PSU Volume 65 No 01 JULY 2025

Gastroschisis: Length of Stay

Gastroschisis, a congenital abdominal wall defect where fetal intestines herniate through an opening beside the umbilicus, poses significant management challenges despite overall low mortality. Among the most pressing concerns for healthcare providers is the length of hospital stay (LOS), particularly in cases of uncomplicated or "simple" gastroschisis. Prolonged LOS not only increases healthcare costs but also reflects delayed recovery, posing increased risks for complications such as infections, growth failure, and delayed developmental support. Over the last decade, multiple studies have aimed to identify factors associated with prolonged LOS and propose evidence-based strategies to shorten it while maintaining safe and effective care. This article synthesizes findings from six pivotal studies to examine how different surgical approaches, feeding strategies, and clinical variables affect LOS in neonates with gastroschisis.

A 2017 study by Mansfield et al. laid early groundwork by demonstrating the effectiveness of a quality improvement (QI) initiative focused on protocolizing the care of neonates with uncomplicated gastroschisis. Their institution introduced standardized feeding guidelines, pain control protocols, and silo management strategies, which resulted in a reduction in median LOS from 34 to 29 days. Notably, the QI protocol did not dictate specific surgical techniques but focused on systemic consistency—minimizing variability between providers, which they identified as a major driver of prolonged hospitalization. This early evidence suggested that standardizing care practices could substantially reduce LOS without additional risk to patients.


Subsequent studies built on these findings by examining the role of specific clinical and demographic variables. A 2021 study by Komic et al. employed multivariate regression modeling to assess 31 potential predictors of LOS in a cohort of 73 neonates with simple gastroschisis. Key findings included that earlier time to silo placement and prolonged use of total parenteral nutrition (TPN) were both associated with increased LOS, while female sex, exposure to human milk, and earlier passage of stool were associated with shorter stays. Importantly, the need for nasogastric feeding at discharge was linked to a reduction of 7 days in LOS, highlighting the complex interplay between enteral feeding readiness and discharge timing.


Complementing this, Lin et al. (2021) took a unique approach by evaluating the specific impact of failed primary closure—a condition where surgeons attempt but cannot perform immediate abdominal wall closure, necessitating silo placement afterward. Their retrospective analysis revealed that neonates who failed primary closure experienced significantly longer LOS and delayed initiation of enteral feeds compared to those who successfully underwent primary repair. This finding underscored that failed closure is not merely a technical surgical issue but a strong clinical marker of disease severity and predictor of prolonged recovery.


In a broader population analysis, Bajinting et al. (2022) utilized the ACS NSQIP-P database to evaluate 888 patients with simple gastroschisis. They found that infants discharged within 30 days were more likely to have higher birth weights, older gestational ages, and fewer postoperative complications. On multivariate analysis, prematurity and low birth weight remained the most significant predictors of prolonged LOS. While these findings may appear intuitive, the strength of the NSQIP-P database lies in its large, multi-institutional scope, confirming trends previously observed in smaller cohorts and adding weight to the predictive value of these variables.


Meanwhile, a study by Utria et al. (2022) offered practical insights into how feeding advancement strategies impact LOS and overall hospital costs. By comparing neonates undergoing feed advancement at 10 ml/kg/day versus 20 ml/kg/day, the researchers demonstrated that the faster advancement protocol resulted in significantly shorter LOS (30 vs. 36 days), earlier achievement of goal feeds, and fewer days on TPN. Although the difference in total cost was only marginally statistically significant, the clinical outcomes clearly favored the more aggressive advancement strategy. These findings add to a growing body of literature challenging the historically conservative approach to feeding in gastroschisis and suggest that earlier, faster enteral nutrition can be both safe and beneficial.


Finally, the most recent and expansive study, published in 2025 by Cabacungan et al., returned to the NSQIP-P data to analyze national trends in LOS across a decade. This study revealed a clear downward trend in median LOS for simple gastroschisis cases, from 30 to 25 days over ten years. The authors attributed this decline to improvements in prenatal counseling, surgical timing, and feeding practices, as well as wider adoption of standardized protocols. Their multivariate analysis identified prematurity, need for transfusion, and nutritional support at discharge (e.g., TPN) as the strongest predictors of extended LOS. Interestingly, while race and birth location (inborn vs. outborn) showed shifting trends over time, they did not independently predict LOS once clinical variables were controlled for.


Together, these six studies form a coherent narrative: LOS in gastroschisis is modifiable. Factors that consistently predict longer hospitalization include prematurity, low birth weight, complex postoperative courses (such as failed primary closure or need for prolonged TPN), and delayed feeding tolerance. Conversely, practices that reduce LOS include standardization of care, successful primary repair, early introduction of human milk, faster feeding advancement, and avoidance of postoperative complications.


A striking commonality among the studies is the emphasis on system-level changes—particularly protocolization—as key levers for reducing LOS. Despite advances in surgical techniques, most studies report that improvements in outcomes have more to do with coordination, consistency, and timely multidisciplinary care than with any single procedural innovation.


In conclusion, gastroschisis remains a significant neonatal surgical challenge, but LOS—an important quality metric—can be improved with thoughtful, evidence-based interventions. As national databases continue to expand and refine our understanding of gastroschisis outcomes, the path forward seems increasingly clear: earlier feeding, successful primary closure, and above all, the implementation of structured, standardized care pathways across institutions. These strategies not only improve efficiency and reduce costs but also enhance the overall patient experience, bringing neonates home sooner and safer.

References:
1- Mansfield SA, Ryshen G, Dail J, Gossard M, McClead R, Aldrink JH: Use of quality improvement (QI) methodology to decrease length of stay (LOS) for newborns with uncomplicated gastroschisis. J Pediatr Surg. 53(8):1578-1583, 2018
2-Lin S, Stephens C, Cunningham A, Hamilton N: Failure of primary closure predicts prolonged length of stay in gastroschisis patients. Pediatr Surg Int. 37(1):77-83. 2021
3- Komic SR, Walters KC, Aderibigbe F, Srinivasa Rao ASR, Stansfield BK: Estimating Length of Stay for Simple Gastroschisis. J Surg Res. 260:122-128, 2021
4- Utria AF, Wong M, Faino A, Jacobson E, Javid PJ: The role of feeding advancement strategy on length of stay and hospital costs in newborns with gastroschisis. J Pediatr Surg. 57(3):356-359, 2022
5- Bajinting A, Sutthatarn P, Osei H, Abraham ASM, Villalona GA: Predictors of length of stay for simple gastroschisis: analysis of ACS NSQIP-P database. Pediatr Surg Int. 38(10):1371-1376, 2022
6- Cabacungan ET, Wagner AJ, Gupta R: Decreasing Length of Stay for Simple Gastroschisis: Analysis of the National Surgical Quality Improvement Program (NSQIP). J Pediatr Surg. 60(5):162262, 2025

Transitional Zone Pull-Through

The treatment of Hirschsprung disease (HD) centers on surgical removal of the aganglionic segment of bowel and reconstruction with normally ganglionated colon. However, the existence of a "transition zone" (TZ)—a morphologically ganglionated but functionally abnormal segment of intestine that lies between the aganglionic and normoganglionic bowel—poses a persistent challenge. Resection of this segment is crucial, yet often incomplete, leading to what is referred to as a transition zone pull-through (TZPT). This complication is implicated in persistent postoperative obstructive symptoms and has historically driven the need for redo surgeries. Despite growing recognition, defining, identifying, and managing the TZ remains inconsistent across institutions and pathologists.


The histopathologic definition of the TZ lacks standardization. Criteria typically include partial circumferential aganglionosis, myenteric hypoganglionosis, and hypertrophy of submucosal nerves. Each of these features may present alone or in combination, contributing to the difficulty of intraoperative identification. For example, partial circumferential aganglionosis may involve a significant portion of the bowel wall, often more than one-eighth of the circumference, and is best visualized in transverse sections. Longitudinal or seromuscular biopsies are frequently inadequate to detect these features, leading to misidentification of bowel as normoganglionic. Myenteric hypoganglionosis presents as thin, underdeveloped ganglia lacking neuropil, which can be easily missed or misinterpreted. Submucosal nerve hypertrophy, defined in some studies as the presence of two or more nerves =40 µm in diameter per high-power field, is subject to age and location variability, further complicating its interpretation.


Recent histological studies underscore the importance of examining full-thickness transverse sections of the proximal resection margin to detect TZ features. Data suggests that the TZ can extend up to 10 cm in some patients, though the average length is closer to 2.6–5 cm in cases of rectosigmoid HD. Therefore, surgical resection that begins at least 5 cm proximal to the last biopsy with ganglion cells has become the de facto recommendation to minimize risk of TZPT. However, this strategy is complicated by the variable circumferential involvement and longitudinal extent of TZ histology, which are not always apparent intraoperatively.


Postoperative consequences of TZPT include persistent constipation, enterocolitis, and overall impaired bowel function. Yet, emerging evidence questions whether these outcomes are strictly attributable to retained TZ tissue. A recent study comparing postoperative complications in patients with normoganglionic neorectum (NNR) versus TZ neorectum (TZNR) found no significant difference in rates of Hirschsprung-associated enterocolitis (HAEC) or constipation. Similarly, long-term outcomes, including quality of life and need for interventions such as laxatives or botulinum toxin, were comparable between TZPT patients treated conservatively and those undergoing redo surgery. These findings challenge the dogma that any presence of TZ at the anastomotic site is necessarily pathologic.


Adding to this complexity is the phenomenon of postoperative remodeling. Glut1-positive submucosal nerve hypertrophy, previously considered a hallmark of retained TZ, has been identified in neorectal biopsies of patients whose primary resections were histologically complete. This suggests that nerve remodeling—possibly due to reinnervation or adaptation—occurs post-surgery and may mimic TZ histology. It complicates the interpretation of postoperative biopsies and raises concerns about over-diagnosing TZPT in patients with nonspecific symptoms.


While some centers advocate for aggressive surgical strategies to ensure complete resection of the TZ—including intraoperative frozen sections and extended resection margins—many pathology reports still lack clear documentation of TZ features at the proximal margin. A study reviewing pathology reports from 35 institutions found that most did not state whether TZ histology was present at the surgical margin. Intraoperative frozen sections were performed in only 23% of cases, and even when TZ features were evident histologically, they were frequently not reported. These gaps in communication contribute to clinical uncertainty and may delay or misguide postoperative management.


To mitigate the risk of TZPT and its complications, consensus guidelines recommend several practices: (1) full-circumference, full-thickness transverse biopsies at the proximal resection margin; (2) frozen section evaluation of the margin intraoperatively; and (3) explicit reporting of TZ features, including quantification of ganglion cell density, nerve hypertrophy, and circumferential involvement. Importantly, pathologists must be trained to recognize age-related and location-specific variations in innervation to avoid over-diagnosis.


The implications of TZPT reach beyond immediate surgical outcomes. Functional morbidity, including impaired continence and social limitations, can persist into adolescence and adulthood. Redo surgery, while potentially curative, carries increased risk for fecal incontinence and other complications. Thus, an individualized approach—considering the severity of symptoms, histologic findings, and patient/family preferences—is increasingly favored.


In summary, TZPT remains a significant and nuanced concern in the surgical management of HD. The interplay of anatomical ambiguity, histological complexity, and variable clinical outcomes calls for a multidisciplinary strategy integrating surgical expertise, robust pathology protocols, and long-term functional follow-up. As understanding of the TZ matures, efforts must focus on refining diagnostic criteria, improving intraoperative practices, and distinguishing histologic from functional pathology to optimize outcomes for patients with HD.

References:
1- Kapur RP, Kennedy AJ: Transitional zone pull through: surgical pathology considerations. Semin Pediatr Surg. 21(4):291-301, 2012
2- Kapur RP, Arnold MA, Conces MR, Ambartsumyan L, Avansino J, Levitt M, Wood R, Mast KJ: Remodeling of rectal innervation after pullthrough surgery for Hirschsprung disease: relevance to criteria for the determination of retained transition zone. Pediatr Dev Pathol. 21(6):1-12, 2018
3- Tomuschat C, Mietzsch S, Dwertmann-Rico S, Clauditz T, Schaefer H, Reinshagen K: The Length of the Transition Zone in Patients with Rectosigmoid Hirschsprung Disease. Children (Basel). 9(2):152, 2022
4- Torre LD, Domínguez A, Arnold M, Lovell M, Martínez D, Bischoff A, Wehrli L: Histological transitional zone pull-through in Hirschsprung disease. Postoperative functional results and current recommendations. Bol Med Hosp Infant Mex. 80(6):331-338, 2023
5- Beltman L, Labib H, Ahmed H, Benninga M, Roelofs J, van der Voorn P, van Schuppen J, Oosterlaan J, van Heurn E, Derikx J: Transition Zone Pull-through in Patients with Hirschsprung Disease: Is Redo Surgery Beneficial for the Long-term Outcomes? J Pediatr Surg. 58(10):1903-1909, 2023
6- Xu TO, Levitt MA, Feng C: Controversies in Hirschsprung surgery. World J Pediatr Surg. 7(3):e000887, 2024
7- Kapur RP, Prasad V, Srinivas S, Thomas E, Wood R, Smith C: Diagnosis and Prevention of Transition Zone Pull-through in Patients With Hirschsprung Disease. Arch Pathol Lab Med. 2025 Mar 11. doi:10.5858/arpa.2024-0429-OA.

Paronychia

Paronychia in children, though common, presents with a spectrum of causes, clinical behaviors, and treatment responses that set it apart from adult cases. Pediatric paronychia is typically classified as either acute or chronic, depending on the duration of symptoms. Acute cases often arise due to direct trauma to the nail folds—frequently from nail biting, finger sucking, or minor injuries from daily activities. Chronic paronychia, by contrast, tends to involve long-standing inflammation and is frequently complicated by repeated exposure to irritants and colonization by fungi such as Candida albicans.


Bacterial infection, particularly with Staphylococcus aureus, including methicillin-resistant strains (MRSA), remains the most common cause of acute paronychia in children. However, the microbiologic profile in pediatric populations may differ from adults due to unique behaviors like oral manipulation of fingers. This habit not only introduces skin flora but also oral anaerobes, contributing to a more diverse polymicrobial environment. Studies have shown that about half of pediatric paronychia infections may involve mixed aerobic and anaerobic bacteria. The presence of oral-derived organisms like Eikenella corrodens underscores the distinct etiologic pathways often involved in children.


One reported case of neonatal paronychia highlighted the interplay of self-soothing behaviors in a child with neonatal abstinence syndrome, which led to MRSA infection in both the second and third digits. Treatment required not only incision and drainage but also systemic antibiotic therapy. The episode underscores a broader concern—young children and infants, including neonates, are capable of developing paronychia under specific circumstances that involve repeated trauma to the nail bed or surrounding soft tissue.


Epidemiological studies reveal that paronychia and similar hand infections are among the most common pediatric hand surgery emergencies. A retrospective review of pediatric patients treated in emergency settings found that infections like paronychia represented over a quarter of all hand-related surgical cases. These infections occurred primarily at home and were most frequent among younger children, especially those under the age of six. This demographic pattern supports the hypothesis that immature motor control, high physical activity levels, and limited awareness of risk contribute significantly to the development of nail fold infections in this population.


Diagnosis is predominantly clinical, based on the presence of pain, erythema, and swelling of the nail folds. The accumulation of pus or fluctuant swelling often indicates abscess formation, which necessitates drainage. Laboratory studies, such as wound cultures, are helpful in guiding antibiotic therapy, especially when empiric treatment fails or MRSA is suspected. Radiographs may be warranted when there is suspicion of foreign bodies, fractures, or if osteomyelitis cannot be ruled out.


Management typically begins conservatively in early stages without abscess formation, using warm soaks and empiric oral antibiotics with gram-positive coverage. However, once abscess formation is evident, surgical drainage becomes the mainstay of therapy. In most pediatric cases, drainage combined with antibiotics yields rapid resolution. Common antibiotic choices include amoxicillin-clavulanate or clindamycin, with linezolid or trimethoprim-sulfamethoxazole used for MRSA coverage. Severe infections or cases in hospitalized children may require intravenous therapy, including vancomycin.


Beyond routine bacterial infections, chemotherapy-associated paronychia is an emerging concern in pediatric populations, especially as targeted cancer therapies become more common in children. Drugs like selumetinib, a MEK inhibitor approved for pediatric neurofibromatosis-related tumors, are associated with a high incidence of nail toxicity. Pediatric patients appear to have a higher susceptibility to paronychia from such agents compared to adults. The mechanism is believed to be related to both the cytotoxic effects of the drugs on epithelial cells and the mechanical trauma children experience more frequently due to higher physical activity.


Treating paronychia in children receiving chemotherapy is further complicated by the limitations of standard pharmacologic options. While doxycycline may be used in adults for its anti-inflammatory effects, it is contraindicated in young children. Instead, agents like azithromycin are considered more suitable alternatives, though definitive pediatric treatment protocols are still lacking. Preventive strategies, including minimizing nail trauma and improving caregiver education about nail care and hygiene, are critical but sometimes difficult to enforce in this population without affecting quality of life.


Finally, chronic paronychia in children is a distinct clinical entity. It often involves prolonged inflammation, with secondary colonization by fungal species. Unlike acute infections, chronic cases require a combination of antifungal therapy, environmental modifications to limit moisture and irritant exposure, and sometimes topical steroids to reduce inflammation. It is important to differentiate chronic paronychia from recurrent acute infections or other mimickers like herpetic whitlow, which may present similarly but require entirely different approaches.


Overall, paronychia in children demands tailored diagnostic and management strategies that account for their unique anatomical, behavioral, and immunologic characteristics. Effective treatment depends not just on resolving the immediate infection but also on preventing recurrence through behavioral guidance, environmental modification, and in certain cases, long-term therapeutic planning—particularly in children with underlying conditions or immunocompromise. As clinical awareness of the diverse presentations and challenges of pediatric paronychia grows, so too must research into evidence-based, pediatric-specific treatment protocols that address both common and rare forms of this deceptively simple but potentially serious condition.

References:
1- Grome L, Borah G. Neonatal Acute Paronychia: Hand (N Y). 12(5):NP99-NP100, 2017
2- Dizin F, Saab M, Mézel A, Guerre E, Chantelot C: Epidemiology of pediatric hand surgery emergencies. Retrospective study of 245 patients seen over 10 months in two referral centers. Orthop Traumatol Surg Res. 108(1):103067, 2022
3- McKean AR, Williams GJ, Macneal P, Moore LS, Idowu A, Milroy C: Paediatric paronychia: A single centre retrospective, microbiological analysis and national survey. J Plast Reconstr Aesthet Surg. 75(7):2387-2440, 2022
4- Borgia P, Piccolo G, Diana MC, Viglizzo G. Chemotherapy-associated paronychia: Do not forget the children. J Am Acad Dermatol. 88(1):e59, 2023
5- Macneal P, Milroy C: Paronychia Drainage. In: StatPearls

PSU Volume 65 No 02 AUGUST 2025

Bronchial Atresia

Bronchial atresia is a rare congenital condition marked by the interruption of a bronchial segment, most often at the segmental or subsegmental level. This interruption leads to the accumulation of mucus in the obstructed bronchial stump—referred to as a bronchocele or mucocele—and hyperinflation of the distal lung parenchyma. This hyperinflation occurs due to collateral ventilation from nearby alveoli, as air enters the obstructed segment through pores of Kohn, canals of Lambert, or channels of Martin, but cannot exit efficiently. The segment becomes overinflated and may appear more lucent on radiographs, often prompting further evaluation. Although the condition is typically discovered incidentally, particularly in adolescents and young adults, it can also present with recurrent pulmonary infections, dyspnea, cough, hemoptysis, or even pneumothorax.


Computed tomography has become the gold standard for diagnosing bronchial atresia. Radiographically, the condition often appears as a perihilar mass with adjacent hyperlucency. On high-resolution CT, hallmark findings include a branching or tubular mucocele with surrounding emphysematous lung. The characteristic "finger-in-glove" sign is frequently observed due to mucoid impaction within a dilated bronchus. In a study reviewing 23 confirmed cases, every patient exhibited both a mucocele and hyperinflation of the surrounding parenchyma. These findings were consistently unilateral, most commonly affecting the apicoposterior segment of the left upper lobe, followed by the right lower and upper lobes. Additional findings such as subsegmental atelectasis, bronchial wall thickening, and small cysts may occur, though less frequently.


Histologically, bronchial atresia reveals a blind-ending bronchus filled with mucus, surrounded by hyperinflated alveoli. There is typically no acute inflammation unless secondary infection has occurred. Pathological examination of surgical specimens frequently confirms emphysematous change, mucus plugging, and bronchiectasis. Occasionally, the lesion coexists with other congenital lung anomalies such as congenital pulmonary airway malformation (CPAM), bronchopulmonary sequestration, and lobar emphysema. These associations suggest a common developmental pathway or timing in embryogenesis, although precise causative mechanisms remain speculative.


There is considerable debate regarding the management of bronchial atresia, particularly in asymptomatic individuals. While some centers advocate for surgical resection even in asymptomatic patients to prevent long-term complications such as infection or damage to adjacent lung tissue, others favor a conservative approach with careful monitoring. A pediatric cohort followed over a median of 29 months demonstrated that conservative management could be safe and effective in selected patients. Of the 12 children monitored without surgery, only one became symptomatic during follow-up. This finding supports the position that surgery should be reserved for patients who develop significant symptoms or complications.


In contrast, adult cases are more likely to be managed surgically, especially if there is diagnostic uncertainty or persistent symptoms. Surgical intervention can include lobectomy, segmentectomy, or wedge resection, depending on the extent and location of the lesion. Recent advances in thoracoscopic techniques have made minimally invasive resection a viable and often preferred option. Case reports of thoracoscopic sublobar resections in adults have shown good outcomes, with resolution of symptoms such as cough, recurrent fever, or dyspnea. Importantly, three-dimensional CT reconstruction has emerged as a valuable tool in surgical planning by clearly delineating the absence of bronchial branches and helping define resection margins.


Operative data from adult cases indicate that thoracoscopic resection is safe, with minimal blood loss and short hospital stays. Common postoperative complications include air leaks and minor pneumothorax, typically managed conservatively. Histologic analysis after surgery often confirms the diagnosis and may reveal additional findings such as infection, bronchiectasis, or associated anomalies. In one surgical series, 5 out of 8 patients had postoperative complications, all of which were minor and resolved with conservative measures. This supports the notion that while surgery carries some risk, it is generally well tolerated and often curative in symptomatic patients.


Despite its rarity, bronchial atresia may be underrecognized. Improved imaging technology has led to more frequent incidental discoveries, particularly during evaluation for unrelated conditions. The diagnostic process relies heavily on high-resolution imaging, and in some cases, bronchoscopy may aid in detecting a blind-ending bronchus. However, a normal bronchoscopy does not rule out bronchial atresia, especially if the lesion is peripheral. Clinical awareness and radiologic expertise are essential for accurate diagnosis and appropriate treatment planning.


Given the association of bronchial atresia with other congenital pulmonary abnormalities, a multidisciplinary approach is often beneficial. Radiologists, pulmonologists, thoracic surgeons, and pediatric specialists must collaborate to determine the best course of action for each patient. In children and adolescents, conservative management with structured follow-up can be effective, particularly in asymptomatic cases. In adults or patients with recurrent infections or significant functional impairment, surgical resection remains the standard of care.


Ultimately, bronchial atresia represents a spectrum of clinical presentations, from benign incidental findings to complex symptomatic cases requiring surgical intervention. The decision to operate must balance the risks of surgery with the potential for disease progression or complications. Long-term prognosis is excellent in most cases, whether managed conservatively or surgically. However, close clinical monitoring and patient education are critical, especially for those who forgo surgical treatment. Early recognition and individualized management strategies offer the best outcomes for patients with this uncommon but important congenital anomaly.

References:
1- Wang Y, Dai W, Sun Y, Chu X, Yang B, Zhao M: Congenital bronchial atresia: diagnosis and treatment. Int J Med Sci. 9(3):207-12, 2012
2- Traibi A, Seguin-Givelet A, Grigoroiu M, Brian E, Gossot D: Congenital bronchial atresia in adults: thoracoscopic resection. J Vis Surg. 3:174, 2017
3- Puglia EBMD, Rodrigues RS, Daltro PA, Souza AS Jr, Paschoal MM, Labrunie EM, Irion KL, Hochhegger B, Zanetti G, Marchiori E: Tomographic findings in bronchial atresia. Radiol Bras. 54(1):9-14, 2021
4- Zarfati A, Voglino V, Tomà P, Cutrera R, Frediani S, Inserra A: Conservative management of congenital bronchial atresia: The Bambino Gesù children's hospital experience. Pediatr Pulmonol. 56(7):2164-2168, 2021
5- Hutchison MJ, Winkler L: Bronchial Atresia. 2023 Jun 26. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan–.
6- Samejima H, Ose N, Nagata H, Funaki S, Shintani Y: Thoracoscopic sublobar resection for congenital bronchial atresia in adults: a report of three cases. Gen Thorac Cardiovasc Surg Cases. 14;2(1):92, 2023
7- Pasqua N, Bresesti I, Zirpoli S, Ghezzi M, Gentilino V, Pederiva F: CONGENITAL BRONCHIAL ATRESIA: TO SURGICALLY TREAT OR CONSERVATIVELY MANAGE? A SYSTEMATIC REVIEW. J Pediatr Surg. 16:162368, 2025

Nutcracker Syndrome

Nutcracker Syndrome (NCS) in children presents a diagnostic and therapeutic challenge due to its nonspecific symptoms, varied clinical presentation, and lack of standardized criteria. Despite its rarity, recent studies offer increasing insight into its pathophysiology, diagnostic approaches, and treatment strategies.


NCS refers to the compression of the left renal vein (LRV), most commonly between the aorta and the superior mesenteric artery (SMA)—a configuration termed anterior NCS. Less commonly, the LRV may be compressed posteriorly between the aorta and vertebral column, or even have dual compression in cases of vascular anomalies like circumaortic veins. In pediatric populations, anterior NCS is overwhelmingly dominant. Compression results in renal venous hypertension, leading to the development of collateral venous pathways and subsequent clinical symptoms.


The most frequent presenting symptom in children is hematuria, observed in approximately 55% of cases, followed closely by proteinuria in nearly half of patients. Both microscopic and macroscopic hematuria have been documented, with the former often discovered incidentally. Flank pain is less common, found in roughly one in five cases, despite being traditionally associated with the syndrome. These symptoms are believed to arise from venous hypertension causing rupture of small varices in the renal collecting system, or from immune-mediated mechanisms triggered by abnormal venous flow. Additionally, fatigue, orthostatic intolerance, and dizziness have been linked to autonomic nervous system involvement.


Orthostatic proteinuria in children is often attributed to positional changes affecting renal hemodynamics. A compelling finding is the role of a low body mass index (BMI), which reduces mesenteric fat that otherwise supports the SMA, increasing the likelihood of renal vein compression. Some studies even suggest resolution of symptoms with weight gain, supporting a conservative approach in many pediatric patients.


Diagnostically, Doppler ultrasonography (DUS) is the frontline noninvasive tool, favored for its accessibility and safety. In pediatric NCS, peak velocity ratios of the LRV between the aortomesenteric and hilar portions greater than 4.7 to 5.0 are considered indicative. However, the technique is operator-dependent and may yield variable results in children due to patient cooperation and anatomical factors.


Cross-sectional imaging like computed tomography angiography (CTA) and magnetic resonance angiography (MRA) adds anatomical detail. MRA, in particular, offers a radiation-free alternative with high accuracy in assessing the SMA angle and LRV compression. In one study, pediatric NCS patients had a significantly lower SMA angle (mean ~26.5°) and a smaller aortomesenteric distance (~3.3 mm) compared to controls, reinforcing MRA's diagnostic utility.


Invasive studies, such as venography with pressure gradient measurement, are considered the gold standard but are reserved for ambiguous or refractory cases due to their invasiveness. They are more often used in surgical candidates, especially when conservative management fails after extended monitoring.


Treatment in children is typically conservative. The literature consistently supports this approach, with more than 86% of pediatric cases managed non-surgically and nearly 95% of these showing symptom resolution or improvement. Conservative management includes observation, weight gain, and, in some cases, pharmacologic therapy like angiotensin-converting enzyme inhibitors to manage associated orthostatic symptoms.


Surgical interventions, including LRV transposition, renal autotransplantation, and endovascular stenting, are reserved for persistent or severe cases, particularly when complications such as varicocele, pelvic congestion, or progressive pain are evident. However, their application in children is limited due to long-term risks, including stent migration and the potential need for reintervention.


Autonomic dysfunction in NCS has recently gained attention. A case-control study demonstrated that over half of the pediatric patients experienced orthostatic symptoms, primarily dizziness and fatigue. Holter monitoring revealed altered heart rate variability, suggestive of autonomic imbalance. These findings reinforce the systemic implications of LRV compression beyond renal manifestations.


Despite growing research, the overall quality of pediatric NCS studies remains limited, with most evidence derived from case reports or small case series. This hampers the establishment of standardized diagnostic algorithms and outcome benchmarks. Nevertheless, the literature increasingly emphasizes a diagnostic pathway beginning with DUS, followed by MRA when needed, and cautious use of invasive diagnostics. A trial of conservative treatment with close follow-up is generally endorsed before considering surgical options.


In conclusion, Nutcracker Syndrome in children is a multifaceted condition marked by variable symptoms, often subtle or nonspecific, and requiring a tailored approach. High clinical suspicion, especially in cases of unexplained hematuria or proteinuria, is key. Noninvasive imaging remains central to diagnosis, and most cases can be managed without surgery. However, ongoing research is essential to clarify its natural history, refine diagnostic criteria, and optimize management strategies, especially in symptomatic or refractory cases.

References:
1- Nalcacioglu H, Ceyhan Bilgici M, Tekcan D, Genc G, Bostanci Y, Yakupoglu YK, Sarikaya S, Ozkaya O: Nutcracker Syndrome in Children: Role of Doppler Ultrasonographic Indices in Detecting the Pattern of Symptoms. J Clin Med. 7(8):214, 2018
2- Agarwal A, Litra F, Barr LL: A Rare Cause of Abdominal and Flank Pain in Children: Nutcracker Syndrome. Cureus. 13(7):e16422, 2021
3- Kolber MK, Cui Z, Chen CK, Habibollahi P, Kalva SP: Nutcracker syndrome: diagnosis and therapy. Cardiovasc Diagn Ther. 11(5):1140-1149, 2021
4- Atasoy D, Cansu A, Bekirçavusoglu AF, Özdogan EB, Ahmetoglu A: The utility of magnetic resonance angiography in children with nutcracker syndrome. Turk J Med Sci. 51(5):2396-2402, 2021
5- Meyer J, Rother U, Stehr M, Meyer A: Nutcracker syndrome in children: Appearance, diagnostics, and treatment - A systematic review. J Pediatr Surg. 57(11):716-722, 2022
6- Dönmez YN, Koksoy AY, Bako D, Giray D, Epcacan S: Autonomic Disturbances in Children with Nutcracker Syndrome: A Case Control Study. Indian Pediatr. 61(12):1114-1118, 2024

Hypertrophied Nerves in Hirschsprung's Disease

Hypertrophied nerves play a pivotal role in the diagnosis and understanding of Hirschsprung's disease (HD), serving as both a diagnostic hallmark and a reflection of the underlying neuroanatomical disruption. HD is defined by the congenital absence of ganglion cells in the distal bowel, with submucosal nerve hypertrophy often emerging as a secondary hallmark due to the proliferation of extrinsic cholinergic nerves in the aganglionic segment.


The histological triad—absence of ganglion cells, presence of hypertrophic nerves, and abnormal acetylcholinesterase (AChE) activity—remains the gold standard for diagnosis. However, the role and reliability of hypertrophied nerves have been subject to scrutiny and evolution across studies.


A key point established in one 2016 study is that hypertrophied nerve fibers (defined as >40 µm in diameter) are not uniformly present in all cases of HD. Particularly in long-segment HD and total colonic aganglionosis, as well as in neonates and premature infants, hypertrophy may be absent. The study found that the absence of hypertrophied nerve fibers in an aganglionic biopsy predicted a transition zone proximal to the rectosigmoid colon, with a specificity of 77.3%. This highlights that while nerve hypertrophy supports the diagnosis, its absence—especially when combined with aganglionosis—may suggest a more extensive disease and requires further attention in surgical planning.


Another study from 2023 emphasizes the relationship between hypertrophic nerves and the transition zone (TZ), a histopathologically abnormal yet ganglionated segment located between aganglionic and normal bowel. Histological markers of TZ include submucosal nerve hypertrophy, myenteric hypoganglionosis, and partial aganglionosis. The identification of hypertrophied nerves within the TZ suggests that this region is not only histologically abnormal but may also be functionally compromised. Surgical precision in identifying the proximal extent of the TZ is crucial, as residual TZ tissue post-surgery may lead to obstructive symptoms.


Calretinin immunohistochemistry (IHC) has become an increasingly favored adjunct in identifying ganglion cells and evaluating the TZ. Recent studies demonstrate calretinin's reliability in clearly distinguishing aganglionic from ganglionic bowel. Notably, the 2024 Heidelberg study reports that switching from AChE histochemistry to calretinin IHC improved diagnostic confidence, reduced the need for repeat biopsies, and enabled earlier definitive surgical intervention. The strength of calretinin IHC lies in its consistent staining patterns and independence from patient age—a critical advantage over AChE staining, which is unreliable in neonates due to immature cholinergic innervation.


The role of calretinin is further emphasized in a 2021 institutional review, which demonstrated that calretinin staining was always positive in the presence of ganglion cells and always negative in aganglionic samples, regardless of nerve hypertrophy or biopsy depth. This underscores its utility not only in diagnosis but also in evaluating whether hypertrophied nerves correspond to functional abnormalities, as hypertrophy alone does not equate to pathology if ganglion cells are present and calretinin is positive.


More recent developments in digital pathology and artificial intelligence are enhancing diagnostic accuracy. A 2023 study introduced deep learning models capable of detecting ganglion cells and hypertrophic nerves in histological slides with over 90% accuracy. This AI-based approach aids in standardizing diagnosis, reducing interobserver variability, and identifying TZ features such as coexisting ganglion cells and hypertrophied nerves—regions requiring extra scrutiny due to potential functional compromise.


However, challenges remain. A 2023 study reviewing inconclusive full-thickness biopsies found that re-evaluation using both hematoxylin and eosin (HE) and IHC resolved only a fraction of the inconclusive cases, with most remaining non-diagnostic. This points to persistent ambiguity in the histopathological criteria and the need for more robust, perhaps integrative, diagnostic protocols combining histology, IHC, AI, and clinical context.


Additionally, the concept of the "shore break" (SB)—an endoscopic marker for the transition from peristaltic to non-peristaltic bowel—was recently correlated with the histopathological TZ. A 2023 surgical pathology study demonstrated that in all examined cases, the SB coincided with histologic features of the TZ, including nerve hypertrophy. This finding offers a functional correlate to histologic abnormalities and suggests a potentially valuable intraoperative tool for guiding resection margins.


In practice, hypertrophied nerves alone are insufficient for diagnosis without correlating evidence of aganglionosis. Their diagnostic value increases when viewed alongside absent ganglion cells and other markers like calretinin negativity or AChE activity. Moreover, while hypertrophy is a common feature in classic HD, its absence—particularly in certain subtypes or younger infants—should prompt consideration of disease extent and histologic variants rather than immediately excluding HD.


In conclusion, hypertrophied nerves in HD represent both a diagnostic clue and a histologic signature of the abnormal neurodevelopment that defines the disease. Their presence, distribution, and relationship to ganglion cells must be interpreted in the broader context of age, disease subtype, biopsy technique, and staining method. Advances in IHC and AI tools continue to refine this interpretive framework, but the complexity of HD pathology demands continued vigilance, multidisciplinary communication, and tailored surgical decision-making to ensure optimal outcomes.

References:
1- Narayanan SK, Soundappan SS, Kwan E, Cohen RC, Charlton A, Cass DT: Aganglionosis with the absence of hypertrophied nerve fibres predicts disease proximal to rectosigmoid colon. Pediatr Surg Int. 32(3):221-6, 2016
2- Zemheri E, Engin Zerk P, Ulukaya Durakbasa C: Calretinin immunohistochemical staining in Hirschsprung's disease: An institutional experience. North Clin Istanb. 31;8(6):601-606, 2021
3- Matsukuma K, Gui D, Saadai P: Hirschsprung Disease for the Practicing Surgical Pathologist. Am J Clin Pathol. 159(3):228-241, 2023
4- Yasui Y, Kido M, Nakamura K, Kuwahara T, Hirotani T, Tamura R, Kumagai M, Shimasaki M, Yamada S, Okajima H: The Junction Between the Peristaltic and Non-peristaltic Bowel (Shore Break) is Found in the Transition Zone in Hirschsprung's Disease. J Pediatr Surg. 58(11):2160-2164, 2023
5- Korsager LEH, Bjørn N, Ellebæk MB, Christensen LG, Qvist N: Full-Thickness Rectal Biopsy in Children Suspected of Having Hirschsprung's Disease: The Inconclusive Biopsy. Children (Basel). 10(10):1619, 2023
6- Duci M, Magoni A, Santoro L, Dei Tos AP, Gamba P, Uccheddu F, Fascetti-Leon F: Enhancing diagnosis of Hirschsprung's disease using deep learning from histological sections of post pull-through specimens: preliminary results. Pediatr Surg Int. 40(1):12, 2023
7- Romero P, Burger A, Wennberg E, Schmitteckert S, Holland-Cunz S, Schwab C, Günther P: Clinical Relevance of Pathological Diagnosis of Hirschsprung's Disease with Acetylcholine-Esterase Histochemistry or Calretinin Immunohistochemistry. Children (Basel). 11(4):428, 2024

PSU Volume 65 No 03 SEPTEMBER 2025

Tracheal Agenesis

Tracheal agenesis (TA) is a rare, usually fatal congenital anomaly characterized by the partial or complete absence of the trachea, often first evident at birth when the neonate presents with respiratory failure, cyanosis, and an inability to be intubated. Despite being known for over a century, tracheal agenesis remains poorly understood, underdiagnosed prenatally, and difficult to manage surgically. With fewer than a few hundred cases reported globally, recent literature continues to illuminate its varied presentations, classifications, embryological origins, diagnostic challenges, and rare instances of surgical intervention.


The estimated incidence of TA is approximately 1 in 50,000 live births, with a 2:1 male predominance. Mortality remains high, approaching 100% in some series. Floyd's classification, introduced in 1962, delineates TA into three anatomical types based on the presence and connectivity of the distal trachea and bronchi. Type I involves agenesis of the proximal trachea with the distal trachea connecting to the esophagus via a fistula. Type II, the most common variant, shows complete absence of the trachea with the carina or fused bronchi connected directly to the esophagus. Type III presents with each main bronchus arising independently from the esophagus. A more granular classification, proposed by Faro, expands this into seven subtypes, incorporating more nuanced embryological failures.


TA often coexists with other congenital anomalies. As described in multiple cases, patients frequently present with anomalies falling under the VACTERL association: vertebral, anorectal, cardiac, tracheoesophageal, renal, and limb defects. Cardiac anomalies such as atrial septal defects, patent ductus arteriosus, or double superior vena cava, along with genitourinary anomalies like horseshoe kidney or bilateral hydronephrosis, are often observed. Trisomy 18 has also been associated with TA, pointing to a possible genetic contribution in certain cases.


Embryologically, TA results from aberrations in the division of the foregut into the trachea and esophagus. The formation of the tracheoesophageal septum, necessary for the separation of the respiratory and digestive tracts, is disrupted, resulting in a spectrum of abnormalities from isolated agenesis to complex fistulization. In Floyd type II TA, the respiratory bud fails to elongate or differentiate, while in type I, partial elongation may occur with secondary fistula formation. The coexistence of tracheoesophageal or bronchoesophageal fistulas is more than an anatomic curiosity—it can be temporarily lifesaving, allowing ventilation through the esophagus.


Diagnosis of TA is rarely made prenatally. Antenatal ultrasonography may suggest esophageal atresia or TA through indirect signs such as polyhydramnios, a dilated upper esophageal pouch, and non-visualization of the stomach. In more severe cases, congenital high airway obstruction syndrome (CHAOS) may present, characterized by echogenic enlarged lungs, flattened diaphragms, and absence of fluid-filled airways. Fetal MRI can help identify a blind-ending airway, but in practice, these modalities are underutilized, and diagnosis typically occurs postnatally under emergent conditions.


At birth, neonates with TA often present in severe respiratory distress, silent crying, and cyanosis. Standard intubation attempts fail, and mask ventilation offers little relief unless a fistula is present. Esophageal intubation may inadvertently ventilate the lungs via a tracheoesophageal fistula and is often the only temporizing measure. This phenomenon is repeatedly documented and suggests that if TA is suspected—especially in the setting of failed intubation—esophageal intubation should be intentionally attempted.


Computed tomography (CT), particularly when performed with controlled ventilation, is essential in delineating airway anatomy. In the absence of spontaneous tracheal aeration, ventilation through the esophagus can allow visualization of bronchial anatomy and fistulas. Cases using this approach have successfully classified the type of TA and provided data essential for surgical planning. However, these scans are often conducted only after initial stabilization, which may be too late in many cases.


Surgical repair of TA remains highly experimental and carries significant risk. In rare, reported survivors, complex reconstructive procedures have included esophageal "trachealization," wherein the esophagus is used to substitute for the absent trachea, sometimes supported with external stents or splints. The success of such procedures hinges on several factors: type of TA, presence and anatomy of fistulas, the patient's size and overall health, and the availability of multidisciplinary care. Centers in Japan have pioneered strategies involving staged reconstructions—initially creating a cervical esophagostomy for ventilation, followed by eventual gastrointestinal reconstruction using interposed bowel segments.


Even when surgical repair is technically successful, complications such as infection, poor pulmonary compliance, or neurologic insult from prolonged hypoxia can compromise outcomes. In several case reports, despite achieving surgical airway continuity, infants succumbed postoperatively to systemic complications or multiorgan failure. These experiences emphasize the critical importance of early diagnosis and careful case selection for surgical intervention.


In terms of management frameworks, tracheal agenesis underscores the need for a well-coordinated multidisciplinary response. Teams must include neonatologists, pediatric surgeons, otolaryngologists, cardiothoracic surgeons, radiologists, geneticists, and palliative care specialists. With the advent of technologies such as high-resolution CT, ECMO, and even 3D-printed airway scaffolds, there is cautious optimism that survival could improve for select cases.


However, the ethical and medical challenges remain profound. The natural history of TA is one of high lethality, and the decision to pursue aggressive surgical therapy must be balanced with the infant's quality of life, likelihood of meaningful survival, and presence of additional anomalies. In numerous cases, parents declined postmortem examinations, leaving gaps in anatomical understanding that could have informed future care.


Despite its rarity, tracheal agenesis is a powerful example of the limits of neonatal resuscitation and the importance of recognizing rare congenital anomalies early. From airway management innovations to pioneering reconstructive efforts, each case expands the frontier of what may be possible—but also what should be considered reasonable and humane. Emerging diagnostic tools and surgical strategies may incrementally improve prognosis, but the condition remains one of the most formidable challenges in neonatal medicine.


In conclusion, TA demands heightened clinical suspicion, especially in neonates with respiratory failure and failed intubation attempts. Prenatal imaging, when available and interpreted with attention to subtle signs, can aid early recognition. Postnatal stabilization may be possible through esophageal ventilation in the presence of fistulas. Though surgical survival is rare, evolving techniques and interdisciplinary collaboration continue to reshape possibilities in the management of this devastating condition.

References:
1- Demircan M, Aksoy T, Ceran C, Kafkasli A: Tracheal agenesis and esophageal atresia with proximal and distal bronchoesophageal fistulas. J Pediatr Surg. 43: E1–E3, 2008
2- Bryant R 3rd: Tracheal agenesis: Salvaging the unsalvageable. J Thorac Cardiovasc Surg. 153(6):e127, 2017
3- Cristallo Lacalamita M, Fau S, Bornand A, Vidal I, Martino A, Eperon I, Toso S, Rougemont AL, Hanquinet S: Tracheal agenesis: optimization of computed tomography diagnosis by airway ventilation. Pediatr Radiol. 48(3):427-432, 2018
4- Darouich S, Masmoudi A: Tracheal Agenesis with Bronchoesophageal Fistula. N Engl J Med. 384(9):e27, 2021
5- Akhter AP, Donn SM: The challenging airway: Tracheal agenesis in the newborn. J Neonatal Perinatal Med. 15(3):663-665, 2022
6- Walton S, Rogers D: Tracheal Reconstruction. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan–, 2022
7- Wu YH, Hsiao CH, Chen YL, Tsai LY, Mu SC: Rare type of tracheal agenesis: Unexpected presentation and immediate consideration of emergent esophageal intubation in neonatal resuscitation program. Case reports and review of the literature. Pediatr Pulmonol. 2024 Jun;59(6):1757-1764, 2024

Pharyngeal Perforation in Newborns

Pharyngeal perforation in newborns is a rare but serious medical complication, typically resulting from medical procedures such as feeding tube insertion, intubation, or pharyngeal suctioning. Although infrequent, this injury poses significant risks, especially to premature and very low birth weight (VLBW) infants, whose fragile anatomy makes them more susceptible to trauma. A review of six reported cases and clinical experiences reveals consistent patterns in causes, diagnosis, presentation, and treatment that help clinicians better understand and manage this delicate condition.


The primary cause of pharyngeal perforation in neonates is iatrogenic trauma—unintentional injury from medical interventions. Even standard procedures like placing an orogastric (OG) or nasogastric (NG) feeding tube can cause mucosal tears if performed without adequate caution. Premature infants, particularly those under 1500 grams, are especially at risk due to the narrowness of their pharyngoesophageal junction and the lack of protective muscular tone. In some instances, hyperextension of the neck during the procedure increases the likelihood of injury. The injury often goes unnoticed at the time of the procedure and only becomes apparent later through signs of respiratory distress, feeding difficulties, or unusual radiographic findings.


One case involved a full-term newborn with no apparent complications at birth who later developed severe respiratory distress. Imaging eventually revealed a large retropharyngeal air collection caused by a hypopharyngeal perforation from initial intubation and suctioning. Despite the initial mystery surrounding the respiratory symptoms, further evaluation with neck CT and contrast studies clarified the diagnosis. The injury resolved with conservative care—no surgical intervention was required.


Three other infants, all extremely premature and weighing under 1,200 grams, presented with complications following pharyngeal suctioning or feeding tube placement. In each situation, the cause was a mechanical injury to the upper gastrointestinal tract—either a feeding catheter embedding in the esophageal wall or suction catheter repeatedly striking the same mucosal area.


Flexible endoscopy proved invaluable in these cases, allowing for direct visualization of the injury site and helping to guide safe re-placement of the feeding tube. In all three cases, treatment included cessation of tube feeding, intravenous antibiotics, and a period of bowel rest. All patients recovered fully.


In another report, a term infant undergoing rigid esophagoscopy for a suspected foreign body experienced a mucosal tear during the procedure. Though initially stable, the child developed fever and subcutaneous emphysema. A contrast study revealed periesophageal air, and the child was successfully managed with intravenous antibiotics and temporary discontinuation of oral feeding. This case emphasized that perforation symptoms may emerge hours or even days after the initial insult, and that subtle imaging findings can be pivotal for diagnosis.


A different infant, misdiagnosed with esophageal atresia and a tracheoesophageal fistula, was about to undergo unnecessary thoracic surgery when a careful esophagoscopy revealed a pharyngeal tear instead. A review of the chest radiographs showed the NG tube coiled at an unusual level, raising suspicions. The injury was managed non-surgically with antibiotics and cessation of feeding. The tear healed completely, and the child was discharged on day 13 of life in stable condition.


Seven more cases, all in the NICU setting, provided additional insights through a detailed pictorial analysis of radiographic findings. These included false lumens, retroesophageal air pockets, and perforations that extended into the pleural space. All patients were premature, and most weighed less than 750 grams. The common theme was again traumatic injury during tube insertion. In one particularly dramatic example, a feeding tube entered the right pleural space and caused a pneumothorax. Prompt recognition and chest tube placement resolved the issue. Radiographic signs such as aberrant catheter trajectory, air tracking in soft tissues, and unusual lucencies in the mediastinum served as critical diagnostic clues.


In a 29-year analysis of NICU records from a single institution, six VLBW infants out of over 2,000 were identified with iatrogenic pharyngoesophageal perforation. Most injuries occurred during the initial tube insertion, typically within minutes after birth. Three cases were initially mistaken for esophageal atresia due to resistance encountered during tube placement and the coiling or aberrant positioning of the tube on X-ray. Clinical symptoms included difficulty with tube insertion, bloody oral secretions, and increased salivation. Lateral radiographs and contrast studies revealed characteristic signs such as contrast pooling in the mediastinum or beaded tracts representing false lumens. Laryngoscopy helped confirm the location of the perforation in most patients.


Interestingly, none of the patients in this report required surgery. All were managed with antibiotics, temporary cessation of feeds, and in some cases, thoracentesis for pneumothorax. Feeding tubes were carefully reinserted under visualization, and all six infants survived with no long-term complications. The importance of early diagnosis was highlighted, as delayed recognition could lead to prolonged symptoms or even severe infections like mediastinitis.


Across all cases, the anatomical vulnerability of the pharyngoesophageal junction plays a central role. This area, just above the cricopharyngeal muscle, is not only the narrowest part of the upper digestive tract but also prone to injury when the neck is hyperextended—a common position during tube insertion. This explains the frequent occurrence of perforation at this specific site, particularly in premature infants.


Diagnosis remains challenging due to the non-specific nature of symptoms. Respiratory distress, excess oral secretions, failure to tolerate feeds, and vomiting are common but not definitive. Routine chest X-rays may be misleading or normal at first. Therefore, when clinical suspicion exists—especially if the NG or OG tube appears misdirected or coiled—additional imaging such as lateral radiographs, contrast esophagrams, and even CT may be necessary. Flexible endoscopy offers the most direct and reliable means of visualizing the injury and can also be used to guide subsequent safe interventions.


Treatment in most cases can be managed without surgery. Broad-spectrum antibiotics, bowel rest, and cautious refeeding under controlled circumstances form the cornerstone of therapy. Surgical drainage is rarely needed unless complications like abscesses or large pneumothoraces develop. The overall prognosis is good when the condition is recognized and treated early.


In sum, pharyngeal perforation in newborns, though rare, is an important clinical entity that all neonatal and pediatric care providers must be prepared to recognize and manage. The key takeaways are:

• Iatrogenic perforations often occur during routine procedures like NG/OG tube insertion or suctioning.

• Premature and VLBW infants are at the highest risk due to anatomical and physiological vulnerabilities.

• Early diagnosis is essential and relies heavily on imaging and endoscopy.

• Conservative management is highly effective, especially when initiated promptly.

• Prevention is best achieved through gentle technique, proper training, and verification of tube placement via imaging.


Raising awareness, improving procedural safety, and maintaining a high index of suspicion for iatrogenic injuries can significantly improve outcomes and reduce unnecessary surgical interventions in this vulnerable population.

References:
1- Barlev DM, Nagourney BA, Saintonge R: Traumatic retropharyngeal emphysema as a cause for severe respiratory distress in a newborn. Pediatr Radiol. 33(6):429-32, 2003
2- Soong WJ: Endoscopic diagnosis and management of iatrogenic cervical esophageal perforation in extremely premature infants. J Chin Med Assoc. 70(4):171-5, 2007
3- Baum ED, Elden LM, Handler SD, Tom LW: Management of hypopharyngeal and esophageal perforations in children: three case reports and a review of the literature. Ear Nose Throat J. 87(1):44-7, 2008
4- Knight RB, Webb DE, Coppola CP: Pharyngeal perforation masquerading as esophageal atresia. J Pediatr Surg. 44(11):2216-8, 2009
5- Wolf JA, Myers EH, Remon JI, Blumfield E: Imaging findings of iatrogenic pharyngeal and esophageal injuries in neonates. Pediatr Radiol. 48(12):1806-1813, 2018
6- Eguchi S, Hisaeda Y, Ukawa T, Koto M, Hosokawa M, Tsurisawa C, Takeda T, Amagata S, Nakao A: Clinical Features of iatrogenic Pharyngo-esophageal perforation in very low birth weight infants. Pediatr Neonatol. 66(1):25-30, 2025

Endoscopic Balloon Dilation for Gastric Outlet Obstruction

Endoscopic balloon dilation (EBD) has emerged as a meaningful, often underutilized, option in the management of gastric outlet obstruction (GOO) in pediatric patients. Historically considered a domain of surgical intervention, pediatric GOO has seen a paradigm shift toward minimally invasive endoscopic approaches. This transition has been driven by both the evolution of endoscopic tools and a growing body of case-based evidence supporting the safety and efficacy of EBD in carefully selected children.


GOO in children encompasses a diverse range of etiologies, each with unique pathophysiological mechanisms. While infantile hypertrophic pyloric stenosis (IHPS) is the most well-known cause in neonates, older children can present with GOO due to peptic ulcer disease, caustic ingestion, congenital antral webs, NSAID-induced ulcers, and post-surgical strictures. The clinical hallmark across these etiologies remains consistent: persistent non-bilious vomiting, poor weight gain, early satiety, and signs of gastric retention.


In select cases, such as peptic ulcer-induced pyloric stenosis or post-ingestion injury, the primary process involves inflammation followed by fibrosis and cicatrization. These strictures are typically short and amenable to endoscopic dilation. The rationale for EBD in such scenarios is clear: it targets the mechanical obstruction without the need for extensive surgical disruption.


The technique involves the use of through-the-scope (TTS) balloon catheters, which are inserted over a guidewire and positioned under endoscopic and often fluoroscopic visualization. Gradual inflation of the balloon to target diameters—typically between 8 and 15 mm—permits controlled radial expansion of the narrowed lumen. In children, balloon sizes and inflation pressures must be calibrated carefully due to the anatomical constraints and fragility of the tissues involved.


A series of reports has documented favorable outcomes with EBD. For example, children with corrosive GOO, especially those resulting from acid ingestion (like hydrochloric acid-based toilet cleaners), have shown substantial improvement following serial dilations. Typically performed over several weeks, the stepwise approach helps avoid perforation and permits tissue remodeling. In these cases, some physicians combine EBD with intralesional steroid injections (e.g., triamcinolone) to further inhibit fibrotic re-narrowing.


Similarly, NSAID-induced pyloric strictures in children have responded well to EBD. In one reported case, a 7-year-old developed GOO following concurrent ibuprofen and aspirin therapy for an upper respiratory infection. After initial stabilization and acid suppression therapy, multiple EBD sessions restored pyloric patency and resolved the obstructive symptoms without need for surgical correction.


Another compelling scenario for EBD is in the treatment of congenital antral webs—thin mucosal diaphragms that occlude the distal stomach. These lesions, while rare and often misdiagnosed, can be visualized directly during endoscopy, and successfully treated with dilation alone. Long-term follow-up in these patients often reveals sustained symptom resolution and normal growth trajectories, making a strong case for primary endoscopic therapy.


EBD also has demonstrated potential in managing complex or atypical cases, such as hypertrophic pyloric stenosis (HPS) beyond the infantile period. Although Ramstedt pyloromyotomy remains the gold standard for IHPS in infants, older children with delayed diagnosis or atypical presentations—such as those with comorbidities like Down syndrome—may benefit from EBD. In at least one documented case, a combination of endoscopic pyloromyotomy and balloon dilation proved effective in alleviating symptoms in a six-year-old with HPS who was not an ideal surgical candidate.


Despite these successes, several practical considerations remain. First, the need for repeat dilations is common. Inflammatory and fibrotic strictures may rebound after initial improvement, requiring careful follow-up and sometimes multiple procedures. Second, there is a modest risk of complications, including bleeding and perforation, especially when using larger balloon diameters or in areas of active ulceration. Nevertheless, most adverse events are self-limited, and the overall complication rate in pediatric EBD remains low when performed by experienced hands.


Endoscopic electrocauterization and steroid augmentation have been explored as adjuncts to balloon dilation. Electrocautery can weaken fibrotic bands or allow for controlled myotomy in cases of thickened tissue. Steroids, when injected intralesionally, may mitigate the inflammatory cascade and delay or prevent restenosis. These techniques, though promising, require further validation in pediatric cohorts but offer additional options for refractory cases.


In conclusion, endoscopic balloon dilation stands as a safe, effective, and repeatable alternative to surgery for a range of pediatric gastric outlet obstructions. While it is not universally applicable—long or angulated strictures, complex congenital anomalies, or malignancies still warrant surgical consideration—its role continues to grow with experience and technological advancement. With appropriate patient selection, skilled endoscopic technique, and rigorous follow-up, EBD can offer children relief from GOO while minimizing the trauma and recovery associated with operative interventions. For physicians managing such cases, EBD should no longer be viewed as experimental or secondary, but as a frontline therapeutic strategy in the right clinical context.

References:
1- Dehghani SM, Aldaghi M, Javaherizadeh H: Endoscopic pyloroplasty for severe gastric outlet obstruction due to alkali ingestion in a child. Gastroenterol Hepatol Bed Bench. 9(1):64-7, 2016
2- Andrade M, Sawamura R, Cupo P, Del Ciampo IR, Fernandes MI: Endoscopic Treatment of Gastric Outlet Obstruction Secondary to Accidental Acid Ingestion in a Child. J Pediatr Gastroenterol Nutr. 62(1):90-2, 2016
3- Chao HC: Update on endoscopic management of gastric outlet obstruction in children. World J Gastrointest Endosc. 8(18):635-645, 2016
4- Yokoyama S, Uyama S, Iwagami H, Yamashita Y: Successful combination of endoscopic pyloromyotomy and balloon dilatation for hypertrophic pyloric stenosis in an older child: A novel procedure. Surg Case Rep. 2(1):145, 2016
5- Ricciuto A, Connolly BL, Gonska T: Serial Balloon Dilation to Relieve Gastric Outlet Obstruction Induced by the Ingestion of Toilet Cleaner. J Pediatr Gastroenterol Nutr. 66(2):e56, 2018
6- Öztan MO, Güngör-Takes G, Çagan-Appak Y, Yildiz C, Karakoyun M, Baran M: Management of NSAID-related pyloric obstruction in a child using endoscopic balloon dilatation: A case report. Turk J Pediatr. 60(6):765-768, 2018
7- Peck J, Khalaf R, Marth R, Phen C, Sosa R, Cordero FB, Wilsey M: Endoscopic Balloon Dilation for Treatment of Congenital Antral Web. Pediatr Gastroenterol Hepatol Nutr. 21(4):351-354, 2018

PSU Volume 65 No 04 OCTOBER 2025

Gender Dysphoria

Gender dysphoria is the psychological distress experienced by individuals whose gender identity differs from the sex assigned at birth. It is not a matter of preference or rebellion against gender norms, but a profound incongruence that can result in significant emotional, psychological, and even physical suffering. In medical and psychiatric frameworks, this condition is carefully distinguished from gender nonconformity, which simply refers to behavior or appearance that doesn't match societal expectations of gender. Gender dysphoria specifically involves persistent distress that interferes with daily functioning and personal well-being.


Over time, understanding of gender dysphoria has evolved in both clinical settings and public discourse. The traditional binary of male and female has given way to a recognition of gender as a spectrum. This shift has opened up a broader lens through which to examine the experiences of transgender and gender-diverse individuals. With greater social visibility has come increased access to gender-affirming care and more nuanced therapeutic options, particularly for adolescents and young adults.


The growing demand for gender-affirming treatments has revealed a complex clinical landscape. In pediatric cases, early diagnosis and intervention can be crucial, especially during puberty, when physical changes may exacerbate distress. Pubertal suppression using GnRH analogues has become a common intervention. This treatment halts the development of secondary sex characteristics, giving young people time to explore their gender identity without the added burden of unwanted physical changes. It is often followed by cross-sex hormone therapy to induce the characteristics of the affirmed gender.


Despite its utility, pubertal suppression is not without controversy. Supporters view it as a compassionate and effective way to mitigate psychological suffering and reduce the need for future surgeries. Opponents raise concerns about the long-term impact on brain development, fertility, and psychological maturity. There is also debate over the adequacy of informed consent, particularly in cases involving minors.


Surgical interventions—commonly referred to as gender-affirming surgeries—represent another dimension of care for individuals with gender dysphoria. These procedures may involve chest reconstruction, genital surgeries, or facial feminization/masculinization. The decision to undergo surgery is deeply personal and typically follows an extended period of psychological and medical evaluation. While not all individuals with gender dysphoria pursue surgery, for many, these interventions offer a significant reduction in distress and a path toward alignment between body and identity.


Long-term outcome data on gender-affirming surgery remain limited but are growing. The available evidence indicates sustained improvements in mental health, self-image, and quality of life. A 40-year follow-up study of individuals who underwent such surgeries showed high satisfaction rates, improved body congruence, and significantly reduced levels of psychological comorbidity, including depression and suicidal ideation. Importantly, there were no reported regrets among participants, challenging the narrative that these procedures are frequently regretted or reversed.


Still, a portion of individuals who transition later choose to detransition. This does not necessarily invalidate gender-affirming care but does highlight the need for comprehensive psychological assessments and long-term follow-up. Reasons for detransition vary widely—from dissatisfaction with medical outcomes, to shifts in identity, to external pressures such as social rejection. Some individuals also report that their gender dysphoria was initially misattributed and later recognized as a symptom of trauma, mental illness, or internalized homophobia. These cases underscore the importance of differentiating gender dysphoria from other psychological conditions and ensuring that interventions are tailored to each individual's specific needs.


The concept of gender fluidity adds another layer to the discourse. Increasingly, people identify outside of the male/female binary—describing themselves as nonbinary, genderqueer, genderfluid, or agender. These identities challenge the medical model that often presumes a clear destination in gender transition. For some, partial transition—such as hormone therapy without surgery—provides enough relief from dysphoria. For others, social transition alone is sufficient. This variability in treatment paths reinforces the need for an individualized, patient-centered approach.


Multidisciplinary care is now widely recognized as the gold standard in managing gender dysphoria. Optimal outcomes are achieved when mental health professionals, endocrinologists, surgeons, and primary care providers collaborate closely. This team-based approach helps ensure that medical interventions are clinically appropriate and aligned with the patient's goals. It also provides a support network that can address the psychosocial challenges many individuals face during transition.


Pediatric care presents its own set of challenges. Prevalence of gender dysphoria in children and adolescents appears to be rising, driven in part by greater awareness and social acceptance. At the same time, questions remain about how to distinguish between transient gender exploration and persistent dysphoria. Some children who exhibit gender nonconformity in early childhood do not go on to experience dysphoria in adolescence or adulthood. For this reason, current best practices emphasize careful monitoring and gradual intervention, reserving medical treatments for those with clearly established and enduring dysphoria.


The evolving understanding of gender identity has also reshaped diagnostic criteria. The DSM-5 redefined gender dysphoria to focus on distress rather than identity per se, shifting away from pathologizing gender variance. The ICD-11 went even further, removing gender incongruence from the mental health category altogether and reclassifying it under sexual health. These changes reflect a broader cultural and medical recognition that being transgender is not, in itself, a disorder.


This shift has practical implications. It reduces stigma, facilitates insurance coverage, and supports the legitimacy of gender-affirming care. At the same time, it requires healthcare systems to adapt—training providers, updating protocols, and expanding access to services. For pediatricians, who often serve as the first point of contact, this means taking on a more active role in coordinating care, educating families, and advocating for young patients.


In all this, consent and informed decision-making remain critical. Whether the patient is a minor or an adult, the decision to initiate treatment should be based on a thorough understanding of the risks, benefits, and alternatives. This includes consideration of how treatment may impact fertility, future sexual function, and mental health. For minors, parental involvement is usually essential, but care must also respect the autonomy and evolving capacity of the adolescent.


Ultimately, gender dysphoria is a deeply personal and often complex experience. There is no single narrative or treatment pathway that fits all individuals. For some, medical transition offers profound relief and an opportunity to live authentically. For others, non-medical strategies are sufficient. And for a few, the journey includes detransition and reflection. The common thread is the need for respectful, evidence-based, and flexible care that centers the experiences and goals of the individual.


As the field continues to grow, further research is essential. Long-term studies are needed to assess the safety and efficacy of current interventions, identify predictors of positive outcomes, and understand the experiences of detransitioners. Ethical questions about autonomy, consent, and the role of medicine in shaping identity must be openly discussed. In the meantime, providers must navigate these complexities with humility, compassion, and a commitment to helping each patient find their own path toward well-being.

References:
1- Hembree WC, Cohen-Kettenis PT, Gooren L, Hannema SE, Meyer WJ, Murad MH, Rosenthal SM, Safer JD, Tangpricha V, T'Sjoen GG: Endocrine Treatment of Gender-Dysphoric/Gender-Incongruent Persons: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 102(11):3869-3903, 2017
2- Selvaggi G, Salgado CJ, Monstrey S, Djordevic M: Gender Affirmation Surgery. Biomed Res Int. 8 Jul 5;2018:1768414, 2018
3- Mahfouda S, Moore JK, Siafarikas A, Hewitt T, Ganti U, Lin A, Zepf FD: Gender-affirming hormones and surgery in transgender children and adolescents. Lancet Diabetes Endocrinol. 7(6):484-498, 2019
4- Claahsen-van der Grinten H, Verhaak C, Steensma T, Middelberg T, Roeffen J, Klink D: Gender incongruence and gender dysphoria in childhood and adolescence—current insights in diagnostics, management, and follow-up. Eur J Pediatr. 180(5):1349-1357, 2021
5- Littman L. Individuals Treated for Gender Dysphoria with Medical and/or Surgical Transition Who Subsequently Detransitioned: A Survey of 100 Detransitioners. Arch Sex Behav. 50(8):3353-3369 2021
6- Park RH, Liu YT, Samuel A, Gurganus M, Gampper TJ, Corbett ST, Shahane A, Stranix JT: Long-term Outcomes After Gender-Affirming Surgery: 40-Year Follow-up Study. Ann Plast Surg. 89(4):431-436, 2022
7- Micangeli G, Profeta G, Colloridi F, Pirro F, Tarani F, Ferraguti G, Spaziani M, Isidori AM, Menghi M, Fiore M, Tarani L: The role of the pediatrician in the management of the child and adolescent with gender dysphoria. Ital J Pediatr. 49(1):71, 2023

Adenocarcinoma of Intestine

Adenocarcinoma of the intestine in the pediatric population is an exceedingly rare malignancy, accounting for only a small fraction of childhood cancers and an even smaller proportion of gastrointestinal (GI) tract tumors in individuals under 18 years of age. Despite its rarity, it is a clinically important entity due to its aggressive course, delayed diagnosis, and poor prognosis compared to many other pediatric malignancies. Across multiple retrospective series and international registry analyses, the scarcity of cases has historically limited robust characterization, yet a growing body of literature—including large-scale, multicenter datasets—now provides valuable insight into its epidemiology, presentation, histopathologic features, treatment approaches, and prognostic factors.


Data from Korea represent one of the most comprehensive contemporary series, encompassing 80 pediatric patients diagnosed with adenocarcinoma between 1995 and 2016 from 10 hospitals nationwide. The median age at diagnosis was 15 years (range, 10–17), with a slight male predominance (46.3% male overall). Approximately 30% had either a family history of cancer or a predisposing underlying condition. The distribution of primary tumor sites was heavily weighted toward the gastrointestinal tract, with the colon and rectum being the most common location (40%), followed by the stomach (18.8%) and, far less frequently, the small bowel (1.3%). Non-GI primaries included ovarian (22.5%), lung, urinary bladder, and several other organs.


The Korean cohort revealed a striking pattern of late-stage diagnosis. Over half of all cases (54.8%) presented with stage III or IV disease at diagnosis, but this was more pronounced in GI tumors, where nearly 90% were advanced-stage compared to less than half of non-GI tumors. Symptom duration before diagnosis varied, but for GI primaries, abdominal pain, bowel obstruction, vomiting, and gastrointestinal bleeding were the most common initial complaints. In non-GI tumors, symptomatology reflected the involved organ or was discovered incidentally.


Treatment in children largely mirrors that in adults, relying on surgical resection for local disease control. In the Korean series, surgery was often complemented by chemotherapy, particularly in advanced-stage cases. Radiotherapy was rare and reserved for specific non-abdominal sites or metastatic palliation. Despite aggressive multimodal therapy, the outcomes for pediatric GI adenocarcinoma were distinctly worse than for non-GI adenocarcinoma. The five-year overall survival rate for GI tumors was only 44.7%, compared to 78.8% for non-GI adenocarcinoma. Among GI sites, colorectal primaries showed somewhat better survival than gastric or small bowel primaries, but even these lagged significantly behind non-GI outcomes.


One of the most robust prognostic markers identified in the Korean study was the pre-treatment carcinoembryonic antigen (CEA) level. Patients with CEA levels above 3 ng/mL had a dismal five-year survival rate of only 23.8%, compared to 69.3% in those with normal CEA. This marker retained its prognostic significance in multivariate analyses, suggesting utility in both diagnosis and follow-up.


Findings from other international series support and broaden the Korean observations. Pediatric colorectal adenocarcinoma, while the most common GI site, still presents with advanced-stage disease in 60–80% of cases, a pattern distinct from adult colorectal cancer where screening programs and higher symptom awareness lead to earlier detection. Histologically, mucinous, and signet-ring cell subtypes are overrepresented in children, both of which carry poorer prognoses. Similar histopathologic patterns are seen in gastric adenocarcinoma of childhood, which is extremely rare—case series in the English literature seldom exceed five patients—and is almost uniformly diagnosed at stage IV.


Small bowel adenocarcinoma (SBA), although accounting for only 1–2% of pediatric GI adenocarcinoma cases in Korea, has been more extensively studied in adult and mixed-age cohorts, offering insight into its biology. Large retrospective studies, such as a multicenter analysis of over 1,700 patients in the SEER database, demonstrate that SBA is aggressive, with a tendency for early lymphatic spread. Prognosis is heavily stage-dependent, with five-year survival rates ranging from over 80% in localized disease to below 15% in metastatic cases. In children, where diagnosis is often delayed due to nonspecific symptoms and the anatomic inaccessibility of the small bowel, stage migration toward advanced disease is likely. Data from an Iranian series of small bowel tumors—though predominantly adult—showed median survival of just 12 months for adenocarcinoma, with tumor grade emerging as the only independent prognostic factor. Poorly differentiated (grade 3) tumors had significantly worse survival than well- or moderately differentiated lesions.


Recent advances in staging refinement have potential relevance for pediatric SBA as well. The international development and validation of a novel Tumor, Log Odds of Positive Lymph Nodes, and Metastasis (TLM) staging system has demonstrated improved prognostic discrimination over the conventional TNM classification. This is particularly pertinent in emergent pediatric cases, where adequate lymph node harvest (=17 nodes) is rarely achieved due to urgent surgery for obstruction or perforation. The TLM system, by incorporating the log odds of positive lymph nodes (LODDS), maintains predictive accuracy even when fewer nodes are retrieved, offering a potentially valuable tool for better risk stratification in children.


Treatment principles for pediatric intestinal adenocarcinoma emphasize complete surgical excision with adequate margins and lymphadenectomy where feasible. In localized disease, surgery remains the only potentially curative modality. Adjuvant chemotherapy, typically fluoropyrimidine-based regimens, is extrapolated from adult protocols and used in node-positive disease or high-risk node-negative disease. In metastatic presentations, systemic chemotherapy may offer palliation and, rarely, long-term remission, though pediatric-specific evidence is minimal. The role of targeted therapies and immunotherapy is virtually unexplored in children, though molecular profiling may eventually identify subgroups with actionable alterations.


The uniformly poor prognosis in advanced pediatric GI adenocarcinoma underscores the critical need for earlier diagnosis. This is complicated by the rarity of the disease, the nonspecificity of early symptoms, and the low index of suspicion among clinicians for carcinoma in a child. The Korean data highlight that nearly one-third of patients had either a relevant family history or an underlying condition predisposing to malignancy, suggesting that targeted surveillance in such populations could be beneficial. In adults, hereditary cancer syndromes such as Lynch syndrome, familial adenomatous polyposis, and Peutz–Jeghers syndrome confer elevated risks for GI adenocarcinomas, including small bowel primaries; whether similar genetic predispositions play a role in pediatric cases is plausible but incompletely characterized.


Collectively, these data suggest a multifaceted approach to improving outcomes: heightened awareness among pediatricians and gastroenterologists for persistent abdominal symptoms, even in the absence of classic red flags; genetic counseling and testing in children with suggestive personal or family histories; aggressive surgical management where feasible; and adaptation of adult-based adjuvant chemotherapy regimens to pediatric physiology. Incorporating prognostic tools such as CEA levels and refined staging systems like TLM could further individualize treatment planning.


In conclusion, adenocarcinoma of the intestine in children, though rare, is a highly aggressive malignancy with distinct clinical and pathologic features compared to adult disease. The Korean multicenter series—the largest of its kind—confirms the predominance of GI primaries, the overwhelming tendency toward late-stage diagnosis, the poor survival outcomes in GI compared to non-GI adenocarcinomas, and the prognostic value of elevated CEA. Supplementary evidence from international datasets on small bowel adenocarcinoma refines understanding of prognostic factors, especially lymph node assessment and tumor grade, and supports emerging staging innovations. Future progress will depend on early recognition strategies, improved access to specialized surgical and oncologic care, and collaborative research to adapt evolving adult treatment paradigms to the unique context of pediatric disease.

References:
1- Digoy GP, Tibayan F, Young H, Edelstein P: Adenocarcinoma of the rectum with associated colorectal adenomatous polyps in tuberous sclerosis: a case report. J Pediatr Surg. 35(3):526-7, 2000
2- Ibele AR, Koplin SA, Slaughenhoupt BL, Kryger JV, Friedl A, Lund DP: Colonic adenocarcinoma in a 13-year-old with cystic fibrosis. J Pediatr Surg. 42(10):E1-3, 2007
3- Schrock AB, Devoe CE, McWilliams R, Sun J, Aparicio T, Stephens PJ, Ross JS, Wilson R, Miller VA, Ali SM, Overman MJ: Genomic Profiling of Small-Bowel Adenocarcinoma. JAMA Oncol. 3(11):1546-1553, 2017
4- Ahn CH, Kim SC: Two case reports: Colorectal adenocarcinoma in children. Medicine (Baltimore). 96(46):e8074, 2017
5- Taghipour Zahir S, Heidarymeybodi Z, AleSaeidi S: Prognostic Factors and Survival Time in Patients with Small Bowel Tumors: A Retrospective Observational Study. Int J Surg Oncol. 2019:2912361, 2019
6- Yang HB, Namgoong JM, Kim KH, Kim DY, Park J, Shin HB, Youn JK, Lee S, Lee JW, Jung SE, Chung JH, Choe YM, Heo TG, Ho IG, Kim HY: Pediatric Adenocarcinoma in Korea: A Multicenter Study. Cancer Res Treat. 52(1):117-127, 2020
7- Dai ZH, Wang QW, Zhang QW, Yan XL, Aparicio T, Zhou YY, Wang H, Zhang CH, Zaanan A, Afchain P, Zhang Y, Chen HM, Gao YJ, Ge ZZ: Personalized four-category staging for predicting prognosis in patients with small bowel Adenocarcinoma: an international development and validation study. EBioMedicine. 60:102979, 2020

Appendiceal Stump Leak

Appendiceal stump leak is a rare but serious complication following appendectomy, particularly in laparoscopic procedures. Although appendectomy is widely regarded as a routine and safe surgery, the consequences of a compromised closure at the appendiceal base can be profound. The leak represents a failure of containment at the surgical site, often resulting in peritonitis, intra-abdominal abscess, sepsis, and prolonged hospitalization. While the incidence remains low, the clinical impact is significant enough to warrant close attention to technique, risk assessment, and postoperative monitoring.


At the heart of this complication lies the method of stump closure. During appendectomy—especially when approached laparoscopically—the surgeon must ensure the base of the appendix is securely sealed. In uncomplicated cases, this is typically achieved through the application of ligatures such as endoloops or intracorporeal knots. However, when the tissue is inflamed, necrotic, or gangrenous, the risk of inadequate closure increases. Poor tissue quality at the base, coupled with suboptimal technique or tool failure, can result in leakage of enteric contents into the abdominal cavity.


A wide array of closure techniques exists. Some surgeons favor traditional ligatures due to their cost-effectiveness and familiarity. Others opt for mechanical solutions such as endoscopic staplers, titanium clips, or polymer-based devices. In resource-limited settings, handmade suture loops or invaginating stitches may be preferred. The decision often comes down to the clinical scenario, the surgeon's experience, and the tools at hand. Nevertheless, no universal consensus exists regarding a superior method. Each technique offers its own advantages and drawbacks, particularly when confronted with complex appendicitis involving perforation or abscess formation.


Clinical evidence offers a mixed view. In systematic comparisons between mechanical closure methods and ligatures, no statistically significant difference in overall postoperative complications has been consistently demonstrated. Nonetheless, staplers often yield shorter operative times and reduced wound infection rates, especially in pediatric patients. One analysis suggested that wound infection rates were nearly halved when staplers were used instead of endoloops. This benefit was most pronounced in cases of simple appendicitis, though less conclusive in complex or perforated scenarios. Still, cost remains a limiting factor for widespread stapler use, particularly in public or rural hospitals where financial constraints guide surgical decision-making.


The tissue condition at the time of surgery is a crucial determinant of outcome. Inflammation at the base of the appendix can impair suture integrity, increase friability, and reduce the holding capacity of any closure technique. When the appendiceal base is compromised, a transfixing suture or invagination technique may offer a more secure seal by reinforcing the stump through burying it into the cecum wall. This method, though more time-consuming, has demonstrated reliable outcomes in both adult and pediatric populations when used judiciously. However, it demands a higher level of technical skill and may not be suitable for all surgical teams.


In cases where stump leak does occur, presentation is often within the first few days postoperatively. Patients may present with fever, abdominal pain, ileus, or signs of peritoneal irritation. In some instances, feculent discharge may be observed at the wound site, particularly in cases where a fistula has formed. Diagnostic imaging, especially contrast-enhanced computed tomography, is instrumental in identifying leaks, abscesses, or fistulous tracts. Prompt recognition is essential, as delays in diagnosis increase the risk of systemic infection and organ failure.

Management of appendiceal stump leaks depends on the severity and containment of the leak. In well-contained, low-output fistulas with no signs of diffuse peritonitis, conservative treatment may suffice. This includes bowel rest, intravenous fluids, broad-spectrum antibiotics, and close clinical monitoring. However, in most cases—particularly those involving pediatric patients, high-output fistulas, or generalized peritonitis—surgical intervention is necessary. Re-exploration may reveal an obvious defect in the stump, requiring debridement and secure re-ligation. In some cases, burying the stump or even performing a limited resection of the cecum may be required. Intra-abdominal drains are often placed to control contamination and monitor output. Early reoperation, although invasive, is associated with better outcomes than prolonged conservative treatment in unstable patients.


Pediatric cases present their own nuances. Children often present later in the course of illness, with more advanced disease at the time of surgery. As such, the incidence of perforation and gangrene is higher, which elevates the risk of stump complications. Moreover, the anatomical features of the pediatric appendix and cecum make certain closure methods less practical. In children, careful selection of closure technique, often favoring staplers or invaginating sutures, becomes particularly important. Furthermore, the psychological burden on families and the potential for growth-related complications make timely and effective resolution of stump leaks a pediatric priority.


In examining the broader literature, some observational studies have suggested that polymer or metal clips may perform as well as more expensive staplers in select cases. However, clips are not recommended when the base diameter exceeds one centimeter or when inflammation compromises clip grip. Misapplication or dislodgement of clips has been implicated in several reported stump leaks, underlining the importance of matching technique to the surgical context.


The reality remains that no technique guarantees immunity from stump complications. Even when best practices are followed, unpredictable variables such as patient anatomy, tissue response, or unrecognized injury to adjacent bowel can contribute to leakage. What does emerge consistently across studies is the critical role of meticulous surgical technique. Surgeons must ensure adequate visualization, gentle tissue handling, and thorough assessment of the stump before concluding the procedure. When doubt exists regarding the reliability of a closure method, switching to a more robust technique or converting to open surgery should not be delayed.


Overall, while appendiceal stump leak is a relatively rare occurrence, its implications are significant. It exposes the patient to additional surgeries, prolonged recovery, increased healthcare costs, and in some cases, long-term morbidity. Prevention remains the best strategy, rooted in sound surgical judgment and appropriate technique selection. As the field evolves and technology advances, newer devices may offer enhanced sealing options. Until then, the best defense against stump leak remains a thoughtful, individualized approach that respects both the science and the art of surgery.

References:
1- Safavi A, Langer M, Skarsgard ED. Endoloop versus endostapler closure of the appendiceal stump in pediatric laparoscopic appendectomy. Canadian Journal of Surgery. 55(1):37–41, 2012
2- Mayir B, Ensari CO, Bilecik T, Aslaner A, Oruç MT. Methods for closure of appendix stump during laparoscopic appendectomy procedure. Ulusal Cerrahi Dergisi. 31(4):229–231, 2015
3- Mannu GS, Sudul MK, Bettencourt-Silva JH, Cumber E, Li F, Clark AB, Loke YK. Closure methods of the appendix stump for complications during laparoscopic appendectomy: a systematic review. Cochrane Database of Systematic Reviews. Issue 11:CD006437, 2017
4- Erikci VS. Pediatric appendicitis and its management: a review article. Clinics in Surgery. 2:1825, 2017
5- Ceresoli M, Tamini N, Gianotti L, Braga M, Nespoli L. Are endoscopic loop ties safe even in complicated acute appendicitis? A systematic review and meta-analysis. International Journal of Surgery. 68:40–47. (Referenced through commentary), 2019
6- Flores-Marín K, Rodríguez-Parra A, Trejo-Ávila M, Cárdenas-Lailson E, Delano-Alonso R, Valenzuela-Salazar C, Herrera-Esquivel J, Moreno-Portillo M. Laparoscopic appendectomy in complicated appendicitis with compromised appendix base: a retrospective cohort study. Cirugía y Cirujanos. 89(5):651–656, 2021
7- Das S, Ghosh A, Chakraborty P, Halder P. Appendicular stump blowout following an emergency appendectomy: an unusual complication. Pediatrics & Health Research. 6(6):25, 2021

PSU Volume 65 No 05 NOVEMBER 2025

Extraosseous Ewing's Sarcoma


Extraosseous Ewing's Sarcoma (EES) represents a distinct clinical and pathological entity within the Ewing Sarcoma Family of Tumors, arising in soft tissues without bone involvement. Though accounting for 20–30% of Ewing sarcoma cases, EES is rare, especially in the pediatric population. Its epidemiology, molecular underpinnings, clinical presentation, and therapeutic responses mirror, yet diverge in critical ways from, osseous Ewing sarcoma.


Pediatric EES exhibits a bimodal age distribution, peaking under five years and again in adolescence. It predominantly affects Caucasians, with a slight male preponderance. The incidence rate is roughly 0.4 per million children per year. Most tumors occur in the deep soft tissues of the trunk, thorax, paravertebral regions, or extremities. Unlike bone Ewing sarcoma, there appears to be no established racial or sex-based predisposition specific to EES, and familial or environmental risk factors remain unidentified.


Histologically, EES is a small round blue cell tumor that shares immunohistochemical and molecular features with osseous Ewing sarcoma, including strong CD99 membrane positivity and a high incidence of EWSR1 translocations. The most common fusion is EWSR1-FLI1 resulting from t(11;22)(q24;q12), present in about 85–90% of cases. Alternate fusions such as EWSR1-ERG or rare variants involving WT1 have also been documented. These genetic signatures are crucial not only for diagnosis but also for differentiating EES from morphologically similar entities such as rhabdomyosarcoma, lymphoma, or desmoplastic small round cell tumor.


Radiologically, EES typically presents as a large, heterogeneous soft tissue mass with aggressive features—irregular margins, necrotic or cystic areas, hemorrhage, and rich vascularity. CT and MRI are complementary; MRI is particularly useful in delineating tumor extent and neurovascular involvement. Unlike osseous Ewing sarcoma, periosteal reaction and cortical bone destruction are typically absent, although adjacent bone displacement or remodeling may be seen in long-standing cases.


Clinically, patients present with a painless, enlarging mass. Pain occurs in approximately one-third of cases, usually when adjacent structures are compressed. Constitutional symptoms are uncommon at presentation. Metastasis, present at diagnosis in up to 25% of cases, most frequently involves the lungs. Less commonly, bone and bone marrow metastases occur, especially in fusion-positive subtypes.


Prognostically, pediatric EES carries a better outlook than its osseous counterpart, with 5-year overall survival rates ranging from 65–85% in localized disease, though outcomes vary significantly by site, tumor volume, and completeness of surgical resection. Prognosis declines sharply in metastatic or unresectable cases. Tumor volume greater than 200 mL is a recognized adverse prognostic factor. The thoracic region and pelvis are common primary sites with comparatively lower survival rates, likely due to challenges in achieving local control and the high propensity for pleural extension.


Treatment is multimodal, combining systemic chemotherapy with local control via surgery, radiation, or both. The standard chemotherapeutic regimen is interval-compressed VDC/IE (vincristine, doxorubicin, cyclophosphamide alternating with ifosfamide and etoposide), typically delivered over 14–17 cycles. This backbone is supported by strong evidence from the Children's Oncology Group (COG) and other cooperative groups. The addition of vincristine-topotecan-cyclophosphamide (VTC) to standard chemotherapy failed to improve survival in randomized trials, reinforcing the efficacy of current regimens.


Surgery plays a more decisive role in EES than in osseous disease. Complete resection with negative margins is a robust positive prognostic factor. Tumors in resectable locations, such as the extremities or superficial trunk, achieve higher local control rates and better outcomes. In contrast, tumors arising in axial or deep pelvic locations often require multimodal local therapy, and when surgery is not feasible, radiotherapy is used either as a definitive or adjunct modality.


The radiosensitivity of EES enables its use for unresectable tumors or where negative margins cannot be achieved. However, long-term toxicity—especially in growing children—remains a concern, and thus radiation is reserved for selected cases. The evolution of conformal radiation and intensity-modulated techniques has allowed better dose delivery while limiting damage to adjacent critical structures.


Molecular profiling is reshaping risk stratification and treatment paradigms. The presence of EWSR1-FLI1 fusion, particularly type 1 fusions, appears to confer a more favorable prognosis than alternative or complex translocations. Fusion-negative cases, though rare, show heterogeneous biology and may behave more like other small round blue cell tumors. The role of targeted therapies remains investigational; IGF-1R inhibitors, PARP inhibitors, and epigenetic modulators have shown promise in early-phase trials but are not yet standard care.


Data on long-term survivorship in pediatric EES is limited but growing. A Dutch population-based analysis found that despite improvements in overall survival since the 1990s, adolescents and young adults continue to experience poorer outcomes compared to younger children. This disparity persists across stages, tumor sites, and tissue of origin. It is likely multifactorial—driven by biological, pharmacological, psychosocial, and healthcare access differences.


Meta-analyses reveal that recurrence rates in pediatric EES range from 25–35%, with secondary metastases in up to 16% of cases. Combined local therapy (surgery plus radiation) appears to offer superior local control compared to monotherapy, particularly for tumors in challenging anatomical locations. Chemotherapy remains indispensable for systemic control, and its omission or delay correlates with worse outcomes.


Importantly, the literature emphasizes the need for centralized care in high-volume centers, where multidisciplinary teams can integrate advanced imaging, pathology, surgery, radiation, and supportive care. The rarity of EES, especially in the pediatric population, necessitates international collaboration to refine protocols, stratify risk, and identify molecular targets for personalized therapy.


In conclusion, extraosseous Ewing sarcoma in children remains a rare but highly aggressive malignancy requiring coordinated multimodal management. Advances in molecular diagnostics, risk-adapted therapies, and supportive care have improved survival, especially for localized disease. However, metastatic, and unresectable tumors remain formidable challenges. Ongoing trials, molecular stratification, and international cooperation will be key to optimizing outcomes and reducing long-term morbidity in this vulnerable population.

References:
1- Gurria JP, Dasgupta R. Rhabdomyosarcoma and Extraosseous Ewing Sarcoma. Children (Basel). 5(12):165, 2018
2- Leavey PJ, Laack NN, Krailo MD, Buxton A, Randall RL, DuBois SG, Reed DR, Grier HE, Hawkins DS, Pawel B, Nadel H, Womer RB, Letson GD, Bernstein M, Brown K, Maciej A, Chuba P, Ahmed AA, Indelicato DJ, Wang D, Marina N, Gorlick R, Janeway KA, Mascarenhas L. Phase III Trial Adding Vincristine-Topotecan-Cyclophosphamide to the Initial Treatment of Patients With Nonmetastatic Ewing Sarcoma: A Children's Oncology Group Report. J Clin Oncol. 2021 Dec 20;39(36):4029-4038. Erratum in: J Clin Oncol. 40(21):2393, 2022
3- Alexander A, Hunter K, Rubin M, Bhat AP. Extraosseous Ewing's Sarcoma: Pictorial Review of Imaging Findings, Differential Diagnosis, and Pathologic Correlation. Indian J Radiol Imaging. 31(1):203-209, 2021
4- Ghandour M, Lehner B, Klotz M, Geisbüsch A, Bollmann J, Renkawitz T, Horsch A. Extraosseous Ewing Sarcoma in Children: A Systematic Review and Meta-Analysis of Clinicodemographic Characteristics. Children (Basel). 9(12):1859, 2022
5- Ioannidou M, Tsotridou E, Samoladas E, Tragiannidis A, Kouskouras K, Sfougaris D, Spyridakis I, Foroulis C, Galli-Tsinopoulou A, Hatzipantelis E. Unusual Manifestation of Extraosseous Ewing Sarcoma: Report of 3 Cases. Balkan J Med Genet. 25(2):77-81, 2023
6- Ghandour M, Semaan K, Saad E, Horsch A, Abdallah R, Semaan D. Clinicodemographic characteristics of extraosseous ewing sarcoma: A comparative meta-analysis of pediatric and adult patients. J Orthop. 44:86-92, 2023
7- Schulpen M, Haveman LM, van der Heijden L, Kaal SEJ, Bramer JAM, Fajardo RD, de Haan JJ, Hiemcke-Jiwa LS, Ter Horst SAJ, Jutte PC, Schreuder HWB, Tromp JM, van der Graaf WTA, van de Sande MAJ, Gelderblom H, Merks JHM, Karim-Kos HE. The survival disparity between children and adolescents and young adults (AYAs) with Ewing sarcoma in the Netherlands did not change since the 1990s despite improved survival: A population-based study. Eur J Cancer. 208:114209, 2024

Hepatic Mesenchymal Hamartoma

Hepatic mesenchymal hamartoma (HMH) is an uncommon but clinically significant benign liver tumor, predominantly affecting children under the age of three. Although histologically benign, its presentation, size, and potential for malignant transformation present unique diagnostic and therapeutic challenges. The condition is the second most common benign hepatic tumor in the pediatric population, following infantile hemangioma. It is believed to arise from disorganized proliferation of primitive mesenchymal tissue within the liver, specifically in the periportal region, leading to a variable composition of stromal, ductal, vascular, and hepatic elements.


Most children with HMH present with nonspecific signs and symptoms. Abdominal distension is the most frequent clinical finding, often noticed by parents or healthcare providers due to a visible or palpable mass. Less commonly, patients may report or present with discomfort, vomiting, or systemic symptoms like fever or fatigue. In neonates, the mass effect can be significant enough to cause respiratory compromise or anemia due to rapid expansion or internal bleeding. Rarely, prenatal presentations have been documented, where fetal imaging reveals an abdominal mass leading to concerns such as polyhydramnios or preterm labor. In a number of prenatal cases, the tumor was mistaken for other liver abnormalities until postnatal evaluation clarified the diagnosis.


Diagnostic evaluation usually begins with imaging. Ultrasonography often shows a cystic or mixed cystic-solid hepatic mass, and its accessibility and safety make it the first-line imaging modality. On ultrasound, HMH may present with thin-walled, multiseptated cysts or heterogeneous areas depending on the tumor's internal composition. Color and power Doppler ultrasound may reveal minimal vascularity, which helps to distinguish it from more aggressive lesions. In computed tomography (CT) and magnetic resonance imaging (MRI), the mass typically appears as a large, well-circumscribed lesion with cystic and solid components. The classic "Swiss cheese" appearance—representing interspersed cystic and solid areas—is often observed on contrast-enhanced CT. Cystic regions usually show low attenuation, while solid portions may enhance heterogeneously. MRI further characterizes the lesion with high signal intensity in cystic areas on T2-weighted images, due to fluid accumulation, and variable signal on T1-weighted images depending on protein content.


The differential diagnosis is broad and includes hepatoblastoma, undifferentiated embryonal sarcoma of the liver (UESL), hemangioma, biliary cystadenoma, and parasitic infections like hydatid cysts. A particularly challenging scenario arises when alpha-fetoprotein (AFP) is mildly elevated, as elevated AFP levels are often associated with malignant liver tumors such as hepatoblastoma. However, mild to moderate AFP elevation has been observed in some cases of HMH, possibly due to regenerative hepatocytes within the lesion or associated inflammation. Hence, AFP levels alone cannot reliably distinguish between benign and malignant hepatic masses in children.


Histologically, HMH is composed of a mixture of myxoid mesenchymal stroma, malformed bile ducts, blood vessels, lymphatic channels, and entrapped hepatocytes. The stromal component is typically loose and edematous, with stellate-shaped mesenchymal cells, while the epithelial elements form ductal structures reminiscent of ductal plate malformations. In some areas, the lesion may display extensive cystic degeneration. The cysts are often not true epithelial-lined structures but rather pseudocysts arising from stromal liquefaction. Immunohistochemistry supports the diagnosis, with vimentin positivity in mesenchymal cells, cytokeratin expression in ductal elements, and occasional positivity for desmin and smooth muscle actin.


Cytogenetic studies have provided insights into the underlying pathogenesis. Several cases of HMH have demonstrated chromosomal abnormalities, most notably translocations involving chromosome 19q13.4. This region includes the C19MC microRNA cluster, which is normally active in placental tissue but has been implicated in abnormal proliferation when dysregulated. Fusion genes involving MALAT1 at 11q13 and C19MC have been identified in both HMH and UESL, supporting the hypothesis that HMH and UESL may lie on a spectrum, with potential for malignant transformation under certain conditions. The presence of such cytogenetic similarities between benign and malignant pediatric liver tumors underscores the importance of thorough histological sampling, especially in recurrent or rapidly growing tumors.


Syndromic associations, although rare, have been reported. Some cases of HMH have been identified in children with Beckwith-Wiedemann Syndrome, a congenital overgrowth disorder associated with increased risk of various embryonal tumors. The connection may be mediated through shared pathways involving paternal uniparental disomy and imprinting defects at 11p15. In other reports, HMH has been found in conjunction with placental mesenchymal dysplasia, further supporting a developmental etiology linked to epigenetic abnormalities. Although earlier reports hypothesized that HMH is solely a developmental anomaly, accumulating molecular data suggest that it may represent a benign neoplasm with limited growth potential in most cases but with malignant potential in select circumstances.


Management of HMH depends on the size, symptoms, and extent of the lesion. Complete surgical resection remains the gold standard treatment and is typically curative. Enucleation or lobectomy is performed based on the tumor's location and involvement of hepatic structures. In some instances, particularly for giant or multicentric tumors, liver transplantation may be considered, though it is rarely necessary. For lesions causing acute mass effect, preoperative percutaneous aspiration of cystic fluid has been used as a temporizing measure to relieve symptoms and facilitate surgical planning. In select prenatal cases, aspiration has also been performed in utero to manage hydrops fetalis and allow continued gestation.


Advanced surgical planning tools have improved outcomes for complex cases. The application of three-dimensional (3D) simulation systems based on CT imaging has allowed for better preoperative visualization of tumor relationships with hepatic vasculature and bile ducts. Such systems facilitate precise anatomical liver resection, improving safety and minimizing blood loss. During surgery, technologies like intraoperative ultrasound and the Cavitron ultrasonic surgical aspirator (CUSA) are often employed to delineate margins and preserve hepatic function.


Postoperative prognosis for resected HMH is excellent, with most children experiencing full recovery and no recurrence. Follow-up imaging is generally recommended in the first few years to monitor for potential recurrence, particularly in cases where resection margins were close or uncertain. In rare cases of incomplete excision, recurrence may occur and should be managed surgically. Isolated reports of malignant transformation to UESL years after incomplete resection of HMH highlight the need for vigilance in long-term follow-up.


The histologic distinction between HMH and early UESL is sometimes blurred, especially when areas of cellular atypia or increased mitotic activity are present. In such cases, deeper sampling and genetic analysis are advisable. While most UESLs appear de novo, several case studies have demonstrated malignant transformation of previously diagnosed HMH, confirmed by shared genetic abnormalities. This reinforces the importance of viewing HMH not as a uniformly benign lesion but as a biologically dynamic entity, especially when diagnosed beyond infancy or in atypical presentations.


Atypical cases continue to broaden our understanding of this rare tumor. For instance, some children over the age of five have been diagnosed with HMH, contradicting the usual age distribution. In one documented case, a five-year-old boy presented with a hepatic mass initially misdiagnosed as Caroli syndrome based on imaging, highlighting the diagnostic complexity and potential for overlap with congenital biliary disorders. In another case involving a preterm infant, the diagnosis of HMH was delayed due to initial suspicion of hemangioma and administration of propranolol therapy. The tumor continued to enlarge, leading to respiratory compromise and anemia, eventually requiring surgical resection with full recovery.


Despite being a benign tumor, HMH poses significant challenges due to its variable presentation, potential for confusion with malignant lesions, and occasional life-threatening mass effects. Its rarity means that many clinicians may only encounter a few cases over their careers, making awareness and understanding critical. Multimodal imaging, combined with histologic confirmation, remains the cornerstone of diagnosis. Innovations in imaging and surgical planning have improved safety and outcomes, while genetic research continues to uncover the underlying biology and connections with more aggressive pathologies.


In sum, hepatic mesenchymal hamartoma in children is a rare but important pediatric liver tumor, marked by diverse clinical and radiological manifestations. While most cases have an excellent prognosis with appropriate surgical management, the tumor's overlap with malignant entities and occasional genetic instability demands careful evaluation. Continued research into its molecular underpinnings and long-term outcomes will further clarify its nature and guide management strategies.

References:
1- Yen JB, Kong MS, Lin JN. Hepatic mesenchymal hamartoma. J Paediatr Child Health. 39(8):632–634, 2003
2. Kim SH, Kim WS, Cheon JE, Yoon HK, Kang GH, Kim IO, Yeon KM. Radiological spectrum of hepatic mesenchymal hamartoma in children. Korean J Radiol. 8(6):498–505, 2007
3. Zhao J, Zhou XJ, Zhu CZ, Wu Y, Wei B, Zhang G, Hao XW, Zhang H, Jiang Z, Dong Q. 3D simulation assisted resection of giant hepatic mesenchymal hamartoma in children. Comput Assist Surg (Abingdon). 22(1):54–59, 2017
4. Khan MR, Binkovitz LA, Smyrk TC, Potter DD Jr, Furuya KN. Mesenchymal Hamartoma in Children: A Diagnostic Challenge. Case Rep Pediatr. 2019:4132842, 2019
5. Martins-Filho SN, Putra J. Hepatic mesenchymal hamartoma and undifferentiated embryonal sarcoma of the liver: a pathologic review. Hepat Oncol. 7(2):HEP19, 2020
6. Wang Z, Mo J, Lv Z, Gong X, Hong W, Sheng Q. Giant hepatic mesenchymal hamartoma in a preterm newborn: a case report and literature review. Am J Transl Res. 14(12):8782–8787, 2022
7. Venkataraman S, Ur Rahman N, Sharma J, Bhagat A, Valsan A. Hepatic Mesenchymal Hamartoma With Elevated Alpha-Fetoprotein: A Diagnostic Dilemma. Cureus. 16(11):e74791, 2024

Congenital H-Type Tracheoesophageal Fistula

Congenital H-type tracheoesophageal fistula (H-TEF) is a rare developmental anomaly accounting for approximately 4–5% of all congenital tracheoesophageal malformations. Unlike the more common types associated with esophageal atresia, H-TEF presents without interruption of the esophageal lumen, making the diagnosis both elusive and often delayed. Despite its rarity, the condition has serious implications for respiratory health, especially in infants and young children, and demands careful diagnostic strategy and surgical precision.


The clinical presentation of H-TEF is subtle yet persistent. Infants typically exhibit nonspecific symptoms such as choking during feeds, recurrent pneumonia, cyanosis, and respiratory distress. Older children may present with chronic cough or recurrent upper respiratory tract infections that are often misattributed to asthma or gastroesophageal reflux. In numerous cases, these symptoms result in prolonged diagnostic delays, with diagnosis occurring months to years after symptom onset. Some cases are not identified until adolescence or adulthood, underscoring the need for heightened clinical suspicion in any pediatric patient with recurrent respiratory illness and feeding difficulties.


Diagnostic approaches vary, but no single test guarantees early identification. Contrast esophagography remains a cornerstone technique but is frequently insufficient on its own. False negatives are not uncommon due to the small size or valvular nature of the fistulous tract. Repeating the study may be necessary, as demonstrated in multicenter reviews where two or even three studies were often needed to confirm the diagnosis. Bronchoscopy has emerged as the most definitive tool, offering direct visualization and the possibility of fistula cannulation, which aids surgical planning. When combined with fluoroscopy or contrast instillation, bronchoscopy can precisely locate the fistula and reveal coexisting anomalies such as tracheomalacia.


The majority of H-TEFs are located in the cervical region, often above the level of T2. Consequently, the preferred surgical approach is via a right cervical incision, which provides direct access with minimal morbidity. This technique allows for fistula division and primary repair, often with muscle interposition to reduce recurrence risk. In cases where the fistula lies lower in the thoracic cavity or is obscured by anatomical variations, a thoracic approach via thoracotomy or thoracoscopy is used. Thoracoscopic techniques are gaining favor due to their minimally invasive nature and favorable postoperative recovery profiles. In a sizable series, thoracoscopic repair yielded no conversions to open surgery, low complication rates, and rapid discharge times.


Despite surgical advances, complications remain a concern. Vocal cord paralysis is the most commonly reported, with some series citing an incidence as high as 18.5%. This is often due to injury to the recurrent laryngeal nerve during dissection. In most cases, vocal cord function recovers over time, though in some, the damage is permanent and may necessitate secondary intervention. Other complications include fistula recurrence, reported in up to 8% of cases, as well as postoperative gastroesophageal reflux and, rarely, chylothorax. In delayed diagnoses, chronic inflammation and fibrosis around the fistula tract complicate surgical dissection and increase complication risk. In these instances, adjunctive measures like the application of hemostatic patches (e.g., TachoSil®) have been employed to reinforce suture lines and reduce leakage and recurrence.


The choice of surgical technique can significantly impact outcome. The cervical approach, though widely used, carries a higher risk of nerve injury compared to the thoracic route. Thoracoscopy, while technically demanding, offers better visualization and reduces tissue trauma. When performed by experienced surgeons, it has become a strong alternative to traditional open methods. Comparative reviews have highlighted the benefits of bronchoscopy-guided cannulation, which not only assists in localizing the fistula but also improves surgical precision and minimizes operative time.


Long-term outcomes are generally favorable when diagnosis and intervention are timely. Most patients experience complete resolution of symptoms following surgery. However, in the subset with delayed diagnosis, residual issues such as chronic lung disease or feeding difficulties may persist. Follow-up protocols should include vocal cord assessment, pulmonary function monitoring, and surveillance for recurrence. Standardizing these protocols could mitigate late morbidity and improve quality of life for these patients.


In conclusion, congenital H-type tracheoesophageal fistula poses significant diagnostic and therapeutic challenges. Its rarity, subtle presentation, and frequent diagnostic delays demand high clinical vigilance. Esophagography and bronchoscopy remain critical tools in confirming the diagnosis, with bronchoscopy proving most accurate. Surgical repair, ideally via a cervical or thoracoscopic approach, offers excellent outcomes when executed carefully. Future research should focus on refining surgical techniques, minimizing complications such as nerve injury, using neuromonitoring during closure, and exploring the role of adjunctive materials in high-risk or chronically inflamed cases. Early recognition and a structured, multidisciplinary management pathway remain key to improving prognosis in this complex but curable anomaly.

References:
1- Al-Salem AH, Mohaidly MA, Al-Buainain HM, Al-Jadaan S, Raboei E: Congenital H-type tracheoesophageal fistula: a national multicenter study. Pediatr Surg Int. 32(5):487-91, 2016
2- Edelman B, Selvaraj BJ, Joshi M, Patil U, Yarmush J: Anesthesia Practice: Review of Perioperative Management of H-Type Tracheoesophageal Fistula. Anesthesiol Res Pract. 2019:8621801, 2019
3- Sampat K, Losty PD: Diagnostic and management strategies for congenital H-type tracheoesophageal fistula: a systematic review. Pediatr Surg Int. 37(5):539-547, 2021
4- Tiwari C, Nagdeve N, Saoji R, Nama N, Khan MA: Congenital H-type tracheo-oesophageal fistula: An institutional review of a 10-year period. J Mother Child. 24(4):2-8, 2021
5- Toczewski K, Rygl M, Dzielendziak A, Frybova B, Patkowski D: Thoracoscopic repair of congenital isolated H-type tracheoesophageal fistula. J Pediatr Surg. 56(8):1386-1388, 2021
6- Anadolulu AI, Gerçel G, Gördü B, Arslan UE, Boybeyi Ö, Soyer T, Durakbasa ÇU: Comparison of Diagnostic Methods, Surgical Approaches and Outcome for Congenital H-Type Tracheoesophageal Fistula: A Systematic Review. J Pediatr Surg. 60(8):162343, 2025
7- Pierucci UM, Paraboschi I, Zamana C, Canonica CPM, Guazco GIC, Bulfamante AM, Izzo F, Zirpoli S, Camporesi A, Pelizzo G: Delayed diagnosis of isolated congenital H-type tracheoesophageal fistula: a case report of surgical repair supported by TachoSil® as an adjunct in chronically inflamed tissues. Transl Pediatr. 14(7):1668-1674, 2025

PSU Volume 65 No 06 DECEMBER 2025

Liver Transplant for Mesenchymal Hamartoma

Mesenchymal hamartoma of the liver (MHL) is a rare, benign tumor that primarily affects infants and young children, though it has been increasingly documented in adults. Surgical resection remains the treatment of choice; however, when tumors are deemed unresectable—due to size, anatomical constraints, recurrence, or risk of malignant transformation—liver transplantation (LT) becomes a necessary, life-saving alternative. Drawing from several clinical cases and institutional experiences, liver transplantation for MHL, though uncommon, has proven to be both feasible and curative in selected patients.


MHL typically presents in children under two years of age, manifesting as large, cystic hepatic masses. These lesions may cause abdominal distension, respiratory compromise, and gastrointestinal symptoms due to mass effect. Although benign, their presentation can closely mimic malignant liver tumors, particularly hepatoblastoma. In many cases, elevated serum alpha-fetoprotein (AFP) levels help distinguish hepatoblastoma from MHL, as AFP is often significantly elevated in malignancy and only mildly elevated or normal in MHL. Unfortunately, in practice, AFP testing is not always performed preoperatively, leading to diagnostic ambiguity.


One such diagnostic challenge was illustrated in a pediatric case where a 13-month-old boy was initially diagnosed with hepatoblastoma based on imaging and biopsy. Planned chemotherapy was delayed, and surgical resection was carried out instead. Postoperative histology confirmed mesenchymal hamartoma. This case highlighted the critical diagnostic role of serum AFP, which, if measured, might have led to an accurate preoperative diagnosis and avoided unnecessary oncologic interventions.


While resection is curative for most patients with MHL, certain presentations defy surgical removal. In these situations, LT becomes the definitive treatment. A pivotal pediatric case involved a child with Beckwith–Wiedemann Syndrome (BWS), a genetic overgrowth disorder associated with tumor development. The child developed six large mesenchymal hamartomas dispersed throughout the liver, causing significant abdominal mass effect. Resection was not possible due to the number and distribution of lesions. The child underwent successful cadaveric liver transplantation at 25 months of age. At 16-month follow-up, the patient showed no signs of tumor recurrence or graft rejection, marking a successful long-term outcome.


Another institutional review of pediatric liver transplantations included ten children transplanted for primary hepatic tumors, one of whom had MHL. In this case, the patient initially underwent attempted resection. However, the lesion's rapid growth and anatomical complexity necessitated liver transplantation. Although the patient required re-transplantation due to hepatic artery thrombosis four days postoperatively, they ultimately recovered fully. At follow-up, all patients, including the one with MHL, were alive with no evidence of tumor recurrence.


Adult cases of MHL are exceedingly rare but clinically significant due to their potential for massive growth and misdiagnosis. One notable case involved a 34-year-old woman who presented with a 21 kg liver mass that occupied nearly the entire abdominal cavity. Imaging revealed diffuse cystic disease of the liver, displacing other abdominal organs. Standard resection was impossible due to the sheer size and extent of the mass. Orthotopic liver transplantation was performed using a graft from a cardiac-death donor. The postoperative course was uneventful, and one year later, the patient remained healthy and tumor-free.


Another adult patient, aged 46, had previously undergone a right hepatectomy for a large MHL. Despite histologically confirmed clear margins, she presented 2.5 years later with recurrent disease. Imaging suggested extensive recurrence with possible malignant transformation. The lesions were deemed unresectable, and the patient underwent orthotopic liver transplantation. Pathological examination confirmed recurrent but benign MHL. Six months post-transplant, the patient showed no signs of disease or complications. This case is reportedly the first in the English literature to document liver transplantation for recurrent MHL.


A younger adult patient, 26 years old, was admitted with a massive hepatic mass occupying the right lobe. Imaging and biopsy suggested MHL, and surgical planning ruled out the need for transplantation due to a sufficient future liver remnant. A successful right hemi-hepatectomy was performed. The excised tumor weighed 8 kg and measured 35 cm. Histology confirmed MHL, and the patient was followed for 42 months with no signs of recurrence. However, the case reinforced the concern that giant MHLs carry a risk for recurrence and potential transformation, prompting discussion about the possible role of LT in similarly borderline cases.


The histological hallmark of MHL includes loose myxoid stroma, spindle cells, bile ducts, and islands of immature hepatocytes. Immunohistochemistry typically reveals positivity for desmin and smooth muscle actin in the stromal component, and cytokeratin 7 in the bile duct elements. In some cases, cytogenetic analysis has detected chromosomal abnormalities, such as loss of 19q13, raising concerns about malignant potential and supporting the rationale for aggressive surgical or transplant-based treatment in selected patients.


Surgical techniques for transplantation in these patients generally follow standard orthotopic liver transplant protocols. Some institutions favor the piggyback technique, especially in pediatric cases where anatomical variation and vessel size pose technical challenges. Immunosuppression typically involves tacrolimus-based therapy, often initiated with corticosteroids, and followed by maintenance with mycophenolate mofetil or mTOR inhibitors. The latter are sometimes chosen in cases with oncologic concerns due to their antiproliferative properties.


Outcomes across the reviewed cases were uniformly positive. All transplanted patients survived the perioperative period and showed no recurrence at follow-up ranging from six months to three years. The primary complications included hepatic artery thrombosis and biliary strictures, both manageable with current surgical and interventional approaches. Importantly, none of the transplanted MHL cases demonstrated histologic evidence of malignant transformation, although the risk remains theoretical and justifies the aggressive treatment approach.


Taken together, these cases illustrate a consistent narrative: MHL, while benign, can behave in clinically aggressive ways. Massive growth, risk of rupture, recurrence, and the small but real potential for malignant transformation make management challenging, particularly when tumors are unresectable. Liver transplantation has proven to be a definitive solution in these rare but high-stakes scenarios. The decision to proceed with LT should be made in high-volume centers with experience in hepatobiliary surgery and transplantation, ideally supported by multidisciplinary tumor boards.


Moreover, these cases point to a diagnostic gap: the frequent initial misclassification of MHL as malignant disease. This has significant implications for treatment planning and highlights the need for a cautious, comprehensive diagnostic approach that includes serum AFP, advanced imaging, and, where possible, confirmatory histology with immunohistochemical profiling.


The role of surveillance post-resection also emerges as a key issue. While historically considered unnecessary for benign tumors, the recurrence of MHL in a resected adult patient suggests that regular follow-up imaging may be prudent, especially when resection margins are narrow or when tumors exhibit atypical features.


In conclusion, liver transplantation offers a safe and effective treatment for mesenchymal hamartoma of the liver when surgical resection is not feasible. The excellent survival and absence of recurrence across reported cases underscore its role as a curative option. As diagnostic tools improve and long-term data accumulate, LT may become more widely accepted for MHL in select pediatric and adult patients, particularly those with complex, recurrent, or high-risk presentations.

References:
1- Tannuri AC, Tannuri U, Gibelli NE, Romão RL. Surgical treatment of hepatic tumors in children: lessons learned from liver transplantation. J Pediatr Surg. 2009 Nov;44(11):2083-7.
2- Bahador A, Geramizadeh B, Rezazadehkermani M, Moslemi S. Mesenchymal hamartoma mimicking hepatoblastoma. Int J Organ Transplant Med. 2014;5(2):78-80.
3- Li J, Cai JZ, Guo QJ, Li JJ, Sun XY, Hu ZD, Cooper DK, Shen ZY. Liver transplantation for a giant mesenchymal hamartoma of the liver in an adult: Case report and review of the literature. World J Gastroenterol. 2015 May 28;21(20):6409-16.
4- Pan ET, Yoeli D, Kueht ML, Galvan NTN, Cotton RT, O'Mahony CA, Rana A, Goss JA. Liver transplantation as definitive treatment of an unresectable mesenchymal hamartoma in a child with Beckwith-Wiedemann Syndrome. J Surg Case Rep. 2017 Aug 31;2017(8):rjx167.
5- Idrees M, Chung K, Philipoff A, Jeffrey G, Garas G, Jaques B, Delriviere L, De Boer B, Bhandari M, Mou L. Liver Transplant for Adult Recurrent Hepatic Mesenchymal Hamartoma and a Feasible Treatment Modality: A Case Report and Literature Review. Transplant Proc. 2022 Jul-Aug;54(6):1636-1639.
6- Pinelli D, Guerci C, Cammarata F, Cirelli R, Scatigno A, Colledan M. Huge mesenchymal hamartoma in a young adult: a case report. J Surg Case Rep. 2024 Apr 1;2024(4):rjae184.
7- Selzer Soria EM, González Campaña A, Siaba Serrate A, Varela M, Lagues C, Fauda M, Malla I. Liver transplantation for primary liver tumors in pediatrics. A case series. Arch Argent Pediatr. 2025 Feb 1;123(1):e202310222.

Pediatric Interfacility Transfer in Suspected Appendicitis

Pediatric interfacility transfers are increasingly common in the United States, driven by the centralization of specialized pediatric services and the growing reliance on tertiary care hospitals for advanced diagnostic and surgical interventions. Among the many clinical indications prompting such transfers, suspected appendicitis represents a condition that illustrates both the potential benefit and the unintended consequences of regionalization.


Over the past two decades, research has documented a significant shift in where and how children with acute surgical conditions—including appendicitis—receive care. Analysis of state and national databases has revealed that more than 30% of pediatric transfers for abdominal pain or suspected appendicitis result in no surgical or imaging intervention at the receiving hospital. These "non-intervention" cases often indicate that the transfer may have been avoidable, raising serious concerns about resource use, patient safety, and healthcare equity.


At the same time, advances in diagnostic criteria, improved access to telehealth consultations, and the refinement of hospital capabilities metrics—such as the Pediatric Hospital Capability Index—offer opportunities to reduce unnecessary transfers while maintaining high-quality care.

Appendicitis remains one of the most common surgical emergencies in children. However, its presentation can be subtle or atypical, particularly in younger children. Typical symptoms—fever, migratory right lower quadrant pain, anorexia, and vomiting—are not always present, especially in early stages or among preschool-aged patients. Diagnostic uncertainty at community hospitals often prompts transfer, particularly when pediatric imaging, surgical consults, or pediatric-trained emergency physicians are not available.


However, not all transfers are necessary. A 2024 study from Children's Hospital Los Angeles found that nearly 29% of transfers for suspected appendicitis did not result in appendectomy, suggesting the initial diagnosis was either incorrect or managed non-operatively. These patients were often younger, presented with milder symptoms, and had lower inflammatory markers such as WBC count, CRP, and neutrophil percentage.


Avoidable transfers have distinct characteristics:

• Younger age (median 9 vs. 11 years)

• Shorter duration of symptoms

• Atypical symptom presentation

• Lower serum inflammatory markers

• Normal or indeterminate imaging

• High likelihood of repeat imaging at the receiving center


In contrast, appropriate transfers more often result in appendectomy and tend to show clear clinical and laboratory evidence of acute appendicitis. Transfers for such cases are both medically justified and outcome-improving.


These findings reinforce the critical role of initial diagnostic accuracy and clinical judgment in deciding when to transfer.


Do's and Don'ts in Pediatric Interfacility Transfer for Suspected Appendicitis


DO:

• Use structured communication protocols. Verbal handoffs should follow a standardized format. The I-PASS tool, while primarily used in intra-hospital settings, has shown promise in improving interfacility handoffs by including critical elements such as illness severity, action lists, and contingency plans.

• Provide complete and clear documentation. Referral notes should include symptom chronology, physical exam findings, imaging results (preferably with digital copies), lab values, and reasoning for suspected diagnosis.

• Consult pediatric surgical specialists remotely before initiating a transfer, especially for borderline or atypical presentations. Telehealth consultations can prevent unnecessary patient movement.

• Assess pediatric readiness of the referring facility. Facilities with higher pediatric readiness scores are statistically less likely to transfer non-injured children unnecessarily. Boosting local readiness (e.g., staff training, pediatric coordinators, access to ultrasound) could mitigate the need for transfer.

• Evaluate socioeconomic and geographic impact. Understand that transfers often mean lost workdays, long travel, and financial hardship for families—especially those from rural communities.


DON'T:

• Don't transfer solely due to lack of immediate imaging. Many cases can be triaged with observation, serial exams, and tele-radiology input.

• Don't rely on ultrasound alone without context. A non-diagnostic ultrasound, especially when labs and clinical findings are normal, does not justify urgent transfer in most cases.

• Don't skip communication between transferring and receiving physicians. Referring clinicians often fail to explicitly discuss illness severity or working diagnosis, while receiving physicians rarely summarize information back, increasing the risk of miscommunication.

• Don't treat all abdominal pain as surgical until proven otherwise. This defensive posture can lead to over-transfer, especially in hospitals with no surgical services. Risk stratification should be nuanced, not reactive.


Inadequate pediatric resources at community hospitals—such as absence of on-call pediatric surgeons or low-volume emergency departments—drive much of the transfer volume. Facilities with low pediatric patient volumes are significantly less likely to have written transfer guidelines or agreements, increasing variability and risk in decision-making.


Implementation of formal interfacility transfer agreements and pediatric-specific protocols improves safety and standardizes expectations. National data shows that hospitals with pediatric emergency care coordinators and defined transfer policies perform better on safety and quality metrics.


Further, providers at non-specialty centers often report lacking confidence or training in pediatric surgical triage. In one national survey, the majority of referring providers were general emergency physicians without pediatric specialization, frequently citing the lack of inpatient beds or surgical backup as the main reason for transfer—even when clinical severity did not require it.


While interfacility transfer remains a critical part of pediatric emergency care, especially for surgical emergencies like appendicitis, it must be guided by clinical criteria, diagnostic clarity, and communication excellence. Avoidable transfers impose unnecessary burdens on families and the healthcare system. By applying evidence-based decision-making, fostering teleconsultative support, and strengthening pediatric readiness in community settings, we can reduce unnecessary transfers without compromising care.


The data strongly suggest that a collaborative, stratified approach to suspected pediatric appendicitis—rather than a reflexive transfer policy—can lead to better outcomes, lower costs, and improved patient satisfaction. Standardized communication, thoughtful risk assessment, and investment in local pediatric capability are the cornerstones of this transformation.


Given the complex clinical and legal implications of accepting transferred pediatric patients—especially in cases of suspected appendicitis—it is essential that receiving institutions ensure appropriate medical liability coverage for their on-call surgical staff. Surgeons who assume care of transferred patients inherit full responsibility for diagnosis, treatment decisions, and outcomes, often without access to complete prior records or standardized communication from the referring site. Without institutional malpractice coverage, this creates an unfair exposure to legal risk and may discourage providers from accepting transfers. To safeguard patient access to timely care, reduce institutional liability, and support clinical decision-making in high-risk scenarios, hospitals must offer institutional medico-legal protection for surgeons receiving pediatric transfers.

References:
1- Fendya DG, Genovesi A, Belli K, Page K, Vernon DD. Organized interfacility transfer processes: an opportunity to improve pediatric emergency care. Pediatr Emerg Care. 2011 Oct;27(10):900-906.
2- França UL, McManus ML. Outcomes of Hospital Transfers for Pediatric Abdominal Pain and Appendicitis. JAMA Netw Open. 2018 Oct 5;1(6):e183249.
3- Genovesi AL, Olson LM, Telford R, Fendya D, Schenk E, Morrison-Quinata T, Edgerton EA. Transitions of Care: The Presence of Written Interfacility Transfer Guidelines and Agreements for Pediatric Patients. Pediatr Emerg Care. 2019 Dec;35(12):840-845.
4- Li J, Pryor S, Choi B, Rees CA, Senthil MV, Tsarouhas N, Myers SR, Monuteaux MC, Bachur RG. Profile of Interfacility Emergency Department Transfers: Transferring Medical Providers and Reasons for Transfer. Pediatr Emerg Care. 2019 Jan;35(1):38-44.
5- Lieng MK, Marcin JP, Sigal IS, Haynes SC, Dayal P, Tancredi DJ, Gausche-Hill M, Mouzoon JL, Romano PS, Rosenthal JL. Association between emergency department pediatric readiness and transfer of noninjured children in small rural hospitals. J Rural Health. 2022 Jan;38(1):293-302.
6- Thirnbeck CK, Espinoza ET, Beaman EA, Rozen AL, Dukes KC, Singh H, Herwaldt LA, Landrigan CP, Reisinger HS, Cifra CL. Interfacility Referral Communication for PICU Transfer. Pediatr Crit Care Med. 2024 Jun 1;25(6):499-511.
7- O'Guinn ML, Keane OA, Lee WG, Feliciano K, Spurrier R, Gayer CP. Clinical Characteristics of Avoidable Patient Transfers for Suspected Pediatric Appendicitis. J Surg Res. 2024 Aug;300:54-62.
8- Van Arendonk KJ, Tracy ET, Ellison JS, Flynn-O'Brien KT, Gadepalli SK, Goldin AB, Hall M, Leraas HJ, Ricca RL, Ehrlich PF. Interfacility Transfer of Children With Time-Sensitive Surgical Conditions, 2002-2017. JAMA Netw Open. 2024 Oct 1;7(10):e2440251.

Vaping in Adolescents

Vaping among adolescents has evolved into a significant global public health concern, driven by rapid technological innovation, aggressive marketing, and widespread misconceptions about its safety. Initially introduced as a smoking cessation aid for adult smokers, vaping products—also known as electronic nicotine delivery systems (ENDS)—have instead found a substantial and growing user base among youth. The implications of this trend are far-reaching, spanning neurodevelopmental harm, respiratory diseases, addiction, and broader behavioral and societal impacts.


At the core of vaping's appeal to adolescents is its slick, modern design, and availability in an array of enticing flavors, from fruit and candy to mint and dessert profiles. These devices are often sleek, concealable, and even resemble everyday items like USB drives, making them easy to hide from adults. The perception that vaping is less harmful than traditional cigarettes has further fueled its popularity among teenagers, despite mounting evidence to the contrary.


Nicotine exposure during adolescence has been consistently associated with adverse effects on the developing brain. The adolescent brain undergoes significant growth and reorganization, particularly in areas related to attention, decision-making, and emotional regulation. Nicotine disrupts this maturation process, leading to long-term cognitive and behavioral impairments. Youth who vape are more likely to experience attention deficits, mood disorders, and reduced academic performance. Moreover, early nicotine exposure increases susceptibility to future addiction—not only to nicotine but to other substances, including alcohol, cannabis, and stimulants.


The addictive potential of vaping devices is intensified by the high concentrations of nicotine in many e-liquids, especially those using nicotine salts. Some pods contain as much nicotine as an entire pack of cigarettes, and adolescents may unknowingly consume large amounts in a short period due to the absence of harsh smoke and the smoothness of inhalation. The result is rapid onset of dependency, marked by strong cravings, withdrawal symptoms, and tolerance, even among those who previously had no history of tobacco use.


Health risks extend beyond neurodevelopment. The aerosol inhaled through vaping is not just "harmless water vapor" as often advertised; it contains a cocktail of chemicals, including propylene glycol, glycerin, flavoring agents, and heavy metals like nickel and lead. These substances can cause significant damage to lung tissue, leading to chronic respiratory conditions such as bronchitis, asthma exacerbations, and decreased lung function. Acute lung injuries linked to vaping—collectively referred to as EVALI (e-cigarette or vaping-associated lung injury)—have been reported in thousands of cases, some requiring hospitalization and mechanical ventilation.


The pathophysiology of EVALI is complex. It often involves a severe inflammatory response within the lungs, leading to conditions such as acute eosinophilic pneumonia or organizing pneumonia. While the exact agents responsible are still under investigation, vitamin E acetate has been implicated in many THC-containing products. However, nicotine-only products have also been associated with lung injuries, underscoring the risk inherent in a wide range of vaping substances.


Secondhand exposure presents additional concern. Aerosols released into the air by vapers contain ultrafine particles, volatile organic compounds, and nicotine, all of which can be inhaled by bystanders. This passive exposure is especially troubling in indoor environments such as homes, cars, or schools, where children and non-smoking peers may be involuntarily affected.


Social and behavioral factors contribute to the proliferation of vaping among adolescents. Peer influence, social media exposure, and celebrity endorsements glamorize vaping and normalize its use. Adolescents report vaping out of curiosity, for the "buzz," or as a social activity. Alarmingly, many youth who initiate vaping have never smoked a traditional cigarette, indicating that vaping is not replacing smoking in this population—it is creating a new cohort of nicotine users.


Longitudinal data reveal that adolescents who vape are significantly more likely to transition to traditional cigarettes and cannabis products later in life. This gateway effect challenges the narrative that vaping is a harm reduction tool. Instead, it functions as an on-ramp to broader substance use and risky behaviors. The dual use of vaping and smoking is particularly concerning, as it exposes individuals to compounded health risks.


The cardiopulmonary implications of vaping are also under increasing scrutiny. Nicotine elevates heart rate and blood pressure by stimulating the sympathetic nervous system, and chronic exposure can lead to vascular remodeling and increased risk of heart disease. Other aerosol constituents, such as diacetyl and 2,3-pentanedione, are linked to bronchiolitis obliterans ("popcorn lung"), a debilitating and irreversible lung condition. Moreover, flavoring chemicals and solvents used in e-liquids can generate reactive aldehydes during heating, contributing to oxidative stress, endothelial dysfunction, and tissue damage.


Despite these risks, regulation has often lagged behind the market. In many countries, laws aimed at restricting youth access to vaping products have only recently been introduced or are inconsistently enforced. Flavored e-liquids remain widely available, and marketing strategies continue to target youth, directly or indirectly. Regulatory loopholes allow manufacturers to introduce new formulations or devices that evade existing restrictions.


Public health organizations globally have taken varying stances. While some, such as Public Health England, have promoted vaping as a harm reduction strategy for adult smokers, others—like the World Health Organization and numerous pediatric associations—have emphasized the potential for harm among youth and have called for tighter restrictions. The tension between supporting adult cessation and preventing youth uptake is a major challenge for policy-making.


Effective interventions must target multiple levels. Educational campaigns that debunk myths about vaping safety and highlight its risks are critical. Clinicians should be proactive in screening adolescents for vaping behaviors and providing support for cessation. School-based programs and peer-led initiatives can foster environments that discourage use. Parental involvement is also essential; many parents remain unaware of the signs of vaping or the risks it poses.


Moreover, there is a need for the development of youth-focused cessation tools. Most current cessation programs are designed for adults and may not resonate with adolescents. Mobile apps, counseling, and behavioral therapies tailored to younger users show promise, but require further investment and research.


In conclusion, vaping among adolescents is a complex and escalating public health issue. While initially presented as a less harmful alternative for adult smokers, its widespread use among youth has introduced new avenues for addiction and disease. The risks to brain development, respiratory health, and behavioral outcomes are well-documented and growing. To address this crisis, a coordinated response involving policy, education, clinical practice, and community engagement is essential. Failure to act decisively risks normalizing nicotine use for a new generation and reversing decades of progress in tobacco control.

References:
1- Bhatt JM, Ramphul M, Bush A. An update on controversies in e-cigarettes. Paediatr Respir Rev. 36:75-86, 2020
2- Bhave SY, Chadi N. E-cigarettes and Vaping: A Global Risk for Adolescents. Indian Pediatr. 58(4):315-319, 2021
3- Bravo-Gutiérrez OA, Falfán-Valencia R, Ramírez-Venegas A, Sansores RH, Ponciano-Rodríguez G, Pérez-Rubio G. Lung Damage Caused by Heated Tobacco Products and Electronic Nicotine Delivery Systems: A Systematic Review. Int J Environ Res Public Health. 18(8):4079, 2021
4- Lyzwinski LN, Naslund JA, Miller CJ, Eisenberg MJ. Global youth vaping and respiratory health: epidemiology, interventions, and policies. NPJ Prim Care Respir Med. 32(1):14, 2022
5- Rose JJ, Krishnan-Sarin S, Exil VJ, Hamburg NM, Fetterman JL, Ichinose F, Perez-Pinzon MA, Rezk-Hanna M, Williamson E; American Heart Association Councils. Cardiopulmonary Impact of Electronic Cigarettes and Vaping Products: A Scientific Statement From the American Heart Association. Circulation. 148(8):703-728, 2023
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