ABSTRACT: : Upon colon cancer metastasis resection in liver, disease outcome is heterogeneous, ranging from indolent to very aggressive, with early recurrence. The aim of this study is to investigate the capability of metastasis associated in colon cancer 1 (MACC1) levels measured in liver metastasis specimens to predict further recurrence of the disease.
: Gene expression and gene dosage of MACC1, hepatocyte growth factor (HGF), and hepatocyte growth factor receptor (MET) were assessed using quantitative realtime polymerase chain reaction on a cohort of 64 liver metastasis samples from patients with complete follow-up of 36 months and detailed clinical annotation. The most relevant mutations associated to prognosis in colorectal cancer, KRAS, and PIK3CA were assessed on the same specimens with Sanger sequencing.
: Receiver operating characteristic (ROC) analysis revealed that MACC1 mRNA abundance is a good indicator of metastatic recurrence (AUC = 0.65, P < 0.05), whereas no such results were obtained with MET and HGF, nor with gene dosage. Generation of MACC1-based risk classes was capable of successfully separating patients into poor and good prognosis subgroups [hazard ratio (HR) = 5.236, 95% confidence interval (CI) = 1.2068-22.715, P < 0.05]. Also KRAS mutation was significantly associated with higher risk of recurrence (HR = 2.07, 95% CI = 1.048-4.09, P < 0.05). Cox regression multivariate analysis supported the independence of MACC1, but not KRAS, from known prognostic clinical information (Node Size HR = 3.155, 95% CI = 1.4418-6.905, P < 0.001, Preoperative carcinoembryonic antigen HR = 2.359, 95% CI = 1.0203-5.452, P < 0.05, MACC1 HR = 7.2739, 95% CI = 1.6584-31.905, P < 0.01).
: MACC1, a new easily detectable biomarker in cancer, is an independent prognostic factor of recurrence after liver resection of colorectal cancer metastasis.
Annals of surgery 06/2013; 257(6):1089-95. · 7.90 Impact Factor
ABSTRACT: The aim of the present study is to examine the effect of systemic chemotherapy after the 1st-stage hepatectomy (CT×2) on the progression of disease and dropout rates. A major pitfall of the 2-stage hepatectomy procedure is a high dropout rate after the 1st-stage hepatectomy due to progression of disease (PD). Routine use of CT×2 has been advocated.
A total of 47 patients with multiple, bilateral unresectable liver metastases were selected for a 2-stage hepatectomy procedure (±portal vein occlusion).
Of the total, 37 patients (78.7%) underwent systemic chemotherapy before the 1st-stage hepatectomy (CT×1) and 25 patients (53.2%) underwent CT×2; PD was significantly more common during CT×2 than during CT×1 (P=.002). Of the 47 patients planned for the 2nd-stage hepatectomy, 36 (76.6%) completed the procedure. Of these 47 patients, 25 (53.2%) showed PD after the 1st-stage hepatectomy, 12 in the CT×2 group and 13 in the no-CT×2 group; administration of CT×2 did not significantly affect the PD rate (P=.561). The overall dropout rate was 23.4% (n=11 patients): 16% in the CT×2 group vs. 31.8% in the no-CT×2 group (P=.303).
The routine use of chemotherapy between the 1st- and 2nd-stage hepatectomy does not guarantee lower PD and dropout rates.
Annals of Surgical Oncology 09/2011; 19(4):1310-5. · 4.17 Impact Factor
ABSTRACT: Optimal margin width is uncertain because of conflicting results from recent studies using overall survival as the end-point. After recurrence, re-resection and aggressive chemotherapy heavily affect survival time; the potential confounding effect of such factors has not been investigated. Use of recurrence-free survival (RFS) may overcome this limitation. The aim of this study is to evaluate the impact of width of resection margin on RFS and site of recurrence after hepatic resection for colorectal metastases (CRM).
From a prospectively maintained institutional database (1/1999-12/2007) we identified 314 patients undergone hepatectomy for CRM (1/1999-12/2007) with detailed pathologic analysis of the surgical margin and complete follow-up imaging studies documenting disease status and site of recurrence, which was categorized as: resection margin (M(arg)), other intra-hepatic ((other)IH), lung (L) or other extra-hepatic ((other)EH). Recurrence-free estimation was the survival end-point.
Median follow-up was 56.5 months. Two hundred and fifteen patients (68.8%) recurred at 288 sites after a mean of 15.5 months. A positive resection margin was associated with an increased risk of M(arg) recurrence (P < 0.001). The presence of >or=2 metastases was the only factor increasing the risk of positive margins (P < 0.05). The width of the negative resection margin (>or=1 cm versus >1 cm) was not a prognostic factor of worse RFS (30.2% versus 37.3%, P = 0.6). Node status of the primary tumour, and size and number of CRM were independent predictors of RFS.
Tumour biology and not the width of the negative resection margin affect RFS.
Annals of Surgical Oncology 10/2009; 17(5):1324-9. · 4.17 Impact Factor
ABSTRACT: The prognostic significance of variables related to nodal involvement (node status, number of disease-positive nodes [posNn], node ratio [Nr], and site of nodal metastases) in patients with resected pancreatic head cancer remains poorly defined.
Clinical, operative, and pathologic data, including indexes of the burden and extent of nodal involvement, were analyzed in a consecutive series of 77 patients who underwent resection with extended lymphadenectomy for adenocarcinoma of the pancreatic head.
Fifty-nine patients (77%) were found to have lymph node (LN) metastases. Median LN count, posNn, and Nr were 28 (10-54), 4 (1-29), and 14% (2%-55%), respectively. Twenty-six patients (44% of N1) had metastases limited to node level (NL) 1 (i.e., peripancreatic nodes); metastases up to NL2 (nodes along main arteries and hepatic hilum) and NL3 (preaortic nodes) were found in 21 (36%) and 12 (20%) patients, respectively. Interestingly, survival of patients with positive LN limited to NL1 was similar to that of node-negative patients (P = 0.407). posNn, Nr, and NL were all significant predictors of survival (P < 0.015). posNn and Nr proved to be an accurate proxy of NL involvement. The best cutoff of posNn was 2 and of and Nr was 10%.
The level of nodal metastatic spread is a statistically significant prognostic factor in cancer of the pancreatic head. Both posNn and Nr are accurate proxy of NL and may improve patients' risk stratification.
Annals of Surgical Oncology 09/2009; 16(12):3323-32. · 4.17 Impact Factor