Johanna Kirchberg

Carl Gustav Carus-Institut, Pforzheim, Baden-Württemberg, Germany

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Publications (12)23.38 Total impact

  • J. Kirchberg · D. Aust · J. Fritzmann · G. Folprecht · J. Weitz
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    ABSTRACT: Hintergrund Die molekulare Diagnostik hat beim kolorektalen Karzinom (KRK) zur Identifikation von genetisch vorbelasteten Risikopatienten beigetragen. Weiterhin wurden molekulare Marker für besonders gutes oder schlechtes Ansprechen auf zielgerichtete Therapien entdeckt und in die Routinediagnostik implementiert. Methoden Dieser Beitrag beschreibt auf Basis der aktuellen Literatur den Einfluss der molekularen Diagnostik auf Prävention, Diagnosestellung und Therapie beim sporadischen und hereditären KRK. Dabei wird auch ihr Einfluss auf die Planung der chirurgischen Therapie und auf die stratifizierte systemische Antikörpertherapie des KRK dargelegt. Ergebnisse Durch den fehlenden Nachweis der Expression der Mismatch-Repair-Proteine MSH2, PMS2 oder MSH6 kann ein Vorliegen des hereditären Lynch-Syndroms, das in 80 % der Fälle zum KRK führt, als wahrscheinlich angenommen werden. Der molekulare Nachweis einer Mutation des Tumorsuppressorgens APC sichert die Diagnose der familiären adenomatösen Polyposis (FAP), die eine obligate, hereditäre Präkanzerose für das KRK darstellt. In beiden Fällen wird eine genetische Beratung und ggf. ein gezieltes Screening von Angehörigen der betroffenen Patienten eingeleitet. Bei der FAP ist eine restaurative Proktokolektomie mit ileoanaler Pouchanlage, auch prophylaktisch, indiziert. Die Bestimmung des Mutationsstatus des KRAS-Gens ist mittlerweile Standard beim KRK, da nur Patienten mit KRAS-Wildtyp beim metastasierten KRK von einer Therapie mit dem Antikörper gegen den epidermalen Wachstumsfaktorrezeptor (EGFR) Cetuximab profitieren. Schlussfolgerung Die molekulare Diagnostik hat beim KRK wie bei keiner anderen Tumorentität zur Stratifizierung der chirurgischen und systemischen Therapie geführt. Weitere Untersuchungen zur Identifikation von Respondern bzw. Nonrespondern sind wünschenswert.
    03/2015; 30(2):127-133. DOI:10.1007/s12312-015-1299-z
  • C Reißfelder · J Kirchberg · J Weitz
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    ABSTRACT: Aim: The Performance of an oncological low anterior rectum resection with preservation of the sympathic and parasympathic nerves is illustrated. Indication: The total mesorectal excision (TME) by Robert Heald et al. is the gold standard for rectal cancer operations which has lowered drastically the local recurrence rate. As the survival data improve, the new focus is the postoperative quality of life with preserving of the bladder and sexual function. Method: We demonstrate an anterior rectal cancer operation with preserving of the sympathetic and parasympathetic nerves step by step. Conclusion: The critical parts of preserving the nerves with the N. hypogastricus superior and inferior as well as the neurovascular bundle "erigent pillar" are demonstrated.
    Zentralblatt für Chirurgie 08/2014; 139(4):381-3. DOI:10.1055/s-0034-1382905 · 1.05 Impact Factor
  • J Kirchberg · J Weitz
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    ABSTRACT: Initially, mainly superficial liver lesions were resected laparoscopically but now even major resections are performed using a minimally invasive procedure. Careful selection of suitable patients is of key importance. This article describes the current state of the art in patient selection and choice of the appropriate laparoscopic technique based on a review of the recent literature. Perioperative and oncological outcome parameters of laparoscopic liver resection are presented. Laparoscopic liver resection offers significant benefits compared to open liver resection in terms of reduced intraoperative blood loss, reduced overall and liver-specific complications and length of hospital stay without compromising oncological outcomes. Lesions in the peripheral anterolateral segments (segments 2, 3, 4b, 5 and 6) are particularly suitable for laparoscopic liver resection. Access to the posterosuperior segments 1, 4a, 7 and 8 is more challenging but safe and feasible in experienced centers.
    Der Chirurg 07/2014; 85(8). DOI:10.1007/s00104-014-2756-4 · 0.57 Impact Factor
  • Johanna Kirchberg · Christoph Reißfelder · Jürgen Weitz · Moritz Koch
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    ABSTRACT: Despite initial concerns regarding safety and oncological adequacy, the use of laparoscopic liver resections for benign and malignant diseases has spread worldwide. As in open liver surgery, anatomical orientation and the ability to control intraoperative challenges as bleeding have to be combined with expertise in advanced laparoscopic techniques. In this review, we provide an overview regarding the literature on laparoscopic liver resection for benign and malignant liver tumors with the aim to discuss the current standards and define remaining challenges. Although numerous case series and meta-analyses have addressed the evolving field of laparoscopic liver surgery recently, data from randomized controlled trials are still not available. Laparoscopic liver resection is feasible and safe in selected patients and experienced hands. Even major liver resections can be performed laparoscopically. The minimal invasive approach offers benefits in perioperative short-term outcome without compromising oncological outcomes compared to open liver resections. Further randomized trials are needed to formally prove these statements and to define the optimal indication and techniques for the individual patient.
    Langenbeck s Archives of Surgery 09/2013; 398(7). DOI:10.1007/s00423-013-1117-y · 2.19 Impact Factor
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    ABSTRACT: Purpose: Liver regeneration after partial hepatectomy (PH) occurs in conditions of reduced oxygen supply. HIF prolyl hydroxylase enzymes (PHD1, PHD2, and PHD3) are oxygen sensors involved in adaptive response to hypoxia. Specific functions of these PHD enzymes in liver regeneration have, however, remained enigmatic. Here, we investigated the significance of PHD1 in liver regeneration following hepatectomy. Methods: Liver regeneration was studied in PHD1-deficient (PHD1(-/-)) and wild type (WT) mice subjected to 80% hepatectomy. For in vitro analyses, hepatocytes were isolated from PHD1(-/-) and WT livers. Cell cycle progression was studied via FACS-based analysis of nuclear DNA profile. Transcription factor binding assays, qRT-PCR, and immunoblotting were applied to study the relevance of PHD1 downstream effectors during liver regeneration. Results: Liver regeneration was significantly enhanced in PHD1(-/-) mice compared to WT littermates. This effect was due to enhanced proliferation rather than to hypertrophy of liver cells. Cell cycle progression was significantly enhanced, and transcriptional activity of the cell cycle regulator c-Myc was increased in PHD1-deficient hepatocytes. These changes coincided with increased expression of cyclin D2, a cell cycle-promoting c-Myc target, and decreased expression of the cell cycle-delaying c-Myc target p21. Conclusions: Loss of PHD1 enhances liver regeneration by boosting hepatocyte proliferation in a c-Myc-dependent fashion. PHD1 might, therefore, represent a potential target to facilitate liver regeneration after surgical resection.
    Langenbeck s Archives of Surgery 09/2012; 397(8). DOI:10.1007/s00423-012-0998-5 · 2.19 Impact Factor
  • Intensivmedizin up2date 08/2012; 08(03):181-194. DOI:10.1055/s-0032-1310088
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    ABSTRACT: Background Although blood group 0 is associated with a reduced risk of pancreatic cancer, little is known about the role of AB0 blood group antigens in disease progression. We assessed the prognostic relevance of AB0 blood status in a large cohort of patients with resected pancreatic cancer. Methods A total of 627 patients, who underwent resection for pancreatic ductal adenocarcinoma between October 2001 and December 2008 were enrolled. The relationship between AB0 blood group status and outcome was analyzed using univariate and multivariate Cox regression analyses. Results In patients with pancreatic cancer the incidence of blood group 0 (31%) was lower compared to 13.044 patients without pancreatic cancer (38%) (p = 0.0005). There were no significant differences in clinicopathologic characteristics among patients with different AB0 blood groups. The 3-year and 5-year overall survival rates were 29% and 14%. On univariate analysis AB0 blood group status did not correlate with survival (p = 0.39). Multivariate analysis, however, revealed a favorable and independent impact of blood group 0 on survival (Hazard ratio 0.78; 95% confidence interval 0.62 – 0.99; p = 0.037). Conclusion AB0 blood group status is associated independently with the prognosis of patients with resected pancreatic cancer.
    BMC Cancer 07/2012; 12(1):319. DOI:10.1186/1471-2407-12-319 · 3.36 Impact Factor
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    ABSTRACT: Hypoxia and HIFs (HIF-1α and HIF-2α) modulate innate immune responses in the setting of systemic inflammatory responses and sepsis. The HIF prolyl hydroxylase enzymes PHD1, PHD2 and PHD3 regulate the mammalian adaptive response to hypoxia; however, their significance in the innate immune response has not been elucidated. We demonstrate in this study that deficiency of PHD3 (PHD3(-/-)) specifically shortens the survival of mice subjected to various models of abdominal sepsis because of an overwhelming innate immune response, leading to premature organ dysfunction. By contrast, this phenotype was absent in mice deficient for PHD1 (PHD1(-/-)) or PHD2 (PHD2(+/-)). In vivo, plasma levels of proinflammatory cytokines were enhanced, and recruitment of macrophages to internal organs was increased in septic PHD3-deficient mice. Reciprocal bone marrow transplantation in sublethally irradiated mice revealed that enhanced susceptibility of PHD3-deficient mice to sepsis-related lethality was specifically caused by loss of PHD3 in myeloid cells. Several in vitro assays revealed enhanced cytokine production, migration, phagocytic capacity, and proinflammatory activation of PHD3-deficient macrophages. Increased proinflammatory activity of PHD3-deficient macrophages occurred concomitantly with enhanced HIF-1α protein stabilization and increased NF-κB activity, and interference with the expression of HIF-1α or the canonical NF-κB pathway blunted their proinflammatory phenotype. It is concluded that impairment of PHD3 enzyme function aggravates the clinical course of abdominal sepsis via HIF-1α- and NF-κB-mediated enhancement of the innate immune response.
    The Journal of Immunology 07/2012; 189(4):1955-65. DOI:10.4049/jimmunol.1103471 · 4.92 Impact Factor
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    ABSTRACT: Variations in the definition of bile leakage after hepatic resection have prevented the identification of risk factors for early diagnosis and efficient management. The International Study Group of Liver Surgery (ISGLS) definition standardizes reporting of this complication. It was our aim in the present study to prospectively validate the ISGLS definition of bile leakage after hepatic resection. Furthermore, we sought to identify early predictors of clinically relevant bile leakage. A total of 265 patients who underwent elective hepatic resection were enrolled prospectively. Bilirubin concentrations were determined in the serum and drainage fluid until postoperative day 5. Risk factors of Grade B/C bile leakage were assessed by the use of univariate and multivariate analyses. Grade A, B, and C bile leakage was diagnosed in 23 (8.7%), 38 (14.3%), and 11 (4.1%) patients, respectively. The definition as well as severity grading of bile leakage correlated with the duration of drainage and intensive care unit and hospital stay. Perioperative mortality was 0% for Grade A, 5.2% for Grade B, and 45.4% for Grade C bile leakage (P < .0001). Multivariate analysis confirmed bilirubin concentration in the drainage fluid ≥2.4 mg/dL on postoperative day 2 (odds ratio 11.88; 95% confidence interval 5.33-26.49; P < .0001) and anatomic resection (odds ratio 3.59; 95% CI 1.08-11.97; P = .04) as independent predictors of clinically relevant bile leakage. The ISGLS definition and severity grading of bile leakage after hepatic resection is clinically meaningful. Bilirubin concentration in the drainage fluid on postoperative day 2 is a strong predictor of clinically relevant bile leakage.
    Surgery 05/2012; 152(5):821-31. DOI:10.1016/j.surg.2012.03.012 · 3.38 Impact Factor
  • Judit Kiss · Johanna Kirchberg · Martin Schneider
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    ABSTRACT: BACKGROUND: Since mammalian cells rely on the availability of oxygen, they have devised mechanisms to sense environmental oxygen tension, and to efficiently counteract oxygen deprivation (hypoxia). These adaptive responses to hypoxia are essentially mediated by hypoxia inducible transcription factors (HIFs). Three HIF prolyl hydroxylase enzymes (PHD1, PHD2 and PHD3) function as oxygen sensing enzymes, which regulate the activity of HIFs in normoxic and hypoxic conditions. Many of the compensatory functions exerted by the PHD-HIF system are of immediate surgical relevance since they regulate the biological response of ischemic tissues following ligation of blood vessels, of oxygen-deprived inflamed tissues, and of tumors outgrowing their vascular supply. PURPOSE: Here, we outline specific functions of PHD enzymes in surgically relevant pathological conditions, and discuss how these functions might be exploited in order to support the treatment of surgically relevant diseases.
    Langenbeck s Archives of Surgery 03/2012; 397(4):603-10. DOI:10.1007/s00423-012-0930-z · 2.19 Impact Factor
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    ABSTRACT: The tumor edge of colorectal cancer and its adjacent peritumoral tissue is characterized by an invasion front-specific expression of genes that contribute to angiogenesis or epithelial-to-mesenchymal transition. Dysregulation of these genes has a strong impact on the invasion behavior of tumor cells. However, the invasion front-specific expression of microRNA (miRNA) still remains unclear. Therefore, the aim of the present study was to investigate miRNA expression patterns at the invasion front of colorectal liver metastases. Laser microdissection of colorectal liver metastases was performed to obtain separate tissue compartments from the tumor center, tumor invasion front, liver invasion front and pure liver parenchyma. Microarray expression analysis revealed 23 miRNA downregulated in samples from the tumor invasion front with respect to the same miRNA in the liver, the liver invasion front or the tumor center. By comparing samples from the liver invasion front with samples from pure liver parenchyma, the tumor invasion front and the tumor center, 13 miRNA were downregulated. By quantitative RT-PCR, we validated the liver invasion front-specific downregulation of miR-19b, miR-194, let-7b and miR-1275 and the tumor invasion front-specific downregulation of miR-143, miR- 145, let-7b and miR-638. Univariate analysis demonstrated that enhanced expression of miR-19b and miR-194 at the liver invasion front, and decreased expression of let-7 at the tumor invasion front, is an adverse prognostic marker of tumor recurrence and overall survival. In conclusion, the present study suggests that invasion front-specific downregulation of miRNA in colorectal liver metastases plays a pivotal role in tumor progression.
    Cancer Science 07/2011; 102(10):1799-807. DOI:10.1111/j.1349-7006.2011.02023.x · 3.52 Impact Factor
  • Johanna Kirchberg · Katja Ott · Markus Büchler
    Intensivmedizin up2date 01/2010; 6(01):65-77. DOI:10.1055/s-0029-1243811

Publication Stats

87 Citations
23.38 Total Impact Points


  • 2014
    • Carl Gustav Carus-Institut
      Pforzheim, Baden-Württemberg, Germany
  • 2013–2014
    • Technische Universität Dresden
      • Department of Visceral, Thoracic and Vascular Surgery
      Dresden, Saxony, Germany
  • 2011–2012
    • Heidelberg University
      • • Department of General, Visceral and Transplantation Surgery
      • • Department of Spine Surgery
      Heidelburg, Baden-Württemberg, Germany