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Metastatic Spread (metastatic + spread)
Selected AbstractsSmall bowel tumours: a 10 year experience in four sydney teaching hospitalsANZ JOURNAL OF SURGERY, Issue 9 2004David S. Rangiah Background: Small bowel tumours are uncommon and can have a long delay prior to diagnosis. The present study aims to compare the use of computed tomography (CT) and contrast small bowel series (SBS) in their diagnosis and to outline the clinical features of small bowel tumours. Methods: A retrospective, case note study was conducted between 1990 and 2000 in four Sydney teaching hospitals. The data collected included clinical features, investigations and tumour characteristics. Results: One hundred and sixty-six people with small bowel tumours were identified (91 malignant; 75 benign). Malignant tumours consisted of adenocarcinomas (31%), carcinoid tumours (12%), lymphomas (7%) and leiomyosarcomas (5%). Benign tumours consisted of adenomas (22%), hamartomas (13%), leiomyomas (4%), inflammatory polyps (4%) and hyperplastic polyps (2%) and a benign schwannoma (1%). Adenocarcinomas were mainly located in the duodenum (P < 0.001) and carcinoid tumours in the ileum (P < 0.001). Malignant tumours were associated with a higher proportion of symptoms (P < 0.01), signs (P < 0.001) and episodes of small bowel obstruction (P < 0.01). Abdominal CT scans demonstrated a greater sensitivity (87.7%) than SBS (72.9%) with a slightly improved sensitivity when both investigations were used (89.3%). Abdominal ultrasound had a lower sensitivity than both of the above investigations of 65%. Gastroduodenoscopy had a sensitivity of 90% for diagnosing duodenal tumours. Operative procedures were performed on 92 patients with a preoperative diagnosis made in 77%. Metastatic spread of malignant tumours was evident in 46%. The sites of spread were to lymph nodes (23%), liver (21%) and distant locations (2%) at diagnosis. Conclusions: Malignant small bowel tumours are more likely to produce symptoms and signs than benign tumours, particularly caused by small bowel obstruction. Abdominal CT is the best radiological investigation for small bowel tumours and has a slight complimentary effect with SBS in improving the chances of detection. Gastroduodenoscopy remains the best investigation of duodenal tumours. [source] Renal Adenocarcinoma with Intramyopericardial and Right Atrial Metastasis, Latter via Coronary Sinus: Report of a CaseECHOCARDIOGRAPHY, Issue 4 2005Morteza Rohani M.D. Primary renal tumors with intracardiac metastasis are not infrequent. Most of the secondary spread is blood-borne and occurs via inferior vena cava. Patients with such a spread often present with cardiac symptoms. We presume that a metastatic spread in the right atrium through coronary sinus has never been reported in the literature according to the result of a Medline search at the time of writing this report. [source] How does the periapical inflammatory process compromise general health?ENDODONTIC TOPICS, Issue 1 2004Idikó. Several lines of evidence support the causative role of oral inflammatory lesions and certain systemic diseases, such as atherosclerosis and cardiovascular diseases, adverse pregnancy outcome and lung diseases. Properly executed epidemiologic studies identified increased odds ratios. Local or metastatic spread of oral microorganisms, local production of microbial or host-derived soluble regulatory molecules, that may initiate or sustain inflammatory events in remote tissues and organs and the presence of (a) common , extrinsic- or intrinsic-pathological mechanism(s) may result in or contribute to both local and systemic inflammation. A number of cross-sectional studies addressing a possible association between oral health and systemic diseases have also investigated the presence or the absence of periapical lesions. However, these studies cannot either confirm or refute a role of the periapical inflammatory lesion in the observed associations, since other variables of oral health might have exerted an inestimable influence on general health of the assessed population. The literature, dealing with patients with root canal infections and apical periodontitis as sole oral inflammatory lesions is extremely sparse. Our group has demonstrated that young adults with apical periodontitis exhibit certain biochemical changes, such as elevated levels of C-reactive protein and an increased whole blood chemiluminescence, which have been shown to elevate the risk for cardiovascular diseases. Future research will be required to determine whether and to what extent may endodontic diseases affect general health. [source] New pharmacological strategies against metastatic spreadFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 5 2008G.Y. Perret Abstract Although metastatic spread is the most frequent cause of death in cancer patients, there are very few drugs specifically targeting this process. Bases for a new antimetastatic drug discovery strategy are weak because a great number of unknowns characterize the complete understanding of the metastatic cascade mechanisms. Moreover, the current experimental models are too simplistic and do not account for the complexity of the phenomenon. Some targets have been identified but too few are validated. Among them, the metastasis suppressor genes seem to be the most promising. In spite of this, during recent years, a dozen of molecules, which fulfil the definition of a specific metastatic drug that inhibits the metastases without altering the growth of the primary tumour (which can be eradicated by surgery), have been identified and assessed for the proof of the concept. The continuation of this effort would benefit in terms of efficiency, if the objectives were defined more precisely. It is particularly important to distinguish molecules that prevent spread of the metastatic cells of the early-stage primary tumour from the ones which induce a regression of the established metastases or to inhibit the transition from disseminated occult tumour cells to dormant micrometastasis. This second goal is a priori more relevant in the current clinical setting where the detection of early metastatic spread is very difficult, and therefore would call for greater effort on the part of the scientific community. [source] Relevance of translocation type in myxoid liposarcoma and identification of a novel EWSR1-DDIT3 fusionGENES, CHROMOSOMES AND CANCER, Issue 11 2007B. Bode-Lesniewska The clinical course of myxoid/round cell liposarcoma (MRCL) is characterized by frequent local recurrences and metastases at unusual sites. MRCLs carry specific translocations, t(12;16) or rarely t(12;22), linking the FUS or the EWSR1 gene with the DDIT3 gene, respectively. Nine FUS/DDIT3 and three EWSR1/DDIT3 variants of fusion transcripts have been described thus far. In search of prognostic markers for MRCL, we analyzed the translocation types of 31 patients and related them to the event free and overall survival. Using break-apart FISH and RT-PCR combined with DNA sequencing, we detected FUS/DDIT3 fusions in 30 sarcomas, while an EWSR1/DDIT3 translocation was identified in one tumor. FUS/DDIT3 type II (exons 5-2) was most commonly detected (20 cases), followed by type I (7-2) (7 cases) and type III (8-2) (3 cases). A single tumor carrying a t(12;22) translocation expressed a hitherto unknown EWSR1-DDIT3 fusion transcript (13-3) linking the complete RNA-binding domain of EWSR1 with a short piece of the 5,-UTR and the entire open reading frame of the DDIT3 gene. Interestingly, five of six patients with type I (7-2) FUS/DDIT3 fusions displayed local recurrences and/or metastatic spread within the first 3 years, generally requiring chemotherapeutical treatment (median disease-free survival 17 months). In contrast, 9 of 13 patients with type II FUS/DDIT3 translocations remained at 3 years disease-free (median disease-free survival 75 months). Since the total number of patients is still limited, further studies are required to verify a putative association of type I FUS/DDIT3 -fusion transcripts with a prognosis of MRCL. © 2007 Wiley-Liss, Inc. [source] Head and neck mucosal melanoma: Experience with 42 patients, with emphasis on the role of postoperative radiotherapyHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 12 2008Marco Meleti DDS Abstract Background. Treatment of head and neck mucosal melanoma remains a challenge. Surgery has traditionally been the main therapeutic approach. The role of postoperative radiotherapy has never been clearly established. Methods. The experience with a group of 42 patients (16 males, 26 females) with a primary head and neck mucosal melanoma is reported. Results. Eleven of 19 patients (57.9%) receiving surgery alone developed a regional lymphatic metastasis. For patients receiving postoperative radiotherapy (19 patients), regional metastatic spread occurred in 4 patients (21%). Percentages of local failure were 57.9% (11/19) and 26.3% (5/19) for patients treated with surgery alone and for those treated with surgery and radiotherapy, respectively. Distant metastases occurred in 10 of 19 patients (52.6%) receiving surgery alone and in 9 of 19 patients (47.3%) receiving both therapies. Conclusions. The present evaluation confirms a poor prognosis for patients with head and neck mucosal melanoma, independent of the treatment modality. © 2008 Wiley Periodicals, Inc. Head Neck, 2008 [source] Calcifying epithelial odontogenic (Pindborg) tumor with malignant transformation and metastatic spreadHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 8 2001Michael J. Veness MB Abstract Background Pindborg tumors (calcifying epithelial odontogenic tumors) are uncommon neoplasms of odontogenic origin most often located in the posterior mandible. First described in detail in 1955 by Pindborg, these tumors are considered benign but can be locally aggressive in nature, with recurrence rates of 10% to 15% reported. The malignant form of this tumor is exceedingly rare. Methods We describe the case of a 64-year-old woman initially treated for a painful infected left mandibular third molar. The patient underwent extraction of the tooth and excision of an associated soft tissue component. Subsequent histologic review identified a Pindborg tumor of the left posterior mandible. Results After initial excision, this tumor recurred twice, with the recurrences exhibiting a progression to a malignant Pindborg tumor (odontogenic carcinoma) with vascular invasion and spread to a cervical lymph node. Further treatment involved radical surgery and adjuvant radiotherapy. At last review 12 months after treatment, the patient was disease free. Conclusions This article describes only the second case of odontogenic carcinoma. The transformation from benign to malignant histologic findings has not previously been documented in this tumor. The salient clinical features of this case are presented along with supportive pathologic and radiologic evidence. © 2001 John Wiley & Sons, Inc. Head Neck 23: 692,696, 2001. [source] Gene signatures of pulmonary metastases of renal cell carcinoma reflect the disease-free interval and the number of metastases per patientINTERNATIONAL JOURNAL OF CANCER, Issue 2 2009Daniela Wuttig Abstract Our understanding of metastatic spread is limited and molecular mechanisms causing particular characteristics of metastasis are largely unknown. Herein, transcriptome-wide expression profiles of a unique cohort of 20 laser-resected pulmonary metastases (Mets) of 18 patients with clear-cell renal cell carcinoma (RCC) were analyzed to identify expression patterns associated with two important prognostic factors in RCC: the disease-free interval (DFI) after nephrectomy and the number of Mets per patient. Differentially expressed genes were identified by comparing early (DFI , 9 months) and late (DFI , 5 years) Mets, and Mets derived from patients with few (,8) and multiple (,16) Mets. Early and late Mets could be separated by the expression of genes involved in metastasis-associated processes, such as angiogenesis, cell migration and adhesion (e.g., PECAM1, KDR). Samples from patients with multiple Mets showed an elevated expression of genes associated with cell division and cell cycle (e.g., PBK, BIRC5, PTTG1) which indicates that a high number of Mets might result from an increased growth potential. Minimal sets of genes for the prediction of the DFI and the number of Mets per patient were identified. Microarray results were confirmed by quantitative PCR by including nine further pulmonary Mets of RCC. In summary, we showed that subgroups of Mets are distinguishable based on their expression profiles, which reflect the DFI and the number of Mets of a patient. To what extent the identified molecular factors contribute to the development of these characteristics of metastatic spread needs to be analyzed in further studies. © 2009 UICC [source] Vascular endothelial growth factor (VEGF), VEGF receptors expression and microvascular density in benign and malignant thyroid diseasesINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 4 2007Ala'eddin Jebreel Summary Angiogenesis is critical for the growth and metastatic spread of tumours. Vascular endothelial growth factor (VEGF) is the most potent inducer of neovasculature, and its increased expression has been related to a worse clinical outcome in many diseases. The purpose of this study was to evaluate the relation between VEGF, its receptors (VEGFR-1 and VEGFR-2) and microvessel density (MVD) in thyroid diseases. Immunostaining for VEGF and VEGF receptors was performed in 66 specimens of thyroid tissue, comprising 17 multinodular goitre (MNG), 14 Graves' disease, 10 follicular adenoma, 8 Hashimoto's thyroiditis, 7 papillary carcinoma and 10 normal thyroid specimens. Thyrocyte positivity for VEGF and VEGF receptors was scored 0,3. Immunohistochemistry for CD31, and CD34 on the same sections was performed to evaluate MVD. Immunohistochemical staining of VEGF in thyrocytes was positive in 92% of all the thyroid tissues studied. Using an immunostaining intensity cut off of 2, increased thyrocyte staining was seen in follicular adenoma specimens, MNG and normal thyroids compared with Hashimoto's thyroiditis and Graves' disease (P < 0.05). Similarly, VEGF thyrocyte expression in Graves' disease was less than other pathologies (P < 0.05). VEGFR-1 expression and the average MVD score did not differ between the different thyroid pathologies. VEGF expression was lower in autoimmune pathologies compared to autonomous growth processes. Conversely, both VEGFR-1 and VEGFR-2 were widely expressed in benign and neoplastic thyroid disease, suggesting that the up-regulation of VEGF and not its receptors occurs as tissue becomes autonomous. There was no clear relationship between MVD measurement and thyroid pathology. [source] Therapy of metastasized Merkel cell carcinoma with liposomal doxorubicin in combination with radiotherapyJOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT, Issue 6 2009Marion Wobser Summary Background: Merkel cell carcinoma is a rare skin cancer of neuroendocrine origin, which is characterized by a high rate of recurrence, metastatic spread and mortality. Because of its rarity, evidence-based therapeutic regimens are difficult to establish. Merkel cell carcinoma is known to be both radio- and chemosensitive. Toxicity is a key factor in assessing any regimen, as the patients are usually elderly and likely to have other significant medical problems. Patients and Methods: We retrospectively evaluated five patients with metastatic Merkel cell carcinoma to see if liposomal doxorubicin (Caelyx® or Myocet®) in combination with radiotherapy exhibited clinical anti-tumoral effects accompanied by acceptable side effects. Results: The outpatient chemotherapy regimen was tolerated without major side effects and produced good response rates. All patients achieved at least tumor stabilization; four of five had a partial remission. Effects of therapy were usually seen in the first cycle of therapy but the responses were of short duration with an average interval of two months until progression. Conclusions: As combined radiochemotherapy with liposomal doxorubicin is well tolerated even in older patients with other illnesses and can be given on an outpatient basis, it is an attractive option for metastatic Merkel cell carcinoma. Based on response rate or overall survival, it offers no advantages compared to polychemotherapy. [source] The role of the disintegrin metalloproteinase ADAM15 in prostate cancer progressionJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 6 2009Neali Lucas Abstract The metalloproteinase ADAM15 is a multi-domain disintegrin protease that is upregulated in a variety of human cancers. ADAM15 mRNA and protein levels are increased in prostate cancer and its expression is significantly increased during metastatic progression. It is likely that ADAM15 supports disease progression differentially through the action of its various functional domains. ADAM15 may downregulate adhesion of tumor cells to the extracellular matrix, reduce cell,cell adhesion, and promote metastasis through the activity of its disintegrin and metalloproteinase domains. Additionally, ADAM15 can influence cell signaling by shedding membrane-bound growth factors and other proteins that interact with receptor tyrosine kinases, leading to receptor activation. There is also evidence supporting a role for ADAM15 in angiogenesis and angioinvasion of tumor cells, which are critical for unrestrained tumor growth and metastatic spread. Given its diverse functions, ADAM15 may represent a pivotal regulatory component of tumor progression, an important target for therapeutic intervention, or emerge as a biomarker of disease progression. J. Cell. Biochem. 106: 967,974, 2009. © 2009 Wiley-Liss, Inc. [source] Molecular markers and determinants of prostate cancer metastasisJOURNAL OF CELLULAR PHYSIOLOGY, Issue 3 2001Rahul V. Gopalkrishnan Although intensely studied, the molecular and biochemical determinants of prostate cancer development and progression remain ill-defined. Moreover, current markers and methodologies cannot distinguish between a tumor that will remain indolent and not impinge on patient survival, versus a tumor with aggressive traits culminating in metastatic spread and death. Once prostate cancer is confirmed the most significant threat to a patient's survival and quality of life involves tumor metastasis. Radical surgery notwithstanding, prostate cancer accounts for 10% of all cancer-related deaths primarily arising through development of metastasis. Metastasis markers demonstrating an acceptable level of reliability are an obvious necessity if disproportionate and costly treatment is to be avoided and a reasonably accurate determination of clinical prognosis and measure of successful response to treatment is to be made. Therapeutic strategies that specifically inhibit metastatic spread are not presently possible and may not become available in the immediate future. This is because, while localized tumorigenesis has been relatively amenable to detection, analysis and treatment, metastasis remains a relatively undefined, complex and underexplored area of prostate cancer research. New findings in the field such subclasses of genes called metastasis suppressors and cancer progression suppressors, have opened up exciting avenues of investigation. We review current methodological approaches, model experimental systems and genes presently known or having potential involvement in human prostate cancer metastasis. © 2001 Wiley-Liss, Inc. [source] Leptomeningeal carcinomatosis from squamous cell carcinoma of the supraglottic larynxJOURNAL OF MEDICAL IMAGING AND RADIATION ONCOLOGY, Issue 3 2003Stephen R Thompson Summary Leptomeningeal carcinomatosis is an uncommon but devastating form of metastatic spread. To our knowledge, only 16 cases originating from a head and neck cancer have been reported. We describe the first case of a patient with leptomeningeal carcinomatosis arising from a laryngeal squamous cell carcinoma. Shortly after completing treatment for an advanced supraglottic laryngeal cancer, this 63-year-old man presented with lower limb neurological symptoms and signs. Radiological and cytological evidence of leptomeningeal carcinomatosis of the distal spinal canal was identified. He was treated with intrathecal methotrexate and palliative radiotherapy. Although his pain improved, his lower limb weakness worsened. He died 3 weeks after completing radiotherapy. Presumed mode of spread was via the haematogenous route. The natural history and management of leptomeningeal carcinomatosis are discussed. Clinicians should be aware of the uncommon possibility of leptomeningeal carcinomatosis in a patient presenting with an appropriate constellation of symptoms and signs, and a past history of cancer. [source] Prognostic significance of tumor shape and stromal chronic inflammatory infiltration in squamous cell carcinomas of the oral tongueJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 9 2010Ioulia Chatzistamou J Oral Pathol Med (2010) 39: 667,671 Background:, Squamous cell carcinoma (SCC) of the oral tongue is well known to be an aggressive disease with early metastatic spread in early stage tumors. It is also established that locoregional recurrences are the main causes of treatment failure. Thus, the identification of histopathological factors possessing a predictive value remains important for the management of the disease. The aim of the present study was to define histopathological parameters of the tumor and to compare with the follow-up and status in primary SCCs of the mobile tongue. Methods:, Histopathological parameters such as mitotic index, the presence of vascular emboli or perineural invasion, the thickness of the tumor, the histological grade, the tumor shape as well as chronic stromal inflammatory infiltration were assessed in 52 patients with SCC of the mobile tongue and compared with the follow-up and status in patients treated initially by surgery. Results:, Tumor shape was significantly associated with the presence of perineural invasion. Well-defined shaped tumors displayed almost half the incidence of perineural invasion when compared with ill-defined shaped tumors. In addition, the high density of the chronic inflammatory infiltration of the stroma exhibited significant correlation with the survival of the patients. Finally, the intense chronic inflammatory infiltration of the stroma was associated with well-defined shaped tumors. Conclusion:, Tumor shape and stromal chronic inflammatory infiltration should be considered in the planning of the management of patients with SCC of the mobile tongue. [source] The natural course of cutaneous melanomaJOURNAL OF SURGICAL ONCOLOGY, Issue 4 2004Ulrike Leiter MD Abstract The natural course of cutaneous melanoma (CM) is determined by its metastatic spread and depends on tumor thickness, ulceration, gender, localization, and the histologic subtype of the primary tumor. CM metastasis develops via three main metastatic pathways and occurs as satellite or in-transit metastasis, as regional lymph node metastasis or as distant metastasis at the time of primary recurrence. About 50% of all CM patients with tumor progression firstly develop regional lymph node metastases. In the other 50% the first metastases are satellite or in-transit metastases (about 20%), or immediately distant metastases (about 30%). Development of distant metastasis appears to be an early event in metastatic spread and may in the majority of cases originate from the primary tumor, only few cases may develop secondarily to locoregional metastasis. Reporting of organ involvement in distant metastasis greatly differs between the results of imaging techniques and autopsy results in respect to the metastatic patterns detected, pointing out that there is a need of improved imaging systems. Proliferation, neovascularization, lymphangiogenesis, invasion, circulation, and embolism are important steps in the pathogenesis of CM metastasis, with tumor vascularity as an important independent significant prognostic factor. The expression of chemokine receptors in cancer cells associated with the expression of the respective chemokine receptor ligands in the target sites of the metastasis is an interesting observation which may stimulate the development of new therapeutic strategies. J. Surg. Oncol. 2004;86:172,178. © 2004 Wiley-Liss, Inc. [source] Identification of markers for the selection of patients undergoing renal cell carcinoma-specific immunotherapyPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 6 2003Barbara Seliger Abstract Renal cell carcinoma (RCC) represents the most common malignant tumor in the kidney and is resistant to conventional therapies. The diagnosis of RCC is often delayed leading to progression and metastatic spread of the disease. Thus, validated markers for the early detection of the disease as well as selection of patients undergoing specific therapy is urgently needed. Using treatment with the monoclonal antibody (mAb) G250 as a model, proteome-based strategies were implemented for the identification of markers which may allow the discrimination between responders and nonresponders prior to application of G250-mediated immunotherapy. Flow cytometry revealed G250 surface expression in approximately 40% of RCC cell lines, but not in the normal kidney epithelium cell lines. G250 expression levels significantly varied thereby distinguishing between low, medium and high G250 expressing cell lines. Comparisons of two-dimensional gel electrophoresis expression profiles of untreated RCC cell lines versus RCC cell lines treated with a mAb directed against G250 and the characterization of differentially expressed proteins by mass spectrometry and/or Edman sequencing led to the identification of proteins such as chaperones, antigen processing components, transporters, metabolic enzymes, cytoskeletal proteins and unknown proteins. Moreover, some of these differentially expressed proteins matched with immunoreactive proteins previously identified by proteome analysis combined with immunoblotting using sera from healthy donors and RCC patients, a technique called PROTEOMEX. Immunohistochemical analysis of a panel of surgically removed RCC lesions and corresponding normal kidney epithelium confirmed the heterogeneous expression pattern found by proteome-based technologies. In conclusion, conventional proteome analysis as well as PROTEOMEX could be successfully employed for the identification of markers which may allow the selection of patients prior to specific immunotherapy. [source] Cancer type-specific tNOX isoforms: A putative family of redox protein splice variants with cancer diagnostic and prognostic potentialBIOFACTORS, Issue 3 2008D. James Morré A proteomics approach with detection on western blots using an S-peptide tagged pan-tNOX (ENOX2) recombinant (scFv) antibody followed by alkaline phosphatase-linked anti S has revealed a family of more than 20 ENOX2 isoforms of varying molecular weights (34 to 94 kDa) and mostly of low isoelectric points (4.6 ± 0.7) based on serum analysis. Different isoforms characterize cancers of different tissue origins indicative of both cancer presence and tissue site of origin. ENOX2 proteins are cancer-associated and differ from constitutive (CNOX or ENOX1) proteins primarily by the absence of a drug binding site to which the cancer-specific scFv is directed. All are located on the cell surface where they function both as terminal oxidases for plasma membrane electron transport and carry out protein disulfide-thiol interchange. These proteins are shed into the blood and can also be found in urine. The tNOX isoform technology is under development as a clinical aid to identify unknown or uncertain primary cancers, evaluation of metastatic spread in post surgery patients, monitoring remission following cessation of therapy and for early diagnosis in at-risk populations. [source] Metastatic pathways and time courses in the orderly progression of cutaneous melanomaBRITISH JOURNAL OF DERMATOLOGY, Issue 1 2002F. Meier SummaryBackground,,It is known that two-thirds of patients who develop clinical metastases following treatment of a primary cutaneous melanoma initially present with locoregional metastases and one-third initially present with distant metastases. However, few reports in the literature give detailed figures on different metastatic pathways in cutaneous melanoma. Objectives,,The aim of the present study was to perform a detailed analysis of the different metastatic pathways, the time course of the development of metastases and the factors influencing them. Methods,,In a series of 3001 patients with primary cutaneous melanoma at first presentation, 466 subsequently developed metastasis and were followed-up over the long term at the University of Tuebingen, Germany between 1976 and 1996. Different pathways of metastatic spread were traced. Associated risk factors for the different pathways were assessed. Differences in survival probabilities were calculated by the Kaplan,Meier method and evaluated by the log-rank test. Results,,In 50·2% of the patients the first metastasis after treatment of the primary tumour developed in the regional lymph nodes. In the remaining half of the patient sample the first metastasis developed in the lymphatic drainage area in front of the regional lymph nodes, as satellite or in-transit metastases (21·7%) or as direct distant metastases (28·1%). Anatomical location, sex and tumour thickness were significant risk factors for the development of metastasis by different pathways. The most important risk factor appeared to be the location of the primary tumour. The median intervals elapsing before the first metastasis differed significantly between the different metastatic pathways. The direct distant metastases became manifest after a median period of 25 months, thus later than the direct regional lymph node metastases (median latency period, 16 months) and the direct satellite and in-transit metastases (median latency period, 17 months). In patients who developed distant metastases the period of development was independent of the metastatic route. The time at which the distant metastases developed was roughly the same (between 24 and 30 months after the detection of the primary tumour), irrespective of whether satellite or in-transit metastases, lymph node metastases or distant metastases were the first to occur. Conclusions,,The time course of the development of distant metastasis was more or less the same irrespective of the metastatic pathway; this suggests that in patients with in-transit or satellite metastasis or regional lymph node metastasis, haematogenic metastatic spread had already taken place. Thus, the diagnostic value of sentinel lymph node biopsy and the therapeutic benefit of elective lymph node dissection may be limited, as satellite and in-transit metastases or direct distant metastases will not be detected and haematogenous spread may already have taken place when the intervention is performed. [source] Treatment of liver metastases from neuroendocrine tumours in relation to the extent of hepatic disease,BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 2 2009A. Frilling Background: Hepatic surgery is presumed to improve survival of patients with liver metastases (LM) from neuroendocrine tumours (NET). This study identified LM-specific variables that could be used as additional selection criteria for aggressive treatment. Methods: A novel classification of LM from NET was established based on their localization and presentation. Results: From 1992 to 2006, 119 patients underwent staging and treatment of LM. Three growth types of LM were identified radiologically: single metastasis (type I), isolated metastatic bulk accompanied by smaller deposits (type II) and disseminated metastatic spread (type III). The three groups differed significantly in terms of chronological presentation of LM, hormonal symptoms, Ki-67 index, 5-hydroxyindoleacetic acid and chromogranin A levels, lymph node involvement, presence of bone metastases and treatment options. The 3-, 5- and 10-year disease-specific survival rates for the entire cohort were 76·4, 63·9 and 46·5 per cent respectively. There were significant differences in survival between the three groups: 5- and 10-year rates were both 100 per cent for type I, 84 and 75 per cent respectively for type II, and 51 and 29 per cent for type III. Conclusion: The localization and biological features of LM from NET defines therapeutic management and is predictive of outcome. Copyright © 2009 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source] Prospective study of bone scintigraphy as a staging investigation for oesophageal carcinoma,BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 7 2008N. A. Jennings Background: About 10 per cent of patients undergoing radical oesophagectomy for transmural (T3) carcinoma with lymph node involvement (N1) develop symptomatic bone metastases within 12 months of surgery. The aim of this study was to evaluate the introduction of targeted preoperative bone scintigraphy. Methods: Of 790 patients with oesophageal carcinoma staged between December 2000 and December 2004, 189 were eligible for potentially curative treatment. 99mTc-labelled hydroxymethylene diphosphonate bone scintigraphy was performed in those with stage T3 N1 disease (identified by computed tomography and endoscopic ultrasonography) who were suitable for radical treatment. Results: A total of 115 patients had bone scintigraphy. The histological diagnosis was adenocarcinoma in 82 patients and squamous cell carcinoma in 33. Bone scintigraphy was normal or showed degenerative changes in 93 patients, and abnormal requiring further investigation in 22. Plain radiography, magnetic resonance imaging and biopsy confirmed the presence of bone metastases in 11 patients (9·6 per cent). Conclusion: Bone is frequently the first site of identifiable distant metastatic spread, and bone scintigraphy is recommended to exclude metastatic disease before radical treatment of advanced oesophageal carcinoma. Copyright © 2008 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source] A 5-decade analysis of 13,715 carcinoid tumorsCANCER, Issue 4 2003Irvin M. Modlin M.D., Ph.D. Abstract BACKGROUND Carcinoid tumors represent an unusual and complex disease spectrum with protean clinical manifestations. This compilation of several large United States-based databases comprising patients from 1950 to 1999 examines 13,715 carcinoid tumors and provides epidemiologic information regarding the natural history and evolution of the detection and diagnosis of this entity. METHODS The authors evaluated 10,878 carcinoid tumors that were identified by the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute (NCI) from 1973 to 1999 in addition to 2837 carcinoid tumors that were registered previously by two earlier NCI programs. To the authors' knowledge, this represents the largest current epidemiology series addressing carcinoid tumors to date. RESULTS Specific trends in incidence for carcinoid tumors of certain sites were identified. Among the most recently collected subset of data, sites that demonstrated the greatest incidence of carcinoids were the gastrointestinal tract (67.5%) and the bronchopulmonary system (25.3%). Within the gastrointestinal tract, most carcinoid tumors occurred in the small intestine (41.8%), rectum (27.4%), and stomach (8.7%). For all sites, age-adjusted incidence rates were highest in black males (4.48 per 100,000 population per year). Associated noncarcinoid tumors were frequent in conjunction with small intestinal (29.0%), gastric (20.5%), colonic (20.0%), and appendiceal (18.2%) carcinoids. The highest percentages of nonlocalized lesions were noted for cecal (81.5,83.2%) and pancreatic (71.9,81.3%) carcinoids, whereas the highest percentage of localized disease was found among rectal (81.7%), gastric (67.5%), and bronchopulmonary (65.4%) carcinoids. The best 5-year survival rates were recorded for patients with rectal (88.3%), bronchopulmonary (73.5%), and appendiceal (71.0%) carcinoids; these tumors exhibited invasive growth or metastatic spread in 3.9%, 27.5%, and 38.8% of patients, respectively. CONCLUSIONS Carcinoids appear to have increased in overall incidence over the past 30 years; for some sites, this trend has been evident for nearly half a century. Recent marked increases in gastric and rectal carcinoids and a concomitant decrease in appendiceal carcinoid incidence may be due in part to varying rules of registration among the compiled databases examined in this report or to improvements in diagnostic technology; increased awareness of and about carcinoid tumors also may play a significant role. In 12.9% of all patients with carcinoid, distant metastases already were evident at the time of diagnosis; the overall 5-year survival rate for all carcinoid tumors, regardless of site, was 67.2%. These findings bring into question the widely promulgated relative benignity of carcinoid disease. Certain carcinoid tumors, such as those of the rectum, appear to be over-represented among the black and Asian populations within the United States, suggesting the role of genetics in the development of this intriguing disease. Cancer 2003;97:934,59. © 2003 American Cancer Society. DOI 10.1002/cncr.11105 [source] Tumor carbonic anhydrase 9 expression is associated with the presence of lymph node metastases in uterine cervical cancerCANCER SCIENCE, Issue 3 2007Sun Lee Tumor hypoxia has a pronounced effect on malignant progression and metastatic spread of human tumors. As carbonic anhydrases (CA) 9 and 12 are induced by the low-oxygen environment within tumors, we investigated the relationship between the expression of these two CA and the presence of metastatic lymph nodes (LN) in uterine cervical cancer. CA9/CA12 expression was evaluated histochemically in primary cervical cancer tissues of 73 patients who underwent laparoscopic LN staging and two patients with clinical staging before definitive radiotherapy at the National Cancer Center, Korea. We also evaluated CA9 expression in 33 patients with pathologically confirmed metastatic LN. CA9 expression in the primary tumors was significantly associated with LN metastasis (P = 0.03) and poorer disease-free survival (relative risk, 6.1; 95% confidence interval, 1.3,28.3, P = 0.02, multivariate analysis), whereas CA12 expression did not show such a relationship. In addition, 21 of 24 metastatic LN revealed similar CA9 expression (P = 0.001), suggesting that CA9-expressing tumor cells had a higher metastatic potential. CA9 was expressed in 45 of 75 (60%) primary tumors, with positive tumor cells observed predominantly in the area away from the blood vessels. In contrast, CA12 expression was observed in only 29 of 74 primary tumors (39%), without a specific pattern. These findings indicate that expression of CA9, but not CA12, in tumors is associated with the presence of LN metastases and poorer prognosis. Selective application of new treatment modalities based on CA9 expression to prevent LN metastases may improve overall treatment outcome in patients with uterine cervical cancer. (Cancer Sci 2007; 98: 329,333) [source] 4262: MLPA of choroidal melanomaACTA OPHTHALMOLOGICA, Issue 2010BE DAMATO Purpose To determine the genotypic profiles of choroidal melanomas using multiplex ligation-dependent probe amplification (MLPA) and to correlate findings with clinical and pathological features and metastatic death. Methods DNA samples from 452 choroidal melanomas were analyzed with MLPA evaluating 31 loci on chromosomes 1, 3, 6 and 8. The MLPA results were correlated with survival predictors and wiht metastatic death. Results The patients (194 female; 258 male) had a median age of 59.4 years and a median follow-up of 1.89 years. Metastatic death occurred in 47 patients, correlating most strongly with concurrent chromosomes 3 losses and chromosome 8q gains (Logrank analysis, p<0.001). Many small choroidal melanomas with a basal diameter of less than 10mm showed only chromosome 3 loss or chromosome 8q gain or none of these, suggesting that their tumour was 'pre-lethal' at the time of ocular treatment. Conclusion MLPA analysis of choroidal melanoma is predictive of metastatic death and, therefore, clinically useful. The findings of this study are most consistent with evolutionary clonal abnormality, suggesting that timely treatment prevents the metastatic genotype and metastatic spread in a proportion of patients. [source] 4265: Inhibitory isoforms of VEGF in uveal melanomaACTA OPHTHALMOLOGICA, Issue 2010SE COUPLAND Purpose Uveal melanoma (UM) affects around 600 new patients in the UK each year with half of these being treated at the Liverpool Ocular Oncology Centre. UM is an unusual tumour in that gross chromosomal abnormalities are strongly associated with metastatic spread, especially monosomy 3 & chromosome 8q gain. Mechanisms that underlie this remain unclear. Methods Angiogenesis is a requirement for tumour survival & metastasis. Vascular Endothelial Growth Factor (VEGF) is known to be the most potent stimulator of angiogenesis and increased expression of VEGF-A is linked to enhanced metastatic potential in UM. Treatment with bevacizumab (anti-VEGF therapy) suppresses hepatic micrometastasis of ocular melanoma cells in animal models. However, VEGF-A data in UM are variable, with some studies demonstrating no correlation between VEGF-A expression and metastasis or survival. Results VEGF-A was accepted as a single pro-angiogenic family of protein isoforms generated from alternatively spliced mRNA (VEGF189, VEGF165 etc). However, recently a family of sister isoforms named VEGFxxxb, where xxx is the amino acid number and b a different six C-terminus amino acids (VEGF189b, VEGF165b) has been discovered. The VEGFxxxb variants are exactly the same size as pro-angiogenic VEGFxxx, yet are antiangiogenic. VEGF165b is down-regulated in primary cutaneous melanoma that later metastasises, and over-expression of VEGFxxxb isoforms confers a protective anti-tumour effect. Conclusion Immunohistochemical expression of pro- and anti-angiogenic VEGF-A in 19 UM was assessed using pan-VEGF-A and VEGF165b specific antibodies. A statistically significant reduction in expression of VEGF165b was observed in monosomy 3 UM (non-parametric ANOVA; p<0.05). This suggests that VEGF165b expression may be a useful predictor of UM metastasis. [source] Tumour-associated angiogenesis in human colorectal cancerCOLORECTAL DISEASE, Issue 1 2007K. A. Rmali Abstract Tumour angiogenesis is a critical step in the growth, metastatic spread and regrowth of colorectal cancer. Angiogenesis specific to tumour is a complicated process, the mechanisms of which remain unclear. Metastasis of colorectal cancer may result from passive entry into the circulation secondary to the effect of angiogenic factors. The survival and growth of colorectal tumour and thus their metastases are dependent on the balance of endogenous angiogenic and anti-angiogenic factors such that the outcome favours increased angiogenesis. Angiogenesis has become an attractive target for anticancer drug development, based on its important roles in tumour growth, invasion and metastasis. Several growth factors have been identified that regulate angiogenesis in colorectal cancer; the most important of these are vascular endothelial growth factors (VEGF), and of the several angiogenic factors, VEGF expression at the deepest invasive site of tumour is the most statistically significant prognostic indicator in advanced colorectal carcinoma. In this review article, we provide an overview on angiogenic factors and their receptors, and discuss the role of newly identified tumour endothelial markers (TEMs) that are involved in tumour-associated angiogenesis in colorectal cancer. [source] | ||||||||||||||||||||||||||||