Concordance between preoperative imaging methods in patients with limb lymphedema undergoing supermicrosurgical lymphaticovenular anastomosis.

OBJECTIVE: Supermicrosurgical lymphaticovenular anastomosis (LVA) is increasingly being recognized as a first-line treatment of limb lymphedema because it is minimally invasive and highly effective. Lymphoscintigraphy and indocyanine green (ICG) lymphography are the two most commonly performed diagnostic imaging examinations to establish the indication and plan the procedure for patients affected by limb lymphedema. In a small group of patients, the information between these two imaging tools can be discordant, showing different anatomical drainage pathways or the absence of drainage and dermal backflow in one examination and valid drainage pathways in the other. The purpose of this study is to examine the types of possible discrepancies between lymphoscintigraphy of the superficial system and ICG lymphography and to describe the surgical outcomes after LVA for patients presenting with such discrepancies. METHODS: We retrospectively reviewed the data of all patients who underwent LVA for upper or lower limb lymphedema between July 2015 and July 2023. From this series, we identified a group of patients with nonconcordant imaging results from lymphoscintigraphy and ICG lymphography before lymphatic surgery. Nonconcordant findings were described in terms of "pattern discordance" and "pathway discordance." The surgical outcome was measured by the change in the mean circumference of the limb after surgery. The changes between the preoperative and postoperative limb measures were analyzed using the Student t test. P values < .05 were considered significant. RESULTS: A total of 28 patients with limb lymphedema exhibited inconsistencies between preoperative lymphoscintigraphy of the superficial system and ICG lymphography. Among these patients, 14 experienced pattern discordance, 13 had pathway discordance, and 1 patient had both. After LVA, we observed a significant reduction in the average circumference of the affected limb in the analyzed group. CONCLUSIONS: The discrepancy in the information between lymphoscintigraphy and ICG lymphography in the preoperative study of patients affected by limb lymphedema is rare but possible. This phenomenon is still not fully explained; however, our results suggest that it does not correlate with the outcome of supermicrosurgical LVAs.

The Role of Postoperative Radiotherapy in the Management of Dermatofibrosarcoma Protuberans: A Multidisciplinary Systematic Review.

Background: Dermatofibrosarcoma protuberans (DFSP) is a superficial soft tissue sarcoma, and surgical excision is the first-line treatment. The aim of this systematic review is to provide an update about the current indications and clinical results regarding the use of postoperative radiotherapy in DSFP, considering both adjuvant and salvage setting. Methods: We conducted a systematic literature review using the main scientific database, including Cochrane library, Scopus, and PubMed, for any relevant article about the topic, and we considered all available papers without any time restriction. Results: Twenty-two papers, published between 1989 and 2023, were retrieved and considered eligible for inclusion in this review. Regarding the fractionation schedules, most authors reported using standard fractionation (2 Gy/die) with a wide total dose ranging from 50 to 70 Gy. The local control after postoperative radiotherapy was excellent (75-100%), with a median follow-up time of 69 months. Conclusions: After the primary surgical management of DFSP, postoperative radiotherapy may either be considered as adjuvant treatment (presence of risk factors, i.e., close margins, recurrent tumours, aggressive histological subtypes) or as salvage treatment (positive margins) and should be assessed within the frame of multidisciplinary evaluation.

Tunnelised superiorly based preauricular flap and conchal cartilage graft for antihelix reconstruction.

Reconstruction of a full-thickness defect of the auricle's anterior surface represents a challenge for plastic surgeons. This report describes the case of a man in his 70s, who underwent radical excision of a squamous cell carcinoma involving his right antihelix. We adopted an innovative approach for the reconstruction of the antihelix, using a tunnelled preauricular flap reinforced with an ipsilateral concha cartilage graft. The flap's base was de-epithelialised, allowing a single-stage procedure. Three months postoperation, no complications arose, and the scars at the donor site were effectively concealed. The aesthetic result was excellent, thanks to the perfect colour match, symmetry, shape of the auricle and the long-lasting integrity of the antihelical structure.This technique allows for accurate reconstruction of the convoluted surface of the auricle in cases of full-thickness defects of the antihelix, without the need to harvest cartilage from other donor sites and in a single surgical procedure.

Comprehensive Criteria for Differential Diagnosis and a Surgical Management Algorithm for Occipital Neuralgia and Migraine Headaches.

The differential diagnoses and nuances of the surgical management of occipital migraine and occipital neuralgia have not been clearly discussed in the available literature. This study aims to highlight additional diagnostic features and offers an algorithm for the surgical treatment of occipital migraine and occipital neuralgia based on the vast experience of the senior author spanning over 23 years. A retrospective cohort study was conducted to review the number and distribution of patients who underwent surgical treatment for occipital migraine headaches and neuralgia and the signs and symptoms observed. Among the 660 patients who underwent surgical treatment for headaches within the territory of the greater occipital nerves, 86 patients underwent isolated deactivation of the greater occipital site (site IV) or combined greater and lesser occipital sites (site IV and site VI surgical). Within the isolated occipital headache group, 43 patients met the criteria for migraine headaches and 43 for occipital neuralgia. Our additional observation on the differences between the occipital neuralgia and migraine groups included that occipital neuralgia is more commonly unilateral, less commonly familial, and more commonly associated with a whiplash-type injury. In addition, the patient with occipital neuralgia can consistently identify the distinct point of pain using the index finger. An ultrasound Doppler signal can also be detected at the pain site and a pulse is often palpable in the site identified by the patient. Occipital neuralgia is also commonly continuous and unrelenting, with occasional spikes of shooting pain, and is less likely to respond to botulinum toxin-A injection. Patients with occipital neuralgia often have a single-site headache while patients with migraine headaches often suffer from headaches in multiple sites. Additional clinical criteria are offered for the differential diagnosis of occipital migraine headaches and occipital neuralgia based on the vast experience of the senior author and the developed surgical management algorithm.

Double Lateral Osteotomy: Not Only the Correction of Crooked Noses but a Relevant Aesthetical Refinement in Structural Rhinoplasty.

BACKGROUND: Osteotomy represents a crucial step in structural rhinoplasty; however, there is not a unique approach accepted. Double lateral osteotomy has proven to be effective in the long-term correction of a deviated nose. In this series, we evaluated its aesthetic value also in non-deviated cases. MATERIALS AND METHODS: 864 patients who underwent primary structural rhinoplasty from 2012 to 2020 were divided into four groups. Group A and B included patients with a crooked nose treated with asymmetrical double osteotomy and bilateral double osteotomy, respectively. Patients who did not present nasal deviation were divided into group C, including cases treated with bilateral single osteotomy, and group D, including patients who underwent bilateral double osteotomy. Postoperative evaluations were performed by three independent plastic surgeons blinded to the surgical technique. Patient's satisfaction was assessed through the FACE-Q rhinoplasty module. RESULTS: FACE-Q scores reported a satisfaction rate higher than 30% for every item in all groups; however, group B and group D showed statistically higher satisfaction (p < 0.01). According to the evaluations performed by physicians, group B and group D showed the most satisfactory outcomes (p < 0.01). CONCLUSIONS: bilateral double osteotomies represent a significant aesthetic refinement in structural rhinoplasty, not only in crooked noses but also in non-deviated cases, since the reduction in the width of the nose is an aesthetical aspect very appreciated by patients.

Secondary post-oncologic vulvar reconstruction - a simplified algorithm.

Introduction: Surgical treatment is the gold standard of care for vulvar cancer and is burdened by a high risk of wound complications due to the poor healing typical of the female genital area. Moreover, this malignancy has a high risk of local relapse even after wide excision. For these reasons, secondary reconstruction of the vulvoperineal area is a relevant and challenging scenario for gynecologists and plastic surgeons. The presence of tissue already operated on and undermined, scars, incisions, the possibility of previous radiation therapy, contamination of urinary and fecal pathogens in the dehiscent wound or ulcerated tumor, and the unavailability of some flaps employed during the primary procedure are typical complexities of this surgery. Due to the rarity of this tumor, a rational approach to secondary reconstruction has never been proposed in the literature. Methods: In this observational retrospective study, we reviewed the clinical data of patients affected by vulvar cancer who underwent secondary reconstruction of the vulvoperineal area in our hospital between 2013 and 2023. Oncological, reconstructive, demographic, and complication data were recorded. The primary outcome measure was the incidence of wound complications. The secondary outcome measure was the indication of the different flaps, according to the defect, to establish an algorithm for decision-making. Results: Sixty-six patients were included; mean age was 71.3 ± 9.4 years, and the mean BMI was 25.1 ± 4.9. The mean size of the defect repaired by secondary vulvar reconstruction was 178 cm2 ± 163 cm2. Vertical rectus abdominis myocutaneous (VRAM), anterolateral thigh (ALT), fasciocutaneous V-Y (VY), and deep inferior epigastric perforator (DIEP) were the flaps more frequently employed. We observed five cases of wound breakdown, one case of marginal necrosis of an ALT flap, and three cases of wound infection. The algorithm we developed considered the geometry and size of the defect and the flaps still available after previous surgery. Discussion: A systematic approach to secondary vulvar reconstruction can provide good surgical results with a low rate of complications. The geometry of the defect and the use of both traditional and perforator flaps should guide the choice of the reconstructive technique.

Agonist of growth hormone-releasing hormone improves the disease features of spinal muscular atrophy mice.

Spinal muscular atrophy (SMA) is a severe autosomal recessive neuromuscular disease affecting children and young adults, caused by mutations of the survival motor neuron 1 gene (SMN1). SMA is characterized by the degeneration of spinal alpha motor neurons (αMNs), associated with muscle paralysis and atrophy, as well as other peripheral alterations. Both growth hormone-releasing hormone (GHRH) and its potent agonistic analog, MR-409, exert protective effects on muscle atrophy, cardiomyopathies, ischemic stroke, and inflammation. In this study, we aimed to assess the protective role of MR-409 in SMNΔ7 mice, a widely used model of SMA. Daily subcutaneous treatment with MR-409 (1 or 2 mg/kg), from postnatal day 2 (P2) to euthanization (P12), increased body weight and improved motor behavior in SMA mice, particularly at the highest dose tested. In addition, MR-409 reduced atrophy and ameliorated trophism in quadriceps and gastrocnemius muscles, as determined by an increase in fiber size, as well as upregulation of myogenic genes and inhibition of proteolytic pathways. MR-409 also promoted the maturation of neuromuscular junctions, by reducing multi-innervated endplates and increasing those mono-innervated. Finally, treatment with MR-409 delayed αMN death and blunted neuroinflammation in the spinal cord of SMA mice. In conclusion, the present study demonstrates that MR-409 has protective effects in SMNΔ7 mice, suggesting that GHRH agonists are promising agents for the treatment of SMA, possibly in combination with SMN-dependent strategies.

Bicalutamide and Trehalose Ameliorate Spinal and Bulbar Muscular Atrophy Pathology in Mice.

Spinal and bulbar muscular atrophy (SBMA) is characterized by motor neuron (MN) degeneration that leads to slowly progressive muscle weakness. It is considered a neuromuscular disease since muscle has a primary role in disease onset and progression. SBMA is caused by a CAG triplet repeat expansion in the androgen receptor (AR) gene. The translated poly-glutamine (polyQ) tract confers a toxic gain of function to the mutant AR altering its folding, causing its aggregation into intracellular inclusions, and impairing the autophagic flux. In an in vitro SBMA neuronal model, we previously showed that the antiandrogen bicalutamide and trehalose, a natural disaccharide stimulating autophagy, block ARpolyQ activation, reduce its nuclear translocation and toxicity and facilitate the autophagic degradation of cytoplasmic AR aggregates. Here, in a knock-in SBMA mouse model (KI AR113Q), we show that bicalutamide and trehalose ameliorated SBMA pathology. Bicalutamide reversed the formation of the AR insoluble forms in KI AR113Q muscle, preventing autophagic flux blockage. We demonstrated that apoptosis is activated in KI AR113Q muscle, and that both compounds prevented its activation. We detected a decrease of mtDNA and an increase of OXPHOS enzymes, already at early symptomatic stages; these alterations were reverted by trehalose. Overall, bicalutamide and/or trehalose led to a partial recovery of muscle morphology and function, and improved SBMA mouse motor behavior, inducing an extension of their survival. Thus, bicalutamide and trehalose, by counteracting ARpolyQ toxicity in skeletal muscle, are valuable candidates for future clinical trials in SBMA patients.

Treatment of Early-Stage Gynecological Cancer-Related Lower Limb Lymphedema by Lymphaticovenular Anastomosis-The Triple Incision Approach.

Background and Objectives: Lower extremity lymphedema (LEL) is one of the most relevant chronic and disabling sequelae after gynecological cancer therapy involving pelvic lymphadenectomy (PL). Supermicrosurgical lymphaticovenular anastomosis (LVA) is a safe and effective procedure to treat LEL, particularly indicated in early-stage cases when conservative therapies are insufficient to control the swelling. Usually, preoperative assessment of these patients shows patent and peristaltic lymphatic vessels that can be mapped throughout the limb to plan the sites of skin incision to perform LVA. The aim of this study is to report the efficacy of our approach based on planning LVA in three areas of the lower limb in improving early-stage gynecological cancer-related lymphedema (GCRL) secondary to PL. Materials and Methods: We retrospectively reviewed the data of patients who underwent LVA for the treatment of early-stage GCRL following PL. Patients who had undergone groin dissection were excluded. Our preoperative study based on indocyanine green lymphography (ICG-L) and color doppler ultrasound (CDU) planned three incision sites located in the groin, in the medial surface of the distal third of the thigh, and in the upper half of the leg, to perform LVA. The primary outcome measure was the variation of the mean circumference of the limb after surgery. The changes between preoperative and postoperative limbs' measures were analyzed by Student's t-test. p values < 0.05 were considered significant. Results: Thirty-three patients were included. In every patient, three incision sites were employed to perform LVA. A total of 119 LVA were established, with an average of 3.6 for each patient. The mean circumference of the operated limb showed a significant reduction after surgery, decreasing from 37 cm ± 4.1 cm to 36.1 cm ± 4.4 (p < 0.01). Conclusions: Our results suggest that in patients affected by early-stage GCRL secondary to PL, the placement of incision sites in all the anatomical subunits of the lower limb is one of the key factors in achieving good results after LVA.

Lymphatic Function of the Lower Limb after Groin Dissection for Vulvar Cancer and Reconstruction with Lymphatic SCIP Flap.

Inguinofemoral lymphadenectomy, frequently performed for vulvar cancer, is burdened with substantial immediate and long-term morbidity. One of the most disabling treatment-related sequelae is lower limb lymphedema (LLL). The present study aims to describe the wound complications and the severity of LLL in patients who have undergone groin dissection for vulvar cancer and immediate inguinal reconstruction with the Lymphatic Superficial Circumflex Iliac Perforator flap (L-SCIP). We retrospectively reviewed the data of patients who underwent bilateral groin dissection and unilateral inguinal reconstruction with the L-SCIP. The presence and severity of postoperative LLL during the follow-up period were assessed by lymphoscintigraphy and limbs' volume measurement. In addition, immediate complications at the level of the inguinal area were registered. The changes between preoperative and postoperative limb volumes were analyzed by Student's t test. p values < 0.05 were considered significant. Thirty-one patients were included. The mean variation of volume was 479 ± 330 cc3 in the side where groin reconstruction had been performed, and 683 ± 425 cc3 in the contralateral side, showing smaller variation in the treated side (p = 0.022). Lymphoscintigraphy confirmed the clinical findings. Based on our results, inguinal reconstruction with L-SCIP performed at the same time of groin dissection in patients treated for vulvar cancer can provide a significant protective effect on LLL.

Feasibility, indications and complications of SCIP flap for reconstruction after extirpative surgery for vulvar cancer.

INTRODUCTION: Surgical therapy for vulvar cancer involves wide defects that often require flap-based reconstruction. The goal of the reconstruction is fast wound healing with low donor site morbidity. MATERIALS AND METHODS: This is a retrospective observational cohort study in which we reviewed all patients who underwent surgery for vulvar cancer followed by reconstruction using the Superficial Circumflex Iliac Artery Perforator (SCIP) flap between 2015 and 2020. The primary outcome measure of this investigation was the incidence of wound complications. The secondary outcomes were the surgical indications in terms of establishing the anatomical subunits involved in the resection that made us choose this flap for reconstruction. This study adheres to the STROBE guidelines. RESULTS: Thirty-two patients were included; in two cases, the flap was performed bilaterally for a total of 34 SCIP flaps. The mean age of patients was 70.6 ± 8.6 years, and the mean BMI was 26.8 ± 4.7. The SCIP flap was always feasible. The mean flap size was 128.8 ± 74.3cm2. Three patients showed wound complications. In every patient, the defect involved the vulva, perineum and inguinal area; in 18 patients, the mons pubis was also involved. The mean follow-up was 30 months. During the follow-up, six patients died, and four showed local or nodal cancer relapse. CONCLUSION: Our results suggest that the advantages of SCIP flap for the reconstruction of vulvoperineal defects secondary to vulvar cancer surgery include low complication rate, minimal donor site morbidity, quick dissection, proximity of donor and recipient sites, possibility to harvest large skin islands of variable thickness and chimeric flaps.

The Radiotherapy Role in the Multidisciplinary Management of Locally Advanced Vulvar Cancer: A Multidisciplinary VulCan Team Review.

Locally advanced vulvar cancer (LAVC) is a challenging disease, requiring multidisciplinary management. The aim of this review is to propose an integrated clinical approach including radiotherapy (RT) in the multidisciplinary management of LAVC to customize the treatment. A review of the literature was conducted on PubMed, Scopus, and Cochrane library to acquire all relevant studies on RT in LAVC. Based on the available evidence, RT, with or without concurrent chemotherapy, has a relevant role as adjuvant and exclusive treatment or in the neoadjuvant setting. However, multicentric prospective trials are needed to define the best treatment options based on tumor and patient characteristics. A multidisciplinary and multidimensional assessment can also be useful to identify the most suitable approach, considering patients' age and comorbidities, in view of a better treatment personalization.

Mitochondrial Dysfunctions: A Red Thread across Neurodegenerative Diseases.

Mitochondria play a central role in a plethora of processes related to the maintenance of cellular homeostasis and genomic integrity. They contribute to preserving the optimal functioning of cells and protecting them from potential DNA damage which could result in mutations and disease. However, perturbations of the system due to senescence or environmental factors induce alterations of the physiological balance and lead to the impairment of mitochondrial functions. After the description of the crucial roles of mitochondria for cell survival and activity, the core of this review focuses on the "mitochondrial switch" which occurs at the onset of neuronal degeneration. We dissect the pathways related to mitochondrial dysfunctions which are shared among the most frequent or disabling neurodegenerative diseases such as Alzheimer's, Parkinson's, and Huntington's, Amyotrophic Lateral Sclerosis, and Spinal Muscular Atrophy. Can mitochondrial dysfunctions (affecting their morphology and activities) represent the early event eliciting the shift towards pathological neurobiological processes? Can mitochondria represent a common target against neurodegeneration? We also review here the drugs that target mitochondria in neurodegenerative diseases.