Synchronous Colorectal Cancer Liver Metastases Research Articles

Clinical study on simultaneous resection of liver metastases combined with hyperthermic intraperitoneal chemotherapy for synchronous colorectal cancer liver metastasis

PurposeThis study aimed to analyze the clinical effect of simultaneous resection of liver metastases combined with hyperthermic intraperitoneal chemotherapy (HIPEC) on synchronous colorectal cancer liver metastasis. MethodsA total of 144 patients with synchronous colorectal cancer liver metastasis who were admitted to our hospital between January 2018 and January 2019 were randomly assigned into a control group and an intervention group. The patients in the control group received simultaneous resection of liver metastases. The patients in the intervention group obtained simultaneous resection of liver metastases combined with HIPEC. The recent total effective rate of the 2 groups was compared, and the disease control rate of the 2 groups was calculated at 3 months after treatment. The patients were followed up for 3 years. The survival time of the 2 groups was observed and compared. Fasting venous blood was collected from patients in the 2 groups, and the carcinoembryonic antigen (CEA) level was compared. The level of quality of life scale (Short Form 36-item Health Survey) and the occurrence of adverse reactions were compared between the 2 groups. ResultsThe R0 complete resection rate in the intervention group was significantly higher than that in the control group (P < .05). The recent total effective rate in the intervention group (87.50%) was significantly higher than that in the control group (59.72%) (P < .05). The negative change of CEA in the intervention group was 72.22%, which was prominently higher than that in the control group of 43.06% (χ2 = 12.542, P < .001). After a 36-month follow-up, the overall survival rate of the observation group was significantly higher than that of the control group (hazard ratio, 2.54; 95% CI, 1.05–5.48; P < .001). The patients in the intervention group had significantly higher life quality scores of health status, social function, emotional function, physical function, and mental health than in the control group (P < .05). There was no significant difference in the incidence of complications between the 2 groups (P > .05). Age > 60 years, preoperative comorbidities, moderate and high differentiation of tumors, intraoperative blood loss > 150 mL, and less experienced surgeons were risk factors affecting the occurrence of complications after treatment and were closely correlated with the prognosis and survival of patients (P < .05). Patients with age ≤ 60 years, no preoperative comorbidities, low tumor differentiation, intraoperative blood loss ≤ 150 mL, more experienced surgeons, and complete R0 resection had a longer survival time. Age > 60 years, preoperative comorbidities, moderate and high differentiation of tumors, intraoperative blood loss > 150 mL, and less experienced surgeons were independent risk factors affecting the prognosis of patients with colorectal cancer liver metastases (P < .05), whereas R0 surgery was an independent protective factor for the prognosis (P < .05). ConclusionIn the treatment of synchronous colorectal cancer liver metastases, simultaneous resection of liver metastases in conjunction with HIPEC demonstrated superior efficacy. This approach may potentially extend patient survival and enhance quality of life and deserve to be extensively used in clinical practice.

Timing of surgery in patients with synchronous colorectal cancer liver metastases undergoing neoadjuvant chemotherapy: a propensity score analysis

BackgroundThe optimal timing of surgery after neoadjuvant chemotherapy (NAC) in patients with synchronous colorectal cancer liver metastases (SLM) remains controversial. We plan to analyze whether the choice of different surgical timings will have different effects on the perioperative and oncologic outcomes of patients.MethodWe retrospectively collected all patients who met the inclusion and exclusion criteria from 2010 to 2020 in West China Hospital. Patients were grouped according to time interval (TI) after NAC to surgery. The perioperative and oncologic outcomes of the two groups were compared after propensity score matching. Univariate and multivariate analyzes were used to screen factors associated with prognosis.ResultAmong 255 enrolled patients, 188 were matched with comparable baseline (94 each group). Patients in the 6≦TI≦8 group had longer operation time, less intraoperative blood loss, and less postoperative complications than those in the 4≦TI < 6 group. However, the overall survival (OS) (p = 0.012) and disease-free survival (DFS) (p = 0.013) of the patients in the 4≦TI < 6 group were better than those in the 6≦TI≦8 group. Subgroup analysis found that the above conclusions still apply in age ≥ 60, non-anemic patients, and patients who underwent R0 resection. OS was inversely correlated with TI in patients without preoperative jaundice. DFS was negatively correlated with TI in patients with preoperative jaundice. Multivariate analysis showed that the prolongation of TI after NAC to surgery was an independent prognostic risk factor for OS and DFS.ConclusionsPatients with SLM may be a better choice for surgery within 4–6 weeks after receiving NAC. Although patients with SLM undergoing surgery 4–6 weeks after NAC has a higher rate of postoperative complications, radical surgery is still recommended for a better survival benefit.

The neutrophil-to-lymphocyte ratio and lactate dehydrogenase combined in predicting liver metastasis and prognosis of colorectal cancer.

The neutrophil-to-lymphocyte ratio (NLR) and lactate dehydrogenase (LDH) level are inflammatory markers related to tumor growth and metabolism. This study investigated the value of preoperative NLR, LDH and the combination of NLR and LDH (NLR-LDH) for predicting colorectal cancer liver metastasis (CRLM) and tumor prognosis in the early stages of colorectal cancer (CRC). Three hundred patients undergoing CRC resection were included. Logistic regression analysis was used to estimate the correlation between CRLM time and inflammatory markers, and Kaplan-Meier survival and Cox regression analyses were used to estimate overall survival (OS). Forest plots were prepared based on the multivariate Cox analysis model and evaluated by receiver operating characteristic (ROC) curve analysis. The NLR cut-off value was 2.071 according to the ROC curve. The multivariate analysis showed that the elevated LDH level and a high NLR-LDH level were independent predictors of synchronous CRLM and OS (p < 0.05). The combination of a high NLR and elevated LDH and NLR-LDH levels suggested a poor prognosis and a significantly shorter median survival time than a low NLR and low levels of LDH and NLR-LDH. The ROC curve analysis results illustrated that the predictive value of the NLR-LDH score for synchronous CRLM [area under the curve (AUC) = 0.623, p < 0.001] and OS (AUC = 0.614, p = 0.001) was superior to that of the NLR or LDH score used alone. LDH and NLR-LDH are reliable, easy-to-use, independent biomarkers for predicting synchronous or metachronous CRLM and OS in CRC patients. The NLR is an important monitoring index for CRLM. Preoperative NLR, LDH and NLR-LDH may help to guide the use of therapeutic strategies and cancer surveillance.

Neoadjuvant chemotherapy versus upfront surgery as the initial treatment for patients with resectable, synchronous colorectal cancer liver metastases.

Although perioperative chemotherapy has been the standard treatment for colorectal cancer with resectable liver metastases (CRLM), studies that have compared neoadjuvant chemotherapy (NAC) and upfront surgery, especially in the setting of synchronous metastases are rare. We compared perioperative outcomes, overall survival (OS) and overall survival after recurrence (rOS) in a retrospective study of 281 total and 104 propensity score-matched (PSM) patients who underwent curative resection, with or without NAC, for synchronous CRLM, from 2006 to 2017. A Cox regression model was developed forOS. After PSM, 52 NAC and 52 upfront surgery patients with similar baseline characteristics were compared. Postoperative morbidity, mortality, and 5-year OS rate (NAC: 78.9%, surgery: 64.0%; p = 0.102) were similar between groups; however, the NAC group had better rOS (NAC: 67.3%, surgery: 31.5%; p = 0.049). Initial cancer stage (T4, N1-2), poorly differentiated histology, and >1 hepatic metastases were independent predictors of worse OS. Based on these factors, patients were divided into low-risk (≤1 risk factor, n = 115) and high-risk (≥2 risk factors, n = 166) groups. For high-risk patients, NAC yielded better OS than upfront surgery (NAC: 74.5%, surgery: 53.2%; p = 0.024). Although NAC and upfront surgery-treated patients had similar perioperative outcomes and OS, better postrecurrence survival was shown in patients with NAC. In addition, NAC may benefit patients with worse prognoses; therefore, physicians should consider patient disease risk before initiating treatment to identify patients who are most likely to benefit from chemotherapy.

Health-Related Quality of Life Following Simultaneous Resection for Synchronous Colorectal Cancer Liver Metastases.

Up to 25% of colorectal cancer patients present with synchronous liver metastases that can be treated with two operations or a single 'simultaneous' operation. Morbidity and mortality appear similar between approaches, however changes in health-related quality-of-life following simultaneous resection are not well reported. A prospective, feasibility trial for simultaneous resection of synchronous colorectal liver metastases was conducted. Patients completed the European Organization for Research and Treatment of Cancer QLQ-C30 and LMC21 at baseline (preoperatively), and 4 and 12weeks postoperatively. Week 4 and 12 scores were compared with baseline using t-tests. Minimally important clinical differences were considered as a 10-point difference from baseline. C30 and QLQ-LMC21 were completed at baseline, 4weeks, and 12weeks by 39 (95%), 35 (85%) and 34 (83%) patients, and 39 (95%), 33 (80%) and 33 (80%) patients, respectively; 79% and 75% had at least one MICD according to QLQ-C30 at 4 and 12 weeks. At 4 weeks, physical functioning (mean difference (MD) - 11.9%, p = 0.002), role functioning (MD - 23.6, p = 0.007), and pain (MD + 19.7, p = 0.017) had significant worsening from baseline. At 12 weeks postoperatively, role functioning (MD - 19.7, p = 0.011) and fatigue (MD + 14.3, p = 0.03) were the only domains that remained significantly worse. By 12 weeks, pain and physical functioning had returned to baseline. There were no major demographic differences among those with and without an MICD at 12 weeks. Simultaneous resection of colorectal liver metastases led to clinically significant worsening fatigue and role functioning that persisted at 12weeks post-surgery.

FDG metabolic parameter-based models for predicting recurrence after upfront surgery in synchronous colorectal cancer liver metastasis.

This study aimed to develop and validate post- and preoperative models for predicting recurrence after curative-intent surgery using an FDG PET-CT metabolic parameter to improve the prognosis of patients with synchronous colorectal cancer liver metastasis (SCLM). In this retrospective multicenter study, consecutive patients with resectable SCLM underwent upfront surgery between 2006 and 2015 (development cohort) and between 2006 and 2017 (validation cohort). In the development cohort, we developed and internally validated the post- and preoperative models using multivariable Cox regression with an FDG metabolic parameter (metastasis-to-primary-tumor uptake ratio [M/P ratio]) and clinicopathological variables as predictors. In the validation cohort, the models were externally validated for discrimination, calibration, and clinical usefulness. Model performance was compared with that of Fong's clinical risk score (FCRS). A total of 374 patients (59.1 ± 10.5 years, 254 men) belonged in the development cohort and 151 (60.3 ± 12.0 years, 94 men) in the validation cohort. The M/P ratio and nine clinicopathological predictors were included in the models. Both postoperative and preoperative models showed significantly higher discrimination than FCRS (p < .05) in the external validation (time-dependent AUC = 0.76 [95% CI 0.68-0.84] and 0.76 [0.68-0.84] vs. 0.65 [0.57-0.74], respectively). Calibration plots and decision curve analysis demonstrated that both models were well calibrated and clinically useful. The developed models are presented as a web-based calculator ( https://cpmodel.shinyapps.io/SCLM/ ) and nomograms. FDG metabolic parameter-based prognostic models are well-calibrated recurrence prediction models with good discriminative power. They can be used for accurate risk stratification in patients with SCLM. • In this multicenter study, we developed and validated prediction models for recurrence in patients with resectable synchronous colorectal cancer liver metastasis using a metabolic parameter from FDG PET-CT. • The developed models showed good predictive performance on external validation, significantly exceeding that of a pre-existing model. • The models may be utilized for accurate patient risk stratification, thereby aiding in therapeutic decision-making.

The Value of Laparoscopic Simultaneous Colorectal and Hepatic Resection for Synchronous Colorectal Cancer Liver Metastasis: A Propensity Score Matching Study.

PurposeThe aim of this study is to investigate the value of total laparoscopic simultaneous colorectal and hepatic resection in patients with synchronous colorectal cancer liver metastases (sCRLMs).MethodssCRLM patients who underwent simultaneous resection from December 2014 to December 2018 in Shanghai Cancer Center, Fudan University were recruited and analyzed retrospectively. The patients were divided into laparoscopic, open, and hybrid surgery groups. The intraoperative information, postoperative short-term outcome, and long-term survival were compared among the three groups. Propensity score matching (PSM) was performed to balance baselines.ResultsA total of 281 patients were recruited. After PSM, 34 patients were selected from both the laparoscopic and the open surgery group. Forty-seven patients were also selected from both the laparoscopic and the hybrid surgery group. The clinicopathologic baselines between the laparoscopic surgery group and the other two groups were well matched. All the operation-related indicators between laparoscopic surgery and hybrid surgery were similar. However, compared with open surgery, laparoscopic surgery showed significantly longer operation time (229.09 ± 10.94 min vs. 192.24 ± 9.49 min, p = 0.013) and less intraoperative blood loss [100.00 (50.00–300.00) ml vs. 200.00 (150.00–400.00) ml, p = 0.021]. For postoperative morbidity, there was no significant difference between the laparoscopic surgery group and the hybrid or the open surgery group (23.40% vs. 31.91% and 17.65% vs. 26.47%, p = 0.356 and p = 0.380). Long-term survival analysis showed that there were no significant differences in all 1-, 3-, and 5-year overall survival, liver recurrence-free survival (RFS), and whole RFS between laparoscopic surgery and hybrid surgery (p = 0.334, p = 0.286, and p = 0.558) or open surgery (p = 0.230, p = 0.348, and p = 0.450).ConclusionsLaparoscopic simultaneous resection for sCRLM shows slight advantages in surgical safety and short-term outcome, and does not compromise long-term survival.

Simultaneous or staged resection of synchronous colorectal cancer liver metastases: a 13-year institutional follow-up.

This study compared postoperative outcomes and survival rates of patients who underwent simultaneous or staged resection for synchronous colorectal cancer liver metastases. Between 2005 and 2018, 126 patients were registered prospectively at a university hospital in Sweden, 63 patients who underwent simultaneous resection were matched against 63 patients who underwent staged resection. The length of hospital stay was shorter for the simultaneous resection group, at 11 vs 16 days, p= <0.001. Fewer patients experienced recurrence in the simultaneous resection group 39 vs 50 patients, p=0.012. There were no significant differences in disease-free survival and overall survival between the groups. Age (hazard ratio [HR] 1.72; 95% CI 1.01-2.94; p=0.049) and Clavien-Dindo score (HR 2.22; 95% CI 1.06-4.67; p=0.035) had impact on survival. Colorectal cancer with synchronous liver metastases can be resected simultaneously, and enables a shorter treatment time without jeopardizing oncological outcomes.

HBV Infection Status Indicates Different Risks of Synchronous and Metachronous Liver Metastasis in Colorectal Cancer: A Retrospective Study of 3132 Patients with a 5-Year Follow-Up.

PurposePrevious studies on the effect of hepatitis B virus (HBV) infection on colorectal liver metastasis (CRLM) are contradictory. This study revealed different, more specific impacts of HBV on CRLM.Patients and MethodsA total of 3132 colorectal cancer patients treated from 2013 to 2015 were analyzed retrospectively and followed up for five years. The patients were divided into three groups: group A (chronic HBV infection, CHB); group B, (occult HBV infection, OHB) and group C (no HBV infection, NHB). The risk factors for CRLM, 5-year overall survival (OS), and liver disease-free survival (LDFS) were analyzed.ResultsA total of 905 patients (28.9%) had CRLM, with poor survival compared to those without CRLM (P < 0.01). The incidence of CRLM was 33.41% (138/413) in group A, 21.63% (138/638) in group B and 30.23% (629/2081) in group C (P < 0.05). Synchronous colorectal cancer liver metastasis (SYN-CRLM) was found in 425 patients (13.57%). CHB increased the risk of SYN-CRLM (P < 0.01), with a worse prognosis (P < 0.05). Metachronous colorectal cancer liver metastasis (MET-CRLM) was found in 480 patients (15.33%). OHB decreased the risk of MET-CRLM after surgery (P = 0.02), with a better 5-year LDFS (P = 0.01). Even without surgery, patients with OHB showed a lower incidence rate of MET-CRLM (P < 0.01).ConclusionThe incidence of CRLM in this study was approximately 28.9%. Surgery and different HBV infection statuses affected the occurrence of CRLM. Chronic HBV infection increased the risk of SYN-CRLM with poor prognosis. Occult HBV infection reduced the risk of MET-CRLM with better LDFS after surgery.

Minimally-invasive approach to synchronous colorectal cancer liver metastases: outcomes from a single centre

Minimally-invasive approach to synchronous colorectal cancer liver metastases: outcomes from a single centre

Simultaneous Resection for Synchronous Colorectal Cancer Liver Metastases: A Feasibility Clinical Trial

Introduction: Synchronous liver metastases from colorectal cancer may be resected simultaneously with the colorectal primary or as a separate staged operation, though data from randomized trials are limited. We tested the feasibility of a simultaneous resection clinical trial in order to obtain necessary information to plan a larger randomized trial. Methods: We conducted a multi-centre feasibility single arm trial that enrolled patients with synchronous colorectal cancer liver metastases eligible for simultaneous resection of the liver and primary tumour. Pre-specified criteria for feasibility were: proportion of eligible patients enrolled ≥66% and, proportion of enrolled patients who completed simultaneous resection ≥75%. Although not a component of the feasibility criteria, the pre-specified highest accepted proportion of 90-day major postoperative complications was 30%. Results: Of 61 eligible patients from February 2017 to August 2019, 41 were enrolled (67%, 95% confidence interval (CI), 55-78%) and 32 underwent simultaneous resection (78%, 95% CI, 63-88%). Four patients were not enrolled due to surgeon’s preference, 3 of which were due to complexity of resection (right hepatectomy and low anterior resection). Intraoperative complications during liver resection (n=4) and progression of disease (n=4) were the main reasons for not undergoing simultaneous resection. The 90-day incidence of Clavien-Dindo ≥ grade 3 complications was 41% (95% CI, 16-58%) and the 90-day postoperative mortality was 6% (95% CI, 1.7-20%). Conclusion: According to pre-specified criteria, enrolling patients with synchronous colorectal cancer liver metastases to a trial of simultaneous resection is feasible, however it is associated with higher than anticipated 90-day postoperative complications.

Simultaneous or 2-Staged Resections of Synchronous Colorectal Cancer Liver Metastases: A 13-Year Institutional Follow-up

Introduction: Simultaneous surgery for synchronous colorectal cancer liver metastases is controversial. Studies suggest that simultaneous surgery can reduce the number of complications, hospitalization and patient suffering. Some data suggests a shorter time to recurrence with this method. This study was performed to compare postoperative outcomes and survival rates in patients who underwent simultaneous or 2-staged resection.

Simultaneous resection for synchronous colorectal cancer liver metastases: A feasibility clinical trial.

We tested the feasibility of a simultaneous resection clinical trial in patients with synchronous colorectal cancer liver metastases to obtain the necessary information to plan a randomized trial. Multicenter feasibility single-arm trial enrolling patients with synchronous colorectal cancer liver metastases eligible for simultaneous resection. Prespecified criteria for feasibility were: proportion of eligible patients enrolled ≥66%, andthe proportion of enrolled patients who completed simultaneous resection ≥75%. The prespecified 90-day major postoperative complication rate was 30%. Of 61 eligible patients from February 2017 to August 2019, 41 were enrolled (67%; 95% confidence interval [CI], 55%-78%), 32 underwent simultaneous resection (78%; 95% CI, 63%-88%). Four patients were not enrolled due to the surgeon's preference, three were due to the complexity of resection (right hepatectomy and low anterior resection). Intraoperative complications during liver resection (n = 4) and progression of disease (n = 4) were the main reasons for not undergoing simultaneous resection. The 90-day incidence of major complications was 41% (95% CI, 16%-58%) and the 90-day postoperative mortality was 6% (95% CI, 1.7%-20%). According to prespecified criteria, enrolling patients with synchronous colorectal cancer liver metastases to a trial of simultaneous resection is feasible; however, it is associated with higher than anticipated 90-day postoperative complications.

The Italian Consensus on minimally invasive simultaneous resections for synchronous liver metastasis and primary colorectal cancer: A Delphi methodology.

At the time of diagnosis synchronous colorectal cancer, liver metastases (SCRLM) account for 15-25% of patients. If primary tumour and synchronous liver metastases are resectable, good results may be achieved performing surgical treatment incorporated into the chemotherapy regimen. So far, the possibility of simultaneous minimally invasive (MI) surgery for SCRLM has not been extensively investigated. The Italian surgical community has captured the need and undertaken the effort to establish a National Consensus on this topic. Four main areas of interest have been analysed: patients' selection, procedures, techniques, and implementations. To establish consensus, an adapted Delphi method was used through as many reiterative rounds were needed. Systematic literature reviews were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses instructions. The Consensus took place between February 2019 and July 2020. Twenty-six Italian centres participated. Eighteen clinically relevant items were identified. After a total of three Delphi rounds, 30-tree recommendations reached expert consensus establishing the herein presented guidelines. The Italian Consensus on MI surgery for SCRLM indicates possible pathways to optimise the treatment for these patients as consensus papers express a trend that is likely to become shortly a standard procedure for clinical pictures still on debate. As matter of fact, no RCT or relevant case series on simultaneous treatment of SCRLM are available in the literature to suggest guidelines. It remains to be investigated whether the MI technique for the simultaneous treatment of SCRLM maintain the already documented benefit of the two separate surgeries.

Risk scoring system for recurrence after simultaneous resection of colorectal cancer liver metastasis.

BackgroundThe simultaneous resection of synchronous colorectal cancer liver metastasis (SCRLM) has been widely applied. It is necessary to establish a risk scoring system to predict post-operative recurrence, especially in patients with neoadjuvant treatment.MethodsThe medical records of 221 patients undergoing simultaneous resection of CRLM were assessed in this study with a further 128 patients allocated to a validation group. All patients in the study group were classified according to their history of neoadjuvant treatment and univariate and multivariate analyses were applied to study independent risk factors. A score model was then generated according to the factors included. Our data set were also applied to validate three other existing scoring models [Fong clinical recurrence score (CRS), Konopke, and Zakaria disease-free survival (DFS) score], and the concordance index was calculated for comparison among these models.ResultsCRLM involving more than three nodes positive for a primary tumor was considered an independent risk factor for progression in patients without neoadjuvant treatment and all score models could discretely stratify patients according to disease free survival. In patients receiving neoadjuvant treatment, CRLM involving more than one node and transfusion invasion were major determinants in patients after treatment. However, only our scoring system and Fong’s CRS score could discretely discriminate patients. In the validation group, patients were significantly classified with the score system.ConclusionsExisting score models had better values for determining prognosis in patients with SCRLM, especially in those undertaking neoadjuvant treatment. Larger cohorts, along with more detailed clinical features and multicenter validation should be undertaken before utilization.

Nomograms predicting primary lymph node metastases and prognosis for synchronous colorectal liver metastasis with simultaneous resection of colorectal cancer and liver metastases.

It is necessary to identify valuable predictors of primary lymph node metastasis and prognosis for patients with synchronous colorectal cancer liver metastases (CRLM) with simultaneous resection of colorectal cancer (CRC) and liver metastases. This study constructed nomograms especially incorporating preoperative testing markers to predict primary lymph node metastases and prognosis in CRLM patients. By the highest Youden index (sensitivity + 1-specificity), the optimal cut-off values of testing markers for postoperative major complications and lymph node metastasis were identified. Multivariate regression analysis was used to reveal independent predictors for primary lymph node metastasis, postoperative major complications and progression-free survival (PFS). Nomograms based on independent predictors were constructed, and the discrimination and calibration were evaluated. A nomogram predicting primary lymph node metastasis was based on four risky independent predictors: American Society of Anesthesiologists (ASA) score 3-4, preoperative albumin (ALB) <41.15 g/L, poor differentiation and multiple liver metastases. The performance of the model was acceptable in predicting lymph node metastasis, with an area under the receiver operating characteristic curve (AUROC) of 0.655 (95% CI: 0.591-0.739). Calibration curves and the Hosmer-Lemeshow test revealed desirable model calibration (chi-square: 13.26, P=0.815). In the multivariate analysis, preoperative lactate dehydrogenase (LDH) ≥202.5 U/L [odds ratio (OR) =2.084, 95% confidence interval (CI): 1.039-4.181, P=0.039] and operation time ≥350.5 min (OR =2.848, 95% CI: 1.418-5.723, P=0.003) were independently associated with the presence of postoperative major complications. A nomogram predicting PFS was constructed based on poor differentiation, positive lymph node metastasis, bilobar liver distribution and R0 resection with good discrimination (C-index: 0.656±0.021) and calibration. This study established predictive nomograms specifically incorporating preoperative ALB and LDH levels for the prediction of primary lymph node metastasis and prognosis in synchronous CRLM patients with simultaneous resection, which have favourable discrimination and calibration to make individualized predictions.

Preoperative nomogram to predict survival following colorectal cancer liver metastasis simultaneous resection.

Simultaneous resection for patients with synchronous colorectal cancer liver metastases (CRLM) remains an optimal option for the sake of curability. However, few studies so far focus on outcome of this subgroup of patients (who receive simultaneous resection for CRLM). Substantial heterogeneity exists among such patients and more precise categorization is needed preoperatively to identify those who may benefit more from surgery. In this study, we formulated this internally validated scoring system as an option. Clinicopathological and follow-up data of 234 eligible CRLM patients undergoing simultaneous resection from January 2010 to March 2019 in our center were included for analysis. Patients were randomized to either a training or validation cohort. We performed multivariable Cox regression analysis to determine preoperative factors with prognostic significance using data in training cohort, and a nomogram scoring system was thus established. Time-dependent receiver operating characteristic (ROC) curve and calibration plot were adopted to evaluate the predictive power of our risk model. In the multivariable Cox regression analysis, five factors including presence of node-positive primary defined by enhanced CT/MR, preoperative CEA level, primary tumor location, tumor grade and number of liver metastases were identified as independent prognostic indicators of overall survival (OS) and adopted to formulate the nomogram. In the training cohort, calibration plot graphically showed good fitness between estimated and actual 1- and 3-year OS. Time-dependent ROC curve by Kaplan-Meier method showed that our nomogram model was superior to widely used Fong's score in prediction of 1- and 3-year OS (AUC 0.702 vs. 0.591 and 0.848 vs. 0.801 for 1- and 3-year prediction in validation cohort, respectively). Kaplan-Meier curves for patients stratified by the assessment of nomogram showed great discriminability (P<0.001). In this retrospective analysis we identified several preoperative factors affecting survival of synchronous CRLM patients undergoing simultaneous resection. We also constructed and validated a risk model which showed high accuracy in predicting 1- and 3-year survival after surgery. Our risk model is expected to serve as a predictive tool for CRLM patients receiving simultaneous resection and assist physicians to make treatment decision.

[Comparative study on prognosis of neoadjuvant chemotherapy followed by hepatic surgery versus upfront surgery in patients with synchronous colorectal liver metastasis].

Objective: To compare the survival outcome in patients with synchronous colorectal cancer liver metastasis receiving neoadjuvant chemotherapy followed by hepatic surgery versus upfront surgery strategies. Methods: A retrospective cohort study was carried out. Data of patients undergoing surgery at the Department of Hepatopancreatobiliary Surgery Unit I of Peking University Cancer Hospital from January 2008 to December 2018 for initially resectable synchronous colorectal liver metastasis were retrospectively collected. A total of 282 cases were enrolled, including 244 in the neoadjuvant chemotherapy group, 38 in the upfront surgery first group. The overall survival (OS) and progression-free survival (PFS) of the two groups were compared. A propensity score risk adjustment was used to eliminate potential bias between groups, and the covariates including sex, age, location of primary tumor, T stage, clinical risk score (CRS), RAS gene status, adjuvant chemotherapy, and resection margin status were included for adjustment. Results: In the neoadjuvant chemotherapy group, 244 cases received 4 (1-15) cycles of chemotherapy before hepatic resection, among whom 207 cases received oxaliplatin-based regimens, 37 cases received irinotecan-based regimens, and 90 cases received combined targeted agents in the first line treatment. The median follow-up time was 30 (5-134) months, and loss of follow-up was 1%. Before adjustment, Kaplan-Meier survival analysis showed that the 1-year and 3-year OS rates in the neoadjuvant chemotherapy group (95.1% and 66.4%) were better than those in the upfront surgery first group (94.7% and 51.5%, P=0.026); 1-year and 3-year PFS rates in neoadjuvant chemotherapy group (51.0% and 23.4%) were also better than those in surgery first group (39.5% and 11.5%, P=0.039). After propensity score risk adjustment, Cox multivariate analysis indicated that neoadjuvant chemotherapy was an independent protective factor of PFS (HR=0.664, 95% CI: 0.449-0.982, P=0.040), however, neoadjuvant chemotherapy was not an independent protective factor of OS (HR=0.651, 95% CI: 0.393-1.079, P=0.096). Subgroup analysis showed that the 1-year and 3-year OS rates in the patients with response to the first line treatment (194, including complete remission, partial remission and reduction but not partial remission) (96.9% and 67.1%) were better than those in the upfront surgery group (94.7% and 51.5%, P=0.026) after adjustment. However, the 1-year and 3-year OS rates in the patients without response to the first line treatment (50, including tumor progression or enlargement) were 90.0% and 63.3%, respectively, which were not significantly different with 94.7% and 51.5% in the upfront surgery group (P=0.310) after adjustment. Conclusions: For patients with resectable synchronous colorectal cancer liver metastasis, liver resection after neoadjuvant chemotherapy can provide longer PFS than upfront surgery. Although the whole OS benefit is not significant, patients with effective neoadjuvant first-line chemotherapy have better OS than those undergoing upfront surgery.

Synchronous resection of colorectal cancer primary and liver metastases: an outcomes analysis

BackgroundConcurrent resection of the primary cancer and synchronous colorectal cancer liver metastases (CRCLM) was evaluated for differences in outcomes following stratification of both the liver and colorectal resection. MethodsConsecutive cases of synchronous resection of both the CRC primary and CRCLM were reviewed retrospectively at a single, high-volume institution over a 17-year period (2000–2017). Results273 patients underwent simultaneous resection of CRCLM. The distribution of the primary lesion was similar between the colon (52.4%) and rectum (47.6%), while 46.9% of patients had bilobar liver disease. Major liver/major colorectal resection (n = 24) were significantly more likely to experience colorectal specific morbidity (OR 3.98, 95% CI 1.56–10.15, p = 0.004), liver specific morbidity (OR 7.4, 95% CI 2.22–24.71, p = 0.001), total morbidity (OR 2.91, 95% CI 1.18–7.18, p = 0.020) and 90-day mortality (OR 5.50, 95% CI 1.27–23.81, p = 0.023). Failure to receive adjuvant chemotherapy secondary to postoperative morbidity was associated with significantly worsened survival (HR for death 5.91, 95% CI 1.59–22.01, p = 0.008). ConclusionsPostoperative morbidity precluding the administration of adjuvant chemotherapy is associated with an increase in mortality. Combining a major liver with major colorectal resection is associated with a significant increase in major morbidity and 90-day mortality, and should be avoided.

Indication of Neoadjuvant Chemotherapy for Patients with Colorectal Cancer Liver Metastases in our Hospital

Background: Whether neoadjuvant chemotherapy (NAC) is approriate for the patients with initially resectable colorectal cancer liver metastases (CRLM) remains controversial. The indication of NAC was examined at the surgical meeting in our hospital. The aim of this study is to retrospectively validate our indication of NAC. Patients and Methods: From 2009 to 2019, 84 patients underwent hepatectomy for CRLM. They were divided into two groups: synchronous CRLM (SM-group n=56) and metachronous CRLM (MM-group n=28) and the indication of NAC was validated. Additionally, long-term outcomes were compared between patients who received NAC (NAC(+)-patients) and those didn´t receive NAC (NAC(-)-patients). Results: NAC was performed in 41 patients (73.3%) in SM-group and 12 patients (42.9%) in MM-group. In SM-group (28 single metastasis (sgl-Met) and 28 multiple metastases (multi-Met) ), the patients with multi-Met significantly received NAC (57.1% in sgl-Met vs. 89.3% in multi-Met, p=0.01). In MM-group (15 sgl-Met and 13 multi-Met), the period from excision of the primary cancer to the development of liver metastasis was tended to be shorter in NAC(+)-patients than NAC(-)-patients (NAC (+) 309 days vs. NAC (-) 656 days, median, p=0.09). In SM-group, there was no significant difference of 5-year OS between NAC(+)-patients and NAC(-)-patients(NAC (+) 63.6% vs. NAC (-) 74.6%, p=0.93). In MM-group, there was no significant difference between NAC(+)-patients and NAC(-)-patients(90.9% vs. 82.1%, p=0.40). Conclusion: NAC for CRLM tended to be performed to the patients with multiple- synchronous-metastasis and metachronous-metastases developing within 1year after excision of the primary cancer. According to our strategy, long-term outcomes were favorable.