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Massironi S.,Gastroenterology Unit II | Conte D.,Gastroenterology Unit II | Conte D.,University of Milan | Sciola V.,Gastroenterology Unit II | And 8 more authors.
American Journal of Gastroenterology | Year: 2010

Objectives: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) expressing somatostatin receptors may be treated with somatostatin analogs (SSAs). Selection criteria are a positive Octreoscan or a 50% hormone level decrease after octreotide subcutaneous (s.c.) injection (octreotide test) (OT). Plasma chromogranin A (CgA) is the best general GEP-NET marker, but data on CgA response to OT are scanty. Thus, we evaluated whether plasma CgA response to OT could predict the clinical response to SSAs. Methods: At diagnosis, 38 GEP-NET patients received octreotide 200 g s.c., with plasma CgA determination at 0, 3, and 6 h. Long-term SSA treatment was then given by monitoring symptomatic, biochemical, and objective responses, and survival. Results: Basal plasma CgA levels were significantly higher in patients with functioning than non-functioning tumors (median (range): 220 (18-2,230) vs. 46 (25-8,610) U/l, P>0.03) and in those with than without metastases (171 (18-8,610) vs. 43 (28-220) U/l, P>0.04). CgA levels significantly correlated with WHO classification, clinical TNM staging, and Ki-67 proliferative index. After OT, CgA levels decreased from 146 (18-8,610) to 61 (10-8,535) U/l (basal and nadir values), P>0.001. In patients responsive to OT, a successful objective response occurred in 21/31 patients (68%). Successful symptomatic response occurred in 13/18 patients (72%), biochemical response in 25/31 (81%), and objective response in 21/31 (68%). In the remaining seven unresponsive cases, with CgA decrement 30%, disease progressed to death in six (86%). Median survival from enrollment was 48 months (6-138) in responsive and 6 (6-30) in unresponsive patients (P>0.0005). Conclusions: In GEP-NETs, plasma CgA is a reliable marker, and a 30% decrease after OT has a relevant prognostic meaning allowing the identification of the subgroup of patients most likely to be responsive to chronic SSAs. © 2010 by the American College of Gastroenterology.


Orlando A.,Cervello | Mocciaro F.,ARNAS Civico Hospital | Renna S.,Cervello | Scimeca D.,Casa Sollievo della Sofferenza Hospital | And 21 more authors.
Journal of Crohn's and Colitis | Year: 2014

Introduction: The incidence of endoscopic recurrence (ER) in Crohn's disease following curative resection is up to 75% at 1. year. Endoscopy is the most sensitive method to detect the earliest mucosal changes and the severe ER at 1. year seems to predict a clinical relapse. Methods: The aim of this prospective study was to evaluate the incidence of early ER 6. months after curative resection. Secondary outcome was to evaluate the role of 5-aminosalicylic acid (5-ASA) in the prevention of ER at 6. months. A total of 170 patients were included in the study. They were carried-out from the evaluation of the appearance of ER during a trial performed to assess the role of azathioprine vs. 5-ASA as early treatment of severe ER. All the patients started 5-ASA treatment 2. weeks after surgery. Results: Six months after surgery ER was observed in 105 patients (62%). The endoscopic score was reported as severe in 78.1% of them (82 out of 105). At univariable analysis only ileo-colonic disease influenced the final outcome associating to a lower risk of severe ER (p. =. 0.04; OR 0.52, 95% CI 0.277-0.974). Conclusion: In this prospective Italian multicenter IG-IBD study a great proportion of ER occur within 6. months from ileo-colonic resection, with a significant rate of severe ER. Furthermore this study confirms the marginal role of 5-ASA in the prevention of ER. This suggests that post-surgical endoscopic evaluation should be performed at 6. months instead of 1. year to allow an adequate early treatment. © 2014 European Crohn's and Colitis Organisation.


Fiori S.,Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico | Del Gobbo A.,Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico | Gaudioso G.,Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico | Caccamo L.,Liver Transplant Unit | And 6 more authors.
Diagnostic Pathology | Year: 2013

Imaging appearance of cyst-like changes is most frequently described in primary neuroendocrine lesions, especially pancreatic NETs.The imaging finding of a pseudocystic lesion of the liver puts in differential diagnosis many pathologies such as infectious diseases, simple biliary cysts up to biliary cystadenomas and eventually to primary or metastatic malignancies.Primary or metastatic hepatic malignancies with pseudocystic aspects are rare, and a pseudocystic aspect is reported only after neo-adjuvant treatment.Liver metastasis of untreated neuroendocrine tumors are usually solid and, to our knowledge, only two cases of neuroendocrine cystic hepatic metastases of ileal atypical carcinoids have been reported so far.We present a case of a 67 years old man with synchronous finding of an untreated hepatic pseudocystic lesion and an ileal mass histologically diagnosed as a well differentiated (G1) neuroendocrine tumor. The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1443883503102967. © 2013 Fiori et al.; licensee BioMed Central Ltd.


Rossi R.E.,University of Milan | Rossi R.E.,Gastroenterology Unit II | Massironi S.,Gastroenterology Unit II | Spampatti M.P.,University of Milan | And 6 more authors.
Journal of Gastrointestinal Surgery | Year: 2012

Background: Liver metastases are a strong prognostic indicator in patients with gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs). Therapeutic options for metastatic NETs are expanding and not mutually exclusive. Aims: This paper reviews the literature relating to multidisciplinary approach towards GEP-NET metastases, to highlight advances in knowledge regarding these tumors, and to understand the interdisciplinary management of individual patients. Methods: A PubMed search was performed for English-language publications from 1995 through 2012. Reference lists from studies selected were manually searched to identify further relevant reports. Manuscripts comparing different therapeutic options and advances for GEP-NET-related liver metastases were selected. Results: There is considerable controversy regarding the optimal management of GEP-NET metastases. Although radical surgery still remains the gold standard, a variety of other therapeutic options are available for metastatic GEP-NETs, including loco-regional chemotherapy/radiotherapy, radioembolization, systemic peptide receptor radionuclide therapy, biotherapy, and chemotherapy. In selected patients, liver transplantation should also be considered. Systemic somatostatin analogues and/or interferon show anti-proliferative effects, representing an appropriate first-line treatment for most patients. In advanced metastatic NETs, recent options include targeted therapies (i.e., everolimus and sunitinib). Conclusions: It is evident that multidisciplinary care and multimodality treatments remain the cornerstone of management of NET patients. Since NETs often show a more indolent behavior compared to other malignancies, physicians should aim to preserve a satisfactory quality of life for the patient by personalizing the therapeutic approach according to the tumor's features and prognostic factors. © 2012 The Society for Surgery of the Alimentary Tract.


Massironi S.,Gastroenterology Unit II | Conte D.,Gastroenterology Unit II | Conte D.,University of Milan | Sciola V.,Gastroenterology Unit II | And 9 more authors.
Digestive and Liver Disease | Year: 2010

Objectives: At presentation, gastroenteropancreatic neuroendocrine tumours (GEP NETs) frequently show prognostically negative hepatic involvement. The aim of this study was to characterise hepatic metastases of GEP NETs as revealed by contrast-enhanced ultrasonography (CEUS), which allows the fine definition of the microvascular system, and to correlate these findings to the biological behaviour of the tumour. Methods: Eighteen out of 62 GEP NET patients examined between January 2007 and September 2008 had histologically proven hepatic metastases from primary ileal (#6), gastric (#1) or rectal (#1) carcinoids, pancreatic tumours (#7), or primary duodenal (#2) or occult gastrinomas (#1), and all underwent low mechanical index real-time CEUS with SonoVue ® injection. Results: Strong early enhancement in the arterial phase was observed in 15 cases (83%), and a rapid wash-out in the portal venous phase in 14 (78%). In the late venous phase, the lesions were hypoechoic in 12 cases (67%), isoechoic in five (28%), and hyperechoic in one (0.05%). The time of arterial enhancement correlated with the Ki-67 proliferative index (r s=0.516; p=0.028). Conclusions: Most of the neuroendocrine liver metastases showed increased arterial enhancement at CEUS, a behaviour that is similar to that of hepatocellular carcinomas and the opposite of that of other metastases. CEUS can be a useful diagnostic means of characterising such metastases. © 2010.


Massironi S.,Gastroenterology Unit II | Rossi R.E.,Gastroenterology Unit II | Rossi R.E.,University of Milan | Cavalcoli F.A.,Gastroenterology Unit II | And 6 more authors.
Clinical Nutrition | Year: 2013

Background & aims: Malnutrition is common in inflammatory bowel diseases (IBD), mainly in Crohn's disease (CD) because the small bowel is primarily affected. We reviewed the literature to highlight the importance of proper nutrition management. Methods: A PubMed search was performed for English-language publications from 1999 through 2012. Manuscripts comparing nutritional approaches for IBD patients were selected. Results: We identified 2025 manuscripts: six meta-analyses, 170 clinical-trials, 692 reviews. The study findings are discordant. In adult CD, enteral nutrition plays a supportive role, steroid therapy remaining the first choice treatment. In CD children enteral nutrition may represent the primary therapy. As regards parenteral nutrition, there are no large randomized studies, although mild improvements in morbidity have been described as a result of parenteral nutrition in malnourished surgical IBD patients. Specific micronutrient deficiencies are common in IBD. A number of factors may contribute to micronutrient deficiencies, and these include: dietary restriction, disease activity and surgery.The possible therapeutic roles of omega-3 fatty-acids, probiotics and prebiotics have been studied, but the results are still preliminary. Conclusion: Protein-energy malnutrition and micronutrient depletion are clinical concerns in IBD patients. Enteral nutrition, parenteral nutrition and micronutrient supplementation are cornerstone of the multidisciplinary management of IBD patients. © 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism.


PubMed | Gastroenterology Unit II
Type: Journal Article | Journal: The American journal of gastroenterology | Year: 2010

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) expressing somatostatin receptors may be treated with somatostatin analogs (SSAs). Selection criteria are a positive Octreoscan or a >50% hormone level decrease after octreotide subcutaneous (s.c.) injection (octreotide test) (OT). Plasma chromogranin A (CgA) is the best general GEP-NET marker, but data on CgA response to OT are scanty. Thus, we evaluated whether plasma CgA response to OT could predict the clinical response to SSAs.At diagnosis, 38 GEP-NET patients received octreotide 200 microg s.c., with plasma CgA determination at 0, 3, and 6 h. Long-term SSA treatment was then given by monitoring symptomatic, biochemical, and objective responses, and survival.Basal plasma CgA levels were significantly higher in patients with functioning than non-functioning tumors (median (range): 220 (18-2,230) vs. 46 (25-8,610) U/l, P=0.03) and in those with than without metastases (171 (18-8,610) vs. 43 (28-220) U/l, P=0.04). CgA levels significantly correlated with WHO classification, clinical TNM staging, and Ki-67 proliferative index. After OT, CgA levels decreased from 146 (18-8,610) to 61 (10-8,535) U/l (basal and nadir values), P<0.001. In patients responsive to OT, a successful objective response occurred in 21/31 patients (68%). Successful symptomatic response occurred in 13/18 patients (72%), biochemical response in 25/31 (81%), and objective response in 21/31 (68%). In the remaining seven unresponsive cases, with CgA decrement <30%, disease progressed to death in six (86%). Median survival from enrollment was 48 months (6-138) in responsive and 6 (6-30) in unresponsive patients (P=0.0005).In GEP-NETs, plasma CgA is a reliable marker, and a >30% decrease after OT has a relevant prognostic meaning allowing the identification of the subgroup of patients most likely to be responsive to chronic SSAs.


PubMed | Gastroenterology Unit II
Type: Journal Article | Journal: Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver | Year: 2010

At presentation, gastroenteropancreatic neuroendocrine tumours (GEP NETs) frequently show prognostically negative hepatic involvement. The aim of this study was to characterise hepatic metastases of GEP NETs as revealed by contrast-enhanced ultrasonography (CEUS), which allows the fine definition of the microvascular system, and to correlate these findings to the biological behaviour of the tumour.Eighteen out of 62 GEP NET patients examined between January 2007 and September 2008 had histologically proven hepatic metastases from primary ileal (#6), gastric (#1) or rectal (#1) carcinoids, pancreatic tumours (#7), or primary duodenal (#2) or occult gastrinomas (#1), and all underwent low mechanical index real-time CEUS with SonoVue injection.Strong early enhancement in the arterial phase was observed in 15 cases (83%), and a rapid wash-out in the portal venous phase in 14 (78%). In the late venous phase, the lesions were hypoechoic in 12 cases (67%), isoechoic in five (28%), and hyperechoic in one (0.05%). The time of arterial enhancement correlated with the Ki-67 proliferative index (r(s)=0.516; p=0.028).Most of the neuroendocrine liver metastases showed increased arterial enhancement at CEUS, a behaviour that is similar to that of hepatocellular carcinomas and the opposite of that of other metastases. CEUS can be a useful diagnostic means of characterising such metastases.


PubMed | Gastroenterology Unit II
Type: Journal Article | Journal: European journal of endocrinology | Year: 2013

The coexistence of chronic autoimmune atrophic gastritis (CAAG) and primary hyperparathyroidism (PHPT) has been described previously, even if its extent and underlying mechanisms remain poorly understood. We therefore prospectively evaluated this association in two series of patients, one with CAAG and the other with sporadic PHPT.From January 2005 to March 2012, 107 histologically confirmed CAAG patients and 149 PHPT patients were consecutively enrolled. Routine laboratory assays included serum calcium, parathyroid hormone (PTH), plasma gastrin and chromogranin A (CgA). In CAAG patients with high PTH levels, ionized calcium and 25(OH)-vitamin D were evaluated. All CAAG and hypergastrinemic PHPT patients received an upper gastrointestinal endoscopy. Exclusion criteria were familial PHPT, MEN1 syndrome, treatment with proton pump inhibitor drugs, Helicobacter pylori infection and renal failure.Of the 107 CAAG patients, nine (8.4%) had PHPT and 13 (12.1%) had secondary hyperparathyroidism stemming from vitamin D deficiency. Among the 149 PHPT patients, 11 (7.4%) had CAAG. Gastrin and CgA levels were similar in the CAAG patients with vs those without hyperparathyroidism (either primary or secondary), and calcium and PTH levels were similar in the PHPT patients with vs those without CAAG.This study confirms a non-casual association between PHPT and CAAG. The prevalence of PHPT in CAAG patients is threefold that of the general population (8.4 vs 1-3%), and the prevalence of CAAG in PHPT patients is fourfold that of the general population (7.4 vs 2%). The mechanisms underlying this association remain unknown, but a potential role for autoimmunity is suggested.


PubMed | Gastroenterology Unit II
Type: Journal Article | Journal: Clinical nutrition (Edinburgh, Scotland) | Year: 2013

Malnutrition is common in inflammatory bowel diseases (IBD), mainly in Crohns disease (CD) because the small bowel is primarily affected. We reviewed the literature to highlight the importance of proper nutrition management.A PubMed search was performed for English-language publications from 1999 through 2012. Manuscripts comparing nutritional approaches for IBD patients were selected.We identified 2025 manuscripts: six meta-analyses, 170 clinical-trials, 692 reviews. The study findings are discordant. In adult CD, enteral nutrition plays a supportive role, steroid therapy remaining the first choice treatment. In CD children enteral nutrition may represent the primary therapy. As regards parenteral nutrition, there are no large randomized studies, although mild improvements in morbidity have been described as a result of parenteral nutrition in malnourished surgical IBD patients. Specific micronutrient deficiencies are common in IBD. A number of factors may contribute to micronutrient deficiencies, and these include: dietary restriction, disease activity and surgery. The possible therapeutic roles of omega-3 fatty-acids, probiotics and prebiotics have been studied, but the results are still preliminary.Protein-energy malnutrition and micronutrient depletion are clinical concerns in IBD patients. Enteral nutrition, parenteral nutrition and micronutrient supplementation are cornerstone of the multidisciplinary management of IBD patients.

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