Samario-153-Lexidronam (EDTMP) en el tratamiento de las metástasis óseas / Samarium-153-Lexidronam (EDTMP) for the management of bone metastases

Las metástasis óseas son una complicación frecuente en pacientes neoplásicos, en este sentido, el tejido óseo ocupa el tercer lugar de todos los órganos y sistemas con metástasis después del pulmón e hígado. Aproximadamente un 75 por ciento de los enfermos con metástasis óseas sufrirán dolor, siendo estas la causa más frecuente de dolor en pacientes con cáncer. El dolor óseo aumenta con los movimientos y a la presión, limitando la autonomía del enfermo y su calidad de vida. El tratamiento incluye varios abordajes terapéuticos complementarios entre sí, como AINE, opiáceos, bifosfonatos, radioterapia, radioisótopos, cirugía y técnicas intervencionistas. Presentamos dos casos clínicos, el primero una mujer diagnosticada de carcinoma de mama y el segundo un hombre con adenocarcinoma de próstata y carcinoma vesical, ambos casos con diseminación metastásica ósea. Ante la persistencia del dolor y la dificultad en su control fueron tratados con Samario-Lexidronam (Sm-153), Quadramet® con resultados satisfactorios. Se consiguió disminuir el dolor, también el descenso en el consumo de opiáceos a pesar de la progresión de la enfermedad. El Sm-153 es un radioisótopo emisor de radiaciones beta y gamma. Presenta una semivida física corta, una alta afinidad por el esqueleto óseo y una eliminación urinaria. El alivio del dolor es del 65-80 por ciento, el inicio de la analgesia es rápido y la duración de esta es de 8 a 12 semanas con escasos efectos secundarios (AU)

Preoperative CA-125, CA 19-9 and nuclear magnetic resonance in endometrial carcinoma: correlation with surgical stage.

Serum CA 125 and CA 19-9 determinations and nuclear magnetic resonance (NMR) of the pelvis were performed in 100 consecutive endometrial carcinoma patients, who were surgically staged afterwards. The aim was to assess the value of these combined studies to predict the surgical stage of endometrial carcinoma. The results were correlated with the final surgical stage. NMR or elevated tumor marker values alone were able to predict a surgical stage equal to or higher than IC in 84.6 and 78.8% of the cases, respectively. The combination of both procedures yielded better positive and negative predictive values (90.9 and 88%, respectively), but only when both were concordant (p < 0.0001). When only one of them suggested a higher stage (28% of the cases), the positive predictive value decreased to 70.4%. The accuracy in predicting a higher surgical stage in endometrial carcinoma by preoperative noninvasive means is slightly improved when combining NMR and serum tumor marker determinations. The predictive value, however, is not absolute and clearly unsatisfactory in 28% of the cases.

Total immunoreactive alpha-inhibin in human seminal plasma, sperm quality, and in vitro fertilization rates.

OBJECTIVE: To assess the relationship between the concentrations of total immunoreactive alpha-inhibin in human seminal plasma, sperm quality, and in vitro fertilization (IVF) rates. SETTING: Medical school hospital. DESIGN: Prospective study. PATIENTS: 72 consecutive couples undergoing IVF with husband's sperm in which at least 4 oocytes were obtained. MAIN OUTCOME MEASURES: Alpha-inhibin determination by means of enzyme-linked immunosorbent assay, sperm analysis for density and motility, IVF rates. RESULTS: Total immunoreactive alpha-inhibin levels were not correlated with IVF rates. Nor were there any differences in fertilization rates in the different groups. Lower inhibin levels were found in oligozoospermic cases. Lower sperm counts were found in cases with inhibin values below the median value, and also with respect to various other cutoffs. No correlation was found between inhibin levels and any of the sperm variables measured. CONCLUSION: Total immunoreactive alpha-inhibin is not a prognostic factor in IVF cycles. However, an association was found between inhibin and sperm concentration, suggesting that alpha-inhibin in the human seminal fluid could be a marker for some aspects of spermatogenesis.

Serum neuron-specific enolase (S-NSE) and the prognosis in small-cell lung cancer (SCLC): a combined multivariable analysis on data from nine centres.

The influence of pretreatment serum neuron-specific enolase (S-NSE) in addition to more conventional prognostic factors on survival duration in small-cell lung cancer (SCLC) was investigated in 770 patients from nine centres in six countries. The other variables included stage of disease, performance status (PS), age, sex, serum lactate dehydrogenase (S-LDH), serum alkaline phosphatase (S-AP), and serum carcinoembryonic antigen (S-CEA). Increased values of S-NSE (> 12.5 micrograms-1 l) were observed in 81% of the patients, whereas S-LDH, S-AP and S-CEA were elevated in only half of the patients or less. Multivariable analysis by Cox's proportional hazard model disclosed S-NSE as the most powerful prognostic factor followed by poor PS and extensive stage disease. If PS was ignored, S-LDH came up as a significant prognostic factor. S-AP, S-CEA, age and sex had no significant influence on the prognosis. The three prognostic factors, S-NSE, PS and stage of disease, enabled establishment of a prognostic index (PI) based on a simple algorithm PI = zNSE + z(stage) + 2zPS. This segregated the patients into four groups with clearly different prognosis. The median survival and 95% confidence intervals of the four groups were: 468 days (540-408), 362 days (405-328), 256 days (270-241) and 125 days (179-58). Based on the present results we recommend S-NSE and PS, in addition to stage, for prognostic stratification in treatment trials on SCLC.

Levels of CA-19.9, CA-125, and CA-195 in seminal plasma and in vitro fertilization rates.

OBJECTIVE: To assess the relationship between carbohydrate tumor markers in seminal plasma and fertilization rates in IVF cycles. DESIGN: Prospective study. SETTING: Academic tertiary hospital. PATIENTS: Forty-six consecutive couples subjected to IVF in which at least one oocyte was obtained. MAIN OUTCOME MEASURES: Determination of CA-19.9, CA-125, and CA-195 in seminal plasma 1 week before IVF. RESULTS: CA-125 was higher in the group without fertilization (321 +/- 198 U/mL, mean +/- SD) than in the group in which at least one oocyte was fertilized (155 +/- 165 U/mL), whereas CA-19.9 and CA-195 were similar in both groups. However, at the cutoff 66%, lower values of CA-19.9 were found in the fertilization group rate < 66% (707 +/- 1,217 versus 1,069 +/- 1,084) and of CA-195 (67 +/- 44 versus 218 +/- 274). No correlation was found between tumor marker levels and fertilization rates. CONCLUSION: CA-125 seems to be an indicator of sperm fertilization capacity, whereas the importance of CA-195 and CA-19.9 will require further studies.

Measurement of the serum tumor marker neuron-specific enolase in patients with benign pulmonary diseases.

Serum concentrations of neuron-specific enolase (NSE) were measured in 135 patients with benign pulmonary diseases who also underwent a clinical, laboratory, and radiologic evaluation. Eleven percent of the patients as a whole and 27.3% of those who were tuberculous had abnormal serum levels of NSE. Significant differences in NSE levels were observed among the six diagnostic groups evaluated (p = 0.002). Males had higher levels than females (p = 0.003), and patients infected with the human immunodeficiency virus (HIV) had higher NSE levels than those not infected (p = 0.0026). Patients with alveolar infiltrates or an interstitial pattern on chest X-ray had higher NSE levels than those with normal radiographs (p = 0.003 and p = 0.01, respectively). In fact, only 3.6% of the patients with normal radiographs had above-normal levels of NSE. Direct damage to the neural or neuroendocrine lung cells or some degree of local hypoxia is likely to play a role in the increase in NSE in these patients. The small number and degree of abnormal values of NSE observed in this study make it unlikely that an underlying benign lung disease will substantially modify the interpretation of an increased NSE value in patients with lung cancer. However, care should be taken in interpreting a moderately abnormal NSE value in the cancer patient in the presence of lung infiltrates such as obstructive pneumonitis.

Human seminal plasma analysis of five tumor markers: CA 125, alpha-fetoprotein, CA 50, CA 19.9, and CA 195.

OBJECTIVE: To evaluate tumor markers in seminal plasma and their possible relationship with fertility. METHODS: Five different tumor markers (alpha-fetoprotein, CA 125, CA 19.9, CA 50, and CA195) were studied in seminal plasma and serum from 42 males (14 volunteers from semen donation and 28 males from infertile couples). RESULTS: CA 50 and CA 19.9 levels were more than 300 times as high in seminal plasma as in serum (4,396.4 U/mL vs. 13.9 and 3,893.5 U/mL vs. 11.5). CA 125 levels were 14 times as high in seminal fluid as in serum (217.2 U/mL vs. 15.1), and CA 195 levels 22 times as high (122.5 U/mL vs. 5.6). alpha-Fetoprotein levels in seminal plasma were one-third those in serum (0.75 ng/mL vs. 2.47). Seminal levels of CA 125, CA 50, and CA 19.9 were correlated with the duration of infertility. Compared with donors, among seminal fluids from infertile couples there was a trend to higher levels of CA 19.9 and CA 125. CA 125 levels were lower in samples having normal sperm counts, and CA 125 and CA 19.9 levels were lower among couples who conceived compared with those who did not conceive. Tumor markers, either in seminal plasma or in serum, were not found to be correlated with semen characteristics. CONCLUSIONS: It appears that seminal levels of the tumor markers studied depend on more factors than the single serum concentration. The biological significance of the high seminal levels of the four carbohydrate antigens, and the association of low levels of CA 125 and CA 19.9 and fertility, could not be determined from our study. It is suggested, however, that CA 125 and CA 19.9 could be used as seminal plasma markers of fertility.

Serum laminin levels offer only a little additional information in liver disease.

We have measured serum laminin, a marker of portal hypertension, in 151 patients with nonmalignant liver diseases, to evaluate its utility in cirrhosis and portal hypertension. There were abnormal serum levels in 43.1% of the patients as a whole and in 62.7% of the cirrhotics. Laminin showed a correlation with many laboratory tests, especially those that reflect liver insufficiency and alcohol intake. Cirrhotics had higher laminin levels than noncirrhotics (p < 0.0001); an association was also found with portal hypertension (p < 0.0001), but laminin was also increased in patients without portal hypertension. Our results suggest that liver dysfunction can also lead to abnormal laminin concentrations, probably through slower metabolization rate. Laminin serum concentrations reflect the severity of the liver disease, and are also a marker of alcohol consumption. Determination of laminin serum levels could play an adjunctive role with respect to other liver tests in the evaluation of these patients although the measure does not really provide more useful information.

A clinical and biochemical study on tissue polypeptide antigen (TPA) in non-malignant hepatic disorders.

The behaviour of the tumour marker TPA was studied in 160 patients with benign diffuse liver diseases which underwent a thorough clinical and biochemical evaluation. Abnormal serum levels were found in 71.9% of the 160 patients, 87.2% of the 86 cirrhotics, and 98.4% of the 61 cirrhotics with elevated aspartate aminotransferase (ASAT) levels. TPA correlated with numerous clinical and biochemical markers of liver disease, serum ASAT being the most significant one (r = 0.63, p < 0.00001). TPA values were higher in cirrhotics than in non-cirrhotics (p < 0.0001) and in the patients with increased ASAT as compared with those with normal ASAT (p < 0.0001). In liver disease the cut-off level had to be raised five-fold to allow 10% abnormal values. This fact severely limits the usefulness of TPA in oncologic patients who also have liver disease. Cytolysis and/or liver regeneration appear to play an important role in the increase of TPA in these patients although other mechanisms such as impaired metabolism due to hepatocellular insufficiency also may be involved.

Serum concentrations of laminin in cirrhosis of the liver.

Laminin, a glycoprotein synthesised by Ito cells, has been considered a marker of fibrogenesis. The behaviour of laminin and clinical and laboratory data in 83 patients with cirrhosis were studied to find the factors associated with increases in this glycoprotein. There were increased concentrations of laminin in 62.7% of the patients (40% of the Child's A, 64.5% of the Child's B, and 75% of the Child's C categories). Significant differences in laminin concentrations were found between the Child's grades (p = 0.009) and between patients and controls (p < 0.0001). Correlations were found between laminin concentrations and mean corpuscular volume, aspartate aminotransferase, aspartate aminotransferase: alanine aminotransferase ratio, alkaline phosphatase activity, bilirubin and glycocholic acid concentrations, and hypoalbuminaemia--that is, variables related to liver insufficiency and alcohol intake. Moreover, patients with an alcohol intake higher than 100 g/day had higher laminin concentrations than those with a lower intake (p = 0.03). Conversely, there was no significant association with portal hypertension. Multivariate analysis showed that mean corpuscular volume, bilirubin concentrations, and hypoalbuminaemia were independently associated with laminin concentrations. Poor degradation associated with liver insufficiency seems to play an important part in the increase in serum laminin concentrations in these patients.

Study of serum procollagen type III peptide in patients with hepatic cirrhosis from a clinical point of view.

N-terminal procollagen-III peptide (P-III-P) has been considered a marker of fibrogenesis and inflammatory activity of the liver. We measured the P-III-P serum levels in 83 cirrhotic patients fully characterized from a clinical and laboratory point of view. Cirrhotic patients had significantly higher P-III-P serum levels than controls (P < 0.0001). Of the cirrhotic patients 73.5% had increased P-III-P. A significant negative correlation was found between P-III-P and transaminases, and patients with normal values of alanine amino-transferase had higher P-III-P serum levels than those with increased values (P = 0.03). On the other hand, no significant association was found with portal hypertension, Child classes, or alcoholic liver disease. No one independent factor appears to be responsible for the increase in P-III-P. The measurement of serum P-III-P is of little if any use in the evaluation of cirrhotic patients.

Serum levels of CA 50 in nonmalignant liver diseases: a clinical and biochemical study.

CA 50 is a tumor marker used in the evaluation and follow-up of some cancers, especially of the digestive tract. However, CA 50 frequently produces false-positive results, particularly in pancreatic and hepatobiliary diseases. This study was carried out to evaluate the behavior of CA 50 in 159 patients with benign diffuse liver diseases, who underwent a thorough clinical and laboratory evaluation. There were abnormal levels of CA 50 in 56% of the 159 patients, and in 75.3% of the 85 cirrhotics, with very high values in some cases. We found significant correlations between CA 50 and some clinical and biochemical parameters. Significantly higher levels of CA 50 were found in cirrhotics than in noncirrhotics (p < 0.0001), and in hyperbilirubinemic patients than in those with normal bilirubin (p < 0.0001). Several mechanisms, including liver dysfunction and pathological changes of the smallest bile ducts, probably are responsible for the increase in CA 50. Several cut-offs for different subsets of patients, according to the diagnosis and level of bilirubin, have been calculated. Whenever CA 50 is used in the evaluation of a cancer patient, a benign liver disease should be excluded, because the liver disorder can result in increased serum levels of CA 50, independent of cancer.

Study of the tumor marker carbohydrate antigen 50 in liver cirrhosis. Pathogenetic considerations.

Carbohydrate antigen 50 (CA 50) is a tumor marker that increases in many malignancies, especially in carcinoma of the digestive tract. False-positive results occur in benign liver disease. The behavior of CA 50 in 86 cirrhotic patients was studied, with thorough clinical and laboratory evaluations. There were abnormal values in 75.6% of the patients without significant differences among the different Child's grades. Significant correlations with some liver tests were found, especially transaminases, and at lower degrees with cholestatic parameters. Despite the previously reported relation with cholestasis, especially in biliary diseases, the CA 50 serum levels of the authors' cirrhotic patients appeared to be more closely related to cytolysis, according to the results of several statistical tests, including multivariate analysis. Because of the percentage and the levels of the abnormal results, this antigen cannot be used as a tumor marker in cirrhotic patients. Cytolysis seems to have a pathogenetic role in the increase of CA 50, at least in cirrhosis.

Evaluation of the behavior of carcinoembryonic antigen in cirrhotic patients.

Benign liver diseases are a cause of increased serum levels of CEA. We studied the behavior of CEA in 86 patients with liver cirrhosis who underwent extensive clinical and laboratory evaluation. We found abnormal CEA levels in 38.4% of the patients (28.6% Child's grade A, 40.6% Child's B, and 42.4% Child's C) with a mean of 4.75 ng/ml. Significant differences were found between patients and controls. There was a trend towards higher levels of CEA in more severe cirrhosis according to Child's classification, although this was not significant. We found significant correlations between CEA and some liver tests, including glycocholic acid (r = 0.264., p = 0.012), a marker of severity in liver diseases. The increase of CEA in these patients is probably due to alterations in its metabolic processing caused by hepatocellular dysfunction. Moderate elevations of serum CEA can be expected in cirrhotic patients independently of malignancy.

Tissue polypeptide antigen (TPA) in chronic active hepatitis and mild liver diseases.

Tissue polypeptide antigen (TPA) is a non-specific tumor marker with a broad reactivity. Increases in TPA are also observed in benign liver diseases. We conducted this study to evaluate the usefulness of TPA serum level determination in 15 patients with chronic active hepatitis (CAH) and in 30 patients with mild liver diseases (MLD) diagnosed at the time of evaluation. TPA levels were abnormal in 73.3% of CAH patients and in 40% of MLD patients. CAH patients had significantly higher TPA levels than MLD patients (p = 0.006). There was a significant correlation between TPA and ASAT (r = 0.581 p < 0.00001), suggesting that cytolysis plays an important role in the increase in TPA. A TPA value of twice the normal level will unlikely be due to MLD (specificity 90%). TPA can be used in the clinical characterization of these patients and in the selection of patients for biopsy.

CA 19-9 in non-neoplastic liver diseases. A clinical and laboratory study.

CA 19-9 is a tumor marker with frequent false-positive results in pancreatic and hepatobiliary diseases. This study was carried out to evaluate the behaviour of CA 19-9 in 159 patients with benign diffuse hepatic disease, 85 cirrhotics and 74 non-cirrhotics, who underwent a thorough clinical and laboratory evaluation. CA 19-9 was correlated with numerous clinical and biochemical features of liver diseases: bilirubin and alkaline phosphatase activity were the most reliable predictors of the CA 19-9 concentrations. There were abnormal concentrations of CA 19-9 in 34.6% of the 159 patients and in 47.1% of the 85 cirrhotics. Because of the large number of abnormal values and the high concentrations attained in some of them, the cut-off used in patients with diffuse hepatic disease needs to be set at more than twice the basal level, thus allows only 10% of false positives. Even higher values are required for cirrhotic or icteric patients. The results indicate that cholestasis plays an important role in causing the raised CA 19-9 in these patients, although there were also abnormal concentrations in normobilirubinemic patients.