Prognostic significance of bone metastases in patients with metastatic prostate cancer

BACKGROUND: The distribution of bone metastases on a bone scan has not been duly considered when assessing the prognosis of metastatic prostate cancer. METHODS: The medical records of 76 patients with newly diagnosed, untreated metastatic prostate cancer were reviewed. According to the distribution of bone metastases on the initial bone scan, we divided the patients into three groups: Group I (having bone metastases exclusively within the pelvis and the lumbar spine), Group II (having bone metastases exclusively outside these bones), and Group III (having bone metastases in both areas). RESULTS: Among the responders to androgen deprivation, those in Group I survived significantly longer than did those in Groups II or III. Because the extent of the disease and the distribution of histologic differentiation in Groups I and II were similar, the results indicate that the presence of bone metastases outside the pelvis and the lumbar spine is predictive of short survival time. This prediction was not possible when the extent of disease (EOD) grading system was used. CONCLUSION: The distribution of bone metastases on the initial bone scan should be considered as a variable for the prognostic stratification of patients with metastatic prostate cancer.     

Prognostic significance of colony-stimulating factor receptor expression in ipsilateral breast cancer recurrence

The macrophage colony-stimulating factor receptor (CSF-1R), the product of the c-fms proto-oncogene, regulates normal proliferation and differentiation of macrophages and trophoblasts. Recent research found abnormal expression of CSF-1R in human carcinomas of the breast, endometrium, and ovary. Furthermore, activation of CSF-1R by its ligand has been shown to regulate invasiveness and anchorage-independent growth in breast carcinoma cells. To study the significance of CSF-1R expression in breast cancer, we designed a case-controlled immunohistochemical study. We chose 80 patients from a database of 1200 early stage I or II breast cancer patients treated with conservative surgery and radiation therapy. Expression of CSF-1R in the tumors of 40 patients who experienced an ipsilateral breast tumor recurrence (IBTR) as a primary site of relapse were compared with 40 patients who had not experienced an IBTR. The index and control patients were matched by age, clinical stage, nodal status, and follow-up. Paraffin-embedded sections were immunostained with antibodies directed toward CSF-1R. For the CSF-1R antibody, a total of 28 index cases (70%) demonstrated strong staining, whereas only 16 control cases (40%) demonstrated high immunoreactivity (P = 0.007). The CSF-1R antibody showed a positive correlation for local relapse, but no correlation was found between CSF-1R expression and distant metastasis. In summary, our findings provide evidence for the poor prognostic role of CSF-1R in IBTR.     

Prognostic significance of cathepsins B and L in primary human breast cancer

PURPOSE: Evaluation of the clinical significance of cytosolic tumor levels of the lysosomal cysteine proteases cathepsin B (catB) and cathepsin L (catL) in patients with primary breast cancer. PATIENTS AND METHODS: CatB (n = 1,500) and catL (n = 1,391) levels were determined by enzyme-linked immunosorbent assay (ELISA) in cytosols routinely prepared from frozen-tissue samples that were submitted to our laboratory for the assessment of steroid-hormone-receptor status. The median duration of follow-up of patients still alive at the time of analysis was 93 months. RESULTS: Relating catB and catL levels with classical prognostic factors, the proteases were positively correlated with the number of positive lymph nodes (P < .01), and negatively with the level of steroid-hormone receptors (P < .01). We did not find a significant relationship between catB or catL levels with age and menopausal status of the patients or with the size of the primary tumor. The levels of catB and catL were positively correlated with each other and with the rates of relapse and death (all, P < .0001). In multivariate regression analysis for relapse-free survival (RFS) and overall survival (OS), corrected for the contribution of age/menopausal status, tumor size, the number of positive lymph nodes, and steroid-hormone-receptor status, catB and catL were significant predictors of the rates of relapse and death (all, P < .01). No statistically significant interactions of catB or catL with any of the classical prognostic factors or with each other were observed in their associations with the rates of relapse and death. CONCLUSION: CatB and catL levels measured in routinely prepared cytosols are strong parameters to predict the rate of relapse and the length of survival after treatment of the primary breast tumor.     

Prognostic factors in breast cancer

Prognostic factors are clinical and pathological features that give information in estimating the likely clinical outcome of an individual suffering from cancer. The author gives a short review of the most important prognostic factors in breast cancer. 376 breast cancer cases of a ten year interval in a county hospital are summarized. Traditional clinico-pathological parameters i.e. TNM and steroid receptor status are discussed. The more common karyotipic, oncogene and tumor suppressor gene alterations are outlined in the study. Methods for their detection are presented and their value in prognostication is reviewed. Emphasis was laid on steroid receptors, c-erpB-2, p53 and bcl-2 alterations. Genes responsible for heritable forms of increased breast cancer risk are briefly reviewed.     

Prognostic significance of febrile episodes in lung cancer patients receiving chemotherapy

AIM: To evaluate the prevalence of iron overload in chronic hepatitis C and its relationship with liver histology. PATIENTS AND METHODS: Serum iron, unsaturated iron binding capacity and ferritin levels were determined in 204 consecutive anti-hepatitis C virus positive subjects, whereas hepatic iron concentration, hepatic histological grading and staging, hepatitis C virus genotypes were further assessed in a subgroup of 50 patients who underwent liver biopsy for chronic hepatitis. RESULTS: An increase in the serum markers of iron metabolism was more frequently found in subjects with aminotransferase activities above the normal range, whereas hepatic iron overload, established by direct hepatic iron determination, was found only in 9/50 (18%) patients with chronic hepatitis C. No serum iron marker could reliably predict hepatic iron stores. Patients with mild iron overload usually showed active hepatitis and fibrosis, whereas iron overload was not present in patients without fibrosis or with very mild fibrosis. Two out of nine patients with iron overload were shown to be beta thalassaemia heterozygous, and two were heterozygous carriers of a putative haemochromatosis gene mutation (His63Asp). CONCLUSIONS: Many anti-hepatitis C virus positive patients with elevated aminotransferase activities have serum ferritin levels above the normal range, but only a minority of patients with chronic hepatitis C have a mild iron overload. In chronic hepatitis C, a relationship does exist between hepatic iron content and liver fibrosis.     

Prognostic significance of stromelysin 3, gelatinase A, and urokinase expression in breast cancer

The effects on malaria parasite growth of antisense and sense oligodeoxynucleoside phosphorothioates based on a merozoite surface protein mRNA was examined. Specific antisense effects of the oligonucleotides could not be demonstrated over three cycles of schizogony or when added as a complex with cationic liposomes. Antisense and sense oligonucleotides however, inhibit merozoite invasion of red blood cells at similar concentrations to dextran sulphate, a polyanion, as determined by microscopy and [3H]hypoxanthine incorporation into DNA. Neutralisation of the negative charge on the oligonucleotides by binding to cationic lipid liposomes, prevented the inhibition of merozoite invasion. We postulate that oligonucleotides because of their polyanionic nature interfere with the binding of merozoites to receptors on red blood cells and that polyanions may be useful in malaria therapy.     

Prognostic significance of urokinase-type plasminogen activator and plasminogen activator inhibitor-1 in primary breast cancer

The uPA-mediated pathway of plasminogen activation is central to cancer metastasis. Whether uPA and PAI-1 are related to local recurrence, metastatic spread or both is not clear. We present a retrospective study of 429 primary breast cancer patients with a median follow-up of 5.1 years, in which the levels of uPA and PAI-1 in tumour extracts were analysed by means of an enzyme-linked immunosorbent assay. The median values of uPA and PAI-1, which were used as cut-off points, were 4.5 and 11.1 ng mg(-1) protein respectively. The levels of uPA and PAI-1 were correlated with tumour size, degree of anaplasia, steroid receptor status and number of positive nodes. Patients with high content of either uPA or PAI-1 had increased risk of relapse and death. We demonstrated an independent ability of PAI-1 to predict distant metastasis (relative risk 1.7, confidence limits 1.22 and 2.46) and that neither uPA nor PAI-1 provided any information regarding local recurrence.     

Prognostic significance of microsatellite instability in patients with gastric carcinoma

A proportion of gastric adenocarcinomas exhibit replication errors manifested as microsatellite instability. The clinicopathological and prognostic significance of this abnormality remains uncertain. This study aimed to determine the importance of microsatellite instability by analysing a large series of gastric carcinomas from an English population. Using a novel fluorescent polymerase chain reaction technique, we amplified 11 microsatellite sequences from paired normal and carcinoma DNA from 101 patients who underwent a potentially curative resection for gastric carcinoma. Overall, 21% of cases demonstrated microsatellite instability in at least one locus. At least four loci were examined in each case. A replication error positive phenotype (minimum of 29% of loci affected) was detected in 9% of cases. There was no statistically significant association between the presence of microsatellite instability or replication error positive phenotype and the patient's age, sex, tumour site, stage, node status, histological subtype or grade. Carcinomas confined to the mucosa or submucosa (T1) showed a significantly higher frequency of instability and replication error positive phenotypes than T3 lesions (P = 0.03 and P = 0.05, respectively). A larger proportion of patients who were microsatellite instability or replication error positive were alive at 5 years compared with those who were negative but this did not reach statistical significance (P = 0.15 and P = 0.16, respectively). We identified a subset of gastric carcinomas from a relatively low-risk population which showed evidence of microsatellite instability. There were no statistically significant 5-year survival advantages in cases demonstrating microsatellite instability or replication error positive phenotypes. The detection of microsatellite instability is of limited prognostic value in gastric carcinoma.     

The significance of p53 autoantibodies in the serum of patients with breast cancer

Serum p53 autoantibodies were studied in 82 patients with Stage 1 or 2 breast cancer using an ELISA assay. Tissue expression of p53 in these patients was also examined. High levels of serum p53 autoantibodies were detected in 48% (39/82) patients, while 23% (19/82) were tissue positive. Patients with high serum p53 autoantibodies levels were not significantly different to those with low levels with respect to, tissue p53, tumour grade, size, stage or oestrogen receptor status. Tissue immunoreactivity for p53 was significantly associated with tumour grade and negative oestrogen receptor status. Patients in both groups were followed for a median of over five years but the presence of p53 autoantibodies in serum was not prognostic with respect to disease free interval or survival. In this study detection of p53 autoantibodies in serum does not correlate with any of the usual tumour related prognostic factors, nor does it correlate with clinical outcome.     

Prognostic significance of tumour markers in endometrial cancer

BACKGROUND: Steroid 5 alpha-reductase is implicated in the pathogenesis of benign prostatic hyperplasia (BPH). We studied the in vitro and in vivo effects of FR146687, a new inhibitor of 5 alpha-reductase. METHODS: Two isozymes of rat and human 5 alpha-reductases were expressed in 293 cells. In vivo effects of drugs were evaluated on rat and dog prostates. Castrated immature rats were injected with testosterone propionate (TP) or 5 alpha-dihydrotestosterone propionate (DHTP) to induce growth of the ventral prostates. Testosterone and 5 alpha-dihydrotestosterone (DHT) contents in rat and dog prostates were measured by gas chromatography-mass spectrophotometry (GC-MS). RESULTS: FR146687 showed noncompetitive inhibition in both isozymes and no inhibitory effects on other steroid oxidoreductases. In mature rats and castrated immature rats treated with TP, FR146687 dose-dependently reduced ventral prostate and seminal vesicle weight at doses above 0.1 mg/kg, while castrated immature rats treated with DHTP were not affected by FR146687. FR146687 showed more potent reduction of rat prostates than finasteride. DHT concentration in the prostates was significantly reduced when FR146687 was administered to rats and beagles. CONCLUSIONS: FR146687 is a dual inhibitor for 5 alpha-reductase isozymes and significantly reduced the growth and DHT content in the prostate.     

Prognostic significance of postoperative empyema in lung cancer

OBJECTIVE: To evaluate the safety and feasibility of laparoscopic choledocholithotomy via choledochotomy for the treatment of choledocholithiasis. DESIGN: A prospective series of 1332 consecutive patients who underwent laparoscopic cholecystectomies, with a mean follow-up of 21.2 months. SETTING: University-affiliated referral center. Patients: Forty-three patients (3%) with documented common bile duct stones from January 1991 to February 1995. INTERVENTIONS: Laparoscopic choledocholithotomy with choledochotomy and T tube drainage were performed in 40 patients. Postoperative endoscopic sphincterotomy after laparoscopic cholecystectomy was performed in three patients. MAIN OUTCOME MEASURES: Documented removal of common bile duct stones and procedure-related complications. RESULTS: Laparoscopic choledocholithotomy via choledochotomy was successful in 35 (88%) of 40 patients in whom this procedure was attempted. The mean (+/- SD) operation time was 191.3 +/- 75.4 minutes, and the mean (+/- SD) length of postoperative stay was 10.4 +/- 2.7 days. Seven complications (18%) were recorded, including three major complications (8%) and two retained stones (5%). CONCLUSIONS: Laparoscopic choledocholithotomy via choledochotomy can be performed safely, without increasing the morbidity rate as compared with that of open choledocholithotomy. Thus, some of the advantages of minimally invasive surgery are preserved.     

Prognostic significance of lymph node dissection in gastric cancer

The results for 162 patients who underwent curative gastrectomy for gastric cancer from January 1988 to June 1994 were analysed statistically with special reference to the effect of lymph node dissection. Median survival was 69.3 months and the overall cumulative 5-year survival rate was 50.2 (95 per cent confidence interval (c.i.) 41.6-58.1) per cent. By univariate analysis age, histology, depth of tumour invasion, node involvement, number of metastatic lymph nodes and type of lymphadenectomy were found to be significant factors related to survival time. Multivariate analysis with the Cox model and stratified for tumour node metastasis stage revealed that only the number of metastatic nodes (P = 0.04) and the extent of lymphadenectomy (P = 0.003) affected survival independently. With respect to D1 lymphadenectomy, the relative risk associated with D2 and D4 lymphadenectomy was respectively 0.61 (95 per cent c.i. 0.34-1.10) and 0.26 (95 per cent c.i. 0.12-0.60). The 5-year survival rate was 28 per cent for patients who had a D1 dissection, 63 per cent for those who had D2 and 68 per cent for those who had D4. These results suggest that extended lymphadenectomy (D2) and especially superextended lymphadenectomy (D4) can improve survival in patients with gastric cancer.     

Prognostic significance of proliferative activity and ploidy in node-negative breast cancers

Cardiac disease continues to be the leading cause of morbidity and mortality following peripheral vascular surgical procedures. Although the mechanism of sudden myocardial infarction remains elusive, many possibilities exist. The role of catecholamines is intriguing in view of the evidence that beta-adrenergic blockers reduce cardiac morbidity and mortality in vascular surgical patients. To ascertain whether the plasma catecholamine levels rise significantly during abdominal aortic aneurysm repair, serial determinations of plasma epinephrine and norepinephrine levels were performed in 18 patients. Epinephrine levels rose significantly from preoperative baseline values both during the operation and postoperatively, and norepinephrine levels rose significantly at 24 hours postoperatively. Although only one patient studied developed a myocardial infarction, the finding that patients undergoing aortic surgery uniformly experienced abnormally high serum catecholamine levels supports other evidence that perioperative myocardial ischemic events have a hormonal component.     

Prognostic significance of DNA flow cytometric analysis in patients with nasopharyngeal carcinoma

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a prevalent malignant tumor among Southern Chinese. Previously, the authors described the prognostic significance of a serum antibody assay to a recombinant Epstein-Barr virus Bam HI-Z replication activator protein (ZEBRA) in NPC patients with long term follow-up. In this study, the authors further reported the use of DNA flow cytometry (DNA-FCM) as an additional technique for determining the prognosis of NPC patients in the same series. METHODS: One hundred and forty-three archival biopsies from 110 NPC patients were deparaffinized and subjected to DNA-FCM analysis. DNA ploidy state and various proliferative indices (PI) of the tumors were correlated with patient survival and frequency of recurrence. RESULTS: Among the biopsies analyzed, 119 were histologically positive NPC and 24 were negative. Fifty-one tumor biopsies that fulfilled the guideline criteria of the DNA Cytometry Consensus Conference were correlated with the clinical manifestations of the patients. Among them, 43 tumors (84%) were DNA diploid and 8 (16%) were aneuploid. Two PI, S-phase fraction (SPF) and proliferation fraction (PF), appear to be potentially useful prognostic indicators. For example, PF in patients who developed locoregional recurrence (15.1%) and distant recurrence (16.4%) after radiation therapy both were significantly higher than PF in patients who were in complete remission (8.2%) (P = 0.0005 and P = 0.004, respectively). Significant differences in SPF between patients with distant recurrence (10.6%) and those in remission (5.7%) also was found (P = 0.005). Using Kaplan-Meier analysis, patients with high PF, high SPF, and aneuploid tumors had significantly poorer 12-year survival rates (35%, 26%, and 28%, respectively) than those patients with low PF, low SPF, and diploid tumors (77%, 67%, and 59%, respectively) (P < 0.0009, P < 0.004, and P < 0.01, respectively). CONCLUSIONS: Determination of tumor PI and DNA ploidy state by DNA-FCM at diagnosis of NPC can be potentially useful in selecting a poor prognostic subgroup of NPC patients. These parameters may enable oncologists to plan for more stringent treatment strategies such as hyperfractionated and accelerated radiation therapy or concomitant chemoradiotherapy for these patients.     

The prognostic significance of steroid receptor activity in tumor tissues of patients with primary breast cancer

The prognostic significance of steroid-receptor activity is still debatable. Discrepancies in results are probably attributable to few patients, heterogeneous patient populations, and short follow-up. We investigated the prognostic significance of estrogen- and progesterone-receptor (ER and PgR, respectively) activity as a continuous variable in a homogeneous patient population. The prognostic significance of steroid-receptor activity was examined in 329 node-negative and 320 node-positive unselected breast cancer patients. In node-negative patients, ER values of primary tumors between 100 and 400 fmol/mg protein appeared to be a significant predictor for low risk of recurrence, whereas high ER (> 400) revealed an unfavorable prognosis. The classic cutoff level of ER (< 10 fmol/mg proteins) had no prognostic significance, however. In patients receiving adjuvant chemotherapy--the node-positive breast cancer patients--the classic cutoff value of ER (10 fmol/mg protein) predicts significantly distant metastases-free survival and overall survival only in the first 4 years of follow-up after diagnosis. Progesterone receptor is a time-dependent prognosticator in node-negative breast cancer patients (cutoff point for PgR, 80 fmol/mg). In node-positive breast cancer patients treated with chemotherapy or a combination of chemo- and hormonal therapy, PgR values lower than 60 fmol/mg had a worse prognosis. The results show the poor performance of standard cutoff points for ER and PgR positivity in predicting prognosis. Better prognosis is related to higher receptor levels but this relation is predominantly time-dependent. Moreover, patients who have high ER levels have a prognosis that is worse when compared with intermediate ER levels. Standard cutoff points for steroid receptors should not be used to select patients for prognosis.     

Prognostic significance of the DNA index in a colorectal cancer

DNA flow cytometry was performed on paraffin-embedded tissue blocks made from 230 surgically resected colorectal cancers, 109 (47.4%) of which were diploid tumors, and 121 (52.6%) aneuploid tumors. The DNA index (DI) was calculated as the ratio of the G0/G1 channel number of tumor cells to the G0/G1 channel number of stromal cells. There was no significant difference in survival between patients with diploid tumors and those with aneuploid tumors (P = 0.322), although the survival rate was significantly lower in patients with a high DI (> or = 1.5) than in those with a low DI (< 1.5) (P = 0.004). A multivariate analysis of prognostic factors using Cox's proportional hazard model showed that Dukes' staging was the strongest predictor of survival, followed by the DI of tumor cells, then histological differentiation. In conclusion, it is suggested that the DI of tumor cells is instructive for predicting the survival of patients with colorectal cancer.     

Prognostic relevance of urokinase plasminogen activator detection in micrometastatic cells in the bone marrow of patients with primary breast cancer

The "attentional model" of time estimation assumes that temporal judgments depend on the amount of attention allocated to the temporal processor (the timer). One of the main predictions of this model is that an interval will be judged shorter when attention is not allocated to the temporal parameters of the task. Previous studies combining temporal and nontemporal tasks (dual-task method) have suggested that the time spent processing the target duration might be a key factor. The less time devoted by the subject to the temporal task, the shorter the judged duration. In the two experiments presented here, subjects were asked to judge both the duration of a visual stimulus and an increment in intensity occurring at any time during this stimulus. In the second experiment, trials without intensity increments were added. The main result is that the judged duration was shorter when the increment occurred later in the stimulus or did not occur. In those cases, subjects had been expecting increment occurrence during most part of the stimulus and thus had focused for a shorter time on stimulus duration. We propose that attention shifts related to expectancy and to detection of the increment reduce subjective duration.     

Prognostic significance of ST-T segment alterations in patients with non-Q wave myocardial infarction

Legionella jordanis has seldom been reported as a cause of infection in humans. We describe a case of pneumonia due to L. jordanis that occurred in a non-immunocompromised 74-year-old patient and failed to respond to a combination of ceftriaxone and ofloxacin. Cure was achieved only after an erythromycin-rifampin combination was started.