• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.4
• /
• pp.1811-1815
• /
• 2014

Background: In clinical trials with no upper age limit, the proportion of older patients is usually small, probably reflecting the more conservative approach adopted by clinicians when treating the elderly. An exploratory analysis of elderly patients in the RECORD-1 Trial showed that patients ${\geq}$ 65 y.o. had superior median PFS than overall RECORD-1 population (5.4 months and 4.9 months, respectively). We investigated the efficacy, relative benefit and safety of Everolimus (EVE) as sequential therapy after failure of VEGFr-TKI therapy for older patients with metastatic renal cell cancer (mRCC), in daily practice. Materials and Methods: 172 consecutive IRB approved patients with mRCC (median age 65, M:F 135/37, 78% clear cell) who received salvage EVE at 39 tertiary institutions between October 2009 and August 2011 were included in this analysis. Some 31% had progressed on sunitinib, 22% on sorafenib, 1% on axitinib, 41% on sequential therapy, and 5% had received other therapy. Patients with brain metastases were not included and 95% of the patients had a ECOG (Eastern Cooperative Oncology Group) performance status (PS) of 0 or 1. Previous radiotherapy was an exclusion criterion, but prior chemotherapy was permitted. Adequate organ function and hematologic parameters were mandatory. EVE administration was approved by the institutional review board at each participating institution and signed informed consent was obtained from all patients. Results: Median time of the whole cohort to last follow-up was 3.5 months (range 0.4-15.2 months). Forty four percent were continuing to take EVE at last followup. There were 86 (50%) patients ${\geq}$ 65 y.o. and 86 (50%) <65 y.o. The percentage of patients who showed PR/SD was higher in the older group than in the younger one (5.9%/61.2% vs 1.2%/46.5%, respectively). Median survival of older patients was also significantly longer (3.5 +/- 0.31 vs 3.1 +/- 0.34, hazard ratio=0.45, CI; 0.255-0.802). Analysis using Cox regression model adjusted for gender, PS, number of metastases, site of metastases, histology, smoking history and age detected an association between age and PFS (p=0.011). The frequency of adverse events in elderly patients treated with EVE was no greater than that in younger patients, although such toxicity may have had a greater impact on their quality of life. Conclusions: Older patients should not generally be excluded from accepted therapies (mTOR inhibitors after failure of VEGFr-TKI therapy) for mRCC.

• Tuberculosis and Respiratory Diseases
• /
• v.49 no.4
• /
• pp.453-465
• /
• 2000

Background : Lung carcinogenesis is a multistage process involving alterations in multiple genes and diverse pathway. Mutational activation of oncogenes and inactivation of tumor suppressor genes, and subsequent increased genetic instability are the major genetic events. The p53 gene and FHIT gene as tumor suppressor genes contribute to the pathogenesis of lung cancer, evidenced by mutation, microsatellite instability(MI) and loss of heterozygosity(LOH). Methods : We analysed genetic mutations of p53 and FHIT gene in 29 surgical specimens of nonsmall cell lung cancer using PCR-single strand conformation polymorphism, DNA sequencing and RT-PCR. MI and LOH were analyzed in loci of D3S1285, D9S171, and TP53. Results : In 2 cases, point mutation of p53 gene was observed on exon 5. MI of 3 times and LOH of 14 times were observed in at least one locus. In terms of the location of microsatellite, D3S1285 as a marker of FH1T was observed in 5 cases out of 26 specimens; D9S171 as a marker of p16 in 5 out of 17; and TP53 as a marker of p53 in 7 out of 27. In view of histologic type, squamous cell carcinoma presented higher frequency of microsatellite alteration, compared to others. Mutation of FHIT gene was observed in 11 cases and 6 cases of those were point mutation as a silent substitution on exon 8. FHIT mRNA expression exhibited deletion on exon 6 to 9 in 4 cases among 15 specimens, presenting beta-actin normally. Conclusion : Our results show comparable frequency of genetic alteration in nonsmall cell lung cancer to previous studies of Western countries. Microsatellite analysis might have a role as a tumor marker especially in squamous cell carcinoma. Understanding molecular abnormalities involved in the pathogenesis could potentially lead to prevention, earlier diagnosis and the development of novel investigational approaches to the treatment of lung cancer.

• Clinical and Experimental Pediatrics
• /
• v.51 no.11
• /
• pp.1158-1164
• /
• 2008

Purpose : To investigate the discriminative ability of pediatric index of mortality 2 (PIM2) and pediatric risk of mortality III (PRISM III) in predicting mortality in children admitted into the intensive care unit (ICU). Methods : We retrospectively analyzed variables of PIM2 and PRISM III based on medical records with children cared for in a single hospital ICU from January 2003 to December 2007. Exclusions were children who died within 2 h of admission into ICU or hopeless discharge. We used Students t test and ANOVA for general characteristics and for correlation between survivors and non-survivors for variables of PIM2 and PRISM III. In addition, we performed multiple logistic regression analysis for Hosmer-Lemeshow goodness-of-fit, receiver operating characteristic curve (ROC) for discrimination, and calculated standardized mortality ratio (SMR) for estimation of prediction. Results : We collected 193 medical records but analyzed 190 events because three children died within 2 h of ICU admission. The variables of PIM2 correlated with survival, except for the presence of post-procedure and low risk. In PRISM III, there was a significant correlation for cardiovascular/neurologic signs, arterial blood gas analysis but not for biochemical and hematologic data. Discriminatory performance by ROC showed an area under the curve 0.858 (95% confidence interval; 0.779-0.938) for PIM2, 0.798 (95% CI; 0.686-0.891) for PRISM III, respectively. Further, SMR was calculated approximately as 1 for the 2 systems, and multiple logistic regression analysis showed ${\chi}^2(13)=14.986$, P=0.308 for PIM2, ${\chi}^2(13)=12.899$, P=0.456 for PRISM III in Hosmer-Lemeshow goodness-of-fit. However, PIM2 was significant for PRISM III in the likelihood ratio test (${\chi}^2(4)=55.3$, P<0.01). Conclusion : We identified two acceptable scoring systems (PRISM III, PIM2) for the prediction of mortality in children admitted into the ICU. PIM2 was more accurate and had a better fit than PRISM III on the model tested.

• Journal of Chest Surgery
• /
• v.31 no.4
• /
• pp.346-352
• /
• 1998

Rheumatic valvulitis produces at least three distinct pathologic changes, the degree varying widely among the patients: fusion of the valve leaflets at the commissures; fusion and shortening of chordae tendinae: and fibrosis of the leaflets with subsequent stiffening, contraction and calcification. The most extensive changes usually are seen in patients with recurrent attacks of rheumatic fever. We studied on outcome of the surgical treatments of rheumatic valvular diseases that have been experienced for 12 years since 1982 at Pusan National University Hospital. The diagnoses were made by rheumatic fever history, echocardiographic findings, gross operative findings and microscopic findings. Total 502 patients were performed surgery for valvular heart diseases and 440 patients of rheumatic origin have bene analysed. There were more female than male patients as 1.3:1, and the mean age was 37.8 years old. 96.3% of them affected to the mitral valve, 19.8% to aortic valve, 16.3% affected to the tricuspid valve. Most of them underwent valve replacement, and valve repair was done in 3.9% of patients. There were 36 hospital deaths(8.2%) mainly from low cardiac output syndrome, and 15 late deaths equally due to embolism and hemorrhage. Follow up was 90.1% completed(2890 patient- year). Linealized rates of late complication events are follows : thromboembolism 1.3% per patient year; anticoagulant related hemorrhage 0.8% per patient year. Overall actuarial survival including hospital mortality was 92.7＋/-2.9% in 1 year, 88.0＋/-4.5% in 5 year, 82.3＋/-7.7% in 10 year. We conclude that the rheumatic disease is still the most frequent and the most important cause of heart valve disease. So more intensive study is needed in spite of the abrupt decreasing rate of rheumatic fever in U.S.A. and other industrial country.