this study was to determine the rate of dental rehabilitation with an implant-retained lower denture or fixed appliances, after segmental resection and reconstruction of the mandible with an OFFF. Data were obtained from 70 patients, who underwent segmental mandibular resection followed by reconstruction with an OFFF, from 1995 to 2005. Dental rehabilitation was defined as a patient, who after segmental mandibular resection and reconstruction with an OFFF, received an implant-retained lower denture or fixed appliances. Clinical and functional assessments, as well as quality of life and denture satisfaction were evaluated. Twenty-four of 70 patients received dental implants; 18 received complete dental rehabilitation. Only a small percentage of patients with segmental mandibular reconstructions with an OFFF received complete dental rehabilitation, mainly because of poor survival after treatment for malignant tumors of the oral cavity. The beneficial effects of dental rehabilitation with an implant-retained denture or fixed appliances, mainly favored cosmetic aspects, rather than oral function.

Facial attractiveness and abnormality of nasal reconstruction patients and controls assessed by laypersons.

BACKGROUND: The goal of nasal reconstruction after a partial or total amputation is to achieve a nasal appearance as natural and normal as possible. It is assumed that laypersons' opinion on facial appearance could affect patient satisfaction or self-concept. The aim of this study was to assess laypersons' opinions on aesthetic outcome of nasal reconstruction. This was compared with the opinion of a professional panel. Second, the effect of informing laypersons about the previous nasal reconstruction of patients on their assessment of facial attractiveness and abnormality was studied. Third, the effects of individual facial features on the assessment of facial attractiveness and abnormality were determined. METHODS: A total of 39 consecutive patients treated between November 2001 and May 2005 for (sub) total nasal defects were included, together with a control group of 39 persons without a facial deformity. A group of 20 randomly selected laypersons (10 men and 10 women) assessed facial appearance and abnormality of all 78 persons using standardised colour slides, not knowing who was a patient and who control. Two weeks later they were informed about the true study design and the same questions were asked. In addition, they assessed final treatment results of 39 patients. RESULTS: No differences existed between assessment of aesthetic outcome after nasal reconstruction by laypersons and professionals (54% good to excellent). Patients were perceived significantly less attractive and more abnormal than controls. Prior knowledge had a significant positive effect on mean facial attractiveness and abnormality scores. High positive correlations were found between facial attractiveness and abnormality scores and the frequency of the item 'nothing in particular', meaning if no particular facial feature was judged to be striking, a face was perceived more attractive and less abnormal. CONCLUSION: Nasal reconstruction patients were perceived significantly less attractive and more abnormal by laypersons than controls. Since faces without striking features were judged to be more attractive, the goal of nasal reconstruction would not only be to create a nose as normal as possible, but also as inconspicuous as possible.

[Reconstruction of a cheek defect in three patients]. / Reconstructie wegens een wangdefect bij 3 patiënten.

A woman aged 62 and two men aged 52 and 26 all with a cheek defect following resection of a recurrence of a lentigo maligna, a recurrence of a basal-cell carcinoma of the wispy type and a dermatofibrosarcoma protuberans respectively, all underwent cheek reconstruction. The rotation flap technique was used in the first two patients. The third patient was treated with a cervicofacial musculocutaneous transposition flap and underwent postoperative radiotherapy due to the high risk of recurrence. All 3 patients made a good recovery. Defects after radical resection of malignant head and neck skin tumours can be treated by several reconstruction techniques depending on the site, size, and shape of the defect. A local transposition flap is the preferred method of reconstruction. It is important to respect the aesthetic units of the face in order to achieve the best aesthetic and functional results.

Long-term functional outcome and satisfaction after radial forearm free flap reconstructions of intraoral malignancy resections.

PURPOSE: Evaluation of objective and subjective functional follow-up results of intraoral radial forearm free flap reconstructions. METHODS: A total of 149 patients had received radial forearm free flaps between January 1996 and December 2005. Seventy-two patients completed a European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-H&N35 (EORTC H&N35) in the follow-up study. Patients were divided according to location of defect (anterior or posterior) or irradiation. Thirty-nine patients with anterior positioned flaps received standardised physical examinations. RESULTS: Flap survival was 99.3%. Complications were divided in early (<2 weeks; 23%) and late complications (20%). Most common complications were dehiscence or fistula, responding well to conservative treatment. Analysis of questionnaire subscales showed no statistically significant differences between anterior and posterior defects. Irradiation showed significant impairment for the ability to smell and taste. No important donor site impairment was found. CONCLUSION: The radial forearm free flap is an adequate method for reconstructions after resection of intraoral malignancies. Subjective functional outcome seemed to be defined by adjuvant radiotherapy, patient coping and, to a lesser extent, flap bulk for anterior defects.

Mucosal keratinocyte isolation: a short comparative study on thermolysin and dispase.

New techniques for reconstructing large defects of the floor of the mouth include the use of cultured mucosal substitutes. The purpose of this study was to compare dispase and thermolysin for keratinocyte isolation. Keratinocyte yield per surface area of rabbit buccal mucosa was assessed by histology, cytokeratin 13 (CK13) staining, seeding efficiency analysis and cell diameter quantification. Surface areas of cultured mucosa were calculated. Histology showed that treatment by thermolysin resulted in incomplete separation of epidermis from dermis. Also, the absolute number of keratinocytes/cm(2) isolated mucosa, cell yield, cell size and seeding efficiencies was higher in the dispase group. A 3.45-fold larger graft could be reconstituted using dispase. The use of dispase, rather than thermolysin, to isolate cells from buccal mucosa is concluded to be favourable.

DIEP-flap failure after pedicle division three years following transfer.

Flap neovascularisation is generally believed to make free skin-containing flaps independent of their axial pedicle blood supply. A case of DIEP-flap failure 3 years after transfer is presented in a breast reconstruction patient in whom a lateral breast reduction for symmetry improvement was performed. Causative factors in this patient were the division of the flap pedicle during lateral breast reduction and smoking in the postoperative period. A review of literature is presented and highlights the uniqueness of this case.

Primary and secondary reconstruction after surgery of the irradiated pelvis using a gracilis muscle flap transposition.

INTRODUCTION: The aim of this study is to describe our experience with reconstruction of pelvic defects after surgery for previously irradiated malignancies using a gracilis muscle flap transposition. PATIENTS AND METHODS: Between 1993 and 2002, 25 patients were treated by primary (n=7) or secondary reconstruction (n=18) using a gracilis muscle transfer. All patients were previously irradiated with a median dosage of 50 Gy. RESULTS: Direct reconstruction following resection of the tumour was accompanied with minor complications in three patients and without major complications. Median time to complete healing of the donor site and perineal defect was 11 and 46 days, respectively. Reconstruction of persistent perineal infections resulted in minor complications at the donor site (n=3) and at the perineal wound (n=11). Three patients experienced a major complication. Median time to complete healing of the donor site and perineal defect was, respectively, 17 and 190 days. Necrosis of the gracilis muscle flaps was not observed. CONCLUSION: Direct reconstruction with a gracilis transfer resulted in primary wound healing with low morbidity, hereby preventing potentially disabling persistent defects. After debridement of persistent wounds, indirect reconstruction with gracilis muscle resulted in the majority of patients in healing of the defects with acceptable morbidity.

The use of pimonidazole to characterise hypoxia in the internal environment of an in vivo tissue engineering chamber.

UNLABELLED: The distribution of hypoxic cells in an in vivo tissue engineering chamber was investigated up to 28 days post-implantation. METHODS: Arteriovenous loops were constructed and placed into bi-valved polycarbonate chambers containing 2 x 10(6) rat fibroblasts in basement membrane gel (BM gel). Chambers were inserted subcutaneously in the groin of male rats and harvested at 3 (n = 6), 7 (n = 6), 14 (n = 4) or 28 (n = 4) days. Ninety minutes before harvest, pimonidazole (60 mg/kg) was injected intraperitoneally. Chamber tissue was removed, immersion fixed, paraffin embedded, sectioned and stained immunohistochemically using hypoxyprobe-1 Mab that detects reduced pimonidazole adducts forming in cells, where pO2 < 10 mmHg. RESULTS: At 3 days a fibrin clot/BM gel framework filled the chamber. Seeded fibroblasts had largely died. The majority of 3 day chambers did not demonstrate tissue growth from the AV loop nor was pimonidazole binding present in these chambers. In one chamber in which tissue growth had occurred strong pimonidazole binding was evident within the new tissue. In four out of six 7 day chambers a broader proliferative zone existed extending up to 0.4 mm (approximately) from the AV loop endothelium which demonstrated intense pimonidazole binding. The two remaining 7 day chambers displayed even greater tissue growth (leading edge > 0.7 mm from the AV loop endothelium), but very weak or no pimonidazole binding. At 14 and 28 days the fibrin/BM gel matrix was replaced by mature vascularised connective tissue that did not bind pimonidazole. CONCLUSION: Employing a tissue engineering chamber, new tissue growth extending up to 0.4 mm from the AV loop endothelium (chambers < or = 7 days) demonstrated intense pimonidazole binding and, therefore, hypoxia. Tissue growth greater than 0.5 mm from the AV loop endothelium (7-28 days chambers) did not exhibit pimonidazole binding due to a significant increase in the number of new blood vessels and was, therefore, adequately oxygenated.

The combined free partial vastus lateralis with anterolateral thigh perforator flap reconstruction of extensive composite defects.

Myocutaneous (MC) free flaps are useful for many reconstructive indications. Perforator flaps have become standard of care. The anterolateral thigh flap (ALT) donor site is popular. With the ALT flap varying sizes of vastus lateralis (VL) muscle can be harvested as a MC flap. The skin islands of these flaps have a great range of freedom when dissected on their perforator. It was hypothesised that the VL-ALT perforator flap would offer adequate tissue volume combining maximal freedom in planning with minimal donor site morbidity. From November 2001 to February 2003 a free partial VL with ALT perforator flap was used in 11 patients to reconstruct large defects. Indications for adding a muscular component were exposed bone, skull base, (artificial) dura, or osteosynthesis material, open sinuses, and lack of muscular bulk. Flaps were planned as standard ALT flaps, after which three types of dissection were performed: I. true MC flap; II. muscle flap with a skin island on one perforator, which could be rotated up to 180 degrees ; III. chimera skin perforator flap with muscle being harvested on a separate branch from the source vessel or on a side branch of the skin perforator. Mean skin size of the MC-ALT flaps was 131 cm2. Mean muscle part size of the MC-ALT flaps was 268 cm3. Muscular parts were custom designed for all defects. No total or partial flap failures were seen. Colour mismatch was seen in 6 of 8 patients, when skin was used in the facial area in this all white population. Excessive flap bulk was found in 8 of 11 patients at 6 weeks, however, only in 2 of 11 patients after 6 months. Patients were satisfied with the functional result (8 of 11 patients) as well as the cosmetic result of their reconstruction (7 of 11 patients). All less satisfied patients had received their flap for external facial skin reconstruction. Donor site morbidity was minimal. The combined free partial VL with ALT perforator flap proved valuable as a (chimera type) MC flap with maximal freedom of planning to meet specific reconstructive demands and minimal donor site morbidity.

Flow-through anterolateral thigh flap for a free osteocutaneous fibula flap in secondary composite mandible reconstruction.

Head and neck reconstruction after tumour ablation and radiotherapy often requires complex surgery. The need for free composite tissue transfer and the poor quality of the recipient site increase the level of difficulty substantially. We report a case in which the mandible, floor of the mouth and skin of the neck needed to be reconstructed in a heavily irradiated field. A single osteocutaneous fibula flap was insufficient to reconstruct the defect, and a free anterolateral thigh (ALT) flap was also used for external neck skin resurfacing. As the recipient vessels in the ipsilateral neck had been heavily irradiated the free ALT flap was used as an interposition conduit for the free osteocutaneous fibula flap enabling it to reach the healthy recipient vessels in the contralateral neck without needing vein grafts.

Oral functional outcome after intraoral reconstruction with nasolabial flaps.

In this study, the functional and aesthetic outcome of patients with nasolabial flaps in the floor of the mouth was examined. Sixteen patients underwent reconstruction of the floor of the mouth with 19 nasolabial flaps after resection of a squamous cell carcinoma. Eight patients received postoperative radiotherapy. The patients were questioned concerning oral disabilities. Speech, mastication, deglutition, oral continence and the aesthetic result were evaluated. Two-point discrimination, temperature sensation and blunt-sharp discrimination of the intraoral flaps were tested. Speech and the wearing of dentures were hardly affected. Consumption of solid foods caused moderate problems in half of the patients. No sensibility problems were found. The aesthetic deformity was minimal. The use of nasolabial flaps in patients with limited defects of the anterior floor of the mouth after tumor resection showed adequate functional and aesthetic results.

Free flaps in the treatment of locally advanced malignancy of the scalp and forehead.

Locally advanced cutaneous malignancy of the scalp and forehead is a disease that requires an aggressive approach to resection and reconstruction. Free flap reconstruction in these sites has been advocated because of the advantages of importing large amounts of well-vascularized tissue into a recipient site, which has often been compromised by previous surgery or radiotherapy. A consecutive series of 32 free flap reconstructions in 29 patients with cutaneous malignancy of the scalp and forehead was reviewed. The flap failure rate was 6% (two flaps) and the major complication rate was 10%. Of the surviving flaps, 97% (N = 29) were successful in reconstructing a challenging group of defects. Three patients developed local recurrence of the primary malignancy (mean follow-up, 21 months). The use of a broad repertoire of free tissue transfers in reconstruction of the scalp and forehead defects has allowed effective treatment of locally advanced malignancy of this region. Critical analysis of the results, however, indicates that microsurgical reconstruction is not without morbidity and that there are refinements in the diagnostic and operative steps of management that can maximize the functional and aesthetic results.

Vascularisation of tissue-engineered grafts: the regulation of angiogenesis in reconstructive surgery and in disease states.

Angiogenesis (the formation of new blood vessels) is essential for the growth of new tissue, tissue repair and wound healing. Tissue engineering, the construction of new tissue and organs for reparative purposes, relies on angiogenesis for the vascularisation of these new grafts. In tissue engineering, the emphasis to date has been on vascularisation of newly constructed tissue grafts by an extrinsic blood supply, and relatively little attention has been given to the possibility of building these grafts around an intrinsic blood supply. However, there are many disease processes, notably tumour growth, where excess angiogenesis can be a major problem. The purposes of this review are, first, to examine various methods of vascularising tissue-engineered grafts, and, second, to compare the role of angiogenesis in tissue engineering, where stimulation of angiogenesis is paramount, with pathological states, such as tumour growth, where angiogenesis needs to be inhibited.