Surveillance for early diagnosis of hepatocellular carcinoma: How best to do it?

Surveillance for hepatocellular carcinoma(HCC)is considered a standard of care for patients with chronic liver disease who are at risk of developing this malignancy.Several studies have shown that surveillance can improve the prognosis of patients diagnosed with HCC through an increased likelihood of application of curative or effective treatments.Repetition of liver ultrasonography(US)every 6 mo is the recommended surveillance program to detect early HCCs,and a positive US has to entrain a well-defined recall policy based on contrast-enhanced,dynamic radiological imaging or biopsy for the diagnosis of HCC.Although HCC fulfills the accepted criteria regarding cost-effective cancer screening and surveillance,the implementation of surveillance in clinical practice is defective and this has a negative impact on the cost-effectiveness of the procedure.Education of both physicians and patients is of paramount importance in order to improve the surveillance application and its benefits in patients at risk of HCC.The promotion of specific educational programs for practitioners,clinicians and patients is instrumental in order to expand the correct use of surveillance in clinical practice and eventually improve HCC prognosis.     

Surveillance for hepatocellular carcinoma in chronic viral hepatitis: Is it time to personalize it?

Surveillance with abdominal ultrasound with or without alpha-fetoprotein is recommended by clinical practice guidelines for patients who are considered to be at risk of developing hepatocellular carcinoma (HCC), including those with cirrhosis, advanced fibrosis and special subgroups of chronic hepatitis B (CHB). Application of the standard surveillance strategy to all patients with chronic liver disease (CLD) with or without cirrhosis imposes major sustainability and economic burdens on healthcare systems. Thus, a number of HCC risk scores were constructed, mainly from Asian cohorts, to stratify the HCC prediction in patients with CHB. Similarly, even if less than for CHB, a few scoring systems were developed for chronic hepatitis C patients or cirrhotic patients with CLD of different etiologies. Recently, a few newsworthy HCC-risk algorithms were developed for patients with cirrhosis using the combination of serologic HCC markers and clinical parameters. Overall, the HCC risk stratification appears at hand by several validated multiple score systems, but their optimal performance is obtained only in populations who show highly homogenous clinic-pathologic, epidemiologic, etiologic and therapeutic characteristics and this limitation poses a major drawback to their sustainable use in clinical practice. A better understanding of the dynamic process driving the progression from CLD to HCC derived from studies based on molecular approaches and genetics, epigenetics and liquid biopsy will enable the identification of new biomarkers to define the individual risk of HCC in the near future, with the possibility to achieve a real and cost/effective personalization of surveillance.     

Treatment for occult hepatocellular carcinoma: does it offer survival advantages over symptom-driven treatment?

Objective: In order to claim a benefit of screen-based diagnosis for asymptomatic individuals, treatment of occult disease needs to offer survival advantages compared to the treatment of symptomatic disease, yet information on this issue is scarce with regard to hepatocellular carcinoma (HCC) screening.

Methods: A total of 3353 treatment-naïve, consecutive, newly diagnosed HCC patients [age: 57.9?±?10.3, male: 2,689 (80.2%), hepatitis B virus: 2555 (76.2%)], diagnosed between 2010 and 2013 were analyzed. Data on the mode of detection was prospectively collected at the time of HCC diagnosis and was used to group patients into occult or symptomatic cases.

Results: Overall, 643 (19.2%) patients were symptomatic cases. The proportion of patients undergoing resection, radiofrequency ablation or transplantation were lower in symptomatic cases than occult cases (20.8 vs. 56.2%, p?p?Conclusion: Treatment of occult disease offered a survival benefit to patients over symptomatic cases. These data support screening practices for asymptomatic individuals to diagnose occult HCC.     

Surveillance for early diagnosis of hepatocellular carcinoma: is it effective in intermediate/advanced cirrhosis?

OBJECTIVES: Surveillance of cirrhotic patients for early diagnosis of hepatocellular carcinoma (HCC), based on ultrasonography and alpha-fetoprotein (AFP) measurement, is widely used. Its effectiveness depends on liver function, which affects the feasibility of treatments and cirrhosis-related mortality. We assessed whether patients with intermediate/advanced cirrhosis benefit from surveillance. METHODS: We selected 468 Child-Pugh class B and 140 class C patients from the ITA.LI.CA database, including 1,834 HCC patients diagnosed from January 1987 to December 2004. HCC was detected in 252 patients during surveillance (semiannual 172, annual 80 patients; group 1) and in 356 patients outside surveillance (group 2). Survival of surveyed patients was corrected for the estimated lead time. RESULTS: Child-Pugh class B: cancer stage (P < 0.001) and treatment distribution (P < 0.001) were better in group 1 than in group 2. The median (95% CI) survivals were 17.1 (13.5-20.6) versus 12.0 (9.4-14.6) months and the survival rates at 1, 3, and 5 yr were 60.4%versus 49.2%, 26.1%versus 16.1%, and 10.7%versus 4.3%, respectively (P= 0.022). AFP, gross pathology, and treatment of HCC were independent prognostic factors. Child-Pugh class C: cancer stage (P= 0.001) and treatment distribution (P= 0.021) were better in group 1 than in group 2. Nonetheless, median survival did not differ: 7.1 (2.1-12.1) versus 6.0 (4.1-7.9) months (P= 0.740). CONCLUSIONS: These results suggest surveillance be offered to class B patients and maintained for class A patients who migrate to the subsequent class. Surveillance becomes pointless in class C patients probably because the poor liver function adversely affects the overall mortality and HCC treatments.     

Pacing for hypertrophic obstructive cardiomyopathy does it work?

Sixty-nine years old lady presented with sudden cardiac arrest, she was found to have hypertrophic obstructive cardiomyopathy, she refused septal myomectomy and had a dual chamber ICD implanted, she was put on right ventricular apical pacing with short AV interval, after pacing her max pressure gradient across left ventricular out flow tract (LVOT) dropped from 117 mmHg to 21 mmHg and her symptoms much improved over a follow up period of 1 year.     

Screening for lung cancer: it works, but does it really work?

After the publication of the NLST (National Lung Screening Trial) results, physicians will be faced with whether to begin ordering low-dose computed tomography (LDCT) of the chest to screen for lung cancer in patients with a history of tobacco use. Despite the encouraging reduction in deaths observed by using LDCT in the NLST study population, recommending adoption of lung cancer screening in general practice is premature. Lessons learned from prostate and breast cancer screening should remind us that the reductions in deaths expected with screening are unfortunately not as readily achievable as initially believed. Furthermore, the potential harms of false-positive findings on chest computed tomography are very real. The morbidity and even mortality associated with invasive diagnostic testing and surgical resection due to false- and true-positive findings on computed tomography are likely to increase when the approach taken in the NLST is applied in non-specialty care settings and among the population at highest risk, namely, those with smoking-related comorbid conditions. Although the NLST results are perhaps encouraging, they do not tell us enough that we can be sure that patients who undergo LDCT in an attempt to find early-stage lung cancer will have more benefit than harm.     

Liver transplantation for hepatocellular carcinoma: racial disparities?

Liver transplantation for patients with early-stage hepatocellular cancer evidently represents an extremely effective treatment as compared to other modalities, at least by one analysis of a cancer database. However, less than one-fourth of the apparently acceptable candidates receive this treatment and African Americans are underrepresented in this group. The cause of these results, however, remains obscure with the need for a more in-depth confirmation of these findings readily apparent.     

Clopidogrel: How good is it and how does it work?

Until recently, long-term antiplatelet therapy for the treatment and prevention of the complications of atherothrombotic disease was limited to aspirin. Although an incredibly costeffective therapy, in placebo-controlled clinical trials approximately 75% of patients at risk continue to experience thrombotic events despite chronic aspirin therapy. The availability of the thienopyridines, in particular clopidogrel, represents an important addition to the physician’s armamentarium. A number of clinical trials have confirmed the efficacy of the combination of clopidogrel and aspirin therapy compared with aspirin alone, with multiple other important largescale clinical trials currently ongoing. The exact mechanism of this benefit is still being elucidated but is clearly related to the inhibition of the many consequences of platelet activation—vascular inflammation, endothelial dysfunction, and localized angiogenesis/mitogenesis—and not just aggregation.     

Pneumococcal vaccination in adults: does it really work?

The universal burden of pneumococcal disease is high. As pneumococcal capsular antigens induce serotype specific antibodies, both the available vaccines (polysaccharide and polysaccharide conjugated) are able to produce serological response. However, there is reasonable skepticism about the effectiveness and efficacy of the 23-valent polysaccharide vaccine, especially in the elderly and in immunocompromised adults. Results from numerous studies are conflicting but the more recent data suggest that polysaccharide vaccine raises inadequate protection against non-bacteremic pneumonia, while the benefit against invasive pneumococcal disease in high-risk population is uncertain. On the contrary, conjugate vaccine, -originally indicated only for infants and young children- appears to be highly effective but it does not cover the tremendous diversity of pneumococcal serotypes being able to cause disease in adults. Despite this, there is growing evidence that conjugate vaccines, due to their superior immunogenicity, could also be offered for adult vaccination, but still there are certain issues that warrant further investigation.     

Brief physician- and nurse practitioner-delivered counseling for high-risk drinkers: does it work?

BACKGROUND: There is a need for primary care providers to have brief effective methods to intervene with high-risk drinkers during a regular outpatient visit. OBJECTIVE: To determine whether brief physician- and nurse practitioner-delivered counseling intervention is efficacious as part of routine primary care in reducing alcohol consumption by high-risk drinkers. METHODS: Academic medical center-affiliated primary care practice sites were randomized to special intervention or to usual care. From a screened population of 9772 patients seeking routine medical care with their primary care providers, 530 high-risk drinkers were entered into the study. Special intervention included training providers in a brief (5- to 10-minute) patient-centered counseling intervention, and an office support system that screened patients, cued providers to intervene, and made patient education materials available. The primary outcome measures were change in alcohol use from baseline to 6 months as measured by weekly alcohol consumption and frequency of binge drinking episodes. RESULTS: Participants in the special intervention and usual care groups were similar on important background variables and potential confounders except that special intervention participants had significantly higher baseline levels of alcohol usage (P = .01). At 6-month follow-up, in the 91% of the cohort who provided follow-up information, alcohol consumption was significantly reduced when adjusted for age, sex, and baseline alcohol usage (special intervention, -5.8 drinks per week; usual care, -3.4 drinks per week; P = .001). CONCLUSIONS: This study provides evidence that screening and very brief (5- to 10-minute) advice and counseling delivered by a physician or nurse practitioner as part of routine primary care significantly reduces alcohol consumption by high-risk drinkers.     

Diabetes mellitus:atrueindependent risk factor for hepatocellular carcinoma?

BACKGROUND:Diabetes mellitus(DM)is thought to be associated with an increased risk of hepatocellular carcinoma(HCC)in some published studies.However,can we draw the conclusion that DM is atrueindependent risk factor for HCC based on these references? DATA SOURCES:MEDLINE and PubMed searches were conducted for published studies(between January 1966 and June 2009)to identify relevant articles using the keywords diabetes,insulin resistanceandhepatocellular carcinoma,includingprimary liver cancer.Because of the...