Lukaskrankenhaus Neuss

Neuß, Germany

Lukaskrankenhaus Neuss

Neuß, Germany
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Werminghaus P.,Heinrich Heine University Düsseldorf | Haase M.,Heinrich Heine University Düsseldorf | Hornsby P.J.,University of Texas Health Science Center at San Antonio | Schinner S.,Heinrich Heine University Düsseldorf | And 6 more authors.
Journal of Steroid Biochemistry and Molecular Biology | Year: 2014

Hedgehog (Hh)-signaling pathway is important in embryonic development. Activation of Hh-signaling is associated with tumorigenesis. Recent studies demonstrate that Hh-signaling is involved in the development of the adrenal gland in mice and is important in regulating adrenal proliferation. We studied the expression of Sonic hedgehog (SHH), Smoothened (SMO), Patched1 (PTCH1) and GLI family zinc finger 1 (GLI1) in human adrenal and in adrenocortical tumors using immunohistochemistry and semi-quantitative reverse transcriptase- polymerase chain reaction. Modulation of GLI1 and SMO messenger ribonucleic acid (mRNA) expression was investigated with forskolin. The role of Hh-signaling was studied in NCI-H295R cells and in an immortalized primary cell line using the Hh-agonist smoothened agonist (SAG) and the Hh-antagonist cyclopamine. The Hh-pathway components SHH, GLI1, PTCH1 and SMO were detectable in all adrenal glands. While in cortisol-producing adenomas (CPA), Hh-signaling expression levels were comparable to that in normal adrenal cortex, a much higher mRNA expression of GLI1, SMO and SHH was observed in non-producing adenomas (NPA). Interestingly, stimulation of cultured adrenal cells with forskolin led to a decrease in expression of GLI1 and SMO mRNAs. Antagonism of Hh-signaling resulted in a lower proliferation rate of adrenocortical cells, while Hh-agonism had no significant effect on adrenal cell proliferation. Our data show Hh-signaling activity in adult adrenal glands. Activation of the PKA pathway results in lower expression of Hh-signaling proteins. This might explain the lower expression of the Hh components GLI1 and SMO in CPA in comparison to the higher expression in NPA. Hh-signaling might be involved in the tumorigenesis of NPA. © 2013 Elsevier Ltd. All rights reserved.


Dralle H.,Martin Luther University of Halle Wittenberg | Musholt T.J.,Johannes Gutenberg University Mainz | Schabram J.,St. Josefs Krankenhaus Giessen | Steinmuller T.,DRK Kliniken Berlin Westend | And 22 more authors.
Langenbeck's Archives of Surgery | Year: 2013

Introduction: Over the past years, the incidence of thyroid cancer has surged not only in Germany but also in other countries of the Western hemisphere. This surge was first and foremost due to an increase of prognostically favorable ("low risk") papillary thyroid microcarcinomas, for which limited surgical procedures are often sufficient without loss of oncological benefit. These developments called for an update of the previous practice guideline to detail the surgical treatment options that are available for the various disease entities and tumor stages. Methods: The present German Association of Endocrine Surgeons practice guideline was developed on the basis of clinical evidence considering current national and international treatment recommendations through a formal expert consensus process in collaboration with the German Societies of General and Visceral Surgery, Endocrinology, Nuclear Medicine, Pathology, Radiooncology, Oncological Hematology, and a German thyroid cancer patient support organization. Results: The practice guideline for the surgical management of malignant thyroid tumors includes recommendations regarding preoperative workup; classification of locoregional nodes and terminology of surgical procedures; frequency, clinical, and histopathological features of occult and clinically apparent papillary, follicular, poorly differentiated, undifferentiated, and sporadic and hereditary medullary thyroid cancers, thyroid lymphoma and thyroid metastases from primaries outside the thyroid gland; extent of thyroidectomy; extent of lymph node dissection; aerodigestive tract resection; postoperative follow-up and surgery for recurrence and distant metastases. Conclusion: These evidence-based recommendations for surgical therapy reflect various "treatment corridors" that are best discussed within multidisciplinary teams and the patient considering tumor type, stage, progression, and inherent surgical risk. © 2013 Springer-Verlag Berlin Heidelberg.


Wirowski D.,Lukaskrankenhaus Neuss | Goretzki P.E.,Lukaskrankenhaus Neuss | Schwarz K.,Lukaskrankenhaus Neuss | Lammers B.J.,Lukaskrankenhaus Neuss | And 2 more authors.
Experimental and Clinical Endocrinology and Diabetes | Year: 2013

Introduction: Advanced preoperative imaging of parathyroid adenomas and intraoperative parathyroid hormone determination optimized the results in the surgical treatment of primary hyperparathyroidism patients. We asked, whether reasons for failure have changed during the last 25 years. Materials and methods: We retrospectively analyzed operations for persistent primary hyperparathyroidism in our department between 2001 and 2011 (n=67), and compared these results to our experience between 1986 and 2001 (n=80). Results: From 2001 to 2011, 765 primary hyperparathyroidism patients were operated on at our department. All but 4 patients were cured (761/765, 99.5%). 67 operations were performed for persistent primary hyperparathyroidism. Main reasons for failure were a misdiagnosed sporadic multiple gland disease in our own patients (18/29, 62.1%), and an undetected solitary adenoma in patients referred to us after initial operation in another hospital (22/38, 57.9%) (statistically significant). From 1986 to 2001 (1 105 primary hyperparathyroidism patients), main indications for re-operation due to persistent disease were an undiagnosed sporadic multiple gland disease in our own patients (15/24, 62.5%), and a missed solitary adenoma in patients being operated on primarily somewhere else (38/56, 67.9%) (statistically significant). Conclusions: Comparing our experience in 147 patients with persistent primary hyperparathyroidism being operated on between 2001-2011 and 1986-2001, not much has changed with the modern armamentarium of improved preoperative imaging or intraoperative biochemical control. Whereas sporadic multiple gland disease was the most common reason for unsuccessful surgery in experienced hands, other units mainly failed due to an undetected solitary adenoma. Re-operations for persistent primary hyperparathyroidism performed by us were successful in 93.8% (2001-2011) and 96.0% (1986-2001), respectively. © J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart . New York.


PubMed | MVZ Gesundheitszentrum St. Marien GmbH, Studienzentrum Onkologie Ravensburg, ClinAssess GmbH, Universitatsmedizin Greifswald and 14 more.
Type: Journal Article | Journal: The Lancet. Oncology | Year: 2016

FIRE-3 compared first-line 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) plus cetuximab with FOLFIRI plus bevacizumab in patients with KRAS exon 2 wild-type metastatic colorectal cancer. The same study also reported an exploratory analysis of a subgroup of patients with tumours that were wild-type at other RAS genes (KRAS and NRAS exons 2-4). We report here efficacy results for the FIRE-3 final RAS (KRAS/NRAS, exons 2-4) wild-type subgroup. Moreover, new metrics of tumour dynamics were explored during a centralised radiological review to investigate how FOLFIRI plus cetuximab conferred overall survival benefit in the absence of differences in investigator-assessed objective responses and progression-free survival.FIRE-3 was a randomised phase 3 trial comparing FOLFIRI plus cetuximab with FOLFIRI plus bevacizumab in the first-line treatment of patients with KRAS exon 2 wild-type metastatic colorectal cancer. The primary endpoint of the FIRE-3 study was the proportion of patients achieving an objective response according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.0 in the intention-to-treat population. A centralised radiological review of CT scans was done in a post-hoc analysis to assess objective response according to RECIST 1.1, early tumour shrinkage, depth of response, duration of response, and time to response in the final RAS wild-type subgroup. Comparisons between treatment groups with respect to objective response rate and early tumour shrinkage were made using Fishers exact test (two-sided), while differences in depth of response were investigated with a two-sided Wilcoxon test. This trial is registered at ClinicalTrials.gov, number NCT00433927.In the final RAS wild-type population (n=400), median overall survival was better in the FOLFIRI plus cetuximab group than the FOLFIRI plus bevacizumab group (331 months [95% CI 245-394] vs 250 months [230-281]; hazard ratio 070 [054-090]; p=00059), although investigator-assessed objective response and progression-free survival were comparable between treatment groups. Centralised radiological review of CT-assessable patients (n=330) showed that the proportion of patients achieving an objective response (113 of 157, 720% [95% CI 643-788] vs 97 of 173, 561% [483-636]; p=00029), frequency of early tumour shrinkage (107 of 157, 682% [603-754] vs 85 of 173, 491% [415-568]; p=00005), and median depth of response (-489% [-543 to -420] vs -323% [-382 to -292]; p<00001) were significantly better in extended RAS wild-type patients receiving FOLFIRI plus cetuximab versus those receiving FOLFIRI plus bevacizumab. No differences in duration of response and time to response were observed between treatment groups.This analysis provides a new framework that connects alternative metrics of response to overall survival. Superior response-related outcome parameters, such as early tumour shrinkage and depth of response, obtained by centralised radiological review correlated with the overall survival benefit conferred by FOLFIRI plus cetuximab compared with FOLFIRI plus bevacizumab in the extended RAS wild-type subgroup.Merck KGaA and Pfizer.


Iacobone M.,University of Padua | Jansson S.,Sahlgrenska University Hospital | Barczynski M.,Jagiellonian University | Goretzki P.,Lukaskrankenhaus Neuss
Langenbeck's Archives of Surgery | Year: 2014

Background: Multifocal papillary thyroid carcinoma (MPTC) has been reported in literature in 18-87 % of cases. This paper aims to review controversies in the molecular pathogenesis, prognosis, and management of MPTC. Methods: A review of English-language literature focusing on MPTC was carried out, and analyzed in an evidence-based perspective. Results were discussed at the 2013 Workshop of the European Society of Endocrine Surgeons devoted to surgery of thyroid carcinoma. Results: Literature reports no prospective randomized studies; thus, a relatively low level of evidence may be achieved. Conclusions: MPTC could be the result of either true multicentricity or intrathyroidal metastasis from a single malignant focus. Radiation and familial nonmedullary thyroid carcinoma are conditions at risk of MPTC development. The prognostic importance of multifocal tumor growth in PTC remains controversial. Prognosis might be impaired in clinical MPTC but less or none in MPTC <1 cm. MPTC can be diagnosed preoperatively by FNAB and US, with low sensitivity for MPTC <1 cm. Total or near-total thyroidectomy is indicated to reduce the risk of local recurrence. Prophylactic central node dissection should be considered in patients with total tumor diameter >1 cm, or in cases with high number of cancer foci. Completion thyroidectomy might be necessary when MPTC is diagnosed after less than near-total thyroidectomy. Radioactive iodine ablation should be considered in selected patients with MPTC at increased risk of recurrence or metastatic spread. © 2013 Springer-Verlag.


Musholt T.J.,University Hospital Freiburg | Clerici T.,Kantonsspital St. Gallen | Dralle H.,Martin Luther University of Halle Wittenberg | Frilling A.,Imperial College London | And 17 more authors.
Langenbeck's Archives of Surgery | Year: 2011

Introduction: Benign thyroid disorders are among the most common diseases in Germany, affecting around 15 million people and leading to more than 100,000 thyroid surgeries per year. Since the first German guidelines for the surgical treatment of benign goiter were published in 1998, abundant new information has become available, significantly shifting surgical strategy towards more radical interventions. Additionally, minimally invasive techniques have been developed and gained wide usage. These circumstances demanded a revision of the guidelines. Methods: Based on a review of relevant recent guidelines from other groups and additional literature, unpublished data, and clinical experience, the German Association of Endocrine Surgeons formulated new recommendations on the surgical treatment of benign thyroid diseases. These guidelines were developed through a formal expert consensus process and in collaboration with the German societies of Nuclear Medicine, Endocrinology, Pathology, and Phoniatrics & Pedaudiology as well as two patient organizations. Consensus was achieved through several moderated conferences of surgical experts and representatives of the collaborating medical societies and patient organizations. Results: The revised guidelines for the surgical treatment of benign thyroid diseases include recommendations regarding the preoperative assessment necessary to determine when surgery is indicated. Recommendations regarding the extent of resection, surgical techniques, and perioperative management are also given in order to optimize patient outcomes. Conclusions: Evidence-based recommendations for the surgical treatment of benign thyroid diseases have been created to aid the surgeon and to support optimal patient care, based on current knowledge. These recommendations comply with the Association of the Scientific Medical Societies in Germany requirements for S2k guidelines. © Springer-Verlag 2011.


Background. Due to the relatively low incidence of the diseases the diagnostic procedures for tumors of the vulva and vagina are continually under discussion. Aim. Diagnostic procedures should lead to the most effective and safe treatment plan with as little stress as possible. Methods. The appropriate literature and clinical experience are combined for optimizing the diagnostic schedule. Results and discussion. The main tool for examination is clinical inspection and palpation. The histological results of the primary tumor and, if necessary imaging of lymph nodes, are essential for deciding on the treatment plan. The diagnostic procedures should be indicated depending on the position and the dimensions of the primary tumor whereby the position in relation to the middle line, surface diameter of the tumor and depth of infiltration are of special interest. Radiological examinations, such as computed tomography (CT), magnetic resonance imaging (MRI) and endosonography should be used to clarify the local topography of the primary towards urethra, bladder, rectum and anus/ sphincter. Investigations should concentrate on the regional inguinofemoral lymph nodes as the first site of metastasis followed by the pelvic nodes and in advanced primary tumors the para-aortic and mediastinal lymph nodes should also be clarified. Distant metastases may occur in advanced tumors. In these cases CT is indicated for examination of the para-aortic and mediastinal lymph nodes as well as the liver and the lungs. © Springer-Verlag 2014.


Wirowski D.,Lukaskrankenhaus Neuss | Goretzki P.E.,Lukaskrankenhaus Neuss | Schwarz K.,Lukaskrankenhaus Neuss | Lammers B.J.,Lukaskrankenhaus Neuss
Langenbeck's Archives of Surgery | Year: 2013

Purpose: Since its registration in 2004, the calcimimetic agent cinacalcet has been established as an alternative treatment for secondary hyperparathyroidism (SHPT). Working by allosteric activation of the calcium-sensing receptor, cinacalcet can lower parathyroid hormone (PTH) and calcium (Ca) in patients with SHPT. The influence of calcimimetics on the perioperative course has been unclear so far. Methods: We retrospectively analyzed the data of patients with primary operation for SHPT between 2004 and 2011, comparing the perioperative course of patients with and without preoperative cinacalcet treatment. Results: Fifty-six patients had cinacalcet therapy, and 54 patients had no calcimimetic medication prior to surgery. Gender, age, hemodialysis, and medical treatment were similar in both groups. Also, PTH levels were similar preoperatively and postoperatively (preoperative, 1,249 ± 676 vs. 1,196 ± 601 pg/ml; postoperative, 86 ± 220 vs. 62 ± 91 pg/ml). Patients with cinacalcet preoperatively had significant lower Ca levels preoperatively (2.49 ± 0.25 vs. 2.61 ± 0.24 mmol/l) and postoperatively (1.75 ± 0.37 vs. 1.86 ± 0.35 mmol/l) and had a higher rate of oral Ca substitution postoperatively (93 vs. 74 %). The risk for postoperative persistent disease was slightly higher in these patients compared to those without preoperative cinacalcet therapy (5 vs. 0 %, not significant). Conclusions: In our experience, cinacalcet did not alter the perioperative course in SHPT patients. © 2012 Springer-Verlag.


PubMed | Lukaskrankenhaus Neuss
Type: Comparative Study | Journal: Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association | Year: 2013

Advanced preoperative imaging of parathyroid adenomas and intraoperative parathyroid hormone determination optimized the results in the surgical treatment of primary hyperparathyroidism patients. We asked, whether reasons for failure have changed during the last 25 years.We retrospectively analyzed operations for persistent primary hyperparathyroidism in our department between 2001 and 2011 (n=67), and compared these results to our experience between 1986 and 2001 (n=80).From 2001 to 2011, 765 primary hyperparathyroidism patients were operated on at our department. All but 4 patients were cured (761/765, 99.5%). 67 operations were performed for persistent primary hyperparathyroidism. Main reasons for failure were a misdiagnosed sporadic multiple gland disease in our own patients (18/29, 62.1%), and an undetected solitary adenoma in patients referred to us after -initial operation in another hospital (22/38, 57.9%) (statistically significant). From 1986 to 2001 (1 105 primary hyperparathyroidism patients), main indications for re-operation due to persistent disease were an undiagnosed sporadic multiple gland disease in our own patients (15/24, 62.5%), and a missed solitary adenoma in patients being operated on primarily somewhere else (38/56, 67.9%) (statistically significant).Comparing our experience in 147 patients with persistent primary hyperparathyroidism being operated on between 2001-2011 and 1986-2001, not much has changed with the modern armamentarium of improved preoperative imaging or intraoperative biochemical control. Whereas sporadic multiple gland disease was the most common reason for unsuccessful surgery in experienced hands, other units mainly failed due to an undetected solitary adenoma. Re-operations for persistent primary hyperparathyroidism performed by us were successful in 93.8% (2001-2011) and 96.0% (1986-2001), respectively.


PubMed | Lukaskrankenhaus Neuss
Type: | Journal: European journal of medical research | Year: 2013

In recent years, many advances in pancreatic surgery have been achieved. Nevertheless, the rate of pancreatic fistula following pancreatic tail resection does not differ between various techniques, still reaching up to 30% in prospective multicentric studies. Taking into account contradictory results concerning the usefulness of covering resection margins after distal pancreatectomy, we sought to perform a systematic, retrospective analysis of patients that underwent distal pancreatectomy at our center.We retrospectively analysed the data of 74 patients that underwent distal pancreatectomy between 2001 and 2011 at the community hospital in Neuss. Demographic factors, indications, postoperative complications, surgical or interventional revisions, and length of hospital stay were registered to compare the outcome of patients undergoing distal pancreatectomy with coverage of the resection margins vs. patients undergoing distal pancreatectomy without coverage of the resection margins. Differences between groups were calculated using Fishers exact and Mann-Whitney U test.Main indications for pancreatic surgery were insulinoma (n=18, 24%), ductal adenocarcinoma (n=9, 12%), non-single-insulinoma-pancreatogenic-hypoglycemia-syndrome (NSIPHS) (n=8, 11%), and pancreatic cysts with pancreatitis (n=8, 11%). In 39 of 74 (53%) patients no postoperative complications were noted. In detail we found that 23/42 (55%) patients with coverage vs. 16/32 (50%) without coverage of the resection margins had no postoperative complications. The most common complications were pancreatic fistulas in eleven patients (15%), and postoperative bleeding in nine patients (12%). Pancreatic fistulas occurred in patients without coverage of the resection margins in 7/32 (22%) vs. 4/42 (1011%) with coverage are of the resection margins, yet without reaching statistical significance. Postoperative bleeding ensued with equal frequency in both groups (12% with coverage versus 13% without coverage of the resection margins). The reoperation rate was 8%. The hospital stay for patients without coverage was 13 days (5-60) vs. 17 days (8-60) for patients with coverage.The results show no significant difference in the fistula rate after covering of the resection margin after distal pancreatectomy, which contributes to the picture of an unsolved problem.

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