Rare chondrosarcoma of the breast treated with quadrantectomy instead of mastectomy. A case report

Breast chondrosarcoma is a rare sarcoma that mainly occurs in females >50 years old. To the best of our knowledge, only 16 cases were reported in the literature prior to 2013 and all patients were surgically treated by mastectomy, with or without lymphadenectomy, which was occasionally preceded by neoadjuvant chemotherapy. However, the literature does not report the benefit of mastectomy compared with a more conservative surgery. The present study reports a novel case of extraskeletal chondrosarcoma of the breast. A 63‑year‑old female patient presented with a neoplasm localized in the upper‑outer quadrant of the right breast. The palpable lesion with sharp margins was a firm parenchymatous mass, which was confirmed by ultrasonography and mammography. The patient underwent conservative quadrantectomy instead of mastectomy, followed by post‑surgical chemotherapy. A positron emission tomography scan performed five months subsequent to the surgery revealed no remnants of the disease. The patient underwent a strict clinical and instrumental follow‑up, and two and half years after surgery, there are no signs of recurrent disease. In conclusion, the present case is currently one of the two cases in which a more conservative quadrantectomy was performed, instead of mastectomy. This surgical approach did not lead to metastasis and resulted in a good follow‑up for the patient

Infertility in Fabry’s disease: role of hypoxia and inflammation in determining testicular damage

Fabry’s disease (FD) is a genetic X-linked systemic and progressive rare disease, which is characterized by the accumulation of glycolipid bodies (GB) into the lys- osomes of almost all cell types and consequently by a multiform clinical picture. Here we studied testicular biopsies of a 42 ys old FD patient, presenting infertility with reduced number of spermatozoa and preserved sexual activity. Testicular biopsies have been analyzed by optical microscopy (OM) and transmis- sion electron microscopy (TEM). OM, showed a severe involvement of testis inter- stitium blood vessels with reduced or closed lumen, an increased of connective tis- sue and a substantial thicketing of peritubular region. TEM, showed that GB were abundant in vessel wall cells and in myofibroblast of peritubular region. In contrast with literature reports, Leydig cells were constantly unaffected by GB accumulation showing well preserved ultrastructural organization. On the contrary, tubular cells, although not affected by GB accumulation, appeared severely damaged. These data led us to hypothesize that diffusion of oxygen and nutrients from blood to tubules could be impaired. To test this hypothesis we explored, by immunofluorescence (IF) and molecular biology (MB) coupled to laser capture micro-dissection (LCMD), the activation of HIF/NFkB pathway. IF showed increased signal for HIF1a in all stromal components, while it appeared almost absent in seminipherous tubules. On the contrary, NFkB fluores- cence was evident in tubules. mRNA of tubular and interstitial tissue fractions, separately extracted by LCMD, confirms that HIF1a and hypoxic-related genes such as alarmin recepters (RAGE, TLR4) were overexpressed in the interstitial cells. At the same time, NFkB and a number of proinflammatory genes such as HMOX1, PTGES, SAA1-SAA2 were up- regulated in the tubule microenviroment. Taken together, these results suggest that the GB accumulation in interstitium, reducing vessel lumen and increasing the distance between vessel and tubular cells, leads to chronic progressive hypoxia. Hypoxia has two effects: 1)Necrosis of cells more distant from vessels, especially germinative epithelium and Sertoli cells, releas- ing alarmins; 2)Adaptation to low levels of O2, with activation of HIF1a. In both cas- es a strong activation of NFkB occurs that trigger a inflammatory response (IR). We suggest a role for the IR activation in determining intratubular cells damage and con- sequently, infertility in FD

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

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

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 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

Mastite plasmacellulare nell’uomo: una revisione della letteratura

La mastite plasmacellulare è una patologia molto rara nell’uomo, infatti dal 1974 al 2011 sono stati descritti solo 11 casi. L’esperienza di un paziente maschio affetto da mastite plasma cellulare venuto alla nostra osservazione e l’iter diagnostico terapeutico ci ha stimolato alla presente revisione della letteratura in considerazione della rarità di detta malattia nell’uomo e pertanto delle diverse problematiche diagnostico – terapeutiche ad essa connessa. Va sottolineato che la mastite plasma cellulare, che potrebbe essere interpretata come carcinoma mammario, talvolta può essere la spia di malattie del sistema immunitario come la granulomatosi di Weger, la malattia di Behet, il diabete mellito, e AIDS

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

Abstract 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