Association of preoperative aspartate aminotransferase to platelet ratio index with outcomes and tumour microenvironment among colorectal cancer with liver metastases.

This study aims to investigate applicable robust biomarkers that can improve prognostic predictions for colorectal liver metastasis (CRLM) patients receiving simultaneous resection. A total of 1323 CRLM patients from multiple centres were included. The preoperative aspartate aminotransferase to platelet ratio index (APRI) level from blood of patients were obtained. Patients were stratified into a high APRI group and a low APRI group, and comparisons were conducted by analyzing progression-free survival (PFS), overall survival (OS) and postoperative early recurrence. Tumour samples of CRLM were collected to perform single-cell RNA sequencing and multiplex immunohistochemistry/immunofluorescence (mIHC/IF) to investigate the association of APRI levels and the tumour microenvironment of CRLM. Compared with APRI <0.33, PFS disadvantage (IPTW-adjusted HR = 1.240, P = 0.015) and OS disadvantage (IPTW- adjusted HR = 1.507, P = 0.002) of APRI ≥0.33 were preserved in the IPTW-adjusted Cox hazards regression analyses. An APRI ≥0.25 was associated with a significantly increased risk of postoperative early recurrence after adjustment (IPTW-adjusted OR = 1.486, P = 0.001). The external validation showed consistent results with the training cohort. In the high APRI group, the single-cell RNA sequencing results revealed a heightened malignancy of epithelial cells, the enrichment of inflammatory-like cancer-associated fibroblasts and SPP1+ macrophages associated with activation of malignant cells and fibrotic microenvironment, and a more suppressed-function T cells; mIHC/IF showed that PD1+ CD4+ T cells, FOXP3+ CD4+ T cells, PD1+ CD8+ T cells, FOXP3+ CD8+ T cells, SPP1+ macrophages and iCAFs were significantly increased in the intratumoral region and peritumoral region. This study contributed valuable evidence regarding preoperative APRI for predicting prognoses among CRLM patients receiving simultaneous resection and provided underlying clues supporting the association between APRI and clinical outcomes by single-cell sequencing bioinformatics analysis and mIHC/IF.

Nomogram predicting early recurrence defined by the minimum P value approach for colorectal liver metastasis patients receiving colorectal cancer resection with simultaneous liver metastasis resection: development and validation.

Background: Simultaneous resections have been increasingly performed for colorectal liver metastasis patients. However, studies explored risk stratification for these patients are scarce. Among which, a clear definition of early recurrence remains controversial and models for predicting early recurrence in these patients are lacking. Methods: Colorectal liver metastasis patients who developed recurrence followed by simultaneous resection were enrolled. Early recurrence was determined by the minimum P value method, and patients were divided into an early recurrence group and late recurrence group. Standard clinical data were collected from each patient including demographics features, preoperative laboratory tests and postoperative regular follow-up results. All the data were accessed by clinicians and recorded accordingly. The nomogram for early recurrence was constructed in the training cohort and validated externally in the test cohort. Results: The optimal value of early recurrence by the minimum P value method was 13 months. A total of 323 patients were included in the training cohort, of which 241 (74.6%) experienced early recurrence. Seventy-one patients were included in the test cohort, of which 49 (69.0%) experienced early recurrence. Significantly worse post-recurrence survival (median 27.0 vs. 52.8 months, P=0.00083) and overall survival (median 33.8 vs. 70.9 months, P<0.0001) were observed in patients with early recurrence in the training cohort. Positive lymph node metastases (P=0.003), tumour burden scores ≥4.09 (P=0.001), preoperative neutrophil-to-lymphocyte ratios ≥1.44 (P=0.006), preoperative blood urea nitrogen levels ≥3.55 µmol/L (P=0.017) and postoperative complications (P=0.042) were independently associated with early recurrence, and all these predictors were included in the nomogram. The nomogram for predicting early recurrence had a receiver operating characteristic curve of 0.720 in the training cohort and a receiver operating characteristic curve of 0.740 in the test cohort. The Hosmer-Lemeshow test and calibration curves showed acceptable model calibration in the training set (P=0.7612) and in the test set (P=0.8671). The decision curve analysis results for the training cohort and test cohort also indicated that the nomogram showed good clinical applicability. Conclusions: Our findings provide clinicians with new insights into accurate risk stratification for colorectal liver metastasis patients receiving simultaneous resection and contributing to the management of patients.

An elevated preoperative cholesterol-to-lymphocyte ratio predicts unfavourable outcomes in colorectal cancer liver metastasis patients receiving simultaneous resections: a retrospective study.

BACKGROUND: To explore the clinical prognostic utility of the preoperative cholesterol-to-lymphocyte ratio (CLR) in outcomes for colorectal cancer liver metastasis (CRLM) patients receiving simultaneous resection of the primary lesion and liver metastases. METHODS: A total of 444 CRLM patients receiving simultaneous resections were enrolled. The optimal cut-off value for CLR was determined using the highest Youden's index. Patients were divided into the CLR < 3.06 group and the CLR≥3.06 group. Propensity score matching analysis (PSM) and the inverse probability of treatment weighting (IPTW) method were conducted to eliminate bias between the two groups. The outcomes included short-term outcomes and long-term outcomes. Kaplan-Meier curves and log-rank tests were used to analyse progression-free survival (PFS) and overall survival (OS). RESULTS: In the short-term outcome analysis, after 1:1 PSM, 137 patients were distributed to the CLR < 3.06 group and CLR≥3.06 group. No significant difference was noted between the two groups (P > 0.1). Compared with patients with CLR < 3.06, patients with CLR≥3.06 had comparable operation times (320.0 [272.5-421.0] vs. 360.0 [292.5-434.5], P = 0.088), blood loss (200.0 [100.0-400.0] vs. 200.0 [150.0-450.0], P = 0.831), postoperative complication rates (50.4% vs. 46.7%, P = 0.546) and postoperative ICU rates (5.8% vs. 11.7%, P = 0.087). In the long-term outcome analysis, Kaplan-Meier analysis showed that compared with patients with CLR < 3.06, patients with CLR≥3.06 had worse PFS (P = 0.005, median: 10.2 months vs. 13.0 months) and OS (P = 0.002, median: 41.0 months vs. 70.9 months). IPTW-adjusted Kaplan-Meier analysis showed that the CLR≥3.06 group had worse PFS (P = 0.027) and OS (P = 0.010) than the CLR < 3.06 group. In the IPTW-adjusted Cox proportional hazards regression analysis, CLR≥3.06 was an independent factor for PFS (HR = 1.376, 95% CI 1.097-1.726, P = 0.006) and OS (HR = 1.723, 95% CI 1.218-2.439, P = 0.002). IPTW-adjusted Cox proportional hazards regression analysis including postoperative complications, operation time, intraoperative blood loss, intraoperative blood transfusion and postoperative chemotherapy revealed that CLR≥3.06 was an independent factor for PFS (HR = 1.617, 95% CI 1.252-2.090, P < 0.001) and OS (HR = 1.823, 95% CI 1.258-2.643, P = 0.002). CONCLUSIONS: The preoperative CLR level predicts unfavourable outcomes in CRLM patients receiving simultaneous resection of the primary lesion and liver metastases and should be taken into consideration when developing treatment and monitoring strategies.

Nomogram for tumour response based on prospective cohorts of hepatocellular carcinoma patients receiving immunotherapy combined with targeted therapy: development and validation.

Background: Although immunotherapy combined with targeted therapy can be effective for hepatocellular carcinoma (HCC), not all HCC patients respond to this treatment. Models for predicting tumour response in HCC patients receiving immunotherapy combined with targeted therapy are lacking. Methods: A total of 221 HCC patients from two independent prospective cohorts were retrospectively reviewed. The patients were randomly divided into training and validation cohorts at a ratio of 7:3. Standard clinical data were collected from each patient, including age, sex, hepatitis B infection status, laboratory tests, and immune target-related adverse events (itrAEs). Tumour responses were evaluated using the Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 guidelines. ItrAEs were assessed based on the Common Terminology Criteria for Adverse Events version 4.0. The nomogram for tumour response prediction was constructed based on the results of the multivariate logistic regression analysis, areas under the receiver operating characteristic curves (AUROCs) were used to determine the sensitivity and specificity of the model, and calibration plots and Hosmer-Lemeshow chi-square tests were performed to assess the calibration of the model. Results: In the multivariate logistic regression analysis, a solitary tumour (P=0.006), neutropenia (P=0.003) and hypertension (P=0.042) independently predicted objective response (OR). A nomogram for OR was established with AUROCs of 0.734, 0.675, 0.730, and 0.707 in the training, validation, first-line and second-line treatment sets, respectively. Tumour sizes less than 5 cm (P=0.005), a solitary tumour (P=0.037), prognostic nutritional indices greater than or equal to 54.3 (P=0.037), neutropenia (P=0.004) and fatigue (P=0.041) independently predicted disease control (DC). A nomogram for DC was established with AUROCs of 0.804, 0.667, and 0.768 in the training, first-line and second-line treatment sets, respectively. All the Hosmer-Lemeshow tests and calibration curves showed acceptable calibration. Conclusions: The current provides clinicians with new insights into selecting patients for immunotherapy combined with targeted therapy and contributes to the development of immunotherapy for HCC. It is necessary to expand the scale of our research and perform prospective studies to verify our findings.

Adverse Events of Immune Checkpoint Inhibitor-Based Therapies for Unresectable Hepatocellular Carcinoma in Prospective Clinical Trials: A Systematic Review and Meta-Analysis.

Background: The aim of the study was to investigate the incidence and spectrum of adverse events in unresectable hepatocellular carcinoma (HCC) patients treated with immune checkpoint inhibitors (ICIs) or ICI-based combinations. Summary: The study protocol was prospectively registered on PROSPERO (CRD42022319255). We searched PubMed, EMBASE, and the Cochrane Library for published clinical trials from database inception to April 22, 2022. Studies that included at least one group of unresectable HCC patients treated with ICIs or ICI-based combinations and reported the incidence or spectrum of treatment-related adverse events (trAEs) or immune-related adverse events (irAEs) were eligible. The incidence and spectra of all-grade and grade ≥3 trAEs were the primary outcomes. The profiles of irAEs, the incidence of trAEs leading to treatment discontinuation, and treatment-related mortalities were additional outcomes. We applied random-effects models to pool the incidence and spectra of adverse events. Subgroup analyses and meta-regression were performed. The literature search identified 2,464 records. Twenty studies (4,146 participants with HCC) met the eligibility criteria. The pooled incidences of all-grade trAEs, grade ≥3 trAEs, all-grade irAEs, and grade ≥3 irAEs were 80.1% (95% CI: 73.8-85.2), 35.4% (95% CI: 27.2-44.6), 31.1% (95% CI: 21.0-43.5), and 6.6% (95% CI: 3.6-11.8), respectively. ICIs plus oral targeted agents (all-grade OR = 17.07, 95% CI: 6.05-48.16, p < 0.001; grade ≥3 OR = 9.35, 95% CI: 4.53-19.29, p < 0.001) and ICIs plus intravenous targeted agents (all-grade OR = 4.91, 95% CI: 1.80-13.42, p = 0.003; grade ≥3 OR = 4.21, 95% CI: 1.42-12.48, p = 0.012) were associated with increased trAEs compared with monotherapy. The all-grade trAEs with the highest pooled incidences were reactive capillary endothelial proliferation (49.2%, 95% CI: 26.3-72.3), neutropenia (34.6%, 95% CI: 17.1-57.5), and proteinuria (32.8%, 95% CI: 19.8-49.2). The grade ≥3 trAEs with the highest pooled incidences were hypertension (11.1%, 95% CI: 4.0-29.0), neutropenia (10.5%, 95% CI: 7.0-15.4), and increased aspartate aminotransferase (7.7%, 95% CI: 6.3-9.4). The pooled incidence of trAEs leading to treatment discontinuation was 8.0% (95% CI: 6.0-10.5), and the overall incidence of treatment-related mortalities was 1.1%. Key Messages: This study comprehensively summarized the incidence and spectrum of trAEs in unresectable HCC patients receiving ICIs or ICI-based combinations in clinical trials. The results from this study will provide a useful reference to guide clinical practice.

Optimal surgical sequence for colorectal cancer liver metastases patients receiving colorectal cancer resection with simultaneous liver metastasis resection: A multicentre retrospective propensity score matching study.

BACKGROUND: There is little evidence regarding the optimal surgical sequence for colorectal cancer liver metastasis (CRLM) patients undergoing colorectal resection with simultaneous liver metastasis resection. METHODS: CRLM patients from five centers were retrospectively evaluated. The short-term outcomes included intraoperative and postoperative outcomes. Postoperative complications were measured according to the Clavien-Dindo classification. Grade I to II complications were defined as minor postoperative complications. The long-term outcomes were progression-free survival (PFS) and overall survival (OS). Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were performed to overcome the selection bias between colorectal resection first and liver resection first. RESULTS: A total of 1255 CRLM patients were included. In the multivariable logistic regression analysis, a body mass index (BMI) < 24 kg/m2, primary site in the left hemicolon, non-bilobar distribution of liver metastases and no preoperative chemotherapy were significantly associated with the likelihood of colorectal resection first. After 1:1 PSM, there was no significant difference between the colorectal resection first group and the liver resection first group. Compared with patients with colorectal resection first, patients with liver resection first had a comparable postoperative infection rate (15.0% vs. 16.0%, P = 0.735), a longer operation time (305.0 [231.3-416.0] vs. 300.0 [225.0-374.0], P = 0.033), more intraoperative blood loss (200.0 [150.0-400.0] vs. 100.0 [100.0-300.0], P < 0.001), a higher postoperative minor complication rate (28.7% vs. 20.7%, P = 0.023) and a higher postoperative ICU rate (14.7% vs. 8.7%, P = 0.022). IPTW-adjusted Kaplan-Meier analysis showed that patients who underwent colorectal resection first had a similar PFS (P = 0.702, median: 20.6 months vs. 16.6 months) and unfavourable OS (P = 0.014, median: 48.5 months vs. 67.0 months) compared with patients who underwent liver resection first. In the IPTW-adjusted Cox proportional hazards regression analysis, colorectal resection first was an unfavourable risk factor for OS (hazard ratio [HR] = 1.301, 95% CI 1.048-1.616, P = 0.017) and was not an independent predictor for PFS (HR = 0.986, 95% CI 0.831-1.170, P = 0.874). IPTW-adjusted Cox proportional hazards regression analysis, including postoperative complications, operation time, intraoperative blood loss and postoperative chemotherapy, produced consistent results. CONCLUSION: Although violating the "sterility principle", patients who underwent colorectal resection first did not have an increased postoperative infection rate and had some better short-term outcomes and comparable PFS than those who underwent liver resection first.

GRSF1 predicts an unfavorable prognosis and promotes tumorigenesis in lung adenocarcinoma based on bioinformatics analysis and in vitro validation.

Background: Effective biomarkers play a critical role in improving clinical approaches to treat lung adenocarcinoma (LUAD). However, many existing biomarkers have limitations due to a lot of factors, requiring the development of additional biomarkers to effectively predict the disease course and prognosis of LUAD. Guanine-rich RNA sequence binding factor 1 (GRSF1) participates in multiple biological processes, but its regulatory effect on LUAD remains unknown. The present study aimed to investigate the clinicopathological importance and biological role of GRSF1 in LUAD. Methods: The expression of GRSF1 was evaluated using multiple service portals. X-Tile software were used to determine the high and low GRSF1 groups and the relationships between GRSF1 expression and clinicopathological characteristics were then analyzed by R packages. Besides, prognostic significance was identified by the Gene Expression Profiling Interactive Analysis 2 (GEPIA2) and Kaplan-Meier (K-M) Plotter. Overall survival (OS) and disease-free survival (DFS) was the main outcome of prognosis analysis. The DNA copy number alterations (CNAs) and methylations were calculated using cBioPortal and R packages. The co-expressed genes of GRSF1 were obtained from LinkedOmics, and functional networks were then constructed by R clusterProfiler. Additionally, cell counting kit 8 (CCK-8) and colony formation assays were applied to verify the proliferation effects of GRSF1 on LUAD cells. Results: GRSF1 was significantly upregulated in the LUAD tissues compared to the non-tumor lung tissues (all P<0.05), and its expression was significantly correlated with gender (χ2=6.873, P=0.009) and T classification (χ2=13.62, P=0.003). Higher GRSF1 expression indicated worse OS [hazards ratio (HR) =1.6, P=0.0022] and DFS (HR =1.4, P=0.043), which suggested that GRSF1 was an independent prognostic factor for LUAD. DNA gain/amplification and hypomethylation may also contribute to GRSF1 upregulation. The functional annotation showed that GRSF1 regulates tumorigenesis through several signaling pathways. The knockdown of GRSF1 significantly suppressed lung cancer cell proliferation in vitro. Conclusions: The high expression of GRSF1 indicated an unfavorable prognosis and was closely related to LUAD tumor occurrence and development, which could be used as an effective prognostic biomarker for patients suffering from LUAD.

Outcomes of simultaneous resection for elderly patients with colorectal liver metastasis: A propensity score matching analysis.

BACKGROUND: Evidence on simultaneous resection for elderly patients (age ≥ 70 years) with colorectal liver metastasis (CRLM) is lacking. METHODS: Four hundred and eighty-two CRLM patients treated by simultaneous resection were categorised into young group (age < 70 years) and elderly group (age ≥ 70 years). Propensity score matching (PSM1) was performed to adjust for differences in baseline characteristics and compare short-term outcomes. An additional propensity score matching (PSM2) including short-term outcomes was performed to analyse survival. Subgroup analysis was performed in patients stratified by the Clinical Risk Score (CRS). RESULTS: After PSM1, 87 young group patients were matched to 50 elderly group patients. Patients in the elderly group had a significantly higher rate of overall post-operative complications (68.0% vs. 46.0%, p = 0.013). After PSM2, 89 young group patients were matched to 47 elderly group patients. Progression-free survival (PFS) was comparable between the two groups (median 11.0 months vs. 9.8 months, p = 0.346). Age ≥ 70 independently predicted worse overall survival (OS) (Hazard ratio, HR = 2.57, 95% confidence interval, CI 1.37-4.82) in multivariate analysis. In the subgroup multivariate analysis of patients with CRS score 3-5, age ≥ 70 was independently associated with worse PFS (HR = 1.62, 95% CI 1.01-2.62) and OS (HR = 2.34, 95% CI 1.26-4.35). CONCLUSIONS: Simultaneous resection for elderly CRLM patients is acceptable. Further studies are required to determine the optimal treatment for elderly CRLM patients with high CRS scores.

Nomogram for the prediction of lymph node metastasis and survival outcomes in rectal neuroendocrine tumour patients undergoing resection.

Background: The current study analysed rectal neuroendocrine tumour (RNET) patients undergoing resection to identify predictive factors and construct nomograms for lymph node metastasis, cancer-specific survival (CSS) and overall survival (OS). Methods: RNET patients registered in the Surveillance, Epidemiology, and End Results (SEER) database were included in this study. Multivariable logistic regression analysis was used to investigate the relationships between clinicopathological factors and lymph node metastasis. A multivariate competing risk model was applied to investigate factors independently associated with CSS. Through the Cox regression model, a multivariable analysis of OS was performed. Nomograms were established based on independent predictive factors. Calibration plots, receiver operating characteristic (ROC) curves and Brier scores were used to evaluate the predictive accuracy of the nomograms. Results: In this study, 1,253 RNET patients were included for further analysis. Tumour size ≥12 mm (P<0.001), T3/T4 stage (P<0.001) and M1 stage (P=0.001) were independently associated with lymph node metastasis. The performance of the nomogram was acceptable for predicting lymph node metastasis, with an area under the ROC curve (AUC) of 0.937 [95% confidence interval (CI): 0.874-1.000]. Calibration curves and the Hosmer-Lemeshow test revealed desirable model calibration (P=0.99996). The multivariate competing risk model analysis showed that grade II (P=0.017), tumour size ≥12 mm (P=0.007), AJCC TNM stage II (P=0.002), stage III (P<0.001) and stage IV (P<0.001) were significantly associated with worse CSS. In the competing risk nomogram model, the time-dependent AUC revealed good discriminatory ability of the model (time from 1 to 107 months, AUC >0.900), and the Brier score showed good accuracy of the nomogram, which was greater than that of the AJCC TNM stage. Multivariate Cox analysis showed that age >60 years (P=0.002), median income ≥$65,000 (P=0.013), AJCC TNM stage III (P=0.038) and AJCC TNM stage IV (P<0.001) were independently associated with worse OS. In the nomogram for the prediction of OS, the C-statistic was 0.703 (95% CI: 0.615-0.792), which was significantly better than that of the AJCC TNM stage (0.703 vs. 0.607, P=0.009). A calibration plot for the probability of survival demonstrated good calibration. Conclusions: The present study is the first to establish nomograms with great discrimination and accuracy for the prediction of lymph node metastases, CSS and OS in RNET patients, which can be used to guide treatment decision-making and surveillance.

Development and Validation of Prognostic Nomograms for Periampullary Neuroendocrine Neoplasms: A SEER Database Analysis.

(1) Background: Periampullary neuroendocrine neoplasms (NENs) are rare tumors that lack a prognostic prediction model. We aimed to design comprehensive and effective nomograms to predict prognosis; (2) Methods: Univariate and multivariate Cox analyses were used to screen out significant variables for the construction of the nomograms. The discrimination and calibration of the nomograms were carried out using calibration plots, concordance indices (C-indices), and area under time-dependent receiver operating characteristic curves (time-dependent AUCs). Decision curve analysis (DCA) was used to compare the clinical applicability of the nomograms, TNM (Tumor- Node-Metastasis) stage, and SEER stage; (3) Results: The independent risk factors for overall survival (OS) and cancer-specific survival (CSS) of patients with periampullary NENs included age, tumor size, histology, differentiation, N stage, M stage, and surgery, which were used to construct the nomograms. The calibration curves and C-indices showed a high degree of agreement between the predicted and actual observed survival rates. The AUCs displayed good calibration and acceptable discrimination of the nomograms. Additionally, the DCA curves indicated that the nomograms showed better clinical applicability; (4) Conclusions: We developed and validated nomogram prognostic models for patients with periampullary NENs. The nomograms provided insightful and applicable tools to evaluate prognosis.

Predictive value of red blood cell distribution width level on histological response and prognosis in colorectal liver metastases.

BACKGROUND: The red blood cell distribution width (RDW) level is a potential prognostic factor for solid tumours. We aimed to investigate the predictive value of pre-neoadjuvant chemotherapy (pre-NAC) RDW, preoperative RDW and the change in RDW on the pathological response and prognosis of patients with colorectal liver metastasis (CRLM), which was helpful for treatment decision-making, surveillance and prognostication. METHODS: This retrospective study analyzed clinicopathologic data, treatments and outcomes of 150 CRLM patients treated with NAC followed by liver resection at our hospital. The primary outcomes were progression-free survival (PFS) and overall survival (OS). The secondary outcome was postoperative major complications. The RDW level was presented as the RDW-SD level and the RDW-CV level. The optimal cut-off of RDW level was determined by X-tile analysis. The change in RDW was scored as 0 (decreased pre-NAC RDW and decreased preoperative RDW), 2 (elevated pre-NAC RDW and elevated preoperative RDW), or 1 (all other combinations). Multivariable logistic regression analysis was performed to determine the relationships between the tumour characteristics and pathological response and the postoperative major complications. A multivariate Cox proportional hazards model was used to evaluate the prognostic factors associated with survival. RESULTS: The optimal cut-off values of the RDW-CV and RDW-SD levels for survival were 13.5% and 42.2 fl, respectively. The multivariate analysis showed that a preoperative RDW-CV ≥13.5% (OR =3.215, 95% CI: 1.299-7.958, P=0.012) significantly predicted a favorable pathological response. The multivariate analysis revealed that a pre-NAC RDW-CV ≥13.5% (OR =2.462, 95% CI: 1.080-5.615, P=0.032) significantly predicted postoperative major complications. In the multivariate analysis, an RDW-CV change =2 (HR =0.487, 95% CI: 0.309-0.768, P=0.002) was a significant predictor of better PFS. The multivariate analysis also revealed that an RDW-SD change =2 (HR =0.532, 95% CI: 0.332-0.854, P=0.009) were an independent predictor of better OS. CONCLUSIONS: This study revealed that pre-NAC RDW, preoperative RDW and RDW changes may be reliable markers that could predict a pathological response and prognosis in CRLM patients receiving NAC followed by liver resection.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Impact of Postoperative Infectious Complications on Long-Term Outcomes for Patients Undergoing Simultaneous Resection for Colorectal Cancer Liver Metastases: A Propensity Score Matching Analysis.

OBJECTIVE: To investigate the impact of postoperative infectious complications (POI) on the long-term outcomes of patients with colorectal cancer liver metastasis (CRLM) after simultaneous resection of colorectal cancer and liver metastases. METHODS: Four hundred seventy-nine CRLM patients receiving simultaneous resection between February 2010 and February 2018 at our hospital were enrolled. A 1:3 propensity score matching analysis (PSM) analysis was performed to balance covariates and avoid selection bias. After PSM, 90 patients were distributed to the POI group, and 233 patients were distributed to the no POI group. A log-rank test was performed to compare the progression-free survival (PFS) and overall survival (OS) data. A multivariate Cox regression model was employed to identify prognostic factors influencing OS and PFS. A value of two-sided P<0.05 was considered statistically significant. RESULTS: Compared to patients in the no POI group, patients in the POI group were more likely to have hepatic portal occlusion (78.9% vs. 66.3%, P=0.021), operation time ≥325 min (61.1% vs. 48.1%, P=0.026), and intraoperative blood loss ≥200 ml (81.1% vs. 67.6%, P=0.012). In multivariate analysis, intraoperative blood loss ≥200 ml (OR = 2.057, 95% CI: 1.165-3.634, P=0.013) was identified as the only independent risk factor for POI. Patients with POI had a worse PFS (P<0.001, median PFS: 7.5 vs. 12.7 months) and a worse OS (P=0.010, median OS: 38.8 vs. 59.0 months) than those without POI. After 1:3 PSM analysis, no differences in clinicopathologic parameters were detected between the POI group and the no POI group. Patients with POI had a worse PFS (P=0.013, median PFS: 7.5 vs. 11.1 months) and a worse OS (P=0.020, median OS: 38.8 vs. 59.0 months) than those without POI. Multivariate analysis showed that POI was an independent predictor for worse PFS (HR=1.410, 95% CI: 1.065-1.869, P=0.017) and worse OS (HR=1.682, 95% CI: 1.113-2.544, P=0.014). CONCLUSIONS: POI can significantly worsen the long-term outcomes of CRLM patients receiving simultaneous resection of colorectal cancer and liver metastases and should be considered to improve postoperative management and make better treatment decisions for these patients.