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R Sutton

Publications and source records attributed to R Sutton.

At least 55 records · Page 3Linked to original sources
PubMed2002

Complications of pancreatic cancer resection.

Pancreatic cancer is a common cause of cancer death in the developed world. Currently, resection is the only chance of long-term survival. The post-operative mortality in nonspecialist centres often exceeds 20% but is around 6% or less in specialist centres. The overall complication rate even in specialist centres is 18-54%. An analysis of eleven large series of pancreatic resections shows an incidence of common complications of 10.4% for fistula, 9.9% for delayed gastric emptying, 4.8% for bleeding, 4.8% for wound infection and 3.8% for intra-abdominal abscess. The median hospital stay is 13-18 days in different series. The re-operation rate varies from 4 to 9% with a mortality rate of 23 to 67%. Major complications are a significant factor in post-operative mortality, especially if they require re-operation. The use of octreotide or somatostatin to prevent complications is supported by several multicentre, double-blind, randomized controlled trials. The best way to improve outcome is to concentrate pancreatic cancer care in regional specialist centres.

Anastomosis, Surgical↗
PubMed2001

The World Survey of Cardiac Pacing and Implantable Cardioverter Defibrillators: calendar year 1997--Europe.

The registry of the European Working Group on Cardiac Pacing (EWGCP) is based on the European Pacemaker Identification Card originally designed in July 1978. National registration centers collect the local data and send aggregated annual data to the EWGCP. For 1997, data were obtained from 2,887 hospitals in 20 European countries representing a population of 568 million. Across all participating countries, the median value for all implanted pacemakers was 378 per million population. For initial pacemaker implants, the median value was 290 per million population. Single chamber atrial pacing was important in Denmark, the Netherlands, Poland, Slovak Republic, Spain, and Sweden for the treatment of sick sinus syndrome. Dual chamber pacing accounted for < 50% of initial implants in only 5 of 14 countries for atrioventricular block, and in only 3 of 15 countries for sick sinus syndrome. In 7 of 15 countries, unipolar ventricular leads were used in > or = 50% of cases. In 6 of 14 countries, there was > 15% use of unipolar atrial leads. Nine of 13 countries frequently used atrial active-fixation leads. For the 1997 survey, ICD data were obtained from 16 countries. The total number of ICDs per million population was a median value of 14. Initial ICD implants per million population was 11. Only 3 of 16 countries implanted a total of 30 or more ICDs per million population. Pacing and ICD practices were dependent on the availability of medical and technical resources and influenced by economic constraints inherent in health care administration and insurance coverage patterns.

Aged↗
PubMed2001

Permanent pacemaker implantation via the femoral vein: an alternative in cases with contraindications to the pectoral approach.

BACKGROUND: This paper presents a consecutive series of permanent pacemakers (PPM) implanted via the femoral vein in patients with contraindications to pacing systems via the superior vena cava (SCV). The femoral vein approach is a less invasive and feasible alternative to epicardial lead placement. METHODS: Twenty-seven patients had femoral pacemakers inserted. Indications for femoral vein pacemaker insertion were: SVC/subclavian obstruction (12 patients, 44.4%), previous infection in SVC leads (four patients, 14.8%), mastectomy and/or radiotherapy to chest (four patients, 14.8%), multiple leads in SVC (two patients, 7.4%), recurrent erosion (two patients, 7.4%), abnormal anatomy (one patient, 3.7%), painful pacemaker pocket (one patient, 3.7%) and burns (one patient, 3.7%). Fifty-one leads, 25 atrial and 26 ventricular, were inserted. The majority of leads were active fixations (96% of atrial leads and 85% ventricular leads). RESULTS: During a mean follow-up of 36.5 months (range 0.9-116.5), six additional unplanned procedures were performed in four patients. Atrial lead displacement occurred in five leads (20%). There were no ventricular lead displacements. In two patients, box revision for pre-erosion was required. One patient had persistent pain at the site of abdominal pacemaker generator. Infection, thromboembolic events, thromophlebitis, evidence of lower limb venous occlusion and lead fracture did not occur. CONCLUSION: Femoral vein PPM are a simple and feasible alternative in patients in whom the SVC approach is contraindicated.

Adult↗
PubMed2001

The vasovagal Syncope and pacing (Synpace) trial: rationale and study design.

BACKGROUND: Though vasovagal syncope probably does not directly cause death, it is often associated with severe trauma and, when recurrent, significantly impairs the patient's quality of life. While drug therapy for vasovagal syncope is still controversial, recently two randomized studies revealed the efficacy of dual-chamber pacemaker implantation in decreasing recurrences in very symptomatic patients. However, since both studies were not placebo-controlled, the benefits observed might have been due to the placebo effect of the pacemaker. AIM OF THE STUDY: The aim of the vasovagal Syncope and pacing (Synpace) trial, a multicentre, prospective, randomized, double-blind, placebo-controlled trial, is to ascertain whether, in patients suffering from recurrent vasovagal syncope, the implantation of a dual-chamber pacemaker with rate drop response algorithm programmed to ON, will reduce syncope relapses compared with the implantation of a pacemaker programmed to OFF. Moreover, in order to evaluate the role of the haemodynamic response during tilt-induced syncope in identifying those patients who will benefit most from pacemaker implantation, enrolled patients will be divided into two groups on the basis of their haemodynamic behaviour during tilt-induced syncope: group 1, asystolic response (development of asystole >3 s), and group 2, mixed response (development of bradycardia <60 bpm, without asystole >3 s). The head-up tilt testing protocol will consist of 20 min at 60 degrees without drug potentiation, followed by 15 min at the same inclination after 400 microg of sublingual nitroglycerin. Results from the two groups will be analysed both separately and globally. The primary clinical endpoint of the study will be syncope. INCLUSION AND EXCLUSION CRITERIA: To be enrolled, patients will have to meet the following criteria: at least six syncopal episodes in the patient's lifetime; positive head-up tilt testing with asystolic or mixed response; at least one syncope recurrence following a positive head-up tilt test. The following constitute exclusion criteria: non-vasovagal syncope; other indications for pacing. SAMPLE SIZE: We hypothesize a risk of syncope recurrence of 70% after one year, and we estimate that--owing to the placebo effect alone--pacemaker will produce a 20% decrease in risk, which corresponds to a 50% risk of recurrence after one year, in those patients randomized to 'pacemaker OFF'. We calculate conservatively a risk decrease of 60% in patients with 'pacemaker ON'. This implies a 10% incidence of syncope recurrence after one year, vs 50% in patients with 'pacemaker OFF'. Fifty patients will need to be enrolled in the study: 25 patients for each group.

Databases as Topic↗
PubMed2001

Atrial and ventricular electromechanical function in 1-ventricle hearts: influence of atrial flutter and Fontan procedure.

OBJECTIVE: Echocardiography was used to study electromechanical atrial and ventricular function in adult patients with a 1-ventricle heart who were in sinus rhythm to better understand the recurrence of atrial flutter in these conditions. Patients who had recent atrial flutter, with and without the Fontan procedure, were compared with those who had no arrhythmia. METHODS: This was a prospective study that used M-mode and 2-dimensional Doppler echocardiography and electrocardiography. Conventional measurements were used to evaluate ventricular long-axis function. Basic data were drawn from case notes. The setting was a designated quaternary service for grown-up congenital heart patients (GUCH) in a tertiary referral center for cardiology and cardiac surgery. From January 1997 to February 1998, 26 consecutive adult patients (aged >16 years) with a heart with one functioning ventricle and a history of atrial flutter were studied: group 1, with non-Fontan palliative surgery or no surgery (10 patients), and group 2, with Fontan-type repair (16 patients). Also studied were 20 patients with a 1-ventricle heart but no history of atrial flutter. These 20 patients were divided into 2 groups: control 1, which comprised 14 patients with previous shunts or no surgery, and control 2, which consisted of 6 patients with Fontan repair. RESULTS: P-wave duration on the electrocardiogram was similar in the 4 patient groups, but the amplitude was reduced in group 2 and control 2 (patients with Fontan surgery) (P <.016). Bifid P wave was seen in 5 (50%) of 10 patients in group 1 and in 6 (43%) of 14 patients in control 1, but it was not seen in patients with Fontan (P <.01). Ventricular systolic and diastolic dimensions and fractional shortening were not different between patients and controls. Right atrial transverse dimensions were greater in group 2 patients compared with those in controls. Significant atrioventricular valve regurgitation was seen in 9 of 10 group 1 patients but in none of the others. Right-sided total long-axis excursion and atrial A-wave amplitude were depressed in group 2 patients compared with the values in the others. The onset of right atrial shortening was delayed by 50 ms in group 2 compared with control 2, whereas the left atrial shortening was delayed by 30 ms in group 1 compared with control 1. This particular disturbance remained 6 months after cardioversion. CONCLUSION: In 1-ventricle hearts, significant atrioventricular valve regurgitation is commonly associated with atrial flutter in patients who did not undergo the Fontan procedure, and with electromechanical disturbances in those who did. Recognition of disturbances in ventricular long-axis function may thus assist in the identification of patients with a 1-ventricle heart who are prone to atrial flutter.

Adolescent↗
PubMed2001

Influence of resection margins on survival for patients with pancreatic cancer treated by adjuvant chemoradiation and/or chemotherapy in the ESPAC-1 randomized controlled trial.

OBJECTIVE: To assess the influence of resection margins on survival for patients with resected pancreatic cancer treated within the context of the adjuvant European Study Group for Pancreatic Cancer-1 (ESPAC-1) study. SUMMARY BACKGROUND DATA: Pancreatic cancer is associated with a poor long-term survival rate of only 10% to 15% after resection. Patients with positive microscopic resection margins (R1) have a worse survival, but it is not known how they fare in adjuvant studies. METHODS: ESPAC-1, the largest randomized adjuvant study of resectable pancreatic cancer ever performed, set out to look at the roles of chemoradiation and chemotherapy. Randomization was stratified prospectively by resection margin status. RESULTS: Of 541 patients with a median follow-up of 10 months, 101 (19%) had R1 resections. Resection margin status was confirmed as an influential prognostic factor, with a median survival of 10.9 months for R1 versus 16.9 months months for patients with R0 margins. Resection margin status remained an independent factor in a Cox proportional hazards model only in the absence of tumor grade and nodal status. There was a survival benefit for chemotherapy but not chemoradiation, irrespective of R0/R1 status. The median survival was 19.7 months with chemotherapy versus 14.0 months without. For patients with R0 margins, chemotherapy produced longer survival compared with to no chemotherapy. This difference was less apparent for the smaller subgroup of R1 patients, but there was no significant heterogeneity between the R0 and R1 groups. CONCLUSIONS: Resection margin-positive pancreatic tumors represent a biologically more aggressive cancer; these patients benefit from resection and adjuvant chemotherapy but not chemoradiation. The magnitude of benefit for chemotherapy treatment is reduced for patients with R1 margins versus those with R0 margins. Patients with R1 tumors should be included in future trials of adjuvant treatments and randomization and analysis should be stratified by this significant prognostic factor.

Adenocarcinoma↗
PubMed2001

Notch1IC partially replaces EBNA2 function in B cells immortalized by Epstein-Barr virus.

Immortalization of B cells by Epstein-Barr virus (EBV) depends on the virally encoded EBNA2 protein. Although not related by sequence, the cellular Notch protein and EBNA2 share several biochemical and functional properties, such as interaction with CBF1 and the ability to activate transcription of a number of cellular and viral genes. Whether these similarities are coincidental or exemplify EBNA2 mimicry of evolutionarily conserved cellular signaling pathways is unclear. We therefore investigated whether activated forms of Notch could substitute for EBNA2 in maintaining the immortalized phenotype of EBV-infected B cells. To address this question, we devised a transcomplementation system using EREB2.5 cells. EREB2.5 cells are immortalized by EBV expressing a conditional estrogen receptor EBNA2 fusion protein (EREBNA2), and cellular proliferation is dependent on the availability of estrogen. Withdrawal of estrogen results in inactivation of EREBNA2, leading to growth arrest and eventually to cell death. Transduction of EREB2.5 cells with a lentiviral vector expressing wild-type EBNA2 rescued EREB2.5 cells from the growth-inhibitory effects of estrogen deprivation, in contrast to transduction with the lentivirus vector alone. EREB2.5 cells were also rescued by enforced expression of human Notch1IC after estrogen starvation, but this effect was restricted to cells expressing high levels of the transcription factor. Compared to wild-type EBNA2-expressing EREB2.5 cells, the Notch-expressing cells expanded more slowly after estrogen starvation, and once established, they continued to display a lower proliferation rate. Analysis of viral and cellular gene expression from transduced EREB2.5 cells after estrogen withdrawal indicated that both wild-type EBNA2- and Notch1IC-positive cells expressed c-Myc at levels similar to those found in parental EREB2.5 cells. However, the latter cells expressed LMP-1 far less efficiently than cells transduced with the wild-type EBNA2 gene. Cells rescued by either wild-type EBNA2 or Notch1IC expressed surface CD21 and CD23 proteins, but not CD10, indicating that induction of relevant type III latency markers was maintained. The data imply that both Notch and EBNA2 activate an important subset of cellular genes associated with type III latency and B-cell growth, while EBNA2 more efficiently induces important viral genes, such as LMP-1. Thus, exploitation of conserved Notch-related signaling pathways may represent a key mechanism by which EBNA2 contributes to EBV-induced cell immortalization.

B-Lymphocytes↗
PubMed2001

Molecular diagnosis of early pancreatic ductal adenocarcinoma in high-risk patients.

The prevalence of pancreatic cancer in the general population is too low--even in high-prevalence areas such as Northern Europe and North America (8-12 per 10(5) population)--relative to the diagnostic accuracy of present detection methods to permit primary screening in the asymptomatic adult population. The recognition that the lifetime risk of developing pancreatic cancer for patients with hereditary pancreatitis (HP) is extremely high (20% by the age of 60 years and 40% by the age of 70 years) poses considerable challenges and opportunities for secondary screening in those patients without any clinical features of pancreatic cancer. Even for secondary screening, the detection of cancer at a biological stage that would be amenable to cure by surgery (total pancreatectomy) still requires diagnostic modalities with a very high sensitivity and specificity. Conventional radiological imaging methods such as endoluminal ultrasound and endoscopic retrograde pancreatography, which have proved to be valuable in the early detection of early neoplastic lesions in patients with familial pancreatic cancer, may well be applicable to patients with HP but only in those without gross morphological features of chronic pancreatitis (other than parenchymal atrophy). Unfortunately, most cases of HP also have associated gross features of chronic pancreatitis that are likely to seriously undermine the diagnostic value of these conventional imaging modalities. Pre-malignant molecular changes can be detected in the pancreatic juice of patients. Thus, the application of molecular screening in patients with HP is potentially the most powerful method of detection of early pancreatic cancer. Although mutant (mt) K-ras can be detected in the pancreatic juice of most patients with pancreatic cancer, it is also present in patients with non-inherited chronic pancreatitis who do not progress to pancreatic cancer (at least in the short to medium term), as well as increasingly in the older population without pancreatic disease. Nevertheless, the presence of mt-K-ras may identify a genuinely higher-risk group, enabling additional diagnostic imaging and molecular resources to be focussed on such a group. What is clear is that prospective multi-centre studies, such as that being pursued by the European Registry of Hereditary Pancreatitis and Familial Pancreatic Cancer (EUROPAC), are essential for the development of an effective secondary screening programme for these patients.

Biomarkers, Tumor↗
PubMed2001

Management of necrotizing pancreatitis.

Infection complicating pancreatic necrosis leads to persisting sepsis, multiple organ dysfunction syndrome and accounts for about half the deaths that occur following acute pancreatitis. Severe cases due to gallstones require urgent endoscopic sphincterotomy. Patients with pancreatic necrosis should be followed with serial contrast enhanced computed tomography (CE-CT) and if infection is suspected fine needle aspiration of the necrotic area for bacteriology (FNAB) should be undertaken. Treatment of sterile necrosis should initially be nonoperative. In the presence of infection necrosectomy is indicated. Although traditionally this has been by open surgery, minimally invasive procedures are a promising new alternative. There are many unresolved issues in the management of pancreatic necrosis. These include, the use of antibiotic prophylaxis, the precise indications for and frequency of repeat CE-CT and FNAB, and the role of enteral feeding.

Humans↗
PubMed2001

Adjuvant therapy in pancreatic cancer.

The outlook for patients with pancreatic cancer has been grim. There have been major advances in the surgical treatment of pancreatic cancer, leading to a dramatic reduction in post-operative mortality from the development of high volume specialized centres. This stimulated the study of adjuvant and neoadjuvant treatments in pancreatic cancer including chemoradiotherapy and chemotherapy. Initial protocols have been based on the original but rather small GITSG study first reported in 1985. There have been two large European trials totalling over 600 patients (EORTC and ESPAC-1) that do not support the use of chemoradiation as adjuvant therapy. A second major finding from the ESPAC-1 trial (541 patients randomized) was some but not conclusive evidence for a survival benefit associated with chemotherapy. A third major finding from the ESPAC-1 trial was that the quality of life was not affected by the use of adjuvant treatments compared to surgery alone. The ESPAC-3 trial aims to assess the definitive use of adjuvant chemotherapy in a randomized controlled trial of 990 patients.

Antineoplastic Agents↗
PubMed2001

Acute gallstone pancreatitis in childhood.

Acute pancreatitis is rarely considered in the diagnosis of paediatric abdominal pain and can be misdiagnosed. Gallstones are uncommon in children and are a rare cause of pancreatitis. Trauma, infections and idiopathic causes are the commonest aetiological factors. Three cases of gallstone-induced acute pancreatitis with jaundice in children are reported which resolved with conservative treatment. The gallstones were managed by laparoscopic cholecystectomy with or without endoscopic retrograde cholangiopancreatography (ERCP). The three children had presented previously to a doctor with symptoms of gallstone disease but the diagnosis was missed. It is concluded that acute pancreatitis should be considered in children presenting as an emergency with abdominal pain. Children with recurrent attacks of upper abdominal pain should be investigated for gallstone disease so that the diagnosis is made before the development of potentially serious complications such as acute pancreatitis and jaundice.

Acute Disease↗
PubMed2000

Calcium-dependent enzyme activation and vacuole formation in the apical granular region of pancreatic acinar cells.

The pancreatic acinar cell produces powerful digestive enzymes packaged in zymogen granules in the apical pole. Ca(2+) signals elicited by acetylcholine or cholecystokinin (CCK) initiate enzyme secretion by exocytosis through the apical membrane. Intracellular enzyme activation is normally kept to a minimum, but in the often-fatal human disease acute pancreatitis, autodigestion occurs. How the enzymes become inappropriately activated is unknown. We monitored the cytosolic Ca(2+) concentration ([Ca(2+)](i)), intracellular trypsin activation, and its localization in isolated living cells with specific fluorescent probes and studied intracellular vacuole formation by electron microscopy as well as quantitative image analysis (light microscopy). A physiological CCK level (10 pM) eliciting regular Ca(2+) spiking did not evoke intracellular trypsin activation or vacuole formation. However, stimulation with 10 nM CCK, evoking a sustained rise in [Ca(2+)](i), induced pronounced trypsin activation and extensive vacuole formation, both localized in the apical pole. Both processes were abolished by preventing abnormal [Ca(2+)](i) elevation, either by preincubation with the specific Ca(2+) chelator 1, 2-bis(O-aminophenoxy)ethane-N,N-N',N'-tetraacetic acid (BAPTA) or by removal of external Ca(2+). CCK hyperstimulation evokes intracellular trypsin activation and vacuole formation in the apical granular pole. Both of these processes are mediated by an abnormal sustained rise in [Ca(2+)](i).

Animals↗
PubMed2000

Dual-chamber pacing in the treatment of neurally mediated tilt-positive cardioinhibitory syncope : pacemaker versus no therapy: a multicenter randomized study. The Vasovagal Syncope International Study (VASIS) Investigators.

BACKGROUND-This study was performed to compare implantation of a DDI pacemaker with rate hysteresis with no implant in respect to syncopal recurrences in patients with severe cardioinhibitory tilt-positive neurally mediated syncope. METHODS AND RESULTS-Forty-two patients from 18 European centers were randomized to receive a DDI pacemaker programmed to 80 bpm with hysteresis of 45 bpm (19 patients) or no pacemaker (23 patients). Inclusion criteria were >/=3 syncopes over the last 2 years and a positive cardioinhibitory (Vasovagal Syncope International Study types 2A and 2B) response to tilt testing. The median number of previous syncopal episodes was 6; asystolic response to tilt testing was present in 36 patients (86%) (mean asystole, 13.9+/-10.2 seconds). All patients were followed up for a minimum of 1.0 years and a maximum of 6.7 years (mean, 3.7+/-2.2). One patient (5%) in the pacemaker arm experienced recurrence of syncope compared with 14 patients (61%) in the no-pacemaker arm (P=0.0006). In the no-pacemaker arm, the median time to first syncopal recurrence was 5 months, with a rate of 0.44 per year. On repeated tilt testing performed within 15 days after enrollment, positive responses were observed in 59% of patients with pacemakers and in 61% of patients without pacemakers (P=NS). CONCLUSIONS-In a limited, select group of patients with tilt-positive cardioinhibitory syncope, DDI pacing with hysteresis reduced the likelihood of syncope. The benefit of the therapy was maintained over the long term. Even in untreated patients, the syncopal recurrence burden was low. A negative result of tilt testing was not a useful means to evaluate therapy efficacy.

Aged↗