Significance Of Margins Research Articles

On the Significance of the Absolute Margin

Consider the hypothesis H that a defendant is guilty (a patient has condition C), and the evidence E that a majority of h out of n independent jurors (diagnostic tests) have voted for H, and a minority of k ≕ n − h against H. How likely is the majority verdict to be correct? By Condorcet's formula, the probability that H is true given E depends only on each juror's competence and on the absolute margin between the majority and the minority h − k, but neither on the number n, nor on the proportion h/n. This paper reassesses that result and explores its implications. First, using the classical Condorcet jury model, I derive a more general version of Condorcet's formula, confirming the significance of the absolute margin, but showing that the probability that H is true given E depends also on an additional parameter: the prior probability that H is true. Second, I show that a related result holds when we consider not the degree of belief we attach to H given E, but the degree of support E gives to H. Third, I address the implications for the definition of special majority voting, a procedure used to capture the asymmetry between false positive and false negative decisions. I argue that the standard definition of special majority voting in terms of a required proportion of the jury is epistemically questionable, and that the classical Condorcet jury model leads to an alternative definition in terms of a required absolute margin between the majority and the minority. Finally, I show that the results on the significance of the absolute margin can be resisted if the so-called assumption of symmetrical juror competence is relaxed. 1. Introduction2. The classical Condorcet jury model and the Condorcet jury theorem3. The significance of the absolute margin for the degree of belief we attach to the hypothesis given the evidence4. The significance of the absolute margin for the degree of support the evidence gives to the hypothesis5. An implication for the definition of special majority voting5.1 Making positive decisions if and only if the truth of the hypothesis is beyond any reasonable doubt5.2 Tracking the truth in the limit5.3 Summary6. The jury model without the assumption of symmetrical competence7. Concluding remarks

Positive proximal (bladder neck) margin at radical prostatectomy confers greater risk of biochemical progression

Objectives To identify the prognostic significance of positive bladder neck margin as the sole positive margin after radical retropubic prostatectomy for treatment of prostate cancer. Methods We retrospectively analyzed the data from patients who underwent radical retropubic prostatectomy at Johns Hopkins Hospital between 1984 and 2001. Of 164 patients with positive margins, 38 had a positive margin only at the bladder neck margin and 126 had a positive margin at one or more locations separate from the bladder neck margin. Results Kaplan-Meier analyses showed that patients with a positive bladder neck margin had a greater biochemical progression risk than patients with positive margins at one or more locations other than the bladder neck margin. The 5-year actuarial risk of progression in men with positive and negative bladder neck margins was 69.8% and 33.0%, respectively. A positive bladder neck margin was statistically an independently significant predictor of progression ( P = 0.001), along with the prostatectomy Gleason score ( P = 0.0001) in the multivariate analysis. The hazard ratio for predicting progression for postoperative Gleason score and bladder neck positivity was 2.1 and 2.5, respectively. Serum prostate-specific antigen values, clinical stage, age, and the percentage of tumor at the bladder neck margin were not predictors of progression in either univariate or multivariate analysis. Conclusions Patients with a positive bladder neck margin as the sole positive margin at radical retropubic prostatectomy have a greater risk of biochemical progression than patients with one or more positive margins at other locations, although not as adverse as the risk reported for those with Stage T4 disease.

Significance of margins of excision on breast cancer recurrence (on behalf of the EORTC Radiotherapy, Breast Cancer Groups)

Significance of margins of excision on breast cancer recurrence (on behalf of the EORTC Radiotherapy, Breast Cancer Groups)

175 Prognostic significance of positive surgical margins in organ-confined and extraprostatic prostate cancer after radical retropubic prostatectomy

175 Prognostic significance of positive surgical margins in organ-confined and extraprostatic prostate cancer after radical retropubic prostatectomy

The prognostic significance of margin width for extremity and trunk sarcoma

To evaluate the significance of resection margin for soft tissue sarcoma (STS), we determined local recurrence-free interval (LRFI), distant metastases-free interval (DMFI), and overall survival (OS) for primary extremity and truncal STS with clear margins (> or =10 mm), close margins (1-9 mm), and positive margins (0 mm). Patients were evaluated via review of charts and tumor specimens. Among 111 patients, tumors were predominantly high grade (86%), > or =5 cm (76%), and deep (81%). A minority of patients received adjuvant radiation (38%) and/or adjuvant chemotherapy (34%). Margin width was > or =10 mm (48%), 1-9 mm (40%), or 0 mm (12%). Margins > or =10 mm were less common for large (P = 0.009) or deep (P = 0.02) tumors. By multivariate analysis, independent factors for LRFI were tumor size (P = 0.04) and margin width (P = 0.03). Independent factors related to DMFI were tumor grade (P = 0.002), size (P = 0.007), and patient age (P = 0.02). Independent factors relating to OS were tumor grade (P = 0.001), size (P = 0.004), and depth (P = 0.03). Margins > or =10 mm independently predicted longer LRFI and are optimal for extremity STS resection. Adjuvant radiotherapy should be considered for all STS resected with margins <10 mm, and margin width should be considered when reporting and interpreting LR outcomes for these patients.

Multimodality Management of Locally Advanced Rectal Cancer

Despite the routine use of adjuvant chemoradiation for curatively resected stage II and III rectal cancer a significant percentage of patients ultimately fail locally and/or distally; this underscores the need for continued improvement in the efficacy of combined-modality therapy and quality of rectal cancer resection. The recognition of the significance of lateral or circumferential margins of resection has paralleled the widespread use of total mesorectal excision. In addition to facilitating negative margins of resection and local control, sharp mesorectal techniques also facilitate identification and preservation of pelvic autonomic nerves thereby greatly reducing the incidence of urinary and sexual dysfunction following radical resection. Lastly, restorative options can result in excellent bowel function in carefully selected patients undergoing a "very low" anterior resection. Efforts are currently directed at identifying the subset of locally advanced rectal cancer patients who may be adequately treated with a resection alone thereby avoiding the added morbidity of adjuvant radiation and chemotherapy.

The significance of a positive urethral margin at radical prostatectomy

The significance of a positive urethral margin at radical prostatectomy

Prognostic significance of the circumferential resection margin following total mesorectal excision for rectal cancer.

Knowledge of prognostic factors following resection of rectal cancer may be used in the selection of patients for adjuvant therapy. This study examined the prognostic impact of the circumferential resection margin on local recurrence, distant metastasis and survival rates. A national population-based rectal cancer registry included all 3319 new patients from November 1993 to August 1997. Some 686 patients underwent total mesorectal excision with a known circumferential margin. This shortest radial resection margin was measured in fixed specimens. None of the patients had adjuvant radiotherapy. Following potentially curative resection and after a median follow-up of 29 (range 14--60) months, the overall local recurrence rate was 7 per cent (46 of 686 patients): 22 per cent among patients with a positive resection margin and 5 per cent in those with a negative margin (margin greater than 1 mm). Forty per cent of patients with a positive margin developed distant metastasis, compared with 12 per cent of those with a negative margin. With decreasing circumferential margin there was an exponential increase in the rates of local recurrence, metastasis and death. The circumferential margin has a significant and major prognostic impact on the rates of local recurrence, distant metastasis and survival. Information on circumferential margin is important in the selection of patients for postoperative adjuvant therapy.

Significance of Margins of Excision on Breast Cancer Recurrence

Significance of Margins of Excision on Breast Cancer Recurrence

Significance of margins of excision on breast cancer recurrence.

Randomized studies have established wide excision and radiation as an equal alternative to mastectomy in the treatment of breast cancer. The early studies mandated pathologically negative margins for those undergoing radiation. The absolute necessity of free margins is uncertain. We evaluated our experience and outcome with breast-conserving surgery and radiation in relation to margin status. Two hundred sixty patients underwent wide excision for breast-conserving therapy for breast cancer. Reexcision was performed in 149 patients. The initial margin status was correlated with the amount of residual found on reexcision and the effect on local failure. The incidence of residual disease on reexcision in patients with initial gross margin involvement, focal margin involvement, and free margins was 30%. Patients with multiple margin positivity had a 65% incidence of residual disease. Only 9% (14/149) of the reexcised patients had more than 3 mm of residual cancer. This was more likely, but not significant, in those with initial margin involvement (11/100 or 11%) than in those with free margins (3/49 or 6%, p= 0.49). The risk of subsequent local failure was 8% (12/143) in those with initial free margins and 5% (6/117) in those with initial margin involvement. Those who had any residual tumor on reexcision had a nonsignificant risk of local failure (13%) compared to those that had no residual on reexcision (4%). Positive margin on initial excision is only slightly more likely to predict for residual cancer than the finding of negative margins. Routine reexcision of patients with positive margins does not significantly increase the chance of local control in patients who receive breast irradiation.

Prognostic significance of positive surgical margins in patients with extraprostatic carcinoma after radical prostatectomy.

A significant number of prostate adenocarcinoma patients undergoing radical prostatectomy are found to have microscopic extraprostatic disease extension. A majority of these patients have focal extraprostatic extension limited to one or both sides of the prostate. In addition, positive surgical margins are a common pathologic finding in this patient subgroup. In the current study, the authors evaluated the impact of positive surgical margins as an independent predictive factor for prostate specific antigen (PSA) progression in patients with pT3a/b N0M0 carcinoma. The Mayo Clinic prostate cancer registry list provided 1202 patients with pT3a/b NO prostate carcinoma (no seminal vesicle or regional lymph node involvement) who underwent a radical prostatectomy between 1987-1995. To reduce confounding variables, patients who received preoperative therapy or adjuvant therapy were excluded, resulting in 842 patients who were eligible for analysis. A total of 354 patients (42%) had > or = 1 positive surgical margins whereas 488 patients (58%) demonstrated no margin involvement. The sites of margin positivity were as follows: apex (n = 163), base (n = 47), posterior prostate (n = 227), and anterior prostate (n = 11). A total of 111 patients had > or = 2 positive surgical margins. The 5-year survival free of clinical recurrence and/or biochemical failure (postoperative PSA level > 0.2 ng/mL) for patients with no positive surgical margins was 76% and was 65% for patients with 1 positive surgical margin (P = 0.0001). There was no significant difference in biochemical disease progression between patients with 1 versus those with > or = 2 surgical margins (65% vs. 62%). Multivariate analysis revealed that positive surgical margins were a significant predictor (P = 0.0017) of clinical disease recurrence and biochemical failure (relative risk, 1.55; 95% confidence interval, 1.18-2.04) after controlling for preoperative PSA, Gleason score, and DNA ploidy. In the current study, positive surgical margins were found to be a significant predictor of disease recurrence in patients with pT3a/b NO prostate carcinoma, a finding that is independent of PSA, Gleason score, and DNA ploidy. The benefit of adjuvant therapy in optimizing recurrence-free survival remains to be tested.

Pathological Parameters of Radical Prostatectomy for Clinical Stages T1c Versus T2 Prostate Adenocarcinoma: Decreased Pathological Stage and Increased Detection of Transition Zone Tumors

Studies of radical prostatectomy specimens have suggested that the majority of prostate specific antigen detected (clinical stage T1c) tumors are clinically significant. We compared tumor location and pathological parameters in the radical prostatectomy specimens of stages T1c versus T2 cases in a 3-year period. The percent of stage T1c disease represented a stable majority of patients undergoing treatment for clinically localized prostate cancer. From January 1, 1998 to December 31, 2000, 417 radical prostatectomies were performed at Vanderbilt University, including 246 for stage T1c and 108 for stage T2 disease. A total of 37 patients were excluded from study because of neoadjuvant antiandrogen treatment. Pathological parameters, including tumor location in the transition and/or peripheral zone, tumor Gleason grade, tumor stage, total tumor volume and surgical margins were compared in stages T1c and T2 cases, and in transition versus peripheral zone stage T1c tumors in completely embedded whole mount specimens. In contrast to stage T2 lesions, stage T1c tumors were of significantly lower Gleason score with a higher percent of Gleason score 5 and lower percent of Gleason score 6, 7 and 8 or greater. They also had a significantly smaller volume and lower pathological stage. Of stage T1c tumors 77% were organ confined versus 62% of stage T2 tumors. There was no statistically significant increase in clinically insignificant neoplasms in stages T1c versus T2 cases (13% versus 7%) when using a volume criterion of less than 0.2 cc but a statistically significant increase in clinically insignificant disease was observed using a volume criterion of less than 0.5 cc (22% versus 9%). Whereas none of the T2 tumors were located in the transition zone and 17% were located in the transition and peripheral zones, 14% of stage T1c lesions were exclusively in the transition zone, with another 17% in the transition and peripheral zones. Compared with peripheral zone tumors transition zone stage T1c tumors had a lower Gleason score with an increase in Gleason score 5 and lower percent of Gleason score 6, 7 and 8 or greater. Although transition zone stage T1c lesions were significantly larger than peripheral zone stage T1c lesions, they had a lower pathological stage with 94% versus 72% organ confined. Prostate specific antigen detected stage T1c tumors had a lower grade, stage and volume than stage T2 tumors during the same period. Lower tumor grade in stage T1c cases is due at least in part to the increased detection of Gleason pattern 2 containing transition zone tumors. Despite the larger size, T1c transition zone tumors appear to be more favorable with higher rates of organ confined and lower grade tumors. If such transition zone tumors prove to be biologically distinct, improved strategies to identify these lesions preoperatively may result in more conservative treatment recommendations.

Positive Surgical Margins After Radical Retropubic Prostatectomy: The Influence of Site and Number on Progression

We assessed the effect of location and number of positive margins on biochemical progression in patients after radical retropubic prostatectomy for prostate cancer. The incidence, location and number of positive surgical margins as well as recurrence and time to recurrence were evaluated in a consecutive series of 734 men who underwent radical retropubic prostatectomy for localized prostate cancer from 1992 through February 1999. Surgical margins were positive in 210 patients (29%), of whom 157 (75%) and 53 (25%) had 1 and more than 1 positive margin, respectively. Of the patients 53 (25%) with tumor at any inked margin had biochemical recurrence. We identified no significant association of a particular location with biochemical recurrence. Bladder neck location did not carry an increased risk of recurrence (hazard ratio 1.23, 95% confidence interval 0.54 to 2.80). However, these findings were made in a limited number of cases with positive bladder neck margins. Patients with more than 1 positive surgical margin were at increased risk for recurrence compared with those with a single positive surgical margin (hazard ratio 2.19, 95% confidence interval 1.11 to 4.32). In addition, prostate specific antigen greater than 20 ng./ml. and seminal vesicle invasion were significant predictors of progression. In patients with localized prostate cancer and positive surgical margins biochemical progression is not dictated by the specific location of a positive margin. However, multiple positive margins are associated with a significantly increased risk of biochemical recurrence. Longer followup and larger sample size are necessary to confirm these findings.

Analysis of the prognostic significance of microscopic margins in 2,084 localized primary adult soft tissue sarcomas.

To define the significance of positive microscopic resection margins in a large cohort treated for soft tissue sarcoma. The authors analyzed 2,084 patients with localized primary soft tissue sarcoma (all anatomic sites) treated from 1982 to 2000. Clinicopathologic variables studied included tumor site, size, depth, histologic type, grade, and resection margin status. Treatment other than resection was not analyzed. Study endpoints included local and distant recurrence-free and disease-specific survival rates, estimated by the Kaplan-Meier method. Univariate and multivariate analyses were performed using the log-rank test and the Cox proportional hazards model. Median follow-up was 50 months. After primary resection, 1,624 (78%) patients had negative and 460 (22%) had positive resection margins. Having positive margins nearly doubled the risk of local recurrence and increased the risk of distant recurrence and disease-related death. Seventy-two percent of patients with positive margins had no recurrence. Resection margin did not predict local control for retroperitoneal sarcomas or fibrosarcomas. Resection margin remained significantly associated with distant recurrence-free survival and disease-specific survival across all subsets after adjusting for other prognostic variables. The overall 5-year disease-specific survival rates for negative and positive margins were 83% and 75%. Positive microscopic resection margins significantly decrease the local recurrence-free survival rate for other-than-primary fibrosarcoma and retroperitoneal sarcomas, and independently predict distant recurrence-free survival rates and disease-specific survival rates for all patient subsets. Adjuvant therapy should be considered in the management of soft tissue sarcoma to increase local control. Because 72% of positive margins did not equate with inevitable local recurrence, considerable clinical judgment is required in considering additional treatment. Microscopic resection margins should be considered for inclusion in staging systems and treatment algorithms that address local recurrence.

Prognostic significance of intraprostatic positive margins in organ confined (PT2) prostate cancer

Prognostic significance of intraprostatic positive margins in organ confined (PT2) prostate cancer

PROGNOSTIC FACTORS FOR SURVIVAL OF PATIENTS WITH PATHOLOGICAL GLEASON SCORE 7 PROSTATE CANCER: DIFFERENCES IN OUTCOME BETWEEN PRIMARY GLEASON GRADES 3 AND 4

We evaluated differences in clinical and pathological outcomes between Gleason 3 + 4 and 4 + 3 prostate cancer. The radical prostatectomy whole mounted specimens from 263 men with pathological Gleason 7 tumors were identified. Gleason 3 + 4 and 4 + 3 tumors were compared in regard to pathological variables and outcome. Significance of clinical and pathological data on progression-free survival was analyzed. Of the tumors 34% had a primary Gleason grade of 4, and were more likely than those with primary grade 3 to have seminal vesicle involvement (34% versus 18%, p = 0.006), a higher pathological stage (pT3 55% versus 42%, N+ 13% versus 3%, 0.001), extraprostatic extension (58% versus 38%, 0.001) and higher median preoperative prostate specific antigen (PSA) (13.5 versus 9.0 ng./ml., respectively <0.001). Mean followup plus or minus standard deviation was 6.8 +/- 1.9 years. The overall 10-year crude, cancer specific and progression-free survival rates were 83%, 99% and 58%, respectively. Primary Gleason grade was significantly associated with progression-free (risk ratio 1.6, 95% confidence interval 1.08 to 2.5, p = 0.02) but not crude and cancer-specific survival. Univariately, primary Gleason grade 4 was associated with progression-free survival, as were percent Gleason 4, seminal vesicle invasion, lymph node involvement, pT stage, margin status, DNA ploidy, preoperative PSA, cancer volume and extent of extraprostatic extension. Multivariately, only preoperative PSA (p <0.001), seminal vesicle invasion (<0.001) and DNA ploidy (0.002) were associated with progression-free survival. Primary Gleason grade and percent Gleason 4 were not identified as independently associated with progression-free survival. In patients with Gleason 7 score prostate cancer primary Gleason grade 3 and 4 cancers are different in pathological parameters and prognosis. However, primary Gleason grade does not provide any additional information than other known prognostic factors, such as preoperative PSA, seminal vesicle invasion and DNA ploidy.

Conservative surgery in breast cancer. Significance of resection margins

We approached the issue of surgical margins in the conservative treatment of breast cancer by examining the literature germane to four precise questions: At what distance from the macroscopic margin of the tumour should the resection margin be? To what extent do histologically clear resection margins indicate complete local control of the disease? To what extent do histologically involved margins indicate persistence of disease? and Does the local recurrence rate correlate with the status of the resection margin?We propose categorizing margin involvement into five groups (absent, focal, minimal, moderate and extensive involvement) according to strict histological criteria, and assigning increasingly aggressive subsequent treatments according to the extent of any margin involvement.

The prognostic significance of the circumferential resection margin in rectal cancer

The prognostic significance of the circumferential resection margin in rectal cancer

The prognostic significance of the circumferential resection margin in rectal cancer

The prognostic significance of the circumferential resection margin in rectal cancer

Significance of a positive oesophageal margin in stomach cancer.

A positive oesophageal margin is frequently encountered in total and proximal gastrectomies. It is controversial as to whether a positive oesophageal margin in gastrectomy predisposes to anastomotic dehiscence and loco-regional recurrence. Its independent impact on survival has not been fully addressed. A retrospective review of 137 total and proximal gastrectomies for adenocarcinoma was undertaken. Independent prognostic factors were identified in a bivariate and Cox proportional hazards regression model. The prevalence of positive oesophageal margin was 18.2%. A positive oesophageal margin was not associated with increased anastomotic leak (8.0 vs 10.7%; P = 0.51), operative morbidity (32.0 vs 27.7%; P = 0.85) or 30-day mortality (8.0 vs 5.4%; P = 0.48) rates when compared with a negative margin. In addition, it did not predispose to anastomotic (13.0 vs 10.4%; P = 0.47) or regional (22.7 vs 24.5%; P = 0.51) recurrences. In the multivariate analysis the TNM stage and status of the oesophageal margin were the only independent prognostic factors for survival. A positive oesophageal margin is an independent poor prognostic factor for long-term survival in stomach cancer. All efforts should therefore be made to clear the oesophageal margin in total and proximal gastrectomies.