Publications (5)30.4 Total impact
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Article: Time-Dependent Trends in Lymph Node Yield and Impact on Adjuvant Therapy Decisions in Colon Cancer Surgery: An International Multi-Institutional Study.
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ABSTRACT: BACKGROUND: Lymph node yield (LNY) and accuracy of nodal assessment are critical to staging and treatment planning in colon cancer (CC). A nationally agreed upon 12-node minimum is a quality standard in CC. The impact of this quality measure on LNY and impact on therapeutic decisions are evaluated in two international, multi-center, prospective trials comprising a well-characterized cohort assembled over 8 years (2001-2009) with long-term follow-up. HYPOTHESIS: Quality adherence through increased LNY improves staging accuracy and impacts adjuvant therapy decisions. METHODS: Retrospective analysis of prospective data to assess time-dependent LNY, the dependent variable in multivariate linear regression analysis adjusted for age, gender, body-mass-index (BMI), tumor size/stage/grade, anatomic location and surgery date. RESULTS: Two-hundred-forty-five patients with non-metastatic CC, median age 70 years, BMI 26 kg/m(2), tumor size 4.0 cm, and LNY 17 nodes were studied. Seventy-two percent had T3 (70 %)/T4 (2 %) tumors. Adherence to the 12-node minimum was 70 %(2001-2002), 81 % (2003-2004), 90 % (2005-2006), 94 % (2007-2008). LNY significantly increased over time (Median LNY: 2001-2004 = 15 vs. 2005-2008 = 17; P < 0.001) on multivariate analysis controlling for tumor size (P < 0.001), and right-sided tumor location (P < 0.001). Adjuvant therapy administration and indication for chemotherapy according to LNY (<12 vs. 12 + LNs = 33 % vs. 39 %; P = 0.48) and time period (2001-2004 vs. 2005-2008 = 39 % vs. 37 %; P = 0.89) remained unchanged. CONCLUSIONS: Despite the independent predictors of nodal yield (tumor location and size), year of study still had a significant impact on nodal yield. Despite increased quality adherence and LNY over time, there appears to be a delayed impact on adjuvant therapy decisions once quality standard adherence takes effect.Annals of Surgical Oncology 07/2012; · 4.17 Impact Factor -
Article: Surgical quality and nodal ultrastaging is associated with long-term disease-free survival in early colorectal cancer: an analysis of 2 international multicenter prospective trials.
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ABSTRACT: The National Quality Forum has endorsed a minimum of 12 lymph node (LN) as a surrogate measure of quality in colorectal cancer (CRC). The prognostic value of ultrastaging hematoxylin and eosin (H&E) negative LNs (N0) using pan-cytokeratin immunohistochemistry (pan-CK-IHC) is unknown. To assess the effect on survival of surgical quality and focused pathologic analysis. Between 2001 and 2007, 253 evaluable patients with resectable CRC were enrolled. Multiple sectioning and pan-CK-IHC were performed on N0 LNs (American Joint Commission on Cancer Stage II). Follow-up was performed at 6-month intervals with a 4-year disease-free survival (DFS) primary end-point. There were 253 patients, 177 N0 and 76 N1/N2 patients, staged conventionally. Thirty-six (20%) N0 patients were upstaged using ultrastaging (N0-->N0i+ [n = 27] and N0-->N1mi [n = 9]). At a mean follow-up of 3.4 +/- 1.6 years, 38 (15%) have recurred. Only 3% (3/108) of patients with > or =12 LNs, negative by H&E and pan-CK-IHC (N0i-), compared with 18% (6/33) with <12 LNs/N0i- (6/33; P = 0.0015) have recurred. Four-year DFS differed significantly according to surgical quality (<12 vs. > or =12 LNs) among Stage II patients only (DFS, <12 vs. > or =12 LNs: Stage I, 90.5% vs. 97.7%, P = 0.22; Stage II, 67.5% vs. 94.7%, P = 0.0036; Stage III, 61% vs. 61%, P = 0.61). This represents the first prospective report demonstrating that both surgical quality and nodal ultrastaging impacts survival in Stage II CRC. Patients with Stage II CRC having > or =12 LNs negative for micrometastases (N0i-) are likely cured by surgery alone. Both surgical and pathologic quality measures are imperative in early CRC to improve patient selection for adjuvant chemotherapy.Annals of surgery 09/2010; 252(3):467-74; discussion 474-6. · 7.90 Impact Factor -
Article: Predictors of occult nodal metastasis in colon cancer: results from a prospective multicenter trial.
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ABSTRACT: The relationship between primary colon cancer and occult nodal metastases (OMs) detected by cytokeratin immunohistochemistry (CK-IHC) is unknown. We sought to investigate the correlation of clinicopathologic features of colon cancer with OMs and to identify predictors of OM. Patients with colon cancer from 5 tertiary referral cancer centers enrolled in a prospective trial of staging had standard pathologic analysis performed on all resected lymph nodes (using hematoxylin and eosin staining [H&E]). Nodes negative on H&E underwent CK-IHC to detect OMs, which were defined as micrometastases (N1mic) or isolated tumor cells (N0i+). Patients who were negative on both H&E and CK-IHC were defined as node negative (NN), and those positive on H&E were node positive (NP). The relationships between tumor characteristics and OMs were analyzed using the Kruskal-Wallis and the Fisher exact test. OMs were identified in 23.4% (25/107) of patients. No significant differences were found in demographics, tumor location, tumor size, and number of nodes examined between groups. Compared with the NN group, patients with OMs had more tumors that were T3/T4 (72% vs 57%; P < .001), had tumors of higher grade (28% vs 12%; P = .022), and had tumors with lymphovascular invasion (16% vs 3%; P < .001). Adverse primary pathologic colon cancer characteristics correlate with OMs. In patients with negative nodes on H&E and stage T3/T4 colon cancer, lymphovascular invasion, or high tumor grade, consideration should be given to performing CK-IHC. The detection of OMs in this subset may influence decisions regarding adjuvant chemotherapy and risk stratification.Surgery 03/2010; 147(3):352-7. · 3.10 Impact Factor -
Article: Prognostic relevance of occult nodal micrometastases and circulating tumor cells in colorectal cancer in a prospective multicenter trial.
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ABSTRACT: Nodal micrometastasis and circulating tumor cells detected by multimarker quantitative real-time reverse transcription-PCR (qRT-PCR) may have prognostic importance in patients with colorectal cancer. Paraffin-embedded sentinel lymph nodes from 67 patients and blood from 34 of these patients were evaluated in a prospective multicenter trial of sentinel lymph node mapping in colorectal cancer. Sentinel lymph nodes were examined by H&E staining and cytokeratin immunohistochemistry. Sentinel lymph nodes and blood were examined by a four-marker qRT-PCR assay (c-MET, melanoma antigen gene-A3 family, beta1-->4-N-acetylgalactosaminyltransferase, and cytokeratin-20); qRT-PCR results were correlated with disease stage and outcome. In H&E-negative sentinel lymph node patients that recurred, cytokeratin immunohistochemistry and qRT-PCR detected metastasis in 30% and 60% of patients, respectively. Disease-free survival differed significantly by multimarker qRT-PCR upstaged sentinel lymph node (P = 0.014). qRT-PCR analysis of blood for circulating tumor cells correlated with overall survival (P = 0.040). Molecular assessment for micrometastasis in sentinel lymph node and blood specimens may help identify patients at high risk for recurrent colorectal cancer, who could benefit from adjuvant therapy.Clinical Cancer Research 11/2008; 14(22):7391-6. · 7.74 Impact Factor -
Article: Prognostic impact of micrometastases in colon cancer: interim results of a prospective multicenter trial.
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ABSTRACT: The 25% rate of recurrence after complete resection of stage II colon cancer (CC) suggests the presence of occult nodal metastases not identified by hematoxylin and eosin staining (H&E). Interim data from our ongoing prospective multicenter trial of sentinel node (SN) biopsy indicate a 29.6% rate of micrometastases (MM) identified by immunohistochemical staining (IHC) of H&E-negative SNs in CC. We hypothesized that these MM have prognostic importance. Between March 2001 and August 2006, 152 patients with resectable colorectal cancer were enrolled in the trial. IHC and quantitative RT-PCR (qRT) assay were performed on H&E-negative SNs. Results were correlated with disease-free survival. The sensitivity of lymphatic mapping was significantly better in CC (75%) than rectal cancer (36%), P<0.05. Of 92 node-negative CC patients 7 (8%) were upstaged to N1 and 18 (22%) had IHC MM. Four patients negative by H&E and IHC were positive by qRT. At a mean follow-up of 25 months, 15 patients had died from noncancer-related causes, 12 had developed recurrence, 5 had died of CC (2 with macrometastases, 3 with MM), and 7 were alive with disease. The 12 recurrences included 4 patients with SN macrometastases and 6 with SN MM (2 by IHC, 4 by qRT). One of the 2 SN-negative recurrences had other positive lymph nodes by H&E. All patients with CC recurrences had a positive SN by either H&E/IHC or qRT. No CC patient with a negative SN by H&E and qRT has recurred (P=0.002). This is the first prospective evaluation of the prognostic impact of MM in colorectal cancer. These results indicate that the detection of MM may be clinically relevant in CC and may improve the selection of patients for adjuvant systemic chemotherapy. Patients with CC who are node negative by cumulative detection methods (H&E/IHC and qRT) are likely to be cured by surgery alone.Annals of Surgery 10/2007; 246(4):568-75; discussion 575-7. · 7.49 Impact Factor
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