Prognosis of Adrenal Oncocytic Neoplasms (AONs): Literature Review of 287 Cases and Presentation of the Oldest Patient.

INTRODUCTION: The adrenocortical oncocytic neoplasms (AONs) are rare tumors of the adrenal gland, classified as oncocytoma (AO), oncocytic neoplasm of uncertain malignant potential (AONUMP) and oncocytic carcinoma (AOC). The aim of this study was to perform a review of the literature, in order to evaluate the prognosis of these rare cancers. We also reported the oldest patient with AON. METHODS: A comprehensive literature review using as key words "adrenal oncocytoma", "adrenal oncocytic neoplasm", and "adrenal oncocytic carcinoma" was performed. REPORT OF THE CASE: We report the case of an 88-year-old woman receiving a left open adrenalectomy for an AON (15 × 10 × 8 cm). The considerable size and weight together with the presence of necrosis were indicative for a lesion with an uncertain potential for malignancy, according to Weiss modified criteria. After two years, the patient was free from any sign of recurrence. RESULTS: Only 287 AONs were detected in the scientific literature, exploring OVID, MEDLINE, PubMed and SCOPUS as dataset. These tumors are usually incidentalomas with an unpredictable malignant potential. Surgical resection remains the mainstay of treatment for AON. CONCLUSION: AO and AONUMP have an excellent prognosis and a low mortality rate, with only three cases of recurrence reported in the literature and one metastatic case four years after first adrenal surgery. In contrast, AOC carries a high risk of local relapses, distant metastasis, and a significantly higher mortality rate (30%). Surgical resection remains the primary treatment for adrenal oncocytic neoplasms.

Evaluation of BRAF, RAS, RET/PTC, and PAX8/PPARg alterations in different Bethesda diagnostic categories: A multicentric prospective study on the validity of the 7-gene panel test in 1172 thyroid FNAs deriving from different hospitals in South Italy.

BACKGROUND: Thyroid fine-needle aspiration (FNA) is a reliable and cost-effective diagnostic tool for establishing the nature of thyroid nodules, although up to 30% of FNAs are still classified as "indeterminate." Molecular testing of FNAs could improve preoperative diagnosis, thereby reducing unnecessary surgery. In this multicenter prospective study the authors investigated, using a 7-gene assay, the distribution and diagnostic impact of BRAF, RAS, RET/PTC, and PAX8/PPARg, the most frequent genomic alterations occurring during thyroid oncogenesis. METHODS: In total, of 1172 routine FNAs from 7 centers in southern Italy were classified according to the Bethesda System for Reporting Thyroid Cytopathology. Each specimen was tested, and molecular data were compared with available histology or cytologic follow-up. RESULTS: In particular, for atypia of undetermined significance/follicular lesion of undetermined significance cases, the 7-gene test confirmed the high positive predictive value of BRAFV600E and BRAF-like mutations (80%) and the moderate positive predictive value of RAS-like alterations (32.4%), suggesting different surgical management, depending on the type of mutation. The rate of mutation-positive FNAs was strictly related to the risk of malignancy of each diagnostic class, supporting the identification of prognostically relevant diagnostic categories. CONCLUSIONS: The 7-gene panel test improves the preoperative risk stratification of indeterminate thyroid FNAs, especially when considering the biologic significance of the different types of mutations. Moreover, the rate of mutation-positive FNAs is related to the risk of malignancy of each diagnostic class.

IBD: Role of intestinal compartments in the mucosal immune response.

BACKGROUND AND AIMS: Laser capture microdissection (LCM) is a powerful tool for the isolation of specific tissue compartments. We aimed to investigate the mucosal immune response that takes place in different intestinal compartments of IBD patients, dissected by LCM, analyzing cytokines expression profile and endoplasmic reticulum (ER) stress markers. METHODS: Frozen sections of gut were obtained from patients with Crohn's disease (CD), ulcerative colitis (UC) and from controls. Using LCM, surface epithelium (SE) and lamina propria (LP) compartments were isolated and total RNA extracted. The relative expression of Th1, Th17 and Treg cytokines was evaluated by quantitative reverse transcriptase real-time PCR (qRT-PCR), in addition to the assessment of mRNA splicing of the transcription factor X-box binding protein-1 (XBP1). Human neutrophil elastase (HNE) and the transcription factor forkhead box P3 (Foxp3) were also analyzed by immunohistochemistry. RESULTS: The increased expression of IL-17 was observed in both intestinal compartments of IBD patients when compared to controls. IFN- γ, TNF-α , IL-10, HNE and Foxp3 were overexpressed in the LP compartment of both IBD patients as compared to controls. An upregulation of IFN-γ and an infiltration of HNE+ cells was found in the SE of patients with UC. Splicing of XBP1 mRNA was recognized in both intestinal compartments of IBD patients when compared to controls. CONCLUSIONS: In IBD patients, both intestinal compartments are involved in Th17 response, whereas, LP compartment plays a prominent role in Th1 and Treg immune responses. Nevertheless, high level of IFN- γ was found in the SE of UC patients, suggesting that this compartment is involved in the Th1 immune response. Our data also suggested that ER stress signalling is active in both LP and SE compartment of IBD patients, thus advocating that ER stress and immunity are intertwined.

Endocrinopathies induced by immune-checkpoint inhibitors in advanced non-small cell lung cancer.

The advent of immunotherapy has recently expanded the therapeutic options in advanced non-small cell lung cancer (NSCLC). In these patients, the recent efficacy demonstration of antibodies against immune checkpoints: the anti-programmed death-1 (PD-1) and anti-programmed death ligand-1 (PD-L1), has led to approval of nivolumab and pembrolizumab (anti-PD-1) in the treatment of advanced NSCLC. The mechanism of action of checkpoint inhibitors explains the development of autoimmune diseases as a side-effect of these medications. Among these, a spectrum of endocrine disorders has been also reported. This manuscript focuses particularly on endocrine disorders induced by immuno-checkpoint inhibitors employed in NSCLC, in order to suggest the strategies for their diagnosis and effective management.

Validation of an extension of the international non-invasive criteria for the diagnosis of hepatocellular carcinoma to the characterization of macroscopic portal vein thrombosis.

BACKGROUND AND AIM: We aimed to validate the non-invasive criteria for the characterization of portal vein thrombosis (PVT) in patients with cirrhosis and hepatocellular carcinoma (HCC). In a prospective study, we examined the impact of arterial hypervascularity, as established by the European Association for the Study of the Liver and the American Association for the Study of Liver Diseases recommendations for the non-invasive diagnosis of HCC, as a criterion for characterizing macroscopic PVT (EASL/AASLD extension criteria). METHODS: A total of 96 cases of PVT detected using ultrasonography in patients with cirrhosis and HCC were included in the study. When coincidental arterial hypervascularity was detected by contrast perfusional ultrasonography and helical computed tomography, the thrombus was considered malignant according to our EASL/AASLD extension criteria. In all cases, an ultrasound-guided biopsy examination of the thrombus was performed. RESULTS: Coincidental hypervascularity was found in 54 of 96 nodules (56.2%), and all were malignant upon biopsy (100% positive predictive value). Twenty-four (25%) had negative results with both techniques (non-vascular thrombus). Biopsies showed HCC in five non-vascular thrombi (5.3% of all thrombi) and in 13 of 18 thrombi with a hypervascularity result from only one technique. CONCLUSIONS: The EASL/AASLD extension criteria for non-invasive diagnosis of malignant thrombosis were satisfied in 75.2% of malignant thrombi; thus, a biopsy is frequently required in this setting. However, in the presence of coincidental hypervascularity of a thrombus with both techniques, a biopsy is not required (absolute positive predictive value for malignancy). Relying on imaging techniques in thrombi could miss the diagnosis of malignant portal invasion in up to 24.9% of cases.

Oxidative stress and steatosis are cofactors of liver injury in primary biliary cirrhosis.

BACKGROUND: Factors responsible for the progression of primary biliary cirrhosis (PBC) are still poorly understood. In the present study, we investigated the associations between the stage of PBC and the immune reaction triggered by oxidative stress; the presence of obesity, steatosis,steatohepatitis; and other toxic, metabolic, or steatogenic factors. METHODS: We studied clinical, laboratory, and histological data for 274 untreated patients with serum antimitochondrial antibody (AMA)-positive PBC. Circulating IgG against human serum albumin adducted with malondialdeyde, the major product of lipid peroxidation, was measured in these patients and in a group of 98 sex-, age and body mass index (BMI)-matched controls. RESULTS: Steatosis was present in 40.5% of all patients. Steatohepatitis was present in 14.9% of all patients. There was a significant association between the frequencies of steatosis and steatohepatitis and the worsening of PBC. Circulating IgG against lipid peroxidation products was significantly higher in the PBC patients than in the controls. Titers of lipid peroxidation-related antibodies were significantly increased in patients with steatosis and inpatients at more advanced stages. Bivariate analysis revealed a significant association between indirect evidence of oxidative stress, steatosis, steatohepatitis, age, BMI, frequency of diabetes, alcohol intake, iron grade after Perl's stain, and PBC stage. Logistic regression analysis confirmed that the titers of antibodies against lipid peroxidation products (odds ratio 4.5, p< .001, 95% confidence interval 3.9­14.4), the presence of steatosis (odds ratio 4.1, 95% confidence interval 2.5­15.4, p< .001), higher BMI (odds ratio 3.9, p< .021, 95%confidence interval 1.4­9.5), and alcohol intake (males ≥ 30 g/day, females ≥ 20 g/day, odds ratio 4.5,95% confidence interval 1.3­19.8, p< .029) were independently associated with more advanced stages of the disease. CONCLUSIONS: The immune reactions triggered by oxidative stress, steatosis, obesity, and alcohol intake are independent predictors of PBC stage progression.

Low-energy interstitial laser photocoagulation for treatment of nonfunctioning thyroid nodules: therapeutic outcome in relation to pretreatment and treatment parameters.

OBJECTIVE: Interstitial laser photocoagulation (ILP) is a recently proposed therapeutic procedure for the ablation of benign thyroid nodules, which has already proven to be safe and effective. However, results supporting the routine use of ILP are still limited. DESIGN: The aim of the study was to evaluate the efficacy and safety of ILP treatment in benign nonfunctioning thyroid nodules and to establish whether the therapeutic outcome may be predicted by any clinical parameter at baseline. Twenty-three patients with either a solitary nodule or a dominant nodule within a multinodular goiter underwent ILP and were evaluated 1 and 3 months later. In order to assess the efficacy of low-energy ILP, the procedure was performed with an output power of 3 W, delivering a mean energy of 33.4 +/- 12.7 Joule/mL of nodule volume, which is much lower than previously reported. MAIN OUTCOME: Nodule volume significantly decreased after ILP as assessed after 1 and 3 months (analysis of variance; F = 5.37; p = 0.007). Patients with multinodular goiter showed a greater reduction at 3 months compared with patients bearing a solitary thyroid nodule (38.6 +/- 5.3 vs. 30.9 +/- 6.5%; p < 0.01). Age, sex, ultrasound pattern (isoechogenous/hypoechogenous), pretreatment volume, number of ILP treatments, and total energy delivered did not show any significant correlation with treatment outcome. CONCLUSIONS: Our results demonstrate that ILP can produce a significant reduction of thyroid nodule volume even when a much lower energy than previously reported is delivered. ILP constitutes a minimally invasive technique, which can be carried out on an outpatient basis and could represent a valid nonsurgical alternative for thyroid nodule management. Dominant nodules within a multinodular goiter appear to be more responsive to ILP compared with solitary thyroid nodules.

Complete response of severe symptomatic bone marrow metastases from heavily pretreated breast cancer with a 3-weekly trastuzumab schedule. A clinical case.

Overexpression of HER-2/neu in breast cancer has been associated with more aggressive disease and poor overall survival. Trastuzumab, a recombinant humanized monoclonal antibody with high affinity for the HER-2 protein, inhibits the growth of breast cancer cells overexpressing HER-2. Trastuzumab showed, as second-line treatment, 15% of objective response in metastatic breast cancer. Bone marrow metastases are detectable in 23% of the patients with advanced breast cancer at first relapse and this rate increases in patients with metastatic disease. We report a case of a complete response of bone marrow metastases from breast cancer using a 3-weekly trastuzumab schedule, in a heavily pretreated patient with severe symptomatic pancytopenia.