Effectiveness of an Exercise and Educational-Based Prehabilitation Program in Patients with Breast Cancer Receiving Neoadjuvant Chemotherapy (PREOptimize) on Functional Outcomes: A Randomized Controlled Trial.

OBJECTIVE: The study objective was to determine the effectiveness of a prehabilitation program to decrease postoperative musculoskeletal impairments in patients who have breast cancer and are receiving neoadjuvant therapy (NAT). METHODS: Patients who had breast cancer and were receiving NAT before surgery were invited to participate in this randomized controlled trial. Patients randomized to the intervention group participated in a group-based prehabilitation program consisting of Nordic walking, resistance training, and therapeutic education from month 4 of NAT until before surgery. Patients in the control group received usual care (no prehabilitation). The main outcome was arm function measured with the short version of the Disabilities of the Arm, Shoulder and Hand questionnaire 1 month after surgery. Other measures included pain, range of motion, functional capacity, cancer-related fatigue, handgrip strength, physical activity, and arm circumferences. RESULTS: A total of 64 patients were randomized during the study period, and 61 completed all assessments. A significant difference in the main outcome (short version of the Disabilities of the Arm, Shoulder and Hand questionnaire) was found before surgery as patients in the control group experienced worsening in arm function (mean difference = -9.84, 95% CI = -17.7 to -2). In addition, they also showed increased symptom frequency/severity according to the combined scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30) (mean difference = +6.7 points, 95% CI = 13.4 to 0.1) compared to the intervention group. Prehabilitation also improved functional capacity (mean difference = 67.6 m, 95% CI = 37.4 to 97.7) and physical activity levels and decreased cancer-related fatigue (mean difference = -1.3, 95% CI = -0.29 to -2.4) compared to the control group but had no effect on other secondary outcomes. After surgery, patients receiving prehabilitation also exhibited greater functional capacity at both 1 and 3 months. No other difference was observed. CONCLUSION: A prehabilitation program was able to maintain arm function and increase functional capacity while decreasing fatigue in patients with breast cancer receiving NAT. IMPACT: Prehabilitation programs should be offered to patients with breast cancer to maintain functionality and enhance physical performance before surgery. LAY SUMMARY: An exercise program combined with therapeutic education in patients with breast cancer who receive neoadjuvant therapy before surgery can improve functional capacity and prevent declines of arm mobility and function.

Lymphatic Regeneration after Popliteal Lymph Node Excision and Implantation of Aligned Nanofibrillar Collagen Scaffolds: An Experimental Rabbit Model.

Lymphedema presents significant challenges to patients' quality of life, prompting the exploration of innovative treatments, such as collagen scaffolds, aimed at treating and reducing the risk of lymphedema. We aimed to evaluate the preventive and therapeutic efficacy and the lymphangiogenic potential of implanted aligned nanofibrillar collagen scaffolds (BioBridgeTM) following the induction of secondary lymphedema in a rabbit model. Thirty rabbits were divided into treatment (G1), prevention (G2), and control (G3) groups. Secondary lymphedema was induced in all groups. BioBridgeTM implantation was performed in G2 and G1 on days 0 and 60, respectively. Follow-ups included hindlimb circumference measurements and indocyanine green lymphography at 0, 60, and 90 days. None of the study rabbits exhibited dermal backflow on day 0 before surgery. At 60 days, the incidence rates of dermal backflow in G1, G2, and G3 were 100%, 44.4%, and 90%, respectively. Furthermore, at 90 days, the incidence rates were 22.2%, 44.4%, and 90%, respectively. New linear lymphatic observation was seen in rabbits with resolved dermal backflow. The findings of this study demonstrated the capacity of BioBridgeTM scaffolds to induce new lymphatic vessel formation and reduce dermal backflow in secondary lymphedema in a rabbit model.

Experiences of Patients with Breast Cancer Participating in a Prehabilitation Program: A Qualitative Study.

Background: Breast cancer (BC) is the most prevalent cancer diagnosis among women worldwide. Several randomized controlled trials and systematic reviews have shown the benefits of exercise before, during, and after cancer treatment to manage side effects related to cancer and its therapies. However, these are poorly implemented across the disease-span, specifically, during the preoperative setting. Methods: Patients diagnosed with BC and participating in a randomized controlled trial on the effects of a prehabilitation program based on Nordic walking, muscle strengthening, and therapeutic education were invited to participate in this qualitative substudy. Two groups of eight patients each were recorded, transcript and analyzed using a specialized software (Atlas-Ti®, version 24). Results: During the axial codification phase, 22 unique codes and 6 main themes were identified related to their experience with the program, namely, (1) information received prior to participating; (2) motivation to participate; (3) barriers; (4) facilitators; (5) perceived degree of support from healthcare workers as well as peers; and (6) satisfaction with the characteristics of the prehabilitation program. Conclusions: Patients interviewed showed great interest in prehabilitation as a way to prepare both physically and mentally for surgery. In order to implement these interventions, healthcare systems need to acknowledge barriers and facilitators as well as the need for these programs to be supervised and monitored to avoid adverse events.

Lymphatic Patterns in the Superficial Circumflex Iliac Artery Perforator Flap.

BACKGROUND: Lymphedema is a chronic condition, characterized by fluid buildup and tissue swelling and is caused by impairment of the lymphatic system. The lymph interpositional flap transfer technique, in which lymph flow is restored with a flap that includes subdermal lymphatic channels, is an option for surgical reconstruction. The superficial circumflex iliac artery perforator (SCIP) flap can be used for this purpose. This study aimed to describe and characterize the lymphatic patterns within the vascular territory of the SCIP flap. METHODS: This cross-sectional multicenter study involved 19 healthy volunteers aged ≥18 years of both sexes assessing the bilateral SCIP flap zone. Superficial lymphatic patterns were evaluated at 4-, 14-, and 24 minutes after indocyanine green (ICG) lymphography injection. Standardized procedures were implemented for all participants in both hospitals. RESULTS: The linear pattern was predominant bilaterally. The median number of lymphatic vessels and their length increased over time. Most lymphatic vessels in the SCIP flap were oriented toward the inguinal lymph node (ILN). However, the left SCIP zone lymphatic vessels were directed opposite to the ILN. CONCLUSION: The two sides SCIP zones were not significantly different. The primary direction of the bilateral lymphatic vessels was toward the ILN, although only single-side lymphatic vessels were in the opposite direction. These findings emphasize the importance of assessing lymphatic axiality and coherent lymphatic patterns prior to undertaking the SCIP as an interposition flap, to ensure effective restoration of lymphatic flow.

Lymphaticovenous anastomosis in rabbits: A novel live experimental animal model for supermicrosurgical training.

BACKGROUND: Lymphaticovenous anastomosis is widely used in lymphedema management. Although its effectiveness in reducing edema in patients can be clinically observed, evaluating the long-term outcomes of this technique can be complex. This study established an animal model to assess the outcomes of lymphaticovenous anastomosis technique at 15 and 30-days post-surgery using indocyanine green lymphography, Patent Blue V dye injection, and histopathological examination. METHODS: An experimental model was established in the hindlimbs of 10 rabbits using the popliteal vein and afferent lymphatic vessels in the popliteal area. The subjects were divided into two groups: the first group (n = 5) underwent patency assessment at 0 and 15 days, and the second group (n = 5) at 0 and 30-days, resulting in 20 anastomoses. Patency was verified at 0, 15, and 30-days using indocyanine green lymphography and Patent Blue V injection. Histopathological examinations were performed on the collected anastomosis samples. RESULTS: The patency rate was 90% (19/20) initially, 60% (6/10) at 15 days post-surgery, and 80% (8/10) at 30-days. The average diameter of lymphatic vessels and veins was 1.0 mm and 0.8 mm, respectively. The median number of collateral veins was 3; the median surgical time was 65.8 min. Histopathology revealed minimal endothelial damage and inflammatory responses due to the surgical sutures, with vascular inflammation and thrombosis in a single case. Local vascular neoformations were observed. CONCLUSION: This study highlights the reliability and reproducibility of using rabbits as experimental models for training in lymphaticovenous anastomosis technique owing to the accessibility of the surgical site and dimensions of their popliteal vasculature.

Immediate Partial Breast and Nipple-Areola Complex Reconstruction Using a Superficial Circumflex Iliac Artery Perforator Flap.

The superficial circumflex iliac artery perforator (SCIP) flap is a versatile flap that has been described for various applications, mostly for lower extremity coverage and head and neck reconstructions. However, there are few publications reporting its use for breast reconstruction, mainly because of its low volume availability. In this article, we present the case of a patient who successfully underwent a partial breast and immediate nipple-areola complex (NAC) reconstruction with an SCIP flap. She had been previously reconstructed with an implant after a nipple-sparing mastectomy, but the NAC turned out to be involved with cancer needing further resection. Our goal with this article, is to introduce a novel concept for addressing partial breast and NAC reconstruction and mostly, to illustrate the importance of an adaptable surgical plan based on every individual case emphasizing the versality of microsurgery for breast cancer reconstruction.

Prophylactic lymphedema surgery in lower limb soft tissue sarcomas: A clinical paradigm in a promising field.

INTRODUCTION: Oncological treatments, such as radiotherapy and surgery, are high-risk factors for the development of secondary lymphedema in the upper and lower limbs, as well as the genitalia. Prophylactic lymphedema surgery (PLS) has previously demonstrated promising results in reducing secondary lymphedema in breast cancer and urogenital cancer patients. We conducted a study to adapt this principle for patients with lower-extremity sarcomas. MATERIAL AND METHODS: Inclusion criteria included patients with tumors on the medial aspect of the thigh and leg and tumor size larger than 5 cm. Group A (19 patients) comprised a prospective cohort (2020-2023) in which a PLS protocol was executed. Lymphaticovenous anastomosis (LVA) was performed when lymphatic channels were interrupted due to tumor resection, intraoperatively verified by indocyanine green. Lymph node transfer was employed exclusively in cases involving preoperative radiotherapy and inguinal lymph node resection. Measurements were collected both preoperatively and at 1, 3, 6, and 12 months postoperatively. Group B (26 patients) constituted a retrospective cohort (2017-2020) without PLS reconstruction, where the prevalence of lymphedema was determined. RESULTS: In total, we enrolled 45 patients with soft tissue sarcomas located on the inner aspect of the thigh and leg (26 in the control group vs. 19 in the prophylactic group). In the control group, lymphedema was observed in 10 out of 27 patients (37.04%). In the prophylactic group, two patients exhibited signs of lower-extremity lymphedema (2/19, 10.52%) with a median follow-up of 14.15 months (6 months-33months), demonstrating statistically significant differences between the two groups (p = 0.02931). CONCLUSIONS: PLS for lower limb soft tissue sarcomas shows promising results, although it is premature to reach solid conclusions. Multicentre studies, standardization of criteria, larger sample sizes and longer-term follow-up are imperative for further validation.

Prehabilitation in Patients With Breast Cancer Receiving Neoadjuvant Therapy to Minimize Musculoskeletal Postoperative Complications and Enhance Recovery (PREOPtimize): A Protocol for a Randomized Controlled Trial.

OBJECTIVE: The aim of this study is to assess the effects of a prehabilitation program (PREOPtimize), consisting of Nordic Walking and resistance training exercises plus health education among patients with breast cancer, who are receiving neoadjuvant therapy to enhance postoperative functionality of the affected arm. A secondary aim will be to compare the short-term effects of the intervention on other patient-reported outcome measures. METHODS: This will be an assessor-blind, randomized controlled trial with a parallel group design conducted at a tertiary hospital. A sample of 64 patients with breast cancer scheduled for surgery and undergoing neoadjuvant chemotherapy will be recruited for the trial and randomly allocated to either (1) a prehabilitation program consisting of 2 weekly sessions of 75 minutes of Nordic Walking, muscle strengthening exercises, and health education sessions conducted between the fourth month of treatment and surgery or (2) usual care. Patients in both groups will be assessed at baseline, before surgery, and at 1 and 3 months after surgery. Assessed outcomes include functionality of the affected arm (QuickDash), arm volume, range of motion, handgrip strength, pain, fatigue, functional capacity, physical activity levels, and health-related quality of life. Adherence to the intervention in the prehabilitation group and adverse events will also be recorded. IMPACT: Prehabilitation for patients affected by breast cancer is rarely implemented in clinical practice. The results obtained with the PREOPtimize trial could show that prehabilitation is a feasible intervention for patients with breast cancer receiving neoadjuvant therapy that might enhance postoperative recovery of upper arm function as well as improve overall physical performance and health-related quality of life.

Risk-of-bias assessment of the randomized clinical trials and systematic reviews on surgical treatments for breast cancer-related lymphedema: A mapping review.

BACKGROUND: Breast cancer treatment is the principal cause of lymphedema in the upper extremities. Breast cancer-related lymphedema (BCRL) treatments were previously based on conservative therapy; surgical treatments are alternative options that could be highly beneficial, especially for patients who are not responsive to conservative therapy. The main aim of this study was to describe and critically assess the risk of bias of randomized clinical trials (RCTs) and systematic reviews (SRs) on surgical treatment for BCRL. METHODS: We conducted an evidence mapping review according to the methodology proposed by Global Evidence Mapping (GEM). An update was done for our previous systematic search in MEDLINE, EMBASE, CENTRAL (Cochrane), and Epistemonikos from the year 2000 onward. We assessed the risk of bias for the RCTs and SRs using the RoB-2 and ROBIS tools, respectively. RESULTS: Two surgical RCTs and eight SRs were found among the 47 surgical studies that met the eligibility criteria. The overall risk-of-bias assessments of these studies were rated as some concerns (six outcomes) and high risk (three outcomes) for the measured outcomes among the RCTs and as a high risk of bias (five studies) and low risk (three studies) for the included SRs. CONCLUSIONS: The overall evidence in the literature on surgical treatment for BCRL is low, as there are few published RCTs and SRs, and the risk-of-bias assessment for the majority was rated as high risk of bias or with some concerns. High-quality studies are needed to improve evidence-based decision-making by surgeons and patients.

Temporal validation of a risk prediction model for breast cancer-related lymphoedema in European population: A retrospective study.

AIMS: To perform temporal validation of a risk prediction model for breast cancer-related lymphoedema in the European population. DESIGN: Temporal validation of a previously developed prediction model using a new retrospective cohort of women who had undergone axillary lymph node dissection between June 2018 and June 2020. METHODS: We reviewed clinical records to identify women who did and did not develop lymphoedema within 2 years of surgery and to gather data regarding the variables included in the prediction model. The model was calibrated by calculating Spearman's correlation between observed and expected cases. Its accuracy in discriminating between patients who did versus did not develop lymphoedema was assessed by calculating the area under the receiver operating characteristic curve (AUC). RESULTS: The validation cohort comprised 154 women, 41 of whom developed lymphoedema within 2 years of surgery. The value of Spearman's coefficient indicated a strong correlation between observed and expected cases. Sensitivity of the model was higher than in the derivation cohort, as was the value of the AUC. CONCLUSION: The model shows a good capacity to discriminate women at risk of lymphoedema and may therefore help in developing improved care pathways for individual patients. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: Identifying risk factors for lymphoedema secondary to breast cancer treatment is vital given its impact on women's physical and emotional well-being. IMPACT: What problem did the study address? Risk of BCRL. What were the main findings? The prediction model has a good capacity to discriminate women at risk of lymphoedema. Where and on whom will the research have an impact? In clinical practice with women at risk of BCRL. REPORTING METHOD: STROBE checklist. WHAT DOES THIS PAPER CONTRIBUTE TO THE WIDER GLOBAL CLINICAL COMMUNITY?: It presents a validated risk prediction model for BCRL. NO PATIENT OR PUBLIC CONTRIBUTION: There was no patient or public contribution in the conduct of this study.

Chimeric SCIP flap with iliac bone for reconstruction of foot first ray in a radiated surgical bed: A case report.

Surgical management of sarcoma has evolved from amputation to limb salvage. Nevertheless, subsequent resections in previously irradiated feet are still challenging to reconstruct. First foot ray functional reconstruction is relevant due to its function in weight-bearing and gait. The reconstruction should include a thin, pliable and non-shearing skin paddle with vascularized long cortical bone to mimic the first metatarsal. A clinical case of a 37-year-old patient with a second sarcoma recurrence of the first metatarsal is presented. The patient was irradiated before this new recurrence and had a previous reconstruction with fibula allograft, but subsequently developed a first metatarsal pseudoarthrosis. A wide resection was performed (3.5 cm bone defect) and immediate soft tissue and bone reconstruction with a chimeric SCIP flap with a 17 × 8 cm skin paddle and 3.5 × 1.5 cm iliac bone (cSCIP-IB). At 7 months post-operatively, the patient was able to resumed full weight-bearing. Three years later, remains without disease progression. CSCIP-IB is a good option for foot first ray reconstruction in irradiated beds. This flap has low donor site morbidity and a higher ossification success rate compared to bone allografts.

Popliteal Vascular Lymph Node Resection in the Rabbit Hindlimb for Secondary Lymphedema Induction.

Lymphedema is a common condition often associated with cancer and its treatment, which leads to damage to the lymphatic system, and current treatments are mostly palliative rather than curative. Its high incidence among oncologic patients indicates the need to study both normal lymphatic function and pathologic dysfunction. To reproduce chronic lymphedema, it is necessary to choose a suitable experimental animal. Attempts to establish animal models are limited by the regenerative capacity of the lymphatic system. Among the potential candidates, the rabbit hindlimb is easy to handle and extrapolate to the human clinical scenario, making it advantageous. In addition, the size of this species allows for better selection of lymphatic vessels for vascularized lymph node resection. In this study, we present a procedure of vascular lymph node resection in the rabbit hindlimb for inducing secondary lymphedema. Anesthetized animals were subjected to circumferential measurement, patent blue V infiltration, and indocyanine green lymphography (ICG-L) using real-time near-infrared fluorescence, a technique that allows the identification of single popliteal nodes and lymphatic channels. Access to the identified structures is achieved by excising the popliteal node and ligating the medial and lateral afferent lymphatics. Special care must be taken to ensure that any lymphatic vessel that joins the femoral lymphatic system within the thigh without entering the popliteal node can be identified and ligated. Postoperative evaluation was performed at 3, 6, and 12 months after induction using circumferential measurements of the hindlimb and ICG-L. As demonstrated during follow-up, the animals developed dermal backflow that was maintained until the 12th month, making this experimental animal useful for novel long-term evaluations in the management of lymphedema. In conclusion, the approach described here is feasible and reproducible. Additionally, during the time window presented, it can be representative of human lymphedema, thus providing a useful research tool.

Use of fluorescence imaging during lymphatic surgery: A Delphi survey of experts worldwide.

BACKGROUND: Fluorescence imaging with indocyanine green is increasingly used during lymphedema patient management. However, to date, no guidelines exist on when it should and should not be used or how it should be performed. Our objective was to have an international panel of experts identify areas of consensus and nonconsensus in current attitudes and practices in fluorescence imaging with indocyanine green use during lymphedema surgery patient management. METHODS: A 2-round Delphi study was conducted involving 18 experts in the use of fluorescence imaging during lymphatic surgery, all asked to vote on 49 statements on patient preparation and contraindications (n = 7 statements), indocyanine green dosing and administration (n = 10), fluorescence imaging uses and potential advantages (n = 16), and potential disadvantages and training needs (n = 16). RESULTS: Consensus ultimately was reached on 40/49 statements, including consistent consensus regarding the value of fluorescence imaging with indocyanine green in almost all facets of lymphedema patient management, including early detection, assessing disease extent, preoperative work-up, surgical planning, intraoperative guidance, monitoring short- and longer-term outcomes, quality control, and resident training. All experts felt it was very safe, while 94% felt it should be part of routine care and that indocyanine green was superior to colored dyes and ultrasound. Nonetheless, there also was consensus that limited high-quality evidence remains a barrier to its widespread use and that patients should still be provided with specific information and asked to sign specific consent for both fluorescence imaging and indocyanine green. CONCLUSION: Fluorescence imaging with or without indocyanine green appears to have several roles in lymphedema prevention, diagnosis, assessment, and treatment.

Delphi survey of intercontinental experts to identify areas of consensus on the use of indocyanine green angiography for tissue perfusion assessment during plastic and reconstructive surgery.

BACKGROUND: In recent years, indocyanine green angiography (ICG-A) has been used increasingly to assist tissue perfusion assessments during plastic and reconstructive surgery procedures, but no guidelines exist regarding its use. We sought to identify areas of consensus and non-consensus among international experts on the use of ICG-A for tissue-perfusion assessments during plastic and reconstructive surgery. METHODS: A two-round, online Delphi survey was conducted of 22 international experts from four continents asking them to vote on 79 statements divided into five modules: module 1 = patient preparation and contraindications (n = 11 statements); module 2 = ICG administration and camera settings (n = 17); module 3 = other factors impacting perfusion assessments (n = 10); module 4 = specific indications, including trauma debridement (n = 9), mastectomy skin flaps (n = 6), and free flap reconstruction (n = 8); and module 5 = general advantages and disadvantages, training, insurance coverage issues, and future directions (n = 18). Consensus was defined as ≥70% inter-voter agreement. RESULTS: Consensus was reached on 73/79 statements, including the overall value, advantages, and limitations of ICG-A in numerous surgical settings; also, on the dose (0.05 mg/kg) and timing of ICG administration (∼20-60 seconds preassessment) and best camera angle (61-90o) and target-to-tissue distance (20-30 cm). However, consensus also was reached that camera angle and distance can vary, depending on the make of camera, and that further research is necessary to technically optimize this imaging tool. The experts also agreed that ambient light, patient body temperature, and vasopressor use impact perfusion assessments. CONCLUSION: ICG-A aids perfusion assessments during plastic and reconstructive surgery and should no longer be considered experimental. It has become an important surgical tool.