Relationship Between Gastrointestinal Transit, Medsger Gastrointestinal Severity, and University of California-Los Angeles Scleroderma Clinical Trial Consortium Gastrointestinal Tract 2.0 Symptoms in Patients With Systemic Sclerosis.

OBJECTIVE: Systemic sclerosis (SSc)-associated gastrointestinal (GI) complications are attributed to a variety of factors, including diet, microbiota dysbiosis, or GI transit abnormalities. Our objective was to examine the contribution of abnormal GI transit to SSc Medsger GI severity scores and/or University of California Los Angeles Scleroderma Clinical Trial Consortium Gastrointestinal Tract (UCLA GIT) 2.0 symptoms. METHODS: Patients with SSc and GI symptoms (n = 71) and healthy controls (n = 18) underwent whole gut transit (WGT) scintigraphy to assess transit from the esophagus to the colon. The presence of delayed transit and percent emptying in each GI region were measured. We compared the WGT measurements between categories of the Medsger GI severity score (0-4) and across UCLA GIT 2.0 domains and total score (0-3). RESULTS: A total of 88% of patients had >1 abnormal region of the gut on WGT scintigraphy. All patients requiring total parenteral nutrition had delayed small bowel transit, compared to only approximately 11% of patients in other Medsger GI severity groups (P ≤ 0.01). Severe colonic transit delays were more likely in patients with Medsger GI scores of 3 (pseudo-obstruction and/or malabsorption) compared to other Medsger GI groups (P = 0.02). Seventy-percent of these patients had ≤30% colonic emptying at 72 hours. Modest associations were noted between gastroesophageal reflux disease symptoms and delayed esophageal (r = -0.31, P = 0.05) and gastric emptying (r = -0.32, P = 0.05). CONCLUSION: These data are important in providing evidence that SSc bowel disease affects transit of GI content and that delay in transit accounts in part for both bowel symptoms and Medsger GI severity. Prospective studies examining the benefit of early therapeutic intervention targeting GI transit abnormalities in patients at high risk for severe GI complications are needed.

Experience with Esophagogastrointestinal Transit Scintigraphy in the Initial 229 Patients: Multiple Regions of Dysmotility Are Common.

The purpose of this investigation was to review our experience with our comprehensive esophagogastrointestinal transit study in the first 229 patients. This scintigraphic study analyzes the motility of the entire gut, from the esophagus through the rectosigmoid colon. Methods: Data were reviewed for our first 2 y of experience with this examination (184 women and 45 men aged 20-79 y [mean ± SD, 44 ± 16 y]). Patients were referred with symptoms suggestive of a motility disorder. They first swallowed 111In-diethylenetriaminepentaacetic acid in water for the esophageal-swallow study and then 300 mL for a 30-min 111In water-only study, followed by 120 mL of 111In water simultaneously with the solid standardized 99mTc egg-substitute meal. Images and quantification were obtained for esophageal transit, water-only gastric emptying, water-with-solid gastric emptying, small-bowel transit, and colonic transit. Results: Of the 229 patient studies, 45 (20%) were normal. The remaining 184 (80%) had at least 1 region of dysmotility, for a total of 336 regions of abnormal motility. A single region of dysmotility was seen in 92 patients (50%), 2 regions in 50 (27%), 3 regions in 26 (14%), 4 regions in 12 (7%), and 5 regions in 4 (2%). There was a poor correlation between the results of the water-only study and water with the solid meal. Three different patterns of delayed colonic transit were seen. Patient symptoms were often not predictive of the scintigraphic findings. Conclusion: This study highlights the frequent occurrence of dysmotility in more than 1 region of the gastrointestinal tract in patients with a suspected motility disorder and the frequent concurrence of both upper- and lower-tract dysmotility in the same patients. It provides information to referring physicians regarding which motility disorders may be causing the patient symptoms, why the patient is or is not responding to the present therapy, and if and what additional workup and therapy may be needed.

EnsurePlus as an Alternative to the Standardized Egg Gastric-Emptying Meal.

OBJECTIVES: The purpose of this study was to establish normal gastric-emptying values for EnsurePlus in healthy subjects and to determine whether it is an acceptable alternative to the recommended standardized Tc-sulfur colloid egg meal. METHODS: Twenty-one healthy subjects underwent gastric-emptying scintigraphy with In-DTPA EnsurePlus. Normal gastric emptying values were established for 1, 2, 3, and 4 hours after meal ingestion. The gastric-emptying results were compared with another group of normal subjects (n = 18) who ingested the standardized egg meal. RESULTS: The mean (95% upper reference limit) percentages for gastric retention for EnsurePlus were as follows: 69.9% (87.1%) at 1 hour, 35.1% (64.3%) at 2 hours, 13.5% (23.2%) at 3, and 8.9% (13.5%) at 4 hours. There were time-related differences in the gastric emptying of the EnsurePlus compared with the egg meal. In the first and second hours, there were no difference between EnsurePlus and the egg meal in terms of percentage retention (P = 0.92 at 1 hour, P = 0.05 at 2 hours). However, at 3 and 4 hours after meal ingestion, the mean percentage gastric retention of the EnsurePlus was significantly higher than the egg meal (P < 0.001). CONCLUSION: EnsurePlus is a good and acceptable alternative to the standardized egg meal.

Sincalide: A Review of Clinical Utility, Proper Infusion Methodology, and Alternative Cholecystogogues.

Sincalide (Kinevac) is widely used in conjunction with cholescintigraphy for a variety of clinical indications. Over the years, numerous publications have verified the optimal infusion methodology. Published data and consensus recommendations emphasize that sincalide, 0.02 µg/kg, should be infused over 60 min. Production problems sometimes limit the availability of sincalide. In that case, non-Food and Drug Administration pharmacy-compounded sincalide may serve as an alternative. Fatty meals have also been used. Various illnesses and drugs may inhibit gallbladder contraction. Thus, these drugs should be withheld for 48 h before the study. Sincalide cholescintigraphy is most commonly used to diagnose or exclude chronic acalculous gallbladder disease. The study should preferably be performed as an outpatient procedure.

Nuclear Scintigraphy in Practice: Gastrointestinal Motility.

OBJECTIVE: The purpose of this article is to describe the clinical utility of state-of-theart gastrointestinal transit scintigraphy, including the standardized esophageal transit, solid and liquid gastric emptying, small-bowel transit, colon transit, and whole-gut transit scintigraphy, with an emphasis on procedure performance. CONCLUSION: Radionuclide gastrointestinal motility studies are noninvasive, quantitative, and physiologic diagnostic tools for evaluating patients with gastrointestinal complaints.

The Scintigraphic Drooping Lily Sign.

The "drooping lily" sign is identified on intravenous urography or voiding cystourethrography in patients with a duplicated renal collecting system and refers to inferolateral displacement of a functioning lower pole moiety by an obstructed upper pole collecting system. In this case, a 2-month-old girl with a prenatal diagnosis of hydronephrosis was found to have a "scintigraphic drooping lily" sign on Tc-dimercaptosuccinic acid renal scan. Evaluation with ultrasound and voiding cystourethrography confirmed a duplicated collecting system and obstructed upper pole moiety. Correlation with anatomic imaging can help avoid mistaking the scintigraphic "drooped" lower pole for an inferiorly positioned normal kidney.

Gastrointestinal Transit Assessment: Role of Scintigraphy: Where Are We Now? Where Are We Going?

OPINION STATEMENT: The diagnostic imaging evaluation of patients with suspected esophagogastrointestinal transit disorders is changing. Anatomical methods, e.g., barium studies, endoscopy, manometry, radiopaque markers, have long been the techniques available and used for diagnosis. The one exception has been gastric emptying, where radionuclide scintigraphy has been the standard for decades. Esophageal transit scintigraphy is an old and reliable methodology but probably underutilized. The diagnostic use of small and large intestinal transit scintigraphy is increasing, in part, because of the limitations of the other methods but, most importantly, because it is truly physiologic, i.e., the transit of radiolabeled food can be imaged and quantified from the mouth to rectum. Limitations to its wider use have been the lack of standardization, general availability, and reimbursement issues. Radionuclide methods are increasingly being used to evaluate esophagogastrointestinal transit in a single study, from top to bottom.

Early Antibiotic Treatment for Pediatric Febrile Urinary Tract Infection and Renal Scarring.

IMPORTANCE: Existing data regarding the association between delayed initiation of antimicrobial therapy and the development of renal scarring are inconsistent. OBJECTIVE: To determine whether delay in the initiation of antimicrobial therapy for febrile urinary tract infections (UTIs) is associated with the occurrence and severity of renal scarring. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study that combined data from 2 previously conducted longitudinal studies (the Randomized Intervention for Children With Vesicoureteral Reflux trial and the Careful Urinary Tract Infection Evaluation Study). Children younger than 6 years with a first or second UTI were followed up for 2 years. EXPOSURE: Duration of the child's fever prior to initiation of antimicrobial therapy for the index UTI. MAIN OUTCOMES AND MEASURES: New renal scarring defined as the presence of photopenia plus contour change on a late dimercaptosuccinic acid renal scan (obtained at study exit) that was not present on the baseline scan. RESULTS: Of the 482 children included in the analysis, 434 were female (90%), 375 were white (78%), and 375 had vesicoureteral reflux (78%). The median age was 11 months. A total of 35 children (7.2%) developed new renal scarring. Delay in the initiation of antimicrobial therapy was associated with renal scarring; the median (25th, 75th percentiles) duration of fever prior to initiation of antibiotic therapy in those with and without renal scarring was 72 (30, 120) and 48 (24, 72) hours, respectively (P = .003). Older age (OR, 1.03; 95% CI, 1.01-1.05), Hispanic ethnicity (OR, 5.24; 95% CI, 2.15-12.77), recurrent urinary tract infections (OR, 0.97; 95% CI, 0.27-3.45), and bladder and bowel dysfunction (OR, 6.44; 95% CI, 2.89-14.38) were also associated with new renal scarring. Delay in the initiation of antimicrobial therapy remained significantly associated with renal scarring even after adjusting for these variables. CONCLUSIONS AND RELEVANCE: Delay in treatment of febrile UTIs and permanent renal scarring are associated. In febrile children, clinicians should not delay testing for UTI.

Utility of sedation for young children undergoing dimercaptosuccinic acid renal scans.

BACKGROUND: No studies have examined whether use of sedation during a Tc-99 m dimercaptosuccinic acid (DMSA) renal scan reduces patient discomfort. OBJECTIVE: To compare discomfort level during a DMSA scan to the discomfort level during other frequently performed uroradiologic tests, and to determine whether use of sedation during a DMSA scan modifies the level of discomfort. MATERIALS AND METHODS: We examined the discomfort level in 798 children enrolled in the Randomized Intervention for children with Vesicoureteral Reflux (RIVUR) and Careful Urinary Tract Infection Evaluation (CUTIE) studies by asking parents to rate their child's discomfort level with each procedure on a scale from 0 to 10. We compared discomfort during the DMSA scan and the DMSA image quality between centers in which sedation was used >90% of the time (sedation centers), centers in which sedation was used <10% of the time (non-sedation centers), and centers in which sedation was used on a case-by-case basis (selective centers). RESULTS: Mean discomfort level was highest for voiding cystourethrogram (6.4), followed by DMSA (4.0), followed by ultrasound (2.4; P<0.0001). Mean discomfort level during the DMSA scan was significantly higher at non-sedation centers than at selective centers (P<0.001). No difference was apparent in discomfort level during the DMSA scan between sedation centers and selective centers (P=0.12), or between the sedation centers and non-sedation centers (P=0.80). There were no differences in the proportion with uninterpretable DMSA scans according to sedation use. CONCLUSION: Selective use of sedation in children 12-36 months of age can reduce the discomfort level experienced during a DMSA scan.

Renal Scarring in the Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) Trial.

BACKGROUND AND OBJECTIVES: The main objectives of the Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) trial were to evaluate the role of antimicrobial prophylaxis in the prevention of recurrent urinary tract infection (UTI) and renal scarring in children with vesicoureteral reflux (VUR). We present a comprehensive evaluation of renal scarring outcomes in RIVUR trial participants. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This multicenter, randomized, placebo-controlled trial enrolled 607 children aged 2-71 months with grade 1-4 VUR diagnosed after a first or second febrile or symptomatic UTI. Study participants received trimethoprim-sulfamethoxazole or placebo and were followed for 2 years. Renal scarring was evaluated by baseline and follow-up (99m)technetium dimercaptosuccinic acid (DMSA) renal scans that were reviewed independently by two blinded reference radiologists. RESULTS: At the end of the study, 58 (10%) of 599 children and 63 (5%) of 1197 renal units had renal scarring. New renal scarring did not differ between the prophylaxis and placebo groups (6% versus 7%, respectively). Children with renal scarring were significantly older (median age, 26 versus 11 months; P=0.01), had a second UTI before enrollment (odds ratio [OR], 2.85; 95% confidence interval [95% CI], 1.38 to 5.92), were more likely to be Hispanic (OR, 2.22; 95% CI, 1.13 to 4.34), and had higher grades of VUR (OR, 2.79; 95% CI, 1.56 to 5.0). The proportion of new scars in renal units with grade 4 VUR was significantly higher than in units with no VUR (OR, 24.2; 95% CI, 6.4 to 91.2). CONCLUSIONS: Significantly more renal scarring was seen in relatively older children and in those with a second episode of febrile or symptomatic UTI before randomization. Preexisting and new renal scars occurred significantly more in renal units with grade 4 VUR than in those with low-grade or no VUR. Antimicrobial prophylaxis did not decrease the risk of renal scarring.

Comprehensive radionuclide esophagogastrointestinal transit study: methodology, reference values, and initial clinical experience.

UNLABELLED: A radionuclide methodology and reference values have been developed for a single gastrointestinal transit study including esophageal transit, liquid and solid gastric emptying, and small- and large-bowel transit, using (111)In-diethylenetriaminepentaacetic acid (DTPA) with the standardized (99m)Tc-labeled solid meal. METHODS: Eighteen healthy subjects and 18 patients were investigated. The esophageal transit study was performed with 3.7 MBq (0.1 mCi) of (111)In-DTPA in 15 mL of water. A liquid-only 30-min gastric-emptying study followed, with ingestion of 3.7 MBq (0.1 mCi) of (111)In-DTPA in 300 mL of water. Then, a simultaneous solid-liquid emptying study was acquired after ingestion of a solid (99m)Tc-sulfur colloid-labeled meal and 7.4 MBq (0.2 mCi) of (111)In-DTPA in 120 mL of water. Images were acquired intermittently for 4 h. Additional (111)In images were acquired at 5 and 6 h to measure small-bowel transit, and at 24, 48, and 72 h for large-bowel transit. RESULTS: Reference values were determined for esophageal transit (transit time, percentage emptying at 10 s), liquid-only gastric emptying (emptying half-time), liquid and solid emptying in a dual-phase solid-liquid study (emptying half-time and percentage emptying at 1, 2, 3, and 4 h), small-bowel transit index (percentage transit to ileocecal valve at 6 h), and colonic transit (geometric center and percentage colonic emptying) at 24, 48, and 72 h. Results from the first 18 patients found abnormal transit in 72% (13/18); clinical management changed in 61% (11/18). CONCLUSION: We have developed a radionuclide methodology and derived reference values for a comprehensive gastrointestinal transit study using (111)In-DTPA with the standardized (99m)Tc-labeled solid meal. Our initial clinical experience suggests clinical value.

Hepatobiliary scintigraphy in 2014.

Cholescintigraphy with (99m)Tc-hepatobiliary radiopharmaceuticals has been an important, clinically useful diagnostic imaging study for almost 4 decades. It continues to be in much clinical demand; however, the indications, methodology, and interpretative criteria have evolved over the years. This review will emphasize state-of-the-art methodology and diagnostic criteria for various clinical indications, including acute cholecystitis, chronic acalculous gallbladder disease, high-grade and partial biliary obstruction, and the postcholecystectomy pain syndrome, including sphincter-of-Oddi dysfunction and biliary atresia. The review will also emphasize the use of diagnostic pharmacologic interventions, particularly sincalide.

Hepatobiliary scintigraphy in 2014.

Cholescintigraphy with (99m)Tc-hepatobiliary radiopharmaceuticals has been an important, clinically useful diagnostic imaging study for almost 4 decades. It continues to be in much clinical demand; however, the indications, methodology, and interpretative criteria have evolved over the years. This review will emphasize state-of-the-art methodology and diagnostic criteria for various clinical indications, including acute cholecystitis, chronic acalculous gallbladder disease, high-grade and partial biliary obstruction, and the postcholecystectomy pain syndrome, including sphincter-of-Oddi dysfunction and biliary atresia. The review will also emphasize the use of diagnostic pharmacologic interventions, particularly sincalide.

Clinical significance of discordant findings between pre-therapy (123)I and post-therapy (131)I whole body scan in patients with thyroid cancer.

Radioactive therapy with (131)I (RAI) is commonly used during the management of patients with differentiated thyroid cancer (DTC). The aim of this study was to determine the clinical significance of discordant findings between pre-RAI whole body scan (WBS) with (123)I and post-RAI WBS in the management of DTC. We retrospectively evaluated 342 individuals between 2002 and 2008 who had a diagnosis of DTC and underwent RAI. All had WBS one day before RAI and WBS one week after RAI. Patients were divided into 3 groups: 1) RAI-naive subjects without known distant metastatic disease (M1); 2) patients with history of prior RAI and persistent disease (except M1); and 3) patients with known M1. In Group 1 (n=311), 7% of patients (n=22) had discordant scans, but in only 4 of these cases did this represent true disease (3 unsuspected lung and 1 mediastinal node metastasis). In the remaining 18 patients, discordant findings corresponded to physiologic or other benign causes. In group 2 (n=23), 7 subjects (30%) had discordant findings and all of the discrepant sites consisted of loco-regional nodal disease in the neck/upper mediastinum (n=6) and M1 in lung (n=1). In group 3 (n=8), 5 patients (62%) showed discordant uptake in lung and bone which corresponded to the locations of known M1. A total of 12 patients with iodine-avid M1 were identified on post-RAI WBS (3.5% of entire cohort). Pre-RAI WBS was only concordant in 3 of these cases (25%). In conclusion, the significance of pre and post-RAI WBS is highly influenced by the clinical setting. Unsuspected distant metastatic disease is infrequent in RAI-naive patients without known M1, where most discordant findings are usually due to benign explanations, and represent false positive findings in this group. In contrast, in patients with history of previous RAI or known M1, discordant results likely correspond to true disease. In our study, pre-RAI scans showed a low yield to detect iodine-avid distant metastatic disease when compared to post-RAI scans.

Sincalide cholescintigraphy--32 years later: evidence-based data on its clinical utility and infusion methodology.

Sincalide cholescintigraphy was first reported to have clinical utility in 1980. Since then, many publications have found that a reduced gallbladder ejection fraction (GBEF) can confirm the clinical diagnosis of acalculous chronic gallbladder disease and predict symptomatic relief with cholecystectomy. However, some publications had not found the test clinically predictive. Many different sincalide infusion methods and normal values have been used. It had been suspected that the different infusion methods and normal values might account for the variability in reported utility. Furthermore, clinical review articles have raised questions about the evidence-based quality of the published data on the diagnostic utility of sincalide cholescintigraphy. A recently published multicenter trial has established the optimal methodology for sincalide infusion and normal values. A subsequent multispecialty consensus publication has recommended that this method be the standard method for sincalide infusion, specifically, a 60-minute infusion of 0.02 µg/kg (abnormal GBEF, <38%). The consensus publication also recommended that a large, multicenter, randomized, prospective trial was needed to confirm the utility of a low GBEF to predict acalculous chronic gallbladder disease and the patient's response to cholecystectomy.

Cholecystokinin-cholescintigraphy in adults: consensus recommendations of an interdisciplinary panel.

BACKGROUND AND AIMS: Cholecystokinin-cholescintigraphy (CCK-CS) provides a physiologic, noninvasive, and quantitative method for assessing gallbladder contraction and calculation of a gallbladder ejection fraction (GBEF). At present, it is used most commonly to identify patients with suspected functional gallbladder disorder. However, the methodology of CCK infusion and normal values differ markedly among imaging centers. METHODS: This document represents the consensus opinion of an interdisciplinary panel that gathered to assess the current optimal method for performing CCK-CS in adults, potential uses and limitations of CCK-CS, and questions that require further investigation. RESULTS: The panel recommended the use of a single, standardized, recently described CCK-CS protocol that involves infusion of 0.02 µg/kg of sincalide over 60 minutes with a normal GBEF defined as ≥38%. The panel emphasized the need for a large, multicenter, prospective clinical trial to establish the utility of CCK-CS in the diagnosis of functional gallbladder disease. Although not without controversy regarding its clinical utility, the primary indication for CCK-CS at present is the well-selected patient with suspected functional gallbladder disorder. CONCLUSION: Agreement was reached that the adoption of this standardized protocol is critical to improve how CCK-CS is used to direct patient care and will represent an improvement over the diverse methods currently in use by eliminating the current lack of uniformity and adding both reliability and credibility to the results.