Eleftherios Chatzellis

Somatostatin and dopamine receptor expression in neuroendocrine neoplasms: correlation of immunohistochemical findings with somatostatin receptor scintigraphy visual scores

The expression of somatostatin (sstr1‐5) and dopamine (DR) receptors in neuroendocrine neoplasms (NENs) facilitates diagnosis by tumour visualization with somatostatin receptor scintigraphy (SRS) and directs towards specific treatment with peptide receptor radionuclide therapy (PRRT) with radiolabelled somatostatin analogues.

Appendiceal neuroendocrine neoplasms: diagnosis and management

Gastrointestinal neuroendocrine neoplasms (GI-NENs) are increasingly being recognised, while appendiceal NENs (aNENs) currently constitute the third most common GI-NEN. Appendiceal NENs are generally considered to follow an indolent course with the majority being localised at diagnosis. Thus, the initial surgical approach is not that of a planned oncological resection. Due to the localised nature of the disease in the majority of cases, subsequent biochemical and radiological assessment are not routinely recommended. Histopathological criteria (size, mesoappendiceal invasion, Ki-67 proliferation index, neuro- and angio-invasion) are mainly used to identify those patients who are also candidates for a right hemicolectomy. Goblet cell carcinoids are a distinct entity and should be treated as adenocarcinomas. Despite the absence of any substantial prospective data regarding optimal management and follow-up, recent consensus statements and guidelines have been published. The purpose of this review is to overview the published studies on the diagnosis and management of appendiceal NENs and to suggest a possible management protocol.

New Molecular, Biological, and Immunological Agents Inducing Hypophysitis

Hypophysitis is a relatively rare disease that exerts a strong autoimmune component encompassing different etiologies. Immunomodulatory drugs, such as interferon-α, are known to rarely induce hypophysitis. In recent years, a large number of new biological and immunomodulatory agents have been introduced into clinical practice. Although immune-suppressing agents used for the treatment of autoimmune disorders only rarely are associated with hypophysitis, it is commonly encountered with immunomodulatory agents used for the treatment of cancer. Hypophysitis related to anti-cytotoxic T-lymphocyte-associated antigen-4 antibodies (anti-CTLA-4 Abs) occurs with a prevalence ranging from 0 to 18% and is considered a distinctive side effect of anti-CTLA-4 Abs treatment. Hypophysitis due to the programmed cell death protein-1 antibodies and their ligand is less common, its frequency ranging from 0 to 0.8%. No cases of hypophysitis have been described with molecular targeted agents. Diagnosis of hypophysitis still remains clinical since anti-pituitary antibodies are not a sensitive marker and thus its true prevalence is probably underestimated. The pathophysiology of hypophysitis induced by anticancer agents is not fully clarified. In most cases, treatment requires dose adjustment of the offending drug and pituitary hormone replacement. This mini-review aims to present currently available information regarding hypophysitis related to new molecular, biological, and immunological agents.

Pancreatic carcinoids (serotonin-producing pancreatic neuroendocrine neoplasms): Report of 5 cases and review of the literature

Introduction: Pancreatic neuroendocrine neoplasms (pNENs) are relatively rare tumors representing 1% to 2% of all pancreatic neoplasms. These tumors can secrete a variety of biologically active substances giving rise to distinct clinical symptoms or can be clinically nonfunctioning. Apart from insulinomas and gastrinomas, which constitute the majority of functioning pNENs, some tumors may secrete serotonin presenting with the features of the carcinoid syndrome. These so-called pancreatic carcinoids are considered relatively rare tumors and are associated with increased urinary levels of 5-hydroxyindoleacetic acid (5-HIAA). It has recently been suggested that the prevalence of such tumors might be underestimated. Cases: We present a series of 5 patients from our database of 138 pNENs (5/138, 3.62%), harboring serotonin-producing pNENs and describe their distinctive clinical, biochemical, histopathological features, and response to treatment along with a review of the relevant available literature. Conclusion: Such tumors are considered rare, although this may be an underestimate as systematic screening for the presence of serotonin in tissue or elevated urinary 5-HIAA levels in patients with apparently nonfunctioning pNENs is not currently recommended. In order to reach such a consensus, data from large prospective studies are needed in order to evaluate the impact of this type of tumors in survival and clinical outcome, since some studies have suggested a worse prognosis.

Pancreatic Neuroendocrine Tumors Presenting with Hypercalcitonemia

ABSTRACT Objective: Pancreatic neuroendocrine tumors (pNETs) can be associated with discrete clinical syndromes due to the secretion of a variety of bioactive substances that are used to confirm the diagnosis and as potential tumor markers. Calcitonin (Ct) is mainly secreted by medullary thyroid carcinoma (MTC) but is also rarely secreted by pNETs, occasionally leading to diagnostic confusion. We report the diagnosis of 4 patients with metastatic pNETs and associated Ct secretion who were initially evaluated for thyroid pathology. Methods: We describe the histories of 4 patients who were referred for evaluation of thyroid diseases and proved to have metastatic pNETs and associated Ct secretion. One of the patients had erroneously undergone thyroidectomy as hypercalcitonemia was attributed to MTC. Results: Patients presented with variable Ct levels (4-fold up to 35-fold elevations), and all had thyroid nodules that were considered the cause of hypercalcitonemia. Ultrasonography and fine-needle aspiration c...

Somatostatin Receptor Expression in Gastrointestinal Tumors

Somatostatin (SST) receptors belong to the seven-transmembrane domain G-protein-coupled receptors superfamily and exist in five different subtypes. They are widely distributed in many tissues in the human body where they mediate several physiological actions of the native SST hormone. In addition, they are also overexpressed in many tumor cells especially in pituitary adenomas and neuroendocrine neoplasms of the gastrointestinal system. This fact has constituted the basis for development of highly specific and sensitive imaging modalities for in vivo visualization and selective irradiation of such tumors using radiolabeled SST analogues. However, heterogeneous distribution of the five known SST receptor subtypes between different tumor types, and even within the same tumor, can be challenging in the diagnostic approach and can produce considerable variability in responsiveness to therapies targeting these receptors. Therefore, detection of SST receptors and subtype profiling using in vivo and in vitro methods is increasingly gaining clinical attention.