Pathologic Lymph Node Regression After Neoadjuvant Chemotherapy Predicts Recurrence and Survival in Esophageal Adenocarcinoma: A Multicenter Study in the United Kingdom.

PURPOSE: There is limited evidence regarding the prognostic effects of pathologic lymph node (LN) regression after neoadjuvant chemotherapy for esophageal adenocarcinoma, and a definition of LN response is lacking. This study aimed to evaluate how LN regression influences survival after surgery for esophageal adenocarcinoma. METHODS: Multicenter cohort study of patients with esophageal adenocarcinoma treated with neoadjuvant chemotherapy followed by surgical resection at five high-volume centers in the United Kingdom. LNs retrieved at esophagectomy were examined for chemotherapy response and given a LN regression score (LNRS)-LNRS 1, complete response; 2, <10% residual tumor; 3, 10%-50% residual tumor; 4, >50% residual tumor; and 5, no response. Survival analysis was performed using Cox regression adjusting for confounders including primary tumor regression. The discriminatory ability of different LN response classifications to predict survival was evaluated using Akaike information criterion and Harrell C-index. RESULTS: In total, 17,930 LNs from 763 patients were examined. LN response classified as complete LN response (LNRS 1 ≥1 LN, no residual tumor in any LN; n = 62, 8.1%), partial LN response (LNRS 1-3 ≥1 LN, residual tumor ≥1 LN; n = 155, 20.3%), poor/no LN response (LNRS 4-5; n = 303, 39.7%), or LN negative (no tumor/regression; n = 243, 31.8%) demonstrated superior discriminatory ability. Mortality was reduced in patients with complete LN response (hazard ratio [HR], 0.35; 95% CI, 0.22 to 0.56), partial LN response (HR, 0.72; 95% CI, 0.57 to 0.93) or negative LNs (HR, 0.32; 95% CI, 0.25 to 0.42) compared with those with poor/no LN response. Primary tumor regression and LN regression were discordant in 165 patients (21.9%). CONCLUSION: Pathologic LN regression after neoadjuvant chemotherapy was a strong prognostic factor and provides important information beyond pathologic TNM staging and primary tumor regression grading. LN regression should be included as standard in the pathologic reporting of esophagectomy specimens.

Counting Intraepithelial Lymphocytes: A Comparison Between Routine Staining and CD3 Immunohistochemistry.

Counting intraepithelial lymphocytes (IELs) is a key part of the assessment of duodenal biopsies. Immunohistochemistry (IHC) for CD3 can aid identification of lymphocytes in this context, but it is not evident that counts on hematoxylin and eosin (H&E) and CD3 are comparable. This study aimed to compare the IEL counts in duodenal biopsies using H&E stains and CD3 IHC, and to examine the interobserver variability. Thirty-five paired H&E and CD3 sections were reviewed by 6 pathologists who counted the number of IELs per 100 enterocytes. The counts were categorized into groups: normal (<25 lymphocytes), mildly raised (25-40 lymphocytes), and markedly raised (>40 lymphocytes). CD3 IHC was associated with significantly higher IEL counts than H&E. Four cases with normal H&E counts had raised counts with CD3. There was moderate agreement between observers for both H&E and CD3. Lack of concordance between CD3 and H&E IEL counts suggests that counts derived from the 2 methods may not be comparable to each other and should not be considered equivalent. There was no significant improvement in interobserver variability with CD3 IHC.

A comparison of formalin and GEWF in fixation of colorectal carcinoma specimens: rates of lymph node retrieval and effect on TNM staging.

AIMS: The Royal College of Pathologists recommend that a median of at least 12 lymph nodes should be harvested during pathological staging of colorectal cancer. It is not always easy to harvest the required number, especially in patients with rectal cancer receiving neoadjuvant therapy. Lymph node revealing solutions, for example, GEWF, may improve nodal yield. GEWF is safe, cheap and easy to use. METHODS: In a controlled trial, lymph node yields were compared after secondary specimen dissection following either 24 h of further fixation in formalin (n=101) or GEWF immersion (n=99). The number, size and tumour status of additional lymph nodes identified were compared between groups. Twenty-seven cases that received long-course neoadjuvant therapy were also assessed. RESULTS: Median lymph node yield at primary dissection met national standards overall (19) but also in the long-course neoadjuvant therapy group (13). Lymph nodes were smaller in neoadjuvant cases compared with non-neoadjuvant cases (mean size range 1.3-5.6 mm vs 1.5-8.9 mm). The use of further fixation and GEWF detected more nodes at secondary dissection. The mean number of additional nodes harvested was greater with formalin (8.3) than GEWF (7.3). There was no significant difference in the mean size of the additional lymph nodes detected between groups (point estimate 1.02; 95% CI -0.58 to 2.63; p=0.211). Upstaging triggering adjunct chemotherapy occurred in 1% (2/200) of cases. CONCLUSIONS: The routine use of adjunct techniques to identify additional lymph nodes is unnecessary with underlying high-quality dissection practice. Emphasis should be placed upon education and training, spending appropriate time dissecting and ensuring specimens are sufficiently fixed beforehand.

Lymph node revealing solutions in colorectal cancer: should they be used routinely?

The Royal College of Pathologists (RCPath) and College of American Pathologists recommend that at least 12 lymph nodes should be harvested for adequate staging of colorectal carcinoma. Just one nodal tumour deposit upstages the malignancy from pN0 to pN1. This is critically important as node-positive patients (pN1) are considered for adjuvant chemotherapy whereas node-negative patients (pN0) may not be. It is not always easy to harvest the required number, especially in patients with rectal carcinoma who may have received neoadjuvant therapy-an increasingly common treatment. The use of neoadjuvant therapy is known to further decrease the number and size of identifiable lymph nodes within specimens, meaning that the lymph node harvest often fails to reach RCPath guidelines. Lymph node revealing solutions consisting of either single chemicals such as alcohol or acetone or compounds have been investigated to help improve the lymph node harvest in difficult specimens, for example, those received following neoadjuvant therapy. Published research evidence reviewed here suggests that lymph node revealing solutions significantly improve lymph node harvesting, and that glacial acetic acid, ethanol, water and formalin is advantageous in comparison with other revealing solutions in that it is safe, cheap, easy to use and relatively quick. However, the quantity of good evidence is limited and the clinical implications of improving lymph node harvesting require further research.

Unicryptal gallbladder adenomas in a patient with Gardner's syndrome.

Gardner's syndrome occurs when mutation of the adenomatous polyposis coli gene is associated with extra-intestinal manifestations in addition to colorectal adenomas. Only eleven cases of gallbladder adenoma in Gardner's syndrome have been previously reported in the literature. We report a case of Gardner's syndrome in which multiple adenomas are associated with unicryptal adenomas. The lesion showed cytoplasmic and nuclear expression of ß-catenin. The identification of multiple fully formed and unicryptal adenomas in the gallbladder are suggestive of Gardner's syndrome, and these patients require further investigation and follow up.