Superiority of CA 125 over CA 19-9 and CEA for epithelial ovarian malignancies

In this study tumor markers CA 125, CEA and CA 19-9 were evaluated to assess the best tumor marker for epithelial ovarian carcinomas in diagnosis, prognosis and management. The results indicated that CA 125 is the best and the most superior marker today for the epithelial ovarian malignancies irrespective of the histologic type. CA 125 has the highest positivity rate in mucinous tumors compared to CEA and CA 19-9. Combined assay of either CEA or CA 19-9 or both along with CA 125 did not increase diagnostic sensitivity compared to sensitivity achieved by CA 125 alone for epithelial tumors of the ovary. Serum CA 125 concentration correlated well with pretherapy, stable course and recurrence of ovarian carcinoma. CA 125 could be used effectively for diagnosis, prognosis and monitoring of the ovarian malignancies as evident from long term follow up of adenocarcinoma ovary.     

Role of heat stable fraction of alkaline phosphatase as an adjunct to ca 125 in monitoring patients of epithelial ovarian carcinoma

Heat stable fraction (HSF) of alkaline phosphatase (ALP) was evaluated as an adjunct to CA 125 as a tumour marker for epithelial ovarian cancer in a follow-up study. In our study group 63.4% of patients had elevated HSF levels (≥10U/L) and 93.3% had elevated CA 125 levels (>35U/mL). The sensitivity of CA 125 and HSF was 93.3% and 63.3% respectively. The decline in the activity of HSF, over the pre-op levels was highly significant after the first (p=0.001) chemotherapy cycle and significant after the second and third cycles (p<0.029). Thereafter, HSF activity was almost undetectable. The decrease in CA 125 levels over the pre-op levels was significant after the first, second, third (p<0.001) and fourth (p<0.034) chemotherapy cycle. HSF can be used alone or as an adjunct to CA 125 in screening and monitoring patients of ovarian carcinoma especially in remote areas where sophisticated facilities are not available and in patients in which CA 125 levels are not raised preoperatively.     

Application of tumor markers in ovarian malignancies

Ovarian cancer is the fifth leading cause of death in women. The incidence of this malignancy increases in women over the age of 40. The overall five years survival is less than 30%, as most women present with advanced stage disease. Until recently, detection of early stage ovarian cancer has been difficult since it is usually nonpalpable and asymptomatic. The definitive diagnosis of an ovarian mass is a common problem in gynecologic patients with adnexal mass. The routine standard evaluation for adnexal masses includes patient's history, physical examination, ultrasound and histopathological examination. These parameters individually or in combination have little predictive value. The accuracy of diagnostic tools are of immense value and great concern to practicsing Gynecologists and Oncologists. The clinical application of serum concentration of CA 125, AFP and hCG is of great help not only as diagnostic aid but also in monitoring efficacy of any treatment modality like chemotherapy, radiotherapy or surgical resection. Additionally, evaluation of tumor marker concentration helps in predicting early biochemical recurrence and in prognostication in different types of ovarian malignancies. The ability to differentiate a malignant mass from a benign pelvic mass pretherapeutically could be enhanced optimally by additional use of tumor markers such as cancer antigen CA-125, alphafetoprotein and human chorionic gonadotrophin in pre-and postmenopausal women.     

Early detection of prostate cancer: evaluating the diagnostic performance of prostate specific antigen by comparing with histological technique among africans

This study was conducted to investigate the diagnostic performance characteristics of prostate specific antigen (PSA) by comparing serum PSA value with histological findings in patients suspevted of having prostate cancer in Aminu Kano Teaching Hospital. Nigeria. Clinical and Laboratory records were examined and collated for serum PSA values, together with histological findings of biopsy specimen, clinical diagnosis, age of patients, and mode of presentation. The serum PSA values were determined by ELECSYS 1010 autoanalysers Roche, Germany based on electrochemiluminescence immunoassay technique. The results show that serum PSA values increase with age in the assymptomatic non-cancer patients who came for medical check up but were within normal limit. In prostatic disease conditions PSA values were raised in benign prostatic hyperplasia 35.957± 4.0315ng/ml, in undifferentiated carcinoma 56.22±4.295ng/ml and adenocarcinoma >100ng/ml as compared to the normal range (0–4ng/ml). These cases were confirmed by histological diagnosis. It is concluded that PSA evaluations is a sensitive marker for prostate cancer but because of various other conditions that affect serum PSA concentration, other methods of investigations such as Digital Rectal examination, Trans Urethral Ultra-Sonography and histological examination should be combined to confirm diagnosis. Prognosis of patients will be better if early diagnosis is made.     

Racial and ethnic variation of PSA in global population: Age specific reference intervals for serum prostate specific antigen in healthy South Indian males

The serum PSA is universally accepted as the useful and clinically relevant tumor marker for monitoring therapy and identifying early recurrence in patients of carcinoma prostate throughout the world. However, application of serum PSA is limited to screening for early adenocarcinoma prostate among males above fifty years of age. Serum PSA concentration varies from one population to another in different parts of the world. Many groups of workers have selected 4 ng/ml of serum PSA as upper limit of normal range without giving due consideration for age specific increase in serum PSA. There is no single report available on normal decade wise age specific reference intervals for serum PSA in Indian males. The present study is undertaken to establish age specific reference intervals in healthy Indian males from 20–89 years belonging to subpopulation of Andhra Pradesh from South India. Our results revealed lowest concentration of 95 percentile serum PSA in Indian males compared to other populations globally. Contrary to this, healthy Afro Americans were found to have highest concentration of serum PSA compared to all other populations.     

TPSTM a circulating tumor marker in breast cancer

Tissue polypeptide specific antigen (TPS) measures an antigenic determinant associated with human cytokeratin 18. TPS is a marker of tumor cell activity in contrast to markers related to tumor burden. The value of detecting circulating TPS lies in the early detection of recurrence by serial determinations and in the rapid assessment of the efficacy of the treatment. Pretreatment levels of TPS in patients with metastatic breast cancer are related with prognosis. Decreasing TPS levels during therapy monitoring indicate response and a fast response is correlated to favourable prognosis. Increasing TPS levels, in the presence of clinically stable disease or partial remission, predict disease progression with a considerable lead-time. Improved effectiveness in breast cancer management can be seen when TPS is used in combination with CA 15-3. When tumor marker determinations are applied in a proper way in the appropriate situation, the results can assist the oncologist. Thus monitoring of therapy in patients with metastatic breast cancer should be based upon serial TPS and CA 15-3 determinations in serum. The use of tumor marker determinations in the early follow-up interval following surgery to detect early tumor recurrence may be simpler, more sensitive and less expensive than imaging methods.     

Tissue polypeptide specific antigen in the post therapeutic evaluation of patients with ovarian and colorectal cancer

The study was designed to evaluate the significance of tissue polypeptide specific antigen (TPS) in patients with histologically proven ovarian and colorectal cancer following treatment along with CA125 (in ovarian cancer) and CEA (in colorectal cancer). Patients were grouped as follows:

Unusually high serum CA19.9 in gastric carcinoma: A case report

We describe a case of poorly differentiated adenocarcinoma of stomach, which did not present typical symptoms of gastrointestinal malignancy on first visit. The patient, a 62 year old smoker presented with shortness of breathe and pain in right lumbar region with no history of fever. Bone scans revealed multiple hot spots in skull, sternum, lumbar vertebrae and both iliac crests. A series of tumor markers were ordered which include PSA, CEA, CA19.9, CA 72.4 and AFP. Serum PSA and AFP concentrations were within normal range. Serum CEA and CA 72.4 were raised significantly. Markedly elevated levels of serum CA19.9 were found (>45000 U/ml) in this patient. CT chest and bronchoscopic examination ruled out the possibility of cancer lung. Upper GI tract endoscopy was done to find out lesion in GI tract. An ulcerative lesion was found in lesser curvature of stomach. Histopathological examination of endoscopic biopsy revealed a poorly differentiated adenocarcinoma of stomach. An unusually high serum CA19.9 (>45000U/ml) in case of gastric carcinoma has not been reported earlier.     

Prostate specific antigen in patients of benign prostate hypertrophy and carcinoma prostate

Prostate Specific Antigen (PSA) has emerged as the most applicable and important tumor marker for carcinoma prostate. In the present study PSA was determined in serum of healthy subjects, patients of benign prostate hypertrophy (BPH) and Carcinoma Prostate (Ca−P) to evaluate its diagnostic efficiency in day to day management of prostate cancer patients and in differentiating patients of early prostate cancer from those with BPH. Receiver operating characteristic curve (ROC) revealed 2 ng/ml and 10 ng/ml cut off serum PSA level for BPH and untreated carcinoma prostate patients (Ca−P). An extremely significant increase (P<0.0001) was observed in mean PSA concentration in BPH patients and adenocarcinoma prostate patients when compared to healthy males. Clinical relevance of PSA was highlighted by a case study of cancer patient prior to any therapy till death.     

Assessment of oxidative stress and effect of antioxidant supplementation during radiotherapy in carcinoma of upper digestive tract

Oxidative stress was studied by estimating plasma levels of malondialdehyde (MDA), beta carotene, vitamin E and erythrocytic superoxide dismutase(E-SOD) activity in 50 cases of carcinoma of upper digestive tract which included carcinoma of oral cavity, pharynx and oesophagus. While plasma MDA level was found to be increased (3.5±1.0 nmole/ml), a significant decrease in beta carotene (81.2±14.5mg%), vitamin E (8.5±1.1 mg/L) level and E-SOD activity (657.0±80.6 U/G Hb) were observed in carcinoma of upper digestive tract. Patients were treated with radiotherapy which itself was toxic enough and produced its deleterious effects by generation of reactive oxygen species (ROS). As antioxdiants can detoxify ROS, beneficial effect if any, of antioxidant administration during radiotherapy was studied in two groups of patients, group A (n=5, supplemented with antioxidants) and group B (n=5, without antioxidant supplementation). Plasma MDA level was found to be elevated in both the groups but the increase in group B was significant, compared to pretreatment level. Further, body weight was found to be significantly decreased in group B patients, which was maintained in group A patients. Moreover, group A patients showed significant elevation in beta carotene concentration, thus showing beneficial effect of administration of antioxidants during radiotherapy without disturbing the desirable therapeutic effect of radiotherapy.     

Serum and platelet sialic acid in acute myocardial infarction

Blood samples from 39 patients with acute myocardial infarction and 15 healthy controls were analysed for serum and platelet sialic acid. Serum sialic acid levels in patients with acute myocardial infarction were significantly higher than controls (mean 2.7±0.46 μmol/ml Vs. 1.91±0.17 μmol/ml respectively). Levels of serum orosomucoid, an acute phase reactant, containing sialic acid, were also higher in these patients, suggesting a possible non-specific mechanism of increase in serum sialic acid concentration. In contrast, platelets contained significantly less sialic acid in patients with acute myocardial infarction than control (26.73±1.57 nmol/mg protein and 31.97±2.68 nmol/mg protein respectively).     

Diagnostic Role of Tumour Markers CEA, CA15-3, CA19-9 and CA125 in Lung Cancer

The aim of this study was to assess the diagnostic yield of the tumour markers carcinoembryonic antigen, carbohydrate antigen 15-3, carbohydrate antigen 19-9 and carbohydrate antigen 125, in serum and bronchoalveolar lavage fluid in a group of patients with bronchogenic carcinoma. Serum and bronchoalveolar lavage fluid samples were collected in a group of 90 patients with benign or malignant pulmonary diseases. After appropriate processing, tumour markers were determined by enzyme immunoassay. The diagnostic yields (sensitivity, specificity and predictive values) in each environment (serum and bronchoalveolar lavage fluid) were obtained by using "Receivers operating characteristic" curve. Determined individually, carcinoembryonic antigen, carbohydrate antigen 19-9 and carbohydrate antigen 125, showed the greatest diagnostic accuracy in bronchoalveolar lavage fluid. Carbohydrate antigen 15-3 did so in serum. Carcinoembryonic antigen was the most relevant marker in bronchoalveolar lavage fluid. For the factors evaluated in this study, determination of carcinoembryonic antigen, carbohydrate antigen 19-9 and carbohydrate antigen 125 in bronchoalveolar lavage fluid were clinically more useful markers in comparison with serum, although the latter may also be helpful in certain situations. Although there is no specific tumour marker for lung cancer, the combination of several can be used to diagnose most patients with lung cancer and also to rule out false positive and negative cases.     

Association of Prooxidant–Antioxidant Balance with Clinical and Laboratory Parameters and Its Relation to Different Drug Regimens in Polycystic Ovary Syndrome Women with Normal BMI

Polycystic ovarian syndrome is one of the most common hormonally leading cause infertility disorders. The effect of oxidant-antioxidant imbalance on disease progression has been studied in many disorders. The present study was aimed to evaluate prooxidant–antioxidant balance (PAB) in patients with polycystic ovarian syndrome compared to healthy subjects. We also studied the possible effect of treatment with available drugs on serum PAB. In this case–control study 100 polycystic ovary syndrome (PCOS) patients and 100 healthy individuals were enrolled in the study. The laboratory features of patients and controls like as serum LH and FSH concentration and hematological examinations were collected. PAB was evaluated by a colorimetric method. Serum PAB value was significantly higher before treatment compared to after treatment and healthy subjects. PAB values were also higher in subjects with irregular menstrual cycle compared to normal subjects. Our results represented that serum PAB values has an indirect significant correlation with serum LH concentration. We also found that drugs regimen containing spironolactone effectively reduced the serum PAB values. Our results showed that PCOS patients had increased level of PAB and treatment with spironolactone mainly decreases the level of serum PAB. Our results indicate that the measurements of PAB may be used as a potential laboratory marker for assessment of PCOS patients.     

Serum Paraoxonase (PON1) Activity in North-West Indian Punjabi’s with Acute Myocardial Infarction

Human serum paraoxonase-1 (PON1), an enzyme on HDL prevents oxidation of LDL thereby preventing the development of atherosclerosis. Studies done so far have lead to conflicting results. As studies are lacking in North-West Indian Punjabi’s, a distinct ethnic group with high incidence of coronary artery disease, we determined PONase activity in this population. It has been postulated that sudden lowering of serum PONase may lead to precipitation of acute myocardial infarction. We determined serum PONase activity and lipids in 100 patients each of AMI (within 24 h of onset), stable CAD and 100 age and sex matched healthy controls. These were again determined after 6 weeks in AMI patients. The mean serum PONase activity was lowest in AMI patients (23.26 U/ml) followed by stable CAD patients (102.0 U/ml) where as in controls was highest (179.8 U/ml). In patients with AMI, activity was significantly higher at 6 weeks as compared to that after acute event (49.39 %; p < 0.05). Sudden lowering of serum PONase activity in a population which already has lower activity may be one of the risk factors for development of AMI.     

Serum Biomarker Based Algorithms in Diagnosis of Ovarian Cancer: A Review

Epithelial ovarian cancer accounts for more than 90% of ovarian tumours and continues as a leading cause of death from gynaecological malignancies. It is often difficult to differentiate a benign ovarian mass from malignant ones. Invasive histopathological biopsy is used as the gold standard diagnostic tool to diagnose cancer in patients with ovarian mass. A wide spectrum of Biomarkers were tried in various studies to develop a non invasive diagnostic tool, out of which HE4 and CA 125 remain the only clinically useful biomarker. Consequently various Biomarker based algorithms i.e. Risk of Malignancy Index, risk of ovarian cancer algorithm, OVA1, risk of malignancy algorithm were generated that have been developed to assess the risk of a mass being malignant. These algorithms help in timely triage of patients. Recently in 2016 FDA cleared Ova1 test (OVERA) with CA 125-II, HE4, apolipoprotein A-1, FSH, and transferring (Sensitivity 91% and Specificity 69%) as a referral or Triage test in patients presenting with ovarian mass. Combination of protein and circulating Micro RNA analysis in blood, could provide a comprehensive screening and diagnostic panel, in management of patients presenting with ovarian mass in one clinical setting.     

Role of Brain Biomarker in Predicting Clinical Outcome in Hypertensive Cerebrovascular Ischemic Stroke

This study was undertaken to evaluate the role of serum neuron specific enolase (NSE) in prediction of disability and neurological worsening in hypertensive ischemic cerebrovascular stroke. 80 hypertensive ischemic stroke patients diagnosed by a neurologist as per WHO definition along with radiological findings suggestive of cerebrovascular stroke and differentiating from hemorrhagic stroke and 60 controls having essential hypertension coming to hospital because of regular checkup or headache but with no neurological disease were included in the study. Neurological disability was assessed by NIHSS at the time of admission (within 72 h from the onset of stroke) and on 7th day after admission and cases were categorized into mild, moderate and severe disability. Venous blood samples were drawn within 72 h from the onset of symptoms. The samples were processed as per the laboratory protocol. The serum NSE samples were analyzed using an enzyme immunoassay based on the sandwich technique. We observed raised serum NSE in hypertensive ischemic stroke (17.4 ± 5.4 ng/ml) with significant association between different hypertensive groups than in hypertensive controls (9.1 ± 0.75 ng/ml). Greater degree of disability was observed in hypertensive stroke patients with raised serum NSE and hypertensive patients with mean serum NSE level of 22.9 ± 3.6 ng/ml and dyslipidemia had greater probability of neurological worsening as compared to those with mean serum NSE level of 12.7 ± 1.2 ng/ml. Serum NSE levels can serve as a peripheral indicator of neuronal damage and assist in the prediction of disability and clinical outcome in hypertensive cerebrovascular ischemic stroke patients.     

Serum lipids in hypothyroidism: Our experience

In order to determine whether the screening of lipid profile is justified in patients with hypothyroidism we estimated serum lipids in cases having different levels of serum TSH. 60 patients of hypothyroidism in the age group of 20 to 60 yrs were studied for thyroid profile over a period of one year. On the basis of serum TSH level the cases were divided into three groups: In the first group TSH concentration was 8.8±2.99 μlU/ml, 95% confidence interval (Cl) 8.8±1.07, whereas serum total cholesterol and LDL-chol levels were 196±37.22 and 126±29.17 mg/dl respectively. The statistical analysis of these two groups showed a significant correlation between raised TSH levels and serum total cholesterol and LDL-chol (P<0.05 & P<0.01) respectively. We conclude that hypothyrodism is associated with changes in lipid profile.     

Evaluation of A60 antibodies in pulmonary and neurotuberculosis

Humoral immune response against PPD derived A60 antigen was evaluated by quantification of serum A60 antibodies in thrity healthy adults not exposed to tuberculosis (Group 1), in twenty seven healthy adults exposed to tuberculosis patients i.e. staff working in wards of tuberculosis hospital for one to thirty years (group 2), in twenty five pulmonary tuberculosis patients admitted to the Institute for Chest Diseases, Hyderabad (Group 3) and in sixty neurotuberculosis patients admitted to Neurosurgery department of our institute (Group 4). Highly significant elevation of A60 antibodies was observed in pulmonary tuberculosis patients (p<0.01) compared to healthy adult groups. A significant elevation in serum was also observed in case of neurotuberculosis group compared to both healthy groups (p<0.01). A test on A60 antibodies in serum gavv a sensitivity of 100%, specificity of 96.6%, positive predictive value of 81% and negative predictive value of 100% for pulmonary tuberculosis, whereas a sensitivity of 58%, positive predictive value of 79% and negative predictive value of 75% were noted for neurotuberculosis patients. Results of A60 antibodies in ten cerebrospinal fluids (CSF) obtained from non tuberculosis patients and thirty two CSF from patients of neurotuberculosis did not show significant elevation of antibodies. However the ninetyfive percentile value of CSF A60 antibodies was higher in neurotuberculosis (7.4 U/ml) group compared to nontuberculous group (3.8 U/ml) and the test showed a good positive predictive value (83%), very low negative predictive value (25%) and low sensitivity (63%). Serum A60 antibody assay appears to be a good serological marker available today for pulmonary tuberculosis and a supportive marker for neurotuberculosis.     

Serum adenosine deaminase in carcinoma breast

Serum Adenosine Deaminase (ADA) activity was studied in 20 control cases and 32 patients with carcinoma breast. In control group the ADA activity ranged from 13–94 IU/L with a mean of 43.75±21.55 IU/L while in patients of carcinoma breast it was 16–95 IU/L with a mean of 47.46±22.54 IU/L, but these values were not statistically different. The ADA activity was also compared with other parameters in patients of carcinoma breast but the difference was not statistically significant in the various parameters like duration of disease, menopausal status, tumor size, hemoglobin level, total leucocyte count, absolute lymphocyte count, total serum proteins, serum albumin, histological grade of tumor and lymphocytic infiltration. The only significant difference in ADA activity was when N1 status of lymph node was compared with N2 status of lymph node.     

Usefulness of ferroxidase activity of ceruloplasmin in the diagnosis of Wilson’s disease

Serum ceruloplasmin is one of the most commonly used screening tests for Wilson’s disease. However immunological assays for ceruloplasmin are not recommended for diagnosis and management of Wilson’s disease through calculation of free copper index. Enzymatic methods using non-physiological substrates have toxicity and stability problems, making them difficult to automate. Ferroxidase assays may be a satisfactory alternative for measuring serum ceruloplasmin. The o-dianisidine hydrochloride manual method for estimation of serum ceruloplasmin enzyme activity was compared with an automated method using the ferroxidase activity of ceruloplasmin in measurement in a double blind study in 91 consecutive patients screened for Wilson’s disease. The o-dianisidine and ferroxidase methods both successfully identified 7 patients with Wilson’s disease. Values for these 7 patients in the o-dianisidine and ferroxidase methods were median 5.0 (range 0–16.0 U/L) and median 45.0 (range 4–166 U/L) respectively. There were 7 other positive values (<62 U/L) with the o-diansidine method and 2 (<200 U/L) with the ferroxidase method, where WD was not confirmed. ROC curves for both methods showed area under the curve of 0.998 for o-dianisidine and 0.997 for ferroxidase. Using literature cut off values of 62 U/L and 200 U/L respectively both methods had 100% sensitivity and specificity was 91.7% (o-dianisidine) and 97.6% (ferroxidase). For the o-dianisidine assay, specificity was improved to 98.8% using a cut off of 22.5 U/L. In the 84 persons (46 adults and 38 children) in whom the diagnosis of Wilson’s disease was not established, the mean value for ceruloplasmin activity by the o-dianisidine and ferroxidase methods was 124.7 ± 48.7 U/L and 571.4 ± 168.1 U/L respectively. There were no significant differences between sex or age of patients (p > 0.29). In a subsequent evaluation with 372 specimens, the Pearson correlation coefficient between the assays was 0.908, p < 0.01, slope 4.06, intercept 265.8, with the manual assay as the x-axis. The ferroxidase assay is a suitable replacement for the o-dianisidine assay in detecting patients with Wilson’s disease.