PSU Volume 57 NO 01 JULY 2021

Neonatal Gastrostomy

One of the main reasons for prolonged hospitalization in newborn infants is delay in achieving full oral feedings. Infants who are unable to orally feed or have insufficient oral intakes require longer hospitalization after birth. Prematurity impacts negatively in the attainment of feeding milestones and 40% of infants referred to feeding clinics are born preterm. Infants may not be able to achieve full oral feedings due to congenital anomalies, being congenital heart disease one of the main reason, genetic conditions, neurologic injury, respiratory insufficiency and extreme prematurity. Feeding difficulty in infants in the neonatal period are related to sensory or motor neurologic vulnerabilities, static or progressive neurological disease, behavioral deficits, chronic lung disease, gastrointestinal disorders or a combination of all of these etiologies. When the neonate cannot consume adequate oral feeding, is gavage-tube feeding dependent, suffers from postprandial related cardio-respiratory spells, refuse to feed or has poor sucking ability a gastrostomy tube placement is performed. Gastrostomy placement is most strongly associated with bronchopulmonary dysplasia, intraventricular hemorrhage or periventricular leukomalacia and small for gestational age status. Gavages tubes when dislodge  results in a high choking and aspiration risk, are associated with leaks, infection,  reflux and feeding aversion. Nevertheless, home nasogastric feeding is a particular good alternative in infants discharge home on room air or nasal cannulas who are taking almost 50% of feeds orally.Gastrostomy tube are either placed open, laparoscopically or using endoscopic technique (PEG) depending on the preference of the surgeon. Gastrostomy tubes are placed when the baby attains at least 3 Kg of weight. Surgeons are moving to laparoscopic gastrostomy as the standard of care. Carbon dioxide insufflation and absorption during short laparoscopic procedures have demonstrated no significant alteration in cerebral or renal oxygenation or oxygen extraction. Premature infants that undergo gastrostomy placement have a significant increased risk of both inpatient readmission and emergency department visits within three months of NICU discharge. One-third of infants with g-tube have at least one emergency department visit and 9% multiple, with inadvertent removal/misplacement of the tube being the most common cause. For NICU infants who cannot feed or take medications by mouth, gastrostomy tube represents a safe way of administering nutrition and medications for long periods of time. After placement of the g-tube, infants may take more than two weeks to gain weight at rates seen prior to the surgery. Weight gain and appropriate growth occur more frequently in the population of children with neurodevelopmental disability when g-tubes placement occurs early, before morbidity and malnutrition become evident. Additional benefits of g-tube placement in newborns include safety of administration of nutrients, fluids, and medications, as well as facilitating discharge planning, including parental comfort and decreased stress regarding the long-term nutritional status of the baby.     

Multiple Endocrine Neoplasia Type 2

The multiple endocrine neoplasia type 2 (MEN-2) is a rare autosomal dominant inherited disorder caused by a germline mutation in the RET protooncogene with a prevalence of one in 30,000 live births. The RET protooncogene encodes the transmembrane tyrosine kinase receptor on chromosome 10q11.2. MEN-2 consists of three different syndromes: the MEN-2A (80-90%) characterized by medullary thyroid carcinoma (MTC), pheochromocytoma and primary hyperparathyroidism, the MEN-2B (5-10%) characterized by MTC, pheochromocytoma in children with distinct physical manifestation such as marfanoid habitus and multiple neuromas, and the familial MTC. Direct DNA analysis allows identification of children with MEN-2A. MTC is usually the first neoplasm to develop in 90-100% of cases, and the most common cause of death in MEN patients. This is the reason why prophylactic total thyroidectomy before the age of 5 years is recommended to those with the RET protooncogene mutation of codon 634 in the extracellular domain of the receptor. MTC in MEN-2 children can be cured by surgically removing all the c-cells at risk of becoming malignant. Calcitonin is utilized as marker of residual or recurrent disease. Pheochromocytomas has an incidence of 50% in MEN-2 syndromes, they are diagnosed at an earlier age, mostly of adrenal origin, rarely becomes metastatic, although they most almost always develop bilaterally. Management is surgical excision of the tumor harboring the pheochromocytoma. Cortical sparing adrenalectomy can be performed as part of bilateral adrenal resection. Hyperparathyroidism caused by hyperplasia of the gland occurs in 35% of patients with MEN-2. A group of children with MEN-2A develop Hirschsprung's disease (HD). Diagnosis is through rectal biopsy and management is pull-through surgery. In MEN-2B, pheochromocytomas develop in 50% of patients and all patients have neural gangliomas, particularly in the mucosa of the digestive tract, conjunctiva, lips and tongue. MEN-2B do not develop hyperparathyroidism. MTC in MEN-2B develop at a very young age (infancy) and appears to be the most aggressive form of hereditary MTC. Prophylactic total thyroidectomy is recommended before the age of two years in children with MEN-2B. Gastrointestinal ganglioneuromatosis is the predominant etiology of most alimentary tract symptoms in children with MEN-2B, resulting in thickening of myenteric plexus and ganglion cell hypertrophy leading to loss of normal bowel tone, distension, segmental dilatation and megacolon, though the number of ganglion cells is not reduced or absent as with HD. They develop constipation and intermittent diarrhea. Management is conservative, as symptoms are less severe than MEN-2A with HD. Marfanoid habitus is present in 65-75% of children with MEN-2B characterized by elongated face, large hands and feet with relatively long extremities. Skeletal anomalies include lordosis, kyphosis, joint laxity and talipes equino varus. 86% of MEN-2B are unable to shed tears. Familial MTC represent the remaining hereditary MTC cases and is characterized by presence of MTC without pheochromocytoma, hyperparathyroidism or physical characteristics of MEN-2B. MTC has a late onset with a good prognosis in the majority of familial cases. Late genetic testing, surgery beyond recommended age and elevated basal calcitonin levels are factors associated with higher rate of MTC in the specimen. No lymph node metastasis is present with basal calcitonin below 40 pg/ml. Above that level or in the presence of clinical palpable lymph nodes central lymph node dissection is recommended during thyroidectomy.      

Functioning Adrenocortical Tumors

Adrenocortical tumors (ACT) in children are rare, comprising 10-25% of all adrenal neoplasms. It is estimated that 25 new cases are seen each year in the US. The incidence is high in southern Brazil due to a high rate of mutation in the tumor suppression gene p53. Most of these tumors (95%) are functional producing hormones such as androgens, cortisol, aldosterone and estrogens in decreasing order of frequency. In cases who present with virilization, the most prominent symptom is rapid growth, acne, deepening of the voice, advanced bone age, clitoromegaly or penile enlargement. Functional adrenocortical tumors have a good prognosis when managed appropriately. Functioning ACT has a peak presentation during the first decade of life and occur more commonly in females. A family history is common in cases of ACT.  Survival rates are better in children with ACT than adults. ACT in children are associated with Beckwith-Weidman, MEN-1, Carney complex, congenital adrenal hyperplasia or Li-Fraumeni syndromes. The most common clinical presentation is virilization, followed by cushingoid features, hypertension, hyperestrogenism or a combination of these clinical manifestations. Adrenocortical adenomas and carcinomas can occur both in children with ACT. Presence of metastasis is absolute evidence of malignancy. Criteria suggesting malignancy include large tumor size, tumor weight exceeding 400 gm, extension into periadrenal soft tissue,  high nuclear grade, high mitotic rate per high power field (> 15 mitotic figure per 20 HPF), atypical mitosis, diffuse architecture, necrosis, capsular invasion and vascular invasion. ACT in young children and infants are more likely associated with the best overall prognosis and may not be as uniformly fatal as they are in older children. A thorough hormonal evaluation is needed for a precise classification of functioning ACT even if there is no clinical sign or symptom of hormone excess. Most ACT are located in the left adrenal gland. Most imaging modalities (US, CT and MRI) can detect the adrenal tumor. Management of ACT is surgical excision of the affected adrenal gland. The laparoscopic approach for removing the adrenal gland is the gold standard in all functioning ACT except the adrenocortical carcinoma, since minimal tumor spillage changes negatively the prognosis dramatically. In the postoperative follow-up, positron emission tomography with computer tomography (PET-CT) can be helpful in the detection of secondary lesions. Cryoablation should be considered in rare selected cases of tumors that are not amenable to surgical resection.  

PSU Volume 57 NO 02 AUGUST 2021

Mucous Fistula Refeeding

Neonates require enterostomy for a variety of conditions such as congenital atresias, meconium ileus, midgut volvulus, necrotizing enterocolitis, spontaneous bowel perforation and rarely gastroschisis. Substantial surgical resection is associated with a short residual length of bowel, often with a proximal stoma and distal mucous fistula. Stomas located in the jejunum or proximal ileum are classified as high output stomas resulting in production of large ostomy losses, fluid and electrolytes imbalances, metabolic acidosis, impaired absorption of fat, protein and other nutrients. In neonates with jejunal enterostomy and mucous fistula a significant length of bowel may be defunctionalized and not be able to be used for absorption of nutrients and electrolytes. Though they  anatomically have near normal length of bowel, the higher the enterostomy, the higher the complications associated with a functional small bowel syndrome. These infants rely on total parenteral nutrition (TPN) for growth and development. Mucous fistula refeeding (MFR) is the practice of collecting proximal ostomy effluent and reinfusing it into the distal mucous fistula. Refeeding the distal defunctionalized small bowel through the mucous fistula using the proximal succus entericus secretions can reduce the complications associated with a short bowel syndrome. The clinical benefits of MFR include simplified control of fluids and electrolytes balance in patients with high stoma output, optimal utilization of the remaining absorptive capacity for enteral nutrition, and reduction of gastrointestinal proximal stoma secretions up to 30%. MFR can be used with and without TPN preventing the atrophy of the distal bowel while preparing it for reanastomosis. Refeeding the proximal stoma effluent through the distal mucous fistula uses the absorptive surface of the distal bowel for nutrient absorption, stimulates mucosal growth and intestinal adaptation and prevents atrophy of the villi of the defunctionalizedl bowel. The increase absorptive function from the added length of intestine may reduce the requirement for parenteral nutrition, promote better weight gain and help eliminate cholestasis by stimulating the enterohepatic circulation.  The aim of the MFR technique in infants who have undergone bowel resection is to prime the bowel with luminal feeding promoting intestinal adaptation such as cell hyperplasia, bowel hypertrophy, lengthening and heightening of villi, improved peristalsis and mucosal growth. Strong intestinal growth stimulants including peptides and nutrient substances present in high concentration in the proximal enterostomy effluent induce substantial bowel lengthening and hypertrophy. Disuse atrophy of distal loop can be prevented. A further advantage of the MFR technique is simplification of the control of fluids and electrolytes balance in neonates with a high stoma that has a large output. Indications for refeeding of stoma effluent into the mucous fistula include the presence of a proximal stoma, a high-output enterostomy, electrolytes disturbance or failure to achieve adequate weight gain. Prior to initiation of MFR, patency of the distal bowel is ensured by means of a contrast fluoroscopy study through the mucous fistula. Infuse rate should not exceed 6-10 ml/hr with output refeeding performed every 3 hours to avoid bacterial overgrowth of the effluent to be used. Enteral refeeding technique is safe, reduce hospital stay, improves weight gain and potentially reduces TPN use and related complications in infants with small bowel syndrome and high output enterostomies. Complications associated with MFR include bowel perforation with the use of the catheter, bleeding, bacterial overgrowth if there is a delay between collection and refeeding of the stoma effluent.

Atypical Mycobacterias

Atypical mycobacteria infection refers to disease produce by Nontuberculous mycobacteria (NTM).  They are environmental acid-fast organisms isolated from soil, water, milk, eggs, vegetables and animals transmitted to humans through the respiratory system. More than 130 species have been identified, many of which cause human disease. In children, infection with NTM can result in cervical lymphadenitis, skin and osteoarticular infections, lung disease (predominantly in children with chronic lung disease), and disseminated disease infection in immune-compromised children. Mycobacterium Avium-Intracellulare complex (MAC) is usually the most frequently NTM isolated in children. Cystic fibrosis and Mendelian susceptibility to mycobacterial disease are two distinct inborn genetic disorders associated with NTM disease. Of the acquired disorders associated with NTM, HIV infection predominates. The most common NTM-associated disease in healthy children is chronic cervicofacial lymphadenitis most frequently caused by mycobacterium avium/Intracellulare complex. The oropharyngeal mucosa is the typical portal of entry as toddlers place contaminated objects in their mouths. NTM lymphadenitis occur early in childhood with 80% in children younger than five years, with a mean age of diagnosis of 2.5 years. Children present with history of unilateral lymph node swelling usually affecting the jugulodigastric, parotid or preauricular, submandibular and posterior triangle lymph node persisting for weeks to months despite antibiotic therapy. The infection is not associated with systemic symptoms or signs. Involvement of submandibular lymph nodes represents the most frequent localization (80%). The affected lymph node can go from a painless firm mass with increased vascularity, to a more fluctuant mass due to liquefaction. Next the skin over the lymph node takes a violaceous discoloration which might lead to fistulization that may discharge for months. Spontaneous healing usually occurs within six months. Pulmonary NTM disease is indistinguishable from pulmonary tuberculosis and is usually associated with cystic fibrosis. Diagnosis of NTM disease requires clinical, radiological and microbiological assessment. A tuberculin (PPD) induration greater than 5 mm at 48 hours suggest a diagnosis of NTM infection. Microbiological diagnosis of NTM disease is achieved by detection of the causative organisms by PCR (more sensitive; more rapid), or bacterial culture (slow growth). Molecular detection of NTM in lymph node biopsy samples is more sensitive than bacterial culture. Histopathology reveals necrotizing granulomatous inflammation associated with caseous necrotic areas. Interferon gamma release assay (IGRA) is positive in 70-80% of tuberculosis lymphangitis cases and generally negative in NTM. The characteristic radiological feature of NTM infection is the presence of central cavitating lesions represented by low-density necrotic material. Management of NTM disease relies on combination of several antibiotics, with macrolide being the cornerstone of treatment. Treatment of NTM adenitis depends on disease stage and severity. Lack of response to three months of antibiotic therapy is considered a treatment failure. Surgery remains an option for lesions that show evidence of progression to cutaneous involvement.  Complete surgical excision of the affected lymph node, as soon as possible, is regarded as the best curative option. Secondary wound infection and permanent injury to the facial nerve is a major concern with surgical excision of affected lymph nodes. In cases of incomplete excision of the infected lymph node a macrolide-containing drug regimen should be given. Fluctuant lesions are managed more frequently with antibiotics, while a firm lesion can be observed for spontaneous resolution.     

Accessory Cardiac Bronchus

Accessory cardiac bronchus (ACB) is a very rare, poorly recognized, usually asymptomatic congenital anomaly of the tracheo-bronchial tree. ACB is a supernumerary bronchus usually arising from the inner wall of the right main or intermediate bronchus, opposite to the origin of the right upper lobe bronchus. Most cases are incidental findings in asymptomatic adult patients. ACB is a true bronchus, with normal epithelial lining and cartilage walls. The ACB is thought to be a remnant of the cardiac bronchial bud that failed to regress during embryogenesis. Three anatomic variations of ACB have been described: a short, blind ending type, an accessory lobed type which branches into rudimentary ventilated lobules, and a long diverticular type lacking any further arborization. The configuration may range from a short diverticulum where no lung tissue is observed and it appears as a stump, to a longer structure where surrounding lung tissue is present. 70% of ACB are of the diverticulum type ending blindly. Usually, ACB arises from the medial wall of the bronchus intermedius (75%), has a mean diameter of 8.7 mm and a mean length of 12 mm. It is lined by a normal bronchial mucosa, has cartilage within its wall and is usually demarcated by a spur at its origin from the normal bronchus. Though most cases are asymptomatic, ACB may be a site of chronic inflammation and produce several complications including recurrent secondary lung infection, hemoptysis, chronic cough and rarely malignant transformation. Diagnosis is established with chest CT-Scan. Bronchoscopy might miss the accessory bronchus due to constriction by repeated inflammation. The recognition of an ACB is important since it should be differentiated from acquired bronchial fistula, diverticulum or adenoid recess. Surgical excision of ACB is recommended when symptomatic, or in asymptomatic patients with the lobed or long diverticular type because of the high probability of long-term complications. This can be accomplished using either minimal invasive thoracoscopy or open thoracotomy.

PSU Volume 57 NO 03 SEPTEMBER 2021

Androgen Insensitivity Syndrome

Complete virilization of a 46XY fetus depends on either androgens or a functioning androgen receptor. Androgen insensitivity syndrome (AIS) is an X-linked recessive genetic condition caused by an androgen receptor gene mutation situated in the Xq11-q12 region, which results in resistance to androgens in 46XY individuals. The disorder is characterized by the presence of a male karyotype with a female phenotype. AIS is divided into subtypes that include complete AIS (complete feminization of external genitalia), partial AIS (mainly female, mainly male or ambiguous external genitalia) and mild AIS (male external genitalia and impaired pubertal virilization). AIS is the most common disorder of sexual differentiation in individuals with 46XY karyotype. Mutations in the androgen receptor gene are found in more than 95% of individuals with complete AIS, while this occurs in 40% of partial IAS cases. Children born with complete AIS have female external genitalia, while those with partial IAS have atypical external genitalia. The characteristic features of this disorder include a female phenotype with normal breast development but absent or scanty growth of pubic and axillary hair. The disorder also includes a vagina of varying lengths along with the absence of the uterus, fallopian tubes and ovaries. Testicular secretion of Müllerian inhibiting substance suppresses development of the uterus, oviducts and upper one-third of the vagina in utero. Gonads in the form of testes are located at the internal inguinal ring, resides intraabdominal or can be palpable in the labia majora in children with complete AIS. Complete AIS is associated with amenorrhea and inguinal hernias in girls. The diagnosis is established with karyotype analysis, imaging studies (US, MRI) and a combination of hormonal dosages either at basal or after gonadal stimulation. There is an increased risk of gonadal tumors in patients with complete AIS. The invasive type II germ tumors encountered are the seminoma if the gonad is testis, and dysgerminoma if the gonad is considered an ovary. Seminoma is the most frequent testicular tumor in complete AIS with an age at presentation of more than 30 years. Currently, there are no clinically useful biomarkers available to guide clinicians in predicting tumorous risk other than direct gonadal histology and immunohistochemistry. If the gonads are removed due to the risk of future malignancy, hormone replacement therapy should be initiated and continued until the age of menopause. There is discrepancy regarding the timing of gonadectomy in patients with complete AIS. The consensus is to recommend delaying gonadectomy until postpubertal status is reached to allow for spontaneous puberty to develop through aromatization of testosterone into estrogen, since there is a very low risk of malignancy before puberty. Gonadectomy would necessitate initiation of hormone replacement therapy since androgens are necessary for skeletal development. Therefore AIS patients would require estrogen replacement to achieve and/or maintain normal bone mass. Delaying gonadectomy until patients are of an age to make their own medical decision remains safe, especially since the risk of malignancy before puberty is very low. Ultrasound surveillance should be utilized to screen patients for malignancy, should they decide to retain their gonads into adulthood.   

Anorchia

Congenital anorchia, also known as testicular regression or vanishing syndrome, is defined as the absence of one or both testes in a 46,XY individual with a male phenotype. Anorchia occurs unilateral in 97% of cases accounting for 10% of cases in which the testis is absent from the scrotum or inguinal canal. Testes are impalpable in 20% of cryptorchidism cases, with unilateral anorchia as the cause in 35-60% of them. Unilateral anorchia occurs in one of 5000 males. Bilateral or true congenital anorchia is rare, occurs in one of each 180 cases of cryptorchidism, or one in 20,000 male births. A few children with anorchia present with ambiguous genitalia or microphallus. Anorchia is a component of several malformation syndromes such as Cross syndrome, OEIS syndrome, Saldino syndrome and sirenomelia. Phenotyping into male external genitalia depends on anti-müllerian hormone (AMH) produce by Sertoli cells and testosterone produced by Leydig cells. This means that testes were present but disappeared in utero. The genetic cause of anorchia is not known. Laparoscopy has suggested that some cases of anorchia are the result of prenatal testicular vascular accidents associated with torsion during in-utero testicular descent. Infants with bilateral anorchia present with micropenis in almost 50% of cases. Upon examination palpable testes are absent, while during laparoscopy blind-ending spermatic cord and epididymides are usually present. In children with bilateral anorchia serum testosterone concentration is very low and does not increase in response to HCG stimulation. Serum AMH concentrations are usually undetectable in patients with bilateral congenital anorchia. Inhibin B is undetectable in most boys with bilateral congenital anorchia. Undetectable levels of AMH and inhibin B, along with elevated FSH and LH levels in a 46,XY karyotype is sufficient evidence for diagnosis of congenital bilateral anorchia. True bilateral anorchia must be differentiated from intra-abdominal bilateral cryptorchidism. Diagnosis is based on a combination of biochemical tests, karyotype, imaging studies and surgical/laparoscopic exploration. Surgical/laparoscopic exploration and histologic findings typically show nubbins of fibrous tissue devoid of any testicular tissue attached to a blind-ending vas deferens. Histopathology examination has confirmed the presence of germ cells in 0-16% of excised testicular remnants. Germ cell tumors cannot develop from a testis remnant that has no germ cell survival from the early embryonic primordial germ cells. Hence tumor development is extremely rare in remnants with germ cells. Nubbin excision should be performed if the internal ring is open with normal vessels. Management of congenital bilateral anorchia consists of testosterone replacement to stimulate penile length and induce sexual development. Testicular prostheses can be implanted in the scrotum for psychological and cosmetic reasons. Unilateral anorchia does not require hormonal management.

Mixed Gonadal Dysgenesis

Mixed gonadal dysgenesis (MGD) is a very rare disorder of sexual development characterized by gonadal asymmetry with an abnormal dysgenetic testis on one side and a streak gonad on the contralateral side. Phenotypic features of MGD is variable, and include normal males, females with or without turner-like physical characteristic, and cases of ambiguous genitalia. Most common MGD karyotype includes a 45,XO/46,XY mosaicism. Rare mosaic karyotype identified in MGD can include 45,XO/47,XYY or 45XO/46XY/47XYY. The phenotypic abnormalities are the result of incomplete inhibition of müllerian structures, and incomplete masculinization of external genitalia. 95% of MGD children have müllerian remnants and 75% of streaks gonads have an ipsilateral fallopian tube. 90-95% of patients with a prenatal diagnosis of 45,XO/46XY will be phenotypically normal male.  Clinically they present as children with ambiguous or abnormal genitalia, or adults with gonadal failure or short stature. Other associated problems in MGD include cardio renal malformations, gonadal blastomas and germ cell tumors. Patients with bilateral streaks are associated with the phenotype of a sexually infantile female, those with a streak and intra-abdominal testis present with clitoromegaly in a female, and those with one scrotal testis and an intraabdominal streak are associated with frank sexual ambiguity, and bilateral scrotal testis present as a male with short stature and gonadal failure. All of these cases with MGD are infertile. Diagnosis should be suspected with delay in puberty changes, short stature, webbed neck, and coarctation of the aorta. Diagnosis is established with karyotype, cytogenetic studies (FISH or PCR analysis), imaging studies (US, MRI) and laparoscopy. During laparoscopy a biopsy of each gonad should be ascertained before embarking in bilateral gonadectomy. In MGD, the gonadal phenotype ranges from streak gonads through dysgenetic to functioning testes.  Congenital adrenal hyperplasia should be rule-out clinically and biochemically. In patients with MGD the sex of rearing decision is usually female. The term Y-chromosome gonadal dysgenesis is used for both 46,XY and 45,XO/46,XY karyotype with MGD. Early correct diagnosis of Y-chromosome gonadal dysgenesis has a higher potential malignant risk. The risk of developing malignancy depends on how much Y material is present. The specific location on the Y chromosome that has been identified is the gonadoblastoma location known as the GBY region. Gonadal tumor development is one of the most important challenges in patients with MGD. The most common tumor observed is gonadoblastoma, followed by invasive germ cell tumor.  Gonadectomy for the Y-chromosome gonadal dysgenesis should be accomplished during the first decade of life since most tumors develop during the second decade. Neoplastic transformation of a germ cell in dysgenetic gonads, either gonadoblastoma or invasive germ cell tumor, occurs in 20-30% of 46,XY MGD patients.The child to be raised as a female will need clitoral recession and vaginoplasty in early infancy. If it is to be raised as male, then various types of hypospadias repair can be done, gonads can be replaced with prostheses, the prepenile scrotum reconstructed and Müllerian structures removed. 

PSU Volume 57 NO 04 OCTOBER 2021

Parastomal Hernia

Parastomal hernia (PH) is an incisional hernia that occurs within the surrounding of a stoma where abdominal content, typically bowel or omentum, protrude between the skin and bowel stomal edge surrounded by a hernial sac. Parastomal hernia is a common complication of various type of stomas. It can progress asymptomatic, resulting in an abdominal deformity, but it can lead to bowel incarceration and strangulation needing urgent surgery. In infants and young children the most common indications for performing a stoma include necrotizing enterocolitis, Hirschsprung's disease and anorectal malformations. In adolescent children the indication is intractable functional constipation, intestinal pseudo obstruction and inflammatory bowel disease. An ostomy prolapse in children is more common than parastomal hernia in children. Prolapse is more common after loop than end enterostomies. Patients with gastrointestinal motility disorders have a higher complication rate and more severe complications in comparison to the children without gastrointestinal motility disorders. In adults the two most common conditions associated with stoma construction include colorectal cancer and inflammatory bowel disease. It is believed that 30 to 50% of stoma will develop a parastomal hernia, and one-third of these cases will need surgical correction. End (colon) ostomies have a higher probability of developing a parastomal hernia than loop (ileum) ostomies. Risk factors associated with developing a parastomal hernia include age above 60 years, obesity, diabetes, tobacco consumption, systemic and local infection, COPD, steroid therapy, inflammatory bowel disease and cancer. The incidence of parastomal hernia as a recurrence after corrective surgery is lower when using mesh for the repair. Diagnosis of a parastomal hernia is by physical examination. In the vast majority of cases the only clinical symptom is a deformity of the abdominal wall around the stoma. Parastomal hernia can be overlooked in obese patients. The use of ultrasound, CT-Scan or MRI increases the diagnostic accuracy. Indications for surgical management of parastomal hernia are limited to those with severe symptoms and complications of bowel obstruction occurring in 30% of all hernia patients. Indications for surgical management include incarceration, strangulation, obstruction, parastomal fistula, perforation, ischemia, recurrent symptoms of obstruction, difficulty maintaining collection device, hernia-related pain, and problems with irrigation of the stoma. Several methods utilized for corrective surgery of a parastomal hernia include open transposition of the stoma, use of mesh reinforcement, or repair using minimally invasive technique. Transposition is associated with a lower risk of hernia recurrence when compared with local reconstruction. When mesh is utilized, it can be placed superficially (onlay technique), pre-peritoneally (sublay technique) or intraperitoneally (inlay technique). Laparoscopic technique relies on intraperitoneally implanted prosthetics. Reinforcement of the abdominal wall with prosthetic material is the method of choice since it promises good results and low incidence of complications and recurrences over long periods of time.  

Juvenile Granulosa Ovarian Tumor

Granulosa cell tumors of the ovary are rare benign ovarian sex cord-stromal tumors. Granulosa cell tumors are divided into a juvenile granulosa cell and adult granulosa cell variety tumor. Ovarian tumors account for approximately 1% of all tumors in children and adolescent. Juvenile granulosa cell tumor (JGCT) accounts for 67% of sex cord-stromal tumor in the pediatric population and  approximately 5-12% of all ovarian neoplasms in children. Nearly half of the patients are diagnosed in the first decade of life with a median age of presentation of 7 years. The clinical significance of JGCT is due to its estrogen secreting properties resulting in pseudo precocious puberty without ovulation. More than 80% of patients present with symptoms of precocious puberty including increased pubic hair, vaginal bleeding, breast enlargement and advanced bone age. In older ages and adolescents JGCT causes other manifestations such as hirsutism, abnormal uterine bleeding and abdominal discomfort. There is a high level of sex hormones and suppressed gonadotropin level in this condition. JGCT secretes estradiol due to the presence of theca cells that secrete androstenedione which is subsequently converted to estradiol by the granulosa cells. Inhibin A & B which are synthesized by the granulosa cells are also elevated supporting the diagnosis. A pelvic mass is usually present. The triad of a palpable adnexal mass, elevated serum estradiol and absent or decreased gonadotropin is almost diagnostic of JGCT. JGCT are usually large (averaging 12 cm) and in most cases limited to the ovary.  Under ultrasound granulosa tumors are solid and cystic or mainly solid with a spongiform appearance with the solid portion being heterogeneous in echogenicity. On MRI the solid component is typically isodense and enhances. Fluid-wave levels within the cystic component represent areas of hemorrhage. Granulosa cell tumors of the ovary rare calcify or spread to the peritoneum, unlike epithelial neoplasm. JGCT are typically unilateral and confined to the affected ovary at diagnosis. Hence, most cases (>90%) are diagnosed with FIGO Stage 1 which respond well to unilateral salpingo-oophorectomy. Surgery should be performed in this age group with unilateral oophorectomy only for stage 1. There is no role for simple ovarian cystectomy. Staging should include peritoneal cytology, exploratory laparotomy and unilateral salpingo-oophorectomy. Bilateral ovarian involvement is uncommon in stage 1 tumors and wedge biopsy is not recommended. Prognostic factors include the size of the tumor, degree of nuclear atypia and mitotic activity. Tumor rupture is not a negative prognostic factor. Serum estradiol, CA-125 and inhibin B may be used for follow-up postoperatively. Precocious puberty changes subside and physiologic puberty occurs at the normal expected age in all cases after tumor removal. Advance disease might need cytoreductive surgery followed by combination aggressive chemotherapy. Lymph node involvement is a rare phenomenon in sex-cord stromal tumors.    

Duct of Luschka

Ducts of Luschka are subvesical accessory biliary ducts located in the gallbladder fossa. They branch from the right hepatic or common hepatic duct, are not accompanied by artery or vein as other bile ducts draining liver segments (a portal triad is absent). Ducts of Luschka are small, less than 1-2 mm in diameter, usually originating from the lower aspect of the right hepatic lobe running along the gallbladder fossa and liver parenchyma. They do not open into the gallbladder. Drainage may be into intrahepatic or extrahepatic biliary ducts. Ducts of Luschka should be differentiated from hepatocystic ducts which are aberrant ducts that could drain a significant amount of liver parenchyma into the gallbladder or cystic duct. The reported prevalence of duct of Luschka is 4%. Injury to the ducts of Luschka during laparoscopic or open cholecystectomy can cause postoperative bile leak and peritonitis. Most injuries to the duct of Luschka occur after ligation and division of the cystic artery and cystic duct while dissecting the gallbladder from the liver fossa. These ducts can also be injured during liver resection, liver transplantation  and interventional radiological procedures. In very rare occasions the ducts of Luschka can be identified intraoperatively. Patients with bile leaks have variable clinical course presenting with mild abdominal pain, tenderness, fever or biliary peritonitis with sepsis. There is mild elevation of serum bilirubin and alkaline phosphatase. Timing of presentation of such leaks is usually within the first postoperative week. The patient with duct of Luschka leaks will develop a fluid collection (biloma) diagnosed by US or CT-Scan. A percutaneous drainage is usually necessary to drain the bile leak. Performing a fistulogram through the draining catheter will demonstrate a communication with the biliary tree. Though a HIDA scan will demonstrate a bile leak, it cannot give an anatomical impression of where the bile leak is coming. MRCP can diagnose a leaking duct of Luschka. ERCP is the standard mode of diagnosing a duct of Luschka leak. ERCP can also be therapeutic by reducing intrabiliary pressure with sphincterotomy and endobiliary stent placement. The management of a duct of Luschka leak depends on the clinical condition of the patient. Asymptomatic patients with a low output leak can be managed with simple drainage. Spontaneous resolution of the leak may occur because accessory ducts do not drain a significant portion of the liver. Should the leak produce a higher output of bile, ERCP with sphincterotomy, stenting or nasobiliary tube placement should be in order. Patients with severe symptoms and those where the leak persists despite endoscopic treatment should be reexplored and ligation of the leaking duct performed.    

PSU Volume 57 NO 05 NOVEMBER 2021

Anorectal Myectomy

In 1964 Lynn device a surgical procedure for short segment Hirschsprung's disease (HD). This procedure was later utilized for chronic idiopathic constipation not associated with Hirschsprung's disease and for children who suffered from anal sphincteric achalasia after a pull-through procedure. A rectal biopsy is warranted in cases of chronic constipation to determine the presence or absence of ganglion cells. The biopsy can be performed using a suction biopsy tool in children less than three months of age, while a full-thickness biopsy might be needed for children above six months of age. Thus will determine if the child has aganglionosis or not. The anorectal myectomy consists of an outpatient procedure. Dissection of the internal sphincter from the mucosa and external sphincter is performed in the intersphincteric plane. The dissection is extended proximally for five to 7 centimeters. Excision of one centimeter wide strip of the internal sphincter muscle is performed for the length of the dissection. Barium enema suggests the presence of ultra-short segment HD but may not indicate precisely the extent of the disease and in some children a constricting segment may not be demonstrable. Confirmation will only take place after a rectal biopsy is performed. If after anorectal posterior  myectomy for HD there is no relief of symptoms then the child will need a major procedure for cure. Anal stricture and incontinence have been reported as complications of myectomy. The advantage of this operation is it's relatively simplicity and in addition serves as both diagnostic and therapeutic. Internal anal sphincter achalasia is a clinical condition with a presentation similar to HD. The diagnostic criteria for anorectal sphincter achalasia are based on anorectal manometry showing absence of the recto-inhibitory reflex associated with a normal rectal biopsy. Anorectal sphincter achalasia reflects the failure of relaxation of the internal sphincter. The exact pathogenesis and pathophysiology of internal sphincter achalasia is not fully understood. Patients present with constipation and soiling with or without abdominal distension. Nutritional support, laxatives and enemas are the first line of treatment of chronic constipation associated with achalasia of the sphincter  and approximately 85% of cases could improve or cure by conservative medical management. Due to an inadequate response to medical treatment of constipation other children are selected for surgery.  Anorectal myectomy relieves more than 60% of patients with chronic refractory constipation associated with internal sphincter achalasia. In children with internal anal sphincter achalasia, posterior anorectal myectomy of the internal sphincter is a more effective treatment option when compared with intrasphincteric Botox injection. Anorectal myectomy is an effective and safe procedure in patients suffering from persistent chronic constipation in spite of medical treatment. Is also the definitive treatment for children and adults with ultrashort-segment Hirschsprung's disease.

Vaping Lung Injury

Electronic cigarettes are alternative tobacco products that deliver nicotine without the tobacco smoke. They are devices that produce an aerosol by heating a liquid that contains a solvent (vegetable glycerin, propylene glycol) on one of several flavoring with or without nicotine. Each device  structurally comprises four components: a battery, a reservoir for the liquid, a vaporizing chamber with a heating element and a mouthpiece for inhalation. Evaporation of the liquid during heating followed by rapid cooling forms the aerosol which after inhaled is term "vaped". This method of smoking is less harmful as compared with cigarette use since it's not associated with inhalation of combustible products of tobacco which is more carcinogenic. While most e-cigarettes deliver nicotine and a flavoring agent, many contain cannabis-based compounds used as a substitute for traditional marijuana. Vaping use has increased significantly between high school and middle school students. Vaping has been associated with increase odds of myocardial infarction, thermal injury due to explosions, seizures and psychosocial effects due to addiction. Lately electronic cigarettes have been associated with significant lung injury (EVALI = electronic vaping associated lung injury), with the majority of cases in teenage and young adult males. Vaping generates harmful carbonyl compounds such as formaldehyde, acrolein and acetaldehyde implicated in the development of oxidative stress and release of inflammatory mediators causing airway epithelial injury. Most associated vaping lung injury involves THC, the active ingredient in marijuana and vitamin E acetate which is used a diluent. Vitamin E acetate when heated and aerosolized produce ketene, an extreme irritant of airways further propagating inflammation. Common respiratory symptoms found in this patients include shortness of breath, cough, pleuritic chest pain and hemoptysis. Gastrointestinal symptoms of nausea and abdominal pain, associated with fever and chills are reported in the majority of cases. This inflammation can progress to hypoxemic respiratory failure decreasing oxygen saturation. Mechanical ventilation will be required in 15-30% of these patients. Chest films and CT-Scans show bilateral hazy or consolidate opacity with lower lobe or centrilobular ground glass nodule appearance. Pleural effusions are rarely seen. Vaping associated lung injury(EVALI)  is a diagnosis of exclusion with the case definition being a history of vaping within 90 days of symptom onset, abnormal imaging and absence of an alternative diagnosis such as infection. An infectious workup should be performed in all cases. Bronchoscopy with bronchoalveolar lavage with transbronchial biopsy should be performed to exclude other causes of injury. Pathology of specimen shows organizing pneumonia, diffuse alveolar damage, lipoid pneumonia, acute fibrinous pneumonitis or a combination of these patterns. Cytology of alveolar lavage revels foamy macrophages and pneumocyte vacuolization. Labs evaluation reveals leukocytosis, elevated inflammatory markers and elevated lactate dehydrogenase levels. Management consists of antibiotics, steroids, high-flow oxygen therapy, mechanical ventilation and extracorporeal membrane oxygenation. Prognosis is excellent in young patients with most improving after a week of therapy. Due to the alarming number of EVALI cases a public crisis has been declared.     

Clavien-Dindo Classification

The Clavien-Dindo classification (CDC) is a standardized system for the registration of surgical complications. It was initially based in three definitions of different outcomes after surgery: failure to cure, sequelae and complications, completed by a system ranking complications according to severity. Clavien focussed on grading the severity of complications on the basis of the therapeutic consequence required to manage the complication. The classification can be seen in the Table below. There are five grades of evaluation of a surgical complication. Grade 1 includes any deviation from the normal postoperative course without the need for pharmacological treatment or surgical, endoscopic or radiological intervention. Acceptable therapeutic regimens include drugs as antiemetics, antipyretics, analgesics, diuretics and electrolytes. This grade includes wound infections opened bedside. Grade II includes requiring pharmacologic treatment with drugs other than those allowed for Grade 1 complications. Grade II complications are those that result in deviations from the normal postoperative course including unplanned or additional clinic or office visits that can be managed as outpatients without additional invasive, radiographic or surgical procedures. This includes wound infections, transient nerve injury, deep-vein thrombosis necessitating anticoagulation. Grade III requires surgical, endoscopic or radiological intervention. Grade III is subdivided further into III-A if intervention does not require general anesthesia, and Grade III-B if the intervention requires general anesthesia. Grade IV is a life threatening complication, including CNS complication or requiring intensive care management. Grade IV is subdivided into Grade IV-A if it involves single organ dysfunction (including dialysis) and Grade IV-B if it includes multiorgan dysfunction. Grade V is death of a patient. A suffix "d" is added to each grade if the patient suffers a complication at the time of discharge. The label indicates the need for follow-up to fully evaluate the complication. Clavien-Dindo Grade II is the most represented complication overall accounting for almost 20% of all patients. The CDC can be applied to patients who have undergone elective and emergency surgery during the first 30 postoperative days. Complication rates during emergency cases are higher than in elective procedures. Complications are higher in neonates than in other pediatric group. The advantage of this system is that all possible adverse events are included. The Clavien-Dindo grading system while widely used in general, transplantation and orthopedic surgery, it has been sporadically used in pediatric surgery to identify complications related to jejunal feeding, after repair of congenital duodenal obstruction, after Nuss procedure, after ileostomy and colostomy procedures, and after transanal endorectal pull-through for Hirschsprung's disease. The most recurring complication in pediatrics using the CDC is wound infection and post-appendectomy fluid collection/abscess. A high complication rate after enterostomy formation in children with motility disorders was identified using the CDC. Virtually all current general surgical publications with morbidity as an outcome measure use the Clavien-Dindo classification.        

References:
1- Clavien PA, Barjun J, de Oliveira ML, et al: The Clavien-Dindo Classification of Surgical Complications. Five-Year Experience. Ann Surg. 250: 187-196, 2009
2- Dodwell ER, Pathy R, Widmann RF, et al: Reliability of the Modified Clavien-Dindo-Sink Complication Classification System in Pediatric Orthopaedic Surgery. JB JS Open Access. 3(4):e0020, 2018
3- Hoff N, Wester T, Granstrom AL: Classification of short-term complications after transanal endorectal pullthrough for Hirschsprung's disease using the Clavien-Dindo-grading system. Pediatr Surg Int. 35(11):1239-1243, 2019
4- Thompson H, Jones C, Pardy C, Kufeji D, Nichols E, Murphy F, Davenport M: Application of the Clavien-Dindo classification to a pediatric surgical network. J Pediatr Surg. 55(2):312-315, 2020
5- Pio L, Rosati U, Avanzini S, et al: Complications of Minimally Invasive Surgery in Children: A Prospective Morbidity and Mortality Analysis Using the Clavien-Dindo Classification. Surg Laparosc Endosc Percutan Tech. 27(3):170-174, 2017
6- Vriesman MH, Noor N, Koppen IJ, Di Lorenzo C, de Jong JR, Benninga MA: Outcomes after enterostomies in children with and without motility disorders: A description and comparison of postoperative complications. J Pediatr Surg. 55(11):2413-2418, 2020

PSU Volume 57 NO 06 DECEMBER 2021

Acute Traumatic Coagulopathy

Trauma causes over 4 million deaths per year in the USA. Most potentially preventable deaths are due to bleeding. Disruption of the hemostatic equilibrium occurs at the moment of traumatic impact in children and adults. Tissue injury and blood loss during trauma causes an endogenous acute coagulopathy referred to as acute traumatic coagulopathy (ATC). Traumatic injury generates dysfunction of the coagulation, anticoagulation and fibrinolysis system, featuring a hypocoagulant state with prolongation of the prothrombin time (PT) and/or activated partial thromboplastin time (aPTT). The PT and INR have been suggested as the more sensitive test to the multiple coagulation factor deficiencies associated to ATC. ATC develops rapidly and has been identified within minutes of injury. Severe tissue trauma and systemic hypoperfusion are prerequisites for development of ATC. The worst coagulopathy is seen in patients with injury severity scores above 35 and base deficits less than 12 mEq/L. Others mediators such as hypothermia, acidosis, and hemodilution develop later after injury due to hemorrhage, hypoperfusion and exposure and resuscitation with hypocoagulable products. Presence of ATC during hospital admission is independently associated with fourfold higher mortality and significantly greater transfusion requirements. The overall length of mechanical ventilation, ICU and hospital stay is longer in injured patients with acute traumatic coagulopathy versus those with normal hemostasis on admission. Patients presenting with ATC have a mortality approaching 50%. An INR greater than 1.3 on admission is the most predictive of risk of death over other characteristics labs. The higher the INR the higher the risk of mortality. Endogenous systemic anticoagulation and fibrinolysis have emerged as probable mediator of ATC. Coagulation is acutely impaired after injury, starting with fibrinogen concentration declining rapidly. Systemic anticoagulation via activation of protein C is the most important functional mediator of ATC. Fibrinolysis is also a functional component of ATC. Injury and hemorrhagic shock cause primary platelet impairment. The vascular endothelium is an active participant in the pathophysiology of ATC as it capture thrombin and accelerates protein C activation 1000-fold. ATC is not a consumptive coagulopathy, since it's characterized by dysfibrinogenemia, systemic anticoagulation, impaired platelets function and hyperfibrinolysis. The most consumed coagulation factors following injury are fibrinogen and factor V. Reproducing whole blood by transfusing injured patients with a balanced ratio of packed blood red cells, fresh frozen plasma and platelets while minimizing crystalloid resuscitation is associated with a reduced mortality. High doses of fresh frozen plasma (10-20 ml/kg) are recommended to control the severe traumatic bleeding as soon as possible. FFP and PRBC at a predetermined ratio of 1:2 is recommended.  Platelet transfusions are recommended to maintain a goal above 50K/L in polytrauma, and > 100K/L in central nervous system injury. Correction of hyperfibrinolysis using tranexamic acid is the final component to effective damage control resuscitation.      

PICC Lines

Vascular access is a very important aspect of care for children and adults. Peripheral inserted central venous catheters (PICC) lines are required by almost one-third of neonates and children admitted to intensive care units. Indications for PICC lines include intravenous access, long-term antibiotics therapy, infusion of blood products and total parenteral nutrition. Using ultrasound guidance, PICC lines are easy and safe to insert due to placement in a peripheral vein in the upper limb (cephalic or basilic vein) with the tip at a central location in the superior or inferior  vena cava  allowing high osmolality solutions to be delivered. Risk of hemothorax and pneumothorax associated to central line placement is also avoided. The use of the axillary vein for PICC line insertion in premature neonates can significantly reduce the frequency of complications. Infants with abdominal surgical pathology who have PICC lines placed in the lower limb are at greater risk for major complications related to venous thromboembolism. PICC lines are inserted ultrasound-guided either using the modified Seldinger technique or the direct sheathed-needle puncture technique. Both have similar complication rates. The tip of the PICC lines is confirmed with a standard chest film. The most common complications of PICC lines include in order of frequency local inflammation at the site of insertion (redness and swelling), infection with sepsis, thromboembolism and mechanical. An infection occurs when there is a positive peripheral or central blood culture or a positive catheter tip culture after removal in the presence of clinical signs of catheter-related sepsis. The surgical neonate has a PICC infection rate of 10-25% comparable to the infection rate of Broviac catheters. Coagulase-negative staphylococcus is the most common organism isolated from positive cultures in PICC lines. Attempted catheter sterilization with antibiotics can lead to complicated bacteremia. Complicated bacteremia is defined as the presence of end-organ damage, multiple positive blood cultures or death. End-organ damage is defined as presence of osteomyelitis, vital organ abscess, positive echocardiogram with vegetation, or a positive lumbar puncture. Lack of improvement of inflammatory markers or two positive blood cultures in spite antibiotics therapy for sepsis needs line removal. Recommendations to reduce the incidence of catheter associated bloodstream infection (CABSI) include cleaning hands before placement, wearing full barrier precautions during insertion, using chlorhexidine to clean the skin, using prepackaged insertion bundles and assessing the daily need for the line. There is also a decrease in CABSI when lines are placed in the operating room. Withdrawing blood from catheters less than 3 Fr.increase the occlusion rate of PICC lines. The use of central lines is the most common cause for thrombosis in neonates and infants preterm babies. Catheter-related venous thromboembolism can be asymptomatic or can result in complications such as deep vein thrombosis, portal vein thrombosis, Budd-Chiari, superior vena cava syndrome, intracardiac thrombosis or pulmonary embolism.

Congenital Thrombophilia

Thrombophilia is defined as an increased risk of developing hypercoagulability and venous thrombosis. Thrombophilia may be congenital or acquired. Although thrombosis may occur in either or both venous and arterial vessels, the term thrombophilia is usually utilized for venous thromboembolism (VTE). Main causes of congenital thrombophilia are classified as loss of function such as deficiency of antithrombin, protein C and protein S, or a gain of function such as activated protein C resistance due to factor V Leiden mutation, hyperprothrombinemia due to presence of the prothrombin mutation, or dysfibrinogenemia due to impairment of the relevant metabolic pathway. Acquired risk factors for developing thrombophilia include antiphospholipid antibodies, detected as lupus anticoagulants and/or anticardiolipin antibodies and/or anti-B-2-glycoprotein-I antibodies. Laboratory testing for thrombophilia should be undertaken in any young patients who experience an unprovoked thrombotic event and those with recurrences. The identification of risk factors may permit genetic counseling, modification of the patient lifestyle to avoid future risk and the ability to identify relatives at risk. Thrombophilia testing does not substantially help to predict or reduce the incidence of thrombosis recurrence. The intensity and duration of anticoagulation treatment for thrombophilia after a thrombotic event should not be altered irrespective of the presence or absence of most thrombophilia risk factors. It is recommended that thrombophilia testing be offered to patients with a first VTE < than 50 years of age, recurrent VTE, VTE at any age with a strong family history of thrombotic disease and VTE occurring in unusual sites such as hepatic, mesenteric, portal and cerebral veins. It is also recommended testing be offered to women suffering VTE in association with pregnancy, the immediate postpartum period, or oral contraceptive use. Most pediatric VTE are associated with indwelling catheters and/or underlying medical conditions, including congenital heart disease, inflammation, immobilization, thrombophilia or malignancy. Portal vein thrombosis is associated with umbilical venous catheter placement in neonates and is likely very common. Other thrombotic conditions in neonates include purpura fulminans, renal vein thrombosis and cerebral sinovenous thrombosis. Deep vein thrombosis is the most common presentation of VTE in children and indwelling catheterization is the most common trigger factor. Congenital heart disease predisposes to both venous and arterial thrombosis, especially in shunting lesions and those requiring catheterization, surgery and/or ECMO. Arterial thrombosis is uncommon in pediatrics and is nearly always associated with arterial trauma or catheterization. In cases of thrombophilia the goal of therapy should be rapid restoration of blood flow to reduce late effects. For treatment of VTE most children receive either six weeks to six months of therapeutic anticoagulation. Tissue plasminogen activator (tPA) is utilized for thrombolysis of venous or arterial thrombi that are life, limb or organs threatening. Antiplatelet agents are used in pediatrics to prevent arterial thrombosis or thrombosis associated with congenital heart disease. Patients with cancer with a central venous catheter and factor V Leiden mutation have a higher risk of developing catheter-related thrombosis. Severe thrombophilia might increase the risk of thrombosis in Covid-19 patients.