Biomedical subjects

David Wiese

Publications and source records attributed to David Wiese.

12 recordsLinked to original sources

PubMed2006

Prospective multicenter trial of staging adequacy in colon cancer: preliminary results.

HYPOTHESIS: Lymph node evaluation is an important prognostic factor in colorectal cancer (CRC). A 25% recurrence rate in patients with node-negative CRC suggests that current staging practices are inadequate. Focused analysis of the sentinel node (SN) by multiple sectioning and immunohistochemistry improves staging accuracy. DESIGN: Prospective phase 2 multicenter trial. SETTING: Tertiary referral cancer centers. PATIENTS: Between March 2001 and June 2005, 132 patients were enrolled with clinical stage I and II CRC in a prospective multicenter trial (R01-CA90484). INTERVENTION: During a standard oncologic resection, lymphatic mapping was performed and the SN identified either by the surgeon or the pathologist. Hematoxylin-eosin staining was performed on all lymph nodes and immunohistochemistry, on lymph nodes negative by hematoxylin-eosin staining. MAIN OUTCOME MEASURES: Micrometastases greater than 0.2 mm but less than 2 mm and isolated tumor cells less than 0.2 mm were defined according to the sixth edition of the American Joint Committee on Cancer Cancer Staging Manual. RESULTS: The 63 men and 69 women had a median age of 74 years. Sixty-eight patients (52%) underwent a right hemicolectomy; 3 (2.3%), a transverse colectomy; 9 (7%), a left colectomy; 15 (11%), a sigmoid colectomy; 34 (26%), a low anterior resection; 1 (1%), an abdominal perineal resection; and 2 (2%), a total colectomy. Of the 111 evaluable primary tumors, 19 (17%) were T1 lesions; 17 (15%), T2; 72 (65%), T3; and 3 (2.7%), T4 tumors. Thirty-three patients (30%) were classified as stage I; 46 (41%), stage II, and 32 (29%), stage III. The SN was identified by the surgeon in 127 patients (96%) and by the pathologist in 5 patients (4%). The median number of SNs and total lymph nodes examined were 3 and 14.5, respectively. The sensitivity of lymphatic mapping and SN analysis was 88.2% and the false-negative rate, 7.4% (6/81). Of the 6 false-negative results, 4 were attributed to lymphatic channels obliterated by tumor. Upstaging occurred in 28 patients (23.6%). CONCLUSIONS: In a multicenter trial, ultrastaging of colon cancer is feasible and accurate. In stage II CRC, 24% of patients had nodal carcinoma cells not detected by conventional staging methods. Surgical technique (adequate lymph node retrieval) and focused pathological analysis may improve staging accuracy and the selection of patients for chemotherapy. The unnecessary toxicity and expense of chemotherapy may be avoided in those patients who are truly node negative.

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PubMed2006

A multicenter trial of sentinel lymph node mapping in colorectal cancer: prognostic implications for nodal staging and recurrence.

BACKGROUND: Sentinel lymph node (SLN) mapping (M) for staging in colorectal cancer (CRCa) remains controversial and needs to be validated. This study analyzes results of SLNM at a multi-institutional level for CRCa. METHODS: Group A patients underwent SLNM with 1 to 3 mL of 1% lymphazurin. First 1 to 4 blue lymph nodes were designated as SLNs and had focused analysis. Group B had standard resection and nodal staging. Patients with a minimum of 2 years of follow-up were analyzed for recurrence. RESULTS: Overall nodal metastasis were 50% for 500 group A patients versus 35% for 368 group B patients. In SLNM patients success, accuracy, sensitivity, and negative predictability values were 98%, 96%, 90%, and 93%, respectively. With a 2-year minimum follow-up, 153 group A patients had 7% recurrences compared with 25% in 162 group B patients. CONCLUSION: SLNM is highly feasible and accurate for staging CRCa with higher detection of nodal metastasis and lower recurrences.

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PubMed2005

Sentinel lymph node mapping in colon and rectal cancer: its impact on staging, limitations, and pitfalls.

Sentinel lymph node (SLN) mapping has been widely applied in the staging of solid neoplasms including colon and rectal cancer. Since the first reported feasibility study in 1997, there have been numerous publications validating SLN mapping as a highly accurate and powerful upstaging technique for colon and rectal cancer. In addition to refining the technical aspects of this procedure, these studies have investigated the use of other tracers and operative techniques, while determining the indications, limitations, and pitfalls of SLN mapping in patients with colorectal cancers. This chapter reviews the rationale for performing SLN mapping for the accurate staging of colon and rectal cancers, and provides a brief review of the historical background of the development of the procedure. Landmark publications, which have contributed to the current status of the technique, are discussed. We will focus on the technical details of the procedure, and on the pathological evaluation of the specimen and the SLNs. The various tracers and techniques of SLN mapping in colon and rectal cancer will be discussed. We have performed SLN mapping in more than 240 consecutive patients over the past 7 years. The success rates for identifying at least one SLN for colon and rectal cancer were 100% and 90.6%, respectively. The accuracy rates were 95.8% and 100%, respectively. In terms of upstaging, 32.3% of colon cancer patients with nodal metastases and 16.7% of rectal patients with nodal metastases were upstaged by the detection of micrometastases found in the SLNs only. Finally, we will also discuss the current role as well as the future research directions for SLN mapping in colon and rectal cancer.

Colonic Neoplasms↗

PubMed2004

1% lymphazurin vs 10% fluorescein for sentinel node mapping in colorectal tumors.

HYPOTHESIS: Ten percent fluorescein may be successfully used as an alternative to 1% Lymphazurin (1% isosulfan blue; US Surgical Corp, North Haven, Conn) in sentinel lymph node (SLN) mapping for the accurate staging of colorectal tumors. DESIGN: Review of prospectively gathered data. SETTING: University-affiliated regional medical center. PATIENTS: Sentinel lymph node mapping was performed in 120 consecutive patients with colorectal malignancies. INTERVENTIONS: The first 1 to 4 blue nodes detected within 5 minutes were designated as Lymphazurin-detected SLNs. The first 1 to 4 fluorescent nodes seen under the Wood light were designated as fluorescein-detected SLNs. Multilevel serial sections for hematoxylin-eosin and immunohistochemistry studies for cytokeratin were performed on all SLNs. MAIN OUTCOME MEASURES: Successful mapping, accuracy, skip metastasis, adverse reactions, occult micrometastases detection, and cost. RESULTS: Mapping was successful using Lymphazurin in 99% of the patients vs 97% of the patients using fluorescein (P =.89). The accuracy of predicting nodal metastases with each tracer was 95.8% vs 93.1%, respectively (P =.82). The skip metastases rate was 4.2% for Lymphazurin vs 6.9% for fluorescein (P =.37). The 5 patients in whom nodal disease was only identified as occult micrometastasis in the SLNs had a total of 5 SLNs, all of which were identified by both tracers. No adverse reactions occurred. The cost for Lymphazurin was $99.00, while the cost for fluorescein was $2.10. CONCLUSIONS: With the exception of cost, there were no statistically significant differences between the 2 dyes. While easy availability and lower cost remain distinct advantages of fluorescein, Lymphazurin remains the gold standard. In patients with known hypersensitivity to Lymphazurin and when availability and cost are an issue, fluorescein may be used effectively for SLN mapping in colorectal tumors.

Adult↗

PubMed2004

Historical review of lymphatic mapping in gastrointestinal malignancies.

The advent of sentinel lymph node mapping (SLNM) has had a profound impact on the surgical management of breast cancer and melanoma over the past decade. However, SLNM in gastrointestinal malignancies is still in its infancy. The role of SLNM in gastrointestinal malignancies is to increase staging accuracy and to reduce the understaging associated with standard surgical and pathological techniques. Numerous authors have described the successful use of SLNM in colon, rectal, gastric, esophageal, and anal canal malignancies, with a high degree of accuracy and upstaging by detailed pathological analysis of the sentinel nodes. Over the past 2 years, research and publications related to gastrointestinal lymphatic mapping have dramatically increased worldwide.

Colorectal Neoplasms↗

PubMed2004

Lymphazurin 1% versus 99mTc sulfur colloid for lymphatic mapping in colorectal tumors: a comparative analysis.

BACKGROUND: The combination of isosulfan blue (Lymphazurin) 1% and 99(m)Tc sulfur colloid (TSC) may improve the feasibility and accuracy of lymphatic mapping for colorectal cancer. METHODS: At laparotomy, 1 to 2 mL of isosulfan blue and 1 mCi of TSC were injected subserosally. Sentinel lymph node (SLN) designation was based on blue staining for isosulfan blue and increased radioactivity for TSC. Focused pathologic analysis of the SLNs and standard pathologic examination of the remaining specimen were performed. RESULTS: A total of 57 consecutive patients were studied (median age, 71 years; 27 men and 30 women). Mapping was successful in 100% of patients with isosulfan blue and in 89% with TSC (P =.47). Lymphatic mapping was accurate in 93% of patients with isosulfan blue versus 92% with TSC (P =.53). The combined accuracy was 95%. A total of 709 lymph nodes were found (12.4 per patient): 553 non-SLNs (5.6% nodal positivity) versus 156 SLNs (16.7% nodal positivity; P <.0001). Isosulfan blue detected 152 SLNs, TSC detected 100, and both modalities detected 96. Of the SLNs detected by isosulfan blue only, 10.7% had nodal metastases, whereas 19.8% of SLNs detected with both modalities had nodal metastases (P =.028). Nodal disease was detected in 41% of patients with invasive carcinoma. Metastases were detected only in the SLNs in 26% and only by micrometastases in 11% of these patients. CONCLUSIONS: These data confirm the efficacy of isosulfan blue and TSC for SLN mapping in colorectal tumors. No significant difference with respect to feasibility or accuracy exists between isosulfan blue and TSC. The metastatic yield is significantly higher in SLNs identified by both modalities compared with isosulfan blue only.

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PubMed2004

Comparative analysis of nodal upstaging between colon and rectal cancers by sentinel lymph node mapping: a prospective trial.

PURPOSE: Sentinel lymph node mapping accurately predicts nodal status in > 90 percent of melanoma and breast and colorectal cancers. However, because of anatomic differences, sentinel lymph node mapping of rectal cancers has been considered inaccurate and difficult relative to colon. A prospective study was undertaken to identify differences in sentinel lymph node mapping between patients with colon cancer and those with rectal cancer. METHODS: At operation 1 to 3 ml of 1 percent isosulfan blue dye was injected subserosally around colon cancers. The first to fourth blue-staining nodes seen within ten minutes of injection were marked as sentinel lymph nodes. For cancer of the mid-rectum to low rectum, the dye was injected submucosally via rigid scope and spinal needle. The mesorectum was dissected ex vivo to identify blue nodes nearest the tumor as sentinel lymph nodes. Multilevel microsections of sentinel lymph nodes were stained with hematoxylin and eosin and immunostained for cytokeratin, and standard examination of the entire specimen was performed. RESULTS: There were 407 consecutive patients (336 with colon and 71 rectum). The sentinel lymph nodes were identified in 99.1 percent of colon and 91.5 percent of rectal patients (P < 0.0001). Skip metastases were found in 3.6 percent of colon vs. 2.8 percent of rectal patients (P = 0.16). Occult micrometastases were found in 13.4 percent of colon vs. 7.0 percent of rectal patients (P = 0.24). Except for success rates, no other parameters were statistically different between colon and rectum. Lower success in sentinel lymph node identification in rectal cancer may have been related to neoadjuvant chemoradiation received in all six of the patients with sentinel lymph node mapping failures. CONCLUSION: Despite higher success rates in sentinel lymph node identification for colon patients, sentinel lymph node mapping was highly successful (91.5 percent) in rectal patients. Nodal upstaging, skip metastases, and occult metastases were similar.

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PubMed2004

Sentinel lymph node mapping technique in colon cancer.

Current conventional surgical and pathological techniques substantially understage colon cancer. This is evidenced by the fact that a significant subset of patients who are stage I and II at the time of colectomy return with distant metastases and ultimately succumb to the disease within the next 5 years. The identification of more nodes within a specimen and the detailed analysis of lymph nodes with advanced pathological techniques such as immunohistochemistry and reverse-transcriptase polymerase chain reaction (RT-PCR) can improve the staging of colon cancer, but are also associated with tremendous financial, time, and labor constraints. Sentinel lymph node (SLN) mapping has provided an avenue of staging colon cancer with high success rates and accuracy rates, while maintaining cost- and time-effectiveness. The ability to reproduce these results is dependent on adherence to the technical details of the procedure, and thereby providing the pathologist with the true SLNs, upon which the advanced pathological studies can be applied. We report our experience of SLN mapping for colon tumors in 209 patients, elaborating on the materials used, technical details, pitfalls, and results of the procedure. Our results show a success rate of 100% (209/209) and an overall accuracy rate for predicting positive or negative metastatic disease of 96.2% (201/209). Nodal metastases were identified in 46.2% (85/184) of patients with invasive disease (stage T1 to T4). The SLN was the exclusive site of metastases in 38.8% (33/85) of these patients, and the nodal disease was detected only as micrometastases in 22.4% (19/85). The skip metastases rate (false negatives) was 9.4% (8/85). SLN mapping is a powerful tool for accurate staging of colon cancer with a high success rate. The upstaging associated with this procedure may reveal disease that might otherwise go undetected by conventional surgical and pathological methods. Those patients who are upstaged can then benefit from adjuvant chemotherapy, which has been shown to improve survival of colon cancer patients with nodal disease by at least 33%.

Colonic Neoplasms↗

PubMed2003

c-MET expression level in primary colon cancer: a predictor of tumor invasion and lymph node metastases.

PURPOSE: Both c-MET and vascular endothelial growth factor (VEGF)-C expression are important factors in primary carcinoma progression. We hypothesized that overexpression of c-MET and/or VEGF-C mRNA in primary colorectal cancer (CRC) can predict tumor invasion and regional metastasis. EXPERIMENTAL DESIGN: The level of c-MET and VEGF-C mRNA expression was assessed using a quantitative RT-RealTime PCR assay on early stage primary CRC tumors (n = 36). RESULTS: The c-MET mRNA copy number ranged from 1.18 x 10(2) to 1.11 x 10(6) copies (median 5.17 x 10(4)) per 250 ng of RNA from CRC specimens. c-MET mRNA copies in CRC specimens was significantly higher than that from normal colon mucosal epithelium (P = 0.0001). c-MET mRNA copies significantly correlated with the depth of invasion: T(1) versus T(2), P = 0.007; T(1) versus T(3)/T(4), P = 0.0001; T(1) versus T(2) versus T(3)/T(4), P = 0.0005; and T(1)/T(2) versus T(3)/T(4), P = 0.011. c-MET copy number in primary CRC of N(1)/N(2) staged patients was significantly higher than N(0) cases (P < 0.03). Expression levels of c-MET mRNA were verified with immunohistochemistry analysis of c-MET protein expression in CRC specimens and normal mucosal epithelium. The VEGF-C mRNA copies of primary CRC assessed ranged from 0 to 1.65 x 10(5) copies (median 580). Although VEGF-C mRNA copies in CRC primary tumors were significantly higher than normal colon mucosal epithelium (P = 0.0008), it did not correlate with any major clinicopathological parameters of CRC. CONCLUSIONS: This study indicates c-MET mRNA overexpression in primary CRC may be an important prognostic marker for early stage invasion and regional disease metastasis.

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PubMed2003

Differential expression of thymidylate synthase in colorectal tumors and matched lymph nodes: impact on adjuvant treatment.

Although the expression of thymidylate synthase (TS) in metastatic colorectal cancer (CRC) may be a better predictor of response to 5-fluorouracil chemotherapy than TS expression in primary CRC, this enzyme has not been well studied in tumor-draining regional lymph nodes. We retrospectively examined TS expression in 12 primary CRC lesions (pT3) and matched sentinel lymph nodes. Of the 8 primary tumors that were TS-positive, 50 per cent (4/8) had tumor-positive lymph nodes and 50 per cent (4/8) had tumor-negative nodes. Of the 4 primary tumors that were TS-negative, 75 per cent (3/4) had tumor-positive nodes and 25 per cent (1/4) had tumor-negative nodes [kappa = -0.1386, 95 per cent confidence interval: (-0.4820, 0.2048), P = 0.4284]. Of the 8 TS-positive primaries, 25 per cent (2/8) had TS-positive nodes and 75 per cent (6/8) had TS-negative nodes. Of the 4 TS-negative primaries, 50 per cent (2/4) had TS-positive nodes and 50 per cent (2/4) had TS-negative nodes [kappa = -0.0131, 95 per cent confidence interval: (-0.2958, 0.2696), P = 0.9274]. Two of the three TS-negative primaries that had metastasized to regional lymph nodes were associated with TS-positive lymph nodes. Our findings indicate that expression of TS by a primary CRC does not correlate with nodal metastases or nodal TS expression. Nodal expression of TS may be important in predicting response to 5-fluorouracil when a primary CRC is TS-negative.

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PubMed2002

The use of molecular profiling of early colorectal cancer to predict micrometastases.

BACKGROUND: Approximately one third of node-negative colorectal cancers (CRCs) recur, suggesting the failure to detect occult disease. Lymphatic mapping followed by focused analysis of the sentinel node is highly accurate in identifying micrometastases. HYPOTHESIS: Because aberrant genetic changes occur early in tumor progression and are associated with lymphatic metastases, we hypothesized that the molecular profiling of specific tumor markers in the primary tumor might predict that tumor's metastatic potential. DESIGN: A prospective patient series. PATIENTS AND INTERVENTIONS: Forty consecutive patients with early CRC underwent lymphatic mapping after subserosal injection of 1 mL of isosulfan blue dye. All lymph nodes were examined by hematoxylin-eosin (HE) staining, and multiple sections of each sentinel node were examined by HE and cytokeratin immunohistochemistry (CK-IHC) staining. Primary tumors were analyzed for p53 expression using IHC staining and for beta-human chorionic gonadotropin (beta-hCG), hepatocyte growth factor receptor (c-Met), and universal melanoma antigen (uMAGE) messenger RNA expression using reverse-transcriptase polymerase chain reaction and electrochemiluminescence. RESULTS: Nine patients (23%) had positive nodes by routine HE staining. Of the remaining 31 patients with negative nodes on HE staining, 8 tumors (26%) were upstaged by CK-IHC identification of occult micrometastases. There was a direct correlation between the number of markers and the T stage (P =.001). The expression of p53, beta-hCG, c-Met, and uMAGE in primary tumors was significantly higher in the presence of nodal micrometastases vs no metastases (P =.03). CONCLUSIONS: Sentinel lymphatic mapping is an accurate method of detecting micrometastases in CRC. Molecular profiling of primary CRC tumors, similar to that used for breast cancer, may be important in predicting metastatic potential and determining which patients may benefit from adjuvant therapy.

Adult↗

PubMedDate not supplied

Combination probe and dye-directed lymphatic mapping detects micrometastases in early colorectal cancer.

Nodal metastasis is the single most important prognostic factor in early colorectal cancer (CRC). Lymphatic mapping can identify sentinel nodes for focused histopathologic examination and thereby improve the nodal staging of CRC; however, the optimal technique for identifying sentinel nodes in CRC is unclear. We hypothesized that a combination of radiotracer and blue dye would more accurately identify tumor-positive sentinel nodes than blue dye alone. Lymphatic mapping was performed in 48 consecutive patients undergoing resection for CRC and in two original patients who underwent sentinel node mapping in 1996. Prior to resection, 1% vital blue dye and radiotracer were injected around the tumor in the subserosal layer. Nodes were designated as sentinel by blue coloration and/or radioactivity. Lymphatic mapping identified at least one sentinel node in 49 patients. Focused examination of multiple sentinel node sections by means of hematoxylin and eosin and immunohistochemical analysis showed that sentinel nodes accurately predicted the status of the nodal basin in 93.8% (46 of 49) of patients. Of the 19 patients with nodal metastases, 11 had macrometastases (>.2 mm), three had micrometastases (between 2 mm and 0.2 mm), and five had isolated tumor cells or clusters (<.2 mm) identified by immunohistochemical analysis only. Patients had significantly fewer blue/radioactive ("hot") nodes than blue-only nodes (1.38 vs. 2.48 per patient; P = 0.0001). It is important to note that nodal metastases were more common in blue/hot nodes than in blue-only nodes (27.3% [19 of 68] vs. 8.8% [11 of 124]; P = 0.005). Dual-agent lymphatic mapping more accurately identifies sentinel node metastases than blue dye alone. In addition, this technique allows a more focused histopathologic examination of these nodes, in conjunction with the revised American Joint Committee on Cancer guidelines, and thereby offers the potential for significant upstaging of CRC.

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