Diagnosis Of Gastroenteropancreatic Neuroendocrine Tumors Research Articles

GEP-NET radiomics: a systematic review and radiomics quality score assessment.

The number of radiomics studies in gastroenteropancreatic neuroendocrine tumours (GEP-NETs) is rapidly increasing. This systematic review aims to provide an overview of the available evidence of radiomics for clinical outcome measures in GEP-NETs, to understand which applications hold the most promise and which areas lack evidence. PubMed, Embase, and Wiley/Cochrane Library databases were searched and a forward and backward reference check of the identified studies was executed. Inclusion criteria were (1) patients with GEP-NETs and (2) radiomics analysis on CT, MRI or PET. Two reviewers independently agreed on eligibility and assessed methodological quality with the radiomics quality score (RQS) and extracted outcome data. In total, 1364 unique studies were identified and 45 were included for analysis. Most studies focused on GEP-NET grade and differential diagnosis of GEP-NETs from other neoplasms, while only a minority analysed treatment response or long-term outcomes. Several studies were able to predict tumour grade or to differentiate GEP-NETs from other lesions with a good performance (AUCs 0.74-0.96 and AUCs 0.80-0.99, respectively). Only one study developed a model to predict recurrence in pancreas NETs (AUC 0.77). The included studies reached a mean RQS of 18%. Although radiomics for GEP-NETs is still a relatively new area, some promising models have been developed. Future research should focus on developing robust models for clinically relevant aims such as prediction of response or long-term outcome in GEP-NET, since evidence for these aims is still scarce. • The majority of radiomics studies in gastroenteropancreatic neuroendocrine tumours is of low quality. • Most evidence for radiomics is available for the identification of tumour grade or differentiation of gastroenteropancreatic neuroendocrine tumours from other neoplasms. • Radiomics for the prediction of response or long-term outcome in gastroenteropancreatic neuroendocrine tumours warrants further research.

The New Radiolabeled Peptide 99mTcEDDA/HYNIC-TOC: Is It a Feasible Choice for Diagnosing Gastroenteropancreatic NETs?

Simple SummaryGastroenteropancreatic neuroendocrine tumors are a group of heterogenous tumors that account for about 60% of the neuroendocrine tumors diagnosed nowadays. They possess the capability to synthesize and secrete peptides and hormones that lead to their characteristic syndromes. One of their main characteristics is the expression of somatostatin receptors, which makes them appropriate for diagnosis based on radiolabeled somatostatin analogs scintigraphy and PET/CT. This retrospective monocentric study was conducted to determine the suitability of 99mTcEDDA/HYNIC-TOC scintigraphy in diagnosis and management of gastroenteropancreatic neuroendocrine tumors, in comparison with other available radiotracers. We examined 173 patients referred to our clinic for a 99mTcEDDA/HYNIC-TOC scan and, based on the obtained results, we estimated the sensitivity, specificity, accuracy, and positive and negative predictive values of the method. Our results confirm the utility of 99mTcEDDA/HYNIC-TOC in the management and follow-up of patients suffering from gastroenteropancreatic neuroendocrine tumors, especially in centers that do not benefit from PET/CT equipment or 68Ga-DOTA-peptides.(1) Background: The aim of our study is to reveal the advantages and limitations of the use of 99mTcEDDA/HYNIC-TOC (Tektrotyd®, Polatom) in the diagnosis of gastroenteropancreatic neuroendocrine tumors and to compare our results with the values obtained for 111In-pentetreotide and 68Ga-DOTA-peptides, routinely used in medical practice. (2) Methods: This retrospective monocentric study included 173 patients with gastroenteropancreatic neuroendocrine tumors who underwent 99mTcEDDA/HYNIC-TOC scans as part of their clinical management. The examination protocol included a whole-body scan acquired 2 h after the radiotracer’s administration, with the SPECT/CT performed 4 h post-injection. Physiological and abnormal uptake were established by two experienced physicians and, based on the obtained results, sensitivity, specificity, accuracy, positive predictive value and negative predictive value were calculated. (3) Results: Our method presented a sensitivity of 90.5%, a specificity of 71.9%, and an accuracy of 84.3%, with a positive predictive value of 86.7% and a negative predictive value of 78.8%. (4) Conclusions: 99mTc-EDDA/HYNIC-TOC, a receptor-based radiopharmaceutical, could represent a competitor for 68Ga-labeled peptides in the diagnosis and management of patients with gastroenteropancreatic neuroendocrine tumors. Our results show a lower sensitivity (90.5%) than 68Ga-DOTA-peptides, but with great specificity, accuracy, positive, and negative predictive values.

A natural history of gastroenteropancreatic neuroendocrine tumors evaluated at a tertiary cancer center: An observational study of 2,067 cases.

508 Background: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are the second most prevalent digestive cancer and are increasing in incidence. With relatively indolent tumor growth, survival is often long, even for patients with metastatic disease. However, few studies have assessed long-term survival. Therefore, we analyzed the overall survival (OS) of a cohort of GEP-NET patients at a tertiary cancer center from 2000-2015. Methods: 2,707 patients with a pathologic diagnosis of GEP-NET were identified. 640 patients presented for second-opinion visits and were excluded, leaving 2,067 patients, of whom, 2,053 had vital status data for analysis. Primary sites included jejunum/ileum (small bowel), pancreas, gastric, colorectum, appendix, duodenum, and unknown. OS time was calculated from the date of pathologic diagnosis to the date of last follow-up or death. The reverse Kaplan-Meier method was used to calculate follow-up time. Vital status was identified through linkage to the Florida Cancer Registry. Kaplan-Meier (KM) curves and log-rank test were used for OS analyses. Results: The median age of the cohort was 60.7 years. The median follow-up time was 148.9 months (12.4 years). 1,431 (69.2%) patients presented with distant metastatic disease. Most patients, 1,351 (65.5%), underwent treatment at another facility before presentation. The median OS was 132.2 months (11.0 years) for the cohort and was 108.0 and 245.5 months for patients presenting with and without metastasis, respectively (p < 0.001). For metastatic patients, unknown primary tumor site was associated with the worst median OS (55 months), followed by rectal (77 months), gastric (84 months) and pancreatic (85 months; p < 0.001). Duodenal and small bowel had the longest median OS at 147 and 143 months, respectively. Surgery for metastatic disease had an OS benefit (155.7 months) compared to no surgery (98.3 months). Conclusions: In a large cohort of predominantly metastatic GEP-NET patients with extended follow-up time, median OS was over 11 years and 9 years for patients with metastatic disease. These results suggest that OS at a tertiary cancer center may be greater than historical national administrative analyses when given adequate follow-up time, which is important to avoid bias in survival estimates.[Table: see text]

Epidemiologic Trends of and Factors Associated With Overall Survival for Patients With Gastroenteropancreatic Neuroendocrine Tumors in the United States

Although the incidence and prevalence of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) have been thought to have increased during the past decades, updated epidemiologic and survival data are lacking. To conduct an epidemiologic and survival analysis of the largest cohort of patients with GEP-NETs using the latest data and to establish a novel nomogram to predict the survival probability of individual patients with GEP-NETs. In this cohort study, 43 751 patients with GEP-NETs diagnosed from January 1, 1975, to December 31, 2015, were identified from the Surveillance, Epidemiology, and End Results Program. Associated data were used for epidemiologic and survival analysis, as well as the establishment and validation of a nomogram to predict the survival probability of individual patients with GEP-NETs. The study cutoff date was December 31, 2018. Statistical analysis was performed from February 1 to April 30, 2020. Incidence, factors associated with overall survival, and a nomogram model for patients with GEP-NETs. A total of 43 751 patients received a diagnosis of GEP-NETs from 1975 to 2015 (22 398 women [51.2%], 31 976 White patients [73.1%], 7097 Black patients [16.2%], 3207 Asian and Pacific Islander patients [7.3%], 270 American Indian and Alaska Native patients [0.6%], and 4546 patients of unknown race [10.4%]; mean [SD] age at diagnosis, 58 [15] years). The age-adjusted incidence rate of GEP-NETs increased 6.4-fold from 1975 to 2015 (annual percentage change [APC], 4.98; 95% CI, 4.75-5.20; P < .001). Furthermore, among site groups, the incidence of GEP-NETs in the rectum increased most significantly (APC, 6.43; 95% CI, 5.65-7.23; P < .001). As for stage and grade, the incidence increased the most in localized GEP-NETs (APC, 6.53; 95% CI, 6.08-6.97; P < .001) and G1 GEP-NETs (APC, 18.93; 95% CI, 17.44-20.43; P < .001). During the study period, the mean age at diagnosis for localized disease increased by 9.0 years (95% CI, 3.3-14.7 years; P = .002), which remained unchanged for regional and distant cases. On multivariable analyses, age, sex, marital status, and tumor size, grade, stage, and site were significantly associated with overall survival for patients with GEP-NETs (eg, patients with distant vs localized disease: hazard ratio, 10.32; 95% CI, 8.56-12.43; G4 vs G1 GEP-NET: hazard ratio, 6.37; 95% CI, 5.39-7.53). Furthermore, a nomogram comprising age, size, grade, stage, and site was established to predict the 3-year and 5-year survival probability, with the concordance indexes of 0.893 (95% CI, 0.883-0.903) for the internal validations and 0.880 (95% CI, 0.866-0.894) for the external validations. The receiver operating characteristic curve demonstrated that the nomogram exhibited better discrimination power than TNM classification (area under the curve for 3-year overall survival, 0.908 vs 0.795; for 5-year overall survival, 0.893 vs 0.791). In this study, the incidence and prevalence of GEP-NETs have continued to increase over 40 years, especially among patients with rectal GEP-NETs. In addition, this study suggests that a nomogram with 5 prognostic parameters may accurately quantify the risk of death among patients with GEP-NETs, indicating that it has satisfactory clinical practicality.

Time from first tumor manifestation to diagnosis in patients with GEP-NET: Results from a large German tertiary referral center.

Patients with neuroendocrine tumors (NET) often go through a long phase between onset of symptoms and initial diagnosis.Assessment of time to diagnosis and pre-clinical pathway in patients with gastroenteropancreatic NET (GEP-NET) with regard to metastases and symptoms.Retrospective analysis of patients with GEP-NET at a tertiary referral center from 1984 to 2019; inclusion criteria: Patients ≥18 years, diagnosis of GEP-NET; statistical analysis using non-parametrical methods.Four hundred eighty-six patients with 488 tumors were identified; median age at first diagnosis (478/486, 8 unknown) was 59 years; 52.9% male patients. Pancreatic NET: 143/488 tumors; 29.3%; small intestinal NET: 145/488 tumors, 29.7%. 128/303 patients (42.2%) showed NET specific and 122/486 (25%) patients other tumor-specific symptoms. 222/279 patients had distant metastases at initial diagnosis (187/222 liver metastases). 154/488 (31.6%) of GEP-NET were incidental findings. Median time from tumor manifestation (e.g., symptoms related to NET) to initial diagnosis across all entities was 19.5 (95% CI: 12–28) days. No significant difference in patients with or without distant metastases (median 73 vs 105 days, P = .42).A large proportion of GEP-NET are incidental findings and only about half of all patients are symptomatic at the time of diagnosis. We did not find a significant influence of the presence of metastases on time to diagnosis, which shows a large variability with a median of <30 days.

1187P Characterization of the gastroenteropancreatic neuroendocrine tumour patient journey

With increasing incidence and prevalence of gastroenteropancreatic neuroendocrine tumours (GEP-NETs), there is a need to identify inefficiencies in patient management. To provide a view of the journey for patients with GEP-NETs, healthcare professionals (HCPs) and patients from the USA and EU4 (France, Italy, Spain, UK) were interviewed with responses analyzed to determine consensus views. Fifty-four interviews were completed (49 HCPs, five patients). Time to first diagnosis of GEP-NET takes 5–7 years on average and misdiagnosis is common. Multidisciplinary team (MDT) structure and dynamics vary by practice type, institution, and country. In academic settings, GEP-NET is discussed in gastroenterology and/or hepatobiliary tumour boards, but centres with large case volume may hold NET-specific MDTs. Nuclear medicine physicians are increasingly involved in MDTs across many institutions, where they are consulted on patient eligibility for peptide receptor radionuclide therapy (PRRT). In the USA, medical oncologists are the primary treatment decision-makers, while gastroenterologists and endocrinologists are more involved in decisions in Europe, depending on tumour localization. Surgery-ineligible first-line cases are widely managed with somatostatin analogue therapy, and systemic options including PRRT and liver-directed therapies are provided for patients with metastatic disease. While PRRT is commonly used in second-line for low grade, well-differentiated tumors, it can be considered in first-line for patients with poorly differentiated fast-growing, somatostatin receptor-positive tumours. Treatment sequencing depends highly on physician attitudes and logistical barriers. HCP follow-up varies according to treatment and experience with GEP-NET. The rarity of GEP-NET, along with its late diagnosis and misdiagnosis can lead to complexities and uncertainty in sequencing when selecting the right therapy. Differences in management decision vary amongst institutions and countries, and the involvement of nuclear medicine physicians in the decision-making process of MDTs can improve awareness to availability of a treatment option such as PRRT.

Trends in diagnosis of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) in India: A report of multicenter data from a web-based registry.

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare tumors. We report data of 407 GEP-NET cases from a neuroendocrine tumor (NET) registry in India. The AP-NET registry is an open-label, multicenter, longitudinal observational registry of patients with GEP-NETs in which six tertiary care oncology centers contributed data. Data was prospectively entered in a dedicated computerized database and was reviewed retrospectively. The patients were divided into three cohorts-those diagnosed from 2001 to 2005, from 2006 to 2010, and from 2011 to 2016. Of the 407 cases registered, 37 were in Cohort I, 136 in Cohort II, and 234 in Cohort III. Majority were symptomatic with only 98 patients (24.0%) asymptomatic. The most common presentation of non-functional tumors was abdominal pain (42.4%), while functional tumors presented most commonly with carcinoid syndrome. Use of DOTA-PET, introduced in 2011, has increased evaluation in 33.3% patients in Cohort III. The most common primary site was pancreas in all three cohorts. Male preponderance (58.3%) was seen. Histopathological grading was obtained in 230 (56.5%) patients-118 (29%) Grade I, 74 (18.2%) Grade II, and 36 (8.8%) Grade III NET. This report highlights changing trends in the diagnosis and reporting of NETs over the last 15years.

Sex comb on midleg like-2 is a novel specific marker for the diagnosis of gastroenteropancreatic neuroendocrine tumors.

Sex comb on midleg like-2 (SCML2) is a polycomb-group protein that encodes transcriptional repressors essential for appropriate development in the fly and in mammals. On the basis of previous findings, the present study aimed to explore the possibility of developing SCML2 into a new diagnostic marker for gastroenteropancreatic neuroendocrine tumors (GEP-NETs). A total of 64 paired GEP-NET tissues and adjacent non-tumorous tissues were obtained from patients who had undergone surgical resection between January 2009 and January 2014, and the expression of SCML2 and two neuroendocrine markers, namely synaptophysin (Syn) and chromogranin A (CgA), in the tissues was assessed by immunohistochemistry. Strong SCML2 staining was observed predominantly in the cell nuclei of GEP-NET tissues, and the overall expression rate and staining intensity of SCML2 were higher than those of Syn or CgA, respectively. Spearman rank correlation analysis demonstrated that SCML2 was not correlated with either Syn or CgA, while the combined detection of SCML2 with Syn or with CgA increased the diagnostic sensitivity to 100%. SCML2 expression in GEP-NETs was associated with several clinicopathological parameters, such as histological type, tumor grade, depth of invasion and clinical stage. Kaplan-Meier survival curves revealed that patients with higher SCML2 expression had lower survival rates than those with lower expression levels, while Cox proportional hazards regression analysis revealed that SCML2 was not an independent prognostic factor for GEP-NET patients. Therefore, SCML2 may have potential as a specific marker for joint use with other markers to improve the diagnostic efficiency of GEP-NETs.

Current treatment options for gastroenteropancreatic neuroendocrine tumors with a focus on the role of lanreotide.

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a large and very diverse group of neoplasms. Clinical presentation of NETs depends on the site of the primary tumor and whether the tumor is functioning (i.e., secreting peptides or neuroamines that produce symptoms). The diagnosis of GEP-NET is further complicated by symptomatic differences that occur depending on the type of secreted peptide or neuroamine. Due to their heterogeneity and unique characteristics, early diagnosis of GEP-NETs is difficult, which increases the likelihood of metastatic disease and reduces the scope of therapeutic possibilities. Thus, a multidisciplinary approach for the treatment of GEP-NETs is necessary. This review is the result of presentations that were delivered during an expert meeting on the treatment of GEP-NETs supported by Ipsen. We summarize the current knowledge on the epidemiology, incidence, diagnosis, and treatment of GEP-NETs. We examined the role of the somatostatin analog (SSA) lanreotide and the impact of the data from the recently published, randomized, double-blind, placebo-controlled CLARINET study (Controlled study of Lanreotide Antiproliferative Response In Neuroendocrine Tumors) on disease management. We also review the recent treatment options and recommendations for GEP-NETs.

The state of the art of imaging in gastroenteropancreatic neuroendocrine tumors

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are neoplasms presenting unpredictable and unusual biologic behavior that causes many clinical challenges. NETs can produce a variety of metabolically active substances (hormones and amines) leading to distinct clinical syndromes. This review will discuss the imaging techniques for the diagnosis of GEP-NETs including ultrasonography, CT, MRI and ultrasound endoscope. In this article, Gallium-68 labeled peptide binding to G protein coupled receptor including SSTR, CCKR1 and GLP1R is addressed, and the application of Gallium-68 labeled somatostin analogues and PET-CT for diagnosis of GEP-NETs is evaluated. In conclusion, Gallium-68 labeled peptide and molecular imaging will play important roles in diagnosis, prognosis and therapeutic strategy development of GEP-NETs.

Tumeurs neuroendocrines du tube digestif et du pancréas : ce que le pathologiste doit savoir et doit faire en 2014

The diagnostic management of a possible case of gastroenteropancreatic neuroendocrine tumor has much changed in the last 10 years. It is now made of four successive steps. The first step is the positive diagnosis, i.e. the definitive identification of the neuroendocrine nature of the tumor: it relies on morphological and immunohistochemical arguments; several national and international recommendations have now clarified the immunohistochemical arguments necessary for, and sufficient to make a diagnosis of gastroenteropancreatic neuroendocrine tumor. The second step is the determination of the grade, essential for the evaluation of the risk of progression: it relies on the determination of the proliferative capacities, according to the proposals of the European NeuroEndocrine Tumor Society (ENETS), later adopted by WHO in 2010. The third step is the histoprognostic classification, which must use a standardized terminology: it is required to use the specific classification proposed in 2010 by WHO in the framework of the revision of the classifications of digestive tumors. The last step is staging, which relies on the use of one of the existing TNM classifications, that, official, proposed by UICC/AJCC or that proposed by ENETS. The minimal informations, which must be present in the pathological report have been stated by the Société Française de Pathologie, at the request of the French National Cancer Institute.

Dual Tracer Functional Imaging of Gastroenteropancreatic Neuroendocrine Tumors Using 68Ga-DOTA-NOC PET-CT and 18F-FDG PET-CT

This study aimed to compare the diagnostic performance of Ga-DOTANOC PET/CT with F-FDG PET/CT in the patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Data of 51 patients with definite histological diagnosis of GEP-NET who underwent both Ga-DOTA-NOC PET-CT and F-FDG PET-CT within a span of 15 days were selected for this retrospective analysis. Sensitivity, specificity, and predictive values were calculated for Ga-DOTA-NOC PET-CT and F-FDG PET-CT, and results were compared both on patientwise and regionwise analysis. Ga-DOTA-NOC PET-CT is superior to F-FDG PET-CT on patientwise analysis (P < 0.0001). On regionwise analysis, Ga-DOTA-NOC PET-CT is superior to F-FDG PET-CT only for lymph node metastases (P < 0.003). Although Ga-DOTA-NOC PET-CT detected more liver and skeletal lesions compared with F-FDG PET-CT, the difference was not statistically significant. In addition, the results of combined imaging helped in selecting candidates who would undergo the appropriate mode of treatment, whether octreotide therapy or conventional chemotherapy Ga-DOTA-NOC PET-CT seems to be superior to F-FDG PET-CT for imaging GEP-NETs. However, their role seems to be complementary because combination of Ga-DOTA-NOC PET-CT and F-FDG PET-CT in such patients helps demonstrate the total disease burden and segregate them to proper therapeutic groups.

Current Trends of the Incidence and Pathological Diagnosis of Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs) in Korea 2000-2009: Multicenter Study

PurposeAs a result of various independently proposed nomenclatures and classifications, there is confusion in the diagnosis and prediction of biological behavior of gastroenteropancreatic neuroendocrine tumors (GEP-NETs). A comprehensive nationwide study is needed in order to understand the biological characteristics of GEP-NETs in Korea.Materials and MethodsWe collected 4,951 pathology reports from 29 hospitals in Korea between 2000 and 2009. Kaplan-Meier survival analysis was used to determine the prognostic significance of clinicopathological parameters.ResultsAlthough the GEP-NET is a relatively rare tumor in Korea, its incidence has increased during the last decade, with the most significant increase found in the rectum. The 10-year survival rate for well-differentiated endocrine tumor was 92.89%, in contrast to 85.74% in well differentiated neuroendocrine carcinoma and 34.59% in poorly differentiated neuroendocrine carcinoma. Disease related death was most common in the biliary tract (62.2%) and very rare in the rectum (5.2%). In Kaplan-Meier survival analysis, tumor location, histological classification, extent, size, mitosis, Ki-67 labeling index, synaptophysin expression, lymphovascular invasion, perineural invasion, and lymph node metastasis showed prognostic significance (p<0.05), however, chromogranin expression did not (p=0.148). The 2000 and 2010 World Health Organization (WHO) classification proposals were useful for prediction of the prognosis of GEP-NET.ConclusionThe incidence of GEP-NET in Korea has shown a remarkable increase during the last decade, however, the distribution of tumors in the digestive system differs from that of western reports. Assessment of pathological parameters, including immunostaining, is crucial in understanding biological behavior of the tumor as well as predicting prognosis of patients with GEP-NET.

Comment on: Somatostatin receptor SPECT

Comment on: Somatostatin receptor SPECT

The Role of Nuclear Medicine in Imaging and Therapy of Neuroendocrine Tumors

Neuroendocrine tumors (NET’s) constitute a heterogeneous group of tumors characterized by the simultaneous expression of specific marker proteins and cell type-specific hormonal products. Metaiodobenzyluanidine (MIBG), labelled with 131 I or 123 I, and 111 In-pentetreotide (Octreoscan) are the radiopharmaceuticals of choice in the current clinical practice. Positron emitting radiopharmaceuticals that are used in PET imaging are 18 F-fluorodeoxyglucose ( 18 F-FDG), 18 F-fluorodopamine ( 18 F-DOPA), 11 C-hydroxy-tryptophan ( 11 C-HTP), and Gallium-68 ( 68 Ga-DOTATATE or DOTATOC). In diagnosis of gastroenteropancreatic neuroendocrine tumors (GEPs) Octreoscan is the preferred imaging method because of its high sensitivity. 131 Ι/ 123 Ι-MIBG scintigraphy is useful to characterize and locate intra-adrenal (pheochromocytomas) and extra-adrenal paragangliomas. Octreoscan has also high accuracy for extra-adrenal paragangliomas. 18 F-FDG-PET or PET/CT seems to be useful in detecting the pheochromocytomas and GEPs that fail to concentrate MIBG and Octreocan. 123 I-MIBG scintigraphy combined with urine analysis of catecholamine metabolites is the most sensitive indicator of neuroblastoma. In diagnosis of small cell lung cancer and pituitary adenomas Octreoscan has a high sensitivity. On the contrary, in medullary thyroid cancer the sensitivity of Octreoscan and 131 Ι/ 123 Ι-MIBG is low but sensitivity of 18 F-FDG PET or PET/CT and 68 Ga-DOTATATE and DOTATOC PET or PET/CT seems to be higher. With the introduction of 131 I-MIBG and octreotide labelled with several radioisotopes, the field of treatment with radionuclides has been extended to a wide range of NETs. 111 In-DTPA-Octreotide firstly was used in some clinical trials but recent advances in somatostatin analogues have paved the way to the development of octreotate, which can be labelled with both 177 Lu and 90 Y radionuclides.

The diagnostic and prognostic value of chromogranin A and synaptophysin in gastroenteropancreatic neuroendocrine tumors

Objective To explore the expression and clinical significance of chromogranin A (CgA) and synaptophysin (Syn) in gastroenteropancreatic neuroendocrine tumors (GEP-NET).Methods The data of sixty-six GEP-NET patients treated in the First Affiliated Hospital of Nanjing Medical University were collected between Jan.2003 and May 2009.The expression of CgA and Syn in the tissue of GEP-NET was detected by immunohistochemistry, and its association with clinicopathological characteristics and prognosis of GEP-NET were analyzed.Results In these 66 patients,the positive rate of Syn (87.9％,58/66) was higher than that of CgA (71.3％,47/66,x2 =5.63,P=0.02).CgA and Syn were simultaneously expressed in 64.6％ patients (42/66).In the tissues of GEP-NET,the expression of CgA was related with lymph node metastasis and TNM stages,not related with patients' gender,age,tumor location,function,degree of differentiation,tumor size,infiltration and distant metastasis. Syn was not related with all the above clinicopathological parameters.Three-year survival rate in CgA negative group (47％) was significantly lower than that in positive group (78％,x2 =0.00,P=0.01).Conclusions Syn was more sensitive than CgA in the diagnosis of GEP-NET.CgA in some extent indicates the prognosis of GEP-NET. Key words: Gastrointestinal neoplasms; Pancreatic neoplasms; Carcinoma, neuroendocrine; Synapsins; Chromogranins; Prognosis

Delay in the diagnosis of multiple endocrine neoplasia type 1: typical symptoms are frequently overlooked

The morbidity and mortality of individuals with multiple endocrine neoplasia type 1 (MEN1) can be reduced by early diagnosis of MEN1 and related endocrine tumors. To find factors contributing to early diagnosis, we collected clinical information on MEN1 patients through a MEN study group, "MEN Consortium of Japan" and analyzed the time of initial symptom-dependent detection of parathyroid tumors, gastro-entero-pancreatic neuroendocrine tumors (GEPNETs) and pituitary tumors, and that of tumor detection-dependent MEN1 diagnosis in 560 patients. Main tumors were identified up to 7.0 years after symptoms appeared and there was no difference in age at the diagnosis of GEPNETs alone between probands and family members. In patients with typical symptoms (peptic ulcers, urolithiasis, fasting hypoglycemia, bone fracture/loss and amenorrhea), the mean interval between symptom manifestation and tumor detection was extended up to 9.6 years. In particular, 21.7% (5/23) of patients with amenorrhea were diagnosed with pituitary tumors in under one year. In patients with peptic ulcers (from parathyroid tumors or GEPNETs) and urolithiasis (from parathyroid tumors), the interval was positively correlated with age at tumor detection. The interval between tumor detection and MEN1 diagnosis was also prolonged to approximately four years in patients with fasting hypoglycemia (from GEPNETs) and amenorrhea. A substantial delay in the diagnosis of symptom-related tumors and subsequent MEN1 and inadequate screening of GEPNETs in family members were indicated. A greater understanding of MEN1 may assist medical practitioners to make earlier diagnoses, to share patients' medical information and to give family members sufficient disease information.

Is the combination of chromogranin A and pancreatic polypeptide serum determinations of interest in the diagnosis and follow-up of gastro-entero-pancreatic neuroendocrine tumours?

IntroductionChromogranin A (CgA) is the principal tumour marker for gastroenteropancreatic neuroendocrine tumours (GEPNET). Combining serum CgA and pancreatic polypeptide (PP) levels may increase the sensitivity of tumour markers in the diagnosis of GEPNET. Objectives(1) To evaluate the sensitivity of PP and CgA in GEPNET. (2) To compare changes in serum CgA and PP levels with the morphological evolution of the tumours. Patients and methodsSixty-six pancreatic and 49 gastrointestinal NET, with at least one serum determination of CgA and PP at the same time were retrieved from an institutional data base. Secondly, the variations in serum CgA or PP at successive determinations were compared to Response Evaluation Criteria in Solid Tumours (RECIST) criteria in 57 patients (112 follow-up visits) with high serum CgA levels and in 21 patients (37 follow-up visits) with high serum PP levels. ResultsAmong the 115 patients included in the study group, an increase in serum CgA (normal <98μg/L) or PP (normal <100pmol/L) was found in respectively 79 (69%) and 36 (31%) cases. Seven patients had normal CgA and elevated PP levels. Both markers were significantly more elevated in metastatic disease (74% versus 51% for CgA and 37% versus 18% for PP). The concordance rates between serum markers and RECIST criteria were 51% for CgA and 54% for PP. ConclusionsSerum PP determination identify few false-negative results of serum CgA determination in GEPNET. Our study does not validate the use of CgA or PP as surrogate markers for detecting changes in tumour burden.

Ciblage des récepteurs de la somatostatine dans les tumeurs neuroendocrines gastroentéropancréatiques (TNE-GEP) : quels radiotraceurs pour quelles tumeurs ?

Topographic and functional imaging hold a key position in endocrine oncology. In vivo somatostatin receptor scintigraphy using Indium-111 labeled DTPA-octreotide, a tracer with preferential affinity for the somatostatin receptor subtype 2 (sst2), is the gold-standard for initial diagnosis of gastroenteropancreatic neuroendocrine tumours (GEPNETs). Due to the detection limits of scintigraphy, other metabolic imaging modalities are required. Positron emission topography (PET) offers whole body scanning, facilitates tumour localization, and assesses the metastasis statement of the tumour. 18F-FDG is the most frequent radiotracer used in clinical practice because of its availability, but its interest is demonstrated only in undifferentiated GEPNETs. More recently, 18F-DOPA PET showed a high sensitivity in particular in carcinoid tumours detection. PET using different 68Ga-labeled-somatostatin analogs with high affinity for sst2 displayed better results than SRS in GEPNETs primary tumour and metastasis detection, especially when fusion with TDM images was performed. Using similar metabolic targets, peptide receptor radionuclide therapy (PRRT) with 177Lu-octreotate and 90Y-DOTA-TOC, is indicated in disseminated GEPNETs forms with an efficiency of 30 % and a minor toxicity.