A platform for rapid patient-derived cutaneous neurofibroma organoid establishment and screening.

Localized cutaneous neurofibromas (cNFs) are benign tumors that arise in the dermis of patients affected by neurofibromatosis type 1 syndrome. cNFs are benign lesions: they do not undergo malignant transformation or metastasize. Nevertheless, they can cover a significant proportion of the body, with some individuals developing hundreds to thousands of lesions. cNFs can cause pain, itching, and disfigurement resulting in substantial socio-emotional repercussions. Currently, surgery and laser desiccation are the sole treatment options but may result in scarring and potential regrowth from incomplete removal. To identify effective systemic therapies, we introduce an approach to establish and screen cNF organoids. We optimized conditions to support the ex vivo growth of genomically diverse cNFs. Patient-derived cNF organoids closely recapitulate cellular and molecular features of parental tumors as measured by immunohistopathology, methylation, RNA sequencing, and flow cytometry. Our cNF organoid platform enables rapid screening of hundreds of compounds in a patient- and tumor-specific manner.

Diffuse Venous Malformations of the Upper Extremity (Bockenheimer Disease): Diagnosis and Management.

BACKGROUND: Diffuse venous malformations that involve all tissues in the upper limb and ipsilateral chest wall are known as "phlebectasia of Bockenheimer." The authors describe their experience with management of this uncommon vascular anomaly. METHODS: The authors' Vascular Anomalies Center registry comprised 18,766 patients over a 40-year period. This review identified 2036 patients with venous malformations of the extremities (10.8 percent), of whom only 80 (0.43 percent) had Bockenheimer disease. The authors retrospectively analyzed patient characteristics, diagnostics, treatments, and complications. RESULTS: The venous malformation was first noted at birth or within the first few years of life with slow and gradual progression. Pain was related to engorgement of the limb. Thromboses and phleboliths were common, but diffuse intravascular coagulopathy occurred in only 12 patients (15 percent). Skeletal involvement was demonstrated as lytic lesions, cortical scalloping, osteopenia, and pathologic fractures. Management included compression garments (100 percent), sclerotherapy (27.5 percent), and resection of symptomatic areas in 35 percent of patients. Adjunctive pharmacologic medication was given in 7.5 percent. Following resection, 17 patients (60 percent) had one or more complications: hematoma, wound dehiscence, flap loss, contracture, and psychosis. There were no deaths. Symptoms improved in all patients with useful functional outcomes. CONCLUSIONS: The decision to pursue compression, sclerotherapy, pharmacologic treatment, or resection alone or in combination was made by an interdisciplinary team. Although extensive venous malformations cannot be completely ablated, debulking of symptomatic regions, resection of neuromas, and noninvasive treatments improve the quality of life. Despite the bulk and weight of the arm, forearm, and hand, and the ominous appearance on magnetic resonance imaging, these patients remain functional. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

Microvascular Hepatic Artery Anastomosis in Pediatric Living Donor Liver Transplantation: 73 Consecutive Cases Performed by a Single Surgeon.

BACKGROUND: Living donor liver transplantation is an important strategy of procuring segmental liver allografts for pediatric patients with liver failure, as suitably sized whole donor organs are scarce. The early pediatric living donor liver transplantation experience was associated with high rates of hepatic artery thrombosis, graft loss, and mortality. Collaboration with microsurgeons for hepatic artery anastomosis in pediatric living donor liver transplantation has decreased rates of arterial complications; however, reported outcomes are limited. METHODS: A 14-year retrospective review was undertaken of children at the authors' institution who underwent living donor liver transplantation with hepatic artery anastomosis performed by a single microsurgeon using an operating microscope. Data were collected on demographics, cause of liver failure, graft donor, vessel caliber, vessel anastomosis, arterial complications, and long-term follow-up. RESULTS: Seventy-three children with end-stage liver failure underwent living donor liver transplantation with microvascular hepatic artery anastomosis. The commonest cause for liver failure was biliary atresia (63 percent). A total of 83 end-to-end hepatic artery anastomoses were completed using an operating microscope. Hepatic artery complications occurred in five patients, consisting of three cases of kinked anastomoses that were revised without complications and two cases of hepatic artery thrombosis (3 percent), of which one resulted in graft loss and patient death. Patient survival was 94 percent at 1 year and 90 percent at 5 years. CONCLUSIONS: Microvascular hepatic artery anastomosis in pediatric patients undergoing living donor liver transplantation is associated with a low hepatic artery complication rate and excellent long-term liver graft function. Collaboration between microsurgeons and transplant surgeons can significantly reduce technical complications and improve patient outcomes. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Lengthening Temporalis Myoplasty for Single-Stage Smile Reconstruction in Children with Facial Paralysis.

BACKGROUND: Free muscle transfer for dynamic smile reanimation in facial paralysis is not always predictable with regard to cosmesis. Hospital stays range from 5 to 7 days. Prolonged operative times, longer hospital stays, and excessive cheek bulk are associated with free flap options. Lengthening temporalis myoplasty offers single-stage smile reanimation with theoretical advantages over free tissue transfer. METHODS: From 2012 to 2014, 18 lengthening temporalis myoplasties were performed in 14 children for smile reconstruction. A retrospective chart review was completed for demographics, operative times, length of hospital stay, and perioperative complications. RESULTS: Fourteen consecutive patients with complete facial paralysis were included. Four patients underwent single-stage bilateral reconstruction, and 10 underwent unilateral procedures. Diagnoses included Möbius syndrome (n = 5), posterior cranial fossa tumors (n = 4), posttraumatic (n = 2), hemifacial microsomia (n = 1), and idiopathic (n = 2). Average patient age was 10.1 years. Average operative time was 410 minutes (499 minutes for bilateral lengthening temporalis myoplasty and 373 for unilateral lengthening temporalis myoplasty). Average length of stay was 3.3 days (4.75 days for bilateral lengthening temporalis myoplasty and 2.8 for unilateral lengthening temporalis myoplasty). Nine patients required minor revisions. CONCLUSIONS: Lengthening temporalis myoplasty is a safe alternative to free tissue transfer for dynamic smile reconstruction in children with facial paralysis. Limited donor-site morbidity, shorter operative times, and shorter hospital stays are some benefits over free flap options. However, revisions are required frequently secondary to tendon avulsions and adhesions. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Refractory Kaposiform Hemangioendothelioma Associated with the Chromosomal Translocation t(13;16)(q14;p13.3).

We report a 7-year-old male with a history of recurrent kaposiform hemangioendothelioma (KHE) in the sacral area and multiple thoracic vertebral lesions. Tumor karyotyping revealed the balanced translocation t(13;16)(q14;p13.3). He had mildly decreased platelet counts but never experienced any episodes of Kasabach-Merritt phenomenon. He was treated with vincristine for 1 year but improvement was minor. Significant clinical improvement was seen with sirolimus therapy. To the best of our knowledge, this is the first report to demonstrate that KHE is associated with a clonal karyotypic abnormality.

Efficacy of doxycycline and sodium tetradecyl sulfate sclerotherapy in pediatric head and neck lymphatic malformations.

OBJECTIVES: Lymphatic malformations are congenital vascular anomalies that occur from abnormal development of the lymphatic channels. Studies have shown that sclerotherapy can be a reliable alternative to surgery. The purpose of this retrospective study is to evaluate the safety and efficacy of percutaneous sclerotherapy with doxycycline and 3% Sotradecol as primary treatment for pediatric head and neck LMs, and to assess outcomes based on lesion classification, location and sclerosant used. STUDY DESIGN: This study was a single center, retrospective, case series study. MATERIALS AND METHODS: The medical records of 38 children who underwent percutaneous sclerotherapy of LMs in the head and neck region at our tertiary care center between 1/1/2006 and 1/31/2011 were reviewed. A mean average of 2.9 (range 1-10) sclerotherapy sessions per child were performed. LMs involved primarily the face (61.3%), posterior neck (48.4%), submental area (45.2%), and anterior neck (35.5%). RESULTS: Twenty-nine subjects had adequate follow-up data, with 51.7% demonstrating complete resolution, 27.6% moderate improvement, and 20.7% no response. There was no significant difference in the outcome based on the sclerosant agent used or location of the lesion. Lesion type did affect outcome and macrocystic lesions were found to have a significantly higher resolution rate (95.2%) than microcystic or mixed lesions (p < 0.05). The total number of complications was similar between agents and all were minor. CONCLUSION: Our results indicate that percutaneous therapy with doxycycline and Sotradecol is safe and effective for children with LMs of the head and neck. Better outcomes were observed with macrocystic LMs. LEVEL OF EVIDENCE: 4.

Facial paralysis reconstruction in children and adolescents with central nervous system tumors.

Facial paralysis remains a vexing problem in the treatment of posterior cranial fossa tumors in children. Fortunately, current techniques are available to reconstruct the paralyzed face in restoring balance, symmetry, and amelioration of functional sequelae. The restoration of structure and function of the paralyzed face is tantamount to proper social integration and psychosocial rehabilitation. In addition, the facial nerve is important in preventing drying of the eyes, drooling, and speech abnormalities, among other functions. The most visible evidence of facial paralysis is stark asymmetry, especially with animation. This is perhaps the most troubling aspect of facial paralysis and the one that leads to the greatest amount of psychosocial stress for the child and family members. Management strategies include early and late intervention. Early reconstructive goals focus on preservation and strengthening of intact motor end plates through native stimulatory pathways. Late reconstructive efforts are centered on surgically reconstructing permanently lost function based on each third of the face. Use of adjunct modalities such as chemical or surgical denervation and myectomies are also critical tools in restoring symmetry. Physical therapy plays a large role in both early and late facial nerve paralysis in optimizing cosmetic and functional outcome.

Two-stage distraction lengthening of the forearm.

Single-stage lengthening of the forearm using callus distraction is well described; however, forearm lengthening using a 2-stage technique of distraction followed by bone grafting has received less attention. A 2-staged technique can be a better alternative in cases where the surgeon desires extensive lengthening. A retrospective review was undertaken of eleven 2-stage forearm lengthening procedures performed by 1 surgeon over a 15-year period. Indications were radial longitudinal deficiency (8 patients), neonatal ischemic contractures (2 patients), and septic growth arrest (1 patient). Average follow-up was 2.8 years. Distraction was performed on patients an average of 82 mm over an average duration of 24 weeks. Average time to union from the time of distractor removal and grafting was 87 days. Average healing index was 32.1 d/cm. Distraction problems were common and related to the length of time that the distractor was in place; they included pain, pin-related infections, and multiple mechanical device difficulties. Three patients had nonunion, and another had delayed union; however, additional procedures resulted in ultimate bony union in all patients. Demineralized bone matrix and autologous corticocancellous bone grafts yielded predictable healing and good functional results in short-distance distractions. For longer distractions, free vascularized fibula transfer produced the best outcomes. Intercalary cortical allografts did not heal well. Patients with neonatal Volkmann contractures had the most difficulty with distraction and healing, ultimately obtaining little to no lengthening and poor functional outcomes.

The nance obturator, a new fixed obturator for patients with cleft palate and fistula.

In patients with fistulas that impair function (e.g., feeding, resonance, intelligibility), obturators are used to improve feeding and reduce nasal air emission by occluding the abnormal opening between the oral and nasal cavities. This report describes a novel method for occluding an anterior palatal fistula in patients with cleft palates. The new design for a fixed obturator is based on the Nance appliance, which was originally used as a space maintainer, but has been redesigned for closing an anterior palatal fistula in a patient with cleft lip and palate. The Nance obturator may be used when the surgical closure of the fistula is not feasible and a removable device is not successful. As it is a fixed device, it does not require remaking with maxillary growth. The new design may also function as a fixed space maintainer to preserve molar anchorage and maxillary transverse width.

Colonic venous malformation and portal hypertension: association, management, and review of the literature.

We present a case of an adolescent with lower gastrointestinal bleeding caused by a colorectal venous malformation (VM) with concomitant portal hypertension. After an episode of massive gastrointestinal bleeding, we performed an extended right hemicolectomy and resection of the VM and selective portosystemic shunt. Here, we present the case and review the literature regarding portal hypertension and gastrointestinal vascular malformations. Additionally, we discuss the physiologic and hemodynamic effects of gastrointestinal vascular malformations on the portal system.

Perirectal arteriovenous malformation treated by angioembolization and low anterior resection.

We present a case of a child with ongoing lower gastrointestinal bleeding caused by a rectosigmoid arteriovenous malformation. To reduce perioperative bleeding, we performed preoperative angioembolization followed by subsequent resection by low anterior resection. Here we present the case and review the literature regarding neoadjuvent embolization for gastrointestinal and pelvic arteriovenous malformations.

Hepatic artery microvascular anastomosis in pediatric living donor liver transplantation: a review of 35 consecutive cases by a single microvascular surgeon.

Early experience with living donor liver transplantation (LDLT) was often complicated by hepatic artery thrombosis (HAT), a devastating complication resulting in graft loss. Attempting to reduce the incidence of HAT, we undertook a retrospective review of all children at our institution undergoing LDLT between March 2000 and August 2007, with the hepatic artery anastomosis performed by a single microvascular surgeon. Transplant surgeons performed the remainder of the operation. Patient outcomes were evaluated, including 1-year arterial and biliary complications, as well as overall survival. End-to-end hepatic arterial anastomoses were performed in 35 patients (median age: 15 months). Median posttransplant follow-up was 39 months (range: 0 to 90 months). One patient with a diffuse coagulopathy was retransplanted for HAT; this patient also demonstrated portal and hepatic vein thromboses. Biliary complications occurred in seven patients: three leaks, one cholangitis, one nonspecific dilatation, and two strictures. The median posttransplant follow-up was 39 months (range: 0 to 90 months). One- and 5-year patient survival was 94% and 94%, respectively. Very low rates of HAT can be achieved with LDLT using microsurgical techniques for hepatic arterial anastomoses. Outstanding long-term liver graft function can be achieved after LDLT when plastic surgeons and transplant surgeons collaborate together to reduce technical complications.