Xenon-inhalation computed tomography for noninvasive quantitative measurement of tissue blood flow in pancreatic tumor.

BACKGROUND AND AIMS: The purpose of this prospective study was to demonstrate the ability to measure pancreatic tumor tissue blood flow (TBF) with a noninvasive method using xenon inhalation computed tomography (xenon-CT) and to correlate TBF with histological features, particularly microvascular density (MVD). METHODS: TBFs of pancreatic tumors in 14 consecutive patients were measured by means of xenon-CT at diagnosis and following therapy. Serial abdominal CT scans were obtained before and after inhalation of nonradioactive xenon gas. TBF was calculated using the Fick principle. Furthermore, intratumoral microvessels were stained with anti-CD34 monoclonal antibodies before being quantified by light microscopy (×200). We evaluated MVD based on CD34 expression and correlated it with TBF. RESULTS: The quantitative TBF of pancreatic tumors measured by xenon CT ranged from 22.3 to 111.4 ml/min/100 g (mean ± SD, 59.6 ± 43.9 ml/min/100 g). High correlation (r = 0.885, P < 0.001) was observed between TBF and intratumoral MVD. CONCLUSION: Xenon-CT is feasible in patients with pancreatic tumors and is able to accurately estimate MVD noninvasively.

Fast cancer uptake of 99mTc-labelled bombesin (99mTc BN1).

In human blood, breakdown of gastrin-releasing peptide and other bombesin-related peptides occurs in less than 15 min. This quick enzymatic cleavage might impair the diagnostic use of labelled bombesin (BN). 99mTc-labelled bombesin (99mTc BN1) was injected intravenously and dynamic uptake data were acquired for diagnosing 26 cancers of different origin: 15 breast, 3 prostate, 5 colo-rectal, 1 pancreas, 2 small cell lung cancers and 1 gastrinoma. Background subtracted tumour uptake data were plotted against time and fitted with known mathematical functions. Twenty-three out of 26 cancers showed rapid increase of radioactivity followed by a radioactivity plateau, with some oscillations around the average plateau value. The time to 80% of max activity (T80) was the reference parameter to measure and to compare the uptake speeds. The slowest T80 was 7 min in one T1b breast cancer, gastrinoma reached T80 in 5 min and node-positive prostate cancers in 2 min. N+ breast cancers showed T80 at 3.62 +/- 0.75 min, N- breast cancers at 5.5 +/- 0.88 min (p < 0.02). When all the tumours were considered, N+ tumours showed T80 at 2.68 +/- 1.03 min and N- cancers at 5.5 +/- 0.82 min. In all the cancer types, the uptake of 99mTc BN was faster than 10 min. This result shows the ability of 99mTc BN to image tumours. The faster uptake by N+ versus N- cancers probably depends on the higher blood flow in N+ cancers.

Pancreatic endocrine tumors with major vascular abutment, involvement, or encasement and indication for resection.

BACKGROUND: Surgery for pancreatic endocrine tumors (PETs) with blood vessel involvement is controversial. HYPOTHESIS: Resection of PETs with major blood vessel involvement can be beneficial. DESIGN: The combined databases of the National Institutes of Health and Stanford University hospitals were queried. MAIN OUTCOME MEASURES: Operation, pathologic condition, complications, and disease-free and overall survival. RESULTS: Of 273 patients with PETs, 46 (17%) had preoperative computed tomography evidence of major vascular involvement. The mean size for the primary PET was 5.0 cm. The involved major vessel was as follows: portal vein (n = 20), superior mesenteric vein or superior mesenteric artery (n = 16), inferior vena cava (n = 4), splenic vein (n = 4), and heart (n = 2). Forty-two of 46 patients had a PET removed: 12 (27%) primary only, 30 (68%) with lymph nodes, and 18 (41%) with liver metastases. PETs were removed by either enucleation (n = 7) or resection (n = 35). Resections included distal or subtotal pancreatectomy in 23, Whipple in 10, and total in 2. Eighteen patients had concomitant liver resection: 10 wedge resection and 8 anatomic resections. Nine patients had vascular reconstruction: each had reconstruction of the superior mesenteric vein and portal vein, and 1 had concomitant reconstruction of the superior mesenteric artery. There were no deaths, but 12 patients had complications. Eighteen patients (41%) were immediately disease free, and 5 recurred with follow-up, leaving 13 (30%) disease-free long term. The 10-year overall survival was 60%. Functional tumors were associated with a better overall survival (P < .001), and liver metastases decreased overall survival (P < .001). CONCLUSION: These findings suggest that surgical resection of PETs with vascular abutment/invasion and nodal or distant metastases is indicated.

Cellular proliferative fraction measured with topoisomerase IIalpha predicts malignancy in endocrine pancreatic tumors.

CONTEXT: Endocrine pancreatic tumors (EPTs) are rare lesions with varying biological behavior. Establishing malignancy is a challenge for clinicians and pathologists. OBJECTIVE: To establish the role of proliferative, apoptotic, angiogenic, and hormonal markers as predictors of malignancy in EPTs. DESIGN: Paraffin-embedded EPT samples were studied for prognostic markers. PATIENTS: Twenty-one consecutive patients with a diagnosis of EPT. MAIN OUTCOME MEASURES: The proliferative fraction (topoisomerase IIalpha), microvascular density (CD34), vascular endothelial growth factor expression, and estrogen receptor-beta (ERbeta) expression were studied by immunohistochemistry on all EPTs. Apoptosis was also assessed with terminal deoxynucleotidyl transferase nick-end labeling. RESULTS: We identified 13 benign and 8 malignant tumors. Topoisomerase IIalpha was significantly increased in malignant tumors (P =.001), while there were no differences in apoptosis, microvascular density, or vascular endothelial growth factor expression in association with malignancy. No correlation could be identified between microvascular density and vascular endothelial growth factor expression, and ERbeta was not detected. A receiver operating characteristic curve for topoisomerase IIalpha disclosed that above a labeling index of 13, the test had 88% sensitivity and 100% specificity for predicting malignancy. CONCLUSION: Cellular proliferation measured with topoisomerase IIalpha is a simple prognostic marker for malignancy in EPTs, unlike apoptosis, angiogenesis, or the presence of ERbeta, which were not associated with malignant behavior. These findings designate a defined field for future research on endocrine pancreatic carcinogenesis and a possible target for chemotherapeutic agents.

Effect of somatostatin analogue (octreotide) on blood flow to endocrine tumors metastatic to the liver: angiographic evaluation.

The effect of an octapeptide analogue of somatostatin, octreotide, on tumor blood flow was evaluated with angiography in eight patients with hepatic endocrine tumors; one patient had primary intrahepatic gastrinoma, two patients had hepatic metastases from gastrinomas, two patients had VIPomas (vasoactive intestinal polypeptide-secreting tumor), and three patients had carcinoid tumors. Octreotide caused a marked decrease in tumor blood flow in two patients with gastrinomas and two with VIPomas. One patient could not be evaluated due to the lack of a tumor blush on a control angiogram. In patients with carcinoid tumors, octreotide caused a slight reduction in blood flow through the tumors in two patients, while there was no change in one patient. Octreotide markedly decreased gastrin and gastric acid secretion in two of three patients with gastrinomas, lowered VIP and stopped the diarrhea in patients with VIPomas, and controlled symptoms in two of three patients with carcinoid tumors. The vasoactive effect of octreotide on hepatic endocrine tumors may be a direct action on tumor blood supply or secondary to inhibition of the endocrine tumor cell secretion and consequent decreased blood flow.