PSU Volume 55 No 01 July 2020

Ovarian Immature Teratoma

Ovarian teratomas in children are the most common germ cell tumors. Can be mature, immature and malignant. The vast majority of ovarian teratoma are mature. Ovarian immature teratomas (OIT) represent 1% of ovarian tumors graded according to the proportion of tissue containing immature neural elements. More than 80% of immature teratoma has elevated levels of alpha-fetoprotein. Tumors with higher AFP levels exhibit additional foci of malignant germ cell components. Peak incidence occurs between 15 and 19 years of age presenting as pelvic mass, abnormal uterine bleeding, abdominal pain or abdominal distension. US shows a complex ovarian lesion (solid and cystic components) or a heterogenous lesion in CT-Scan. Fat and scattered calcifications can also be present. Staging represents findings at surgery whether the tumor is confined to the ovary, peritoneum, pelvis, lymph node, adjacent organs, bilateral or has malignant ascites. Grade refers to pathologic presence of immature tissue in lower power field. Immature teratomas behave in a malignant fashion only if foci of malignant germ cell elements (yolk sac tumor) are present or if they are resected incompletely giving rise to the growing teratoma syndrome. Grade at diagnosis is the most important risk factor for relapse across all age groups. In children with grade 1 and 2 tumors there are no relapse regardless of stage. The majority of relapses (20%) occur in children with grade 3 tumors. Grade 3 with stage I/II disease have excellent free survival in comparison with stage III/IV. Completeness of resection influences free survival. Most children with OIT will not need chemotherapy. Grade, stage and completeness of resection are important risk factors for relapse. Recurrent disease occurs within the pelvis at the site of the original tumor. Tumor size does not correlate with tumor grade. The management of ovarian immature teratoma is unilateral salpingo-oophorectomy plus comprehensive staging. Complete resection is a key factor in avoiding tumor relapse.  Routine biopsy of the unaffected ovary is unnecessary because immature teratoma is almost always unilateral. Lymphadenectomy does not provide any significant benefit to the survival of patients affected by immature teratoma. The reason to remove the tube with the tumor is to reduce an ectopic pregnancy risk. Initial adjuvant chemotherapy does not reduce future relapse or progression in OIT. Ovarian-sparing surgery during tumorectomy is an option being studied and depends on the anatomic feasibility of each case. Adjuvant chemotherapy is use for residual or recurrent disease though it may cause growing teratoma syndrome. Children with OIT should be follow-up with serial US and AFP levels.

Sinusoidal Obstruction Syndrome

Sinusoidal obstruction syndrome (SOS) is a hepatic veno-occlusive disease occurring as a frequent complication after high-dose chemotherapy in the setting of hematopoietic stem cell transplantation. It can also be seen after conventional chemotherapy in pediatric patients after receiving dactinomycin-based chemotherapy for Wilms tumor, rhabdomyosarcoma, medulloblastoma and malignant germ cell tumor. Intensive antileukemic regimens that use 6-thioguanine also predispose to hepatic SOS. The initiating event is injury to the endothelial cells at the sinusoidal surface of the hepatocyte by the chemotherapeutic agent. This causes obliteration of the hepatic venules as a result of subendothelial edema and microthrombosis leading to hepatic congestion, sinusoidal dilatation and portal hypertension with hepatocyte injury and death. A cascade of hypercoagulable and proinflammatory pathways causes further damage resulting in obstruction of hepatic venous outflow, portal hypertension and multi-organ failure. Diagnosis is clinical. This usually occurs in the third week after chemotherapy with symptoms such as fever, jaundice, tender hepatomegaly, vomiting, fluid retention, ascites, hypoalbuminemia, elevated serum transaminases, thrombocytopenia and prolonged PT and PTT. In children there is no limitation for time of onset of SOS and two or more of the symptoms described are diagnostic. Imaging could demonstrate signs of hepatic portal hypertension in late stages. The incidence of developing SOS in Wilms tumors receiving chemotherapy is 1.5 to 8%. Liver SOS appears after the 2nd to 6th dose of Dactinomycin, seven to 14 days after the last dose. Special vulnerability occurs in children less than one year of age, right sided Wilms tumor and those receiving abdominal radiotherapy. Management of hepatic SOS is supportive with antibiotics, fluid restriction, diuretics, plasma, albumin and platelets transfusions. Pharmacologic intervention includes anticoagulants such as defibrotide, antithrombin III, heparin, protein C concentrate, N-acetylcysteine and gabexate mesylate. High dose methylprednisolone and aspirin has been utilized in other patients. Most children recover after approximately ten days of medical management.  

Hepatic Hemangioendothelioma Revisited

Infantile hepatic hemangioendothelioma (IHH) is a very rare, benign vascular tumor that appears during the first six-months of life with the potential to regress spontaneously. Considered the most common vascular tumor of the liver in children is associated with a high mortality rate. IHH can be focal, multifocal or diffuse in the liver. Focal IHH are fully grown tumors at birth that rapidly involutes with time. Multifocal IHH are individual lesions separated by normal liver parenchyma. Diffuse IHH is characterized by extensive replacement of hepatic parenchyma with multiple lesions. IHH can be associated with high output congestive heart failure, anemia, hypothyroidism, consumption coagulopathy, thrombocytopenia (Kasabach-Merritt syndrome), hepatomegaly (causing abdominal compartment syndrome),  and cutaneous hemangiomas. Prenatal diagnosis has been associated with hydrops fetalis. Postnatal diagnosis is established with US, CT-Scan and MRI. More than five cutaneous hemangiomas lesions are indication for liver US in search of IHH. Alpha-fetoprotein levels should be obtained to differentiate from hepatoblastoma. IHH can be associated with consumptive hypothyroidism due to overproduction of type 3 iodothyronine deiodinase which deactivates thyroid hormones. Mortality results from high-output cardiac failure secondary to arteriovenous shunting within the tumor (up to 50% of the cardiac output can be diverted), respiratory compromise, hepatic failure, intraperitoneal hemorrhage and consumptive coagulopathy. The arteriovenous shunting can result in a decreased of systemic blood volume and increase of pulmonary blood volume thus the cardiac output increase. The younger the age at diagnosis, the more severe the cardiac symptoms. Natural history of asymptomatic IHH is spontaneous involution. Symptomatic lesions need aggressive management. Radiotherapy and chemotherapy have not shown consistently good results. Steroid and alpha-interferon are used as initial treatment to inhibit proliferation of endothelial cells with mixed results. Propranolol, a beta blocker, is now the preferred systemic therapy for problematic IHH due to promotion of pericyte-mediated vasoconstriction, and decrease and cease of growth with more rapid involution of the lesion. Severe bilobar disease might need percutaneous hepatic artery embolization or transplantation. Early embolization is recommended for children with focal or multifocal lesions presenting as shunts or those unresponsive to medication. Hepatic artery ligation or embolization should not be done in patients with shunting from the portal vein to the hepatic vein and minimal systemic arterial collateral circulation since it might result in hepatic necrosis.

PSU Volume 55 No 02 AUGUST 2020

Thoracoscopic Repair Diaphragmatic Eventration

Diaphragmatic eventration occurs due to a congenital structural defect in the diaphragm or after injury to the phrenic nerve. Phrenic nerve in jury occurs due to traction on the nerve during birth or directly after an open cardiac procedure in the child. When the child develops diaphragmatic eventration, he can develop mild gastrointestinal symptoms up to life-threatening respiratory distress requiring mechanical ventilatory support. In infants, the diaphragmatic eventration causes progressive dyspnea on exertion or respiratory infection. When the child develops symptoms (dyspnea, shortness of breath, labored respiration, chest retraction) or need of mechanical ventilation plication repair of the diaphragm is  needed. Diaphragmatic plication is usually performed using a standard posterolateral open thoracotomy through the 5th or 6th intercostal space. During the past years thoracoscopy has been utilized to accomplish plication of the diaphragm. The technique uses general anesthesia with single lung ventilation most commonly. Three to four trocars are placed depending on the need to reduce the elevated diaphragm. Carbon dioxide is insufflated in low pressure levels (4-6 mm Hg) to reduce the risk of developing hypercapnia, hemodynamic instability, acidosis and hypoxia. The single lung ventilation can be accomplished using a Fogarty catheter to block the main bronchus ipsilateral to the side of the eventration. Plication is the accomplished posterolateral to anteromedial with interrupted nonabsorbable sutures to avoid phrenic nerve injury and suture breakdown respectively. A chest tube drainage is utilized for a short period of time until the pneumothorax is evacuated. Thoracoscopy offers the advantage of smaller wounds, better cosmetic results, faster recovery, less thoracic pain, less incidence of late thoracotomy sequela (scoliosis), immediate pulmonary function improvement with less impaired ventilatory function postoperatively. Plication can be performed using a double purse-string technique. Plicating the diaphragm using a thoracoscopic approach is feasible, safe, easy to perform and efficient. Early thoracoscopic plication is a good treatment option for pediatric patients with symptomatic diaphragmatic eventration after surgery for congenital heart disease.   

Intestinal Pseudo-obstruction

Pediatric intestinal pseudo-obstruction (PIPO) is a rare disorder characterized by the chronic inability of the bowel to propel its content in the absence of any mechanical lesion occluding the gut. Diagnosis of PIPO needs at least two parameters: objective measure of small intestinal neuromuscular involvement (manometry, histopathology, transit), recurrent or persistently dilated bowel loops, associated genetic or metabolic abnormalities, and inability to maintain nutrition or growth with oral feedings. PIPO patients develop bile vomiting, failure to pass gas and stool, and progressive abdominal distension. PIPO could be associated with bladder dysmotility or after a Ladd's procedure for malrotation. Hirschsprung's disease and hypothyroidism should be excluded.  Megacystis is a prenatal sign of PIPO. Most cases present signs within the first month of life. Immaturity of the intestinal motility in premature infants can mimic PIPO. Late-onset or infant PIPO presents with recurrent and intermittent episodes of gastric, intestinal or colonic obstruction and is triggered by infections, fever, general anesthesia or emotional stress. Associated abdominal pain could lead to feeding difficulties and malnutrition. Megacystis with hypocontractile detrusor, increase bladder capacity and compliance occurs in more than 50% of PIPO cases. This usually associated with uretero-hydronephrosis and minimal vesico-ureteral reflux. Abdominal films shows bowel dilatation with air-fluid levels. Entero CT-Scan, MRI and/or small bowel follow-through studies using water soluble contrast is needed to exclude mechanical obstruction. The most accurate and sensitive measure of GI transit is obtained with nuclear studies such as gastric emptying scans. Antroduodenal manometry studies are indicated for diagnosis and classification of the pseudo-obstruction present. Esophageal, colonic and anorectal manometry is used to determine extend of disease. Unnecessary surgery should be avoided as these patients develop dense adhesions. Should surgery be performed full-thickness biopsy of the affected bowel for nerve, muscle and interticial cell of Cajal should be performed. Laparoscopic biopsy are indicated for diagnostic purpose obtaining a minimum tissue specimen of 0.5 x 0.5 cm. Full work-up include labs tests, genetic testing, endoscopy, neurologic evaluation and imaging. Nutrition should be optimized. Drug therapy aims to promote GI motility, limit intestinal inflammation and suppress bacterial overgrowth. Erythromycin, pyridostigmine and octreotide are effective drug therapy in some children. Venting or feeding gastrostomy and/or jejunostomy should be considered in patients with PIPO, and decompressive ileostomy in those on parenteral nutrition. Bowel resection should be avoided to avoid short bowel syndrome or liver failure. Definitive cure is bowel transplantation. Stomal prolapse, recurrent pancreatitis, diversion colitis, and electrolytes imbalance are the most common complications.            

Diffuse Hyperplastic Perilobar Nephroblastomatosis

Nephroblastomatosis refers to a premalignant condition associated with Wilms tumor characterized by multiple residual embryonal cells known as nephrogenic rests. It is considered an intermediate preneoplastic stage in the sequence of Wilms tumorigenesis. Nephrogenic rests are clusters of embryonic metanephric that can be found incidentally in less than 1% of infants. They can be single or multiple, focal or diffuse lesions identified in the renal parenchyma. Universal (panlobar) nephroblastomatosis denotes complete replacement of the renal lobe by nephrogenic tissue. The fate of nephrogenic rests and nephroblastomatosis varies and includes obsolescence, sclerosis, dormancy, hyperplasia, or neoplasia. Evidence strongly suggests that neoplastic transformation of nephrogenic rests results in Wilms' tumor (nephroblastoma). Depending on where in the renal parenchyma they are located they are either classified as perilobar or intralobar. Perilobar rests show a strong association with synchronous bilateral Wilms' tumors, whereas intralobar rests are more strongly associated with metachronous tumors.  Perilobar nephrogenic rests are found in the renal peripheral cortex associated with fetal overgrowth disorders. Intralobar rests occur as focal lesion inside the central renal parenchyma. Diffuse hyperplastic perilobar nephroblastomatosis (DHPLNB) is associated with an increase risk of developing into a malignant nephroblastoma. DHPLNB can be seen in US or CT Scan as enlarged diffusely hypoechogenic kidneys or enhancing peripheral nodularity with scattered patches of adjacent normal renal parenchyma respectively. MRI demonstrates peripheral nodules with low signal intensity on T1 and T2 images. When DHPLNB is associated with Wilms tumor management is multimodal including surgery, chemotherapy and radiotherapy. Poor prognostic factors include an anaplastic tumor, high stage, unfavorable molecular and genetic marker and age greater than two years of age. The diagnosis of a Wilms tumor should be favored over a nephrogenic rest when a renal mass is spherical, exophytic, or larger than 1.75 cm. Most DHPLNB cases occur with bilateral renal involvement and as such management strategies should consider nephron-sparing procedures to avoid leaving the child anephric hence renal insufficiency, dialysis dependent and in need for renal transplantation. In such cases 18 weeks of vincristine and actinomycin D should be used as chemotherapy for an extended period until nephrogenic rest disappear. In case of bilateral DHPLNB laparoscopic nephro-sparing resection can be performed so long as the capsule of the nephrogenic rest stays intact and there is no spillage of the lesion.

PSU Volume 55 NO 03 SEPTEMBER 2020

Genital Warts

Genital warts in children are rare and usually (>90%) the result of infestation of the keratinocytes with human papilloma virus (HPV) in the form of condyloma acuminatum (CA). This includes warts in the genital region of prepubertal infant or child such as perianal, vestibular, vulvar or periurethral. Main clinical manifestations of anal warts are cauliflower-like condylomata acuminata that usually involves moist surfaces, keratotic and smooth papular warts usually on dry surfaces, and subclinical flat warts that can be found on any mucosal or cutaneous surface. Mode of transmission can occur from an infected maternal birth canal (perinatally), by autoinoculation or heteroinoculation from common hand warts, through sexual abuse and possibly indirect transmission via fomites. Girls are twice as often affected as boys. Predisposing factors for genital warts include social problems, lack of hygiene, promiscuity, diabetes, HIV infected individuals and ammoniacal erythema. Presence of genital warts in children raises concern of possible sexual abuse. The probability of sexual abuse increases with the age f the child. CA in children is a diagnostic difficulty due to the possibility of sexual transmission, though non-sexual transmission is very frequent also in children. Nonsexual CA is present almost exclusively in the mucosal epithelium in children. There is a need for a multidisciplinary approach to management with potential social-medicolegal implications. Conventional management for genital warts in children relies on chemical (podophyllotoxin) and physical destruction methods that can be difficult, painful and variably effective with a high recurrent rate, frequently requiring general anesthesia. Intraurethral fluorouracil and lidocaine instillation is effective in CA. Other modality of management includes immunotherapy such as topical Imiquimod cream, cimetidine, and intralesional or systemic interferon. Surgical excision of genital warts is safe, effective and provides opportunity to assess the extent of the lesion and tissue for accurate diagnosis. Indications for surgical management include large, recurrent or refractory lesions, as well as the need for histological identification and acquiring tissue for immunotherapy if needed. The technique of ultrasonic surgical aspiration for the management of CA under general anesthesia results in minimal discomfort, rapid healing and no scarring. Electrocautery fulguration and cryosurgery have also been found successful therapy options. The primary prevention of HPV infection through vaccination is  essential in decreasing the incidence of the disease.

Postappendectomy Intraabdominal Abscess

Intraabdominal abscess (IA) formation is a common secondary complication after surgery for  perforated appendicitis with an incidence as high as 20%. The technique in removing the perforated appendix whether laparoscopic or open does not have an impact in the development of an IA. The child with a postappendectomy fluid collection can develop prolonged fever, leukocytosis, elevated CPR, abdominal pain, diarrhea, and tachycardia. The initial imaging of choice when looking for a fluid collection is an ultrasound since carries no radiation injury risk to the child. Should the child not respond to further antibiotic therapy or signs of sepsis ensues the next imaging should be an abdominopelvic CT-Scan with oral/IV contrast looking for enhancement from the collection and anatomic window for drainage. Lymphopenia, due to suppression of immune function after sepsis, is a predictive indicator of an IA and can be considered to decide duration of antibiotic therapy. The same occurs with the use of the neutrophil to lymphocyte ratio above 8. They are complimentary. Management of postappendectomy IA includes intravenous antibiotics, percutaneous interventional radiology (IR) drainage or open/laparoscopic drainage. The size of the fluid collection is decisive since collections measuring less than 3 to 5 cm can be managed solely with antibiotics. Collections larger than 5 cm (or 100 cc volume) need percutaneous IR drainage, claimed as treatment of choice for these larger collections with a high success rate and low morbidity. Main contraindication to IR drainage includes lack of access such as interloop abscess or proximity to vascular or other solid organs. Complex or thick abscess drained can benefit from using fibrinolytic therapy with tissue  plasma activator if drain is clogged. Complications of IR drainage include enterotomy with fistula formation, hemorrhage and sepsis. Should IR drainage not be amenable, surgical drainage using either an open or laparoscopic technique might be needed. Open laparotomy has inherent risks such as incisional pain, high wound infection rate, incisional hernias and poor cosmetic results. The final issue is how long to give IV antibiotics after drainage of a postappendectomy IA. Three to five days is sufficient antibiotic therapy should the child normalize GI tract function, has no abdominal symptom, normalize WBC count < 11000, normal lymphocyte count, normal CRP, no tachycardia, no tachypnea and afebrile. There is no need to repeat imaging studies in patients that have recovered physically and laboratory from a drained intraabdominal abscess postappendectomy. Prolonged use of antibiotics after surgery for perforated appendicitis does not reduce the incidence of postoperative abscess formation.  

Empyema: Fibrinolytics vs VATS

Empyema is an infection of the pleural cavity most commonly caused by an initial postpneumonic infected fluid collection. Less than 1% of childhood pneumonias are complicated by pleural empyemas. Empyema goes through three stages: Stage I (exudative) - effusion, pH > 7.2, LDH < 1000 IU/L, glucose < 60 mg%, negative culture, no loculation; Stage II (fibrinopurulent) - increase loculation, positive culture/gram stain, suppuration with fibrin deposit, > 10K WBC (empyema); Stage III (organized) - multiloculated parapneumonic effusion, trapped lung, lung restriction and pleural cortex formation. Stage I is simple, while Stage II and III is complicated empyema. Initial management of postpneumonic fluid collection is intravenous antibiotics. If there is no clinical response or fluid collection persists/enlarged after 48 hrs of therapy, imaged-guided chest tube drainage should be performed. Definitive management of empyema involves cleaning the pleural space of pus and solid material with video assisted thoracoscopic debridement (VATS) or chemical dissolution with fibrinolytic therapy. VATS has shown to produce earlier and more complete resolution of empyema than chest tube drainage. With VATS the majority of patients experience complete recovery with decreased chest tube duration, duration of antibiotics, need for repeat procedures, length of stay in hospital and mortality. Fibrinolytics (streptokinase, urokinase, recombinant tPA) break down fibrin, the dominant component of the extracellular matrix of septations and solid debris identified in empyemas. Fibrinolysis has been to be superior to chest tube drainage alone. Chest tube placement with fibrinolytic instillation done under conscious sedation results in similar success rate to VATS with marked reduction in costs. An algorithm that begins with fibrinolytics and progress to VATS as needed is superior in resource conservation without loss of efficacy. Best available evidence suggests that although primary VATS and fibrinolysis are clinically equivalent, fibrinolysis is less expensive, less invasive and can be performed under conscious sedation rather than using general anesthesia. Fibrinolysis has the added advantage of earlier pleural drainage and shorter length of stay postprocedure compared with VATS. Less than 4 to 20% of patients managed with primary fibrinolysis will require operative intervention. A repeated course of fibrinolytic therapy after tube repositioning can lead to successful nonoperative management of empyema without increasing hospital stay. Secondary surgical procedures are not significantly less frequent after initial intrapleural fibrinolytic therapy than after initial pleural puncture or pleural draining catheter. VATS treatment at any time during the disease is not associated with shorter length of stay. VATS is associated with a significant reduction in the thoracotomy rate, historically. Primary VATS is associated with less chest radiation exposure, shorter duration of mechanical ventilation and fewer days admitted in intensive and hospital than chest tube fibrinolysis. We still need to identify risk factor for fibrinolytic therapy failure.                 

PSU Volume 55 NO 04 OCTOBER 2020

Sirolimus for Lymphatic Malformations

Vascular malformations consist of congenital anomalies that can involve four types of vessels (capillary, lymphatic, venous and arterial). They are further subdivided in low- or high-flow vascular malformation. Lymphatic malformations are rare low-flow congenital vascular malformation occurring due to abnormal embryologic development of lymphatic vessels classified as macrocystic, microcystic or combined. Treatment frequently includes surgical excision and debridement, laser, sclerotherapy and embolization. Growth and expansion of vascular/lymphatic malformations cause disfigurement, chronic pain, recurrent infections, coagulopathies, organ dysfunction and death. Sirolimus, also known as rapamycin, is an mTOR inhibitor. mTOR is a serine/threonine kinase that acts as a master switch in cell proliferation, apoptosis, metabolism and angio/lymphangiogenesis. Sirolimus inhibit directly the mTOR pathway which inhibits cell proliferation, angiogenesis and lymphangiogenesis. It is used to prevent rejection of kidney transplants. The overall success rate of sirolimus in vascular and lymphatic malformation is 80%, presenting as improvement in radiologic imaging and reduction in symptoms at a median time of 10 weeks, with a reported nonspecific decrease in lesion size. In hepatic hemangioendothelioma with life-threatening Kasabach-Merritt syndrome, sirolimus is associated with resolution of coagulopathy in 93% of patients in two weeks period. In lymphatic anomalies oral sirolimus is associated with clinical benefit in 95% of patients with decrease of lesion size. Clinical improvement is observed in 75% of patients after three weeks of therapy. Dose most often prescribed is 0.8 mg/square meters twice daily in the pediatric patient. The more favorable response to sirolimus is seen in young patients less than two years old suggesting therapy should be started early in life. Mainly low-flow lesions, overgrowth syndromes with low-flow components and vascular anomalies that demonstrate upregulation of the mTOR pathway respond to sirolimus in most cases probably due to inhibition of lymphatic expansion and soft-tissue overgrowth. Topical use of sirolimus in cases of skin malformations with lymphatic components such as congenital lymphatic-venous malformations is both efficient and safe. Side effects of oral sirolimus include oral mucositis, fatigue, headaches, hypertension, thrombocytopenia, leucopenia, anemia, hyperlipidemia, hyperglycemia, hypokalemia, increase liver enzymes and rash. Side effects after sirolimus therapy are manageable, with no effect in future growth and development.

Thoracoscopic Repair of CDH

Congenital diaphragmatic hernia (CDH) is a defect caused by incomplete closure of the fetal posterolateral diaphragm muscle during embryonic development with entry of abdominal organs into the thoracic cavity resulting in lung hypoplasia. The defect is easy to repair with primary closure or patch replacement through a transabdominal subcostal incision or thoracotomy. The former is preferred in order to rearrange the hernia content into the abdomen. Patch repair has a significant higher recurrence rate than primary closure. The prognosis of CDH is primarily determined by the degree of persistent pulmonary hypertension and pulmonary hypoplasia. Surgical readiness for CDH repair implies that urine output is > 1 ml/kg/hr, lactate is < 3 mmol/L, FiO2 < 0.5, normal blood pressure and pulmonary pressure less than systemic pressure. Minimally invasive techniques using both laparoscopy or thoracoscopy have recently been implemented for repair of CDH. Advantages of the thoracoscopic approach include less pain, less incisional complications along with a reduction in surgical stress. Some surgeons are reluctant to do a thoracoscopic approach as malrotation cannot be managed adequately, though the incidence of acute volvulus is very low. Contraindications for thoracoscopy in CDH include babies using ECMO therapy. Thoracoscopy is not contraindicated in newborns as a relative hypercapnia can be tolerated without adverse effect in terms of neurological development. With low insufflation pressures (4-7 mmHg), CDH patients have significant improved hypercapnia and acidosis. Large defects and defects unable to reduce the herniated intrathoracic abdominal organs are reason for conversion. Use of patches to close larger diaphragmatic defects is instigated by the high percentage of recurrence (33%) in the thoracoscopic primary repair group. The liberal use of patches to reconstruct the dome of the diaphragm has reduced the incidence of recurrence to 12%. The recurrence rate is higher for thoracoscopy repair than primary repair. Factors associated with recurrence included the nature of the defect (large, right, absence of peripheral rim), associated conditions (severe pulmonary hypertension) and the surgical approach (use of patch, minimally invasive approach). The surgical postoperative mortality between the open and thoracoscopic approach favors the later, but is non-concluding since patients with less severe disease or with late presentation that have better survival (less lung hypoplasia) are better candidates for the minimal invasive approach. Also patch repair is associated with higher mortality given these patients are more likely in ECMO, presents with liver herniation and absent peripheral rim. Use of biologic mesh underlay appears to confer a reduced hernia recurrence.

Intraoperative Temperature and SSI

Perioperative temperature regulation during surgery in children can be a determinant of several factors including surgical site infections (SSI). Surgical site infections are the third leading cause of nosocomial infections among surgical patients. SSI is a major cause of postoperative morbidity also associated with increase risk of mortality. SSI increases surgical stay and hospital costs. Measures to prevent SSI includes use of prophylactic preoperative antibiotics, use of hair clippers, appropriate surgical field preparation and avoidance of postoperative hyperglycemia. Intraoperative hypothermia defined as core temperature < 36.0 C during surgery is a common complication among surgical patients. Hypothermia triggers thermo-regulatory vasoconstriction, moving the Bohr curve toward the left and decreasing the partial pressure of oxygen in tissues, leading to local acidosis. It also impairs oxidative killing by neutrophils, interferes with collagen deposition resulting in impaired wound healing. Infants are more susceptible to temperature instability owing to their immature thermoregulatory systems and increased exposed surface to volume ratio. Hyperthermia is defined as a temperature above 38 grade C. SSI has not been demonstrated to increase with intraoperative and/or immediate postoperative hypothermia in children. On the other side, hyperthermia at any point during the case or immediately postoperatively is associated with higher odds of developing SSI within 30 days of surgery. Babies undergoing laparotomy for necrotizing enterocolitis who have a precipitous drop in intraoperative temperature have no increased in SSI development. In fact controlled hypothermia in NEC cases may be advantageous similar to its use in hypoxic ischemic encephalopathy, severe liver failure and other conditions. Hypothermia indices a regulation of immune response with decrease oxidative stress and decrease leukocyte accumulation that help to explain this ‘protective' effect. On the other side, hypothermia causes deleterious effects such as coagulation disturbances, hypotension and unreliable action of anesthetic agents with more respiratory, thermoregulatory and cardiovascular intervention needed for stabilization. Risk factor for hypothermia in surgical patients include colder ambient temperature and longer case length. Blood transfusions given preop, intraoperatively and within 72 hours of surgery are associated with development of SSI. After reviewing several series, intraoperative hypothermia is not significantly associated with SSI.     

PSU Volume 55 No 05 NOVEMBER 2020

Boerhaave's Syndrome

Spontaneous rupture of the esophagus after a sudden increase in intraluminal pressure is known as Boerhaave's syndrome. The sudden increase in intraluminal pressure is most commonly caused by vomiting, but other causes of barogenic rupture include coughing, childbirth, defecation, seizures and blunt abdominal trauma. Spontaneous transmural esophageal rupture can also be seen as a primary manifestation of eosinophilic esophagitis preceded by an episode of food impaction with induced vomiting. In adults, the esophageal rupture is usually longitudinal, from 2 to 6 cm long, involves the distal thoracic esophagus usually toward the left into the left pleura. Rupture of the cervical, middle third or abdominal segment of the esophagus is rare. In most children the rupture in the distal esophagus is on the right side into the right pleural cavity. Sudden chest pain after the exerting pressure is the most common symptom. Half cases have the triad of forceful vomiting, mild hematemesis and substernal chest pain. With esophageal rupture and mediastinitis the child develops tachycardia, diaphoresis, fever and hypotension. Simple chest films reveals effusion, pneumothorax, hydropneumothorax, and subcutaneous emphysema. The diagnosis of Boerhaave's syndrome is confirmed with a simple water-soluble oral contrast study of the esophagus or CT-Scan of the chest. The esophageal tear may be diagnosed with esophagoscopy, but insufflation with high pressure may worsen pneumothorax or pneumomediastinum and cause life-threatening tension pneumothorax. Delaying the diagnosis of Boerhaave's syndrome increases the mortality due to mediastinitis. Initial management consist of antibiotics and chest tube drainage until the diagnosis is confirmed. Conservative management may be applied to children with small defects, contamination limited to the mediastinum and late diagnosis (> 24 hours after symptoms). Most patient will need an operation as treatment of choice which may consist of primary closure of the perforation, partial resection of the esophagus, drainage, or intraluminal stent. Primary closure can be covered with a pleural patch or fundoplication over the defect.      

Laparoscopic Excision Urachal Remnant

Urachal remnants are rare congenital anomalies pertaining to the development and involution of the urachus. The urachus is the embryological remnant of the allantois. A vestigial fibrous cord forms that obliterates in normal development to form a cord lying between the peritoneum and transversalis fascia and connecting the umbilicus to the bladder dome. Failure of obliteration at birth in the connection of the bladder to the umbilicus results in a urachal anomaly. Five urachal remnants are recognized and they  include: patent urachus with urine coming from the umbilicus (fistula), vesicourachal diverticulum, urachal sinus, urachal cyst and alternating fistula which drain either to the umbilicus or bladder. Urachal cyst is the most common anomaly of the urachus occurring in approximately one of 5000 births. Though clinically asymptomatic, the child can present with abdominal suprapubic pain, infraumbilical swelling with erythema, urinary symptoms (dysuria), infection of the cyst, umbilical drainage, umbilical mass, omphalitis and incidental finding during surgery. Persistent urachal anomalies can lead to recurring infection, stone formation and development of adenocarcinoma in the epithelium of the urachus. Urachal anomalies are associated with vesicoureteral reflux, hypospadia, meatal stenosis and ureteropelvic obstruction. Infection is the most common complication of urachal remnants. When infected it might need percutaneous drainage and systemic antibiotics followed by excision. Diagnosis can be established with ultrasound, CT-Scan, MRI or VCUG (less sensitivity; not part of standard evaluation). Managements of urachal anomalies include resection of the urachus throughout its entire length from the navel to include a cuff of normal bladder to avoid leaving urachal epithelium behind. There is controversy whether to do bladder cuff excision to all cases. In patent urachus and diverticulum remnant bladder cuff resection is indicated. Without bladder cuff excision postoperative Foley time, recurrence and complications are significantly less. Traditionally this urachal resection has been performed using an open hypogastric transverse or midline vertical incision. During the past 20 years the laparoscopic technique has been utilized to manage urachal anomalies in children and adults. Three trocar technique is usually utilized. The bladder cuff resection can be performed with double endoloops sutures as using a mechanical stapler machine can bring problems of future stone formation within the suture line or bleeding from the staplers. The laparoscopic approach confirms the presence of the urachus, enables magnified dissection along the extraperineal plane until the dome of the bladder in the space of Retzius. The laparoscopic approach is associated with minimal postoperative pain, rapid recovery and return to normal activities with the added advantage of better cosmetic results.       

Angiosarcoma

Angiosarcomas are extremely rare malignant vascular tumors originating from endothelial cells differentiation found almost anywhere in the body. They account for less than 1%of all sarcomas in children. Angiosarcomas predominantly arise from skin and subcutaneous tissue of the head and neck region, but they may also arise from deep soft tissue and other organs such as liver, spleen, kidney, heart, breast, thyroid gland and bone. They are associated with chronic lymphedema, radiation, arteriovenous fistulas and chronically immunosuppressed patients. Some authors have described angiosarcoma in children developing as a result of exposure to environmental factors such as radiation or arsenic. Histologically angiosarcomas can be well-differentiated to high-grade, stroma poor epithelioid neoplasms categorized as papillary, spindled, epithelioid or plasmacytoid. More than 50% of angiosarcomas demonstrated epithelioid characteristics. Epithelioid angiosarcomas tumor cells often forms sheets tubules or cluster of epithelioid malignant cells. In the liver, angiosarcoma presents as an abdominal mass. Associated symptoms can be jaundice, abdominal pain, vomiting, fever, tachypnea, dyspnea and anemia. High output cardiac failure, ascites, disseminated intravascular coagulation, bleeding and Kasabach-Merritt syndrome has also been reported in hepatic angiosarcoma in children. Diagnosis is made with US, CT-Scan and MRI. Adequate representative tissue is needed to establish a histologic diagnosis usually obtained through laparotomy. Overall prognosis of hepatic angiosarcoma is very poor regardless of therapy. Combination of chemotherapy, radiotherapy and surgical resection seldom provides a long-term disease free survival in children. Liver transplantation also carries a high recurrence rate and poor posttransplant survival. Splenic angiosarcoma is extremely rare, aggressive malignancy that is also uniformly fatal. Only children with localized disease amenable to surgical resection can achieve long-term survival. They present with abdominal pain, pancytopenia and splenomegaly. Splenic angiosarcomas proliferate rapidly, recur locally, spread widely and have a propensity to lymph node dissemination. Small tumor size (< 5 cm) is associated with better prognosis. Overall prognosis is grim.

PSU Volume 55 NO 06 DECEMBER 2020

Leydig Cell Tumor

Testicular sex-cord-stromal tumors are very rare in children developing from nongerminative tissue with different clinical and biologic behavior. They account for 8% of all testicular neoplasm in children occurring within months of birth or during puberty. The main histological types include Leydig cell tumor, Sertoli cell tumors, juvenile granulosa cell tumor and undifferentiated cell tumor.  Leydig cell tumor (LCT) is the most common testicular sex cord-stromal tumor, appears between five and 10 years of age (prepubertal), is benign in most children (90%), and bilateral in 10% of cases. Leydig cells are normally present as single cells or small clusters in the interstitium between the seminiferous tubules. They are involved in development of secondary male characteristics and maintenance of spermatogenesis as they produce testosterone when stimulated by LH. Hormonal activity is observed in 20% of LCT cases characterized by symptoms of precocious pseudopuberty due to androgenic hormone production along with gynecomastia in a few cases. LCT is a steroid secreting tumor mainly producing androgens (testosterone, androstenedione, dehydroepiandrosterone, 17 alpha-hydroxyprogesterone), but they can produce estrogens. Precocious puberty is the primary presenting feature of LCT including pubic hair, penile growth, scrotal hyper pigmentation, changes in body odor and advanced bone age. Children may have unilateral or bilateral testicular enlargement or a painless palpable mass in the testis. Scrotal ultrasound may reveal an avascular, hyperechoic discrete lesion. This can be followed with an MRI to avoid irradiating the scrotum. Children with suspected LCT should undergo measurement of alpha-fetoprotein, HCG, testosterone, FSH, LH and prolactin. The definite diagnosis is established by excisional biopsy. This is approach through an inguinal incision delivering the testis and cord into the wound area. The spermatic cord should be atraumatically occluded during dissection and removal of the tumor from the testis parenchyma (enucleation). Frozen-section can clarify the benign nature of the tumor, intraoperative ultrasound that surgical borders are tumor-free, hence vascular occlusion is terminated and orchiopexy is performed. Positive surgical margins after enucleation can be managed with observation and hormone determination obviating completion orchiectomy. Large size tumors (> 5 cm), infiltrative margins, areas of hemorrhage and necrosis extending beyond the testicular parenchyma, nuclear atypia, high mitotic count and angiolymphatic invasion suggest the very rare malignant variant of LCT. For malignant LCT inguinal orchiectomy with retroperitoneal lymphadenectomy is required as metastasis commonly involve retroperitoneal nodes and survival is reduced to three years after surgery. Chemotherapy has limited efficacy in malignant LCT, while there is no role for radiotherapy. Signs of precocious pseudopuberty or gynecomastia regress following tumor removal. Leydig cell hyperplasia, though very rare, presents identical to LCT and is managed with the same protocol. Central precocious puberty arises from the rebound secretion of LH after surgical removal of LCT and long-term endocrinology evaluation is warranted.

Persistent Cloaca: Newborn management

When a female child is born with a single perineal orifice usually located where the urethra is normally seen the diagnosis is persistent cloaca. The bladder, vagina and rectum are connected to this single perineal channel. Cloaca represents a spectrum of defects. Two-third has a common channel less than 3 cm with a low incidence of associated malformations, while one-third have common channels larger than 3 cm with a higher incidence of defects. During the first 24 hours of life the neonate would receive intravenous fluids, antibiotics and nasogastric decompression and be evaluated for associated defects including cardiac malformations, esophageal atresia and renal anomalies. A totally diverting descending colostomy should be constructed early in life to avoid urogenital infections.  Before the colostomy construction a child with cloaca must undergo the following studies: Simple abdominal films looking for duodenal atresia or vertebral anomalies, Abdominal and pelvic US in search of kidney anomalies (hydronephrosis) or hydrocolpus, echocardiogram for cardiac anomalies, spinal ultrasound and x-rays for tethered cord syndrome and sacral anomalies. Missed tethered cord have a negative implication for bowel, bladder and ambulatory function. Hydrocolpus occur in over one-third of children with cloaca. Hydrocolpus compress the bladder trigone causing uretero-pelvic obstruction, bilateral megaureters and hydronephrosis. It can also cause pyocolpos. In either case the hydrocolpus should be drained concomitantly when performing the colostomy. This includes draining two hemi-vaginas if present through a window created in the septal wall. A pigtail catheter or Foley can be use. Before performing the main repair of the cloaca the child should undergo radiological studies such as distal colostogram, common channel sinogram, MRI of the pelvis, along with endoscopic evaluation of the common channel to determine the distance from the skin to the first structure entrance (channel length). This will help determine if the rectum is reachable through a posterior sacral approach or a laparotomy/laparoscopy will be needed and if the distal bowel length will reach the perineum after pull-through surgery. It will also determine the length of the common channel whether is 3 cm or less in length, to classify the cloaca as classic or complex (channel length of > 3 cm). The presence, size and location of the vagina should also be determined. Once the surgeon has a good idea of the anatomy of the type of cloaca, surgery is undertaken. It is advisable to do the main repair when the child is stable, growing well and developing normally usually between three and six months of age.  Performing the definitive repair early in life allows for less time with a stoma, easier anal dilatation and the possibility that placing the rectum in the right location early can lead to improved acquired sensation.   

Desmoid Tumors

Desmoid tumors  (DT), also known as aggressive fibromatosis, are benign, locally aggressive tumors, arising from musculoaponeurotic elements, associated with a strong propensity for infiltrative growth and local recurrence.   DT have no tendency to metastasize. There are two incidental peaks: ages 6 to 15 years and puberty to age 40 years. More than 50% of desmoids tumors develop within the first five years of life as an asymptomatic, firm, solid mass. DT can be found on the head and neck, upper or lower extremities, the abdomen or the trunk. The lower extremities are the most frequent sites of manifestation. DT occurs most commonly sporadically, but is often associated with hereditary diseases like familial adenomatous polyposis (Gardner syndrome), familial infiltrative fibromatosis and hereditary dermoid disease. These syndromes are caused by germline mutations of the APC and/or B-catenin gene and mutational analysis of biopsy specimens should be performed. DT may occur at abdominal, intra-abdominal or extra-abdominal location. Abdominal desmoids arise primarily from the rectus and internal oblique muscles and their fascial covering, while intraabdominal tumors arise in the mesentery. Superficial lesions tend to be slow growing, small and rarely involve deep structures. Deep-seated DT tends to be faster growing, larger and involves deeper structures (extra-abdominal). Except fibromatosis colli that tends to regress spontaneously, infantile and extra-abdominal DT is best managed by gross total resection achieving negative margins unless tumor excision is either particularly dangerous or likely to result in significant physical handicap. Surgery provides the best opportunity for long-term event-free survival, though patients undergoing a period of active surveillance do not have an event free survival significantly different from those undergoing surgery or systemic therapy. Radiation or chemotherapy is most often used with recurrent disease or as an alternative to mutilating surgery. Low dose chemotherapy using methotrexate/vinblastine or doxorubicin/dacarbazine therapy is appropriate for children with rapidly growing or unresectable tumors or  symptomatic. Chemotherapy carries adverse effect such as second malignancy, fertility problems, cardiotoxicity and neuropathy. Adjuvant radiation therapy improves local control but is not recommended in skeletal immature children. Younger children have higher recurrence rates when managed with radiotherapy. It is believed they should be treated as low-grade malignancies with documentation of histologic margins and close clinical follow-up. Margin status is not a poor prognostic marker for local recurrence of DT. Other therapies include selective estrogen-receptor modulator, nonsteroidal anti-inflammatory drugs, interferon, tumor necrosis factor alpha and tyrosine kinase inhibitors. Clinical risk factors for poor prognosis in DT include younger age, tumor location (buttock), larger tumor size and proximity to important nerves/vasculature.