Bien Keem Tan

Skin tissue engineering advances in severe burns: review and therapeutic applications

Current advances in basic stem cell research and tissue engineering augur well for the development of improved cultured skin tissue substitutes: a class of products that is still fraught with limitations for clinical use. Although the ability to grow autologous keratinocytes in-vitro from a small skin biopsy into sheets of stratified epithelium (within 3 to 4xa0weeks) helped alleviate the problem of insufficient donor site for extensive burn, many burn units still have to grapple with insufficient skin allografts which are used as intermediate wound coverage after burn excision. Alternatives offered by tissue-engineered skin dermal replacements to meet emergency demand have been used fairly successfully. Despite the availability of these commercial products, they all suffer from the same problems of extremely high cost, sub-normal skin microstructure and inconsistent engraftment, especially in full thickness burns. Clinical practice for severe burn treatment has since evolved to incorporate these tissue-engineered skin substitutes, usually as an adjunct to speed up epithelization for wound closure and/or to improve quality of life by improving the functional and cosmetic results long-term. This review seeks to bring the reader through the beginnings of skin tissue engineering, the utilization of some of the key products developed for the treatment of severe burns and the hope of harnessing stem cells to improve on current practice.

Targets of genome copy number reduction in primary breast cancers identified by integrative genomics

The identification of specific oncogenes and tumor suppressor genes in regions of recurrent aneuploidy is a major challenge of molecular cancer research. Using both oligonucleotide single‐nucleotide polymorphism and mRNA expression arrays, we integrated genomic and transcriptional information to identify and prioritize candidate cancer genes in regions of increased and decreased chromosomal copy number in a cohort of primary breast cancers. Confirming the validity of this approach, several regions of previously‐known copy number (CN) alterations in breast cancer could be successfully reidentified. Focusing on regions of decreased CN, we defined a prioritized list of eighteen candidate genes, which included ARPIN, FBN1, and LZTS1, previously shown to be associated with cancers in breast or other tissue types, and novel genes such as P29, MORF4L1, and TBC1D5. One such gene, the RUNX3 transcription factor, was selected for further study. We show that RUNX3 is present at reduced CNs in proportion to the rest of the tumor genome and that RUNX3 CN reductions can also be observed in a breast cancer series from a different center. Using tissue microarrays, we demonstrate in an independent cohort of over 120 breast tissues that RUNX3 protein is expressed in normal breast epithelium but not fat and stromal tissue, and widely down‐regulated in the majority of breast cancers (>85%). In vitro, RUNX3 overexpression suppressed the invasive potential of MDA‐MB‐231 breast cancer cells in a matrigel assay. Our results demonstrate the utility of integrative genomic approaches to identify novel potential cancer‐related genes in primary tumors. This article contains Supplementary Material available at http://www.interscience.wiley.com/jpages/1045‐2257/suppmat.

Optimizing the use of local muscle flaps for knee megaprosthesis coverage.

Primary muscle flap cover of megaprostheses following limb salvage surgery for tumors around the knee serves to decrease infection rates, provide additional soft tissue cover over the implant, and act as a bed for split-skin grafting. The purpose of this study is to demonstrate the role of supplementary muscle flaps such as the hemisoleus, gracilis, and semimembranosus in augmenting coverage provided by gastrocnemius muscle flaps. Between August 1999 and August 2006, 10 patients underwent resection of distal femur (n = 5) or proximal tibia (n = 5) sarcomas, followed by bone reconstruction with a modular megaprosthesis and soft tissue coverage with local pedicled flaps. The average age was 31 years (range, 13 to 47), with pathologic diagnoses inclusive of osteosarcoma (n = 7), chondrosarcoma (n = 2), and recurrent giant cell tumor (n = 1). For proximal tibial tumors, both bellies of the gastrocnemius with hemisoleus for additional soft tissue cover were used. For distal femoral tumors, 1 gastrocnemius belly sutured to the extensor mechanism and gracilis or semimembranosus provided adequate soft tissue cover. All flaps survived without complications, all wounds healed well, and all patients were ambulant after surgery. The role of supplementary muscle flaps was demonstrated in specific situations, where coverage of the subcutaneous area of the midtibia was deficient and where a significant amount of the vastus medialis or gastrocnemius has been resected. Technical refinements included primary skin grafting to relieve tension during skin closure and excision of the aponeurosis over the gastrocnemius and hemisoleus to increase the reach and surface area of the muscle flap.

In Vivo Tissue Engineering Over Wounds With Exposed Bone and Tendon: Autologous Dermal Grafting and Vacuum-assisted Closure

Flap coverage is ideal for wounds exposing bone and tendon, but technically less demanding and speedier options might be considered for small shallow wounds and for wounds with adjacent tissue loss precluding local flaps. We revisited the use of autologous dermal grafting-in combination with vacuum-assisted closure (VAC)-for such wounds.Five small- to medium-sized wounds exposing bone, joint, and/or tendon were each covered using an autologous meshed dermal graft followed by VAC application to induce granulation. Closure was completed at 2 weeks by split-thickness skin grafting over the granulating dermis graft.Complete and stable wound healing was achieved in all cases within 4 weeks of dermal grafting over exposed bone with excellent outcome at 1 year in terms of donor site healing and return to function. All healed wounds had a nearly flush profile with no bulkiness in the foot and toe region.Autologous dermal grafting with VAC is an integrated in vivo tissue engineering system in which the meshed dermis acts as an attractive scaffold for granulation within the conducive VAC-medium. As an alternative to flap surgery or dermal substitutes, the technique is simple, swift, and cost-effective for immediate closure of small shallow wounds and even multiple small wounds, exposing bone and tendon particularly in the lower legs, feet, and toes.

Use of the microdebrider for treatment of fibrous gynaecomastia.

BACKGROUNDnIn the quest for reduced scars and better aesthetic outcomes in minimally invasive surgical techniques for gynaecomastia, suction-assisted lipoplasty and ultrasound-assisted lipoplasty are now considered accepted recent advancements. Nevertheless, the fibrous glandular breast disc encountered in young, thin patients requires a separate peri-areolar incision as the disc cannot be removed with suction lipoplasty. The use of a microdebrider (powered shaving rotary device) is a potential solution to this problem. We present a series of eight patients with fibrous gynaecomastia that was successfully treated in this way.nnnMETHODnThe surgery is performed under general anaesthesia. The microdebrider cannula is used to remove the fibrous glandular breast tissue. Drains are inserted and fibrin glue is sprayed subcutaneously. Patients are discharged on the next day. Drains are removed on the 5th postoperative day. A compressive vest is worn for 6 weeks. (A video of the procedure can be seen on http://www.microflap.com/video3.asp).nnnRESULTSnThe eight patients were successfully treated. No bleeding, haematoma or seroma was encountered. All patients were satisfied with the results of the surgery.nnnCONCLUSIONnThe microdebrider is a viable solution in the treatment of gynaecomastia with a fibrous breast disc. Excellent aesthetic results can be achieved with a single 3-mm incision.

Aesthetic Design of Skin-Sparing Mastectomy Incisions for Immediate Autologous Tissue Breast Reconstruction in Asian Women

Background The advent of skin-sparing mastectomy has allowed for the reconstruction of the breast and nipple with improved cosmesis. However, the nipple-areolar complex (NAC) in Asian patients is more pigmented and scars easily. Therefore, commonly described incisions tend to result in poor aesthetic outcomes in Asian patients with breast cancer. Methods We describe an algorithmic approach to skin-sparing mastectomy incisions in Asian patients on the basis of the location of the biopsy scar and the tumor site and size. Four incision types are described: peri-areolar, a peri-areolar incision with a second distant skin paddle, racquet handle, and peri-areolar with adjacent skin excision. Results 281 immediate breast reconstructions were performed between May 2001 and February 2012 after skin-sparing mastectomy. The mastectomy incisions used included the peri-areolar design (n=124, 44%), peri-areolar design with a second distant skin paddle (n=39, 14%), racquet handle (n=21, 7.5%), and peri-areolar design with adjacent skin excision (n=42, 14%). The traditional elliptical incision and other variants where the NAC outline was not preserved were performed in the remaining 55 patients. The average follow-up was 44.7 months during which there was 1 case of total flap loss and 7 cases of partial flap necrosis; all remaining flaps survived. 24% of the patients (68/281) underwent subsequent nipple reconstruction. Conclusions Our algorithm avoids breast incisions that are randomly placed or excessively long and prevents the unnecessary sacrifice of normal breast skin. This allows skin-sparing mastectomy and immediate breast reconstruction to be performed with a consistently achievable aesthetic result in Asian women without neglecting oncological safety.

Burns infection profile of Singapore: prevalence of multidrug-resistant Acinetobacter baumannii and the role of blood cultures

BackgroundWith various changes implemented such as perioperative antibiotics for tangential excision, this retrospective study reviews the infection profile of burn patients at Singapore’s only centralized burns unit. Worldwide, the appearance of multidrug-resistant (MDR) strains of Acinetobacter baumannii (A. baumannii) continues to worsen patient outcomes. This study also surveys the role of blood cultures in burns at our unit.MethodsFour hundred fifty-two burn patients admitted to the unit between 2011 and 2013, and with cultures performed, were included in the study. The yields of various cultures were evaluated and 2684 samples were amassed, of which 984 (36.7xa0%) were positive. Patient variables for predictors of MDR A. baumannii infection acquisition and bacteremia were evaluated through multivariate analyses.ResultsPseuodomonas aeruginosa (P. aeruginosa) (67 patients) was the most common organism in those with total body surface area (TBSA)xa0burn <20xa0% while MDR A. baumannii (39 patients) was most prevalent in those with TBSAxa0burn ≥20xa0%. We found a yield of 1.1xa0% positive blood cultures for TBSA burn <20xa0% and a yield of 18.6xa0% positive cultures in TBSA burn ≥20xa0%. The median time between surgery and bacteremia was 6.5xa0days (range -18 to 68xa0days, interquartile range 4.5); 2.9 and 8.8xa0% of bacteremic episodes occurred within 24 and 48xa0h, respectively. This is a decrease from a predeceasing study (45.3xa0% for 24xa0h and 60xa0% for 48xa0h). Multivariate analysis revealed that length of hospital stay and TBSAxa0burn ≥20xa0% were predictors of MDR A. baumannii infection and positive blood cultures.ConclusionsMDR A. baumannii infection burdens patient management, especially in those with TBSAxa0burn ≥20xa0% and longer hospital stay. Prophylactic antibiotics may reduce perioperative bacteremia, but their role in MDR infections needs to be evaluated. The role of blood cultures in TBSAxa0burn <20xa0% needs reconsideration.

The trends of burns epidemiology in a tropical regional burns centre

INTRODUCTIONnSingapore General Hospital (SGH) is a regional burns centre in Southeast Asia and is the only dedicated burns facility providing specialized burns care in Singapore.nnnMETHODSnA cohort study was performed for burns patients admitted to SGH from 2011 to 2013. We compared our data with earlier studies and observed the trends of burns epidemiology in Singapore. Results were analyzed using the SPSS programme.nnnRESULTSn655 patients were admitted during this study period, a 35.9% increase from 2003 to 2005. Scalding by water and flame injury remain the top causes of burns and the mean extent of burn is 9.5%. TBSA correlates with the incidence of burn infection, bacteremia and mortality. Patients with ≥20% TBSA are at a higher risk of bacteremia, and ≥ 34% TBSA is a predictor of mortality. 4.9% (n=32) of our patients developed bacteremia. Bacteremia was associated with a surgical duration of ≥80min. Patients with bacteremia incurred longer hospitalization, and had higher mortality rates. Overall mortality rate of our burns patients has decreased from 4.5% to 2.7% (n=18). Key factors of mortality include inhalational injury, bacteremia and ≥20% TBSA.nnnCONCLUSIONnThis is a large epidemiology study of a tropical region burns centre. A total of 655 burns cases over a 3-year period were analyzed. We analysed the key factors associated with adverse outcomes including burns infection, bacteremia and mortality, factors associated with mortality, and discussed strategies on the optimization of burns care.

Rectus sparing approach to left ventricular assist device exchange and use of the omental flap for coverage

Pinder et al. showed that a significantly lower proportion of facial trauma was making up the plastic surgery caseload in 2007 (6%) compared to that in 1989 (23%). Our results may provide some part of the explanation for this. UK trainees entering junior registrar posts are already less experienced than their counterparts were 20 years ago, and they may now struggle to gain adequate exposure to facial trauma during their progression. Whilst Interface fellowships offer the chance to work with OMFS and ENT, helping build facial trauma experience, such opportunities aim to “fine-tune” senior registrars and assume an already confident grasp of fundamental principles in facial trauma since junior registrar level. Unfortunately if the low rate of referral to plastic surgery continues, then senior registrars may not have acquired the necessary knowledge and skills needed to benefit from such interface fellowships. The British Association of Plastic, Reconstructive and Aesthetic Surgeons Undergraduate Courses have gone some way in demonstrating the positive educational impact of a one-day plastic surgery event and improving knowledge of the speciality. Such courses could be beneficial for GPs and ED and Minor injuries unit staff in providing insight into the scope of plastic surgery with respect to facial trauma. This small study confirms how changes in referral pathways for facial trauma have contributed to a decline in opportunities for plastic surgery trainees in the UK and lends some evidence to previous studies as to why emergency operating in the early years of training has fallen dramatically. Ideally a higher response rate would be needed to confirm this, however from the 70% of EDs who responded it is evident that the majority refer to specialities other than plastics when dealing with facial trauma. Plastic surgeons have much to offer in the area of facial trauma, and continuing with such low numbers of referrals may have detrimental effects on future UK trainees in plastics. We recommend increasing referrals for facial trauma, which could be done by agreeing cover protocols with allied specialities and improving insight into the scope of facial plastic surgery within primary care and EDs. The alternative option is to accept that facial (in particular bony) trauma has fallen into the remit of allied specialities and to remove it from the plastic surgery syllabus in the UK. However the authors feel that efforts should be made wherever possible to retain facial trauma in plastics as it provides fundamental learning and experience relevant to both reconstructive and aesthetic head and neck surgery.

Two-Stage Latissimus Dorsi Flap with Implant for Unilateral Breast Reconstruction: Getting the Size Right.

Background The aim of unilateral breast reconstruction after mastectomy is to craft a natural-looking breast with symmetry. The latissimus dorsi (LD) flap with implant is an established technique for this purpose. However, it is challenging to obtain adequate volume and satisfactory aesthetic results using a one-stage operation when considering factors such as muscle atrophy, wound dehiscence and excessive scarring. The two-stage reconstruction addresses these difficulties by using a tissue expander to gradually enlarge the skin pocket which eventually holds an appropriately sized implant. Methods We analyzed nine patients who underwent unilateral two-stage LD reconstruction. In the first stage, an expander was placed along with the LD flap to reconstruct the mastectomy defect, followed by gradual tissue expansion to achieve overexpansion of the skin pocket. The final implant volume was determined by measuring the residual expander volume after aspirating the excess saline. Finally, the expander was replaced with the chosen implant. Results The average volume of tissue expansion was 460 mL. The resultant expansion allowed an implant ranging in volume from 255 to 420 mL to be placed alongside the LD muscle. Seven patients scored less than six on the relative breast retraction assessment formula for breast symmetry, indicating excellent breast symmetry. The remaining two patients scored between six and eight, indicating good symmetry. Conclusions This approach allows the size of the eventual implant to be estimated after the skin pocket has healed completely and the LD muscle has undergone natural atrophy. Optimal reconstruction results were achieved using this approach.