Presence Of Positive Margins Research Articles

Role of resection margins in patients treated with breast conservation surgery

After breast conservation therapy (BCT), margin status is routinely evaluated to select patients who need reexcision. The aim of this study was to investigate how margin status and other clinicopathologic factors correlate with the presence of residual tumor at reexcision. A series of 431 breast cancer patients who underwent BCT followed by reexcision were considered because they had positive or close (< or =3 mm) margins. At univariate and multivariate analysis the frequency of residual tumor in the reexcision specimens was associated with the status and width of resection margins and with a series of other clinicopathologic factors. Of the 382 evaluable patients, 253 had positive and 129 close margins. Residual tumor was found at reexcision in 51.8% positive-margin patients and 34.1% close-margin patients (P = .001). In the latter group tumor-margin distance (range, 0.08 to 3 mm) was not associated with the incidence of residual tumor (P = .134). On univariate analysis age < or =45 years (P = .006), intraductal histotype (P = .005), size > 2 cm (P = .010), positive axillary nodes (P = .031), and timing of reexcision (P = .044) were significantly associated with a higher frequency of residual tumor. All these factors, except tumor size, maintained a significant predictive value on multivariate analysis. In the presence of positive margins, relevant residual disease cannot be ruled out and further surgery is indicated. Close margins do not mandate reexcision because they may indicate either that the tumor has been radically excised or the presence of residual foci of a multifocal tumor, which are usually effectively treated by radiotherapy.

Ipsilateral breast tumor reappearance in patients treated with conservative surgery after primary chemotherapy. The role of surgical margins on outcome

To evaluate the ipsilateral breast tumor reappearance (IBTR) rate after breast conservative surgery (BCS) following primary chemotherapy (PC) and to assess whether positive margins affects IBTR rate and overall survival (OS). Three hundred nine women candidates for mastectomy received PC before surgery. One hundred ninety-five patients (63.1%) underwent BCS and 114 patients (36.9%) a modified radical mastectomy. After a median follow-up of 41 months (range 7-90), 13 patients of the 195 treated with BCS had an IBTR (6.7%), 6 patients had a regional relapse (3.1%), 28 women had distant metastases (14.4%). Twenty-three patients died of breast cancer (11.8%). Twenty-four patients treated with BCS had positive margins (12.3%). At 3 years, the crude cumulative incidence of local recurrence was 4.7% in women with negative margins, and 13.3% in women with positive margins (P=0.05). Cumulative incidence of distant metastases was similar in patients with positive and negative margins (P=0.16) and there was no significant difference in terms of OS according to the margin status (P=0.577). BCS after PC has an acceptable rate of IBTR. After a short follow-up, the presence of positive margins does not affect OS.

Adjuvant Therapy in Patients With Resected Poor-Risk Head and Neck Cancer

In patients with locally or regionally advanced head and neck carcinomas, postoperative radiotherapy has historically been the adjuvant therapy applied for patients with prognostically worrisome pathologic features. Any improvement in therapeutic index achieved by adding cytotoxic agents to postoperative radiotherapy remained controversial. However, two recent randomized trials, conducted in parallel in Europe and the United States, produced level I evidence regarding improved efficacy in this setting for the concurrent administration of chemotherapy and radiotherapy. High-dose cisplatin and irradiation can now be considered the standard therapeutic approach for resected poor-risk disease. The presence of positive margins and/or nodal extracapsular spread in the surgical specimens are the subgroups that appear to benefit in the most significant way from the addition of chemotherapy to radiation. Many questions regarding the optimization of adjuvant treatments still remain unanswered, especially with respect to improvement of patient compliance, integration of novel drugs targeting both locoregional and systemic control, and modulation of treatment intensity according to risk levels.

Facteurs pronostiques après résection pour cholangiocarcinome hilaire

Aims To evaluate short and long-term results in 23 patients resected for hilar cholangiocarcinoma. Methods Between January 2001 and December 2003, 23 patients with hilar cholangiocarcinoma were resected and considered for retrospective analysis. Univariate and multivariate analysis were performed on several clinicopathological variables in order to evaluate the short-term results. Median follow-up was 11 months (interquartile range 2–20 months). Results A major liver resection was performed in 19 out of 23 patients (82%): a right hepatectomy extended to segment 4 in 5 patients and a left hepatectomy in 14 patients. Resection of the caudate lobe was performed in 7 patients (30%). No hospital mortality occurred. Overall morbidity rate was 43%. The 1-year survival rate was 63.2% with a median survival of 19 months. Tumor recurrence appeared in 12 patients (52%). Low preoperative albumin level ( P = 0.006), presence of positive resection margin ( P = 0.03) and T-stage ( P = 0.02) were found to be related to a worse median survival. On multivariate analysis, only the preoperative albumin level and the presence of positive margin were confirmed as independent prognostic factors. Conclusion Aggressive surgical approach remains the only potentially curative therapy for the hilar cholangiocarcinoma. Low preoperative albumin level, presence of positive resection margin and T-stage resulted as factors influencing the prognosis after resection.

Management and Outcome of Patients With Malignant Salivary Gland Tumors

Refined imaging technology, the use of external beam radiation, neutron beam therapy, and chemotherapy, has altered management strategies for patients with salivary gland malignancies during the past 2 decades. Although treatment remains primarily surgical, optimal therapeutic regimens have yet to be fully realized. The purpose of this investigation is to report our experience with the management of patients with a variety of malignant salivary gland neoplasms that were treated with various combinations of surgery, radiation, and chemotherapy and to review treatment outcome in an effort to identify predictors of survival and locoregional control. The records of all patients with malignant salivary gland tumors presenting for treatment at our institution between 1992 and 2002 were retrospectively reviewed. Variables were collected and outcome measures were defined in terms of overall survival, disease-free survival, and locoregional control. Descriptive statistics were compiled and statistically evaluated. Survival was described using the Kaplan-Meier method. Prognostic factors were assessed using the Cox proportional hazards model. Clinical and reconstructive factors were reviewed. Eighty-five patients (35 males and 50 females) ranging in age from 16 to 89 years (mean, 58.6 years) met the criteria for inclusion in the study. The majority of tumors were located in the parotid gland (n = 42), with a significant minority located in the minor salivary glands (n = 29), followed by the submandibular gland (n = 8) and the sublingual gland (n = 6). Mucoepidermoid carcinoma was the most common neoplasm (n = 40). More than half of the patients presented in early-stage disease (stage I = 36, stage II = 17, stage III = 8, stage IV = 25). All patients were treated with surgery as the primary modality. Neck dissection was performed in 29% of patients, and more than half (56%) were treated with adjuvant external beam radiation therapy to a dose of 50 to 70 Gy. Patients were, in general, immediately reconstructed at the time of ablation using composite free tissue transfer when appropriate, local/regional rotational flaps, or maxillary obturators. The disease-free survival rate and locoregional control rate at 5 years were 77% and 86%, respectively. Stage (P = .0017), grade (P = .00044), cervical lymph node metastasis (P = .03), and age (P = .01) proved to make a statistically significant contribution when describing outcome. Neither site (P = .5), the presence of positive margins (P = .3), nor perineural invasion (P = .7) had a significant impact on survival. The treatment of salivary gland malignancies remains primarily surgical, although adjunctive radiotherapy may play an important role in those patients with advanced-stage disease. This study confirms the contributions of stage, grade, age, and cervical metastasis for describing survival. The benefits of combined modality therapy awaits prospective clinical trials.

Benign positive margins after radical prostatectomy means a poor prognosis—pro

Positive cancer margins occur in 11% to 46% of patients after radical prostatectomy. It is generally agreed that the presence of positive margins is a poor prognostic sign, with biochemical or clinical recurrence noted in as many as 63% of patients within 5 years postoperatively. Recently, with the rising incidence of biochemical failure postoperatively, the concept that prostate-specific antigen (PSA) recurrence after radical prostatectomy may not only be due to the three well-established sources (ie, positive surgical margins, metastatic disease, and/or local cancer recurrence), but also to the presence of benign prostatic glands in the surgical margin of the radical prostatectomy specimen has been proposed.

Cyclin A and Ki-67 expression as predictors for locoregional recurrence and outcome in laryngeal cancer patients treated with surgery and postoperative radiotherapy

Purpose To investigate the association between the cancer cell proliferation fraction and the risk of recurrence in laryngeal cancer patients treated without systemic therapy. Methods and materials Paraffin-embedded tumor samples from 90 laryngeal cancer patients were stained for cyclin A and the Ki-67 antigen by immunohistochemistry. The patients were treated with partial or total laryngectomy followed by postoperative radiotherapy to a total dose of 50 Gy or greater. The median follow-up time was 91 months (minimum 48 months). Results High cyclin A expression (>19% positive cancer cell nuclei, the highest tertile) was associated with a high rate of locoregional tumor recurrence and unfavorable disease-free and overall survival as compared with cases with a lower expression ( p = 0.025, 0.032, and 0.042, respectively). In a multivariate analysis, high cyclin A expression was an independent predictor of poor disease-free survival (RR 2.4, 95% CI 1.2–4.9, p = 0.013) and overall survival (RR 2.1, 1.2–3.6, p = 0.012), together with a poor Karnofsky's performance status and the presence of positive margins at surgery. Ki-67 expression was not an independent predictor of survival, but cancers with high Ki-67 expression (>34% nuclei positive, the highest tertile) recurred more frequently locoregionally when treated with split-course radiotherapy than when treated with a continuous course of therapy ( p = 0.035), whereas the presence of a planned split did not influence the frequency of locoregional recurrences when Ki-67 expression was lower ( p = 0.93). Conclusion Cancer cell cyclin A expression is a novel predictive factor for outcome in laryngeal cancer treated with surgery and postoperative radiotherapy. Planned gaps in the radiotherapy course are deleterious in patients with a high proliferative fraction, and immunostaining for the Ki-67 antigen may be useful in identification of such patients.

Radical prostatectomy with bladder neck preservation: impact of a positive margin.

Bladder neck preservation during radical prostatectomy has been correlated with improved continence. However, the hazard of a positive margin at this specific site has discouraged many urologists. We evaluated if preservation of the bladder neck at the time of radical prostatectomy jeopardizes surgical cancer control with consequent deleterious outcomes. 675 consecutive patients underwent radical prostatectomy (RP) by a single surgeon (J.E.P.) at Wayne State University during the 1990s decade. The bladder neck was preserved. Margin-positivity was categorized by location and number. Preoperative, pathological and disease status data was prospectively collected into the Karmanos Cancer Institute multidisciplinary prostate cancer database. Analysis was performed on 555 patients who had RP as monotherapy. Positive margins were found in 178 (32%) of these patients. Correlation between specimen Gleason score, prostatic specific antigen (PSA) and margin status, was encountered (p=0.001). Apical and bladder neck margin-positivity was detected in 104/555 (19%) and 13/555 (2%), respectively. Of those specimens with a positive margin at the bladder neck eight had Gleason score > or =7, three had seminal vesicle invasion and two nodal disease. Only two patients had a positive bladder neck margin as the sole adverse pathological feature. Significant independent predictors of survival included the Gleason score, PSA, pathological stage and presence of positive margins in more than one location. Anatomical preservation of the bladder neck does not increase the percentage of positive margins at this anatomical location and does not compromise disease-free survival.

Surgical management of isolated retroperitoneal recurrences of colorectal carcinoma.

Isolated locoregional disease accounts for approximately 20 percent of recurrences after treatment for colorectal cancer. It has been suggested that complete resection of these recurrences can result in increased survival. The value of surgery for isolated retroperitoneal recurrences has not been well defined. We have sought to characterize outcome and survival in patients undergoing resection for isolated retroperitoneal recurrences of colorectal cancer. From a prospective database, 25 patients were identified as having undergone surgical exploration with curative intent for isolated retroperitoneal recurrences of colorectal cancer between 1988 and 1999. Variables studied included age, gender, location and size of the tumor, extent of resection, disease-free interval, and morbidity and mortality. Statistical analyses were performed using the log-rank test and Kaplan-Meier estimates, with overall survival as the primary end point. The study population consisted of 25 patients (13 males), with a median age of 55 years and a median follow-up of 29 (range, 1-151) months. The median time to first retroperitoneal recurrence was 23 (range, 3-72) months. Twenty patients underwent resection, whereas five patients were deemed unresectable at the time of operation. The median survival in patients who underwent resection patients was 31 months compared with 3 months in those patients who did not undergo resection (P = 0.0001). Analysis of the entire group demonstrated a disease-free interval of greater than 24 months to be a positive predictor of outcome (median survival, 30 vs. 48 months; P = 0.02). For patients undergoing resection, the presence of positive margins (P = 0.01) and tumor size >or=5 cm (P = 0.008) predicted a worse prognosis. In patients who underwent resection, the two-year and five-year overall survival rates were 60 and 15 percent, respectively. Patients with isolated retroperitoneal recurrences of colorectal cancer generally have a poor prognosis. However, a longer disease-free interval, complete negative-margin resection, and smaller tumor size are associated with long-term survival in selected patients.

Factores que afectan el control local, regional y supervivencia en carcinomas de lengua móvil y suelo de boca

Aretrospective study of 142 patients that had previous surgery for carcinoma of the tongue or floor of mouth looking into the factors that affect significantly the evolution of our patients and in which circumstances we could benefit from new therapeutic techniques. Cause specific survival at 3 and 5 years was 63.4% and 56.9% respectively. Recurrences were found locally in 32 patients (22.5%), regional in 32 (22.5%) and metastasic in 11 (7.4%). T staging had no did impact on local recurrence, but the presence of positive margins (p=0.0323). Regional control for N0/N1 was 85% (90/106) versus 55.5% (20/36) for N2/N3 (p=0.001). Regional control by N staging was 84.5% (73/86) for N0, 85% (17/20) for N1, 57% (30/35) for N2 and 0% for N3 (0/1). Both, N staging and number of positive nodes had a significant impact in specific survival. Positive margins and the presence of positive nodes have the greatest impact on survival and regional control. Adjuvant postoperative radiotherapy did not increase survival, but not prospective random selection was performed. To evaluate this.

Effect of microscopic resection line disease on gastric cancer survival

To study the effect of residual microscopic resection line disease in gastric cancer, we compared 47 patients with positive margins to 572 patients who underwent R0 resections using a multivariate analysis of factors affecting outcome. Although the presence of positive margins was a significant and independent predictor of outcome for the entire group (N = 619), this factor lost significance in patients who had undergone D2 or D3 lymph node dissections (N = 466). Subset analysis within the D2/D3 group determined that this finding was limited mainly to those patients with >5 positive nodes (N = 189). The survival of patients who had ≤5 positive nodes (N = 277) was significantly worsened by a microscopically involved margin. Supporting this observation, intraoperative reexcision of microscopic disease based on frozen section analysis resulted in a significant improvement in overall survival in patients with ≤5 positive nodes but not in those with >5 positive nodes. We conclude that the significance of a positive microscopic margin in gastric cancer is dependent on the extent of disease. This factor is not predictive of outcome in patients who have undergone complete gross resection and have pathologically proved advanced nodal disease. Thus the goal in these cases should be an R0 resection when feasible but with the realization that the presence of ≥5 positive nodes (N2 disease according to the 1997 American Joint Committee on Cancer criteria) will mainly determine outcome and not microscopic residual cancer at the margin.

Effect of microscopic resection line disease on gastric cancer survival

Abstract To study the effect of residual microscopic resection line disease in gastric cancer, we compared 47 patients with positive margins to 572 patients who underwent R0 resections using a multivariate analysis of factors affecting outcome. Although the presence of positive margins was a significant and independent predictor of outcome for the entire group (N = 619), this factor lost significance in patients who had undergone D2 or D3 lymph node dissections (N = 466). Subset analysis within the D2/D3 group determined that this finding was limited mainly to those patients with >5 positive nodes (N = 189). The survival of patients who had ≤5 positive nodes (N = 277) was significantly worsened by a microscopically involved margin. Supporting this observation, intraoperative reexcision of microscopic disease based on frozen section analysis resulted in a significant improvement in overall survival in patients with ≤5 positive nodes but not in those with >5 positive nodes. We conclude that the significance of a positive microscopic margin in gastric cancer is dependent on the extent of disease. This factor is not predictive of outcome in patients who have undergone complete gross resection and have pathologically proved advanced nodal disease. Thus the goal in these cases should be an R0 resection when feasible but with the realization that the presence of ≥5 positive nodes (N2 disease according to the 1997 American Joint Committee on Cancer criteria) will mainly determine outcome and not microscopic residual cancer at the margin.

Prostate-specific antigen doubling times in patients who have failed radical prostatectomy: Correlation with histologic characteristics of the primary cancer

Objectives This study sought to characterize the postoperative prostate-specific antigen (PSA) doubling time and time to biochemical recurrence in patients who have failed radical prostatectomy. Methods Of 539 consecutive patients who underwent radical prostatectomy between 1984 and 1992, postoperative PSA levels in 80 initially became undetectable (less than 0.07 ng/mL) before eventually increasing, as evidenced by rising PSA levels above the residual cancer detection limit of the Tosoh AIA-600 immunoassay run in the ultrasensitive mode (ie, 0.07 ng/mL or higher). The PSA doubling time and time to biochemical recurrence were calculated for each of the 80 patients and were correlated with the histopathologic variables from the operative specimen. Results Postoperative PSA doubling times were predicted by the extent of capsular penetration, percent Gleason grade 4 or 5, lymph node involvement, and tumor volume on univariate analysis and by capsular penetration, percent Gleason grade 4 or 5, lymph node involvement, and patient age on multivariate analysis. Times to recurrence were predicted by the presence of positive margins and percent Gleason grade 4 or 5 in both univariate and multivariate regression models. The PSA doubling time did not correlate with recurrence time. The median PSA doubling time for all patients was 284 days, and the median time to recurrence was 648 days. Conclusions These results demonstrate that PSA doubling time and recurrence time are indicative of different biologic characteristics of recurrent prostate cancer: Doubling time appears to represent the aggressiveness of the original prostate cancer, whereas time to recurrence reflects the extent of residual postoperative disease. This information should aid in the selection of men who need greater vigilance during postoperative surveillance.

Postoperative radiotherapy in carcinoma of the cervix: treatment results and prognostic factors

In order to assess the role of postoperative radiotherapy and prognostic factors, 126 patients who were treated with radiotherapy after surgery for clinical early-stage carcinoma of the cervix were reviewed. All patients received external pelvic radiotherapy and 37 patients were treated with additional vaginal cuff irradiation. The 5-year overall survival, disease-free survival and locoregional control rates were 71.1,69.9 and 78.1%, respectively. The 5-year disease-free survival rates were 40% for grade 3 vs. 75.4% for grade 1 tumours ( p = 0.05), 76.5% for pathological stage IB versus 54.1% for pathological stage IIA ( p = 0.04), 36.6% for node-positive patients versus 82.5% for node-negative patients ( p = 0.0017), 54% for full thickness cervical invasion versus 100% superficial cervical invasion ( p = 0.01), 34.8% for positive margins versus 78.1 for negative margins ( p < 0.0001). After a multivariate analysis, tumour grade ( p = 0.026) and presence of positive margins ( p = 0.006) were found to independently influence the outcome. Grade II and III complication rate was 5.5% in all patients. In conclusion, postoperative radiotherapy should be used in patients treated with simple hysterectomy as well as those treated with radical hysterectomy with unfavorable pathological findings.

Pylorus-preserving pancreatoduodenectomy. Is it an adequate cancer operation.

To assess the adequacy of pylorus-preserving pancreatoduodenectomy (PPPD) as a definitive surgical treatment for primary malignant diseases of the periampullary region. Retrospective review of the clinical records of patients undergoing PPPD for malignant diseases of the periampullary region. Median and 5-year actuarial survival by type and stage of cancer were determined. Survival data from this study were compared with those of patients undergoing a conventional Whipple operation. Lahey Clinic, Burlington, Mass. One hundred six patients undergoing PPPD for primary malignant disease of the periampullary region between November 1979 and June 1992. Pylorus-preserving pancreatoduodenectomy was performed with curative intent in the 106 patients. Ninety-five patients underwent proximal pancreatectomy; 11 patients, total pancreatectomy. Resection of the portal vein was performed in 10 patients. Long-term survival following PPPD was analyzed with respect to the type and stage of cancer. Median follow-up was 30 months (range, 6 to 156 months). Five-year actuarial survival rates were 45.4% for patients with ampullary adenocarcinoma; 6.6%, with pancreatic ductal adenocarcinoma; 33.3%, with distal bile duct adenocarcinoma; 75%, with pancreatic islet cell adenocarcinoma; and 0%, with pancreatic cystadenocarcinoma. An early cancer stage was associated with more favorable survival for ampullary and distal bile duct adenocarcinomas. For pancreatic ductal adenocarcinoma only, tumors less than 2 cm were associated with better survival. Duodenal resection margins were free of disease in all patients, while peripancreatic and retroperitoneal extension of the tumor was found in 20%. For patients with periampullary malignant disease, long-term survival following PPPD is similar to that following a conventional Whipple operation. The potential benefits of hemigastrectomy with perigastric lymphadenectomy are frequently obviated by the presence of positive margins and lymph nodes elsewhere, ie, in the retroperitoneum. We advocate PPPD as the procedure of choice for locally resectable malignant disease of the periampullary region, provided the duodenal margin is viable and tumor free.

Implications of tumour in resection margins following surgical treatment of squamous cell carcinoma of the head and neck.

Presence of tumour at the resection margin following primary surgical treatment for squamous cell carcinoma of the head and neck is thought to adversely affect prognosis. To confirm this we performed a review of 478 patients treated by primary surgery for squamous cell carcinoma of the head and neck and sub-divided them into those exhibiting positive margins and those with negative margins following resection. Uni-variate and multi-variate statistical methods were used to analyse survival figures and a variety of parameters associated with the presence of positive resection margins. We found 5-year survival was decreased if resection margins were found to be positive (P < 0.025). The presence of positive resection margins was also significantly associated with time to tumour recurrence (P < 0.001) and survival with nodal recurrence (P < 0.001). Other factors which were significantly associated with survival using Cox's multi-variate analysis were site of tumour (P < 0.005), nodal extracapsular rupture (P < 0.05), histology (P < 0.05) and pathological T-stage (P < 0.05). Uni-variate analysis revealed no significant associations between the presence of positive margins and the patient's age, sex, tumour site, degree of tumour differentiation, and nodal status, though using multiple logistic regression, the general condition of the patient (P < 0.01) and the tumour site P < 0.05) were significantly related. The results support the concept that every effort should be made to obtain negative resection margins when undertaking primary ablative surgery for squamous cell carcinoma of the head and neck.