Surgical and medical management of small bowel gastrointestinal stromal tumors: A report of the Dutch GIST registry.

BACKGROUND: A cohort of 201 patients with small bowel gastrointestinal stromal tumors (GIST) treated between January 1st, 2009 and December 31st, 2016 in five GIST expertise centers in the Netherlands was analyzed. Goal of this study was to describe the clinical, surgical and pathological characteristics of this rare subpopulation of GIST patients, registered in the Dutch GIST registry. METHODS: Clinical outcomes and risk factors of patients with small bowel GIST who underwent surgery or treated with systemic therapy were analyzed. A classification was made based on disease status at diagnosis (localized vs. metastasized). RESULTS: 201 patients with small bowel GIST were registered of which 138 patients (69%) were diagnosed with localized disease and 63 patients (31%) with metastatic disease. Approximately 19% of the patients had emergency surgery, and in 22% GIST was an accidental finding. In patients with high risk localized disease, recurrence occurred less often in patients who received adjuvant treatment (4/32) compared to patients who did not (20/31, p < 0.01). Disease progression during palliative imatinib treatment occurred in 23 patients (28%) after a median of 20.7 (range 1.8-47.1) months. Ongoing response was established in 52/82 patients on first line palliative treatment with imatinib after a median treatment time of 30.6 (range 2.5-155.3) months. CONCLUSION: Patients with small-bowel GIST more frequently present with metastatic disease when compared to patients with gastric GIST in literature. We advocate for Prospective registration of these patients and investigate the use of surgery in patients with limited metastatic disease.

Pregnancy-related myocardial infarction.

INTRODUCTION: The risk of acute myocardial infarction in young women is low, but increases during pregnancy due to the physiological changes in pregnancy, including hypercoagulability. Ischaemic heart disease during pregnancy is not only associated with increased maternal morbidity and mortality, but also with high neonatal complications. Advancing maternal age and other risk factors for cardiovascular diseases may further increase the risk of ischaemic heart disease in young women. METHODS: We searched the coronary angiography database of a Dutch teaching hospital to identify women with acute myocardial infarction who presented during pregnancy or postpartum between 2011 and 2013. RESULTS: We found two cases. Both women were in their early thirties and both suffered from myocardial infarction in the postpartum period. Acute myocardial infarction was due to coronary stenotic occlusion in one patient and due to coronary artery dissection in the other patient. Coronary artery dissection is a relatively frequent cause of myocardial infarction during pregnancy. Both women were treated by percutaneous coronary intervention and survived. CONCLUSION: Physicians should be aware of the increased risk of myocardial infarction when encountering pregnant or postpartum women presenting with chest pain.

Statistical controversies in clinical research: building the bridge to phase II-efficacy estimation in dose-expansion cohorts.

BACKGROUND: Regulatory agencies and others have expressed concern about the uncritical use of dose expansion cohorts (DECs) in phase I oncology trials. Nonetheless, by several metrics-prevalence, size, and number-their popularity is increasing. Although early efficacy estimation in defined populations is a common primary endpoint of DECs, the types of designs best equipped to identify efficacy signals have not been established. METHODS: We conducted a simulation study of six phase I design templates with multiple DECs: three dose-assignment/adjustment mechanisms multiplied by two analytic approaches for estimating efficacy after the trial is complete. We also investigated the effect of sample size and interim futility analysis on trial performance. Identifying populations in which the treatment is efficacious (true positives) and weeding out inefficacious treatment/populations (true negatives) are competing goals in these trials. Thus, we estimated true and false positive rates for each design. RESULTS: Adaptively updating the MTD during the DEC improved true positive rates by 8-43% compared with fixing the dose during the DEC phase while maintaining false positive rates. Inclusion of an interim futility analysis decreased the number of patients treated under inefficacious DECs without hurting performance. CONCLUSION: A substantial gain in efficiency is obtainable using a design template that statistically models toxicity and efficacy against dose level during expansion. Design choices for dose expansion should be motivated by and based upon expected performance. Similar to the common practice in single-arm phase II trials, cohort sample sizes should be justified with respect to their primary aim and include interim analyses to allow for early stopping.

Less negative appendectomies due to imaging in patients with suspected appendicitis.

BACKGROUND: The optimal diagnostics and treatment of acute appendicitis continues to be a challenge. We evaluated the implementation of the guideline "diagnostics and treatment in acute appendicitis" in 2010. This guideline states that, in every patient with clinically suspected acute appendicitis, an ultrasonography or CT scan is advised to confirm the diagnosis before surgery. PATIENTS AND METHODS: We selected all consecutive patients with acute appendicitis in our hospital in the years 2008 and 2011. We compared the use of imaging and the operation results in both years. RESULTS: In 2008, 228 patients were treated for acute appendicitis. In 43 %, imaging was performed. In 2011, 238 patients were treated; in 99 % of the cases, imaging was performed. A decrease in patients with negative appendectomy was seen from 19 % in 2008 to 5 % in 2011. Financial analysis showed a reduction in costs favoring 2011. CONCLUSIONS: The increased use of pre-operative imaging in patients with suspected acute appendicitis resulted in a cost-effective way to decrease the number of patients with negative appendectomies.

In-hospital mortality and three-year survival after repaired acute type A aortic dissection.

Background. The results of acute type A dissection (AAD) surgery in the Netherlands are largely unknown, as was recently stated in a report by the Health Council of the Netherlands. In order to gain more insight into the Dutch situation we investigated predictors of in-hospital mortality of surgically treated AAD patients and assessed threeyear survival.Methods. 104 consecutive patients undergoing surgery for AAD in a 16-year period (1990-2006) were evaluated. Preoperative and intraoperative variables were analysed to identify predictors of early mortality.Results. Preoperative malperfusion (limb ischaemia or mesenteric ischaemia) was present in 15.4%, shock in 18.3%, and 6.7% were operated under cardiac massage. Marfan syndrome was present in four patients and four patients had a bicuspid aortic valve. In-hospital mortality was 22.1%. Seven patients died intraoperatively; other causes of inhospital mortality were major brain damage in ten patients, multiple organ failure in three patients, low cardiac output in two patients and sudden cardiac death in one patient. Multivariate logistic regression revealed preoperative malperfusion (p=0.004) to be the only independent predictor of in-hospital mortality. Three-year survival was 68.8+/-4.7% (including hospital mortality). Hospital survivors had a three-year survival of 88.3+/-3.9%.Conclusion. In-hospital mortality of our patients (22.1%) is comparable with the results of larger case series published in the literature. Prognosis after successful surgical treatment is relatively good with a three-year survival of 88.3% in our series. (Neth Heart J 2009;17:226-31.).

The many faces of aggressive aortic pathology: Loeys-Dietz syndrome.

BACKGROUND: Loeys-Dietz syndrome (LDS) is a newly recognised disorder of connective tissue which shares overlapping features with Marfan syndrome (MFS) and the vascular type of Ehlers-Danlos syndrome, including aortic root dilatation and skin abnormalities. It is clinically classified into types 1 and 2. LDS type 1 can be recognised by craniofacial characteristics, e.g. hypertelorism, bifid uvula or cleft palate, whereas these are absent in LDS type 2. It is important to recognise LDS because its vascular pathology is aggressive. We describe nine LDS patients from four families, relate their features to published cases, and discuss important aspects of the diagnosis and management of LDS in order to make clinicians aware of this new syndrome. RESULTS: Characteristics found in the majority of these LDS patients were aortic root dilatation, cleft palate and/or a bifid/abnormal uvula. CONCLUSION: Because aortic dissection and rupture in LDS tend to occur at a young age or at aortic root diameters not considered at risk in MFS, and because the vascular pathology can be seen throughout the entire arterial tree, patients should be carefully followed up and aggressive surgical treatment is mandatory. Clinicians must therefore be aware of LDS as a cause of aggressive aortic pathology and that its distinguishing features can sometimes be easily recognised. (Neth Heart J 2008;16:299-304.).

EuroSCORE predicts poor health-related physical functioning six month postcoronary artery bypass graft surgery.

AIM: The objectives of this study are to test whether the European system of cardiac-operative risk evaluation score (EuroSCORE) is associated with preoperative health-related quality of life (HRQoL), and whether it is a predictor of mental and physical health-related quality of life six months after coronary artery bypass grafting (CABG). METHODS: A longitudinal observational study was carried out among 181 patients who underwent CABG. Physical and mental domains of quality of life were measured using SF-36 and risk stratification was estimated using the EuroSCORE. A post hoc test (with Bonferroni correction) was used to determine whether EuroSCORE was associated with preoperative HRQoL, LOS and postoperative rate of complications. Hierarchical regression analysis was performed to explore the associations between EuroSCORE, postoperative events and postoperative HRQoL. RESULTS: EuroSCORE is associated with physical functioning before and after CABG and a higher EuroSCORE is a predictor of poor physical functioning and not a predictor of the mental domains of quality of life, while smoking predicted bodily pain after CABG. Furthermore, readmission within six weeks after discharge was a predictor of poor physical functioning, physical role and general health. Moreover, post hoc tests showed statistically significant and clinically relevant differences in physical functioning between low-risk and high-risk EuroSCORE classes, and between medium and high classes at baseline and six months after CABG. High-risk patients had more perioperative complications and longer lengths of stay, as compared to low-risk patients. CONCLUSION: EuroSCORE is a predictor of poor self-reported physical functioning six months after CABG and is not a predictor of mental functioning.

Hybrid approach for complex coronary artery and valve disease: a clinical follow-up study.

BACKGROUND: For patients suffering from complex coronary artery disease (CAD) with or without concomitant valve disease, no evidence is available in the current guidelines to propose a predefined treatment regimen. We sought to assess the clinical impact of an unconventional or extended definition of the hybrid approach that combines percutaneous coronary intervention (PCI) and cardiac surgery in subjects suffering from severe solitary CAD or combined with valve disease. METHODS AND RESULTS: Between July 2002 and August 2004, 18 consecutive patients with complex CAD with or without significant valve disease who qualified for a hybrid approach were enrolled in a clinical follow-up study. Four patients eventually did not complete the proposed interventions. One patient refused treatment after inclusion, one patient died before treatment could be undertaken and two patients died after surgery but before PCI. In the other 14 cases combined treatment was technically successful. After a mean follow-up period of 15alpha5 months two patients had died, one due to sudden cardiac death and one of a noncardiac cause. No other major adverse clinical events were reported. A marked increase in quality of life was reported in those alive. CONCLUSION: Hybrid approach had a favourable long-term outcome in patients with complex cardiovascular disease undergoing successful treatment; however, this was observed at the expense of significant periprocedural mortality in these high-risk subjects. Therefore we believe that hybrid approaches may provide an alternative for selected cases. (Neth Heart J 2007;15:329-4.).

Long-term clinical outcome of patients with diabetes proposed for coronary revascularisation.

BACKGROUND: The optimal method of revascularisation in diabetic patients with coronary artery disease (CAD) remains controversial. It was our aim to evaluate long-term outcome in diabetic patients with CAD in daily practice, in whom an invasive approach was considered. METHODS: A prospective follow-up study of patients with CAD in whom a coronary revascularisation procedure was considered. Follow-up data were obtained on the vital status up to ten years after inclusion. RESULTS: Of the 872 included patients, a total of 107 patients (12%) had diabetes. Patients with diabetes were older and more frequently female. Long-term mortality was higher in diabetics than nondiabetics (36 vs 25%, p = 0.01). This association was observed in both medically treated patients (65 vs 31%, p = 0.01) and in those treated by percutaneous coronary intervention (41 vs 24%, p = 0.02). There was, however, no difference in mortality in diabetes vs nondiabetes patients after coronary artery bypass grafting (24 vs 24%, p = 0.89). Multivariate analysis did not change these findings. CONCLUSION: Diabetic patients with significant CAD had a higher long-term mortality compared with patients without diabetes. In patients with diabetes, survival was highest after coronary artery bypass grafting and appeared to be comparable between diabetic and nondiabetic patients. Complete revascularisation may decrease the influence of diabetes on survival.

Long-term outcome after heart transplantation performed in the University Medical Centre Groningen.

BACKGROUND: Ten years ago, there was a difference of opinion about the suitability of ventilated patients with end-stage cardiac failure for heart transplantation (HTX). Although guidelines at that time qualified mechanical ventilation as a contraindication, we thought those patients could be candidates for HTX. In the same period a number of other patients received a donor heart in our centre. In this article we describe the clinical course and survival after these procedures. METHODS: We performed a retrospective study using our post HTX database. All patients undergoing transplants in our hospital were selected. Patients underwent echocardiography, scintigraphy (MUGA), ergo-spirometry (VO2 peak), blood tests and completed a quality of life questionnaire (SF-36). All tests were completed in the 1st quarter of 2006. RESULTS: Eight patients were identified; three were mechanically ventilated at the time of HTX. All eight patients were treated according to the standard protocol. Repeated surveillance cardiac biopsies were taken. One patient died 3.5 years after HTX due to an acute myocardial infarction. Seven patients, including the three patients on a ventilator at the time of the HTX, are alive, resulting in a survival rate of 88%. The current median survival time is 126 months (range 55 to 184 months). All patients are in good cardiac condition. The SF-36 domains of social functioning and mental health show high scores, the average score of general health and vitality is moderate. CONCLUSION: Survival of our eight transplanted patients after a median period of ten years was 88%, which is at least comparable with data from larger series. This finding suggests that HTX can be performed effectively and safely in a low volume centre. The finding that all three patients on a ventilator prior to HTX are alive is remarkable. It appears that mechanical ventilation is not always an absolute contraindication for HTX.

Influence of hemodilution of plasma proteins on erythrocyte aggregability: an in vivo study in patients undergoing cardiopulmonary bypass.

Erythrocyte aggregation is known to be affected by a number of factors including the concentration of various plasma proteins. This study was performed to examine the in vivo effect of hemodilution of plasma proteins on erythrocyte aggregation in patients undergoing cardiopulmonary bypass (CPB) surgery. Blood samples were taken before, during, and after operation from 40 coronary artery bypass grafting patients who were operated with CPB and concomitant hemodilution (CPB, n=20) and who without (nonCPB, n=20). Erythrocyte aggregation was determined with a LORCA aggregometer, during which all samples were standardized to a hematocrit level of 40%. Results showed that in the CPB patients the aggregation index (AI) dropped to 44% of its preoperative baseline level 5 minutes after the start of hemodilution (from 47.7+/-10.1 to 26.6+/-11.4, p<0.01). Meanwhile, plasma concentration of fibrinogen (Fb) dropped to 55%, haptoglobin to 85%, ceruloplasmin to 55%, and albumin to 67%. In the nonCPB patients, however, there was only a slight drop in AI and the concentrations of plasma proteins during the similar period of time. On postoperative day 1, AI was rebounded to 37.1+/-12.4 in CPB patients compared with 44.3+/-11.7 in nonCPB patients. At baseline, AI was correlated only with Fb. During CPB and hemodilution, AI was correlated not only with Fb but also with haptoglobin and ceruloplasmin. Postoperatively, significant correlationship was found between AI and Fb, CRP, haptoglobin, ceruloplasmin, as well as albumin. These results indicate that hemodilution of plasma proteins significantly reduces the aggregability of erythrocytes in patients undergoing CPB. Besides Fb, other plasma proteins also contribute to AI during the early postoperative period when patients are recovering from CPB surgery.

A 16-slice multidetector computed tomography protocol for evaluation of the gastroepiploic artery grafts in patients after coronary artery bypass surgery.

Arterial coronary bypass grafts [internal mammary arteries and gastroepiploic artery (GEA)] are in widespread use for coronary surgery. Since selective catheterisation of the GEA graft to monitor patency, is often unsuccessful, a non-invasive protocol to visualise the GEA-graft from origin to anastomosis is presented using 16-slice multidetector computed tomography (MDCT). Twenty-six male patients (mean age 58.1+/-6.7 years) with GEA grafts were scanned according to a protocol of an ECG-synchronised cardiac scan followed by a thoracoabdominal scan. To terminate the scan at the correct anatomical level, the lowest level of the GEA was coded based on the lumbar vertebrae level. Scores ranging from one (excellent) to four (bad) were assigned to evaluate visualisation quality of the grafts. GEA grafts were assessable in 62% of the thoracoabdominal scans and 69% of the cardiac scans. On average, the lowest part of the GEA corresponded with a level between L1 and L2, in two cases in the upper part of L3. Mean visualisation score in the thoracoabdominal scans and cardiac scans was good (respectively 1.4+/-0.6 and 1.4+/-1.0). Sixteen-slice MDCT is a promising alternative for catheterisation in evaluating patency of GEA grafts, using the presented protocol with thoracoabdominal scan including L3 for complete coverage of the GEA graft.

Augmentation of abdominal organ perfusion during cardiopulmonary bypass with a novel intra-aortic pulsatile catheter pump.

BACKGROUND: Current pulsatile pumps for cardiopulmonary bypass (CPB) are far from satisfactory because of the poor pulsatility. This study was undertaken to examine the efficiency of a novel pulsatile catheter pump on pulsatility and its effect on abdominal organ perfusion during CPB. METHODS: Twelve pigs weighing 89+/-11 kg were randomly divided into a pulsatile group (n=6) and a non-pulsatile group (n=6). All animals had a CPB for 120 min, aorta clamped for 60 min, temperature down to 32 degrees C, and a perfusion flow of 60 ml/kg/min. In the pulsatile group, a 21 Fr intra-aortic pulsatile catheter, which was connected to a 40 mL membrane pump, was placed in the descending aorta and activated by a balloon pump driver during the first 90 minutes of CPB until aortic declamping. Hemodynamics, organ blood flow, body metabolism, and blood trauma were studied during experiments. RESULTS: Compared with the non-pulsatile group during CPB, the pulsatile group had a higher systolic blood pressure (p<0.01), higher mean arterial pressure (p<0.05), and higher blood flow to the superior mesenteric artery (p<0.05). The hemodynamic energy, indicated by the energy equivalent pressure (EEP) was higher in the gastrointestinal tract and kidney in the pulsatile group (p<0.01, p<0.01). Abdominal organ perfusion status, as indicated by SvO 2 in the inferior vena cava, was higher in the pulsatile group (p<0.05) 30 min after cessation of CPB. Hemolysis indicated by release of free hemoglobin during CPB was similar in the two groups. CONCLUSION: Applying the pulsatile catheter pump in the descending aorta is effective in supplying the pulsatile flow to the abdominal organs and results in improved abdominal organ perfusion during the ischemic phase of CPB.

Endoventriculoplasty using autologous endocardium for anterior left ventricular aneurysms.

BACKGROUND: There is currently consensus that endoventriculoplasty is the treatment of choice for an anterior left ventricular aneurysm. We describe here a new technique of endoventriculoplasty using autologous endocardium for left ventricular anterior aneurysm. METHOD: From 1990 until 2003, 49 patients underwent endoventriculoplasty using autologous pericardium at the Thoraxcenter of the University Hospital of Groningen in the Netherlands (28 patients) and at the Department of Cardio Thoracic Surgery of the University Hospital of Pisa in Italy (21 patients). Mean logistic EuroSCORE and mean ejection fraction were 15.7 +/- 6.7 and 31 +/- 9 %, respectively. RESULTS: Overall 30-day mortality was 4.1 %. Causes of in-hospital mortality were low output syndrome (1 patient) and ventricular fibrillation (1 patient). Postoperative complications were myocardial infarct (4.1 %), low output syndrome (6.1 %), renal failure (4.1 %), neurological events (2.0 %), atrial fibrillation (14.3 %), ventricular fibrillation or tachycardia (6.1 %), ARDS (4.1 %), re-operation for bleeding (4.1 %), and major wound infection (2.0 %). CONCLUSION: Our analysis shows that endoventriculoplasty with autologous endocardium is a safe procedure and improves the outcome in high-risk patients with ventricular aneurysm.

Stridor and Horner's syndrome, weeks after attempted right subclavian vein cannulation.

A 23-year-old woman presented with renal failure resulting from polycystic kidney disease (PKD) aggravated by tubulo-interstitial nephritis. Emergency haemodialysis was planned, and cannulation of the right subclavian vein was attempted, but failed. During this procedure, inadvertent arterial puncture occurred. Transient mild ischaemia of the right arm, and a transient Horner's syndrome were noted. Seven weeks later she presented with severe stridor with impending respiratory failure necessitating emergency intubation; the right-sided Horner's syndrome had recurred. CT imaging showed a large pseudo-aneurysm of the brachiocephalic artery resulting in severe compression of the trachea. Using a prosthetic graft, the operation for the pseudo-aneurysm was successful; there were mild neurological sequelae. Although her family history was negative, autosomal dominant PKD should be considered, and we discuss the possible role of a pre-existing PKD-associated aneurysm.

The practicing physician's current perspective on therapeutic options in coronary artery disease.

Over the past decades the management of patients with stable as well as unstable manifestations of coronary artery disease has evolved in every aspect of routine clinical practice. Modern diagnostic modalities allow reliable and objective assessment of both the anatomical and functional consequences of the early as well as advanced stages of this disease, which remains one of the most important causes of morbidity and mortality worldwide. Pharmacological therapy now includes several classes of drugs with mortality benefits documented by randomised controlled trials. Surgical and percutaneous revascularisation techniques have shown rapid technical improvements and are now applicable in a wide range of clinical conditions. In this paper we will attempt to place the current status of the three therapeutic options for patients with coronary artery disease into perspective. It is important to realise that it is impossible to write a complete overview, a Pubmed search: 'PCI or drug therapy or surgery for coronary artery disease' results in 1,152,117 hits. Therefore, we have chosen the viewpoint of the practicing physician to synthesise this abundance of information in the context of modern clinical practice in a high volume cardiothoracic and cardiological practice.

Analysis of red blood cell aggregation in cardio-pulmonary bypass (CPB) surgery.

Not much is known about red cell aggregation during cardio-pulmonary bypass surgery (CPB). Blood samples from 19 patients undergoing CPB were anticoagulated with EDTA. Hematocrit was adjusted to 40%. A red blood cell aggregometer (LORCA) measured changes in light reflection from each blood sample after cessation of the rotation, and calculated an aggregation index (AI). Reflection measurements were stored. Because LORCA software failed for 87 of 171 samples, we developed new software, and applied it to the stored reflection measurements. This software failed only in 7 out of 171 cases and showed that all LORCA failures occurred for AI < 40%. The new calculations revealed that the aggregation index significantly decreased from 46.6 +/- 10.1 (mean +/- standard deviation) baseline to 22.8 +/- 8.3 at the end of CPB and recovered to 37.1 +/- 13.5 at day 1. It is concluded that the new software can be used to study decreased red cell aggregation during CPB.