Hepatocellular adenomas (HCA) are benign liver tumors that may transform into hepatocellular carcinoma (HCC), but the molecular drivers of this transformation remain ill-defined. This study evaluates ...the molecular changes in HCA and HCC and in comparison to their adjacent non-neoplastic liver.
11 patients with HCA and 10 patients with HCC without underlying hepatitis or cirrhosis were included in this pilot study. Tumor and non-tumor liver tissues were selected for immunohistochemical staining, small RNA sequencing, and targeted gene sequencing. We compared microRNA expressions and mutations between HCA and HCC and non-neoplastic liver.
HCA were classified as inflammatory (n = 6), steatotic (n = 4), or β-catenin activated (n = 1) subtypes. MicroRNA profile of all 3 HCA subtypes clustered between that of normal liver and HCC in principal component analysis. In both HCA and HCC, miR-200a, miR-429, and miR-490-3p were significantly downregulated compared to normal liver, whereas miR-452, miR-766, and miR-1180 were significantly upregulated. In addition, compared to HCA, HCC had significantly higher expression of members of the chromosome 19 miRNA cluster (C19MC), including miR-515-5p, miR-517a, miR-518b, and miR-520c-3p.
This study indicates that while there are significant differences in the molecular profile between HCA and HCC, several miRNAs are similarly deregulated in HCA and HCC compared to adjacent normal liver. These results may provide insights into the drivers of hepatocarcinogenesis and warrant further investigations.
The aim of the study was to evaluate outcomes after resection of colorectal liver metastases (CRLM) and concurrent extrahepatic disease (EHD), and to define prognostic factors.
There is increasing ...evidence to support resection of liver metastases and concurrent EHD in selected patients. Long-term survival data are lacking, and prognostic factors are not well defined.
Retrospective review of 219 patients was undertaken between January 1992 and December 2012, who underwent hepatectomy for CRLM and resection of synchronous EHD. Survival outcomes were estimated by the Kaplan-Meier method. Univariate and multivariate analyses of prognostic factors were performed. A scoring system for prognostication was developed.
The median, 3, 5, and 10-year overall survival were 34.4 months, 49%, 28%, and 10%, respectively. Disease recurred in 185 patients (90.2%) at a median of 8 months. There were 8 actual 10-year survivors. The site of EHD affected survival, with portal, retroperitoneal nodes and multiple sites associated with the worst prognoses. The size of the largest CRLM, the number of CRLM, unfavorable site of EHD, and progression of CRLM on neoadjuvant therapy were associated with overall survival on univariate and multivariate analyses. Three variables, assigned 1 point each, were used to create an EHD risk score: largest CRLM greater than 3 cm, greater than 5 CRLM, and unfavorable site of EHD. The resulting score was prognostic of overall and recurrence-free survival.
Long-term survival is possible after resection of liver metastases and concurrent EHD, but true cure is rare. A proposed scoring system may identify patients most likely to benefit from surgery.
Background
Reports show that FOLFIRINOX therapy for pancreatic ductal adenocarcinoma (PDAC) results in objective response rates two to threefold higher than those of other regimens. This study aimed ...to assess response and resection rates for locally unresectable (stage 3) patients initially treated with induction FOLFIRINOX.
Methods
The institutional cancer database was queried for patients treated with induction FOLFIRINOX therapy between 2010 and 2013. Patients were included in the study if they were treated at the authors’ institution for stage 3 PDAC (locally unresectable) that had been adjudicated at a weekly multidisciplinary tumor board.
Results
The study identified 101 patients. The median age was 64 years (range 37–81 years), and the median follow-up period was 12 months (range 3–37 months). The patients received a median of six cycles (range 1–20 cycles) of induction FOLFIRINOX. No grade 4 or 5 toxicity was recorded. At the initial restaging (median of 3 months after diagnosis), 23 patients (23 %) had developed distant metastases, 15 patients (15 %) had undergone resection, and 63 patients (63 %) had proceeded to chemoradiation. In the group of 63 patients who had proceeded to chemoradiation (median of 9 months after diagnosis), an additional 16 patients (16 %) had undergone resection, and 5 patients (5 %) had developed metastases. A partial radiographic response was observed in 29 % of all the patients, which was associated with ability to perform resection (
p
= 0.004). The median overall survival time was 11 months for the group that progressed with FOLFIRINOX and 26 months for the group that did not progress.
Conclusion
Nearly one third of the patients who had been initially identified as having stage 3 pancreatic carcinoma and had been treated with FOLFIRINOX responded radiographically and underwent tumor resection.
Microvascular invasion (MVI) is a significant risk factor for early recurrence after resection or transplantation for hepatocellular carcinoma (HCC). Knowledge of MVI status would help guide ...treatment recommendations, but is generally identified after operation. This study aims to predict MVI preoperatively using quantitative image analysis.
One hundred and twenty patients from 2 institutions underwent resection of HCC from 2003 to 2015 were included. The largest tumor from preoperative CT was subjected to quantitative image analysis, which uses an automated computer algorithm to capture regional variation in CT enhancement patterns. Quantitative imaging features by automatic analysis, qualitative radiographic descriptors by 2 radiologists, and preoperative clinical variables were included in multivariate analysis to predict histologic MVI.
Histologic MVI was identified in 19 (37%) patients with tumors ≤5 cm and 34 (49%) patients with tumors >5 cm. Among patients with tumors ≤5 cm, none of the clinical findings or radiographic descriptors were associated with MVI; however, quantitative features based on angle co-occurrence matrix predicted MVI with an area under curve of 0.80, positive predictive value of 63%, and negative predictive value of 85%. In patients with tumors >5 cm, higher α-fetoprotein level, larger tumor size, and viral hepatitis history were associated with MVI, and radiographic descriptors were not. However, a multivariate model combining α-fetoprotein, tumor size, hepatitis status, and quantitative feature based on local binary pattern predicted MVI with area under curve of 0.88, positive predictive value of 72%, and negative predictive value of 96%.
This study reveals the potential importance of quantitative image analysis as a predictor of MVI.
Background
Microwave (MWA) and radiofrequency ablation (RFA) are the most commonly used techniques for ablating colorectal-liver metastases (CRLM). The technical and oncologic differences between ...these modalities are unclear.
Methods
We conducted a matched-cohort analysis of patients undergoing open MWA or RFA for CRLM at a tertiary-care center between 2008 and 2011; the primary endpoint was ablation-site recurrence. Tumors were matched by size, clinical-risk score, and arterial-intrahepatic or systemic chemotherapy use. Outcomes were compared using conditional logistic regression and stratified log-rank test.
Results
We matched 254 tumors (127 per group) from 134 patients. MWA and RFA groups were comparable by age, gender, median number of tumors treated, proximity to major vessels, and postoperative complication rates. Patients in the MWA group had lower ablation-site recurrence rates (6% vs. 20%;
P
< 0.01). Median follow-up, however, was significantly shorter in the MWA group (18 months 95% confidence interval 17–20 vs. 31 months 95% confidence interval 28–35;
P
< 0.001). Kaplan–Meier estimates of ablation-site recurrence at 2 years were significantly lower for the lesions treated with MWA (7% vs. 18%,
P
: 0.01).
Conclusions
Ablation-site recurrences of CRLM were lower with MWA compared with RFA in this matched cohort analysis. Longer follow-up time in the MWA may increase the recurrence rate; however, actuarial local failure estimations demonstrated better local control with MWA.
Transarterial chemoembolization is accepted therapy for hepatocellular carcinoma (HCC). No randomized trial has demonstrated superiority of chemoembolization compared with embolization, and the role ...of chemotherapy remains unclear. This randomized trial compares the outcome of embolization using microspheres alone with chemoembolization using doxorubicin-eluting microspheres.
At a single tertiary referral center, patients with HCC were randomly assigned to embolization with microspheres alone (Bead Block BB) or loaded with doxorubicin 150 mg (LC Bead LCB). Random assignment was stratified by number of embolizations to complete treatment, and assignments were generated by permuted blocks in the institutional database. The primary end point was response according to RECIST 1.0 (Response Evaluation Criteria in Solid Tumors) using multiphase computed tomography 2 to 3 weeks post-treatment and then at quarterly intervals, with the reviewer blinded to treatment allocation. Secondary objectives included safety and tolerability, time to progression, progression-free survival, and overall survival. This trial is currently closed to accrual.
Between December 2007 and April 2012, 101 patients were randomly assigned: 51 to BB and 50 to LCB. Demographics were comparable: median age, 67 years; 77% male; and 22% Barcelona Clinic Liver Cancer stage A and 78% stage B or C. Adverse events occurred with similar frequency in both groups: BB, 19 of 51 patients (38%); LCB, 20 of 50 patients (40%; P = .48), with no difference in RECIST response: BB, 5.9% versus LCB, 6.0% (difference, -0.1%; 95% CI, -9% to 9%). Median PFS was 6.2 versus 2.8 months (hazard ratio, 1.36; 95% CI, 0.91 to 2.05; P = .11), and overall survival, 19.6 versus 20.8 months (hazard ratio, 1.11; 95% CI, 0.71 to 1.76; P = .64) for BB and LCB, respectively.
There was no apparent difference between the treatment arms. These results challenge the use of doxorubicin-eluting beads for chemoembolization of HCC.
Background Published prognostic models for overall survival after liver resection for intrahepatic cholangiocarcinoma require external validation before use in clinical practice. Study Design From ...January 1993 to May 2013, consecutive patients who underwent resection of intrahepatic cholangiocarcinoma were identified from a prospective database. The Wang nomogram was derived in an Asian cohort (n = 367) and included clinicopathologic variables and preoperative CEA and cancer antigen 19-9 levels. The Hyder nomogram was derived in an Eastern and Western multicenter cohort (n = 514) using clinicopathologic variables only. The AJCC Cancer Staging System (7th ed) and the preoperative Fudan risk score were also evaluated. Prognostic performance was assessed in terms of discrimination, calibration, and stratification. Results One hundred and eighty-eight patients were included, with a median follow-up of 41 months. Median overall survival was 48.7 months and estimated 3-year and 5-year overall survival rates were 59% and 45%, respectively. Overall survival prediction accuracy, according to concordance-index calculation, was 0.72 with the Wang nomogram, 0.66 with the Hyder nomogram, 0.63 with the AJCC system, and 0.55 using the Fudan score. Both nomograms provided effective patient stratification in distinct survival groups. Conclusions Both the Wang and Hyder nomograms provided accurate patient prognosis estimation after liver resection for intrahepatic cholangiocarcinoma and can be useful for decision making about adjuvant therapy. The Wang nomogram appears to be more appropriate in patients undergoing formal portal lymphadenectomy and requires preoperative CEA and cancer antigen 19-9 levels for optimal performance.
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