Robert K. Minkes

Developmental adaptation of the mouse cardiovascular system to elastin haploinsufficiency

Supravalvular aortic stenosis is an autosomal-dominant disease of elastin (Eln) insufficiency caused by loss-of-function mutations or gene deletion. Recently, we have modeled this disease in mice (Eln+/-) and found that Eln haploinsufficiency results in unexpected changes in cardiovascular hemodynamics and arterial wall structure. Eln+/- animals were found to be stably hypertensive from birth, with a mean arterial pressure 25-30 mmHg higher than their wild-type counterparts. The animals have only moderate cardiac hypertrophy and live a normal life span with no overt signs of degenerative vascular disease. Examination of arterial mechanical properties showed that the inner diameters of Eln+/- arteries were generally smaller than wild-type arteries at any given intravascular pressure. Because the Eln+/- mouse is hypertensive, however, the effective arterial working diameter is comparable to that of the normotensive wild-type animal. Physiological studies indicate a role for the renin-angiotensin system in maintaining the hypertensive state. The association of hypertension with elastin haploinsufficiency in humans and mice strongly suggests that elastin and other proteins of the elastic fiber should be considered as causal genes for essential hypertension.

Transanal one-stage soave procedure for infants with Hirschsprung's disease☆

PURPOSE Many centers perform a one-stage pull-through procedure for Hirschsprungs disease (HD) diagnosed in infancy. The authors have developed a one-stage pullthrough procedure using a transanal approach that eliminates the need for intraabdominal dissection. METHODS Nine children aged 3 weeks to 18 months with biopsy-proven HD underwent a transanal pull-through procedure over a 13-month period. A rectal mucosectomy was performed starting 0.5 cm proximal to the dentate line, and extending proximally to the level of the intraperitoneal rectum. In the first eight children, intraperitoneal position was confirmed with a laparoscope placed through a 3- to 5-mm port in the base of the umbilicus. The muscular sleeve was divided circumferentially to allow full-thickness mobilization of the rectosigmoid junction. Manual transanal traction permitted direct visualization and division of mesenteric vessels with transanal mobilization above the transition zone. Ganglion cells were confirmed by frozen section, and the bowel was transected. The rectal muscular cuff was divided longitudinally, and the anastomosis was completed. The laparoscope confirmed orientation and adequate hemostasis. In a ninth patient, the identical procedure was performed, but with the laparoscope used only for confirmation at the end of the procedure. RESULTS Operative time, including frozen sections, averaged 194 minutes (range, 169 to 250 minutes), and the average length of bowel resected was 12 cm (range, 7.5 to 22 cm). Four of the nine patients were discharged on postoperative day (POD) 1, four on POD 2, and one patient with Downs syndrome was discharged on POD 6. Median follow-up was 6 months (range, 3 to 14 months). One death occurred 2.5 months postoperatively secondary to sudden infant death syndrome. Complications included postoperative apnea spells (n = 1), mild enterocolitis (n = 2), constipation (n = 1), anastomotic stricture(n = 1), and muscularcuff narrowing (n = 1); each responded to nonoperative management. Stool output has ranged from four to eight per day. CONCLUSION A one-stage pull-through for HD can be performed successfully using a transanal approach without intraperitoneal dissection. This procedure is associated with excellent clinical results and permits early postoperative feeding, early hospital discharge, and no visible scars.

One-stage transanal Soave pullthrough for Hirschsprung disease: a multicenter experience with 141 children.

Background: The surgical management of Hirschsprungs disease (HD) has evolved from the original 3-stage approach to the recent introduction of minimal-access single-stage techniques. We reviewed the early results of the transanal Soave pullthrough from 6 of the original centers to use it. Methods: The clinical course of all children with HD undergoing a 1-stage transanal Soave pullthrough between 1995 and 2002 were reviewed. Children with a preliminary stoma or total colonic disease were excluded. Results: There were 141 patients. Mean time between diagnosis and surgery was 32 days, and mean age at surgery was 146 days. Sixty-six (47%) underwent surgery in the first month of life. Forty-seven (33%) had the pathologic transition zone documented laparoscopically or through a small umbilical incision before beginning the anal dissection. Mean blood loss was 16 mL, and no patients required transfusion. Mean time to full feeding was 36 hours, mean postoperative hospital stay was 3.4 days, and 87 patients (62%) required only acetaminophen for pain. Early postoperative complications included perianal excoriation (11%), enterocolitis (6%), and stricture (4%). One patient died of congenital cardiac disease. Mean follow-up was 20 months; 81% had normal bowel function for age, 18% had minor problems, and 1% had major problems. Two patients required a second operation (twisted pullthrough, and residual aganglionosis). One patient developed postoperative adhesive bowel obstruction. Conclusion: To date, this report represents the largest series of patients undergoing the 1-stage transanal Soave pullthrough. This approach is safe, permits early feeding, causes minimal pain, facilitates early discharge, and presents a low rate of complications.

Blunt duodenal injuries in children

BACKGROUND Duodenal injury secondary to blunt trauma continues to pose a diagnostic challenge. The purpose of this study is to evaluate the cause, radiologic findings, and management of duodenal injuries from a Level I pediatric trauma center. METHODS A retrospective review of our trauma registry from 1990 to 2000 identified 24 children with blunt duodenal injuries. Clinical and radiographic findings and management strategies were assessed and compared in children with duodenal hematomas and perforations. RESULTS The majority of injuries were secondary to motor vehicle collisions. Pancreatic (42%) injuries were most commonly associated with duodenal trauma. With the exception of hematocrit level, initial clinical and laboratory findings were similar between groups. Of the 19 (79%) with duodenal hematomas, computed tomographic (CT) scan alone identified 15 and the remaining 4 were confirmed by duodenography. Incision and drainage of a hematoma was performed in two children. Duodenal perforation was identified in five (21%) children. Extraluminal air by CT scan was present in three of five children with perforation; however, none had extravasation of contrast. Four (80%) children with perforations underwent primary repair and one (20%) required segmental resection. CONCLUSION CT scanning remains a valuable tool in the diagnosis of blunt duodenal injuries in children. Although extravasation of oral contrast was not beneficial, the presence of extraluminal air was highly suggestive of perforation. The vast majority of hematomas were successfully managed nonoperatively, and duodenorrhaphy was safe and effective therapy for perforations.

Desmoplastic Nested Spindle Cell Tumor of Liver: Report of Four Cases of a Proposed New Entity

Abstract:We describe a distinctive tumor of the liver in four children composed of nested spindled and epithelioid cells with extensive desmoplasia that we have termed “desmoplastic nested spindle cell tumor of the liver.” All four patients were previously healthy. One patient had a presumptive diagnosis of hepatic hemangioma 11 years prior to presentation. Grossly, the tumors were well circumscribed, lobular white masses, ranging from 2.8 to 15 cm in diameter. These tumors were characterized by the presence of cohesive nests of plump, bland spindle cells arranged in short fascicles with an accompanying desmoplastic stroma. Epithelioid areas ranging from palisading epithelioid cells at the periphery of some nests to pseudoglandular and polygonal cells with intercellular bridges were invariably present. Mitotic activity was low. Calcification and ossification were present. Non-neoplastic bile ducts and hepatic elements were seen both within and surrounding the tumor cell nests. Each tumor displayed cytoplasmic reactivity for vimentin, pan-cytokeratin, CD57, and nuclear staining for WT1. Neuroendocrine markers were negative. Ultrastructurally, the tumor cells showed focally well-developed cell junctions, basal lamina, and few cytoplasmic organelles. All tumors were confined to the liver and were resected without complication. Two patients received postoperative adjuvant therapy for presumed hepatoblastoma. The patients are doing well without recurrence at 7.5 years, 7 years, 5 years, and 8 months post-surgery. The morphologic appearance and immunohistochemical profile of these lesions are unique in our experience and represent a new category of pediatric liver tumor.

Intestinal obstruction after lung transplantation in children with cystic fibrosis.

BACKGROUND/PURPOSE Distal intestinal obstruction syndrome (DIOS) occurs in 15% of patients with cystic fibrosis (CF). The authors reviewed their experience to determine the incidence, risk factors, and natural history of adhesive intestinal obstruction and DIOS after lung transplantation. METHODS Eighty-three bilateral transplants were performed in 70 CF patients between January 1990 and September 1998. All were on pancreatic enzymes preoperatively, and none had preoperative bowel preparation. Fifty-six patients (80%) had prior gastrostomy (n = 54) or jejunostomy (n = 2). Eighteen patients (25.7%) had a previous laparotomy for meconium ileus (n = 8), fundoplication (n = 4), liver transplant (n = 1), jejunal atresia (n = 1), Janeway gastrostomy takedown (n = 1), pyloromyotomy (n = 1), free air (n = 1), or appendectomy (n = 1). RESULTS After lung transplantation, 7 patients (10%) required laparotomy for bowel obstruction (6 during the same hospitalization, and 1 during a subsequent hospitalization). The causes of obstruction were adhesions only (n = 1), DIOS only (n = 2), and a combination of DIOS and adhesions (n = 4). Adhesiolysis was performed in the 5 patients with adhesions, and a small bowel resection was also performed in 1 patient. DIOS was treated by milking secretions distally without an enterotomy (n = 3) with an enterotomy and primary closure (n = 1) or with an end ileostomy and mucus fistula (n = 2). Five had recurrent DIOS early postoperatively. One resolved with intestinal lavage, 2 were treated successfully with hypaque disimpaction, and 2 underwent reoperation; 1 required an ileostomy. The most important risk factor for posttransplant obstruction was a previous major abdominal operation. Obstruction occurred in 7 of 18 (39%) who had undergone a prior laparotomy versus 0 of 52 who had not (P < .001, chi2). CONCLUSIONS (1) The incidence of intestinal obstruction is high after lung transplantation in children with CF. (2) Previous laparotomy is a significant risk factor. (3) Recurrent obstruction after surgery for this condition is common. (4) Preventive measures such as pretransplant bowel preparation and early postoperative bowel lavage may be beneficial in these patients.

Trauma stat and trauma minor: are we making the call appropriately?

Objectives: Trauma accounts for a significant number of pediatric emergency room visits and is the leading cause of death in pediatric patients over 1 year of age. To provide quality care, protocols are used to mobilize personnel to treat injured patients. We reviewed our experience at a level 1 pediatric trauma center, where a 2-tiered trauma activation protocol is used in treating children with significant injuries. Methods: We analyzed data in our trauma registry from 1994 to 1999 of patients with Injury Severity Score ≥ 9 in whom trauma activations were called. Data reflected demographics, severity of injury, hospital course and outcome. Trauma activations were based on standard protocols that took physiologic status, anatomic area of injury, and mechanism of injury into account. Nineteen personnel were notified in a Trauma Stat Activation, and 8 were notified in a Trauma Minor Activation. Results: There were 470 trauma activations: Trauma Stat = 220 and Trauma Minor = 250. As a group, Trauma Stat patients were more hemodynamically unstable, had a lower GCS and a higher Injury Severity Score than Trauma Minor patients. Patients in the Trauma Stat group were also more likely to require intensive care and have a prolonged hospitalization. The Trauma Stat group had a mortality rate of 20%. There were no deaths in the Trauma Minor group. Conclusions: Trauma activations result in heavy resource utilization and must be appropriate. The 2 trauma activation levels were associated with differences in injury severity, medical resource utilization, and outcome. With no deaths in the Trauma Minor group and a 20% mortality rate in the Trauma Stat group, we conclude that the protocol used was neither too conservative, nor too liberal.

Pediatric surgery on YouTube™: Is the truth out there?

BACKGROUND/PURPOSE In 2000, we described the variability of pediatric surgical information on the Internet. Since then, online videos have become an increasingly popular medium for education and personal expression. The purpose of this study was to examine the content and quality of videos related to pediatric surgical diagnoses on the Internet. METHODS YouTube™ was searched for videos on gastroschisis, congenital diaphragmatic hernia, pediatric inguinal hernia, and pectus excavatum. The first 40 English language videos for each diagnosis were reviewed for owner and audience characteristics, content and quality. RESULTS A small majority of videos were made by medical professionals (50.63%, vs. 41.25% by lay persons and 8.13% by fundraising organizations). Eighty percent of videos were intended for a lay audience. Videos by medical professionals were more accurate and complete than those posted by lay persons. CONCLUSIONS The YouTube™ videos varied significantly in content and quality. Videos by lay persons often focused on the emotional aspect of the diagnosis and clinical course. Videos by members of the medical profession tended to be more complete and accurate. These findings underscore the continued need for high quality pediatric surgical information on the Internet for patients and their families.

Laparoscopic versus Open Surgery for Malrotation Without Volvulus

Purpose: We wished to determine the risks and benefits of laparoscopic surgery when compared to the standard open approach in the management of children with malrotation without volvulus. Patients and Methods: Eighteen children undergoing laparoscopic surgery were compared to 20 similar children having open surgery during the same time period (1994-1999). Results: Three laparoscopic cases were converted. Six (33%) laparoscopic patients were found to have a broad-based mesentery at laparoscopy, and underwent appendectomy alone. The rest went on to a Ladd procedure. Eight (40%) open patients were found intraoperatively to have a broad-based mesentery. The laparoscopic group required less narcotic, was faster to full feeds, and had a shorter mean postoperative stay. On followup, there were no late complications in the laparoscopic group, but 2 (10%) open surgery patients developed adhesive small bowel obstruction. There were no cases of late volvulus following either laparoscopic or open surgery. Conclusion:...

An analysis of pediatric gunshot wounds treated at a Level I pediatric trauma center

BACKGROUND We reviewed the incidence and injury severity of children with gunshot wounds (GSWs) at our hospital. METHODS We compared trauma registry, emergency unit (EU), and admissions data from January 1993 to June 1996 (period I) and July 1996 to December 1999 (period II). Outcome measures included EU disposition (death, immediate operation, pediatric intensive care unit, ward), injury severity, mortality, and injury cause (accidental, intentional). RESULTS We treated 437 children for GSWs in the EU, with 238 (54%) admissions and 199 discharges. Comparing period I versus period II, patients treated declined from 288 to 149 (-52%, p < 0.001), and admissions decreased from 159 to 79 (-50%, p < 0.001). Injury severity increased from 35% to 57% (p < 0.001). Patients requiring immediate operations increased from 20% to 42% (p < 0.001). Direct ward admissions declined from 65% to 43% (p < 0.001). Deaths occurred in 3% of patients in both time periods. Accidental and intentional GSWs were evenly divided. CONCLUSION An alarming number of children, an average of 62 children annually, were treated for GSWs at our hospital. Despite a 52% reduction in GSWs, the percentage of severely injured patients increased by 63%. These data emphasize the importance of prevention, education, early assessment, and operative treatment.