PSU Volume 61 NO 01 JULY 2023

Rhabdomyosarcoma Update

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in infants and children representing about 5% of all cases of childhood cancer. The third most common extracranial solid tumor in children after Wilms tumor and neuroblastoma with 6 new cases per one million population per year. RMS has two age peak incidence, between 2 and 6 years, and a second surge during early adolescence (10-18 years). Head, neck and pelvic malignancies are more prevalent in infancy and early childhood, while trunk, extremity and paratesticular RMS is largely a disease of adolescents. RMS arises is a malignant tumor of mesenchymal tissue included in the group of small blue round cell tumors occurring at almost any body site (excluding brain & bone). RMS has two major histological subtypes: embryonal and alveolar. The predominant histologic type in infants and small children is embryonal affecting head, neck, and genitourinary location. Botryoid RMS is a subtype of the embryonal variety, which ordinarily extends into body cavities such as bladder, nasopharynx, vagina, or bile duct. The alveolar cell type, named for a superficial similarity to the pulmonary alveoli, is the most common form found on the muscle masses of the trunk and extremities, and is seen more frequently in older children. Most RMS are sporadic, while a few are associated with familial syndromes such as Li-Fraumeni, DICER1 syndrome and neurofibromatosis type 1. Histologically, embryonal RMS is found in 75% of patients and alveolar in 25%. Embryonal RMS is characterized by loss of heterozygosity at the 11p15 locus in 80% of patients, while the alveolar RMS is associated with the FOXO1 and PAX3/PAX7 transcription factor fusion of genes associated with worse overall survival in the case of the FOXO-PAX3 fusion. Approximately 80% of tumors that are alveolar RMS carry a FOXO1 fusion, while more than 95% of embryonal RMS have no FOXO1 fusion. The presence or absence of FOXO1 fusion gene drives the clinical behavior of RMS. PAX/FOXO1 fusion status is recognized as a more important prognostic factor compared to histological subtypes that will be utilized instead of histology for risk stratification. PAX fusion is so important that RMS is subdivided into 2 major subtypes, the commonest is PAX-fusion negative RMS (previously called embryonal), occurring in 70%, and the PAX fusion-positive RMS (previously called alveolar RMS). Spindle cell/sclerosing RMS is a third subtype, whereas pleomorphic RMS occurs only in adults. Initial pre-treatment staging uses the TNM system depending on site, size, degree of tumor invasion, nodal status, and metastasis. Extent of residual disease after resection is an important prognostic factor highlighting the importance of adequate surgical resection. Once resected patients are assigned to a clinical group prior of initiating chemotherapy. Risk stratification (low, intermediate, and high) is used to tailor the intensity of adjuvant therapy and it incorporate TNM status pre-treatment, extent of disease after resection, primary tumor site and histology/fusion status into a system. For localized disease, fusion-positive patients had a 5-years survival of 52-65%, while fusion negative had survival of 78-88%.For metastatic disease, fusion-positive patients had a 5-year survival of 6-19% compared with a 46-58% fusion-negative survival. Postoperative clinical group classification is determined by extent of residual tumor, lymph nodes status and metastatic disease, and ranges from Group I (complete resection without regional node involvement), Group II (microscopic residual tumor, involved regional nodes or both), Group III (gross residual tumor after incomplete resection or biopsy), and Group IV (distant metastasis). Most RMS present as an asymptomatic mass. Standard labs, MRI and CT-scans are required including bone marrow aspirate, bone scan, CT of brain, lungs and liver and lumbar puncture of CSF collection (parameningeal tumors). PET/CT is useful in evaluation of regional adenopathy, occult metastasizes and persistent viable disease or recurrence. Determining lymph node involvement is essential as regional positive nodes are irradiated and positive distant nodes are metastatic disease. All patients with RMS receive chemotherapy based on risk group (vincristine, actinomycin-D, ifosfamide, irinotecan and cyclophosphamide). Ifosfamide has a lower gonadal toxicity when compared with cyclophosphamide but is more nephrotoxic. Low and intermediate risk children have improved outcome, while high risk fare worse. Response is measure with follow up imaging: MRI or CT after three courses of chemotherapy as complete (no tumor), good (reduced 2/3), poor (>1/3 and < 2/3), and progressive (> 1/3). Radiotherapy is used in almost all RMS children to improve local control and outcome. Radiation therapy is often utilized to improve local control in patients with Group II (microscopic residual), or Group III (gross residual) disease and in all patients with FOXO1 fusion positive tumors. Surgery is essential local treatment. The quality of resection is defined by the worst pathological margin essential for risk stratification. Surgical removal of the entire tumor should be considered initially if possible, and only if major functional or cosmetic impairment is not expected to result. The goal of surgery is complete tumor removal with normal surrounding margins (0.5 cm) and without loss of function to the child. No role for debulking tumor in RMS. If a complete resection is not possible, an open biopsy should be done. Core biopsy is not ideal due to insufficient tissue. Tumors in cavities such as bladder, prostate or vagina undergo endoscopic biopsy. Lymph node disease is present in 23% of all RMS children, predominantly in primary tumors sites such as perineum, retroperitoneum, extremity, bladder/prostate, parameningeal and paratesticular. Positive lymph node status is an independent poor prognostic factor Children requiring nodal evaluation include those with positive clinical nodes, extremity/trunk primary tumors, paratesticular patients > 10 years of age, and in patient with fusion positive alveolar RMS. If positive upon sentinel or regional node sampling (sentinel is preferred; more accurate), the lymph node bed should undergo radiation therapy. Indocyanine green has been reported to stage lymph nodes in paratesticular and extremity RMS. Complete nodal dissection does not improve outcome. Delayed primary excision can be evaluated between 9 and 12 weeks of induction chemotherapy with imaging. In a few instances mutilating surgery should be considered with insufficient response to chemotherapy. RMS is curable in most children with localized disease who receive combined modality therapy with a survival rate > 70% at 5 years of diagnosis. Approximately 15% of children with RMS present with metastatic disease and have a poor prognosis with 25% survival. 

Retained Surgical Foreign Bodies

While performing surgery many foreign bodies (FB) are utilized. After the procedure is accomplished a detailed surveillance of every FB utilized is make mandatory to avoid retaining them intracorporeally. Retained FB such as surgical sponges, gauzes and cotton material remains a clinically significant problem. In the USA 2000-4000 cases of retained FB occur yearly (around 13/100,000 cases-year). Between 1995 and 2020 retained FB at surgery was the most common sentinel event reported to the Joint Commission. Retained FB are most frequently left behind in the following surgical departments: general (18%), gynecological (13%), orthopedics (5%) and cardiac (2%). FB left in the body cavities can be divided into soft (textiles, synthetics) such as swabs, gauze, bandage, towels; and hard (needles, steel clips, surgical tools, like retractors, scissors, forceps, guidewires, or fragments). Retained FB undergo two types of foreign body reaction: 1) an aseptic silent fibrinous response resulting in calcification and decomposition incidentally discovered, and 2) inflammatory reaction that results in an abscess. During this inflammatory process pain, fistulization, perforation of viscera, raise suspicion for a malignant mass, obstructive ileus, bleeding, and bowel obstruction can occur. The retained FB can be organized as a mass inside the abdomen and a tumor may be suspected. Commonly the discovery of a retained FB after surgery occurs due to non-specific complaints. They can present as a mass usually in the abdominal cavity and are diagnosed during a routine radiological examination. If the patient complains of pain, frequent infections and a palpable mass, a retained FB should be suspected.  Almost 70% of such cases will need surgical removal of the FB. Almost 20% of patients results in small bowel fistulas, obstruction, or bowel perforation. Sponges are the most common retained FB in the human cavities of the abdomen, pelvis, or retroperitoneum. They could be for days, months or even years without producing problem. Surgical instruments such as clamps, retractors, electrodes, or drains have been left behind. Those made of stainless steel evoke minimal reactions. Most retained FB are detected in the first three weeks after surgery, with one-fourth detected after 60 days. There are two principal factors that could explained the occurrence of retained FB in surgery. The 1st factor is procedure related including urgent procedures, multiple, complex, or lengthy procedures and obese patients. The second factor pertains to process related risk factor commonly related to surgery personnel changes during the surgical procedure, less than strict adherence to preoperative and postoperative device counts and inconsistency policies regarding use of intraoperative imaging. Some other risk factors associated with retained FB are inadequate intraoperative surveillance radiography due to poor technique when a suspicion of a retained FB is established in the operating room, failure to fully document and communicate the radiographic findings, inadequate intraoperative films because of patient body habitus such as morbid obesity, and failure of the surgical service to communicate to the radiologist a persistently inaccurate sponge or towel count leading to failure of image interpretation. When counts are incorrect, routine surgical exploration should be undertaken and radiographs of the surgical field should be taken with previous notice to the radiologist that we are missing something. Counts should be performed at the following time points during the procedure: before the procedure begins (initial count), whenever new additional items are used during the operation, and before the surgeon closes the body cavity, when the surgeon begins to close the wound, and when the surgeon closes the skin (final count). The radiologist, which should be available for immediate discussion of the problem should locate suspected retained FB and order whatever films are necessary to rule out the problem before closing the patient. Intraoperative fluoroscopy may be used to further evaluate a specific area or density of interest seen on the portable radiographs. Whenever a high suspicion of a retained FB continues a CT scan should be performed. MRI does not reliable show foreign bodies due to the lack of signal given off by inert objects. Unintentional retained FB increase morbidity, mortality, and medicolegal complications. Best strategies to prevent retained FB are good communications in the operating room, systematic counting of materials used during the procedure, use of tracking devices for electronic sponges, bar coding scanning, radiofrequency detection, and counting before the cavity and skin are closed.   

Teduglutide

Short bowel syndrome (SBS) occurs when there is reduced functioning bowel length to sustain life. SBS can be congenital or acquired. Common causes of SBS in childhood include congenital defects of the small bowel, such as antenatal atresia, midgut volvulus, total aganglionosis, and acquired disease such as necrotizing enterocolitis, vascular thrombosis, mesenteric tumors, or abdominal trauma. In SBS the absorptive capacity of the bowel is shortened while children develop a constellation of symptoms such as diarrhea, steatorrhea, abdominal pain, malnutrition, and dehydration. SBS is the main reason why children and adults receive long-term home parenteral nutrition. Short bowel syndrome is the most common cause of intestinal failure. Long-term administration of parenteral support is lifesaving but associated with potentially life-threatening complications including intestinal failure associated liver disease, central line-associated blood stream infections, and central venous thrombosis. Therapy regimens like dietary interventions, oral rehydration, or nutrition solutions and antidiarrheals and antisecretory agents focus on optimization of the functional capacity of the remnant bowel in SBS. In 2012, teduglutide became the first approved agent for the long-term management of SBS. Glucagon-like peptide-2 (GLP-2) is a hormone secreted by enteroendocrine L cells in the distal ileum and proximal colon in response to the presence of unabsorbed luminal nutrients, is a key component of the adaptive response to intestinal malabsorption. Teduglutide is a 33-amino acids glucagon-like peptide-2 (GLP-2) analog. It contains an amino acid substitution of glycine for alanine at position 2, which renders teduglutide resistant to degradation. As a GLP-2 analog, teduglutide binds to and activate the GLP-2 receptor in the small bowel and causes release of insulin-like growth factor, nitric oxide, and keratinocyte growth factor. The result is an increase intestinal and portal blood flow, repair, and normal growth of the intestinal mucosa by increasing villi height, and crypt depth, and inhibition of gastric acid secretion and gastric motility. Teduglutide reduces intestinal losses and improves absorption by increasing the intestinal surface area and potential for increased intestinal absorption.  Teduglutide is given once daily subcutaneously at a dose of 0.05 mg/kg body weight and excreted through the kidneys. Most commonly reported adverse reactions to teduglutide include abdominal pain, injection site reactions, nausea, headaches, abdominal distension, fluid overload, stoma complications and upper-respiratory tract infections. Other events included intestinal obstruction, biliary effects, pancreatitis, pancreatic duct stenosis and pancreatic infection. Teduglutide is not recommended in patients with active cancer of the gastrointestinal tract. Teduglutide could potentially increase the absorption of oral medicines. Teduglutide is specifically indicated for patients with SBS who are dependent on parenteral nutrition. Teduglutide seems to reduce the need for parenteral nutrition in people with SBS and intestinal failure. Teduglutide has been found in phase III studies to reduce parenteral support volume, calories, and infusion time in pediatric patients with SBS and intestinal failure. By titrating plasma citrulline levels which increases with teduglutide continued treatment with teduglutide is necessary to maintain the tropic effect on the gut epithelium. In pediatric patients the maximum treatment duration has been 30 months approximately. The response rate to teduglutide treatment could be estimated as 64% at 6 months, 77% at 1 year, and 82% at more than two years with a similar weaning response rate. The presence of colon in continuity is a negative predictive factor for response but a positive predictive factor for weaning. The choice regarding treatment duration should be made individually since teduglutide discontinuation could show up a regression of effects of absorption and growth of the bowel. Enteral autonomy, meaning the complete discontinuation of parenteral solutions, remains the primary therapy goal of teduglutide treatment in children with SBS and intestinal failure. Teduglutide has FDA approval for children above the age of one year. Teduglutide is an expensive treatment option that can be cost saving in selected subgroups of patients with SBS.

PSU Volume 61 No 02 AUGUST 2023

Traumatic Aortic Rupture in Children

Traumatic aortic injury (TAI) in children is a rare but serious condition characterized by disruption of the aortic wall due to blunt thoracic trauma. Although relatively uncommon, TAI carries a high mortality rate if not promptly recognized and managed appropriately. Pediatric patients with TAI often present with challenging diagnostic and management considerations due to differences in anatomy, physiology, and injury patterns compared to adults. The true incidence of TAI in children is challenging to determine due to its rarity. However, it is recognized as a severe injury with significant morbidity and mortality. It occurs in 10% to 30% of fatalities from blunt thoracic trauma and is the second most common cause of death after head injury. Approximately 80% of affected patients do not survive to reach the hospital. TAI commonly occurs as a result of high-energy mechanisms such as motor vehicle accidents or falls from heights. Post-traumatic aortic rupture occurs mainly in motor vehicle frontal crashes with driver ejection. the most frequent anatomical position of ATAT (55?67%) is at the isthmus of the descending thoracic aorta, where the relatively immobile descending aorta, held by the ligamentum arteriosum, and overlying mediastinal pleura, decelerates at a different speed compared with the fairly mobile heart and aortic arch. The unique biomechanical properties of pediatric aortas, including greater elasticity and vulnerability to shear forces, contribute to the propensity for injury in this population. Children with TAI may present with a range of signs and symptoms, including chest pain, dyspnea, hypotension, and neurological deficits. However, clinical manifestations can be subtle or masked by associated injuries, making early diagnosis challenging. This lesion is an absolute surgical emergency. Diagnostic modalities such as chest X-ray, computed tomography angiography, and transesophageal echocardiography play a critical role in confirming the diagnosis and assessing the extent of injury. All children with confirmed aortic rupture in angiogram had widened mediastinum and blurred aortic arch. Associated systemic injuries are quite common in pediatric patients with traumatic aortic rupture including pulmonary contusion, long bones or pelvis fractures, head trauma and myocardial contusion. The management of TAI in children requires a multidisciplinary approach, involving pediatric surgeons, pediatric cardiologists, and trauma teams. Hemodynamic stability, associated injuries, and the extent of aortic injury guide the choice of management strategy. Delayed management approach with aggressive blood pressure control and serial radiological monitoring is a safe and recommended option for those with severe concomitant injuries or other medical comorbidities. Operative management options include open surgical repair, endovascular stent graft placement, or hybrid approaches. Non-operative management may be considered in select cases, particularly when there are associated injuries or significant comorbidities that increase the risk of surgery. Until definitive repair, the patient should be kept relatively hypotensive to reduce the risk of complete aortic rupture, which might lead to exsanguination. The reason for permissive hypotension is to reduce the shear forces, minimizing the risk of rupture prior to repair. In the last decade there has been a transition in the therapeutic approach from open surgical repair to endovascular repair. Advantages of endovascular treatment also include avoidance of thoracotomy, single-lung ventilation, aortic cross-clamping, left heart or cardiopulmonary bypass, spinal cord ischemia, and renal insults secondary to hypoperfusion. In pediatric patients, open repair either with primary anastomosis or placement of synthetic grafts is currently still the standard of care because not all trauma centers treat children, and the implantation of such devices needs the availability of small diameter stents together with highly skilled personnel who can safely perform the procedure. The second obstacle is the small lumen in the femoral and external iliac arteries which, for proper implantation, require prior surgical exposure of the common iliac artery. The most important anatomic characteristic of a posttraumatic lesion allowing endovascular treatment is the presence of an adequate proximal neck or at least 5 mm aortic wall from the subclavian artery with absence of mural thrombus, calcifications, or hemorrhage. The endovascular technique does not require heparinization, carries a low invasiveness with attendant minimal blood loss, and can be applied in the acute phase without the risk of destabilizing pulmonary, head, or abdominal traumatic lesions. Long-term outcomes following TAI in children are influenced by several factors, including the severity of the injury, associated injuries, and the chosen management approach. Early recognition and appropriate management significantly impact patient outcomes. Children who undergo successful repair can experience favorable long-term outcomes with low rates of complications. However, long-term surveillance is crucial to detect potential late complications, such as aortic aneurysm formation, pseudoaneurysm, or aortic valve dysfunction. Prevention of TAI in children primarily focuses on improving road safety, implementing proper restraint systems, and promoting injury prevention strategies. Continued research into the optimal diagnostic modalities, management strategies, and long-term outcomes will further enhance our understanding of TAI in children and improve patient outcomes. Despite advances in surgical and resuscitation techniques in recent years, the perioperative and postoperative mortalities associated with TRTA have remained high. In most cases, a complete transection occurs, with instantaneous death. In approximately 15% of cases, the adventitial wall and mediastinal structures contain the rupture, allowing survival. In these cases, if adequate antihypertensive therapy acting to reduce wall stress is prompt, the risk of aortic rupture is limited.

Sleeve Gastrectomy in Children

Childhood obesity has emerged as a significant public health concern, necessitating effective interventions to mitigate its long-term consequences. More than 30% of children and adolescents in the USA are overweight or obese. Morbid obesity is defined as a BMI above the 99th percentile for age and sex.  Obesity increases the risk of developing type 2 diabetes, systemic and pulmonary hypertension, obstructive sleep apnea, nonalcoholic fatty liver disease, cardiovascular disease, psychosocial difficulties, and poor quality of life with premature death. Nonsurgical weight management programs achieve modest weight loss results at best. Surgical approaches, such as sleeve gastrectomy (SG), have been considered as potential options for severely obese children. During laparoscopic sleeve gastrectomy 70-80% of the greater curvature and fundus of the stomach is removed with a stapler device. Calibration as to how much to removed uses either a gastroscope or bougie dilators in children. Complications of sleeve gastrectomy include leak, bleeding, and surgical site infections. Leak is suspected in the postoperative period when the child presents with unexplained tachycardia. Other signs might include leukocytosis, fever, and intolerance to oral feedings. Leaks are typically located just below the GE junction. Should a leak be suspected a CT of abdomen with oral/IV contrast should be performed. Extraluminal bleeding is typically from the staple line, spleen, liver, or abdominal wall which might need further surgery. With intraluminal bleeding the child might present with melena or hematemesis and can be controlled endoscopically. Most common short-term complications are nutritional deficiencies. Other late complications include stricture and gastroesophageal reflux. Several studies have demonstrated the effectiveness of sleeve gastrectomy in achieving substantial weight loss in pediatric patients. Longitudinal investigations have reported significant reductions in body mass index and excess weight loss percentage following the procedure; with 25-30% of total weight lost permanently. In addition, weight loss appears to be maintained safely and growth velocity is unaffected. Successful weight loss not only improves physical health but also has a positive impact on psychological well-being and quality of life in obese children. Sleeve gastrectomy has shown promising effects on metabolic parameters in children. The procedure has been associated with significant improvements in insulin resistance, glucose metabolism, lipid profiles, and blood pressure. Remission of type 2 diabetes, hypertension and dyslipidemia occurs in 90%, 78% and 63% of patients at three to 5 years of follow-up respectively. These favorable metabolic changes contribute to the reduction of comorbidities such as type 2 diabetes, dyslipidemia, and hypertension in obese children. While short-term outcomes of sleeve gastrectomy in children appear promising, long-term consequences and safety considerations warrant thorough evaluation. Sleeve gastrectomy in children may lead to nutrient deficiencies, specifically vitamin D, calcium, iron, and vitamin B12. This should be provided life-long. Long-term follow-up studies are necessary to assess the potential impact of these deficiencies on growth, bone health, and cognitive development in pediatric patients. Furthermore, evaluating the durability of weight loss and the potential for weight regain is essential. Long-term studies are needed to ascertain whether the benefits of sleeve gastrectomy persist into adulthood and whether patients maintain improved metabolic parameters and sustained weight loss. Addressing the psychological and behavioral aspects of obesity is critical in the management of pediatric patients. Sleeve gastrectomy has shown potential in positively influencing self-esteem, body image, and psychological well-being in children. Improved mental health outcomes contribute to long-term weight maintenance and enhanced quality of life. A multidisciplinary approach involving medical, nutritional, and psychological support is crucial in the comprehensive management of pediatric patients undergoing sleeve gastrectomy. Regular monitoring of nutritional status, including appropriate supplementation and dietary counseling, is necessary to mitigate the risk of nutrient deficiencies. Long-term follow-up is paramount to assess the sustained efficacy, safety, and potential late-onset complications of sleeve gastrectomy in children. Continued monitoring of growth, bone health, cognitive development, and psychosocial well-being is essential to ensure optimal outcomes. Sleeve gastrectomy demonstrates efficacy in achieving substantial weight loss and improving metabolic parameters in obese children. However, long-term consequences, including nutrient deficiencies, require further investigation.

Hemophilia Inhibitors in Children

Hemophilia is a rare bleeding disorder characterized by mutations in the genes encoding either coagulation factor VIII or coagulation factor IX leading to a deficiency of either factor VIII (hemophilia A) or factor IX (hemophilia B). Children with hemophilia suffer from recurrent bleeding episodes in the joints, internal bleeding including CNS bleeding. The cornerstone of hemophilia management is replacement therapy with exogenous clotting factor concentrates. One of the significant challenges in managing hemophilia is the development of inhibitors, which are neutralizing anti-drug antibodies that render factor replacement therapy ineffective Inhibitors pose a unique challenge in pediatric patients due to their higher prevalence and increased clinical impact. Inhibitors are associated with significant morbidity, including higher rate of bleeding complications, increase disability due to the development of arthropathies, and a reduced quality of life. In hemophilia A the risk for inhibitors development is approximately 30% I children with severe hemophilia. Pediatric surgeons play a crucial role in the care of hemophilia patients, especially when surgical interventions are required. Understanding the implications of hemophilia inhibitors is vital for pediatric surgeons to ensure optimal perioperative management and favorable outcomes. The development of inhibitors in hemophilia is a complex immune response resulting from genetic and environmental factors. In pediatric patients, inhibitors occur more frequently and at an earlier age compared to adults. Inhibitors can neutralize infused clotting factors, leading to a loss of therapeutic efficacy and increased bleeding risk. Patients with inhibitors often experience severe and uncontrolled bleeding episodes, which can be life-threatening and require prompt intervention. Inhibitors can also impact the success of surgical procedures, making surgical management in children with hemophilia more challenging. The detection and quantification of inhibitors in hemophilia patients involve laboratory assays, including the Bethesda assay and modified versions. These assays measure the inhibitory activity of patient plasma against a standardized clotting factor preparation. Regular inhibitor screening is recommended in pediatric hemophilia patients, particularly before surgical interventions. Understanding the inhibitor titer and its impact on clotting factor levels helps guide treatment decisions and surgical planning. Immune tolerance induction (ITI) therapy aims to eradicate inhibitors and restore normal clotting factor responses. However, ITI is challenging in children and may not always be successful. ITI therapy is preferable to treatment of inhibitors with factor VII inhibitor bypassing agents such as recombinant activated factor VII or activated prothrombin complex concentrate which has less predictable clinical hemostatic efficacy and are more expensive option. Best candidates for ITI therapy are children with recently diagnosed inhibitors. The most important predictor of ITI outcome appears to be peak inhibitors titers both pre-ITI and during ITI. Pediatric surgeons must consider several key factors when performing surgery on hemophilia patients with inhibitors. Preoperative planning involves assessing the inhibitor titer, clotting factor levels, and determining the need for inhibitor eradication strategies before surgery. Emicizumab, a monoclonal antibody that substitute the function of activated factor VIII, has been found to be very effective for the prevention of bleeding across the pediatric hemophilia age spectrum regardless of whether the patient had or did not have inhibitors. Emicizumab has become the standard of care for patients with inhibitors. Close coordination with the hemophilia treatment center is essential to optimize perioperative hemostatic management. Specialized surgical techniques, including minimally invasive approaches and local hemostatic measures, can help minimize bleeding risks during surgery. Postoperative care involves monitoring for bleeding complications, appropriate factor replacement, and rehabilitation to ensure optimal recovery. Hemophilia inhibitors in children present unique challenges for pediatric surgeons. Understanding the pathogenesis, clinical significance, diagnostic strategies, and treatment options for inhibitors is crucial for effective perioperative management. Collaboration with a specialized hemophilia treatment center and adopting tailored surgical techniques and hemostatic measures are essential for successful surgical outcomes in pediatric hemophilia patients with inhibitors. By comprehensively addressing the implications of hemophilia inhibitors, pediatric surgeons can contribute to the overall care and improved quality of life for children with hemophilia.

PSU Volume 61 No 03 SEPTEMBER 2023

Small Bowel Obstruction

Small bowel obstruction (SBO) is condition in which the intestine is obstructed due to mechanical or non-mechanical causes. Bowel obstruction accounts for more than 15% admissions for abdominal pain from the emergency department. The small bowel is involved in 60-85% of intestinal obstruction. Delay in diagnosis and treatment of SBO can result in bowel ischemia and death. Postoperative adhesion is the most common cause of SBO. Adhesive SBO occurs after abdominal surgery in 1-6.5% of pediatric patients. While more common after laparotomy, adhesive SBO also occurs after laparoscopic procedures. Excluding appendectomy which has a much lower rated of obstruction, high rates of bowel obstruction have been reported following ileostomy formation and closure, Ladd procedure for malrotation, and nephrectomy from Wilms tumor. The mean age of children admitted with adhesive SBO is 12.6 years, of which approximately 63% are males. Most frequent symptoms of SBO include crampy abdominal pain, anorexia, vomiting, and obstipation. Late signs include lethargy, constant abdominal pain, and distension. Pin-point abdominal tenderness, associated with fever and leukocytosis are worrisome findings for ischemic bowel. Children presenting with signs of bowel ischemia which include peritoneal signs, tachycardia, fever, leukocytosis, and lactic acidosis should undergo emergent laparotomy/laparoscopy. For children who do not present with signs and symptoms of ischemia, initial non-operative management of SBO include nasogastric or nasointestinal tube decompression, bowel rest, intravenous hydration and electrolyte balance maintenance. Serial abdominal examinations are performed to identify early signs of developing bowel ischemia. Success of nonoperative management depends on the extent of obstruction. In children, 40% present with signs and symptoms needing immediate laparotomy. Success rate of nonoperative treatment is 16-52%. Factors associated with need of operation include obstipation, prior SBO, number of prior operations, history of hernia, history of malignancy, thickened small bowel wall, free intraperitoneal fluid, mesenteric edema, and transition point. Serum procalcitonin is a biomarker which elevated is predictive of bowel ischemia and failure of conservative management. Imaging is generally required to confirm the diagnosis of SBO, judge the location of the obstruction, and identify the strangulated intestine.  Two-view plain radiographs are the standard imaging for the diagnosis of SBO in children. Two-view plain radiographs are the standard imaging for the diagnosis of SBO in children. Abdominal CT and US play a vital role in diagnosis. CT scan have a high sensitivity and specificity to identity the diagnosis of SBO, site and cause of the obstruction at the expense of radiation injury. Worrisome CT findings include bowel wall thickening, free peritoneal fluid, and extent of pneumatosis. The underlying cause of obstruction plays a particular role in strangulated SBO. The rate of bowel strangulation complicated by internal herniation is high.  Through multivariate analysis, four clinical signs pointing toward the need of emergency surgery include severe continuous abdominal pain, tachycardia, leukocytosis, and abdominal distension. A progression from cramping to more focal and constant abdominal pain may indicated peritoneal irritation related to bowel ischemia. Several studies have investigated the utility of water-soluble contrast challenges with agents such as Gastrograffin (or Cystografin/Omnipaque) as both therapeutic as well as a way to determine which patient might benefit from ongoing non-operative management. If the contrast material reaches the large bowel within the first 24 hours, the child is deemed to have a partial SBO and can be fed. Should the contrast fails to reach the colon in 24 hours a complete SBO is present, and the child should undergo surgery. Gastrograffin challenge use are safe with almost zero complications, decreases the length of stay among those management successfully without surgery. Its use is associated with a decrease rate of reoperation, decreased patient morbidity, shorter length of hospital stay, limited radiation exposure as fewer CT scans is performed, and fewer costs. If the SBO is due to a mass, volvulus, hernia or in a closed loop configuration, a contrast challenge should not be used. The hyperosmolar properties of these contrast agents help draw edema from the bowel wall into the lumen, improving motility and thus contributing to relief of the bowel obstruction. In the setting of early postoperative SBO in children, intussusception should be excluded before a prolonged course of non-operative management is pursued. US is the preferred modality for the diagnosis of intussusception with a high sensitivity and specificity avoiding radiation exposure. Ascites asses by US has a relatively high sensitivity for bowel strangulation. In children less than 1-2 years of age, an observation period of 24-48 hours may be considered for the stable infant with SBO. After that time the likehood of resolution is extremely low. Observation periods greater than 48 hours carry a higher risk of bowel ischemia and/or necrosis. Meta-analysis reveals that the incidence of complications is significant lower after laparoscopy surgery compared to laparotomy. Reason for conversion to open surgery include inadequate visualization due to bowel distension, multiple adhesions, and gangrenous bowel. Recently a large significant volume output on the 2nd day of conservative management greater than 11 ml/kg/24 hrs. can predict the eventual need of surgical intervention.

Congenital Solitary Kidney

The predominant cause of end-stage renal disease in children is congenital anomaly of the kidney and urinary tract. Due to fetal ultrasound patients with a solitary kidney are increasingly identified before birth. During fifth week of embryogenesis, the kidney is formed by the interaction and outgrowth between the ureteric bud of the mesonephric duct (from which renal pelvis, ureter and lower urinary tract originates), and the metanephric mesenchyme from where the renal parenchyma develops, including 900,000 nephrons per kidney to last a lifespan. Unilateral renal agenesis occurs with an approximate incidence of one in 2000 live births due to genetic and environmental factors. Failure of the ureteric bud to develop in utero results in unilateral renal agenesis. Males are affected more commonly and there is a left side kidney absence predominance solitary functioning kidney is a form of congenital anomaly of the kidney and includes a single kidney due to a contralateral multicystic dysplastic kidney (MCDK), or unilateral renal agenesis. In both cases the reduced kidney mass and nephron endowment predisposes children to chronic kidney injury. CSK is more likely to have associated syndromes or anomalies and have a worse outcome over time than MCDK. It has been recommended that CSK be classified as: agenesis (absence of one kidney found in utero 2nd trimester), aplasia (in-utero 2nd trimester rudimentary kidney with < 5% function on scan), MCDK, and undefined (found in third trimester or after birth and uncertain about the cause of the in-utero defect). A reduced functional nephron number results in compensatory glomerular hypertension and enlargement of remnant nephrons, indicating glomerular hyperfiltration. Children with a congenital solitary functioning kidney (CSK) have a reduced renal mass for a prolonged period of time being at risk of hyperfiltration injury. Prolonged increase in nephron and kidney size may lead to stretch-induced glomerular cell activation, fibrosis, vasoconstriction, and tubular cell nephrotoxicity. It is estimated that 50% of patients with CSK will develop hypertension, 32% chronic kidney injury, 20% proteinuria, 10% an impaired glomerular filtration rate (GFR) and 5% will die of renal failure during a lifetime. One-third of patients with CSK has signs of renal injury at a mean age of 10 years. Glomerular hyperfiltration injury is more common in the acquired solitary kidney than in the CSK due to the potential in utero for the congenital variety to form new nephrons. An impaired GFR is a relatively late phenomenon in children with a CSK because the first signs of renal injury generally include hypertension and (micro) albuminuria. Obesity in children with CSK is an additional factor for the development of chronic kidney disease. Clinical practice recommends that children with a CSK should be regularly evaluated for blood pressure, albuminuria/proteinuria, kidney function and size. Genetic counseling and analysis in children with an isolated and sporadic CSK are not recommended. Congenital functioning solitary kidneys with increased neonatal renal length as measured by US are born with an increased nephron number and with renal hyperplasia, rather than with early onset compensatory hypertrophy. Since nephrogenesis continues until about the 36th week of gestation, the hypertrophic growth in utero of CSK could be explained by renal hyperplasia with compensatory nephron formation. Likewise, failure of renal length growth in-utero identifies children with CSK without renal hyperplasia who carries a worse prognosis needing closer follow-up and surveillance. Specific independent risk factors responsible for long-term renal injury in children with CSK include a reduced renal length of the functioning kidney (insufficient hypertrophy), as well as recurrent urinary tract infections. The risk of developing proteinuria, hypertension, and/or worsened renal function for children with CSK as a result of MCDK or unilateral renal agenesis is low. Among the urologic abnormalities associated with CSK, vesicourethral reflux is the most common (10-20%). The standard to detect VUR in CSK is voiding cystourethrography which should be performed when US abnormalities of the CSK are found. The most frequently described extra-renal malformations involved with CSK include the heart, the gastrointestinal tract and the musculoskeletal and genital apparatus. Some extrarenal malformations associated with CSK include anomalies of the Mullerian system such as Herlyn-Werner-Wunderlich syndrome, also known as OHVIRA (obstructed hemivagina with ipsilateral renal agenesis), and Mayer-Rokitansky-KŸster-Hauser syndrome. Routine peri-menarche screening for Mullerian anomalies in girls with CSK may provide timely counseling, surgical treatment and prevention of associated complications such as endometriosis, infertility and miscarriages. All children born with CSK should be followed until adulthood.

Fibro-Adipose Vascular Anomaly

The term Fibro-adipose vascular (FAVA) anomaly has been given to a distinct entity that is characterized by fibrofatty infiltration of muscle, unusual phlebectasia with pain, and contracture of the affected extremity described in children. FAVA is extremely rare sporadic lesion, it often presents during young age, and occurs mostly in muscles of the lower extremity in 90% of the cases, followed by the upper extremity and trunk. The common presenting symptoms of FAVA are pain, functional restriction and swelling. Histologically FAVA is a complex mesenchymal malformation characterized by venous malformation surrounded by focal or diffuse fibro-adipose tissue within the skeletal muscle. Additional findings include lymphoplasmacytic aggregates, neural involvement by the anomaly, small foci of microcystic lymphatic malformations, cluster of thick-walled muscular channels, myxoid stroma, elastosis, and woven or lamellar pattern of the affected bone. All of FAVA lesions primarily involve muscle. The most common muscle involved include gastrocnemius and soleus, followed by the wrist. US usually shows heterogenous echogenic masses due to fibrofatty proliferation within the muscles and subcutaneous plane. MRI is diagnostic of FAVA. Three major types of MRI findings are found in FAVA: focal mass like lesions typically involving one anatomical region with well-defined margins, focal infiltrative lesions with ill-defined margins, and diffuse infiltrative lesions with ill-defined and no perceptible margins involving one or more anatomical region with dimensions that cannot be accurately measured. All FAVA lesions demonstrate heterogenous hyperintense T1 signal from the fat component and heterogenous enhancement. They also have intralesional and extrafascial anomalous dilated veins with characteristic beaded appearance of their wall. Flow within these venous channels is slow. Most patients are referred for a vascular (venous) malformation, with FAVA lesions often being misdiagnosed and labeled inaccurately. Misdiagnosis also included non-vascular entities such as muscle strain and soft-tissue tumor. Most patients are adolescent females which presents with chronic constant pain and functional impairment. The source of pain in FAVA is the fibrofatty tissue encircling nerves causing neuropathic pain commonly associated with muscle contracture. Recent study identified that somatic and mosaic gain-of-function mutations of the PIK3CA gene are found in FAVA, and FAVA belongs to the spectrum of PIK3CA-related overgrowth syndromes such as Klippel-Trenaunay syndrome and CLOVES (congenital lipomatous overgrowth, vascular malformation, epidermal nevi, and spinal/skeletal) anomalies. This gene mutation is the key lipid kinase that controls signaling pathways involved in cell proliferation, motility, survival, and metabolism. PIC3CA mutation excessively promotes activation of the mTOR (rapamycin) pathway. Sirolimus, a known mTOR inhibitor has an antiproliferative effect on various vascular anomalies including FAVA. FAVA has been managed by surgical excision, sclerotherapy and cryoablation. Traditionally, sclerotherapy was the first-line therapy for low-flow vascular malformations. FAVA differs from other venous malformations with its dominant solid fibrofatty component, which is less responsive to treatment with sclerotherapy. Current treatment includes percutaneous cryoablation for pain, sirolimus and surgical debulking and excision. Sclerotherapy is increasingly recognized to have little benefit for these patients owing to the presence of dominant fibrofatty component. Image-guided cryoablation is effective in decreasing pain in the symptomatic patient with FAVA due to a cytotoxic effect on the inflamed fibrofatty tissue. Surgical excision is favored in the focal lesion, indicated in patients with significant symptoms and signs who do not respond to conservative measures or cryoablation, or where these techniques are inappropriate. Sirolimus therapy have found to elicit a dramatic improvement in clinical symptoms. Patients achieve pain relief and tumor shrinkage within 4 and 5 weeks respectively of treatment. The duration of rapid tumor involution is seven months (6-12 months). For patients with partial response, surgical resection can be performed. No severe adverse effects of sirolimus were observed.    

PSU Volume 61 NO 04 OCTOBER 2023

Ventral Hernias

A ventral hernia is a hernia that occurs through the anterior abdominal wall muscles. Ventral hernias can be congenital or acquired. Congenital ventral hernias are the most common variety seen and include the epigastric and umbilical defects. Many umbilical defects undergo spontaneous resolution, otherwise they are usually repair with outpatient surgery after the age of two to four years. Acquired ventral hernias are usually those that developed after previous abdominal surgery described as incisional hernias, and ventral hernias that developed after conservative management of giant omphaloceles. Incisional hernias occurring through the site of a previous abdominal incision, are very rare in children and usually small-to-moderate in size. Incisional hernias are at risk of presenting with bowel incarceration and obstruction. Incisional hernias can be safely closed primarily. On the contrary, abdominal ventral hernias that develops after conservative management of a giant omphalocele are very large and difficult to manage. The nonoperative management of omphalocele, initial skin closure of gastroschisis and postoperative incisional hernias have been reported as the most common etiologies of ventral hernias in children. Repair of giant ventral hernias is very challenging. This is usually due to inadequate intraabdominal volume as a result of prolonged extra abdominal location of the viscera, which allowed the intraabdominal compartment to become hypoplastic. Reduction of the herniated viscera with tight fascial closure may result in intraabdominal compartment syndrome with a fatal outcome. Major problems associated with closure of large ventral hernia in such cases include angulation of the inferior vena cava which upon dissection and closure of the defect can cause circulatory failure and hematemesis, kinking of the suprahepatic vena cava with subsequent liver engorgement, adhesions of the liver to the skin and adhesions of the bowel to the abdominal wall causing bleeding from the liver or trauma to the bowel respectively. Routine MRI evaluation is recommended to delineate the abnormal anatomy accurately in order to prevent injury to the superficially lying venous structures during closure of the ventral hernia. The association of Beckwith-Wiedemann and Down's syndrome, Pentalogy of Cantrell and malrotation, as well as undiagnosed intracardiac anomaly contributed significantly to serious immediate postoperative morbidity during closure of these large ventral hernias. Several reconstructive methods of closure of large ventral hernias have been described, including stage silo closure, skin flaps closure, use of a prosthetic mesh (synthetic or biologic) bridge to span the fascial defect, use of tissue expansion, component separation, rotational flaps, and free flap coverage. Tissue expanders can be placed in a number of positions (intraperitoneal space, between fascial layers) to reclaim abdominal domain. The abdominal wall fascia can be bridge using a synthetic mesh. Gore-Tex has consistently proven favorable because is inter, intestine adhere minimally to it, and it maintains its strength while having the central portion excised serially over time. Component separation technique (CST) is another alternative in the closure of these large ventral hernias. The CST is an attractive surgical option for childrenÕs ventral hernias since it uses autologous tissue with minimal functional deficiencies as compared to rotational or free flap reconstructions. The benefit of the CST is that the release of muscle layers allows an expansion of the abdominal wall and closure of the midline fascia. CST can be augmented intraoperatively with a synthetic mesh or biologic prosthetic for added fascial bridging or reinforcing onlay or underlay. The mobilization of the skin and subcutaneous tissue necessary to perform this technique predispose the child to several complications including surgical site infection, skin necrosis, hematoma, and seroma. The need for multiple laparotomies carries the attendant risk of bowel injury, enterocutaneous fistula formation and prolonged hospital stay. The use of botulinum toxin and preoperative progressive pneumoperitoneum for repair of large ventral hernia is safe and applicable.

Esophageal Motility Disorders

The esophagus complex muscular tube utilizes coordinated peristalsis and relaxation of deglutition of the upper and lower esophageal sphincter to transport bolus from pharynx into the stomach. Disruption in peristalsis can lead to obstructive symptoms such as dysphagia, non-cardiac chest pain and regurgitation. Dysphagia to solid raise suspicion of a primary mechanical pathology, while dysphagia to liquids with or without dysphagia to solids is more suggestive of an esophageal motility disorder. Upper endoscopy is the first line diagnostic test for esophageal dysphagia. Primary esophageal motility disorders (EMD) encompass several clinical conditions of which achalasia is the most common in adults and children. Symptoms of EMD include dysphagia (most common), regurgitation, weight loss, and chest pain. High-resolution esophageal manometry is the best method to evaluate esophageal motility disorders in all ages. Motility disorders are classified as disorders of esophagogastric junction outflow (EGJ) and/or disorders of peristalsis. Disorders of EGJ outflow include achalasia and EGJ outflow obstruction. Motility disorders beyond achalasia include esophagogastric junction outflow obstruction, major disorders of peristalsis (distal esophageal spasm, hypercontractile esophagus, absent contractility), and minor disorders of peristalsis (ineffective esophageal motility, fragmented peristalsis). Definition of achalasia requires 100% absent peristalsis, defined as all swallows with either failed peristalsis or premature contraction and elevated integrated relaxation pressure above 15 mmHg of the lower esophageal sphincter (LES). Esophagogastric junction outflow obstruction disorders are characterized by an impaired lower esophageal sphincter relaxation with an integrated relaxation pressure (IRP) above 15 mmHg, and normal or weak peristalsis. Nearly 10% of patients undergoing manometry are identified as having EGJ outflow obstruction disorder. They may be caused by an anatomical abnormality at the cardia like hiatal hernia, disease of the esophageal wall, or be idiopathic with normal anatomy. To confirm an outflow obstruction a timed barium esophagogram should be performed. Management of this disorder is directed toward relief of the obstruction and ca performed with botulinum injection, pneumatic dilatation, laparoscopic Heller esophagomyotomy or peroral endoscopic myotomy. It is estimated that one-third of this cases present with spontaneous resolution of symptoms. Correction of the hiatal hernia is associated with excellent results. Distal esophageal spasm is defined by premature contractions with distal latency of less than 4.5 seconds in at least 20% of swallows with a normal IRP. This disorder can be managed with botulinum injection and peroral endoscopic myotomy. Hypercontractile esophagus (Jackhammer esophagus) is characterized by a distal contractile integral above 8000 mmHg/second/cm in at least 20% of swallows and normal distal latency. Symptomatic improvement of this motility disorder can be obtained using pharmacologic relaxation of the smooth muscle with phosphodiesterase-5 inhibitors or anticholinergic agents.  Absent contractility is characterized by aperistalsis in the setting of a normal LES relaxation with an IRP < 10 mmHg. This disorder is found in patients with connective tissue disorders and there is no specific treatment to restore or improve peristalsis. Ineffective esophageal motility (IEM) is defined by more than 70% ineffective swallows, at least 50% failed peristalsis with distal contractile integral less than 450 mmHg/second/cm and normal IRP. Is reported in as many as 30% of patients undergoing manometry with unclear clinical implications and management. IEM is the most common disorder in patients with dysphagia who have normal endoscopic findings, followed by achalasia and fragmented peristalsis. Ineffective esophageal motility has a higher prevalence in smooth muscle disorders such as scleroderma, other connective tissue disorders and gastroparesis. No effective treatment is available to restore impaired esophageal smooth muscle contractility. Ineffective esophageal motility impairs esophageal clearance and participates in the pathophysiology of gastroesophageal reflux disease. Delayed acid clearance from the esophagus in patients with a diagnosis of IEM is an important reason for the development of gastroesophageal reflux disease. Treatment is directed toward gastroesophageal reflux disease when dysmotility is secondary to this disease. Fragmented peristalsis is defined by more than 50% fragmented contractions with normal contraction vigor. It is unclear how to manage this disorder of motility.