To determine the impact of RAS mutation status on the traditional clinical score (t-CS) to predict survival after resection of colorectal liver metastases (CLM).
The t-CS relies on the following ...factors: primary tumor nodal status, disease-free interval, number and size of CLM, and carcinoembryonic antigen level. We hypothesized that the addition of RAS mutation status could create a modified clinical score (m-CS) that would outperform the t-CS.
Patients who underwent resection of CLM from 2005 through 2013 and had RAS mutation status and t-CS factors available were included. Multivariate analysis was used to identify prognostic factors to include in the m-CS. Log-rank survival analyses were used to compare the t-CS and the m-CS. The m-CS was validated in an international multicenter cohort of 608 patients.
A total of 564 patients were eligible for analysis. RAS mutation was detected in 205 (36.3%) of patients. On multivariate analysis, RAS mutation was associated with poor overall survival, as were positive primary tumor lymph node status and diameter of the largest liver metastasis >50 mm. Each factor was assigned 1 point to produce a m-CS. The m-CS accurately stratified patients by overall and recurrence-free survival in both the initial patient series and validation cohort, whereas the t-CS did not.
Modifying the t-CS by replacing disease-free interval, number of metastases, and CEA level with RAS mutation status produced an m-CS that outperformed the t-CS. The m-CS is therefore a simple validated tool that predicts survival after resection of CLM.
Distal bile duct cholangiocarcinoma, ampullary adenocarcinoma, duodenal carcinoma, and ductal adenocarcinoma (PDAC) of the head of the pancreas usually have similar clinical presentation since they ...arise in the same circumscribed anatomical area, within 2 cm of the major duodenal papilla ....
Background
The past 20 years have seen advances in colorectal cancer management. We sought to determine whether survival in patients undergoing resection of colorectal liver metastases (CLM) has ...improved in association with three landmark advances: introduction of irinotecan- and/or oxaliplatin-containing regimens, molecular targeted therapy, and multigene alteration testing.
Methods
Patients undergoing CLM resection during 1998–2014 were identified and grouped by resection year. The influence of alterations in
RAS
,
TP53
, and
SMAD4
was evaluated and validated in an external cohort including patients with unresectable metastatic colorectal cancer.
Results
Of 1961 patients, 1599 met the inclusion criteria. Irinotecan- and/or oxaliplatin-containing regimens and molecular targeted therapy were used for more than 50% of patients starting in 2001 and starting in 2006, respectively, so patients were grouped as undergoing resection during 1998–2000, 2001–2005, or 2006–2014. Liver resectability indications expanded over time. The 5-year overall survival (OS) rate was significantly better in 2006–2014, vs. 2001–2005 (56.5% vs. 44.1%,
P
< 0.001).
RAS
alteration was associated with worse 5-year OS than
RAS
wild-type (44.8% vs. 63.3%,
P
< 0.001). However, OS did not differ significantly between patients with
RAS
alteration and wild-type
TP53
and
SMAD4
and patients with
RAS
wild-type in our cohort (
P
= 0.899) or the external cohort (
P
= 0.932). Of 312 patients with genetic sequencing data, 178 (57.1%) had clinically actionable alterations.
Conclusion
OS after CLM resection has improved with advances in medical therapy and surgical technique. Multigene alteration testing is useful for prognostication and identification of potential therapeutic targets.
Background. To assess the efficacy of intraoperative ultrasound (IOUS) compared with liver-specific magnetic resonance imaging (MRI) in patients with colorectal liver metastases (CRLMs). Methods. ...From January 2010 to December 2017, 721 patients underwent MRI as a part of preoperative workup within 1 month before hepatectomy and were considered for the study. Early intrahepatic recurrence (relapse at cut surface excluded) was assessed 6 months after the resection and was considered as residual disease undetected by IOUS and/or MRI. IOUS and MRI performance was compared on a patient-by-patient basis. Long-term results were also studied. Results. A total of 2845 CRLMs were detected by MRI, and the median number of CRLMs per patient was 2 (1–31). Preoperative chemotherapy was administered in 489 patients (67.8%). In 177 patients, 379 new nodules were intraoperatively found and resected. Among 379 newly identified nodules, 317 were histologically proven CRLMs (11.1% of entire series). The median size of new CRLMs was 6 ± 2.5 mm. Relationships between intrahepatic vessels and tumors differed between IOUS and MRI in 128 patients (17.7%). The preoperative surgical plan was intraoperatively changed for 171 patients (23.7%). Overall, early intrahepatic recurrence occurred in 8.7% of cases. To assess the diagnostic performance, 24 (3.3%) recurrences at the cut surface were excluded; thus, 5.4% of early relapses were considered for analysis. The sensitivity of IOUS was superior to MRI (94.5% vs 75.1%), while the specificity was similar (95.7% vs 95.9%). Multivariate analysis at the hepatic dome or subglissonian and mucinous histology revealed predictive factors of metastases missing at MRI. The 5-year OS (52.1% vs 37.8%, p=0.006) and DF survival (45.1% vs 33%, p=0.002) were significantly worse among patients with new CRLMs than without. Conclusions. IOUS improves staging in patients undergoing resection for CRLMs even in the era of liver-specific MRI. Intraoperative detection of new CRLMs negatively affects oncologic outcomes.
Most studies predicting survival after resection, transarterial chemoembolization (TACE), and ablation analyzed diameter and number of hepatocellular carcinomas (HCCs) as dichotomous variables, ...resulting in an underestimation of risk variation. We aimed to develop and validate a new prognostic model for patients with HCC using largest diameter and number of HCCs as continuous variables.
The prognostic model was developed using data from patients undergoing resection, TACE, and ablation in 645 Japanese institutions. The model results were shown after balanced using the inverse probability of treatment-weighted analysis and were externally validated in an international multi-institution cohort.
Of 77,268 patients, 43,904 patients, including 15,313 (34.9%) undergoing liver resection, 13,375 (30.5%) undergoing TACE, and 15,216 (34.7%) undergoing ablation, met the inclusion criteria. Our model (http://www.u-tokyo-hbp-transplant-surgery.jp/about/calculation.html) showed that the 5-year overall survival (OS) in patients with HCC undergoing these procedures decreased with progressive incremental increases in diameter and number of HCCs. For patients undergoing resection, the inverse probability of treatment-weighted-adjusted 5-year OS probabilities were 10%-20% higher compared with patients undergoing TACE for 1-6 HCC lesions <10 cm and were also 10%-20% higher compared with patients undergoing ablation when the HCC diameter was 2-3 cm. For patients undergoing resection and TACE, the model performed well in the external cohort.
Our novel prognostic model performed well in predicting OS after resection and TACE for HCC and demonstrated that resection may have a survival benefit over TACE and ablation based on the diameter and number of HCCs.
Background. Mirizzi syndrome is a condition difficult to diagnose and treat, representing a particular “challenge” for the biliary surgeon. The disease can mimic cancer of the gallbladder, causing ...considerable diagnostic difficulties. Furthermore, it increases the risk of intraoperative biliary injury during cholecystectomy. The aim of this study is to point out some particular aspects of diagnosis and treatment of this condition. Methods. The clinical records of patients with Mirizzi syndrome, treated in the last five years, were reviewed. Clinical data, cholangiograms, preoperative diagnosis, operative procedures, and early and late results were examined. Results. Eighteen consecutive patients were treated in the last five years. Presenting symptoms were jaundice, pain, and cholangitis. Preoperative diagnosis of Mirizzi syndrome was achieved in 11 patients, while 6 had a diagnosis of gallbladder cancer and 1 of Klatskin tumor. Seventeen patients underwent surgery, including cholecystectomy in 8 cases, bile duct repair over T-tube in 3 cases, and hepaticojejunostomy in 4 cases. Two cases (11.1%) of gallbladder cancer associated with the Mirizzi syndrome were incidentally found: a patient underwent right hepatectomy and another patient was unresectable. The overall morbidity rate was 16.6%. There was no postoperative mortality. An ERCP with stent insertion was required in three cases after surgery. Sixteen patients were asymptomatic at a mean distance of 24 months (range: 6-48) after surgery. Conclusions. Mirizzi syndrome requires being treated by an experienced biliary surgeon after a careful assessment of the local situation and anatomy. The preoperative placement of a stent via ERCP can simplify the surgical procedure.
In patients with hepatocellular carcinoma (HCC), liver resection is potentially curative. Nevertheless, post-operative recurrence is common, occurring in up to 70% of patients. Factors traditionally ...recognized to predict recurrence and survival after liver resection for HCC include pathologic factors (i.e., microvascular and capsular invasion) and an increase in alpha-fetoprotein level. During the past decade, many new markers have been reported to correlate with prognosis after resection of HCC: liquid biopsy markers, gene signatures, inflammation markers, and other biomarkers, including PIVKA-II, immune checkpoint molecules, and proteins in urinary exosomes. However, not all of these new markers are readily available in clinical practice, and their reproducibility is unclear. Liquid biopsy is a powerful and established tool for predicting long-term outcomes after resection of HCC; the main limitation of liquid biopsy is represented by the cost related to its technical implementation. Numerous patterns of genetic expression capable of predicting survival after curative-intent hepatectomy for HCC have been identified, but published findings regarding these markers are heterogenous. Inflammation markers in the form of prognostic nutritional index and different blood cell ratios seem more easily reproducible and more affordable on a large scale than other emerging markers. To select the most effective treatment for patients with HCC, it is crucial that the scientific community validate new predictive markers for recurrence and survival after resection that are reliable and widely reproducible. More reports from Western countries are necessary to corroborate the evidence.
Background
Non-anatomic resection (NAR) has emerged as a safe and effective technique for resection of colorectal liver metastases (CRLM). More recently,
RAS
mutation has been identified as an ...important indicator of aggressive disease, which may require anatomic resection (AR). In this retrospective study, we compared the long-term outcomes of AR versus NAR in CRLM patients with and without
RAS
mutations.
Methods
Patients with known
RAS
mutation status who underwent AR or NAR for CRLM between 2006 and 2016 were included. Differences in baseline characteristics were adjusted using 1:1 propensity score matching, including the most important factors that contributed to the decision to use the resection technique. Overall survival (OS), recurrence-free survival (RFS), and liver-specific recurrence-free survival (L-RFS) were compared between cohorts.
Results
Among 622 total patients, 338 (54%) underwent AR and 284 (46%) NAR. There was no difference in OS or L-RFS between the AR and NAR groups, regardless of mutation status. There was increased RFS in the
RAS
WT patients with NAR (
P
= 0.034), but no difference in RFS in the whole cohort or
RAS
mutant group. After propensity score matching, 360 patients were analyzed, and no differences in OS, RFS, or L-RFS rates were seen between any groups. There was also no difference in margin recurrence.
Conclusions
Similar outcomes can be achieved with both AR and NAR, regardless of
RAS
mutation status. These data do not support a universal requirement for AR in
RAS
mutant CRLM when not necessary to achieve an R0 resection.
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