Table of Content

30 June 2024, Volume 11 Issue 2

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Special topic

Prognosis and risk factors of different recurrence patterns after hepatectomy for colorectal liver metastasis

Chen Hanwei, Li Lei

2024, 11(2):  27-32. 

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Objective: To study the prognostic differences and risk factors of different recurrence patterns after hepatectomy for colorectal liver metastasis.
Methods: The general data, clinical data and follow-up data of patients with colorectal liver metastasis who underwent hepatectomy in the Department of General Surgery of Peking University Third Hospital from January 2009 to February 2023 were collected. Kaplan-Meier curve was used to analyze the survival differences between different recurrence times and different recurrence sites. The maximally selected test was used to find the optimal cut-off value of recurrence time for distinguishing the survival after recurrence. Logistic regression analysis were used to analyze the risk factors of early recurrence.
Results: A total of 281 patients met the inclusion and exclusion criteria. There were statistically significant differences in mortality and overall survival between patients with and without postoperative recurrence (P=0.001). The optimal cut-off value for distinguishing early and late recurrence was 12 months (P=0.001). There was a statistically significant difference in the post-recurrence survival between patients with early recurrence and late recurrence (P=0.001 1). There was a statistically significant difference in the post-recurrence survival between different recurrence sites (P=0.002 3), and the prognosis of patients with the first recurrence site in the lung was the best. Logistic regression analysis showed that patients with positive lymph node metastasis of primary tumor (OR=2.294, 95%CI:1.171-4.496, P=0.019), preoperative CEA≥5.31 ng/ml (OR=2.160, 95%CI:1.001-4.660, P=0.049 8) and preoperative CA19-9≥ 40.52 U/ml (OR=2.210, 95%CI:1.030-4.741, P=0.042) were at high risk of early recurrence after surgery.
Conclusions: The recurrence within 12 months and extrapulmonary recurrence is associated with poor prognosis. The risk factors for early recurrence include positive lymph node metastasis of primary tumor, preoperative CEA≥5.31 ng/ml and preoperative CA19-9≥ 40.52 U/ml. Patients with related risk factors should be actively reviewed and monitored.

Analysis of clinical features of multiple primary tumors associated with liver cancer

Wu Wenqi, Wang Hao, Wang Yuxia

2024, 11(2):  33-36. 

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Objective: To explore the clinical epidemiological characteristics and survival outcomes of patients with multiple primary malignant tumors (MPMTs) combined with liver cancer.
Methods: From August 2010 to June 2023, patients with liver cancer were selected from malignant tumor patients admitted to the Cancer Center of Peking University Third Hospital. The basic information of the patients and the incidence information of liver cancer and other tumors were collected to make comparisons between MPMTs and single liver cancer, also groups with liver cancer as the first or the second primary cancer.
Results: The incidence of liver cancer combined with extraneous tumors was accounting for 13.1% (23/176) of liver cancer patients during the same period. Among the patients, 5 had synchronous multiple primary tumors, and 18 had metachronous multiple primary tumors. Of these patients, 9 had liver cancer as the first primary tumor, and 9 had liver cancer as the second primary tumor. Liver cancer patients with family history of cancer were more likely to have multiple primary tumors (χ²=5.22, P=0.030). Liver cancer as the first primary tumor had a shorter interval for multiple primary tumor onset compared to liver cancer as the second primary tumor (35 month vs. 156 month, P=0.009). The onset interval was negatively correlated with the diagnosis age of the first primary tumor (r=-0.60, P=0.009).
Conclusions: Multiple primary tumors associated with liver cancer tend to occur in patients with a family history of cancer. There was a difference in the tumor incidence interval between multiple primary cancers with liver cancer as the first primary tumor and multiple primary cancers with liver cancer as the second primary tumor.

Effect of hepatic R1 margin on intrahepatic recurrence of colorectal cancer liver metastases

Ai Xiangnan, Wang Hangyan, Zhang Wenxuan, Jin Changguo, Wu Zhenyu, Xiu Dianrong

2024, 11(2):  37-42. 

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Objective: The effect of R1 margin on liver resection for colorectal cancer liver metastasis (CRLM) has been controversial, and there is a lack of models for the effect of hepatic R1 margin on intrahepatic margin recurrence. This study aimed to construct a predictive model for intrahepatic margin recurrence in CRLM patients to understand whether there is an effect of R1 margin on intrahepatic margin recurrence.
Methods: The data of 123 CRLM patients undergoing surgical treatment in the General Surgery Department of Peking University Third Hospital from January 2009 to December 2020 were retrospectively analyzed, and the factors with independent predictive value for intrahepatic margin recurrence were established through binary Logistic regression analysis, and the predictive model was established.
Results: The whole cohort had 48 (39.0%) and 75 (61.0%) non-hepatic recurrence.73 (59.3%) of R0 resection and 50 (40.7%) of R1 resection. In the univariate regression analysis, the maximum diameter of metastases (OR=2.396, P=0.041), non-anatomical resection (OR=3.732, P=0.025), operation duration (OR=2.571, P=0.013), liver R1 margin (OR=2.907, P=0.005) were significantly associated with hepatic R. margin recurrence. After multivariate regression analysis, R1 margin was no longer statistically significant (OR=2.103, 95%CI: 0.94-4.65, P=4.70), while metastasis with maximum diameter >21 mm (OR=2.509, 95%CI: 1.02-6.17, P=0.045) and non-anatomical resection (OR=3.585, 95%CI: 1.06-12.15, P=0.040) had independent predictive value for intrahepatic margin recurrence.
Conclusions: The R1 margin in the model established in this study seemed to increase the risk of intrahepatic margin recurrence, but did not reach statistical significance. Independent risk factors affecting intrahepatic margin recurrence were the maximum diameter of hepatic metastases and non-anatomical resection.

Clinical and pathological factors affecting the prognosis of patients with colorectal liver metastasis

Wang Peng, Du Jundong, Wang Hangyan, Xiu Dianrong

2024, 11(2):  43-47. 

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Objective: To investigate the clinical and pathological factors affecting the prognosis of patients with colorectal liver metastases (CRLM) patients.
Method: Patients with synchronous CRLM who were admitted to Peking University Third Hospital from March 2014 to March 2016 were retrospectively analyzed. The relevant clinical data, pathology of primary tumor and liver metastases of each patient were collected, and the patients were followed up. Univariate analysis and Cox regression were used to analyze the independent prognostic factors of CRLM.
Result: A total of 97 patients with CRLM were included in this study, including 57 males and 40 females, with an average age of (61.2±11.8) years, 54 cases in the right colon and 43 cases in the left colon and rectum. Univariate analysis showed that preoperative carcinoembryonic antigen (CEA)>32 ng/ml, preoperative carbohydrate antigen19-9 (CA19-9)>20 U/ml, presence of cancer nodules, postoperative N stage, primary tumor located in the right hemicolon, the number of liver metastases>3, and poor differentiation of the primary tumor were non-independent risk factors affecting the 3-year overall survival of patients (all P<0.05). Cox regression model was used for multivariate analysis, the results showed that preoperative CEA level (hazard ratio [HR]=2.123, 95% confidence interval [95%CI]: 1.151-3.918), preoperative CA19-9 level (HR=2.022, 95%CI: 1.094-3.738), primary tumor location (HR=0.502, 95%CI: 0.265-0.951) and tumor differentiation (HR=0.519, 95%CI: 0.300-0.899) were independent risk factors for prognosis.
Conclusion: The primary tumor located in the right hemicolon, the primary tumor poorly differentiated, the preoperative CEA >32 ng/ml, and the preoperative CA19-9 >20 U/ml are independent risk factors affecting the prognosis of patients with CRLM.

The overexpression of miRNA-10a promotes liver regeneration in rats with liver cirrhosis after hepatectomy

Yu Zhencen, Gu Xiaohui, Liu Chao, Wang Xin

2024, 11(2):  48-52. 

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Objective: To investigate the effect of miRNA-10a on liver regeneration in rats after liver resection in liver cirrhosis.
Methods: Thirty-six cirrhotic rats were randomly divided into a sham operation group (Group A, n=12), a 70% liver resection without transfection group (Group B, n=12), and a 70% liver resection with transfection group (Group C, n=12). Two weeks before surgery, successful hepatocyte-specific transfection of miRNA-10a was performed in rats of Group C. At 12h, 24h, 48h, and 72h after surgery, 3 rats from each group were euthanized, and blood samples from the portal vein were collected for testing serum liver function indicators including alanine aminotransferase (ALT) and albumin (ALB). The levels of miRNA-10a in liver tissue were detected using PCR, and the liver-to-body weight ratio was calculated at different time points.
Results: At 12 h, 24 h, 48 h, and 72 h after surgery, the levels of miRNA-10a in liver tissue of Group C rats were significantly higher than the other two groups, indicating successful overexpression of miRNA-10a. At 12 h, 24 h, 48 h, and 72 h after surgery, the serum ALT levels of Group C rats were lower on average than Group B, while the ALB levels were higher on average than Group B, suggesting that miRNA-10a is beneficial for protecting liver function. At 48 h and 72 h after surgery, the liver-to-body weight ratio of Group C rats was significantly higher than Group B, indicating that overexpression of miRNA-10a promotes liver tissue growth.
Conclusion: Overexpression of miRNA-10a promotes liver regeneration in rats with liver cirrhosis after hepatectomy.

Original article

Global liver and gallbladder cancer incidence and mortality in 2022 and projections to 2050

Liu Manqi, Xu Mengyuan, Shan Tianhao, Zhao Hong, Zeng Hongmei, Cai Jianqiang

2024, 11(2):  53-60. 

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Objective: To analyze the global epidemiological profiles of liver and gallbladder cancer in 2022, and project the global burden of cancer incidence and mortality until 2050.
Methods: Based on the GLOBOCAN 2022 database, we analyzed the global burden of liver and gallbladder cancer in 2022 and the projected disease burden in 2050. We calculated age-standardized incidence rates (ASIRs) and age-standardized mortality rates (ASMRs) by using Segi's world standard population structure data. We estimated the future number of cases and deaths by 2050 based on world population prospects.
Results: In 2022, there were an estimated 866,136 new cases and 758,725 deaths from liver cancer, corresponding to ASIRs and ASMRs of 8.6 per 100,000 and 7.4 per 100,000, respectively. There were an estimated 122,491 new cases and 89,055 deaths from gallbladder cancer, corresponding to ASIRs and ASMRs of 1.2 per 100,000 and 0.83 per 100,000, respectively. Incidence and mortality rates of liver cancer were higher in males than in females across different age groups, and gallbladder cancer displayed higher rates among females compared to males. The country with the highest ASIR and ASMR for liver cancer was Mongolia. For gallbladder cancer, Bolivia reported the highest ASIR and ASMR. By 2050, the annual number of new cases and deaths from liver cancer will increase to 1,564,034 (an 80.6 percent increase from the year 2022) and 1,420,926 (an 87.3 percent increase), respectively. The annual number of new cases and deaths from gallbladder cancer will increase to 235,096 (a 91.9 percent increase from the year 2022) and 176,725 (a 98.4 percent increase), respectively. Africa has the largest increase in both projected new cases and deaths from liver and gallbladder cancer globally in 2050.
Conclusions: Inequities in liver and gallbladder disease burden persist worldwide. Regions such as Asia and Africa, as well as countries such as Mongolia and Bolivia, which face heavy disease burden and rising incidence rates, must prioritize the establishment of cancer control initiatives.

Efficacy and safety of bevacizumab with nab-paclitaxel and tegafur gimeracil oteracil potassium capsule (S-1) in advanced biliary tract adenocarcinoma

Zhang Chao, Sun Yongkun, Su Aijiang, Zhao Jianjun, Zhou Jianguo, Li Zhiyu, Zhou Hua, Zhao Pan, Chen Nan, Liu Na

2024, 11(2):  61-65. 

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Objective: To evaluate the efficacy and safety of bevacizumab with nab-paclitaxel and tegafur gimeracil oteracil potassium capsule (S-1) in advanced biliary tract adenocarcinoma patients.
Method: Totally 22 stageⅣ biliary tract adenocarcinoma patients were enrolled in this single arm, single center prospective phaseⅡ study. Patients were treated with bevacizumab at a dose of 5 mg/kg on day 1, nab-paclitaxel at a dose of 150 mg/m² on day 1 and S-1, 40 to 60 mg bid/day on days 1-10 of a 14-day cycle. Treatments were repeated until disease progression or unacceptable toxicity occurred. The primary endpoint was objective response rate (ORR). The secondary endpoints were median progression-free survival (PFS), disease control rate (DCR), and adverse events (AEs).
Result: The number of patients enrolled were 22, and 21 patients were evaluated for efficacy, with a median of 6 cycles of treatment and a median of 2 lines of treatment. A total of 9 patients achieved partial response (PR) with an ORR of 42.9%(9/21), DCR was 85.7%(18/21). 3 progressive disease was observed. The median PFS were 8 months (95% confidence interval [95%CI]: 4.5~11.5). The incidence of grade 3 treatment-related adverse events in 22 patients was 68.2%(15/22), and there were no grade 4 treatment-related adverse events. The most common grade 3 or 4 toxicities were neutropenia (18.1%), Thrombocytopenia in 2 cases (9.1%), gastrointestinal reaction in 2 cases (9.1%), increased total bilirubin (TBIL)/direct bilirubin (DBIL) in 1 case (4.5%), anemia in 1 case (4.5%), others including neurotoxicity, elevated aminotransferase, bleeding, diarrhea, fatigue, elevation of blood pressure, proteinuria, etc., were grade 1 to 2. During treatment, 4 cases (18.1%) were combined with infection, 3 cases stopped treatment due to adverse events, and there were no treatment-related deaths.
Conclusion: The combination of bevacizumab with nab-paclitaxel and S-1 showed explicit antitumor activities and favorable safety profile in advanced biliary tract adenocarcinoma patients, which has good clinical therapeutic value.

The prognostic value of preoperative platelet to neutrophil ratio in colorectal cancer patients with resectable synchronous liver metastases

Zhang Jixin, Wu Liang, Wu Xueliang, Wang Likun, Ma Hongqing, Han Lei

2024, 11(2):  66-71. 

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Objective: To investigate the prognostic value of preoperative serum platelet to lymphocyte ratios (PLR) in colorectal cancer patients with synchronous liver metastases.
Methods: The 74 patients clinicopathological data of in colorectal cancer patients with synchronous liver metastases who underwent liver resection in First Affiliated Hospital of Hebei North University were collected retrospectively. The X-tile software was used to calculate the best cut-off value of PLR toward prognosis, and the patients were divided into low PLR group (n=31) and high PLR group (n=43) according to the aforementioned cut-off value. Differences in general clinicopathological data and prognosis of the two group patients were investigated.
Results: The best cut-off for PLR prognosis was 188, PLR≥188 was the high PLR group and PLR<188 was the low PLR group. Compared with patients in the low PLR group, the tumor stage of the high PLR group was later, the lymph node metastasis rate was higher, and the number of liver metastases was more (all P<0.05). The median survival time of patients in the high PLR group and the low PLR group were 33 months and 11 months (P=0.001), respectively. The Cox model multivariate analysis showed that pT staging (HR=2.199, 95%CI: 1.156-4.182, P=0.016), carcinoembryonic antigen ≥3.4 ng/ml (HR=1.834, 95%CI: 1.079-3.117, P=0.025), and PLR≥188 (HR=1.885, 95%CI: 1.022-3.477, P=0.042) were independent risk factors for the colorectal cancer patients with synchronous liver metastases. The prognostic prediction model was constructed according to the results of the survival analysis, and the validity curve and the receiver operation characteristic curve showed good model fit and accuracy.
Conclusions: Preoperative PLR is closely related to the poor prognosis of colorectal cancer patients with synchronous liver metastases. Patients with preoperative PLR≥188 have a worse prognosis. The survival prediction models is constructed based on PLR, T stage and carcinoembryonic antigen have high accuracy and can be used to guide clinical practice.

Review

Research progress in the treatment of unresectable intrahepatic cholangiocarcinoma

Zhang Yongqi, Li Zhao

2024, 11(2):  89-93. 

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Intrahepatic cholangiocarcinoma (ICC) is the second most common primary tumor in the liver, and radical surgical resection is currently the main way to cure ICC. But ICC has an insidious onset, rapid progression, and many have lost the opportunity for radical surgery when clinically found. Chemotherapy regimens such as gemcitabine combined with cisplatin are often used clinically to treat unresectable ICC, but the efficacy is often not satisfactory. The emergence of new therapies such as targeted therapy and immunotherapy has brought a new direction for the treatment of unresectable ICC. Through the study of the mechanism of ICC tumorigenesis, researchers have discovered potential targets for the treatment of ICC, and clinical drug trials for targets such as EGFR, VEGF, FGFR2, HER2, IDH1/2, BRAF, NTRK, MEK1/2 and other targets have made good progress. Trials of immune checkpoint inhibitors have also shown good efficacy in patients with ICC. The combination of the above therapies can also enable some patients to achieve tumor reduction and obtain surgical opportunities. This article reviews the recent research progress of treatment for unresectable ICC, in order to provide new ideas for the treatment of ICC.

Nursing field

Study on the development track of early fatigue after liver transplantation

Xi Shuangmei, Zhang Lili, Gu Yanmei, Guo Huimin, Liu Xin, Zheng Yulin, Jin Boxun, Li Guangming

2024, 11(2):  94-99. 

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Objective: To explore the development track of early fatigue after liver transplantation and its influencing factors.
Methods: 96 liver transplant patients who were followed up in the liver transplant center of our hospital from January 2019 to March 2023 were selected as the research objects. Fatigue assessment scale (FAI) was used to evaluate the fatigue of patients at 1 week, 2 weeks, 1 month, 3 months and 6 months after liver transplantation, and growth mixed model (LGMM) was used to analyze and identify the early fatigue development track of patients after liver transplantation. The general data, social support and psychological state of patients were collected, and the influencing factors of patients' early fatigue development track were analyzed by multi-classification Logistic regression.
Results: During the 6-month follow-up, there were 91 patients with complete follow-up data of FAI scale, and finally 91 patients were included. LGMM analysis showed that the early fatigue development trend of patients after liver transplantation was divided into three types, namely, descending group(n=36), stable group(n=34) and ascending group(n=21). The fatigue development of all three groups had a time effect. The FAI score of descending group decreased significantly with time, while that of stable group did not change significantly with time, while that of ascending group increased significantly with time. Logistic regression analysis showed that age, anxiety, depression, sleep status and social support level were the influencing factors of early fatigue development after liver transplantation (P<0.05).
Conclusion: The development track of early fatigue in patients after liver transplantation is heterogeneous, and there are different types of development trends, among which age, anxiety, depression, sleep state and social support level are the influencing factors.