S Hollerbach

Hannover Medical School, Hanover, Lower Saxony, Germany

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Publications (80)378.47 Total impact

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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. · 5.08 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).
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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. · 2.17 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. · 5.08 Impact Factor
  • Ejc Supplements - EJC SUPPL. 01/2007; 5(4):269-269.
  • S Hollerbach, E Burmester
    Zeitschrift für Gastroenterologie 05/2006; 44(4):350-3. · 1.41 Impact Factor
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    ABSTRACT: Esophageal electrical stimulation using short and a relatively small number of (200 micros, 0.2 Hz, n = 25) electrical pulses generates a characteristic and well defined cortical evoked potential response (EP). There are two methods of stimulation: either through intraesophageal electrodes or with transmural electrodes. The objective of this paper is to compare EP response, sensations and heart rate variability power spectra elicited by both stimulation modalities in healthy volunteers. Our results suggest that transmural stimulation is more accurately perceived and at lower intensities, produces more reproducible peaks of higher amplitude than during intraesophageal stimulation. During either mode of esophageal stimulation, power within the high-frequency component of the heart rate variability power spectrum is enhanced.
    IEEE Transactions on Biomedical Engineering 05/2005; 52(4):736-9. · 2.35 Impact Factor
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    ABSTRACT: At present, surveillance of premalignant small bowel polyps in hereditary polyposis syndromes has a number of limitations. Capsule endoscopy (CE) is a promising new method to endoscopically assess the entire length of the small bowel. We prospectively examined 40 patients with hereditary polyposis syndromes (29 familial adenomatous polyposis (FAP), 11 Peutz-Jeghers syndrome (PJS)). Results were compared with push-enteroscopy (PE) results in FAP and with esophagogastroduodenoscopy, PE, (MR)-enteroclysis, and surgical specimen in PJS patients. A total of 76% of the patients with FAP with duodenal adenomas (n = 21) had additional adenomas in the proximal jejunum that could be detected by CE and PE. Moreover, 24% of these FAP patients had further polyps in the distal jejunum or ileum that could only be detected by CE. In contrast, in FAP patients without duodenal polyps (n = 8), jejunal or ileal polyps occurred rarely (12%). CE detected polyps in 10 of 11 patients with PJS, a rate superior to all other reference procedures employed. Importantly, the findings of CE had immediate impact on further clinical management in all PJS patients. Our results suggest that CE may be of clinical value in selected patients with FAP, whereas in PJS, CE could be used as first line surveillance procedure.
    The American Journal of Gastroenterology 02/2005; 100(1):27-37. · 9.21 Impact Factor
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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. · 2.94 Impact Factor
  • 12/2004: pages 732-761;
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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. · 0.65 Impact Factor
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    ABSTRACT: The video-capsule endoscopy (CE) of the small intestine is a novel innovative procedure for outpatient use that can detect even small lesions of the mucosa of the small intestine. Aim of this retrospective clinical study was to evaluate the diagnostic value of CE in a clinical routine setting. Between July 2001 and October 2002 we investigated 42 patients with suspected gastrointestinal bleeding by CE. In all patients, the previous upper and lower endoscopy work-up was normal. In some cases additional procedures such as bloodpool scintigraphy, angiography, small-bowel enteroclysis or push-enteroscopy were performed. CE detected relevant pathological findings in 23 out of 42 Patients (55 %). The majority of findings in the CE consisted of angiodysplasia (n = 16), ulcer and haemorrhagical erosions (n = 10), one Ulcus Dieulafoy and additional polyps of the small intestine (n = 2). In 4 cases an inflammatory small-bowel disease was detected. These findings could be confirmed by Re-endoscopy. The information provided was helpful to direct further diagnostic and treatment options. In 14 cases (33 %) CE-findings steered additional diagnostic and therapeutic steps. We conclude that CE is safe and has a high diagnostic yield. M2A video CE is likely to become an integral part of the algorithm of diagnostic of occult gastrointestinal bleeding after exclusion of other causes of anemia and negative upper and lower endoscopy work-up.
    DMW - Deutsche Medizinische Wochenschrift 07/2004; 129(24):1369-74. · 0.65 Impact Factor
  • S Hollerbach, E Burmester
    Zeitschrift für Gastroenterologie 03/2004; 42(2):193-7. · 1.41 Impact Factor
  • S. Hollerbach, K. Schulmann
    Endoscopy 01/2004; 36(6):563-564. · 5.74 Impact Factor
  • Deutsche Medizinische Wochenschrift - DEUT MED WOCHENSCHR. 01/2004; 129(24):1369-1374.
  • Deutsche Medizinische Wochenschrift - DEUT MED WOCHENSCHR. 01/2004; 129(42):2227-2232.
  • Gastrointestinal Endoscopy - GASTROINTEST ENDOSCOP. 01/2004; 59(5).
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    K Schulmann, S Hollerbach, W Schmiegel
    Gut 11/2003; 52(10):1531-2; author reply 1532. · 10.73 Impact Factor
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    ABSTRACT: Hepatocellular carcinoma (HCC) is the most common primary malignancy arising within the liver and most often affects individuals with chronic hepatitis and/or liver cirrhosis. Patients often present at an advanced stage of disease or with poor liver function, thus limiting treatment options and resulting in a poor prognosis of the disease. Therefore, an early tissue-based diagnosis of HCC is necessary to direct further work-up and treatment. We present the case of a 70-year-old man with alcoholic cirrhosis at stage Child C, in whom a tumor nodule was found incidentally within the left lobe of the liver. Percutaneous biopsy was deemed too dangerous because a deteriorated liver function with coagulopathy was present, and a significant amount of ascites surrounded the small cirrhotic liver. To obtain a conclusive diagnosis, we performed transgastric fine-needle biopsy of the tumor under direct endosonographic guidance (EUS-FNA) without complications. Cytologic examination confirmed the presence of a well differentiated HCC. Based on this finding, super-selective CT-guided angiography and chemoembolization were subsequently performed without complications and the patient remained free of tumor relapse for the 8 months of surveillance. We conclude that EUS-guided fine-needle biopsy and cytologic examination represent a reliable alternative for tissue sampling in HCC, particularly in selected high-risk patients such as those with poor liver function and coagulation disorders; this should be assessed in prospective clinical trials.
    Zeitschrift für Gastroenterologie 11/2003; 41(10):995-8. · 1.41 Impact Factor
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    ABSTRACT: EUS-guided fine-needle aspiration biopsy (EUS-FNA) is used increasingly for the diagnosis of mediastinal, biliopancreatic, and gastric tumors. However, little is known about EUS-FNA in hepatic lesions and the best method for tissue analysis. We assessed EUS-FNA combined with histological and cytological evaluation in selected patients. 41 patients (66 +/- 7 years) were prospectively studied, 33 of whom had clinical findings suggestive of liver malignancies. Selection for EUS-FNA was based on an increased risk of bleeding from percutaneous biopsy (coagulopathy, cirrhosis, ascites, aspirin intake; n = 15), presence of small liver tumors < 2 cm (n = 12), or liver lesions found incidentally (n = 14). Transgastric EUS-FNA of lesions located in accessible liver segments was performed using the Hitachi FG-34UX longitudinal echo endoscope and a 22-G aspiration needle. Specimens were submitted separately for standard cytological and histological evaluation. In the case of malignancies, findings at surgery with histological examination, endoscopy, or computed tomography (CT)-guided biopsy of the primary cancer served as reference results (n = 33), while in benign disorders, a combination of imaging studies (Magnetic Resonance Tomography , scintigraphy) and the clinical follow-up, as summarized in the physician's report, was used as reference. EUS-FNA provided appropriate biopsy specimens in 40/41 patients. It was not possible to aspirate sufficient material in one patient. On average, 1.4 needle passes were necessary to obtain sufficient amounts of tissue. With regard to malignancy, the combination of histological and cytological examination had a sensitivity of 94%, specificity of 100%, negative predictive value (NPV) of 78%, and positive predictive value (PPV) of 100%. Tissue diagnoses were in agreement in 27/41 patients (65%). In the remaining patients, only the cytological examination identified six lesions correctly, while the histological assessment was correct in another seven patients. Malignant lesions were correctly identified by cytology in 24/33 (73%) patients, while histology alone was diagnostic for malignancy in 27/33 (82%) patients. When both modalities were combined, 31 out of 33-malignancies (94%) were correctly diagnosed. Minor complications occurred in two patients and consisted of self-limiting local bleeding. EUS-FNA of liver tumors is a powerful, reliable, and safe procedure for the diagnosis of malignant liver lesions. Optimal diagnostic results are achieved by combining cytological with histological assessment. Hence, EUS-FNA is an alternative to percutaneous biopsy, particularly in patients at risk of bleeding or with small lesions of the liver.
    Endoscopy 09/2003; 35(9):743-9. · 5.74 Impact Factor

Publication Stats

853 Citations
378.47 Total Impact Points

Institutions

  • 2012
    • Hannover Medical School
      Hanover, Lower Saxony, Germany
  • 1993–2011
    • Universität Regensburg
      • Lehrstuhl für Innere Medizin I
      Regensburg, Bavaria, Germany
  • 2004–2006
    • Allgemeines Krankenhaus Celle
      Celle, Lower Saxony, Germany
  • 2005
    • University Hospital Essen
      • Institut für Medizinische Psychologie und Verhaltensimmunbiologie
      Essen, North Rhine-Westphalia, Germany
  • 2001–2005
    • Ruhr-Universität Bochum
      • Medizinische Fakultät
      Bochum, North Rhine-Westphalia, Germany
  • 2003
    • Sana Kliniken Lübeck GmbH
      Lübeck Hansestadt, Schleswig-Holstein, Germany
  • 1997–2000
    • McMaster University
      • • Division of Pediatric Gastroenterology
      • • Department of Medicine
      Hamilton, Ontario, Canada