Echocardiographic and Ultrasonographic Parameters Associated with Protein-losing Enteropathy in Patients with Fontan Physiology: a Systematic Review with Meta-analysis

Abstract Background: Fontan circulation can be associated with significant morbidity, especially Protein-Losing Enteropathy (PLE). Echocardiographic parameters can provide valuable diagnostic information about a patient's risk of developing PLE after Fontan surgery. Objectives: To describe echocardiographic/ultrasonographic parameters associated with PLE in patients after Fontan surgery through a systematic review with meta-analysis. Methods: A literature search was performed in electronic databases to identify relevant studies about echocardiographic parameters and PLE prediction in children after Fontan surgery. The search terms used were: "echocardiography", "ultrasonography", "Fontan," and "protein-losing enteropathy". A p < 0.05 was considered statistically significant. Results: A total of 653 abstracts were obtained from electronic databases and bibliographic references. From these, six articles met criteria to be included in the qualitative analysis and three in the quantitative (meta-analysis). The resistance index in the superior mesenteric artery was described in three studies, and the quantitative analysis showed statistical significance (p < 0.001). Other echocardiographic and ultrasonographic parameters were also described, albeit in single studies not allowing a meta-analysis. Conclusion: This systematic review with meta-analysis identified echocardiographic and ultrasonographic parameters related to PLE in patients with Fontan physiology. Vascular ultrasonography seems to play a prominent role in this aspect, but additional studies are needed to increase the degree of evidence.

Successful Treatment of Protein-Losing Enteropathy After Superior Mesenteric Artery Occlusion without Surgery.

BACKGROUND Protein-losing enteropathy as a complication of superior mesenteric artery occlusion is extremely rare and severe, and sometimes requires intestinal resection. However, the ideal treatment strategy has not yet been determined. CASE REPORT A 77-year-old man with underlying hypertension and diabetes was admitted to the Emergency Department with acute abdominal pain after eating. Contrast-enhanced computed tomography revealed complete occlusion of the superior mesenteric artery with thrombosis, and superior mesenteric artery occlusion was diagnosed. It was successfully treated with interventional therapy, followed by continuous intra-arterial prostaglandin E1 infusion and continuous intravenous heparin infusion. However, the patient developed hypoproteinemia and diarrhea about 10 days after the interventional therapy. Colonoscopy and X-ray studies did not reveal any abnormal findings; however, technetium-99m-labeled human serum albumin scintigraphy indicated protein-losing enteropathy. With total parenteral nutrition and protein-rich oral nutrition, with protein intake at twice the amount in a standard diet, serum albumin improved from 15 g/L to 32 g/L after treatment. Additionally, we administered diuretics to avoiding edema related to the hypoproteinemia. The patient recovered from the hypoproteinemia and diarrhea without complications. CONCLUSIONS Protein-losing enteropathy is an extremely rare but critical complication of superior mesenteric artery occlusion. Treating the underlying pathology is the mainstay of protein-losing enteropathy and dietary modifications also play a critical role. Our patient was successfully treated with strict nutritional therapy, combined oral protein-rich nutrition and total parenteral nutrition, which avoided surgery.

Therapeutic Lymphatic Embolization in Pediatric Primary Intestinal Lymphangiectasia.

Primary intestinal lymphangiectasia (IL) can cause leakage of lymphatic fluids into the gastrointestinal tract, eventually leading to protein-losing enteropathy. A 15-year-old male patient, whose disease began at the age of 8 years, recently felt worsening general weakness. After diagnosing abnormal lymphatic lesions in the duodenum through endoscopy with biopsy and contrast-enhanced magnetic resonance lymphangiography, glue embolization of the leaking duodenal lymphatic channel was successfully performed. This procedure is typically reserved for adult patients, although as shown in this case, it can be properly performed in children. His serum albumin level was initially 1.5 g/dL, but elevated to 5.0 g/dL after two sessions of lymphatic embolization. Accordingly, we suggest that embolization could potentially be considered a first-line treatment for focal lesions of primary intestinal IL.

Abdominal Imaging of Children and Young Adults With Fontan Circulation: Pathophysiology and Surveillance.

OBJECTIVE. The Fontan procedure has significantly improved the survival in children with a functional single ventricle, but it is associated with chronically elevated systemic venous pressure that leads to multisystemic complications. Imaging plays an important role in assessing these complications and guiding management. The pathophysiology, imaging modalities, and current surveillance recommendations are discussed and illustrated. CONCLUSION. Significant improvement in survival of patients with Fontan circulation is associated with ongoing cardiac and extracardiac comorbidities and multisystemic complications. The liver and intestines are particularly vulnerable to damage. In addition, this patient population has been shown to be at increased risk of certain malignancies such as hepatocellular carcinoma and neuroendocrine tumors. Familiarity with imaging findings of Fontan-associated liver disease and other abdominal complications of the Fontan circulation is essential for radiologists because we are likely to encounter these patients in our general practice.

The diagnostic value of capsule endoscopy in children with intestinal lymphangiectasia.

BACKGROUND: intestinal lymphangiectasia is an unusual cause of protein-losing enteropathy due to either congenital malformation or obstruction of the intestinal lymphatics. However, few reports have investigated the use of video capsule endoscopy in children with intestinal lymphangiectasia. This study was performed to evaluate the diagnostic value of video capsule endoscopy for pediatric intestinal lymphangiectasia. METHODS: in this retrospective study, all patients who underwent video capsule endoscopy between January 2014 and July 2020 were included. Clinical information and video capsule endoscopy data were analyzed. RESULTS: twelve children were enrolled, 7 males and 5 females, with an age at disease onset of 4.5 (range: 3.2-9.3) years and a disease duration of 12.0 (range: 1.3-30.0) months. The most common symptoms were hypoproteinemia (10, 83.3 %), diarrhea (7, 58.3 %), edema (6, 50.0 %), and abdominal pain (3, 25.0 %). Eight patients had low lymphocyte counts, whereas 10 had reduced serum albumin levels (23.2 ± 5.8 g/L). Video capsule endoscopy revealed an overall white snowy appearance due to the presence of whitish, swollen villi in all patients. Regarding the macroscopic lesions of lymphangiectasia, 7 cases involved the entire small bowel from the duodenum to the ileocecal valve, while 5 cases involved part of the small bowel. All patients were treated with medium-chain triglyceride diets, and albumin infusions were administered to 10 patients; sirolimus treatment was administered to 3 patients. At the last follow-up, 5 patients still had hypoalbuminemia and one patient had died of intestinal lymphoma. CONCLUSION: video capsule endoscopy is useful for the diagnosis of intestinal lymphangiectasia and should be applied as a valuable and less invasive examination to confirm or establish a diagnosis.

Revascularization of Isolated Superior Mesenteric Artery Dissection for Post-Mesenteric Infarction Exudative Enteropathy: The Contribution of a Multidisciplinary Care Teamwork.

BACKGROUND: Isolated dissection of the superior mesenteric artery (SMA) is increasingly diagnosed; the conservative treatment appears to be the best option when blood supply is maintained. However, some patients require a more invasive attitude, due to acute or chronic ischemic complication. Multidisciplinary care within a health-care network improves medical and surgical support. We present a case of chronic complication of isolated SMA dissection requiring a revascularization, followed by bowel resection. CASE PRESENTATION: A 49-year-old man presented abdominal pain secondary to necrotizing enterocolitis of unknown cause. An isolated small bowel resection with immediate restoration of continuity was first performed to remove the necrotic tissue. The patient developed post-ischemic exudative enteropathy and small intestinal bacterial overgrowth (SIBO). Re-examination of the first computed tomography (CT) scan revealed an isolated dissection of the SMA that had not been diagnosed. The patient was then successfully treated by superior mesenteric revascularization, and after recovering, he underwent small bowel resection for chronic ischemia. CONCLUSIONS: SMA revascularization has to be performed in case of SMA dissection complicated of bowel ischemia. Enteropathy is a rare complication of chronic mesenteric ischemia requiring digestive and vascular management in a dedicated health-care team.

Protein losing gastroenteropathy due to Helicobacter pylori infection without giant rugal folds, erosion or polyposis.

An 85-year-old woman was admitted to our hospital because of progressive hypoproteinemia and generalised oedema. Technetium-99m human albumin scintigraphy revealed protein leakage in the gastrointestinal tract. Upper gastrointestinal endoscopy revealed small whitish nodules from the gastric body up to the duodenal bulb. The urease test for Helicobacter pylori infection was positive. We diagnosed her as having protein-losing gastroenteropathy (PLGE) caused by H. pylori infection. The patient's hypoproteinemia and clinical symptoms promptly resolved after H. pylori eradication. Our results suggest that a trial of H. pylori eradication is warranted in patients with PLGE, even if endoscopy reveals neither giant rugal folds, erosion of the mucosa, nor polyposis, which are previously reported characteristic endoscopic findings of PLGE.

Protein-losing enteropathy in a patient with familial adenomatous polyposis and advanced colon cancer.

A 29-year-old female visited a hospital because of increasingly severe lower leg edema. She was diagnosed as having multiple polyps in the stomach and colon by gastroscopy and sigmoidoscopy as well as multiple liver tumors by abdominal CT. She was referred to our hospital for further examination. Total colonoscopy revealed a type 2 tumor in the transverse colon and more than 200 polyps distributed throughout the colorectum. Biopsies of the tumor and polyps showed histological characteristics of adenocarcinoma and tubulovillous adenoma, respectively. Thus, she was diagnosed as having metastatic colon cancer derived from familial adenomatous polyposis (FAP). Laboratory tests showed a marked hypoalbuminemia of 1.1 g/dl. The fecal alpha-1 anti-trypsin test showed abnormal clearance (62.1 ml/day), and scintigraphy using 99mTc-human serum albumin revealed protein loss in the whole colon. Multiple ligation probe amplification analysis of the APC gene identified a germline duplication of exons 11-13. Direct sequencing of the reverse transcription PCR products of APC mRNA revealed a deletion of 25 base pairs and a tandem duplication of exons 11-13. This case was considered to be protein-losing enteropathy resulting from numerous colonic tubulovillous adenomas and advanced colon cancer in a FAP patient with unusual mutational events in APC.

Early Impact of Fontan Operation on Enteric Protein Loss.

BACKGROUND: Protein-losing enteropathy (PLE) is a challenging complication after a Fontan operation. Subclinical enteric protein loss may precede development of overt PLE. We evaluated the acute effects of Fontan circulation on enteric protein loss and mesenteric vascular resistance. METHODS: A prospective cohort study was performed evaluating enteric protein loss in children undergoing Fontan operations. Stool alpha-1 antitrypsin (A1AT) concentration was measured in the preoperative, early postoperative, and intermediate postoperative (3-9 months) periods. The intestinal circulation was characterized by Doppler-derived resistance indices of the superior mesenteric artery (SMA), and serum albumin and protein levels were obtained. RESULTS: We enrolled 33 participants at a median age at operation of 3.0 years (interquartile range [IQR], 2.5-3.3 years). No clinical PLE was observed. Six of the 93 stool samples obtained had elevated A1AT levels (>54 mg/dL), with 2 abnormal samples at each of the 3 time points. Two of the 5 participants with elevated stool A1AT values had significant hemodynamic disturbances requiring intervention (junctional bradycardia or tricuspid stenosis). There was no difference in SMA resistance in the preoperative versus early postoperative periods (p = 0.9). Serum albumin levels were lower in the early postoperative period compared with the preoperative period (3.2 mg/dL [{IQR}, 2.9-3.5] versus 4.1 mg/dL; IQR, 3.4-4.5; p = 0.01) but did not correlate with abnormal stool A1AT concentration or SMA resistance indices. CONCLUSIONS: The Fontan operation does not commonly result in acute development of increased enteric protein loss. However, increased enteric protein loss may occur in children before or after a Fontan operation, particularly when hemodynamic disturbances are present.

Focal intestinal lipogranulomatous lymphangitis in 6 dogs (2008-2011).

BACKGROUND: Lipogranulomatous lymphangitis is inflammation of the intestinal lymphatic vessels and surrounding tissues caused by chronic leakage of lipid-laden chyle. Grossly, lipogranulomas are typically disseminated small masses on the serosa and surrounding lymphatic vessels and consist of epithelioid macrophages, multinucleated giant cells, and cholesterol. Lipogranulomatous lymphangitis is occasionally seen in patients with lymphangiectasia and protein-losing enteropathy (PLE). OBJECTIVES: To characterize the historical features, clinical signs, treatment, histopathology, and outcome of dogs with focal lipogranulomatous lymphangitis. ANIMALS: Six dogs with ultrasonographic evidence of focal, regional small intestinal masses, often with involvement of the adjacent mesentery, and a diagnosis of focal lipogranulomatous lymphangitis based on histopathology of biopsied masses. RESULTS: The median age of dogs was 6.9 years (range 3-10 years). All dogs had total protein, globulin, and albumin concentrations within the reference range at initial presentation and had intestinal masses identified on abdominal ultrasound examination. Histopathologic evaluation of lesions identified severe mural and mesenteric lipogranulomatous lymphangitis. Lymphangiectasia was noted in 5 cases and only in sections within the mass-like lesion; tissue without lipogranulomas had minimal lymphangiectasia, suggesting a localized phenomenon. Postoperative outcomes ranged from remission of clinical signs with no subsequent treatment for 10-12 months in 2 dogs, postoperative management with medical and nutritional management in 3 dogs, and no outcome for 1 case. CONCLUSIONS AND CLINICAL IMPORTANCE: This case series describes a unique mass-like manifestation of intestinal lipogranulomatous lymphangitis and should be considered as a possible differential diagnosis in dogs with an intestinal mass.

Low cardiac output in a case of constrictive pericarditis with protein-losing enteropathy.

A man in his late seventies was suffering from right-sided pleural effusion and worsening leg edema. He was diagnosed with a rare case of secondary protein-losing enteropathy caused by constrictive pericarditis (CP) using technetium 99m-labeled human serum albumin abdominal scintigraphy and comprehensive Doppler echocardiography. We herein report the importance of evaluating a low cardiac output in addition to established Doppler echocardiographic findings for making a diagnosis of CP coexistent with protein-losing enteropathy.

The clinical characteristics of lupus related protein-losing enteropathy in Hong Kong Chinese population: 10 years of experience from a regional hospital.

OBJECTIVE: The aim of our study was to investigate systemic lupus erythematosus (SLE) related protein-losing enteropathy (PLE) in the following areas: clinical features, laboratory, endoscopic and imaging characteristics, treatment and outcome. METHOD: A retrospective analysis was performed. RESULTS: From 2001 to 2010, 48 patients had SLE related PLE and their clinical characteristics were: age 40.8 ± 14.3 years, male-to-female ratio 1:8.6, mean symptom duration 4.3 ± 3.4 weeks, initial presentation and concomitant activity of SLE in 21(43.8%) and 37 (77.1%) patients, <20% patients developed gastrointestinal (GI) symptoms, mean serum albumin level 24.4 ± 5 g/L. Thirty (62.5%) patients had diffuse non-erosive erythematous GI mucosa with chronic inflammatory cells in lamina propria. Protein leakage was at the small bowel in 15 (31.3%) patients, terminal ileum/caecum in 16 (33.3%) patients and ascending colon in 11 (22.9%) patients. Thirty (62.5%) patients responded initially well to a combination of prednisolone and azathioprine (AZA) and 33 (68.8%) patients were maintained well by the above therapy. Higher potent induction and maintenance therapy were required in patients with: proteinuria (p < 0.01), history of previous immunosuppressive therapy (p < 0.02) and requirement of higher potent induction therapy (p < 0.01). PLE as initial SLE presentation was associated with better prognosis. Four reversible adverse events were reported: one had AZA-induced pancreatitis, two developed AZA-induced hypoplastic anemia and one developed steroid psychosis. One patient developed shingles in the fourth month and responded to oral acyclovir. No thromboembolic events were reported and one patient died of SLE nephropathy. CONCLUSION: There appears to be increasing prevalence of SLE related PLE. A diagnosis can be made using 99m Tc-labeled HSA scintigraphy. PLE generally responds well to immunosuppressive therapy.

Intestinal uptake of (99m)Tc-MDP: a case report of protein-losing enteropathy correlated with pathology findings from autopsy.

We present a case of a 60-year-old man with a history of severe hypoproteinemia and constitutional syndrome, suspected to have protein-losing enteropathy (PLE). Bone scintigraphy ((99m)Tc-MDP) performed to rule out the presence of bone metastases incidentally showed abnormal uptake in abdominal soft tissue. The patient unexpectedly died of heart failure, and autopsy revealed microscopic alterations consistent with PLE exclusively in the right colon, corresponding to the area of abnormal uptake. Few similar cases have been published, but none of them reported correlative pathological findings affecting the area of abnormal tracer uptake. In this case of PLE, (99m)Tc-MDP scintigraphy was a useful imaging method for localizing the site of protein loss, showing a focal area of alteration in the right colon. This finding could also have been of great help in case that surgery had been finally performed to control the protein loss.

Protein-losing enteropathy in paracoccidioidomycosis identified by scintigraphy: report of three cases.

Paracoccidioidomycosis (PCM) or South American Blastomycosis is a systemic fungal infection caused by a dimorphic fungus, Paracoccidioides brasiliensis. It represents the most important systemic mycosis in South America and with higher prevalence among male inhabitants of the rural area. PCM usually affects the lungs, and rarely the intestines. The authors report three cases of PCM, treated at the University Hospital of Universidade Federal de Mato Grosso do Sul whose scintigraphy with technetium-99 labeled human albumin revead intestinal protein loss.

Ultrasonographic intestinal hyperechoic mucosal striations in dogs are associated with lacteal dilation.

In this retrospective study, the medical records of 23 dogs with the sonographic feature of small intestinal hyperechoic mucosal striations and an endoscopic or surgical intestinal biopsy were reviewed. Histopathologic lacteal dilation was present in 96% of dogs with mucosal striations. Sonographic findings associated with mucosal striations included: mild jejunal wall thickening (96%), mild duodenal wall thickening (78%), mucosal speckles (70%), and abdominal effusion (87%). The mucosal striations were diffuse (70%) or multifocal (30%) and did not cause loss of wall layering, except in one dog with a severe mural lipogranuloma. Mesenteric lymphadenopathy was identified in 9% of dogs. Thirteen dogs with endoscopic biopsies had mild to moderate villus lacteal dilation and the nine dogs with surgical biopsies had moderate to severe dilation. Inflammatory infiltrates were mild (61%) or moderate (30%) with variable numbers and combinations of cells, including eosinophils (65%), plasma cells (61%), lymphocytes (57%), and neutrophils (30%); one dog had disseminated villus histiocytic sarcoma. The biochemistry changes and clinical signs were consistent with protein-losing enteropathy in 78% of dogs. Hyperechoic mucosal striations in dogs are associated with lacteal dilation and are frequently associated with mucosal inflammation and protein losing enteropathy.

Scintigraphic diagnosis of protein-losing enteropathy secondary to amyloidosis.

Protein-losing enteropathy is an uncommon syndrome of excessive loss of protein via the gastrointestinal mucosa. 99mTc-dextran scintigraphy was performed on a 42-year-old woman with protein-losing enteropathy. She had secondary amyloidosis due to rheumatoid arthritis. Abnormal leakage of the radiotracer was observed in the mid-abdominal region suggesting the site of protein loss. It is concluded that 99mTc-dextran scintigraphy is useful as a noninvasive and simple test for the imaging and confirmation of diagnosis in protein-losing enteropathy.

Severe protein losing enteropathy with intractable diarrhea due to systemic AA amyloidosis, successfully treated with corticosteroid and octreotide.

This report concerns two patients with severe protein losing enteropathy and refractory diarrhea due to AA amyloidosis who were successfully treated with corticosteroid and octreotide. In these patients, biopsied tissues from the gastrointestinal (GI) tract showed extensive deposition of AA amyloid, which was caused by rheumatoid arthritis in one case and was of unidentified etiology in the other. Both patients manifested severe diarrhea unresponsive to conventional treatment with hypoproteinemia, and protein leakage from the small intestine to the ascending colon was confirmed by 99mTc-diethylene triamine pentaacetic acid human serum albumin (HSA-D) scintigraphy. Soon after starting a long-acting somatostatin analogue, octreotide, with co-administration of oral prednisolone, their general status improved in parallel with a rapid decrease in the volume of watery diarrhea and an increase in serum levels of albumin and IgG. Also on 99mTc-HSA-D scintigraphy protein leakage from the GI tract was apparently decreased in both patients. Combination therapy with a somatostatin analogue and corticosteroid may be effective for protein losing enteropathy with intractable diarrhea ascribable to GI amyloidosis. Because of the lack of specific therapies in this serious clinical situation, the described therapy should actively be considered as a therapeutic option not only in AA amyloidosis, but also in other types of systemic amyloidosis.

Application of technetium-99m-labeled human serum albumin scan to assist surgical treatment of protein-losing enteropathy in Cronkhite-Canada syndrome: report of a case.

Cronkhite-Canada syndrome is a rare form of nonhereditary gastrointestinal polyposis associated with ectodermal change and protein-losing enteropathy. Here we report a 63-year-old male presenting with diffuse gastrointestinal polyposis, onychodystrophy, cutaneous pigmentation, alopecia, diarrhea, hypoalbuminemia and lower leg edema. Technetium-99m-labeled human serum albumin scan confirmed the patient to have protein-losing enteropathy, which originated from the transverse and descending colon. Subtotal colectomy was performed. Albumin level and ectodermal change were gradually improved during three years of outpatient clinic follow-up. Based on our finding, Technetium-99m-labeled human serum albumin scintigraphy is helpful to localize the protein-losing origins and surgery is an effective treatment for Cronkhite-Canada syndrome with protein-losing enteropathy.