Hepatectomy for Hepatocellular Carcinoma in Elderly Patients Aged 75 Years or More

Background  The aim of this study was to clarify the characteristics of elderly hepatocellular carcinoma (HCC) patients aged 75 years or more who underwent hepatectomy and to clarify whether elderly patients with HCC benefit from hepatectomy. Methods  Between January 1990 and December 2006, 570 patients underwent curative hepatectomy for HCC. Elderly patients were defined as those aged 75 years or more. Clinicopathological data and outcomes after hepatectomy for 64 elderly and 502 younger patients were prospectively collected and compared. Results  The proportion of elderly patients with chronic viral infection was less than that of younger patients (p < 0.001). Cirrhotic patients in the elderly group were less than those in the younger group (p = 0.03). The elderly patients had better liver function than did the younger patients (p = 0.007) but had more advanced HCC with microscopic vascular invasion than did the younger patients (p = 0.04). There was no operative mortality in the elderly patients and there was no significant difference in postoperative complication rates and long-term survival after hepatectomy between the two groups. Conclusions  Hepatectomy for elderly patients with resectable HCC is safe and feasible. Selected elderly patients with HCC might benefit from hepatectomy. This work originated from the Department of Surgery, Division of Frontier Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.     

Subcutaneous Peroneus Longus Tendon Rupture Associated with OS Peroneum Fracture

We report a rare case of subcutaneous peroneus longus tendon rupture associated with os peroneum fracture. Three dimensional computed tomographic scan was useful to understand this disorder. We treated the patient with excision of fractured os peroneum and tenodesis of the proximal stump of the ruptured peroneus longus tendon to the lateral aspect of the calcaneus.

Key points

• In order to understand a rare case of subcutaneous peroneus longus tendon rupture associated with os peroneum fracture, three dimensional computed tomographic scan was useful.
• The patient was treated with excision of fractured os peroneum and tenodesis of the proximal stump of the ruptured peroneus longus tendon to the lateral aspect of the calcaneus.

Key words: Os peroneum, fracture, rupture, peroneus longus tendon.     

Toward quality improvement of thoracic aortic surgery: estimating volume-outcome effect from nationwide survey

Background: Although understanding the association between surgical volume and outcome has been the focus of much research, no study has yet reported the volume-outcome effect for thoracic aortic surgery. Methods: From the clinical database, we identified and analyzed 2875 procedures that took place across 36 centers between 2003 and 2005. The effect of hospital procedural volume was assessed for each outcome measure using a hierarchical mixed-effects logistic regression model. Clinical risk factors, procedural year, clinical processes, range of replacement, hospital volume and surgeon volume were set as fixed effects and sites were used as random intercepts. Results: The logistic regression model revealed that hospital thoracic aortic surgery volume was linked to statistically significant decreases in both 30-day mortality (p = 0.127: OR 0.988–0.999) and operative mortality (p = 0.022: 0.989–0.999). In addition, subgroup analysis showed that increased hospital volume was associated with reduced mortality rates in patients under 65 years of age (p = 0.038: 0.982–0.999) and in high-risk surgical candidates (p = 0.019: 0.989–0.999). Thoracic aortic surgery volume of surgeons, hospital adult cardiovascular surgery volume and surgeons adult cardiovascular surgery volume did not significantly impact these outcomes. Conclusions: In this study higher annual hospital thoracic aortic surgery volume of hospitals is associated with reduced mortality rates for thoracic aortic surgery. In Japan it is not the hospital general adult cardiovascular surgery volume, but the hospital specific thoracic aortic surgery volume that might be preferable for quality indicator of thoracic aortic surgery.     

Both Fibrous Capsule Formation and Extracapsular Penetration Are Powerful Predictors of Poor Survival in Human Hepatocellular Carcinoma: A Histological Assessment of 365 Patients in Japan

Background  A new definition of infiltration to the capsule (fc-inf) has been proposed as a novel marker for predicting the prognosis of 88 patients with hepatocellular carcinoma (HCC). The current aim was to present evidence to develop the fibrous capsule and fc-inf, from the Japanese histological findings for HCC, and to validate their biological significances and predictive power of survival in a large series. Methods  A total of 365 HCCs were divided into HCCs without the fibrous capsule (NC type; n = 135) and HCCs with the fibrous capsule (FC type; n = 230). Then, FC type was subclassified into two types: extracapsular infiltrating (EC) type (n = 125), in which cancer cells penetrated outside the fibrous capsule, and intracapsular (IC) type (n = 105), in which the infiltrating cancer cells stayed inside the fibrous capsule. Results  The proportion of less histological differentiation and portal venous invasion was higher in FC type than in NC type. The fibrous capsule came to be observed according to the increase of tumor size (P < 0.0001). FC type had significantly poorer outcome for overall survival than NC type (P = 0.0022). EC type showed more intrahepatic metastasis than IC type. The macroscopic subclassifications were significantly affected the presence of fc-inf. EC type had significantly poorer outcome for disease-free survival than IC type (P = 0.0132) and was an independent prognostic factor for disease-free survival (P = 0.0482). Conclusions  Fc-inf defined as extracapsular penetration was verified to be a novel marker for predicting prognosis, and presence of fc-inf might be predicted by tumor gross features.     

Comparison of placental transfer of local anesthetics in perfusates with different pH values in a human cotyledon model

Purpose

We aimed to investigate the placental transfer of local anesthetics in perfusates with different pH values, using a dual-perfused human cotyledon model.

Methods

The dual-perfused human cotyledon model was prepared from placentas obtained following cesarean delivery (n = 5). Protein-free solution was perfused through both maternal and fetal arteries. Four amide-type local anesthetics (mepivacaine [Mep]; lidocaine [Lid]; bupivacaine [Bup]; and ropivacaine [Rop]) were added to the maternal perfusate at 1 µg·ml^?1. Three conditions were tested (stage 1, maternal pH 7.4, fetal pH 7.4; stage 2, maternal pH 7.4, fetal pH 6.9; and stage 3, maternal pH 6.9, fetal pH 6.9). Venous blood samples were collected from the fetal circuit after stabilization. The fetal vein/maternal artery concentration ratio (F/M ratio) of the local anesthetics was used as an index of placental transfer. The concentration of human chorionic gonadotropin (hCG) in the maternal vein was measured at the end of each stage.

Results

The F/M ratios in all stages were in the order of: Mep > Lid > Bup ≒ Rop. The F/M ratios of Mep were significantly higher than those of the other local anesthetics in all stages. The F/M ratios of Lid were higher than those of Rop in stages 2 and 3. The F/M ratios of Lid and Rop were higher in stage 2 than in stage 3. However, the differences between the F/M ratios in the three stages were not as large as expected from the basic uncharged ([B]) condition and pH gap. The concentration of hCG showed a time-dependent decrease with increasing stage (stage 1, 81.0 ± 58.9 mIU·ml^?1; stage 2, 57.4 ± 31.8 mIU·ml^?1; stage 3, 32.1 ± 19.7 mIU·ml^?1).

Conclusion

Our data clearly show that it is the basic uncharged concentration that mainly determines the placental transfer of amide-type local anesthetics with protein-free perfusate. This finding suggests that Rop and Bup can be used more safely than Mep in terms of placental transfer.     

Effect of weekend 5-aminosalicylic acid (mesalazine) enema as maintenance therapy for ulcerative colitis: results from a randomized controlled study

BACKGROUND: 5-aminosalicylic acid (5-ASA) is known to be effective in the treatment of active ulcerative colitis (UC). The aim of the current study was to investigate the effect of 5-ASA enemas, as a maintenance therapy for UC, when administered twice weekly as a weekend treatment regimen, compared to daily oral 5-ASA alone. We hypothesized that the weekend enema therapy would be better tolerated by patients who worked or attended school. METHODS: Between January 2004 and August 2005, patients with UC, in whom remission of the condition had just been induced, were randomly assigned to either: the weekend 5-ASA enema group (n=11), who received 1 g 5-ASA enemas twice a week on Saturday and Sunday plus oral 5-ASA 3 g/day for 7 days, or to the daily oral 5-ASA use only group (n=13), who received only oral 5-ASA 3 g/day for 7 days. The primary endpoint of the study was defined as the incidence of relapse. The study was stopped after 24 patients had been enrolled because an interim analysis showed a significant benefit of the weekend 5-ASA enema group. RESULTS: In the weekend enema group, 2 patients (18.2%) had relapses compared with 10 (76.9%) in the oral 5-ASA only group. The multivariate hazard ratio of relapse associated with weekend 5-ASA enema, relative to the oral alone group, was 0.19 (95% confidence interval, 0.04-0.94). CONCLUSIONS: This study demonstrated the beneficial effects of adding weekend 1 g 5-ASA enema to daily 3 g oral 5-ASA as maintenance therapy for UC.     

Establishment of external quality control program for hs-CRP and three-year follow-up of the performance for precision and accuracy

AIM: We established an external quality control (QC) program for high-sensitivity C-reactive protein (hs-CRP) for a collaborative epidemiological study.METHODS: External QC was performed 3 times in 3 years to follow hs-CRP performance for precision and accuracy.RESULTS: For precision, the mean coefficient of variation (CV) of the internal QC by 9 laboratories was 2.2% and 1.9% in the 1st and 2nd tests, respectively. The mean CV of the external QC by 4 laboratories was 2.7% in the three tests. The CV of both the internal and external QC satisfied the acceptable range specified by the AHA/CDC Scientific Statement, CV < 10%. For accuracy, the mean values of the 1st external QC by 9 laboratories were set as the consensus value and the acceptable range was set to within +/- 10% from it. The mean accuracy by 9 laboratories was 0.51% in the 2nd external QC. The mean accuracy by 4 laboratories was - 0.37% in the 3rd external QC. These findings demonstrated that the initial consensus value was valid in the continued external QC, and hs-CRP was stable for 3 years.CONCLUSION: We demonstrated both the precision and accuracy of hs-CRP by an external QC program applied for 3 years in a collaborative epidemiological study.     

Polymorphisms of apolipoprotein e and methylenetetrahydrofolate reductase in the Japanese population

AIM: The aim of this study is to analyze the effect of apolipoprotein E (apo E) and methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms on serum lipid and homocysteine levels in the general Japanese population. METHODS: We analyzed the polymorphisms in individuals randomly selected from among participants of Serum Lipid Survey 2000. RESULTS: The frequency of the epsilon2, epsilon3, and epsilon4 alleles of APOE was 4.2, 85.3, and 10.5%, respectively. Individuals with the genotype epsilon4/epsilon4 had the highest total and low-density lipoprotein (LDL) cholesterol levels, while those with epsilon2/epsilon2 had the lowest. Individuals with the epsilon2/epsilon2 and epsilon2/epsilon4 genotypes had higher remnant-like particles (RLP)-cholesterol levels than those with epsilon2epsilon3, epsilon3epsilon3, and epsilon3epsilon4. There was a trend for individuals with the epsilon2/epsilon4 and epsilon2/epsilon2 genotypes to have higher triglyceride levels, although the difference was not significant. The presence of the T allele in a MTHFR polymorphism (C667T) was associated with higher homocysteine levels, which is more prominent in men than in women. CONCLUSION: Thus in our large-scale analysis we have shown that RLP-cholesterol is better associated with, APOE genotype than triglyceride and the effect of the T allele on MTHFR polymorphism (C667T) homocysteine levels is more prominent in men than in women among Japanese.     

Initial impact of drug-eluting stents on coronary artery bypass grafting

The impact of drug-eluting stents (DES) on the characteristics and operative results of patients referred for coronary artery bypass grafting (CABG) was studied. We reviewed data from isolated CABG patients 24 months before (group A, n = 134) and 24 months after (group B, n = 98) the introduction of DES for clinical use at Teikyo University Hospital in Tokyo. Group B patients were significantly older than those of group A (66 +/- 9 versus 69 +/- 9 years old). The number of diseased vessels was significantly larger in group B (2.5 +/- 0.6 versus 2.7 +/- 0.5) and left main trunk disease decreased in group B (27% versus 17%). Preoperative IABP support was more frequent in group B (9% versus 17%) and beating heart surgery was significantly more frequent in group B (26% versus 59%). The number of grafts was similar in the 2 groups (3.2 +/- 1.4 versus 3.0 +/- 1.1). The operative mortality rates were 0.7% and 4.1% in group A and B, respectively. Incomplete revascularization followed by postoperative percutaneous coronary intervention (PCI) was performed in 11% and 12%, respectively, and all the patients survived surgery. The operative mortality rates for arrested heart and beating heart surgery were 2% and 2%, respectively. In conclusion, after the introduction of DES, more clinically ill patients were referred to CABG. Combination therapy consisting of CABG and PCI (Hybrid) may be a treatment of choice in critical patients.     

Involvement of Krüippel-like factor 6 （KLF6） mutation in the development of nonpolypoid colorectal carcinoma

AIM： To examine Kruppel-like factor 6 （KLF6） mutations in nonpolypoid-type tumors and alterations of K-ras, p53, and B-raf in relation between mutation and morphologic type, particularly nonpolypoid-type colorectal carcinomas.
METHODS： Fifty-five early nonpolypoid colorectal carcinomas were analyzed. Loss of heterozygosity （LOH） of KLF6 and p53 was determined by microsatellite assay. Mutations of KLF6, K-ras, and B-raf were examined by polymerase chain reaction-single-strand conformation polymorphism followed by direct sequencing. In LOH- positive and/or mutation-positive tumors, multiple （4-7） samples in each tumor were microdissected and examined for genetic alterations, p53 expression was evaluated by immunohistochemistry. RESULTS： LOH of KLF6 and p53 was found in 14 of 29 （48.3%） and 14 of 31 （45.2%） tumors, respectively. In tO of the 14 （71.4%） KLF6 LOH-positive tumors and 9 of the 14 （64.3%） p53 LOH-positive tumors, LOH was found in all of the microdissected samples. In 1 of the tO （10.0%） KLF6 LOH-positive tumors, a single missense mutation was identified. K-ras and B-raf mutations were found in 5 of 55 （9.1%） and 6 of 55 （10.9%） tumors, respectively. However, these mutations were detected only in subsets of microdissected tumor samples.
CONCLUSION： These data suggest that KLF6 and p53 mutations are involved in the development of nonpolypoid colorectal carcinoma, whereas K-ras and B-raf mutations are not.