PSU Volume 56 NO 01 JANUARY 2021

Central Venous Catheter Tip Placement

Central venous catheters (CVC) are essential for providing long-term chemotherapy for cancer, total parenteral nutrition, central venous pressure monitoring, secure regular blood sampling, and prolonged intravenous management in children. Using ultrasound and Seldinger technique, the internal jugular, external jugular, cephalic or subclavian vein are usually cannulated as entrance points. The anatomic position of the tip of the CVC is of  upmost importance to avoid dysrhythmias, thrombosis, valvular insufficiency, inaccurate venous pressure monitoring, tricuspid valve damage, and perforation of the right atrium (RA), right ventricle or superior vena cava (SVC) resulting in cardiac tamponade. Tips located outside the heart are associated with thrombosis of the cava or its tributaries, inadvertent infusion into nontarget vessels, catheter dysfunction, erosion of the catheter into the lung or bronchus and risk of perforation with hemothorax. Catheter angulation, curvature or looping is a major risk for perforation. The recommended position of the tip of the CVC is just above the superior vena cava-right atrial junction parallel to the SVC  to prevent serious complications. Radiographic and fluoroscopy methods are the standard for defining tip position follow very closely by ultrasound and EKG. Several radiographic landmarks have been used to determine the exact position of the tip of the catheter in the SVC-RA junction. These include the right tracheobronchial angle and the carina. The right tracheobronchial angle has less clinical applicability as radiologist find difficult to identify in some chest films. The carina has several advantages as radiologic landmark of the catheter tip: it does not move with pathologic changes in the lung, it is positioned in the center of the body and it can be identified easily even in poor quality chest films. In adolescent and young adults a point approximately two vertebral body units below the carina was found as the landmark of the cavoatrial junction. In order to place the catheter tip at the level of the carina several external landmarks must be used to cut the proper length of catheter during insertion. The CVC tip can be reliably placed near the carina level using the external landmarks of the sternal head of the right clavicle and a perpendicular line connecting both nipples. The catheter distance should be measured from the insertion point to midpoint the distance between these two landmarks substrated by 0.5 cm and cut. The insertion depth is determined placing the CVC over the sterilized skin from the insertion point to the midpoint of the perpendicular line joining the sternal head of the right clavicle and the line connecting both nipples. Alternatively, the depth of insertion of the catheter can be determined by the distance from the skin puncture to the second intercostal space (sternal angle of Lewis). The length of the CVC using either the carina or SVC-RA junction as measured by thoracic CT-Scan correlates with the patient age and body surface area and formulas for each catheter length have been devised previously. The carina is still an easily sighted and clear radiological landmark in children to confirm that the CVC tip is outside the pericardial reflection. In neonates the carina is not always located above the pericardium, therefore, the carina could not be an appropriate landmark for CVC placement. In all cases, a chest film is mandatory after CVC placement to determine tip position and associated complications of punctured.

Bilateral Papillary Thyroid Carcinoma

Of all thyroid cancers occurring in the USA, around 10% occurs during the pediatric age. Almost 20% of all solid thyroid nodules in children harbor a malignancy. The most common histological type of thyroid malignancy found in children is papillary carcinoma, which together with the less common follicular variety (< 5%) comprise most cases of differentiated thyroid cancer in children. Differentiated thyroid carcinoma arises from the thyroid follicular cells. Papillary thyroid carcinoma (PTC) in children is characterized by a high incidence of regional lymph node metastasis at the time of diagnosis (60%), along with a higher incidence of bilateral and multifocal disease (30% and 65% respectively. In spite of this, children are less likely to die from disease, with disease-specific mortality less than 3%. The three most common risk factors identified in children with PTC include exposure to ionizing radiation in the head and neck area, a family history of thyroid cancer and a preoperative diagnosis of Hashimoto thyroiditis. A variety of genetic disorders may predispose to PTC including familial adenomatoid-polyposis, Carney complex, Werner syndrome, DICER1 syndrome and hamartoma tumor syndrome. The presence of lateral neck lymph node metastasis noted in preoperative ultrasound studies is associated with an increase risk of detectable bilateral PTC. FNA should be performed on any suspicious lymph nodes in the lateral neck as confirmation of metastatic involvement prior to lateral neck dissection. Of children diagnosed preoperatively with unilateral disease, if the dominant tumor measured greater than 2 cm a postoperative diagnosis of bilateral disease is more likely. Children with occult bilateral disease are more likely to have positive central compartment lymph node involvement, extranodal extension of disease, extrathyroidal extension, lymphovascular invasion and multifocal disease. Diffuse-sclerosing variant tumors is associated with an increase of bilateral disease. Total thyroidectomy maximizes disease-free survival, overall survival and quality-adjusted life expectancy in children with PTC compared with lobectomy. Almost one-fourth of children have occult contralateral disease with a high risk for persistent disease if a total thyroidectomy is not performed at the time of diagnosis. Lesser thyroid resection than total thyroidectomy is associated with as high as 10-fold greater recurrences rates. Inadequate lymph node dissections in patients with clinically positive nodes increase the need for subsequent intervention 3-fold. Addition of central lymph node dissection to total thyroidectomy in PTC decrease recurrence rate to less than 5%at ten years.     

Zenker Diverticulum

Zenker diverticulum is considered the most common diverticulum of the esophagus. It is usually seen in the 6th to 8th decade of life with only a few cases described in the pediatric age. Zenker diverticulum is a protrusion of pharyngo-esophageal mucosa through a weak zone in the posterior wall of the pharynx known as Killian's triangle. It is an acquired hernia of the posterior pharyngeal mucosa membrane at the pharyngo-esophageal junction occurring between fibers of the lower pharyngeal constrictor  and crico-pharyngeal muscles. Dysfunction of the cricopharyngeal muscle plays a major role in the pathogenesis of the diverticulum. It is a pulsion pseudodiverticulum since is associated with high intraluminal pressure and does not contain all the layers of the esophagus. Being a pseudodiverticulum there is involvement of only the mucosal layer. They are more common in males and present more frequently on the left side. Zenker diverticulum causes dysphagia, a sensation of food sticking in the throat, noisy deglutition, regurgitation of undigested food, cough, aspiration, chronic foreign body impaction and halitosis. Over time patients may present weight loss due to chronic dysphagia. Esophagogram (barium swallow is the gold standard), US or CT-Scan with oral contrast of the neck and proximal thorax are diagnostic, revealing a diverticular pouch filled with air, debris and food particles compressing the trachea. Zenker diverticulum is classified by their longitudinal size into small (diameter less than 2 cm), medium (diameter 2-4 cm), and large (diameter > 4 cm). Zenker diverticulum is associated with Marfan syndrome due to the abnormal weak wall related to the connective tissue disorder. The differential diagnosis includes a congenital crico-pharyngeal diverticulum, duplication of the esophagus, traction diverticulum, a false diverticulum above a congenital stenosis, traumatic pseudodiverticulum of the pharynx in newborns (perforation by nasogastric tube), and a postoperative diverticulum after repair of tracheo-esophageal fistula. Management of a Zenker diverticulum depends on the location, symptoms and size of the diverticulum. Endoscopy stapling or laser resection, diverticulectomy, cricopharyngeal myotomy or diverticulopexy are several procedures performed for Zenker diverticulum. Myotomy is the mainstay of treatment with favorable outcomes in more than 80% of patients with a reduced recurrence rate. Endoscopic management is not recommended in large diverticula because of incomplete emptying of pouch remnants.     

PSU Volume 56 NO 02 FEBRUARY 2021

Congenital Short Bowel Syndrome

Short bowel syndrome is a clinical disorder characterized by diarrhea, malabsorption and needs of parenteral nutrition for life support. In newborns, short bowel syndrome is most commonly an acquired disorder after surgical bowel resection due to conditions such as necrotizing enterocolitis, gastroschisis, volvulus, extensive aganglionosis in Hirschsprung's disease, or intestinal atresia. Born with a short bowel known as congenital short bowel syndrome (CSBS) is a very rare condition in newborns associated with a high mortality rate and prognosis. According to autopsy reports, the length of the  small intestine as measured from Treitz to ileocecal valve correlates with crown-to-heel length. The mean length of the small bowel in full term infants is approximately 240 cm and increases to 600 cm in adulthood. Short bowel syndrome manifests in newborns when the small bowel length is less than 75 cm. Newborns with CSBS can be as short as 20 cm in length, with a mean length of 50 cm. The pathogenesis of CSBS is poorly understood. CSBS occurs most often in association with malrotation (> 96%). The normal elongation, rotation and herniation of the small bowel is interrupted or delayed due to lack of space between the developing digestive tube and umbilical celom. Other believe is a defective neuroenteric development since intestinal dysmotility is an important component of the syndrome. Children born with CSBS have a loss of function nonsense mutation in the CLMP (Coxsackie- and adenovirus receptor-like membrane protein). CLMP encodes a tight-junction membrane protein of the bowel, located in chromosome 11, and expressed during embryonic development. Mutations in CLMP cause a recessive form of CSBS. In other patients a mutation in FLNA gene was found in chromosome X, which encodes for a cytoskeletal protein called filamin A that binds to actin. Other congenital anomalies associated with CSBS include pyloric stenosis, appendiceal agenesis, acheiria, dextrocardia, hemivertebrae and paten ductus arteriosus. Clinically, most babies with CSBS develop bilious vomiting, diarrhea, failure to thrive with signs/symptoms consistent with intestinal obstruction. Onset of intestinal volvulus associated with acute mesenteric ischemia is rare in these patients since a short bowel length precludes twisting. CSBS is diagnosed by barium-contrast studies and confirmed by exploratory laparotomy. Management of CSBS consist of parenteral nutrition with early introduction of enteral nutrition. In the event of failed adaptation and liver failure with reduced venous access from treatment, transplantation becomes the hope for these children. Survival beyond the first year with CSBS is 75% and improving. Most common cause of death is sepsis.     

Biliary Dyskinesia

Biliary Dyskinesia (BD) is characterized by an abnormal gallbladder contractility identified using cholecystokinin-stimulated hepatobiliary iminodiacetic acid (HIDA) nuclear scans. BD is a diagnosis of exclusion so other causes such as irritable bowel syndrome, dyspepsia, GE reflux disease needs to be rule out. The diagnosis is established when the gallbladder has an ejection fraction less than 35% and the child has typical symptoms of biliary colic without gallstones. Gallbladder dyskinesia is becoming the most common indication for gallbladder removal in adults and pediatric population. The most accepted pathogenesis of BD is uncoordinated contractions and relaxation of both the gallbladder and sphincter of Oddi. Subsequent distension of the gallbladder leads to inflammation, hypersensitivity and dysfunction. 75% of affected cases are females,  most cases are white adolescents and almost 50% are obese. Major preoperative symptoms in children with BD include nonspecific vague chronic right upper quadrant/epigastric abdominal pain, nausea, postprandial pain, fatty food intolerance, vomiting, constipation and diarrhea in this order of frequency. Children with symptoms and BD undergo a series of preoperative studies without significant pathologic findings such as US, CT-Scan, MRI, UGIS and upper/lower GI endoscopy. Most of this cases are referred by pediatric gastroenterologist after trying several medical management options. Initially more than 80% claim pain improvement after cholecystectomy, but two years or more after surgery 30-40% continue with similar symptoms. The difference between short and long-term results may be due to true recurrence of symptoms or inaccurate reporting by parents who wants to please the surgeon. Two-third of gallbladders removed due to BD shows chronic cholecystitis. Patients with chronic inflammation are more likely to persist with symptoms at long-term follow-up. An ejection fraction below 15% is usually associated with a higher resolution of symptoms after cholecystectomy. BMI percent, pain during CCK administration during the HIDA scan and presence of chronic cholecystitis does not predict which patient will have short or long-term improvement in symptoms. Factors independently associated with short term pain improvement after cholecystectomy includes shorter duration of pain before surgery, history of vomiting preop, no history of fevers or obstructive sleep apnea. Factors independently associated with short-term complete symptoms, resolution includes history of epigastric pain and lower GI disease. Longer duration of symptoms predicts poor outcome after cholecystectomy in BD. Symptoms of functional dyspepsia overlap with symptoms of BD in children. There is no well-defined nonsurgical management of BD. Some researchers advocate medical over surgical management of BD since BD is not a life threatening condition, there are no serious complications and some children continue to experience symptoms after cholecystectomy. With persistent abdominal pain after cholecystectomy there is a high index of suspicion for sphincter of Oddi dysfunction. Studies comparing cholecystectomy to nonsurgical medical management show same results in both groups.       

Pancreatic Cyst Fluid Analysis

The extensive use of ultrasound has uncovered symptomatically as well as asymptomatic pancreatic cysts. The majority of pancreatic cysts are found incidentally when abdominal imaging is performed for other indications. Pancreatic cysts can either be simple (retention) cysts, pseudocysts and cystic neoplasm. Cystic neoplasms are further subdivided into serous cystadenomas, mucinous cystic neoplasms, intraductal papillary mucinous neoplasms or papillary cystic neoplasms. The majority of pancreatic cystic lesions identified are mucinous cystic neoplasms. Since some of these pancreatic cysts can develop into malignancy, a diagnosis performing aspiration and analysis of the cyst fluid must be undertaken. Accurate diagnosis leads to effective and standard management. This can be achieved using either US- or CT-guided percutaneous aspiration or endoscopic ultrasound fine needle aspiration. The diagnostic accuracy after aspiration is very high (~95%). The fluid is analyzed for cytology, viscosity, extracellular mucin, tumor markers (CEA, CA 19-9, CA 15-3, CA 72-4, CA 125), enzymes (amylase/lipase) and DNA quality/content or mutational analysis. Mutational analysis can further characterize allelic imbalances, loss of heterozygosity (LOH) and K-ras mutation. Estimates of the cyst fluid volume can be approximated using the formula 4r3; where r is the radius of the cyst. Imaging is the less accurate in the diagnosis of pancreatic cystic lesions. Surgical resection is recommended if a cyst has both a solid component and dilated main pancreatic duct. Viscosity is lower in pseudocysts (1.3) and serous cystadenomas (1.27), compared with mucinous cystadenoma (1.84) and mucinous cystadenocarcinomas (1.90). CEA levels are high in mucinous cystadenomas and very high in mucinous cystadenocarcinomas when compared with pseudocysts and serous cystadenomas. Elevated CEA and viscosity accurately predict mucinous cysts. The presence of extracellular mucin is predictive of a mucinous neoplasm. Cytological identification of extracellular mucin and CEA elevation are predictors of mucinous neoplasm and malignancy. Cytology detects mucin containing cells, malignant cells, glycogen-rich cuboidal cells, branching papillae and abundant enucleate squamous cells and debris. Cytology is diagnostic in less than 60% of pancreatic cysts. CA19-9 cyst fluid levels above 50,000 U/ml are found in mucinous cystadenoma and cystadenocarcinomas. Levels below 37 U/ml suggest serous cystadenomas or pseudocysts. CA 19-9 is suitable for detection of malignancy but is insensitive for premalignant lesions. CA72-4 cyst fluid levels above 40 U/ml are significantly high in mucinous cystic tumors. CEA levels greater than 400 ng/ml are characteristic of mucinous tumors and cystadenocarcinoma, while CEA levels less than 4 ng/ml are associated with serous cystadenomas. Cyst fluid CEA is the most accurate test available for diagnosis of mucinous cystic lesions of the pancreas with a cut off value of 192 ng/ml for diagnosis. In some centers CEA is the only tumor marker routinely use for diagnostic work-up. Amylase/lipase high levels (above 250 U/L) are commonly seen in pseudocysts. Cyst fluid amylase is of limited utility in evaluation of pancreatic cysts. Low values are associated with a neoplastic tumor. DNA analysis has found that a K-ras mutation followed by allelic loss is most predictive of malignancy in a pancreatic cyst. In malignant cysts, elevated CEA is more predictive of histology than K-ras or LOH mutations. DNA mutational analysis should be used selectively rather than routinely. Costs are significant with DNA analysis. Confocal laser endomicroscopy (CLE) is a novel technology for real time in vivo microscopic imaging using a probe inserted through a 19-G needle. CLE findings of mucinous tumors include finger-like papillae with layers of a thick band-like epithelium. Serous cysts have a superficial network or fern-type pattern, while pseudocysts contain bright particles. Cytology, CEA levels and -K-ras mutation analyses are the most important in clinical practice. Is important differentiate between benign and malignant lesions to determine whether surgical resection or conservative management is required. (See attached Table).

PSU Volume 56 NO 03 MARCH 2021

Complicated Appendicitis: How much antibiotics?

Appendicitis is the most common acute surgical emergency in children. Though medical management of appendicitis using parenteral antibiotics has gained popularity, laparoscopic or open appendectomy is still the standard of care. The basic tents of management of appendicitis are: resuscitate children with systemic inflammatory response syndrome, control the source of contamination, remove most of the infected or necrotic material and administer antimicrobial agents to eradicate residual pathogens. Appendicitis can be classified as simple or complicated. Complicated appendicitis refers to histologic changes in the appendix associated with either gangrene and/or perforation. Perforated appendicitis occurs in approximately 25-30% of children presenting with acute appendicitis. Traditionally, complicated appendicitis is managed postoperatively with 7-14 days of antibiotics. This long therapeutic regimen has been challenged periodically. The main reasons for postoperative antibiotics after appendectomy in complicated  appendicitis is reducing the incidence of surgical site (wound) infection and formation of intraabdominal fluid collections (abscess). Excluding gangrenous appendicitis, wound and intraabdominal infection rates for children with perforated appendicitis are 4% and 8% respectively. With the standard use of laparoscopy with smaller incisions for appendectomy the surgical site infection rate has decreased considerably. All children undergoing appendectomy should receive a preoperative dose of a broad-spectrum antibiotics before surgery. Cases with simple appendicitis or normal appendix do not need to receive postoperative antibiotics as postoperative infectious complications are extremely rare in this group after a single preoperative dose of antibiotics. Complicated appendicitis can be managed with shorter course of three to 5 days of postoperative antibiotics after adequate source control. This course depends on the clinical response of the child. In synthesis, the parameters utilized to evaluate the clinical response to postoperative antibiotic therapy include: temperature, heart rate, WBC count, and gastrointestinal dysfunction due to peritonitis. This means that until fever subsides (T < 38.5 C), normal heart rate returns, WBC < 11 and resolution of ileus with oral intake is not achieved, the child will need antimicrobial therapy. The STOP-IT trial found that outcomes in patients with intraabdominal infections who undergo successful source control procedure and received a fixed 4 days course of antimicrobial therapy had similar results in outcome as patient whom systemic antimicrobial agents were administered until after resolution of signs and symptoms of sepsis. The occurrence of a postoperative abscess is the single most important determinant of outcomes in children with perforated appendicitis. Retained fecalith after appendectomy are a source of continued and recurrent infection and should be removed surgically. As we define better grades of perforation during surgery, we will be able to correlate them with increased postoperative abscess rate.    

Intraoperative Cholangiogram

Cholelithiasis has increased in incidence in the pediatric population, mostly the result of western diet and improve ability to detect them using ultrasonography. Cholelithiasis can cause biliary colicky pain, acute and chronic inflammation, pancreatitis and biliary obstruction from gallstone impaction in the common bile duct (choledocholithiasis). Hemolytic disorders account for 20% of children with cholelithiasis. Laparoscopic cholecystectomy (LC) is the gold standard method for gallbladder removal in children and adults with disease gallbladder. In children with gallstone pancreatitis, biochemical jaundice, cholangitis or ultrasound evidence of bile duct dilatation an MRCP should be performed to diagnosed choledocholithiasis before embarking in removal of the gallbladder. Laparoscopic removal of the gallbladder with bile duct obstruction could result in leakage of the cystic duct stump or development of cholangitis. In the laparoscopic era, ERCP with sphincterotomy is used either before LC for suspected common bile duct (CBD) stones or after LC for missed CBD stones, bile duct injuries or late strictures. Intraoperative cholangiogram (IOC) is a technique in which a small catheter is passed either through the cystic duct or infundibulum of the gallbladder, contrast is injected and fluoroscopic films of the biliary tree are obtained. IOC was first reported in the early 1990's. Previous indications for IOC include findings of bile duct dilatation, defining aberrant biliary tree anatomy, in cases of confused anatomy, confounding biliary disorders (choledochal cysts, biliary atresia or other congenital anomalies), and when bile duct injury is suspected during cholecystectomy. In places where MRCP is not available, IOC is useful to identify biliary anomalies or obstruction causing choledocholithiasis, cholangitis, elevated liver enzymes or pancreatitis. With time, IOC has gone from a routine procedure to a selective procedure during removal of the gallbladder in children. IOC adds time to the procedure potentially increasing costs, puts the patient at risk of iatrogenic injury, adds radiation exposure to the patient, and is no more sensitive than preoperative MRCP. Recent nationwide database studies of cholecyctectomies in children have found that:1)  Routine IOC is more commonly employed in children with cholecystitis and less commonly performed in patents with cholelithiasis. 2) Cholecystectomy alone when compared against cholecystectomy with routine IOC is associated with higher rates of bile duct injury, perforation, laceration, sepsis and other infections. 3) These children are less likely to have readmission to the hospital within 30 days and one year. 4) Patients who undergo routine IOC have decreased hospital length of stay and decreased overall index hospital costs. Other studies have found IOC and hospital operative volume are not readily associated with decreased bile duct injury. Increase use of IOC or tendency is associated with increased risk for bile duct injury. The use of IOC is associated with surgeons' preference and training as there is no clear evidence to guide routine utilization.      

Appendicitis during Covid19 Pandemic

Acute appendicitis is the most common surgical emergency in children. More than 70,000 appendectomies are performed in children each year in the USA, approximately one-third of childhood admissions for abdominal pain. Since the discovery of Sars-Cov2 coronavirus as the cause of Covid19 disease early in 2020, a global pandemic developed which continues to affect medical and surgical care of children and adults. Children who develop Covid19 mostly suffer from a mild disease process, only a minority presenting with respiratory distress syndrome or multiorgan failure. With the pandemic the instructions to the population were to stay home, avoid visiting local clinics and hospitals while using more telemedicine-based practice. In many institutions programmed or elective surgery was postponed. Parental concerned with the possibility of contracting Covid19 in public places such as clinics or emergency rooms couple with inadequate clinical evaluation using telemedicine, and the inability to perform a full physical examination led to a delayed diagnosis of appendicitis. This resulted in an increase in development of complex appendicitis (gangrenous and perforated) along with an increase in intraabdominal complications such as perforation and peritonitis with peri-appendicular abscess formation. An increased reliance on outpatient care during a time when many clinics were not seeing patients most likely contributed to delay in diagnosis. As hospital systems were reaching capacity, a delay in presentation was created due to the need for transfer from one health care center to another. A few institutions changed to non-operative management of appendicitis in an effort to conserve resources, minimized non-emergent surgical procedures and allow for Covid19 testing to result. Non-operative management with intravenous antibiotics can be applied to almost 50% of children presenting with acute appendicitis. Children with persistent pain, leukocytosis or an appendicolith in images were taken directly to the operating room for laparoscopic appendectomy. The observed increase in complicated appendicitis cases in children during 2020 is most likely due to Covid19 pandemic. In other institutions the covid19 pandemic increased the number of children managed for acute appendicitis during the lock down due to closure of general surgery departments in proximity hospital resulting in an increase in referral to children hospitals. Children managed for acute appendicitis were older than historic controls and more commonly transferred from other institutions. Nonoperative management of uncomplicated appendicitis in children resulted in an increase in length of stay and readmission. Ages at presentation correlated with increased severity of disease on presentation and higher rates of perforation and intraabdominal abscess formation, increased use of antibiotics, longer length of stay and longer duration until symptoms resolution for children managed during the pandemic. Children with appendicitis presented during the pandemic with more advanced disease.      

PSU Volume 56 NO 04 APRIL 2021

Abdominal Wall Defects and Undescended Testis

The most common congenital abdominal wall defects (AWD) in children affecting testicular descent include gastroschisis, omphalocele and prune belly syndrome. Gastroschisis is  more common than omphalocele or prune belly syndrome. Undescended testes are more common among AWD patients than the general population, with the highest prevalence in omphalocele. Testicular descent is known to be related to intraabdominal pressure and the gubernaculum. Without higher pressures the forces that encourage testicle migration are absent. Failure of appropriated abdominal pressure and/or sudden disruption of the gubernaculum at the time of formation can lead to abdominal undescended testes. Undescended testes are a concomitant birth anomaly associated with abdominal wall defects in almost 20 to 40% of all males patients. Undescended testes in children with abdominal wall defects may be found within or outside the abdominal cavity. The majority of undescended testes are found at the internal spermatic ring. Gestational age and birth weight do not appear to be a significant factor associated with testicular maldescent in several series. Closure of the abdominal wall defect using either mesh or primary closure is initially warranted. After closure of the abdominal wall defect and in the ensuing next 12 months, more than half of all undescended testes migrate to the appropriate position at follow-up requiring no intervention. Migration of the testes into the scrotum in cases of left-sided undescended testes born with gastroschisis, along with most in omphalocele is less likely. Of the testes that do not spontaneously descend into the scrotum, nearly half (43%) migrated into the inguinal canal. In cases where the testes remained in the abdominal cavity (non-palpable), laparoscopy is successfully performed to localize and remove or reposition the testes. Early conservative management allows normal spontaneous descent in most testes. Testes that are extraabdominal at birth appear to be less likely to spontaneously migrate into the scrotum compared with those that are intraabdominal at birth. Extraabdominal testes seem to have a greater incidence of atrophy and need for orchiectomy. Babies with prolapse testes out of the abdominal cavity should undergo manual repositioning placing the testis as near as possible to the internal spermatic ring. It is important to record the position of the intraabdominal undescended testes at the time of abdominal wall repair because future diagnostic laparoscopy or exploration is likely to be difficult. The majority will descend on their own without any need for surgical intervention. Orchiopexy in a newborn with fragile testicular vessels and the risk of compromised blood flow in the presence of temporarily raised intracoelomic pressure after primary closure may jeopardize testicular viability. Other authors believe that early mobilization and fixation can improve the outcome of the undescended testis. Surgical intervention for an undescended testis after closure of AWD is challenging, characterized by adhesions and short gonadal vessels necessitating staging the descent.  

Congenital Anal Stenosis

Congenital anal stenosis is a rare disorder classified as a low anorectal malformation, mainly a short stenosis in most cases, but sometimes the child has a funnel shape long stenosis associated with a presacral mass, bony sacral defect, anterior meningocele or other anomaly. The type of sacral dysplasia is scimitar and the presacral tumor is a mature teratoma in most of the cases. Children with congenital anal stenosis suffer from chronic intractable constipation, soiling, encopresis and megarectosigmoid. Constipation is the most common early functional problem in children with anal stenosis in more than 40% of the cases. Recalcitrant constipation is more common in children with a delayed diagnosis and treatment of anal stenosis. Congenital anal stenosis (CAS) can also be associated with Mayer-Rokitansky-Kuster-Hauser syndrome. On physical examination, children with CAS have a stenotic opening at the normal anal site barely admitting a small Hegar dilator. Palpable fecalomas can be found upon abdominal examination. In this malformation, the anal canal is usually located at least partially inside the voluntary sphincter funnel. Occasionally the diagnosis of anal stenosis is delayed to later infancy, especially in cases where the bowel outlet is stenotic but at or near the proper anal position. Newborns with anal stenosis usually pass meconium in the first 48 hours after birth. Children born with CAS should undergo an active search for associated malformations including echocardiogram, ultrasound of the spinal cord and kidneys, cystourethrogram and imaging of the entire spine including the sacrum (MRI). CAS can be managed with gradual Hegar dilatations usually without the need for anesthesia. Serial dilatations are started with a Hegar dilator that is easily fitted into the anal opening, usually with a size between six and 8 mm. Dilatations are taught to parents to continue management increasing to the next number on a weekly basis, continued for six weeks after the age-appropriate size of the anus is reached. Currarino syndrome, dysganglionosis including Hirschsprung's disease and chromosomal defects commonly occurs in children with funnel anus. The mortality of patients with low anomaly as CAS, is about three times lower than that of patients with high anomalies, and usually associated to cardiac defects. Long-term results of low malformations are usually good in most patients. Poor results are usually associated to neurological damage, mental retardation or insufficient care of patients. In severe cases of anal stenosis, the posterior rectum is mobilized in the form of rectal advancement, and the posterior 180 degrees is anastomosed directly to the skin with preservation of the anal canal as the anterior final anoplasty. These patients have an excellent prognosis for bowel control and fecal continence, and therefore, complete mobilization and resection of the anal canal must be avoided. Those children with CAS and stenosis involving only the skin-level can be managed with a Heineke-Mikulicz anoplasty with very good results.

Appendix Duplication

The vermiform appendix is a tubular, narrow, worm-shaped part of the alimentary canal that lies near the ileocecal junction and communicates with the cecum. The appendix develops as a conical extension from the apex of the cecal diverticulum which arises from the antimesenteric border of the proximal part of the post arterial segment of the midgut. Anomalies associated with the appendix are rare. Duplication of the vermiform appendix is very rare occurring with an incidence of 0.0004% after appendectomy. Appendiceal duplication is classified into three types (Cave-Wallbridge classification). Type A consists of various degrees of partial duplication on a normally localized appendix with a single cecum. Type B consists of a single cecum with two completely separate appendixes. This type is further subdivided into a B1, bird-like type if the two appendixes are located symmetrical on either side of the cecum as usually occurs in birds, and B2 also known as tenia-coli type which has a normally located appendix arising from the cecum at the usual site and a second separate rudimentary appendix located along the line of one of the tenias. B1 or bird-like type of duplication is the most common type of appendiceal duplication (37%). Type B2 duplication can be mimicked by a solitary inflamed diverticulum found on the cecum, usually at the medial border just above the ileocecal junction. B3 if the second appendix is located along the tenia of the hepatic flexure of the colon, and B4 if the location of the second appendix is along the tenia of the splenic flexure of the colon. Type C consists of a duplicated cecum, each with an appendix. A horseshoe configuration of duplication and triple appendices have also been described. Appendiceal duplication is most commonly identified incidentally during surgery or at autopsies. The most common presentation is appendicitis with the duplication being discovered intraoperatively. Median age at presentation of these patients is adolescent years, males and females affected equally. CT-Scan is the best mode of imaging to identify a duplicated appendix.  Besides inflammation, appendiceal duplication can present with recurrent intussusception or an appendiceal mass. Surgeons have to be aware of such anomalies since a second laparotomy revealing a previously removed appendix can cause medicolegal situations. In cases with appendiceal duplication, when only one appendix is inflamed, both should be removed to avoid a diagnostic dilemma that may arise later.  

PSU Volume 56 No 05 MAY 2021

Eosinophilic Cholecystitis

Eosinophilic cholecystitis is described as acute acalculous cholecystitis associated with infiltrations of eosinophils into the gallbladder wall. Acalculous cholecystitis is a rare condition in children. It occurs during the course of infectious disease, as well as in children on total parenteral nutrition, after surgery, trauma and extensive burns. The etiology of acalculous cholecystitis includes decreased blood flow to the gallbladder, biliary tract obstruction and hyperconcentration of the bile. The disease can progress to necrosis or perforation of the gallbladder. Eosinophilic cholecystitis (EC) is very rare, reported in 0.5-6.5% of removed gallbladders. The etiology of eosinophilic cholecystitis is unknown and probably represents a hypersensitivity type of inflammatory response to altered bile. Histologic findings diagnostic of eosinophilic cholecystitis includes transmural infiltration of leukocytes with more than 90% eosinophils present. Known causes of eosinophilic cholecystitis include parasitic infestation (clonorchis sinensis, echinococcus and Ascaris lumbricoides), gallstones, allergies, reaction to certain medications (erythromycin, L-tryptophan and cephalosporins), allergic granulomatous vasculitis, and association with eosinophilic gastroenteritis and/or eosinophilic pancreatitis. Gallstones can be found in almost 90% of the eosinophilic cholecystitis cases. Eosinophilic cholecystitis is more common in adult females between the ages of 25-64 years. In children, most cases occur during teenage years, though patient as young as seven years of age has been reported. Symptoms of eosinophilic cholecystitis resembles those of acute cholecystitis, including pain in the upper right quadrant, fever, jaundice, Murphy positive sign, altered mental status, shock, leukocytosis and postprandial nausea and vomiting. Eosinophilic cholecystitis can be diagnosed only on resection of the gallbladder and histologic examination. The diagnosis can be suspected if there is evidence of peripheral eosinophilia which occurs in 10-15% of cases. Ultrasound of the abdomen shows features of calculus cholecystitis with pericholecystic fluid collection and edema, thickened gallbladder wall and dilated common bile duct. The treatment of choice of eosinophilic cholecystitis is removal of the sick gallbladder. Cases associated with eosinophilic gastroenteritis or cholangitis, can benefit from steroids medication as adjuvant therapy. Eosinophilic cholecystitis usually show a good prognosis and patients with cholecystitis alone improve after cholecystectomy.  

Ovarian Harvest

With the advent of newer therapeutic options and increase in intensity of such therapy more than 80% of children diagnosed with cancer will be long-term survivors. During management for cancer children will suffer long-term adverse effects such as loss of fertility. Treatment protocols highly deleterious for ovarian function include high dose alkylating agents (cyclophosphamide and busulfan), total body irradiation and abdominopelvic irradiation (5-20 Greys) that includes both ovaries. Ovarian damage is drug- and dose-dependent and increases with age at treatment. For prepubertal females, ovarian harvest using tissue cryopreservation is currently the only available means of potentially preserving gonad function and fertility. Ovarian tissue harvesting can take place immediately before intensive chemotherapy or irradiation. Ovarian tissue is collected during the removal of a primary abdominal tumor, or by means of a small suprapubic laparotomy or laparoscopy. A single ovary or 2/3 of each ovary  is removed for cryopreservation. Most cases of major bleeding requiring transfusion or re-operation are associated with partial oophorectomy. Since the ovary can be different in the number of follicles present, some people prefer specimen collection from both ovaries. During the surgical procedure it is also possible to move residual gonads in order to reduce effects of local therapy (ovarian transposition). The preserved ovary is frozen down to liquid nitrogen temperature. Using a biopsy of the cortex of the removed ovary the number of primordial and primary follicles per square mm is determined. Also, in all malignant cases small samples of gonadal tissue are also sent for routine pathological assessment to rule out any gonadal involvement by the primary cancer. Ovarian tissue is preserved until the child recovers and it is reimplanted. Primordial follicles can be isolated from cryopreserved ovarian tissue and grown to maturity in vitro to be utilized for in vitro fertilization and embryo transfer. Orthotropic sites of reimplantation are the residual ovary or a peritoneal pocket in the ovarian fossa that permit a spontaneous pregnancy which is not recommended in case of pelvic irradiation. Heterotrophic sites are the subcutaneous forearm or abdominal tissue. Ovarian tissue transplant, whether orthotopic or heterotopic, would allow for ovarian hormonal production and restoration of a normal hormonal milieu allowing future pregnancy. Orthotropic ovarian reimplantation has led to the birth of more than 130 healthy babies. Mature oocyte and embryo cryopreservation is an appropriate strategy for fertility preservation in postpubertal females. Oocytes can be collected by transvaginal oocyte pick up, from excised ovarian tissue or a combination of both procedures. However this approach is time consuming with a low pregnancy rate and does not replace ovarian tissue transplantation.

Minimally Invasive Follicular Thyroid Carcinoma

Papillary and follicular thyroid carcinomas are considered the two differentiated carcinomas arising from follicular cells most commonly found in children. Papillary thyroid carcinoma accounts for more than 95% of all cases. Follicular thyroid carcinoma (FTC) accounts for less than 5% of all cases, occur more commonly in females, and is characterized by capsular and vascular invasion precluding making a categorical diagnosis using fine needle aspiration (FNA) biopsy. FNA biopsy usually describes a follicular tumor and the child undergoes removal of the affected lobe with the tumor. FTC is known to be associated with TSH elevation, iodine deficiency areas, hemiagenesis and radiation exposure. Tumor size of pediatric FTC is significant larger than in adult FTC. Histology of pediatric FTC is classified into five patterns: microfollicular, follicular, solid/trabecular, oncocytic and mixed patterns. Microfollicular pattern is the most common, while solid/trabecular the most rare. In FTC, RAS mutation is the most common genetic alteration with a prevalence in children of 12%. RAS mutation is associated with smaller tumor size with a potential low risk behavior in children. Follicular thyroid carcinoma can be further divided into minimally invasive and widely invasive. Minimally invasive FTC is diagnosed histologically when microscopic penetration of the tumor capsule is found but there is no vascular invasion. Minimally invasive FTC is difficult to diagnose prior to thyroidectomy unless distant metastases to bone or lung and/or lymph nodes have been detected and diagnosed by FNA or further imaging. Definitive diagnosis is established after hemithyroidectomy. Minimally invasive FTC is an encapsulated neoplasm characterized by unequivocal capsular invasion with a relatively uneventful and indolent course. Minimally invasive FTC carries an excellent prognosis with low risk of recurrence or disease-specific mortality. Removal of the affected lobe and five-year ultrasound-guided observation is sufficient therapy. Widely invasive FTC is more aggressive, shows a widespread infiltration of blood vessels into the adjacent thyroid parenchyma, displaying a poorer prognosis than minimally invasive variant. Completion total thyroidectomy as a second surgery and radioactive iodine ablation is recommended for invasive FTC. Poor prognostic factors associated with follicular thyroid carcinoma include older age, distant and neck metastasis. Children with tumor exceeding 4 cm in length and associated with vascular invasion carries a poorer prognosis.    

PSU Volume 56 NO 06 JUNE 2021

Neurothekeoma

Soft tissue tumor lesions are uncommon in the pediatric age group. They differ from adults counterpart in frequency, anatomical site and prognosis. In children, a dermal nodule could represent a fibrous tumor, histiocytic tumor, lymphocytic tumor, melanocytic tumor or a tumor of neural origin. Neurothekeoma is a rare benign soft tissue tumor with distinctive histological features commonly located on the upper extremity or the head and neck region in children. Originally thought to arise from peripheral nerve sheath, it has been postulated that neurothekeomas are of fibrohistiocytic differentiation. Based on histology, immunohistochemical findings and amount of myxoid matrix present, three variants of neurothekeoma are described: 1) myxoid, which is the most common variety, 2) cellular and 3) mixed type. The classic myxoid type, is encapsulated, characterized by myxomatous changes, less cellularity with well-circumscribed spindle cells in a myxoid matrix associated with multinucleated giant cells. The cellular type is not encapsulated, the cells are epithelioid with eosinophilic cytoplasm and rare mitosis. Cellular neurothekeomas can be locally invasive with perineural and vascular invasion, but no locoregional metastasis. The mixed type of neurothekeoma has varied cellularity with focal myxoid regions. Clinically, neurothekeomas are slow-growing asymptomatic lesions, but may be accompanied by pain upon pressure. Though commonly dermal, mucosa and submucosal lesions have also been described. Neurothekeomas tend to affect females more often than males, usually in the second and early third decades of life. Age at presentation can be between 15 months and 84 years. The most common location is the upper extremity, followed by the head and neck region, and lower extremity. Neurothekeoma clinically presents as a superficially located skin-colored, pink, red, or brown well-circumscribed papule or nodule measuring less than 2 cm. Management of neurothekeomas consists of complete surgical excision with microscopic negative margins. Incomplete removal of the lesion will lead to recurrence in approximately 15% of patients. There are reports of multiple neurothekeomas presenting concurrently. It is almost impossible to make the diagnosis of a neurothekeoma preoperatively, unless the patient has suffered a previous excision of such dermal tumor. As neurothekeomas are considered benign lesions, the prognosis is excellent with very low recurrence rate following complete surgical excision.

Renal Medullary Carcinoma

Renal medullary carcinoma (RMC) is a rare and highly aggressive neoplasm that affects African-American adolescents and young adult occurring almost exclusively in children with sickle cell trait or sickle cell hemoglobinopathy. Sickle cell trait is a risk factor for several conditions including chronic kidney disease, RMC, venous embolism and sudden death. Most patients present between the ages of 11 and 39 years, with males affected 2:1 ratio. Most common presenting symptoms  for renal medullary carcinoma are gross hematuria, flank pain, weight loss and abdominal mass. RMC is characterized for early and widespread metastases. RMC arises from the renal papilla or calyceal epithelium triggered by chronic medullary hypoxia. Imaging of RMC commonly identifies a mass, more often in the right-side kidney, with an average size of 7 cm associated with satellite lesions and intratumoral necrosis. The most common imaging appearance of RMC is a poorly marginated, infiltrating mass abutting the pelvocaliceal system. This tumor is typically associated with a pseudocapsule with well-defined margins. Lung metastasis have an atypical imaging appearance with the most common pattern being pulmonary lymphangitic carcinomatosis and nodules with indistinct margins being more common than nodules with distinct margins. Pathologically, RMS is an infiltrative tumor extending from the renal pelvis. These tumors comprise sheets of poorly differentiated cells commonly found to have a reticular growth pattern and adenoid cystic component with an infiltrate of neutrophils. Visualization of sickle red blood cells is pathognomonic for RMC. Most RMC are associated with a loss of SMARCB1/INI1 occurring through a chromosomal translocation or deletion that results in loss of protein expression identifiable by immunohistochemistry. The management of RMC is radical nephrectomy with retroperitoneal lymph node dissection followed in most cases by systemic chemotherapy. At the time of diagnosis 70% of patients have local lymph node involvement with one site of metastatic disease and 30% have two sites of metastatic involvement, most commonly lymph node, lung, liver or the contralateral kidney. Cytotoxic chemotherapy with platinum-based regimens has demonstrated partial and complete responses with clinical benefit in several case series.  No evidence points to the benefit of screening patients with sickle cell trait for RMC because no feasible schedule and modality of screening would have an increase chance of identifying presentation of disease at an early stage. No effective measure exists for prevention of this type of renal malignancy. RMC carries a dismal prognosis with less than 5% surviving longer than 36 months.     

Epidermolysis Bullosa

Epidermolysis bullosa (EB) is a spectrum of rare, inherited, blistering bullous skin disorders primarily affecting the skin and pharyngoesophageal mucosa. EB affects approximately two to 4 per 100,000 children each year in the USA. EB is caused by a mutation in the genes that encode any of the structural components of keratinocytes and dermoepithelial junction. The mutation causes changes in proteins that are responsible for adhesions defects between cutaneous structures leading to blister formation. Autoantibodies to collagen VII binding to the anchoring fibril zone and inducing mucocutaneous blistering have been found in the acquired form of the disease in adults. EB is classified into four main groups according to location of skin separation. The four groups include EB simplex (intraepidermal layer), junctional (within the lamina lucida of the basement membrane), dystrophic (below the basement membrane) and a mixed type referred as Kindler syndrome (mixed skin cleavage pattern). EB can be localized or systemic. Cutaneous findings include blisters, scars, pigmentation changes, alopecia, absent or dystrophic nails and deformity of hands and feet. Extracutaneous symptoms of EB might affect eyes, teeth, oral mucosa, genitourinary, gastrointestinal, respiratory and musculoskeletal. The diagnosis of EB can be made from a skin biopsy, genetic mutational analysis or detecting autoantibodies bound to the basement membrane zone and in the serum against collagen VII. Gastrointestinal complications of EB include blistering and stenosis of the esophagus causing dysphagia and weight loss, gastroesophageal reflux disease, hiatal hernia, gastritis, protein losing enteropathy, anal fissure, megacolon, inflammatory bowel disease and constipation. Constipation is one of the most common clinical features of EB occurring in 40-75% of cases. Constipation occurs when defecation is painful due to perianal blisters and fissures leading to fecal retention. Blister formation in the oral mucosa can cause scarring resulting in microstomia and ankyloglossia which restrict food ingestion. Teeth might be structurally defective with poor quality enamel. Anemia is a frequent and serious complication of severe EB. The more severe the EB types, the more extensive the nutritional impairment. Feeding via gastrostomy should be initiated before the onset of malnutrition in order to improve growth recovery, and before the age of ten to allow pubertal development which has a positive psychological impact. Pharynx and esophageal strictures are a common and very morbid complication of EB resulting in dysphagia and odynophagia. Pneumatic dilatation using a high-pressure hydrostatic balloon catheter is the gold standard of treatment of symptomatic esophageal stenosis. Medical therapy of EB can include neutrophil targeting therapy, immunosuppressors, immunoglobulin, monoclonal antibodies, tumor necrosis factor inhibition, steroids and gene therapy.