Neoadjuvant therapy in the treatment of hilar cholangiocarcinoma:Review of the literature

Cholangiocarcinoma(CCA) is a malignant tumor of the biliary system and includes, according to the anatomical classification, intra hepatic CCA(iCCA),hilar CCA(hCCA) and distal CCA(dCCA). Hilar CCA is the most challenging type in terms of diagnosis, treatment and prognosis. Surgery is the only treatment possibly providing long-term survival, but only few patients are considered resectable at the time of diagnosis. In fact, tumor's extension to segmentary or subsegmentary biliary ducts, along with large lymph node involvement or intrahepatic metastases, precludes the surgical approach. To achieve R0 margins is mandatory for the disease-free survival and overall survival. In case of unresectable locally advanced hCCA, radiochemotherapy(RCT) as neoadjuvant treatment demonstrated to be a therapeutic option before either hepatic resection or liver transplantation. Before liver surgery, RCT is believed to enhance the R0 margins rate. For patients meeting the Mayo Clinic criteria, RCT prior to orthotopic liver transplant(OLT) has proved to produce acceptable 5-years survivals. In this review, we analyze the current role of neoadjuvant RCT before resection as well as before OLT.     

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??Selection of liver resection and liver transplantation for patients with hepatocellular carcinoma SHEN Feng, WANG Kui, XUE Hui, et al. Eastern Hepatobiliary Surgery Hospital??the Second Military Medical University??Shanghai 200438??China
Corresponding author??SHEN Feng, E-mail:shenfengehbh@
sina.com
Abstract Liver resection (LR) and liver transplantation (LT) are the main radically curative treatments for hepatocellular carcinoma (HCC) currently. For patient with HCC amenable for either treatment, there is still a controversy on selection of LR or LT for tumor at different stages, particularly at intermediate stage. Studies suggested that there was no difference in overall survival between both options for HCC patients within Milan criteria (MC) ,who were optimal candidates for a curative LR. For patients with severe cirrhosis and multiple tumors (≤3) within MC, LT achieved a better long-term survival. Although evidences of comparison of long-term outcomes following both treatments for intermediate HCC beyond MC is still insufficient, several MC -expanded criteria have been proposed, especially, from China, showing optimal accuracy in selecting transplant patients. However, LR+ salvage LT may be another therapeutic strategy worthy of discussion. A well-designed, prospective study which overcomes the selection biasis is urgently required to clarify the prognostic difference between the two treatments.     

肝癌行肝切除术和肝移植的合理选择

肝切除术和肝移植是目前肝细胞癌（以下简称肝癌）的主要根治性治疗手段。在技术上同时适合的前提下,两种治疗在不同分期肝癌,尤其是中期肝癌中如何合理选择,仍存在较大争议。对具有良好肝切除指征的符合米兰标准内肝癌,根治性肝切除术和肝移植的总体生存差异无统计学意义;而对伴严重肝硬化,多发肿瘤（≤3个）的符合米兰标准的病人,肝移植可获得更好远期疗效。两种治疗对超米兰标准的中期肝癌的疗效比较尚缺乏更多证据,但肝移植中米兰标准指征可进一步扩大已有较多共识,尤其是我国学者提出多种肝移植筛选标准,有效提高了肝移植的受益范围。肝切除术加补救性肝移植可能是另一种值得探讨的治疗策略。设计良好、克服肝切除术和肝移植两种治疗之间选择偏移的前瞻性研究值得期待。     

Foreign body granuloma reaction following SIRT mimicking peritoneal metastases: a word of caution

Abstract

Intrahepatic cholangiocarcinoma (iCCA) is the second most common primary liver malignancy with poor survival rates. Surgical resection is the only curative treatment option, yet only a small portion of cases are resectable. In unresectable situations, suggested therapy consists of a systemic chemotherapy regimen with cisplatinum and gemcitabine. Selective internal radiation therapy (SIRT) has been proposed as an alternative treatment option and may lead to downstaging of unresectable iCCA to surgery. We present a case of a female patient diagnosed with an unresectable iCCA treated with SIRT in order to obtain downstaging. Explorative laparoscopy three months later showed multiple peritoneal lesions in the left upper quadrant, mimicking peritoneal metastases. Anatomopathological investigation showed a foreign body granuloma surrounding the SIRT resin particles. These findings have important consequences, as the presence of peritoneal metastases implies a palliative situation. Anatomopathological confirmation of any intra-abdominal lesion mimicking peritoneal metastases should be carried out.     

Liver resection as a bridge to transplantation for hepatocellular carcinoma on cirrhosis: a reasonable strategy?

OBJECTIVE: To assess the viability of a strategy of primary resection with secondary liver transplantation (LT) for hepatocellular carcinoma (HCC) on cirrhosis. SUMMARY BACKGROUND DATA: LT is the optimal treatment of HCC with cirrhosis. Owing to organ shortage, liver resection is considered as a reasonable first-line treatment of patients with small HCC and good liver function, with secondary LT as a perspective in case of recurrence. The viability of such strategy, positively explored in theoretical models, is not documented in clinical practice. METHODS: Among 358 consecutive patients with HCC on cirrhosis treated by liver resection (n = 163; 98 of whom were transplantable) or transplantation (n = 195), the feasibility and outcome of secondary transplantation was evaluated in a 2-step fashion. First, secondary LT for tumor recurrence after resection (n = 17) was compared with primary LT (n = 195), to assess the risk and the outcome of secondary LT in patients who effectively succeeded to be treated by this approach. Second, primary resection in transplantable patients (n = 98) was compared with that of primary LT (n = 195) on an intention-to-treat basis, to assess the outcome of each treatment strategy and to determine the proportion of resected patients likely to be switched for secondary LT. Transplantability of resected patients was retrospectively determined according to selection criteria of LT for HCC. RESULTS: Operative mortality (< or =2 months) of secondary LT was significantly higher than that of primary LT (28.6% versus 2.1%; P = 0.0008) as was intraoperative bleeding (mean transfused blood units, 20.7 versus 10.5; P = 0.0001). Tumor recurrence occurred more frequently after secondary than after primary LT (54% versus 18%; P = 0.001). Posttransplant 5-year overall survival was 41% versus 61% (P = 0.03), and disease-free survival was 29% versus 58% (P = 0.003) for secondary and primary LT, respectively.Of 98 patients treated by resection while initially eligible for transplantation, only 20 (20%) were secondarily transplanted, 17 of whom (17%) for tumor recurrence and 3 (3%) for hepatic decompensation. Transplantability of tumoral recurrence was 25% (17 of 69 recurrences). Compared with primarily transplanted patients, transplantable resected patients had a decreased 5-year overall survival (50% versus 61%; P = 0.05) and disease-free survival (18% versus 58%; P < 0.0001), despite the use of secondary LT.On a multivariate analysis including 271 patients eligible for transplantation and treated by either liver resection or primary LT, liver resection alone (P < 0.0001; risk ratio [RR] = 3.27) or liver resection with secondary LT (P < 0.05; RR= 1.87) emerged as negative independent factors of disease-free survival as compared with primary LT. A number of nodules > 3 (P = 0.002; RR= 2.02) and a maximum tumor size exceeding 30 mm (P < 0.0001; RR=1.93) were also predictive of lower disease-free survival. CONCLUSIONS: LT after liver resection is associated with a higher operative mortality, an increased risk of recurrence, and a poorer outcome than primary LT. In addition, liver resection as a bridge to LT impairs the patient transplantability and the chance of long-term survival of cirrhotic patients with HCC. Primary LT should therefore remain the ideal choice of treatment of a cirrhotic patient with HCC, even when the tumor is resectable.     

Liver transplantation with neoadjuvant chemoradiation is more effective than resection for hilar cholangiocarcinoma

OBJECTIVE: Compare survival after neoadjuvant therapy and liver transplantation with survival after resection for patients with hilar CCA. SUMMARY BACKGROUND DATA: We developed a protocol combining neoadjuvant radiotherapy, chemosensitization, and orthotopic liver transplantation for patients with operatively confirmed stage I and II hilar CCA in 1993. Since then, patients with unresectable CCA or CCA arising in the setting of PSC have been enrolled in the transplant protocol. Patients with tumors amenable to resection have undergone excision of the extrahepatic duct with lymphadenectomy and liver resection. METHODS: We reviewed our experience between January 1993 and August 2004 and compared patient survival between the treatment groups. RESULTS: Seventy-one patients entered the transplant treatment protocol and 38 underwent liver transplantation. Fifty-four patients were explored for resection. Twenty-six (48%) underwent resection, and 28 (52%) had unresectable disease. One-, 3-, and 5-year patient survival were 92%, 82%, and 82% after transplantation and 82%, 48%, and 21% after resection (P = 0.022). There were fewer recurrences in the transplant patients (13% versus 27%). CONCLUSIONS: Liver transplantation with neoadjuvant chemoradiation achieved better survival with less recurrence than conventional resection and should be considered as an alternative to resection for patients with localized, node-negative hilar CCA.     

不同部位胆管癌患者术后生存的影响因素分析

背景与目的 目前,胆管癌（CCA）的首选治疗仍为外科手术,但术后复发率较高,患者生存率低。对CCA患者术后生存影响因素的分析将有助于优化手术策略,从而一定程度上改善患者预后。因此,本研究探讨不同部位CCA患者术后生存的影响因素,为临床提供参考。方法 回顾性分析2011年1月—2020年3月133例行手术治疗的CCA患者临床病理资料,其中,肝内胆管癌（iCCA）58例,肝门胆管癌（hCCA）30例,远端胆管癌（dCCA）45例,分析临床病理特征与患者生存的关系与预后影响因素。结果 iCCA患者术后1、2、3、5年的生存率分别为41.38%、22.41%、8.62%、3.45%,单因素分析显示,iCCA患者的术后生存与合并胆道结石、术前血清白蛋白（ALB）水平、凝血酶时间、CEA、CA125、CA19-9、Child-Pugh分级、肿块最大直径、是否R₀切除、淋巴结转移情况、肿瘤分化程度有关（均P<0.05）;多因素分析显示,术前ALB水平、凝血酶时间、CA19-9、Child-Pugh分级、肿块最大直径及是否R₀切除是iCCA患者术后生存的独立影响因素（均P<0.05）。hCCA患者术后1、2、3、5年的生存率分别为43.33%、20.0%、6.67%、3.33%,单因素分析显示,hCCA患者的术后生存与术前CEA水平、是否R₀切除、淋巴结转移情况、肿瘤分化程度、肿块最大直径、是否侵犯门静脉有关（均P<0.05）;多因素分析显示,是否行R₀切除、淋巴结转移情况、肿瘤分化程度、是否侵犯门静脉及肿块最大直径是hCCA患者术后生存的独立影响因素（均P<0.05）。dCCA患者术后1、2、3、5年的生存率分别为62.22%、31.11%、17.78%、14.29%,单因素分析显示,dCCA患者的术后生存与淋巴结转移情况、肿瘤分化程度有关（均P<0.05）。多因素分析显示,淋巴结转移情况、肿瘤分化程度及是否R₀切除是dCCA患者术后生存的独立影响因素（均P<0.05）。dCCA患者术后生存时间优于iCCA和hCCA患者,但差异无统计学意义（均P>0.05）。结论 不同部位CCA有大致共同的预后影响因素,通过评估这些因素有助于预测CCA预后,完善对CCA患者的分层标准,优化术前和术后治疗方案,延长患者生存时间。     

Treatment of hepatocellular carcinoma with macroscopic vascular invasion: A systematic review and network meta-analysis

BackgroundThis study aimed to evaluate the outcomes of different treatments for patients with hepatocellular carcinoma (HCC) and macroscopic vascular invasion.MethodsA systematic review and meta-analysis of comparative studies was performed to evaluate various treatment modalities for HCC with macroscopic vascular invasion, including liver resection (LR), liver transplantation (LT), transarterial chemoembolization (TACE), transarterial radioembolization (TARE), radiotherapy (RT), radiofrequency ablation (RFA), and antineoplastic systemic therapy (AnST).ResultsAfter applying the selection criteria, 31 studies were included. The surgical resection (SR) group (including LR and LT) had a similar mortality rate to the non-surgical resection (NS) group (RD = −0.01; 95% CI -0.05 to 0.03). The SR group had a higher rate of complications (RD = 0.06; 95% CI 0.00 to 0.12) but a higher 3-year overall survival (OS) rate than the NS group (RD = 0.12; 95% CI 0.05 to 0.20). The network analysis revealed that the overall survival was lower in the AnST group. LT and LR had similar survival benefits. The meta-regression suggested that SR has a greater impact on the survival of patients with impaired liver function.DiscussionMost likely, LT has a significant impact on long-term survival and consequently would be a better option for HCC with macroscopic vascular invasion in patients with impaired liver function. LT and LR offer a higher chance of long-term survival than NS alternatives, although LR and LR are associated with a higher risk of procedure-related complications.     

肝移植治疗成人慢加急性肝功能衰竭的现状

慢加急性肝功能衰竭(ACLF)是慢性肝病或肝硬化急性失代偿期的最严重形式, 往往同时合并肝外器官功能衰竭, 患者短期预后极差。ACLF的触发病因复杂多样, 其分期及器官功能衰竭的类型和定义各不相同, 目前尚无统一的ACLF诊断标准, 难以直接预测和比较不同地域ACLF的总体发病率和预后情况。越来越多的研究证据表明, 肝移植在ACLF外科治疗中发挥重要作用, 但其价值尚存争议。目前ACLF具体的入院处理和治疗方案, 包括ICU的监护治疗、器官功能的支持维护、肝移植手术指征和时机选择等方面, 尚未形成统一的标准化流程或意见。ACLF患者是否应较其他潜在的肝移植等待受者在供者分配方面更具有优先权亦无定论。此外, 人工肝支持系统在ACLF移植前桥接治疗中的应用价值尚需更多的前瞻性对照研究来进一步证实。因此, 本文就肝移植在成人ACLF外科治疗中的指征选择、手术疗效及影响因素、手术时机选择、供肝资源分配及移植前桥接治疗等方面进行探讨, 以期为ACLF肝移植治疗的未来临床研究提供新的方向。     

Prognostic Impact of Sarcomatous Change of Hepatocellular Carcinoma in Patients Undergoing Liver Resection and Liver Transplantation

Sarcomatous change has been rarely observed in hepatocellular carcinoma (HCC), but it is usually associated with very aggressive tumor behavior and widespread metastasis. To assess the impact of sarcomatous changes, we analyzed the outcomes of 15 patients with sarcomatous HCC after resection (n = 11) or liver transplantation (LT) (n = 4). No imaging findings characteristic of sarcomatous changes were observed. According to modified pathological tumor-node metastasis staging, the HCC lesions were classified as stage II in five patients, stage III in six, stage IVa2 in two, and stage IVb in one. The Milan criteria were met in 7 of 15 patients, including 3 of 4 in the LT group. R0 resection was achieved in 9 of 11 resected patients, and their 3-year overall and disease-free survival rates were both 18.2%. In the LT group, 3-year overall and disease-free survival rates were 37.5 and 25%, respectively. In patients within the Milan criteria, 2-year overall survival rate was 25% after resection and 33% after LT, showing no prognostic difference. Extrahepatic metastasis as initial recurrence was detected in 80% after resection and 66.7% after LT. In conclusion, we found that the prognosis of patients with sarcomatous HCC was very unfavorable after either resection or LT and that, except for liver biopsy, no diagnostic method could distinguish between sarcomatous and ordinary HCC. Vigorous postoperative systemic surveillance may be helpful for timely detection and treatment of localized metastases.     

Liver transplantation for hilar cholangiocarcinoma: A systematic review

Patients with hilar cholangiocarcinoma (hCCA) have advanced disease at presentation and therefore curative treatment options are limited. Liver transplantation (LT), in the case of unresectable disease, is theoretically an attractive option, as it offers the maximum resection margin and at the same time removes the underlying parenchymal liver disease. In the past years a number of studies have aimed to evaluate to potential beneficial role of neo adjuvant therapy followed by LT for treating patients with unresectable hCCA. The objective of our systematic review was to collect and evaluate long-term outcomes of patients with hCCA undergoing LT. A systematic search of 4 electronic databases (Medline, Scopus, Google Scholar and ClinicalTrails.gov databases) was performed for articles published between January 2000 and May 2019. A total of 13 studies with 698 patients were finally included in the present systematic review. A proportion of 74.4% of patients received combination of chemotherapy and radiation as a part of neoadjuvant therapy. One-, 3- and 5-year overall survival rates ranged greatly among the included studies from 58% to 92%, 31% to 80% and 20% to 74%, respectively. Recurrence rates ranged from 16% to 61%, whilst perioperative mortality ranged from 0% to 25.5%. LT could provide acceptable long-term outcomes in the setting of neoadjuvant chemoradiation and strict patient selection criteria. Taking into account organ shortage, combined with the lack of level I evidence, more prospective randomized trials are needed in order to establish certain indications, rigorous criteria and standardized protocols for LT in hCCA and provide the maximal potential benefits for these patients.     

Photodynamic Therapy Provides Local Control of Cholangiocarcinoma in Patients Awaiting Liver Transplantation

Many transplant centers use endoscopically directed brachytherapy to provide locoregional control in patients with otherwise incurable cholangiocarcinoma (CCA) who are awaiting liver transplantation (LT). The use of endoscopic retrograde cholangiopancreatography (ERCP)‐directed photodynamic therapy (PDT) as an alternative to brachytherapy for providing locoregional control in this patient population has not been studied. The aim of this study was to report on our initial experience using ERCP‐directed PDT to provide local control in patients with unresectable CCA who were awaiting LT. Patients with unresectable CCA who underwent protocol‐driven neoadjuvant chemoradiation and ERCP‐directed PDT with the intent of undergoing LT were reviewed. Four patients with confirmed or suspected CCA met the inclusion criteria for protocol LT. All four patients (100%) successfully underwent ERCP‐directed PDT. All patients had chemoradiation dose delays, and two patients had recurrent cholangitis despite PDT. None of these patients had progressive locoregional disease or distant metastasis following PDT. All four patients (100%) underwent LT. Intention‐to‐treat disease‐free survival was 75% at mean follow‐up of 28.1 months. In summary, ERCP‐directed PDT is a reasonably well tolerated and safe procedure that may have benefit by maintaining locoregional tumor control in patients with CCA who are awaiting LT.     

El trasplante hepático aumenta la resecabilidad R0 y la supervivencia de los pacientes con tumor de Klatskin irresecable no diseminado

IntroductionThere are no established indications for Liver transplant (LT) in patients with a Klatskin tumour (KT) due to the differences in the published results.ObjectiveTo report on our patients who have non-disseminated unresectable KT and who were given a LT, and to compare results with those of patients who have had tumour resection and those who have not.Patients and methodWe have treated 75 patients diagnosed with KT. The mean age was 62±11 years (range: 38–88 years) and 50 were males (66%). Twenty patients were inoperable. Of the 55 patients who underwent surgery: tumour resection (TR) was performed in 29 cases; there was no tumour dissemination in 11 unresectable cases and therefore these patients were added to the LT waiting list and the remaining 15 unresectable cases had tumour dissemination and remained on palliative treatment.ResultsIn the LT group there was no postoperative mortality (during the first month) and the survival rate was 95%, 59% and 36% with a disease-free survival of 75%, 40% and 20%; whereas the patients given RT had a survival rate of 80%, 52% and 38% at 1, 3 and 5 years, with a disease-free survival of 65%, 35% and 19%, without any differences compared to the LT group. Patients with unresectable tumour left on palliative therapy had a lower survival than the unresectable who underwent LT (p<0.001).ConclusionsIn patients with non-disseminated unresectable KT, LT has a similar survival to that obtained in cases with resectable R0 liver resection. LT improves the survival rate achieved using palliative treatment in patients with non-disseminated unresectable KT.     

Rescue liver transplantation after post-hepatectomy acute liver failure: A systematic review and pooled analysis

BackgroundPost-hepatectomy liver failure is a severe complication after major liver resection and is associated with a high mortality rate. Nevertheless, there is no effective treatment for severe liver failure. In such a setting, rescue liver transplantation (LT) is used only in extraordinary cases with unclear results. This systematic review aims to define indication of LT in post-hepatectomy liver failure and post-LT outcomes, in terms of patient and disease-free survivals, to assess the procedure's feasibility and effectiveness.MethodsA systematic review of all English language full-text articles published until September 2022 was conducted. Inclusion criteria were articles describing patients undergoing LT for post-hepatectomy liver failure after liver resection, which specified at least one outcome of interest regarding patient/graft survival, postoperative complications, tumour recurrence and cause of death. A pseudo-individual participant data meta-analysis was performed to analyse data. Study quality was assessed with MINORS system. PROSPERO CRD42022349358.ResultsPostoperative complication rate was 53.6%. All patients transplanted for benign indications survived. For malignant tumours, 1-, 3- and 5-year overall survival was 94.7%, 82.1% and 74.6%, respectively. The causes of death were tumour recurrence in 83.3% of cases and infection-related in 16.7% of LT recipients. At Cox regression, being transplanted for unconventional malignant indications (colorectal liver metastasis, cholangiocarcinoma) was a risk factor for death HR = 8.93 (95%CI = 1.04–76.63; P-value = 0.046). Disease-free survival differs according to different malignant tumours (P-value = 0.045).ConclusionsPost-hepatectomy liver failure is an emergent indication for rescue LT, but it is not universally accepted. In selected patients, LT can be a life-saving procedure with low short-term risks. However, special attention must be given to long-term oncological prognosis before proceeding with rescue LT in an urgent setting, considering the severity of liver malignancy, organ scarcity, the country's organ allocation policies and the resource of living-related donation.     

Current treatment of hepatocellular carcinoma. Analysis of a series of 123 cases over a 5-year period

We analyze a 123-cases experience over a 5-year period in the treatment of hepatocellular carcinoma (HCC). Liver resection, transplantation and hyperthermic ablation of the tumor were used according to the indication and patient selection. Systemic chemotherapy followed resection in 18 cases and hyperthermic ablation in 5 cases. Chemo-embolisation was performed in patients to be transplanted and in other two patients with tumor destruction. A number of 86 liver resections were performed in 84 patients (2 re- resections in 1 patient, subsequently transplanted) - 43 on normal liver and 41 on cirrhotic liver. Postoperative mortality was 4.7% in non-cirrhotic and 4.9% in cirrhotic patients. Survival in non-cirrhotic patients was 77% at 1 year, 65% at 2 years, and constant - 45% at 3 and 4 years, whereas in cirrhotic patients it was 60%, 56%, 56% and 36% (Kaplan-Meyer actuarial survival rates). Nine patients underwent liver transplantation (4 OLTs, 3 living donor LT, 1 split LT and 1 "domino" LT); postoperative mortality was 11% (1 patient). At present five patients are alive and well. One patient died by peritoneal carcinomatosis at 10 months; another patient died at 6 months by severe cholestatic recurrent C virus hepatitis and one patient was discharged with permanent severe neurologic disturbances. In 31 patients hyperthermic ablation of the tumor was used with zero mortality. Actuarial survival rates were 75% at one year and 67% at 2 years. In conclusion, in non-cirrhotic patients with HCC resection is the treatment of choice. In cirrhotic patients limited resections should be preferred and liver transplantation is the best solution in selected cases; local ablative methods may be used for some unresectable tumors. The role of adjuvant chemotherapy has to be determined in future comparative studies.     

HCC: current surgical treatment concepts

PURPOSE: The purpose of this study is to review indications and results of surgical treatments of hepatocellular carcinoma (HCC). This tumor, which represents one of the most common malignancies worldwide, is characterized by its prominent development in patients with chronic liver disease (CLD). Liver transplantation (LT) is considered as the ideal treatment of limited HCC removing both tumor(s) and the pre-neoplasic underlying diseased liver. However, this treatment, which is not available in many countries, is restricted to patients with minimum risk of tumor recurrence under immunosuppression. The risk of recurrence is minimized in patients fulfilling the Milan criteria with a tendency to accept slight expansion of size in patients with favourable natural history and low AFP level. Increasing duration in the waiting list before LT leads several teams to use neoadjuvant therapies such as percutaneous ablation, TACE and liver resection. Liver resection in cirrhotic patients with good liver function remains the most available efficient treatment of patients with HCC. Better liver function assessment, understanding of the segmental liver anatomy with more accurate imaging studies and surgical technique refinements are the most important factors that have contributed to reduce mortality with an expecting 5 years survival of 70%. There is considerable interest in combined treatment associating resection and LT. Transplantable patients with good liver function should be considered for liver resection as primary therapy and for LT in case of tumor recurrence. This salvage strategy is refined using pathological analysis of the resected specimen which identifies histological pejorative factors allowing selecting patients who should transplanted before recurrence. CONCLUSIONS: The improvement of survival in HCC patients after surgical treatment results from refinements in surgical technique and better identification of adverse prognostic factors.     

Number and Tumor Size Are Not Sufficient Criteria to Select Patients for Liver Transplantation for Hepatocellular Carcinoma

Background

Hepatocellular carcinoma (HCC) is an indication for liver resection or transplantation (LT). In most centers, patients whose HCC meets the Milan criteria are considered for LT. The first objective of this study was to analyze whether there is a correlation between the pathologic characteristics of the tumor, survival and recurrence rate. Second, we focused our attention on vascular invasion (VI).

Methods

From January 1997 to December 2007, a total of 196 patients who had a preoperative diagnosis of HCC were included. The selection criteria for LT satisfied both the Milan and the San Francisco criteria (UCSF). Demographic, clinical, and pathologic information were recorded.

Results

HCC was confirmed in 168 patients (85.7%). The median follow-up was 74?months. The pathologic findings showed that 106 patients (54.1%) satisfied the Milan criteria, 134 (68.4%) the UCSF criteria of whom 28 (14.3%) were beyond the Milan criteria but within the UCSF criteria, and 34 (17.3%) beyond the UCSF criteria. VI was detected in 41 patients (24%). The 1-, 3-, and 5-year overall survival rates were 90%, 85%, and 77%, respectively, according to the Milan criteria and 90%, 83%, and 76%, respectively, according to the UCSF criteria (P?=?NS). In univariate and multivariate analyses, tumor size and VI were significant prognostic factors affecting survival (P?400?ng/ml and tumor grade G3.

Conclusions

Tumor size and VI were the only significant prognostic factors affecting survival of HCC patients. Primary liver resection could be a potential selection treatment before LT.     

Hepatocellular carcinoma in Child's A cirrhosis: a retrospective analysis of matched pairs following liver transplantation vs. liver resection according to the intention‐to‐treat principle

This is the first matched pair analysis on the puzzling clinical problem of whether to perform liver transplantation (LT) or liver resection (LR) for Child's A hepatocellular carcinoma (HCC) patients. A total of 201 patients diagnosed with HCC and Child's A liver cirrhosis were treated with LT transarterial chemoembolization (TACE) or LR between 1998 and 2012. To achieve the most accurate study design, two groups of 57 patients were matched retrospectively according to their tumor characteristics detected by the initial computerized tomography (CT) scan. Sixteen of 57 LT candidates were not transplanted due to tumor progress during pre‐treatment (TACE). Nevertheless, the retrospective analysis of the matched pairs according to the intention‐to‐treat principle resulted in a better five‐yr overall survival (OS) rate of 54.3% for the group of LT candidates compared with 35.7% for those receiving LR (p = 0.19). In patients meeting the University of California, San Francisco (UCSF) criteria, five‐yr OS reached 58.4% after LT and 45.1% after LR (p = 0.56). For Milan criteria (MC) patients, LT resulted in 57.9% and LR in 42% five‐yr OS rate (p = 0.29). In conclusion, the finding of a better OS rate in LT was not statistically significant. There was also a selection bias in favor of LT, which may have influenced the OS. Therefore, particularly in regard to organ scarcity, LR remains a viable treatment option for respectable HCC in Child's A cirrhosis.     

Liver transplantation for unresectable hepatocellular carcinoma in patients without liver cirrhosis

Summary Hepatocellular carcinoma (HCC) arising in noncirrhotic and nonfibrotic liver (NC‐HCC) is a rare type of malignancy frequently found in healthy young individuals. Partial liver resection is the treatment of choice with expected 5‐year survival rates between 40% and 70%. As a result of absence of any symptom, a considerable number of patients are diagnosed when the malignancy has progressed to an advanced stage and the tumor has turned already unresectable. Some other patients suffer from intrahepatic recurrence after previous liver resection that cannot be re‐resected or locally ablated. In these situations, liver transplantation (LT) may be the only potentially curative treatment. The indication for LT in NC‐HCC patients, however, is not well established. The preliminary results of recent analysis of the European Liver Transplant Registry (ELTR) together with a literature review identified over 150 patients transplanted for NC‐HCC during the last 15 years. In contrast to the historical data, these studies showed 5‐year survival rates at 50–70% in well‐selected patients. Important determinants of poor outcome are macrovascular invasion, lymph node involvement, and time interval of <12 months when LT is used as rescue therapy for intrahepatic recurrence after a previous partial liver resection. Interestingly, outcomes after both liver resection and LT for NC‐HCC are much less influenced by tumor size than is the case with cirrhotic HCC. A large tumor size per se should, therefore, not to be seen as a strict contraindication for performing LT in patients with NC‐HCC.