• 69 patients with nonmetastatic colorectal cancer (non-mCRC) and 57 with metastatic CRC (mCRC) were enrolled to evaluate the prognostic value of serum albumin (ALB), serum lactate (SLA), and lactate dehydrogenase (LDH) in patients with metastatic CRC. (hindawi.com)
  • Distant metastasis is the main cause of the treatment failure of the patients with colorectal cancer. (hindawi.com)
  • In the literature, CEACAM5 is often used as a synonym for cancer embryonic antigen (CEA), a well-known biomarker of many types of malignancies, such as colorectal cancer and non-small-cell lung cancer. (wikipedia.org)
  • Conclusion: Lymphatic invasion in colorectal cancer correlates well with the status of lymph node metastasis and disease stage, representing an independent prognostic factor after curative resection. (iiarjournals.org)
  • Although the prognostic import of lymph node metastasis is widely accepted in colorectal cancer, 12 nodes or more must be examined to adequately assess the degree of lymph node metastasis ( 5 , 6 ). (iiarjournals.org)
  • The present study examined correlations between lymphatic invasion and lymph node metastasis or disease stage, and clarified the prognostic impact of lymphatic invasion, based on a large series and long-term follow-up of patients with colorectal cancer curatively treated. (iiarjournals.org)
  • Colorectal cancer (CRC) frequently harbors KRAS mutations that result in chemoresistance and metastasis. (thno.org)
  • The epidermal growth factor receptor (EGFR)/RAS/RAF/MEK/MAPK pathway plays a crucial role in the carcinogenesis, invasion and metastasis of colorectal cancer (CRC). (oncotarget.com)
  • In this study, we investigated the role of galectin-3 and carcinoembryonic antigen (CEA) in metastasis and survival of colorectal cancer (CRC) patients. (oncotarget.com)
  • A total of 2226 deter- or regression status in breast cancer cological (lung, colorectal, pancreas minations of serum CEA and CA15-3 patients [5-8]. (who.int)
  • Lymph node metastasis is an important factor for predicting the prognosis of colorectal cancer patients. (e-crt.org)
  • Serum and tissue markers in colorectal cancer: State of art. (novodiax.com)
  • Carcinoembryonic antigen is the preferred biomarker for in vivo colorectal cancer targeting. (novodiax.com)
  • This was found in the serum of a patient with colorectal carcinoma. (labpedia.net)
  • Thus this CEA antigen was considered the indicator of colorectal cancers. (labpedia.net)
  • The presence of multiple types of metastases or peritoneal metastases in colorectal cancer is defined as stage IVb or IVc, respectively, in the eighth edition of the American Joint Committee on Cancer tumor-node-metastasis staging system because of its poorer prognosis than stage IVa [ 1 ]. (coloproctol.org)
  • Although minimally invasive surgery is prevalent for the treatment of colorectal cancer, its use in patients with synchronous distant lymph nodes or peritoneal metastases has rarely been reported. (coloproctol.org)
  • This video presents the procedural details of laparoscopic right hemicolectomy with aortocaval lymphadenectomy, partial resection of the pelvic peritoneum, and hyperthermic intraperitoneal chemotherapy (HIPEC) for a patient with colorectal cancer and synchronous distant metastases, for which neoadjuvant chemotherapy was used ( Supplementary Video 1 ). (coloproctol.org)
  • Improving resectability of hepatic colorectal metastases: expert consensus statement. (cancercentrum.se)
  • Univariate and multivariate analyses were performed by the logistic regression procedure to determine the relationship between pathological lymph node metastasis-positive status and clinical or radiological findings such as the maximum dimensions of consolidation and the tumour, the presence of air bronchogram, pleural indentation and the preoperative serum carcinoembryonic antigen (CEA) level. (nih.gov)
  • Age and sex of patients, site, gross type, size (maximum tumor diameter), preoperative serum level of carcinoembryonic antigen (CEA), depth of wall invasion, status of lymph node metastasis, histopathological differentiation, degree of lymphatic and venous invasion, and presence or absence of postoperative adjuvant chemotherapy were extracted from operation records and pathology reports. (iiarjournals.org)
  • 0.001) and preoperative serum carcinoembryonic antigen (CEA) level (p = 0.017) are independent risk factors lymph node metastasis in cN0 NSCLC. (biomedcentral.com)
  • Tumor consolidation diameter and preoperative serum CEA are independent factors to predict cN0 NSCLC with tumor size ≤ 30 mm. (biomedcentral.com)
  • ABSTRACT The value of serum tumour markers in the prognosis of patients with breast cancer is controversial. (who.int)
  • This prospective study in Yazd, Islamic Republic of Iran, assessed the value of the tumour markers carcinoembryonic antigen (CEA) and cancer antigen (CA) 15-3 in 159 patients with primary breast cancer. (who.int)
  • sis in primary breast cancer patients, toms of metastasis or recurrence and Tumour markers assays with elevated levels reflecting adverse with no other malignant disorders. (who.int)
  • To identify the population of patients with high risk of distant metastasis and the poor prognosis before treatment, so as to provide early intervention and better treatment decision. (hindawi.com)
  • HR, 3.94) were associated with worse prognosis in cases without and with metastasis, respectively. (bvsalud.org)
  • The most frequent tumor suppressor miRs were miR-126, miR-199b and miR-22 and the hypoexpression of these miRs was associated with distant metastasis, worse prognosis and a higher risk of disease relapse (worse disease-free survival). (biorxiv.org)
  • Serum carcinoembryonic antigen and cytokeratin 19 were abnormally highly expressed in non-Small cell lung cancer patients, which are useful for clinical diagnosing, treatment planning, efficacy monitoring, and prognosis evaluation. (ijpsonline.com)
  • Whether in the early diagnosis of tumor, in the monitoring of metastasis and recurrence or in the evaluation of efficacy and prognosis, tumor markers were very important clinical reference indicators[ 4 , 5 ]. (ijpsonline.com)
  • Many studies showed that the carcinoem-bryonic antigen (CEA) and human cytokeratin fragment antigen 21-1 (CYFRA21-1) has a high value in predicting tumor recurrence and judging the prognosis of patients[ 2 , 3 ]. (ijpsonline.com)
  • Therefore, the purpose of this paper was to determine whether lymph node metastasis represents a complementary method to the TNM stage method for accurate prediction of prognosis (the number of lymph node metastases) in patients who did not receive adequate lymph node evaluation. (e-crt.org)
  • Leptomeningeal metastases (LM) occur in 3- 5% of patients with advanced non-small-cell lung cancer (NSCLC) and are associated with a dismal prognosis. (dovepress.com)
  • Goal: To explore risk factors for lymph node metastases in early gastric malignancy (EGC) and to confirm the appropriate range of lymph node dissection. (bioskinrevive.com)
  • Binary logistic regression analysis was applied to predict risk factors for lymph node metastasis, and subject operating characteristics (ROC) curve was used to evaluate the independent risk factors. (biomedcentral.com)
  • We selected cN0 NSCLC patients with tumor diameter ≤ 30 mm and without imaging metastatic lymph nodes before surgery to study the incidence and risk factors for lymph node metastasis, thereby to provide the surgical indications for lymph node dissection in cN0 NSCLC. (biomedcentral.com)
  • Table 3 Multivariate analysis of lymph node metastases in early gastric malignancy for the entire study population Relationship between depth of invasion and quantity of metastatic lymph nodes There was no significant difference between mucosal and submucosal tumors in terms of quantity of retrieved lymph nodes, using the self-employed sample test (= 0.350, df = 200, = 0.727, mean difference = 0.534). (bioskinrevive.com)
  • In this system, stages are assigned on the basis of the characteristics of the primary tumor (T) and the extent of regional lymph node involvement (N) and distant metastasis (M). In addition, metastasis may be defined clinically or pathologically, on the basis of preoperative clinical assessment (c) or pathologic evaluation of metastatic tissue (p). (medscape.com)
  • Additionally, a deeper understanding of the metastatic cascade in breast cancer will be critical for developing therapeutic interventions to combat breast cancer metastasis. (iiarjournals.org)
  • CTCs are recognized as playing important roles in the metastasis of carcinomas ( 11 , 12 ) and their analysis enables the prediction of metastatic relapse and progression ( 11 ). (iiarjournals.org)
  • Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) also known as CD66e (Cluster of Differentiation 66e), is a member of the carcinoembryonic antigen (CEA) gene family. (wikipedia.org)
  • Positive EGFR expression and an abnormal postoperative serum carcinoembryonic antigen (CEA) level were found to be significant independent negative predictive factors for postoperative relapse. (oncotarget.com)
  • And the comparison between postoperative ePD-L1 and conventional serum biomarkers (carcinoembryonic antigen (CEA), cancer antigen 19-9 (CA19-9) and CA72-4) in prognostic of GC patients was made. (bmj.com)
  • Results The prognostic value of postoperative ePD-L1 is superior to that of preoperative ePD-L1 on GC patients after resection, and also superior to that of conventional serum biomarkers (CEA, CA19-9 and CA72-4). (bmj.com)
  • A 51-year-old woman with pathological stage IIA adenocarcinoma with trophoblastic differentiation underwent left lower lobectomy with lymph node dissection and postoperative adjuvant chemotherapy, remaining tumor-free for 10 months until the detection of the brain metastasis. (journalmc.org)
  • 6 ) emphasized that the inclusion of serum tumor markers is an important factor in the postoperative monitoring of breast cancer patients ( 7 , 8 ). (iiarjournals.org)
  • Another suggestion is to have intensive postoperative follow-up which includes consultations every 4-6 months, physical examination and evaluation of serum carcinoembryonic antigen (CEA), tissue polypeptide antigen (TPA) and breast cancer-associated antigen 115 D8/DF3 (CA15.3), at each visit. (iiarjournals.org)
  • The tissue which is found in embryonic tissue is called carcinoembryonic antigen (CEA). (labpedia.net)
  • CEA is a tumor-associated, oncofetal antigen seen in embryonic and fetal tissue. (labpedia.net)
  • Unusual carcino-embryonic antigen (CEA) degree of 50.93?ng/mL (0C10?ng/mL) and an elevated neuron-specific enolase (NSE) degree of 4.26?ng/mL (0C3.3?ng/mL) were observed. (mingsheng88.org)
  • The first alpha-globulins to appear in mammalian sera during development of the embryo and the dominant serum proteins in early embryonic life. (curehunter.com)
  • The purpose of this study is to investigate risk factors of lymph node metastasis in cN0 NSCLC, thereby to identify the surgical indications for lymph node dissection in cN0 NSCLC. (biomedcentral.com)
  • 16.5 mm, the probability of lymph node metastasis is higher and lymph node dissection is recommended. (biomedcentral.com)
  • This antibody has a high affinity for CEA and shows no detectable reactivity to nonspecific cross-reacting antigen (NCA), biliary glycoprotein (BGP) and human polymorphonuclear leucocytes. (samatashkhis.com)
  • The mechanisms of recurrence and metastasis of CRC are very complicated and remains unclear. (biomedcentral.com)
  • Recurrence and metastasis may involve series of cell biological behaviors, including circulating tumor cells (CTCs), which have been gradually recognized to play an important role in the process of distant metastasis, according to the "seed and soil theory" [ 5 ]. (biomedcentral.com)
  • Radical nephrectomy and nephron-sparing surgery are still the only effective treatments for localized RCC, but the characteristics of RCC recurrence and metastasis lead to a 5-year survival rate of approximately 12%, posing a great challenge to clinical therapies [ 4 ]. (biomedcentral.com)
  • Compared with the clinical monitoring techniques of Computed tomography (CT), Positron emission tomography computed tomography (PET-CT), and specific biomarkers, the detection of serum tumor markers was more simple, rapid and less invasive and has important clinical application value[ 6 - 9 ]. (ijpsonline.com)
  • In this review we discuss the current knowledge in the area of peripheral immune-based biomarkers, drawing information from the results of recent clinical studies of a number of different immunotherapy modalities in the treatment of cancer, including checkpoint inhibitors, bispecific antibodies, chimeric antigen receptor T cells, and anti-cancer vaccines. (biomedcentral.com)
  • During follow-up, 33 patients (20.8%) presented symptomatic metastasis. (who.int)
  • Aim: To determine correlations between lymphatic invasion and lymph node metastasis or disease stage, and clarify the prognostic impact of lymphatic invasion. (iiarjournals.org)
  • Survival was compared between different degrees of lymphatic invasion and lymph node metastasis. (iiarjournals.org)
  • It is well-known that not only the presence or absence of lymph node metastasis, but also the degree of presence, is an important prognostic factor, along with depth of tumor invasion, and is useful in determining the adjuvant chemotherapy and surveillance program ( 3 , 4 ). (iiarjournals.org)
  • In individuals with submucosal cancers, the lymph node metastases rate in individuals with venous invasion (60%, 3/5) was higher than in those without invasion (20%, 15/75) (2 = 4.301, = 0.038). (bioskinrevive.com)
  • Multivariate logistic regression analysis Selumetinib revealed the depth of invasion was the only self-employed risk element Selumetinib for lymph node metastases in EGC [= 0.018, Exp (B) = 2.744]. (bioskinrevive.com)
  • Univariate analysis of variance exposed a detailed relationship between the depth of invasion and lymph node metastases at pN1 (= 0.008). (bioskinrevive.com)
  • Summary: The depth of invasion was the only self-employed risk element for lymph node metastases. (bioskinrevive.com)
  • In individuals with submucosal cancers, there was no significant difference in the event of lymph node metastases in relation to sex, age, tumor location, tumor size, quantity of retrieved lymph nodes, morphological classification, histological type, lymphatic invasion, nervous invasion and CEA levels. (bioskinrevive.com)
  • Multivariate analysis of lymph node metastases in EGC Multivariate analysis revealed the depth of invasion was an independent risk element for lymph node metastases [= 0.018, Exp (B) = 2.744]. (bioskinrevive.com)
  • miR-139-5p overexpression inhibited CRC cell proliferation, migration and invasion in vitro , sensitized tumors to chemotherapy, and impaired tumor growth and metastasis in vivo . (thno.org)
  • On univariate analysis, the presence of nodules in the primary tumour, clinical lymph node swelling, elevated serum carcinoembryonic antigen (CEA) levels, tumour invasion level and lymph node metastasis were significant prognostic factors. (vgrd.org)
  • On multivariate analysis, invasion level and elevated serum CEA were the only factors that were significantly associated with reduced survival. (vgrd.org)
  • CONCLUSIONS: Invasion level and lymph node metastasis are important prognostic factors in EMPD. (vgrd.org)
  • Intraoperatively, we did not find tumor invasion to adjacent organs, peritoneal dissemination, or liver metastasis. (biomedcentral.com)
  • CEACAM6 promoted oral squamous cell carcinoma cell invasion, migration, cytoskeletal rearrangement, and metastasis via interaction with EGFR and enhancing it activation. (cusabio.cn)
  • Studies provide evidence that dysregulated overexpression of CEACAM6 plays a role in several of the hallmarks of cancer, including uncontrolled proliferation, anoikis resistance, immune evasion, invasion and metastasis. (cusabio.cn)
  • The recent American Joint Committee on Cancer (AJCC) manual also recognizes the following prognostic factors: preoperatively elevated serum carcinoembryonic antigen, satellite tumor deposit, tumor regression grade, circumferential resection margin, microsatellite instability, perineural invasion and KRAS mutational status [ 1 ]. (e-crt.org)
  • Hypoxia is considered a critical contributor to renal cell carcinoma progression, including invasion and metastasis. (biomedcentral.com)
  • However, the potential mechanisms by which it promotes invasion and metastasis have not yet been clarified. (biomedcentral.com)
  • Carcinoembryonic antigen (CEA) assay. (cancer.gov)
  • The results of non-smoker females with primary CA15-3) suspicion of symptomatic serum CEA assay can reflect progno- breast cancer, without signs or symp- metastasis. (who.int)
  • A cancer antigen (CA) 19-9 assay, if available, may also be useful to monitor the disease. (medscape.com)
  • The roles of miR-139-5p in CRC cells with and without KRAS mutation were determined by Cell Counting Kit-8 (CCK-8), colony formation, flow cytometry and transwell assays in vitro and by tumorigenesis and metastasis assays in vivo . (thno.org)
  • Lessons: To the very best of our understanding, this is actually the initial report of the PEComa from the rectum with liver organ metastases treated with just surgical resection. (cell-signaling-pathways.com)
  • These cells, which shed intermittently from the solid tumors, circulate in the bloodstream, and arrive at different positions, are the main cause of distant metastases [ 8 ]. (biomedcentral.com)
  • This patient series included those who underwent primary tumor resection, a bypass or a proctostomy and those who underwent the simultaneous resection of metastases with curative intent. (scirp.org)
  • In the cases of lung metastasis, metachronous resection was performed. (scirp.org)
  • A 47-year-old Chinese female patient without a smoking history was preliminarily diagnosed with right lung cancer with suspected multiple liver and bone metastasis. (frontiersin.org)
  • Imaging studies in- was one of the first serum-based tu- The study sample was women with cluding chest X-rays, liver ultrasonog- mour markers to be characterized, primary breast cancer attending a pri- raphy and bone scans were performed and its utility has been assessed in vate clinic in Yazd, Islamic Republic if there was clinical or laboratory a variety of malignancies including of Iran. (who.int)
  • Solitary liver metastasis in the S2/3 segment was detected 26 months after initial surgery. (biomedcentral.com)
  • Our experience suggests that HAIC should be considered as a treatment option in patients with resectable liver metastasis from gastric cancer. (biomedcentral.com)
  • However, further studies are needed to verify the validity of HAIC for resectable liver metastasis from gastric cancer. (biomedcentral.com)
  • however, the treatment strategy for liver metastasis of gastric cancer has not yet been established. (biomedcentral.com)
  • Here, we report a case of complete remission for more than 12 years following hepatic arterial infusion chemotherapy (HAIC) in a patient with solitary metachronous liver metastasis from gastric cancer. (biomedcentral.com)
  • To the best of our knowledge, the present case is the longest survivor of liver metastasis from gastric cancer who was treated with HAIC without surgery. (biomedcentral.com)
  • The results are often normal, even in patients with metastases to the liver. (medscape.com)
  • mass within the liver organ with suspected liver organ metastasis. (cell-signaling-pathways.com)
  • Background: The degree of lymph node metastasis represents an important prognostic factor for cancer. (iiarjournals.org)
  • Lymph node metastasis (N stage) is the single most important prognostic factor in CRC [ 2 ]. (e-crt.org)
  • RESULTS Univariate analysis of lymph node metastases in EGC and clinicopathological factors Univariate analysis was performed on the relationship between lymph node metastases and clinicopathological factors. (bioskinrevive.com)
  • Of the 398 patients, 59 (14.8%) had pathological lymph node metastasis. (nih.gov)
  • The T test, Chi square test, Kaplan-Meier survival analysis model, and Multivariate Cox proportional hazards regression model were applied to assess the prognostic significance of SLA, LDH, and serum ALB on the patients with mCRC. (hindawi.com)
  • Thirteen of the 76 patients (17%) developed systemic metastases and 10 of these died of disease. (vgrd.org)
  • In additon, advanced stage CRC patients had higher serum galectin-3 and CEA levels than early stage CRC patients. (oncotarget.com)
  • High serum CEA and galectin-3 levels correlated with advanced N stage and poor survival in CRC patients. (oncotarget.com)
  • These findings suggest interaction between galectin-3 and CEA promotes CRC migration and metastasis, and correlates with poor survival of CRC patients. (oncotarget.com)
  • It is difficult to determine the lymph node metastasis of patients with clinically negative lymph nodes (cN0) non-small cell lung cancer (NSCLC) before surgery. (biomedcentral.com)
  • Overall, 44 patients (6.8%) with cN0 NSCLC had lymph node metastasis. (biomedcentral.com)
  • For patients with tumor parenchyma ≤ 16.5 mm, the probability of lymph node metastasis is lower and lymph node sampling is feasible. (biomedcentral.com)
  • This study aims to investigate the factors that can predict cN0 NSCLC lymph node metastasis, including basic characteristics of patients, imaging characteristics and preoperative examination of some hematological indicators. (biomedcentral.com)
  • Several studies have We excluded patients who had other In the present study CEA and CA15-3 shown that changes in the CEA serum disorders that could affect the serum levels were measured from patients' level might be linked to progression level of CEA or CA15-3, whether on- serum sample. (who.int)
  • The most frequent oncogenic miRs investigated were miR-21, miR-181a, miR-182, miR-183, miR-210 and miR-224 and the hyperexpression of these miRs was associated with distant metastasis, lymph node metastasis and worse survival in patients with CRC. (biorxiv.org)
  • In this study, we extended the prognostic analysis to CRC patients with metastasis who underwent surgery in order to select the predictive factors from these available and inexpensive laboratory data. (scirp.org)
  • Nursing based on oxygen administration decreased the value of renal function indexes, serum inflammatory factors, and tumor markers in renal cell carcinoma patients. (biomedcentral.com)
  • Emerging techniques using the analysis of circulating tumor cells show promising results in predicting and identifying the early stages of breast cancer metastasis in patients. (iiarjournals.org)
  • CTCs are tumor cells originating from primary sites or metastases that circulate in the patients' bloodstream and are very rarely found in healthy individuals ( 9 , 10 ) ( Figure 1 ). (iiarjournals.org)
  • 7 Erlotinib is more widely used to treat patients with central nerve system (CNS) metastases including LM because of its better penetration of brain-blood barriers (BBB) than gefitinib and icotinib. (dovepress.com)
  • Results: During a median follow-up duration of 24 months, two patients died of disease progression, and 11 experienced recurrent tumors (eight intrathoracic tumors, two distant metastasis, and one both types of recurrences). (iiarjournals.org)
  • This test can be done on peritoneal fluid and CSF if it is raised to indicate tumor metastasis. (labpedia.net)
  • The minimally invasive approach was safe and feasible in this highly selected patient with colon cancer, aortocaval lymph nodes, and peritoneal metastases. (coloproctol.org)
  • A 60-year-old man was diagnosed with ascending colon cancer, and synchronous aortocaval lymph node (intrarenal aortic bifurcation) and peritoneal (single nodule at the rectovesical fossa) metastases were found on both abdominopelvic and chest computed tomography (CT) and 18-fluoro-deoxyglucose positron emission tomography CT scans ( Fig. 1 ). (coloproctol.org)
  • Cancer and Metastasis Reviews. (wikipedia.org)
  • Colon cancer is staged using the American Joint Committee on Cancer (AJCC) tumor/node/metastasis (TNM) classification and staging system. (medscape.com)
  • The inclusion criteria were (abnormal serum levels of CEA or breast cancer [1-3]. (who.int)
  • Breast cancer metastasis accounts for the majority of deaths from breast cancer. (iiarjournals.org)
  • Detection of breast cancer metastasis at the earliest stage is important for the management and prediction of breast cancer progression. (iiarjournals.org)
  • In this review, the current and novel methods for detection of breast cancer metastasis, as well as the mechanisms involved in metastasis and the treatment of breast cancer metastasis, are discussed. (iiarjournals.org)
  • The majority of deaths from breast cancer are not due to the primary tumor itself, but are the result of metastasis to other organs in the body ( 2 ). (iiarjournals.org)
  • Currently, detection of breast cancer metastasis relies on clinical manifestations of the spread to distant organs, biopsies of affected organs, radiological evaluations, imaging methods and serum tumor markers ( 3 , 4 ). (iiarjournals.org)
  • CEA is increased by 60% to 90% of metastasis of lung cancer. (labpedia.net)
  • Serum CEA levels rapidly decreased, and CT scan showed disappearance of the tumor with complete clinical response 8 months after HAIC. (biomedcentral.com)
  • Although mammographic screening has reduced the mortality rate associated with metastasis as a result of early diagnosis ( 2 ), the methods described above are frequently inept at detecting metastasis at the earliest stage and at accurately predicting the clinical outcome of the disease ( 3 , 4 ). (iiarjournals.org)
  • A significant relationship was seen between metastasis status and positive CEA and CA15-3 levels. (who.int)
  • The levels of serum tumor markers were detected by electrochemiluminescence immunoassay. (ijpsonline.com)
  • Bone tissue scintigraphic imaging demonstrated multiple bone tissue metastases. (mingsheng88.org)
  • Abdominal computed tomography of the patient revealed irregular wall thickening extending from the gastric body to the antrum, with no remarkable findings such as metastasis and infiltration of the lymph nodes or peripheral tissues ( Fig. 1 ). (e-ce.org)
  • No distant metastasis was detected by abdominal CT, brain MRI and bone scintigraphy. (journalmc.org)
  • Most early-stage NSCLC has no suspicious lymph node metastases and is identified as clinically negative lymph nodes (cN0) NSCLC. (biomedcentral.com)
  • However, whether these inflammatory laboratory parameters have a predictive effect on the metastasis of NSCLC lymph nodes has been rarely reported. (biomedcentral.com)