Somatostatin receptor PET beyond the neuroendocrine tumors of the gastrointestinal tract - the review of literature.

BACKGROUND: PET of the somatostatine receptors (SSR) is a well-established functional imaging modality in the dia-gnosis of the neuroendocrine tumours (NET) of the gastro-entero-pancreatic origin (GEP). However, it can have a major impact also in other clinical entities. PURPOSE: To present a literature review focusing on the effectivity of SSR PET in the dia-gnosis beyond GEP NET. CONCLUSION: SSR PET provides an accurate dia-gnosis of pulmonary NET, pheochromocytoma and paraganglioma, it may have an important impact on their treatment and clinical management. It allows a detailed estimation of the extent of meningeoma, contributes to precise target volumes for radiotherapy delineation and is sensitive in its residuum or recurrence detection. It can be a valuable method in the syndromes of multiple endocrine neoplasia and in the localization of the source of the ectopic Cushing syndrome. It can be used in the medullary thyroid cancer. An important role of SSR PET lies in the planning and monitoring of the peptide-receptor radionuclide therapy embraced in the theranostic concept.

Multimodality Imaging Review of Multiple Endocrine Neoplasia.

OBJECTIVE. The purpose of this article is to review the clinical manifestations, endocrine tumors types, and multimodality diagnostic tools available to physicians involved in the management of patients with multiple endocrine neoplasia (MEN) syndrome, in addition to discussing relevant imaging findings and appropriate imaging follow-up. CONCLUSION. Thorough knowledge of the spectrum of tumors associated with MEN gene mutations aids in the screening, diagnostic workup, and posttreatment monitoring of patients with MEN-related gene mutations.

Multiple Endocrine Neoplasia: Spectrum of Abdominal Manifestations.

OBJECTIVE. Multiple endocrine neoplasia (MEN) syndromes are autosomal-dominant genetic disorders that predispose two or more organs of the endocrine system to tumor development. Although the diagnosis relies on clinical and serologic findings, imaging provides critical information for surgical management with the ultimate goal of complete tumor resection. CONCLUSION. This article reviews abdominal neoplasms associated with the various subtypes of MEN syndromes, with a focus on clinical presentation and characteristic imaging features.

Atypical ovarian carcinoid tumor with widespread skeletal metastases: a case report of multiple endocrine neoplasia type 1 in a young woman.

BACKGROUND: Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominant inherited condition affecting multiple endocrine organs, resulting in significant morbidity and decreased life expectancy. Early tumor identification allows for timely patient management, reduces morbidity, and improves disease outcomes. Patients with MEN1 typically present with primary hyperparathyroidism caused by multiple parathyroid tumors, however, thymic and bronchial carcinoid tumors are also less common manifestations. MEN1-related neuroendocrine tumors often show hematogenous metastasis, with the liver being the most common metastatic site. Skeletal metastases from neuroendocrine tumors are extremely rare. As few as 50 case reports were identified in a recently published literature review on skeletal metastases from carcinoid tumors. To our knowledge, studies related to MEN1 have not been previously conducted. CASE PRESENTATION: We present a case of MEN1-related atypical ovarian carcinoid presenting as the first disease manifestation in a 30-year old woman. After two years, another atypical carcinoid was incidentally diagnosed in the contralateral ovary during a caesarean section. Syndromic MEN1 was not diagnosed clinically despite her young age and bilateral involvement. The patient remained disease-free for two years without further adjuvant treatment prior to clinic presentation with complaints of chest discomfort and body pain. Radiologic and pathologic investigations identified multifocal simultaneous neuroendocrine tumors involving the parathyroid, thymus, pancreas, and adrenal glands, in addition to multiple other metastatic sites. The findings ultimately resulted in the patient being diagnosed with MEN1. CONCLUSIONS: This extremely rare case emphasizes that ovarian carcinoids, especially when bilateral, could be the initial manifestation of MEN1. The significance of this differential diagnosis was highlighted by the subsequent detection of widespread skeletal metastasis resulting from the carcinoid tumors. A low threshold of suspicion, systemic diagnostic work-up, and regular follow-up are of utmost importance to timely diagnosis of MEN1.

Síndromes de neoplasia endocrina múltiple: revisión radiológica / Multiple Endocrine Neoplasia Syndromes: Radiological Review

Los síndromes de neoplasia endocrina múltiple (MEN), incluyen una serie de enfermedades con alteraciones genéticas que se caracterizan por la presencia de tumores que afectan a dos o más glándulas endocrinas. Son síndromes con una herencia autosómica dominante e incluyen tres patrones: MEN 1 (síndrome de Wermer), MEN 2 (que incluye MEN 2A o síndrome de Sipple y MEN 2B o síndrome de Wagenmann-Froboese) y MEN 4. Los adenomas paratiroideos y el carcinoma medular tiroideo, son los tumores más frecuentes del MEN tipo 1 y 2 respectivamente. Esos síndromes son más comunes en pacientes jóvenes, con patología de afectación bilateral, múltiple o multifocal y, sobre todo, en pacientes con antecedentes familiares. Es necesario el trabajo en equipo de endocrinólogos, cirujanos, oncólogos y radiólogos para optimizar el tratamiento de esos pacientes.

Multiple endocrine neoplasia (MEN) encompasses a serial of familial genetically disorders in wich tumors simultaneusly occur in two or more endocrine organs. MEN síndromes are autosomal-dominant disorders categorized into three main patterns: MEN 1 (Wermer syndrome), MEN 2 (includes MEN 2A o Sipple syndrome and MEN 2B o Wagenmann-Froboese syndrome) and MEN 4. Parathyroid adenomas and medullary thyroid carcinoma are the most frecuent tumors in MEN 1 and MEN 2 respectively. These entities will be suspected in younger patients, bilateral, multiple or multifocal disease and, specially, in patients with family background. Cooperation between endocrinologist, surgeons, oncologists and radiologists is pivotal for optimizing patient treatment.

Role of positron emission tomography imaging in Multiple Endocrine Neoplasia syndromes.

The aim of this review was to summarize the recent developments on the role of positron emission tomography (PET) imaging using different radiopharmaceuticals in patients with multiple endocrine neoplasia (MEN) syndromes. Although most guidelines do not mention the use of PET imaging in patients with MEN syndromes, recent data seem to suggest a relevant diagnostic role of PET imaging in this setting. In particular, latest evidence has shown that somatostatin receptor PET provides a diagnostic accuracy in detecting MEN syndromes-related neuroendocrine tumours (NETs) higher than that of somatostatin receptor scintigraphy, thus influencing patient management in a significant percentage of cases. 18 F-DOPA PET seems to have a potential role in detecting MEN-2-related NETs, whereas 18 F-FDG PET is potentially useful in identifying aggressive NETs with poorer outcomes. More studies are needed to better define the role of different radiotracer-based PET imaging in patients with MEN syndromes.

Association between neuroendocrine tumors biomarkers and primary tumor site and disease type based on total 68Ga-DOTATATE-Avid tumor volume measurements.

OBJECTIVE: To determine the association between neuroendocrine tumor (NET) biomarker levels and the extent of disease as assessed by 68Ga DOTATATE PET/CT imaging. DESIGN: A retrospective analysis of a prospective database of patients with NETs. METHODS: Fasting plasma chromogranin A (CgA), neuron-specific enolase (NSE), gastrin, glucagon, vasoactive intestinal peptide (VIP) and pancreatic polypeptide (PP), and 24-h urinary 5-hydroxyindoleacetic acid (5-HIAA) levels were measured. Correlation between biomarkers and total 68Ga-DOTATATE-avid tumor volume (TV) was analyzed. RESULTS: The analysis included 232 patients. In patients with pancreatic NETs (n = 112), 68Ga-DOTATATE TV correlated with CgA (r = 0.6, P = 0.001, Spearman). In patients with multiple endocrine neoplasia type 1 (n = 39), 68Ga-DOTATATE TV correlated with glucagon (r = 0.5, P = 0.01) and PP levels (r = 0.5, P = 0.049). In patients with von Hippel-Lindau (n = 24), plasma VIP (r = 0.5, P = 0.02) and PP levels (r = 0.7, P < 0.001) correlated with 68Ga-DOTATATE TV. In patients with small intestine NET (SINET, n = 74), 68Ga-DOTATATE TV correlated with CgA (r = 0.5, P = 0.02) and 5-HIAA levels (r = 0.7, P < 0.001), with 5-HIAA ≥8.1 mg/24 h associated with metastatic disease with high positive (81.8%) and negative (85.7%) predictive values (P = 0.001). 68Ga-DOTATATE TV in patients with NET of unknown primary (n = 16) and those with NET of other primary location (n = 30) correlated with 5-HIAA levels (r = 0.8, P = 0.002 and r = 0.7, P = 0.02 respectively). CONCLUSIONS: Our data supports the use of specific NET biomarkers based on the site of the primary NET and the presence of hereditary syndrome-associated NET. High urinary 5-HIAA levels indicate the presence of metastatic disease in patients with SINET.

Multiple Endocrine Neoplasia Syndromes: A Comprehensive Imaging Review.

MEN1, MEN2, and MEN4 comprise a series of familial disorders involving the simultaneous occurrence of tumors in more than one endocrine organ, collectively known as multiple endocrine neoplasia. Patients with this family of disorders develop tumors of the parathyroid gland, pancreas, pituitary gland, adrenal gland, and thyroid gland, along with miscellaneous neuroendocrine tumors of the respiratory and gastrointestinal tracts. Although some patients undergo early prophylactic surgical management, particularly in the setting of familial medullary thyroid carcinoma, many develop tumors later in life. These tumors are often discovered at imaging for screening purposes. Recognition of the imaging features of the known tumors is important for appropriate patient management.

Accuracy of 68Ga DOTANOC PET/CT Imaging in Patients With Multiple Endocrine Neoplasia Syndromes.

OBJECTIVE: The aim of this study was to evaluate the role of 68Ga DOTANOC PET/CT imaging in patients with multiple endocrine neoplasia (MEN) syndromes. PATIENTS AND METHODS: Data of 33 patients (age, 33.5 [13.8] years; male 14/female 19) with MEN syndromes (MEN 1, 9; MEN 2A, 19; MEN 2B, 5) who underwent 41 68Ga DOTANOC PET/CT studies were retrospectively analyzed. Twenty PET/CTs were done for staging and 21 for restating. PET/CT images were evaluated in consensus by 2 nuclear medicine physicians, qualitatively and semiquantitatively (SUV(max)). A combination of histopathology, clinical, and biomarker follow-up was taken as reference standard. RESULTS: Of the total 41 68Ga DOTANOC PET/CTs, 34 were interpreted as positive for neuroendocrine tumors (NETs) and 7 as negative. The patientwise sensitivity of PET/CT was 94% (95% confidence interval [CI], 80-99), specificity was 71% (95% CI, 29-96), positive predictive value was 94% (95% CI, 80-99), negative predictive value was 71% (95% CI, 29-96), and accuracy was 90%. A total of 74 disease sites were demonstrated on PET/CT, including 41 primary NETs (pancreas, 10; stomach, 2; pheochromocytoma, 10; medullary thyroid carcinoma, 19), 31 metastatic sites (lymph node, 15; liver, 10; bone, 4; lung, 1; breast, 1), and 2 parathyroid adenomas. Lesionwise sensitivity, positive predictive value, and accuracy of PET/CT were 93%, 96%, and 90% overall, 89%, 95%, and 85% for primary tumors, and 100%, 97%, and 97% for metastasis, respectively. Among primary tumors, the SUV(max) of medullary thyroid carcinoma was significantly lower than gastro pancreatic NETs (P = 0.003) and pheochromocytomas (P = 0.003). No site-specific difference was seen in SUV(max) of metastatic lesions. CONCLUSIONS: 68Ga DOTANOC PET/CT shows high diagnostic accuracy in MEN syndrome and can demonstrate both primary and metastatic NETs in these patients.

Impact of Ga-68 DOTATOC PET/CT on the diagnosis and treatment of patients with multiple endocrine neoplasia.

PURPOSE: To evaluate the impact of Ga-68 DOTATOC PET/CT on diagnosis and therapeutic management of patients with multiple endocrine neoplasia (MEN). MATERIALS AND METHODS: We did 28 Ga-68 DOTATOC PET/CT in 21 MEN patients (10 female, 11 men; mean age 41.3 years). 109 lesions detected were classified into MEN-associated lesions [i.e., neuroendocrine tumors (NET)] and non-MEN-associated lesions for PET, CT, and PET/CT. The impact of Ga-68 DOTATOC PET/CT on diagnosis and therapeutic management of patients with MEN were assessed by the records of the interdisciplinary NET tumor board including histopathological findings, clinical and radiological follow-up. RESULTS: Ga-68 DOTATOC PET/CT had an impact on diagnosis and therapeutic management in 10/21 (47.6%) MEN patients. For detecting NET lesions in MEN patients Ga-68 DOTATOC PET/CT reached a sensitivity/specificity of 91.7%/93.5%. There was a significant difference for the detection rate between Ga-68 DOTATOC PET/CT and CT alone (p < 0.001) both using contrast-agent (p = 0.002) or not (p < 0.001) and also a significant difference between contrast-enhanced (CE-) CT and non-CE-CT alone (p = 0.006). CONCLUSIONS: GA-68 DOTATOC PET/CT allows a high detection rate of NET lesions in the context of MEN-1 syndrome as well as influence therapeutic management in nearly up to half of the patients. GA-68 DOTATOC PET/CT should include a CE-CT to improve MEN-associated NET lesion detection.

Multiple endocrine neoplasia with pulmonary localization: a new protocol of approach.

We present three patients with bronchial carcinoids, in which a more probed study emphasized the presence of three multiple endocrine neoplasia (MEN). Assessment included a total-body computerized tomography, a total-body single-photon emission computerized tomography by 111In-DTPA-D-Phe1 octreotide, and genetic map. Two patients presented an atypical MEN 1 and one patient showed an atypical MEN 1 with a familial medullary thyroid carcinoma. All patients were operated upon: two are still alive and one died 50 months after the first intervention. Precocious diagnosis of MEN permits a good long-term outcome.

Accuracy of [18F]fluorodopa positron emission tomography for diagnosing and localizing focal congenital hyperinsulinism.

OBJECTIVES: Focal lesions in infants with congenital hyperinsulinism (HI) represent areas of adenomatosis that express a paternally derived ATP-sensitive potassium channel mutation due to embryonic loss of heterozygosity for the maternal 11p region. This study evaluated the accuracy of 18F-fluoro-l-dihydroxyphenylalanine ([18F]DOPA) positron emission tomography (PET) scans in diagnosing focal vs. diffuse disease and identifying the location of focal lesions. DESIGN: A total of 50 infants with HI unresponsive to medical therapy were studied. Patients were injected iv with [18F]DOPA, and PET scans were obtained for 50-60 min. Images were coregistered with abdominal computed tomography scans. PET scan interpretations were compared with histological diagnoses. RESULTS: The diagnosis of focal or diffuse HI was correct in 44 of the 50 cases (88%). [18F]DOPA PET identified focal areas of high uptake of radiopharmaceutical in 18 of 24 patients with focal disease. The locations of these lesions matched the areas of increased [18F]DOPA uptake on the PET scans in all of the cases. PET scan correctly located five lesions that could not be visualized at surgery. The positive predictive value of [18F]DOPA in diagnosing focal adenomatosis was 100%, and the negative predictive value was 81%. CONCLUSIONS: [18F]DOPA PET scans correctly diagnosed 75% of focal cases and were 100% accurate in identifying the location of the lesion. These results suggest that [18F]DOPA PET imaging provides a useful guide to surgical resection of focal adenomatosis and should be considered as a guide to surgery in all infants with congenital HI who have medically uncontrollable disease.

[Diagnostics and treatment of neuroendocrine tumors of the digestive tract in the light of the present standards]. / Diagnostyka i leczenie guzów neuroendokrynnych przewodu pokarmowego w swietle aktualnie obowiazujacych standardów.

Neuroendocrine tumors (NET) constitute 0.5% of all cancers appearing at the man and 2% of all tumors of the digestive tract. They constitute 70% of all NET i.e., of tumors coming from endocrine cells dispersed in the entire body of the man, creating diffuse endocrine system (DES). It is estimated that the incidence of gastroenteropatic neuroendocrine tumors (GEP) is about 3 cases/year/100000 inhabitants. The characteristic feature of these tumors is that they have the ability to produce, store and secrete peptic hormones and biogenic amines. These substances are evoking characteristic symptoms which let suspect the development of certain diseases by their influence on the human organism. Little percentage of tumors coming from cells of the endocrine system does not secrete characteristic substances - these are so-called tumors hormonaly non active. The purpose of the work is to pay attention to the diagnostic-therapeutic possibility associated with the progress of medical sciences which let more frequent recognizing and more effective treatment hence the improvement of prognosis of a sick patient with GEP. In the work, I will introduce characteristics of individual GEP tumors associated with peculiar signs and diagnostic and therapeutic possibilities. In the case of neuroendocrine tumor suspection the determination made of unique and nonunique markers NET should be directed. The attempt to localise changes is based on scintigraphy with using somatostatin analogues, endoscopic ultrasonography, the computer tomography, the magnetic resonance and positron emission tomography The histopathological examination carried out on the base of guidelines of the World Health Organization from 2000 which assembly anatomical, clinical- pathological and functional features of the tumor which let making conclusive diagnosis. In the case of the GEP diagnosis, the procedure by choice is surgical treatment which, however, as a result of its high level of advancement, is often nonradical and must be completed with pharmacological treatment. As a completing treatment, analogues of somatostatin, "interferon alpha", chemotherapy and radioisotope treatment based on marked analogues of the somatostatin receptor are used. The analysis of the documentationon GEP NET tumors permits to notice that the advanced knowledge of clinical symptoms accompanying certain tumors appropriate analysis of the laboratory tests, accurate using imaging diagnostics and the cooperation with a good patomorfological centre can increase our effectiveness in recognizing and curing GEP NET tumors and, what is more, it could increase survival and improve our patients' standard of living. What is even more essential is that the majority of them is reporting to us in the moment of the appearance of complications such as the obstruction of the digestive tract, the obstructive jaundice, nonunique pain complaints of the abdominal cavity. GEP NET tumors are another group of diseases requiring the interdisciplinary approach of many specialists to a patient-gastroenterologists, endocrinologists, radiologists, surgeons, specialists of nuclear medicine and chemotherapy

What is the link between nonlocalizing sestamibi scans, multigland disease, and persistent hypercalcemia? A study of 401 consecutive patients undergoing parathyroidectomy.

BACKGROUND: We hypothesized that nonlocalizing sestamibi scans would correlate with multigland disease and persistent primary hyperparathyroidism. METHODS: We reviewed records for 401 consecutive patients who underwent parathyroidectomy from 1999 to 2004. Gender, age, preoperative imaging, surgical findings, gland weight and volume, and 6-month calcium levels (Ca) were examined. RESULTS: We identified 289 women and 112 men, 297 of whom had a preoperative sestamibi scan localized to a single gland (localized group; LG). Ninety-six percent of the LG were found to have single-gland disease, and 4% had multigland disease (MGD). In the nonlocalized group (NLG), 76% had single-gland disease and 24% MGD. Mean gland weight was greater in the LG than in the NLG (1128 mg vs 699 mg; P < .05). Mean gland volume was larger in the LG (1.34 cc vs 0.89 cc; P < .05). A localizing sestamibi scan had a positive predictive value (PPV) of 96% and a likelihood ratio of 2.29 for predicting "curative" intraoperative parathyroid hormone drop after removal of a single abnormal gland. Patients were stratified into normocalcemic (NCa) and hypercalcemic (HCa) groups based on 6-month postoperative serum calcium data (n = 328). HCa incidence at 6 months did not differ significantly between the LG (5%) and NLG (3%). A localizing scan had a PPV of 95% for normocalcemia at 6 months. A nonlocalizing scan had a PPV of 21% for HCa at 6 months. CONCLUSIONS: Nonlocalizing sestamibi scans were more common in primary hyperparathyroidism with MGD and were associated with smaller-volume abnormal glands found at operation. Preoperative sestamibi scan-results did not predict HCa at 6 months.

Toxicity of high-activity 111In-Octreotide therapy in patients with disseminated neuroendocrine tumours.

Disseminated neuroendocrine tumours are difficult to treat and are generally not responsive to radiotherapy or chemotherapy. Nuclear medicine techniques using a radiolabelled somatostatin analogue, 111In-Octreotide, have been used for the diagnosis of neuroendocrine tumours. It has been suggested that high activities of such an agent may have a therapeutic effect. The aims of this study were to assess toxicity and to determine if there had been evidence of efficacy. Eight patients with known disseminated neuroendocrine tumours were enrolled in the study; six had carcinoid tumours, one had a medullary cell carcinoma of the thyroid and one patient had a malignant gastrinoma. Between 1.3 and 4.6 GBq of 111In-Octreotide were administered to each patient for up to five administrations over 12 months. A total of 23 administrations were given. Tests of vital signs, renal, liver and endocrine function as well as haematological markers were taken before and after treatment. The treatment was well tolerated with only one patient suffering from a sensation of flushing during the infusion but no changes in vital sings. There was a transient (up to 48 h) drop in circulating lymphocytes in four patients and platelets in two patients; no supportive therapy was needed. One patient with severe renal impairment had a slight reduction in glomerular filtration rate. We conclude that high-activity 111In-Octreotide is well tolerated with low toxicity and can be considered for use in patients with disseminated neuroendocrine tumours. Further work is now being performed to assess efficacy.

Parathyroid imaging with Tc-99m sestamibi planar and SPECT scintigraphy.

Technetium-99m sestamibi planar and single-photon-emission computed tomographic scintigraphy is useful in the diagnosis of parathyroid gland disease. To understand the various patterns of parathyroid disease, it is important to understand parathyroid embryology and anatomy. The spectrum of parathyroid disease demonstrated with Tc-99m sestamibi scintigraphy includes eutopic disease, ectopic disease, solitary adenoma, double or multiple adenomas, cystic adenoma, lipoadenoma, multiple endocrine neoplasia, hyperfunctioning parathyroid transplant, entities with atypical washout, and nonparathyroid entities that take up Tc-99m sestamibi. The diagnosis of parathyroid tumors with Tc-99m sestamibi scintigraphy is based on the difference in clearance rates between the thyroid and diseased parathyroid glands, and any condition that interferes with radiotracer clearance will limit the effectiveness of the study. The technique is most clearly indicated for the preoperative evaluation of recurrent or persistent hyperparathyroidism, but it is increasingly being used before the initial surgical exploration as well. Subtraction Tc-99m sestamibi and iodine-123 scintigraphy may be helpful in difficult cases. Parathyroid hyperplasia, multisite parathyroid disease, and concomitant thyroid and parathyroid disease remain potential hurdles for this scintigraphic technique, and optimal handling of these problems still relies heavily on the skill and experience of the endocrine surgeon.