PSU Volume 62 NO 01 JANUARY 2024

Contrast-induced Nephropathy

Contrast-induce nephropathy (CIN) refers to an increase in serum creatinine or a reduction in renal function in the form of acute kidney injury seen within the first 24 hours after intravenous contrast exposure for imaging peaking up to five days afterwards. The proportional rise in creatinine is usually 25-30% above baseline in CIN. Creatinine increases within 1-7 days and usually returns to baseline at 7-14 days. Permanent kidney damage rarely develops in these patients. In children the incidence of CIN after intravenous urographic studies is near 15%, while in adults CIN has been reported as the third most common cause of hospital-acquired renal failure in 11% of cases. Contrast used for radiological procedures rely on iodine for their radio-opacity. Iodinated contrast medium may be ionic or non-ionic. Ionic mediums create a high osmolality in blood. This high osmolality in plasma is associated with red blood cell deformation, systemic vasodilation with consequent intrarenal vasoconstriction and direct kidney tubular toxicity. Associated with the pathophysiologic of CIN is renal medullary hypoxia, pre-glomerular vasoconstriction, and the cytotoxic effects of the contrast material by itself. Contrast causes release of renal vasoconstrictors such as adenosine and endothelin resulting in reduction in medullary blood flow leading to medullary hypoxia and tubular cell death. The degree of cytotoxicity is related to length of exposure, high urinary flow rates and after contrast procedures is essential. Hypotension and bleeding aggravates the renal damage secondary to contrast. Reducing the osmolality of contrast agents comes at the price of increased viscosity which reduces glomerular filtration rate and medullary oxygenation with slowing of urinary flow leading to renal retention of contrast which aggravates the cytotoxic effect. Known risk factor for the development of CIN include hyperglycemia (diabetes), nephrotoxic drugs, chronic or intrinsic kidney disease and concurrent acute kidney injury. Hypotension and volume depletion increases the risk of CIN. Repeated exposure to iodinated material and pediatric kidney transplant recipients are also risk factors for CIN. Kidney injury after CIN occurs within minutes of exposure to contrast agents, though the rise in creatinine occurs a day or two latter. Most patients are nonoliguric. Almost all cases are mild with a decline in serum creatinine within 3 to 7 days. Other manifestations of CIN include hyperkalemia, acidosis, and hyperphosphatemia. Fortunately, most CIN cases are self-limited. Management is conservative with dialyses needed in 1% of cases unless the patient has an underlying renal impairment. Mortality rates of 20% has been reported in adults, while there is an associated increase in hospital stay. The risk of developing CIN in hospitalized children with stable mildly diminished renal function is low. It is important to assess renal function before administration of contrast material in children. Serum creatinine and estimated GFR should be assessed. In cases of emergency, a thorough history should be taken to rule out risk factors such as diabetes, volume depletion, and concurrent nephrotoxic drugs use. Prevention strategies include the volume of contrast should be determined by the size of the child. The administration of intravenous fluids (hydration) remains the cornerstone prevention of CIN. The most commonly utilized fluid is isotonic saline. There is no approved drugs for the prevention of CIN. The additional benefit of a number of drugs such as N-acetylcysteine, statins, ACE inhibitors and angiotensin-II receptor blockers, and vitamin C in preventing CIN has not been proved conclusively. Iodixanol is the least nephrotoxic low osmolar agents available. In patients in dialysis the use of iso-osmolar contrast agents to reduce the chances of volume overload are preferred. Major contraindications for use of iodinated contrast agents include history of allergy, impaired renal function, and thyrotoxicosis.     

Perioperative Respiratory Adverse Events

Perioperative respiratory adverse events (PRAE) is a major cause of morbidity and mortality in children undergoing anesthesia and surgery. PRAE have long been a primary safety concern for health care professionals because they can be followed by increased risk for cardiac arrest, prolonged hospital stay, and increased long-term mortality. Age, weight, anesthesia duration, ASA class, pain score, and surgical season are independent risk factors for PRAE development. Children with grade II and III ASA classification show an increased risk of developing PRAE. A detailed history of risk factors taken from the children and families is a good predictor for adverse respiratory events. Immunologic markers of allergic sensitization does not predict adverse respiratory events. Common cold and upper respiratory infections (URI) are common in children with seasonal variations and increase incidence in colder months. URI are the most common reason of surgery cancellation in children. Rhinovirus is by far the most frequent virus causing URI in children. Respiratory syncytial virus infection is a more severe form of respiratory infection that merits attention and careful risk benefit analysis before proceeding with anesthesia and surgery. Viral infection causes airway inflammation that leads to increase secretions, airway susceptibility and bronchial hyperreactivity with increased risk if PRAE.  URI is defined by rhinorrhea, sore or scratchy throat, sneezing, nasal congestion, malaise, cough, or fever above 38-degree C. Performing anesthesia in children with URI increase the risk of PRAE by a factor of 30%, such as laryngospasm, bronchospasm, desaturation, and breath holding. This is more pronounced in infants and premature children. The majority of observational studies have shown that endotracheal tubes are associated with the highest risk of PRAE compared with less invasive airways such as laryngeal or face mask. In general, the risk of PRAE is higher on removal than insertion of airways devices. Neither the use of benzodiazepines for premedication in children with URI nor the use of topical lidocaine to reduce laryngospasm is recommended. Bronchodilators as salbutamol are recommend. Propofol has good airway reflex (laryngospasm and bronchospasm) blunting properties and is, the ideal agent to be used during the induction in children with increased risk of PRAE. Total intravenous anesthesia with propofol is associated with lower PRAE compared to inhalation anesthesia with sevoflurane in healthy children following removal of the laryngeal mask during an awake state. Volatile anesthetics agents have good bronchodilator properties but limited effects in suppressing airways reflexes. Sevoflurane is preferred for induction and maintenance due to its bronchodilator effect. Obese children and adolescents are prone to numerous comorbidities. Respiratory comorbidity is the most common and includes bronchial hyperreactivity and symptoms of severe asthma, increase risk for obstructive sleep apnea and obesity hypoventilation syndrome with impaired lung function indicated by decreased respiratory variables. With regards to the upper airways, it can be narrowed by subcutaneous fat deposition on palatal and pharyngeal soft tissues along with flashy cheeks and a large tongue. Obesity is linked to increase risk of PRAE, airway obstruction, hypoxemia, and difficult mask ventilation. Obese children are also vulnerable to airways infections and gastroesophageal reflux. Bronchial asthma is not only more common among obese children but also followed by increased risk for bronchospasm after general anesthesia with tracheal intubation. To reduce the incidence of PRAE in obese children the use of short-acting opioids and nonopioid analgesics along with regional anesthesia should be used. Noninvasive airway management protective mechanical ventilation, and complete reversion of neuromuscular blockade and awake extubation also is beneficial to prevent PRAE. Postoperative care and continuous monitoring of oxygenation and ventilation are mandatory and can accelerate recovery after surgery in obese children. The increased risk of PRAE also occurs with children with sleep disorder breathing such as sleep apnea syndrome, central sleep apnea and nocturnal hypoventilation. Most of these cases of PRAE are limited to children with sleep disorders undergoing tonsillectomy and adenoidectomy which are recommended to stay in-hospital overnight for observation. Most uncomplicated children with mild URI can typically proceed with elective anesthesia. Most recommendations include that for a moderate to severe URI elective anesthetics should be delayed two to four weeks, and for respiratory syncytial viral or lower airway infection the delay should be at least six weeks. The risk of PRAE can be predicted using the COLDS score.  

Esophageal Anastomotic Stricture

Anastomotic stricture (AS) is defined as a narrowing at the level of the esophageal anastomosis detected by barium contrast study and/or endoscopy, associated with significant functional impairment and symptoms. AS remains the most common complication following operative repair of esophageal atresia in children occurring in 20-50% of cases. Though there are some specific predictors of AS formation, the majority of patients continue to manifest this complication without risk factors. Predisposing factors for the formation of anastomotic stricture identified include prematurity, low birth weight, presence of VACTERL association, anastomotic leakage, anastomotic tension, increase length of esophageal gap between the upper and lower pouch (> 1.5 cm), type of suture material (such as silk), traction technique repair (Foker), use of transanastomotic tube, and gastroesophageal reflux disease (GERD).Vascular compromise leading to AS affects especially the lower esophagus, which has a segmental blood supply from the aorta or the intercostal blood vessels. Too much mobilization risk devascularization. No association between acid suppression duration and stricture formation has been found. Prophylactic acid reflux therapy do not reduce the incidence of esophageal stricture after repair of esophageal atresia. After an esophageal anastomosis is quite natural to see a degree of narrowing after repair due to circular wound contraction. Children with AS develop feeding and swallowing difficulty, drooling, regurgitation, vomiting, coughing, and choking during feeding, regurgitation, apneic spells, foreign body impaction, and poor weight gain. These symptoms can also be associated with esophageal dysmotility, recurrent tracheoesophageal fistula, severe tracheomalacia, gastroesophageal reflux, swallowing incoordination, laryngeal cleft, or vocal cord dysfunction. Initial workup of symptomatic children with suspected AS should include contrast esophagogram, followed by flexible upper endoscopy, rigid or flexible tracheoscopy as needed. Most surgeons perform an esophagogram between 5 and 10 days after repair of esophageal atresia to rule out the presence of an anastomotic leak. An esophageal anastomotic stricture index (EASI) has been developed using fluoroscopic evaluation of the upper gastrointestinal tract in the early postoperative period. Two pouch ratios are generated using the narrowest stricture diameter well filles with contrast, divided by the maximal upper (U-EASI) and lower respective pouch diameter (L-EASI). A ratio of 0.25 means that the diameter at the anastomosis is 25% of the diameter of the patient normal esophagus. The lower pouch stricture ratio (L-EASI) is superior in determining the prognosis for patient with AS. Since the upper pouch is dilated due to the chronic obstruction in utero, the lower pouch provides a more accurate measurement of the real esophageal diameter. An L-EASI les than 0.30 is highly correlated with need of esophageal dilatation. The EASI is simple, reproducible tool to identify children at risk of AS, guide frequency of follow-up and schedule further contrast studies need. The treatment of choice for patients with AS after esophageal atresia repair is dilation, typically performed in the symptomatic patient with radiologic evidence of stricture. Prophylactic dilatation of the anastomosis has no benefit in the prevention of symptomatic stricture. Primary goal of esophageal dilation is to achieve symptoms relief, permit maintenance of age-appropriate oral nutrition, and reduce the risk of pulmonary aspiration. Two types of dilators are used: fixed diameter push type dilators (bougie dilators) and radial expanding balloon dilators. Bougie dilators are weighted (tungsten filled) or wire-guided dilators. Blind passage of non-wire-guided bougies may lead to a higher risk of perforation and to incorrect passage of a dilator into the trachea. Wire guided dilation provides assurances the dilator is following the line of the esophageal lumen. Bougies are reusable. Balloon dilators exert radial forces, the force is delivered simultaneously over the entire length of the stricture and are single use. Balloon dilatation is performed under fluoroscopy or endoscopy. Most frequent reported complication of dilation is perforation, hemorrhage, and bacteremia (0.1-0.4%). Balloon dilation requires fewer procedures than bougies. Through the scope balloon dilatation is currently the most frequently used method of therapy. Risk of perforation is minimized by limiting dilation to no more than three sequential dilators size once moderate resistance is encountered (`rule of three'). Severe GERD is frequently observed in cases of severe AS due to corrosive esophagitis or long-gap esophageal atresia AS. Cicatricial shortening of the esophagus represents an important cause of GERD needing PPI treatment to treat esophagitis and acid damage, with a great need of fundoplication if the problem persists due to reflux. Intralesional steroid injection (triamcinolone) benefits is controversial in reducing recurrent stricture formation. Intralesional steroid injection with dilation is well tolerated, improves AS diameter when compared with dilation alone, but effect is limited to the first three injections. Evidence is lacking to suggest a benefit to systemic steroid use in AS. Mitomycin C is an antineoplastic antibiotic with anti-fibroblastic activity. Topical application of Mitomycin C to the stricture as adjunct to dilatation produce significant symptoms improvement and a reduction in the need of dilatations. Endoscopic incisional therapy with dilation can be used in short or asymmetric strictures. Esophageal stenting is a promising tool for management of refractory or recalcitrant AS creating prolonged lumen patency and better oral feeding. Patient tolerance and migration are adverse event with this therapy. Children who fail to respond to all conservative strategies, including responding to 7-10 dilation sessions, require surgical intervention (3-7%), which is commonly perform with resection and re-anastomosis. Long segment (>3 cm) strictures will need staged approach with segmental resection and traction process. Other causes of esophageal stricture include congenital esophageal stenosis, disk battery ingestion, peptic and eosinophilic esophagitis, actinic or neoplastic esophageal stricture, and epidermolysis bullosa.     

PSU Volume 62 No 02 FEBRUARY 2024

Total Colonic Aganglionosis

Hirschsprung's disease (HD) is characterized by bowel obstruction. Diagnosis is confirmed by finding aganglionosis of the inert-myenteric plexus with absent calretinin staining in rectal biopsy. Development of result from abnormalities in the colonization of the enteric nervous system with faulty neuroblast migration during fetal live. Most cases involved aganglionosis of rectosigmoid. Total colonic aganglionosis (TCA) with or without distal small bowel involvement occur in 8% (5-15%) of all cases of HD with a 1:1 gender involvement. Within this group, those with a transitional zone within 5 cm of the ileocecal valve are TCA, with a transitional zone of more than five cm from ileocecal valve to 20 cm from ligament of Treitz is called small intestinal HD, and a transitional zone within 20 cm of the ligament of Treitz is recognized as total intestinal HD. Digestive autonomy may be achieved in children who have at least 80 cm of remnant ganglionic small bowel. TCA involvement has significant morbidity and mortality than short segment HD requiring more complex medical and operative management. Improvement in management is associated with earlier diagnosis of TCA, earlier management of enterocolitis and improvement in supportive care. TCA is regarded as a genetic, sex modified, multifactorial condition with a variable severity and incomplete penetrance of a number of genes. Contrary to other belief, the use of the appendix for diagnosis of TCA has a 100% sensitivity, specificity, positive predictive value, and negative predictive value, but should not be used as the sole diagnostic indicator of TCA as the absence of calretinin corroborates the diagnosis. The appendix should not be removed completely, just the distal 1 cm, in case is needed later for bowel management (Malone). The surgical treatment of TCA has two goals: remove the aganglionic bowel, and to provide children with a good quality of life which is reflected in an acceptable frequency of bowel movements, fecal continence, and no symptoms of enterocolitis. Most children with TCA are managed with a diverting ileostomy with ganglion cells from diagnosis. These children with ileostomy struggle with growth and fluid losses, and benefit from a comprehensive nutritional evaluation and optimization prior to a pull through. Prior to pull-through the consistency of stool should thicken to an apple sauce consistency. This can occur between 9 and 12 months after the ileostomy. Pectin and water-soluble fiber can increase the consistency and volume output. Loperamide is also utilized to increase consistency since it increases gastrointestinal transit time by reducing activity in both the longitudinal and circular muscle fibers, as well as reducing secretions of gastric acid, bile and pancreatic enzymes thus reducing the luminal fluid content. Proceeding with the pull-through for TCA in HD once the child is growing well and the stools have started to thicken is the best recommendation, the timing of which usually occurs sometimes between six and 18 months of life. Once ready for pull-through the surgery is generally performed without a covering stoma, unless anatomic or technical decisions favor a proximal diversion. There is no consensus on the preferred procedure to perform in TCA. Long term TCA children may only achieve a good outcome in 50-60% of cases. Reconstruction procedure for TAC encompass two groups: those that retain various length of aganglionic colon as a form of patch to improve absorptive capacities (Kimura, Martin, and Duhamel), and procedures that use small bowel ganglionic bowel such as the straight ileoanal (Swenson, Soave, transanal or laparoscopic) or J-pouches with short limb (4-5 cm) pull-through. The most commonly performed surgical reconstructions in TCA are J-pouch with ileoanal anastomosis, straight ileoanal anastomosis and Duhamel. Contemporary expertsÕ recommendations support straight ileoanal pull-through as preferred conduit, which should be diverted if constructed in the newborn period. The Duhamel procedure has been popular for TCA so long as a spur is avoided to avoid postoperative obstructive symptoms. The residual aganglionic segment of rectum can result in constipation/fecalomas and incontinence. Recurrent or chronic enterocolitis and the need for intrasphincteric botulinum injections is less common after the Duhamel operation. The Martin procedure with a long side to side anastomosis of ganglionic ileum to aganglionic colon has been abandoned due to technical difficulty, high complication rate and need of multiple operations. The same has happened with the Kimura colonic patch procedure. The Swenson procedure leaves the least amount of aganglionic bowel behind but due to the low dissection the sphincters can be damaged causing incontinence, or damage to other structures such as vagina and urethra. Pena suggest an approach for TCA consisting of colectomy with straight ileoanal anastomosis and ileostomy at presentation in the newborn period. Closure of ileostomy is performed when the child is toilet trained for urine and willing to tolerate rectal irrigations. A covering enterostomy significantly reduced the incidence of postoperative complications such as anastomotic leak. Most frequent early complication among patients without a protective stoma is perineal rash. Postoperative care must consider an aggressive approach to perineal skin care (cyanoacrylate-based liquids), optimization of stool content output with pectin/water soluble fiber, avoidance of foods with high sugar content, sodium supplementation, and use of loperamide for frequent stools. Enterocolitis is overall the most common postop complication, followed by fecal incontinence and soiling. Over time children with TCA or long-segment aganglionosis do not suffer from worse fecal incontinence in general. A difference in stool consistency may underlie the association between liquid fecal incontinence and TCA and constipation in children with rectosigmoid aganglionosis. General quality of life is comparable on reaching adulthood in HD patients.    

Vaginal Reconstruction

Absence of the vagina in children is rare. Vaginal reconstruction in children is needed in patient with congenital agenesis of the vagina (aplasia of Mullerian ducts associated with the 46 XX Mayer-Rokitansky-KŸster-Hauser syndrome), complete androgen insensitivity syndrome (46 XY testicular feminizing syndrome), congenital adrenogenital syndrome with absent or hypoplastic vagina, after pelvic tumors or posttraumatic injury. In all these cases a vaginal replacement is needed. The proposed, motivation for performing feminizing genitoplasty procedures earlier in life is to produce the best psychological outcome for the child by helping them to avoid stigma, optimizing future self-esteem and sexual satisfaction, and reducing psychological risk. The most common condition needing vaginal reconstruction is congenital adrenal hyperplasia (40%) with a median age of 2.4 years and almost 75% performed in patients under age 12. Recent studies demonstrate a low 30-day postoperative complication (6%), readmission (7.9%) and reoperation (4%) rate after vaginoplasty in children. Surgically assigning anatomical gender before a patient has capacity to make informed decisions regarding their own gender identity can be detrimental to psychological well-being. The goal of vaginal reconstruction surgery is a technique with a very low morbidity and complications as well as no mortality. Its aim is the creation of a vagina that requires a simple and non-psychologically traumatic nursing that gives the possibility to perform coitus without pain, discomfort, and embarrassing secretions. In children basically three types of surgical procedures has been developed for vaginal reconstruction: the inlay skin-graft technique, the use of grafts (peritoneum, bladder buccal mucosa, amnion), and replacement using bowel (colon or ileum). The split-thickness skin graft is indicated only in cases of small reconstructions of the distal vaginal tract since it requires lubrication, prolonged vaginal dilations, or sexual intercourses to maintain patency. Using this technique contracture, shortening, bleeding and dyspareunia is frequently found. The amnion graft or the pelvic peritoneum graft should be avoided in children since those tissues are very fragile and require vaginal stenting and dilatations. Some nonsurgical techniques to create an artificial vagina, such as the Abbe-McIndoe procedure (perineal cleavage covered with a skin graft) or simply mechanical dilatations are difficult to apply in preadolescent children due to the long period of vaginal dilatations and in most cases subsequent surgical management is needed. Most of these cases need a well-motivated patient. These procedures are complicated by high grade of vaginal stenosis, flap loss, graft shortening, unsightly donor site scars, the possibility of hair in the vagina, deficient lubrication, and potential for squamous cell carcinoma in the graft. With paucity of local tissues, vaginal reconstruction may require utilization of donor material. Autologous buccal mucosa is an excellent graft material because of its robust vascularity and elasticity. With excellent color and texture matching to genital and vaginal skin, buccal mucosa generates moist, hairless, non-keratinized neovaginal mucosa. The tissue is readily available, and the donor site scar are completely hidden inside the mouth. Autologous buccal mucosa vaginoplasty also avoids abdominal surgery with no risk for bowel obstruction, prolapse, or anatomic leak. Autologous buccal mucosa can be utilized in distal vaginal augmentation in patients with distal vaginal agenesis or urogenital sinus vaginal reconstruction as well as offer a novel technique for total neovagina creation in cases of vaginal agenesis, the secondary repair of vaginal stenosis after previous vaginoplasty, as well as for the creation of the external genitalia when tissues are lacking. Buccal mucosa can be used to augment a foreshortened vagina, create a total neovagina, or in the repair of a vaginal stricture after prior vaginoplasty. Also, the use of buccal mucosal graft coupled with intravaginal wound vacuum therapy offers a promising new approach resulting in an excellent engraftment rate. In pediatric patients isolated intestinal segments provides an ideal tissue for an artificial vagina creation. The sigmoid segment is the segment of choice as excellent tissue for vaginal replacement, with the ileal bowel when the sigmoid is not available. Ileum produces more abundant and less lubricating secretions than the sigmoid segment and is also more fragile causing bleeding after intercourse. Sigmoid colon is easy to mobilize, offers a more appropriate size vaginal canal and permits to obtain an adequate length without problems. The usual length utilized is 10-12 cm of sigmoid colon with good functional results and low risk of diversion colitis. In colovaginoplasty the secretions are initially excessive, but after two to 3 months they normalized. Colonic mucosa is more resistant to trauma and a mould is not needed to maintain patency. Using colon, the possibility of end-to-end anastomosis between the neovagina and the uterus in cases of a patent uterus is possible. The ideal surgical time for vaginal reconstruction is after puberty.     

Low-Pressure Pneumoperitoneum

Over time, there has been a substantial increase in the utilization of laparoscopy as a surgical approach in pediatric patients. Carbon dioxide (CO2) serves as the insufflation gas, and the absorption of CO2 can lead to hypercapnia. The establishment and maintenance of a stable pneumoperitoneum play a crucial role in minimally invasive surgery, as it is imperative for creating adequate operative space to safely manipulate instruments. The induction of hypercapnia through CO2 insufflation results in an elevation of cerebral blood volume and cerebral blood flow velocity. Elevated intraabdominal pressure during CO2 pneumoperitoneum contributes to increased intracranial pressure. CO2 insufflation during laparoscopy has both mechanical and pharmacological effects on the cardiorespiratory system. Hypercapnia, resulting from CO2 absorption into peritoneal blood vessels, induces an increase in heart rate (HR) and mean arterial pressure (MAP) through heightened release of catecholamines. Even after desufflation, both HR and MAP remain elevated due to a delay in the reduction of CO2 levels. Hypercapnia induces moderate vasodilation in most tissues and marked vasodilation in the brain. However, CO2 pneumoperitoneum may lead to side effects such as pulmonary hypertension, hypercapnia, and acidosis. To mitigate these effects, patients are hyperventilated. Hemodynamic changes observed during pneumoperitoneum with pressures exceeding 8 mmHg in children include increased heart rate and blood pressure, along with decreased cardiac index (CI). CO2 insufflation, with the operating table in the reverse-Trendelenburg position while maintaining constant minute-ventilation, results in significant increases in CI, HR, MAP, and peak inspiratory pressure (PIP). The increase in CI is primarily due to an elevated HR. These effects are influenced by both the intraabdominal pressure (IAP) magnitude and the neurohumoral effect induced by hypercapnia. An IAP above 10 mmHg in children results in decreased venous return, left ventricular preload, left ventricular cardiac output, and aortic blood flow. Additionally, it leads to changes in pulmonary function due to diaphragm elevation, reduced functional residual capacity, and increased alveolar dead space. Low-pressure pneumoperitoneum (LPP) during laparoscopy has been introduced to minimize intraoperative hemodynamic changes and neuroendocrine stress reactions. LPP (below 10 mmHg), facilitated by deep neuromuscular blockade, is considered safe and feasible while offering physiological and clinical benefits. These advantages include lower postoperative pain scores, reduced incidence of infectious complications, and decreased opioid consumption. Patients operated at LPP exhibit lower surgical site hypoxia and inflammation markers, along with less impaired early postoperative cytokine production. LPP results in less tissue hypoxia, lower circulating tissue damage markers, and a less impaired postoperative innate cytokine production capacity. Increased IAP during laparoscopy predominantly affects the cardiovascular and pulmonary systems. The primary impact of LPP lies in postoperative pain and analgesic consumption. Post-laparoscopic pain can be categorized into three components: referred shoulder pain, superficial or incisional wound pain, and deep intra-abdominal pain. Different types of pain may correspond to distinct etiologies, with referred pain often attributed to CO2-induced diaphragm or phrenic nerve irritation. Deep intraabdominal pain is primarily caused by bowel traction, abdominal wall stretch, and compression of intraabdominal organs. Symptoms attributable to pneumoperitoneum pressure may also contribute. While the use of LPP may significantly increase operative time due to reduced surgeon visibility, its implementation is vital in addressing postoperative pain and promoting optimal patient outcomes.

PSU Volume 62 No 03 MARCH 2024

Ovarian Dysgerminoma

Ovarian tumors are rare in children representing nearly 50% of all ovarian masses with 90% being benign. Germ cell tumors of the ovary are the most frequent histological type (60-70%) with teratoma as the main pathology. Dysgerminoma is the most common malignant germ cell tumor of the ovary representing only 2% of all ovarian cancers in children. It is most frequent during adolescence and young adulthood with a peak incidence of 15-19 years of age. Ovarian dysgerminoma is the female counterpart of testicular seminoma derived from primitive germ cells. Dysgerminoma are often found in association with gonadal dysgenesis and abnormal ovaries that contain gonadoblastoma. Most females with ovarian dysgerminoma present with non-specific symptoms, or most commonly abdominal pain, abdominal distension, menstrual irregularity, decreased appetite, vomiting and a palpable pelvic abdominal mass. They grow rapidly, the tumor is quite large and may be associated with complications like rupture, hemoperitoneum or torsion presenting as an acute abdomen. Though dysgerminoma are hormonally inert, a few cases have presented with precocious puberty due to elevated estradiol levels secreted by syncytiotrophoblastic giant cells and stromal luteinization.  Most tumors arise from the right ovary. Dysgerminoma are bilateral in 10-15% of cases. Ovarian dysgerminoma may be associated with dysgenetic gonads that contain gonadoblastoma. Elevation of serum lactate-dehydrogenase (LDH), cancer-antigen-125 (CA-125), beta-subunit-human-chorionic-gonadotropin (B-hCG), S-100 protein, neuron-specific enolase (NSE) and placental-alkaline-phosphatase (PALP) are frequent findings in children with dysgerminoma. Alpha fetoprotein is not elevated. With elevated B-hCG pregnancy is frequently diagnosed erroneously. Pregnancy and dysgerminoma might exist together in 20-30% of cases. LDH and PALP when elevated are used as tumor markers to follow up these patients.  Diagnosis of an ovarian mass is done with CT-Scan and/or MRI. Findings are of a large well-encapsulated, multilobulated, purely or predominantly solid mass. It demonstrates an attenuation similar to muscle and nonspecific signal intensity on T2-weighted images. The characteristic imaging feature of dysgerminoma is fibrovascular septa in the tumor appearing as hypodense lines on T2-weighted images and show intense enhancement on contrast-enhanced CT and MRI images. Ovarian dysgerminoma may also contain necrosis, hemorrhage, small cystic change, or calcifications. Grossly, dysgerminomas are typically large and solid with a homogenous creamy yellow to pink or tan and lobulated appearance. On microscopic examination the neoplasm is characterized by delicate fibrous septa, along which are lymphocytes that intersect aggregates of polygonal clear cells with well-defined cytoplasmic borders and angulated nuclei with prominent nucleoli giving an alveolar pattern appearance. The histology is frequently referred to as "fired eggs". The presence of calcifications suggest gonadoblastoma. The finding of relatively large, round, or ovoid, "mulberry-like" calcific foci should suggest the presence of gonadoblastoma.  Most cases of ovarian dysgerminoma present as stage I. Management of dysgerminoma is primary surgical excision of the mass with unilateral salpingo-oophorectomy. Fertility sparing surgery is encouraged as frontline therapy when feasible and clinically appropriate without compromising the prognosis. The surgical approach warrants exploration of the peritoneal surface for nodules, prominent lymph node removal, omentectomy if the tumor is wrap with omentum, contralateral ovarian biopsy if abnormal and cytology of the ascitic fluid if present. Overall survival after surgery for stage I tumor is 92%. Dysgerminoma most frequently metastasize to the peritoneal cavity, omentum (86%), pelvis, and abdomen as well as retroperitoneal lymph nodes. In higher stage dysgerminoma (FIGO stages II-IV), the guidelines recommend fertility sparing surgery followed by four cycles of chemotherapy. Dysgerminoma are radio- and chemo-sensitive. Radiotherapy is not used as frontline therapy due to risk of secondary malignancy, premature ovarian failure, and a significant impact on future fertility. Standard of care of management of advanced stage dysgerminoma (disease that has spread outside of the ovary) is postoperative adjuvant chemotherapy with either carboplatin or cisplatin combined with etoposide and Bleomycin. Cisplatin based therapy is associated cardiovascular disease, development of secondary malignant neoplasm in survivors, ototoxicity, nephrotoxicity and gonadotoxicity (premature ovarian failure). Patients with advanced stage dysgerminoma have an excellent five-years event free survival and overall survival across all age groups with both cisplatin and carboplatin therapy. Clinical trial data support the use of carboplatin-based therapy with or without Bleomycin as frontline treatment for all patients with advanced stage dysgerminoma to minimize treatment related toxicity without significantly compromising therapeutic efficacy.

Pouch Failure

Children with ulcerative colitis, familial adenomatous polyposis and total colonic aganglionosis benefit from ileal pouch-anal anastomosis (IPAA) as standard restorative procedure. Most of these reconstructed ileo anal pouch report a good quality of life with excellent outcomes. A significant number of patients develop short, and long-term complications such as anastomotic leak or stricture, fistula, pelvic sepsis, recurring pouchitis, development of perianal Crohn disease, and pouch dysfunction. All of these complications can lead to pouch failure which has been reported to occur in up to 15% of all patients (5-15%). Pouch failure is defined as the need for pouch resection, permanent diversion, or a revision/redo of the pouch procedure. The most common causes of pouch failure have been pelvic sepsis, poor pouch function, pouchitis and de novo Crohn's disease. Patients who develop perineal Crohn's has the highest rate of pouch failure (47%). Pouch failure has no significant difference in gender distribution. Complications leading to pouch failure can occur early (26%) or late (76%). In early failures, pelvic sepsis due to anastomotic complications (bleeding, stapler malfunction, ischemia, tension) play a major role. Anastomotic leakage is an independent risk factor for pouch failure. In late pouch failures, pouch-related fistulas with chronic sinus formation plays a major role. Primary sclerosing cholangitis associated with ulcerative colitis can increase pouchitis rates as well as the risk of postoperative sepsis. Patients with pouch dysfunction present with a significant decrease in their quality-of-life reporting bowel movement of more than 20 times per day, urgency, tenesmus, draining fistulas, hematochezia, and abdominal pelvic pain. Patient report food, work, and sexual restrictions, leading to psychological impairments and general debilitation. Once pouch failure ensues the child has several alternatives: reconstructing the pouch, permanent ileostomy with pouch excision, or leaving the pouch in situ. A few patients with minimal inflammatory conditions can undergo pouch excision with ileoanal straight reconstruction depending on the fibrotic state of the pelvis. Redo pouch surgery is lengthy and complex with an overall morbidity rate of 40% after salvage pouch surgery. Most common complication of redo surgery is pouch fistula, stricture, pelvic abscess, and pouch-vaginal fistula. Complications are more frequent in those who had pouch excision with creation of a new pouch compared with those whose old pouch was utilized. Also, the rate of bowel incontinence after redo surgery is higher. Pouch failure is significantly associated with Crohn's disease-like pouch inflammation, biologic use, and pouch revision. Pouch excision with permanent ileostomy is a complex procedure because of the need for reoperation within the pelvis and hence the potential for damage to pelvic structures and risk of septic complications. Leaving the pouch in situ has the potential drawback that patients may experience symptoms of seepage from the anal canal (mucous drainage and anal pain), and the risk of harboring cancer in the pouch. A permanent ileostomy is an alternative option in circumstance where pouch excision may not be feasible or advisable patients with incontinence, outlet obstruction, or fistula are better served by pouch excision because they continue to experience troubling anal symptoms after leaving the pouch in situ. Sexual function is kept better after a pouch left in place than after pouch excision. In general pouch excision with permanent diversion is the treatment of choice for patients with pouch failure since its associated with improved quality of life and prevents perineal symptoms, including anal pain and seepage. Leaving the pouch in site is an option when concern about reoperation in the pelvis could cause significant urinary and sexual complications. The long-term risk of developing dysplasia in the retained pouch seems to be minimal, though pouch endoscopic surveillance should be performed to ensure the early detection of any silent neoplastic transformation of the pouch or residual anorectum.

Refeeding Syndrome

Refeeding syndrome (RS) is an acute metabolic disturbance and potentially life-threatening condition which occurs upon sudden and rapid reintroduction of oral, enteral, or parenteral nutrition after prolonged fasting or suboptimal feeding. This disease is characterized by a rapid shift in electrolyte and fluid balance that can cause a range of symptoms and complications including cardiac arrhythmia, shortness of breath, seizures, and even death. Body goes from a catabolic to an anabolic state. The result is that the body creates an intracellular demand for metabolites such as inorganic phosphorus (P), potassium (K), magnesium (Mg) and thiamine (Vitamin B1). This traduces into a deficient state causing hypophosphatemia, hypokalemia, and hypomagnesemia. Re-eating, especially carbohydrates raises insulin levels which promotes glucose uptake and utilization by cells, eventually resulting in rapid changes in electrolytes and fluid balance. Potassium, magnesium, and phosphate enter the cell causing a reduction of these electrolytesÕ levels in the blood. RS in adolescents and young adults is generally associated with marked malnutrition, mainly anorexia nervosa. Other children at risk are those with celiac disease, cancer, cerebral palsy, congenital heart or lung disease, postoperative status, and Crohn's illness. RS can manifest clinically as a mild electrolyte disturbance without significant clinical symptoms, or as a severe electrolyte disorder leading to severe organ failure such as respiratory and cardiac failure, cardiac arrhythmias, seizures, muscle weakness, horizontal nystagmus, and encephalopathy (Wernicke's). The mortality after developing RS can be as high as 70%. Children at high risk for developing RS include those with significant reduced energy intake for up to ten days before reintroduction of nutrition, as well as those that are malnourished. Patients in the pediatric intensive unit are at risk of developing RS at the time of feeding due to the prevalence of malnutrition in this population. The longer in PICU the higher the incidence of developing RS. To establish the diagnosis of RS the American Society for Parenteral and Enteral Nutrition has enunciated the criteria for RS as a decrease in any 1, 2 or 3 of serum phosphorus, potassium or magnesium levels by 10-20% (mild RS), 20-30% (moderate RS), or greater than 30% (severe RS), and/or organ dysfunction resulting from a decrease in any of these and/or due to thiamine deficiency (severe RS); and occurring within five days of reinitiating or substantially increasing energy provision. The incidence of RS among critically ill children at risk is high (46%) and severe most of the time. The PICU length of stay and acquired infections were higher in children who developed RS than in those at risk who did not. Main management strategies for RS in children involve a multidisciplinary approach with careful monitoring and supportive care to prevent and treat the complications of this condition. Management of eating disorders as anorexia nervosa seen in adolescent kid and young adults consist in the gradual restoration of weight and the prevention or treatment of clinical complications such as unstable vital signs, laboratory, and cardiac anomalies. Despite this there is no clear consensus in management. Refeeding should be started at a low level of energy replacement with vitamin replacement started with refeeding and continued for at least 5-7 days. Correction of fluid and electrolytes imbalance prior to feeding is not necessary and should be done as the same time as feeding. Prevention of RS requires small amounts of low-calorie fluids, checking electrolytes and thiamine supplementation. This can be accomplished by gradually increasing the number of calories in the diet and monitoring potassium, magnesium and phosphate.RS is a serious condition that can be managed with careful monitoring and controlled treatment. 

PSU Volume 62 NO 04 APRIL 2024

Fish Skin for Burns

The annual burn incidence rate in the US is approximately half a million people, including 40,000 hospitalizations as a result of burn-related injuries and 3400 deaths. The main treatment for deep dermal and full thickness burn injury is early excision and coverage with autologous split skin grafting or flaps. This avoids common complications like sepsis, multi-organ failure, and acute kidney injury.

When the wound is extensive, availability of autologous skin becomes a problem, and allogenic and xenogeneic skin for temporary coverage after excision will be needed. A variety of dressings are currently available for superficial partial-thickness burns such as silver-impregnated, alginate, hydrocolloid, hydrogel, silicone-coated nylon, polyurethane film, or biosynthetic dressings without a gold standard being defined.

As a matter of review, autografts are skin grafts that are transferred from the same person with the wound but a different healthy location, allografts are skin grafts transferred from a different person used as a donor (cadaver), and xenografts are transferred from an animal such as pigs, cattle, or fish. Xenografts are termed cellular and/or tissue-based products.

Human cadaver and pig skin are the major source of temporary coverage for deep and full thickness burn injury. Application of human and pig skin grafts carries a risk of auto-immune response along with a risk of viral and bacterial disease transmission. Skin from a cadaver has a limited supply and is expensive.

An alternative for grafting extensive areas of burned skin is using acellular fish skin (xenograft). Acellular fish skin has been described as effective, safe, efficient skin substitute free of the risk of transmission of viral disease and auto-immune reactions. Acellular fish skin has also been utilized with success in the healing process of acute and chronic wounds like diabetic foot ulcers and non-healing leg wounds.

The most exceptional property of acellular fish skin grafts that makes it efficacious is its lipid profile. Fish skin is rich in Omega-3 polyunsaturated fatty acids, eicosatetraenoic acid, and docosahexaenoic acid, which are highly effective as antimicrobial agents even against methicillin-resistant Staphylococcus aureus, and in modulating the inflammatory response of the acute wound healing stage.

Fish skin maintains its three-dimensional structure and is highly porous, providing an extracellular matrix composed of glycosaminoglycans, proteoglycans, fibronectin, and growth factors which allows the migration of autologous cells to promote the proliferative and epithelialization phases of the burn healing process.

Acellular fish skin grafts are also very porous, having about 16.7 large diameter apertures for every 100 µmm allowing it to properly adhere to human skin and promote the passage of human fibroblasts, which are known to play an important role in effective wound healing.

Fish skin is stored at room temperature, has a shelf life of three years, and is marketed as an off-the-shelf product. This characteristic makes fish skin ideal in the setting of combat casualties where cadaver or pig skin is not practical due to the short shelf life.

The fish graft contracts slightly after salination and insertion into the wound bed, so it is recommended that pre-wetting takes place before the product is applied so that shrinkage occurs before applying it to the burn patient. Acellular fish skin graft is harvested from two major species such as the Nile Tilapia or the North Atlantic cod.

Applications for the use of fish skin graft include burn skin reconstruction, chronic and oral wound, hernia repair, breast reconstruction, and dura mater reconstruction. Acellular fish skin presents an effective treatment option in burn management since studies indicate accelerated wound healing, pain, and discomfort reduction, decrease in necessary dressing changes, as well as treatment-related costs.

The novel approach of acellular fish skin xenografts may represent an effective, low-cost alternative for the management of deep and full thickness burns since existing evidence indicates accelerated wound healing, reduction of pain and necessary dressing changes, as well as improved long-term outcomes. Wounds managed with fish skin graft have better functionality long-term and aesthetically superior when compared with those managed using other cellular tissue-based products.

PICA

The term Pica is derived from a brown-billed magpie bird, famous for its habit of indiscriminate gathering and eating a variety of objects to satisfy its hunger and curiosity. In the medical argot, Pica refers to the persistent, compulsive craving for and the ingestion of substances usually considered inedible.

The behavior of a patient with Pica is discordant with cultural practices and continuous beyond the normal developmental phase of occasional indiscriminate and experimental mouthing and swallowing over a period of at least one month. Pica occurs worldwide with a prevalence greatest in children eighteen months to six years. It is more common in blacks than whites and more common in boys than girls.

20-30% of all children from one to six years of age have practiced Pica. In the USA, less than 10% of children older than 12 years of age meet the diagnostic criteria for Pica. Pica is more common than generally appreciated, with prevalence higher in Africa compared to the rest of the world. It is also more common among low socioeconomic level children and pregnant women.

Among the etiology and pathogenesis of Pica are hunger, disturbance in the mother-child relationship, relief of anxiety by oral gratification, and an infantile hand-to-mouth behavioral response to family stress or as an expression of oral fixation. Others believe it is an attention-seeking device. Pica is common in mentally handicapped children, and the prevalence correlates with the severity of mental retardation. It is also more common in those with autistic spectrum disorder, attention deficit, schizophrenia, obsessive-compulsive disorder, and depression.

There is an association between Pica and iron deficiency. Children with sickle cell anemia are at greater risk for developing Pica. Children with Pica are highly selective, and the ingested material depends on the availability in the environment as well as conscious selection factors. Substances that may be craved by children with Pica include clay (geophagia), raw starch, dirt, ice, raw potatoes, hair (trichophagia), fibrous plant roots, sand, pebbles, glass, soap, feces (coprophagia), vomitus, and the list goes on. By far, the most common are clay and raw starch.

In the majority of cases, the physical exam is normal. Other signs of Pica include pallor, anemia, anorexia, easily fatigability, malnourishment, developmental delay, abdominal discomfort, or pain if large quantities of inedible substances are ingested. Bezoars may lead to intestinal obstruction needing surgical evaluation.

General labs are indicated, including blood lead levels, along with simple abdominal films looking for filling defects or radio-opaque material in the gastrointestinal tract. Complications depend on the substance ingested. Ferrous deficiency anemia is a common complication since the binding of the ingested clay to the iron causes an inability to be absorbed properly. This is particularly important in pregnant women after geophagia.

Pica is a risk factor for accidental ingestion of toxic substances such as lead in pencils and toys. Malnutrition results from Pica. Other electrolyte abnormalities identified in children with Pica include zinc deficiency, hypokalemia, hyperkalemia, hyperphosphatemia, and metabolic alkalosis. Other complications include parasitic infestation, tooth abrasion, constipation, and bowel obstruction. Complications from bowel obstruction and perforation from masses of consumed matter in the stomach and intestine might need surgical intervention.

There is no gold standard for the management of Pica. Management of Pica includes training and supervision while eating, attention to individual emotional needs and stress, behavioral therapy, family counseling, and psychotherapy.

Rhabdoid Tumors

Rhabdoid tumors (RT) are rare and highly aggressive malignant tumors of embryonal origin typically diagnosed in early childhood. Initially diagnosed in 1978 as a RT of the kidney, subsequent cases identified tumors with similar histology in soft tissue and central nervous system (CNS). In 1995 an atypical teratoid/rhabdoid tumor was described in the CNS. RT are often diagnosed in late stages carrying a poor prognosis.

These tumors are known for being particularly aggressive and fast-growing. The three most common site for RT are the kidney, CNS, and soft tissue (Extrarenal). Frequent sites for extrarenal RT include skin, liver, and lung, although tumors in almost all soft tissue have been reported. Peak incidence of RT is between one and 4 years of age. Classic RT have been diagnosed also in adults.

Atypical teratoid/rhabdoid tumor (AT/RT) is a rare and aggressive type of embryonal tumor of the CNS occurring in children. AT/RT represent brain tumor in early childhood, which is the most common CNS primary malignant tumor in children less than 6 months of age. Spinal AR/RT has the following characteristics: children has cauda equina syndrome (lower back pain, muscle weakness and numbness in the lower limbs, loss of sensation in the saddle area, bladder and bowel dysfunction, and sexual dysfunction), the mass invaded the thoracolumbar spinal junction, and the extramedullary space of multiple segments grew along the spinal longitudinal axis; bleeding mass was revealed in MRI imaging; meninges, nerve root, and sacral canal metastases occurred.

The gold standard for the definitive diagnosis of AT/RT is biopsy combined with immunohistochemistry. The loss or inactivation of the SMARCB1/hSNF5/INI tumor suppressor gene has been identified as the hallmark genetic defect in RT. This mutation can arise somatically or more commonly inherited in the germline (> 35% of tumors). Loss of expression of this protein permitted the development of an immunohistochemistry assay that help make the clinical diagnosis of RT. RT are associated with a high rate of low birthweight and preterm birth, with a higher likelihood of later gestational age. A large number of multiple birth and twin pregnancy among case families with RT has been identified.

Histologically RT contains characteristic filamentous cytoplasmic inclusions, large nucleoli, and abundant eosinophilic cytoplasm. A variety of neural, epithelial, mesenchymal, or ependymal patterns may also be present. CNS RT comprise rhabdoid cells and areas of primitive neuroepithelial tissue resembling primitive neuroectodermal tumor. The cell of origin of RT is a primitive stem cell possibly derived from the neural crest.

Symptoms depend on the location of the tumor. Kidney tumors may cause a mass or swelling in the abdomen, while brain tumors can cause increased head size, developmental delays, or symptoms related to increased pressure in the brain. Diagnosis typically involves imaging studies like MRI or CT scans, followed by a biopsy to confirm the type of tumor. Brain and spine imaging studies should always be performed in newly diagnosed children with renal or extrarenal RT.

Management of RT include a combination of surgery, chemotherapy, and radiotherapy. The approach depends on the size, location, and extent of the tumor, as well as the age and overall health of the child. There are slight differences in management between COG, Dana Farber, and the European consortium mostly regarding induction chemotherapy and consolidation therapy. The early use of radiotherapy is controversial in young patients due to side effects of irradiating the spine.

The prognosis for selected patients, in particular those with localized RT associated with an older age and lower stage disease has improved somewhat, though the overall outcomes of RT remain poor despite maximized therapy intensity needing better targeted novel therapy largely focused on the biology of SMARCB1. RT has been found to be sensitive to the protein-translation inhibitor Homoharringtonine which could have a therapeutic potential.

PSU Volume 62 NO 05 MAY 2024

Alvarado Score

Acute appendicitis is the most common surgical emergency in children with ana estimated 6% lifetime event risk in the general population. More than 300,000 appendectomies are performed each year in the Unites States, and less than 10% result in the removal of a normal appendix. Appendicitis is thought to be caused by luminal obstruction from various etiologies, leading to increased mucus production and bacterial overgrowth resulting in wall tension, necrosis, and potential perforation.

The clinical diagnosis of appendicitis is based on symptoms, signs, and laboratory data. The differential diagnosis is extensive. Appendiceal perforation rates are higher in children and elderly patients. A variety of different approaches are recommended to decrease the negative appendectomy rate such as predictive scoring system, computer aided diagnosis, inflammatory markers, ultrasound, and CT scan.

The 2020 World Society of Emergency Surgery updated guidelines recommend the use of the Alvarado score to aid in the diagnosis of acute appendicitis in children, but it shows that the level of evidence is not high enough. The Alvarado score described in 1986 enables an early clinical diagnosis of acute appendicitis. The Alvarado score is a 10-point metric system composed of points for symptoms, clinical signs, and laboratory data.

For symptoms, there is 1 point each for migration of pain to right lower quadrant, anorexia, and nausea/vomiting. For clinical signs there are 2 points for tenderness in the right lower abdomen, 1 point for rebound tenderness, and 1 point for temperature greater than or equal to 37.3 C, and for laboratory data there are 2 points for leukocytosis and 1 point for neutrophils greater than or equal to 75%.

Once the score is reached, the total score is categorized as low (0-4), equivocal (4-6) and high (7-10) probability for acute appendicitis. With a low Alvarado score the child can be managed outpatient, with a score between 4 and 6 the child should undergo emergency department evaluation using initial ultrasound if available. Scores above 7 needs surgical consultation or imaging with serial evaluation.

The Alvarado score metric favor specificity over sensitivity, with high positive predictive value and diagnostic accuracy for acute appendicitis. In a recent meta-analysis studies involving 5985 children in 11 countries, the Alvarado score had a combined sensitivity of 76% and a combined specificity of 71% for the diagnosis of acute appendicitis in children. From the combined results the accuracy of the Alvarado score in diagnosing acute appendicitis in children still needs to be improved, and itÕs not recommended to be used alone.

The Alvarado score is practical, simple, and reproducible being a reliable tool in two pediatric situations: when imaging is scarce, and when a child with suspected appendicitis has difficulty finding the appendix on ultrasound due to obesity. Also, the use of the Alvarado score for diagnosing appendicitis can reduce radiation exposure examination in children to a certain extent by using it several times to evaluate the condition and observe the progression of the child condition. Alvarado score combined with C-reactive protein can improve the diagnostic accuracy of appendicitis and also help in the exclusion diagnosis.

The Pediatric appendicitis score includes similar clinical findings in addition to a sign more relevant in children: right lower quadrant pain with coughing, hopping or percussion. The appendicitis inflammatory response score includes fewer symptoms than the Alvarado score but adds an inflammatory biomarker, C-reactive protein, and allows for different severity levels of rebound pain, leukocytosis, CRP and polymorphonucleocytes. CT Scan continues to be the most commonly utilized imaging study in the evaluation of suspected appendicitis in approximately more than 75% of cases, though ultrasound is recommended as the initial modality especially in children and pregnant women.

Kaposi Sarcoma

In high-income countries, the annual incidence of new pediatric cancer is 15 cases per 100,000 children under the age of 15, with leukemia being the most common diagnosis. Children infected with human immunodeficiency virus (HIV) have a higher rate of malignancy when compared with children without HIV. Most children infected with HIV reside in sub-Saharan Africa. Children with HIV have an estimated 100-fold increased risk of developing Kaposi Sarcoma or Non-Hodgkin lymphoma.

Kaposi sarcoma (KS) is associated with co-infection with human herpesvirus-8 (HHV-8) and is the most common HIV-associated malignancy worldwide and the most frequently diagnosed cancer in many African nations. KS is an inflammatory neoplasm of endothelial cell origin, probably a polyclonal proliferation of spindle cell latently infected by human herpesvirus-8, which often evolves into an oligoclonal/monoclonal disorder. Four epidemiological forms of KS exist: 1) Classic, affecting elderly men, 2) Endemic, affecting young adults with a rapidly lymphadenopathic course, 3) Epidemic KS in HIV-infected patients being the most common form of pediatric KS worldwide, and 4) Iatrogenic KS in medically immunosuppressed patients affecting the skin, mucosa, lymphatic system, and visceral organs. Herpesvirus-8 is the causative agent for all epidemiological forms of KS in all patients. Pediatric classic and iatrogenic KS are extremely rare.

Biopsy of the KS lesion is required for definitive diagnosis. Histologic features include spindle-shaped cells, inflammatory infiltrates, and angioproliferation with erythrocyte extravasation. KS is staged according to the classification developed by the AIDS Clinical trials group Oncology Committee which stratifies patients based on tumor burden, immune status, and presence of any systemic symptoms.

The main feature that differentiates the childhood form of KS from adult disease is clinical presentation with primarily bulging lymphadenopathy. The Lilongwe Pediatric KS Staging Classification stratifies four distinct groups based on clinical phenotype: 1) mild/moderate disease limited to cutaneous and oral mucosal involvement, 2) lymphadenopathic disease, 3) woody edema, and 4) visceral and/or disseminated cutaneous/oral disease. The clinical course of KS in children with the epidemic form frequently follows a more aggressive course, without cutaneous involvement but involving mucosa and visceral organs. They are younger, with a mean age of 8 years. The endemic form is even younger (6 years of age) presenting with generalized or localized lymphadenopathy with sparse mucosal or skin lesions. Pediatric patients with classic KS present with more rapidly progressive disseminated and aggressive cutaneous lesions, oftentimes with mucosal and lymph node involvement, and can be lethal within 1-2 years of presentation. The iatrogenic form of KS is of variable age depending on the time of immunosuppressive therapy post-transplantation, presenting with pancytopenia and lymphadenopathy to more widespread visceral or mucocutaneous-cutaneous involvement.

For children with epidemic or iatrogenic KS, the most effective treatment requires correcting the underlying immunodeficiency. Treatment for endemic and classic forms of KS is targeted on the basis of localized or disseminated disease. Symptomatic localized lesions are oftentimes managed with local measures such as intralesional vinblastine, liquid nitrogen, laser therapy, localized radiotherapy, topical retinoic acid, or surgical resection. Multifocal, symptomatic, or disseminated disease is managed with systemic chemotherapy. Antiviral therapy can be considered for the prevention of (primary) HHV-8 infection and subsequent KS development with systemic chemotherapy.

The prognosis of epidemic KS has greatly improved with the use of highly active anti-retroviral therapy (cART). Immunosuppression from HIV infection and transplantation is associated with higher mortality risks. Positive outcomes in pediatric KS have been achieved in cohorts treated with chemotherapy and cART. Long-term survival is possible for pediatric KS in low-resource settings.

Embryonal Carcinoma

Embryonal carcinoma (EC) is a relatively rare type of nonseminomatous germ cell tumor that usually occurs in the ovaries and testes. EC is a malignant tumor that can be aggressive and spread to other parts of the body.

In males, the main presenting symptom of EC is a palpable testicular mass or asymmetric testicular enlargement. The tumor can also present with signs and symptoms associated with the presence of metastatic disease such as low back pain, dyspnea, cough, hemoptysis, hematemesis, and neurologic symptoms. The male counterpart of EC has a normal level of alpha fetoprotein (AFP). If elevated, the tumor suggests more of a mixed germ cell tumor, with the elevation of alpha fetoprotein produced by the yolk sac component. The average age at diagnosis is 31 years and typically presents with a painful testicular mass. Almost two-thirds of cases have metastasis at diagnosis. Testicular EC occurs mostly (84%) as a component of a mixed germ cell tumor, with only 16% being pure.

In females, EC is quite rare, accounting for 3% of all ovarian germ cell tumors. The median age at diagnosis is fifteen years. Symptoms and signs might vary and may include sexual precocity and abnormal uterine bleeding. Alpha fetoprotein and human chorionic gonadotropin (HCG) might be elevated. Children develop large unilateral tumors with a median diameter of 17 centimeters. Metastasis is present in 40% of cases upon diagnosis. Clinically, females present with abdominal pain, abdominal distension, or a pelvic mass.

In both males and females, imaging with US, CT-Scan, and MRI is needed, including a metastatic workup of chest and CNS.

EC can also arise in extragonadal sites such as the retroperitoneum, mediastinum, central nervous system, liver, and gastrointestinal tract. Primary intracranial embryonal carcinoma is a rare brain tumor. EC accounts for 5% of all intracranial tumors. Eighty percent of these tumors tend to occur along the midline, such as the pineal, suprasellar region, hypothalamus, and third ventricle. Preoperative imaging examination, blood serum, and cerebrospinal fluid levels of AFP and HCG can support the diagnosis. Subtotal to total removal with good preservation of important structures can be achieved in this tumor resection. EC has a poor prognosis in the CNS.

Pathologically, EC is a poorly defined tumor with associated hemorrhage and necrosis. Microscopic features include indistinct cell borders, variable architecture, balls of cells surrounded by empty space on three sides, nuclear overlap, and necrosis. Solid (55%), glandular (17%), and papillary (11%) are the most common primary patterns.

Initial management of EC is surgical excision, meaning radical orchiectomy through an inguinal approach in males and unilateral adnexectomy in females. In stage 1 disease, it is the curative treatment in 75% of all cases. The patient should be counseled for a possible biopsy of the contralateral adnexa when appropriate.

Non-seminomatous germ cell tumors are the most sensitive testicular and ovarian cancers to cisplatin-based chemotherapy. From three to four to six cycles of chemotherapy with BEP (bleomycin, etoposide, and cisplatin) is regarded as the gold-standard regimen for the treatment of germ cell tumors at all stages of disease. After completion of chemotherapy, tumor markers are repeated to see the decline in values, along with a contrast-enhanced CT scan to evaluate for any residual mass. Retroperitoneal lymph node dissection with adjuvant chemotherapy is the mainstay of managing low-stage non-seminomatous germ cell tumors in the United States.

Overall, fertility is reduced by an average of 30% after chemotherapy treatment. Fertility preservation in females is of utmost importance, including cryopreservation of oocytes, ovarian tissue, or embryos. A question in issue is how long after chemotherapy could women conceive. Six months is the time needed for human oocyte maturation from a dormant state to fully mature. Cancer patients are advised not to conceive until six months from the completion of chemotherapy. Many studies suggest that the right time is 24 months after the end of the last cycle of chemotherapy.