Soft tissue reconstruction of the trunk with pedicled perforator and musculocutaneous flaps: A single-center comparative retrospective study.

BACKGROUND: Soft tissue trunk reconstruction is often challenging. Although free microvascular flaps are a feasible option in case of extensive defects involving deep structures, pedicled flaps represent a good alternative, especially if harvested and dissected with a "microsurgical" approach. The aim of this study is to evaluate the feasibility of trunk reconstruction with the use of pedicled flaps, according to the application of our reconstructive algorithm, and to compare it to other reconstructive methods. PATIENTS AND METHODS: From January 2017 to December 2021, we retrospectively analyzed patients who underwent soft tissue reconstruction of the trunk with pedicled flaps at the authors' institution. Patient's demographic, clinical and surgical characteristics and postoperative complications were recorded and analyzed by descriptive statistics. A comparative analysis was made between the study group and two other groups who underwent reconstruction of trunk defects with free flaps and skin grafts, respectively, at the authors' institution. RESULTS: Forty-seven patients were included in the study. Patients' age ranged between 36 and 82 years (mean: 57.8 years). Twenty-eight patients were male, while 19 patients were female. In 76.6% of patients (36 out of 47), reconstructive procedures were performed to repair defects resulting from cancer resection. Reconstruction of superficial defects was always achieved with perforator flaps (n = 25). In case of full-thickness defects, reconstruction was carried out with musculocutaneous flaps (n = 22); latissimus dorsi and vastus lateralis were the most used flaps for chest and abdominal wall reconstruction, respectively. In our series, we observed only one case of total flap loss requiring re-operation under general anesthesia. Minor complications occurred in 8.5% of cases (4 out of 47 patients). We observed two cases of partial flap necrosis and two cases of wound dehiscence. In the skin grafts group (n = 53), the mean age was 54.5 years (range 39-85) and 56% of patients were male (n = 30). In 66% of cases (n = 30) the defect resulted from oncological resection. The overall complication rate was 18.8% (n = 10). In the free flaps group (n = 10), the mean age was 49.0 years (range 29-77) and 60% of patients (n = 6) were male. In 70% of cases (n = 7) the defect was caused by oncological resection. Complications occurred in two patients (20%). No statistically significant differences were found in terms of overall complication rate between the study group and the two comparative groups (p = .48). A significant correlation was found between the reconstructive method and the type and size of the defect, with reconstruction through free flaps being associated with larger (344.0 vs. 220.4 cm2 ) (p = .04) and full-thickness defects (80.0% vs. 46.8%) (p < .01) if compared to pedicled flaps. CONCLUSIONS: In the new era of microsurgery, pedicled flaps represent a valid alternative to free flaps for the majority of soft tissue defects of the trunk. In our series, no statistically significant differences in terms of complications were found between reconstructions of similar defects achieved with pedicled and free flaps, and free flap use was limited to extensive full-thickness defects. In addition, the rate of postoperative complications with pedicled flaps found in our cohort was lower than the rate reported in the literature.

Latissimus Dorsi Flap and Thoracodorsal Artery Perforator Flap with Immediate Fat Transfer (LIFT and TIFT): A Retrospective Study about Total Breast Reconstruction in High-Risk Patients.

INTRODUCTION: Microsurgical breast reconstruction has become popular over the past twenty years and allows a tailor-tuck approach to each patient. However, smoking or coagulation disorders may switch surgeon's choice towards alternative options. When facing these risk factors, we performed pedicled latissimus dorsi (LD) flap and thoracodorsal artery perforator (TDAP) flap reconstruction with immediate fat transfer (LIFT and TIFT), achieving satisfactory surgical outcomes. Hence, we aim to present our seven-years case-series and discuss our decisional algorithm. MATERIALS AND METHODS: Thirty smoker women and seven women affected by coagulation disorder (n = 37) respectively had LIFT and TIFT surgery and were retrospectively evaluated. Patients' demographics and outcomes were recorded and compared. RESULTS: LIFT patients received higher volumes of immediate fat grafting compared to TIFT patients (p < 0.05), which required additional lipofilling to provide adequate volume amount, since the TDAP flap was not immediately grafted. However, the additional lipofilling procedures and fat volume were similar (p > 0.05). Flap survival reached 100%, and flap necrosis or loss did not occur. Few minor complications were evidenced in the LIFT group only (p > 0.05). CONCLUSION: Based on our experience, we support the reliability of pedicled LD and TDAP flaps with immediate fat transfer in breast reconstruction as valuable alternative to microsurgery in smokers (LIFT) and patients with coagulation disorders (TIFT). However, the results of our study are not conclusive since still must be clarified the role of the smoking and coagulation disorders in microsurgery and the real benefit of a non-microsurgical procedure. LEVEL OF EVIDENCE IV: Opinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert committees. 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 .

Systematic review on spheroids from adipose-derived stem cells: Spontaneous or artefact state?

Three-dimensional (3D) cell cultures represent the spontaneous state of stem cells with specific gene and protein molecular expression that are more alike the in vivo condition. In vitro two-dimensional (2D) cell adhesion cultures are still commonly employed for various cellular studies such as movement, proliferation and differentiation phenomena; this procedure is standardized and amply used in laboratories, however their representing the original tissue has recently been subject to questioning. Cell cultures in 2D require a support/substrate (flasks, multiwells, etc.) and use of fetal bovine serum as an adjuvant that stimulates adhesion that most likely leads to cellular aging. A 3D environment stimulates cells to grow in suspended aggregates that are defined as "spheroids." In particular, adipose stem cells (ASCs) are traditionally observed in adhesion conditions, but a recent and vast literature offers many strategies that obtain 3D cell spheroids. These cells seem to possess a greater ability in maintaining their stemness and differentiate towards all mesenchymal lineages, as demonstrated in in vitro and in vivo studies compared to adhesion cultures. To date, standardized procedures that form ASC spheroids have not yet been established. This systematic review carries out an in-depth analysis of the 76 articles produced over the past 10 years and discusses the similarities and differences in materials, techniques, and purposes to standardize the methods aimed at obtaining ASC spheroids as already described for 2D cultures.

The role of sentinel node tumor burden in modeling the prognosis of melanoma patients with positive sentinel node biopsy: an Italian melanoma intergroup study (N = 2,086).

BACKGROUND: The management of melanoma patients with metastatic melanoma in the sentinel nodes (SN) is evolving based on the results of trials questioning the impact of completion lymph node dissection (CLND) and demonstrating the efficacy of new adjuvant treatments. In this landscape, new prognostic tools for fine risk stratification are eagerly sought to optimize the therapeutic path of these patients. METHODS: A retrospective cohort of 2,086 patients treated with CLND after a positive SN biopsy in thirteen Italian Melanoma Centers was reviewed. Overall survival (OS) was the outcome of interest; included independent variables were the following: age, gender, primary melanoma site, Breslow thickness, ulceration, sentinel node tumor burden (SNTB), number of positive SN, non-sentinel lymph nodes (NSN) status. Univariate and multivariate survival analyses were performed using the Cox proportional hazard regression model. RESULTS: The 3-year, 5-year and 10-year OS rates were 79%, 70% and 54%, respectively. At univariate analysis, all variables, except for primary melanoma body site, were found to be statistically significant prognostic factors. Multivariate Cox regression analysis indicated that older age (P < 0.0001), male gender (P = 0.04), increasing Breslow thickness (P < 0.0001), presence of ulceration (P = 0.004), SNTB size (P < 0.0001) and metastatic NSN (P < 0.0001) were independent negative predictors of OS. CONCLUSION: The above results were utilized to build a nomogram in order to ease the practical implementation of our prognostic model, which might improve treatment personalization.

Diagnostic and prognostic value of magnetic resonance imaging in the detection of tumor depth of invasion and bone invasion in patients with oral cavity cancer.

PURPOSE: To evaluate the accuracy of preoperative contrast-enhanced magnetic resonance imaging (MRI) in the assessment of radiological depth of invasion (rDOI) and bone invasion in patients with oral cavity cancer, and the prognostic value of preoperative rDOI. MATERIALS AND METHODS: This retrospective study included patients with surgically resected oral cavity cancer and preoperative MRI acquired within four weeks before surgery. Two readers evaluated the MRI to assess the superficial and deep bone invasion, preoperative T stage, and measured the rDOI. The rDOI was compared to the histopathological DOI (pDOI), used as reference standard. Prognostic value of preoperative features for the disease-specific survival was evaluated using the Kaplan-Meier curve and multivariable Cox proportional hazards analysis. RESULTS: The final population included 80 patients (50 males, mean age 67.7 ± 13.6 years). There was a strong statistically significant correlation between the rDOI (median 10 mm) and the pDOI (median 9 mm) (ρ: 0.978, p < 0.001). The agreement between MRI and histopathological T stage was excellent (k = 0.93, 95% CI 0.86, 0.99). The sensitivity and specificity of preoperative MRI were 93.3% and 98.8% for deep bone invasion, while they were 75.0% and 95.8% for superficial bone invasion, respectively. The rDOI > 10 mm was associated with poorer disease-specific survival (log-rank p = 0.016). The rDOI remained the only independent preoperative predictor associated with poorer disease-specific survival at multivariable analysis (hazard ratio 5.5; 95% CI 1.14, 26.58; p = 0.033). CONCLUSION: Preoperative MRI is accurate for the assessment of DOI and bone invasion. The rDOI is an independent preoperative predictor of disease-specific survival in patients with oral cavity cancer.

Human Spheroids from Adipose-Derived Stem Cells Induce Calvarial Bone Production in a Xenogeneic Rabbit Model.

ABSTRACT: Calvarial defects can result from several causes. Tissue engineering hold the potential to restore native form and protective function. We have recently shown that stemness and differentiation ability of spheroids from adipose-derived stem cells (S-ASCs) promotes osteoblasts growth within Integra in a small vertebral lesion. In our study, we aimed to test osteogenic potential of S-ASCs in aiding regeneration of a calvarial defect. Groups containing Integra showed increased bone regeneration at the calvarial defect-Integra interface compared with the control group. In particular, S-ASC-derived osteoblasts group showed a superior calvarial remodeling than undifferentiated S-ASCs group. Clusters of ossification were observed in these both groups with enhanced microvasculature density and fibrosis. In conclusion, seeding of S-ASCs in dermal regeneration templates enhanced bone healing in a rabbit calvarial defect model. These findings could prompt the elective use of S-ASCs with enhanced multilineage differentiation potential for tissue engineering purposes.

IgA pemphigus: A systematic review.

BACKGROUND: The clinical, histologic, and immunopathologic features of IgA pemphigus have not been studied on a large scale. OBJECTIVE: To synthesize existing data on the epidemiologic, clinical, histologic, and immunologic features of IgA pemphigus. METHODS: We performed a systematic review using MEDLINE, Embase, and Web of Science databases. Case reports and series of patients with IgA pemphigus were included. RESULTS: A total of 119 eligible studies, comprising 137 patients with IgA pemphigus with a mean age of 51.5 ± 21.0 years, were included. Most patients presented with vesicles (80.8%), pustules (75.0%), and circinate plaques (63.6%). Pruritus was present in 65.6% of reported patients. Intercellular deposition of IgA was noted in almost all patients (97.0%), and the remaining 3.0% of patients had IgA positivity on indirect immunofluorescence or enzyme-linked immunosorbent assay confirming the diagnosis. IgA circulating intercellular antibodies were detected in only 66.7% patients. IgA gammopathy and ulcerative colitis were associated with IgA pemphigus in 9.5% and 6.6% patients, respectively. Oral dapsone and corticosteroids were the mostly commonly used treatments. LIMITATIONS: Results are mainly based on case reports and small case series. CONCLUSIONS: The diagnosis of IgA pemphigus may be considered in patients presenting with vesiculopustular eruption and circinate plaques with truncal and extremity involvement.

Case report: absence of the right piriformis muscle in a woman.

We report a very rare case of a unilaterally absent piriformis muscle in a 60 year old woman. Accompanying variations comprised a common gluteal artery (instead of two distinct superior and inferior gluteal arteries), and an absent gemellus inferior muscle. The contralateral left side showed a normally developed piriformis muscle. In hominoids, the piriformis is constant, but is regularly missing in several other vertebrates. The piriformis muscle is an anatomical landmark for ultrasound investigations and ultrasound-guided interventions in the deep gluteal region such as a superior gluteal nerve block or even a sacral plexus block, also for any surgical approach such as total hip arthroplasty. A missing piriformis muscle therefore affects the orientation in the deep gluteal region and therefore the identification of the targeted structures.

Spheroids from adipose-derived stem cells exhibit an miRNA profile of highly undifferentiated cells.

Two-dimensional (2D) cell cultures have been extensively used to investigate stem cell biology, but new insights show that the 2D model may not properly represent the potential of the tissue of origin. Conversely, three-dimensional cultures exhibit protein expression patterns and intercellular junctions that are more representative of their in vivo condition. Multiclonal cells that grow in suspension are defined as "spheroids," and we have previously demonstrated that spheroids from adipose-derived stem cells (S-ASCs) displayed enhanced regenerative capability. With the current study, we further characterized S-ASCs to further understand the molecular mechanisms underlying their stemness properties. Recent studies have shown that microRNAs (miRNAs) are involved in many cellular mechanisms, including stemness maintenance and proliferation, and adipose stem cell differentiation. Most studies have been conducted to identify a specific miRNA profile on adherent adipose stem cells, although little is still known about S-ASCs. In this study, we investigate for the first time the miRNA expression pattern in S-ASCs compared to that of ASCs, demonstrating that cell lines cultured in suspension show a typical miRNA expression profile that is closer to the one reported in induced pluripotent stem cells. Moreover, we have analyzed miRNAs that are specifically involved in two distinct moments of each differentiation, namely early and late stages of osteogenic, adipogenic, and chondrogenic lineages during long-term in vitro culture. The data reported in the current study suggest that S-ASCs have superior stemness features than the ASCs and they represent the true upstream stem cell fraction present in adipose tissue, relegating their adherent counterparts.

Prediction of Non-sentinel Node Status in Patients with Melanoma and Positive Sentinel Node Biopsy: An Italian Melanoma Intergroup (IMI) Study.

BACKGROUND AND PURPOSE: Approximately 20% of melanoma patients harbor metastases in non-sentinel nodes (NSNs) after a positive sentinel node biopsy (SNB), and recent evidence questions the therapeutic benefit of completion lymph node dissection (CLND). We built a nomogram for prediction of NSN status in melanoma patients with positive SNB. METHODS: Data on anthropometric and clinicopathological features of patients with cutaneous melanoma who underwent CLND after a positive SNB were collected from nine Italian centers. Multivariate logistic regression was utilized to identify predictors of NSN status in a training set, while model efficiency was validated in a validation set. RESULTS: Data were available for 1220 patients treated from 2000 through 2016. In the training set (n = 810), the risk of NSN involvement was higher when (1) the primary melanoma is thicker or (2) sited in the trunk/head and neck; (3) fewer nodes are excised and (4) more nodes are involved; and (5) the lymph node metastasis is larger or (6) is deeply located. The model showed high discrimination (area under the receiver operating characteristic curve 0.74, 95% confidence interval [CI] 0.70-0.79) and calibration (Brier score 0.16, 95% CI 0.15-0.17) performance in the validation set (n = 410). The nomogram including these six clinicopathological variables performed significantly better than five other previously published models in terms of both discrimination and calibration. CONCLUSIONS: Our nomogram could be useful for follow-up personalization in clinical practice, and for patient risk stratification while conducting clinical trials or analyzing their results.

Tuberous Breast: Past, Present, and Future: Personal Classification, Treatment, and Surgical Outcomes.

BACKGROUND: Tuberous breast (TB) is a rare congenital deformity, which may appear in different clinical forms representing various degrees of a single pathological entity. The worst cases are characterized by severe hypoplasia. Following a detailed analysis of the available relevant literature and a significant number of treated cases, in this article, the authors propose a new classification, with the aim of summarizing and simplifying a more intuitive categorization of the malformation, considering all the clinical aspects and including all types of TBs, even the minor ones, thus allowing a more immediate diagnosis and surgical planning. METHODS: Between September 2006 and December 2015, 78 patients with TBs underwent surgical procedures to correct the deformity. The patients' mean age was 18.6 years, ranging between 17 and 26 years. There being 11 monolateral deformities, the treated TBs amounted to 145. A periareolar approach, adipo-glandular flaps, and dual plane breast implant placements were performed. Postoperative follow-up include photos collected 12 months after operation. The authors present a personal classification including all the forms of the deformity, plus the minor forms based on the following 2 principal categories: hypoplastic and normoplastic TBs, taking into account all the clinical aspects of the malformation including the morphology and the consistency of the breast. CONCLUSIONS: Preoperative identification of the type of the deformity is essential to obtain satisfactory results and a complete and intuitive classification including all the possible variants of the deformity, even the minor forms, and fundamental in diagnosing and resolving the problem. In this article, the authors propose a personal classification and surgical procedure to resolve the malformation.

An algorithm to improve outcomes of radial forearm flap donor site.

Abstarct Background: Due to the high rate of donor site complications the Radial Forearm Flap (RFF) has lost ground in favor of the Antero-lateral tight flap (ALT) and other flaps. We have designed a reconstruction algorithm for reconstruction of its donor site. The goal of this study was to retrospectively evaluate the impact of this algorithm on RFF donor site complication rates. METHODS: The authors analyzed retrospectively 31 patients who underwent free radial forearm flap reconstruction between November 2009 and May 2013. Donor site complications were compared with data from patients treated before introdutction of the algorithm. Within the group were compared patients in which the flap was harvested suprafascial with those in which the flap was harvested as subfascial. RESULTS: Before application of the algorithm, there was a 23.3% complication rate at the RFF donor site, in our experience. After introduction of the algorithm, complication rate has dropped to 3.2%, consisting in a partial skin graft necrosis treated by local wound-care and healed without further intervention. CONCLUSIONS: Application of the algorithm described has led to a significant reduction in RFF donor site complication rates. This demonstrates that if flap donor sites are analyzed and tailor treated in the same way as primary defects are, instead of being given secondary importance and just grafted, outcomes improve.

Seeding nerve sutures with minced nerve-graft (MINE-G): a simple method to improve nerve regeneration in rats.

BACKGROUND: The aim of this study was to assess the effect of seeding the distal nerve suture with nerve fragments in rats. METHODS: On 20 rats, a 15 mm sciatic nerve defect was reconstructed with a nerve autograft. In the Study Group (10 rats), a minced 1 mm nerve segment was seeded around the nerve suture. In the Control Group (10 rats), a nerve graft alone was used. At 4 and 12 weeks, a walking track analysis with open field test (WTA), hystomorphometry (number of myelinated fibers (n), fiber density (FD) and fiber area (FA) and soleus and gastrocnemius muscle weight ratios (MWR) were evaluated. The Student t-test was used for statistical analysis. RESULTS: At 4 and 12 weeks the Study Group had a significantly higher n and FD (p = .043 and .033). The SMWR was significantly higher in the Study Group at 12 weeks (p = .0207). CONCLUSIONS: Seeding the distal nerve suture with nerve fragments increases the number of myelinated fibers, the FD and the SMWR. The technique seems promising and deserves further investigation to clarify the mechanisms involved and its functional effects.

Characteristics, Management Techniques, and Outcomes of the Most Common Soft-Tissue Hand Tumors: A Literature Review and Our Experience.

INTRODUCTION: Diagnosis of the hand's soft-tissue tumors is often difficult because of the different anatomic structures present in this region and yet clinicians must be able to distinguish typical benign entities from life-threatening or limb-threatening malignant diseases. MATERIALS AND METHODS: At the Department of Plastic and Reconstructive Surgery at the University of Palermo, 629 patients with hand tumors were studied. Treatment was surgical for all of them; also radiotherapy and chemotherapy were necessary based on the histological diagnosis. CONCLUSIONS: Our retrospective study with a literature review aims to present the most commonly observed soft-tissue hand lesions, analyzing their causes, their objective and instrumental evaluation, and their treatments.

Variability and reliability of the vastus lateralis muscle anatomy.

PURPOSE: The aims of this study are to investigate the variability of the morphological and neurovascular anatomy of the vastus lateralis (VL) muscle and to describe the relationships among its intramuscular partitions and with the other muscles of the quadriceps femoris. Clinical implications in its reliability as a flap donor are also discussed. METHODS: In 2012, the extra- and intramuscular neurovascular anatomy of the VL was investigated in 10 cadaveric lower limbs. In three specimens, the segmental arterial pedicles were injected with latex of different colors to point out their anastomotic connections. The morphological anatomy was investigated with regard to the mutual relationship of the three muscular partitions and the relation of the VL with the other muscles of the quadriceps femoris. RESULTS: The VL has a segmental morphological anatomy. However, the fibers of its three partitions interconnect individually and with the other bellies of the quadriceps femoris, particularly, in several variable portions with the vastus intermedius and mainly in the posterior part of the VL. The lateral circumflex femoral artery and its branches have variable origin, but demonstrate constant segmental distribution. Intramuscular dissection and colored latex injections show a rich anastomotic vascular network among the three partitions. CONCLUSIONS: Moderate variability exists in both the myological and the neurovascular anatomy of the VL. Despite this variability, the anatomy of the VL always has a constant segmental pattern, which makes the VL a reliable flap donor. Detailed knowledge of the VL anatomy could have useful applications in a broad clinical field.

Functional evidence that a recently evolved Drosophila sperm-specific gene boosts sperm competition.

In many species, both morphological and molecular traits related to sex and reproduction evolve faster in males than in females. Ultimately, rapid male evolution relies on the acquisition of genetic variation associated with differential reproductive success. Many newly evolved genes are associated with novel functions that might enhance male fitness. However, functional evidence of the adaptive role of recently originated genes in males is still lacking. The Sperm dynein intermediate chain multigene family, which encodes a Sperm dynein intermediate chain presumably involved in sperm motility, originated from complex genetic rearrangements in the lineage that leads to Drosophila melanogaster within the last 5.4 million years since its split from Drosophila simulans. We deleted all the members of this multigene family resident on the X chromosome of D. melanogaster by chromosome engineering and found that, although the deletion does not result in a reduction of progeny number, it impairs the competence of the sperm in the presence of sperm from wild-type males. Therefore, the Sperm dynein intermediate chain multigene family contributes to the differential reproductive success among males and illustrates precisely how quickly a new gene function can be incorporated into the genetic network of a species.

Prophylactic chimera anterolateral thigh/vastus lateralis flap: preventing complications in high-risk head and neck reconstruction.

PURPOSE: In high-risk head and neck cases treated with tumor resection and associated radical neck dissection, orocutaneous fistulas and wound breakdowns in the neck are relatively frequent and can have serious consequences, such as carotid blowout syndrome (CBS), the need for salvage reoperations, and prolonged recovery time. The authors present the application of a prophylactic chimeric anterolateral thigh (ALT) and vastus lateralis (VL) flap to prevent complications. MATERIALS AND METHODS: A retrospective review was performed of a historical group (96 patients) of patients with head and neck cancer treated with tumor resection, radical neck dissection, and microsurgical reconstruction of the tumor site only and a prospective cohort (21 patients) in which a chimeric ALT-VL flap was used to simultaneously reconstruct the tumor site and sternocleidomastoid muscle to fill dead space and protect the carotid artery. RESULTS: The rate of complications was higher in the historical group: CBS occurred in 4.1% and orocutaneous fistulas in 11.5% of patients; 5.2% of patients required major salvage surgery for a wound complication. In the cohort group, no CBS or orocutaneous fistula occurred and no major salvage surgical procedure was needed. CONCLUSIONS: Prophylactic ALT-VL flaps in high-risk head and neck cancers provide adequate and long-lasting soft tissue coverage for the carotid artery, with minimal additional morbidity, and could be beneficial in preventing serious and life-threatening wound complications and the need for reoperation.