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Predicting recurrence and metastasis of stage III/Dukes' C colorectal cancer with lymph node metastasis.

This study was designed to compare the prediction of recurrence based on detection of occult neoplastic cells (ONCs) in lymph nodes or using specific criteria to identify patients at high risk of recurrence/metastasis among 105 patients with Dukes' C colorectal cancer. Prediction of recurrence based on the detection of ONCs had a sensitivity of 50.0% (22/44), specificity of 80.3% (49/61), and an accuracy of 65.2%. Prediction of recurrence based on positivity for at least 2 of the 3 high-risk criteria had a sensitivity of 54.5% (24/44), specificity of 83.6% (51/61), and an accuracy of 69.1%. Among the 34 patients with ONCs, prediction of recurrence based on positivity for all 3 high-risk criteria had a sensitivity of 27.3% (6/22), specificity of 91.7% (11/12), an accuracy of 59.5%, and a positive predictive value (PPV) of 85.7% (6/7). These results suggest that the predictive value of ONCs and the high-risk criteria was similar, and that recurrence is likely to occur in patients who fulfill < or =2 of the high-risk criteria. Accordingly, combined use of these parameters may be more effective for the early prediction of recurrence/metastasis to assist in the choice of postoperative systemic chemotherapy.

Colorectal Neoplasms↗

Predicting recurrence and metastasis of stage II/Dukes' B colorectal cancer without lymph node metastasis.

This study was designed to compare the prediction of recurrence based on detection of occult neoplastic cells (ONCs) in lymph nodes or by using high-risk criteria for recurrence/metastasis in patients with Dukes' B colorectal cancer. Prediction of recurrence based on the detection of ONCs had a sensitivity of 59.1% (13/22), a false-positive rate of 7.8% (8/102), a specificity of 92.2% (94/102), and a negative predictive value (NPV) of 91.3% (94/103). Prediction of recurrence based on positivity for at least 2 of the 3 high-risk criteria had a sensitivity of 90.9% (20/22), a false-positive rate of 49.0% (50/102), a specificity of 51.0% (52/102), and an NPV of 96.3% (52/54). Among the 21 patients in whom ONCs were detected, prediction of recurrence based on the presence of all 3 high-risk criteria including ONCs had a sensitivity of 84.6% (11/13) and a positive predictive value (PPV) of 78.6% (11/14). These results suggest that colorectal cancer is unlikely to recur in patients without ONCs, while recurrence is likely in patients who fulfill 2 or more of the high-risk criteria. Accordingly, a combination of these parameters may be useful for the early prediction of recurrence/metastasis to assist in the choice of postoperative systemic chemotherapy.

Colorectal Neoplasms↗

Histopathologic score predicts recurrence free survival after radical surgery in patients with stage IA2-IB1-2 cervical carcinoma.

BACKGROUND: The authors evaluated clinical and pathologic factors that predicted for recurrence after patients underwent radical surgery for International Federation of Gynecology and Obstetrics (FIGO) Stage IA(2)-IB(1-2) cervical carcinoma and developed a simple method of scoring those predictive factors to quantify outcome. METHODS: An analysis was conducted of a prospective radical surgery cervical carcinoma data base. A Cox proportional hazards regression analysis was done for each of the individual factors to estimate individual risk ratios using all available data for each factor. Stepwise and best-model options were used to identify the best combinations as predictors and to calculate adjusted risk ratios. Based on the information obtained, each patient was assigned a categorical score to predict recurrence. The variables used for the score were dichotomized. The differences between the scores in time to recurrence were evaluated using the log-rank test to compare the time to recurrence curves that were generated with the Kaplan-Meier method. RESULTS: Eight hundred seventy-one patients were included in the study, and 66 patients who developed recurrent disease after a median follow-up of 49 months. Tumor size, maximum depth of invasion, pelvic lymph node status, tumor grade, and capillary lymphatic space (CLS) were single predictors for recurrence, and the score, which was based on combinations of these factors, predicted the disease free survival. Maximum depth of invasion, pelvic lymph node status, and CLS were the best combined predictors for recurrence, and they were used to form a second, precise scoring system to predict disease free survival (P < 0.0001; log-rank test). CONCLUSIONS: The scoring system based on maximal depth of invasion, CLS, and pelvic lymph node metastases identified four strata of patients with distinct recurrence free survival. The incremental presence of each factor decreased recurrence free survival after patients underwent radical surgery. Patients with the presence of all three factors had a 5-year recurrence free survival rate of 65%. These patients would be suitable for studies of postoperative adjuvant therapy to improve outcome.

Adult↗

Tumor angiogenesis predicts recurrence in invasive colorectal cancer when controlled for Dukes staging.

Tumor angiogenesis is associated with metastasis in several types of solid tumors, including melanoma, breast, prostate, lung, bladder, and oral-cavity tumors. The purpose of this study was to determine whether tumor angiogenesis could predict recurrence following curative surgery for colorectal cancer. Thirty-five patients were studied, including 13 patients with recurrent tumor and 22 without. Representative formalin-fixed, paraffin-embedded sections of invasive colorectal cancers from these patients were sectioned. The endothelial cells of microvessels within the tumors were highlighted by immunohistochemical staining for CD31. The most active areas were identified and the microvessels counted in a x 400 field (0.152 mm2) by two observers in a blinded fashion. Tumor microvessel count (p = 0.0062). Dukes' staging (p = 0.0004), vascular invasion (p = 0.0280), and tumor grade (p = 0.0559) were all significantly associated with tumor recurrence. Tumor microvessel counts > or = 65 per x 400 field were associated with tumor recurrence (p = 0.0035, relative risk [RR] = 11.3). Controlling for Dukes' stage, a multivariate logistic regression model revealed that a tumor microvessel count > or = 65 is an important predictor of tumor recurrence (p = 0.0783, RR = 6.0). A backwards elimination proportional hazards model revealed that a microvessel count > or = 65 shows a trend toward independent prediction of time to tumor recurrence (p = 0.1203, RR = 2.967) when controlled for Dukes' staging (p = 0.0029, RR = 9.089). Despite the small number of patients studied, these results suggest that the number of microvessels in sections of invasive colorectal adenocarcinoma immunohistochemically stained with CD31 may be an important independent predictor of tumor recurrence and time to recurrence.

Adenocarcinoma↗

Gene-expression profiling predicts recurrence in Dukes' C colorectal cancer.

BACKGROUND & AIMS: Although approximately 50% of Dukes' C colorectal cancer patients are surgically cured, it is currently not possible to distinguish these patients from those at high risk of recurrence. The recent advent of routine adjuvant chemotherapy for these patients has greatly complicated the identification of new markers predicting the response to surgery, which is now reliant on archived materials. Microarray analysis allows fine tumor classification but cannot be used with paraffin-embedded archival samples. METHODS: We used microarray analysis of a unique set of fresh-frozen tumor samples from Dukes' C patients who had surgery as the only form of treatment to identify molecular signatures that characterize tumors from patients with good and bad prognosis. RESULTS: Unsupervised hierarchical clustering and a K-nearest neighbors-based classifier identified groups of patients with significantly different survival (P = .019 and P = .0001). Expression profiling outperformed previously reported genetic markers of prognosis such as TP53 and K-RAS mutational status and allelic imbalance in chromosome 18q, which were of limited prognostic power in this study. Functional categories significantly enriched in gene-expression differences included protein transport and folding. The prognostic potential of the RAS homologue RHOA, one of the most differentially expressed genes, was further investigated using immunohistochemistry and a tissue microarray containing 137 independent Dukes' C tumor samples. Reduced RHOA expression was associated with significantly shorter survival (P = .01). CONCLUSIONS: This study shows that gene-expression profiling of surgical tumor samples can predict recurrence in Dukes' C patients. Therefore, this approach could be used to guide decisions concerning the clinical management of these patients.

Aged↗

Value of high-density lipoprotein (HDL) subpopulations in predicting recurrent cardiovascular events in the Veterans Affairs HDL Intervention Trial.

OBJECTIVE: To test the hypothesis whether determination of high-density lipoprotein (HDL) subpopulations provides more power to predict recurrent cardiovascular disease (CVD) events (nonfatal myocardial infarction, coronary heart disease death, and stroke) than traditional risk factors in the Veterans Affairs HDL Intervention Trial (VA-HIT). METHODS AND RESULTS: Apolipoprotein A-I (apoA-I)-containing HDL subpopulations were quantitatively determined by nondenaturing 2D gel electrophoresis. Hazard ratios of recurrent CVD events were calculated by comparing VA-HIT subjects with (n=398) and without (n=1097) such events. Subjects with new CVD events had significantly lower HDL-C, apoA-I, and large cholesterol-rich HDL particle (alpha-1, alpha-2, pre-alpha-1, and pre-alpha-2) levels, significantly higher triglyceride, and small poorly lipidated HDL particle (pre-beta-1 and alpha-3) levels than subjects without such events. Multivariate analyses indicated that alpha-1 and alpha-2 particle levels were significant negative risk factors, whereas alpha-3 level was a significant positive risk factor for new CVD events. Pre-beta-1 level was a significant risk factor for new CVD events only in univariate analysis. A forward selection model indicated that alpha-1 was the most significant risk factor for recurrent CVD events among HDL particles. CONCLUSIONS: An altered HDL subpopulation profile marked with low alpha-1 and alpha-2 levels and a high alpha-3 level in coronary heart disease patients indicated an elevated risk for new CVD events. Moreover, alpha-1 and alpha-2 levels were superior to HDL-C levels in risk assessment in patients with low HDL-C in VA-HIT.

Aged↗

Can biological markers predict recurrence and progression of superficial bladder cancer?

Biological markers that are predictive of recurrence and progression of superficial bladder tumors must provide additional information to that provided by multiplicity, size and grade. Field anomalies in normal appearing urothelium of patients with papillary superficial transitional cell carcinoma have been associated with tumor antigens and chromosome 9 deletions. Also, primary tumors with chromosome 9 deletions are associated with a higher risk of recurrence. Abnormal expression of p53, p21 and Ki-67 cell cycle markers have little predictive value for recurrence. However, p53 overexpression or mutation and decreased expression of p27 are associated with cancer progression and survival. New markers, such as mutations in the fibroblast growth factor receptor 3 gene (found in 30% of tumors), anomalies of the PTEN gene and vascular endothelial growth factor expression, may have potential and require further evaluation. Molecular fingerprints of superficial tumors with distinct clinical behavior are being rapidly unravelled. Large-scale clinical studies are urgently needed to provide supportive evidence for their incorporation in clinical management.

Biomarkers, Tumor↗

ODC mRNA as a prognostic factor for predicting recurrence in meningiomas.

In proliferating neoplastic cells, activity of the enzyme ornithine decarboxylase (ODC) increases. Among other brain tumors, ODC activation could also be observed in meningiomas. In the present study, we have investigated ODC gene expression in primary and recurrent meningiomas at the transcriptional level. ODC mRNA (messenger ribonucleic acid), ODC activity, number of mitoses, and Ki-67 index as a marker for nuclear proliferation were quantified in three different groups of meningiomas: tumors without recurrence in a 8.4 years median follow-up period, tumors with recurrence within a median follow-up of 3.0 years, and their corresponding recurrent tumors. ODC mRNA level was significantly higher in meningiomas with later recurrence as compared to meningiomas without recurrence (p < or = 0.01), whereas it declined in the recurrences of the second group (p < or = 0.001). In contrast, ODC activity showed no difference between the two groups of primary tumors, but a significant increase of enzyme activity could be observed in the recurrences as compared to the correponding primary tumors (p < or = 0.001). Likewise, an increase of the Ki-67 index could be detected in the recurrent group (p < or = 0.001). These results suggest that ODC mRNA may represent a prognostic factor for predicting recurrence in meningiomas.

Adult↗

Hostility predicts recurrent events among postmenopausal women with coronary heart disease.

Psychosocial characteristics may be associated with an increased risk of coronary heart disease (CHD). Whether hostility predicts recurrent coronary events is unknown. A total of 792 women in the Heart and Estrogen/progestin Replacement Study (HERS) were evaluated prospectively to determine the role of hostility as a risk factor for secondary CHD events (nonfatal myocardial infarction and CHD death). The mean age of study participants was 67 years, and the average length of follow-up was 4.1 years. The study was conducted between 1993 and 1998, and all study sites were in the United States. High Cook-Medley hostility scores were associated with greater body mass index (p = 0.01) and higher levels of serum triglycerides (p = 0.05), and they were inversely associated with high density lipoprotein cholesterol (p = 0.04), self-rated general health (p < 0.001), age (p = 0.05), and education (p = 0.001). Compared with women in the lowest hostility score quartile, women in the highest quartile were twice as likely to have had a myocardial infarction (relative hazard = 2.03, 95% confidence interval: 1.02, 4.01). The relation between hostility and CHD events was not mediated or confounded by the biologic, behavioral, and social risk factors studied. In this study, hostility was found to be an independent risk factor for recurrent CHD events in postmenopausal women.

Aged↗

The association between levels of cortisol secretion and fear perception in patients with remitted depression predicts recurrence.

This study examines the association between cortisol secretion and fear perception in remitted patients to identify mechanisms underlying risk for recurrence of depression. We hypothesized that the stronger the association between cortisol secretion and fear perception in persons with remitted depression, the more recurrence would be experienced. We also investigated whether high levels of cortisol and fear perception per se predict more recurrence. These effects were assumed to be stronger in women than in men. In a prospective design, we investigated 77 outpatients with remitted depression and related the association between their 24-hour urinary free cortisol secretion and fear perception (from ambiguous faces and from vocal expressions) to recurrence of depression within 2 years. We applied Cox regression models, partial correlations, and Fisher z tests. In 21 patients, depression recurred. Irrespective the channel of perception (eye or ear), the interaction between fear perception and cortisol secretion was significantly related to recurrence of depression. Patients high or low on both variables are more at risk. This increased risk was also reflected by a significant association between cortisol secretion and facial fear perception, but only among subjects who experienced recurrence. A trend in the same direction was found for vocal fear perception. Fear perception and cortisol secretion per se did not predict recurrence. No gender differences were found. The association between cortisol secretion and fear perception (probably indicative for altered fear circuits in the brain) constitutes a mechanism underlying risk for recurrence of depression.

Adult↗

Tissue Doppler imaging analysis at pre-cardioversion time predicts recurrent atrial fibrillation: a 12-month follow-up study.

INTRODUCTION: Tissue Doppler imaging (TDI) has been extensively used in several clinical settings. We aimed to investigate whether TDI can predict recurrent atrial fibrillation (AF). METHODS AND RESULTS: Seventy-four consecutive patients (aged 62.6 +/- 11.7 years) with AF (>48 hours and <6 months of duration) who underwent successful external electrical direct current cardioversion and 20 healthy individuals were enrolled. Conventional echocardiography and TDI were prospectively performed before cardioversion. Based on a cutoff point of 5.43 cm/sec for the negative systolic wave velocity (NSWV), derived by the normal controls (mean + 2 SD), patients were divided into Group I (36 patients) with a NSWV >5.43 cm/sec and Group II (38 patients) with NSWV 48 hours; all patients were in AF at 12 months. In Group II, all patients were in sinus rhythm at 12 months. However, those patients presenting with a NSWV less but near to 5 cm/sec had frequent episodes of asymptomatic paroxysmal AF lasting for <48 hours. CONCLUSION: One year after successful direct current cardioversion, TDI analysis at pre-cardioversion time may be a useful marker to identify a subgroup of patients with increased risk for AF recurrence.

Aged↗

The use of digital image analysis of chromatin texture in Feulgen-stained nuclei to predict recurrence of low grade superficial transitional cell carcinoma of the bladder.

BACKGROUND: Identifying a marker enabling prediction of recurrence in the group of superficial transitional cell carcinomas (sTCCs) of the bladder remains an important challenge today. This report quantitatively describes chromatin patterns with respect to such sTCC recurrence. MATERIALS AND METHODS: Twenty-nine patients with sTCCs who did not exhibit tumor recurrence within a minimum of 24 months were compared with 21 patients with sTCCs who exhibited tumor recurrence two or three times in a 24-month period, for a total of 74 sTCCs. Quantitative chromatin pattern description was performed by the digital cell image analyses of Feulgen-stained nuclei. Six morphonuclear parameters were thus described and subsequently used to determine a score, allowing biological behavior of sTCCs to be described, i.e., recurrence versus non-recurrence in one calculation step. DNA ploidy level was also determined in each sTCC by assessing its DNA histogram type. RESULTS: Of 32 patients with Grade 1 pathologically classified pTa/pT1 tumors, DNA ploidy level determination permitted correct prediction of tumor nonrecurrence or recurrence of 13 (41%), whereas determination of the score values enabled prediction of nonrecurrence or recurrence of 25 (78%). Combining DNA ploidy level data and the score values enabled recurrence or nonrecurrence to be predicted for 29/32 of the patients (91%). CONCLUSIONS: The quantitative description of chromatin patterns by digital cell image analysis of Feulgen-stained nuclei can provide helpful information, in addition to DNA ploidy level determination, in predicting tumor recurrence of low grade superficial transitional cell carcinomas of the bladder.

Carcinoma, Transitional Cell↗

Balance score and a history of falls in hospital predict recurrent falls in the 6 months following stroke rehabilitation.

OBJECTIVE: To investigate predictors of recurrent falls in adults who return to community dwelling after stroke rehabilitation. DESIGN: Prospective observational study. SETTING: Community. PARTICIPANTS: Fifty-five adults with stroke (mean age +/- standard deviation, 68.1+/-12.8y). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Baseline measures included balance, gait speed, muscle strength and tone, activity level, hemianopia, visual contrast sensitivity, hemineglect, medication use, fear of falling, and depression. Participants kept a 6-month prospective falls diary after discharge from rehabilitation. RESULTS: Twenty-five (45%) participants reported falling, 12 had recurrent falls (> or =2 falls), and 13 fell once. Participants who fell recurrently had histories of falling during hospitalization or rehabilitation, poorer physical function measures, were taking more medications, and were more likely to have hemineglect than participants who fell once or did not fall (P<.05). A history of falling in the hospital or during rehabilitation, combined with poor balance (either Berg Balance Scale score <49 or step test score <7), predicted recurrent falls with sensitivity and specificity values greater than 80%. CONCLUSIONS: Falls are a common occurrence after stroke. The predictive model developed can be used to identify people who are likely to have recurrent falls in the 6 months after stroke rehabilitation.

Accidental Falls↗

The role of transvaginal sonography in predicting recurrent preterm labour in patients with intact membranes.

Our purpose was to determine whether funnelling of the cervical internal os, length of the endocervical canal, cervical index, funnel length and funnel width determined by transvaginal sonography are predictive of recurrent preterm labour. Of 112 women, 65 admitted to the hospital for preterm labour with intact membranes had transvaginal sonographic evaluation of the cervix before digital cervical examination and institution of tocolysis. The following measurements were obtained: (1) presence of funnelling, (2) endocervical canal length, (3) cervical index, (4) funnel length and (5) funnel width. Logistic regression analysis was performed to determine the variables that made a significant contribution to the prediction of recurrent preterm labour. A total of 65 eligible women completed the study. Recurrent preterm labour was significantly associated with the presence of funnelling (85.2% vs. 23.3%) and short endocervical canal length, large cervical index and long funnel length as noted on transvaginal cervical sonography. The presence of funnelling, shorter endocervical canal length, larger cervical index and longer funnel length were suggestive of true preterm labour and its recurrence. Transvaginal sonographic examination of the uterine cervix is a useful procedure to predict recurrent preterm labour with intact membranes.

Cervix Uteri↗

The use of risk indices: do they predict recurrence? Yes, they (at least some) do.

A suitable and advisedly used risk index is an effective tool for improving prevention, therapy monitoring and classification of almost unmanageable amounts of analysis data and diagnoses. In contrast to statistically founded indices, causality-based risk indices can provide a fundamental insight into the mechanisms of the underlying pathology. However, understanding of stone formation as the result of many linked and often non-linear individual processes must be further improved. Only in this way can risk indices be optimized or better ones be developed. We are confident that, with consistent research efforts, science will be able to predict recurrence of stone formation more accurately within the next couple of years.

Humans↗

Relative levels of SCCA2 and SCCA1 mRNA in primary tumors predicts recurrent disease in squamous cell cancer of the head and neck.

Squamous cell carcinoma antigen (SCCA) is widely used as a serum marker in cancers of the uterine cervix, the head and neck, lung and esophagus. Two isoforms of SCCA, deriving from 2 highly homologous serine proteinase inhibitor genes, are co-expressed in normal and malignant squamous epithelium, but it is mainly the acidic isoform SCCA2 that is present in the circulation of cancer patients. We studied the relative levels of SCCA2 and SCCA1 mRNA in frozen sections of squamous cell carcinomas of the head and neck (SCCHN) in relation to disease recurrence, using a new reverse transcription-polymerase chain reaction-based technique for accurate quantitation of relative mRNA levels. Primary tumors from 30 SCCHN patients, recurrent tumors from 11 patients and normal epithelium from 16 controls were examined. In patients responding to initial therapy (n = 26), an elevated SCCA2/SCCA1 mRNA ratio in the primary tumor predicted recurrence independent of clinical stage (p = 0.011). The relative risk of developing a recurrence was 7.2 (CI 1.2-13.3) in patients with elevated vs. normal SCCA2/SCCA1 mRNA ratios. We demonstrate that subtle differences in expression levels of the SCCA genes are reflected in the course of the SCCHN disease and may provide a target for molecular grading of SCCHN tumors. If this finding can be confirmed in a larger study the SCCA2/SCCA1 mRNA ratio in primary tumors could be useful for individual selection of treatment strategy for patients with head and neck cancer.

Adult↗

Characteristics that predicted recurrence of infarction within 3 years in the Ontario Exercise-Heart Collaborative Study.

Data on 13 baseline characteristics of 618 patients who had previously had a myocardial infarction and who had entered the Ontario Exercise-Heart Collaborative Study were analysed for their ability to predict recurrence of infarction within 3 years. These characteristics were age, serum levels of cholesterol and triglycerides, systolic and diastolic blood pressure, number of hours of competitive sports per week, number of hours of jogging per week, angina, type of occupation, smoking, cough and phlegm production, personality type and the number of previous infarctions. The characteristics showing independent statistical significance (p less than 0.05) were smoking and blue-collar occupation, with estimated adjusted relative odds of 2.3 and 2.1 respectively.

Adult↗

Early predicting recurrent cervical cancer with combination of tissue polypeptide specific antigen (TPS) and squamous cell carcinoma antigen (SCC).

The establishment of new tumor marker combinations including strong lead-time effects in detecting recurrent cervical cancer appears to be warranted. This retrospective study includes 50 patients with recurrent squamous cell cervical cancer after operation or radiotherapy. The serial serum levels of the tumor markers tissue polypeptide specific antigen (TPS) and squamous cell carcinoma antigen (SCC) were determined. Cutoff values of 78.5 U/L for TPS and 1.5 microg/L for SCC were selected according to the 95th percentile of serum concentrations measured in healthy control patients. Comparing with other monitoring modalities, SCC and TPS showed lead-time effective in 27 and 30 cases, respectively. This difference was not statistically significant. The combination of SCC and TPS provided lead-time effects in 42 cases. Our data indicate that combination of TPS and SCC is a valuable tool in the early predicting recurrent cervical cancer.

Adult↗