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World Journal of Gastroenterology Sep 2021Zollinger-Ellison syndrome (ZES) associated with pancreatic or duodenal gastrinoma is characterized by gastric acid hypersecretion, which typically leads to... (Review)
Review
Zollinger-Ellison syndrome (ZES) associated with pancreatic or duodenal gastrinoma is characterized by gastric acid hypersecretion, which typically leads to gastroesophageal reflux disease, recurrent peptic ulcers, and chronic diarrhea. As symptoms of ZES are nonspecific and overlap with other gastrointestinal disorders, the diagnosis is often delayed with an average time between the onset of symptoms and final diagnosis longer than 5 years. The critical step for the diagnosis of ZES is represented by the initial clinical suspicion. Hypergastrinemia is the hallmark of ZES; however, hypergastrinemia might recognize several causes, which should be ruled out in order to make a final diagnosis. Gastrin levels > 1000 pg/mL and a gastric pH below 2 are considered to be diagnostic for gastrinoma; some specific tests, including esophageal pH-recording and secretin test, might be useful in selected cases, although they are not widely available. Endoscopic ultrasound is very useful for the diagnosis and the local staging of the primary tumor in patients with ZES, particularly in the setting of multiple endocrine neoplasia type 1. Some controversies about the management of these tumors also exist. For the localized stage, the combination of proton pump inhibitory therapy, which usually resolves symptoms, and surgery, whenever feasible, with curative intent represents the hallmark of gastrinoma treatment. The high expression of somatostatin receptors in gastrinomas makes them highly responsive to somatostatin analogs, supporting their use as anti-proliferative agents in patients not amenable to surgical cure. Other medical options for advanced disease are super-imposable to other neuroendocrine neoplasms, and studies specifically focused on gastrinomas only are scant and often limited to case reports or small retrospective series. The multidisciplinary approach remains the cornerstone for the proper management of this composite disease. Herein, we reviewed available literature about gastrinoma-associated ZES with a specific focus on differential diagnosis, providing potential diagnostic and therapeutic algorithms.
Topics: Gastrinoma; Humans; Multiple Endocrine Neoplasia Type 1; Pancreatic Neoplasms; Retrospective Studies; Zollinger-Ellison Syndrome
PubMed: 34629807
DOI: 10.3748/wjg.v27.i35.5890 -
World Journal of Gastroenterology Oct 2012In the present paper the increasing difficulty of diagnosis of Zollinger-Ellison syndrome (ZES) due to issues raised in two recent papers is discussed. These issues... (Review)
Review
In the present paper the increasing difficulty of diagnosis of Zollinger-Ellison syndrome (ZES) due to issues raised in two recent papers is discussed. These issues involve the difficulty and need to withdraw patients suspected of ZES from treatment with Proton Pump Inhibitors (omeprazole, esomeprazole, lansoprazole, rabeprazole, pantoprazole) and the unreliability of many gastrin radioimmunoassays. The clinical context of each of these important issues is reviewed and the conclusions in these articles commented from the perspective of clinical management.
Topics: Contraindications; Gastrins; Humans; Proton Pump Inhibitors; Zollinger-Ellison Syndrome
PubMed: 23112541
DOI: 10.3748/wjg.v18.i39.5495 -
International Journal of Endocrine... 2017In recent years the diagnosis of Zollinger-Ellison syndrome (ZES) has become increasingly controversial with several new approaches and criteria proposed, differing from...
In recent years the diagnosis of Zollinger-Ellison syndrome (ZES) has become increasingly controversial with several new approaches and criteria proposed, differing from the classical biochemical criterion of inappropriate hypergastrinemia (i.e., hypergastrinemia in the presence of hyperchlorhydria) (Table 1). These changes have come about because of the difficulty and potential dangers of stopping proton pump inhibitors (PPIs) for gastric acid analysis; the recognition than many of the current assays used to assess gastrin concentrations are unreliable; the development of sensitive imaging modalities that detect neuroendocrine tumors (NETs) including an increasing number of the primary gastrinomas; the increased use of percutaneous or endoscopic ultrasound (EUS)-directed biopsies/cytology and the general lack of availability of acid secretory testing. In this article we will discuss the basis for these controversies, review the proposed changes in diagnostic approaches and make recommendations for supporting the diagnosis of ZES in the modern era.
PubMed: 29326808
DOI: 10.2217/ije-2017-0018 -
Endocrinology and Metabolism Clinics of... Sep 2018This article reviews the role of surgical and medical management in patients with Zollinger-Ellison syndrome (ZES) due to a gastrin-secreting neuroendocrine tumor... (Review)
Review
This article reviews the role of surgical and medical management in patients with Zollinger-Ellison syndrome (ZES) due to a gastrin-secreting neuroendocrine tumor (gastrinoma). It concentrates on the status at present but also briefly reviews the changes over time in treatment approaches. Generally, surgical and medical therapy are complementary today; however, in some cases, such as patients with ZES and multiple endocrine neoplasia type 1, the treatment approach remains controversial.
Topics: Gastrinoma; Humans; Multiple Endocrine Neoplasia Type 1; Neuroendocrine Tumors; Stomach Neoplasms; Zollinger-Ellison Syndrome
PubMed: 30098717
DOI: 10.1016/j.ecl.2018.04.009 -
International Journal of Molecular... Oct 2019The use of proton pump inhibitors (PPIs) over the last 30 years has rapidly increased both in the United States and worldwide. PPIs are not only very widely used both... (Review)
Review
The use of proton pump inhibitors (PPIs) over the last 30 years has rapidly increased both in the United States and worldwide. PPIs are not only very widely used both for approved indications (peptic ulcer disease, gastroesophageal reflux disease (GERD), Helicobacter pylori eradication regimens, stress ulcer prevention), but are also one of the most frequently off-label used drugs (25-70% of total). An increasing number of patients with moderate to advanced gastroesophageal reflux disease are remaining on PPI indefinitely. Whereas numerous studies show PPIs remain effective and safe, most of these studies are <5 years of duration and little data exist for >10 years of treatment. Recently, based primarily on observational/epidemiological studies, there have been an increasing number of reports raising issues about safety and side-effects with very long-term chronic treatment. Some of these safety issues are related to the possible long-term effects of chronic hypergastrinemia, which occurs in all patients taking chronic PPIs, others are related to the hypo-/achlorhydria that frequently occurs with chronic PPI treatment, and in others the mechanisms are unclear. These issues have raised considerable controversy in large part because of lack of long-term PPI treatment data (>10-20 years). Zollinger-Ellison syndrome (ZES) is caused by ectopic secretion of gastrin from a neuroendocrine tumor resulting in severe acid hypersecretion requiring life-long antisecretory treatment with PPIs, which are the drugs of choice. Because in <30% of patients with ZES, a long-term cure is not possible, these patients have life-long hypergastrinemia and require life-long treatment with PPIs. Therefore, ZES patients have been proposed as a good model of the long-term effects of hypergastrinemia in man as well as the effects/side-effects of very long-term PPI treatment. In this article, the insights from studies on ZES into these controversial issues with pertinence to chronic PPI use in non-ZES patients is reviewed, primarily concentrating on data from the prospective long-term studies of ZES patients at NIH.
Topics: Animals; Carcinoma, Neuroendocrine; Chronic Disease; Gastrinoma; Gastrins; Humans; Proton Pump Inhibitors; Risk Factors; Stomach Diseases; Time Factors; Treatment Outcome; Zollinger-Ellison Syndrome
PubMed: 31623145
DOI: 10.3390/ijms20205128 -
Current Opinion in Gastroenterology Nov 2013To review the recent advances and current controversies in patients with Zollinger-Ellison syndrome (ZES). (Review)
Review
PURPOSE OF REVIEW
To review the recent advances and current controversies in patients with Zollinger-Ellison syndrome (ZES).
RECENT FINDINGS
Recent advances in the management of ZES include: improved understanding of the pathogenesis of gastrinoma and pancreatic neuroendocrine tumors, new prognostic classification systems, new diagnostic algorithms, more sensitive localization studies, new treatment strategies including improved control of gastric acid secretion and role for surgery, and new approaches to patients with advanced disease. Controversies include: the best approach to a patient with hypergastrinemia suspected of possibly having ZES, the appropriate gastrin assay to use, the role of surgery in patients with ZES, especially those with multiple endocrine neoplasia type 1, and the precise order of therapeutic modalities in the treatment of patients with advanced disease.
SUMMARY
This review updates clinicians regarding important advances and controversies required to optimally diagnose and manage patients with ZES.
Topics: Diagnosis, Differential; Gastric Acid; Gastrinoma; Humans; Pancreatic Neoplasms; Zollinger-Ellison Syndrome
PubMed: 24100728
DOI: 10.1097/MOG.0b013e328365efb1 -
CMAJ : Canadian Medical Association... Dec 2019
Topics: Adult; Duodenum; Endoscopy, Digestive System; Humans; Male; Stomach; Zollinger-Ellison Syndrome
PubMed: 31818929
DOI: 10.1503/cmaj.191047 -
Medicine May 2013Multiple endocrine neoplasia type 1 (MEN1) is classically characterized by the development of functional or nonfunctional hyperplasia or tumors in endocrine tissues... (Comparative Study)
Comparative Study
Causes of death and prognostic factors in multiple endocrine neoplasia type 1: a prospective study: comparison of 106 MEN1/Zollinger-Ellison syndrome patients with 1613 literature MEN1 patients with or without pancreatic endocrine tumors.
Multiple endocrine neoplasia type 1 (MEN1) is classically characterized by the development of functional or nonfunctional hyperplasia or tumors in endocrine tissues (parathyroid, pancreas, pituitary, adrenal). Because effective treatments have been developed for the hormone excess state, which was a major cause of death in these patients in the past, coupled with the recognition that nonendocrine tumors increasingly develop late in the disease course, the natural history of the disease has changed. An understanding of the current causes of death is important to tailor treatment for these patients and to help identify prognostic factors; however, it is generally lacking.To add to our understanding, we conducted a detailed analysis of the causes of death and prognostic factors from a prospective long-term National Institutes of Health (NIH) study of 106 MEN1 patients with pancreatic endocrine tumors with Zollinger-Ellison syndrome (MEN1/ZES patients) and compared our results to those from the pooled literature data of 227 patients with MEN1 with pancreatic endocrine tumors (MEN1/PET patients) reported in case reports or small series, and to 1386 patients reported in large MEN1 literature series. In the NIH series over a mean follow-up of 24.5 years, 24 (23%) patients died (14 MEN1-related and 10 non-MEN1-related deaths). Comparing the causes of death with the results from the 227 patients in the pooled literature series, we found that no patients died of acute complications due to acid hypersecretion, and 8%-14% died of other hormone excess causes, which is similar to the results in 10 large MEN1 literature series published since 1995. In the 2 series (the NIH and pooled literature series), two-thirds of patients died from an MEN1-related cause and one-third from a non-MEN1-related cause, which agrees with the mean values reported in 10 large MEN1 series in the literature, although in the literature the causes of death varied widely. In the NIH and pooled literature series, the main causes of MEN1-related deaths were due to the malignant nature of the PETs, followed by the malignant nature of thymic carcinoid tumors. These results differ from the results of a number of the literature series, especially those reported before the 1990s. The causes of non-MEN1-related death for the 2 series, in decreasing frequency, were cardiovascular disease, other nonendocrine tumors > lung diseases, cerebrovascular diseases. The most frequent non-MEN1-related tumor deaths were colorectal, renal > lung > breast, oropharyngeal. Although both overall and disease-related survival are better than in the past (30-yr survival of NIH series: 82% overall, 88% disease-related), the mean age at death was 55 years, which is younger than expected for the general population.Detailed analysis of causes of death correlated with clinical, laboratory, and tumor characteristics of patients in the 2 series allowed identification of a number of prognostic factors. Poor prognostic factors included higher fasting gastrin levels, presence of other functional hormonal syndromes, need for >3 parathyroidectomies, presence of liver metastases or distant metastases, aggressive PET growth, large PETs, or the development of new lesions.The results of this study have helped define the causes of death of MEN1 patients at present, and have enabled us to identify a number of prognostic factors that should be helpful in tailoring treatment for these patients for both short- and long-term management, as well as in directing research efforts to better define the natural history of the disease and the most important factors determining long-term survival at present.
Topics: Adult; Aged; Aged, 80 and over; Cause of Death; Female; Humans; Male; Middle Aged; Multiple Endocrine Neoplasia Type 1; Mutation; Pancreatic Neoplasms; Prognosis; Prospective Studies; Proto-Oncogene Proteins; United States; Young Adult; Zollinger-Ellison Syndrome
PubMed: 23645327
DOI: 10.1097/MD.0b013e3182954af1