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.     

Lymphocyte drug sensitivity is useful for prediction of the antiproteinuric effect and relapse rate in cyclosporine treatment for frequent-relapse minimal change nephrotic syndrome

BACKGROUND/AIMS: The therapeutic effect of cyclosporine A (CsA) in combination with steroids varies greatly for frequent-relapse minimal change nephrotic syndrome (FRMCNS). The association between the sensitivity of peripheral blood lymphocytes (PBLs) to CsA in vitro and the therapeutic effect of CsA in FRMCNS were investigated. METHODS: The sensitivity of PBLs in vitro and the therapeutic effect of CsA in 23 FRMCNS patients were compared. The length of time to complete remission (CR) and the number of relapses were compared using the 50% inhibitory concentration (IC(50)) of CsA in the presence of a T-cell mitogen. RESULTS: FRMCNS patients were divided into 2 groups: a low sensitivity group with an IC(50) of >14.8 ng/ml (GII, n = 10), and a high sensitivity group with an IC(50) of <14.8 ng/ml (GI, n = 13). Comparison of the length of time to CR between the 2 groups showed that GI reached CR earlier than GII (p < 0.01). GI had significantly fewer relapses than GII when CsA was administered for 12 months or longer (p < 0.01). CONCLUSION: Lymphocyte sensitivity to CsA has the potential to be an important clinical indicator of the antiproteinuric effect and relapse rate in FRMCNS.     

Induction of 11beta-hydroxysteroid dehydrogenase type 2 and hyperaldosteronism are essential for enhanced sodium absorption after total colectomy in rats

BACKGROUND: Patients who undergo total colectomy with ileopouch anal reconstruction often have persistent diarrhea and frequent bowel movements. Analysis of the intestinal adaptation after total colectomy may lead to developing novel therapies for postoperative diarrhea. METHODS: Sprague-Dawley rats underwent total colectomy with ileoanal reconstruction and were sacrificed 4 and 8 weeks later. Mucosal response to aldosterone was evaluated with the use of ileal mucosa in an Ussing chamber by measuring short circuit current after in vitro stimulation with aldosterone. We investigated the expression of 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD 2) in intestinal epithelial cells. To examine the role of hyperaldosteronism, we also evaluated rats treated with a sodium-deficient diet or subcutaneous aldosterone infusion. RESULTS: Aldosterone levels increased 80-fold after total colectomy. A comparable amount of aldosterone dramatically increased aldosterone-mediated, amiloride-sensitive short circuit current in the mucosa from colectomized rats, but not in control rats. We measured an increase in 11beta-HSD 2 messenger RNA and protein in the distal ileum from colectomized rats. Circulating aldosterone appears to be essential for these functional and molecular changes because similar results were obtained by using the mucosa from both dietary sodium-depleted and aldosterone-infused rats. CONCLUSIONS: Induction of 11beta-HSD 2 is essential for enhanced mineralocorticoid action in the remnant ileum after total colectomy in rats.     

Protein C Sapporo (protein C Glu 25 --> Lys): a heterozygous missense mutation in the Gla domain provides new insight into the interaction between protein C and endothelial protein C receptor

Interaction of the gamma-carboxyglutamic acid (Gla) domain of protein C with endothelial protein C receptor (EPCR) is a critical step for efficient activation of protein C, though interactions by mutants in the Gla domain of protein C with EPCR have been rarely evaluated. We identified a 44-year-old Japanese woman with a history of recurrent thromboembolism as an inherited missense mutation, the first such case reported in Japan, which involved a protein C Gla 25 mutation. Total protein C antigen and Gla protein C antigen levels in the proband were normal. Protein C activity measured with an anticoagulant assay was reduced, whereas that measured with an amidolytic assay was normal. She was therefore phenotypically diagnosed as type IIb protein C deficiency. Direct sequencing of the PCR fragments revealed a heterozygous G to A transition at nucleotide position 1462 in exon 3, which predicted an amino acid substitution of Glu 25 by Lys. Her mother and one son were also heterozygous for this mutation. A molecular dynamics simulation of Gla 25-->Lys/EPCR complex in water suggested that the affinity between the molecules was decreased compared to the wild type Gla domain/EPCR complex. Since Gla 25 has been shown to play an important role in protein C function, not only in membrane phospholipid binding but also in binding to EPCR, our findings provide new insight into the mechanism by which the Glu 25-->Lys mutation induces type IIb protein C deficiency in individuals.     

Differential regulation of proopiomelanocortin (POMC) mRNA expression in hypothalamus and anterior pituitary following repeated cyanamide with ethanol administration

BACKGROUND/AIM: We have investigated proopiomelanocortin (POMC) mRNA expression in the arcuate nucleus of the hypothalamus (ARC) and the anterior lobe of the pituitary (AL) following repeated cyanamide-ethanol reaction (CER). METHODS: Adult male Sprague-Dawley rats (250-290 gr) were housed in a temperature and humidity controlled environment with free access to food and water. Four experimental groups were used as follows: saline (as control), cyanamide alone, ethanol alone and ethanol with cyanamide. The animals recived daily intraperitoneal injections (i.p.) of cyanamide (10 mg/kg, 60 min before ethanol dosing) with or without ethanol (1g/kg) for 5 consecutive days, and were sacrificed 60 min after the last dosing of ethanol. The results were presented as the mean +/- SEM for each group. All groups within each deta set were compared by one-way ANOVA followed by Fisher PLSD test for multiple comparisons. A value of p < 0.05 was considered significant. RESULTS: The POMC mRNA levels in ARC were significantly decreased with cyanamide compared to the control and ethanol alone (p < 0.05 and p < 0.05 respectively), but increased in AL following repeated CER. CONCLUSION: We speculate that this differential regulation of POMC mRNA expression may be partially involved in the preventive effects on alcohol intake in response to CER.     

Arteriovenous malformation of the jejunum detected by arterial-phase enhanced helical CT, a case report

This is a report on a case of arteriovenous malformation of the jejunum, which is a relatively rare occurrence that can be detected by helical computed tomography (helical CT). The patient was a 63-year-old man who was admitted to our hospital because of a tarry stool. He developed hypotension as a result of losing a large amount of bright-red blood through rectal bleeding and was given fluids and blood transfusions. Subsequently, a helical CT scan was performed at 10-mm slice thickness. A small high-density area in the jejunum was identified on the arterial phase, which was scanned 30 sec after an intravenous infusion of 100 mL of iopamidol at a rate 2.5 mL/sec. An emergency operation, based on the diagnosis of bleeding from the jejunum, was performed because the patient had developed hypotension once again. A small, elevated lesion, which coincided with the high-density area detected by helical CT, was found in the jejunum. A segmental resection and end-to-end anastomosis were done. The pathological diagnosis revealed an arteriovenous malformation of the jejunum. In conclusion, helical CT may be an effective noninvasive method for detecting the cause and site of gastrointestinal bleeding.     

Anesthetic management for non-cardiac operation with transesophageal echocardiography in a patient with left atrial myxoma

A 68-year-old female with left atrial myxoma underwent osteosynthesis of the night tibia. During the operation we observed the motion of the tumor continuously by transesophageal echocardiography (TEE). The operation was finished successfully without any cardiovascular complications. We think that TEE was useful for observation of left atrial myxoma during this non-cardiac surgery.     

Degradation of pre-beta-high density lipoproteins and their binding activity to human blood monocytes

We have previously reported that high density lipoprotein3 (HDL3), apolipoprotein A-I (apoA-I) rich lipoprotein, binds specifically to the surface of human blood monocytes. Pre-beta-HDL with a pre-beta mobility on agarose gels is an apoA-I (MW 28 kDa)-rich and a lipid-poor lipoprotein. In the present study, we found that pre-beta-HDL purified by ion-exchange chromatography was susceptible to degradation if isolated in the absence of anti-proteases, resulting in the smaller lyso-pre-beta-HDL. The mass of lyso-pre-beta-HDL was confirmed using a delayed extraction matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (DE-MALDI-TOF MS), which showed a fragment of approximately 22,378.9 Da. We further investigated limited proteolysis of apo A-I purified from human plasma HDL with various proteases, and cleavage appeared to be limited to the C-terminal end of apo A-I (amino acids 188-223). The ability of pre-beta-HDL and lyso-pre-beta-HDL to compete for HDL binding to monocytes was determined using a flow cytometry-based assay. Pre-beta-HDL competed efficiently for binding whereas lyso-pre-beta-HDL was significantly less effective. The data may indicate that the binding sites on monocytes specifically recognize apoA-I. We suggest that limited proteolysis around amino acids 188-223 of apo A-I may affect lipid binding, which may in turn affect HDL structure and function.