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PET/CT Detection of Unexpected Gastrointestinal Foci of ¹⁸F-FDG Uptake: Incidence, Localization Patterns, and Clinical Significance

¹ Department of Nuclear Medicine, Rambam Medical Center, Haifa, Israel
² B. Rappaport School of Medicine, Technion, Israel
³ Department of Diagnostic Radiology, Rambam Medical Center, Haifa, Israel

	ABSTRACT

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION CONCLUSION REFERENCES

 
Precise PET/CT localization of focal ¹⁸F-FDG uptake in the gastrointestinal tract (GIT) may exclude malignancy in sites of physiologic activity but may also induce false-negative reports for malignant or premalignant lesions. The purpose of the present study was to retrospectively evaluate the nature and significance of unexpected focal ¹⁸F-FDG uptake localized by PET/CT within the GIT. Methods: The files of 4,390 patients referred for ¹⁸F-FDG PET/CT were retrospectively reviewed. The incidence of studies showing unexpected focal uptake of ¹⁸F-FDG localized by PET/CT to the GIT was determined. The position of these foci along the GIT and their intensity were recorded. The etiology of the findings was confirmed histologically or by long-term follow-up. Results: Unexpected focal ¹⁸F-FDG uptake in the GIT was found in 58 patients (1.3%). Follow-up data were available for 34 of these patients, including 4 with sites in the stomach, 2 in the small bowel, and 28 in the colon. GIT-related disease was confirmed in 24 patients (71%). There were 11 malignant tumors, 9 premalignant lesions, and 4 benign processes including 2 benign polyps, 1 case of active gastritis, and 1 abscess of the sigmoid. Ten patients (29%) had no further evidence of GIT abnormality, and the suggestive sites were considered to be physiologic uptake. Maximal standardized uptake value was 17.3 ± 10.2 in malignant lesions, 14.0 ± 10.5 in premalignant lesions, 18.0 ± 12.1 in benign lesions, and 11.1 ± 7.4 in foci of physiologic ¹⁸F-FDG uptake in the GIT, with no statistically significant difference among the 4 subgroups. Conclusion: Incidental focal ¹⁸F-FDG uptake localized by PET/CT within the GIT is of clinical significance in most patients. These findings should be followed up with appropriate invasive procedures guided by hybrid imaging results.

Key Words: gastrointestinal tract foci • ¹⁸F-FDG • PET/CT • oncology • pitfalls

	INTRODUCTION

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PET using ¹⁸F-FDG has successfully been implemented in the evaluation of malignant tumors. Diagnosis of cancer is based on the ability of ¹⁸F-FDG PET to detect foci of tumors with increased glycolysis (1,2). Increased ¹⁸F-FDG uptake, however, besides being present in malignant lesions, is present in benign, inflammatory, or granulomatous processes and in sites of normal, physiologic tracer biodistribution (3,4). These physiologic or benign sites of ¹⁸F-FDG uptake may be falsely attributed to a cancerous etiology, and increased tracer activity in malignant lesions may be erroneously interpreted as unrelated to cancer (2–6). ¹⁸F-FDG is excreted in part through the gastrointestinal tract (GIT), with uptake in the distal esophagus, stomach, small intestine, and large intestine representing normal patterns of tracer distribution (3,4). Diffuse increased ¹⁸F-FDG uptake in the GIT can be defined as physiologic and unrelated to the malignant process with relatively high certainty. A focal, well-circumscribed intraabdominal area of increased ¹⁸F-FDG uptake may, however, be interpreted as equivocal or suggestive of malignancy with an unclear location (4,5).

Hybrid PET/CT provides anatomic landmarks for better characterization of increased ¹⁸F-FDG uptake (7). Initial literature reports have shown that the precise localization of hypermetabolic lesions by PET/CT may change the definition of focal intraabdominal ¹⁸F-FDG uptake from an indeterminate or equivocal to a benign etiology and therefore improve the diagnostic accuracy of PET (7,8). This study was initiated by a series of cases in which focal intraabdominal ¹⁸F-FDG uptake that had been localized by PET/CT to the GIT, which had no previously known morphologic lesions, was proven on follow-up to be of malignant or premalignant etiology. The purpose of the present study was to evaluate the frequency of incidental focal sites of increased ¹⁸F-FDG uptake in the GIT and to assess the clinical significance of these unexpected findings.

	MATERIALS AND METHODS

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Patient Population
The files of 4,390 patients with known or suspected malignancy, who underwent whole-body ¹⁸F-FDG PET/CT during the period September 2001 to March 2004, were retrospectively reviewed. All patients gave written informed consent for the PET/CT study and for evaluation of their clinical records for follow-up.

This analysis included PET studies showing a single site of focally increased abdominal ¹⁸F-FDG uptake that was more intense than liver uptake and was localized by fused PET/CT to the GIT. The patients had no previous malignant involvement and no clinical or imaging suspicion of abnormalities in the same areas. Fifty-eight patients met these inclusion criteria, and they represented the group for calculating the incidence of unexpected focal ¹⁸F-FDG uptake in the GIT on whole-body PET.

Of the 58 studies showing incidental focally increased ¹⁸F-FDG uptake in the GIT, follow-up data were available for 34 patients, who represented the study group for further assessment of the clinical significance of these findings. There were 22 men and 12 women, with a mean age of 66 y (range, 27–88 y). The primary malignant tumors were colon cancer (n = 9), lymphoma (n = 7), lung cancer (n = 6), and metastatic cancer of unknown origin (n = 2). One patient each had sarcoma; malignant histiocytoma; and esophageal, gastric, or breast cancer. Five additional patients were evaluated for further characterization of single pulmonary nodules. PET/CT was performed on 14 patients assessed for diagnosis or staging, 5 patients assessed at restaging after initial treatment, and 15 patients assessed as part of routine follow-up or because recurrence was suspected.

Imaging Protocol
Patients were instructed to fast, except for glucose-free oral hydration, for 4–6 h before the injection of 370–555 MBq (10–15 mCi) of ¹⁸F-FDG. After the tracer administration, patients remained lying comfortably and then voided immediately before PET/CT. The urinary bladder was not catheterized, and oral muscle relaxants were not administered. Whole-body PET and unenhanced CT images were acquired consecutively, 60–90 min after the injection, using a PET/CT system (Discovery LS; General Electric Medical Systems) combining a dedicated, full-ring PET scanner with bismuth germanate crystals and a third-generation multislice spiral CT scanner. The PET and CT devices were mechanically aligned back to back and shared a common table. The CT and PET images were registered using their shared positional information about the table and the patient.

Data obtained from CT were used for low-noise attenuation correction of the PET emission data and for fusion with attenuation-corrected PET images. PET images were reconstructed iteratively using ordered-subset expectation maximization software. PET, CT, and fused whole-body images displayed in axial, coronal, and sagittal planes were available for review. The PET data were also displayed in a rotating maximum-intensity projection.

Interpretation and Analysis of PET/CT Images
PET studies showing single, well-circumscribed foci of increased abdominopelvic ¹⁸F-FDG uptake localized by PET/CT images to the GIT, including the esophagus, stomach, small intestine, or colon, were reviewed. The colon was further divided into ascending colon, descending colon, sigmoid, and rectum. The intensity of the ¹⁸F-FDG uptake was measured as the maximal standardized value uptake of ¹⁸F-FDG (SUV_max), using the software provided by the workstation manufacturer.

After PET/CT, 30 of the 34 patients underwent additional procedures for evaluation of the area of focally increased ¹⁸F-FDG uptake. These included surgery in 8 patients, colonoscopy with biopsy in 11 patients, gastroscopy with biopsy in 4 patients, and ultrasound-guided fine-needle aspiration in 1 patient. Six patients underwent colonoscopy that revealed no abnormal findings, and therefore no histologic specimens were obtained. Four patients had only clinical follow-up, for periods ranging from 12 to 31 mo.

Foci of increased tracer uptake in the GIT in patients with negative endoscopic findings, and with no further evidence of disease during a follow-up period of at least 12 mo, were considered to represent sites of physiologic ¹⁸F-FDG activity.

The incidence of unexpected focally increased ¹⁸F-FDG uptake in the GIT was calculated. The locations of suggestive foci were recorded. The intensity of the uptake was measured for the whole study population and compared among subgroups defined by histologic results and clinical follow-up. Differences in SUV_max among the 4 subgroups were assessed for statistical significance using 1-way ANOVA.

	RESULTS

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Focally increased ¹⁸F-FDG uptake localized by PET/CT to the GIT was found in 58 of the 4,390 patients (1.3%). Of the 34 patients with confirmatory follow-up data, the focal ¹⁸F-FDG uptake was in the stomach in 4 patients, the small intestines in 2, and the colon in 28. Of the 28 suggestive colonic sites, 13 were in the ascending colon, 6 in the descending colon, 7 in the sigmoid, and 2 in the rectum (Table 1).

View larger version (76K): [in this window] [in a new window]   FIGURE 1. Focal 18F-FDG uptake in 57-y-old woman who had undergone total gastrectomy for stomach cancer and was being evaluated for fatigue, abdominal pain, frequent vomiting, equivocal endoscopic findings at level of anastomosis, and negative findings on whole-body CT. (A) From left to right, coronal, sagittal, and transaxial PET slices show focus of increased 18F-FDG uptake (arrows) in left lower abdomen. (B) Area of increased uptake (arrows) was localized by PET/CT (left panel) to small bowel, as seen on corresponding CT image (right panel). PET/CT-guided surgery revealed small-bowel metastasis originating from primary gastric cancer. No abnormal 18F-FDG uptake was seen in region of anastomosis, and there was no further evidence of disease in this area.

View larger version (85K): [in this window] [in a new window]   FIGURE 2. Focal 18F-FDG uptake in 64-y-old woman who was being evaluated for staging of aggressive non-Hodgkin’s lymphoma. (A) From left to right, coronal, sagittal, and transaxial PET slices show focus of increased 18F-FDG uptake (arrows) in left pelvis. Coronal and sagittal PET images show additional areas of abnormal 18F-FDG uptake in mediastinum and left upper abdomen (open arrows), consistent with sites of active lymphoma. (B) Pelvic area of increased uptake (arrows) was localized by PET/CT (left panel) to sigmoid, as seen on corresponding CT image (right panel). Villous adenoma was diagnosed from biopsy sample taken during colonoscopy.

View larger version (79K): [in this window] [in a new window]   FIGURE 3. Focal 18F-FDG uptake in 70-y-old woman with low-grade non-Hodgkin’s lymphoma who was undergoing routine follow-up examination. (A) Coronal, sagittal, and transaxial PET slices show focus of increased 18F-FDG uptake (arrows) in right upper abdomen. (B) Area of increased uptake (arrows) was localized by PET/CT (left panel) to ascending colon, as seen on corresponding CT image (right panel). Colonoscopy had negative findings, and patient showed no evidence of disease after 16 mo of follow-up. Focus of increased 18F-FDG uptake was considered to represent physiologic bowel activity.

The final histologic diagnosis, location, and intensity of focal ¹⁸F-FDG uptake in the GIT are summarized in Tables 1 and 2.

	DISCUSSION

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION CONCLUSION REFERENCES

 
Incidental foci of abnormal ¹⁸F-FDG uptake, precisely localized by PET/CT to the GIT, were found in 1.3% of the present study population. Of these unexpected suggestive sites, follow-up data showed that 71% were caused by GIT-related pathology, with 59% representing malignant or premalignant lesions.

Physiologic ¹⁸F-FDG uptake of variable intensity and localization patterns within the GIT has previously been described. Focal tracer uptake is frequently seen at the gastroesophageal junction; moderate uptake, in the stomach; low-intensity uptake, in the small bowel; and diffuse or focal uptake, in the colon (3). This physiologic tracer activity in the GIT has been attributed to uptake by smooth muscles (mainly in the bowel), swallowed secretions, or excretion and intraluminal concentration of ¹⁸F-FDG (9,10).

PET using ¹⁸F-FDG is more accurate than CT or other conventional imaging modalities for diagnosis of previously unknown recurrent or metastatic malignant foci (11,12). Focal colonic ¹⁸F-FDG uptake has a high, 70%–80%, probability of showing corresponding abnormal histopathologic findings (11–13). Despite possible false-positive results, colonoscopy has therefore been recommended as the next diagnostic step for further evaluation of these findings (14,15). The present study found a slightly lower incidence, 64%, of clinically significant lesions in the colon, with a total of 71% throughout the whole GIT.

Although previous studies have evaluated the etiology of incidental ¹⁸F-FDG PET findings in the colon (13,15), the clinical significance of abnormal foci in other parts of the GIT has not, to our knowledge, previously been addressed. In the present study, 6 of the 34 suggestive foci (18%) were in the stomach or small bowel, with all but 1 of these lesions proving malignant on further evaluation (Fig. 1).

Metastases have previously been considered to represent an unusual etiology for unexpected single sites of ¹⁸F-FDG uptake in the GIT (11). In the present study population, 12% of incidental foci represented metastatic lesions, in addition to the 26% that were premalignant lesions and the 21% that were primary malignancies (Figs. 1 and 2).

Semiquantitative SUV measurements have been suggested as a tool to differentiate between potential etiologies of ¹⁸F-FDG foci in the GIT (16). In the current series, a similar but wide range of ¹⁸F-FDG uptake values was found in the different subgroups.

PET/CT has been advocated as a useful novel imaging tool leading to a decrease in the number of false-positive and false-negative PET findings in cancer patients (5,7,11). Despite this increase in confidence and decrease in the number of suggestive or equivocal lesions, the precise localization of increased ¹⁸F-FDG foci using PET/CT cannot, at present, solve the diagnostic dilemma of abnormal tracer uptake in the GIT. Single sites of focally increased ¹⁸F-FDG uptake, precisely localized by hybrid images to the GIT, warrant further evaluation using more invasive diagnostic procedures. Tissue sampling appears to be the only way to define the etiology and clinical significance of focal areas of ¹⁸F-FDG uptake in the GIT in individual patients. In this clinical setting, however, PET/CT can play an important role in guiding further investigations, including biopsy or surgery, leading to a decrease in tissue-sampling errors and enhancing early, improved diagnosis and treatment.

	CONCLUSION

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION CONCLUSION REFERENCES

 
The results of the present study indicate the need for further assessment and PET/CT-guided tissue sampling in patients with unexpected single areas of focal abnormal ¹⁸F-FDG uptake in the GIT. Most of these incidental foci represent unexpected GIT-related abnormalities, such as second primary tumors, sites of unusual metastatic spread, or premalignant lesions.

	ACKNOWLEDGMENTS

 
This work was supported in part by a research grant from the Israeli Cancer Association. The authors acknowledge the many useful suggestions of Dr. Anthony J. Parker and Judy Buchanan.

	FOOTNOTES

 
Received Nov. 2, 2004; revision accepted Dec. 15, 2004.

For correspondence or reprints contact: Ora Israel, MD, Department of Nuclear Medicine, Rambam Medical Center, Haifa 35254, Israel.

E-mail: o_israel{at}rambam.health.gov.il

	REFERENCES

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION CONCLUSION REFERENCES

 

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