Papers by Prof. Valerio D'Orazi
Breast Care, 2017
Breast-oncoplastic surgery, allowing local tumor control and a better cosmetic outcome, is oncolo... more Breast-oncoplastic surgery, allowing local tumor control and a better cosmetic outcome, is oncologically safe when applied to early-stage breast cancer. Breast cancer recurrence following conservative therapy may occur during the first 5 years after treatment, with a peak incidence after 2 years. Therefore, during the follow-up period, patients undergo a series of ultrasound (US) and mammographic examinations. However, after surgery and radiation therapy, several modifications occur in the treated breast, causing difficulties in image interpretation, especially when local recurrence is suspected. Although not included in routine follow-up, magnetic resonance imaging (MRI) is often used in clinical practice, being considered more sensitive than the conventional imaging examinations in discriminating between postsurgical tissue modifications and tumor recurrence. In this review article, we analyze expected and pathologic breast MRI findings after conservative oncoplastic surgery compa...
Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery, 2017
The INI1/SMARCB1 gene protein product has been implicated in the direct pathogenesis of schwannom... more The INI1/SMARCB1 gene protein product has been implicated in the direct pathogenesis of schwannomas from patients with one form of schwannomatosis [SWNTS1; MIM # 162091] showing a mosaic pattern of loss of protein expression by immunohistochemistry [93% in familial vs. 55% in sporadic cases]. To verify whether such INI1/SMARCB1 mosaic pattern could be extended to all schwannomas arising in the sporadic and familial schwannomatoses [i.e. to SMARCB1-related (SWNTS1) or LZTR1-related (SWNTS2) schwannomatosis or to SMARCB1/LZTR1-negative schwannomatosis] and whether it could be involved in classical NF2 or solitary peripheral schwannomas METHODS: We blindly analysed schwannoma samples obtained from a total of 22 patients including (a) 2 patients (2 males; aged 38 and 55 years) affected by non-familial SMARCB1-associated schwannomatosis (SWTNS1); (b) 1 patient (1 female; aged 33 years) affected by familial schwannomatosis (SWTNS1/ SMARCB1 germ line mutations); (c) 5 patients (3 males, 2 ...
In Vivo, 2016
vascularization. Ultrasound-assisted fine-needle aspiration cytology obtained hematic material wh... more vascularization. Ultrasound-assisted fine-needle aspiration cytology obtained hematic material which was not useful in diagnosis. The patient refused any other invasive
Anticancer research, 2016
Breast-conserving surgery (BCS) is considered the gold-standard treatment for early breast cancer... more Breast-conserving surgery (BCS) is considered the gold-standard treatment for early breast cancer. Ultrasound-guided percutaneous biopsy or stereotactic biopsy of a breast lesion allows preoperative histological diagnosis. Various techniques have been proposed for identifying non-palpable breast tumors, but the most popular method is the wire-guided localization (WGL) technique. The aim of this study was to propose an alternative technique for optimizing the WGL procedure, facilitating breast surgery and reducing complications. We performed a prospective study on 40 patients with a single non-palpable breast lesion. For the preoperative localization of mammary lesions, patients were divided randomly into two groups: 20 patients underwent conventional WGL technique and 20 underwent 'optimized' personalized technique. In the group treated with the optimized technique, dislocation of the wire occurred in only 2/20 cases, whereas in those with the conventional technique, disloca...
Journal of Experimental & Clinical Cancer Research, 2015
Background: Primitive sarcoma of the breast is a rare and challenging disease at high risk of rec... more Background: Primitive sarcoma of the breast is a rare and challenging disease at high risk of recurrence and with poor prognosis. There are controversies in the diagnosis and management of such solid tumor due to its rarity and heterogeneity. This sarcoma is poorly responsive to both chemotherapy and radiotherapy, thus, surgery is the first and most important therapeutic approach. However, given the rarity of this type tumor it has not be possible to standardize unique guidelines for the proper surgical strategy to adopt. Here, we performed a retrospective study of new 10 cases of primitive sarcoma of the breast that underwent either mastectomy or a more conservative quadrantectomy, in the attempt to better standardize correct surgical indications. Methods: Ten new cases of primitive sarcoma of the breast were registered between 2002 and 2012 and constituted the study group. They underwent either mastectomy or quadrantectomy and the clinical, prognostic and survival characteristics after surgery were analysed. Results: Within the group of patients treated with mastectomy, two had metastasis and died because of that. Among the five patients treated with quadrantectomy four are alive and free of disease after 3 to 5 years follow-up, while the patient with sarcoma arising in pregnancy, although is still alive, developed lung metastases four years after surgery. Conclusions: The first and most important therapeutic approach to primary sarcomas of the breast is surgical which has the purpose to achieve radical tumor excision to prevent local recurrence and skip metastases. However, given the rarity of the condition and the consequent small number of cases in this, like in similar studies, it is not possible to draw any definitive conclusions and further studies with larger numbers are necessary. However it would appear that performing a larger procedure such as mastectomy rather than performing a more limited one such as a quadrantectomy, has no advantage in terms of overall prognosis.
SpringerPlus, 2015
The hernia of Amyand is an inguinal hernia containing the appendix in the sac. It is a rare patho... more The hernia of Amyand is an inguinal hernia containing the appendix in the sac. It is a rare pathology often diagnosed only intra-operatively. We report a case even more rare of a giant left-sided inguinoscrotal Amyand hernia with appendiceal abscess without clinical findings of incarceration/strangulation, occlusion, perforation, or acute scrotum and with the presence in the sac of the caecum and other anatomical structures (last ileal loops, bladder and omentum). The 68-years-old man patient successfully underwent surgical treatment only through the hernia sac (meshless repair according to Postempski technique).
Il Giornale di chirurgia
Rectourethral fistulas are an uncommon complication of urinary or rectal surgery, trauma, inflamm... more Rectourethral fistulas are an uncommon complication of urinary or rectal surgery, trauma, inflammatory disease, radiation therapy for prostate cancer; they represent an unique challenge for the surgeon. Although closure can occure spontaneously, most cases of acquired rectourethral fistula need surgical repair. Despite a century of surgical experience, no single approach has been universally accepted. We report a case of a rectourethral fistula occurred in a 73 year-old man after a radical retropubic prostatectomy and external beam irradiation for prostate cancer, successfully treated with perineal approach.
![Research paper thumbnail of [Thyroid anaplastic tumor: our experience]](https://a.academia-assets.com/images/blank-paper.jpg)
Chirurgia italiana
We report our experience over the past 10 years in the treatment of thyroid anaplastic carcinoma ... more We report our experience over the past 10 years in the treatment of thyroid anaplastic carcinoma analysing retrospectively 21 cases of surgical treatment (7 total thyroidectomies, 12 partial resection of the tumours and 2 biopsies). We consider the prognosis, which is invariably fatal, with no survival at 19 months and a mean survival of only 9 months, and assess the validity of a combined therapeutic approach (surgery + radiotherapy + chemotherapy) to increase survival and, above all, the patient's quality of life. The importance is stressed of through monitoring of risk factors consisting in concomitant or previous benign or malignant thyroid disease, considering total thyroidectomy to be necessary in principle for any variety of thyroid cancer. Lastly, we examine the survival trend in terms of residual disease and the presence or otherwise of remote metastases.
The Foot, 2014
Plexiform neurofibromas are benign tumors of the peripheral nerve. Diagnosis may be challenging, ... more Plexiform neurofibromas are benign tumors of the peripheral nerve. Diagnosis may be challenging, if they present mimicking other peripheral nerve pathologies. We report the case of a patient who had severe foot pain, which progressively hampered her walking ability, erroneously attributed to recurrent Morton's neuroma. Diagnosis of plexiform neurofibroma of her right medial plantar nerve was made 15 years after the appearance of symptoms. Pain and function recovered after radical neurotomy of the medial plantar nerve. A correct diagnosis is an essential starting point in the treatment of neurofibromas and a misdiagnosis may lead to an inappropriate treatment.
Advances in Bioscience and Biotechnology, 2013
Peripheral nerve injury is a common occurrence and represents a major economic burden for society... more Peripheral nerve injury is a common occurrence and represents a major economic burden for society. The development of novel strategies to enhance peripheral nerve regeneration is, therefore, of great relevance. Conventional treatments include surgical repair of the damaged nerves for minor injuries, whereas autologous nerve grafts are required to recover longer interruptions. However, despite great surgical advances, functional recovery is often poor. Although it is well known that the peripheral nervous system has a greater regenerative capacity than the central nervous system and, considering the scientific advancements and knowledge in regenerative medicine, clinical applications appears still limited. This review provides an overview of the methodological approaches currently under study, aimed at enhancing peripheral nerve regeneration. In particular, tissue engineering, cell therapy and pharmacological approaches will be discussed.
Journal of Experimental & Clinical Cancer Research, 2015
Background: Activation of wild-type p53 in response to genotoxic stress occurs through different ... more Background: Activation of wild-type p53 in response to genotoxic stress occurs through different mechanisms including protein conformation, posttranslational modifications, and nuclear localization, leading to DNA binding to sequence-specific promoters. Zinc ion plays a crucial role in stabilizing p53/DNA binding to induce canonical target genes. Mutant p53 proteins undergo protein misfolding that can be counteracted by zinc. However, whether zinc supplementation might have a beneficial antitumor effect in wild-type p53-carrying cells in combination with drugs, has not been addressed so far. Methods: In this study we compared the effect of two antitumor treatments: on the one hand wild-type p53-carrying colon cancer cells were treated with low and high doses of chemotherapeutic agent Adriamycin and, on the other hand, Adriamycin was used in combination with ZnCl 2. Biochemical and molecular analyses were applied to evaluate p53 activity and biological outcomes in this setting. Finally, the effect of the different combination treatments were applied to assess tumor growth in vivo in tumor xenografts. Results: We found that low-dose Adriamycin did not induce p53 activation in wtp53-carrying colon cancer cells, unless in combination with ZnCl 2. Mechanistically, ZnCl 2 was a key determinant in inducing wtp53/DNA binding and transactivation of target genes in response to low-dose Adriamycin that used alone did not achieve such effects. Finally, in vivo studies, in a model of wtp53 colon cancer xenograft, show that low-dose Adriamycin did not induce tumor regression unless in combination with ZnCl 2 that activated endogenous wtp53. Conclusions: These results provide evidence that ZnCl 2 might be a valuable adjuvant in chemotherapeutic regimens of colorectal cancer harboring wild-type p53, able to both activate p53 and reduce the amount of drugs for antitumor purposes.
International Journal of Oncology, 2015
TP53 mutation is a common event in many cancers, including thyroid carcinoma. Defective p53 activ... more TP53 mutation is a common event in many cancers, including thyroid carcinoma. Defective p53 activity promotes cancer resistance to therapies and a more malignant phenotype, acquiring oncogenic functions. Rescuing the function of mutant p53 (mutp53) protein is an attractive anticancer therapeutic strategy. Zn(II)-curc is a novel small molecule that has been shown to target mutp53 protein in several cancer cells, but its effect in thyroid cancer cells remains unclear. Here, we investigated whether Zn(II)-curc could affect p53 in thyroid cancer cells with both p53 mutation (R273H) and wild-type p53. Zn(II)-curc induced mutp53H273 downregulation and reactivation of wild-type functions, such as binding to canonical target promoters and target gene transactivation. This latter effect was similar to that induced by PRIMA-1. In addition, Zn(II)-curc triggered p53 target gene expression in wild-type p53-carrying cells. In combination treatments, Zn(II)-curc enhanced the antitumor activity of chemotherapeutic drugs, in both mutant and wild-type-carrying cancer cells. Taken together, our data indicate that Zn(II)-curc promotes the reactivation of p53 in thyroid cancer cells, providing in vitro evidence for a potential therapeutic approach in thyroid cancers.
International Journal of Oncology, 2014
Recent studies suggest that gentian violet (GV) may have anticancer activity by inhibiting for in... more Recent studies suggest that gentian violet (GV) may have anticancer activity by inhibiting for instance NADPH oxidases (Nox genes) whose overexpression is linked to tumor progression. Nox1 overexpression has been shown to inhibit transcriptional activity of the oncosuppressor p53, impairing tumor cell response to anticancer drugs. The tumor suppressor p53 is a transcription factor that, upon cellular stress, is activated to induce target genes involved in tumor cell growth inhibition and apoptosis. Thus, its activation is important for efficient tumor eradication. In this study, we examined the effect of GV on wild-type (wt) p53 activity in cancer cells. We found that GV was able to overcome the inhibitory effect of the NADPH oxidase Nox1 on p53 transcriptional activity. For the first time we show that GV was able to directly induce p53/DNA binding and transcriptional activity. In vitro, GV markedly induced cancer cell death and apoptotic marker PARP cleavage in wtp53-carrying cells. GV-induced cell death was partly inhibited in cells deprived of p53, suggesting that the anticancer activity of GV may partly depend on p53 activation. GV is US Food and Drug Administration approved for human use and may, therefore, have therapeutic potential in the management of cancer through p53 activation.
Journal of Experimental & Clinical Cancer Research, 2020
Background: Tumor progression and tumor response to anticancer therapies may be affected by activ... more Background: Tumor progression and tumor response to anticancer therapies may be affected by activation of oncogenic pathways such as the antioxidant one induced by NRF2 (nuclear factor erythroid 2-related factor 2) transcription factor and the pathways modified by deregulation of oncosuppressor p53. Often, oncogenic pathways may crosstalk between them increasing tumor progression and resistance to anticancer therapies. Therefore, understanding that interplay is critical to improve cancer cell response to therapies. In this study we aimed at evaluating NRF2 and p53 in several cancer cell lines carrying different endogenous p53 status, using a novel curcumin compound since curcumin has been shown to target both NRF2 and p53 and have anti-tumor activity. Methods: We performed biochemical and molecular studies by using pharmacologic of genetic inhibition of NRF2 to evaluate the effect of curcumin compound in cancer cell lines of different tumor types bearing wild-type (wt) p53, mutant (mut) p53 or p53 null status. Results: We found that the curcumin compound induced a certain degree of cell death in all tested cancer cell lines, independently of the p53 status. At molecular level, the curcumin compound induced NRF2 activation, mutp53 degradation and/or wtp53 activation. Pharmacologic or genetic NRF2 inhibition further increased the curcumin-induced cell death in both mutp53-and wtp53-carrying cancer cell lines while it did not increase cell death in p53 null cells, suggesting a cytoprotective role for NRF2 and a critical role for functional p53 to achieve an efficient cancer cell response to therapy.
Nutrients, 2021
The present review deals with the functional roles of iodine and its metabolism. The main biologi... more The present review deals with the functional roles of iodine and its metabolism. The main biological function of iodine concerns its role in the biosynthesis of thyroid hormones (THs) by the thyroid gland. In addition, however, further biological roles of iodine have emerged. Precisely, due to its significant action as scavenger of reactive oxygen species (ROS), iodine is thought to represent one of the oldest antioxidants in living organisms. Moreover, iodine oxidation to hypoiodite (IO−) has been shown to possess strong bactericidal as well as antiviral and antifungal activity. Finally, and importantly, iodine has been demonstrated to exert antineoplastic effects in human cancer cell lines. Thus, iodine, through the action of different tissue-specific peroxidases, may serve different evolutionarily conserved physiological functions that, beyond TH biosynthesis, encompass antioxidant activity and defense against pathogens and cancer progression.
Photochemistry and Photobiology, 2019
Clinical Research on Foot & Ankle, 2017
Giornale di Chirurgia - Journal of Surgery, 2016
International journal of surgery (London, England), 2017
The aim of this study was to test two different video cameras and recording systems used in thyro... more The aim of this study was to test two different video cameras and recording systems used in thyroid surgery in our Department. This is meant to be an attempt to record the real point of view of the magnified vision of surgeon, so as to make the viewer aware of the difference with the naked eye vision. In this retrospective study, we recorded and compared twenty thyroidectomies performed using loupes magnification and microsurgical technique: ten were recorded with GoPro(®) 4 Session action cam (commercially available) and ten with our new prototype of head mounted video camera. Settings were selected before surgery for both cameras. The recording time is about from 1 to 2 h for GoPro(®) and from 3 to 5 h for our prototype. The average time of preparation to fit the camera on the surgeon's head and set the functionality is about 5 min for GoPro(®) and 7-8 min for the prototype, mostly due to HDMI wiring cable. Videos recorded with the prototype require no further editing, which i...
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Papers by Prof. Valerio D'Orazi