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Gland Surgery Feb 2018Pancreatic neuroendocrine tumors (pNETs) constitute a heterogenous group of malignancies with varying clinical presentation, tumor biology and prognosis. The incidence... (Review)
Review
Pancreatic neuroendocrine tumors (pNETs) constitute a heterogenous group of malignancies with varying clinical presentation, tumor biology and prognosis. The incidence of pNETs has steadily increased during the last decades with an estimated incidence 2012 of 4.8/100,000. Recent whole genome sequencing of pNETs has demonstrated mutations in the DNA repair genes MUTYH and point mutations and gene fusions in four main pathways from chromatin remodeling, DNA damage repair, activation of mechanistic target of rapamycin (mTOR) signaling and the telomere maintenance. This new information will be the foundation for new therapies in the near future for malignant pNETs. The functioning pNETs constitute about 30-40% of all pNETs displaying nine different clinical syndromes: insulinoma, Zollinger-Ellison, Verner-Morrison, glucagonoma, somatostatinomas, ectopic adrenocorticotropic hormone (ACTH) and parathyroid hormone related peptide (PTH-rP) syndromes. Single patients might also present carcinoid syndrome. The diagnostic work-up include histopathology with the new WHO 2017 Classification, biomarkers (CgA, NSE), radiology and molecular imaging including CT-scan, magnetic resonance imaging (MRI), ultrasound and PET-scan. A cornerstone in the treatment of pNETs is surgery which is rarely curative but can reduce the clinical symptoms by debulking which also include radiofrequency ablation, embolization of liver metastases. Medical treatment includes chemotherapy and the targeted agents such as everolimus, sunitinib and peptide receptor radiotherapy (PRRT). Somatostatin analogs has for the last decades been the main stay for management for clinical symptoms related to functioning pNETs and is often combined with new targeted agents as well as chemotherapy. Long-term management of functioning pNETs need a combination of different procedures, surgery, local ablation, targeted agents and somatostatin analogs. Future therapies might be based on the recent advances in molecular genetics and tumor biology.
PubMed: 29629316
DOI: 10.21037/gs.2017.10.08 -
Gland Surgery Feb 2018Pancreatic neuroendocrine tumours (PNETs) are rare. They are generally accepted to be slow-growing and have an indolent course. These tumours can be non-functioning or... (Review)
Review
Pancreatic neuroendocrine tumours (PNETs) are rare. They are generally accepted to be slow-growing and have an indolent course. These tumours can be non-functioning or functioning, consisting of a biochemically heterogeneous group of tumours including insulinomas, gastrinomas, carcinoids and glucagonomas. Although surgery remains the mainstay of treatment, controversy still exists especially for non-functioning tumours <2 cm in size. Whether these should be resected or undergo intensive surveillance remains unclear. The surgical approach depends on local expertise. Many studies have shown comparable short-term surgical outcome with laparoscopic pancreatic resection compared to open techniques, however data on long-term oncological outcome are still lacking. On the other hand, liver metastasis occurs in as high as 80% of PNET patients. Five-year survival rate is only 30% if left untreated compared to 60-80% if complete resection is achieved. Current evidence supports liver resection with an aim for symptomatic control and to improve survival in those with respectable disease and no extra-hepatic metastasis. Palliative debunking can be considered in those with intractable symptoms. This article reviews the current evidence on pancreatic resection for PNETs, in particular the role of laparoscopic resection and the management of liver metastasis.
PubMed: 29629318
DOI: 10.21037/gs.2017.12.05 -
Biomarkers in Medicine Nov 2016The proglucagon-derived peptide hormone, glucagon, comprises 29 amino acids. Its secretion from the pancreatic α cells is regulated by several factors. Glucagon... (Review)
Review
The proglucagon-derived peptide hormone, glucagon, comprises 29 amino acids. Its secretion from the pancreatic α cells is regulated by several factors. Glucagon increases blood glucose levels through gluconeogenesis and glycogenolysis. Elevated plasma concentrations of glucagon, hyperglucagonemia, may contribute to diabetes. However, hyperglucagonemia is also observed in other clinical conditions than diabetes, including nonalcoholic fatty liver disease, glucagon-producing tumors and after gastric bypass surgery. Here, we review the current literature on hyperglucagonemia in disease with a particular focus on diabetes, and finally speculate that the primary physiological importance of glucagon may not reside in glucose homeostasis but in regulation of amino acid metabolism exerted via a hitherto unrecognized hepato-pancreatic feedback loop.
Topics: Diabetes Mellitus; Glucagon; Glucagon-Like Peptide 1; Glucagonoma; Humans; Liver; Neoplasms; Non-alcoholic Fatty Liver Disease; Oxyntomodulin; Pancreas; Receptors, Glucagon
PubMed: 27611762
DOI: 10.2217/bmm-2016-0090 -
Biomedica : Revista Del Instituto... Jun 2016Necrolytic migratory erythema is a rare paraneoplastic dermatosis that may be the first clinical manifestation of the glucagonoma syndrome, a disorder characterized by...
Necrolytic migratory erythema is a rare paraneoplastic dermatosis that may be the first clinical manifestation of the glucagonoma syndrome, a disorder characterized by mucocutaneous rash, glucose intolerance, hypoaminoacidemia, hyperglucagonaemia and pancreatic glucagonoma. The clinical case of a 45-year-old woman is presented. She had been experiencing weight loss, polydipsia, polyphagia, postprandial emesis, excessive hair loss and abdominal pain for two months. Erythematous, scaly and migratory plaques with 20 days of evolution were found on her trunk, perineum, elbows, hands, feet, inframammary and antecubital folds. The skin biopsy revealed noticeable vacuolar changes in high epidermal cells, extensive necrosis and thin orthokeratotic cornified layer. These findings pointed to a diagnosis of necrolytic migratory erythema. A suggestion was made to investigate a pancreatic glucagonoma. Laboratory tests showed moderate anemia, hyperglycemia and marked hyperglucagonaemia. Abdominal ultrasound revealed a mass in the tail of the pancreas measuring 6 x 5 x 5 cm which was resected. The histopathological findings were compatible with a diagnosis of glucagonoma, as confirmed by immunohistochemistry. Skin symptoms disappeared 10 days after the tumor resection. We can conclude that the histological changes defined may be clues that can lead the search for a distant skin disease and allow for its diagnosis. The histological pattern of vacuolation and epidermal necrosis should arouse suspicion of pancreatic glucagonoma.
Topics: Biopsy; Female; Glucagonoma; Humans; Hyperglycemia; Necrolytic Migratory Erythema; Necrosis; Pancreatic Neoplasms; Skin
PubMed: 27622478
DOI: 10.7705/biomedica.v36i3.2723 -
Annals of Medicine and Surgery (2012) May 2022Glucagonoma is a rare neuroendocrine tumor (NET). Most glucagonomas are in the tail or body of the pancreas and are diagnosed at a metastatic stage. We report a case of...
INTRODUCTION AND IMPORTANCE
Glucagonoma is a rare neuroendocrine tumor (NET). Most glucagonomas are in the tail or body of the pancreas and are diagnosed at a metastatic stage. We report a case of an early recurrence after surgical resection of a glucagonoma and its management.
CASE REPORT
We present a case of a 44-year-old female patient with no medical and surgical history, operated on in May 2018 for pancreatic glucagonoma revealed by skin necrolytic migratory erythema. The patient was regularly monitored by clinical exams and CT scans. In December 2020 (31 months postoperatively), we noticed the recurrence of the cutaneous lesions.Admission laboratory measurements demonstrated hyperglycemia as well as elevated blood Glucagon levels. Explorations showed 3 retro-pancreatic lesions. Based on these findings, we concluded that it was a recurrence of her glucagonoma. The patient was operated on by median laparotomy We performed a warshow's procedure.Pathology confirmed the endocrine nature of the 3 nodules. We are currently 6 months behind the surgery. The examination is strictly normal with no recurrence of the skin lesions so far.
CLINICAL DISCUSSION
Surgical resection on a recurrent glucagonoma is what is unique in our case as we haven't found any case in the literature to our knowledge.What is also unique about our case is both the local aspect of the recurrence and the multiplicity of the tumors observed as multiple nodules around the tail of the pancreas. These lesions were not metastatic lymph nodes as confirmed by pathology. Probably it was an effraction of the big tumor at enucleation.
CONCLUSION
Due to its rareness, there is no clear consensus on the management of glucagonomas therefore we chose to write our case in order to further enrich the literature to achieve one-day guidelines for glucagonomas treatment.
PubMed: 35638031
DOI: 10.1016/j.amsu.2022.103604 -
Tomography (Ann Arbor, Mich.) Jan 2023Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) comprise a heterogeneous group of neoplasms, which derive from cells of the diffuse neuroendocrine system that... (Review)
Review
Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) comprise a heterogeneous group of neoplasms, which derive from cells of the diffuse neuroendocrine system that specializes in producing hormones and neuropeptides and arise in most cases sporadically and, to a lesser extent, in the context of complex genetic syndromes. Furthermore, they are primarily nonfunctioning, while, in the case of insulinomas, gastrinomas, glucagonomas, vipomas, and somatostatinomas, they produce hormones responsible for clinical syndromes. The GEP-NEN tumor grade and cell differentiation may result in different clinical behaviors and prognoses, with grade one (G1) and grade two (G2) neuroendocrine tumors showing a more favorable outcome than grade three (G3) NET and neuroendocrine carcinoma. Two critical issues should be considered in the NEN diagnostic workup: first, the need to identify the presence of the tumor, and, second, to define the primary site and evaluate regional and distant metastases. Indeed, the primary site, stage, grade, and function are prognostic factors that the radiologist should evaluate to guide prognosis and management. The correct diagnostic management of the patient includes a combination of morphological and functional evaluations. Concerning morphological evaluations, according to the consensus guidelines of the European Neuroendocrine Tumor Society (ENETS), computed tomography (CT) with a contrast medium is recommended. Contrast-enhanced magnetic resonance imaging (MRI), including diffusion-weighted imaging (DWI), is usually indicated for use to evaluate the liver, pancreas, brain, and bones. Ultrasonography (US) is often helpful in the initial diagnosis of liver metastases, and contrast-enhanced ultrasound (CEUS) can solve problems in characterizing the liver, as this tool can guide the biopsy of liver lesions. In addition, intraoperative ultrasound is an effective tool during surgical procedures. Positron emission tomography (PET-CT) with FDG for nonfunctioning lesions and somatostatin analogs for functional lesions are very useful for identifying and evaluating metabolic receptors. The detection of heterogeneity in somatostatin receptor (SSTR) expression is also crucial for treatment decision making. In this narrative review, we have described the role of morphological and functional imaging tools in the assessment of GEP-NENs according to current major guidelines.
Topics: Humans; Positron Emission Tomography Computed Tomography; Syndrome; Neuroendocrine Tumors; Prognosis; Radiologists
PubMed: 36828370
DOI: 10.3390/tomography9010018 -
Journal of the Royal College of... Apr 1988Our knowledge of the mechanisms involved in the regulation of somatotroph cell growth is scanty and much work is still needed to elucidate the role of different growth... (Review)
Review
Our knowledge of the mechanisms involved in the regulation of somatotroph cell growth is scanty and much work is still needed to elucidate the role of different growth factors and the mechanisms involved in oncogene activation in both normal and tumour cell growth. However, there are several recent, important clinical ramifications from our improved understanding of GH neuroregulation. The use of long-acting SS analogues is valuable in the treatment of acromegaly, probably in acute variceal haemorrhage and it also produces symptomatic improvement in patients with vipomas and glucagonomas. GHRH may be of value in the treatment of short stature due to hypothalamic GHRH deficiency but further definitive studies are now required to provide convincing evidence that this line of treatment is of greater benefit than the use of synthetic recombinant human GH. Inhibition of GH release may be of value in prevention of both acute and chronic complications of insulin-dependent diabetes mellitus. The use of cholinergic muscarinic receptor blockade in this context may be particularly useful because of a probably sparing of the counter-regulatory GH response to hypoglycaemia. In view of the relative ease with which nocturnal GH secretion can be abolished, we think it reasonable to consider the possible existence of a permissive or mediating role of GH in other disease states, either directly or by maintaining production of either local tissue or circulating growth factors or both.
Topics: Acromegaly; Body Constitution; Diabetes Mellitus, Type 1; Growth Hormone; Growth Hormone-Releasing Hormone; Humans; Pituitary Hormones, Anterior; Somatostatin
PubMed: 2899643
DOI: No ID Found -
Oncology Letters Aug 2015Necrolytic migratory erythema (NME), diabetes mellitus and glucagon-secreting tumors form the hallmarks of glucagonoma syndrome, and represent the major clinical...
Necrolytic migratory erythema (NME), diabetes mellitus and glucagon-secreting tumors form the hallmarks of glucagonoma syndrome, and represent the major clinical manifestations of glucagonoma. NME is usually presented as the initial complaint of patients. Due to the rare incidence of glucagonoma, its diagnosis is often delayed, which leads to its progression. Here, we report a case of NME with a typical skin rash, which was misdiagnosed and treated with corticosteroids for two years. Removal of the tumor in the pancreatic body led to the rapid relief of the symptoms. The aim of the present study is to demonstrate the typical characteristics of glucagonoma syndrome to clinicians in order to improve its diagnosis and treatment.
PubMed: 26622635
DOI: 10.3892/ol.2015.3275 -
Scientific Reports Jul 2021Specifying the exact localization of insulinoma remains challenging due to the lack of insulinoma-specific imaging methods. Recently, glucagon-like peptide-1 receptor...
Specifying the exact localization of insulinoma remains challenging due to the lack of insulinoma-specific imaging methods. Recently, glucagon-like peptide-1 receptor (GLP-1R)-targeted imaging, especially positron emission tomography (PET), has emerged. Although various radiolabeled GLP-1R agonist exendin-4-based probes with chemical modifications for PET imaging have been investigated, an optimal candidate probe and its scanning protocol remain a necessity. Thus, we investigated the utility of a novel exendin-4-based probe conjugated with polyethylene glycol (PEG) for [F]FB(ePEG12)12-exendin-4 PET imaging for insulinoma detection. We utilized [F]FB(ePEG12)12-exendin-4 PET/CT to visualize mouse tumor models, which were generated using rat insulinoma cell xenografts. The probe demonstrated high uptake value on the tumor as 37.1 ± 0.4%ID/g, with rapid kidney clearance. Additionally, we used Pdx1-Cre;Trp53;Rb mice, which developed endogenous insulinoma and glucagonoma, since they enabled differential imaging evaluation of our probe in functional pancreatic neuroendocrine neoplasms. In this model, our [F]FB(ePEG12)12-exendin-4 PET/CT yielded favorable sensitivity and specificity for insulinoma detection. Sensitivity: 30-min post-injection 66.7%, 60-min post-injection 83.3%, combined 100% and specificity: 30-min post-injection 100%, 60-min post-injection 100%, combined 100%, which was corroborated by the results of in vitro time-based analysis of internalized probe accumulation. Accordingly, [F]FB(ePEG12)12-exendin-4 is a promising PET imaging probe for visualizing insulinoma.
Topics: Animals; Cell Line, Tumor; Disease Models, Animal; Fluorine Radioisotopes; Insulinoma; Male; Mice; Mice, Transgenic; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Radiopharmaceuticals; Rats; Xenograft Model Antitumor Assays
PubMed: 34294854
DOI: 10.1038/s41598-021-94595-6