Histopathologic patterns as markers of prognosis in patients undergoing hepatectomy for colorectal cancer liver metastases – Pushing growth as an independent risk factor for decreased survival
Introduction
Yearly, 1.2 million new cases of colorectal cancer (CRC) are diagnosed worldwide and around 50% of them will develop liver metastases [1]. Hepatic resection remains the most efficient treatment for these patients; however, a strategy combining surgery with neoadjuvant chemotherapy (NAC) has gained wide acceptance. Furthermore, some of those patients have initially unresectable metastases which can be resected after down-staging with conversion chemotherapy [2], [3], [4].
Several clinical variables have been identified as valuable predictors of recurrence and survival [5], [6].
Current research is focused on finding pathological indicators which may influence treatment response. The role of surgical margin on patients' outcome after colorectal liver metastases (CRLM) resection has been thoroughly investigated [7] and is still subject of debate [8], [9], [10]. Recently, new pathologic markers of prognosis have been described. Dipen Maru et al. [11] established a pathologic predictor of survival: the tumor thickness at the tumor-normal interface (TTNI); and Rubbia-Brant et al. [12] documented a pathological tumor regression grade (TRG) system for CRLMs according to the extent of fibrosis and the amount of residual tumor cells.
In 2001, Vermeulen et al. [13] carried out one of the most interesting studies in this area and described three histological CRLM growth patterns (GP) with different angiogenic and invasive potential.
Apart from the prediction of response to chemotherapy, these pathologic patterns can also reflect important tumor-host interactions, as spontaneous necrosis of tumor metastases has been described [14].
The primary purpose of this study was to estimate the value of pathological findings as prognostic factors, analyzing their impact on overall survival (OS), disease-free survival (DFS) and liver recurrence-free survival (LRFS). Secondarily, to evaluate the influence of NAC and clinical parameters on patient's outcome.
Section snippets
Study design
The present study reviews clinical and pathological data from a total of 142 patients who underwent hepatic resection for CRLM from January 2010 to July 2013 at our surgical department.
Demographic and clinical information were collected from patients' medical records. Six of these patients had insufficient clinical data and were excluded. Another six patients were not included due to inadequate histological material. Patients undergoing rehepatectomies (20 patients) were also excluded. The
Overall, disease-free and liver recurrence-free survival
After a median follow-up period of 31.7 months (range 0–72 months), 74 patients (67%) developed recurrent disease while the remaining 36 patients (33%) were recurrence-free.
The median survival following CRLM resection was 52 months, the 3 and 5-year overall survival was 68.5% and 47.5%, respectively, while 3 and 5-year disease-free survival was 29.9 and 21.7, respectively. Forty patients (36%) died of disease, 29 of them (73%) due to progression of liver metastases and 9 patients (23%) due to
Discussion
Metastatic spread to the liver of colorectal cancer is still a challenging disease. Significant host and tumor factors are at play and need to be considered for individualized multidisciplinary management. The design of this study aimed to identify pathological prognostic factors for these patients and to discuss its value on treatment decisions.
Recent studies proved the importance of chemotherapy as neoadjuvant approach [19], [20]. In our study NAC was provided to patients with more advanced
Conflicts of interest statement
The authors declare that they do not have any conflict of interests.
Acknowledgment
The authors wish to acknowledge the leadership, mentorship, personal warmth and dedication to the Science and Art of Surgery of Professor Francisco Castro e Sousa, who sadly passed away during the review process of this article.
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2022, Surgery (United States)Citation Excerpt :This pattern paralleled with the replacement and pushing GPs as defined by Vermeulen.4 The pushing GP has also been recently described as an adverse prognostic factor for both OS and RFS.8 Regarding the GP assessment, our method relied on the analysis of the total perimeter of all metastases, which allowed us to virtually consider the whole bulk of liver metastatic disease, apart from the very few metastases treated by radiofrequency.
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2021, Seminars in Cancer BiologyCitation Excerpt :An example of the radiologic approach to this issue can be seen on Fig. 6. One interesting finding in the studies of the HGP of CRCLM is that patients with multiple metastases, the majority of the liver nodules exhibited the same HGP [28]. This finding reinforces that the HGP is a phenotypic result of the tumour-host interaction.
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Contributed equally as authors.