BackgroundThe liver is a common metastatic site for a large variety of primary tumors. For both patients with known and unknown primary tumors it is important to understand metastatic patterns to provide tailored therapies.ObjectiveTo perform a nationwide exploration of the origins of histological confirmed liver metastases.ResultsA total of 23,154 patients were identified. The majority of liver metastases were carcinomas (n=21,400; 92%) of which adenocarcinoma was the most frequent subtype (n=17,349; 75%). Most common primary tumors in patients with adenocarcinoma were from colorectal (n=8,004), pancreatic (n=1,755) or breast origin (n=1,415). In women of 50 years and younger, metastatic adenocarcinoma originated more frequently from breast cancer, while in women older than 70 years liver metastases originated more frequently from gastrointestinal tumors. Liver metastases in men older than 70 years originated often from squamous cell lung carcinoma. An unknown primary tumor was detected in 4,209 (18%) patients, although tumor type could be determined in 3,855 (92%) of them.MethodsData were collected using the nationwide network and registry of histo- and cytopathology in the Netherlands (PALGA). All histological confirmed liver metastases between January 2001 and December 2010 were evaluated for tumor type, origin of the primary tumor and were correlated with patient characteristics (age, gender).ConclusionThe current study provides an overview of the origins of liver metastases in a series of 23,154 patients.

Histological reporting of hepatic resections of colorectal liver metastases (CRLMs) is limited to confirmation of diagnosis and evaluation of resection margins. More exhaustive diagnostic reporting might be warranted. Here, we critically and systematically review the potentially important histological prognostic factors in CRLM. Histological features such as intrahepatic spread, resection margins, and tumour response to neoadjuvant chemotherapy have been defined. Intrahepatic spread (venous, lymphatic, bile duct and perineural invasion) was evaluated in a number of studies. Meta-analysis demonstrated a clear correlation between 5-year overall survival and both portal vein invasion (RR 1.8, 95% CI 1.3-2.5) and lymphatic invasion (RR 1.7, 95% CI 1.4-2.0). The impact of hepatic vein invasion and bile duct invasion on outcome is not clear. Perineural invasion was linked to survival in one study. Resection margin is an important prognostic factor; however, the significance of the width of negative margins remains controversial. Various studies have evaluated tumour response to neoadjuvant chemotherapy, but different grading systems were used, and definite recommendations cannot be made. In conclusion, with the high incidence of CRLM and the increase in the number of hepatic resections, we need well-defined prognostic factors, studied in homogeneous patient populations, to optimize diagnostic work-up. This review identifies several of these factors.

BackgroundFor a selection of patients with colorectal liver metastases (CRLM), liver resection is a curative option. In order to predict long-term survival, clinicopathologic risk scores have been developed, but little is known about histologic factors and their prognostic value for disease-free and overall survival. The objective of the present study was to assess possible prognostic histologic factors in patients with solitary CRLM treated with liver resection who did not receive neoadjuvant treatment.MethodsPatients with solitary CRLM who underwent liver resection between 1992 and 2011 were evaluated for clinical prognostic factors. Histologic analyses on tumor thickness at the tumor–normal interface, presence of a fibrotic capsule, intrahepatic vascular invasion, lymphatic invasion, or bile duct invasion and perineural growth were performed, using immunohistochemistry.ResultsA total of 124 patients were analyzed with a median follow-up of 41 months (range 1–232 months). There was no association between histologic factors and disease-free survival in multivariate analysis. In multivariate analysis, intrahepatic lymphatic invasion was associated with a decreased overall survival (41.9 vs. 61.0 months; p = 0.041), especially in combination with vascular invasion (n = 15) (28.1 vs. 62.2 months; p < 0.0001). In addition, size over 50 mm (29.2 vs. 65.9 months; p = 0.004) and interval less than 12 months between resection of the primary tumor and diagnosis of liver metastasis (49.0 vs. 91.5 months: p = 0.019) were also independent adverse prognostic factors.ConclusionsIntrahepatic lymphatic invasion, especially in combination with vascular invasion, is an important adverse prognostic factor for overall survival in patients with solitary CRLM after liver resection.Electronic supplementary materialThe online version of this article (doi:10.1245/s10434-015-4562-8) contains supplementary material, which is available to authorized users.

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