General treatment

2005440 Interventional therapy of hilar cholangio-carcinoma in type Ⅲ and Ⅳ.FAN Weijun(范卫君),et al.State Key Oncol Lab,Dept Radiol,Cancer Cen-ter,Sun Yat-Sen Univ,Guangzhou 510060.Chin J Ra-diol 2005;39(9):925-919.     

Drug treatment

2005144 Study of esomeprazole and rabeprazole on 24-hour intragastric acid control in healthy volunteers. ZHAN Xiaobao (湛先保), et al. Dept Gas-troenterol, Changhai Hosp, 2nd Milit Med Univ, Shanghai 200433. Chin J Dig, 2004; 24 (12): 711-714.     

Genetics and hepatitis C treatment: towards a personalized treatment?

Chronic HCV (hepatitis C virus) infection is an important cause of liver cirrhosis and hepatocellular carcinoma worldwide. HCV-related cirrhosis is the main indication for liver transplantation in our geographical area. Thus, treatment of this disease represents an important economical burden for the Health Care System. Current treatment of hepatitis C consists of pegylated interferon and ribavirin: only half of the patients achieve a sustained virological response after treatment. Factors related to the virus and the host influence response to treatment. Polymorphisms near the gene IL28B (encoding interferon-λ-3) have been recently identified as strong predictors of spontaneous HCV clearance in acute infection and of response to antiviral treatment in chronic hepatitis C. The aim of this article is to review the genetic studies that have emerged during the last months and its clinical implications, as well as to emphasize how Genetics is gaining importance in the management of liver diseases.     

Second-line treatment of advanced hepatocellular carcinoma: Time for more individualized treatment options?

Hepatocellular carcinoma (HCC) is the most frequently diagnosed primary tumor of the liver and is usually detected as advanced disease. It is an aggressive disease that often progresses rapidly when it fails to respond to treatment. As such, patients have limited opportunities to try different subsequent-line treatment regimens. In the last 5 years, the number of agents and/or regimens available for the treatment of advanced HCC has significantly increased, which has made treatment choices for this patient population increasingly complex. In the second-line setting, several phase III trials of regorafenib (RESORCE), ramucirumab (REACH/REACH-2), and cabozantinib (CELESTIAL) have demonstrated clinically meaningful survival benefits in patients with the disease. However, the median overall survival of patients with advanced HCC remains unchanged at approximately 12 mo from the start of systemic second-line therapy, with a limited duration of response. Evidence from the REACH/REACH-2 trials demonstrated for the first time that baseline alpha-fetoprotein (AFP) levels can be used as an identification factor to select those who are likely to benefit the most from ramucirumab treatment. Ramucirumab is both well tolerated and efficacious and has a clinically acceptable safety profile. Therefore, it should be considered an option for patients with AFP levels ≥ 400 ng/mL.     

Optimal treatment of dyslipidemia in high-risk patients: intensive statin treatment or combination therapy?

A recent update to the National Cholesterol Education Program's Adult Treatment Panel III guidelines suggests low-density lipoprotein cholesterol (LDL-C) goals of <70 mg/dL in very-high-risk patients and <100 mg/dL in high-risk patients. Currently available 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are not equal in their ability to lower LDL-C, and it is unlikely that the substantial LDL-C reductions that are often needed in high-risk persons can be achieved with starting doses of some of the older statins. Possible alternatives in such cases include the use of high-dose statin therapy, a more efficacious statin, or combination therapy. Recent clinical data have demonstrated a greater likelihood of coronary heart disease event reduction with aggressive statin therapy that lowers LDL-C in a robust fashion (>30%-40%) than with moderate therapy. Until data from ongoing trials of combination therapy are available, however, monotherapy with a potent statin should be initiated to lower LDL-C. Nonetheless, for residual elevation in triglycerides and/or reduced high-density lipoprotein cholesterol, adding a second agent (eg, fenofibrate, niacin) is a reasonable option.     

Advances in HIV treatment and prevention: Should treatment optimism lead to prevention pessimism?

Advances in HIV treatment have changed the natural history of HIV disease and improved the life of infected people. But, paradoxically, the transformation of a lethal disease into a chronic condition has lead many people to pessimism regarding the future of HIV prevention. Post-exposure prophylaxis and prophylaxis of vertical transmission have added new tools, although they do not change the main features of HIV prevention which still relies on safer drug use and safer sex. The role assigned to HIV testing started to change in some countries where it had not been encouraged; however the impact of these changes appears still very limited, except for prevention of vertical transmission. Recent developments should be placed in the whole historical perspective of HIV infection: after the early period of dramatic favourable changes (around 1990), positive changes in attitudes and behaviour have slowed down or even stabilized. Proofs of 'relapse' are, however, still tenuous. The impact of therapeutic changes is combined with the normalization process of HIV infection issues. In the general population, HIV infection seems a more remote personal and social concern and the perception of risk has decreased. The changes in the social context of prevention are more diverse. On one hand, some social norms renewed during the HIV era may have long-lasting effects. The acknowledgement of social and human rights of homosexuals and drug users, stimulated by the AIDS movement, has entered a long-term process and may continue to support preventive behaviours. On the other hand, the exceptionalist alliance which supported and stimulated the HIV policies is weakening. This process might be accelerated by improved therapeutic perspectives. The main challenge is the success of the integration of HIV prevention in broader public health policies (including prevention of STI transmission, family planning, health promotion, etc.) without losing advances in prevention strategies gained in the HIV/AIDS era.     

What is the best treatment?

The treatment of hepatitis C is expensive, difficult and arduous from the patient's perspective. It is similarly difficult for the clinician to decide who and when to treat. If hepatitis C is viewed from the liver's perspective we need only treat those patients who will develop the complications of chronic liver disease within their lifetimes. If we take a more holistic approach, then we have to consider the implications of being a carrier of a potentially transmissible blood borne virus on the patient themselves, their relationships, their families and their sense of wellbeing. There is now evidence of the large impact HCV has on quality of life and we have to consider extra hepatic manifestations of hepatitis C infection, possibly including the syndrome of 'brain fog' recently described. An additional factor that has to be considered in the decision to treat is whether patients perceive hepatitis C as a significant problem for themselves. For some patients, who have chaotic live styles, it is extremely difficult to get them to access healthcare. To then undergo the rigors and tribulations of hepatitis C therapy that is posing no current problem is unlikely to succeed. However, failure to engage these patients with therapy will lead to a significant proportion of them presenting with serious complications of chronic liver disease, with its attendant mortality, morbidity and cost. Underlying all these considerations is the tension between the costs of therapy and the benefits of therapy. Good arguments can be made in terms of cost-effectiveness for treating patients with a high likelihood of progressing to chronic liver disease and its complications. These arguments become much less persuasive when all patients are concerned.     

When is medical treatment futile?

A difficult ethical conundrum in clinical medicine is determining when to withdraw or withhold treatments deemed medically futile. These decisions are particularly complex when physicians have less experience with these discussions, when families and providers disagree about benefits from treatment, and when cultural disparities are involved in misunderstandings. This paper elucidates the concept of "medical futility," demonstrates the application of futility to practical patient care decisions, and suggests means for physicians to negotiate transitions from aggressive treatment to comfort care with patients and their families. Ultimately, respect of persons and beneficent approaches can lead to ethically and morally viable solutions.     

What choice of first-line treatment?

Treatment of advanced non-small cell lung cancer has evolved last years, until an individualized approach, notably according to patient characteristics, histology, and molecular profile of the tumor. So, the presence of EGFR mutations allows the administration of gefitinib in first line, with response rate around 70% and a progression-free survival around 12 months. If there is no EGFR mutation, the treatment consists in cytotoxic chemotherapy, according to histology. Indeed, non squamous carcinomas are accessible to a platin-pemetrexed doublet, and squamous carcinomas to another platin-based doublet. Besides, new molecular targets are identified, with corresponding targeted treatment. So, the EML4 - ALK translocation is accessible to a treatment by crizotinib, with response rate around 60-70%.     

Systemic treatment for unresectable hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is most commonly found in the context of liver cirrhosis and,in rare cases,in a healthy liver.Its prevalence has risen in recent years,particularly in Western nations,due to the increasing frequency of nonalcoholic fatty liver disease.Advanced HCC has a poor prognosis.For many years,the only proven therapy for unresectable HCC (uHCC) was sorafenib,a tyrosine kinase inhibitor.Recently,the synergistic effect of an immune checkpoint inhibitor,atezolizumab,and bevacizu...