Staging of hepatocellular carcinoma: assessment of the Japanese TNM and AJCC/UICC TNM systems in a cohort of 13,772 patients in Japan

OBJECTIVE: The aims of this study were to present evidence to develop and validate the Japanese Tumor-Node-Metastasis (TNM) staging system for primary liver cancer and to compare its discriminatory ability and predictive power with those of Vauthey's simplified staging, which was adopted as the TNM staging system of the American Joint Committee on Cancer (AJCC)/International Union Against Cancer (UICC). SUMMARY BACKGROUND DATA: Among many staging systems for hepatocellular carcinoma, the Japanese TNM staging system and the AJCC/UICC staging system were developed based on a survival analysis of surgical patients. These 2 staging systems have not been compared in large series. METHODS: The Liver Cancer Study Group of Japan (LCSGJ) prospectively collected clinicopathologic data of 63,736 patients with primary liver cancer from 1995 to 2001. Among them, 13,772 patients received curative hepatic resection. Based on univariate and multivariate survival analyses, the Japanese TNM staging system was developed. The accuracy of the Japanese TNM staging system for predicting patient survival was compared with that of the AJCC/UICC staging system using the cross-validation method. RESULTS: The independent prognostic factors (relative risk; 95% confidence interval) were vascular or bile duct invasion (1.36;1.29-1.43), liver cirrhosis (1.26;1.20-1.32), diameter (< or =2 cm or >2 cm) (1.21;1.14-1.28), alpha-fetoprotein (1.20;1.15-1.25), single/multiple (1.18;1.12-1.23), liver damage (1.15;1.10-1.20), hepatic involvement (1.14;1.09-1.19), histologic differentiation (1.14;1.08-1.20), gross classification (1.13;1.08-1.18), and esophageal varices (1.07;1.02-1.13). Based on these results, 3 criteria (vascular or bile duct invasion, diameter, and single/multiple) were selected. Patients with none of these 3 factors were considered T1, and those with 1, 2, and 3 factors were T2, T3, and T4, respectively. The number of patients and 5-year survival rates for T1, T2, T3, and T4 were 2078, 70%; 6853, 58%; 3021, 41%; and 582, 24% (P < 0.0001), respectively, while those for the AJCC-T were 8457, 61% in T1, 2888, 46% in T2, and 1189, 30% in T3 (P < 0.0001). While both the LCSGJ-T and the AJCC-T had good discriminating ability, the former was significantly superior (P = 0.0007). CONCLUSIONS: Our findings support the development of LCSG stage. While both staging systems allow for the clear stratification of patients into prognostic groups, the LCSGJ staging may be more appropriate for stratifying patients with early-stage HCC.     

Prophylactic hepatic irradiation following curative resection of pancreatic cancer

Background/Purpose It is unlikely that adjuvant chemoradiotherapy applied to the pancreatic bed alone significantly improves the survival of patients with resectable pancreatic cancer. The aim of the present study was to determine whether prophylactic hepatic irradiation (PHI) improved patient outcome after the curative resection of pancreatic cancer.Methods The study population was comprised of 34 patients (PHI group) who were administered PHI after curative resection of pancreatic cancer between September 1994 and December 2003. The whole liver was irradiated with a total dose of 19.8–22.0 Gy under continuous infusion of 5-fluorouracil. The cumulative rate of liver metastasis and the survival outcomes of the PHI group were compared with those of 31 patients without PHI (non-PHI group) who underwent curative resection of pancreatic cancer.Results The planned PHI was completed for 32 of the 34 patients. Two patients developed complications that might have been PHI-related. One developed liver abscesses which were successfully managed by percutaneous drainage. The other died of liver failure without recurrence 11 months after the operation. The cumulative incidence of liver metastasis was significantly lower for the PHI group than the non-PHI group (P = 0.0455). Patients in the PHI group also survived significantly longer compared to those in the non-PHI group (P = 0.0002).Conclusions The present findings suggest that PHI is well tolerated and is a potentially effective treatment strategy after curative resection of pancreatic cancer, thereby providing the basis for a randomized controlled trial.     

Lobectomy by video-assisted thoracic surgery for lung cancer patients aged 80 years or more.

To clarify the usefulness of video-assisted lobectomy for lung cancer patient aged 80 years old or more, a retrospective study was conducted to evaluate the clinical outcome. Between 1982 and 2001, 914 patients underwent surgery for primary lung cancer at the Nippon Medical School Hospital. Among them, 32 patients underwent lobectomy, including 17 with a mean age of 82 years (range, 80 to 91 years) who underwent video-assisted lobectomy and 15 with a mean age of 82 years (range, 80 to 86 years) who underwent lobectomy by standard thoracotomy. Of these 32 patients, clinical outcome was evaluated retrospectively. Mortality was 4 (12.5%) of 32 patients consisting of 3 (20%) of 15 who underwent lobectomy by standard thoracotomy and 1 (5.9%) of 17 who underwent video-assisted lobectomy. Single variate analyses revealed that the presence of preoperative cardiopulmonary disease, 0.6 L or more of predicted postoperative forced expiratory volume in one second/m(2), 700 ml or more of blood loss, five hours or more of duration of operation and two or more of postoperative complications were considered as risk factors regarding mortality within three months postoperation. Among the patients who underwent lobectomy with mediastinal lymph node dissection, the 5-year survival rate at stage I (IA+IB) was 55.6% for patients who underwent video-assisted lobectomy and 0% for patients who underwent lobectomy by standard thoracotomy (IA=2, IB=2). Video-assisted lobectomy for lung cancer patients aged 80 years or more is considered to offer an acceptable clinical outcome. However, further observation on prognosis is necessary.     

单核细胞增强5′-脱氧氟尿苷抗结直肠癌细胞活性

目的 探讨巨噬细胞在结直肠癌化疗中的调控作用。方法 应用ELISA法分别检测结直肠癌细胞系LS174T、Clone A、Colo320、MIP101的胸苷磷酸化酶(dThdPase)蛋白含量。采用MTT分析,分别测定出氟尿嘧啶(5-FU)和5’-脱氧氟尿苷(5’-DFUR)对上述4种癌细胞的半数有效浓度(IC50)。然后把5’-DFUR加入培养基中同人血单核细胞一起培养24 h,其培养上清液2倍稀释后加入结直肠癌细胞中行MTT分析测定其IC50有无改变。同时测定单核细胞在不同浓度5’-DFUR中的存活率。结果 4种结直肠癌细胞仅LS174T检出0.5 U/mg的dThdPase蛋白,其它3种未检出。4种癌细胞对5-DFUR的IC50均明显高于5-FU(P<0.01)。同人血单核细胞一起培养后,5’-DFUR对4种癌细胞的IC50明显下降,仅相当于处理前的11.6％～34.3％(P<0.05),同时发现5’-DFUR对人血单核细胞无明显生长抑制作用。结论 被检结直肠癌细胞因缺乏dThdPase活性,不能在细胞内转化抗癌药物5’-DFUR为5-FU发挥细胞毒作用;同人血单核细胞一起培养后,5’-DFUR在单核细胞内dThdPase的催化下,可转化成5-FU并释放到培养基中发挥抗癌作用。     

Clearance of the eustachian tube under negative middle ear pressure

The influence of negative middle ear pressure on clearance function of the eustachian tube was examined in cats. In experiment 1, mucociliary clearance of a colored fluid through the eustachian tube was examined under negative middle ear pressure. The results showed that negative pressure affects mucociliary clearance only at quite high levels. In experiment 2, muscular clearance of fluid under negative middle ear pressure was investigated during electrical stimulation of the tensor veli palatini muscle. It was found that massive discharge of fluid by the muscle activity occurs only when the negative middle ear pressure was low. For massive discharge of effusion, muscular clearance is more effective than ciliary clearance. The findings suggest that it is clinically important to maintain middle ear ventilation.     

Gas Exchange Function Through the Mastoid Mucosa in Ears After Surgery

Gas exchange function through the mastoid mucosa was investigated in ears after surgery using nitrous oxide. Increase in the mastoid pressure was assessed by a micropressure sensor placed in the mastoid cavity during the second-stage revision operation performed under general anesthesia using 67% nitrous oxide, 33% oxygen, and sevoflurane on 14 ears with chronic adhesive otitis media or cholesteatoma as well as on seven ears without inflammation as controls. All seven control ears showed pressure increase in the mastoid in various degrees. In the 14 postoperative ears, nine of the 10 ears on which the mastoid mucosa had previously been able to be preserved in various degrees showed pressure increase in the mastoid, but none of the remaining four ears, which had previously had mastoidectomy, showed any pressure increase. The presence or absence of the mastoid pressure increase of those ears was also found to be correlated well with the presence or absence of mastoid aeration on computed tomography examined just before the second-stage operation. These results appear to indicate that, in ears after surgery, recovery of both the gas exchange function and aeration in the mastoid is expected only when the mastoid mucosa can be preserved even partially.     

Association between Multimorbidity and Kidney Function among Patients with Non-Dialysis-Dependent CKD: The Fukuoka Kidney Disease Registry Study

Aim: Individuals with chronic kidney disease (CKD) have a high prevalence of comorbidities, including cardiovascular disease (CVD) and its risk factors. However, epidemiological results to assess the association between multimorbidity and kidney function among the CKD population remains limited. Methods: We performed a cross-sectional analysis of the association between 23 comorbid conditions and reduced kidney function in 4,476 patients with non-dialysis-dependent CKD enrolled in a multicenter cohort in Japan. Reduced kidney function was defined as an estimated glomerular filtration rate of ≤ 60 mL/min/1.73 m². Results: The mean age of patients was 67 years (male, 56.0%). The prevalence of hypertension, diabetes mellitus, dyslipidemia, prior CVD, cancer, and bone fracture, which are the major comorbidities, was 83.3%, 28.7%, 45.9%, 23.3%, 12.7%, and 6.3%, respectively. Multivariable-adjusted analyses revealed that age, male sex, hypertension, dyslipidemia, prior CVD, body mass index, urinary protein excretion, and underlying kidney disease were independent factors associated with reduced kidney function. Importantly, the odds ratios (ORs) for reduced kidney function increased linearly as the number of major comorbid conditions increased (OR for 1–2 conditions: 2.22, 95% confidence interval [CI]: 1.65–2.97; OR for 3–4 conditions: 3.04, 95% CI: 2.12–4.37; OR for ≥ 5 conditions: 4.37, 95% CI: 1.75–10.9). The upward trend in OR was more pronounced with cardiovascular comorbidities but not significant with non-cardiovascular comorbidities. Conclusions: In conclusion, we observed an independent association between cardiovascular comorbidity and its risk factors and reduced kidney function. The results of this study highlight the importance of managing multimorbidity among patients with CKD.     

Effect of the rhizomes of Atractylodes lancea and its constituents on the delay of gastric emptying

The effect of rhizomes of Atractylodes lancea on gastric disorders, in particular, the delay in gastric emptying induced by N(G)-nitro-L-arginine in rats, was investigated. Intragastric treatment with an aqueous extract (250 mg/kg) and its lipophilic fractions (4 mg/kg) significantly improved delayed gastric emptying. The major constituents of the lipophilic fraction were two sesquiterpens, hinesol and beta-eudesmol, and four known polyacetylenic compounds, atractylodin, atractylodinol, acetylatractylodinol and 4,6,12-tetradecatriene-8,10-diyne-1,3,14-triol. The activity was found in the four polyacetylenic compounds at a similar potency, but not in the two sesquiterpens. To clarify the effect of the four polyacetylenic compounds in this extract, we attempted to evaluate the activity of atractylodin, as representative, at a dose of 0.2 mg/kg based on the total amounts (0.2 mg/250 mg aqueous extract) of the four polyacetylenic compounds. In addition, atractylodin improved the delay in gastric emptying at between 0.1 and 0.3 mg/kg in a dose-dependent manner. These results suggest that the aqueous extract improved the delayed gastric emptying, and polyacetylenic compounds contributed to its activity.     

Efficacy and Safety of Prasugrel vs Clopidogrel in Thrombotic Stroke Patients With Risk Factors for Ischemic Stroke Recurrence: A Double-blind,Phase III Study (PRASTRO-III)

Aim: To examine the efficacy and safety of prasugrel vs clopidogrel in thrombotic stroke patients at risk of ischemic stroke. Methods: This multicenter, active-controlled, randomized, double-blind, double-dummy, parallel group study enrolled thrombotic stroke patients aged ≥ 50 years at risk of ischemic stroke. Patients received prasugrel (3.75 mg/day) or clopidogrel (75 or 50 mg/day) for 24–48 weeks; other antiplatelet drugs were prohibited. The primary efficacy endpoint was the composite incidence of ischemic stroke, myocardial infarction (MI), and death from other vascular causes from the start to 1 day after treatment completion or discontinuation. Secondary efficacy endpoints included the incidences of ischemic stroke, MI, death from other vascular causes, ischemic stroke and transient ischemic attack, and stroke. Safety endpoints included bleeding events and adverse events (AEs). Results: In the prasugrel (N=118) and clopidogrel (N=112; all received 75 mg) groups, the primary efficacy endpoint composite incidence (95% confidence interval) was 6.8% (3.0%–12.9%) and 7.1% (3.1%–13.6%), respectively. The risk ratio (prasugrel/clopidogrel) was 0.949 (0.369–2.443). Secondary efficacy endpoints followed a similar trend. The combined incidences of life-threatening, major, and clinically relevant bleeding were 5.0% and 3.5% in the prasugrel and clopidogrel groups, respectively. The incidences of all bleeding events and AEs were 19.2% and 24.6% and 76.7% and 82.5% in the prasugrel and clopidogrel groups, respectively. No serious AEs were causally related to prasugrel. Conclusions: We observed a risk reduction of 5% with prasugrel vs clopidogrel, indicating comparable efficacy. There were no major safety issues for prasugrel.