Prognosis of hepatocellular carcinoma with bile duct tumor thrombus after R0 resection:a matched study

BACKGROUND: Hepatocellular carcinoma (HCC) with bile duct tumor thrombus (BDTT) is rare. The present study aimed to determine post-surgical prognoses in HCC patients with BDTT, as outcomes are currently unclear.
METHODS: We compared the prognoses of 110 HCC patients without BDTT (group A) to 22 cases with BDTT (group B). The two groups were matched in age, gender, tumor etiology, size, number, portal vascular invasion, and TNM stage. Addi-tionally, 28 HCC patients with BDTT were analyzed to identify prognostic risk factors.
RESULTS: The 1-, 3-, and 5-year overall survival rates were 90.9%, 66.9%, and 55.9% for group A and 81.8%, 50.0%, and 37.5% for group B, respectively. The median survival time in groups A and B was 68.8 and 31.4 months, respectively (P=0.043). The patients for group B showed higher levels of serum total bilirubin, alanine aminotransferase and gamma-glutamyl transferase, a larger hepatectomy range, and a higher rate of anatomical resection. In subgroup analyses of patients with BDTT who underwent R0 resection, TNM stage III-IV was an independent risk factor for overall survival; these patients had worse prognoses than those with TNM stage I-II after R0 resection (hazard ratio=6.056,P=0.014). Besides, univariate and multivariate analyses revealed that non-R0 resection and TNM stage III-IV were independent risk fac-tors for both disease-free survival and overall survival of 28 HCC patients with BDTT. The median overall survival time of patients with BDTT who underwent R0 resection was longer than that of patients who did not undergo R0 resection (31.0 vs 4.0 months,P=0.007).
CONCLUSIONS: R0 resection prolonged survival time in HCC patients with BDTT, although prognosis remains poor. For such patients, R0 resection is an important treatment that determines long-term survival.     

Liver transplantation for hepatocellular carcinoma on cirrhosis: strategies to avoid tumor recurrence

Hepatocellular carcinoma(HCC) is one of the most frequent neoplasms worldwide and in most cases it is associated with chronic liver disease.Liver transplantation(LT) is potentially the optimal treatment for those patients with HCC who have a poor functional hepatic reserve due to their underlying chronic liver disease.However,due to the limited availability of donors,only those patients whose oncologic profile is favorable can be considered for LT.Despite the careful selection of candidates based on strict ...     

Adjuvant sorafenib in hepatocellular carcinoma: A cautionary comment of STORM trial

Recurrence rate of hepatocellular carcinoma (HCC) is very high even after curative surgery, and no postoperative therapies have been definitively shown to prevent HCC recurrence. Sorafenib is proved to be effective for advanced HCC by two large randomized controlled trials in 2008 and 2009. Therefore it stands to reason to expect that adjuvant sorafenib may improve post-surgery outcomes of patients with HCC. However, many questions still exist about the value of sorafenib for patients with HCC after surgery or transarterial chemoembolization. In this editorial, we complehensively reviewed the safety and efficacy of adjuvant sorafenib for patients with hepatocellar carcinoma after surgery or transarterial chemoembolization. We emphasized the positive and negative role of sorafenib.     

R0 resection in the treatment of gastric cancer: Room for improvement

Gastric carcinoma is one of the most frequent malignancies in the world and its clinical behavior especially depends on the metastatic potential of the tumor.In particular,lymphatic metastasis is one of the main predictors of tumor recurrence and survival,and current pathological staging systems reflect the concept that lymphatic spread is the most relevant prognostic factor in patients undergoing curative resection.This is compounded by the observation that two-thirds of gastric cancer in the Western world...     

原发性肝碰撞瘤1例并文献复习

病例：患者男,62岁,农民,因“左上腹部包块伴隐痛不适1周余”,于2008年3月24日入院。隐痛呈持续性,无放射痛。翻身时可扪及左上腹部包块,无恶心、呕吐,无腹胀、腹泻,无畏寒、发热,无泛酸、嗳气,无心悸、乏力,无胸痛。入院查体：体温36．5℃,脉搏76次／min,血压110／65mmHg（1mmHg=0．133kPa）,呼吸18次／min。神清,精神萎,全身皮肤、黏膜和巩膜无黄染,     

Risk factors and surgical outcomes for spontaneous rupture of BCLC stages A and B hepatocellular carcinoma: A case-control study

AIM: To investigate the risk factors and surgical outcomes for spontaneous rupture of Barcelona Clinic Liver Cancer (BCLC) stages A and B hepatocellular carcinoma (HCC).METHODS: From April 2002 to November 2006, 92 consecutive patients with spontaneous rupture of BCLC stage A or B HCC undergoing hepatic resection were included in a case group. A control arm of 184 cases (1:2 ratio) was chosen by matching the age, sex, BCLC stage and time of admission among the 2904 consecutive patients with non-ruptured HCC undergoing hepatic resection. Histological confirmation of HCC was available for all patients and ruptured HCC was confirmed by focal discontinuity of the tumor with surrounding perihepatic hematoma observed intraoperatively. Patients with microvascular thrombus in the hepatic vein branches were excluded from the study. Clinical data and survival time were collected and analysed.RESULTS: Sixteen patients were excluded from the study based on exclusion criteria, of whom 3 were in the case group and 13 in the control group. Compared with the control group, more patients in the case group had underlying diseases of hypertension (10.1% vs 3.5%, P = 0.030) and liver cirrhosis (82.0% vs 57.9%, P < 0.001). Tumors in 67 (75.3%) patients in the case group were located in segments II, III and VI, and the figure in the control group was also 67 (39.7%) (P < 0.001). On multivariate analysis, hypertension (HR = 7.38, 95%CI: 1.91-28.58, P = 0.004), liver cirrhosis (HR = 6.04, 95%CI: 2.83-12.88, P < 0.001) and tumor location in segments II, III and VI (HR = 5.03, 95%CI: 2.70-6.37, P < 0.001) were predictive for spontaneous rupture of HCC. In the case group, the median survival time and median disease-free survival time were 12 mo (range: 1-78 mo) and 4 mo (range: 0-78 mo), respectively. The 1-, 3- and 5-year overall survival rates and disease-free survival rates were 66.3%, 23.4% and 10.1%, and 57.0%, 16.8% and 4.5%, respectively. Only radical resection remained predictive for overall survival (HR = 0.32, 95%CI: 0.08-0.61, P = 0.015) and disease-free survival (HR = 0.12, 95%CI: 0.01-0.73, P = 0.002).CONCLUSION: Tumor location, hypertension and liver cirrhosis are associated with spontaneous rupture of HCC. One-stage hepatectomy should be recommended to patients with BCLC stages A and B disease.     

Prognostic value of the preoperative fibrinogen-to-albumin ratio in pancreatic ductal adenocarcinoma patients undergoing R0 resection

BACKGROUNDInflammation plays an important role in tumor progression, and growing evidence has confirmed that the fibrinogen-to-albumin ratio (FAR) is an important prognostic factor for overall survival in malignant tumors.AIMTo investigate the prognostic significance of FAR in patients undergoing radical R0 resection of pancreatic ductal adenocarcinoma (PDAC).METHODSWe retrospectively analyzed the data of 282 patients with PDAC who underwent radical R0 resection at The Cancer Hospital of the Chinese Academy of Medical Sciences from January 2010 to December 2019. The surv_cutpoint function of the R package survminer via RStudio software (version 1.3.1073, http://www.rstudio.org) was used to determine the optimal cut-off values of biological markers, such as preoperative FAR. The Kaplan-Meier method and log-rank tests were used for univariate survival analysis, and a Cox regression model was used for multivariate survival analysis for PDAC patients who underwent radical R0 resection.RESULTSThe optimal cut-off value of FAR was 0.08 by the surv_cutpoint function. Higher preoperative FAR was significantly correlated with clinical symptoms (P = 0.001), tumor location (P < 0.001), surgical approaches (P < 0.001), preoperative plasma fibrinogen concentration (P < 0.001), and preoperative plasma albumin level (P < 0.001). Multivariate analysis showed that degree of tumor differentiation (P < 0.001), number of metastatic lymph nodes [hazard ratio (HR): 0.678, 95% confidence interval (CI): 0.509-0.904, P = 0.008], adjuvant therapy (HR: 1.604, 95%CI: 1.214-2.118, P = 0.001), preoperative cancer antigen 19-9 level (HR: 1.740, 95%CI: 1.288-2.352, P < 0.001), and preoperative FAR (HR: 2.258, 95%CI: 1.720-2.963, P < 0.001) were independent risk factors for poor prognosis in patients with PDAC who underwent radical R0 resection.CONCLUSIONThe increase in preoperative FAR was significantly related to poor prognosis in patients undergoing radical R0 resection for PDAC. Preoperative FAR can be used clinically to predict the prognosis of PDAC patients undergoing radical R0 resection.     

Association of HER2 status with prognosis in gastric cancer patients undergoing R0 resection: A large-scale multicenter study in China

AIM: To determine whether the positive status of human epidermal growth receptor 2(HER2) can be regarded as an effective prognostic factor for patients with gastric cancer(GC) undergoing R0 resection.METHODS: A total of 1562 GC patients treated by R0 resection were recruited. HER2 status was evaluated in surgically resected samples of all the patients using immunohistochemical(IHC) staining. Correlations between HER2 status and clinicopathological characteristics were retrospective analyzed. Hazard ratios(HRs) and 95% confidence intervals(CIs) were estimated using Cox proportional hazard model, stratified by age, gender, tumor location and tumor-nodemetastasis(TNM) stage, with additional adjustment for potential prognostic factors.RESULTS: Among 1562 patients, 548(positive rate = 35.08%, 95%CI: 32.72%-37.45%) were HER2 positive. Positive status of HER2 was significantly correlated with gender(P = 0.004), minority(P 0.001), tumor location(P = 0.001), pathological grade(P 0.001), TNM stage(P 0.001) and adjuvant radiotherapy(74.67% vs 23.53%, P = 0.011). No significant associations were observed between HER2 status and disease free survival(HR = 0.19, 95%CI: 0.96-1.46, P = 0.105) or overall survival(HR = 1.19, 95%CI: 0.96-1.48, P = 0.118) using multivariate analysis, although stratified analyses showed marginally statistically significant associations both in disease free survival and overall survival, especially among patients aged 60 years or with early TNM stages(Ⅰ and Ⅱ). Categorical age, TNM stage, neural invasion, and adjuvant chemotherapy were, as expected, independent prognostic factors for both disease free survival and overall survival. CONCLUSION: The positive status of HER2 based on IHC staining was not related to the survival in patients with GC among the Chinese population.     

Tumor microenvironment in primary liver tumors: A challenging role of natural killer cells

In the last years, several studies have been focused on elucidate the role of tumor microenvironment(TME) in cancer development and progression. Within TME, cells from adaptive and innate immune system are one of the main abundant components. The dynamic interactions between immune and cancer cells lead to the activation of complex molecular mechanisms that sustain tumor growth. This important cross-talk has been elucidate for several kind of tumors and occurs also in patients with liver cancer, such as hepatocellular carcinoma(HCC) and intrahepatic cholangiocarcinoma(iCCA). Liver is well-known to be an important immunological organ with unique microenvironment. Here, in normal conditions, the rich immune-infiltrating cells cooperate with non-parenchymal cells, such as liver sinusoidal endothelial cells and Kupffer cells, favoring self-tolerance against gut antigens. The presence of underling liver immunosuppressive microenvironment highlights the importance to dissect the interaction between HCC and iCCA cells with immune infiltrating cells, in order to understand how this cross-talk promotes tumor growth. Deeper attention is, in fact, focused on immune-based therapy for these tumors, as promising approach to counteract the intrinsic anti-tumor activity of this microenvironment. In this review, we will examine the key pathways underlying TME cell-cell communications, with deeper focus on the role of natural killer cells in primary liver tumors, such as HCC and iCCA, as new opportunities for immune-based therapeutic strategies.     

Therapeutic Results of Computed-Tomography-Guided Transcatheter Arterial Chemoembolization for Local Recurrence of Hepatocellular Carcinoma After Initial Transcatheter Arterial Chemoembolization: The Results of 85 Recurrent Tumors in 35 Patients

The aim of this study was to retrospectively evaluate the long-term results of transcatheter arterial chemoembolization (TACE) for the treatment of local recurrence of hepatocellular carcinoma (HCC) after the first TACE. Between September 1992 and October 2004, 85 recurrent HCC nodules of 35 patients were treated by TACE. During the median follow-up period of 15.5 months (range 1.9–58.6 months), 58 of the 85 treated tumors developed local recurrence again after the second TACE. The overall 6-, 12-, and 36-month recurrence-free rates of these tumors after the second TACE were 47.0%, 36.2%, and 25.8%, respectively. Local recurrence of HCC after the first TACE was treated by a second TACE with equivalent efficacy as that of the initial TACE, if segmental chemoembolization was achieved. We regard TACE as the treatment of choice for the management of local recurrence of HCC.     

Position paper of the Italian Association for the Study of the Liver (AISF): The multidisciplinary clinical approach to hepatocellular carcinoma

Patients with hepatocellular carcinoma should be managed with a multidisciplinary approach framed in a network where all the diagnostic techniques and therapeutic resources are available in order to provide the optimal level of care.Given this assumption, the Coordinating Committee of the Italian Association for the Study of the Liver nominated a panel of experts to elaborate practical recommendations for the multidisciplinary management of hepatocellular carcinoma aiming to provide: (1) homogeneous and efficacious diagnostic and staging work-up, and (2) the best treatment choice tailored to patient status and tumour stage at diagnosis.The 2010 updated American Association for the Study of Liver Disease Guidelines for hepatocellular carcinoma were selected as the reference document. For each management issue, the American Association for the Study of Liver Disease recommendations were briefly summarised and discussed, according to both the scientific evidence published after their release and the clinical expertise of the Italian centres taking care of these patients. The Italian Association for the Study of the Liver expert panel recommendations are finally reported.     

Liver transplantation for hepatocellular carcinoma beyond the Milan criteria: A review

Liver transplantation(LT) has been accepted as an effective therapy for hepatocellular carcinoma(HCC). The Milan criteria(MC) are widely used across the world to select LT candidates in HCC patients. However, the MC may be too strict because a substantial subset of patients who have HCC exceed the MC and who would benefit from LT may be unnecessarily excluded from the waiting list. In recent years, many extended criteria beyond the MC were raised, which were proved to be able to yield similar outcomes compared with those patients meeting the MC. Because the simple use of tumor size and number was insufficient to indicate HCC biological features and to predict the risk of tumor recurrence, some biological markers such as Alphafetoprotein, Des-Gamma-carboxy prothrombin and the neutrophil-to-lymphocyte ratio were useful in selecting LT candidates in HCC patients beyond the MC. For patients with advanced HCC, downstaging therapy is an effective way to reduce the tumor stage to fulfill the MC by using liver-directed therapy such as transarterial chemoembolization, radiofrequency ablation and percutaneous ethanol injection. This article reviews the recent advances in LT for HCC beyond the MC.     

From minimal to maximal surgery in the treatment of hepatocarcinoma:A review

Hepatocellular carcinoma represents one of the most challenging frontiers in liver surgery. Surgeons have to face a broad spectrum of aspects,from the underlying liver disease to the new surgical techniques. Safe liver resection can be performed in patients with portal hypertension and well-compensated liver function witha 5-year survival rate of 50%,offering good longterms results in selected patients. With the advances in laparoscopic surgery,major liver resections can be performed with minimal harm,avoiding the wound and leak complications related to the laparotomies. Studies have shown that oncological margins are the same as in open surgery. In patients submitted to liver resection(either laparoscopic or open) who experience recurrence,re-resection or salvage liver transplantation has been showing to be an alternative approach in well selected cases. The decision making approach to the cirrhotic patient is becoming more complex and should involve hepatologists,liver surgeons,radiologists and oncologists. Better understanding of the different risk factors for recurrence and survival should be aimed in these multidisciplinary discussions. We here in discuss the hot topics related to surgical risk factors regarding the surgical treatment of hepatocellular carcinoma: anatomical resection,margin status,macrovascular tumor invasion,the place of laparoscopy,salvage liver transplantation and liver transplantation.     

Hepatocellular carcinoma: Consensus,controversies and future directions: A report from the Canadian Association for the Study of the Liver Hepatocellular Carcinoma Meeting

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide and its incidence has rapidly increased in North America in recent years. Although there are many published guidelines to assist the clinician, there remain gaps in knowledge and areas of controversy surrounding the diagnosis and management of HCC. In February 2014, the Canadian Association for the Study of the Liver organized a one-day single-topic consensus conference on HCC. Herein, the authors present a summary of the topics covered and the result of voting on consensus statements presented at this meeting.     

Adherence to AASLD guidelines for the treatment of hepatocellular carcinoma in clinical practice: Experience of the Bologna Liver Oncology Group

BackgroundFew data exist on real-life adherence to international guidelines for the treatment of hepatocellular carcinoma. We analysed the rate of adherence to American Association for the Study of Liver Diseases guidelines, to identify reasons for discrepancy with treatments performed in our centre.Methods227 consecutive cirrhotics with a first hepatocellular carcinoma diagnosis (2005–2010) were retrospectively evaluated and stratified based on Barcelona Clinic Liver Cancer system: 126 early, 50 intermediate, 40 advanced, and 11 end stage.ResultsEarly hepatocellular carcinomas were theoretically eligible for resection (n = 27), liver transplantation (n = 36), and percutaneous treatment (n = 63). In practice, 15/27 (55.5%), 31/36 (86.1%), and 22/63 (34.9%) respectively were treated as recommended. Reasons for discrepancy were age/comorbidity, tumour location, ultrasound visibility, surgical contraindications. Transarterial chemoembolisation was performed in 25/126 early hepatocellular carcinomas (19.8%), resection in 11/63 early hepatocellular carcinomas eligible for percutaneous treatment (17.5%). Transarterial chemoembolisation was excluded in 16/50 intermediate hepatocellular carcinomas (32%). Resection or transarterial chemoembolisation was performed in 6/40 advanced hepatocellular carcinomas (15%).ConclusionOverall, 60% of patients were treated according to American Association for the Study of Liver Diseases guidelines. Approximately 28% of hepatocellular carcinomas were “under-treated” and 7% treated more aggressively than recommended. Peculiarities of individual patients can lead the multidisciplinary team to personalise real-life treatments.     

Systematic review of the outcomes of surgical resection for intermediate and advanced Barcelona Clinic Liver Cancer stage hepatocellular carcinoma: A critical appraisal of the evidence

AIM To perform a systematic review to determine the survival outcomes after curative resection of intermediate and advanced hepatocellular carcinomas(HCC).METHODS A systematic review of the published literature was performed using the PubM ed database from 1 st January 1999 to 31 st Dec 2014 to identify studies that reported outcomes of liver resection as the primary curative treatment for Barcelona Clinic Liver Cancer(BCLC) stage B or C HCC. The primary end point was to determine the overall survival(OS) and disease free survival(DFS) of liver resection of HCC in BCLC stage B or C in patients with adequate liver reserve(i.e., Child's A or B status). The secondary end points were to assess the morbidity and mortality of liver resection in large HCC(defined as lesions larger than 10 cm in diameter) and to compare the OS and DFS after surgical resection of solitary vs multifocal HCC.RESULTS We identified 74 articles which met the inclusion criteria and were analyzed in this systematic review. Analysis of the resection outcomes of the included studies were grouped according to(1) BCLC stage B or C HCC,(2) Size of HCC and(3) multifocal tumors. The median 5-year OS of BCLC stage B was 38.7%(range 10.0-57.0); while the median 5-year OS of BCLC stage C was 20.0%(range 0.0-42.0). The collective median 5-year OS of both stages was 27.9%(0.0-57.0). In examining the morbidity and mortality following liver resection in large HCC, the pooled RR for morbidity [RR(95%CI) = 1.00(0.76-1.31)] and mortality [RR(95%CI) = 1.15(0.73-1.80)] were not significant. Within the spectrum of BCLC B and C lesions, tumors greater than 10 cm were reported to have median 5-year OS of 33.0% and multifocal lesions 54.0%.CONCLUSION Indication for surgical resection should be extended to BCLC stage B lesions in selected patients. Further studies are needed to stratify stage C lesions for resection.     

Liver Imaging Reporting and Data System criteria for the diagnosis of hepatocellular carcinoma in clinical practice: A pictorial minireview

Hepatocellular carcinoma (HCC) is the sixth most common cancer. The main risk factors associated with HCC development include hepatitis B virus, hepatitis C virus, alcohol consumption, aflatoxin B1, and nonalcoholic fatty liver disease. However, hepatocarcinogenesis is a complex multistep process. Various factors lead to hepatocyte malignant transformation and HCC development. Diagnosis and surveillance of HCC can be made with the use of liver ultrasound (US) every 6 mo. However, the sensitivity of this imaging method to detect HCC in a cirrhotic liver is limited, due to the abnormal liver parenchyma. Computed tomography (CT) and magnetic resonance imaging (MRI) are considered to be most useful tools for at-risk patients or patients with inadequate US. Liver biopsy is still used for diagnosis and prognosis of HCC in specific nodules that cannot be definitely characterized as HCC by imaging. Recently the American College of Radiology designed the Liver Imaging Reporting and Data System (LI-RADS), which is a comprehensive system for standardized interpretation of CT and MRI liver examinations that was first proposed in 2011. In 2018, it was integrated into the American Association for the Study of Liver Diseases guidance statement for HCC. LI-RADS is designed to ensure high sensitivity, precise categorization, and high positive predictive value for the diagnosis of HCC and is applied to “high-risk populations” according to specific criteria. Most importantly LI-RADS criteria achieved international collaboration and consensus among liver experts around the world on the best practices for caring for patients with or at risk for HCC.