The novel combination of fat clearance and immunohistochemistry improves prediction of the outcome of patients with colorectal carcinomas: a preliminary study

Haboubi, Najib; Abdalla, Sayed Abdalla; Amini, S.; Clark, P.; Dougal, Mark; Dube, A; Schofield, Philip F.

doi:10.1007/s003840050143

Cited by 69 publications

(68 citation statements)

References 14 publications

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“…This seems to be even more remarkable when taking into account that the average number of collected nodes in the unstained group is 1474, which is clearly above mean values reported in the literature for conventional techniques. 6,12,22 Fat clearance methods, or complete fat embedding, produced lymph node numbers between 55 and 87 10,17,23 and showed increased identification of positive nodes. However, these techniques are time consuming and laboring.…”

Section: Discussionmentioning

confidence: 99%

Methylene blue injection into the rectal artery as a simple method to improve lymph node harvest in rectal cancer

et al. 2007

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Adequate lymph node assessment in colorectal cancer is crucial for prognosis estimation and further therapy stratification. However, there is still an ongoing debate on required minimum lymph node numbers and the necessity of advanced techniques such as immunohistochemistry or PCR. It has been proven in several studies that lymph node harvest is often inadequate under routine analysis. Lymph nodes smaller than 5 mm are especially concerning as they can carry the majority of metastases. These small, but affected lymph nodes may escape detection in routine analysis. Therefore, fat-clearing protocols and sentinel techniques have been developed to improve accuracy of lymph node staging. We describe a novel and simple method of ex vivo methylene blue injection into the superior rectal artery of rectal cancer specimens, which highlights lymph nodes and makes them easy to detect during manual dissection. Initially, this method was developed for proving accuracy of total mesorectal excision. We performed a retrospective study comparing lymph node recovery of 12 methylene blue stained and an equal number of unstained cases. Lymph node recovery differed significantly with average lymph node numbers of 2777 and 1474 (Po0.001) for the methylene blue and the unstained group, respectively. The largest difference was found in size groups between 1 and 4 mm causing a shift in size distribution toward smaller nodes. Metastases were confirmed in 21 and 19 lymph nodes occurring in five and four cases, respectively. Hence, we conclude that methylene blue injection technique improves accuracy of lymph node staging by heightening the lymph node harvest in rectal resections. In our experience, it is a very simple time and cost effective method that can be easily established under routine circumstances.

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Section: Discussionmentioning

confidence: 99%

Methylene blue injection into the rectal artery as a simple method to improve lymph node harvest in rectal cancer

et al. 2007

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“…Relevant articles were identified through a PUBMED search using the terms "colorectal cancer," "lymph nodes," and "micrometastasis," Additional articles were identified through careful review of the referenced articles from these initially identified publications. [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] Thus, the reviewed studies consistently evaluate the pN0 LN from stage 1 and stage 2 CRC patients (in some studies referred to as Dukes A and B) for the presence of occult metastases. The following aspects were considered with regard to each study: i) size of study including number of stage 1 and 2 patients and percentage of rectal cancer patients; ii) method used for occult metastasis detection; iii) potential for sampling error (includes sectioning analysis, number of slides, sections, and levels of sections per LN, and number of LNs reviewed per patient); iv) quality control of original pathological diag- nosis; v) percentage of patients that were upstaged; vi) mean or median follow-up (5-year survival and recurrence data are ideal); and vii) antibodies and/or markers used for IHC or PCR.…”

Section: Search Methods and Article Selectionmentioning

confidence: 99%

“…9 In another study, the technique of xylene fat clearance was used to increase the amount of nodes sampled per patient to 51. 11 Only 5 of 11 IHC studies examined the recommended 12 or more nodes per patient necessary for accurate staging. The number of LNs examined by molecular methods ranged between 2 and 15.…”

Section: Attention To Samplingmentioning

confidence: 99%

Is Occult Lymph Node Disease in Colorectal Cancer Patients Clinically Significant?

Nicastri

Doucette

Godfrey

et al. 2007

The Journal of Molecular Diagnostics

171

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The clinical significance of micrometastasis of colorectal cancer (CRC) to regional lymph nodes remains controversial. In this review, we analyze publications that have evaluated the clinical significance of occult lymph node metastasis in CRC. An extensive literature search identified 19 publications that evaluated the clinical significance of micrometastatic CRC by various methods, including immunohistochemistry (IHC; n ‫؍‬ 13) and reverse transcription-polymerase chain reaction (RT-PCR, n ‫؍‬ 6). These studies were reviewed for methodology and findings. Significant limitations in methodology were identified, including inconsistent histological definitions of micrometastatic disease, poor sampling because of an inadequate number of lymph nodes or number of sections per lymph node analyzed, lack of conformity with respect to IHC antibody or RT-PCR marker, and inadequate power because of small sample size. Micrometastatic lymph node metastasis identified by RT-PCR was consistently found to be prognostically significant, but this was not true of micrometastatic disease identified by IHC. RT-PCR analysis of lymph nodes with specific markers can help identify pN0 (pathological-negative lymph node) CRC patients at increased risk for recurrence. The identification of occult disease by IHC techniques may also ultimately prove to be associated with worse outcome, but a number of inadequately powered studies have concluded conversely.

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“…2,6,7 This variation may be due to the size of the specimen, the number of regional lymph nodes present in the specimen, and the number of nodes with metastases present. 3,8 Pathologists also vary in their diligence, skill, and patience in dissecting the lymph nodes of a surgical specimen. 9 In this study, we enrolled 15 randomly chosen colon resections, which were predominantly a tumor stage of T3.…”

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confidence: 99%

Efficacy of manual dissection of lymph nodes in colon cancer resections

et al. 2004

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The adequacy of lymph node dissection of colonic resection specimens influences the clinical and pathologic staging, leading to important postsurgical treatment decisions. Although manual lymph node dissection is the current standard at most institutions, recent statistical studies indicate that all lymph nodes, including those measuring 1-2 mm, should be recovered to be assured of lymph node negative status. Thus, we tested the efficacy of gross dissection by submitting the entire residual mesenteric fat. We analyzed 15 randomly chosen colonic resections (2 pT1, 1 pT2, 11 pT3, 1 pT4). After standard gross dissection of lymph nodes and submission of colonic material for diagnosis, the entire remaining mesenteric material was dehydrated over several days by serial washing in alcohol and acetone. All of the mesenteric tissue was submitted for histology. The average number of nodes found by original gross inspection was 20.8, while the average number of additional nodes found after clearing was 68.6. In all, 83% of the additional nodes were 2.0 mm or less in size. There were seven pN0 cases; one was upstaged by additional findings that may have been artifactual. There were four pN1 cases; three were upstaged to pN2 after submission of the mesenteric material. All four pN2 tumors had additional metastases identified. In all, 75% of all positive nodes were under 2.0 mm in size. In this limited sample, standard gross dissection proved sufficient for most pN0 tumors to remain node negative. However, our findings within the pN1 group show that examination of all of the mesenteric material may be necessary to be assured of correct pN status. Keywords: colon; adenocarcinoma; lymph node; clearing; dissection; staging; prognosisThe presence or absence of lymph node metastasis is pivotal for predicting the clinical outcome of patients who have undergone radical surgery for colorectal carcinoma.1 Lymph nodes are an integral component of the TNM classification system, a major determinant of adjunct therapy, and a prognostic marker in colorectal adenocarcinoma.2 Recovering a greater number of lymph nodes guards against missing a lymph node metastasis and allows for more accurate staging of patients. The identification of a single lymph node metastasis is sufficient to offer adjunctive therapy. The most important determinant of survival is the presence or absence of metastases in regional lymph nodes.3 Thus, the detection and examination of the largest possible number of lymph nodes are essential for correct staging, therapeutic decisions, and prognosis. 4,5 Despite claims of a meticulous search for lymph nodes in surgical specimens, wide variations in the number of total nodes and lymph node metastases continue to exist. 2,6,7 This variation may be due to the size of the specimen, the number of regional lymph nodes present in the specimen, and the number of nodes with metastases present.3,8 Pathologists also vary in their diligence, skill, and patience in dissecting the lymph nodes of a surgical specimen. 9In this study, we enr...

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The novel combination of fat clearance and immunohistochemistry improves prediction of the outcome of patients with colorectal carcinomas: a preliminary study

Cited by 69 publications

References 14 publications

Methylene blue injection into the rectal artery as a simple method to improve lymph node harvest in rectal cancer

Methylene blue injection into the rectal artery as a simple method to improve lymph node harvest in rectal cancer

Is Occult Lymph Node Disease in Colorectal Cancer Patients Clinically Significant?

Efficacy of manual dissection of lymph nodes in colon cancer resections

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