The Simultaneous Presence of Isolated Tumour Cells and Bone Marrow Micrometastases in Stage I and II Colon Cancer—Challenging the Theory of a Chronological Pathway of Tumour Cell Dissemination

Background According to the common tenet, tumour progression is a chronological process starting with lymphatic invasion. In this respect, the meaning of bone marrow micrometastases (BMM) in patients with lymph node negative colon cancer (CC) is unclear. This study examines the relationship of isolated tumour cells (ITC) in sentinel lymph nodes (SLN) and BMM in patients in early CC. Methods BM aspirates were taken from both pelvic crests and in vivo SLN mapping was done during open oncologic colon resection in patients with stage I and II CC. Stainings were performed with the pancytokeratin markers A45-B/B3 and AE1/AE3 as well as H&E. The correlation between the occurrence of ITC+ and BMM+ and their effects on survival was examined using Cox regression analysis. Results In a total of 78 patients with stage I and II CC, 11 patients (14%) were ITC+, 29 patients (37%) BMM+. Of these patients, only two demonstrated simultaneous ITC+ /BMM+. The occurrence of BMM+ was neither associated with ITC+ in standard correlation (kappa = − 0.13 [95% confidence interval [CI] = − 0.4–0.14], p = 0.342) nor univariate (odds ratio [OR] = 0.39, 95%CI:0.07–1.50, p = 0.180) or multivariate (OR = 0.58, 95%CI: 0.09–2.95, p = 0.519) analyses. Combined detection of ITC+ /BMM+ demonstrated the poorest overall (HR = 61.60, 95%CI:17.69–214.52, p = 0.032) and recurrence free survival (HR = 61.60, 95%CI: 17.69–214.5, p = 0.032). Conclusions These results indicate that simultaneous and not interdependent presence of very early lymphatic and haematologic tumour spread may be considered as a relevant prognostic risk factor for patients with stage I and II CC, thereby suggesting the possible need to reconsider the common assumptions on tumour spread proposed by the prevalent theory of sequential tumour progression.

AGO Recommendations for the Surgical Therapy of the Axilla After Neoadjuvant Chemotherapy: 2021 Update

For many decades, the standard procedure to treat breast cancer included complete dissection of the axillary lymph nodes. The aim was to determine histological node status, which was then used as the basis for adjuvant therapy, and to ensure locoregional tumour control. In addition to the debate on how to optimise the therapeutic strategies of systemic treatment and radiotherapy, the current discussion focuses on improving surgical procedures to treat breast cancer. As neoadjuvant chemotherapy is becoming increasingly important, the surgical procedures used to treat breast cancer, whether they are breast surgery or axillary dissection, are changing. Based on the currently available data, carrying out SLNE prior to neoadjuvant chemotherapy is not recommended. In contrast, surgical axillary management after neoadjuvant chemotherapy is considered the procedure of choice for axillary staging and can range from SLNE to TAD and ALND. To reduce the rate of false negatives during surgical staging of the axilla in pN+CNB stage before NACT and ycN0 after NACT, targeted axillary dissection (TAD), the removal of > 2 SLNs (SLNE, no untargeted axillary sampling), immunohistochemistry to detect isolated tumour cells and micro-metastases, and marking positive lymph nodes before NACT should be the standard approach. This most recent update on surgical axillary management describes the significance of isolated tumour cells and micro-metastasis after neoadjuvant chemotherapy and the clinical consequences of low volume residual disease diagnosed using SLNE and TAD and provides an overview of this yearʼs AGO recommendations for surgical management of the axilla during primary surgery and in relation to neoadjuvant chemotherapy.

Evaluation of an enhanced pathological examination protocol for sentinel lymph nodes from patients with breast carcinoma

Clinical trials have shown that many patients with breast cancer with limited sentinel lymph node (SLN) metastatic disease can safely avoid axillary lymph node dissection. Ultra-staging of initially negative SLNs may not confer additional clinical benefit. Despite this, protocols of ‘enhanced pathological examination’ (EPE) are still widely used. We evaluated the impact of our EPE protocol. If initial SLN H&Es are negative, we cut three additional H&E levels at 500 µm intervals with two spare sections at each level, to allow for immunohistochemistry if necessary. Occult micrometastases or isolated tumour cells were identified, using this protocol, in 3.4%, resulting in change of N stage in 3%. 1% of patients had further axillary surgery based on these findings. Our SLN-EPE protocol provided additional information in a small number of cases and changed axillary management in a minority. It represented a significant workload for scientists and pathologists, and had time and cost implications. We concluded that emphasising careful gross examination along with judicious use of additional levels and immunohistochemistry may be more beneficial than our current protocol.