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J D Harrison

Publications and source records attributed to J D Harrison.

At least 19 recordsLinked to original sources
PubMed2003

Quantitative comparisons of cancer induction in humans by internally deposited radionuclides and external radiation.

PURPOSE: To compare quantitative estimates of lifetime cancer risk in humans for exposures to internally deposited radionuclides and external radiation. To assess the possibility that risks from radionuclide exposures may be underestimated. MATERIALS AND METHODS: Risk estimates following internal exposures can be made for a small number of alpha-particle-emitting nuclides. (1) Lung cancer in underground miners exposed by inhalation to radon-222 gas and its short-lived progeny. Studies of residential (222)Rn exposure are generally consistent with predictions from the miner studies. (2) Liver cancer and leukaemia in patients given intravascular injections of Thorotrast, a thorium-232 oxide preparation that concentrates in liver, spleen and bone marrow. (3) Bone cancer in patients given injections of radium-224, and in workers exposed occupationally to (226)Ra and (228)Ra, mainly by ingestion. (4) Lung cancer in Mayak workers exposed to plutonium-239, mainly by inhalation. Liver and bone cancers were also seen, but the dosimetry is not yet sufficiently good enough to provide quantitative estimates of risks. Comparisons can be made between risk estimates for radiation-induced cancer derived for radionuclide exposure and those derived for the A-bomb survivors, exposed mainly to low-LET (linear energy transfer) external radiation. Data from animal studies, using dogs and rodents, allow comparisons of cancer induction by a range of alpha- and beta-/gamma-emitting radionuclides. They provide information on relative biological effectiveness (RBE), dose-response relationships, dose-rate effects and the location of target cells for different malignancies. RESULTS: For lung and liver cancer, the estimated values of risk per Sv for internal exposure, assuming an RBE for alpha-particles of 20, are reasonably consistent with estimates for external exposure to low-LET radiation. This also applies to bone cancer when risk is calculated on the basis of average bone dose, but consideration of dose to target cells on bone surfaces suggests a low RBE for alpha-particles. Similarly, for leukaemia, the comparison of risks from alpha-irradiation ((232)Th and progeny) and external radiation suggest a low alpha RBE; this conclusion is supported by animal data. Risk estimates for internal exposure are dependent on the assumptions made in calculating dose. Account is taken of the distribution of radionuclides within tissues and the distribution of target cells for cancer induction. For the lungs and liver, the available human and animal data provide support for current assumptions. However, for bone cancer and leukaemia, it may be that changes are required. Bone cancer risk may be best assessed by calculating dose to a 50 micro m layer of marrow adjacent to endosteal (inner) bone surfaces rather than to a single 10 micro m cell layer as currently assumed. Target cells for leukaemia may be concentrated towards the centre of marrow cavities so that the risk of leukaemia from bone-seeking radionuclides, particularly alpha emitters, may be overestimated by the current assumption of uniform distribution of target cells throughout red bone marrow. CONCLUSIONS: The lifetime risk estimates considered here for exposure to internally deposited radionuclides and to external radiation are subject to uncertainties, arising from the dosimetric assumptions made, from the quality of cancer incidence and mortality data and from aspects of risk modelling; including variations in baseline rates between populations for some cancer types. Bearing in mind such uncertainties, comparisons of risk estimates for internal emitters and external radiation show good agreement for lung and liver cancers. For leukaemia, the available data suggest that the assumption of an alpha-particle RBE of 20 can result in overestimates of risk. For bone cancer, it also appears that current assumptions will overestimate risks from alpha-particle-emitting nuclides, particularly at low doses.

Animals↗
PubMed2002

The placental transfer of cerium: experimental studies and estimates of doses to the human fetus from 141Ce and 144Ce.

PURPOSE: To measure the transfer of cerium from mother to fetus in experimental animals and estimate doses to the human fetus following intakes of radioisotopes of Ce. MATERIALS AND METHODS: Cerium-141 in chloride solution was administered intravenously to rats at different stages of pregnancy (days 9.5, 12.5 or 18.5), and retention in the embryo/fetus and associated tissues was measured 3 days later in each case. Retention in rat fetal tissues on day 21.5 (shortly before birth) was also measured after administration of 141Ce chloride 1 month prior to conception or 141Ce citrate on day 18.5. Cerium-141 chloride was administered to guinea pigs on day 50 for measurements of fetal retention on day 57 (shortly before birth). RESULTS: Retention of 141Ce in the rat embryo/fetus, measured at 3 days after administration to the mother, increased from about 0.00002% of injected activity per embryo/fetus on day 12.5 to about 0.014% on day 21.5 of gestation. However, the relative concentrations of 141Ce in the embryo/fetus and mother (CF:CM ratio) were between 0.005 and 0.01 in each case. After 141Ce administration prior to conception, retention by the rat fetus on day 21.5 was substantially lower than after short-term administration. Comparison of retention of 141Ce on day 21.5 after administration on day 18.5 as either chloride or citrate showed similar levels in maternal tissues but greater transfer to the fetus (CF:CM ratio of 0.03). Retention in the guinea pig fetus in late gestation at 7 days after administration of (141)Ce chloride was about 0.05% injected activity per fetus, corresponding to a CF:CM ratio of about 0.02. CONCLUSION: These results and other published animal data have been used to specify CF:CM ratios for use in the calculation of doses to the human fetus. The values used were 0.05 for intakes during pregnancy and 0.01 for intakes prior to conception. Doses to the offspring after maternal ingestion of 141Ce or 144Ce are largely due to irradiation from activity in the maternal colon and are insensitive to CF:CM. After inhalation, however, absorption of Ce to blood is much greater and doses to the offspring are dominated by the contribution from activity in the fetus, and therefore dependent on the CF:CM ratio used.

Animals↗
PubMed2002

Dose coefficients for the embryo and foetus following intakes of radionuclides by the mother.

Committee 2 of the International Commission on Radiological Protection (ICRP) has the responsibility for calculating radiation doses from intakes of radionuclides for all age groups in the population. Publication 88 of the ICRP, which has recently been published, describes the development of models used for calculating radiation doses to the embryo and foetus following intakes of radionuclides by the mother. It also gives radiation doses to the offspring for intakes of radionuclides by the mother either before or during pregnancy. The approaches used in the development of the biokinetic and dosimetric models are summarised here together with a comparison of the doses to the offspring with those to the reference adult.

Adult↗
PubMed2002

Uncertainties in dose coefficients for intakes of tritiated water and organically bound forms of tritium by members of the public.

The International Commission on Radiological Protection (ICRP) provides models for the calculation of doses from intakes of radionuclides, including intakes of tritium as tritiated water (HTO) or organically bound tritium (OBT). The ICRP models for HTO and OBT are explained and the assumptions made are examined. The reliability of dose estimates is assessed in terms of uncertainties in central estimates for population groups. The models consider intakes of HTO and OBT by ingestion and inhalation by adults and children and doses to the fetus following intakes by the mother. The analysis includes uncertainties in the absorption of OBT to blood, incorporation of tritium into OBT in body tissues, retention times in tissues, transfer to the fetus and the relative biological effectiveness (RBE) of tritium beta emissions compared with gamma rays. Heterogeneity of dose within tissues and cells is also considered. For intakes as HTO, dose is predominantly due to distribution and retention of HTO in body water and it was concluded that adult doses are reliable to within a factor of 2. For intakes of OBT, the extent of incorporation into OBT in body tissues results in greater uncertainties with estimates relying on animal data for selected compounds. The analysis indicated that adult doses from OBT can be considered to be known to within a factor of 3. Greater uncertainties in estimated doses for children and for in utero exposures were considered. Central values from the uncertainty analyses of doses for HTO and OBT were greater than the corresponding ICRP dose coefficients by about a factor of 2, mainly due to the inclusion of uncertainties in RBE for tritium. A detailed assessment of doses using appropriate parameters and considering uncertainties would be of particular importance in situations where the dose may approach dose limits or constraints. For exposures to known forms of OBT, specific dose assessments may be required.

Adult↗
PubMed2001

Variation in the response to ductal obstruction of feline submandibular and sublingual salivary glands and the importance of the innervation.

A variable response following ductal ligation of feline salivary glands corresponds to the human condition but contrasts with a predictable atrophy in obstructed salivary glands of rodents popularly used as a model for human salivary problems. The present investigation is concerned with a possible reason for the variable response, namely the preservation of the innervation. Ducts of feline submandibular and sublingual salivary glands were ligated with or without the inclusion of the chorda tympani. Inclusion led to a delayed initial response followed by progressive atrophy until the parenchyma was extremely atrophic, whereas avoidance of the chorda led to the variable response in which variable numbers of acini of a similar form to normal persisted. The results establish the atrophic effect of inclusion of the chorda tympani in ductal ligation and indicate the caution that should be exercised in the extrapolation of the rodent model to the human condition.

Animals↗
PubMed2001

Tumorigenic target cell regions in bone marrow studied by localized dosimetry of 239Pu, 241Am and 233U in the mouse femur.

PURPOSE: To study the temporal change in microdistribution of plutonium-239, americium-241 and uranium-233 in the mouse distal femur and to compare and combine calculated radiation doses with those obtained previously for the femoral shaft. Also, to relate doses to relative risks of osteosarcoma and acute myeloid leukaemia. MATERIALS AND METHODS: Computer-based image analysis of neutron-induced and alpha-track autoradiographs of sections of mouse femora was used to quantify the microdistribution of (239)Pu, (241)Am and (233)U from 1 to 448 days after intraperitoneal injection. Localized dose-rates and cumulative doses over this period were calculated for different regions of the marrow spaces in trabecular bone. The results were then combined with previous data for doses to the cortical marrow of the femoral shaft. A morphometric analysis of the distal femur was carried out. RESULTS: Initial deposition on endosteal surfaces and dose-rates near to the trabecular surfaces at 1 day were two to four times greater than corresponding results for cortical bone. Burial was most rapid for (233)U, about twice the rate in cortical bone. As in cortical bone, subsequent uptake into the marrow was seen for (239)Pu and (241)Am but not (233)U. Cumulative doses to 448 days for different regions of trabecular marrow were greater than corresponding values for cortical marrow for each radionuclide. Combined doses reflected the greater overall volume of cortical marrow. CONCLUSIONS: Cumulative radiation doses to the 10 microm thick band of marrow adjacent to all endosteal surfaces were in the ratio of approximately 7:3:1 for (239)Pu:(241)Am:(233)U. This ratio is not inconsistent with observed incidences of osteosarcoma induction by the three nuclides. Analysis of doses to different depths of marrow, however, showed that although ratios were probably not significantly different to that for a 10 microm depth, better correlations with osteosarcomagenic risk were obtained with 20-40 microm depths. For acute myeloid leukaemia, the closest relationship between relative risk and doses was obtained by considering only the central 5-10% of marrow, which gave a dose ratio of approximately 12:11:1 for (239)Pu:(241)Am:(233)U respectively.

Americium↗
PubMed2001

In utero haemopoietic sensitivity to alpha, beta or X-irradiation in CBA/H mice.

PURPOSE: To assess in utero sensitivity to x-rays, alpha-emissions from plutonium-239 and beta-emissions from tritium in terms of induction of chromosomal aberrations in bone marrow cells. MATERIALS AND METHODS: CBA/H mice were exposed to a single dose of X-rays (0.5Gy) on either day 7 or day 14 of pregnancy or given (239)Pu (100 kBq kg(-1)) by intraperitoneal injection on either day 6 or day 13. Tritium was administered to mice throughout pregnancy as either tritiated water, ad libitum in drinking water (total intake averaged 130 MBq), or as homogenized tritiated cress, administered by gastric intubation (total 60 MBq). Irradiated and unexposed control mice and their offspring were sacrificed at 2-8 weeks after birth. Direct metaphase preparations from femoral bone marrow cells from mothers and offspring were used for G-band analysis. RESULTS: The incidence of stable aberrations was significantly and similarly increased in neonatal and maternal marrow samples after exposure to X-rays, (239)Pu or (3)H. The estimated average bone absorbed doses from (239)Pu in pregnant females were similar to the X-ray dose of 0.5 Gy, suggesting a low RBE for alpha-irradiation in adults. The similar levels of damage observed in neonates after X-irradiation and 239Pu exposure are indicative of greater in utero sensitivity to alpha-irradiation since the overall estimated in utero alpha-particle doses to haemopoietic tissue were much lower. In utero doses from (3)H and corresponding maternal doses were around 0.5Gy, showing no evidence of greater in utero sensitivity, no significant difference between the effects of the two forms of tritium, and were consistent with an RBE value of 1-2. CONCLUSIONS: Comparison of stable aberration yields in haemopoietic cells suggests a greater sensitivity to alpha-particles from (239)Pu than X-rays or beta-particles from (3)H for irradiation in utero but a low RBE value in adults.

Age Factors↗
PubMed2001

Induction of osteosarcoma and acute myeloid leukaemia in CBA/H mice by the alpha-emitting nuclides, uranium-233, plutonium-239 and amercium-241.

PURPOSE: To compare tumour induction in CBA/H mice, principally osteosarcoma and acute myeloid leukaemia, resulting from exposure to the alpha-emitting nuclides, uranium-233, plutonium-239 and americium-241, and to relate differences between the three nuclides to the pattern of dose delivery within tissues. MATERIALS AND METHODS: Each nuclide was administered intraperitoneally in citrate solution to three groups of adult male CBA/H mice at levels of activity which gave estimated life-time average skeletal doses of about 0.25-0.3 Gy, 0.5-1 Gy and 1-2 Gy. Animals were carefully monitored and sacrificed as soon as they showed signs of ill health; tumours were identified by standard histopathological techniques. RESULTS: Statistical modelling by Cox regression showed that, considering all three nuclides together, there was a highly significant increase in risk of death from osteosarcoma or myeloid leukaemia with increasing dose rate. For osteosarcoma, the effect was significantly greater for 239Pu than 241Am, while separate analysis for 233U showed no significant increase with increasing dose rate. For example, the increase in relative risk of death from osteosarcoma for an increase in life-time average dose rate to bone of 1 mGyd(-1) was 4.2 (2.7-6.5) for 239Pu, 2.3 (1.4-3.4) for 241Am and 1.1 (0.4-3.1) for 233U. For myeloid leukaemia, there was no significant difference between 239Pu and 241Am in the effect of dose rate. The increase in relative risk from myeloid leukaemia for an increase in average dose rate of 1 mGyd(-1) was 1.8 (1.1-2.8) for 239Pu, 2.0 (1.4-2.9) for 241Am and 1.5 (0.8-2.7) for 233U. Significant increases in renal and hepatic carcinomas were also recorded in animals exposed to 233U and 241Am, respectively. Studies of the distribution of the nuclides within the skeleton, published separately, have shown differences in their retention in individual bones and within bone. The proportions of decays occurring near to endosteal bone surfaces and throughout bone marrow were in the order: 239Pu> 241Am>233U. CONCLUSIONS: For osteosarcoma, the relative effectiveness of the nuclides in terms of average bone dose, in the order 239Pu>241Am>233U, is consistent with the proportion of dose delivered near to endosteal surfaces. For myeloid leukaemia, the greater effectiveness of 239Pu and 241Am than 233U is consistent with their accumulation in marrow.

Americium↗
PubMed2001

Reliability of the ICRP's dose coefficients for members of the public, II. Uncertainties in the absorption of ingested radionuclides and the effect on dose estimates. International Comission on Radiological Protection.

Data on the gastrointestinal absorption of 12 elements have been reviewed. In each case, absorption is expressed as the fraction of the ingested element absorbed to blood, referred to as the f1 value, applying to intakes of unspecified chemical form by average population groups. The level of confidence in individual absorption values has been estimated in terms of lower and upper bounds, A and B, such that there is judged to be roughly a 90% probability that the true central value is no less than A and no greater than B. Ranges are proposed for intakes by adults, 10-year-old children and 3-month-old infants. Uncertainty in f1 values (B/A) ranged from 10% to factors of 100-400. The lowest uncertainties were for the well absorbed elements, H, I and Cs, for which there are good data, and the greatest uncertainties were for less well absorbed elements for which few data are available, particularly Zr and Sb. Ranges were generally wider for children and infants than for adults because of the need to allow for the likelihood of increased absorption with only limited data in support of the proposed values. The largest ranges were for 3-month-old infants, reflective lack of knowledge on the time-course and magnitude of possible increased absorption in the first few months of life. For each age group, ICRP values of absorption tend towards the upper bound of the ranges, indicating a degree of conservatism in th calculation of ingestion dose coefficients. Examination of the effect of the proposed confidence intervals for f1 values on uncertainties in dose coefficients for ingested radionuclides showed that there was no direct relationship. For some radionuclides, uncertainties in effective dose were small despite large uncertainties in f1 values while for others the uncertainties in effective doses approached the corresponding values for uncertainty in f1 values. These differences reflect the relative contributions to effective dose from cumulative activity in the contents of the alimentary tract, which in many cases is insensitive to uncertainties in f1, and cumulative activity of the absorbed radionuclide in systemic tissues, which is proportional to f1. In general, uncertainties in effective close for children and infants exceeded those in adults as a result of greater uncertainties in f1 values for the younger age groups. However, this effect was reduced in some cases by shorter retention times of absorbed nuclides in body tissues and organs.

Adult↗
PubMed2001

A model for the transfer of alkaline earth elements to the fetus.

A biokinetic model has been developed for the transfer of calcium, strontium, barium and radium to the human fetus. For the mother, ICRP models were adapted for pregnancy to include increases in gastrointestinal absorption, urinary excretion and bone turnover rates. The fetus was modelled with blood, soft tissue and bone compartments. Fetal requirements for Ca were determined by skeletal calcification, and recyling between fetal and maternal blood was inlcluded. Daily transfer of Sr, Ba and Ra to the fetus was taken to be lower than for Ca by factors of 0.6 for Sr and 0.4 for Ba and Ra. For acute intakes in late pregnancy at 35 weeks after conception, when maximum transfer occurs, the model predicts whole-body fetus:mother concentration ratios (C(F):C(M)) of 18 for Ca, 8 for Sr and 2 for Ba and Ra, respectively. Estimates of committed equivalent doses to the red bone marrow of offspring, including in utero and postnatal dose, after maternal ingestion in late pregnancy, were greater than corresponding doses in adults by factors of 20-31 for 45Ca, 2-3 for 90Sr and 3-4 for 226Ra but slightly lower (0.8-1.9) for 133Ba.

Barium↗
PubMed2001

Lack of detectable transmissible chromosomal instability after in vivo or in vitro exposure of mouse bone marrow cells to 224Ra alpha particles.

Several studies over recent years have highlighted the possibility that radiation can induce transmissible genomic instability. Most of these involve in vitro irradiation and usually in vitro culture. Here it is reported that the short-half-life bone-seeking alpha-particle emitter (224)Ra did not induce excess transmissible chromosomal instability in CBA/H mouse bone marrow cells in a 100-day period after in vivo or in vitro exposure. Similarly, no excess transmissible chromosomal instability could be detected after in vivo whole-body X irradiation. It was noted, however, that short-term culture of murine bone marrow cells elevated yields of aberrations, as did transplantation of untreated marrow into radiation-ablated hosts. These findings emphasize the sensitivity of murine hemopoietic tissue to experimental manipulation and reinforce the importance of appropriate concurrent control experiments in any investigation of transmissible genomic instability.

Alpha Particles↗
PubMed2000

The effects of ductal obstruction on the acinar cells of the parotid of cat.

Twenty-nine parotids ligated for between 1 and 365 days were examined by light and electron microscopy. Major changes in the acini were seen at 4 days and included vacuolation, disintegration, extravasation, apoptosis, phagy and a reduction in number and size of secretory granules. There was a further reduction in secretory granules from 7 to 12 days, but acinar cells persisted even up to 365 days, some contained a luminal concentration of small secretory granules and occasionally acinar cells of a similar appearance to normal were found. These findings contrast with a reported absence of acinar cells from the obstructed parotid of rat and show that parotid acinar cells are able to persist and retain an appearance indicative of secretory activity.

Animals↗
PubMed2000

Microdistribution and localized dosimetry of the alpha-emitting radionuclides 239Pu, 241Am and 233U in mouse femoral shaft.

PURPOSE: To analyse the temporal change in microdistribution of 239Pu, 241Am and 233U in mouse femur and to compare the calculated radiation doses with regions of the bone marrow thought to contain target cells for osteosarcoma and leukaemia with relative risk for those diseases. MATERIALS AND METHODS: Neutron-induced and alpha-track autoradiographs were prepared from femora of the CBA/H mouse that had been injected with 40 kBq kg(-1) radionuclide between 1 and 448 days previously. Computer-based image analysis of the autoradiographs was performed and dosimetric methods applied to obtain radiation dose-rates to different regions of the marrow cavity. RESULTS: Initially each radionuclide deposited on endosteal and periosteal bone surfaces; 241Am was additionally deposited on vascular canal surfaces. Redistribution resulted in 233U being incorporated into bone, while 239Pu and 241Am showed transfer into both bone volume and marrow. Accumulation in the central marrow peaked at 112-224 days post-injection, but subsequently was cleared by 448 days. Cumulative doses to both osteosarcomagenic and myeloid leukaemogenic target cell regions showed the trend 239Pu > 241Am > 233U. CONCLUSIONS: Calculation of cumulative doses to a 10-microm layer of marrow adjacent to bone surfaces appears to be a suitable predictor for risk of osteosarcoma. Risks of myeloid leukaemia in the mouse are better predicted by considering the central marrow as the target region rather than average dose to all marrow.

Alpha Particles↗
PubMed2000

Comparison of cytogenetic damage in cultured cells from cobalt-60 gamma-radiation and the Auger emitter zinc-65.

PURPOSE: To assess the ability of the Auger-emitting nuclide, zinc-65 (65Zn), relative to gamma-irradiation, to cause chromosomal aberrations in cultured rat prostate cells. MATERIALS AND METHODS: Rat prostate adenocarcinoma cells in culture were exposed to doses of 1, 2, 3 or 5 Gy of external gamma-irradiation for 24h or incubated with 0.7, 1.5, 1.8 or 2.8 MBq of 65Zn for 24 h. The uptake by and clearance from cells of 65Zn was measured. Metaphase spreads prepared from washed cells were scored for chromatid- and chromosome-type aberrations. RESULTS: Following exposure to 65Zn or gamma-irradiation, chromatid-type damage was more commonly observed than chromosome-type aberrations. The relationship between induced chromatid damage and gamma dose (to 3 Gy) was best fitted by a second-order polynomial function, while the activity response relationship for chromatid damage caused by 65Zn appeared to be best fitted by a straight line. Measurements of the uptake of 65Zn by cells showed that average concentrations within cells were about 100 times the concentration in the culture medium. Assuming uniform distribution of 65Zn within cells, with 36% in the nucleus, the dose was estimated as 0.70 Gy per MBq added 65Zn, with Auger electrons contributing most (93%) of the dose. Assuming that 20% of cellular zinc was localized in the nucleus, based on previous measurements, the dose to the nucleus was calculated as 0.44 Gy per MBq added 65Zn. RBE values for chromatid damage induced by 65Zn compared to gamma-radiation range from about 1 to 3 based on a uniform dose throughout the cell and from about 2 to 5 based on 20% of 65Zn in the cell nucleus. CONCLUSION: The observed radiotoxicity of 65Zn is consistent with its behaviour as an Auger-emitting radionuclide that is localized to some extent in the nucleus.

Adenocarcinoma↗
PubMed1999

Energy storage and cytokine response in patients undergoing liver transplantation.

Overproduction of pro-inflammatory cytokines during surgery has been known to exert tissue-damaging and lethal effects on the host. Hypermetabolism-associated malnutrition, a common feature of patients with end-stage liver diseases, is related to the presence of a systemic inflammatory response, as reflected by enhanced levels of proinflammatory cytokines. The present study was designed to evaluate energy status of 29 liver transplant recipients, and to assess the relation of energy storage to post-operative cytokine response. The glycogen contents of the graft, and the recipient's abdominal muscle and old liver were measured. The plasma concentrations of tumour necrosis factor alpha, interleukin 1beta, interleukin 6, lactate, pyruvate and total ketone bodies were determined during and after surgery. In undernourished patients, ketone bodies seemed to be the major fuel available to muscle. The concentration of ketone bodies decreased rapidly after the incision, and remained at a low level after reperfusion. These patients had higher plasma levels of lactate/pyruvate ratio and aromatic amino acids during the anhepatic phase, followed by an exaggerated response of cytokines. Depletion of energy storage of the recipients may be involved in the deterioration of peri-operative energy metabolism and the exaggerated post-operative cytokine response.

Adolescent↗
PubMed1999

Phase II trial of radical surgery for locally advanced pelvic neoplasia.

BACKGROUND: Reported operative mortality and survival rates following total pelvic exenteration (TPE) for recurrent pelvic neoplasia are now as good as those for many primary treatments. The currently accepted primary treatments for these tumours are, however, still either radiotherapy alone or radiotherapy and chemotherapy. The primary aim of this study was to evaluate the safety and tolerability of TPE and secondarily to ascertain survival after TPE. METHODS: This was a phase II study of 50 patients with locally advanced pelvic tumours who underwent TPE. RESULTS: Thirty-two patients (64 per cent) underwent TPE for recurrent carcinoma of the cervix, seven (14 per cent) for rectal cancer, three (6 per cent) for vulval carcinoma, three (6 per cent) for vaginal carcinoma, two (4 per cent) for prostate cancer and three (6 per cent) for other tumours. The 30-day mortality rate was 8 per cent with an in-hospital mortality rate of 16 per cent. The crude morbidity rate was 62 per cent, with 23 patients (46 per cent) having grade III or IV toxicity. A complete response was achieved in 63 per cent and a partial response in 37 per cent of patients. The overall median survival time was 86 weeks; it was 111 weeks in patients in whom a complete response was achieved. CONCLUSION: The survival and operative mortality rates that are now attainable with TPE are comparable to those achieved with chemoradiotherapy in advanced pelvic neoplasia. TPE should no longer be reserved for salvage therapy and should perhaps be compared with chemoradiotherapy as first-line treatment in a phase III randomized trial in patients with these tumours.

Adult↗