The clinical significance of metastases in small lymph nodes is not known. Our objective was to evaluate possible relationships between the number and size of lymph node metastases and survival after potentially curative colorectal resection.
A retrospective chart review was performed in patients with Dukes'C (any T, N(1-3') M0) colorectal cancers from July 31, 1971 to December 31, 1987. All specimens underwent the lymph node clearing technique. Statistical analysis was performed with the log rank test and the Cox proportional hazards model.
In 77 patients there were 253 (8%) of 3,087 cleared lymph nodes with metastases. One hundred seventy-five (69%) of these metastatic nodes were 5 mm or less in diameter. The distal margin of resection (p = 0.011) and number of positive lymph nodes (p = 0.036) were statistically significant factors influencing overall survival. There was no significant difference in overall survival (p = 0.73) or disease-free survival (p = 0.56) whether the involved lymph nodes were < or > 5 mm in size.
Most metastatic lymph nodes were < 5 mm in diameter. Based on our results, the size of lymph node metastases do not affect disease-free or overall survival in colorectal carcinoma.
"(Bilchik AJ et al., 2003; Sobin LH, 2002) For the assessment of the lymph status it is obligatory to investigate morphologically at least 12 lymph nodes. (Martinez SR& Bilchik AJ, 2005; Rodriguez-Bigas MA et al., 1996). If lymph metastases are not detected, it is advisable to search for micrometastases (MM) A great number of authors in the literature suggest that the presence of MM is a poor prognostic factor and therefore are indicative for adjuvant therapy which would improve the prognosis in these " troublesome " 30% of the patients " without metastases " . "
"In Stage II colon cancer, the age of the patient, tumor size, specimen length, use of a structured pathology template, and academic status of the hospital are predictors of LN collection . Up to 70% of metastases are found in LNs that are < 5 mm in diameter and hence likely to be missed on routine visualization or palpation . Another challenge for pathologists relates to micro-metastases or isolated tumor cells that are missed in routine histological examinations. "
[Show abstract][Hide abstract] ABSTRACT: Although evaluation of at least 12 lymph nodes (LNs) is recommended as the minimum number of nodes required for accurate staging of colon cancer patients, there is disagreement on what constitutes an adequate identification of such LNs.
To evaluate the minimum number of LNs for adequate staging of Stage II and III colon cancer, 490 patients were categorized into groups based on 1-6, 7-11, 12-19, and ≥ 20 LNs collected.
For patients with Stage II or III disease, examination of 12 LNs was not significantly associated with recurrence or mortality. For Stage II (HR = 0.33; 95% CI, 0.12-0.91), but not for Stage III patients (HR = 1.59; 95% CI, 0.54-4.64), examination of ≥20 LNs was associated with a reduced risk of recurrence within 2 years. However, examination of ≥20 LNs had a 55% (Stage II, HR = 0.45; 95% CI, 0.23-0.87) and a 31% (Stage III, HR = 0.69; 95% CI, 0.38-1.26) decreased risk of mortality, respectively. For each six additional LNs examined from Stage III patients, there was a 19% increased probability of finding a positive LN (parameter estimate = 0.18510, p < 0.0001). For Stage II and III colon cancers, there was improved survival and a decreased risk of recurrence with an increased number of LNs examined, regardless of the cutoff-points. Examination of ≥7 or ≥12 LNs had similar outcomes, but there were significant outcome benefits at the ≥20 cutoff-point only for Stage II patients. For Stage III patients, examination of 6 additional LNs detected one additional positive LN.
Thus, the 12 LN cut-off point cannot be supported as requisite in determining adequate staging of colon cancer based on current data. However, a minimum of 6 LNs should be examined for adequate staging of Stage II and III colon cancer patients.
"This scenario suggests that Haematoxylin and Eosin staining (H&E) as the current method applied to assess the nodal status of CRC patients may not be fully adequate. Small metastases (<5 mm) are quite frequent in CRC patients . It has been proposed that understaging in CRC is linked to the presence of occult tumour cells. "
[Show abstract][Hide abstract] ABSTRACT: Accurate histopathological evaluation of resected lymph nodes (LN) is essential for the reliable staging of colorectal carcinomas (CRC). With conventional sectioning and staining techniques usually only parts of the LN are examined which might lead to incorrect tumor staging. A molecular method called OSNA (One Step Nucleic Acid Amplification) may be suitable to determine the metastatic status of the complete LN and therefore improve staging.
OSNA is based on a short homogenisation step and subsequent automated amplification of cytokeratin 19 (CK19) mRNA directly from the sample lysate, with result available in 30-40 minutes. In this study 184 frozen LN from 184 patients with CRC were investigated by both OSNA and histology (Haematoxylin & Eosin staining and CK19 immunohistochemistry), with half of the LN used for each method. Samples with discordant results were further analysed by RT-PCR for CK19 and carcinoembryonic antigen (CEA).
The concordance rate between histology and OSNA was 95.7%. Three LN were histology+/OSNA- and 5 LN histology-/OSNA+. RT-PCR supported the OSNA result in 3 discordant cases, suggesting that metastases were exclusively located in either the tissue analysed by OSNA or the tissue used for histology. If these samples were excluded the concordance was 97.2%, the sensitivity 94.9%, and the specificity 97.9%. Three patients (3%) staged as UICC I or II by routine histopathology were upstaged as LN positive by OSNA. One of these patients developed distant metastases (DMS) during follow up.
OSNA is a new and reliable method for molecular staging of lymphatic metastases in CRC and enables the examination of whole LN. It can be applied as a rapid diagnostic tool to estimate tumour involvement in LN during the staging of CRC.
Journal of Translational Medicine 09/2010; 8(1):83. DOI:10.1186/1479-5876-8-83 · 3.93 Impact Factor
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