Guidelines for the management of gastroenteropancreatic neuroendocrine (including carcinoid) tumours (NETs).

These guidelines update previous guidance published in 2005. They have been revised by a group who are members of the UK and Ireland Neuroendocrine Tumour Society with endorsement from the clinical committees of the British Society of Gastroenterology, the Society for Endocrinology, the Association of Surgeons of Great Britain and Ireland (and its Surgical Specialty Associations), the British Society of Gastrointestinal and Abdominal Radiology and others. The authorship represents leaders of the various groups in the UK and Ireland Neuroendocrine Tumour Society, but a large amount of work has been carried out by other specialists, many of whom attended a guidelines conference in May 2009. We have attempted to represent this work in the acknowledgements section. Over the past few years, there have been advances in the management of neuroendocrine tumours, which have included clearer characterisation, more specific and therapeutically relevant diagnosis, and improved treatments. However, there remain few randomised trials in the field and the disease is uncommon, hence all evidence must be considered weak in comparison with other more common cancers.

Systemic sclerosis associated pulmonary hypertension: improved survival in the current era.

OBJECTIVES: To measure survival, haemodynamic function and functional class in patients with systemic sclerosis associated pulmonary arterial hypertension (SSc-PAH) in two treatment eras. METHODS: Six year longitudinal study of 92 consecutive patients with SSc-PAH diagnosed by cardiac catheterisation. Data were collected both prospectively and retrospectively. Patients were given basic treatment (diuretics, digoxin, oxygen and warfarin). Where clinically indicated, a prostanoid was used as advanced treatment (historical control group). From 2002, the range of treatments available expanded to include bosentan, which was generally the preferred treatment (current treatment era group). Survival was measured from the date of diagnosis of pulmonary hypertension by cardiac catheterisation. Six minute walking distance and haemodynamic function were measured at the time of diagnosis and at least one month after treatment was started. RESULTS: The historical control group comprised 47 patients, all of whom received basic treatment; 27 of these were also treated with prostanoids. The current treatment era group comprised 45 patients, all of whom received bosentan as preferred treatment. Kaplan-Meier survival in the historical control group was 68% at one year and 47% at two years. Survival in the current treatment era group was 81% and 71% (p = 0.016) at one and two years, respectively. Pulmonary vascular resistance increased in the historical control group (by 147 dyn.s.cm(-5)), whereas in the current treatment era group, it remained stable over an average of nine months (decrease of 16 dyn x s x cm(-5), p < 0.006). CONCLUSION: Survival of selected patients with SSc-PAH has improved in the current treatment era. In contrast to patients treated historically with basic drugs and prostanoids, patients treated in the current treatment era had improved survival associated with a lack of deterioration in cardiac haemodynamic function.

Echocardiography and pulmonary function as screening tests for pulmonary arterial hypertension in systemic sclerosis.

OBJECTIVE: A prospective study to evaluate echocardiography and gas transfer (DLCO) by comparison with cardiac catheterization in discriminating between patients with and without systemic sclerosis-associated pulmonary arterial hypertension (SScPAH). METHOD: A total of 137 (52 with and 85 without pulmonary fibrosis) had echocardiography and lung function tests within 3 months of their definitive invasive study. RESULTS: At cardiac catheterization 99 of these patients were found to have PAH, while PAH was excluded in 38. Echocardiographically estimated tricuspid gradient (TG) showed a moderate positive correlation (r(2) = 0.44, P<0.005) with both mean pulmonary pressure and invasively determined tricuspid gradient. DLCO showed a weak correlation (r(2 )= 0.09, P = 0.006), when compared with mean pulmonary arterial pressure. In total, 97% of patients with an echocardiographically determined TG of > 45 mmHg were found to have pulmonary hypertension at catheterization. However, no threshold could be defined with either screening test that safely excluded PAH. CONCLUSIONS: The positive predictive accuracy of currently used non-invasive tests are adequate for the diagnosis of advanced PAH provided sufficiently high thresholds (TG > 45 mmHg or DLCO < 55% predicted) are used. These tests cannot be relied upon to exclude pulmonary hypertension where pre-test probability is high.

Prevalence and outcome in systemic sclerosis associated pulmonary arterial hypertension: application of a registry approach.

OBJECTIVE: To determine the prevalence of systemic sclerosis associated pulmonary arterial hypertension (SScPAH), evaluate outcome, and identify predictors of mortality in a large patient cohort. METHODS: A prospective four year follow up study of 794 patients (722 from our own unit and 72 referrals). All patients screened for PAH using a combination of echocardiography, lung function testing, and clinical assessment. Patients with suspected raised pulmonary artery systolic pressures of >35 mm Hg, carbon monoxide transfer factor (TLCO) <50% predicted, or a precipitous fall in TLCO >20% over a one year period with no pulmonary fibrosis, and patients with SSc with breathlessness with no pulmonary fibrosis found were investigated with right heart catheterisation. All patients with SScPAH were treated in accordance with current best practice. RESULTS: The prevalence of PAH was 12% (89/722) by right heart catheter. The survival was 81%, 63%, and 56% at 1, 2, and 3 years from the diagnosis (in 89 patients from our own cohort and 59/72 referrals). Haemodynamic indices of right ventricular failure--raised mRAP (hazard ratio 21), raised mPAP (hazard ratio 20), and low CI (hazard ratio 11) predicted an adverse outcome There was no significant difference in survival between patients with SScPAH with (n=40) and without (n=108) pulmonary fibrosis (p=0.3). CONCLUSIONS: The prevalence of SScPAH in this cohort was similar to that of other catheter based studies and lower than that of previous echo based studies. The 148 patients with SScPAH actively treated had comparable outcomes to those of the cohorts with primary pulmonary hypertension. A high mRAP was the strongest haemodynamic predictor of mortality. To improve prognosis, future treatments need to be implemented at an earlier disease stage to prevent right ventricular decompensation.

Atrial thrombus and central venous dialysis catheters.

A native arteriovenous fistula is the first choice for hemodialysis access. Despite improved catheter designs and the use of internal jugular veins, thrombotic complications still occur when tunneled central venous catheters are used as an alternative. Although right atrial thrombus (RAT) is a well-characterized complication of long-term central venous cannulation, particularly when used for parenteral nutrition and chemotherapy in pediatric practice, only 9 reported cases previously have been associated with the long-term use of central venous catheters for hemodialysis. We report five cases of RAT seen at our unit between 1994 and 1998 in patients who had been dialyzed using tunneled catheters. In four of five cases, the diagnosis was made during the investigation of hemoptysis or dyspnea. In the fifth case, a screening transthoracic echocardiogram revealed the thrombus. Three of five of the patients suffered pulmonary emboli, and a fourth patient had an unexplained electromechanical dissociation cardiac arrest without definite evidence of pulmonary embolus. Our experience suggests that anticoagulated patients with RAT remain at risk of pulmonary embolism. One of our patients successfully underwent atrial thrombectomy. In four of five of our cases and four of nine cases in the literature, the central venous catheter tip was within the right atrium. Positioning of the central venous catheter tip low down in the superior vena cava or in the right atrium has been advocated to improve dialysis adequacy and to reduce the incidence of catheter thrombosis. However, placement of the catheter tip within the right atrium may be associated with an increased risk of RAT.

Prognostic value of stress echocardiography in women with high (> or = 80%) probability of coronary artery disease.

OBJECTIVE: To assess the prognostic significance of stress echocardiography in women with a high probability of coronary artery disease (CAD). SETTING: Secondary and tertiary cardiology unit at a university teaching hospital. PARTICIPANTS: A total of 135 women (mean (SD) age 63 (9) years) with pre-test probability of CAD > or = 80% were selected from a database of patients investigated by treadmill or dobutamine stress echocardiography between 1995 and 1998. MAIN OUTCOME MEASURES: Patients were followed up for occurrence of subsequent cardiac events (cardiac death, myocardial infarction, admission with unstable angina, and revascularisation) using a structured telephone interview and case note review. RESULTS: Each patient had between two and seven (mean 3.5) CAD risk factors and pre-test probability of CAD > or = 80%. Ninety three patients (68.9%) had negative stress echocardiography. Mean (SD) follow up was 20.1 (8.5) months. There were six events in the positive stress echocardiography group (two cardiac deaths, one unstable angina, three revascularisations), and one event in the negative stress echocardiography group. Cox regression analysis showed positive stress echocardiography (p = 0.02) and age (p = 0.03) to be the only univariate predictors and positive stress echocardiography to be the only independent predictor of future cardiac events (relative risk 8.9, confidence interval 1.0 to 76.5, p = 0.04). Cumulative event free survival to 38 months was 98% in the negative stress echocardiography and 50.7% in the positive stress echocardiography groups. CONCLUSION: In women with high pre-test likelihood of CAD: (1) negative stress echocardiography identifies a subgroup with low risk of cardiac events who do not require further invasive investigation and (2) positive stress echocardiography identifies a subgroup with increased risk of subsequent cardiac events.

Pulmonary hypertension in systemic sclerosis: risk factors for progression and consequences for survival.

OBJECTIVE: To assess the rate of progression of pulmonary hypertension (PHT) in systemic sclerosis (SSc) and its bearing on mortality. METHODS: A retrospective record review of 930 patients with SSc attending a specialist centre was carried out. Those at risk for both idiopathic and secondary PHT were assessed by serial Doppler echocardiography. Mortality data were reviewed. RESULTS: The cumulative prevalence of PHT was 13%. Pressures remained static in most cases. The mortality among those with a single pressure reading of 30 mmHg or higher was 20% at 20 months. An increased mortality risk was associated with high initial pressures and rising pressures. Rapid pressure rises occurred more frequently in limited than in diffuse SSC. CONCLUSIONS: The prevalence of PHT in SSc is high and the detection of PHT at any time in the disease course is associated with substantial mortality. These results demonstrate the value of echocardiographic screening for PHT in all patients with SSC.

Prognostic value of negative dobutamine stress echo in women with intermediate probability of coronary artery disease.

Women with an intermediate pretest probability of coronary artery disease represent a significant proportion of patients referred for the investigation of chest pain. Dobutamine stress echocardiography can be used to restratify these patients into a low-risk group without resorting to cardiac catheterization.

A case of spontaneous coronary artery disease regression.

Coronary angiographic trials have demonstrated that lowering cholesterol can slow the progression of atherosclerosis, limit the formation of new lesions and enhance atherosclerotic regression together with reducing the incidence of clinical events (Waters D, 1996). Spontaneous regression of coronary atherosclerotic lesions is rare. We report the case of a patient with a severe within-stent restenotic lesion whose coronary disease spontaneously regressed 12 months after initial diagnosis, allowing for medical treatment of symptoms rather than repeated intervention. (Int J Cardiovasc Interventions 1999; 2: 121-123)