Long-term outcomes of endoscopic papillary balloon dilation and endoscopic sphincterotomy for bile duct stones.

AIM: We recently reported that endoscopic papillary balloon dilation (EPBD) might suppress biliary bacterial contamination better than endoscopic sphincterotomy (EST) in patients with small bile duct stones (diameter ≤8 mm). In the present study, we evaluated immediate and long-term outcomes of endoscopic papillary balloon dilation with regard to stone size. METHODS: We allocated 474 patients alternately to the two procedures. The patients were classified according to stone diameter (≤8 mm or >8 mm) and outcomes (i.e. complete stone removal, early complications, and late complications) were compared. The predictive risk factors for late complications were also investigated. RESULTS: In patients with small stones, complete stone removal rate and early complication rate were similar between the two procedures; the incidence of pancreatitis was higher after EPBD, although the difference was not significant. Late complication rate and stone recurrence rate were significantly lower after EPBD than after EST (5.3% vs 17.3%, P = 0.009; 4.4% vs 12.7%; P = 0.048, respectively). In patients with large stones who underwent EPBD complete stone removal rate and late complication rate were lower, but the incidence of pancreatitis was higher. However, these differences were not statistically significant. Multivariate analysis showed that the increased risk of bactobilia following EPBD for large stones or EST, and the gallbladder with stones in situ were independent risk factors for late complications. CONCLUSIONS: EPBD produced significantly better long-term outcomes than EST in patients with small bile duct stones.

Methyl mercury exposure at Niigata, Japan: results of neurological examinations of 103 adults.

BACKGROUND: Large-scale poisonings caused by methyl mercury (MeHg) have occurred in Japan (Minamata in the 1950s and Niigata in the 1960s) and Iraq (in the 1970s). The current WHO neurological risk standard for adult exposure (hair level: 50 µg/g) was based partly on evidence from Niigata which did not consider any cases who were diagnosed later and/or exposed to low level of MeHg (hair mercury level less than 50 µg/g). METHODS: Early in the Niigata epidemic in June 1965 there were two extensive surveys. From these two surveys, we examined 103 adults with hair mercury measurement who consulted two medical institutions. We compared the prevalence and the distribution of neurological signs related to MeHg poisoning between exposure categories. RESULT: We found 48 subjects with neurological signs related to MeHg poisoning who had hair mercury concentration less than 50 µg/g. Among the neurological signs, sensory disturbance of the bilateral distal extremities was observed more frequently, followed by disequilibrium, hearing impairment, and ataxia, in groups with hair MeHg concentration both below 50 µg/g and over 50 µg/g. CONCLUSION: The present study suggests the possibility that exposure to MeHg at levels below the current WHO limits could cause neurologic signs, in particular, sensory disturbance.

Effects of endoscopic papillary balloon dilation and endoscopic sphincterotomy on bacterial contamination of the biliary tract.

BACKGROUND AND STUDY AIMS: Although endoscopic papillary balloon dilation (EPBD) has appeared with the expectation of better preserving sphincter of Oddi function than endoscopic sphincterotomy (EST), whether it can more effectively prevent bacterial contamination of the biliary tract than EST is controversial. To address this issue, we investigated the bacterial flora in the bile after the two procedures. PATIENTS AND METHODS: Eighty-six patients were alternately allocated to EPBD or EST. Blood-liver function tests, ultrasonography, and endoscopic retrograde cholangiopancreatography were performed 6 months and 2 years after EPBD or EST, and the bile was sampled for bacterial culture during endoscopic retrograde cholangiopancreatography. Bactobilia and late complications were prospectively compared between the two procedures. RESULTS: Overall, no significant difference was found in the incidence of bactobilia between EPBD and EST at the two examination points. Limiting stone diameter to 8 mm or less, there was a trend toward lower rate of bactobilia in the EPBD group 2 years later although the statistical significance disappeared after correction for multiple comparisons. The absence rate of late complications after EPBD was higher than that after EST, but there was no significant difference between the two procedures, both for the overall patients and for the patients with small stones. CONCLUSION: EPBD has a possibility of suppressing bacterial contamination of the biliary tract compared with EST in patients with small stones. A large, long-term follow-up, randomized, controlled trial is necessary to clarify whether this benefit of EPBD reduces late complications.

A case-control study of gallbladder cancer in hungary.

Our previous study indicated an association of chili pepper consumption with gallbladder cancer (GBC) in the presence of gallstones (GS) in Chile. We investigated whether or not a similar association was present in Hungary, where mortality from GBC is high and chili peppers are frequently consumed. In a case-control study, we compared 41 female GBC patients with GS and 30 gender and GS-matched hospital controls. Trained staff interviewed all subjects to determine socioeconomic status, family history, past history and life style habits (smoking, alcohol intake, dietary habits and elimination habits). Because mean ages differed significantly between the case and control groups, age-adjusted odds ratios (ORs) were calculated. A shorter education period (< 10 years / > or = 16 years) was indicated to be a risk factor (age-adjusted OR (95%CI): 3.2 (1.2-8.7)). In addition, the intake of Hungarian hot pepper (yes / no) was found to be significantly higher in the GBC cases than in controls (age-adjusted OR (95%CI): 8.4 (2.3-30.4)). There were no differences between the case and control groups for other variables. Multivariate logistic regression analysis retained only Hungarian hot pepper consumption as a significant independent risk factor for GBC. Its age-adjusted OR was 16.2 (95%CI: 2.1-126.2), while there were no differences associated with low education, frequent consumption of fresh fruit and vegetables, low socioeconomic status or smoking. Hungarian hot pepper consumption was identified as a risk factor for GBC by multivariate logistic regression analysis.

Effect of genetic predisposition on the risk of gallbladder cancer in Hungary.

A CYP1A1 polymorphism has been associated with an increased risk for gallbladder cancer (GBC) in Japanese women. However, genetic risk factors for GBC in Hungary, where the population has a relatively high GBC incidence, has not been well studied. We therefore tested associations between CYP1A1 T3801C, CYP1A1 Ile462Val, GSTM1deletion, and TP53 Arg72Pro and GBC in Hungary. Genomic DNA was extracted from peripheral blood of 100 controls (52 men and 48 women) and from the tissue embedded in paraffin of 43 cases (6 men and 37 women). The case-control analysis was limited to females due to a small number of males. Of 37 female cases, 21 (56.8%) were diagnosed as adenocarcinoma, and the remaining 16 (43.2%) were classified as non-adenocarcinoma. The odds ratios (ORs) for the Ile/Val genotype and the Val allele were 8.9 (95% CI: 2.9-27.4) and 4.4 (95% CI: 1.7-11.1), respectively. The occurrence of the combined variant genotypes of CYP1A1 Ile462Val and GSTM1 (37.8% vs. 8.3%) or CYP1A1 Ile462Val and TP53 Arg72Pro (24.3% vs. 0%) was significantly higher in the cases than in the controls. The Ile/Val genotype was significantly associated with an increased risk of adenocarcinoma (OR 9.2; 95% CI: 2.6-32.6) and non-adenocarcinoma (OR 8.4; 95% CI: 2.2-32.4). Additionally, the Arg/Pro genotype increased risk of non-adenocarcinoma (OR 3.8; 95% CI: 1.2-12.8). The Val allele may contribute to the development of GBC not only in Japanese but also in Hungarian women. Our results provide a rationale for further studies of genetic variation on the risk of GBC in Hungary.

Genetic changes of p53, K-ras, and microsatellite instability in gallbladder carcinoma in high-incidence areas of Japan and Hungary.

AIM: To disclose geographic differences in genetic changes involved in gallbladder carcinogenesis between two distinct high-incidence areas of Japan and Hungary. METHODS: We examined 42 cases of gallbladder carcinoma: 22 Japanese and 20 Hungarian cases. p53 mutations at exons 5 to 8 and K-ras mutations at codon 12 were tested by direct sequencing. Microsatellite instability was determined from fluorescent dye-labeled PCR amplifications of five-microsatellite markers (BAT-25, BAT-26, D2S123, D5S346, and D17S250). RESULTS: Mutations of p53 were detected in 11 of 22 Japanese cases and 6 of 18 Hungarian cases (11/22 vs 6/18, P = 0.348). Transition at CpG sites was found in none of 11 Japanese cases and 2 of 6 Hungarian cases; the difference was marginally significant (0/11 vs 2/6, P = 0.110). K-ras mutations were detected in only one of the Hungarian cases. Eight of 19 (42.1%) Japanese cases were MSI-high (presence of novel peaks in more than one of the five loci analyzed), whereas only 1 of 15 (6.7%) Hungarian cases was MSI-high (P = 0.047). CONCLUSION: It appears that the p53 mutations and MSI differ in patients with gallbladder carcinoma between two distinct high-incidence areas. Geographic variation might exist in the process of gallbladder carcinogenesis.

Changes in pancreatic cancer mortality, period patterns, and birth cohort patterns in Japan: analysis of mortality data in the period 1968-2002.

OBJECTIVES: The 5-year survival rate for pancreatic cancer is known to be lower than that for cancer at any other site in the body, and the proportion of pancreatic cancer deaths among all cancer deaths has been increasing in Japan. The aim of this study was to investigate pancreatic cancer mortality in the light of temporal and geographical trends in the 47 prefectures of the country between 1968 and 2002. METHODS: To survey the geographical aspects of pancreatic cancer mortality, we mapped the direct age-adjusted mortality rates of persons aged 40 years and older by sex in seven 5-year periods (1968-1972 to 1998-2002). We also evaluated the changes in period and birth cohort trends using estimable functions based on the age-period-cohort models in each prefecture. RESULTS: During the observation period the Hokkaido and Tohoku regions had high mortality rates for both sexes. No significant increase in period trends was observed from 1973 to 2002, but significant increases in cohort trends were observed from 1913 to 1962-in two prefectures, for males, and in four prefectures, for females. CONCLUSIONS: The results of this study reveal a combination of time trends in pancreatic cancer mortality and changes in period or birth cohort trends. The changes in cohort trends in each prefecture were more variable than the period trends. This finding probably indicates the need for further investigation of the cohort-related factors involved in the prevalence of pancreatic cancer. Further research on mortality in the 47 prefectures needs to be conducted while taking the two time effects into account.

[Descriptive epidemiologic studies on geographical clusterings of pancreatic cancer mortality and incidence--an analysis in Niigata, Japan].

OBJECTIVES: The objectives of this study were to determine the mortality for pancreatic cancer in the 47 prefectures of Japan and to reveal the geographical distribution of the mortality and incidence for pancreatic cancer in Niigata. METHODS: Standardized mortality ratio (SMR) for pancreatic cancer in the 47 prefectures from 1998 to 2002 was calculated on the basis of the census and vital statistics of Japan. The same SMR in the 36 cities and counties in Niigata from 1995 to 2002 was calculated. These SMRs were compared with that of the national population. Then, standardized incidence ratio (SIR) for pancreatic cancer in the 36 cities and counties in Niigata from 1995 to 2002 was calculated on the basis of the Niigata Cancer Registry, compared with that of the general population of Niigata. RESULTS: The SMRs for pancreatic cancer for both sexes in Hokkaido, Aomori, Akita, Miyagi and Shimane were significantly higher than that of the national population (p<0.05). The SMR for males in Niigata was significantly high, whereas that for females was near the SMR of the national population. Among the 36 cities and counties in Niigata, significantly high SMRs for both sexes were observed only in Higashikanbara county; the SMRs [95% confidence interval (CI)] were 158.4 (104.4-230.5) and 172.2 (114.4-248.9) for males and females, respectively. CONCLUSIONS: Significantly high SMRs for pancreatic cancer were observed in Hokkaido and most of the Tohoku region. A geographical clustering of pancreatic cancer in Higashikanbara county was found. Further studies are needed to clarify the determinants of the clustering.

Mental and physical effects of Tanshin funin, posting without family, on married male workers in Japan.

This paper investigates the effects of tanshin funin, a posting without family, on the health of married male workers. A prospective study using the pair-matched method was performed. One hundred and twenty-nine married male tanshin funin workers in their 40s and 50s and as many matched workers living with their family (regular workers) participated. Fewer tanshin funin workers took breakfast everyday (OR=3.3, p<0.001). Tanshin funin workers more frequently suffered from stress due to daily chores (OR=3.6, p<0.001) and from stress-related health problems, namely headache (OR=4.7, p=0.013) and gastric/duodenal ulcers (OR=8.7, p<0.001). They also developed more frequently common cold/bronchitis (OR=14.5, p<0.001). The levels of gamma-glutamyl transpeptidase for workers reluctant to work under tanshin funin and workers who spent less than two years in tanshin funin increased significantly from the fiscal year 1997 to year 2001 (46.7 to 67.5 IU/l, p<0.001, and 36.9 to 72.4 IU/l, p=0.005, respectively), although those of their matched regular workers did not show significant changes. The daily alcohol intake of reluctant tanshin funin workers (the equivalent of approximately 817 ml of beer) was higher than that of the matched regular workers (582 ml, p=0.026). In summary, abrupt changes in lifestyle and elevated mental stress were thus important effects of tanshin funin. Tanshin funin workers should be provided with health and lifestyle education programs and mental health care before and during tanshin funin. Doctors and nurses in the healthcare departments of companies should play a leading role.

Randomized controlled trial to evaluate effectiveness of exercise therapy (Takizawa Program) for frail elderly.

OBJECTIVE: Although exercise therapy intervention for frail elderly people was not of great interest in the past, it has recently drawn attention as a method to prevent and improve conditions requiring care since the enforcement of the Long-Term Care Insurance Law and the revision of the long-term care insurance system. This randomized controlled trial was performed to evaluate the effects of exercise therapy using the Takizawa Program. METHODS: In this randomized controlled trial, we evaluated the effects of exercise therapy on the frail elderly, including those who need a high level of care, in terms of two factors: the range of motion and the functional independence measure. The subjects were 145 females admitted to special nursing homes for the elderly. They were stratified according to their care levels and randomly assigned to either the exercise therapy intervention group or the control group. RESULTS: The range of motion values in the flexions of both shoulders, the right knee extension, and the dorsal flexions of both ankles significantly increased only in the exercise therapy intervention group. The functional independence measure score did not improve in the exercise therapy intervention group. CONCLUSION: Exercise therapy should be used for the frail elderly requiring a high level of care.

Effects of physical exercise on fall risk factors in elderly at home in intervention trial.

OBJECTIVE: In this study, we used an intervention approach to examine the effects of physical exercise on elderly people living at home in a rural area. METHODS: Two regions in a village were randomly assigned as the control and intervention regions. The subjects were 60 years of age or older and were able to carry out their activities of daily living independently. The numbers of subjects were 56 and 81 for the control and intervention regions, respectively. In the control region, lectures on health were provided twice. In the intervention region, instructions on ten types of physical exercise were provided six times during this three-month study. In addition, the subjects in the intervention region were instructed to do, exercises by themselves at home three days per week. The effects were compared by evaluating motor functions in maximum step length, 10-m full-power walking parameters, right knee extension torque, right hip flexion torque, and stepping time on a 40-cm staircase; data were obtained before and after the intervention. RESULTS: Analysis of covariance (ANCOVA) showed significant improvements in right maximum step length, the mean of the right and left maximum step lengths, and right hip flexion torque in the intervention region. CONCLUSION: The three-month physical exercise program improves the motor functions of the elderly.

Effects of low-dose cadmium exposure on biological examinations.

We conducted an epidemiological study to investigate the effects of low-dose cadmium (Cd) exposure on human health in a specific area of a town in Japan where low Cd concentration was detected in rice. We compared clinical findings, urinary and whole blood Cd concentrations, and indicators of renal dysfunction between the polluted area and the control area. The study employed 44 men and 54 women from the polluted area and 21 men and 29 women from the control area. In urine analysis, as indicators of Cd exposure and possible related renal dysfunction, Cd, beta(2)-microglobulin (beta(2)-MG), alpha(1)-microglobulin (alpha(1)-MG), N-acetyl-beta-D-glucosaminidase (NAG), total protein, inorganic phosphorus, lysozyme and creatinine were quantitatively measured. In blood analysis, serum IP and creatinine and whole blood Cd were measured. No case of renal dysfunction due to Cd exposure was confirmed. However, both the urinary and whole blood Cd of the polluted area were significantly higher than those of the control area for both sexes. Urinary beta(2)-MG did not differ between the two areas. For women, urinary alpha(1)-MG was significantly higher in the polluted area than in the control area. In correlation analysis, beta(2)-MG, alpha(1)-MG and NAG, were positively correlated with both of urinary and whole blood Cd for men and women in the polluted area except for between urinary beta(2)-MG and urinary Cd for men. In the control area, the sole positive correlation observed was between urinary beta(2)-MG and whole blood Cd for men. We then examined the determinants of variations of parameters in urinary and blood tests. Potential determinants were age, sex, body mass index, an indicator of smoking habits (cigarette index) and the index of estimated Cd intake from rice (Cd-rice-index). Cd-rice-index was expressed as the product of Cd concentrations in homegrown rice multiplied by daily frequency multiplied by duration (years) of residence in the polluted area. In multiple regression analysis, whole blood Cd was independently associated with Cd-rice-index, age and gender. Variations in whole blood Cd accounted for a substantial portion of the variations in urinary Cd, although they were less influential in older individuals. Whole blood Cd was the sole independent variable related to variations in urinary beta(2)-MG. Cd-rice-index accounted for a portion of the variance in urinary NAG, while age was a more powerful determinant. It was thus revealed that the consumption of homegrown rice polluted with Cd in low concentration resulted in an elevation of whole blood Cd level and consequent increase in urinary Cd level. However, it was not clearly elucidated that the excretion of urinary low-molecular microglobulins could increase significantly in response to slight elevation of Cd body load.

Elevated mortality from lung cancer associated with arsenic exposure for a limited duration.

In 1959, arsenic poisoning was detected in the town of Nakajo in Japan. The cause was exposure to inorganic arsenic in well water during 1954 to 1959. To examine the long-term effects of limited-duration arsenic exposure, we conducted mortality and survival studies for patients with chronic arsenic exposure and for control subjects from 1959 to 1992. The ratio of observed deaths to expected deaths from lung cancer was significantly high (7:0.64) for male patients. The lung cancer mortality rate was elevated markedly in subgroups with higher clinical severities of symptoms. Small cell carcinoma was specific to the exposed patients. The cumulative change of survival declined significantly in the exposed patients compared with the controls. The decline disappeared when lung cancer deaths were treated as lost to follow-up. The results showed that a 5-year period of arsenic exposure was associated with risk of lung cancer.

Endocrine disrupting chemicals in Hungarian canned foods.

The aim of this study was to clarify the worldwide residual levels of organochloride compounds, such as BHC and DDT, which were reportedly concentrated in animal tissues by biological food chains. As a part of the investigation of endocrine disrupting chemicals (EDCs), we had a chance to measure the level of these compounds in Hungarian canned foods.Seven kinds of canned foods were purchased at a market in Budapest, Hungary, and the concentrations of eighteen organochloride compounds (α-BHC; ß-BHC; γ-BHC; δ-BHC; p,p'-DDT; p,p'-DDE; p,p'-DDD; o,p'-DDT; heptachlor; heptachlor-epoxide; aldrin; dieldrin; endrin; oxychlordane; trans-chlordane; cischlordane; trans-nonachlor; and cis-nonachlor) were measured.Other than DDT and its metabolites, none of the EDCs were detected (levels <0.4 ppb). DDT and its metabolites, however, were detected in fish, meat and chicken liver pate. One of the DDT metabolites was detected quite frequently: p,p'-DDE was detected at a level of 1.8 ppb in fish soup concentrate, 2.3 ppb in Hungarian luncheon meat, 0.5 ppb in special luncheon meat, and 0.6 ppb in chicken liver pate.Of eighteen organochloride compounds examined, only DDT and its metabolites were detected in fish, animal meat, and animal liver. It is suggested that the DDT contamination in fish and meat is worldwide even after the ban of its use.

Dimetilnitrosamina y antioxidantes: cáncer vesicular experimental / Dimethylnitrosamine and antioxidants: experimental gallbladder neoplasms

Este tipo de estudio tiene especial interés para Chile dado el notable incremento de este cáncer, el cual se mantiene hasta la actualidad (1.628 muertes y tasa de 11,5 por 100.000 en 1995). La especie usada fue el hamster (Mesocricetus auratus) y un carcinógeno, la dimetil nitrosamina, fue administrado por vía oral, en una dosis establecida. Se formaron 3 grupos de 20 animales cada uno, por un tiempo que alcanza los seis meses. El primer grupo se organizó como control. El grupo control ha tenido muertes espontáneas después del primer año de vida y no ha mostrado ningún cáncer vesicular. Los otros dos grupos tienen muy poco tiempo de evolución para extraer conclusiones en relación a cáncer, pero habría un efecto protector de los antioxidantes