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Background. Anal HPV infection, anal dysplasia and, ultimately, anal cancer are particularly common in HIV-infected men who have sex with men. Treatment of anal dysplasia, aiming to prevent evolution to squamous cell carcinoma of the anus, is currently limited to direct ablation and/or application of topical therapy. The aim of the present study is to investigate the effect of oral bacteriotherapy (Vivomixx® in EU, Visbiome® in USA) on anal HPV infection and HPV-related dysplasia of the anal canal in HIV-infected men who have sex with men. Methods. In this randomized, placebo-controlled, quadruple-blinded trial (NCT04099433), HIV-positive men who have sex with men with anal HPV infection and HPV-related dysplasia were randomized to receive oral bacteriotherapy or placebo for 6 months. Anal HPV test, anal cytology and high resolution anoscopy with biopsies of anal lesions were performed at baseline and at the end of the study. Safety and tolerability of oral bacteriotherapy were also evaluated. Interim analysis results were presented. Results. 20 participants concluded the study procedures to date. No serious adverse events were reported. In respect to participants randomized to placebo, individuals in the experimental arm showed higher rate of anal dysplasia regression (p = 0.002), lower rate of onset of new anal dysplasia (p = 0.023) and lower rates of worsening of persistent lesions (p = 0.004). Clearance of anal HPV infection was more frequently observed in the bacteriotherapy group (p = 0.067). Conclusion. Being an interim analysis, we limit ourselves to report the preliminary results of the current study. We refer the conclusions relating to the possible effectiveness of the intervention to the analysis of the definitive data.

The transcription factors involved in epithelial–mesenchymal transition (EMT-TFs) silence the genes expressed in epithelial cells (e.g., E-cadherin) while inducing those typical of mesenchymal cells (e.g., vimentin). The core set of EMT-TFs comprises Zeb1, Zeb2, Snail1, Snail2, and Twist1. To date, information concerning their expression profile and clinical utility during thyroid cancer (TC) progression is still incomplete. We evaluated the EMT-TF, E-cadherin, and vimentin mRNA levels in 95 papillary TC (PTC) and 12 anaplastic TC (ATC) tissues and correlated them with patients’ clinicopathological parameters. Afterwards, we corroborated our findings by analyzing the data provided by a case study of the TGCA network. Compared with normal tissues, the expression of E-cadherin was found reduced in PTC and more strongly in ATC, while the vimentin expression did not vary. Among the EMT-TFs analyzed, Twist1 seems to exert a prominent role in EMT, being significantly associated with a number of PTC high-risk clinicopathological features and upregulated in ATC. Nonetheless, in the multivariate analysis, none of the EMT-TFs displayed a prognostic value. These data suggest that TC progression is characterized by an incomplete EMT and that Twist1 may represent a valuable therapeutic target warranting further investigation for the treatment of more aggressive thyroid cancers.

The new Italian cytological classification (2014) of thyroid nodules replaced the TIR3 category of the old classification (2007) with two subclasses, TIR3A and TIR3B, with the aim of reducing the rate of surgery for benign diseases. Moreover, thyroid imaging reporting and data system (TI-RADS) score appears to ameliorate the stratification of the malignancy risk. We evaluated whether the new Italian classification has improved diagnostic accuracy and whether its association with TI-RADS score could improve malignancy prediction. We retrospectively analyzed 70 nodules from 70 patients classified as TIR3 according to the old Italian classification who underwent surgery for histological diagnosis. Of these, 51 were available for cytological revision according to the new Italian cytological classification. Risk of malignancy was determined for TIR3A and TIR3B, TI-RADS score, and their combination. A different rate of malignancy (p=0.0286) between TIR3A (13.04%) and TIR3B (44.44%) was observed. Also TI-RADS score is significantly (p=0.003) associated with malignancy. By combining cytology and TI-RADS score, patients could be divided into three groups with low (8.3%), intermediate (21.4%), and high (80%) risk of malignancy. In conclusion, the new Italian cytological classification has an improved diagnostic accuracy. Interestingly, the combination of cytology and TI-RADS score offers a better stratification of the malignancy risk.

Thyroid disease and hyperparathyroidism are the most common endocrine disorders. The incidence of thyroid disease in patients with hyperparathyroidism ranges in the different series from 17 to 84%, and thyroid cancer occurs with an incidence ranging from 2 to 15%. The aim of our study was to analyze the management of elderly patients with concomitant thyroid and parathyroid disease in order to define the best surgical therapeutic strategy and avoid reoperations associated with a higher risk of complications. All consecutive patients (64 patients, age range 60–75 years), undergoing surgery for hyperparathyroidism, from January 2011 to June 2014, were retrospectively evaluated. Enrolled patients were divided into two study groups of patients affected by hyperparathyroidism with or without a concomitant thyroid disease. Out of 64 patients enrolled in our study (24 men, age range 60–75 years), affected by hyperparathyroidism, 34 had an associated thyroid disease and were treated with total thyroidectomy and parathyroidectomy. The group, who underwent parathyroidectomy associated with thyroidectomy, had no greater complications than the group receiving only parathyroidectomy. Thyroid disease must be excluded in patients affected by hyperparathyroidism. It is difficult to determine whether hyperparathyroidism can be considered a risk factor for thyroid disease, but an accurate preoperative study is essential for a surgery able to treat both thyroid and parathyroid disease. In this way, we avoid the elderly patient, with associated morbidity and increased surgical risk, to undergo a reoperation for thyroid disease, burdened with major complications.

Epithelial thyroid cancers (TC) comprise two differentiated histotypes (DTC), the papillary (PTC) and the follicular (FTC) thyroid carcinomas which, following dedifferentiation, are assumed to give rise to the poorly differentiated thyroid carcinomas and the rare, but highly aggressive and invariably fatal, anaplastic thyroid carcinomas. Although thyroid cancer mortality has not been changed, its annual incidence has increased over the last two decades, mainly because of the improved ability to diagnose malignant transformation in small non-palpable thyroid nodules. Despite DTC patients have a favorable prognosis, aggressive disease is more frequently observed in the elderly showing a higher disease-specific mortality. Of relevance is the high prevalence of nodular thyroid disease in aged patients being higher than 90%, in women older than 60 year, and 60% in men older than 80 year. This implies a careful evaluation of thyroid nodules in this group of patients in order to exclude malignancy. In fact, despite the tremendous progress in the comprehension of the underlying molecular mechanisms deregulated in DTC progression, several aspects of their clinical management remain to be solved and novel diagnostic strategies are sorely needed. Here, we will attempt to review new molecular approaches, which are currently being exploited in order to ameliorate the diagnosis of thyroid nodules.

The skin is the largest organ of the body, at the boundary with the outside environment. Primarily, it provides a physical and chemical barrier against external insults, but it can act also as immune organ because it contains a whole host of immune-competent cells of both the innate and the adaptive immune systems, which cooperate in eliminating invading pathogens following tissue injury. On the other hand, improper skin immune responses lead to autoimmune skin diseases (AISD), such as pemphigus, bullous pemphigoid, vitiligo, and alopecia. Although the interplay among genetic, epigenetic, and environmental factors has been shown to play a major role in AISD etiology and progression, the molecular mechanisms underlying disease development are far from being fully elucidated. In this context, epidemiological studies aimed at defining the association of different AISD with other autoimmune pathologies revealed possible shared molecular mechanism(s) responsible for disease progression. In particular, over the last decades, a number of reports have highlighted a significant association between thyroid diseases (TD), mainly autoimmune ones (AITD), and AISD. Here, we will recapitulate the epidemiology, clinical manifestations, and pathogenesis of the main AISD, and we will summarize the epidemiological evidence showing the associations with TD as well as possible molecular mechanism(s) underlying TD and AISD pathological manifestations.

Obesity represents a major under-recognized preventable risk factor for cancer development and recurrence, including breast cancer (BC). Healthy diet and correct lifestyle play crucial role for the treatment of obesity and for the prevention of BC. Obesity is significantly prevalent in western countries and it contributes to almost 50% of BC in older women. Mechanisms underlying obesity, such as inflammation and insulin resistance, are also involved in BC development. Fatty acids are among the most extensively studied dietary factors, whose changes appear to be closely related with BC risk. Alterations of specific ω-3 polyunsaturated fatty acids (PUFAs), particularly low basal docosahexaenoic acid (DHA) levels, appear to be important in increasing cancer risk and its relapse, influencing its progression and prognosis and affecting the response to treatments. On the other hand, DHA supplementation increases the response to anticancer therapies and reduces the undesired side effects of anticancer therapies. Experimental and clinical evidence shows that higher fish consumption or intake of DHA reduces BC cell growth and its relapse risk. Controversy exists on the potential anticancer effects of marine ω-3 PUFAs and especially DHA, and larger clinical trials appear mandatory to clarify these aspects. The present review article is aimed at exploring the capacity of DHA in controlling obesity-related inflammation and in reducing insulin resistance in BC development, progression, and response to therapies.

OBJECTIVES: Oesophageal leiomyoma is the most common benign tumour of the oesophagus. The incidence of leiomyomas larger than 10 cm, defined as giant oesophageal leiomyomas (GELs), has been reported in 17% of all cases. Although computed tomographic scan and endoscopy are usually useful for diagnosis, big and symptomatic masses located in the lower mediastinum remain both a diagnostic and therapeutic challenge. METHODS: We describe our experience in the management of 7 patients (4 males and 3 females, with a mean age of 41 years) with GEL treated in our department. Radical resection was performed in all cases with partial oesophagectomy in order to relieve symptoms and to obtain a definitive diagnosis. RESULTS: There was no perioperative mortality. The minimum diameter of the tumours was 15 cm and the maximum was 30 cm. Definitive histological examination confirmed the diagnosis of leiomyoma in all cases without any sign of malignancy. No major postoperative complications developed. Minor complications included partial abdominal wound dehiscence in 1 case, and retention of secretions requiring bronchoscopy in 2. The mean length of hospital stay was 12 days (ranging between 9 and 14 days). After a mean follow-up of 5.4 years (ranging between 12 and 2 years), no sign of recurrence was observed. CONCLUSIONS: Whereas removal of small oesophageal leiomyomas can be performed by simple enucleation by conventional thoracotomy or video-assisted thoracoscopy, partial oesophagectomy is often necessary for giant lesions. Since it is not possible preoperatively to distinguish GEL from leiomyosarcoma when metastases are absent, partial oesophageal resection is not to be considered an overtreatment and radical resection should always be planned. A gastric tube, in our experience employed as an oesophageal substitute, is effective and could reduce the risk of significant postoperative gastro-oesophageal reflux.

About 5% of occult gastrointestinal bleeding derives from small intestinal lesions. The intraoperative enteroscopy (IOE), although the development of double-balloon enteroscopy and capsule endoscopy reduced the indications, is still valid to locate the bleeding site in some selected cases. An 88-year-old woman presenting to the emergency department with a severe anemia underwent the laparotomic exploration and IOE. A 15-mm laparoscopy trocar with a sterile camera drape was adopted to introduce a standard colonoscope through an enterotomy. The operation was safe and effective, without intraoperative morbidity and early complications related to surgery or endoscopy. We propose a technical solution during the IOE to minimize contamination of the surgical field. Although this technique is safe and feasible, further studies are needed to evaluate the method effectiveness.

Haemorrhoidal disease is one of the most common anorectal disorders. The aim of this study is to compare the results, over the last 10 years, of stapled haemorrhoidopexy (SH) with those of standard Milligan–Morgan haemorrhoidectomy (M&M). Furthermore, we discuss the proper indications for each technique in terms of the lowest rate of complications and long-term results. Three hundred forty-three patients with different degrees of symptomatic haemorrhoids underwent SH or M&M from January 2005 to December 2007. Patients were divided into two groups, age and sex matched. The administration of painkillers drugs, antibiotics and laxatives, complication symptoms and hospital stay in all the patients were recorded after surgical treatment. The mean operative time was shorter in the stapled group compared to that in the open group (31 min versus 40 min). Postoperative pain, hospital stay and return to full activity were shorter in the stapled group. There was a significant difference in the wound healing time between the two groups. We noticed a higher rate of recurrence in patients treated with stapled haemorrhoidectomy for fourth-degree haemorrhoids. According to our experience, the Longo technique is indicated for the treatment of haemorrhoids of second- and third degree. In the latter grades of prolapse, the Milligan–Morgan haemorrhoidectomy can also be applied with good outcomes. We believe that, in case of irreducible prolapse, the M&M is to be preferred. However, operative management varies according to surgeon's interest and is tailored to meet the individual patient's need.