The Value of Sentinel Lymph Node Mapping for the Staging of Node-Negative Colon Cancer

Objectives: Mediation analysis to assess the protective impact of sentinel lymph node (SLN) mapping on prognosis and survival of patients with colon cancer through a more precise evaluation of the lymph node (LN) status. Background: Up to 20% of patients with node-negative colon cancer develop disease recurrence. Conventional histopathological LN examination may be limited in describing the real metastatic burden of LN. Methods: Data of 312 patients with stage I & II colon cancer was collected prospectively. Patients were either staged using intraoperative SLN mapping with multilevel sectioning and immunohistochemical staining of the SLN or conventional techniques. The value of the SLN mapping for the detection of truly node-negative patients was assessed using Cox regression and mediation analysis. Results: SLN mapping was performed in 143 patients. Disease recurrence was observed in 13 (9.1%) patients staged with SLN mapping and in 27 (16%) staged conventionally. Five-year overall survival (OS) rate was 82.7% (95% confidence interval [CI], 76.5–89.4%) with SLN mapping compared with 65.8% (95% CI, 58.8–73.7%). Five-year cancer-specific survival (CSS) was 95.1% (95% CI, 91.3–99.0%) with SLN mapping compared with 92.5% (95% CI, 88.0–97.2%). Node-negative staging with SLN mapping was associated with significantly better OS (hazard ratio [HR], 0.64; 95% CI, 0.56–0.72; P < 0.001) and CSS (HR, 0.49; 95% CI, 0.39–0.61; P < 0.001) in multivariate analysis. Mediation analysis confirmed a direct protective effect of SLN mapping on OS (HR, 0.78; 95% CI, 0.52–0.96; P < 0.01) and disease-free survival (DFS) (HR, 0.75; 95% CI, 0.48–0.89; P < 0.01). Conclusions: Staging performed by SLN mapping with multilevel sectioning provides more accurate results than conventional staging. The observed clinically relevant and statistically significant benefit in OS and DFS is explained by a more accurate detection of positive LN by SLN mapping

Evaluation of the prognostic relevance of the recommended minimum number of lymph nodes in colorectal cancer—a propensity score analysis

Purpose Nodal status in colorectal cancer (CRC) is an important prognostic factor, and adequate lymph node (LN) staging is crucial. Whether the number of resected and analysed LN has a direct impact on overall survival (OS), cancer-specific survival (CSS) and disease-free survival (DFS) is much discussed. Guidelines request a minimum number of 12 LN to be analysed. Whether that threshold marks a prognostic relevant cut-off remains unknown. Methods Patients operated for stage I–III CRC were identified from a prospectively maintained database. The impact of the number of analysed LN on OS, CSS and DFS was assessed using Cox regression and propensity score analysis. Results Of the 687 patients, 81.8% had ≥ 12 LN resected and analysed. Median LN yield was 17.0 (IQR 13.0–23.0). Resection and analysis of ≥ 12 LN was associated with improved OS (HR = 0.73, 95% CI: 0.56–0.95, p = 0.033), CSS (HR 0.52, 95% CI: 0.31–0.85, p = 0.030) and DFS (HR = 0.73, 95% CI: 0.57–0.95, p = 0.030) in multivariate Cox analysis. After adjusting for biasing factors with propensity score matching, resection of ≥ 12 LN was significantly associated with improved OS (HR = 0.59; 95% CI: 0.43–0.81; p = 0.002), CSS (HR = 0.34; 95% CI: 0.20–0.60; p < 0.001) and DFS (HR = 0.55; 95% CI: 0.41–0.74; p < 0.001) compared to patients with < 12 LN. Conclusion Eliminating biasing factors by a propensity score matching analysis underlines the prognostic importance of the number of analysed LN. The set threshold marks the minimum number of required LN but nevertheless represents a cut-off regarding outcome in stage I–III CRC. This analysis therefore highlights the significance and importance of adherence to surgical oncological standards

High myeloperoxidase positive cell infiltration in colorectal cancer is an independent favorable prognostic factor

BACKGROUND Colorectal cancer (CRC) infiltration by adaptive immune system cells correlates with favorable prognosis. The role of the innate immune system is still debated. Here we addressed the prognostic impact of CRC infiltration by neutrophil granulocytes (NG). METHODS A TMA including healthy mucosa and clinically annotated CRC specimens (n = 1491) was stained with MPO and CD15 specific antibodies. MPO+ and CD15+ positive immune cells were counted by three independent observers. Phenotypic profiles of CRC infiltrating MPO+ and CD15+ cells were validated by flow cytometry on cell suspensions derived from enzymatically digested surgical specimens. Survival analysis was performed by splitting randomized data in training and validation subsets. RESULTS MPO+ and CD15+ cell infiltration were significantly correlated (p<0.0001; r = 0.76). However, only high density of MPO+ cell infiltration was associated with significantly improved survival in training (P = 0.038) and validation (P = 0.002) sets. In multivariate analysis including T and N stage, vascular invasion, tumor border configuration and microsatellite instability status, MPO+ cell infiltration proved an independent prognostic marker overall (P = 0.004; HR = 0.65; CI:±0.15) and in both training (P = 0.048) and validation (P = 0.036) sets. Flow-cytometry analysis of CRC cell suspensions derived from clinical specimens showed that while MPO+ cells were largely CD15+/CD66b+, sizeable percentages of CD15+ and CD66b+ cells were MPO-. CONCLUSIONS High density MPO+ cell infiltration is a novel independent favorable prognostic factor in CRC

Factors predicting in-breast tumor recurrence after breast-conserving surgery

PURPOSE: The main objectives of this study were to identify risk factors for local in-breast tumor recurrence after breast-conservation and to evaluate the impact of IBTR (in-breast tumor recurrence) on overall survival. METHODS: A total of 335 consecutive patients with 346 invasive and in situ breast cancers were treated with breast conserving therapy. Univariate and multivariate statistical analysis were performed and survival rates were calculated and analyzed using the Kaplan-Meier method. RESULTS: With a median follow-up period of 70.6 months 14 patients (4%) developed an IBTR. Overall survival and the disease-free 8-year actuarial survival of patients were 95% and 93%, respectively. The overall survival of patients with tumour recurrence on any site was significantly shorter than of those without recurrence (64% versus 85% after 8 years of follow-up; P > 0.0001). Similarly, overall survival was significantly reduced in patients with distant metastases compared to all others without distant disease (88% versus 40% after 8 years; P > 0.0001). In contrast, overall survival of patients who experienced IBTR did not differ significantly from the group of patients who never developed IBTR (87% versus 70% after 8 years of follow-up). By univariate analysis, lobular carcinoma, high grade tumours, multifocality, concomitant LCIS and DCIS, the absence of estrogene and progesterone receptor status, as well as R1-status, were significant predictors of IBTR. By multivariate analysis, only R1-status (P > 0.002) and the presence of LCIS around the invasive tumour (P > 0.03) remained as significant factors predicting IBTR. CONCLUSIONS: Concomitant lobular carcinomas in situ, as well as R1 surgical status are independent significant risk factors for in breast tumor recurrence after breast conserving therapy

Tumornachsorge nach potentiell kurativer Resektion eines Karzinoms

Surveillance programs have been recommended for colorectal and breast cancer patients in several countries, and appropriate surveillance guidelines have been issued by various societies. The Swiss Society of Gastroenterology consensus paper recommends a surveillance program for patients after curative resection of colorectal cancer (CRC), and the respective guidelines are updated regularly. Early detection of recurrent disease from CRC allows treatment with intention to cure. Five year survival rates after treatment for recurrent CRC can reach up to 50 % or more. Therefore tumor surveillance in CRC is important, and there is compelling evidence that patients benefit from intensive surveillance. In addition to clinical controls, measurements of carcinoembryonal antigen, colonoscopies and thoraco-abdominal CT scans should be performed on a regular basis. For surveillance of breast cancer (BC) patients, a regular schedule is recommended as well. However, this surveillance program is more focussing on the detection of possible loco-regional tumor relapse, as curative therapy of BC metastases is much less frequently possible than in CRC patients. Irrespective of the underlying tumor entity, surveillance is an important and challenging process that should be coordinated by one single physician. It is crucial that all involved physicians are aware of their responsibility and that they are informed about the respective surveillance program and its benefit to the patient

Sentinel lymph node procedure leads to upstaging of patients with resectable colon cancer: results of the Swiss prospective, multicenter study sentinel lymph node procedure in colon cancer

The value of the sentinel lymph node (SLN) procedure in colon cancer patients remains a matter of debate. The objective of this prospective, multicenter trial was 3-fold: to determine the identification rate and accuracy of the SLN procedure in patients with resectable colon cancer; to evaluate the learning curve of the SLN procedure; and to assess the extent of upstaging due to the SLN procedure

Prognostic impact and therapeutic implications of sentinel lymph node micro-metastases in early-stage breast cancer patients

The prognostic value of sentinel lymph node (SLN) micro-metastases and the question whether patients with SLN micro-metastases should undergo axillary lymph node dissection remain a matter of great debate. Based on the current literature and on our own data, we provide suggestive evidence that SLN micro-metastases in early stage breast cancer patients appear to have prognostic value and should impact the decision-making regarding adjuvant therapy, however, do not necessarily require further surgical treatment