Gastrointestinal lymphomas--the Dutch experience.
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Adolescent↗
Biomedical subjects
B G Taal
Publications and source records attributed to B G Taal.
Improved effect of 131I-MIBG treatment by predosing with non-radiolabeled MIBG in carcinoid patients, and studies in xenografted mice.
BACKGROUND: 131I-meta-iodobenzylguanidine (MIBG) has been used with success for the palliation of metastatic carcinoid. To qualify more patients for this treatment, we evaluated the effect of predosing with non-radiolabeled MIBG on 131I-MIBG tumour targeting in carcinoid patients and in mice with BON human carcinoid xenografts. PATIENTS AND METHODS: Ten carcinoid patients with a faint tumour imaging on a diagnostic 131I-MIBG scan (1 mCi = 37 MBq, 5 mg MIBG) received non-radiolabeled MIBG prior to a second scintigraphy. In case of improved tumour targeting patients were treated with 200 mCi (7.4 GBq) 131I-MIBG following a pharmacological predose of 20-40 mg/m2 MIBG. RESULTS: In six patients. highly increased 'tumour/non-tumour' ratios were seen due to reduced levels in normal tissues and increased tumour accumulation. The combined treatment applied in five patients, considerably improved symptoms in all (duration 6-12 months), accompanied by biochemical response in three. In BON carcinoid xenografted mice, MIBG was injected intraperitoneally followed by intravenous 125I-MIBG with similar findings: increased 'tumour/non-tumour' radioactivity ratios by 1.5-3-fold. CONCLUSION: Predosing with non-radiolabeled MIBG resulted in improved 131I-MIBG tumour targeting, prolonged palliation and encouragingly often biochemical responses in carcinoid.
3-Iodobenzylguanidine↗
Enhancement of 131I-MIBG uptake in carcinoid tumours by administration of unlabelled MIBG.
Iodine-131 metaiodobenzylguanidine (131I-MIBG) has been used with success for the palliation of symptomatic, metastatic carcinoid tumours. However, only 70% of cases are MIBG-avid and tumour uptake is not always sufficient for therapy. At The Netherlands Cancer Institute 34 carcinoid patients with no or insufficient uptake were treated with escalating doses of unlabelled ('cold') MIBG. No objective remissions were recorded, but a palliative effect (i.e. subjective disappearance of symptoms and/or reduction of medication by more than 50%) was observed in 60% of cases (mean duration 4.5 months). In 24 of the patients undergoing therapy with 'cold' MIBG, total body scintigraphy using 37 MBq 131I-MIBG was performed before and after infusion of 'cold' MIBG. The biodistribution of 131I-MIBG and its tumour to non-tumour ratios were compared. After 'cold' MIBG the 131I-MIBG uptake in the salivary glands was suppressed in all patients, myocardial uptake in 21, and uptake in normal liver tissue in 14. Pulmonary uptake was increased in 13 patients. More importantly, the tumour to non-tumour (T/NT) ratios improved in 17 of the 24 cases (by 7.8-111.4% at 24 h). Of the initial six patients demonstrating a significant increase in the T/NT ratio, five have subsequently received combined treatment of 7.4 GBq 131I-MIBG following the administration of 'cold' MIBG (both by 4 h intravenous infusion), resulting in a good palliative response in four of them. These patients had previously been excluded from therapy with 131I-MIBG only. It is concluded that the administration of unlabelled MIBG may not only provide palliation to patients with carcinoid tumours, but may also alter the biodistribution of MIBG, enabling 131I-MIBG therapy to be used in cases not qualifying for this treatment due to insufficient tumour uptake.
3-Iodobenzylguanidine↗
Thymidylate synthase expression in patients with colorectal carcinoma using a polyclonal thymidylate synthase antibody in comparison to the TS 106 monoclonal antibody.
Colorectal cancer is one of the most common human cancers, for which 5-fluorouracil (5FU) is usually part of the treatment. Thymidylate synthase (TS), the target enzyme for 5FU, can be predictive for the outcome of 5FU-based therapy. TS levels in tumor samples can be determined with radiochemical enzyme assays, RT-PCR, and immunohistochemical staining. We validated TS immunohistochemistry with a polyclonal rabbit anti-human TS antibody using the avidin-biotin method. This antibody can be used on paraffin-embedded, formalin-fixed material using an antigen retrieval method with citrate buffer and microwave treatment. The antibody shows a granular cytosolic staining pattern. The reproducibility in cross-sections from colorectal tumors from 50 patients was 90% and the interobserver variability was acceptable with a kappa of 0.45. On Western blotting it detects purified TS at 36 kD, while in 5FU-treated cells the ternary complex between FdUMP, TS, and 5, 10-methylene-tetrahydrofolate is clearly visible at 38 kD, with no other interfering bands. In a separate set of tumors, immunostaining was compared with enzyme levels; Western blots correlated with enzyme levels. Because both this polyclonal antibody and the monoclonal antibody TS-106 are being used for large-scale studies, we also determined whether they could be used interchangeably. No differences were observed. This polyclonal antibody is specific and gives reproducible results. A study on a larger scale is ongoing to determine the role of TS as a predictive parameter in patients with colorectal cancer treated either with postoperative adjuvant 5FU/levamisole or with surgery only.
Animals↗
Evaluation of a probabilistic model for staging of oesophageal carcinoma.
With the help of two experts in gastrointestinal oncology from the Netherlands Cancer Institute, Antoni van Leeuwenhoekhuis, a decision-support system is being developed for patient-specific therapy selection for oesophageal carcinoma. The kernel of the system is a probabilistic model describing the characteristics of oesophageal carcinoma and the pathophysiological processes of invasion and metastasis. Using data from 185 patients, an evaluation study of the model was conducted. We found that for 86% of the patients, the model established the stage of the patient's carcinoma correctly.
Artificial Intelligence↗
Carcinoid tumors.
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3-Iodobenzylguanidine↗
Bioanalysis of m-iodobenzylguanidine in plasma by high-performance liquid chromatography after derivatization with benzoin.
A sensitive chromatographic assay has been developed for m-iodobenzylguanidine (MIBG) in human plasma based on the derivatization with benzoin. MIBG is first isolated from plasma using solid-phase extraction on a cyanopropyl-modified silica phase. After evaporation of the eluate, a fluorescent derivative is formed using benzoin. The derivative is analysed by reversed-phase liquid chromatography using a mixture 60% (v/v) acetonitrile, 30% (v/v) water and 10% (v/v) of the 0.5 M Tris buffer (pH 8.0) as the eluent and fluorescence detection at 320 nm for excitation and 435 nm for emission, respectively. In the evaluated concentration range (2-200 ng/ml) precisions < or = 10% and accuracies in between 90 and 100% have been found, with 2 ng/ml being the lower limit of quantification using a 0.5-ml plasma sample volume. The assay can also be used without the internal standard benzylguanidine. The assay was successfully used to obtain a pharmacokinetic curve of MIBG.
3-Iodobenzylguanidine↗
[Periodic colonoscopic examinations of persons with a positive family history for colorectal cancer. Work Group 'Hereditary non-polyposis- colon-rectum cancers'].
Individuals with one first-degree relative with colorectal cancer diagnosed before age 45 years and those with two first-degree relatives with colorectal cancer run a significantly increased risk (relative risk: 4-6) of developing colorectal cancer. Based on calculation of the mortality due to colorectal cancer for the age group 50-70 years (which is higher than the mortality due to breast cancer) surveillance may be justified, e.g. by colonoscopy at 5-year intervals from the age of 45-50. The total number of people in the Netherlands in this high risk group is estimated at 10,000. The authors conclude that prospective studies are needed to assess the cost-effectiveness of such a programme.
Aged↗
[Carcinoid tumors of the intestines: developments in the Netherlands for diagnosis and palliative treatment].
Carcinoid tumours in the intestine are slowly growing neuroendocrine tumours. Patients as a rule report symptoms of the carcinoid syndrome: attacks of diarrhoea and of flushing. When the earliest symptoms manifest themselves, metastases are already present, virtually always localized in the liver. At a late stage, heart failure may occur, difficult to treat and caused by fibrosis of the tricuspid valve in the presence of protractedly raised blood serotonin levels. To diagnose carcinoid tumours, use is made of radioactive substances binding to hormone receptors such as 131I-MIBG and 111-In-octreotide. When multiple metastases exist, only palliative treatment is possible. The drugs used are the somatostatin analog octreotide, interferon alpha, radioactive MIBG and non-radioactive MIBG; these drugs may also be used in combination. The therapies mentioned have approximately the same effect: symptoms improve in 60-80%, while 30-50% show a biochemical response, i.e. decrease of the number of breakdown products in the urine of the hormones produced by the tumour; tumour size decreases in 0-12%.
Carcinoid Heart Disease↗
[The role of genetic factors in the development of gastric cancer].
In general, a genetic predisposition to a tumour disease such as gastric cancer is postulated in patients with cancer at an unusually early age or when several relatives are affected. A clear definition of hereditary gastric cancer is lacking. Two types of families may be distinguished: kindreds with gastric cancer only (site-specific), and kindreds with gastric as well as colorectal cancer, representing the hereditary non-polyposis colon cancer (HNPCC) syndrome. A genetic predisposition is presumed in young patients with a diffuse type of gastric cancer, in contrast to the intestinal type which is associated with atrophic gastritis and older age. A variety of genetic abnormalities in tumour tissue have been described, e.g. mutations in genes involved in DNA repair. Helicobacter pylori plays an important role in the aetiology, but the interaction with genetic factors is unknown.
Adult↗
Clinical and endoscopic features of melanoma metastases in the upper GI tract.
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Adult↗
Controversies and consensus in the diagnosis, work-up and treatment of gastric lymphoma: an international survey.
BACKGROUND: Variations in diagnostic criteria and staging procedures in cancer patients have important consequences for patient selection and often preclude meaningful comparison of published series. In gastric lymphoma, these effects will play a role, since diagnostic criteria are controversial. Moreover, staging procedures and therapeutic choices are influenced by insights from different clinical specialisms. METHODS: To review the management of gastric lymphoma, formatted questionnaires were mailed to leading institutes with a special interest in this field in Europe, the United States and Japan. RESULTS: Nineteen centers agreed to contribute. Minimum histological criteria varied among pathologists with a notable influence of the classification system used in the different countries. Detailed evaluation of the lymphoma distribution in the gastric wall and routine staging of the GI-tract differed between groups leaded by medical oncologists and gastroenterologists. This results in basically different patient selections and bias in treatment outcome. Similar effects were recorded for the role of gastric resection and radiotherapy. CONCLUSIONS: This study gives insight in the basis of the decisions that result in different approaches in the management of gastric MALT-NHL and in the effects for patient selection and treatment results and may help in the design of future clinical trials.
Antineoplastic Agents↗
Long-term palliation in metastatic carcinoid tumours with various applications of meta-iodobenzylguanidin (MIBG): pharmacological MIBG, 131I-labelled MIBG and the combination.
Carcinoid tumours are rare, but well known for their characteristic presentation with diarrhoea and flushes due to overproduction of serotonin in the case of liver metastases. Treatment is mainly based on the reduction of vasoactive peptide hypersecretion and symptomatic improvement Octreotide and interferon are widely applied and effective treatment options to induce symptomatic improvement and, to a lesser extent, biochemical response. The main drawbacks, however, are the need for frequent injections and/or the occurrence of side effects. A rather new approach is the application of meta-iodobenzylguanidine (MIBG), which resembles noradrenalin and serotonin. In carcinoid patients, MIBG is taken up in the tumour cells and stored in the neurosecretory granules. When labelled with 131 iodine, radionuclide imaging is positive in up to 70% of the patients. In these patients, two cycles of a therapeutic dose of radioactive MIBG may induce long-lasting palliation (8 months) by internal irradiation. Also, the non-radioactive MIBG compound may be effective in palliation, even in patients with a negative scan. The mode of action is based on specific tumour acidification as found in animal models, and/or based on its effect as a false neurotransmittor. Three case reports demonstrate different therapeutic possibilities of MIBG: 1) symptomatic relief with unlabelled MIBG, which is a safe and simple treatment; 2) the longterm palliation following radioactive treatment; and 3) an additional new aspect of predosing with unlabelled MIBG followed by radioactive MIBG led to improved tumour targeting and impressive clinical response.
3-Iodobenzylguanidine↗
A cost-effectiveness analysis of colorectal screening of hereditary nonpolyposis colorectal carcinoma gene carriers.
BACKGROUND: It has been estimated that the prevalence of carriers of a mutated mismatch repair (MMR) gene among the general population in Western countries is between 5 and 50 per 10,000. These carriers have a risk of >85% of developing colorectal carcinoma (CRC) and therefore need careful follow-up. The objective of this study was to analyze the cost-effectiveness of CRC surveillance of carriers of a mutated MMR gene. METHODS: The authors constructed a model to estimate the potential health effects (life expectancy) and healthcare costs of two strategies: 1) surveillance, with colonoscopy every 2-3 years, and 2) no CRC surveillance. Estimates of the lifetime risk of developing CRC and the stage distribution of CRC for symptomatic patients were derived from the Dutch hereditary nonpolyposis colorectal carcinoma (HNPCC) registry. The CRC stage specific relative survival rates and the effectiveness of surveillance in preventing or detecting cancer early were based on Finnish studies. The costs of surveillance and treatment were derived from recent American studies. RESULTS: The results showed that 1) surveillance of gene carriers led to an increase in life expectancy of 7 years, and 2) the costs of surveillance under a wide range of assumptions are less than the costs of no CRC surveillance. CONCLUSIONS: CRC surveillance of HNPCC gene carriers appears to be effective and considerably less costly than no CRC surveillance and therefore deserves to be supported by governmental agencies and health insurance organizations.
Adult↗
[Sealing esophagobronchial fistulae: better results with self expanding stents than with an esophagobronchial fistula].
OBJECTIVE: To compare the results of plastic endoprostheses and of self expanding stents in patients with an esophagobronchial fistula. DESIGN: Retrospective, descriptive. SETTING: Nederlands Kanker Instituut/Antoni van Leeuwenhoek Ziekenhuis, Amsterdam, the Netherlands. METHOD: Forty-two patients with an esophagobronchial fistula caused by a malignant tumour in the oesophagus, lungs or mediastinum were fitted with an endoprosthesis during the period 1 January 1991-31 August 1995. Use was made initially of a plastic endoprosthesis with a special tulip funnel (n = 24), later of a coated self expanding stent (n = 18). In seven patients, the fistula had been the first manifestation of the tumour; in 35, a recurrence after earlier treatment was involved. The initial characteristics (sex, age, diagnosis, earlier therapy, signs and symptoms) were the same in both groups. RESULTS: Dilatation immediately before insertion of a plastic endoprosthesis was necessary in 23 patients (96%); such dilatation was necessary in four of the patients (22%) fitted with a self expanding stent. Complete sealing of the fistula was achieved in 19 (79%) and 15 (83%) patients, respectively. Reoperations were necessary in eight (33%) and three (17%) patients. Early major complications occurred in four (17%) and two (11%) patients. CONCLUSION: The selfexpanding stent was faster and easier to insert than a plastic endoprosthesis, and effective in sealing an oesophagobronchial fistula.
Bronchial Fistula↗
Comment on radiotherapy for treatment of localized gastrointestinal non-Hodgkin's lymphoma.
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Biopsy↗
Expandable stents compared to conventional plastic endoprostheses in malignant oesophageal obstruction, especially in cardiac cancer and fistulas: the experience of the Netherlands Cancer Institute.
BACKGROUND: Advanced oesophageal carcinoma usually causes debilitating dysphagia. An endoprosthesis can offer adequate palliation. The self-expandable metal stents provide several advantages over the plastic endoprostheses: less traumatic introduction and stronger attachment to the oesophageal wall. OBJECTIVE: To evaluate whether the self-expandable stents are more effective, especially in the technically challenging group of patients with a cardiac carcinoma or a fistula. SETTING: A single-institution study (cancer hospital). METHODS: A retrospective study of 132 consecutive patients (92 men and 40 women; median age 67 years) in whom a stent was inserted between 1991 and 1996. A plastic stent was applied in 72 patients, and from 1994 onwards an expandable stent in 60 subsequent patients. RESULTS: Overall technical success rate was high for both types of stents: 93 vs 88%. Clear improvement of dysphagia occurred more often with the expandable stents (80%) compared to the plastic stents (62%). Unfortunately, loss of appetite remained a problem in 30% of the patients. In the more troublesome subgroup of cardiac carcinoma (n = 55) and (imminent) fistula (n = 42) stenting was equally effective. Early complications were significantly less often encountered for the self-expandables: 3 vs 45%, the same was true for insertion related mortality: 0 vs 10%. Also the need for reintervention was less frequent: 12 vs 23%. This was especially on the account of the plastic stent in fistulas. CONCLUSIONS: Technical success rate was excellent for all types of stents, but in particular for the self-expandable stents which were also associated with fewer side effects. The subgroups of fistula and cardia carcinoma did equally well, probably related to adequate choice of stent.
Adult↗
Computer-based decision support in the management of primary gastric non-Hodgkin lymphoma.
Primary non-Hodgkin lymphoma of the stomach is a rare disorder for which clinical management has not yet been settled completely. Faced with the many uncertainties associated with the selection of a treatment for a patient with this disorder, it is difficult to determine the treatment that is optimal for the patient, as well as the prognosis to be expected. The development of a decision-theoretic model of non-Hodgkin lymphoma of the stomach is described. The model aims to assist the clinician in exploring various clinical questions, among others questions concerning prognosis and optimal treatment. Central to the model is a probabilistic network that offers an explicit representation of the uncertainties underlying the decision-making process. The model has been incorporated in a decision-support system. Preliminary evaluation results indicate that the performance of the model in its present form matches the performance of experienced clinicians.
Combined Modality Therapy↗