Neoadjuvant treatment strategies for intrahepatic cholangiocarcinoma

Intrahepatic cholangiocarcinoma(ICC) is the second most common primary liver malignancy and is increasing in incidence. Long-term outcomes are optimized when patients undergo margin-negative resection followed by adjuvant chemotherapy. Unfortunately, a significant proportion of patients present with locally advanced, unresectable disease. Furthermore, recurrence rates are high even among patients who undergo surgical resection. The delivery of systemic and/or liver-directed therapies prior to surgery may increase the proportion of patients who are eligible for surgery and reduce recurrence rates by prioritizing early systemic therapy for this aggressive cancer. Nevertheless, the available evidence for neoadjuvant therapy in ICC is currently limited yet recent advances in liver directed therapies, chemotherapy regimens, and targeted therapies have generated increasing interest its role. In this article, we review the rationale for, current evidence for, and ongoing research efforts in the use of neoadjuvant therapy for ICC.     

Chinese expert consensus on neoadjuvant and conversion therapies for hepatocellular carcinoma

The low resection and high recurrence rates in hepatocellular carcinoma (HCC) are the major challenges to improving prognosis. Neoadjuvant and conversion therapies are underlying strategies to overcome these challenges. To date, no guideline or consensus has been published on the neoadjuvant and conversion therapies in HCC. Recent studies showed that neoadjuvant therapy for resectable HCC and conversion therapy for unresectable HCC are safe, feasible, and effective. Neoadjuvant and conversion therapies have the following advantages in treating HCC: R0 resection with sufficient volume of future liver remnant, relatively simple operation, and wide applicability. Therefore, it was necessary to conduct a widely accepted consensus among the experts in China who have extensive expertise and experience in treating HCC using neoadjuvant and conversion therapies, which is important to standardize the application of neoadjuvant and conversion therapies for the management of HCC. The strategies of neoadjuvant therapy include the selection of the eligible patients, therapy regimen, cycles, effect evaluations, and multidisciplinary treatment. The management of patients with insufficient volume of future liver remnant and patients who cannot achieve R0 resection is the key to the strategies of conversion therapy. Here, we present the resultant evidence- and experience-based consensus to guide the application of neoadjuvant and conversion therapies in clinical practice.     

Salvage locoregional therapies for recurrent hepatocellular carcinoma

Hepatocellular carcinoma(HCC) is the second most common cause of cancerrelated death worldwide. Despite the advent of screening efforts and algorithms to stratify patients into appropriate treatment strategies, recurrence rates remain high. In contrast to first-line treatment for HCC, which relies on several factors, including clinical staging, tumor burden, and liver function, there is no consensus or general treatment recommendations for recurrent HCC(R-HCC). Locoregional therapies include a s...     

The current role of neoadjuvant/adjuvant/chemoprevention therapy in partial hepatectomy for hepatocellular carcinoma:a systematic review

BACKGROUND:Following curative treatment for hepato-cellular carcinoma(HCC),50%-90% of postoperative death is due to recurrent disease.Intra-hepatic recurrence is frequently the only site of recurrence.Thus,any neoadjuvant or adjuvant therapy,which can decrease or delay the incidence of intra-hepatic recurrence,or any cancer chemoprevention which can prevent a new HCC from developing in the liver remnant,will improve the results of liver resection.This article systematically reviewed the current evidence of ...     

Neoadjuvant and Adjuvant Therapy in Intrahepatic Cholangiocarcinoma

Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer and causes major economic and health burdens throughout the world. Although the incidence of ICC is relatively low, an upward trend has been seen over the past few decades. Owing to the lack of specific manifestations and tools for early diagnosis, most ICC patients have relatively advanced disease at diagnosis. Thus, neoadjuvant therapy is necessary to evaluate tumor biology and downstage these patients so that appropriate candidates can be selected for radical liver resection. However, even after radical resection, the recurrence rate is relatively high and is a main cause leading to death after surgery, which makes adjuvant therapy necessary. Because of its low incidence, studies in both neoadjuvant and adjuvant settings of ICC are lagging compared with other types of malignancy. While standard neoadjuvant and adjuvant regimens are not available in the current guidelines due to a lack of high-level evidence, some progress has been achieved in recent years. In this review, the available literature on advances in neoadjuvant and adjuvant strategies in ICC are evaluated, and possible challenges and opportunities for clinical and translational investigations in the near future are discussed.     

Resection of hepatitis B virus-related hepatocellular carcinoma: Evolving strategies and emerging therapies to improve outcome

The incidence of hepatocellular carcinoma (HCC) is increasing worldwide, largely due to hepatitis B virus (HBV), hepatitis C virus and liver cirrhosis. Chronic HBV infection is estimated to cause 55%-60% of the cases of HCC worldwide and over 70% in Asian countries. Liver resection is currently the mainstay of treatment due to the low surgical mortality, a wider treatment indication, and simplicity of post-treatment follow-up. There is an ever-increasing demand on surgeons to perform curative liver resection in HCC, with the hope of avoiding tumor recurrences. Hepatitis B-related-HCC has distinct clinicopathological features, which should be considered when treating the disease. The author presents a review of the recently evolving strategies and emerging therapies to improve HCC postresectional outcomes and focus on perioperative measures to improve patient outcome, with particular reference to the current status of adjuvant therapies in HCC patients after liver resection.     

局部消融在肝细胞癌治疗中的应用

手术切除和肝移植被认为是肝细胞癌(HCC)根治性治疗手段,但仅有10%~20%的HCC患者能接受这些治疗。近些年来,射频消融、微波消融、冷冻消融及新近出现的不可逆电穿孔消融等局部治疗方法逐渐成为无法手术患者的替代治疗。除了局部控制肿瘤生长改善预后外,消融技术还有助于肿瘤降级以便二次切除。重点介绍了射频消融及联合其他治疗手段治疗HCC的进展,对射频消融与其他局部消融进行了比较,简述了智能导航技术在辅助消融中的应用,认为随着影像医学的发展以及其他相关领域的进步,未来消融技术在临床应用中将更加广泛。     

Hepatocellular carcinoma: locoregional and targeted therapies

HCC is a leading cause of morbidity and mortality worldwide. Advances in cancer screening and surveillance have allowed for earlier detection of tumors, affording greater treatment potential. The advent of locoregional therapies has generated greater treatment options for patients with HCC. Either alone or in combination as an adjuvant or neoadjuvant therapy, these novel approaches continue to hold promise for improving morbidity and/or mortality of patients with HCC. The emergence of systemic molecular targeted therapies increases the role of translational science. Whereas surgical resection and transplantation conventionally form the cornerstone of curative approaches, the advancement of locoregional therapies holds great promise in adding to the curative armamentarium.     

Current management of patients with hepatocellular carcinoma

The current management therapies for hepatocellular carcinoma(HCC) patients are discussed in this review. Despite the development of new therapies, HCC remains a "difficult to treat" cancer because HCC typically occurs in advanced liver disease or hepatic cirrhosis. The progression of multistep and multicentric HCC hampers the prevention of the recurrence of HCC. Many HCC patients are treated with surgical resection and radiofrequency ablation(RFA), although these modalities should be considered in only selected cases with a certain HCC number and size. Although there is a shortage of grafts, liver transplantation has the highest survival rates for HCC. Several modalities are salvage treatments; however, intensive care in combination with other modalities or in combination with surgical resection or RFA might offer a better prognosis. Sorafenib is useful for patients with advanced HCC. In the near future, HCC treatment will include stronger molecular targeted drugs, which will have greater potency and fewer adverse events. Further studies will be ongoing.     

Leberresektion vs. Lebertransplantation bei HCC

Hepatocellular carcinoma (HCC) is the fifth most common cancer in men and the ninth most common cancer in women in the world. For surgical treatment, two options are available: surgical resection and orthotopic liver transplantation. The treatment algorithms in Germany are currently determined by the S3 guideline and by the revised guideline for organ transplantation; however, the final decision should be discussed on an individual basis in an interdisciplinary tumor conference. Surgical resection is recommended for all patients with resectable HCC without underlying cirrhosis or compensated chronic liver disease and sufficient liver function. Resection should be minimally invasive and parenchyma-sparing. For HCC in cirrhosis within the Milan criteria, liver transplantation is indicated in principle. A match model for end-stage liver disease (matchMELD) can be applied in order to facilitate timely organ allocation. Due to the organ shortage, liver donations from living donors should be evaluated. Bridging therapies such as transarterial chemoembolization are recommended. For non-transplantable patients, surgical resection or radiofrequency ablation is recommended in regard to the functional resectability.     

Hepatocellular carcinoma: Advances in diagnosis,management, and long term outcome

Hepatocellular carcinoma (HCC) remains a common and lethal malignancy worldwide and arises in the setting of a host of diseases. The incidence continues to increase despite multiple vaccines and therapies for viruses such as the hepatitis B and C viruses. In addition, due to the growing incidence of obesity in Western society, there is anticipation that there will be a growing population with HCC due to non-alcoholic fatty liver disease. Due to the growing frequency of this disease, screening is recommended using ultrasound with further imaging using magnetic resonance imaging and multi-detector computed tomography used for further characterization of masses. Great advances have been made to help with the early diagnosis of small lesions leading to potential curative resection or transplantation. Resection and transplantation maybe used in a variety of patients that are carefully selected based on underlying liver disease. Using certain guidelines and clinical acumen patients may have good outcomes with either resection or transplantation however many patients are inoperable at time of presentation. Fortunately, the use of new locoregional therapies has made down staging patients a potential option making them potential surgical candidates. Despite a growing population with HCC, new advances in viral therapies, chemotherapeutics, and an expanding population of surgical and transplant candidates might all contribute to improved long-term survival of these patients.     

Emerging curative-intent minimally-invasive therapies for hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the most common cause of liver malignancy and the fourth leading cause of cancer deaths universally. Cure can be achieved for early stage HCC, which is defined as 3 or fewer lesions less than or equal to 3 cm in the setting of Child-Pugh A or B and an ECOG of 0. Patients outside of these criteria who can be down-staged with loco-regional therapies to resection or liver transplantation (LT) also achieve curative outcomes. Traditionally, surgical resection, LT, and ablation are considered curative therapies for early HCC. However, results from recently conducted LEGACY study and DOSISPHERE trial demonstrate that transarterial radio-embolization has curative outcomes for early HCC, leading to its recent incorporation into the Barcelona clinic liver criteria guidelines for early HCC. This review is based on current evidence for curative-intent loco-regional therapies including radioembolization for early-stage HCC.     

Future perspectives for hepatocellular carcinoma

BACKGROUND: Five facets of hepatocellular carcinoma (HCC) are identified that impact on future directions in the management of the disease: epidemiology, prevention, screening, diagnosis and therapy. Recent papers on HCC have been reviewed, and predictions have been made on developments in HCC over the next decade. DISCUSSION: It is predicted that hepatitis B-related HCC will decrease with vaccination, while hepatitis C-related HCC will become an increasing problem. Antiviral treatment and chemopreventive agents will prevent HCC development. Whole-population screening will not be an option, but screening is justified for individuals who can pay for it. There will be more emphasis on the use of tumour markers. Transabdominal ultrasound and triphasic spiral computed tomography will remain important radiological imaging techniques. The results of liver resection will not improve unless neoadjuvant/adjuvant therapy is proven to be effective. More patients with initially unresectable HCC will be down-staged to become resectable with improvements in local, regional and systemic therapies. Liver transplantation will be increasingly used. Local ablative therapy will improve the quality of survival but will have no impact on overall survival compared with surgical resection. The author hopes to review the accuracy of these predictions in 2013.     

Stem Cell Origins and Animal Models of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is a common malignant tumor that almost always occurs within a preexisting background of chronic liver disease and cirrhosis. Currently, medical therapy is not effective in treating most HCC, and the only hope of cure is either resection or liver transplantation. A small minority of patients is eligible for these therapies, which entail major morbidity at the very least. In spite of immense scientific advances during the past 3 decades, patient survival has improved very little. In order to reduce morbidity and mortality from HCC, improvements in early diagnosis and development of novel local and systemic therapies for advanced disease are essential, in addition to efforts geared towards primary prevention. Studies with experimental animal models that closely mimic human disease are very valuable in understanding physiological, cellular and molecular mechanisms underlying the disease. Furthermore, appropriate animal models have the potential to increase our understanding of the effects of image-guided minimally invasive therapies and thereby help to improve such therapies. In this review, we examine the evidence for stem cell origins of such tumors, critically evaluate existing models and reflect on how to develop new models for minimally invasive, image-guided treatment of HCC.     

Hepatocellular carcinoma:Surgical perspectives beyond the barcelona clinic liver cancer recommendations

The barcelona clinic liver cancer(BCLC)staging system has been approved as guidance for hepatocellular carcinoma(HCC)treatment guidelines by the main Western clinical liver associations.According to the BCLC classification,only patients with a small single HCC nodule without signs of portal hypertension or hyperbilirubinemia should undergo liver resection.In contrast,patients with intermediate-advanced HCC should be scheduled for palliative therapies,even if the lesion is resectable.Recent studies report good short-term and long-term outcomes in patients with intermediate-advanced HCC treated by liver resection.Therefore,this classification has been criticised because it excludes many patients who could benefit from curative resection.The aim of this review was to evaluate the role of surgery beyond the BCLC recommendations.Safe liver resection can be performed in patients with portal hypertension and well-compensated liver function with a 5-year survival rate of 50%.Surgery also offers good long-term result in selected patients with multiple or large HCCs with a reported 5-year survival rate of over 50%and 40%,respectively.Although macrovascular invasion is associated with a poor prognosis,liver resection provides better long-term results than palliative therapies or best supportive care.Recently,researchers have identified several genes whose altered expression influences the prognosis of patients with HCC.These genes may be useful for classifying the biological behaviour of different tumours.A revision of the BCLC classification should be introduced to provide the best treatment strategy and to ensure the best prognosis in patients with HCC.     

Neoadjuvant treatment for pancreatic cancer--a review

Pancreatic cancer is associated with a poor prognosis. While surgical resection is the only treatment that holds the potential of cure, a minority of patients are surgical candidates. Despite surgery, the overall survival rates remain low. Neoadjuvant treatment has been investigated both in the setting of resectable disease at diagnosis, or in an attempt to downstage locally advanced disease for resection. Single institution studies of neoadjuvant chemoradiation have demonstrated favourable outcomes, compared to similar series of patients treated with surgery with or without adjuvant therapy. For unresectable disease, partial or complete responses have been observed which have allowed some patients to subsequently undergo resection. The reports of neoadjuvant therapy for pancreatic cancer are heterogeneous with regards to patient population, treatment methods and modalities, making comparisons of different regimens inherently flawed. To date, no randomized controlled trials of neoadjuvant therapy have been conducted, however given the positive outcomes of single institutional series of neoadjuvant therapy this approach is worthy of further study.     

Treatment of hepatocellular carcinoma: Steps forward but still a long way to go

Hepatocellular carcinoma(HCC) is the fifth most common malignancy and the third cause of tumor associated deaths worldwide. HCC incidence rates are increasing in many parts of the world including developing and developed countries. Potentially curative treatments for HCC are resection and liver transplantation, but these are only suitable for patients with small tumors, meeting strict pre-defined criteria, or well-compensated liver disease. Early diagnosis of HCCcan be achieved by surveillance of at-risk populations. For patients with non-resectable disease treatments modalities include loco-ablative and systemic therapies. In this review we focus on treatment options in HCC and their allocation. Although significant research is in progress, to this date, the results are unsatisfactory with limited long-term survival. In the fight against this deadly disease, there is still a long way to go.     

Advances in non-surgical management of primary liver cancer

Hepatocellular carcinoma(HCC) is the fifth most common cancer and the third most common cause of cancer-related death worldwide. There have been great improvements in the diagnosis and treatment of HCC in recent years, but the problems, including difficult diagnosis at early stage, quick progression, and poor prognosis remain unsolved. Surgical resection is the mainstay of the treatment for HCC. However, 70%-80% of HCC patients are diagnosed at an advanced stage when most are ineligible for potentially curative therapies such as surgical resection and liver transplantation. In recent years, non-surgical management for unrespectable HCC, such as percutaneous ethanol injection, percutaneous microwave coagulation therapy, percutaneous radiofrequency ablation, transcatheter arterial chemoembolization, radiotherapy, chemotherapy, biotherapy, and hormonal therapy have been developed. These therapeutic options, either alone or in combination, have been shown to control tumor growth, prolong survival time, and improve quality of life to some extent. This review covers the current status and progress of non-surgical management for HCC.     

Neoadjuvant chemoradiation in patients with pancreatic adenocarcinoma

In spite of the high mortality in pancreatic cancer, significant progress is being made. This review discusses multimodality therapy for patients with pancreatic cancer. Surgical therapy currently offers the only potential monomodal cure for pancreatic adenocarcinoma. However, only 10-20% of patients present with tumors that are amenable to resection, and even after resection of localized cancers, long-term survival is rare. The addition of chemoradiation therapy significantly increases median survival. To achieve long-term success in treating this disease it is therefore increasingly important to identify effective neoadjuvant/adjuvant multimodality therapies. Preoperative chemoradiation for potentially resectable pancreatic cancer has the following advantages: (1) neoadjuvant treatment would eliminate the delay of adjuvant treatment due to postoperative complications; (2) neoadjuvant treatment could avoid unnecessary surgery for patients with metastatic disease evident on restaging after neoadjuvant therapy; (3) down-staging after neoadjuvant therapy may increase the likelihood of negative surgical margins; and (4) neoadjuvant treatment could prevent peritoneal tumor cell implantation and dissemination caused during surgery. This review systematically summarizes the current status, controversies, and prospects of neoadjuvant treatment of pancreatic cancer.     

Hepatocellular carcinoma locoregional therapies: Outcomes and future horizons

Hepatocellular carcinoma (HCC) is the most common primary cancer of the liver and has an overall five-year survival rate of less than twenty percent. For patients with unresectable disease, evolving liver-directed locoregional therapies provide efficacious treatment across the spectrum of disease stages and via a variety of catheter-directed and percutaneous techniques. Goals of locoregional therapies in HCC may include curative intent in early-stage disease, bridging or downstaging to surgical resection or transplantation for early or intermediate-stage disease, and local disease control and palliation in advanced-stage disease. This review explores the outcomes of chemoembolization, bland embolization, radioembolization, and percutaneous ablative therapies. Attention is also given to prognostic factors related to each of the respective techniques, as well as future directions of locoregional therapies for HCC.