Endocrine neoplasia represents an increasingly broad spectrum of disorders. Endocrine neoplasms range from incidental findings to potentially lethal malignancies. In this paper, we cover the impact ...of pathology in the interpretation of the clinic-pathological, genetic, and radiographic features underpinning these neoplasms. We highlight the critical role of multidisciplinary interactions in structuring a rational diagnostic and efficient therapeutic plan and emphasize the role of histopathological input in decision-making. In this context, standardized pathology reporting and second opinion endocrine pathology review represent relevant tools to improve the overall diagnostic workup of patients affected by endocrine tumors in every specific scenario. In fact, although a relevant proportion of cases may be correctly identified based on clinical presentation and biochemical/imaging investigations, a subset of cases presents with atypical findings that may lead to an inappropriate diagnosis and treatment plan based on a wrong pathological diagnosis if all pieces of the puzzle are not correctly considered. Pathologists have a responsibility to actively guide clinicians before and during surgical procedures to prevent unnecessary interventions. In all areas of endocrine pathology, pathologists must understand the complexity of tissue preservation and assay sensitivities and specificities to ensure the optimal quality and interpretation of diagnostic material. Finally, pathologists are central actors in tumor tissue biobanking, which is an expanding field in oncology that should be promoted while adhering to strict ethical and methodological standards.
The History of Acromegaly de Herder, Wouter W
Neuroendocrinology,
01/2016, Letnik:
103, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Pierre Marie coined the term 'acromegaly' in 1886 and linked it to a distinct clinical disease with a characteristic clinical picture. However, Pierre Marie was not the first physician to give a full ...record of the clinical picture of acromegaly; others had preceded him, like the Dutch physician Johannes Wier. After Marie, pituitary enlargement was noted in almost all patients with acromegaly. Subsequently it was discovered that pituitary hyperfunction caused by a pituitary tumour was indeed the cause of acromegaly. The cause of acromegaly could be further determined after the discovery of growth hormone (GH) and insulin-like growth factor I (IGF-I) and after demonstrating an association with GH hypersecretion and elevated circulating IGF-I. From the beginning of the 20th century, acromegaly could be treated by pituitary surgery and/or radiotherapy. After 1970, medical therapies were introduced that could control acromegaly. First, dopamine agonists were introduced, followed by somatostatin analogues and GH receptor blockers.
One century ago, in 1922, Frederick G Banting, Charles H Best, James B Collip and John J R Macleod first published their experiments resulting in the isolation of a hypoglycemic factor, named ...insulin, from a solution extract from a dog's pancreas. One year later, in 1923, a hyperglycemic factor named glucagon was isolated by Charles P Kimball and John R Murlin. In the following years, it could be demonstrated that pancreatic islet alpha- and beta-cell neoplasms and hyperplasias could inappropriately secrete excessive amounts of these two hormones. This review is a sequel to the discovery of insulin and glucagon and introduces the history of this fascinating group of neuroendocrine neoplasms and hyperplasias of the pancreas.
Context: Peptide receptor radionuclide therapy (PRRT) with Lutetium-177-DOTA.sup.0-Tyr.sup.3 octreotate (.sup.177Lu-DOTATATE) results in an increase of progression-free survival and quality of life ...in patients with progressive, well-differentiated neuroendocrine neoplasms (NENs). Objective: To study the effect of .sup.177Lu-DOTATATE in patients with carcinoid syndrome and radiologically stable or newly diagnosed disease treated solely for the purpose of symptom reduction. Design: Retrospective cohort study. Setting: Tertiary care hospital. Patients: Twenty-two patients with a metastatic midgut NEN, elevated urinary 5-hydroxyindolacetic acid excretion, and flushing and/or diarrhea despite treatment with a somatostatin analog, without documented disease progression. Intervention: PRRT with .sup.177Lu-DOTATATE (intended cumulative dose: 29.6 GBq) with a primary aim to reduce symptoms. Results: After PRRT, mean bowel movement frequency (BMF) decreased from 6.1 + or - 3.4 to 4.6 + or - 3.6 per day (P = 0.009). Flushes decreased from 4.3 + or - 2.9 to 2.4 + or - 2.7 flushes per day (P = 0.002). A decrease of BMF of more than 30% occurred in 47% of patients with baseline BMF of 4 or more (n = 17). In patients with greater than or equal to2 episodes of flushing a day (n = 15), 67% of patients had more than 50% decrease of daily flushing. A decrease in urinary 5-hydroxyindolacetic acid excretion of more than 30% was seen in 56% of patients. The European Organization for Research and Treatment of Cancer-Core Module diarrhea subscale score showed a trend toward improvement by an average of 16.7 + or - 33.3 points (P = 0.11). Conclusion: PRRT with .sup.177Lu-DOTATATE effectively reduced diarrhea and flushing in patients with carcinoid syndrome and can be considered for symptomatic treatment of carcinoid syndrome insufficiently controlled with somatostatin analogs. Key Words: neuroendocrine tumor, PRRT, carcinoid syndrome
Despite the fact that most gastroenteropancreatic neuroendocrine tumors (GEPNETs) are slow-growing, median overall survival (OS) in patients with liver metastases is 2 to 4 years. In metastatic ...disease, cytoreductive therapeutic options are limited. A relatively new therapy is peptide receptor radionuclide therapy with the radiolabeled somatostatin analog (177)Lu-DOTA(0),Tyr(3)octreotate. Here we report on the toxicity and efficacy of this treatment, performed in over 500 patients.
Patients were treated up to a cumulative dose of 750 to 800 mCi (27.8-29.6 GBq), usually in four treatment cycles, with treatment intervals of 6 to 10 weeks. Toxicity analysis was done in 504 patients, and efficacy analysis in 310 patients.
Any hematologic toxicity grade 3 or 4 occurred after 3.6% of administrations. Serious adverse events that were likely attributable to the treatment were myelodysplastic syndrome in three patients, and temporary, nonfatal, liver toxicity in two patients. Complete and partial tumor remissions occurred in 2% and 28% of 310 GEPNET patients, respectively. Minor tumor response (decrease in size > 25% and < 50%) occurred in 16%. Median time to progression was 40 months. Median OS from start of treatment was 46 months, median OS from diagnosis was 128 months. Compared with historical controls, there was a survival benefit of 40 to 72 months from diagnosis.
Treatment with (177)Lu-DOTA(0),Tyr(3)octreotate has few adverse effects. Tumor response rates and progression-free survival compare favorably to the limited number of alternative treatment modalities. Compared with historical controls, there is a benefit in OS from time of diagnosis of several years.
Long-acting depot formulations of the currently available somatostatin analogues are considered the first-line treatment for control of hormonal excess by hormone-producing neuroendocrine tumors of ...the gastrointestinal tract and pancreas. These drugs are currently also considered the first-line treatment for tumor control of both hormone-producing and non-hormone-producing neuroendocrine tumors of the gastrointestinal tract and pancreas. These drugs need coupling and interaction with specific somatostatin receptor subtypes, which are expressed on the cells of neuroendocrine tumors of the gastrointestinal tract and pancreas.
Gastroenteropancreatic neuroendocrine tumours Modlin, Irvin M, Prof; Oberg, Kjell, Prof; Chung, Daniel C, MD ...
The lancet oncology,
2008, 2008-Jan, 2008-01-00, 20080101, Letnik:
9, Številka:
1
Journal Article
Recenzirano
Summary Gastroenteropancreatic (GEP) neuroendocrine tumours (NETs) are fairly rare neoplasms that present many clinical challenges. They secrete peptides and neuroamines that cause distinct clinical ...syndromes, including carcinoid syndrome. However, many are clinically silent until late presentation with mass effects. Investigation and management should be highly individualised for a patient, taking into consideration the likely natural history of the tumour and general health of the patient. Management strategies include surgery for cure (which is achieved rarely) or for cytoreduction, radiological intervention (by chemoembolisation and radiofrequency ablation), chemotherapy, and somatostatin analogues to control symptoms that result from release of peptides and neuroamines. New biological agents and somatostatin-tagged radionuclides are under investigation. The complexity, heterogeneity, and rarity of GEP NETs have contributed to a paucity of relevant randomised trials and little or no survival increase over the past 30 years. To improve outcome from GEP NETs, a better understanding of their biology is needed, with emphasis on molecular genetics and disease modeling. More-reliable serum markers, better tumour localisation and identification of small lesions, and histological grading systems and classifications with prognostic application are needed. Comparison between treatments is currently very difficult. Progress is unlikely to occur without development of centers of excellence, with dedicated combined clinical teams to coordinate multicentre studies, maintain clinical and tissue databases, and refine molecularly targeted therapeutics.
Small-intestinal neuroendocrine tumors (SI-NETs) have a modest but significantly higher prevalence and worse prognosis in male patients.
This work aims to increase understanding of this sexual ...dimorphism in SI-NETs.
Retrospectively, SI-NET patients treated in a single tertiary center were included and analyzed for disease characteristics. Estrogen receptor 1 (ESR1) and 2 (ESR2), progesterone receptor (PGR), and androgen receptor (AR) messenger RNA (mRNA) expression was assessed in primary tumors and healthy intestine. Estrogen receptor alpha (ERα) and AR protein expression were analyzed by immunohistochemistry in primary tumors and mesenteric metastases.
Of the 559 patients, 47% were female. Mesenteric metastasis/fibrosis was more prevalent in men (71% / 46%) than women (58% / 37%; P = 0.001 and P = 0.027, respectively). In women, prevalence of mesenteric metastases increased gradually with age from 41.1% in women <50 years to 71.7% in women >70 years. Increased expression of ESR1 and AR mRNA was observed in primary tumors compared to healthy intestine (both P < 0.001). ERα staining was observed in tumor cells and stroma with a strong correlation between tumor cells of primary tumors and mesenteric metastases (rho = 0.831, P = 0.02), but not in stroma (rho = -0.037, P = 0.91). AR expression was only found in stroma.
Sexual dimorphism in SI-NETs was most pronounced in mesenteric disease, and the risk of mesenteric metastasis in women increased around menopause. The combination of increased ERα and AR expression in the SI-NET microenvironment suggests a modulating role of sex steroids in the development of the characteristic SI-NET mesenteric metastasis and associated fibrosis.
PDF
