S. Angeletti

High prevalence of atrophic body gastritis in patients with unexplained microcytic and macrocytic anemia: A prospective screening study

OBJECTIVE: Atrophic body gastritis (ABG) is characterized by atrophy of the gastric body mucosa, hypergastrinemia, and hypo/achlorhydria. Its association with pernicious anemia is well recognized. Gastric hypo/achlorhydria is known to affect iron absorption but ABG is rarely considered as a possible cause of iron deficiency (microcytic) anemia. The aims of this study were to validate a screening methodology for the detection of ABG in a consecutive series of patients with microcytic and macrocytic anemia and to investigate the clinical and gastric morphofunctional characteristics of the two hematological presentations of ABG. METHODS: A two-part prospective study was carried out. Part A aimed to validate the screening methodology to detect the presence of ABG in patients with macrocytic and microcytic anemia who have no specific GI symptoms, by measuring their gastrin levels and verified by performing gastroscopy with biopsy. Part B aimed to detect the presence of ABG in a larger sample of anemic patients by our validated method and, by pooling the data of ABG patients, to determine the clinical, gastric histological, and functional characteristics pertaining to the macrocytic and microcytic presentations of ABG. RESULTS: In part A, ABG was detected in 37.5% of patients with macrocytic and in 19.5% of those with microcytic anemia. Pooling the data of the ABG patients from part A and part B, microcytic ABG patients were on average 20 yr younger than those with macrocytic anemia. The majority of microcytic ABG patients were female, most of whom were premenopausal. H. pylori infection was widely represented in the microcytic ABG group (61.1%). They also had a lesser grade of body mucosal atrophy and lower hypergastrinemia levels, suggesting a less severe oxyntic damage of shorter duration. CONCLUSIONS: Macrocytic anemia is not the only hematological presentation of ABG. Physicians evaluating patients with unexplained iron deficiency anemia should consider ABG as a possible cause by determining fasting gastrin levels and performing gastroscopy with biopsies of the body mucosa.

Reversal of Long-Standing Iron Deficiency Anaemia after Eradication of Helicobacter pylori Infection

Helicobacter pylori has been proposed as a major determinant in multiple gastric disorders. We describe the case of a young adult with a long-standing medical history of sideropenic anaemia and of oral iron consumption dependence with a chronic superficial H. pylori-positive gastritis. All other causes of sideropenic anaemia were carefully excluded. Histology showed a peculiar pattern of non-active H. pylori-positive gastritis. The bacterium was a non-VacA-producing strain. The first attempt at eradication caused a reduction in bacterial load and led to a partial normalization of haematologic variables without improving the ferritin level. A successful second course of eradication therapy completely reversed the anaemia and restored the iron deposit, which persisted at the 29-month follow-up. H. pylori infection can be involved in unexplained cases of iron deficiency anaemia in adults, and its cure can normalize the haematologic picture.

Utility of combined use of plasma levels of chromogranin A and pancreatic polypeptide in the diagnosis of gastrointestinal and pancreatic endocrine tumors.

Background: Chromogranin A (CgA) is considered the most accurate marker in the diagnosis of gastro-entero-pancreatic (GEP) endocrine tumors. Pancreatic polypeptide (PP) has also been proposed to play this role, but then not used due to its low sensitivity. The aim of the present study was to determine whether the assessment of PP would improve the diagnostic reliability of CgA in patients with GEP tumors. Patients and methods: Both markers were assessed in 68 patients [28 functioning (F), 40 non functioning (NF)]. Twenty-seven patients disease-free (DF) after surgery, and 24 with non-endocrine tumors (non-ETs) were used as control groups. Results: CgA sensitivity was: 96% in F, 75% in NF, 74% in pancreatic, and 91% in gastrointestinal (GI) tumors. Specificity was 89% vs DF, and 63% vs non- ETs. PP sensitivity was: 54% in F, 57% in NF, 63% in pancreatic, and 53% in GI tumors. Specificity was 81% vs DF, and 67% vs non-ETs. By combining the two markers a significant gain in sensitivity vs CgA alone was obtained: overall in GEP tumors (96% vs 84%, p=0.04), in NF (95% vs 75%, p=0.02), and in pancreatic (94% vs 74%, p=0.04). More specifically, a 25% gain of sensitivity was obtained in the subgroup of NF pancreatic tumors (93% vs 68%, p=0.04). Conclusion: The combined assessment of PP and CgA leads to a significant increase in sensitivity in the diagnosis of GEP tumors, particularly in pancreatic NF.

Use of the somatostatin analogue octreotide to localise and manage somatostatin-producing tumours

Background—Somatostatin receptor scintigraphy (SRS) and octreotide therapy have both changed the management of gastroenteropancreatic endocrine tumours, but very few data are available on the use of SRS and octreotide to visualise and treat somatostatinomas. Method—The results of SRS and octreotide treatment in three somatostatinoma patients were examined. Results—SRS was able to detect extensive hepatic involvement in patient 1, one hepatic and one pancreatic lesion in patient 2, and one hepatic lesion in patient 3. Octreotide therapy (0.5 mg/day subcutaneously) was effective in decreasing plasma levels of somatostatin in all three patients. Symptoms (diabetes and diarrhoea) were greatly improved in the two patients with “somatostatinoma syndrome”. Conclusion—The study shows that somatostatinoma, like most other gastroenteropancreatic endocrine tumours, possesses functioning somatostatin receptors.

Does the widespread use of proton pump inhibitors mask, complicate and/or delay the diagnosis of Zollinger-Ellison syndrome?

Proton pump inhibitors are potent acid suppressants which, at normal doses, can result in hypergastrinaemia in patients with idiopathic oesophageal reflux disease and in the control of symptoms in most patients with gastrinomas. Therefore, their use could delay or mask the diagnosis of gastrinoma.

Digestive neuroendocrine tumours: diagnosis and treatment in Italy. A survey by the Oncology study Section of the Italian Society of Gastroenterology (SIGE)

BACKGROUND New insights in the diagnosis and treatment of digestive neuroendocrine tumours have prompted a renewed interest in these rare and complex diseases. AIM To establish how many new cases of digestive neuroendocrine tumours were diagnosed, and how they were treated, at gastroenterological centres across Italy during a two-year period (1997-1998). METHODS The 12 centres taking part filled in a data collection form reporting type of tumour, methods of diagnosis and therapeutic strategies adopted in each case. Data were collected and analysed by the authors of the present report. RESULTS Data refer to 98 patients, 22 with functioning and 76 with non-functioning digestive neuroendocrine tumours [50 carcinoids, 48 pancreatic endocrine tumour syndromes]. Primary tumours were localised in 96% (38% with metastases) of non-functioning and 81% (50% with metastases) of functioning tumours. These were surgically removed in >80% of patients in both groups. Somatostatin analogue treatment, with or without interferon, was administered in 35% of patients, while chemotherapy was used in 9% and 23% of functioning and non-functioning tumours, respectively. The imaging study always included a computed tomography scan (20% helical computed tomography). Magnetic resonance and somatostatin receptor scintigraphy were also performed, the former in 41% and 21% of the two (functioning and non-functioning tumour) groups, the latter in 45% and 30%. CONCLUSIONS The number of functioning digestive neuroendocrine tumours reported was lower than expected. Surgery plays a major role in the treatment of these tumours in all centres. Overall, in only a small number of patients was a multidisciplinary approach applied.

HCV-positive status and hepatitis flares in patients with B-cell non-Hodgkin's lymphoma treated with rituximab-containing regimens.

BACKGROUND Rituximab has provided a revolutionary contribution to the treatment of B-cell non-Hodgkins lymphomas (NHL). A high prevalence of hepatitis C virus (HCV) infection has been described in B-cell NHL patients. Cases of liver dysfunction in HCV-positive patients have been reported with rituximab-containing regimens. AIM to evaluate the liver-related effects of rituximab-containing regimens on HCV-positive CD20-positive B-cell NHL patients. PATIENTS AND METHODS Retrospective analysis of 104 consecutive patients. HCV status was determined, and development of hepatitis flares analysed. RESULTS Nine patients (8.6%) were HCV-positive. No correlation was shown between viral load and alanine transaminase levels. Three of the 9 HCV-positive, and none of the 95 HCV-negative developed hepatitis flares (p<0.001). At the 12-month follow-up hepatitis flare patients were alive and in remission for their haematological disease and no hepatitis flares, liver-related death had developed. CONCLUSIONS HCV-positive status may represent a risk factor for the development of hepatic flares in B-cell NHL patients receiving rituximab-containing regimens. Despite the increase in liver function tests, there were no major clinical events.

Somatostatin Receptor Localization of Pancreatic Endocrine Tumors

Abstract. Gastroenteropancreatic endocrine tumors are difficult to localize. At the same time the tumor is localized, though, there is an opportunity for cure or to remove tumor tissue. In this study we have prospectively examined the ability of 111 In-octreotide scintigraphy, magnetic resonance imaging (MRI), and computed tomography (CT) to localize tumor lesions in 24 patients with a biochemical or histologic diagnosis of neuroendocrine tumor. In eight patients a surgical assessment of the imaging results was prospectively performed. Planar and abdominal single-photon emission tomography (SPET) images acquired 4 and 24 hours after 180 to 220 MBq of 111 In-octreotide injection were evaluated and compared with conventional imaging techniques. SPET scintigraphy visualized more presumed tumor lesions (n = 39) than conventional imaging studies (MRI,n = 25; CT,n = 13); 23 of 24 patients had positive octreotide scintigraphy, 17 of 24 had positive MRI-scans, and 12 of 24 patients had positive CT scans. It was concluded that 111In-octreotide scintigraphy combined with conventional imaging improves the preoperative localization of presumably tumorous lesions in patients with gastroenterohepatic endocrine tumors.

Long-term octreotide treatment of metastatic carcinoid tumor

The optimal dosage of somatostatin analogs for the long-term control of carcinoid tumors has not yet been established. Receptor alterations induced during long term treatment with somatostatin analogs have lead to consecutive drug dosage increases in order to control carcinoid disease. In this report, we describe the rapid and effective control of tumor in a patient with metastatic carcinoid treated for nine years with a single daily dose of octreotide based on tumor marker levels. Tumoral somatostatin receptor (sst) subtype analysis by RT-PCR amplification showed the expression of sst2 subtype only. We suggest that a single daily dose of octreotide strictly related to tumor marker secretion, could have played a role in the effective long-term therapy by avoiding the phenomenon of somatostatin receptor desensitisation. Furthermore, the exclusive presence of sst2 subtype supports the high affinity of octreotide to tumoral cells.

Progression of gastric enterochromaffin-like cells growth in Zollinger-Ellison syndrome and atrophic body gastritis patients

BACKGROUND Enterochromaffin-like cell hyperplasia of the gastric body mucosa occurs in hypergastrinaemic conditions such as atrophic body gastritis and Zollinger-Ellison syndrome. However, the time course of change or factors involved are not known. AIMS To compare the rate of change of enterochromaffin-like cell proliferation in patients with atrophic body gastritis and Zollinger-Ellison syndrome. PATIENTS From a consecutive series of atrophic body gastritis and Zollinger-Ellison syndrome patients, studied at the time of first diagnosis, 10 atrophic body gastritis (4 with pernicious anaemia) and 14 Zollinger-Ellison syndrome (4 with multiple endocrine neoplasia type 1) patients were followed-up for a median time of 48 months. METHODS At entry and during follow-up patients underwent: plasma gastrin determination, endoscopic sampling of body mucosa for qualitative assessment of enterochromaffin-like cell hyperplasia pattern and degree of glandular atrophy, qualitative and morphometric analyses of body mucosa endocrine cells. RESULTS At time of diagnosis, enterochromaffin-like cell lesions were more severe in atrophic body gastritis than in Zollinger-Ellison syndrome. During follow-up, no significant variations were observed in gastrin values, enterochromaffin-like cell patterns and grade of body mucosa atrophy in atrophic body gastritis. In contrast, gastrin levels were significantly increased [median 1200 (235-2625) vs 1947 (225-5200) pg/ml; p<0.001)] as was total volume density of enterochromaffin-like cells [median 1.60 (0.53-4.06) vs 3.18 (1.35-21.13)% of mucosal epithelial component; (p<0.005)] in Zollinger-Ellison syndrome. Micronodular hyperplasia of enterochromaffin-like cells, present in only one patient at diagnosis, was observed in 8 Zollinger-Ellison syndrome patients at follow-up. CONCLUSIONS These data suggest that the progression of enterochromaffin-like cell growth in human gastric mucosa requires an increase of and/or a prolonged exposure to severe hypergastrinaemia.