Ultrasound-Guided Continuous Thoracic Paravertebral Block Improves Patientʼs Quality of Recovery After Open Hepatectomy: A Randomized, Double-Blind, Placebo-Controlled Trial

Background Ultrasound-guided continuous thoracic paravertebral block can provide pain-relieving and opioid-sparing effects in patients receiving open hepatectomy.We hypothesize that these effects may improve the quality of recovery(QoR)after open hepatectomy.Methods Seventy-six patients undergoing open hepatectomy were randomized to receive a continuous thoracic paravertebral block with ropivacaine(CTPVB group)or normal saline(control group).All patients received patient-controlled intravenous analgesia with morphine postoperatively for 48 hours.The primary outcome was the global Chinese 15-item Quality of Recovery score on postoperative day 7,which was statistically analyzed using Student’s t-test.Results Thirty-six patients in the CTPVB group and 37 in the control group completed the study.Compared to the control group,the CTPVB group had significantly increased global Chinese 15-item Quality of Recovery scores(133.14±12.97 vs.122.62±14.89,P=0.002)on postoperative day 7.Postoperative pain scores and cumulative morphine consumption were significantly lower for up to 8 and 48 hours(P<0.05;P=0.002),respectively,in the CTPVB group.Conclusion Perioperative CTPVB markably promotes patient’s QoR after open hepatectomy with a profound analgesic effect in the early postoperative period.

Clinical diagnosis and treatment of alpha-fetoprotein-negative small hepatic lesions

Objective： We examined 103 cases over the last five years and discussed diagnosis and treatment of alpha- fetoprotein （AFP）-negative small hepatic lesions. Background： Small hepatic lesions （less than 2 cm in diameter） usually have no typical imaging characteristics and therefore are difficult to diagnose, especially when AFP tests provide a negative result. Methods： A total of 103 patients with AFP-negative small hepatic lesions from January 2003 to December 2008 were retrospectively reviewed. Differential diagnosis was performed by digital subtraction angiography （DSA）, dynamic contrast-enhanced magnetic resonance imaging （DCE-MRI）, contrast-enhanced ultrasound （CEUS）, or positron emission tomography-computed tomography （PET-CT） based on the multiplicity of lesions. Ninety-four patients with suspected cancers underwent partial hepatectomy. Clinical data were collected from hospital records and follow-up questionnaires. Results： Hepatocellular carcinoma （HCC） diagnostic sensitivity of DSA, DCE-MRI, CEUS and PET-CT was 88.2%, 93.9%, 88.9% and 88.9%, respectively. The surgery-related complication rate was 6.4%. Prognosis was good, with 1- and 3-year survival rates of 98.8% and 76.1%, respectively. Conclusions： DSA, DCE-MRI, CEUS and PET-CT are valuable for diagnosis of small hepatic lesions. Partial hepatectomy is a preferred surgical procedure. Surgery for small liver cancers usually has little risk and good prognosis, therefore it can be actively applied in suspected HCC cases.

Advances in the diagnosis and treatment of Ig G4-related sclerosing cholangitis: a review

Immunoglobulin G4-related sclerosing cholangitis(Ig G4-SC) is an Ig G4-related disease characterized by bile duct fibroinflammatory wall-thickening and stenosis, resulting in obstruction jaundice, weight loss. Different regions of the bile duct can be involved, with the distal region being the most common. Ig G4-SC can also have other organ involvement, such as the pancreas, urinary tract, salivary glands and lacrimal glands. In clinical practice, the manifestation of Ig G4-SC is very similar to cholangiocarcinoma(CC) and primary sclerosing cholangitis(PSC), as well as pancreatic malignancies, while the treatment and prognosis are totally different. Japanese researchers ever established the clinical diagnostic criteria in 2012:(1) characteristic biliary imaging findings;(2) elevated serum Ig G4 concentrations;(3) the coexistence of Ig G4-related diseases except those of the biliary tract; and(4) characteristic histopathological features. According to our observations, Ig G4-SC can be distinguished from CC with 100% specificity only at a cutoff of six times the upper normal limit. Imaging findings have low specificity for diagnosis, with the exception of intraductal ultrasonography, which can reflect the lesion with relatively high specificity. Ig G4 plasma cell infiltration can be found in bile duct biopsy tissue, although this procedure is difficult. According to recent studies, the treatment of Ig G4-SC relies mainly on corticosteroids. Following steroid treatment, most Ig G4-SC patients can recover and their symptoms are resolved although a few patients relapse after steroid withdrawal. Maintenance of steroid therapy or alternative drugs is necessary in such cases. There is, however, no strong evidence for malignant transformation in Ig G4-SC.

Application and Progress of Cultured Models of Gallbladder Carcinoma

Gallbladder carcinoma (GBC) is a malignant tumor of the bil-iary system that is aggressive, difficult to detect early, and has a low surgical resection rate and poor prognosis. Ap-propriate in vitro growth models are expected to focus on the study of the biological behavior and assess treatment effects. Nonetheless, cancer initiation, progression, and in-vasion include spatiotemporal changes and changes in the cell microenvironment intracellular communication, and in-tracellular molecules, making the development of in vitro growth models very challenging. Recent advances in bioma-terial methods and tissue engineering, particularly advances in bioprinting procedures, have paved the way for advances in the creative phase of in vitro cancer research. To date, an increasing number of cultured models of gallbladder disease have emerged, such as two-dimensional (2D) GBC growth cell cultures, three-dimensional (3D) GBC growth cell cul-tures, xenograft models, and 3D bioprinting methods. These models can serve as stronger platforms, focusing on tumor growth initiation, the association with the microenvironment, angiogenesis, motility, aggression, and infiltration. Bioprint-ed growth models can also be used for high-throughput drug screening and validation, as well as translational opportuni-ties for individual cancer therapy. This study focused on the exploration, progress, and significance of the development of GBC cultural models. We present our views on the short-comings of existing models, investigate new innovations, and plan future improvements and application possibilities for cancer models.

42,573 cases of hepatectomy in China： a multicenter retrospective investigation

Hepatectomy is currently routinely performed in most hospitals in China. China owns the largest population of liver diseases and the biggest number of liver resection cases. A nationwide multicenter retrospective investigation involving 112 hospitals was performed, and focused on liver resection for patients with hepatocellular carcinoma(HCC). 42,573 cases of hepatectomy were enrolled, and 18,275 valid cases of liver resection for HCC patients were selected for statistical analysis. The epidemiology of HCC, distribution of hepatectomy, postoperative complications and prognosis were finally analyzed. In the 18,275 HCC patients,81% had hepatitis B virus infection and 10% had hepatitis C virus infection. 38% of the HCC patients had normal Alphafetoprotein(AFP) level, and other 35% had an AFP level lower than 400 ng mL^(-1). In the study period, 97% of the hepatectomy for HCC were treated with open surgery, and 23.81% had vascular exclusion techniques. The operation time was(191.7±105.6) min,the blood loss was(546.0±562.8) m L, and blood transfusion was(543.0±1,035.2) m L. The median survival for HCC patients was 631 days, with 1-, 3-, and 5-year overall survival of 73.2%, 28.8% and 19.6%, respectively. Liver cirrhosis, multiple nodules,tumor thrombosis and high AFP level were risk factors that affect postoperative survival.

Pembrolizumab combined with lenvatinib as non-first-line therapy in patients with refractory biliary tract carcinoma

Background:A therapeutic strategy involving combined treatment with lenvatinib plus pembrolizumab(LEP)has demonstrated a relatively high antitumor response in several solid tumors;however,the efficacy and safety of LEP in patients with refractory bile tract carcinoma(BTC)remains unknown.Methods:This is a single-arm study for a preliminary assessment of the efficacy and tolerability of LEP in patients who experienced progression from prior systemic treatments.Pre-treatment tumor tissues were collected to retrospectively evaluate the expression status of PDL1.Results:Thirty-two patients received second-line and above treatment with LEP.Overall,the objective response rate(ORR)was 25%,the disease control rate(DCR)was 78.1%,and the clinical benefit rate(CBR)was 40.5%.The median progression-free survival(PFS)was 4.9 months(95%CI:4.7–5.2 months),and the median overall survival(OS)was 11.0 months(95%CI:9.6–12.3 months).For tolerability,no grade 5 serious adverse events(AEs)were reported.All patients had any-grade AEs,and 59.3%of the patients experienced grade 3 AEs,while only 1 patient experienced a grade 4 AE of stomach bleeding.Fatigue was the most common AE,followed by hypertension and elevated aminotransferase levels.Retrospective analysis for PDL1 expression revealed that PDL1 positive tumor cells were associated with improved clinical benefits and survival outcomes.Conclusions:LEP is a promising alternative as a non-first-line therapeutic regimen for patients with refractory BTC.Furthermore,well-designed prospective clinical trials with a control arm are still needed to obtain more evidences to confirm the efficacy and safety of this particular regimen as well as the role of PDL1 expression.

Downstaging and resection of hepatocellular carcinoma in patients with extrahepatic metastases after stereotactic therapy

Background:A combination of tyrosine kinase inhibitors(TKIs)and anti-PD-1 antibodies with local regional therapy has elicited yield substantial clinical benefits in patients who have hepatocellular carcinoma(HCC)with extrahepatic metastases.Using this treatment strategy to convert HCC patients with extrahepatic metastases from unresectable to resectable has not yet been reported.Methods:Consecutive hepatocellular carcinoma patients with extrahepatic metastases who received first-line therapy with a combination of TKIs and anti-PD-1 antibodies and at least one local regional therapy were analysed.Results:Nine patients with localized disease who received first-line systemic therapy were enrolled.At baseline,all of them had oligometastatic disease,namely,Barcelona Clinic Liver Cancer stage C(or Chinese Liver Cancer stage IIIB).The most common treatment administered was lenvatinib plus anti-PD-1 antibody and transarterial chemoembolization,and the median time span from systemic therapy to surgery was 3.2(IQR,2.8-6.2)months.Three patients achieved a pathological complete response.Six patients underwent laparoscopic surgery,and the other 3 patients underwent open surgery.After a median follow-up of 10.2(IQR,8.6-20.0)months,7 patients survived without disease recurrence,and 2 experienced tumour recurrence.All patients had any-grade AEs,and 55.6%of the patients experienced grade 3 AEs.Fatigue was the most common AE,followed by elevated aminotransferase levels and hypertension.Conclusions:Stereotactic therapy is a feasible conversion therapy for HCC patients with extrahepatic metastases to become resectable.This is the first study to analyse therapeutic outcomes of patients receiving these therapies for HCC with extrahepatic metastases.

Chinese expert consensus on conversion therapy for hepatocellular carcinoma(2021 edition)

Recent advances in systemic and locoregional treatments for patients with unresectable or advanced hepatocellular carcinoma(HCC)have resulted in improved response rates.This has provided an opportunity for selected patients with initially unresectable HCC to achieve adequate tumor downstaging to undergo surgical resection,a‘conversion therapy’strategy.However,conversion therapy is a new approach to the treatment of HCC and its practice and treatment protocols are still being developed.Review the evidence for conversion therapy in HCC and develop consensus statements to guide clinical practice.Evidence review:Many research centers in China have accumulated significant experience implementing HCC conversion therapy.Preliminary findings and data have shown that conversion therapy represents an important strategy to maximize the survival of selected patients with intermediate stage to advanced HCC;however,there are still many urgent clinical and scientific challenges for this therapeutic strategy and its related fields.In order to summarize and learn from past experience and review current challenges,the Chinese Expert Consensus on Conversion Therapy for Hepatocellular Carcinoma(2021 Edition)was developed based on a review of preliminary experience and clinical data from Chinese and non-Chinese studies in this field and combined with recommendations for clinical practice.Sixteen consensus statements on the implementation of conversion therapy for HCC were developed.The statements generated in this review are based on a review of clinical evidence and real clinical experience and will help guide future progress in conversion therapy for patients with HCC.

Multidisciplinary management of recurrent and metastatic hepatocellular carcinoma after resection: an international expert consensus

Hepatocellular carcinoma (HCC) is the sixth-most common cancer and the third leading cause of cancer-related death in the world. However, 40–70% patients eventually suffer from postoperative recurrence within 5 years. HCC recurrence after surgery severely affects prognosis of the patients. Nevertheless, there is an opportunity to improve patients' prognosis if doctors and researchers can recognize the importance of a standardized perioperative management and study it in clinical and pre-clinical settings. Hence, based on our own experience and published studies from other researchers, we develop this consensus regarding multidisciplinary management of locally recurrent and metastatic hepatocellular carcinoma after resection. This consensus consists of the entire course of recurrent hepatocellular carcinoma (RHCC) management, including prediction of recurrence, prevention, diagnosis, treatment and surveillance of RHCC. Consensus recommendations are presented with grades of evidences (Ia, Ib, IIa, IIb, III and IV), and strength ofrecommendations (A, B, C, D and E). We also develop a decision-making path for RHCC treatment, which can intuitively demonstrate the management for RHCC. It is hoped that we may make some effort to standardize the management of RHCC and ultimately understand how to improve outcomes.

患者来源的类器官:一种有前景的个体化癌症治疗模式

Cancer has remained one of the biggest challenges for human health during the past few decades despite major advances in medicine[1].Poor prognosis of cancer is mainly caused by a lack of effective treatment.Moreover,many patients cannot receive appropriate treatment despite early diagnosis.High heterogeneity is a tumor characteristic and different types of cancer usually vary in clinical features and tumorigenic mechanisms,which results in different responses to drugs[2].How to predict accurately the patient’s response to drugs and choose personalized treatment is one of themain concerns of doctors.

基于人工智能的影像组学在肝病中的应用现状

影像组学是指使用计算机从不同类型的影像图像中提取大量信息, 形成各种可定量的特征, 然后选取一些相关的特征通过人工智能方法构建模型, 用以预测一些临床问题(如诊断、治疗、预后)的结局。将影像组学应用于肝病研究将有助于肝病的早期诊断和早期治疗, 并改善患者生存和治愈率。影像组学的研究目前方兴未艾, 未来可能还会有巨大进展。因此, 我们总结了影像组学在肝病中的研究现状, 并指出相关不足及未来研究方向。

Expert consensus on organizing the multidisciplinary team(MDT) diagnosis and treatment of hepato-pancreato-biliary diseases in China

Multidisciplinary team(MDT) discussion has been well established in some European countries and widely carried out in various clinical professional fields(Festen et al.,2021;Fleissig et al.,2006).Many studies have reported the benefits of MDT,including improving survival and quality of cancer care(Munro et al.,2015;Nixon et al.,2021;Tsai et al.,2020).

Giant hepatocellular carcinoma

A 40-year-old female presented with progressive abdominal enlargement for 6 months(Panel A),along with severe abdominal distension and amenorrhea.She had not gone to hospital because she assumed herself to be pregnant,until the belly grew out of control.A giant lesion in abdomen was detected by computed tomography(Panel B).

The first-line treatment for unresectable hepatocellular carcinoma patients: lenvatinib versus sorafenib, or beyond?

In the past decade, sorafenib has been the only approved molecular-targeted agent for unresectable hepatocellular carcinoma (uHCC) without any authentic challenges. There has been an urging need for alternatives or superior options for a long while (1-3). At least 25 molecular-targeted drugs emerged in the past 15 years and had been tested for the efficacy and safety in treating uHCC, yet most of those trials have failed to show positive results (Table 1).

A brief comment on liver resection for hepatocellular carcinoma

Although only 30-40%of patients with hepatocellular carcinoma(HCC)are eligible for surgery,it remains the most feasible and efficient treatment[1,2].The three most important factors that have led to reduce mortality,with a 70%expectation of 5-year survival,are:i)better liver function assessment,ii)understanding of the segmental liver anatomy through more accurate imaging studies and iii)technical advances in surgical procedures[3].

Tumor-immune Co-evolution in hepatocellular carcinoma and itsimplication for immunotherapy resistance

1.Introduction In recent years,investigators have witnessed great progress in understanding the tumor microenvironment(TME)and evolution,which has been accompanied by a substantial number of newly developed targeted therapies and immunotherapies.Tumors are capable of escaping immune surveillance in the context of both spontaneous immune response and immunotherapies,and these two immune evasion processes share many overlapping mechanisms,such as human leukocyte antigen loss of heterozygosity(HLA-LOH)and immunoediting[1].For hepatocellular carcinoma(HCC),numerous treatment strategies targeting the TME have been proposed in recent years[2,3].Among these strategies,immune-checkpoint inhibitors(ICIs)have been found to be a promising therapeutic choice[4–6].The combination of atezolizumab(anti--programmed death-ligand 1,PD-L1)and bevacizumab(anti-vascular endothelial growth factor,VEGF)antibodies demonstrated significantly better overall and progression-free survival than the kinase inhibitor sorafenib in patients with unresectable HCC in a phase III trial[4],and this combination was established as a first-line treatment for advanced HCC.However,the response rate for ICIs was limited[4–6],and it was reported that nonalcoholic steatohepatitis-related HCC was less responsive to ICIs than other HCCs[7].Given the clinical importance of tolerance to immunotherapy in HCC,tumor-immune co-evolution deserves more attention and may provide novel ideas for developing new combination therapies that target multiple mechanisms of immunotherapy resistance.

Alcohol consumption as a cause of cancer: urging for more mechanism study

Alcohol consumption is a major health problem worldwide.It has been identified as a Group 1 carcinogen to humans by The International Agency for Research on Cancer(IARC)in 2006,yet up to 38.1%of the world's population aged above 15 years old are regular drinkers.Globally,estimates suggest that 5.5%of cancer cases and 5.8%of cancer-related deaths are attributable to alcohol drinking(1).Epidemiologic studies unequivocally acknowledge chronic alcohol drinking as an important risk factor for different types of cancers,including those of upper aerodigestive tract(UADT)(oral cavity,pharynx,larynx and esophagus),liver,pancreas,female breast,colon and blood.However,there are studies suggest that light-to-moderate alcohol drinking appears to trigger anti-inflammatory mechanisms,reducing the risk of coronary heart disease and dementia,and provides protection against type II diabetes(2).And in traditional Chinese medicine(TCM),wine,a popular alcohol beverage,is considered rather beneficial in health preservation.