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1.
J Card Surg ; 37(9): 2747-2749, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35748242

ABSTRACT

Patients suffering retrograde type A aortic dissection after TEVAR for type B dissection are at higher risk of mortality than their spontanous counterparts and the kind of optimal therapy remains obscure. We present a case of successful open surgical repair where distal open anastomosis was accomplished by cutting off the un-covered stent portion and suturing a vascular prosthesis to the dissected distal aortic arch including the covered stent part. The clinical course was regular. Immediate and radical repair in the aortic arch may be the adequate response in such instances.


Subject(s)
Aortic Aneurysm, Thoracic , Aortic Dissection , Blood Vessel Prosthesis Implantation , Endovascular Procedures , Aortic Dissection/etiology , Aorta, Thoracic/diagnostic imaging , Aorta, Thoracic/surgery , Aortic Aneurysm, Thoracic/complications , Blood Vessel Prosthesis/adverse effects , Blood Vessel Prosthesis Implantation/methods , Endovascular Procedures/methods , Humans , Middle Aged , Retrospective Studies , Stents/adverse effects , Treatment Outcome
2.
J Heart Valve Dis ; 26(5): 613-615, 2017 09.
Article in English | MEDLINE | ID: mdl-29762937

ABSTRACT

Over the years, the surgery of ventricular postinfarction aneurysm has evolved from linear resection to endoaneurysmorrhaphy using a patch. Technically, several aims that include the restoration of ventricular shape and function, exclusion of dead space, minimization of the risk of thrombus formation and restoration of valve function are pursued. Herein is reported the case of a 58-year-old male with a giant inferobasal aneurysm involving the mitral valve apparatus who underwent successful endoaneurysmorrhaphy. Correct sizing of the patch proved to be the 'road to success' in this patient. The present case is the second reported instance of a giant ventricular aneurysm involving the mitral valve, with favorable outcome.


Subject(s)
Cardiac Surgical Procedures/methods , Heart Aneurysm , Heart Ventricles , Mitral Valve Insufficiency , Thrombosis/prevention & control , Heart Aneurysm/complications , Heart Aneurysm/diagnosis , Heart Aneurysm/physiopathology , Heart Aneurysm/surgery , Heart Ventricles/diagnostic imaging , Heart Ventricles/pathology , Heart Ventricles/physiopathology , Heart Ventricles/surgery , Humans , Male , Middle Aged , Mitral Valve Insufficiency/diagnosis , Mitral Valve Insufficiency/etiology , Mitral Valve Insufficiency/surgery , Severity of Illness Index , Thrombosis/etiology , Treatment Outcome
3.
J Heart Valve Dis ; 23(1): 9-16, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24779323

ABSTRACT

BACKGROUND AND AIM OF THE STUDY: The benefit of valve-sparing aortic root replacement compared to conventional aortic root replacement surgery remains unclear. METHODS: Between February 2009 and November 2010, a total of 112 patients underwent aortic root surgery at the Department of Cardiovascular and Thoracic Surgery, Heinrich-Heine-University, Dusseldorf, Germany. The valve-sparing technique was used when leaflets were grossly normal. In cases where the valve could not be saved, a prosthetic or biological substitute was used for the aortic root, according to existing guidelines. The patients were allocated to three groups: (i) valve-sparing aortic root replacement group using the David technique (VSR-David; n = 47); (ii) valve-replacing aortic root surgery with a prosthetic conduit using the Bentall-Kuchucus technique (VRR-Prosthetic; n = 31); and (iii) valve-replacing aortic root surgery with a biological stentless valve with the full root technique (VRR-Bio; n = 34). RESULTS: Intraoperative data revealed that, in the VSR-David group, the cardiopulmonary bypass and cross-clamp times were significantly longer (207 +/- 68 min and 140 +/- 38 min respectively; both p = 0.001). The VRR-Prosthetic patients were at highest risk (mean EuroSCORE 15.9%) compared to the VSR-David and VRR-Bio groups (10.8% and 10.4%, respectively). Postoperative analysis showed that patients in the VRR-Bio group had the lowest number of perioperative heart failures (p = 0.004). The perioperative 30-day mortality was significantly higher in the VRR-Prosthetic group (22.6%; p = 0.004). Transaortic flow velocities were significantly lower in the VSR-David group, followed by the VRR-Bio group and VRR-Prosthetic group (1.66 +/- 0.54, 1.98 +/- 0.45, and 2.29 +/- 0.39 m/s, respectively; p = 0.012). The univariate and multivariate analyses of perioperative risk factors showed that only open distal anastomosis was strongly associated with negative results, but not the valve-sparing technique. CONCLUSION: Aortic valve-sparing root replacement must be considered as an excellent alternative for young patients requiring aortic root replacement when a biological valve is clinically indicated. For patients aged >65 years, or with a decreased life expectancy, the full root technique with a stentless valve should be used, given its technical simplicity and excellent postoperative results.


Subject(s)
Aortic Valve/surgery , Heart Defects, Congenital/mortality , Heart Defects, Congenital/surgery , Heart Valve Diseases/mortality , Heart Valve Diseases/surgery , Heart Valve Prosthesis Implantation/methods , Aged , Anastomosis, Surgical/methods , Bicuspid Aortic Valve Disease , Bioprosthesis , Blood Flow Velocity , Cardiopulmonary Bypass , Female , Heart Valve Prosthesis , Humans , Length of Stay , Male , Middle Aged , Multivariate Analysis , Operative Time , Organ Sparing Treatments , Prospective Studies , Severity of Illness Index
4.
Eur J Cardiothorac Surg ; 44(1): 178-9, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23562939

ABSTRACT

Transfemoral stent graft implantation in the ascending aorta has been performed in patients with aortic abnormalities and particularly in the case of an existing symptomatic thrombus. We report on a 68-year old male patient who presented to our clinic with angina-pectoris-like chest pain after having been treated with an aortic stent graft. A computed tomography scan revealed a thrombus in the left main stem that could be successfully removed. The aortic stent graft was removed and the supracoronary ascending aorta replaced.


Subject(s)
Aorta , Coronary Sinus , Coronary Thrombosis , Endovascular Procedures , Thoracotomy , Aged , Aorta/pathology , Aorta/surgery , Blood Vessel Prosthesis Implantation/methods , Coronary Sinus/pathology , Coronary Sinus/physiopathology , Coronary Thrombosis/pathology , Coronary Thrombosis/surgery , Humans , Male , Reoperation , Stents , Tomography, X-Ray Computed
5.
Thorac Cardiovasc Surg ; 61(6): 541-2, 2013 Sep.
Article in English | MEDLINE | ID: mdl-22215504

ABSTRACT

In a 43-year-old female, Ross operation was performed with annular reinforcement of the autograft and a cryo-fixed homograft that proved to be contaminated with enterobacter cloacae and klebsiella pneumoniae at the time of operation. Clinical course was unremarkable, perhaps due to effective antibiotic prophylaxis and treatment. In the literature, little is known about intraoperative bacterial contamination and early endocarditis. The authors report what they believe is the second reported case. Particular resistibilities of homograft and autograft might make early endocarditis unlikely.


Subject(s)
Endocarditis, Bacterial/microbiology , Enterobacter cloacae/isolation & purification , Enterobacteriaceae Infections/microbiology , Heart Valve Prosthesis Implantation/adverse effects , Heart Valve Prosthesis/adverse effects , Klebsiella Infections/microbiology , Klebsiella pneumoniae/isolation & purification , Prosthesis-Related Infections/microbiology , Pulmonary Valve/transplantation , Adult , Allografts , Anti-Bacterial Agents/therapeutic use , Aortic Valve/abnormalities , Aortic Valve/surgery , Aortic Valve Stenosis/diagnosis , Aortic Valve Stenosis/surgery , Bicuspid Aortic Valve Disease , Drug Therapy, Combination , Endocarditis, Bacterial/diagnosis , Endocarditis, Bacterial/drug therapy , Enterobacter cloacae/drug effects , Enterobacteriaceae Infections/diagnosis , Enterobacteriaceae Infections/drug therapy , Female , Heart Valve Diseases/diagnosis , Heart Valve Diseases/surgery , Heart Valve Prosthesis Implantation/instrumentation , Humans , Klebsiella Infections/diagnosis , Klebsiella Infections/drug therapy , Klebsiella pneumoniae/drug effects , Microbial Sensitivity Tests , Prosthesis-Related Infections/diagnosis , Prosthesis-Related Infections/drug therapy , Treatment Outcome
7.
J Surg Res ; 169(1): 31-5, 2011 Jul.
Article in English | MEDLINE | ID: mdl-20417938

ABSTRACT

BACKGROUND: Patients with gastrointestinal stromal tumors (GIST) harbor increased levels of circulating tumor DNA in their peripheral blood. In the current study, the aim was to investigate whether the frequency of loss of heterozygosity (LOH) on cell-free DNA in blood may reflect tumor stage and recurrent disease of these patients. MATERIALS AND METHODS: Serum DNA and follow-up samples of 92 patients suffering from recurrent GIST were analyzed by a PCR-based fluorescence microsatellite analysis using a panel of 12 polymorphic markers. The data were correlated with established risk factors, and patients were followed-up over 4 y. RESULTS: Microsatellite analysis demonstrated a positive LOH score on cell-free DNA of 30/92 patients. A significant correlation with recurrence in CT imaging showed that a positive LOH score (n ≥ 2) was detected in 58% (11/19) of patients with recurrent disease (P = 0.030, χ(2) test), but only in 25% of patients were clinically free of recurrence. No prognostic significance of a positive LOH score was observed after a median observation time of 48 mo. CONCLUSION: Our findings show that LOH on circulating serum DNA correlates with the tumor status and is a frequent event in GIST patients with recurrent disease.


Subject(s)
DNA, Neoplasm/blood , DNA, Neoplasm/genetics , Gastrointestinal Stromal Tumors/blood , Loss of Heterozygosity/genetics , Microsatellite Repeats/genetics , Neoplasm Recurrence, Local/diagnosis , Biomarkers, Tumor/blood , Disease Progression , Female , Follow-Up Studies , Gastrointestinal Stromal Tumors/diagnostic imaging , Gastrointestinal Stromal Tumors/genetics , Humans , Longitudinal Studies , Male , Middle Aged , Neoplasm Recurrence, Local/blood , Neoplasm Recurrence, Local/genetics , Predictive Value of Tests , Prognosis , Retrospective Studies , Tomography, X-Ray Computed
8.
J Card Surg ; 26(1): 22-7, 2011 Jan.
Article in English | MEDLINE | ID: mdl-21073533

ABSTRACT

BACKGROUND: Maintenance of an open sternotomy (OS) after a complicated cardiac operation is an adjunct in the treatment of the severely impaired heart. The purpose of this retrospective study was to evaluate the incidence, survival, and predictors of poor outcome for open chest management (OCM) with delayed sternal closure (DSC) at our department. METHODS: Prolonged open chest (OC) was used in 179 of 5122 cardiac surgery patients between 2004 and 2008 (3.5%). We wanted to determine indications, mortality, postoperative complications, and predictors of outcome. RESULTS: The incidence of OS was 3.5%, with 1.3% for isolated CABG, 2.4% for isolated valve, and 6.4% for combined procedures. Indications for OS were: hemodynamic compromise (110), intractable bleeding (19), arrhythmia (14), and cardiac edema or tamponade (36). 127 of the 179 patients with DSC (71%) survived. 52 patients died: 20 before DSC and 32 after this procedure. Mortality could be related to the indication for OS: With the indication "low cardiac output syndrome" (LCOS) the mortality was 34.5%, for bleeding it was 26.3%, for arrhythmias, 21.4%, and for tamponade on closure it was 16.7%. After DSC, deep sternal wound infection occurred in nine patients (5%), superficial infection in 4.7% of patients. There were 16 patients with postoperative stroke (8.9%) and 24 patients with need for dialysis (13.4%). Predictors of mortality by univariate analysis were VAD insertion, new onset of hemodialysis, reoperation for bleeding, mean length of duration of OS (survivors 3.4 days, nonsurvivors 6.5 days), and longer duration of high-dose inotropic therapy. CONCLUSION: This study shows that OCM with DSC is a beneficial, therapeutic option in patients with postoperative LCOS, significant hemorrhage or intractable arrhythmias. However, patients with reoperation for bleeding, need for VAD, and particularly a prolonged delay before sternal closure continued to have a poor outcome.


Subject(s)
Cardiac Surgical Procedures/mortality , Cardiac Surgical Procedures/methods , Sternum/surgery , Aged , Arrhythmias, Cardiac , Blood Loss, Surgical , Cardiac Output, Low , Female , Humans , Male , Postoperative Complications , Prognosis , Retrospective Studies , Treatment Outcome
9.
Acta Cardiol ; 65(4): 441-7, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20821937

ABSTRACT

BACKGROUND: The benefit of concomitant mitral valve correction (replacement or reconstruction, MVR) and coronary artery bypass grafting (CABG) in patients with coronary artery disease and mitral regurgitation (MR) remains unclear. PATIENTS AND METHODS: 298 consecutive patients underwent CABG alone (n=196) or CABG+ MVR (n=102) between January 2003 and April 2008. Clinical data were collected and MR graded according to preoperative echocardiographic studies. Four severity grades of MR were determined and patients assigned accordingly. Echocardiographic follow-up was performed postoperatively to assess heart and valve function. Multivariate logistic regression analysis was performed for perioperative morbidity and mortality. RESULTS: Patients were comparable within the groups regarding age, gender, NYHA-class, ejection fraction and number of graft vessels. Perioperative mortality (10.8% vs. 5.1%, P < 0.05) and degree of MR were higher among CABG+MVR patients. Among patients with moderate to severe or severe MR, postoperative echocardiography showed an improvement of mitral regurgitation in 95% of CABG+MVR and in 64% of CABG only patients. In patients with mild or moderate MR, improvement rates of both groups were similar (74% and 69%, respectively). Postoperatively, ejection fraction increased in both groups (CABG+MVR: 31.3 +/- 8.5 to 36.4 +/- 11.2; CABG only: 29.9 +/- 6.1 to 33.3 +/- 8.1, P > 0.05). Significant predictors for peri-operative mortality were renal insufficiency, older age and NYHA class III/IV. CONCLUSIONS: For reduction of ischaemic MR, CABG+MVR is preferable in patients with moderate to severe or severe MR. Combined CABG+MVR procedures cannot be recommended for patients with a particular risk profile because of disproportionately high peri-operative mortality.


Subject(s)
Coronary Artery Bypass , Coronary Disease/surgery , Mitral Valve Insufficiency/surgery , Age Factors , Aged , Chi-Square Distribution , Coronary Disease/complications , Coronary Disease/diagnostic imaging , Echocardiography , Female , Humans , Logistic Models , Male , Mitral Valve Insufficiency/complications , Mitral Valve Insufficiency/diagnostic imaging , Predictive Value of Tests , Renal Insufficiency/complications , Retrospective Studies , Risk Factors , Treatment Outcome
11.
Int J Cancer ; 126(11): 2671-81, 2010 Jun 01.
Article in English | MEDLINE | ID: mdl-19847813

ABSTRACT

We describe the development of an aggressive orthotopic metastatic model of esophageal cancer, which is visualized in real time with combined magnetic resonance imaging (MRI) and fluorescence imaging. The aim of the study was to describe the development of a novel model of metastatic tumor disease of esophageal carcinoma and use this model to evaluate fluorescence and MRI in early detection of local and metastatic disease. The human esophageal adenocarcinoma cell line PT1590 was stably transfected with green fluorescent protein (GFP). Nude mice were orthotopically implanted with PT1590-GFP cells. Orthotopic tumor growth as well as metastatic spread was examined by fluorescence imaging and high-resolution MRI at defined intervals after orthotopic implantation. Highly aggressive novel fluorescent cell lines were isolated from metastatic tissues and put into culture. After implantation of these cells, 100% of the animals developed orthotopic primary tumors. In 83% of animals, metastatic spread to liver, lung and lymph nodes was observed. Primary tumor growth could be visualized with fluorescence imaging and with MRI with high correlation between the 2 methods. Fluorescence imaging allows fast, sensitive, and economical imaging of the primary and metastatic tumor without anesthesia. With MRI, anatomical structures are visualized more precisely and tumors can be more accurately localized to specific organs. This model should prove highly useful to understand esophageal carcinoma and to identify novel therapeutics for this treatment-resistant disease.


Subject(s)
Esophageal Neoplasms/pathology , Adenocarcinoma/pathology , Animals , Cell Line, Tumor , Disease Models, Animal , Esophageal Neoplasms/mortality , Green Fluorescent Proteins/analysis , Green Fluorescent Proteins/genetics , Humans , Magnetic Resonance Imaging , Mice , Neoplasm Metastasis/pathology , Spectrometry, Fluorescence , Survival Analysis , Transfection
12.
Dig Surg ; 26(3): 229-35, 2009.
Article in English | MEDLINE | ID: mdl-19468233

ABSTRACT

PURPOSE: Recurrence of a gastrointestinal stromal tumor (GIST) may require multimodal therapy and the role of repeated surgery in this concept is unclear. PATIENTS AND METHODS: A consecutive series of GIST patients treated by surgery, imatinib therapy or both was retrospectively reviewed, and long-term survival was studied by Kaplan-Meier analysis. RESULTS: Institutional primary surgeries before 1999 necessitated reclassification of the histopathological sections and 58/78 patients were classified as having true GIST. In primary surgeries, liver metastases were observed in GIST (6/58) but not in sarcoma/schwannoma patients (0/20), and exulceration of the primary tumor did not correlate with adverse outcome. Additionally, 86 patients were seen on an outpatient basis or were treated for recurrence at our institution, thus a total of 144 GIST patients were seen at our institution between 1994 and 2007 for either primary or secondary tumor manifestation. After 2003, 19/144 GISTs recurred and were treated by targeted therapy with imatinib. The patients showed better overall survival than historic controls. Imatinib therapy enhanced re-resectability due to tumor downsizing, and re-resection (n = 16) improved survival significantly (p = 0.046, log-rank test). CONCLUSION: A multimodal approach including targeted therapy and repeated surgery in the long-term management of recurrent GIST improves survival.


Subject(s)
Gastrointestinal Stromal Tumors/surgery , Leiomyoma/surgery , Leiomyosarcoma/surgery , Neoplasm Recurrence, Local/surgery , Neurilemmoma/surgery , Reoperation , Antineoplastic Agents/therapeutic use , Benzamides , Clinical Protocols , Combined Modality Therapy , Female , Gastrointestinal Stromal Tumors/mortality , Gastrointestinal Stromal Tumors/pathology , Humans , Imatinib Mesylate , Kaplan-Meier Estimate , Leiomyoma/pathology , Leiomyosarcoma/pathology , Longitudinal Studies , Male , Middle Aged , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/pathology , Neurilemmoma/pathology , Piperazines/therapeutic use , Pyrimidines/therapeutic use , Retrospective Studies , Treatment Outcome
13.
Anticancer Res ; 29(4): 1195-9, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19414364

ABSTRACT

BACKGROUND: Esophageal adenocarcinoma is currently the most rapidly increasing cancer in Western populations. L1 (CD171), a neural cell adhesion molecule, has an essential function in tumor progression and has been shown to be expressed in the proliferating cells of the intestinal crypts in mice. The aim of the current study was to determine L1 expression in esophageal cancer and to evaluate whether L1 could serve as a potential marker and therapeutic target for this tumor type. MATERIALS AND METHODS: L1 expression was assessed on a tissue microarray with 257 surgically resected esophageal cancer samples by immunohistochemistry with a monoclonal antibody (Clone UJ127). L1 expression was correlated with clinicopathological data. RESULTS: L1 was detected in 22 (9%) of 257 esophageal cases, whereas 235 (91%) were L1 negative. Nineteen (86%) of the 22 L1-positive cases were adenocarcinoma. Cross table analysis showed a significant association between L1 expression and adenocarcinoma subtype (p<0.001), but not squamous cell carcinoma. CONCLUSION: L1 expression in a subgroup of esophageal cancer is specifically prevalent in adenocarcinoma. Data suggest L1 as a potential target for biological therapy in L1-positive esophageal adenocarcinoma patients.


Subject(s)
Adenocarcinoma/metabolism , Biomarkers, Tumor/metabolism , Carcinoma, Squamous Cell/metabolism , Esophageal Neoplasms/metabolism , Neural Cell Adhesion Molecule L1/metabolism , Adenocarcinoma/secondary , Carcinoma, Squamous Cell/secondary , Esophageal Neoplasms/pathology , Female , Humans , Immunoenzyme Techniques , Male , Middle Aged , Prognosis , Retrospective Studies , Survival Rate , Tissue Array Analysis
14.
Surgery ; 145(4): 392-8, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19303987

ABSTRACT

BACKGROUND: Myasthenia gravis (MG) is an autoimmune disease with a tremendous impact on the quality of life. Controversies over which patients should be operated on because they may benefit most from thymectomy are still ongoing. The aim of this study was to report our long-term results of patients with MG with comparison of thymectomy and conservative treatment. METHODS: We report a series of 252 patients with MG. Survival data were generated. Patients were seen in the outpatient clinic, where a modified Osserman score and quality of life score were evaluated at the end of the follow-up period for all surviving patients. RESULTS: A total of 172 patients with MG were followed after thymectomy or with conservative treatment for a median time of 9.8 years. Patients who underwent thymectomy had significantly greater rates of remission and improvement compared with conservative treatment. Furthermore, they had a significantly greater survival. CONCLUSION: Currently, different effective modalities of treatment are available in patients with MG. In our long-term follow-up, thymectomy was superior to conservative treatment regarding overall survival, clinical improvement, and remission rate. Therefore, thymectomy should be considered strongly for all patients with generalized MG.


Subject(s)
Myasthenia Gravis/surgery , Quality of Life , Thymectomy , Adolescent , Adult , Aged , Aged, 80 and over , Child , Female , Germany/epidemiology , Humans , Male , Middle Aged , Myasthenia Gravis/diagnosis , Myasthenia Gravis/mortality , Treatment Outcome , Young Adult
15.
Histol Histopathol ; 24(5): 551-7, 2009 05.
Article in English | MEDLINE | ID: mdl-19283663

ABSTRACT

Inflammatory cytokines have been shown to mediate organ damage by their action on vascular endothelia and leukocytes, in part by upregulating the expression of adhesion molecules, which in turn convey transmigration of leukocytes into tissue. The upregulation and activation of vascular cell adhesion molecules on the endothelial cells avail firm leukocyte adhesion to the vascular endothelium and enhance their transmigration and consecutive tissue injury. The aim of this study was to evaluate the expression of vascular adhesion molecules CD 31 (PECAM-1), CD 106 (VCAM-1), CD 62E (E-Selectin) and CD 62P (P-Selectin) in the pancreas and distant organs of pigs suffering from acute necrotizing pancreatitis (AP). AP was induced in 13 pigs by a combination of intravenous cerulein and intraductal glycodeoxycholic acid. For immunostaining of vascular adhesion molecules slides of porcine pancreas, lung, kidney and liver tissue were stained with monoclonal antibodies (Ab) against PECAM-1-1, VCAM-1 E- and P- SELECTIN. The endothelial cell expression of CD 31 (PECAM-1), CD 106 (VCAM), CD 62E (E-Selectin) and CD 62P (P-SELECTIN) in severe porcine pancreatitis is detectable and upregulation is partly significantly.


Subject(s)
E-Selectin/physiology , P-Selectin/physiology , Pancreatitis, Acute Necrotizing/etiology , Pancreatitis, Acute Necrotizing/physiopathology , Platelet Endothelial Cell Adhesion Molecule-1/physiology , Vascular Cell Adhesion Molecule-1/physiology , Animals , Cell Adhesion/physiology , Cell Movement/physiology , Endothelial Cells/physiology , Immunohistochemistry , Inflammation Mediators/physiology , Kidney/physiopathology , Leukocytes/physiology , Liver/physiology , Lung/physiopathology , Pancreas/physiopathology , Swine , Up-Regulation
16.
Histopathology ; 54(3): 303-8, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19236506

ABSTRACT

AIMS: Gastrointestinal stromal tumours (GISTs) display genetic alterations on chromosome 22. GTn repeat (GTn) length polymorphism in the promoter of haeme oxygenase-1 gene (HMOX-1) is located on chromosome 22 and associated with malignant growth. The aim was to investigate the role of HMOX-1 promoter polymorphism in GIST patients. METHODS AND RESULTS: Tumour and corresponding healthy tissue DNA of 44 patients who underwent surgical resection of GIST were analysed by polymerase chain reaction, capillary electrophoresis and DNA sequencing. GTn polymorphism was classified into short (S) and long (L) allele. There was no difference detected in GTn genotype between tumour and healthy tissue DNA. Short GTn allele (SGTn) was significantly associated with metastatic disease, higher tumour recurrence rates and high risk GIST (consensus criteria 2001). Furthermore, SGTn allele carriers had significantly shorter disease-free and overall survival (log rank test, P < 0.0001). On multivariate Cox regression analysis, GTn polymorphism was identified as an independent prognostic factor for survival (P = 0.001). CONCLUSIONS: HMOX-1 promoter GTn polymorphism is a potential prognostic marker and may help to allocate patients to different risk groups, customized therapy and follow-up. Haeme oxygenase-1 could represent an important candidate gene in the pathogenesis and growth of GIST.


Subject(s)
Biomarkers, Tumor/genetics , Gastrointestinal Stromal Tumors/genetics , Heme Oxygenase-1/genetics , Polymorphism, Genetic , Promoter Regions, Genetic/genetics , Biomarkers, Tumor/metabolism , Female , Gastrointestinal Stromal Tumors/enzymology , Gastrointestinal Stromal Tumors/pathology , Heme Oxygenase-1/metabolism , Humans , Male , Middle Aged
17.
J Clin Gastroenterol ; 43(1): 27-35, 2009 Jan.
Article in English | MEDLINE | ID: mdl-18469721

ABSTRACT

GOALS: To study the role of loss of heterozygosity (LOH) in serum microsatellite DNA of patients with gastrointestinal stromal tumors (GIST). BACKGROUND: In GIST, tumor markers from peripheral blood are missing. STUDY: Seventy-eight patients (59 GIST, 13 leiomyomas, 2 leiomyosarcomas, and 4 schwannomas) underwent resection at our institute between 1985 and 2006. Thirty-three preoperative sera (26 GIST and 7 non-GIST) and 62 postoperative sera (47 GIST and 15 non-GIST) were available and tested for alterations in 12 representative microsatellite loci on chromosomes 22, 17, 13, 9, and 3, using fluorescence-based automated capillary electrophoresis by ABI Prism. Survival was calculated with Kaplan-Meier plots. RESULTS: Seventeen out of 26 GIST patients had a positive preoperative serum LOH score (> or =2 LOH, sensitivity 65.4%), and 6 out of 7 non-GIST patients had a negative score (< or =1 LOH, specificity 85.7%, P=0.030, Fisher exact test). Serum LOH in GIST were strongly correlated with Fletcher risk groups (P=0.016, chi test). All metastasized GIST (7/7) showed > or =2 LOH preoperatively. Postoperative sensitivity and specificity of LOH analysis for prediction of relapse in 47 GIST was 75.0% and 64.1%, respectively. After a median observation time of 51.3 months (95% confidence interval, 39.4-61.4), LOH in serum significantly predicted overall survival (P=0.007, log-rank test). CONCLUSIONS: LOH serum analysis in GIST may play a role as a noninvasive, differential diagnostic, prognostic, and monitoring marker in the clinical routine.


Subject(s)
DNA, Neoplasm/genetics , Gastrointestinal Stromal Tumors/genetics , Loss of Heterozygosity/genetics , Microsatellite Repeats/genetics , Biomarkers, Tumor/blood , Diagnosis, Differential , Female , Follow-Up Studies , Gastrointestinal Stromal Tumors/diagnosis , Gastrointestinal Stromal Tumors/mortality , Humans , Kaplan-Meier Estimate , Leiomyoma/diagnosis , Leiomyoma/genetics , Leiomyosarcoma/diagnosis , Leiomyosarcoma/genetics , Male , Middle Aged , Neoplasm Recurrence, Local , Neurilemmoma/diagnosis , Neurilemmoma/genetics , Predictive Value of Tests , Sensitivity and Specificity , Survival Rate , Time Factors
18.
J Gastrointest Surg ; 13(2): 181-7, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19052822

ABSTRACT

BACKGROUND: Esophageal cancer is one of the most frequent cancers worldwide and is associated with poor outcome. Besides clinicopathological data, few prognostic molecular markers exist. Esophageal-cancer-related gene1 (ECRG1) short tandem repeats are associated with higher risk for developing esophageal squamous cell carcinoma. The aim of the present study was to evaluate the impact of DNA polymorphisms in the coding region of ECRG1 in esophageal carcinoma. METHODS: Genomic DNA of 107 patients with esophageal cancer that underwent complete surgical resection between 1997 and 2005 was extracted. DNA was analyzed for ECRG1 polymorphisms Arg290Arg, Arg290Gln, and Gln290Gln by PCR and gel electrophoresis. Polymorphisms were correlated with survival data by the Kaplan-Meier method, multivariate Cox regression analysis, and odds ratio were determined. For all variables, cross tables were generated, followed by calculation of the p value by using the chi-square test/Fisher-exact test. RESULTS: Follow-up data of 102 patients with esophageal cancer were available after complete surgical resection for a median follow-up time of 24.3 months. Polymorphism Arg290Arg was found in 47 patients (46.1%), Arg290Gln in 48 patients (47.0%), and Gln290Gln in seven cases (6.9%). Arg290Arg polymorphism was significantly associated with reduced overall survival (p = 0.01) and tumor-free survival (p = 0.01) by the log-rank test. Multivariate regression analysis by Cox revealed polymorphism Arg290Arg to be a significant prognostic factor for survival (p = 0.012). CONCLUSIONS: Polymorphism Arg290Arg in ECRG1 is associated with poor clinical outcome after complete surgical resection in patients with esophageal cancer.


Subject(s)
Adenocarcinoma/genetics , Carcinoma, Squamous Cell/genetics , Esophageal Neoplasms/genetics , Esophageal Neoplasms/mortality , Polymorphism, Genetic/genetics , Recombinant Fusion Proteins/genetics , Adenocarcinoma/mortality , Adenocarcinoma/surgery , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/surgery , Cohort Studies , Esophageal Neoplasms/surgery , Female , Humans , Male , Membrane Proteins , Microsatellite Repeats/genetics , Middle Aged , Predictive Value of Tests , Risk Factors , Serine Proteases , Survival Rate , Treatment Outcome
19.
J Gastrointest Surg ; 12(11): 1830-7; discussion 1837-8, 2008 Nov.
Article in English | MEDLINE | ID: mdl-18791769

ABSTRACT

BACKGROUND: To assess the prognostic significance of nodal microinvolvement in patients with carcinoma of the papilla of Vater. METHODS: From 1993 to 2003 at the University Clinic Hamburg, 777 patients were operated upon pancreatic and periampullary carcinomas. The vast majority of patients were operated upon pancreatic ductal adenocarcinoma (n = 566, 73%), followed by carcinomas of the papilla of Vater (n = 112, 14%), pancreatic neuroendocrine carcinomas (n = 39, 5%), intraductal papillary mucinous neoplasms (n = 33, 4%), and distal bile duct carcinomas (n = 27, 3%). Fresh-frozen tissue sections from 169 lymph nodes (LNs) classified as tumor free by routine histopathology from 57 patients with R0 resected carcinoma of the papilla of Vater who had been spared from adjuvant chemotherapy were immunohistochemically (IHC) examined, using a sensitive IHC assay with the anti-epithelial monoclonal antibody Ber-EP4 for tumor cell detection. With regard to histopathology, 39 (63%) of the patients were staged as pT1/pT2, 21 (37%) as pT3/pT4, 30 (53%) as pN0, while 38 (67%) as G1/G2. RESULTS: Of the 169 "tumor-free" LNs, 91 LNs (53.8%) contained Ber-EP4-positive tumor cells. These 91 LNs were from 40 (70%) patients. The mean overall survival in patients without nodal microinvolvement of 35.8 months (median-not yet reached) was significantly longer than that in patients with nodal microinvolvement (mean 16.6; median 13; p = 0.019). Multivariate Cox regression analysis for overall survival revealed that grading was the most significant independent prognostic factor (p = 0.001), followed by nodal microinvolvement (p = 0.013). CONCLUSIONS: The influence of occult tumor cell dissemination in LNs of patients with histologically proven carcinoma of the papilla of Vater supports the need for further tumor staging through immunohistochemistry.


Subject(s)
Adenocarcinoma/secondary , Adenocarcinoma/surgery , Ampulla of Vater/pathology , Common Bile Duct Neoplasms/pathology , Common Bile Duct Neoplasms/surgery , Lymph Nodes/pathology , Adenocarcinoma/drug therapy , Adenocarcinoma/mortality , Adult , Aged , Aged, 80 and over , Biopsy, Needle , Chemotherapy, Adjuvant , Cohort Studies , Common Bile Duct Neoplasms/drug therapy , Common Bile Duct Neoplasms/mortality , Female , Humans , Immunohistochemistry , Kaplan-Meier Estimate , Lymph Node Excision , Lymphatic Metastasis , Male , Middle Aged , Multivariate Analysis , Neoplasm Staging , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/mortality , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/surgery , Probability , Prognosis , Proportional Hazards Models , Retrospective Studies , Risk Assessment , Statistics, Nonparametric , Survival Analysis , Treatment Outcome
20.
Cancer Cell ; 13(5): 441-53, 2008 May.
Article in English | MEDLINE | ID: mdl-18455127

ABSTRACT

The increasing use of primary tumors as surrogate markers for prognosis and therapeutic decisions neglects evolutionary aspects of cancer progression. To address this problem, we studied the precursor cells of metastases directly for the identification of prognostic and therapeutic markers and prospectively analyzed single disseminated cancer cells from lymph nodes and bone marrow of 107 consecutive esophageal cancer patients. Whole-genome screening revealed that primary tumors and lymphatically and hematogenously disseminated cancer cells diverged for most genetic aberrations. However, we identified chromosome 17q12-21, the region comprising HER2, as the most frequent gain in disseminated tumor cells that were isolated from both ectopic sites. Survival analysis demonstrated that HER2 gain in a single disseminated tumor cell but not in primary tumors conferred high risk for early death.


Subject(s)
Chromosomes, Human, Pair 17 , Esophageal Neoplasms/genetics , Esophageal Neoplasms/pathology , Genome, Human , Bone Neoplasms/pathology , Bone Neoplasms/secondary , Chromosome Mapping , Esophageal Neoplasms/therapy , Genes, erbB-2 , Humans , Lymphatic Metastasis , Neoplasm Metastasis , Neoplasm Staging , Predictive Value of Tests , Prognosis , Treatment Outcome
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