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Platelet function in patients with acute coronary syndrome (ACS) predicts recurrent ACS.

BACKGROUND: Platelet hyperfunction contributes to acute coronary syndromes (ACS). Thus, we hypothesized that platelet function under high shear stress predicts recurrent ACS during long-term follow-up of ACS patients. PATIENTS AND METHODS: Consecutive ACS patients (n = 208) were prospectively followed-up for an average of 28 months. Platelet function was measured with the platelet function analyzer (PFA-100; Dade Behring, Marburg, Germany) at baseline for collagen/adenosine diphosphate closure times (CADP-CT) and for collagen/epinephrine closure times (CEPI-CT) after infusion of a uniform dose of 250 mg aspirin. RESULTS: Of the conventional risk factors, only the prevalence of diabetes was higher in ACS patients with re-events. However, use of clopidogrel and use of beta blockers were also slightly lower in patients with re-events (P < 0.05). The unadjusted risk hazard ratio (HR) for re-events was 3.3 [95% confidence interval (95% CI): 1.4-7.4; P = 0.005] in those patients with the shortest CADP-CT values (lowest quartile). Similarly, the risk was 2.0-fold higher (95% CI: 1.1-3.6; P = 0.02) in ACS patients with CEPI-CT < 300 s as compared with CEPI-CT >or = 300 s. Inclusion of diabetes, clopidogrel and beta blockers in a multivariate Cox regression model enhanced the predictive value of CEPI-CT (HR: 2.7). Inclusion of von Willebrand factor levels did not alter the HR for recurrent ACS (HR: 2.1; 95% CI: 1.1-5.2; P = 0.03) for CEPI-CT < 300 s, but reduced the HR for CADP-CT (HR: 2.8, 95% CI: 0.8-9.8; P = 0.11). CONCLUSION: Shortened CT values reflect biologically relevant platelet hyperfunction in patients with ACS because they predict recurrent ACS.

Acute Disease↗

A validation of two preoperative nomograms predicting recurrence following radical prostatectomy in a cohort of European men.

Kattan et al. at Baylor College of Medicine and D'Amico et al. at Harvard Medical School have each developed preoperative nomograms for prostate cancer recurrence after radical prostatectomy based on readily available clinical variables. Calibration and validation of those tools was achieved using North American patient cohorts, and their validity has not yet been shown in patients from other continents. We investigated the predictive accuracy of these nomograms when applied to European men with localized prostate cancer. Clinical data from patients who underwent radical prostatectomy at the University-Hospital Hamburg and fitted the respective derivation criteria were used for external validation (n = 1003 for the Kattan-Nomogram, n = 932 men for the D'Amico-Nomogram). Nomogram predictions of the probability for 2-years and 5-years freedom from recurrence predicted by the D'Amico-Nomogram and the Kattan-Nomogram respectively were compared with actual follow-up. The predictive accuracy of the nomograms was tested using areas under the receiver-operating-characteristic curves (AUC). The D'Amico-Nomogram AUC predicting 2-years probability of freedom from PSA recurrence was 0.80 vs. Kattan-Nomogram 5-years prediction with an AUC of 0.83. Using the 932 patients who exactly fit the derivation criteria of both nomograms, the predictive accuracy of the Kattan-Nomogram was 0.81. The superiority in predictive accuracy of the Kattan-Nomogram was statistically significant (p = 0.0274) but of unclear clinical significance. The two nomograms predicted recurrence with similar accuracy when applied to men diagnosed with localized prostate cancer in Germany. The high predictive accuracy of both nomograms demonstrates that these predictive tools derived in the U.S. can be applied to non-U.S. patients.

Cohort Studies↗

[Predicting recurrent pterygium based on morphologic and immunohistologic parameters].

BACKGROUND: Independently of the technique for excision used, pterygia recur quite frequent. We investigated whether recurrences can be predicted by means of histological and immunohistological parameters. MATERIALS AND METHODS: In a prospective clinical investigation the frequency of recurrent pterygia after excision and subsequent autologous limbal grafting was studied. The pterygia of 10 patients without recurrence (mean follow-up time 13 months) were compared retrospectively and semiquantitatively with the pterygia of 7 patients who had a recurrence. The following parameters were taken into consideration: (1) elastoid degeneration; (2) amount of vascularization; (3) morphological signs of "dry eye" (e.g., loss of goblet cells, beginning keratinization); (4) reactive inflammation; (5) amount of CD1a-, CD4-, CD8- and CD68-positive cells; (6) expression of PDGFalpha, PEDGFbeta, EGF, and laminin receptors. RESULTS: No appreciable differences between recurrent and nonrecurrent pterygia were found. CONCLUSION: As adjuvant therapeutic strategies like application of mitomycin C or beta-irradiation may lead to complications, it would be desirable it they could be limited to patients at risk. The histological and immunohistological parameters investigated probably do not allow prediction of pterygial recurrence. Consequently, they are not helpful in deciding whether adjuvant therapy should be started or not.

Adult↗

A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer.

BACKGROUND: The likelihood of distant recurrence in patients with breast cancer who have no involved lymph nodes and estrogen-receptor-positive tumors is poorly defined by clinical and histopathological measures. METHODS: We tested whether the results of a reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay of 21 prospectively selected genes in paraffin-embedded tumor tissue would correlate with the likelihood of distant recurrence in patients with node-negative, tamoxifen-treated breast cancer who were enrolled in the National Surgical Adjuvant Breast and Bowel Project clinical trial B-14. The levels of expression of 16 cancer-related genes and 5 reference genes were used in a prospectively defined algorithm to calculate a recurrence score and to determine a risk group (low, intermediate, or high) for each patient. RESULTS: Adequate RT-PCR profiles were obtained in 668 of 675 tumor blocks. The proportions of patients categorized as having a low, intermediate, or high risk by the RT-PCR assay were 51, 22, and 27 percent, respectively. The Kaplan-Meier estimates of the rates of distant recurrence at 10 years in the low-risk, intermediate-risk, and high-risk groups were 6.8 percent (95 percent confidence interval, 4.0 to 9.6), 14.3 percent (95 percent confidence interval, 8.3 to 20.3), and 30.5 percent (95 percent confidence interval, 23.6 to 37.4). The rate in the low-risk group was significantly lower than that in the high-risk group (P<0.001). In a multivariate Cox model, the recurrence score provided significant predictive power that was independent of age and tumor size (P<0.001). The recurrence score was also predictive of overall survival (P<0.001) and could be used as a continuous function to predict distant recurrence in individual patients. CONCLUSIONS: The recurrence score has been validated as quantifying the likelihood of distant recurrence in tamoxifen-treated patients with node-negative, estrogen-receptor-positive breast cancer.

Algorithms↗

Increased anticardiolipin antibody IgG titers do not predict recurrent stroke or TIA in children.

BACKGROUND: Increased anticardiolipin antibody (ACLA) immunoglobulin (Ig) G titers are commonly found in children with arterial ischemic stroke (AIS) or TIA (AIS/TIA). The associated risk of recurrent thromboembolism is unknown. OBJECTIVE: To determine the risk of recurrent thromboembolism associated with persistently increased ACLA titers of the IgG isotype in children with AIS/TIA. METHODS: The authors studied a cohort of children surviving first AIS/TIA tested by standardized ELISA for beta2-glycoprotein I-dependent ACLA of the IgG isotype. Children with ACLA titers >15 IgG phospholipid (GPL) units (per manufacturer's cutoff point) on more than two occasions > or =6 weeks apart were classified as ACLA-positive (ACLA+) and compared with ACLA-negative (ACLA-) children with respect to recurrent thromboembolic events (AIS/TIA, sinovenous thrombosis, and extracerebral thromboembolism). RESULTS: The authors recruited 34 ACLA+ children and 151 ACLA- children. Most ACLA+ children (30/34; 88%) had ACLA titers < or =40 GPL units. During the follow-up period (median duration, 2.8 years for ACLA+ children and 3.0 years for ACLA- children), AIS/TIA recurred in 26% of ACLA+ children and in 38% of ACLA- children; none developed sinovenous thrombosis or extracerebral thromboembolism. Based on survival analysis, this difference was nonsignificant (p = 0.54). Using binary partition evaluation, no titer criteria for ACLA positivity (range, 0 to 60 GPL units) predicted recurrent AIS/TIA. CONCLUSION: In children surviving arterial ischemic stroke/TIA, increased anticardiolipin antibody immunoglobulin G titers do not predict recurrent thromboembolism.

Antibodies, Anticardiolipin↗

Predicting recurrence and metastasis of Dukes' A primary colorectal cancer with or without proper muscle invasion.

This study compared the prediction of recurrence based on detection of occult neoplastic cells (ONCs) in lymph nodes or using 3 criteria to identify high-risk patients among 72 patients who had Dukes' A colorectal cancer with or without proper muscle invasion. Predicting recurrence based on the detection of ONCs had a sensitivity of 40.0% (2/5) and a false-negative rate of 60.0% (3/5), while there was a specificity of 97.0% (65/67) and false-positive rate of 3.0% (2/67), resulting in an accuracy of 68.5%, PPV of 50.0% (2/4), and NPV of 95.6% (65/68). Predicting recurrence based on the presence of at least 2 of the 3 high-risk criteria showed a sensitivity of 60.0% (3/5) and a false-negative rate of 40.0% (2/5), while it had a specificity of 74.6% (50/67) and a false-positive rate of 25.4% (17/67), resulting in an accuracy of 67.3%, PPV of 15.0% (3/20), and NPV of 96.2% (50/52). These results suggest that a prediction based on ONCs was similar to use of the high-risk criteria, with both methods having a high specificity for recurrence/metastasis of Dukes' A colorectal cancer.

Colorectal Neoplasms↗

A prognostic model for clinical stage I melanoma of the upper extremity. The importance of anatomic subsites in predicting recurrent disease.

Thirteen variables were studied for their relative usefulness in predicting recurrent disease in 107 patients with clinical Stage I melanoma of the upper extremity. After a mean follow-up period of 54 months, the only patents who have had recurrent disease to date are those who primary lesions were located either on the hand or posterior upper arm. The five-year disease-free survival role for 44 patients with melanoma at these sites was 68%. None of 63 patients with melanoma located on the forearm of anterior upper arm have had recurrent disease (i.e., the five-year, disease-free survival rate was 100% (p = 0.00004), compared with the hand or posterior arm group). A Cox proportional hazards (multivariate) analysis demonstrated that two primary tumor histologic variable, thickness in millimeters and ulceration, interacted to produce the best prognostic model for those 44 patients with melanoma of the hand or posterior upper arm. Twenty-one patients with primary lesions at these sites had primary tumors less than 2.25 mm in thickness and no evidence of ulceration histologically. Their five-year, disease-free survival role was 95%. For the remaining 23 patients with primary tumors on the hand or posterior upper arm who had either histologic evidence of ulceration or primary tumors greater than or equal to 2.25 mm, the five-year disease-free survival rate was 37% (p = 0.002, compared with group nonulcerated, thin lesions). The excellent survival rate for patients with melanomas on the forearm or anterior upper arm was not completely explained by pathologic stage, by primary tumor thickness, or by histologic ulceration of the primary tumor.

Arm↗

p53 and bcl-2 immunohistochemistry in pretreatment prostate needle biopsies to predict recurrence of prostate cancer after radical prostatectomy.

PURPOSE: Immunohistochemical staining of radical prostatectomy specimens for p53 and bcl-2 proteins has been shown to correlate with prostate specific antigen (PSA) recurrence in a series of patients at our institution. We analyzed the relationship between staining of diagnostic prostate needle biopsies for p53 and bcl-2, and PSA recurrence. MATERIALS AND METHODS: From 1986 to 1993, 335 radical prostatectomies were performed at our hospital. Of the prostatectomy specimens 199 had been evaluated for p53 and bcl-2 proteins in a prior series. Of 139 patients with biopsy material available for analysis 129 had enough for evaluation of 1 or both markers. Prospectively obtained clinical followup data were available, with a mean followup of 6 years. Commercially available antibodies were used for immunohistochemical staining. RESULTS: The overall PSA recurrence rate was 37.6% for 199 radical prostatectomy cases and 37.9% for 129 with biopsy immunohistochemical staining. Staining of prostatectomies correlated well with PSA recurrence for p53 (p = 0.004) and bcl-2 (p = 0.001). However, biopsy staining did not correlate with prostatectomy staining or PSA recurrence for either marker. CONCLUSIONS: The p53 and bcl-2 biomarkers appear to be important to predict recurrence of prostate cancer when prostatectomy specimens are analyzed but this usefulness is not apparent with immunohistochemical staining of prostate biopsies. This difference may reflect sampling error and/or the heterogeneous nature of prostate cancers, and deserves further study.

Aged↗

The 21-gene recurrence score assay as a tool for predicting recurrence risk and guiding adjuvant treatment selection in early breast cancer.

INTRODUCTION: Estrogen receptor-positive (ER+), HER2-negative breast cancer is the most common breast cancer subtype. While adjuvant endocrine therapy reduces recurrence risk, identifying which patients benefit from the addition of chemotherapy remains a key clinical challenge. The Oncotype DX&#xae; 21-gene Recurrence Score assay (Exact Sciences, via Genomic Health, Inc.) was developed to address this by quantifying distant recurrence risk and informing chemotherapy decisions in early-stage ER+/HER2- disease. AREAS COVERED: This diagnostic profile reviews the development, validation, and clinical evidence for Oncotype DX, including findings from the TAILORx and RxPONDER prospective trials and the subsequent development of hybrid tools integrating genomic and clinicopathological data. Alternative multiparameter molecular tests (MammaPrint, Prosigna, EndoPredict, Breast Cancer Index) are summarized and compared. We review international guideline recommendations, decision impact studies, cost-effectiveness evidence, and ongoing trials. EXPERT OPINION: Oncotype DX has strong prognostic evidence and has meaningfully reduced chemotherapy use, though its case as a biomarker predictive of therapeutic effect from chemotherapy rests on trial designs with important limitations. Its independent prognostic contribution beyond comprehensive clinicopathological assessment requires further clarification, and cost-effectiveness varies substantially by indication and healthcare setting.

Humans↗

Visual estimate of percent of carcinoma predicts recurrence after radical prostatectomy.

PURPOSE: Tumor volume is an important prognosticator for predicting prostate cancer recurrence following radical prostatectomy (RP). We assessed the ability of the visual estimate of the percent of carcinoma (VEPC) to predict recurrence. METHODS AND MATERIALS: As performed by 1 surgeon (MSS), 1,114 men underwent radical prostatectomy between 1992 and February 2002. Patients who had less than 12 months of followup, who underwent salvage RP or in whom VEPC was not assessed in the pathology specimen were excluded. VEPC and other clinical variables were analyzed. We performed univariate analysis using the Kaplan-Meier log rank test. Multivariate analysis using Cox proportional hazards regression was performed. RESULTS: A total of 692 patients with a mean age of 61 +/- 7 years met the criteria for this analysis. Mean followup was 52 +/- 30 months. Of the patients 17% had biochemical recurrence. Mean VEPC was 25% and 13% in those with and without recurrence, respectively. On univariate analysis all variables were significant predictors of recurrence. However, multivariate analysis showed that the only significant predictors of recurrence were patient age, initial prostate specific antigen 10 ng/ml or greater, RP Gleason 8 to 10, extraprostatic extension, seminal vesicle involvement and VEPC. Based on disease-free survival curves patients were stratified into 3 broad groups, namely low, intermediate and high volume. The HR for biochemical recurrence was 2.1 for the intermediate VEPC group (9.1% to 20%) and 2.7 for the high VEPC group (greater than 20%). In the reference group it was less than 9% (low volume). CONCLUSIONS: VEPC is a simple and inexpensive method that is an independent predictor of recurrence after RP.

Follow-Up Studies↗

Nuclear morphometry accurately predicts recurrence in clinically localized renal cell carcinoma.

Despite careful clinical staging, as many as 30 percent of patients with pathologically, specimen-confined renal cell carcinoma (RCC) have unpredictable recurrence following surgery. Present pathologic and clinical staging systems cannot accurately predict those patients with high risk of disease recurrence from those who are cured by surgery alone. Advances in immunotherapy including gene therapy for RCC have dictated the need to identify RCC patients for adjuvant therapy protocols who have a high probability of recurrence following nephrectomy. Nuclear morphometric techniques developed at our institution have predicted prognosis for a variety of genitourinary tumors; it was used to predict recurrence among patients undergoing nephrectomy for localized RCC. This report is a retrospective study of 26 patients with RCC of similar age, stage (pT1-pT3), and grade. Fifteen were free of disease at a mean of 75.2 months, and 11 had distant disease recurrence at a mean of 27.1 months. Statistical analysis of a variety of nuclear shape descriptors accurately separated this group of patients based on disease recurrence. No nuclear shape descriptor predicted disease recurrence when nuclei within the region of the tumor with the highest grade were analyzed. However, the range of nuclear ellipticity (p = 0.007) best predicted disease recurrence when nuclei were selected in a random fashion. Multivariate analysis of the four best shape descriptors better predicted disease recurrence (p = 0.002) with a sensitivity of 73 percent and specificity of 100 percent. These results are encouraging and suggest that this technique might be used in identifying patients for adjuvant gene therapy.

Adult↗

Tumor angiogenesis predicts recurrence with normal serum carcinoembryonic antigen in advanced rectal carcinoma patients.

Many studies have established the usefulness of serum carcinoembryonic antigen (CEA) oriented serial monitoring for predicting recurrence and prognosis; however, few studies have so far investigated serum CEA-negative recurrence. The aim of this study was to elucidate the nature of CEA-negative recurrence regarding tumor angiogenesis. Fifty-seven patients with T3/T4 rectal cancer were divided into the two groups according to the serum CEA status. Angiogenesis was defined as the intratumoral vessel count by immunohistochemical staining using CD31. The CD31 count was significantly higher in the recurrent patients in both groups and the ratio of nodal involvement was significantly higher in the recurrent patients of the CEA-negative group. Local recurrence mainly developed in the CEA-negative group; however, the CD31 count did not predict the sites of recurrence nor the relapse period in the both groups. A multivariate analysis showed a high CD31 count >26) to be a prognostic factor not only for recurrence but also for survival (P = 0.001, 0.043, respectively). These results suggest that a high degree of tumor angiogenesis in sections of T3/T4 rectal cancer may therefore be an important predictor for CEA-negative recurrence.

Adenocarcinoma↗

A postoperative prognostic nomogram predicting recurrence for patients with conventional clear cell renal cell carcinoma.

PURPOSE: Few published studies have simultaneously analyzed multiple prognostic factors to predict recurrence after surgery for conventional clear cell renal cortical carcinomas. We developed and performed external validation of a postoperative nomogram for this purpose. We used a prospectively updated database of more than 1,400 patients treated at a single institution. MATERIALS AND METHODS: From January 1989 to August 2002, 833 nephrectomies (partial and radical) for renal cell carcinoma of conventional clear cell histology performed at Memorial Sloan-Kettering Cancer Center were reviewed from the center's kidney database. Patients with von Hippel-Lindau disease or familial syndromes, as well as patients presenting with synchronous bilateral renal masses, or distant metastases or metastatic regional lymph nodes before or at surgery were excluded from study. We modeled clinicopathological data and disease followup for 701 patients with conventional clear cell renal cell carcinoma. Prognostic variables for the nomogram included pathological stage, Fuhrman grade, tumor size, necrosis, vascular invasion and clinical presentation (ie incidental asymptomatic, locally symptomatic or systemically symptomatic). RESULTS: Disease recurrence was noted in 72 of 701 patients. Those patients without evidence of disease had a median and maximum followup of 32 and 120 months, respectively. The 5-year probability of freedom from recurrence for the patient cohort was 80.9% (95% confidence interval 75.7% to 85.1%). A nomogram was designed based on a Cox proportional hazards regression model. Following external validation predictions by the nomogram appeared accurate and discriminating, and the concordance index was 0.82. CONCLUSIONS: A nomogram has been developed that can be used to predict the 5-year probability of freedom from recurrence for patients with conventional clear cell renal cell carcinoma. This nomogram may be useful for patient counseling, clinical trial design and effective patient followup strategies.

Carcinoma, Renal Cell↗

Impact of p53 and Ki-67 in predicting recurrence and progression of superficial (pTa and pT1) urothelial cell carcinomas of urinary bladder.

In predicting the aggressive behavior of bladder tumors, the histopathological characteristics of grade and invasive stage are of principal importance. However, for predicting tumor recurrence and progression, these are sufficient only to a limited extent, particularly in the case of superficial (pTa and pT1) urothelial cell carcinomas. New prognostic factors are therefore needed to avoid either insufficient or excessive treatment. In this retrospective study, we investigated the prognostic value of the p53 and Ki-67 immunoreactivity indices. The present study included 118 superficial urinary bladder tumors consisting of 58 recurrent and 60 non-recurrent cases. Twenty of the recurrent tumors progressed into a higher grade and/or invasive stage. Paraffin immunohistochemical analysis was carried out using anti-p53 and anti-Ki-67 antibodies on the initial tumor tissues. We concluded that there is a highly significant relationship between the p53 and Ki-67 immunoreactivities and the histological grade and pathological stage of the tumors (P < 0.0001). We observed a significant relationship between the presence of recurrence and progression and the p53 immunoreactivity index (P < 0.01 and P = 0.017, respectively) and Ki-67 immunoreactivity index (P < 0.0001 and P = 0.046, respectively). Positivity for p53 and Ki-67 can demonstrate the risk of recurrence (p53: sensitivity = 76%, specificity = 58%; Ki-67: sensitivity = 86%, specificity = 48%) and progression (p53: sensitivity = 80%, specificity = 46%; Ki-67: sensitivity = 85%, specificity = 36%; ). We believe that both of these immunohistochemical markers can be considered valuable in addition to classical histopathological prognostic parameters for predicting recurrence and progression risks.

Adult↗

A multigene RT-PCR assay used to predict recurrence in early breast cancer: two presentations with contradictory results.

During the 2003 San Antonio Breast Cancer Symposium two studies were presented that were designed to validate a recurrence score, derived from a 21-gene RT-PCR assay, in patients with axillary node-negative breast cancer. This recurrence score was highly predictive for the risk of recurrence in 668 patients treated in a large multicenter trial with adjuvant tamoxifen. However, no prognostic value was found in a small group of patients who were retrospectively selected in a single institution and who did not receive any adjuvant systemic therapy. Further validation is needed to establish the prognostic and predictive role of this assay in clinical management.

Breast Neoplasms↗

Does angiogenesis predict recurrence in superficial transitional cell carcinoma of the bladder?

OBJECTIVES: To investigate the role of angiogenesis in predicting tumor recurrence and its correlation with established clinicopathologic prognostic factors in superficial transitional cell carcinoma of the bladder. METHODS: The paraffin sections of 80 superficial papillary transitional cell bladder carcinoma specimens were stained with CD31 antibody to label the vascular endothelium using the standard streptavidin-biotin-immunoperoxidase method. The vascular surface density (VSD) equivalent to the vascular surface area per unit of tissue volume and number of vessels per square millimeter of stroma (NVES) were assessed by means of stereology, and these morphometric parameters of angiogenesis were statistically analyzed to interpret the relation to tumor recurrence in addition to tumor stage, grade, size, and number and the presence of carcinoma in situ. RESULTS: VSD and NVES values showed no statistically significant difference between pTa and pT1 tumors or patients with and without recurrence. In contrast, VSD and NVES values were found to increase in higher grade tumors (P = 0.019). VSD values were also higher in patients with coexisting carcinoma in situ in pTa tumors (P <0.001). Tumor number and size and recurrence number and time to the first recurrence did not correlate with any vascular parameters. CONCLUSIONS: Stereologic assessment of angiogenesis does not help to predict recurrence in superficial bladder cancer. Angiogenic parameters appeared to be well correlated with the conventional histologic grading system. Otherwise, the present study did not show any correlation of angiogenesis with any potential prognostic factors. This may be due to the diverse angiogenic pathways occurring in invasive and superficial tumors.

Adult↗

Role of circulating tumour cells in predicting recurrence after excision of primary colorectal carcinoma.

BACKGROUND: This study assessed the potential for reverse transcriptase-polymerase chain reaction (RT-PCR)-based circulating tumour cell identification to predict colorectal cancer recurrence. METHODS: mRNA for carcinoembryonic antigen and cytokeratin 20 was identified by RT-PCR in blood from patients with colorectal cancer, before and after primary tumour resection. Cancer recurrence was assessed at follow-up, and the accuracy of RT-PCR and primary tumour lymph node positivity in predicting recurrence was estimated. RESULTS: One hundred and ninety-six patients with colorectal cancer were studied over a median follow-up of 1393 days from surgery. Regression analysis selected 24-h post-resection RT-PCR positivity (hazard ratio for a positive test in predicting recurrence 8.66 (95 per cent confidence interval (c.i.) 3.08 to 24.33)) before lymph node involvement (hazard ratio 7.92 (95 per cent c.i. 3.26 to 19.20)). When 24-h post-resection RT-PCR was combined with lymph node positivity, the hazard ratio increased to 18.54 (95 per cent c.i. 4.01 to 85.11), attributing a 3 per cent recurrence risk to 52 per cent, and a 50 per cent recurrence risk to 48 per cent, of patients with colorectal cancer resected with curative intent. CONCLUSION: RT-PCR positivity within 24 h of primary colorectal cancer resection is a strong predictor of colorectal cancer recurrence, and may be useful clinically.

Aged↗

Role of microvessel density in predicting recurrence in pathologic Stage T3 prostatic adenocarcinoma.

OBJECTIVES: Extraprostatic extension of prostatic adenocarcinoma (pathologic Stage T3) increases the risk of recurrence after radical prostatectomy compared with organ-confined prostate cancer. Use of microvessel density in predicting cancer recurrence in Stage pT3 cancer is poorly understood. We evaluated known predictors of recurrence, including Gleason grade, preoperative serum prostate-specific antigen (PSA), DNA ploidy, seminal vesicle involvement, and surgical margin status in comparison with optimized microvessel density (OMVD) and area-weighted microvessel density (AWMVD) in patients with Stage pT3 prostate cancer. METHODS: Between 1987 and 1989, 290 previously untreated patients underwent radical prostatectomy and were found to have pathologic Stage T3 adenocarcinoma. No patient received adjuvant therapy. Embedded prostatectomy specimens from 211 patients with sufficient tissue for immunohistochemical staining with factor VIII-related antigen were studied by computer-assisted digital image analysis for OMVD and AWMVD. The correlation of Gleason grade, preoperative PSA, DNA ploidy, seminal vesicle involvement, surgical margin positivity, OMVD, and AWMVD with clinical or biochemical failure was assessed using the Cox proportional hazards model. Biochemical failure was defined as a postoperative increase in PSA greater than 0.2 ng/mL, and clinical failure was defined as a positive biopsy or metastasis on bone scan. RESULTS: The mean follow-up +/- SD for all patients was 7.1 +/- 1.8 years, with 43 deaths (9 due to prostate cancer) and 124 cases of clinical and/or biochemical recurrence. The mean OMVD was 65.0 +/- 17.3, and the mean AWMVD was 8.2 +/- 5.3. OMVD and AWMVD were not predictors of cancer recurrence or significantly associated with DNA ploidy or preoperative PSA. AWMVD was associated with Gleason grade (P = 0.003). The estimated relative risk (adjusted for other cancer variables) of clinical and biochemical recurrence associated with a change in OMVD from the 25th percentile (53.5) to the 75th percentile (75.4) was 1.14 (95% confidence interval 0.92 to 1.42). The estimated relative risk (adjusted) of clinical and biochemical recurrence associated with a change in AWMVD from the 25th percentile (4.8) to the 75th percentile (10.4) was 1.17 (95% confidence interval 0.97 to 1.42). Gleason grade, preoperative PSA, DNA ploidy, and seminal vesicle involvement were predictors of clinical and/or biochemical recurrence in univariate and multivariate analyses. CONCLUSIONS: Microvessel density, assessed by OMVD and AWMVD, did not predict recurrence in patients with pathologic Stage T3 adenocarcinoma of the prostate (TNM Stage T3N0M0). DNA ploidy, Gleason grade, preoperative PSA, and seminal vesicle involvement remained the best predictors of clinical and/or biochemical recurrence in this group of patients.

Adenocarcinoma↗