Christian Wittekind

Publications of Christian Wittekind

• Acoustic radiation force impulse imaging (ARFI) for non-invasive detection of liver fibrosis: examination standards and evaluation of interlobe differences in healthy subjects and chronic liver disease.

  Authors: Thomas Karlas, Cornelia Pfrepper, Johannes Wiegand, Christian Wittekind, Marie Neuschulz, Joachim Mössner, Thomas Berg, Michael Tröltzsch, Volker Keim

  Scandinavian journal of gastroenterology. 09/2011; 46(12):1458-67.

  Acoustic radiation force impulse imaging (ARFI) is a non-invasive method for the quantification of liver stiffness. We aimed to develop standards for the measuring procedure and studied the impact ofAcoustic radiation force impulse imaging (ARFI) is a non-invasive method for the quantification of liver stiffness. We aimed to develop standards for the measuring procedure and studied the impact of different measuring sites. ARFI was tested in a tissue phantom and in 50 healthy volunteers. In addition, 116 patients with chronic liver disease underwent ARFI. The results were compared with histological staging (non-viral liver disease) and transient elastography (hepatitis C). ARFI diagnostic performance was evaluated with receiver operating characteristic curves. ARFI results were not normally distributed in >20% of cases. Deep inspiration significantly increased ARFI values by 13% (p < 0.05). The mean shear-wave velocity in healthy individuals was 1.28 ± 0.19 m/s in the left liver lobe and 1.15 ± 0.17 m/s in the right liver lobe (p < 0.001). Similarly, in 79/116 patients with chronic liver disease a significant difference of shear-wave velocity between both liver lobes was detected. The histological staging correlated with ARFI results of the biopsy site (r = 0.661, p < 0.001) in non-viral liver disease (n = 47). The mean shear-wave velocity in cases with F1 and F2 fibrosis was increased in the left compared with the right liver lobe (2.1 ± 0.73 m/s vs. 1.75 ± 0.89 m/s, p = 0.041). Similar results were obtained in patients with hepatitis C (n = 69). Our study strengthens the necessity for definition of examination standards and demonstrates the usefulness of ARFI in non-viral liver disease. Interlobe variations of liver stiffness demand further investigation.

• Imatinib mesylate for palliative second-line treatment of advanced biliary tract cancer: a bicentric phase II study.

  Authors: Annekathrin Roth, Eberhard Schleyer, Konrad Schoppmeyer, Regine Kluge, Christian Wittekind, Joachim Mössner, Marcus Wiedmann

  Onkologie. 01/2011; 34(8-9):469-70.

• 'Evidence-based medicine: the time has come to set standards for staging'. Is a radical overhaul really needed?

  Authors: Leslie H Sobin, Carolyn A Compton, Mary Gospodarowicz, Frederick L Greene, Leonard L Gunderson, J Milburn Jessup, Christian Wittekind

  The Journal of pathology. 08/2010; 221(4):361-2.

  This Invited Response addresses concerns and opinions expressed in an Invited Commentary, 'Evidence-based medicine: the time has come to set standards for staging', by Quirke et al., published inThis Invited Response addresses concerns and opinions expressed in an Invited Commentary, 'Evidence-based medicine: the time has come to set standards for staging', by Quirke et al., published in this issue of The Journal of Pathology.

• Genetic regulation of serum phytosterol levels and risk of coronary artery disease.

  Authors: Daniel Teupser, Ronny Baber, Uta Ceglarek, Markus Scholz, Thomas Illig, Christian Gieger, Lesca M Holdt, Alexander Leichtle, Karin H Greiser, Dominik Huster [......] Francois Cambien, Stefan Schreiber, Karl Werdan, Thomas Meitinger, Markus Loeffler, Nilesh J Samani, Jeanette Erdmann, H-Erich Wichmann, Heribert Schunkert, Joachim Thiery

  Circulation. Cardiovascular genetics. 08/2010; 3(4):331-9.

  Phytosterols are plant-derived sterols that are taken up from food and can serve as biomarkers of cholesterol uptake. Serum levels are under tight genetic control. We used a genomic approach to studyPhytosterols are plant-derived sterols that are taken up from food and can serve as biomarkers of cholesterol uptake. Serum levels are under tight genetic control. We used a genomic approach to study the molecular regulation of serum phytosterol levels and potential links to coronary artery disease (CAD). A genome-wide association study for serum phytosterols (campesterol, sitosterol, brassicasterol) was conducted in a population-based sample from KORA (Cooperative Research in the Region of Augsburg) (n=1495) with subsequent replication in 2 additional samples (n=1157 and n=1760). Replicated single-nucleotide polymorphisms (SNPs) were tested for association with premature CAD in a metaanalysis of 11 different samples comprising 13 764 CAD cases and 13 630 healthy controls. Genetic variants in the ATP-binding hemitransporter ABCG8 and at the blood group ABO locus were significantly associated with serum phytosterols. Effects in ABCG8 were independently related to SNPs rs4245791 and rs41360247 (combined P=1.6 x 10(-50) and 6.2 x 10(-25), respectively; n=4412). Serum campesterol was elevated 12% for each rs4245791 T-allele. The same allele was associated with 40% decreased hepatic ABCG8 mRNA expression (P=0.009). Effects at the ABO locus were related to SNP rs657152 (combined P=9.4x10(-13)). Alleles of ABCG8 and ABO associated with elevated phytosterol levels displayed significant associations with increased CAD risk (rs4245791 odds ratio, 1.10; 95% CI, 1.06 to 1.14; P=2.2 x 10(-6); rs657152 odds ratio, 1.13; 95% CI, 1.07 to 1.19; P=9.4 x 10(-6)), whereas alleles at ABCG8 associated with reduced phytosterol levels were associated with reduced CAD risk (rs41360247 odds ratio, 0.84; 95% CI, 0.78 to 0.91; P=1.3 x 10(-5)). Common variants in ABCG8 and ABO are strongly associated with serum phytosterol levels and show concordant and previously unknown associations with CAD.

• Assay-based response evaluation in head and neck oncology: requirements for better decision making.

  Authors: Andreas Dietz, Andreas Boehm, Iris-Susanne Horn, Pierre Kruber, Ingo Bechmann, Wojciech Golusinski, Dietger Niederwieser, Ralph Dollner, Torsten W Remmerbach, Christian Wittekind, Stephan Dietzsch, Guido Hildebrandt, Gunnar Wichmann

  European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery. 04/2010; 267(4):483-94.

  This article gives an overview on different current strategies of assay-based response evaluation in head and neck squamous cell carcinomas (HNSCC) and critically summarizes their role and needs forThis article gives an overview on different current strategies of assay-based response evaluation in head and neck squamous cell carcinomas (HNSCC) and critically summarizes their role and needs for future clinical evaluation. Due to a growing amount of data of phase III clinical trials of multimodality treatment options for HNSCC, treatment planning in regard to optimal outcome is becoming an interdisciplinary challenge. New concepts such as induction chemotherapy with bi- or ternary combinations of chemotherapeutics, integration of targeted therapies, concurrent and sequential chemoradiation concepts, and multimodality-based organ preservation strategies strongly compete with traditional definitive surgical procedures. Moreover, the outcome is difficult to predict due to heterogeneity of a tumor's response, impaired late functional outcome, and increased late toxicity if simultaneously applied to radiation. Retrospectively looking at non-responders with tumors classified as resectable, primary surgery is very likely to have achieved better results, since chemoradiation causes a high degree of early and late toxicities leading to extremely complicated terms and conditions in surgery following current multimodal therapeutic strategies. Unfortunately, predictive information on response characteristics of a given tumor before starting the therapy is not available in daily routine, although heterogeneity in response of a given tumor entity to treatments has been known for decades. Therefore, current therapy strategies for HNSCC still have to ignore this fact, creating an urgent need for the development of proper predictive assays. There are interesting clinical observations showing that response on induction chemotherapy may predict the outcome after radiotherapy. Some trials use this empiric phenomenon to pre-select non-responders for primary surgical treatment avoiding severe salvage complications after failure of complete chemoradiation treatment. Moving one step further, recent literature and our own investigations implicate that response evaluation of the individual patient's HNSCC in a suitable ex vivo assay just before starting the treatment is mature for clinical research. To this end, essential needs and hints are addressed and discussed.

• Persistent confusion on the clinical and pathologic nodal staging in lung cancer.

  Authors: Peter Goldstraw, Leslie H Sobin, Christian Wittekind

  Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer. 02/2010; 5(2):286-7.

• Protective Effects of Early CD4(+) T Cell Reduction in Hepatic Ischemia/Reperfusion Injury.

  Authors: Mathias Martin, Christina Mory, Andrea Prescher, Christian Wittekind, Martin Fiedler, Dirk Uhlmann

  Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract. 11/2009;

  AIM: CD4(+) T cells contribute to disturbances of liver microcirculation after warm ischemia/reperfusion (I/R). The aim of this study was to investigate a possible protective role of FTY720AIM: CD4(+) T cells contribute to disturbances of liver microcirculation after warm ischemia/reperfusion (I/R). The aim of this study was to investigate a possible protective role of FTY720 (Sphingosine-1 phosphate receptor agonist) in this setting. MATERIAL AND METHODS: In an in vivo model (42 Wistar rats), ischemia of the left liver lobe was induced for 90 min under anesthesia with xylazine/ketanest. Sham-operated untreated ischemic and treatment group with FTY720 (1 mg/kg body weight intravenous) were investigated. The effect of FTY on I/R injury was assessed by in vivo microscopy 30-90 min after reperfusion (perfusion rate, vessel diameter, leukocyte-endothelial cell interactions, T cell infiltration), by measurement of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), reverse transcription-polymerase chain reaction (RT-PCR) of interleukin (IL)-2, IL-6, IL-10, TNF-alpha, toll-like receptor 4 (TLR-4), and by histological investigation. RESULTS: After 30 min of reperfusion, the number of T cells in sinusoids was increased four-fold. In the FTY group, the number of T cells was reduced to an half of the number of the ischemia group. Likewise, the number of adherent leukocytes in sinusoids (150.8 +/- 10.9% of s.o.) was reduced in the treatment group (117.3 +/- 12.2%; p < 0.05 vs ischemia), leading to an improvement in perfusion rate in this group (85.0 +/- 4.6% of sham group) compared to nontreated animals (57.5 +/- 10.8%; p < 0.05). According to improved microcirculation, AST/ALT values and histological tissue damage were reduced in the therapy group. RT-PCR revealed an increased expression of IL-2, IL-6, and TLR-4 in the nontreated ischemic group. This expression was clearly reduced in the treatment group. CONCLUSION: In conclusion, FTY720 ameliorates the microcirculatory, biochemical, and histological manifestations of hepatic I/R injury by preventing T cell infiltration. These results indicate that T cells are pivotal mediators in hepatic I/R and may have important implications early after liver transplantation and in warm ischemia.

• Budd Chiari syndrome without evidence for thrombosis. Is it still a Budd Chiari ?

  Authors: Sebastian Weis, Christian Wittekind, Christoph Benckert, Joachim Mössner, Henning Wittenburg

  Annals of hepatology : official journal of the Mexican Association of Hepatology. 09/2009; 8(4):388-389.

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• Indocyanine green R15 ratio depends directly on liver perfusion flow rate.

  Authors: Martin Janssen, Karl Druckrey-Fiskaaen, Leyla Omidi, Grzegorz Sliwinski, Christine Thiele, Bernd Donaubauer, Nina Polze, Udo Kaisers, Joachim Thiery, Christian Wittekind, Johann Hauss, Michael Schön

  Journal of hepato-biliary-pancreatic surgery. 09/2009;

  BACKROUND: Indocyanine green (ICG) is a synthetic dye that is widely used to evaluate liver function in critically ill patients, before liver resection or after liver transplantation. ControversyBACKROUND: Indocyanine green (ICG) is a synthetic dye that is widely used to evaluate liver function in critically ill patients, before liver resection or after liver transplantation. Controversy still exists about the impact exerted on the ICG ratio after 15 min (ICG R15) by differences in liver perfusion rates, hyperdynamic states, or patient cardiac output. We studied the role of different liver perfusion rates on the ICG R15 ratio in a normothermic extracorporeal liver perfusion system under standardized conditions. METHODS: Livers from landrace pigs (40-50 kg) were perfused with fresh porcine blood. Normal and high perfusion rates were defined as 1 ml and 2 ml/g liver/min, respectively. Perfusate pressure of the hepatic artery and portal vein were within the physiological range in both groups. According to manufacturer's instructions, 0.5 mg of ICG per kg was applied and the ICG R15 was calculated. Calculations were based on fifteen experiments in five liver perfusions. Bile production, liver function and histology were analyzed. RESULTS: All perfusions were characterized by physiological bile production, lack of hepatocellular damage and normal histology. ICG R15 ratio in group I, perfused with 1 ml/g liver, was 18.9 +/- 6%. In group II, perfused with 2 ml/g liver, the ICG R15 ratio was 7.2 +/- 3%. The difference between groups 1 and 2 was statistically significant (p < 0.05). CONCLUSION: ICG R15 is reliable within one group at defined perfusion rates. Doubled perfusion rates contribute to higher ICG clearance. For clinical application we would like to suggest considering cardiac output of the patient for interpretation of ICG ratios.

• A uniform residual tumor (R) classification: integration of the R classification and the circumferential margin status.

  Authors: Christian Wittekind, Carolyn Compton, Phil Quirke, Iris Nagtegaal, Susanne Merkel, Paul Hermanek, Leslie H Sobin

  Cancer. 06/2009;

  BACKGROUND:: Since the introduction of the TNM residual tumor (R) classification, the involvement of resection margins has been defined either as a microscopic (R1) or a macroscopic (R2)BACKGROUND:: Since the introduction of the TNM residual tumor (R) classification, the involvement of resection margins has been defined either as a microscopic (R1) or a macroscopic (R2) demonstration of tumor directly at the resection margin ("tumor transected"). METHODS:: The recognition of the importance of the circumferential resection margin (CRM) in patients with rectal cancer patients raises the need for an alternative definition of resection margin involvement, namely, the importance of delineating tumor with a minimal distance from the CRM of </=1 mm (CRM-positive) from tumor directly at the resection margin. The different use of both definitions of resection margin involvement prevents valid comparisons between reports on treatment results. RESULTS:: To avoid confusion by different definitions, the authors proposed including the minimal distance between tumor and resection margin into the current R classification. CONCLUSIONS:: By using the proposed expanded classification, comparisons of new data with previous publications will be possible. Cancer 2009. (c) 2009 American Cancer Society.

• Oral Cancer Diagnosis by Mechanical Phenotyping.

  Authors: Torsten W Remmerbach, Falk Wottawah, Julia Dietrich, Bryan Lincoln, Christian Wittekind, Jochen Guck

  Cancer research. 02/2009;

  Oral squamous cell carcinomas are among the 10 most common cancers and have a 50% lethality rate after 5 years. Despite easy access to the oral cavity for cancer screening, the main limitations toOral squamous cell carcinomas are among the 10 most common cancers and have a 50% lethality rate after 5 years. Despite easy access to the oral cavity for cancer screening, the main limitations to successful treatment are uncertain prognostic criteria for (pre-)malignant lesions. Identifying a functional cellular marker may represent a significant improvement for diagnosis and treatment. Toward this goal, mechanical phenotyping of individual cells is a novel approach to detect cytoskeletal changes, which are diagnostic for malignant change. The compliance of cells from cell lines and primary samples of healthy donors and cancer patients was measured using a microfluidic optical stretcher. Cancer cells showed significantly different mechanical behavior, with a higher mean deformability and increased variance. Cancer cells (n approximately 30 cells measured from each patient) were on average 3.5 times more compliant than those of healthy donors [Dnormal = (4.43 +/- 0.68) 10(-3) Pa(-1); Dcancer = (15.8 +/- 1.5) 10(-3) Pa(-1); P < 0.01]. The diagnosis results of the patient samples were confirmed by standard histopathology. The generality of these findings was supported by measurements of two normal and four cancer oral epithelial cell lines. Our results indicate that mechanical phenotyping is a sensible, label-free approach for classifying cancer cells to enable broad screening of suspicious lesions in the oral cavity. It could in principle be applied to any cancer to aid conventional diagnostic procedures. [Cancer Res 2009;69(5):1728-32].

• Ingrowths of a percutaneously implanted aortic valve prosthesis (corevalve) in a patient with severe aortic stenosis.

  Authors: Axel Linke, Robert Höllriegel, Thomas Walther, Katrin Schierle, Christian Wittekind, Jörg Ender, Friedrich W Mohr, Gerhard Schuler

  Circulation. Cardiovascular interventions. 10/2008; 1(2):155-8.

• Experimental treatment of pancreatic cancer with two novel histone deacetylase inhibitors.

  Authors: Martin Haefner, Thilo Bluethner, Manuel Niederhagen, Christian Moebius, Christian Wittekind, Joachim Mossner, Karel Caca, Marcus Wiedmann

  World journal of gastroenterology : WJG. 07/2008; 14(23):3681-92.

  AIM: To investigate in vitro and in vivo treatment with histone deacetylase inhibitors NVP-LAQ824 and NVP-LBH589 in pancreatic cancer. METHODS: Cell-growth inhibition by NVP-LAQ824 and NVP-LBH589 wasAIM: To investigate in vitro and in vivo treatment with histone deacetylase inhibitors NVP-LAQ824 and NVP-LBH589 in pancreatic cancer. METHODS: Cell-growth inhibition by NVP-LAQ824 and NVP-LBH589 was studied in vitro in 8 human pancreatic cancer cell lines using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In addition, the anti-tumoral effect of NVP-LBH589 was studied in a chimeric mouse model. Anti-tumoral activity of the drugs was assessed by immunoblotting for p21(WAF-1), acH4, cell cycle analysis, TUNEL assay, and immunohistochemistry for MIB-1. RESULTS: In vitro treatment with both compounds significantly suppressed the growth of all cancer cell lines and was associated with hyperacetylation of nucleosomal histone H4, increased expression of p21(WAF-1), cell cycle arrest at G2/M-checkpoint, and increased apoptosis. In vivo, NVP-LBH589 alone significantly reduced tumor mass and potentiated the efficacy of gemcitabine. Further analysis of the tumor specimens revealed slightly increased apoptosis and no significant reduction of cell proliferation. CONCLUSION: Our findings suggest that NVP-LBH589 and NVP-LAQ824 are active against human pancreatic cancer, although the precise mechanism of in vivo drug action is not yet completely understood. Therefore, further preclinical and clinical studies for the treatment of pancreatic cancer are recommended.

• Therapeutical concepts and results for klatskin tumors.

  Authors: Helmut Witzigmann, Marcus Wiedmann, Christian Wittekind, Joachim Mössner, Johann Hauss

  Deutsches Ärzteblatt international. 03/2008; 105(9):156-61.

  INTRODUCTION: Most hilar cholangiocarcinomas (Klatskin tumors) are diagnosed at an advanced stage. This article aims to review the literature of resection and palliative treatment in patients withINTRODUCTION: Most hilar cholangiocarcinomas (Klatskin tumors) are diagnosed at an advanced stage. This article aims to review the literature of resection and palliative treatment in patients with hilar cholangiocarcinoma. METHODS: All studies with evidence levels I and II and relevant trials with evidence level III from 1996 to 04/2007 were included. RESULTS: The definition of resectability depends not only on tumor stage but also on operator experience. The best long-term results are achieved by hilar resection combined with extended liver resection. No clear clinical benefit has been demonstrated for neoadjuvant and adjuvant therapies. The role of liver transplantation requires redefinition in view of good long-term survival after neoadjuvant chemoradiation and the possibility of living-donor liver transplantation. Initial studies of a combination of biliary stenting and photodynamic therapy (PDT) for palliation have shown significantly prolonged survival times compared with stenting alone. There is no established standard palliative chemotherapy. DISCUSSION: The prognosis of patients with Klatskin tumors has been significantly improved by extended resection procedures. The combination of stenting and PDT is a useful palliative approach.

• Correlation between beta-catenin mutations and expression of Wnt-signaling target genes in hepatocellular carcinoma.

  Authors: Madeleine Austinat, Ruediger Dunsch, Christian Wittekind, Andrea Tannapfel, Rolf Gebhardt, Frank Gaunitz

  Molecular cancer. 02/2008; 7:21.

  Aberrant Wnt-signaling caused by mutants of beta-catenin, a key regulator of the canonical Wnt-signaling pathway, is frequently detected in cancer. Only recently, it was suggested that inAberrant Wnt-signaling caused by mutants of beta-catenin, a key regulator of the canonical Wnt-signaling pathway, is frequently detected in cancer. Only recently, it was suggested that in hepatocellular carcinoma (HCC) the expression of the target gene glutamine synthetase (GS) is a highly reliable marker for the identification of beta-catenin mutations. In order to prove this hypothesis, 52 samples from human hepatocellular carcinomas were analysed for the activation of beta-catenin and the expression of GS. In total, 45 samples stained positive for cytoplasmic/nuclear beta-catenin. A strong correlation between expression of GS and activated beta-catenin (100% of nuclear and 84% of cytosolic) was found. However, among 35 GS positive tumors that were analysed for beta-catenin mutations no mutations were detected in 25 GS-positive carcinomas although 24 out of the 25 carcinomas exhibited at least abnormal expression of beta-catenin. Since the mutational analysis identified 9 different point mutations of the beta-catenin gene including the rare mutation H36P and the yet unknown mutation P44A it was asked whether these mutations may differently effect beta-catenin target genes. Therefore, expression plasmids for different mutations were constructed and cotransfected with the TOP-flash luciferase reporter and a reporter carrying the GS-5'-enhancer. The experiments confirmed that there are differences between different beta-catenin target sequences and different beta-catenin mutations. In addition, the failure that the endogenous expression of GS in GS-negative cells was not induced by the transient transfection experiment indicated that the effect of beta-catenin on the GS-5'-enhancer is only one aspect of gene activation induced by beta-catenin.

• Correlation between β-catenin mutations and expression of Wnt-signaling target genes in hepatocellular carcinoma

  Authors: Madeleine Austinat, Ruediger Dunsch, Christian Wittekind, Andrea Tannapfel, Rolf Gebhardt, Frank Gaunitz

  Molecular Cancer. 01/2008;

  Abstract Aberrant Wnt-signaling caused by mutants of β-catenin, a key regulator of the canonical Wnt-signaling pathway, is frequently detected in cancer. Only recently, it was suggested that inAbstract Aberrant Wnt-signaling caused by mutants of β-catenin, a key regulator of the canonical Wnt-signaling pathway, is frequently detected in cancer. Only recently, it was suggested that in hepatocellular carcinoma (HCC) the expression of the target gene glutamine synthetase (GS) is a highly reliable marker for the identification of β-catenin mutations. In order to prove this hypothesis, 52 samples from human hepatocellular carcinomas were analysed for the activation of β-catenin and the expression of GS. In total, 45 samples stained positive for cytoplasmic/nuclear β-catenin. A strong correlation between expression of GS and activated β-catenin (100% of nuclear and 84% of cytosolic) was found. However, among 35 GS positive tumors that were analysed for β-catenin mutations no mutations were detected in 25 GS-positive carcinomas although 24 out of the 25 carcinomas exhibited at least abnormal expression of β-catenin. Since the mutational analysis identified 9 different point mutations of the β-catenin gene including the rare mutation H36P and the yet unknown mutation P44A it was asked whether these mutations may differently effect β-catenin target genes. Therefore, expression plasmids for different mutations were constructed and cotransfected with the TOP-flash luciferase reporter and a reporter carrying the GS-5'-enhancer. The experiments confirmed that there are differences between different β-catenin target sequences and different β-catenin mutations. In addition, the failure that the endogenous expression of GS in GS-negative cells was not induced by the transient transfection experiment indicated that the effect of β-catenin on the GS-5'-enhancer is only one aspect of gene activation induced by β-catenin.

• Improvement of multiple sclerosis on tacrolimus plus mycophenolate mofetil after liver transplantation. Clinical improvement of multiple sclerosis in a patient requiring liver transplantation for acute liver failure following interferon-beta therapy.

  Authors: Julia Behrbohm, Matthias Neid, Ulrich Stölzel, Christian Wittekind, Johann P Hauss, Hans L Tillmann

  Transplant international : official journal of the European Society for Organ Transplantation. 01/2008; 20(12):1077-9.

• Signet-ring cell carcinoma arising in the gastric stump after duodenopancreatectomy for ductal adenocarcinoma of the pancreas: a case report.

  Authors: Woubet T Kassahun, Peter Lamesch, Christian Wittekind, Matthias Neid, Jens P Schneider, Joachim Mössner, Johann Hauss

  Clinical medicine. Oncology. 01/2008; 2:109-12.

  The development of malignancy in the gastric stump following surgery for peptic ulcer disease is well recognized. There are also few reports on carcinomas occurring after surgery for malignantThe development of malignancy in the gastric stump following surgery for peptic ulcer disease is well recognized. There are also few reports on carcinomas occurring after surgery for malignant gastric disease. However, carcinoma of the gastric stump after duodenopancreatectomy is extremely rare. We describe what we believe to be an unusual case of signet-ring cell carcinoma of the gastric stump developing at the anastomotic site 5 years after duodenopancreatectomy for ductal adenocarcinoma of the pancreatic head. We performed remnant gastrectomy and Roux-en-Y gastrojejunostomy as a curative resection. This experience clearly underlies that g astric stump carcinoma (GSC) may mimic metastatic disease recurrence leading to diagnostic confusion after surgery for malignancy. Although an increased risk of gastric stump carcinoma after pancreatoduodenectomy for pancreatic cancer has not been established, the possibility of such a complication should be kept in mind when evaluating patients after gastric resection who present with symptoms of metastatic disease recurrence years after the primary operation. Investigations should be independent of the entity of the primary disease or its localization, since GSC may well be amenable to surgical cure as demonstrated in the presented case. Outpatient follow up results of the last four years indicated no recurrence in this case.

• Regenerative capacity differs between micro- and macrovesicular hepatic steatosis.

  Authors: Agnieszka Oleszczuk, Michael Spannbauer, Andrea Tannapfel, Matthias Blüher, Jan Hengstler, Uta-Carolin Pietsch, Annette Schuhmacher, Christian Wittekind, Johann P Hauss, Michael R Schön

  Experimental and toxicologic pathology : official journal of the Gesellschaft für Toxikologische Pathologie. 11/2007; 59(3-4):205-13.

  INTRODUCTION: Independent of etiology, the hepatic microvesicular steatosis has a worse prognosis compared with macrovesicular steatosis. Proliferation compensates for apoptosis and reflectsINTRODUCTION: Independent of etiology, the hepatic microvesicular steatosis has a worse prognosis compared with macrovesicular steatosis. Proliferation compensates for apoptosis and reflects regenerative mechanisms following liver injury. It is unknown whether these two types of fatty liver have differences in regenerative capacity and apoptosis, which could have an impact on their prognosis. METHODS: Two groups of pigs were studied for 72 days under a protein-deficient diet. One group received only protein-deficient diet (n=6), the other was treated in addition to the diet with 6g ethanol/kg/day by means of a percutaneous intragastric catheter (n=6). The rate of proliferating and apoptotic hepatocytes was determined, respectively, by proliferation cell nuclear antigen (PCNA) and ISEL/TUNEL staining for apoptosis in liver biopsies with similar steatosis grade in pigs with micro- or macrovesicular fatty liver. RESULTS: The ethanol-treated group developed microvesicular steatosis, the other group developed macrovesicular steatosis. Proliferation index was significantly increased in macrovesicular in comparison with microvesicular steatosis (p<0.05). Apoptosis rate was similar in both groups. CONCLUSIONS: Regeneration, but not apoptosis rate differs between micro- and macrovesicular steatosis. The reduced regenerative capacity in microvesicular steatosis may contribute to the worse prognosis of this subtype of fatty liver disease.

• Sentinel lymph node biopsy in colon cancer: a prospective multicenter trial.

  Authors: Andreas E Bembenek, Robert Rosenberg, Elke Wagler, Stephan Gretschel, Andreas Sendler, Joerg-Ruediger Siewert, Jörg Nährig, Helmut Witzigmann, Johann Hauss, Christian Knorr [......] Alfred Koenigsrainer, Nikolas H Stoecklein, Olaf Horstmann, Robert Grützmann, Andreas Imdahl, Daniel Svoboda, Christian Wittekind, Wolfgang Schneider, Klaus-Dieter Wernecke, Peter M Schlag

  Annals of surgery. 07/2007; 245(6):858-63.

  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 toINTRODUCTION: 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 < or =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.