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Clinical Investigations |
1 Nuclear Medicine, Department of Medical Radiology, University Hospital of Zurich, Zurich, Switzerland
2 Gastroenterology, Department of Internal Medicine, University Hospital of Zurich, Zurich, Switzerland
3 Department of Visceral and Transplantation Surgery, University Hospital of Zurich, Zurich, Switzerland
4 Department of Pathology, University Hospital of Zurich, Zurich, Switzerland
5 Department of Thoracic Surgery, University Hospital of Zurich, Zurich, Switzerland
6 Department of Otorhinolaryngology-Head and Neck Surgery, University Hospital of Zurich, Zurich, Switzerland
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONCONCLUSIONREFERENCES |
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Key Words: 18F-FDG PET/CT • gastrointestinal tract • incidentally detected lesions • gastrointestinal neoplasm
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONCONCLUSIONREFERENCES |
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Additionally, we investigated whether these incidental 18F-FDG PET/CT findings had a relevant impact on the clinical management of these patients.
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MATERIALS AND METHODS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONCONCLUSIONREFERENCES |
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Patients with incidental 18F-FDG accumulation in the GIT, which was associated with abnormal soft-tissue density or wall thickening on the concomitantly acquired CT, were included in the study. An 18F-FDG accumulation in the GIT was termed incidental only in patients who were referred for PET/CT with the diagnosis of a non-GIT disorder or in patients with a known GIT disease in whom 18F-FDG accumulation occurred in areas not consistent with the preexisting pathology.
One hundred five of 3,281 patients (64 men, 41 women; age range, 46–85 y; mean age, 62 y) showed incidental 18F-FDG PET/CT findings in the GIT. From these 105 eligible patients, 7 patients were excluded from further analysis because ensuing histologic examination revealed gastrointestinal metastases of preexisting gynecologic cancers (n = 5) and malignant melanoma (n = 2) Thus, 98 patients were included in our study.
PET/CT Protocol
Imaging was performed using an integrated PET/CT device (DISCOVERY LS; General Electric Medical Systems) combining the ability to acquire CT images and PET data of the same patient in 1 session. A General Electric Advance NXi PET scanner and a multislice helical CT scanner (LightSpeed Plus) were integrated in this dedicated system. The axes of both systems were mechanically aligned to coincide perfectly. Typically, 6 or 7 bed positions are obtained covering 867–1,011.5 mm of the body. This gave adequate coverage from head to pelvic floor in all patients examined. The arms of the patients were elevated above the abdomen to reduce beam-hardening artifacts at the level of the liver. As a standard procedure, all patients received oral x-ray contrast agent (1,000 mL of a 1.5% diluted barium sulfate suspension (Micropaque Scanner; Guerbet) 45 min before data acquisition. No bowel preparation regimen was applied for any patient in our series.
CT data were acquired first, with the following parameters: tube rotation time, 0.5 s per revolution; 140 kV; 80 mA; 22.5 mm per rotation; slice pitch, 6; and acquisition time, 22.5 s for a scan length of 867 mm. Subsequently, PET emission data were acquired in 2-dimensional mode. Emission counts were collected during 4 min per table position, and adjacent fields of view shared 1 overlapping slice. Matched CT and PET image were reconstructed with a field of view of 500 mm and a 4.25-mm slice thickness. An iterative reconstruction and CT-based attenuation correction were used for the PET images (15). For viewing the images, the PET and CT datasets were transferred to an independent, personal computer-based computer workstation by DICOM (Digital Imaging and Communications in Medicine) transfer. All viewing of coregistered images was performed with dedicated software (eNTEGRA; General Electric).
To increase image quality and to suppress myocardial glucose utilization, patients were asked to fast for at least 4 h before the PET/CT examination. At the outset, patients received an intravenous injection of 300–400 MBq of 18F-FDG and rested for 50 min for the uptake of 18F-FDG to occur. 18F-FDG was produced in house by using a 17.8-MeV cyclotron (PET Trace 2000; General Electric) and an automated FDG synthesis module (PET Tracer Synthesizer; General Electric Nuclear Interface). Before PET, patients were encouraged to void to minimize activity in the bladder due to renal excretion of 18F-FDG.
Evaluation of PET/CT Images
Pathologic 18F-FDG accumulation was identified either by tracer uptake that exceeded that of the normal hepatic parenchyma but was clearly inferior to that of the cerebral cortex (moderate uptake) or was comparable or more intense than that of the cerebral cortex (strong uptake). All PET/CT examinations were interpreted by at least 1 board-certified nuclear physician and 1 board-certified radiologist. Two board-certified nuclear physicians reevaluated the selected cases in consensus to ascertain the localization, the degree of 18F-FDG uptake, as well as the pattern (focal, segmental, or diffuse) of the incidental 18F-FDG accumulation in the GIT. Proximal large bowel lesions were defined as those located proximal to the sigmoid colon (16). In the present investigation, we decided to include only patients with incidental 18F-FDG accumulation that correlates with abnormal soft-tissue density or wall thickening on the native CT.
This approach was chosen since nonspecific, primarily nonfocal, 18F-FDG accumulation, which may occur incidentally in a considerable number of patients (17), has been shown to carry an unacceptable high rate of false-positive results or irrelevant pathologic value in most instances (e.g., low-grade colonic inflammation, hypertrophied lymphoid follicles of the ascending colon, and reflux esophagitis). Eligibility criteria for mural thickening included an 8-mm cutoff for the normal rectal wall thickness and 5 mm for the rest of the GIT according to Cai et al. (18).
Standard of Reference
The final diagnosis of incidental 18F-FDG PET/CT findings was made on the basis of correlative endoscopic examinations in 69 patients. In 60 of these patients, additional histology of the biopsied lesion was available. In 9 patients of the 69 patients with incidental 18F-FDG accumulations in the GIT, no biopsy was performed because of normal findings on endoscopy.
Statistical Analysis
We performed statistical data analysis using the Fisher exact test to summarize our findings. The primary aim of this statistical analysis was to determine whether there is a special 18F-FDG uptake pattern that may predict the existence of an underlying relevant pathologic finding. For that purpose, we decided to compare the outcome of focally increased 18F-FDG uptake (group I) with that of segmentally and diffusely increased 18F-FDG uptake patterns (group II). P < 0.05 was considered significant.
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RESULTS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONCONCLUSIONREFERENCES |
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Two patients with moderately differentiated adenocarcinoma of the rectosigmoid colon revealed histopathologic evidence of highly dysplastic tubullovillous adenomas within their resected tumor materials (Fig. 1). Based on our PET/CT findings, 8 of 13 (62%) patients with colorectal (n = 6) and esophageal (n = 2) cancers could be scheduled to undergo curative surgical resection. The remaining 5 patients obtained palliative chemotherapy (n = 4) and combined radiochemotherapy (n = 1) because of their advanced tumor burden.
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Three patients, with recent intake of ciprofloxacin, demonstrated segmentally increased strong 18F-FDG uptake. In 1 of these 3 patients, Clostridium difficile was cultivated in the stool probes; hence, the diagnosis of a pseudomembranous colitis was made (Fig. 4). In 2 patients, acute diverticulitis of the sigmoid colon with focally increased strong 18F-FDG uptake was diagnosed on PET/CT and colonoscopy findings. On the corresponding CT images, typical CT features in the form of wall thickening and inflammatory changes in the adjacent pericolic fat were present.
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Miscellaneous Lesions
Six patients were identified with miscellaneous 18F-FDG PET/CT incidental findings of the GIT. The distribution of these lesions that showed focally increased 18F-FDG uptake was as follows: Two patients were harboring hemorrhoids with no signs of infection or inflammation. One had moderate and the other strong 18F-FDG uptake. In another 3 patients with strong (n = 2) and moderate (n = 1) 18F-FDG uptake, the diagnosis of a hyperplastic mucosal polyp was confirmed. These 3 polyps were located in the ascending colon, sigmoid colon, and the anal canal, respectively. The remaining patient revealed focally increased moderate 18F-FDG uptake in the esophagus. Endoscopic and histopathologic examinations identified glycogen acanthosis of the esophageal epithelium.
Discordant Findings
In 9 (13%) patients, pathologic 18F-FDG accumulation that correlated with abnormal soft-tissue density on the native CT did not correlate with any pathologic findings on endoscopy. In these patients, no biopsy was performed. Additionally, 7 small-sized, low-grade adenomas (range, 0.3–1.0 cm) were incidentally detected by colonoscopy in 5 patients in whom PET/CT and endoscopy already detected adenomas in another localization. Five of them displayed tubular and 2 displayed tubulovillous histology. These small adenomas did not show any 18F-FDG accumulation, even after reviewing the PET/CT data retrospectively.
Impact on Management
Besides the 27 patients with advanced colonic adenomas, who were certainly protected from potential malignant progression by virtue of PET/CT-guided polypectomy, the detection of incidental 18F-FDG PET/CT findings had a relevant impact on the clinical management of another 20 patients that were distributed as follows: The early detection of carcinoma in 13 patients lead to a curative resection in 8 of them (6 patients with occult colorectal and 2 patients with esophageal carcinomas). In 5 patients, the extent of the known primary carcinoma did not justify a resection of the newly diagnosed secondary carcinoma. These patients were treated by palliative chemotherapy (n = 4) and combined radiochemotherapy (n = 1). Furthermore, 2 patients with Barrett’s esophagus and intestinal metaplasia of the gastric mucosa were considered for close surveillance. In the group with inflammatory lesions, the detection of Clostridium difficile in 1 patient led to an appropriate antibiotic treatment.
The 2 patients with acute diverticulitis were also treated successfully with antibiotics. Four patients with colitis received either conservative therapy management with follow-up colonoscopy (n = 3) or an immunosuppressive therapy regimen (n = 1). The anal fissure, the anal ulcer, and the hemorrhoids were treated surgically. Thus, overall, the GIT findings resulted in changes in the clinical management in 20 (28%) of 69 patients.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONCONCLUSIONREFERENCES |
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In patients with multiple primary tumors, early detection of the second primary tumor has been claimed to improve the overall outcome (20). Based on our PET/CT findings, 8 of 13 (62%) patients with GIT cancers were eligible for curative surgical resection, whereas the primary tumor stage in the remaining 5 patients was such that they were only eligible for palliative chemotherapy (n = 4) and combined radiochemotherapy (n = 1).
In accordance with the developmental sequence from adenoma to carcinoma (22), 2 patients with newly diagnosed rectosigmoid cancers had histopathologic features consistent with moderately differentiated adenocarcinoma in a highly dysplastic tubulovillous adenoma (Fig. 1). Continuous efforts have been devoted to identify special adenoma characteristics that may predict outcome. According to the recent literature, there is unanimous agreement that, adenomas with a size > 1.0 cm, with tubulovillous or villous histology, or with high-grade dysplasia, invariably carry a high likelihood of malignant transformation (19). Based on these criteria, the detection of 27 advanced adenomas would have been missed, or at least postponed, if colonoscopy and excisional biopsy were not triggered by the incidental 18F-FDG PET/CT findings in our series.
Of note, dysplastic changes were observed in all of these incidentally detected adenomas (high grade, n = 7; low grade, n = 20). Using immunohistochemistry, 2 recent studies have shown that the proliferative rate of colonic adenomas correlates positively with the degree of dysplasia in a stepwise fashion (23,24). Interestingly, no statistically significant difference was observed between the proliferation index of colorectal carcinoma and highly dysplastic adenomas (24). Given the fact that most 18F-FDG-avid tumors are highly proliferating (25,26), it is obvious why 18F-FDG PET was capable of detecting these advanced adenomas.
The occurrence of 19 (70%) of 27 advanced adenomas among patients with aerodigestive tract tumors strengthens our observation about the propensity of a second primary GIT tumor in subjects with a known head and neck, lung, and gastrointestinal cancer.
Twenty (74%) of the successfully detected advanced adenomas in our series (n = 27) originated from or were distal to the sigmoid colon, which is also concordant with the literature (27). Detecting the 2 other precancerous lesions (Barrett’s esophagus and intestinal metaplasia of the gastric mucosa) has also had obvious prognostic significance (Fig. 3), as these lesions are well known to be able to transform to differentiated adenocarcinoma if left without interference (28,29).
In patients with suspected cancer, infectious or inflammatory conditions are a major source of false-positive results on 18F-FDG PET. However, correlation of the PET data with those obtained by CT or MRI may allow more precise differentiation between malignant and benign lesions. In the present study, 12 (17%) of 69 patients had incidental inflammatory or infectious findings of the GIT. Of note, 4 patients were harboring pathologies prone to peritonitis: necrotizing colitis (n = 1), pseudomembranous colitis (n = 1), and diverticultitis (n = 2). Given the known morbidity and mortality that is associated with these entities, potential complications may have been averted due to their early identification by PET/CT.
Few studies have discussed the role of 18F-FDG PET in the diagnosis of enterocolitis as well as necrotizing and pseudomembranous colitis. Despite the small number of patients in these reports, it has been concluded that PET may be a useful noninvasive tool in identifying active bowel inflammation, even in the face of nondiagnostic structural imaging modalities and colonoscopy (3,4,30).
Three hyperplastic colonic polyps, 2 anorectal hemorrhoids, and 1 glycogenic acanthosis of the esophagus without signs of infection were incidentally detected in 6 patients on 18F-FDG PET/CT. 18F-FDG accumulation can be related to the proliferative activity in both hyperplastic polyps and esophageal glycogenic acanthosis (31,32). However, no obvious reason other than the existence of minimal thrombotic changes can explain 18F-FDG accumulation in the 2 patients with uncomplicated hemorrhoids (33).
When the focal 18F-FDG uptake pattern was compared with the segmental and diffuse pattern in the whole GIT, 90% of the cancerous and precancerous findings and 50% of the benign findings (inflammatory and miscellaneous lesions) were characterized by focally increased 18F-FDG uptake (P = 0.001). This may suggest that focally increased 18F-FDG uptake seems to be predictive of relevant pathologic findings on colonoscopy—primarily precancerous or cancerous lesions.
Discordant findings between 18F-FDG PET/CT and ensuing colonoscopy were observed in 9 (13%) patients. Based on our inclusion criteria, PET/CT suggested the existence of colonic pathology in these 9 patients. The origin of the increased 18F-FDG uptake could not be identified, but possible explanations are lesions below the mucosal surface inspected with the colonoscope or shedding of 18F-FDG-containing superficial mucosal cells into the stool. Additionally, 7 small colonic low-grade adenomas (0.3–1 cm) were not identified by PET/CT. Partial-volume effects that underestimate the 18F-FDG activity of small-sized lesions or activity smearing by bowel motion are the most likely explanations (34).
A limitation of this study is that 29 of 98 patients (30%) with incidental findings were not subject to further endoscopic examination. However, we were interested in evaluating the clinical significance of these incidental 18F-FDG PET/CT findings rather than to determine their prevalence in a typical population referred for PET. An additional limitation is that missing potentially non-18F-FDG-avid GIT lesions that might have had minor structural abnormalities on the native CT cannot be excluded since we did not apply either a standard bowel preparation regimen or intravenous contrast material as a part of standard protocol in the studied patient population.
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CONCLUSION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONCONCLUSIONREFERENCES |
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ACKNOWLEDGMENTS |
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FOOTNOTES |
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For correspondence contact: Katrin D.M. Stumpe, MD, Nuclear Medicine, Department of Medical Radiology, University Hospital of Zurich, CH-8091 Zurich, Switzerland.
E-mail: katrin.stumpe{at}usz.ch
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REFERENCES |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONCONCLUSIONREFERENCES |
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