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      Peritoneal Carcinomatosis in Gastro-Entero-Pancreatic Neuroendocrine Neoplasms: Clinical Impact and Effectiveness of the Available Therapeutic Options

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          Background: Peritoneal carcinomatosis (PC) can affect the quality of life of patients with gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs). Peritoneal disease control by medical therapies in these patients has been poorly investigated Objectives: To describe, in a consecutive series of GEP-NENs, the clinical impact of PC and to report the effectiveness of available treatments in PC control. Methods: A retrospective, monocenter analysis was performed of 135 GEP-NENs (1993–2016) with at least a 12-month follow-up. Peritoneal disease progression was defined as detection of a significant increase in size or appearance of new implants by imaging. Results: A total of 62.9% of cases had diffuse PC (involving at least 2 abdominal quadrants). According to WHO 2017 classification, cases were 42.3% neuroendocrine tumors NET-G1, 45.5% NET-G2, 6.5% NET-G3, 4.9% neuroendocrine carcinomas NEC-G3, and 0.8% mixed neuroendocrine-nonneuroendocrine neoplasms. Bowel obstruction occurred in 30 (22.2%) patients mainly depending on size of peritoneal implants (HR: 1.10; 95% CI: 1.02–1.20; p = 0.01). Patients with diffuse PC treated with peptide receptor radionuclide therapy (PRRT) showed peritoneal progression in 37.5% of cases, and bowel obstruction or ascites in 28.1%. Better peritoneal disease control was observed in cases receiving somatostatin analogs at first-line therapy, probably due to a less aggressive disease behavior for these patients. Conclusions: Bowel obstruction is not uncommon in GEP-NENs with PC. PRRT should be adopted with caution in GEP-NENs with diffuse PC, but larger series are needed to confirm these data.

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          Most cited references 18

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          TNM staging of midgut and hindgut (neuro) endocrine tumors: a consensus proposal including a grading system.

          Criteria for the staging and grading of neuroendocrine tumors (NETs) of midgut and hindgut origin were established at the second Consensus Conference in Frascati (Rome) organized by the European Neuroendocrine Tumor Society (ENETS). The proposed tumor-node-metastasis (TNM) classifications are based on the recently published ENETS Guidelines for the Diagnosis and Treatment of gastroenteropancreatic NETs and follow our previous proposal for foregut tumors. The new TNM classifications for NETs of the ileum, appendix, colon, and rectum, and the grading system were designed, discussed, and consensually approved by all conference participants. These proposals need to be validated and are meant to help clinicians in the stratification, treatment and follow-up of patients.
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            ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: Radiological, Nuclear Medicine and Hybrid Imaging

             Anders Sundin (corresponding) ,  Rudolf Arnold,  Eric Baudin (2017)
            Contrast-enhanced computed tomography (CT) of the neck-thorax-abdomen and pelvis, including 3-phase examination of the liver, constitutes the basic imaging for primary neuroendocrine tumor (NET) diagnosis, staging, surveillance, and therapy monitoring. CT characterization of lymph nodes is difficult because of inadequate size criteria (short axis diameter), and bone metastases are often missed. Contrast-enhanced magnetic resonance imaging (MRI) including diffusion-weighted imaging is preferred for the examination of the liver, pancreas, brain and bone. MRI may miss small lung metastases. MRI is less well suited than CT for the examination of extended body areas because of the longer examination procedure. Ultrasonography (US) frequently provides the initial diagnosis of liver metastases and contrast-enhanced US is excellent to characterize liver lesions that remain equivocal on CT/MRI. US is the method of choice to guide the biopsy needle for the histopathological NET diagnosis. US cannot visualize thoracic NET lesions for which CT-guided biopsy therefore is used. Endocopic US is the most sensitive method to diagnose pancreatic NETs, and additionally allows for biopsy. Intraoperative US facilitates lesion detection in the pancreas and liver. Somatostatin receptor imaging should be a part of the tumor staging, preoperative imaging and restaging, for which 68 Ga-DOTA-somatostatin analog PET/CT is recommended, which is vastly superior to somatostatin receptor scintigraphy, and facilitates the diagnosis of most types of NET lesions, for example lymph node metastases, bone metastases, liver metastases, peritoneal lesions, and primary small intestinal NETs. 18 FDG-PET/CT is better suited for G3 and high G2 NETs, which generally have higher glucose metabolism and less somatostatin receptor expression than low-grade NETs, and additionally provides prognostic information.
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              ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Neoplasms: Peptide Receptor Radionuclide Therapy with Radiolabelled Somatostatin Analogues

               Rodney Hicks (corresponding) ,  Dik Kwekkeboom,  Eric Krenning (2017)
              The purpose of these guidelines is to assist physicians caring for patients with neuroendocrine neoplasia in considering eligibility criteria for peptide receptor radionuclide therapy (PRRT) and in defining the minimum requirements for PRRT. It is not these guidelines' aim to give recommendations on the use of specific radiolabelled somatostatin analogues for PRRT as different analogues are being used, and their availability is governed by varying international regulations. However, a recent randomized controlled trial, NETTER-1, has provided evidence that may establish 177 Lu-DOTA-octreotate (LutaThera®) as the first widely approved agent. It also makes recommendations on what minimal patient, tumour, and treatment outcome characteristics should be reported for PRRT to facilitate robust comparisons between studies.

                Author and article information

                S. Karger AG
                May 2020
                05 September 2019
                : 110
                : 6
                : 517-524
                aDepartment of Gastroenterology, Azienda Provinciale per i Servizi Sanitari (APSS), Trento, Italy
                bDepartment of Medicine, Division of Endocrinology, Friedrich Alexander University Erlangen-Nürnberg, Erlangen, Germany
                cDepartment of Nuclear Medicine, University Hospital of Ulm, Ulm, Germany
                dDepartment of Nuclear Medicine, Charité Universitätsmedizin, Berlin, Germany
                eKlinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Münster, Münster, Germany
                fDepartment of General, Visceral and Transplantation Surgery, Charité Universitätsmedizin, Berlin, Germany
                gDepartment of Hepatology and Gastroenterology, Charité Universitätsmedizin, Berlin, Germany
                hInstitute of Pathology, Charité University Hospital, Berlin, Germany
                iDepartment of Diagnostic and Interventional Radiology, University of Leipzig Medical Center, Leipzig, Germany
                jDepartment of Diagnostic and Interventional Radiology, Charité Universitätsmedizin, Berlin, Germany
                Author notes
                *Dr. Elettra Merola, Department of Gastroenterology, Azienda Provinciale Servizi Sanitari (APSS), Largo Medaglie D’Oro 9, IT–3122 Trento (Italy), E-Mail elettra.merola@gmail.com
                503144 Neuroendocrinology 2020;110:517–524
                © 2019 S. Karger AG, Basel

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                Page count
                Figures: 3, Tables: 5, Pages: 8
                Research Article


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