Ryusuke Takebayashi

Detection of gastric cancer using 18F-FLT PET: comparison with 18F-FDG PET.

PurposeWe prospectively investigated the feasibility of 3′-deoxy-3′-18F-fluorothymidine (FLT) positron emission tomography (PET) for the detection of gastric cancer, in comparison with 2-deoxy-2-18F-fluoro-d-glucose (FDG) PET, and determined the degree of correlation between the two radiotracers and proliferative activity as indicated by Ki-67 index.MethodsA total of 21 patients with newly diagnosed advanced gastric cancer were examined with FLT PET and FDG PET. Tumour lesions were identified as areas of focally increased uptake, exceeding that of surrounding normal tissue. For semiquantitative analysis, the maximal standardized uptake value (SUV) was calculated.ResultsFor detection of advanced gastric cancer, the sensitivities of FLT PET and FDG PET were 95.2% and 95.0%, respectively. The mean (±SD) SUV for FLT (7.0 ± 3.3) was significantly lower than that for FDG (9.4 ± 6.3 p < 0.05). The mean FLT SUV and FDG SUV in nonintestinal tumours were higher than in intestinal tumours, although the difference was not statistically significant. The mean (±SD) FLT SUV in poorly differentiated tumours (8.5 ± 3.5) was significantly higher than that in well and moderately differentiated tumours (5.3 ± 2.1; p < 0.04). The mean FDG SUV in poorly differentiated tumours was higher than in well and moderately differentiated tumours, although the difference was not statistically significant. There was no significant correlation between Ki-67 index and either FLT SUV or FDG SUV.ConclusionFLT PET showed as high a sensitivity as FDG PET for the detection of gastric cancer, although uptake of FLT in gastric cancer was significantly lower than that of FDG.

Impact of 18-fluorodeoxyglucose positron emission tomography on the management of pancreatic cancer.

BackgroundWe compared the usefulness of positron emission tomography with the glucose analogue 2-deoxy-2-[18F]-fluoro-d-glucose (FDG-PET) and multidetector-row computed tomography (MD-CT) in diagnosing pancreatic cancer and in determining the patients’ suitability for surgery.MethodsWe reviewed the clinical FDG-PET data of 103 consecutive pancreatic cancer patients between July 2004 and March 2009.ResultsThe detection rates of pancreatic cancer by MD-CT (89%) and FDG-PET (91%) were similar. From the MD-CT findings, 38 patients were judged as operable, and 65, inoperable. Among the inoperable patients, noncurative factors (metastasis to the liver, peritoneum, remote lymph nodes, bones, and other organs and major arterial invasion) were detected by MD-CT and/or FDG-PET. Detection rates of liver metastasis and arterial invasion by FDG-PET were significantly inferior to those of MD-CT (neither was detected by FDG-PET alone). Remote lymph nodes and bone metastasis were detected in 20 lesions by FDG-PET alone; however, MD-CT indicated other noncurative factors in these patients. All 65 patients could be diagnosed as inoperable without FDG-PET.ConclusionsFDG-PET is not a suitable imaging modality for either diagnosis or preoperative treatment in pancreatic cancer patients. Since it is expensive, FDG-PET as a routine diagnostic tool in pancreatic cancer patients must be used with caution.

Detection of colorectal cancer using 18F-FLT PET: comparison with 18F-FDG PET

ObjectiveWe investigated the feasibility of 3′-deoxy-3′-18F-fluorothymidine (FLT) positron emission tomography (PET) for the detection of colorectal cancer, in comparison with 2-deoxy-2-18F-fluoro-D-glucose (FDG) PET, and investigated correlation of the two radiotracers used with proliferative activity as indicated by Ki-67 index. MethodsA total of 26 patients with newly diagnosed colorectal cancer were examined with FLT PET and FDG PET. Tumor lesions were identified as areas of focally increased uptake, exceeding that of surrounding normal tissue. For semiquantitative analysis, the maximal standardized uptake value (SUV) was calculated. ResultsIn all 26 patients, colorectal cancers were detected by both FLT PET and FDG PET. The mean (±SD) values of FLT SUV in colon cancer (5.4±2.4) and in rectal cancer (5.6±1.3) were significantly lower than the corresponding values of FDG SUV (12.4±6.3 and 12.5±4.7, respectively) (P<0.003). There was no significant correlation between Ki-67 index and either FLT SUV or FDG SUV. ConclusionAlthough uptake of FLT was found to be significantly lower than that of FDG, both FLT PET and FDG PET were able to detect colorectal cancers in all 26 patients. Neither of the two radiotracers used was correlated with proliferative activity.

Molecular Mechanism Underlying the Detection of Colorectal Cancer by 18F-2-Fluoro-2-Deoxy- d -Glucose Positron Emission Tomography

BackgroundBiological imaging by positron emission tomography (PET) using 18F-2-fluoro-2-deoxy-d-glucose (FDG) has been widely used clinically for the detection of primary tumors and for early prediction of response to chemotherapy. In this study, we examined the molecular mechanism underlying the detection of colorectal cancers by FDG-PET.Material and MethodsIn all, 37 patients with colorectal cancer were examined with FDG-PET, and the maximal standardized uptake value (SUV) was calculated. Using surgical tissue samples, we examined the expression levels of hypoxia-inducible factor alpha (HIF1α), a marker of tissue hypoxia; proliferative cellular nuclear antigen (PCNA), a marker of proliferation; and glucose transporter (GLUT)1 and hexokinase (HK)2, protein of glucose uptake by using reverse transcriptase-polymerase chain reaction.ResultsAll except two colorectal cancer lesions showed increased uptake of FDG. The mean SUV of FDG-PET was 12.0 ± 1.2 (±SEM). The mean mRNA expression levels of GLUT1 and HK2 were significantly higher in cancer tissues than in the surrounding normal mucosa. Moreover, to promote the upregulation of glucose uptake, the expressions of HIF1α and PCNA were induced to 2.6 and 3.3 times higher than that in the normal mucosa. However, the quantitative correlation analysis showed SUV was correlated with HIF1α expression but not with PCNA expression.ConclusionOur molecular-based analysis suggested that FDG accumulation due to induction of glucose uptake proteins might be associated with the hypoxic environment in tumors rather than the tumor growth. Therefore, for assessing the efficacy of chemotherapy using FDG-PET, we must keep in mind that SUV does not indicate the tumor growth directly.

18F)Fluorodeoxyglucose accumulation as a biological marker of hypoxic status but not glucose transport ability in gastric cancer

BackgroundThe use of [18F] 2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) for detection of gastric cancer is often debated because FDG uptake varies for each patient. The purpose of this study was to clarify the molecular mechanisms involved in FDG uptake.Material and methodsFifty patients with gastric cancer who underwent FDG-PET and gastrectomy were studied. Snap-frozen tumor specimens were collected and examined by real-time PCR for relationships between maximum standardized uptake value (SUV) and mRNA expression of the following genes: glucose transporter 1 (GLUT1), hexokinase 2 (HK2), hypoxia-inducible factor 1α (HIF1α), and proliferating cell nuclear antigen (PCNA).ResultsTumor size was the only clinicopathological parameter that significantly correlated with SUV. Transcripts for the genes evaluated were about three-fold higher in malignant specimens than in normal mucosa, although only HIF1α was significantly correlated with SUV. When divided into intestinal and non-intestinal tumors, there was a significant correlation between SUV and tumor size in intestinal tumors. Interestingly, the weak association between SUV and HIF1α expression in intestinal tumors was substantially stronger in non-intestinal tumors. No correlation was found between SUV and mRNA expression of other genes in intestinal or non-intestinal tumors.ConclusionSUV was correlated with HIF1α, but not PCNA, HK2, or GLUT1 expression. FDG accumulation could therefore represent tissue hypoxia rather than glucose transport activity for aggressive cancer growth.

Surgical approach for extrahepatic metastasis of HCC in the abdominal cavity.

BACKGROUND/AIMS Despite recent development of therapeutic strategies for intrahepatic lesions, standard guidelines for treatment of extrahepatic metastases of hepatocellular carcinoma have not been established. METHODOLOGY Surgical resection for intra-abdominal extrahepatic metastases of hepatocellular carcinoma was performed on 10 patients at our institution between 1992 and 2008. We retrospectively examined the clinicopathologic features and significance of a surgical approach in these patients. RESULTS Nine of the 10 patients received treatment for primary hepatocellular carcinoma before surgery for intra-abdominal extrahepatic metastasis. A simultaneous intrahepatic lesion was detected in half of the patients when the extrahepatic metastasis was resected. Extrahepatic recurrent organs included adrenal glands, lymph nodes, abdominal wall, stomach and diaphragm. The mean survival period after resection was 36.1 months. Two patients are still alive without further recurrence. One patient died of retroperitoneal recurrence and 7 died of intrahepatic recurrence or liver failure after resection. CONCLUSIONS With careful case selection, considering that not all extrahepatic metastases suggest systemic spread of hepatocellular carcinoma, surgical treatment for metastatic lesions in the abdominal cavity can provide a relatively good prognosis.

Operative management of solitary intra-abdominal recurrence of hepatocellular carcinoma

Although no statistically significant difference was identified by Gutierrez et al, the survival in high-volume centers did seem to be greater than in low-volume centers. It is possible that studies with a larger sample size and thus more power will identify a difference in survival in favor of children treated at high-volume centers. In conclusion, the conclusion of Gutierrez et al that survival for children with neuroblastoma or Wilms tumor is unrelated to hospital surgical volume is not supported by their study findings. Their study showed a nonsignificant improvement in survival for patients treated at high volume centers. More studies with adequate power are warranted to answer the question of whether pediatric cancer patients treated at high-volume centers have a better survival than children treated at low-volume centers.

Hepatobiliary and pancreatic: Isolated diaphragmatic metastasis from hepatocellular carcinoma

An 82-year-old man was referred to our hospital with a presumed metastasis on the liver surface. Thirty months previously, he had been treated with a segmental resection of the liver (segments VI and VII) for a solitary hepatocellular carcinoma, approximately 5 cm in diameter. The appearance on a computed tomography (CT) scan, with and without enhancement by contrast, is shown in Figure 1. There is a small nodule, approximately 1.5 cm in diameter, that appears to be located on the surface of the liver and shows striking enhancement during the arterial phase of the CT (Figure 1, right). Serum levels of alpha-fetoprotein and des-g-carboxy prothrombin (PIVKA-II) were within the reference range. Other investigations were performed but there was no evidence of additional intrahepatic or extrahepatic metastases. The tumor was presumed to be a local recurrence at the site of the hepatic incision or perhaps a solitary peritoneal metastasis. At laparotomy, there were extensive adhesions between the liver and the diaphragm and the tumor was resected en bloc with parts of both the diaphragm and liver. Macroscopically, the tumor occupied the intraphrenic space but not the subphrenic space (Figure 2). Histologically, there was a moderately-differentiated hepatocellular carcinoma that was covered in striated muscle (Figure 2, arrows). The appearance of the neoplasm was similar to that of the initial operative specimen. The diagnosis was that of a diaphragmatic metastasis from hepatocellular carcinoma. He remains in good health, 12 months after the second operation. The frequency of extrahepatic metastases in patients with hepatocellular carcinoma ranges from 13% to 37%. The most common sites for metastases are the lungs, lymph nodes, bones, adrenal glands and spleen. Metastases within the diaphragm appear to be extremely rare although there is one case report of ectopic hepatocellular carcinoma of the diaphragm. One possible mode of spread to the diaphragm is via the systemic circulation although it is difficult to believe that such a metastasis would be located close to the operative incision. Other possibilities include direct spread at the time of surgery or spread to the diaphragm through lymph channels that drain foreign material, pathogens and toxins from the peritoneal cavity. The latter route has been called the mesothelial stomata and appears to be the preferred mode of spread in this rare case.

Adenosquamous Carcinoma of the Pancreas

C 70-year-old man was admitted to the hospital because of general fatigue. His serum tumor marker levels for carboydrate antigen 19-9 was significantly elevated to 2975 U/mL the normal range is 38 U/mL). A computerized tomography can imaging of the abdomen showed a low density huge olid mass, approximately 10 cm in diameter in the tail of the ancreas (Figure A). Fluorodeoxyglucose positron emission toography (FDG-PET) showed a strong FDG uptake, with maxmum standardized uptake value (SUV) of 15.8 (Figure B). In a taging laparoscopy, we did not find any inoperable factors, such s peritoneal dissemination or liver deposits. Therefore, 7 days fter the staging laparoscopy, we performed an extended pancretectomy, which included resection of the spleen, the stomach, and he left kidney. The patient died 7 months after the operation ecause of liver metastasis. The histological diagnosis was adenoquamous carcinoma which had 2 components: a poorly differeniated adenocarcinoma with mucin production (Figure C) and quamous cell carcinoma with keratinization (Figure D). Adenosquamous carcinoma is a rare variant of ductal carcioma (1%– 4%).1 The prognosis is very poor, and the median urvival time is 6.8 months after surgery.1 Therefore, preopertive diagnosis is very important to predict a poor prognosis. ahemtullah et al2 reported that tumor cell necrosis was hisologically present in 86 percent of 14 patients. Our FDG-PET mage also shows central necrosis, a cold spot in the center of he tumor, but the surrounding area shows an extremely strong DG accumulation. Pancreatic cancer usually does not show a igh FDG uptake. In our institutes, the mean SUV level of esected ductal pancreatic cancer is 4.7 2.5 (n 21). Our atient’s SUV level was 3 times higher than that of other ancreatic cancer patients. FDG uptake reportedly predicts atient survival in many kinds of cancer. Our results may also eflect the aggressive behavior of the tumor. When FDG-PET hows a pancreatic cancer with a high uptake, we must consider hat the patient has an unusual type of pancreatic cancer.