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Recently, the first human medicine containing a genetically modified organism (GMO medicine) was authorized for use in the European market. Just as any medicinal product, the market authorization for a GMO medicine contains a precise description of the therapeutic use for which the medicinal product is intended. Within this use, the application of the GMO medicine is permitted, without the need for the institution to obtain a specific permit. In practice, however, medicinal products are also frequently prescribed for treatment outside the registered therapeutic use, a practice that is referred to as "off-label use." While off-label use of conventional medicines is permitted and has been very useful, the off-label use of GMO medicines is not covered in the European Union (EU) legislation or guidelines and falls under each member state's national environmental legislation. This implies that in the Netherlands and most other EU member states, an environmental permit will be required for any institution that uses the GMO medicine outside the registered application(s). In the Netherlands, this permit is identical to the permits required for the execution of clinical trials involving nonregistered GMOs. The application procedure for such permit is time-consuming. This process can therefore limit the therapeutic options for medical professionals. As a consequence, desired treatment regimens could be withheld for certain patient (groups). To make future off-label use of GMO medicines permissible in a way that is acceptable for all stakeholders, regulators should adopt a proactive attitude and formulate transparent legislative procedures for this. Only then the field can maintain the public acceptance of GMO medicines, while maintaining the freedom to operate of medical professionals.

Background: Definitive (chemo)radiotherapy is employed in esophageal cancer patients as an alternative for patients considered medically unfit for surgery or having unresectable tumors. We evaluated a population-based cohort to improve the selection for intensified nonsurgical strategies and to identify prognostic factors., Methods: Patients who had squamous cell carcinoma (SCC) or adenocarcinoma (AC) were treated in four referral centers in the north-east Netherlands with definitive chemoradiotherapy (dCRT) or radiotherapy (dRT) between 1996 and 2008., Results: Of the 287 included patients, 110 were treated with dCRT and 177 with dRT. Median overall survival (OS) was 11 months (95 % confidence interval: 10-12 months), with OS of 22 and 8 % and disease-free survival (DFS) of 16 and 5 % at 2 and 5 years, respectively. DFS at 2 and 5 years was 24 and 9 % for SCC versus 10 and 2 % for AC patients (P = 0.006). OS after 2 and 5 years was 29 and 14 % for SCC patients versus 17 and 3 % for AC patients (P = 0.044). On multivariate Cox regression, SCC was an independent prognostic factor for DFS [P = 0.020, hazard ratio (HR) = 0.71] and OS (P = 0.047, HR = 0.76). On matched cohort analysis, DFS was higher in the dCRT group compared with dRT patients (P = 0.016). The locoregional failure rate was lower in the dCRT group and in SCC patients (P = 0.001 and 0.046)., Conclusions: Long-term results and the local control rate in SCC patients were better after definitive (chemo)radiotherapy compared with in AC patients. SCC was an independent prognostic factor for survival. Definitive chemoradiotherapy leads to improved local control rate and DFS.

Background: Survival differences in stomach cancer are depended on patient, tumour and treatment factors. Some populations are more prone to develop stomach cancer, such as people with low socioeconomic status (SES). The aim of this population based study was to assess whether differences in socioeconomic status (SES) alone, after adjusting for confounding factors, also influence survival., Methods: From 1989 to 2007 all patients with stomach cancer were selected from the cancer registry of the Comprehensive Cancer Centre North-East. Postal code at diagnosis was used to determine SES, dividing patients in three groups; low, intermediate and high SES. Associations between age, localization, grade, stage, and treatment were determined using Chi-square analysis. Relative survival analysis was used to estimate relative excess risk (RER) of dying according to SES., Results: In low SES neighbourhoods diagnosis was established at older age. More distal tumours were detected in patients with low SES, whereas pathology showed more poorly differentiated tumours in patients with high SES. Overall, more resections were performed in, and more chemotherapy was administrated to patients in high SES neighbourhoods. After adjusting for confounding factors, the risk of dying was lower for patients with high SES (RER 0.89, 95% Confidence Interval 0.81-0.98) compared to patients with low SES., Conclusion: SES proved to be an independent prognostic factor for survival in patients with stomach cancer., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: Isolated groups, such as first generation non-Western immigrants, are at risk for suboptimal utilisation of the health care system resulting in a worse outcome., Methods: From 1989 to 2007, all patients with stomach cancer were selected from the Comprehensive Cancer Centre North-East cancer registry. Associations between country of birth and patient, tumour and treatment characteristics were determined using χ(2) analysis. Relative survival analysis was used to estimate relative excess risk of dying according to country of birth (non-Western vs Western)., Results: After adjusting for confounding factors (patient, tumour and treatment related), the risk of dying was lower for first generation non-Western immigrants (relative excess risk 0.55, 95% confidence interval 0.43-0.70) compared with Western patients., Conclusion: Although the better survival of first generation non-Western immigrants with stomach cancer remains unexplained, it argues against accessibility problems within the Dutch health care system.

Background: Surgical resection is an important factor in the curative treatment of gastric cancer. However a variety of aspects of surgical treatment that potentially influence outcome are still not well defined. This study aims to assess the influence of hospital type, referral pattern and proximal or distal location of the tumour on the ultimate survival., Methods: From January 1994 to January 2007, a total of 5245 patients were diagnosed with gastric adenocarcinoma in the region of the Comprehensive Cancer Centre North-East Netherlands. Hospitals in this region were categorized into three types: teaching university (TU), teaching non-university (TNU), and non-teaching hospitals (NT). The influence of hospital type, referral for surgery and location of the tumour on the relative survival of operated patients was studied., Results: Of the 5245 patients, 2334 patients underwent surgery. For operated patients, the 5-year relative survival was 42.5% for the TU versus 34.0% and 35.5% for respectively TNU and NT hospitals (p = 0.064), with no difference (p = 0.38) in relative survival (25.6-31.9%) in the proximal tumours. A significant difference was found between the hospitals in the 5-year relative survival in the distal tumours; 59.7% in the TU versus 36.4% in the TNU and 36% in the NT (p = 0.03 univariate), however this was not confirmed in the multivariate analysis (p = 0.184). High referral centres did not perform better as far as survival is concerned than low referral hospitals. In conclusion the hospital type in our region did not significantly influence outcome of surgery for gastric cancer., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Extensive research is ongoing worldwide on the clinical utility of gene therapy, particularly for the treatment of cancer and genetic disorders. Two gene therapy products have already been approved recently in China. Clinical experience with gene therapy has also been accumulating in the Netherlands: over 200 Dutch patients have now been treated in clinical trials. Published results indicate that gene therapy is generally safe. Gene therapy appears to be effective for some genetic disorders, such as severe combined immune deficiency and haemophilia B. The efficacy of gene therapy, particularly in the treatment of cancer, appears to be limited up till now.

In a prospective randomized trial, 40 stage IV breast cancer patients undergoing intermediate high-dose chemotherapy (cyclophosphamide, 5-fluorouracil plus epirubicin or methotrexate), received either recombinant human G-CSF (rhG-CSF, group I) or ciprofloxacin and amphotericin B (CAB, group II) for prevention of febrile leucopenia (FL). In group I, seven of 18 patients developed FL (after 10/108 courses); in group II, seven of 22 patients (7/98 courses) (P = NS). Median hospitalization duration and costs were not different. RhG-CSF was 6.6 times more expensive per course than CAB. In conclusion, prophylactic CAB has similar efficacy to rhG-CSF in this setting, and is more cost-effective.

Dengue haemorrhagic fever in two female tourists to Thailand (1990) and Indonesia (1989) respectively, is reported for the first time in the Netherlands. The main symptoms directly after return were high fever, haemorrhagic exanthema, thrombocytopenia and in one patient signs of haemoconcentration. Initially both patients were treated with antibiotics. They recovered after intravenous fluid therapy; one of them received a thrombocyte transfusion. Increasing travel to Asia and South America will result in more tourists returning with this potentially serious arboviral disease (dengue haemorrhagic shock).