Publications by authors named "Thore Thiesler"

19 Publications

  • Page 1 of 1

Sarcoidosis of the paranasal sinuses.

Eur Arch Otorhinolaryngol 2019 Jul 21;276(7):1969-1974. Epub 2019 Mar 21.

Department of Otorhinolaryngology, Munich University (LMU), Munich, Germany.

Background: Sarcoidosis is a chronic disease, which predominantly affects the lung. Since sinonasal sarcoidosis is rare, little is known about the sarcoidosis manifestation at this site. Therefore, the aim of our study was to detect the prevalence of sinonasal sarcoidosis, its clinical occurrence, diagnosis, and therapy.

Methods: The database of all patients having visited the otorhinolaryngology departments of the universities in Göttingen and in Bonn between 2003 and 2016 was searched for the diagnosis of sinonasal sarcoidosis.

Results: Thirteen patients with a biopsy-proven sinonasal sarcoidosis were identified. Most patients presented non-specific clinical symptoms, which are also found in acute and chronic sinusitis. None of the patients was suspected to have sinonasal sarcoidosis by the ENT doctor before histological validation. The mean diagnostic delay was 262 (± 195) days. An additional pulmonary involvement was detected in four of six patients.

Conclusions: Sinonasal sarcoidosis is presenting with heterogeneous clinical presentations. An early biopsy of granulomatous lesions is mandatory. A multidisciplinary approach is needed to exclude serious lung or heart manifestations, because even asymptomatic organ involvement is possible. A CT-scan may be useful even if unspecific. Local or systemic therapy has to be prepared individually using local and systemic corticosteroids, antimetabolites, or anti-TNF-alpha.
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http://dx.doi.org/10.1007/s00405-019-05388-7DOI Listing
July 2019

Quantitative perineural invasion is a prognostic marker in prostate cancer.

Pathology 2018 Apr 12;50(3):298-304. Epub 2018 Feb 12.

Institute of Pathology of the University Hospital Bonn, Bonn, Germany. Electronic address:

This study aimed to investigate the prognostic value of a quantitative, detailed, yet practical analysis of perineural invasion in radical prostatectomy specimens in a high-risk prostate cancer cohort. A total of 114 patients with prostate cancer who underwent radical prostatectomy between 2000 and 2013 were analysed. Using S100 protein immunohistochemistry assisted in the detection of nerves. In the area of closest proximity of the tumour to the dorso-lateral margins, nerves were counted and the infiltration of nerves was categorised (0-3). Category 0 was nerves without immediate tumour-cell-contact. All nerves being fully surrounded by tumour (classical perineural carcinosis) were categorised group 3. Two further categories discriminated between nerves that were touched either by carcinoma cells below 50% of the circumference (category 1) or above (category 2). Perineural carcinosis (Pn1) was seen in 61.4% of cases and correlated positively with ISUP grades, pT categories and presence of intraductal carcinoma but failed significance on Kaplan-Meier analysis. A more quantitative analysis of percentual perineural involvement did demonstrate significant survival differences: cases with less than one Pn1-positive nerve in 5 high power fields had longer survival times. Incomplete perineural involvement (category 1-2) did not have a prognostic value, endorsing the current definition of perineural carcinosis as full circumferential encasement of a nerve by tumour cells. A quantitative analysis of the percentage of nerves positive for perineural invasion has a higher prognostic value than the classical dichotomous statement on the mere presence of perineural invasion.
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http://dx.doi.org/10.1016/j.pathol.2017.09.013DOI Listing
April 2018

Tumoral PD-L1 expression defines a subgroup of poor-prognosis vulvar carcinomas with non-viral etiology.

Oncotarget 2017 Nov 6;8(54):92890-92903. Epub 2017 Oct 6.

Department of Obstetrics and Gynecology, Center for Integrated Oncology, University of Bonn, Bonn, Germany.

Vulvar cancer is rare but incidence rates are increasing due to an aging population and higher frequencies of young women being affected. In locally advanced, metastatic or recurrent disease prognosis is poor and new treatment modalities are needed. Immune checkpoint blockade of the PD-1/PD-L1 pathway is one of the most important advancements in cancer therapy in the last years. The clinical relevance of PD-L1 expression in vulvar cancer, however, has not been studied so far. We determined PD-L1 expression, numbers of CD3 T cells, CD20 B cells, CD68 monocytes/macrophages, Foxp3 regulatory T cells and CD163 tumor-associated macrophages by immunohistochemistry in 103 patients. Correlation analysis with clinicopathological parameters was undertaken; the cause-specific outcome was modeled with competing risk analysis; multivariate Cox regression was used to determine independent predictors of survival. Membranous PD-L1 was expressed in a minority of tumors, defined by HPV-negativity. Its presence geographically correlated with immunocyte-rich regions of cancer islets and was an independent prognostic factor for poor outcome. Our data support the notion that vulvar cancer is an immunomodulatory tumor that harnesses the PD-1/PD-L1 pathway to induce tolerance. Accordingly, immunotherapeutic approaches might have the potential to improve outcome in patients with vulvar cancer and could complement conventional cancer treatment.
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http://dx.doi.org/10.18632/oncotarget.21641DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5696230PMC
November 2017

Impact of Chemotherapy on Retroperitoneal Lymph Nodes in Ovarian Cancer.

Anticancer Res 2016 Apr;36(4):1815-24

Department of Gynecology and Obstetrics, Center for Integrated Oncology Cologne Bonn, University of Bonn, Bonn, Germany.

Background: Complete cytoreduction is the most important prognostic factor in ovarian cancer. However, there exist conflicting data on whether the removal of microscopic tumor metastasis in macroscopically unsuspicious retroperitoneal lymph nodes is beneficial.

Patients And Methods: Ovarian cancer tissues and tissues from lymph node metastasis of 30 patients with FIGO IIIC or IV disease undergoing neoadjuvant chemotherapy (NACT) were obtained and assessed using a validated regression score. Histopathological markers, size of largest tumor focus, and overall score were evaluated in lymph node and ovarian tissue. Regression and known prognostic factors were analyzed for influence on survival.

Results: No difference in the overall score between lymph nodes and ovarian tissue was shown, however, single parameters such as fibrosis and pattern of tumor infiltration, were significantly different.

Conclusion: The pattern of tumor regression in lymph nodes and ovarian tissue are of prognostic value. Lymph node dissection even of unsuspicious nodes should, therefore, be performed.
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April 2016

The IL-33/ST2 pathway contributes to intestinal tumorigenesis in humans and mice.

Oncoimmunology 2016;5(1):e1062966. Epub 2015 Jun 26.

Institute of Pathology, University of Bern , Bern, Switzerland.

Colorectal cancer (CRC) develops through a multistep process and is modulated by inflammation. However, the inflammatory pathways that support intestinal tumors at different stages remain incompletely understood. Interleukin (IL)-33 signaling plays a role in intestinal inflammation, yet its contribution to the pathogenesis of CRC is unknown. Using immunohistochemistry on 713 resected human CRC specimens, we show here that IL-33 and its receptor ST2 are expressed in low-grade and early-stage human CRCs, and to a lesser extent in higher-grade and more advanced-stage tumors. In a mouse model of CRC, ST2-deficiency protects from tumor development. Moreover, bone marrow (BM) chimera studies indicate that engagement of the IL-33/ST2 pathway on both the radio-resistant and radio-sensitive compartment is essential for CRC development. Mechanistically, activation of IL-33/ST2 signaling compromises the integrity of the intestinal barrier and triggers the production of pro-tumorigenic IL-6 by immune cells. Together, this data reveals a tumor-promoting role of IL-33/ST2 signaling in CRC.
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http://dx.doi.org/10.1080/2162402X.2015.1062966DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4760343PMC
June 2015

Individual management of cervical cancer in pregnancy.

Arch Gynecol Obstet 2016 May 4;293(5):931-9. Epub 2016 Jan 4.

Department of Gynecology, Center for Integrated Oncology, University of Bonn, Sigmund-Freud-Strasse 25, 53127, Bonn, Germany.

Purpose: The management of cervical cancer in pregnancy persists to be challenging. Therefore, identification of factors that influence the choice of therapeutic management is pivotal for an adequate patient counseling.

Methods: We present a literature review of 26 studies reporting 121 pregnancies affected by cervical cancer. Additionally, we add a retrospective case series of five patients with pregnancy-associated cervical cancer diagnosed and treated in our clinic between 2006 and 2013.

Results: The literature review revealed that the therapeutic management during pregnancy varies according to the gestational age at diagnosis, while in the postpartum period no influence on the treatment choice could be detected. Also in our case series the choice of oncologic therapy was influenced by the gestational age, the wish to continue the pregnancy and the risks of delaying definitive treatment.

Conclusions: There are no standardized procedures concerning the treatment of cervical cancer in pregnancy. Therefore, in consultation with the patient and a multidisciplinary team, an adequate individualized treatment plan should be determined.
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http://dx.doi.org/10.1007/s00404-015-3980-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4829625PMC
May 2016

The Immune Checkpoint Regulator PD-L1 Is Highly Expressed in Aggressive Primary Prostate Cancer.

Clin Cancer Res 2016 Apr 16;22(8):1969-77. Epub 2015 Nov 16.

Institute of Pathology, University Hospital Bonn, Bonn, Germany.

Purpose: Therapies targeting the programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) pathway promote anti-tumor immunity and have shown promising results in various tumors. Preliminary data further indicate that immunohistochemically detected PD-L1 may be predictive for anti-PD-1 therapy. So far, no data are available on PD-L1 expression in primary prostate cancer.

Experimental Design: Following validation of a monoclonal antibody, immunohistochemical analysis of PD-L1 expression was performed in two independent, well-characterized cohorts of primary prostate cancer patients following radical prostatectomy (RP), and resulting data were correlated to clinicopathological parameters and outcome.

Results: In the training cohort (n= 209), 52.2% of cases expressed moderate to high PD-L1 levels, which positively correlated with proliferation (Ki-67,P< 0.001), Gleason score (P= 0.004), and androgen receptor (AR) expression (P< 0.001). Furthermore, PD-L1 positivity was prognostic for biochemical recurrence [BCR;P= 0.004; HR, 2.37; 95% confidence interval (CI), 1.32-4.25]. In the test cohort (n= 611), moderate to high PD-L1 expression was detected in 61.7% and remained prognostic for BCR in univariate Cox analysis (P= 0.011; HR, 1.49; 95% CI, 1.10-2.02). The correlation of Ki-67 and AR with PD-L1 expression was confirmed in the test cohort (P< 0.001). In multivariate Cox analysis of all patients, PD-L1 was corroborated as independently prognostic for BCR (P= 0.007; HR, 1.46; 95% CI, 1.11-1.92).

Conclusions: We provide first evidence that expression of the therapy target PD-L1 is not only highly prevalent in primary prostate cancer cells but is also an independent indicator of BCR, suggesting a biologic relevance in primary tumors. Further studies need to ascertain if PD-1/PD-L1-targeted therapy might be a treatment option for hormone-naïve prostate cancers.
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http://dx.doi.org/10.1158/1078-0432.CCR-15-2042DOI Listing
April 2016

Effect of Peripheral Artery Sympathetic Denervation on Muscle Microperfusion and Macroperfusion in an Animal Peripheral Artery Disease Model Using Contrast-Enhanced Ultrasound and Doppler Flow Measurement.

J Vasc Interv Radiol 2015 Sep 17;26(9):1396-402.e2. Epub 2015 Jul 17.

Radiology, University of Bonn, Bonn, Germany. Electronic address:

Purpose: To determine the effects of catheter-based peripheral sympathetic denervation (CPSD) on peripheral artery sympathetic tone and peripheral microperfusion (PMP).

Materials And Methods: The effects of bilateral CPSD in common iliac arteries on PMP of the biceps femoris were determined in pigs using contrast-enhanced ultrasound, and mean transit time (mTT) and wash-in rate (WiR) were calculated during steady-state infusion of INN-sulfur-hexafluoride. Measurements were performed bilaterally at rest and during infusion of adenosine 70 μg/kg/min after unilateral moderate left external iliac artery stenosis.

Results: Before CPSD, PMP decreased significantly (P < .05) under adenosine stress compared with resting conditions, with right mTT of 7.5 seconds ± 3.6 versus 16.9 seconds ± 11.9 and WiR of 63.1 arbitrary units (AU) ± 49.0 versus 25.0 AU ± 17.5 and left mTT of 29.2 seconds ± 18.0 versus 56.3 seconds ± 38.7 and WiR of 13.6 AU ± 8.4 versus 6.0 AU ± 4.1. After CPSD, PMP did not differ significantly (P > .05) between conditions of adenosine stress and rest, with right mTT of 19.9 seconds ± 24.7 versus 23.2 seconds ± 21.0 and WiR of 16.2 AU ± 25.0 versus 20.5 AU ± 19.7 and left mTT of 23.3 seconds ± 23.1 versus 25.8 seconds ± 21.7 and WiR of 12.5 AU ± 6.2 versus 20.0 AU ± 12.1.

Conclusions: CPSD reduced peripheral artery sympathetic tone and may be an alternative to surgical or computed tomography-guided sympathectomy for the treatment of end-stage peripheral artery disease and Raynaud phenomenon.
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http://dx.doi.org/10.1016/j.jvir.2015.06.013DOI Listing
September 2015

Surfaceome of classical Hodgkin and non-Hodgkin lymphoma.

Proteomics Clin Appl 2015 Aug;9(7-8):661-70

Department of Biology, Institute of Molecular Systems Biology, Swiss Federal Institute of Technology (ETH) Zurich, Zurich, Switzerland.

Purpose: Classical Hodgkin lymphoma (cHL) is characterized by a low percentage of tumor cells in a background of diverse, reactive immune cells. cHL cells commonly derive from preapoptotic germinal-center B cells and are characterized by the loss of B-cell markers and the varying expression of other hematopoietic lineage markers. This phenotypic variability and the scarcity of currently available cHL-specific cell surface markers can prevent clear distinction of cHL from related lymphomas.

Experimental Design: We applied the cell surface capture technology to directly measure the pool of cell surface exposed proteins in four cHL and four non-Hodgkin lymphoma (NHL) cell lines.

Results: More than 1000 membrane proteins, including 178 cluster of differentiation annotated proteins, were identified and allowed the generation of lymphoma surfaceome maps. The functional properties of identified cell surface proteins enable, but also limit the information exchange of lymphoma cells with their microenvironment.

Conclusion And Clinical Relevance: Selected candidate proteins with potential diagnostic value were evaluated on a tissue microarray (TMA). Primary lymphoma tissues of 126 different B cell-derived lymphoma cases were included in the TMA analysis. The TMA analysis indicated gamma-glutamyltranspeptidase 1 as a potential additional marker that can be included in a panel of markers for differential diagnosis of cHL versus NHL.
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http://dx.doi.org/10.1002/prca.201400146DOI Listing
August 2015

Accumulation of ALDH1-positive cells after neoadjuvant chemotherapy predicts treatment resistance and prognosticates poor outcome in ovarian cancer.

Oncotarget 2015 Jun;6(18):16437-48

Department of Obstetrics and Gynecology, Center for Integrated Oncology, University of Bonn, Sigmund-Freud-Strasse, Bonn, Germany.

Although ovarian cancer is a highly chemosensitive disease, it is only infrequently cured. One of the major reasons lies in the presence of drug-resistant cancer stem-like cells, sufficient to fuel recurrence. We phenotyped cancer stem-like cells by flow cytometry and immunohistochemistry in 55 matched samples before and after taxane/platinum-based neoadjuvant chemotherapy. All used markers of stemness (ALDH1, CD24, CD117, CD133) isolated low frequencies of malignant cells. ALDH1 was the most valuable marker for tracking stemness in vivo. The enrichment of ALDH1 expression after treatment was associated with a poor response to chemotherapy, with platinum resistance and independently prognosticated unfavorable outcome. Our results suggest that increased ALDH1 expression after treatment identifies patients with aggressive tumor phenotypes.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4599280PMC
http://dx.doi.org/10.18632/oncotarget.4103DOI Listing
June 2015

HIPEC ROC I: a phase I study of cisplatin administered as hyperthermic intraoperative intraperitoneal chemoperfusion followed by postoperative intravenous platinum-based chemotherapy in patients with platinum-sensitive recurrent epithelial ovarian cancer.

Int J Cancer 2015 Feb 17;136(3):699-708. Epub 2014 Jun 17.

Department of Obstetrics and Gynecology, University Hospital Bonn, Bonn, Germany; Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, NY, USA; Center for Integrated Oncology Cologne Bonn, University Hospitals Cologne and Bonn, Bonn, Germany.

This phase I study tested the safety, feasibility, pharmacokinetics and pharmacodynamics of cisplatin administered as hyperthermic intraoperative intraperitoneal chemoperfusion (HIPEC) in patients with platinum-sensitive recurrent epithelial ovarian cancer (EOC) undergoing secondary cytoreductive surgery followed by postoperative platinum-based intravenous chemotherapy. Twelve patients with operable, recurrent platinum-sensitive EOC (recurrence ≥6 months after first-line therapy) were included according to the classical 3+3 dose-escalation design at three dose levels-60, 80 and 100 mg/m(2). After surgical cytoreduction, a single dose of cisplatin was administered via HIPEC for 90 min at 41-43°C. Postoperatively, all patients were treated with standard intravenous platinum-based combination chemotherapy. One of six patients experienced a dose-limiting toxicity (grade 3 renal toxicity) at a dose of 100 mg/m(2). The remaining five patients treated with 100 mg/m(2) tolerated their treatment well. The recommended phase II dose was established at 100 mg/m(2). The mean peritoneal-to-plasma AUC ratio was 19·5 at the highest dose level. Cisplatin-induced DNA adducts were confirmed in tumor samples. Common postoperative grade 1-3 toxicities included fatigue, postoperative pain, nausea, and surgical site infection. The ability to administer standard intravenous platinum-based chemotherapy after HIPEC was uncompromised. Cisplatin administered as HIPEC at a dose of 100 mg/m(2) has an acceptable safety profile in selected patients undergoing secondary cytoreductive surgery for platinum-sensitive recurrent EOC. Favorable pharmacokinetic and pharmacodynamic properties of HIPEC with cisplatin were confirmed at all dose levels, especially at 100 mg/m(2). The results are encouraging to determine the efficacy of HIPEC as a complementary treatment in patients with EOC.
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http://dx.doi.org/10.1002/ijc.29011DOI Listing
February 2015

Loss of anterior gradient-2 expression is an independent prognostic factor in colorectal carcinomas.

Eur J Cancer 2014 Jul 30;50(10):1722-1730. Epub 2014 Apr 30.

Institute of Pathology, University Hospital Bonn, Germany. Electronic address:

Aims: The human Anterior Gradient-2 (AGR2) protein is strongly expressed in various human cancers, and it has been described to promote aggressive tumour features in some entities. So far, a comprehensive analysis of AGR2 expression in colorectal carcinomas has not been described.

Methods: Normal intestinal cells and colorectal carcinoma cell lines were analysed for AGR2 expression. AGR2 protein expression was immunohistochemically analysed in 28 normal tissue samples and 1068 tissue samples of clinically well characterised colorectal carcinomas. For statistical analysis, chi square test, spearman rank correlations, Kaplan-Meier estimates (Log rank test) and Cox regression were applied to test for diagnostic or prognostic associations.

Results: In the normal intestinal cell line and in normal colon mucosa AGR2 was found in all cases (n=28). In contrast, loss of AGR2 was found in all six analysed colorectal cancer cell lines and in 833/1068 (78%) of the colorectal carcinoma tissue samples analysed, and it was significantly associated with a higher tumour grade and tumour localisation in the left-sided colon. In addition to the conventional prognostic tumour parameters pT category, nodal status, metastasis and histological tumour grade the loss of AGR2 expression was significantly associated with reduced overall survival times in univariate and multivariate analyses, thus suggesting AGR2 as an independent prognostic factor in primary colorectal carcinoma.

Conclusions: AGR2 is frequently lost in colorectal carcinomas and might be a novel independent prognostic factor for overall patient survival.
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http://dx.doi.org/10.1016/j.ejca.2014.04.012DOI Listing
July 2014

Paraneoplastic disseminated intravascular coagulation caused by splenic littoral cell angioma.

Ann Hematol 2014 Oct 29;93(10):1795-6. Epub 2014 Mar 29.

Medical Clinic III for Oncology, Haematology and Rheumatology, University Hospital Bonn (UKB), Sigmund-Freud-Straße 25, 53127, Bonn, Germany.

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http://dx.doi.org/10.1007/s00277-014-2060-xDOI Listing
October 2014

The combined expression of the stromal markers fibronectin and SPARC improves the prediction of survival in diffuse large B-cell lymphoma.

Exp Hematol Oncol 2013 Oct 8;2(1):27. Epub 2013 Oct 8.

Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland.

Background: In diffuse large B-cell lymphomas, gene expression profiling studies attributed a major biologic role to non-neoplastic cells of the tumour microenvironment as its composition and characteristics were shown to predict survival. In particular, the expression of selected genes encoding components of the extracellular matrix was reported to be associated with clinical outcome. Nevertheless, the translation of these data into robust, routinely applicable immunohistochemical markers is still warranted. Therefore, in this study, we analysed the combination of the expression of the extracellular matrix components Fibronectin and SPARC on formalin-fixed paraffin embedded tissue derived from 173 patients with DLBCL in order to recapitulate gene expression profiling data.

Results: The expression of Fibronectin and SPARC was detected in 77/173 (44.5%) and 125/173 (72.3%) cases, respectively, and 55/173 (31.8%) cases were double positive. Patients with lymphomas expressing Fibronectin showed significantly longer overall survival when compared to negative ones (6.3 versus 3.6 years). Moreover, patients with double positive lymphomas also presented with significantly longer overall survival when compared with the remaining cases (11.6 versus 3.6 years) and this combined expression of both markers results in a better association with overall survival data than the expression of SPARC or Fibronectin taken separately (Hazard ratio 0.41, 95% confidence interval 0.17 to 0.95, p = 0.037). Finally, neither Fibronectin nor SPARC expression was associated with any of the collected clinico-pathological parameters.

Conclusions: The combined immunohistochemical assessment of Fibronectin and SPARC, two components of the extracellular matrix, represents an important tool for the prediction of survival in diffuse large B-cell lymphomas. Our study suggests that translation of gene expression profiling data on tumour microenvironment into routinely applicable immunohistochemical markers is a useful approach for a further characterization of this heterogeneous type of lymphoma.
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http://dx.doi.org/10.1186/2162-3619-2-27DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3852975PMC
October 2013

The impact of pulmonary bone component embolism: an autopsy study.

J Clin Pathol 2014 Apr 7;67(4):370-4. Epub 2014 Jan 7.

Institute of Pathology Liestal, Cantonal Hospital Baselland, , Liestal, Switzerland.

Aims: Pulmonary bone marrow embolism (BME) and pulmonary bone fragment embolism (BFE) are two types of non-thrombotic pulmonary embolism (NTPE). While BME can be found consistently in autopsies, BFE is a rarely observed event. Both these conditions have bone lesions as source of embolism and are not considered to be causative for death.

Methods: A retrospective autopsy study was performed and lung whole tissue slides were reviewed for the presence of pulmonary embolism. Clinicopathological data were screened for osseous lesions considered as risk factors for BME and BFE.

Results: We reviewed 985 consecutive, unselected autopsies and identified 29 cases of BME (2.9%) and 5 cases of BFE (0.5%). Both conditions were mutually exclusive. While BME showed a significant association with costal fractures, BFE was significantly associated with osteomyelitis and previously performed femur nailing. There were between 1 and 346 bone emboli in BFE with a density ranging from 0.74 to 30.5 emboli/cm(2) with mean embolic diameter of 45.8±37.6 μm. In two patients, BFE contributed significantly to fatal outcome.

Conclusions: BME was associated with costal fractures, while BFE was associated with orthopaedic procedures and osteomyelitis. BFE can result in patient death. Both conditions appeared exclusively, indicating that although they originate from osseous lesions their underlying pathogenesis may likely be different.
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http://dx.doi.org/10.1136/jclinpath-2013-202056DOI Listing
April 2014

Computed tomography perfusion imaging of renal cell carcinoma: systematic comparison with histopathological angiogenic and prognostic markers.

Invest Radiol 2013 Apr;48(4):183-91

Institute of Diagnostic and Interventional Radiology, University Hospital Zurich, Zurich, Switzerland.

Purpose: The aim of this study was to systematically analyze the correlation between computed tomography (CT) perfusion and histopathological angiogenic and prognostic markers in patients with renal cell carcinoma (RCC).

Material And Methods: Fifteen patients (12 men; mean age, 64.5 ± 9.4 years) with RCC underwent contrast-enhanced CT perfusion imaging (scan range, 10 cm; scan time, 40 seconds; dual-source 128-section CT) 1 day before surgery. The procedure for surgical specimen processing was modified to obtain an exact match with CT images. Microvessel density (MVD) was quantified by CD34 staining, and lymphatic vessel density (LVD) was stained with D2-40 antibodies. The CT perfusion values blood flow (BF), blood volume (BV), and flow extraction product (K(Trans)) were calculated using the maximum-slope and a delay-corrected modified Patlak approach and were correlated to MVD and LVD. The relationship between CT perfusion and the prognostic markers pT stage, Fuhrman grade, and tumor necrosis was evaluated.

Results: Histopathology revealed varying high MVD but low or absent intratumoral LVD. The BF and BV of RCC, both including and excluding necrotic regions, showed significant correlations with MVD (r = 0.600-0.829, P < 0.05 each). Significant correlations between MVD and K(Trans) were found only in small tumor areas exhibiting no necrosis (r = 0.550, P < 0.05). No significant correlation was found between BF, BV, and K(Trans) with intratumoral LVD (P = 0.35-0.82). With higher pT stage and Fuhrman grade, BF, BV, and K(Trans) were lower, similar to the MVD, but without reaching statistical significance. Blood flow, BV, and K(Trans) were significantly higher in RCCs with less than 50% necrosis than in those with 50% or grater necrosis (P < 0.05 each).

Conclusion: Our study indicates that BF and BV from CT perfusion reflect blood vessels of RCC. Computed tompgraphic perfusion parameters differ significantly depending upon the degree of tumor necrosis.
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http://dx.doi.org/10.1097/RLI.0b013e31827c63a3DOI Listing
April 2013

Smoothelin is a specific and robust marker for distinction of muscularis propria and muscularis mucosae in the gastrointestinal tract.

Histopathology 2010 Aug;57(2):244-9

Institut für Klinische Pathologie, UniversitätsSpital Zürich, Schmelzbergstrasse 12, Zürich, Switzerland.

Aims: As tumour specimens and biopsy specimens become smaller, recognition of anatomical structures relevant for staging is increasingly challenging. So far no marker is known that reliably discriminates between muscularis propria (MP) and muscularis mucosae (MM) of the gastrointestinal tract. Recently, smoothelin expression has been shown to differ in MP and MM of the urinary bladder. We aimed to analyse the expression of smoothelin in the gastrointestinal tract in MP and MM in order to define a novel diagnostic tool to identify MM bundles.

Methods And Results: The expression of smoothelin was analysed immunohistochemically in comparison with alpha-smooth muscle actin (alpha-SMA) in specimens from colon, stomach and oesophagus (n = 107). In contrast to alpha-SMA, which equally stained MM and MP, absent or significantly weaker smoothelin expression was found in MM was found, which was particularly valid in colon and gastric specimens.

Conclusions: The combination of smoothelin and SMA represents a robust marker to discriminate MM from MP in the gastrointestinal tract.
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http://dx.doi.org/10.1111/j.1365-2559.2010.03618.xDOI Listing
August 2010

Impact of using elastic stains for detection of venous invasion in the prognosis of patients with lymph node negative colorectal cancer.

Int J Colorectal Dis 2010 Jun 9;25(6):741-6. Epub 2010 Feb 9.

Cantonal Institute for Pathology, Cantonal Hospital Liestal, Mühlemattstrasse 11, 4410 Liestal, Switzerland.

Purpose And Methods: Patients with nodal negative colorectal cancer (CRC) suffer recurrent or metastatic disease in 40% of cases after surgical resection. To investigate a potential prognostic impact of vascular tumor infiltration, we retrospectively analyzed 185 nodal negative stage I and II CRC specimens for the presence of intra- and/or extramural venous invasion (V1IM/V1EM) using elastic stains of all tumor sections and correlated our findings with the clinical follow-up.

Results: Venous invasion was observed in 43 (23.2%) patients by elastic stains compared with six (3.2%) using HE only (p < 0.05). Venous invasion was more common in stage II than in stage I tumors (28.1% versus 5.1%; p < 0.05). However, survival analyses showed no significant differences in 5-year survival rates comparing patients with and without venous invasion (68% and 71%, p = 0.543) or patients with V1IM and V1EM (62% vs. 74%, p = 0.473), respectively.

Conclusions: Our data emphasize the need for standardized criteria, including elastic stains, to reliably detect vascular invasion in CRC. Doing so, however, the prognostic impact of venous invasion in stage I and II CRC may be lower as previously anticipated.
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http://dx.doi.org/10.1007/s00384-010-0890-0DOI Listing
June 2010

Patients with low prostate-specific antigen levels (< or =4 ng/ml) would benefit from a twelve-core biopsy protocol for prostate cancer detection.

Urol Int 2007 ;78(4):318-22

Kantonales Institut fur Pathologie, Liestal, Schweiz.

Introduction: Prostate biopsy protocols using twelve cores rather than the standard six cores have consistently shown improved prostate cancer detection rates. The aim of our study was to evaluate whether the improved rate of prostate cancer detection in patients with low prostate-specific antigen levels warrants the standardization of a twelve-core biopsy protocol in this group.

Patients And Methods: The clinical and pathological records from 241 patients treated between 2000 and 2003 were evaluated, and the impact of a twelve-core biopsy protocol on the prostate cancer detection rate relative to prostate-specific antigen levels compared to the standardized six-core biopsies was analyzed.

Results: Prostate cancer was detected in 34% (81/241) of the patients who underwent transrectal ultrasound-guided biopsy. An additional 23.5% (19/81) of the carcinomas were diagnosed using the twelve-core biopsy protocol, and 84.2% (16/19) of these fulfilled the clinical significance criterion developed by Epstein and coworkers (see text). Interestingly, the greatest increase was found in the patient group with prostate-specific antigen levels < or =4 ng/ml.

Conclusions: Patients with low prostate-specific antigen levels (< or =4 ng/ml) would benefit from the standardized use of a twelve-core biopsy protocol using peripheral cores.
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http://dx.doi.org/10.1159/000100835DOI Listing
June 2007