Hepatocellular carcinoma recurrence after liver transplant:An Australian single-centre study

BACKGROUND Hepatocellular carcinoma(HCC)is a leading cause of cancer-related deaths worldwide.Liver transplantation(LT)offers the most effective treatment.HCC recurrence is the strongest risk factor that decreases post-LT survival in patients transplanted for HCC.The rate of HCC recurrence is generally reported as 8%-20%in the literature.Many predictors of HCC have already been researched,however,to our knowledge there are no published studies on this topic using Australian data.AIM To determine the rate and identify predictors of HCC recurrence in a contemporary Western Australian LT cohort.METHODS We performed a retrospective cohort study of all liver transplants in patients with HCC at Sir Charles Gairdner Hospital between 2006 and 2021.Data was collected from various health record databases and included recipient demographics,serum biochemistry,radiology,operation notes,explant histopathology and details of recurrence.Overall survival of HCC patients post-LT,stratified for recurrence,was calculated by Kaplan Meier analysis.Univariate and multivariate Cox regression was used to determine predictors of HCC recurrence post-LT.RESULTS Between 1/1/2006 and 12/31/2021,119 patients were transplanted with HCC.8.4%of subjects developed recurrent HCC after LT with median follow-up time of 5.4 years.The median time to recurrence was 2.9 years±0.75 years.When comparing baseline characteristics,a greater proportion of subjects with recurrence had common characteristics on explant histopathology,including>3 viable nodules(P=0.001),vascular invasion(P=0.003)and poorly differentiated HCC(P=0.03).Unadjusted survival curves showed lower 1-year,3-year,5-year and 10-year survival rates in subjects with HCC recurrence compared to those without HCC recurrence(90%vs 92%,70%vs 88%,42%vs 80%,14%vs 76%,respectively;log rank P<0.001).CONCLUSION HCC recurrence was low at 8.4%in this contemporary Australian cohort,however it significantly impacted post-LT survival.Further studies are required to confirm predictors of recurrence and improve recipient outcomes.

Leveraging machine learning for early recurrence prediction in hepatocellular carcinoma:A step towards precision medicine

The high rate of early recurrence in hepatocellular carcinoma(HCC)post curative surgical intervention poses a substantial clinical hurdle,impacting patient outcomes and complicating postoperative management.The advent of machine learning provides a unique opportunity to harness vast datasets,identifying subtle patterns and factors that elude conventional prognostic methods.Machine learning models,equipped with the ability to analyse intricate relationships within datasets,have shown promise in predicting outcomes in various medical disciplines.In the context of HCC,the application of machine learning to predict early recurrence holds potential for personalized postoperative care strategies.This editorial comments on the study carried out exploring the merits and efficacy of random survival forests(RSF)in identifying significant risk factors for recurrence,stratifying patients at low and high risk of HCC recurrence and comparing this to traditional COX proportional hazard models(CPH).In doing so,the study demonstrated that the RSF models are superior to traditional CPH models in predicting recurrence of HCC and represent a giant leap towards precision medicine.

From prediction to prevention:Machine learning revolutionizes hepatocellular carcinoma recurrence monitoring

In this editorial,we comment on the article by Zhang et al entitled Development of a machine learning-based model for predicting the risk of early postoperative recurrence of hepatocellular carcinoma.Hepatocellular carcinoma(HCC),which is characterized by high incidence and mortality rates,remains a major global health challenge primarily due to the critical issue of postoperative recurrence.Early recurrence,defined as recurrence that occurs within 2 years posttreatment,is linked to the hidden spread of the primary tumor and significantly impacts patient survival.Traditional predictive factors,including both patient-and treatment-related factors,have limited predictive ability with respect to HCC recurrence.The integration of machine learning algorithms is fueled by the exponential growth of computational power and has revolutionized HCC research.The study by Zhang et al demonstrated the use of a groundbreaking preoperative prediction model for early postoperative HCC recurrence.Challenges persist,including sample size constraints,issues with handling data,and the need for further validation and interpretability.This study emphasizes the need for collaborative efforts,multicenter studies and comparative analyses to validate and refine the model.Overcoming these challenges and exploring innovative approaches,such as multi-omics integration,will enhance personalized oncology care.This study marks a significant stride toward precise,efficient,and personalized oncology practices,thus offering hope for improved patient outcomes in the field of HCC treatment.

Computed tomography-based radiomics to predict early recurrence of hepatocellular carcinoma post-hepatectomy in patients background on cirrhosis

BACKGROUND The prognosis for hepatocellular carcinoma(HCC)in the presence of cirrhosis is unfavourable,primarily attributable to the high incidence of recurrence.AIM To develop a machine learning model for predicting early recurrence(ER)of posthepatectomy HCC in patients with cirrhosis and to stratify patients’overall survival(OS)based on the predicted risk of recurrence.METHODS In this retrospective study,214 HCC patients with cirrhosis who underwent curative hepatectomy were examined.Radiomics feature selection was conducted using the least absolute shrinkage and selection operator and recursive feature elimination methods.Clinical-radiologic features were selected through univariate and multivariate logistic regression analyses.Five machine learning methods were used for model comparison,aiming to identify the optimal model.The model’s performance was evaluated using the receiver operating characteristic curve[area under the curve(AUC)],calibration,and decision curve analysis.Additionally,the Kaplan-Meier(K-M)curve was used to evaluate the stratification effect of the model on patient OS.RESULTS Within this study,the most effective predictive performance for ER of post-hepatectomy HCC in the background of cirrhosis was demonstrated by a model that integrated radiomics features and clinical-radiologic features.In the training cohort,this model attained an AUC of 0.844,while in the validation cohort,it achieved a value of 0.790.The K-M curves illustrated that the combined model not only facilitated risk stratification but also exhibited significant discriminatory ability concerning patients’OS.CONCLUSION The combined model,integrating both radiomics and clinical-radiologic characteristics,exhibited excellent performance in HCC with cirrhosis.The K-M curves assessing OS revealed statistically significant differences.

Recurrence scoring system predicting early recurrence for patients with pancreatic ductal adenocarcinoma undergoing pancreatectomy and portomesenteric vein resection

BACKGROUND Pancreatectomy with concomitant portomesenteric vein resection(PVR)enables patients with portomesenteric vein(PV)involvement to achieve radical resection of pancreatic ductal adenocarcinoma,however,early recurrence(ER)is frequently observed.AIM To predict ER and identify patients at high risk of ER for individualized therapy.METHODS Totally 238 patients undergoing pancreatectomy and PVR were retrospectively enrolled and were allocated to the training or validating cohort.Univariate Cox and LASSO regression analyses were performed to construct serum recurrence score(SRS)based on 26 serum-derived parameters.Uni-and multivariate Cox regression analyses of SRS and 18 clinicopathological variables were performed to establish a Nomogram.Receiver operating characteristic curve analysis was used to evaluate the predictive accuracy.Survival analysis was performed using Kaplan-Meier method and log-rank test.RESULTS Independent serum-derived recurrence-relevant factors of LASSO regression model,including postoperative carbohydrate antigen 19-9,postoperative carcinoembryonic antigen,postoperative carbohydrate antigen 125,preoperative albumin(ALB),preoperative platelet to ALB ratio,and postoperative platelets to lymphocytes ratio,were used to construct SRS[area under the curve(AUC):0.855,95%CI:0.786–0.924].Independent risk factors of recurrence,including SRS[hazard ratio(HR):1.688,95%CI:1.075-2.652],pain(HR:1.653,95%CI:1.052-2.598),perineural invasion(HR:2.070,95%CI:0.827-5.182),and PV invasion(HR:1.603,95%CI:1.063-2.417),were used to establish the recurrence nomogram(AUC:0.869,95%CI:0.803-0.934).Patients with either SRS>0.53 or recurrence nomogram score>4.23 were considered at high risk for ER,and had poor long-term outcomes.CONCLUSION The recurrence scoring system unique for pancreatectomy and PVR,will help clinicians in predicting recurrence efficiently and identifying patients at high risk of ER for individualized therapy.

Postoperative serum tumor markers-based nomogram predicting early recurrence for patients undergoing radical resections of pancreatic ductal adenocarcinoma

BACKGROUND Early recurrence(ER)is associated with dismal outcomes in patients undergoing radical resection for pancreatic ductal adenocarcinoma(PDAC).Approaches for predicting ER will help clinicians in implementing individualized adjuvant therapies.Postoperative serum tumor markers(STMs)are indicators of tumor progression and may improve current systems for predicting ER.AIM To establish an improved nomogram based on postoperative STMs to predict ER in PDAC.METHODS We retrospectively enrolled 282 patients who underwent radical resection for PDAC at our institute between 2019 and 2021.Univariate and multivariate Cox regression analyses of variables with or without postoperative STMs,were performed to identify independent risk factors for ER.A nomogram was constructed based on the independent postoperative STMs.Receiver operating characteristic curve analysis was used to evaluate the area under the curve(AUC)of the nomogram.Survival analysis was performed using Kaplan-Meier survival plot and log-rank test.RESULTS Postoperative carbohydrate antigen 19-9 and carcinoembryonic antigen levels,preoperative carbohydrate antigen 125 levels,perineural invasion,and pTNM stage III were independent risk factors for ER in PDAC.The postoperative STMs-based nomogram(AUC:0.774,95%CI:0.713-0.835)had superior accuracy in predicting ER compared with the nomogram without postoperative STMs(AUC:0.688,95%CI:0.625-0.750)(P=0.016).Patients with a recurrence nomogram score(RNS)>1.56 were at high risk for ER,and had significantly poorer recurrence-free survival[median:3.08 months,interquartile range(IQR):1.80-8.15]than those with RNS≤1.56(14.00 months,IQR:6.67-24.80),P<0.001).CONCLUSION The postoperative STMs-based nomogram improves the predictive accuracy of ER in PDAC,stratifies the risk of ER,and identifies patients at high risk of ER for tailored adjuvant therapies.

Assessing recent recurrence after hepatectomy for hepatitis Brelated hepatocellular carcinoma by a predictive model based on sarcopenia

BACKGROUND Sarcopenia may be associated with hepatocellular carcinoma(HCC)following hepatectomy.But traditional single clinical variables are still insufficient to predict recurrence.We still lack effective prediction models for recent recurrence(time to recurrence<2 years)after hepatectomy for HCC.AIM To establish an interventable prediction model to estimate recurrence-free survival(RFS)after hepatectomy for HCC based on sarcopenia.METHODS We retrospectively analyzed 283 hepatitis B-related HCC patients who underwent curative hepatectomy for the first time,and the skeletal muscle index at the third lumbar spine was measured by preoperative computed tomography.94 of these patients were enrolled for external validation.Cox multivariate analysis was per-formed to identify the risk factors of postoperative recurrence in training cohort.A nomogram model was developed to predict the RFS of HCC patients,and its predictive performance was validated.The predictive efficacy of this model was evaluated using the receiver operating characteristic curve.RESULTS Multivariate analysis showed that sarcopenia[Hazard ratio(HR)=1.767,95%CI:1.166-2.678,P<0.05],alpha-fetoprotein≥40 ng/mL(HR=1.984,95%CI:1.307-3.011,P<0.05),the maximum diameter of tumor>5 cm(HR=2.222,95%CI:1.285-3.842,P<0.05),and hepatitis B virus DNA level≥2000 IU/mL(HR=2.1,95%CI:1.407-3.135,P<0.05)were independent risk factors associated with postoperative recurrence of HCC.Based on the sarcopenia to assess the RFS model of hepatectomy with hepatitis B-related liver cancer disease(SAMD)was established combined with other the above risk factors.The area under the curve of the SAMD model was 0.782(95%CI:0.705-0.858)in the training cohort(sensitivity 81%,specificity 63%)and 0.773(95%CI:0.707-0.838)in the validation cohort.Besides,a SAMD score≥110 was better to distinguish the high-risk group of postoperative recurrence of HCC.CONCLUSION Sarcopenia is associated with recent recurrence after hepatectomy for hepatitis B-related HCC.A nutritional status-based prediction model is first established for postoperative recurrence of hepatitis B-related HCC,which is superior to other models and contributes to prognosis prediction.

Pre-operative enhanced magnetic resonance imaging combined with clinical features predict early recurrence of hepatocellular carcinoma after radical resection

BACKGROUND Indentifying predictive factors for postoperative recurrence of hepatocellular carcinoma(HCC)has great significance for patient prognosis.AIM To explore the value of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid(Gd-EOB-DTPA)enhanced magnetic resonance imaging(MRI)combined with clinical features in predicting early recurrence of HCC after resection.METHODS A total of 161 patients with pathologically confirmed HCC were enrolled.The patients were divided into early recurrence and non-early recurrence group based on the follow-up results.The clinical,laboratory,pathological results and Gd-EOB-DTPA enhanced MRI imaging features were analyzed.RESULTS Of 161 patients,73 had early recurrence and 88 were had non-early recurrence.Univariate analysis showed that patient age,gender,serum alpha-fetoprotein level,the Barcelona Clinic Liver Cancer stage,China liver cancer(CNLC)stage,microvascular invasion(MVI),pathological satellite focus,tumor size,tumor number,tumor boundary,tumor capsule,intratumoral necrosis,portal vein tumor thrombus,large vessel invasion,nonperipheral washout,peritumoral enhancement,hepatobiliary phase(HBP)/tumor signal intensity(SI)/peritumoral SI,HBP peritumoral low signal and peritumoral delay enhancement were significantly associated with early recurrence of HCC after operation.Multivariate logistic regression analysis showed that patient age,MVI,CNLC stage,tumor boundary and large vessel invasion were independent predictive factors.External data validation indicated that the area under the curve of the combined predictors was 0.861,suggesting that multivariate logistic regression was a reasonable predictive model for early recurrence of HCC.CONCLUSION Gd-EOB-DTPA enhanced MRI combined with clinical features would help predicting the early recurrence of HCC after operation.

SIMAP500: A novel risk score to identify recipients at higher risk of hepatocellular carcinoma recurrence following liver transplantation

BACKGROUND Recurrence of hepatocellular carcinoma(HCC)following liver transplantation(LT)has a devastating influence on recipients’survival;however,the risk of recur-rence is not routinely stratified.Risk stratification is vital with a long LT waiting time,as that could influence the recurrence despite strict listing criteria.AIM This study aims to identify predictors of recurrence and develop a novel risk pre-diction score to forecast HCC recurrence following LT.METHODS A retrospective review of LT for HCC recipients at University Hospitals Bir-mingham between July 2011 and February 2020.Univariate and multivariate analyses were performed to identify recurrence predictors,based on which the novel SIMAP500(satellite nodules,increase in size,microvascular invasion,AFP>500,poor differentiation)risk score was proposed.RESULTS 234 LTs for HCC were performed with a median follow-up of 5.3 years.Recurrence developed in 25 patients(10.7%).On univariate analyses,RETREAT score>3,α-fetoprotein(AFP)at listing 100-500 and>500,bridging,increased tumour size between imaging at the listing time and explant histology,increase in the size of viable tumour between listing and explant,presence of satellite nodules,micro-and macrovascular invasion on explant and poor differentiation of tumours were significantly associated with recurrence,based on which,the SIMAP500 risk score is proposed.The SIMAP500 demonstrated an excellent predictive ability(c-index=0.803)and outper-formed the RETREAT score(c-index=0.73).SIMAP500 is indicative of the time to disease recurrence.CONCLUSION SIMAP500 risk score identifies the LT recipients at risk of HCC recurrence.Risk stratification allows patient-centric post-transplant surveillance programs.Further validation of the score is recommended.

Challenges related to clinical decision-making in hepatocellular carcinoma recurrence post-liver transplantation: Is there a hope?

Hepatocellular carcinoma(HCC)is a common liver malignancy and represents a serious cause of cancer-related mortality and morbidity.One of the favourable curative surgical therapeutic options for HCC is liver transplantation(LT)in selected patients fulfilling the known standard Milan/University of California San Francisco criteria which have shown better outcomes and longer-term survival.Despite careful adherence to the strict HCC selection criteria for LT in different transplant centres,the recurrence rate still occurs which could negatively affect HCC patients’survival.Hence HCC recurrence post-LT could predict patients’survival and prognosis,depending on the exact timing of recurrence after LT(early or late),and whether intra/extrahepatic HCC recurrence.Several factors may aid in such a complication,particularly tumour-related criteria including larger sizes,higher grades or poor tumour differentiation,microvascular invasion,and elevated serum alpha-fetoprotein.Therefore,managing such cases is challenging,different therapeutic options have been proposed,including curative surgical and ablative treatments that have shown better outcomes,compared to the palliative locoregional and systemic therapies,which may be helpful in those with unresectable tumour burden.To handle all these issues in our review.

Toripalimab in combination with chemotherapy effectively suppresses local recurrence and metastatic sarcomatoid renal cell carcinoma:A case report

BACKGROUND Sarcomatoid renal cell carcinoma(SRCC)is a rare variant of renal cell carcinoma associated with an unfavorable prognosis.The efficacy of conventional chemo-therapy and targeted therapies are limited,whereas the emergence of immune checkpoint inhibitor has introduced new avenues for managing advanced SRCC.CASE SUMMARY A 77-year-old female patient was referred to our hospital following the incidental detection of a right kidney tumor without specific symptoms.The tumor was successfully resected,and subsequent pathological examination confirmed SRCC.She experienced both local recurrence and distant metastasis eight months after the initial laparoscopic resection.Following six cycles of toripalimab combined with pirarubicin chemotherapy,the patient achieved a partial response.Subse-quently,the patient attained an almost-complete continuous response to toripa-limab monotherapy maintenance for an additional six cycles.She has not experienced disease progression for 15 months,and her overall survival has reached 24 months thus far.CONCLUSION Combination therapy with programmed death 1 antibodies and cytotoxic agents may be a recommended first-line treatment approach for SRCC.

Predictors of early and late hepatocellular carcinoma recurrence

Hepatocellular carcinoma(HCC)is the most frequent liver neoplasm,and its incidence rates are constantly increasing.Despite the availability of potentially curative treatments(liver transplantation,surgical resection,thermal ablation),long-term outcomes are affected by a high recurrence rate(up to 70%of cases 5 years after treatment).HCC recurrence within 2 years of treatment is defined as“early”and is generally caused by the occult intrahepatic spread of the primary neoplasm and related to the tumor burden.A recurrence that occurs after 2 years of treatment is defined as“late”and is related to de novo HCC,independent of the primary neoplasm.Early HCC recurrence has a significantly poorer prognosis and outcome than late recurrence.Different pathogenesis corresponds to different predictors of the risk of early or late recurrence.An adequate knowledge of predictive factors and recurrence risk stratification guides the therapeutic strategy and post-treatment surveillance.Patients at high risk of HCC recurrence should be referred to treatments with the lowest recurrence rate and when standardized to combined or adjuvant therapy regimens.This review aimed to expose the recurrence predictors and examine the differences between predictors of early and late recurrence.

Imaging-based prediction of hepatocellular carcinoma recurrence after microwave ablation as bridge therapy: A glimpse into the future

Liver transplantation(LT)remains the treatment of choice for early-stage hepato-cellular carcinoma(HCC)and offers the best long-term oncological outcomes.However,the increasing waiting list for LT has led to a significant dropout rate as patients experience tumor progression beyond the Milan criteria.Currently,locoregional therapies,such as microwave ablation(MWA),have emerged as promising bridge treatments for patients awaiting LT.These therapies have shown promising results in preventing tumor progression,thus reducing the dropout rate of LT candidates.Despite the efficacy of MWA in treating HCC,tumoral recurrence after ablation remains a major challenge and significantly impacts the prognosis of HCC patients.Therefore,accurately diagnosing tumoral recurrence post-ablation is crucial.Recent studies have developed novel imaging features based on magnetic resonance imaging of HCC,which could provide essential information for predicting early tumoral recurrence after MWA.These advancements could address this unresolved challenge,improving the clinical outcomes of patients on the LT waiting list.This article explored the current landscape of MWA as a bridge therapy for HCC within the Milan criteria,high-lighting the emerging role of novel imaging-based features aimed at improving the prediction of tumor recurrence after MWA.

Finding the seed of recurrence:Hepatocellular carcinoma circulating tumor cells and their potential to drive the surgical treatment

The treatment for hepatocellular carcinoma(HCC)relies on liver resection,which is,however,burdened by a high rate of recurrence after surgery,up to 60%at 5 years.No pre-operative tools are currently available to assess the recurrence risk tailored to every single patient.Recently liquid biopsy has shown interesting results in diagnosis,prognosis and treatment allocation strategies in other types of cancers,since its ability to identify circulating tumor cells(CTCs)derived from the primary tumor.Those cells were advocated to be responsible for the majority of cases of recurrence and cancer-related deaths for HCC.In fact,after being modified by the epithelial-mesenchymal transition,CTCs circulate as“seeds”in peripheral blood,then reach the target organ as dormant cells which could be subsequently“awakened”and activated,and then initiate metastasis.Their presence may justify the disagreement registered in terms of efficacy of anatomic vs non-anatomic resections,particularly in the case of microvascular invasion,which has been recently pointed as a histological sign of the spread of those cells.Thus,their presence,also in the early stages,may justify the recurrence event also in the contest of liver transplant.Understanding the mechanism behind the tumor progression may allow improving the treatment selection according to the biological patient-based characteristics.Moreover,it may drive the development of novel biological tailored tests which could address a specific patient to neoadjuvant or adjuvant strategies,and in perspective,it could also become a new method to allocate organs for transplantation,according to the risk of relapse after liver transplant.The present paper will describe the most recent evidence on the role of CTCs in determining the relapse of HCC,highlighting their potential clinical implication as novel tumor behavior biomarkers able to influence the surgical choice.

Risk factors associated with early and late recurrence after curative resection of hepatocellular carcinoma: a single institution's experience with 398 consecutive patients

BACKGROUND: Surgical resection is an important curative treatment for hepatocellular carcinoma (HCC); however, some patients experience an unexpected recurrence even after hepatectomy. The present study aimed to investigate risk factors and predictive criteria for early and late recurrence of HCC after resection.METHODS: A retrospective analysis of 398 Chinese patients who received curative resection for HCC was conducted. Patients were divided into three groups: without recurrence, early recurrence and late recurrence. Prognostic factors and predictive criteria for early and late recurrence were statistically analyzed. RESULTS: The cumulative recurrence-free survival rates at1, 2, 3, 4, and 5 years were 75.5%, 58.2%, 54.1%, 40.5%, and28.7%, respectively. The distribution of the time to recurrence suggested that recurrence could be divided into early phase(before 2 years; n=164) and late phase (after 2 years; n=83)Cox’s multivariate proportional hazard model analysis revealed that multiplicity of tumors (P=0.004) and venous infiltration(P=0.002) were independent risk factors associated with early recurrence. In contrast, indocyanine green retention rate at 15minutes (P=0.007), serum albumin level (P=0.045), and HBeAg status ( =0.028) proved to be significant independent adverse prognostic factors for late recurrence. Patients with at least 1of the 2 early recurrence risk factors (multiplicity of tumors ≥2and venous infiltration) or with 2 or more late recurrence risk factors are often susceptible to recurrence (P=1.36e-4 and 1.0e-6respectively).CONCLUSIONS: Early and late recurrences correlate with different risk factors and predictive criteria. Early recurrence primarily results from intrahepatic metastases, while late recurrence may be multicentric in origin.

Patients with early recurrence of hepatocellular carcinoma have poor prognosis

BACKGROUND： Early recurrence （ER） after hepatic resection （HR） is a poor prognostic factor for patients with hepatocellular carcinoma （HCC）. This study aimed to identify the clinico- pathological features, outcomes, and risk factors for ER after HR for small HCC in order to clarify the reasons why ER is a worse recurrence pattern. METHODS： We retrospectively examined 130 patients who underwent HR for small HCC （___30 mm）. Recurrence was clas- sifted into ER （〈2 years） and late recurrence （LR） （_〉2 years）. The clinicopathological features, outcomes, and risk factors for ER were analyzed by multivariate analysis. RESULTS： ER was observed in 39 patients （30.0%）. The sur- vival rate of the ER group was significantly lower than that of the LR group （P〈0.005）, and ER was an independent prognos- tic factor for poor survival （P=0.0001）. The ER group had a significantly higher frequency （P=0.0039） and shorter interval （P=0.027） of development to carcinoma beyond the Milan criteria （DBMC） compared with the LR group, and ER was an independent risk factor for DBMC （P〈0.0001）. Multi-nodularity, non-simple nodular type, and microvascular invasion were independent predictors for ER （P=0.012, 0.010, and 0.019, respectively）.CONCLUSIONS： ER was a highly malignant recurrence pattern associated with DBMC and subsequent poor survival after HR for small HCC. Multi-nodularity, non-simple nodular type, and microvascular invasion predict ER, and taking these factors into consideration may be useful for the decision of the treatment strategy for small HCC after HR.

Risk factors for immediate post-operative fatal recurrence after curative resection of hepatocellular carcinoma

AIM： To investigate the clinicopathological risk factors for immediate post-operative fatal recurrence of hepatocellular carcinoma （HCC）, which may have practical implication and contribute to establishing high risk patients for pre- or post-operative preventive measures against HCC recurrence. METHODS： From June 1994 to May 2004, 269 patients who received curative resection for HCC were reviewed. Of these patients, those who demonstrated diffuse intrahepatic or multiple systemic recurrent lesions within 6 mo after surgery were investigated （fatal recurrence group）. The remaining patients were designated as the control group, and the two groups were compared for clinicopathologic risk factors. RESULTS： Among the 269 patients reviewed, 30 patients were enrolled in the fatal recurrence group. Among the latter, 20 patients showed diffuse intrahepatic recurrence type and 10 showed multiple systemic recurrence type. Multivariate analysis between the fatal recurrence group and control group showed that preoperative serum alpha-fetoprotein （AFP） level was greater than 1 000 μg/L （P= 0.02; odds ratio = 2.98）, tumor size greater than 6.5 cm （P= 0.03; OR= 2.98）, and presence of microvascular invasion （P= 0.01; OR=4.89） were the risk factors in the fatal recurrence group. The 48.1% of the patients who had all the three risk factors and the 220 of those who had two risk factors experienced fatal recurrence within 6 mo after surgery. CONCLUSION： Three distinct risk factors for immediate post-operative fatal recurrence of HCC after curative resection are pre-operative serum AFP level 〉 1 000 μg/L,tumor size〉6.5 cm, and microvascular invasion. The high risk patients with two or more risk factors should be the candidates for various adjuvant clinical trials.

Adjuvant heparanase inhibitor PI-88 therapy for hepatocellular carcinoma recurrence

AIM: To demonstrate that administering heparanase inhibitor PI-88 at 160 mg/d is safe and promising in reducing hepatocellular carcinoma (HCC) recurrence for up to 3 year following curative resection.

Local recurrence is an important prognostic factor of hepatocellular carcinoma

AIM： To clarify the importance of complete treatment by PELT. METHODS： A total of 140 previously untreated cases of HCC were enrolled in this study from 1988 to 2002. The inclusion criteria were： a solitary tumor less than 4 cm in diameter or multiple tumors, fewer than four in number and less than 3 cm in diameter, without extrahepatic metastasis or vessel invasion. As general principles for the treatment of HCC, the patients underwent transcatheter arterial chemoembolization （TACE） prior to PEIT. After the initial treatment of the patients, ultrasonography and computed tomography were performed, and measurement of serum levels of α- fetoprotein （AFP） was determined. When tumor recurrences were detected, PEIT and/or TACE were repeated whenever the hepatic functional reserve of the patient permitted. We then analyzed the variables that could influence prognosis, including tumor size and number, the serum levels of AFP, the parameters of hepatic function （albumin, bilirubin, ALT, hepaplastin test, platelet number, and indocyanine green retention at 15 rain [ICG-R15]）, combined therapy with TACE, distant recurrence, and local recurrence. RESULTS： Univariate analysis identified the ICG test, serum levels of AFP and albumin, tumor size and number, and local recurrence, but not distant recurrence, as significant prognostic variables. In multivariate analysis using those five parameters, the ICG test, tumor size, tumor number, and local recurrence were identified as significant prognostic factors. In both univariate and multivariate analyses, the relative risk for the ICG test was the highest, followed by local recurrence. CONCLUSION： We found that local recurrence is an independent prognostic factor of HCC, indicating that achieving complete treatment for HCC on first treatment is important for improving the prognosis of patients with HCC. 2005 The WJG Press and Elsevier Inc. All rights reserved.

Preoperative serum liver enzyme markers for predicting early recurrence after curative resection of hepatocellular carcinoma

BACKGROUND：Early recurrence of hepatocellular carcinoma（HCC）is associated with worse prognosis after liver resection This study aimed to investigate the prognostic value of com mon liver enzyme markers in HCC early recurrence after cu rative hepatectomy and to establish a simple predictive model for HCC early recurrence.METHODS： A total of 200 patients who had undergone curative resection for HCC were retrospectively analyzed. The patients were divided into early recurrence （within 2 years） and non-early recurrence groups. Demographical characteristics, preopera- tive liver function parameters, surgical factors and tumor related factors of the patients were assessed by univariate analysis to identify potential significant predictors for early recurrence after resection of HCC. Parameters with statisti- cal significance were entered into a Cox proportional hazard model to find independent risk factors. Receiver operating characteristic analysis was done to determine optimal cut-off values and the number of combined factors in multi-factor predictive model. RESULTS： Of 13 potential risk factors for early recurrence identified by univariate analysis, high lactate dehydrogenase （LDH〉206 U/L, HR=1.711, P=0.006）, high aspartate aminotransferase （AST）/alanine aminotransferase （ALT） ratio （AST/ ALT〉0.96, HR=1.769, P=0.006）, elevated alpha-fetoprotein （AFP〉8.6 ng/mL, HR=2.079, P=0.007）, small resection margin （〈1 cm, HR=2.354, P〈0.001） and advanced TNM stage （TNM III-IV, HR=2.164, P〈0.001） were independent risk factors for early recurrence of HCC shown by multivariate analysis. Patients with three or more concurrent independent risk factors had significantly higher risk for early recurrence than those with low risk factors. The sensitivity and specificity of this predictive model are 53.6% and 80.7%, respectively （area under curve=0.741, 95% CI 0.674-0.800, P〈0.0001）. CONCLUSIONS： Preoperative common fiver enzyme markers, LDH and AST/ALT ratio, were independently associated with early recurrence of HCC. The combination of serum liver enzyme markers with AFP, resection margin and TNM stage bet- ter predicted early recurrence of HCC after curative resection in a simple multi-factor model.