S Hollerbach

Hannover Medical School, Hanover, Lower Saxony, Germany

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Publications (83)422.72 Total impact

  • Zeitschrift für Gastroenterologie 08/2015; 41(08). DOI:10.1055/s-0035-1555552 · 1.67 Impact Factor
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    ABSTRACT: BACKGROUND: We evaluated the feasibility and tolerability of triple- versus double-drug chemotherapy in elderly patients with oesophagogastric cancer. METHODS: Patients aged 65years or older with locally advanced or metastatic oesophagogastric cancer were stratified and randomised to infusional 5-FU, leucovorin and oxaliplatin without (FLO) or with docetaxel 50mg/m(2) (FLOT) every 2weeks. The study is registered at ClinicalTrials.gov, identifier NCT00737373. FINDINGS: One hundred and forty three (FLO, 71; FLOT, 72) patients with a median age of 70years were enrolled. The triple combination was associated with more treatment-related National Cancer Institute Common Toxicity Criteria (NCI-CTC) grade 3/4 adverse events (FLOT, 81.9%; FLO, 38.6%; P<.001) and more patients experiencing a ⩾10-points deterioration of European Organization for Research and Treatment of Cancer Quality of Life (EORTC QoL) global health status scores (FLOT, 47.5%; FLO 20.5%; p=.011). The triple combination was associated with more alopecia (P<.001), neutropenia (P<.001), leukopenia (P<.001), diarrhoea (P=.006) and nausea (P=.029).). No differences were observed in treatment duration and discontinuation due to toxicity, cumulative doses or toxic deaths between arms. The triple combination improved response rates and progression-free survival in the locally advanced subgroup and in the subgroup of patients aged between 65 and 70years but not in the metastatic group or in patients aged 70years and older. INTERPRETATION: The triple-drug chemotherapy was feasible in elderly patients with oesophagogastric cancer. However, toxicity was significantly increased and QoL deteriorated in a relevant proportion of patients. FUNDING: The study was partially funded by Sanofi-Aventis.
    European journal of cancer (Oxford, England: 1990) 10/2012; 49(4). DOI:10.1016/j.ejca.2012.09.025 · 4.82 Impact Factor
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    ABSTRACT: Background More than half of patients with colorectal cancer will develop metastatic disease either evident at the time of initial diagnosis or during their course of disease. Besides multidisciplinary management further treatment intensification is warranted to improve the still limited prognosis. Methods/design In these two multi-centre, randomized phase II trials, conducted in Germany, 380 patients with R0-resectable colorectal liver metastases (PERIMAX) and with unresectable, metastatic colorectal cancer (CHARTA) will be recruited. Patients previously untreated for metastatic disease with either synchronous or metachronous metastases are randomly assigned in a 1:1 ratio to resection of colorectal liver metastases followed by postoperative FOLFOX for 6 months or perioperative FOLFOXIRI and bevacizumab for 3 months pre- and postoperative and resection (PERIMAX), or to induction chemotherapy with FOLFOX and bevacizumab +/− irinotecan for a maximum of 6 months followed by maintenance treatment with fluoropyrimidine and bevacizumab. The primary objective of these trials is to evaluate the feasibility and efficacy of FOLFOXIRI and bevacizumab in metastatic colorectal cancer. Primary endpoint is failure free survival rate at 18 months in the PERIMAX trial and progression free survival rate at 9 months in CHARTA. Secondary objectives include efficacy, safety and tolerability. Discussion The CHARTA and PERIMAX trials are designed to evaluate the benefits and limitations of a highly active four-drug regimen in distinct treatment situations of metastatic CRC. Eligible patients are classified into resectable liver metastases to be randomized to perioperative treatment with FOLFOXIRI and bevacizumab or postoperative FOLFOX in the PERIMAX, or unresectable metastatic CRC to be randomized between FOLFOX and bevacizumab with or without irinotecan, stratified for clinical groups according to disease and patients’ characteristics in the CHARTA trial. Trial registration Clinical trial identifier CHARTA: NCT01321957, PERIMAX: NCT01540435
    BMC Cancer 08/2012; 12(1):356. DOI:10.1186/1471-2407-12-356 · 3.32 Impact Factor
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    ABSTRACT: BI 2536, a novel Polo-like kinase 1 inhibitor, was assessed in patients with unresectable advanced exocrine adenocarcinoma of the pancreas. The study employed a two-stage design. Randomised first-line patients received BI 2536 200 mg on day 1 (n=43) or 60 mg on days 1-3 (n=43) every 21 days. Recruitment of second-line patients was planned for a second stage dependent on an interim analysis demonstrating ≥ 2 responses in the first 18 evaluable patients following 12 weeks of treatment and/or tumour control ≥ 12 weeks in 5 patients per schedule. Primary end point was objective response rate (ORR). By independent review, ORR was 2.3% (all partial) and 24.4% had stable disease as confirmed best response. The second stage was not initiated. Median overall and progression-free survivals were 149 (95% confidence interval (CI), 91-307) and 46 days (95% CI, 44-56). Most common drug-related adverse events were neutropenia (37.2%), leukopenia (29.1%), fatigue (29.1%) and nausea (22.1%); most common grade 3/4-related events were neutropenia (36.0%), leukopenia (27.9%) and thrombocytopenia (8.1%). Given the low ORR and poor survival, further development of BI 2536 monotherapy is not warranted in this population.
    British Journal of Cancer 06/2012; 107(2):280-6. DOI:10.1038/bjc.2012.257 · 4.82 Impact Factor
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    ABSTRACT: Objective and setting: The aim of this prospective study was to compare the clinical predictive values of the Glasgow Coma Scale (GCS) and somatosensory-evoked potentials (SEP) in the assessment of neurological outcome in pati-ents with anoxic brain damage following cardiopulmonary resuscitation. Subjects and interventions: We repeatedly obtained GCS values and recorded cervicomedullary and cortical SEPs during the clinical course of 20 consecutive patients (median age: 61 years). SEPs were performed according to standard techniques and recordings were done using the interna-tional 10/20 system of electrode placement. In the majority of patients early brainstem auditory-evoked potentials (BAEP; n=14) and cranial computed tomography (CCT; n=12) were initially recorded. Endpoint: The neurological outcome score determined both at the time after completing intensive care treatment and at clinical follow-up (1-5 months) served as a reference. The patients were subdivided into three groups according to neurological outcome (I=excellent, II=moderate to severe disabilities and III=bad, including death and persistent vegetative state). Measurements and main results: Ten of 12 patients in Group III died and two remained in a persistent vegetative state; neither of these regained consciousness. Only two patients in both Groups I and II died, the others had no (n=4; Group I) or moderate (n=2; Group II) neurological deficits. The GCS values which were initially determined (GCS I) could not sufficiently predict outcome. In contrast, the GCS obtained at the time of discharge from ICU (GCS III) showed a distinct difference between Groups I and III. The positive predictive value (PPV) of GCS I for outcome in Groups I and II was 67% but the PPV of GCS III in this setting was 89%. Eight of 12 patients in Group III had bilaterally, and two unilaterally absent cortical N20 waves in their initial SEP recordings, whereas in all eight patients of both Groups I and II the cortical N20 wave was preserved. The PPV of the absent N20 wave for outcome Group III was 100%. In only one patient CCT demonstrated a specific sign of acute brain injury (brain oedema). The initial BAEP recordings did not significantly differ in terms of altered latencies or amplitudes among the different outcome groups and no missing peaks were observed. Conclusions: In patients with hypoxic brain damage following cardiopulmonary resuscitation the bilateral absence of the N20 wave in cortical SEP recordings predicts a fatal clinical outcome in virtually all cases at an early stage. The initial outcome prediction by the GCS is hampered by individual variations and the influence of medications but repeated testing during the clinical course correlates well with the final outcome.
    Clinical Intensive Care 12/2011; 6(5). DOI:10.1080/714028907
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    ABSTRACT: Genetic alterations within the epidermal growth factor receptor (EGFR) pathway, including KRAS mutations, have been demonstrated to be associated with response to EGFR inhibitors like cetuximab in colorectal cancers. Mutations in the KRAS gene have been found in 70-90% of pancreatic cancers. Unfortunately, the addition of cetuximab to chemotherapy did not increase response or survival in patients with advanced pancreatic cancer in phase II and phase III studies. The aim of this study was to evaluate the relationship between KRAS mutations and response or survival in patients with metastatic pancreatic cancer treated with cetuximab plus chemotherapy. Within a multicenter phase II trial, 64 patients with metastatic pancreatic cancer were treated with cetuximab in combination with gemcitabine and oxaliplatin until disease progression. Analyses of the EGFR pathway, including KRAS mutations, could be performed in 25 patients. Analyses were carried out following microdissection of the tumor. Fourteen (56%) of the 25 patients examined harbored a point mutation in codon 12 of the KRAS gene. No differences between the groups were noted in median progression-free survival (104 days in KRAS wild-type patients vs. 118 days in patients with KRAS mutations). Overall survival was longer in wild-type patients compared to patients with KRAS mutations (263 vs. 162 days), but the difference did not reach statistical significance. A further analysis of our clinical phase II trial showed that the presence of a rash was significantly correlated with overall survival. KRAS mutation in codon 12 may be associated with reduced survival compared to KRAS wild type. The role of KRAS mutations for cetuximab therapy in pancreatic cancer warrants further investigation in larger trials to exclude an epiphenomenon. Furthermore, the development of a rash is indicative of clinical benefit.
    Oncology 09/2011; 81(1):3-8. DOI:10.1159/000330194 · 2.61 Impact Factor
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    ABSTRACT: Capsule endoscopy (CE) and double-balloon enteroscopy (DBE) detect small bowel bleeding with equal diagnostic yield. We aimed to detect factors that influence procedural cost of CE and DBE in diagnosing and treating small bowel bleeding, and to compare them with reimbursement. A cost model analysed procedural cost for diagnostic CE versus diagnostic, unidirectional DBE(scenario 1) and CE plus directed therapeutic DBE(positive findings in CE) versus unidirectional diagnostic plus therapeutic DBE (scenario 2). The frequency of investigations per annum (p.a.) at which cost per procedure is equalized (break-even point) was determined for CE versus DBE. A retrospectively collected cohort of patients was used to validate the cost model and to compare procedural costs with reimbursement (German diagnosis related groups, G-DRG). The break-even point at which cost per procedure is equalized for CE versus DBE was reached at 100 procedures p.a. in scenario 1 and 79 in scenario 2 for a rate of therapeutic enteroscopy of 14%, and 27 for a therapeutic enteroscopy rate of 30%. Personnel cost, procedure time,procedures p.a. and the rate of therapeutic enteroscopy had a major influence on procedural cost. In this patient cohort, the 'CE-first' and the 'DBE-first' strategies produced procedural costs of pound sterling 830 and pound sterling 1,076 per patient to attain a diagnosis, and pound sterling 1,042 versus pound sterling 1,181 to achieve therapeutic enteroscopy, respectively. For this cohort, potential reimbursement was pound sterling 2,320 and pound sterling 3,047 for the 'CE-first' and the 'DBE-first' strategies, respectively (G-DRG). Workflow management of CE versus DBE should consider frequency of investigations p.a. and probability for therapeutic enteroscopy to minimize procedural costs. The cost of DBE increases with less frequent or time-consuming investigations; CE is more robust with regard to these factors. From a third-party payer perspective, a strategy incorporating CE seems to minimize costs in G-DRG.
    European journal of gastroenterology & hepatology 06/2010; 22(6):679-88. DOI:10.1097/MEG.0b013e32832ca07d · 2.15 Impact Factor
  • Zeitschrift für Gastroenterologie 09/2009; 47(09). DOI:10.1055/s-0029-1241476 · 1.67 Impact Factor
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    ABSTRACT: Targeting the epidermal growth factor receptor pathway in pancreatic cancer seems to be an attractive therapeutic approach. This study assessed the efficacy of cetuximab plus the combination of gemcitabine/oxaliplatin in metastatic pancreatic cancer. Eligible subjects had histological or cytological diagnosis of metastatic pancreatic adenocarcinoma. The primary end point was response according to RECIST. Patients received cetuximab 400 mg m(-2) at first infusion followed by weekly 250 mg m(-2) combined with gemcitabine 1000 mg m(-2) as a 100 min infusion on day 1 and oxaliplatin 100 mg m(-2) as a 2-h infusion on day 2 every 2 weeks. Between January 2005 and August 2006, a total of 64 patients (22 women (34%), 42 men (66%); median age 64 years (range 31-78)) were enrolled at seven study centres. On October 2007, a total of 17 patients were alive. Sixty-two patients were evaluable for baseline and 61 for assessment of response to treatment in an intention-to-treat analysis. Six patients had an incomplete drug combination within the first cycle of the treatment plan (n=4 hypersensitivity reactions to the first cetuximab infusion, n=2 refused to continue therapy). Reported grade 3/4 toxicities (% of patients) were leukopaenia 15%, anaemia 8%, thrombocytopaenia 10%, diarrhoea 7%, nausea 18%, infection 18% and allergy 7%. Cetuximab-attributable skin reactions occurred as follows: grade 0: 20%, grade 1: 41%, grade 2: 30% and grade 3: 10%. The intention-to-treat analysis of 61 evaluable patients showed an overall response rate of 33%, including 1 (2%) complete and 19 (31%) partial remissions. There were 31% patients with stable and 36% with progressive disease or discontinuation of the therapy before re-staging. The presence of a grade 2 or higher skin rash was associated with a higher likelihood of achieving objective response. Median time to progression was 118 days, with a median overall survival of 213 days. A clinical benefit response was noted in 24 of the evaluable 61 patients (39%). The addition of cetuximab to the combination of gemcitabine and oxaliplatin is well tolerated but does not increase response or survival in patients with metastatic pancreatic cancer.
    British Journal of Cancer 05/2009; 100(7):1032-6. DOI:10.1038/sj.bjc.6604983 · 4.82 Impact Factor
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    ABSTRACT: This study was designed to compare fluorouracil, leucovorin, and oxaliplatin with fluorouracil, leucovorin, and cisplatin in patients with advanced gastric cancer. Patients with previously untreated advanced adenocarcinoma of the stomach or esophagogastric junction were randomly assigned to receive either fluorouracil 2,600 mg/m(2) via 24-hour infusion, leucovorin 200 mg/m(2), and oxaliplatin 85 mg/m(2) (FLO) every 2 weeks or fluorouracil 2,000 mg/m(2) via 24-hour infusion, leucovorin 200 mg/m(2) weekly, and cisplatin 50 mg/m(2) every 2 weeks (FLP). The primary end point was progression-free survival (PFS). Two hundred twenty patients (median age, 64 years; metastatic, 94%) were randomly assigned. FLO was associated with significantly less (any grade) anemia (54% v 72%), nausea (53% v 70%), vomiting (31% v 52%), alopecia (22% v 39%), fatigue (19% v 34%), renal toxicity (11% v 34%), thromboembolic events (0.9% v 7.8%), and serious adverse events related to the treatment (9% v 19%). FLP was associated with significantly less peripheral neuropathy (22% v 63%). There was a trend toward improved median PFS with FLO versus FLP (5.8 v 3.9 months, respectively; P = .077) and no significant difference in median overall survival (10.7 v 8.8 months, respectively). However, in patients older than 65 years (n = 94), treatment with FLO resulted in significantly superior response rates (41.3% v 16.7%; P = .012), time to treatment failure (5.4 v 2.3 months; P < .001), and PFS (6.0 v 3.1 month; P = .029) and an improved OS (13.9 v 7.2 months) as compared with FLP, respectively. FLO reduced toxicity as compared with FLP. In older adult patients, FLO also seemed to be associated with improved efficacy.
    Journal of Clinical Oncology 03/2008; 26(9):1435-42. DOI:10.1200/JCO.2007.13.9378 · 18.43 Impact Factor
  • EJC Supplements 09/2007; 5(4):269-269. DOI:10.1016/S1359-6349(07)71036-4 · 9.39 Impact Factor
  • EJC Supplements 09/2007; 5(4):259-260. DOI:10.1016/S1359-6349(07)71005-4 · 9.39 Impact Factor
  • A. Trummer · F. Wiedbrauck · S. Hollerbach
    12/2006: pages 179-183;
  • Arne Trummer · Karl-Jürgen Oldhafer · Peer Flemming · Stephan Hollerbach
    Gastrointestinal Endoscopy 11/2006; 64(4):658-60. DOI:10.1016/j.gie.2006.04.013 · 4.90 Impact Factor
  • S Hollerbach · E Burmester
    Zeitschrift für Gastroenterologie 05/2006; 44(4):350-3. · 1.67 Impact Factor
  • KA Papadakis · S K Lo · Z Fireman · S Hollerbach
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    ABSTRACT: Wireless capsule endoscopy (WCE) is a novel, noninvasive technique that can detect obscure mucosal lesions along the entire length of the small bowel. Early systematic studies of WCE in patients with Crohn's disease suggest that this technique is a very effective diagnostic too] in patients with a high clinical probability of having the disease, but whose classic endoscopic and radiographic studies have been negative. It is likely that WCE will replace radiographic studies in this setting in the near future. A careful clinical history must be taken and imaging studies of the small bowel are mandatory prior to WCE in patients with inflammatory bowel disease, in order to avoid the rare complication of capsule retention in intestinal strictures, although the use of the "patency capsule" will probably greatly facilitate the exclusion of relevant strictures in the near future.
    Endoscopy 11/2005; 37(10):1018-22. DOI:10.1055/s-2005-870263 · 5.20 Impact Factor
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    S Elsenbruch · L Wang · S Hollerbach · M Schedlowski · G Tougas
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    ABSTRACT: We analysed visceromotor (VMR) and corticosterone responses to colorectal stimuli under control conditions and following acoustic stress in rats selectively bred for increased sensitivity to cholinergic agonists, the Flinders Sensitive Line (FSL) rats, compared with Flinders Resistant Line (FRL) rats. FSL rats demonstrated a significant VMR response at the smallest distension pressure, whereas no response was evident in FRL controls. FSL rats also demonstrated enhanced VMR responses at both larger distension levels compared with FRL rats. Colorectal distension (CRD) produced significant increases in serum corticosterone levels, which were comparable in FRL and FSL. Noise stress induced divergent corticosterone responses in FRL and FSL, but did not affect VMR to CRD in either group. These data suggest that FSL rats show altered VMR responses to CRD and disturbed hypothalamic-pituitary-adrenal axis responses to acute stress.
    Neurogastroenterology and Motility 01/2005; 16(6):801-9. DOI:10.1111/j.1365-2982.2004.00563.x · 3.42 Impact Factor
  • F Wiedbrauck · S Hollerbach
    Zeitschrift für Gastroenterologie 01/2005; 43(05). DOI:10.1055/s-2005-919877 · 1.67 Impact Factor
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    ABSTRACT: Endoscopic ultrasound (EUS)-guided fine-needle aspiration biopsy (EUS-FNA) is increasingly used for the diagnosis of malignant and benign disease in the region of the upper GI tract. We prospectively investigated the clinical accuracy and safety of this method in unselected patients under routine conditions. 101 consecutive patients (median 61.5 years; 56 female) were enrolled in the study, in whom a total of 106 tissue biopsies were obtained by using EUS-FNA. Major indications for EUS-FNA were suspicious lesions located in the mediastinum, esophagus, stomach, pancreas, liver, biliary system, adrenals or retroperitoneum. A longitudinal echoendoscope (HITACHI FG-34UX) equipped with a standard 22G -aspiration needle was used. The aspirated specimens were analyzed further by using standard cytology and/or histology. Lymph-node biopsies were additionally subjected to flow-cytometry (FACS-light-chain restriction). Surgery was used for reference (where available). In the remaining cases the final diagnosis obtained by the clinical course and all available imaging and histologic informations (ultrasound, CT, MRT) was used for reference. EUS-FNA caused no serious complications. In 6/106 specimen (5.6 %) no sufficient cell material could be aspirated. In the remaining 100 specimens EUS-FNA reached an overall sensitivity of 78 % and a specificity of 100 %, while the accuracy was 89 % and the positive and negative predictive values were 100 % and 81 %, respectively. The greatest diagnostic accuracy was achieved in mediastinal and retroperitoneal lesions, while the accuracy of EUS-FNA in pancreatic lesions and perigastric lymph nodes was distinctly smaller (<80 %). Addition of FACS studies in patients with suspected malignant lymphoma increased the diagnostic accuracy in the small number of patients included in the study. EUS-FNA improves the tissue-based diagnosis of suspicious lesions in locations that are difficult to access (e. g., posterior mediastinum). EUS-FNA is safe, while its diagnostic accuracy is relatively high. Our preliminary data suggest that flow-cytometry may improve the fine-needle based diagnosis of non-Hodgkin s lymphoma, which should be further investigated.
    DMW - Deutsche Medizinische Wochenschrift 11/2004; 129(42):2227-32. · 0.55 Impact Factor
  • DMW - Deutsche Medizinische Wochenschrift 10/2004; 129(42):2227-2232. DOI:10.1055/s-2004-831867 · 0.55 Impact Factor

Publication Stats

1k Citations
422.72 Total Impact Points

Institutions

  • 2006–2012
    • Hannover Medical School
      Hanover, Lower Saxony, Germany
  • 2004–2012
    • Allgemeines Krankenhaus Celle
      Celle, Lower Saxony, Germany
  • 2005
    • Hillel Yaffe Medical Center
      Hědērā, Haifa, Israel
  • 2001–2005
    • Ruhr-Universität Bochum
      • Faculty of Medicine
      Bochum, North Rhine-Westphalia, Germany
  • 2003
    • Sana Kliniken Lübeck GmbH
      Lübeck Hansestadt, Schleswig-Holstein, Germany
  • 1999–2001
    • Universität Regensburg
      • Department of Internal Medicine I
      Ratisbon, Bavaria, Germany
  • 1997–2000
    • McMaster University
      • • Division of Gastroenterology
      • • Department of Medicine
      Hamilton, Ontario, Canada