Comparing the Impact of Diluents and Injection Techniques on Patient Comfort During Indocyanine Green Lymphangiography: A Prospective Study.

Background: Indocyanine green (ICG) lymphography, a key diagnostic tool for lymphedema, is influenced by the dilution process of ICG dye, impacting patient experience. Methods and Results: In our study, we assessed three different ICG diluents-water for injection (WFI), normal saline (NS), and Dextrose® plus human albumin-in five healthy volunteer individuals undergoing superficial lymphography of the upper limb over 3 weeks. Results indicated that NS, as a diluent for ICG, caused the least discomfort during injection, in contrast to WFI, which led to the highest levels of discomfort. Transport time of ICG from the injection site to the axillary lymph nodes was notably shorter in intradermal injections than in subdermal injections. Conclusion: Our findings advocate for using NS as the optimal and cost-effective diluent for ICG, enhancing patient experience.

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

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.

Treatment of Rat Lymphedema by Propeller Lymphatic Tissue Flap Combined with Nanofibrillar Collagen Scaffolds.

BACKGROUND: The aim of our study was to evaluate a new propeller vascularized lymphatic tissue flap (pVLNT) combined with aligned nanofibrillar collagen scaffolds (CS) (BioBridge) in reducing lymphedema in the rat lymphedema model. METHODS: Unilateral left hindlimb lymphedema was created in 15 female Sprague-Dawley rats following inguinal and popliteal lymph nodes (LN) resection and radiation. An inguinal pVLNT was elevated from the contralateral groin and transferred through a skin tunnel to the affected groin. Four collagen threads were attached to the flap and inserted in the hindlimb at the subcutaneous level in a fan shape. The three study groups consisted of group A (control), group B (pVLNT), and group C (pVLNT + CS). Volumetric analysis of both hindlimbs was performed using micro-computed tomography imaging before the surgery (at initial time point) and then at 1 and 4 months, postoperatively, and the relative volume difference (excess volume) was measured for each animal. Lymphatic drainage was assessed by indocyanine green (ICG) fluoroscopy for number and morphology of new collectors and the time required for ICG to move from injection point to the midline. RESULTS: Four months after the induction of lymphedema, an increased relative volume difference remained in group A (5.32 ± 4.74%), while there was a significant relative volume reduction in group B (-13.39 ± 8.55%) and an even greater reduction in group C (-14.56 ± 5.04%). ICG fluoroscopy proved the functional restoration of lymphatic vessels and viability of pVLNT in both B and C groups. Notably, only group C demonstrated statistically significant improvements in lymphatic pattern/morphology and in the number of lymphatic collectors as compared with the control group A. CONCLUSION: The pedicle lymphatic tissue flap combined with SC is an effective procedure for the treatment of lymphedema in rats. It can be easily translated into treatment of humans' lower and upper limb lymphedema and further clinical studies are warranted.

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

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.

Development of a rat model of lymphedema and the implantation of a collagen-based medical device for therapeutic intervention.

Secondary lymphedema is a common condition among cancer survivors, and treatment strategies to prevent or treat lymphedema are in high demand. The development of novel strategies to diagnose or treat lymphedema would benefit from a robust experimental animal model of secondary lymphedema. The purpose of this methods paper is to describe and summarize our experience in developing and characterizing a rat hindlimb model of lymphedema. Here we describe a protocol to induce secondary lymphedema that takes advantage of micro computed tomography imaging for limb volume measurements and visualization of lymph drainage with near infrared imaging. To demonstrate the utility of this preclinical model for studying the therapeutic benefit of novel devices, we apply this animal model to test the efficacy of a biomaterials-based implantable medical device.

Consecutive bilateral breast reconstruction using different autologous flaps: can symmetrical results still be achieved? A case report.

We report a 60-year-old patient who underwent bilateral mastectomy at different times, followed by immediate autologous reconstruction with different flaps: deep-inferior epigastric-perforator flap on one breast, and fat-augmented latissimus dorsi on the contralateral side. At 20-month follow-up, good symmetry was recorded; patient-reported outcome measurements revealed high satisfaction scores.

Simultaneous upper limb melanoma and breast cancer related lymphedema management.

We present a rare case of a patient with malignant melanoma in the lymphedematous arm associated with breast cancer and its lymphedema management. Histology of previous lymphadenectomy and results of current lymphangiographies suggested the need for SLN biopsy, and simultaneously perform of distal LVAs to manage lymphedema.

Investigation of Autologous Fat Transfer in Capsule Formation around Silicone Implants in a Rat Model.

BACKGROUND: In this experimental study, the authors investigated whether fat placement in the pocket during implant insertion affects capsule formation. METHODS: Twenty albino Wistar rats, 400 g each, were used. The rats were divided into two groups, A and B, of 10 rats each. At the dorsum of each rat, four pockets (2 × 2 cm each) were dissected, two left and two right of the midline. In each pocket, a 1 × 1 × 1.5-cm silicone implant was inserted. In the two left pockets, only silicone implants were placed (control). In the two right pockets, 0.4 ml of fat was injected around the implant. Animals in group A were killed 2 months postoperatively, and those in group B were killed 4 months postoperatively. The implants were dissected with the capsule and sent for histopathologic examination. RESULTS: The data of the fat transfer group was compared with control in groups A and B. Capsule thickness, neovascularization, myofibroblast layer thickness, and mast cell population demonstrated no statistically significant difference in either group A (p = 0.385, p = 0.862, p = 0.874, and p = 0.210, respectively) or group B (p = 0.338, p = 1.000, p = 0.288, and p = 0.344, respectively). Inflammation was statistically significantly less (p = 0.07) at 4 months (group B) in the fat transfer group compared to the control group. Likewise, cellularity was statistically significantly less (p = 0.019) at 4 months for the fat transfer group compared with the control group. CONCLUSION: Fat injection in the pocket during implant placement may reduce inflammation and cellularity of capsules and predispose to faster capsule maturation. CLINICAL RELEVANCE STATEMENT: Fat transfer around implants may positively affect implant-based breast reconstruction and/or breast augmentation.

Genetic Predisposition in Cancer-Related Lymphedema: A Systematic Review.

Background: Lymphedema is a debilitating and progressive clinical entity characterized by abnormal accumulation of lymph and fluid in the extracellular space. Most of the cases in western population are related to cancer treatment. Research on cancer-related lymphedema (CRL) is mounting for potential risk factors associated to disease, treatment, or patient. However, only a few cancer survivors with the same risk factors will develop lymphedema, giving rise to the hypothesis that inherited genetic susceptibility may play a role in CRL pathophysiology. This systematic review aimed to identify, critically appraise, and summarize the results of individual studies that have examined the genetic predisposition to CRL. Methods and Results: A comprehensive literature search in MEDLINE, Cochrane, and Scopus was conducted from inception to February 2021. Screening of available studies and quality of the included studies were carried out by two reviewers independently. Eight studies fulfilled eligibility criteria, involving 573 women with breast-cancer related lymphedema (BCRL) among 1,481 participants. Associations between the development of CRL and genetic factors were observed for variations in 23 genes in patients with BCRL. Conclusions: The present systematic review is the first examining specifically the genetic predisposition in CRL. Statistically significant genetic variations were found in 23 genes in patients with BCRL. These preliminary findings highlight the importance of genetic susceptibility in the development of CRL, altering the traditional perception of its iatrogenic etiology. Additional well-designed research, aiming toward the confirmation of previously performed genetic analyses and functional assessment of the genetic variations, is required.

Lymphatic regeneration after implantation of aligned nanofibrillar collagen scaffolds: Preliminary preclinical and clinical results.

BACKGROUND: We tested our hypothesis that implantation of aligned nanofibrillar collagen scaffolds (BioBridge™) can both prevent and reduce established lymphedema in the rat lymphedema model. Our authors report clinical cases that demonstrate new lymphatic formation guided by BioBridge™ as seen by near-infrared (NIR) fluoroscopy and magnetic resonance (MR) lymphography. METHODS: A rat lymphedema model was utilized. A prevention group received implantation of BioBridge™ immediately after lymphadenectomy. A lymphedema group received implantation of BioBridge™ with autologous adipose-derived stem cells (ADSC; treatment group) or remained untreated (control group). All subjects were observed for 4 months after lymphadenectomy. The hindlimb change was evaluated using computed tomography-based volumetric analysis. Lymphagiogenesis was assessed by indocyanine green (ICG) lymphography. RESULTS: Animals in the treatment group showed a reduction in affected limb volume. Animals in the prevention group showed no increase in the affected limb volume. ICG fluoroscopy demonstrated lymph flow and formation of lymphatics toward healthy lymphatics. CONCLUSIONS: In the rat lymphedema model, implantation of BioBridge™ at the time of lymph node removal prevents the development of lymphedema. Treatment of established lymphedema with the BioBridge™ and ADSC reduces lymphedema. New lymphatic vessels are demonstrated by NIR fluoroscopy and MR lymphography. These findings have implications for the treatment of lymphedema in human subjects.

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 (<25 cm2, 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.

Fat-Augmented Latissimus Dorsi versus Deep Inferior Epigastric Perforator Flap: Comparative Study in Delayed Autologous Breast Reconstruction.

BACKGROUND: The use of autologous tissues is considered the mainstay for delayed breast reconstruction. Aside the free abdominal flaps, which are most commonly used, the fat-augmented latissimus-dorsi (FALD) flap has been recently shown a reliable alternative option for pure autologous breast reconstruction. In this retrospective study, we aim to compare outcomes of autologous breast reconstructions using the extended FALD and deep inferior epigastric perforator flap (DIEP) flap, with an emphasis on patients' characteristics, demographic data, complications, and patients' satisfaction after a minimum 12-month follow-up. METHODS: Our series consists of 135 women who underwent a delayed postmastectomy unilateral autologous breast reconstruction from 2011 to 2017: 36 patients (Group A) had an extended FALD flap and 99 (Group B) a free DIEP flap performed by the same surgeons. Demographic data, breast volume, medical history, smoking, complications, and patients' satisfaction were recorded and analyzed. Student's t-test for independent variables, Mann-Whitney U-test, and Chi-squared test were used to compare the reported variables. RESULTS: Patients' age, body mass index (BMI), and pregnancy history were statistically different between groups (p < 0.001, p = 0.004, p < 0.001, respectively); younger age (35.1 vs. 41.2 years), lower BMI (25.6 vs. 28.4), and fewer pregnancies were recorded in Group A. Breast volume was also found significantly smaller in Group A patients (p = 0.009). Past medical history using the ASA physical status classification score, previous radiation therapy, history of smoking, and incidence of overall complications were similar in both groups. Overall satisfaction scores were found slightly higher, but not statistically significant, in the free-flap group (p = 0.442). CONCLUSION: The use of the FALD flap may provide comparable outcome to the DIEP flap in delayed breast reconstruction in terms of complications and patients' satisfaction; it should be considered a good reconstructive option for young and thin nulliparous patients, with small to medium size opposite breast.

Evolution and refinements of a dorsal adipofascial digital artery perforator flap.

BACKGROUND: Soft tissue defects to the dorsum of fingers are quite demanding for the reconstructive surgeon especially in the cases that bone and extensor tendons are exposed. The purpose of our study was to describe a new adipofascial island flap by a single dorsal digital perforator (dorsal adipofascial digital artery perforator, DADAP). MATERIALS: Methods: In 8 patients (7 male, 1 female), 12 soft tissue defects to the dorsum of the fingers (3 index, 6 middle, 2 ring, 1 little finger), ranging from 1 × 2 cm to 2 × 4 cm, were reconstructed using the DADAP flap. RESULTS: The flaps sizes ranged from 2.5 × 1.5 cm to 8 × 3 cm. The defects were covered in 9 cases by a propeller-rotation type flap and in 3 by a turn-over flap. In 4 cases a tendon graft was used to cover the tendon defect and in 3 cases an open joint was reconstructed. In all cases a splint thickness skin graft (SSG) covered the flaps. Mean follow-up was 18 months. One patient developed distal tip flap necrosis and was treated conservatively. Delayed wound healing with partial SSG failure due to haematoma was observed in 3 fingers, but the underlying flap was viable and complete healing was achieved by secondary intention. CONCLUSIONS: The use of DADAP flap is a fast, safe and reliable solution to cover the defects of the dorsum of fingers and can be performed under local anaesthesia as a day surgery.

Reverse neurocutaneous vs propeller perforator flaps in diabetic foot reconstruction.

Introduction Reverse neurocutaneous and propeller perforator flaps are both used to reconstruct diabetic distal lower limb defects. Our study aims to compare outcomes between these two groups of flaps with an emphasis on indications and complication rates. Method A retrospective analysis was conducted, reviewing data from 54 diabetic patients who underwent reconstruction of acute or chronic wounds of the foot and ankle between 2005-2018. Thirty-four patients (Group A) had a reverse neurocutaneous flap (NCF): nineteen sural and fifteen lateral supramalleolar flaps. Twenty patients (Group B) had a propeller flap (PF) based on peroneal (n = 13) or posterior tibial artery perforators (n = 7). All patients had a preoperative Doppler examination to identify the nutrient artery of the flap. In both groups, we recorded patients' demographics, characteristics of the defect, postoperative complications and time to heal. Follow-up ranged from 6 to 59 months. Student's t-test and chi-squared test were used for statistical analysis. Results Mean patients' age was 59.1 and 50.8 years for Group A and B, respectively. Defects were located at the Achilles zone (n = 16), posterior heel (n = 14), foot dorsum (n = 9), lateral and medial malleolar areas (n = 8), anterior ankle (n = 5) and lateral foot (n = 2). Mean size of the defect was 42.8 cm2 in Group A and 23 cm2 in Group B. Uneventful healing was recorded in 20/34 neurocutaneous flaps and in 12/20 propeller flaps; complications included two complete flap losses (one NCF, one PF), seventeen distal flap necroses (10 NCFs, 7 PFs), fifteen delayed wound healing events over the donor or recipient site (12 NCFs, 3 PFs). Secondary surgeries were required in 15 NCF and 8 PF patients. Mean healing time was 48.1 and 40.7 days for Group A and B, respectively. All patients, except one NCF case, which resulted in leg amputation, returned to previous levels of ambulation. Conclusion Reverse neurocutaneous and propeller flaps may provide stable reconstruction of diabetic lower limb defects; neurocutaneous flaps are specially indicated for larger and more distally located defects, although they might be associated with longer healing time and additional revision surgeries. Propeller flaps were more frequently used in younger patients for smaller and more proximally located defects.

Functional lymphatic reconstruction with the "Selected Lymph Node" technique guided by a SPECT-CT lymphoscintigraphy.

BACKGROUND: A new technique named "Selected Lymph Node" ("SeLyN") was evaluated, aiming to identify the most functional groin lymph nodes (LNs) for an effective LN transplantation. METHODS: Bilateral lower-limb SPECT-CT was performed in the upper-limb lymphedema patients, to select the most radioactive inguinal LN. Recorded data included demographics, stage, etiology of lymphedema, flap consistency in accordance to preoperative findings, flap size, number of LN, and harvesting time. Infection episodes per year and volume changes of the upper limbs were documented. Donor-site complications were recorded and lower-limb evaluation was performed through clinical examination, volume analysis, and lymphoscintigraphy. RESULTS: A total of 41 patients underwent a "SeLyN" transfer technique. The mean flap size was 28.34 cm2 containing a mean of 3.4 LNs. The mean time spent on flap harvest was 39 minutes. A mean 56.5% volume reduction (P < .001) and a mean 1.41 to 0.29 infection episodes per patient per year (P < .001) were recorded. Clinical evaluation and lymphography of the donor site advocated no major complications for a mean follow-up period of 42.5 months. CONCLUSIONS: "SeLyN" is a safe and effective technique in selecting the most suitable LNs, minimizing the donor-site morbidity, and decreasing the overall operating time.

Outcomes of Fat-Augmented Latissimus Dorsi (FALD) Flap Versus Implant-Based Latissimus Dorsi Flap for Delayed Post-radiation Breast Reconstruction.

BACKGROUND: Although free abdominal flaps constitute the gold standard in post-radiation delayed breast reconstruction, latissimus dorsi-based methods offer alternative reconstructive options. This retrospective study aims to compare outcomes of delayed breast reconstruction using the fat-augmented latissimus dorsi (FALD) autologous reconstruction and the latissimus dorsi-plus-implant reconstruction in irradiated women. METHODS: We reviewed the files of 47 post-mastectomy irradiated patients (aged 29-73 years), who underwent delayed latissimus dorsi-based breast reconstruction between 2010 and 2016. Twenty-three patients (Group A) had an extended FALD flap and twenty-four patients (Group B) an implant-based latissimus dorsi reconstruction. Patients' age, BMI, pregnancies, volume of injected fat, implant size, postoperative complications, and secondary surgical procedures were recorded and analyzed. RESULTS: Age, BMI, pregnancies, and donor-site complications were similar in both groups (p > 0.05). Mean fat volume injected initially was 254 cc (ranged 130-380 cc/session); mean implant volume was 323 cc (ranged 225-420 cc). Breast complications were significantly fewer in Group A (one wound dehiscence, two oily cysts) compared to Group B (three cases with wound dehiscence, two extrusions, thirteen severe capsular contractions). Non-statistically significant difference was documented for secondary procedures between groups; although the mean number of additional surgeries/patient was higher in Group A, they referred to secondary lipofilling, whereas in Group B they were revision surgeries for complications. CONCLUSIONS: The FALD flap constitutes an alternative method for delayed autologous reconstruction after post-mastectomy irradiation, avoiding implant-related complications. Although additional fat graft sessions might be required, it provides an ideal autogenous reconstructive option for thin nulliparous women, with a small opposite breast and adequate fat donor sites. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Donor-Site Lymphedema Following Lymph Node Transfer for Breast Cancer-Related Lymphedema: A Systematic Review of the Literature.

Abstracts Background: Among current surgical options used for treating breast cancer-related lymphedema (BCRL), autologous lymph node transfer (ALNT) is shown to provide favorable results. However, postoperative donor-site lymphedema (DSL), following the lymphatic flap harvesting from the groin area, has already been reported. Our aim is to summarize the recent literature for evidence of DSL following an ALNT for BCRL. METHODS AND RESULTS: A PubMed bibliographic search was performed for published studies evaluating donor-site complications following LNT in BCRL patients. We recorded demographic data of the patients, the type of flap used, the follow-up, the donor-site morbidity, and the diagnostic tests performed pre- and postoperatively. Statistical analysis was conducted to document any correlation between the incidence of DSL and the abovementioned recorded parameters. According to our results, 11 studies met the inclusion criteria. From a total of 189 patients, three cases with DSL of the lower limb were reported (1.6%). No statistically significant correlations were found. CONCLUSION: ALNT has become increasingly popular and is considered an effective surgical option for treating BCRL of the upper limb. Although the incidence of postoperative DSL is low, insufficient data on patients' demographics, surgical details, and postoperative assessment do not allow extracting significant correlations. Meticulous technique of lymph node harvesting should be seriously considered to further minimize this infrequent but debilitating complication.