Project description:BackgroundLymph node status and lymph node count (LNC) are predictors of colorectal cancer outcome. Under-sampling of lymph nodes may lead to clinically relevant stage migration.MethodsColorectal cancer (CRC) cases with a synoptic report, accessioned 2012-2020 at a regional laboratory, were extracted and retrospectively studied. LNC, positive lymph node count (PLNC), tumour deposits present (TDpos), and 'y' (staging) prefix (YS) were retrieved and tabulated by pathologist using custom software. Statistical analyses were done with R.Data and resultsThe cohort had 2,543 CRC resections. Seventeen pathologists interpreted >50 cases (range: 56-356) each and collectively saw 2,074. After cases with unavailable data were purged, 2,028 cases remained with 43,996 lymph nodes, of which 2,637/43,996 were positive. 368 cases had a 'y' prefix, and 379 had TDpos. The 17 pathologists' median LNC/case was 19.0 (range: 14.0-24.0), and the mean PLNC per case was 1.4 (range: 1.0-2.0). Kruskal-Wallis rank sum tests showed there were differences in LNC (p<0.001) among pathologists; however, PLNC did not show this association (p = 0.2917). T-tests showed that mean LNC (p<0.001) and PLNC (p<0.035) differed between YS. 138 of 2,028 cases had less than the 12 LNC target. Logistic regression revealed a strong association between meeting the LNC target and pathologist (p<0.001) but TDpos was non-predictive (p = 0.4736).ConclusionsPositive lymph node call rate has a good consistency in the laboratory; however, lymph node count varies significantly between pathologists. Standardized counting criteria are needed to improve uniformity and could be aided by synoptic reporting data.
Project description:Lymph node stages (pN stages) are primary contributors to survival heterogeneity of the 7th AJCC staging system for colorectal cancer (CRC), indicating spaces for modifications. To implement the modifications, we selected eligible CRC patients from the Surveillance Epidemiology and End Results (SEER) database as participants in a training (n = 6675) and a test cohort (n = 6760), and verified tumor deposits to be metastatic lymph nodes to derive modified lymph node count (mLNC), lymph node ratio (mLNR), and positive lymph node count (mPLNC). After multivariate Cox regression analyses with forward stepwise elimination of the mLNC and mPLNC for the training cohort, a nomogram was constructed to predict overall survival (OS) via incorporating preoperative carcinoembryonic antigen, pT stages, negative lymph node count, mLNR and metastasis. Internal validations of the nomogram showed concordance indexes (c-index) of 0.750 (95% CI, 0.736-0.764) and 0.749 before and after corrections for overfitting. Serial performance evaluations indicated that the nomogram outperformed the AJCC stages (c-index = 0.725) with increased accuracy, net benefits, risk assessment ability, but comparable complexity and clinical validity. All the results were reproducible in the test cohort. In summary, the proposed nomogram may serve as an alternative to the AJCC stages. However, validations with longer follow-up periods are required.
Project description:Background: The retrieved lymph node (LN) count has been confirmed as a prognostic indicator in various cancers. However, the correlation between LN counts and patient prognosis in gastric cancer with node-positive is not fully studied. Methods: A total of 8475 patients undergoing gastrectomy in Surveillance, Epidemiology, and End Results Program (SEER)-registered gastric cancer were analyzed. Kaplan-Meier methods and multivariable Cox regression models were used to analyze long-term outcomes and risk factors. Moreover, nomograms including LN counts were established to predict overall survival (OS) and cancer-specific survival (CSS), and Harrell's concordance index (c-index) was adopted to evaluate prediction accuracy. Results: Patients were stratified into 1-6, 7-14, and > 14 subgroups according to the optimal cutoff for retrieved LNs in terms of 5-year CSS. Further analysis indicated that higher LN counts were an independent predictor of longer survival in each N category. Nomograms on CSS and OS were established according to all significant factors, and c-indexes were 0.663 and 0.654 (P< 0.001), respectively. Conclusions: These results indicated that the more the LNs retrieved, the better the survival would be. Nomograms incorporating LN counts can be recommended as practical models to provide more accurate prognostic information for GC patients.
Project description:BackgroundThe quality of care of patients receiving colorectal resections has conventionally relied on individual metrics. When discussing with patients what these outcomes mean, they often find them confusing or overwhelming. Textbook oncological outcome (TOO) is a composite measure that summarises all the 'desirable' or 'ideal' postoperative clinical and oncological outcomes from both a patient's and doctor's point of view. This study aims to evaluate the incidence of TOO in patients receiving robotic colorectal cancer surgery in five robotic colorectal units and understand the risk factors associated with failure to achieve a TOO in these patients.MethodsWe present a retrospective, multicentric study with data from a prospectively collected database. All consecutive patients receiving robotic colorectal cancer resections from five centres between 2013 and 2022 were included. Patient characteristics and short-term clinical and oncological data were collected. A TOO was achieved when all components were realized-no conversion to open, no complication with a Clavien-Dindo (CD) ≥ 3, length of hospital stay ≤ 14, no 30-day readmission, no 30-day mortality, and R0 resection. The main outcome measure was a composite measure of "ideal" practice called textbook oncological outcomes.ResultsA total of 501 patients submitted to robotic colorectal cancer resection were included. Of the 501 patients included, 388 (77.4%) achieved a TOO. Four patients were converted to open (0.8%); 55 (11%) had LOS > 14 days; 46 (9.2%) had a CD ≥ 3 complication; 30-day readmission rate was 6% (30); 30-day mortality was 0.2% (1); and 480 (95.8%) had an R0 resection. Abdominoperineal resection was a risk factor for not achieving a TOO.ConclusionsRobotic colorectal cancer surgery in robotic centres achieves a high TOO rate. Abdominoperineal resection is a risk factor for failure to achieve a TOO. This measure may be used in future audits and to inform patients clearly on success of treatment.
Project description:The benefits and prognosis of RPLND in CRC have not yet been fully established. This systematic review aimed to evaluate the outcomes for CRC patients with RPLNM undergoing RPLND. A literature search of MEDLINE, EMBASE, EMCare, and CINAHL identified studies from between January 1990 and June 2022 that reported data on clinical outcomes for patients who underwent RPLND for RPLNM in CRC. The following primary outcome measures were derived: postoperative morbidity, disease free-survival (DFS), overall survival (OS), and re-recurrence. Nineteen studies with a total of 541 patients were included. Three hundred and sixty-three patients (67.1%) had synchronous RPLNM and 178 patients (32.9%) had metachronous RPLNM. Perioperative chemotherapy was administered in 496 (91.7%) patients. The median DFS was 8.6-38.0 months and 5-year DFS was 24.4% (10.0-60.5%). The median OS was 25.0-83.0 months and 5-year OS was 47.0% (15.0-87.5%). RPLND is a feasible treatment option with limited morbidity and possible oncological benefit for both synchronous and metachronous RPLNM in CRC. Further prospective clinical trials are required to establish a better evidence base for RPLND in the context of RPLNM in CRC and to understand the timing of RPLND in a multimodality pathway in order to optimise treatment outcomes for this group of patients.
Project description:Adequate lymph node evaluation is recommended for optimal staging in patients with malignant neoplasms including breast cancer. However, the role of negative lymph nodes (LNs) remains unclear in breast cancer according to N substage (N1, N2, and N3). In this study, for the first time, we analyzed the prognostic significance of negative LNs in breast cancer patients. A critical relationship was observed between negative LN count and survival, independent of patient characteristics and other related molecular variables including estrogen receptor (PR) status, progesterone receptor (ER) status, human epidermal growth factor receptor 2 (HER2) status, depth of tumor invasion and degree of differentiation. This research is of great importance in providing more information about the prognosis of breast cancer by statistical analysis of negative lymph nodes and can serve as a useful supplement to the current pathological system.
Project description:BackgroundMyofibroblasts have an important role in regulating the normal colorectal stem cell niche. While the activation of myofibroblasts in primary colorectal cancers has been previously described, myofibroblast activation in lymph node metastases has not been described before.MethodsParaffin-embedded lymph node sections from patients with macrometastases, micrometastases and isolated tumour cells were stained to identify myofibroblasts and to characterise the distribution of different cell types in tumour-containing lymph nodes. The extent of myofibroblast presence was quantified and compared with the size of the metastasis and degree of proliferation and differentiation of the cancer cells.ResultsWe show substantial activation of myofibroblasts in the presence of colorectal metastases in lymph nodes, which is intimately associated with glandular structures, both in micro- and macrometastases. The degree of activation is positively associated with the size of the metastases and the proportion of Ki67+ve cancer cells, and negatively associated with the degree of enterocyte differentiation as measured by CK20 expression.ConclusionThe substantial activation of myofibroblasts in tumour-containing lymph nodes strongly suggests that these metastatic cancer cells are still significantly dependent on their microenvironment. Further understanding of these epithelial-mesenchymal interactions could lead to the development of new therapies in metastatic disease.
Project description:The number of recovered lymph nodes is associated with good prognosis among colon cancer patients undergoing surgical resection. However, little has been known on prognostic significance of lymph node count after adjusting for host immune response to tumor and tumoral molecular alterations, both of which are associated with the lymph node count and patient survival.Among 716 colorectal cancers (stages 1-4) in two independent prospective cohorts, we examined patient survival in relation to the negative lymph node count and lymph node ratio (LNR; positive to total lymph node counts). Cox proportional hazard models were used to compute hazard ratio of deaths, adjusted for patient, specimen, and tumoral characteristics, including lymphocytic reactions, KRAS and BRAF mutations, p53 expression, microsatellite instability (MSI), the CpG island methylator phenotype (CIMP), and LINE-1 methylation.Compared with patients with 0-3 negative lymph nodes, patients with 7-12 and > or =13 negative nodes experienced a significant reduction in cancer-specific and overall mortality in Kaplan-Meier analysis (log-rank P<0.0001), univariate Cox regression (P(trend)<0.0001), and multivariate analysis (P(trend)<0.0003), independent of potential confounders examined. The benefit associated with the negative node count was apparent across all stages, although the effect was significantly greater in stages 1-2 than stages 3-4 (P(interaction)=0.002). In both stage 3 and stage 4, smaller LNR was associated with improved survival (log-rank P<0.0001).The negative lymph node count is associated with improved survival of colorectal cancer patients, independent of lymphocytic reactions to tumor and tumoral molecular features including MSI, CIMP, LINE-1 hypomethylation and BRAF mutation.
Project description:BackgroundCurrently, young colon cancer (CC) patients continue to increase and represent a heterogeneous patient group. The aim of this study was to explore the optimal minimum lymph node count after CC resection for young patients.MethodsWe performed a comprehensive search of the Surveillance, Epidemiology, and End Results (SEER) database, 2360 CC patients aged from 20 to 40 were analyzed. X-tile was used to determine the optimal cut-off point of lymph node based on survival outcomes of young patients. The cancer specific survival (CSS) was estimated with Kaplan-Meier method, the Cox proportional hazards regression model was used to analyse independent prognostic factors and exact 95% confidence intervals (CIs).ResultsUsing X-tile analysis, 22-node measure was identified as the optimal choice for CC patients aged < 40. The 5-year CSS were 85.8% and 80.9% for patients examining ≥22 nodes and < 22 nodes. Furthermore, we identified that examining < 22 nodes was an independent adverse prognostic factor in patients aged < 40. In addition, the revised 22-node measure could examine more positive nodes than the standard 12-node measure in young patients.ConclusionsFor young colon cancer patients, the lymph node examination should be differently evaluated. We suggest that 22-node measure may be more suitable for CC patients aged < 40.Trial registrationRetrospectively registered.
Project description:Lymph node (LN) status after surgery for rectal cancer is affected by preoperative radiotherapy. The purpose of this study was to perform a population-based evaluation of the impact of pathologic LN status after neoadjuvant radiotherapy on survival. A total of 1,650 patients receiving neoadjuvant chemotherapy in Surveillance, Epidemiology, and End Results Program (SEER)-registered ypIII stage rectal cancer was analyzed. We identified the optimal cutoff for retrieved LNs as 10 (χ2 = 14.006, P < 0.001), which was validated as an independent prognosis factors in a Cox regression model. Further analysis showed that the LN count was only a prognosis factor with the number from 8 to 16(except for 13).After the number 16, the 5-year survival rate decreased gradually. Collectively, our results confirmed that the number of LNs in yp III stage rectal patients was a prognosis factor only with the numbers from 8 to 16(except for 13). Using the total mesorectal excision technique with an adequate pathologic examination, a large number of LNs retrieved (≥17) might indicate worse tumor response grade and poorer survival.