Johann Hauss
Leipzig University
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Annals of Surgery | 1998
Matthias W. Lorenz; Hans-Helge Müller; Harald Schramm; Heinz-Jochen Gassel; Hans-Günther Rau; Karsten Ridwelski; Johann Hauss; Rudolf Stieger; Karl-Walter Jauch; Wolf O. Bechstein; Albrecht Encke
OBJECTIVE To determine the impact of adjuvant hepatic arterial infusion (HAI) on survival relative to resection alone in patients with radical resection of colorectal liver metastases. SUMMARY BACKGROUND DATA Nearly 40% to 50% of all patients with colorectal carcinoma develop liver metastases. Curative resection results in a 5-year survival rate of 25% to 30%. Intrahepatic recurrence occurs after a median of 9 to 12 months in up to 60% of patients. The authors hypothesized that adjuvant intraarterial infusion of 5-fluorouracil (5-FU) might decrease the rate of intrahepatic recurrence and improve survival in patients with radical resection of colorectal liver metastases. METHODS Between April 5, 1991, and December 31, 1996, patients with colorectal liver metastases from 26 hospitals were stratified by the number of metastases and the site of the primary tumor and randomized to resection of the liver metastases followed by adjuvant HAI of 5-FU (1000 mg/m2 per day for 5 days as a continuous 24-hour infusion) plus folinic acid (200 mg/m2 per day for 5 days as a short infusion), or liver resection only. RESULTS The first planned intention-to-treat interim analysis after inclusion of 226 patients and 91 events (deaths) showed a median survival of 34.5 months for patients with adjuvant therapy versus 40.8 months for control patients. The median time to progression was 14.2 months for the chemotherapy group versus 13.7 months for the control group. Grade 3 and 4 toxicities (World Health Organization), mainly stomatitis (57.6%) and nausea (55.4%), occurred in 25.6% of cycles and 62.9% of patients. CONCLUSION According to this planned interim analysis, adjuvant HAI, when used in this dose and schedule in patients with resection of colorectal liver metastases, reduced the risk of death at best by 15%, but at worst the risk of death was doubled. Thus, the chance of detecting an expected 50% improvement in survival by the use of HAI was only 5%. Patient accrual was therefore terminated.
Annals of Surgery | 2006
Helmut Witzigmann; Frieder Berr; Ulrike Ringel; Karel Caca; Dirk Uhlmann; Konrad Schoppmeyer; Andrea Tannapfel; Christian Wittekind; Joachim Mössner; Johann Hauss; Marcus Wiedmann
Objective:First, to analyze the strategy for 184 patients with hilar cholangiocarcinoma seen and treated at a single interdisciplinary hepatobiliary center during a 10-year period. Second, to compare long-term outcome in patients undergoing surgical or palliative treatment, and third to evaluate the role of photodynamic therapy in this concept. Summary Background Data:Tumor resection is attainable in a minority of patients (<30%). When resection is not possible, radiotherapy and/or chemotherapy have been found to be an ineffective palliative option. Recently, photodynamic therapy (PDT) has been evaluated as a palliative and neoadjuvant modality. Methods:Treatment and outcome data of 184 patients with hilar cholangiocarcinoma were analyzed prospectively between 1994 and 2004. Sixty patients underwent resection (8 after neoadjuvant PDT); 68 had PDT in addition to stenting and 56 had stenting alone. Results:The 30-day death rate after resection was 8.3%. Major complications occurred in 52%. The overall 1-, 3-, and 5-year survival rates were 69%, 30%, and 22%, respectively. R0, R1, and R2 resection resulted in 5-year survival rates of 27%, 10%, and 0%, respectively. Multivariate analysis identified R0 resection (P < 0.01), grading (P < 0.05), and on the limit to significance venous invasion (P = 0.06) as independent prognostic factors for survival. PDT and stenting resulted in longer median survival (12 vs. 6.4 months, P < 0.01), lower serum bilirubin levels (P < 0.05), and higher Karnofsky performance status (P < 0.01) as compared with stenting alone. Median survival after PDT and stenting, but not after stenting alone, did not differ from that after both R1 and R2 resection. Conclusion:Only complete tumor resection, including hepatic resection, enables long-term survival for patients with hilar cholangiocarcinoma. Palliative PDT and subsequent stenting resulted in longer survival than stenting alone and has a similar survival time compared with incomplete R1 and R2 resection. However, these improvements in palliative treatment by PDT will not change the concept of an aggressive resectional approach.
British Journal of Cancer | 2009
Susanne Singer; Susanne Kuhnt; Heide Götze; Johann Hauss; Andreas Hinz; A Liebmann; O. Krauß; Lehmann A; Reinhold Schwarz
The aim of this study was to determine optimal cutoff scores for the Hospital Anxiety and Depression Scale (HADS) when used in evaluating cancer patients in acute care. A total of 689 cancer patients were assessed during their first days of in-patient treatment, using the structured clinical interview for DSM and the HADS. Statistical analysis was performed using ROC curves. A total of 222 patients (32%) had a mental disorder. The area under the curve was the best in the total scale of the HADS, namely 0.73. With a score of ⩾13, it is possible to detect 76% of the cases with a specificity of .60, whereas 95% of the cases can be detected with a score of ⩾6 (specificity 0.21). With scores of ⩾16 and ⩾22, recommended by the test authors for primary care, only 59 and 30% of the comorbid cancer patients are indicated. Lower HADS cutoff scores when preferable when evaluating cancer patients than are recommended for use in primary care. When using HADS in clinical practice and epidemiological studies, it is important to decide whether, for the task at hand, high detection rates of affected patients or low misclassification rates are more important.
The Journal of Pathology | 2003
Andrea Tannapfel; Kathrin Anhalt; Philip Häusermann; Florian Sommerer; Markus Benicke; Dirk Uhlmann; Helmut Witzigmann; Johann Hauss; Christian Wittekind
Characterization of the protein profiles expressed by hepatocellular carcinomas (HCCs) may identify the genes involved in hepatocellular carcinogenesis and offers the possibility of elucidating clinical biomarkers. In an effort to discover such proteins and pathways that are deregulated in hepatocellular carcinogenesis, cellular proteomes of matched normal liver cells and carcinoma were analysed by tissue microdissection and protein microarrays. Using protein microarrays made up of 83 different antibodies, it was possible to monitor alterations of the protein levels in HCC and non‐neoplastic liver tissue. Further analysis of altered proteins was performed using western blot analysis and tissue microarrays (TMAs) containing 210 HCC specimens and corresponding liver tissue. The protein microarray approach revealed differential expression between HCC and normal liver of 32 of the 83 proteins examined: 21 of these were up‐regulated and 11 down‐regulated. IGF (insulin growth factor) II, ADAM (a disintegrin and metalloproteases) 9, STAT (signal transducers and activators of transcription) 3, SOCS (suppressors of cytokine signalling) 3, and cyclin D1 were significantly up‐regulated and collagen I, SMAD 4, FHIT (fragile histidine triad), and SOCS1 were down‐regulated. The differential expression of these proteins was confirmed using western blot analysis and TMAs. Correlation of differentially regulated proteins with clinico‐pathological data showed that cyclin D1 and SOCS1 were associated with tumour prognosis in univariate analysis, but not multivariate analysis. These data indicate that the development of an array‐based approach for the determination of protein profiles in HCC may facilitate the identification of new proteins associated with carcinogenesis or prognosis. Copyright
BMC Cancer | 2010
Andreas A. Schnitzbauer; Carl Zuelke; Christian Graeb; Justine Rochon; Itxarone Bilbao; Patrizia Burra; Koert P. de Jong; Christophe Duvoux; Norman M. Kneteman; René Adam; Wolf O. Bechstein; Thomas Becker; Susanne Beckebaum; Olivier Chazouillères; Umberto Cillo; M. Colledan; Fred Fändrich; Jean Gugenheim; Johann Hauss; Michael Heise; Ernest Hidalgo; Neville V. Jamieson; Alfred Königsrainer; P. Lamby; Jan Lerut; Heikki Mäkisalo; Raimund Margreiter; Vincenzo Mazzaferro; Ingrid Mutzbauer; Gerd Otto
BackgroundThe potential anti-cancer effects of mammalian target of rapamycin (mTOR) inhibitors are being intensively studied. To date, however, few randomised clinical trials (RCT) have been performed to demonstrate anti-neoplastic effects in the pure oncology setting, and at present, no oncology endpoint-directed RCT has been reported in the high-malignancy risk population of immunosuppressed transplant recipients. Interestingly, since mTOR inhibitors have both immunosuppressive and anti-cancer effects, they have the potential to simultaneously protect against immunologic graft loss and tumour development. Therefore, we designed a prospective RCT to determine if the mTOR inhibitor sirolimus can improve hepatocellular carcinoma (HCC)-free patient survival in liver transplant (LT) recipients with a pre-transplant diagnosis of HCC.Methods/DesignThe study is an open-labelled, randomised, RCT comparing sirolimus-containing versus mTOR-inhibitor-free immunosuppression in patients undergoing LT for HCC. Patients with a histologically confirmed HCC diagnosis are randomised into 2 groups within 4-6 weeks after LT; one arm is maintained on a centre-specific mTOR-inhibitor-free immunosuppressive protocol and the second arm is maintained on a centre-specific mTOR-inhibitor-free immunosuppressive protocol for the first 4-6 weeks, at which time sirolimus is initiated. A 21/2 -year recruitment phase is planned with a 5-year follow-up, testing HCC-free survival as the primary endpoint. Our hypothesis is that sirolimus use in the second arm of the study will improve HCC-free survival. The study is a non-commercial investigator-initiated trial (IIT) sponsored by the University Hospital Regensburg and is endorsed by the European Liver and Intestine Transplant Association; 13 countries within Europe, Canada and Australia are participating.DiscussionIf our hypothesis is correct that mTOR inhibition can reduce HCC tumour growth while simultaneously providing immunosuppression to protect the liver allograft from rejection, patients should experience less post-transplant problems with HCC recurrence, and therefore could expect a longer and better quality of life. A positive outcome will likely change the standard of posttransplant immunosuppressive care for LT patients with HCC.Trial RegisterTrial registered at http://www.clinicaltrials.gov: NCT00355862(EudraCT Number: 2005-005362-36)
European Journal of Cancer Care | 2009
Andreas Hinz; O. Krauss; Johann Hauss; Michael Höckel; Rolf-Dieter Kortmann; Jens-Uwe Stolzenburg; Reinhold Schwarz
The objective of this study was to compare the prevalence of anxiety and depression in cancer patients with the prevalence found in the general population, using the Hospital Anxiety and Depression Scale (HADS). Participants were 1529 cancer patients treated between 2002 and 2004 in Germany and 2037 persons from the German general population. In the cancer patients, the risk of psychiatric distress was nearly twice that of the general population. While for older age groups (61 years and above) there were only small differences between cancer patients and the general population, the differences in both scales were high for young persons. There were differences between the HADS mean scores of the patients with different tumour localisations, with high values for brain cancer and low scores for prostate cancer. The influence of the tumour stage on anxiety and depression was weak. However, depression scores of patients with a survival time less than 1 year were elevated. The results show that large sample sizes are necessary to evaluate the psychological situation of cancer patients, and that age and gender differences must be taken into account when several samples are compared.
Annals of Surgery | 2007
A. Bembenek; Robert D. Rosenberg; Elke Wagler; S. Gretschel; Andreas Sendler; Joerg-Ruediger Siewert; Jörg Nährig; Helmut Witzigmann; Johann Hauss; Christian Knorr; Arno Dimmler; Jörn Gröne; H. J. Buhr; Jörg Haier; Hermann Herbst; Juergen Tepel; Bence Siphos; Axel Kleespies; Alfred Koenigsrainer; Nikolas H. Stoecklein; Olaf Horstmann; Robert Grützmann; Andreas Imdahl; Daniel Svoboda; Christian Wittekind; Wolfgang Schneider; Klaus-Dieter Wernecke; Peter M. Schlag
Introduction:The clinical impact of sentinel lymph node biopsy (SLNB) in colon cancer is still controversial. The purpose of this prospective multicenter trial was to evaluate its clinical value to predict the nodal status and identify factors that influence these results. Methods:Colon cancer patients without prior colorectal surgery or irradiation were eligible. The sentinel lymph node (SLN) was identified intraoperatively by subserosal blue dye injection around the tumor. The SLN underwent step sections and immunohistochemistry (IHC), if classified free of metastases after routine hematoxylin and eosin examination. Results:At least one SLN (median, n = 2) was identified in 268 of 315 enrolled patients (detection rate, 85%). Center experience, lymphovascular invasion, body mass index (BMI), and learning curve were positively associated with the detection rate. The false-negative rate to identify pN+ patients by SLNB was 46% (38 of 82). BMI showed a significant association to the false-negative rate (P < 0.0001), the number of tumor-involved lymph nodes was inversely associated. If only slim patients (BMI ≤24) were investigated in experienced centers (>22 patients enrolled), the sensitivity increased to 88% (14 of 16). Moreover, 21% (30 of 141) of the patients, classified as pN0 by routine histopathology, revealed micrometastases or isolated tumor cells (MM/ITC) in the SLN. Conclusions:The contribution of SLNB to conventional nodal staging of colon cancer patients is still unspecified. Technical problems have to be resolved before a definite conclusion can be drawn in this regard. However, SLNB identifies about one fourth of stage II patients to reveal MM/ITC in lymph nodes. Further studies must clarify the clinical impact of these findings in terms of prognosis and the indication of adjuvant therapy.
Clinical Cancer Research | 2009
Georg Martin Fiedler; Alexander Benedikt Leichtle; Julia Kase; Sven Baumann; Uta Ceglarek; Klaus Felix; Tim Conrad; Helmut Witzigmann; Arved Weimann; Christof Schütte; Johann Hauss; Markus W. Büchler; Joachim Thiery
Purpose: Mass spectrometry–based serum peptidome profiling is a promising tool to identify novel disease-associated biomarkers, but is limited by preanalytic factors and the intricacies of complex data processing. Therefore, we investigated whether standardized sample protocols and new bioinformatic tools combined with external data validation improve the validity of peptidome profiling for the discovery of pancreatic cancer–associated serum markers. Experimental Design: For the discovery study, two sets of sera from patients with pancreatic cancer (n = 40) and healthy controls (n = 40) were obtained from two different clinical centers. For external data validation, we collected an independent set of samples from patients (n = 20) and healthy controls (n = 20). Magnetic beads with different surface functionalities were used for peptidome fractionation followed by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS). Data evaluation was carried out by comparing two different bioinformatic strategies. Following proteome database search, the matching candidate peptide was verified by MALDI-TOF MS after specific antibody-based immunoaffinity chromatography and independently confirmed by an ELISA assay. Results: Two significant peaks (m/z 3884; 5959) achieved a sensitivity of 86.3% and a specificity of 97.6% for the discrimination of patients and healthy controls in the external validation set. Adding peak m/z 3884 to conventional clinical tumor markers (CA 19-9 and CEA) improved sensitivity and specificity, as shown by receiver operator characteristics curve analysis (AUROCcombined = 1.00). Mass spectrometry–based m/z 3884 peak identification and following immunologic quantitation revealed platelet factor 4 as the corresponding peptide. Conclusions: MALDI-TOF MS-based serum peptidome profiling allowed the discovery and validation of platelet factor 4 as a new discriminating marker in pancreatic cancer.
Atherosclerosis | 2009
Gabriela Aust; Olaf Richter; Silvio Rohm; Christiane Kerner; Johann Hauss; Nora Klöting; Karen Ruschke; Peter Kovacs; Byung-Soo Youn; Matthias Blüher
Obesity is associated with accelerated atherosclerosis. Adipokines may directly influence vessel wall homeostasis by influencing the function of endothelial cells, arterial smooth muscle cells, and modulating inflammation. Recently, visceral adipose tissue-derived serpin (vaspin) was identified as a novel adipokine related to obesity and its metabolic consequences. However, the regulation of vaspin serum concentrations in human atherosclerosis is unknown. We therefore assessed vaspin serum concentrations in 107 consecutive patients with carotid stenosis undergoing carotid endarterectomy (CEA) in relation to severity of atherosclerosis, measures of obesity and circulating markers of obesity and atherosclerosis. Vaspin serum concentrations were significantly lower in patients with carotid stenosis who experienced an ischemic event within 3 months before surgery compared to asymptomatic patients. However, circulating vaspin was not associated with measures of atherosclerosis severity as maximum percentage stenosis. Vaspin serum concentrations were indistinguishable before and after CEA. We found a significant correlation between vaspin and leptin serum concentrations supporting previous results that vaspin closely reflects body fat mass. In conclusion, our data show that low vaspin serum concentrations correlate with recently experienced ischemic events in patients with carotid stenosis despite the lack of an association between circulating vaspin and parameters of atherosclerosis severity.
Transplantation | 2016
Edward K. Geissler; Andreas A. Schnitzbauer; Carl Zülke; P. Lamby; Andrea Proneth; Christophe Duvoux; Patrizia Burra; Karl-Walter Jauch; Markus Rentsch; Tom M. Ganten; Jan Schmidt; Utz Settmacher; Michael Heise; G. Rossi; Umberto Cillo; Norman M. Kneteman; René Adam; Bart van Hoek; Philippe Bachellier; P. Wolf; Lionel Rostaing; Wolf O. Bechstein; Magnus Rizell; James Powell; Ernest Hidalgo; Jean Gugenheim; Heiner Wolters; Jens Brockmann; André G. Roy; Ingrid Mutzbauer
Background We investigated whether sirolimus-based immunosuppression improves outcomes in liver transplantation (LTx) candidates with hepatocellular carcinoma (HCC). Methods In a prospective-randomized open-label international trial, 525 LTx recipients with HCC initially receiving mammalian target of rapamycin inhibitor–free immunosuppression were randomized 4 to 6 weeks after transplantation into a group on mammalian target of rapamycin inhibitor–free immunosuppression (group A: 264 patients) or a group incorporating sirolimus (group B: 261). The primary endpoint was recurrence-free survival (RFS); intention-to-treat (ITT) analysis was conducted after 8 years. Overall survival (OS) was a secondary endpoint. Results Recurrence-free survival was 64.5% in group A and 70.2% in group B at study end, this difference was not significant (P = 0.28; hazard ratio [HR], 0.84; 95% confidence interval [95% CI], 0.62; 1.15). In a planned analysis of RFS rates at yearly intervals, group B showed better outcomes 3 years after transplantation (HR, 0.7; 95% CI, 0.48-1.00). Similarly, OS (P = 0.21; HR, 0.81; 95% CI, 0.58-1.13) was not statistically better in group B at study end, but yearly analyses showed improvement out to 5 years (HR, 0.7; 95% CI, 0.49-1.00). Interestingly, subgroup (Milan Criteria-based) analyses revealed that low-risk, rather than high-risk, patients benefited most from sirolimus; furthermore, younger recipients (age ⩽60) also benefited, as well sirolimus monotherapy patients. Serious adverse event numbers were alike in groups A (860) and B (874). Conclusions Sirolimus in LTx recipients with HCC does not improve long-term RFS beyond 5 years. However, a RFS and OS benefit is evident in the first 3 to 5 years, especially in low-risk patients. This trial provides the first high-level evidence base for selecting immunosuppression in LTx recipients with HCC.