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PubMed1993

Incremental prognostic value of thallium imaging and coronary angiography in patients with a symptom-limited ECG stress test.

BACKGROUND: This study evaluates the incremental prognostic value of qualitative thallium-201 imaging and coronary angiography in patients with suspected or known coronary artery disease. METHODS: Within 1 month, 150 patients underwent diagnostic symptom-limited ECG stress test, thallium imaging, and coronary angiography. The incremental power of sequentially performed tests was evaluated by the overall likelihood ratio statistic. RESULTS: At 3-year follow-up, 16 patients had died from a cardiac cause, 12 had suffered a nonfatal myocardial infarction, and 34 had undergone revascularization procedures more than 60 days after testing. Considering hard events, thallium imaging did not improve the prognostic information provided by clinical exercise stress test data, while coronary angiography increased the predictive power of the combined, exercise stress test, and scintigraphic data (P < 0.001). Moreover, when thallium results were added to clinical, exercise, and coronary angiographic data, the predictive power was unchanged. When the analysis was repeated including the occurrence of late revascularization procedures, each test showed additional prognostic information to that obtained by the other combined tests (P < 0.001). CONCLUSIONS: This study demonstrates that in patients with a symptom-limited ECG stress test, coronary angiography adds prognostic information to combined clinical, exercise ECG, and thallium imaging data. The incremental prognostic value of qualitative thallium imaging is demonstrable only when late revascularization procedures are included as events.

Aged↗

PubMed2006

Accuracy of plasma levels of polymorphonuclear elastase as early prognostic marker of acute pancreatitis in routine clinical conditions.

OBJECTIVES: The early prognostic evaluation of acute pancreatitis (AP) is a key step in the appropriate management of the disease. Plasma levels of polymorphonuclear elastase have proved to be an accurate early prognostic marker of AP in research conditions. Whether the test remains sufficiently accurate in routine clinical conditions has been questioned. The aim of our study was to evaluate the accuracy of plasma polymorphonuclear-elastase levels for the early prognostic evaluation of AP in the clinical setting. METHODS: A total of 224 consecutive patients with AP admitted to our Gastroenterology Department were included. A blood sample for polymorphonuclear-elastase quantification was obtained from all of them in the first morning of hospital stay, together with samples for routine haematological and biochemical analysis. Blood samples for polymorphonuclear-elastase evaluation were sent to the laboratory and managed there according to routine protocols. AP was classified as mild or severe according to the Atlanta classification, whereas polymorphonuclear-elastase results were kept blind. Results were shown as mean+/-SD and compared using Student's t-test for unrelated samples. The accuracy of the test for the prognostic evaluation of AP was calculated after drawing the corresponding receiver operator curve. RESULTS: Fifty patients (23%) suffered from severe AP. The plasma levels of polymorphonuclear elastase were 217.8+/-93.5 microg/l in patients with severe AP and 68.1+/-32.7 microg/l in those with mild disease (P<0.001). The sensitivity and specificity of the test for the detection of severe AP were 92 and 91%, respectively, for an optimal cut-off value of 110 microg/l. The positive and negative predictive values for a prevalence of severe disease of 20% were 78 and 96%, respectively. The area under the receiver operator curve was 0.956. CONCLUSION: Quantification of plasma polymorphonuclear-elastase levels is a very accurate method for the early prognostic evaluation of AP, and is easily applicable in the clinical setting.

Acute Disease↗

PubMed1996

Prognostic markers in acute leukemia.

The identification of biologic markers for disease outcome in hematopoietic malignancies is essential for the development of "risk-adapted" therapies. Although new prognostic factors are frequently described, their real clinical and biologic impact is often difficult to determine. Factors that influence a marker's true prognostic value include several variables of study design: study size, uniform versus nonuniform patient treatment, methodologic variations, and correlations with other variables. Despite these concerns, several important prognostic factors have emerged in acute leukemias. For example, in acute myeloid leukemia, the multidrug resistant phenotype, whether conferred by the classic P-glycoprotein (multidrug resistance protein 1) or by other mechanisms, and cytogenetics are major prognostic indicators for outcome. In acute lymphoblastic leukemia, markers associated with loss of growth control (loss of tumor suppressor genes, increased proliferative fraction) likewise identify a group of poor-prognosis patients. The delineation of prognostic factors such as these allows for the better identification of patients who may benefit from risk-adapted therapies.

Acute Disease↗

PubMed2006

Transient evoked otoacoustic emissions pattern as a prognostic indicator for hearing preservation in acoustic neuroma surgery.

OBJECTIVE: To determine whether pre-operative transient otoacoustic emission (TEOAE) patterns are predictive of successful hearing preservation in acoustic neuroma surgery. STUDY DESIGN: Retrospective observational study. SETTING: Tertiary referral medical center. PATIENTS: A convenience sample was identified in whom pre-operative TEOAE data were available in patients undergoing acoustic neuroma surgery from 1993-2004. Ninety-three patients were identified who met this inclusion criterion. INTERVENTIONS: Subjects underwent attempted hearing preservation surgery via middle cranial fossa or retrosigmoid approaches. Routine audiometry, ABR, and TEOAE. MAIN OUTCOME MEASURES: Pre- and post-operative pure tone and speech results were categorized into hearing classes A, B, C, and D as described in the American Academy of Otolaryngology guidelines (1995). Hearing preservation was defined by maintenance of the pre-operative hearing class or downgrade to within one hearing class post-op. Pre-operative TEOAE results were divided into five frequency bands and described as positive in each band if there was a response above the noise floor with >50% reproducibility. RESULTS: Hearing was preserved in 51 patients (55%). Of these, 11 (22%) had positive TEOAE response in all five frequency bands measured (1, 1.5, 2, 3, 4 kHz), whereas 40 (78%) had TEOAE responses ranging from 0 to 4 frequency bands. 42 patients failed to preserve their hearing. Of these, only three (7%) had positive TEOAE in all five frequency bands, and 39 (93%) had TEOAE responses ranging from 0 to 4 frequency bands (p<0.05). Other variables of prognostic significance to hearing preservation in our series included smaller tumor size, tumor location within the IAC, better pre-operative hearing, and shorter latencies on ABR. Logistic regression was then used to compare the prognostic value of TEOAE against these variables. In our series, ABR latencies and 5 frequency band response on TEOAE showed the highest significant correlation to hearing preservation (p<0.05). CONCLUSION: A robust pre-operative TEOAE frequency band pattern may be used as a favorable prognostic indicator for potential hearing preservation in acoustic neuroma surgery. The prognostic value may be enhanced when combined with other prognostic factors such as tumor size, tumor location, pre-operative ABR and audiometric results.

Adolescent↗

PubMed2003

A critical appraisal of the prognostic value of the VE/VCO2 slope in chronic heart failure.

BACKGROUND: Increased ventilatory drive, reflected by the slope of increase of ventilation relative to carbon dioxide production (VE/VCO2 slope), has been shown to have a high prognostic value in patients with chronic heart failure (CHF). However, there is no consensus on how to calculate it, as the relation between VE and VCO2 becomes nonlinear near the end of exercise, when ventilation is driven both by CO2 output and by decrease in plasma pH. This may influence the results. METHODS: Ninety-seven CHF patients with ejection fraction <45% (mean 27 +/- 9%), in NYHA class II-IV underwent a cardiopulmonary exercise test. VE/VCO2 slope was assessed by linear regression using all the data points (Sl), using only points before (Sli), or after (Slf) the non-linear part of the curve, and using only the first 3-min data (Sl3 min). Peak oxygen uptake (VO2), and circulatory power (VO2 x systolic arterial pressure) were also assessed. Death and transplantation were the end-points considered (mean follow-up 22 months). RESULTS: Mean value of VE/VCO2 overall slope was 39.3 +/- 11.6 (22-78). In 64% of the patients, two distinct slopes could be found: an initial, linear slope (31.8 +/- 7.5, 18-62) and a final, steeper slope (48.6 +/- 15.7, 24-101). Patients in whom no rupture of slope was observed were sicker. There was a relation between initial and overall VE/VCO2 slopes (r=0.915, P<10(-4)) and between overall and 3-min VE/VCO2 slopes (r=0.808, P<10(-4)). VE/VCO2 slope correlated with peak VO2 (r=-0.55, P<10(-4)) and peak circulatory power (r=-0.49, P<10(-4)). Univariate analysis showed that the prognostic value of overall VE/VCO2 slope (chi2 25.4, P<10(-4)) was greater than initial (chi2 22.8, P<10(-4)), 3-min (chi2 14.6, P<10(-4)) or final VE/VCO2 slopes (chi2 6.7, P=0.09). By multivariate analysis, the prognostic value of the peak circulatory power was similar to that of the VE/VCO2 overall slope. CONCLUSIONS: The VE/VCO2 slope should be computed from all the data points to have its highest prognostic value. Peak circulatory power also has similar prognostic value.

Adult↗

PubMed2005

Clinical course and prognostic factors in acute low back pain: patients consulting primary care for the first time.

STUDY DESIGN: Inception cohort study. OBJECTIVES: To examine the clinical course of acute low back pain and to evaluate prognostic factors for nonrecovery. SUMMARY OF BACKGROUND DATA: Few studies have explored clinical course and prognostic factors in patients who consult primary care for their first time because of an episode of low back pain of <3 weeks duration. METHODS: A total of 123 patients with acute low back pain <3 weeks consulting primary care for the first time were included, and 120 completed 3 months follow-up. Baseline assessments included sociodemographic characteristics, back pain history and current status, psychological questionnaires and clinical examination. Main outcome measures were pain intensity, disability by Roland Morris Disability Questionnaire, and recovery of disability. Potential prognostic factors for recovery or not were analyzed by multivariate logistic regression. RESULTS: At 4 weeks and 3 months 76% of the patients had recovered. Mean pain intensity and mean disability scores dropped 58% and 68%, respectively, of initial levels during the 3 months. The proportion with sickness absence was 8% at 4 weeks and 6% at 3 months. Several sociodemographic, clinical, and psychological factors were of prognostic value. Compared with their respective reference categories, age above 45 years (odds ratio 4.4, 95% confidence interval 1.4-14.0), smoking (3.0, 1.1-8.5), two or more neurological signs (4.6, 1.4-14.9), a score of >or=90 on the psychosocial screening (3.1, 1.0-9.4), and high levels of distress (4.1, 1.3-12.8) were the best prognostic factors of nonrecovery at 3 months. CONCLUSION: During a period of 3 months, 24% of the patients had not recovered. Psychological factors and neurological signs were strongly associated with nonrecovery at 3 months. In addition to the traditional examination of neurological symptoms and signs, psychological factors should be considered already at the initial visit of an episode of low back pain.

Absenteeism↗

PubMed2006

Prognostic factors for patients with spinal metastases from lung cancer.

STUDY DESIGN: We conducted a retrospective study to identify prognostic factors of patients with spinal metastases from lung cancer. OBJECTIVE: To provide clinical data with strong association to the prognosis and to propose criteria determining indication of operation for spinal metastases. SUMMARY OF BACKGROUND DATA: To make a proper selection of patients for whom surgery is indicated, forecasting short-time survival after spinal metastases is very important. In the past, there has been no report of prognostic factors of patients with such metastases from this cancer. METHODS: This study included 114 patients with spinal metastases of lung cancer. Tumors were histologically categorized as non-small cell lung cancer (NSCLC) in 94 patients and small cell lung cancer (SCLC) in 20 patients. We investigated prognostic factors after spinal metastases using Cox comparative hazard model and a preoperative prognostic score proposed by Tokuhashi. We also investigated the patients who underwent operation for spinal metastases from lung cancer in our hospital. RESULTS: Multivariate analysis showed that the significant prognostic factors for survival after spinal metastases from NSCLC were performance status (PS), Ca, Alb. Among SCLC patients, Ca, Alb, and a history of chemotherapy were significant (P < 0.05) in univariate analysis. The score of Tokuhashi was not correlative to the survival period. Among the operated patients, postoperative PS was significant for the period of postoperative survival. CONCLUSION: PS, Ca, and Alb in NSCLC and Ca, Alb, and a history of chemotherapy in SCLC are useful for determining an indication of operation for spinal metastases from lung cancer.

Activities of Daily Living↗

PubMed2003

Waldeyer's ring lymphomas: treatment results and prognostic factors.

Optimal management of patients with localized Waldeyer's ring (WR) lymphoma remains controversial due to the lack of randomized studies and heterogenous grouping of most reported series. In this retrospective study, we have evaluated the possible prognostic factors and treatment outcome of WR non-Hodgkin's lymphoma. Between December 1993 and February 2000, 32 patients with WR lymphoma, stage I (11 patients) and stage II (21 patients) were treated. There were 17 male patients and 15 female patients with a median age of 47 years. The distribution among different anatomical sites were as follows: tonsils in 16 (50%), nasopharynx in 10 (31%), base of tongue in 6 (19%). According to Working Formulation, 10 had high-grade, 17 intermediate grade, 3 low-grade, and 2 had unclassified lymphomas. Combined chemotherapy and radiotherapy was the primary modality of therapy for intermediate or high-grade lymphoma. Radiotherapy alone was employed only in low-grade WR lymphomas. Chemotherapy was median 6 courses of CHOP (cyclophosphamide, doxorubicin (Adriamycin), vincristine, and prednisolone) in 26 patients and CEOP (cyclophosphamide, doxorubicin, etoposide, and prednisone). Radiotherapy volume was involved field and the median dose was 40 Gy. Median follow-up is 40 months (ranged from 6-82 months). Overall survival and disease-free survival (DFS) rates at 3 years are 100% and 92%, respectively. Two patients developed recurrence, both salvaged with further chemotherapy. Only one patient died because of other reasons. International Prognostic Index score ( 2) is found to be an important prognostic factor for DFS. The other significant prognostic factors for DFS are performance status and serum levels of alkaline phosphatase and lactate dehydrogenase. Our results suggest that combined chemotherapy and involved field radiotherapy is appropriate treatment for stage I-II WR lymphoma. International Prognostic Index is the strongest predictor for DFS.

Adult↗

PubMed2002

Adenocarcinoma of the small bowel: a study of 37 cases with emphasis on histologic prognostic factors.

PURPOSE: Primary small-bowel adenocarcinoma is uncommon. There are few large studies that have evaluated the prognostic impact of clinical and pathologic parameters. The purpose of this study was to perform a comprehensive analysis of the Cleveland Clinic experience with small-bowel adenocarcinoma, with emphasis on histopathologic parameters as prognostic indicators. METHODS: Thirty-seven cases of primary small-bowel adenocarcinomas resected at the Cleveland Clinic between 1978 and 1999 were retrospectively studied. Metastatic tumors and those arising from the biliary system were excluded from analysis. Clinical and pathologic data were recorded and their impact on prognosis was evaluated by either Kaplan-Meier or Cox proportional hazards analysis. RESULTS: The cohort included 25 males, and the age range was 24 to 82 (mean, 56) years. Tumor location was duodenum (18), jejunum (10), ileum (2), and site not specified (7). Patients most frequently presented with abdominal pain (48 percent), anemia (39 percent) and small-bowel obstruction (33 percent). Underlying conditions included Crohn's disease (4) and familial adenomatous polyposis (2). Overall survival was 52 and 47 percent at 5 and 10 years, respectively, with a mean follow-up of 50.5 (range, 0.5-184) months for all patients. Features found to be negative prognostic factors for survival were positive surgical margins (P < 0.001), extramural venous spread (P < 0.001), lymph node metastases (P = 0.038), poor tumor differentiation (P = 0.015), depth of tumor invasion (P = 0.023), and history of Crohn's disease (P < 0.001). Age, gender, tumor size, growth pattern, lymphocytic host response, and adjuvant therapy did not affect survival. CONCLUSIONS: Pathologic features, including positive surgical margins, extramural venous spread, positive lymph nodes, poor tumor differentiation, depth of tumor invasion, and history of Crohn's disease, are of major prognostic significance in small-bowel adenocarcinoma. Although many of these prognostic features are similar to the ones used for colorectal adenocarcinoma, they are easily applicable and reproducible for small-bowel adenocarcinomas. This is important considering the often dismal prognosis of small-bowel adenocarcinoma.

Adenocarcinoma↗

PubMed2003

Prognostic factors for survival with gemcitabine plus 5-fluorouracil based regimens for metastatic renal cancer.

PURPOSE: Combination gemcitabine and 5-fluorouracil (5-FU) may have activity in metastatic renal cell cancer. To identify patient subgroups most likely to benefit and compare survival to that in previously described patient series long-term survival as a function of known and suspected prognostic variables was determined. MATERIALS AND METHODS: The survival status of 153 patients with metastatic renal cell cancer treated on 1 phase I and 4 phase II trials of gemcitabine/5-FU based regimens was updated. Univariate and multivariate Cox proportional hazards models were constructed using multiple imputation for missing values. RESULTS: Performance status, prior nephrectomy, number of metastatic sites, decreased albumin and elevated alkaline phosphatase were highly prognostic for survival. Sarcomatoid differentiation and hypercalcemia had borderline prognostic significance. Using a previous described prognostic model that divided patients into 3 risk groups survival in those treated with gemcitabine/5-FU in this series was consistently better than survival in similar patients treated in the Motzer series. CONCLUSIONS: Previously described prognostic factors for survival in metastatic renal cancer were confirmed. There is no clearly identifiable group that is most likely to benefit from a gemcitabine/5-FU regimen but there is a continued suggestion that this regimen provides a modest improvement over historical chemotherapy approaches.

Antimetabolites, Antineoplastic↗

PubMed2004

Cadherin-6: a new prognostic marker for renal cell carcinoma.

PURPOSE: Cadherin-6, a new cell adhesion molecule of the cadherin family, is expressed in normal kidney and renal cell carcinoma. First results demonstrated that the expression of cadherin-6 in renal cell carcinoma may have prognostic value. We prospectively evaluated the importance of cadherin-6 in renal tumors in a large cohort of patients. MATERIALS AND METHODS: A total of 216 patients with renal cell carcinoma who underwent tumor nephrectomy were evaluated for cadherin-6 expression by immunohistochemistry and immunoblotting. The expression pattern was correlated with known prognostic factors of renal cell carcinoma. Statistical analysis was performed by the Mann-Whitney U and Pearson chi-square tests. Multivariate analysis was performed by the proportional hazard Cox model. RESULTS: Cadherin-6 expression in renal cell cancer correlated with known prognostic factors, such as pT stage (p = 0.03), pN stage (p = 0.001), histological growth pattern (p = 0.001), M stage (p = 0.06) and renal venous involvement (p = 0.019). There was no correlation with tumor grading (p = 0.74) or tumor size (p = 0.84). We developed a relative risk factor for renal cell cancer for our patients using the multivariate proportional hazard Cox model, which showed a statistically significant correlation with cadherin-6 expression (p = 0.028). CONCLUSIONS: Cadherin-6, a new cell adhesion molecule of the cadherin family, is specifically expressed in the proximal tubule of normal kidneys and in renal cell cancer. In our prospective analysis the pattern of cadherin-6 expression correlated with known prognostic factors of renal cell cancer on univariate and multivariate analysis. Our data suggest that cadherin-6 is a new prognostic factor for renal cancer.

Adolescent↗

PubMedDate not supplied

Longitudinal modifications of the MELD score have prognostic meaning in patients with liver cirrhosis.

BACKGROUND: The Model for End-Stage Liver Disease (MELD) score is an important and well established tool for assessing prognosis in patients with liver cirrhosis. It has been suggested that the longitudinal evaluation of the MELD score may reflect the progression of liver failure more reliably and therefore be more useful in prognostic assessment. AIM: To assess the prognostic meaning of MELD score modifications in a cohort of cirrhotic patients in whom clinical and biochemical workup was carried out at least twice during a minimum interval of 30 days. METHODS: Forty-six cirrhotic patients were longitudinally evaluated for a median follow-up of 365 days. After initial assessment, all the patients had at least one clinical and biochemical reevaluation during follow-up, which was performed no less than 1 month after initial evaluation. MELD was calculated at entry and at second evaluation. DeltaMELD was calculated as MELD at second evaluation minus MELD at entry. DeltaMELD/time was calculated as DeltaMELD divided by time elapsed between initial assessment and second evaluation expressed in months. RESULTS: During follow-up, 13 patients died (28%). The median interval between clinical evaluations was 120 days. MELD scores at entry (13 +/- 4 vs 16 +/- 6, P = 0.0516) and DeltaMELD (0 +/- 4 vs 4 +/- 2, P = 0.0028) were significantly different between patients who died and those who survived during the 1-year follow-up. All the patients who died during follow-up showed an increase of at least 1 unit in DeltaMELD/time (sensitivity = 100%), and all the patients who survived showed a decrease of more than 1 unit in DeltaMELD/time (specificity = 100%). CONCLUSIONS: Longitudinal evaluation of the MELD score provides important prognostic information that seems to complete the prognostic definition provided by "static" MELD. Prospective studies in larger series are needed to validate the prognostic use of MELD modifications over time.

Adult↗

PubMed2004

Outcome and prognostic factors of acute lymphoblastic leukemia in children at the National Cancer Institute, Egypt.

OBJECTIVE: To improve survival of children with acute lymphoblastic leukemia (ALL) in the authors' institute and to define significant prognostic factors. METHODS: This study included 154 children with newly diagnosed ALL below the age of 18 years during the period August 1, 1998, to December 31, 2000. All patients were treated according to the NCI, Cairo, Egypt, treatment protocol modified from study XIII for high-risk ALL of St. Jude Children's Research Hospital. RESULTS: B-cell precursor phenotype was encountered in 73.4% of patients, T-cell in 26.6%. According to NCI/Rome criteria for risk classification, 58.4% of patients were in the high-risk group (90% of T-lineage compared with 47% of B-lineage ALL, P < 0.001). Nine patients (5.8%) died during induction and 10 patients (6.5%) failed to achieve remission. With a median follow-up of 43 months, the 3-year disease-free survival and its probability at 5 years were 80 +/- 3.6% and 75.3 +/- 4%, respectively; the 3-year event-free survival and its probability at 5 years were 69 +/- 3.8% and 65.2 +/- 4%, respectively. B-cell precursor ALL had 5-year probabilities of disease-free survival and event-free survival of 80.5 +/- 4% and 71.8 +/- 4.5% compared with 60.2 +/- 8.6% and 46.7 +/- 8% for T-cell, respectively (P < 0.01, log-rank test). Prognostic factors that had a statistically significant unfavorable impact on survival by univariate analysis were age 10 years or more, central nervous system involvement, T-lineage phenotype, high-risk group, DNA index less than 1.16, and slow early response to treatment. By multivariate analysis, central nervous system involvement, high-risk group, and slow early response to treatment still had prognostic significance. Risk classification demonstrated prognostic significance for B-lineage but not T-lineage ALL. CONCLUSIONS: This treatment protocol was effective in improving ALL survival among patients at the authors' institute compared with previous trials, although the outcome remains lower than that in more industrialized countries. Prognostic factors defined in this study were similar to those identified by other cooperative groups.

Academies and Institutes↗

PubMed2004

Nucleolar organizer regions as a prognostic indicator in epithelial cancers of the ovary.

Recent studies have shown that quantification of silver-stained nucleolar organizer region associated proteins (AgNORs) is correlated with ploidy and proliferative activity in several neoplasms. The prognostic value of this marker, however, has not been well defined in epithelial ovarian carcinomas (EOCs). We studied 84 cases of EOCs in an attempt to assess the potential prognostic significance of AgNORs and to compare the results with other prognostic factors in EOCs. Clinical, operative and treatment details, and follow-up data were recorded for each case. In univariate analysis, a highly significant correlation of AgNOR count with clinical stage (p < 0.01), histologic grade (p < 0.05), response to chemotherapy (p < 0.05), and biologic behavior (p < 0.01) was found. High AgNOR counts were observed in late stage (III and IV) tumors, grade 3 carcinomas, tumors in patients with partial response to chemotherapy, progressive disease, recurrence, or death from tumor. In multivariate analysis, AgNOR count at cut off 3.5 was found to be the third prognostic variable after response to therapy and stage. These observations suggest that AgNOR count holds promise for prediction of tumor aggressiveness in EOCs. However, its role as an independent prognostic variable of patient survival remains questionable.

Adolescent↗

PubMed2005

Development of a tissue array for primary melanoma with long-term follow-up: discovering melanoma cell adhesion molecule as an important prognostic marker.

Refining current prognostic capability is essential for improving the management of melanoma. This study was undertaken to develop a tumor array for the rapid assessment of novel prognostic markers in a series of specimens from melanoma patients with 7- to 10-year follow-up. A melanoma database of 120 patients with archival specimens was created after histopathological review of original specimens. A tissue array was developed allowing 480 biopsy samples from the 120 primary melanoma specimens to be embedded into a single paraffin block. This was sectioned and stained for the adhesion marker melanoma cell adhesion molecule (MCAM); after further review, 76 of the 120 specimens were suitable for further analysis. The slides were assessed by two independent observers without previous knowledge of the clinical outcome for staining positivity and stain intensity. Assessment of association between MCAM and clinicopathological features was carried out using chi-squared analysis, and univariate and Cox multivariate analyses were performed on the data. There was a high correlation between MCAM intensity and both Clark's level and Breslow thickness (Spearman correlation p < 0.001 for both). The data revealed that MACM was a highly specific prognostic marker for survival in univariate analysis (chi2 = 18, p < 0.0001). Subgroup analysis by stratification of the staining intensity revealed a sequentially worsening survival with increasing staining intensity (chi2 = 22.33, p < 0.0001). Multivariate analysis of survival showed MCAM to be an independent prognostic marker more accurate than all other clinicopathological parameters (p < 0.0001), including the Breslow depth. Further analysis within only intermediate-thickness tumors showed MCAM intensity added further refinement to outcome prediction (chi2 = 22.33, p < 0.0001). The tissue array provided a rapid method of analyzing up to 480 specimens within a single paraffin block. This will benefit many areas of plastic surgery research. The identification of adhesion markers revealed a valuable prognostic marker for predicting outcome and a potential target for therapeutic manipulation.

Adult↗

PubMed2003

Clinical significance of angiogenesis in gastrointestinal cancers: a target for novel prognostic and therapeutic approaches.

OBJECTIVE: To review the current data on the prognostic and therapeutic implications of tumor angiogenesis in gastrointestinal cancers. SUMMARY BACKGROUND DATA: Numerous studies have evaluated the prognostic value of tumor angiogenesis and the potential role of antiangiogenic therapy in various gastrointestinal cancers. METHODS: A Medline literature search was conducted using "angiogenesis" or the names of various angiogenic factors in combination with the names of gastrointestinal cancers as the key words. RESULTS: Several studies have demonstrated a significant prognostic impact of tumor microvessel density and tumor expression of angiogenic factors, in particular vascular endothelial growth factor (VEGF), in various gastrointestinal cancers. A few studies have suggested that circulating VEGF might be a useful prognostic marker. However, results were not consistent across all studies and were limited by the retrospective nature of most studies. Antiangiogenic therapy has been shown to be effective against all common gastrointestinal cancers in preclinical studies, but currently there are few clinical data with regard to antiangiogenic therapy in gastrointestinal cancers. CONCLUSIONS: There is mounting evidence to suggest that assessment of tumor angiogenesis might provide a novel approach of prognostication in patients with gastrointestinal cancers. However, current results from retrospective studies need to be validated by prospective studies. Antiangiogenic therapy is a promising strategy of cancer treatment that might be particularly useful in combination therapy for unresectable cancers or as an adjuvant therapy for resectable tumors.

Angiogenesis Inhibitors↗

PubMed2004

Prognostic value of lymphangiogenesis and lymphovascular invasion in invasive breast cancer.

OBJECTIVE: The aim of this study was to investigate the prognostic relevance of lymphangiogenesis and lymphovascular invasion in a large cohort of breast cancer patients. INTRODUCTION: Invasion of tumor cells into blood and lymphatic vessels is one of the critical steps for metastasis. The presence or absence of lymph node metastasis is one of the main decision criteria for further therapy. One shortcoming of previous morphologic studies was the lack of specific markers that could exact discriminate between blood and lymphatic vessels. The aim of this study was to evaluate the prognostic relevance of lymphangiogenesis and lymphovascular invasion in breast cancer patients. METHODS: We investigated 374 tissue specimens of patients suffering from invasive breast cancer by immunostaining for the lymphatic endothelial specific marker podoplanin. Lymphangiogenesis, quantified by evaluating the lymphatic microvessels density (LMVD), and lymphovascular invasion (LVI) were correlated with various clinical parameters and prognostic relevance. RESULTS: LMVD correlated significantly with LVI (P = 0.001). LVI was associated significantly with a higher risk for developing lymph-node metastasis (P = 0.004). Calculating the prognostic relevance, LVI presented as an independent prognostic parameter for disease free as well as overall survival (P = 0.001, and P = 0.001, respectively). CONCLUSION: Our data provide evidence that the biologic system of lymphangiogenesis constitutes a potential new target for development of anti-breast cancer therapeutic concepts. Our results further suggest that young, premenopausal patients with low differentiated breast tumors and high LMVD and LVI would, in particular, benefit from lymphangiogenesis-associated therapeutic strategies.

Adult↗

PubMed2004

A new prognostic staging system for rectal cancer.

OBJECTIVE: To clarify the appropriateness of tumor "budding," a quantifiable histologic variable, as 1 parameter in the construction of a new prognostic grading system for rectal cancer. SUMMARY BACKGROUND DATA: Patient division according to an accurate prognostic prediction could enhance the effectiveness of postoperative adjuvant therapy and follow-up. PATIENTS AND METHODS: Tumor budding was defined as an isolated cancer cell or a cluster composed of fewer than 5 cells in the invasive frontal region, and was divided into 2 grades based on its number within a microscopic field of x250. We analyzed 2 discrete cohorts comprising 638 and 476 patients undergoing potentially curative surgery. RESULTS: In the first cohort, high-grade budding (10 or more foci in a field) was observed in 30% of patients and was significantly associated with a lower 5-year survival rate (41%) than low-grade budding (84%). Similarly, in the second cohort, the 5-year survival rate was 43% in high-grade budding patients and 83% in low-grade budding patients. In both cohorts, multivariate analyses verified budding to be an independent prognosticator, together with nodal involvement and extramural spread. These 3 variables were given weighted scores, and the score range was divided to provide 5 prognostic groups (97%; 86%; 61%; 39%; 17% 5-year survival). The model was tested on the second cohort, and similar prognostic results were obtained. CONCLUSIONS: We propose that because of its relevance to prognosis and its reproducibility, budding is an excellent parameter for use in a grading system to provide a confident prediction of clinical outcome.

Adenocarcinoma↗