Neoadjuvant Peptide Receptor Radionuclide Therapy in a Rare Case of Pediatric Primary Hepatic Gastrinoma.

ABSTRACT: Gastrinomas with predilection for the adult male population are located in the gastrinoma triangle (>90%). Primary hepatic gastrinoma especially in pediatric population is very rare. Peptide receptor radionuclide therapy has shown benefit in metastatic gastroenteropancreatic neuroendocrine tumors (NETs) with an increasing interest in expanding its role as neoadjuvant treatment modality to improve the surgical candidature in inoperable NETs. There is currently no literature supporting its role in the pediatric NET patients. We present a rare case of a young boy with primary hepatic gastrinoma where 177Lu-based peptide receptor radionuclide therapy in the neoadjuvant setting contributed to his final disease-free status.

Quantitative characterization of duodenal gastrinoma autofluorescence using multiphoton microscopy.

BACKGROUND: Duodenal gastrinomas (DGASTs) are neuroendocrine tumors that develop in the submucosa of the duodenum and produce the hormone gastrin. Surgical resection of DGASTs is complicated by the small size of these tumors and the tendency for them to develop diffusely in the duodenum. Endoscopic mucosal resection of DGASTs is an increasingly popular method for treating this disease due to its low complication rate but suffers from poor rates of pathologically negative margins. Multiphoton microscopy can capture high-resolution images of biological tissue with contrast generated from endogenous fluorescence (autofluorescence [AF]) through two-photon excited fluorescence (2PEF). Second harmonic generation is another popular method of generating image contrast with multiphoton microscopy (MPM) and is a light-scattering phenomenon that occurs predominantly from structures such as collagen in biological samples. Some molecules that contribute to AF change in abundance from processes related to the cancer disease process (e.g., metabolic changes, oxidative stress, and angiogenesis). STUDY DESIGN/MATERIALS AND METHODS: MPM was used to image 12 separate patient samples of formalin-fixed and paraffin-embedded duodenal gastrinoma slides with a second-harmonic generation (SHG) channel and four 2PEF channels. The excitation and emission profiles of each 2PEF channel were tuned to capture signal dominated by distinct fluorophores with well-characterized fluorescent spectra and known connections to the physiologic changes that arise in cancerous tissue. RESULTS: We found that there was a significant difference in the relative abundance of signal generated in the 2PEF channels for regions of DGASTs in comparison to the neighboring tissues of the duodenum. Data generated from texture feature extraction of the MPM images were used in linear discriminant analysis models to create classifiers for tumor versus all other tissue types before and after principal component analysis (PCA). PCA improved the classifier accuracy and reduced the number of features required to achieve maximum accuracy. The linear discriminant classifier after PCA distinguished between tumor and other tissue types with an accuracy of 90.6%-93.8%. CONCLUSIONS: These results suggest that multiphoton microscopy 2PEF and SHG imaging is a promising label-free method for discriminating between DGASTs and normal duodenal tissue which has implications for future applications of in vivo assessment of resection margins with endoscopic MPM.

Duodenal gastrinoma - case report.

INTRODUCTION: In our text, we want to highlight a rare diagnosis. CASE REPORT: A 54-year-old obese, hypertensive male smoker had been investigated for intermittent abdominal pain for 12 years. The first gastroscopy for a bleeding ulcer was conducted in 2010. In the subsequent years, repeated gastroscopies revealed variable involvement from the esophagus to the duodenum. Capsule enteroscopy did not provide further specification of the diagnosis. The patient underwent colonoscopy and MRI enterography multiple times, with no unequivocal pathological findings. In May 2022, he was admitted to our department for abdominal pain and vomiting. This time, gastroscopy revealed multiple small ulcers in the duodenum and jejunum with clots causing a mechanical obstruction. Chromogranin A was elevated, raising suspicion of gastrinoma. However, somatostatin receptor-based imaging (Octreoscan) was negative. Only the 68Ga-DOTATOC PET (positron emission tomography with the radiopharmaceutical DOTA, labeled with gallium-68) identified a lesion in the subhepatic region, which had no correlation on CT. We concluded the diagnosis as gastrinoma with the Zollinger-Ellison syndrome. Endoscopically, a 1cm tumor was found in the duodenum. In October 2022, the patient underwent an excision of the duodenal wall, and the pathology assessment confirmed our diagnosis of gastrinoma. CONCLUSION: With this case report, we want to emphasize the importance of taking into account neuroendocrine tumors in our differential diagnostic considerations. At the same time, we want to highlight that, according to ESMO recommendations, we should preferentially use 68Ga-DOTATOC PET/CT for the diagnosis instead of scintigraphic examination (111In-Octreoscan).

Primary hepatic gastrinoma, extremely rare case presentation and its surgical resolution, in a third level hospital in Mexico.

The gastrinomas are rare functional neuroendocrine neoplasms, most are localized to the duodenum (70-90%) or the pancreas (2-30%), but less common ectopic sites have been reported. The primary hepatic gastrinoma is extremely rare, with less tan 40 cases reported in the medical literature. Its low incidence and its non specific clinical presentation make it a difficult disease to diagnose. Providing a timely diagnosis the patient can be treated by surgical resection with high chances of success. The objective of this paper is to describe a case of primary hepatic gastrinoma in Mexico, successfully treated by right liver segmentectomy.

Los gastrinomas son neoplasias neuroendocrinas funcionales raras, y la mayoría se localizan en el duodeno (70-90%) o en el páncreas (2-30%), pero también existen otras localizaciones ectópicas poco comunes. El gastrinoma hepático primario es extremadamente raro, con menos de 40 casos reportados en la literatura médica. Su baja incidencia y su presentación clínica inespecífica lo convierten en una enfermedad difícil de diagnosticar. Al realizar un diagnóstico oportuno puede ser tratado mediante resección quirúrgica con altas posibilidades de éxito. El objetivo de este trabajo es presentar un caso clínico de gastrinoma hepático primario en México, tratado de manera exitosa mediante segmentectomía hepática derecha.

Spontaneous regression of gastric gastrinoma after resection of metastases to the lesser omentum: A case report and review of literature.

BACKGROUND: Gastric gastrinoma and spontaneous tumor regression are both very rarely encountered. We report the first case of spontaneous regression of gastric gastrinoma. CASE SUMMARY: A 37-year-old man with a 9-year history of chronic abdominal pain was referred for evaluation of an 8 cm mass in the lesser omentum discovered incidentally on abdominal computed tomography. The tumor was diagnosed as grade 2 neuroendocrine neoplasm (NEN) on endoscopic ultrasound-guided fine-needle aspiration. Screening esophagogastroduodenoscopy revealed a 7 mm red polypoid lesion with central depression in the gastric antrum, also confirmed to be a grade 2 NEN. Laparoscopic removal of the abdominal mass confirmed it to be a metastatic gastrinoma lesion. The gastric lesion was subsequently diagnosed as primary gastric gastrinoma. Three months later, the gastric lesion had disappeared without treatment. The patient remains symptom-free with normal fasting serum gastrin and no recurrence of gastrinoma during 36 mo of follow-up. CONCLUSION: Gastric gastrinoma may arise as a polypoid lesion in the gastric antrum. Spontaneous regression can rarely occur after biopsy.

Imaging of Pancreatic-Neuroendocrine Tumours: An Outline of Conventional Radiological Techniques.

INTRODUCTION: Pancreatic Neuroendocrine Tumours (p-NETs) are an important disease entity and comprise of peptide-secreting tumours often with a functional syndrome. Accounting for a small percentage of all pancreatic tumours, they have a good overall survival rate when diagnosed early, with surgery being curative. The role of nuclear medicine in the diagnosis and treatment of these tumours is evident. However, the vast majority of patients will require extensive imaging in the form of conventional radiological techniques. It is important for clinicians to have a fundamental understanding of the p-NET appearances to aid prompt identification and to help direct management through neoplastic staging. METHODS: This article will review the advantages and disadvantages of conventional radiological techniques in the context of p-NETs and highlight features that these tumours exhibit. CONCLUSION: Pancreatic neuroendocrine tumours are a unique collection of neoplasms that have markedly disparate clinical features but similar imaging characteristics. Most p-NETs are small and welldefined with homogenous enhancement following contrast administration, although larger and less welldifferentiated tumours can demonstrate areas of necrosis and cystic architecture with heterogeneous enhancement characteristics. Prognosis is generally favourable for these tumours with various treatment options available. However, conventional radiological techniques will remain the foundation for the initial diagnosis and staging of these tumours, and a grasp of these modalities is extremely important for physicians.

Management of Primary Lymph Nodal Gastrinoma With Liver Metastases Resulting in Zollinger-Ellison Syndrome.

Primary lymph node gastrinoma has been defined as gastrin-producing tumor present in lymph nodes and predominantly found in well-defined anatomical region known as gastrinoma triangle. They are usually localized preoperatively with imaging, and their surgical resection results in long-term relief. The authors report a case of unresectable primary lymph nodal gastrinoma with liver metastases in a 14-year-old adolescent boy with proven histopathology detected on Ga-DOTANOC whole-body PET/CT scan followed by preoperative multiple Lu-DOTATATE cycles for cytoreduction. Subsequent surgical resection of residual mass resulted in complete response with a follow-up of around 4 years in this unusual case of Zollinger-Ellison syndrome.

Primary lymph node gastrinoma: A single institution experience.

BACKGROUND: Gastrinomas are rare neuroendocrine tumors that ectopically secrete gastrin and classically originate within the duodenum or pancreas. The presence of primary lymph node gastrinoma is controversial. We report on a single institution's experience with gastrinoma, with focus on primary lymph node tumors. METHODS: Patients who underwent operative resection of gastrinoma between 1992 and 2016 at a single institution were identified. A diagnosis of primary lymph node gastrinoma was defined as tumor confined to one or more resected peripancreatic lymph nodes, negative localization for any extra-nodal disease and normal gastrin postresection. RESULTS: In the study, 39 consecutive patients underwent operative resection of gastrinoma. Mean age was 53 years and 49% were male. 93% of patients had successful preoperative localization. Furthermore, 19 patients (49%) underwent enucleation of their tumor and 14 (35.9%) a pancreatic resection. Overall 5- and 10-year survival for all patients was 80.8% and 60.7%, respectively. Primary lymph node gastrinoma was identified in 11 cases (28.2%). The presentation of primary lymph node and non-primary lymph node patients were similar. There was no significant difference in operation type, tumor size, or overall survival. At median follow-up of 59 months, patients with primary lymph node gastrinoma were less likely to have persistent or recurrent disease (9.1% vs 42.9%, P = .04). CONCLUSION: This series supports the existence of primary lymph node gastrinomas, and indicates that as many as 1 in 4 patients with gastrinoma have this form of the disease. This entity should be considered when an isolated pathologic lymph node is identified, although thorough exploration is still recommended to exclude other occult disease.

A case of type 1 multiple endocrine neoplasia with esophageal stricture successfully treated with endoscopic balloon dilation and local steroid injection combined with surgical resection of gastrinomas.

BACKGROUND: In type 1 multiple endocrine neoplasia (MEN1), esophageal diseases association with excessive gastrin secretion in Zollinger-Ellison syndrome (ZES) sometimes develop. Here, we reported a case of MEN1/ZES, who developed dysphagia due to reflux esophagitis with severe esophageal stricture. Treatment for his esophageal stricture and ZES was discussed. CASE PRESENTATION: A 43-year-old man with progressive dysphagia and diarrhea was referred to the teaching hospital. He had a history of recurrent duodenojejunal perforations despite the anti-secretory medication. Blood examinations revealed elevated serum gastrin, calcium, and parathyroid hormone. Upper gastrointestinal endoscopy demonstrated a severe esophageal stricture, multiple gastroduodenal ulcer scars, and a duodenal submucosal tumor. Enhanced computed tomography showed multiple hypervascular tumors within the pancreas and duodenum, suggestive of MEN1. Genetic examination demonstrated a pathogenic MEN1 mutation. Repetitive endoscopic esophageal dilatation with intralesional corticosteroid injection, coupled with pancreatoduodenectomy were performed to improve the patient's symptoms and to treat pancreatic tumors. The histology of multiple tumors in the duodenum and pancreas were all consistent with neuroendocrine tumors. His hypergastrinemia subsided and he remained asymptomatic in his gastrointestinal tract after these treatments. CONCLUSION: For esophageal stenosis in case of MEN1/ZES, anti-secretory therapy and endoscopic dilatation with corticosteroid injection could be recommended. However, in refractory cases with repetitive and/or severe complications due to high acid secretion, surgical treatment could be considered as an option.

Management of pancreatic gastrinoma associated with Von Hippel-Lindau disease: a case report.

BACKGROUND: Pancreatic neuroendocrine tumors (PNET) are a heterogeneous group and constitute 1.3% of all pancreatic tumors. Approximately 10% of these occur in the context of hereditary syndromes, such as VHL disease. CASE REPORT: We report a case of a female patient of 37 years diagnosed VHL and intervened on several occasions by cerebral hemangioblastoma and renal carcinomas. During its follow-up she was diagnosed 2 gastrinomas functioning under 2 cm were enucleated. Later developed new PNET and underwent a total duodenopancreatectomy without pyloric preservation. DISCUSSION: The management of PNET in VHL is difficult due to the association of multiple tumors in different organs and the morbidity and mortality associated with the surgery of the pancreas. Management must be individualized for each patient, based on the ability to produce hormones and present symptoms, the size and location, and in the context of other tumors that usually present in these patients.

Imaging of neuroendocrine tumors of the pancreas.

Pancreatic neuroendocrine tumors (PNETs) are rare and represent a heterogeneous disease. PNET can be functioning or non-functioning with different clinical presentations and different prognosis based on WHO and pTNM classifications. The role of imaging includes the localization of small functioning tumor, differentiation of these tumors from adenocarcinoma, identification of signs of malignancy and evaluation of extent. PNETs have a broad spectrum of appearance. On CT and MRI, most of functioning PNETs are well defined small tumors with intense and homogeneous enhancement on arterial and portal phases. However, some PNETs with a more fibrous content may have a more delayed enhancement that is best depicted on the delayed phase. Other PNETs can present as purely cystic, complex cystic and solid tumors and calcified tumors. Non-functioning PNETs are larger with less intense and more heterogeneous enhancement. Functional imaging is useful for disease staging, to detect disease recurrence or the primary but also to select patient candidate for peptide receptor radiometabolic treatment. Somatostatin receptor scintigraphy (SRS) (Octreoscan®) is still the most available technique. Gallium 68-SST analogue PET have been demonstrated to be more sensitive than SRS-SPEC and it will be the future of functional imaging for NET. Finally, 18FDG PET/CT is indicated for more aggressive PNET as defined either by negative SRS and huge tumor burden or ki67 above 10% or poorly differentiated PNEC tumors.

(68)Ga-DOTATOC-PET/CT for effective diagnosis and treatment of pancreatic tail gastrinoma with multiple liver metastases: a case report.

A 40-year-old man admitted to our hospital with diarrhea underwent abdominal computed tomography (CT) which showed multiple masses in the liver and pancreatic tail. Although there were no abnormal accumulations with fluorodeoxyglucose ((18)F) positron emission tomography (FDG-PET), (68)Ga-DOTATOC-PET/CT detected obvious abnormal accumulations for the both lobes of liver and pancreatic tail tumors. The serum gastrin was markedly high, and liver tumor biopsy demonstrated the presence of malignant cells with round nuclei that were positive for gastrin and somatostatin receptor. The patient was diagnosed with pancreatic tail gastrinoma with multiple liver metastases and treated with octreotide, everolimus, and a proton pump inhibitor which functionally controlled tumor growth. This case demonstrates (68)Ga-DOTATOC-PET/CT as a useful modality for the localization, qualitative diagnosis, and treatment of gastrinoma.