Peipei Song

The management of hepatocellular carcinoma around the world: a comparison of guidelines from 2001 to 2011

In the past 10 years, many guidelines for hepatocellular carcinoma (HCC) have been published worldwide. To promote standard care for HCC, we systematically evaluated 17 current guidelines for HCC around the world, including 5 guidelines from the USA, 7 from Asia and 5 from Europe, according to the selection criteria of credibility influence and multi‐faceted. After a systematic evaluation, we found that these guidelines have both similarities and differences in terms of what organizations or bodies drafted the guidelines and the approach, applicability, content and recent updates of the guidelines as well as in terms of diagnostic and treatment algorithms. The differences could be attributed to various aetiological factors, high‐risk patients, health systems, health resources, medical technology, treatment choices and income levels in different countries. Besides, although the full implementation of guidelines could benefit clinicians, patients and authorities, there is still a gap between projected goals and implementation. The factors potentially influencing implementation are what organizations or bodies are drafting guidelines, content and emphasis, modification and consistency of guidelines. Comparative analysis suggested that countries pay close attention to targeted audiences, a basis in evidence, a basis in available resources, applicable patients and systematic evaluation when establishing and implementing domestic guidelines for HCC.

Biomarkers: Evaluation of Screening for and Early Diagnosis of Hepatocellular Carcinoma in Japan and China

Over the past few decades, the screening for and early diagnosis of hepatocellular carcinoma (HCC) has attracted attention worldwide, and especially in Asian countries such as Japan and China. Such approaches can help detecting HCC at an earlier stage when curable interventions can be offered to achieve long-term disease-free survival for patients. Biomarkers have been used to screen for and diagnose HCC in various countries. In Japan, the combined tests of des-γ-carboxyprothrombin (DCP) and α-fetoprotein (AFP) or Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3) have been shown to achieve a high level of sensitivity and specificity. These tests have routinely been used to screen for HCC and are covered by Japan’s national health insurance. Due to the routine practice of screening for HCC among high-risk patients, HCC nodules have been detected in the early stages in more than 60% of patients in Japan. In contrast, although several remarkable advances in the management of HCC have been made in China over the past few decades, most HCC patients still present with advanced-stage disease. AFP is the only serum biomarker that has widely been used to screen for and diagnose HCC in China. In recent years, several molecular biological studies have further investigated the clinical usefulness of DCP, and they have found that it may facilitate the screening for and diagnosis of HCC and assist with the assessment of HCC progression. DCP can serve as a biomarker to detect HCC in an early stage and facilitate definitive treatment. The wide implementation of DCP is expected, especially in China where 55% of HCC cases worldwide live.

Rare diseases, orphan drugs, and their regulation in Asia: Current status and future perspectives

Rare diseases are an important public health issue and a challenge to medical care. Specific legislation to encourage research of rare diseases and development of orphan drugs has been adopted in the United States (US), the European Union (EU), and elsewhere. In recent years, much progress has been made in some parts of Asia, including Japan, South Korea, and Taiwan, with the enactment of legislation and accompanying regulation of rare diseases and orphan drugs. China is also actively promoting the regulation of rare diseases and orphan drugs. We describe the current status of the regulation of rare diseases and orphan drugs in Asia and we comparatively analyze the regulation of rare diseases and orphan drugs worldwide in order to examine the challenges to and future perspectives on promoting research on rare diseases and development of orphan drugs in China and other Asian countries.

Controversies regarding and perspectives on clinical utility of biomarkers in hepatocellular carcinoma

The prevalence of hepatocellular carcinoma (HCC) worldwide parallels that of persistent infection with the hepatitis B virus (HBV) and/or hepatitis C virus (HCV). According to recommendations by the World Health Organization guidelines for HBV/HCV, alpha-fetoprotein (AFP) testing and abdominal ultrasound should be performed in routine surveillance of HCC every 6 mo for high-risk patients. These examinations have also been recommended worldwide by many other HCC guidelines over the past few decades. In recent years, however, the role of AFP in HCC surveillance and diagnosis has diminished due to advances in imaging modalities. AFP was excluded from the surveillance and/or diagnostic criteria in the HCC guidelines published by the American Association for the Study of Liver Diseases in 2010, the European Association for the Study of the Liver in 2012, and the National Comprehensive Cancer Network in 2014. Other biomarkers, including the Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3), des-γ-carboxyprothrombin, Dickkopf-1, midkine, and microRNA, are being studied in this regard. Furthermore, increasing attention has focused on the clinical utility of biomarkers as pre-treatment predictors for tumor recurrence and as post-treatment monitors. Serum and tissue-based biomarkers and genomics may aid in the diagnosis of HCC, determination of patient prognosis, and selection of appropriate treatment. However, further studies are needed to better characterize the accuracy and potential role of these approaches in clinical practice.

Optimal cut-off values for the homeostasis model assessment of insulin resistance (HOMA-IR) and pre-diabetes screening: Developments in research and prospects for the future

Diabetes mellitus (DM) appears to be increasing rapidly, threatening to reduce life expectancy for humans around the globe. The International Diabetes Federation (IDF) has estimated that there will be 642 million people living with the disease by 2040 and half as many again who will be not diagnosed. This means that pre-DM screening is a critical issue. Insulin resistance (IR) has emerged as a major pathophysiological factor in the development and progression of DM since it is evident in susceptible individuals at the early stages of DM, and particularly type 2 DM (T2DM). Therefore, assessment of IR via the homeostasis model assessment of IR (HOMA-IR) is a key index for the primary prevention of DM and is thus found in guidelines for screening of high-risk groups. However, the cut-off values of HOMA-IR differ for different races, ages, genders, diseases, complications, etc. due to the complexity of IR. This hampers the determination of specific cut-off values of HOMA-IR in different places and in different situations. China has not published an official index to gauge IR for primary prevention of T2DM in the diabetic and non-diabetic population except for children and adolescents ages 6-12 years. Hence, this article summarizes developments in research on IR, HOMA-IR, and pre-DM screening in order to provide a reference for optimal cut-off values of HOMA-IR for the diagnosis of DM in the Chinese population.

Targeting c-Met as a promising strategy for the treatment of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a severe condition that is found worldwide. Liver transplantation, surgical resection, and local-regional therapy such as transarterial chemoembolization have made great progress and play a dominant role in HCC management. However, the high frequency of tumor recurrence and/or metastasis after those treatments acquires systematic drug intervention. The approval of sorafenib, an agent that targets receptor tyrosine kinases (RTKs), as the first effective drug for systemic treatment of HCC represents a milestone in treatment of this disease. As a typical member of the RTK family, c-Met represents an intriguing target for cancer therapy. However, the role of the c-Met signal transduction pathway is less unambiguous in HCC pathology, giving rise to concerns about the feasibility of utilizing c-Met targeting approaches for HCC treatment. Recently, studies on des-γ-carboxy prothrombin, an abnormal cytokine secreted by HCC cells, by the current authors and other researchers have highlighted the critical role of c-Met signaling in HCC progression. This review takes a second look at the c-Met signal transduction pathway and discusses the possibility of targeting c-Met as a therapeutic strategy for HCC treatment.

The current management of cholangiocarcinoma: A comparison of current guidelines

Cholangiocarcinoma (CC) accounts for about 3% of all gastrointestinal tumors and is the second most common primary liver tumor. Quality guidelines on CC are needed to guide hepatobiliary surgeons. Here, current guidelines on CC were reviewed to provide useful information and suggestions to help institutes and organizations all around the world to draft better guidelines on CC. Literature databases were electronically searched to identify guidelines or consensus statements regarding CC published from 2002-2016. Nine guidelines were included in this review. Comparison of the current guidelines revealed several inconsistencies. Signs of conflicting views indicated a lack of high level evidence. More studies need to be conducted in areas of contention to help update the guidelines. Organizations and medical societies need to be encouraged to use standard evaluation measures, to restrict tumors to CC or iCC, pCC, or dCC specifically, to give recommendations in accordance with the equipment that is available for diagnosis and treatment in different counties, and to use an appropriate and consistent structure when establishing and drafting guidelines for CC.

Cost-Effectiveness of Bariatric Surgery for Type 2 Diabetes Mellitus: A Randomized Controlled Trial in China.

Abstract To compare the remission of type 2 diabetes mellitus (T2DM) through treatment with laparoscopic sleeve gastrectomy (LSG) or laparoscopic Roux-en-Y gastric bypass (LRYGB), and to analyze the cost-effectiveness of medical treatment, LSG, and LRYGB in T2DM patients (BMI ≥ 28). A 2-group randomized controlled trial was conducted at Diabetes Surgery Centre, Beijing Shijitan Hospital in Beijing, China. Subjects were 80 patients ages 16 to 65 years with a body mass index of 28 kg/m2 or more and duration of T2DM no more than 15 years. Subjects were randomly assigned (1:1) to undergo either LSG (n = 40) or LRYGB (n = 40) between February 3, 2011 and October 31, 2013. Of those patients, 72 (90%) were available at follow-up at 2 years. These patients included 34 (85%) who underwent LSG and 38 (95%) who underwent LRYGB. This study presents the follow-up data at 2 years, which compared LSG and LRYGB in T2DM patients. Partial remission and complete remission were determined, and weight loss, BMI, changes in abdominal circumference, cholesterol, and triglycerides were measured. The cost-effectiveness of each type of bariatric surgery was analyzed with a Markov simulation model that yielded quality-adjusted life-years (QALYs) and costs. From our analysis results, LSG and LRYGB are both have taken a great effect on the reduction of fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), and bodyweight in patients with T2DM. The cost-effectiveness ratios of medical treatment, LSG, and LRYGB respectively are 1589.02, 1028.97, and 1197.44 dollars per QALY. Our analysis indicates that LSG appear to provide a cost-effective method of T2DM treatment for the patients.

Perspectives on using des-γ-carboxyprothrombin (DCP) as a serum biomarker: facilitating early detection of hepatocellular carcinoma in China

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths in China. Evidence has shown that surgical resection and liver transplantation may offer the best potential for treating HCC but are only available to patients whose tumors are detected early. Over the past few decades, although a series of measures for standardized management of HCC has been implemented in China, most patients with HCC in China still present with advanced-stage disease, thus strategies to screen for and diagnose HCC at an earlier stage are urgently needed in China when curable interventions can be offered to achieve long-term disease-free survival for patients with HCC. In China, the serum biomarker α-fetoprotein (AFP) is considered a useful and feasible tool for HCC screening and early diagnosis. However, the sensitivity and specificity of AFP vary widely, and the total AFP is not always specific, especially when HCC is in its early stages. Globally, numerous studies have reported that the combination of des-γ-carboxyprothrombin (DCP) and AFP may have a higher sensitivity than AFP alone, and suggested DCP could also be used to assess the progression of HCC. However, DCP has not been approved in China until now. Differ from most of Western countries, people with HBV infection are the largest population at risk of developing HCC China. In order to assess the screening and diagnostic value of DCP in Chinese patients with HCC, a first large-scale, multi-center study was launched in China in 2012, results showed that DCP can help to detect HCC in its early stages and facilitate definitive treatment. The clinical use of DCP is urgently needed to facilitate early detection of HCC in China.

An updated systematic review of the evolution of ALPPS and evaluation of its advantages and disadvantages in accordance with current evidence

AbstractThe main obstacle to achieving an R0 resection after a major hepatectomy is inability to preserve an adequate future liver remnant (FLR) to avoid postoperative liver failure (PLF). Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is a novel technique for resecting tumors that were previously considered unresectable, and this technique results in a vast increase in the volume of the FLR in a short period of time. However, this technique continues to provoke heated debate because of its high mortality and morbidity.The evolution of ALPPS and its advantages and disadvantages have been systematically reviewed and evaluated in accordance with current evidence. Electronic databases (PubMed and Medline) were searched for potentially relevant articles from January 2007 to January 2016.ALPPS has evolved into various modified forms. Some of these modified techniques have reduced the difficulty of the procedure and enhanced its safety. Current evidence indicates that the advantages of ALPPS are rapid hypertrophy of the FLR, the feasibility of the procedure, and a higher rate of R0 resection in comparison to other techniques. However, ALPPS is associated with worse major complications, more deaths, and early tumor recurrence.Hepatobiliary surgeons should carefully consider whether to perform ALPPS. Some modified forms of ALPPS have reduced the mortality and morbidity of the procedure, but they cannot be recommended over the original procedure currently. Portal vein embolization (PVE) is still the procedure of choice for patients with a tumor-free FLR, and ALPPS could be used as a salvage procedure when PVE fails. More persuasive evidence needs to be assembled to determine whether ALPPS or two-stage hepatectomy (TSH) is better for patients with a tumor involving the FLR. Evidence with regard to long-term oncological outcomes is still limited. More meticulous comparative studies and studies of the 5-year survival rate of ALPPS could ultimately help to determine the usefulness of ALPPS. Indications and patient selection for the procedure need to be determined.