Selective Resection of Type 1 Gastric Neuroendocrine Neoplasms and the Risk of Progression in an Endoscopic Surveillance Programme.

BACKGROUND: Current guidance for type 1 gastric neuroendocrine neoplasms (gNENs) recommends either resection of all visible lesions or selective resection of gNENs >10 mm. We adopt a selective strategy targeting lesions approaching 10 mm for endoscopic mucosal resection (EMR) and provide surveillance for smaller lesions. OBJECTIVES: This study aimed to describe the incidence of type 1 gNENs requiring endoscopic/surgical resection and the risk of disease progression (both considered significant disease) on endoscopic surveillance. The secondary objective was to assess the risk factors for disease progression during surveillance and the incidence of gastric dysplasia/adenoma/adenocarcinoma. METHODS: We collected consecutive patients with type 1 gNENs and obtained demographic and clinical data through the electronic patient record. RESULTS: In our cohort of 57 patients, 12 patients had EMR at index gastroscopy; 7 patients had surgery (4: large/multiple gNENs and 3: nodal metastases) (5.2% [3/57] risk of nodal metastases); and a patient with nodal and liver metastases (1.8% [1/57] risk of distant metastases). The prevalence of gastric adenocarcinoma in our study was 3.5% with an incidence rate of 9.59 per 1,000 persons per year. For patients undergoing surveillance, 29.5% (13/44) of patients progressed requiring resection. Serum gastrin was significantly higher in patients who progressed to resection (p value = 0.023). CONCLUSION: We concluded that up to a third of patients with type 1 gNENs have significant disease requiring resection. Hence, endoscopic surveillance and resect strategy would benefit patients.

Prevalence of coexisting autoimmune thyroidal diseases in coeliac disease is decreasing.

BACKGROUND: Coeliac disease (CD) is associated with an increased risk of other immune-mediated conditions. Aim: To investigate the prevalence of coexistent immune-mediated diseases in CD patients, and changes in the prevalence of autoimmune thyroidal diseases over the last 50 years. METHODS: Medical record data were collected retrospectively from 749 CD patients in Ireland. Prevalence of autoimmune diseases was compared with previously published results from general populations. Patients were divided into four groups based on the year of diagnosis to analyse changes in the prevalence of autoimmune thyroidal disease over time. RESULTS: Median age at the time of CD diagnosis was 56 years (range 18-91 years). A total of 233 (31.1%) patients had a coexistent immune-mediated condition (IMC). Autoimmune thyroidal diseases were seen in 149 (19.9%) patients, hypothyroidism in 110 (14.7%), type 1 diabetes in 27 (3.6%), psoriasis in 20 (2.7%), inflammatory bowel disease in 14 (1.9%) and rheumatoid arthritis in 12 (1.6%). All conditions were more common in CD patients than in the general population. Type 1 diabetes was diagnosed mainly before CD, whereas there was no such trend in other conditions. Autoimmune thyroidal diseases became less common in female CD patients over time. CONCLUSIONS: Prevalence of autoimmune diseases is increased in adult CD patients compared with the general population. However, concomitant autoimmune thyroidal diseases became less common over time in women.

Patterns of splenic arterial enhancement on computed tomography are related to changes in portal venous pressure.

OBJECTIVES: One of the striking features of splenic imaging is variable heterogeneous gyriform arterial enhancement on dynamic computed tomography (CT). We speculated that these patterns of arterial enhancement may reflect changes in splenic micro-circulation related to changes in portal venous pressure. PATIENTS AND METHODS: To test this hypothesis, we evaluated arterial phase CT scans performed before and after liver transplantation (n=91), as this is the most effective way of alleviating portal hypertension. We developed novel grading systems to assess heterogeneity. Two control groups were used: patients with cirrhosis undergoing transarterial chemoembolization (TACE) (n=28) and patients with cirrhosis on the liver transplant waiting list who had repeated CT scans (n=28). RESULTS: Splenic arterial heterogeneity increased in 55% of transplant patients compared with 14% in the TACE patients and 4% in the waiting list patients (P<0.0001). Mean Hounsfield units in areas of splenic enhancement were 71.7±2 before transplant and 90.1±2.5 after transplant (P<0.01). In contrast, there were no significant changes following TACE (86.3±4.2 vs. 83.5±4.5; P=NS) or in waiting list patients (80.9±4.6 vs. 73.8±3.7; P=NS). CONCLUSION: We have shown the heterogeneous gyriform enhancement patterns significantly increase following liver transplantation but not after TACE or in waiting list patients. We suggest that these changes are due to the reduction in portal venous pressure and likely reflect changes in splenic micro-circulation. These changes may be important in the pathophysiology of hypersplenism.

Diagnosis and Management of Upper Gastrointestinal Neuroendocrine Tumors.

Upper gastrointestinal neuroendocrine tumors (NETs) are rare tumors which are increasingly recognised by practising endoscopists. After confirmation by endoscopic biopsies of these focal lesions, many questions may arise. As NETs are less frequently encountered compared to other malignancies or gastrointestinal pathology, many endoscopists may not fully understand the natural history, diagnosis and management of these tumors. In this review, we aim to update the practising endoscopist on the key clinical features and management of patients with upper gastrointestinal NET.

Thrombocytopenia, Platelet Transfusion, and Outcome Following Liver Transplantation.

Thrombocytopenia affects patients undergoing liver transplantation. Intraoperative platelet transfusion has been shown to independently influence survival after liver transplantation at 1 and 5 years. We examined the impact of thrombocytopenia and intraoperative platelet transfusion on short-term graft and overall survival after orthotopic liver transplantation (OLT). A total of 399 patients undergoing first OLT were studied. Graft and overall survival in patients with different degrees of thrombocytopenia and with or without intraoperative platelet transfusion were described. The degree of thrombocytopenia prior to OLT did not affect graft or overall survival after transplant. However, graft survival in patients receiving platelets was significantly reduced at 1 year (P= .023) but not at 90 days (P= .093). Overall survival was significantly reduced at both 90 days (P= .040) and 1 year (P= .037) in patients receiving platelets. We conclude that a consistently lower graft and overall survival were observed in patients receiving intraoperative platelet transfusion.

Spleen stiffness can non-invasively assess resolution of portal hypertension after liver transplantation.

BACKGROUND & AIMS: Spleen stiffness can be measured by transient elastography. Recent studies have shown that spleen stiffness correlates with hepatic venous pressure gradient and can predict oesophageal varices. Elevated spleen stiffness in cirrhosis has been attributed to splenic tissue hyperplasia and fibrosis, portal hypertension and its consequent hyperdynamic circulation. The aim of this study was to investigate changes to spleen stiffness after orthotopic liver transplantation (OLT) when portal hypertension resolves. METHODS: Twenty-one patients awaiting OLT were studied prospectively, while 11 post-transplant patients were recruited as controls. Spleen and liver stiffness were measured with Fibroscan before and at 2-8 weeks after OLT. Criteria applied for spleen stiffness measurement were similar to liver stiffness (≥10 measurements; ≥60% success rate; interquartile range, IQR <30% of median). RESULTS: Spleen stiffness was significantly higher before OLT compared to post-transplant patients [75.0 (63.9-75.0) kPa vs. 28.4 (22.0-37.5) kPa; P < 0.0001]. For patients awaiting OLT, 90% (19/21) had oesophageal varices (endoscopically or radiologically). In patients who underwent liver transplantation, spleen stiffness decreased significantly from a median of 75.0 (62.0-75.0) kPa before OLT, to 41.9 (27.0-47.4) kPa at 2 weeks after transplant and 32.9 (29.1-38.0) kPa in the subsequent 4-8 weeks after OLT (P < 0.0001). As expected, liver stiffness measurements reduced from 39.3 (24.9-75.0) kPa to 8.6 (6.8-11.8) kPa in patients receiving OLT (P = 0.0004). CONCLUSIONS: Spleen stiffness can non-invasively assess changes in portal pressure after liver transplantation and decreases significantly when portal hypertension resolves.

Homozygosity for HLA group 2 alleles predicts treatment failure with interferon-α and ribavirin in chronic hepatitis C virus genotype 1 infection.

Host genetic factors influence treatment responses to antiviral therapy in chronic hepatitis C virus (HCV) infection. We retrospectively investigated associations between host genetic markers and treatment-induced virologic responses to dual therapy with interferon-α and ribavirin in chronically infected HCV genotype 1 (g1)- and genotype 3 (g3)-infected individuals. A total of 171 patients (89 HCV g1 and 82 HCV g3 infected) were investigated for genetic markers influencing treatment-induced sustained virologic response (SVR). Overall, SVR was observed for 46/89 (52%) HCV g1- and 57/82 (70%) HCV g3-infected patients. Of the 4 interleukin 28B (IL28B) single-nucleotide polymorphisms (SNPs), rs12979860 was the host genetic marker most significantly associated with failure to achieve an SVR in HCV g1-infected individuals [P=3.83×10(-4); odds ratio (OR)=5.61; confidence interval (CI)=2.07-15.18] and gave a positive predictive value for treatment failure of 81.3% for minor homozygotes (TT). Using additive (P=3.54×10(-4)) and dominant models (P=3.83×10(-4)), a dosage effect of the T allele was observed, with the dominance term not significant for this SNP. Logistic regression showed an association between HLA-C1/C1 and rapid virologic response in HCV g1 infections with an OR relative to the heterozygote of 10.0 (95% CI: 1.6-62.5, P=0.014). HLA-C2 homozygosity was a significant predictor of nonresponse to treatment in HCV g1-infected individuals (P=0.023).

A prospective 52 week mucosal healing assessment of small bowel Crohn's disease as detected by capsule endoscopy.

BACKGROUND: Mucosal healing is increasingly recognised as an important treatment goal in Crohn's disease (CD). Data from colonic disease shows improved long-term outcomes in patients achieving complete mucosal healing. Little is currently known of this with regard to ileitis which is increasingly diagnosed using capsule endoscopy (SBCE). This is the first study to prospectively assess mucosal healing and deep remission rates following 52 weeks of therapy in a cohort of symptomatic small bowel CD patients commencing immunomodulator or biologic therapy. METHODS: Baseline demographics, quality of life questionnaires and Harvey Bradshaw Index were collected along with C-reactive protein & calprotectin. Capsule endoscopy Crohn's disease activity (CECDAI) index was used to assess ileitis severity. All parameters were reassessed at week 52. Results at baseline & week 52 were compared using univariate analysis, p < 0.05 considered significant. RESULTS: In total, 108 capsule procedures were performed on 43 patients. Based on the CECDAI, 39 (90%) demonstrated active small bowel CD at baseline with 28 (65%) undergoing 52 week assessment. In total, 12 (42%) participants achieved complete mucosal healing and deep remission by 52 week assessment (p<0.0001 95% CI -0.62 to -0.22). Despite overall impressive mucosal healing rates, patients with strictures were less likely to demonstrate a decrease in CECDAI and were more likely to have symptoms. CONCLUSION: In patients with active small bowel CD symptomatic and biochemical response to treatment appears to be mirrored by endoscopic remission in 42% of individuals. Strictures identified prior to therapy appear to be a poor indicator for success of treatment.

Effects of portal hypertension on contractility of rat spleen.

Portal hypertension induces changes in vascular responses to vasoconstrictors. However, the effects of portal hypertension on splenic contraction have not previously been investigated. In partial portal vein ligated (PVL) and sham-operated rats, we examined the splenic contractile responses to cumulative concentrations of noradrenaline and KCl. In PVL rats, the potency of noradrenaline in producing splenic contraction was significantly increased (pEC50 of 5.88 ± 0.08), as compared to sham (5.40 ± 0.06; p<0.001). In the presence of prazosin (10(-8)M), there was a significant rightward shift in the noradrenaline concentration response curve but the shift was greater for PVL, so that in the presence of prazosin there was no significant difference between PVL and sham animals in the potency of noradrenaline. Prazosin produced a significantly greater shift of noradrenaline potency in spleen from PVL (pKB of 8.88 ± 0.06) (n=6) than from sham animals (8.51 ± 0.08, n=6), demonstrating that the α1-adrenoceptor mediated component is greater in spleen from PVL. In the presence of prazosin (10(-8)M) the residual response is non-α1-adrenoceptor mediated, presumably α2-adrenoceptor mediated, and this response did not differ between sham and PVL. The maximum splenic contraction did not significantly differ between sham and PVL rats for either agonist. In conclusion, noradrenaline potency in contracting the rat spleen was significantly increased in tissues from PVL rats. The increased potency of prazosin suggests a greater predominance of α1-adrenoceptors in spleen of PVL rats, as prazosin has lower potency at α2-adrenoceptors.

Spontaneous clearance of hepatitis C infection after liver transplantation from IL28B rs12979860 CC donors.

Genetic polymorphisms adjacent to IL28B have been previously associated with spontaneous clearance of hepatitis C virus (HCV) and a higher rate of sustained virological response to interferon-based treatment in HCV genotype 1-infected patients. A recent study has shown that patients with the CC genotype of the rs12979860 single nucleotide polymorphism upstream from the IL28B gene are more likely to clear HCV spontaneously relative to the CT or TT genotype. In the liver transplant cohort, HCV recurs almost universally in patients with detectable HCV RNA at the time of transplantation. The spontaneous clearance of HCV infection after transplant is very rare. We report two cases of spontaneous clearance of HCV genotype 1 infection after liver transplantation from homozygous IL28B CC donors. This finding may be explained by alterations in the host immune responses to HCV after transplantation with a CC donor liver, which has potential implications for donor selection in HCV-positive recipients.

Using the MDRD value as an outcome predictor in emergency medical admissions.

BACKGROUND: Both physiological- and laboratory-derived variables, alone or in combination, have been used to predict mortality among acute medical admissions. Using the Modification of Diet in Renal Disease (MDRD) not as an estimate of glomerular filtration rate but as an outcome predictor for hospital mortality, we examined the relationship between the MDRD value and in-hospital death during an emergency medical admission. METHODS: An analysis was performed on all emergency medical patients admitted between 1 January 2002 and 31 December 2008, using the hospital in-patient enquiry system, linked to the patient administration system and laboratory datasets. Hospital mortality (any in-patient death within 30 days) was obtained from a database of deaths occurring during the same period under physicians participating in the 'on-call' roster. Logistic regression was used to calculate unadjusted and adjusted odds ratios (OR) and 95% confidence intervals (CI) for MDRD value. RESULTS: Univariate analysis identified those with MDRD value of <60 as possessing increased mortality risk. Their 30-day mortality rate was 21.63 versus 4.35% for patients without an abnormal value (P < 0.0001) with an OR of 6.07 (95% CI's 5.49, 6.73: P < 0.001). After adjustment for 12 other outcome predictors including comorbidity, the OR was 4.63 (4.08, 5.25: P < 0.0001). Using the Kidney Disease Outcomes Quality Initiative (KDOQI) class, the respective mortality rates by 30 days increased with a lower MDRD value, from 2.8% in KDOQI Class 1 to 48.6% in KDOQI Class 5. Outcome prediction of in-hospital death, at 5 and 30 days with the MDRD, yielded areas under the receiver operator curves of 0.84 (0.83, 0.84) and 0.77 (0.77, 0.78). CONCLUSIONS: Many factors predict survival following an emergency medical admission. The MDRD value offers a novel readily available and reliable estimate of mortality risk.