Meeting the biologic challenge of colorectal metastases

Abstract

An overview of colorectal cancer discussed (Philip Paty) the good outcome after primary management with local control in 90-95 % of colon and 85 % in rectal cancer patients with major progression to metastases and to death related to hematogenous dissemination. The major disease pathways include the APC, aneuploid pathway involving mutations of P53, KRAS, SMAD 4, or the CMP/MSI pathway, mismatched repair defect as characterized by Lynch syndrome, the major hereditary form which may also have KRAS and P53 mutations. The common sporadic colorectal cancers are MS1 high, with many patients having BRAF and KRAS mutations. The sentinel node biopsy in colorectal cancer surgery may provide more definitive staging and perhaps modification of the extent of resection with better outcome as suggested by Dr. Saha. The identification of sentinel lymph nodes outside of the planned bowel resection may increase the resection biologically indicated by the sentinel lymph node location leading to better outcome. In a small study by Dr. Saha, the operation was enhanced in 21 % by extending the length of bowel resection, which increased node recovery to 18.5 nodes versus 12 nodes with the more conventional resection, increasing nodal recovery, and positivity to 60 % with reduction to five year recurrence rate to 9 % versus 27 % with the conventional resection. A new (Swiss) technique for pathologic node examination, the OSNA (the One Step Nucleic Acid diagnostic system), was presented which demonstrated increased detection of micro-metastases in a focused pathology study of 22 patients (Zuber) to 11 out of 15 patients versus the 7 micro-metastases identified by the standard single slide per node, and compared to 14 out of 15 with an intensive multi-slide technique. This suggests value in pursuing OSNA study by other centers with relevant clinical trials to establish its true value. An analysis of liver resection for metastatic colorectal cancer (CRC) emphasized the value of 10-year follow-up (DeAngelica). The 10-year survival of 102 patients among 612 patients was 17 % (Memorial Sloan Kettering data). At the five-year point 99 of 102 survivors were NED and 86 have been free of disease since the resection. The usual five-year figure after hepatic resection reveals that one-third of five-year survivors die from recurrence of distant disease suggesting the value of longer term follow-up in these patients. An additional question reviewed related to the role of neoadjuvant systemic chemotherapy (with response rates in the 50 % range) to produce down staging of the hepatic metastases and allow one to retrieve these patients with possible residual disease. In a series of 116 patients who had hepatic resection of CRC metastases in presence of regional node metastases, post neoadjuvant chemotherapy (normally not candidates for resection) these patients were demonstrated to have a 95 % recurrence at median time of 9 months. This raises a cautionary note to the literature report of five-year survivals in the 20-30 % range for hepatic metastases ...

Impact of Contrast-Enhanced Intraoperative Ultrasound on Operation Strategy in Case of Colorectal Liver Metastasis

“…However, that also means new challenges for the imaging of CRLM treated with chemotherapy, especially if a more targeted treatment such as anti-angiogenic agents are used [46,82]. Recent studies have shown that alternative treatment response criteria like immune-related response criteria or PERCIST may be more predictive of pathologic response in metastatic colorectal cancer than conventional criteria such as RECIST 1.1 [81,[120][121][122].…”

“…Extending the observation time of CRLM may provide valuable information about tumor biology in case of response evaluation after neoadjuvant chemotherapy in indeterminate liver lesions or disappearing CRLM [82]. Promising results for early response evaluation have been reported for PET/CT and MRI/DWI, however none of these techniques have been applied in clinical routine and further research is needed to assess their clinical value [126][127][128].…”

Simvastatin downregulated C35 expression and inhibited the proliferation of colon cancer cells Lovo and HT29 <i>in vitro </i>

“…Colon cancer is one of the leading cancer deaths worldwide (1). Chemotherapy drugs including cytotoxic agents such as irinotecan and capecitabine and targeted drugs such as cetuximab and panitumumab are usually recommended for advanced colon cancer, however, most of the patients die from metastatic diseases eventually (1).…”

“…Chemotherapy drugs including cytotoxic agents such as irinotecan and capecitabine and targeted drugs such as cetuximab and panitumumab are usually recommended for advanced colon cancer, however, most of the patients die from metastatic diseases eventually (1). Clarification of mechanisms underlying the initiation and progression of colon cancer and thus development of novel targeted drugs may lead to better treatment of this disease.…”

Tumour Microenvironment: Overview with an Emphasis on the Colorectal Liver Metastasis Pathway

“…Local invasion and cell migration ensues, along with angiogenesis, preceding viable vascular dissemination with immune evasion, extravasation with distant transportation and survival of cancer cells at another organ, resulting in metastases. Wanebo et al have recently presented a very detailed description of these phenomena [12].…”