Use Of Serum Markers Research Articles

Surgical Experience and Functional Outcomes after Laparoscopic and Robot-Assisted Partial Nephrectomy: Results from a Multi-Institutional Collaboration

Background: In patients treated with partial nephrectomy, prior evidence showed that peri-operative outcomes, such as complications and ischemia time, improved as a function of the surgical experience of the surgeon, but data on functional outcomes after surgery are still scarce. Methods: We retrospectively analyzed data of 4011 patients with a single, unilateral cT1a-b renal mass treated with laparoscopic or robot-assisted partial nephrectomy. The operations were performed by 119 surgeons at 22 participating institutions between 1997 and 2022. Multivariable models investigated the association between surgical experience (number of prior operations) and acute kidney injury (AKI) and recovery of at least 90% of baseline estimated glomerular filtration rate (eGFR) 1 yr after partial nephrectomy. The adjustment for case mix included age, Body Mass Index, preoperative serum creatinine, clinical T stage, PADUA score, warm ischemia time, pathologic tumor size, and year of surgery. Results: A total of 753 (19%) and 3258 (81%) patients underwent laparoscopic and robot-assisted partial nephrectomy, respectively. Overall, 37 (31%) and 55 (46%) surgeons contributed only to laparoscopic and robotic learning curves, respectively, whereas 27 (23%) contributed to the learning curves of both approaches. In the laparoscopic group, 8% and 55% of patients developed AKI and recovered at least 90% of their baseline eGFR, respectively. After adjusting for confounders, we did not find evidence of an association between surgical experience and AKI after laparoscopic partial nephrectomy (odds ratio [OR]: 0.9992; 95% confidence interval [CI]: 0.9963, 1.0022; p = 0.6). Similar results were found when 1-year renal function was the outcome of interest (OR: 0.9996; 95% CI: 0.9988, 1.0005; p = 0.5). Among patients who underwent robot-assisted partial nephrectomy, AKI occurred in 11% of patients, whereas 54% recovered at least 90% of their baseline eGFR. On multivariable analyses, the relationship between surgical experience and AKI after surgery was not statistically significant (OR: 1.0015; 95% CI: 0.9992, 1.0037; p = 0.2), with similar results when the outcome of interest was renal function one year after surgery (OR: 1.0001; 95% CI: 0.9980, 1.0022; p = 0.9). Virtually the same findings were found on sensitivity analyses. Conclusions: In patients treated with laparoscopic or robot-assisted partial nephrectomy, our data suggest that the surgical experience of the operating surgeon might not be a key determinant of functional recovery after surgery. This raises questions about the use of serum markers to assess functional recovery in patients with two kidneys and opens the discussion on what are the key steps of the procedure that allowed surgeons to achieve optimal outcomes since their initial cases.

Identification of Helicobacterpylori-related gastric cancer risk using serological gastritis markers and endoscopic findings: a large-scale retrospective cohort study

BackgroundGastric cancer remains a severe public health problem worldwide, particularly in Japan. Recent studies have demonstrated that serum markers are beneficial for risk stratification in gastric cancer development. We aimed to evaluate the usefulness of serum markers either alone or in combination (serum markers plus endoscopy) for effective risk stratification of gastric cancer development.MethodsWe enrolled 22,736 patients aged 20–95 years who underwent blood sampling and endoscopic examination at Hiroshima University Hospital in Japan between 1990 and 2014. The serum pepsinogen (PG) levels and anti-Helicobacter pylori antibody (Hp-Ab) titers were evaluated in each patient. The enrolled patients were matched with the database of the Hiroshima Prefecture Regional Cancer Registry. We processed the medical records and excluded patients with possible confounding factors for PG levels, such as proton pump inhibitor use, prior successful eradication therapy, post-gastrectomy, severe hepatorenal dysfunction, Zollinger–Ellison syndrome, and autoimmune gastritis. Among the remaining 5131 patients, we reviewed records of endoscopic examinations and selected 1507 patients (mean age, 62.5 years; 985 men and 522 women) who underwent endoscopic examination more than three months after blood sampling.First, based on the ABC method, patients were classified as follows: High PG levels and negative Hp-Ab, group A, high PG levels and positive Hp-Ab, group B, low PG levels and positive Hp-Ab, group C, and low PG levels and negative Hp-Ab, group D. Group A was further classified into two subgroups using endoscopic findings: true A without atrophic gastritis and pseudo A with atrophic gastritis. All patients underwent annual endoscopy follow-up.ResultsAmong the 1,507 patients (mean age, 62.5 years; 985 men), 24 were diagnosed with newly developed gastric cancer. No significant difference in cancer development was found between group A (PG negative and Hp-Ab negative) and the other groups. Remarkably, no true A group subjects developed gastric cancer.ConclusionsThe combination of serum markers and endoscopic findings is essential for the risk evaluation of gastric cancer.

Analysis of the sensitivity and specificity of ultrasound elastometry of the liver in women with chronic hepatitis C

Introduction. Despite the success in the treatment of chronic hepatitis C (HCV), the incidence of HCV remains at a high level, and the assessment of the degree of liver fibrosis is relevant in all patients with HCV.The aim of the study was to conduct a comparative diagnosis of the stages of liver fibrosis in women with chronic hepatitis C according to ultrasound elastometry and biopsy.Materials and Methods. To achieve this goal, a comprehensive clinical, laboratory (including virological), instrumental examination of 93 patients with HCV of reproductive age was conducted.Results. When interpreting the results, it was found that ultrasound elastometry in women with chronic hepatitis C is comparable to the results of percutaneous puncture liver biopsy.Discussion. Chronic hepatitis causes significant economic damage to health systems. The main factor affecting the reduction of morbidity and the risk of complications is the early diagnosis of HCV infection and timely antiviral therapy. The main objective of therapy is to achieve a stable virological response (SVR), as well as to reduce the activity of inflammation and the stage of AF in patients with HCV. The isolated use of serum markers of fibrosis and ultrasound elastometry of the liver at the early stages of the disease is not informative enough, so it is advisable to use a combination of different techniques, and at the CP stage, a puncture biopsy can be safely replaced with ultrasound elastometry of the liver, especially for the purpose of dynamic monitoring of patients with HCV.Conclusion. According to the comparative ROC-analysis of the results of ultrasound elastography and puncture liver biopsy, the high sensitivity and specificity of these methods for diagnosing liver fibrosis was established. The comparability of ultrasound elastography of the liver with the results of puncture biopsy, in young women, increases with the progression of liver fibrosis, and can be used to determine its degree.

RELATIONSHIP BETWEEN HS-CRP AND ACUTE ISCHEMIC STROKE EVENT IN A SAMPLE POPULATION IN RAJASTHAN

Use of serum markers has been a established practice in medicine. CRP levels have been known to provide a estimate of inflammation. The present study was formulated to ascertain if levels of CRP in acute ischaemic stroke cases can be a prognostic or diagnostic marker for the condition. The study was a prospective case control format and utilized a subject pool of 50 subjects as case and control each. The study observed a significantly elevated level of CRP in cases with an acute ischaemic stroke. The study concluded that use of CRP can be a an effective modality in clinical practice in managing such cases. Keywords: CRP, Acute Ischaemic Stroke, TOAST

L-Carnitine Reduces Myocardial Oxidative Stress and Alleviates Myocardial Ischemia-Reperfusion Injury by Activating Nuclear Transcription-Related Factor 2 (Nrf2)/Heme Oxygenase-1 (HO-1) Signaling Pathway.

BackgroundMyocardial ischemia-reperfusion injury (IRI) is an important injury mechanism of myocardial infarction. The purpose of this study was to explore the effects of L-carnitine (LC) on myocardial IRI and its mechanism.Material/MethodsThe IRI model was made by ligating the left anterior descending coronary artery. Then, we injected LC intraperitoneally into the rats of the experimental group to assess the effect of LC on IRI rats by use of serum markers, Western blot, and qRT-PCR. H9c2 cells were cultured and then treated with hypoxia-reoxygenation. The effect of LC on oxidative stress, apoptosis, and nuclear transcription-related factor 2/heme oxygenase-1 (Nrf2/HO-1) signaling pathway of H9c2 cells were detected by Western blot, RT-PCR, and flow cytometry.ResultsLC significantly reduced malondialdehyde (MDA), creatine kinase (CK), and lactate dehydrogenase (LDH) levels in rat myocardial tissue and increased superoxide dismutase (SOD) expression. LC also increased the expression of SOD1/2 and Bcl-2 in rat myocardial tissue and H9c2 cells and decreased the expression of caspase3/8 and Bax. In addition, LC increased the expression of Nrf2/HO-1 signaling pathway-related molecules in H9c2 cells and increased the activity of the Nrf2/HO-1 signaling pathway. Moreover, inhibition of the Nrf2/HO-1 signaling pathway attenuated the protective effect of LC on H9c2 cells.ConclusionsLC can activate the Nrf2/HO-1 signaling pathway and reduce oxidative stress and apoptosis in cardiomyocytes, thereby reducing myocardial IRI.

Diagnosis and treatment of microvascular invasion in hepatocellular carcinoma

Microvascular invasion (MVI) is currently only confirmed by histopathological studies of surgical specimens. Preoperative diagnosis of MVI combined with clinical treatment is still a research problem and direction in hepatocellular carcinoma (HCC). How to assess the presence of MVI early and give appropriate treatment has become a research hotspot. This review focuses on recent advances in MVI-related research, including the use of serum markers, tumor tissue markers, and new imaging techniques to predict MVI, as well as the molecular biology mechanisms and therapeutic advances in MVI. The emergence of MVI may be caused by the interaction of many complex biological processes and various pathogenic factors. We need to try to select several risk factors and establish a systematic evaluation method to solve their respective deficiencies, so as to provide more practical applications for the preoperative prediction of MVI program. Simultaneously, the preoperative, intraoperative, and postoperative comprehensive treatment strategies for MVI are particularly important. The presence of MVI is thought to reflect increased capacity for local infiltration and distant metastases and affects the prognosis of HCC patients. To accurately assess MVI early based on some biomarkers prior to surgery, we need to work hard to explore and integrate various treatments to create a personalized treatment plan for MVI.

Evaluating neutrophil/lymphocyte ratio as a predictor of 30-day high-grade complications following renal surgery.

659 Background: Radical nephrectomy (RN) and partial nephrectomy (PN) for patients with renal cortical masses may carry significant risk for postoperative complications. We analyzed patient demographics and serum laboratories and morphometric measures to determine predictors of 30-day complications following RN and PN. Methods: Single institution retrospective analysis of RNs and PNs between 7/2008-4/2017. Demographic and clinical characteristics, serum laboratories, and RENAL nephrometry score were recorded. 30-day complications were graded according to the modified Clavien classification system. Primary purpose was to identify predictive factors associated with 30-day complications overall. Secondary purposes included identification of predictive factors high-grade complications (HGC; Clavien ≥3) overall and in the PN group. Factors were screened with logistic regression analysis. Results: 814 patients were analyzed (460 PN, 354 RN). 190 (23%) patients experienced 30-day complications, 107/460 (23%) PN and 83/354 (24%) RN (p = 0.951). Albumin level ≤3.5 mg/dL was predictive of overall complications (OR = 4.803, p = .008), while minimally invasive surgery (MIS) was negatively associated (OR 0.444, p < .001). Overall, 76 (9.3%) HGCs occurred, 52/460 (11%) in PN and 24/354 (6.8%) in RN (p = .028). Preoperative Neutrophil-Lymphocyte Ratio (NLR) of ≥2.78 (OR 3.216, p = .016) was a predictor of HGCs overall. MIS was negatively associated with HGCs (OR 0.444, p > .001). In the PN group only MIS was negatively associated with overall complications (OR 0.323, p < .001) and HGCs (OR 0.259, p < .001). Conclusions: While decreased serum albumin was predictive of overall complications in patients undergoing PN and RN, elevated preoperative NLR is a novel predictor for HGC. Use of serum markers may be incorporated in preoperative risk stratification counseling and nomograms.

Serum Monocyte Chemoattractant Protein-1 Predicts Liver Inflammation of Patients with Chronic Hepatitis B.

The usefulness of serum markers for predicting liver necroinflammation is limited in chronic hepatitis B (CHB) patients with normal or slightly elevated alanine aminotransferase (ALT). Monocyte chemoattractant protein-1 (MCP-1) is an important inflammatory mediator in liver disease. Our study was to investigate the expression of MCP-1 and its diagnostic value in patients with HBV-related liver necroinflammation. One hundred and six patients with hepatitis B virus (HBV) infection were recruited. All were positive for hepatitis B e antigen (HBeAg) and underwent liver biopsy. Significant inflammation was defined as inflammatory grade ≥ 2 according to Scheuer's classification scoring system. Enzyme-linked immunosorbent assay (ELISA) was used to detect expression of MCP-1 in the peripheral blood of all patients, and receiver operating characteristics (ROC) analysis was used to evaluate diagnostic accuracy of MCP-1 and liver inflammation. MCP-1 level in patients with HBV infection was higher than in healthy controls (p < 0.05). Moreover, MCP-1 level in the ALT ≥ two times of upper limits of normal (2 ULN) group was higher than that of the ALT < 2 ULN group (p < 0.05). In the ALT < 2 ULN group, the MCP-1 level in patients whose inflammatory activity was grade ≥ 2 was higher than in patients with grade < 2 (p < 0.05). ROC curve analysis showed that the area under the curve of MCP-1 in diagnosis of liver inflammation was 0.842. MCP-1 could be used as a serological marker for non-invasive evaluation of liver inflammation in CHB patients with normal or slightly elevated ALT.

A discussion of the methods for the assessment of chronic hepatitis B-related liver fibrosis regression

Antiviral therapy could reverse hepatitis B-related liver fibrosis and early-stage cirrhosis. However, the assessment of fibrosis regression remains controversial. As the gold standard for assessment, liver biopsy has its own limitations. In terms of non-invasive assessment, there are many interfering factors for transient elastography and less clinical evidence for the use of serum markers. Therefore, further evidence from clinical studies is still needed to determine the role of non-invasive methods in evaluating fibrosis regression.

Effective Prevention of Liver Fibrosis by Liver-targeted Hydrodynamic Gene Delivery of Matrix Metalloproteinase-13 in a Rat Liver Fibrosis Model.

Liver fibrosis is the final stage of liver diseases that lead to liver failure and cancer. While various diagnostic methods, including the use of serum marker, have been established, no standard therapy has been developed. The objective of this study was to assess the approach of overexpressing matrix metalloproteinase-13 gene (MMP13) in rat liver to prevent liver fibrosis progression. A rat liver fibrosis model was established by ligating the bile duct, followed by liver-targeted hydrodynamic gene delivery of a MMP13 expression vector, containing a CAG promoter-MMP13-IRES-tdTomato-polyA cassette. After 14 days, the serum level of MMP13 peaked at 71.7 pg/ml in MMP13-treated group, whereas the nontreated group only showed a level of ~5 pg/ml (P < 0.001). These levels were sustained for the next 60 days. The statistically lower level of the hyaluronic acids in treated group versus the nontreated group (P < 0.05) reveals the therapeutic effect of MMP13 overexpression. Quantitative analysis of tissue stained with sirius red showed a statistically larger volume of fibrotic tissue in the nontreated group compared to that of MMP13-treated rats (P < 0.05). These results suggest that the liver-targeted hydrodynamic delivery of MMP13 gene could be effective in the prevention of liver fibrosis.

Diagnostic Performance of Low-Dose Computed Tomography Screening for Lung Cancer over Five Years

Low-dose computed tomography (LD-CT) screening can reduce lung cancer mortality; however, it is essential to improve nodule management protocols. We analyze the performance of the diagnostic protocol of the Continuous Observation of SMOking Subjects single-center screening study, after long-term follow-up. Between 2004 and 2005, 5203 asymptomatic high-risk individuals (≥20 pack-years, aged 50 years or older) were enrolled to undergo annual LD-CT for 5 years. Nodules 5 mm or smaller underwent repeat LD-CT a year later. Nodules larger than 5.0 mm and 8.0 mm or smaller received LD-CT 3 to 6 months later. Nodules larger than 8.0 mm or growing underwent CT-positron emission tomography. True positives were any stage prevalent lung cancer, progressing nodules diagnosed at stage 1, localized multifocal cancer, or new nodules diagnosed at any stage. False negatives were progressing nodules diagnosed at stage >1. False positives were benign nodules resected surgically. Compliance was 79% over 5 years; 175 primary lung cancers were detected (0.76% per year), 136 (77.7%) were N0M0 and three were interval cancers. Eleven second primary lung cancers were diagnosed. Resectability was 87.4%; postoperative mortality 0.6%. Recall was 6.4% overall, 10.1% at baseline. False negatives were 14 of 175 (8%). Protocol sensitivity was 158 of 175 (90%); specificity 4994 of 5028 (99.4%); positive predictive value was 158 of 187 (84.5%); and negative predictive value was 4994 of 5016 (99.7%). Twenty-nine of 204 (14.2%) benign lesions were diagnosed surgically. Five-year overall and cancer-specific survival were 78% (95% confidence interval, 72-84) and 82% (95% confidence interval, 76%-88%) respectively. The performance of the CT protocol was satisfactory with an acceptable number of benign lesions biopsied surgically, low recall rate, and good oncological outcomes. However, interval and advanced cancers, and misdiagnoses, need to be reduced, perhaps by risk modeling and use of serum markers.

Diagnosis of Periprosthetic Joint Infection in Medicare Patients: Multicriteria Decision Analysis

In the setting of finite healthcare resources, developing cost-efficient strategies for periprosthetic joint infection (PJI) diagnosis is paramount. The current levels of knowledge allow for PJI diagnostic recommendations based on scientific evidence but do not consider the benefits, opportunities, costs, and risks of the different diagnostic alternatives. We determined the best diagnostic strategy for knee and hip PJI in the ambulatory setting for Medicare patients, utilizing benefits, opportunities, costs, and risks evaluation through multicriteria decision analysis (MCDA). The PJI diagnostic definition supported by the Musculoskeletal Infection Society was employed for the MCDA. Using a preclinical model, we evaluated three diagnostic strategies that can be conducted in a Medicare patient seen in the outpatient clinical setting complaining of a painful TKA or THA. Strategies were (1) screening with serum markers (erythrocyte sedimentation rate [ESR]/C-reactive protein [CRP]) followed by arthrocentesis in positive cases, (2) immediate arthrocentesis, and (3) serum markers requested simultaneously with arthrocentesis. MCDA was conducted through the analytic hierarchy process, comparing the diagnostic strategies in terms of benefits, opportunities, costs, and risks. Strategy 1 was the best alternative to diagnose knee PJI among Medicare patients (normalized value: 0.490), followed by Strategy 3 (normalized value: 0.403) and then Strategy 2 (normalized value: 0.106). The same ranking of alternatives was observed for the hip PJI model (normalized value: 0.487, 0.405, and 0.107, respectively). The sensitivity analysis found this sequence to be robust with respect to benefits, opportunities, and risks. However, if during the decision-making process, cost savings was given a priority of higher than 54%, the ranking for the preferred diagnostic strategy changed. After considering the benefits, opportunities, costs, and risks of the different available alternatives, our preclinical model supports the American Academy of Orthopaedic Surgeons recommendations regarding the use of serum markers (ESR/CRP) before arthrocentesis as the best diagnostic strategy for PJI among Medicare patients. Level II, economic and decision analysis. See Instructions to Authors for a complete description of levels of evidence.

Діагностична значимість сироваткових маркерів фіброзу печінки у хворих на HCV-інфекцію

У роботі розглядаються діагностичні можливості використання сироваткових маркерів фіброзу печінки у хворих на хронічну HCV-інфекцію. Проведення спеціальних тестів (AAR, APRI, Forns’ score, FibroIndex, FIB-4, MDA, GUCI, SHASTA, k ЛН, k ММР-1 та k ЛН/ММР-1) із використанням прямих та непрямих маркерів фіброзу печінки є альтернативним неінвазивним, доступним методом діагностики фіброзу печінки.

Use of serum markers in prediction of survival in the trapeze factorial trial evaluating docetaxel with zoledronic acid, strontium-89, or both in castrate-refractory prostate cancer (CRPC) metastatic to bone.

5057 Background: There is emerging interest in the use of bone turnover markers in CRPC to compliment current modalities and aid therapeutic management decisions. We report the preliminary results of investigation into the clinical utility of P1NP, total alkaline phosphatase (ALP) and PSA as parameters of survival in a representative sample of patients from TRAPEZE. Methods: Baseline and post treatment (cycle six or end of treatment if sooner) samples were taken from 120 patients equally distributed across the trial arms of TRAPEZE. Absolute and percentage change in the markers were investigated in relation to overall survival (OS) using the Cox Regression model. Results: Of the 120 patients, 38(32%) failed to complete 6 cycles. No relationship was observed between P1NP and OS using either absolute or percentage change (p=0.59, p=0.64). Absolute change in log PSA was significantly related to OS (HR=1.22 (95%CI 1.01, 1.48), p&lt;0.05, respectively) however percentage change in log PSA did not reach statistical significance (HR=1.006 (95%CI 0.99, 1.01), p=0.095). Absolute change in ALP was found to be inversely related to OS (HR=0.999 (95%CI 0.998, 0.999), p&lt;0.001) but percentage change in ALP was not significant (p=0.89). When the PSA and ALP models were applied to the entire trial set (757 patients) the predictive value of both absolute and percentage change in log PSA remained highly significant (HR=1.23, p&lt;0.001 &amp; HR=1.01, p&lt;0.001). In addition the significance of absolute change in ALP also remained (HR=0.999, p&lt;0.05). Conclusions: Changes in P1NP were not related to OS in CRPC patients metastatic to bone. Absolute change in ALP was inversely related to OS and both absolute and percentage changes in log PSA were also related to OS in this sub-study. When applied to the entire TRAPEZE patient group all remained statistically significant. The utility of changes in ALP and PSA, as prospective markers for studies in CRPC patients metastatic to bone, merit further evaluation.

Blood-Derived Biochemical Markers and Early Clinical Trends After Severe Traumatic Brain Injury: Utility or Futility?

Traumatic brain injury (TBI) is a major public health concern worldwide, and it is often associated with a spectrum of intracranial pathology, including parenchymal or intraventricular hemorrhage, diffuse axonal injury, as well as brain injury from extra-axial hematomas. Recently some authors have investigated the utility of serum biochemical markers in TBI. The presence of serum biomarkers with a clear impact on patient’s management is already well established in cardiology (5) .I n contrast, in the diseases of the central nervous system (CNS), the usefulness of serum markers is still under debate.

Serum Markers of Intrahepatic Cholangiocarcinoma

Cholangiocarcinoma (CCA) is a relatively rare type of primary liver cancer that originates in the bile duct epithelium. It is an aggressive malignancy typified by unresponsiveness to chemotherapy and radiotherapy. Despite advances in radiologic techniques and laboratory diagnostic test, the diagnosis of CCA remains highly challenging. Development in molecular techniques has led to go into the possible use of serum markers in diagnosing of cholangiocarcinoma. This review summarizes the principal characteristics of serum markers of cholangiocarcinoma. The tumour markers used frequently such as Carbohydrate antigen 19-9 (CA 19-9), Carcinogenic Embryonic antigen (CEA), and Cancer Antigen 125 have shown sufficient sensitivity and specificity to detect and monitor CCA. In particular, the combination of these tumour markers seems to increase their efficiency in diagnosing of cholangiocarcinoma. New markers such as Soluble fragment of cytokeratin 19 (CYFRA 21-1) Mucins, Tumour Markers2-pyruvate-Kinase (TuM2-PK) and metalloproteinase-7 (MMP-7) have been recently shown to help in the diagnosis of CCA, with in some cases a prognostic value.

Serum markers of intrahepatic cholangiocarcinoma.

Cholangiocarcinoma (CCA) is a relatively rare type of primary liver cancer that originates in the bile duct epithelium. It is an aggressive malignancy typified by unresponsiveness to chemotherapy and radiotherapy. Despite advances in radiologic techniques and laboratory diagnostic test, the diagnosis of CCA remains highly challenging. Development in molecular techniques has led to go into the possible use of serum markers in diagnosing of cholangiocarcinoma. This review summarizes the principal characteristics of serum markers of cholangiocarcinoma. The tumour markers used frequently such as Carbohydrate antigen 19-9 (CA 19-9), Carcinogenic Embryonic antigen (CEA), and Cancer Antigen 125 have shown sufficient sensitivity and specificity to detect and monitor CCA. In particular, the combination of these tumour markers seems to increase their efficiency in diagnosing of cholangiocarcinoma. New markers such as Soluble fragment of cytokeratin 19 (CYFRA 21-1) Mucins, Tumour Markers2- pyruvate-Kinase (TuM2- PK) and metalloproteinase-7 (MMP-7) have been recently shown to help in the diagnosis of CCA, with in some cases a prognostic value.

Validating Serum Markers for Monitoring of Cancer

Most of the serum tumor markers available today were introduced decades ago and were applied to clinical use without rigorous evaluation of their clinical validity. Tumor markers are mainly used for monitoring the response to therapy and to facilitate earlier detection of a relapse. Many organizations have issued guidelines on the use of tumor markers, but most of the recommendations are not based on randomized prospective trials. In this issue of Clinical Chemistry , the European Group on Tumor Markers presents guidelines (MONITOR) for designing studies on the validity of tumor markers for the serial monitoring of cancer patients, with the aim of showing whether monitoring improves outcomes, compared with other routinely used methods (1). Guidelines are needed because the use of serum markers is variable and not necessarily based on evidence. The need for validating the use of tumor markers was demonstrated in the recent evaluation of cancer antigen 125 (CA125)2 measurements for monitoring patients with ovarian cancer (2). The validity of this generally accepted practice was investigated in a study that fulfilled most of the criteria in the MONITOR guidelines. Enrolled in the study were 1442 patients with ovarian cancer who had achieved complete remission with normal CA125 concentrations after undergoing platinum-based chemotherapy. Patients …

Metastatic non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Metastatic non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Effectiveness of mesothelin family proteins and osteopontin for malignant mesothelioma

Malignant mesothelioma (MM) is an aggressive tumour with poor prognosis whose early diagnosis is difficult. Mesothelin, megakaryocyte potentiating factor (MPF) and osteopontin have attracted attention as biomarkers. The aim of the present review is to provide an overview regarding these candidate biomarkers for MM, and discuss their potential role in today's clinical practice. Mesothelin and MPF have good specificity but sub-optimal sensitivity for detection of MM, being negative both in the sarcomatoid histological sub-type and in almost half of epithelioid mesothelioma, especially in the early stages. Osteopontin is a marker of the duration of asbestos exposure, but lacks specificity for mesothelioma. Several patient characteristics influence the diagnostic accuracy of biomarkers and make the establishment of the "optimal" diagnostic threshold difficult. Mesothelin and MPF have proved useful in assessing response to treatment. Combining different markers together may lead to an improvement in diagnostic accuracy, but there is still need for research in this area. Extensive validation and further research is required to improve the use of serum markers in mesothelioma management. In the near future, their application in clinical practice is probably in monitoring response to therapy, rather than in guiding diagnostic decisions and risk assessment of asbestos-exposed populations.