Is major hepatectomy with pancreatoduodenectomy justified for advanced biliary malignancy?

Background/Purpose Major hepatectomy with concomitant pancreatoduodenectomy (M-HPD) is usually indicated for the resection of diffuse bile duct cancer or advanced gallbladder cancer. This is the only procedure that can potentially cure such advanced cancers, so both a low mortality rate and long-term survival could potentially justify performing this procedure. Methods Between 1990 and 2005, the morbidity, mortality, and long-term survival of 26 patients with advanced biliary tract carcinoma 14 with diffuse bile duct cancer, 9 with advanced gallbladder cancer, and 3 with hilar bile duct cancer, who underwent hepatopancreatoduodectomy (HPD) were reviewed and analyzed. Results The overall morbidity and mortality rates were 30.8% and 0%, respectively. Postoperative infectious complications occurred in 6 patients (23.0%). The 5-year survival rate of the 14 patients with diffuse bile duct cancer who underwent HPD was 51.9%, while the 5-year survival rate in the 12 of these patients who underwent M-HPD was 61.4%. Patients with diffuse bile duct cancer without residual tumor and those without lymph node metastasis had 5-year survival rates of 68.6% and 80%, respectively. Thirty-three percent (2 of 6) of the patients who underwent M-HPD for advanced gallbladder cancer survived for more than 5 years. Conclusions Preoperative biliary drainage, portal embolization, complete external drainage of pancreatic juice, reduction of intraoperative bleeding, and prevention of bacterial colonization of bile may enable the incidence of mortality and hepatic failure to approach zero in patients who undergo HPD. Surgeons should strive for complete clearance of the tumor with a negative surgical margin to achieve long-term survival when performing M-HPD.     

Clinical and pathological features of primary carcinoma of the cystic duct

Background

According to Farrar’s criteria, a tumor restricted to the cystic duct is defined as cystic duct carcinoma, but this definition excludes advanced carcinoma originating from the cystic duct.

Patients and methods

For the purpose of this study, primary cystic duct carcinoma was defined as a tumor originating from the cystic duct. We investigated the clinicopathological features of 15 cystic duct carcinomas, including 13 that did not fit Farrar’s criteria, and compared them with those of 52 cases of gallbladder carcinoma and 161 cases of extrahepatic bile duct carcinoma.

Results

The incidence of primary cystic duct carcinoma was 6.6% among all malignant biliary tumors. The main symptom was jaundice in 67% of cases. The operative procedures employed ranged from cholecystectomy to hepatopancreatoduodenectomy. The cases of cystic duct carcinoma and bile duct carcinoma showed a high frequency of perineural infiltration. The overall 5-year survival rate of the 15 patients was 40%.

Conclusion

Patients with advanced cystic duct carcinoma show a high frequency of jaundice and perineural infiltration. Our data suggest that cystic duct carcinoma may be considered a distinct subgroup of gallbladder carcinoma. Radical surgery is necessary for potentially curative resection in patients with advanced cystic duct carcinoma.     

Glucocorticoid regulation of 24-hour oscillation in interferon receptor gene expression in mouse liver

Although the antiviral effect of interferon (IFN) varies depending on 24-h oscillation in the expression of its specific receptor, the mechanism of oscillation remains to be clarified. Here we report that oscillation in the expression of the IFN receptor gene (IFN-alpha/beta R1) in mouse liver is caused by the endogenous rhythm of glucocorticoid secretion. Brief exposure of mouse hepatic cells (Hepa 1-6) to corticosterone (CORT) resulted in a significant decrease in mRNA levels of IFN-alpha/beta R1. The CORT-induced decrease in IFN-alpha/beta R1 mRNA levels was reversed by pretreating the cells with RU486, a glucocorticoid receptor antagonist. The mRNA levels of IFN-alpha/beta R1 gene in the liver of adrenalectomized mice were consistently increased throughout the day. However, a single administration of CORT to adrenalectomized mice significantly decreased the mRNA levels of IFN-alpha/beta R1 in the liver. Furthermore, the rhythmic phase of IFN-alpha/beta R1 expression was modulated after the alteration of rhythmicity in glucocorticoid secretion, which was induced by restricted daily feeding. As a consequence, under manipulation of the feeding schedule, 2'-5' oligoadenylate synthase activities, as an index of antiviral effect, in plasma and liver at 24 h after IFN-alpha injection also varied depending on the alteration of glucocorticoid secretion rhythm. These results suggest that the endogenous rhythm of glucocorticoid secretion is involved in the circadian regulation of IFN-alpha/beta R1 expression in mouse liver. Our findings also support the notion that monitoring the 24-h variation in IFN receptor function is useful for selecting the most appropriate time of day to administer IFN.     

Prognostic value of B-type natriuretic peptide and its amino-terminal proBNP fragment for cardiovascular events with stratification by renal function

BackgroundBrain natriuretic peptide (BNP) and amino-terminal proBNP (NT-proBNP) are useful biomarkers for diagnosis and prediction of prognosis. Both of these peptides are elevated in patients with chronic kidney disease (CKD), but there is no evidence as to which peptide is the more suitable biomarker in patients with severe renal dysfunction.Methods and resultsThis retrospective cohort study evaluated patients with cardiovascular diseases (64.9 ± 11.7 years, mean ± SD). The end points were all-cause death and a composite end point of all-cause death, nonfatal myocardial infarction, nonfatal stroke, hospitalization for severe heart failure, and initiation of hemodialysis. Baseline plasma BNP and NT-proBNP levels, expressed as log-transformed data, were closely correlated in patients with CKD stages 1–3 (n = 998) (r² = 0.870, p < 0.001), whereas for CKD stages 4–5 (n = 85) there was a significant but weaker correlation (r² = 0.209, p < 0.001). During follow-up periods (51.3 ± 0.4 months), 132 patients died and 202 patients reached the composite end point. The area under the receiver operating characteristic curve (AUROC) for BNP and NT-proBNP were similar for CKD stages 1–3. However, for CKD stages 4–5, the AUC for mortality for BNP was 0.713 and that for NT-proBNP was 0.760, while the AUC for the composite end point for BNP was 0.666 and that for NT-proBNP was 0.720.ConclusionsBoth BNP and NT-proBNP are useful biomarkers for mortality and cardiovascular events, but NT-proBNP may be superior to BNP for CKD stages 4–5.     

Antigenicity of sulfanilamide and its metabolites using fluorescent-labelled compounds

In order to clarify the onset mechanisms of drug-induced allergies, three fluorescent-labelled compounds were synthesized by subjecting sulfanilamide (SA), a base compound for sulfonamides, and its active metabolites, i.e. sulfanilamide hydroxylamine and sulfanilamide nitroso, to dansylation using dansylchloride. In other words, 5-dimethylamino-N-(4-aminobenzyl)-naphthalenesulfonamide (DNS-4ABA), 5-dimethylamino-N-(4-hydroxylaminobenzyl)-1-naphthalenesulfonamide (DNS-4HABA) and 5-dimethylamino-N-(4-nitrosobenzyl)-1-naphthalenesulfonamide (DNS-4NSBA) were synthesized as model haptens. When analysed by HPLC, a conjugate of DNS-4HABA and glutathione (GSH) with nucleophilic amino acids had two peaks (P-1 and P-2). FAB-MS and ¹H-NMR revealed that the DNS-4HABA-GSH conjugate consisted of sulphinamide and semimercaptal. The reactivity of GSH to DNS-4ABA, DNS-4HABA and DNS-4NSBA was quantified by HPLC using an oxidization system (horseradish peroxidase/H₂O₂). The results show that production of DNS-4NSBA-GSH-conjugate was four to eight times higher than that of DNS-4HABA-GSH conjugate, but that DNS-4ABA did not bind with GSH. Skin reactions were assessed using guinea pigs, and strong delayed erythema was seen with DNS-4NSBA, which bound most strongly with GSH, whereas weak delayed erythema was seen with DNS-4ABA, which did not bind with GSH. This suggests a correlation between GSH conjugate production and skin reactions. DNS-4HABA enzymatically bound with proteins in rat and guinea pig liver cytosol and microsomal fractions. The proteins that bound to DNS-4HABA were purified by HPLC and then subjected to N-terminal amino acid analysis. Ubiquitin (10?kDa) and fatty acid binding protein (30?kDa) were detected in the rat liver cytosol fraction; retinol-dehydrogenase (35?kDa) in the rat microsomal fraction; and glutathione-S-transferase B (mμ) (25?kDa) in the guinea pig liver cytosol fraction. When DNS-4HABA or DNS-4NSBA binds to proteins that play important roles in the body, unexpected adverse reactions may occur. Furthermore, by utilizing our technique using model compounds, it may be possible to identify the carrier proteins of various compounds, including pharmaceutical agents.     

Effects of rotation on measurement of lower limb alignment for knee osteotomy.

The purposes of this study were to clarify the effects of rotation on two-dimensional measurement of lower limb alignment for knee osteotomy using a three-dimensional method and to determine whether this 3-D simulation method could help with planning of knee osteotomy. We developed computer software to calculate femorotibial angle (FTA) and hip-knee-ankle angle (HKA) and simulate knee osteotomy from a CT-based 3-D bone model of the lower limb. Lower limb rotation on anteroposterior long-standing radiographs was measured by superimposing the 3-D bone models. Changes in alignment with limb rotation were calculated using the software. FTA after virtual closed-wedged osteotomy was measured for a hypothetical case of a rotation error of the osteotomy plane in reattaching the proximal cutting surface to the distal cutting surface. For 31 varus knees in 20 patients with medial compartment arthritis, the mean rotation angle, relative to the epicondylar axis, with variable limb position was 7.4 +/- 3.9 degrees of internal rotation (mean +/- SD), ranging from 8 degrees of external rotation to 14 degrees of internal rotation; the mean changes in FTA and HKA were 3.5 +/- 2.2 degrees (range, 0.4-8.6) and 1.6 +/- 1.3 degrees (range, 0.2-4.9), respectively. The FTA "flexion angle" (lateral view alignment from neutral AP) and the absolute HKA "flexion angle" correlated with the change in FTA and HKA with limb rotation, respectively (FTA, R = 0.999; HKA, R = 0.993). The mean change in FTA after virtual closed-wedged osteotomy was 3.2 degrees for internal and external 10 degrees rotation errors in reattaching the osteotomy plane. Rotation may affect measurement of lower limb alignment for knee osteotomy, and 3-D methods are preferable for surgical planning.     

Isolation of human chromosome 21-specific cosmids and their uses in mapping of cosmid contigs on chromosomal subregions

Summary A cosmid library of 3×10⁵ clones has been constructed from a human x hamster hybrid cell line, 153E9a3, which contains human chromosome 21 (HC21) as the only human chromosome. From 56,500 clones of this library, 229 HC21-specific cosmids have been isolated by their hybridization to total human DNA and by their failure to hybridize to total Chinese hamster DNA. The cosmids isolated were then characterized, of these, 28 cosmids (12.2% of those tested) containedNot1 site(s), and 41 cosmids were localized on the eight subregions of HC21 by differential hybridization withAlu-PCR products obtained from a hybrid mapping panel. The cosmids localized were further integrated into the existing contigs using the end-specific probes of the clone insert. Therefore, they provided useful anchor points for contig mapping and walking.