[Gastroenteropancreatic neuroendocrine neoplasms-Heterogeneity, management and perspectives of treatment and research]. / Gastroenteropankreatische neuroendokrine Neoplasien ­ Heterogenität, Management und Perspektiven der Versorgung und Forschung.

The term neuroendocrine neoplasms (NEN) encompasses a molecularly and biologically very heterogeneous group of tumors, which have in common their origin in neuroendocrine cells. The also very heterogeneous subgroup of gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) is the best classified and investigated group. This article provides a systematic review of the current classification, diagnostics and treatment options of GEP-NEN. In order to achieve a better overview, it was consciously decided not to use an approach based on the primary localization. Instead, a thematic organization according to classification, clinical phenotype, diagnostics and treatment was chosen.

[Nutrition in type 2 diabetes mellitus]. / Ernährung bei Diabetes mellitus Typ 2.

The increasing incidence of metabolic diseases, such as type 2 diabetes mellitus, poses a major problem for the healthcare system. Healthy food habits represent an important therapeutic measure to prevent health sequelae, such as cardiovascular diseases. According to recent data these are less due to individual dietary components and more to the composition of nutrition. A positive effect on glucose and fat metabolism in type 2 diabetes has been confirmed for various forms of nutrition. In addition to the type of nutrition, the so-called glycemic index of foodstuffs is also decisive for blood glucose control. Additionally, beneficial effects for particular foodstuffs, such as coffee, could be determined in patients with diabetes.

[Thyroid and pregnancy]. / Schilddrüse und Schwangerschaft.

During pregnancy thyroid hormones have profound effects on embryonal/fetal development and maternal health. Therefore, thyroid gland disorders should be immediately diagnosed and adequately treated. Pregnancy-specific physiological alterations during pregnancy cause changes in the reference interval for thyroid-stimulating hormone levels and trimester-specific thresholds must be taken into account. This article summarizes the most important diagnostic and therapeutic aspects before, during and after pregnancy. With reference to the period prior to pregnancy, the article discusses iodide supplementation, preconceptional examination of thyroid gland metabolism and the importance of thyroid gland functional disorders for fertility and fulfilling the desire to have children. With a view to the period during pregnancy, the effect of hypothyroxinemia, hypothyroidism, and hyperthyroidism as well as the effects of their treatment on the development of the child are explained. Finally, a description is given of what must be paid attention to in the breast-feeding period and in postpartum thyroiditis.

[Late effects following childhood cancer treatment : A special challenge for transition medicine]. / Spätfolgen einer Krebsbehandlung im Kindes- und Jugendalter : Eine Herausforderung für die Transitionsmedizin.

BACKGROUND: Childhood cancer survivors are at risk of cancer- and treatment-related chronic health conditions. Since these sequelae may occur years after the end of treatment, many patients are already adults and have completed pediatric oncological care. Thus, successful transition is essential in order to ensure long-term surveillance. OBJECTIVES: The present review outlines the most frequent late effects of childhood cancer treatment. Moreover, difficulties in transition of these patients are discussed and interdisciplinary models of care are presented. RESULTS: Late effects following childhood cancer treatment occur in over two thirds of patients 30 years after the end of the oncological treatment and can affect different organs. The most frequent sequelae are endocrine disturbances, cardiac conditions, and subsequent neoplasms. Many late effects are effectively manageable if detected early. This necessitates an interdisciplinary approach as well as life-long surveillance. CONCLUSIONS: Transition from pediatric to internal medicine care as well as a change in the focus of care, shifting from relapse centered follow-up to late-effects centered surveillance, constitute a special challenge for a successful transition of long-term childhood cancer survivors. Specialized late-effects survivorship clinics offering interdisciplinary care from pediatric oncologists, specialists of internal medicine, and further disciplines enable the early diagnosis and treatment of late-effects.

Tip Design of Hemodialysis Catheters Influences Thrombotic Events and Replacement Rate.

OBJECTIVE/BACKGROUND: Central venous tunnelled hemodialysis catheters (CVTC) are used for initial vascular access in patients with renal failure. Tip design of the CVTC may play an important role in catheter function and complication rates, influencing adequate hemodialysis treatment of these patients. METHODS: This prospective, observational cohort study compared the function and complication rates of two CVTCs in patients with end stage renal disease (ESRD) within a follow-up period of 24 months. The study included patients with ESRD who received either a CVTC with a split tip (ST) or a shotgun tip (SG). All patients underwent dialysis within 24 h of intervention. Blood flow was documented initially (Qb0) and was followed up after 6 (Qb6), 12 (Qb12), and 24 (Qb24) months. Analysis of blood flow and complication rates within the follow-up period was performed by questionnaires. RESULTS: In total, 185 patients were included, of whom 93 received a ST CVTC and 92 a SG CVTC. Baseline parameters did not differ significantly between groups. CVTC blood flow was not significantly different between the two devices. Thrombolytic therapy with Alteplase was used significantly more often in the ST group (29%) than in the SG group (16%) (p < 0.05). The CVTC replacement rate was significantly higher in the ST group (19.3%) compared with the SG group (8.7%) (p < 0.05). CONCLUSIONS: The tip design of CVTC (split or shotgun) appears to be irrelevant for long-term blood flow during dialysis treatment. However, patients may benefit from SG catheters over ST catheters where replacement rates and thrombolytic treatment are concerned.

[Diabetic emergencies : Hypoglycemia, ketoacidotic and hyperglycemic hyperosmolar nonketotic coma]. / Diabetologische Notfälle : Hypoglykämie, ketoazidotisches und hyperglykämisches Koma.

The diabetic emergencies diabetic ketoacidosis (DKA), hyperglycemic hyperosmolar state (HHS) and hypoglycemia represent severe and potentially life-threatening complications of diabetes mellitus that require prompt diagnostics and treatment. Absolute or relative insulin insufficiency is characteristic of DKA und HHS along with severe dehydration. They differ by the prevalence of ketone bodies and the severity of acidosis; however, the treatment regimens are similar. In contrast, hypoglycemia is the limiting factor for achieving ambitious glucose targets. This article decribes the clinical presentation, diagnostics and emergency management of these metabolic derangements.

[Modulation of the intestinal microbiota by nutritional interventions]. / Modulation der intestinalen Mikrobiota durch Ernährungsinterventionen.

Humans live in symbiosis with billions of commensal bacteria. The so-called microbiota live on different biological interfaces such as the skin, the urogenital tract and the gastrointestinal tract. Commensal bacteria replace potentially pathogenic microbes, synthesize vitamins and ferment dietary fibre. An imbalance in the bacterial composition of the intestinal microbiota has been associated with various diseases including gut-associated disorders such as inflammatory bowel diseases, colorectal cancer and nonalcoholic fatty liver disease. Furthermore, a shift in the microbiota composition appears to be of pathophysiological relevance which renders the specific modulation of the intestinal microbiota a promising approach in the treatment of the above mentioned diseases. Our intestinal microbiota composition is mainly modulated by dietary macro- and micronutrients but also by secondary plant compounds and synthetic food additives such as emulsifiers and artificial sweeteners. Nutritional interventions with the purpose to modulate the intestinal microbiota show only limited therapeutic potential in the treatment of gut-associated disorders, which may be due to individual differences in the intestinal microbiota composition and a lack of specificity. A combination of newly established technical analytic approaches involving a machine-learning algorithm may bridge the currently existing limitations by providing a personalized, highly-specific and consequently therapeutically effective microbiota modulation.

Oxytocin's inhibitory effect on food intake is stronger in obese than normal-weight men.

BACKGROUND/OBJECTIVES: Animal studies and pilot experiments in men indicate that the hypothalamic neuropeptide oxytocin limits food intake, and raise the question of its potential to improve metabolic control in obesity. SUBJECTS/METHODS: We compared the effect of central nervous oxytocin administration (24 IU) via the intranasal route on ingestive behaviour and metabolic function in 18 young obese men with the results in a group of 20 normal-weight men. In double-blind, placebo-controlled experiments, ad libitum food intake from a test buffet was examined in fasted subjects 45 min after oxytocin administration, followed by the assessment of postprandial, reward-driven snack intake. Energy expenditure was repeatedly assessed by indirect calorimetry and blood was sampled to determine concentrations of blood glucose and hormones. RESULTS: Oxytocin markedly reduced hunger-driven food intake in the fasted state in obese but not in normal-weight men, and led to a reduction in snack consumption in both groups, whereas energy expenditure remained generally unaffected. Hypothalamic-pituitary-adrenal axis secretion and the postprandial rise in plasma glucose were blunted by oxytocin in both groups. CONCLUSIONS: Oxytocin exerts an acutely inhibitory impact on food intake that is enhanced rather than decreased in obese compared with normal-weight men. This pattern puts it in contrast to other metabolically active neuropeptides and bodes well for clinical applications of oxytocin in the treatment of metabolic disorders.

Low Impact of Urinary Cortisol in the Assessment of Hydrocortisone Replacement Therapy.

Hydrocortisone replacement therapy is a cornerstone in the treatment of adrenal insufficiency (AI). While urinary cortisol has been used as a diagnostic tool for AI, it remains unclear whether it is a useful parameter to monitor hydrocortisone replacement therapy. Aim of this study was to evaluate possible differences in cortisol metabolism between adrenal insufficient patients and healthy subjects and to assess the value of urinary cortisol in AI management. In a case-control study, urinary cortisol excretion was determined in 14 patients with primary and secondary AI receiving hydrocortisone infusions from midnight to 8:00 AM. Results were correlated with serum cortisol levels and compared to urinary values obtained from 53 healthy volunteers. Urinary cortisol excretion in healthy subjects was 14.0±7.8 µg/8 h (range: 0.24-35.4), levels did not differ between 3 groups aged 20-34 years, 35-49 years, and ≥50 years. Patients with AI receiving hydrocortisone infusions demonstrated significantly higher rates of urinary cortisol excretion (51.6±37.8 µg/8 h; range 17.1-120.0, p<0.001); the values correlated with serum cortisol levels (r(2)=0.98). Of interest, patients with secondary AI showed significantly higher serum cortisol levels after hydrocortisone infusion than those with primary AI, conceivably due to residual adrenal function. In conclusion, we showed that: (i) there is a wide inter-individual variability in urinary cortisol excretion rates; (ii) cortisol metabolism in adrenal insufficient patients differs when compared to controls; (iii) there is a strong correlation between urinary and serum cortisol levels; and (iv) urinary cortisol levels despite their variability may help to discriminate between secondary and primary adrenal insufficiency.

[Individualized treatment of osteoporosis]. / Individualisierte Therapie der Osteoporose.

Osteoporosis is the most common clinical disorder of bone metabolism. Treatment decisions should be made on an individual basis, taking into consideration the relative benefits and risks in different patient populations. Drug selection should be based on the form (primary/secondary) and severity of osteoporosis, age, sex, the specific contraindications and precautions for using the various available medications, and existing comorbidities.

[Ethical aspects of palliative medicine]. / Ethische Aspekte der Palliativmedizin.

BACKGROUND: The aim of palliative medicine is to adequately care for and attend to patients suffering from life-threatening and incurable medical conditions according to their needs. This implies that for these patients it is not a matter of dealing with diseases that can be treated separately but with their existence in the face of their approaching death. OBJECTIVE: This article investigates which ethical questions are currently prioritized for discussion in palliative medicine. METHOD: Review of the current medical and ethical literature and own reflections with a relational ethics approach that puts patient wishes at the centre of attention. RESULTS: Palliative medicine is not a "luxury medicine" but has to be considered as primary care to which every person is entitled. If there is a need for improvement of care, promoting it is an ethical obligation. In this respect the question of a "good death" is extremely complex. The term is connected to the ethics of a good life and includes the dimensions of happiness-suffering as well as meaning-futility; therefore, the best possible treatment of symptoms, most of all pain is just as important as recognizing subjective questions of meaning. Dealing with the wishes of patients, including possible wishes to die, are the starting point for elaborating palliative care measures. It is concerned with finding the right point in time for each patient individually, in their best interests and according to their wishes, at which dying should no longer be held back but for their own benefit the patient should be accompanied and supported during dying. CONCLUSION: In the current construction of palliative medicine, including its normative configuration within the law and medical ethics, the criteria which are essential for the quality of life up to death are being discussed.

[Prevention and treatment of cachexia : Exercise and nutritional therapy]. / Prävention und Behandlung der Kachexie : Bewegungs- und Ernährungstherapie.

BACKGROUND: Cachexia is a multifactorial and complex syndrome characterized by progressive functional impairment and ongoing loss in quality of life, which lead to a deterioration of the prognosis for affected patients. The prevalence of cachexia can be very high and is up to 80 % in patients with malignant tumors. OBJECTIVE: The aim of the study was to assess the relevance of exercise and nutrition in the prevention and therapy of cachexia. METHODS: An evaluation of the current literature on exercise and nutritional therapy in patients with cachexia or with advanced stage diseases where a high prevalence of cachexia is probable, was carried out. RESULTS: There is a lack of scientific evidence for the benefits of exercise in cachexia. A major problem of relevant studies was that cachexia was frequently not defined according to valid criteria; however, data indicate a benefit of exercise training in patients with advanced diseases associated with a high prevalence of cachexia. A solely nutritional intervention and dietary counselling seem to be of minimal benefit. The administration of omega 3 fatty acids is controversially discussed. CONCLUSION: Although there is a lack of data on the effects of exercise and nutritional therapy in cachexia, there is evidence for the benefits. The present data indicate the necessity for the use of a multimodal treatment including exercise, nutritional and pharmacological therapy in cachexia. There is a great necessity for prospective studies.

The corticotrophin-releasing factor/urocortin system regulates white fat browning in mice through paracrine mechanisms.

OBJECTIVES: The corticotrophin-releasing factor (CRF)/urocortin system is expressed in the adipose tissue of mammals, but its functional role in this tissue remains unknown. METHODS: Pharmacological manipulation of the activity of CRF receptors, CRF1 and CRF2, was performed in 3T3L1 white pre-adipocytes and T37i brown pre-adipocytes during in vitro differentiation. The expression of genes of the CRF/urocortin system and of markers of white and brown adipocytes was evaluated along with mitochondrial biogenesis and cellular oxygen consumption. Metabolic evaluation of corticosterone-deficient or supplemented Crhr1-null (Crhr1(-/-)) mice and their wild-type controls was performed along with gene expression analysis carried out in white (WAT) and brown (BAT) adipose tissues. RESULTS: Peptides of the CRF/urocortin system and their cognate receptors were expressed in both pre-adipocyte cell lines. In vitro pharmacological studies showed an inhibition of the expression of the CRF2 pathway by the constitutive activity of the CRF1 pathway. Pharmacological activation of CRF2 and, to a lesser extent, inhibition of CRF1 signaling induced molecular and functional changes indicating transdifferentiation of white pre-adipocytes and differentiation of brown pre-adipocytes. Crhr1(-/-) mice showed increased expression of CRF2 and its agonist Urocortin 2 in adipocytes that was associated to brown conversion of WAT and activation of BAT. Crhr1(-/-) mice were resistant to diet-induced obesity and glucose intolerance. Restoring physiological circulating corticosterone levels abrogated molecular changes in adipocytes and the favorable phenotype of Crhr1(-/-) mice. CONCLUSIONS: Our findings suggest the importance of the CRF2 pathway in the control of adipocyte plasticity. Increased CRF2 activity in adipocytes induces browning of WAT, differentiation of BAT and is associated with a favorable metabolic phenotype in mice lacking CRF1. Circulating corticosterone represses CRF2 activity in adipocytes and may thus regulate adipocyte physiology through the modulation of the local CRF/urocortin system. Targeting CRF receptor signaling specifically in the adipose tissue may represent a novel approach to tackle obesity.

A pitfall in diagnosing Cushing's disease: ectopic ACTH-producing pituitary adenoma in the sphenoid sinus.

PURPOSE: To show a rare case of Cushing's disease and possible cause of failed transsphenoidal surgery. METHOD: We report on a 50-year-old woman suffering from ACTH-dependent Cushing's syndrome. Endocrinological work-up including low-dose/high-dose dexamethasone test (Liddle-test) and CRH test were clearly compatible with pituitary origin. Although an MRI showed no pituitary tumor, CRH-stimulated petrosal sinus sampling revealed a significant central-peripheral gradient in ACTH concentrations, rendering Cushing's disease very likely. The patient underwent transsphenoidal surgery with negative exploration of the pituitary gland. After intraoperative re-evaluation of the preoperative MRI, a "polyp" at the bottom of the sphenoid sinus was identified. The intraoperative microscopic aspect as well as instantaneous sections and cytology of a biopsy confirmed an adenoma, which was then removed. Histological analysis demonstrated an ACTH-producing pituitary adenoma adjacent to respiratory mucous membrane consisting of ciliated epithelium with submucous connective tissue. Postoperatively, ACTH concentrations were decreased and intermittent hydrocortisone substitution treatment was initiated. At the 3-month follow up, Cushing's stigmata were found to be alleviated and the hydrocortisone dosage could be reduced. CONCLUSION: Ectopic pituitary adenoma tissue causing Cushing's disease is extremely rare but a potential cause for surgical failure or re-evaluation.

[Diabetic nephropathy: current diagnostics and treatment]. / Diabetische Nephropathie: Aktuelle Diagnostik und Therapie.

Diabetic kidney disease is a leading cause of renal failure in Germany. Albuminuria is an early diagnostic indicator of renal damage in diabetes and, aside from renal failure, a major risk factor of cardiovascular disease. An early diagnosis of diabetic kidney disease is of great importance to reduce associated cardiovascular mortality; glycemic control should aim for HbA1c levels of < 7 %. Guidelines on blood pressure differ, but it should generally be reduced to < 140/90 mmHg; stricter limits should be applied if albuminuria is present. ACE inhibitors (ACE-I) or angiotensin receptor blockers (ARB) should be preferred for blood pressure control. A combination of ACE-Is and ARBs or a renin-inhibitor therapy does not improve cardiovascular outcome, instead it increases the rate of adverse events, e.g., hyperkalemia or renal failure. Lipid control, usually with statins, should be started at an early phase of renal failure. Vitamin D receptor activation and uric acid reduction might play a future role in the treatment of diabetic kidney disease. Pharmacological modification of inflammatory signaling appears to be promising but is not yet of clinical relevance.

[Obesity and cancer]. / Adipositas und Krebs.

The incidence of obesity in the western world has increased dramatically during recent decades. Epidemiological data suggest that obesity is associated with an increased risk of several but not all types of cancers, with clear sex-specific differences. The underlying mechanisms are still a matter of debate. This review focuses on the potential factors linking obesity to cancer. Current experimental evidence suggests that insulin resistance and a chronic, subclinical inflammation in the visceral fat are the major metabolic events causing alterations in the levels of insulin, glucose, free fatty acids, insulin-like growth factor 1 (IGF-1) and 2, adipose tissue-derived proinflammatory cytokines and other bioactive molecules, such as adipokines (e.g. leptin and adiponectin), vascular endothelial growth factor (VEGF), sex hormones, gut microbiota and secondary bile acids. All these factors may act directly or indirectly on the tumor microenvironment to drive tumor progression via stimulation of cell survival/antiapoptosis, cell proliferation, angiogenesis and invasion/metastasis of the cancer cells. Therapeutic strategies that target dysfunctional or inflamed fat and have been shown to benefit patients include bariatric surgery, while other cell or hormone-directed interventions, such as conversion of visceral fat macrophages to an anti-inflammatory M2 phenotype or the pharmacological modulation of serum adipokine levels are still theoretical and need to be clinically evaluated for their ability to successfully treat or prevent obesity-related cancers.

Role of γ-aminobutyric acid signalling in the attenuation of counter-regulatory hormonal responses after antecedent hypoglycaemia in healthy men.

The attenuated counter-regulatory response to hypoglycaemia after antecedent hypoglycaemic episodes has been observed in animals to be associated with an increase in γ-aminobutyric acid (GABA) signalling. We therefore tested the hypothesis that the pharmacological suppression of GABAergic activity during a repeated hypoglycaemic episode enhances counter-regulatory responses. Fourteen healthy men participated in two experimental sessions each comprising three insulin-induced hypoglycaemic episodes. Before the third hypoglycaemic episode, participants received the GABA-antagonistic drug modafinil (200 mg orally) and placebo, respectively. In the placebo condition, the secretion of norepinephrine, adrenocorticotropic hormone, cortisol and growth hormone, and the perception of neuroglycopenic symptoms were attenuated during the third as compared with the first hypoglycaemic episode (each p < 0.05). Modafinil reversed this effect for the noradrenergic response (p < 0.05), while not significantly altering the attenuation of other hormonal responses and symptom perception (p > 0.3). Our findings indicate that increased GABAergic transmission could contribute to aspects of the attenuated counter-regulatory response after recurrent hypoglycaemia in humans.

[Diagnostics and therapy for neuroendocrine neoplasia of an unknown primary - a plea for open exploration]. / Diagnostik und Therapie bei neuroendokrinen Neoplasien mit unklarem Primarius - ein Plädoyer für die offene Exploration.

BACKGROUND: Neuroendocrine neoplasia (NEN) are a rare and heterogenous tumour entity. The subgroup with unknown primary tumour (N-CUP) seems to have a worse prognosis as resection of the primary is necessary for cure. The diagnostics and therapeutic algorithms for N-CUP in a German single centre are presented. PATIENTS/METHODS: Analysis of the surgical databank showed 35 cases of N-CUP in 261 cases with NEN from gastroenteropancreatic and lung origin over 2 decades (03/1990-03/2011). Three groups were built: K1 - primary detection after operative exploration (n = 10), K2 - unknown primary after operative exploration (n = 10) and K3 - no operative exploration for various reasons (n = 13). RESULTS: Initially 13.4 % (35/261) of patients presented as N-CUP, after intensified diagnostics 12.7 % (33/261) and after operative exploration 8.8 % (23/261) remained with unknown primary tumour. The sex ratio was 1 : 1, the median age is significantly higher in N-CUP [63.8 years (y) vs. 55.9 y, p = 0.004), the 5-year-survival is lower (58 vs. 72 %, n. s.). compared to NEN with known primary. Operative exploration was performed in 60.6 % (20/33), 30 % (6/20) of them were found to have inoperable situations, in 20 % (4/20) single site metastases were removed completely and in 50 % (10/20) a primary tumour was detected (8 × midgut, 2 × pancreas) intraoperatively. In these cases 70 % (7/10) got complete tumour resection (R0) and in 30 % (3/10) primary tumour resection with debulking of liver metastasis was done. In K3 (39.4 %, 13/33) most patients [69.2 % (9/13)] were treated with chemotherapy. The median age in K1 was significantly lower than in K3 (54.9 y vs. 68.3 y, p = 0.028), male dominance was seen in K3 (3,3 : 1, n. s.). The average Ki-67 index was 4.3, 23.8 and 53 % in K1, K2 and K3 (p < 0.0001 for K1 and K3 and p = 0.035 for K2 and K3), respectively. The death rate was 20, 30 and 76.9 % in K1, K2 and K3, respectively. CONCLUSION: Primary tumours of the midgut and pancreas are often found in the subset of well differentiated neuroendocrine CUP syndrome after open surgical exploration. A high rate of complete tumour resection and cure can be achieved in these cases. After common diagnostic tools (CT, MRI and somatostatin receptor scintigraphy), immunhistochemistry can give important hints (CDX-2 for midgut, TTF-1 for lung and thyroid) for a primary lesion. Also in single site metastasis without primary tumour detection a good clinical outcome is seen after complete resection.

[Neuroendocrine tumours of the GI tract--data from the German NET Registry]. / Neuroendokrine Tumoren des Verdauungstrakts - Daten des deutschen NET-Registers.

BACKGROUND: Neuroendocrine tumours (NET) are rare and heterogeneous neoplasia. To obtain valid data on epidemiology, diagnostics, therapy, prognosis and risk factors is the aim of the German NET registry. PATIENTS AND METHODS: Data from 2009 histologically proven NET were collected from 35 NET centres between 1999 and 2010. Data collection has been performed prospectively since 2004. Results: Median follow-up was 34.5 months and median age at diagnosis 56.4 years. Primary tumour localisations were pancreas (34.2%), midgut (5.8%), stomach (6.5%), bowel (6.9%), duodenum (4.8%) and neuroendocrine CUP (12.6%). Synchronous metastases were seen in 46% and second malignancies in 12%. From 860 patients, 402 (46.7%) had functional tumours with the following hormone excess syndromes: carcinoid syndrome (19.1%; n = 164), persistent hyperinsulinaemic hypoglycaemia (17.7%; n = 152), Zollinger- Ellison syndrome (7.1%; n = 61), glucagonoma (0.7%; n = 15), Verner-Morrison syndrome (0.4%; n = 8) and somatostatinoma syndrome(0.1%; n = 2). Surgical therapy was performed in 78%, therapy with somatostatin receptor analogues(SSA) in 28%, peptide radioreceptor therapy (PRRT) in 19%, chemotherapy in 18% and interferon therapy in 6.5%. Only surgery was done in 47%, whereas 53% received a second therapy. General mortality rate during follow-up was 14.9%. The tumour-specific survival rates for 2, 5 and 10 years were 94, 85 and 70%. The 5-year survival is dependent on the surgical or non-surgical therapy (82 versus 61%, p < 0.001) and also on the primary tumour site (90/30% for midgut, 85/65% for pancreas, p < 0.001). Grading (G1, G2, G3) based on proliferation index Ki-67 recommended by the ENETS guidelines and WHO classification is highly correlated to the 5-year survival rate (88, 82, 33%, p < 0.001). CONCLUSION: The German NET registry provides valid multicentric data on NET in Germany. Surgical therapy is the most frequent and important therapy with good clinical outcome. In non-resectable, metastatic tumours, systemic therapies are common. Continuation and evaluation of the new WHO and TNM classifications for NET and their therapies will be a future focus of the registry.