459
venous
Necrotising Enterocolitis enterocolitis, a serious condition of newborn infants, presents with vomiting, abdominal distension, and passage of blood in the stools; NECROTISING
radiological signs of gas in the bowel wall-pneumatosis intestinalis. In advanced cases the infant is shocked and may have septicaemia and peritonitis; an abdominal X-ray may then show free gas in the peritoneum or portal tract. At laparand there
are
otomy or necropsy there is ischaemic necrosis of the bowel wall, often widespread, with sloughing of the intestinal mucosa.1The first series of cases of necrotising enterocolitis (N.E.C.) were reported from the Babies Hospital, New York, in 1964 and
1965, although individual
cases
indistinguishable
in retrospect from N.E.c. had been recorded.3 4 Over the past ten years the condition has become progressively more common (or has been recognised more widely) in special-care baby units throughout the world.12 5-7 In some units a fivefold increase in incidence has been reported.6 8 Apparently there are striking differences in the incidence of the disease from country to country, from city to city, and even between neonatal units within the same city. The Royal Free Hospital, London, is at present coping with a major outbreak. N.E.C. predominantly affects infants of low birthweight who have been under intensive care; 1-4 in one series9 the frequency below 1200 g was as high as 27%. Infants of very low birthweight under intensive care have in common such factors as birth
asphyxia, hyaline-membrane disease, feeding by nasogastric or nasoduodenal tube, and umbilical arterial catheterisation. N.E.C. is not, however, confined to low-birth weight infants. It has been reported also among heavier infants who have undergone exchange blood-transfusions via umbilical
catheters.10-12 Among 26 cases of N.E.C. fol-
lowing exchange transfusion the mean birthweight was 2700 g.12 Low-birthweight infants tend to acquire N.E.c. in the first few days after birth (in two large series half of the cases had presented within five days of birth7) and the mortality-rate has ranged from around 30%13-15 to zin what seem to be comparable series; the disorder most commonly affects the terminal ileum,16 but it may extend to one or more areas of the large or small bowel or be even more widespread-producing in effect a gastroenterocolitis. In infants who acquire N.E.C. after exchange transfusion the onset is later, the mortality around 20%, and the colon more often affected than other sites in the gastrointestinal tract. 12 N.E.C. (or a condition which seems identical pathologically) has also been reported among infants with primary anatomical lesions of the bowel such as Hirschsprung’s disease, 2and among term infants with congenital heart-disease and primary infective gastroenteritis.111 Treatment of N.E.C. is based on experience rather than experiment. Umbilical catheters are removed, gastrointestinal feeds withheld, the stomach aspirated, fluids given by peripheral infusion, and broad-spectrum antibiotics administered. In infants who settle down on such medical treatment, early reintroduction of feeds has seemingly led to recurrence of the signs ofN.E.C., including pneumatosis intestinalis.7 19 Some workers recommend that the bowel be rested for up to ten days after the initial signs of the disorder have remitted.7 19 In the event of peritonitis, perforation, or a rapid decline in the infant’s condition prompt laparotomy is indicated with resection of the ischaemic segment and construction of an ileostomy or colostomy.1 2 14 15 BELL and others 14 claim that survival-rates improved in low-birthweight infants when kanamycin, at twice the normal parenteral dose, was given through a nasogastric tube. EGAN et a1.,20 in a controlled prospective trial of prophylactic alimentary kanamycin 15 mg/kg/day, have reported prevention of N.E.C. among low-birthweight infants believed to be at risk. However, the numbers in this study were too small for a firm conclusion to be drawn: there were no cases of N.E.C. among the 35 treated infants compared with 5 cases among 40 control infants.
1
Santulli, T. V., Schullinger, J. N., Heird, W. C., Gongaware, R. D., Wigger, J, Barlow, B., Blanc, W. A., Berdon, W. E. Pediatrics, 1975, 55, 376. 2. Dudgeon, D. L., Coran, A. G., Lauppe, F. A., Hodgman, J. E., Rosenkrantz, J. G. J. pediat. Surg. 1973, 8, 607. 3 Berdon, W. E., Grossman, H., Baker, D. H., Mizrahi, A., Barlow, O., Blanc, W. A Radiology, 1964, 83, 879. 4. Mizrahi, A., Barlow, O., Berdon, W., Blanc, W. A., Silverman, W. A. J. Pediat. 1965, 66, 697. 5 Hopkins, G. B., Gould, V. E., Stevenson, J. K., Oliver, T. K. Am. J. Dis. Child 1970, 120, 229. 6 Virnig, N. L., Reynolds, J. W. Am. J. Dis. Child. 1974, 128, 186. 7 Frantz, I. D., Litteureux, P., Engel, R. R., Hunt, C. E.J. Pediat. 1975, 86, 259.
Heese, H. de V. in Intensive Care in the Newborn (edited by L. Stern, B. Friis-Hansen, and P. Kildeberg); p. 73. New York, 1976. 9. Book, L S., Herbst, J. J., Atherton, S. O., Jung, A. L. J. Pediat. 1975, 87, 8.
602.
10. Corkery, J. J., Dubowitz, V., Lister, J., Moosa, A. Br. med. J. 1968, iv, 345. 11. Orme, R. L’E., Eades, S. M. ibid. p. 349. 12. Hardy, J. D., Savage, T. R. Am. J. Dis. Child. 1972, 124, 136. 13. Stevenson, J. K., Graham, C. B., Oliver, T. K., Goldenberg, V. E. Am. J. Surg. 1969, 118, 260. 14. Bell, M. J., Kosloske, A. M., Benton, C., Martin, L. W. J. pediat. Surg.
1973, 8, 601. 15. De Luca, F. G., 16. Touloukian, R.
Wesselhoeft, C. W. Am. J. Surg. 1974, 127, 410. J., Berdon, W. E., Amoury, R. A., Santulli, T. V. J. pediat. Surg. 1967, 2, 389. 17. Bill, A. H., Jr., Chapman, N. D. Am. J. Surg. 1962, 103, 70. 18. Polin, R. A., Pollock, P. F., Barlow, B., Wigger, H. J., Slovis, T. L., Santulli, T. V., Heird, W. C. J. Pediat. 1976, 89, 460. 19. Vollman, J. H., Smith, W. L., Tsang, R. C. J. Pediat. 1976, 88, 486. 20. Egan, E. A., Mantilla, G., Nelson, R. M., Eitzman, D. V. ibid. 1976, 89, 467.
460
Although the cause of N.E.C. is not established, the primary event does seem to be ischaemia of the bowel wall, followed by bacterial invasion, proliferation, and gas formation within the bowel wall. One suggestion,21 which is supported by experiments on asphyxiated newborn piglets,22 is that asphyxia leads to redistribution of cardiac output with reflex constriction of the intestinal vasculature and thence mucosal ischaemia. While this may be the case among low-birthweight infants, in larger infants affected after exchange transfusion the mechanism is probably different. Perhaps pressure changes in the umbilical venous catheter are transmitted through the portal venous system directly affecting mesenteric blood-flow.lU-12 Then there is the suggestion of ROGERS and DUNN23 that the increased incidence of N.E.C. was related to the introduction into neonatal intensive care of polyvinylchloride catheters and feeding-tubes and that the leaching out of plasticisers from P.v.c. produced a toxic disorder of vascular tone in the bowel wall. Lately HiLLMAN and colleagues24 reported substantial concentrations of plasticiser in segments of bowel resected at operation from infants with N.E.C. Other workers believe that gastrointestinal feeding is to blame, relating N.E.C. to high volumes of milk formula25 and to hyperosmolar elemental feeds9-although how such practices might lead to intestinal ischxmia remains to be explained. BARLOW and co-workers26 report that fresh breast milk protects newborn rats against N.E.c., suggesting that humoral or cellular components27 of the fresh milk may confer a passive enteric immunity to direct bacterial invasion. These are exciting observations. In other series the clustering of cases associated with outbreaks of gastroenteritis,18 sometimes due to non-enteropathogenic strains of Escherichia coli,z Salmonella,29 and Clostridia,3u has suggested a primary infective disorder. The various theories do agree that bacterial invasion is an essential step in the development of N.E.C. This does not explain why such a serious disorder should be increasing in incidence in special-care baby units. Maybe it is part of the price we pay for increasing survival of low-birthweight infants. However, those working in intensive-care units must remain vigilant in case N.E.c. represents a new iatrogenic disorder caused by some change in clinical practice.
Surgical Treatment in Chronic Relapsing Pancreatitis CHRONIC relapsing pancreatitis is uncommon in the United Kingdom. Half the cases are secondary to alcoholism;in the remainder the cause is usually obscure-only rarely is the chronic condition a sequel to acute pancreatitis. For most patients the main requirement is supervision and control of their endocrine and exocrine insufficiency, but there are a few who benefit from surgical treatment. Some need operation to relieve obstructive jaundice, or to control haematemesis resulting from splenic-vein thrombosis, or to deal with one of the complications of chronic pancreatitis such as pseudocyst formation or duodenal stenosis, but much the commonest indication for surgery is the severe and crippling pain which may otherwise lead the patient into drug dependence and addiction.
Operations on a healthy biliary tract, notably sphincteroplasty, convey little benefit and, like the nerve-cutting operations, splanchnicectomy and caeliac ganglionectomy, have few advocates nowadays. The nerve-cutting procedures relieve pancreatic pain in about a third of cases but the effect seldom lasts more than a couple of years, while the underlying disease process in the gland is in no way influenced. The operations now in common use are either some form of pancreatic-duct drainage or a resection of a variable amount of the gland itself. DUVALshowed that caudal pancreaticojejunostomy was an effective treatment for simple dilatation of the pancreatic duct associated with chronic pancreatitis. However, multiple dilatations with stricturing of the duct system is the more common finding and PEUSTOW and GILLESBY3 therefore advocated a longitudinal filleting of the gland with invagination of the tail of the pancreas into a Roux loop. This required an extensive and tedious retroperitoneal dissection with mobilisation of the gland and removal of the spleen. Their operation has therefore been modified, so that a side-to-side pancreaticojejunostomy is fashioned after unroofing of the whole pancreatic duct in situ and direct anastomosis to a split Roux loop of jejunum. This type of procedure has the twin advantages of being technically straightforward and of preserving as much functioning parenchyma as possible. The disadvantages are also twofold. Firstly, the disease smoulder on in the residuum of the pancreatic tissue; and, secondly, the procedure is applicable only in those cases where the duct of Wirsung is dilated. The problems surrounding pancreatic can
Lloyd, J. R. J pediat. Surg. 1969, 4, 77. Touloukian, R. J., Posch, J. N., Spencer, R. ibid. 1972, 7, 194. Rogers, A. F., Dunn, P. M. Lancet, 1969, ii, 1246. Hillman, L. S., Goodwin, S. L., Sherman, W. R. New Engl. J. Med. 1975, 292, 381. 25. Book, L. S., Herbst, J. J., Jung, A. L. J. Pediat. 1976, 89, 463. 26. Barlow, B., Santulli, T. V., Heird, W. C., Pitt, J., Blanc, W. A., Schullinger, J. N. J. pediat. Surg. 1974, 9, 587. 27. Pitt, J., Barlow, B., Heird, W. C., Santulli, T. V. Pediat. Res. 1974, 8, 384. 28. Speer, M. E., Taber, L. H., Yow, M.D., Rudolph, A. J., Urteaga, J., Waller, S J. Pediat. 1976, 89, 91. 29. Stein, H., Beck, J., Solomon, A., Schmaman, A. Br. med. J. 1972, ii, 616. 30. Pedersen, P. V., Hansen, F. H., Halveg, A. B., Christiansen, E. D., Justesen, T., Hogh, P. Lancet, 1976, ii, 715.
21 22. 23. 24.
resection are both technical and metabolic. In general terms, total pancreatectomy is very rarely indicated for a benign condition: either proximal 1. 2. 3.
James, O., Agnew, J. E., Bouchier, I. A. D. Br. med. J. 1974, ii, 34. DuVal, M. K. Ann. Surg. 1954, 140, 775. Peustow, C. B. Gillesby, W. J. Arch Surg. 1958, 76, 898.
venous
Necrotising Enterocolitis enterocolitis, a serious condition of newborn infants, presents with vomiting, abdominal distension, and passage of blood in the stools; NECROTISING
radiological signs of gas in the bowel wall-pneumatosis intestinalis. In advanced cases the infant is shocked and may have septicaemia and peritonitis; an abdominal X-ray may then show free gas in the peritoneum or portal tract. At laparand there
are
otomy or necropsy there is ischaemic necrosis of the bowel wall, often widespread, with sloughing of the intestinal mucosa.1The first series of cases of necrotising enterocolitis (N.E.C.) were reported from the Babies Hospital, New York, in 1964 and
1965, although individual
cases
indistinguishable
in retrospect from N.E.c. had been recorded.3 4 Over the past ten years the condition has become progressively more common (or has been recognised more widely) in special-care baby units throughout the world.12 5-7 In some units a fivefold increase in incidence has been reported.6 8 Apparently there are striking differences in the incidence of the disease from country to country, from city to city, and even between neonatal units within the same city. The Royal Free Hospital, London, is at present coping with a major outbreak. N.E.C. predominantly affects infants of low birthweight who have been under intensive care; 1-4 in one series9 the frequency below 1200 g was as high as 27%. Infants of very low birthweight under intensive care have in common such factors as birth
asphyxia, hyaline-membrane disease, feeding by nasogastric or nasoduodenal tube, and umbilical arterial catheterisation. N.E.C. is not, however, confined to low-birth weight infants. It has been reported also among heavier infants who have undergone exchange blood-transfusions via umbilical
catheters.10-12 Among 26 cases of N.E.C. fol-
lowing exchange transfusion the mean birthweight was 2700 g.12 Low-birthweight infants tend to acquire N.E.c. in the first few days after birth (in two large series half of the cases had presented within five days of birth7) and the mortality-rate has ranged from around 30%13-15 to zin what seem to be comparable series; the disorder most commonly affects the terminal ileum,16 but it may extend to one or more areas of the large or small bowel or be even more widespread-producing in effect a gastroenterocolitis. In infants who acquire N.E.C. after exchange transfusion the onset is later, the mortality around 20%, and the colon more often affected than other sites in the gastrointestinal tract. 12 N.E.C. (or a condition which seems identical pathologically) has also been reported among infants with primary anatomical lesions of the bowel such as Hirschsprung’s disease, 2and among term infants with congenital heart-disease and primary infective gastroenteritis.111 Treatment of N.E.C. is based on experience rather than experiment. Umbilical catheters are removed, gastrointestinal feeds withheld, the stomach aspirated, fluids given by peripheral infusion, and broad-spectrum antibiotics administered. In infants who settle down on such medical treatment, early reintroduction of feeds has seemingly led to recurrence of the signs ofN.E.C., including pneumatosis intestinalis.7 19 Some workers recommend that the bowel be rested for up to ten days after the initial signs of the disorder have remitted.7 19 In the event of peritonitis, perforation, or a rapid decline in the infant’s condition prompt laparotomy is indicated with resection of the ischaemic segment and construction of an ileostomy or colostomy.1 2 14 15 BELL and others 14 claim that survival-rates improved in low-birthweight infants when kanamycin, at twice the normal parenteral dose, was given through a nasogastric tube. EGAN et a1.,20 in a controlled prospective trial of prophylactic alimentary kanamycin 15 mg/kg/day, have reported prevention of N.E.C. among low-birthweight infants believed to be at risk. However, the numbers in this study were too small for a firm conclusion to be drawn: there were no cases of N.E.C. among the 35 treated infants compared with 5 cases among 40 control infants.
1
Santulli, T. V., Schullinger, J. N., Heird, W. C., Gongaware, R. D., Wigger, J, Barlow, B., Blanc, W. A., Berdon, W. E. Pediatrics, 1975, 55, 376. 2. Dudgeon, D. L., Coran, A. G., Lauppe, F. A., Hodgman, J. E., Rosenkrantz, J. G. J. pediat. Surg. 1973, 8, 607. 3 Berdon, W. E., Grossman, H., Baker, D. H., Mizrahi, A., Barlow, O., Blanc, W. A Radiology, 1964, 83, 879. 4. Mizrahi, A., Barlow, O., Berdon, W., Blanc, W. A., Silverman, W. A. J. Pediat. 1965, 66, 697. 5 Hopkins, G. B., Gould, V. E., Stevenson, J. K., Oliver, T. K. Am. J. Dis. Child 1970, 120, 229. 6 Virnig, N. L., Reynolds, J. W. Am. J. Dis. Child. 1974, 128, 186. 7 Frantz, I. D., Litteureux, P., Engel, R. R., Hunt, C. E.J. Pediat. 1975, 86, 259.
Heese, H. de V. in Intensive Care in the Newborn (edited by L. Stern, B. Friis-Hansen, and P. Kildeberg); p. 73. New York, 1976. 9. Book, L S., Herbst, J. J., Atherton, S. O., Jung, A. L. J. Pediat. 1975, 87, 8.
602.
10. Corkery, J. J., Dubowitz, V., Lister, J., Moosa, A. Br. med. J. 1968, iv, 345. 11. Orme, R. L’E., Eades, S. M. ibid. p. 349. 12. Hardy, J. D., Savage, T. R. Am. J. Dis. Child. 1972, 124, 136. 13. Stevenson, J. K., Graham, C. B., Oliver, T. K., Goldenberg, V. E. Am. J. Surg. 1969, 118, 260. 14. Bell, M. J., Kosloske, A. M., Benton, C., Martin, L. W. J. pediat. Surg.
1973, 8, 601. 15. De Luca, F. G., 16. Touloukian, R.
Wesselhoeft, C. W. Am. J. Surg. 1974, 127, 410. J., Berdon, W. E., Amoury, R. A., Santulli, T. V. J. pediat. Surg. 1967, 2, 389. 17. Bill, A. H., Jr., Chapman, N. D. Am. J. Surg. 1962, 103, 70. 18. Polin, R. A., Pollock, P. F., Barlow, B., Wigger, H. J., Slovis, T. L., Santulli, T. V., Heird, W. C. J. Pediat. 1976, 89, 460. 19. Vollman, J. H., Smith, W. L., Tsang, R. C. J. Pediat. 1976, 88, 486. 20. Egan, E. A., Mantilla, G., Nelson, R. M., Eitzman, D. V. ibid. 1976, 89, 467.
460
Although the cause of N.E.C. is not established, the primary event does seem to be ischaemia of the bowel wall, followed by bacterial invasion, proliferation, and gas formation within the bowel wall. One suggestion,21 which is supported by experiments on asphyxiated newborn piglets,22 is that asphyxia leads to redistribution of cardiac output with reflex constriction of the intestinal vasculature and thence mucosal ischaemia. While this may be the case among low-birthweight infants, in larger infants affected after exchange transfusion the mechanism is probably different. Perhaps pressure changes in the umbilical venous catheter are transmitted through the portal venous system directly affecting mesenteric blood-flow.lU-12 Then there is the suggestion of ROGERS and DUNN23 that the increased incidence of N.E.C. was related to the introduction into neonatal intensive care of polyvinylchloride catheters and feeding-tubes and that the leaching out of plasticisers from P.v.c. produced a toxic disorder of vascular tone in the bowel wall. Lately HiLLMAN and colleagues24 reported substantial concentrations of plasticiser in segments of bowel resected at operation from infants with N.E.C. Other workers believe that gastrointestinal feeding is to blame, relating N.E.C. to high volumes of milk formula25 and to hyperosmolar elemental feeds9-although how such practices might lead to intestinal ischxmia remains to be explained. BARLOW and co-workers26 report that fresh breast milk protects newborn rats against N.E.c., suggesting that humoral or cellular components27 of the fresh milk may confer a passive enteric immunity to direct bacterial invasion. These are exciting observations. In other series the clustering of cases associated with outbreaks of gastroenteritis,18 sometimes due to non-enteropathogenic strains of Escherichia coli,z Salmonella,29 and Clostridia,3u has suggested a primary infective disorder. The various theories do agree that bacterial invasion is an essential step in the development of N.E.C. This does not explain why such a serious disorder should be increasing in incidence in special-care baby units. Maybe it is part of the price we pay for increasing survival of low-birthweight infants. However, those working in intensive-care units must remain vigilant in case N.E.c. represents a new iatrogenic disorder caused by some change in clinical practice.
Surgical Treatment in Chronic Relapsing Pancreatitis CHRONIC relapsing pancreatitis is uncommon in the United Kingdom. Half the cases are secondary to alcoholism;in the remainder the cause is usually obscure-only rarely is the chronic condition a sequel to acute pancreatitis. For most patients the main requirement is supervision and control of their endocrine and exocrine insufficiency, but there are a few who benefit from surgical treatment. Some need operation to relieve obstructive jaundice, or to control haematemesis resulting from splenic-vein thrombosis, or to deal with one of the complications of chronic pancreatitis such as pseudocyst formation or duodenal stenosis, but much the commonest indication for surgery is the severe and crippling pain which may otherwise lead the patient into drug dependence and addiction.
Operations on a healthy biliary tract, notably sphincteroplasty, convey little benefit and, like the nerve-cutting operations, splanchnicectomy and caeliac ganglionectomy, have few advocates nowadays. The nerve-cutting procedures relieve pancreatic pain in about a third of cases but the effect seldom lasts more than a couple of years, while the underlying disease process in the gland is in no way influenced. The operations now in common use are either some form of pancreatic-duct drainage or a resection of a variable amount of the gland itself. DUVALshowed that caudal pancreaticojejunostomy was an effective treatment for simple dilatation of the pancreatic duct associated with chronic pancreatitis. However, multiple dilatations with stricturing of the duct system is the more common finding and PEUSTOW and GILLESBY3 therefore advocated a longitudinal filleting of the gland with invagination of the tail of the pancreas into a Roux loop. This required an extensive and tedious retroperitoneal dissection with mobilisation of the gland and removal of the spleen. Their operation has therefore been modified, so that a side-to-side pancreaticojejunostomy is fashioned after unroofing of the whole pancreatic duct in situ and direct anastomosis to a split Roux loop of jejunum. This type of procedure has the twin advantages of being technically straightforward and of preserving as much functioning parenchyma as possible. The disadvantages are also twofold. Firstly, the disease smoulder on in the residuum of the pancreatic tissue; and, secondly, the procedure is applicable only in those cases where the duct of Wirsung is dilated. The problems surrounding pancreatic can
Lloyd, J. R. J pediat. Surg. 1969, 4, 77. Touloukian, R. J., Posch, J. N., Spencer, R. ibid. 1972, 7, 194. Rogers, A. F., Dunn, P. M. Lancet, 1969, ii, 1246. Hillman, L. S., Goodwin, S. L., Sherman, W. R. New Engl. J. Med. 1975, 292, 381. 25. Book, L. S., Herbst, J. J., Jung, A. L. J. Pediat. 1976, 89, 463. 26. Barlow, B., Santulli, T. V., Heird, W. C., Pitt, J., Blanc, W. A., Schullinger, J. N. J. pediat. Surg. 1974, 9, 587. 27. Pitt, J., Barlow, B., Heird, W. C., Santulli, T. V. Pediat. Res. 1974, 8, 384. 28. Speer, M. E., Taber, L. H., Yow, M.D., Rudolph, A. J., Urteaga, J., Waller, S J. Pediat. 1976, 89, 91. 29. Stein, H., Beck, J., Solomon, A., Schmaman, A. Br. med. J. 1972, ii, 616. 30. Pedersen, P. V., Hansen, F. H., Halveg, A. B., Christiansen, E. D., Justesen, T., Hogh, P. Lancet, 1976, ii, 715.
21 22. 23. 24.
resection are both technical and metabolic. In general terms, total pancreatectomy is very rarely indicated for a benign condition: either proximal 1. 2. 3.
James, O., Agnew, J. E., Bouchier, I. A. D. Br. med. J. 1974, ii, 34. DuVal, M. K. Ann. Surg. 1954, 140, 775. Peustow, C. B. Gillesby, W. J. Arch Surg. 1958, 76, 898.
