Protein-Losing Enteropathy in the Failing Fontan: Treatment With Angiotensin Receptor Neprilysin Inhibitor.

Angiotensin receptor neprilysin inhibitor is the standard of care for systolic heart failure in adults. In addition, its use in adults with failing systemic right ventricles and diastolic heart failure is promising. This study reports our experience with this drug for protein-losing enteropathy secondary to Fontan failure in pediatrics.

Impact of veno-venous collaterals on outcome after the total cavopulmonary connection.

OBJECTIVE: To evaluate the prevalence of veno-venous collaterals (VVCs) after total cavopulmonary connection (TCPC) and analyze their impact on outcomes. METHODS: Patients undergoing TCPC between 1994 and 2022 were evaluated. VVCs were identified using angiograms of cardiac catheterizations and their impact on outcomes was analyzed. RESULTS: A total of 635 patients were included. Median age at TCPC was 2.3 (interquartile ranges (IQR): 1.8-3.3) years. The most frequent diagnosis was hypoplastic left heart syndrome in 173 (27.2%) patients. Prior bidirectional cavopulmonary shunt was performed in 586 (92.3%) patients at a median age of 5.3 (3.6-9.9) months. VVCs were found in 94 (14.8%) patients at a median of 2.8 (0.1-11.8) years postoperatively. The prevalence of VVCs was similar between the dominant right and left ventricle (14.7 vs. 14.9%, p = 0.967). Mean pulmonary artery pressure (16.2 vs. 16.0 mmHg, p = 0.902), left atrial pressure (5.5 vs. 5.7 mmHg, p = 0.480), transpulmonary gradient (4.0 vs. 3.8 mmHg, p = 0.554) and oxygen saturation (81.4 vs. 82.6%, p = 0.103) before TCPC were similar between patients with and without VVCs. The development of VVCs did not affect survival after TCPC (p = 0.161). Nevertheless, VVCs were a risk for the development of plastic bronchitis (PB, p < 0.001). Interventional closure of VVCs was performed in 60 (9.4%) patients at a median of 8.9 (0.6-15.1) years after TCPC, and improvement of oxygen saturation was observed in 66% of the patients. CONCLUSIONS: The prevalence of VVCs after TCPC was 15%. VVCs had no impact on survival following TCPC but were associated with a high prevalence of PB.

Combined Percutaneous Transhepatic Lymphatic Embolization and Peroral Duodenal Mucosal Radiofrequency Ablation to Manage Protein-Losing Enteropathy.

Percutaneous transhepatic lymphatic embolization (PTLE) and peroral esophagogastroduodenoscopy (EGD) duodenal mucosal radiofrequency ablation (RFA) were performed to manage protein-losing enteropathy (PLE) in patients with congenital heart disease (CHD). Five procedures were performed in 4 patients (M/F = 3/1, median age: 49 years [range 31-71 years]). Transhepatic lymphangiography demonstrated abnormal peri-duodenal lymphatic channels. After methylene blue injection through transhepatic access, subsequent EGD evaluation showed methylene blue extravasation at various sites in the duodenal mucosa. Endoscopic RFA of the leakage sites followed by PTLE using 3:1 ethiodized oil to n-butyl cyanoacrylate glue resulted in improved symptoms and serum albumin (pre-procedure: 2.6 g/dL ± 0.2; post-procedure: 3.5 g/dL ± 0.4, p=0.004) over a median follow-up of 16 months (range 5-20). Transhepatic lymphangiography and methylene blue injection with EGD evaluation of the duodenal mucosa can help diagnose PLE. Combined PTLE and EGD-RFA can be considered to treat patients with PLE.

Comprehensive nutrition guidelines and management strategies for enteropathy in children.

Protein-losing enteropathy (PLE) describes a syndrome of excessive protein loss into the gastrointestinal tract, which may be due to a wide variety of etiologies. For children in whom the protein loss is associated with lymphangiectasia, medical nutrition therapy focused on restricting enteral long-chain triglycerides and thus intestinal chyle production is an integral component of treatment. This approach is based on the principle that reducing intestinal chyle production will concurrently decrease enteric protein losses of lymphatic origin. In patients with ongoing active PLE or those who are on a fat-restricted diet, particularly in infants and young children, supplemental calories may be provided with medium-chain triglycerides (MCT). MCT are absorbed directly into the bloodstream, bypassing intestinal lymphatics and not contributing to intestinal chyle production. Patients with active PLE or who are on dietary fat restriction should be monitored for associated micronutrient deficiencies. In this paper, we seek to formally present recommended nutrition interventions, principles of dietary education and patient counseling, and monitoring parameters in pediatric populations with PLE based on our experience in a busy clinical referral practice focused on this population.

Lymphatic Interventions in Congenital Heart Disease.

Lymphatic disorders in congenital heart disease can be broadly classified into chest compartment, abdominal compartment, or multicompartment disorders. Heavily T2-weighted noninvasive lymphatic imaging (for anatomy) and invasive dynamic contrast magnetic resonance lymphangiography (for flow) have become the main diagnostic modalities of choice to identify the cause of lymphatic disorders. Selective lymphatic duct embolization (SLDE) has largely replaced total thoracic duct embolization as the main lymphatic therapeutic procedure. Recurrence of symptoms needing repeat interventions is more common in patients who underwent SLDE. Novel surgical and transcatheter thoracic duct decompression strategies are promising, but long-term follow-up is critical and eagerly awaited.

Intravenous iron infusion ameliorates anaemia and protein-losing enteropathy in patients after Fontan surgery: case series.

Protein-losing enteropathy is a severe complication of Fontan surgery and is associated with anaemia. Few studies have reported on the efficacy of an intravenous iron infusion for treating protein-losing enteropathy and low albuminemia after Fontan surgery. Herein, we present two cases of female patients who suffered from protein-losing enteropathy and low albuminemia following Fontan surgery, both of whom improved after an intravenous iron infusion.

A case of gaucher disease with a rare complication of gaucheroma and protein-losing enteropathy.

This case report describes a patient initially diagnosed with Gaucher disease (GD) with type I with homozygous mutation c.1448T > C p. (Leu483Pro) at age of 2, presenting with hepatosplenomegaly and cytopenia. Imiglucerase replacement therapy was initiated. At age 17, bilateral hearing loss developed, with subsequent Cranial MRI revealing thalamic damage, leading to a reclassification as type 3 GD. By age of 20, the patient presented with a range of symptoms, including abdominal pain, diarrhea, hypoproteinemia, multiple lymphadenopathy, edema, and Gaucher cell infiltration in the lymph nodes. Comprehensive diagnosis identifies Gaucher tumor and protein-losing enteropathy. Imiglucerase therapy at 90-120 U/kg every 2 weeks significantly improved clinical symptoms, emphasizing the importance of tailored interventions for managing GD manifestations.

Waldmann's disease: Primary intestinal lymphangiectasia diagnosed by 99mTc-labeled albumin macroaggregate scintigraphy-A case report in an adult patient.

Key Clinical Message: Rare yet significant, this case sheds light on the uncommon presentation of Waldmann's disease in adults, showcasing the diagnostic challenges it poses. A multidisciplinary approach, integrating clinical, endoscopic, histological, and radiological evaluations, is crucial for accurate diagnosis and management. Further research is needed to deepen our understanding of this complex disorder. Abstract: Waldmann's disease, or primary intestinal lymphangiectasia, is a rare disorder characterized by protein-losing enteropathy due to dilation and leakage of intestinal lymphatic vessels. Although typically diagnosed in early childhood, we present a case of a 55-year-old male with a complex medical history. The patient's history included intestinal obstruction, multidrug-resistant pulmonary tuberculosis, and primary antiphospholipid syndrome. He presented with a 2-year history of chronic diarrhea, weight loss, and lower limb edema. Endoscopic and histological examination revealed scattered white spots in the duodenum and terminal ileum, indicative of intestinal lymphangiectasia. Nuclear medicine studies confirmed abnormal protein loss. The rarity of Waldmann's disease in adulthood and its association with other significant medical conditions pose diagnostic challenges. The distinct endoscopic and histological findings, coupled with scintigraphy results, contribute to a comprehensive understanding of this complex case. Differential diagnoses and management considerations are discussed. This case highlights the atypical presentation of Waldmann's disease in adulthood, emphasizing the importance of a multidisciplinary approach for accurate diagnosis and management. Further research is warranted to enhance our understanding of this uncommon disorder and its potential implications for patients with complex medical histories.

Successful treatment of lupus protein-losing enteropathy with belimumab: A case report.

Lupus protein-losing enteropathy (LUPLE) is a rare condition in patients with systemic lupus erythematosus (SLE). Since the causes and exact pathological mechanism have not been elucidated, appropriate treatment has not been determined. Here, we report the case of a 69-year-old woman with systemic lupus erythematosus who developed LUPLE which was successfully treated with belimumab without an increase in glucocorticoid dose. This case suggests that belimumab monotherapy may be a treatment option for LUPLE.

The Great Mimicker of Gastric Cancer: A Case Report of Ménétrier's Disease.

This is the case of a 52-year-old Indian lady who presented with hematemesis, severe anemia, and an abdominal lump in cardiac failure. On radiographic evaluation, the lesion appeared to be gross circumferential asymmetric proximal gastric wall thickening, with suspicion of gastric lymphoma or tubercular hypertrophic gastritis. After stabilization with multiple transfusions, she underwent proximal D2 gastrectomy with esophago-gastric anastomosis and a total splenectomy. Grossly, the gastric rugae appeared to be hypertrophied and firm. No growth was identified grossly; however, necrotic areas were identified at the distal end. Microscopic examination of multiple sections studied showed significant foveolar hyperplasia, tortuous glands, and a few cystically dilated foveolar glands, which were limited up to the muscle layer. Mild serosal congestion was seen. No atypia or invasion was seen. An impression to consider is the possibility of Ménétrier's disease (MD). MD is an acquired protein-losing enteropathy with giant gastric rugal folds, decreased acid secretion, and increased gastric mucous production. Radiographically, endoscopically, and grossly, the condition can be confused with malignant lymphoma or carcinoma. It is difficult to diagnose, and histopathological confirmation of the resected specimen is needed for a definitive diagnosis. Our intention in presenting this case is to emphasize that MD can present as massive hematemesis and should be considered in a differential diagnosis. Surgical treatment by total or partial gastrectomy is recommended for cases with persistent, debilitating symptoms or a risk of cancer.

Cytomegalovirus Duodenitis Causing Persistent Hypoalbuminemia and Ascites After Liver Transplantation.

A 44-year-old male had persistent hypoalbuminemia and ascites after liver transplantation. Imaging of the liver and gastrointestinal system was normal. Urine examination was negative for proteinuria. A diagnosis of protein-losing enteropathy was suspected, and a duodenal biopsy was done. Duodenal biopsy was positive for cytomegalovirus (CMV). The patient improved with CMV treatment.

Experience of primary intestinal lymphangiectasia in adults: Twelve case series from a tertiary referral hospital.

BACKGROUND: While primary intestinal lymphangiectasia (PIL) is considered a rare condition, there have been several reported cases in adults. Nevertheless, the absence of clear guidance from diagnosis to treatment and prognosis poses challenges for both physicians and patients. AIM: To enhance understanding by investigating clinical presentation, diagnosis, treatment, complications, and prognoses in adult PIL cases. METHODS: We enrolled adult patients diagnosed with PIL between March 2016 and September 2021. The primary outcome involved examining the diagnosis and treatment process of these patients. The secondary outcomes included identifying complications (infections, thromboembolism) and assessing prognoses (frequency of hospitalization and mortality) during the follow-up period. RESULTS: Among the 12 included patients, peripheral edema (100%) and diarrhea (75%) were the main presenting complaints. Laboratory tests showed that all the patients exhibited symptoms of hypoalbuminemia and hypogammaglobulinemia. Radiologically, the predominant findings were edema of the small intestine (67%) and ascites (58%). The typical endoscopic finding with a snowflake appearance was observed in 75% of patients. Among the 12 patients, two responded positively to octreotide and sirolimus, and eight who could undergo maintenance therapy discontinued subsequently. Complications due to PIL led to infection in half of the patients, thromboembolism in three patients, and one death. CONCLUSION: PIL can be diagnosed in adults across various age groups, with different severity and treatment responses among patients, leading to diverse complications and prognoses. Consequently, tailored treatments will be necessary. We anticipate that our findings will contribute to the management of PIL, an etiology of protein-losing enteropathy.

Recurrent protein-losing enteropathy complicated by postural right subclavian vein compression and right-sided thoracic duct.

We report the case of a 16-year-old female patient with protein-losing enteropathy that was suspected to be caused by thoracic duct congestion associated with postural compression of right subclavian vein. Non-contrast magnetic resonance lymphangiography showed that the thoracic duct connected to the right-sided venous angle of the right subclavian vein which was obstructed when her right arm was lifted. In this case, comprehensive screening of the lymphatics using non-contrast magnetic resonance lymphangiography, which is a minimally invasive tool with high spatial resolution, was helpful for the recognition of the specific pathophysiology. Learning objective: Lymphatic disorders associated with congenital heart disease can be fatal. The morphology and dysfunction of the lymphatic system are complicated, and when added to the complex hemodynamics inherent to congenital heart disease, the pathophysiology is more difficult to understand. To understand the complexity of the lymphatic disease, it is necessary to learn a systematic diagnostic process of lymphatic disorders. In the present case, it is beneficial to know the usefulness of non-contrast magnetic resonance lymphangiography to screen overall lymphatics.

The effect of albumin and total protein values as nutritional markers after Fontan surgery on prognosis.

INTRODUCTION: Children with CHD develop heart failure due to increased pulmonary blood flow, cyanosis, and pulmonary hypertension. The metabolic needs of these children differ from those of healthy children, and malnutrition is common. Protein-losing enteropathy has been reported in 5 to 13% of patients after the Fontan procedure. Serum albumin and total protein levels, which are indicators of the quality of post-operative care, can be useful tools for monitoring and examining the intensive care treatment strategies of these patients. In our retrospective study, the effects of albumin and total protein values, which are two of the markers that give us an idea about diet, nutritional status, and inflammation, on the prognosis of children who underwent the Fontan procedure were investigated. METHOD: In our study, 127 patients who underwent Fontan procedure in our clinic between 2012 and 2021 were analysed retrospectively. Of the patients, 52.7% (n = 67) were male and 47.3% (n = 60) were female. The mean age is 5.83 ± 4.63 years. Patients who underwent albumin replacement were not included in the study. RESULTS: Although the relationship between pre-operative albumin and total protein values and post-operative mortality was not statistically significant, the inverse correlation of post-operative albumin 1st, 2nd, and 3rd-day values and post-operative total protein 1st, 2nd, and 3rd-day values with mortality was found to be statistically significant. In addition, we found that mortality was statistically high in patients whose total protein amount was below 6.65 mg/dl in the early post-operative period. CONCLUSION: Albumin and total protein, whose blood levels can vary with diet, can be used as predictors in the early post-operative prognosis of Fontan patients. In addition, when we examined the exitus patients, it was observed that the total protein amount was below 6.65 mg/dl on the post-operative 1st day. Based on this, we think that a diet with high protein content before surgery will help reduce post-operative early mortality.

Seizure caused by Hypocalcemia as a Rare Manifestation in an Infant with Eosinophilic Gastroenteritis.

Eosinophilic gastroenteritis (EGE) can occur throughout the gastrointestinal tract, from the stomach to the colon. Typical known symptoms are abdominal pain, nausea, vomiting, and diarrhea. In addition, lesions in the intestinal mucosa may cause weight loss, protein-losing enteropathy (PLE), and other problems. A 6-month-old girl with no previous medical history was brought to our hospital after an afebrile 1-min clonic seizure. Blood tests showed low concentrations of serum calcium and albumin. After the correction of hypocalcemia with gluconic acid, there was no recurrence of seizure. Technetium-99m scintigraphy showed slight leakage of protein from the intestinal tract, which led us to conclude that the hypocalcemia and hypoalbuminemia were caused by PLE. Gastrointestinal endoscopy and biopsy performed to detect the cause of PLE revealed the presence of EGE. After starting administration of an amino acid-based formula, gastrointestinal symptoms of diarrhea or vomiting did not reappear. The serum albumin concentration normalized, and her weight gain improved. We report the first case of EGE in an infant who was diagnosed based on seizure. This case shows that infants with EGE may present with seizure resulting from hypocalcemia caused by PLE.

Use of octreotide for the treatment of protein-losing enteropathy in dogs: Retrospective study of 18 cases.

BACKGROUND: More than 50% of dogs with protein-losing enteropathy (PLE) fail to respond to standard therapies. Octreotide, a somatostatin analogue, is used in cases of intestinal lymphangiectasia (IL) in humans with some success. OBJECTIVES: Describe the use of octreotide in dogs with PLE including reason for and details of prescription, adverse effects, and apparent response. ANIMALS: Eighteen dogs with PLE, 13 with histopathology available. Ninety-two percent (12/13) had IL diagnosed on biopsy. All 13 dogs had intestinal inflammatory infiltrates noted. METHODS: Multicenter, retrospective, descriptive study. Cases were volunteered for inclusion by individual attending veterinarians who reported the use of octreotide in cases of PLE. RESULTS: In 16/18 (89%) cases octreotide was prescribed to PLE dogs with a clinical suspicion or confirmed diagnosis of IL that were refractory to standard therapies. Median serum albumin at the time of octreotide prescription was 1.7 g/dL (range, 1.0-3.1 g/dL). The median dose of octreotide prescribed was 20 µg/kg, SQ, daily with a range of 4-39 µg/kg, SQ, daily. Adverse effects were noted in 3/18 (17%, 95% CI [4%, 41%]) of dogs; discontinuation of the drug was necessary in 1 dog. Improvement in clinical signs was noted in 6/12 (50%, 95% CI [21%, 79%]). CONCLUSIONS AND CLINICAL IMPORTANCE: Octreotide was most commonly prescribed to dogs with PLE and suspected or confirmed IL that had failed to respond to standard therapies. Though a benefit to PLE dogs cannot be confirmed, octreotide was well tolerated by the majority of dogs at the doses prescribed in this study.

Dysbiosis of gut microbiota in patients with protein-losing enteropathy after the Fontan procedure.

BACKGROUND: There is a lack of predictive biomarkers for the onset or activity of protein-losing enteropathy (PLE), a Fontan procedure-associated complication. Here, we aimed to identify the gut microbiota composition of patients with active PLE and investigate its relationship with PLE activity. METHODS: This multicenter case-control study involved patients who developed PLE (n = 16) after the Fontan procedure and those who did not (non-PLE; n = 20). Patients with PLE who maintained a serum albumin level of ≥3 g/dL for >1 year were included in the remissive-stage-PLE group (n = 9) and those who did not maintain this level were included in the active-PLE group (n = 7). 16S rRNA gene sequencing analysis of fecal samples was performed using QIIME2 pipeline. Alpha (Shannon and Faith's phylogenetic diversity indices) and beta diversity was assessed using principal coordinate analysis based on unweighted UniFrac distances. RESULTS: Shannon and Faith's phylogenetic diversity indices were lower in the active-PLE group than in the remissive-stage- (q = 0.028 and 0.025, respectively) and non-PLE (q = 0.028 and 0.017, respectively) groups. Analysis of beta diversity revealed a difference in the microbiota composition between the active-PLE and the other two groups. Linear discriminant effect size analysis demonstrated differences in the relative abundance of Bifidobacterium and Granulicatella spp., and Ruminococcus torques between patients with active- and those with remissive-stage-PLE. CONCLUSIONS: Gut microbiota dysbiosis was observed in patients with active PLE. Changes in the bacterial composition of the gut microbiota and decreased diversity may be associated with the severity of PLE.

Recurrent cellulitis and bacteremia in a patient with Noonan syndrome: A case report.

A 28-year old Japanese man with Noonan syndrome (NS) presented to our emergency department with painful erythema of the trunk and lower extremities since the previous day. He had been diagnosed with protein-losing enteropathy (PLE) with intestinal lymphangiectasia at age 25 years, and undergone lymphaticovenular anastomosis (LVA) twice. Three episodes of cellulitis of both lower extremities had occurred in the past 2 years. Extensive cellulitis with sepsis was diagnosed and piperacillin/tazobactam was started, which was de-escalated to ceftriaxone. He was discharged after 13 days of antibiotic therapy. After discharge, low-dose trimethoprim-sulfamethoxazole (SMZ-TMP) was started as the primary prophylaxis, but three episodes of cellulitis occurred in the next year and were treated with other antibiotics. NS, an autosomal dominant disease known as a RASopathy, is caused by germline mutations in RAS-MAPK pathway genes. Lymphedema resulting from lymphatic abnormalities is a concomitant manifestation in 20 % of patients with NS, and can be a risk factor for cellulitis. Hypoalbuminemia and hypoglobulinemia associated with PLE facilitate infections such as cellulitis. As a treatment for lymphedema in the extremities, LVA has shown objective and subjective improvements in most patients, and some studies have also reported its efficacy for lymphedema in patients with NS. Targeted molecular therapy with mitogen-activated protein kinase enzyme (MEK) inhibitor is used in treatment of cancers with activation of the RAS/MAPK pathway. MEK inhibitors have recently been tried in patients with RASopathies and severe lymphatic disorders, and can lead to rapid resolution of symptoms.

Protein-losing enteropathy secondary to graft-versus-host disease

Protein-losing enteropathy is a gastrointestinal complication of Graft versus host disease. The clinical presentation can be similar to that of multiple pathologies and represents a diagnostic challenge for clinicians. We report a 23-year-old man with a history of acute lymphoid leukemia that required allogeneic hematopoietic stem cell transplantation that came to evaluation due to anasarca. We report a 23-year-old man with a history of acute lymphoid leukemia who required allogeneic hematopoietic stem cell transplantation and came to evaluation due to anasarca. (AU)

Impact of aortopulmonary collaterals on adverse events after total cavopulmonary connection.

OBJECTIVES: Effects of aortopulmonary collaterals (APCs) on outcomes after the total cavopulmonary connection (TCPC) are unclear. This study evaluated the incidence of APCs before and after TCPC and analysed the impacts of APCs on adverse outcomes. METHODS: A total of 585 patients, who underwent TCPC from 1994 to 2020 and whose preoperative angiographies were available, were included. Pre-TCPC angiograms in all patients were used for the detection of APCs, and post-TCPC angiograms were evaluated in selected patients. Late adverse events included late death, protein-losing enteropathy (PLE) and plastic bronchitis (PB). RESULTS: The median age at TCPC was 2.3 (1.8-3.4) years with a body weight of 12 (11-14) kg. APCs were found in 210 patients (36%) before TCPC and in 81 (14%) after TCPC. The closure of APCs was performed in 59 patients (10%) before TCPC, in 25 (4.2%) at TCPC and in 59 (10%) after TCPC. The occurrences of APCs before and after TCPC were not associated with short-term or mid-term mortality. The APCs before TCPC were associated with chylothorax (P = 0.025), prolonged chest tube duration (P = 0.021) and PB (P = 0.008). The APCs after TCPC were associated with PLE (P < 0.001) and PB (P < 0.001). With APCs following TCPC, freedom from PLE and PB was lower than without (P < 0.001, P < 0.001). CONCLUSIONS: APCs before TCPC were associated with chylothorax, prolonged chest tube duration and PB. APCs after TCPC were associated with both PLE and PB. The presence of APCs might affect the lymph drainage system and increase the incidence of chylothorax, PLE and PB.