Biology-Based Surgery: The Extent of Lymphadenectomy in Cancer of the Colon

Abstract

The progression of colon cancer (CC) involves hematogenous and lymphatic spread to locoregional lymph nodes (LN), distant LN, and metastatic sites including the liver. The biological mechanisms that govern CC progression remain elusive. The Halsted model assumes an orderly, stepwise progression from the primary tumor to nearby nodes, henceforth to anatomically more distant nodes, and ultimately to distant organs. The Fisher model, on the other hand, regards the release of metastatic cells as early and essentially random events. The underlying biology has important implications for the ideal extent of surgery: when the Fisher model is correct, efforts to remove apical (central), extramesenteric, or para-aortic LN are unlikely to affect the oncological outcome. Recent data from phylogenetic studies suggest that cancer cell populations differ genetically among different LN stations and from distant metastases. Circulating tumor cells and other liquid biomarkers can be detected in the circulation of patients with early-stage disease. Local recurrence in CC is uncommon, and it is associated with a high risk of systemic progression and poor survival. Clinical studies comparing standard colectomy with extensive surgery (high ligation of the inferior mesenteric artery, complete mesocolic excision, D3 dissection, and para-aortic or extramesenteric node dissection) show that these techniques increase the LN count, while any beneficial effect on the risk of local recurrence or disease-free survival is at present uncertain due to the lack of controlled trials. Ongoing randomized trials comparing extensive vs. standard surgery for CC will generate important answers.

Complete mesocolic excision for colon cancer: current status and controversies

“…In addition to the radicality of the resection, nodal yield is influenced by tumour (tumour size, T stage, tumour infiltrating lymphocytes, differentiation, immune response, microsatellite instability high phenotype), institution (hospital size, method of specimen pathological processing) and patient factors (age, body mass index, concurrent gastrointestinal pathology). [66][67][68] Given the high risk of bias of currently available data, large randomized trials are required to assess the oncological benefit of CME with CVL/D3 dissection.…”

“…The influence of tumour biology, immune responses and neoadjuvant chemotherapy on lymph node yield and oncological outcomes 49,65 are difficult to control for in observational studies and a casual relationship has not been conclusively demonstrated. In addition to the radicality of the resection, nodal yield is influenced by tumour (tumour size, T stage, tumour infiltrating lymphocytes, differentiation, immune response, microsatellite instability high phenotype), institution (hospital size, method of specimen pathological processing) and patient factors (age, body mass index, concurrent gastrointestinal pathology) 66–68 . Given the high risk of bias of currently available data, large randomized trials are required to assess the oncological benefit of CME with CVL/D3 dissection.…”

Postoperative Quality Assessment Score Can Select Patients with High Risk for Locoregional Recurrence in Colon Cancer

“…They attribute this to occult micro-metastases or isolated tumor cells and recommend broadening the indication for post-operative chemotherapy to include these cases. To this end, CME with standardized CVL would improve accurate nodal staging by including more conventionally negative LNs that could harbor micro-metastases and isolated tumor cells, in order to categorize patients for adjuvant treatment [ 58 , 59 ].…”

Minimally Invasive Complete Mesocolic Excision with Extended Lymphadenectomy for Colon Cancer

“…In the Halsted model, progression of metastasis occurs in a stepwise fashion from the primary tumor to pericolic, intermediate, and central nodes and ultimately to distant organs. In the Fisher model, metastatic progression is non-linear and can bypass proximal nodal basins altogether [30][31][32][33]. Pattern of nodal spread has different implications on the theoretical impact of radical D3 lymphadenectomy.…”