The use of different induction and maintenance chemotherapy regimens for the treatment of advanced yolk sac tumors.

Four children with yolk sac tumor were treated with an aggressive combination chemotherapy program. Three children had presacral primary tumors, one having pulmonary metastases, and one had a testicular primary tumor with pulmonary metastases. Three children were treated when they had measurable disease, and one had no measurable disease. The chemotherapy program consisted of a 6-wk induction period with vincristine (VCR), cis-diamminedichloroplatinum (DDP), and bleomycin. Maintenance therapy consisted of VCR, actinomycin D, and cyclophosphamide (cytoxan) every 3-4 wk as tolerated. Treatment was discontinued after 12 mo of complete remission. All three patients with evaluable disease had a partial response (PR) to induction therapy. Two underwent surgical exploration following induction therapy, one a laparotomy and the other a thoracotomy, and were found to have only scar tissue at the sites of presumed residual disease. The third child with measurable disease progressed to a clinical complete response (CR) during maintenance therapy. Two patients have had no evidence of disease (NED) for 42+ and 41+ mo since starting therapy (28+ and 27+ mo since completing treatment). Two patients are NED 11+ and 7+ mo since starting therapy and remain on treatment. We have encountered no significant renal or pulmonary toxicity, and there have been only two hospitalizations during maintenance therapy for fever and neutropenia. These preliminary results employing different induction and maintenance chemotherapy programs and planned second-look surgical intervention appear encouraging.

Treatment of defects of the anterior abdominal wall in newborns.

Primary closure of an omphalocele or gastroschisis may cause respiratory compromise in the neonate. Some authors recommend primary closure of the defect with prolonged respiratory support because of dissatisfaction with staged visceral reduction and use of a Silastic pouch. Our experience with use of a Silastic pouch from 1975 to 1982 was reviewed. Twenty-three newborns with major defects of the abdominal wall (14 omphaloceles and 9 gastroschisis anomalies) were surgically treated, and only one death occurred. The mean birth weight of the infants was 2,927 g; nine of them were premature. Seven infants had major associated anomalies. The goal of the surgical procedure was closure of the abdominal wall without compromise of the cardiorespiratory status. During the operation, muscle relaxants were avoided and the infants breathed spontaneously. If progressive visceral reduction caused tachypnea (rate of more than 70/min) or hemodynamic instability, a Silastic pouch was constructed. Ten patients were treated with primary fascial closure, and 13 were treated with a Silastic prosthesis. The neonates with the prostheses required three to eight reductions, and the prostheses were in place for 4 to 22 days. No patient had wound dehiscence, wound infection, or an intestinal fistula. The one death occurred in an infant with trisomy 18 syndrome and multiple anomalies. Thus, the Silastic pouch was effective when the defect could not be closed primarily without respiratory compromise.

Limited thoracotomy in the pediatric patient.

Thirty-one children underwent 33 limited thoracotomies between 1973 and 1979. Adequate tissue for diagnosis was obtained in each case, and subsequent therapy was influenced in 91%. The preoperative diagnosis was confirmed in 61% and corrected in 36%. One death may have been hastened by the procedure, but all others were related to the underlying disease process. There were very few complications, the most common being pneumothorax. The routine use of a chest tube postoperatively seems to reduce the frequency of pneumothoraces. The average duration of the operation was 50 minutes. We believe that limited thoracotomy is a safe and rapid method of obtaining lung tissue and almost always ensures adequate tissue for diagnosis.

Relative merits of partial splenectomy, splenic reimplantation, and immunization in preventing postsplenectomy infection.

Partial splenectomy, splenic autotransplantation, and immunization with pneumococcal vaccine have been reported to protect patients against overwhelming postsplenectomy infection, and this study was undertaken to evaluate these therapeutic alternatives. For this purpose 136 rats were divided into experimental groups: 34 controls, 34 splenectomy, 34 partial splenectomy, and 34 splenic autotransplantation animals. Five weeks after operation, two-thirds of the animals were immunized with killed pneumococci. The effects of operation and immunization were studied by challenging the animals intravenously with pneumococci. Pneumococcal antibody titers were determined, and phagocytic uptake of pneumococci by the spleen and liver was measured. Immunization impressively increased the survival rate in all groups. At low-challenge doses autotransplantation prolonged survival. At higher-challenge doses only partial splenectomy increased survival. Partial splenectomy and control animals had higher antibody titers than did splenectomy and autotransplantation rats. Animals with the highest antibody titers had the greatest splenic and hepatic phagocytic uptake of pneumococci. Partial splenectomy was more efficient in removing pneumococci than was autotransplantation. Thus immunization is one of the most important factors contributing to survival after splenectomy. Partial splenectomy is preferable to splenic autotransplantation because it is associated with higher antibody titers after immunization, better pneumococcal splenic uptake, and improved survival rates.

Increased hepatic synthesis of cholesterol following jejunoileal bypass.

Fatty infiltration of liver and formation of cholesterol stones are significant problems following jejunoileal bypass for morbid obesity. This report evaluates hepatic lipid metabolism and fat absorption in genetically obese, bypassed, and lean Zucker rats. Ninety percent jejunoileal bypass was performed in 12 (500 grams) obese rats (BP). Similar numbers of unoperated "fat rats" (FR) and lean litter mates (LR) were controls. Food consumption, weight gain or loss, and fecal fat were evaluated. At 4 weeks serum triglycerides, hepatic cholesterol, total lipids, triglycerides, and hepatic synthesis of fatty acids and cholesterol were measured in vivo. Food intake was excessive in FR's (23.8 +/- 0.7 gm/day), decreased in BP (18.3 +/- 2.3 gm/day), and lowest in LRss ( less than 0.05) and excessive fecal fat excretion (p less than 0.05). Serum triglycerides were elevated in FR's (284 +/- 32 mg/dl), reduced in BP rats (148 +/- 20 mg/dl) (p less than 0.05), and low in LR's (86 +/- 16 mg/dl). Total hepatic lipids, triglycerides, and hepatic synthesis of fatty acids were elevated in FR's (p less than 0.05) and were unchanged by bypass. Hepatic cholesterol was similar in all groups. Hepatic synthesis of cholesterol, however, was increased significantly in bypassed rats (p less than 0.05), (BP--102 +/- 22 micronnmole/"C2"/minute/gm, FR--39 +/- 6.0, LR--30 +/- 4.0). Jejunolileal bypass in FR's results in weight loss, decreased food intake, increased fecal fat, decreased serum triglycerides, and increased hepatic synthesis of cholesterol. Bypass had little effect on reducing elevated hepatic lipids, triglycerides, or fatty acid synthesis in FR's. These data suggest that following bypass increased hepatic cholesterol synthesis (as a precursor for bile acids) is related to interruption of the enterohepatic circulation and bile salt pool depletion. This implies that excess synthesis of hepatic cholesterol results in supersaturation of bile which is choletithocenic and may explein in part the increased incidence of gall stones observed following jejunoileal bypass.

Adverse effects of jejunoileal bypass on growth and development.

Ninety percent jejunoileal bypass was performed in 20 growing (100 gram) male Sprague-Dawley (SD) and 15 male, genetically obese, growing (125 gram) Zucker "fat rats" (FR). Twenty SD and 15 FR unoperated rats of similar age and weight served as controls. Animals were evaluated for weight gain or loss, complications, and survival. At death (4 months), caliper measurements of long bones, vertebral column, pelvis, and skull were obtained, and brain, liver, spleen, and kidneys were excised and weighed. Liver and gonadal histology were obtained. The "fat fat" was more fragile, with a 20 percent anastomotic leak rate and a 33 percent mortality rate. The mortality rate was 5 percent (SD) and zero in controls. Bypassed animals showed growth retardation with weight of SD rats 31 percent (p less than 0.05) and FR's 19 percent of controls (p less than 0.05). Organ weights (liver, spleen, kidneys) were similar, except for a smaller brain in bypassed rats [SD 1.06 +/- 0.08 to 1.83 +/- 0.08 Gm. control (p less than 0.05), FR 1.2 +/- 0.12 to 1.68 +/- 0.09 control (p less than 0.025)]. Skeletal development was retarded significantly in bypassed rats [vertebral column, 125.9 +/- 3.5 to 138.3 +/- 3.9 mm. in controls (p less than .025); ilium, 39.4 +/- 1.1 to 46.2 +/- 1.5 mm. in controls (p less than 0.05); skull circumference, 20.2 +/- 0.03 to 22.5 +/- 0.05 mm. in controls (p less than 0.025)]. No increase in fatty infiltration of liver was observed. Spermatogenesis was diminished 30 percent (p less than 0.05) in bypassed (SD) animals. The data document significant morbidity and mortality rates, growth retardation, and diminished spermatogenesis in bypassed "adolescent" rats. These results imply that jejunoileal bypass may affect intellectual, skeletal, and reproductive development adversely and question the advisability of these procedures in growing subjects.

Gastrointestinal tube stent plication in infants and children.

Twenty cases of intestinal obstruction in infants and children were managed by gastrointestinal tube stent plication. The mean age was 2.6 years, and ten patients were infants. Previous (often multiple) abdominal operations were performed in 18 patients with a variety of anomalies. Tube plication was used at initial operation in two neonates with malrotation. Following lysis of adhesions, a No. 12 or No. 16 tube (usually a Baker tube) was inserted by gastrostomy and advanced distally into the colon. The tube was kept in place for ten days, with caloric needs supplied by parenteral alimentation. Barium tubogram showed distal patency, and the tube was removed. Eighteen patients survived (90%), and obstruction was relieved in each instance. These observations suggest that gastrointestinal tube stent plication is a useful adjunctive procedure in carefully selected cases or recurrent adhesive intestinal obstruction in infants and children.

Intramural hematoma of the duodenum.

Intramural duodenal hematoma in children is one of the least common injuries encountered. Because of the rarity of this problem, there has been little conformity of opinion as to the relative merits of operative vs nonoperative management. We reviewed 182 cases of this condition, of which 168 were taken from the English literature and 14 from our hospital. Pancreatitis was the most common associated intra-abdominal lesion (21%), while central nervous system, skeletal, and thoracic injuries (5%) accounted for the major extra-abdominal injuries. Hemophilia, von Willebrand's disease, and idiopathic thrombocytopenic purpura occurred in 7 cases and played a major role in the prognosis. Of these cases, 121 patients were treated surgically and 61 conservatively. The average hospitalization was 14 days for the surgical group and 11 days for the conservative group. There were 18 complications in the surgical group. It appears that most patients with intramural duodenal hematoma would respond well to conservative management. Surgery should be reserved for those cases that remain obstructed over seven to ten days or have evidence of perforation.

Presentation of congenital diaphragmatic hernia past the neonatal period.

Congenital diaphragmatic hernias (CDHs) presenting beyond the neonatal period are a rare and unusual problem; they occurred in 11 of 83 children at our institution. Two discrete clinical groups were apparent: (1) younger children, with mainly respiratory symptoms; and (2) older children with gastrointestinal (GI) complaints. Chest roentgenograms suggested CDHs, but GI contrast studies were necessary for confirmation in eight patients. The diagnosis was made preoperatively in ten of 11 children. At operation, no peritoneal sacs were found, the hernial contents were viable in all patients, and malrotation was present in six of 11 patients. None had evidence of pulmonary hypoplasia. Congenital diaphragmatic hernias do present beyond the neonatal age group in a significant number of cases (13% in our series), and a diagnosis of CDH should be considered in any child with persistent GI or respiratory problems and abnormal chest x-ray film findings. The mortality rate in these patients is small, but morbidity may be significant.

Computed tomography and ultrasonography in the diagnosis of appendicitis: when are they indicated?

HYPOTHESIS: Relative merits and indications exist for ultrasonography (US) and computed tomography (CT) in the diagnosis of appendicitis. DESIGN: Prospective study. SETTING: General community and tertiary care hospital. METHODS: Ninety-nine patients (50 males and 49 females) were studied. Following consent, the initial disposition was recorded, designating the patient for operation, observation, or discharge from the hospital. Each patient was studied by CT and US. Studies were independently evaluated by 2 radiologists, and the results were designated as positive, negative, or equivocal. The surgeon reevaluated patients before and after learning the results of US and CT, recording whether the CT scan, US, or reexamination influenced the final disposition. RESULTS: Fifty patients had appendicitis; 6 appendixes were perforated. The initial clinical impression called for 44 operations, 49 observations, and 6 discharges. Thirty-four patients had their treatment plan changed from the initial disposition. Ultrasonography did not affect the initial impression. In contrast, 18 patients were rediagnosed solely on CT scan findings. Seven patients were rediagnosed by reexamination. Of 44 patients initially designated for operation, the CT scan and reexamination spared 6 females from surgery; the negative appendectomy rate potentially decreased from 50% to 17% (P =.03). The CT scan, US, or reexamination failed to spare 2 males from exploration with negative results. Of the 49 patients initially designated for observation, 23 were rediagnosed after reevaluation, 13 were discharged from the hospital, and 10 underwent expedient operation. One patient was spared from inappropriate discharge from the hospital. The reliability of the CT scan was good, with high sensitivities and specificities. Equivocal scan results lowered the diagnostic value. CONCLUSIONS: Selective use of a CT scan with a second examination can improve the diagnostic accuracy and management of suspected cases of appendicitis by (a) reducing the negative appendectomy rate in females, (b) moving patients from observation to earlier operation or discharge from the hospital, and (c) preventing inappropriate discharge of patients with appendicitis.

Cholecystokinin: a factor responsible for the enteral feedback control of pancreatic hypertrophyphy.

Chronic diversion of pancreatic and biliary secretions away from the proximal small intestine results in pancreatic hypertrophy in adult rats. Serum levels of cholecystokinin (CCK) were measured in age-matched control and surgically diverted rats at various times after operation by a radioimmunoassay method that was specific for the sulfated form of CCK. The concentration of CCK was markedly increased in bypassed rats as compared with controls. The increases in circulating CCK in bypassed rats was substantiated by a bioassay method that measured physiologically active CCK. The degree of pancreatic hypertrophy and the increase in CCK levels both progressed with time up to 23 days after surgery. Linear regression analysis showed an apparent direct correlation between pancreatic weights and serum CCK levels (r = 0.99). Feeding bypassed rats with diets containing various pancreatic and biliary supplements did not abolish the hyperplastic response of their pancreata. However, feeding with diets supplemented with bile partially suppressed the increase in serum CCK levels, while a diet containing Cotazyme and bile completely suppressed this increase. The discrepancy between serum CCK levels and the degree of pancreatic hypertrophy in the supplemented bypassed rats was further demonstrated by the lack of correlation using linear regression analysis (r = 0.33). The observed pancreatic hypertrophy in the absence of high serum levels of CCK in the bypassed rats fed bile and Cotazyme supplements suggests that serum hypertrophic factors other than CCK may also be involved in the enteral feedback regulation of pancreatic growth.

Splenic and hepatic trauma in children.

The concepts for proper management of splenic and hepatic injuries have been evolving over the last several years. The recognition that aggressive surgical therapy in some instances was responsible for the number of life-threatening complications led to a reappraisal of the principles of care for these traumatic lesions. The emerging consensus of opinion is that often nonoperative therapy or more "conservative" operations are preferable. The accumulated experience to date supports the view that this more selective therapeutic approach will result in lower morbidity and mortality for children sustaining splenic or hepatic injuries. Fortunately, the recent technologic improvements in the field of radiology have enabled the clinician to diagnose and serially evaluate these major intra-abdominal injuries with a high degree of confidence.

Pancreatic and gastrointestinal trauma in children.

Injuries to the pancreas and gastrointestinal tract following blunt abdominal trauma continue to be a significant cause of morbidity and mortality in the pediatric age group. Optimal treatment of these injuries is frequently hampered by considerable delays in diagnosis. Factors contributing to these delays include the location of much of the duodenum and the pancreas in the retroperitoneum resulting in an absence of initial symptoms and signs, the often trivial nature of some of the responsible blunt traumatic accidents, inappropriate child-parent or child-physician communication, failure to achieve a meaningful physical examination in uncooperative or unconscious patients, and false negative paracentesis. Eighty per cent of these injuries occurred in boys. Eleven of 16 patients with pancreatic trauma had pseudocysts. A persistently elevated serum amylase level was invariably noted and epigastric mass was palpable in eight patients. Significant delays in diagnosis were prevalent and pseudocysts was misdiagnosed as appendicitis in three cases. Internal drainage by cystgastrostomy or cystjejunostomy was effective operative treatment. In instances of acute pancreatic injuries, sump drains, gastrostomy, cholecystostomy, and total parenteral hyperalimentation were useful therapeutic adjuncts. There was one death for a 6.2 per cent mortality rate. Forty patients had gastrointestinal injuries involving the duodenum in 17, jejunum in 14, ileum in seven, and stomach in two. Perforations occured in 65 per cent of cases, obstructing hematomas in 30 per cent, and mesenteric avulsions in 5 per cent. Associated injuries were observed in 15 patients (37.5 per cent). Pain and tenderness were the only consistent findings. Upper gastrointestinal contrast studies were diagnostic of duodenal hematomas. Eighty per cent of perforations were managed by simple closures and 20 per cent by resection and anastomosis. Obstructing hematomas unassociated with other injuries may be expected to resolve without requiring operation in 50 per cent of patients managed conservatively. Complications occurred in 35 per cent of patients and the mortality rate was 12.5 per cent (five deaths).

Maternal and postnatal hypermagnesemia and the meconium plug syndrome.

Thirty dated pregnant Srague-Dawley rats received IM MgSO4 (750 mg/kg/ X 5 days) until birth. Fifteen untreated pregnant Sprague-Dawley rats of similar gestation served as controls. A total of 453 rats were born. Ninety neonates (two from each of 45 liters) were randomly removed before suckling, sacrificed, and the water content of the meconium and serum magnesium determined. The remaining 363 bewborn rats were observed for delayed passage of meconium or abdominal distention. Hypermagnesemic (6.3 +/- 0.5 mg/100 ml) neonates had neither abdominal distention nor delayed passage of meconium. The water content of meconium in hypermagnesemic rats (84.7 +/- 4.2% and in untreated controls (85.5 +/- 3.8%) were statistically similar. Dated pregnant mongrel dogs were given magnesium sulfate by continuous intravenous infusion and by bolus intravenous injection. The water content of meconium, transit time, and basic electrical rhythm (BER) of treated neonates were similar to untreated neonatal controls. The water content of meconium, transit time, and BER of neonatal dogs made hypermagnesemic (12.0 +/- 1.2 mg/100 ml) in the postnatal period were similar tp untreated neonatal controls. In adult and newborn pupies, receiving a continuous intravenous magnesium sulfate infusion, deep tendon reflexes ceased at serum magnesium levels of 9.0-10.0 mg/100 ml, spontaneous respiration at 14.0-15.0 mg/100 ml, and BER was suppressed (transiently) at 20.0-25.0 mg/10 ml. These data suggest that high (sublethal) doses of MgSO4 in pregnant and newborn animals have little effect on BER, meconium transit time or water content of the neonates. No correlation between MgSO4 treatment and the meconium plug syndrome was observed in the experiments.

A long-term follow-up on a duplication of the entire small intestine treated by gastroduplication.

Duplication of the entire small intestine resulting in gastrointestinal hemorrhage was managed by excision of the ulcerogenic lesion, ileo-ileostomy, and diversion of the gastric-lined intestinal duplication into the stomach. A 25 yr followup study reveals no evidence of recurrent bleeding or malabsorption secondary to bind-loop syndrome. This operative procedure is worthy of consideration in patients with this congenital anomaly.

Pancreaticocolonic fistula: a complication of pancreatic pseudocysts in childhood.

Two patients had an unusual complication of pancreatitis: pancreaticocolonic fistula, frequently associated with life-threatening gastrointestinal hemorrhage and sepsis. To avoid these complications, early diagnosis is important, but it may be difficult. Treatment consists of external drainage of the pancreatic pseudocyst or abscess and colonic diversion.

Use of fresh amnion as a burn dressing.

Thirty-seven children with second and third degree burns dressed with amnion were compared to seventy-three children treated with Furacin (Eaton Labs, Norwich, N.Y.) dressing. Amnion was found to be as easy to use as Furacin. Fewer split thickness skin grafts were needed in amnion treated children and these patients required fewer days of hospitalization. Bacterial culture data suggests that amnion is as good as and possibly superior to nitrofurazone in decreasing the number of organisms on the burn wound. No adverse reactions to amnion were noted. The use of amnion is supported by this preliminary study and is deserving of further investigation and clinical use.

"Acquired" lobar emphysema: a complication of respiratory distress in premature infants.

Ten premature infants with respiratory distress developed a type of pulmonary lobar emphysema that is clinically and histologically distinct from interstitial or congenital lobar emphysema. In eight patients emphysema was noted in the right lower lobe, while in two the left upper lobe was affected. Five infants exhibited nonresolution of the emphysema and an inability to be weaned from ventilator support. Lung scans in these five infants showed absent or markedly decreased perfusion of the involved lobe. Lobectomy was necessary. Postoperatively, their respiratory status improved and they were successfully weaned from the ventilator. Five premature infants with identical radiographic emphysematous changes had normal lung scans. These infants did not require lobectomy and were also successfully weaned from the ventilator. Radiographic changes of lobar emphysema in these five infants completely resolved. Pathologic changes in the excised lobes were characteristic of bronchopulmonary dysplasia and obstructive intraalveolar emphysema. The long-term effects of positive pressure ventilation, oxygen, and suctioning techniques directed toward the right lower lobe may play an important role in the etiology of "acquired" lobar emphysema.

Combined preoperative and postoperative immunotherapy for murine C1300 neuroblastoma.

Preoperative treatment of murine C1300-neuroblastoma (C1300) with triple immunotherapy using low-dose cyclophosphamide (CY), retinyl palmitate (RP), and interleukin-2 (IL2), followed by tumor resection leads to significant initial tumor control and prolonged survival. However, because long-term tumor recurrence is 67%, the efficacy of continued postoperative immunotherapy is now evaluated. Thirty-two A/J mice with 1 cm subcutaneous C1300 tumors were treated for 13 days with CY-100 mg/kg, intraperitoneally (IP), on day 2 of treatment then 25 mg/kg on day 9, RP-2500 IU IP 2 x/week, and IL2 1.6 x 10(5) U IP BID on days 4 to 9 and 11 to 13. On day 14, mice were divided into five treatment groups: (1) OP (operated-tumor resection, n = 6); (2) OP+CY (resection and postoperative CY, n = 7); (3) OP+CY+RP (resection and postoperative CY+RP, n = 7); (4) OP+CY+RP+IL2 (resection and postoperative CY+RP+IL2, n = 7); and (5) CY+RP+IL2 (continued CY+RP+IL2 with no resection, n = 5). Survival and postoperative tumor recurrence were followed for 60 days. The cure rates were group 1 33% (2/6), group 2 43% (3/7), group 3 29% (2/7), group 4 71% (5/7), and group 5 20% (1/5). After surgery, tumors that recurred did so in 8 to 22 days, with no statistical difference noted between groups. MHC class I antigenic expression of tumors resected on day 14 and recurrent tumors was determined with monoclonal antibodies and flow cytometry. In tumors resected on day 14, class I expression measured by mean fluorescence, was 374.8 +/- 27.40.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of the pediatric surgical matching program by the directors of pediatric surgical training programs.

In a previous survey of successful candidates (SC) and unsuccessful candidates (USC) to the pediatric surgery matching program (PSMP), significant discriminating factors associated with SC included previous participation in basic science research, number of publications, number of national presentations, and contact with and letters of recommendation from well-known pediatric surgeons. The purpose of this study was to determine the selection criteria used by directors of the pediatric surgery training programs (PSTP) in choosing residents for the PSMP. A two-part survey of the PSMP was completed by directors of the PSTP (n = 24) to identify the factors (n = 31) that most influence their selection process when choosing a resident, and to help clarify questions (n = 11) posed by the candidates during the first survey. In part I, each factor was scored on a modified Likert Scale, from most (1) to least (5) important in evaluating candidates for training positions, and were ranked according to the mean score. Based on our previous survey, but blinded to the PSTP director respondents, these same factors were divided into groups that, in our first survey, did and did not discriminate between SC and USC for the PSMP, and will be referred to as "discriminating factors" (DF, n = 7) and "non-discriminating factors" (NDF, n = 8), respectively. Also, a series of questions dealt with subjective factors of the candidates, not previously analyzed in our original survey, and will be referred to as "program directors' factors" (PDF, n = 16). The three groups (DF, NDF, PDF) were analyzed by the Kruskal-Wallis test and analysis of variance (ANOVA).(ABSTRACT TRUNCATED AT 250 WORDS)