- Email: [email protected]
Colonic stenosis in the newborn: The possible thromboembolic etiology of intestinal stenosis and atresia
Colonic Stenosis in the Newborn : The Possible Thromboembolic
Etiology
of Intestinal
Stenosis and Atresia By JOHN MORSE ERSKINE HE INCIDENCE OF CONGENITAL ATRESIA AND STENOSIS OF THE INTESTINE has been estimated as in one in 20,000 births by Webb and Wangensteenl and one in 1500 births by Evans.2 Occurrence of these lesions in the colon estimated from figures derived from several large series is between 1.8 and 15 per cent. Colonic stenosis is much rarer than the atresia, and the lesions are about equally divided between those proximal and distal to the splenic flexure of the colon. Sometimes the terminal ileum is also involved. Rectal and anal atresias are generally not classified as a form of colonic atresia. Sturim” reviewed the 49 cases of congenital atresia or stenosis of the colon reported up to 1966 and reported an additional case. Nine more cases surviving treatment have been reported,4-s and another successfully treated patient with a stenosis from the distal transverse colon to the distal sigmoid is the subject of this report.
T
CASE REPORT The patient, a 5 lb., 14 oz. Caucasian boy, was born on June 8, 1967. He was full term and the 36-year-old mother’s pregnancy and delivery were considered normal. There was no hydramnios. No meconium was passed during the first two days of life: he became somewhat distended and vomited a small amount of gastric juice several times. Digital examination of the rectum showed a normal anal canal and rectal ampulla, but the upper part of the rectum seemed somewhat narrow. An X-ray examination showed gas in the stomach, small intestine and probably in the cecum, but not in the sigmoid. A barium enema was attempted, filling the rectal pouch and also a narrowed distal sigmoid at which point an obstruction to the flow of barium was encountered (Figs. 1, 2). The preoperative diagnosis of atresia of the distal colon was made, and at laparotomy, 56 hours after birth, he had distention of the small bowel and a very dilated, thick-walled, meconium-filled cecum and transverse colon. In the distal transverse colon, close to the splenic flexure, there was an abrupt transition from the dilated colon 2.5 cm. in diameter to a very narrow cordlike segment 0.5 cm. in diameter. This firm cord extended down to the pelvic area, beyond which point it was not examined. A biopsy specimen of the wall of this abnormal colon was taken down to, but not including, what was considered to be a central fibrous core of mucous membrane. A loop of transverse colon at the site of the obstruction was then brought out on to the abdominal wall, and the abdomen was closed. The following day the colon was opened, and a biopsy of bowel wall at the site of the colostomy was taken. The postoperative course was uneventful, and the patient was discharged from the hospital 29 days after birth with a well-functioning colostomy. Microscopic examination of the wall of the cordlike left colon showed rather thin but otherwise unremarkable muscular layers with small and shrunken ganglion cells between From the Department of Surgery, Children’s Hospital and Adult Medical Center, Francisco; and the University of California Medical School, San Francisco, California. JOHN MORSE ERSKINE, M.D.: Assistant Clinical Professor of Surgery, University California Medical School, San Francisco, California.
San
JOURNALOF PEDIATRICSURGERY,VOL. 5, No. 3 (JUNE), 1970
321
of
322
JOHN
MORSE
ERSKINE
Fig. l.-Flat film of abdomen two days after birth and after attempted barium enema. There is gas in stomach and small intestine, and gas and meconium in cecum and hepatic flexure of colon. There is also some barium in rectum.
the two muscle layers. There were larger and much-more-prominent ganglion cells together with hypertrophied muscle in the wall of the colon at the colostomy site. The child did well following discharge from the hospital. He had no significant problems with the colostomy, and at the age of 15 months, at which time he weighed approximately 18 pounds, he was considered to be ready for further surgery. At this time the little finger could be inserted into the rectum for its full length without encountering narrowing of the bowel lumen. A barium enema showed that the lumen of the rectum and rectosigmoid was probably normal. From the distal sigmoid proximally to the colostomy site the lumen was extremely narrow but nonetheless present so that barium did pass out of the distal colostomy opening (Fig. 3). At the second operation on October 1, 1968, the transverse colostomy was removed, and the entire cordlike left colon was excised from the colostomy site to the distal sigmoid colon. The bowel measured 0.5 cm. in diameter and 16 cm. in length. The sigmoid colon looped upon itself, and these loops were densely adherent to each other, suggesting an old inflammatory process in that area. No significant vessels were encountered while removing this segment of abnormal colon. However, one white fibrotic strand of tissue passing to a very narrow area of the sigmoid colon may have represented a sigmoidal artery and vein, although it seemed fibrotic and did not have the normal elasticity or color of an artery and vein. Unfortunately, a segment of this fibrous strand was not taken for microscopic
COLONIC STENOSIS IN THE NEWBORN
323
Fig. 2. Bauium enema two days after birth shows filling only of rectal ampula, narrowed distal signnoid, and obstruction to flow of barium at that Eboint.
examination. The diameter of the distal sigmoid colon was approximately 1 cm. with a thin and rather fibrous wall, and it was at this level that the end of the transverse colon, with a diameter of 2.5 cm. was anastomosed in two layers to the end and side of the sigmoid colon. There was some concern about the adequacy of the blood supply to the distal colon at the site of anastomosis; no bleeding was noted when the bowel was divided and incised longitudinally during the anastomosis, and the tissue was relatively avascular as compared to the completely normal transverse colon. The first stool was passed on the third postoperative day, and thereafter he had semiformed or loose movements at rather regular intervals. On the 10th postoperative day a small intraperitoneal abscess lateral to the area of anastomosis was diagnosed and drained under local anesthesia. A smail fecal fistula subsequently developed at that site which closed spontaneously prior to the patient’s discharge from the hospital. Since discharge he has been well, has gained weight and has no gastrointestinal problems. The segment of stenotic colon that was removed measured 18.5 cm. in length and 0.4 to 0.6 cm. in diameter. The narrowest area was in the center of the specimen, and in several areas the wall was very thin. Ganglion cells were present in the myenteric plexus, but in certain areas the cellularity was decreased. The mucosa was normal. There was nothing to suggest congenital megacolon. The microscopic diagnosis was hypoplasia of the colon with stenosis.
DISCUSSION The etiology of atresia and stenosis of the intestine in the newborn has been the subject of much discussion and considerable clinical, pathological and experimental investigation. The theory that it represents an enbryonal malformation due to a lack of recanalization of the intestinal tube at the
324
JOHN
MORSE
ERSKINE
Fig. 3.-Barium enema at 1.5 months of age showing normal rectum and rectosigmoid and stenosis from distal sigmoid to colostomy stoma in transverse colon.
end of the second month of fetal life9 has recently been questioned. A number of reports have presented evidence that many of the defects develop after the 1 lth or 12th week of fetal life and well beyond the period of development of the intestinal tube. This estimate is based on the evidence presented by Santulli and BlanclO that gross meconium or microscopic squamous epithelial cells, Lanugo hair, and bile droplets are found in the intestinal lumen at points distal to the atresia, and they must have arrived there through the mouth and from the liver after canalization has occurred. Bile is produced by the liver about the 11th week of fetal life and swallowing of vernix caseosa starts in the 12th week. Santulli and Blanc noted also, that microscopic examinations of the bowel in the area of atresia appeared to represent phases in the process of injury and repair of the bowel in that area. From these observations, they concluded that these intestinal defects represent the results of injury or accident to the fetal intestine rather than an embryonal malformation. What trauma or injury might be responsible for the atresia or stenosis has been the subject of speculation and experimentation. Volvulus, pinching of the intestine or its mesentery at the fetal umbilical ring, intussusception, focal
COLONIC
STENOSIS
IN THE NEWBORN
325
perforation of the bowel from local inflammation or muscular defects, and interference with the mesenteric blood supply have been mentioned as possible causes of at least some of the defects. If these theories are correct, it is also reasonable to assume that the injury or accident does not always occur at the same time in fetal life, and the gross and microscopic findings of these segments of intestine removed after birth tend to substantiate this hypothesis.lO It is possible that some of these defects which are recognized at birth or appear in the very early neonatal period may be the result of throboembolic episodes from the placenta, or, following birth, from the ligated umbilical vein. Intestinal lesions that appear to have developed at the time of, or shortly following birth, may yield some evidence to support this theory, and for that reason four cases of intestinal stenosis developing in the early neonatal period will be presented in some detail. A male infant 7% weeks old had a laparotomy at the San Francisco Children’s Hospital in 1968 because of failure to thrive and episodes of diarrhea and vomiting which started three weeks following birth. He had received an exchange transfusion on the second and fourth days of life because of erythroblastosis fetalis. After two hospital admissions for evaluation and attempts to control his frequent, green, foul-smelling, loose stools, and his increased spitting and vomiting, and after he failed to respond to change in diet, he was transferred to the Children’s Hospital weighing 11 ounces less than his birth weight of 6 lbs., 14 ounces. He was not distended at the time of admission, but he became so after a few days in the hospital. A barium enema and an upper gastrointestinal series showed that the rectum and sigmoid were dilated, the lumen in the mid-descending colon was 1.5 cm. in diameter, and just proximal to that area, the colon measured 3 cm. in diameter (Fig. 4). Some distention of the proximal colon and small bowel was also noted. At operation, a narrow segment of descending colon, approximately 6-cm. long, was removed; in one area, the diamenter was 0.9 cm. while most of the narrow segment measured 2 cm. in diameter. The colon proximal to this area measured 4.5 cm. in diameter. The mucous membrane in the narrowest area was granular, hyperemic and eroded, and on microscopic examination this proved to be an ulcerated area with extension of the ulceration in places into the muscular layers of the bowel wall. Granulation tissue containing plasma cells and lymphocytes was present. There was fibrosis of the serosal layer, particularly in the region of the mesenteric vessels. The artery and vein in the specimen were otherwise unremarkable. Vessels in the root of the mesentery were not removed with the specimen. Ganglion cells were present in the myenteric plexus. The findings were considered to be compatible with subtotal infarction of a portion of the large bowel. The changes of ulceration, fibrosis and stenosis were probably of at least four weeks’ duration, and the initial injury may have occurred at birth, 58 days before, or shortly thereafter following one of the two exchange transfusions. The changes seemed too active and acute to have developed during the prenatal period. At the time of surgery, a colostomy was made at the level of the proximal
326
JOHN
MORSE
ERSKINE
Fig. 4.-Barium study in 52-day-old infant showing incomplete intestinal obstruction and area of stenosis in descending colon.
descending colon, and when the infant was four months old normal continuity of the colon was successfully reestablished. The question arises whether this defect in the left colon was the result of an acute vascular occlusion of the left colic or the inferior mesenteric artery. A thrombus in the umbilical vein may have been dislodged during an exchange transfusion and may have embolized through the ductus venosus, the right side of the heart, the ductus arteriosus, and the aorta to lodge in the left colic artery or the inferior mesenteric artery. Ischemia of the segment of colon supplied by the occluded vessel could have led to necrosis of the mucosa with ulceration and local infection and fibrosis of the outer layers of the bowel and ultimately secondary stenosis. The patent artery and vein found close to the resected bowel could have been supplied by the superior mesenteric and the middle hemorrhoidal and perhaps the sigmoidal arteries, and if this embolic theory is correct, this collateral arterial circulation presumably was sufficient to. assure survival of the bowel segment without full thickness necrosis of the bowel wall, but it was not sufficient to prevent necrosis of the mucosa and inner layers of the bowel wall. Another possibility is that the stenosis was present at birth, was asymptomatic for the first three weeks, and then, when ulceration of the mucosa in the stenotic segment occurred, symptoms of incomplete intestinal obstruction developed. If this was the case,
COLONIC
STENOSIS
IN THE NEWBORN
321
the deep, rather extensive ulceration in the stenotic segment is not easily explained. It would seem more reasonable to postulate that the whole process started as a result of an embolic episode associated with the exchange transfusions following birth though necrotizing enterocolitis, a condition of obscure etiology, must also be considered. Additional evidence to support the concept that an acute arterial occlusion, possibly embolic, is responsible may be gained from the autopsy findings on a nine-week-old male twin reported by Gribetz and Strauss.ll The infant was well until one week of age when he began to have scanty bowel movements; five days later he developed distention, fecal vomiting, and dehydration which required four days in the hospital. Soon thereafter he developed intermittent diarrhea and was admitted to the hospital at seven weeks of age. He failed to respond to dietary alterations, parenteral fluids, transfusion and antibiotics. He continued to have four to six loose stools a day and ultimately died in a malnourished condition. At autopsy a segment of ileum measuring 15 cm. long was markedly stenotic with rigid, leathery walls. The mucosa was granular, red, and without the normal folds. The bowel above and below this area was normal. Microscopic examination of this segment showed that the mucosa was replaced by highly vascular granulation tissue, and the muscularis mucosa was destroyed. The muscularis propria was present, but there was some atrophy and fibrosis. There was fibrous thickening in the serosal layer. An occasional small vessel showed adventitial proliferation and narrowing of the lumen by the development of connective tissue. Serial sections through the mesentery showed patent vessels except those sectioned in the two tissue blocks closest to the root of the mesentery; here a medium-sized artery was occluded by a completely organized thrombus showing partial recanalization. The walls of the vessels were not structurally altered nor was there evidence of arteritis in the area of occlusion. The veins were patent. The conclusion was that the ileal lesion was the result of incomplete infarction, the collateral circulation preventing complete necrosis, and the significant tissue loss was in the metabolically active mucosa. Strauss concluded that the vascular occlusion probably occurred postnatally, and postulated that it resulted from volvulus on the 12th day of life which then subsided spontaneously causing incomplete segmented infarction of the bowel. No twist in the mesentery of the small bowel was found at autopsy. The findings in the stenotic segment of ileum are not unlike those in the colon segment of the infant of almost the same age that has just been presented and discussed. In this instance, however, additional mesentery was attainable because an autopsy rather than an operation was performed, and a definite arterial occlusion was found to be present. Rather than vo1vu1us, which was not demonstrated at autopsy, the initating cause might well have been an arterial embolus, at, or soon following birth, from the umbilical vein, possibly in association with monochorial placentation in this twin who was born second. The ischemic changes from the embolus could have led to the obstructive symptoms that developed on the 12th day of life when bacterial invasion of the necrotic mucosa occurred with associated inflammatory edema of the deeper layers of the bowel wall and narrowing of the lumen. In spite of the mesenteric arterial occlusion,
328
JOHN
MORSE
ERSKINE
necrosis of all layers of the bowel wall did not occur, and there was evidence of some repair of the injury to the bowel wall at the time of death. Freeman6 also had two patients with stenosis of the left colon in whom the initial symptoms developed in the neonatal period. The first patient was six weeks old when she developed loose stools containing blood mucus. The symptoms persisted until the child was 17 weeks old, at which time a stricture was discovered 7 cm. from the anus. Dilatations from below resulted in perforation of the colon on the seventh attempt, and an emergency colostomy had to be performed. The stricture had not been excised at the time the case was reported. The second patient was a premature baby who weighed 2 Ibs., 9 oz. at birth and had loose, foul-smelling stools 13 weeks after birth. After three weeks of incomplete intestinal obstruction, operation was performed, and stenosis was found at the junction of the descending and sigmoid colon. The resected segment of colon showed changes suggestive of perforation of the colon with secondary peritonitis and fibrosis and subsequent stenosis with stercoral ulceration and inflammation of the bowel segment. Though this patient died postoperatively, there was no mention of an autopsy or studies on the mesenteric vessels supplying the stenotic colonic segment. It was not stated whether fluids or blood were administered to this very premature infant by the umbilical vein following birth. Both these patients, however, like the ones described above, developed diarrhea a few weeks after birth. The author gave no explanation of the cause of the stenosis, but the description of the specimen removed in the second case suggests that an injury occurred about the time of birth. Again, one wonders if it could not have been an embolus from the umbilical vein leading to occlusion of the mesenteric artery. Several adult cases have been reported in which an embolus to a branch of the superior mesenteric artery has resulted in cicatrization and stenosis of a segment of small intestine. Rosenman and Gropper12 reported a patient who had had a myocardial infarction followed a little later by several emboli, one of which produced abdominal symptoms. Development of symptoms of intestinal obstruction 11 weeks following this episode led to the resection of a short, stenotic segment of small intestine which had a thick, indurated mesentery with no pulsating vessels in it. The mucosa of this scarred stricture was ulcerated and thin. The serosa was replaced by heavy granulation tissue. Occlusion of the mesenteric vessel by an embolus was later demonstrated at autopsy. Rosenemphasized that the mucosa, the layer which is metaman and GroppeP bolically most active, suffered most severely with ulceration and slough as a result of a degree of ischemia insufficient to cause complete necrosis of the muscularis and serosa. The chronic ulceration and associated local infection in turn contributed to the cicatrical stenosis that develops. He postulated that the intramural collateral vessels may prevent full thickness necrosis in a short loop of intestine deprived of the blood flow through its mesenteric vessel. Hawkins13 reported a patient with a similar history and findings. The findings in these cases are very similar to those in the infants with stenotic lesions. Bowel ischemia of a more-marked degree will result in gangrene and perforation of the bowel rather than stenosis. Corkery14 reported four patients in whom perforation of the colon followed exchange transfusions for hemolytic
COLONIC
STENOSIS
IN THE NEWBORN
329
disease of the newborn. The number of transfusions varied between one and four, all deteriorated within 24 to 48 hours after the transfusion procedure and all were explored by the eighth day of life. Three had perforations of the left colon with varying degrees and extent of necrosis of the antimesenteric wall of the neighboring bowel, and one had a perforation of the cecum. All survived the surgery. In all the segments of bowel removed, the necrosis progressed from involvement of only the mucosa to areas of involvement of all layers of the bowel wall. Mild inflammation was present together with extravasation of red blood cells. In three, passage of blood with the meconium four to 15 hours after the transfusion was the first sign followed by deterioration of the patient with the findings of abdominal distention and free air in the peritoneal cavity on X-ray examination of the abdomen. Corkeryl-’ postulated portal vein spasm or a retrograde portal vein embolus with sudden occlusion of a segment of that vein as a nossible explanation of the colonic perforation. Ormel” also reported six patients who developed bowel perforations a few days following exchange transfusions for hemolytic disease of the newborn, and he reported an additional patient with spontaneous bowel perforation following prolonged intravenous fluids administered through the umbilical vein. The clinical findings and course were very similar to those described by Corkery,li all had colonic perforations involving either the right, transverse, or left colon and in one, the small intestine had two areas of necrosis as well. Two patients died. Hypotension during the transfusion and local vasomotor disturbances were offered as an explanation for these perforations with bowel necrosis. Reference was made to three other cases (Refs. 15, 16,and 17) of spontaneous perforation following exchange transfusions. Thomas’” also included these three cases in his review of 26 cases of colon perforation of obscure etiology in infants. Again in these patients with colonic perforation following exchange transfusion, it would seem that a possible etiology would be an embolus arising in the umbilical vein and dislodged by the catheterization of that vein which then passes by way of the ductus venosus and the ductus arteriosus to a mesenteric artery. The question does arise as to whether some of the cases referred to in this discussion are not due to necrotizing enterocolitis which occurs in infants and involves bowel changes such as mucosal ulceration, necrosis of the intestinal wall, pseudomembrane formation, pneumatosis intestinalis and perforation. Wilson,‘o Touloukian,*l and Rabinowitz,32 in their recent papers on this subject, while admitting that the pathogenesis was unknown, offered several suggestions as to the possible etiology of this variable clinical condition. Much more work will be required to determine more precisely the cause or causes of these intestinal problems in the newborn and whether they arise as a result of general hypoxia during birth, bacterial invasion through the intestinal mucosa. a localized Schwartzman reaction, or possibly, in some cases at least, emboli to the mesenteric arteries. It has been recognized for many years that arterial occlusions do occur in the newborn. Miller et al.,“” reported an infant who died 33 hours after a normal delivery; at autopsy, gangrene of the intestine supplied by the superior
330
JOHN
MORSE
ERSKINE
mesenteric artery was found. An organized blood clot in the aorta extended into and occluded the lumen of the superior mesenteric artery. The origin of the embolus was not determined. Ratner and Swenson,24 and De Muth25 also reported cases of arterial occlusion in the newborn. Rothschild et a1.26reported a jaundiced infant who died on the sixth day of life with gangrene of almost all the small bowel; a firm, pinkish thrombus was found in its superior mesenteric artery. The ductus arteriosus was patent, and the heart was normal. No comment was made about the liver, the cause of jaundice, or the origin of the thrombus. Emboli from the umbilical vein to the mesenteric artery and to the hepatic branches of the portal vein or the hepatic artery is a possible explanation of both of the defects. Gross2? reported six cases of his own and 41 additional cases from the literature of arterial embolism and thrombosis in infancy. In this group infarction or gangrene involved the lower extremity in 28, the upper extremity in 13, the lung in four, the kidney in four, the brain in two, the scalp in one, the mesenteric vessels in three, and other areas in four. Sixty-nine per cent of these arterial occlusions were clinically apparent within the first 10 days of life, and the vast majority were noted within the first two to three weeks of life. Half of the patients died. Though the origin of the arterial occlusion was usually obscure, trauma during birth, infection, embolism from a congenital heart defect, and clotting abnormalities have all been implicated though in most cases the evidence of these factors were minimal or nonexistent. In one of Gross’s patients, the emboli seemed to arise from a thrombus in a very large ductus arteriosus, while in another, he suggested that progressive thrombosis in the umbilical arteries had ultimately led to thrombosis in the iliac arteries and finally the aorta. Arterial embolization can occur in the newborn infant or in the first week or two of neonatal life, and emboli do lodge in the mesenteric vessels leading to gangrene of a segment of bowel if the collateral circulation is inadequate. If collateral circulation is sufficient to prevent full thickness necrosis, there is good evidence that stenosis of that segment of bowel will ultimately develop. Though it is difficult if not impossible to obtain irrefutable evidence that in the newborn without a congenital heart defect the source of these emboli is the umbilical vein, nonetheless, it is reasonable to postulate that the thrombosis of the umbilical vein after birth can lead to a free floating thrombus at its junction with the left hepatic vein which, in turn, may embolize going either to the liver or through the ductus arteriosus to the arterial circulation generally distal to the ductus, but perhaps, on occasions, even to the left carotid and subclavian arteries. It is difficult to obtain evidence as to developments in the prenatal period leading to the defects such as intestinal atresia or stenosis that are discovered at birth. Certain parallel situations and mechanisms may exist between the early neonate and the fetus. The theory of an embolic etiology of intestinal stenosis and atresia may apply to the prenatal period with differences based largely on the fact that the fetus is in a sterile environment, and the gastrointestinal tract is not functioning as a digestive unit. The theory of an embolic etiology of at least some of the atresias and stenoses which occur may be
COLONIC STENOSIS
IN THE NEWBORN
331
based on the development of thrombophlebitis in the collecting venous channels of the placenta with propagation of the thrombosis in the slowly flowing venous blood of the umbilical vein and ultimately, embolization from the umbilical vein through the ductus venosus, the vena cava, the right ventricle, pulmonary artery, ductus arteriosus and the aorta to one of its branches. In the case reported in this paper, the extensive stenosis of the colon supplied by the inferior mesenteric artery may have resulted from ischemia short of gangrene of that segment of bowel with survival depending on the collateral circulation that ultimately took over to prevent necrosis. The narrowed distal sigmoid used in the anastomosis seemed fibrotic and thin and although its color was considered normal, there was no oozing or active arterial bleeding when the bowel was opened suggesting diminished vascularity. The fibrous strand which was observed extending directly to the wall of the stenotic, fibrotic and adherent sigmoid loop was not pulsating and did not look like a normal artery and vein, and no significant, functioning arteries were encountered in removing the stenotic segment of colon. The blind proximal and distal ends in jejunoileal atresias have been shown to have diminished blood supply in a high percentage of the cases.lO Vascular accident as a cause of stenosis and atresia has been considered by many who are interested in this entity. Barnard and Louw~~~“~ligated one or more mesenteric vessels or created a strangulated volvulus in dog fetuses of 45 to 55 days gestation. Of the 80 per cent that were born alive, all had either stenosis or atresia of the intestine. Stenosis resulted from incomplete obstruction of the mesenteric vessel, and the more extensive forms of atresia resulted from ligation of the mesenteric vessel close to its origin. The devascularized segment had disintegrated and was completely absorbed in some dogs while a fibrous remnant remained in others. Laufman et a130 demonstrated that autolysis of a devascularized, sterile, strangulated intestinal segment could occur intraperitoneally without fetal morbidity or mortality. This resorption of necrotic tissue in the fetus is undoubtedly related to the sterility of the intestine during gestation. Louw”l noted a high incidence of meconium peritonitis, omphalocele, or malfixation of the mesentery in his patients with atresia or stenosis of the small bowel. Volvulus of the distal collapsed bowel was noted in 33 per cent of his cases of jejunoileal occlusions. He concluded that the frequency of excessive mobility of the cecum and ascending colon may be intimately related to the pathogenesis of these intestinal lesions because of the torsion and occlusion that can occur in the mesenteric vessels. It does seem as though this may be the cause in many of these patients. In many patients there is no evidence of previous volvulus or other mechanical injuries to the bowel or its mesentery, and in these cases an embolus to a mesenteric artery might result in intestinal stenosis or atresia. Stenoses and atresias in the duodenal and rectal areas probably arise in a different manner than those in the jejunoiliac and colic areas. There is no mesentery in the duodenal area by the 1 lth week and the rectum, derived from the cloaca, never had a mesentery. Mechanical events such as volvulus are not likely to involve these areas, and because of the good collateral
332
JOHN MORSE ERSKINE
circulation, embolic episodes would be unlikely to produce ischemic changes in these areas of the intestine. There is also evidence that the theory of failure of recanalization of the intestine during early fetal development may apply to these two areas but not to the jejunoiliac and colic areas.QJ2 The high incidence of mongoloids and other extraabdominal congenital abnormalities in the cases with duodenal atresia and the low incidence in those with jejunoiliac and colic atresias29 is also evidence that the former may represent an earlier developmental defect and the latter a defect that arises later in intrauterine life and often associated with intraabdominal abnormalities such as malrotation. Additional clincial research is needed and should include careful microscopic studies of the mesenteric arteries of infants dying as a result of atresia or stenosis of the small or large intestine. The placenta should also be studied in detail in all cases in which atresia or stenosis is discovered, and additional information may thus be obtained regarding the theory that is presented here that thrombophlebitis in the placenta may occasionally result in an embolus to a mesenteric artery, and ultimately this may result in atresia or stenosis of the bowel supplied by that vessel. SUMMARY
A neonate with stenosis of the descending and sigmoid colon was successfully treated by a transverse colostomy on the second day of life, and a resection of the stenotic bowel with anastomosis 15 months later. It is postulated that this defect, as well as atresias and stenoses in other areas of the jejunum, ileum, and colon may, in some cases at least, arise as a result of an arterial embolus originating in an area of thrombophlebitis in the placenta and passing by way of the umbilical vein, the ductus venosus, the ductus arteriosus, and the aorta to a mesenteric artery supplying a segment of the small or large bowel. Depending on the degree of local tissue ischemia, stenosis or atresia results. To support this theory as to the etiology of this defect, indirect clinical evidence is drawn from the newborn where stenoses or bowel necrosis with perforation may occur, particularly in the neonate receiving an exchange transfusion. A case of a newborn who developed a stenosis of the colon after two exchange transfusions is presented in detail, and other examples of stenosis or bowel necrosis and perforation reported are discussed based on the hypothesis that in these cases also, the primary course is again an arterial embolus arising in the neonate from a propagating thrombus in the umbilical vein which breaks off, or is broken off, and passes through the ductus venosus, the right heart, the ductus arteriosus and the aorta to occlude a mesenteric artery. If bowel ischemia without full thickness necrosis results, stenosis will ultimately develop; if full thickness necrosis results, perforation will occur. Such arterial emboli may be the primary problem behind at least some of the cases of necrotizing enterocolitis in the newborn. REFERENCES 1. Webb, C. H., and Wangensteen, Congenital intestinal atresia. Amer. Child. 41: 262-284, 193 1.
0. H.: J. Dis.
2. Evans, C. H.: Atresias of the gastrointestinal tract. Int. Abstracts Surg. Gynec. Obstet. 92: l-8, 1951.
COLONIC
STENOSIS
IN THE NEWBORN
3. Sturim, H. S., and Temberg, .I. L.: Congenital atresia of the colon. Surg. 59: 458-464, 1966. 4. Peck, D. A., Lynn, H. B., and Harris, L. E.: Congenital atresia and stenosis of the colon. Arch. Surg. 87:428-439, 1963. 5. Lee, Sae Soon, Kim, Kil Yung, and Hong, Pill Whoon: Congenital atresia of the colon. J.A.M.A. 202: 1148-l 150, 1967. 6. Freeman, N. V.: Congenital atresia and stenosis of the colon. Brit. J. Surg. 53:595-599, 1966. 7. Gathe, J. C., Banfield, E. H., and Roett, C. J.: Congenital atresia of the colon. A simple one stage method of repair. Amer. Surg. 30:271-275, 1964. 8. Marion, J., Picault, C., Michel, C. Ii., Lapras, A., and Daudet, M.: Some remarks about four atresias of the colon. Ann. Chir. Infant 6:233-239, 1965. 9. Patten, B. M.: Textbook of Human Embryology. Philadelphia, Blakiston, 1946. 10. Santulli, T. V.. and Blanc, W. A.: Congenital atresia of the intestine: pathogenesis and treatment. Ann. Surg. 154:939948, 1961. 11. Gribetz. D., and Strauss, L.: Clinical Pathological Conference (The Mount Sinai Hospital, New York). J. Pediat. 73:629-637, 1968. 12. Rosenman, L. D., and Gropper, A. N.: Small intestinal stenosis caused by infarction; An unusual sequel of mesenteric artery embolism. Ann. Surg. 141:2.5&262, 19.55. 13. Hawkins, C. F.: Jejunal stenosis following mesenteric artery occlusion. Lancet 2: 121-122, 1957. 14. Corkery, J. J., Dubowitz, V., Lister, J., and Moosa, A.: Colonic perforation after exchange transfusion. Brit. Med. J. 4:345349, 1968. 15. Orme. R. L., and Eades, S. M.: Perforation of the bowel in the newborn as a complication of exchange transfusion. Brit. Med. J. 4:349-351, 1968. 16. Nienhuis, L. I.: Colon perforations in the newborn. Amer. Surg. 29: 835-840, 1963. 17. Waldhausen, J. A., Herendeen T., and King, H.: Necrotizing colitis of the newborn: Common cause of perforation of the colon. Surg. 54~365-372, 1963. 18. Hermann, R. F.: Perforation of the colon from necrotizing colitis in the new-
333 born: Report of a survival and a new etiologic concept. Surg. 58:436-441, 1965. 19. Thomas, C. S., Jr., and Brockman. S. K.: Idiopathic perforation of the colon in infancy: Report of two cases and literature review. Ann. Surg. 164:853-858, 1966. 20. Wilson, S. E., and Woolley, M. M.: Primary necrotizing enterocolitin in infants. Arch. Surg. 99:563-566, 1969. 21. Touloukian, R. J., Berdon, W. E., Amoury, R. A., and Santulli, T. V.: Surgical experience with necrotizing enterocolitis in the infant. J. Ped. Surg. 2:389-401. 1967. 22. Rabinowitz, J. G., Wolf, B. S., Feller, M. R., and Krasna, I.: Colonic changes following necrotizing enterocolitis in the newborn. Amer. J. Roentgen. 103:359-365, 1968. 23. Miller, W. H., and Maioriello, J. J., and Stein, 0. B., Jr.: Mesenteric vascular occlusion in infancy and childhood. J. Pediat. 59:567-570, 1961. 24. Ratner, I. A., and Swenson, 0.: Mesenteric vascular occlusion in infancy and childhood. New Eng. J. Med. 263: 11221125, 1960. 25. DeMuth, W. E.: Mesenteric vascular occlusion in children. J.A.M.A. 179: 130133, 1962. 26. Rothschild, H. B., Storck, A., and Myers, B.: Mesenteric occlusion in a newborn infant. J. Pediat. 43:569-572, 1953. 27. Gross, R. E.: Arterial embolism and thrombosis in infancy. Amer. J. Dis. Child 70:61-73, 1945. 28. Barnard, C. N., and Louw, J. H.: The genesis of intestinal atresia. Minnesota Med. 39~745-753, 1956. 29. Louw, .I. H.: Investigations into the etiology of congenital atresia of the colon. Dis. Colon Rectum 7:471-478, 1964. 30. Laufman, H., Martin, W. B., Method, H.. Tuell, S. W., and Harding, H.: Observations in strangulation obstruction. II. The fate of sterile devascularized intestine in the peritoneal cavity. Arch. Surg. 59: 5.50-564, 1949. 31. Louw, J. H.: Jejunoileal atresia and stenosis. J. Ped. Surg. 1:8-23, 1966. 32. Lynn, H. B., and Espinas, E. E.: Intestinal atresia: An attempt to relate location to embryologic processes. Arch. Surg. 79:357-361, 1959.
Etiology
of Intestinal
Stenosis and Atresia By JOHN MORSE ERSKINE HE INCIDENCE OF CONGENITAL ATRESIA AND STENOSIS OF THE INTESTINE has been estimated as in one in 20,000 births by Webb and Wangensteenl and one in 1500 births by Evans.2 Occurrence of these lesions in the colon estimated from figures derived from several large series is between 1.8 and 15 per cent. Colonic stenosis is much rarer than the atresia, and the lesions are about equally divided between those proximal and distal to the splenic flexure of the colon. Sometimes the terminal ileum is also involved. Rectal and anal atresias are generally not classified as a form of colonic atresia. Sturim” reviewed the 49 cases of congenital atresia or stenosis of the colon reported up to 1966 and reported an additional case. Nine more cases surviving treatment have been reported,4-s and another successfully treated patient with a stenosis from the distal transverse colon to the distal sigmoid is the subject of this report.
T
CASE REPORT The patient, a 5 lb., 14 oz. Caucasian boy, was born on June 8, 1967. He was full term and the 36-year-old mother’s pregnancy and delivery were considered normal. There was no hydramnios. No meconium was passed during the first two days of life: he became somewhat distended and vomited a small amount of gastric juice several times. Digital examination of the rectum showed a normal anal canal and rectal ampulla, but the upper part of the rectum seemed somewhat narrow. An X-ray examination showed gas in the stomach, small intestine and probably in the cecum, but not in the sigmoid. A barium enema was attempted, filling the rectal pouch and also a narrowed distal sigmoid at which point an obstruction to the flow of barium was encountered (Figs. 1, 2). The preoperative diagnosis of atresia of the distal colon was made, and at laparotomy, 56 hours after birth, he had distention of the small bowel and a very dilated, thick-walled, meconium-filled cecum and transverse colon. In the distal transverse colon, close to the splenic flexure, there was an abrupt transition from the dilated colon 2.5 cm. in diameter to a very narrow cordlike segment 0.5 cm. in diameter. This firm cord extended down to the pelvic area, beyond which point it was not examined. A biopsy specimen of the wall of this abnormal colon was taken down to, but not including, what was considered to be a central fibrous core of mucous membrane. A loop of transverse colon at the site of the obstruction was then brought out on to the abdominal wall, and the abdomen was closed. The following day the colon was opened, and a biopsy of bowel wall at the site of the colostomy was taken. The postoperative course was uneventful, and the patient was discharged from the hospital 29 days after birth with a well-functioning colostomy. Microscopic examination of the wall of the cordlike left colon showed rather thin but otherwise unremarkable muscular layers with small and shrunken ganglion cells between From the Department of Surgery, Children’s Hospital and Adult Medical Center, Francisco; and the University of California Medical School, San Francisco, California. JOHN MORSE ERSKINE, M.D.: Assistant Clinical Professor of Surgery, University California Medical School, San Francisco, California.
San
JOURNALOF PEDIATRICSURGERY,VOL. 5, No. 3 (JUNE), 1970
321
of
322
JOHN
MORSE
ERSKINE
Fig. l.-Flat film of abdomen two days after birth and after attempted barium enema. There is gas in stomach and small intestine, and gas and meconium in cecum and hepatic flexure of colon. There is also some barium in rectum.
the two muscle layers. There were larger and much-more-prominent ganglion cells together with hypertrophied muscle in the wall of the colon at the colostomy site. The child did well following discharge from the hospital. He had no significant problems with the colostomy, and at the age of 15 months, at which time he weighed approximately 18 pounds, he was considered to be ready for further surgery. At this time the little finger could be inserted into the rectum for its full length without encountering narrowing of the bowel lumen. A barium enema showed that the lumen of the rectum and rectosigmoid was probably normal. From the distal sigmoid proximally to the colostomy site the lumen was extremely narrow but nonetheless present so that barium did pass out of the distal colostomy opening (Fig. 3). At the second operation on October 1, 1968, the transverse colostomy was removed, and the entire cordlike left colon was excised from the colostomy site to the distal sigmoid colon. The bowel measured 0.5 cm. in diameter and 16 cm. in length. The sigmoid colon looped upon itself, and these loops were densely adherent to each other, suggesting an old inflammatory process in that area. No significant vessels were encountered while removing this segment of abnormal colon. However, one white fibrotic strand of tissue passing to a very narrow area of the sigmoid colon may have represented a sigmoidal artery and vein, although it seemed fibrotic and did not have the normal elasticity or color of an artery and vein. Unfortunately, a segment of this fibrous strand was not taken for microscopic
COLONIC STENOSIS IN THE NEWBORN
323
Fig. 2. Bauium enema two days after birth shows filling only of rectal ampula, narrowed distal signnoid, and obstruction to flow of barium at that Eboint.
examination. The diameter of the distal sigmoid colon was approximately 1 cm. with a thin and rather fibrous wall, and it was at this level that the end of the transverse colon, with a diameter of 2.5 cm. was anastomosed in two layers to the end and side of the sigmoid colon. There was some concern about the adequacy of the blood supply to the distal colon at the site of anastomosis; no bleeding was noted when the bowel was divided and incised longitudinally during the anastomosis, and the tissue was relatively avascular as compared to the completely normal transverse colon. The first stool was passed on the third postoperative day, and thereafter he had semiformed or loose movements at rather regular intervals. On the 10th postoperative day a small intraperitoneal abscess lateral to the area of anastomosis was diagnosed and drained under local anesthesia. A smail fecal fistula subsequently developed at that site which closed spontaneously prior to the patient’s discharge from the hospital. Since discharge he has been well, has gained weight and has no gastrointestinal problems. The segment of stenotic colon that was removed measured 18.5 cm. in length and 0.4 to 0.6 cm. in diameter. The narrowest area was in the center of the specimen, and in several areas the wall was very thin. Ganglion cells were present in the myenteric plexus, but in certain areas the cellularity was decreased. The mucosa was normal. There was nothing to suggest congenital megacolon. The microscopic diagnosis was hypoplasia of the colon with stenosis.
DISCUSSION The etiology of atresia and stenosis of the intestine in the newborn has been the subject of much discussion and considerable clinical, pathological and experimental investigation. The theory that it represents an enbryonal malformation due to a lack of recanalization of the intestinal tube at the
324
JOHN
MORSE
ERSKINE
Fig. 3.-Barium enema at 1.5 months of age showing normal rectum and rectosigmoid and stenosis from distal sigmoid to colostomy stoma in transverse colon.
end of the second month of fetal life9 has recently been questioned. A number of reports have presented evidence that many of the defects develop after the 1 lth or 12th week of fetal life and well beyond the period of development of the intestinal tube. This estimate is based on the evidence presented by Santulli and BlanclO that gross meconium or microscopic squamous epithelial cells, Lanugo hair, and bile droplets are found in the intestinal lumen at points distal to the atresia, and they must have arrived there through the mouth and from the liver after canalization has occurred. Bile is produced by the liver about the 11th week of fetal life and swallowing of vernix caseosa starts in the 12th week. Santulli and Blanc noted also, that microscopic examinations of the bowel in the area of atresia appeared to represent phases in the process of injury and repair of the bowel in that area. From these observations, they concluded that these intestinal defects represent the results of injury or accident to the fetal intestine rather than an embryonal malformation. What trauma or injury might be responsible for the atresia or stenosis has been the subject of speculation and experimentation. Volvulus, pinching of the intestine or its mesentery at the fetal umbilical ring, intussusception, focal
COLONIC
STENOSIS
IN THE NEWBORN
325
perforation of the bowel from local inflammation or muscular defects, and interference with the mesenteric blood supply have been mentioned as possible causes of at least some of the defects. If these theories are correct, it is also reasonable to assume that the injury or accident does not always occur at the same time in fetal life, and the gross and microscopic findings of these segments of intestine removed after birth tend to substantiate this hypothesis.lO It is possible that some of these defects which are recognized at birth or appear in the very early neonatal period may be the result of throboembolic episodes from the placenta, or, following birth, from the ligated umbilical vein. Intestinal lesions that appear to have developed at the time of, or shortly following birth, may yield some evidence to support this theory, and for that reason four cases of intestinal stenosis developing in the early neonatal period will be presented in some detail. A male infant 7% weeks old had a laparotomy at the San Francisco Children’s Hospital in 1968 because of failure to thrive and episodes of diarrhea and vomiting which started three weeks following birth. He had received an exchange transfusion on the second and fourth days of life because of erythroblastosis fetalis. After two hospital admissions for evaluation and attempts to control his frequent, green, foul-smelling, loose stools, and his increased spitting and vomiting, and after he failed to respond to change in diet, he was transferred to the Children’s Hospital weighing 11 ounces less than his birth weight of 6 lbs., 14 ounces. He was not distended at the time of admission, but he became so after a few days in the hospital. A barium enema and an upper gastrointestinal series showed that the rectum and sigmoid were dilated, the lumen in the mid-descending colon was 1.5 cm. in diameter, and just proximal to that area, the colon measured 3 cm. in diameter (Fig. 4). Some distention of the proximal colon and small bowel was also noted. At operation, a narrow segment of descending colon, approximately 6-cm. long, was removed; in one area, the diamenter was 0.9 cm. while most of the narrow segment measured 2 cm. in diameter. The colon proximal to this area measured 4.5 cm. in diameter. The mucous membrane in the narrowest area was granular, hyperemic and eroded, and on microscopic examination this proved to be an ulcerated area with extension of the ulceration in places into the muscular layers of the bowel wall. Granulation tissue containing plasma cells and lymphocytes was present. There was fibrosis of the serosal layer, particularly in the region of the mesenteric vessels. The artery and vein in the specimen were otherwise unremarkable. Vessels in the root of the mesentery were not removed with the specimen. Ganglion cells were present in the myenteric plexus. The findings were considered to be compatible with subtotal infarction of a portion of the large bowel. The changes of ulceration, fibrosis and stenosis were probably of at least four weeks’ duration, and the initial injury may have occurred at birth, 58 days before, or shortly thereafter following one of the two exchange transfusions. The changes seemed too active and acute to have developed during the prenatal period. At the time of surgery, a colostomy was made at the level of the proximal
326
JOHN
MORSE
ERSKINE
Fig. 4.-Barium study in 52-day-old infant showing incomplete intestinal obstruction and area of stenosis in descending colon.
descending colon, and when the infant was four months old normal continuity of the colon was successfully reestablished. The question arises whether this defect in the left colon was the result of an acute vascular occlusion of the left colic or the inferior mesenteric artery. A thrombus in the umbilical vein may have been dislodged during an exchange transfusion and may have embolized through the ductus venosus, the right side of the heart, the ductus arteriosus, and the aorta to lodge in the left colic artery or the inferior mesenteric artery. Ischemia of the segment of colon supplied by the occluded vessel could have led to necrosis of the mucosa with ulceration and local infection and fibrosis of the outer layers of the bowel and ultimately secondary stenosis. The patent artery and vein found close to the resected bowel could have been supplied by the superior mesenteric and the middle hemorrhoidal and perhaps the sigmoidal arteries, and if this embolic theory is correct, this collateral arterial circulation presumably was sufficient to. assure survival of the bowel segment without full thickness necrosis of the bowel wall, but it was not sufficient to prevent necrosis of the mucosa and inner layers of the bowel wall. Another possibility is that the stenosis was present at birth, was asymptomatic for the first three weeks, and then, when ulceration of the mucosa in the stenotic segment occurred, symptoms of incomplete intestinal obstruction developed. If this was the case,
COLONIC
STENOSIS
IN THE NEWBORN
321
the deep, rather extensive ulceration in the stenotic segment is not easily explained. It would seem more reasonable to postulate that the whole process started as a result of an embolic episode associated with the exchange transfusions following birth though necrotizing enterocolitis, a condition of obscure etiology, must also be considered. Additional evidence to support the concept that an acute arterial occlusion, possibly embolic, is responsible may be gained from the autopsy findings on a nine-week-old male twin reported by Gribetz and Strauss.ll The infant was well until one week of age when he began to have scanty bowel movements; five days later he developed distention, fecal vomiting, and dehydration which required four days in the hospital. Soon thereafter he developed intermittent diarrhea and was admitted to the hospital at seven weeks of age. He failed to respond to dietary alterations, parenteral fluids, transfusion and antibiotics. He continued to have four to six loose stools a day and ultimately died in a malnourished condition. At autopsy a segment of ileum measuring 15 cm. long was markedly stenotic with rigid, leathery walls. The mucosa was granular, red, and without the normal folds. The bowel above and below this area was normal. Microscopic examination of this segment showed that the mucosa was replaced by highly vascular granulation tissue, and the muscularis mucosa was destroyed. The muscularis propria was present, but there was some atrophy and fibrosis. There was fibrous thickening in the serosal layer. An occasional small vessel showed adventitial proliferation and narrowing of the lumen by the development of connective tissue. Serial sections through the mesentery showed patent vessels except those sectioned in the two tissue blocks closest to the root of the mesentery; here a medium-sized artery was occluded by a completely organized thrombus showing partial recanalization. The walls of the vessels were not structurally altered nor was there evidence of arteritis in the area of occlusion. The veins were patent. The conclusion was that the ileal lesion was the result of incomplete infarction, the collateral circulation preventing complete necrosis, and the significant tissue loss was in the metabolically active mucosa. Strauss concluded that the vascular occlusion probably occurred postnatally, and postulated that it resulted from volvulus on the 12th day of life which then subsided spontaneously causing incomplete segmented infarction of the bowel. No twist in the mesentery of the small bowel was found at autopsy. The findings in the stenotic segment of ileum are not unlike those in the colon segment of the infant of almost the same age that has just been presented and discussed. In this instance, however, additional mesentery was attainable because an autopsy rather than an operation was performed, and a definite arterial occlusion was found to be present. Rather than vo1vu1us, which was not demonstrated at autopsy, the initating cause might well have been an arterial embolus, at, or soon following birth, from the umbilical vein, possibly in association with monochorial placentation in this twin who was born second. The ischemic changes from the embolus could have led to the obstructive symptoms that developed on the 12th day of life when bacterial invasion of the necrotic mucosa occurred with associated inflammatory edema of the deeper layers of the bowel wall and narrowing of the lumen. In spite of the mesenteric arterial occlusion,
328
JOHN
MORSE
ERSKINE
necrosis of all layers of the bowel wall did not occur, and there was evidence of some repair of the injury to the bowel wall at the time of death. Freeman6 also had two patients with stenosis of the left colon in whom the initial symptoms developed in the neonatal period. The first patient was six weeks old when she developed loose stools containing blood mucus. The symptoms persisted until the child was 17 weeks old, at which time a stricture was discovered 7 cm. from the anus. Dilatations from below resulted in perforation of the colon on the seventh attempt, and an emergency colostomy had to be performed. The stricture had not been excised at the time the case was reported. The second patient was a premature baby who weighed 2 Ibs., 9 oz. at birth and had loose, foul-smelling stools 13 weeks after birth. After three weeks of incomplete intestinal obstruction, operation was performed, and stenosis was found at the junction of the descending and sigmoid colon. The resected segment of colon showed changes suggestive of perforation of the colon with secondary peritonitis and fibrosis and subsequent stenosis with stercoral ulceration and inflammation of the bowel segment. Though this patient died postoperatively, there was no mention of an autopsy or studies on the mesenteric vessels supplying the stenotic colonic segment. It was not stated whether fluids or blood were administered to this very premature infant by the umbilical vein following birth. Both these patients, however, like the ones described above, developed diarrhea a few weeks after birth. The author gave no explanation of the cause of the stenosis, but the description of the specimen removed in the second case suggests that an injury occurred about the time of birth. Again, one wonders if it could not have been an embolus from the umbilical vein leading to occlusion of the mesenteric artery. Several adult cases have been reported in which an embolus to a branch of the superior mesenteric artery has resulted in cicatrization and stenosis of a segment of small intestine. Rosenman and Gropper12 reported a patient who had had a myocardial infarction followed a little later by several emboli, one of which produced abdominal symptoms. Development of symptoms of intestinal obstruction 11 weeks following this episode led to the resection of a short, stenotic segment of small intestine which had a thick, indurated mesentery with no pulsating vessels in it. The mucosa of this scarred stricture was ulcerated and thin. The serosa was replaced by heavy granulation tissue. Occlusion of the mesenteric vessel by an embolus was later demonstrated at autopsy. Rosenemphasized that the mucosa, the layer which is metaman and GroppeP bolically most active, suffered most severely with ulceration and slough as a result of a degree of ischemia insufficient to cause complete necrosis of the muscularis and serosa. The chronic ulceration and associated local infection in turn contributed to the cicatrical stenosis that develops. He postulated that the intramural collateral vessels may prevent full thickness necrosis in a short loop of intestine deprived of the blood flow through its mesenteric vessel. Hawkins13 reported a patient with a similar history and findings. The findings in these cases are very similar to those in the infants with stenotic lesions. Bowel ischemia of a more-marked degree will result in gangrene and perforation of the bowel rather than stenosis. Corkery14 reported four patients in whom perforation of the colon followed exchange transfusions for hemolytic
COLONIC
STENOSIS
IN THE NEWBORN
329
disease of the newborn. The number of transfusions varied between one and four, all deteriorated within 24 to 48 hours after the transfusion procedure and all were explored by the eighth day of life. Three had perforations of the left colon with varying degrees and extent of necrosis of the antimesenteric wall of the neighboring bowel, and one had a perforation of the cecum. All survived the surgery. In all the segments of bowel removed, the necrosis progressed from involvement of only the mucosa to areas of involvement of all layers of the bowel wall. Mild inflammation was present together with extravasation of red blood cells. In three, passage of blood with the meconium four to 15 hours after the transfusion was the first sign followed by deterioration of the patient with the findings of abdominal distention and free air in the peritoneal cavity on X-ray examination of the abdomen. Corkeryl-’ postulated portal vein spasm or a retrograde portal vein embolus with sudden occlusion of a segment of that vein as a nossible explanation of the colonic perforation. Ormel” also reported six patients who developed bowel perforations a few days following exchange transfusions for hemolytic disease of the newborn, and he reported an additional patient with spontaneous bowel perforation following prolonged intravenous fluids administered through the umbilical vein. The clinical findings and course were very similar to those described by Corkery,li all had colonic perforations involving either the right, transverse, or left colon and in one, the small intestine had two areas of necrosis as well. Two patients died. Hypotension during the transfusion and local vasomotor disturbances were offered as an explanation for these perforations with bowel necrosis. Reference was made to three other cases (Refs. 15, 16,and 17) of spontaneous perforation following exchange transfusions. Thomas’” also included these three cases in his review of 26 cases of colon perforation of obscure etiology in infants. Again in these patients with colonic perforation following exchange transfusion, it would seem that a possible etiology would be an embolus arising in the umbilical vein and dislodged by the catheterization of that vein which then passes by way of the ductus venosus and the ductus arteriosus to a mesenteric artery. The question does arise as to whether some of the cases referred to in this discussion are not due to necrotizing enterocolitis which occurs in infants and involves bowel changes such as mucosal ulceration, necrosis of the intestinal wall, pseudomembrane formation, pneumatosis intestinalis and perforation. Wilson,‘o Touloukian,*l and Rabinowitz,32 in their recent papers on this subject, while admitting that the pathogenesis was unknown, offered several suggestions as to the possible etiology of this variable clinical condition. Much more work will be required to determine more precisely the cause or causes of these intestinal problems in the newborn and whether they arise as a result of general hypoxia during birth, bacterial invasion through the intestinal mucosa. a localized Schwartzman reaction, or possibly, in some cases at least, emboli to the mesenteric arteries. It has been recognized for many years that arterial occlusions do occur in the newborn. Miller et al.,“” reported an infant who died 33 hours after a normal delivery; at autopsy, gangrene of the intestine supplied by the superior
330
JOHN
MORSE
ERSKINE
mesenteric artery was found. An organized blood clot in the aorta extended into and occluded the lumen of the superior mesenteric artery. The origin of the embolus was not determined. Ratner and Swenson,24 and De Muth25 also reported cases of arterial occlusion in the newborn. Rothschild et a1.26reported a jaundiced infant who died on the sixth day of life with gangrene of almost all the small bowel; a firm, pinkish thrombus was found in its superior mesenteric artery. The ductus arteriosus was patent, and the heart was normal. No comment was made about the liver, the cause of jaundice, or the origin of the thrombus. Emboli from the umbilical vein to the mesenteric artery and to the hepatic branches of the portal vein or the hepatic artery is a possible explanation of both of the defects. Gross2? reported six cases of his own and 41 additional cases from the literature of arterial embolism and thrombosis in infancy. In this group infarction or gangrene involved the lower extremity in 28, the upper extremity in 13, the lung in four, the kidney in four, the brain in two, the scalp in one, the mesenteric vessels in three, and other areas in four. Sixty-nine per cent of these arterial occlusions were clinically apparent within the first 10 days of life, and the vast majority were noted within the first two to three weeks of life. Half of the patients died. Though the origin of the arterial occlusion was usually obscure, trauma during birth, infection, embolism from a congenital heart defect, and clotting abnormalities have all been implicated though in most cases the evidence of these factors were minimal or nonexistent. In one of Gross’s patients, the emboli seemed to arise from a thrombus in a very large ductus arteriosus, while in another, he suggested that progressive thrombosis in the umbilical arteries had ultimately led to thrombosis in the iliac arteries and finally the aorta. Arterial embolization can occur in the newborn infant or in the first week or two of neonatal life, and emboli do lodge in the mesenteric vessels leading to gangrene of a segment of bowel if the collateral circulation is inadequate. If collateral circulation is sufficient to prevent full thickness necrosis, there is good evidence that stenosis of that segment of bowel will ultimately develop. Though it is difficult if not impossible to obtain irrefutable evidence that in the newborn without a congenital heart defect the source of these emboli is the umbilical vein, nonetheless, it is reasonable to postulate that the thrombosis of the umbilical vein after birth can lead to a free floating thrombus at its junction with the left hepatic vein which, in turn, may embolize going either to the liver or through the ductus arteriosus to the arterial circulation generally distal to the ductus, but perhaps, on occasions, even to the left carotid and subclavian arteries. It is difficult to obtain evidence as to developments in the prenatal period leading to the defects such as intestinal atresia or stenosis that are discovered at birth. Certain parallel situations and mechanisms may exist between the early neonate and the fetus. The theory of an embolic etiology of intestinal stenosis and atresia may apply to the prenatal period with differences based largely on the fact that the fetus is in a sterile environment, and the gastrointestinal tract is not functioning as a digestive unit. The theory of an embolic etiology of at least some of the atresias and stenoses which occur may be
COLONIC STENOSIS
IN THE NEWBORN
331
based on the development of thrombophlebitis in the collecting venous channels of the placenta with propagation of the thrombosis in the slowly flowing venous blood of the umbilical vein and ultimately, embolization from the umbilical vein through the ductus venosus, the vena cava, the right ventricle, pulmonary artery, ductus arteriosus and the aorta to one of its branches. In the case reported in this paper, the extensive stenosis of the colon supplied by the inferior mesenteric artery may have resulted from ischemia short of gangrene of that segment of bowel with survival depending on the collateral circulation that ultimately took over to prevent necrosis. The narrowed distal sigmoid used in the anastomosis seemed fibrotic and thin and although its color was considered normal, there was no oozing or active arterial bleeding when the bowel was opened suggesting diminished vascularity. The fibrous strand which was observed extending directly to the wall of the stenotic, fibrotic and adherent sigmoid loop was not pulsating and did not look like a normal artery and vein, and no significant, functioning arteries were encountered in removing the stenotic segment of colon. The blind proximal and distal ends in jejunoileal atresias have been shown to have diminished blood supply in a high percentage of the cases.lO Vascular accident as a cause of stenosis and atresia has been considered by many who are interested in this entity. Barnard and Louw~~~“~ligated one or more mesenteric vessels or created a strangulated volvulus in dog fetuses of 45 to 55 days gestation. Of the 80 per cent that were born alive, all had either stenosis or atresia of the intestine. Stenosis resulted from incomplete obstruction of the mesenteric vessel, and the more extensive forms of atresia resulted from ligation of the mesenteric vessel close to its origin. The devascularized segment had disintegrated and was completely absorbed in some dogs while a fibrous remnant remained in others. Laufman et a130 demonstrated that autolysis of a devascularized, sterile, strangulated intestinal segment could occur intraperitoneally without fetal morbidity or mortality. This resorption of necrotic tissue in the fetus is undoubtedly related to the sterility of the intestine during gestation. Louw”l noted a high incidence of meconium peritonitis, omphalocele, or malfixation of the mesentery in his patients with atresia or stenosis of the small bowel. Volvulus of the distal collapsed bowel was noted in 33 per cent of his cases of jejunoileal occlusions. He concluded that the frequency of excessive mobility of the cecum and ascending colon may be intimately related to the pathogenesis of these intestinal lesions because of the torsion and occlusion that can occur in the mesenteric vessels. It does seem as though this may be the cause in many of these patients. In many patients there is no evidence of previous volvulus or other mechanical injuries to the bowel or its mesentery, and in these cases an embolus to a mesenteric artery might result in intestinal stenosis or atresia. Stenoses and atresias in the duodenal and rectal areas probably arise in a different manner than those in the jejunoiliac and colic areas. There is no mesentery in the duodenal area by the 1 lth week and the rectum, derived from the cloaca, never had a mesentery. Mechanical events such as volvulus are not likely to involve these areas, and because of the good collateral
332
JOHN MORSE ERSKINE
circulation, embolic episodes would be unlikely to produce ischemic changes in these areas of the intestine. There is also evidence that the theory of failure of recanalization of the intestine during early fetal development may apply to these two areas but not to the jejunoiliac and colic areas.QJ2 The high incidence of mongoloids and other extraabdominal congenital abnormalities in the cases with duodenal atresia and the low incidence in those with jejunoiliac and colic atresias29 is also evidence that the former may represent an earlier developmental defect and the latter a defect that arises later in intrauterine life and often associated with intraabdominal abnormalities such as malrotation. Additional clincial research is needed and should include careful microscopic studies of the mesenteric arteries of infants dying as a result of atresia or stenosis of the small or large intestine. The placenta should also be studied in detail in all cases in which atresia or stenosis is discovered, and additional information may thus be obtained regarding the theory that is presented here that thrombophlebitis in the placenta may occasionally result in an embolus to a mesenteric artery, and ultimately this may result in atresia or stenosis of the bowel supplied by that vessel. SUMMARY
A neonate with stenosis of the descending and sigmoid colon was successfully treated by a transverse colostomy on the second day of life, and a resection of the stenotic bowel with anastomosis 15 months later. It is postulated that this defect, as well as atresias and stenoses in other areas of the jejunum, ileum, and colon may, in some cases at least, arise as a result of an arterial embolus originating in an area of thrombophlebitis in the placenta and passing by way of the umbilical vein, the ductus venosus, the ductus arteriosus, and the aorta to a mesenteric artery supplying a segment of the small or large bowel. Depending on the degree of local tissue ischemia, stenosis or atresia results. To support this theory as to the etiology of this defect, indirect clinical evidence is drawn from the newborn where stenoses or bowel necrosis with perforation may occur, particularly in the neonate receiving an exchange transfusion. A case of a newborn who developed a stenosis of the colon after two exchange transfusions is presented in detail, and other examples of stenosis or bowel necrosis and perforation reported are discussed based on the hypothesis that in these cases also, the primary course is again an arterial embolus arising in the neonate from a propagating thrombus in the umbilical vein which breaks off, or is broken off, and passes through the ductus venosus, the right heart, the ductus arteriosus and the aorta to occlude a mesenteric artery. If bowel ischemia without full thickness necrosis results, stenosis will ultimately develop; if full thickness necrosis results, perforation will occur. Such arterial emboli may be the primary problem behind at least some of the cases of necrotizing enterocolitis in the newborn. REFERENCES 1. Webb, C. H., and Wangensteen, Congenital intestinal atresia. Amer. Child. 41: 262-284, 193 1.
0. H.: J. Dis.
2. Evans, C. H.: Atresias of the gastrointestinal tract. Int. Abstracts Surg. Gynec. Obstet. 92: l-8, 1951.
COLONIC
STENOSIS
IN THE NEWBORN
3. Sturim, H. S., and Temberg, .I. L.: Congenital atresia of the colon. Surg. 59: 458-464, 1966. 4. Peck, D. A., Lynn, H. B., and Harris, L. E.: Congenital atresia and stenosis of the colon. Arch. Surg. 87:428-439, 1963. 5. Lee, Sae Soon, Kim, Kil Yung, and Hong, Pill Whoon: Congenital atresia of the colon. J.A.M.A. 202: 1148-l 150, 1967. 6. Freeman, N. V.: Congenital atresia and stenosis of the colon. Brit. J. Surg. 53:595-599, 1966. 7. Gathe, J. C., Banfield, E. H., and Roett, C. J.: Congenital atresia of the colon. A simple one stage method of repair. Amer. Surg. 30:271-275, 1964. 8. Marion, J., Picault, C., Michel, C. Ii., Lapras, A., and Daudet, M.: Some remarks about four atresias of the colon. Ann. Chir. Infant 6:233-239, 1965. 9. Patten, B. M.: Textbook of Human Embryology. Philadelphia, Blakiston, 1946. 10. Santulli, T. V.. and Blanc, W. A.: Congenital atresia of the intestine: pathogenesis and treatment. Ann. Surg. 154:939948, 1961. 11. Gribetz. D., and Strauss, L.: Clinical Pathological Conference (The Mount Sinai Hospital, New York). J. Pediat. 73:629-637, 1968. 12. Rosenman, L. D., and Gropper, A. N.: Small intestinal stenosis caused by infarction; An unusual sequel of mesenteric artery embolism. Ann. Surg. 141:2.5&262, 19.55. 13. Hawkins, C. F.: Jejunal stenosis following mesenteric artery occlusion. Lancet 2: 121-122, 1957. 14. Corkery, J. J., Dubowitz, V., Lister, J., and Moosa, A.: Colonic perforation after exchange transfusion. Brit. Med. J. 4:345349, 1968. 15. Orme. R. L., and Eades, S. M.: Perforation of the bowel in the newborn as a complication of exchange transfusion. Brit. Med. J. 4:349-351, 1968. 16. Nienhuis, L. I.: Colon perforations in the newborn. Amer. Surg. 29: 835-840, 1963. 17. Waldhausen, J. A., Herendeen T., and King, H.: Necrotizing colitis of the newborn: Common cause of perforation of the colon. Surg. 54~365-372, 1963. 18. Hermann, R. F.: Perforation of the colon from necrotizing colitis in the new-
333 born: Report of a survival and a new etiologic concept. Surg. 58:436-441, 1965. 19. Thomas, C. S., Jr., and Brockman. S. K.: Idiopathic perforation of the colon in infancy: Report of two cases and literature review. Ann. Surg. 164:853-858, 1966. 20. Wilson, S. E., and Woolley, M. M.: Primary necrotizing enterocolitin in infants. Arch. Surg. 99:563-566, 1969. 21. Touloukian, R. J., Berdon, W. E., Amoury, R. A., and Santulli, T. V.: Surgical experience with necrotizing enterocolitis in the infant. J. Ped. Surg. 2:389-401. 1967. 22. Rabinowitz, J. G., Wolf, B. S., Feller, M. R., and Krasna, I.: Colonic changes following necrotizing enterocolitis in the newborn. Amer. J. Roentgen. 103:359-365, 1968. 23. Miller, W. H., and Maioriello, J. J., and Stein, 0. B., Jr.: Mesenteric vascular occlusion in infancy and childhood. J. Pediat. 59:567-570, 1961. 24. Ratner, I. A., and Swenson, 0.: Mesenteric vascular occlusion in infancy and childhood. New Eng. J. Med. 263: 11221125, 1960. 25. DeMuth, W. E.: Mesenteric vascular occlusion in children. J.A.M.A. 179: 130133, 1962. 26. Rothschild, H. B., Storck, A., and Myers, B.: Mesenteric occlusion in a newborn infant. J. Pediat. 43:569-572, 1953. 27. Gross, R. E.: Arterial embolism and thrombosis in infancy. Amer. J. Dis. Child 70:61-73, 1945. 28. Barnard, C. N., and Louw, J. H.: The genesis of intestinal atresia. Minnesota Med. 39~745-753, 1956. 29. Louw, .I. H.: Investigations into the etiology of congenital atresia of the colon. Dis. Colon Rectum 7:471-478, 1964. 30. Laufman, H., Martin, W. B., Method, H.. Tuell, S. W., and Harding, H.: Observations in strangulation obstruction. II. The fate of sterile devascularized intestine in the peritoneal cavity. Arch. Surg. 59: 5.50-564, 1949. 31. Louw, J. H.: Jejunoileal atresia and stenosis. J. Ped. Surg. 1:8-23, 1966. 32. Lynn, H. B., and Espinas, E. E.: Intestinal atresia: An attempt to relate location to embryologic processes. Arch. Surg. 79:357-361, 1959.