The role of the intralesional injection of platelet rich plasma at the morfometric characteristics of the healing of chronic ulcers: an experimental and clinical study

Introduction: Management of chronic ulcers is a challenging problem for the reconstructive surgeon. Various treatment methods, either conservative or surgical, have been used for treating these wounds. Progress in bioengineering provided new techniques and materials, and thus, new therapeutic options. The local application of platelet-rich plasma (PRP) has been reported to accelerate healing of chronic wounds. In the present study, we propose an original technique for applying the PRP, by injecting it in the wound (intralesionally). We used this technique in an experimental model, as well as in a clinical series. The purpose of this prospective study is to evaluate the effectiveness of the intralesional injection of platelet-rich plasma as a local treatment, in the management of non-healing chronic wounds. Experimental Study. Material & Method: We created ulcers, measuring 2X2 cm, at the ears of twenty white New Zealand rabbits. In the ulcers of the right ear, autologous PRP was injected intralesionally, followed by conventional dressings up to 4 weeks. The ulcers of the left ear were treated conservatively. The macroscopic evaluation of the healing process was assessed for a period of 28 days. Results: Nineteen out of twenty ulcers treated with intralesional injection of PRP healed uneventfully within a mean time of 24,9 days. In the group of the conservatively treated ulcers, only seven healed within 28 days. In six cases, an aggravation of the ulcer was recorded, resulting in a full thickness ear defect. Histological evaluation of tissue specimens taken from the wound area, confirmed the acceleration of healing in the PRP-treated ears. Clinical Study. Material & Method: For a period of three years, 28 patients, 16 males and 12 females (mean age 59 years) who presented a non-healing wound in a mean period of 4,6 months, underwent local treatment with intralesional injection of autologous platelet-rich plasma. The etiology of the wound was trauma (n=14), burn (n=2), decubitus ulcer (n=6) and wound dehiscence (n=6). Location of the ulcer involved the lower limb (n=16), the trunk (n=10), the upper extremity (n=1) and the head (n=1). In 19 cases, the wound culture before treatment showed a bacterial load greater than 105/gr of tissue. All wounds had been previously treated conservatively or surgically with unsatisfactory results. Ten patients of our series (group A) had ulcers smaller than 10cm2, classified as stage III according to Shea classification. In eighteen patients (group B), the ulcers were larger or were classified as stage IV. After the preparation of the PRP, surgical debridement was performed and followed by intralesional injection of PRP with an equal distribution within the wound area. Twenty-two patients received a single PRP application and six had multiple applications. Evaluation of the ulcers was done on the 7th and the 14th day after PRP injection, when A histological correlation study was also performed. Results: In 10 patients (group A), the wounds healed with secondary intention within a mean period of seven weeks after PRP treatment. In 16 cases of group B, the PRP application prepared the wound bed and, thus, a lesser surgical procedure was needed, using either skin grafts (n=11) or flaps (n=5). In 2 diabetic patients, no progress of the healing process was recorded. Histological results confirmed the clinical findings concerning the healing acceleration. During the follow-up time (max 26 months) only two recurrences of the healed ulcers occurred, both in diabetic patients. Conclusion: Intralesional injection is a new reliable method of local application of platelet-rich plasma and represents an effective therapeutic option when dealing with non-healing wounds. The advantages of the method, comparing to the traditional application of the PRP on the ulcer, is that PRP injection into the wound allows for continuation of local management and daily changes of dressings, if this required, without the risk of removing the growth factors. Moreover, the method can be immediately associated to a reconstructive procedure for covering the defect, enhancing the healing of the wound and reducing the time needed for complete recovery of the patient. Based on the results of our experimental study, we found significantly higher rates of wound healing in the PRP-treated ulcers. The results of our clinical study show that, in the majority of chronic ulcers, healing acceleration is recorded, leading either to complete epithelisation, or to preparation of the wound bed for the final reconstructive procedure.Εισαγωγή. Σκοπός της παρούσης προοπτικής μελέτης είναι η αξιολόγηση της αποτελεσματικότητας της εφαρμογής συμπυκνώματος αιμοπεταλίων (PRP) στην επιτάχυνση της επούλωσης χρόνιων ελκών, με τη μέθοδο της ενδοτραυματικής ένεσης. Υλικό & Μέθοδος. Πειραματική Μελέτη. Διενεργήθηκε πειραματική μελέτη εφαρμογής του PRP σε δερματικά ελλείμματα διαστάσεων 2x2 εκ., που προκλήθηκαν στα ωτικά πτερύγια είκοσι κονίκλων. Στα ελλείμματα του πτερυγίου του δεξιού ωτός (ομάδα μελέτης) ενείθη ενδοτραυματικά αυτόλογο συμπύκνωμα αιμοπεταλίων και ακολούθησαν τακτικές αλλαγές. Τα ελλείμματα του αριστερού ωτός (ομάδα μαρτύρων) αντιμετωπίστηκαν με τακτικές αλλαγές χωρίς προηγούμενη θεραπεία με PRP. Η παρακολούθηση της επούλωσης των ελλειμμάτων και για τις δύο ομάδες γινόταν με καταγραφή των μορφομετρικών χαρακτηριστικών τους από την αρχή της θεραπείας μέχρι και την 28η ημέρα. Κλινική Μελέτη. Σε χρονικό διάστημα τριών ετών μελετήθηκαν 28 ασθενείς, 16 άνδρες και 12 γυναίκες (μέσος όρος ηλικίας τα 59 έτη), οι οποίοι εμφάνιζαν χρόνιο έλκος για χρονικό διάστημα από 1 έως 13 μήνες (μ.ο. 4,6 μήνες). Σε όλους τους ασθενείς που συμπεριλήφθηκαν στη μελέτη μας είχε εφαρμοσθεί στο παρελθόν ανεπιτυχώς κάποια συντηρητική ή χειρουργική θεραπεία. Η αιτιολογία των ελκών ήταν μηχανική κάκωση (n=14), θερμική κάκωση (n=2), έλκη από κατάκλιση (n=6) και διάσπαση τραύματος (n=6). Η εντόπιση των ελκών αφορούσε στα κάτω άκρα (n=16), στον κορμό (n=10), στα άνω άκρα (n=1) και στην κεφαλή (n=1). Σε όλους τους ασθενείς είχαν προηγηθεί ανεπιτυχώς διάφορες συντηρητικές ή χειρουργικές θεραπείες. Από το σύνολο των ασθενών, οι 10 (ομάδα Α) έφεραν έλκη μεγέθους 10 εκ.² ή/και σταδίου ΙV κατά Shea. Μετά την προετοιμασία του συμπυκνώματος αιμοπεταλίων και τον ήπιο χειρουργικό καθαρισμό του έλκους, ακολουθούσε ενδοτραυματική ένεση του PRP στο έδαφος και τα χείλη του έλκους, με ίση, κατά το δυνατόν, κατανομή στην περιοχή της βλάβης. Η πρόοδος της επούλωσης των ελκών αξιολογήθηκε σε 7 και 14 ημέρες μετά την ένεση του συμπυκνώματος, οπότε και εκτιμήθηκε η ανάγκη περαιτέρω θεραπευτικής -συντηρητικής ή χειρουργικής - αντιμετώπισης. Την καταγραφή των κλινικών χαρακτηριστικών των ελκών συμπλήρωσε η ιστολογική μελέτη. Αποτελέσματα. Η πειραματική μελέτη κατέδειξε ότι 19 από τα 20 έλκη της ομάδας μελέτης επουλώθηκαν κατά β’ σκοπό, σε χρονικό διάστημα 24,9 ημερών κατά μέσο όρο μετά τη θεραπεία με PRP. Στο μη επουλωθέν έλκος της ίδιας ομάδας, η επούλωση εξελισσόταν ομαλά. Από την ομάδα των μαρτύρων, μόνο 7 έλκη ιάθησαν πλήρως, σε χρονικό διάστημα 26,7 ημερών κατά μέσο όρο, ενώ 6 από τα μη ιαθέντα έλκη της ομάδας αυτής παρουσίασαν επιδείνωση, με εμφάνιση ελλείμματος ολικού πάχους του ωτικού πτερυγίου. Όσον αφορά στην κλινική μελέτη, σε 22 ασθενείς έγινε μία εφαρμογή PRP και σε 6 ασθενείς περισσότερες. Από το σύνολο των 28 ελκών, τα 10 έλκη των ασθενών της ομάδας Α ιάθησαν κατά β’ σκοπό σε χρονικό διάστημα επτά εβδομάδων κατά μέσο όρο. Σε 16 από τους ασθενείς της ομάδας Β, η ενδοτραυματική ένεση του PRP βοήθησε στην προετοιμασία του εδάφους του έλκους μέσα σε δύο εβδομάδες, για περαιτέρω αντιμετώπιση. Η χειρουργική αντιμετώπιση που εφαρμόστηκε, ήτοι η μεταμόσχευση δέρματος (n=11) ή η κάλυψη με κρημνό (n=5), ήταν σε κάθε περίπτωση απλούστερη από αυτήν που είχε αρχικά εκτιμηθεί. Σε δύο διαβητικούς ασθενείς της ομάδας Β δεν παρατηρήθηκε καμία κλινική βελτίωση της περιοχής της βλάβης (δάκτυλο ποδιού). Τα αποτελέσματα των ιστολογικών εξετάσεων επιβεβαίωσαν, σε όλες τις περιπτώσεις, τα ανωτέρω κλινικά ευρήματα. Κατά τη διάρκεια των επανελέγχων και έπειτα από παρακολούθηση που εκτεινόταν μέχρι 26 μήνες, δύο μόνο ασθενείς, που έπασχαν από σακχαρώδη διαβήτη, εμφάνισαν υποτροπή του έλκους. Ο πρώτος είχε αντιμετωπισθεί συντηρητικά και ο δεύτερος με τοποθέτηση δερματικού μοσχεύματος μερικού πάχους. Συμπεράσματα. Προτείνεται μία νέα μέθοδος εφαρμογής του συμπυκνώματος αιμοπεταλίων με ενδοτραυματική ένεση, ως εναλλακτική θεραπευτική μέθοδος στην αντιμετώπιση των χρόνιων ελκών. Επιταχύνοντας τη διαδικασία της επούλωσης, η μέθοδος συντελεί είτε στην πλήρη ίαση της βλάβης, είτε στην καλύτερη προετοιμασία του εδάφους του τραύματος για το τελικό στάδιο αποκατάστασης. Η βελτίωση των τοπικών συνθηκών και χαρακτηριστικών του έλκους οδηγεί σε επιλογή επανορθωτικής επέμβασης μικρότερης βαρύτητας για την τελική αποκατάσταση του ελλείμματος και την ταχύτερη αποθεραπεία του ασθενούς, με στατιστικά σημαντική διαφορά

The effect of host tissue and radiation on fat-graft survival: A comparative experimental study

Summary: Because lipofilling is often associated with various reconstructive procedures, especially breast reconstructions, improving fat-graft retention remains a major concern for plastic surgeons. We conducted an experimental protocol in a rat model simulating an autologous breast reconstruction method using the fat-augmented latissimus dorsi myocutaneous (LDM) flap. This study aimed to compare the survival rates of autologous adipocytes when injected subcutaneously and intramuscularly and to evaluate the role of recipient host tissue, volume of the injected fat, and postoperative radiation on fat-graft retention.Thirty rats were divided into five groups (A, B, C, D, and E), of six rats each. All animals underwent a pedicled LDM flap transfer to the anterior thoracic wall, and different volumes of autologous fat were injected into three recipient areas, namely, the pectoralis major and latissimus dorsi muscles and the subcutaneous tissue of the flap's skin island, as follows: 1 mL of fat was injected in total in group A, 2 mL in groups B and D, and 5 mL in group C. Group D animals received postoperative radiation (24 Gy), whereas group E animals (controls) did not undergo any fat grafting procedure. Eight weeks after surgery, adipocyte survival was assessed in all groups using histological and immunochemistry techniques.The results showed that the pectoralis major muscle was the substrate with the highest adipocyte survival rates, which were proportional to the amount of fat injected, followed by the latissimus dorsi muscle and the subcutaneous tissue. Increased volumes of transplanted fat into the subcutaneous tissue did not correspond to increased adipocyte survival. Irradiation of host tissues resulted in a statistically significant decrease in surviving adipocytes in all three recipient sites (p<0.001). Our study strongly suggests that muscle ensures optimal fat-graft retention, whereas postoperative radiation negatively affects adipocyte survival following fat transplantation

Revision breast and chest wall reconstruction in Poland and pectus excavatum following implant complication using free deep inferior epigastric perforator flap

This study aims to present the case of a female patient with Poland′s syndrome and pectus excavatum deformity who underwent breast and chest wall reconstruction with a pre-shaped free deep inferior epigastric perforator flap. A 57-year-old female patient with Poland′s syndrome and pectus excavatum presented with a Baker III capsular contracture following a previously performed implant-based right breast reconstruction. After a chest and abdominal CT angiography, she was staged as 2A1 chest wall deformity according to Park′s classification and underwent implant removal and capsulectomy, followed by a pre-shaped free abdominal flap transfer, providing both breast reconstruction and chest wall deformity correction in a single stage operation. Post-operative course was uneventful, and the aesthetic result remains highly satisfactory 24 months after surgery. Deep inferior epigastric free flap represents an interesting reconstructive solution when treating Poland′s syndrome female patients with chest wall and breast deformities

Predesigned chimeric deep inferior epigastric perforator and inguinal lymph node flap for combined breast and lymphedema reconstruction: A comprehensive algorithmic approach

Summary: The combined use of a deep inferior epigastric perforator (DIEP) flap coupled with vascularized inguinal lymph nodes (VILNs) for simultaneous breast and lymphedema reconstruction has already been well established, and promising results have been reported. However, a standardized approach for the planning and shaping of this combined flap is still lacking. We aimed to propose a comprehensive algorithmic approach for delayed unilateral breast and lymphedema reconstruction using a predesigned abdominal flap associated with inguinal lymph node transfer.We present in detail the preoperative measurements and surgical technique of the chimeric flap, which combines a predesigned DIEP template and a preselected inguinal lymph node flap, based on the preoperative computed tomography angiography and SPEC-CT findings, respectively; four different flap types are described according to the location of the pedicles of the two flap components. Our results of a series of 34 consecutive female patients with unilateral mastectomy and arm lymphedema, who underwent this combined predesigned reconstructive procedure, are retrospectively analyzed and reported.We recorded a high survival rate of the chimeric flaps in our series, with only one case of partial ischemic loss of a DIEP skin island. In the majority of our patients, the pedicles of the combined flaps were located in opposite positions. After a mean 35-month follow-up, we recorded a 47% mean volume difference reduction of the lymphedematous compared to the unaffected arm; no donor-site lymphedema was documented. Self-evaluation questionnaires showed high patient satisfaction rates regarding breast reconstruction. This algorithmic approach provides standardized guidance for accurate design and transfer of the DIEP-VILN chimeric flap while achieving highly satisfactory outcomes for both breast and lymphedema reconstruction

Long-Term Outcomes of Lymph Node Transfer in Secondary Lymphedema and Its Correlation with Flap Characteristics

Background: This retrospective study aimed to assess the impact of certain flap characteristics on long-term outcomes following microsurgical treatment in Breast Cancer-Related Lymphedema (BCRL) patients. Methods: Sixty-four out of 65 BCRL patients, guided by the “Selected Lymph Node” (“SeLyN”) technique, underwent Vascularized Lymph Node Transfer (VLNT) between 2012 and 2018. According to their surface size, flaps were divided into small (2, n = 32) and large (>25 cm2, n = 32). Twelve large and six small flaps were combined with free abdominally based breast reconstruction procedures. Lymphedema stage, flap size, vascular pedicle and number of lymph nodes (LNs) were analyzed in correlation with long-term Volume Differential Reduction (VDR). Results: At 36-month follow-up, no major complication was recorded in 64 cases; one flap failure was excluded from the study. Mean flap size was 27.4 cm2, mean LNs/flap 3.3 and mean VDR 55.7%. Small and large flaps had 2.8 vs. 3.8 LNs/flap (p = 0.001), resulting in 49.6% vs. 61.8% VDR (p = 0.032), respectively. Lymphedema stage and vascular pedicle (SIEA or SCIA/SCIP) had no significant impact on VDR. Conclusion: In our series, larger flaps included a higher number of functional LNs, directly associated with better outcomes as quantified by improved VDR