1154 CIMETIDINE AND RENAL-ALLOGRAFT REJECTION
SIR,—Dr Primack (April 15, p. 824) feels that cimetidine may have disadvantages in renal transplantation because it may stimulate elements of the immune system involved in allograft rejection. In our experience with the drug’ we observed no significant difference in graft survival over six weeks between cimetidine-treated and untreated adult renal transplant recipients. The incidence of upper gastrointestinal hxmorrhage was reduced in the treated group. Since we reported these findings, seven transplanted patients have received cimetidine (400-1000 mg daily for 10-21 weeks) without any apparent increase in frequency or severity of rejection
episodes. The dose of cimetidine should be carefully adjusted according to renal function. We have confirmed the findings of Canavan and Briggs2 that 200 mg given twice daily to hxmodialysis patients achieves therapeutic levels without drug accumulation and this is our starting dose for adult renal transplant recipients, gradually increasing to 1000 mg daily as renal function improves. It is possible that 150 mg given twice daily to an 11 kg child with a creatinine clearance of 20 ml/min on the fourth postoperative day may result in high blood levels. We think that there is insufficient evidence to’ attribute transplant rejection to the use of cimetidine, but in view of its immunological actions discussed by Dr Avella and colleagues (March 25, p. 624) and Dr Jones and Professor Greaves (April 22, p. 881) we agree that the use of the drug in organ transplants requires further prospective studies. C. J. RUDGE
R. H. JONES King’s College Hospital Dulwich Hospital,
M. BEWICK M. J. WESTON V. PARSONS
Renal Unit,
London SE22
Intrinsic variation in patients will inevitably lead to a wide of results, as the data of Collins et al. confirm. The patients varied in weight between 35 and 99 kg, yet no attempt was made to express the data in terms of body-weight. Although changes occur after surgery, the standard deviations for total-body nitrogen and total-body potassium are so large that differences between control, aminoacid infusion, and hyperalimentation groups are difficult to interpret. The data certainly do not support the sweeping conclusions drawn. Furthermore if total-body-nitrogen estimations yield data of such limited value should patients be exposed to fast-neutron irradiation for this purpose? scatter
Department of Surgery, University of Newcastle upon Tyne, Royal Victoria Infirmary, Newcastle upon Tyne NE 14LP The
P. D. WRIGHT A. J. RICH
LUNG CANCER AND AIR POLLUTION
SIR,—Dr Lloyd’s analysis (Feb. 11, p. 318) of mortality data in a Scottish town is one of many interesting studies in the area of risk associated with air pollution. As Lloyd states, the effect of air pollution is confounded with cigarette smoking. Lloyd’s remark that the "deaths could not be attributed solely to tobacco" says something of the smoking habits of the 53 deceased persons as a group, but did smoking habits vary by region within the town? Both a high concentration of heavy smokers and proximity to the steel factory could explain the excess mortality from respiratory cancer in area 5. Without information on regional smoking habits, the excess mortality in area 5 cannot be solely attributed to proximity to the steel
factory. Biometry Section, Tobacco and Health Research Institute, University of Kentucky,
INTRAVENOUS HYPERALIMENTATION
SIR,— Mr Collins and his colleagues (April 15, p. 788) in their study of protein-sparing therapies after major surgery conclude that aminoacid infusions were of little use but that "skilled, administration" of intravenous hyperalimentation was very beneficial. Matching of groups of patients is difficult in these circumstances ; all the same, matching in this study does not seem adequate. Two patients with cancer are matched with inflammatory bowel disease despite evidence that malignant disease is associated with metabolic changes which might be expected to influence of observations independently of surgery. No attempt was made to match the patients in respect of factors known to influence some of the complications on which Collins et al. base their conclusions. For example, postoperative wound infection4 is influenced by age, steroids, and preoperative stay as well as by the duration of operation and length of incision. Duration of postoperative hospital stay is not a good index of morbidity.s For example, two patients given intravenous hyperalimentation were discharged on day 25 yet their wounds took 1 and 3 months to heal. Terms such as "wound healing" and "pneumonia" need precise definition. The many studies done on postoperative intravenous feeding suggest that differences in complicationrates between fed and unfed groups will be small, so careful attention to scientific method will be necessary to disclose their
prolonged
true frequency.
Jones, R. H., Rudge, C. J., Bewiek, M., Parsons, V., Weston, M. J. Bri. med. J. 1978, i, 398. 2. Canavan, J. S. F., Briggs, J. D. in Cimetidine (edited by W. R. Burland and 1.
M. A. Simkins); p. 75. Amsterdam 1977. 3. Craig, A. B., Waterhouse, C. Cancer, 1957, 10, 4. Ann. Surg., 1964, 160, supp. no. 2. 5. Rich, A. J., Wright, P. D. Lancet, 1978, 1, 281.
1106.
Lexington, Kentucky 40506, U.S.A.
DENNIS G. HAACK
INTRAMUCOSAL GASTRIC CANCER
SIR,-Professor Clark (April 29, p. 939) questions the type treatment given to two of the patients with mucocancer reported by Dr Taylor and colleagues (April 1, p. 686). Whilst I accept that recurrence in the gastric remnant is found in more than 50% of patients who die after unsuccessful gastrectomies for cancer,’ I do not feel that this justifies, as Clark suggests, total gastrectomy for mucosal gasof operative sal gastric
The excellent results of the treatment of both and advanced gastric cancer reported from Japan rest on excision of the tumour, with an adequate margin of clearance, together with the associated lymph fields in continuity.2 I can find no reference for Clark’s statement that the Japanese results are attributable to the practice of total gastrectomy on this type of cancer. Total gastrectomy has mistakenly become synonymous with radical gastrectomy for cancer. In most body and antral cancers radical gastrectomy is possible without removal of the whole stomach and with considerably less morbidity and mortric
cancer.
"early"
tality. and Mr Menzies-Gow (April 29, p. 939) in their Clark’s letter drew different conclusions than we did from our work.3 We found no obvious differences in the clinical, morphological, or histological characteristics of Japanese and British "early" gastric cancer, and I would suggest that Dr
reply
Taylor
to
McNeer, G., Sunderland, D. A., McInnes, G., Vandenberg, H. J., Lawrence, W. Cancer, 1951, 4, 957. 2. Kajitani,T. Gann Monogr. 1968, 3, 245. 3. Evans, D. M. D., Craven, J. L., Murphy, F., Cleary, B. K. Gut, 1978, 19, 1.
1.
SIR,—Dr Primack (April 15, p. 824) feels that cimetidine may have disadvantages in renal transplantation because it may stimulate elements of the immune system involved in allograft rejection. In our experience with the drug’ we observed no significant difference in graft survival over six weeks between cimetidine-treated and untreated adult renal transplant recipients. The incidence of upper gastrointestinal hxmorrhage was reduced in the treated group. Since we reported these findings, seven transplanted patients have received cimetidine (400-1000 mg daily for 10-21 weeks) without any apparent increase in frequency or severity of rejection
episodes. The dose of cimetidine should be carefully adjusted according to renal function. We have confirmed the findings of Canavan and Briggs2 that 200 mg given twice daily to hxmodialysis patients achieves therapeutic levels without drug accumulation and this is our starting dose for adult renal transplant recipients, gradually increasing to 1000 mg daily as renal function improves. It is possible that 150 mg given twice daily to an 11 kg child with a creatinine clearance of 20 ml/min on the fourth postoperative day may result in high blood levels. We think that there is insufficient evidence to’ attribute transplant rejection to the use of cimetidine, but in view of its immunological actions discussed by Dr Avella and colleagues (March 25, p. 624) and Dr Jones and Professor Greaves (April 22, p. 881) we agree that the use of the drug in organ transplants requires further prospective studies. C. J. RUDGE
R. H. JONES King’s College Hospital Dulwich Hospital,
M. BEWICK M. J. WESTON V. PARSONS
Renal Unit,
London SE22
Intrinsic variation in patients will inevitably lead to a wide of results, as the data of Collins et al. confirm. The patients varied in weight between 35 and 99 kg, yet no attempt was made to express the data in terms of body-weight. Although changes occur after surgery, the standard deviations for total-body nitrogen and total-body potassium are so large that differences between control, aminoacid infusion, and hyperalimentation groups are difficult to interpret. The data certainly do not support the sweeping conclusions drawn. Furthermore if total-body-nitrogen estimations yield data of such limited value should patients be exposed to fast-neutron irradiation for this purpose? scatter
Department of Surgery, University of Newcastle upon Tyne, Royal Victoria Infirmary, Newcastle upon Tyne NE 14LP The
P. D. WRIGHT A. J. RICH
LUNG CANCER AND AIR POLLUTION
SIR,—Dr Lloyd’s analysis (Feb. 11, p. 318) of mortality data in a Scottish town is one of many interesting studies in the area of risk associated with air pollution. As Lloyd states, the effect of air pollution is confounded with cigarette smoking. Lloyd’s remark that the "deaths could not be attributed solely to tobacco" says something of the smoking habits of the 53 deceased persons as a group, but did smoking habits vary by region within the town? Both a high concentration of heavy smokers and proximity to the steel factory could explain the excess mortality from respiratory cancer in area 5. Without information on regional smoking habits, the excess mortality in area 5 cannot be solely attributed to proximity to the steel
factory. Biometry Section, Tobacco and Health Research Institute, University of Kentucky,
INTRAVENOUS HYPERALIMENTATION
SIR,— Mr Collins and his colleagues (April 15, p. 788) in their study of protein-sparing therapies after major surgery conclude that aminoacid infusions were of little use but that "skilled, administration" of intravenous hyperalimentation was very beneficial. Matching of groups of patients is difficult in these circumstances ; all the same, matching in this study does not seem adequate. Two patients with cancer are matched with inflammatory bowel disease despite evidence that malignant disease is associated with metabolic changes which might be expected to influence of observations independently of surgery. No attempt was made to match the patients in respect of factors known to influence some of the complications on which Collins et al. base their conclusions. For example, postoperative wound infection4 is influenced by age, steroids, and preoperative stay as well as by the duration of operation and length of incision. Duration of postoperative hospital stay is not a good index of morbidity.s For example, two patients given intravenous hyperalimentation were discharged on day 25 yet their wounds took 1 and 3 months to heal. Terms such as "wound healing" and "pneumonia" need precise definition. The many studies done on postoperative intravenous feeding suggest that differences in complicationrates between fed and unfed groups will be small, so careful attention to scientific method will be necessary to disclose their
prolonged
true frequency.
Jones, R. H., Rudge, C. J., Bewiek, M., Parsons, V., Weston, M. J. Bri. med. J. 1978, i, 398. 2. Canavan, J. S. F., Briggs, J. D. in Cimetidine (edited by W. R. Burland and 1.
M. A. Simkins); p. 75. Amsterdam 1977. 3. Craig, A. B., Waterhouse, C. Cancer, 1957, 10, 4. Ann. Surg., 1964, 160, supp. no. 2. 5. Rich, A. J., Wright, P. D. Lancet, 1978, 1, 281.
1106.
Lexington, Kentucky 40506, U.S.A.
DENNIS G. HAACK
INTRAMUCOSAL GASTRIC CANCER
SIR,-Professor Clark (April 29, p. 939) questions the type treatment given to two of the patients with mucocancer reported by Dr Taylor and colleagues (April 1, p. 686). Whilst I accept that recurrence in the gastric remnant is found in more than 50% of patients who die after unsuccessful gastrectomies for cancer,’ I do not feel that this justifies, as Clark suggests, total gastrectomy for mucosal gasof operative sal gastric
The excellent results of the treatment of both and advanced gastric cancer reported from Japan rest on excision of the tumour, with an adequate margin of clearance, together with the associated lymph fields in continuity.2 I can find no reference for Clark’s statement that the Japanese results are attributable to the practice of total gastrectomy on this type of cancer. Total gastrectomy has mistakenly become synonymous with radical gastrectomy for cancer. In most body and antral cancers radical gastrectomy is possible without removal of the whole stomach and with considerably less morbidity and mortric
cancer.
"early"
tality. and Mr Menzies-Gow (April 29, p. 939) in their Clark’s letter drew different conclusions than we did from our work.3 We found no obvious differences in the clinical, morphological, or histological characteristics of Japanese and British "early" gastric cancer, and I would suggest that Dr
reply
Taylor
to
McNeer, G., Sunderland, D. A., McInnes, G., Vandenberg, H. J., Lawrence, W. Cancer, 1951, 4, 957. 2. Kajitani,T. Gann Monogr. 1968, 3, 245. 3. Evans, D. M. D., Craven, J. L., Murphy, F., Cleary, B. K. Gut, 1978, 19, 1.
1.
