Risk Factors for Developing Nonmelanoma Skin Cancer after Lung Transplantation.

BACKGROUND: Nonmelanoma skin cancer (NSMC) is the most common malignancy after organ transplantation. Lung transplant recipients (LTRs) are particularly prone to develop NMSC as compared to renal or hepatic transplant recipients due to higher dosages of immunosuppression needed. Everolimus, an immunosuppressant used in organ transplant recipients, is thought to inherit a lower risk for NMSC than calcineurin inhibitors, especially in renal transplant recipients. It is currently unknown whether this also applies to LTRs. OBJECTIVES: To determine risk factors for NMSC and precancerous lesions after lung transplantation (LTx) and to characterize the effect of everolimus-based regimens regarding this risk. MATERIALS AND METHODS: 90 LTRs and former participants of the interventional trial "Immunosuppressive Therapy with Everolimus after Lung Transplantation", who were randomized to receive either an everolimus- or mycophenolate mofetil- (MMF-) based regimen, were enrolled and screened in this retrospective, single-center cohort study. RESULTS: After a median follow-up of 101 months, we observed a prevalence of 38% for NMSC or precancerous lesions. 33% of the patients continuously receiving everolimus from LTx to dermatologic examination compared to 39% of all other patients, predominantly receiving an MMF-based regimen, were diagnosed with at least one NMSC or precancerous lesion (P=.66). Independent risk factors for NMSC or precancerous lesions after LTx were male sex and duration of voriconazole therapy. CONCLUSION: NMSC or precancerous lesions were very common after LTx, and risk factors were similar to previous reports on LTRs. Everolimus did not decrease this risk under the given circumstances of this study. Patients should be counseled regarding their risk, perform vigorous sunscreen, and undergo regular dermatological controls, regardless of their immunosuppressive regimen.

Vessel transformation in chronic wounds under topical negative pressure therapy: an immunohistochemical analysis.

The underlying physiological mechanism of topical negative pressure (TNP) therapy is not yet completely understood. This prospective clinical study aims to clarify a potential influence of TNP therapy on vessel proliferation and hypoxia in chronic wounds. TNP was applied on chronic wounds of 16 patients (-125 mmHg) to prepare them for a plastic-surgical reconstruction using free or pedicled flaps. Tissue biopsies were taken from the wound edge and wound bed at different time points. All samples were stained with haematoxylin and eosin, hypoxia-induced factor-1α and endothelial cell markers (CD31 and CD34) for the immunohistological analysis of inflammation, hypoxia and vessel proliferation. Between day 5 and day 8 of treatment, a considerable increase in blood vessel density could be observed, reaching a maximum of approximately 200% in contrast to the vessel density prior to treatment. In addition, the number of hypoxic and inflammatory cells was found to be increased at particular time points. This study demonstrates a stimulating effect on vessel proliferation under TNP treatment. TNP appears to support (neo-) angiogenesis and transformation of chronic non-healing wounds in a physiological wound healing process when combined with surgical debridement. This effect underlines the positive influence of TNP in the treatment of chronic wounds as shown by various clinical reports.

Changes of anabolic processes at the cellular and molecular level in chronic wounds under topical negative pressure can be revealed by transcriptome analysis.

Chronic wounds--as defined by the World Union of Wound Healing Societies (WUWHS)--are a considerable worldwide health care expense and impair quality of life. In order for chronic wounds to heal, these wounds must be transformed to a more acute state to begin the healing process. Topical negative pressure (TNP) with reticulated open cell foam (ROCF) is known to promote healing in certain types of chronic wounds. However, little is known about changes at the cellular or molecular level in wounds under various treatments, especially under the physical forces induced to tissue by TNP. In the current study, chronic wound samples were obtained during routine wound debridements prior to treatment and 7-12 days after initiating TNP with a continuous setting at -125 mmHg. Whole genome transcriptome microarray analyses were performed on samples to better understand how TNP with ROCF affects these types of wounds. It was found that more genes were expressed following TNP with ROCF as compared to before therapy and to normal, non-wounded tissue. In this study, we show that TNP with ROCF transforms the chronic wound from its inflammation (non-healing) state into more of a progressive, healing phenotype from a molecular point of view with expression of genes that are commonly associated with these terms.

Gene expression analysis of ischaemia and reperfusion in human microsurgical free muscle tissue transfer.

The aim of this study was to analyse various gene expression profiles of muscle tissue during normoxia, ischaemia and after reperfusion in human muscle free flaps, to gain an understanding of the occurring regulatory, inflammatory and apoptotic processes on a cellular and molecular basis. Eleven Caucasian patients with soft tissue defects needing coverage with microsurgical free muscle flaps were included in this study. In all patients, the muscle samples were taken from free myocutaneous flaps. The first sample was taken before induction of ischaemia in normoxia (I), another one after ischaemia (II), and the last one was taken after reperfusion (III). The samples were analysed using DNA-microarray, real-time-quantitative-PCR and immunohistochemistry. DNA-microarray analysis detected multiple, differentially regulated genes when comparing the different groups (I-III) with statistical significance. Comparing ischaemia (II) versus normoxia (I) educed 13 genes and comparing reperfusion (III) versus ischaemia (II) educed 19 genes. The comparison of reperfusion (III) versus normoxia (I) yielded 100 differentially regulated genes. Real-time-quantitative-PCR confirmed the results of the DNA-microarrays for a subset of four genes (CASP8, IL8, PLAUR and S100A8). This study shows that ischaemia and reperfusion induces alterations on the gene expression level in human muscle free flaps. Data may suggest that the four genes CASP8, IL8, PLAUR and S100A8 are of great importance in this context. We could not confirm the DNA-microarry and real-time-quantitative-PCR results on the protein level. Finally, these findings correspond with the surgeon's clinical experience that the accepted times of ischaemia, generally up to 90 min., are not sufficient to induce pathophysiological processes, which can ultimately lead to flap loss. When inflammatory and apoptotic proteins are expressed at high levels, flap damage might occur and flap loss is likely. The sole expression on mRNA level might explain why flap loss is unlikely.

Scars and perforator-based flaps in the abdominal region: a contraindication?

BACKGROUND: Although multiple strategies for autologous breast reconstruction exist, a vertical midline scar in the abdominal wall as a result of previous laparatomy or abdominoplasty represents a major surgical challenge. To date, little research has been conducted on the regeneration potential of the abdominal wall's superficial vascular, perforator and choke vessel system after surgery using a vertical approache. METHODS: We present the cases of 8 patients, of whom 7 underwent autologous breast reconstruction. One patient received a thigh reconstruction. All patients had a vertical abdominal midline scar as a result of a previous surgical intervention. In 3 of the 7 patients, the breast was reconstructed using an MS-2-vertical rectus abdominis myocutaneous (VRAM) free flap. In 4 of these patients, an MS-2-transverse rectus abdominis myocutaneous (TRAM) free flap was performed. The thigh reconstruction used a transverse deep inferior epigastric perforator (DIEP) free flap. Clinical followup was done 12 months after operation. RESULTS: All 3 patients who received an MS-2-VRAM had good aesthetic results. Vertical midline scars had no negative effect on surgical outcomes, perfusion and tissue viability of the 4 MS-2-TRAM and transverse DIEP free flaps. CONCLUSION: These clinical findings indicate that the regeneration potential of the abdominal wall's superficial vascular system in the presence of vertical surgical scars has been greatly underestimated. Use of MS-2-VRAM free flaps in patients with vertical abdominal scars seems to be a suitable and successful alternative in the reconstruction algorithm.

Aesthetic correction of tuberous breast deformity: lessons learned with a single-stage procedure.

Tuberous breast deformity is a pathologic condition of the breast affecting teenage women. The aberration of breast shape in tuberous breast deformity consisting of a constricting ring at the breast base, breast tissue deficiency, and herniation of breast tissue into the nipple-areola-complex with areola enlargement and additional asymmetry makes the surgical correction challenging. In the present study, 15 patients were operated using a surgical procedure, which addresses all aspects of the deformity at a one-stage operation. The described technique results in a periareolar scar only, and the use of tissue expanders or skin flaps is unnecessary. Minor periareolar scar revision surgery was necessary in eight of 15 patients (53%) because of hypertrophic or expanded scarring. In two patients, implant dislocation occurred and therefore surgical revision was necessary. In all cases, an excellent final aesthetic result with a high patient satisfaction was achieved.

Acute and diffuse postoperative bleeding after free latissimus dorsi flap--Factor XIII deficiency: a case report and review of the literature.

BACKGROUND: Factor XIII deficiency is a rare inherited bleeding disorder that is often difficult to diagnose. As there are no standard screening tests established patients with Factor XIII deficiency are not correctly identified. Especially postoperative bleeding and haemorrhage after difficult plastic reconstructive operations such as free flap transfer may lead the plastic surgeon to the wrong diagnosis. This again leads to the wrong indication such as revision with the aim to find a surgical origin of bleeding. Instead a haematological deficiency such as Factor XIII is the reason for acute postoperative bleeding and haemorrhage. CASE REPORT: We report the case of a 69-year old Caucasian male who received a free latissimus dorsi flap to the right knee after osteomyelitis and infection of a knee total endoprothesis. The patient had severe postoperative bleeding and haemorrhage from all 8 drains including the donor side of the split thickness skin graft area. Shortly before the indication of performing a revision and trying to find the surgical origin of bleeding a factor XIII test was performed. The results showed a high deficiency of factor XIII which was immediately replaced by 2500 Units (i.E.) Fibrogammin. Within 12 hours the bleeding rapidly reduced and no revision was necessary. CONCLUSIONS: Postoperative acute but diffuse bleeding after free flap operations in plastic surgery may not be all due to insufficient operative techniques.

Coverage of exposed bones and joints in critically ill patients: lower extremity salvage with topical negative pressure therapy.

BACKGROUND: Soft tissue defects of the limb with exposure of tendons and bones in critically ill patients usually lead to extremity amputation. A potential treatment with topical negative pressure may allow split-thickness skin grafting to the bone, which leads to limb salvage. MATERIALS AND METHODS: We report on 21 multimorbid patients, 46 to 80 years of age, with severe lower limb soft tissue loss and infection with exposed bone following débridement with critical limb ischemia. Attempts to salvage the extremities were undertaken with repeated surgical débridement followed by vacuum-assisted closure therapy and subsequent split-thickness skin grafting procedures. RESULTS: Infection control and limb salvage were achieved in all cases with multiple débridements, topical negative pressure therapy, and skin grafts. In all patients, the exposure of tendons and bones was reversible by this strategy without a free flap transfer. DISCUSSION: The patients described in this study were severely compromised by systemic and vascular disorders, so extremity amputation had been considered owing to the overall condition and the exposure of tendons and bones. Since it was possible to salvage the affected limbs with this straightforward and simple procedure, this type of treatment should be considered as a last attempt to prevent amputation.

Insulin attenuates apoptosis and exerts anti-inflammatory effects in endotoxemic human macrophages.

BACKGROUND: Insulin decreases the incidence of sepsis and improves mortality of critically ill patients. In endotoxemic as well as in thermally injured rats, insulin attenuates the systemic inflammatory response by decreasing the proinflammatory and increasing the antiinflammatory cascade. The aim of the present study was to determine the effects of insulin on cell survival, cell activity, apoptosis, and proinflammatory response in a human macrophage-like cell line (THP-1 cells) stressed with lipopolysaccharide (LPS). MATERIALS AND METHODS: Human macrophages were stressed with LPS and received either saline or insulin. Cell viability was analyzed by MTS, apoptosis was detected using JC-1 and terminal deoxynucleotidyl transferase-mediated nick end labeling-staining, and to elucidate on the signaling pathway, we used wortmannin as a phosphatidylinositol-3-kinase inhibitor. Tumor necrosis factor (TNF) and interleukin-1beta (IL-1beta) were measured to determine the effect of insulin on proinflammatory cytokine expression. RESULTS: Insulin caused a significant increase in cell viability and significantly reduced apoptosis in LPS-stimulated human macrophages in a dose-dependent manner. The antiapoptotic effect of insulin could be completely blocked with the addition of wortmannin. Insulin significantly decreased TNF and IL-1beta in endotoxemic human macrophages. CONCLUSIONS: Our results indicate that insulin exerts antiapoptotic effects and reduces the expression of proinflammatory cytokines in endotoxemic human macrophages. The antiapoptotic effects are mediated via the phospatidylinositol-3-kinase-pathway.

The versatility of the distally based peroneus brevis muscle flap in reconstructive surgery of the foot and lower leg.

Soft tissue and bone defects of the lower leg, ankle, and heel region often require coverage by local or distant flaps. The authors successfully used the distally based peroneus brevis muscle flap for the treatment of 15 patients with osteomyelitis (n = 5), melanoma (n = 1), Achilles tendon defects (n = 6), posttraumatic bone defects (n = 2), and chronic diabetic heel ulcer (n = 1). The size of the defects ranged from 6 to 60 cm. All defects were covered successfully without major complications by the muscle flap. The distally based peroneus brevis muscle represents a very reliable flap for coverage of small and moderate defects of the medial and lateral malleolus, the Achilles tendon, and the heel area. This flap offers a convincing alternative for covering defects in the distal leg region and is often preferable to the use of free flaps because the surgery is rapidly performed and does not require microsurgical expertise.