There have been major advances in the armamentarium for hepatocellular carcinoma (HCC) since the last official update of the Barcelona Clinic Liver Cancer prognosis and treatment strategy published ...in 2018. Whilst there have been advances in all areas, we will focus on those that have led to a change in strategy and we will discuss why, despite being encouraging, data for select interventions are still too immature for them to be incorporated into an evidence-based model for clinicians and researchers. Finally, we describe the critical insight and expert knowledge that are required to make clinical decisions for individual patients, considering all of the parameters that must be considered to deliver personalised clinical management.
This study prospectively evaluates the accuracy of contrast‐enhanced ultrasound (CEUS) and dynamic magnetic resonance imaging (MRI) for the diagnosis of nodules 20 mm or smaller detected during ...ultrasound (US) surveillance. We included 89 patients with cirrhosis median age, 65 years; male 53, hepatitis C virus 68, Child‐Pugh A 80 without prior hepatocellular carcinoma (HCC) in whom US detected a small solitary nodule (mean diameter, 14 mm). Hepatic MRI, CEUS, and fine‐needle biopsy (gold standard) (FNB) were performed at baseline. Non‐HCC cases were followed (median 23 months) by CEUS/3 months and MRI/6 months. FNB was repeated up to 3 times and on detection of change in aspect/size. Intense arterial contrast uptake followed by washout in the delayed/venous phase was registered as conclusive for HCC. Final diagnoses were: HCC (n = 60), cholangiocarcinoma (n = 1), and benign lesions (regenerative/dysplastic nodule, hemangioma, focal nodular hyperplasia) (n = 28). Sex, cirrhosis cause, liver function, and alpha‐fetoprotein (AFP) levels were similar between HCC and non‐HCC groups. HCC patients were older and their nodules significantly larger (P < 0.0001). First biopsy was positive in 42 of 60 HCC patients. Sensitivity, specificity, and positive and negative predictive values of conclusive profile were 61.7%, 96.6%, 97.4%, and 54.9%, for MRI, 51.7%, 93.1%, 93.9%, and 50.9%, for CEUS. Values for coincidental conclusive findings in both techniques were 33.3%, 100%, 100%, and 42%. Thus, diagnosis of HCC 20 mm or smaller can be established without a positive biopsy if both CEUS and MRI are conclusive. However, sensitivity of these noninvasive criteria is 33% and, as occurs with biopsy, absence of a conclusive pattern does not rule out malignancy. These results validate the American Association for the Study of Liver Disease (AASLD) guidelines. (HEPATOLOGY 2007.)
Background
Magnetic resonance enterography (MRE) is an accurate examination for assessing activity in Crohn’s disease (CD). Various MRE indices have been developed for that purpose, but have not been ...directly compared. The aim of the study was to compare the diagnostic accuracy of three MRE indices for detecting and grading disease activity in CD, using endoscopy as gold standard.
Methods
MRE and ileocolonoscopies performed within 1 month in 43 patients with CD were analyzed. The magnetic resonance index of activity (MaRIA), Clermont, and London indices for each colonic segment and the terminal ileum were calculated. Simplified endoscopy score for CD (SES-CD) was considered the gold standard.
Results
Two hundred and twenty-four intestinal segments were included in the analysis. According to the established cut-off points for detecting active disease using MaRIA, Clermont, and London indices, the sensitivity of each index was 0.88, 0.89, and 0.71, and the specificity was 0.97, 0.78, and 0.99, respectively. The sensitivity for detecting ulcerations was 0.90 and 0.83 for the MaRIA and Clermont indices, respectively, with a specificity of 0.91 and 0.89. The AUROC curve for the MaRIA, Clermont, and London indices for detecting active disease was 0.92, 0.84, and 0.85, and for detecting ulcerations was 0.90 for the MaRIA, and 0.86 for Clermont index.
Conclusions
The three MRE-based indices evaluated in the current study have high diagnostic accuracy for assessment of disease activity. The MaRIA index has the best operational characteristics for detecting not only disease activity but also for grading severity, which supports its use in clinical studies and clinical practice.
Recent advancements have improved the management of patients with liver cancer. Results of studies have informed how to stage and decide the optimal treatment option for each patient with an adequate ...balance between risks and benefits. The Barcelona Clinic Liver Cancer (BCLC) staging and treatment strategy has been widely endorsed for this purpose. This is not a rigid system: One of the key aspects in the management of patients is the optimal timing for systemic treatment initiation and for declaring tumor progression and/or treatment failure. Some patients at intermediate or even early stage may be considered for systemic therapy as options of higher priority may have failed or may not be feasible. Sorafenib is the sole systemic agent that has shown efficacy in phase 3 trials. Other agents (sunitinib, brivanib, linifanib, everolimus, ramucirumab) have failed in terms of safety and/or survival benefit. Optimal sorafenib administration and adequate adherence of the patients are crucial requirements to obtain the benefits of the drug. Because development of adverse events has been shown to correlate with better outcome, careful dose adjustments should be in place while avoiding unnecessary treatment interruption. Furthermore, recent studies have shown that progression at imaging may not translate in poor prognosis and that treatment beyond progression may be considered if there is no option for a second-line research trial.In this review, the authors examine all of the controversial aspects that affect treatment initiation and maintenance, how response to treatment should be evaluated, and define the needs that are faced by current research.
To investigate genetics, electrophysiology, and clinical course of KCNV2-associated retinopathy in a cohort of children and adults.
This was a multicenter international clinical cohort study.
Review ...of clinical notes and molecular genetic testing. Full-field electroretinography (ERG) recordings, incorporating the international standards, were reviewed and quantified and compared with age and recordings from control subjects.
In total, 230 disease-associated alleles were identified from 117 patients, corresponding to 75 different KCNV2 variants, with 28 being novel. The mean age of onset was 3.9 years old. All patients were symptomatic before 12 years of age (range, 0-11 years). Decreased visual acuity was present in all patients, and 4 other symptoms were common: reduced color vision (78.6%), photophobia (53.5%), nyctalopia (43.6%), and nystagmus (38.6%). After a mean follow-up of 8.4 years, the mean best-corrected visual acuity (BCVA ± SD) decreased from 0.81 ± 0.27 to 0.90 ± 0.31 logarithm of minimal angle of resolution. Full-field ERGs showed pathognomonic waveform features. Quantitative assessment revealed a wide range of ERG amplitudes and peak times, with a mean rate of age-associated reduction indistinguishable from the control group. Mean amplitude reductions for the dark-adapted 0.01 ERG, dark-adapted 10 ERG a-wave, and LA 3.0 30 Hz and LA3 ERG b-waves were 55%, 21%, 48%, and 74%, respectively compared with control values. Peak times showed stability across 6 decades.
In KCNV2-associated retinopathy, full-field ERGs are diagnostic and consistent with largely stable peripheral retinal dysfunction. Report 1 highlights the severity of the clinical phenotype and established a large cohort of patients, emphasizing the unmet need for trials of novel therapeutics.
•The current study established the largest and most characterized cohort of molecularly confirmed patients with KCNV2-associated retinopathy.•Report 1 highlights the genetic background, evidence of electroretinography stability over a broad age range, and the severe phenotype of the disease.
Objectives
To describe the different morphological enhancement patterns of focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA) in the hepatobiliary phase (HBP) of gadoxetic acid-enhanced ...MRI (Gd-EOB-DTPA MRI) and to determine their added value in their differential diagnosis.
Methods
A retrospective analysis of imaging findings in 185 benign hepatocellular lesions (154 FNH; 31 HCA) in 108 patients who underwent Gd-EOB-DTPA MRI was performed by two independent reviewers. Six patterns on HBP were recorded: 1) homogeneous enhancement; 2) peripheral ring-like enhancement with hypointense central core; 3) peripheral ring-like enhancement with hyperintense central core; 4) central core enhancement with hypointense periphery; 5) heterogeneous enhancement; and 6) the absence of enhancement.
Results
Peripheral ring-like enhancement with hypointense central core and peripheral ring-like enhancement with hyperintense central core showed the highest specificity for the diagnosis of FNH (100% and 96.8%, respectively). The absence of enhancement and central core enhancement with hypointense periphery were only present in 0.6% and 1.9% of FHN, respectively. All other patterns were observed with similar frequencies in FNH (22.1% to 26.6%). Six HCA showed contrast uptake on the HBP: homogeneous (6.5%), peripheral ring-like enhancement with hyperintense central core (3.2%) and heterogeneous (9.7%).
Conclusion
Both FNH and HCA may demonstrate enhancement in the HBP of Gd-EOB-DTPA MRI, limiting its specificity. A significant improvement in specificity can be achieved by the evaluation of morphological enhancement patterns: Peripheral ring-like enhancement with hypointense or hyperintense central core was highly specific for FNH diagnosis. On the other hand, the absence of HBP enhancement makes the diagnosis of FNH unlikely.
This study assesses the magnetic resonance (MR) features of intrahepatic cholangiocarcinoma (ICC) in patients with cirrhosis with specific analysis of the contrast enhancement pattern. ...Cholangiocarcinoma may show increased contrast uptake in the arterial phase, and, if washout in the delayed venous phase were to be detected, the noninvasive diagnostic criteria proposed in the American Association for the Study of Liver Diseases guidelines would be refuted. We reviewed the MR findings of 25 patients with cirrhosis with 31 histologically confirmed ICC nodules. Signal intensity on basal T1‐weighted and T2‐weighted images and characteristics of enhancement after contrast administration on arterial, portal, and delayed phase were registered. Enhancement pattern was defined according to the behavior of the lesions in each phase, and dynamic pattern was described according to the progression of enhancement throughout the different phases. The most frequent pattern displayed by ICC was a progressive contrast uptake (80.6%). Stable contrast enhancement was registered in 19.4%. None of the ICCs showed a washout pattern, a profile that is specific for hepatocellular carcinoma (HCC). The ICC dynamic behavior differed significantly according to tumor size: progressive enhancement pattern was the most frequent (20 of 25 cases) in lesions larger than 20 mm, whereas the stable pattern was mainly identified in nodules smaller than 20 mm. The most characteristic MR contrast pattern in ICC in cirrhosis is a progressive contrast uptake throughout the different phases, whereas contrast washout at delayed phases is not observed. Because stable enhancement pattern without washout also can be registered in small HCC nodules, the evaluation of delayed phase is mandatory for a proper nodule characterization. If washout is not registered, a biopsy should be mandatory for diagnosis. (HEPATOLOGY 2009.)
Generalized lymphatic anomaly (GLA) is a vascular disorder characterized by diffuse or multifocal lymphatic malformations (LMs). The etiology of GLA is poorly understood. We identified four distinct ...somatic
variants (Glu542Lys, Gln546Lys, His1047Arg, and His1047Leu) in tissue samples from five out of nine patients with GLA. These same
variants occur in
-related overgrowth spectrum and cause hyperactivation of the PI3K-AKT-mTOR pathway. We found that the mTOR inhibitor, rapamycin, prevented lymphatic hyperplasia and dysfunction in mice that expressed an active form of
(His1047Arg) in their lymphatics. We also found that rapamycin reduced pain in patients with GLA. In conclusion, we report that somatic activating
mutations can cause GLA, and we provide preclinical and clinical evidence to support the use of rapamycin for the treatment of this disabling and deadly disease.
Haloferaxmediterranei is a haloarchaeon of high interest in biotechnology because it produces and mobilizes intracellular polyhydroxyalkanoate (PHA) granules during growth under stress conditions ...(limitation of phosphorous in the culture media), among other interesting metabolites (enzymes, carotenoids, etc.). The capability of PHA production by microbes can be monitored with the use of staining-based methods. However, the staining of haloarchaea cells is a challenging task; firstly, due to the high ionic strength of the medium, which is inappropriate for most of dyes, and secondly, due to the low permeability of the haloarchaea S-layer to macromolecules. In this work, Haloferax mediterranei is used as a halophilic archaeon model to describe an optimized protocol for the visualization and analysis of intracellular PHA granules in living cells. The method is based on double-fluorescence staining using Nile red and SYBR Green by confocal fluorescence microscopy. Thanks to this method, the capability of PHA production by new haloarchaea isolates could be easily monitored.
Display omitted
•The risk of HCC in patients with HCV cirrhosis treated with DAAs persists despite viral cure.•The presence of indeterminate nodules before starting DAA is associated with a 3 times ...greater risk of HCC.•A time association between DAA therapy and developing HCC reflects increased short-term HCC risk.•DAA therapy elicits a mechanism that primes the emergence of HCC early during follow-up.
Despite direct-acting antivirals being highly effective at eradicating hepatitis C virus infection, their impact on the development of hepatocellular carcinoma (HCC) remains controversial. We analyzed the clinical and radiological outcome of cirrhotic patients treated with interferon-free regimens to estimate the risk of developing HCC.
This was a retrospective multicenter study focusing on cirrhotic patients treated with direct-acting antivirals until December 2016. Clinical and radiologic characteristics were collected before the start of antiviral therapy, at follow-up and at HCC development. Diagnosis of HCC was centrally validated and its incidence was expressed as HCC/100 person-years.
A total of 1,123 patients were included (60.6% males, 83.8% Child-Pugh A) and 95.2% achieved a sustained virologic response. Median time of follow-up was 19.6 months. Seventy-two patients developed HCC within a median of 10.3 months after starting antiviral treatment. HCC incidence was 3.73 HCC/100 person-years (95% CI 2.96–4.70). Baseline liver function, alcohol intake and hepatic decompensation were associated with a higher risk of HCC. The relative risk was significantly increased in patients with non-characterized nodules at baseline 2.83 (95% CI 1.55–5.16) vs. absence of non-characterized nodules. When excluding these patients, the risk remained increased.
These data expose a clear-cut time association between interferon-free treatment and HCC. The mechanisms involved in the increased risk of HCC emergence in the short term require further investigation.
In this cohort of cirrhotic patients, interferon-free therapies achieved a high rate of sustained virologic response (>95%); however, we reported a risk of de novo hepatocellular carcinoma of 3.73 per 100 person-years and a clear-cut time association with antiviral therapy. The time association between starting direct-acting antivirals and developing hepatocellular carcinoma, together with the association with the presence of non-characterized nodules at baseline ultrasound, suggests that antiviral therapy elicits a mechanism (probably immune-related) that primes the growth and clinical recognition of hepatocellular carcinoma early during follow-up. As a result, short-term liver cancer risk is significantly increased.
PDF
