Association between technetium-99m albumin scintigraphy-based severity of protein-losing enteropathy and patient characteristics and laboratory data

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Methods Eighteen patients with PLE were grouped into two based on two mechanisms: direct mucosal damage and failed lymph drainage. Scintigraphy images were divided based on the timing of acquisition: dynamic images obtained within the first hour; and images obtained at 2, 4, 6, and 24 h after starting the examination. The intensity of tracer uptake was graded as follows: 3 (marked uptake equal to or greater than the liver level), 2 (moderate uptake less than liver and greater than kidney levels), 1 (mild uptake less than kidney level), and 0 (negative). The grades at each timepoint for the two groups were compared using the Mann-Whitney U test. The associations between the grades and fecal alfa-1-antitrypsin and serum total protein concentrations were evaluated using Pearson correlation coefficients. Results Of 18 patients, 7 had PLE due to failed lymph drainage. The direct mucosal damage and failed lymph drainage groups had significantly different fecal alfa-1-antitrypsin concentrations (43.5 ± 29.6 [range, 11–115] vs. 208.7 ± 66.0 [range, 124–311], respectively; P < 0.001) and scintigraphy-based severity at 24 h (1.2 ± 0.8 [range, 1–3] vs. 2.8 ± 0.4 [range, 2–3], respectively; P = 0.007). The fecal alpha-1-antitrypsin concentration was positively correlated with the scintigraphy-based severity at 6 h (r = 0.499, P = 0.049) and 24 h (r = 0.747, P = 0.002). However, the serum protein concentration was negatively correlated with the scintigraphy-based severity at 6 h (r = -0.587, P = 0.017). Conclusions The scintigraphy-based severity at 6 and 24 h and the fecal alpha-1 antitrypsin concentrations were higher for patients with PLE due to failed lymph drainage mechanisms than for those with PLE due to direct mucosal damage. Scintigraphy can help localize the leakage point and determine disease severity to guide PLE management. Protein losing enteropathy Fontan nuclear medicine scintigraphy Technetium-99m Albumin scintigraphy Figures Figure 1 Figure 2 Figure 3 INTRODUCTION Protein-losing enteropathy (PLE) is rare condition characterized by protein loss into the gastrointestinal tract [ 1 – 3 ]. The two principal underlying pathophysiological mechanisms are direct mucosal damage (either erosive or nonerosive) and failed lymph drainage, causing backflow through the epithelium into the lumen [ 3 ]. Patient outcomes and treatment vary based on these mechanisms [ 4 – 7 ]. In addition, the severity of laboratory findings of the patients is associated with PLE recurrence after treatment [ 4 ]. The fecal alpha-1-antitrypsin concentration and technetium-99m albumin scintigraphy findings are important for diagnosing this PLE [ 8 – 14 ]. Fecal alpha-1-antitrypsin is usually the first examination for patients with suspected PLE, and it can predict the amount of protein lost into the intestine [ 3 , 15 , 16 ]. Technetium-99m albumin scintigraphy is also useful for diagnosing PLE, as it helps visualize the tracer in the gastrointestinal tract and detect the leakage point [ 8 – 10 , 12 , 15 , 17 ]. However, systematic studies on the associations of the severity of patient conditions and laboratory data are lacking. Furthermore, few studies have discussed the severity of scintigraphy findings [ 10 ]. The purpose of this study was to demonstrate the differences in Technetium-99m albumin scintigraphy findings for PLE cases secondary to direct mucosal damage and failed lymph drainage. The study also aimed to describe the association between the scintigraphy-based severity of PLE and laboratory data of patients. MATERIAL AND METHODS Ethical considerations This retrospective study was conducted in accordance with the principles of the Declaration of Helsinki. The ethics committee of our institution approved this study and waived the requirement for informed consent due to its retrospective design. Study population We reviewed the medical database of our hospital and included patients with suspected PLE who underwent Technetium-99m albumin scintigraphy between April 2000 and May 2025. Twenty patients were enrolled in this study. Only the results of the first examination were evaluated for patients who underwent this examination multiple times. The exclusion criteria were as follows: unreviewed medical records (n = 2). Patient data Suspected PLE PLE has various symptoms, including hypoproteinemia, edema, nutritional deficiency, and recurrent infection [ 2 , 3 , 10 ] The fecal alpha-1-antitrypsin concentrations were determined for these cases, and a spot value greater than 10 mg/dl indicated PLE positivity or warranted its suspicion. The clearance was better for evaluating the amount of protein lost. However, it was difficult to calculate the protein loss for patients in our hospital using the amount of feces in one day. Patient characteristics and laboratory data Following data were recorded; sex, age of scintigraphy examination, underlying disease associated with PLE and spot value of alfa-1 antitrypsin. In addition, serum albumin and serum protein levels obtained on the same day of scintigraphy examination were recorded. Patient classification Patients were classified into two groups based on the mechanism: direct mucosal damage or failed lymph drainage. Direct mucosal damage includes inflammatory and ulcerative diseases, infections, malignancy, hypertrophic gastropathies, eosinophilic gastroenteropathies, vasculitic disorders. Failed lymph drainage includes primary lymphangiectasia and secondary lymphangiectasia such as obstructive or elevated lymph pressure caused by congenital heart disease or syndrome [ 1 – 3 ]. Technetium-99m albumin scintigraphy Equipment and examination protocol: Technetium-99m Albumin scintigraphy was performed in patients with suspected PLE, who had symptoms such as diarrhea, generalized edema, low serum protein, low serum albumin, or/and high fecal α-1-antitrypsin. Doses of 50 MBq of Technetium-99m labeled human serum albumin-DTPA (99mTc-HSAD) were determined based on the Japanese Society of Nuclear Medicine guidelines (administration dose range 73.1–740 MBq)[ 18 ]. A gamma camera (Siemens Symbia E or T16; Siemens Medical Systems Inc., Hoffmann Estates, IL, USA) equipped with a fan beam collimator was used. A 60-min anterior dynamic sequence captured the dynamic phase (Figs. 3 , 4, 5), followed by the acquisition of static anterior, posterior, and both right and left lateral images at 2, 4, 6, or 24 h post-injection. Previous images could not be obtained in some cases due to those general conditions. For cases with difficulty assessing bowel activity in static images, single-photon emission computerized tomography (SPECT) scans were obtained. The dynamic sequence was obtained with a 64 × 64 matrix size and at sampling times of 30 s. All static images were obtained with a 512 × 512 matrix size and at varying sampling times (300 s at 3 h, 300 s at 6 h, and 900 s at 24 h). Evaluation of scintigraphy results: The examination results were evaluated based on previous studies [ 10 , 14 , 16 ]. The timing of image evaluations varied across studies, which may lead to confusion when comparing the studies [ 10 , 14 , 16 ]. Therefore, we classified the timing of imaging evaluations based on the time of acquisition as follows: dynamic images acquired within the first hour; images obtained at 2 h; images obtained at 4 h; images obtained at 6 h; and images obtained at 24 h after the commencement of the examination. The intensity of tracer uptake in the intestinal tract was graded as follows: 3, marked uptake equal to or greater than that in the liver (Fig. 1 ); 2, moderate uptake less than that in the liver and greater than that in the kidney (Figs. 1 , 2 ); 1, mild uptake less than that in the kidney (Figs. 2 , 3 ); and 0, negative uptake (Figs. 1 – 3 )[ 10 ]). For cases with greater uptake in the kidney than in the liver, marked uptake was defined as equal to or greater than that in the kidney, moderate uptake as less than that in the kidney and greater than that in the liver, and mild uptake as less than that in the liver. The main leakage points of PLE were classified into the small intestine (Figs. 1 , 3 ) and large intestine (Fig. 2 ). The presence (Figs. 1 , 2 ) or absence (Fig. 3 ) of tracer movement to the distal large intestine was evaluated. Review process: Two pediatric radiologists with 25 and 10 years of clinical experience in pediatric nuclear medicine independently reviewed all images of technetium-99m albumin scintigraphy using a 1600 × 1200 picture archiving and communication system (PACS; GE Healthcare). Discrepancies in interpretation between the radiologists were resolved by consensus. Statistical analysis The data are presented as the mean ± standard deviation. Statistical significance was set at P < 0.05 (two-sided) for all tests. All analyses were performed using IBM SPSS Statistics for Windows version 24 (IBM Corp., Armonk, NY, USA). The characteristics of the patients with PLE caused by direct mucosal damage and those with PLE caused failed lymph drainage, including sex, age, and scintigraphy findings such as main leakage point of PLE and presence or absence of tracer movement to distal large intestine, were compared using Fisher’s exact test and the Mann-Whitney U test. The uptake intensities for each timing were compared for the two groups using the Mann-Whitney U test. The associations between those grades and age and serum albumin, serum protein, and fecal alpha-1-antitrypsin concentrations were evaluated using Pearson correlation coefficients. RESULTS Patient characteristics The patient characteristics are summarized in Table 1 . Eighteen patients were enrolled in this study. Of these, 11 had direct mucosal damage, and seven had failed lymph drainage. The underlying diseases or final diagnoses of the 11 patients with direct mucosal damage were enteritis due to infection by unknown pathogens in eight patients, cytomegalovirus infection in one patient, and systemic lupus erythematosus or juvenile idiopathic arthritis in one patient each. Of the seven patients with failed lymph drainage, five had undergone the Fontan operation, and two had right-sided hypertension due to congenital heart disease before the Fontan operation. Nine patients were male and nine were female. Their average age was 6.3 ± 6.7 [range, 0.3–25.5] years. Their average serum total protein, serum albumin, and fecal alpha-1-antitrypsin concentrations were 4.9 ± 1.1 [range, 3.5–7.1] g/dl, 2.6 ± 0.7 [range, 1.6–4.1] g/dl, and 107.8 ± 94.4 [range, 11–311] mg/dl, respectively. Table 1. Patient characteristics No sex Age (years) Serum Albumin (g/dl) Serum protein (g/dl) Fecal alfa-1-antitrypsin (mg/dl) Underlying disease/diagnosis Mechanism of PLE Leakage point Grade of tracer intensity in each timing* Tracer movement into distal large intestine Fig -1 h 2 h 4 h 6 h 24 h 1 M 7.5 2.6 4.8 311 After Fontan operation failed lymph drainage Small intestine 0 2 3 3 3 Present Fig 1 2 M 1.2 3 5.2 269 Right side hypertension before Fontan operation failed lymph drainage Small intestine 0 1 2 ** ** Present 3 M 10.7 2.4 4.6 220 After Fontan operation failed lymph drainage Small intestine 0 ０ 2 3 3 Present 4 F 3.0 2.2 3.8 210 After Fontan operation failed lymph drainage Small intestine 0 0 ０ 2 3 Present 5 M 4.3 2.5 4.3 182 Right side hypertension before Fontan operation failed lymph drainage Large intestine 0 ** ２ 2 ** Absent 6 M 3.6 1.9 3.6 145 After Fontan operation failed lymph drainage Small intestine 2 2 ２ 2 3 Present 7 M 4.3 2.1 4.3 124 After Fontan operation failed lymph drainage Small intestine 2 ２ ３ 3 2 Present 8 M 3.7 1.6 3.5 115 Enteritis due to infection direct mucosal damage Small intestine 0 2 2 3 1 Absent 9 M 3.4 3.5 6.2 60 Enteritis due to infection direct mucosal damage Small intestine 0 0 0 1 2 Present 10 F 25.5 2.3 4.8 57 Enteritis due to infection direct mucosal damage Small intestine 0 0 １ 1 1 Present 11 F 16.2 3.5 5.6 56 Juvenile idiopathic arthritis direct mucosal damage Large intestine 0 ０ ２ 2 1 Present Fig 2 12 F 14.8 2.4 4.4 53 Systematic lupus arthropathy direct mucosal damage Small intestine 2 2 ３ 3 3 Present 13 F 0.3 2.5 4 35 Cytomegalovirus infection direct mucosal damage Small intestine 3 ３ ３ 3 ** Present 14 F 9.1 4.1 7.1 33 Enteritis due to infection direct mucosal damage Small intestine 0 ０ １ 1 1 Present 15 F 2.6 3.3 7 21 Enteritis due to infection direct mucosal damage Small intestine 0 0 １ 1 1 Absent Fig 3 16 M 2.5 3.1 6 21 Enteritis due to infection direct mucosal damage Small intestine 1 2 ** ** ** Present 17 F 0.6 2.1 4.3 17 Enteritis due to infection direct mucosal damage Small intestine 0 0 １ 1 1 Absent 18 F 1.0 1.7 3.8 11 Enteritis due to infection direct mucosal damage Small intestine 0 0 ２ 2 1 Absent F; Female, M; male. *Images were classified into dynamic, 2 h, 4 h, 6 h, and 24 h based on the timing of acquisition. For each timing, the intensity of tracer uptake in the intestinal tract was graded as follows: 3, marked uptake equal to or greater than liver level; 2, moderate uptake less than liver and greater than kidney levels; 1, mild uptake less than kidney level; and 0, negative uptake. **indicates that images were not obtained at this timing due to patient conditions or imaging result obtained before timing. Scintigraphy The dynamic phase was obtained for all patients during scintigraphy. However, images obtained at 2 and 24 h for one patient were not obtained due to the condition of the patient. Three patients did not have images obtained at some of the timepoints due to evidence of PLE before the respective timing. One lacked images at 6 and 24 h; one lacked images at 24 h; and another lacked images at 4, 6, and 24 h. The main leakage points of PLE were the small intestine for 16 patients and the large intestine for 2 patients. Tracer movement to the distal large intestine was detected in 12 patients. The grades of severity for scintigraphy at 2, 4, 6, and 24 h were 0.8 ± 1.2 [range, 0–3], 1.3 ± 1.0 [range, 0–3], 1.8 ± 1.0 [range, 0–3], 2.0 ± 0.9 [range, 1–3], and 1.8 ± 1.0 [range, 1–3], respectively. Comparison of patient characteristics and scintigraphy-based severity Table 2 summarizes the comparison of the characteristics of the patients and scintigraphy severity for the two etiological groups PLE. Significant differences were observed in the fecal alpha-1-antitrypsin concentration and scintigraphy severity during the delayed and super-delayed phases (alpha-1-antitrypsin in patients with direct mucosal damage vs those with failed lymph drainage: 43.5 ± 29.6 [range, 11–115] vs. 208.7 ± 66.0 [range, 124–311], P < 0.001; severity in 6-h image for direct mucosal damage vs failed lymph drainage : 1.6 ± 0.8 [range, 1–3] vs. 2.6 ± 0.5 [range, 2–3], P = 0.031; severity in 24-h image for direct mucosal damage vs failed lymph drainage =: 1.2 ± 0.8 [range, 1–3] vs. 2.8 ± 0.4 [range, 2–3], P = 0.007). No significant differences were observed in sex, age, serum protein concentration, albumin concentration, location of the main leakage point, tracer movement into the distal large intestine, and scintigraphy-based severity obtained at other times. Table 2 Comparison of the severity of scintigraphy findings between patients’ characteristics and scintigraphy results Mechanism of PLE direct mucosal damage failed lymph drainage P 11 7 Sex female/male 8/3 1/6 0.050 Age 7.2 ± 8.2 [range, 0.3–25.5] 4.9 ± 3.2 [range, 1.2–10.7] 0.724 Total protein 5.2 ± 1.3 [range, 3.8–7.1] 4.4 ± 0.6 [range, 3.6–5.2] 0.285 Total albumin 2.7 ± 0.8 [range, 1.6–4.1] 2.4 ± 0.4 [range, 1.9–2.5] 0.425 Fecal alfa-1 antitrypsin 43.5 ± 29.6 [range, 11–115] 208.7 ± 66.0 [range, 124–311] 0.999 Severity of scintigraphy* − 1 h 0.5 ± 1.0 [range, 0–3] 0.6 ± 1.0 [range, 0–2] > 0.999 2 h 0.8 ± 1.2 [range, 0–3] 1.2 ± 1.0 [range, 0–2] 0.525 4 h 1.8 ± 0.8 [range, 1–3] 2.0 ± 1.0 [range, 0–3] 0.536 6 h 1.8 ± 0.9 [range, 1–3] 2.5 ± 0.5 [range, 2–3] 0.147 24 h 1.2 ± 0.8 [range, 1–3] 2.8 ± 0.4 [range, 2–3] 0.007 Movement of tracer into distal large intestine (present/absent) 7/4 6/1 0.316 *Images were classified into dynamic, 2 h, 4 h, 6 h, and 24 h based on obtaining timing. In each timing, the intensity of tracer uptake in the intestinal tract was classified into the following grades: 3, marked uptake as equal to or greater than the liver; 2, moderate uptake as less than the liver and greater than the kidney; 1, mild uptake as less than the kidney; and 0, negative uptake. Correlation between scintigraphy-based severity and laboratory data Table 3 summarizes the correlations between the scintigraphy-based severity and laboratory data. The fecal alpha-1-antitrypsin concentration had moderate positive correlations with scintigraphy-based severity at 6 h (r = 0.499, P = 0.049) and 24 h (r = 0.747, P = 0.002). The serum protein concentration had a significant negative correlation with scintigraphy-based severity at 6 h (r = -0.587, P = 0.017), but no significant correlations were observed at other time points. Albumin concentration did not also have a significant correlation with scintigraphy-based severity. Table 3 Associations between scintigraphy-based severity and laboratory findings Severity of scintigraphy in each timing* -1 h 2 h 4 h 6 h 24 h Age -0.132 (0.601) -0.239 (0.356) -0.039 (0.811) -0.077 (0.778) 0.026(0.929) Laboratory data Serum protein concentration -0.317 (0.199) -0.390 (0.122) -0.246 (0.341) -0.587 (0.017)** -0.256 (0.378) Serum albumin concentration -0.288 (0.363) -0.310 (0.226) -0.154 (0.556) -0.470 (0.066) -0.111 (0.705) Fecalα-1-antitrypsin concentration -0.195 (0.438) 0.155 (0.553) 0.254 (0.554) 0.499 (0.049)** 0.747 (0.002)** *Images were classified into dynamic, 2 h, 4 h, 6 h, and 24 h based on the timing of acquisition. For each timing, the intensity of tracer uptake in the intestinal tract was graded as follows: 3, marked uptake equal to or greater than liver level; 2, moderate uptake less than liver and greater than kidney levels; 1, mild uptake less than kidney level; and 0, negative uptake. ** indicates significant association between laboratory data and severity of scintigraphy findings DISCUSSION In our limited cohort, scintigraphy-based severity obtained at 24 h and fecal alpha-1 antitrypsin concentrations were higher for patients with PLE due to failed lymph drainage than for those with PLE due to direct mucosal damage. The scintigraphy-based severity obtained at 6 and 24 h tended to correlate with spot fecal alpha-1-antitrypsin concentration. Technetium-99m albumin scintigraphy provided information on the location of leakage and the severity of protein loss in the gastrointestinal tract. This information would be useful for managing patients with PLE. The failed lymph drainage mechanisms of PLE are classified into primary (intestinal lymphangiectasia due to defects intrinsic to the lymphatic system) and secondary (external obstruction to lymph vessels or cardiovascular disease that impairs lymphatic flow)[ 1 – 3 ]. All patients with PLE due to failed lymph drainage in our cohort had congenital heart disease with Fontan operation or right-sided hypertension [ 1 , 3 , 5 , 19 ]. These conditions impair lymphatic flow and extend to the entire intestine. Moreover, follow-up for such patients tends to be prolonged from birth, during which they are exposed to impaired lymphatic flow [ 5 , 20 , 21 ]. Therefore, these cases had severe scintigraphy results and fecal alpha-1 antitrypsin concentrations compared to those with mucosal damage that may be due to segmental lesions and are usually acquired conditions and not congenital conditions [ 4 , 6 , 7 , 22 – 24 ]. PLE is one of the most important complications in patients with Fontan operation due to its high mortality rate of 50%[ 25 ], and its severity may be associated with the scintigraphy-based severity. Takeda et al. reported three cases of PLE associated with fecal alpha-1 antitrypsin concentration and scintigraphy-based severity. Their images demonstrated the correspondence between the scintigraphy-based severity and concentration of fecal alpha-1 antitrypsin [ 14 ]. Halaby et al. reported that images obtained more than 2 h after the dynamic phase had higher tracer accumulation within the gastrointestinal tract [ 10 ]. These findings are consistent with our results. However, the findings of a few cases in our cohort did not match the severity based on laboratory data and scintigraphy results. Protein-losing enteropathy is characterized by nonselective depletion of all plasma proteins, and the condition of the patients is affected by the turnover rates of various types of proteins, such as albumin and immunoglobulin [ 2 , 3 ]. Technetium-99m albumin scintigraphy visualizes only the depletion of albumin, not all plasma protein [ 9 , 10 , 12 , 14 , 17 ]. This may explain the differences in our results. The timing of scintigraphy is important. The dynamic phase obtained within 1 h represents both intestinal perfusion and tracer leakage into the intestinal tract. Images obtained after 2 h indicate the amount of tracer in the intestinal tract, while those obtained at 6 and 24 h tend to help visualize its accumulation. The amount of leakage into the intestinal tract may be associated with protein loss and laboratory abnormalities. Fecal alpha-1-antitrypsin concentrations directly reflect protein leakage into the stool, whereas albumin and protein concentrations reflect various patient conditions, such as prolonged inflammation and malnutrition. Therefore, it was understandable to note a significant positive correlation only between fecal alpha-1-antitrypsin concentrations and severity of 24-h scintigraphy and not between serum albumin and protein concentrations. Only the negative correlation between 6-h scintigraphy and serum protein concentration was not explained. Bhatgar et al. reported that scintigraphy-based severity was higher for patients with direct mucosal damage than for those with failed lymph drainage [ 8 ]. Three patients with failed lymph drainage were included in this study: one had congenital heart disease, and two had lymphangiectasia without cardiac anomalies. These results suggest that patients with failed lymph drainage and localized lesions may not have severe scintigraphy findings. The movement of the tracer into the distal large intestine is an important finding for the diagnosis of PLE via technetium-99m albumin scintigraphy. Tracer movement is usually easily detected in cases with marked tracer uptake in the intestine. Scintigraphy was useful in our study, but it had some limitations. First, we included only 18 patients with PLE. We did not include patients with congenital intestinal lymphangiectasia. We only included patients with congenital heart disease in the failed lymph drainage group. Studies involving more patients with various underlying diseases are needed. Second, we used spot fecal alpha-1-antitrypsin tests instead of calculating its clearance. It was difficult to correct the total fecal alpha-1-antitrypsin concentrations in our patients at the children's hospital for one day. Third, we did not include patients who had not undergone fecal alpha-1-antitrypsin testing or had negative results. Fecal alpha-1-antitrypsin testing is an important screening examination for PLE [ 2 , 3 ]. However, Chau et al reported the diagnostic performance of scintigraphy for PLE was superior to that of fecal alpha-1-antitrypthin concentration [ 16 ]. Therefore, we could not evaluate the scintigraphy-based severity for patients with negative fecal alpha-1-antitrypsin results. Further studies should include these patients. Declarations Funding None. Acknowledgement We would like to thank Editage [ http://www.editage.com ] for editing and reviewing this manuscript for English language References Braamskamp MJ, Dolman KM, Tabbers MM. Clinical practice. Protein-losing enteropathy in children. Eur J Pediatr. 2010;169:1179-85. Umar SB, DiBaise JK. Protein-losing enteropathy: case illustrations and clinical review. Am J Gastroenterol. 2010;105:43-9; quiz 50. Ozen A, Lenardo MJ. Protein-Losing Enteropathy. N Engl J Med. 2023;389:733-48. Wang YF, Tseng KC, Chiu JS, et al. 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Pediatrics. 2003;112:e242-7. Ishigami S, King G, Buratto E, et al. Outcomes of extracardiac Fontan operation: A single institution experience with 398 patients. J Thorac Cardiovasc Surg. 2025;169:400-10.e7. Mauro A, Giani T, Di Mari C, et al. Gastrointestinal Involvement in Children with Systemic Lupus Erythematosus. Children (Basel). 2023;10. van Hoeve K, De Keukelaere M, De Hertogh G, et al. Child with protein losing enteropathy as presentation of collagenous duodenitis and eosinophilic gastroenteritis. Acta Gastroenterol Belg. 2023;86:363-6. Chehade M, Magid MS, Mofidi S, et al. Allergic eosinophilic gastroenteritis with protein-losing enteropathy: intestinal pathology, clinical course, and long-term follow-up. J Pediatr Gastroenterol Nutr. 2006;42:516-21. Mertens L, Hagler DJ, Sauer U, et al. Protein-losing enteropathy after the Fontan operation: an international multicenter study. PLE study group. J Thorac Cardiovasc Surg. 1998;115:1063-73. Cite Share Download PDF Status: Published Journal Publication published 22 Sep, 2025 Read the published version in Annals of Nuclear Medicine → Version 1 posted Reviewers agreed at journal 14 Jul, 2025 Reviewers invited by journal 14 Jul, 2025 Editor assigned by journal 10 Jul, 2025 First submitted to journal 09 Jul, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7088989","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":484887936,"identity":"33f637aa-d8ad-4092-8c88-f9397ad96418","order_by":0,"name":"Takahiro Hosokawa","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA8klEQVRIiWNgGAWjYNCCAoYEBvbGBoYKEIeHgcGAsBYDoBaegw0MZ0jTIpHAANeCF8jPbj4m+cXAJo9f8nHbgwMVdXL8PAcYigvwmX/nWJq0jEFaseTsxHaDA2cOG0v2NjAYz8CnRSLH7LaEweHEDbcT26Q/th1I3HCegcEYn+PkZ0C17L95sE3iYFtd/X5CWhhu5Jjd/ACyRYIRpIU5wYC3Ab8Wgxtp6b8ZgH6ROJPYJgH0i+GMMwcb8PpFfkbyYcMfFcAQaz/+TAIYYvL8PcnHjPGFGAgwozmDsc2YgA4Gxh/oZjwmpGUUjIJRMApGFAAAom5Rad3Ju48AAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0001-9523-4077","institution":"Saitama Children's Medical Center","correspondingAuthor":true,"prefix":"","firstName":"Takahiro","middleName":"","lastName":"Hosokawa","suffix":""},{"id":484887937,"identity":"e114bd37-44f3-4e66-9115-01ffa1877225","order_by":1,"name":"Mayuki Uchiyama","email":"","orcid":"","institution":"jikei univercity","correspondingAuthor":false,"prefix":"","firstName":"Mayuki","middleName":"","lastName":"Uchiyama","suffix":""},{"id":484887938,"identity":"1f9bf1bb-e081-4e35-92a0-9d9e0d83cf4e","order_by":2,"name":"Sakie Namba","email":"","orcid":"","institution":"saitama children's medical center","correspondingAuthor":false,"prefix":"","firstName":"Sakie","middleName":"","lastName":"Namba","suffix":""},{"id":484887939,"identity":"40c33f5b-444c-4e81-b52e-c88630122e1b","order_by":3,"name":"Yutaka Tanami","email":"","orcid":"","institution":"saitama children's medical center","correspondingAuthor":false,"prefix":"","firstName":"Yutaka","middleName":"","lastName":"Tanami","suffix":""},{"id":484887940,"identity":"7618dbed-d63a-4592-9a02-2251bc50bc87","order_by":4,"name":"yumiko Sato","email":"","orcid":"","institution":"saitama children's medical center","correspondingAuthor":false,"prefix":"","firstName":"yumiko","middleName":"","lastName":"Sato","suffix":""},{"id":484887941,"identity":"40781c53-2a15-4d13-aa73-5db043affa20","order_by":5,"name":"Yasuharu Wakabayashi","email":"","orcid":"","institution":"Faculty of Health Science","correspondingAuthor":false,"prefix":"","firstName":"Yasuharu","middleName":"","lastName":"Wakabayashi","suffix":""},{"id":484887942,"identity":"d5ba945e-2067-4824-a272-d32198a6d353","order_by":6,"name":"Eiji Oguma","email":"","orcid":"","institution":"saitama children's medical center","correspondingAuthor":false,"prefix":"","firstName":"Eiji","middleName":"","lastName":"Oguma","suffix":""}],"badges":[],"createdAt":"2025-07-10 05:07:46","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7088989/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7088989/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s12149-025-02109-5","type":"published","date":"2025-09-22T15:57:14+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":87036187,"identity":"97a0cd13-9112-4189-b188-3afc932d1b50","added_by":"auto","created_at":"2025-07-18 13:19:46","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":3086919,"visible":true,"origin":"","legend":"\u003cp\u003eCase 1. Technetium-99m albumin scintigraphy in a 7.5-year-old male patient after the Fontan operation (failed lymph drainage). Serum albumin, total protein, and fecal alpha-1 antitrypsin concentrations were 2.6 g/dL, 4.8 g/dL, and 311 mg/dL, respectively.\u003c/p\u003e\n\u003cp\u003ea. Anterior image obtained 1 h after injection (dynamic phase) shows non-focal intestinal accumulation. The uptake grade is 0 (negative).\u003c/p\u003e\n\u003cp\u003eb. Anterior image obtained 2 h after injection shows small intestinal activity (arrow). The severity of this uptake is less than that of the liver but greater than that of the kidney. Therefore, the small intestine is the main leakage point, and the grade is 2 as marked.\u003c/p\u003e\n\u003cp\u003ec. Anterior image obtained 4 h after injection shows small intestinal activity (arrow). The severity of this uptake is equal to or greater than that of the liver.\u003c/p\u003e\n\u003cp\u003ed. Anterior image obtained 6 h after injection shows small intestinal activity, which has moved from the early phase (arrow). The severity of this uptake is equal to or greater than that of the liver.\u003c/p\u003e\n\u003cp\u003ee. Anterior image obtained 24 h after injection shows greater tracer uptake than that in the liver (arrow). Therefore, grade is 3 as marked. The tracer has moved into the distal large intestine, including the transverse colon (vacant arrowhead) and sigmoid colon (solid arrowhead). Tracer movement into the large intestine is present.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7088989/v1/d1e8f0afde6d797796d42db9.png"},{"id":87034938,"identity":"98c214ff-ca75-4d5f-b874-fecdf3751f41","added_by":"auto","created_at":"2025-07-18 13:11:46","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":3044289,"visible":true,"origin":"","legend":"\u003cp\u003eCase 11. The technetium-99m albumin scintigraphy findings for a 16.2-year-old female patient with enteritis (direct mucosal damage) are provided in Fig. 2. The serum albumin, total protein, and fecal alpha-1 antitrypsin concentrations were 3.5 g/dl, 5.6 g/dl, and 56 mg/dl, respectively.\u003c/p\u003e\n\u003cp\u003ea. Anterior image obtained 1 h after injection (dynamic phase) shows no abnormal focal intestinal accumulation. The severity of tracer accumulation is negative, as grade 0.\u003c/p\u003e\n\u003cp\u003eb. Anterior image obtained 2 h after injection shows no abnormal focal intestinal accumulation, and the severity of tracer accumulation is grade 0.\u003c/p\u003e\n\u003cp\u003ec. Anterior image obtained 4 h after injection shows abnormal focal intestinal accumulation in the transverse colon (arrow). The severity of tracer accumulation is worse than that of the kidney but less than that of the liver. Grade of uptake is 2 as moderate. The main leakage point is the large intestine.\u003c/p\u003e\n\u003cp\u003ed. Anterior image taken 6 h after injection shows abnormal focal intestinal accumulation at the transverse colon (arrowhead). The severity of tracer accumulation is greater than that of the kidney but less than that of the liver. It is graded 2 as mild.\u003c/p\u003e\n\u003cp\u003ee. Anterior image obtained 24 h after injection shows abnormal focal intestinal accumulation in the descending colon (arrowhead). The severity of tracer accumulation is less than that of the kidney. Grade is 1 as mild. Tracer movement into the distal large intestine is present.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7088989/v1/c3190f0b0d9d010801867f3b.png"},{"id":87034925,"identity":"f39b45dd-5d2a-42cd-b5dd-07fd05d6d490","added_by":"auto","created_at":"2025-07-18 13:11:45","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":3981067,"visible":true,"origin":"","legend":"\u003cp\u003eCase 15. Technetium-99m albumin scintigraphy in a 2.6-year-old female patient with enteritis (direct mucosal damage). Serum albumin, total protein, and fecal alpha-1 antitrypsin concentrations were 3.3 g/dL, 7.0 g/dL, and 21 mg/dL, respectively.\u003c/p\u003e\n\u003cp\u003ea. Anterior image obtained 1 h after injection (dynamic phase) shows no abnormal focal intestinal accumulation. The severity of tracer accumulation is negative, and the grade of uptake is 0.\u003c/p\u003e\n\u003cp\u003eb. Anterior image obtained 2 h after injection shows no abnormal focal intestinal accumulation. The severity of tracer accumulation is negative and grade 0.\u003c/p\u003e\n\u003cp\u003ec. Anterior image obtained 4 h after injection shows abnormal focal intestinal accumulation in the left lower abdomen (arrow). The tracer activity in this area is less than that of the kidney. The severity of tracer accumulation is grade 1 as mild.\u003c/p\u003e\n\u003cp\u003ed. Anterior image obtained 6 h after injection shows small intestinal activity. The severity of this uptake is less than that of the kidney (arrow). Therefore, the small intestine is the main leakage point and is classified as grade 1 (mild).\u003c/p\u003e\n\u003cp\u003ee. Anterior image obtained 24 h after injection shows tracer accumulation in the small intestine but not in the distal large intestine (arrow). Therefore, the movement of tracer into the distal large intestine is absent. This uptake is less than that of the kidney and grade is 1 as mild.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-7088989/v1/d3b56ce1ed69dd6b5e162a93.png"},{"id":92430444,"identity":"682e1d3a-9235-45ef-ad6d-343e1597352a","added_by":"auto","created_at":"2025-09-29 16:04:14","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":10805493,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7088989/v1/730f675f-ec21-43bd-9b5d-2e3757780baf.pdf"}],"financialInterests":"","formattedTitle":"Association between technetium-99m albumin scintigraphy-based severity of protein-losing enteropathy and patient characteristics and laboratory data","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eProtein-losing enteropathy (PLE) is rare condition characterized by protein loss into the gastrointestinal tract [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. The two principal underlying pathophysiological mechanisms are direct mucosal damage (either erosive or nonerosive) and failed lymph drainage, causing backflow through the epithelium into the lumen [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Patient outcomes and treatment vary based on these mechanisms [\u003cspan additionalcitationids=\"CR5 CR6\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. In addition, the severity of laboratory findings of the patients is associated with PLE recurrence after treatment [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe fecal alpha-1-antitrypsin concentration and technetium-99m albumin scintigraphy findings are important for diagnosing this PLE [\u003cspan additionalcitationids=\"CR9 CR10 CR11 CR12 CR13\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Fecal alpha-1-antitrypsin is usually the first examination for patients with suspected PLE, and it can predict the amount of protein lost into the intestine [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Technetium-99m albumin scintigraphy is also useful for diagnosing PLE, as it helps visualize the tracer in the gastrointestinal tract and detect the leakage point [\u003cspan additionalcitationids=\"CR9\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. However, systematic studies on the associations of the severity of patient conditions and laboratory data are lacking. Furthermore, few studies have discussed the severity of scintigraphy findings [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe purpose of this study was to demonstrate the differences in Technetium-99m albumin scintigraphy findings for PLE cases secondary to direct mucosal damage and failed lymph drainage. The study also aimed to describe the association between the scintigraphy-based severity of PLE and laboratory data of patients.\u003c/p\u003e"},{"header":"MATERIAL AND METHODS","content":"\u003cp\u003e\u003cb\u003eEthical considerations\u003c/b\u003e\u003c/p\u003e\u003cp\u003e This retrospective study was conducted in accordance with the principles of the Declaration of Helsinki. The ethics committee of our institution approved this study and waived the requirement for informed consent due to its retrospective design.\u003c/p\u003e\u003cp\u003e\u003cb\u003eStudy population\u003c/b\u003e\u003c/p\u003e\u003cp\u003eWe reviewed the medical database of our hospital and included patients with suspected PLE who underwent Technetium-99m albumin scintigraphy between April 2000 and May 2025. Twenty patients were enrolled in this study. Only the results of the first examination were evaluated for patients who underwent this examination multiple times.\u003c/p\u003e\u003cp\u003eThe exclusion criteria were as follows: unreviewed medical records (n\u0026thinsp;=\u0026thinsp;2).\u003c/p\u003e\u003cp\u003e\u003cb\u003ePatient data\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eSuspected PLE\u003c/b\u003e\u003c/p\u003e\u003cp\u003ePLE has various symptoms, including hypoproteinemia, edema, nutritional deficiency, and recurrent infection [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] The fecal alpha-1-antitrypsin concentrations were determined for these cases, and a spot value greater than 10 mg/dl indicated PLE positivity or warranted its suspicion. The clearance was better for evaluating the amount of protein lost. However, it was difficult to calculate the protein loss for patients in our hospital using the amount of feces in one day.\u003c/p\u003e\u003cp\u003e\u003cem\u003ePatient characteristics and laboratory data\u003c/em\u003e\u003c/p\u003e\u003cp\u003eFollowing data were recorded; sex, age of scintigraphy examination, underlying disease associated with PLE and spot value of alfa-1 antitrypsin. In addition, serum albumin and serum protein levels obtained on the same day of scintigraphy examination were recorded.\u003c/p\u003e\u003cp\u003e\u003cem\u003ePatient classification\u003c/em\u003e\u003c/p\u003e\u003cp\u003ePatients were classified into two groups based on the mechanism: direct mucosal damage or failed lymph drainage. Direct mucosal damage includes inflammatory and ulcerative diseases, infections, malignancy, hypertrophic gastropathies, eosinophilic gastroenteropathies, vasculitic disorders. Failed lymph drainage includes primary lymphangiectasia and secondary lymphangiectasia such as obstructive or elevated lymph pressure caused by congenital heart disease or syndrome [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e\u003cp\u003e\u003cem\u003eTechnetium-99m albumin scintigraphy\u003c/em\u003e\u003c/p\u003e\u003cp\u003eEquipment and examination protocol: Technetium-99m Albumin scintigraphy was performed in patients with suspected PLE, who had symptoms such as diarrhea, generalized edema, low serum protein, low serum albumin, or/and high fecal α-1-antitrypsin. Doses of 50 MBq of Technetium-99m labeled human serum albumin-DTPA (99mTc-HSAD) were determined based on the Japanese Society of Nuclear Medicine guidelines (administration dose range 73.1\u0026ndash;740 MBq)[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. A gamma camera (Siemens Symbia E or T16; Siemens Medical Systems Inc., Hoffmann Estates, IL, USA) equipped with a fan beam collimator was used. A 60-min anterior dynamic sequence captured the dynamic phase (Figs.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e3\u003c/span\u003e, 4, 5), followed by the acquisition of static anterior, posterior, and both right and left lateral images at 2, 4, 6, or 24 h post-injection. Previous images could not be obtained in some cases due to those general conditions. For cases with difficulty assessing bowel activity in static images, single-photon emission computerized tomography (SPECT) scans were obtained. The dynamic sequence was obtained with a 64 \u0026times; 64 matrix size and at sampling times of 30 s. All static images were obtained with a 512 \u0026times; 512 matrix size and at varying sampling times (300 s at 3 h, 300 s at 6 h, and 900 s at 24 h).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eEvaluation of scintigraphy results: The examination results were evaluated based on previous studies [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. The timing of image evaluations varied across studies, which may lead to confusion when comparing the studies [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Therefore, we classified the timing of imaging evaluations based on the time of acquisition as follows: dynamic images acquired within the first hour; images obtained at 2 h; images obtained at 4 h; images obtained at 6 h; and images obtained at 24 h after the commencement of the examination. The intensity of tracer uptake in the intestinal tract was graded as follows: 3, marked uptake equal to or greater than that in the liver (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003e); 2, moderate uptake less than that in the liver and greater than that in the kidney (Figs.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003e, \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e2\u003c/span\u003e); 1, mild uptake less than that in the kidney (Figs.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e2\u003c/span\u003e, \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e3\u003c/span\u003e); and 0, negative uptake (Figs.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e3\u003c/span\u003e)[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]). For cases with greater uptake in the kidney than in the liver, marked uptake was defined as equal to or greater than that in the kidney, moderate uptake as less than that in the kidney and greater than that in the liver, and mild uptake as less than that in the liver. The main leakage points of PLE were classified into the small intestine (Figs.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003e, \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e3\u003c/span\u003e) and large intestine (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The presence (Figs.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003e, \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e2\u003c/span\u003e) or absence (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e3\u003c/span\u003e) of tracer movement to the distal large intestine was evaluated.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eReview process: Two pediatric radiologists with 25 and 10 years of clinical experience in pediatric nuclear medicine independently reviewed all images of technetium-99m albumin scintigraphy using a 1600 \u0026times; 1200 picture archiving and communication system (PACS; GE Healthcare). Discrepancies in interpretation between the radiologists were resolved by consensus.\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStatistical analysis\u003c/h2\u003e\u003cp\u003eThe data are presented as the mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation. Statistical significance was set at P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 (two-sided) for all tests. All analyses were performed using IBM SPSS Statistics for Windows version 24 (IBM Corp., Armonk, NY, USA).\u003c/p\u003e\u003cp\u003eThe characteristics of the patients with PLE caused by direct mucosal damage and those with PLE caused failed lymph drainage, including sex, age, and scintigraphy findings such as main leakage point of PLE and presence or absence of tracer movement to distal large intestine, were compared using Fisher\u0026rsquo;s exact test and the Mann-Whitney U test. The uptake intensities for each timing were compared for the two groups using the Mann-Whitney U test.\u003c/p\u003e\u003cp\u003eThe associations between those grades and age and serum albumin, serum protein, and fecal alpha-1-antitrypsin concentrations were evaluated using Pearson correlation coefficients.\u003c/p\u003e\u003c/div\u003e"},{"header":"RESULTS","content":"\u003cp\u003e\u003cb\u003ePatient characteristics\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThe patient characteristics are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Eighteen patients were enrolled in this study. Of these, 11 had direct mucosal damage, and seven had failed lymph drainage. The underlying diseases or final diagnoses of the 11 patients with direct mucosal damage were enteritis due to infection by unknown pathogens in eight patients, cytomegalovirus infection in one patient, and systemic lupus erythematosus or juvenile idiopathic arthritis in one patient each. Of the seven patients with failed lymph drainage, five had undergone the Fontan operation, and two had right-sided hypertension due to congenital heart disease before the Fontan operation. Nine patients were male and nine were female. Their average age was 6.3\u0026thinsp;\u0026plusmn;\u0026thinsp;6.7 [range, 0.3\u0026ndash;25.5] years. Their average serum total protein, serum albumin, and fecal alpha-1-antitrypsin concentrations were 4.9\u0026thinsp;\u0026plusmn;\u0026thinsp;1.1 [range, 3.5\u0026ndash;7.1] g/dl, 2.6\u0026thinsp;\u0026plusmn;\u0026thinsp;0.7 [range, 1.6\u0026ndash;4.1] g/dl, and 107.8\u0026thinsp;\u0026plusmn;\u0026thinsp;94.4 [range, 11\u0026ndash;311] mg/dl, respectively.\u003c/p\u003e\u003cp\u003eTable 1. Patient characteristics\u003c/p\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"1021\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 28px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 38px;\"\u003e\n \u003cp\u003esex\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 47px;\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003cp\u003e(years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 57px;\"\u003e\n \u003cp\u003eSerum Albumin\u003c/p\u003e\n \u003cp\u003e(g/dl)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 57px;\"\u003e\n \u003cp\u003eSerum protein\u003c/p\u003e\n \u003cp\u003e(g/dl)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 76px;\"\u003e\n \u003cp\u003eFecal alfa-1-antitrypsin\u003c/p\u003e\n \u003cp\u003e(mg/dl)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 180px;\"\u003e\n \u003cp\u003eUnderlying disease/diagnosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 113px;\"\u003e\n \u003cp\u003eMechanism of PLE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 94px;\"\u003e\n \u003cp\u003eLeakage point\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" style=\"width: 198px;\"\u003e\n \u003cp\u003eGrade of tracer intensity in each timing*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 95px;\"\u003e\n \u003cp\u003eTracer movement into distal large intestine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 38px;\"\u003e\n \u003cp\u003eFig\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003e-1 h\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40px;\"\u003e\n \u003cp\u003e2 h\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e4 h\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 37px;\"\u003e\n \u003cp\u003e6 h\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003e24 h\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003eM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e7.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e2.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e4.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e311\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 180px;\"\u003e\n \u003cp\u003eAfter Fontan operation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003efailed lymph drainage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003eSmall intestine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 37px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003ePresent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003eFig 1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003eM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e1.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e5.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e269\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 180px;\"\u003e\n \u003cp\u003eRight side hypertension before Fontan operation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003efailed lymph drainage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003eSmall intestine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 37px;\"\u003e\n \u003cp\u003e**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003e**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003ePresent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003eM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e10.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e2.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e4.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e220\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 180px;\"\u003e\n \u003cp\u003eAfter Fontan operation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003efailed lymph drainage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003eSmall intestine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40px;\"\u003e\n \u003cp\u003e０\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 37px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003ePresent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003eF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e3.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e2.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e3.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e210\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 180px;\"\u003e\n \u003cp\u003eAfter Fontan operation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003efailed lymph drainage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003eSmall intestine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e０\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 37px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003ePresent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003eM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e4.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e2.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e4.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e182\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 180px;\"\u003e\n \u003cp\u003eRight side hypertension before Fontan operation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003efailed lymph drainage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003eLarge intestine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40px;\"\u003e\n \u003cp\u003e**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e２\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 37px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003e**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003eAbsent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003eM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e3.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e1.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e3.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e145\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 180px;\"\u003e\n \u003cp\u003eAfter Fontan operation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003efailed lymph drainage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003eSmall intestine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e２\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 37px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003ePresent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003eM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e4.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e2.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e4.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e124\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 180px;\"\u003e\n \u003cp\u003eAfter Fontan operation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003efailed lymph drainage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003eSmall intestine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40px;\"\u003e\n \u003cp\u003e２\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e３\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 37px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003ePresent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003eM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e3.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e1.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e3.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e115\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 180px;\"\u003e\n \u003cp\u003eEnteritis due to infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003edirect mucosal damage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003eSmall intestine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 37px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003eAbsent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003eM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e3.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e3.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e6.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 180px;\"\u003e\n \u003cp\u003eEnteritis due to infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003edirect mucosal damage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003eSmall intestine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 37px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003ePresent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003eF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e25.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e2.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e4.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 180px;\"\u003e\n \u003cp\u003eEnteritis due to infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003edirect mucosal damage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003eSmall intestine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e１\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 37px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003ePresent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003eF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e16.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e3.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e5.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 180px;\"\u003e\n \u003cp\u003eJuvenile idiopathic arthritis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003edirect mucosal damage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003eLarge intestine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40px;\"\u003e\n \u003cp\u003e０\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e２\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 37px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003ePresent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003eFig 2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003eF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e14.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e2.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e4.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 180px;\"\u003e\n \u003cp\u003eSystematic lupus arthropathy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003edirect mucosal damage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003eSmall intestine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e３\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 37px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003ePresent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003eF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e0.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e2.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 180px;\"\u003e\n \u003cp\u003eCytomegalovirus infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003edirect mucosal damage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003eSmall intestine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40px;\"\u003e\n \u003cp\u003e３\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e３\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 37px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003e**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003ePresent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003eF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e9.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e4.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e7.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 180px;\"\u003e\n \u003cp\u003eEnteritis due to infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003edirect mucosal damage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003eSmall intestine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40px;\"\u003e\n \u003cp\u003e０\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e１\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 37px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003ePresent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003eF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e2.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e3.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 180px;\"\u003e\n \u003cp\u003eEnteritis due to infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003edirect mucosal damage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003eSmall intestine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e１\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 37px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003eAbsent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003eFig 3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003eM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e2.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e3.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 180px;\"\u003e\n \u003cp\u003eEnteritis due to infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003edirect mucosal damage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003eSmall intestine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 37px;\"\u003e\n \u003cp\u003e**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003e**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003ePresent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003eF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e0.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e2.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e4.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 180px;\"\u003e\n \u003cp\u003eEnteritis due to infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003edirect mucosal damage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003eSmall intestine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e１\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 37px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003eAbsent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003eF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e1.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e3.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 180px;\"\u003e\n \u003cp\u003eEnteritis due to infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003edirect mucosal damage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003eSmall intestine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e２\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 37px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003eAbsent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eF; Female, M; male.\u003c/p\u003e\n\u003cp\u003e*Images were classified into dynamic, 2 h, 4 h, 6 h, and 24 h based on the timing of acquisition. For each timing, the intensity of tracer uptake in the intestinal tract was graded as follows: 3, marked uptake equal to or greater than liver level; 2, moderate uptake less than liver and greater than kidney levels; 1, mild uptake less than kidney level; and 0, negative uptake.\u003c/p\u003e\n\u003cp\u003e**indicates that images were not obtained at this timing due to patient conditions or imaging result obtained before timing. \u0026nbsp;\u003c/p\u003e\u003cp\u003e\u003cb\u003eScintigraphy\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThe dynamic phase was obtained for all patients during scintigraphy. However, images obtained at 2 and 24 h for one patient were not obtained due to the condition of the patient. Three patients did not have images obtained at some of the timepoints due to evidence of PLE before the respective timing. One lacked images at 6 and 24 h; one lacked images at 24 h; and another lacked images at 4, 6, and 24 h.\u003c/p\u003e\u003cp\u003eThe main leakage points of PLE were the small intestine for 16 patients and the large intestine for 2 patients. Tracer movement to the distal large intestine was detected in 12 patients.\u003c/p\u003e\u003cp\u003eThe grades of severity for scintigraphy at 2, 4, 6, and 24 h were 0.8\u0026thinsp;\u0026plusmn;\u0026thinsp;1.2 [range, 0\u0026ndash;3], 1.3\u0026thinsp;\u0026plusmn;\u0026thinsp;1.0 [range, 0\u0026ndash;3], 1.8\u0026thinsp;\u0026plusmn;\u0026thinsp;1.0 [range, 0\u0026ndash;3], 2.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.9 [range, 1\u0026ndash;3], and 1.8\u0026thinsp;\u0026plusmn;\u0026thinsp;1.0 [range, 1\u0026ndash;3], respectively.\u003c/p\u003e\u003cp\u003e\u003cb\u003eComparison of patient characteristics and scintigraphy-based severity\u003c/b\u003e\u003c/p\u003e\u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e summarizes the comparison of the characteristics of the patients and scintigraphy severity for the two etiological groups PLE. Significant differences were observed in the fecal alpha-1-antitrypsin concentration and scintigraphy severity during the delayed and super-delayed phases (alpha-1-antitrypsin in patients with direct mucosal damage vs those with failed lymph drainage: 43.5\u0026thinsp;\u0026plusmn;\u0026thinsp;29.6 [range, 11\u0026ndash;115] vs. 208.7\u0026thinsp;\u0026plusmn;\u0026thinsp;66.0 [range, 124\u0026ndash;311], P\u0026thinsp;\u0026lt;\u0026thinsp;0.001; severity in 6-h image for direct mucosal damage vs failed lymph drainage : 1.6\u0026thinsp;\u0026plusmn;\u0026thinsp;0.8 [range, 1\u0026ndash;3] vs. 2.6\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5 [range, 2\u0026ndash;3], P\u0026thinsp;=\u0026thinsp;0.031; severity in 24-h image for direct mucosal damage vs failed lymph drainage =: 1.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.8 [range, 1\u0026ndash;3] vs. 2.8\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4 [range, 2\u0026ndash;3], P\u0026thinsp;=\u0026thinsp;0.007). No significant differences were observed in sex, age, serum protein concentration, albumin concentration, location of the main leakage point, tracer movement into the distal large intestine, and scintigraphy-based severity obtained at other times.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eComparison of the severity of scintigraphy findings between patients\u0026rsquo; characteristics and scintigraphy results\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\u003e\u003cp\u003eMechanism of PLE\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003edirect mucosal damage\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003efailed lymph drainage\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eP\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eSex female/male\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8/3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1/6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.050\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eAge\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7.2\u0026thinsp;\u0026plusmn;\u0026thinsp;8.2 [range, 0.3\u0026ndash;25.5]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4.9\u0026thinsp;\u0026plusmn;\u0026thinsp;3.2 [range, 1.2\u0026ndash;10.7]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.724\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eTotal protein\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1.3 [range, 3.8\u0026ndash;7.1]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6 [range, 3.6\u0026ndash;5.2]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.285\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eTotal albumin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.8 [range, 1.6\u0026ndash;4.1]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4 [range, 1.9\u0026ndash;2.5]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.425\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eFecal alfa-1 antitrypsin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e43.5\u0026thinsp;\u0026plusmn;\u0026thinsp;29.6 [range, 11\u0026ndash;115]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e208.7\u0026thinsp;\u0026plusmn;\u0026thinsp;66.0 [range, 124\u0026ndash;311]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e\u003cp\u003eTechnetium-99m labeled human serum albumin-DTPA\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eMain location of leakage point (small intestine/large intestine)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10/1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6/1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026gt;\u0026thinsp;0.999\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"4\" rowspan=\"5\"\u003e\u003cp\u003eSeverity of scintigraphy*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026minus;\u0026thinsp;1 h\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.5\u0026thinsp;\u0026plusmn;\u0026thinsp;1.0 [range, 0\u0026ndash;3]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.0 [range, 0\u0026ndash;2]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026gt;\u0026thinsp;0.999\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 h\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.8\u0026thinsp;\u0026plusmn;\u0026thinsp;1.2 [range, 0\u0026ndash;3]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1.0 [range, 0\u0026ndash;2]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.525\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4 h\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.8\u0026thinsp;\u0026plusmn;\u0026thinsp;0.8 [range, 1\u0026ndash;3]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.0\u0026thinsp;\u0026plusmn;\u0026thinsp;1.0 [range, 0\u0026ndash;3]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.536\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6 h\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.8\u0026thinsp;\u0026plusmn;\u0026thinsp;0.9 [range, 1\u0026ndash;3]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5 [range, 2\u0026ndash;3]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.147\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e24 h\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.8 [range, 1\u0026ndash;3]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.8\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4 [range, 2\u0026ndash;3]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.007\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eMovement of tracer into distal large intestine (present/absent)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7/4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6/1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.316\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003e*Images were classified into dynamic, 2 h, 4 h, 6 h, and 24 h based on obtaining timing. In each timing, the intensity of tracer uptake in the intestinal tract was classified into the following grades: 3, marked uptake as equal to or greater than the liver; 2, moderate uptake as less than the liver and greater than the kidney; 1, mild uptake as less than the kidney; and 0, negative uptake.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eCorrelation between scintigraphy-based severity and laboratory data\u003c/b\u003e\u003c/p\u003e\u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e summarizes the correlations between the scintigraphy-based severity and laboratory data. The fecal alpha-1-antitrypsin concentration had moderate positive correlations with scintigraphy-based severity at 6 h (r\u0026thinsp;=\u0026thinsp;0.499, P\u0026thinsp;=\u0026thinsp;0.049) and 24 h (r\u0026thinsp;=\u0026thinsp;0.747, P\u0026thinsp;=\u0026thinsp;0.002). The serum protein concentration had a significant negative correlation with scintigraphy-based severity at 6 h (r = -0.587, P\u0026thinsp;=\u0026thinsp;0.017), but no significant correlations were observed at other time points. Albumin concentration did not also have a significant correlation with scintigraphy-based severity.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eAssociations between scintigraphy-based severity and laboratory findings\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"7\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colspan=\"2\" morerows=\"1\" nameend=\"c2\" namest=\"c1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colspan=\"5\" nameend=\"c7\" namest=\"c3\"\u003e\u003cp\u003eSeverity of scintigraphy in each timing*\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-1 h\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2 h\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003e4 h\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003e6 h\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003e24 h\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eAge\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-0.132 (0.601)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-0.239 (0.356)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-0.039 (0.811)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-0.077 (0.778)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.026(0.929)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003eLaboratory data\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSerum protein concentration\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-0.317 (0.199)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-0.390 (0.122)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-0.246 (0.341)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-0.587 (0.017)**\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e-0.256 (0.378)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSerum albumin concentration\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-0.288 (0.363)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-0.310 (0.226)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-0.154 (0.556)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-0.470 (0.066)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e-0.111 (0.705)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eFecalα-1-antitrypsin concentration\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-0.195 (0.438)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.155 (0.553)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.254 (0.554)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.499 (0.049)**\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.747 (0.002)**\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"7\"\u003e*Images were classified into dynamic, 2 h, 4 h, 6 h, and 24 h based on the timing of acquisition. For each timing, the intensity of tracer uptake in the intestinal tract was graded as follows: 3, marked uptake equal to or greater than liver level; 2, moderate uptake less than liver and greater than kidney levels; 1, mild uptake less than kidney level; and 0, negative uptake.\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"7\"\u003e** indicates significant association between laboratory data and severity of scintigraphy findings\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eIn our limited cohort, scintigraphy-based severity obtained at 24 h and fecal alpha-1 antitrypsin concentrations were higher for patients with PLE due to failed lymph drainage than for those with PLE due to direct mucosal damage. The scintigraphy-based severity obtained at 6 and 24 h tended to correlate with spot fecal alpha-1-antitrypsin concentration. Technetium-99m albumin scintigraphy provided information on the location of leakage and the severity of protein loss in the gastrointestinal tract. This information would be useful for managing patients with PLE.\u003c/p\u003e\u003cp\u003eThe failed lymph drainage mechanisms of PLE are classified into primary (intestinal lymphangiectasia due to defects intrinsic to the lymphatic system) and secondary (external obstruction to lymph vessels or cardiovascular disease that impairs lymphatic flow)[\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. All patients with PLE due to failed lymph drainage in our cohort had congenital heart disease with Fontan operation or right-sided hypertension [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. These conditions impair lymphatic flow and extend to the entire intestine. Moreover, follow-up for such patients tends to be prolonged from birth, during which they are exposed to impaired lymphatic flow [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Therefore, these cases had severe scintigraphy results and fecal alpha-1 antitrypsin concentrations compared to those with mucosal damage that may be due to segmental lesions and are usually acquired conditions and not congenital conditions [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan additionalcitationids=\"CR23\" citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. PLE is one of the most important complications in patients with Fontan operation due to its high mortality rate of 50%[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e], and its severity may be associated with the scintigraphy-based severity.\u003c/p\u003e\u003cp\u003eTakeda et al. reported three cases of PLE associated with fecal alpha-1 antitrypsin concentration and scintigraphy-based severity. Their images demonstrated the correspondence between the scintigraphy-based severity and concentration of fecal alpha-1 antitrypsin [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Halaby et al. reported that images obtained more than 2 h after the dynamic phase had higher tracer accumulation within the gastrointestinal tract [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. These findings are consistent with our results. However, the findings of a few cases in our cohort did not match the severity based on laboratory data and scintigraphy results. Protein-losing enteropathy is characterized by nonselective depletion of all plasma proteins, and the condition of the patients is affected by the turnover rates of various types of proteins, such as albumin and immunoglobulin [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Technetium-99m albumin scintigraphy visualizes only the depletion of albumin, not all plasma protein [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. This may explain the differences in our results.\u003c/p\u003e\u003cp\u003eThe timing of scintigraphy is important. The dynamic phase obtained within 1 h represents both intestinal perfusion and tracer leakage into the intestinal tract. Images obtained after 2 h indicate the amount of tracer in the intestinal tract, while those obtained at 6 and 24 h tend to help visualize its accumulation. The amount of leakage into the intestinal tract may be associated with protein loss and laboratory abnormalities. Fecal alpha-1-antitrypsin concentrations directly reflect protein leakage into the stool, whereas albumin and protein concentrations reflect various patient conditions, such as prolonged inflammation and malnutrition. Therefore, it was understandable to note a significant positive correlation only between fecal alpha-1-antitrypsin concentrations and severity of 24-h scintigraphy and not between serum albumin and protein concentrations. Only the negative correlation between 6-h scintigraphy and serum protein concentration was not explained.\u003c/p\u003e\u003cp\u003eBhatgar et al. reported that scintigraphy-based severity was higher for patients with direct mucosal damage than for those with failed lymph drainage [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Three patients with failed lymph drainage were included in this study: one had congenital heart disease, and two had lymphangiectasia without cardiac anomalies. These results suggest that patients with failed lymph drainage and localized lesions may not have severe scintigraphy findings.\u003c/p\u003e\u003cp\u003eThe movement of the tracer into the distal large intestine is an important finding for the diagnosis of PLE via technetium-99m albumin scintigraphy. Tracer movement is usually easily detected in cases with marked tracer uptake in the intestine.\u003c/p\u003e\u003cp\u003eScintigraphy was useful in our study, but it had some limitations. First, we included only 18 patients with PLE. We did not include patients with congenital intestinal lymphangiectasia. We only included patients with congenital heart disease in the failed lymph drainage group. Studies involving more patients with various underlying diseases are needed. Second, we used spot fecal alpha-1-antitrypsin tests instead of calculating its clearance. It was difficult to correct the total fecal alpha-1-antitrypsin concentrations in our patients at the children's hospital for one day. Third, we did not include patients who had not undergone fecal alpha-1-antitrypsin testing or had negative results. Fecal alpha-1-antitrypsin testing is an important screening examination for PLE [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. However, Chau et al reported the diagnostic performance of scintigraphy for PLE was superior to that of fecal alpha-1-antitrypthin concentration [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Therefore, we could not evaluate the scintigraphy-based severity for patients with negative fecal alpha-1-antitrypsin results. Further studies should include these patients.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eFunding\u003c/h2\u003e\u003cp\u003eNone.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eWe would like to thank Editage [\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://www.editage.com\u003c/span\u003e\u003cspan address=\"http://www.editage.com\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e] for editing and reviewing this manuscript for English language\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBraamskamp MJ, Dolman KM, Tabbers MM. Clinical practice. Protein-losing enteropathy in children. Eur J Pediatr. 2010;169:1179-85.\u003c/li\u003e\n\u003cli\u003eUmar SB, DiBaise JK. Protein-losing enteropathy: case illustrations and clinical review. Am J Gastroenterol. 2010;105:43-9; quiz 50.\u003c/li\u003e\n\u003cli\u003eOzen A, Lenardo MJ. Protein-Losing Enteropathy. N Engl J Med. 2023;389:733-48.\u003c/li\u003e\n\u003cli\u003eWang YF, Tseng KC, Chiu JS, et al. Outcome of surgical resection for protein-losing enteropathy in systemic lupus erythematosus. Clin Rheumatol. 2008;27:1325-8.\u003c/li\u003e\n\u003cli\u003eItkin M, Piccoli DA, Nadolski G, et al. Protein-Losing Enteropathy in Patients With Congenital Heart Disease. J Am Coll Cardiol. 2017;69:2929-37.\u003c/li\u003e\n\u003cli\u003eOrozco J, Nguyen J, Yasrebi SM, et al. Severe gastrointestinal manifestations in childhood-onset lupus: A single-center cohort and review of the literature. Lupus. 2025;34:721-41.\u003c/li\u003e\n\u003cli\u003ePeng L, Li Z, Xu D, et al. Characteristics and Long-term Outcomes of Patients with Lupus-related Protein-losing Enteropathy: A Retrospective Study. Rheumatol Immunol Res. 2020;1:47-52.\u003c/li\u003e\n\u003cli\u003eBhatnagar A, Singh AK, Lahoti D, et al. Technetium-99m dextran: a promising new protein-losing enteropathy imaging agent. Eur J Nucl Med. 1996;23:575-8.\u003c/li\u003e\n\u003cli\u003eChiu NT, Lee BF, Hwang SJ, et al. Protein-losing enteropathy: diagnosis with (99m)Tc-labeled human serum albumin scintigraphy. Radiology. 2001;219:86-90.\u003c/li\u003e\n\u003cli\u003eHalaby H, Bakheet SM, Shabib S, et al. 99mTc-human serum albumin scans in children with protein-losing enteropathy. J Nucl Med. 2000;41:215-9.\u003c/li\u003e\n\u003cli\u003eHsu YJ, Lin SH, Lin YF, et al. Pitfalls of technetium-99m-labeled human serum albumin scintigraphy for protein-losing enteropathy. Kidney Int. 2009;76:911; author reply -2.\u003c/li\u003e\n\u003cli\u003eOkahara M, Kiyosue H, Miyake H, et al. [Evaluation of 99mTc-DTPA-HSA abdominal imaging of protein-losing gastroenteropathy]. Nihon Igaku Hoshasen Gakkai Zasshi. 1998;58:277-80.\u003c/li\u003e\n\u003cli\u003eSeok JW, Kim S, Lee SH, et al. Protein-losing enteropathy detected on Tc-99m HSA and Tc-99m MDP scintigraphy. Clin Nucl Med. 2002;27:431-3.\u003c/li\u003e\n\u003cli\u003eTakeda H, Takahashi T, Ajitsu S, et al. Protein-losing gastroenteropathy detected by technetium-99m-labeled human serum albumin. Am J Gastroenterol. 1991;86:450-3.\u003c/li\u003e\n\u003cli\u003eHubalewska-Hoła A, Sowa-Staszczak A, Szczerbiński T, et al. [Protein losing enteropathy (PLE) detected by Tc99m-labelled human serum albumin abdominal scintigraphy--case report]. Przegl Lek. 2003;60:606-8.\u003c/li\u003e\n\u003cli\u003eChau TN, Mok MY, Chan EY, et al. Evaluation of performance of measurement of faecal \u0026alpha;(1)-antitrypsin clearance and technetium-99m human serum albumin scintigraphy in protein-losing enteropathy. Digestion. 2011;84:199-206.\u003c/li\u003e\n\u003cli\u003eDivgi CR, Lisann NM, Yeh SD, et al. Technetium-99m albumin scintigraphy in the diagnosis of protein-losing enteropathy. J Nucl Med. 1986;27:1710-2.\u003c/li\u003e\n\u003cli\u003eKoizumi K, Masaki H, Matsuda H, et al. Japanese consensus guidelines for pediatric nuclear medicine. Part 1: Pediatric radiopharmaceutical administered doses (JSNM pediatric dosage card). Part 2: Technical considerations for pediatric nuclear medicine imaging procedures. Ann Nucl Med. 2014;28:498-503.\u003c/li\u003e\n\u003cli\u003eAl Balushi A, Mackie AS. Protein-Losing Enteropathy Following Fontan Palliation. Can J Cardiol. 2019;35:1857-60.\u003c/li\u003e\n\u003cli\u003eConnor FL, Angelides S, Gibson M, et al. Successful resection of localized intestinal lymphangiectasia post-Fontan: role of (99m)technetium-dextran scintigraphy. Pediatrics. 2003;112:e242-7.\u003c/li\u003e\n\u003cli\u003eIshigami S, King G, Buratto E, et al. Outcomes of extracardiac Fontan operation: A single institution experience with 398 patients. J Thorac Cardiovasc Surg. 2025;169:400-10.e7.\u003c/li\u003e\n\u003cli\u003eMauro A, Giani T, Di Mari C, et al. Gastrointestinal Involvement in Children with Systemic Lupus Erythematosus. Children (Basel). 2023;10.\u003c/li\u003e\n\u003cli\u003evan Hoeve K, De Keukelaere M, De Hertogh G, et al. Child with protein losing enteropathy as presentation of collagenous duodenitis and eosinophilic gastroenteritis. Acta Gastroenterol Belg. 2023;86:363-6.\u003c/li\u003e\n\u003cli\u003eChehade M, Magid MS, Mofidi S, et al. Allergic eosinophilic gastroenteritis with protein-losing enteropathy: intestinal pathology, clinical course, and long-term follow-up. J Pediatr Gastroenterol Nutr. 2006;42:516-21.\u003c/li\u003e\n\u003cli\u003eMertens L, Hagler DJ, Sauer U, et al. Protein-losing enteropathy after the Fontan operation: an international multicenter study. PLE study group. J Thorac Cardiovasc Surg. 1998;115:1063-73.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"annals-of-nuclear-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"anme","sideBox":"Learn more about [Annals of Nuclear Medicine](http://link.springer.com/journal/12149)","snPcode":"12149","submissionUrl":"https://www.editorialmanager.com/anme/default2.aspx","title":"Annals of Nuclear Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Protein losing enteropathy, Fontan, nuclear medicine, scintigraphy, Technetium-99m Albumin scintigraphy","lastPublishedDoi":"10.21203/rs.3.rs-7088989/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7088989/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e\u003cp\u003eThis study aimed to demonstrate the differences in Technetium-99m albumin scintigraphy findings for patients with protein-losing enteropathy (PLE) associated with their characteristics and laboratory data.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eEighteen patients with PLE were grouped into two based on two mechanisms: direct mucosal damage and failed lymph drainage. Scintigraphy images were divided based on the timing of acquisition: dynamic images obtained within the first hour; and images obtained at 2, 4, 6, and 24 h after starting the examination. The intensity of tracer uptake was graded as follows: 3 (marked uptake equal to or greater than the liver level), 2 (moderate uptake less than liver and greater than kidney levels), 1 (mild uptake less than kidney level), and 0 (negative). The grades at each timepoint for the two groups were compared using the Mann-Whitney U test. The associations between the grades and fecal alfa-1-antitrypsin and serum total protein concentrations were evaluated using Pearson correlation coefficients.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eOf 18 patients, 7 had PLE due to failed lymph drainage. The direct mucosal damage and failed lymph drainage groups had significantly different fecal alfa-1-antitrypsin concentrations (43.5\u0026thinsp;\u0026plusmn;\u0026thinsp;29.6 [range, 11\u0026ndash;115] vs. 208.7\u0026thinsp;\u0026plusmn;\u0026thinsp;66.0 [range, 124\u0026ndash;311], respectively; P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and scintigraphy-based severity at 24 h (1.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.8 [range, 1\u0026ndash;3] vs. 2.8\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4 [range, 2\u0026ndash;3], respectively; P\u0026thinsp;=\u0026thinsp;0.007). The fecal alpha-1-antitrypsin concentration was positively correlated with the scintigraphy-based severity at 6 h (r\u0026thinsp;=\u0026thinsp;0.499, P\u0026thinsp;=\u0026thinsp;0.049) and 24 h (r\u0026thinsp;=\u0026thinsp;0.747, P\u0026thinsp;=\u0026thinsp;0.002). However, the serum protein concentration was negatively correlated with the scintigraphy-based severity at 6 h (r = -0.587, P\u0026thinsp;=\u0026thinsp;0.017).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003eThe scintigraphy-based severity at 6 and 24 h and the fecal alpha-1 antitrypsin concentrations were higher for patients with PLE due to failed lymph drainage mechanisms than for those with PLE due to direct mucosal damage. Scintigraphy can help localize the leakage point and determine disease severity to guide PLE management.\u003c/p\u003e","manuscriptTitle":"Association between technetium-99m albumin scintigraphy-based severity of protein-losing enteropathy and patient characteristics and laboratory data","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-18 13:11:40","doi":"10.21203/rs.3.rs-7088989/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"","date":"2025-07-14T22:22:17+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-07-14T05:58:38+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-07-10T06:30:51+00:00","index":"","fulltext":""},{"type":"submitted","content":"Annals of Nuclear Medicine","date":"2025-07-10T01:07:19+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"annals-of-nuclear-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"anme","sideBox":"Learn more about [Annals of Nuclear Medicine](http://link.springer.com/journal/12149)","snPcode":"12149","submissionUrl":"https://www.editorialmanager.com/anme/default2.aspx","title":"Annals of Nuclear Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"2e2b2789-ea75-48cd-8dd7-4b2804042783","owner":[],"postedDate":"July 18th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-09-29T15:59:38+00:00","versionOfRecord":{"articleIdentity":"rs-7088989","link":"https://doi.org/10.1007/s12149-025-02109-5","journal":{"identity":"annals-of-nuclear-medicine","isVorOnly":false,"title":"Annals of Nuclear Medicine"},"publishedOn":"2025-09-22 15:57:14","publishedOnDateReadable":"September 22nd, 2025"},"versionCreatedAt":"2025-07-18 13:11:40","video":"","vorDoi":"10.1007/s12149-025-02109-5","vorDoiUrl":"https://doi.org/10.1007/s12149-025-02109-5","workflowStages":[]},"version":"v1","identity":"rs-7088989","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7088989","identity":"rs-7088989","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}