BACKGROUND: Gastroenteric neuroendocrine neoplasms (GE‐NENs) display highly variable clinical behavior. In an attempt to assess a better prognostic description, in 2010, the World Health Organization (WHO) updated its previous classification, and the European Neuroendocrine Tumors Society (ENETS) proposed a new grading and TNM‐based staging system. In the current study, the authors evaluated the prognostic significance of these models and compared their efficacy in describing patients' long‐term survival to assess the best prognostic model currently available for clinicians.METHODS: The study cohort was composed of 145 patients with extrapancreatic GE‐NEN who were observed from 1986 to 2008 at a single center and were classified according to the WHO and ENETS classifications. Survival evaluations were performed using Kaplan‐Meyer analyses on 131 patients. Only deaths from neoplasia were considered. A P value < .05 was considered significant. Prognostic efficacy was assessed by determining the Harrell concordance index (c‐index).RESULTS: Both the 2010 WHO and the ENETS classification were able to efficiently divide patients into classes with different prognoses. According to the model comparison, the ENETS TNM‐based staging system appeared to be the strongest. All combined models were effective prognostic predictors, but the model that included the 2010 WHO classification plus ENETS staging had a higher c‐index.CONCLUSIONS: Both the 2010 WHO classification and the ENETS staging system are valid instruments for GE‐NENs prognostic assessment, with TNM‐based stage appearing to be the best available choice for clinicians, both alone and in association with other classifications. Cancer 2013. © 2012 American Cancer Society.

Chromogranin A (CgA) is a plasma biomarker widely used in the follow-up of patients with neuroendocrine neoplasms (NENs). However, its accuracy as a tumor biomarker is relatively low because plasma CgA can increase also in patients with other diseases or in subjects treated with proton-pump inhibitors (PPIs), a class of widely-used drugs. In the attempt to identify a more reliable biomarker for NENs, we investigated, by ELISA, the circulating levels of full-length CgA (CgA_1-439) and of various CgA-derived fragments in 17 patients with ileal or pancreatic NENs, 10 healthy controls, and 21 healthy volunteers before and after treatment with PPIs. Patients with ileal or pancreatic NENs showed increased plasma levels of total-CgA and CgA_1-76 fragment (vasostatin-1, VS-1) compared to controls [median (25^th-75^th-percentiles); total-CgA: 1.85 nM (1.01–4.28) vs 0.75 nM (0.52–0.89), p = 0.004; VS-1: 2.76 nM (1.09–7.10) vs 0.29 nM (0.26–0.32), p<0.001, respectively], but not of CgA_1-439 or CgA_1-373 fragment. VS-1 positively correlated with total-CgA (r = 0.65, p<0.001). The Receiver Operating Characteristic area under the curve was 0.9935 for VS-1 and 0.8824 for total-CgA (p = 0.067). Treatment of patients with somatostatin analogues decreased both total-CgA and VS-1. In contrast, administration of PPIs increased the plasma levels of total-CgA, but not of VS-1. These findings suggest that plasma VS-1 is a novel biomarker for ileal and pancreatic NENs. Considering that VS-1 is a well-defined fragment not induced by proton-pump inhibitors, this polypeptide might represent a biomarker for NENs diagnosis and follow-up more accurate and easier to standardize than CgA.

Papillary thyroid micro-carcinomas are considered relatively indolent carcinomas, often occult and incidental, with good prognosis and favorable outcomes. Despite these findings, central lymph node metastases are common, and are related to a poor prognosis for the patient. We performed a retrospective analysis on patients treated with surgery for stage pT1a papillary thyroid micro-carcinomas. One hundred ninety-five patients were included in the analyses. The presence of central lymph node metastases was identified and studied. A multivariate analysis employing binary logistic regression was used to calculate adjusted odds ratios with 95% confidence intervals of possible central lymph node metastases risk factors. In the performed multivariate analysis, male gender, younger age, and histopathological characteristics, such as a tumor sub-capsular localization, were significantly associated with central lymph node metastases in pT1a patients. Central compartment lymph node metastases are present in a non-negligible number of cases in patients with papillary thyroid micro-carcinoma undergoing surgical resection. Studying these factors could be an effective tool for predicting patients’ central lymph node metastases in papillary thyroid micro-carcinomas, defining a tailored surgical treatment in the future.

Introduction: Surgery is still the main line of treatment for papillary thyroid cancer (PTC) with a current trend for de-intensified treatment based on an excellent prognosis. The role of a routine prophylactic central neck dissection (PCND) is still debated as its impact on oncologic outcomes has never been cleared by a randomized clinical trial. In this study, we aimed to report our long-standing experience in PCND and its potential contemporary role in the treatment of PTC. Methods: A retrospective institutional review was performed on all patients who underwent operation for PTC including PCND between 1998 and 2021. The primary outcomes were the rate of central lymph node metastases (CLNMs), cancer recurrence and incidence of complications. Survivals were analyzed using the Kaplan–Meier estimator and Cox proportional hazard models. Results: A total of 657 patients were included in this study with a median follow-up of 78 months (48–114 months). Two hundred and one patients presented occult CLNMs (30.6%). The presence of a pathological node represented the unique reason for a completion thyroidectomy and I¹³¹ therapy in 12.5% of the population. Age lower than 55 years, microscopic or macroscopic extra-thyroid extension (ETE) and multifocality were independent factors predicting CLNMs. The rate of recurrence in the whole population was 2.7% (18 patients). Five-year and ten-year disease-free survival (DFS) was 96.5% (94.7–97.7) and 93.3% (90.3–95.5), respectively. Two patients relapsed in the central neck compartment (0.3%). Age (>55 years), pathological staging (pT) and extranodal extension (ENE) were independent factors associated with a worse DFS. The rate of temporary and permanent vocal fold palsy was 12.8% and 1.8%, respectively, and did not depend on the type of surgical procedure performed. Hypoparathyroidism was temporary in 42.2% and permanent in 11.9% of the patients. A sub-analysis upon cT1b-T2 patients treated primarily with thyroid lobectomy and ipsilateral PCND demonstrated a 2.6% rate of permanent hypoparathyroidism. Conclusions: PCND allows for a high disease-free survival and a proper selection of patients needing adjuvant treatment, in particular, those treated with a unilateral procedure. On the other hand, bilateral approach is burdened by a not-neglectable rate of permanent hypoparathyroidism.

Objective.Analyzing and managing pre-eclampsia-like syndrome due to severe hypothyroidism.Methods.Presentation of a case of severe hypothyroidism due to Hashimoto’s syndrome, associated with a severe early-onset preeclampsia-like syndrome, managed in our Gynecology Department.Results.Severe pre-eclampsia led to miscarriage at 24 weeks of gestational age in a 42-year-old woman, although we attempted to correct hypothyroidism with increasing doses of levothyroxine and liothyronine sodium.Conclusion.Recognizing pre-eclampsia-like syndrome caused by overt hypothyroidism from other forms of pregnancy-induced hypertension is essential for choosing the correct treatment.

Cytological Ki-67 in pancreatic endocrine tumors: a new “must”?