Volume 33,Issue 7,2024 Table of Contents

1 Analysis of technical points in the process of liver parenchymal transection during laparoscopic hepatectomy

YOU Nan , ZHENG Lu

2024, 33(7):1029-1034. DOI: 10.7659/j.issn.1005-6947.2024.07.001

[Abstract](137) [HTML](172) [PDF 650.62 K](866)

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Liver resection is one of the most challenging procedures and technically advanced areas in abdominal surgery. With the development of minimally invasive surgical instruments, imaging equipment, and advances in surgical techniques, laparoscopic liver resection has entered a rapid development stage. However, it remains difficult and high-risk, with many technical considerations. One of the core aspects is the control of techniques during liver parenchymal transection, which mainly involves the selection of the approach, confirmation and correction of the transection plane, choice and use of instruments, and control of bleeding. Mastering liver parenchymal transection techniques can improve the completion rate of surgery, reduce the risk of intraoperative complications, and ensure the precise implementation of laparoscopic liver resection. Currently, there are still many technical challenges in laparoscopic parenchymal transection. It is believed that with the accumulation of experience and innovation in instruments, the techniques for liver parenchymal transection will also develop and become increasingly perfect.

2 Liver parenchyma dissecting-first method versus hepatic pedicle-first approach in laparoscopic right hemihepatolobectomy

XIAO Liang , TAN Sheng , LONG Guo , MI Xingyu , MO Lei , YANG Hanrui , ZHOU Ledu

2024, 33(7):1035-1042. DOI: 10.7659/j.issn.1005-6947.2024.07.002

[Abstract](117) [HTML](81) [PDF 1.35 M](779)

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Background and Aims Laparoscopic right hemihepatectomy (LRH) is a complex minimally invasive liver resection surgery that requires a long learning curve. Traditional LRH procedure adheres to the practice of "pedicle-first and intrathecal dissection" used in open liver resection, which involves first dissociating the right hepatic artery, right portal vein, and right bile duct after removing the gallbladder, then severing them before dividing the liver parenchyma. However, this method is time-consuming and labor-intensive and carries a risk of bleeding if not performed correctly. The authors have developed a technique during prior clinical work that prioritizes liver parenchymal dissection before handling the target hepatic pedicle, named the "liver parenchyma dissecting-first" (LPDF) method. This method does not change the extent of the resection but adjusts the order of the procedure. Preliminary experience suggests that it simplifies the hemihepatectomy process and facilitates the broader application of LRH. This study was peformed to further explore the advantages of LPDF over the pedicle-first method in LRH.Methods Using a prospective study approach, eligible liver cancer patients who underwent LRH in Xiangya Hospital of Central South University from August 2021 to August 2023 were randomly divided into observation group and control group. Patients in the observation group underwent the LPDF method during surgery, while those in the control group used the pedicle-first method. Perioperative clinical variables were collected and compared between the two groups.Results A total of 19 patients were included, with 10 in the observation group and 9 in the control group. There were no statistically significant differences in baseline data between the two groups (all P>0.05). The operative time in the observation group was significantly shorter than that in the control group (224.30 min vs. 267.78 min, P=0.045). Other variables, including intraoperative blood loss and transfusion volume, rate of conversion to open surgery, time to postoperative gas passage, length of hospital stay, liver function on the third postoperative day, and incidence of complications, as well as the recurrence-free survival rate, and overall survival rate, showed no statistically significant differences between the two groups (all P>0.05).Conclusion The application of LPDF in LRH simplifies the pedicle handling process compared to the traditional pedicle-first method, shortens the operative time, does not increase the incidence of postoperative complications, and somewhat reduces the risk of bleeding. Further large-sample studies and promotion are recommended.

3 A case report on laparoscopic anatomical liver segment Ⅶ resection with ICG fluorescence-guided puncture positive staining (with video)

WANG Zheng , YOU Nan , HE Yonggang , AIMAITI·Yasen , ZHENG Lu

2024, 33(7):1043-1050. DOI: 10.7659/j.issn.1005-6947.2024.07.003

[Abstract](128) [HTML](121) [PDF 1.72 M](549)

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Background and Aims Laparoscopic anatomical liver resection has become the main surgical approach for space-occupying lesions located in segment Ⅶ (S7) of the posterior lobe of the liver. However, due to the complex anatomical structure of the S7 hepatic pedicle, there may be ischemic lines on the liver surface, but a lack of effective guidance within the liver parenchyma. Given this, our team adopted indocyanine green (ICG) fluorescence-guided puncture positive staining technique for laparoscopic anatomical liver S7 resection. This paper reports on this technique.Methods The clinical data of one patient who underwent laparoscopic anatomical liver S7 resection using the ICG fluorescence-guided puncture positive staining technique in the Department of Hepatobiliary Surgery, Second Affiliated Hospital of Army Medical University were retrospectively analyzed.Results Following successful preoperative 3D reconstruction simulation to obtain the ICG fluorescent staining region of liver S7, an anatomical liver S7 resection was performed using a caudal approach. During surgery, the liver was transected along the fluorescent boundary and the right hepatic vein, with sequential division of the S7 portal vein (P7) and tributaries of the right hepatic vein from S7. The patient recovered well after surgery, and one month later, an abdominal ultrasound review showed that liver S7 had been resected with no signs of tumor recurrence.Conclusion The ICG fluorescence-guided puncture positive staining technique provides excellent assistance in laparoscopic anatomical liver S7 resection, improving surgical safety and ensuring R₀ resection margins.

4 The application value of intraoperative contrast-enhanced ultrasound in the surgery for malignant liver tumors

YANG Xingguang , CHENG Jianwen , XU Yang , SUN Yunfan , ZHOU Jian , YANG Xinrong

2024, 33(7):1051-1058. DOI: 10.7659/j.issn.1005-6947.2024.07.004

[Abstract](127) [HTML](66) [PDF 1016.77 K](490)

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Background and Aims Currently, Surgical resection is still the main radical approach for malignant liver tumors. However, sometimes due to reasons such as small tumor size, deep location, multiple occurrences, or secondary liver cancer forming "disappearing liver metastases" after drug treatment, it is challenging to accurately locate or detect the tumor during surgery. This study was performed to explore the application value of intraoperative contrast-enhanced ultrasound (CE-IOUS) in the surgery of malignant liver tumors.Methods A retrospective analysis was conducted on 56 patients with malignant liver tumors who were treated and underwent surgical resection at Zhongshan Hospital, Fudan University, from September 2022 to February 2023. The detection rates of liver lesions and the diagnostic accuracy rates for malignant tumors among preoperative enhanced magnetic resonance imaging (P-MRI), preoperative ultrasound (P-US), intraoperative ultrasound (IOUS), and CE-IOUS were compared.Results There were a total of 85 lesions in the 56 patients, among which, P-MRI detected 75 lesions, with postoperative pathology diagnosing 64 malignant lesions and 11 benign lesions, while 10 lesions were missed; P-US detected 46 lesions, with postoperative pathology diagnosing 30 malignant lesions and 16 benign lesions, while 39 lesions were missed; IOUS detected 64 lesions, with postoperative pathology diagnosing 44 malignant lesions and 20 benign lesions, while 21 lesions were missed; CE-IOUS diagnosed 78 lesions as malignant, with postoperative pathology confirming 66 malignant lesions and 12 benign lesions, while 7 lesions were missed. CE-IOUS had a significantly higher lesion detection rate compared to P-US and IOUS (91.8% vs. 54.1%, P<0.001; 91.8% vs. 75.3%, P<0.001) and a higher diagnostic accuracy rate compared to P-US and IOUS (86.8% vs. 65.2%, P<0.001; 86.8% vs. 68.7%, P<0.001). There was no statistically significant difference between CE-IOUS and P-MRI in terms of lesion detection rate, diagnostic accuracy for malignant tumors, and misdiagnosis rate.Conclusion Using Sonazoid contrast agent for CE-IOUS has a higher tumor detection rate and diagnostic accuracy for malignant liver tumors compared to P-US and IOUS. It can be used to identify and locate small lesions that cannot be displayed before surgery, to guide tumor resection or radiofrequency ablation and thereby improve surgical efficacy.

5 Expression of SLC2A1 in hepatocellular carcinoma and its clinical significance

CHEN Yongzhi , BAI Dousheng

2024, 33(7):1059-1069. DOI: 10.7659/j.issn.1005-6947.2024.07.005

[Abstract](112) [HTML](65) [PDF 1.94 M](486)

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Background and Aims The gene solute carrier family 2 member 1 (SLC2A1) encodes the glucose transporter 1 (GLUT1), which is closely related to the glycolysis pathway. Glycolysis is a primary physiological pathway for energy supply in malignant tumors. Therefore, SLC2A1 may be involved in the occurrence and development of various malignant tumors. Given that the expression and biological function of SLC2A1 in hepatocellular carcinoma (HCC) are not fully understood, this study was conducted to investigate the expression and significance of SLC2A1 in HCC through bioinformatics methods and clinical research.Methods The RNA-seq data and clinical information of HCC patients were downloaded from the TCGA database. The expression of SLC2A1 in HCC, its prognostic value, and the differentially expressed genes in HCC patients with different levels of SLC2A1 expression were analyzed through enrichment and correlation analysis. Surgical specimens and clinicopathologic data from 80 HCC patients treated at Northern Jiangsu People's Hospital were collected. The expression of SLC2A1 in HCC and its relationship with clinicopathologic characteristics and prognosis were analyzed. Independent risk factors affecting the prognosis of patients were also screened.Results The analysis of the TCGA database showed that SLC2A1 mRNA was highly expressed in HCC. Patients with high expression had significantly worse overall survival (HR=2.50, 95% CI=1.76-3.56, P<0.001), disease-specific survival (HR=2.13, 95% CI=1.34-3.37, P=0.001), and recurrence-free survival (HR=1.42, 95% CI=1.05-1.93, P=0.025) compared to those with low expression. The expression level of SLC2A1 was closely related to RNA methylation and the degree of immune cell infiltration (all P<0.05). Comparative analysis of clinical pathological data from 80 patients showed that the expression of SLC2A1 protein in HCC tissues was significantly higher than in adjacent non-tumor tissues (P<0.05). SLC2A1 expression level was significantly associated with TNM stage, hepatitis B infection, and vascular invasion (all P<0.05). Univariate analysis showed that TNM stage (HR=1.921, 95% CI=1.365-1.554, P=0.01), vascular invasion (HR=1.925, 95% CI=1.253-2.958, P=0.003), hepatitis B infection (HR=1.365, 95% CI=0.624-1.654, P=0.029), alpha-fetoprotein (HR=1.629, 95% CI=1.063-2.479, P=0.025), and SLC2A1 (HR=1.934, 95% CI=1.261-2.965, P=0.002) were associated with patient prognosis. Multivariate analysis indicated that vascular invasion (HR=1.657, 95% CI=1.036-2.652, P=0.035) and SLC2A1 (HR=1.753, 95% CI=1.132-2.715, P=0.012) were independent risk factors for the prognosis of HCC patients.Conclusion SLC2A1 is highly expressed in HCC, and its high expression is closely related to poor prognosis in patients. Besides its role in glycolysis, SLC2A1 may have various biological functions. Further research on SLC2A1 may potentially identify new targets for the prevention, treatment, and prognostic evaluation of HCC.

6 Efficacy of apatinib combined with camrelizumab in the treatment of advanced hepatocellular carcinoma and its impact on patients' immune function and tumor markers

HUANG Dawei , JIANG Shiyi , LI Jingping , CHANG Yujuan , JIANG Manhong

2024, 33(7):1070-1077. DOI: 10.7659/j.issn.1005-6947.2024.07.006

[Abstract](75) [HTML](42) [PDF 763.26 K](394)

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Background and Aims In recent years, targeted drug therapy has rapidly developed and become an important method for treating advanced hepatocellular carcinoma (HCC). However, the response rate of first-line targeted drug sorafenib in treating HCC is low, and improving clinical protocols for targeted drug therapy in HCC remains a challenging issue. This study was performed to investigate the clinical efficacy of apatinib combined with camrelizumab in treating intermediate to advanced HCC and its impact on patients' immune function and tumor markers.Methods The clinical data of 137 patients with unresectable intermediate to advanced HCC admitted between May and December 2022 were retrospectively analyzed. Among them, 61 patients were treated with oral apatinib alone (targeted group), and 76 received intravenous camrelizumab in addition to oral apatinib (targeted-immune group). The objective response rate (ORR) and disease control rate (DCR) of the two groups were compared; levels of T lymphocyte subsets (CD3⁺, CD4⁺, CD8⁺), alpha-fetoprotein (AFP), Golgi protein 73 (GP-73), and AFP-L3 were measured; liver and kidney function indicators and adverse reactions were monitored. A 12-month follow-up was conducted to assess the two groups' progression-free survival (PFS).Results Before treatment, there were no statistically significant differences in general data, liver and kidney function indicators, and immune and tumor marker levels between the two groups (all P>0.05). After treatment, the ORR and DCR in the targeted-immune group were higher than those in the targeted group (40.79% vs. 16.39%, P=0.02; 60.53% vs. 39.34%, P=0.014). The CD3⁺, CD4⁺, and CD4⁺/CD8⁺ levels in the targeted-immune group were higher, while CD8⁺ levels were lower than those in the targeted group (all P<0.05). AFP, GP-73, and AFP-L3 levels in the targeted-immune group were lower than those in the targeted group (all P<0.05). The total bilirubin and alanine aminotransferase levels in the targeted-immune group were lower than those in the targeted group (both P<0.05). The incidence of skin capillary hemangiomas was higher in the targeted-immune group than in the targeted group (42.11% vs. 18.03%, P<0.05). In contrast, the incidence of other adverse reactions did not differ significantly between the two groups (all P>0.05). After 12 months of follow-up, the median PFS in the targeted-immune group was significantly longer than that in the targeted group (10 months vs. 6 months, χ²=9.954, P<0.05).Conclusion Apatinib combined with camrelizumab in treating HCC can enhance T lymphocyte levels, reduce tumor marker levels, effectively prolong survival time, and have better efficacy than targeted therapy alone, with reasonable safety.

7 Clinical characteristics and prognostic analysis of hepatic angiomyolipoma

CHEN Lun , HE Liuqing , WU Jing , HE Chao

2024, 33(7):1078-1090. DOI: 10.7659/j.issn.1005-6947.2024.07.007

[Abstract](113) [HTML](61) [PDF 2.96 M](1087)

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Background and Aims Hepatic angiomyolipoma (HAML) is a rare benign liver tumor that can be difficult to distinguish from other benign and malignant liver tumors. The clinical diagnosis is challenging, and the treatment strategies and prognosis remain unclear. This study was performed to explore the clinical, imaging, and pathological characteristics, as well as the treatment strategies and prognosis of HAML, to provide a reference for its clinical diagnosis and treatment.Methods The clinical, pathological, imaging, and follow-up data of 46 cases of HAML treated in the Department of Hepatobiliary and Pancreatic Surgery of the Second Xiangya Hospital of Central South University from January 2012 to December 2023 were retrospectively analyzed.Results Among the 46 HAML patients, 12 were male (26.1%) and 34 were female (73.9%), with an age range of 20 to 70 years (median age of 46 years). Twenty-nine cases were asymptomatic at onset, 17 presented with abdominal discomfort, 6 had concurrent hepatitis B, and 7 had concurrent renal angiomyolipoma (RAML). No cases were associated with tuberous sclerosis. Tumor markers (AFP, CEA, CA19-9, and abnormal prothrombin Ⅱ) were not significantly abnormal. Based on clinical data from 4 HAML patients, the average growth rate of HAML was 0.46 cm/year, with a median growth rate of 0.39 cm/year. Imaging characteristics were diverse, with the accuracy rates of preoperative imaging diagnosis of HAML being 3.8% for ultrasound, 34.1% for CT, and 40.9% for MRI. Among the 46 samples, 26 cases (56.5%) had left liver lesions, 18 cases (39.1%) had right liver lesions, and 2 cases (4.3%) had caudate lobe lesions. One case had multiple lesions confined to the left liver, and the remaining 45 cases had single lesions. Tumor diameters ranged from 1 to 15 cm, with a median diameter of 4.3 cm. Pathological results indicated that 41 cases were benign, while 5 cases were malignant; 10 cases were epithelioid HAML. Immunohistochemistry showed 100% positivity for HMB-45 and Melan-A, 95.1% for SMA, 89.7% for CD34, and 54.5% for S-100. Follow-up ranged from 0.25 to 12 years, with 16 cases lost to follow-up. One case recurred 19 months after the operation and 2 years later died of lung adenocarcinoma (confirmed by postoperative pathology at our center), and another case died of lung cancer 5 years after the operation (confirmed by pathology at an external hospital). Both deaths were unrelated to HAML. The remaining 28 patients were healthy with no recurrence or metastasis.Conclusion HAML predominantly occurs in middle-aged women, often without apparent symptoms, and grows slowly, making it prone to misdiagnosis through imaging. Pathological diagnosis is the gold standard for HAML, with HMB-45 and Melan-A positivity being specific indicators. The majority of HAML cases are benign, with a minority being malignant. Overall prognosis is good, but epithelioid and malignant HAML have a risk of recurrence, warranting active follow-up. Surgical resection is an effective treatment for HAML.

8 Effects and mechanisms of regorafenib combined with PD-L1 antibody on liver cancer xenograft in mice

NI Mingli , PAN Wei , XU Qian

2024, 33(7):1091-1099. DOI: 10.7659/j.issn.1005-6947.2024.07.008

[Abstract](81) [HTML](49) [PDF 1.34 M](768)

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Background and Aims Regorafenib treatment for liver cancer inevitably presents side effects and limited efficacy. Programmed death-ligand 1 (PD-L1) monoclonal antibody can effectively block the "tumor immune escape mechanism" and exert significant anti-tumor effects. Therefore, this study was conducted to explore the anti-cancer effect of regorafenib combined with PD-L1 monoclonal antibody in a mouse model of transplanted liver cancer.Methods After establishing a liver cancer transplant model in Balb/C nude mice, the mice were treated with regorafenib (regorafenib group), atezolizumab (PD-L1 antibody group), regorafenib + atezolizumab (combination group), or saline (model group) for 4 weeks. Tumor volumes were dynamically measured in each group during the treatment period. After 4 weeks, the transplanted tumors were excised from the mice, and flow cytometry, TUNEL assay, and HE staining were used to detect CD4⁺ and CD8⁺ cell infiltration, apoptosis rate, and morphological characteristics of the tumor tissues. Additionally, qRT-PCR and Western blot were employed to detect the expression of CD31, vascular endothelial growth factor (VEGF), proliferating cell nuclear antigen (Ki-67), B-cell lymphoma 2 (Bcl-2), and Bax in the tumor tissues.Results There was no statistically significant difference in tumor volumes among the four groups of mice before treatment (P>0.05). At weeks 1, 2, 3, and 4 of treatment, the tumor volumes in each treated group were significantly smaller than those in the model group, and the tumor volume in the combination group was significantly smaller than those in the two monotherapy groups (all P<0.05). However, there was no significant difference in tumor volume between the two monotherapy groups (all P>0.05). The proportion of CD4⁺ and CD8⁺ cells in tumor tissues was significantly higher in each treated group than those in the model group, with the increase being in the order of regorafenib group <PD-L1 antibody group < combination group (all P<0.05). The apoptosis rate of tumor cells was significantly higher in each treated group compared to the model group, with the increase being in the order of regorafenib group <PD-L1 antibody group < combination group (all P<0.05). HE staining showed large, deeply stained, densely arranged nuclei in tumor cells of the model group, while various degrees of nuclear shrinkage, reduced cell numbers, and patchy necrosis were observed in the treated groups, with the most pronounced changes in the combination group. Compared to the model group, the expression levels of CD31, VEGF, Ki-67, and Bcl-2 mRNA and protein in tumor tissues were significantly lower in the treated groups. In contrast, the expression levels of Bax mRNA and protein were significantly higher. The extent of these changes was more pronounced in the combination group than in the two monotherapy groups, with no significant difference between the two monotherapy groups (all P>0.05).Conclusion Regorafenib combined with PD-L1 monoclonal antibody can effectively inhibit the growth of liver cancer, and the intensity is greater than that of either treatment alone. This effect may be achieved through the synergistic interaction of their different mechanisms of action.

9 Effect of sleeve gastrectomy in regulating the GLP-1/DPP-4 pathway to inhibit oxidative stress-induced adipose inflammation in obese mice

MAIMAITI· Yisireyili , YUSUPUJIANG· Yimingjiang , WANG Yongkang , ABABOKELI· Wusiman , AIKEBAIER· Aili , LI Yiliang , KELIMU· Abudureyimu

2024, 33(7):1100-1110. DOI: 10.7659/j.issn.1005-6947.2024.07.009

[Abstract](63) [HTML](54) [PDF 1.52 M](416)

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Background and Aims Sleeve gastrectomy (SG) is an effective method for treating obesity, but the mechanisms through which it exerts its effects are not fully understood. The glucagon-like peptide-1 (GLP-1) and dipeptidyl peptidase-4 (DPP-4) signaling pathways are closely related to the chronic oxidative stress state and adipose inflammation associated with obesity. However, it remains unclear whether the therapeutic effects of SG impact this pathway. Therefore, this study investigates the effects of SG on the GLP-1/DPP-4 pathway, oxidative stress, and inflammatory response in the adipose tissue of high-fat diet-induced obese mice.Methods Thirty mice were fed a high-fat diet to establish an obesity model, while another ten mice fed a standard diet were the normal control group. The 30 obese model mice were randomly divided into three groups to undergo SG operation (model + SG group), and sham operation (model + sham operation group), or to receive no treatment (simple model group), respectively. After surgery, all groups were fed a standard diet for 4 weeks. Visceral fat tissue samples were collected, and pathological changes in adipose tissue were observed using HE staining. Immunohistochemistry and qRT-PCR methods were used to analyze the expression of GLP-1 and its receptor GLP-1R, DPP-4, NADPH oxidase 4 (Nox-4), antioxidant enzymes [manganese superoxide dismutase (MnSOD), glutathione peroxidase (GSH-Px), catalase (CAT)], macrophage surface markers (CD11b), monocyte/macrophage surface markers (CD68, F4/80), and pro-inflammatory factors [monocyte chemoattractant protein-1 (MCP-1), IL-1β, IL-6, TNF-α] in the adipose tissue.Results HE staining showed that all obesity model groups had monocyte infiltration and inflammatory responses in adipose tissue compared to the normal control group. However, these responses were weaker in the model + SG group than those in the simple model group and the model + sham operation group. Immunohistochemistry results showed that the expressions of GLP-1 and GLP-1R were decreased compared to the normal control group. In contrast, DPP-4 expression was increased, and the proportion of CD11b positive cells and Nox-4 expression increased in the adipose tissue of all obesity model groups. However, these changes were significantly weaker in the model + SG group than those in the simple model group and the model + sham operation group, with no significant differences between the latter two groups.qRT-PCR results showed that in all obesity model groups compared to the normal control group, the mRNA expressions of GLP-1 and GLP-1R were decreased, while the mRNA expression of DPP-4 was increased (all P<0.05); the mRNA expression of CD68, F4/80 significantly increased (all P<0.05), the mRNA expression of Nox-4 increased, while the mRNA expression of MnSOD, GSH-Px, and CAT significantly decreased (all P<0.05); MCP-1, IL-1β, IL-6, and TNF-α expression significantly increased (all P<0.05). However, the magnitudes of changes in these variables were significantly smaller in the model + SG group compared to the simple model group and the model+ sham operation group (all P<0.05). At the same time, there were no significant differences in the magnitudes of changes between the latter two groups (all P>0.05).Conclusion SG operation can effectively regulate the GLP-1/DPP-4 pathway in adipose tissue and inhibit the immune responses, oxidative stress, and abnormal expression of pro-inflammatory factors, thereby improving the inflammatory response in adipose tissue.

10 Prognostic factors and construction of prognostic prediction model for simultaneously diagnosed liver and lung metastases from colorectal cancer

ZHU Jiangpeng , LI Guangyao , YAO Yuan , ZHU Weiwei , HUANG Wei

2024, 33(7):1111-1121. DOI: 10.7659/j.issn.1005-6947.2024.07.010

[Abstract](99) [HTML](70) [PDF 1.36 M](444)

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Background and Aims Colorectal cancer (CRC) can metastasize to distant organs, leading to poor prognosis, with liver and lung metastases being the most common. However, simultaneous diagnosed liver and lung metastases from colorectal cancer (SLLMCRC) are rarely reported compared to isolated lung or liver metastases. Therefore, this study was conducted to explore the prognostic factors for patients with SLLMCRC and to develop a prognostic prediction model to provide reference for the selection of treatment plans and evaluation of therapeutic efficacy.Methods Data of patients diagnosed with SLLMCRC from 2010 to 2019 were extracted from the SEER database. After applying inclusion and exclusion criteria, 800 eligible patients were selected. These were randomly divided into a modeling cohort (560 cases) and a validation cohort (240 cases) in a 7∶3 ratio. The Cox proportional hazards regression model was used to identify independent risk factors for overall survival (OS) of SLLMCRC patients, while the Fine-Gray competitive risk model was employed to identify independent risk factors for cancer-specific survival (CSS). Prognostic nomograms for predicting OS and CSS were constructed based on these independent risk factors. The reliability of the models was validated using the consistency index, ROC curve, and calibration curve.Results There were no statistically significant differences in baseline factors between the modeling and validation cohorts (all P>0.05). Age (50-69 years: HR=1.39, 95% CI=1.07-1.81; ≥70 years: HR=1.94, 95% CI=1.46-2.58), primary tumor resection (HR=0.67, 95% CI=0.48-0.95), CEA level (HR=1.39, 95% CI=1.04-1.87), and chemotherapy (HR=0.22, 95% CI=0.18-0.28) were independent factors affecting SLLMCRC patients OS (all P<0.05). The older age of SLLMCRC patients, the lower the OS rate, while having primary tumor resection, negative CEA result, and receiving chemotherapy result in higher OS rate. Age between 50-69 years (HR=1.05, 95% CI=1.01-1.12), number of regional lymph nodes removed (HR=0.67, 95% CI=0.48-0.90), and chemotherapy (HR=0.45, 95% CI=0.34-0.61) were independent factors affecting CSS (all P<0.05). Older age correlated with lower CSS rate, while more extensive regional lymph node removal and receiving chemotherapy correlated with higher CSS rate. The nomogram validation showed that the 1, 2, and 3-year OS ROC values for the modeling cohort were 0.643, 0.587, and 0.591, respectively; for the validation cohort, these values were 0.631, 0.623, and 0.628. The 1, 2, and 3-year CSS ROC values for the modeling cohort were 0.607, 0.610, and 0.681, respectively; for the validation cohort, these values were 0.624, 0.618, and 0.624. The calibration curves for OS and CSS were relatively close to the ideal 45° reference line.Conclusion Age, primary tumor resection, CEA level, number of regional lymph nodes removed, and chemotherapy are closely related to the prognosis of patients with SLLMCRC. Radiotherapy may not benefit SLLMCRC patients. The constructed prediction model has high accuracy and reliability, providing evidence to support clinical decision-making and evaluation of treatment efficacy for clinicians.

11 Construction of a prediction model for severe postoperative complications after pancreatoduodenectomy based on sarcopenia combined with POSSUM score

A Rula , LU Jianhui , XIA Yijun , QIN Shana , JIA Guangpeng , HU Zhiwei

2024, 33(7):1122-1132. DOI: 10.7659/j.issn.1005-6947.2024.07.011

[Abstract](68) [HTML](37) [PDF 983.39 K](426)

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Background and Aims Pancreatoduodenectomy (PD) is a classic surgical method for treating malignant tumors at the pancreatoduodenal junction and other related diseases. Despite advancements in surgical techniques, the incidence of severe postoperative complications remains high. These complications not only affect the patient's recovery process but also pose life-threatening risks. Therefore, predicting the risk of severe complications after PD is crucial for developing targeted prevention and treatment strategies. Recently, sarcopenia, a condition associated with an increased risk of various postoperative complications, has garnered significant attention. The POSSUM scoring system, widely used for surgical risk assessment, has shown preliminary validation in its predictive efficacy. This study was conducted to identify risk factors for severe complications following PD and to develop a risk prediction model based on sarcopenia combined with POSSUM score to improve the accuracy of predicting severe postoperative complications and provide a scientific basis for clinical decision-making.Methods The clinical data of 79 patients who underwent PD from 2016 to 2023 were retrospectively analyzed. The skeletal muscle index at the third lumbar vertebra was obtained using Slice Omatic software, and sarcopenia was diagnosed based on this index. Postoperative complications were recorded and graded according to the Clavien-Dindo classification, categorizing them into severe complications (≥Ⅲa) and non-severe complications (<Ⅲa). The POSSUM scoring system was used to assess surgical risk, and the receiver operating characteristic (ROC) curve was plotted to evaluate the predictive efficacy of the POSSUM score for severe complications after PD, with the optimal cutoff point determined by the Youden index. Univariate and binary multivariate Logistic regression analyses were conducted to identify independent risk factors for severe postoperative complications. Subsequently, a nomogram risk prediction model was constructed using R language, and its predictive efficacy was comprehensively evaluated using the ROC curve, calibration curve, the Hosmer-Lemeshow goodness-of-fit test, and internal validation of the concordance index.Results Among the 79 patients, 41 had sarcopenia, and 38 did not. The incidence of severe postoperative complications was 27.85%. Significant differences were found between the severe and non-severe complication groups regarding age, sarcopenia, POSSUM score, intraoperative blood loss, preoperative white blood cell count, and preoperative neutrophil count (all P<0.05). Binary Logistic regression analysis showed that sarcopenia, POSSUM score, and intraoperative blood loss were independent risk factors for severe postoperative complications after PD (all P<0.05). The risk prediction model constructed based on these risk factors had an area under the ROC curve (AUC) of 0.895 9. The calibration curve of the prediction model was close to the ideal curve, indicating good predictive accuracy. The Hosmer-Lemeshow goodness-of-fit test also suggested a good fit for the prediction model, and internal validation of the concordance index confirmed the nomogram model's good predictive ability.Conclusion Sarcopenia, POSSUM score, and intraoperative blood loss are independent risk factors for severe postoperative complications after PD. The risk prediction model based on sarcopenia combined with the POSSUM score has high predictive efficacy, providing clinicians with a more accurate risk assessment tool and can help develop individualized prevention and treatment strategies to reduce the incidence of severe postoperative complications following PD.

12 Impact of surgical treatment on the prognosis of gastric squamous cell carcinoma patients: a propensity score matching analysis based on the SEER database

CHEN Xinming , ZHAO Pingwu , TANG Hong , HE Yunsheng , PENG Xuanfu , HUANG Kun , ZHAO Pan , LIU Yang

2024, 33(7):1133-1141. DOI: 10.7659/j.issn.1005-6947.2024.07.012

[Abstract](67) [HTML](88) [PDF 977.99 K](413)

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Background and Aims Gastric squamous cell carcinoma (GSCC) is a rare malignant tumor of the stomach. There is a lack of large-scale clinical data studies on this patient population, and the prognostic value of surgical treatment remains unclear. Therefore, this study was conducted to investigate the impact of surgical treatment on the prognosis of GSCC patients.Methods The clinical data of GSCC patients pathologically diagnosed between 2000 and 2019 were extracted from the SEER database. The impact of surgical treatment on the overall survival (OS) and cancer-specific survival (CSS) of GSCC patients were analyzed, and the influencing factors for OS and CSS, as well as the value of surgical treatment for GSCC patients with different clinicopathologic characteristics, were determined.Results A total of 334 GSCC patients were included, among whom 83 (24.85%) underwent surgical treatment, while 251 (75.15%) did not. After 1:1 propensity score matching to balance baseline data, each group consisted of 81 patients. Survival analysis showed that the 5-year OS rate (32.07% vs. 11.08%, χ²=20.30, P<0.001) and CSS rate (41.93% vs. 18.45%, χ²=17.10, P<0.001) in the surgery group were significantly better than those in the non-surgery group. Cox multivariate analysis indicated that marital status, pathological differentiation, SEER stage, surgical treatment, and radiotherapy were independent factors for OS and CSS in GSCC patients (all P<0.05). Further stratified analysis based on clinicopathologic characteristics showed that the OS was significantly improved in those married (HR=0.42, 95% CI=0.251-0.70, P=0.001), with highly differentiated tumor (HR=0.09, 95% CI =0.01-0.84, P=0.035), with localized tumor (HR=0.33, 95% CI=0.17-0.65, P=0.001), and receiving radiotherapy (HR=0.35, 95% CI=0.21-0.58, P<0.001) who underwent surgery. Similarly, CSS was significantly improved in those married (HR=0.44, 95% CI=0.25-0.78, P=0.005), with highly differentiated tumor (HR=0.09, 95% CI=0.01-0.84, P=0.035), with localized tumor (HR=0.34, 95% CI=0.15-0.75, P=0.007), and receiving radiotherapy (HR=0.31, 95% CI=0.18-0.55, P<0.001) who underwent surgery.Conclusion Surgical treatment can effectively improve the prognosis of GSCC patients. Particularly, those who are married, have highly differentiated tumors and localized tumors, and receive radiotherapy are the best beneficiaries of surgical treatment.

13 Meta-analysis of the impact of visceral fat area on the efficacy, postoperative complications, and patients' prognosis of radical gastrectomy

MA Yuqi , BI Xinran , ZHANG Wentao , GONG Shiyi , WAN Haohao , MA Liang , FAN Wanqi , DENG Yuan , HU Ming , MA Yuntao

2024, 33(7):1142-1152. DOI: 10.7659/j.issn.1005-6947.2024.07.013

[Abstract](163) [HTML](41) [PDF 1019.05 K](523)

Abstract:
Background and Aims Visceral obesity is not only a risk factor for various cancers but also closely related to surgical outcomes and the occurrence of postoperative complications. Although there are numerous studies on the impact of visceral fat area (VFA) on the efficacy and postoperative complications of radical gastrectomy as well as postoperative survival of patients, there is still a lack of comparative analysis with large sample sizes. Therefore, this study was performed to explore the relationship between VFA defined by CT at the third lumbar vertebra level (L3-CT) and the efficacy, postoperative complications, and prognosis of radical gastrectomy through a Meta-analysis.Methods A comprehensive search was conducted across multiple domestic and international databases to collect clinical studies comparing the postoperative outcomes of gastric cancer patients with different VFAs (all calculated by L3-CT). The search period was from the inception of the database to July 2023. After literature screening according to inclusion and exclusion criteria, data extraction, Meta-analysis was performed using RevMan 5.3 software.Results A total of 9 studies meeting the criteria were included, with 6 retrospective cohort studies and 3 prospective studies, comprising a total sample size of 4 521 cases. The NOS scores of the included studies ranged from 7 to 9. Meta-analysis results showed that the high VFA group had longer operative time (MD=19.59, 95% CI=0.93-38.25, P=0.04), greater blood loss (MD=60.79, 95% CI=10.20-111.38, P=0.02), and fewer lymph nodes dissected (MD=-4.85, 95% CI=-6.11--3.60, P<0.000 01). The high VFA group also had prolonged postoperative hospital stay (MD=1.75, 95% CI=0.99-2.51, P<0.000 01). VFA was associated with the overall incidence of complications (OR=1.57, 95% CI=1.32-1.87, P<0.000 01), with the high VFA group more likely to develop pancreatic fistula (OR=2.58, 95% CI=1.41-4.69, P=0.002) and anastomotic leakage (OR=1.77, 95% CI=1.12-2.79, P=0.01). There was no statistically significant difference in the 5-year survival rate between the different VFA groups (OR=1.17, 95% CI=0.92-1.49, P=0.21).Conclusions High VFA prolongs operative time, with increased intraoperative blood loss, reduced the number of lymph nodes dissected, and makes patients more prone to pancreatic fistula and anastomotic leakage. Due to the limitations in the number and quality of studies, these conclusions require further validation through higher quality studies.

14 Research progress of standardized laparoscopic segmentectomy based on Laennec's capsule theory

LIN Dexin , CHANG Guijian , ZHUO Xinbin , LEI Wendi , ZHANG Yong , LI Xuan

2024, 33(7):1153-1161. DOI: 10.7659/j.issn.1005-6947.2024.07.014

[Abstract](87) [HTML](46) [PDF 1.29 M](432)

Abstract:
With the rapid development of laparoscopic liver surgery, laparoscopic hepatectomy has gradually become a mainstream procedure in liver surgery, and the anatomical understanding of the liver membrane plays a crucial role in this. The Laennec's capsule encapsulates the entire liver. It enters the liver parenchyma along with the Glisson's capsule and hepatic veins, separating the liver parenchyma from the Glisson's capsule, "six portal triads" system, hepatic veins, and the retrohepatic inferior vena cava. It is the standard intermembrane space for safe dissection and location of the hepatic pedicle during hepatectomy. Accurate liver tissue resection can be achieved by separating the Glisson's capsule that enters the liver and the hepatic veins that exit the liver through the Laennec's capsule. Currently, there is a scarcity of literature strictly adhering to the standard laparoscopic liver segmentectomy, and even fewer studies report on laparoscopic liver segmentectomy combined with Laennec's membrane anatomy. Histology has confirmed the existence of the Laennec's membrane, which is independent and not continuous with the Glisson's capsule at the hepatic hilum; there is a space between them that deepens into the liver parenchyma along with the Glisson's capsule. Utilizing the space between the Glisson's capsule at the hepatic hilum and the Laennec's capsule to separate and ligate the Glisson's capsule of each liver segment provides the anatomical basis for standardized liver segmentectomy. This paper summarizes relevant research on the theory of Laennec's capsule, combined with clinical exploration reports on laparoscopic segmental hepatectomy, to provide a reference for standardized laparoscopic liver segmentectomy based on Laennec's capsule.

15 Arterial perfusion chemotherapy combined with systemic drugs in the treatment of intermediate and advanced hepatocellular carcinoma: applications and considerations

JIANG Shusen , TAN Lijun , LI Shungang , YAO Hongbing

2024, 33(7):1162-1171. DOI: 10.7659/j.issn.1005-6947.2024.07.015

[Abstract](77) [HTML](58) [PDF 756.75 K](420)

Abstract:
The field of treatment for advanced hepatocellular carcinoma (HCC) is witnessing a cutting-edge exploration aimed at surpassing traditional boundaries and leading medicine towards more precise and personalized directions. The introduction of molecular targeted therapy has injected new vitality into this field, revolutionizing treatment strategies by acting on specific sites of tumor cells, successfully improving patients' quality of life. Amidst this wave of transformation, hepatic arterial infusion chemotherapy (HAIC) has gained significant attention as an important local treatment approach. Its combined application with targeted drugs is expected to achieve synergistic effects, bringing more significant therapeutic outcomes for patients with advanced HCC. HAIC combined with sorafenib has shown significant potential in improving survival rates for patients with advanced HCC, particularly for those with portal vein invasion. However, the accompanying adverse events are challenges that cannot be ignored. Similarly, HAIC combined with lenvatinib has also shown good survival benefits and tolerability of adverse reactions in the treatment of advanced HCC, but related clinical studies are still insufficient. Overall, the clinical efficacy and safety of HAIC combined with targeted drug therapy require more high-quality evidence to support. Meanwhile, the rise of immunotherapy has become one of the focal points in the current treatment field, offering new hope for the treatment of advanced HCC by overcoming tumor immune tolerance through activating the body's immune response. HAIC combined with immune inhibitors has demonstrated superior efficacy in the treatment of advanced HCC and holds a significant position in HCC conversion therapy. Moreover, HAIC combined with targeted therapy not only shows remarkable advantages in tumor reduction and surgical conversion rates but is also unanimously recommended by domestic experts as an important treatment method for HCC patients with portal vein tumor thrombus. Despite this, HAIC combined therapy still faces a series of challenges, including how to select the dominant population, grasp the timing of treatment, determine the best treatment plan, and manage adverse reactions, which still need further exploration. Therefore, this paper aims to elaborate on the research progress of HAIC combined with systemic drugs for intermediate to advanced HCC, in order to provide useful references for the optimization of treatment plans.

16 Cuproptosis in the pathogenesis of hepatocellular carcinoma: a research progress review

DONG Changjun , ZHANG Xianlin

2024, 33(7):1172-1179. DOI: 10.7659/j.issn.1005-6947.2024.07.016

[Abstract](129) [HTML](34) [PDF 706.59 K](394)

Abstract:
Copper is one of the essential trace elements for living organisms. Both copper deficiency and overload can damage cells, and maintaining intracellular copper levels within a reasonable range is crucial. Cuproptosis is a newly established distinct form of programmed cell death. It is primarily characterized by mitochondrial dysfunction. Copper overload in cells can lead to abnormal oligomerization of acylated proteins in the tricarboxylic acid cycle and loss of Fe-S cluster proteins, causing proteotoxic stress responses that disrupt intracellular homeostasis, triggering cuproptosis. One of the conditions for cuproptosis is the higher concentration of copper in hepatocellular carcinoma (HCC) cells compared to normal cells. Cuproptosis plays a crucial role in the development and progression of HCC, contributing significantly to angiogenesis promotion, immune evasion, regulation of classical signaling pathways, and induction of other cell death modalities. Cuproptosis impacts cellular homeostasis and participates in regulating various biological processes. In the immune microenvironment of HCC, bioinformatics analysis has revealed a correlation between cuproptosis and the infiltration of immune cells such as CD8⁺ T cells, follicular dendritic cells, and helper T cells. Its molecular regulatory mechanisms hold the potential to overcome drug resistance, including resistance to anti-PD-L1 therapy and sorafenib. Copper ion carriers like disulfiram can activate other cell death programs, enhancing the sensitivity of HCC treatment and overcoming drug resistance. The anti-tumor strategy of combining copper nanoparticles with copper ion carriers shows promising prospects. Establishing HCC prognostic models based on cuproptosis-related genes offers advantages, but further mechanistic studies and clinical validation are required. In summary, this paper reviews and discusses the key advances and focal points of cuproptosis in the pathogenesis of HCC, aiming to provide a reference for related research.

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Volume 33,Issue 7,2024 Table of Contents

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