An appraisal of technical variant grafts compared to whole liver grafts in pediatric liver transplant recipients: Multicenter analysis from the SPLIT registry.

BACKGROUND: Shortages of liver allografts for children awaiting transplantation have led to high LT waitlist mortality. Prior studies have shown that usage of TVG can reduce waiting time and waitlist mortality, but their use is not universal. We sought to compare patient and graft survival between WLG and TVG and to identify potential associated risk factors in a contemporary pediatric LT cohort. METHODS: We performed a retrospective analysis of patient survival, graft survival, and biliary and vascular complications for LT recipients <18 years old entered into the Society of Pediatric Liver Transplantation prospective multicenter database. RESULTS: Of 1839 LT recipients, 1029 received a WLG and 810 received a TVG from either a LD or a DD. There was no difference in patient survival or graft survival by graft type. Three-year patient survival and graft survival were 96%, 93%, and 96%, and 95%, 89%, and 92% for TVG-LD, TVG-DD, and WLG, respectively. Biliary complications were more frequent in TVG. Hepatic artery thrombosis was more frequent in WLG. Multivariate analysis revealed primary diagnosis was the only significant predictor of patient survival. Predictors for graft survival included time-dependent development of biliary and vascular complications. CONCLUSIONS: There were no significant differences in patient and graft survival based on graft types in this North American multi-center pediatric cohort. Widespread routine use of TVG should be strongly encouraged to decrease mortality on the waitlist for pediatric LT candidates.

Predictors of survival following liver transplantation for pediatric hepatoblastoma and hepatocellular carcinoma: Experience from the Society of Pediatric Liver Transplantation (SPLIT).

Management of unresectable pediatric hepatoblastoma (HB) and hepatocellular carcinoma (HCC) remains challenging. The Society of Pediatric Liver Transplantation (SPLIT) database was used to study survival predictors in pediatric liver transplantation (LT) for HB and HCC. Event-free survival (EFS), associated risk factors, and postoperative complications were studied in children requiring LT for HB/HCC at 16 SPLIT centers. Three-year EFS was 81% for HB (n = 157) and 62% for HCC (n = 18) transplants. Of HB transplants, 6.9% were PRETEXT II and 15.3% were POST-TEXT I/II. Tumor extent did not impact survival (p = NS). Salvage (n = 13) and primary HB transplants had similar 3-year EFS (62% versus 78%, p = NS). Among HCC transplants, 3-year EFS was poorer in older patients (38% in ≥8-year-olds vs 86% <8-year-olds) and those with larger tumors (48% for those beyond versus 83% within Milan criteria, p = NS). Risk of infection (HR 1.5, 95% CI 1.1-2.2, p = .02) and renal injury (HR 2.4, 95% CI 1.7-3.3, p < .001) were higher in malignant versus nonmalignant LT. Survival is favorable for pediatric HB and HCC LT, including outcomes after salvage transplant. Unexpected numbers of LTs occurred in PRE/POST-TEXT I/II tumors. Judicious patient selection is critical to distinguish tumors that are potentially resectable; simultaneously, we must advocate for patients with unresectable malignancies to receive organs.

Employment search, initial employment experience, and career preferences of recent pediatric surgical fellowship graduates: An APSA survey, part of the right child/right surgeon initiative.

BACKGROUND: APSA's Right Child/Right Surgeon Initiative addresses issues concerning patient access to appropriate pediatric surgical care and workforce distribution. The APSA Workforce Committee sought to understand the experiences and motivations of recent graduates of Pediatric Surgery Training Programs entering the workforce. METHODS: Using APSA membership databases, we identified members who completed fellowship training from 2010 to 2019. An online survey was created using Survey Monkey, and invitations to participate were sent via email. RESULTS: 144 of 447 invited participants responded (32% response rate). 91% of respondents participated in dedicated research prior to fellowship, but only 64% perform research during their employment. 23% completed an additional clinical fellowship, but only 54% currently practice within the second field. When asked to identify the top three factors used to choose a position, the most common responses were "location or geography" (71%), "available mentorship" (53%), and "compensation and benefits" (37%). Describing their first position, 77% reported working in an academic institution, 78% reported working in a metropolitan/urban area, and 55% reported working in a free-standing children's hospital. 94% participate in General Surgery resident education, and 49% are faculty within a Pediatric Surgery fellowship. Overall, 92% of respondents were able to find the type of employment position that they had wanted. CONCLUSION: In our survey the overwhelming majority of young pediatric surgeons found the type of job they desired. Most report beginning their practice in more populated, urban areas within academic institutions. Geographic location and work environment played heavily into their employment decisions. These preferences could contribute to continued disparity in access to pediatric surgeons between urban and rural America and to dilution of experience for urban surgeons. Possible solutions include alternative incentive programs for employment in less populated areas or new training models for general surgeons in rural areas to train in fundamentals of Pediatric Surgery.

Necrotizing enterocolitis totalis: High mortality in the absence of an aggressive surgical approach.

BACKGROUND: Necrotizing enterocolitis is the leading case of gastrointestinal-related morbidity in premature infants. Necrotizing enterocolitis totalis is an aggressive form of necrotizing enterocolitis, which has traditionally been managed with comfort care. Recent advances in management of short bowel syndrome have resulted in some reported long-term survival. METHODS: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, studies that reported outcomes in children with necrotizing enterocolitis totalis were identified. The definition of necrotizing enterocolitis totalis was captured along with length of follow-up, patient demographics, and outcomes. RESULTS: A total of 766 articles were screened, of which 166 were selected for full article review. Of these, 32 articles included data on 414 patients with necrotizing enterocolitis totalis. In the majority of studies (52%), necrotizing enterocolitis totalis was not defined. Aggressive surgical therapy (defined as bowel resection or fecal diversion) was undertaken in 32 patients (7.7%), with a mortality rate of 68.8%. In contrast, nonaggressive surgical therapy was undertaken in 382 patients (92.3%), and the mortality in these patients was 95%. Long-term outcomes for necrotizing enterocolitis totalis survivors, such as length of time on parenteral nutrition, progression to liver and/or small bowel transplant, and quality of life, were not reported. CONCLUSION: We found that there is no accepted definition of necrotizing enterocolitis totalis. Aggressive surgical therapy is rarely pursued, which likely drives the overall high mortality rate. This study underscores the importance of standardizing the definition of necrotizing enterocolitis totalis and capturing short and long-term outcomes prospectively. With more aggressive surgical therapy, more infants are likely to survive this abdominal catastrophe, which was once thought to be uniformly fatal.

Extracorporeal Membrane Oxygenation in a Pediatric Patient with Hepatopulmonary Syndrome and Interrupted Inferior Vena Cava After Living Related Liver Donation.

Extracorporeal membrane oxygenation (ECMO) is used for cardiopulmonary dysfunction. Hepatopulmonary syndrome (HPS) occurs in the setting of liver failure and may cause hypoxemia. Previous reports have described the use of ECMO for HPS after liver transplant. Our patient is a 19-month-old female with biliary atresia, an interrupted inferior vena cava, and HPS on 8 liters per minute of high-flow oxygen. Following liver transplantation, her postoperative course was complicated by severe hypoxemia requiring ECMO. Due to her interrupted inferior vena cava, our standard bi-caval cannula could not be used. Hence, a 16-French double lumen venovenous right internal jugular to right atrial cannula was used to provide extracorporeal life support. She was decannulated after 17 days, remained intubated for 2 days, and weaned to room air over the next 3 weeks. This is the third pediatric liver transplant patient supported with ECMO identified in the literature, and the youngest and smallest of those reported. This approach to cannulation is unique because of the use of a double lumen venovenous cannula for HPS in a child, selected due to complex anatomy. Posttransplant ECMO may provide pediatric patients with HPS and posttransplant hypoxemia a period of support for their pulmonary remodeling and recovery from HPS.

Congenital spigelian hernia and ipsilateral cryptorchidism: raising awareness among urologists.

Spigelian hernias (SHs) are rare in the pediatric population. Although pediatric general surgeons often treat this defect, the increased association between a congenital SH and an ipsilateral undescended testis suggests that urologists may be the first provider encountering this entity. Knowledge of this condition is therefore important. We report one such case of a male infant referred to urology for an undescended testicle. Further investigation revealed the testicle to be within a congenital SH sac. Herein, we additionally review the literature concerning SHs associated with ipsilateral undescended testicles.

The use of intraabdominal tissue expanders as a primary strategy for closure of giant omphaloceles.

BACKGROUND: Giant omphaloceles present a unique challenge to pediatric surgeons because of the difficulty in obtaining timely, tension-free closure of tissues over the defect. Reports of the use of tissue expanders in the subcutaneous space, intramuscular space, or intraabdominal cavity have illustrated the usefulness of this technique to provide biologic closure of abdominal wall defects. However, these reports have focused on use of tissue expanders as a second-line treatment after other options, such as silastic silos or attempted primary closure, have failed. METHODS: We report 2 cases in which intraabdominal tissue expanders were used as a primary strategy to obtain closure of giant omphalocele defects. CASE REPORTS: The first patient was a baby boy born at 36 weeks by date who was prenatally diagnosed with a giant omphalocele. An intraabdominal tissue expander was placed at 2 weeks of age. The tissue expander was removed and his abdomen was primarily closed at 8 weeks of age. The second patient was born at 25 weeks gestation as part of a twin gestation with severe intrauterine growth retardation (600 g birth weight). Bedside reduction was not attempted because of severe pulmonary hypertension and significant loss of abdominal domain because of herniated liver and bowel. At 8 months of age, she underwent laparoscopically assisted placement of an intraabdominal tissue expander. At 9 months of age, the tissue expander was removed, all abdominal viscera were reduced, and the defect was closed using only an 8 x 8-cm piece of AlloDerm (LifeCell, Branchburg, NJ). Both children are currently at home and doing well. CONCLUSIONS: We believe that early use of intraabdominal tissue expanders provides a more expedient method of obtaining closure of the defect in giant omphaloceles.

Dual localization technique for thoracoscopic resection of lung lesions in children.

BACKGROUND: Thoracoscopic wedge resection has gained widespread acceptance as a method of resecting pulmonary metastases in pediatric cancer patients. This is most successful for lesions on the pleural surface that can be identified without palpation. Deeper lesions can be marked by preoperative computed tomography (CT)-guided techniques, but neither needle localization nor dye injection alone is foolproof. In this paper, we present our experience with a dual localization technique. METHODS: Under CT guidance, a 20-G needle is advanced to within 1 cm of the lesion and 0.1 mL of methylene blue: Low osmolar contrast (4:1 ratio) is injected. A Kopans breast biopsy hook wire is then introduced through the needle and its tip placed within the lesion. Its tail is cut flush with the chest wall. The patient is transferred to the operating room, and a wedge resection around the hook wire is performed thoracoscopically. RESULTS: Six deep pulmonary metastatic lesions were preoperatively localized in 4 pediatric patients (ages, 6-17).Median localization time was 30 minutes. All lesions were successfully marked and identified at operation.Margin-free resection of the lesion was successful in all cases. CONCLUSIONS: Thoracoscopic resection of metastatic pulmonary lesions in children, using preoperative localization with both wire localization and methylene blue/contrast injection, is safe and effective. This method allows the successful localization of lesions, even in the event of either dislodgement of the wire or over infusion of the methylene blue dye.

Timing, route, and dose of administration of heparin-binding epidermal growth factor-like growth factor in protection against intestinal ischemia-reperfusion injury.

PURPOSE: We have previously demonstrated that heparin-binding epidermal growth factor-like growth factor (HB-EGF) is an intestinal cytoprotective agent. The current study examined whether HB-EGF is effective as salvage therapy as well as prophylactic therapy for intestinal ischemia-reperfusion (I/R) injury, whether intravenous administration is as effective as intraluminal administration, and whether increased benefits are seen with increasing dose. METHODS: Total midgut I/R injury in rats was achieved by occlusion of a first-order branch of the superior mesenteric artery for 60 minutes, followed by reperfusion for 6 hours. Rats were treated with HB-EGF 5 minutes before ischemia, halfway through the ischemic event, or 5 minutes after ischemia. Route of administration was tested by administering HB-EGF either intraluminally or intravenously. Seven different doses of HB-EGF were tested. RESULTS: Heparin-binding, EGF-like growth factor protected the intestine from injury when administered before injury and was also effective when administered during ischemia or even after injury. Intraluminal administration of HB-EGF was superior to intravenous administration. Increasing doses of HB-EGF resulted in a greater cytoprotective effect. CONCLUSION: These data demonstrate that HB-EGF acts as an effective intestinal cytoprotective agent when administered intraluminally not only before injury, but also during injury and, most importantly, even after intestinal injury has already occurred. These findings support a basis for the prophylactic use of intraluminal HB-EGF in high-risk patients, as well as for the administration of HB-EGF to salvage patients in whom an intestinal insult has already occurred.

The pediatric burn unit: a profit center.

BACKGROUND: Establishment of a pediatric burn center represents a major commitment of resources. The impact of a Pediatric Burn Unit on the finances of a children's hospital has never been reported and was the purpose of this study. METHODS: Burn registry data for patients discharged from our Pediatric Burn Unit from 2000 to 2002 were integrated with financial and administrative data. Reimbursement was determined by calculating expected payments for each patient. The relationship between percent total body surface area (TBSA) burned and profit/loss margin was evaluated using regression analysis. RESULTS: During the study period, 264 pediatric burn patients were admitted to our burn service. One hundred forty-three (54%) had less than 10% TBSA burned, and their average loss margin was -179.03 dollars per patient. The 121 patients (46%) who had greater than 10% TBSA burned had an average profit margin of +349.68 dollars per patient (P =.22, SE+ 605.03) Patients treated operatively (49; 18%) had a profit margin of +2237.77 dollars per patient, whereas patients treated nonoperatively (215; 81%) had a profit margin of -432.30 dollars per patient (P =.0007, SE +249.65) The overall profit margin was +63.88 dollars per patient. CONCLUSIONS: Our pediatric burn service covered all hospital fixed costs and made a small profit. Pediatric burn care can be a profit center for children's hospitals. Investment in a Pediatric Burn Program provides adequate financial return for the hospital.

CT scans may not reduce the negative appendectomy rate in children.

BACKGROUND/PURPOSE: Concern about an increased lifetime risk of cancer in children who have undergone a single computed tomography (CT) scan prompted us to review utilization of this diagnostic test in our appendicitis population. METHODS: From 1998 to 2001, the records of 720 children admitted to our hospital with a diagnosis of appendicitis were reviewed for adjunct diagnostic modalities, including ultrasonography (USG) and CT scanning. Negative appendectomy rates were determined by the final pathologic report. Statistical comparisons were made using the chi(2) test, and significance was assigned at P <.05. RESULTS: The use of ultrasound scan for diagnosing appendicitis decreased from 20.0% in 1998 to 7.0% in 2001 (P <.01). Conversely, the use of CT scans increased from 17.6% in 1998 to 51.3% in 2001 (P <.001). During this time period the difference in the negative appendectomy rate was not statistically significant (P < 0.20). Of the negative appendectomies, 11 of these patients had a USG interpreted as positive for appendicitis (22.0%), and 9 had a CT scan interpreted as positive (18.0%). CONCLUSIONS: Liberal use of CT scans in diagnosing appendicitis in children has not resulted in a decreased negative appendectomy rate. Potentially harmful radiation exposure should prompt pediatric surgeons to reevaluate the role of CT scanning in the management of children with suspected appendicitis.

Upregulation of endogenous heparin-binding EGF-like growth factor (HB-EGF) expression after intestinal ischemia/reperfusion injury.

Expression of endogenous heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF), a proven intestinal cytoprotective molecule, was examined in intestinal epithelial cells (IEC) in vitro, and in intestine undergoing ischemia/reperfusion (I/R) injury in vivo. In vitro, cells were exposed to anoxia for 90 min followed by reoxygenation for 1-3 h (A/R). In vivo, total midgut I/R injury was produced in rats by occlusion of the superior mesenteric artery for 30 or 90 min followed by reperfusion for 4 h. In situ hybridization and immunohistochemistry were used to study HB-EGF mRNA expression and protein production. In vitro, normal IEC had no detectable HB-EGF mRNA or protein expression. After anoxia, cells expressed HB-EGF mRNA and protein, with expression reaching a peak 2-3 h after reoxygenation. In vivo, only very low levels of HB-EGF mRNA and no detectable protein were found in normal intestine. Four hours after I/R, HB-EGF protein was detected in villous epithelia subjected to 30 min but not 90 min of ischemia, whereas HB-EGF mRNA was highly expressed after both ischemic intervals. Endogenous HB-EGF is immediately upregulated in IEC after A/R injury and in intestine after I/R injury. Thus, HB-EGF acts as an immediate early gene under these conditions.

Heparin-binding EGF-like growth factor downregulates expression of adhesion molecules and infiltration of inflammatory cells after intestinal ischemia/reperfusion injury.

BACKGROUND/PURPOSE: This study examined whether heparin-binding epidermal growth factor (EGF) like growth factor (HB-EGF), a proven intestinal cytoprotective molecule, exerts its protective effects through modulation of adhesion molecule expression and inflammatory cell infiltration, important pathogenic mediators of ischemia/reperfusion (I/R) injury. METHODS: Total midgut I/R injury in rats was achieved by occlusion of the superior mesenteric artery for 90 minutes followed by reperfusion. Rats were treated intraluminally with 600 microg/kg HB-EGF or with PBS 45 minutes after the onset of ischemia. Four- or 24-hours post-I/R, ileum was harvested and processed for immunhistochemical detection of P-/E-selectins, intercellular adhesion molecule-1 (ICAM-1)/vascular cell adhesion molecule-1 (VCAM-1), and polymorphonuclear cells (PMN)/macrophages (MPhi). RESULTS: P-/E-selectins were significantly induced in vascular endothelia 4 hours after I/R injury compared with normal intestine. HB-EGF treatment significantly down-regulated the expression of P-/E-selectins. I/R-injured intestine displayed overexpression of ICAM-1 and VCAM-1, which were significantly down-regulated by HB-EGF treatment. Lastly, I/R injury caused significant infiltration of PMN and MPhi into wounded tissue 24 hours after I/R compared with normal intestine. HB-EGF treatment significantly decreased PMN and MPhi infiltration into the injured tissue. CONCLUSIONS: HB-EGF intestinal cytoprotection is mediated, in part, by down-regulation of expression of adhesion molecules and infiltration of PMN and MPhi after intestinal I/R injury.

Heparin-binding EGF-like growth factor preserves crypt cell proliferation and decreases bacterial translocation after intestinal ischemia/reperfusion injury.

BACKGROUND/PURPOSE: Heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF), a known mitogenic, chemotactic, and cytoprotective growth factor for epithelial cells, was examined to see whether it could protect intestinal barrier function and decrease bacterial translocation (BT) after ischemia/reperfusion (I/R) injury. METHODS: In vitro, tight junctional integrity of intestinal epithelial cells (IEC-6) cells was evaluated by measuring transepithelial electric resistance (TEER), and monolayer permeability was evaluated by translocation of Escherichia coli C25. In vivo, crypt cell proliferation was assessed by 5-bromodeoxyuridine incorporation with calculation of a proliferative index (PI), and BT was evaluated by culture of mesenteric lymph nodes. RESULTS: In vitro, anoxia damaged tight junctional integrity and increased permeability of IEC-6 cell monolayers, events that were reversed completely by treatment of the cells with HB-EGF. Twenty-four hours after I/R injury in vivo, crypt cell proliferation index (PI) decreased significantly from 35.6 +/- 4.5 to 17.8 +/- 3.4. Administration of HB-EGF preserved crypt cell activity with PI of 34.9 +/- 4.1, similar to that of normal ileum. None of the normal or sham-operated animals showed BT, whereas BT occurred in 87.5% of I/R-injured rats. In animals exposed to I/R but treated with HB-EGF, BT was decreased significantly to 12.5%. CONCLUSION: HB-EGF preserves proliferation of crypt cells, maintains integrity of epithelial cells, and subsequently decreases enteric BT after I/R injury.