Histopathological growth patterns determines the outcomes of colorectal cancer liver metastasis that have undergone liver resection (original) (raw)
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European Journal of Surgical Oncology
Introduction: The histological growth pattern (HGP) of colorectal liver metastases (CRLMs) reflects tumor biology and local infiltrating behavior. In patients undergoing surgery for CRLMs, we investigated whether HGP and surgical margin status interact when influencing prognosis. Methods: Clinicopathological data, margin status, and HGP were reviewed in patients who underwent resection of CRLMs. R1 margin was defined when cancer cells were present at any point along the margin. HGPs were scored according to international guidelines, identifying patients with desmoplastic (DHGP) or non-desmoplastic (non-DHGP) CRLMs. Results: Among 299 patients, 16% had R1 resection and 81% had non-DHGP CRLMs. Non-DHGP was the only predictive factor for R1 resection (18.7% versus 7.4% in DHGP, p = 0.04). Poorer 5-year overall survival was observed in both R1 and non-DHGP groups in univariate analysis (27.6% in R1 versus 45.6% in R0, p = 0.026, and 37.2% in non-DHGP versus 59.2% in DHGP, p = 0.013), whereas non-DHGP but not R1 remained associated with worse prognosis in multivariate analysis. In patients with non-DHGP, R1 margin has no prognostic impact. Conclusions: In patients undergoing resection of CRLMs, the prognostic value of poor tumor biology, such as in patients with non-DHGP, exceeds that of surgical radicality.
European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology, 2018
Liver resection combined with neoadjuvant chemotherapy (NAC) has reported notable results in patients with colorectal liver metastases (CRLM). Tumoral response to NAC is associated with specific histopathologic patterns with prognostic implications. The main objective of this study was to evaluate the influence of pathological findings on overall survival (OS), disease-free survival (DFS) and liver recurrence-free survival (LRFS). Analysis of clinical and outcome data from 110 patients who underwent first CRLM resection between January 2010 and July 2013. Blinded pathological review of histological material of several parameters: resection margin, tumor regression grade (TRG), tumor thickness at the tumor-normal interface (TTNI) and the growth pattern (GP). The median survival following hepatic resection was 52 months and 3- and 5- year Kaplan-Meier estimates were 69 and 48%, respectively. Seventy-four patients developed recurrent disease. Oxaliplatin-based chemotherapy was signific...
Maximum Diameter and Number of Tumors as a New Prognostic Indicator of Colorectal Liver Metastases
In vivo (Athens, Greece)
Surgical resection is currently considered the only potentially curative option as a treatment strategy of colorectal liver metastases (CRLM). However, the criteria for selection of resectable CRLM are not clear. The aim of this study was to confirm a new prognostic indicator of CRLM after hepatic resection. One hundred thirty nine patients who underwent initial surgical resection from 1994 to 2015 were investigated retrospectively. Prognostic factors of overall survival including the product of maximum diameter and number of metastases (MDN) were analyzed. Primary tumor differentiation, vessel invasion, lymph node (LN) metastasis, non-optimally resectable metastases, H score, grade of liver metastases, resection with non-curative intent and MDN were found to be prognostic factors of overall survival (OS). In multivariate analyses of clinicopathological features associated with OS, MDN and non-curative intent were independent prognostic factors. Patients with MDN ≥30 had shown signi...
Tumor growth pattern as predictor of colorectal liver metastasis recurrence
BACKGROUND: Surgical resection is the gold standard therapy for the treatment of colorectal liver metastases (CRM). The aim of this study was to investigate the impact of tumor growth patterns on disease recurrence. METHODS: We enrolled 91 patients who underwent CRM resection. Pathological specimens were prospectively evaluated, with particular attention given to tumor growth patterns (infiltrative vs pushing).
European Journal of Surgical Oncology (EJSO), 2016
Introduction: We evaluated the impacts of a series of novel histopathological factors on clinical-surgical outcomes and survival of patients who underwent surgery for colorectal cancer liver metastasis, with and without neoadjuvant chemotherapy. Materials and methods: A prospective database including 150 consecutive patients who underwent 183 hepatic resections for metastatic colorectal cancer was evaluated. Among them, 74 (49.3%) received neoadjuvant chemotherapy before surgery. The histopathological factors studied were: a) microsatellitosis, b) type and pattern of tumour growth, c) nuclear grade and the number of mitoses/mm 2 , d) perilesional pseudocapsule, e) intratumoural fibrosis, f) lesion cellularity, g) hypoxic-angiogenic perilesional growth pattern, and h) the tumour normal interface. Results: Three or more metastatic lesions, R1 resection margins, and <50% tumour necrosis were prognostic factors for a worse OS, but only the former was confirmed to be an independent prognostic factor in the multivariate analysis. Furthermore, tumour fibrosis <40% and cellularity >10% were predictive of a worse neoadjuvant therapy response, but these findings were not confirmed in the multivariate analysis. Finally, tumour necrosis <50%, cellularity >10%, and TNI >5 mm were prognostic factors for a worse DFS and AS in the univariate but not in the multivariate analysis. Conclusions: Several factors seem to influence the outcomes of surgery for colorectal cancer liver metastasis, especially the number of the lesions, the margins of resection, the percentage of necrosis and fibrosis, as well as the cellularity and the TNI.
Surgery, Gastroenterology and Oncology, 2017
Backgound: Several clinical risk factors for patients undergoing liver resection for colorectal liver metastases were suggested. The purpose of the study was to evaluate the prognostic factors for survival after resection of liver metastases from colorectal cancer in a high volume center for both hepatobiliary and colorectal surgery. Methods: We completed a retrospective analysis on 655 consecutive patients with liver resection for colorectal cancer metastasis operated in our centre between April 1996 and March 2016. Preoperative, intraoperative, pathologic, and outcome data for patients undergoing liver resection for metastatic colorectal were examined. Univariate analysis followed by multivariate Cox regression analysis was performed in order to identify the risk factors associated with prognostic factors related to survival. Results: There were 371 men (56.65%) and 284 women (43.35%), with a median age of 60 year-old (range 24 to 84). The primary tumor location was colon in 454 cases (69.31%) and rectum for 201 cases (30.69%). Synchronous tumors were resected in 353 cases (53.72%). The surgical mortality rate was 2.95%. The 5-year survival rate was 29.2%, and the 10-year survival rate was 17.1%. Four factors were found to be significant independent predictors of poor long-term outcome by multivariate analysis: bilobar liver metastasis (p = 0.003) with HR 1.653 (95%CI 1.180-2.316), non-R0 resection (p < 0.001) with HR 6.066 (95%CI 3.508-10.489), N2 lymph node stage (p = 0.007) with HR 1.528 (95%CI 1.125-2.075) and lack of adjuvant chemotherapy (p = 0.046) with HR 1.703 (95%CI 1.009-2.873). Conclusion: The independent prognostic factors for poor OS were both clinico-pathologic and therapeutic. In patients with good prognostic factors, an appropriate onco-surgical treatment is able to significantly prolong survival. In patients with poor prognostic factors, prognosis is mainly influenced by tumor biology and the benefit from current therapies is still modest.
BJS Open, 2018
Background: Markers of tumour biology may be valuable prognostic indicators after hepatic resection of colorectal cancer liver metastases (CRLMs). Identification of the aggressiveness of these metastases might inform the appropriateness of hepatic surgery. Methods: Patients undergoing liver resection for CRLMs between January 2001 and July 2013 in four tertiary hospitals were reviewed. A mathematical model to estimate CRLM doubling times was constructed for patients with metachronous metastases. Tumour doubling time was investigated in relation to the features of colorectal cancer, including KRAS status. The hazard rate for recurrence and death following hepatectomy was explored through the Kernel-smoothed estimator. Results: Of 1063 patients undergoing liver resection for CRLMs, 361 with metachronous metastases undergoing single-stage hepatectomy were analysed. The mean doubling time in patients not receiving chemotherapy between surgery for colorectal cancer and CRLM was 71⋅4 days. Tumour doubling time was shorter in patients with more advanced primary tumour stages, with mutant KRAS and in those who did not receive chemotherapy. For fast-growing CRLMs (doubling time less than 48 days), the risk of recurrence was highest within the first postoperative year, and was about 7 per cent per month. Conclusion: Primary features of colorectal cancer were linked to aggressiveness of CRLMs as measured by doubling time.
Clinical & Experimental Metastasis, 2020
Adjuvant systemic chemotherapy (CTx) is widely administered in patients with colorectal liver metastases (CRLM). Histopathological growth patterns (HGPs) are an independent prognostic factor for survival after complete resection. This study evaluates whether HGPs can predict the effectiveness of adjuvant CTx in patients with resected CRLM. Two main types of HGPs can be distinguished; the desmoplastic type and the non-desmoplastic type. Uni- and multivariable analyses for overall survival (OS) and disease-free survival (DFS) were performed, in both patients treated with and without preoperative chemotherapy. A total of 1236 patients from two tertiary centers (Memorial Sloan Kettering Cancer Center, New York, USA; Erasmus MC Cancer Institute, Rotterdam, The Netherlands) were included (period 2000–2016). A total of 656 patients (53.1%) patients received preoperative chemotherapy. Adjuvant CTx was only associated with a superior OS in non-desmoplastic patients that had not been pretreat...
Liver International, 2009
Background: Patient outcome after resection of colorectal liver metastases can be predicted by various prognostic factors. Aims: Development of a model for risk stratification based on analysis of prognostic factors. Methods: Data of 201 patients were collected prospectively and included in a single-centre trial. A total of 20 factors were analysed as to their influence on recurrence-free and overall survival. Independent prognostic factors were entered into a model of a clinical risk score. Results: Median recurrence-free survival reached 24 months for all patients; median overall survival was 50 months. Only a synchronous manifestation of primary colorectal carcinoma and liver metastases, the presence of four or more metastases and a carcino-embryonic antigen level of 200 ng/ml or more significantly influenced recurrence-free and overall survival in the multivariate analysis. The derived risk stratification grouped the patients according to the following criteria: low risk, zero prognostic factors (n = 112); intermediate risk, one factor (n = 74); high risk, two or more factors (n = 15). The median recurrence-free survival for low, intermediate and high risk were 30.0, 23.0 and 11.0 months, respectively; the median overall survival was 94.0, 40.0 and 33.0 months. Compared with the low-risk group, patients with intermediate risk demonstrated an increased hazard ratio (HR) of 1.57-fold for recurrence (P = 0.018) and 1.91-fold for mortality (P = 0.007). For the high-risk group, the HR rose significantly to 3.26 for recurrence (P o 0.0005) and to 3.10 for mortality (P = 0.001). Conclusions: The presented clinical score may allow for patients with colorectal liver metastases to be stratified appropriately and for optimization of their subsequent therapeutic management. Patients with primary cancer of the colon UICC III had undergone intravenous fluorouracil-based adjuvant chemotherapy; patients with primary rectal cancer UICC II and III had undergone adjuvant radiation with 50.4 Gy and fluorouracil-based chemotherapy. Recently (in the last 3 years), all patients with rectal cancer stages UICC II and III received
Pathology - Research and Practice, 2019
Colorectal carcinoma (CRC) is one of the most common malignancies and a major cause of cancer-related death worldwide. The liver is the most frequent site of metastatic spread, so that about half of the patients with CRC have or develop liver metastases (LM) during the clinical course of the disease. Colorectal LM can potentially be cured by surgery, but most patients still experience disease progression and recurrence after the surgical treatment. Prediction of a patient's post-surgical clinical course is mainly based on clinical parameters or the histopathological features of the primary tumor, while little attention is given to the pathological characteristics of the LM. In this paper, we review the prognostic relevance of the gross and microscopic pathological features observed in surgically resected LM and propose which information should be included in the histopathological report to guide surgeons and oncologists for the subsequent therapeutic management.