[Gastroenteropancreatic neuroendocrine neoplasms-Surgery in a multimodal concept]. / Gastroenteropankreatische neuroendokrine Neoplasien ­ Chirurgie im multimodalen Konzept.

Gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) are mainly found in the small intestine and pancreas. The course of the disease in patients is highly variable and depends on the degree of differentiation (G1-G3) of the neoplasm. The potential for metastasis formation of GEP-NEN is high even with good differentiation (G1). Lymph node metastases and, in many cases, liver metastases are also often found. Less common are bone metastases or peritoneal carcinomas. The treatment of these GEP-NENs is surgical, whenever possible. If an R0 resection with removal of all lymph node and liver metastases is successful, the prognosis of the patients is excellent. Patients with diffuse liver or bone metastases can no longer be cured by surgery alone. The long-term survival of these patients is nowadays possible due to the availability of drugs (e.g., somatostatin analogues, tyrosine kinase inhibitors), peptide receptor radionuclide therapy (PRRT) and liver-directed procedures, with a good quality of life.

Mutation-based, short-term "neoadjuvant" treatment allows resectability in stage IVB and C anaplastic thyroid cancer.

INTRODUCTION: Few available data indicate that a mutation-based "neoadjuvant" therapy in advanced anaplastic thyroid carcinoma (ATC) might convert an initially unresectable primary tumor to resectable and optimize local tumor control. We evaluated a preoperative short-term "neoadjuvant" therapy with a BRAF-directed therapy or, in case of BRAF non-mutated tumors, an mKI/checkpoint inhibitor combination in three patients with ATC stage IVB and C. METHODS: In the context of preoperative diagnostics, immunohistochemistry (IHC) assessment and genetic analysis was started as soon as possible. The antiangiogenetic therapy with lenvatinib was immediately after diagnosis of ATC started as bridging therapy. In case of a BRAF-mutated ATC, a combination therapy of dabrafenib and trametinib, in case of BRAF-wildtype ATC a combination of pembrolizumab and lenvatinib was given for 4 weeks. If re-staging has shown a significant therapy response due to a decrease in size of > 50%, surgical resection was reconsidered. A primary tumor resection was performed first. As a second step, limited distant metastasis have been resected approximately 4 weeks after thyroid surgery. After postoperative recovery, the targeted systemic therapy was continued. PATIENTS: Two patients presented with BRAF-wildtype ATC stage IVC, one with BRAF-mutated ATC stage IVB. All patients were evaluated by surgery, nuclear medicine and oncology upon diagnosis of ATC. RESULTS: In all three cases, the "neoadjuvant" therapy induced a dramatic response and led to local resectability in primarily non-resectable ATC stage IVB or C. We have chosen for the first time a short-term "neoadjuvant" treatment period to reduce the risk of bleeding and/or fistula due to potential rapid tumor shrinkage. The results of surgery after only short-term "neoadjuvant" therapy showed two R0 und one R1 resections. Postoperative histopathological findings confirmed an extent of tumor necrosis or regressive fibrotic tissue between 60 and > 95% in our patients. CONCLUSIONS: A short-term mutation-based "neoadjuvant" therapy can achieve local resectability in initially unresectable ATC stage IVB or C. A neoadjuvant treatment period of about 4 weeks seems to show similar response as a treatment duration of at least 3 months.

[Are there still indications for open adrenalectomy?] / Gibt es noch Indikationen für die offene Adrenalektomie?

Despite the triumph of minimally invasive techniques in adrenal surgery, the indications for open adrenalectomy are indispensable in the canon of treatment options and must remain part of the repertoire of visceral surgery. Open adrenalectomy is indicated for advanced adrenal carcinoma (ENSAT stage III). In addition to the frequent local infiltration of these carcinomas which makes the en bloc resection of adjacent organs necessary, thromboses in the renal vein or the vena cava or multiple lymph node metastases can also necessitate an open procedure; however, open adrenalectomy is justified and must also be discussed for adrenocortical carcinoma ENSAT stages I-II (tumor size ≤ 5 cm or > 5 cm, NO). Furthermore, highly suspicious large adrenal tumors (6-8 cm, Hounsfield units > 20) without preoperative evidence of malignancy and other adrenal pathologies, such as neuroblastomas, large pheochromocytomas and also schwannomas can be an indication for open adrenalectomy.

Management of primary and renal hyperparathyroidism: guidelines from the German Association of Endocrine Surgeons (CAEK).

BACKGROUND AND AIMS: The purpose of this review is to provide updated recommendations for the surgical management of primary (pHPT) and renal (rHPT) hyperparathyroidism, formulating a new guideline of the German Association of Endocrine Surgeons (CAEK). METHODS: Evidence-based recommendations for the diagnosis and therapy of pHPT and rHPT were assessed by a multidisciplinary panel using PubMed for a comprehensive literature search together with a structured consensus dialogue (S2k guideline of the Association of the German Scientific Medical Societies, AWMF). RESULTS: During the last 20 years, a variety of new preoperative localization procedures, such as sestamibi-SPECT, 4D-CT, and various PET/CT procedures, were established for pHPT. High-resolution imaging, together with intraoperative parathyroid hormone (IOPTH) measurement, enabled focused or minimally invasive surgery to become the most favored surgical technique. Patients with pHPT and nonlocalizing imaging have a higher risk of multiglandular disease. Surgical therapy provides very high cure rates, with a clear relation to the surgeon's experience in parathyroid procedures. Reoperative parathyroidectomy, children with pHPT or familial forms, and parathyroid carcinoma are addressed and require special surgical expertise. A multidisciplinary team of experienced nephrologists, transplant, and endocrine surgeons should assess the diagnosis and treatment of renal HPT. CONCLUSION: Surgery is the only curative treatment for pHPT and should be considered for all patients with pHPT. For rHPT, a more selective approach is required, and parathyroidectomy is indicated only when conservative treatment options fail. In parathyroid carcinoma, the adequacy of local resection influences local disease control.

Hmong participants' reactions to return of individual and community pharmacogenetic research results: "A positive light for our community".

Pharmacogenetic research has historically lacked racial and ethnic diversity, limiting the application of findings to minority populations. Recent studies, including the Hmong, have gauged communities' interest in participating in genomic research and receiving their individual results. This study was conducted to create a culturally and linguistically appropriate format to return pharmacogenomic results and identify Minnesota Hmong research participants' reactions to their personal and collective results. Using a community-based participatory research approach, researchers collaborated with Hmong community members to format the pharmacogenetic disclosure process. Three focus groups were completed with 24 Hmong participants and three major themes emerged using thematic analysis. Many Hmong focus group participants viewed the results positively, finding them useful for themselves and their community as a means to optimize responses to and avoid harms from medicines. However, some participants expressed concerns about harms that the pharmacogenetic information could bring, including anxiety, misunderstanding, discrimination, exploitation, and lack of a clinician involvement in interpreting and applying the result. Many participants interpreted their results through an experiential lens, trusting their experience of medicines more than trusting genetic information, and through a cultural lens, expressing the belief that environmental factors may influence how people's bodies respond to medicines by influencing their inherited flesh and blood (roj ntsha). Lastly, participants stressed the importance of disseminating the information while acknowledging the complex linguistic, educational, and cultural factors that limit understanding of the results. Researchers, genetic counselors, pharmacists, and healthcare providers should strive to return results in meaningful ways to all members of society.

[Nodular goiter]. / Struma nodosa.

The indications for surgery of benign goiter should be balanced and professional as the prevalence of benign nodular goiter in Germany is high and not all goiters must be surgically treated. Thyroid nodules are detected in up to 76% of healthy people using modern high-resolution ultrasound (US) and only a few of these nodules are malignant or symptomatic. Even today a thorough medical history, detailed examination of the neck region, a qualified US of the thyroid gland, a 99m-technetium scintigraphy and fine needle aspiration help to select patients who will benefit from thyroid surgery. In the last 10 years several thyroid imaging reporting and data systems (TI-RADS) classifications have been introduced. The TI-RADS classification is a standardized assessment of thyroid nodules and risk stratification system in thyroid US which helps to select those nodules with a high risk of cancer. Asymptomatic euthyroid nodular goiter without any suspicion of malignancy and scintigraphically cold thyroid nodules without any other evidence of malignancy are not indications for thyroid surgery. The decision to operate should be made on an interdisciplinary basis in conformity with the relevant guidelines and exhaustion of diagnostic tools.

Anaplastic thyroid carcinoma: changing trends of treatment strategies and associated overall survival.

PURPOSE: The prognosis of anaplastic thyroid cancer (ATC) is poor. Despite various attempts to modify common treatment modalities, including surgery, external beam radiation (EBRT) and chemotherapy (CTX), no standardized treatment is yet established. This study aimed to analyze the changing trends of treatment concepts and associated overall survival (OS) over the last two decades. METHODS: A retrospective analysis was conducted on 42 patients with histologically confirmed ATC. The outcome measures included the evaluation of clinical characteristics and treatments performed with regard to OS. RESULTS: Median OS for all tumor stages was 6 (range 1 week-79) months, 6.5 months for stage IVA/B and 4 months for stage IVC carcinoma patients. Twenty-one patients with stage IVA/B carcinomas underwent curative treatment, including thyroidectomy with lymphadenectomy (TTX plus LAD, n = 11) or multimodal treatment with TTX plus LAD and EBRT plus/minus CTX (n = 10). The median OS of patients with stage IVA/B carcinomas was significantly prolonged after multimodal treatment than after surgery alone (25 vs. 3 months, p = 0.04). Fifteen of 18 patients with stage IVC carcinomas received palliative, 3 patients multimodal treatment. The median OS of stage IVC patients after trimodal therapy was not significantly longer than after debulking procedures (6 vs. 7 months, p = 0.25). In the time period 1999-2009, only 4 (21%) patients received multimodal treatment compared to 9 (39%) in the period from 2009 to 2019, but this did not result in a significantly prolonged survival in the latter period (8.5 vs. 15 months, p = 0.61). CONCLUSION: Concurrent radio- and/or chemotherapy in combination with surgery seems to result in improved survival in stage IVA/B ATC, whereas this is not the case in patients with stage IVC tumors. Novel treatment regimens are urgently needed to improve the dismal prognosis of ATC.

Renal Tubular Dysgenesis in a Case of Fetus Acardius Amorphus.

Fetus acardius amorphus is a rare congenital malformation characterized by the lack of a functional heart, the presence of a bivascular umbilical cord, as well as a developed and organized skeletal system and partially organized inner organs. Fetus acardii mostly occur in multiple gestations. The pathogenesis of this entity is not clarified yet. It has been hypothesized that, although formation of anastomosing vessels between the co-twin and the anomalous embryo as well as reverse directed blood flow within the umbilical arteries of the weaker twin may allow sufficient blood flow to form rudimentary internal organs, it is insufficient to develop a fully functional heart. We had a case of fetus acardius amorphus, where we performed autopsy as well as routine histology assessment to identify different types of tissues. We showed that our fetus acardius amorphus demonstrated histomorphological features of renal tubular dysgenesis, confirmed by lack of proximal tubules, extramedullary hematopoiesis and increased number of smooth muscle actin positive vessels. This is a novel finding and has not been reported previously.

[Surgical treatment of parathyroid carcinoma : Does the initial en bloc resection improve the prognosis?] / Chirurgie des Nebenschilddrüsenkarzinoms : Verbessert die initiale En-bloc-Resektion die Prognose?

BACKGROUND: Radical en bloc resection of the tumor with ipsilateral hemithyroidectomy and central lymphadenectomy (PTX+HTX) is currently the generally recommended treatment strategy for parathyroid carcinoma (PC) in Germany; however, it remains unclear whether the en bloc resection leads to a prognostic benefit compared to parathyroidectomy (PTX) alone, especially considering disease-free and overall survival. OBJECTIVE: This study analyzed the survival of patients with PC after PTX+HTX compared to patients with PTX. METHODS: Patients with PC were identified from a prospective database and retrospectively analyzed regarding clinicopathological features, surgical treatment, disease-free interval and overall survival. RESULTS: Out of 1705 patients who were operated on because of primary hyperparathyroidism (pHPT), 18 (1.1%) had histologically confirmed PC. In nine patients PTX+HTX was initially performed and the other nine patients received only PTX. After PTX, all of the nine patients developed a recurrence after a median of 18 months (range 7-84 months), while only one patient had a recurrence after PTX+HTX. After PTX a median three (range 2-18) reoperations were indicated for relapse but after PTX+HTX only one patient had to undergo two relapse surgeries (p < 0.001). The recurrence-free survival after PTX+HTX was significantly longer than after PTX (143 vs. 18 months, p = 0.01), while the overall survival of both groups after a median follow-up of 107.5 months did not significantly differ. DISCUSSION: If there is any clinical suspicion of PC, an en bloc resection should be performed to prolong recurrence-free survival and avoid reoperations.

Surgical therapy of adrenal tumors: guidelines from the German Association of Endocrine Surgeons (CAEK).

BACKGROUND AND AIMS: Previous guidelines addressing surgery of adrenal tumors required actualization in adaption of developments in the area. The present guideline aims to provide practical and qualified recommendations on an evidence-based level reviewing the prevalent literature for the surgical therapy of adrenal tumors referring to patients of all age groups in operative medicine who require adrenal surgery. It primarily addresses general and visceral surgeons but offers information for all medical doctors related to conservative, ambulatory or inpatient care, rehabilitation, and general practice as well as pediatrics. It extends to interested patients to improve the knowledge and participation in the decision-making process regarding indications and methods of management of adrenal tumors. Furthermore, it provides effective medical options for the surgical treatment of adrenal lesions and balances positive and negative effects. Specific clinical questions addressed refer to indication, diagnostic procedures, effective therapeutic alternatives to surgery, type and extent of surgery, and postoperative management and follow-up regime. METHODS: A PubMed research using specific key words identified literature to be considered and was evaluated for evidence previous to a formal Delphi decision process that finalized consented recommendations in a multidisciplinary setting. RESULTS: Overall, 12 general and 52 specific recommendations regarding surgery for adrenal tumors were generated and complementary comments provided. CONCLUSION: Effective and balanced medical options for the surgical treatment of adrenal tumors are provided on evidence-base. Specific clinical questions regarding indication, diagnostic procedures, alternatives to and type as well as extent of surgery for adrenal tumors including postoperative management are addressed.

[Update of the S2k guidelines : Surgical treatment of benign thyroid diseases]. / Aktualisierung der S2k-Leitlinie : Operative Therapie benigner Schilddrüsenerkrankungen.

Thyroid resections represent one of the most common operations with 76,140 interventions in the year 2016 in Germany (source Destatis). These are predominantly benign thyroid gland diseases. Recommendations for the operative treatment of benign thyroid diseases were last published by the CAEK in 2010 as S2k guidelines (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e.V. [AWMF] 003/002) against the background of increasingly more radical resection procedures. Hemithyroidectomy and thyroidectomy are routinely performed for benign thyroid disease in practice. The operation-specific risks show a clear increase with the extent of the resection. Therefore, weighing-up of the risk-indications ratio between unilateral lobectomy or thyroidectomy necessitates an independent evaluation of the indications for both sides. This principle in particular has been used to update the guidelines. In addition, the previously published recommendations of the CAEK for correct execution and consequences of intraoperative neuromonitoring were included into the guidelines, which in particular serve the aim to avoid bilateral recurrent laryngeal nerve paralysis. Moreover, the recommendations for the treatment of postoperative complications, such as hypoparathyroidism and postoperative infections were revised. The updated guidelines therefore represent the current state of the science as well as the resulting surgical practice.

Inherently Radiopaque Narrow-Size-Calibrated Microspheres: Proof of Principle in a Pig Embolization Model.

PURPOSE: To investigate radiopacity, size and size calibration, morphology, and vascular distribution of inherently radiopaque microspheres in vitro and in a pig embolization model. MATERIALS AND METHODS: We compared three types of microspheres: DCBead™ (size 100-300 µm) and Embozene™ (250 µm) as clinically established microspheres, and the prototype Visible (250 µm) that contains additional radiopaque material. Size and size calibration of microspheres were examined by laser diffraction. Pulmonary artery embolization was performed in 12 pigs, and radiopacity was examined by in vitro micro-computed tomography (CT), in vivo cone-beam CT, and ex vivo micro-CT after killing. Morphology and vascular distribution of microspheres were microscopically examined. RESULTS: In in vitro and ex vivo micro-CT, radiopacity of Visible was higher than that of Embozene™, whereas DCBead™ showed no radiopacity. In in vivo cone-beam CT, radiopacity was observed with Visible but not with Embozene™ and DCBead™. Laser diffraction revealed that 7.0% (Visible), 6.5% (Embozene™), and 22.5% (DCBead™) of microspheres were smaller than 223.5 µm. Visible and Embozene™ microspheres were very often located in bronchiolus-associated arteries, but rarely in subsegmental and capillary arteries, whereas DCBead™ were very often and often detected in bronchiolus-associated arteries and capillary arteries, respectively (and rarely in subsegmental arteries). CONCLUSION: After pulmonary artery embolization, Visible but not Embozene™ or DCBead™ provide in vivo radiopacity in cone-beam CT. In contrast to non-narrow-size-calibrated DCBead™, pulmonary artery embolization with narrow-size-calibrated Visible and Embozene™ result in a predictable arterial distribution without embolization-related hemorrhagic lung infarction.

[Surgical strategies for small sporadic neuroendocrine pancreatic tumors]. / Chirurgisches Vorgehen bei kleinen sporadischen neuroendokrinen Pankreastumoren.

Small (<2 cm) sporadic neuroendocrine pancreatic neoplasms (pNENs) are a heterogeneous group of neoplasms, which can be separated into functionally active or non-functional tumors. Functionally active pNENs release various hormones, such as insulin, gastrin, glucagon and vasoactive intestinal hormones and therefore lead to severe symptoms independent of their size. The main symptoms include hypoglycemia, coma (insulinoma), diarrhea (gastrinoma, VIPoma), intestinal ulcers (gastrinoma) and hyperglycemia (glucagonoma). Asymptomatic inactive pNENs do not cause a hormonal syndrome even though in immunohistochemistry they are positive for various hormones and endocrine markers (e.g. chromogranin and synaptophysin). Non-active small pNENs are increasingly being found because of the widespread use of high-resolution imaging and are named incidental pNENs. The current therapy algorithms of small functionally active and non-functional pNENs are very different and include besides non-operative management and surveillance (wait and see strategy) of non-active pNENs (G1, low G2), all minimally invasive, open and robotic techniques of pancreas resection. Until today almost all recommendations of surgical and nonsurgical therapy algorithms have been established based on retrospective data.

Guideline Compliance in Surgery for Thyroid Nodules - A Retrospective Study.

Diagnostic guidelines for thyroid nodules focus on malignancy risk assessment to avoid unnecessary diagnostic operations. These guidelines recommend a combination of tests in form of a diagnostic algorithm. The present study analyzed the recommended algorithm and its implementation by different medical professionals. Preoperative diagnostic procedures, laboratory tests and histopathological findings of patients who underwent thyroid surgery between 2006 and 2013 were analyzed. The results were stratified by the assignation by specialized endocrinologists (ENP), general practitioners (GP) or Goethe-University Hospital Frankfurt (UKF). 677 patients were enrolled, of these 62% were assigned by UKF, 18.5% by an ENP and 19.5% by a GP. Ultrasonography rate was significantly higher in UKF (97.6%) compared to patients assigned by GP (90.9%, p<0.0001). Rates for fine-needle aspiration cytology ranged between 47.6% in UKF and 23.2% in ENP (p<0.0001). In over 93% of the patients an analysis of thyroid-stimulating hormone and triiodothyronine/thyroxin was realized. The overall malignancy rate was 11.82%. The malignancy rate was significantly higher if a FNA biopsy was performed (16.35 vs. 8.94%; p=0.0048). A higher malignancy rate could only be seen if the preoperative diagnostic workup included FNA. Besides this, the grade of algorithm adherence showed no effect on the malignancy rate.

The novel MKL target gene myoferlin modulates expansion and senescence of hepatocellular carcinoma.

Megakaryoblastic Leukemia 1 and 2 (MKL1/2) are transcriptional coactivators of Serum Response Factor (SRF) with an essential role for hepatocellular carcinoma (HCC) growth and oncogene-induced senescence. In this report, we identified myoferlin as a novel MKL/SRF target gene by gene expression profiling and verification in vivo in HCC xenografts. Myoferlin was overexpressed in human and murine HCCs triggered by conditional expression of constitutively active SRF-VP16 protein in hepatocytes. Furthermore, myoferlin was required for HCC cell invasion, proliferation and anchorage-independent cell growth. We provide evidence that myoferlin is a crucial gene target of MKL1/2 mediating its effect on oncogene-induced senescence by modulating the activation state of the EGFR and downstream MAPK and p16-/Rb pathways. Depletion of myoferlin in tumour cells from SRF-VP16-derived murine HCCs induced a senescence phenotype. These findings identify MKL1/2 and myoferlin as novel therapeutic targets to treat human HCC by a senescence-inducing strategy.

Amplicon-Based Pyrosequencing Reveals High Diversity of Protistan Parasites in Ships' Ballast Water: Implications for Biogeography and Infectious Diseases.

Ships' ballast water (BW) commonly moves macroorganisms and microorganisms across the world's oceans and along coasts; however, the majority of these microbial transfers have gone undetected. We applied high-throughput sequencing methods to identify microbial eukaryotes, specifically emphasizing the protistan parasites, in ships' BW collected from vessels calling to the Chesapeake Bay (Virginia and Maryland, USA) from European and Eastern Canadian ports. We utilized tagged-amplicon 454 pyrosequencing with two general primer sets, amplifying either the V4 or V9 domain of the small subunit (SSU) of the ribosomal RNA (rRNA) gene complex, from total DNA extracted from water samples collected from the ballast tanks of bulk cargo vessels. We detected a diverse group of protistan taxa, with some known to contain important parasites in marine systems, including Apicomplexa (unidentified apicomplexans, unidentified gregarines, Cryptosporidium spp.), Dinophyta (Blastodinium spp., Euduboscquella sp., unidentified syndinids, Karlodinium spp., Syndinium spp.), Perkinsea (Parvilucifera sp.), Opisthokonta (Ichthyosporea sp., Pseudoperkinsidae, unidentified ichthyosporeans), and Stramenopiles (Labyrinthulomycetes). Further characterization of groups with parasitic taxa, consisting of phylogenetic analyses for four taxa (Cryptosporidium spp., Parvilucifera spp., Labyrinthulomycetes, and Ichthyosporea), revealed that sequences were obtained from both known and novel lineages. This study demonstrates that high-throughput sequencing is a viable and sensitive method for detecting parasitic protists when present and transported in the ballast water of ships. These data also underscore the potential importance of human-aided dispersal in the biogeography of these microbes and emerging diseases in the world's oceans.

PATIENTS' SAFETY AND FEASIBILITY OF INTRAVENOUS URAPIDIL IN THE PRETREATMENT OF PHEOCHROMOCYTOMA PATIENTS IN A NORMAL WARD SETTING - AN ANALYSIS OF 20 CONSECUTIVE CASES.

CONTEXT: The intravenously administered selective α1 antagonist urapidil represents an alternative to phenoxybenzamine in the preoperative treatment of pheochromocytoma patients. OBJECTIVE: The aim of the study was to investigate the blood pressure changes in pheochromocytoma patients with urapidil pretreatment with special regards to the need for interventions in order to estimate the safety of this treatment in a normal ward setting. DESIGN: The medical records of all patients who underwent adrenalectomy for PCC were reviewed retrospectively. Systolic blood pressure values >180mmHg were defined as hypertensive episodes and systolic blood pressure values < 50mmHg as hypotensive episodes. Episodes of blood pressure instabilities were considered significant and recorded as intervention if they led to a direct action. RESULTS: Twenty consecutive patients who received urapidil pretreatment were enrolled in this retrospective study. Preoperatively, a median of 9 blood pressure measurements per day have been performed on the ward. A total of 2 episodes of hypertension occurred, and 1 episode of hypotension has been recorded. In the period from 25-72 hours postoperatively the median number of blood pressure measurements was 5 per 24 hours. The blood pressure deviations led to a total of 3 interventions for hypertension in 1 (5%) patients and 5 interventions for hypotension in 3 (15%) patients. All interventions could be managed on the normal ward, without the need to transfer the patient to an ICU. CONCLUSIONS: Intravenous urapidil can safely be administered on a normal ward without putting patients at risk. Intensive monitoring beyond 24 hours postoperatively was not necessary, the blood pressure measurements during the shift on a normal ward were sufficient for maintaining patients' safety.

[Gastroenteropancreatic neuroendocrine tumors : targeted diagnostics and therapy]. / Gastroenteropankreatische neuroendokrine Tumoren : Zielgerichtete Diagnostik und Therapie.

Gastroenteropancreatic neuroendocrine tumors (GEP-NET) are rare but an increase in incidence has been recognized worldwide. Approximately 70 % of NETs are localized in the gastrointestinal tract and in the pancreas, other locations are in the lungs (25 %) and rarely in the skin, urogenital tract and ovaries. Depending on the size, localization, grading (G1-G3) and production of hormones, the symptoms of patients can greatly vary. Outcome and survival of patients depend on the biological behavior and grading of the NET. Patients with a well differentiated G1 grade NET have a slow, sometimes also benign course over decades even with metastases in contrast to patients with G3 grade NETs. These tumors exhibit an aggressive behavior and patient survival is short. Liver and lymph node metastases are common (about 50 %) in GEP-NETs even at the initial diagnosis. The 5-year and 10-year survival of patients with GEP-NETs is increasing (currently approximately 80 % and 60 %, respectively), especially when a multidisciplinary team (e.g. surgery, endocrinology, oncology, nuclear medicine and gastroenterology) manages GEP-NET patients.

Vascular endothelial growth factor--marker for proliferation in thyroid diseases?

UNLABELLED: Vascular endothelial growth factor (VEGF) is a critical regulator of angiogenesis and is involved in tumor development. To date, the role of VEGF in benign diseases of the thyroid is not well known. The purpose of the present study is to determine the expression of VEGF and its receptors in primary cultures of human thyrocytes. METHODS: 50 patients with uninodular (n=11), multinodular (n=15), recurrent goiter (n=14) and Graves' disease (n=10) were enrolled. Nodular and corresponding paranodular tissue was obtained after surgery and investigated. RNA and protein were extracted from primary thyrocyte cultures. PCR, western blot and ELISA were performed to evaluate VEGF isoforms and VEGF receptor 1 and 2. RESULTS: Significantly increased transcription and protein expression of VEGF and its receptors were detected in nodular tissue of uninodular and recurrent goiter compared to the corresponding normal tissue. Active secretion of VEGF by thyrocytes was confirmed by ELISA. In multinodu-lar goiter, no difference could be found between nodular and corresponding paranodular tissue in terms of expression of VEGF or its receptors. Furthermore, we found the highest levels of VEGF and its receptors in tissue obtained from patients with Graves' disease. CONCLUSION: Increased expression of VEGF and its receptors might be crucial in the proliferation of thyrocytes and therefore may contribute to the development of goiter and goiter recurrence.