Sorafenib in the treatment of hepatocellular carcinoma: a multi-centre real-world study.

OBJECTIVE: Sorafenib is an oral multikinase inhibitor that improves survival in advanced hepatocellular carcinoma (HCC). In the absence of alternative therapies, sorafenib is often continued despite advancing liver disease or tumour progression. Real world studies are important to better characterise outcomes in these populations. Our aim was to review patterns of sorafenib use across eight Australian tertiary hospitals, defining variables associated with clinical outcomes. MATERIAL AND METHODS: Retrospective cohort study of medical records of 320 patients treated with sorafenib for HCC. Baseline clinical parameters, dosage, adverse effects, and survival from initiation of treatment were collected. Time to radiological progression and 3-month alpha-fetoprotein (AFP) levels were available for a subset of patients. RESULTS: Adverse effects occurred in 79% of patients, requiring dose reduction in 31% of patients. Multivariate analysis identified an increased rate of mortality with Child-Pugh C (HR 5.52, p = 0.012), ECOG performance status 2-3 (HR 2.84, p = 0.001), and extrahepatic metastases (HR 1.54, p = 0.04), and decreased rate of mortality with an AFP reduction of at least 20% at 3 months (HR 0.38, p = 0.001). An increased rate of radiological progression was associated with ECOG performance status 2-3 (HR 2.34, p = 0.041), whilst a decreased rate of radiological progression was associated with development of on-treatment diarrhoea (HR 0.55, p = 0.015). CONCLUSIONS: Survival in patients with Child-Pugh C liver function or advanced functional impairment treated with sorafenib is poor and thus routine use of this agent in these patients does not appear justified, particularly given the high rate of adverse effects. AFP concentration on therapy may help identify favourable response to treatment.

A prospective dual-center proof-of-principle study evaluating the incremental benefit of narrow-band imaging with a fixed zoom function in real-time prediction of polyp histology. Can we resect and discard?

BACKGROUND: Advancements in endoscopic technology have increased the ability to distinguish neoplastic polyps during colonoscopy. If a minimum accuracy can be achieved, then a resect-and-discard model can be implemented, although studies to date have demonstrated limited success, especially in the assessment of serrated polyps. OBJECTIVE: To perform a proof-of-principle study assessing the accuracy of narrow-band imaging with near focus in predicting polyp histology including serrated polyps and to determine whether the minimum requirements can be achieved for a resect-and-discard policy. DESIGN: Dual-center, prospective case series. SETTING: Two tertiary-care referral endoscopic centers in Australia. PATIENTS: Two hundred consecutive patients undergoing colonoscopy for routine indications were recruited. INTERVENTIONS: Any polyps identified were assessed by using standard white light followed by narrow-band imaging with near focus for Kudo pit patterns and modified Sano capillary patterns. Based on this assessment and the macroscopic appearance, the polyp histology was predicted and subsequently compared with histopathology results. MAIN OUTCOME MEASUREMENTS: Correlation in postpolypectomy surveillance intervals between endoscopic and pathologic assessments as well as negative predictive value for rectosigmoid hyperplastic polyps. RESULTS: There was a 96% agreement for surveillance intervals between endoscopic assessment and histology by using the American Society for Gastrointestinal Endoscopy guidelines. There was a 96% negative predictive value in assessing rectosigmoid hyperplastic polyps. LIMITATIONS: Because this was a proof-of-principle study, there was no control arm, and there were small numbers, especially in assessing subgroups. The results have limited generalizability with the training requirements for polyp recognition, with confidence to be determined. CONCLUSION: Narrow-band imaging with near focus can predict polyp histology (including serrated polyps) accurately in the hands of trained endoscopists. Further studies with larger numbers are required to further validate this practice.

Persistence of Human Papillomavirus, Overexpression of p53, and Outcomes of Patients After Endoscopic Ablation of Barrett's Esophagus.

We investigated the role of high-risk human papillomavirus (hr-HPV) in patients with Barrett's dysplasia and adenocarcinoma (EAC). Clearance vs persistence of HPV (DNA, E6 or E7 mRNA, and p16INK4A protein) and overexpression or mutation of p53 were determined for 40 patients who underwent endotherapy for Barrett's dysplasia or EAC. After ablation, dysplasia or neoplasia was eradicated in 34 subjects (24 squamous, 10 intestinal metaplasia). Six patients had detectable lesions after treatment; 2 were positive for transcriptionally active hr-HPV, and 4 had overexpression of p53. Before endotherapy, 15 patients had biologically active hr-HPV, 13 cleared the infection with treatment, and dysplasia or EAC was eliminated from 12 patients. One patient who cleared HPV after ablation acquired a p53 mutation, and their cancer progressed. Of 13 patients with overexpression of p53 before treatment, 10 cleared the p53 abnormality after ablation with eradication of dysplasia or neoplasia, whereas 3 of 13 had persistent p53 mutation-associated dysplasia after endotherapy (P = .004). Immunohistochemical and sequence analyses of p53 produced concordant results for 36 of 40 samples (90%). Detection of dysplasia or neoplasia after treatment was associated with HPV persistence or continued p53 overexpression.

Small bowel stricture characterization and outcomes of dilatation by double-balloon enteroscopy: a single-centre experience.

BACKGROUND: There is little data on the role of balloon enteroscopy and small bowel strictures. We aim to characterize the diagnostic role of double balloon enteroscopy (DBE) in small bowel strictures and document the outcomes of dilatation. METHODS: This is a retrospective review from a single tertiary referral centre DBE database from July 2004 to September 2012. All patients with suspected strictures in the small bowel undergoing DBE were included. The position of the small bowel strictures considered for dilatation was determined by diagnostic imaging, i.e. CT enterography, MR enterography or capsule endoscopy in the workup before DBE. Endpoints included stricture description, dilatation parameters and response to treatment. Main outcome measurements were the safety and efficacy of DBE and dilatation. RESULTS: From our DBE database of 594 patients, a total of 32 patients underwent 44 DBE procedures for suspected or known strictures. Stricture aetiology included Crohn's disease (CD), nonsteroidal anti-inflammatory drugs (NSAIDs), surgical, Beçhets disease and one unknown. A total of 17 patients did not undergo dilatation as the strictures were ulcerated, nonobstructing or of uncertain aetiology. From the total of 25 dilatations in 15 patients that were attempted, 8/15 (53%) patients had 1 dilatation, 5 patients had 2 dilatations, 1 had 3 dilatations and 1 had 4 dilatations. The mean dilatation diameter was 14 mm. Three patients underwent surgery post-dilatation (2 for perforation). Mean follow up was 16 months. CONCLUSION: DBE is a useful method in determining the need for dilatation by assessing for active ulceration. Dilatation is effective in the 10-18 mm range, however perforation does occur.

A randomized trial of a fully covered self-expandable metallic stent versus plastic stents in anastomotic biliary strictures after liver transplantation.

BACKGROUND: Post-liver-transplant biliary anastomotic strictures (ASs) are currently managed with repeated endoscopic retrograde cholangiopancreatographies (ERCPs) inserting multiple plastic stents. Fully covered self-expanding metal stents (FCSEMSs) are being increasingly reported in the management of this condition, however no prospective randomized trials have been performed to date. AIM: The aim of this study was to determine whether FCSEMSs decrease overall numbers of ERCPs needed to achieve stricture resolution and to establish the safety, efficacy and cost-effectiveness in this setting. METHODS: Two tertiary referral centres performed this open-label prospective randomized trial. A total of 32 patients consented and subsequently 20 were randomized with 10 in the FCSEMS arm and 10 in the plastic arm. The FCSEMS arm had the stent in situ for 12 weeks with the plastic stent arm undergoing 3-monthly multiple plastic stenting with or without dilatation over a year. RESULTS: The median number of ERCPs performed per patient in the FCSEMS was 2 versus 4.5 (p = 0.0001) in the plastic stenting arm. Stricture resolution was achieved in all 10 patients with FCSEMSs compared with 8/10 in the plastic arm [p = not significant (NS)]. Complications occurred in 1/10 patients in the FCSEMS arm versus 5/10 in the plastic arm (p = 0.051). Days in hospital for complications was 6 in the FCSEMS versus 56 in the plastic arm (p = 0.11). Cost analysis shows that the FCSEMS arm was more cost effective. No cases of FCSEMS migration were seen. CONCLUSIONS: FCSEMSs reduced the number of ERCPs needed to achieve stricture resolution with similar recurrence rates between arms. The FCSEMSs may do so with fewer complications making it cost effective.

Management of noncardiac chest pain in women.

Noncardiac chest pain (NCCP) is very prevalent in the community. Although mortality remains low, morbidity and the financial implications are high. Women, especially those of middle age, should be thoroughly investigated as per current guidelines for coronary artery disease before labeling their chest pain as NCCP. Gastroesophageal reflux disease is the most common cause of NCCP; however other esophageal pathology including esophageal hypersensitivity, neuromuscular disease and eosinophilic esophagitis may also cause NCCP. Proton pump inhibitors are commonly used initially to manage NCCP, although patients who do not respond to this therapy require further investigation and differing treatment regimes. This article will focus on current knowledge regarding GI tract-related NCCP management strategies.

Endoscopic imaging in Barrett's esophagus: current practice and future applications.

Barrett's esophagus (BE) is a condition that develops as a consequence of chronic gastroesophageal reflux disease in which stratified squamous epithelium is replaced by metaplastic columnar epithelium which in turn predisposes to the development of adenocarcinoma of esophagus. In this review article, we discuss recent advances in the endoscopic imaging techniques for the detection of dysplasia and early carcinoma in BE. This will include some of the current available novel technologies as well as future applications specifically concentrating on high-resolution endoscopy, narrow band imaging, chromoendoscopy, confocal laser endomicroscopy and autofluorescence imaging.