Hepatocellular Carcinoma Guidelines Research Articles

"Knowledge into action" – Exploration of an appropriate approach for constructing evidence-based clinical practice guidelines for hepatocellular carcinoma

With the development of evidence-based medicine (EBM), the concept of "transfer of current best evidence into clinical decision-making" has garnered substantial attention worldwide. As such a good tool, many clinical practice guidelines (CPGs) for hepatocellular carcinoma (HCC) have been published worldwide under the guide of current best evidence. Our study did a systematic evaluation of the current 17 guidelines for HCC worldwide, which found that the appropriate constructing approach is the most important factor that influences guidelines implementation. Three factors of organizations or bodies drafting the guideline, exploration for achieving current best evidence, and purpose of constructing evidence-based CPGs for HCC should be paid close attention to. In order to achieve the current best evidence and promote evidence-based CPGs to be widely accepted and fully implemented, we recommend to conduct a systematic approach with 4 steps of global guidelines assessment, systematic literature review, experts' consensus and draft implementation, as well as implementation evaluation and periodic update in constructing and implementing evidence-based CPGs for HCC.

Standardization of perioperative management on hepato-biliary-pancreatic surgery

Japan-China Joint Medical Workshop (2012) on standardization of perioperative management on hepato-biliary-pancreatic surgery was held by the Center for Medical Standards Research, IRCA-BSSA Group in Japan on April 15-16, 2012. Experts in the fields of surgery, anesthesia, pharmacy, and public health from 21 health institutions from Japan and China presented their research achievements and shared their medical experience of perioperative management on hepato-biliary-pancreatic surgery, which should facilitate building of guidelines for hepatocellular carcinoma and be expected to promote standardized management of liver cancer in Asia.

Changes of guidelines diagnosing hepatocellular carcinoma during the last ten-year period

Hepatocellular carcinoma (HCC) is the third most common cause of cancer deaths in the world. There have been many advances in the diagnosis of HCC during the last ten years, especially in the imaging techniques. The Korean Liver cancer study group (KLCSG), European Association for the Study of the Liver (EASL), American Association for the Study of Liver disease (AASLD), and Asian-Pacific Association for the Study of Liver (APASL) have made and changed the HCC guidelines with the advances in the imaging techniques and according to the results of the researches on HCC. We reviewed the changes of the imaging guidelines in HCC diagnosis according to the advances in the imaging techniques. Further studies will be necessary to resolve the controversies in the diagnosis of HCC smaller than 1 cm in size.

Treatment of recurrent hepatocellular carcinoma after liver transplantation

Liver transplantation (LT) is a curative treatment for localized hepatocellular carcinoma (HCC), but the recurrence rate after LT is about 10-20%, with a dismal prognosis. Little data exist as to the natural history, treatment outcome and optimal treatment of recurrent HCC after LT. We reviewed various treatment modalities given to patients with recurrent HCC after LT. Among 132 patients who underwent LT for localized HCC, we retrospectively reviewed medical records of 39 of the 132 patients who developed recurrent HCC after LT. We analyzed the clinical outcome of various treatment modalities and treatment-related adverse events. A total of 39 (29%) of the original 132 patients had recurrent HCC, most recurrences (82%) having occurred within 1 year after LT and involved extrahepatic lesions. Only seven patients had recurrent disease limited to the liver. The median overall survival from the initial treatment of all relapsed patients was 6.9 months. There were various initial treatment modalities, namely palliative systemic chemotherapy, trans-catheter arterial chemo-embolization/infusion (TACE/I), radiation therapy (RT), surgical resection and no treatment. The median overall survival was 9.5 months for first-line chemotherapy, including those who had prior local therapy, 6.3 months TACE/I and 6.9 months for RT. Various clinical approaches have been used to treat patients with recurrent HCC after LT in a clinical setting. More effective strategies and clinical guidelines for recurrent HCC following LT must be established.

Reply to Letter to the Editor from Prof Viroj Wiwanitkit, Bankok, Thailand

Dear Sir,Confounding causes of liver cancer such as alcohol or hepatitis have been controlled in our long-term prospective hepatocellular carcinoma (HCC) study [1]. The study was based on a well-characterized acute intermittent porphyria (AIP) population in northern Sweden [2]. Hepatitis B and C were rare in this age group in this sparsely populated northern part of Sweden. Hepatitis B and C virus tests were negative in all cases in the HCC study. Almost all subjects were well known by us regarding alcohol habits. No alcohol abuse was present amongst the cases. The cost-effectiveness of the surveillance was somewhat beyond the scope of this study. As mentioned in our article, the annual incidence of HCC in AIP gene carriers aged >50 years was 0.8%. As a comparison, the annual incidence of breast cancer amongst our general population of women in the same age group is 0.3%. Thus, the number needed to screen is three times higher to find one woman with breast cancer as compared with subjects with AIP and HCC in the mentioned age group. Surveillance programme for breast cancer in women is performed in some countries. The decision to enter a patient into a surveillance programme is dependent on the risk of HCC, which is related to the incidence of HCC. The increase in longevity is also of importance. Interventions that can be achieved at costs <$50 000 per year of life gained have been considered cost-effective [3]. Surveillance with ultrasonography once a year is the minor cost. The main cost is the treatment of HCC (radiofrequency ablation, surgical resection or, in few cases, liver transplantation). National guidelines for HCC in Sweden, including AIP, are in progress. Surveillance is considered cost-effective, but scientific evaluation is recommended based on empirical data. No conflict of interest was declared.

The changing scenario of hepatocellular carcinoma over the last two decades in Italy

This study investigates whether the aetiologic changes in liver disease and the improved management of hepatocellular carcinoma (HCC) have modified the clinical scenario of this tumour over the last 20 years in Italy. Retrospective study based on the analysis of the ITA.LI.CA (Italian Liver Cancer) database including 3027 HCC patients managed in 11 centres. Patients were divided into 3 groups according to the period of HCC diagnosis: 1987-1996 (year of the "Milano criteria" publication), 1997-2001 (year of release of the EASL guidelines for HCC), and 2002-2008. The significant changes were: (1) progressive patient ageing; (2) increasing prevalence of HCV infection until 2001, with a subsequent decrease, when the alcoholic aetiology increased; (3) liver function improvement, until 2001; (4) increasing "incidental" at the expense of "symptomatic" diagnoses, until 2001; (5) unchanged prevalence of tumours diagnosed during surveillance (around 50%), with an increasing use of the 6-month schedule; (6) favourable HCC "stage migration", until 2001; (7) increasing use of percutaneous ablation; (8) improving survival, until 2001. Over the last 20 years, several aetiologic and clinical features regarding HCC have changed. The survival improvement observed until 2001 was due to an increasing number of tumours diagnosed in early stages and in a background of compensated cirrhosis, and a growing and better use of locoregional treatments. However, the prevalence of early cancers and survival did not increase further in the last years, a result inciting national policies aimed at implementing surveillance programmes for at risk patients.

Knowledge of Hepatocellular Carcinoma Screening Guidelines and Clinical Practices Among Gastroenterologists

Screening of high-risk patients for hepatocellular carcinoma (HCC) may result in early diagnosis and improved outcomes. Our aim was to assess gastroenterologists' knowledge of HCC management guidelines established by the American Association for the Study of Liver Diseases (AASLD) and usual clinical practice. We surveyed gastroenterologists attending two gastroenterology board review courses regarding their knowledge of HCC screening guidelines and usual practice of screening for HCC. Practices were compared and adherence to the 2005 published HCC guidelines was assessed. The median age of gastroenterology attending physicians (n = 160) was 41 years, and 75% were men with a median of 11.5 years of practice. A total of 79% of respondents correctly identified the high-risk patients who qualify for HCC screening. Most gastroenterologists correctly identified the screening methods (88.5%) and screening interval (98%). Among those who knew guideline recommendations (i.e., correct identification and certainty of guideline recommendations), 100% reported that they followed the guideline recommendation in their own practices. Regarding the management of abnormal test, 31% of gastroenterologists did not identify that referral for liver transplantation is the recommended management strategy for small HCC in a Child B patient with cirrhosis. The number of years in clinical practice (p = 0.30) and involvement in a malpractice suit (p = 0.34) did not affect the practice patterns. Most gastroenterologists correctly identified the common high-risk scenarios, methods, and interval of HCC screening as recommended by AASLD. Gastroenterologists who knew the HCC guidelines applied them in their own practice. However, approximately one-quarter do not know the appropriate management of a positive result, thereby likely hampering the overall effectiveness of screening.

Practice guidelines for management of hepatocellular carcinoma 2009

Hepatocellular carcinoma (HCC) is a major cancer in Korea, typically has a poor prognosis, and constitutes the majority of primary hepatic malignancies. It is the number one cause of death among people in their 50s in Korea. The five-year survival rate of liver cancer is poor; at 18.9%. Efforts to increase the survival rate through early diagnosis of HCC and optimal treatments are keenly needed. Western guideline for the management of HCC were developed, but these guidelines are somewhat unsuitable for Korean patients. Thus, the Korean Liver Cancer Study Group (KLCSG) and the National Cancer Center (NCC), Korea jointly produced the Clinical Practice Guidelines for HCC for the first time in Korea in 2003. Owing to medical advances over the following six years, diagnosis and treatment of HCC has changed considerably. As more national and foreign data are accumulated, KLCSG and NCC, Korea recently revised the Clinical Practice Guidelines for HCC. Forty or more specialists in the field of hepatology, general surgery, radiology and radiation oncology participated, and meticulously reviewed national and foreign papers, and collected opinions through advisory committee conferences. These multidisciplinary, evidence-based guidelines summarized diagnosis, surgical resection, liver transplantation, local treatments, transarterial chemoembolization, radiation therapy, chemotherapy, preemptive antiviral treatments, and response evaluation of HCC. These Korean guidelines are expected to be useful for clinical management of and research on HCC.

Development of evidence‐based clinical guidelines for the diagnosis and treatment of hepatocellular carcinoma in Japan

The Clinical Practice Guidelines for Hepatocellular Carcinoma (HCC), the first evidence-based guidelines for the treatment of HCC in Japan, were compiled by an expert panel supported by the Japanese Ministry of Health, Labour, and Welfare. This set of guidelines covers six research fields: prevention, diagnosis and surveillance, surgery, chemotherapy, transarterial chemoembolization, and percutaneous local ablation therapy. A systematic review of the English medical literature on HCC was performed, and a total of 7192 publications were extracted, mainly from MEDLINE (1966-2002). After the second selection, 334 articles were adopted for the guidelines to form 58 pairs of research questions and recommendations. For the users' convenience, practical algorithms for the surveillance and treatment of HCC were also created, which were based on evidence from the selected articles forthe guidelines and modified according to the current status of medical practice in Japan, where liver resection for HCC is regarded as safe with less than 1% mortality and cadaveric donors for liver transplantation are extremely difficult to obtain. The formation of the guidelines and the outline of their contents are described. The Japanese HCC guidelines may be useful in decision making at every clinical step, both for patients and physicians. Although the main users of these guidelines are assumed to be Japanese physicians, the accumulated evidence and interpretation in the guidelines may attract universal attention.