Monte Carlo calculation of dose enhancement by neutron capture of 10B in fast neutron therapy

Since 1978 the Essen Medical Cyclotron Facility has been used for fast neutron therapy. The treatment of deep-seated tumours by d(14) + Be neutron beam therapy (mean energy = 5.8 MeV) is still limited because of the steep decrease in depth-dose distribution. The interactions of fast neutrons in tissue leads to a thermal neutron distribution. These partially thermalized neutrons can be used to produce neutron capture reactions with 10B. Thus incorporation of 10B in tumours treated with fast neutrons will increase the relative local tumour dose due to the reaction 10B (n, alpha) 7Li. The magnitude of dose enhancement by 10B depends on the distribution of the thermal neutron fluence, 10B concentration, field size of the neutron beam, beam energy and the specific phantom geometry. The slowing down of the fast neutrons, resulting in a thermal neutron distribution in a phantom, has been computed using a Monte Carlo model. This model, which includes a deep-seated tumour, was experimentally verified by measurements of the thermal neutron fluence rate in a phantom using neutron activation of gold foil. When non-boronated water phantoms were irradiated with a total dose of 1 Gy at a depth of 6 cm, the thermal fluencies at this depth were found to be 2 x 10(10) cm-2. The absorbed dose in a tumour with 100 ppm 10B, at the same depth, was enhanced by 15%.     

A comparison between combined neutron- and telecobalt-therapy with telecobalt-therapy alone for cancer of the bronchus

The difference in response of human tumours to high and low LET radiation has been investigated in a series of inoperable, histologically confirmed bronchial carcinomas. One hundred and forty-nine were treated with low LET radiation alone (60Co gamma rays) and 108 with a combination of gamma rays and fast neutrons of mean energy 6 MeV, one-fifth to one-third of the effective dose being from neutrons. The response was analysed by histological examination of the autopsy specimens. Tumour cell destruction was found to be significantly greater in the neutron-treated series. The two series were not strictly randomized but were closely similar to terms of tumour volume, histological grade and total treatment time. The sequence of treatments with neutrons and gamma rays (N-gamma, gamma-N, gamma-N -gamma) was found to have no influence on the results.     

Combined use of FLUKA and MCNP-4A for the Monte Carlo simulation of the dosimetry of 10B neutron capture enhancement of fast neutron irradiations

Boron neutron capture enhancement (BNCE) of the fast neutron irradiations use thermal neutrons produced in depth of the tissues to generate neutron capture reactions on 10B within tumor cells. The dose enhancement is correlated to the 10B concentration and to thermal neutron flux measured in the depth of the tissues, and in this paper we demonstrate the feasibility of Monte Carlo simulation to study the dosimetry of BNCE. The charged particle FLUKA code has been used to calculate the primary neutron yield from the beryllium target, while MCNP-4A has been used for the transport of these neutrons in the geometry of the Biomedical Cyclotron of Nice. The fast neutron spectrum and dose deposition, the thermal flux and thermal neutron spectrum in depth of a Plexiglas phantom has been calculated. The thermal neutron flux has been compared with experimental results determined with calibrated thermoluminescent dosimeters (TLD-600 and TLD-700, respectively, doped with 6Li or 7Li). The theoretical results were in good agreement with the experimental results: the thermal neutron flux was calculated at 10.3 X 10(6) n/cm2 s1 and measured at 9.42 X 10(6) n/cm2 s1 at 4 cm depth of the phantom and with a 10 cm X 10 cm irradiation field. For fast neutron dose deposition the calculated and experimental curves have the same slope but different shape: only the experimental curve shows a maximum at 2.27 cm depth corresponding to the build-up. The difference is due to the Monte Carlo simulation which does not follow the secondary particles. Finally, a dose enhancement of, respectively, 4.6% and 10.4% are found for 10 cm X 10 cm or 20 cm X 20 cm fields, provided that 100 micrograms/g of 10B is loaded in the tissues. It is anticipated that this calculation method may be used to improve BNCE of fast neutron irradiations through collimation modifications.     

A morphometric analysis of glomerular and tubular alterations following fast-neutron irradiation of the pig and monkey kidney

PURPOSE: The morphologic responses of the pig and monkey kidney to fractionated fast-neutron irradiation were assessed. METHODS AND MATERIALS: The right kidney of approximately 14-week-old female Large White pigs was irradiated with 6.6-12.2 Gy of fast neutrons (42 MeVd-->Be) given as 12 fractions over 18 days; the left kidney served as the contralateral unirradiated kidney. Both kidneys were removed at necropsy 2 years postirradiation. In addition, the remaining hypertrophied kidney of four unilaterally nephrectomized adult rhesus monkeys was irradiated with a total dose of 11.0 Gy fast neutrons (45 MeVp-->Be) given in an identical fractionation regimen to that used in the pig studies. These kidneys were removed when the animals exhibited renal failure, between 32-94 weeks postirradiation. Glomeruli were assessed for the presence of pathologic features, including intercapillary eosinophilic material (ICE), ectatic capillaries, thrombi, hemorrhage, and sclerosis. The relative proportion of renal cortex occupied by glomeruli, interstitium, normal, or abnormal tubules was determined using a Chalkley point grid. RESULTS: The incidence of normal glomeruli, ectatic capillaries, thrombosis, and periglomerular fibrosis were significantly different in the irradiated pig kidneys compared with the unirradiated contralateral kidneys (p < or = 0.02). Linear regression analysis demonstrated a significant dose relationship in terms of normal glomeruli, ectatic capillaries, and ICE (r > or = 0.64; p < or = 0.04). Irradiation was also associated with a significant (p < 0.0001) decrease and increase in the volume of renal cortex occupied by normal and abnormal tubules, respectively. Similar morphometric changes were noted in the irradiated monkey kidneys. CONCLUSIONS: The morphologic changes seen in the pig and monkey kidney after fractionated irradiation with fast neutrons are similar to those previously noted after single-dose or fractionated-photon irradiation. These findings support the hypothesis that the development of radiation nephropathy in these various models involves common pathophysiological mechanisms.     

Radiographic diagnosis: arachnoid cyst in a dog

Lauren's intestinal type of gastric cancer was proposed to be dependent on long-term environmental factors and is always preceded by chronic premalignant change. A cohort study was performed and demonstrated an increased cancer risk of gastric remnant after gastric surgery for benign disease. It is generally believed that after gastrectomy the residual stomach has an environmental change and, thus, enters a neoplastic process. Based on the carcinogenic theory of intestinal-type tumour, it would be of interest to know whether the intestinal-type tumour is more common in gastric remnant cancer. Forty patients with gastric remnant cancer had gastrectomy in the Veterans General Hospital-Taipei. Another 683 patients with primary gastric carcinoma underwent resection and were used as controls. The clinical characteristics, tumour stage and intestinal-type tumour were analysed in gastric remnant cancer and were compared with the various portions of primary gastric carcinoma. Although the overall distribution of intestinal-type carcinoma in gastric remnant (45%) was no different to that of any other portion of stomach cancer, intestinal-type carcinoma was more common in the early stage of gastric remnant (73%) and distal stomach (73%), but not in the proximal stomach (50%), which was supposed to have the same characteristics as the gastric remnant because of identical anatomic location. More than expected, intestinal-type carcinoma in early gastric remnant cancer together with a long incubation interval between primary surgery and later tumour occurrence were compatible with the theory of carcinogenesis of intestinal-type carcinoma.     

In-phantom dosimetry and spectrometry of photoneutrons from an 18 MV linear accelerator

A combination of three superheated drop detectors with different neutron energy responses was developed to evaluate dose-equivalent and energy distributions of photoneutrons in a phantom irradiated by radiotherapy high-energy x-ray beams. One of the three detectors measures the total neutron dose equivalent and the other two measure the contributions from fast neutrons above 1 and 5.5 MeV, respectively. In order to test the new method, the neutron field produced by the 10 cm X 10 cm x-ray beam of an 18 MV radiotherapy accelerator was studied. Measurements were performed inside a tissue-equivalent liquid phantom, at depths of 1, 5, 10 and 15 cm and at lateral distances of 0, 10, and 20 cm from the central axis. These data were used to calculate the average integral dose to the radiotherapy patient from direct neutrons as well as from neutrons transmitted through the accelerator head. The characteristics of the dosimeters were confirmed by results in excellent agreement with those of prior studies. Track etch detectors were also used and provided an independent verification of the validity of this new technique. Within the primary beam, we measured a neutron entrance dose equivalent of 4.5 mSv per Gy of photons. It was observed that fast neutrons above 1 MeV deliver most of the total neutron dose along the beam axis. Their relative contribution increases with depth, from about 60% at the entrance to over 90% at a depth of 10 cm. Thus, the average energy increases with depth in the phantom as neutron spectra harden.     

Enhanced expression of cytochrome P450 in stomach cancer

The cytochromes P450 have a central role in the oxidative activation and detoxification of a wide range of xenobiotics, including many carcinogens and several anti-cancer drugs. Thus the cytochrome P450 enzyme system has important roles in both tumour development and influencing the response of tumours to chemotherapy. Stomach cancer is one of the commonest tumours of the alimentary tract and environmental factors, including dietary factors, have been implicated in the development of this tumour. This type of tumour has a poor prognosis and responds poorly to current therapies. In this study, the presence and cellular localization of several major forms of P450, CYP1A, CYP2E1 and CYP3A have been investigated in stomach cancer and compared with their expression in normal stomach. There was enhanced expression of CYP1A and CYP3A in stomach cancer with CYP1A present in 51% and CYP3A present in 28% of cases. In contrast, no P450 was identified in normal stomach. The presence of CYP1A and CYP3A in stomach cancer provides further evidence for the enhanced expression of specific forms of cytochrome P450 in tumours and may be important therapeutically for the development of anti-cancer drugs that are activated by these forms of P450.     

Changes in RBE of 14-MeV (d + T) neutrons for V79 cells irradiated in air and in a phantom: is RBE enhanced near the surface?

PURPOSE: The relative biological effectiveness (RBE) for inactivation of V79 cells was determined as function of dose at the Heidelberg 14-MeV (d + T) neutron therapy facility after irradiation with single doses in air and at different depths in a therapy phantom. Furthermore, to assess the reproducibility of RBE determinations in different experiments we examined the relationship between the interexperimental variation in radiosensitivity towards neutrons with that towards low LET 60Co photons. METHODS: Clonogenic survival of V79 cells was determined using the colony formation assay. The cells were irradiated in suspension in small volumes (1.2 ml) free in air or at defined positions in the perspex phantom. Neutron doses were in the range, Dt = 0.5-4 Gy. 60Co photons were used as reference radiation. RESULTS: The radiosensitivity towards neutrons varied considerably less between individual experiments than that towards photons and also less than RBE. However, the mean sensitivity of different series was relatively constant. RBE increased with decreasing dose per fraction from RBE = 2.3 at 4 Gy to RBE = 3.1 at 0.5 Gy. No significant difference in RBE could be detected between irradiation at 1.6 cm and 9.4 cm depth in the phantom. However, an approximately 20% higher RBE was found for irradiation free in air compared with inside the phantom. Combining the two effects, irradiation with 0.5 Gy free in air yielded an approximately 40% higher RBE than a dose of 2 Gy inside the phantom. CONCLUSION: The measured values of RBE as function of dose per fraction within the phantom is consistent with the energy of the neutron beam. The increased RBE free in air, however, is greater than expected from microdosimetric parameters of the beam and may be due to slow recoil protons produced by interaction of multiply scattered neutrons or to an increased contribution of alpha particles from C(n, alpha) reactions near the surface. An enhanced RBE in subcutaneous layers of skin combined with an increase in RBE at low doses per fraction outside the target volume could potentially have significant consequences for normal tissue reactions in radiotherapy patients treated with fast neutrons.     

Comparisons of pulmonary and sinonasal lesions in patients with cystic fibrosis. Evaluation using computerized tomography

INTRODUCTION: Cystic fibrosis is a recessive genetic systemic exocrinopathy caused by a variety of mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR). The disease is characterized by alterations of the secretions, which become thickened and viscous. Both the paranasal sinuses and the lung parenchyma are involved in all cases. The aim of this study was to assess a correlation between the rhinosinusal and lung parenchyma changes in cystic fibrosis patients. MATERIAL AND METHODS: Eighteen patients (11 men and 7 women, age range: 8 to 22 years) were examined with chest HRCT and sinonasal low dose CT. Lung symptoms were found in all patients; 13 of them, also affected with rhinosinusal symptoms, had been examined with ENT and nasal endoscopy. The other 5 patients, without rhinosinusal symptoms and previously examined with ENT, were evaluated as control group. Chest CT was performed with the high-resolution technique, 2 mm slice thickness and 10 mm table feed. Rhinosinusal CT was performed with the low dose technique, acquiring contiguous 2-4 mm thickness coronal sections. The CT patterns were analyzed by two radiologists and scored as slight, medium and diffuse involvement of both districts. RESULTS: No statistically significant correlation between lung and sinonasal damage was found in our study. Parenchymal lung involvement appeared more severe than sinonasal involvement in 14/18 patients. The retention of secretions in the paranasal sinuses, even if limited, was demonstrated in all symptomatic and asymptomatic patients. CONCLUSIONS: The absence of correlation between pulmonary and sinonasal damage and more generally, the different severity of cystic fibrosis can be caused by different allele mutations of the cystic fibrosis transmembrane conductance regulator gene, the most frequent of which is Delta F-508.     

Neutron radiobiology revisited

The present paper reviews the experimental results of normal tissue and tumour studies in animals. The dose per fraction dependence of the RBE in normal tissues has been long recognised, together with the steeper increase of RBE at low doses for late responding tissues compared with acute reactions. The dose dependence for tumours is more complex, because of hypoxia and reoxygenation, as well as differences in repair capability after high LET damage. A comparison of tumour and normal tissue RBE values shows that there is little experimental evidence for a therapeutic advantage at clinically relevant doses. In particular, the RBE for slow growing tumours is even lower than that for the faster growing mouse tumours. The reasons for the loss of expected neutron benefits in clinically relevant experiments are discussed. The disappointing prospects for neutrons are contrasted with the current multifactorial approaches to overcoming resistance to more conventional low LET radiations, including acceleration, hyperfractionation and several types of hypoxic cell radiosensitizers.     

Neutron induced recoil protons of restricted energy and range and biological effectiveness

Low energy neutrons (<2 MeV), those of principal concern in radiation protection, principally initiate recoil protons in biological tissues. The recoil protons from monoenergetic neutrons form rectangular distributions with energy. Monoenergetic neutrons of different energies (<2 MeV) will then produce overlapping recoil proton spectra. By overlapping the effects of individual deposition events, determined microdosimetrically for cell nuclear dimensions, from such neutron beams the biological effectiveness of recoil protons within defined energy and range bounds can be determined. Here chromosomal aberrations per cell have been quantified following irradiation of Vicia faba cells with monoenergetic neutrons of 230, 320, 430, and 1,910 keV. Aberration frequencies from cells from part of the cell cycle, thereby limiting nuclear dimensions, were linearly related to dose and to the frequency of proton recoils per nucleus. The 320 keV neutrons were the most biologically effective per unit absorbed dose and 430 keV neutrons most effective per recoil proton, with 21% of recoils inducing aberrations. After extraction of effectiveness per proton recoil within each energy and range bounds (0-230, 230-320, 320-430, and 430-1,910 keV), it was concluded that recoil protons with energies of about 200-300 keV, traveling 2.5-4 microm and depositing energy at about 80 keV micrometer(-1), are more efficient at aberration induction than those recoil protons of lesser range though near equivalent LET and those of greater range through lesser LET. This approach allows for assessment of the biological effectiveness of individual energy deposition events from low energy neutrons, the lowest dose a cell can receive, and provides an alternative to considerations of relative biological effectiveness.     

An efficient method for cloning in-frame fusion protein genes

BACKGROUND: Transhiatal oesophagectomy is an accepted approach for the treatment of carcinoma of the oesophagus. However, experience of this technique in benign diseases is limited. METHODS: Transhiatal oesophagectomy was done in 29 patients for benign oesophageal conditions including corrosive stricture (21), achalasia of the cardia (four), tuberculosis (one), mediastinal fibrosis (one), Crohn's disease (one) and peptic stricture (one). Dysphagia was the predominant symptom in all patients; strictures had all previously been dilated repeatedly. The stomach was used as an oesophageal substitute in 24 patients; in five with a scarred stomach due to damage by a corrosive agent, oesophagocoloplasty was performed. Resection and reconstruction were done in one stage in 25 patients; four with poor nutritional status had a two-stage procedure. RESULTS: There was no perioperative death. Complications encountered were recurrent laryngeal nerve palsy (six patients) which was mostly transient, anastomotic leak (seven) and stenosis (eight). Postoperative function of the intrathoracic stomach was satisfactory. CONCLUSION: Transhiatal oesophagectomy is a safe and satisfactory procedure for benign obstructive conditions of the oesophagus.     

Tissue and blood CEA levels in stomach cancer

The assays of serum CEA is a useful prognostic marker in patients with stomach cancer. In this study pre-operative serum CEA and tissue CEA in tumour or biopsy were assayed in a group of patients with gastric carcinoma in order to assess their prognostic roles. Based on an analysis of the results the authors affirm that high serum CEA levels in patients with advanced stages of stomach cancer indicate a fatal prognosis, and likewise the finding of tissue CEA in loco-regional lymph nodes at the same concentration as that in the primary tumour is also the sign of a severe prognosis.     

Necrotizing infundibulo-hypophysitis: a unique syndrome of diabetes insipidus and hypopituitarism

Clinical, radiological, histological, and anatomical features in 2 patients with necrotizing infundibulo-hypophysitis are reported. The patients presented with a combination of diabetes insipidus and hypopituitarism. Each was found to have a sellar mass lesion with an abnormally thickened enlarged pituitary stalk that intensively enhanced on contrast magnetic resonance imaging. They were suspected to have pituitary tumors with suprasellar extension. However, tissue obtained at transphenoidal surgery revealed necrosis, fibrosis, and chronic inflammation; there was no evidence of infiltrative, infective, or neoplastic disease processes. Postoperatively, they continued to have diabetes insipidus and hypopituitarism despite radiological improvement and steroid therapy. Several clinical and anatomical features distinguish these 2 cases from classical lymphocytic hypophysitis, the most common entity in the differential diagnosis. Specifically, diabetes insipidus has not been observed preoperatively in 30 cases of lymphocytic hypophysitis, but was present in the 2 cases reported. Histological evidence of tissue necrosis present in these 2 cases is not a feature of lymphocytic hypophysitis. Pituitary stalk involvement on magnetic resonance imaging or computed tomographic scan present in these 2 cases is highly unusual in lymphocytic hypophysitis. Finally, 29 of 30 cases of lymphocytic hypophysitis were females, whereas the 2 cases reported are men. On the basis of these disparate findings, we suggest that these 2 cases represent a unique syndrome, which may be recognized clinically and radiologically.     

Analysis of the radiobiology of ytterbium-169 and iodine-125 permanent brachytherapy implants

Recently, Yb-169 has been considered as a potential replacement for I-125 and Pd-103 in permanent implants. In spite of the uncertainties in the parameters necessary for an accurate radiobiological modelling, the linear quadratic model can be useful in the comparative evaluation of the radiotherapeutic merit of similar implants. In order to find out if a Yb-169 permanent implant can be made biologically 'equivalent' to an I-125 implant, we studied the dependence of local control on the tumour cell radiosensitivity and on the balance between the rate of tumour cell killing and tumour cell proliferation, for rapidly and slowly proliferating tumours. The extrapolated response dose (ERD) has been calculated for tumour and late reacting normal tissue for both types of implants and the possible biological restrictions due to the normal tissue tolerance have been discussed. Our theoretical analysis is consistent with the clinical results published for I-125 permanent implants in prostate tumours and meningiomas. It predicts that Yb-169, which has only recently been used in human tumours, can provide comparable tumour control for permanent implants in slowly proliferating tumours with an initial dose rate of 13 cGy h-1. Control might be extended to rapidly proliferating tumours by increasing the initial dose rate within a range consistent with an acceptable level of normal tissue late reaction.     

Change in oxygen enhancement ratio with depth in tissue-equivalent material for a collimated beam of fast neutrons

Survival of reproductive capacity of murine leukaemia P-388 cells was assayed in vivo after the cells had been irradiated in vitro under aerobic or hypoxic conditions with collimated beams of X rays or 16 MeV D-Be fast neutrons at various depths in tissue-equivalent phantom material. The response to X-irradiation was the same in the absence of the phantom and at 8-7 cm depth. The response to fast neutrons under aerobic conditions was unchanged from 0 to 23 cm depth within the phantom. However, under hypoxic conditions, the dose-response curve for fast neutrons became significantly steeper with increasing depth in the phantom. The OER decreased from 2-0 in the absence of the phantom to 1-5 at 15 cm deep.     

Drug-induced linear IgA disease: target antigens are heterogeneous

BACKGROUND: Colonic strictures represent an advanced stage of fibrosing colonopathy in patients with cystic fibrosis. AIMS: To clarify whether ultrasonography can identify patients with an early stage of fibrosing colonopathy and to determine clinical factors that influence bowel wall thickening. PATIENTS: Ninety patients with cystic fibrosis, median age 10 years, and 46 healthy controls, median age 13 years, were investigated. METHODS: Bowel wall thickness was measured by ultrasound in a prospective study. RESULTS: In cystic fibrosis, wall thickness of both small intestine and colon was significantly (p < 0.0001) higher than in controls; 81% of patients with cystic fibrosis had a maximum colon wall thickness at any site of 2 mm or more, a value that was never reached by controls. The maximum colon wall thickness was 6.5 mm. Bowel wall thickness was unchanged at re-examination after one year. There was no progression even with high dose pancreatic supplements. There was no association between bowel wall thickness and clinical features such as previous meconium ileus, intestinal resection, distal intestinal obstruction syndrome, abdominal pain, or pancreatic enzyme dose. CONCLUSIONS: There is genuine intestinal involvement in cystic fibrosis; in a few cases this could lead to fibrosing colonopathy.     

CT abnormalities of the pituitary in hyperprolactinaemic women with normal or equivocal sellae radiologically

Sixteen young women with hyperprolactinaemia and normal or equivocal sella in radiographs underwent computed tomography using a Siemens Somatom II. In all but one case an abnormality was found. The sella was full in seven and partially empty in nine. A tumour was visible in six of the full and in four of the partially empty sellae. All but one of the 10 tumours was unilateral, and in seven the pituitary stalk was deviated away from the tumour. After administration of intravenous contrast (Urografin) four tumours showed diffuse enhancement, four ring enhancement, and two enhanced less than adjacent normal pituitary tissue. Two of the tumours have been subsequently shown histologically to be prolactinomas. Prolactin response to thyrotrophin-releasing hormone predicted a tumour in seven out of eight with visible tumours but also in three out of four without visible tumours; using metoclopramide, a tumour was predicted in six out of seven with tumours, but again in three out of four without visible tumours. Such results question the value of dynamic tests for the discrimination of tumours. We conclude that practically all women with sustained hyperprolactinaemia and a normal or equivocal sella radiologically have pituitary disease.     

Establishment of an animal model for pulmonary fibrosis in mice using monocrotaline

A preliminary attempt at experimental induction of pulmonary fibrosis in which male ICR mice received 15 weekly sc injections of 200 or 100 mg/kg monocrotaline (MC) revealed that most animals treated with the larger dose died of severe interstitial pneumonia, whereas those given 100 mg/kg exhibited only relatively slight lung injury. Based on these results, male mice were administered sc injections of 200 and 100 mg/kg MC once a week for 9 and 18 times, respectively, and then maintained without any further treatment until week 28 after the start. Mice treated with 200 mg/kg MC showed severe pulmonary damage and died by week 25. Mortalities also occurred in the 100-mg group from week 16, with 11 of 40 animals surviving at the termination of the experiment. Histologically, both dose groups demonstrated severe interstitial pneumonia and/or pulmonary fibrosis. Ultrastructurally, inflammatory edema possibly attributable to injuries of alveolar capillary endothelial cells was observed in the high-dose group at week 8, and there was a remarkable increase in collagen fibers in alveolar septa in this group thereafter. The present study results suggest that lung injuries induced by MC treatment progress to irreversible lung fibrosis and that this animal model may have advantage for studying the pathogenesis of lung cancers in patients with pulmonary fibrosis.     

Human papillomavirus infection and esophageal cancer: a nationwide seroepidemiologic case-control study in Sweden

BACKGROUND: Despite being immunogenic, gastric cancers overcome antitumour immune responses by mechanisms that have yet to be fully elucidated. Fas ligand (FasL) is a molecule that induces Fas receptor mediated apoptosis of activated immunocytes, thereby mediating normal immune downregulatory roles including immune response termination, tolerance acquisition, and immune privilege. Colon cancer cell lines have previously been shown to express FasL and kill lymphoid cells by Fas mediated apoptosis in vitro. Many diverse tumours have since been found to express FasL suggesting that a "Fas counterattack" against antitumour immune effector cells may contribute to tumour immune escape. AIM: To ascertain if human gastric tumours express FasL in vivo, as a potential mediator of immune escape in stomach cancer. SPECIMENS: Thirty paraffin wax embedded human gastric adenocarcinomas. METHODS: FasL protein was detected in gastric tumours using immunohistochemistry; FasL mRNA was detected in the tumours using in situ hybridisation. Cell death was detected in situ in tumour infiltrating lymphocytes using terminal deoxynucleotidyl transferase mediated dUTP nick end labelling (TUNEL). RESULTS: Prevalent expression of FasL was detected in all 30 resected gastric adenocarcinomas examined. In the tumours, FasL protein and mRNA were co-localised to neoplastic gastric epithelial cells, confirming expression by the tumour cells. FasL expression was independent of tumour stage, suggesting that it may be expressed throughout gastric cancer progression. TUNEL staining disclosed a high level of cell death among lymphocytes infiltrating FasL positive areas of tumour. CONCLUSIONS: Human gastric adenocarcinomas express the immune downregulatory molecule, FasL. The results suggest that FasL is a prevalent mediator of immune privilege in stomach cancer.