HIPK2 in Colon Cancer: A Potential Biomarker for Tumor Progression and Response to Therapies.

Colon cancer, one of the most common and fatal cancers worldwide, is characterized by stepwise accumulation of specific genetic alterations in tumor suppressor genes or oncogenes, leading to tumor growth and metastasis. HIPK2 (homeodomain-interacting protein kinase 2) is a serine/threonine protein kinase and a "bona fide" oncosuppressor protein. Its activation inhibits tumor growth mainly by promoting apoptosis, while its inactivation increases tumorigenicity and resistance to therapies of many different cancer types, including colon cancer. HIPK2 interacts with many molecular pathways by means of its kinase activity or transcriptional co-repressor function modulating cell growth and apoptosis, invasion, angiogenesis, inflammation and hypoxia. HIPK2 has been shown to participate in several molecular pathways involved in colon cancer including p53, Wnt/ß-catenin and the newly identified nuclear factor erythroid 2 (NF-E2) p45-related factor 2 (NRF2). HIPK2 also plays a role in tumor-host interaction in the tumor microenvironment (TME) by inducing angiogenesis and cancer-associated fibroblast (CAF) differentiation. The aim of this review is to assess the role of HIPK2 in colon cancer and the underlying molecular pathways for a better understanding of its involvement in colon cancer carcinogenesis and response to therapies, which will likely pave the way for novel colon cancer therapies.

Intraoperative Neuromonitoring and Optical Magnification in the Prevention of Recurrent Laryngeal Nerve Injuries during Total Thyroidectomy.

Background and Objectives: Recurrent laryngeal nerve (RLN) paralysis is a fearful complication during thyroidectomy. Intraoperative neuromonitoring (IONM) and optical magnification (OM) facilitate RLN identification and dissection. The purpose of our study was to evaluate the influence of the two techniques on the incidence of RLN paralysis and determine correlations regarding common outcomes in thyroid surgery. Materials and Methods: Two equally sized groups of 50 patients who underwent total thyroidectomies were examined. In the first group (OM), only surgical binocular loupes (2.5×−4.5×) were used during surgery, while in the second group (IONM), the intermittent NIM was applied. Results: Both the operative time and the length of hospitalization were shorter in the OM group than in the IONM group (median 80 versus 100 min and median 2 versus 4 days, respectively) (p < 0.05). The male patients were found to have a five-fold higher risk of developing transient dysphonia than the females (adjusted OR 5.19, 95% IC 0.99−27.18, p = 0.05). The OM group reported a four-fold higher risk of developing transient hypocalcemia than the IONM group (OR 3.78, adjusted OR 4.11, p = 0.01). Despite two cases of temporary bilateral RLN paralysis in the IONM group versus none in the OM group, no statistically significant difference was found (p > 0.05). No permanent RLN paralysis or hypoparathyroidism have been reported. Conclusions: Despite some limitations, our study is the first to compare the use of IONM with OM alone in the prevention of RLN injuries. The risk of recurrent complications remains comparable and both techniques can be considered valid instruments, especially if applied simultaneously by surgeons.

May predictors of difficulty in thyroid surgery increase the incidence of complications? Prospective study with the proposal of a preoperative score.

BACKGROUND: Although thyroidectomy is one of the most common surgical procedures performed worldwide, some permanent complications, despite the considerably reducing incidence, may affect dramatically the patients quality of life. The purpose of this study is to evaluate whether factors identified preoperatively and expressed in a score could be predictors of major surgical difficulty during total thyroidectomy and influence the incidence of complications. METHODS: A total of 164 patients who underwent total thyroidectomy were examined. For each patient we calculated a preoperative score, including seven parameters, which we evaluated to be predictors of difficulty in thyroid surgery, that is, sex, body mass index (BMI), neck length, neck extension, thyroid gland volume, thyroiditis, and increased parenchymal vascularization. The overall score was also compared with peri- and post-operative factors describing objectively the difficulty in thyroid surgery. These factors are the duration of the operation, the length of hospitalization, the incidence of complications such as hemorrhage, hypoparathyroidism, and recurrent laryngeal nerve injuries. RESULTS: There was no statistically significant association between our score and either the percentage of postoperative complications or the length of hospitalization. The operative time was the only variable remarkably associated with the score value (p < 0.00001). Comparing the duration of the operation with each of the preoperative predictive factors, we found that none of the factors reached the value of statistical significance, but a close association could be noted with the thyroid volume and the BMI. CONCLUSIONS: In our study, predictors of difficulty in thyroidectomy did not affect morbidity rates, as suggested by previous studies, but only operative times, which were significantly increased in patients with higher score. Although our results have limited statistical significance, they allow us to confirm the fundamental role of a systematic use of optical magnification and microsurgical technique in thyroidectomy. Further studies, with a larger cohort of patients, are needed to validate our results and to formulate a universally accepted predictive score of difficulty in thyroidectomy preoperatively.

A mosaic pattern of INI1/SMARCB1 protein expression distinguishes Schwannomatosis and NF2-associated peripheral schwannomas from solitary peripheral schwannomas and NF2-associated vestibular schwannomas.

BACKGROUND: 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]. AIM OF STUDY: 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 females; aged 33 to 35 years) affected by non-familial (sporadic) LZTR1-associated schwannomatosis (SWNTS2); (d) 3 patients (3 males; aged 35 to 47 years) affected by familial schwannomatosis (SWTNS2/ LZTR1 germ line mutations); (e) 2 patients (1 male, 1 female; aged 63 and 49 years, respectively) affected by non-familial schwannomatosis (SWTNS, negative for SMARCB1, LZTR1 and NF2 gene mutations); (f) 4 patients (3 males, 1 females; aged 15 to 24 years) affected by classical NF2 (NF2: harbouring NF2 germ line mutations; and (g) 5 patients (3 males, 2 females; aged 33 to 68 years) who had solitary schwannomas. [follow-up = 15-30 years; negative for constitutional/somatic mutation analysis for the SMARCB1, LZTR1 and NF2 genes] were (blindly) analyzed. The INI1/SMARCB1 immunostaining pattern was regarded as (1) diffuse positive nuclear staining [= retained expression] or (2) mosaic pattern [mixed positive/negative nuclei = loss of expression in a subset of tumour cells]. RESULTS: All solitary peripheral schwannomas and NF2-associated vestibular schwannomas showed diffuse nuclear INI1/SMARCB1 staining in 97-100% of neoplastic cells; schwannomas obtained from all cases of non-familial and familial schwannomatosis and NF2-associated non-vestibular schwannomas showed a mosaic pattern ranging from 10 to 70% of INI1/SMARCB1-positive expression. We did not record a complete lack of nuclear staining. CONCLUSIONS: The present data suggests that (a) mosaic loss of immunohistochemical INI1/SMARCB1 expression, despite the interlesional variability, is a reliable marker of schwannomatosis regardless of the involved gene and it might help in the differential diagnosis of schwannomatosis vs. solitary schwannomas and (b) INI1/SMARCB1 expression is not useful in the differential with mosaic NF2, since NF2-associated peripheral schwannomas show the same immunohistochemical pattern.

Spinal neurofibromatosis with central nervous system involvement in a set of twin girls and a boy: further expansion of the phenotype.

BACKGROUND: Familial spinal neurofibromatosis is a form of neurofibromatosis 1 (NF1), consisting of extensive, symmetrical, histologically proven, multiple neurofibromas of the spinal roots at every level and of all major peripheral nerves sometimes associated with typical NF1 stigmata; most cases underlie NF1 gene mutations. OBJECTIVES: The objectives of this study are (1) to report the findings in a set of 16-year-old monozygotic twin girls and a 14-year-old boy and (2) to review the existing literature. METHODS AND RESULTS: In this article, we report the cases of three children who (1) had manifested mildly different symptomatic neuropathy (twins, aged 4 years; and a boy, aged 9 years) associated with massive, symmetrical neurofibromas; (2) had few café-au-lait spots with irregular margins and pale brown pigmentation; (3) were presented with, at brain magnetic resonance imaging (MRI), bilateral, NF1-like high-signal abnormalities in the basal ganglia; (4) yielded missense NF1 gene mutations in exon 39; and (5) had unaffected parents with negative NF1 genetic testing as well as discuss 12 families and 20 sporadic and 5 additional cases that presented spinal neurofibromatosis within classical NF1 families (53 cases) that were reported in the literature. CONCLUSIONS: This article presents the first report on (1) spinal neurofibromatosis in a set of affected monozygotic twins; (2) the earliest onset of the disease; and (3) the occurrence of high signal lesions in the brain at MRI.

HIPK2 in Angiogenesis: A Promising Biomarker in Cancer Progression and in Angiogenic Diseases.

Angiogenesis is the formation of new blood capillaries taking place from preexisting functional vessels, a process that allows cells to cope with shortage of nutrients and low oxygen availability. Angiogenesis may be activated in several pathological diseases, from tumor growth and metastases formation to ischemic and inflammatory diseases. New insights into the mechanisms that regulate angiogenesis have been discovered in the last years, leading to the discovery of new therapeutic opportunities. However, in the case of cancer, their success may be limited by the occurrence of drug resistance, meaning that the road to optimize such treatments is still long. Homeodomain-interacting protein kinase 2 (HIPK2), a multifaceted protein that regulates different molecular pathways, is involved in the negative regulation of cancer growth, and may be considered a "bona fide" oncosuppressor molecule. In this review, we will discuss the emerging link between HIPK2 and angiogenesis and how the control of angiogenesis by HIPK2 impinges in the pathogenesis of several diseases, including cancer.

The Sweet Side of HIPK2.

HIPK2 is an evolutionary conserved protein kinase which modulates many molecular pathways involved in cellular functions such as apoptosis, DNA damage response, protein stability, and protein transcription. HIPK2 plays a key role in the cancer cell response to cytotoxic drugs as its deregulation impairs drug-induced cancer cell death. HIPK2 has also been involved in regulating fibrosis, angiogenesis, and neurological diseases. Recently, hyperglycemia was found to positively and/or negatively regulate HIPK2 activity, affecting not only cancer cell response to chemotherapy but also the progression of some diabetes complications. The present review will discuss how HIPK2 may be influenced by the high glucose (HG) metabolic condition and the consequences of such regulation in medical conditions.

NGF and BDNF in pediatrics syndromes.

Neurotrophins (NTs) as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) play multiple roles in different settings including neuronal development, function and survival in both the peripheral and the central nervous systems from early stages. This report aims to provide a summary and subsequent review of evidences on the role of NTs in rare and non-common pediatric human diseases associated with changes in neurodevelopment. A variety of diseases has been analyzed and many have been linked to NTs neurobiological effects, including chronic granulomatous disease, hereditary sensory and autonomic neuropathy, Duchenne muscular dystrophy, Bardet-Biedl syndrome, Angelman syndrome, fragile X syndrome, trisomy 16, Williams-Beuren syndrome, Prader-Willi syndrome, WAGR syndrome, fetal alcohol spectrum disorders, Down syndrome and Klinefelter Syndrome. NTs alterations have been associated with numerous pathologic manifestations including cognitive defects, behavioral abnormalities, epilepsy, obesity, tumorigenesis as well as muscle-skeletal, immunity, bowel, pain sensibility and cilia diseases. In this report, we discuss that further studies are needed to clear a possible therapeutic role of NTs in these still often uncurable diseases.

Insights on the Association between Thyroid Diseases and Colorectal Cancer.

Benign and malignant thyroid diseases (TDs) have been associated with the occurrence of extrathyroidal malignancies (EMs), including colorectal cancers (CRCs). Such associations have generated a major interest, as their characterization may provide useful clues regarding diseases' etiology and/or progression, with the possible identification of shared congenital and environmental elements. On the other hand, elucidation of the underlying molecular mechanism(s) could lead to an improved and tailored clinical management of these patients and stimulate an increased surveillance of TD patients at higher threat of developing EMs. Here, we will examine the epidemiological, clinical, and molecular findings connecting TD and CRC, with the aim to identify possible molecular mechanism(s) responsible for such diseases' relationship.

Effect of the COVID-19 pandemic on surgery for indeterminate thyroid nodules (THYCOVID): a retrospective, international, multicentre, cross-sectional study.

BACKGROUND: Since its outbreak in early 2020, the COVID-19 pandemic has diverted resources from non-urgent and elective procedures, leading to diagnosis and treatment delays, with an increased number of neoplasms at advanced stages worldwide. The aims of this study were to quantify the reduction in surgical activity for indeterminate thyroid nodules during the COVID-19 pandemic; and to evaluate whether delays in surgery led to an increased occurrence of aggressive tumours. METHODS: In this retrospective, international, cross-sectional study, centres were invited to participate in June 22, 2022; each centre joining the study was asked to provide data from medical records on all surgical thyroidectomies consecutively performed from Jan 1, 2019, to Dec 31, 2021. Patients with indeterminate thyroid nodules were divided into three groups according to when they underwent surgery: from Jan 1, 2019, to Feb 29, 2020 (global prepandemic phase), from March 1, 2020, to May 31, 2021 (pandemic escalation phase), and from June 1 to Dec 31, 2021 (pandemic decrease phase). The main outcomes were, for each phase, the number of surgeries for indeterminate thyroid nodules, and in patients with a postoperative diagnosis of thyroid cancers, the occurrence of tumours larger than 10 mm, extrathyroidal extension, lymph node metastases, vascular invasion, distant metastases, and tumours at high risk of structural disease recurrence. Univariate analysis was used to compare the probability of aggressive thyroid features between the first and third study phases. The study was registered on ClinicalTrials.gov, NCT05178186. FINDINGS: Data from 157 centres (n=49 countries) on 87 467 patients who underwent surgery for benign and malignant thyroid disease were collected, of whom 22 974 patients (18 052 [78·6%] female patients and 4922 [21·4%] male patients) received surgery for indeterminate thyroid nodules. We observed a significant reduction in surgery for indeterminate thyroid nodules during the pandemic escalation phase (median monthly surgeries per centre, 1·4 [IQR 0·6-3·4]) compared with the prepandemic phase (2·0 [0·9-3·7]; p<0·0001) and pandemic decrease phase (2·3 [1·0-5·0]; p<0·0001). Compared with the prepandemic phase, in the pandemic decrease phase we observed an increased occurrence of thyroid tumours larger than 10 mm (2554 [69·0%] of 3704 vs 1515 [71·5%] of 2119; OR 1·1 [95% CI 1·0-1·3]; p=0·042), lymph node metastases (343 [9·3%] vs 264 [12·5%]; OR 1·4 [1·2-1·7]; p=0·0001), and tumours at high risk of structural disease recurrence (203 [5·7%] of 3584 vs 155 [7·7%] of 2006; OR 1·4 [1·1-1·7]; p=0·0039). INTERPRETATION: Our study suggests that the reduction in surgical activity for indeterminate thyroid nodules during the COVID-19 pandemic period could have led to an increased occurrence of aggressive thyroid tumours. However, other compelling hypotheses, including increased selection of patients with aggressive malignancies during this period, should be considered. We suggest that surgery for indeterminate thyroid nodules should no longer be postponed even in future instances of pandemic escalation. FUNDING: None.

The Impact of NRF2 Inhibition on Drug-Induced Colon Cancer Cell Death and p53 Activity: A Pilot Study.

Nuclear factor erythroid 2 (NF-E2) p45-related factor 2 (NRF2) protein is the master regulator of oxidative stress, which is at the basis of various chronic diseases including cancer. Hyperactivation of NRF2 in already established cancers can promote cell proliferation and resistance to therapies, such as in colorectal cancer (CRC), one of the most lethal and prevalent malignancies in industrialized countries with limited patient overall survival due to its escape mechanisms in both chemo- and targeted therapies. In this study, we generated stable NRF2 knockout colon cancer cells (NRF2-Cas9) to investigate the cell response to chemotherapeutic drugs with regard to p53 oncosuppressor, whose inhibition we previously showed to correlate with NRF2 pathway activation. Here, we found that NRF2 activation by sulforaphane (SFN) reduced cisplatin (CDDP)-induced cell death only in NRF2-proficient cells (NRF2-ctr) compared to NRF2-Cas9 cells. Mechanistically, we found that NRF2 activation protected NRF2-ctr cells from the drug-induced DNA damage and the apoptotic function of the unfolded protein response (UPR), in correlation with reduction of p53 activity, effects that were not observed in NRF2-Cas9 cells. Finally, we found that ZnCl2 supplementation rescued the cisplatin cytotoxic effects, as it impaired NRF2 activation, restoring p53 activity. These findings highlight NRF2's key role in neutralizing the cytotoxic effects of chemotherapeutic drugs in correlation with reduced DNA damage and p53 activity. They also suggest that NRF2 inhibition could be a useful strategy for efficient anticancer chemotherapy and support the use of ZnCl2 to inhibit NRF2 pathway in combination therapies.

Prokineticin 2/PROK2 and Male Infertility.

Male infertility represents about 50% of the causes of infertility in couples. The diagnosis process represents an important procedure for defining, when possible, the causes and approaching treatments (pharmacological, surgical) aimed at overcoming the problem. Several scientific studies have set out to discover early and indicative markers capable of providing information on the biological origin of infertility and increase current knowledge in the context of new potential therapeutic approaches. The prokineticin system (PROK) consists of the prokineticin 1 (PROK1) and prokineticin 2 (PROK2) proteins. Through the activation of two G-protein receptors (PROKR1 and PROKR2) regulate a wide range of biological functions, including gastrointestinal motility, circadian rhythm regulation, neurogenesis, angiogenesis, pain perception, and mood regulation. Several studies have highlighted the crucial role of the PROK system in the development and maturation of both male and female human reproductive organs. Particularly in men, the PROK system represents a new system useful to clarify some aspects of testicular pathophysiology and provide new potential hypotheses for therapeutic intervention. This narrative review aims to illustrate the state of the art regarding, in particular, the role of PROK2 in male infertility.

Iodine: Its Role in Thyroid Hormone Biosynthesis and Beyond.

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.

The Glucosamine-derivative NAPA Suppresses MAPK Activation and Restores Collagen Deposition in Human Diploid Fibroblasts Challenged with Environmental Levels of UVB.

The ultraviolet (UV) component of solar radiation is the driving force of life on earth, but it can cause photoaging and skin cancer. In this study, we investigated the effects of the glucosamine-derivative 2-(N-Acetyl)-L-phenylalanylamido-2-deoxy-ß-D-glucose (NAPA) on human primary fibroblasts (FBs) stimulated in vitro with environmental levels of UVB radiation. FBs were irradiated with 0.04 J cm-2 UVB dose, which resulted a mild dosage as shown by the cell viability and ROS production measurement. This environmental UVB dose induced activation of MAP kinase ERK 1/2, the stimulation of c-fos and at lower extent of c-jun, and in turn AP-1-dependent up-regulation of pro-inflammatory factors IL-6 and IL-8 and suppression of collagen type I expression. On the contrary, 0.04 J cm-2 UVB dose was not able to stimulate metalloprotease production. NAPA treatment was able to suppress the up-regulation of IL-6 and IL-8 via the inhibition of MAP kinase ERK phosphorylation and the following AP-1 activation, and was able to attenuate the collagen type I down-regulation induced by the UVBs. Taken together, our results show that NAPA, considering its dual action on suppression of inflammation and stimulation of collagen type I production, represents an interesting candidate as a new photoprotective and photorepairing agents.

A ruthenium(II)-curcumin compound modulates NRF2 expression balancing the cancer cell death/survival outcome according to p53 status.

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. CONCLUSIONS: These findings underline the prosurvival role of curcumin-induced NRF2 expression in cancer cells even when cells underwent mutp53 downregulation and/or wtp53 activation. Thus, NRF2 inhibition increased cell demise particularly in cancer cells carrying p53 either wild-type or mutant suggesting that p53 is crucial for efficient cancer cell death. These results may represent a paradigm for better understanding the cancer cell response to therapies in order to design more efficient combined anticancer therapies targeting both NRF2 and p53.

Reduced chemotherapeutic sensitivity in high glucose condition: implication of antioxidant response.

Resistance to chemotherapy represents a major obstacle to successful treatment. The generation of reactive oxygen species (ROS) has been directly linked to the cytotoxic effects of several antitumor agents, including Adriamycin (ADR), and modulation of the oxidative balance has been implicated in the development and/or regulation of resistance to chemotherapeutic drugs. We recently showed that high glucose (HG) markedly diminished the cancer cell death induced by anticancer agents such as ADR. In the present study we attempted to evaluate the mechanism that impaired the cytotoxic effect of ADR in HG. We found that, in colon cancer cells, HG attenuated ADR-induced ROS production that consequently diminished ADR-induced H2AX phosphorylation and micronuclei (MN) formation. Mechanistically, HG attenuation of ADR-induced ROS production correlated with increased antioxidant response promoted by NRF2 activity. Thus, pharmacologic inhibition of NRF2 pathway by brusatol re-established the ADR cytotoxic effect impaired by HG. Together, the data provide new insights into chemotherapeutic-resistance mechanisms in HG condition dictated by increased NRF2-induced antioxidant response and how they may be overcome in order to restore chemosensitivity and ADR-induced cell death.

Advancement of thyroid surgery video recording: A comparison between two full HD head mounted video cameras.

BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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 is mandatory for videos recorded with GoPro® to highlight the surgical details. CONCLUSION: the present study showed that our prototype of video camera, compared with GoPro® 4 Session, guarantees best results in terms of surgical video recording quality, provides to the viewer the exact perspective of the microsurgeon and shows accurately his magnified view through the loupes in thyroid surgery. These recordings are surgical aids for teaching and education and might be a method of self-analysis of surgical technique.

Plasma Cell Mastitis in Men: A Single-center Experience and Review of the Literature.

Plasma cell mastitis is an inflammatory disease of the breast parenchyma, rare in males. In the last 40 years, few cases have been described in literature. Our recent treatment of male patients affected by plasma cell mastitis raised a series of issues which led us to carry out a critical review of the literature. Plasma cell mastitis is often not well defined and is difficult to assess by clinical examination and radiological investigation alone. An understanding of the pathogenesis and the mechanisms behind plasma cell mastitis may help improve the diagnostic and therapeutic course of the disease, leading to a more targeted and less invasive treatment.

Nipple-sparing Mastectomy in Patients with Preoperative Diagnosis of Non-invasive Breast Carcinoma. A Single-center Experience.

BACKGROUND: Nipple-sparing mastectomy (NSM) is a recognized treatment for selected patients with breast cancer (BC). Our study aimed to analyze 7 years' experience in NSM and breast reconstruction for patients with preoperative diagnosis of non-invasive BC. PATIENTS AND METHODS: All NSMs with breast reconstruction, performed between January 2007 and December 2013 in patients with preoperative diagnosis of non-invasive BC, were considered. RESULTS: Thirty-five NSMs were performed, 23 cases confirming the diagnosis of non-invasive BC, and in 12 patients it also resulted in findings of an invasive component. Patients were stratified into two groups: breast reconstruction was performed i) with silicone definitive implant, ii) with a temporary breast tissue expander. An invasive component at the postoperative histological examination was significantly associated with tissue expander reconstruction (p=0.03). CONCLUSION: In selected cases, NSM is a valid and safe procedure. Further critical evaluations are required for more evidence on this argument.

Oncoplastic central quadrantectomies.

Tumors localized in the central quadrant (centrally located breast tumors) have always represented a challenge for the surgeon because of the critical aesthetical matters related to the nipple-areola complex (NAC). Many years of experience with breast cancer patients treated by using various oncoplastic techniques, has allowed us to develop the modified hemibatwing for the treatment of central breast tumors, where the NAC is involved. Modified hemibatwing-along with the removal of the NAC-is a useful oncoplastic technique and it represents an ideal option for the treatment of central tumors because it assures oncological safety, a reduced surgical timetable and greater aesthetical results.