Improved sensory recovery with a novel dual neurorrhaphy technique for breast reconstruction with free muscle sparing TRAM flap technique.

BACKGROUND: We describe a new dual neurorrhaphy method for a free abdominal-based flap and compare sensory recovery with this novel technique to that with conventional neurorrhaphy technique for breast reconstruction. METHODS: 70 breast cancer patients underwent muscle sparing innervated transversal rectus abdominis myocutaneous flap (neuro ms-TRAM) breast reconstruction with either a novel dual neurorrhaphy technique (N = 41) or single (N = 29) neurorrhaphy only. Dual neurorrhaphy was performed on both sides and single neurorrhaphy on one side of the flap, using the end-to-end or end-to-side technique. Two years postoperatively, quantitative sensory testing (QST) was performed for tactile, and thermal sensory modalities, and other tests included sharp-blunt, vibration, and two-point discrimination. Sensory modalities were scored either zero (abnormal) or one point (normal) at each test site against normal reference values (five sites for most tests). The total sensory scores (TSC) were calculated on the basis of the sums of the individual test scores, and all data are presented as the median (interquartile range, IQR). RESULTS: The median of TSC in the breast reconstruction with the dual neurorrhaphy was higher (15.3, IQR 11.8-19.4), than that with the single neurorrhaphy (11.5, IQR 9.1-17.4) (P = 0.037). Regarding the different sensory modalities, the dual technique especially enhanced the tactile (P = 0.005) and cool detection (P = 0.021) recovery compared to the single neurorrhaphy. CONCLUSIONS: Dual neurorrhaphy improved the sensory recovery of the reconstructed breast, and may therefore be recommended for clinical practice. © 2014 Wiley Periodicals, Inc. Microsurgery 37:21-28, 2017.

Neuropilin-2 and vascular endothelial growth factor receptor-3 are up-regulated in human vascular malformations.

Despite multiple previous studies in the field of vascular anomalies, the mechanism(s) leading to their development, progression and maintenance has remained unclear. In this study, we have characterized the expression levels of vascular endothelial growth factors and their receptors in 33 human vascular anomalies. Analysis with quantitative real-time PCR and gene-specific assays showed higher expression of neuropilin-2 (NRP2) and VEGF-receptor-3 (VEGFR-3) mRNAs in vascular malformations (VascM) as compared to infantile hemangiomas (Hem). In addition, the expression levels of PlGF and VEGF-C mRNA were significantly higher in venous VascM when compared to the other VascM and Hem. Higher expression of NRP2 and VEGFR-3 were confirmed by immunohistochemistry. To further study the importance of NRP2 and VEGFR-3, endothelial cell (EC) cultures were established from vascular anomalies. It was found that NRP2 and VEGFR-3 mRNA levels were significantly higher in some of the VascM ECs as compared to human umbilical vein ECs which were used as control cells in the study. Furthermore, adenoviral delivery of soluble decoy NRP2 prevented the proliferation of ECs isolated from most of the vascular anomalies. Our findings suggest that NRP2 functions as a factor maintaining the pathological vascular network in these anomalies. Thus, NRP2 could become a potential therapeutic target for the diagnosis and treatment of vascular anomalies.

A microneurovascular TRAM flap does not compromise abdominal sensibility more than a conventional one.

BACKGROUND: Classic abdominoplasty for a transverse rectus abdominis musculocutaneous (TRAM) flap breast reconstruction impairs abdominal somatosensory function at the donor site. The aim of this study was to investigate whether the type of surgical procedure has an effect on somatosensory alterations of abdominal skin after TRAM flap breast reconstruction. METHODS: Sixty patients (mean ± SD age, 50 ± 6.0 years) who underwent microvascular TRAM flap breast reconstruction and 20 healthy subjects (control group; mean age, 46 ± 6.7 years) participated in the study. Twenty patients had bilateral-nerve anastomosis, 20 had single-nerve anastomosis, and 20 underwent no nerve dissection for the TRAM flap. Clinical sensory examination and tactile and thermal quantitative sensory testing were performed and a patient questionnaire was administered at a mean of 2 to 4.5 years after surgery. RESULTS: All surgical techniques produced significant sensory impairment below the umbilicus, but there were no significant differences in total sensibility scores between the groups with single-nerve (mean sensibility score, 21.98 ± 2.7) and double-nerve (mean sensibility score, 20.71 ± 3.6) anastomosis of the TRAM flap. The best sensibility scores were found in the group with single-nerve dissection. Fifteen percent of patients complained of mild pain, and 13 percent felt occasional tactile hyperesthesia in their abdominal skin, mostly around the umbilicus and scars. CONCLUSIONS: In this study, unilateral or bilateral nerve dissection when preparing and lifting a TRAM flap did not seem to increase sensory alterations or postoperative pain in the abdominal donor site after breast reconstruction surgery. Cautious microneurovascular dissection techniques may even improve sensory recovery of the abdominal skin after TRAM flap breast reconstruction surgery.

A new approach to microneurovascular TRAM-flap breast reconstruction--a pilot study.

BACKGROUND: The aims of the present study were to investigate whether microneurovascular breast reconstruction with a free transverse rectus abdominis musculocutaneous (TRAM) flap and nerve repair with nerves other than ThIV and ThXI improve sensory recovery of the breast compared to traditional free TRAM flap without nerve repair, and which nerve is optimal for the neural anastomosis of the flap. METHODS: Twenty breast cancer patients underwent breast reconstruction with a free TRAM flap and nerve repair (neuro-TRAM) with the best available nerve from the axillary area and 20 control patients had traditional free TRAM flap without nerve repair (standard-TRAM). Neurorrhaphy was done by end-to-end or end-to-side techniques. Sensory and quantitative sensory testings (QST) were performed. Patient satisfaction was evaluated by a clinical questionnaire. The results were analysed by Mann-Whitney tests. RESULTS: Mean follow-up was 32 months for the neuro-TRAM, and 54 months for the standard-TRAM group. Sensory outcome was better in the neuro-TRAM group (sensory score 45% of that of the contralateral breast) than in the standard-TRAM group (26% of the contralateral side). The median (quartiles) of total scores in the operated breasts was 12.9 (9.5-19.2) in neuro-TRAM group and 8.1 (3.5-10.7) in standard-TRAM group (Mann-Whitney Test (p=0.006)). All nerves available in the thoracic and axillary areas and both of the anastomosis techniques were successful in the reinnervation procedure. Nerve repair did not influence overall patient satisfaction. CONCLUSIONS: This study indicates that any nerve repair results in improved sensory recovery after TRAM flap breast reconstruction. Any nerve available for anastomosis in the recipient site is potentially able to provide moderately good cutaneous sensibility to the TRAM-breast.

Comparison of premortem clinical diagnosis and autopsy findings in patients with burns.

INTRODUCTION: Despite the diagnostic advancements, some clinically important diagnoses remain undetected during intensive care in burn patients. The aim of this study was to compare the premortem clinical diagnoses and autopsy findings. PATIENTS AND METHODS: A retrospective review of all burn deaths during 1995-2005 was conducted. The clinical diagnoses and autopsy reports were reviewed, and diagnostic discrepancies were classified into four categories, according to the impact on the treatment. RESULTS: Overall mortality during the study period was 5.4%. Altogether 74 deaths were recorded, of which 71 were included in the study. Typical patient was a 58-year-old male with flame burn of %TBSA 49, ABSI 10. Clinical diagnostic discrepancies were found in 14.1% of the patients; one diagnostic discrepancy was recorded in each of the patients. Of these diagnostic discrepancies, 8.5% were considered major, and 5.6% would have altered the clinical outcome or therapy, if known at the time. Diagnostic discrepancies consisted of one cardiovascular, seven respiratory and two gastrointestinal missed diagnosis. The most common missed diagnosis was pneumonia. CONCLUSION: This study emphasizes the usefulness of autopsies to provide valuable clinical data for the treatment of burn patients. It also highlights the few missed diagnoses which may occur in burn patients.

Vascular endothelial growth factor C-induced collateral formation in a model of myocardial ischemia.

BACKGROUND: Besides being a known lymphangiogenic activator, vascular endothelial growth factor (VEGF)-C may express angiogenic potential by proteolytic cleavage and activation of endothelial cells. We assessed myocardial collateral formation and functional changes after adenovirus-mediated VEGF-C gene transfer in an ischemic porcine model. METHODS: Fifteen Landrace piglets underwent Ameroid-induced gradual occlusion of the left circumflex artery (LCx) and consequent progressive myocardial ischemia. Three weeks after Ameroid placement, the animals underwent gated 99mTc SPECT during rest and stress, in vivo angiography and 18FDG PET. Pigs were randomized to intramyocardial injections of adenoviruses encoding vascular endothelial growth factor (VEGF-C; n = 7) or control beta-galactosidase (LacZ; n = 5). Four weeks later, the examinations were repeated and histology was analyzed. RESULTS: Angiography showed significant progression of LCx stenosis in both groups during the treatment period. Left ventricular wall thickening (LVWT) at the LCx area in gated 99mTc SPECT remained unchanged in the VEGF-C group, indicating that VEGF-C prevented progression of myocardial ischemia, whereas LVWT deteriorated in the LacZ group (p = 0.042). Semi-quantitative assessment of 18FDG PET suggests more reduction in ischemia in the adVEGF-C group than in controls (p = 0.052). Angiography showed significant clustering of collaterals in the adVEGF-C gene transfer area compared that in LacZ (p = 0.004). von Willebrand factor staining revealed a significantly (p = 0.03) greater number of microvessels in the adVEGF-C-treated myocardium. CONCLUSIONS: This appears to be the first large-animal study in which, during progressive ischemia, functional and metabolic benefits of intramyocardial VEGF-C gene transfer were apparent. VEGF-C-induced collateral formation occurred at the site of gene transfer. The angiogenic potency of VEGF-C deserves further study as a therapeutic option.

Vascular endothelial growth factors C and D and their VEGFR-2 and 3 receptors in blood and lymphatic vessels in healthy and arthritic synovium.

OBJECTIVE: To localize vascular endothelial growth factor C (VEGF-C) and VEGF-D in synovial specimens in relation to their VEGFR-2 and VEGFR-3 receptors in blood and lymphatic vessels. METHODS: Immunohistochemical staining and messenger RNA analysis from control and arthritic synovial membrane specimens. RESULTS: Quantitative RT-PCR disclosed that VEGF-C mRNA copy numbers were higher than VEGF-D mRNA copy numbers in the rheumatoid arthritis (RA), osteoarthritis, and control patient groups studied (p < 0.01). Immunohistochemical staining localized VEGF-C to synovial lining cell layer, pericytes, and smooth muscle cells of blood vessels. The number of VEGF-C positive cells was increased in the synovial lining of ankylosing spondylitis (AS) and RA compared to control synovium. However, in contrast to control synovial lining, little if any VEGF-D was detected in AS or RA synovial lining. VEGFR-2 expressing stromal blood vessels, also positive for the vascular endothelial marker PAL-E and the basement membrane marker laminin, were more abundant in RA and AS than in controls. Interestingly, the lymphatic endothelial receptor VEGFR-3 was also expressed in most synovial vessels, especially in the sublining capillaries and venules. CONCLUSION: VEGF-C is strongly expressed in the hypertrophic synovial lining of arthritic joints, whereas VEGF-D expression is very low in AS and RA. The expression of VEGF-C and VEGF-D in pericytes and smooth muscle cells suggests that these factors may have a role in maintaining vascular homeostasis. The VEGF receptors VEGFR-2 and VEGFR-3 are present in most of the sublining blood vessels. The expression of the lymphatic marker VEGFR-3 in the sublining blood vessels may relate to fluid filtration and/or fenestrations. The relatively few lymphatic vessels along with increased vascular permeability in RA may contribute to the development of tissue edema and joint stiffness.