Risk Factor For Cancer Death Research Articles

Cancer Mortality Patterns by Birthplace and Generation Status of Mexican Latinos: The Multiethnic Cohort.

Latinos are the largest minority group in the United States. We assessed cancer mortality by birthplace and generation status of Mexican Latinos in the Multiethnic Cohort. We included 26 751 Latinos of Mexican origin and 6093 non-Latino Whites aged 45-74 years at cohort entry (1993-1996) from the California Multiethnic Cohort component. The Mexican Latinos comprised 42% first-generation Mexico-born immigrants, 42% second-generation (28% US-born with both parents Mexico-born and 14% US-born with 1 parent US-born and 1 parent Mexico-born), and 16% third-generation or more who were US-born with both parents US-born. Multivariable Cox models were used to calculate covariate adjusted hazard ratios and 95% confidence intervals for overall and site-specific cancer mortality by birthplace and generation status. All statistical tests were 2-sided. Cancer death rate was highest among the US-born with 1 parent US-born and 1 parent Mexico-born (age-adjusted rate = 471.0 per 100 000 person-years) and US-born with both parents US-born (age-adjusted rate = 469.0 per 100 000 person-years) groups. The US-born with both parents Mexico-born group had a 30% (hazard ratio = 1.30, 95% confidence interval = 1.18 to 1.44) higher risk of cancer death than the first-generation Mexico-born immigrants group, showing US birthplace was associated with an elevated cancer mortality. For cancer-specific mortality, US birthplace was positively associated with colorectal, liver and lung, and ovarian cancer (P values ranged from .04 to .005). Among US-born Mexican Latinos, generation status was not statistically significantly associated with overall cancer or site-specific cancer mortality. Our findings suggest that US birthplace is a risk factor for cancer death in Mexican Americans. Identification of the contributing factors is important to curtail patterns of increasing cancer mortality in US-born Mexican Latinos.

Abstract 9546: Cancer Therapeutics-Related Cardiac Dysfunction is Associated With High Risk of Cancer-Related Mortality in Patients Treated With Anthracycline-Containing Chemotherapy

Background: Cancer therapeutics-related cardiac dysfunction (CTRCD) is a concerning problem in anthracycline-containing chemotherapy. However, the impact of CTRCD on cancer-related mortality is remained to be elucidated. Methods: Consecutive 174 patients planned for anthracycline-containing chemotherapy were enrolled. Echocardiography and blood test were performed at baseline, 3 months, 6 months, 12 months after starting chemotherapy, and after that every 3 months until cardiotoxic chemotherapy was completed. Results: Of 174 patients, CTRCD was developed in 16 patients (CTRCD group, median onset was 8 months), and the other patients (no-CTRCD group) showed normal left ventricular ejection fraction (LVEF). CTRCD group showed higher levels of peak troponin I (0.05 [0.04-0.16] ng/ml vs. 0.02 [0.02-0.04] ng/ml, P<0.001), peak B-type natriuretic peptide (59 [26-161] pg/ml vs. 25 [15-41] pg/ml, P=0.001), and lower LVEF at 12-month (54.1±7.5% vs. 64.6±4.8%, P<0.001) compared to no-CTRCD group. When we set the cut-off value of troponin I at 0.03 ng/ml, sensitivity, specificity, and area under the curve to predict CTRCD were 88%, 72%, and 0.792, respectively. In CTRCD group, 4 patients (25%) discontinued cardiotoxic chemotherapy due to CTRCD, and 12 patients (75%) showed recovered LVEF to more than 53%. In total study subjects, no patients presented cardiac death in follow up period (median 1056 days), but 22 patients (13%) died due to cancer progression. Kaplan-Meier analysis revealed that CTRCD group showed higher cancer-related mortality compared to no-CTRCD group (figure, P<0.001). Multivariate Cox-proportional hazard analysis showed that CTRCD was an independent risk factor for cancer death (HR 4.639, 95%CI [1.691-12.730], P=0.003). Conclusion: The development of CTRCD was associated with high risk of cancer death, but not with cardiac death. Cardioprotective treatment and careful cancer monitoring are required to the patients with CTRCD.

Peripheral Blood Cytopenia and Risk of Cancer Mortality

▪Introduction:Unexplained peripheral blood cytopenia remains a challenge in clinical practice which requires sorting through an array of etiologies from transient abnormalities to premalignant conditions. Clonal hematopoiesis has established an association between cytopenia and hematologic cancer, likely caused by inflammatory responses leading to hematopoietic stress. Similar mechanisms may occur in other organ systems and lead to neoplasia as the link between inflammation and solid tumors is well known. Thus, cytopenia may represent an early marker of serious conditions, including malignancy. Using the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort study, we studied the association between cytopenia and cancer mortality.Methods:REGARDS prospectively enrolled 30,239 US black and white adults from 2003 to 2007 (41% black). Sociodemographic and medical data were obtained by phone interview, physical exam, and laboratory studies at enrollment (baseline CBC drawn after 8,000 people were recruited). Cancer death was identified via semiannual phone follow-up through 2018 to ascertain health events and linkage with Social Security Death and National Death Indexes. Cytopenia was defined as presence of 2 or more of the following: 1) hemoglobin below age, sex, and race-specific lowest 5th percentile, 2) white cell count below race-specific lowest 5th percentile, 3) platelet count below lowest 5th percentile, and 4) macrocytosis (MCV >98fL). Participants with baseline cancer, missing CBC, or lost to follow-up were excluded. Cox proportional hazards models were used to calculate hazard of cancer mortality associated with cytopenia, adjusting for demographics (Model 1), Model 1 + risk factors for cancer/anemia (Model 2), and Model 1 + socioeconomics (Model 3). Differences in the association of cytopenia and cancer death by race was tested by cross-product interaction terms and Inverse Odds Ratio Weighting (IORW) mediation analysis was conducted to study the effect of cytopenia as mediator in the race-cancer death interaction.Results:The analysis population included 19,028 participants, 62% were female and 60% were white. Median follow up was 9 years. There were 1112 (5.8%) cancer deaths and 3725 (19.6%) deaths from other causes. Cytopenia was present in 383 (2%) participants, of which 250 (65%) were white and 113 (35%) were black. Cytopenia prevalence increased by age and was higher in males (56%). Cytopenia was associated with increased risk of cancer mortality in all multivariate models adjusting for demographics (HR=1.60, 95%CI 1.16-2.21), cancer risk factors (HR=1.67, 95%CI 1.2-2.32), and socioeconomics (HR=1.58, 95%CI 1.12-2.23). Anemia and macrocytosis, but not leukopenia and thrombocytopenia, were hematologic parameters individually associated with risk of cancer death (Table 1). The 10-year cumulative incidence of cancer death was 13% for participants with baseline cytopenia vs. 6.5% for those without cytopenia (p<0.01, Figure 1). The race by cytopenia interaction term was significant with higher HR for cancer mortality in blacks compared to whites in all models: 2.01 vs 1.41, p=0.016 in model 1 (demographics), 2.12 vs 1.45, p=0.009 in model 2 (cancer risk factors), 1.82 vs 1.44, p=0.04 in model 3 (socioeconomics). Anemia and macrocytosis were individual hematologic parameters with higher HR for cancer death in blacks compared to whites and significant race by cytopenia interaction terms across all models (Table 2). Mediation analysis by IORW method showed that cytopenia was not a significant mediator in the pathway between the race and cancer death association (not shown).Discussion:In a large biracial prospective cohort, cytopenia was associated with increased risk of cancer mortality after adjusting for demographics, socioeconomics, and cancer risk factors. Cytopenia was a race-specific risk factor for cancer death affecting blacks more than whites, but not a mediator of the race and cancer death association. We conclude that 1) cytopenia is a risk factor for cancer death, with stronger association in blacks than whites, and 2) race is an effect modifier for the association of cytopenia with cancer death, but cytopenia is not a mediator of the black to white difference in cancer mortality. These results can inform further studies aimed at clarifying racial disparities in cancer death through theorized mechanisms such as clonal hematopoiesis. [Display omitted] DisclosuresGangaraju: Alexion: Consultancy; Sanofi Genzyme: Consultancy.

Trace proteinuria as a risk factor for cancer death in a general population

Growing evidence has demonstrated an association between nondialysis chronic kidney disease and cancer incidence, although the association between trace proteinuria and cancer death remains unclear. The aim of this study was to investigate the association between trace proteinuria and cancer death in a community-based population in Japan. This was a prospective cohort study of 377,202 adults who participated in the Japanese Specific Health Check and Guidance System from 2008 to 2011. Exposure was dipstick proteinuria categorized as − (negative), ± (trace), 1 + (mild), or ≥ 2 + (moderate to heavy). Outcome was cancer death based on information from the national database of death certificates. Adjusted Cox hazard regression model was used to evaluate the associations between trace proteinuria and cancer death. During median follow-up of 3.7 years, 3056 cancer deaths occurred, corresponding to overall cancer death rate of 21.7/10,000 person-years. In the fully adjusted model, risk of cancer death increased significantly in each successive category of proteinuria: hazard ratio (HR) (95% confidence interval [95% CI]) for risk of cancer death was 1.16 (1.03–1.31), 1.47 (1.27–1.70), and 1.61 (1.33–1.96) for trace, mild, and moderate to heavy proteinuria, respectively. Sensitivity analyses revealed a similar association between trace proteinuria and cancer death, and participants with trace proteinuria had greater risk of mortality from hematological cancers (HR: 1.59 [95% CI: 1.09–2.31]). Both mild to heavy and trace proteinuria were significantly associated with risk of mortality from cancer in a general population.

Competing Risks of Cancer and Non-Cancer Mortality When Accompanied by Lifestyle-Related Factors-A Prospective Cohort Study in Middle-Aged and Older Adults.

BackgroundThe study aimed to identify the association between the lifestyle-related factors and the cancer-specific, or non-cancer-specific mortality, when accompanied by a competing risk. Two statistical methods were applied, i.e., cause-specific hazard (CSH), and sub-distribution hazard ratio (SHR). Their respective key advantages, relative to the actual study design, were addressed, as was overall application potential.MethodsSource data from 4,584 residents (34.2% men), aged 45–64 years, were processed using two different families of regression models, i.e., CSH and SHR; principal focus upon the impact of lifestyle-related factors on the competing risk of cancer and non-cancer mortality. The results were presented as hazard ratios (HR) with 95% confidence intervals (95% CI).ResultsAge, smoking status, and family history of cancer were found the leading risk factors for cancer death; the risk of non-cancer death higher in the elderly, and smoking individuals. Non-cancer mortality was strongly associated with obesity and hypertension. Moderate to vigorous physical activity decreased the risk of death caused by cancer and non-cancer causes.ConclusionsSpecific, lifestyle-related factors, instrumental in increasing overall, and cancer-specific mortality, are modifiable through health-promoting, individually pursued physical activities. Regular monitoring of such health-awareness boosting pursuits seems viable in terms of public health policy making.

The ratio of serum eicosapentaenoic acid to arachidonic acid and riskof cancer death in a Japanese community: The Hisayama Study.

BackgroundWhether the intake of eicosapentaenoic acid (EPA) or arachidonic acid (AA) affects the risk of cancer remains unclear, and the association between the serum EPA:AA ratio and cancer risk has not been fully evaluated in general populations.MethodsA total of 3098 community-dwelling subjects aged ≥40 years were followed up for 9.6 years (2002–2012). The levels of the serum EPA:AA ratio were categorized into quartiles (<0.29, 0.29–0.41, 0.42–0.60, and >0.60). The risk estimates were computed using a Cox proportional hazards model. The same analyses were conducted for the serum docosahexaenoic acid to arachidonic acid (DHA:AA) ratio and individual fatty acid concentrations.ResultsDuring the follow-up period, 121 subjects died of cancer. Age- and sex-adjusted cancer mortality increased with lower serum EPA:AA ratio levels (P trend<0.05). In the multivariable-adjusted analysis, the subjects in the first quartile of the serum EPA:AA ratio had a 1.93-fold (95% confidence interval, 1.15–3.22) greater risk of cancer death than those in the fourth quartile. Lower serum EPA concentrations were marginally associated with higher cancer mortality (P trend<0.11), but the serum DHA or AA concentrations and the serum DHA:AA ratio were not (all P trend>0.37). With regard to site-specific cancers, lower serum EPA:AA ratio was associated with a higher risk of death from liver cancer. However, no such associations were detected for deaths from other cancers.ConclusionsThese findings suggest that decreased level of the serum EPA:AA ratio is a significant risk factor for cancer death in the general Japanese population.

Association between hyperinsulinemia and increased risk of cancer death in nonobese and obese people: A population-based observational study.

Obesity, metabolic syndrome and type 2 diabetes are associated with cancer‐related mortality. We assessed whether hyperinsulinemia is a risk factor for cancer death in nonobese people without diabetes. We conducted a prospective cohort study using data from the National Health and Nutrition Examination Survey 1999–2010 and followed up the participants until December 31, 2011. For the primary analysis of cancer mortality, we used Cox proportional hazard models to estimate hazard ratios (HRs) in the participants with hyperinsulinemia and those without. Hyperinsulinemia was defined as a fasting insulin level of ≥10 μU/mL. To identify causes of deaths, the International Classification of Diseases, Tenth Revision codes were used. This study included 9,778 participants aged 20 years or older without diabetes or a history of cancer: 6,718 nonobese participants (2,057 with hyperinsulinemia [30.6%]) and 3,060 obese participants (2,303 with hyperinsulinemia [75.3%]). A total of 99.9% completed follow‐up. Among all study participants, cancer mortality was significantly higher in those with hyperinsulinemia than in those without hyperinsulinemia (adjusted HR 2.04, 95% CI 1.24–3.34, p = 0.005). Similarly, among nonobese participants, multivariable analysis showed that cancer mortality was significantly higher in those with hyperinsulinemia than in those without (adjusted HR 1.89, 95% CI 1.07–3.35, p = 0.02). Considering that nonobese people with hyperinsulinemia were at higher risk of cancer mortality than those without hyperinsulinemia, improvement of hyperinsulinemia may be an important approach for preventing cancer regardless of the presence or absence of obesity.

Copy number increase of ACTN4 is a prognostic indicator in salivary gland carcinoma

Copy number increase (CNI) of ACTN4 has been associated with poor prognosis and metastatic phenotypes in various human carcinomas. To identify a novel prognostic factor for salivary gland carcinoma, we investigated the copy number of ACTN4. We evaluated DNA copy number of ACTN4 in 58 patients with salivary gland carcinoma by using fluorescent in situ hybridization (FISH). CNI of ACTN4 was recognized in 14 of 58 patients (24.1%) with salivary gland carcinoma. The cases with CNI of ACTN4 were closely associated with histological grade (P = 0.047) and vascular invasion (P = 0.033). The patients with CNI of ACTN4 had a significantly worse prognosis than the patients with normal copy number of ACTN4 (P = 0.0005 log-rank test). Univariate analysis by the Cox proportional hazards model showed that histological grade, vascular invasion, and CNI of ACTN4 were independent risk factors for cancer death. Vascular invasion (hazard ratio [HR]: 7.46; 95% confidence interval [CI]: 1.98–28.06) and CNI of ACTN4 (HR: 3.23; 95% CI: 1.08–9.68) remained as risk factors for cancer death in multivariate analysis. Thus, CNI of ACTN4 is a novel indicator for an unfavorable outcome in patients with salivary gland carcinoma.

Association Between Glucose Tolerance Level and Cancer Death in a General Japanese Population: The Hisayama Study

The authors examined the associations of glucose tolerance status and fasting and 2-hour postload glucose levels with the risk of cancer death in a 19-year follow-up study of 2,438 Japanese subjects aged 40-79 years who underwent a 75-g oral glucose tolerance test (1988-2007). During follow-up, 229 subjects died of cancer. The risk of cancer death was significantly higher in subjects with fasting plasma glucose levels of ≥5.6 mmol/L or 2-hour postload glucose levels of ≥11.1 mmol/L than in those with the lowest fasting or 2-hour postload glucose levels, after adjustment for potentially confounding factors. According to glucose tolerance status, not only diabetes but also impaired fasting glycemia and impaired glucose tolerance were significant risk factors for cancer death (for impaired fasting glycemia, multivariable-adjusted hazard ratio (HR) = 1.49 (95% confidence interval (CI): 1.05, 2.11); for impaired glucose tolerance, HR = 1.52 (95% CI: 1.05, 2.22); and for diabetes, HR = 2.10 (95% CI: 1.41, 3.12)). With regard to site-specific cancers, elevated fasting or 2-hour postload glucose levels were associated with the risks of death from stomach, liver, and lung cancer. These findings suggest that both prediabetic hyperglycemia and diabetes are significant risk factors for cancer death in the general Japanese population.

Pathology‐based risk stratification of muscle‐invasive bladder cancer patients undergoing cystectomy for persistent disease after induction chemoradiotherapy in bladder‐sparing approaches

What's known on the subject? and What does the study add? In bladder-sparing approach incorporating TURBT and chemoradiotherapy (CRT) to MIBC, patients who clinically achieve complete response to induction CRT enjoy favourable prognosis and quality of life with preserved functioning bladder, whereas those with persisting disease have poor prognosis despite salvage radical cystectomy. Risk factors for cancer death among the non-responders remain fully unknown. The current study showed that survival of the non-responders is clearly stratified into low- and high-risk groups based on pathology of cystectomy specimens; 5-yr CSS rates for low- (pTO-2pNO) and high-risk (pT3-4a or pN+) patients were 85% and 20%, respectively. To stratify patients with a clinical non-complete response (CR) after induction chemoradiotherapy (CRT) according to their risk of death from cancer, based on pathology of cystectomy specimens. From 1997 to 2009, 170 patients with cT2-4aN0M0 bladder cancer underwent transurethral resection followed by induction CRT (40 Gy with cisplatin). Clinical response was evaluated 4-6 weeks after completion of CRT. Patients who met partial cystectomy (PC) criteria underwent PC plus pelvic lymph node dissection for bladder preservation. Otherwise, radical cystectomy (RC) was recommended. PC criteria were unifocal tumours, intact bladder neck and trigone, and CR (defined as no evidence of residual disease) or minimal amounts of residual non-muscle-invasive bladder cancer after induction CRT. Pathological variables associated with cancer death were analysed in patients who underwent PC or RC using a multivariate Cox proportional hazard model. Of 170 patients, 81 (48%) achieved a CR and 62 (36%) met the PC criteria. After CRT, 122 patients (72%) ultimately underwent PC (n = 44, 26%) or RC (n = 78, 46%). The 5-year cancer-specific survival (CSS) rate was 96% for the patients with a CR and 50% for patients with non-CR (P < 0.001, median follow-up for survivors: 48 months). In the 122 patients who underwent cystectomy, pT3-4a (hazard ratio [HR] 8.3 versus pTO-2, P < 0.001) and pN+ (HR 3.0 versus pNO, P = 0.037) were identified as significant and independent risk factors among variables including pT stage, lymph node yield at cystectomy, pN stage, and Iymphovascular invasion. A similar result was obtained through analysis of a sub-cohort of 69 patients with non-CR. Patients with non-CR were stratified according to their risk factors into low- (pT0-2pN0, 5-year CSS rate 85%) and high-risk (pT3-4a or pN+, 5-year CSS rate 20%) groups. In CRT-based bladder-sparing approaches, patients with a clinical non-CR after induction CRT can be stratified into low- and high-risk groups for death from cancer based on pathology of cystectomy specimens. Patients at high risk are potential candidates for intensive adjuvant therapy including clinical trials.

1419 PATHOLOGY-BASED RISK STRATIFICATION OF MUSCLE-INVASIVE BLADDER CANCER PATIENTS UNDERGOING CYSTECTOMY FOR PERSISTENT DISEASE AFTER INDUCTION CHEMORADIATION IN BLADDER-SPARING PROTOCOLS

You have accessJournal of UrologyBladder Cancer: Invasive1 Apr 20111419 PATHOLOGY-BASED RISK STRATIFICATION OF MUSCLE-INVASIVE BLADDER CANCER PATIENTS UNDERGOING CYSTECTOMY FOR PERSISTENT DISEASE AFTER INDUCTION CHEMORADIATION IN BLADDER-SPARING PROTOCOLS Fumitaka Koga, Minato Yokoyama, Junichiro Ishioka, Noboru Numao, Kazutaka Saito, Hitoshi Masuda, Yasuhisa Fujii, Satoru Kawakami, and Kazunori Kihara Fumitaka KogaFumitaka Koga Tokyo, Japan More articles by this author , Minato YokoyamaMinato Yokoyama Tokyo, Japan More articles by this author , Junichiro IshiokaJunichiro Ishioka Tokyo, Japan More articles by this author , Noboru NumaoNoboru Numao Tokyo, Japan More articles by this author , Kazutaka SaitoKazutaka Saito Tokyo, Japan More articles by this author , Hitoshi MasudaHitoshi Masuda Tokyo, Japan More articles by this author , Yasuhisa FujiiYasuhisa Fujii Tokyo, Japan More articles by this author , Satoru KawakamiSatoru Kawakami Tokyo, Japan More articles by this author , and Kazunori KiharaKazunori Kihara Tokyo, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.1310AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Bladder-sparing protocols with TUR + chemoradiotherapy (CRT) against muscle-invasive bladder cancer (MIBC) contribute to improvement of patients′ QOL. In most protocols, patients who achieve complete response (CR) to induction CRT are subjects of bladder preservation; they enjoy good QOL and favorable prognosis while non-CR patients have poorer prognosis despite radical cystectomy (RC). Risk stratification of non-CR patients would allow personalized adjuvant therapy and eventually improve survival outcomes of bladder-sparing protocols. METHODS From 1997 to 2009, consecutive 170 cT2-4aN0M0 MIBC patients underwent TUR followed by induction CRT (40 Gy with cisplatin). 4 to 6 wk after completion of CRT, clinical response was evaluated. When patients meet partial cystectomy (PC) criteria, they undergo PC+pelvic lymph node dissection for bladder preservation. Otherwise, RC is recommended. The PC criteria include 1) intact bladder neck and trigone, 2) intravesically localized tumors, and 3) CR or minimal amounts of residual non-MIBC after induction CRT. Pathology-based risk factors for cancer death were determined in 122 patients who underwent PC (n=44) or RC (n=78). RESULTS Of 170 patients, 82 (48%) achieved clinical CR. 5-yr cancer-specific survival (CSS) rate was 96% for the CR patients vs 51% for non-CR (p<.0001, median followup 47 m). Pathological findings of 122 cystectomy specimens were: pT0/Ta,is,1/T2/T3/T4a=59/26/10/24/3; median (range) no. lymph nodes removed, 9 (0–27); pN0/N+/Nx=102/8/12; lymphovascular invasion, no/yes=91/31. Among these variables, pT3-4a (hazard ratio [HR] 8.3 vs pT0-2, p<.0001) and pN+ (HR 3.0 vs pN0, p=.037) were identified as significant and independent risk factors for cancer death. Based on these risk factors, CSS of non-CR patients was clearly stratified into high-risk (pT3-4a and/or pN+, 5-yr CSS rate 20%) and low-risk (pT0-2pN0, 5-yr CSS rate 85%). CONCLUSIONS In bladder-sparing protocols, non-CR patients after induction CRT, generally having poor prognosis despite cystectomy, are clearly stratified into favorable vs high risk group based on pathology of cystectomy specimens. Patients at high-risk (pT3-4a and/or pN+) are potential subjects for intensive adjuvant therapy including clinical trials. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e568-e569 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Fumitaka Koga Tokyo, Japan More articles by this author Minato Yokoyama Tokyo, Japan More articles by this author Junichiro Ishioka Tokyo, Japan More articles by this author Noboru Numao Tokyo, Japan More articles by this author Kazutaka Saito Tokyo, Japan More articles by this author Hitoshi Masuda Tokyo, Japan More articles by this author Yasuhisa Fujii Tokyo, Japan More articles by this author Satoru Kawakami Tokyo, Japan More articles by this author Kazunori Kihara Tokyo, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

1420 HIGH FAT DIET INDUCES INTRAPROSTATIC ASSOCIATION OF STAT-3 AND NF-&[KAPPA]B IN THE NUCLEUS-A CAUSE FOR PROSTRATE INFLAMMATION

cancer-specific survival (CSS) rate was 96% for the CR patients vs 51% for non-CR (p .0001, median followup 47 m). Pathological findings of 122 cystectomy specimens were: pT0/Ta,is,1/T2/T3/T4a 59/ 26/10/24/3; median (range) no. lymph nodes removed, 9 (0–27); pN0/ N /Nx 102/8/12; lymphovascular invasion, no/yes 91/31. Among these variables, pT3-4a (hazard ratio [HR] 8.3 vs pT0-2, p .0001) and pN (HR 3.0 vs pN0, p .037) were identified as significant and independent risk factors for cancer death. Based on these risk factors, CSS of non-CR patients was clearly stratified into high-risk (pT3-4a and/or pN , 5-yr CSS rate 20%) and low-risk (pT0-2pN0, 5-yr CSS rate 85%). CONCLUSIONS: In bladder-sparing protocols, non-CR patients after induction CRT, generally having poor prognosis despite cystectomy, are clearly stratified into favorable vs high risk group based on pathology of cystectomy specimens. Patients at high-risk (pT3-4a and/or pN ) are potential subjects for intensive adjuvant therapy including clinical trials.

Prognostic Significance of Intraperitoneal Cancer Cells in Gastric Carcinoma: Analysis of Real Time Reverse Transcriptase-Polymerase Chain Reaction after 5 Years of Followup

The presence of gastric cancer cells in the peritoneal cavity detected by cytologic examination is an important prognostic factor. A reverse transcriptase-polymerase chain reaction (RT-PCR) technique amplifying carcinoembryonic antigen mRNA was recently introduced to detect these cells more sensitively. Five-year followup was completed for 284 gastric carcinoma patients who underwent CEA RT-PCR testing. Analyses to assess the accuracy and prognostic value of this procedure were performed, along with univariate and multivariable analyses to evaluate RT-PCR as a technique with peritoneal carcinomatosis and cancer death as the outcomes variables. CEA mRNA levels exceeded the cutoff value defining a positive result in 9.5%, 29%, 66%, and 81% of patients with pT1, pT2, pT3, and pT4 stage disease, respectively. Sensitivity, specificity, positive predictive value, and negative predictive value for peritoneal carcinomatosis within 5 years of surgery were 88.5%, 81.6%, 64.5%, and 94.9%, respectively. Multivariable analysis revealed that a positive CEA mRNA result was an independent risk factor for cancer death (hazard ratio 2.82, 95% CI 1.17 -3.07) among 274 patients (10 patients with no record of nodal status were excluded from the analysis) and for peritoneal carcinomatosis (hazard ratio 1.57, 95% CI 1.07-2.29) among 242 patients who had no peritoneal deposits at operation. CEA RT-PCR is useful as a prognostic marker for increased risk of cancer death and peritoneal carcinomatosis, and might be useful in the clinical setting for selecting patients for various adjuvant treatments.

A novel classification system for patients with PTC: addition of the new variables of large (3 cm or greater) nodal metastases and reclassification during the follow-up period

Background Several factors have been proven to be useful for classifying patients with papillary thyroid carcinoma (PTC) into either low- or high-risk groups. However, the relative importance of prognostic factors, including lymph nodal metastasis, remains unclear. Methods A total of 604 patients who underwent initial surgery for PTC (diameter of tumor > 1 cm) were analyzed. The mean duration of follow-up was 10.7 years. Results By multivariate analysis for disease-specific survival, distant metastasis was the only significant risk factor (risk ratio = 65.1) for younger patients (age<50). For older patients (age≥50), distant metastasis (risk ratio = 6.7), extrathyroidal invasion (risk ratio = 2.4), and large nodal metastasis (≥3cm; risk ratio = 5.3) had relative importance. From the results, younger patients with distant metastasis and older patients with any of the 3 factors were defined as at high risk, whereas the other patients were defined as at low risk. Overall, 106 patients at high risk (18%) and 498 patients at low risk (83%) had 10-year survival rates of 69% and 99%, respectively. Only 3 patients of the low-risk group died from the disease. Among postoperative factors, recurrence within 3 years after initial surgery was the most important risk factor for cancer death. Of the high-risk group, patients with a disease-free interval of >3 years showed an excellent outcome (96% of a 10-year survival rate), similar to patients in the low-risk group. Conclusions A novel classification system, in which large nodal metastases and postoperative reclassification were added, was devised. This was useful for choosing proper therapeutic strategies, offering rational information, and determining adequate postoperative follow-up schemes for individual patients with PTC.

Relation of Serum Ascorbic Acid to Mortality Among US Adults

Purpose: To examine the relation between serum ascorbic acid (SAA), a marker of dietary intake (including supplements), and cause-specific mortality.Subjects and Methods: We analyzed data from a probability sample of 8,453 Americans age ≥30 years at baseline enrolled in the Second National Health and Nutrition Examination Survey (NHANES II), who were followed for mortality endpoints. We calculated relative hazard ratios as measures of disease association comparing the mortality rates in three biologically relevant SAA categories.Results: Participants with normal to high SAA levels had a marginally significant 21% to 25% decreased risk of fatal cardiovascular disease (CVD) (p for trend = 0.09) and a 25% to 29% decreased risk of all-cause mortality (p for trend <0.001) compared to participants with low levels. Because we determined that gender modified the association between SAA levels and cancer death, we analyzed these associations stratified by gender. Among men, normal to high SAA levels were associated with an approximately 30% decreased risk of cancer deaths, whereas such SAA levels were associated with an approximately two-fold increased risk of cancer deaths among women. This association among women persisted even after adjustment for baseline prevalent cancer and exclusion for early cancer death or exclusion for prevalent cancer.Conclusions: Low SAA levels were marginally associated with an increased risk of fatal CVD and significantly associated with an increased risk for all-cause mortality. Low SAA levels were also a risk factor for cancer death in men, but unexpectedly were associated with a decreased risk of cancer death in women. If the association between low SAA levels and all-cause mortality is causal, increasing the consumption of ascorbic acid, and thereby SAA levels, could decrease the risk of death among Americans with low ascorbic acid intakes.

Low plasma selenium as a risk factor for cancer death in middle‐aged men

In a population study, 10,000 men (aged 46-48 years) were invited to a health screening program. At follow-up, which was up to eight years later, 61 subjects had died from cancer; from 35 of these subjects, plasma samples were available that were obtained at the initial screening. These samples, together with samples from two living controls for each case, were analyzed for selenium, retinol, cholesterol, triglyceride, and a number of plasma proteins. Plasma selenium was significantly lower (p less than 0.05) in cases than in controls (means: 1.06 vs. 1.12 mumol/l). The proportion of cases increased significantly from the highest to the lowest quintile of plasma selenium, and the relative risk for cancer death was 3.8 times higher in the lowest quintile compared with the highest. Mean plasma retinol was similar in cases (2.53 mumol/l) and controls (2.56 mumol/l). Cases and controls also had similar values for plasma cholesterol, triglyceride, uric acid, apolipoprotein B, orosomucoid, prealbumin, retinol-binding protein, and beta 2-microglobulin. Apolipoprotein AI in plasma was lower among cases (p less than 0.025). Cases smoked significantly more than controls did (p less than 0.05). Data indicate that low plasma selenium was a risk factor for cancer death in middle-aged men who lived in the same area. Further studies are necessary to establish whether differences in selenium intake, selenium metabolism, or other factors related to selenium are responsible for the relations observed. At present, the available data do not justify selenium supplementation programs in the whole population.