Myeloid and T-Cell Microenvironment Immune Features Identify Two Prognostic Sub-Groups in High-Grade Gastroenteropancreatic Neuroendocrine Neoplasms.

High-grade Gastroenteropancreatic Neuroendocrine neoplasms (H-NENs) comprehend well-differentiated tumors (NET G3) and poorly differentiated carcinomas (NEC) with proliferative activity indexes as mitotic count (MC) >20 mitoses/10 HPF and Ki-67 >20%. At present, no specific therapy for H-NENs exists and the several evidences of microenvironment involvement in their pathogenesis pave the way for tailored therapies. Forty-five consecutive cases, with available information about T-cell, immune, and non-immune markers, from surgical pathology and clinical databases of 2 Italian institutions were immunostained for Arginase, CD33, CD163 and CD66 myeloid markers. The association between features was assessed by Spearman's correlation coefficient. A unsupervised K-means algorithm was used to identify clusters of patients according to inputs of microenvironment features and the relationship between clusters and clinicopathological features, including cancer-specific survival (CSS), was analyzed. The H-NEN population was composed of 6 (13.3%) NET G3 and 39 (86.7%) NEC. Overall, significant positive associations were found between myeloid (CD33, CD163 and Arginase) and T/immune markers (CD3, CD4, CD8, PD-1 and HLA-I). Myeloid and T-cell markers CD3 and CD8 identified two clusters of patients from unsupervised K-means analysis. Cases grouped in cluster 1 with more myeloid infiltrates, T cell, HLA and expression of inhibitory receptors and ligands in the stroma (PD-1, PD-L1) had significantly better CSS than patients in cluster 2. Multivariable analysis showed that Ki-67 (>55 vs. <55, HR 8.60, CI 95% 2.61-28.33, p < 0.0001) and cluster (1 vs. 2, HR 0.43, CI 95% 0.20-0.93, p = 0.03) were significantly associated with survival. High grade gastroenteropancreatic neuroendocrine neoplasms can be further classified into two prognostic sub-populations of tumors driven by different tumor microenvironments and immune features able to generate the framework for evaluating new therapeutic strategies.

Sinonasal cancer encroaching the orbit: Ablation or preservation?

BACKGROUND: Encroachment on the orbital cavity represents a challenge in the management of sinonasal cancer. Criteria guiding orbital preservation lack univocal consensus. Stage of orbital involvement is best assessed through magnetic resonance imaging (MRI). METHODS: Patients affected by orbit-encroaching sinonasal cancer with available preoperative MRI, receiving surgery-based treatment at the University of Brescia between May 2005 and October 2018 were included. All cases were reviewed by expert radiologists and pathologists. Diagnostic performance of MRI was calculated using pathological information as reference. Survival analysis was performed. RESULTS: The study included 123 patients. The orbit was abutted in 53 (43.1%) patients, whereas orbital invasion reached the periorbit in 18 (14.6%), extraconal fat and/or medial lacrimal sac in 29 (23.6%), extrinsic ocular muscles in 7 (5.7%), intraconal compartment in 4 (3.3%), and orbital apex in 12 (9.8%). Seventy-six (61.8%) patients received orbit-sparing surgery, 47 (38.2%) underwent orbital ablation (OA). Accuracy of MRI in detecting involvement by cancer was ≥80.0% for the orbital wall, extraconal fat, and muscles, and <80.0% for the periorbit and intraconal compartment. Previous surgery, neoadjuvant chemotherapy, and perineural invasion decreased MRI accuracy. Age, histology, tumor grade, pT category, N status, perineural invasion, orbital invasion stage, and need for OA were found to affect prognosis. Five-year orbital dysfunction-free survival was 92.8%. CONCLUSION: Conservative management of sinonasal cancers encroaching the orbit is feasible. MRI is essential to preoperatively stage orbital invasion, yet with some limitation. Given the dismal prognosis despite aggressive surgery, neoadjuvant non-surgical therapies should be considered in patients requiring OA.

Colonic hypereosinophilia in ulcerative colitis may help to predict the failure of steroid therapy.

BACKGROUND: Although glucocorticosteroids (GS) and mesalazine are effective and widely employed to treat moderate-to-severe ulcerative colitis (UC), information regarding the factors responsible for response to such therapy is still scarce. One of these factors is thought to be an increased number of mucosal eosinophils. The aim of our study was to determine whether the presence of hypereosinophilia in colonic mucosa of UC patients might influence the short-term response to l treatment with GS and mesasalazine. METHODS: Clinical, endoscopic, and pathologic data from patients with a recent diagnosis of moderate UC, who had not undergone treatment, were obtained, and the short-term outcome after 1 month of conventional first-line treatment (mesalazine plus GS) was evaluated. RESULTS: There were 53 patients with a median age of 37 years (95% CI 30-47).Overall, at the end of treatment period 16 (30%) patients responded, whereas a response was not observed in the other 37 (70%) patients. Interestingly, all patients of this latter group had colonic mucosal hypereosinophilia. No significant differences were found between the two groups concerning sex and age at diagnosis, but hypereosinophilia was inversely correlated with the duration of the disease (p = 0.054), and significantly correlated to the localization of UC (p = 0.0023). In addition, The Mayo score was significantly higher in patients with hypereosinophilia (median 8; 95% CI 8-9;) when compared to patients without hypereosinophilia (median 7; 95% CI 7-7, p < 0.0001) including the Mayo endoscopic subscore (median 3; 95% CI 2-3 vs median 2; 95% CI 2-2, respectively; p = 0.007). CONCLUSIONS: The presence of colonic mucosal hypereosinophilia may be useful to predict the short-term outcome to conventional first-line therapy in treatment-naïve UC patients. It remains to be seen whether this might be important in modifying the first-line therapy in this subgroup of patients.

Celiac disease and obstetrical-gynecological contribution.

Celiac disease (CD) shows an increased prevalence in female, particularly during the fertile period. Celiac disease should be researched in infertility, spontaneous and recurrent abortions, delayed menarche, amenorrhea, early menopause, and children with low birth-weight. Celiac disease is still little considered during the evaluation of infertility. Up to 50% of women with untreated CD refer an experience of miscarriage or an unfavorable outcome of pregnancy. Celiac patients taking a normal diet (with gluten) have a shorter reproductive period. Women with undiagnosed CD had a higher risk of small for gestation age infants very small for gestational age infants and pre-term birth when compared with women with noted CD. The link between NCGS and infertility is actually unknown. The goal of our work is to perform an actual review about this topic and to increase the awareness in the medical population to research celiac disease in selected obstetric and gynecological disorders.