24 lence of both reflux and kidney scarring seems to be 10-20 times higher in school-aged siblings than in unselected school children. From a practical viewpoint a case can be made for radiological investigation of any firstdegree relative of a child who has severe reflux and gross kidney damage, because of the possibility of finding similar severe damage in the relative. But the value of detecting reflux which is not associated with renal damage is less certain. It depends upon how dangerous you consider reflux. Fewer and fewer people now subscribe to the view that reflux in the absence of infection damages the kidneys. Many people believe that reflux, even when associated with infection, does not cause important functional kidney damage over the age of 5 years,12 unless there is urinary-tract obstruction also. Below the age of 5 there are insufficient data for any conclusions to be drawn. The need for long-term studies of infants and preschool children with reflux is well recognised. How might such a group be assembled? Firstly, both neonates"’" and preschool children16,17 can be reliably screened for bacteriuria, and those with it will yield a smaller group with reflux. Secondly, the young siblings of any child who is found to have reflux will yield a substantial proportion who themselves have reflux. Until there is more knowledge about the importance, the natural history, and the unnatural treated history of such young children with reflux, there can be no strong case
for widespread radiological screening.
MATERNAL AGE AND DOWN’S SYNDROME THE risk of bearing an infant with Down’s syndrome rises sharply with advancing maternal age. Liveborn surveys show an incidence of about 6 per 1000 for mothers over the age of 35, the relative risks being about 0-4% for the age-bracket 35-39, 1-2% for age-bracket 40-44, and 4% for those 45 years of age or older.1-3 These figures have been important both in cost-benefit calculations for prenatal-diagnosis screening programmes and in counselling of the older mother about her risk of bearing an abnormal child. With the increasing availability of early prenatal diagnosis, it now seems that the risk of Down’s syndrome culled from analyses of amniocentesis material is substantially greater than that derived from liveborn surveys. In the age-group 35-39 amniocentesis-based risks range from 0.55% to 1-4%, while in the age-group 40-44 they have been variously cited as between 2.7% and 3-8%/-’’ Part of the explanation for this variation lies in the small number of amniocentesis samples which have been karyotyped in individual laboratories. However, in a large collaborative survey of prenatal-diag12. Cardiff-Oxford Bacteriuria Study Group, Lancet, April 29, 1978, p. 889. 13. Littlewood, J. M., Kite, P., Kite, B. A. Archs Dis. Childh. 1969, 44, 617. 14. Abbott, G. D. Br. med. J. 1972, i, 267. 15. Edelmann, C. M., Jr., Ogwo, J. E., Fine, B. P., Martinez, A. B. J. Pediat.
1973, 82, 125. J. M., Gibson, G. L., Littlewood, J. M., Meadow, S. R. Lancet, 1974, ii, 7. 17. Saxena, S. R., Collis, A., Laurance, B. M. Practitioner, 1975, 214, 257. 1. Collman, R. D., Stoller, A. Am. J. publ. Hlth, 1962, 52, 813. 2. Lindsjo, A. Acta pædiat scand. 1974, 63, 571. 3. Hook, E. Lancet, 1976, ii, 33. 4. Hook, E. ibid. 1978, i, 1053. 5. Ferguson-Smith, M. A., Ferguson-Smith, M. E. J. clin. Path. 1976, 29, suppl. 10, p. 165. 16. Davies,
experience presented at the 3rd European Prenatal Diagnosis Conference, the relative risks were found to be 0.93% and 2.5% for age-groups 35-39 and 40-44, respectively.6 These are more than double the risks expected from liveborn figures. Is this discrepancy real or an artifact? There are several possible confounding factors when incidence figures in livebirths are compared with those in prenatal studies. Hookhas suggested that amniocentesis data from laboratories with high detection-rates for fetal chromosome abnormalities may be preferentially reported because they contrast strikingly with rates found at birth. Pooling of maternal ages into 5-year brackets (35-39, 40-44) will lead to different distribunosis
tions in the amniocentesis data, where the older mother will be strongly represented, compared with the liveborn data, where the usual fall-off in birth-rate with advancing age will be seen. Maternal ages must be corrected to allow for the fact that amniocentesis usually takes place about five months before delivery. This means that about half of a group of 39-year-olds undergoing amniocentesis will appear in the liveborn risk tables as 40-year-olds. Since the risk of Down’s syndrome increases at about 30% a year after age 30,7 this factor could be important. However, when allowance is made for these confounders the discrepancy seems to persist, at least in the 40-44-year group68 and probably also in the 35-39-year group.6 Part of the almost two-fold excess of Down’s syndrome in prenatal data among 40-44-yearold mothers can be attributed to fetal loss between 16 weeks’ gestation and term. On the basis of cytogenetic studies on spontaneous abortions it has been suggested that some 20% of Down’s fetuses alive at 16 weeks may be lost before birth.9 One possibility is that older mothers have a higher preferential expulsion-rate of abnormal fetuses than younger mothers, but it would have to be two or three times as high. It seems more likely that older mothers who seek prenatal diagnosis may be a high-risk sample of their age-group because of poor obstetric histories. Polani et a1.9 have presented limited but suggestive evidence that older mothers attending their clinic had increased exposure to X-rays and higher rates of spontaneous miscarriage and subfertility. If this is confirmed it may represent a short-term phenomenon which will disappear as a wider section of older mothers avail themselves of prenatal diagnosis. On the other hand, since amniocentesis data are generally of more recent origin than liveborn data, they may be defining a genuine increase in the age-specific incidence of Down’s syndrome. What are the implications for prenatal counselling? Should the counsellor cite the risk of an infant being born alive with Down’s syndrome or the higher risk in the fetus at the time of amniocentesis? Should he include the additional risks of other chromosome abnormalities, knowing that many other autosomal aneuploidies abort spontaneously or are stillborn while a majority of sexchromosome abnormalities are relatively harmless? 6. Proc III Europ. prenat. Diag. Conf., Munich, April, 1978 in the press). 7. Hook, E., Chambers, G. C. Birth Defects orig. Art Ser. 1977, 13 (3A), 123. 8. Spielman, R. S., Mennuti, M. T., Zackai, E. H., Mellman, W. J. Lancet. 9.
1978, i, 1306. Polani, P. E., Alberman, E., Barry, A. C., Blunt, S., Singer, J. D. ibid. 1976, ii, 516.
25
There are those who argue that the liveborn rate of is the only suitable counselling Down’s and those contend that women must be prewho figure10 sented with the real incidence of aneuploidy at the time of their amniocentesis." For mothers over 40 the distinction is perhaps not critical, since the risk of Down’s syndrome is greater than 1% whichever way it is calculated. But for those under 40 the different risk figures may lead to quite different responses to the suggestion of amniocentesis and prenatal diagnosis. The complexity and incompleteness of the data make counselling of the older mother a delicate matter. A key factor which has to be taken into consideration is the rate of fetal morbidity and mortality associated with the act of amniocentesis itself. Two surveys12,13 suggest that fetal mortality is less than 1%, but if amniocentesis becomes more widespread this may prove to be a conservative estimate. Though it is perhaps unwise to equate the rates of fetal loss from amniocentesis with the rates of expected fetal abnormality, these figures are undoubtedly highly influential when prenatal diagnosis is under consideration. Perhaps some genetic counsellors have been taking too much responsibility upon themselves and the correct course of action is to advise the older mother of the unresolved discrepancies between liveborn and amniocentesis rates of Down’s syndrome, to acquaint them with the possible complications of amniocentesis itself, and to allow them to use their own judgment of which risks pose the greater threat.
syndrome
,
OPERATIONS FOR DIVERTICULAR DISEASE SINCE the dietary-fibre boom, the number of operations done for uncomplicated diverticular disease has fallen impressively. A panel at the lst World Congress of Colo-Proctology, Madrid, agreed that surgery should now be reserved for complications. In the view of Loygue, of Paris, resection is mainly indicated for severe abdominal pain, subacute obstruction, abscess or a persistent mass, the possible existence of malignant disease, and persistent uncontrolled haemorrhage. Smith of Edinburgh contrasted resection and myotomy. He stressed the importance of the smooth muscle, seeing the diverticulum as a secondary extrusion of the mucosa. Fibre and fibre-like bulk agents reduced the intraluminal pressure mainly by adding to the bulk of the faeces, part of this action being due to increased adsorption of water. Myotomy likewise lowered the pressure, and the effect was maintained for two to three years; thereafter, the pressure rose gradually and symptoms tended to recur. Resection did not lower pressure in the distal sigmoid colon and upper rectum, but complications were less frequent after this operation. After either myotomy or resection, the patient ought to take bran postoperatively to keep the pressure down. Myotomy carries a risk of dehiscence or operative puncture with resultant pelvic abscess and even death, so the panel judged that the operation should be reserved for elderly patients who are 10. 11.
Wyatt, P. R. ibid. 1978, i, 1305. Kardon, N., Krauss, M., Silverberg, G., Davis, J. ibid. p. 1305. 12. N.I.C.H.D. National Registry for Amniocentesis Study Group. J. Am. med. Ass 1976, 236, 1471. 13. Simpson, N. E., Dallaire, L., Miller, J. R., Simonovich, L., Hamerton, J. L., Miller, J., McKeen, C. Can. med. Ass. J. 1976, 115, 739.
frail for more radical surgery, to people with especially thick muscle, and to people with localised disease in the pelvic colon. In most cases the correct operation is resection, often with a "covering" colostomy. Wide resection was not advocated. It was more important to resect bowel in the pelvis than towards the splenic flexure. The operation of transverse taeniamyotomy was discussed; this procedure, developed by Hodgson and extended by Pescatori of Rome might be safer than longitudinal myotomy. Rohner of Geneva discussed operative surprises. The commonest was more extensive obstruction or more diffuse inflammation than expected. Sometimes it was hard to say whether the affected diverticular segment contained a carcinoma, though bleeding due to a tumour was usually slight compared with that due to diverticular disease. Barium enema left a 20% group of doubtful cases. Colonoscopy was difficult and could be dangerous. too
The panel then turned to more complicated forms of diverticular disease. Puig La Calle discussed the management of abscess, fistula, and obstruction. Abscess "in the making" should be treated medically; riper abscesses should be drained, with or without a colostomy. Frank fistula of the communicating type, indicated by a faecal discharge, was preferably managed by an exteriorisation operation. Extension to the bladder could be treated in one stage, but more complicated fistulas, through an abscess cavity, for example, required the three stages of preliminary defunctioning colostomy, dismantling of the fistula, and colostomy closure. The differential diagnosis from a Crohn’s fistula had always to be kept in mind, and some patients had both conditions. Obstructions tended to settle spontaneously, the usual cause being ileus due to adjacent peritonitis. If it did not settle, some other diagnosis, such as carcinoma, had to be thought of. Perforation was perhaps the severest complication and here the general treatment, particularly resuscitation, was important. Puig La Calle maintained that suture and drainage with protective colostomy, although reckoned the least severe procedure for the patient, had a higher mortality than primary resection or Hartmann’s operation.
-
Slack, of the Middlesex Hospital, London, discussed the management of haemorrhage. In the minor form there was blood in the stool, often no pain, and the source was an inflammatory ulcer in the most involved segment, mainly the sigmoid colon. In major bleedingusually copious discharge of bright-red blood-sigmoidoscopy and colonoscopy were difficult and often fruitless, since the blood obscured everything. This sort of bleeding probably came from major vessels running over the diverticulum. With replacement of blood the bleeding usually stopped; but, if it did not, subtotal colectomy was a better course than attempting a transverse colostomy to see where the blood was coming from. Angiography might be useful, possibly with embolisation of the affected blood-vessel. Whether fibre deficiency is the cause of diverticular disease remains to be seen. If it is, we may expect to see a decline in its incidence and a further drop in the number of operations required. Meanwhile, the panel were at one in declaring that conservative management should continue as long as possible.
for widespread radiological screening.
MATERNAL AGE AND DOWN’S SYNDROME THE risk of bearing an infant with Down’s syndrome rises sharply with advancing maternal age. Liveborn surveys show an incidence of about 6 per 1000 for mothers over the age of 35, the relative risks being about 0-4% for the age-bracket 35-39, 1-2% for age-bracket 40-44, and 4% for those 45 years of age or older.1-3 These figures have been important both in cost-benefit calculations for prenatal-diagnosis screening programmes and in counselling of the older mother about her risk of bearing an abnormal child. With the increasing availability of early prenatal diagnosis, it now seems that the risk of Down’s syndrome culled from analyses of amniocentesis material is substantially greater than that derived from liveborn surveys. In the age-group 35-39 amniocentesis-based risks range from 0.55% to 1-4%, while in the age-group 40-44 they have been variously cited as between 2.7% and 3-8%/-’’ Part of the explanation for this variation lies in the small number of amniocentesis samples which have been karyotyped in individual laboratories. However, in a large collaborative survey of prenatal-diag12. Cardiff-Oxford Bacteriuria Study Group, Lancet, April 29, 1978, p. 889. 13. Littlewood, J. M., Kite, P., Kite, B. A. Archs Dis. Childh. 1969, 44, 617. 14. Abbott, G. D. Br. med. J. 1972, i, 267. 15. Edelmann, C. M., Jr., Ogwo, J. E., Fine, B. P., Martinez, A. B. J. Pediat.
1973, 82, 125. J. M., Gibson, G. L., Littlewood, J. M., Meadow, S. R. Lancet, 1974, ii, 7. 17. Saxena, S. R., Collis, A., Laurance, B. M. Practitioner, 1975, 214, 257. 1. Collman, R. D., Stoller, A. Am. J. publ. Hlth, 1962, 52, 813. 2. Lindsjo, A. Acta pædiat scand. 1974, 63, 571. 3. Hook, E. Lancet, 1976, ii, 33. 4. Hook, E. ibid. 1978, i, 1053. 5. Ferguson-Smith, M. A., Ferguson-Smith, M. E. J. clin. Path. 1976, 29, suppl. 10, p. 165. 16. Davies,
experience presented at the 3rd European Prenatal Diagnosis Conference, the relative risks were found to be 0.93% and 2.5% for age-groups 35-39 and 40-44, respectively.6 These are more than double the risks expected from liveborn figures. Is this discrepancy real or an artifact? There are several possible confounding factors when incidence figures in livebirths are compared with those in prenatal studies. Hookhas suggested that amniocentesis data from laboratories with high detection-rates for fetal chromosome abnormalities may be preferentially reported because they contrast strikingly with rates found at birth. Pooling of maternal ages into 5-year brackets (35-39, 40-44) will lead to different distribunosis
tions in the amniocentesis data, where the older mother will be strongly represented, compared with the liveborn data, where the usual fall-off in birth-rate with advancing age will be seen. Maternal ages must be corrected to allow for the fact that amniocentesis usually takes place about five months before delivery. This means that about half of a group of 39-year-olds undergoing amniocentesis will appear in the liveborn risk tables as 40-year-olds. Since the risk of Down’s syndrome increases at about 30% a year after age 30,7 this factor could be important. However, when allowance is made for these confounders the discrepancy seems to persist, at least in the 40-44-year group68 and probably also in the 35-39-year group.6 Part of the almost two-fold excess of Down’s syndrome in prenatal data among 40-44-yearold mothers can be attributed to fetal loss between 16 weeks’ gestation and term. On the basis of cytogenetic studies on spontaneous abortions it has been suggested that some 20% of Down’s fetuses alive at 16 weeks may be lost before birth.9 One possibility is that older mothers have a higher preferential expulsion-rate of abnormal fetuses than younger mothers, but it would have to be two or three times as high. It seems more likely that older mothers who seek prenatal diagnosis may be a high-risk sample of their age-group because of poor obstetric histories. Polani et a1.9 have presented limited but suggestive evidence that older mothers attending their clinic had increased exposure to X-rays and higher rates of spontaneous miscarriage and subfertility. If this is confirmed it may represent a short-term phenomenon which will disappear as a wider section of older mothers avail themselves of prenatal diagnosis. On the other hand, since amniocentesis data are generally of more recent origin than liveborn data, they may be defining a genuine increase in the age-specific incidence of Down’s syndrome. What are the implications for prenatal counselling? Should the counsellor cite the risk of an infant being born alive with Down’s syndrome or the higher risk in the fetus at the time of amniocentesis? Should he include the additional risks of other chromosome abnormalities, knowing that many other autosomal aneuploidies abort spontaneously or are stillborn while a majority of sexchromosome abnormalities are relatively harmless? 6. Proc III Europ. prenat. Diag. Conf., Munich, April, 1978 in the press). 7. Hook, E., Chambers, G. C. Birth Defects orig. Art Ser. 1977, 13 (3A), 123. 8. Spielman, R. S., Mennuti, M. T., Zackai, E. H., Mellman, W. J. Lancet. 9.
1978, i, 1306. Polani, P. E., Alberman, E., Barry, A. C., Blunt, S., Singer, J. D. ibid. 1976, ii, 516.
25
There are those who argue that the liveborn rate of is the only suitable counselling Down’s and those contend that women must be prewho figure10 sented with the real incidence of aneuploidy at the time of their amniocentesis." For mothers over 40 the distinction is perhaps not critical, since the risk of Down’s syndrome is greater than 1% whichever way it is calculated. But for those under 40 the different risk figures may lead to quite different responses to the suggestion of amniocentesis and prenatal diagnosis. The complexity and incompleteness of the data make counselling of the older mother a delicate matter. A key factor which has to be taken into consideration is the rate of fetal morbidity and mortality associated with the act of amniocentesis itself. Two surveys12,13 suggest that fetal mortality is less than 1%, but if amniocentesis becomes more widespread this may prove to be a conservative estimate. Though it is perhaps unwise to equate the rates of fetal loss from amniocentesis with the rates of expected fetal abnormality, these figures are undoubtedly highly influential when prenatal diagnosis is under consideration. Perhaps some genetic counsellors have been taking too much responsibility upon themselves and the correct course of action is to advise the older mother of the unresolved discrepancies between liveborn and amniocentesis rates of Down’s syndrome, to acquaint them with the possible complications of amniocentesis itself, and to allow them to use their own judgment of which risks pose the greater threat.
syndrome
,
OPERATIONS FOR DIVERTICULAR DISEASE SINCE the dietary-fibre boom, the number of operations done for uncomplicated diverticular disease has fallen impressively. A panel at the lst World Congress of Colo-Proctology, Madrid, agreed that surgery should now be reserved for complications. In the view of Loygue, of Paris, resection is mainly indicated for severe abdominal pain, subacute obstruction, abscess or a persistent mass, the possible existence of malignant disease, and persistent uncontrolled haemorrhage. Smith of Edinburgh contrasted resection and myotomy. He stressed the importance of the smooth muscle, seeing the diverticulum as a secondary extrusion of the mucosa. Fibre and fibre-like bulk agents reduced the intraluminal pressure mainly by adding to the bulk of the faeces, part of this action being due to increased adsorption of water. Myotomy likewise lowered the pressure, and the effect was maintained for two to three years; thereafter, the pressure rose gradually and symptoms tended to recur. Resection did not lower pressure in the distal sigmoid colon and upper rectum, but complications were less frequent after this operation. After either myotomy or resection, the patient ought to take bran postoperatively to keep the pressure down. Myotomy carries a risk of dehiscence or operative puncture with resultant pelvic abscess and even death, so the panel judged that the operation should be reserved for elderly patients who are 10. 11.
Wyatt, P. R. ibid. 1978, i, 1305. Kardon, N., Krauss, M., Silverberg, G., Davis, J. ibid. p. 1305. 12. N.I.C.H.D. National Registry for Amniocentesis Study Group. J. Am. med. Ass 1976, 236, 1471. 13. Simpson, N. E., Dallaire, L., Miller, J. R., Simonovich, L., Hamerton, J. L., Miller, J., McKeen, C. Can. med. Ass. J. 1976, 115, 739.
frail for more radical surgery, to people with especially thick muscle, and to people with localised disease in the pelvic colon. In most cases the correct operation is resection, often with a "covering" colostomy. Wide resection was not advocated. It was more important to resect bowel in the pelvis than towards the splenic flexure. The operation of transverse taeniamyotomy was discussed; this procedure, developed by Hodgson and extended by Pescatori of Rome might be safer than longitudinal myotomy. Rohner of Geneva discussed operative surprises. The commonest was more extensive obstruction or more diffuse inflammation than expected. Sometimes it was hard to say whether the affected diverticular segment contained a carcinoma, though bleeding due to a tumour was usually slight compared with that due to diverticular disease. Barium enema left a 20% group of doubtful cases. Colonoscopy was difficult and could be dangerous. too
The panel then turned to more complicated forms of diverticular disease. Puig La Calle discussed the management of abscess, fistula, and obstruction. Abscess "in the making" should be treated medically; riper abscesses should be drained, with or without a colostomy. Frank fistula of the communicating type, indicated by a faecal discharge, was preferably managed by an exteriorisation operation. Extension to the bladder could be treated in one stage, but more complicated fistulas, through an abscess cavity, for example, required the three stages of preliminary defunctioning colostomy, dismantling of the fistula, and colostomy closure. The differential diagnosis from a Crohn’s fistula had always to be kept in mind, and some patients had both conditions. Obstructions tended to settle spontaneously, the usual cause being ileus due to adjacent peritonitis. If it did not settle, some other diagnosis, such as carcinoma, had to be thought of. Perforation was perhaps the severest complication and here the general treatment, particularly resuscitation, was important. Puig La Calle maintained that suture and drainage with protective colostomy, although reckoned the least severe procedure for the patient, had a higher mortality than primary resection or Hartmann’s operation.
-
Slack, of the Middlesex Hospital, London, discussed the management of haemorrhage. In the minor form there was blood in the stool, often no pain, and the source was an inflammatory ulcer in the most involved segment, mainly the sigmoid colon. In major bleedingusually copious discharge of bright-red blood-sigmoidoscopy and colonoscopy were difficult and often fruitless, since the blood obscured everything. This sort of bleeding probably came from major vessels running over the diverticulum. With replacement of blood the bleeding usually stopped; but, if it did not, subtotal colectomy was a better course than attempting a transverse colostomy to see where the blood was coming from. Angiography might be useful, possibly with embolisation of the affected blood-vessel. Whether fibre deficiency is the cause of diverticular disease remains to be seen. If it is, we may expect to see a decline in its incidence and a further drop in the number of operations required. Meanwhile, the panel were at one in declaring that conservative management should continue as long as possible.
