SPEAR is out of place as Ledingham et al themin the same paper that the respective roles of cefotaxime and of intestinal decontamination "have still to be determined."" My comment on the danger of the systemic component stems from the ability of third generation cephalosporins to stimulate ji lactamases in the bacterial genera that are not uncommon in intensive therapy units. Mv main contention is that further evidence is required of the need for the systemic component, in view of the lack of studies defining its effect, as well as of the respective roles of oropharyngeal and gastrointestinal decontamination and of gastric acidity.
selves say
P J SANDERSON
Edgwarc General Hospital, Egware, MNiddlesex HAS ()AI) I Stotutenbeek CP, van Saenc HKF, Miranda DR, Zandstra DF, ILangrehr 1). 'I'he effect of oropharyngeal decontamination using topical non-absorbable antibiotics on the incidence of nosocomial respirators tract infections in multiple trauma patients. T'rauma 1987;27:357-64. 2 StouLtenbeek CI', van Saene HKF, Airanda DR, Zandstra DF. 'I'he cffect of- selective contamination of the digestive tract on colonisation and infection rate in multiple trauma patients. Intensive Care Med 1984;10:185-92. 3 lttcrtl K, Ruckdeschel G, Selbmann HK, et al. Prevention of colonisation and respiratory infections itt long-term ventilated patients by local antimnicrobial prophvlaxis. Intensive Care Med 1987;13: 106-13. 4 Kerver AJH, Romimes JH, Mevissen-Verhage EAE, et al. IPreventioni of colonisation and infection in critically ill patients: a prospective randomised sttudv. Croi C are Aied 1988;16: 1087-93. 5 Lcdingham IM, Alcock SR, Eastway Al, McDonald JC, MacKay IC, Ramsav (S. Triple regimen of selective decontamination of the digestive tract, ss stemic afotaxime, and microbiological survcillance for prsccntion of' acquired inifiection in intcnsive care. I.ancet 1988;i:785-90.
SIR,-In his comprehensive editorial Dr P J Sanderson proposes that autoinfection or endogenous infection is of considerable importance in intensive care.' Selective decontamination of the gastrointestinal tract is an attractive concept in this context and achieves one objective endpoint in the reduction of infection. The ultimate endpoint of reduction in mortality, however, remains unproved. This may be due to a number of reasons, which may include superinfection with resistant organisms, antibiotic or drug toxicity, and failure of the original theory behind decontamination in that "selective contamination" of the digestive tract may occur. Lactulose might be considered for use in these circumstances. It is associated with favourable alteration of the faecal flora, with additional considerable use in managing shigellosis and salmonellosis 4; possible reduction in the incidence ofurinary tract infectionsI and possibly respiratory tract infections' with regular treatment (prospective evaluation is in progress); and a proved antiendotoxin action. Lactulose is a synthetic sugar with osmotic laxative properties; it is well tolerated and has few adverse effects. In particular, it is not known to be associated with the overgrowth of any resistant organisms. Lactulose therefore may be an adjunct to controlling infection in neutropenic patients and in intensive care. 6
JAMES D FULTON DEBORAH J MACK Stohhill General Hospital, (ilasgow G21 3UW
Sattderson PJ. Selective decontamination of the digestive tract. Br MedJ 1989;299:1413-4. (2 December.) 2 Hofftnan K, Birchcr J. Vcranderungen der bakteriellen Darmhesiedlhtng nach Lactulosegaben. Schtweiz Med Wochensch I
7 Liehr H, Englisch G, Rasenack U. Lactulose-a drug with antiendotoxin effect. Hepatogastroenterology 1980;27:356-60. Plain JA, Bailey ME. Experimental and clinical study of lactulose in obstructive jaundice. Br7 Surg 1986;73:775-8.
The cyclotron saga continues SIR,-Dr Thelma D Bates states that morbidity from high energy neutrons is not excessive.' In support of this statement she cites a paper by Griffin et al,2 who analysed treatment complications from data obtained from the Radiation Therapy and Oncology Group's heavy particle registry. In all, 330 patients had been treated with neutrons for head and neck cancer. Neutrons, according to the protagonists of this treatment, are superior to x rays in treating tumours in these sites, in particular paranasal sinus and parotid gland tumours; so it is relevant to look at morbidity in this group of patients. Severe late effects were defined as grade 4 (life threatening) or grade 5 (fatal) according to the normal tissue late effect scoring scale of the Radiation Therapy and Oncology Group and European Organisation into Research on Cancer. On this rating 9% of patients treated with high energy neutrons suffered severe late effects compared with 20% of those treated with low energy neutrons. Thus the use of high energy neutrons seemingly halves the incidence of serious late complications, though Catterall stated that the reduction was 30%.' It is doubtful, even if we take the lower figure of 9%, whether a rate of serious late complications of this magnitude would be generally regarded as acceptable; nor is it fair to say, as Dr Bates does, that it is similar to that seen with modern megavoltage x ray therapy.' Of the various issues involved in the controversy about neutron treatment that of morbidity is perhaps the most important and the one to which the Department of Health should pay most attention. All of those who are interested are anxious to hear what is happening at Clatterbridge Hospital. It may be many years before meaningful results on the efficacy of treatment are available; any differences between neutron and photon treatment are likely to be marginal, so large numbers of patients will have to be treated and it is to be hoped that the mistake made at Hammersmith Hospital of using "tumour control" rather than survival as an end point will not be repeated. Morbidity, however, should be easier to assess. The high morbidity in the patients treated with neutrons for head and neck cancer at Hammersmith Hospital was found by analysing 95 patients in this group.4 The studies at Clatterbridge Hospital were started in 1986, and Errington reported a year ago that 165 patients had been treated with neutrons.5 I hope that data on morbidity will be published soon.
large sums of public money for the project. These anxieties were largely based on the fear of dangerous and possibly fatal complications from neutron therapy, coupled with only minimal evidence of improved tumour control or better survival than with conventional treatment. On the BBC Radio programme Face the Facts, which I quoted, Dr Mary Catterall pointed out that high energy neutron therapy should lead to a 30% reduction in treatment complications. However, it has become increasingly clear that even a reduction of this magnitude would be insufficient to produce acceptable morbidity, bearing in mind the extremely severe complications already encountered. Even a 50% reduction in morbidity would still leave substantial numbers of cases in which severe life threatening or fatal complications would be expected, and this is reflected in the overall incidence of complications documented in the paper quoted by Dr Bates herself.' In this study pooled results in neutron treated patients with head and neck cancer confirmed that "the late normal tissue severe toxicity (life threatening and fatal) rates in the head and neck were 9% for high energy accelerators and 20% for low energy acclerators." A further review of normal tissue complications following high energy neutron beam therapy was published last year.4 In this large study of 617 patients who had survived two years or more the overall "complication rate" was 18%. Only severe side effects were counted, including "severe fibrosis, persistent ulceration (not associated with the tumour site), necrosis of bone or soft tissue, or significant functional impairment." This degree of normal tissue damage would be unacceptable in conventional radiotherapy practice, so it seems premature to claim that toxicity of high energy neutron therapy is about equivalent to that of conventional photon treatment. One further anxiety about the provision of a new neutron facility in London concerns the difficulty of undertaking adequate controlled trials of the type that Dr Bates clearly feels to be necessary. Recruitment into the Clatterbridge studies has been difficult yet in London there are far more
competing radiotherapy centres. Scientifically reliable studies will doubtless prove especially difficult since the united opposition of the major cancer funding agencies has been so widely publicised. A recent review of particle radiation therapy research stated, "After great expenditures of effort, time and money, the favourable results of particle radiation therapy research have been modest and consequently disappointing to many."' In the context of extreme financial constraints within the health service, and inadequate cancer facilities within many health regions, the Department of Health's £6m gift could have been far better spent elsewhere.
A W G GOOLDEN
Aldenham, Hertfordshire WD2 8DL 1 Bates 'I'D. The cyclotron saga continues. BrMed3' 1990;300:46. (6 January.) 2 (;riffin TW, Pajak T, Laramore G, Davis I. Analysis of neutron therapy complications. Bull Cancer (Paris) 1986;73:582-6. 3 Catterall M. Radiotherapy's second setback. BrMed3' 1989;298: 384. (11 February.) 4 Medical Research Council. Neutron Therapy Working Group. A comparative review of the Hammersmith (1971-75) and Edinburgh (1977-82) neutron therapy trials of certain cancers of the oral cavity, oropharynx, larynx, and hypopharynx.
Br] Radisol 1986;59:429-40.
5 Errington RD. Radiotherapy's second setback. Br Med J
1989;298:384. (11 February.)
J S TOBIAS
Department of Radiotherapy and Oncology, University College Hospital, London WC 1E 6AU 1 Bates TD. The cyclotron saga continues. Br Med J 1990;300: 46-7. (6 January.) 2 Tobias JS. The cyclotron saga continues. Br Med J 1989;299: 1294-5. (25 November.) 3 Griffin T, Pajak T, Laramore G, Davis L. Analysis of neutron
radiotherapy treatment complications. Bull Cancer (Paris) 1986;73:582-6. 4 Cohen L, Schultheiss TE, Hendrickson FR, Mansell J, Saroia KR, Lennox A. Normal tissue reactions and complications following high-energy neutron beam therapy: 1. Crude response rates. IntJ Radiol Oncol Biol Phys 1989;16:73-8. 5 Parker RG. An appraisal of particle radiation therapy research. IntzJ Radiat Oncol Biol Phys 1988;15: 1435-9.
1 969;99:608.
3 Levine MM119, Hornick RB. Lactulose therapy in Shigella carrier state and acute dysentery. Intimicrob Agents Chemother 1975; 8:58 1-4. 4 Knothe H. 'I'herapy for Salmonella carriers. Umzveltmedizin
1980;2:25-7. 5
MIcCutcheon J, Fulton JI). Lowered prevalence of infection with
lactulose therapy in patients in continuing hospital care. 7 Hosp Infect 1989;13:81-6. 6 I;ulton JD. Infection limitation with lactulose therapy.journal ot Chlitical and Experimental (;erontiologv 1988- 1989;10: 117-24.
192
SIR,-Dr Thelma Bates complained' that my leading article2 had "deliberately confused the issue," though readers will recall that a careful review of the data led representatives of the Cancer Research Campaign, Medical Research Council, and other well informed bodies to urge the Department of Health to think again before providing
SIR,-In his editorial Dr J S Tobias' discusses the British government's decision to grant the Cyclotron Trust £6m towards the installation of a cyclotron at St Thomas's Hospital. The controversy resulting from this decision has resulted in some severe criticism of the efficacy of
BMJ VOLUME 300
20 JANUARY 1990
selves say
P J SANDERSON
Edgwarc General Hospital, Egware, MNiddlesex HAS ()AI) I Stotutenbeek CP, van Saenc HKF, Miranda DR, Zandstra DF, ILangrehr 1). 'I'he effect of oropharyngeal decontamination using topical non-absorbable antibiotics on the incidence of nosocomial respirators tract infections in multiple trauma patients. T'rauma 1987;27:357-64. 2 StouLtenbeek CI', van Saene HKF, Airanda DR, Zandstra DF. 'I'he cffect of- selective contamination of the digestive tract on colonisation and infection rate in multiple trauma patients. Intensive Care Med 1984;10:185-92. 3 lttcrtl K, Ruckdeschel G, Selbmann HK, et al. Prevention of colonisation and respiratory infections itt long-term ventilated patients by local antimnicrobial prophvlaxis. Intensive Care Med 1987;13: 106-13. 4 Kerver AJH, Romimes JH, Mevissen-Verhage EAE, et al. IPreventioni of colonisation and infection in critically ill patients: a prospective randomised sttudv. Croi C are Aied 1988;16: 1087-93. 5 Lcdingham IM, Alcock SR, Eastway Al, McDonald JC, MacKay IC, Ramsav (S. Triple regimen of selective decontamination of the digestive tract, ss stemic afotaxime, and microbiological survcillance for prsccntion of' acquired inifiection in intcnsive care. I.ancet 1988;i:785-90.
SIR,-In his comprehensive editorial Dr P J Sanderson proposes that autoinfection or endogenous infection is of considerable importance in intensive care.' Selective decontamination of the gastrointestinal tract is an attractive concept in this context and achieves one objective endpoint in the reduction of infection. The ultimate endpoint of reduction in mortality, however, remains unproved. This may be due to a number of reasons, which may include superinfection with resistant organisms, antibiotic or drug toxicity, and failure of the original theory behind decontamination in that "selective contamination" of the digestive tract may occur. Lactulose might be considered for use in these circumstances. It is associated with favourable alteration of the faecal flora, with additional considerable use in managing shigellosis and salmonellosis 4; possible reduction in the incidence ofurinary tract infectionsI and possibly respiratory tract infections' with regular treatment (prospective evaluation is in progress); and a proved antiendotoxin action. Lactulose is a synthetic sugar with osmotic laxative properties; it is well tolerated and has few adverse effects. In particular, it is not known to be associated with the overgrowth of any resistant organisms. Lactulose therefore may be an adjunct to controlling infection in neutropenic patients and in intensive care. 6
JAMES D FULTON DEBORAH J MACK Stohhill General Hospital, (ilasgow G21 3UW
Sattderson PJ. Selective decontamination of the digestive tract. Br MedJ 1989;299:1413-4. (2 December.) 2 Hofftnan K, Birchcr J. Vcranderungen der bakteriellen Darmhesiedlhtng nach Lactulosegaben. Schtweiz Med Wochensch I
7 Liehr H, Englisch G, Rasenack U. Lactulose-a drug with antiendotoxin effect. Hepatogastroenterology 1980;27:356-60. Plain JA, Bailey ME. Experimental and clinical study of lactulose in obstructive jaundice. Br7 Surg 1986;73:775-8.
The cyclotron saga continues SIR,-Dr Thelma D Bates states that morbidity from high energy neutrons is not excessive.' In support of this statement she cites a paper by Griffin et al,2 who analysed treatment complications from data obtained from the Radiation Therapy and Oncology Group's heavy particle registry. In all, 330 patients had been treated with neutrons for head and neck cancer. Neutrons, according to the protagonists of this treatment, are superior to x rays in treating tumours in these sites, in particular paranasal sinus and parotid gland tumours; so it is relevant to look at morbidity in this group of patients. Severe late effects were defined as grade 4 (life threatening) or grade 5 (fatal) according to the normal tissue late effect scoring scale of the Radiation Therapy and Oncology Group and European Organisation into Research on Cancer. On this rating 9% of patients treated with high energy neutrons suffered severe late effects compared with 20% of those treated with low energy neutrons. Thus the use of high energy neutrons seemingly halves the incidence of serious late complications, though Catterall stated that the reduction was 30%.' It is doubtful, even if we take the lower figure of 9%, whether a rate of serious late complications of this magnitude would be generally regarded as acceptable; nor is it fair to say, as Dr Bates does, that it is similar to that seen with modern megavoltage x ray therapy.' Of the various issues involved in the controversy about neutron treatment that of morbidity is perhaps the most important and the one to which the Department of Health should pay most attention. All of those who are interested are anxious to hear what is happening at Clatterbridge Hospital. It may be many years before meaningful results on the efficacy of treatment are available; any differences between neutron and photon treatment are likely to be marginal, so large numbers of patients will have to be treated and it is to be hoped that the mistake made at Hammersmith Hospital of using "tumour control" rather than survival as an end point will not be repeated. Morbidity, however, should be easier to assess. The high morbidity in the patients treated with neutrons for head and neck cancer at Hammersmith Hospital was found by analysing 95 patients in this group.4 The studies at Clatterbridge Hospital were started in 1986, and Errington reported a year ago that 165 patients had been treated with neutrons.5 I hope that data on morbidity will be published soon.
large sums of public money for the project. These anxieties were largely based on the fear of dangerous and possibly fatal complications from neutron therapy, coupled with only minimal evidence of improved tumour control or better survival than with conventional treatment. On the BBC Radio programme Face the Facts, which I quoted, Dr Mary Catterall pointed out that high energy neutron therapy should lead to a 30% reduction in treatment complications. However, it has become increasingly clear that even a reduction of this magnitude would be insufficient to produce acceptable morbidity, bearing in mind the extremely severe complications already encountered. Even a 50% reduction in morbidity would still leave substantial numbers of cases in which severe life threatening or fatal complications would be expected, and this is reflected in the overall incidence of complications documented in the paper quoted by Dr Bates herself.' In this study pooled results in neutron treated patients with head and neck cancer confirmed that "the late normal tissue severe toxicity (life threatening and fatal) rates in the head and neck were 9% for high energy accelerators and 20% for low energy acclerators." A further review of normal tissue complications following high energy neutron beam therapy was published last year.4 In this large study of 617 patients who had survived two years or more the overall "complication rate" was 18%. Only severe side effects were counted, including "severe fibrosis, persistent ulceration (not associated with the tumour site), necrosis of bone or soft tissue, or significant functional impairment." This degree of normal tissue damage would be unacceptable in conventional radiotherapy practice, so it seems premature to claim that toxicity of high energy neutron therapy is about equivalent to that of conventional photon treatment. One further anxiety about the provision of a new neutron facility in London concerns the difficulty of undertaking adequate controlled trials of the type that Dr Bates clearly feels to be necessary. Recruitment into the Clatterbridge studies has been difficult yet in London there are far more
competing radiotherapy centres. Scientifically reliable studies will doubtless prove especially difficult since the united opposition of the major cancer funding agencies has been so widely publicised. A recent review of particle radiation therapy research stated, "After great expenditures of effort, time and money, the favourable results of particle radiation therapy research have been modest and consequently disappointing to many."' In the context of extreme financial constraints within the health service, and inadequate cancer facilities within many health regions, the Department of Health's £6m gift could have been far better spent elsewhere.
A W G GOOLDEN
Aldenham, Hertfordshire WD2 8DL 1 Bates 'I'D. The cyclotron saga continues. BrMed3' 1990;300:46. (6 January.) 2 (;riffin TW, Pajak T, Laramore G, Davis I. Analysis of neutron therapy complications. Bull Cancer (Paris) 1986;73:582-6. 3 Catterall M. Radiotherapy's second setback. BrMed3' 1989;298: 384. (11 February.) 4 Medical Research Council. Neutron Therapy Working Group. A comparative review of the Hammersmith (1971-75) and Edinburgh (1977-82) neutron therapy trials of certain cancers of the oral cavity, oropharynx, larynx, and hypopharynx.
Br] Radisol 1986;59:429-40.
5 Errington RD. Radiotherapy's second setback. Br Med J
1989;298:384. (11 February.)
J S TOBIAS
Department of Radiotherapy and Oncology, University College Hospital, London WC 1E 6AU 1 Bates TD. The cyclotron saga continues. Br Med J 1990;300: 46-7. (6 January.) 2 Tobias JS. The cyclotron saga continues. Br Med J 1989;299: 1294-5. (25 November.) 3 Griffin T, Pajak T, Laramore G, Davis L. Analysis of neutron
radiotherapy treatment complications. Bull Cancer (Paris) 1986;73:582-6. 4 Cohen L, Schultheiss TE, Hendrickson FR, Mansell J, Saroia KR, Lennox A. Normal tissue reactions and complications following high-energy neutron beam therapy: 1. Crude response rates. IntJ Radiol Oncol Biol Phys 1989;16:73-8. 5 Parker RG. An appraisal of particle radiation therapy research. IntzJ Radiat Oncol Biol Phys 1988;15: 1435-9.
1 969;99:608.
3 Levine MM119, Hornick RB. Lactulose therapy in Shigella carrier state and acute dysentery. Intimicrob Agents Chemother 1975; 8:58 1-4. 4 Knothe H. 'I'herapy for Salmonella carriers. Umzveltmedizin
1980;2:25-7. 5
MIcCutcheon J, Fulton JI). Lowered prevalence of infection with
lactulose therapy in patients in continuing hospital care. 7 Hosp Infect 1989;13:81-6. 6 I;ulton JD. Infection limitation with lactulose therapy.journal ot Chlitical and Experimental (;erontiologv 1988- 1989;10: 117-24.
192
SIR,-Dr Thelma Bates complained' that my leading article2 had "deliberately confused the issue," though readers will recall that a careful review of the data led representatives of the Cancer Research Campaign, Medical Research Council, and other well informed bodies to urge the Department of Health to think again before providing
SIR,-In his editorial Dr J S Tobias' discusses the British government's decision to grant the Cyclotron Trust £6m towards the installation of a cyclotron at St Thomas's Hospital. The controversy resulting from this decision has resulted in some severe criticism of the efficacy of
BMJ VOLUME 300
20 JANUARY 1990
