Publications by authors named "Natale Porta"

39 Publications

Nuclear lamin A in rotator cuff tear margin tenocytes: an antiapoptotic and cell mechanostat factor.

J Orthop Surg Res 2021 Jun 30;16(1):413. Epub 2021 Jun 30.

Department of Anatomical, Histological, Forensic Medicine and Orthopaedics Sciences, Sapienza University of Rome, Istituto Clinico Ortopedico Traumatologico (ICOT), Latina, Italy.

Background: The network of intermediate filament proteins underlying the inner nuclear membrane forms the nuclear lamin. A- and B-type lamins are the major components of the nuclear lamina. Lamins function in many nuclear activities. The role of lamin A and transcription factors (NF-kB) as anti-apoptotic is well documented. Recently, lamin A has also been considered as a mechanosensor protein that is able to maintain nuclear integrity from mechanical insults. We aimed to verify how lamin A expression varies in healthy cuff cells and in those with different-sized tears where various mechanical stresses are present.

Methods: Forty-three patients with rotator cuff tear (RCT) [23M-20F, mean age (SD): 63.5 (6.1)] were enrolled. Tissue samples excised from the most medial point of tear margins were analyzed for lamin A expression by immunohistochemistry. Controls were represented by samples obtained by normal supraspinatus tendons excised from patients submitted to reverse shoulder prosthesis implant [8M-7F, mean age (SD): 67.9 (7.1)]. The intensity of staining was graded, and an H-score was assigned. Statistical analysis was performed.

Results: Our study revealed a moderate intensity of lamin A in the healthy cuff tendons, a higher expression of this protein in the small tears, and a significant decrease of lamin A with increasing tear size (p < 0.0001).

Conclusions: Our study emphasizes the importance of early repair of small RCTs since nuclear stability is maintained, and the cellular function is protected by lamin A overexpression. High re-tear of massive cuff repair could be due to cellular apoptosis and nuclear modifications induced by lamin A lack.

Level Of Evidence: III.
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http://dx.doi.org/10.1186/s13018-021-02569-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8243552PMC
June 2021

Metastatic penile squamous cell carcinoma successfully treated with cemiplimab in an HIV patient.

Dermatol Ther 2021 03 17;34(2):e14744. Epub 2021 Jan 17.

Department of Medical-Surgical Sciences and Biotechnologies, Dermatology Unit "Daniele Innocenzi", Sapienza University of Rome, Rome, Italy.

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http://dx.doi.org/10.1111/dth.14744DOI Listing
March 2021

Targeting SMYD3 to Sensitize Homologous Recombination-Proficient Tumors to PARP-Mediated Synthetic Lethality.

iScience 2020 Oct 7;23(10):101604. Epub 2020 Oct 7.

Medical Genetics, National Institute of Gastroenterology "S. de Bellis" Research Hospital, Castellana Grotte, Bari 70013, Italy.

is frequently overexpressed in a wide variety of cancers. Indeed, its inactivation reduces tumor growth in preclinical animal models. However, extensive characterization failed to clarify function in cancer cells, although confirming its importance in carcinogenesis. Taking advantage of a mutant variant identified in a high-risk breast cancer family, here we show that SMYD3 phosphorylation by ATM enables the formation of a multiprotein complex including ATM, SMYD3, CHK2, and BRCA2, which is required for the final loading of RAD51 at DNA double-strand break sites and completion of homologous recombination (HR). Remarkably, SMYD3 pharmacological inhibition sensitizes HR-proficient cancer cells to PARP inhibitors, thereby extending the potential of the synthetic lethality approach in human tumors.
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http://dx.doi.org/10.1016/j.isci.2020.101604DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648160PMC
October 2020

Robot-assisted retroperitoneal lymphadenectomy in patient with type I papillary renal cancer recurrence after 5 years of follow-up.

J Surg Case Rep 2020 Oct 10;2020(10):rjaa336. Epub 2020 Oct 10.

Department of Medico-Surgical Sciences and Biotechnologies, "La Sapienza" University of Rome, Urology Unit ICOT, Latina, Italy.

Papillary renal cell carcinoma (PRCC) is a rare cancer and is the second most frequent histologic type among all renal cell carcinoma, accounting for up to 15%. A 72-year-old man underwent a right radical nephrectomy 7 years ago with final histopathology diagnosis of type 1 PRCC with negative surgical margins. Five years after surgery, computed tomography scan imaging showed the presence of multiple masses suspicious for node recurrences disease localized in the renal lodge, in the inter-aorto-caval space, at the iliac vessels bifurcation and right common iliac vessels. Patient underwent a robotic retroperitoneal lymphadenectomy. The histopathological examination confirmed the recurrence of type I papillary renal cancer in all the specimens. No further recurrences have been observed at 24-month follow-up after surgery. This report is the first describing a robot-assisted minimally invasive surgical excision for type I papillary renal cancer nodal and renal fossa recurrences.
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http://dx.doi.org/10.1093/jscr/rjaa336DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7546679PMC
October 2020

Shear wave elastography in varicocele patients: Prospective study to investigate correlation with semen parameters and histological findings.

Int J Clin Pract 2021 Mar 13;75(3):e13699. Epub 2020 Oct 13.

Histology Unit, Department of Medico-Surgical Sciences and Biotechnologies, Faculty of Pharmacy and Medicine, Sapienza University of Rome, Latina, Italy.

Aims: Shear wave elastosonography (SWE) is a non-invasive ultrasound imaging modality used to assess the mechanical properties of tissues such as rigidity and elasticity. In this prospective study, we investigated the effect of laparoscopic varicocelectomy on the elasticity, degree of fibrosis and function of the testes through SWE and we evaluated the correlation with semen parameters and histology findings.

Methods: Male patients with monolateral left varicocele and progressive alteration of the semen quality were enrolled prospectively. Patients were evaluated before varicocelectomy, 3 and 6 months after surgery with semen analysis, ecocolordoppler US and SWE. In all patients, a left testicular biopsy was performed at the time of varicocelectomy and it was repeated after 6 months in 55% of patients in order to investigate the histological findings and to correlate with SWE results.

Results: The study was conducted on 82 patients. SWE showed a statistically significant difference between left and right testicles. Three months after surgery the mean left testicular volume increased, mean left SWE features decreased, and sperm count increased (P values < .0001). The SWE parameters, testicular volume and semen analysis values showed a statistically significant positive correlation between the pre and postoperative results (P value < .0001). The histological alterations were significantly changed 6 months postoperative with a complete morphology recovery in accordance with SWE results.

Conclusions: SWE showed a statistically significant positive correlation with testicular volume, semen analysis and histological findings. This study represents the first investigation that correlates the varicocele, the testis volume, the quality of the seminal fluid ant the histological findings with the ultrasound and SWE values.
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http://dx.doi.org/10.1111/ijcp.13699DOI Listing
March 2021

Melanoma: Double BRAF mutation, double chance to treat?

Dermatol Ther 2020 11 6;33(6):e13820. Epub 2020 Jul 6.

Department of Medical-Surgical Sciences and Biotechnologies, Dermatology Unit "Daniele Innocenzi", Sapienza University of Rome, Polo Pontino, Italy.

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http://dx.doi.org/10.1111/dth.13820DOI Listing
November 2020

A case of hidradenitis suppurativa successfully treated with apremilast in a patient with psoriasis and SAMPUS.

Dermatol Ther 2020 05 8;33(3):e13448. Epub 2020 May 8.

Department of Medical-Surgical Sciences and Biotechnologies, Dermatology Unit "Daniele Innocenzi", Sapienza University of Rome, Polo Pontino, Italy.

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http://dx.doi.org/10.1111/dth.13448DOI Listing
May 2020

Transitory auricular nodules: a peculiar adverse reaction in actinic keratosis field treatment.

Int J Dermatol 2020 Aug 19;59(8):e279-e281. Epub 2020 Apr 19.

Dermatology Unit "Daniele Innocenzi", Department of Medical-Surgical Sciences and Bio-Technologies, Sapienza University of Rome, Polo Pontino, Italy.

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http://dx.doi.org/10.1111/ijd.14882DOI Listing
August 2020

Primary vaginal leiomyosarcoma: A case report with complete morphological, immunohistochemical and ultrastructural study.

Taiwan J Obstet Gynecol 2020 Mar;59(2):314-317

Department SAIMLAL, Section of Anatomy, Laboratory of Electron Microscopy Pietro Motta, Sapienza University of Rome, Rome, Italy.

Objective: Primary vaginal leiomyosarcomas (LMS) are rare, easily recurrent tumours with an unknown etiology; the prognosis is poor and there is no consensus guideline on their management.

Case Report: A nodular, 25 × 23 x 28 mm-mass, infiltrating the urethra, was found in a 58-year-old woman. A biopsy showed a LMS of the vagina that was positive for vimentin, alpha-smooth muscle actin, caldesmon, desmin, p16 and p53. An anterior pelvic exenteration was performed. The sample was fixed and prepared for light microscopy, transmission and scanning electron microscopy, confirming the diagnosis of LMS.

Conclusions: Best outcomes occur when the tumour is small, localized, and can be removed surgically with wide, clear margins, as in this case. As there are different kinds of malignant mesenchymal tumours, biopsy followed by immunohistochemistry and electron microscopy still represents a good diagnostic choice and surgical resection is generally the gold standard in these cases.
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http://dx.doi.org/10.1016/j.tjog.2020.01.023DOI Listing
March 2020

Black and Pink: Single Lesion or Double Diagnosis?

Dermatol Pract Concept 2020 31;10(1):e2020025. Epub 2019 Dec 31.

Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University, Rome, Italy.

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http://dx.doi.org/10.5826/dpc.1001a25DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6936632PMC
December 2019

Ingenol mebutate therapy in erythroplasia of Queyrat: a new approach.

Ital J Dermatol Venerol 2021 Jun 4;156(3):388-391. Epub 2019 Dec 4.

Unit of Dermatology Daniele Innocenzi, Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University, Fiorini Hospital - Polo Pontino, Rome, Italy.

Background: Erythroplasia of Queyrat (EQ) is a rare squamous cell carcinoma in situ, usually occurring on the glans penis, the prepuce, or the urethral meatus. Therapy is mandatory because it can progress to invasive carcinoma in up to 30% of cases. Treatment options include 5-fluorouracil, curettage, cryotherapy, radiotherapy, laser, partial or total penectomy, and microsurgery, as also with imiquimod and photodynamic therapies.

Methods: Between 2015 to 2018 we treated five patients, with histologically confirmed EQ, with ingenol mebutate (IM) 0.015% gel applied for 3 days consecutively.

Results: Three patients showed complete response at one year follow up. Two patients showed partial response after two months, so they received a second course of therapy with IM. At one-year follow-up, one of them showed complete response, the other partial response.

Conclusions: Our experience demonstrated that IM may be considered as an effective and safe treatment option in EQ. IM offers various advantages such as easy and fast application, rapid complete remission, better compliance, few side effects and excellent cosmetical results. The authors call for further exploitation in bigger trials.
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http://dx.doi.org/10.23736/S0392-0488.19.06371-5DOI Listing
June 2021

On the role of skin biopsy in the diagnosis of calcific uremic arteriolopathy: a case-based discussion.

J Nephrol 2020 Aug 2;33(4):859-865. Epub 2019 Dec 2.

Dialysis Unit at ICOT Hospital, Latina, Italy.

Calciphylaxis is a rare disease characterized by ectopic calcification of skin arterioles resulting in ischemia, thrombosis and necrosis. Since end stage renal disease patients are those mainly affected, the term calcific uremic arteriolopathy (CUA) is also suggested. Early clinical manifestations are subtle, while overt necrotic ulcers may quickly spread and become infected so as to result in ominous outcome. Diagnosis might not be easy due to the number of other ischemic and non-ischemic skin lesions observed in uraemia. Skin biopsy, has been proposed as the diagnostic test and is often considered, but not systematically performed due to the hypothetical risk of further spreading of the lesions. Such ambiguity could be responsible for misdiagnosis or underdiagnosis. We review here five consecutive cases recorded in our Unit, all submitted to skin biopsy but with inconsistent results which generated some clinical frustration. Thus, we decided to carefully re-evaluate all of them together with pathologists and dermatologists. However, even after this ex-post discussion, we could not reach a complete agreement on the final diagnosis. In the meanwhile, papers were published in the literature that started to shed some light on the role of skin biopsy in the diagnosis of CUA.
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http://dx.doi.org/10.1007/s40620-019-00678-zDOI Listing
August 2020

Emerging role of secreted miR-210-3p as potential biomarker for clear cell Renal Cell Carcinoma metastasis.

Cancer Biomark 2020 ;27(2):181-188

Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, Section of Histology and Medical Embryology, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University of Rome, Rome, Italy.

Background: MicroRNAs (miRNAs) are emerging as promising molecules in the diagnosis, prognosis and treatment of urological tumours. Recently, our group performed two independent studies highlighting that miR-210-3p may be a useful biomarker not only for diagnosis but also for post-surgery clear cell Renal Cell Carcinoma (ccRCC) management.

Objective: The aim of this study is to further explore the effectiveness of miRNA as non-invasive biomarker for clinical outcomes and ccRCC response to the treatment.

Methods: We analyzed miR-210-3p levels in neoplastic and healthy tissue and in urine specimens collected at surgery and during follow-up of 21 ccRCC patients by RTqPCR.

Results: Firstly, we confirmed that the expression of miR-210-3p was upregulated in tumor tissues and in urine samples of analyzed cohort. Of note is that miR-210-3p expression was significantly reduced in urine samples from disease-free patients during follow-up (from 3 to 12 months) compared to the baseline levels observed at the time of surgery. In a small subgroup of patients presenting metastatic progression (such as bone, intestinal or lung metastasis), the urine levels of miR-210-3p correlated with responsiveness to the therapy.

Conclusions: This pilot study highlights the relevance of secreted miR-210-3p as powerful non-invasive prognostic and predictive biomarker for the evaluation of clinical outcomes and treatment response during ccRCC follow up.
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http://dx.doi.org/10.3233/CBM-190242DOI Listing
July 2020

Eruptive Blue Nevi of the Scalp in a Patient with Mayer-Rokitansky-Küster-Hauser Syndrome during Isotretinoin Therapy.

Indian J Dermatol 2019 Jul-Aug;64(4):339

Department of Medical-Surgical Sciences and Bio-Technologies, Dermatology Unit "Daniele Innocenzi", Sapienza University of Rome, Fiorini Hospital, Polo Pontino, Terracina, Italy. E-mail:

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http://dx.doi.org/10.4103/ijd.IJD_188_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6714184PMC
September 2019

The attempt of spontaneous repair of rotator cuff tear: The role of periostin.

J Orthop 2019 Sep-Oct;16(5):400-404. Epub 2019 May 2.

Dept. of Anatomical, Histological, Forensic Medicine and Orthopaedics Sciences, Sapienza University of Rome, Istituto Clinico Ortopedico Traumatologico (ICOT), Latina, Italy.

The development of a periostin-rich microenvironment in areas associated with insult, orchestrating pathways of repair and rebuilding, is documented. Literature lacks information regarding the presence of periostin in the context of rotator cuff tear (RCT). 55 consecutive patients with RCT were enrolled. Immunohistochemical periostin detection was performed on tissue samples excised from tear margins. Our study documented the presence of periostin in the margins of RCT. It is plausible that, when a tear occurs, multiple stimuli, both mechanical and inflammatory, lead to the development of a periostin-rich microenvironment as an attempt to tendon healing.
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http://dx.doi.org/10.1016/j.jor.2019.04.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6512582PMC
May 2019

Successful treatment with pollen extract of hematospermia in patients with xanthogranolomatous prostatitis.

Arch Ital Urol Androl 2019 Mar 29;91(1):22-24. Epub 2019 Mar 29.

Sapienza University of Rome, Faculty of Pharmacy and Medicine, Department of Medico-Surgical Sciences and Biotechnologies, Urology Unit, Latina; Uroresearch, no profit Association for Research in Urology, Latina.

Introduction: The aim of this study was to report our experience in the management of hematospermia observed in 16 patients suffering from xanthogranulomatous prostatitis.

Methods: Recurrent episodes of hematospermia were the onset symptom in all patients, and in 25% of patients it was combined with fever. All patients reported PSA value elevation and the digital rectal examination (DRE) revealed an increase of the gland size and of its consistency in all cases. In all patients, the hematospermia was treated with the oral administration of two tablets of pollen extract in a single (1 g) dose daily for 30 days.

Results: Sixteen patients were observed between 2008 and 2016, referring hematospermia, progressive lower urinary tract symptoms (LUTS), and serum PSA level increase. To exclude the prostate cancer presence all patients were submitted to transperineal TRUS guided biopsy. In all the patients complete resolution of hematospermia was achieved treatment with pollen extract. All patients were subsequently treated for LUTS (alpha-adrenergic blockers), but none reported any significant improvement of symptoms. Basing on these pieces of evidence, after 90 days of alpha-blockers therapy, all patients underwent bipolar TURP. Histological examination of resected prostatic tissue revealed in all patients the diagnosis of xanthogranulomatous prostatitis.

Conclusions: Patients with xanthogranulomatous prostatitis especially experience irritative symptoms, sometimes combined with fever or hematospermia. Hematospermia as the onset symptom has not been reported so far. The administration of the pollen extract for 30 days was associated with a complete resolution of hematospermia.
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http://dx.doi.org/10.4081/aiua.2019.1.22DOI Listing
March 2019

Argonaute 2 drives miR-145-5p-dependent gene expression program in breast cancer cells.

Cell Death Dis 2019 01 8;10(1):17. Epub 2019 Jan 8.

Department of Anatomical, Histological, Forensic & Orthopedic Sciences, Section of Histology & Medical Embryology, Sapienza University of Rome, laboratory affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Rome, Italy.

To perform their regulatory functions, microRNAs (miRNAs) must assemble with any of the four mammalian Argonaute (Ago) family of proteins, Ago1-4, into an effector complex known as the RNA-induced silencing complex (RISC). While the mature miRNA guides the RISC complex to its target mRNA, the Ago protein represses mRNA translation. The specific roles of the various Ago members in mediating miRNAs activity, however, haven't been clearly established. In this study, we investigated the contribution of Ago2, the only human Ago protein endowed with nuclease activity, to the function of tumor-suppressor miR-145-5p in breast cancer (BC). We show that miR-145-5p and Ago2 protein are concomitantly downregulated in BC tissues and that restoration of miR-145-5p expression in BC cells leads to Ago2 protein induction through the loosening of Ago2 mRNA translational repression. Functionally, miR-145-5p exerts its inhibitory activity on cell migration only in presence of Ago2, while, upon Ago2 depletion, we observed increased miR-145/Ago1 complex and enhanced cell motility. Profiling by microarray of miR-145-5p target mRNAs, in BC cells depleted or not of Ago2, revealed that miR-145-5p drives Ago2-dependent and -independent activities. Our results highlight that the Ago2 protein in cancer cells strictly dictates miR-145-5p tumor suppressor activity.
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http://dx.doi.org/10.1038/s41419-018-1267-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6325137PMC
January 2019

Sclerostin is expressed in the atherosclerotic plaques of patients who undergoing carotid endarterectomy.

Diabetes Metab Res Rev 2019 01 2;35(1):e3069. Epub 2018 Oct 2.

Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.

Background: Sclerostin (SC) is a monomeric glycoprotein expressed by osteocytes that affects bone formation. Recent studies have suggested a potential role for this protein in the pathophysiology of vascular diseases. The aim of the present study was to investigate SC expression in atherosclerotic plaques of patients affected by severe atherosclerotic disease who underwent carotid endarterectomy. We also evaluated possible differences in SC expression between patients with and without type 2 diabetes (T2D).

Methods: This was a cross-sectional study involving 46 patients aged 55 to 80 years (mean, 71.1 ± 6.7 years, 36 men, 15 patients with T2D) who underwent carotid endarterectomy. Immunohistochemical levels of SC were evaluated in the atherosclerotic plaques by double-staining immunochemistry, and serum SC levels were evaluated by enzyme-linked immunosorbent assay.

Results: Sclerostin was present in the atherosclerotic plaques of all subjects investigated and increased significantly in the media compared with the intima (P < 0.0001) as well as in vascular smooth muscle cells (VSMCs) compared with the infiltrating macrophages (P < 0.0001). However, no significant difference in SC expression was observed between patients with and without T2D. No correlation was found between serum and immunohistochemical levels of SC; significantly increased SC serum levels were detected in males compared with females (P = 0.049).

Conclusions: We have demonstrated, for the first time, the expression of SC in VSMCs of atherosclerotic plaques, suggesting a potential role for this protein in the development of atherosclerosis. Further studies are needed to understand if the role played by SC is detrimental or protective in the atherosclerotic disease process.
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http://dx.doi.org/10.1002/dmrr.3069DOI Listing
January 2019

Parathyroid Autotransplantation During thyroid Surgery. Where we are? A Systematic Review on Indications and Results.

J Invest Surg 2019 Nov 16;32(7):594-601. Epub 2018 Apr 16.

Department of Surgery "P. Valdoni", Sapienza University , Rome , Italy.

: Hypoparathyroidism still represents an important concern in thyroid surgery. Careful dissection with identification and preservation of parathyroid glands in situ remains the best way to maintain gland vitality and avoid post-operative failure. Nevertheless, parathyroid glands are still inadvertently removed in up to 11% of cases. Parathyroid autotransplantation may represent the only way to restore parathyroid gland functionality in case of inadvertent removal or devascularization during thyroid surgery. Despite this, there is still no agreement on the effectiveness of this procedure. The present systematic review is focused on the mainly debated matters regarding the procedure, indications, technique and results. : This review has been carried out according to PRISMA statement and checklist. The research item was: (((parathyroid autotransplantation[Title]) OR parathyroid reimplantation[Title]) NOT hyperparathyroidism[Title]) AND english[Language]. : A total of 31 studies have been found according to limitations already described, reporting from 4 to 890 procedures, with a total amount of 4088 PA. Among these studies, there are only 7 prospective case-series evaluations, 2 prospective randomized trials, while the other 22 studies are retrospective evaluations. The main concerns are: when and how to perform autotransplantation; in which anatomical site; which result to be expected, and how to manage and control the graft. : Parathyroid autotransplantatin is an important tool to avoid or minimize the risk for hypoparathyroidism following thyroid surgery in selected cases. Parathormone assay can help the surgeon to determine when reimplantation is indicated or not. Further studies could theoretically give definitive results.
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http://dx.doi.org/10.1080/08941939.2018.1441344DOI Listing
November 2019

USPIO-labeling in M1 and M2-polarized macrophages: An in vitro study using a clinical magnetic resonance scanner.

J Cell Physiol 2018 08 27;233(8):5823-5828. Epub 2018 Feb 27.

Faculty of Medicine and Dentistry, Department of Radiological Sciences, Oncology and Pathology, University of Rome "Sapienza", Latina, Italy.

Aim of the study was to evaluate USPIO labeling in different macrophage populations using a clinical 3.0T MR unit with optical and electron microscopy as the gold standard. Human monocytic cell line THP-1 cells were differentiated into macrophages. Afterwards, M0 macrophages were incubated with IL-4 and IL-13 in order to obtain M2 polarized macrophages or with IFN-gamma and LPS for classical macrophage activation (M1). These groups were incubated with USPIO-MR contrast agent (P904) for 36 hr; M0, M0 + P904, M1 +  P904, and M2 + P904 were analyzed in gel phantoms with a 3.0T MR scanner. m-RNA of M1 and M2 markers confirmed the polarization of THP-1-derived macrophages. M2 + P904 showed a much higher T1 signal (p <  0.0001), a significantly lower (p < 0.0001) T2* signal, and significantly higher R* (p < 0.0001) compared to the other populations. Hystological analysis confirmed higher iron content in the M2-polarized population compared to both M1-polarized (p = 0.04) and M0-P904 (p = 0.003). Ultrastructure analysis demonstrated ubiquitous localization of P904 within the cellular compartments. Our results demonstrate that a selective USPIO-labeling of different macrophage populations can be detected in vitro using the 3.0T clinical scanner.
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http://dx.doi.org/10.1002/jcp.26360DOI Listing
August 2018

Secreted miR-210-3p as non-invasive biomarker in clear cell renal cell carcinoma.

Oncotarget 2017 Sep 13;8(41):69551-69558. Epub 2017 Jun 13.

Department of Anatomical, Histological, Forensic & Orthopaedic Sciences, Section of Histology & Medical Embryology, Sapienza University of Rome, Rome, Italy.

The most common subtype of renal cell carcinoma (RCC) is clear cell RCC (ccRCC). It accounts for 70-80% of all renal malignancies representing the third most common urological cancer after prostate and bladder cancer. The identification of non-invasive biomarkers for the diagnosis and responsiveness to therapy of ccRCC may represent a relevant step-forward in ccRCC management. The aim of this study is to evaluate whether specific miRNAs deregulated in ccRCC tissues present altered levels also in urine specimens. To this end we first assessed that miR-21-5p, miR-210-3p and miR-221-3p resulted upregulated in ccRCC fresh frozen tissues compared to matched normal counterparts. Next, we evidenced that miR-210-3p resulted significantly up-regulated in 38 urine specimens collected from two independent cohorts of ccRCC patients at the time of surgery compared to healthy donors samples. Of note, miR-210-3p levels resulted significantly reduced in follow-up samples. These results point to miR-210-3p as a potential non-invasive biomarker useful not only for diagnosis but also for the assessment of complete resection or response to treatment in ccRCC management.
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http://dx.doi.org/10.18632/oncotarget.18449DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5642499PMC
September 2017

Parathyroid reimplantation with PR-FaST technique in unselected patients during thyroidectomy. A case series with long term follow up confirming graft vitality and parathormone production.

Int J Surg 2017 Mar 3;39:202-205. Epub 2017 Feb 3.

Department of Surgery "P. Valdoni", Sapienza University, Rome, Italy.

Introduction: Parathyroid damage or unintentional excision still affect thyroid surgery and may cause permanent hypoparathyroidism. The only way to recover the excised or ischemic gland functionality is still reimplantation. Many sites of reimplantation have been described, each of one showing both advantages and drawbacks. The aim of this study is to verify results of a new procedure called PR-FaST: Parathyroid Reimplantation in Forearm Subcutaneous Tissue, in a series of unselected patients after long-term follow-up.

Materials And Methods: From January 2013 to October 2015, 296 consecutive total thyroidectomies have been performed) to treat both benign and malignant thyroid diseases. in 42 cases (14.1%), due to an insufficient blood supply or accidental removal, one parathyroid gland was reimplanted with the PR-FaST technique. Post-operative evaluation was carried out by: total serum calcium (Ca), magnesium (Mg) and phosphorus (P) analysis in the 1st and 2nd postoperative days; Ca, Mg, P and serum iPTH from both arms analysis one week after surgery; Ca and iPTH measurement from both arms 1 months, 3, 6 and 12 months after surgery.

Results: We observed transient hypocalcemia requiring calcium replacement therapy in 5 on 42 (11.9%) patients submitted to PR-FaST. No case of permanent hypoparathyroidism was reported. At 1 week after surgery, only 20 patients (47.6%) showed graft vitality, while the number of patients showing graft vitality arised to 33 (79%) after 1 month and to 39 (92.8%) after three and six months. At 1 year 38 (90.5%) patients showed good graft functionality. Considering levels of serum iPTH from both arms, we observed that in case of graft functionality, samples from reimplanted arm revealed in almost all cases values at least 2-3 folds higher than in non reimplanted arm.

Conclusions: Results from this prospective evaluation suggest that PR-FaST is a safe and effective procedure, with potential advantages when compared to other techniques of parathyroid reimplantation, that are mainly the possibility to evaluate graft functionality in the follow-up and the easy and well reproducible technique. Furthermore, it can be applied, when needed, to potentially all patients undergoing thyroidectomy.
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http://dx.doi.org/10.1016/j.ijsu.2017.01.117DOI Listing
March 2017

Mass spectrometry profiling of oxysterols in human sperm identifies 25-hydroxycholesterol as a marker of sperm function.

Redox Biol 2017 04 22;11:111-117. Epub 2016 Nov 22.

Vascular Biology & Mass Spectrometry Laboratory (CZ, RP, MC, LI), Urology Unit (AP, GP, AC), and Histopathology Unit (VP, NP), Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy. Electronic address:

Cholesterol is a main lipid component of sperm cell that is essential for sperm membrane fluidity, capacitation, and acrosomal reaction. Recent data obtained in bovine sperm showed that sperm capacitation is associated to the formation of oxysterols, oxidized products of cholesterol. The aim of this study was to profile oxysterol content in human semen, and to investigate their potential role in sperm pathophysiology. Among the 12 oxysterols analyzed, 25-hydroxycholesterol (25-HC) resulted the most represented in normozoospermic samples, and its concentration positively correlated with spermatozoa number. We detected Cholesterol 25-hydroxylase, the enzyme responsible for 25-HC production, in human spermatozoa at the level of the neck and the post acrosomal area. Upon incubation with spermatozoa, 25-HC induced calcium and cholesterol transients in connection with the acrosomal reaction. Our results support a role for 25-HC in sperm function.
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http://dx.doi.org/10.1016/j.redox.2016.11.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5133663PMC
April 2017

Computed Tomography Perfusion of Prostate Cancer: Diagnostic Value of Quantitative Analysis.

J Comput Assist Tomogr 2016 Sep-Oct;40(5):740-5

From the *Department of Radiological Sciences, Oncology and Pathology, †Urology Unit, Department of Medical-Surgical Sciences and Biotechnologies, Faculty of Pharmacy and Medicine, ‡Department of Medical-Surgical Sciences and Biotechnologies, Faculty of Pharmacy and Medicine, University of Rome "Sapienza", ICOT Hospital Latina; and §Radiotherapy Unit, San Camillo Forlanini Hospital, Rome, Italy.

Objective: The aim of the study was to assess the diagnostic value of computed tomography perfusion (CTp) of prostate in distinguishing between normal tissue and malignant lesion by using quantitative threshold values of CTp parameters.

Materials And Methods: Sixty-one consecutive men with indication for radical prostatectomy were prospectively enrolled. All patients were intravenously injected with 80-mL bolus of nonionic iodinated contrast medium during cine-mode acquisition protocol. Perfusion data sets were analyzed by a dedicated software system and values for each of the 4 CTp parameters (blood volume, blood flow, mean transit time, and permeability surface-area product measurements) were recorded. Receiver operating characteristic curves were calculated to find which CTp parameter and which cutoff value might reveal the best diagnostic accuracy. Histopathology was used as reference standard.

Results: Statistical correlation between radiological and pathological results was performed on 48 patients using 3456 segmented squares. Blood volume and permeability surface revealed the best diagnostic accuracy for differentiating between malignant and benign squares, with cutoff values of 6.1 and 16.5, respectively, and a sensitivity of 84.8% and 81.8%, respectively. All parameters showed also a high negative predictive value: 97.1% for blood volume and 95.4% for permeability surface.

Conclusions: Blood volume and permeability surface are the 2 CTp parameters with the highest diagnostic accuracy in differentiating between normal tissue and prostatic neoplasia. Due to the extremely high negative predictive value, they are particularly valuable in excluding the presence of cancer and thus resulting potentially useful in assessing cancer response to adjuvant therapy.
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http://dx.doi.org/10.1097/RCT.0000000000000432DOI Listing
January 2017

Oncogenic MicroRNAs Characterization in Clear Cell Renal Cell Carcinoma.

Int J Mol Sci 2015 Dec 8;16(12):29219-25. Epub 2015 Dec 8.

Department of Anatomical, Histological, Forensic & Orthopaedic Sciences, Section of Histology & Medical Embryology, Sapienza University of Rome, Rome 00161, Italy.

A key challenge for the improvement of clear cell renal cell carcinoma (ccRCC) management could derive from a deeper characterization of the biology of these neoplasms that could greatly improve the diagnosis, prognosis and treatment choice. The aim of this study was to identify specific miRNAs that are deregulated in tumor vs. normal kidney tissues and that could impact on the biology of ccRCC. To this end we selected four miRNAs (miR-21-5p, miR-210-3p, miR-185-5p and miR-221-3p) and their expression has been evaluated in a retrospective cohort of formalin-fixed paraffin-embedded (FFPE) tissues from 20 ccRCC patients who underwent surgical nephrectomy resection. miR-21-5p and miR-210-3p resulted the most significantly up-regulated miRNAs in this patient cohort, highlighting these onco-miRNAs as possible relevant players involved in ccRCC tumorigenesis. Thus, this study reports the identification of specific oncogenic miRNAs that are altered in ccRCC tissues and suggests that they might be useful biomarkers in ccRCC management.
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http://dx.doi.org/10.3390/ijms161226160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4691105PMC
December 2015

A novel combination of triple metachronous malignancies of the kidney, oropharynx and prostate: A case report.

Oncol Lett 2015 Aug 3;10(2):917-920. Epub 2015 Jun 3.

Urology Unit, ICOT, Department of Medico‑Surgical Sciences and Biotechnologies, Faculty of Pharmacy and Medicine, Sapienza University of Rome, Latina 04100, Italy.

Synchronous or metachronous malignancies are a rare event, with an incidence rate that increases with age. The present study reports the case of a 70-year-old Caucasian male who was referred to the outpatient office of the Urology Unit, Sapienza University of Rome (Latina, Italy) due to lower urinary tract symptoms. An abdominal ultrasound investigation was performed that demonstrated the presence of a right renal mass. The patient underwent right radical nephrectomy, which resulted in the definitive diagnosis of clear cell type renal cell carcinoma. The patient was eventually diagnosed with triple primary metachronous cancer consisting of renal clear cell carcinoma, prostate adenocarcinoma and squamous cell carcinoma of the oropharynx (palatine tonsil). To the best of our knowledge, this combination of primary neoplasms has not previously been documented.
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http://dx.doi.org/10.3892/ol.2015.3312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4509434PMC
August 2015

A case report of a rare intramuscular granular cell tumor.

Diagn Pathol 2015 Sep 17;10:162. Epub 2015 Sep 17.

Department of Medico-Surgical Sciences and Biotechnologies, Histology Unit, Sapienza University of Rome, ICOT Hospital, Latina, Italy.

Background: Granular cell tumors (GCTs) were firstly described by Weber in 1854 and 70 years later by Abrikossoff and classified as benign tumors. Originally considered muscle tumors, they have been identified as neural lesions, due to their close association with nerve and to their immunohystochemical characteristics. GCTs are uncommon tumors and they may arise in any part of the body; they have been mainly observed in tongue, chest wall and upper extremities; less frequent sites are larynx, gastrointestinal tract, breast, pituitary stalk and the female anogenital region. Here we report a case of GCT showing an uncommon localization such as the upper third of the right rectus muscle of the abdominal wall.

Case Presentation: A 45 year-old woman of Caucasian origin presented to the surgeon with a 6-month history of light pain in the upper third of the abdominal wall. Radiological exams (Ultrasonography, Computed Tomography and Contrast magnetic resonance imaging) showed a localized in the right rectus abdominis muscle. After excision, histological and immunohystochemical analysis, with the support of electron microscopy, allowed making diagnosis of granular cell tumor.

Discussion: After fist description by Abrikosoff in 1926 of GCT like mesenchymal tumor of unknown origin, in recent years immunohystochemical techniques definitely demonstrated the histogenetic derivation of GCT from Schwann cells. Granular cell tumors are rare, small, slow-growing, solitary and painless subcutaneous nodules which behave in a benign fashion, but can have a tendency to recur; in rare cases they can metastasize, when they became malignant; there are some clinical and histological criteria to suspect the malignance of this tumor.

Conclusion: It is important that clinicians, radiologists and pathologists are aware of the clinical presentation and histopathology of GCT for appropriate management, counselling and follow-up. In our case we had a complete radiological, morphological and immunohystochemical characterization of the lesion and a definitive diagnosis of benignity confirmed by electron microscopy.
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http://dx.doi.org/10.1186/s13000-015-0390-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4573292PMC
September 2015

The role of tendon and subacromial bursa in rotator cuff tear pain: a clinical and histopathological study.

Knee Surg Sports Traumatol Arthrosc 2016 Dec 24;24(12):3779-3786. Epub 2015 May 24.

Istituto Clinico Humanitas IRCSS, Rozzano, MI, Italy.

Purpose: To evaluate a possible association of shoulder pain with the clinical features and the histopathological changes occurring in the ruptured tendon and subacromial bursa of patients with rotator cuff tear.

Methods: One hundred and eighty patients were clinically evaluated with the constant score and the visual analogue pain scale. Radiographs and MRI were performed. The chronology of the rupture, the muscle fatty degeneration according to Goutallier's scale and the tear size were evaluated. For each patient, a biopsy of the supraspinatus tendon and subacromial bursa was performed during arthroscopic rotator cuff tear repair and the specimens were histopathologically analysed.

Results: Clinically, the shoulder was more painful in females, in the presence of a chronic cuff lesion and a low Goutallier's grade (P < 0.05). No association was found between pain and age of the patient and between pain and tear size. Histologically, hypertrophy and inflammation of the tendon and hypertrophy, inflammation, oedema and necrosis of the subacromial bursa were directly associated with pain (P < 0.05). Pain decreased significantly in the presence of fatty metaplasia and necrosis of the tendon (P < 0.05).

Conclusions: This study defines the main clinical and histopathological features of painful rotator cuff tear. In particular, a greater association of pain was observed with the histopathological changes in the bursa compared with those in the rotator cuff. Considering that the bursa plays also an essential role during the healing process, this "new" role of the subacromial bursa as pain generator has important repercussions in both pharmacological and surgical treatments of rotator cuff tears.

Level Of Evidence: IV.
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http://dx.doi.org/10.1007/s00167-015-3650-4DOI Listing
December 2016

Parathyroid Reimplantation in Forearm Subcutaneous Tissue During Thyroidectomy: A Simple and Effective Way to Avoid Hypoparathyroidism.

World J Surg 2015 Aug;39(8):1936-42

Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Corso della Repubblica 79, 04100, Latina, LT, Italy,

Introduction: Parathyroid autotransplantation plays an important role in preventing hypoparathyroidism following thyroidectomy. The preferred reimplantation site is still the sternocleidomastoid muscle, but this approach does not permit to check graft vitality postoperatively. The authors report the first prospective evaluation of normal parathyroid gland reimplantation in forearm subcutaneous tissue (using the same technique proposed during parathyroidectomy for hyperplasia) in case of devascularized or inadvertently removed glands during thyroid surgery.

Materials And Methods: From January 2013 to August 2014, we performed 348 consecutive thyroidectomies for various disease, both benign and malignant. In 25 cases, due to inadvertent parathyroid removal or evidence of insufficient blood supply, we removed and fragmented the gland into 0.5-1 mm slices (one for frozen section) and reimplanted it into two subcutaneous pockets on the non-dominant forearm. After surgery we checked grafted gland function by evaluation of serum parathormone gradient between reimplanted versus non-reimplanted arm (considering significant a ratio of 1.5 or more), at 1 week, 1 and 3 months after surgery.

Results: We observed recovery of reimplanted graft function in 48, 88 and 96% of patients respectively at 1 week, 1 and 3 months after surgery. All patients showed normal parathormone levels in peripheral blood (non-reimplanted arm). In one case we observed post-operative wound hematoma on graft-site. This patient showed no graft functionality in post-operative period (even at 3 months follow-up).

Conclusions: Parathyroid gland reimplantation in forearm subcutaneous tissue during thyroid surgery is a safe, easy and effective procedure; furthermore, it allows a good control of graft functionality and would allow an easy grafted gland removal if needed.
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http://dx.doi.org/10.1007/s00268-015-3070-0DOI Listing
August 2015
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