Stuttgart, Germany
Stuttgart, Germany

Time filter

Source Type

Braun N.,Robert Bosch GmbH | Braun N.,Institute of Digital Medicine | Sen K.,University Hospital | Sen K.,University of Zürich | And 14 more authors.
Peritoneal Dialysis International | Year: 2013

Background: Periostin is a matricellular protein involved in tissue remodeling through the promotion of adhesion, cell survival, cellular dedifferentiation, and fibrogenesis. It can be induced by transforming growth factor beta and high glucose concentrations. We hypothesized that this protein might be expressed in the peritoneal cavity of patients on peritoneal dialysis (PD) and even more in patients with signs of encapsulating peritoneal sclerosis (EPS). Method: In this retrospective study, we included peritoneal biopsies from patients on PD with EPS (n = 7) and without signs of EPS (n = 10), and we compared them with biopsies taken during hernia repair from patients not on PD (n = 11) and during various procedures from uremic patients not on PD (n = 6). Periostin was localized by immunohistochemistry, scored semiquantitatively, and quantified by morphometry. Periostin protein concentrations were measured by ELISA in dialysates from 15 patients. Periostin messenger RNA was quantified in vitro in peritoneal fibroblasts. Results: In control biopsies, periostin was present in the walls of larger arteries and focally in extracellular matrix in the submesothelial zone. Patients on PD demonstrated interstitial periostin in variable amounts depending on the severity of submesothelial fibrosis. In EPS, periostin expression was very prominent in the sclerosis layer. The area of periostin was significantly larger in EPS biopsies than in control biopsies, and the percentage of periostin-positive area correlated with the thickness of the submesothelial fibrosis zone. Periostin concentrations in dialysate increased significantly with time on PD in patients without signs of EPS; in patients with EPS, periostin concentrations in dialysate were low and demonstrated the smallest increase with time. In vitro, periostin was found to be strongly expressed by peritoneal fibroblasts. Conclusion: Periostin is strongly expressed by fibroblasts and deposited in the peritoneal cavity of patients with EPS and with simple peritoneal fibrosis on PD. This protein might play a role in the progression of peritoneal injury, and low levels of periostin after prolonged time on PD might be a marker of EPS. © 2013 International Society for Peritoneal Dialysis.


PubMed | Robert Bosch GmbH, University of Tübingen, University of Stuttgart, Institute of Digital Medicine and 4 more.
Type: Journal Article | Journal: Anticancer research | Year: 2014

The well-characterized tubular-type of breast tumors is classified as low-risk breast cancer.We report on the results of a retrospective analysis on clinical and biological features of 248 tubular breast tumors including follow-up and treatment data from two German series of 21,065 breast cancer cases. The majority of tumors were stage I or stage II, ER- and PR-positive and c-erbB2-negative with a 5-year survival-rate of 96.3%. 51.3% of patients received hormonal treatment, 75.5% had post-operative radiotherapy and 11.8% were treated with a chemotherapeutical regimen.Our retrospective analysis showed no treatment benefit for either anti-hormonal or chemotherapeutical regimens. Post-operative radiotherapy, however, improved the survival rate of patients with tubular carcinoma (log-rank=5, p=0.025). Our data suggest that post-operative radiotherapy is an important treatment to prolong survival for patients suffering from tubular breast cancer.


Latus J.,Robert Bosch GmbH | Ulmer C.,Robert Bosch GmbH | Fritz P.,Institute of Digital Medicine | Rettenmaier B.,Robert Bosch GmbH | And 8 more authors.
Peritoneal Dialysis International | Year: 2013

Background: Encapsulating peritoneal sclerosis (EPS) is a rare but devastating complication of peritoneal dialysis (PD), with clinical signs of abdominal pain, bowel obstruction, and weight loss in late stages. Methods: We retrospectively analyzed all patients who were diagnosed with EPS between March 1998 and October 2011 in our department of nephrology. We focused on the 24 EPS patients who underwent surgery because of symptomatic late-stage EPS. We identified 3 different macroscopic phenotypes of EPS that we categorized as typesIIII. We correlated histologic findings with those macroscopic phenotypes of EPS. The postoperative and long-term outcomes were evaluated by macroscopic phenotype. Results: Duration of PD was longer in type III than in types I and II EPS (p = 0.05). We observed no other statistically significant differences between the groups in baseline characteristics, except for operation time, which was longer in the typeI than in the typeIII group (p= 0.02). Furthermore, we observed no statistically significant difference between the groups with respect to the onset of complaints before surgery (7.8 ± 5.9 months vs 7.0 ± 7.0 months vs 6.5 ±5.3 months). Concerning patient outcomes, there was no evidence that any of the macroscopic EPS types was associated with more major or minor complications after surgery. For all study patients, follow-up was at least 3 years, with 19 patients still being alive, and 16 having no or very mild complaints. The typical histologic findings of EPS were present in all macroscopic types; only fibrin deposits were more prominent in typeII than in typeIII. Conclusions: We describe 3 subtypes of EPS based on macroscopic findings. Postoperative treatment should probably not be influenced by the macroscopic EPS phenotype. Whether the different phenotypes represent different pathophysiologic processes remains unclear and has to be further evaluated. © 2013 International Society for Peritoneal Dialysis.


Braun N.,Robert Bosch GmbH | Alscher M.D.,Robert Bosch GmbH | Alscher M.D.,Institute of Digital Medicine | Fritz P.,Institute of Digital Medicine | And 12 more authors.
PLoS ONE | Year: 2012

Encapsulating peritoneal sclerosis (EPS) is a life threatening complication of peritoneal dialysis (PD). Podoplanin is a glycoprotein expressed by mesothelial cells, lymphatic endothelial cells, and myofibroblasts in peritoneal biopsies from patients with EPS. To evaluate podoplanin as a marker of EPS we measured podoplanin mRNA and described the morphological patterns of podoplanin-positive cells in EPS. Included were 20 peritoneal biopsies from patients with the diagnosis of EPS (n = 5), patients on PD without signs of EPS (n = 5), and control patients (uremic patients not on PD, n = 5, non-uremic patients n = 5). EPS patient biopsies revealed significantly elevated levels of podoplanin mRNA (p<0.05). In 24 peritoneal biopsies from patients with EPS, podoplanin and smooth muscle actin (SMA) were localized by immunohistochemistry. Four patterns of podoplanin distribution were distinguishable. The most common pattern (8 of 24) consisted of organized, longitudinal layers of podoplanin-positive cells and vessels in the fibrotic zone ("organized" pattern). 7 of 24 biopsies demonstrated a diffuse distribution of podoplanin-positive cells, accompanied by occasional, dense clusters of podoplanin-positive cells. Five biopsies exhibited a mixed pattern, with some diffuse areas and some organized areas ("mixed"). These contained cuboidal podoplanin-positive cells within SMA-negative epithelial structures embedded in extracellular matrix. Less frequently observed was the complete absence of, or only focal accumulations of podoplanin-positive fibroblasts outside of lymphatic vessels (podoplanin "low", 4 of 24 biopsies). Patients in this group exhibited a lower index of systemic inflammation and a longer symptomatic period than in EPS patients with biopsies of the "mixed" type (p<0.05). In summary we confirm the increased expression of podoplanin in EPS, and distinguish EPS biopsies according to different podoplanin expression patterns which are associated with clinical parameters. Podoplanin might serve as a useful adjunct to the morphological workup of peritoneal biopsies. © 2012 Braun et al.


Seeger H.,University of Zürich | Braun N.,Robert Bosch GmbH | Latus J.,Robert Bosch GmbH | Alscher M.D.,Robert Bosch GmbH | And 6 more authors.
Nephron - Clinical Practice | Year: 2014

Introduction: Simple peritoneal fibrosis and encapsulating peritoneal sclerosis (EPS) are important lesions in the peritoneum of patients on peritoneal dialysis (PD). We have previously described a population of podoplanin-positive myofibroblasts in peritoneal biopsies from patients with EPS. Platelet-derived growth factor receptor-β (PDGFRβ) is a marker of pericytes, and PDGFs might be involved in the fibrotic response of the peritoneum. This study aimed to describe PDGFRβ in the human peritoneum. Methods: In this retrospective analysis, we localized PDGFRβ in peritoneal biopsies from patients with EPS (n = 6) and patients on PD without signs of EPS (n = 5), and compared them with normal peritoneum (n = 4) and peritoneum from uremic patients (n = 5). Consecutive sections were stained for smooth-muscle actin (SMA) and podoplanin. Slides were scored semiquantitatively by 2 observers blinded to the diagnosis. Results: PDGFRβ was expressed by cells of arterial walls in all biopsies. A prominent population of PDGFRβ-positive cells was present in the normal peritoneum, which were SMA negative on consecutive sections. In patients on PD, a high number of PDGFRβ were also positive for SMA. In EPS, the majority of podoplanin-positive cells were positive for PDGFRβ. In peritoneal biopsies from normal and uremic patients, the expression of SMA was mainly restricted to cells of arterial walls. Podoplanin expression was restricted to lymphatic vessels in normal peritoneum, in uremic patients, and in patients on PD without EPS. Conclusions: As podoplanin-positive myofibroblasts express PDGFRβ, these cells might be related to pericytes (rather than other sources of fibroblasts). PDGFRβ might turn out to be a therapeutic target in EPS. © 2014 S. Karger AG, Basel.


Friedel G.,Klinik Schillerhohe Center for Pneumology and Thoracic Surgery | Fritz P.,Institute of Digital Medicine | Fritz P.,Robert Bosch GmbH | Goletz S.,Robert Bosch GmbH | And 7 more authors.
Anticancer Research | Year: 2013

Background/Aim: We report on survival data of 595 patients with stage I-III lung cancer with respect to TNM classification. Materials and Methods: We constructed a basic model consisting of stage and grade, and assessed the improvement of survival prediction after adding comorbidity data, spirometric data, clinical and laboratory parameters. Results: Body mass index (BMI) and presence of a cardiac disease reached statistical significance for prediction of overall survival in a Cox regression model. In addition to BMI (<25 kg/m2) and the presence of cardiovascular disease, the spirometric variable (FEV1) predicted early death (less than five months postoperatively). When the survival random forest method was employed to predict disease outcome, creatinine levels and VO2 max became additional variables of interest for predicting survival. Conclusion: We propose that our lung cancer database may help to identify variables (aside from histomorphological variables) that are suitable for identifying patients at risk of death after surgical treatment of lung cancer.


Fritz P.,Institute of Digital Medicine | Fritz P.,Robert Bosch GmbH | Klenk S.,Institute of Digital Medicine | Goletz S.,Institute of Digital Medicine | And 10 more authors.
Anticancer Research | Year: 2010

Background: Treatment decisions in breast cancer depend on TNM classification and the assessment of additional variables with have an impact on survival. We examined whether histological subtyping breast cancer as either ductal or lobular is related to disease outcome. Patients and Methods: We examined a large data base of 14198 breast cancer patients. Results: Histological subclassification of invasive breast cancer as either ductal or lobular is not correlated with disease outcome. However, the data further showed that invasive lobular carcinomas have a higher probability of being oestrogen receptor (ER)and progesterone receptor (PR)-positive and a lower probability of being c-erbB2-positive. They also showed a higher average age at the time of diagnosis in comparison with invasive ductal carcinoma. Local recurrence rates were lower in invasive lobular carcinoma in comparison with invasive ductal carcinoma (3.5% vs. 6.2%; p=0.031). The multivariable Cox regression analysis showed that ER, PR, nodal status, grade and tumour size predicted disease outcome with statistical significance, while the histological subtype (invasive ductal or lobular) was not a significant predictor of disease outcome. Conclusion: Histological subclassification of invasive breast cancer as either ductal or lobular is not correlated with disease outcome. On the other hand our data gives some indication that lobular and ductal breast cancer appear to be different biological entities.


Latus J.,Robert Bosch GmbH | Klein R.,University Hospital of Tuebingen | Koetter I.,Robert Bosch GmbH | Schwab M.,Robert Bosch GmbH | And 4 more authors.
PLoS ONE | Year: 2013

Background: Millions of patients are treated with therapeutic monoclonal antibodies (Tmabs) for miscellaneous diseases. We investigated sera from six patients who received immune globulin, from one patient with refractory anti-neutrophilcytoplasmic antibody (ANCA)-associated granulomatosis with polyangiitis (GPA) who developed two episodes of acute cholestatic liver disease, one after treatment with rituximab and a second after adalimumab and a healthy control group. Methods: Three sera from the patient and six sera from patients who received immune globulin were analyzed for antibodies to rituximab and adalimumab by ELISA. Additionally, sera from the patients and from nine healthy blood donors were coated with the Fab fragment of an unrelated humanized monoclonal antibody, with human Fc proteins as well as a mouse IgG globulin. Results: Viral serology for hepatitis A, B, C and autoantibodies specific for autoimmune liver disorders were negative. In all three sera from the patient antibodies to rituximab could be detected, but also antibodies to adalimumab were present even at time points when the patient had not yet received adalimumab, indicating cross reactivity between both substances. Testing against an unrelated human Fab fragment revealed positive results, indicating that the patient had antibodies against human Fab fragments in general. The Fc proteins were negative, and patients' sera did also not react with mouse IgG globulins. Remarkably, 2 out of 5 patients which were treated with immune globulin had antibodies against human Fab fragments in general whereas in none of the samples from healthy controls antibodies to Fab fragment could be detected. Conclusion: This is the first study demonstrating cholestatic liver disease induced by two different Tmabs. Cross - reacting antibodies to Fab2 fragments in general are probably involved. Further studies must show if these Fab2 antibodies in general are related with drug-induced side effects and accelerated drug clearance in patients on Tmab therapy. © 2013 Latus et al.


Braun N.,Robert Bosch GmbH | Braun N.,Institute of Digital Medicine | Alscher D.M.,Robert Bosch GmbH | Alscher D.M.,Institute of Digital Medicine | And 11 more authors.
Nephrology Dialysis Transplantation | Year: 2011

Background: Encapsulating peritoneal sclerosis (EPS) and simple peritoneal sclerosis are important complications of long-term peritoneal dialysis (PD). Podoplanin is expressed by mesothelial cells and lymphatic vessels, which are involved in inflammatory reactions in the peritoneal cavity.Methods. We studied 69 peritoneal biopsies from patients on PD (n = 16), patients with EPS (n = 18) and control biopsies taken at the time of hernia repair (n = 15) or appendectomy (n = 20). Immunohistochemistry was performed to localize podoplanin. Additionally, markers of endothelial cells, mesothelial cells, myofibroblasts (smooth muscle actin), proliferating cells, and double labelling for smooth muscle actin/podoplanin were used on selected biopsies.Results. Podoplanin was present on the endothelium of lymphatic vessels in the submesothelial fibrous tissue and on mesothelial cells. In patients on PD and in biopsies with appendicitis, the mesothelial cells demonstrated a cuboidal appearance and circumferential podoplanin staining, with gaps between the cells. The number of lymphatic vessels was variable, but prominent at sites of fibrosis. In patients with EPS, a diffuse infiltration of podoplanin-positive cells with a fibroblastic appearance was present in 15 out of 18 biopsies. This pattern was focally present in 3 out of 16 on PD and none in the 35 controls. The podoplanin-positive cells did not express the endothelial marker or the mesothelial marker (calretinin).Conclusions. EPS is characterized by a population of podoplanin and smooth muscle actin double-positive cells. Podoplanin might be a suitable morphological marker supporting the diagnosis and might be involved in the pathogenesis of EPS. © The Author 2011. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.


PubMed | Institute of Digital Medicine
Type: Journal Article | Journal: Anticancer research | Year: 2010

Treatment decisions in breast cancer depend on TNM classification and the assessment of additional variables with have an impact on survival. We examined whether histological subtyping breast cancer as either ductal or lobular is related to disease outcome.We examined a large data base of 14198 breast cancer patients.Histological sub-classification of invasive breast cancer as either ductal or lobular is not correlated with disease outcome. However, the data further showed that invasive lobular carcinomas have a higher probability of being oestrogen receptor (ER)- and progesterone receptor (PR)-positive and a lower probability of being c-erbB2-positive. They also showed a higher average age at the time of diagnosis in comparison with invasive ductal carcinoma. Local recurrence rates were lower in invasive lobular carcinoma in comparison with invasive ductal carcinoma (3.5% vs. 6.2%; p = 0.031). The multivariable Cox regression analysis showed that ER, PR, nodal status, grade and tumour size predicted disease outcome with statistical significance, while the histological subtype (invasive ductal or lobular) was not a significant predictor of disease outcome.Histological sub-classification of invasive breast cancer as either ductal or lobular is not correlated with disease outcome. On the other hand our data gives some indication that lobular and ductal breast cancer appear to be different biological entities.

Loading Institute of Digital Medicine collaborators
Loading Institute of Digital Medicine collaborators