Surveillance for hepatocellular carcinoma in chronic liver disease:Evidence and controversies

Primary liver cancer is the sixth most common cancer in the world and the third cause of cancer-related death.Hepatocellular carcinoma(HCC)represents more than90%of primary liver cancers and generally occurs in patients with underlying chronic liver disease such as viral hepatitis,hemochromatosis,primary biliary cirrhosis and non-alcoholic steatohepatitis.Especially cirrhotic patients are at risk of HCC and regular surveillance could enable early detection and therapy,with potentially improved outcome.We here summarize existing evidence for surveillance including ultrasound,other radiological modalities and various serum biomarkers,and current international guideline recommendations for surveillance.Ultrasound andα-fetoprotein(alone or in combination)are most frequently used for surveillance,but their sensitivities and specificities are still far from perfect,and evidence for surveillance remains weak and controversial.Various other potential surveillance tools have been tested,including serum markers as des-carboxyprothrombin,lectin-boundα-fetoprotein,and(most recently)circulating TIE2-expressing monocytes,and radiological investigations such as computed tomographyscan or magnetic resonance imaging-scan.Although early results appear promising,these tools have generally been tested in diagnostic rather than surveillance setting,and in most cases,no detailed information is available on their cost-effectiveness.For the near future,it remains important to define those patients with highest risk of HCC and most benefit from surveillance,and to restrict surveillance to these categories.

Retrograde-viewing device improves adenoma detection rate in colonoscopies for surveillance and diagnostic workup

AIM:To determine which patients might benefit most from retrograde viewing during colonoscopy through subset analysis of randomized,controlled trial data.METHODS:The Third Eye Retroscope Randomized Clinical Evaluation(TERRACE) was a randomized,controlled,multicenter trial designed to evaluate the efficacy of a retrograde-viewing auxiliary imaging device that is used during colonoscopy to provide a second video image which allows viewing of areas on the proximal aspect of haustral folds and flexures that are difficult to see with the colonoscope's forward view.We performed a post-hoc analysis of the TERRACE data to determine whether certain subsets of the patient population would gain more benefit than others from use of the device.Subjects were patients scheduled for colonoscopy for screening,surveillance or diagnostic workup,and each underwent same-day tandem examinations with standard colonoscopy(SC) and Third Eye colonoscopy(TEC),randomized to SC followed by TEC or vice versa.RESULTS:Indication for colonoscopy was screening in 176/345 subjects(51.0%),surveillance after previous polypectomy in 87(25.2%) and diagnostic workup in 82(23.8%).In 4 subjects no indication was specified.Previously reported overall results had shown a net additional adenoma detection rate(ADR) with TEC of 23.2% compared to SC.Relative risk(RR) of missing adenomas with SC vs TEC as the initial procedure was 1.92(P = 0.029).Post-hoc subset analysis shows additional ADRs for TEC compared to SC were 4.4% for screening,35.7% for surveillance,55.4% for diagnostic and 40.7% for surveillance and diagnostic combined.The RR of missing adenomas with SC vs TEC was 1.11(P = 0.815) for screening,3.15(P = 0.014) for surveillance,8.64(P = 0.039) for diagnostic and 3.34(P = 0.003) for surveillance and diagnostic combined.Although a multivariate Poisson regression suggested gender as a possibly significant factor,subset analysis showed that the difference between genders was not statistically significant.Age,bowel prep quality and withdrawal time did not significantly affect the RR of missing adenomas with SC vs TEC.Mean sizes of adenomas detected with TEC and SC were similar at 0.59 cm and 0.56 cm,respectively(P = NS).CONCLUSION:TEC allows detection of significantly more adenomas compared to SC in patients undergoing surveillance or diagnostic workup,but not in screening patients(ClinicalTrials.gov Identifier:NCT01044732).

Quality indicators for colonoscopy: Current insights and caveats

Colonoscopy is the diagnostic modality of choice for investigation of symptoms suspected to be related to the colon and for the detection of polyps and colorectal cancer(CRC). Colonoscopy with removal of detected polyps has been shown to reduce the incidence and mortality of subsequent CRC. In many countries, population screening programs for CRC have been initiated, either by selection of patients for colonoscopy with fecal occult blood testing or by offering colonoscopy directly to average-risk individuals. Several endoscopy societies have formulated quality indicators for colonoscopy. These quality indicators are almost always incorporated as process indicators, rather than outcome measures. This review focuses on the quality indicators bowel preparation, cecal intubation rate, withdrawal time, adenoma detection rate, patient comfort, sedation and complication rate, and discusses the scientific evidence supporting them,as well as their potential shortcomings and issues that need to be addressed. For instance, there is still no clear and generally accepted definition of adequatebowel preparation, no robust scientific evidence is available supporting a cecal intubation rate ≥ 90% and the association between withdrawal time and occurrence of interval cancers has not been clarified. Adenoma detection rate is currently the only quality indicator that has been shown to be associated with interval colorectal cancer, but as an indicator it does not differentiate between subjects with one or more adenoma detected.

Current understanding of the functional roles of aberrantly expressed micro RNAs in esophageal cancer

The incidence of esophageal cancer is rising,mostly because the increasing incidence of esophageal adenocarcino main Western countries.Despit eimprovements in diagnosis and treatment,the overall5-year survival rates remain low.Micro RNAs(mi RNAs)are small non-coding RNA molecules that regulate the expression of target genes.Recently,disease specific mi RNAs have been identified,which act as tumor suppressors or oncogenes.In this review,we will summarize the current knowledge about the function of aberrantly expressed mi RNAs in esophageal cancer.We selected 5 mi RNAs(mi RNA-21,-143,-145,-196a and let-7)based on the available literature,and described their potential role in regulating pathways that are deregulated in esophageal cancer.Finally we will highlight the current achievements of using and targeting mi RNAs.Because these mi RNAs likely have important regulatory roles in cancer development,they open a therapeutic window for new treatment modalities.

Endoscopic innovations to increase the adenoma detection rate during colonoscopy

Up to a quarter of polyps and adenomas are missed during colonoscopy due to poor visualization behind folds and the inner curves of flexures,and the presence of flat lesions that are difficult to detect.These numbers may however be conservative because they mainly come from back-to-back studies performed with standard colonoscopes,which are unable to visualize the entire mucosal surface.In the past several years,new endoscopic techniques have been introduced to improve the detection of polyps and adenomas.The introduction of high definition colonoscopes and visual image enhancement technologies have been suggested to lead to better recognition of flat and small lesions,but the absolute increase in diagnostic yield seems limited.Cap assisted colonoscopy and water-exchange colonoscopy are methods to facilitate cecal intubation and increase patients comfort,but show only a marginal or no benefit on polyp and adenoma detection.Retroflexion is routinely used in the rectum for the inspection of the dentate line,but withdrawal in retroflexion in the colon is in general not recommended due to the risk of perforation.In contrast,colonoscopy with the Third-Eye Retroscope?may result in considerable lower miss rates compared to standard colonoscopy,but this technique is not practical in case of polypectomy and is more time consuming.The recently introduced Full Spectrum Endoscopy?colonoscopes maintains the technical capabilities of standard colonoscopes and provides a much wider view of 330 degrees compared to the 170 degrees with standard colonoscopes.Remarkable lower adenoma miss rates with this new technique were recently demonstrated in the first randomized study.Nonetheless,more studies are required to determine the exact additional diagnostic yield in clinical practice.Optimizing the efficacy of colorectal cancer screening and surveillance requires high definition colonoscopes with improved virtual chromoendoscopy technology that visualize the whole colon mucosa while maintaining optimal washing,suction and therapeutic capabilities,and keeping the procedural time as low and patient discomfort as optimal as possible.

Adherence to surveillance guidelines for dysplasia and colorectal carcinoma in ulcerative and Crohn's colitis patients in the Netherlands

AIM: To study adherence to the widely accepted surveillance guidelines for patients with long-standing colitis in the Netherlands. METHODS: A questionnaire was sent to all 244 gastroenterologists in the Netherlands. RESULTS: The response rate was 63%. Of all gastroenterologists, 95% performed endoscopic surveillance in ulcerative colitis (UC) patients and 65% in patients with Crohn's colitis. The American Gastroenterological Association (AGA) guidelines were followed by 27%, while 27% and 46% followed their local hospital protocol or no specific protocol, respectively. The surveillance was correctly initiated in cases of pancolitis by 53%, and in cases of left-sided colitis by 44% of the gastroenterologists. Although guidelines recommend 4 biopsies every 10 cm, less than 30 biopsies per colonoscopy were taken by 73% of the responders. Only 31%, 68% and 58% of the gastroenterologists referred patients for colectomy when low-grade dysplasia, high-grade dysplasia (HGD) or Dysplasia Associated Lesion or Mass (DALM) was present, respectively. CONCLUSION: Most Dutch gastroenterologists performendoscopic surveillance without following international recommended guidelines. This practice potentially leads to a decreased sensitivity for dysplasia, rendering screening for colorectal cancer in this population highly ineffective.

Endoscopic ultrasound-guided ablation of solid pancreatic lesions:A systematic review of early outcomes with pooled analysis

BACKGROUND Endoscopic ultrasound-guided radiofrequency ablation(EUS-RFA)is emerging as a complementary therapeutic approach for pancreatic solid masses.However,results of published data are difficult to interpret because of a retrospective design and small sample size.AIM To systematically review data on EUS-RFA for solid lesions and to pool the results of the different experiences in order to provide more consistent evidence in terms of safety and efficacy.METHODS A comprehensive systematic literature search on the main databases was performed to identify articles in which patients with pancreatic solid lesions underwent EUS-RFA.The primary outcomes were procedure-related adverse events(AEs)and mortality.Secondary outcomes were the technical success rate and the effects on primary tumor growth.Statistical analyses were performed using Stata version 14.0.RESULTS In total,14 studies were included,with 120 patients undergoing 153 ablations of 129 solid pancreatic lesions.The STARmed technology was used in seven studies,the Habib system in six studies,and the HybridTherm probe in one study.The pooled technical success rate was 99.0%(I2:25.82%).The pooled overall AE rate was 8.0%(I2:11.46%).Excluding mild AEs,the pooled rates of serious AEs was 1.0%(I2:0%).No mortality related to the procedure was reported.CONCLUSION The present pooled analysis confirms the safety and feasibility of EUS-RFA.