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25 March 2024, Volume 29 Issue 02 Previous Issue   
Editorial
Systemic therapy alters the landscape of surgery in hepatocellular carcinoma: opportunities and challenges
SHAO Weiqing, LU Lu, QIN Lunxiu
2024, 29 (02):  93-98.  DOI: 10.16139/j.1007-9610.2024.02.01
Abstract ( 56 )   HTML ( 1 )   PDF (926KB) ( 16 )  

Surgery is still the first choice for patients with hepatocellular carcinoma(HCC). However, about 70% of HCC patients in China are first diagnosed in the advanced stage and have lost the opportunity for surgery. Recently, the rapid development of systematic therapy has brought new hope for patients with advanced HCC. The combination of molecular targeted therapy and immunotherapy with or without local therapy significantly improves the survival of advanced HCC and alters the landscape of surgical treatment in advanced HCC. In addition, systemic therapy also brings new opportunities for perioperative treatment of HCC patients. Conversion therapy, neoadjuvant therapy, and postoperative adjuvant therapy can increase the chances of surgical treatment, reduce the risk of postoperative metastasis and recurrence, and prolong the overall survival of HCC patients. Systematic therapy based on molecular targeted therapy and immunotherapy has been applied through the whole process of HCC surgical treatment, and has completely altered the surgery paradigm of HCC. However, further research is needed to determine the optimal combination protocol, screen the sensitive populations, address drug resistance, and reduce systemic adverse events.

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Consensus and guideline
Interpretation of NCCN clinical practice guidelines for hepatocellular carcinoma, version 2.2023
SHI Chunchao, WANG Kui
2024, 29 (02):  99-105.  DOI: 10.16139/j.1007-9610.2024.02.02
Abstract ( 71 )   HTML ( 0 )   PDF (948KB) ( 28 )  

The National Comprehensive Cancer Network (NCCN), as the world's leading non-profit consortium in the field of oncology, continues to update clinical practice guidelines for multiple malignancies annually and has become a benchmark for clinical practice guidelines in oncology worldwide. Currently, the NCCN clinical practice guidelines for hepatocellular carcinoma have been updated to version 2.2023, as compared with version 1.2023 of its main updates for the content of the discussion section. The NCCN guidelines for hepatobiliary cancers have been reorganized to separate guidelines for biliary tract cancers and hepatocellular carcinoma since version 1.2023. The main updates focus on tumor screening, diagnosis, surgery, adjuvant therapy, locoregional therapy, systemic therapy, and so on. The molecular testing was added for the first time. Therefore, the updates of version 1.2023 were highlighted again in the new version 2.2023. This article interpreted the new guidelines and focused on the aspects of updates.

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Experts forum
Conversion therapy of hepatocellular carcinoma: some pivotal issues to be resolved
ZHAO Lei, ZHONG Jingtao, SUN Huichuan
2024, 29 (02):  106-113.  DOI: 10.16139/j.1007-9610.2024.02.03
Abstract ( 23 )   HTML ( 1 )   PDF (1071KB) ( 6 )  

Progress in the systemic therapies, represented by the molecular target therapies and immune checkpoint inhibitors (ICIs), have significantly improved the prognosis of unresectable hepatocellular carcinoma (uHCC), but long term survial remains limitted. As one of the major combination of systemic and surgical therapies, conversion therapy provides potentially curative opportunity to some uHCC patients. It is widely reported from different domestic centers.The first Chinese expert consensus about it was released in 2021. Yet at the same time, there are many key issues in the practice and theory remains to be resolved. Actively thinking, exploring and finally resolving these issues are essential for establishing and promoting the standardized theoretical system of uHCC conversion therapy.

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Recent advances in subtyping of biliary tract carcinoma
LIN Zhiwen, LIU Hongzhi, ZENG Yongyi
2024, 29 (02):  114-120.  DOI: 10.16139/j.1007-9610.2024.02.04
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Biliary tract carcinoma exhibits high heterogeneity at the genomic, epigenetic, and molecular expression levels. The patients even with the same pathological morphology and clinical stage of biliary tract malignant tumors have substantial differences in the treatment response and prognosis. Traditional pathological histology and clinical classifications are no longer sufficient to meet the demands of the precision medicine era. Molecular subtyping has the potential to provide more personalized cancer treatment strategies. It not only helps to reveal the mechanisms of tumor development and accurately predict disease prognosis, but also plays a crucial role in guiding the development of novel targeted drugs and implementing targeted therapies for specific tumors. With the ongoing development of precision medicine, the role of molecular subtyping in cancer diagnosis, treatment option, and prognosis assessment is increasingly prominent. This paper systematically reviewed the recent progress in the molecular subtyping of biliary tract malignant tumors based on domestic and international clinical and basic research.

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Development and prospect of laparoscopic living donor hepatectomy
LI Shule, LU Lu
2024, 29 (02):  121-125.  DOI: 10.16139/j.1007-9610.2024.02.05
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In recent years, benifit by the advancement of minimally invasive surgical techniques, laparoscopic living donor hepatectomy(LLDH) has experienced rapid development. Since this technology was first reported in 2002, major transplant centers have been continuously developing and accumulating experience. Compared with traditional open surgery, LLDH has advantages such as less trauma, less intraoperative bleeding, and lower incidence of postoperative complications. However, at the same time, there were certain difficulties in managing, such as, warm ischemia time, overcoming learning curves, avoiding biliary complications, and controlling bleeding, still needed to be solved. The application of some new technologies and surgical methods also made this technology more efficient and safer. This article discussed the development history, surgical difficulties and complications, and technical improvements of LLDH, and looked forward to the future prospects and development directions of this technology.

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The role of liver microenvironment cells in colorectal cancer liver metastasis
ZHAO Yiming, WU Zong, WANG Lu
2024, 29 (02):  126-131.  DOI: 10.16139/j.1007-9610.2024.02.06
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The liver is the most common site of metastasis in patients with colorectal cancer(CRC). The liver microenvironment is a diverse assemblage of cells, which has their own unique biological characteristics and functions, supplemented by the interaction between cells, which jointly regulate the tumor microenvironment and play significant role in the occurrence and development of CRC liver metastasis. Consequently, a thorough investigation of the molecular mechanisms underlying CRC liver metastasis is imperative for comprehension of tumor progression, prediction of metastasis risk, and the development of innovative therapeutic strategy. This paper delved into the cellular constituents of the liver tumor microenvironment, elucidating the roles and influences of diverse cell types in the process of CRC liver metastasis, offering fresh insights and strategies for the diagnosis and management of CRC liver metastasis.

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Lecture
Clinical significance of combination of anti-angiogenesis, immune checkpoint inhibitors and chemotherapy in the neoadjuvant treatment of locally advanced gastric cancer
ZHU Zhenggang
2024, 29 (02):  132-137.  DOI: 10.16139/j.1007-9610.2024.02.07
Abstract ( 43 )   HTML ( 0 )   PDF (937KB) ( 7 )  

The combination of anti-angiogenesis, immune checkpoint inhibitors(ICIs) and chemotherapy(target-immune-chemo) has achieved initial results in the comprehensive treatment of gastric cancer. Experimental studies have shown that among various determinants of tumor immunotherapy, tumor microenvironment (TME) plays a crucial role in affecting ICIs efficacy. The biological mechanism leading to immunosuppressive TME is multi-factorial and very complex, but one of clear and important mechanisms is the influence of abnormal neoangiogenesis in tumors. The use of low-dose targeted tumor angiogenesis drugs (such as anti-VEGF /VEGFR monoclonal antibody, etc.) is expected to make tumor vessels normalization and reverse immunosuppressive TME to immunesupportive TME, so as to play synergistic, complementary, anti-tumor effects with ICIs and chemotherapy drugs. Perioperative treatment of locally advanced gastric cancer (LAGC) has become an indispensable and important strategy in surgical comprehensive treatment of gastric cancer. In recent years, a therapeutic combination regimen of anti-angiogenesis, ICIs and chemotherapy (target-immune-chemo) has been clinically applied in the perioperative treatment of LAGC, and the preliminary efficacy [pathologic complete response(pCR), major pathological response(MPR), tumor regression grade(TRG) and treatment-related adverse events(TRAEs), etc.] has shown encouraging results. This article reviewed the relevant clinical research results and made a summary and analysis.

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Original article
Research on the management of the Glissonean pedicle in laparoscopic anatomical hemihepatectomy and the influence of indocyanine green dose on the fluorescence staining effect
LU Zhiyu, SUN Ji, DU Jialu, MENG Xuan, LUO Man, LIU Yue, WANG Hongguang
2024, 29 (02):  138-142.  DOI: 10.16139/j.1007-9610.2024.02.08
Abstract ( 28 )   HTML ( 0 )   PDF (5474KB) ( 5 )  

Objective To investigate the technique and dosage selection of indocyanine green(ICG) fluorescence staining in laparoscopic anatomical hemihepatectomy. Methods A retrospective cross-sectional study was conducted. The clinical date of the patients who underwent laparoscopic anatomical hemihepatectomy in the Cancer Hospital of the Chinese Academy of Medical Sciences from October 2020 to October 2023 was collected and analyzed, and the management of the Glissonean pedicle, the method and effect of ICG fluorescence staining during the operation, the dose of ICG injection, and the postoperative recovery were analyzed. Results A total of 91 laparoscopic anatomical hemihepatectomies were enrolled in this study, including 28 right hemihepatectomies and 63 left hemihepatectomies. The Glissonean pedicle was dissected intra-sheath in 9 cases and extra-sheath in 82 cases. ICG fluorescence staining was all performed using the negative staining method, of which 69 cases(75.8%) were successfully stained. The success rate of staining in the extra-sheath dissection and low-dose ICG group was higher than that in the intra-sheath dissection and high-dose ICG group. The average operation time was (168.5±32.2) minutes, the intraoperative bleeding volume was (152.4±56.3) ml, and the intraoperative blood transfusion rate was 6.6% (6/91), the average postoperative hospital stay was (8.5±2.6) days. One case was converted to laparotomy due to exophytic growth of the tumor compressing the Glissonean pedicle. Four cases had Clavien-Dindo Ⅰ-Ⅱ complications, all of which improved after treatment. There were 3 cases of grade Ⅲa complications, all of which were caused by bile leakage and abdominal cavity infection. They were cured by puncture and drainage. And there were no serious complications above grade Ⅲb. Conclusions In laparoscopic anatomical hemihepatectomy, the ICG fluorescence staining method was recommended to use the negative staining method of the extra-sheath dissection of the Glissonean pedicle, and a lower dose of ICG could help to increase the success rate of fluorescence staining.

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Effect of hyperlipidemia on prognosis of the patients with hepatitis B related hepatocellular carcinoma
SONG Qingjie, TANG Juanjuan, ZHAO Jianquan, SONG hui, YANG Jun
2024, 29 (02):  143-147.  DOI: 10.16139/j.1007-9610.2024.02.09
Abstract ( 15 )   HTML ( 0 )   PDF (1049KB) ( 5 )  

Objective To explore the effect of hyperlipidemia and lipid-lowering therapy on the prognosis of postoperative patients with hepatitis B related hepatocellular carcinoma. Methods The clinical data of the patients with hepatitis B related hepatocellular carcinoma who were operated in our hospital from January 2012 to January 2021 were retrospectively collected. The effect of blood lipid level and related lipid-lowering therapy on the prognosis of postoperative patients with hepatitis B related hepatocellular carcinoma was analyzed. Results Among 166 patients with hepatitis B related hepatocellular carcinoma, there were 63 cases had hyperlipidemia, of which 33 cases were treated by statins. The median postoperative disease free survival time in the hyperlipidemia group was significantly lower than that in the normal blood lipid group (24.8 months vs. 38.5 months, P<0.05), and the median overall survival time in the hyperlipidemia group was also significantly lower than that in the normal blood lipid group (30.1 months vs. 44.5 months, P<0.05). There was no statistically significant difference in prognosis between the patients with hyperlipidemia who used statins or not. The median disease free survival time was 23.4 months vs. 26.3 months, and the median overall survival time was 29.7 months vs. 30.3 months. Conclusions Hyperlipidemia is a risk factor for disease free survival and overall survival after surgery in the patients with hepatitis B related hepatocellular carcinoma. The use of statins alone in hyperlipidemia patients cannot reduce the risk of recurrence and prolong survival time.

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Consistency analysis of mismatch repair protein expression and microsatellite stability in colorectal cancer
ZHU Hui, CAI Jidong, LI Minghan, YANG Wentao, XU Ye
2024, 29 (02):  148-155.  DOI: 10.16139/j.1007-9610.2024.02.10
Abstract ( 30 )   HTML ( 0 )   PDF (996KB) ( 15 )  

Objective To investigate the consistency between mismatch repair proyeins expressions detected by immunohistochemistry (IHC) and microsatellite instability(MSI) identified by next-generation sequencing (NGS), and evaluate the correlation of these results with the clinical characteristics of Chinese colorectal cancer (CRC). Methods Using IHC and NGS to identify mismatch repair (MMR) and MSI status in CRC, and assessing the consistency between these different detection methods. Results The concordance rate of MSI status detected by IHC and NGS was 98.36%, indicating good agreement (Kappa=0.856). Certain pathogenic or likely pathogenic germline variants were present in the pMMR/MSI-H subtype. The co-deficiency of MLH1 and PMS2 was most common in the dMMR/MSS subtype. Patients with inconsistent typing were more likely to have early-onset right-sided colon cancer (P<0.01) and the tumor with relatively poor differentiation. Conclusions The consistency of MSI status detected by IHC and NGS is very high, 98% or more. To avoid the misdiagnosis of MSI status affecting clinical decision-making for treatment plans, it is imperative to ensure the accuracy of MSI analysis, particularly in poorly differentiated early-stage right-sided colon cancers.

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Application of ultrasonic measurement in evaluating difficult laryngoscopy exposure of OSAHS patients
LI Yuanyuan, JIN Chenyu, FANG Shudong, ZHI Yankang
2024, 29 (02):  156-160.  DOI: 10.16139/j.1007-9610.2024.02.11
Abstract ( 14 )   HTML ( 0 )   PDF (887KB) ( 3 )  

Objective To explore the feasibility of ultrasonic measurement of the skin to hyoid bone distance, skin to epiglottis distance and skin to anterior commissure of vocal cords distance for predicting difficult laryngoscopy exposure in obstructive sleep apnea hypopnea syndrome(OSAHS) patients. Methods One hundred and fifty OSAHS patients with ASA Ⅰ-Ⅲ level, who underwent elective uvulopalatopharyngoplasty(UPPP) surgery under general anesthesia,were analyzed. Rountine airway assessment (Mallampati classification) and ultrasound measurement of the skin to hyoid bone distance, skin to epiglottis distance and skin to anterior commissure of vocal cords distance were performed before anesthesia. Intubation under direct laryngoscopy and the classification of laryngoscopy exposure was recorded. Cormack-Lehane classification Ⅲ-Ⅳ grade was defined as difficult laryngoscopy exposure. According to the classification results, patients were divided into two groups: non-difficult laryngoscopy exposure group and difficult laryngoscopy exposure group. We analyzed and compared the Malampati grading and ultrasound measurements between two groups. The receiver operating characteristic(ROC) curve and the optimal cut-off point of ultrasonic measurements were calculated. The effects of different methods for predicting difficult laryngoscopy exposure were analyzed. Results The proportion of cases whose Mallampati airway classification grade>Ⅱ in difficult laryngoscopy exposure group was significantly more than that in non-difficult laryngoscopy exposure group (P<0.05).The skin to hyoid bone distance and skin to epiglottis distance in difficult laryngoscopy exposure group were significantly longer than those in non-difficult laryngoscopy exposure group (P<0.05). The optimal cut-off point of the skin to hyoid bone distance and skin to epiglottis distance were 1.12 cm and 2.23 cm respectively. There was no significant difference in the skin to anterior commissure of vocal cords distance between two groups. Conclusion Ultrasound measurement of the skin to hyoid bone distance and skin to epiglottis distance had a good predictive value in difficult laryngoscopy exposure of the OSAHS patients.

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Role and possible mechanism of pseudogene FMO6P in inhibiting invasion and metastasis of gastric cancer
WU Xiongyan, LI Zhen, YU Zhenjia, SU liping
2024, 29 (02):  161-169.  DOI: 10.16139/j.1007-9610.2024.02.12
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Objective To determine the expression and clinical significance of pseudogene FMO6P in gastric cancer, and explore its functions and underlying molecular mechanism in regulating the invasion and metastasis of gastric cancer cells. Methods The expression level of FMO6P in gastric cancer tissues and cell lines was detected by quantitative real time polymerase chain reaction(qRT-PCR). The migration and invasion abilities of gastric cancer cells were detected by transwell assay. The effect of FMO6P on the tumor formation and peritoneal dissemination of gastric cancer cells were evaluated by injecting FMO6P-overexpressing gastric cancer cells into the subcutaneous or peritoneal cavity of nude mice respectively. The expression levels of epithelial-mesenchymal transition(EMT) markers, including E-cadherin, N-cadherin, ZEB1, MMP2, and the activation of AKT/mTOR pathway in FMO6P-overexpressing or knockdown gastric cancer cells were measured by Western blot. Results The expression of FMO6P was significantly reduced in tumor tissues compared to its adjacent non-tumor tissues of gastric cancer, FMO6P expression level in tumor tissues was correlated with tumor size and TNM stage. Overexpression of FMO6P significantly inhibited the invasion and migration abilities of gastric cancer cells, while downregulation of FMO6P expression promoted the invasion and migration ability of gastric cancer cells. Overexpression of FMO6P in gastric cancer cells significantly inhibited the subcutaneous tumor formation and peritoneal dissemination of gastric cancer cells in nude mice. Moreover, overexpression of FMO6P promoted the expression of E-cadherin, and inhibited the expression of N-cadherin, ZEB1, and MMP2 in gastric cancer cells. The phosphorylation levels of AKT and mTOR were also downregulated in gastric cancer cells overexpressing FMO6P. Conclusion All these findings suggested that pseudogene FMO6P suppresses the invasion and migration potential of gastric cancer cells in vitro and in vivo, which is possibly through the inhibition of the AKT/mTOR signaling pathway.

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Screening and identification of the beneficiaries of adjuvant chemotherapy based on the prognostic model of intrahepatic cholangiocarcinoma
LIN Qizhu, LIU Hongzhi, HUANG Tingfeng, FAN Ruilin, ZHOU Weiping, ZHENG Shuguo, LOU Jianying, ZENG Yongyi
2024, 29 (02):  170-178.  DOI: 10.16139/j.1007-9610.2024.02.13
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Objective To establish and validate a Nomogram model for predicting the overall survival (OS) of the patients with intrahepatic cholangiocarcinoma (ICC) based on domestic multicenter data, and screen the beneficiaries of adjuvant chemotherapy based on the prediction model. Methods From December 2011 to December 2017, the data of 278 patients with postoperative pathological diagnosis of ICC from 4 medical centers in our country were collected retrospectively COX regression model was used to screen the independent risk factors of OS and constructed a Nomogram model. This model was used to stratify the risk of OS for all patients and to screen the beneficiaries of adjuvant chemotherapy. Results A total of 278 patients were enrolled, and 23 cases(8.3%) received adjuvant chemotherapy. COX multivariate analysis showed that drinking history, ECOG score, method of hepatectomy, lymph node status, number of tumors, and tumor differentiation were independent risk factors for postoperative OS. The Nomogram model had a C-index of 0.690(95% CI: 0.646-0.734) in the training cohort and 0.740(95% CI: 0.863-0.617) in the validation cohort. According to risk stratification by Nomogram model, in the high-risk group there was a statistically significant difference in survival between adjuvant chemotherapy and non-adjuvant chemotherapy (P=0.033), whereas in the low-risk group, there was no significant difference in survival(P=0.59). Conclusion Nomogram model based on independent risk factors of OS demonstrated excellent predictive capability for survival and could be used to screen, and identify the patients with ICC who benefit from adjuvant chemotherapy.

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Case report
Solitary cervical submental metastasis of papillary thyroid carcinoma: one case report
TONG Yanhua, CHEN Yingzhen, WANG Qiongmei, WANG Caijiao, ZHU Qing, WU Anni, LU Yu, YAO Jiejie
2024, 29 (02):  179-181.  DOI: 10.16139/j.1007-9610.2024.02.14
Abstract ( 25 )   HTML ( 0 )   PDF (3421KB) ( 3 )  

Solitary cervical submental nodule is a relatively rare case in clinical procedure and prone to miss diagnosis. Differential diagnosis with various head and neck diseases is necessary. This article reported a case of solitary cervical submental metastasis of papillary thyroid carcinoma received in the department of surgery, Civil Aviation Shanghai Hospital, Ruijin Gubei Branch, Shanghai Jiao Tong University School of Medicine. The patient came to the outpatient clinic for treatment due to "consciously larger submental tubercle than before". Ultrasound examination revealed suspicious lesions in both the thyroid and submental regions. Ultrasound-guided final needle aspiration biopsy diagnosed as malignant tumor. Surgical resection was performed and the central group lymph nodes dissected Pathological examination confirmed papillary thyroid carcinoma with solitary submental metastasis. This article reported the clinical diagnosis and treatment of this case, in order to improve the disease recognition for clinicians, and make differential diagnosis with other rare neck diseases, and avoid missing diagnoses.

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Review
Etiology, classification and diagnosis of congenital biliary dilatation
GAO Zhenhua, WU Shuodong
2024, 29 (02):  182-185.  DOI: 10.16139/j.1007-9610.2024.02.15
Abstract ( 46 )   HTML ( 1 )   PDF (848KB) ( 5 )  

The etiology of congenital biliary dilatation (CBD) is still unclear. Currently, abnormal pancreatico-bile duct confluence is the mainstream theory. In terms of classification, Todani classification is the most widely used. On the other hand, Dong's classification which proposed by Dong Jiahong and his colleagues has guiding significance for the selection of surgical methods. CBD is difficult to detect and diagnose because of the poor specificity of clinical symptoms, and it is often necessary to make a preliminary diagnosis based on the medical history, and it is also quite dependent on the assistance of imaging. Serological examination also plays a key role in the diagnosis of CBD because of its convenience and high acceptance. This article reviewed the etiology, classification and diagnosis of CBD.

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