Frank Bergmann

Universität Heidelberg, Heidelburg, Baden-Württemberg, Germany

Are you Frank Bergmann?

Claim your profile

Publications (107)470.46 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Because neural invasion (NI) is still inconsistently reported and not well characterized within gastrointestinal malignancies (GIMs), our aim was to determine the exact prevalence and severity of NI and to elucidate the true impact of NI on patient's prognosis.
    Annals of surgery. 11/2014; 260(5):900-908.
  • [Show abstract] [Hide abstract]
    ABSTRACT: This study aimed to analyze a large single-center population of resected intraductal papillary mucinous neoplasms (IPMN) of the pancreas with respect to risk factors of malignant transformation.
    Annals of surgery. 11/2014; 260(5):848-856.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Radical resection with total mesorectal excision (TME) is the accepted standard of care for most rectal cancers. However, T1 rectal cancers may be at low risk for metastases and are therefore treatable with local resection. The aim of our study was to investigate whether the identification of these patients is possible through existing selection criteria.
    Annals of Surgical Oncology 10/2014; · 3.94 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Pancreatic acinar cell carcinomas (PACs) are rare but are distinct aggressive neoplasms that phenotypically differ from pancreatic ductal adenocarcinomas (PDACs) and pancreatic neuroendocrine neoplasms (PNENs). Despite recent work on the genetic changes of PACs, their molecular pathogenesis is still poorly understood. In this study, we focus on a comparative genomic hybridization analysis. Based on frequent chromosomal imbalances, the involvement of DCC and c-MYC in the pathogenesis of PACs is further investigated. Moreover, we examine markers harboring potential therapeutic relevance (K-RAS, BRAF, EGFR, MGMT, HSP90, L1CAM, Her2). PACs revealed a microsatellite stable, chromosomal unstable genotype, defined by recurrent chromosomal losses of 1p, 3p, 4q, 5q, 6q, 8p, 9p, 11q, 13q, 16q, and 18, as well as gains of 1q, 7, 8q, 12, 17q, and 20q. Subsets of PAC displayed reduction/loss of DCC (79 %) and c-MYC-amplification (17 %). Significant EGFR expression occurred in 42 %, HSP90 expression in 98 %, L1CAM expression in 72 %, and loss of MGMT in 26 %. Two cases carried a K-RAS mutation. Mutations of EGFR or BRAF were not detected. All cases were Her2/neu-negative. PACs display characteristic chromosomal imbalances which are distinctly different from those in pancreatic ductal adenocarcinomas and pancreatic neuroendocrine neoplasms. Our findings suggest that DCC and c-MYC alterations may play an important role in the pathogenesis of PACs. Furthermore, EGFR, MGMT, HSP90, and L1CAM may be useful as therapeutic markers and predictors of response to therapy in a subset of PACs.
    Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 10/2014; · 2.56 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Solid pseudopapillary neoplasms of the pancreas (SPN) are rare tumors. There is no standard treatment for patients with unresectable liver metastases of SPN. We describe a 40-year-old woman with SPN and metastases confirmed to the liver, and disease progression after primary tumor resection and chemotherapy with gemcitabine and cisplatin. The patient was treated with chemosaturation with percutaneous hepatic perfusions of melphalan. The procedure was performed twice within 8 weeks after which the liver metastases showed a marked reduction in size and vascularization (partial response). Grade 3 leukopenia after the second procedure was managed effectively with granulocyte colony-stimulating factor. No other toxicities were observed. Ten months after initiating treatment, the patient had a good performance status and remained stable. For SPN with unresectable liver metastases and progression despite systemic treatment, repeat chemosaturation with high-dose melphalan may offer an effective regional treatment option.
    Pancreatology 09/2014; · 2.50 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background The incidence of pancreatic neuroendocrine neoplasms (pNEN) is increasing. This study aimed to evaluate predictors of overall survival and the indication for surgery.Methods Data collected between October 2001 and December 2012 were analysed. Histological grading and staging was based on the classifications of the World Health Organization, the International Union Against Cancer and the European Neuroendocrine Tumour Society.ResultsSome 310 patients (150 female, 48·4 per cent) underwent surgical resection. The final survival analysis included 291 patients. Five-year overall survival differed according to tumour grade (G): 91·0 per cent among 156 patients with pancreatic neuroendocrine tumours (pNET) G1, 70·8 per cent in 111 patients with pNET G2, and 20 per cent in 24 patients with pancreatic neuroendocrine carcinomas (pNEC) G3 (P < 0·001). Tumours graded G3 (hazard ratio (HR) 6·96, 95 per cent confidence interval 3·67 to 13·21), the presence of distant metastasis (HR 2·41, 1·32 to 4·42) and lymph node metastasis (HR 2·10, 1·07 to 4·16) were independent predictors of worse survival (P < 0·001, P = 0·004 and P = 0·032 respectively). Eight of 61 asymptomatic patients with pNEN smaller than 2 cm had tumours graded G2 or G3, and six of 51 patients had lymph node metastasis. Among patients with pNEC G3, the presence of distant metastasis had a significant impact on the 5-year overall survival rate: 0 per cent versus 43 per cent in those without distant metastasis (P = 0·036).Conclusion Neuroendocrine tumours graded G3, lymph node and distant metastasis are independent predictors of worse overall survival in patients with pNEN.
    British Journal of Surgery 08/2014; · 4.84 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The biology of pancreatic acinar cell cystadenomas has not been clearly defined. However, a non-neoplastic process, caused by a cell differentiation failure leading to a cystic transformation, has been discussed, as well as a benign neoplastic lesion. Pancreatic acinar cell cystadenomas usually consist of thin-walled unilocular or multilocular cysts, and mural nodules have been described in two cases of a recent series. In one of these nodules, chromosomal imbalances were detected, which provided preliminary evidence for a neoplastic process. The aim of the current study was to further characterize the lesions by molecular analyses. In four cases without mural nodules, the clonality was assessed by performing mutational analyses within the highly variable displacement-loop region of the mitochondrial DNA. As a result, no closer correlation was identified between different foci within the tumors than between the tumors and adjacent normal pancreatic acinar tissue, indicating polyclonality of these lesions. Further molecular analyses revealed no mutations of the β-catenin and K-ras genes. In addition, no immunohistochemical evidence was identified for mutations of Smad4 or p53. In conclusion, the results of the current study demonstrated that pancreatic acinar cell cystadenomas are non-neoplastic lesions, with the potential exception of those rare cases with mural nodules.
    Oncology letters 08/2014; 8(2):852-858. · 0.99 Impact Factor
    This article is viewable in ResearchGate's enriched format
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background Autoimmune pancreatitis (AIP) is characterized by diffuse or focal swelling of the pancreas. AIP has been divided into types 1 and 2. The aim of the study was to evaluate and compare the clinicopathological characteristics, therapy and outcome of patients with AIP.Methods The medical records of patients diagnosed with AIP between January 2003 and July 2011 were reviewed. Characteristics of patients with AIP types 1 and 2 were compared with those of patients with pancreatic ductal adenocarcinoma (PDAC).ResultsAIP was classified as type 1 in 40 patients and type 2 in 32 according to the HISORt (Histology, Imaging, Serology, Other organ involvement, Response to therapy) criteria. Patients with histologically confirmed AIP type 2 were younger than those with type 1 (P = 0·005). Some 30 of 32 patients with AIP type 2 were found to have a localized tumour-like pancreatic mass and underwent pancreatectomy, compared with only 16 of 40 with type 1 (P < 0·001). Three of 25 patients with AIP type 2 presented with raised serum levels of IgG4 compared with 21 of 38 with type 1 (P < 0·001). There was no difference in symptoms and involvement of other organs between AIP types 1 and 2. Presentation with weight loss was more common among patients with PDAC than those with AIP, but there was no difference in pain or jaundice between the groups. Raised serum carbohydrate antigen 19-9 levels were more prevalent in patients with PDAC.Conclusion Patients with AIP type 2 frequently present with abdominal pain and a tumour-like mass. Differentiating AIP from PDAC is difficult, so making the clinical decision regarding operative versus conservative management is challenging.
    British Journal of Surgery 07/2014; · 4.84 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Lymph node (LN) involvement is a major prognostic factor in pancreatic adenocarcinoma. However, the distinction N0/N1 is not sufficient to accurately predict prognosis. To improve prognostic accuracy in N1 tumors, different LN parameters have been tested. Previous studies were based on series with variable numbers of examined lymph nodes (ELN) and came to inconsistent conclusions as to the value of the number of positive lymph nodes (PLN) and the lymph node ratio (LNR).
    Annals of Surgery 06/2014; · 7.19 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To assess the long-term survival and quality of life in total pancreatectomies and to identify risk factors for perioperative morbidity and mortality.
    Annals of surgery. 06/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: To asses the impact of CA 19-9 and weight loss/gain on outcome after neoadjuvant chemoradiation (CRT) in patients with locally advanced pancreatic cancer (LAPC).
    Annals of Surgical Oncology 06/2014; · 3.94 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To systematically characterize specific pain patterns in the most frequent pancreatic diseases.
    Pancreatology 06/2014; 14(3):S13. · 2.50 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The role of pancreatic acinar cells in initiating necro-inflammatory responses during the early onset of alcoholic acute pancreatitis (AP) has not been fully evaluated. We investigated the ability of acinar cells to generate pro- and anti-inflammatory mediators, including inflammasome-associated IL-18/caspase-1, and evaluated acinar cell necrosis in an animal model of AP and human samples. Rats were fed either an ethanol-containing or control diet for 14 weeks and killed 3 or 24 h after a single lipopolysaccharide (LPS) injection. Inflammasome components and necro-inflammation were evaluated in acinar cells by immunofluorescence (IF), histology, and biochemical approaches. Alcohol exposure enhanced acinar cell-specific production of TNFα, IL-6, MCP-1 and IL-10, as early as 3 h after LPS, whereas IL-18 and caspase-1 were evident 24 h later. Alcohol enhanced LPS-induced TNFα expression, whereas blockade of LPS signaling diminished TNFα production in vitro, indicating that the response of pancreatic acinar cells to LPS is similar to that of immune cells. Similar results were observed from acinar cells in samples from patients with acute/recurrent pancreatitis. Although morphologic examination of sub-clinical AP showed no visible signs of necrosis, early loss of pancreatic HMGB1 and increased systemic levels of HMGB1 and LDH were observed, indicating that this strong systemic inflammatory response is associated with little pancreatic necrosis. These results suggest that TLR-4-positive acinar cells respond to LPS by activating the inflammasome and producing pro- and anti-inflammatory mediators during the development of mild, sub-clinical AP, and that these effects are exacerbated by alcohol injury.
    Cell Death & Disease 10/2013; 4:e816. · 5.18 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The role of pancreatic acinar cells in initiating fibrogenic responses during the early stages of alcoholic acute pancreatitis has not been evaluated. We investigated the ability of injured acinar cells to generate pancreatic fibrosis in acute pancreatitis. Rats were fed either an ethanol-containing or control diet over 14 weeks and euthanized 3 or 24 hours after a single lipopolysaccharide injection. Profibrotic transforming growth factor-β of acinar cells and pancreatic fibrosis were assessed by immunofluorescence, histological characteristics, and electron microscopy. Human pancreatic tissues were also evaluated. Periacinar cell fibrosis and collagen were exacerbated 24 hours after endotoxemia in alcohol-fed rats. Alcohol exposure exacerbated acinar cell-specific production of transforming growth factor β in response to lipopolysaccharide in vivo and in acinar cell-like AR42J cells in vitro. Although a morphological examination showed no visible signs of necrosis, early pancreatic fibrosis can be initiated by little or no pancreatic necrosis. Transforming growth factor β was also significantly increased in human acinar cells from patients with acute/recurrent pancreatitis compared with chronic pancreatitis tissue. Alcohol exacerbates lipopolysaccharide-induced pancreatic fibrosis during the early onset of mild, subclinical, acute pancreatitis. We suggest that multiple, subclinical, acute pancreatitis episodes can accumulate in fibrosis during the development of chronic pancreatitis, even if there is no history of acute pancreatitis.
    American Journal Of Pathology 09/2013; · 4.60 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is usually incurable. Contrary to genetic mechanisms involved in PDAC pathogenesis, epigenetic alterations are ill defined. Here, we determine the contribution of epigenetically silenced genes to the development of PDAC. We analyzed enriched, highly methylated DNAs from PDACs, chronic pancreatitis (CP) and normal tissues using CpG island microarrays and identified WNK2 as a prominent candidate tumor suppressor gene being downregulated early in PDAC development. WNK2 was further investigated in tissue microarrays, methylation analysis of early pancreatic intraepithelial neoplasia (PanIN), mouse models for PDAC and pancreatitis, re-expression studies after demethylation, and cell growth assays using WNK2 overexpression. Demethylation assays confirmed the link between methylation and expression. WNK2 hypermethylation was higher in tumor than in surrounding inflamed tissues and was observed in PanIN lesions as well as in a PDAC mouse model. WNK2 mRNA and protein expressions were lower in PDAC and CP compared with normal tissues both in patients and mouse models. Overexpression of WNK2 led to reduced cell growth, and WNK2 expression in tissues correlated negatively with pERK1/2 expression, a downstream target of WNK2 responsible for cell proliferation. Downregulation of WNK2 by promoter hypermethylation occurs early in PDAC pathogenesis and may support tumor cell growth via the ERK-MAPK pathway.Oncogene advance online publication, 5 August 2013; doi:10.1038/onc.2013.312.
    Oncogene 08/2013; · 8.56 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To evaluate outcome after intensity modulated radiotherapy (IMRT) compared to 3D conformal radiotherapy (3D-RT) as neoadjuvant treatment in patients with locally advanced pancreatic cancer (LAPC). In total, 57 patients with LAPC were treated with IMRT and chemotherapy. A median total dose of 45 Gy to the PTV_baseplan and 54 Gy to the PTV_boost in single doses of 1.8 Gy for the PTV_baseplan and median single doses of 2.2 Gy in the PTV_boost were applied. Outcomes were evaluated and compared to a large cohort of patients treated with 3D-RT. Overall treatment was well tolerated in all patients and IMRT could be completed without interruptions. Median overall survival was 11 months (range 5-37.5 months). Actuarial overall survival at 12 and 24 months was 36 % and 8 %, respectively. A significant impact on overall survival could only be observed for a decrease in CA 19-9 during treatment, patients with less pre-treatment CA 19-9 than the median, as well as weight loss during treatment. Local progression-free survival was 79 % after 6 months, 39 % after 12 months, and 13 % after 24 months. No factors significantly influencing local progression-free survival could be identified. There was no difference in overall and progression-free survival between 3D-RT and IMRT. Secondary resectability was similar in both groups (26 % vs. 28 %). Toxicity was comparable and consisted mainly of hematological toxicity due to chemotherapy. IMRT leads to a comparable outcome compared to 3D-RT in patients with LAPC. In the future, the improved dose distribution, as well as advances in image-guided radiotherapy (IGRT) techniques, may improve the use of IMRT in local dose escalation strategies to potentially improve outcome.
    Strahlentherapie und Onkologie 07/2013; · 2.73 Impact Factor
  • Pancreatology 05/2013; 13(3):S13. · 2.50 Impact Factor
  • Pancreatology 03/2013; 13(2):e28-e29. · 2.50 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND & AIMS: Cancer cells often lose contact inhibition to undergo anchorage-independent proliferation and become resistant to apoptosis by inactivating the Hippo signaling pathway, resulting in activation of the transcriptional co-activator yes-associated protein (YAP). However, the oncogenic mechanisms of YAP are unclear. METHODS: Using cross-species analysis of expression data, the Notch ligand Jagged-1 (Jag-1) was identified as downstream target of YAP in hepatocytes and hepatocellular carcinoma (HCC) cells. We analyzed the functions of YAP in HCC cells via overexpression and RNA silencing experiments. We used transgenic mice that overexpressed a constitutively activated form of YAP (YAP(S127A)), and measured protein levels in HCC and colorectal and pancreatic tumor samples from patients. RESULTS: Human HCC cell lines and mouse hepatocytes that overexpress YAP(S127A) upregulated Jag-1, leading to activation of the Notch pathway and increased proliferation. Induction of Jag-1, activation of Notch, and cell proliferation required binding of YAP to its transcriptional partner TEAD4; TEAD4 binding required Mst1/2, but not WNT-β-catenin signaling. Levels of YAP correlated with Jag-1 expression and Notch signaling in human tumor samples and shorter survival times of patients with HCC or colorectal cancer. CONCLUSION: The transcriptional regulator YAP upregulates Jag-1 to activate Notch signaling in HCC cells and mouse hepatocytes. YAP-dependent activity of Jag-1 and Notch correlate in human HCC and colorectal tumor samples with patient survival times, suggesting the use of YAP and Notch inhibitors as therapeutics for gastrointestinal cancer.
    Gastroenterology 02/2013; · 12.82 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: In the present retrospective analysis we analysed the therapeutic outcome of a set of patients, who were treated with chemoradiation (CRT) for recurrent pancreatic cancer (RPC) in a single institution.Patients and Methods: Forty-one patients had a history of primary resection for pancreatic cancer. In case of an unresectable recurrency patients were treated with CRT at our institution between 2002 and 2010 with a median dose of 48.4 Gy (range 39.6-54 Gy). Concurrent chemotherapy regimes included Gemcitabine (GEM) in 37/41 patients (90%) and Fluorouracil (FU) or Capecitabine (CAP) in 4/41 patients (10%). Patients were re-evaluated after CRT with computed tomography and/or explorative laparotomy. During re-resection or laparotomy 15 patients received an additional intraoperative radiotherapy (IORT) with a median dose of 15 Gy (range 12--15 Gy). Median age was 65 years (range 39--76 years) and there were 26 male and 15 female patients. RESULTS: The median overall survival (mOS), local control (LC) and progression-free survival (PFS) were 16.1, 13.8 and 6.9 months respectively for all patients after the first day of CRT. Re-resection was possible in five patients (12%) and a complete remission (CR) as defined by tumor-free biopsy was seen in 6 patients (15%). When re-resection could be achieved after CRT mOS was improved to 28.3 months (n = 5 patients, 95%-CI 10.2 -- 46.3 months). Patients receiving IORT had a significantly improved mOS compared to no IORT (p = 0.034). Fifteen patients (37%) experienced a local tumour progression and main site of distant metastasis was the liver (11 patients, 27%).Overall treatment-related toxicity was mild, grade III hematologic toxicity was observed in 11 patients (27 %). CONCLUSION: In summary we observed a good therapeutic response with mild to moderate toxicity levels for CRT in RPC. Overall survival and PFS were clearly improved in case of induction of a complete remission (tumor-free biopsies) or after achieving a re-resection, thus providing a curative intended therapy even in case of disease recurrence.
    Radiation Oncology 01/2013; 8(1):27. · 2.36 Impact Factor
    This article is viewable in ResearchGate's enriched format

Publication Stats

2k Citations
470.46 Total Impact Points


  • 2003–2014
    • Universität Heidelberg
      • • Institute of Papyrology
      • • Department of Pathology
      • • Institute of Pathology (Mannheim)
      Heidelburg, Baden-Württemberg, Germany
  • 2008
    • Technische Universität München
      • Clinic and Polyclinic for Surgery
      München, Bavaria, Germany