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.

Usefulness of EUS combined with contrast-enhancement in the differential diagnosis of malignant versus benign and preoperative localization of pancreatic endocrine tumors.

BACKGROUND: Pancreatic endocrine tumors (PETs) develop in relatively few patients, but they are often difficult to diagnose because of their small size and various clinical symptoms. OBJECTIVE: The aim of this study was to investigate the usefulness of EUS combined with contrast enhancement (CE-EUS) in the preoperative localization of PETs and the differentiation between malignant and benign PETs. DESIGN AND SETTING: Single-center retrospective study. PATIENTS: Sixty-two pathologically certified PETs of 41 patients who underwent EUS, multiphasic multidetector computed tomography (MDCT), and transabdominal US at our institute since 2001. INTERVENTIONS: Intravenous injection of US contrast media. MAIN OUTCOME MEASUREMENTS: Comparison of EUS, MDCT, and US in the preoperative identification of PETs, and the characteristic findings of EUS with malignancy. RESULTS: EUS showed high sensitivity (95.1%) in identifying PETs compared with MDCT (80.6%) and US (45.2%). Multivariable logistic regression analysis showed that heterogeneous ultrasonographic texture was the most significant factor for malignancy (OR = 53.33; 95% CI, 10.79-263.58). Most heterogeneous hypoechoic areas and anechoic areas corresponded to hemorrhage or necrosis on pathologic examination. They were identified as filling defects in CE-EUS and were more clearly recognized than in conventional EUS. LIMITATIONS: Retrospective study. CONCLUSION: EUS has higher sensitivity in preoperative localization of PETs compared with MDCT and US. The characteristics of EUS and CE-EUS findings in malignant PETs were clarified, and they will improve the diagnostic accuracy of PETs.

EUS-FNA predicts 5-year survival in pancreatic endocrine tumors.

BACKGROUND: Pancreatic endocrine tumors (PETs) differ in clinical behavior and prognosis. Determination of malignant potential through specimens obtained by EUS-FNA can help in the management of these patients. OBJECTIVE: To determine the value of EUS-FNA for diagnosing PETs and for classifying their underlying malignant potential based on the World Health Organization (WHO) classification. DESIGN: Single-center, retrospective, cohort study. SETTING: Tertiary referral hospital. PATIENTS: This study involved 86 consecutive patients (44 men, mean age 58 +/- 14 years) who had been diagnosed with PETs and submitted to EUS-FNA from January 1999 to August 2008. INTERVENTION: EUS-FNA of a pancreatic mass and/or a metastasis site. Immunohistochemistry on microbiopsies or on monolayer cytology was routinely used. The lesions were classified as recommended by the WHO. MAIN OUTCOME MEASUREMENTS: EUS-FNA sensitivity and 5-year survival rate. RESULTS: Overall, in 90% (77 of 86) of patients in this study, PET was diagnosed with EUS-FNA. The sensitivity did not vary with tumor size, type, location, or the presence of hormonal secretion. Of 86 patients, 30 (35%) were submitted to surgical resection. The kappa correlation index between the WHO classification obtained by EUS-FNA and by surgery was 0.38 (P = .003). Major discrepancies were found in the group of patients diagnosed with endocrine tumor of uncertain behavior by EUS-FNA, because 72% turned out to have well-differentiated endocrine carcinoma. Sixteen patients (27%) died during a mean follow-up period of 34 +/- 27 months. The 5-year survival rates were 100% for endocrine tumors, 68% for well-differentiated endocrine carcinomas, and 30% for poorly differentiated endocrine carcinomas (P = .008, log-rank test). LIMITATIONS: Retrospective design, selection bias, and small sample size. CONCLUSIONS: This largest single-center experience to date demonstrated the accuracy of EUS-FNA in diagnosing and determining the malignant behavior of PETs. EUS-FNA findings predict 5-year survival in patients with PETs.

Pancreatic endocrine tumor EUS-guided FNA DNA microsatellite loss and mortality.

BACKGROUND: The clinical course of pancreatic endocrine tumors (PET) depends on tumor size, the presence of invasion or metastasis, the Ki-67 index, mitoses per high power field, and mutational damage. Most of this information is not available before surgery for clinical decision making or prognostication. OBJECTIVE: To evaluate PET EUS-guided FNA (EUS-FNA) microsatellite loss analysis in the context of PET-related mortality. DESIGN: A single institution retrospective cohort. PATIENTS: Patients with PET diagnosed by EUS-FNA who underwent DNA microsatellite loss analysis and at least 1 year of follow-up or subsequent death. INTERVENTION: PET microsatellite loss analysis results and current clinical status were compared. RESULTS: Twenty-nine patients were included in the final analysis; the mean age of the patients was 57 years, and 10 were women (35%). The mean follow-up was 33.7 months (median 30 months, range 2-66 months). Twelve patients had disease progression, and 8 died, all from disease-specific causes. Malignant PET contained multiple microsatellite losses, with a median fractional allelic loss (FAL) of 0.37 (range 0.12-0.69, interquartile range [IQR] 0.23-0.42), significantly different from benign PET, median FAL 0 (range 0-0.18, IQR 0-0.08, P < .0001). Survival analysis revealed a significant difference in disease recurrence or progression at 2 years (P < .0001) and in the 5-year survival between patients with FAL 0.2 (P < .0001). Logistic regression could not be performed because of the perfect association between an FAL >0.2 and disease status or mortality. LIMITATIONS: Retrospective design, referral bias, and DNA analysis availability. CONCLUSIONS: PET EUS-FNA microsatellite loss analysis provides preoperative prognostic information. An FAL >0.2 is not only associated with disease progression but also with mortality.

[A long-term survival case of unresectable malignant pancreatic endocrine tumor successfully treated with systemic chemotherapy].

A 55-year-old man was admitted to our hospital because of high grade fever in October 1999. Computed tomography showed a solid tumor in the tail of the pancreas with multiple liver tumors. We diagnosed him as unresectable pancreatic tail cancer with multiple liver metastases at first, so systemic chemotherapy using UFT was performed. Gradually, liver metastases were slightly reduced, and tumor markers (CEA, CA19-9) decreased to the normal range. In April 2001, percutaneous transhepatic tumor biopsy was performed. Histopathological examination revealed a malignant pancreatic endocrine tumor. Long NC had continued by using the UFT regimen. But because tumors had gradually grown since October 2003, the chemotherapy with S-1 was followed by gemcitabine (GEM). The patient has now survived for 7.5 years while receiving the combined chemotherapy of S-1/GEM.

Successful pancreatectomy with en-bloc resection of the celiac artery and portal vein for pancreatic endocrine carcinoma.

Invasion to the celiac axis and portal vein is one reason for the unresectability of pancreatic carcinoma of the body and tail. Some authors advocate a radical distal pancreatectomy with en-bloc resection of the celiac artery and portal vein. However, long-term survival is still rare. We report here on a very rare, long-term survivor of a locally-advanced endocrine carcinoma of the body of the pancreas that was treated by distal pancreatectomy with en-bloc resection of the celiac artery and portal vein. The patient recovered well postoperatively, and has survived for 55 months without evidence of recurrence. The experience gained in the present case suggests that radical pancreatectomy with en-bloc resection of the celiac artery and portal vein is a potential approach that might increase tumor resectability and improve the prognosis of patients with locally-advanced endocrine carcinomas of the pancreas.

Gallium-67/gallium-68-[DFO]-octreotide--a potential radiopharmaceutical for PET imaging of somatostatin receptor-positive tumors: synthesis and radiolabeling in vitro and preliminary in vivo studies.

UNLABELLED: When labeled with gamma-emitting radionuclides, somatostatin analogs have the potential to localize somatostatin receptor-positive tumors using gamma camera scintigraphy. We present a somatostatin analog, [DFO]-octreotide (SDZ 216-927), that comprises desferrioxamine B coupled to octreotide via a succinyl linker. This conjugate can be labeled with either 67Ga for gamma scintigraphy or 68Ga for PET imaging. The 67Ga-labeled conjugate is stable in vitro to autoradiolysis over a 24-hr period. METHODS: Rats bearing a somatostatin receptor-positive pancreatic islet cell tumor were injected with 20 MBq of 67Ga[DFO]-octreotide (33 GBq 67Ga/mumole). RESULTS: After 1 hr, the accumulation of 67Ga[DFO]-octreotide was 0.38 +/- 0.08 %ID/g and the tumor-to-nontumor ratios for blood, muscle, liver and intestine were 2.5, 7.4, 1.9 and 1.6, respectively. PET studies with 68Ga[DFO]-octreotide recorded a very rapid accumulation at the tumor and a subsequent residence half-life of about 6 hr. CONCLUSION: Gallium-68-[DFO]-octreotide can be used in PET studies to diagnose receptor-positive tumors such as gastroenteropancreatic, small-cell lung and breast tumors.

Intraductal growth of a nonfunctioning endocrine tumor of the pancreas.

Intraductal growth of nonfunctioning endocrine tumors of the pancreas may be very rare, and our survey of literature shows only two cases have been described. We report a case of a 43-year-old man with a nonfunctioning endocrine tumor of the pancreas that uniquely grew within the lumen of the main pancreatic duct (MPD) without ductal involvement and completely obstructed the MPD. Endoscopic ultrasonography (EUS) and endoscopic retrograde cholangiopancreatography (ERCP) were very helpful to delineate the intraductal growth of the tumor and to determine the resection line of the pancreas. A nonfunctioning pancreatic endocrine tumor is important to consider on differential diagnoses when complete obstruction of the MPD is demonstrated on ERCP. It is speculated that the tumor originated from precursor cells of the pancreatic duct or islet cells adjacent to the MPD and slowly proliferated within the lumen of the MPD.

Thin-section contrast-enhanced computed tomography accurately predicts the resectability of malignant pancreatic neoplasms.

A prospective diagnostic study was designed to determine the ability of thin-section contrast-enhanced computed tomography (CT) to predict the resectability of malignant neoplasms of the pancreatic head. Patients with a presumed resectable pancreatic neoplasm referred during a 21-month period were studied with abdominal CT performed at 1.5-mm section thickness and 5-mm slice interval during the bolus phase of intravenous contrast enhancement. CT criteria for resectability included the absence of extrapancreatic disease, no evidence of arterial encasement, and a patent superior mesenteric-portal venous confluence. Of 145 patients evaluated, 42 were considered to have resectable tumors by CT criteria, and 37 (88%) underwent potentially curative pancreaticoduodenectomy. Six patients were found to have a microscopically positive retroperitoneal resection margin; no patient had a grossly positive resection margin. Five (12%) of 42 patients were found at laparotomy to have unresectable, locally advanced or metastatic tumors. Thin-section contrast-enhanced CT is an essential component of the preoperative evaluation for pancreaticoduodenectomy and can prevent needles laparotomy in most patients with locally advanced or metastatic disease.

Endoscopic ultrasonography of nonfunctioning pancreatic islet cell tumors with histologic correlation.

BACKGROUND/AIMS: Preoperative differentiation of benign and malignant pancreatic nonfunctioning islet cell tumors remains problematic. The present study aimed to evaluate endoscopic ultrasonography (EUS) features of benign and malignant tumors with histologic correlation. METHODOLOGY: Ten patients with surgically resected nonfunctioning pancreatic islet cell tumors were retrospectively reviewed. RESULTS: EUS demonstrated a homogenous hypoechoic (n=2) or hyperechoic (n=1) mass in the 3 benign tumors. EUS showed a hypoechoic mass with an irregular central hyperechoic portion (n=4), a hyperechoic mass with an irregular central hypoechoic portion (n=1), a cystic mass with a large irregular internal hypoechoic portion (n=1), or a hypoechoic mass within the entire lumen of the main pancreatic duct (MPD) (n=1) in the 7 malignant tumors. Histologically, the irregular central portions of the malignant tumors corresponded to necrosis, hemorrhage, fibrosis with hyalinosis, cystic degeneration, and/or calcification. Complete obstruction of the main pancreatic duct on EUS was observed in the 2 malignant tumors. The echogenicity of the tumors was closely associated with arrangement of tumor cells and quantity of fibrous stroma. CONCLUSIONS: Heterogeneous internal structures and complete obstruction of the main pancreatic duct are considered as important EUS features that are suggestive of malignancy in nonfunctioning pancreatic islet cell tumors.

Early massive accumulation of In-111 pentetreotide in a metastatic liver tumor of islet cell carcinoma.

A 62-year-old woman was examined with In-111 pentetreotide and Ga-67 citrate. She had undergone an operation to resect a neuroendocrine tumor of the pancreas and still had masses in the liver. One of her hepatic lesions had been biopsied and acinar cell carcinoma was suspected. Fluid in the cyst of the tumor, however, contained a high concentration of gastrin and the tumor was strongly suspected of being a metastasis from the neuroendocrine tumor of the pancreas. The hepatic tumors quickly accumulated In-111 pentetreotide immediately after the injection, but there was no Ga-67 citrate uptake in the tumor. Five months after pentetreotide scintigraphy, her hepatic tumors were resected and histologically proven to be metastasis of islet cell carcinoma. In-111 pentetreotide provides information of the somatostatin-receptor status on the tumor and supports the diagnosis made by hormonal survey.

[Small nodular lesions of the pancreas: differential diagnosis with ultrasound angiography].

Ultrasound angiography (USAG), sonographic imaging of the blood flow in an organ or tissue obtained by carbon dioxide infusion into the supplying artery, was performed on 28 pancreatic nodular lesions less than 3 cm in diameter. The hemodynamics of tumors observed with USAG were divided into three groups: hypovascular, isovascular, and hypervascular, compared with the adjacent pancreatic tissue. Most of hypovascular nodules were duct cell carcinoma (sensitivity 94.1%, specificity 90.4%), while isovascular lesion was the characteristic of inflammatory masses (sensitivity 100%, specificity 95.8%). Hypervascular cases included all of the mucin producing tumors and islet cell tumors but only one case of duct cell carcinoma. So you can almost exclude duct cell carcinoma as an diagnosis in vascular rich tumors (negative predictive value 83.6%). These results were compared with those on conventional x-ray angiograms and incremental CT scans. Ultrasound angiography enabled us to detect more slight differences of tumor vascularity than the other modalities. Thus we conclude that USAG can be a useful diagnostic aid in small mass lesions of the pancreas.

First-line chemotherapy with capecitabine and temozolomide in patients with metastatic pancreatic endocrine carcinomas.

BACKGROUND: Temozolomide is an active agent in metastatic pancreatic endocrine carcinomas. In vitro data indicate that the combination of capecitabine and temozolomide is synergistic for induction of apoptosis in neuroendocrine tumor cell lines. The authors retrospectively evaluated the efficacy of capecitabine and temozolomide in 30 patients with metastatic pancreatic endocrine carcinomas to assess response rate, progression free survival (PFS), and overall survival (OS). METHODS: Patients with metastatic, well, or moderately differentiated pancreatic endocrine carcinomas who had not received prior systemic chemotherapy were treated with capecitabine (750 mg/m² twice daily, days 1-14) and temozolomide (200 mg/m² once daily, days 10-14) every 28 days. RESULTS: Among 30 patients treated, 21 (70%) patients achieved an objective radiographic response. Median progression-free survival was 18 months. The rate of survival at two years was 92%. Only 4 patients (12%) experienced grade 3 or 4 adverse events. CONCLUSIONS: The combination of capecitabine and temozolomide is associated with an exceptionally high and durable response rate in metastatic endocrine carcinomas of the pancreas. Clinical endpoints, including response rate, survival, and toxicity, are superior to those observed with streptozocin-based regimens.

Multidetector computed tomography and neuroendocrine pancreaticoduodenal tumors.

PURPOSE: To investigate the accuracy of dedicated pancreatic multidetector computed tomography (MDCT) in the diagnosis of neuroendocrine pancreaticoduodenal tumors (NPTs). MATERIAL AND METHODS: MDCT and other imaging studies in patients with suspected NPTs were identified. Thirty dedicated MDCT studies were done in 23 patients. Fourteen patients (16 operations) subsequently had surgery. Imaging reports were reviewed and findings compared with surgical findings and findings in other imaging studies. RESULTS: Patients with surgery: 19 NPTs (16 extrapancreatic gastrinomas and 3 pancreatic NPTs) were identified at surgery. MDCT identified 16 and somatostatin receptor scintigraphy (SRS) 11 out of 19 tumors. Endoscopic ultrasound detected 11 out of 14 NPTs. Patients without surgery: In 4 out of 9 patients, no NPTs were identified at MDCT. CONCLUSION: Dedicated MDCT of the pancreas can identify many NPTs, including small duodenal and periduodenal tumors, and the detection rate is better than reported in the older literature on CT.

Differential diagnosis of benign versus malignant nonfunctioning islet cell tumors of the pancreas: the roles of EUS and ERCP.

BACKGROUND: Differentiation between benign and malignant nonfunctioning islet cell tumors of the pancreas before surgery is often difficult. The roles of EUS and ERCP were evaluated in the differential diagnosis of these tumors. METHODS: Seven patients with histologically confirmed nonfunctioning islet cell tumors (4 benign, 3 malignant) underwent EUS and ERCP. OBSERVATIONS: EUS demonstrated a homogeneous hypoechoic mass or a hypoechoic mass with a regular central echogenic area in the 4 cases of benign tumor, and a hypoechoic mass with an irregular central echogenic area in all 3 cases of malignant tumor. The irregular central echogenic area corresponded to severe hemorrhage, necrosis, or fibrosis with hyalinosis (hyaline degeneration) on pathologic examination. ERCP demonstrated displacement or complete obstruction (because of ductal invasion) of the main pancreatic duct in 2 patients with malignant tumors and no abnormalities in the other 5 cases. CONCLUSIONS: In patients with nonfunctioning islet cell tumors, a hypoechoic mass with an irregular central echogenic area on EUS or complete obstruction of the main pancreatic duct on ERCP suggests malignancy.