Multidisciplinary approach to patients with lymphatic conduction disorders.

Patients with lymphatic disorders are remarkably complex and require a wide variety of medical and surgical services. Establishing a multidisciplinary program improves the efficiency of the patients' hospital experience minimizing the compartmentalization of their care. Offering a clear intake process guarantees that patients will be seen promptly by all the required teams. Additionally, having regular multidisciplinary meetings allows all participating teams to learn from each other and gain experience in the care of a population that is extraordinarily heterogeneous. Additionally, establishing a solid program allows for long-term data collection, research and education.

Surgical management of thoracic duct anomalies.

The development of new imaging techniques for the study of the central lymphatic system allows us to understand the anatomy and pathophysiology of all the disorders of the thoracic duct. With the help of catheters placed percutaneously in the thoracic duct, we can do now complex operations on the thoracic duct to restore its functionality. Advance imaging, expert percutaneous skills, and expert microsurgical skills are critical to the success of these interventions.

Surgical management of chronic lymphatic pleural effusions and chronic lymphatic ascites.

Patients with central lymphatic conduction disorders commonly have recalcitrant pleural effusions and or ascites. These conditions cause a profound deterioration in the patient's quality of life. Support measures such as low-fat diet and diuretics alone hardly ever provide meaningful improvement. New understanding of the pathophysiology of these disorders has opened the door in recent years to the development of several surgical procedures that have remarkable success rates. However, these patients must be managed by expert multidisciplinary teams.

Surgical Management of Central Lymphatic Conduction Disorders: A Review.

AIM: Recent advances in lymphatic imaging allow understanding the pathophysiology of lymphatic central conduction disorders with great accuracy. This new imaging data is leading to a wide range of novel surgical interventions. We present here the state-of-the-art imaging technology and current spectrum of surgical procedures available for patients with these conditions. METHOD: Descriptive report of the newest lymphatic imaging technology and surgical procedures and retrospective review of outcome data. RESULTS: There are currently two high-resolution imaging modalities for the central lymphatic system: multi-access dynamic contrast-enhanced MR lymphangiogram (DCMRL) and central lymphangiography (CL). DCMRL is done by accessing percutaneously inguinal and mesenteric lymph nodes and periportal lymphatics vessels. DCMRL provides accurate anatomical and dynamic data on the progression, or lack thereof, of the lymphatic fluid throughout the central lymphatic system. CL is done by placing a catheter percutaneously in the thoracic duct (TD). Pleural effusions are managed by pleurectomy and intraoperative lymphatic glue embolization guided by CL. Anomalies of the TD are managed by TD-to-vein anastomosis and/or ligation of aberrant TD branches. Chylous ascites and organ-specific chylous leaks are managed by intraoperative glue embolization, surgical lymphocutaneous fistulas, and ligation of aberrant peripheral lymphatic channels, among several other procedures. CONCLUSION: The surgical management of lymphatic conduction disorders is a new growing field within pediatric general surgery. Pediatric surgeons should be familiar with the newest imaging modalities of the lymphatic system and with the surgical options available for patients with these complex surgical conditions to provide prompt treatment or referral. LEVEL OF EVIDENCE: V.

Surgical creation of lymphocutaneous fistulas for the management of infants with central lymphatic obstruction.

PURPOSE: Central lymphatic obstructions are associated with anasarca and high mortality. We hypothesized that opening dilated cutaneous lymphatic channels by creating a lymphocutaneous fistula (LCF) would decompress the lymphatic circulation and improve anasarca. METHODS: We reviewed all patients that had at least one LCF created between 9/2019 and 12/2022. LCF efficacy was determined by changes in weight, urine/diuresis, ventilation, and clinical status. RESULTS: We created eleven LCFs in four infants. LCFs initially drained 108 cc/kg/d (IQR68-265 cc/kg/d). Weights significantly decreased after LCF creation (6.9 [IQR6.1-8.1] kg vs. 6.1 [IQR 4.9-7.6] kg, P = 0.042). Ventilatory support decreased significantly in all patients after at least one LCF was created, and 3/4 patients (75%) had significantly lower peak inspiratory pressures (28 [IQR 25-31] cmH2O vs. 22 [IQR 22-24] cmH2O, P = 0.005; 36 [IQR36-38] cmH2O vs. 33 [IQR 33-35] cmH2O, P = 0.002; 36 [IQR 34-47] cmH2O vs. 28 [28-31] cmH2O, P = 0.002). LCFs remained patent for 29d (IQR 16-49d). LCFs contracted over time, and 6/11 (54.5%) were eventually revised. There were no complications. Two patients died from overwhelming disease, one died from unrelated causes, and one remains alive 29 months after their initial LCF. CONCLUSION: LCFs provide safe and effective temporary lymphatic decompression in patients with central lymphatic obstruction. While LCFs are not a cure, they can serve as a bridge to more definitive therapies or spontaneous lymphatic remodeling. LEVEL OF EVIDENCE: IV.

Lung biopsy in infants with severe bronchopulmonary dysplasia.

INTRODUCTION: Lung biopsy is infrequently performed in the population of infants with severe bronchopulmonary dysplasia (BPD). Yet, its presentation may overlap with other infant diffuse lung diseases, including those within the spectrum of childhood interstitial lung diseases (chILD). Lung biopsy might differentiate between these entities or identify those with an extremely poor prognosis. Both might alter the clinical management of some infants diagnosed with BPD. METHODS: In this tertiary referral center, we drew on a retrospective cohort of 308 preterm infants with severe BPD. Of these, nine underwent lung biopsy between 2012 and 2017. We aimed to assess the indication for lung biopsy, the prior clinical history, safety of the procedure, and describe the biopsy findings. Finally, we considered management decisions in relation to the biopsy results in these patients. RESULTS: All nine infants undergoing biopsy survived the procedure. The mean gestational age and birth weight of the nine patients were 30 ± 3 (range 27-34) weeks and 1421 ± 571 (range 611-2140) grams. All infants received serial echocardiograms to assess pulmonary hypertension, genetic testing, and computed tomography angiography (CTA) before biopsy. In all nine patients moderate to severe alveolar simplification was present and eight had some degree of pulmonary interstitial glycogenosis (PIG) ranging from focal to diffuse. Following biopsy, two infants with PIG received high dose systemic steroids and two separate infants had care redirected. CONCLUSION: In our cohort, lung biopsy was safe and well tolerated. Findings from lung biopsy may aid decision making in selected patients as a part of a step-wise diagnostic algorithm.

Lymphatic disorders caused by mosaic, activating KRAS variants respond to MEK inhibition.

Central conducting lymphatic anomaly (CCLA) due to congenital maldevelopment of the lymphatics can result in debilitating and life-threatening disease with limited treatment options. We identified 4 individuals with CCLA, lymphedema, and microcystic lymphatic malformation due to pathogenic, mosaic variants in KRAS. To determine the functional impact of these variants and identify a targeted therapy for these individuals, we used primary human dermal lymphatic endothelial cells (HDLECs) and zebrafish larvae to model the lymphatic dysplasia. Expression of the p.Gly12Asp and p.Gly13Asp variants in HDLECs in a 2­dimensional (2D) model and 3D organoid model led to increased ERK phosphorylation, demonstrating these variants activate the RAS/MAPK pathway. Expression of activating KRAS variants in the venous and lymphatic endothelium in zebrafish resulted in lymphatic dysplasia and edema similar to the individuals in the study. Treatment with MEK inhibition significantly reduced the phenotypes in both the organoid and the zebrafish model systems. In conclusion, we present the molecular characterization of the observed lymphatic anomalies due to pathogenic, somatic, activating KRAS variants in humans. Our preclinical studies suggest that MEK inhibition should be studied in future clinical trials for CCLA due to activating KRAS pathogenic variants.

Pathogenic variants in PIK3CA are associated with clinical phenotypes of kaposiform lymphangiomatosis, generalized lymphatic anomaly, and central conducting lymphatic anomaly.

Complex lymphatic anomalies are debilitating conditions characterized by aberrant development of the lymphatic vasculature (lymphangiogenesis). Diagnosis is typically made by history, examination, radiology, and histologic findings. However, there is significant overlap between conditions, making accurate diagnosis difficult. Recently, genetic analysis has been offered as an additional diagnostic modality. Here, we describe four cases of complex lymphatic anomalies, all with PIK3CA variants but with varying clinical phenotypes. Identification of PIK3CA resulted in transition to a targeted inhibitor, alpelisib. These cases highlight the genetic overlap between phenotypically diverse lymphatic anomalies.

Abdominal Surgical Emergencies in Neonates.

Abdominal surgical emergencies are relatively common in neonates. Some of them are related to congenital diseases such as intestinal atresia and intestinal malrotation, whereas some are entirely postnatal conditions such as necrotizing enterocolitis and gastric perforation. While there is a wide range of clinical severity for these conditions, outcomes are most favorable with prompt identification and expeditious treatment. In this review, we describe the most common neonatal abdominal surgical emergencies, highlight the signs that can help with early detection, and explain the approach to diagnosis and management.

Long-term outcomes of bilateral thoracoscopic T3 sympathectomy for primary focal hyperhidrosis in children.

BACKGROUND: Thoracoscopic bilateral T3 sympathectomy for primary focal palmar hyperhidrosis in children has excellent short-term outcomes. However, data in the literature, on the long-term outcomes of the operation are scarce. METHODS: We conducted a retrospective institutional review of all children and adolescents undergoing T3 bilateral thoracoscopic sympathectomy for primary focal palmar hyperhidrosis between June 2013 and October 2020. We composed a quality of life (QoL) questionnaire evaluating the patient's perception of how much the hyperhidrosis affected their daily life in multiple domains. The questionnaire was completed before the operation and at every postoperative follow-up visit. RESULTS: We operated on 58 patients with a median age of 15 (6-25) years. There were no intraoperative or postoperative complications, and all patients had immediate complete postoperative resolution of their palmar hyperhidrosis. Fifty-three patients (91.4%) had long-term follow-up data available with a median of 2.5 (range 0.1-7.5) years. Two patients (3.4%) experienced recurrence of their palmar hyperhidrosis. Nine patients (15.5%) experienced compensatory hyperhidrosis and required occasional medical management with oral anticholinergics. Two patients reported regretting having undergone the operation. Overall, the mean QoL score improved remarkably, from 42/100 before the operation to 92/100 at 1 month, 89/100 at six months to a year, 97/100 between two and four years, and 80/100 ≥ 5 years after the operation. CONCLUSION: Thoracoscopic bilateral T3 sympathectomy has a high success rate for primary palmar hyperhidrosis in children in the mid- to long-term. Compensatory sweating and recurrence can occur years after the operation, so long-term follow up is mandatory. LEVEL OF EVIDENCE: IV.

Bowel perforation following percutaneous sclerotherapy of an intra-abdominal lymphatic malformation.

Mesenteric lymphatic malformations result from abnormal proliferation of disorganized mesenteric lymphatic channels. Sclerotherapy is often preferred over surgery as it is less invasive and has lower post-procedure morbidity. Sclerotherapy has been described as durable and effective with a low complication rate. We describe a serious complication from sclerotherapy of a lymphatic malformation extending from the mesentery through the bowel wall, highlighting the spectrum of this pathology and the need for multidisciplinary management of complex cases.

Dynamic Contrast Magnetic Resonance Lymphangiography Localizes Lymphatic Leak to the Duodenum in Protein-Losing Enteropathy.

OBJECTIVES: Protein-losing enteropathy (PLE) is a disorder of intestinal lymphatic flow resulting in leakage of protein-rich lymph into the gut lumen. Our primary aim was to report the imaging findings of dynamic contrast magnetic resonance lymphangiography (DCMRL) in patients with PLE. Our secondary objective was to use these imaging findings to characterize lymphatic phenotypes. METHODS: Single-center retrospective cohort study of patients with PLE unrelated to single-ventricle circulation who underwent DCMRL. We report imaging findings of intranodal (IN), intrahepatic (IH), and intramesenteric (IM) access points for DCMRL. RESULTS: Nineteen patients 0.3-58 years of age (median 1.2 years) underwent 29 DCMRL studies. Primary intestinal lymphangiectasia (PIL) was the most common referring diagnosis (42%). Other etiologies included constrictive pericarditis, thoracic insufficiency syndrome, and genetic disorders. IN-DCMRL demonstrated a normal central lymphatic system in all patients with an intact thoracic duct and localized duodenal leak in one patient (1/19, 5%). IH-DCMRL detected a duodenal leak in 12 of 17 (71%), and IM-DCMRL detected duodenal leak in 5 of 6 (83%). Independent of etiology, lymphatic leak was only visualized in the duodenum. CONCLUSIONS: In patients with PLE, imaging via DCMRL reveals that leak is localized to the duodenum regardless of etiology. Comprehensive imaging evaluation with three access points can provide detailed information about the site of duodenal leak.

Same-day discharge after laparoscopic appendectomy for non-perforated appendicitis is safe and cost effective.

AIM OF THE STUDY: To compare the outcomes and hospital charges of patients who underwent laparoscopic appendectomy for non-perforated appendicitis and were discharged home either shortly after the operation after being admitted for overnight observation. METHODS: Postoperative (30-day) emergency department (ED) visits, hospital readmissions, and reoperations were compared between patients who were discharged shortly after surgery (same-day discharge [SDD] group) and patients who were discharged after spending one night in the hospital (overnight observation group). STUDY PERIOD: July/2015 to June/2019. Patients with perforated appendicitis and/or who spent > 1 night in the hospital were excluded from the study. RESULTS: We did 1957 laparoscopic appendectomies within the 4-year study period. After excluding all non-eligible cases, 930 patients were included in the overnight observation group, and 511 in the SDD group. Mean age and mean operative time were similar in both groups: 11.5 (SD 3.6)/11.8 (SD 3.5) years, and 35 (SD 13)/33 (SD 12) minutes, respectively. There were 24 (2.6%) ED visits within the overnight observation group. Sixteen patients (1.7%) were discharged from the ED, and 8 (0.9%) required a re-admission. There were 11 (2.1%; P = 0.61) ED visits within the SDD group. Six patients (1.1%; P = 0.41) were discharged from the ED, and 5 (1%; P = 0.82) required a readmission. Six of the 11 ED visits within the SDD group occurred on the 5th postoperative day or later, whereas five (1%) occurred within the first 3 days post appendectomy. These five patients would have likely benefited from an overnight admission and were erroneously discharged on the same day of the appendectomy. There were no reoperations in the overnight observation group, but there were 3 reoperations in the SDD group (0.6%, P = 0.01). The reasons for the reoperations (two bowel obstructions and one bowel perforation) were in no way related to the time of the original discharge. The mean hospital charges per patient in the SDD group and the overnight observation group were significantly different: $32,450 and $35,420, respectively (> 9% margin, P < 0.01). CONCLUSION: Healthy children who undergo laparoscopic appendectomy for non-perforated appendicitis can be discharged home during the same day of the operation after a short period of observation. This approach is safe and does not result in more postoperative ED visits or hospital readmissions. In addition, there is a significant financial benefit when patients are discharged early. LEVEL-OF-EVIDENCE: Level III-retrospective comparative treatment study.