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  • 1
    Keywords: CELLS ; EXPRESSION ; GROWTH ; INVASION ; tumour ; mechanisms ; BREAST-CANCER ; IDENTIFICATION ; METASTASIS ; COLORECTAL-CANCER ; REGULATORS ; DISSEMINATION ; TISSUE INHIBITOR ; MOTILITY ; CELL MOTILITY ; DOWNSTREAM
    Abstract: We have previously reported that over-expression of a panel of 119 genes correlates with the metastatic potential of pancreatic carcinoma cells. We sought to identify and functionally characterize candidate tumour metastasis promoting genes among this library using a secondary phenotype-assisted screen. Here we report the discovery of the metastasis-promoting function of a hitherto not characterized gene located on chromosome 14 (ORF138), which we have named 'novel metastasis-promoting gene 1' (NVM-1). The NVM-1 transcript is extensively alternatively spliced, is expressed endogenously in a number of different tissues, and is strongly over-expressed at the protein level in a variety of human tumour types. Importantly, NVM-1 expression stimulates the migratory and invasive behaviour of tumour cells and promotes metastasis formation in experimental animals in vivo. Up-regulation of FMNL2 and MT1E and down-regulation of TIMP4 and MHC-I is observed as a consequence of NVM-1 expression. Together these data identify NVM-1 as a gene that is functionally involved in tumour metastasis, and suggest that NVM-1 may constitute a promising therapeutic target for inhibition of tumour metastasis.
    Type of Publication: Journal article published
    PubMed ID: 21744341
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  • 2
    Keywords: SPECTRA ; CANCER ; CELLS ; carcinoma ; Germany ; SYSTEM ; SYSTEMS ; PROTEIN ; PROTEINS ; MONOCLONAL-ANTIBODY ; PATIENT ; ANTIGEN ; CONTRAST ; T-CELL ; FREQUENCY ; H-1 ; MAGNETIC-RESONANCE ; MOLECULE ; antibodies ; antibody ; Drosophila ; COLORECTAL-CANCER ; ADHESION ; EPITHELIAL-CELLS ; CARCINOEMBRYONIC ANTIGEN ; CARCINOMAS ; BOVINE SERUM-ALBUMIN ; IMMUNOTHERAPY ; ADHESION MOLECULE ; CANCER PATIENTS ; HEALTHY ; RANDOMIZED-TRIAL ; AUTOANTIBODIES ; SERUM ; RECOMBINANT ; EP-CAM ; CARCINOMA PATIENTS ; cell adhesion ; recombinant protein ; ANTIIDIOTYPIC ANTIBODY ; COMPLEMENT ACTIVATION
    Abstract: The human epithelial cell adhesion molecule (EpCAM) is expressed on normal epithelial cells and is overexpressed in most carcinomas. EpCAM-targeted immunotherapy has been tried in several clinical studies. High titers of autoantibodies against EpCAM have been reported by different authors. We have generated large amounts of purified protein in S2 Drosophila cells (S2-EpCAM) with a purity of 〉96%. In contrast, the protein produced in baculovirus-dependent systems (baculo-EpCAM) that has been used in previous. studies shows a purity of 79%. H-1 nuclear magnetic resonance spectrum of S2-EpCAM is typical of folded protein, whereas the baculo-EpCAM sample shows a spectrum corresponding to a partially unfolded. protein. Using S2-EpCAM, denatured S2-EpCAM, and baculo-EpCAM, we measured EpCAM Abs of different isotypes in the serum of healthy controls and cancer patients. We found Ab titers against EpCAM in a much lower percentage of sera as published previously, and support the hypothesis that Ab reactivity in some published studies might be due to reactivity against denatured protein, to contaminating proteins in the baculovirus preparations, and to reactivity with BSA. Tetanus toxoid-reactive IgG Abs are present in 1000-fold higher titers compared with EpCAM-reactive Abs. Only IgA Abs were found in higher proportions and in higher concentrations than tetanus toxoid-specific Abs. Our study shows that EpCAM only rarely induces autoantibodies against native protein and emphasizes the importance of using extremely purified Ag preparations when evaluating Abs against tumor-associated Ags
    Type of Publication: Journal article published
    PubMed ID: 15634917
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  • 3
    Keywords: HEPATOCELLULAR-CARCINOMA ; LIVER-TRANSPLANTATION ; RESECTION ; OVEREXPRESSION ; SINGLE-CENTER EXPERIENCE ; intrahepatic cholangiocarcinoma ; HILAR CHOLANGIOCARCINOMA ; NEOADJUVANT CHEMORADIATION ; MET EXPRESSION ; MACC1
    Abstract: Curative treatment of intrahepatic cholangiocarcinoma (ICC) and hilar cholangiocarcinoma (Klatskin tumors) is limited to surgical resection or orthotopic liver transplantation. However, not all patients benefit from a surgical approach and suffer from early tumor recurrence. Response to chemotherapy is generally poor and, until today, no targeted therapy could be established. Metastasis-associated in colon cancer 1 (MACC1) is a recently discovered regulator of the hepatocyte growth factor (HGF)/Met/mitogen-activated protein kinase pathway, which induces proliferation, migration, and invasion in cell culture, as well as metastasis in mice. MACC1 expression shows a significant correlation with Met expression in colon cancer tissue and is highly prognostic for occurrence of distant metastasis and survival in colon cancer patients. Thus, we aimed to measure the expression of MACC1, Met, and HGF messenger RNA in microdissected tumor tissue and corresponding normal liver tissue of 156 patients with Klatskin tumors (n = 76) and ICC (n = 80) using real-time quantitative reverse-transcriptase polymerase chain reaction. We used immunohistochemical staining to validate the results. MACC1 expression in tumor tissue of both tumor entities was significantly higher than in corresponding normal liver tissue (P 〈 0.001). Klatskin tumor patients with a history of tumor recurrence had significantly higher MACC1 expression than those without tumor recurrence (P = 0.005). Uni- und multivariate survival analysis showed that Klatskin tumor patients with high MACC1 had a significantly shorter overall (OS) and disease-free survival (DFS; P = 0.001 and P 〈 0.001, respectively). The multivariate analysis confirmed MACC1 to be an independent factor for overall survival in Klatskin tumor patients (hazard ratio: 2.777; 95% confidence interval: 1.389-5.555; P = 0.004). CONCLUSION: Our study identified MACC1 as a highly prognostic biomarker for OS and DFS in Klatskin tumor patients. MACC1 expression could become an important diagnostic tool and might be a candidate for targeted therapy. (Hepatology 2015).
    Type of Publication: Journal article published
    PubMed ID: 25953673
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  • 4
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    German Medical Science; Düsseldorf, Köln
    In:  68. Jahrestagung der Deutschen Gesellschaft für Unfallchirurgie, 90. Tagung der Deutschen Gesellschaft für Orthopädie und Orthopädische Chirurgie und 45. Tagung des Berufsverbandes der Fachärzte für Orthopädie; 20041019-20041023; Berlin; DOC04dguO10-1711 /20041019/
    Publication Date: 2004-10-20
    Keywords: ddc: 610
    Language: German
    Type: conferenceObject
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  • 5
    Keywords: RECEPTOR ; CANCER ; EXPRESSION ; carcinoma ; SYSTEM ; PROTEIN ; PATIENT ; COMPLEX ; DOMAIN ; ANTIGEN ; BREAST-CANCER ; antibodies ; antibody ; FORM ; PLASMA ; COLORECTAL-CANCER ; adenocarcinoma ; tumor marker ; AUTOANTIBODIES ; SERUM ; ELISA ; colon cancer ; OSTEOPONTIN ; EpCAM ; LYMPHOCYTE ; Enzyme linked immunosorbent assay ; Humoral tolerance
    Abstract: The measurement of tumor-associated proteins is of high diagnostic value in the follow-up of cancer patients. Most tests ignore that various forms of the protein can exist; especially in epithelial cancers and the soluble receptors they produce. We choose EpCAM as model-antigen to analyze whether tests recognizing different domains of the protein give different results in patients' sera. EpCAM-reactive autoantibodies are present in the sera of patients with colorectal carcinoma, however little is known about the existence and possible relevance of circulating soluble EpCAM protein. Most monoclonal EpCAM-antibodies recognize the first EGF-like repeat and fail to detect N-terminal trimmed protein. We developed a novel ELISA to determine the concentration of serum EpCAM with mAbs recognizing the second EGF-like repeat. In 59 healthy controls, EpCAM concentrations ranged from 232 to 8893 ng/ml (mean 1525 ng/ml). Levels of EpCAM in 412 patients with adenocarcinoma were somewhat higher with concentrations ranging from 176 to 36,259 ng/ml (mean 1971 ng/ml). In direct comparison, the untrimmed protein specific ELISA detected lower levels and frequencies as compared to the EGFII-specific ELISA. Only sera with less than 1 mu g/m1 circulating EGFII-EpCAM (66% of the sera) contained EpCAM-specific IgG antibodies. The absence of IgG antibodies in the sera with more than 1 mu g/ml circulating EpCAM was not due to immune complex formation. Anti-EpCAM IgA and IgM antibodies did not show such a correlation. It will be important to assess whether the presence of high levels of circulating EGFII-EpCAM is associated with side effects in patients given immunotherapy.
    Type of Publication: Journal article published
    PubMed ID: 22387297
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  • 6
    ISSN: 0309-1651
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-2323
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé Contrastant de plus en plus avec le traitement standardisé des cancers primitifs gastro-intestinaux, la thérapeutique des récidives loco-régionales n'est pas uniforme. Dans la majorité des cas le traitement des récidives ne peut être assuré par la seule chirurgie. Il est nécessaire d'avoir recours à des méthodes complémentaires. La récidive des cancers colo-rectaux dépend de facteurs propres au processus tumoral qui contre-carrent l'action de la chirurgie. Chez près de 50% des malades qui présentent une récidive locale, il est constaté une généralisation de la tumeur lors du diagnostic. Plus de 75% des malades accusant des troubles, ce fait vient discréditer les examens post-opératoires. Le pourcentage des malades opérés pour récidive locale a légèrement augmenté au cours des 25 dernières années. Il atteint 26.4% dans la série des auteurs. Le temps médian de survie est de 19 mois chez des malades qui subissent une intervention dite radicale, de 13 mois lorsque l'intervention n'est pas radicale, de 6–8 mois quand l'intervention est palliative. L'état des ganglions, allant de paire avec la tumeur primitive, représente un facteur décisif: 27% des malades N0 peuvent subir une nouvelle résection, celle-ci n'étant possible que dans 13% des cas pour les malades N1. Dans le cas du cancer gastrique les chances de guérison des récidives loco-régionales sont minimes du fait que l'exérèse des ganglions lymphatiques lors de l'intervention initiale se solde souvent par une carcinose péritonéale généralisée. Seules les récidives au niveau du moignon gastrique peuvent subir une résection secondaire susceptible d'être radicale. Le taux des malades opérés pour une récidive de cancer gastrique est inférieur à 10%. En outre, comme l'intervention exploratrice est grevée d'une lourdre mortalité, les cancers inopérables devraient être dépistés grâce aux nouvelles méthodes d'investigations. En raison de ces résultats décourageants, il semble indispensable d'avoir recours à des essais contrôlés de modalités thérapeutiques complémentaires: chimiothérapie et radiothérapie pré-, per-, et post-opératoires, ces moyens adjuvants étant susceptibles de réduire le taux des récidives.
    Abstract: Resumen En contraste con las formas cada vez más estandarizadas de tratamiento de los cánceres gastrointestinales primarios, la estrategia terapéutica frente a las recurrencias locorregionales requiere enfoques altamente individualizados. En la mayoría de los pacientes no es posible la curación, y si ésta se logra es sólo mediante la combinación de cirugía y otras modalidades terapéuticas adyuvantes. En las recurrencias del cáncer colorrectal diversos factores relativos a la biología tumoral limitan los alcances quirúrgicos. Alrededor del 50% de los pacientes presentan extensión tumoral generalizada en el momento en que se hace el diagnóstico de una recurrencia local, y más del 75% presentan síntomas contra sólo 25% en quienes un seguimiento meticuloso permite la detección de la recurrencia locorregional en el estado asintomático. El porcentaje de pacientes operados para curación ha aumentado apenas ligeramente en el curso de los últimos 25 años; en nuestra serie la tasa es de 26.4%. Estos pacientes son los que más se benefician y exhiben una supervivencia media de 19 meses, comparada con 13 meses para aquellos sometidos a procedimientos no radicales, y 6–8 meses para los sometidos a intervenciones paliativas. El estado de los ganglios del tumor primario es un factor decisivo: 27% de los pacientes en estado N0 pudieron ser resecados en contraste con sólo 13% del estado N1. En el cáncer gástrico la posibilidad de curación en recurrencias locorregionales es mínima porque la remoción de los ganglios de drenaje linfático con la operación primaria da lugar a carcinomatosis peritoneal generalizada en casi todos los casos. Solamente en el caso de recurrencia en el muñón gástrico una resección secundaria puede ser de carácter radical. La tasa de resección en pacientes con recurrencia de cáncer gástrico es de menos de 10%. Teniendo en cuenta que aún una laparotomía resulta en elevada mortalidad operatoria, las situaciones inoperables deben ser identificadas preoperatoriamente mediante procedimientos de imagenología. Puesto que no existen enfoques promisorios en el manejo de las recurrencias, deben estudiarse los ensayos clínicos con terapias adyuvantes, tales como quimio y radioterapia, intra y postoperatoria, con ocasión de la resección del tumor primario con el propósito de rebajar la tasa de recurrencias.
    Notes: Abstract In contrast to the more standardized treatment of primary gastrointestinal cancers, the therapeutic concept in locoregional recurrences requires very individualized approaches. In most patients cure cannot be obtained and those patients who are cured are cured only by combining surgery with adjunctive treatment modalities. In recurrences of colorectal cancer, tumor biological factors limit surgical efforts. In about 50% of the patients, generalized tumor spread is present at the time of diagnosis of a local relapse. More than 75% of the patients present with symptoms thus calling into question the effect of routine follow-up examinations. The percentage of patients operated on for cure has only slightly increased during the past 25 years. In our series the rate is 26.4%. These patients benefit most, showing a median survival time of 19 months compared to 13 months in nonradical procedures and 6–8 months in palliative interventions. Nodal status of the primary tumor is very important: 27% of the patients with N0 could be re-resected compared to only 13% with N1 histological findings. In gastric cancer, the chance for cure in locoregional recurrences is minimal since the removal of the draining lymph nodes at the primary operation leads to generalized peritoneal carcinomatosis in almost all patients. Only in recurrences in the gastric stump should secondary resection be radical. Less than 10% of patients undergo resection for gastric cancer recurrence. Since even explorative laparotomy yields a high operative mortality, inoperable situations should be identified preoperatively by imaging procedures. Since encouraging approaches in the treatment of recurrences are lacking, adjuvant pre-, intra-, and postoperative chemo- and radiotherapy at the time of resection of the primary tumor should be evaluated in controlled trials.
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Der Chirurg 69 (1998), S. 1315-1322 
    ISSN: 1433-0385
    Keywords: Key words: Metastatic cascade ; Adhesion ; Proteolysis ; Growth factors ; Angiogenesis ; Therapy. ; Schlüsselwörter: Metastatische Kaskade ; Adhäsion ; Proteolyse ; Wachstumsfaktoren ; Angiogenese ; Therapie.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung. Die Entstehung von Metastasen setzt eine Vielzahl von Einzelschritten voraus, die Tumorzellen bewältigen müssen, bevor sie vom Primärtumor entfernt andernorts manifest werden. Als einer der ersten Schritte wird die epitheliale Integrität durch Zelladhäsionsverlust aufgehoben. Die Proteolyse der extracellulären Matrix sowie eine gesteigerte Lokomotion der malignen Zellen führt letztendlich zur Intravasation und Dissemination. Tumorzellen müssen dann wieder an das Endothel adhärieren und im Metastasierungsorgan das Gefäßsystem verlassen. Die Etablierung dort bedarf neben proteolytischer und adhäsiver Prozesse insbesondere der Neoangiogenese, die das Metastasenwachstum initiiert und aufrechterhält. Aus diesem Grund erscheint insbesondere eine antiangiogene sowie antiproteolytische Therapie ein sinnvoller neuer Therapieansatz, das Metastasenwachstum zu unterbinden. Ob dieses Ziel durch synthetische oder endogene Substanzen erreichbar ist, wird die weitere Grundlagen- und letztendlich klinische Forschung zeigen müssen.
    Notes: Summary. Metastasis formation is a multistep process that requires tumor cells to progress through many different stages. One of the first steps is a disturbance of the epithelial integrity through a decrease in intercellular homotypic adhesion. Proteolysis of the extracellular matrix, as well as increased locomotion, leads to intravasation and dissemination of the tumor cells. In the target organs metastasizing cells adhere to the endothelium, extravasate and form metastases. Finally, neoangiogenesis is required for the initiation as well as the growth of the metastases, providing the tumor cells with both nutritive agents and growth factors. This leads to the conclusion that anti-proteolytic and anti-angiogenic substances could provide effective therapeutic approaches for the control of metastatic growth. Whether or not this goal can be accomplished by synthetic or endogenous drugs must still be demonstrated by basic and definitive clinical research.
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  • 9
    ISSN: 1433-0385
    Keywords: Key words: Breast cancer ; Sentinel node ; Axillary dissection ; Lymphoscintigraphy ; Morbidity. ; Schlüsselwörter: Mammacarcinom ; „Sentinel node“ ; Axilladissektion ; Lymphabstromszintigraphie ; Morbidität.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung. Die Detektion des ersten tumordrainierenden Lymphknotens beim Mammacarcinom kann durch Anwendung von Farbstofflösungen (Patentblau) oder durch 99mTc markierte Kolloide in Kombination mit einer präoperativen Lymphabstromszintigraphie erfolgen. Ein „sentinel node“ (SN) kann bei 80 bis 85 % der Patienten detektiert werden, wobei eine Abhängigkeit von der Tumorgröße besteht. Durch die szintigraphische Verfolgung des Lymphabflußgebietes werden tumordrainierende Lymphknoten auch im Bereich der A. mammaria interna nachgewiesen. Die diagnostische Übereinstimmung zwischen dem histologischen Befund des SN und der durch Axilladissektion gewonnenen Lymphknoten beträgt etwa 95 %. Aufgrund der unterschiedlichen diagnostischen Prozeduren unter Verwendung verschiedener Radiopharmaka ist es erforderlich, daß jedes Zentrum seine eigene Lernphase absolviert. Sicherheit, durch die SN-Detektion eine der Axilladissektion gleichwertige Aussage über den Lymphknotenstatus zu gewinnen, kann frühestens nach etwa 100 Patientinnen mit SN-Detektion und anschließender Axillaausräumung sowie Übereinstimmung des histologischen Status bei mindestens 95 % gegeben sein. Für die histopathologische Aufarbeitung der Lymphknoten beim Mammacarcinom eröffnet die SN-Detektion die Möglichkeit, gezielt mit immunhistochemischen Methoden eine Metastasierung nachzuweisen. Eine Senkung der globalen Morbidität des Mammacarcinoms kann dadurch erreicht werden, daß nur noch diejenigen Patientinnen der Axilladissektion unterzogen werden, bei denen eine lymphogene Metastasierung auch tatsächlich vorliegt. Indikationskriterien hierzu sind Tumoren unter 2 cm (T1) mit klinisch unauffälligem axillärem Status sowie Patientinnen mit einem duktalen Carcinoma in situ (DCIS), bei denen durch die Excision des SN eine höhere Sicherheit erzielt werden kann, daß kein invasives, metastasierendes Carcinom vorliegt.
    Notes: Summary. The aim of sentinel node biopsy (SN) in breast cancer patients is to detect the tumor-draining lymph node by means of isosulfan blue or 99mTc-labelled colloids. SN can be detected in 80 to 85 % of the patients, depending on the size of the tumor. Preoperative lymphoscintigraphy permits the draining nodes along the internal mammary artery also to be visualized. The predictive value of the histological findings of SN for lymph nodes obtained from axillary dissection is about 95 %. Because of different diagnostic procedures using various radiotracers each center has to follow its own learning curve. To be sure that the nodal status derived from a SN procedure is of identical value to axillary dissection about 100 patients have to undergo sentinel node detection, followed by axillary dissection, and concordant results should be obtained in 95 % of them at least. The SN, however, offers a chance of assessing the lymph node at risk for metastasis by more detailed histological procedures. Morbidity as a result of treatment for primary breast cancer can be decreased if only patients suffering from metastatic disease are subjected to axillary dissection. Currently, the indication criteria for a SN procedure should be restricted to small tumors (T1) with clinically uninvolved axillary status and patients with ductal carcinoma in situ (DCIS).
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Der Chirurg 70 (1999), S. 123-132 
    ISSN: 1433-0385
    Keywords: Key words: Liver metastases ; Staging ; Curative resection ; Prognosis. ; Schlüsselwörter: Lebermetastasen ; Staging ; kurative Resektion ; Prognose.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung. Für Patienten mit Lebermetastasen stellt heute die chirurgische Therapie mit 5-Jahres-Überlebensraten von 25–35 % die einzige Chance auf eine Kuration dar. Verbesserungen von chirurgischen und anaesthesiologischen Techniken sowie Fortschritte auf dem Gebiet der Intensivtherapie haben zu einer deutlichen Senkung der Morbidität ( 〈 25 %) und Letalität ( 〈 5 %) geführt. Ein Langzeit-rezidivfreies Überleben kann bei 20–25 % der Patienten erzielt werden. Ein potentiell kurativer chirurgischer Eingriff ist jedoch bei nur 10–15 % der Patienten mit Lebermetastasen möglich. Es ist somit von großer Bedeutung diejenigen Patienten, die von einer Operation profitieren könnten, durch ein sorgfältiges Staging zu selektionieren. Bei colorectalen Lebermetastasen ist eine potentielle Kuration nur durch eine radikale Resektion möglich. Bei einem Großteil der Patienten mit symptomatischen Lebermetastasen neuroendokriner Tumoren kann durch Resektion im Sinne einer Tumormassenreduktion eine Langzeitpalliation erzielt werden. Von den potentiell kurativ resezierten Patienten können nur einige von ihnen geheilt werden. Die Indikationsstellung zur Resektion nicht colorectaler und nicht neuroendokriner Lebermetastasen ist aufgrund kleiner Fallzahlen und geringer Erfahrungen weniger klar definiert. Ein Rezidiv von Lebermetastasen nach einem potentiell kurativen Eingriff tritt bei mehr als 40–60 % der Patienten auf. Eine Resektion des Rezidivs ist bei nur 20–35 % dieser Patienten möglich. Hierbei beträgt die 3-Jahres-Überlebensrate um 30 %. Die Morbidität und Letalität nach Reresektion sind mit denen der ersten Leberresektion vergleichbar. Alle Ergebnisse zusammengenommen zeigen, daß die Resektion und Reresektion von Lebermetastasen bei sorgfältig selektionierten Patienten ohne extrahepatische Tumormanifestation mit einem Langzeitüberleben verbunden ist.
    Notes: Summary. For patients with liver metastases, surgery currently represents the only possibility for cure, with a mean 5-year survival rate of 25–35 %. Due to refinement in operative and anesthetic techniques and improved critical care with decreased morbidity ( 〈 25 %) and mortality ( 〈 5 %), hepatic resection is a safe and efficient procedure. Surgery has repeatedly achieved long-term disease-free survival in 20–25 % of patients. However, only 10–25 % of patients with colorectal liver metastases can undergo potentially curative liver resection. Therefore, accurate staging plays a pivotal role in selecting patients who would benefit from surgery. For metastatic colorectal cancer, resection offers the only potential for cure. For symptomatic neuroendocrine tumors, hepatic resection offers long-term palliation in many cases and cure in some. The role of hepatic resection for noncolorectal and nonneuroendocrine metastases, however, is less well defined. Recurrence of hepatic metastases after seemingly curative resection is observed in about 40–60 % of the cases. Only 20–35 % of these recurrent metastases appear to be resectable, resulting in an overall 3-year survival rate of about 30 %. The morbidity and mortality from repeat hepatectomy is similar to that of first hepatic resection. All results together demonstrate that resection and re-resection of liver metastases can provide long-term survival rates and can be beneficial in a carefully selected group of patients without extrahepatic disease.
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