Publications by authors named "Massimo Pinelli"

29 Publications

  • Page 1 of 1

Molecular Mechanisms and Physiological Changes behind Benign Tracheal and Subglottic Stenosis in Adults.

Int J Mol Sci 2022 Feb 22;23(5). Epub 2022 Feb 22.

Respiratory Diseases Unit, Department of Medical and Surgical Sciences, University of Modena Reggio Emilia, University Hospital of Modena, 41121 Modena, Italy.

Laryngotracheal stenosis (LTS) is a complex and heterogeneous disease whose pathogenesis remains unclear. LTS is considered to be the result of aberrant wound-healing process that leads to fibrotic scarring, originating from different aetiology. Although iatrogenic aetiology is the main cause of subglottic or tracheal stenosis, also autoimmune and infectious diseases may be involved in causing LTS. Furthermore, fibrotic obstruction in the anatomic region under the glottis can also be diagnosed without apparent aetiology after a comprehensive workup; in this case, the pathological process is called idiopathic subglottic stenosis (iSGS). So far, the laryngotracheal scar resulting from airway injury due to different diseases was considered as inert tissue requiring surgical removal to restore airway patency. However, this assumption has recently been revised by regarding the tracheal scarring process as a fibroinflammatory event due to immunological alteration, similar to other fibrotic diseases. Recent acquisitions suggest that different factors, such as growth factors, cytokines, altered fibroblast function and genetic susceptibility, can all interact in a complex way leading to aberrant and fibrotic wound healing after an insult that acts as a trigger. However, also physiological derangement due to LTS could play a role in promoting dysregulated response to laryngo-tracheal mucosal injury, through biomechanical stress and mechanotransduction activation. The aim of this narrative review is to present the state-of-the-art knowledge regarding molecular mechanisms, as well as mechanical and physio-pathological features behind LTS.
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http://dx.doi.org/10.3390/ijms23052421DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8910114PMC
February 2022

Microfragmented adipose tissue is associated with improved ex vivo performance linked to HOXB7 and b-FGF expression.

Stem Cell Res Ther 2021 08 28;12(1):481. Epub 2021 Aug 28.

Department of Medical and Surgical Sciences for Children and Adults, University-Hospital of Modena and Reggio Emilia, Modena, Italy.

Introduction: Adipose tissue (AT) has become a source of mesenchymal stromal/stem cells (MSC) for regenerative medicine applications, in particular skeletal disorders. Several enzymatic or mechanical procedures have been proposed to process AT with the aim to isolate cells that can be locally implanted. How AT is processed may impact its properties. Thus, we compared AT processed by centrifugation (C-AT) to microfragmentation (MF-AT). Focusing on MF-AT, we subsequently assessed the impact of synovial fluid (SF) alone on both MF-AT and isolated AT-MSC to better understand their cartilage repair mechanisms.

Materials And Methods: MF-AT and C-AT from the same donors were compared by histology and qRT-PCR immediately after isolation or as ex vivo cultures using a micro-tissue pellet system. The in vitro impact of SF on MF-AT and AT-MSC was assessed by histological staining and molecular analysis.

Results: The main AT histological features (i.e., increased extracellular matrix and cellularity) of the freshly isolated or ex vivo-cultured MF-AT persisted compared to C-AT, which rapidly deteriorated during culture. Based on our previous studies of HOX genes in MSC, we investigated the involvement of Homeobox Protein HOX-B7 (HOXB7) and its target basic Fibroblast Growth Factor (bFGF) in the molecular mechanism underlying the improved performance of MF-AT. Indeed, both these biomarkers were more prominent in freshly isolated MF-AT compared to C-AT. SF alone preserved the AT histological features of MF-AT, together with HOXB7 and bFGF expression. Increased cell performance was also observed in isolated AT-MSC after SF treatment concomitant with enhanced HOXB7 expression, although there was no apparent association with bFGF.

Conclusions: Our findings show that MF has a positive effect on the maintenance of AT histology and may trigger the expression of trophic factors that improve tissue repair by processed AT.
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http://dx.doi.org/10.1186/s13287-021-02540-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8399787PMC
August 2021

Standardization and Selection of High-risk Patients for Surgical Wound Infections in Plastic Surgery.

Plast Reconstr Surg Glob Open 2021 Mar 23;9(3):e3472. Epub 2021 Mar 23.

Division of Plastic and Reconstructive Surgery, University Hospital of Modena, Modena, Italy.

Background: The aim of the present study was to show that the Infection Risk Index (IRI), based on only 3 factors (wound classification, American Society of Anesthesiologists score, and duration of surgery), can be used to standardize selection of infection high-risk patients undergoing different surgical procedures in Plastic Surgery.

Methods: In our Division of Plastic Surgery at Modena University Hospital, we studied 3 groups of patients: Group A (122 post-bariatric abdominoplasties), Group B (223 bilateral reduction mammoplasties), and Group C (201 tissue losses with first intention healing). For each group, we compared surgical site infection (SSI) rate and ratio between patients with 0 or 1 risk factors (IRI score 0 or 1) and patients with 2 or 3 risk factors (IRI score 2 or 3).

Results: In group A, patients with IRI score 0-1 showed an SSI Ratio of 2.97%, whereas patients with IRI score 2-3 developed an SSI ratio of 27.27%. In group B, patients with IRI score 0-1 showed an SSI ratio of 2.99%, whereas patients with IRI score 2-3 developed an SSI ratio of 18.18%. In group C, patients with IRI score 0-1 showed an SSI ratio of 7.62%, whereas patients with IRI score 2-3 developed an SSI ratio of 30.77%.

Conclusions: Existing infection risk calculators are procedure-specific and time-consuming. IRI score is simple, fast, and unspecific but is able to identify patients at high or low risk of postoperative infections. Our results suggest the utility of IRI score in refining the infection risk stratification profile in Plastic Surgery.
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http://dx.doi.org/10.1097/GOX.0000000000003472DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062150PMC
March 2021

Autologous fat grafting in the treatment of a scleroderma stump-skin ulcer: a case report.

Case Reports Plast Surg Hand Surg 2021 Feb 12;8(1):18-22. Epub 2021 Feb 12.

Plastic Surgery Unit, Azienda Ospedaliero-Universitaria, Policlinico di Modena, Modena, Italy.

Here we describe the case of a 60-year-old-woman with systemic sclerosis sent to our Scleroderma Unit to treat digital stumps. The stumps were successfully treated with autologous fat grafting (crown-shape infiltration). Our technique of autologous lipotransfer improved wound healing in a scleroderma patient with stump-digital ulcers where all other options failed.
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http://dx.doi.org/10.1080/23320885.2021.1881521DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7889081PMC
February 2021

Lipofilling after Laser-Assisted Treatment for Facial Filler Complication: Volumetric and Regenerative Effect.

Plast Reconstr Surg 2021 03;147(3):585-591

From the Division of Plastic Surgery, University of Modena and Reggio Emilia.

Background: Nonresorbable substances are still injected to enhance soft-tissue volumes and fill subcutaneous defects. The minimally invasive intralesional laser treatment can remove foreign substances and the inflammatory reaction, eventually leaving depression and scar tissue in the treated area. Fat grafting can restore volume loss and improve scar tissue.

Methods: From March of 2010 to February of 2017, 33 patients were studied. All of them had suffered from inflammatory reactions to permanent facial fillers and had been treated with the 808-nm diode laser at the authors' institution. The evacuation of material had left facial asymmetry and visible depression. To restore facial aesthetic units, fat grafting was performed. The minimum follow-up was 6 months.

Results: Volume restoration was recognized (according to the Global Aesthetic Improvement Scale) as significantly improved in 22 patients, moderately improved in eight patients, and slightly improved in three patients. Improvement in atrophic and scarred tissues (with an apparent thickening of the skin or even elimination of scars) was also assessed with the following results: 25 patients were very much improved and eight were moderately improved.

Conclusions: This is the first study on filler-induced complications of the face treated by intralesional laser treatment followed by lipofilling. A systematic approach to volume restoration is proposed to patients who had filler removal of the face. There was a high degree of patient satisfaction with this technique.

Clinical Question/level Of Evidence: Therapeutic, IV.
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http://dx.doi.org/10.1097/PRS.0000000000007611DOI Listing
March 2021

Extended and unusual indications in jaw reconstruction with the fibula flap: An overview based on our 30-year experience.

Ann Med Surg (Lond) 2021 Feb 5;62:37-42. Epub 2021 Jan 5.

Department of Medical and Surgical Sciences, Division of Plastic Surgery, University of Modena and Reggio Emilia, Policlinico of Modena, Largo Pozzo 71, 41124, Modena, Italy.

Since the introduction of fibula flap as a reconstructive technique, an evolution of indications has been observed. Our first report of a traumatic mandibular reconstruction using fibula flap was in 1992. The vast majority of indications for surgery, are: malignant tumors, benign neoplasms, osteoradionecrosis and traumas. Nevertheless, extended indications have been described such as the treatment of dentoalveolar defect without bone discontinuity or reconstruction of maxilla defect up to type III (A and B), according to Cordeiro's classification. Unusual indications include cleft palate malformations with bone discontinuity less than 6 cm. Moreover, a particular attention should be focus on fibula flap harvest with more innovative technologies than traditional use of monopolar or bipolar and their advantages in pre and postoperative management.
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http://dx.doi.org/10.1016/j.amsu.2020.12.049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806501PMC
February 2021

Tip of the Tongue Reconstruction with Prelaminated Fasciomucosal Radial Forearm Free Flap.

Plast Reconstr Surg Glob Open 2020 Dec 2;8(12):e3226. Epub 2020 Dec 2.

Department of Otorhinolaryngology Head and Neck Surgery, University Hospital of Modena, Largo del Pozzo, 71, Modena, Italy.

Tongue cancer is the most common malignant neoplasm of the oral cavity. Occurrence in the tip of the tongue (TOT) is rare. We describe a case report of a TOT tumor excision and reconstruction with a prelaminated fasciomucosal radial forearm free flap. A 41-year-old white man was referred to our department for a squamous cell carcinoma of the tip of the tongue. The patient worked as an air traffic control official; therefore, conservation of speech intelligibility, both in Italian and English language, was of paramount importance. A transoral excision of TOT, bilateral selective neck dissection, and reconstruction with prelaminated fasciomucosal radial forearm free flap were performed. Adjuvant radiotherapy was necessary. The patient was completely re-established as an air traffic control officer. Successful tongue reconstruction of smaller defects depends on thinness, pliability of flap, and conservation of tongue mobility. Surgical options for TOT reconstruction are facial artery muscolomucosa flap, Zhao flap, radial forearm free flap, or primary suture. In the authors' opinion, a fasciomucosal prelaminated RFFF offers a series of advantages for TOT reconstruction. The absence of subcutaneous tissue makes the PFRFFF much thinner than fascio-cutaneous flaps. Compared with mucosal loco-regional flaps, prelaminated flaps allow the preservation of oral mucosa lining while providing adequate bulk and reduced scar formation for optimal func- tional recovery. In our case report, the fasciomucosal flap allowed an adequate reconstruction of TOT volume with good functional and aesthetic outcomes. The flap's added bulk and its minimal scar retraction granted free tongue movement and optimal speech intelligibility.
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http://dx.doi.org/10.1097/GOX.0000000000003226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787281PMC
December 2020

Factors related to delayed treatment: A case report of a huge cutaneous horn and review of the literature.

Ann Med Surg (Lond) 2020 Dec 10;60:384-388. Epub 2020 Nov 10.

Department of Medical and Surgical Sciences, Division of Plastic Surgery, University of Modena and Reggio Emilia, Policlinico of Modena, Largo Pozzo 71, 41124, Modena, Italy.

We present a case of a man with a giant cutaneous horn over his frontal region. This case has been presented for the size of the lesion, due to delayed treatment, and to illustrate the reasons why the growth of this lesion has been possible in a western country, in the 21st century. It was a solitary, not painful lesion which caused significant aesthetic problems. The diagnosis was based on an ultrasonographic study and the treatment of choice was a surgical excision. This case is an opportunity to review the literature about the cutaneous horns, to talk about the main causes of delayed diagnosis and treatment of cutaneous lesions and, to define the role of the specialist in the assessment of emotions and patient support.
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http://dx.doi.org/10.1016/j.amsu.2020.11.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7670244PMC
December 2020

The Use of Cold Atmospheric Plasma Device in Flap Elevation.

Plast Reconstr Surg Glob Open 2020 May 22;8(5):e2815. Epub 2020 May 22.

Department of Medical and Surgical Sciences, Division of Plastic Surgery, University of Modena and Reggio Emilia, Modena, Italy.

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http://dx.doi.org/10.1097/GOX.0000000000002815DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7572129PMC
May 2020

Arming Mesenchymal Stromal/Stem Cells Against Cancer: Has the Time Come?

Front Pharmacol 2020 29;11:529921. Epub 2020 Sep 29.

Laboratory of Cellular Therapy, Division of Oncology, Department of Medical and Surgical Sciences for Children & Adults, University-Hospital of Modena and Reggio Emilia, Modena, Italy.

Since mesenchymal stromal/stem cells (MSCs) were discovered, researchers have been drawn to study their peculiar biological features, including their immune privileged status and their capacity to selectively migrate into inflammatory areas, including tumors. These properties make MSCs promising cellular vehicles for the delivery of therapeutic molecules in the clinical setting. In recent decades, the engineering of MSCs into biological vehicles carrying anticancer compounds has been achieved in different ways, including the loading of MSCs with chemotherapeutics or drug functionalized nanoparticles (NPs), genetic modifications to force the production of anticancer proteins, and the use of oncolytic viruses. Recently, it has been demonstrated that wild-type and engineered MSCs can release extracellular vesicles (EVs) that contain therapeutic agents. Despite the enthusiasm for MSCs as cyto-pharmaceutical agents, many challenges, including controlling the fate of MSCs after administration, must still be considered. Preclinical results demonstrated that MSCs accumulate in lung, liver, and spleen, which could prevent their engraftment into tumor sites. For this reason, physical, physiological, and biological methods have been implemented to increase MSC concentration in the target tumors. Currently, there are more than 900 registered clinical trials using MSCs. Only a small fraction of these are investigating MSC-based therapies for cancer, but the number of these clinical trials is expected to increase as technology and our understanding of MSCs improve. This review will summarize MSC-based antitumor therapies to generate an increasing awareness of their potential and limits to accelerate their clinical translation.
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http://dx.doi.org/10.3389/fphar.2020.529921DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7553050PMC
September 2020

Genetic Engineering as a Strategy to Improve the Therapeutic Efficacy of Mesenchymal Stem/Stromal Cells in Regenerative Medicine.

Front Cell Dev Biol 2020 21;8:737. Epub 2020 Aug 21.

Gonçalo Moniz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Salvador, Brazil.

Mesenchymal stem/stromal cells (MSCs) have been widely studied in the field of regenerative medicine for applications in the treatment of several disease settings. The therapeutic potential of MSCs has been evaluated in studies and , especially based on their anti-inflammatory and pro-regenerative action, through the secretion of soluble mediators. In many cases, however, insufficient engraftment and limited beneficial effects of MSCs indicate the need of approaches to enhance their survival, migration and therapeutic potential. Genetic engineering emerges as a means to induce the expression of different proteins and soluble factors with a wide range of applications, such as growth factors, cytokines, chemokines, transcription factors, enzymes and microRNAs. Distinct strategies have been applied to induce genetic modifications with the goal to enhance the potential of MCSs. This review aims to contribute to the update of the different genetically engineered tools employed for MSCs modification, as well as the factors investigated in different fields in which genetically engineered MSCs have been tested.
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http://dx.doi.org/10.3389/fcell.2020.00737DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7471932PMC
August 2020

Setting of helium plasma device (J-Plasma) in flap elevation.

J Vasc Surg Cases Innov Tech 2020 Sep 15;6(3):446. Epub 2020 Jul 15.

Department of Plastic and Reconstructive Surgery, University Hospital of Modena, Modena, Italy.

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http://dx.doi.org/10.1016/j.jvscit.2020.07.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7451687PMC
September 2020

Diagnosis and treatment of upper eyelid lipoma: A case report.

Am J Ophthalmol Case Rep 2020 Dec 18;20:100874. Epub 2020 Aug 18.

University of Modena and Reggio Emilia, Department of Surgical Sciences, Division of Plastic Surgery, Largo Pozzo 71, 41124, Modena, Italy.

Purpose: Presentation of a rare lesion: a case of upper eyelid lipoma.

Observations: A 76-year-old otherwise healthy woman presented with a right upper eyelid swelling. Her medical history was recorded. On ophthalmologic examination a soft, non-ulcerated and not well-circumscribed mass was evident. An ultrasonography examination was carried out showing a hyperechoic non capsulated mass situated between the superior orbital margin and the orbicularis oculi muscle.

Conclusions And Importance: Eyelid lipomas must be differentiated from herniated orbital fat, cystic lesions, tumours, and the lacrimal gland.A pre-operative differential diagnosis of eyelid lipoma can be done through medical history, ophthalmologic, and ultrasonography examinations. Nevertheless, in case of doubt a magnetic resonance imaging (MRI) should be performed to assess a possible orbital involvement and to plan for the right surgical procedure to be performed.
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http://dx.doi.org/10.1016/j.ajoc.2020.100874DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7452129PMC
December 2020

Tattooing of the nipple-areola complex: What not to do. A case series.

Ann Med Surg (Lond) 2020 Jul 30;55:305-307. Epub 2020 May 30.

Department of Medical and Surgical Sciences, Division of Plastic Surgery, University of Modena and Reggio Emilia, Largo Pozzo 71, 41124, Modena, Italy.

Introduction: Reconstruction of the nipple areola complex (NAC) is the final and easier step of breast reconstruction. However, surgeons, especially if trainees, typically have not developed tattoo skills during their training. The aim of this report is to share advice developed in our clinical practice that would minimize patient complaints and complications while performing NAC tattoos.

Methods: From January 2016 to May 2018, reconstruction of NAC was performed in 48 consecutive patients. Nipple reconstruction was performed initially using skin flaps and this was followed three to eight months later by NAC tattooing. We analyzed medical reports at 12 months follow-up where we usually record patient satisfaction (very satisfied, satisfied, dissatisfied) and every patient's complaint or complication.

Results: Thirty-two patients (67%) were very satisfied of NAC tattooing, twelve patients (25%) satisfied, while four patients (8%) dissatisfied. Patients complained for not having involved in choosing color, areas without sufficient pigment, extreme darkness of the tattooed NAC and artificial look.

Conclusion: Tattooing is a simple and safe procedure, with a high satisfaction rate. Based on our experience, despite some technical aspects have to be considered, it is a procedure that can be safely performed by plastic surgical trainees.
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http://dx.doi.org/10.1016/j.amsu.2020.05.041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7287191PMC
July 2020

Overall survival in patients with lung adenocarcinoma harboring "niche" mutations: an observational study.

Oncotarget 2020 Feb 4;11(5):550-559. Epub 2020 Feb 4.

Institute of Pathology, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy.

In addition to the most common somatic lung cancer mutations (i. e., KRAS and EGFR mutations), other genes may harbor mutations that could be relevant for lung cancer. We defined BRAF, c-MET, DDR2, HER2, MAP2K1, NRAS, PIK3CA, and RET mutations as "niche" mutations and analyzed. The aim of this retrospective cohort study was to assess the differences in the overall survival (OS) of patients with lung adenocarcinoma harboring niche somatic mutations. Data were gathered for 252 patients. Mutations were observed in all genes studied, except c-MET, DDR2, MAP2K1, and RET. The multivariable analysis showed that 1) niche mutations had a higher mortality than EGFR mutations (HR = 2.3; 95% CI = 1.2-4.4; = 0.009); 2) KRAS mutations had a higher mortality than EGFR mutations (HR = 2.5; 95% CI = 1.4-4.5; = 0.003); 3) niche mutations presented a similar mortality to KRAS mutations (HR = 0.9; 95% CI = 0.6-1.5; = 0.797). Three cohorts of mutations were selected from patients with lung adenocarcinoma and their OS was compared. Mutations that were searched for, were 1) BRAF, c-MET, DDR2, HER2, MAP2K1, NRAS, PIK3CA, and RET; 2) K-RAS; and 3) EGFR. Differences in OS between these three cohorts were assessed by means of a multivariable Cox model that adjusted for age, sex, smoking habits, clinical stages, and treatments. Niche mutations exhibited an increased risk of death when compared with EGFR mutations and a similar risk of death when compared with KRAS mutations.
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http://dx.doi.org/10.18632/oncotarget.27472DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7007296PMC
February 2020

Fibula Free Flap Elevation without Tourniquet: Are Harmonic Scalpel Shears Useful?

Plast Reconstr Surg Glob Open 2019 Sep 10;7(9):e2409. Epub 2019 Sep 10.

Division of Plastic Surgery, University of Modena and Reggio Emilia, Largo Pozzo 71, 41124 Modena, Italy.

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http://dx.doi.org/10.1097/GOX.0000000000002409DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6908411PMC
September 2019

Dermal Matrix Fixation: A Good Adhesion to Wound Edges without Vascularization Impairment.

Plast Reconstr Surg Glob Open 2019 Jul 24;7(7):e2327. Epub 2019 Jul 24.

Division of Plastic Surgery, University of Modena and Reggio Emilia, Modena, Italy.

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http://dx.doi.org/10.1097/GOX.0000000000002327DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6952155PMC
July 2019

A Rare Case of Nipple-Areolar Complex Partial Necrosis following Micropigmentation: What to Learn?

Plast Reconstr Surg Glob Open 2019 Nov 27;7(11):e2494. Epub 2019 Nov 27.

Division of Plastic Surgery, University of Modena and Reggio Emilia, Modena, Italy.

A 52-year-old woman, without any comorbidity, presented at our institution for reconstruction of nipple-areolar complex (NAC). Nipple reconstruction was obtained through local skin flaps. After 2 months, a tattoo of the NAC was performed. Follow-up was planned at 6 months. Nevertheless, the patient came to our attention 2 days after tattooing for partial necrosis of the epidermal-dermal layer of the tattooed area with partial muscular layer exposition. Empirical antibiotic treatment was immediately started to avoid infection. Daily medications were performed for 3 weeks. Complete healing was obtained within 3 weeks without the necessity of a skin graft. We think that the partial necrosis of the NAC occured because of vascular impairment of the dermal and subdermal vascular plexus during micropigmentation. From this experience, we developed some advice to improve our clinical practice by allowing surgeons, especially if trainees, to avoid complications in performing NAC micropigmentation.
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http://dx.doi.org/10.1097/GOX.0000000000002494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6908356PMC
November 2019

Correlating tumor-infiltrating lymphocytes and lung cancer stem cells: a cross-sectional study.

Ann Transl Med 2019 Nov;7(22):619

Division of Thoracic Surgery, Department of Medical and Surgical Sciences for Children & Adults, University of Modena and Reggio Emilia, Modena, Italy.

Background: Lung cancer stem cells (LCSCs) are endowed with high aldehyde dehydrogenase (ALDH) expression and play roles in tumor proliferation, metastasis, and drug resistance. Their elusive nature may allow them to escape the immune response by tumor-infiltrating lymphocytes (TILs), which can positively affect the outcome in non-small cell lung cancer (NSCLC) patients. Despite independent investigations on both LCSCs and TILs, the relationship between the two has been very marginally considered. We analyzed whether these two cell types may be related as a prerequisite for novel diagnostic and therapeutic approaches.

Methods: In this cross-sectional study, NSCLC human surgical specimens from 12 patients were tested by ALDEFLUOR assay to identify ALDH cells. Fluorescence-activated cell sorting (FACS) analyses for CD3+, CD4+, and CD8+ TILs were performed in combination with immunohistochemistry evaluation.

Results: Statistically positive correlations were found between ALDH+ and CD8+, and between ALDH+ and CD3+ cells populations; no correlation was found between ALDH+ and CD4+ cells. The expression of CD3+ and CD8+ by cells accounted for 40.1% and 58.7%, respectively, of the variability of ALDH+ cell expression by an R-squared index, which highlights the strong correlation between TILs and LCSCs. Immunohistochemistry revealed 6-25% positive cells.

Conclusions: We report a correlation between cytotoxic TILs and LCSCs, which may contribute to the future development of targeted therapies focusing on the different roles of lymphocytes against lung cancer.
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http://dx.doi.org/10.21037/atm.2019.11.27DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6944548PMC
November 2019

Objective Selection Criteria between ALT and Radial Forearm Flap in Oral Soft Tissues Reconstruction.

Indian J Plast Surg 2019 May 30;52(2):166-170. Epub 2019 Jul 30.

Department of Plastic and Reconstructive Surgery, Policlinico di Modena, University of Modena and Reggio Emilia, Modena, Italia.

Different locoregional and free flaps were described for oral soft tissues reconstruction after oncological resections; however, free flaps remain the first choice. Among free flaps, the radial forearm flap (RFF) and the anterolateral thigh perforator flap (ALT) are preferred the most. The lack of standardization of the flap choice leaves the selection to the surgeon's experience. The purpose of our observational study is to provide an algorithm to support the flap choice for the reconstruction of oral soft tissues. Sixty patients with squamous cell carcinoma of oral soft tissues were enrolled in our study. All the patients underwent preoperative magnetic resonance imaging (MRI) to measure the three-dimensional size of the tumor. During the follow-up, the patients were evaluated by using the University of Washington-Quality of Life Questionnaire. The questionnaire score was better for small tumors and worse for large tumors in both functional and relational fields. We observed that most of the overlapping results were obtained for small defects and the choice of RFF, as well as for large defects and the use of ALT. We observed that in the preoperative time, it is possible to select which flap between radial forearm and ALT is more appropriate for oral soft tissues defects reconstruction, according to the size of the tumor evaluated by MRI. We propose a decisional algorithm that suggests the type of flap to use between ALT and RFF.
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http://dx.doi.org/10.1055/s-0039-1693504DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6785316PMC
May 2019

Can surgery relieve pain and act as first-line treatment for a large metastasis of the sternum?

Int J Surg Case Rep 2019 24;63:125-128. Epub 2019 Sep 24.

Division of Thoracic Surgery, Department of Medical and Surgical Sciences for Children & Adults, University of Modena and Reggio Emilia, Modena, Italy. Electronic address:

Background: There are few papers published on sternal metastasis from renal cell carcinoma. The unifying element is the operability of the sternal metastasis if it is the only site of metastasis, on the operability of the primary site of the tumor and on the patient's health conditions.

Presentation Of The Case: We present a case of a 66-years-old man undergone sternal resection for a large painful metastasis. He was previously undergone left nephrectomy for clear cells carcinoma. En bloc resection of the sternal manubrium and right clavicle was performed, a Gore-Tex mesh was placed. Histology confirmed metastasis of kidney clear cells carcinoma. Patient was discharged with no complications and no pain. Chest CT at six months follow up was negative for recurrence.

Discussion And Conclusion: We highlighted the importance of surgery as possible first-line treatment in symptomatic large sternum metastasis. Therefore, prospective studies should be considered to confirm our strategy.
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http://dx.doi.org/10.1016/j.ijscr.2019.09.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6796717PMC
September 2019

A Simplified and Practical Surgical Treatment for Medial Ectropion: A Case Report.

Plast Reconstr Surg Glob Open 2019 May 21;7(5):e2102. Epub 2019 May 21.

Division of Plastic Surgery, University of Modena and Reggio Emilia, Largo Pozzo 71, 41124 Modena, Italy.

We present the case of a 81-year-old patient with right facial palsy suffering from recurrent medial ectropion with lower lateral dislocation of the lacrimal punctum causing epiphora and photophobia. The patient was first treated for ectropion with lateral tarsal strip procedure. Unfortunately, this surgical procedure did not get the expected result. This was the reason we used the Mitek anchor system to fix the lower lateral dislocation of the punctum. We had no recurrence of symptoms during a follow-up period of 18 months.
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http://dx.doi.org/10.1097/GOX.0000000000002102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6571293PMC
May 2019

Surgical Wound Infections in Plastic Surgery: Simplified, Practical, and Standardized Selection of High-risk Patients.

Plast Reconstr Surg Glob Open 2019 Apr 23;7(4):e2202. Epub 2019 Apr 23.

Division of Plastic Surgery, University of Modena and Reggio Emilia, Modena, Italy.

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http://dx.doi.org/10.1097/GOX.0000000000002202DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6554174PMC
April 2019

Impact of HOXB7 overexpression on human adipose-derived mesenchymal progenitors.

Stem Cell Res Ther 2019 03 19;10(1):101. Epub 2019 Mar 19.

Division of Oncology, Department of Medical and Surgical Sciences for Children and Adults, University-Hospital of Modena and Reggio Emilia, Via del Pozzo, 71, 41100, Modena, Italy.

Background: The ex vivo expansion potential of mesenchymal stromal/stem cells (MSC) together with their differentiation and secretion properties makes these cells an attractive tool for transplantation and tissue engineering. Although the use of MSC is currently being tested in a growing number of clinical trials, it is still desirable to identify molecular markers that may help improve their performance both in vitro and after transplantation.

Methods: Recently, HOXB7 was identified as a master player driving the proliferation and differentiation of bone marrow mesenchymal progenitors. In this study, we investigated the effect of HOXB7 overexpression on the ex vivo features of adipose mesenchymal progenitors (AD-MSC).

Results: HOXB7 increased AD-MSC proliferation potential, reduced senescence, and improved chondrogenesis together with a significant increase of basic fibroblast growth factor (bFGF) secretion.

Conclusion: While further investigations and in vivo models shall be applied for better understanding, these data suggest that modulation of HOXB7 may be a strategy for innovative tissue regeneration applications.
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http://dx.doi.org/10.1186/s13287-019-1200-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6423808PMC
March 2019

MSC-Delivered Soluble TRAIL and Paclitaxel as Novel Combinatory Treatment for Pancreatic Adenocarcinoma.

Theranostics 2019 1;9(2):436-448. Epub 2019 Jan 1.

Division of Oncology, Department of Medical and Surgical Sciences for Children & Adults, University-Hospital of Modena and Reggio Emilia, Modena, Italy.

Pancreatic cancer is the fourth leading cause of cancer death in western countries with more than 100,000 new cases per year in Europe and a mortality rate higher than 90%. In this scenario, advanced therapies based on gene therapies are emerging, thanks to a better understanding of tumour architecture and cancer cell alterations. We have demonstrated the efficacy of an innovative approach for pancreatic cancer based on mesenchymal stromal cells (MSC) genetically engineered to produce TNF-related Apoptosis Inducing Ligand (TRAIL). Here we investigated the combination of this MSC-based approach with the administration of a paclitaxel (PTX)-based chemotherapy to improve the potential of the treatment, also accounting for a possible resistance onset. Starting from the BXPC3 cell line, we generated and profiled a TRAIL-resistant model of pancreatic cancer, testing the impact of the combined treatment with specific cytotoxicity and metabolic assays. We then challenged the rationale in a subcutaneous mouse model of pancreatic cancer, assessing its effect on tumour size accounting stromal and parenchymal organization. PTX was able to restore pancreatic cancer sensitivity to MSC-delivered TRAIL by reverting its pro-survival gene expression profile. The two compounds cooperate both and and the combined treatment resulted in an improved cytotoxicity on tumour cells. In summary, this study uncovers the potential of a combinatory approach between MSC-delivered TRAIL and PTX, supporting the combination of cell-based products and conventional chemotherapeutics as a tool to improve the efficacy of the treatments, also addressing possible mechanisms of resistance.
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http://dx.doi.org/10.7150/thno.27576DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6376176PMC
December 2019

Soluble TRAIL Armed Human MSC As Gene Therapy For Pancreatic Cancer.

Sci Rep 2019 02 11;9(1):1788. Epub 2019 Feb 11.

Division of Oncology, Department of Medical and Surgical Sciences for Children & Adults, University-Hospital of Modena and Reggio Emilia, Modena, Italy.

Pancreatic ductal adenocarcinoma (PDAC) is still one of the most aggressive adult cancers with an unacceptable prognosis. For this reason novel therapies accounting for PDAC peculiarities, such as the relevant stromal reaction, are urgently needed. Here adipose mesenchymal stromal/stem cells (AD-MSC) have been armed to constantly release a soluble trimeric and multimeric variant of the known anti-cancer TNF-related apoptosis-inducing ligand (sTRAIL). This cancer gene therapy strategy was in vitro challenged demonstrating that sTRAIL was thermally stable and able to induce apoptosis in the PDAC lines BxPC-3, MIA PaCa-2 and against primary PDAC cells. sTRAIL released by AD-MSC relocated into the tumor stroma was able to significantly counteract tumor growth in vivo with a significant reduction in tumor size, in cytokeratin-7+ cells and by an anti-angiogenic effect. In parallel, histology on PDAC specimens form patients (n = 19) was performed to investigate the levels of TRAIL DR4, DR5 and OPG receptors generating promising insights on the possible clinical translation of our approach. These results indicate that adipose MSC can very efficiently vehicle a novel TRAIL variant opening unexplored opportunities for PDAC treatment.
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http://dx.doi.org/10.1038/s41598-018-37433-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6370785PMC
February 2019

Composite lower back and buttock reconstruction with gluteal myocutaneous flap in the just born.

Plast Reconstr Surg 2009 Nov;124(5):269e-270e

Division of Plastic and Reconstructive Surgery (Baccarani, Jacob, Pedone, Pinelli, De Santis) Division of Pediatric Surgery; University of Modena and Reggio Emilia; Modena, Italy (Bianchini, Cacciari).

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http://dx.doi.org/10.1097/PRS.0b013e3181b98ebbDOI Listing
November 2009

Polyacrylamide hydrogel injection in the management of human immunodeficiency virus-related facial lipoatrophy: a 2-year clinical experience.

Plast Reconstr Surg 2008 Feb;121(2):644-653

Modena, Italy From the Department of Plastic and Reconstructive Surgery, University of Modena and Reggio Emilia.

Background: Facial lipoatrophy is defined as the reduction in buccal and orbital fat pads along with a more global loss of fat within the subcutaneous tissue. It is the most common and distressing sign of human immunodeficiency virus-associated lipodystrophy. Injectable polyacrylamide hydrogel (Aquamid) is a synthetic nonbiodegradable polymer consisting of a minor backbone of 2.5 percent cross-linked polyacrylamide and 97.5 percent nonpyrogenic water and is used for cosmetic facial contour correction. Favorable results with maximum aesthetic gains with the use of polyacrylamide hydrogel for reconstruction of facial lipoatrophy on the face in significantly immunocompromised individuals are being reported. These results are attributable to its use in limited volume injected at multiple sites and in multiple sittings.

Methods: Aquamid has been used for the correction of severe nasolabial folds and mid and lower facial volume loss in patients affected by human immunodeficiency virus-associated lipodystrophy. Fifty patients were enrolled and treated, with a mean follow-up of 13.1 months. Results were evaluated clinically, by standardized ultrasonography, and by psychological tests (visual analogue scale, Beck Depression Inventory, and Assessment of Body Change and Distress questionnaire) to quantify patient satisfaction.

Results: No significant side effects or issues such as swelling, infections, allergies, or nodule formation were noted over the follow-up period.

Conclusion: Aquamid has provided a minimally invasive, effective, long-lasting facial contour correction that significantly improves the quality of life in human immunodeficiency virus-infected patients.
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http://dx.doi.org/10.1097/01.prs.0000298108.46379.15DOI Listing
February 2008

Free vascularized tissue transfer to preserve upper extremity amputation levels.

Plast Reconstr Surg 2007 Sep;120(4):971-981

Durham, N.C.; Modena and Florence, Italy; and Heidelberg, Germany From the Division of Plastic, Reconstructive, Maxillofacial, and Oral Surgery, Duke University Medical Center; Division of Plastic and Reconstructive Surgery, University of Modena and Reggio Emilia; Division of Reconstructive Microsurgery, Careggi University Hospital; and Department of Plastic, Reconstructive, and Hand Surgery, BG Trauma Center Ludwigshafen, University of Heidelberg.

Background: Free vascularized tissue transfer to preserve upper extremity amputation level is an uncommon procedure. The authors investigate the role of free tissue transfer in preserving both morphology and function of the amputated upper extremity, with the goal of facilitating prosthetic rehabilitation.

Methods: Thirteen patients who underwent microsurgical free tissue transfer to preserve upper extremity amputation level were reviewed retrospectively. These cases were selected from four centers: Duke University Medical Center (Durham, N.C.) University Hospital of Modena (Modena, Italy), Careggi University Hospital (Florence, Italy), and the University of Heidelberg (Heidelberg, Germany). Parameters that were evaluated included age, sex, cause of the defect, reconstructive procedure, structures to be salvaged, and functional outcome, among others.

Results: The cause of amputation was trauma in 92 percent of patients. Mean age was 32 years. In 31 percent of the cases, an emergency free fillet flap was used, and in the remaining 69 percent, a traditional free flap was performed. Structures/function to be preserved included pinch function to the hand, function of the elbow and shoulder joints, and skeletal length greater than 7 cm. Complications occurred in 38 percent of the cases, but the final goal of the procedure was achieved in all cases. A treatment algorithm for the management of the amputated upper extremity is presented.

Conclusion: Use of free vascularized tissue transfer for preservation of upper extremity amputation level in well-selected cases facilitates prosthetic rehabilitation and improves residual limb function.
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http://dx.doi.org/10.1097/01.prs.0000256479.54755.f6DOI Listing
September 2007
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