in Patients Without Overt Gastrointestinal Disease

Transcription

1 Gastrointestinal Imaging Original Research Gervaise et al. Gastric Wall Fatty Infiltration Gastrointestinal Imaging Original Research Alban Gervaise 1 Pierre Naulet 1 Christelle Gervaise-Henry 2 Camille Junca-Laplace 1 Matthieu Pernin 1 Marie Lapierre-Combes 1 Gervaise A, Naulet P, Gervaise-Henry C, Junca-Laplace C, Pernin M, Lapierre-Combes M Keywords: CT, fat, gastric, stomach, wall DOI: /AJR Received June 18, 2015; accepted after revision September 1, Department of Radiology, Legouest Military Hospital, BP 90001, Metz Cedex 3, France. Address correspondence to A. Gervaise (alban.gervaise@hotmail.fr). 2 Biochemistry Laboratory, Centre Hospitalier Universitaire, Nancy, France. AJR 2016; 206: X/16/ American Roentgen Ray Society Gastric Wall Fatty Infiltration in Patients Without Overt Gastrointestinal Disease OBJECTIVE. The purpose of this study was to evaluate the frequency of gastric wall fatty infiltration in patients without overt gastrointestinal disease. MATERIALS AND METHODS. A retrospective study included patients who underwent unenhanced MDCT for renal colic. Two radiologists reviewed all of the images and evaluated for the presence of gastric wall fatty infiltration. The following patient characteristics were also recorded: sex, age, body mass index, total and visceral fat area, and presence of colic or ileal fat halo sign, or hepatic steatosis. A t test and Fisher test were used to compare the results between patients with and patients without gastric wall fatty infiltration. RESULTS. Gastric wall fatty infiltration was present in 25 of 120 (21%) patients in the study. Mean age, weight, body mass index, visceral and total fat areas, proportion of hepatic steatosis, number of men, and frequency of the presence of colic and ileal fat halo signs were significantly higher among patients with gastric wall fatty infiltration than in those without infiltration. CONCLUSION. Gastric wall fatty infiltration was significantly more frequent in men older than 45 years and patients with a body mass index greater than 25. It may represent a normal finding, but its relation to other pathologic conditions related to obesity remains to be explored. T he fat halo sign corresponds to a deposition of fat in the submucosal layer of the walls of the colon and small bowel [1]. This sign was initially described in CT examinations of patients with chronic inflammatory bowel disease [2 5]. For some authors, the presence of a smallbowel fat halo sign was deemed highly indicative of Crohn disease [6]. Cases that are more atypical have also been described, including the acute appearance of this fatty infiltration in patients undergoing cytoreduction therapy and patients with graft versus host disease [4, 7]. When only the colon is affected, ulcerative colitis should also be considered [2]. However, in a 2003 report of a study that included 100 patients without intestinal disease, Harisinghani et al. [8] noted that a fat halo sign was seen in the CT examinations of 21% of the patients. They concluded that the presence of the fat halo sign may be a normal finding related to obesity. A single study in which only the normal range of wall thickness and appearance of the wall of the gastric antrum were analyzed showed that the stomach can also exhibit fatty infiltration of the submucosal layer of the gastric wall [9]. To our knowledge, no study has assessed the presence of this fatty infiltra- tion throughout the entire gastric wall, and no study has been conducted to define the underlying factors. The aim of our study was to assess the frequency of gastric wall fatty infiltration among patients without gastrointestinal disease and to determine the underlying factors that result in the occurrence of this fatty infiltration. Materials and Methods This retrospective study was approved by our local ethics committee. Because of the retrospective nature of the study, written consent from the patients was not required. Study Population The selection of patients was performed in a retrospective manner through the PACS at our military hospital (Impax V6, ES, Agfa Technical Imaging Systems) to access the entire collection of abdominopelvic CT examinations performed between January 1, 2012, and December 31, The next step was to select only unenhanced abdominopelvic CT examinations performed because of clinical suspicion of renal colic and in which the FOV comprised all of the stomach. For patients who underwent several CT examinations to evaluate renal colic during the inclusion period, only the first examination was included in this 734 AJR:206, April 2016

2 Gastric Wall Fatty Infiltration study. For all included patients, the following data were collected in a systematic way at the CT examination: sex, age (years), weight (kilograms), and height (meters). The body mass index (BMI) was determined according to the formula weight in kilograms divided by the square of height in meters. Patients with a BMI of 30 or greater were considered obese; patients with a BMI of 25 or greater but less than 30 were considered overweight [10]. CT Acquisition and Reconstruction Techniques All examinations were performed with a 64-MDCT scanner (Optima CT660, GE Healthcare) with the patient supine. No bowel or gastric preparation was used, such as ingestion of water or contrast agents in particular, nor were the patients asked to fast. The CT examinations were performed with a helical craniocaudal acquisition without contrast injection. The acquisition was centered on the urinary tract with a tube voltage fixed at 100 or 120 kv; automatic tube current modulation was performed in the x-, y-, and z-axes (SmartmA, GE Healthcare) with a noise index between 25 and 50. The other acquisition parameters were constant for the patients: section thickness, 1.25 mm; rotation time, 0.7 second; pitch, The images were reconstructed by adaptive statistical iterative reconstruction at 50% with a soft reconstruction filter, slice thickness of 1.25 mm, and a slice interval of 1.25 mm. The slice thickness was set at 1.25 mm according to our standard abdominopelvic CT protocol to maintain good spatial resolution and to allow good quality of multiplanar reformations. All of the images were sent directly to our PACS. Image Analysis Unenhanced CT images were analyzed by two senior radiologists with 9 and 6 years of experience Fig year-old man with renal colic. Unenhanced abdominal CT image shows thin linear fatty infiltration in submucosal layer of gastric wall with attenuation value less than 10 HU (average value of ROI 1 in greater curvature, 30 HU). Hepatic steatosis is also present (average value of right hepatic ROI 2, 31.7 HU). in reading abdominopelvic CT images. These two readers were not involved in patient selection. The two readers performed their interpretations independently using images from anonymous CT examinations. They read the images at the postprocessing workstation (ADW 4.6, GE Healthcare). The readers had the option of using all of the available visualization and calculation tools. They could increase slice thickness, display multiplanar reformats, zoom in on the image, change the window of visualization, and measure attenuation values within ROIs for which they could determine the size. During the reading session, the readers were asked to state whether there was fatty infiltration of the wall of the stomach, the colon, or terminal ileum. Gastric wall fatty infiltration was defined as thin linear fatty infiltration in the submucosal layer of the gastric wall with an attenuation value less than 10 HU [8] (Fig. 1). The readers were asked to specify the topography of the gastric wall fatty infiltration: fundus, greater curvature, lesser curvature, antropyloric junction. Fatty infiltration of the walls of the colon and terminal ileum was defined as the presence of fatty infiltration in the submucosal layer that involved more than threefourths of the circumference of the wall with an attenuation value less than 10 HU [8]. The readers were also asked to specify the affected sections: rectum, sigmoid colon, descending colon, transverse colon, ascending colon, and the last 30 cm of terminal ileum. In discordant cases, the two readers conducted a second reading session together to reach a consensus. On the basis of the two readers observations, the patients were separated into two groups: one with gastric wall fatty infiltration that was either diffuse or focal and other without gastric wall fatty infiltration. Final Diagnosis of Renal Colic and Previous Conditions For each examination, the lead investigator (8 years of experience in abdominopelvic CT reading) A Fig year-old woman with renal colic suspicion. Measurement of total and visceral fat areas. A, Unenhanced CT image with transverse slice at umbilical level. B, Postprocessed CT image shows first segmentation step performed on slice to retain only fat located inside muscles of abdominal wall. B (Fig. 2 continues on next page) AJR:206, April

3 Gervaise et al. C Fig. 2 (continued) 52-year-old woman with renal colic suspicion. Measurement of total and visceral fat areas. C, Postprocessed CT image shows second threshold step to retain only pixels of fat density with attenuation value between 190 and 30 HU. Visceral fat area corresponding to surface in square centimeters of ROI located on all remaining pixels. D, Postprocessed CT image shows total fat area determined from same section as C by application of threshold step only. established the final diagnosis of renal colic. This investigator had access to the entire patient database, including the unenhanced CT images and possible additional acquisitions with or without contrast administration. He also had access to the clinical, biologic, and follow-up information available in the institutional medical database (follow-up CT, complementary ultrasound or MRI, reports of medical appointments, and surgical reports). This study investigator also analyzed the medical information of each patient to verify whether the patient was known to have, or was undergoing monitoring for, chronic inflammatory intestinal disease or a gastric pathologic condition going back months. CT Assessment of Hepatic Steatosis The lead investigator measured liver attenuation in a standardized manner at the postprocessing workstation using a previously validated method [11]. A standard ROI of approximately 200 mm 2 was placed in a homogeneous area of the right hepatic lobe, avoiding vessels and focal lesions (Fig. 1). Hepatic steatosis was defined by a liver attenuation value of 40 HU or less [12, 13]. Measurement of the Total and Visceral Fat Areas The amount of visceral fat was determined by measuring the visceral fat area within the transverse cross section at the umbilical level [14]. The lead study investigator performed this measurement in a standardized manner at the postprocessing workstation. A first-segmentation step was used on the section to retain only the fat located inside the muscles of the abdominal wall. A second threshold step was used to retain only the pixels of fat density with an attenuation value between 190 and 30 HU [15]. The visceral fat area corresponded to the surface in square centimeters of an ROI located on all the remaining pixels of the section. The total fat area was then determined from the same section by application of only the threshold step to retain only the pixels of fat density (Fig. 2). Statistical Analysis The data were analyzed with R software for Microsoft Windows (R Foundation). The t test and the Fisher exact test were used to compare the differences between the two groups. Odds ratios were determined by univariate analysis. A value of p < Fig. 3 Chart shows anatomic distribution of gastric wall fatty infiltration (n = 120). Frequency (%) All 0.05 was considered to represent a statistically significant difference. Results The study included 120 patients. The patient characteristics are shown in Table 1. Out of the 120 patients, 51 (42%) had a final diagnosis of renal colic. Among the 69 patients who did not have renal colic, 37 differential diagnoses were found. In six cases, these diagnoses related to digestive abnormalities: two cases of acute appendicitis, one case of acute sigmoid diverticulitis, one of gastric ulcer, one of colitis, and one of ileal infection. None of these six patients had gastric wall fatty infiltration. Fundus Greater Curvature Lesser Curvature Antropyloric Region D 736 AJR:206, April 2016

4 Gastric Wall Fatty Infiltration TABLE 1: Patient Characteristics Gastric Wall Fatty Infiltration Characteristic Among all of the patients, 25 (21%) had gastric wall fatty infiltration (21 men, four women; mean age, 53.6 years; mean BMI, 29.6) (Table 1). Nine of these 25 patients (36%) were obese, and 12 (48%) were overweight. Gastric wall fatty infiltration was most often located at the level of the greater curvature (92%), then the level of the antropyloric junction (68%) (Fig. 3). Twelve of the 25 patients (48%) had diffuse fatty infiltration of the entire gastric wall, whereas 13 patients (52%) presented a localized fat deposition. Among the seven patients who had only one site affected, in five cases the condition was limited to the greater curvature, and in two cases it occurred only at the antropyloric junction. None of the 25 patients with gastric wall fatty infiltration had previous medically significant conditions, such as chronic inflammatory bowel disease in Total Present No. of study participants a 120 (100) 25 (21) 95 (79) Age (y) 43.5 ± 15.1 (21 87) 53.6 ± 13.4 (29 84) 40.9 ± 14.4 (21 87) < Sex < Men Women Weight (kg) 76.3 ± 19.7 (38 165) 91.7 ± 20.8 (73 165) 72.3 ± 17.4 (38 145) < Height (cm) ± 10.2 ( ) 172 ± 14.9 ( ) 168 ± 8.6 ( ) NS Body mass index 26.1 ± 5.4 ( ) 29.6 ± 5.5 ( ) 25.2 ± 5.1 ( ) < Overweight or obese Present Absent Hepatic steatosis Present Absent Renal colic NS Present Absent Fat halo sign of colon < Present Absent Fat halo sign of the terminal ileum < Present Absent Visceral fat area (cm 2 ) ± 8.85 ( ) ± 7.93 ( ) ± 7.92 ( ) < Total fat area (cm 2 ) ± ( ) ± ( ) ± ( ) < Note Data are expressed as number of subjects or mean ± SD with range in parentheses. NS = not significant. a Value in parentheses is percentage. particular. Three patients had previous instances of gastroduodenal ulcers that had healed, and two had undergone colonoscopy that did not reveal signs of chronic inflammatory bowel disease. The distribution of hepatic steatosis, overweight, and renal colic between groups and the mean and SD for age, weight, height, BMI, and visceral and total fat areas are presented in Table 1. Mean age, weight, BMI, and total and visceral fat areas were significantly higher in the group with gastric wall fatty infiltration than in the group without infiltration. There were also a significantly larger number of patients who were overweight and obese or who had hepatic steatosis in the group with gastric wall fatty infiltration compared with the group without infiltration. The odds ratio analysis showed that the presence of a fat halo sign in the colon and Absent the terminal ileum was linked most closely with the presence of gastric wall fatty infiltration (Table 2). Discussion As Harisinghani et al. [8] did, we chose a patient cohort who had undergone CT to evaluate for renal colic. This allowed us to select patients who did not have overt chronic inflammatory bowel or stomach diseases. In our study, only one patient received a gastric ulcer diagnosis as the result of gastric endoscopy performed after CT, but she did not have fatty infiltration of the gastric wall. Among the patients with fatty infiltration of the stomach, three had already undergone gastroduodenal endoscopy for ulcers, and two had undergone colonoscopy, but none of these five endoscopies showed anomalies indicative of chronic inflammatory bowel disease. p AJR:206, April

5 Gervaise et al. TABLE 2: Odds Ratio of the Presence of Gastric Wall Fatty Infiltration Variable Odds Ratio 95% CI Male sex Age > 45 y Overweight Hepatic steatosis Fat halo sign in the colon Fat halo sign in the terminal ileum Total fat area > 40 cm Visceral fat area > 20 cm Outside of the setting of chronic inflammatory bowel disease, our results show that gastric wall fatty infiltration occurs fairly frequently, in our study in 21% of patients. In a study of only the antrum, Pickhardt and Asher [9] found gastric wall fatty infiltration in the CT examinations of 14 of 153 patients without symptoms. In our patient population, the frequency of fatty infiltration of the wall of the gastric antrum was slightly higher than that reported by Pickhardt and Asher (14% versus 9%). Even if it was not the objective of their study, Pickhardt and Asher also noted that they saw no fatty infiltration at other anatomic sites of the gastric wall. In our study, we found that 23 of the 25 patients had fatty infiltration at another site in addition to the gastric antrum. These contradictory results may be explained by the different conditions under which the CT examinations were performed. First, in the study by Pickhardt and Asher, all of the patients received a gastric preparation with distention of the stomach by oral administration of 1 L of water-soluble contrast material. This gastric distention could explain why the thin layer of fatty infiltration became unnoticeable in their CT examinations (Fig. 4). This explanation also fits with the work by Harisinghani et al. [8], who noted a loss of the fat halo sign in distended colon segments compared with the same nondistended colonic sites. In our study, we did not perform gastric preparation of any kind. Most of our patients had fasted, and their stomachs were collapsed, facilitating the analysis of fatty infiltration. The lack of gastric distention by contrast material also prevents artifacts that could hinder interpretation of images of the gastric wall. Second, unlike those of Pickhardt and Asher [9], our CT examinations were preformed without IV injection of an iodinated contrast agent. Thus, it is possible that enhancement of the gastric wall could modify its fat-density appearance. Last, in accordance with our standard abdominopelvic CT protocol, our examinations were performed in thin sections of 1.25 mm, whereas Pickhardt and Asher acquired thicker CT sections of 5 mm. The use of thicker sections could lead to partial volume artifacts and impede detection of fatty infiltration of the gastric wall. Our results also show that fatty infiltration of the gastric wall is nearly systematically associated with the presence of a fat halo sign in the colon and the terminal ileum. Thus, of the 25 patients in the group with gastric wall fatty infiltration, 21 had a fat halo sign in the colon, 19 in the rectum, and 21 in the terminal ileum. Only 1 of the 25 patients did not have a fat halo sign in the rectum, colon, or terminal ileum. Conversely, the proportion of fatty infiltration of the gastric wall was higher among patients who had fatty infiltration of the colonic wall and the terminal ileum. Similarly, the number of affected gastric segments was proportionally higher when segments of the colon were also affected. This association is consistent with a similar physiopathologic mechanism that underlies the presence of fatty infiltration in the stomach, colon, rectum, or terminal ileum. Furthermore, in the patients in our clinical practice and in other patients without chronic inflammatory bowel disease, we have similarly observed that this fat halo sign is detectable in the wall of the esophagus. Once again, to our knowledge, there has been no study evaluating this, and it would be interesting to know the frequency and the associated factors. Like Harisinghani et al. [8], we found that fatty infiltration of the gastric wall was significantly more common among men, older patients, and those who were overweight or obese. We found a strong association between fatty infiltration of the gastric wall and a larger amount of total or visceral fat. We also found that the proportion of hepatic steatosis was substantially higher among patients with fatty infiltration of the gastric wall than among patients without gastric wall fatty infiltration. Like Harisinghani et al. [8], we think that this fatty infiltration of the gastric wall is not pathologic. More generally, we believe that fatty infiltration of the walls of the digestive tract (e.g., colon, ileum, stomach, and even the esophagus) may be a sign of fat overload. It has been established that once the normal sites of fat storage in the subcutaneous or visceral adipose tissues have been filled, free fatty acids are released into the blood [16]. This mechanism is thought to underlie the occurrence of hepatic steatosis in obese patients [16]. In the same way, an increase in the blood concentration of free fatty acids could A B Fig year-old man with renal colic suspicion. A, Unenhanced abdominal CT image shows diffuse fat deposition in submucosal layer of gastric wall. B, Unenhanced CT image obtained 6 months before A shows stomach was distended and fat deposition was much less evident as thin layer (arrow). 738 AJR:206, April 2016

6 Gastric Wall Fatty Infiltration promote the deposition of fat in the submucosal layer of the digestive tract. The presence of fatty infiltration in the wall of the digestive tract could hence be a sign of excessive fat accumulation. Furthermore, it has been equally well established that visceral adipose tissue underlies the secretion of proatherogenic factors that result in increased atherosclerosis [17, 18], and this is a risk factor for cardiovascular diseases and type 2 diabetes [19]. It would be interesting to explore whether there could be an association between fatty infiltration of the gastric wall and the occurrence of a metabolic syndrome or a type 2 diabetes and to determine whether this fatty infiltration could be a risk factor or a marker for cardiovascular diseases. It would also be interesting to follow changes in this fatty infiltration in patients who observe health and dietary recommendations for weight loss, caloric restriction, or the use of medications and to determine whether regression in fatty infiltration of the gastric wall is accompanied by a reduction in risk of cardiovascular diseases. The finding of a link between fatty infiltration of the gastric wall and risk of cardiovascular disease, metabolic syndromes, or type 2 diabetes could lead to use of a more aggressive therapeutic approach to the treatment of patients with fatty infiltration of the digestive tract walls than for those who do not have fatty infiltration. There were several limitations to our study. First, it was retrospective and included a small number of patients. Owing to the retrospective design of our study, we cannot totally exclude the possibility that some of our patients may have had subclinical or overt inflammatory bowel or stomach disease. Moreover, we did not have access to laboratory investigations such as lipid dosage. It would be interesting to undertake a prospective study with a larger patient cohort to analyze whether there is a link between fatty infiltration of the gastric wall, metabolic syndrome, type 2 diabetes, and cardiovascular events. Second, in the context of clinical suspicion of renal colic, several of our CT examinations were performed according to a low-dose protocol, which increased the background noise on images. We do not believe that this loss of image quality could underlie shortcomings regarding the detection of gastric wall fatty infiltration. This seems to be in agreement with the higher frequency of fat halo sign that we found in our patients compared with those in the study by Harisinghani et al. [8]. Third, even though most of our patients had fasted, we did not provide specific instructions about fasting before the CT examinations. Some patients had eaten, and their stomachs were hence distended, and this might have decreased the rate of detection of fatty infiltration in the gastric wall. Furthermore, although CT is a powerful imaging technique for probing for fatty lesions, we did not have correlative anatomopathologic data to confirm that our finding was indeed fatty infiltration of the submucosal layer of the gastric wall. Last, although we used a low-dose technique for CT acquisition, use of CT for the evaluation and follow-up of gastric wall fatty infiltration may be limited owing to the potential effects of ionizing radiation. Conclusion Gastric wall fatty infiltration was found in 21% of our patients without overt gastrointestinal disease. This fatty infiltration is nearly always associated with a fat halo sign of the colon or terminal ileum, and it is also more common among men, patients older than 45 years, and patients with a BMI greater than 25. 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