Christian D. Taeger

Results of combined vascular reconstruction and free flap transfer for limb salvage in patients with critical limb ischemia

OBJECTIVE Combined vascular reconstruction and free flap transfer has been established in centers as a feasible therapeutic option in cases with critical limb ischemia (CLI) and large tissue defects otherwise destined for major amputation. However, the number of patients treated with this combined approach is limited, and data regarding long-term follow-up and functional outcome are scarce. We therefore report our 10-year experience in free flap transplantation after vascular reconstruction as a last attempt for limb salvage, with special emphasis of complication rate, limb salvage, and postoperative mobility. METHODS CLI patients undergoing combined vascular reconstruction and consequent free flap transfer from 2003 to 2013 were retrospectively observed. Of 80 cases in total, patients with traumatic and oncologic indications were excluded; 33 (mean age, 66 years; range, 51-82 years) of these cases were performed for limb salvage and were included in this study. Long-term follow-up was possible in 32 of 33 patients (mean, 58 months; range, 2-126 months). RESULTS Thirty-three patients were analyzed. We performed arterial revascularization with 9 arteriovenous loops, 23 bypass grafts (10 popliteal-pedal, 9 femoral-crural, and 4 femoral-popliteal), and 1 venous interposition graft. For defect coverage, tissue transfer was comprised of six different flap entities (10 latissimus dorsi, 2 gracilis, 1 anterior lateral thigh, 7 rectus abdominis, 11 radialis, and 2 greater omentum flaps). Complications occurred in 16 of 33 patients (49%). Early complications included eight acute occlusions of arterial reconstructions; major bleedings were seen in eight patients as well. There were two flap losses and one major amputation in the early postoperative period. No in-hospital deaths were observed. Late results revealed a limb salvage rate of 87% after 1 year and 83% after 5 years. Amputation-free survival was 87% after 1 year and 75% after 5 years. Overall survival was 100% and 87% after 1 year and 5 years, respectively. Follow-up showed 42% of patients with no limitations in ambulation, 54% with maintained preoperative ambulatory status, and one bedridden patient. CONCLUSIONS The combined approach for limb salvage in CLI patients is associated with excellent results in limb salvage and functional outcome in patients who would otherwise be candidates for major amputation, despite an initially elevated complication rate. The option of combined revascularization with free tissue transfer should be evaluated in all mobile patients with CLI, large tissue defects, and exposed tendon or bone structures before major amputation. However, further studies are required to support these results.

Cracking the perfusion code?: Laser-assisted Indocyanine Green angiography and combined laser Doppler spectrophotometry for intraoperative evaluation of tissue perfusion in autologous breast reconstruction with DIEP or ms-TRAM flaps

The aim of this prospective study was to assess the correlation of flap perfusion analysis based on laser-assisted Indocyanine Green (ICG) angiography with combined laser Doppler spectrophotometry in autologous breast reconstruction using free DIEP/ms-TRAM flaps. Between February 2014 and July 2015, 35 free DIEP/ms-TRAM flaps were included in this study. Besides the clinical evaluation of flaps, intraoperative perfusion dynamics were assessed by means of laser-assisted ICG angiography and post-capillary oxygen saturation and relative haemoglobin content (rHb) using combined laser Doppler spectrophotometry. Correlation of the aforementioned parameters was analysed, as well as the impact on flap design and postoperative complications. Flap survival rate was 100%. There were no partial flap losses. In three cases, flap design was based on the angiography, contrary to clinical evaluation and spectrophotometry. The final decision on the inclusion of flap areas was based on the angiographic perfusion pattern. Angiography and spectrophotometry showed a correlation in most of the cases regarding tissue perfusion, post-capillary oxygen saturation and relative haemoglobin content. Laser-assisted ICG angiography is a useful tool for intraoperative evaluation of flap perfusion in autologous breast reconstruction with DIEP/ms-TRAM flaps, especially in decision making in cases where flap perfusion is not clearly assessable by clinical signs and exact determination of well-perfused flap margins is difficult to obtain. It provides an objective real-time analysis of flap perfusion, with high sensitivity for the detection of poorly perfused flap areas. Concerning the topographical mapping of well-perfused flap areas, laser-assisted angiography is superior to combined laser Doppler spectrophotometry.

Is there a Rationale for Autologous Breast Reconstruction in Older Patients? A Retrospective Single Center Analysis of Quality of life, Complications and Comorbidities after DIEP or ms‐TRAM Flap Using the BREAST‐Q

Autologous breast reconstruction with the deep inferior epigastric perforator (DIEP) or muscle‐sparing transverse rectus abdominis myocutaneous (ms‐TRAM) flap is a common method in the majority of patients after mastectomy. Because of an increased perioperative risk profile the benefit in older patients is questionable. To assess the postoperative quality of life and peri‐ and post‐operative complications of older compared to younger patients is the aim of this retrospective study. In a retrospective analysis 39 older (i.e. >60 years) and 140 younger patients (i.e. <60 years) with autologous breast reconstruction in the Department of Plastic Surgery at the University Hospital of Erlangen‐Nuernberg were surveyed at least 6 month postoperative using the BREAST‐Q questionnaire. Correlations were generated between comorbidities and complications. Significant differences were observed regarding hospitalization, pre‐existing diseases and the choice of DIEP versus ms‐TRAM flaps. Parameters such as major and minor complications, bulging or hernia and risk factors (e.g. smoking or obesity) showed no significant differences. The results of the questionnaire parameters showed no significant difference between both groups, revealing high satisfaction with the aesthetic result and an improvement in quality of life independent of age. Autologous breast reconstruction after mastectomy generates a gain in quality of life and shows a good to excellent overall satisfaction in older as well as younger patients. Despite a longer hospitalization and a different risk profile there were no significant differences regarding minor and major complications in the postoperative course. Hence autologous breast reconstruction for older patients is justified and should be taken into consideration.

Immunohistochemical evaluation after ex vivo perfusion of rectus abdominis muscle flaps in a porcine model.

Background: The purpose of this study was to investigate whether and how the extracorporal perfusion of muscle flaps with a miniaturized perfusion system could change the expression of the proapoptotic protein caspase 3 and of the ischemia-sensitive protein hypoxia-inducible factor (HIF)-1&agr; as a first step toward the development of a clinically reliable tool for circumventing ischemia problems in free muscle flap transfer. Methods: In this study, 25 porcine rectus abdominis muscles were used and assigned to five different groups. In the baseline group (group I), the muscle flap remained in situ; in groups II and III, the muscle flap was harvested and remained ex vivo without or with subsequent single-shot heparinized flush; and in groups IV and V, the flaps were perfused with either heparinized autologous whole blood or crystalloid fluid (Jonosteril), using a miniaturized perfusion system without Exogen oxygenation. Muscle samples were taken for immunohistochemical evaluation. The proportion of positive cells for HIF-1&agr; and caspase 3 was compared for each group (groups II through V) to the baseline group (group I). Results: The expression of HIF-1&agr; and caspase 3 was increased in both groups without perfusion and was low during in vivo perfusion and extracorporal perfusion with crystalloid fluid. Heparinized autologous whole blood perfusion shows no protective effect, in contrast to the crystalloid fluid. Conclusions: The data of this study indicate that the extracorporal perfusion of muscle flaps with crystalloid fluid is a possible protective strategy against ischemia. Autologous heparinized whole blood seems to have no additional protective effect in a pure perfusion setting without oxygenation.

Online oxygen measurements in ex vivo perfused muscle tissue in a porcine model using dynamic quenching methods

IntroductionTransplantation of autologous free tissue flaps is the best applicable technique for treating large and complex tissue defects and still has one major failure criterion. Tissue—and in particular muscle tissue—is strongly sensitive to ischemia, thus after a critical period of oxygen depletion the risk of a partial or total flap loss is high.Materials and methodsFor that reason a miniaturized ex vivo perfusion system has been developed, that supplies the tissue during operational delays. The purpose of this study was to determine the oxygenation levels during such a perfusion using different perfusates and therefore to objectify if a complementary oxygenation unit is required to improve perfusion quality. The oxygen levels of the tissue, as well of the perfusate, were measured by using minimal invasive optical oxygen sensors that are based on dynamic quenching. The ex vivo perfused tissue was the porcine rectus abdominis muscle.ResultsResults show, that during perfusion with heparinized crystalloid fluid (Jonosteril®) and heparinized autologous whole blood, additional oxygenation of the perfusion reactor led to different ex vivo oxygen tissue saturations, which can be detected by dynamic quenching.ConclusionDynamic quenching methods are a promising and valuable technique to perform online oxygen measurements in ex vivo perfused muscle tissue in a porcine model.

Emergency arterio-venous loop for free-flap defect reconstruction of the lower thigh with a post-irradiated and heavily infected wound.

Although being a safe and standardised procedure, free‐flap reconstruction can be harmful if unpredictable situations occur intraoperatively. The case presented reveals a situation in which an unscheduled interdisciplinary approach allowed to complete our reconstructive aim. An extensive defect at the thigh was planned for reconstruction by means of a free rectus abdominis flap. As the distant part of the flap showed a compromised perfusion during operation and had to be partially discarded, our colleagues from the vascular surgery department created an arterio‐venous loop for anastomosis. This allowed a more distant positioning of the flap and ensured a complete defect reconstruction.

Ischaemia-related cell damage in extracorporeal preserved tissue - new findings with a novel perfusion model.

Tissue undergoing free transfer in transplant or reconstructive surgery always is at high risk of ischaemia‐related cell damage. This study aims at assessing different procedures using an extracorporeal perfusion and oxygenation system to investigate the expression of hypoxia inducible factor (HIF)‐1‐α as marker for hypoxia and of the pro‐apoptotic protein Caspase‐3 in skeletal muscle to elucidate potential improvements in tissue conservation. Twenty‐four porcine rectus abdominis muscles were assigned to five different groups and examined after they had been extracorporeally preserved for 60 min. time. Group I was left untreated (control), group II was perfused with a cardioplegic solution, group III was flushed with 10 ml of a cardioplegic solution and then left untreated. Group IV and V were perfused and oxygenated with either an isotone crystalloid solution or a cardioplegic solution. Among others, immunohistochemistry (Caspase‐3 and HIF‐1‐α) of muscle samples was performed. Furthermore, oxygen partial pressure in the perfusate at the arterial and venous branch was measured. Expression of Caspase‐3 after 60 min. was reduced in all groups compared to the control group. Furthermore, all groups (except group III) expressed less HIF‐1‐α than the control group. Oxygenation leads to higher oxygen levels at the venous branch compared to groups without oxygenation. Using an extracorporeal perfusion and oxygenation system cell damage could be reduced as indicated by stabilized expressions of Caspase‐3 and HIF‐1‐α for 60 min. of tissue preservation. Complete depletion of oxygen at the venous branch can be prevented by oxygenation of the perfusate with ambient air.

Assessing viability of extracorporeal preserved muscle transplants using external field stimulation: a novel tool to improve methods prolonging bridge-to-transplantation time

Preventing ischemia-related cell damage is a priority when preserving tissue for transplantation. Perfusion protocols have been established for a variety of applications and proven to be superior to procedures used in clinical routine. Extracorporeal perfusion of muscle tissue though cumbersome is highly desirable since it is highly susceptible to ischemia-related damage. To show the efficacy of different perfusion protocols external field stimulation can be used to immediately visualize improvement or deterioration of the tissue during active and running perfusion protocols. This method has been used to show the superiority of extracorporeal perfusion using porcine rectus abdominis muscles perfused with heparinized saline solution. Perfused muscles showed statistically significant higher ability to exert force compared to nonperfused ones. These findings can be confirmed using Annexin V as marker for cell damage, perfusion of muscle tissue limits damage significantly compared to nonperfused tissue. The combination of extracorporeal perfusion and external field stimulation may improve organ conservation research.

Four-flap compound repair of thoracic hernia after sternum osteomyelitis and omentum flap

DISCUSSION This case illustrates that the interpretation of respiratory functional evaluation must not be considered independently of the patient context. At first, surgery was declined by overlooking the role of a neurologic deficit as the cause of the inability to perform expiratory maneuvers. We could not find other examples of lobectomy performed in quadriplegic patients with such a low preoperative FEV1. No functional data were available in the 3 lobectomies (performed by standard thoracotomy) reported by Rocco and colleagues, but the authors reported that preoperative evaluation may be limited, and the major emphasis must be on clinical expertise and arterial blood gas analysis to approximately determine the surgical risk. In the absence of diffuse pulmonary disease that explains major respiratory insufficiency, low preoperative FEV1 may not necessarily constitute a contraindication to surgery. In addition, vital capacity, which has been proposed as a single global measure of overall ventilatory function status in these cases, was not helpful. To avoid postoperative pulmonary infectious complications related to low expiratory flow rates and incapacity to expectorate, temporary tracheostomy might be a good adjunct to the surgical treatment. In a randomized controlled trial including 102 high-risk patients undergoing lung resection,

Guanylate-binding protein 1 expression from embryonal endothelial progenitor cells reduces blood vessel density and cellular apoptosis in an axially vascularised tissue-engineered construct

BackgroundGuanylate binding protein-1 (GBP-1) is a large GTPase which is actively secreted by endothelial cells. It is a marker and intracellular inhibitor of endothelial cell proliferation, migration, and invasion. We previously demonstrated that stable expression of GBP-1 in murine endothelial progenitor cells (EPC) induces their premature differentiation and decreases their migration capacity in vitro and in vivo. The goal of the present study was to assess the antiangiogenic capacity of EPC expressing GBP-1 (GBP-1-EPC) and their impact on blood vessel formation in an axially vascularized 3-D bioartificial construct in vivo.ResultsFunctional in vitro testing demonstrated a significant increase in VEGF secretion by GBP-1-EPC after induction of cell differentiation. Undifferentiated GBP-1-EPC, however, did not secrete increased levels of VEGF compared to undifferentiated control EPC expressing an empty vector (EV-EPC). In our In vivo experiments, we generated axially vascularized tissue-engineered 3-D constructs. The new vascular network arises from an arterio-venous loop (AVL) embedded in a fibrin matrix inside a separation chamber. Total surface area of the construct as calculated from cross sections was larger after transplantation of GBP-1-EPC compared to control EV-EPC. This indicated reduced formation of fibrovascular tissue and less resorption of fibrin matrix compared to constructs containing EV-EPC. Most notably, the ratio of blood vessel surface area over total construct surface area in construct cross sections was significantly reduced in the presence of GBP-1-EPC. This indicates a significant reduction of blood vessel density and thereby inhibition of blood vessel formation from the AVL constructs caused by GBP-1. In addition, GBP-1 expressed from EPC significantly reduced cell apoptosis compared to GBP-1-negative controls.ConclusionTransgenic EPC expressing the proinflammatory antiangiogenic GTPase GBP-1 can reduce blood vessel density and inhibit apoptosis in a developing bioartificial vascular network and may become a new powerful tool to manipulate angiogenetic processes in tissue engineering and other pathological conditions such as tumour angiogenesis.