Frank Weber

University Hospital Essen | UK Essen · Surgical Clinic (Outpatient and Inpatient)

Advances in morphologic and molecular tumor characterization, tumor epidemiology and clinical outcome research have allowed for a more balanced view on the risk-benefit profile of thyroid cancer surgery [1]. The concept of personalized thyroid surgery, prompted by the advent of less invasive surgical techniques, rises to the challenge posed by the...

Purpose: Restoration of iodine incorporation (redifferentiation) by mitogen-activated protein kinase (MAPK) inhibition was achieved in previously radioiodine-refractory, unresectable thyroid carcinoma (RR-TC). However, results were unsatisfactory in BRAFV600E-mutant RR-TC. Here we assess safety and efficacy of redifferentiation therapy through gen...

Purpose The objective of this study was to provide RET genotype-specific data on recurrent ipsilateral pheochromocytoma in multiple endocrine neoplasia type 2A (MEN2A), which are sparse. Methods Kaplan-Meier analyses were performed to determine the risk of recurrent ipsilateral adrenalectomy after subtotal and total adrenalectomy in 221 carriers o...

Objective: In clinical practice, false positive results in biochemical testing for suspected pheochromocytoma/paraganglioma (PPGL) are not infrequent and may lead to unnecessary examinations. We aimed to evaluate the role of clonidine suppression test (CST) in the era of analyses of plasma free metanephrines for the diagnosis or exclusion of PPGL...

Objective This investigation aimed to delineate the age-dependent clinical penetrance and expression of heterozygous RET (REarranged during Transfection) missense mutations associated with multiple endocrine neoplasia 2A (MEN2A) according to parental inheritance. Design This was an observational study of RET carriers operated for MEN2A-associated t...

As neuroendocrine tumors are a heterogenous group of malignancies therapies have to be just as broad. This chapter describes the ranges of therapeutic options in such a rare disease taking into account current guidelines. Even in metastatic disease there are possibilities to perform surgery to increase the quality of life. The most important system...

In the past decade, the use of intraoperative neural monitoring (IONM) in thyroid and parathyroid surgery has been widely accepted by surgeons as a useful technology for improving laryngeal nerve identification and voice outcomes, facilitating neurophysiological research, educating and training surgeons, and reducing surgical complications and malp...

This study of 542 patients with follicular thyroid cancer, 366 patients with the follicular variant and 1452 patients with the classical variant of papillary thyroid cancer, and 819 patients with sporadic medullary thyroid cancer operated at a tertiary referral center aimed to determine risk patterns of distant metastasis for each tumor entity, whi...

Background: The period after parathyroidectomy (PTx) in dialysis patients is characterized by periods of severe hypocalcemia. This study aims to investigate the effect of high doses of active vitamin D immediately after PTx on the development of hypocalcemia. Materials and methods: We retrospectively reviewed 111 patients with secondary hyperpar...

Due to high morbidity and mortality of untreated hypercortisolism, a prompt diagnosis is essential. Measurement of late-night salivary cortisol provides a simple and non-invasive method. However, thresholds and reference ranges differ among studies. The goal of this study was to define a threshold of late-night salivary cortisol for the diagnosis o...

There are no data on the impact of parent-of-origin effects on the expression of multiple endocrine neoplasia type 2A (MEN2A). The present study aimed to explore effects of parent-of-origin and offspring gender in MEN2A. In total, 224 carriers harbored heterozygous RET (REarranged during Transfection) p.Cys634 missense variants, for 169 of whom inf...

123/131I-MIBG scintigraphy has shown a high specificity for imaging pheochromocytoma and paraganglioma however with low sensitivity due to low spatial resolution. 124I-MIBG PET may overcome this limitation to improve the staging of patients with (suspected) pheochromocytoma. Methods: We analyzed the sensitivity, specificity, positive and negative p...

The association of Hashimoto thyroiditis and Graves’ disease with papillary, follicular, and medullary thyroid cancer has not been comprehensively investigated until now. This comparative clinicopathological study of consecutive patients thyroidectomized at a surgical referral center aimed to explore interdependencies between chronic autoimmune thy...

The metastatic risk profile of microscopic lymphatic and venous invasion in medullary thyroid cancer is ill-defined. This evidence gap calls for evaluation of the suitability of microscopic lymphatic and venous invasion at thyroidectomy for prediction of lymph node and distant metastases in medullary thyroid cancer. In this study of 484 patients wi...

Background The tyrosine kinase inhibitors (TKI) vandetanib and cabozantinib are approved as targeted therapies in advanced medullary thyroid carcinoma (MTC) with symptoms or high tumour burden. Only recently, toxicity in long-time TKI usage was analysed. However, little is known about the impact of TKI discontinuation on MTC disease course after lo...

Aims In contrast to all prior AJCC/TNM classifications for differentiated thyroid cancer (DTC) the 8th edition does not take minimal extrathyroidal extension (M-ETE) into consideration for local tumor staging. We therefore aimed to retrospectively assess the specific impact of M-ETE on the outcome of M-ETE patients treated in our clinic. Methods D...

Intraoperative neural monitoring (IONM) is now an integral aspect of thyroid surgery in many centers. Interest in IONM and the number of institutions that perform monitored thyroidectomies have increased throughout the world in recent years. For surgeons considering the introduction of IONM in their practice, specific training in IONM devices and p...

Background and aimsThe 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...

Background: The clinical phenotype of poorly differentiated thyroid cancer (PDTC) can vary substantially. We aim to evaluate risk factors for radioiodine refractory (RAI-R) disease and reduced overall survival (OS). Methods: We retrospectively screened our institutional database for PDTC patients. For the assessment of RAI-R disease, we included...

Context Risk factors of lymph node and distant metastases have rarely been analyzed in hereditary and sporadic medullary thyroid cancer (MTC) using large genetic-clinical data sets. Objective This comprehensive investigation aimed to explore risk factors of lymph node and distant metastases and interdependencies between age at thyroidectomy, prima...

Medullary thyroid carcinomas (MTC) are rare and aggressive neuroendocrine tumors of the thyroid. About 70% of MTC are sporadic; approximately 50% of those harbour somatic RET mutation. DLL3 is widely expressed in many neuroendocrine tumors and has been evaluated as a potential therapeutic target. Since stromal desmoplasia in sporadic MTC has been i...

There is no evidence-based guidance on the extent of prophylactic neck surgery for second-generation multiple endocrine neoplasia type 2B (MEN 2B), a newly emerging entity in the molecular era. In this investigation of MEN 2B children who inherited the M918T RET germline mutation from a phenotypically affected MEN 2B parent, 6 MEN 2B children (4 gi...

Although the onset of hereditary medullary thyroid cancer (MTC) depends on mutational risk, the impact of that risk on lymph node metastasis is unclear. Included in this investigation were 387 carriers of RET germline mutations with node-negative MTC (201 carriers) or node-positive MTC (186 carriers). Age at thyroidectomy increased significantly fr...

As there are no reliable preoperative or intraoperative markers to identify follicular thyroid cancer (FTC), the postoperative histopathological diagnosis frequently raises the question of completion surgery. The oncological necessity must not be questioned by an allegedly increased morbidity. The operation is particularly indicated if there is evi...

PurposeTo determine whether published disease penetrance estimates of 50% for pheochromocytoma and 20–30% for primary hyperparathyroidism in multiple endocrine neoplasia (MEN 2A), conceivably reflecting overrepresentation of index patients with completely developed MEN 2A, may be too high.Methods Cross-sectional study of carriers at high risk of ME...

Background Neuroendocrine neoplasia (NEN) are rare and heterogenous tumours. Few data exist on the impact of surgical therapy.Materials and methodsThis is a retrospective analysis of prospectively collected data of gastroenteropancreatic NEN in the German NET-Registry (1999–2012). It focuses on patients without distant metastases (limited disease,...

Die Phäochromozytomatose ist eine multifokale, auf den operativ eröffneten Raum beschränkte Zellaussaat ohne Fernmetastasierung. Nach primärer Adrenalektomie wegen eines Phäochromozytoms stellt sie eine seltene und kaum beachtete Manifestation eines Tumorrezidivs dar. In einem Zeitraum von 2010 bis 2019 wurden in unserem Zentrum 5 Patienten mit dem...

Neuroendocrine tumours of the small intestine (SINET) are a rare disease. However, a rising incidence rate and excellent long-term survival, even in the setting of metastatic disease lead to a high prevalence of SINET of up to 11/100.000. At the time of diagnosis, most patients already suffer from metastatic disease. About one third of patients dem...

Zusammenfassung Neuroendokrine Neoplasien (NEN) umfassen eine seltene Tumorentität mit heterogener Biologie, Prognose und therapeutischen Optionen. In Zusammenhang mit der kürzlichen Publikation der ersten deutschen Leitlinie zur Diagnostik und Therapie von NEN erfolgte die Analyse der Kohorte des Deutschen NET-Registers der Deutschen Gesellschaft...

Background Because adrenal angiomyelolipoma (AAML) is rare and uniformly benign, the indications for surgery are ill defined. Methods Among a series of 156 patients with adrenal pathologies surgically treated between 2013 and 2018, 12 patients were operated with the diagnosis of an AAML. The clinical as well as imaging parameters forming the indiv...

Neuroendokrine Neoplasien (NEN) umfassen eine seltene Tumorentität mit heterogener Biologie, Prognose und therapeutischen Optionen. In Zusammenhang mit der kürzlichen Publikation der ersten deutschen Leitlinie zur Diagnostik und Therapie von NEN erfolgte die Analyse der Kohorte des Deutschen NET-Registers der Deutschen Gesellschaft für Endokrinolog...

Although already 25 years into the genomic era, age‐related progression of hereditary medullary thyroid cancer (MTC), the prevalence of which is estimated at 1 in 80,000 inhabitants, remains to be delineated for most unique RET (REarranged during Transfection) mutations. Included in this study were 567 RET carriers. The age‐related progression of M...

Background: There are few data on intermittent and continuous intraoperative nerve monitoring (IONM) during thyroidectomy in children. Methods: All children aged 18 years or younger who had standard thyroid operations using intermittent or continuous IONM between January 1998 and December 2016 were included in the study. The impact of age and ty...

Neuroendokrine Tumoren des Dünndarms sind mit einer Inzidenz von unter 1 pro 100.000 Einwohner eine eher seltene Erkrankung. Die neuroendokrinen Tumoren des Dünndarms zählen jedoch mit einem Anteil von über 20 % aller neuroendokrinen Tumoren zu den häufigsten Malignomen des Dünndarms. Aufgrund der eher unspezifischen klinischen Beschwerden erfolgt...

There is evidence in the literature that some RET (REarranged during Transfection) variants commonly associated with multiple endocrine neoplasia type 2A (MEN2A) may be more frequent in certain European countries: p.L790F in Germany; p.Y791F in Poland; and p.V804 in France and Italy. This investigation of 189 German medullary thyroid cancer familie...

Anaplastic thyroid carcinoma (ATC) is an orphan disease and in most patients fatal. So far no established treatment is available that prolongs survival. Several large retrospective studies have identified negative prognostic markers, analyzed efficacy of multimodal approaches such as radiotherapy with and without concurrent chemotherapy and chemoth...

Hepatocellular carcinoma is a cancer with increasing incidence and largely refractory to current anticancer drugs. Since Sorafenib, a multikinase inhibitor has shown modest efficacy in advanced hepatocellular carcinoma additional treatments are highly needed. Protein phosphorylation via kinases is an important post-translational modification to reg...

The majority of poorly differentiated hepatocellular carcinomas (HCCs) develop from well-differentiated tumors. Endocytosis is a cellular function which is likely to take part in this development due to its important role in regulating the abundances of vital signaling receptors. Here, we aimed to investigate the abundance of endocytosis-associated...

Context and objective: Human hepatocellular carcinoma (HCC) is a severe malignant disease, and accurate and reliable diagnostic markers are still needed. This study was aimed for the discovery of novel marker candidates by quantitative proteomics. Methods and results: Proteomic differences between HCC and nontumorous liver tissue were studied by...

The interferon-stimulated gene 15 (ISG15) plays an important role in the pathogenesis of hepatitis C virus (HCV) infection. ISG15-regulated proteins have previously been identified that putatively affect this proviral interaction. The present observational study aimed to elucidate the relation between ISG15 and these host factors during HCV infecti...

Aims: The distinction between intrahepatic cholangiocarcinoma (ICC) and benign bile duct lesions can be challenging. Using our previously identified potential biomarkers for ICC, we examined whether these are useful for the differential diagnosis of ICC, bile duct adenoma and reactive bile duct proliferations in an immunohistochemical approach and...

Hepatocellular carcinoma (HCC) is one of the most aggressive tumors and the treatment outcome of this disease is improved when the cancer is diagnosed at an early stage. This requires biomarkers allowing for an accurate and early tumor diagnosis. To identify potential markers with such applications, we analyzed a patient cohort consisting of 50 pat...

The exact discrimination of lesions with true hepatocellular differentiation from secondary tumours and neoplasms with hepatocellular histomorphology like hepatoid adenocarcinomas (HAC) is crucial. Therefore, we aimed to identify ancillary protein-biomarkers by using complementary proteomic techniques (2D-DIGE, label-free MS). The identified candid...

Hepatic fibrosis and cirrhosis are major health problems worldwide. Up to now, highly invasive biopsy remains the diagnostic gold standard despite many disadvantages. In order to develop non-invasive diagnostic assays for the assessment of liver fibrosis it is urgently necessary to identify molecules which are robustly expressed in association with...

Undifferentiated (anaplastic) thyroid carcinoma (UTC) is a very rare and aggressive disease with a median survival of about 6 months. There is no evidence-based therapy leading to improved overall survival. UTC treatment requires close interdisciplinary cooperation and is often highly variable depending on site-specific preferences. The aim of our...

Thyroid carcinoma is a rare and heterogeneous disease. Initial therapy and follow-up has to be adjusted to the individual risk for an excellent vs. poor prognosis. Differentiated thyroid cancer has a very high cure rate and is treated by surgery, usually followed by radioiodine ablation. Depending on the response to initial therapy the risk for per...

BACKGROUND & PURPOSE: Hepatocellular carcinoma (HCC) is a major lethal cancer worldwide. Despite sophisticated diagnostic algorithms, the differential diagnosis of small liver nodules still is difficult. While imaging techniques have advanced, adjuvant protein-biomarkers as glypican3 (GPC3), glutamine-synthetase (GS) and heat-shock protein 70 (HSP...

Das hepatozellulare Karzinom (HCC) ist einer der haufigsten malignen Tumore weltweit und ist durch eine eingeschrankte therapeutische Zuganglichkeit und somit schlechte Prognose charakterisiert. Die Entstehungsmechanismen des molekular sehr heterogenen Tumors sind bislang unzureichend verstanden. Um die Bedeutung des TNF-related apoptosis indicing...

The proapoptotic molecule TNF-related apoptosis-inducing ligand (TRAIL) has earned attention because of its ability to induce apoptosis in liver cancer cells without damaging normal liver cells. It may play an important role in preventing the development and outgrowth of hepatocellular carcinoma (HCC). TRAIL expression was investigated in a large s...

The aim of this study was the identification of novel biomarker candidates for the diagnosis of cholangiocellular carcinoma (CCC) and its immunohistochemical differentiation from benign liver and bile duct cells. CCC is a primary cancer which arises from the epithelial cells of bile ducts and is characterised by high mortality rates due to its late...

Background: Local ablative techniques such as selective internal radiation therapy (SIRT) have become the mainstay of treating hepatocellular carcinoma (HCC) in the bridging-to-transplant and palliative setting. We recently demonstrated that epithelial circulating tumor cells (CTCs) correlate to an unfavorable outcome. We wanted to scrutinize whet...

Immune responses by innate and adaptive immune cells are crucial for the suppression of carcinogenesis and tumor spread. Cytotoxic CD8+ T (CTL), natural killer (NK) and natural killer T cells (NKT) prevent tumor growth by their ability to induce apoptosis in cancer cells. To circumvent anti-tumor immunity, tumors commonly attract regulatory T (Treg...

Aims: Hepatocellular carcinoma (HCC) is characterised by a very poor prognosis and is associated with high mortality. This accounts for the molecular mechanisms of development of this tumor, which are herterogenous and only incompletely understood. We could previously show that the promyelocytic leukaemia (PML) protein, a nuclear phosphoprotein whi...