Two-year follow-up after catheter-based radiotherapy to inhibit coronary restenosis

BACKGROUND: Although early trials indicate the treatment of restenosis with radiation therapy is safe and effective, the long-term impact of this new technology has been questioned. The possibility of late untoward consequences, such as aneurysm formation, perforation, and accelerated vascular disease, is of significant concern. Furthermore, it is not known whether the beneficial effects of radiation therapy will be durable or whether radiation will only delay restenosis. METHODS AND RESULTS: A double-blind, randomized trial was undertaken to compare 192Ir with placebo sources in patients with previous restenosis after coronary angioplasty. Patients were randomly assigned to receive a 0.76-mm (0. 03-in) ribbon containing sealed sources of either 192Ir or placebo. All patients underwent repeat coronary angiography at 6 months. All living patients were contacted 24 months after their index study procedure. Patients were assessed with respect to the need for target-lesion revascularization or nontarget-lesion revascularization, occurrence of myocardial infarction, or death. Over a 9-month period, 55 patients were enrolled; 26 were randomized to 192Ir and 29 to placebo. Follow-up was obtained in 100% of living patients at a minimum of 24 months. Target-lesion revascularization was significantly lower in the 192Ir group (15.4% versus 44.8%; P<0. 01). Nontarget-lesion revascularization was similar in 192Ir and placebo patients (19.2% versus 20.7%; P=NS). There were 2 deaths in each group. The composite end point of death, myocardial infarction, or target-lesion revascularization was significantly lower in 192Ir-treated versus placebo-treated patients (23.1% versus 51.7%; P=0.03). No patient in the 192Ir group sustained a target-lesion revascularization later than 10 months. CONCLUSIONS: At 2-year clinical follow-up, treatment with 192Ir demonstrates significant clinical benefit. Although further follow-up (including late angiography) will be necessary, no clinical events have occurred to date in the 192Ir group to suggest major untoward effects of vascular radiotherapy. At the intermediate follow-up time point, vascular radiotherapy continues to be a promising new treatment for restenosis.     

The Current Role of Staging Laparoscopy in Oesophagogastric Cancer

Introduction

Oesophagogastric cancers are known to spread rapidly to locoregional lymph nodes and by transcoelomic spread to the peritoneal cavity. Staging laparoscopy combined with peritoneal cytology can detect advanced disease that may not be apparent on other staging investigations. The aim of this study was to determine the current value of staging laparoscopy and peritoneal cytology in light of the ubiquitous use of computed tomography in all oesophagogastric cancers and the addition of positron emission tomography in oesophageal cancer.

Methods

All patients undergoing staging laparoscopy for distal oesophageal or gastric cancer between March 2007 and August 2013 were identified from a prospectively maintained database. Demographic details, preoperative staging, staging laparoscopy findings, cytology and histopathology results were analysed.

Results

A total of 317 patients were identified: 159 (50.1%) had gastric adenocarcinoma, 136 (43.0%) oesophageal adenocarcinoma and 22 (6.9%) oesophageal squamous carcinoma. Staging laparoscopy revealed macroscopic metastases in 36 patients (22.6%) with gastric adenocarcinoma and 16 patients (11.8%) with oesophageal adenocarcinoma. Positive peritoneal cytology in the absence of macroscopic peritoneal metastases was identified in a further five patients with gastric adenocarcinoma and six patients with oesophageal adenocarcinoma. There was no significant difference in survival between patients with macroscopic peritoneal disease and those with positive peritoneal cytology (p=0.219).

Conclusions

Staging laparoscopy and peritoneal cytology should be performed routinely in the staging of distal oesophageal and gastric cancers where other investigations indicate resectability. Currently, in our opinion, patients with positive peritoneal cytology should not be treated with curative intent.     

Recombinant adeno-associated virus-mediated gene transfer into hematopoietic progenitor cells [published erratum appears in Blood 1995 Feb 1;85(3):862]

Recombinant adeno-associated viruses (rAAV) containing only the inverted terminal repeats (ITR) from the wild-type virus are capable of stable integration into the host cell genome, and expression of inserted genes in cultured cells. We have now defined the ability of rAAV to introduce genes into primary hematopoietic progenitors. A vector was constructed containing the coding sequences for beta- galactosidase (beta-gal), including a nuclear localization signal, under the control of a strong viral promotor. Infectious vector particles were prepared by cotransfection of the vector plasmid with a second plasmid that contained the coding sequences for AAV proteins into adenovirus-infected human embryonic kidney cells. These vector preparations transferred and expressed the beta-gal gene in human K562 erythroleukemia and Detroit 6 cells. Positive immunoselection yielded a population of enriched CD34+ cells that were transduced with the rAAV beta-gal vector. Nuclear localized enzyme expression was documented in 60% to 70% of infected cells. Progenitor-derived colonies that developed after 2 weeks in clonogenic cultures were shown to have viral- associated DNA at an estimated copy number of 1 to 2 per cell using a semiquantitative polymerase chain reaction (PCR) method. Integration of AAV into hematopoietic progenitors was documented using wild-type virus, as its genome may integrate at a preferred site on chromosome 19. Our data suggest that rAAV will transfer and express genes in primitive hematopoietic progenitors with high frequency, and support the development of this vector system for therapeutic gene transfer.     

Interfacing the ICU with the general practitioner

For many reasons it is crucial that treating intensivists have (regular) contact with general practitioners (GPs). Information about the premorbid condition of the patient, their will and wishes, is of importance to be able to set appropriate treatment goals. The GP is the doctor who is responsible for the patient once discharged from the hospital. Additionally, the GP can play an important early role in the support of relatives, provided the GP is timely informed. This kind of communication should be organized in a structured way within the intensive care unit department.     

Clinical review: Treatment of new-onset atrial fibrillation in medical intensive care patients: a clinical framework

Atrial fibrillation occurs frequently in medical intensive care unit patients. Most intensivists tend to treat this rhythm disorder because they believe it is detrimental. Whether atrial fibrillation contributes to morbidity and/or mortality and whether atrial fibrillation is an epiphenomenon of severe disease, however, are not clear. As a consequence, it is unknown whether treatment of the arrhythmia affects the outcome. Furthermore, if treatment is deemed necessary, it is not known what the best treatment is. We developed a treatment protocol by searching for the best evidence. Because studies in medical intensive care unit patients are scarce, the evidence comes mainly from extrapolation of data derived from other patient groups. We propose a treatment strategy with magnesium infusion followed by amiodarone in case of failure. Although this strategy seems to be effective in both rhythm control and rate control, the mortality remained high. A randomised controlled trial in medical intensive care unit patients with placebo treatment in the control arm is therefore still defendable.