Therapeutic Lymphatic Embolization in Pediatric Primary Intestinal Lymphangiectasia.
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ABSTRACT:
SUBMITTER: Kwon Y
PROVIDER: S-EPMC8084696 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:A number of disorders have been described to cause protein losing enteropathy (PLE) in children. Primary intestinal lymphangiectasia (PIL) is one mechanism leading to PLE. Few syndromes are associated with PIL; Hennekam syndrome (HS) is one of them. The principal treatment for PIL is a high protein, low fat diet with medium chain triglycerides supplementation. Supportive therapy includes albumin infusion. Few publications have supported the use of octreotide to diminish protein loss and minimize hypoalbuminemia seen in PIL. There are no publications on the treatment of PIL with octreotide in patients with HS. We report two children with HS and PLE in which we used octreotide to decrease intestinal protein loss. In one patient, octreotide increased serum albumin to an acceptable level without further need for albumin infusions. The other patient responded more dramatically with near normal serum albumin levels and cessation of albumin infusions. In achieving a good response to octreotide in both patients, we add to the publications supporting the use of octreotide in PIL and suggest that octreotide should be tried in patients with PIL secondary to HS. To the best of our knowledge, this is the first case report on the use of octreotide in HS-associated PIL.
| S-EPMC3501785 | biostudies-literature
Project description:BACKGROUND Intestinal lymphangiectasia (IL) is a rare disease characterized by a dilatation of the intestinal lymphatics and loss of lymph fluid into the gastrointestinal tract leading to hypoproteinemia, edema, lymphocytopenia, hypogammaglobinemia, and immunological abnormalities. Iron, calcium, and other serum components (e.g., lipids, fat soluble vitamins) may also be depleted. A literature search revealed more than 200 reported cases of IL. Herein, we report our observations of a patient diagnosed with IL; we also present our conclusion for our review of the published literature. CASE REPORT A 24-year-old male was admitted to Aleppo University Hospital with the complaints of abdominal pain, headache, arthralgia, fever, and rigors. His past medical history was remarkable for frequent episodes of diarrhea, recurrent infections, and swelling in the lower limbs. In addition, he had been hospitalized several times in non-academic hospitals due to edema in his legs, cellulitis, and recurrent infections. In the emergency department, a physical examination revealed a patient in distress. He was weak, dehydrated, pale, and had a high-grade fever. His lower extremities were edematous, swollen, and extremely tender to touch. The overlying skin was erythematous and warm. Moreover, the patient was tachycardic, tacypneic, and moderately hypotensive. The patient was resuscitated with IV fluids, and Tylenol was administered to bring the temperature down. Blood tests showed anemia and high levels of inflammatory markers. The patient's white blood cell count was elevated with an obvious left shift. However, subsequent investigations showed that the patient had IL. Suitable diet modification plans were applied as a long-term management plan. CONCLUSIONS IL is a rare disease of challenging nature due to its systematic effects and lack of comprehensive studies that can evaluate the effectiveness of specific treatments in a large cohort of patients. MCT (medium-chain triglyceride) oils and diet modification strategies are effective in reducing the loss of body proteins and in maintaining near-normal blood levels of immunoglobulins. However, octreotide and MCT oils had no proven role in shrinking edema in our patient.
| S-EPMC4957630 | biostudies-literature
Project description:Lymphangiectasia, an anomalous dilation of lymphatic vessels first described in the 17th century, is frequently associated with chylous effusion, respiratory failure, and high mortality in young patients, yet the underlying molecular pathogenesis and effective treatments remain elusive. Here, we identify an unexpected causal link between MAPK activation and defective development of the lymphatic basement membrane that drives lymphangiectasia. Human pathological tissue samples from patients diagnosed with lymphangiectasia revealed sustained MAPK activation within lymphatic endothelial cells. Endothelial KRASG12D-mediated sustained MAPK activation in newborn mice caused severe pulmonary and intercostal lymphangiectasia, accumulation of chyle in the pleural space, and complete lethality. Pathological activation of MAPK in murine vasculature inhibited the Nfatc1-dependent genetic program required for laminin interactions, collagen crosslinking, and anchoring fibril formation, driving defective development of the lymphatic basement membrane. Treatment with ravoxertinib, a pharmacological inhibitor of MAPK, reverses nuclear-to-cytoplasmic localization of Nfatc1, basement membrane development defects, lymphangiectasia, and chyle accumulation, ultimately improving survival of endothelial KRAS mutant neonatal mice. These results reveal defective lymphatic basement membrane assembly and composition as major causes of thoracic lymphangiectasia and provide a potential treatment.
| S-EPMC9536262 | biostudies-literature
Project description:Congenital pulmonary lymphangiectasia (PL) is a rare developmental disorder involving the lung, and characterized by pulmonary subpleural, interlobar, perivascular and peribronchial lymphatic dilatation. The prevalence is unknown. PL presents at birth with severe respiratory distress, tachypnea and cyanosis, with a very high mortality rate at or within a few hours of birth. Most reported cases are sporadic and the etiology is not completely understood. It has been suggested that PL lymphatic channels of the fetal lung do not undergo the normal regression process at 20 weeks of gestation. Secondary PL may be caused by a cardiac lesion. The diagnostic approach includes complete family and obstetric history, conventional radiologic studies, ultrasound and magnetic resonance studies, lymphoscintigraphy, lung functionality tests, lung biopsy, bronchoscopy, and pleural effusion examination. During the prenatal period, all causes leading to hydrops fetalis should be considered in the diagnosis of PL. Fetal ultrasound evaluation plays a key role in the antenatal diagnosis of PL. At birth, mechanical ventilation and pleural drainage are nearly always necessary to obtain a favorable outcome of respiratory distress. Home supplemental oxygen therapy and symptomatic treatment of recurrent cough and wheeze are often necessary during childhood, sometimes associated with prolonged pleural drainage. Recent advances in intensive neonatal care have changed the previously nearly fatal outcome of PL at birth. Patients affected by PL who survive infancy, present medical problems which are characteristic of chronic lung disease.
| S-EPMC1637094 | biostudies-literature
Project description:Introduction and importancePrimary intestinal lymphangiectasia (PIL) is a rare protein-losing gastroenteropathy of unknown etiology, characterized by impaired lymphatic vessels drainage. The pathological changes in PIL result in usually localized or diffuse dilatation of intestinal lacteals, leading to leakage of lymphatic fluid rich of proteins, lymphocytes, and immunoglobulins into the intestinal lumen. PIL may be asymptomatic or mildly symptomatic in moderate forms of the disease. In some patients, though, the outcome may be poor or even life-threatening. This case report demonstrates the severity of protein malnutrition, in some cases, and the extent of GI tract affected, requiring to start PN early and the need for its continuation as home parenteral nutrition (HPN).Case presentationWe present a case of 39-year-old male with Factor V Leiden deficiency, who presented initially with symptoms of malnutrition and anasarca. The diagnosis was confirmed by histopathological findings pathognomonic for PIL from biopsies of the stomach, small intestine and colon.Clinical discussionThe patient was started on low fat, high protein parenteral nutrition from the beginning of the treatment and required a long-term HPN for 3 years, because trials of tapering off and discontinuation of PN led to worsening of the biochemical results and recurrence of symptoms. Patient gradually improved and stabilized with persistent nutritional support.ConclusionsThe presented case report shows the magnitude of nutritional support (HPN) needed for severe PIL patients. HPN offers PIL patients with poor outcome and life-threatening complications a chance to improve and lead a normal life.
| S-EPMC8209671 | biostudies-literature
Project description:Lymphatic filariasis is a debilitating disease that afflicts over 70 million people worldwide. It is caused by the parasitic nematodes Wuchereria bancrofti, Brugia malayi, and Brugia timori. Despite substantial success, efforts to eliminate LF will likely require more time and resources than predicted. Identifying new drug and vaccine targets in adult filariae could help elimination efforts. This study's aim was to evaluate intestinal proteins in adult Brugia malayi worms as possible therapeutic targets. Using short interfering RNA (siRNA), we successfully targeted four candidate gene transcripts: Bma-Serpin, Bma-ShTK, Bma-Reprolysin, and Bma-LAD-2. Of those, Bma-LAD-2, an immunoglobulin superfamily cell adhesion molecule (IgSF CAM), was determined to be essential for adult worm survival. We observed a 70.42% knockdown in Bma-LAD-2 transcript levels 1 day post-siRNA incubation and an 87.02% reduction in protein expression 2 days post-siRNA incubation. This inhibition of Bma-LAD-2 expression resulted in an 80% decrease in worm motility over 6 days, a 93.43% reduction in microfilaria release (Mf) by day 6 post-siRNA incubation, and a dramatic decrease in (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction. Transmission electron microscopy revealed the loss of microvilli and unraveling of mitochondrial cristae in the intestinal epithelium of Bma-LAD-2 siRNA-treated worms. Strikingly, Bma-LAD-2 siRNA-treated worms exhibited an almost complete loss of pseudocoelomic fluid. A luciferase immunoprecipitation system assay did not detect anti-Bma-LAD-2 IgE in the serum of 30 LF patients, indicating that LF exposure does not result in IgE sensitization to this antigen. These results indicate that Bma-LAD-2 is an essential protein for adult Brugia malayi and may be an effective therapeutic target. IMPORTANCE Brugia malayi is a parasitic nematode that can cause lymphatic filariasis, a debilitating disease prevalent in tropical and subtropical countries. Significant progress has been made toward eliminating the disease. However, complete eradication may require new therapeutics such as drugs or a vaccine that kill adult filariae. In this study, we identified an immunoglobulin superfamily cell adhesion molecule (Bma-LAD-2) as a potential drug and vaccine candidate. When we knocked down Bma-LAD-2 expression, we observed a decrease in worm motility, fecundity, and metabolism. We also visualized the loss of microvilli, destruction of the mitochondria in the intestinal epithelium, and loss of pseudocoelomic fluid contents after Bma-LAD-2 siRNA treatment. Finally, we demonstrated that serum from filaria-infected patients does not contain preexisting IgE to Bma-LAD-2, which indicates that this antigen would be safe to administer as a vaccine in populations where the disease is endemic.
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Project description:The phosphoinositide 3-kinase (PI3K) family has multiple vascular functions, but the specific regulatory isoform supporting lymphangiogenesis remains unidentified. Here, we report that deletion of the Pik3r1 gene, encoding the regulatory subunits p85alpha, p55alpha, and p50alpha impairs lymphatic sprouting and maturation, and causes abnormal lymphatic morphology, without major impact on blood vessels. Pik3r1 deletion had the most severe consequences among gut and diaphragm lymphatics, which share the retroperitoneal anlage, initially suggesting that the Pik3r1 role in this vasculature is anlage-dependent. However, whereas lymphatic sprouting toward the diaphragm was arrested, lymphatics invaded the gut, where remodeling and valve formation were impaired. Thus, cell-origin fails to explain the phenotype. Only the gut showed lymphangiectasia, lymphatic up-regulation of the transforming growth factor-beta co-receptor endoglin, and reduced levels of mature vascular endothelial growth factor-C protein. Our data suggest that Pik3r1 isoforms are required for distinct steps of embryonic lymphangiogenesis in different organ microenvironments, whereas they are largely dispensable for hemangiogenesis.
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Project description:The R-Spondin (R-Spo) family regulates WNT signaling and stimulates the proliferation and differentiation of intestinal stem cells (ISCs). R-Spo plays a critical role in maintaining intestinal homeostasis, but endogenous producers of R-Spo in the intestine remain to be investigated. We found that R-Spo3 was the major R-Spo family member produced in the intestine and it was predominantly produced by CD45-CD90+CD31+ lymphatic endothelial cells (LECs) in the lamina propria of the intestinal mucosa. Transcriptome analysis demonstrated that LECs highly expressed R-Spo receptor, Lgr5, suggesting an autocrine stimulatory loop in LECs. LECs were significantly reduced in number, and their R-Spo3 production was impaired in intestinal graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation. The impaired production of R-Spo3 in the intestine may be a novel mechanism of delayed tissue repair and defective mucosal defense in intestinal GVHD. We demonstrate a novel role of intestinal LECs in producing R-Spondin3 to maintain intestinal homeostasis.
| S-EPMC6048029 | biostudies-literature
Project description:BackgroundBronchial Dieulafoy's disease (BDD) is a vascular malformation characterized by the presence of a dysplastic artery in the bronchial submucosa. It is very rare in children but potentially fatal due to life-threatening hemoptysis.Case descriptionAn 8-year-old boy and a 6-year-old girl were referred to our hospital with recurrent moderate to massive hemoptysis. Intraluminal protrusions with a tendency to bleed were found by bronchoscopy in both patients. Computed tomography angiography (CTA) revealed an abnormal bronchial artery in one patient and a small intraluminal nodule with contrast enhancement in the other. An enlarged bronchial artery and bronchial-to-pulmonary fistulae corresponding to the lesion site were detected by bronchial arteriography in both patients. Based on the radiological findings, the diagnosis of BDD was established. Subsequent bronchial artery embolization (BAE) was successful, and no recurrence of hemoptysis was observed during the 15- to 18-month follow-up.ConclusionsOur cases highlighted the importance of considering BDD in the context of hemoptysis and endobronchial protrusion in children. Bronchial arteriography plays a critical role in diagnosis, especially in cases where CTA does not reveal vascular malformations. Early identification is essential as biopsy is contraindicated. BAE may be an appropriate treatment to improve the prognosis of children with BDD.
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Project description:Primary sclerosing cholangitis (PSC) is an autoimmune disease characterized by chronic cholestasis, a persistent inflammation of the bile ducts that leads to sclerotic occlusion and cholestasis. Gut microbes, consisting of microorganisms colonized in the human gut, play an important role in nutrient intake, metabolic homeostasis, immune regulation, and immune regulation; however, their presence might aid PSC development. Studies have found that gut-liver axis interactions also play an important role in the pathogenesis of PSC. Patients with PSC have considerably reduced intestinal flora diversity and increased abundance of potentially pathogenic bacteria. Dysbiosis of the intestinal flora leads to increased intestinal permeability, homing of intestinal lymphocytes, entry of bacteria and their associated metabolites, such as bile acids, into the liver, stimulation of hepatic immune activation, and promotion of PSC. Currently, PSC effective treatment is lacking. However, a number of studies have recently investigated the targeted modulation of gut microbes for the treatment of various liver diseases (alcoholic liver disease, metabolic fatty liver, cirrhosis, and autoimmune liver disease). In addition, antibiotics, fecal microbiota transplantation, and probiotics have been reported as successful PSC therapies as well as for the treatment of gut dysbiosis, suggesting their effectiveness for PSC treatment. Therefore, this review briefly summarizes the role of intestinal flora in PSC with the aim of providing new insights into PSC treatment.
| S-EPMC9730442 | biostudies-literature