Multi-organ assessment of compensated cirrhosis patients using quantitative magnetic resonance imaging.

BACKGROUND & AIMS: Advancing liver disease results in deleterious changes in a number of critical organs. The ability to measure structure, blood flow and tissue perfusion within multiple organs in a single scan has implications for determining the balance of benefit vs. harm for therapies. Our aim was to establish the feasibility of magnetic resonance imaging (MRI) to assess changes in Compensated Cirrhosis (CC), and relate this to disease severity and future liver-related outcomes (LROs). METHODS: A total of 60 patients with CC, 40 healthy volunteers and 7 patients with decompensated cirrhosis were recruited. In a single scan session, MRI measures comprised phase-contrast MRI vessel blood flow, arterial spin labelling tissue perfusion, T1 longitudinal relaxation time, heart rate, cardiac index, and volume assessment of the liver, spleen and kidneys. We explored the association between MRI parameters and disease severity, analysing differences in baseline MRI parameters in the 11 (18%) patients with CC who experienced future LROs. RESULTS: In the liver, compositional changes were reflected by increased T1 in progressive disease (p <0.001) and an increase in liver volume in CC (p = 0.006), with associated progressive reduction in liver (p <0.001) and splenic (p <0.001) perfusion. A significant reduction in renal cortex T1 and increase in cardiac index and superior mesenteric arterial blood flow was seen with increasing disease severity. Baseline liver T1 (p = 0.01), liver perfusion (p <0.01), and renal cortex T1 (p <0.01) were significantly different in patients with CC who subsequently developed negative LROs. CONCLUSIONS: MRI enables the contemporaneous assessment of organs in liver cirrhosis in a single scan without the requirement for a contrast agent. MRI parameters of liver T1, renal T1, hepatic and splenic perfusion, and superior mesenteric arterial blood flow were related to the risk of LROs. LAY SUMMARY: This study assesses the changes to structure, blood flow and perfusion that occur in the key organs (liver, spleen and kidney) associated with severe liver disease (Compensated Cirrhosis), using magnetic resonance imaging. The magnetic resonance imaging measures which changed with disease severity and were related to negative liver-related clinical outcomes are described.

Quality standards in upper gastrointestinal endoscopy: a position statement of the British Society of Gastroenterology (BSG) and Association of Upper Gastrointestinal Surgeons of Great Britain and Ireland (AUGIS).

This document represents the first position statement produced by the British Society of Gastroenterology and Association of Upper Gastrointestinal Surgeons of Great Britain and Ireland, setting out the minimum expected standards in diagnostic upper gastrointestinal endoscopy. The need for this statement has arisen from the recognition that while technical competence can be rapidly acquired, in practice the performance of a high-quality examination is variable, with an unacceptably high rate of failure to diagnose cancer at endoscopy. The importance of detecting early neoplasia has taken on greater significance in this era of minimally invasive, organ-preserving endoscopic therapy. In this position statement we describe 38 recommendations to improve diagnostic endoscopy quality. Our goal is to emphasise practices that encourage mucosal inspection and lesion recognition, with the aim of optimising the early diagnosis of upper gastrointestinal disease and improving patient outcomes.

A role for the vacuolating cytotoxin, VacA, in colonization and Helicobacter pylori-induced metaplasia in the stomach.

Carriage of Helicobacter pylori strains producing more active (s1/i1) forms of VacA is strongly associated with gastric adenocarcinoma. To our knowledge, we are the first to determine effects of different polymorphic forms of VacA on inflammation and metaplasia in the mouse stomach. Bacteria producing the less active s2/i2 form of VacA colonized mice more efficiently than mutants null for VacA or producing more active forms of it, providing the first evidence of a positive role for the minimally active s2/i2 toxin. Strains producing more active toxin forms induced more severe and extensive metaplasia and inflammation in the mouse stomach than strains producing weakly active (s2/i2) toxin. We also examined the association in humans, controlling for cagPAI status. In human gastric biopsy specimens, the vacA i1 allele was strongly associated with precancerous intestinal metaplasia, with almost complete absence of intestinal metaplasia in subjects infected with i2-type strains, even in a vacA s1, cagA(+) background.

Mixed periampullary adenocarcinoma and somatostatinoma with small bowel gastrointestinal stromal tumour in neurofibromatosis type 1.

CONTEXT: Gastrointestinal (GI) involvement is present in about one quarter of cases of neurofibromatosis type 1 (NF1). Adenocarcinomas have been reported in several organs. Gastrointestinal stromal tumors are the most common GI lesion seen in NFI. GISTs in combination with ampullary neuroendocrine tumors in NF-1 have been reported rarely. CASE REPORT: We present the case of a 44-year-old man who presented with a history of obstructive jaundice and weight loss. Investigations revealed a pancreatic tumor associated with a common bile duct (CBD) stricture. At operation, an ampullary adenocarcinoma that infiltrated into the head of pancreas with an adjacent somatostatinoma was found. In addition, a small bowel GIST was present. CONCLUSIONS: Mixed periampullary adenocarcinoma and somatostatinoma in a patient with NF1 has only been previously reported once. The current case highlights the spectrum of associated tumor types which can be seen in association with NF1. Patients with NF1 who present with jaundice and weight loss should be investigated in the usual manner with increased suspicion for duodenal and ampullary tumors.

Lymphoepithelial cyst of the pancreas and elevated cyst fluid carcinoembryonic antigen: a diagnostic challenge.

CONTEXT: Pancreatic lymphoepithelial cysts are rare, benign cysts which can present diagnostic difficulties. Non-invasive imaging alone is unreliable in distinguishing between benign and malignant cysts. Endoscopic ultrasound (EUS) and fine needle aspiration (FNA) with analysis of cyst fluid is more reliable, but invasive. In addition, tumor markers such as carcinoembryonic antigen (CEA) can be grossly elevated in cyst fluid of benign cysts. CASE REPORT: We present the case of a 67 year old man with an incidental finding of a pancreatic cyst. EUS and FNA-guided aspiration of cyst fluid was performed. Fluid CEA was grossly elevated and resectional surgery was performed. On histological examination the diagnosis was confirmed as lymphoepithelial cyst of the pancreas. CONCLUSION: Tumor markers such as CEA can be elevated in the cyst fluid of benign pancreatic conditions such as lymphoepithelial cyst. Although the diagnosis is challenging preoperatively, if a systematic algorithm is followed, these conditions can be managed safely and efficiently.

Endoscopic management of Barrett's dysplasia and early neoplasia: efficacy, safety and long-term outcomes in a UK tertiary centre.

BACKGROUND AND OBJECTIVES: Endoscopic mucosal resection (EMR) and radiofrequency ablation (RFA) are effective treatments for dysplastic Barrett's esophagus (BE). This study evaluates efficacy, durability and safety in a single high-volume UK tertiary centre with 15-years' experience. METHODS: Prospective data were collected from Nottingham University Hospitals 2004-2019 for endotherapy of dysplastic BE or intramucosal adenocarcinoma. Procedural outcome measures include complete resection, complications and surgery rates. Efficacy outcomes include complete remission of dysplasia (CR-D) and intestinal metaplasia (CR-IM), recurrence, treatment failure rates, durability of RFA, median follow up and tumor-associated mortality. RESULTS: A total of 319 lesions were resected; 671 RFAs were performed on 239 patients. Median age was 67 (±9.5) years, male:female ratio was 5:1 and median BE length was C3 [interquartile range (IQR): 6] M6 (IQR: 5). The most common lesion was Paris IIa (64%) with a median size of 10 mm (3-70). Final histology was adenocarcinoma in 50%. Complete resection rates were 96%. The multiband mucosectomy technique (91%) was most commonly used. The median number of RFA sessions was 3 (IQR: 2). The rates of CR-D and CR-IM were 90.4%% and 89.8% achieved after a median of 20.1 (IQR: 14) months. The most common complications: EMR was bleeding 2.2% and RFA was stricture (5.4%) requiring a median of 2 (range 1-7) dilatations. Median follow up post CR-IM/CR-D was 38 months (14-60). Metachronous lesions developed in 4.7% after CR-D and tumor-related mortality was 0.8%. Dysplasia and intestinal metaplasia-free survival at 5 years was 95 and 90%, respectively. CONCLUSION: BE endotherapy is minimally invasive, effective, safe and deliverable in a day-case setting.

EUS-guided pancreatic cyst brushing: a comparative study in a tertiary referral centre.

CONTEXT: Fluid analysis obtained by EUS guided FNA is used to aid in diagnosis and management of cystic lesions in the pancreas. Complementing fluid aspiration with brushing of cyst wall may increase the cellular yield. OBJECTIVE: To compare cellular yield of pancreatic cyst FNA with and without wall brushing. DESIGN: Comparative study. SETTING: Tertiary referral centre. PATIENTS: Fifty-one patients with cystic pancreatic lesions referred for EUS-guided aspiration/sampling were included (median age 69 years; interquartile range: 49-77 years). MAIN OUTCOME MEASURES: Comparing adequacy of cellular yield between EUS-guided aspiration alone vs. EUS-guided aspiration and cyst wall brushing. INTERVENTION: EUS-guided FNA and/or wall brushing (aspiration only: No. 27; brushing: No. 24). RESULTS: There was no significant difference in age (P=0.496) cyst size (P=0.084) or cyst location (P=0.227) between groups. Overall 29.5%; (15/51) of samples were acellular/insufficient with no significant difference between the two groups (22.2% in the aspiration only group vs. 37.5% in the brushing group; P=0.356). The remaining samples were adequate for cytological evaluation (77.8% vs. 62.5%; aspiration only vs. brushing groups). Seventeen cases were neoplastic (8 benign, 9 malignant). The diagnostic accuracy was 61.9% and 55.0% in aspiration only and brushing groups, respectively. Two out of 4 (50.0%) patents were diagnosed as having cancer in the brushings group compared to 1/5 (20.0%) in the FNA only group (P=0.524). LIMITATIONS: Non-randomised series. CONCLUSIONS: The cellular yield was similar in FNA and brushing group. Greater proportion of patients with malignant cystic pancreatic lesions diagnosed by EUS sampling was in the brushing group, but this did not reach statistical significance.

Efficacy, safety, and predictive factors for a positive yield of EUS-guided Trucut biopsy: a large tertiary referral center experience.

OBJECTIVES: Endoscopic ultrasound-guided trucut biopsy (EUS-TCB) technique has the advantage of obtaining tissue for histological examination rather than for cytology alone. However, the diagnostic yield may depend on factors related to both technical aspects and the lesions sampled. Safety of EUS-TCB is yet to be established in a large number of procedures. The aim of the study was to determine factors predicting a positive diagnostic yield, and safety for EUS-TCB in a large tertiary referral center-based service. METHODS: All patients were referred for EUS-guided tissue sampling as a part of their diagnostic workup. Linear-array echoendoscope (GF-2000-OL5, KeyMed) with a 19-gauge trucut needle (Quick-Core, Wilson-Cook) was used by two operators to obtain tissue samples. Clinical data, details of the EUS-TCB, post-procedure complications, and histology were prospectively collected between May 2002 and February 2008. RESULTS: In total, 247 patients (143 men) aged 57-73 (median 66) had EUS-TCB performed. Lesions sampled were in the pancreas (113), esophagogastric wall (34), and extra-pancreatic areas (100) (lymph nodes: 52). The maximum diameter of the lesion/wall thickness ranged from 0.6 to 5.4 cm (median 3). One to five passes were made (median 3) to obtain tissue cores 2-18 mm (median 10) in length. The procedure failed in 6% of cases. The overall diagnostic accuracy was 75%. The overall complication rate was 2% (bronchopneumonia, minor hemoptysis, minor hematemesis, mucosal tear, retropharyngeal abscess) with no procedure-related deaths. Site of lesion (pancreatic vs. extra-pancreatic, P<0.032), site of biopsy (stomach vs. duodenum vs. esophagus, P<0.001), and number of passes (< or =2 vs.>2, P<0.013) were predictors of a positive diagnostic yield in univariate analysis. However, only the site of biopsy (P<0.001, 95% CI: 0.58-2.32) and number of passes (P=0.05) were independent predictors in multinominal logistic regression. CONCLUSIONS: Diagnostic yield of EUS-TCB is higher when lesion is approached through the stomach and better when more than two passes were made. In this large series, the complication rate of 2% associated with EUS-TCB was similar to that reported with EUS-fine needle aspiration technique.

Risk stratification of Barrett's oesophagus using a non-endoscopic sampling method coupled with a biomarker panel: a cohort study.

BACKGROUND: Barrett's oesophagus predisposes to adenocarcinoma. However, most patients with Barrett's oesophagus will not progress and endoscopic surveillance is invasive, expensive, and fraught by issues of sampling bias and the subjective assessment of dysplasia. We investigated whether a non-endoscopic device, the Cytosponge, could be coupled with clinical and molecular biomarkers to identify a group of patients with low risk of progression suitable for non-endoscopic follow-up. METHODS: In this multicentre cohort study (BEST2), patients with Barrett's oesophagus underwent the Cytosponge test before their surveillance endoscopy. We collected clinical and demographic data and tested Cytosponge samples for a molecular biomarker panel including three protein biomarkers (P53, c-Myc, and Aurora kinase A), two methylation markers (MYOD1 and RUNX3), glandular atypia, and TP53 mutation status. We used a multivariable logistic regression model to compute the conditional probability of dysplasia status. We selected a simple model with high classification accuracy and applied it to an independent validation cohort. The BEST2 study is registered with ISRCTN, number 12730505. FINDINGS: The discovery cohort consisted of 468 patients with Barrett's oesophagus and intestinal metaplasia. Of these, 376 had no dysplasia and 22 had high-grade dysplasia or intramucosal adenocarcinoma. In the discovery cohort, a model with high classification accuracy consisted of glandular atypia, P53 abnormality, and Aurora kinase A positivity, and the interaction of age, waist-to-hip ratio, and length of the Barrett's oesophagus segment. 162 (35%) of 468 of patients fell into the low-risk category and the probability of being a true non-dysplastic patient was 100% (99% CI 96-100) and the probability of having high-grade dysplasia or intramucosal adenocarcinoma was 0% (0-4). 238 (51%) of participants were classified as of moderate risk; the probability of having high-grade dysplasia was 14% (9-21). 58 (12%) of participants were classified as high-risk; the probability of having non-dysplastic endoscopic biopsies was 13% (5-27), whereas the probability of having high-grade dysplasia or intramucosal adenocarcinoma was 87% (73-95). In the validation cohort (65 patients), 51 were non-dysplastic and 14 had high-grade dysplasia. In this cohort, 25 (38%) of 65 patients were classified as being low-risk, and the probability of being non-dysplastic was 96·0% (99% CI 73·80-99·99). The moderate-risk group comprised 27 non-dysplastic and eight high-grade dysplasia cases, whereas the high-risk group (8% of the cohort) had no non-dysplastic cases and five patients with high-grade dysplasia. INTERPRETATION: A combination of biomarker assays from a single Cytosponge sample can be used to determine a group of patients at low risk of progression, for whom endoscopy could be avoided. This strategy could help to avoid overdiagnosis and overtreatment in patients with Barrett's oesophagus. FUNDING: Cancer Research UK.

Appendiceal metastasis 10 years following 'curative' resection for low-grade primary endometrial carcinoma.

Metastasis of primary endometrial adenocarcinoma to unusual sites has been occasionally reported. However, the authors believe this to be the first case report of metastasis to the appendix. This occurred more than 10 years after curative resection, and presented as sepsis with an intra-abdominal focus.