Surgery on cirrhotic livers is fraught with complications, and many surgeons refrain from operating on patients with cirrhosis. Surgical procedures include temporal occlusion of blood flow resulting in ischemia. The mechanisms of protective strategies to prevent ischemic injury in patients with cirrhosis are not fully understood. The aim of this study was to evaluate how the cirrhotic liver tolerates an ischemic insult, whether mechanisms other than those observed in the normal liver are active, and whether intermittent clamping and preconditioning, which are known as safe surgical strategies in normal and steatotic livers, confer protection to the cirrhotic liver. We applied partial hepatic inflow occlusion to cirrhotic mice fed carbon tetrachloride according to different vascular occlusion protocols: intermittent clamping with 15 or 30 minute cycles of ischemia or ischemic preconditioning prior to 60 or 75 minutes of ischemia. Continuous ischemia (60 or 75 minutes) served as controls. The results showed that the cirrhotic liver was significantly more susceptible to 60 minutes of ischemia than the normal liver. Apoptosis was higher in the normal liver, whereas necrosis was a predominant feature in the cirrhotic liver. Both protocols of intermittent vascular occlusion and ischemic preconditioning dramatically prevented injury compared to continuous occlusion for 60 minutes. This protection was associated with reduced necrosis and apoptosis, and particularly reduced activation of the apoptotic pathway through mitochondria. In conclusion, this study extends the protective effects of ischemic preconditioning and intermittent clamping to the cirrhotic liver, highlighting a diminished apoptotic pathway with dramatic improvement in the development of necrosis. Liver Transpl 14: 980-988, 2008.
We designed this experimental study to determine the optimal cycle for intermittent inflow occlusion during liver resection. A cycle of intermittent clamping (IC) for 15 minutes of ischemia followed by reperfusion for 5 minutes during liver resection is currently the most popular protocol used by experienced liver centers. As each period of reperfusion is associated with bleeding, longer periods of clamping would be advantageous. However, the longest safe duration of successive ischemia is unknown. Three groups of mice were subjected to a total liver ischemic period for 90 minutes; 2 groups underwent IC for 15 or 30 minutes, respectively, followed by 5 minutes of reperfusion, while the control group was subjected to continuous inflow occlusion only. The degree of tissue injury was assessed using biochemical and histological markers, as well as animal survival. While serious injury was observed in the continuous clamping group, both IC groups were associated with minimal injury, including lesser degrees of apoptosis and necrosis. All animals survived in the IC groups, while all animals died following 90 minutes of continuous inflow occlusion.
Ganglioneuroma is the most differentiated tumor of neural crest origin and rarely arises in the adrenal gland. Ganglioneuroma is typically known to be benign, but very rarely can metastasize to distant sites. We report a case of a 31-year-old man with a huge adrenal mass with hepatic metastases.
Single-stranded genomic DNA of recombinant M13 phages was tested as an antisense molecule and examined for its usefulness in high-throughput functional genomics. cDNA fragments of various genes (TNF-alpha, c-myc, c-myb, cdk2 and cdk4) were independently cloned into phagemid vectors. Using the life cycle of M13 bacteriophages, large circular (LC)-molecules, antisense to their respective genes, were prepared from the culture supernatant of bacterial transformants. LC-antisense molecules exhibited enhanced stability, target specificity and no need for target-site searches. High-throughput functional genomics was then attempted with an LC-antisense library, which was generated by using a phagemid vector that incorporated a unidirectional subtracted cDNA library derived from liver cancer tissue. We identified 56 genes involved in the growth of these cells. These results indicate that an antisense sequence as a part of single-stranded LC-genomic DNA of recombinant M13 phages exhibits effective antisense activity, and may have potential for high-throughput functional genomics.
In this case of an inoperable patient with hilar cholangiocarcinoma, a successful curative resection was performed by implementing PTPE in combination with chemotherapy while waiting for sufficient recovery of liver function. Although it took approximately one year until the operation could be performed, this result was achieved by continuing the treatment without giving up.
A hospital-based case-control study was carried out to identify reproductive risk factors for breast cancer in Taegu, Korea. Four hundred and eighty-one breast cancer patients and 491 age-matched control patients examined between 1988 and 1994 were included in this study. Eleven reproductive risk factors were selected for comparison using cross tabulation and chi-square method, and univariate and multivariate logistic regression analyses were used to evaluate the odds ratios for the risk of breast cancer. The mean age of the breast cancer patients in this study was 47.5 years. Analyses demonstrated that nulliparous women had a higher risk for breast cancer (odds ratio 3.46, p = 0.03) than women with one to four live births, and women who had an abortion during their first pregnancy had a slightly increased risk (odds ratio 1.86, p < 0.01) than women who had normal deliveries, but the age at menarche and menopause did not have any influence on the risk of developing breast cancer. Although there were similarities in risk factors between Western women and women in this study, such as a higher risk for nulliparous women, two key factors were found to contrast with those of Western women. First, the mean age of breast cancer patients in this study was only 47.5 years. Second, the age of menarche and menopause of these women did not have any influence on the risk of breast cancer. any risk factors for breast cancer have been M found and many of them are recognized as established factors, at least in the Western hemisphere. Reproductive factors and the patient's age are probably among the most important risk factors. Shapiro and coworkers (1) in 1968 reported that excess of breast cancer occurred in women who had never been married, those who had no more than two pregnancies, those with an early menarche, and those with 30 or more years of menstrual activity. Then in 1970, by a seven-center collaborative study of MacMahon and co-workers (2), a late age at first full-term birth became a major reproductive risk factor for breast cancer. The relationship between age and breast cancer risk was first described by Clemmesen in 1948 (3). In the United States and most European countries, the risk of breast cancer increases rapidly with age during childbearing years and the rates continue to increase even after menopause although at a less rapid pace.Accumulated data also suggests that there are international geographic variations in the incidence and mortality rates of breast cancer (4). Due to the fact that the incidence rate of breast cancer for Korean women was reported to be 9.9 per 100,000 (5), perhaps the lowest in the world, it is reasonable to assume that risk factors might be different for Korean women than those reported for women in the Western hemisphere. We carried out a hospital-based case-control study to identify reproductive risk factors for breast cancer in Taegu, Korea. Although the cases selected here may not be representative of all Korean women, the risk factors we may
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