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Background The prognostic benefits of primary tumour and lymph node (LN) downstaging after neoadjuvant chemotherapy for oesophageal adenocarcinoma are well described. Pathological primary tumour regression grading (TRG) is widely used in the assessment of response to chemotherapy and has been shown to have prognostic value in this patient group. However, there is a lack of robust evidence regarding the prognostic effect of pathological response in LN despite emerging evidence of a discrepancy, up to 25% of patients in some studies, between TRG in the primary tumour and response in regional LNs. Although primary tumour regression is routinely documented as part of the standard pathological reporting of oesophagectomy specimens, LN regression is generally overlooked despite it's potential prognostic value. The aim of this study was to investigate the relationship between pathological response in LN, tumour recurrence and survival. Methods Multicentre cohort study including 763 patients with oesophageal adenocarcinoma treated with neoadjuvant chemotherapy followed by surgery at Guy's and St Thomas’ NHS Foundation Trust (NHS-FT), The Royal Marsden NHS-FT, University Hospitals Birmingham NHS-FT, University Hospital Southampton NHS-FT and Belfast Health and Social Care Trust. Tumour regression was assessed in the primary tumour (as described by Mandard) and, retrospectively, in LNs retrieved from oesophagectomy specimens. LN were graded according to the proportion of fibrosis and residual tumour providing a LN regression score (LNRS). LNRS 1, complete response; LNRS 2, < 10% remaining tumour; LNRS 3, 10–50% remaining tumour; LNRS 4, > 50% viable tumour; LNRS 5, no evidence of response. Regression was defined as a LNRS of 1–3. Patients were classified as LN negative (no evidence of tumour or regression in any LN), complete LN-responders (evidence of regression ≥1 LN, no residual tumour in any LN), partial LN-responders (evidence of regression ≥1 LN with residual tumour ≥1 LN) and LN non-responders (no or minimal regression in any LN). Survival analysis was performed using multivariable Cox regression providing hazard ratios (HR) with 95% confidence intervals (CI) adjusting for age, gender, chemotherapy regimen, clinical stage, tumour grade, lympho-vascular invasion and primary tumour response. Results Mean age was 63 years with the majority male (86.2%). In total, 17,930 LN from 763 patients were analysed for evidence of response to chemotherapy. Overall, 243 (31.8%) patients were classified as LN negative, 62 (8.1%) as complete LN-responders, 155 (20.3%) as partial LN-responders and 303 (39.7%) as LN non-responders. Less than half (322/763, 42.2%) of patients demonstrated a pathological response in the primary tumour (Mandard score 1–3). Some patients had a LN response in the absence of a response in the primary tumour (97/431, 22.5%). Multivariable Cox regression survival analysis demonstrated improved overall survival in complete LN-responders (HR 0.37 95% CI 0.24–0.58), partial LN-responders (HR 0.70 95% CI 0.55–0.89) and LN negative patients (HR 0.34 95% CI 0.26–0.44) compared to LN non-responders. Similar results were observed for disease-free survival (complete LN-responders, HR 0.34 95% CI 0.22–0.53; partial LN-responders, HR 0.74 95% CI 0.58–0.93; LN negative, HR 0.33 95% CI 0.25–0.42). Rates of tumour recurrence were lower in patients who demonstrated a LN response or had negative LN (LN negative 23.0% vs complete LN-responders 19.4% vs partial LN-responders 50.3% vs LN non-responders 66.7%, p Conclusions In this cohort of patients with oeosphageal adenocarcinoma treated with neoadjuvant chemotherapy prior to surgical resection, LN regression was a strong predictive factor for better survival. This relationship was independent of primary tumour response, which was discordant in a significant number of patients. Complete LN-responders had equivalent survival to those with negative LN. Complete and partial LN-responders had better survival than LN non-responders. Evaluation and documentation of LN regression should be considered during the standard pathological reporting of oesophagectomy specimens.

The prognostic benefit of primary tumour and lymph node (LN) downstaging after neoadjuvant chemotherapy for oesophageal adenocarcinoma (OAC) is well described. However, there is no robust evidence regarding the prognostic effect of pathological LN regression despite emerging evidence of a discrepancy, in some patients, between tumour regression grade in the primary tumour and response in regional LNs. The aim of this study was to investigate the relationship between pathological LN regression, tumour recurrence and survival. Retrospective, multicentre cohort study including 763 patients with OAC treated with neoadjuvant chemotherapy followed by surgery at 5 high-volume tertiary referral centres in the United Kingdom. Tumour regression was assessed in the primary tumour (Mandard) and LNs retrieved from oesophagectomy specimens. Patients were classified as LN negative (no evidence of tumour or regression in any LN), complete LN-responders (evidence of regression ≥1 LN, no residual tumour in any LN), partial LN-responders (evidence of regression ≥1 LN with residual tumour ≥1 LN) and LN non-responders (no or minimal regression in any LN). Survival analysis was performed using Kaplan-Meier and Cox regression. Overall, 243 (31.8%) patients were classified as LN negative, 62 (8.1%) as complete LN-responders, 155 (20.3%) as partial LN-responders and 303 (39.7%) as LN non-responders. Some patients had a LN response in the absence of a response in the primary tumour (97/431, 22.5%). Multivariable Cox regression survival analysis (adjusting for age, gender, chemotherapy regimen, clinical stage, tumour grade, lympho-vascular invasion and primary tumour response) demonstrated improved overall survival in complete LN-responders (Hazard ratio (HR) 0.37 95% confidence interval (CI) 0.24-0.58), partial LN-responders (HR 0.70 95% CI 0.55-0.89) and LN negative patients (HR 0.34 95% CI 0.26-0.44) compared to LN non-responders. In this cohort of patients with OAC treated with neoadjuvant chemotherapy prior to surgical resection, LN regression was a strong prognostic factor independent of primary tumour response, which was discordant in a significant number of patients. Complete LN-responders had equivalent survival to those with negative LN. Complete and partial LN-responders had better survival than LN non-responders. Evaluation and documentation of LN regression should be considered during the standard pathological reporting of oesophagectomy specimens.

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 (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.

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.

AimsThe 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.MethodsIn 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.ResultsMedian 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.ConclusionsThe 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.

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 β-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.