Wolfsburg, Germany
Wolfsburg, Germany

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Stollberger C.,Krankenanstalt Rudolfstiftung | Gerecke B.,Klinikum Wolfsburg | Engberding R.,Klinikum Wolfsburg | Grabner B.,Krankenanstalt Rudolfstiftung | And 4 more authors.
JACC: Cardiovascular Imaging | Year: 2015

Objectives The aim of the study was to assess interobserver agreement (IOA) between 3 observers from 2 laboratories. Background IOA of left ventricular hypertrabeculation/noncompaction (LVHT) in adults has only been studied within single echocardiographic laboratories. Methods Echocardiographic recordings with and without LVHT were selected and anonymized. The "not-LVHT" cases were matched for age and systolic function. Each observer reviewed the recordings, blinded to the initial diagnosis and the other observers' results. Pre-defined criteria for LVHT were: 1) >3 prominent trabeculae at end-diastole, distinct from papillary muscles, false tendons, or aberrant bands; 2) a noncompacted part of a 2-layered myocardial structure formed by these trabeculations; 3) a ratio of >2:1 of noncompacted to compacted layer at end-systole; and 4) perfusion of the intertrabecular spaces from the ventricular cavity. IOA was estimated using the kappa measure of concordance. Results Cine-loops of 100 patients (42 women, ages 16 to 92 years), 50 from each center, and 51 with LVHT as the initial diagnosis, were reviewed. The left ventricular end-diastolic diameter was 32 to 78 mm, and ejection fraction, 4% to 88%. The observers agreed about presence (n = 29) or absence (n = 36) of LVHT and disagreed in 35 cases. Agreement was higher among the 2 observers from the same laboratory (kappa 0.793 [95% confidence interval (CI): 0.672 to 0.915]) than from different laboratories (kappa 0.628 [95% CI: 0.472 to 0.784], kappa 0.669 [95% CI: 0.521 to 0.818]). The observers agreed with the initial report of LVHT-presence in 53% and of absence in 67%. By reviewing the discordant cases, consensus was achieved about LVHT presence (n = 8) or absence (n = 16); in 11 cases, the diagnosis remained questionable. Discordance was due to poor image quality, lack of views in different apical planes, aberrant bands and chordae tendineae, abnormally sized or inserting papillary muscles, and localized calcifications of the endocardium. Conclusions IOA was substantial for diagnosing LVHT. However, even the application of pre-defined criteria yielded disagreement in 35% of cases; and after mutual review, there were still 11% questionable cases. © 2015 American College of Cardiology Foundation.


Lorenzen S.,TU Munich | Thuss-Patience P.,Charité - Medical University of Berlin | Al-Batran S.E.,UCT | Lordick F.,University of Leipzig | And 7 more authors.
Annals of Oncology | Year: 2013

Background: The aim of this study was to evaluate the impact of pathologic complete response (pCR) on outcome in patients with gastric or esophagogastric junction (EGJ) adenocarcinoma after neoadjuvant docetaxel/platin/fluoropyrimidine-based chemotherapy.Patients and methods: Patients received at least one cycle of chemotherapy for potentially operable disease.Pretreatment clinicopathologic factors and pCR were investigated. Disease-free survival (DFS), overall survival (OS) and tumor-related death were correlated with pCR.Results: One hundred twenty patients were included in this analysis. Eighteen patients (15%) achieved a pCR. Tumor localization in the EGJ was identified as the only significant predictor of pCR (P = 0.019). Median follow-up was 41.1 months. Median DFS and OS for all patients were 24.1 and 48.6 months, respectively. Median DFS for patients with a pCR was not reached versus 22.1 months non-pCR patients (hazard ratio, HR 0.38; 3-year DFS: 71.8% and 37.7%,respectively, P = 0.018). While OS was not significantly different, the risk for tumor-related death was significantly lower for pCR patients compared with non-pCR patients (3-year cumulative incidences of 6.4% and 45.4%, respectively, P=0.009). Conclusion: A pCR following preoperative docetaxel/platin/fluoropyrimidine indicates favorable outcome in patients with gastric or EGJ adenocarcinoma. Tumor location in the EGJ is associated with a higher pCR rate. © The Author 2013. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.


Petry K.U.,Klinikum Wolfsburg
Scandinavian Journal of Clinical and Laboratory Investigation | Year: 2014

In recent analyses of the global burden of cancer among women, cervical cancer ranked second to breast cancer. Numbers of new cervical cancer cases are increasing constantly although this tumor is one of the best preventable malignancies of all relevant human cancers. The genesis of cervical cancer depends essentially on an infection of the uterine cervix with human papillomavirus (HPV) that needs to persist for many years and decades. Oncogenic cell transformation occurs almost exclusively in a discrete cell population at the squamous columnar junction (SCJ). These peculiarities enable primary prevention with HPV-vaccination as well as secondary prevention by detecting and treating true precursor lesions. The actual screening program with annual cytology smears is already effective but results in a high number of false positive results and unnecessary treatments. Based on a good understanding of the etiology and high evidence from large randomized controlled trials a significant improvement in the prevention of cervical cancer by shifting to HPV screening in women aged 30 years or older is feasible. This would result in a further reduction of new cancer cases by 70-80 % with less screening examinations and interventions when well-defined patient pathways are followed and colposcopy in accordance with international quality standards is used as the gold standard for the minimal invasive management of abnormal findings. HPV vaccination prevents the development of approximately 80 % of true precursors and should have a similar impact on the incidence of cervical cancer. A combination of HPV vaccination and screening could almost eradicate cervical cancer and reduce the burden of other tumors and diseases related to HPV. © 2014 Informa Healthcare.


Petry K.U.,Klinikum Wolfsburg
Best Practice and Research: Clinical Obstetrics and Gynaecology | Year: 2011

Management of cervical intraepithelial neoplasia (CIN) needs to protect women at risk from developing cervical cancer and to avoid over-treatment as well as obstetrical complications in women undergoing invasive treatment. Strong evidence shows that CIN3 is a true precursor and must be treated, whereas CIN1 lesions do not benefit from immediate surgery and should be followed conservatively. Although the clinical course of CIN2 differs fromCIN3, it should be treated the sameway for legal reasons. Colposcopy plays a central role in selection of patients and treatments. Treatment of CIN2 and 3 should be excisional. Large loop excision of the transformation zone, high-frequency- needle or laser conisation are equally good, whereas cold-knife conisation is associated with an excess risk for subsequent obstetrical complications. Human papillomavirus testing and cytologyat 6months seems to be the best post-treatmentmonitoring, although this needs to be confirmed by randomised-controlled trials. Future research needs to focus more on howthe quality of colposcopy and the overall management concept determines the clinical outcome instead of exploring the role of single technical methods. Furthermore, it seems to be necessary to evaluate the best management of CIN2 in young and in vaccinated women. © 2011 Elsevier Ltd. All rights reserved.


Petry K.U.,Klinikum Wolfsburg | Luyten A.,Klinikum Wolfsburg | Scherbring S.,Klinikum Wolfsburg
Gynecologic Oncology | Year: 2013

Objective: Combining HPV and Pap screening achieves very good risk stratification and sensitive detection of CIN3 and cancer (CIN3 +), but poorer specificity, and may result in an increased risk of glandular and new lesions during follow-up. We examined if this phenomenon may compromise the accuracy of colposcopy. Methods: As part of a primary HPV screening pilot project comprising 19,624 participants aged over 30 years, the failure rate to detect CIN3 at first visit was measured over a five-year period to assess the quality of colposcopy as an overall management concept. Management relied on excisional biopsies in all HSIL cytology or major findings on colposcopy, endocervical assessment in type 3 transformation zones (TZ) and guided biopsies in type 1 or 2 TZ. Results: Of 667 women referred for colposcopy because of atypical Pap smears and/or HPV persistency, 171 were diagnosed with CIN3+. All 18 cancers and 140/153 CIN3 cases were diagnosed at the first visit. Of 13 CIN3 observed during follow-up, five were classified as new cases, five as definite and three as probably colposcopy failures, giving a failure rate of 4.7% (8/171). Only three failures were related to false-negative punch biopsies while five occurred because of false-negative endocervical assessment in type 3 TZ. Conclusions: Colposcopy management following defined pathways was safe in this HPV screening program with an acceptable failure rate. Further improvements may depend on developing better methods for endocervical assessment rather than for ectocervical biopsies. © 2012 Elsevier Inc. All rights reserved.


Lorenzen S.,TU Munich | Pauligk C.,UCT | Homann N.,Klinikum Wolfsburg | Schmalenberg H.,University Hospital Jena | And 2 more authors.
British Journal of Cancer | Year: 2013

Background: The aim of this exploratory subgroup analysis of the fluorouracil, oxaliplatin, docetaxel (FLOT)65+ trial was to determine tolerability and feasibility of perioperative chemotherapy in elderly, potentially operable esophagogastric cancer patients. Methods: Patients aged ≥65 with locally advanced esophagogastric adenocarcinoma were randomized to perioperative chemotherapy consisting of four pre-and four postoperative cycles of infusional 5-FU, leucovorin, and oxaliplatin (FLO) without or with docetaxel 50 mg m-2 (FLOT), every 2 weeks. Results: Forty-four patients with a median age of 70 years were randomized and 43 patients started preoperative chemotherapy (FLO, 22; FLOT, 21). Thirty-eight (86.4%) patients completed four cycles of preoperative chemotherapy and 32 (74.4%) proceeded to surgery, with 67.4% R0 resections on intent-to-treat analysis (90.1% of the 32 patients who underwent resection). Median overall survival was not reached and median progression-free survival (PFS) was 17.3 months. Compared with the FLO group, the FLOT group showed a trend towards an improved median PFS (21.1 vs 12.0 months; P=0.09), however, associated with increased chemotherapy related toxicity. No perioperative mortality was observed. Postoperative morbidity was observed in 46.9% of patients (FLO, 35.3%; FLOT, 60%). Conclusion: Neoadjuvant FLO or FLOT may offer a reasonable chance of curative surgery in elderly patients with locally advanced resectable gastroesophageal cancer. However, the increase in side effects with the FLOT regimen and postoperative morbidity should be carefully considered when an intensive chemotherapy regimen is planned. © 2013 Cancer Research UK. All rights reserved.


Luyten A.,Klinikum Wolfsburg | Sorgel P.,Medizinische Hochschule Hanover | Clad A.,University Hospital Freiburg | Gieseking F.,Universitatsklinik Hamburg Eppendorf | And 5 more authors.
Journal of the American Academy of Dermatology | Year: 2014

Background: Extramammary Paget disease (EMPD) is a very rare genital neoplasia associated with a high frequency of local recurrences. Surgical excision is the standard treatment, but results in mutilating procedures in patients with advanced or recurrent disease. Case reports have shown clinical responses to imiquimod in patients with EMPD, but this therapy has not been evaluated systematically. Objective: The aim of this study was to evaluate imiquimod as local treatment of first-time and recurrent EMPD. Methods: All cases of biopsy-proven EMPD of the vulva treated within the German Colposcopy Network or other institutions specializing in vulvar diseases in Germany were included in this retrospective analysis. Results: A total of 21 women with EMPD treated with imiquimod were identified: 11 (52.4%) achieved complete response, 6 (28.6%) achieved partial response, and there were no cases of progressive disease. The dose and duration of imiquimod differed between patients. The mean duration of treatment exceeded 16 weeks in women achieving complete response. Limitations: EMPD is rare and this retrospective study is limited by the small number of patients identified. Conclusion: When associated cancers and invasive growth are excluded, imiquimod appears to be a useful treatment option for recurrent EMPD and may avoid extensive mutilating surgical treatment. © 2013 by the American Academy of Dermatology, Inc.


Petry K.U.,Klinikum Wolfsburg
Monographs in Virology | Year: 2012

Approximately 70% of all cancers of the vagina and 40% of vulval cancers are associated with high grade human papillomavirus (HPV). The corresponding prevalence in vulval intraepithelial neoplasia (VIN) 2/3 and vaginal intraepithelial neoplasia (VAIN) 2/3 lesions is in the range of 85-95%. While there is no efficient screening for these neoplasms in the general population, risk groups such as immunocompromised women and patients with a history of cervical intraepithelial neoplasia may benefit from colposcopy follow-up. Frank invasive cancers are a clinical diagnosis but most preinvasive lesions are diagnosed by colposcopy with biopsies. There are two distinct entities of VIN and squamous cell cancer of the vulva. HPV is linked to the common undifferentiated VIN and basaloid cancers while the rare differentiated VIN and the keratinizing cancers are HPV-negative. Lichen sclerosus seems to play a role in the genesis of these tumors. Surgery is the treatment of choice for preinvasive and early tumors, although application of imiquimod is another option for VIN2/3. Copyright © 2012 S. Karger AG, Basel.


Petry K.U.,Klinikum Wolfsburg
Monographs in Virology | Year: 2012

There is a high level of evidence coming from large randomized controlled trials that primary human papillomavirus (HPV) screening is better than cytology in detecting cervical intraepithelial neoplasia type 3 and cervical cancer as well as in reducing the incidence of and the mortality from cervical cancer. However, HPV screening will only be beneficial and cost-efficient in women above 30 years and only in well-structured programs with longer screening intervals. Pilot projects in the USA and Germany show that HPV screening is feasible even on local or regional levels with similar efficiency as observed in randomized controlled trials. The single remaining serious argument against screening with HPV testing, i.e. the missing algorithm for women with normal cytology who tested positive for HPV, may be solved by a triage using p16/Ki67-stained cytology. Copyright © 2012 S. Karger AG, Basel.


Petry K.U.,Klinikum Wolfsburg | Luyten A.,Klinikum Wolfsburg | Justus A.,Conreso GmbH. Klinische Forschung | Iftner A.,University Hospital of Tuebingen | And 3 more authors.
BMC Infectious Diseases | Year: 2012

Background: Wolfsburg HPV Epidemiological Study (WOLVES) is a population-based cohort study on HPV infections and associated diseases in the pre-vaccination era in young women in Wolfsburg, Germany.Methods: Women born 1983/84 or 1988/89 were invited to participate. Participants were recruited in gynecology practices, and completed a questionnaire with socioeconomic, sexual and medical data including vaccination status. Pelvic examination with Pap smear and HPV testing (HC2 = Hybrid Capture 2) was obligatory. HC2-positive and 10% of HC2-negative samples were tested for specific HPV types with SPF-10-PCR, and in inconclusive cases with DNA sequencing. Women with genital warts (GW) and those with atypical Pap smears were transferred for colposcopy. GWs were classified as typical condylomata acuminata (TCA), flat condyloma (FC) and seborrheic wart-like (SWL).Results: In total, 1258 subjects were recruited from the target population of 2850 (44.1%). Overall the prevalence of HC2 low-risk (LR) types was 8.5%. HPV6 was the most frequent LR type (2.1%), followed by HPV42 (1.1%), HPV11 and HPV44 (each 0.4%). LiPA showed a low sensitivity for HPV types 42, 90 and 91, which were detected only by HC2 and HPV sequencing. Nine women (0.7%) were transferred with incident GW: five TCA, two FC and two SWL. All TCA were associated with HPV6 in corresponding cervical swabs and warts. Tissues of SWL contained HPV6 (n = 1) and HPV16 (n = 1). The cumulative life-risk for GW was 1.4% in the 1988/89 and 4.8% in the 1983/84 cohort. Eight of 107 HC2-LR + and five of nine cases of GW had concomitant abnormal Pap smears. All CIN lesions could be linked to high-risk HPV types but borderline and low-grade abnormal smears were explained by vaginal and cervical TCA in four cases.Conclusions: HC2 was a specific test for the detection of established and potential LR types. In this first WOLVES analysis, HPV6 was the most frequent HPV type and the single LR type linked to disease. The observed GW incidence of 715 per 100,000 fits well with estimates of healthcare providers. Although life risks for GW were lower than in Scandinavian analyses, the societal burden within the WOLVES populations was considerable. © 2012 Petry et al.; licensee BioMed Central Ltd.

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