Presentation, Diagnosis, and Treatment of a Sporadic Gastrinoma With Liver Metastases.

A gastrinoma is a rare and potentially deadly tumor. Gastrinomas can be difficult to detect at first, given that affected patients can present with nonspecific symptoms, such as anemia, weight loss, and diarrhea, leading to a large list of differentials. The symptoms can be hard to manage, and the treatment almost always includes surgical intervention. Gastrinomas often metastasize to the liver, in which case, the only curative treatment option is surgical resection of the primary tumor along with as many metastatic lesions as possible. This report reviews the case of a 59-year-old female who presented with symptoms of anemia and an upper gastrointestinal bleed, who was discovered to have a pancreatic gastrinoma with more than 12 liver metastases. It also describes the management of her critical condition, which was used to give her the best chance of survival.

Middle-segment preserving pancreatectomy: a literature review and case report.

PURPOSE: Middle segment-preserving pancreatectomy (MSPP) is a relatively new parenchymal-sparing surgery that has been introduced as an alternative to total pancreatectomy (TP) for multicentric benign and borderline pancreatic diseases. To date, only 36 cases have been reported in English. METHODS: We reviewed 22 published articles on MSPP and reported an additional case. RESULTS: Our patient was a 49-year-old Japanese man diagnosed with Zollinger-Elison syndrome (ZES) caused by duodenal and pancreatic gastrinoma associated with multiple endocrine neoplasia syndrome type 1. We avoided TP and chose MSPP as the operative technique due to his relatively young age. The patient developed a grade B postoperative pancreatic fistula (POPF), which improved with conservative treatment. He was discharged without further treatment. To date, no tumor has recurred, and pancreatic function seems to be maintained. According to a literature review, the morbidity rate of MSPP is as high as 54%, mainly due to the high incidence of POPF (32%). In contrast, there was no perioperative mortality, and postoperative pancreatic function was comparable to that after conventional pancreatectomy. CONCLUSIONS: Despite the high incidence of POPF, MSPP appears to be safe, with low perioperative mortality and good postoperative pancreatic sufficiency.

Diagnostics and Imaging for Pancreatic Neuroendocrine Tumors.

Pancreatic neuroendocrine tumors originate from hormone-producing islet cells and have a propensity to metastasize to the liver once they reach 2 cm in size. Their diagnosis relies upon a combination of computed tomography, MRI, DOTATATE PET, and endoscopic ultrasound with or without tissue biopsy. Biochemical work-up is driven by patient symptoms of hormone excess.

A Case of a Metastatic Pancreatic Neuroendocrine Tumor: A Surgical Conundrum Wrapped in Functionality's Embrace.

This case study reports a rare case of a non-functioning metastatic pancreatic neuroendocrine tumor (pNET) transforming into a functioning pNET. A 59-year-old male, previously treated with distal pancreatectomy, splenectomy, lymph node dissection, liver metastasectomy, and pharmacotherapy, presented with weakness, hypoglycemia, and daily episodes of watery diarrhea. A functioning neuroendocrine liver metastasis expressing insulin and gastrin was identified. Surgical intervention, including left lateral hepatectomy and microwave ablation of multiple intrahepatic lesions, resulted in symptom resolution and uneventful recovery. However, metastatic liver disease re-emerged seven months post-surgery, necessitating chemotherapy. This case highlights the importance of vigilance for symptom development in non-functioning pNETs, signaling potential disease relapse and phenotype transformation, and suggests surgical treatment as a viable option in select cases.

Sporadic gastrinoma with refractory benign esophageal stricture: A case report.

BACKGROUND: Gastrinoma is characterized by an excessive release of gastrin, leading to hypersecretion of gastric acid, subsequently resulting in recurrent peptic ulcers, chronic diarrhea, and even esophageal strictures. This case report aims to improve awareness and facilitate early diagnosis and treatment of gastrinoma by presenting a rare case of gastrinoma with refractory benign esophageal stricture (RBES). Additionally, it highlights the persistent challenges that gastroenterologists encounter in managing RBES. CASE SUMMARY: This case demonstrates a patient with gastrinoma who developed RBES and complete esophageal obstruction despite management with maximal acid suppressive therapy, multiple endoscopic bougie dilations and endoscopic incisional therapy (EIT). CONCLUSION: It is essential to diagnose gastrinoma as early as possible, as inadequately controlled acid secretion over an extended period increases the risk of developing severe esophageal strictures. In patients with esophageal strictures causing complete luminal obstruction, blind reopening EIT presents challenges and carries a high risk of perforation.

Sporadic Zollinger-Ellison syndrome in a patient with isolated mesenteric gastrinoma.

INTRODUCTION: Zollinger-Ellison syndrome (ZES) is due to a gastrin-producing neuroendocrine tumor (gastrinoma) with subsequent gastric acid hypersecretion, gastroesophageal reflux disease (GERD), peptic ulcers, and chronic diarrhea. CASE PRESENTATION: A 40-year old patient presented with epigastric pain associated with diarrhea evolving for 10 years, he has been treated by acid-suppressive medications without substantial clinical improvement. Gastro-duodenal endoscopy was performed with gastric biopsies that showed peptic ulcerations, a serum gastrin assay that showed high levels exceeding 10 times the upper limit of the normal range. The abdominal contrast-enhanced computed tomography scan (CT-Scan) showed a solid-cystic mass with contrast enhancement in the right colon mesentery. The histopathological analysis of the resected mass showed a well-differentiated neuroendocrine tumor, and the diagnosis of a sporadic Zollinger-Ellison syndrome (ZES) was disclosed. Eighteen months after the surgical treatment the patient has no symptoms of the disease. CLINICAL DISCUSSION: Patients with ZES present often with long-standing clinical symptoms with delayed diagnosis. The surgical resection of the causative gastrinoma remains the most effective therapeutic treatment. CONCLUSION: Patients with refractory chronic diarrhea and epigastric pain should be suspected of having ZES in order to benefit from adequate clinical management.

The cckOMA syndrome and its relation to the Zollinger-Ellison syndrome: a diagnostic challenge.

OBJECTIVE: Among patients with enteropancreatic neuroendocrine tumor syndromes only one case with a cholecystokinin (CCK) secreting tumor has been reported. She had significant hyperCCKemia leading to a specific syndrome of severe diarrheas, weight loss, repeated duodenal ulcers and a permanently contracted gallbladder with gallstones. There are, however, reasons to believe that further CCKomas exist, for instance among Zollinger-Ellison patients with normal plasma gastrin concentrations. The present review is a call to gastroenterologists for awareness of such CCKoma patients. METHOD: After a short case report, the normal endocrine and oncological biology of CCK is described. Subsequently, the CCKoma symptoms are discussed with particular reference to the partly overlapping symptoms of the Zollinger-Ellison syndrome. In this context, the diagnostic use of truly specific CCK and gastrin assays are emphasized. The discussion also entails the problem of access to accurate CCK measurements. CONCLUSION: Obviously, the clinical awareness about the CCKoma syndrome is limited. Moreover, it is also likely that the knowledge about the necessary specificity demands of diagnostic gastrin and CCK assays have obscured proper diagnosis of the CCKoma syndromes in man.

Spatial profiling reveals tissue-specific neuro-immune interactions in gastroenteropancreatic neuroendocrine tumors.

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are heterogeneous malignancies that arise from complex cellular interactions within the tissue microenvironment. Here, we sought to decipher tumor-derived signals from the surrounding microenvironment by applying digital spatial profiling (DSP) to hormone-secreting and non-functional GEP-NETs. By combining this approach with in vitro studies of human-derived organoids, we demonstrated the convergence of cell autonomous immune and pro-inflammatory proteins that suggests their role in neuroendocrine differentiation and tumorigenesis. DSP was used to evaluate the expression of 40 neural- and immune-related proteins in surgically resected duodenal and pancreatic NETs (n = 20) primarily consisting of gastrinomas (18/20). A total of 279 regions of interest were examined between tumors, adjacent normal and abnormal-appearing epithelium, and the surrounding stroma. The results were stratified by tissue type and multiple endocrine neoplasia I (MEN1) status, whereas protein expression was validated by immunohistochemistry (IHC). A tumor immune cell autonomous inflammatory signature was further evaluated by IHC and RNAscope, while functional pro-inflammatory signaling was confirmed using patient-derived duodenal organoids. Gastrin-secreting and non-functional pancreatic NETs showed a higher abundance of immune cell markers and immune infiltrate compared with duodenal gastrinomas. Compared with non-MEN1 tumors, MEN1 gastrinomas and preneoplastic lesions showed strong immune exclusion and upregulated expression of neuropathological proteins. Despite a paucity of immune cells, duodenal gastrinomas expressed the pro-inflammatory and pro-neural factor IL-17B. Treatment of human duodenal organoids with IL-17B activated NF-κB and STAT3 signaling and induced the expression of neuroendocrine markers. In conclusion, multiplexed spatial protein analysis identified tissue-specific neuro-immune signatures in GEP-NETs. Duodenal gastrinomas are characterized by an immunologically cold microenvironment that permits cellular reprogramming and neoplastic transformation of the preneoplastic epithelium. Moreover, duodenal gastrinomas cell autonomously express immune and pro-inflammatory factors, including tumor-derived IL-17B, that stimulate the neuroendocrine phenotype. © 2024 The Pathological Society of Great Britain and Ireland.

Management of Gastric Neuroendocrine Tumors: A Review.

Gastric neuroendocrine tumors (G-NET) are rare tumors arising from enterochromaffin-like cells of the gastric mucosa. They belong to a larger group called gastroenteropancreatic neuroendocrine tumors and are classified as low, intermediate, or high-grade tumors based on their proliferative indices. They are further categorized into three subtypes based on their morphologic characteristics, pathogenesis, and behavior. Types 1 and 2 tumors are characterized by elevated serum gastrin and are usually multifocal. They typically occur in the setting of atrophic gastritis or MEN1/Zollinger Ellison syndrome, respectively. Type 2 tumors are associated with the most symptoms, such as abdominal pain and diarrhea. Type 3 tumors are associated with normal serum gastrin, are usually solitary, and occur sporadically. This type has the most aggressive phenotype and metastatic potential. Treatment and prognosis for G-NET is dependent on their type, size, and stage. Type 1 has the best prognosis, and Type 3 has the worst. This review discusses the presentation, workup, and surgical management of these tumors.

Severe esophageal stricture after perforation and necrotizing esophagitis: unusual presentation of a duodenal gastrinoma.

Gastrinomas are pancreatic or duodenal endocrine tumors that secrete excess gastrin, which causes gastroesophageal reflux disease, peptic ulcers, and chronic diarrhea. Due to the rarity of the disease, nonspecific symptoms, and the outstanding effect of proton pump inhibitors, diagnosing gastrinomas is difficult. Here, we present the case of a 58-year-old woman who had a duodenal gastrinoma that caused rare but critical events, including esophageal perforation, necrotizing esophagitis, and severe esophageal stricture. She presented with a non-malignant severe lower esophageal stricture, which was resistant to endoscopic dilatation. During esophagectomy, a duodenal mass was excised and diagnosed as gastrinoma. This was considered the main cause of all events. Gastrinomas are rarely encountered in clinical practice, but early diagnosis is necessary to avoid serious conditions. Therefore, whenever we encounter a patient with gastroesophageal reflux disease requiring long-term treatment or is refractory, we must not forget to screen for gastrinomas.

Esophageal Perforation Unveiling the Diagnosis of Zollinger-Ellison Syndrome.

Gastrinomas are the most common neuroendocrine tumors worldwide and cause a clinical syndrome known as Zollinger-Ellison Syndrome (ZES). Increased acid production resulting from elevated gastrin levels contributes to symptoms such as abdominal pain, heartburn, and diarrhea. However, the non-specificity and overlap in the symptoms with idiopathic peptic ulcer disease and gastroesophageal reflux disease (GERD) can lead to delayed diagnosis. In this case, we describe a patient with a past medical history of GERD and a perforated gastric ulcer who continued to experience symptoms of dyspepsia and had a subsequent esophageal perforation, despite H. pylori eradication and high-dose proton pump inhibitor (PPI) therapy. Multiple ulcers were visualized in the first portion of the duodenum, and metastatic lesions were demonstrable in the liver. Serum gastrin level was elevated to 433 pg/mL. Histology of liver biopsy showed a well-differentiated neuroendocrine tumor, supporting the diagnosis of ZES. This article underscores the significance of considering ZES in the differential in cases of refractory gastric hyperacidity and the importance of early diagnosis with serum gastrin testing to prevent complications such as gastric obstruction, perforation, hemorrhage, esophageal strictures, or rupture and to minimize the risk of metastasis. It is noteworthy that while perforations in cases of ZES typically occur in the duodenum, this particular case is atypical as it had involved the stomach. Furthermore, it was associated with esophageal perforation, likely resulting from forceful and prolonged vomiting caused by persistent dyspepsia.

Ectopic Adrenocorticotropic Hormone-Producing Metastatic Gastrinoma: A Case Report.

Pancreatic neuroendocrine tumors secreting gastrin and adrenocorticotropic hormone (ACTH) are rare. The presentation of the cases can be varied, making the diagnosis challenging and often delayed. Here, we present a patient who presented with severe hypokalemia and was found to have ectopic Cushing's syndrome. An abdominal CT scan showed a pancreatic lesion with metastatic liver disease. A biopsy of the liver lesion confirmed a metastatic neuroendocrine tumor. The final diagnosis was ectopic ACTH-producing metastatic gastrinoma. Twenty-four-hour urinary cortisol was significantly elevated at 9,790 mcg/24 hours. The excess hormonal secretion was successfully treated with ketoconazole and somatostatin analogs. She was further started on chemotherapy with capecitabine plus temozolomide, which has become the preferred chemotherapy treatment after the results of the recently completed trial. She also received Y90 therapy for metastatic liver disease. The prognosis of metastatic pancreatic neuroendocrine tumors is poor. Multidisciplinary combined therapies can help control disease and improve prognosis. We present an 18-month-long patient follow-up and a literature review of ectopic ACTH-producing metastatic gastrinomas.

A Rare Case of Hepatic Gastrinoma.

Zollinger-Ellison syndrome (ZES) is a rare condition caused by gastrin-secreting neuroendocrine tumors known as gastrinomas. We present a case of hepatic ZES presenting as upper gastrointestinal (GI) bleeding in a 70-year-old female. Initial evaluation revealed the patient to be in severe sepsis with septic shock secondary to a urinary tract infection, and her hospitalization was complicated by hematemesis and melena in the setting of multiple duodenal ulcers. Subsequent investigations, including elevated gastrin levels and a somatostatin receptor scan, confirmed the diagnosis of gastrinoma.

Typical Zollinger-Ellison syndrome-atypical location of gastrinoma and absence of hypergastrinemia: A case report and review of literature.

BACKGROUND: Zollinger-Ellison syndrome (ZES) results from hypersecretion of gastrin from pancreatic or duodenal neuroendocrine tumors, commonly referred to as gastrinomas. The high levels of gastrin lead to a typical presentation involving watery diarrhea and multiple ulcers in the duodenum. Here, we have presented the rare case of a patient with ZES and absence of hypergastrinemia as well as an atypical location of gastrinoma. CASE SUMMARY: A 72-year-old woman presented with the typical clinical manifestations of ZES, including upper abdominal pain, significant watery diarrhea, and acidic liquid vomitus. Surprisingly, however, she did not have an increased level of serum gastrin. In addition, there was no evidence of gastrinoma or any other ulcerogenic tumor. Esophagogastroduodenoscopy was conducted to examine the upper digestive tract. Revised diagnoses were considered, and an individualized treatment plan was developed. The patient responded to antacid medication while experiencing intermittent, recurring bouts of ZES. 18F-AlF-NOTA-octreotide positron emission tomography (18F-OC PET)/computed tomography (CT) helped locate the tumor. Postoperative pathology and immunohistochemistry results suggested that the tumor was a gastrinoma located at an unconventional site. CONCLUSION: This present case study demonstrates the possibility of ZES-like manifestation in patients with absence of hypergastrinemia. 18F-OC PET/CT is a relatively new imaging technique that can be applied for diagnosing even tiny gastrinomas that are atypical in terms of location.

Management Dilemma: Is Enucleation With Lymphadenectomy a Viable Choice for Large Pancreatic Neuroendocrine Tumors (p-NETs)?

Managing pancreatic neuroendocrine tumors (pNETs) has gradually taken a trend toward conservative management owing to its slow-growing and prolonged course. Though clear criteria exist regarding managing small tumors, the direction of a large tumor remains a dilemma. We present a case of a young 26-year-old lactating woman with a large 3.4 cm × 3.2 cm mass in the uncinate process, which is adjacent to the inferior vena cava (IVC) and has flimsy adhesions to the duodenum. She also had an enhancing adjacent lymph node measuring 1.2 cm × 0.7 cm, which showed enhancement with Ga-68 DOTANOC positron emission tomography/computed tomography (PET/CT) and raised serum gastrin levels. The dilemma was between pancreaticoduodenectomy (PD) or enucleation with lymphadenectomy (EL). Finally, EL was conducted. We discussed this case with relevant studies, which we had referred to because large-sized tumors are not usually enucleated.

Establishment of a reference interval for 12-hour fasted serum gastrin concentration in adult dogs.

BACKGROUND: Adherence to traditional 24-h fasting periods for serum gastrin concentration in dogs can be challenging and may delay the institution of therapies for suspected hypergastrinemia. Peer-reviewed publications regarding serum gastrin reference intervals (RI) are lacking. Hypercalcemia is associated with hypergastrinemia in people; limited data exist in dogs. OBJECTIVE: The objective of the study was to generate a RI for a 12-h fasted serum gastrin concentration in dogs and to investigate whether correlations exist with age, weight, sex, and total calcium concentration. METHODS: Fifty-five healthy adult dogs (>1 year of age). The screening included: medical history, physical examination, CBC (15 dogs), and serum chemistry (55 dogs). Gastrin was measured via a commercial radioimmunoassay. The RI for 12-h fasted serum gastrin concentration was calculated according to the recommendations of the American Society for Veterinary Clinical Pathology. Additionally, data were evaluated for correlation with selected variables. RESULTS: The RI for serum gastrin following a 12-h fasting period was 15.1-78.9 ng/L with 90% confidence intervals for the lower and upper limits of 14.0-22.9 and 68.3-83.0 ng/L, respectively. A generalized linear model did not detect significant relationships between gastrin and age (P = 0.48), sex (P = 0.30), weight (P = 0.93), or total calcium concentration (P = 0.84). CONCLUSIONS: A 12-h fasted serum gastrin concentration RI has been established. Given the limited range of serum calcium concentrations in our healthy study population, additional investigations are needed to determine the effects of hypercalcemia on serum gastrin concentrations in dogs and for any potential clinical consequences thereof.

European Neuroendocrine Tumor Society 2023 guidance paper for functioning pancreatic neuroendocrine tumour syndromes.

This ENETS guidance paper aims to provide practical advice to clinicians for the diagnosis, treatment and follow-up of functioning syndromes in pancreatic neuroendocrine tumours (NET). A NET-associated functioning syndrome is defined by the presence of a clinical syndrome combined with biochemical evidence of inappropriately elevated hormonal levels. Different hormonal syndromes can be encountered in pancreatic NET patients, including insulinoma, gastrinoma as well as the rare glucagonoma, VIPoma, ACTHoma, PTHrPoma, carcinoid syndrome, calcitoninoma, GHRHoma and somatostatinoma. The recommendations provided in this paper focus on the biochemical, genetic and imaging work-up as well as therapeutic management of the individual hormonal syndromes in well-differentiated, grade 1-3, functioning NET with the primary tumour originating in the pancreas, and for specific subtypes also in the duodenum.

Gastrinoma With Relatively Low Gastrin Levels: A Case Report.

Gastrinomas can often be cured with surgical removal if detected early enough. We present a case report where a patient was diagnosed with gastrinoma with relatively low serum gastrin levels after subsequent duodenojejunostomy, gastrojejunostomy, total gastrectomy, and cholecystectomy. With this case report, we hope to promote a higher level of awareness of pancreatic neuroendocrine (NE) tumors and educate clinicians on the full effects of proton pump inhibitor (PPI) use on patient workup, diagnostics, and care.

Effective strategies for adequate control of hormonal secretion in functioning neuroendocrine neoplasms.

Neuroendocrine neoplasms are a unique form of malignancies as they can be accompanied by specific functioning hormonal syndromes that can impair survival and quality of life in patients. Functioning syndromes are defined by the combination of specific clinical signs and symptoms in combination with inappropriately elevated circulating levels of hormones. Clinicians should remain vigilant for the presence of functioning syndromes in neuroendocrine neoplasm patients at presentation as well as during follow-up. The correct diagnostic work-up should be initiated in cases of clinical suspicion of a neuroendocrine neoplasm-associated functioning syndrome. Management of a functional syndrome includes options from supportive, surgical, hormonal and antiproliferative treatment modalities. Here, we review the patient and tumour characteristics for each functioning syndrome that should be taken into account when deciding the optimum treatment strategy in neuroendocrine neoplasm patients.