Keratoacanthoma: a deficient squamous cell carcinoma? Study of bcl-2 expression.

Ten keratoacanthomas with both proliferative and regressive histologic features along with 10 well-differentiated squamous cell carcinomas were examined using immunohistochemistry for the expression of bcl-2, a protooncogene recently recognized to be involved in protecting cells from undergoing apoptosis. The squamous cell carcinomas had a modest but diffuse staining pattern, while the proliferative keratoacanthomas stained only at the basal cells and only rare cells stained positively in the regressive keratoacanthomas. The degree and pattern of staining suggest a loss of bcl-2 expression with tumor maturity in keratoacanthoma and a possible role in their ultimate involution.

Bowel perforation with nonoperative treatment of meconium ileus.

Over the last 11 years, 22 neonates were treated with water-soluble contrast enemas to relieve the obstruction of meconium ileus. Fifteen babies had a gestational age of at least 36 weeks, and 16 weighed more than 2,500 g. All presented with clinical findings of a bowel obstruction, confirmed by roentgenograms, and each eventually had high sweat chloride levels. Each neonate had from 1 to 4 water-soluble contrast enemas administered slowly by syringe over 15 to 30 minutes. Eight enemas were successful in relieving the obstruction, four newborns requiring only one enema. Fourteen were unsuccessful, three having more than one enema. Seven of these 14 had intraabdominal pathology that would have required surgery. In five babies the bowel was perforated by the enema, the colon in three, and terminal ileum in two. These perforations were all immediately recognized during the course of the enema and operated on forthwith; a stoma was made in four cases. Only one of these five babies would have required an operation because of a volvulus. There were no fluid or electrolyte disturbances caused by the contrast material, and none of the babies with perforations died. Although this enema technique was successful in one third of cases, and despite the fact that perforations ensued in one quarter of cases, the procedure still seems warranted if the following precautions are taken: establishment of proper temperature, fluid, and electrolyte balance; the radiologist is not rushed, is extremely gentle, willing to repeat the study until no further progress is evident; the surgeon is available for an immediate laparotomy should a perforation occur.(ABSTRACT TRUNCATED AT 250 WORDS)

Twenty-one year experience with the pediatric gastric tube.

From 1964 to 1985 inclusive, gastric tubes have been constructed in 36 infants and children to replace a congenitally defective esophagus or an esophagus with acquired irreparable damage. This report reviews our entire series to date covering a 21-year experience. There were 24 boys and 12 girls ranging in age from 3 months to 17 years. Twenty-two patients were operated on because of congenital esophageal defects and 14 for acquired lesions. A proximally based antiperistaltic tube was constructed in 32 instances, and a distally based isoperistaltic tube made in four. Thirty tubes were passed retrosternally, five through the chest (four with an anastomosis) and one subcutaneously. Twenty-nine infants and children had their tube construction staged, and the remaining seven had the entire procedure done in one stage. The spleen was removed in 23 early gastric tube operations. There were 19 extratube major complications. Twenty-four gastric tube neck anastomoses leaked (66%); all but one closed spontaneously within 3 months. There were 15 esophagogastric tube neck anastomotic strictures (41%), which were dilated; nine required resection. Thirty-two of the 36 infants and children have been followed for more than 1 year. Twenty-nine are swallowing normally, one is still being dilated, and one infant still does not swallow well. Mild sacculation or tortuosity of the gastric tube has been encountered only one. Growth was slow in four until the school years. One boy had his improperly made tube eventually discarded for a colon replacement. There were three deaths (tracheostomy complication, aspiration, gastric tube ulcer hemorrhage). Despite the above problems, the eventual outcome continues to be satisfactory and satisfying.(ABSTRACT TRUNCATED AT 250 WORDS)

Stimulation of proteoglycan synthesis by fibroblastic cells in culture due to the addition of "matrigenin" from bovine bone.

Hyaluronic acid is the major glycosaminoglycan characteristically secreted in culture by human synovial fibroblastic cells, but stimulated proteoglycan synthesis, as well as hyaluronic acid synthesis, was observed when a partially purified factor from bovine bone, containing "matrigenin" activity, was added to these cells. Cultures were labelled with [35S]SO4 and [3H]glucosamine and the radioactive glycoconjugates were extracted from the medium under dissociative conditions. After a preliminary separation of the radioactive high molecular weight compounds, the proteoglycans were separated from hyaluronic acid and glycoproteins by ion-exchange chromatography in 8 M urea. The proteoglycan fraction from the fibroblastic cells, whose synthesis was stimulated by the "matrigenin" activity, contained at least two species, the lower molecular weight proteoglycan eluting in the range of 400-600 K under dissociative conditions during gel filtration chromatography.

"Matrigenin" activity from bovine bone--III. Effects on glycosaminoglycans and proteoglycans of human synovial cells in culture.

1. Human synovial fibroblastic cells were cultured in the presence and absence of an extract from bovine bone containing "matrigenin" activity. The rate of incorporation of radioactivity into the glycosaminoglycans of the medium of "matrigenin"-treated cultures increased after 24 hr of incubation, compared to "controls". 2. Higher serum concentrations had a greater effect on the incorporation of radioactivity into hyaluronic acid synthesized by "matrigenin"-treated cultures, than by "controls". 3. Incorporation of radioactive precursors into the proteoglycans isolated from the medium was greater in the "matrigenin"-treated cultures than in "controls". The synthesis of a large mol. wt proteoglycan was specifically stimulated.

Intussusception due to lymphoma.

Over 1,200 infants and children with an intussusception were treated at our hospital over the last 40 years and from this group, only 11 were found to have a lymphoma as a leading point for the intussusception. This number represents 17% of the 65 pathologic lesions that have caused an intussusception. Three children were under 41/2 years of age. All the children except two were chronically ill with pain for at least 1 week and usually for several months; weight loss and an abdominal mass in many instances provided the suspicion of a possible malignancy. When barium studies were done, there was almost always an ileocolic intussusception present with some obstruction. Reduction of the intussusception was accomplished with hydrostatic barium enema in 10 of the 11 patients; the one reduction, however, had a residual filling defect. Surgery confirmed the above findings and a resection of the leading point lymphoma was carried out in all of the children. In spite of all forms of treatment, death followed in all but three, usually within several months. One of these three survivors was treated with radiotherapy and steroids (after surgical excision) and is alive after 30 years; the second was also given chemotherapy and is alive and well after 6 years, and the third has not had radiotherapy and is alive after 10 months.

Uptake and incorporation of 14C-labelled carbohydrates in the tissues of the reproductive system of the female fowl.

The in vivo incorporation of radioactivity from [14C]GlcN, [14C]GalN, [14C]Glc and [14C]Gal, for different time intervals between 1 and 240 hr into whole tissues, acetone extracted tissues and MPS-P of the different parts of the reproductive system of the female fowl was studied. The incorporation of radioactivity was much more extensive when [14C]GlcN was injected than when [14C]GalN was injected. The incorporation of radioactivity was much more extensive when [14C]HexN was injected than when the corresponding [14C]Hex was injected. This difference of incorporation was greater in the MPS-P than in the fresh or acetone extracted tissues. A comparison was undertaken in the extent that radioactivity was incorporated among the different parts of the reproductive system of the fowl when [14C]HexN and 14C[Hex] were administered.

Comparative distribution of glycosaminoglycans and proteoglycans in the reproductive tissues of the female fowl.

The objective of this work was to survey and compare the composition of the parts of the reproductive system of the female fowl in glycosaminoglycans and proteoglycans. Those parts analyzed were ovary, infundibulum, magnum, isthmus, shell gland and vagina. Methods of analysis included cellulose acetate electrophoresis, infrared spectroscopy, colorimetry, amino acid determination and scanning electron microscopy. Concentrations of glycosaminoglycans were higher in vagina, ovary, infundibulum and isthmus than in shell gland and magnum. Glycosaminoglycans may be important in those parts of the reproductive tract which contribute membraneous and mucosal material to the descending egg, and where fertilization of the egg occurs.

The disappearance of free air after pediatric laparotomy.

The disappearance of intraperitoneal free air after pediatric laparotomy has been the subject of much talk and speculation, but little scientific publication. Moreover, there is no unanimous opinion as to the "correct" time of disappearance of such postoperative free air. Eighty-eight pediatric surgical patients ranging in age from newborn to 18 years were studied after each had a laparotomy to determine when the postoperative free intraabdominal air disappeared. Upright abdominal x-rays were taken in each patient starting on the second day after operation and these x-rays were repeated every few days until the free air was no longer visible. No more than eight such single upright abdominal x-rays were taken in any one patient, the majority having only two or three. Free air under the diaphragm(s) was the specific criterion followed until disappearance of the free air. At the time of the x-ray, the temperature was noted, as well as the presence or absence of the following: nasogastric suction, bowel sounds, flatus, stools, drains, and wound infection. The patients in this series fit into three distinct groups: all newborns and small infants had no free air seen on upright x-rays by the second postoperative day. The free air found in older infants and children operated on through small abdominal incisions (eg, McBurney) was gone in most by the third postoperative day, with the longest time being eight days.(ABSTRACT TRUNCATED AT 250 WORDS)

Neonatal intestinal pseudoobstruction.

In the past 10 years, the diagnosis of pseudoobstruction lasting more than two months was confirmed in 10 infants after sepsis, meconium ileus, and Hirschsprung's disease were excluded, and surgery or autopsy failed to demonstrate a site of mechanical intestinal obstruction. Four infants had undergone prior operation for another anomaly: gastroschisis (2) and ileal atresia (2). Five of the remaining infants also had megacystis. The lack of coordinated intestinal motility was best appreciated by radiocontrast small bowel studies, which showed degrees of aperistalsis or segmentation. Rectal manometric studies were not helpful. Histology of the intestine was normal in seven, while a gross deficiency of nerve fibres was noted in one patient and a myopathy of smooth muscle in another. A variety of drugs used to stimulate peristalsis were ineffective. Seven patients had 25 operations, often to exclude mechanical causes of obstruction. The mainstay of treatment was TPN and intestinal decompression. Six children survived; their ages ranged between 8 months and 9 years (median age, 16 months). There has been improvement in intestinal peristalsis in five children, three of whom now tolerate a regular diet and two of whom are on TPN and are currently increasing oral intake. Four infants died, two from sepsis, two from TPN-related hepatic failure. In contrast to previous reports, we conclude that intestinal pseudoobstruction may be self-limited in some neonates, including those with megacystis. Therapy should consist of long-term nutritional support and treatment of other anomalies that may be present.

Thirty years of experience with pediatric primary malignant liver tumors.

Since 1950, 48 infants and children from 10 weeks to 16 years of age presented with primary hepatic malignancy. Signs and symptoms ranged from asymptomatic to those of malignant disease. All patients had a palpable abdominal mass. Jaundice was seen in five patients, four of whom had preexisting cirrhosis. Three male children had evidence of precocious puberty. Whereas liver function tests were usually normal, alpha-fetoprotein levels, when elevated, proved useful diagnostically and as a tumor marker in follow-up. Hepatic angiography and computed tomography (CT) scans have provided the most valuable preoperative assessment of hepatic architecture. Sixteen infants and children underwent resection for cure. Eleven of these patients are alive and disease free 6 months to 23 years later. Six additional patients had incomplete resection with subsequent radiotherapy and/or chemotherapy; only one such patient is disease-free past 3 years. Twenty-six tumors could only be biopsied; most of these patients died within 12 months regardless of what treatment they received. The histology was hepatoblastoma in 39 patients, hepatocellular carcinoma in 4, fibrolamellar carcinoma in 4, and malignant mesenchymal tumor (mesenchymoma) in 1. The patients with hepatocellular carcinoma and mesenchymoma all died. Three of four patients with fibrolamellar carcinoma are alive and disease-free following resection up to 3 years; this histology seems favorable. The other survivors had hepatoblastoma. The role of adjunctive chemotherapy and/or radiotherapy has not yet been determined.

The problem of recurrent thyroglossal duct remnants.

The removal of a thyroglossal duct or sinus is a common pediatric surgical operation. It has been taught that if the duct remnant is removed down to and including the middle third of the hyoid bone, the "correct" operation has been done. The three authors have an experience totaling over 60 years in pediatric surgery during which time they operated on 270 thyroglossal duct cysts and sinuses. In this group were 27 recurrences of which three belonged to the authors. Most recurrent thyroglossal duct remnants were found to have the middle third of the hyoid bone still in place, and with its removal the patients were cured. However, during this period of time, there were thyroglossal duct cysts and sinuses which recurred in spite of the "correct" surgical procedure having been done. These patients had all been operated on between three and five times thus creating a difficult and unusual problem. The solution to these recurrent thyroglossal duct cysts and sinuses were deeper excisions to remove residual tracts deep to the previously removed hyoid bone, and/or wider excisions to excise previously missed respiratory epithelial remnants which deviated laterally from the midline. The latter tissue was found to be a more centrally directed branchial cleft sinus.

Carcinoid in a rectal duplication: a unique pediatric surgical problem.

Since 1935 at the Hospital for Sick Children in Toronto, 13 cases of carcinoid have been seen as incidental findings in the appendix, but carcinoids of the rectum have never previously been reported in childhood. The authors report a child with a rectal duplication in which this tumour was found. The rationale for local resection of the duplication with its contained carcinoid is understood in the light of the principles for treatment of intestinal carcinoids in general and carcinoids of the rectum in particular. Two years after operation the child is well without signs of local or systemic recurrence.

Traumatic diaphragmatic hernia in children.

Because of its rarity in children the diagnosis of diaphragmatic hernia due to trauma is often delayed, sometimes resulting in gastrointestinal or respiratory complaints or obstruction of the small intestine. Eleven children with rupture of the diaphragm were seen between 1950 and 1977. All injuries were due to blunt trauma sustained in automobile-related accidents; all involved the left hemidiaphragm. Nine children had associated injuries, most commonly fractures, and injury to the head and spleen. In six children the diaphragmatic rupture was recognized and treated at the time of injury. The other five presented with gastrointestinal or respiratory symptoms from 2 months to 3 years after the trauma. Repair was through the abdomen in 10 patients and the chest in 1. There was only one death from an associated severe craniocerebral injury. Complications developed in five surviving patients but were relatively minor.

An assessment of the surgical treatment of adhesive small bowel obstruction in infants and children.

At The Hospital for Sick Children, Toronto, Canada, adhesive small bowel obstruction (SBO) ranks seventh as a cause of pediatric bowel obstruction. Between January 1968 and December 1979, 131 infants and children had adhesive SBO proven at laparotomy or autopsy: 123 had 1; 7 had 16 adhesiotomies; 1 died without surgery; 100 had 1 prior operation; and 31 had multiple operations. Over 80% of the SBOs developed within 2 yr of the prior operations. Appendectomy and subtotal colectomy were the most common prior operation. Postoperative morbidity occurred in 29 children; 20 were observed longer than 24 hr before laparotomy. The rate of wound infection ranged from 4% to 50%; it was lowest for those children who had lysis of adhesions only, and highest for those who had lysis and decompressive enterotomy or perforation repair. Results indicate that delaying adhesiotomy and entering the GI tract during adhesiotomy are associated with increased morbidity (p less than 0.01), and therefore should be avoided. Prophylactic antibiotics may have a protective role during anterolysis.

Ruptured spleen--when to operate?

Sixty-three patients with splenic injuries were treated during a 5-yr period from 1974-1979. The decision to operate was based on the patient's clinical course, not on the presence of splenic injury alone. Those who were stable on admission or after initial resuscitation were treated nonoperatively. This consisted of strict bed rest, nasogastric suction, and i.v. fluids--including blood--as required. Those who bled massively were operated on promptly. At operation, the spleen was repaired if possible or excised if damaged beyond repair. Forty patients were treated nonoperatively. Sixteen of these required blood transfusions (mean 31.2 +/- 5.3 ml/kg). One patient in this group developed a large defect on spleen scan at 3 wk post injury. There was no other morbidity and no mortality following nonoperative treatment. Nineteen required operation all within 16 hr of admission. Fifteen underwent splenectomy, 2 partial splenectomy, and 1 splenorrhaphy. In 1 the bleeding had stopped. All required blood before operation (mean 80.4 +/- 10.1 ml/kg). Seven in this group died (6 from head injuries and 1 from bleeding). Thus surgery was avoided in 2 out of 3 and the spleen saved in 3 out of 4 patients with documented splenic injuries. We believe that where adequate facilities exist nonoperative treatment of splenic injuries is both safe and effective. When bleeding is massive from the beginning or replacement requirements exceed 40 ml/kg, operation is indicated.

Pseudocysts of the pancreas after blunt abdominal trauma in children.

Of 6 children with posttraumatic pancreatic pseudocyst, 5 had been transferred from other hospitals. Three of the 5 had undergone laparotomy but in only 1 had the pancreatic injury been noted. All 5 had elevated serum amylase activity on admission here, but in only 2 had this been measured in the referring hospital. Three were seriously ill at the time of transfer, and all 6 patients required prolonged hospitalization (1.3--5.5 mo). The lesion resolved spontaneously in 1, and was drained externally in 3 and by cystogastrostomy alone i 1. One child required multiple surgical procedures, terminating in subtotal pancreatectomy. The seriousness of this lesion demands constant alertness to the possibility of pancreatic pseudocysts in children who have suffered upper abdominal trauma, however minor.

The pharmacologic treatment of newborn diaphragmatic hernia--a 2-year evaluation.

From 1968 to 1976 inclusive, 69 neonates with diaphragmatic hernias had corrective surgery within 18 hr of birth and the survival rate was 41%. During the same time, all babies with similar hernias who were operated on later than 18 hr from the time of birth survived. Our present interest has been focused on the pulmonary artery and its hypertension with the subsequent development of right to left shunting through the patent ductus arteriosus. During 1977 and 1978, we attempted to enter 19 consecutive newborns 18 hr of age or less with symptomatic Bochdalek diaphragmatic hernias into a "Collins protocol" for treatment. This included four stages: newborn nursery initial resuscitation, operation, cardiac catheterization, and ICU monitoring and pharmacological therapy. There was a total of seven survivors (36%), however for a number of reasons only eight babies really had a complete entry into this protocol and of these eight, five survived. Although this study is far from complete, some initial information and concepts are forthcoming. It is now apparent to us that there are three distinct groups into which these very early newborns fall: minimal pulmonary hypoplasia, unilateral hypoplasia and bilateral hypoplasia. The first group probably does not need pharmacologic support, while in the last it probably does not help. Further interest in other more specific pulmonary pharmacologic agents is now being considered as well as some way of early recognition of which baby is going to fit into which group, so that only the ones that need this treatment will get it.

Nonsurgical management of appendiceal mass in late presenting children.

Thirty-seven late presenting children with appendiceal mass were treated between 1965 and 1975 with i.v. fluids, alimentation according to the state of gastrointestinal function, and no antibiotics. They ranged in age from 18 mo to 16 yr and all had had symptoms for at least 5 days (mean 8.7), an abnormal WBC (mean 19.9), and a fixed palpable mass without rebound tenderness. Children were discharged when clinical findings resolved. All returned for interval appendectomy. Eighty-one percent (31 children) had clinical improvement within 5-22 days (mean 10.9). Nineteen percent (7 children) had recurrence or worsening of symptoms and required abscess drainage within 2-10 days after observation began. No child in either group received antibiotics nor did any die. Only one recurrence of symptoms after discharge was recorded before interval appendectomy. Pathologic specimens revealed fibrosis in 46%, subacute inflammation in 35%, and acute inflammation in 19%. Nonoperative management of the appendiceal mass without antibiotics in children is safe as long as diligent observation is maintained. Interval appendectomy can be performed as late as 20 wk after symptom resolution or drainage, however, over 50% of the interval appendectomy specimens reveal acute and subacute inflammation.