Causes of intraprocedural discomfort in colonoscopy: a review and practical tips.

Colonoscopy is a commonly performed procedure in the United Kingdom and the gold standard for diagnosis and therapy in the gastrointestinal tract. Increased levels of pain during colonoscopy have been associated with reduced completion rates and difficulties in maintaining attendance for repeat procedures. Multiple factors play a role in causing discomfort intra-procedurally: patient factors, such as gender, anatomy and pre-procedure anxiety; operator factors, such as patient position and level of experience and other factors, such as bowel preparation and total procedure time.

Derivation and validation of a novel risk score to predict need for haemostatic intervention in acute upper gastrointestinal bleeding (London Haemostat Score).

Background: Acute upper gastrointestinal bleeding (AUGIB) is a common medical emergency, which takes up considerable healthcare resources. However, only approximately 20%-30% of bleeds require urgent haemostatic intervention. Current standard of care is for all patients admitted to hospital to undergo endoscopy within 24 hours for risk stratification, but this is difficult to achieve in practice, invasive and costly.

Does computer-aided diagnostic endoscopy improve the detection of commonly missed polyps? A meta-analysis.

Background/aims: Colonoscopy is the gold standard diagnostic method for colorectal neoplasia, allowing detection and resection of adenomatous polyps; however, significant proportions of adenomas are missed. Computer-aided detection (CADe) systems in endoscopy are currently available to help identify lesions. Diminutive (≤5 mm) and nonpedunculated polyps are most commonly missed.

The evolution of lower gastrointestinal endoscopy: where are we now?

Lower gastrointestinal endoscopy has evolved over time, fulfilling a widening diagnostic and therapeutic remit. As our understanding of colorectal cancer and its prevention has improved, endoscopy has progressed with improved diagnostic technologies and advancing endoscopic therapies. Despite this, the fundamental design of the endoscope has remained similar since its inception.

Endoscopic full thickness resection in the colo-rectum: outcomes from the UK Registry.

Background: Endoscopic full-thickness resection (eFTR) of the colon using the full-thickness resection device (FTRD) is a novel method for removing lesions involving, or tethered to, deeper layers of the colonic wall. The UK FTRD Registry collected data from multiple centres performing this procedure. We describe the technical feasibility, safety and early outcomes of this technique in the UK.

Endoscopic submucosal dissection: an update on tools and accessories.

Endoscopic submucosal dissection (ESD) is a minimally invasive therapeutic procedure to remove larger polyps or early non-metastatic lesions. It has long been used in Asia, but is now fast growing in popularity in the West. There are multiple challenges faced by ESD practitioners.

Discharge of patients with an acute upper gastrointestinal bleed from the emergency department using an extended Glasgow-Blatchford Score.

Objective: To use an extended Glasgow-Blatchford Score (GBS) cut-off of ≤1 to aid discharge of patients presenting with acute upper gastrointestinal bleeding (AUGIB) from emergency departments.

Background: The GBS accurately predicts the need for intervention and death in AUGIB, and a cut-off of 0 is recommended to identify patients for discharge without endoscopy. However, this cut-off is limited by identifying a low percentage of low-risk patients.

Derivation and validation of a novel risk score for safe discharge after acute lower gastrointestinal bleeding: a modelling study.

Background: Acute lower gastrointestinal bleeding is a common reason for emergency hospital admission, and identification of patients at low risk of harm, who are therefore suitable for outpatient investigation, is a clinical and research priority. We aimed to develop and externally validate a simple risk score to identify patients with lower gastrointestinal bleeding who could safely avoid hospital admission.

Methods: We undertook model development with data from the National Comparative Audit of Lower Gastrointestinal Bleeding from 143 hospitals in the UK in 2015.

Prediction of Outcome in Acute Lower Gastrointestinal Bleeding Using Gradient Boosting.

Background: There are no widely used models in clinical care to predict outcome in acute lower gastro-intestinal bleeding (ALGIB). If available these could help triage patients at presentation to appropriate levels of care/intervention and improve medical resource utilisation. We aimed to apply a state-of-the-art machine learning classifier, gradient boosting (GB), to predict outcome in ALGIB using non-endoscopic measurements as predictors.

Fluorescence lifetime spectroscopy of tissue autofluorescence in normal and diseased colon measured ex vivo using a fiber-optic probe.

We present an ex vivo study of temporally and spectrally resolved autofluorescence in a total of 47 endoscopic excision biopsy/resection specimens from colon, using pulsed excitation laser sources operating at wavelengths of 375 nm and 435 nm. A paired analysis of normal and neoplastic (adenomatous polyp) tissue specimens obtained from the same patient yielded a significant difference in the mean spectrally averaged autofluorescence lifetime -570 ± 740 ps (p = 0.021, n = 12).

Expansion of anti-mesothelin specific CD4+ and CD8+ T cell responses in patients with pancreatic carcinoma.

We aimed to assess the status of naturally occurring CD4(+) and CD8(+) T cell responses to a tumour associated antigen, Mesothelin, in patients with pancreatic carcinoma and study the effects of elevated IL-10 on Mesothelin-specific T cell responses. For that sake, short term T cell lines were generated from PBMCs of 16 healthy controls, 15 patients with benign pancreatic diseases and 25 patients with pancreatic carcinoma and Mesothelin-specific CD4(+) and CD8(+) T cell responses were analysed using intracellular cytokine assays for IFN-γ. Plasma levels of IL-10 and Mesothelin were measured using cytometric bead array and ELISA assay, respectively.

Length of Barrett's segment predicts success of extensive endomucosal resection for eradication of Barrett's esophagus with early neoplasia.

Background: Although the efficacy and safety of extensive endomucosal resection (EMR) in eradicating Barrett's esophagus (BE) harbouring early neoplasia have been established, factors predicting efficacy remains unclear.

Aim: To determine the complete eradication rate of Barrett's esophagus with high-grade intraepithelial neoplasia (HGIN) or intramucosal carcinoma (IMC), safety, and factors predicting complete eradication by EMR.

Methods: Patients with histological confirmation of Barrett's HGIN/IMC were prospectively identified.

Analysis of risk scoring for the outpatient management of acute upper gastrointestinal bleeding.

Objective: To determine whether the Glasgow-Blatchford bleeding score (GBS) or pre-endoscopy Rockall score was better at accurately identifying patients with acute upper gastrointestinal bleeding (AUGIB) who were at low risk of the need for clinical intervention and death and therefore suitable for outpatient management.

Design: Retrospective database and case note review of all patients admitted to the emergency departments with AUGIB from 1 January 2008 to 31 December 2009.

Setting: Two tertiary centre teaching hospitals.

R0 but not R1/R2 resection is associated with better survival than palliative photodynamic therapy in biliary tract cancer.

Background: There is a need for better management strategies to improve the survival and quality of life in patients with biliary tract cancer (BTC).

Aim: To assess prognostic factors for survival in a large, non-selective cohort of patients with BTC.

Method: We compared outcomes in 321 patients with a final diagnosis of BTC (cholangiocarcinoma n = 237, gallbladder cancer n = 84) seen in a tertiary referral cancer centre between 1998 and 2007.

The pharmacokinetics and safety of porfimer after repeated administration 30-45 days apart to patients undergoing photodynamic therapy.

Background: Porfimer is an intravenous (i.v.) injectable photosensitizing agent used in the photodynamic treatment of tumours and of high-grade dysplasia in Barrett's oesophagus.

Diagnosis of pancreaticobiliary malignancy by detection of minichromosome maintenance protein 5 in bile aspirates.

Biliary brush cytology is the standard method of sampling a biliary stricture but has a low sensitivity for the detection of malignancy. We have previously shown that minichromosome maintenance (MCM) replication proteins (Mcm2-7) are markers of dysplasia and have utilised these novel biomarkers of growth for the diagnosis of cervical and bladder cancer. We aimed to determine if MCM proteins are dysregulated in malignant pancreaticobiliary disease and if levels in bile are a sensitive marker of malignancy.

Human CD4(+) T cells recognize an epitope within alpha-fetoprotein sequence and develop into TGF-beta-producing CD4(+) T cells.

There is limited information on the influence of tumor growth on the expansion of tumor-specific TGF-beta-producing CD4(+) T cells in humans. alpha-Fetoprotein (AFP) is an oncofetal Ag and has intrinsic immunoregulatory properties. In this study, we report the identification and characterization of subsets of CD4(+) T cells that recognize an epitope within the AFP sequence (AFP(46-55)) and develop into TGF-beta-producing CD4(+) T cells.

Complications and diagnostic difficulties arising from biliary self-expanding metal stent insertion before definitive histological diagnosis.

Background: Self-expanding metal bile duct stents provide good palliation for inoperable malignant disease. However, problems may arise if metal stents are inserted before definitive histological diagnosis. The aim of this study was to evaluate the outcome of such patients.

Photodynamic therapy of malignant biliary strictures using meso-tetrahydroxyphenylchlorin.

Objectives: The palliation of patients with malignant bile duct obstruction using metal or plastic biliary stents may be limited by stent occlusion. The aim of this study was to determine the safety and efficacy of endoscopically delivered meso-tetrahydroxyphenyl chlorin photodynamic therapy in the treatment of irresectable malignant biliary strictures and recurrent stent occlusion.

Methods: Thirteen patients with malignant biliary obstruction owing to carcinoma of the biliary tract (n=9), pancreas (n=3) or stomach (n=1), were studied.

Photodynamic therapy using verteporfin photosensitization in the pancreas and surrounding tissues in the Syrian golden hamster.

Background/aim: Photodynamic therapy (PDT) is a potential treatment for locally advanced pancreatic cancer. We aimed to assess the safety of interstitial PDT using verteporfin (benzoporphyrin derivative monoacid A - a novel photosensitizer with a short drug-light interval and limited cutaneous photosensitivity) in the Syrian golden hamster, and compare it to meso-tetrahydroxyphenylchlorin (mTHPC) which we have previously evaluated in preclinical and clinical studies.

Methods: Verteporfin (2 mg/kg) was administered at laparotomy by inferior vena caval injection (n = 57), with plasma levels quantified at 5, 15, 30, 60 and 240 min, and 24 h.

Unmasking of alpha-fetoprotein-specific CD4(+) T cell responses in hepatocellular carcinoma patients undergoing embolization.

Necrosis of tumor cells can activate both innate and adaptive antitumor immunity. However, there is little information on the effects of necrosis-inducing cancer treatments on tumor-specific T cell immune responses in humans. We studied the effects of a necrosis-inducing treatment (embolization) on anti-alpha-fetoprotein (AFP)-specific CD4(+) T cell responses in hepatocellular carcinoma (HCC) patients and controls using an array of AFP-derived peptides.

Photodynamic therapy for pancreatic and biliary tract carcinoma.

The prognosis of patients with pancreatic and biliary tract cancer treated with conventional therapies such as stent insertion or chemotherapy is often poor, and new approaches are urgently needed. Surgery is the only curative treatment but is appropriate in less than 20% of cases, and even then it is associated with a 5-yr survival of less than 30% in selected series. Photodynamic therapy represents a novel treatment for pancreaticobiliary malignancy.

Photodynamic therapy for pancreatic carcinoma: experimental and clinical studies.

Pancreatic carcinoma is the sixth leading cause of cancer-related mortality in the United Kingdom, with an overall 5-year survival of less than 5%. Attempted curative surgery is possible in less than 20% of cases and is associated with a 5-year survival of just 10-20%. Palliative radio-chemotherapy improves symptoms of pancreatic cancer but rarely extends median survival beyond 12 months.