Recurrence Prediction by Circulating Tumor DNA in the Patient with Colorectal Liver Metastases After Hepatectomy: A Prospective Biomarker Study.

BACKGROUND: The recurrence rate after hepatic resection of colorectal liver metastases (CRLM) remains high. This study aimed to investigate postoperative circulating tumor DNA (ctDNA) based on ultra-deep next-generation sequencing (NGS) to predict patient recurrence and survival. METHODS: Using the high-throughput NGS method tagged with a dual-indexed unique molecular identifier, named the CRLM-specific 25-gene panel (J25), this study sequenced ctDNA in peripheral blood samples collected from 134 CRLM patients who underwent hepatectomy after postoperative day 6. RESULTS: Of 134 samples, 42 (31.3%) were shown to be ctDNA-positive, and 37 resulted in recurrence. Kaplan-Meier survival analysis showed that disease-free survival (DFS) in the ctDNA-positive subgroup was significantly shorter than in the ctDNA-negative subgroup (hazard ratio [HR], 2.96; 95% confidence interval [CI], 1.91-4.6; p < 0.05). When the 42 ctDNA-positive samples were further divided by the median of the mean allele frequency (AF, 0.1034%), the subgroup with higher AFs showed a significantly shorter DFS than the subgroup with lower AFs (HR, 1.98; 95% CI, 1.02-3.85; p < 0.05). The ctDNA-positive patients who received adjuvant chemotherapy longer than 2 months showed a significantly longer DFS than those who received treatment for 2 months or less (HR, 0.377; 95% CI, 0.189-0.751; p < 0.05). Uni- and multivariable Cox regression indicated two factors independently correlated with prognosis: ctDNA positivity and no preoperative chemotherapy. CONCLUSION: The study demonstrated that ctDNA status 6 days postoperatively could sensitively and accurately predict recurrence for patients with CRLM using the J25 panel.

Prognostic value of the combination of primary tumor location and RAS mutational status on patients with colorectal liver metastasis undergoing hepatectomy.

OBJECTIVE: To assess prognostic influences of RAS mutational status and primary tumor site on cases with colorectal liver metastasis (CRLM) who underwent hepatectomy. METHODS: Clinicopathological data of 762 patients with CRLM who underwent hepatectomy between January 2000 and November 2018 were retrospectively analyzed. The left-sided tumors (LST) included tumors located in the splenic flexure, descending colon, sigmoid colon, and rectum; while right-sided tumors (RST) included those located in the cecum, ascending colon, and transverse colon. RAS mutational status was determined using Sanger sequencing or next-generation sequencing, including KRAS (Codons 12, 13, and 61) and NRAS (Codons 12, 13, and 61), which were defined as wild-type (RASwt) and mutant-type (RASmut), respectively. Survival curves were plotted using the Kaplan-Meier plotter and compared by the log rank test. The clinicopathological data were analyzed using univariate and multivariate analyses. RESULTS: The 5-year overall survival (OS) in the LST group was longer than that in the RST group (OS: 47.1% vs. 31.0%, p = 0.000, respectively), and the OS in the RASwt group was longer compared with that in the RASmut group (OS: 53.6% vs. 24.0%, p = 0.000). Besides, overall survival of the patients after hepatectomy was alternative, which was stratified by primary tumor site, with the 1-, 3-, and 5-year survival rates of 93.1%, 62.1%, and 47.1% for patients with LST, and 91.1%, 42.8%, and 31.0% for patients with RST, respectively. OS and disease-free survival (DFS) were significantly different stratified by RAS mutational status, with the 1-, 3-, and 5-year rates of 96.9%, 67.9%, and 53.6% for patients with RASwt tumors, and 85.7%, 41.5%, and 24.0% for patients with RASmut tumors, respectively. The 1-, 3-, and 5-year DFS rates were 51.9%, 30.0%, and 26.7% for patients with RASwt tumors, and 35.8%, 18.2%, and 14.9% for patients with RASmut tumors, respectively. The results of multivariate analysis showed that RAS mutational status and primary tumor site were both independent influencing factors of OS. CONCLUSION: RAS mutational status and primary tumor site affect OS independently in CRLM patients undergoing hepatectomy. The worse prognosis of RST cannot be simply attributed to the imbalance of RAS mutational status in different primary tumor sites.

Perioperative second-line chemotherapy is beneficial for resectable liver metastases that occur during or early after adjuvant chemotherapy for colorectal cancer.

BACKGROUND: The prognosis of patients with liver metastases during or early after adjuvant chemotherapy for colorectal cancer (CRC) is significantly worse. This study aimed to explore the efficacy of perioperative second-line chemotherapy in prolonging survival in those patients. METHODS: Patients who underwent liver resection, with resectable liver metastases that occurred within 12 months after the last cycle of adjuvant chemotherapy for CRC, from January 2006 to December 2019, were included. The long-term outcome of overall survival (OS) and progression-free survival (PFS) between different groups was analyzed. RESULTS: A total of 200 patients were included, of whom 112 underwent direct hepatectomy and 88 received upfront second-line chemotherapy. OS and PFS were significantly better in patients receiving upfront second-line chemotherapy than direct surgery (PFS, P = 0.016; OS, P = 0.013). Further analysis showed that perioperative second-line chemotherapy could provide a greater survival benefit, which was also confirmed by propensity score matching (OS: P = 0.03; PFS: P = 0.04). Multivariate analysis determined that perioperative second-line chemotherapy was an independent factor influencing OS (OR [95% CI]: 0.468 [0.294-0.744], P = 0.001) and PFS (OR [95% CI]: 0.517 [0.353-0.758], P = 0.001). DISCUSSION: Perioperative second-line chemotherapy could improve the survival of patients who underwent hepatectomy, with resectable liver metastases that occurred during or early after adjuvant chemotherapy for CRC.

Characterization of genomic alterations in Chinese colorectal cancer patients with liver metastases.

BACKGROUND: The exploration of genomic alterations in Chinese colorectal liver metastasis (CRLM) is limited, and corresponding genetic biomarkers for patient's perioperative management are still lacking. This study aims to understand genome diversification and complexity that developed in CRLM. METHODS: A custom-designed IDT capture panel including 620 genes was performed in the Chinese CRLM cohort, which included 396 tumor samples from metastatic liver lesions together with 133 available paired primary tumors. RESULTS: In this Chinese CRLM cohort, the top-ranked recurrent mutated genes were TP53 (324/396, 82%), APC (302/396, 76%), KRAS (166/396, 42%), SMAD4 (54/396, 14%), FLG (52/396, 13%) and FBXW7 (43/396, 11%). A comparison of CRLM samples derived from left- and right-sided primary lesions confirmed that the difference in survival for patients with different primary tumor sites could be driven by variations in the transforming growth factor ß (TGF-ß), phosphatidylinositol 3-kinase (PI3K) and RAS signaling pathways. Certain genes had a higher variant rate in samples with metachronous CRLM than in samples with simultaneous metastasis. Overall, the metastasis and primary tumor samples displayed highly consistent genomic alterations, but there were some differences between individually paired metastases and primary tumors, which were mainly caused by copy number variations. CONCLUSION: We provide a comprehensive depiction of the genomic alterations in Chinese patients with CRLM, providing a fundamental basis for further personalized therapy applications.

The prognostic impact of resection margin status varies according to the genetic and morphological evaluation (GAME) score for colorectal liver metastasis.

BACKGROUND: Surgical margin status remains a controversial factor in predicting the outcome of colorectal liver metastases (CRLM) resection. Our study aims to evaluate the effects of surgical margins on oncologic outcomes with regard to the genetic and morphological evaluation (GAME) score. METHODS: R1 resection was defined as having a less than 1 mm margin width. Patients who underwent surgery for CRLM from January 2005 to December 2018 were recruited. The patients were divided into two risk subgroups, namely, the low or medium risk (GAME 0-3) and high-risk (GAME score 4 or more) groups. The effects of margin status on overall survival (OS) and recurrence-free survival rate (RFS) were examined. RESULTS: In total, 661 patients were recruited, among which 159 (24.1%) had R1 resection. Before hepatectomy, 514 patients showed a low or medium risk (R1 resection: n = 124), while 147 patients demonstrated a high risk (R1 resection: n = 35). In the whole cohort, multivariable analysis did show that R1 resection was associated with worse RFS and OS. While further research only found that in the low or medium risk group, R1 resection was related to poor OS and RFS. Meanwhile, in the high risk group, no significant difference was found in the median OS and RFS among patients with R0 or R1 resection. CONCLUSION: The prognostic role of margin status varied according to the GAME score. Margin clearance only improved survival rates in patients with low or medium GAME score. In contrast, R1 resection demonstrated similar oncologic outcomes with R0 resection in patients with high GAME score.

En bloc right hemicolectomy with pancreatoduodenectomy for right-sided colon cancer invading duodenum.

BACKGROUND: En bloc right hemicolectomy with pancreatoduodenectomy (RHCPD) is the optimum treatment to achieve the adequate margin of resection (R0) for locally advanced right-sided colon cancer with duodenal invasion. Information regarding the indications and outcomes of this procedure is limited. METHOD: In this retrospective study, 2269 patients with right colon cancer underwent radical right colectomy between October 2010 and May 2019, in which 19 patients underwent RHCPD for LARCC were identified. The overall survival (OS), disease-free survival (DFS), operative mortality, postsurgical complications, gene mutational analysis, and prognostic factors were evaluated. Survival was estimated using Kaplan-Meir method. RESULTS: Of these 19 patients who underwent LARCC, the OS was 88%, 66%, and 58% at 1, 3, and 5 years. The DFS was 72%, 56%, and 56% at 1, 3, and 5 years. The median operative time was 320 min (range: 222-410 min), and the median operative blood loss was 268 mL (range: 100-600 mL). The OS was significantly better among patients with well-differentiated tumor, N0 stage, and high microsatellite instability (MSI) and in patients who received adjuvant chemotherapy. The major postoperative complications occurred in 8 patients (42%), with pancreatic fistula (PF) being the most common. On the basis of the univariate analysis, poorly differentiated tumor, regional lymph node dissemination, MSI status, and no perioperative chemotherapy were the significant predictors of poor survival (P < 0.05). CONCLUSIONS: This study suggests that RHCPD is feasible and can achieve complete tumor clearance with favorable outcome, particularly in patients with lymph node-negative status.

Liver resection for colorectal liver-limited metastases in elderly patients: a propensity score matching analysis.

BACKGROUND: Few studies have focused on the role of hepatectomy for colorectal liver-limited metastases in elderly patients compared to matched younger patients. METHODS: From January 2000 to December 2018, 724 patients underwent hepatectomy for colorectal liver-limited metastases. Based on a 1:2 propensity score matching (PSM) model, 64 elderly patients (≥ 70 years of age) were matched to 128 younger patients (< 70 years of age) to obtain two balanced groups with regard to demographic, therapeutic, and prognostic factors. RESULTS: There were 73 elderly and 651 younger patients in the unmatched cohort. Compared with the younger group (YG), the elderly group (EG) had significantly higher proportion of American Society of Anesthesiologists score III and comorbidities and lower proportion of more than 3 liver metastases and postoperative chemotherapy (p < 0.05). After PSM for these factors, rat sarcoma virus proto-oncogene/B-Raf proto-oncogene (RAS/BRAF) mutation status and primary tumor sidedness, the EG had significantly less median intraoperative blood loss than the YG (175 ml vs. 200 ml, p = 0.046), a shorter median postoperative hospital stay (8 days vs. 11 days, p = 0.020), and a higher readmission rate (4.7% vs.0%, p = 0.036). The EG also had longer disease-free survival (DFS), overall survival (OS), and cancer-specific survival (CSS) compared to the YG, but these findings were not statistically significant (p > 0.05). Old age was not an independent factor for DFS, OS, and CSS by Cox multivariate regression analysis (p > 0.05). CONCLUSIONS: Hepatectomy is safe for colorectal liver-limited metastases in elderly patients, and these patients may subsequently benefit from prolonged DFS, OS, and CSS.

Comparison of sequential, delayed and simultaneous resection strategies for synchronous colorectal liver metastases.

BACKGROUND: The present study aimed to compare the perioperative safety and long-term survival of patients with synchronous colorectal liver metastases undergoing sequential resection (SeR), delayed resection (DeR) and simultaneous resection (SiR). METHODS: From January 2007 to December 2016, data from patients undergoing surgery at Peking University Cancer Hospital for synchronous colorectal liver metastases were retrospectively collected. The above three different surgical strategies were compared. RESULTS: A total of 233 cases were included, with 49 in the SeR group, 98 in the DeR group and 86 in the SiR group. The incidence of severe complications was 26.7% in the SiR group, higher than that in the DeR group (11.2%, P = 0.007) and the SeR group (16.3%, P = 0.166). The overall survival at 1 and 3 years in the SeR group (93.9 and 50.1%) was lower than that in the DeR group (94.9 and 64.8%, P = 0.019), but not significantly different from that in the SiR group (93.0 and 55.2%, P = 0.378). Recurrence-free survival at 1 and 3 years in the SeR group (22.4 and 18.4%) was lower than that in the DeR group (43.9 and 24.2%, P = 0.033) but not significantly different from that in the SiR group (31.4 and 19.6%, P = 0.275). Cox multivariate analysis indicated that T4, lymph node-positive primary tumour, liver metastases > 30 mm and SiR (compared with DeR) were correlated with poor prognosis. CONCLUSION: Simultaneous resection has a relatively higher incidence of severe complications, and with a staged resection strategy, the prognosis of delayed resection was better than that of sequential resection.

The individualized selection of Pancreaticoenteric anastomosis in Pancreaticoduodenectomy.

BACKGROUND: The mortality following pancreaticoduodenectomy has markedly decreased but remains an important challenge for the complexity of operation and technical skills involved. The present study aimed to clarify the impact of individualized pancreaticoenteric anastomosis and management to postoperative pancreatic fistula. METHODS: Data from 529 consecutive pancreaticoduodenectomies were retrospectively analysed from the Hepatobiliary and Pancreatic Surgery Unit I, Peking Cancer Hospital. The pancreaticoenteric anastomosis was determined based on the pancreatic texture and diameter of the main pancreatic duct. The amylase value of the drainage fluid was dynamically monitored postoperatively on days 3, 5 and 7. A low speed intermittent irrigation was performed in selected patients. Intraoperative and postoperative results were collected and compared between the pancreaticogastrostomy (PG) group and pancreaticojejunostomy (PJ) group. RESULTS: From 2010 to 2019, 529 consecutive patients underwent pancreaticoduodenectomy. Pancreaticogastrostomy was performed in 364 patients; pancreaticojejunostomy was performed in 150 patients respectively. The clinically relevant pancreatic fistula (CR-POPF) was 9.8% and mortality was zero. The soft pancreas, diameter of main pancreatic duct≤3 mm, BMI ≥ 25, operation time > 330 min and pancreaticogastrostomy was correlated with postoperative pancreatic fistula significantly. The CR-POPF of PJ was significantly higher than that of PG in soft pancreas patients; the operation time of PJ was shorter than that of PG significantly in hard pancreas patients. Intraoperative blood loss and operation time of PG was less than that of PJ significantly in normal pancreatic duct patients (p < 0.05). CONCLUSIONS: Individualized pancreaticoenteric anastomosis should be determined based on the pancreatic texture and pancreatic duct diameter. The appropriate anastomosis and postoperative management could prevent mortality.

Comparing Baseline VAF in Circulating tumor DNA and Tumor Tissues Predicting Prognosis of Patients with Colorectal Cancer Liver Metastases After Curative Resection.

INTRODUCTION: The prognostic value of baseline variant allele frequency (VAF) in circulating tumor DNA (ctDNA) of colorectal cancer liver metastases (CRLM) patients after curative resection was rarely investigated. METHODS: A single-center prospective study was performed to investigate the prognostic impact of baseline VAF in ctDNA and matched tumor tissues of CRLM patients after curative resection between May 2019 and May 2021 by the Illumina NovoSeq 6000 platform. The relationship of the tumor burden score (TBS) and the VAF in ctDNA and matched tumor tissues was evaluated by the Pearson correlation method. The survival curves of recurrence-free survival (RFS) and overall survival (OS) were plotted. Factors associated with RFS were calculated using Cox regression analysis, and an integrated prognostic model using significant baseline variables was proposed. RESULTS: There were 121 patients with baseline ctDNA and matched tumor tissues enrolled in the study. A total of 417 mutations spanning 20 genes were identified in baseline tumor tissues of 119/121 (98.3%) cases. The overall mutations in tumor tissues were completely covered by ctDNA in 52 of 121(43.0%) patients. Baseline VAF in ctDNA but not in tumor tissues was significantly correlated to TBS of CRLM (R=0.36, p<0.001). Significantly longer RFS but not OS was observed in patients with lower VAF in ctDNA compared to those with higher one (p<0.001 and p=0.33 respectively). Multivariate Cox regression analysis showed higher VAF in baseline ctDNA was an independent risk factor for RFS. An integrated prognostic model including baseline metastasis location and VAF in ctDNA outperformed the traditional CRS model in predicting RFS. CONCLUSION: Baseline VAF in ctDNA but not in tumor tissues influenced RFS of CRLM patients after curative resection.

Low expression of PAI-2 as a novel marker of portal vein tumor thrombosis and poor prognosis in hepatocellular carcinoma.

BACKGROUND: Plasminogen activator inhibitor (PAI)-2 was previously shown to be less frequently expressed in hepatocellular carcinoma (HCC). The present study was designed to investigate the clinical, pathological, and prognostic significance of PAI-2 expression in HCC. METHODS: Expression of PAI-2 was detected immunohistochemically for specimens from 78 patients with HCC after hepatic resection and correlated with clinicopathological features and patient survival. Risk factors of portal vein tumor thrombosis (PVTT) were also analyzed. RESULTS: Positive PAI-2 staining was observed in tumor and non-tumor tissues from 21 (26.9%) and 56 (71.8%) patients, respectively. Plasminogen activator inhibitor-2 negativity in tumor tissues was significantly associated with PVTT, with a high sensitivity not only in univariate analysis but also in multivariate analysis. In addition, positive PAI-2 staining was related to smaller tumor size and prolonged patient survival. The Cox regression model identified intratumoral PAI-2 staining as an independent prognosticator in patients with HCC after resection. CONCLUSIONS: Our data demonstrated that low expression of PAI-2 serves as a novel marker of PVTT and poor prognosis in HCC.

Expression of plasminogen activator inhibitor-2 is negatively associated with invasive potential in hepatocellular carcinoma cells.

OBJECTIVE: To investigate the association between plasminogen activator inhibitor (PAI)-2 expression and invasive potential in hepatocellular carcinoma (HCC) cells. METHODS: The HCC cell lines with high, low, and non-metastatic potentials, namely MHCC97-H, MHCC97-L, and SMMC-7721 respectively, were cultured in vitro. Matrigel invasion assay and Western blot of PAI-2 protein expression were conducted. RESULTS: The number of invaded cells in MHCC97-L was significantly higher than that in SMMC-7721 (P=0.005), whereas that in MHCC97-H was higher than in MHCC97-L (P=0.017) and SMMC-7721 (P=0.001). Contrarily, PAI-2 protein expression was gradually reducing from SMMC-7721, MHCC97-L, to MHCC97-H (MHCC97-H vs. MHCC97-L, P<0.001; MHCC97-H vs. SMMC-7721, P=0.001; MHCC97-L vs. SMMC-7721, P=0.001). The Pearson's correlation analysis revealed a significant negative association between invaded cell number and PAI-2 expression (r=-0.892, P=0.001). CONCLUSION: PAI-2 expression may be negatively associated with the invasive potential of HCC.

[Surgical outcomes of second liver resections for recurrent hepatic metastases from colorectal cancer].

OBJECTIVE: To compare the clinical efficacies and safety of primary versus second liver resection for recurrent colorectal metastases to liver. METHODS: Between January 2000 and March 2011, a total of 126 patients underwent liver resections for metastases from colorectal cancer at our institution. Among these, 16 patients underwent repeat liver resections. The comparisons were made for primary and second liver resections in blood loss volume, complications, hospital stay, operative duration and 1, 3, 5- year survival rates. RESULTS: Compared with primary liver resection group, the 1, 3, 5-year survival rates of second liver resection group were 93.8%, 56.1% and 37.4% respectively. For second hepatectomy group, blood loss volume was (323.8 ± 230.9) ml, operative duration (216.9 ± 79.7) min, postoperative hospital stay (23.4 ± 13.9) days and complication rate 18.8%. Compared with primary hepatectomy, there was no difference between two groups. CONCLUSION: Second liver resection may provide long-term survival rates similar to those of primary liver resections. Repeat liver resection is warranted when potentially curative.

Five-year survival post hepatectomy for colorectal liver metastases in a real-world Chinese cohort: Recurrence patterns and prediction for potential cure.

BACKGROUND: Patients with a 5-year recurrence-free survival post liver resection for colorectal cancer liver metastases (CRLM) are considered to be potentially cured. However, there is a deficit of data on long-term follow-up and the recurrence status among these patients in the Chinese population. We analyzed real-world follow-up data of patients with CRLM who underwent hepatectomy, explored the recurrence patterns, and established a prediction model for a potential cure scenario. METHODS: Patients who underwent radical hepatic resection for CRLM during 2000-2016, with actual follow-up data for at least 5 years, were enrolled. The observed survival rate was calculated and compared among the groups with different recurrence patterns. The predictive factors for 5-year non-recurrence were determined using logistic regression analysis; a recurrence-free survival model was developed to predict long-term survival. RESULTS: A total of 433 patients were included, of whom 113 patients were found non-recurrence after 5 years follow-up, with a potential cure rate of 26.1%. Patients with late recurrence (>5 months) and lung relapse showed significantly superior survival. Repeated localized treatment significantly improved the long-term survival of patients with intrahepatic or extrahepatic recurrences. Multivariate analysis showed that RAS wild-type CRC, preoperative CEA <10 ng/ml, and liver metastases ≤3 were independent factors for a 5-year disease-free recurrence. A cure model was developed based on the above factors, achieving good performance in predicting long-term survival. CONCLUSIONS: About one quarter patients with CRLM could achieve potential cure with non-recurrence at 5-year after surgery. The recurrence-free cure model could well distinguish the long-term survival, which would aid clinicians in determining the treatment strategy.

Postoperative complications predict poor outcomes only in patients with a low modified clinical score after resection of colorectal liver metastases: a retrospective cohort study.

The aim was to identify the optimal criteria of postoperative complications (POCs) for predicting oncological outcomes after hepatectomy for colorectal liver metastases (CRLMs) and to investigate the variable prognostic implications of POCs according to the modified clinical score (M-CS). We identified 751 patients who underwent curative hepatic resection for CRLM between 2007 and 2018. Patients were categorized based on the M-CS. The impact of the severity [≥ Clavien-Dindo grade (C-D) III or comprehensive complication index (CCI) ≥ 26.2] or type [any infectious complications of POC (Inf-poc)] of POC on overall survival (OS) and recurrence-free survival (RFS) was assessed by univariate and multivariable analyses in different groups. Patients with a major or infectious complication were not associated with either RFS or OS in multivariable analysis of the whole cohort. However, patients with a high CCI had a worse OS (HR 1.51, P = 0.004). Among patients with low M-CS, patients with high CCI had worse OS (HR 1.49, P = 0.035) and RFS (HR 1.32, P = 0.048) than those without high CCI. In contrast, the survival disadvantage of a high CCI was not present in patients with a high M-CS. Compared to Inf-poc or major complications, a high CCI decreased long-term OS in patients treated with hepatectomy for CRLM. High CCI has a variable prognostic impact after hepatic resection for CRLM depending on the M-CS. POC is not a decisive factor to justify the use of hepatectomy for CRLM in patients with high M-CS.

Impact of Age of Onset on Survival after Hepatectomy for Patients with Colorectal Cancer Liver Metastasis: A Real-World Single-Center Experience.

PURPOSE: The incidence of early-onset CRC is increasing. However, the effect of age of onset on the long-term outcome of colorectal cancer liver metastasis (CRLM) remains unclear. This study aimed to evaluate the association between the age of onset and the oncological outcome of CRLM patients and to investigate whether the prognostic role of RAS mutation is altered with age. METHODS: We retrospectively investigated consecutive patients at our institution who underwent initial liver resection between 2006 and 2020. The inverse probability of treatment weighting (IPTW) method was used to balance the confounders among early- (≤45 years; EOCRLM), intermediate- (46-70 years; IOCRLM), and late-onset (>70 years; LOCRLM) groups. The prognostic role of RAS was assessed based on age group. RESULTS: A total of 1189 patients were enrolled: 162 in the EOCRLM group, 930 in the IOCRLM group, and 97 in the LOCRLM group. No difference in disease-free survival (DFS) was found between the three groups. However, EOCRLM were more likely to develop extrahepatic and extrapulmonary metastasis and had significantly lower five-year OS rates than IOCRLM. After IPTW, EOCRLM remained a negative prognostic predictor. RAS mutations were significantly associated with worse survival than wild-type RAS in EOCRLM and IOCRLM. However, RAS mutation did not predict the prognosis of patients with LOCRLM. CONCLUSIONS: Patients with EOCRLM had a significantly lower OS than IOCRLM patients and age influences the prognostic power of RAS status. These findings may be helpful for doctors to guide the clinical treatments and develop follow-up strategies.

Irinotecan- vs oxaliplatin-based regimens for neoadjuvant chemotherapy in colorectal liver metastasis patients: A retrospective study.

BACKGROUND: Neoadjuvant chemotherapy (NC) improves the survival outcomes of selected patients with colorectal liver metastasis (CRLM). The benefits of irinotecan-based regimens in these patients are still under debate. AIM: To compare the benefits of irinotecan- and oxaliplatin-based regimens in patients with resectable CRLM. METHODS: From September 2003 to August 2020, 554 patients received NC and underwent hepatectomy for CRLM. Based on a 1:1 propensity score matching (PSM) model, 175 patients who received irinotecan were matched to 175 patients who received oxaliplatin to obtain two balanced groups regarding demographic, therapeutic, and prognostic characteristics. RESULTS: Chemotherapy was based on oxaliplatin in 353 (63.7%) patients and irinotecan in 201 (36.3%). After PSM, the 5-year progression-free survival (PFS) and overall survival (OS) rates with irinotecan were 18.0% and 49.7%, respectively, while the 5-year PFS and OS rates with oxaliplatin were 26.0% and 46.8%, respectively. Intraoperative blood loss, operating time, and postoperative complications differed significantly between the two groups. In the multivariable analysis, carbohydrate antigen 19-9, RAS mutation, response to NC, tumor size > 5 cm, and tumor number > 1 were independently associated with PFS. CONCLUSION: In NC in patients with CRLM, irinotecan is similar to oxaliplatin in survival outcomes, but irinotecan is superior regarding operating time, intraoperative blood loss, and postoperative complications.

Perioperative Glucocorticoids are Associated with Improved Recurrence-Free Survival After Pancreatic Cancer Surgery: A Retrospective Cohort Study with Propensity Score-Matching.

PURPOSE: Perioperative anesthetic management may affect long-term outcome after cancer surgery. This study investigated the effect of perioperative glucocorticoids on long-term survival in patients after radical resection for pancreatic cancer. METHODS: In this retrospective cohort study with propensity score-matching, patients who underwent radical resection for pancreatic cancer from January 2005 to December 2016 were recruited. Baseline and perioperative data including use of glucocorticoids for prevention of postoperative nausea and vomiting were collected. Patients were followed up by qualified personnel for cancer recurrence and survival. The primary outcome was the recurrence-free survival. Outcomes were compared before and after propensity matching. The association between perioperative glucocorticoid use and recurrence-free survival was analyzed with multivariable regression models. RESULTS: A total of 215 patients were included in the study; of these, 112 received perioperative glucocorticoids and 103 did not. Patients were followed up for a median of 74.0 months (95% confidence interval [CI] 68.3-79.7). After propensity score-matching, 64 patients remained in each group. The recurrence-free survivals were significantly longer in patients with glucocorticoids than in those without (full cohort: median 12.0 months [95% CI 6.0-28.0] vs 6.9 months [4.2-17.0], P<0.001; matched cohort: median 12.0 months [95% CI 5.8-26.3] vs 8.3 months [4.3-18.2], P=0.015). After correction for confounding factors, perioperative glucocorticoids were significantly associated with prolonged recurrence-free survivals (full cohort: HR 0.66, 95% CI 0.48-0.92, P=0.015; matched cohort: HR 0.54, 95% CI 0.35-0.84, P=0.007). CONCLUSION: Perioperative use of low-dose glucocorticoids is associated with improved recurrence-free survival in patients following radical surgery for pancreatic cancer.

Mutated DNA Damage Repair Pathways Are Prognostic and Chemosensitivity Markers for Resected Colorectal Cancer Liver Metastases.

Deficiency of the DNA damage repair (DDR) signaling pathways is potentially responsible for genetic instability and oncogenesis in tumors, including colorectal cancer. However, the correlations of mutated DDR signaling pathways to the prognosis of colorectal cancer liver metastasis (CRLM) after resection and other clinical applications have not been fully investigated. Here, to test the potential correlation of mutated DDR pathways with survival and pre-operative chemotherapy responses, tumor tissues from 146 patients with CRLM were collected for next-generation sequencing with a 620-gene panel, including 68 genes in 7 DDR pathways, and clinical data were collected accordingly. The analyses revealed that 137 of 146 (93.8%) patients had at least one mutation in the DDR pathways. Mutations in BER, FA, HRR and MMR pathways were significantly correlated with worse overall survival than the wild-types (P < 0.05), and co-mutated DDR pathways showed even more significant correlations (P < 0.01). The number of mutated DDR pathways was also proved an independent stratifying factor of overall survival by Cox multivariable analysis with other clinical factors and biomarkers (hazard ratio = 9.14; 95% confidence interval, 1.21-68.9; P = 0.032). Additionally, mutated FA and MMR pathways were positively and negatively correlated with the response of oxaliplatin-based pre-operative chemotherapy (P = 0.0095 and 0.048, respectively). Mutated DDR signaling pathways can predict pre-operative chemotherapy response and post-operative survival in CRLM patients.

Clinicopathologic and Prognostic Significance of Carboxyl Terminus of Hsp70-interacting Protein in HBV-related Hepatocellular Carcinoma.

BACKGROUND: Many factors, including molecular ones, were demonstrated to be associated with long-term prognosis of hepatocellular carcinoma (HCC). Thus far, the expression and clinicopathologic and prognostic significance of the carboxyl terminus of Hsp70-interacting protein (CHIP) in B-type hepatitis virus (HBV)- related HCC remain unknown. MATERIALS AND METHODS: CHIP expression was detected by immunohistochemical staining of surgical samples from 79 patients with HCC with HBsAg positivity. In addition, correlations with clinicopathologic parameters and patient survival were evaluated. RESULTS: It was found that positive CHIP staining was observed in tumor, but not non-tumor, tissues. High expression of CHIP was significantly related to larger tumor size, with marginally significant associations noted for presence of portal vein invasion and higher serum a-fetoprotein level. In addition, univariate analysis showed that high CHIP expression was a powerful predictor for dismal overall and disease-free survival. However, independent prognostic implications of CHIP were not proven in multivariate Cox regression test. CONCLUSIONS: CHIP is overexpressed in HBV-related HCC and is associated with unfavorable biological behavior as well as poor prognosis. However, its prognostic role needs to be further validated.