Critical appraisal of the clinical and pathologic predictors of survival after resection of large hepatocellular carcinoma

HYPOTHESIS: A subset of patients with hepatocellular carcinoma (HCC) with a diameter of 10 cm or larger may benefit from hepatic resection. DESIGN: Retrospective study of a multi-institutional database. SETTING: Five major hepatobiliary centers. PATIENTS: We identified 300 patients who underwent hepatic resection for HCC 10 cm or larger. MAIN OUTCOME MEASURES: Clinical and pathologic data were collected, and prognostic factors were evaluated by univariate and multivariate analyses. Patient survival was stratified according to a clinical scoring system and pathologic T classification. RESULTS: The perioperative mortality rate was 5%. At a median follow-up of 32 months, the median survival was 20.3 months, and the 5-year actuarial survival rate was 27%. Four clinical factors-alpha-fetoprotein of 1000 ng/mL or higher, multiple tumor nodules, the presence of major vascular invasion, and the presence of severe fibrosis-were significant predictors of poor survival (all P<.05). Patients were assigned a clinical score according to the following risk factors: 1, no factor; 2, one or two factors; or 3, three or four factors. On the basis of the clinical score, patients could be stratified into only 2 distinct prognostic groups: no factor (score of 1) vs 1 or more factors (score of 2 or 3) (P<.001). In contrast, when patients were stratified according to pathologic T classification, 3 distinct groups were identified: T1 vs T2 vs T3 and T4 combined (P<.001). Fifty-six percent of the patients with a clinical score of 2 and 20% of patients with a clinical score of 3 actually had T1 or T2 disease on pathologic examination. CONCLUSIONS: Patients with large HCCs should be considered for liver resection as this treatment is associated with a 5-year survival rate exceeding 25%. Clinical predictors should not be used to exclude patients from surgical resection because these factors do not reliably predict outcome.     

Pentoxyfylline in and prevention and treatment of chronic lung disease

The anti-inflammatory effects of pentoxfylline are associated with a number of clinical benefits. These include reduction in mortality in patients who have undergone bone marrow transplants or suffer peritonitis. In infants with sepsis, a reduction in mortality has also been associated with pentoxyfylline administration. The anti-inflammatory effects of pentoxyfylline, as well as its bronchodilator, diuretic and respiratory muscle stimulant effects suggest it may have a useful role in BPD. Interim analysis of a prophylactic trial suggests pentoxyfylline may reduce treatment requirements after the neonatal period and that, in established BPD, pentoxyfylline and dexamethasone may be of similar efficacy.     

Central venous catheter placement: comparison of the intravascular guidewire and the fluid column electrocardiograms

BACKGROUND AND OBJECTIVE: Placement of central venous catheters in patients is associated with several risks including endocardial lesions and dysrhythmias. Correct positioning of central venous catheters in the superior vena cava is essential for immediate use. The objective of a first study was to evaluate the signal quality of an intravascular electrocardiogram (ECG) during position control using a guidewire compared with the customary fluid column-based ECG system, and to assess its efficacy of correct placement of the central venous catheter. A second study tested if dysrhythmias can be avoided by intravascular ECG monitoring during catheter and guidewire advancement. METHODS: The jugular or subclavian vein of 40 patients undergoing heart surgery or who were being treated in the intensive care unit was cannulated. Intravascular ECGs were recorded during position control, and guidewire and water column lead were compared in the same patient with regard to the quality of the ECG reading and P-wave enhancement. In another 40 patients, the guidewire was inserted only 10 cm and the central venous catheter advanced under guidewire ECG control. Correct position of all the central venous catheters was confirmed by chest radiography. RESULTS: All central venous catheters were correctly positioned in the superior vena cava. For the same catheter position, the P-wave was significantly larger in the guidewire ECG than in the fluid column system. No changes in the quality of the ECG were detected when the guidewire was advanced or withdrawn by 1 cm relative to the catheter tip. Cardiac dysrhythmias were not seen during ECG-monitored advancement of the guidewire. CONCLUSIONS: ECG quality using a guidewire lead is superior to the water column-based system. Furthermore, it is independent from the exact position of the guidewire as related to the tip of the catheter. Using intravascular guidewire ECG during advancement can prevent induction of dysrhythmias.     

The FcgammaRIIa polymorphism in patients with chronic kidney graft rejection

The FcgammaRIIa receptors, which provide a crucial link between cellular and humoral components of the immune response, display allelic polymorphism. Individuals are homozygous for either arginine 131 (RR131) or histidine 131 (HH131) or are heterozygous for these two alleles (RH131). The HH131 genotype binds human IgG2 with high RR131 with low, and RH131 with intermediate affinity. The aim of the study was to evaluate the FcgammaRIIa polymorphism in patients with chronic kidney graft rejection. The study included 121 renal transplant recipients: 53 patients with long-term stable graft function and 68 with chronic allograft rejection. The distribution of FcgammaRIIa genotypes in patients with chronic kidney graft rejection did not differ significantly from that in patients with stable graft function. The results suggest that the FcgammaRIIa polymorphism is not an important genetic risk factor for chronic rejection of kidney allografts.     

Involvement of capsaicin-sensitive afferent nerves and cholecystokinin 2/gastrin receptors in gastroprotection and adaptation of gastric mucosa to Helicobacter pylori-lipopolysaccharide

Lipopolysaccharide (LPS) is one of the virulence factors in the Helicobacter pylori (Hp)-infected stomach, but it remains unknown whether single and prolonged pretreatment with Hp-LPS can affect the course of gastric damage induced by aspirin (ASA). We compared the effects of Hp-LPS with those induced by LPSs isolated from intestinal Bacteroides fragilis, Yersinia enterocolitica, and Campylobacter jejuni applied for 4 days on acute ASA-induced gastric lesions in rats. The area of ASA-induced gastric lesions, gastric blood flow (GBF), expression of mRNA and protein of leptin and plasma leptin, gastrin, interleukin-1beta, and tumor necrosis factor-alpha levels were examined. Single (once) or repeated (five times) i.p. injections of Hp-LPS (1 mg/kg) or intestinal LPSs failed to produce macroscopic gastric damage and did not affect the GBF when compared with vehicle. Hp-LPS injected repeatedly suppressed the gastric acid secretion, up-regulated leptin mRNA and protein, and increased plasma leptin and gastrin levels. Hp-LPS significantly reduced the ASA-induced gastric damage and the accompanying decline in the GBF, and these effects were significantly attenuated by capsaicin denervation and selective antagonism of cholecystokinin-B (CCK2) receptors by RPR-102681 [N-(metoxy-3 phenyl) N-(N-methyl N-phenyl-carbamylmethyl) carbamoylmethyl]-3 ureido]-3 phenyl]-2 propronique] but not by loxiglumide, an antagonist of CCK1 receptors. We conclude that 1) daily application of Hp-LPS enhances gastric mucosal resistance against ASA damage due to the increase of GBF and the expression and release of leptin and gastrin exerting trophic and gastroprotective effects, and 2) this enhanced resistance to ASA damage in Hp-LPS-adapted stomach is mediated by the sensory afferents and specific CCK2/gastrin receptors.     

Effects of Ginkgo biloba on alertness and chemosensory function in healthy adults

Ginkgo biloba is reported to enhance cognitive function in patients with selected neural disorders. Its effects in healthy, young adults are less well characterized. This work explored whether Ginkgo biloba could ameliorate decrements in alertness post-prandially and/or enhance chemosensory function. Both are functions that could be influenced by enhanced cerebral blood flow and neuronal metabolism, reported properties of the compound. A double-blind placebo-controlled study was conducted with 19 males and 20 females with a mean age of 23.6 +/- 5.4 years and mean weight of 70.0 +/- 1.9 kg. Participants were supplemented for 13 weeks with either Ginkgo biloba (mean dose 184.5 mg/d (range 130-234 mg/d)) or placebo and administered various alertness, performance, affective state and chemosensory tests at weeks 1, 5, 9 and 13. Participants did experience the post-prandial affective state decrement (i.e. post-lunch dip), but not the performance decrement. Performance on the chemosensory tests improved over the 13-week study. However, Ginkgo biloba was ineffective at alleviating the symptoms of the post-lunch dip or at enhancing taste and smell function.     

Effect of experimental diabetes on pharmacokinetic parameters of lidocaine and MEGX in rats

The aim of the study was to evaluate the effect of experimental diabetes on pharmacokinetic parameters of lidocaine and its metabolite monoethyl-glycylxylidide (MEGX) after a single intravenous administration in rats. The study was performed on male Wistar rats, randomized into 2 groups: group I--control animals and group II--animals with experimental diabetes induced by streptozotocin. Evaluation of lidocaine pharmacokinetics was performed 10 days after streptozotocin administration. Lidocaine concentrations were lower in rats with experimental diabetes compared with the values in the control group. In rats with diabetes, the shorter phase of distribution and faster drug elimination has been observed. During the pharmacokinetic study, the dynamic reduction of lidocaine concentration was accompanied by the increase in MEGX concentration in blood. Drug elimination rate constant (gammaz) increased by 68% in rats with experimental diabetes which had an effect on the shortening of lidocaine half-life in those animals (t1/2 by 39%) and on the increase in absolute clearance (CL) to 1.46 l/h comparing to control group (0.95 l/h), i.e. by 54%. The distribution rate constant of lidocaine (gamma1) was significantly greater in the animals with experimental diabetes (by 138%). The volume of distribution (Vd) in those animals decreased by 30% in comparison with the control group. The area under the plasma concentration-time curve (AUC) decreased by 48% in rats with experimental diabetes. The MEGX half-life (t1/2) increased from 0.34 h in the control group to 0.89 h in the rats with diabetes, i.e. by 165%. It reflects the impaired MEGX elimination in experimental diabetes. The results suggest that experimental diabetes can have an effect on lidocaine pharmacokinetics towards enhanced lidocaine elimination with accompanied increase in its metabolite (MEGX) concentration.