Endocrine Pancreatic Tumours and Helical CT: Contrast Enhancement Is Correlated with Microvascular Density, Histoprognostic Factors and Survival

Rodallec, M.; Vilgrain, Valérie; Couvelard, Anne; Rufat, Pierre; O’Toole, Dermot; Barrau, Vincent; Sauvanet, Alain; Ruszniewski, Philippe; Menu, Y.

doi:10.1159/000090026

Cited by 131 publications

(75 citation statements)

References 26 publications

(30 reference statements)

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“…4,18 Interestingly, it is correlated with contrast enhancement on CT scan which offers the possibility to assess endocrine tumor aggressiveness at the time of diagnosis. 27 Our study shows a moderate intraclass correlation coefficient of 0.48 inside single metastasis, demonstrating that there is a substantial variability in the microvascular density of endocrine metastases when it is evaluated on small, 1 mm diameter areas. This is in accordance with the fact that the values of microvascular density vary greatly according to the area in most tumor types and the homogeneous range between the two limits of agreement.…”

Section: Discussionmentioning

confidence: 57%

“…32 Finally, we observed better agreements with the microvascular density as a qualitative data which probably reflects that using three groups (low, moderate or high counting) could help to separate highly from low vascularized tumors in good correlation with imaging contrast enhancement, prognosis and, hopefully, response to antiangiogenic treatments. 27 Endocrine tumors usually express somatostatin receptors, although the subtypes and number of somatostatin receptors expressed in a certain tumor is very variable. However, somatostatin receptor type 2 is the major somatostatin receptor subtype in pancreatic endocrine tumors.…”

Section: Discussionmentioning

confidence: 99%

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Heterogeneity of tumor prognostic markers: a reproducibility study applied to liver metastases of pancreatic endocrine tumors

et al. 2009

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Liver biopsy of metastatic pancreatic endocrine tumors allows confirmation of the diagnosis and assessment of prognosis. However, sampling variability is a potential limitation. Our aim was to use the tissue microarray technique to assess the heterogeneity of three prognostic markers, ie, MIB-1 proliferation index, microvascular density and somatostatin receptor type 2, inside single or between synchronous or metachronous liver metastases of pancreatic endocrine tumors. Tissue microarrays were constructed, which included core biopsies taken from surgically resected liver metastases in 29 patients. MIB-1, microvascular density and somatostatin receptor type 2 were evaluated after immunostaining. The heterogeneity was highlighted by the calculation of the reproducibility of the values of two cores randomly selected among all the cores studied. For quantitative variables, it was assessed by the intraclass correlation coefficient and by a Bland-Altman approach. For qualitative variables, observed agreement and weighted j were given. A total of 184 liver metastases were analyzed. For MIB-1, the intraclass correlation coefficients were 0.63, 0.69 and 0.67 and for microvascular density, the intraclass correlation coefficients were 0.48, 0.60 and 0.00, respectively, in single, synchronous and metachronous liver metastases. The variability increased for higher mean values of microvascular density. For somatostatin receptor type 2, the observed agreements were 91% (j ¼ 0.81), 69% (j ¼ 0.49) and 79% (j ¼ 0.68) in single, synchronous and metachronous liver metastases, respectively. In conclusion, tissue microarray analysis identifies heterogeneity of protein expression in pancreatic endocrine metastases, which depends on the marker tested. The reproducibility is better for MIB-1 and somatostatin receptor type 2 than for microvascular density. Sampling variability should be taken into consideration as a potential limitation to the assessment of prognostic and therapeutic markers in biopsy samples from metastatic pancreatic endocrine tumors.

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Section: Discussionmentioning

confidence: 57%

Section: Discussionmentioning

confidence: 99%

Heterogeneity of tumor prognostic markers: a reproducibility study applied to liver metastases of pancreatic endocrine tumors

et al. 2009

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“…However, these were also predictive of radiological response, suggesting that any effect on time-related end points would be at least partly related to a treatment effect. A recent study by our group showed that microvessel density in pancreatic endocrine tumours is correlated with the vascular pattern of the tumour on helical CT (Rodallec et al, 2005). Knowing this, it appears consistent that the more vascularised the tumour, the better it responds to TACE.…”

Section: Discussionmentioning

confidence: 52%

Arterial phase enhancement and body mass index are predictors of response to chemoembolisation for liver metastases of endocrine tumours

et al. 2006

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Transcatheter arterial chemoembolisation (TACE) has been reported to be an efficient treatment of liver metastases of endocrine tumours in short series of patients. However, several factors seem to affect its results. The aim of this work is to identify predictors of response to TACE for liver metastases of endocrine tumours. A total of 163 TACE procedures were performed in 67 patients between 1994 and 2004. Forty-four patients were treated with streptozotocin and 23 with doxorubicin. Primary tumour was located in the pancreas for 19 patients, and had been removed in 43. Thirty-eight tumours were functioning. Response rate was 37% (confidence interval [CI] 95%: 28 -49%). Median time to progression (TTP) was 14.5 months (CI 95%: 9 -41). In multivariate analysis (n ¼ 43), predictors of tumour response were body mass index (BMI) (odds ratio [OR]: 1.3; CI 95%: 1.04 -1.63; P ¼ 0.022), functioning type of tumour (OR: 7.31; CI 95%: 1.26 -42.5; P ¼ 0.027), arterial phase enhancement on abdominal computed tomography (CT) (OR: 8.11; CI 95%:1.06 -62; P ¼ 0.044) and use of streptozotocin for cytotoxic agent (OR: 21.3; CI 95%: 1.48 -306; P ¼ 0.025). Analysis of TTP predictors showed that BMI (hazard ratio [HR]: 0.85; CI 95%: 0.76 -0.86; P ¼ 0.01) and arterial phase enhancement (HR: 0.3; CI 95%: 0.12 -0.73; P ¼ 0.008) were associated with delayed progression. This large study confirms the previously reported results of TACE regarding its efficacy for the treatment of liver metastases of endocrine tumours. Arterial phase enhancement on abdominal CT and BMI are predictors of treatment's efficacy. Streptozotocin should be the preferred cytotoxic agent in order to save anthracycline for systemic chemotherapy.

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“…Experimental applications of pCT to PanNETs reported interesting results. Rodallec et al [69] and D'Assignies et al [70] reported that pCT features were correlated with MVD; moreover, BF values of benign PanNETs were higher than those of uncertain behavior tumors and carcinomas, and significant correlations were reported between BF, MTT and proliferation index, microscopic vascular neoplastic involvement and presence of nodal or liver metastases. Regarding staging, Ng et al [71] reported that BF and hepatic arterial fraction were significantly higher in liver metastases from PanNETs than in healthy liver, thus reflecting an increased arterial blood supply to metastatic lesions; opposite relationships were found for MTT and PS.…”

Section: Pancreatic Tumorsmentioning

confidence: 98%

Prognostication and response assessment in liver and pancreatic tumors: The new imaging

Robertis¹,

Martini²,

Demozzi³

et al. 2015

WJG

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Diffusion-weighted imaging (DWI), dynamic contrastenhanced magnetic resonance imaging (DCE-MRI) and perfusion computed tomography (CT) are technical improvements of morphologic imaging that can evaluate functional properties of hepato-bilio-pancreatic tumors during conventional MRI or CT examinations. Nevertheless, the term "functional imaging" is commonly used to describe molecular imaging techniques, as positron emission tomography (PET) CT/MRI, which still represent the most widely used methods for the evaluation of functional properties of solid neoplasms; unlike PET or single photon emission computed tomography, functional imaging techniques applied to conventional MRI/CT examinations do not require the administration of radiolabeled drugs or specific equipments. Moreover, DWI and DCE-MRI can be performed during the same session, thus providing a comprehensive "one-step" morphological and functional evaluation of hepato-bilio-pancreatic tumors. Literature data reveal that functional imaging techniques could be proposed for the evaluation of these tumors before treatment, given that they may improve staging and predict prognosis or clinical outcome. Microscopic changes within neoplastic tissues induced by treatments can be detected and quantified with functional imaging, therefore these techniques could be used also for posttreatment assessment, even at an early stage. or altered cellular membranes will present diffusion restriction, which is depicted as signal hyperintensity areas on high b-value DW images and hypointensity on the apparent diffusion coefficient (ADC) maps; ADC measurement can also quantify water molecules' diffusion. As dedifferentiation or therapies may induce microscopic changes in neoplastic tissues that could modify water molecules' diffusion, DWI can distinguish between different degrees of malignancy and can be also proposed for post-treatment monitoring. Moreover, DWI can be performed in a single session with DCE-MRI, thus providing a comprehensive "one-step" morphological and functional evaluation of hepatobilio-pancreatic tumors.Perfusion imaging techniques evaluate changes in signal intensity (DCE-MRI) or density (pCT) after contrast medium injection, being therefore able to assess microvascularization through the evaluation of the dynamics of contrast medium distribution from vessels to the neoplastic tissue. Perfusion parameters are therefore theoretically good candidates for the evaluation of microscopic vascular differences between lesions with different pathological grade and for the assessment of treatment response, especially after chemoembolization or during treatments with antiangiogenic drugs.This editorial analyzes up-to-date literature data regarding the application of functional imaging techniques, apart from molecular imaging, to hepatic and pancreatic tumors, with particular emphasis on correlations to pathological features, prognostic stratification and therapeutic response assessment. FUNCTIONAL IMAGING TECHNIQUES: TECHNICAL BASESIn 1965 Stejskal and Tanne...

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Endocrine Pancreatic Tumours and Helical CT: Contrast Enhancement Is Correlated with Microvascular Density, Histoprognostic Factors and Survival

Cited by 131 publications

References 26 publications

Heterogeneity of tumor prognostic markers: a reproducibility study applied to liver metastases of pancreatic endocrine tumors

Heterogeneity of tumor prognostic markers: a reproducibility study applied to liver metastases of pancreatic endocrine tumors

Arterial phase enhancement and body mass index are predictors of response to chemoembolisation for liver metastases of endocrine tumours

Prognostication and response assessment in liver and pancreatic tumors: The new imaging

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