Charles S. Turner

A risk-adapted, response-based approach using ABVE-PC for children and adolescents with intermediate- and high-risk Hodgkin lymphoma: the results of P9425

Current treatment strategies for Hodgkin lymphoma result in excellent survival but often confer significant long-term toxicity. We designed ABVE-PC (doxorubicin, bleomycin, vincristine, etoposide, prednisone, cyclophosphamide) to (1) enhance treatment efficacy by dose-dense drug delivery and (2) reduce risk of long-term sequelae by response-based reduction of cumulative chemotherapy. Efficient induction of early response by dose-dense drug delivery supported an early-response-adapted therapeutic paradigm. The 216 eligible patients were younger than 22 years with intermediate- or high-risk Hodgkin lymphoma. ABVE-PC was administered every 21 days. Rapid early responders (RERs) to 3 ABVE-PC cycles received 21 Gy radiation to involved regions; RER was documented in 63% of patients. Slow early responders received 2 additional ABVE-PC cycles before 21 Gy radiation. Five-year event-free-survival was 84%: 86% for the RER and 83% for the slow early responders (P = .85). Only 1% of patients had progressive disease. Five-year overall survival was 95%. With this regimen, cumulative doses of alkylators, anthracyclines, and epipodophyllotoxins are below thresholds usually associated with significant long-term toxicity. ABVE-PC is a dose-dense regimen that provides outstanding event-free survival/overall survival with short duration, early-response-adapted therapy.

Congenital cyst of the pancreas.

The case of a 4-month-old girl with a rare multilocular congenital pancreatic cyst is presented, along with radiological/pathological correlation and a review of the literature. Congenital cyst of the pancreas is a rare lesion most often seen in infant girls, although it may be demonstrated in utero. Conventional radiographic signs and clinical symptoms primarily reflect mass effects, whereas imaging modalities show the cystic nature of the mass. Although rare, this cyst should be considered in the differential diagnosis of fetal and pediatric cystic abdominal masses.

Intestinal Perforation in Very Low Birth Weight Infants: Growth and Neurodevelopment at 1 Year of Age

OBJECTIVE:To compare growth and neurodevelopment in surviving very low birth weight (VLBW) infants with an intestinal perforation (IP) caused by necrotizing enterocolitis (NEC) versus spontaneous intestinal perforation (SIP).STUDY DESIGN:Retrospective, observational cohort study. Infants born between January 1996 and December 1999 with birth weight <1500 g and a diagnosis of intestinal perforation were identified and data extracted from NICU, surgical and hospital databases.RESULTS:IP was identified in 62 of 1357 VLBW infants (5%); 39 infants (63%) had surgical NEC and 23 (37%) had SIP. Among survivors, 21/28 with surgical NEC (75%) and 13/18 with SIP (72%) returned for follow-up. At 1-year adjusted age, there were no differences in growth parameters but the Mental Developmental Index (MDI) and Psychomotor Developmental Index (PDI) were lower in survivors with NEC versus SIP (mean difference in MDI=15; 95% confidence limits=3, 28; p=0.02; mean difference in PDI=14; 95% confidence limits=0.4, 28; p=0.04).CONCLUSIONS:Intestinal perforation caused by NEC, as compared to SIP, is associated with worse neurodevelopmental outcome at 1 year.

Dexamethasone treatment during ventilator dependency: possible life threatening gastrointestinal complications.

Corticosteroids in high doses have been used effectively to decrease the duration of ventilator dependency in very low birthweight infants at risk for chronic lung disease. Randomised prospective studies have shown benefit, with only minimal complications being reported. However, review of our experience over 2.5 years with high dose steroids in 80 premature neonates yielded three major complications: one case each of perforated duodenal ulcer, perforated gastric ulcer, and upper gastrointestinal haemorrhage. Two of the three patients died. Thus the use of steroids in neonates may not be without risk, and significant complications can occur. When high dose corticosteroids are to be used in very low birthweight neonates, H2 receptor antagonist treatment and gastric pH monitoring are recommended. The physician must remain alert to the possibilities of upper gastrointestinal bleeding and ulcer perforation in these patients.

Ollier disease (enchondromatosis) associated with ovarian juvenile granulosa cell tumor and precocious pseudopuberty

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Serum visceral protein levels reflect protein-calorie repletion in neonates recovering from major surgery.

Protein catabolism resulting from acute metabolic stress causes significant postoperative decreases in visceral proteins, including albumin (Alb) and prealbumin (PA). Although clinical trials have suggested an advantage of PA over Alb in monitoring the visceral protein response to nutritional supplementation following surgery, the capability of the neonate to generate such a response has yet to be evaluated. Therefore, this study was undertaken to determine if PA is superior to Alb in assessing postoperative repletion of the visceral protein pool in neonates. Serum Alb and PA levels were measured and energy balance (EB) and protein intake (PI) were recorded in 10 neonates less than 48 hours after major surgery and again following 4 consecutive days of positive EB. Resting energy expenditure (REE) was measured using indirect calorimetric methodology. Mean PI (g/kg/d) was lower (0.78 +/- 0.78) and mean EB (kcal/kg/d) was negative (-2.92 +/- 10.05) less than 48 hours postoperatively compared with mean PI (2.52 +/- 0.57; P = .0006) after 4 consecutive days of positive EB (34.84 +/- 16.5; P = .0004). Mean percent change (mean% delta) from negative EB to positive EB was significantly greater for PA (100%; P = .0002) as compared with Alb (18.5%). These data appear to support the conclusion that serial serum PA levels are superior to Alb to monitor the visceral protein response to nutritional supplementation in neonates following surgery.

Vagal hypertonia and anesthesia in Angelman syndrome.

SIR—We write to raise awareness of possible vagal hypertonia when caring for patients with Angelman syndrome (AS) in the perioperative period. Although little information is available, AS and anesthetic management has been described (1,2); however, there is little attention to possible cardiac rhythm disturbance from vagal hypertonia in the care of these patients during the perioperative period. Additionally, there is no mention of potential cardiac rhythm disturbance in general descriptions of AS, as the vagal hypertonia is only considered from a neurologic standpoint and not from its cardiovascular implications (1,3,4). We report a case of asystole during laparoscopy in a child with AS, review the previous case reported with respect to cardiac rhythm disturbance and present the literature pertaining to vagal hypertonia and cardiac rhythms in AS. Recently, the management of AS was reviewed with a good discussion of the syndrome and the implications of the genetic disorder (2). This report presented the case of a 12-year-old boy with AS who underwent general anesthesia for dental conservation. Notably, the patient unexpectedly developed severe bradycardia – with a significantly delayed reaction to atropine not proportional to the dose. Although the cardiac rhythm returned to normal following this incident, we believe this may be related to the predominance of vagal tone in AS which any provider caring for these patients should consider (5,6). Recently, we cared for a 9-year-old, 33-kg female for exploratory laparoscopy and exam under anesthesia for a 3.5 cm · 3 cm left ovarian mass. Medical history was notable for AS and seasonal allergies. Her medications included oral cetirizine 10 mg daily, oral montelukast 5 mg daily and a Lactobacillus and Bifidobacterium probiotic elixir daily. No family history of anesthetic complications was reported. The patient was premedicated with oral midazolam 0.5 mgÆkg. Following onset of adequate hypnosis, she was transported to the operating suite where standard monitors were placed. An inhalational induction was performed with 70% nitrous oxide and sevoflurane. A 22 g intravenous (IV) catheter was placed and rocuronium 20 mg IV was administered. An endotracheal tube was atraumatically passed via direct laryngoscopy and confirmed by the presence of bilateral breath sounds and endtidal CO2. Prior to incision, cefoxitin 1 gm IV was administered prophylactically. Approximately 20 min after antibiotic administration, incision was made and the patient remained hemodynamically stable. Pneumoperitoneum was established gradually over 45 s via needle peritoneal insufflation. The patient was noted to become bradycardic at which time 0.4 mg of IV atropine was given with little response. The surgical procedure was halted and the pneumoperitoneum released. However, the bradycardia deteriorated into asystole. Chest compressions were initiated and IV epinephrine 10 lgÆkg was administered. Following approximately 90 s of cardiopulmonary resuscitation, sinus tachycardia was noted on the electrocardiogram with a thready, palpable pulse. The presence of bilateral breath sounds was confirmed. To maintain blood pressure continued small doses of epinephrine were required and the patient was empirically treated for anaphylaxis with diphenhydramine and methylprednisolone. An epinephrine infusion was required for continued and intermittent hypotension. A transesophageal echocardiographic examination was performed which demonstrated no structural abnormalities or significant valvular disease of the heart. No air in the heart or in the pulmonary artery was visualized. An arterial line was placed in the left radial artery for hemodynamic monitoring. The blood pressure was maintained with an epinephrine infusion. After discussion with the surgical team, it was felt that the patient was stable enough to proceed with the surgical procedure, which the patient tolerated without further event. Epinephrine infusion was gradually reduced throughout the procedure, but still required. The patient was subsequently transferred to the pediatric intensive care unit (ICU) and required continued pressor and respiratory support for the following 72 h. A tryptase level was normal. During her time in the ICU, intermittent episodes of rhythm slowing were noted, but were not significant. There were also large swings in blood pressure as she awoke from sedation with drops in blood pressure. The patient was extubated on postoperative day 4 and placed on the floor on telemetry. No episodes of asystole were noted, but once again episodic slowing of the cardiac rhythm was noted by telemetry, but these were minimal and no bradycardia (heart rate <60) was noted. The patient was discharged home on postoperative day 8 without apparent neurologic sequelae. Skin allergy testing was negative for anesthesia-related drugs, antibiotics and latex. The occurrence of sudden intraoperative hemodynamic collapse may be precipitated by anaphylaxis, anaphylactoid reactions and given the temporal relationship with abdominal insufflation, the possibility of venous gas embolism (VAE), tension pneumothorax and severe vagal responses should also be entertained. Tension pneumothorax was quickly determined to be less likely, as breath sounds were present and equal bilaterally with normal airway pressures. Similarly, VAE too was unlikely as 348 CORRESPONDENCE

Early Enteral Fat Supplementation with Microlipid® and Fish Oil in the Treatment of Two Premature Infants with Short Bowel

The infusion of Intralipid® is a main risk factor for parenteral nutrition-associated cholestasis in infants with short bowel syndrome. Early provision of enteral fat to reduce the use of Intralipid while providing adequate fat for the growth of infants with short bowel has not been reported. We present 2 cases of premature infants with short bowel who received early supplementation of enteral Microlipid® and fish oil. This approach allowed us to discontinue Intralipid shortly after initiating feedings. The infants tolerated Microlipid/fish oil well without adverse reactions, had appropriate weight gain and ostomy output. They underwent bowel reanastomosis 3 weeks after enteral feeding began, and were discharged on full oral feedings. In case 1, the infant did not develop parenteral nutrition-associated cholestasis; in case 2, cholestasis had developed before initiating feeds, but was not aggravated by enteral fat and was improving prior to discharge.

A Novel Nutritional Approach to Prevent Parenteral Nutrition–Associated Cholestasis in Two Premature Infants with Short Bowel Syndrome

Infusion of soybean oil-based Intralipid is a major risk factor for parenteral nutrition (PN)–associated cholestasis that often occurs in infants treated with prolonged PN for short bowel syndrome. Parenteral fish oil–based lipid emulsion (Omegaven) has been reported to treat this condition, but it is not readily available in the United States and still requires a central venous catheter for administration. Enteral administration of Microlipid has been shown to decrease ostomy output and facilitate weight gain in infants with enterostomies. We describe 2 premature infants with short bowel syndrome who received early supplementation with enteral Microlipid and fish oil after bowel resection, and became independent of PN without cholestasis.

Congenital hypertrophic pyloric stenosis.

Pyloric stenosis (PS) has been reported in multiple births. We report the presentation of PS in identical twins, whose symptoms led to simultaneous referral for surgical care. The theories of inheritance of PS are reviewed.