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.

Circulating Lipid- and Inflammation-Based Risk (CLIR) Score: A Promising New Model for Predicting Outcomes in Complete Colorectal Liver Metastases Resection.

BACKGROUND: Colorectal cancer liver metastasis (CRLM) is a determining factor affecting the survival of colorectal cancer (CRC) patients. This study aims at developing a novel prognostic stratification tool for CRLM resection. METHODS: In this retrospective study, 666 CRC patients who underwent complete CRLM resection from two Chinese medical institutions between 2001 and 2016 were classified into the training (341 patients) and validation (325 patients) cohorts. The primary endpoint was overall survival (OS). Associations between clinicopathological variables, circulating lipid and inflammation biomarkers, and OS were explored. The five most significant prognostic factors were incorporated into the Circulating Lipid- and Inflammation-based Risk (CLIR) score. The predictive ability of the CLIR score and Fong's Clinical Risk Score (CRS) was compared by time-dependent receiver operating characteristic (ROC) analysis. RESULTS: Five independent predictors associated with worse OS were identified in the training cohort: number of CRLMs >4, maximum diameter of CRLM >4.4 cm, primary lymph node-positive, serum lactate dehydrogenase (LDH) level >250.5 U/L, and serum low-density lipoprotein-cholesterol (LDL-C)/high-density lipoprotein-cholesterol (HDL-C) ratio >2.9. These predictors were included in the CLIR score and each factor was assigned one point. Median OS for the low (score 0-1)-, intermediate (score 2-3)-, and high (score 4-5)-risk groups was 134.0 months, 39.9 months, and 18.7 months in the pooled cohort. The CLIR score outperformed the Fong score with superior discriminatory capacities for OS and RFS, both in the training and validation cohorts. CONCLUSIONS: The CLIR score demonstrated a promising ability to predict the long-term survival of CRC patients after complete hepatic resection.

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.

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.

Development of a model to predict pathologic response to chemotherapy in patients with colorectal liver metastases.

BACKGROUND: Preoperative chemotherapy has widely been used in colorectal cancer liver metastasis (CRLM). Pathological response to chemotherapy is very important in evaluating tumor biology. However, there is still a lack of a non-invasive and accurate method to evaluate pathological response before surgery. METHODS: We retrospectively analyzed the clinicopathologic data of patients with CRLM who underwent liver resection after preoperative chemotherapy between January 2006 and December 2018. Pathological responses were defined as minor when there are ≥50% remnant viable cells and as major when 0-49% remnant viable cells exist. RESULTS: A total of 482 patients were included and randomly divided into training (n=241) and validation (n=241) cohorts. The proportion of major pathologic response was similar between the two groups (51.5% and 48.5%). Multivariate analysis determined the disease-free interval (DFI), tumor size, tumor number, and RAS status as independent predictors of major pathologic response to preoperative chemotherapy. The nomogram incorporating these variables showed good concordance statistics in the training cohort (0.746, 95% CI: 0.685-0.807) and validation cohort (0.764, 95% CI: 0.704-0.823). In addition, the nomogram showed good applicability in patients with different characteristics. CONCLUSIONS: The established nomogram model performed well in predicting pathological response in patients with CRLM.

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.

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.

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.

The characteristics and long-term survival of patients with colorectal liver metastases with pathological complete response after chemotherapy.

Purpose: Preoperative chemotherapy is widely used for colorectal liver metastasis (CRLM). Pathological complete response (PCR) after chemotherapy indicates complete tumor regression and an extremely favorable prognosis. This study aimed to explore the characteristics and long-term survival of CRLM patients with pCR, who underwent surgery after preoperative chemotherapy. Methods: We retrospectively analyzed the clinical data of 494 CRLM patients who underwent hepatectomy after preoperative chemotherapy between January 2006 and January 2019. pCR was defined as the absence of any cancer cells on pathological examination. Results: Thirty (6.07%) patients achieved pCR after preoperative chemotherapy; 70% patients who achieved pCR did not experience recurrence and were cured after hepatectomy. The long-term prognosis of patients with pCR was extremely favorable, with 10-year overall and disease-free survivals of 85.2% and 73.7%, respectively; these were significantly better than those of patients without pCR (31.3% and 15.2%, respectively). Liver metastases <3 cm, preoperative carcinoembryonic antigen level ≤20 ng/mL, primary T stage 1-2, and right-sided primary tumors were independent predictors for pCR. Conclusion: pCR occurred in 6% of patients with CRLM after preoperative chemotherapy. Patients with a smaller tumor burden are more likely to benefit from chemotherapy and achieve pCR.

Indocyanine Green Clearance Test for the Preoperative Assessment of Chemotherapy-Related Hepatic Injury in Patients with Colorectal Liver Metastasis.

PURPOSE: The aim of the present study was to determine the value of the indocyanine green (ICG) clearance test in the preoperative assessment of chemotherapy-related hepatic injury in patients with liver metastasis from colorectal cancer. METHODS: A total of 218 patients who underwent hepatic dissection due to colorectal cancer liver metastasis at the Peking University Cancer Hospital between January 2016 and December 2017 were retrospectively evaluated; 179 patients who received chemotherapy prior to hepatic resection were further examined. Patient- and chemotherapy-related factors were analyzed in both groups with normal and abnormal ICG retention rate at 15 min (ICG-R15), and their intraoperative and postoperative outcomes were compared. RESULTS: The chemotherapy group had a higher mean ICG-R15 value and a higher number of patients who exhibited abnormal ICG-R15, compared with the no-chemotherapy group. Under the guidance of ICG test, no patients experienced severe complications in the abnormal ICG-R15 group compared with the normal ICG-R15 group, and the overall morbidity was also not significantly different between the two groups. However, the incidence of severe complications was higher in patients who underwent major resection with a normal ICG-R15 value compared with patients with an abnormal ICG-R15 value who underwent minor resection (P<0.05). Multivariable logistic regression analyses revealed that body mass index (BMI) ≥28 and oxaliplatin use were independent predictors of abnormal ICG-R15. The ICG-R15 value was significantly higher in the two-risk factors group compared with the no-risk factor group (P=0.012), but not statistically different compared with the one risk factor group. CONCLUSION: Screening of patients with chemotherapy-associated liver injury using the IGC test may help in performing safe hepatectomy by avoiding major resection. BMI ≥28 and oxaliplatin use were independent preoperative predictors of abnormal ICG-R15.

Sub-millimeter surgical margin is acceptable in patients with good tumor biology after liver resection for colorectal liver metastases.

BACKGROUND: The definition of R1 resection in colorectal cancer liver metastases (CRLM) remains debatable. This retrospective study was conducted to clarify the impact of R1 margin on patient survival after liver resection for CRLM, taking into consideration tumor biology, including RAS status and chemotherapy response. METHODS: We retrospectively analysed the clinical and survival data of 214 CRLM patients with initially resectable liver metastases who underwent liver resection after receiving neoadjuvant chemotherapy between January 2006 and December 2016. RESULTS: R1 resection significantly impacted patients' overall survival (OS) and disease-free survival (DFS) in the overall patient cohort (5-year OS: 53.2% for R0 vs 38.2% for R1, P = 0.001; 5-year DFS: 26.5% for R0 vs 10.5% for R1, P = 0.002). In the RAS wild-type subgroup and respond to chemotherapy (RC) subgroup, R1 reached a similar OS to those who underwent R0 resection (RAS wild-type, P = 0.223; RC, P = 0.088). For the RAS mutated subgroup and no response to chemotherapy (NRC) subgroup, OS was significantly worse underwent R1 resection (RAS mutant, P = 0.002; NRC, P = 0.022). When considering tumor biology combining RAS and chemotherapy response status, R1 resection was only acceptable in patients with both RAS wild-type and RC (5-year OS: 66.4% for R0 vs 65.2% for R1, p = 0.884), but was significantly worse in those with either RAS mutation or NRC. CONCLUSIONS: Tumor biology plays an important role in deciding the appropriate resection margin in patients with CRLM undergoing radical surgery. R1 resection margin is only acceptable in RAS wild-type patients who respond to chemotherapy.

Radiofrequency ablation versus resection for technically resectable colorectal liver metastasis: a propensity score analysis.

BACKGROUND: Liver resection is the first-line treatment for patients with resectable colorectal liver metastasis (CRLM), while radiofrequency ablation (RFA) can be used for small unresectable CRLM because of disease extent, poor anatomical location, or comorbidities. However, the long-term outcomes are unclear for RFA treatment in resectable CRLM. This study aimed to compare the recurrence rates and prognosis between resectable CRLM patients receiving either liver resection or RFA. METHODS: Consecutive patients who underwent RFA or hepatic resection from November 2010 to December 2015 were assigned in this retrospective study. Propensity score analysis was used to eliminate baseline differences between groups. Survival and recurrence rates were compared between patients receiving liver resection and RFA. RESULTS: With 1:2 ratio of propensity scoring, 46 patients in the RFA group and 92 in the resection group were successfully matched. Overall survival was similar between the two groups, but the resection group had a higher disease-free survival (median, 22 months vs. 14 months). Whereas among patients with a tumor size of ≤ 3 cm, disease-free survival was similar in the two groups (median, 24 months vs. 21 months). Compared to the resection group, the RFA group had a higher rate of intrahepatic recurrence (34.8% vs. 12.0%) and a shorter recurrence free period. The local and systemic recurrence rate and recurrence-free period for the same were insignificant in the two groups. Poor disease-free survival was associated with RFA, T4, tumor diameter > 3 cm, and lymph node positivity. CONCLUSION: Among patients with technically resectable CRLM, resection provided greater disease-free survival, although both treatment modalities provided similar overall survival.

The impact of primary tumour location in patients undergoing hepatic resection for colorectal liver metastasis.

BACKGROUND: Primary tumour location has long been debated as a prognostic factor in colorectal cancer patients with liver metastases (CRLM) undergoing liver resection. This retrospective study was conducted to clarify the prognostic value of tumour location after radical hepatectomy for CRLM and its underlying causes. METHODS: We retrospectively analysed clinical data from 420 patients with CRLM whom underwent liver resection between January 2002 and December 2015. Right-sided (RS) tumours include tumours located in the cecum, ascending colon, and transverse colon, and left-sided (LS) tumours include those located in the splenic flexure, descending colon, sigmoid colon, and rectum. RESULTS: Both overall survival (OS) and disease-free survival (DFS) were similar between patients with RS and LS primary tumours (5-year OS: 46.5% vs 38.3%, P = 0.699; 5-year DFS: 29.1% vs 22.4%, P = 0.536). Specifically, RAS mutation rate was significantly higher in patients with RS tumours (P = 0.007). Subgroup analysis showed that the RAS mutation on the LS and RS tumours have different prognostic impact for CRLM patients on long-term survival after hepatic resection (RS, OS: P = 0.437, DFS: P = 0.471; LS, OS: P < 0.001, DFS: P = 0.002). The multivariable analysis showed that RAS mutant is an independent factor influencing OS in patients with LS primary tumour only. CONCLUSIONS: The site of the primary tumour has no significant impact on the long-term survival in patients with CRLM undergoing radical surgery. However, prognostic value of RAS status differs depending on the site of the primary tumour.

Long-term postoperative survival prediction in patients with colorectal liver metastasis.

Numerous factors affect the prognosis of colorectal liver metastasis (CRLM) patients after hepatic resection. We investigated several factors related to overall survival in patients with CRLM to identify those most likely to benefit from hepatic resection, and produced a rational tumor biology score system. Three hundred CRLM patients treated with preoperative chemotherapy followed by hepatic resection between 2006 and 2016 were enrolled in our study. Clinicopathologic and long-term survival data were collected and assessed. Patient 1-, 3-, and 5-year overall survival rates were 92.7%, 58.3%, and 45.8%, respectively, while 1-, 3-, and 5-year disease-free survival rates were 44.7%, 28.6%, and 24.2%, respectively. Multivariate Cox regression analysis revealed poor preoperative chemotherapy response, Fong clinical risk score > 2, and KRAS mutation to be independent prognostic indicators in CRLM patients. As part of a preoperative staging system in which one point was assigned for each factor, a total score (out of 3) was predictive of long-term survival following surgery. These factors facilitate personalized prognostic assessments in CRLM patients planning for resection.

Survival prediction in patients with resectable colorectal liver metastases: Clinical risk scores and tumor response to chemotherapy.

Clinical risk scores and response to pre-operative chemotherapy are prognostic factors of colorectal liver metastases. The aim of the present study was to evaluate the effectiveness of combining these factors to predict patient survival and to select patients for curative therapy. The study included 189 patients who underwent hepatectomy following neo-adjuvant chemotherapy, for initially resectable colorectal liver metastases, between January 2005 and December 2015. Patients were stratified into four sub-groups: A1-2, low clinical risk scores with/without a response to pre-operative chemotherapy; and B1-2, high clinical risk scores with or without a response to pre-operative chemotherapy. Treatment and survival data were analysed. Survival was significantly longer in patients with low clinical risk scores and a response to pre-operative chemotherapy; these factors were confirmed as independent prognostic factors by multivariate analysis. Combining clinical risk score and chemotherapy response classification, patient survival was significantly longer for groups A1-2/B1 compared with for group B2, in which only 10.2% of patients were alive after 5 years. Of those with no response to first-line chemotherapy, survival was significantly longer in patients who responded to second-line chemotherapy. A combined clinical risk score and chemotherapy response classification may aid in identifying suitable candidates for potentially curative therapy.

Role of a liver-first approach for synchronous colorectal liver metastases.

AIM: To evaluate the feasibility and survival outcomes of a liver-first approach. METHODS: Between January 2009 and April 2013, 18 synchronous colorectal liver metastases (sCRLMs) patients with a planned liver-first approach in the Hepatopancreatobiliary Surgery Department I of the Beijing Cancer Hospital were enrolled in this study. Clinical data, surgical outcomes, morbidity and mortality rates were collected. The feasibility and long-term outcomes of the approach were retrospectively analyzed. RESULTS: Sixteen patients (88.9%) completed the treatment protocol for primary and liver tumors. The main reason for treatment failure was liver disease recurrence. The 1 and 3 year overall survival rates were 94.4% and 44.8%, respectively. The median survival time was 30 mo. The postoperative morbidity and mortality were 22.2% and 0%, respectively, following a hepatic resection, and were 18.8% and 0%, respectively, after a colorectal surgery. CONCLUSION: The liver-first approach appeared to be feasible and safe. It can be performed with a comparable mortality and morbidity to the traditional treatment paradigm. This approach might offer a curative opportunity for sCRLM patients with a high liver disease burden.

Screening of susceptibility genes and multi-gene risk analysis in gastric cancer.

The aim of the study was to explore the relations between the genetic polymorphism and the susceptibility to the gastric cancer in Chinese Han population, and to analyze the multi-genes risk in the development of gastric carcinoma. A case-control study of 1:1 matching was performed on 564 individuals with primary gastric carcinoma in Nanjing, China. The genotypes of CYP2E1, GSTMl, GSTTl, NAT2, ALDH2, MTHFR, XRCCl, IL-1ß, VDR, and TNF were detected by molecular biological techniques (PCR-RFLP and AS-PCR). Sole gene and gene-gene interactions were analyzed using Logistic regression model. The effect of multi-genes on gastric carcinoma was analyzed using multi-gene risk analysis model, which focused on the effect of multi-gene interaction on the development of gastric carcinoma. The genotypes involved in the susceptibility of gastric carcinoma were CYP2E1(c1/c1), NAT2M1(T/T), NAT2M2(A/A), XRCC1194(T/T), NAT2 phenotype (slow acetylator), MTHFR1298(A/C), and VDR TaqI(T/T), respectively. Multi-gene risk analysis model was introduced to analyze the effect of these genes on the gastric carcinoma. The results showed that there was a strong relation between odds ratio (OR) value of polygene combination and the gene frequency. With the increase of susceptibility gene frequency, the risk distribution curve of gastric carcinoma would shift to a more dangerous phase and exhibit a quantitative relation. Our results demonstrated that the OR of each gene can be utilized as an index to assess the effect of multiple susceptible genes on the occurrence of gastric carcinoma.

The outcome of liver resection and lymphadenectomy for hilar lymph node involvement in colorectal cancer liver metastases.

OBJECTIVE: Hepatic hilar lymph node (HLN) involvement is considered as a poor prognostic factor during liver resection in colorectal liver metastases (CLM). The purpose of this study is to identify the clinical factors that distinguish HLN-positive patients from those who are hilar lymph node negative and to evaluate the frequency of macroscopic involvement of hepatic HLN, to investigate the impact of HLN involvement on survival after resection for CLM with lymphadenectomy and adjuvant chemotherapy. PATIENTS AND METHODS: Between January 2000 and August 2012, 73 selected CLM patients underwent liver resections with lymphadenectomy in the Hepatopancreatobiliary Surgery Department I of Beijing Cancer Hospital. Clinical data, surgical outcome, and prognosis after operation of patients with HLN involvement were compared with that of patients without HLN involvement. RESULTS: Of the 73 patients who underwent liver resections with lymphadenectomy, 12 (16.4 %) patients had HLN involvement identified by pathology. Compared with patients without HLN involvement, the frequency of lymph nodes metastasis for primary tumor was significantly higher in HLN-positive patients (p = 0.023). For CLM patients with and without HLN involvement, 5-year overall survival (OS) was 16.2 and 37.1 %, respectively (p = 0.04). Five-year disease-free survival (DFS) rates were 0 and 32.9 % (p = 0.034). Multivariate analysis showed that involved resected HLN was an independent risk factor for overall survival. CONCLUSION: We should suspect HLN involvement in patients with colorectal cancer liver metastases when they have regional lymph nodes of primary tumor metastasis. Liver resection with HLN dissection might offer a unique curative opportunity for CLM patients with HLN involvement.

[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.