Abstract Background The treatment of hepatic metastases from gastric cancer is controversial, due to biologic aggressiveness of the disease. Objective To survey the clinical approach to the subset of ...patients presenting with metachronous hepatic metastases as sole site of recurrence after curative resection of gastric cancer, focusing on the results achieved by different therapies and to investigate the prognostic factors of major clinical relevance. Methods Retrospective multi-center chart review evaluating 73 patients, previously submitted to D ≥ 2 gastrectomy for gastric cancer, who developed exclusive hepatic recurrence. Prognostic factors related to the patient, to the gastric malignancy and its treatment, and to the metastatic disease and its therapy were evaluated. Results Forty-five patients received supportive care, 17 were submitted to chemotherapy, and 11 to hepatic resection. Survival was independently influenced by the variables T ( p = 0.019), N ( p = 0.05) and G ( p = 0.018) of the gastric primary and by the therapeutic approach to the metastases ( p < 0.005). In particular, T4 gastric cancer, presence of lymph-node metastases and G3 tumor displayed a negative prognostic value. Therapeutic approach to the metastases was the principal prognostic variable: 1, 2, and 3 years survival rates were 22.2%, 4.4% and 2.2%, respectively, for patients without specific treatment; 44.9%, 12.8% and 6.4% after chemotherapy ( p = 0.08) and 80.8%, 30.3% and 20.2% after surgical resection ( p < 0.001). Conclusions Our data suggest some clinical criteria that may facilitate selection of therapy for patients with hepatic recurrence after primary gastric cancer resection. The best survival rates are associated with surgical treatment, which should be chosen whenever possible.
To evaluate the predictive factors, the therapy, and the prognosis of intrahepatic recurrence (IR) after surgery for hepatocellular carcinoma (HCC).
The predictive factors of IR are debated. To class ...the recurrence according to the modality of presentation may help to find a correlation and to select the right therapy for the recurrence.
A total of 213 patients were evaluated. Risk factors for recurrence were related to time (<2 years and >2 years) and type of presentation (marginal, nodular, and diffuse). Prognosis and therapy for the recurrence were studied in each group of patients.
IR was observed in 143 patients; 109 were early (group 1) and 34 late recurrences (group 2). Cirrhosis, chronic active hepatitis (CAH) and HCV positivity were independently related to the risk of recurrence with a cumulative effect (92.5% of recurrences in patients with 3 prognostic factors). For group 1, the neoplastic vascular infiltration together with cirrhosis, HCV positivity, CAH, and transaminases were significant; all the 11 patients with 5 negative prognostic factors showed an early recurrence. On the contrary, only cirrhosis was related to a late recurrence. Survival rate was significantly better in late than in early recurrence (61.9%, 27.1% and 25.7%, 4.5% at 3-5 years); a curative procedure was performed in 67.6% in group 1 and 29.3% in group 2. After a radical treatment of IR, the survival was comparable with the group of patients without recurrence.
Early and late recurrences are linked to different predictive factors. The modality of presentation of the recurrence together with the feasibility of a radical treatment are the best determinants for the prognosis.
It has been proposed that several neurohumoral factors may be involved in the genesis of vascular structural changes (remodeling or hypertrophy) frequently observed in essential hypertension. ...Therefore, in this study we investigated vascular structural alterations of subcutaneous small resistance arteries in patients with secondary forms of hypertension. The study included 70 participants11 with pheochromocytoma, 13 with primary aldosteronism, and 17 with renovascular hypertension; 13 normotensive subjects and 16 patients with essential hypertension served as controls. All subjects were submitted to a biopsy of subcutaneous fat. Small resistance arteries were dissected and mounted on a micromyograph, and media-lumen ratio, media thickness, remodeling index, and growth index were evaluated. Endothelial function was evaluated according to the dose-response curve to acetylcholine. In patients with either primary aldosteronism or renovascular hypertension, a marked increase in media-lumen ratio was observed, whereas in patients with pheochromocytoma, the extent of vascular structural alterations was similar to that observed in patients with essential hypertension. The increase in media-lumen ratio in patients with essential hypertension and with pheochromocytoma was mainly due to vascular remodeling (remodeling index, 93% to 94%), whereas in patients with renovascular hypertension, there was vascular growth (remodeling index, 70%; growth index, 53%). Patients with primary aldosteronism had an intermediate pattern compared with the other two forms of secondary hypertension. An evident impairment of endothelial function was observed in all four hypertensive groups. In conclusion, the renin-angiotensin-aldosterone system seems to be more powerful than the adrenergic system in inducing vascular growth. (Hypertension. 1996;28:785-790.)
The aim of our study was to evaluate the relationships between endothelial function, small resistance artery structure, and blood pressure in patients with primary or secondary hypertension. Sixty ...subjects were included in the study: 9 patients with pheochromocytoma, 10 with primary aldosteronism, 17 with renovascular hypertension, and 13 with essential hypertension with 11 normotensive subjects who served as controls. Clinic and 24-hour ambulatory blood pressure (ABPM) were evaluated. All subjects were submitted to a biopsy of subcutaneous fat. Small resistance arteries were dissected and mounted on a micromyograph and the media/lumen ratio was calculated. A dose-response curve to acetylcholine was performed at cumulative concentrations from 10(-9) to 10(-5) mol/L. The vasodilator response to acetylcholine was similarly impaired in the four groups of hypertensive patients (ANOVA P<.05 versus normotensive controls), without any significant difference among them. In subcutaneous small arteries of patients with either primary aldosteronism or renovascular hypertension, a marked increase in media:lumen ratio was observed, while in patients with pheochromocytoma, the extent of vascular structural alterations was similar to that observed in essential hypertension. No significant correlation between media-lumen ratio or clinic blood pressure and maximum acetylcholine-induced vasodilatation was observed. On the contrary, a significant, albeit not very close, correlation between ABPM values and maximum acetylcholine-induced vasodilatation was observed (r=34, P<.05 with 24-hour systolic blood pressure, r=0.36, P<.05 with 24-hour diastolic blood pressure). In conclusion, endothelial dysfunction seems to be independent from the degree of vascular structural alterations and from the etiology of hypertension, and it is probably more linked to the hemodynamic load.
Expression of plasminogen activators (PAs) and urokinase-type PA receptor (u-PAR) is associated with tumor growth and invasion. For in vivo human tumor tissues, there is no information on gene ...expression of PAs in hepatocellular carcinoma (HCC) or other hepatic pathophysiological conditions. In this study we examined the relative levels of u-PA, tissue-type PA (t-PA), and u-PAR mRNA expression in human HCC by reverse transcription-PCR compared with those expressed in peritumoral hepatic tissues. Twenty-five of 25 HCCs expressed u-PA mRNA, as well as 16 of 25 hepatic peritumoral tissues. However, none of the 14 cases of nontumorous liver samples (i.e., normal parenchyma, steatosis, and nonspecific reactive and chronic hepatitis) showed detectable levels of u-PA mRNA. The same samples analyzed for uPAR and t-PA mRNAs exhibited higher levels of these mRNAs in the malignant tissues compared with nontumorous ones. A strong correlation was found between the relative levels of u-PA and t-PA mRNAs detected in the tumor and in the corresponding peritumoral tissues (P < 0.001 for u-PA; P < 0.02 for t-PA). However, there was no correlation between the expression of u-PA and t-PA in HCC (P = 0.565). Furthermore, a significant inverse correlation was found between survival months of male patients and the relative level of u-PA mRNA (P < 0.05) detected at the time of biopsy, whereas no correlation was found in the case of t-PA mRNA. These results are in line with the possible differential biological role of u-PA and t-PA in the tumor etiopathogenesis and suggest that the detection of relative levels of u-PA mRNA may be a useful prognostic factor for male HCC patients.
Hepatocyte growth factor/scatter factor (HGF/SF) is one of the most important humoral mediators of liver regeneration. It is potentially related to molecular mechanisms of hepatocarcinogenesis via a ...paracrine system involving its cellular receptor, c-met. In this study, the expression patterns of HGF and c-met were evidenced by multiplex RT-PCR in different specimens of human hepatic tissues (n = 71). A significant increase of c-met mRNA expression was detected in hepatitis (P = 0.001), cirrhosis (P = 0.006), and hepatocellular carcinoma (HCC) tissue (P = 0.003) compared with normal parenchyma and steatosis. HGF mRNA expression was significantly higher only in hepatitis (P = 0.01). Over-expression of c-met mRNA and under-expression of HGF mRNA were detected in the HCCs compared with the corresponding peri-tumoral tissues. Neither HGF nor c-met expression was related to age, sex, tumor size, grading, presence of pseudocapsula, and proliferative activity of the malignant hepatocytes. A significant inverse correlation was found between c-met mRNA expression level and survival (in months) of patients (P = 0.007), as previously shown for urokinase-type plasminogen activator (u-PA) mRNA (P = 0.027). In addition, c-met mRNA expression was strictly associated with u-PA mRNA level in HCC samples (P = 0.001). These data show that a loss of balance concerning HGF, c-met, and u-PA mRNA expression occurs during hepatocarcinogenesis. Particularly, up-regulation of c-met and u-PA mRNA transcription appears to be coordinately regulated, and their levels of expression are inversely correlated with survival; they must therefore play an important role in the development and progression of human HCC and may also be relevant prognostic markers.
Background. Data on cardiac and vascular structure in secondary hypertension are generally scarce, and no data on the interrelations between cardiac mass and structural characteristics of the vessel ...wall, both in large and in small resistance arteries, are presently available.
Objectives. The aim of this study was to investigate the relation between structural changes in subcutaneous small arteries, left ventricular mass and wall thickness of the common carotid artery in patients with primary and secondary hypertension.
Methods. Seventy-four subjects were included in the study: 11 patients with pheochromocytoma, 14 with primary aldosteronism (PA), 19 with renovascular hypertension (RVH), 18 with essential hypertension (EH) and 12 normotensive (NT) control subjects. All subjects were submitted to a biopsy of subcutaneous fat. Morphologic characteristics of subcutaneous small resistance arteries (relaxed diameter <300 μm) were directly evaluated using a micromyographic technique. All subjects were submitted to calculation of left ventricular mass index (LVMI) and common carotid artery intima-media thickness (CCIMT), using ultrasound technique.
Results. The correlation coefficients between the media to lumen ratio in subcutaneous small arteries (M/L) and LVMI or between M/L and CCIMT were closer in RVH than in pheochromocytoma, EH or NT; in PA the correlation coefficients were slightly less close than those in RVH. An excess prevalence of carotid plaques in RVH was observed.
Conclusions. A close relation between small resistance artery morphology and cardiac or carotid artery structure may be observed in those hypertensive patients in whom the renin-angiotensin-aldosterone system is activated. In constrast, in NT, EH and pheochromocytoma no significant correlation between M/L and LVMI or CCIMT was observed.
Colorectal cancer is one of the most frequent causes of death in Western countries. Most patients develop metastasis traveling through the lymphatic system, and regional lymph node metastasis is ...considered a marker for dissemination, increased stage, and worse prognosis. Despite rapid advances in tumor biology, the processes that underpin lymphatic invasion and lymph node metastasis remain poorly understood. The aim of this study was to establish an easy protocol for isolation of pure tumor lymphatic endothelial cells derived from lymph nodes to study differences compared with normal endothelial cells of uninvolved tissue from the same patients. Cells were isolated with very high purity via magnetic cell sorting and express the specific lymphatic markers Prox-1 and Lyve-1. They show differences in expression of adhesion molecules, chemokines, and growth factor secretion, and capability to form capillaries when seeded on basal membrane, thereby, revealing important differences between the two cell type. These cultures may provide a promising platform for the comparative analysis of both cell types at the molecular and biological level and to optimize treatment strategies.
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