Can the presence of KRAS mutations guide the type of liver resection during simultaneous resection of colorectal liver metastasis?

Can the Presence of KRAS Mutation Be a Judge to Determine the Resection Type of Colorectal Liver Metastasis?

To investigate the potential clinical advantage of anatomical resection versus nonanatomical resection for colorectal liver metastases, according to KRAS mutational status. KRAS-mutated colorectal liver metastases (CRLM) are known to be more aggressive than KRAS wild-type tumors. Although nonanatomical liver resections have been demonstrated as a viable approach for CRLM patients with similar oncologic outcomes to anatomical resections, this may not be the case for the subset of KRAS-mutated CRLM. 389 patients who underwent hepatic resection of CRLM with known KRAS mutational status were identified. Survival estimates were calculated using the Kaplan-Meier method, and multivariable analysis was conducted using the Cox proportional hazards regression model. In this study, 165 patients (42.4%) underwent nonanatomical resections and 140 (36.0%) presented with KRAS-mutated CRLM. Median disease-free survival (DFS) in the entire cohort was 21.3 months, whereas 1-, 3-, and 5-year DFS was 67.3%, 34.9%, and 31.5% respectively. Although there was no difference in DFS between anatomical and nonanatomical resections in patients with KRAS wild-type tumors (P = 0.142), a significant difference in favor of anatomical resection was observed in patients with a KRAS mutation (10.5 vs. 33.8 months; P < 0.001). Five-year DFS was only 14.4% in the nonanatomically resected group, versus 46.4% in the anatomically resected group. This observation persisted in multivariable analysis (hazard ratio: 0.45; 95% confidence interval: 0.27-0.74; P = 0.002), when corrected for number of tumors, bilobar disease, and intraoperative ablations. Nonanatomical tissue-sparing hepatectomies are associated with worse DFS in patients with KRAS-mutated tumors. Because of the aggressive nature of KRAS-mutated CRLM, more extensive anatomical hepatectomies may be warranted.

Anatomical resection (AR) for colorectal liver metastasis (CLM) is disputable. We investigated the impact of AR on short-term outcomes and survival in CLM patients. Patients having hepatectomy with AR or nonanatomical resection (NAR) for CLM were reviewed. Comparison was made between AR and NAR groups. Group comparison was performed again after propensity score matching with ratio 1:1. AR group (n = 234 vs n = 89 in NAR group) had higher carcinoembryonic antigen level (20 vs 7.8ng/mL, p ≤ 0.001), more blood loss (0.65 vs 0.2 L, p < 0.001), more transfusions (19.2% vs 3.4%, p = 0.001), longer operation (339.5 vs 180min, p < 0.001), longer hospital stay (9 vs 6days, p < 0.001), more tumors (p < 0.001), larger tumors (4 vs 2cm, p < 0.001), more bilobar involvement (20.9% vs 7.9%, p = 0.006), and comparable survival (overall, p = 0.721; disease-free, p = 0.695). After propensity score matching, each group had 70 patients, with matched tumor number, tumor size, liver function, and tumor marker. AR group had more open resections (85.7% vs 68.6%, p = 0.016), more blood loss (0.556 vs 0.3 L, p = 0.001), more transfusions (17.1% vs 4.3%, p = 0.015), longer operation (310 vs 180min, p < 0.001), longer hospital stay (8.5 vs 6days, p = 0.002), comparable overall survival (p = 0.819), and comparable disease-free survival (p = 0.855). Similar disease-free survival and overall survival of CLM patients were seen with the use of AR and NAR. However, AR may entail a more eventful postoperative course. NAR with margin should be considered whenever feasible.

This study aimed to investigate the impact of non-anatomical liver resection (NAR) versus anatomical resection (AR) in patients with colorectal liver metastasis (CRLM), with regard to perioperative and long-term outcomes. Analysis of prospectively collected data for patients with CRLM who underwent either AR or NAR between January 1993 and August 2011 was performed. The impact of AR and NAR on morbidity, mortality, margin positivity, redo liver resections, overall survival (OS) and disease free survival (DFS) was analysed. A total of 1574 resections for CRLM were performed. A total of 249 were redo resections and 334 patients underwent combined AR and NAR, hence, 583 were excluded. In total, 582 AR and 409 NAR were performed. The median age was 66 years (range 23.8-91.8). Median follow up was 32.2 months (interquartile range 17.5-56.9). The need for postoperative transfusion (11.6% versus 2.2%, P = <0.0001), overall complications (25% versus 10.7%, P < 0.0001) and 90-day mortality (4.9% versus 1.2%, P < 0.0001) was higher in the AR group. R0 and R1 resection rates (AR 26.2% NAR 25%, P = 0.69) and number of patients with intrahepatic recurrence was similar between the two groups (AR 17.5% NAR 22%, P = 0.08). However, the need for redo liver surgery was higher in NAR group 15.4% versus 8.7% (P < 0.001). The OS (NAR 34.1 months versus AR 31.4 months, P = 0.002) and DFS were longer in the NAR group (NAR 18.8 months versus AR 16.9 months, P = 0.031). A parenchymal preserving surgery (NAR) is associated with lower complication rates and better OS and DFS when compared with AR without compromising margin status. However, NAR increases the need for repeat liver resections.

BackgroundThere are concerns that non‐anatomical resection (NAR) worsens perioperative and oncological outcomes compared with those following anatomical resection (AR) for colorectal liver metastases (CRLM). Most previous studies have been biased by the effect of tumour size. The aim of this study was to compare oncological outcomes after NAR versus AR.MethodsThis was a retrospective study of consecutive patients who underwent CRLM resection with curative intent from 1999 to 2016. Data were retrieved from a prospectively developed database. Survival and perioperative outcomes for NAR and AR were compared using propensity score analyses.ResultsSome 358 patients were included in the study. Median follow‐up was 34 (i.q.r. 16–68) months. NAR was associated with significantly less morbidity compared with AR (31·1 versus 44·4 per cent respectively; P = 0·037). Larger (hazard ratio (HR) for lesions 5 cm or greater 1·81, 95 per cent c.i. 1·13 to 2·90; P = 0·035) or multiple (HR 1·48, 1·03 to 2·12; P = 0·035) metastases were associated with poor overall survival (OS). Synchronous (HR 1·33, 1·01 to 1·77; P = 0·045) and multiple (HR 1·51, 1·14 to 2·00; P = 0·004) liver metastases, major complications after liver resection (HR 1·49, 1·05 to 2·11; P = 0·026) or complications after resection of the primary colorectal tumour (HR 1·51, 1·01 to 2·26; P = 0·045) were associated with poor disease‐free survival (DFS). AR was prognostic for poor OS only in tumours smaller than 30 mm, and R1 margin status was not prognostic for either OS or DFS. NAR was associated with a higher rate of salvage resection than AR following intrahepatic recurrence.ConclusionsNAR has at least equivalent oncological outcomes to AR while proving to be safer. NAR should therefore be the primary surgical approach to CRLM, especially for lesions smaller than 30 mm.

BACKGROUNDThe long-term survival of patients with solitary hepatocellular carcinoma (HCC) following anatomical resection (AR) vs non-anatomical resection (NAR) is still controversial. It is necessary to investigate which approach is better for patients with solitary HCC.AIMTo compare perioperative and long-term survival outcomes of AR and NAR for solitary HCC.METHODSWe performed a comprehensive literature search of PubMed, Medline (Ovid), Embase (Ovid), and Cochrane Library. Participants of any age and sex, who underwent liver resection, were considered following the following criteria: (1) Studies reporting AR vs NAR liver resection; (2) Studies focused on primary HCC with a solitary tumor; (3) Studies reporting the long-term survival outcomes (> 5 years); and (4) Studies including patients without history of preoperative treatment. The main results were overall survival (OS) and disease-free survival (DFS). Perioperative outcomes were also compared.RESULTSA total of 14 studies, published between 2001 and 2020, were included in our meta-analysis, including 9444 patients who were mainly from China, Japan, and Korea. AR was performed on 4260 (44.8%) patients. The synthetic results showed that the 5-year OS [odds ratio (OR): 1.19; P < 0.001] and DFS (OR: 1.26; P < 0.001) were significantly better in the AR group than in the NAR group. AR was associated with longer operating time [mean difference (MD): 47.08; P < 0.001], more blood loss (MD: 169.29; P = 0.001), and wider surgical margin (MD = 1.35; P = 0.04) compared to NAR. There was no obvious difference in blood transfusion ratio (OR: 1.16; P = 0.65) or postoperative complications (OR: 1.24, P = 0.18).CONCLUSIONAR is superior to NAR in terms of long-term outcomes. Thus, AR can be recommended as a reasonable surgical option in patients with solitary HCC.

597P - Meta-analysis of KRAS mutation as prognostic factor in patients (pts) with resection of colorectal (CRC) liver metastases: Tumour burden and Sidedness analysis

To evaluate the prognostic impact of anatomic versus nonanatomic resection on the patients' survival after resection of a single hepatocellular carcinoma (HCC). Anatomic resection is a reasonable treatment option for HCC; however, its clinical significance remains to be confirmed. Curative hepatic resection was performed for a single HCC in 210 patients; the patients were classified into the anatomic resection (n = 156) and nonanatomic resection (n = 54) groups. In 84 patients assigned to the anatomic resection group, segmentectomy or subsegmentectomy was performed. We evaluated the outcome of anatomic resection, including segmentectomy and subsegmentectomy, in comparison with that of nonanatomic resection, by the multivariate analysis taking into consideration 14 other clinical factors. Both the 5-year overall survival and disease-free survival rates in the anatomic resection group were significantly better than those in the nonanatomic resection group (66% versus 35%, P = 0.01, and 34% versus 16%, P = 0.006, respectively). In the segmentectomy and subsegmentectomy group, the 5-year overall and disease-free survival rates were 67% and 28%, respectively, both of which were also higher than the corresponding rates in the nonanatomic resection group (P = 0.007 and P = 0.001, respectively). The results of multivariate analysis revealed that anatomic resection was a significantly favorable factor for overall and disease-free survivals: the hazard ratios were 0.57 (95% confidence interval, 0.32-0.99, P= 0.04), and 0.65 (0.43-0.96, P = 0.03). Anatomic resection for a single HCC yields more favorable results rather than nonanatomic resection.

The Role of Peri-operative Chemotherapy for Resectable Colorectal Liver Metastasis: What Does the Evidence Support?

Clinical significance and prognostic relevance of KRAS, BRAF, PI3K and TP53 genetic mutation analysis for resectable and unresectable colorectal liver metastases: A systematic review of the current evidence

Background: The relative benefit of anatomical resection (AR) versus non-anatomical resection (NAR) in hepatocellular carcinoma (HCC) remains controversial. This study compared the survival outcomes and recurrence rates of HCCs analysed according to tumour size and the extent of resection. Methods: Consecutive patients with HCC who underwent curative resection at Asan Medical Center between January 1999 and December 2009 were included in this study. We performed propensity score matching (PSM) according to tumour size to compare the survival outcomes between AR and NAR. A total of 986 patients were analysed; 812 and 174 patients underwent AR and NAR, respectively. Results: Before PSM, regardless of tumour size, the AR group demonstrated significantly better 5-year overall survival (OS) and recurrence-free survival (RFS) than the NAR group (p < 0.001). After PSM, the AR group demonstrated better OS and RFS rates than the NAR group when tumour size was less than 5 cm, but there was no significant difference in the OS and RFS rates between the two groups when tumour size was equal to or greater than 5 cm. In tumours less than 5 cm in size, AR was the most significant factor associated with OS and RFS. However, this prognostic effect of AR was not demonstrated in tumours with sizes equal to or greater than 5 cm. Conclusion: In patients with HCCs smaller than 5 cm, AR reduced the risk of tumour recurrence and improved OS. In HCCs larger than 5 cm, AR and NAR showed comparable survival outcomes.

Impact of anatomical liver resection on patient survival in KRAS-wild-type colorectal liver metastasis: A multicenter retrospective study

Anatomic resection (AR) is widely performed for hepatocellular carcinoma (HCC), but it is generally not considered superior to non-anatomic resection (NAR) in terms of prognosis. So we compared the prognosis of AR with that of NAR for HCC. We searched for articles about AR versus NAR for HCC published between January 1998 and December 2018 in PubMed, Cochrane Library, EMBASE and Wanfang database. Meta-analysis was performed on patient characteristics, tumor characteristics, operative characteristics, perioperative outcomes and long-term outcomes. A total of 38 studies involving 9122 patients were included: 5062 were in the AR group and 4060 in the NAR group. Only one study included in our meta-analysis was randomized controlled trial, and others were comparative cohort studies. The AR group had an advantage over NAR group in the aspect of age, liver cirrhosis level and liver reserve function; but had a disadvantage in the aspect of tumor size, AFP level, operation time, blood loss, microvascular invasion, pathological differentiation and postoperative complication. The AR group gained 1-, 3-, and 5-year overall survival (OS) and disease-free survival (DFS) benefits versus NAR group, but there was significant heterogeneity between groups in terms of patient and tumor characteristics. AR is superior to NAR regarding the long-term outcomes considering the relatively acceptable heterogeneity. More prospective randomized controlled trials are required to further confirm the actual effect of AR or NAR on survival for HCC with less heterogeneity.

Background and Objectives: The survival benefit of anatomical liver resection for hepatocellular carcinoma has not been elucidated yet. In this study, we aimed to investigate the effects of anatomic and non-anatomic liver resection on surgical outcomes in patients with hepatocellular carcinoma. Materials and Methods: A retrospective analysis of patients undergoing anatomic or non-anatomic resections due to hepatocellular carcinoma between March 2006 and October 2019 was conducted. Demographics, preoperative laboratory assessments, treatment strategies, and postoperative outcomes were analyzed. Results: The total cohort consisted of 94 patients, with a mean age of 63.1 ± 8.9 years, and 74.5% were male. A total of 41 patients underwent anatomic liver resection, and 53 patients underwent non-anatomic resection. The overall survival rates were found to be similar (5-year overall survival was 49.3% for anatomic resection and 44.5% for non-anatomic resection). Estimated median overall survival times were 58.5 months and 57.3 months, respectively (p = 0.777). Recurrence-free 1-, 3-, and 5-year survival rates were found to be 73.6%, 39.1%, and 32.8% in the non-anatomic resection group and 48.8%, 22.7%, and 22.7% in the anatomic resection group, respectively. Grade three or higher complication rates were found to be similar among the groups. Conclusions: This study did not find a difference between two surgical methods, in terms of survival. A tailored selection of the resection method should be made, with the aim of complete removal of tumoral lesions and leaving a suitable functional liver reserve, according to the parenchymal quality and volume of the liver remnant.

Parenchymal-sparing hepatectomy (PSH) is recommended in patients with colorectal liver metastases (CRLM). Based on the principle of PSH, to investigate the impact of anatomical resection (AR) and non-anatomic resection (NAR) on the outcome of CRLM and to evaluate the potential prognostic impact of three peritumoral imaging features. Fifty-six patients who had abdominal gadoxetic acid-enhanced magnetic resonance imaging (MRI) before CRLM surgery were included in this retrospective research. Peritumoral early enhancement, peritumoral hypointensity on hepatobiliary phase (HBP), and biliary dilatation to the CRLM at MRI were evaluated. Survival estimates were calculated using the Kaplan-Meier method, and multivariate analysis was conducted to identify independent predictors of liver recurrence-free survival (LRFS), recurrence-free survival (RFS) and overall survival (OS). NAR had a lower 3-year LRFS compared with AR (36.6% vs. 78.6%, p = 0.012). No significant differences were found in 3-year RFS (34.1% vs. 41.7%) and OS (61.7% vs. 81.3%) (p > 0.05). In NAR group, peritumoral early enhancement was associated with poor LRFS (p = < 0.001, hazard ratio [HR] = 6.260; 95% confidence interval [CI], 2.322,16.876]) and poor RFS (p = 0.035, HR =2.516; 95% CI, 1.069,5.919). No independent predictors of CRLM were identified in the AR group. In patients with CRLM, peritumoral early enhancement was a predictor of LRFS and RFS after NAR according to the principle of PSH.