A pilot study on combination of cryosurgery and ^(125)iodine seed implantation for treatment of locally advanced pancreatic cancer

AIM: To study the therapeutic value of combination o cryosurgery and 125iodine seed implantation for locally advanced pancreatic cancer. METHODS: Forty-nine patients with locally advanced pancreatic cancer (males 36, females 13), with a median age of 59 years, were enrolled in the study. Twelve patients had liver metastases. In all cases the tumors were considered unresectable after a comprehensive evaluation. Patients were treated with cryosurgery, which was performed intraoperatively or percutaneously unde guidance of ultrasound and/or computed tomography (CT), and 125iodine seed implantation, which was performed during cryosurgery or post-cryosurgery under guidance of ultrasound and/or CT. A few patients received regional celiac artery chemotherapy. RESULTS: Thirteen patients received intraoperative cryosurgery and 36 received percutaneous cryosurgery Some patients underwent repeat cryosurgery. 125Iodine seed implantation was performed during freezing procedure in 35 patients and 3-9 d after cryosurgery in 14 cases. Twenty patients, 10 of whom had hepaticmetastases received regional chemotherapy. At 3 mo after therapy, CT was repeated to estimate tumor response to therapy. Most patients showed varying degrees of tumor necrosis. Complete response (CR) of tumor was seen in 20.4% patients, partial response (PR), in 38.8%, stable disease (SD), in 30.6%, and progressive disease (PD), in 10.2%. Adverse effects associated with cryosurgery included upper abdomen pain and increased serum amylase. Acute pancreatitis was seen in 6 patients one of whom developed severe pancreatitis. All adverse effects were controlled by medical management with no poor outcome. There was no therapy-related mortality. During a median follow-up of 18 mo (range of 5-40), the median survival was 16.2 mo, with 26 patients (53.1%) surviving for 12 mo or more. Overall, the 6-, 12-, 24- and 36-mo survival rates were 94.9%, 63.1%, 22.8% and 9.5%, respectively. Eight patients had survival of 24 mo or more. The patient with the longest survival (40 mo) is still living without evidence of tumor recurrence. CONCLUSION: Cryosurgery, which is far less invasive than conventional pancreatic resection, and is associated with a low rate of adverse effects, should be the treatment of choice for patients with locally advanced pancreatic cancer. 125Iodine seed implantation can destroy the residual surviving cancer cells after cryosurgery. Hence, a combination of both modalities has a complementary effect.

Predictive value of D-dimer for portal vein thrombosis after portal hypertension surgery in hepatitis B virus-related cirrhosis

AIM: To evaluate the predictive value of D-dimer as a predictive indicator of portal vein thrombosis (PVT) after portal hypertension surgery in hepatitis B virus-related cirrhosis. METHODS: A prospective study was carried out in 52 patients who had undergone surgery for portal hypertension in hepatitis B virus-related cirrhosis. Changes in perioperative dynamic D-dimer were observed. The sensitivity, specifi city, positive predictive values and negative predictive values of D-dimer were calculated, and ROC curves were analyzed. RESULTS: The D-dimer levels in the group developing postoperative PVT was signifi cantly higher than those in the group not developing PVT (P = 0.001), and the ROC semi-quantitative and qualitative analysis of D-dimer showed a moderate predictive value in PVT (semi- quantitative value Az = 0.794, P = 0.000; qualitative analysis: Az = 0.739, P = 0.001). CONCLUSION: Dynamic monitoring of D-dimer levels in patients with portal hypertension after surgery can help early diagnosis of PVT, as in cases where the D-dimer levels steadily increase and exceed 16 μg/mL, the possibility of PVT is very high.

Sequential use of transarterial chemoembolization and percutaneous cryosurgery for hepatocellular carcinoma

AIM: To evaluate the efficacy of sequential use of transarterial chemoembolization (TACE) and percutaneous cryosurgery for unresectable hepatocellular carcinoma (HCC). METHODS: Four hundred and twenty patients were enrolled in this study. The patients, who were considered to have unresectable tumors due to their location or size or comorbidity, were divided into sequential TACE-cryosurgery (sequential) group (n = 290) and cryosurgery alone (cryoalone) group (n = 130). Patients in the sequential group tended to have larger tumors and a greater number of tumors than those in the cryo-alone group. Tumors larger than 10 cm in diameter were only seen in the sequential group. TACE was performed with the routine technique and percutaneous cryosurgery was conducted under the guidance of ultrasound 2-4 wk after TACE. RESULTS: During a mean follow-up period of 42 ± 17 mo (range, 24-70 mo), the local recurrence rateat the ablated area was 17% for all patients, 11% and 23% for patients in sequential group and cryoalone groups, respectively (P = 0.001). The overall 1-, 2-, 3-, 4and 5-year survival rate was 72%, 57%, 47%, 39% and 31%, respectively. The 1and 2-year survival rates (71% and 61%) in sequential group were similar to those (73% and 54%) in cryo-alone group (P = 0.69 and 0.147), while the 4and 5-year survival rates were 49% and 39% in sequential group, higher than those (29% and 23%) in cryo-alone group (P = 0.001). Eighteen patients with large HCC (> 5 cm in diameter) survived for more than 5 years after sequential TACE while no patient with large HCC (> 5 cm in diameter) survived more than 5 years after cryosurgery. The overall complication rate was 24%, and the complication rates were 21% and 26% for the sequential and cryo-alone groups, respectively (P = 0.06). The incidence of hepatic bleeding was higher in cryo-alone group than in sequential group (P = 0.02). Liver crack only occurred in two patients of the cryoalone group. CONCLUSION: Pre-cryosurgical TACE can increase the cryoablation efficacy and decrease its adverse effects, especially bleeding. Sequential TACE and cryosurgery may be the better procedure for unresectable HCC, especially for large HCC.

MUC1与ER、PR在乳腺癌组织中的表达及意义(英文)

目的 检测MUC1、ER和PR在乳腺癌中的表达 ,探讨其在乳腺癌的诊断和预后评估中的意义。方法 采用免疫组化方法检测了 86例乳腺癌及 4 0例乳腺良性病变组织中MUC1、ER和PR的表达水平。结果 乳腺良性病变组织中可见MUC1阳性表达 ,而乳腺癌组织中MUC1高表达 ,MUC1在乳腺癌组织中的高表达与乳腺良性病变组织之间存在显著性差异 (P <0 .0 1)。ER、PR在乳腺癌与乳腺良性病变组织中的阳性表达之间无显著性差异 (P >0 .0 5 )。MUC1及PR在乳腺癌组织中的表达与预后无明显相关 (P >0 .0 5 ) ,ER在乳腺癌组织中阳性表达与乳腺癌的良好预后明显相关 (P <0 .0 1)。结论 MUC1在乳腺癌组织中的高表达是乳腺良恶性病变的鉴别诊断指标 ,与乳腺癌的预后无明显相关 ,ER阳性表达是乳腺癌预后良好的指标。

Choice of approach for hepatectomy for hepatocellular carcinoma located in the caudate lobe:Isolated or combined lobectomy?

AIM:To investigate the significance of the surgical approaches in the prognosis of hepatocellular carcinoma(HCC) located in the caudate lobe with a multivariate regression analysis using a Cox proportional hazard model.METHODS:Thirty-six patients with HCC underwent caudate lobectomy at a single tertiary referral center between January 1995 and June 2010.In this series,left-sided,right-sided and bilateral approaches were used.The outcomes of patients who underwent isolated caudate lobectomy or caudate lobectomy combined with an additional partial hepatectomy were compared.The survival curves of the isolated and combined resection groups were generated by the Kaplan-Meier method and compared by a log-rank test.RESULTS:Sixteen(44.4%) of 36 patients underwent isolated total or partial caudate lobectomy whereas 20(55.6%) received a total or partial caudate lobectomy combined with an additional partial hepatectomy.The median diameter of the tumor was 6.7 cm(range,2.1-15.8 cm).Patients who underwent an isolated caudate lobectomy had significantly longer operative time(240 min vs 170 min),longer length of hospital stay(18 d vs 13 d) and more blood loss(780 mL vs 270 mL) than patients who underwent a combined caudate lobectomy(P < 0.05).There were no perioperative deaths in both groups of patients.The complication rate was higher in the patients who underwent an isolated caudate lobectomy than in those who underwent combined caudate lobectomy(31.3% vs 10.0%,P < 0.05).The 1-,3-and 5-year disease-free survival rates for the isolated caudate lobectomy and the combined caudate lobectomy groups were 54.5%,6.5% and 0% and 85.8%,37.6% and 0%,respectively(P < 0.05).The corresponding overall survival rates were 73.8%,18.5% and 0% and 93.1%,43.6% and 6.7%(P < 0.05).CONCLUSION:The caudate lobectomy combined with an additional partial hepatectomy is preferred because this approach is technically less demanding and offers an adequate surgical margin.

Prognostication and response assessment in liver and pancreatic tumors:The new imaging

Diffusion-weighted imaging(DWI), dynamic contrastenhanced magnetic resonance imaging(DCE-MRI) and perfusion computed tomography(CT) are technical improvements of morphologic imaging that can evaluate functional properties of hepato-bilio-pancreatic tumors during conventional MRI or CT examinations.Nevertheless, the term "functional imaging" is commonly used to describe molecular imaging techniques, as positron emission tomography(PET)CT/MRI, which still represent the most widely used methods for the evaluation of functional properties of solid neoplasms; unlike PET or single photon emission computed tomography, functional imaging techniques applied to conventional MRI/CT examinations do not require the administration of radiolabeled drugs or specific equipments. Moreover, DWI and DCE-MRI can be performed during the same session, thus providing a comprehensive "one-step" morphological and functional evaluation of hepato-bilio-pancreatic tumors. Literature data reveal that functional imaging techniques could be proposed for the evaluation of these tumors before treatment, given that they may improve staging and predict prognosis or clinical outcome. Microscopic changes within neoplastic tissues induced by treatments can be detected and quantified with functional imaging,therefore these techniques could be used also for posttreatment assessment, even at an early stage. The aim of this editorial is to describe possible applications of new functional imaging techniques apart frommolecular imaging to hepatic and pancreatic tumors through a review of up-to-date literature data, with a particular emphasis on pathological correlations,prognostic stratification and post-treatment monitoring.

Ductal adenocarcinoma of the pancreatic head:A focus on current diagnostic and surgical concepts

Complete surgical resection still remains the only possibility of curing pancreatic cancer,however,only 10% of patients undergo curative surgery.Pancreatic resection currently remains the only method of curing patients,and has a 5-year overall survival rate between 7%-34% compared to a median survival of 3-11 mo for unresected cancer.Pancreatic surgery is a technically demanding procedure requiring highly standardized surgical techniques.Nevertheless,even in experienced hands,perioperative morbidity rates(delayed gastric emptying,pancreatic fistula etc.) are as high as 50%.Different strategies to reduce postoperative morbidity,such as different techniques of gastroenteric reconstruction(pancreatico-jejunostomy vs pancreatico-gastrostomy),intraoperative placement of a pancreatic main duct stent or temporary sealing of the main pancreatic duct with fibrin glue have not led to a significant improvement in clinical outcome.The perioperative application of somatostatin or its analogues may decrease the incidence of pancreatic fistulas in cases with soft pancreatic tissue and a small main pancreatic duct(< 3 mm).The positive effects of external pancreatic main duct drainage and antecolic gastrointestinal reconstruction have been observed to decrease the rate of pancreatic fistulas and delayed gastric emptying,respectively.Currently,the concept of extended radical lymphadenectomy has been found to be associated with higher perioperative morbidity,but without any positive impact on overall survival.However,there is growing evidence that portal vein resections can be performed with acceptable low perioperative morbidity and mortality but does not achieve a cure.

Hypoxia preconditioning protects Ca^(2+)-ATPase activation of intestinal mucosal cells against R/I injury in a rat liver transplantation model

AIM To investigate the effect of ischaemia and reperfusion(I/R) injury on the Ca^(2+)-ATPase activation in the intestinal tissue of a rat autologous orthotopic liver transplantation model and to determine if hypoxia preconditioning(HP) therapy induces HIF-1α to protect rat intestinal tissue against I/R injury.METHODS Rats received non-lethal hypoxic preconditioning therapy to induce HIF-1α expression. We used an autologous orthotopic liver transplantation model to imitate the I/R injury in intestinal tissue. Then, we detected the microstructure changes in small intestinal tissues, Ca^(2+)-ATPase activity, apoptosis, and inflammation within 48 h postoperatively. RESULTS HIF-1α expression was significantly increased in intestinal tissue at 12 h postoperatively in rats that were exposed to a hypoxic environment for 90 min compared with a non-HP group(HP vs AT, P = 0.0177). Pathological analysis was performed on the intestinal mucosa cells, and the cells in the HP group appeared healthier than the cells in the AT group. The Ca^(2+)-ATPase activity in the small intestinal cells in the AT group was significantly lower after the operation, and the Ca^(2+)-ATPase activity in the HP group recovered faster than that in the AT group at 6 h postoperatively(HP vs AT, P = 0.0106). BCL-2 expression in the HP group was significantly higher than that in the AT group at 12 h postoperatively(HP vs AT P = 0.0010). The expression of the inflammatory factors NO, SOD, IL-6, and TNF-α was significantly lower in the HP group than in the AT group.CONCLUSION Hypoxia-induced HIF-1α could protect intestinal mucosal cells against mitochondrial damage after I/R injury. HP could improve hypoxia tolerance in small intestinal mucosal cells and increase Ca^(2+)-ATPase activity to reduce the apoptosis of and pathological damage to intestinal cells. HP could be a useful way to promote the earlier recovery of intestinal function after graft procedure.

Difference in gene expression of macrophage between normal spleen and portal hypertensive spleen idendified by cDNA microarray

AIM: To identify the difference in gene expression of microphage (Mφ) between normal spleen and portal hypertensive spleen using cDNA microarrays and find new gene functions associated with hypersplenism in portal hypertension. METHODS: The Biostar-H140s chip containing 14 112 spots of cDNAs were used to investigate the difference of the expression. The total RNA extracted from macrophages isolated from both normal spleen and portal hypertensive spleen was reversely transcribed to cDNA with the incorporation of fluorescent (cy3 and cy5) labeled dCTP to prepare the hybridization probes. After hybridization, the gene chip was scanned for the fluorescent intensity. The differentially expressed genes were screened. That was repeated three times, and only the genes which had differential expression in all three chips were considered to be associated with hypersplenism in portal hypertension. RESULTS: Eight hundred and ninety-six, 1330 and 898 genes were identified to be differentially expressed in three chips, respectively. One hundred and twenty-one genes (0.86%) were identified to be differentially expressed in all three chips, including 21 up-regulated genes and 73 down-regulated genes. The differentially expressed genes were related to ionic channel and transport protein, cyclin, cytoskeleton, cell receptor, cell signal conduct, metabolism, immune, and so on. These genes might be related to the hypersplenism in portal hypertension.CONCLUSION: The investigations based on cDNA microarray can screen differentially expressed genes of macrophages between normal spleen and portal hypertensive spleen, thus may provide a new idea in studying the pathogenesis of hypersplenism in portal hypertension.

SURGICAL TREATMENT OF HILAR BILE DUCT CARCINOMA

From June, 1986 to June 1989, 24 cases of hilar bile duct carcinoma were explored in the Surgical Department of General Hospital of PLA, 16/24 cases were resected, a resectability rate of 66%. The increase of resectability rate was due to earlier recognition of this condition and the extension of surgery, including major resection of liver as well as radical dissection of the hepato-duodenal ligament and repairative operations on the blood vessels. Among these 16 cases, major hepatic resection was performed in 10 cases, in which, 3 cases of resections of the middle lobe of the liver were done instead of right or extended right lobectomy. No operative mortality in the 30 days' postoperative period, but the postoperative morbidity rate was still high and most of the complications were related to biliary leakage and infection. Three patients died in the follow up period at 6, 14 and 15 months respectively. All of them died from biliary infection. The remaining 13 patients were still alive, the longest being 40 months and the average living time was 16.1 months. Probably, lowering of the operative mortality rate and morbidity rate are still the most important considerations in the surgical treatment of hilar carcinoma at the present time. Extensive liver resection especially on the right side, carried a high mortality rate in the deeply jaundiced patients. We considered that preoperative PTCD was of much less value than that used in lower bile duct obstruction such as tumors of the periampullary region. Preservation of the superior and posterior portion of the right lobe of the liver may be of advantages as to lowering postoperative hepatic failure and infection of the right subphrenic space as observed in this series of cases.

Hepatic veins as a site of clot formation following liver resection

Pulmonary embolism occurs more frequently after hepatectomy than previously thought but is infrequently associated with peripheral deep vein thrombosis. In this paper, we report 2 cases of postoperative hepatic vein thrombosis after liver resection. Both patients had undergone major hepatectomy of a non-cirrhotic liver largely exposing the middle hepatic vein. Clots were incidentally found in the middle hepatic vein 4 and 17 d after surgery despite routine systemic thrombo-prophylaxis with low molecular weight heparin. Coagulation of the transition plan in a context of mutation of the prothrombin gene and inflammation induced biloma were the likely predisposing conditions. Clots disappeared following curative anticoagulation. We conclude that thrombosis of hepatic veins may occur after liver resection and is a potential source of pulmonary embolism.

术中超声在冷循环射频治疗肝脏肿瘤中的作用(英文)

目的将在肝的癌的凉爽尖端的射频脱离(RFA ) 探索 intraoperative ultrasonography (IOUS ) 的可行性和效率。肝的癌的 31 个病人在这被注册的方法学习。在哆开的, 开放的, 切开, 切断电路, 断电外科的凉爽尖端的射频脱离的过程， IOUS 被使用，指导并且监视 RFA 在的过程估计肝的损害即时。在 intraoperative ultrasonography 的指导下面的结果，在所有病人的户外 surgical RFA 顺利继续。七另外的肝的损害被发现那没在外科手术前的成像被检测。外科手术前的 MRI 报导的假积极局灶性损害被 IOUS 精确地排除。结论 Intraoperative ultrasonography 比在发现损害错过的平常的成像技术优异，避免象胆汁管和容器的损害那样的复杂并发症。显然从而监视即时 RFA 过程优化肝的癌的治疗。

Biomarkers for predicting efficacy of chimeric antigen receptor T cell therapy and their detection methods

Cancer immunotherapy has emerged as the fourth most prevalent approach to tumor treatment,alongside surgery,radiotherapy,and chemotherapy.After several decades of development,chimeric antigen receptor T(CAR-T)cell therapy,a promising branch of adoptive T-cell therapy,has demonstrated superior efficacy and safety in comparison to other cell therapies in the treatment of cancer.At present,CAR-T cells are predominantly used to treat hematological malignancies,although their application in solid tumors is being readily investigated.Although numerous studies have examined the biomarkers associated with the safety of CAR-T cell therapy,few have evaluated predictors of CAR-T cell therapeutic efficacy.Thus,the primary objective of this review article was to provide a comprehensive overview of the factors predicting the efficacy of CAR-T cell therapy,with a particular focus on biomarkers and their detection methods.

Generation and application of patient-derived xenograft models in pancreatic cancer research

Objective:Pancreatic ductal adenocarcinoma cancer(PDAC)is one of the leading causes of cancer-related death worldwide.Hence,the development of effective anti-PDAC therapies is urgently required.Patient-derived xenograft(PDX)models are useful models for developing anti-cancer therapies and screening drugs for pre&sion medicine.This review aimed to provide an updated summary of using PDX models in PDAC.Data sources:The author retrieved information from the PubMed database up to June 2019 using various combinations of search terms,including PDAC,pancreatic carcinoma,pancreatic cancer,patient-derived xenografts or PDX,and patient-derived tumor xenografts or PDTX.Study selection:Original articles and review articles relevant to the review's theme were selected.Results:PDX models are better than cell line-derived xenograft and other models.PDX models consistently demonstrate retained tumor morphology and genetic stability,are benefi&al in cancer research,could enhance drug discovery and oncologic mechanism development of PDAC,allow an improved understanding of human cancer cell biology,and help guide personalized treatmem.Conclusions:In this review,we outline the status and application of PDX models in both basic and pre-clinical pancreatic cancer researches.PDX model is one of the most appropriate pre-clinical tools that can improve the prognosis of patients with pancreatic cancer in the future.

The current surgical treatment of pancreatic neuroendocrine neoplasms in China: a national wide cross-sectional study

Objective:The aim of this study is to investigate the current status of the diagnosis and treatment of patients with pancreatic neuroendocrine neoplasms(pNENs)undergoing surgery in China.Methods:This is a multicenter cross-sectional study performed in China.Data from patients with pNENs undergoing surgery at 33 high-volume medical centers,where the number of pancreatectomies exceeds 20 cases per year,were collected and analyzed between March 1,2016 and February 28,2017.Results:In total,392 patients with pNENs were enrolled.The male to female ratio was 1.4.The majority of patients were aged between 40 and 70 years.65.6%of the patients had non-functional tumors.Among those with functional tumors,the percentages of insulinomas,gastrinomas,glucagonomas,and vasoactive intestinal peptide-secreting tumors were 94.8%,1.5%,2.2%,and 1.5%,respectively.Multidisciplinary team(MDT)discussion was conducted for 39.0%of the patients.Minimally invasive surgery was performed on 31.1%of the 392 patients.The incidence of grade B/C pancreatic fistula formation was 4.4%.A total of 89.0%of the surgeries achieved R0 resection,and 41.6%of the tumors were well differentiated.Lymph node metastasis was present in 8.9%of the patients.The percentages of patients with grades G1,G2,and G3 disease were 49.2%,45.7%,and 5.1%,respectively.Conclusion:This multicenter cross-sectional study systematically presents the current status of the diagnosis and treatment of patients with pNENs undergoing surgery in China.MDT consultation for pNENs has not been widely implemented in China.Although the incidence of surgical complications is relatively low,minimally invasive procedures should be further promoted.This study shows us how to improve the outcomes of these patients.

The current surgical treatment of pancreatic cancer in China: a national wide cross-sectional study

Objective: The aim of this study is to investigate the current status of pancreatic cancer patients undoing surgical treatment in China and to find ways to improve the survival of these patients in the future. Methods: This study is a national, multicenter, cross-sectional study in China. Information regarding pancreatic cancer patients undergoing surgical treatment from 34 high-volume tertiary IIIA level hospitals was collected and analyzed from the March 1, 2016 to the February 28, 2017. Results: In total, 2200 pancreatic cancer patients were enrolled from 34 tertiary IIIA level hospitals in 16 provinces across China. The male-to-female ratio was 1.5. More than 80% of the patients were between 50 and 70 years old. The top 4 symptoms were epigastric discomfort, abdominal pain, jaundice, and weight loss. Carbohydrate antigen 19-9 and carcinoembryonic antigen were elevated in 70.9% and 27.1% of patients, respectively. A multidisciplinary team (MDT) discussion was carried out for 35.0% of patients before surgery. The proportion of minimally invasive pancreatic surgeries was approximately 20%. A total of 83.4% of the operations achieved R0 resection, and the incidence of grade 3/4 postoperative complications was 7.7%. Only 13.4% of the patients received postoperative adjuvant chemotherapy. The percentage of pathological stage I tumors was only 24.5%. Conclusion: The majority of pancreatic cancer patients undergoing surgical resection in China are in an advanced stage. The MDT consultations for pancreatic cancer have not been widely carried out. R0 resection has been achieved in most cases, with relatively low incidence of serious complications, but minimally invasive pancreatic surgery should be further promoted. The application of postoperative chemotherapy remains low. This national, multicentre, cross-sectional study comprehensively presents the current status of pancreatic cancer patients undergoing surgical treatment and shows the road to improve survival of these patients in the future.

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.