311 CONTROLLED TRIALS IN SURGERY
Letters
to
the Editor
would argue with the logic of "controlled surgery" proposed by Professor Spodick and his colleagues.’ As a surgeon, I would be delighted to see such trials, but the major question is how shall they be done? For most procedures, this would require a multicentre approach with all its inherent problems. One only needs to examine the results of some completed trials to see the problems involved, even in
SIR,-No
one
trials in
IMMUNOSTIMULATION FOR CHRONIC ACTIVE HEPATITIS
SIR,-Although the pathogenesis of chronie active hepatitis (C.A.H.) is not fully understood the indications are that this devastating liver disease is mainly due to an impaired immune response, unable to eliminate liver cells infected with hepatitis control autoimmune reactions. If this hypothesis is why, instead of immunosuppression, not try to improve the patient’s immunity and help to eliminate viral infection and naturally suppress the clones of immune cells responsible for autoimmunity? We have tested this idea with B.c.G. vaccine, a potent, mostly cell-mediated, stimulator of the defence system. Twenty children with C.A.H. were selected (thirteen boys and five girls aged 3-15 years). Six children had previously been treated with steroids and azathioprine. The effect of B.c.G. vaccination was monitored by clinical observation, biochemistry, and histology, and immunity was investigated by skin tests with tuberculin and dinitrochlorobenzene. (D.N.C.B.). The children were vaccinated intradermally with B.c.G. vaccine (Poland strain) weekly, and with increasing volume of vaccine. The starting dose was 0.2 ml per injection; the final one was 1 ml for each multifocal injection. Every three subsequent injections were separated by an interval of 1 month, after which the patient was vaccinated again, with a larger dose up to 1 ml B.c.G. vaccine. The patients were given a total of 5.4 ml (0 - 27 mg dry mass of mycobacteria). The reactions to the injections consisted of local ones similar to those after smallpox vaccination, lasting up to 4 months and leaving a flat scar, and an influenza-like reaction (fever, chills, headache, muscle pains) lasting 1-4 days. The reactions were proportional to the dose of vaccine. The effect of B.c.G. vaccination was evaluated 1 year afterwards (see table).
virus
or
correct
INDICATORS OF C.A.H. AND IMMUNE FUNCTION IN 20 CHILDREN BEFORE AND AFTER COURSE OF B.C.G. INJECTIONS
*60-1000 Reitman-Frankel units. tHistology in the remaining 11 patients revealed 1 normal liver, 3 minimal hepatitis, and 7 with improvements. C.E.P.=Counterelectrophoresis. R.l.A.=radioimmunoassay.
The results indicate that B.C.G. vaccine stimulation in children with c.A.H. has therapeutic possibilities. The clinical improvement, return to normal liver function, and elimination of HBsAg (in several cases) are promising. In all children there was long-lasting clinical and biochemical improvement. The worst histology was observed in those who, before vaccine stimulation, had been treated by immunosuppression. Immunosuppression should be applied with circumspection in C.A.H., especially now that there is the alternative of B.C.G. stimulation. of Immunopathology, Institute of Infectious and Parasitic Diseases, Medical Academy in Warsaw, 01-201 Warsaw, Poland
WITOLD
Municipal Hospital for for Children, Warsaw
R. DEBSKI KRYSTYNA DERECKA
Department
Infectious Diseases
J. BRZOSKO
as
areas. For example, the University Group Diabetes Program and the multicentre trial on low-dose heparin have been the subject of bitter controversy. Where does the truth lie in these studies? It is unfortunate that Spodick et al. looked only in the surgical mirror when making their criticisms. A multicentre trial would probably work if it did not involve people-yes, scientists-who in the search for truth often tend to act in a way more human than scientific. One thing that has impressed me in working in new areas with new challenges is how very difficult it is to be completely honest. It is so easy to ignore, skip over, and leave out those parts of the puzzle which appear irrelevant, particularly if you start out with a bias to which your name is attached. How often have Spodick et al. seen a prominent physician, in writing or before an audience, say "I made a terrible mistake based upon a lousy experiment and bad data"? This is a rare happening. I have never seen it. I agree that we must urge continued scepticism for all new therapies and plead with those who toil in this area to employ good science and not worry about the publication filter, which in many cases is no better than the material which is submitted under the guise of science.
non-surgical
Department of Surgery, School of Medicine, University of Washington, Seattle, Washington 98195, U.S.A.
D. E. STRANDNESS
TRAINING FOR SURGERY
SIR,-We were interested in your editorial on surgical train-
ing (July 8, p. 82). We agree that training, examination,
and assessment should be differentiated. However, we must take issue with the suggestion that no thought has been given to these problems in surgery outside the Edinburgh College. The advent and establishment of higher surgical training during the past six years represents a major advance in the final preparation of a surgeon for his consultant job. It has been achieved in a short time and by the collaboration of all those interested, since the Joint Committee for Higher Surgical Training represents all the surgical Colleges, the specialist associations, and the Association of Professors of Surgery. It is perhaps less than charitable to term this development "untidy". During the past three years, consideration in depth has been given to the place of the primary and final fellowship examination by the English College. There is general agreement that those embarking on a surgical career require to be examined in the basic medical sciences at an early stage. There is also agreement that an assessment in surgery in general is important before specialisation begins. The combination of these examinations is likely to produce an unacceptably complex and difficult test which might even lower standards. Thus there are good reasons for retaining the content and timing of the English primary and fellowship as they are at present-a conclusion that has been reached by recent and exhaustive analysis. There remains the difficult problem of formal assessment towards the end of higher surgical training in each specialty, including general surgery. No realist could advocate a detailed examination for surgeons of considerable seniority, but an interview and discussion of clinical and basic-science literature might well be appropriate before accreditation. Consideration 1.
Spodick, B.,
and others. Lancet, 1978,
i,
1214.
Letters
to
the Editor
would argue with the logic of "controlled surgery" proposed by Professor Spodick and his colleagues.’ As a surgeon, I would be delighted to see such trials, but the major question is how shall they be done? For most procedures, this would require a multicentre approach with all its inherent problems. One only needs to examine the results of some completed trials to see the problems involved, even in
SIR,-No
one
trials in
IMMUNOSTIMULATION FOR CHRONIC ACTIVE HEPATITIS
SIR,-Although the pathogenesis of chronie active hepatitis (C.A.H.) is not fully understood the indications are that this devastating liver disease is mainly due to an impaired immune response, unable to eliminate liver cells infected with hepatitis control autoimmune reactions. If this hypothesis is why, instead of immunosuppression, not try to improve the patient’s immunity and help to eliminate viral infection and naturally suppress the clones of immune cells responsible for autoimmunity? We have tested this idea with B.c.G. vaccine, a potent, mostly cell-mediated, stimulator of the defence system. Twenty children with C.A.H. were selected (thirteen boys and five girls aged 3-15 years). Six children had previously been treated with steroids and azathioprine. The effect of B.c.G. vaccination was monitored by clinical observation, biochemistry, and histology, and immunity was investigated by skin tests with tuberculin and dinitrochlorobenzene. (D.N.C.B.). The children were vaccinated intradermally with B.c.G. vaccine (Poland strain) weekly, and with increasing volume of vaccine. The starting dose was 0.2 ml per injection; the final one was 1 ml for each multifocal injection. Every three subsequent injections were separated by an interval of 1 month, after which the patient was vaccinated again, with a larger dose up to 1 ml B.c.G. vaccine. The patients were given a total of 5.4 ml (0 - 27 mg dry mass of mycobacteria). The reactions to the injections consisted of local ones similar to those after smallpox vaccination, lasting up to 4 months and leaving a flat scar, and an influenza-like reaction (fever, chills, headache, muscle pains) lasting 1-4 days. The reactions were proportional to the dose of vaccine. The effect of B.c.G. vaccination was evaluated 1 year afterwards (see table).
virus
or
correct
INDICATORS OF C.A.H. AND IMMUNE FUNCTION IN 20 CHILDREN BEFORE AND AFTER COURSE OF B.C.G. INJECTIONS
*60-1000 Reitman-Frankel units. tHistology in the remaining 11 patients revealed 1 normal liver, 3 minimal hepatitis, and 7 with improvements. C.E.P.=Counterelectrophoresis. R.l.A.=radioimmunoassay.
The results indicate that B.C.G. vaccine stimulation in children with c.A.H. has therapeutic possibilities. The clinical improvement, return to normal liver function, and elimination of HBsAg (in several cases) are promising. In all children there was long-lasting clinical and biochemical improvement. The worst histology was observed in those who, before vaccine stimulation, had been treated by immunosuppression. Immunosuppression should be applied with circumspection in C.A.H., especially now that there is the alternative of B.C.G. stimulation. of Immunopathology, Institute of Infectious and Parasitic Diseases, Medical Academy in Warsaw, 01-201 Warsaw, Poland
WITOLD
Municipal Hospital for for Children, Warsaw
R. DEBSKI KRYSTYNA DERECKA
Department
Infectious Diseases
J. BRZOSKO
as
areas. For example, the University Group Diabetes Program and the multicentre trial on low-dose heparin have been the subject of bitter controversy. Where does the truth lie in these studies? It is unfortunate that Spodick et al. looked only in the surgical mirror when making their criticisms. A multicentre trial would probably work if it did not involve people-yes, scientists-who in the search for truth often tend to act in a way more human than scientific. One thing that has impressed me in working in new areas with new challenges is how very difficult it is to be completely honest. It is so easy to ignore, skip over, and leave out those parts of the puzzle which appear irrelevant, particularly if you start out with a bias to which your name is attached. How often have Spodick et al. seen a prominent physician, in writing or before an audience, say "I made a terrible mistake based upon a lousy experiment and bad data"? This is a rare happening. I have never seen it. I agree that we must urge continued scepticism for all new therapies and plead with those who toil in this area to employ good science and not worry about the publication filter, which in many cases is no better than the material which is submitted under the guise of science.
non-surgical
Department of Surgery, School of Medicine, University of Washington, Seattle, Washington 98195, U.S.A.
D. E. STRANDNESS
TRAINING FOR SURGERY
SIR,-We were interested in your editorial on surgical train-
ing (July 8, p. 82). We agree that training, examination,
and assessment should be differentiated. However, we must take issue with the suggestion that no thought has been given to these problems in surgery outside the Edinburgh College. The advent and establishment of higher surgical training during the past six years represents a major advance in the final preparation of a surgeon for his consultant job. It has been achieved in a short time and by the collaboration of all those interested, since the Joint Committee for Higher Surgical Training represents all the surgical Colleges, the specialist associations, and the Association of Professors of Surgery. It is perhaps less than charitable to term this development "untidy". During the past three years, consideration in depth has been given to the place of the primary and final fellowship examination by the English College. There is general agreement that those embarking on a surgical career require to be examined in the basic medical sciences at an early stage. There is also agreement that an assessment in surgery in general is important before specialisation begins. The combination of these examinations is likely to produce an unacceptably complex and difficult test which might even lower standards. Thus there are good reasons for retaining the content and timing of the English primary and fellowship as they are at present-a conclusion that has been reached by recent and exhaustive analysis. There remains the difficult problem of formal assessment towards the end of higher surgical training in each specialty, including general surgery. No realist could advocate a detailed examination for surgeons of considerable seniority, but an interview and discussion of clinical and basic-science literature might well be appropriate before accreditation. Consideration 1.
Spodick, B.,
and others. Lancet, 1978,
i,
1214.
