We retrospectively studied 396 patients who underwent PET-CT scanning prior to gastrectomy to treat gastric cancer at Kosin Medical College Department of Surgery from 1 January 2009 to 31 December 2009. Among these 396 patients (278 men, 118 women; age range: 27 to 86; mean age: 59 years), 384 underwent radical subtotal or total gastrectomies, 4 underwent open and closure (O&C) and 8 cases had palliative surgery. One patient who had subtotal gastrectomy and another patient who had palliative surgery had got neoadjuvant therapy. Patients who had other treatment modalities such as endoscopic mucosal resection and endoscopic submucosal dissection would be enrolled in this study only after gastrectomies. TNM staging was done based on specimen pathology determined after surgery. TNM staging was based on the America Joint Committee on Cancer Staging Manual-Seventh Edition.

To determine the utility of PET-CT for gastric cancer staging, we assessed the relationship between T stage and fluorodeoxyglucose (FDG) uptake, the sensitivity and specificity for N staging, the sensitivity for pathologic classification, and the relationships among carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9) and FDG uptake. We used SPSS for Windows (ver. 17.0, SPSS Inc., Chicago, IL, USA) for statistical analysis of the data. We also evaluated the clinical courses of the 24 patients in whom FDG uptake in lesions other than the primary tumor was detected.

All patients fasted for at least six hours and were confirmed to have a serum glucose level less than 140 mg/dl before IV injection of FDG. Scanning was performed 60 minutes after FDG administration. Scans were acquired with a PET-CT system (CTI, Knoxville, TN, USA), which consisted of a full-ring positron emission tomography (PET) scanner and a dual-detector-row spiral CT scanner (Somatom Emotion Duo, Biograph, Erlangen, Germany). The CT scan was done from the head to the pelvic floor according to a standard protocol at 130 kVp and 30 mA with a tube rotation time of 0.8 seconds per rotation, a pitch of 6, and a 5 mm section thickness to match the PET section thickness. Immediately after the non-enhanced CT scan, PET was performed in the identical transverse field of view. PET data sets were obtained via interactive reconstruction using an ordered subset expectation maximization algorithm and by application of segmented attenuation correction (two interactions, 28 subsets) to the CT data. Co-registered scans were displayed with the software, which enabled image fusion and analysis.

PET-CT scans were interpreted by one nuclear medicine physician, and he defined a positive primary lesion as an abnormally higher FDG uptake compared to the uptake of the surrounding tissues. Positive lymph node metastases were also defined as abnormal FDG uptake in a lymph node higher than normal tissues. Positivity for double primary cancer or distant metastases were defined as significantly higher FDG uptake in the detected lesions compared to the uptake of the surrounding tissue

According to the endoscopic findings, there were 237 (59.8%) patients who had early gastric cancer and 159 (40.2%) who had advanced gastric cancer. The endoscopic findings of the advanced gastric cancers revealed 8, 88, 50 and 13 patients with Borrmann type I, II, III and IV, respectively. The primary lesion size was less than 1 cm in 54 patients, between 1 cm and 3 cm in 163 patients, and larger than 3 cm in 179 patients.

World Health Organization (WHO) and Lauren pathologic classifications were used in this study. The WHO system classifies tumors into the following sub-classes: papillary adenocarcinoma, well differentiated tubular adenocarcinoma (TA), moderately differentiated TA, poorly differentiated TA, mucinous adenocarcinoma and signet ring cell type. It also classifies tumors based on pathologic differentiation such as "differentiated adenocarcinoma" and "undifferentiated adenocarcinoma" (Table 1).

Endoscopic findings indicated early gastric cancer in 237 of the 396 patients and advanced gastric cancer in the remaining 159. PET-CT findings were positive in 49 of the 237 early gastric cancer patients (20.7%) and in 118 of the advanced gastric cancer patients (74.2%), indicating that PET-CT is more sensitive for detecting advanced gastric cancer. We could not find considerable differences between those results and results of T-staging according to pathologic findings. Among the advanced gastric cancers, the sensitivities of positive uptake on PET-CT were 75%, 73.9%, 76% and 69.2% for Borrmann type I, II, III and IV, respectively, and P-value was 0.967 (Table 2). We found that the sensitivity of PET-CT for T staging was 11.9% for T1a (13/109), 27.5% for T1b (30/109), 55.4% for T2 (31/56), 71.4% for T3 (35/49), 76.5% for T4a (39/51) and 88.9% for T4b (16/18), suggesting that the sensitivity of this modality increases with T stage and it had <0.001 of P-value (Table 2). Sensitivities in terms of primary lesion size were 18.5% for lesions less than 1 cm (10/54), 23.9% for those 1~3 cm (39/163) and 65.9% for lesions larger than 3 cm (118/179) (Table 2). P-value was <0.001. These finding indicate that the sensitivity of PET-CT is influenced by the T stage and the size of the primary lesion. Thus, we assessed the statistical relationship between the T stage and maximum standardized uptake value (SUVmax) to define the T stage. We found that as the T stage increased to T4b, SUVmax also increased and the value of R² was 0.05 (Fig. 1). We determined the relationship between the WHO pathologic classification and uptake on PET-CT and found that 81 of 199 cases were the differentiated type and 79 of 187 were the undifferentiated type (Table 2). In terms of the Lauren pathologic classification, the sensitivity of PET-CT for detecting the intestinal type was 47.1% (114/242), 27.9% (29/103) for the diffuse type, 39.4% (13/33) for the mixed type and 64.7% (11/17) for the unknown type, which included O&C cases. The P-value was 0.002 (Table 2).

We evaluated the sensitivity of PET-CT for detecting primary lesion uptake according to the N stage and found that 25% of cases were node negative and 75% were node positive. It is thought that most of the node positive cases would be advanced gastric cancer. To understand the utility of PET-CT for N staging, the sensitivity of this modality for detecting the uptake of metastatic nodes was assessed and the results were 5.2% for N0 (14/266) and 30.7% for N1-N3b, Nx (40/130). In cases of O&C and palliation, they were included in Nx staging. The sensitivity for overall node metastasis was 30.7%, the specificity was 94.7%, the positive predictive value was 74.1% and the negative predictive value was 73.7% (Table 3).

Two of the most used gastric cancer tumor markers are CEA and CA 19-9 and both had a positive correlation with SUVmax. R² values were 0.001 and 0.005, respectively (Fig. 2).

Uptake in lesions other than the primary tumor was noted in 24 of the 396 patients. These 24 patients were studied in detail and in order to determine the value of PET-CT for M staging. There were seven cases that showed colon uptake and all had previously undergone routine pre-operative colonoscopy. One patient was determined to have colon cancer based on histologic analysis of the polypectomy specimen, and the patient subsequently underwent a combined operation. Two of the other six cases were determined to be benign polyps after polypectomy. The four remaining cases showed normal findings on colonoscopy and they are still being followed-up.

Five of the twenty-four cases showed liver uptake, and all of these patients underwent a routine pre-operative abdominal CT and liver ultrasonography and also both of them had positive findings. Two cases underwent hepatectomy with gastrectomy, and hepatocellular carcinoma was diagnosed in one while a metastatic nodule was found in the other. Two cases underwent palliative gastrectomy because of liver lesions and one patient had a palliative bypass gastrojejunostomy for cancer peritonei.

There were four cases of uptake in the lungs and all underwent a high resolution chest CT. One case was strongly suspected to be a metastatic nodule and the patient underwent palliative gastrectomy after neoadjuvant chemotherapy. One case had an undetermined pulmonary nodule and therefore underwent bronchoscopy and endoscopic bronchial ultrasonographic biopsy and the nodule was confirmed to be benign. Others were suspected of having latent tuberculosis and therefore underwent gastrectomy with subsequent observation.

Thyroid uptake was noted in two cases, and cancer was already suspected in one of the two patients was due to the presence of a large goiter. The patient underwent fine needle aspiration biopsy, which led to a diagnosis of follicular neoplasm. The patient then underwent a combined thyroidectomy and the neoplasm was found to be follicular carcinoma, which required continued observation and care. The other case underwent thyroid ultrasonography and the result was an indeterminate nodule. This patient underwent fine needle aspiration biopsy, which revealed it to be a benign nodule.

Two cases with gallbladder uptake received combined cholecystectomy and both patients had diagnosis of cholecystitis. Bone uptake was observed in two cases and both patients had a bone scan. One case was strongly suspected to be bone metastasis, so the patient underwent palliative gastrectomy with chemotherapy, while the other case was suspected to be degenerative change. One case showed abdominal wall uptake and was subsequently assessed with CT. During the laparoscopic distal gastrectomy, the suspect lesion was observed, but appeared normal. Thus, the patient was followed-up with PET-CT 6 months later post-operatively and the lesion was found to have disappeared on PET-CT.

One case with a breast uptake underwent breast ultrasonography and mammography, and the result was a category 2 lesion, which was followed up. There was one case that showed cerebellar uptake. The patient's history was taken and transcranial Doppler ultrasonography and 3D angio CT were performed. The uptake was determined to be an old cerebellar infarction.

To summarize, abnormal uptake on PET-CT was observed in 24 of 396 patients for M staging and nine cases were found to have malignant lesions, including primary and metastatic lesions. In 12 cases the lesions were found only on PET-CT without routine preoperative studies. As a result, malignancies were detected in two cases only on PET-CT (Fig. 3).