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1.
Br J Radiol ; 91(1091): 20170935, 2018 Nov.
Article in English | MEDLINE | ID: mdl-29888981

ABSTRACT

Oesophageal stents are widely used for palliating dysphagia from malignant obstruction. They are also used with increasing frequency in the treatment of oesophageal perforation, as well as benign strictures from a variety of causes. Improved oncological treatments have led to prolonged survival of patients treated with palliative intent; as a consequence, stents need to function and last longer in order to avoid repeat procedures. There is also increasing need for meticulous procedure planning, careful selection of the device most appropriate for the individual patient and planned follow-up. Furthermore, as more patients are cured, there will be more issues with resultant long-term side-effects, such as recalcitrant strictures due to radiotherapy or anastomotic scarring, which will have to be addressed. Stent design needs to keep up with the progress of cancer treatment, in order to offer patients the best possible long-term result. This review article attempts to illustrate the changing realities in oesophageal stenting, differences in current stent designs and behaviour, as well as the pressing need to refine and modify devices in order to meet the new challenges.


Subject(s)
Esophageal Diseases/therapy , Stents/trends , Absorbable Implants/trends , Airway Obstruction/etiology , Device Removal/trends , Esophageal Fistula/etiology , Foreign-Body Migration/prevention & control , Humans , Prosthesis Design/trends , Recurrence , Stents/adverse effects
2.
Oncotarget ; 7(19): 28556-69, 2016 May 10.
Article in English | MEDLINE | ID: mdl-27086919

ABSTRACT

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease. Novel biomarkers are required to aid treatment decisions and improve patient outcomes. MicroRNAs (miRNAs) are potentially ideal diagnostic biomarkers, as they are stable molecules, and tumour and tissue specific. RESULTS: Logistic regression analysis revealed an endoscopic-ultrasound fine-needle aspiration (EUS-FNA) 2-miRNA classifier (miR-21 + miR-155) capable of distinguishing benign from malignant pancreatic lesions with a sensitivity of 81.5% and a specificity of 85.7% (AUC 0.930). Validation FNA cohorts confirmed both miRNAs were overexpressed in malignant disease, while circulating miRNAs performed poorly. METHODS: Fifty-five patients with a suspicious pancreatic lesion on cross-sectional imaging were evaluated by EUS-FNA. At echo-endoscopy, the first part of the FNA was sent for cytological assessment and the second part was used for total RNA extraction. Candidate miRNAs were selected after careful review of the literature and expression was quantified by qRT-PCR. Validation was performed on an independent cohort of EUS-FNAs, as well as formalin-fixed paraffin embedded (FFPE) and plasma samples. CONCLUSIONS: We provide further evidence for using miRNAs as diagnostic biomarkers for pancreatic malignancy. We demonstrate the feasibility of using fresh EUS-FNAs to establish miRNA-based signatures unique to pancreatic malignant transformation and the potential to enhance risk stratification and selection for surgery.


Subject(s)
Cell Transformation, Neoplastic/genetics , Endoscopic Ultrasound-Guided Fine Needle Aspiration/methods , Gene Expression Regulation, Neoplastic , MicroRNAs/genetics , Pancreas/metabolism , Pancreatic Neoplasms/genetics , Adult , Aged , Female , Gene Expression Profiling/methods , Humans , Logistic Models , Male , Middle Aged , Pancreas/pathology , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/pathology , Prospective Studies , Sensitivity and Specificity
3.
Dig Dis Sci ; 60(11): 3449-55, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26038094

ABSTRACT

BACKGROUND: Pancreatic carcinoma is often inoperable, carries a poor prognosis, and is commonly complicated by malignant biliary obstruction. Phase I/II studies have demonstrated good safety and early stent patency using endoscopic biliary radiofrequency ablation (RFA) as an adjunct to self-expanding metal stent (SEMS) insertion for biliary decompression. AIM: To analyze the clinical efficacy of endobiliary RFA. METHODS: Retrospective case-control analysis was carried out for 23 patients with surgically unresectable pancreatic carcinoma and malignant biliary obstruction undergoing endoscopic RFA and SEMS insertion and 46 controls (SEMS insertion alone) in a single tertiary care center. Controls were stringently matched for age, sex, metastases, ASA/comorbidities. Survival, morbidity, and stent patency rates were assessed. RESULTS: RFA and control groups were closely matched-ASA 2.35 ± 0.65 versus 2.54 ± 0.50, p = 0.086; metastases 9/23 (39.1%) versus 18/46 (39.1%), p = 0.800; chemotherapy 16/23 (69.6%) versus 24/46 (52.2%), p = 0.203. Median survival in RFA group was 226 days (IQR 140-526 days) versus 123.5 days (IQR 44-328 days) in controls (p = 0.010). RFA was independently predictive of survival at 90 days (OR 21.07, 95% CI 1.45-306.64, p = 0.026) and 180 days (OR 4.48, 95% CI 1.04-19.30, p = 0.044) in multivariate analysis. SEMS patency rates were equivalent in both groups. RFA was well tolerated with minimal side effects. CONCLUSIONS: Endoscopic RFA is a safe and efficacious adjunctive treatment in patients with advanced pancreatic malignancy and biliary obstruction and may confer early survival benefit. Randomized prospective clinical trials of this new modality are mandated.


Subject(s)
Catheter Ablation , Cholangiopancreatography, Endoscopic Retrograde , Cholestasis/surgery , Pancreatic Neoplasms/complications , Aged , Aged, 80 and over , Catheter Ablation/adverse effects , Catheter Ablation/mortality , Chi-Square Distribution , Cholangiopancreatography, Endoscopic Retrograde/adverse effects , Cholangiopancreatography, Endoscopic Retrograde/instrumentation , Cholangiopancreatography, Endoscopic Retrograde/mortality , Cholestasis/diagnosis , Cholestasis/etiology , Cholestasis/mortality , Drainage/instrumentation , Female , Humans , Kaplan-Meier Estimate , London , Male , Middle Aged , Multivariate Analysis , Odds Ratio , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/mortality , Retrospective Studies , Risk Factors , Stents , Tertiary Care Centers , Time Factors , Treatment Outcome
4.
Scand J Gastroenterol ; 49(10): 1237-44, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25007715

ABSTRACT

OBJECTIVE: To evaluate the diagnostic utility of single-operator peroral cholangioscopy (SOC) in patients with sclerosing cholangitis. METHODS: All patients with sclerosing cholangitis who underwent SOC procedures due to suspicious biliary strictures, in one Swedish and four UK tertiary centers in 2008-2012, were retrospectively enrolled. For each SOC procedure in sclerosing cholangitis, another one attempted due to a single biliary stricture in the same center and calendar year was randomly selected as control. Patients were followed up until death or last clinic visit until November 2012. RESULTS: Fifty-four SOC procedures were attempted in 52 sclerosing cholangitis patients (48 with primary sclerosing cholangitis, 4 with IgG4-related sclerosing cholangitis). Cannulation with the SOC system failed more frequently in sclerosing cholangitis (15% vs. 2% in controls; p = 0.015). The sensitivity, specificity, and accuracy of SOC (including tissue sampling) for cancer diagnosis were similar in sclerosing cholangitis and controls (50% vs. 55%, 100% vs. 97%, and 88% vs. 80%, respectively) with largely overlapping confidence intervals. Adverse events were more common in sclerosing cholangitis, due to an increased frequency of cholangitis (11% vs. 2% in controls; p = 0.051). CONCLUSIONS: SOC is equally accurate in cancer diagnosis in sclerosing cholangitis and patients with single biliary strictures. However, cholangioscope insertion may be hampered by bile duct narrowing and post-SOC cholangitis is more common in sclerosing cholangitis.


Subject(s)
Bile Duct Neoplasms/diagnosis , Cholangitis, Sclerosing/diagnosis , Endoscopy, Digestive System/methods , Adult , Aged , Bile Duct Neoplasms/complications , Bile Duct Neoplasms/pathology , Bile Ducts , Biopsy , Case-Control Studies , Catheterization , Cholangitis, Sclerosing/complications , Cholangitis, Sclerosing/pathology , Constriction, Pathologic/etiology , Endoscopy, Digestive System/adverse effects , False Positive Reactions , Female , Humans , Male , Middle Aged , Mouth , Predictive Value of Tests , Retrospective Studies
5.
J Immunol Methods ; 370(1-2): 43-54, 2011 Jul 29.
Article in English | MEDLINE | ID: mdl-21669205

ABSTRACT

The next generation of candidate HIV vaccines include replicating vectors selected for tropism to mucosal sites, where an efficacious T cell response will be required to limit T cell replication and HIV associated CD4 T cell loss. To fully assess immunogenicity of such candidates, there is a need to develop robust quality controlled analysis of gut derived HIV specific CD8+ T-cell responses. Despite obvious challenges in obtaining sufficient amounts of tissue, the highly compartmentalised nature of the mucosal immune responses, requires the assessment of CD8 T cells isolated directly from local tissue before any conclusions regarding the induction of mucosal responses are made. Here we describe the optimisation and subsequent qualification of a qualitative and quantitative polychromatic flow cytometry assay to assess antigen specific CD8+ T cells isolated from the gut, using samples from HIV positive and negative volunteers. Internal quality controls monitored over time, combined with the use of quality gating and standard operating procedures were used to demonstrate the generation of robust and reliable data.


Subject(s)
AIDS Vaccines/immunology , Cell Separation/methods , Flow Cytometry/methods , Intestinal Mucosa/immunology , T-Lymphocytes/immunology , Adult , Aged , Biopsy , Female , Humans , Male , Middle Aged , Young Adult
6.
J Infect Dis ; 201(5): 720-9, 2010 Mar.
Article in English | MEDLINE | ID: mdl-20132004

ABSTRACT

We have characterized an assay measuring CD8 T cell-mediated inhibition of human immunodeficiency virus (HIV) type 1 replication, demonstrating specificity and reproducibility and employing a panel of primary HIV-1 isolates. The assay uses relatively simple autologous cell culture and enzyme-linked immunosorbent assay, avoids generation of T cell clones, and can be performed with <2 million peripheral blood mononuclear cells. Efficient CD8 T cell-mediated cross-clade inhibition of HIV-1 replication in vitro was demonstrated in antiretroviral therapy-naive HIV-1-infected subjects with controlled viral replication in vivo but not in viremic subjects. An HIV-1 vaccine candidate, consisting of DNA and recombinant adenovirus 5 vectors tested in a phase I clinical trial, induced CD8 T cells that efficiently inhibited HIV-1 in a HLA-I-dependent manner. Assessment of direct antiviral T cell function by this assay provides additional information to guide vaccine design and the prioritizing of candidates for further clinical trials.


Subject(s)
AIDS Vaccines/immunology , CD8-Positive T-Lymphocytes/immunology , HIV-1/immunology , Neutralization Tests/methods , AIDS Vaccines/genetics , Adenoviruses, Human/genetics , Adult , Aged , Cells, Cultured , Enzyme-Linked Immunosorbent Assay/methods , Female , Genetic Vectors , Humans , Male , Middle Aged , Reproducibility of Results , Sensitivity and Specificity , Virus Replication/immunology
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