Prospective validation of the CLIP score: a new prognostic system for patient with cirrhosis and hepatocellular carcinoma

Prognosis of patients with cirrhosis and hepatocellular carcinoma (HCC) depends on both residual liver function and tumor extension. The CLIP score includes Child-Pugh stage, tumor morphology and extension, serum alfa-fetoprotein (AFP) levels, and portal vein thrombosis. We externally validated the CLIP score and compared its discriminatory ability and predictive power with that of the Okuda staging system in 196 patients with cirrhosis and HCC prospectively enrolled in a randomized trial. No significant associations were found between the CLIP score and the age, sex, and pattern of viral infection. There was a strong correlation between the CLIP score and the Okuda stage, As of June 1999, 150 patients (76.5%) had died. Median survival time was 11 months, overall, and it was 36, 22, 9, 7, and 3 months for CLIP categories 0, 1, 2, 3, and 4 to 6, respectively. In multivariate analysis, the CLIP score had additional explanatory power above that of the Okuda stage. This was true for both patients treated with locoregional therapy or not. A quantitative estimation of 2-year survival predictive power showed that the CLIP score explained 37% of survival variability, compared with 21% explained by Okuda stage. In conclusion, the CLIP score, compared with the Okuda staging system, gives more accurate prognostic information, is statistically more efficient, and has a greater survival predictive power. It could be useful in treatment planning by improving baseline prognostic evaluation of patients with RCC, and could be used in prospective therapeutic trials as a stratification variable, reducing the variability of results owing to patient selection

Characterization of a fractured carbonate reservoir analogue in the southern Apennines (Italy)

In carbonate reservoirs characterized by low matrix porosity, fracture networks represent the main factor controlling fluid migration and consequentially, the reservoir quality. As fracture distribution in buried reservoirs is difficult to study in detail, outcropping analogues represent the most relevant source to predict the fracture network characteristics in three dimensions and to constrain their evolution through geological time. In this study, joints and veins have been analyzed at various scales in a carbonate succession cropping out in the southern Apennines. This succession is considered as a geological analogue of subsurface carbonate reservoirs hosting the Val D’Agri and Tempa Rossa oil fields in the Basilicata region. The studied succession, located at Mt. Chianello (Campania region), comprises a 1200 m thick sequence of Cretaceous shallow water carbonates characterized by an alternation of dolomitic and calcareous beds, with variable textures and crystal sizes, covered by silicoclastic deposits of Burdigalian age. The first phase of this work is focused on the structural analysis of this kilometre-sized outcrop of allochthonous carbonate units by means of the study of faults and fractures and their relationships with folds, as well as their crosscutting relationships. Structural and paleostress analyses allowed the writer to unravel a superposed deformation pattern within a general framework of convergent continental margin evolution, following the stages of Mesozoic extension. The reconstructed tectonic evolution involves: (i) early extensional faulting and fracturing associated with bending of the foreland lithosphere during forebulge and foredeep stages (including the development of both ‘tangential’ and ‘radial’ normal faults and tensile fractures; Early-Middle Miocene); (ii) large-scale thrusting and folding (Late Miocene); (iii) transcurrent faulting (including two distinct sub-stages characterized by different remote stress fields; Pliocene-Early Pleistocene), and (iv) extensional faulting (late Quaternary). Stage (i) normal faults – generally occurring as conjugate sets – and related fractures and veins are variably deformed and overprinted by later horizontal shortening. Despite having experienced such a long and complex structural history, the studied carbonates are characterized by a ‘background’ fracture network – including two joint/vein sets orthogonal to each other and to bedding – that appears to be associated with the early fault sets that formed during the first (foredeep/forebulge-related) deformation stage. Therefore, away from younger (Late Miocene to Quaternary) fault zones, the permeability structure of the studied carbonates appears to be essentially controlled by the early, inherited fracture network. As a similar fracture network is likely to characterize also the buried Apulian Platform carbonates, representing the reservoir units for major oil fields in southern Italy, the results also bear possible implications for a better understanding of fluid flow in the subsurface and related hydrocarbon production. The next part of this work is mainly aimed at analyzing the dependence of different geological parameters such as lithology, bed thickness, crystal size and matrix porosity controlling the spatial and statistical distribution of stratabound and non-stratabound fracture systems (sensu Odling et al., 1999), away from major fault damage zones. Stratabound fractures form, together with bedding-parallel joints bounding mechanical layers, a permeable network at the meter scale, transporting the fluids toward the main fault damage zones. The stratabound fracture systems exhibit a regular spacing and aperture values of the order of the tenths of millimetres. The analysis of fractures from single-bed scan lines provides confirms the well-known notion that bed thickness is the dominant parameter controlling stratabound fracture distribution, whereas lithology and textures do not play a major role. Furthermore, mechanical bed thickness appears to control also the stratabound fracture-related porosity. The higher values were reached in thinner beds (i.e. 0.8%), which are characterized by a densely spaced distribution of fractures. At a smaller scale, down to the crystal size, non-stratabound fractures form a capillary network conveying fluids within the rock mass. The examined fracture system exhibit a random spatial distribution along a single mechanical unit, whereas the fracture aperture values are roughly regulated by the corresponding lengths. Geological parameters like texture and lithology do not seem to control the fracture intensity at outcrop scale. However the multi-scale fracture analysis carried out on Aptian-Albian limestone and dolomite adjacent mechanical layers points out that, although the studied carbonates have been subjected to a uniform regional stress field, the fracture deformation style may vary from one mechanical unit to the next. In particular, micro-scale studies performed on thin sections and acetate peels, showed that the longitudinal strain in carbonate rocks is accommodated by fractures (joints and veins), mechanical twins affecting the calcite crystals within the veins, and micro-cracks in dolomite crystals. The results of the statistical analysis of non-stratabound microfracture density indicate that the role of crystal size largely overcomes that of lithology in controlling micro-scale rock strain, as fine-grained dolomites behave similarly to limestones with a comparable particle size. In particular, dolomites exhibit an inverse relationship between crystal size and the maximum fracture density (MFD; excluding micro-cracks), well described by a power law. This dependency for dolomites seems to be valid also in the buried reservoir, as proved by combining micro-fracture data of surface analogue with those collected on acetate peels representing the drilling cores(i.e. core 3, depth 5071-5077 m and core 4, depth 5276-5280 m) of Gorgolione 1 well (Tempa Rossa oil field). Moreover, the crystal size represents the main factor controlling the amount of finite strain related to the ratio between micro-cracks and micro-fractures in dolomites. Generally this ratio tends to increase with the increasing crystal size. Although the micro-cracks are ubiquitous in coarse dolomites, their role in the fluid circulation within the rock mass is negligible, being non-connected and sealed by mineralization. For all these reasons, the crystal size can be considered the main parameter controlling the fracture distribution at micro-scale and therefore, it influences significantly the hydraulic behavior of non-stratabound fracture systems. The third and final section of this thesis includes a structural and diagenetic investigation performed on microstructures (veins and stylolites) hosted in the Aptian- Albian part of the analyzed succession. The interactions among petrographic and microtectonic analysis, kinematic evolution of the Mt. Chianello ridge and inferred paleostress conditions, are described in details. This study documents different episodes of vein (fracture) formation, detected by matching the macro- and micro-scale observations with cathodoluminescence analysis (CL). The isotopic composition of cements filling the different fracture sets revealed a limited interaction with the host rock. The densely spaced early veins, forming together with two tensile joint sets the planar structure network affecting the whole succession, record the effects of multiple fracturing events. Early fractures (joints and veins) and normal faults formed as a consequence of the extension related to foreland bending, in the Early-Middle Miocene time. Subsequently during the incorporation of the Mt. Chianello carbonates in the Apennine accretionary wedge, the progressive layer parallel shortening (LPS) caused the formation of bedding-parallel veins and development of vertical stylolitic planes. Finally, during the following uplift and final emersion stages (post-LPS veins), the latest calcite cement generations were precipitated from meteoric fluids circulating along fractures associated with strike-slip fault systems and late extensional faults. Despite the numerous episodes of cementation, obliterating most of the small fractures, a considerable number of larger fractures (joints) showing on average aperture higher than 0.5 mm are still open and appear to control fluid flow in the surface analogue. The fracture analysis carried out on the Mt. Chianello carbonates represents an integrated approach that can be applied to fractured layered carbonate analogues. The results of different parts of this thesis can provide useful parameters for the characterization, modelling and simulation of carbonate reservoirs in general, and of reservoirs for the hydrocarbons of the Basilicata region, specifically

Serum immunoreactive pancreatic lipase and cationic trypsinogen for the assessment of exocrine pancreatic function in older patients with cystic fibrosis

Indirect and qualitative tests of pancreatic function are commonly used to screen patients with cystic fibrosis for pancreatic insufficiency. In an attempt to develop a more quantitative assessment, we compared the usefulness of measuring serum pancreatic lipase using a newly developed enzyme-linked immunosorbent immunoassay with that of cationic trypsinogen using a radioimmunoassay in the assessment of exocrine pancreatic function in patients with cystic fibrosis. Previously, we have shown neither lipase nor trypsinogen to be of use in assessing pancreatic function prior to 5 years of age because the majority of patients with cystic fibrosis in early infancy have elevated serum levels regardless of pancreatic function. Therefore, we studied 77 patients with cystic fibrosis older than 5 years of age, 41 with steatorrhea and 36 without steatorrhea. In addition, 28 of 77 patients consented to undergo a quantitative pancreatic stimulation test. There was a significant difference between the steatorrheic and nonsteatorrheic patients with the steatorrheic group having lower lipase and trypsinogen values than the nonsteatorrheic group (P < .001). Sensitivities and specificities in detecting steatorrhea were 95% and 86%, respectively, for lipase and 93% and 92%, respectively, for trypsinogen. No correlations were found between the serum levels of lipase and trypsinogen and their respective duodenal concentrations because of abnormally high serum levels of both enzymes found in some nonsteatorrheic patients. We conclude from this study that both serum lipase and trypsinogen levels accurately detect steatorrhea in patients with cystic fibrosis who are older than 5 years but are imprecise indicators of specific pancreatic exocrine function above the level needed for normal fat absorption

The role of stratabound fractures for fluid migration pathways and storage in well-bedded carbonates

Fracture analysis, carried out on two reservoir analogues cropping out at Faito and Chianello Mts. (southern Italy) allowed us to unravel the role of stratabound joint networks for oil migration and storage within well-bedded carbonate successions. The fracture regression analysis pointed out that stratabound fracture aperture increases as a function of bed thickness according to a linear law, independently by the lithological characteristics of the analyzed rock. Furthermore, statistical results suggest that fracture aperture and spacing exhibit, for each bed thickness value, a lognormal probability distribution. The estimation of the stratabound fracture porosity allowed us to identify, in well-bedded sedimentary successions, three classes of multilayer packages: (i) thin beds, characte - rized by a dual role of permeable pathways and oil storage systems; (ii) medium sized beds, showing limited permeability and porosity values and (iii) thick beds, acting as highly permeable pathways and showing a negligible storage capacity. Our results permit a full characterization and modeling of stratabound fracture networks. In particular, they provide a powerful tool for predicting preferential fluid pathways and major oil storage systems based on bed thickness data, within the framework of an analysis that may be further enhanced by the integration of petrophysics data